PMID- 2904066 TI - Anti-neutrophil cytoplasmic antibody assay in diagnosis of recurrent subglottic stenosis. PMID- 2904067 TI - Prolonged breastfeeding. PMID- 2904068 TI - Immunosuppression for membranous nephropathy. PMID- 2904069 TI - Antenatal screening for Down syndrome. PMID- 2904070 TI - Coronary care: the next step. PMID- 2904071 TI - Parenteral citric acid for aluminium intoxication. PMID- 2904072 TI - Fetal obstructive uropathy [corrected]. PMID- 2904073 TI - HIV and orogenital transmission. PMID- 2904074 TI - AIDS: who to treat? PMID- 2904075 TI - Blastocystis hominis infection during AIDS. PMID- 2904076 TI - Tumour necrosis factor and HIV: a note of caution. PMID- 2904077 TI - Two births after microsurgical sperm aspiration in congenital absence of vas deferens. PMID- 2904078 TI - Reversible limb-girdle muscular dystrophy. PMID- 2904079 TI - Surgery for epilepsy. PMID- 2904080 TI - Early predictors of prognosis in Guillain-Barre syndrome. PMID- 2904081 TI - Indigenised pharmaceuticals. PMID- 2904082 TI - The Bamako initiative. PMID- 2904083 TI - Floods and resistant malaria. PMID- 2904084 TI - Angiostrongylus cantonensis and eosinophilic meningitis. PMID- 2904085 TI - Papillomavirus screening of cervical lavages by polymerase chain reaction. PMID- 2904086 TI - All-terrain vehicles: hazard in Britain. PMID- 2904087 TI - Antitumour activity of histamine plus H2-receptor antagonist. PMID- 2904088 TI - Beneficial effects of maprotiline on irritative urinary symptoms in multiple sclerosis. PMID- 2904089 TI - Patients' rights and clinical research. PMID- 2904090 TI - Mental disorder in primary care. PMID- 2904091 TI - Prison, mental illness, and identity. PMID- 2904092 TI - Editorial freedom. PMID- 2904093 TI - Dexamethasone-induced bradycardia. PMID- 2904094 TI - Igor and Inna Uspensky. PMID- 2904095 TI - Thromboembolic events and germ cell malignancy. PMID- 2904096 TI - Carboplatin versus cisplatin. PMID- 2904097 TI - Increased kynurenic acid levels in Huntington's disease. PMID- 2904098 TI - Brain damage and hyponatraemia. PMID- 2904099 TI - Measles, mumps, and rubella vaccine: what coverage to block transmission? PMID- 2904100 TI - Hyperammonaemia and parenteral nutrition in infancy. PMID- 2904101 TI - Teaching vaginal examination. PMID- 2904103 TI - AIDS in the UK. PMID- 2904102 TI - Sterilisation and mental handicap. PMID- 2904104 TI - Training initiatives on drugs and HIV. PMID- 2904105 TI - Further studies on opioids and hibernation: delta opioid receptor ligand selectively induced hibernation in summer-active ground squirrels. AB - To examine the possible involvement of multiple opioid receptors in animal hibernation, we infused opioids selective for mu, kappa, and delta opioid receptors into summer-active ground squirrels (Citellus tridecemlineatus). The effects of those opioid treatments on the hibernation induced by HIT (Hibernation Induction Trigger) were also examined. Mu opioids morphine (1.50 mg/kg/day) and morphiceptin (0.82 mg/kg/day) and kappa opioid peptide dynorphin A (0.82 mg/kg/day) did not induce hibernation. On the contrary, morphine, morphiceptin and dynorphin A antagonized HIT-induced hibernation in summer-active ground squirrels. Infusion of delta opioid DADLE (D-Ala2-D-Leu5 enkephalin; 1.50 mg/kg/day), however, induced summer hibernation in a manner comparable to that induced by HIT. It is concluded therefore that delta opioid receptor and its ligand may be intimately involved in animal hibernation. In view of the fact that HIT was obtained from winter hibernating animals and might therefore be responsible for natural hibernation, our results also suggest that naturally occurring mu and kappa opioids may play an important role in the arousal state of hibernation. PMID- 2904106 TI - The effect of bombesin on basal, alpha-methyl-p-tyrosine, haloperidol, morphine, bremazocine and stress-induced prolactin secretion. AB - Intravenously administered bombesin lowered basal PRL levels in conscious male rats and prevented the morphine, bremazocine and stress-induced PRL secretion. The same dose of bombesin had no effect on PRL levels in alpha-methyl-p-tyrosine pretreated rats and did not affect haloperidol-stimulated PRL release. These results show that bombesin given intravenously acts as an inhibitor of PRL secretion and suggests that it does not act on the lactotrope itself but rather by an increase of the inhibitory dopaminergic tone. PMID- 2904107 TI - [Biological aspects of suicidal behavior]. PMID- 2904108 TI - The effect of antihypertensive medications on exercise performance: a review. AB - This review describes the effects of antihypertensive drugs on the performance of aerobic exercise. All available antihypertensive drugs lower blood pressure both at rest and decrease the rate of increase during exercise. However, they differ in their effects on exercise performance. The ideal antihypertensive agent should not have significant depressant effects on the myocardium, should not promote arrhythmias, should preserve the distribution of blood flow to exercising muscle, and should not interfere with substrate utilization. Diuretics, one of the most commonly prescribed class of antihypertensives, have few deleterious effects on exercise performance but have adverse metabolic effects; beta blockers have many adverse effects on exercise performance. Agents which have the least potential for adverse effects on exercise performance and metabolic effects are the converting enzyme inhibitors, calcium channel blockers, and alpha blockers, and central alpha agonists. The literature concerning each of these drugs is reviewed and recommendations are made for prescribing for the hypertensive who wishes to engage in vigorous exercise. PMID- 2904109 TI - Analysis of the primary structure of P-fimbrillins of uropathogenic Escherichia coli. PMID- 2904110 TI - Development of inflammation and augmented chemotactic responsiveness of murine peritoneal macrophages following treatment with Entamoeba histolytica trophozoites. AB - The accumulation of inflammatory cells in the peritoneal cavity of C57BL/6 mice was examined following intraperitoneal injection of Entamoeba histolytica trophozoites. Two different strains of E. histolytica were used: a virulent strain (IP:0682:1) and a non-virulent strain (DKB). Injection of 10(6) trophozoites of either strain resulted in significant increases in the numbers of total peritoneal cells, macrophages and polymorphonuclear cells as compared to either saline-injected control mice or mice injected with 10-fold lower doses of trophozoites. The in vitro chemotactic response of macrophages from amoebae induced exudates was also examined. Macrophages from mice treated with strain IP:0682:1 or DKB strain trophozoites were more responsive to complement-derived chemotactic factors than macrophages from saline-injected mice. This increase was significant on day 2 and persisted at enhanced levels until day 20 when the experiment was terminated. In addition, it was found that trophozoites activated normal mouse serum resulting in the production of serum-derived chemotactic activity. PMID- 2904111 TI - Investigation of minor components of Escherichia coli type 1 fimbriae: protein chemical and immunological aspects. AB - Three minor components of type 1 fimbriae, FimF, FimG and FimH have been characterized. These proteins are integrated in the fimbrial structure; are responsible for the adhesive properties of the fimbriae but are not necessary for the production of fimbriae. Fimbriae were purified from different clones harbouring various combinations of the fimF, fimG and fimH genes in addition to the fimA gene. The FimF, FimG and FimH proteins were identified by two dimentional gel electrophoresis. They were found to have molecular weights of 18.0 kDa, 17.0 kDa and 30 kDa, respectively. The ratio of FimF, FimG and FimH components to the major subunit was less than 1:100. The fimH protein especially was present in very small quantities. Sera raised against fimbriae from two of the clones (HB101/pPKL5 and HB101/pPKL4) were found by immunoblotting to be specific respectively for the major structural protein only (FimA), and for all components. PMID- 2904112 TI - The rabbit alpha-like globin gene cluster is polymorphic both in the sizes of BamHI fragments and in the numbers of duplicated sets of genes. AB - The alpha-like globin gene cluster in rabbits contains embryonic zeta-globin genes, an adult alpha-globin gene, and theta-globin genes of undetermined function. The basic arrangement of genes, deduced from analysis of cloned DNA fragments, is 5'-zeta 0-zeta 1-alpha 1-theta 1-zeta 2-zeta 3-theta 2-3'. However, the pattern of restriction fragments containing zeta- and theta-globin genes varies among individual rabbits. Analysis of BamHI fragments of genomic DNA from 24 New Zealand white rabbits revealed eight different patterns of fragments containing zeta-globin genes. The large BamHI fragments containing genes zeta 0 and zeta 1 are polymorphic in length, whereas a 1.9-kb fragment containing the zeta 2 gene and the 3.5-kb fragment containing the zeta 3 gene do not vary in size. In contrast to this constancy in the size of the restriction fragments, the copy number of the zeta 2 and zeta 3 genes does vary among different rabbits. No length polymorphism was detected in the BamHI fragments containing the theta globin genes, but again the copy number varies for restriction fragments containing the theta 2 gene. The alpha 1- and theta 1-globin genes are located in a nonpolymorphic 7.2-kb BamHI fragment. The combined data from hybridization with both zeta and theta probes shows that the BamHI cleavage pattern does not vary within the region 5'-alpha 1-theta 1-zeta 2-zeta 3-theta 2-3', but the pattern genomic blot-hybridization patterns for the progeny of parental rabbits with different zeta-globin gene patterns shows that the polymorphic patterns are inherited in a Mendelian fashion. Two different haplotypes have been mapped based on the genomic blot-hybridization data. The variation in the alpha-like globin gene cluster in the rabbit population results both from differences in the copy number of the duplication block containing the zeta-zeta-theta gene set and from the presence or absence of polymorphic BamHI sites. PMID- 2904113 TI - Excessive urinary excretion of methionine in mutant mice lacking D-amino-acid oxidase activity. AB - Thin-layer chromatography and amino acid analysis showed that mutant (ddY/DAO-) mice lacking D-amino-acid oxidase activity excreted about 3.5 times more methionine in urine than did normal (ddY/DAO+) mice. High-performance liquid chromatography using a chiral column showed that approximately 82% of urinary methionine of the ddY/DAO- mice had the D-configuration. Analysis revealed that the mouse diet used contained 0.04% free methionine and that approximately 46% of methionine was the D-isomer. When the ddY/DAO- mice were given a diet containing a low level of supplementary DL-methionine or a diet without D-methionine, they excreted the normal levels of methionine. These results indicate that the ddY/DAO mice were unable to metabolize D-methionine and excrete it in urine. PMID- 2904114 TI - [Vectors of malaria in rice paddies]. PMID- 2904115 TI - Iodination of [Tyr11]somatostatin yields a super high affinity ligand for somatostatin receptors in GH4C1 pituitary cells. AB - GH4C1 cells are a clonal strain of rat pituitary tumor cells which contain high affinity receptors for the inhibitory neuropeptide somatostatin (SRIF). In contrast to other peptides that bind to specific receptors on these cells, receptor-bound [125I-Tyr1]SRIF does not undergo rapid endocytosis. Rather, partial degradation to 125I-tyrosine occurs concomitantly with the dissociation of [125I-Tyr1]SRIF from cell surface receptors. In this study we characterize the binding, biological activity and receptor-mediated degradation of [125I Tyr11]SRIF, a SRIF analog that is radiolabeled in the center of the molecule. The binding of trace concentrations of [125I-Tyr11]SRIF (less than 50 pM) required 6 hr to reach equilibrium at 37 degrees compared with the 60 min required for [125I Tyr1]SRIF. Analysis of the kinetics of [125I- Tyr11]SRIF binding showed that the rate constant for association (kon = 1.7 x 10(8) M-8min-1) was similar to that for [125I-Tyr1]SRIF (0.8 x 10(8) M-1min-1). However, the two radioligands exhibited markedly different dissociation kinetics; the koff for [125I-Tyr11]SRIF was 0.002 min-1 compared with the value of 0.02 min-1 for [125I-Tyr1] SRIF. In agreement with its much slower rate of dissociation, [125I-Tyr11]SRIF bound to the SRIF receptor with higher affinity (Kd = 70 pM) than did [125I-Tyr1]SRIF (Kd = 350 pM). However, the apparent ED50 for [I-Tyr11]SRIF to inhibit cAMP accumulation (1.9 +/- 0.4 nM) was greater than the ED50 for SRIF (0.19 +/- 0.04 nM). The low potency of [I-Tyr11]SRIF probably resulted from the fact that subsaturating concentrations of this peptide did not achieve equilibrium binding during the 30-min incubation used to assay biological activity. As previously reported for [125I-Tyr1]SRIF, receptor-bound [125I-Tyr11]SRIF was not internalized and was released from the cells as a mixture of intact [125I Tyr11]SRIF (30%) and the degradation product 125I-tyrosine (65%). Only approximately 5% of receptor-bound [125I-Tyr11]SRIF was released as a different degradation product. Our data demonstrate that [125I-Tyr11]SRIF is a better radioanalog than [125I-Tyr1]SRIF for binding studies with intact cells because of its higher affinity for the SRIF receptor. In addition, inasmuch as receptor mediated degradation of bound ligand releases iodotyrosine from both position 1 and position 11 substituted analogs, aminopeptidases are unlikely to be entirely responsible for SRIF degradation. The superior binding properties of [125I Tyr11]SRIF should facilitate the detection of SRIF receptors in other cell types. PMID- 2904116 TI - Opioid responsiveness in patients with neuroleptic-induced akathisia. AB - Five patients with either acute or tardive neuroleptic-induced akathisia (5 weeks to 1 1/2 years duration) were videotaped before, during, and after a 2-week trial of propoxyphene (Darvon), 100 mg q.i.d., or acetaminophen (Tylenol) with 30 mg codeine, two tabs, q.i.d. Three "blinded" observers, experienced in movement disorders, rated the involuntary movements shown on the videotapes and agreed that, on opioids, all patients showed substantial to complete improvement of their stereotyped restless akathitic movements. Matching placebo was not beneficial. One patient who had improved on opioids was challenged with naloxone while on the opioids. There was a brief but severe reactivation of the akathisia. Our results suggest that opioids offer a selective therapy for patients with neuroleptic-induced akathisia and further suggest that the endogenous opiate system may be involved in patients with neuroleptic-induced akathisia. PMID- 2904117 TI - The relative selectivity of anticholinergic drugs for the M1 and M2 muscarinic receptor subtypes. AB - Anticholinergic drugs are used to treat a number of neurologic disorders, including parkinsonism, vestibular disturbances, and dystonia. Traditionally, these drugs have been thought to act in similar fashion, as competitive antagonists at a single class of muscarinic receptors, and not to differ significantly in their therapeutic efficacy. Recently, however, pharmacologic studies have shown that the novel antagonist pirenzepine is capable of recognizing heterogeneity among muscarinic receptors; high-affinity pirenzepine sites have been classified as M1 sites and low-affinity sites as M2. This study examined whether the anticholinergics currently available for treatment of neurologic symptoms have selectivity for these subtypes and whether they differ in their degree of selectivity; the study showed that these drugs do demonstrate selectivity. All had greater affinity for the M1 site, indicated by higher affinity for rat forebrain membranes, where M1 predominates, than hindbrain preparations, where M2 predominates. The degree of selectivity varied greatly; some compounds, such as ethopropazine, had little M1 selectivity, whereas others, such as scopolamine, trihexyphenidyl, and biperiden, were quite selective, like pirenzepine. It is unknown whether these differences in selectivity have any immediate therapeutic implications. However, these results support the emerging concept of muscarinic receptor subtypes and the prospect of developing more selective agents, with enhanced therapeutic efficacy. PMID- 2904118 TI - Natural history and treatment of tardive dystonia. AB - We retrospectively reviewed the clinical course and response to treatment of 67 patients with tardive dystonia. The age at onset ranged from 13 to 72 years without predilection to any particular age group or sex. Patients developed tardive dystonia even after relatively short duration of exposure to dopamine antagonists (21% within one year). Five of 42 patients withdrawn from these drugs remitted. Overall clinical improvement occurred in 52% of patients. Tetrabenazine and reserpine were most effective (greater than 50% response rate) in controlling dystonia. Anticholinergic drugs diminished dystonia in 46% of patients. PMID- 2904119 TI - Antiparkinsonian activity of (+)-PHNO in the MPTP-treated common marmoset. AB - Administration of MPTP (1-4 mg/kg ip daily for 5-7 days) to common marmosets induced persistent parkinsonian motor deficits. The subcutaneous administration of (+)-PHNO [(+)-4-propyl-9-hydroxynaphthoxazine; 1-4 micrograms/kg] caused a dose-dependent reversal of the akinesia and incoordination of movement. Similarly, oral administration of (+)-PHNO (5-20 micrograms/kg) caused an equivalent reversal of the motor abnormalities. No dyskinetic phenomena were induced by (+)-PHNO on oral or subcutaneous administration. Oral or subcutaneous administration of (+)-PHNO to normal control marmosets also increased the usual repetoire of motor behaviour, but this was not as marked as in MPTP-treated animals. (+)-PHNO is a potent dopamine agonist drug of potential use in the treatment of Parkinson's disease. PMID- 2904120 TI - Antiparkinsonian activity of a single oral dose of PHNO. AB - PHNO, a new D-2 agonist, was investigated in five patients with Parkinson's disease. In an acute, open, oral, dose-ranging study comparing benefit from single doses, 4 mg of PHNO was found to be equivalent to one tablet of Sinemet 25/250 mg. Adverse reactions were those anticipated for a dopaminomimetic agent. Because of its novel structure and apparent transcutaneous penetration, further studies on PHNO are desirable. PMID- 2904121 TI - The autonomic nervous system in Gilles de la Tourette's syndrome. AB - Twenty-three patients with Gilles de la Tourette's syndrome (GTS) underwent noninvasive investigation of autonomic nervous system (ANS) function, as did 23 age-matched controls. ANS function in GTS patients was no different from that of controls, and patients receiving neuroleptic drugs had the same ANS function as untreated patients. All 23 patients later received clonidine and were retested. The ANS values before administration of clonidine were compared with those while patients were taking clonidine. The only significant change (p less than 0.01) with clonidine was a reduced resting pulse rate. The combination of clonidine and neuroleptic drugs did not induce significant autonomic changes compared with neuroleptic therapy alone. These results indicate that the ANS in GTS patients is normal and that the drugs used to abate tics do not produce clinically significant changes in ANS when chronically given. The findings suggest that the pathophysiology and treatment of GTS do not directly involve the nuclei or tracts of autonomic regulation. PMID- 2904122 TI - Tardive dystonia in patients with Tourette's syndrome. AB - We describe two patients with Gilles de la Tourette's syndrome (TS) who developed tardive dystonia after treatment with neuroleptics. The dystonic movements persisted after the offending drugs were stopped and improved with tetrabenazine. Tardive dystonia in TS has not been documented previously. PMID- 2904123 TI - A copia-like transposable element family in Arabidopsis thaliana. AB - The fast generation time, small genome size and extensive genetic map of the crucifer Arabidopsis thaliana have made it the subject of an increasing number of studies in plant molecular genetics. As transposable elements have greatly facilitated genetic analysis in a variety of species, we have attempted to identify an endogenous A. thaliana transposable element. We report here the discovery of a family of such elements, which we refer to as Ta1 elements. Sequence analysis of one such element shows that it is closely related to retrotransposons and integrated retroviral proviruses, being bound by a direct sequence repeat and having an open reading frame with clear sequence similarity to the polyprotein of the Drosophila melanogaster retrotransposon copia. The sequence of an empty target site of a Ta1 element shows that insertion is accompanied by a five-base-pair target-site duplication and that Ta1 has transposed in the period of time since divergence of two races of A. thaliana. PMID- 2904124 TI - Transient association of newly synthesized unfolded proteins with the heat-shock GroEL protein. AB - It has been suggested that newly synthesized proteins are maintained in their unfolded state by cellular ATP-driven factors which may prevent or reverse the formation of misfolded structures or promote the correct assembly of oligomeric proteins or post-translational secretion. Using a photocross-linking approach, we have identified the 20S heat-shock GroEL protein as the major cytosolic component which forms a complex with the unfolded newly synthesized pre-beta-lactamase or chloramphenicol acetyltransferase in Escherichia coli. Dissociation of these complexes is ATP-dependent. The unfolded state of pre-beta-lactamase, maintained by the transient interaction with GroEL, may be essential for the secretion of this protein. PMID- 2904125 TI - Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger in the brain. AB - In the vascular system, endothelium-derived relaxing factor (EDRF) is the name of the local hormone released from endothelial cells in response to vasodilators such as acetylcholine, bradykinin and histamine. It diffuses into underlying smooth muscle where it causes relaxation by activating guanylate cyclase, so producing a rise in cyclic GMP levels. It has been known for many years that in the central nervous system (CNS) the excitatory neurotransmitter glutamate can elicit large increases in cGMP levels, particularly in the cerebellum where the turnover rate of cGMP is low. Recent evidence indicates that cell-cell interactions are involved in this response. We report here that by acting on NMDA (N-methyl-D-aspartate) receptors on cerebellar cells, glutamate induces the release of a diffusible messenger with strikingly similar properties to EDRF. This messenger is released in a Ca2+-dependent manner and its activity accounts for the cGMP responses that take place following NMDA receptor activation. In the CNS, EDRF may link activation of postsynaptic NMDA receptors to functional modifications in neighbouring presynaptic terminals and glial cells. PMID- 2904126 TI - Fibrils from brains of cows with new cattle disease contain scrapie-associated protein. AB - During the past two years, more than 1,000 cases of a neurological disorder of cattle, bovine spongiform encephalopathy (BSE), have been confirmed from farms throughout Great Britain. The neurological signs and brain pathology of BSE resemble those produced in other species by the pathogens of scrapie and related disorders. The discovery of fibrils similar to scrapie-associated fibrils in detergent extracts o BSE-affected brain supported the clinical and pathological diagnosis of the disease, but has been controversial. Scrapie-associated fibrils are found in brain extracts of all species affected by scrapie and diseases caused by related pathogens. They are pathological aggregates of a neuronal membrane protein termed PrP and a protease-resistant form of PrP is a molecular marker of scrapie-associated fibrils. In this report, we show the major protein of BSE fibrils is the bovine homologue of PrP as judged by its size, protease resistance, immunoreactivity, lectin binding and partial N-terminal protein sequence. This confirms that BSE is a scrapie-like disease. PMID- 2904127 TI - DNA transformation leads to pilin antigenic variation in Neisseria gonorrhoeae. AB - Many pathogenic bacteria express pili (fimbriae) on their cell surfaces. These structures mediate binding of bacteria to host tissues, and may also be involved in other aspects of pathogenesis. Neisseria gonorrhoeae pili are mainly composed of a single protein, pilin, whose expression is controlled at chromosomal expression loci (pilE). An intact pilin gene and promoter sequences are only found at pilE. Strain MS11 contains two expression sites (pilE1 and pilE2), whereas several of its derivatives and other clinical isolates contain only one. Silent pilin loci (pilS1-pilS7) contain truncated variant pilin genes lacking the promoter and conserved pilin gene sequences. Pilin antigenic variation in N. gonorrhoeae occurs by DNA recombination between one of he silent partial variant gene segments in pilS and an expressed pilin gene in pilE. The recombination reactions are nonreciprocal, and therefore the mechanism has been classified as gene conversion. We report that much of the recombination between pilin loci actually occurs after transformation of living piliated cells by DNA liberated from lysed cells within a population. This constitutes a new molecular mechanism for an antigenic variation system, as well as the first specific function for a DNA transformation system. PMID- 2904128 TI - Abdominal segmentation of the Drosophila embryo requires a hormone receptor-like protein encoded by the gap gene knirps. AB - The body pattern along the anterior-posterior axis of the insect embryo is thought to be established by two organizing centres localized at the ends of the egg. Genetic analysis of the polarity-organizing centres in Drosophila has identified three distinct classes of maternal effect genes that organize the anterior, posterior and terminal pattern elements of the embryo. The factors provided by these gene classes specify the patterns of expression of the segmentation genes at defined positions along the longitudinal axis of the embryo. The system responsible for organizing the posterior segment pattern is a group of at least seven maternal genes and the zygotic gap gene knirps (kni). Their mutant phenotype has adjacent segments in the abdominal region of the embryo deleted. Genetic analysis and cytoplasmic transplantation experiments suggested that these maternal genes are required to generate a 'posterior activity' that is thought to activate the expression of kni (reviewed in ref. 2). The molecular nature of the members of the posterior group is still unknown. Here we report the molecular characterization of the kni gene that codes for a member of the steroid/thyroid receptor superfamily of proteins which in vertebrates act as ligand-dependent DNA-binding transcription regulators. PMID- 2904129 TI - Pronounced facilitation of endogenous noradrenaline release by presynaptic beta 2 adrenoceptors in the vasculature of freely moving rats. AB - The facilitation of the noradrenaline (NA) overflow by stimulation of the presynaptic beta-adrenoceptor of the rat portal vein was investigated, using the freely moving unanesthetized permanently cannulated rat as a model. The beta 2 selective agonist fenoterol caused a maximal enhancement of about 300% of the basal NA level at a dose of 0.5 mg/kg. Following administration of cocaine (2.5 mg/kg plus 0.05 mg/kg/min) basal NA levels increased to 150% whereas combination of cocaine and fenoterol results in a dose dependant rise up to over 560% of the basal level (at a fenoterol dosage of 0.5 mg/kg). Blockade of the alpha 2 adrenoceptors with yohimbine (0.5 mg/kg) which enhances the NA level to 486%, followed by 0.125 mg/kg fenoterol results in a further 2.53-fold rise to more than 1,200% of the basal level, indicating the pronounced counterregulatory role of the presynaptic alpha 2-adrenoceptor. After ganglionic blockade with hexamethonium (3 mg/kg plus 6 mg/kg/h) the effect of yohimbine (0.5 mg/kg) alone was diminished to 162%, but the additional facilitatory effect of 0.125 mg/kg fenoterol still was 1.82-fold, to 294% of the basal level. Combination of cocaine (2.5 mg/kg plus 0.05 mg/kg/min), yohimbine (0.5 mg/kg) and fenoterol (0.125 mg/kg) induced a rise to over 9,000 pg/ml NA (about 40-fold of the basal NA level). During electrical stimulation (2 Hz, 3 ms, 5 mA) of the local portal vein nervous plexus, the role of the inhibitory alpha 2-adrenoceptor becomes even more pronounced.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2904130 TI - Loss of selectivity of so-called selective alpha 1-adrenoceptor agonists after phenoxybenzamine. AB - This study examined the nature of alpha-adrenoceptor subtype involved in pressor responses to so-called selective alpha 1-adrenoceptor agonists after treatment with phenoxybenzamine in vivo. The influence of prazosin (0.1 mg/kg) and of yohimbine (1 mg/kg) on the dose-response curves for cirazoline in the pithed rat, and for phenylephrine in the anaesthetized dog were compared, after various doses of phenoxybenzamine. In the pithed rat, after 0.05 mg/kg phenoxybenzamine, prazosin caused a displacement of the dose-response curve of cirazoline to the right which was much larger than that caused by yohimbine; after 0.3 mg/kg phenoxybenzamine, prazosin and yohimbine caused about equal displacements; after 1 mg/kg phenoxybenzamine, yohimbine caused a marked displacement, while prazosin was without effect. In the anaesthetized dog, after 1 mg/kg phenoxybenzamine, prazosin and yohimbine produced about equal rightward shifts of the dose-response curve for phenylephrine. However, after 3 mg/kg phenoxybenzamine the rightward shift of the dose-response curve for phenylephrine was much larger after yohimbine than after prazosin. In the anaesthetized dog, verapamil (1 mg/kg) caused a small and parallel rightward shift of the dose-response curve for phenylephrine before phenoxybenzmine and a large and nonparallel one after phenoxybenzamine (3 mg/kg); the effect of verapamil on responses to the selective alpha 2-adrenoceptor agonist UK-14,304 (before and after phenoxybenzamine) were similar to those on responses to phenylephrine after phenoxybenzamine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2904131 TI - Neurobehavioral effects of intrathecal somatostatinergic treatment in subhuman primates. AB - We infused somatostatin and its long-acting analogue (SMS 201-995) into the intracranial subarachnoid space of eight monkeys. Chronic infusions of SMS 201 995 produced marked neurotoxic effects characterized by truncal ataxia, dysmetria, and severe bradykinesia, with normal level of consciousness. Subcutaneous injection of apomorphine, a dopaminergic agonist, promptly reversed these effects. Further studies are required before intrathecal somatostatin replacement therapy can be offered to patients with Alzheimer's disease. PMID- 2904132 TI - [The role of the amyl nitrite inhalation test in the detection of ischemic heart diseases]. PMID- 2904133 TI - Pig Hox-2.4 has accumulated a frameshift mutation relative to mouse Hox-2.4. PMID- 2904134 TI - Nucleotide sequence of chloroplast CF1-ATPase epsilon-subunit and elongator tRNAMet genes from Arabidopsis thaliana. PMID- 2904135 TI - Isolation and mapping of a polymorphic DNA sequence (pHHH208) on chromosome 14 [D14S19]. PMID- 2904136 TI - Isolation and mapping of a polymorphic DNA sequence (pMHZ17) on chromosome 13 [D13S51]. PMID- 2904137 TI - Isolation and mapping of a polymorphic DNA sequence (pYNH20) on chromosome 13 [D13S50]. PMID- 2904138 TI - Isolation and mapping of a polymorphic DNA sequence (pEFD70.2) on chromosome 10 [D10S26]. PMID- 2904139 TI - Isolation and mapping of a polymorphic DNA sequence (pKKA40) on chromosome 9q [D9S31]. PMID- 2904140 TI - Isolation and mapping of a polymorphic DNA sequence (pMHZ21) on chromosome 9q [D9S30]. PMID- 2904141 TI - Subdural empyemas in children. AB - Subdural empyema is a neurosurgical emergency which is rapidly fatal if not recognized and managed promptly. Most series report a 30-40% mortality, and recommend a craniotomy along with aggressive medical therapy. Between 1978 and 1986, 8 children (2 months to 13 years) with subdural empyemas were diagnosed and treated at our institution, and form the basis for this study. Burr hole and catheter drainage was the treatment of choice in 5 children, while craniotomy was required in 1 case of sinusitis with osteomyelitis. Three infants received multiple subdural taps via the anterior fontanel. All patients responded to surgical intervention and antibiotic therapy. The average follow-up period was 29 months, and 5 children had no developmental delay, decrease in school performance, or impairment of intellectual function. There were no deaths in our series. Although the surgical management of subdural empyemas remains controversial, it appears that burr hole and catheter drainage is sufficient in most cases. With earlier diagnosis, aggressive antibiotic therapy, and timely surgical intervention, the morbidity and mortality of subdural empyemas have significantly diminished in recent years. PMID- 2904142 TI - Kidney stones. How new technology has improved management. AB - In the past decade, techniques allowing noninvasive or relatively noninvasive treatment of kidney stones have replaced standard surgical management for most patients. Extracorporeal shock wave lithotripsy is suitable for the majority of patients with calculi in the upper or mid urinary tract. Ultrasonic lithotripsy can be used to fragment large staghorn or cystine calculi and is suitable for morbidly obese patients. The tunable pulsed dye laser is also gaining a role in the treatment of selected patients. All three techniques require only a short hospital stay. PMID- 2904143 TI - Antagonistic properties of RU 24969, a preferential 5-HT1 receptor agonist, at presynaptic alpha 2-adrenoceptors of central and peripheral neurones. AB - The effect of RU 24969 (5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)-1 H-indole) on the electrically evoked 3H overflow was studied in superfused rat brain cortex slices preincubated with 3H-noradrenaline or 3H-serotonin and in superfused segments of the rat vena cava preincubated with 3H-noradrenaline. In cortex slices preincubated with 3H-noradrenaline, RU 24969 facilitated the electrically (3 Hz) evoked 3H overflow. This effect was abolished by phentolamine but was not affected by desipramine or the 5-HT3 receptor antagonist ICS 205-930. The concentration-response curve of noradrenaline for its inhibitory effect on the evoked overflow (determined in the presence of desipramine) was shifted to the right by RU 24969 32 and 100 mumol/l. In this respect, RU 24969 was about 500 times less potent than phentolamine. In cortex slices preincubated with 3H serotonin, the inhibitory effect of 3.2 mumol/l RU 24969 on the electrically evoked 3H overflow was increased by phentolamine. In segments of the vena cava, RU 24969 inhibited the electrically (0.66 Hz) evoked 3H overflow. The concentration-response curve of RU 24969 was U-shaped, since at concentrations higher than 0.1 mumol/l the extent of inhibition decreased with increasing concentrations of RU 24969. In the presence of phentolamine, the concentration dependent attenuation of the RU 24969-induced inhibition of overflow was no longer detectable. The present results suggest that RU 24969 is a weak antagonist at presynaptic alpha 2-adrenoceptors (by more than 2.5 log units less potent than as an agonist at presynaptic 5-HT1B auto- and heteroreceptors). PMID- 2904144 TI - [Psychotropic properties of ovarian estrogens]. PMID- 2904145 TI - Effect of dl-demethylcoclaurine on alpha and beta-adrenergic receptors. PMID- 2904146 TI - Cloning and nucleotide sequence of human gamma-glutamyl transpeptidase. AB - We have identified the gene for human gamma-glutamyl transpeptidase [GGT; glutamine:D-glutamyl-peptide 5-glutamyltransferase (also called gamma glutamyltransferase), EC 2.3.2.2] in a BCR gene-related region located in band q11----qter of chromosome 22. Two cDNAs complementary to the GGT mRNA have been isolated from a human placental library constructed in phage lambda gt11. The largest cDNA has a size of 2535 base pairs (bp) and an open reading frame of 1707 nucleotides encoding 569 amino acids. By using a probe corresponding to this cDNA, a mRNA of approximately 2.4 kilobases was detected by RNA blot hybridization analysis in mouse kidney RNA. The GGT precursor encoded by the coding sequence would have an estimated Mr of 61,400. We compared our nucleotide and deduced amino acid sequences with the published results of rat kidney cDNAs. The human and rat amino acid sequences are similar; however, a considerable discrepancy in nucleotide sequence was found within a 180-bp fragment of the heavy chain, resulting in a completely different amino acid sequence for this region. In addition, the 5' untranslated sequence of the human cDNA (669 bp) is substantially larger than that determined in the rat cDNA (227 bp). Our results may be valuable for further studies on the protein structure of human GGT as well as studies on the regulation of the enzyme. PMID- 2904147 TI - Probing the Escherichia coli glnALG upstream activation mechanism in vivo. AB - In vivo "footprints" of the glnA regulatory region under activating conditions demonstrate that the three most upstream activator sequences bind the protein NRI in the cell. Together, protections at these sites span six of seven consecutive major grooves and lie on the same helix face. E sigma 54 protects two major grooves of DNA approximately 60 base pairs downstream at the glnAp2 promoter and primarily on the opposite helix face. Experiments using potassium permanganate to probe open complex formation in vivo demonstrate that NRI is absolutely required for E sigma 54 to open the promoter DNA. Together, the dimethyl sulfate and permanganate studies verify [Reitzer, L. J., Bueno, R., Cheng, W. D., Abrams, S. A., Rothstein, D. M., Hunt, T. P., Tyler, B. & Magasanik, B. (1987) J. Bacteriol. 169, 4279-4284] that E sigma 54 occupies the glnAp2 promoter in a closed complex in vivo even in the presence of excess nitrogen and the absence of NRI. Furthermore, the slow step in transcriptional activation is shown to be an NRI dependent conformational change in the downstream promoter DNA, which results in DNA melting. These observations place interesting restrictions on models describing the mechanism by which NRI activates transcription from glnAp2 at a distance. PMID- 2904148 TI - Inhibition of H+-transporting ATPase by formation of a tight nucleoside diphosphate-fluoroaluminate complex at the catalytic site. AB - Inhibition of the mitochondrial and bacterial F1-type ATPases [of ATP phosphohydrolase (H+-transporting), EC 3.6.1.34] by fluoride was found to depend on the presence of aluminum and ADP at the catalytic site(s) of F1-type ATPase. AIF-4 was demonstrated to be the active fluoroaluminate species. The identical pattern of inhibition of F1-type ATPase activity obtained in the presence of ADP and NaF with beryllium, a metal that forms fluoride complexes strictly tetracoordinated, suggests that aluminum acts through a tetrahedral complex. Inhibition of isolated F1-type ATPase by AIF-4 in the presence of ADP cannot be reversed by ADP, ATP, or chelators of aluminum. However, the inhibition of the ATPase activity of the F1 sector in submitochondrial particles caused by AIF-4 and ADP was reversed upon addition of an oxidizable substrate. Uncouplers prevented the reversal of inhibition, suggesting that the protonmotive force generated by respiration was responsible for the relief of inhibition. Because of structural similarities between AIF4- and , AIF4- is postulated to mimic the phosphate group of ATP and form an abortive complex with ADP at the active site(s) of F1-type ATPase. PMID- 2904149 TI - Evidence that a point mutation in dihydrofolate reductase-thymidylate synthase confers resistance to pyrimethamine in falciparum malaria. AB - Analysis of a genetic cross of Plasmodium falciparum and of independent parasite isolates from Southeast Asia, Africa, and South America indicates that resistance to pyrimethamine, an antifolate used in the treatment of malaria, results from point mutations in the gene encoding dihydrofolate reductase-thymidylate synthase (EC 1.5.1.3 and EC 2.1.1.45, respectively). Parasites having a mutation from Thr 108/Ser-108 to Asn-108 in DHFR-TS are resistant to the drug. The Asn-108 mutation occurs in a region analogous to the C alpha-helix bordering the active site cavity of bacterial, avian, and mammalian enzymes. Additional point mutations (Asn-51 to Ile-51 and Cys-59 to Arg-59) are associated with increased pyrimethamine resistance and also occur at sites expected to border the active site cavity. Analogies with known inhibitor/enzyme structures from other organisms suggest that the point mutations occur where pyrimethamine contacts the enzyme and may act by inhibiting binding of the drug. PMID- 2904150 TI - Long-term potentiation differentially affects two components of synaptic responses in hippocampus. AB - We have used low magnesium concentrations and the specific antagonist D-2-amino-5 phosphonopentanoate (D-AP5) to estimate the effects of long-term potentiation (LTP) on the N-methyl-D-aspartate (NMDA) and non-NMDA receptor-mediated components of postsynaptic responses. LTP induction resulted in a considerably larger potentiation of non-NMDA as opposed to NMDA receptor-related currents. Increasing the size of postsynaptic potentials with greater stimulation currents or with paired-pulse facilitation produced opposite effects; i.e., those aspects of the response dependent on NMDA receptors increased to a greater degree than did those components mediated by non-NMDA receptors. These results pose new constraints on hypotheses about the locus and nature of LTP and strongly suggest that postsynaptic modifications are part of the effect. PMID- 2904152 TI - Effects of growth hormone-releasing factor and somatostatin on growth hormone secretion in hypophysial stalk-transected beef calves. AB - The effects of growth hormone-releasing factor (GHRF) on growth hormone (GH) secretion were studied in beef calves after hypophysial stalk transection (HST). Peripheral GH concentration during surgery was elevated for 60 min after the initiation of anesthesia to 15 ng/ml, which was greater than plasma levels after HST and during the recovery period (0-30 hr mean, 3 ng/ml; P less than 0.05). Episodic GH secretion normally seen in sham-operated controls (SOC) was abolished after HST. Before HST, calves responded to 80% of the GHRF challenges, whereas after HST calves responded to every challenge of GHRF with an increase in plasma GH. A dose of 0.067 microgram human pancreatic (hp) hpGHRF(1-40)OH/kg body wt 3 days after HST increased plasma GH to 55 ng/ml from a control period mean of 5 ng/ml (P less than 0.04). On Day 8, HST calves received two injections of 0.067 microgram hpGHRF/kg body wt at 3-hr intervals, with feeding 70 min after the first injection. During two preinjection control periods, basal GH averaged less than 4 ng/ml and increased to 17 (P less than 0.02) and 9 (P less than 0.04) ng/ml immediately after the first and second injection of hpGHRF, but the response declined over the 8-day period after surgery. On Days 19 and 20, the HST calves were infused iv with 0.033 and 0.067 microgram somatostatin(SS)-14 (SRIH)/kg body wt, during which a pulse injection of 0.067 microgram hpGHRF/kg body wt was administered. GH increased to 9 and 5 ng/ml during the 0.033- and 0.067-microgram SRIH infusions after GHRF; no somatotropic rebound was observed after the SRIH was discontinued as was seen in the animals while the hypothalamic hypophysial connections were intact. Five and six months after HST the responses to two analogs of rat hypothalamic GHRF were similar to those in SOC calves. These results indicate that HST calves responded to exogenous GHRF with an abrupt increase in plasma GH, but GH response to GHRF during SRIH infusion was greatly inhibited. PMID- 2904151 TI - Antiserum raised against residues 159-168 of the guanine nucleotide-binding protein Gi3-alpha reacts with ependymal cells and some neurons in the rat brain containing cholecystokinin- or cholecystokinin- and tyrosine 3-hydroxylase-like immunoreactivities. AB - Antibodies raised against a synthetic deca-peptide corresponding to a specific sequence of Gi3-alpha protein (an inhibitory guanine nucleotide-binding protein) were used to analyze Gi3-alpha-like immunoreactivity in brain sections from colchicine-treated rats by indirect immunofluorescence histochemistry. Gi3-alpha peptide-positive cell bodies were found in the ventral tegmental area and substantia nigra, and these cells were also cholecystokinin (CCK)- and tyrosine 3 hydroxylase-positive. Gi3-alpha-peptide staining was observed in perikarya in the hippocampus and in fibers in the nucleus accumbens, tuberculum olfactorium, bed nucleus of stria terminalis, and a spino-thalamic tract, where it coexisted with CCK-like immunoreactivity as well. No coexistence with CCK occurred in Gi3-alpha peptide-positive ependymal cells outlining the aqueduct and ventricles. Preadsorption of Gi3-alpha antibodies with CCK-8 or CCK-33 did not alter Gi3 alpha-peptide staining. The occurrence of Gi3-alpha-peptide-like immunoreactivity in CCK-containing neurons may indicate the presence of Gi3-alpha protein and in CCK/dopamine neurons may indicate an association of this Gi protein with dopamine autoreceptors. PMID- 2904153 TI - Dual effect of dihydroergotamine at vascular 5-hydroxytryptamine receptors in pithed rats. AB - Dihydroergotamine (DHE), administered intravenously to pithed normotensive rats, increased the mean arterial blood pressure dose-dependently. This pressor effect was noncompetitively inhibited by the 5-hydroxytryptamine (5-HT) receptor antagonists pizotifen and cyproheptadine (0.1 mg/kg each). The alpha 1 adrenoceptor blocker prazosin (1 mg/kg) had no influence on the DHE effect whereas the alpha 2-adrenoceptor blocker yohimbine, at the same dose, proved to be a noncompetitive inhibitor of this pressor effect. The results indicate that both the 5-HT receptors and alpha 2-adrenoceptors are involved in the DHE-induced vasoconstriction. On the other hand, in pithed normotensive rats, DHE proved to be a potent inhibitor of the pressor response to 5-HT but it did not inhibit that to noradrenaline. The results obtained characterize DHE as a noncompetitive dualist at vascular 5-HT receptors. PMID- 2904154 TI - Novel autonomic neurotransmitters and upper gastrointestinal function. AB - The evidence for, and possible roles of, inhibitory and excitatory non adrenergic, non-cholinergic (NANC) nerves supplying smooth muscle, and the effects of putative transmitter candidates are considered for each of three main regions of the upper gastrointestinal tract: (A) the smooth muscle portion of the oesophagus and the oesophagogastric junction, (B) the stomach (fundus, body and antrum) and gastroduodenal junction and (C) the biliary tract and choledochoduodenal junction. The major points from human tissues are as follows: 1. Inhibitory (NANCI) nerves appear to be present in the muscularis externa of oesophagus, stomach and duodenum, with greater density in the circular than in the longitudinal muscle. 2. NANCI nerves are present in high density at the oesophagogastric and choledochoduodenal junctions. They may also be present at the gastroduodenal junction. The gall-bladder may have a very sparse NANCI innervation. 3. Excitatory (NANCE) nerves appear to be present throughout the upper gastrointestinal tract. 4. Many candidates need at present to be considered for the role of NANCE transmitter(s) in the human upper gastrointestinal tract but substance P still seems a likely contender for this role. 5. Fewer candidates are at present generally available for the role of NANCI transmitter(s), with VIP and ATP being leading contenders. However, in the human upper gastrointestinal tract the evidence for ATP is not good, and VIP still remains the favourite candidate except in the gall-bladder, where its role remains to be elucidated. PMID- 2904155 TI - Alpha 2-adrenoceptor blockade attenuates feeding behavior induced by neuropeptide Y and epinephrine. AB - Neuropeptide Y (NPY, 0.47 nmol) and epinephrine (28.9 nmol) evoked robust, and quantitatively similar, increments in food intake and local eating rate following administration into the third cerebral ventricle (IIIV). Whereas IIIV pretreatment with phentolamine (71 nmol), a nonselective alpha-adrenoceptor antagonist, or prazosin (9.5 nmol), a selective alpha 1-adrenoceptor antagonist, was without effect on NPY-induced feeding behavior, pretreatment with the alpha 2 adrenoceptor antagonist yohimbine (15 nmol) dramatically attenuated the stimulatory effects of NPY or epinephrine on both food intake (by over 50%) and local eating rate. Additionally, yohimbine administered alone was associated with a stimulatory effect on food intake for the periods of 80-110, and 110-140 minutes posttreatment. These data demonstrate that feeding behavior induced by IIIV administration of NPY or epinephrine is attenuated by prior blockade of alpha 2-adrenoceptors and suggest that, as in other systems innervated by neurons displaying NPY and adrenergic transmitter colocalization, the effects of NPY on feeding behavior may, at least in part, be mediated via alpha 2-adrenoceptors. PMID- 2904156 TI - [Early effects of the influence of ionizing radiation in relatively small doses on the neuromediator systems responding to the central regulation of the hypothalamo-pituitary-adrenal cortex system]. AB - In experiments with mature Wistar male rats changes of mediator interrelations in different brain parts, responsible for the central regulation of the hypothalamo pituitary-adrenocortical system, were detected at early times after whole-body X irradiation with a dose of 12.9 mC/kg. These changes represent one of the major mechanisms leading, at later times after irradiation, to the development of syndromes related to diencephalic disturbances. PMID- 2904157 TI - Differential metabolic pattern of muscle and liver after the administration of a beta-adrenergic agonist. PMID- 2904158 TI - Effect of Eimeria tenella infection on the caecal population of lincomycin resistant Clostridium perfringens introduced into chickens. AB - The effect of Eimeria tenella infection on the caecal population of lincomycin resistant Clostridium perfringens (KGW 851) newly introduced into chickens was studied. Four groups of chickens consisted of: (1) Uninoculated controls; (2) inoculated with C perfringens (KGW 851); (3) inoculated with E tenella; and (4) inoculated with C perfringens (KGW 851) followed by E tenella. Five chickens in each group were necropsied on each of days 0, 3, 5, 7, 10 and 14 after the E tenella inoculation. The mean total C perfringens counts in the caecal contents increased at five days after E tenella inoculation and reached maximum counts at seven days after the inoculation. Also lincomycin-resistant C perfringens readily established itself at approximately one 10th of the total C perfringens population in the presence or absence of E tenella infection. PMID- 2904159 TI - [Current findings in the pathogenesis and treatment of urinary infections]. PMID- 2904160 TI - [The current posture on radioisotope exploration in chronic diffuse hepatopathies]. PMID- 2904161 TI - [Lipids and joint inflammation]. PMID- 2904162 TI - [Serum level of tumor markers (antigen Ca 19-9, CEA, ferritin) in digestive tumors. Their diagnostic usefulness]. PMID- 2904163 TI - [Colorectal cancer, a complication of ulcerohemorrhagic rectocolitis]. PMID- 2904164 TI - [Lectin receptors--markers of colorectal adenomatous dysplasia]. PMID- 2904165 TI - [The prevention of accidents during proximal digestive endoscopy]. PMID- 2904166 TI - [The place for a method of demonstrating native anti-DNA antibodies in the diagnosis of systemic lupus erythematosus using an indirect immunofluorescence technic]. PMID- 2904167 TI - [Hairy cell leukemia: its clinical evolution, prognostic factors and therapeutic results. A prospective study]. PMID- 2904168 TI - [Cryoglobulin study in glomerular nephropathies]. PMID- 2904169 TI - [Evian, the force of balance]. PMID- 2904170 TI - [Premedications]. PMID- 2904171 TI - Low degree of DNA polymorphism in the HLA-linked lymphotoxin (tumour necrosis factor beta) gene. AB - Tumour necrosis factors (TNF) alpha (cachectin) and beta (lymphotoxin) are lymphokines with many biological activities. For example, the molecules regulate the immune system, which is of special interest since the genes for the TNF are located within the human major histocompatibility complex (MHC). The MHC encodes HLA-molecules that play a critical role in the cellular interactions of the immune response. To test whether genetic polymorphism in the TNF genes may be involved in the associations between HLA and autoimmune diseases, we here describe an analysis of DNA polymorphism in the human TNF-beta gene. The results show that the TNF-beta gene has only a low degree of DNA polymorphism, and that this is not associated with HLA antigens showing a strong association with autoimmune-like diseases. PMID- 2904172 TI - Induction of interleukin-2 production in CD4+ and CD8+ T-cell subsets after activation via CD3 and CD2. AB - The activation signals necessary for interleukin-2 (IL-2) receptor induction, IL 2 production, and DNA synthesis in resting T cells were investigated. IL-2 receptors were induced after activation via CD2 or CD3 alone, while IL-2 production in both CD4+ and CD8+ T cells required activation via both CD3 and CD2. The sequence of activation signals via CD3 and CD2 was shown to be important since DNA synthesis was induced when the primary activation signal was delivered via CD3, and the CD2 signal within 8 h. In contrast, no DNA synthesis was demonstrated when the primary activation signal was delivered via CD2 and the CD3 signal later. Ciclosporin A (CyA) inhibited T-cell DNA synthesis after activation via CD2 and CD3. The inhibition seemed to be due to the prevention of IL-2 synthesis. PMID- 2904173 TI - Homeobox linked to gene control. PMID- 2904174 TI - Carving up the human genome. PMID- 2904175 TI - [Antacids and gastroduodenal topical drugs]. PMID- 2904176 TI - [Private practice. A developing practice]. PMID- 2904177 TI - Fingerprinting cell lines: use of human hypervariable DNA probes to characterize mammalian cell cultures. AB - Hypervariable DNA sequences may be used as probes to derive DNA "finger-prints" for individuals. To assess the use of the human 33.15 and 33.6 probes (isolated by Jeffreys and coworkers) for characterizing cell lines of nonhuman origin, DNA from different stocks of Chinese hamster (CH) cells was screened. All CHO (ovary) sublines could be readily distinguished from CH-V79 sublines by their fingerprints, but where two stocks had been derived recently from the same line, their fingerprints were nearly identical. Similarly fingerprints of HPRT deficient mutants derived from one cell stock were identical. A V79 x CHO fusion hybrid showed equal fingerprint band-sharing with each parent line, while early passage diploid CH cells had a fingerprint closer to CHO than to V79. Thus these data introduce a simple means of typing cell lines to avoid cross-contamination, of checking cell hybrids, and of assessing the divergence of cell stocks from one another. PMID- 2904178 TI - Further characterization of a somatic cell mutant defective in regulation of 3 hydroxy-3-methylglutaryl coenzyme A reductase. AB - Two enzymes of mammalian cellular mevalonate biosynthesis, 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) synthase and HMG-CoA reductase, have been shown to be regulated by exogenous sterols. It has been demonstrated that these enzymes are regulated, at least in part, by transcriptional control of their synthesis. We have previously described a somatic cell mutant (CR1) of the CHO-K1 cell line that is defective in regulation of the activity of these enzymes in response to exogenous sterols. In this report, we demonstrate that this mutant is defective in regulation of the mRNA levels for HMG-CoA reductase and HMG-CoA synthase by 25-hydroxycholesterol and mevinolin. In the case of HMG-CoA reductase, this loss of apparent transcriptional control is not accompanied by a comparable loss in regulation of synthesis of this enzyme. This observation is consistent with prior studies suggesting that HMG-CoA reductase can be regulated translationally. We also show that CR1 cells exhibit a constitutively rapid rate of degradation of HMG-CoA reductase. PMID- 2904179 TI - Influence of a habitual high egg intake on serum lipid levels in a rural coloured population. AB - The effect of a habitual high cholesterol intake on serum cholesterol and other lipid levels against the background of a moderate fat intake was investigated in 30 rural coloured volunteers (16 men, 14 women) working on an egg farm. Protein contributed approximately 11%, fat 31%, carbohydrate 58% (sucrose 21%) of energy intake. Daily cholesterol intake averaged 575 mg. In men, although not in women, cholesterol intake correlated negatively with serum cholesterol and low-density lipoprotein cholesterol levels, indicating that a high consumption of eggs in the study population did not prejudice lipid homeostasis. The population exhibited a high profile of coronary heart disease risk factors. PMID- 2904180 TI - Islet cell carcinomas of the pancreas: a twenty-year experience. AB - Unlike its lethal exocrine counterpart, islet cell carcinoma of the pancreas is an indolent neuroendocrine neoplasm. The majority of these tumors are hormonally active. When functioning, a number of clinical syndromes (for example, hyperinsulinism, Zollinger-Ellison and Cushing's syndromes) may be evident. Fifty eight patients surgically treated between 1965 and 1984 were retrospectively analyzed. The purpose of this study was to determine the distribution of functioning versus nonfunctioning tumors and the response to type of therapy. Mean postoperative follow-up was 7.4 years. Survival and prognostic indices were calculated by the Kaplan-Meier method and compared with log-rank tests. Of the group, 54% had functioning and 46% nonfunctioning tumors. Gastrinomas were the most common functioning tumors encountered (19%). Of interest was the finding that nonfunctioning tumors increased steadily during the last 15 years of the study (25% to 65%). Curative resections were performed in 15 (26%) and noncurative procedures in 43 patients (74%), with an overall operative mortality rate of 3%. Symptomatic improvement was achieved in 90% (curative) and 51% (noncurative). Survival at 3 years was 87% and 66% for the curative and noncurative groups, respectively (p less than 0.1), with an overall 5-year survival of 42%. The absence of hepatic metastases was a major predictor of survival at 3 years (82% vs 56%, p less than 0.05). Survival was statistically better at 3 years in those patients with gastrinomas compared with patients with nonfunctioning tumors (91% vs 58%, p less than 0.05). Although surgical cure is rare, significant long-term palliation may be achieved in a large percentage of patients with an aggressive surgical approach, occasional total gastrectomy, combination chemotherapy, H2 blockade, when indicated, and, most recently, with the new long-acting analogue of somatostatin. PMID- 2904181 TI - Pancreastatin: a novel peptide inhibitor of parietal cell secretion. AB - Pancreastatin is a recently identified 49-amino-acid peptide found in gastrointestinal tract and gastric mucosa. Its biologic effects on gastric function are unknown. The aim of this study was to determine the effects of pancreastatin [33-49] (the synthetic C-terminal fragment) on acid secretion and somatostatin release in vitro. Isolated rabbit gastric glands were prepared by means of collagenase digestion. Acid secretion was assessed indirectly with use of 14C-aminopyrine (AP) uptake by glands, and somatostatin release from D cells was measured with radioimmunoassay. Pancreastatin alone (10(-10) to 10(-6) mol/L) had no effect on 14C-AP uptake compared with unstimulated glands. In contrast, pancreastatin inhibited with histamine-(10(-6), 10(-5) mol/L; p less than 0.005) and carbachol-(10(-5), 10(-4) mol/L; p less than 0.001) stimulated 14C-AP uptake in a dose-dependent manner. Neither forskolin-(10(-6), 10(-4) mol/L; p greater than 0.50) or 8-Br-cAMP-(10(-5), 10(-4) mol/L; p greater than 0.30) stimulated 14C-AP uptake were influenced by pancreastatin. Pancreastatin had no effect on somatostatin release from glands. These data suggest that pancreastatin probably acts at receptor or membrane level, inhibiting both histamine- and carbachol stimulated 14C-AP uptake. These effects are not mediated by D cell somatostatin release. It is possible that pancreastatin acts as a paracrine or endocrine inhibitory regulator of parietal cell secretion. PMID- 2904182 TI - A prospective study of perioperative and postoperative control of acid hypersecretion in patients with Zollinger-Ellison syndrome undergoing gastrinoma resection. AB - Fifty-five consecutive patients with Zollinger-Ellison syndrome who underwent exploratory laparotomies for gastrinoma resection were evaluated prospectively to determine the effect of gastrinoma resection on acid secretion and to establish criteria for safe and effective perioperative management of gastric acid hypersecretion. In 15 patients (27%) no tumor was found and postoperative serum gastrin, basal acid output (BAO), and maximal acid output (MAO) were unchanged. Twenty-one patients (38%) had gastrinomas resected and were biochemically cured. Median fasting gastrin, median delta secretin, mean BAO, and mean MAO decreased 89%, 94%, 80%, and 43%, respectively, at 3-month follow-up in these patients. In 19 patients gastrinomas were resected, but patients were not cured, and median fasting gastrin, median delta secretin, mean BAO, and mean MAO decreased 47%, 10%, 26%, and 25%, respectively. Forty percent of patients with gastrinoma resected and cured and 81% of patients with gastrinoma resected but not cured continued to hypersecrete acid (BAO greater than 10 mEq/hr) at 3- to 6-month follow-up. Acid control was managed perioperatively during gastrinoma resection by continuous intravenous infusion of H2 receptor antagonists at a dose established by preoperative titration to decrease acid output to less than 10 mEq/hr. Thirty patients were treated with cimetidine at a mean dose of 3.2 mg/kg/hr for a mean of 13.8 days. Twenty-one patients were treated with ranitidine at a mean dose of 1.1 mg/kg/hr for a mean of 8 days. No patients suffered any complications related to acid hypersecretion or side effects of the H2 antagonists. Patients undergoing gastrinoma resection can be managed safely by continuous infusion of H2 antagonists. Successful gastrinoma resection can reduce acid output, but even 40% of biochemically cured patients will continue to hypersecrete acid at short-term follow-up and will require continuation of antisecretory medication. PMID- 2904183 TI - Salmeterol, a new long acting inhaled beta 2 adrenoceptor agonist: comparison with salbutamol in adult asthmatic patients. AB - Salmeterol is a new inhaled beta 2 adrenoceptor agonist, which has been shown in animal experiments to produce a more prolonged bronchodilator effect than currently available beta 2 adrenoceptor agonists. It was studied in eight adult asthmatic patients. Each patient received on separate test days salbutamol 200 micrograms and salmeterol 50, 100, and 200 micrograms according to a randomised, double blind, crossover design. FEV1, peak expiratory flow (PEF), heart rate, blood pressure, and tremor were recorded in the clinic for six hours after drug inhalation; PEF was recorded for a further six hours at home. All three doses of salmeterol produced peak increases in FEV1 (mean 0.5-0.8 l) and PEF (71-100 l/min) similar to those produced by salbutamol 200 micrograms (0.5 l and 74 l/min). After salbutamol FEV1 and PEF had returned to baseline within six hours, but after all three doses of salmeterol more than half of the maximum bronchodilator effect remained after 12 hours. The effects of salbutamol and the two lower doses of salmeterol (50 and 100 micrograms) on cardiovascular measurements and on tremor were similar, whereas after salmeterol 200 micrograms there was a small decrease in diastolic blood pressure and an increase in heart rate and tremor. Thus inhaled salmeterol has a long acting bronchodilator action in asthmatic patients. This effect may be of value in the treatment of asthma, particularly in patients with nocturnal symptoms. PMID- 2904184 TI - Segregation of HLA-DR, -DQ and -DP phenotypes and restriction fragment length polymorphic fragments in two recombinant families. AB - Members of two families were typed for HLA-DR, -DQ and -DP specificities by means of sera and local PLT bulk reagents. One B:C and one DR:DP cross-over were identified in both families. The restriction fragment length polymorphism (RFLP) was analyzed by southern blotting and the use of DR beta, DR alpha, DQ beta, DQ alpha, DP beta and DP alpha probes. Previous observations concerning typical RFLP patterns for serological DR/DQ- and cellular DP-specificities were confirmed. With respect to recombinant haplotypes, RFLP was informative in both families. All polymorphic fragments-(DRB, DQA and B as well as DPA and B)-segregated together in the HLA-B:DR cross-overs. In the DR:DP recombinant children, the DR and DQ fragments were separated from DP fragments, demonstrating that DP-types as defined by PLT and RFLP map close together. No cross-hybridization between the segregating fragments was detected with the various probes. PMID- 2904185 TI - Effect of T cell supplementation to fetal liver cells transplanted into isogeneic mice. PMID- 2904186 TI - Radiation sensitivity of transplanted bone marrow cells. PMID- 2904187 TI - Foot trauma due to rodents in Sierra Leone. PMID- 2904188 TI - Fully automated TV-image analysis of the cell-cycle: comparison of the PLM method with determinations of the percentage and the DNA content of labelled cells. AB - A cell-cycle analysis based on a fully automated TV-image scanning system is proposed to replace the laborious PLM method. To compare the efficiency of the two procedures, cell-cycle parameters were assessed in Ehrlich (diploid and hyperdiploid), L-1210, and JB-1 mouse ascites tumours and in rat jejunal crypts. The percentages of labelled mitoses (PLM) were counted visually on Feulgen stained autoradiographs obtained at various times after a single 3H-thymidine pulse. The fraction of labelled cells (P) and the DNA ratio of labelled and unlabelled cells were measured by TV-image analysis in the same slides and plotted against time. Within practical limits, TV-image analysis using the P curve gives the same results as the PLM method. Using the P-curve has the important advantage that its first part, beginning at the time of 3H-thymidine injection and ending at the first maximum, furnishes more information about the cell cycle than the corresponding part of the PLM curve. It can be used to compute tG2M tS and the ratio of the growth faction index to the cell-cycle time (IP/tC) whereas the first part of the PLM-curve reveals only the length of the S phase (tS). The IP/tC ratio is a readily accessible measure of growth and increases when the cells divide more frequently. Cell death rates may be neglected since the ratio is determined within less than the duration of one cell cycle. Moreover, the data from the first part of the P curve indicate whether there is a large non-growth fraction. If the non-growth fraction is small, i.e. if IP approximately 1, the P curve need only be measured until the first maximum is reached so that fewer samples and animals are required. If the non-growth fraction is large or unknown, the cell-cycle parameters are calculated by reference to the position and size not only of the first minimum and the first maximum, but also of the second minimum of the P curve. PMID- 2904189 TI - Modulating influence of dehydroepiandrosterone administration on the morphology and enzyme phenotype of dimethylaminoazobenzene-induced hepatocellular foci and nodules. AB - The effect o 4 weeks dietary administration of the hormone dehydroepiandrosterone (DHEA) on enzyme and morphological phenotype of focal lesions previously induced by dimethylaminoazobenzene (DAB) treatment was investigated in Sprague-Dawley rats. In contrast to the DAB-alone livers where large numbers of glycogen storing, mixed cell nodules homogeneously positive for glutathione S-transferase P form (GST-P) were apparent, DHEA treated animals were characterized by significantly fewer, more heterogeneous lesions, in some cases demonstrating increased amphophilia and structured basophilia. The enhanced heterogeneity, in some ways reminiscent of that reported earlier for 'reversibility' or 'remodelling' of rapidly induced nodular lesions, was associated with increased catalase (CAT), acid phosphatase (AP) and glucose-6- phosphatase (G6Pase) and decreased glycogen contents and phosphorylase (PHO) activity in both nodules and background parenchyma. Glucose-6-phosphatase (G6PD) activity was elevated irregularly focal lesions also demonstrating a heterogeneous reaction. The experimental data suggest two separate effects of the hormone treatment the first involving modulation of the usual altered phenotype of preneoplastic lesions with a shift towards 'tigroid' cell character and the second, similar to that reported earlier for rapidly induced nodules, involving enhanced phenotypic instability and leading to reduction in numbers. PMID- 2904190 TI - Collagen degradation in the rabbit skin during short-term tissue culture. AB - Full thickness rabbit skin explants were cultured on plastic dish for 1 week and the sequential morphological changes were examined daily by light and electron microscopy. During the cultured period, bundles of dermal collagen fibres gradually loosened and were removed from the upper dermis and from the cut margin of the explant, which was covered by a sheet of migrating epidermal cells. In these areas, cells containing phagocytosed collagen fibrils were observed from the 3rd day to the end of the culture period. These cells containing phagocytosed collagen fibrils included dermal fibroblasts and macrophages, epidermal keratinocytes and endothelial cells lining blood vessels. The presence of acid phosphatase activity in vacuoles containing the collagen fibrils suggested that intracellular degradation of collagen was occurring. In addition, extracellular collagen degradation was recognized around fibroblasts and beneath the migrating epidermis by the high collagenolytic activity at these sites. These findings suggest that both intra- and extracellular collagen degradation may participate in collagen removal from dermal connective tissue in cultured skin explants. PMID- 2904191 TI - Oncogene expression in endocrine pancreatic tumors. AB - The mRNA expression of the (proto)oncogenes Ha-ras, Ki-ras, fos, c-myc, N-myc, and sis was studied in five pancreatic endocrine tumors and two non-neoplastic pancreatic tissues. Compared with non-tumorous pancreatic tissue, Ha-ras and Ki ras mRNA was overexpressed up to 42-fold in all the tumors; metastasizing tumors showed 2-6 times higher Ha-ras mRNA levels than benign neoplasias. In contrast, c myc mRNA levels were higher in normal tissue than n tumors and fos mRNA levels did not differ significantly between tumors and normal tissue. The activities of Ki-ras, fos and c-myc mRNA expression did not correlate with any of the histological or biological properties of the tumors, nor with the clinical course of disease. Our results, although based on a limited number of cases, suggest tha Ha-ras and Ki-ras mRNA overexpression is associated with the development of pancreatic endocrine tumors. The measurement of Ha-ras mRNA levels may contribute to the assessment of tumor prognosis. PMID- 2904192 TI - Regulation of protein turnover versus growth state. III. Growth cessation is associated with activation of autophagy in Yoshida ascites hepatoma AH-340. AB - Yoshida AH-130 ascites hepatoma cells were grown in rats and were examined by quantitative electron microscopy 4 days (exponential growth phase) and 10 days (stationary phase) after intraperitoneal inoculation. No significant differences between growing and growth-inhibited tumors were found in the composition of the cytoplasm, except for a slight increase in the cytoplasm, except for a slight increase in the volume fraction of mitochondria (from 9.6 to 12.1%) and, in particular, a prominent (4.2-fold) increase in the volume fraction of early stage of autophagic vacuoles (from 0.31 x 10(-4) at day 4 to 1.37 x 10(-4) at day 10; P less than 0.001). At the same time, the rate of cell protein degradation was increased twofold, namely from 0.67%/h at day 4 to 1.37%/h at day 10, as measured in vitro after labeling cells with 3H-leucine in vivo. Such elevated proteolytic activity was entirely suppressed by ammonia, which inhibits the lysosomal pathway for protein degradation. The data show that: (i) the regulation of autophagic degradation of cytoplasmic constituents depending on the growth state was maintained in these tumor cells, and (ii) the increase in autophagy measured by morphometric analysis contributed to, yet did not quantitatively explain, the acceleration of protein degradation characterizing the transition from the logarithmic growth phase to the growth-inhibited state. PMID- 2904193 TI - Immunohistochemical studies in human thymomas. Localization of thymosin and various cell marker. AB - Forty five human thymomas were studied immunohistochemically using antibodies to thymosin x-1, thymosin beta-3, cortical epithelium of human thymus (UH-1), mouse thymic nurse cells (Th-3) and Leu-7. Most thymomas were found to contain thymosin x-1 (80%) and thymosin beta-3 (89%). Also used in the study were a new monoclonal antibody (UH-1), which reacts with the epithelial cells forming a meshwork in the cortex of the normal newborn thymus and Leu 7, which reacts with subcapsular epithelial cells in the outer thymic cortex. The combined use of UH-1 and Leu-7 was found to identify neoplastic epithelial cells of thymic cortical origin in thymomas. Approximately 80% (37/45) of the thymomas in the present study reacted with Leu-7, UH-1 or both antibodies, and were thus considered to be derived from cortical thymic epithelium. Of the eight thymomas which were negative with both Leu-7 and UH-1, four were histologically of mixed type characterized by the formation of epithelial cell islands. All four of these thymomas were positive with thymosin and were therefore considered to be of medullary origin. Ten of the thymoma were associated with myasthenia gravis; all were positive with UH-1 and were consider to be of cortical origin. PMID- 2904194 TI - [Suppressive action of the influenza virus on the bone marrow stem cells of mice]. AB - The effect of pathogenic and noninfectious influenza viruses with different surface antigens on colony-forming stem cells of (CBA X C57BL/6)F1 mice was studied. Bone marrow cells were infected with A/PR8/34 (H1N1)/A/Krasnodar/101/59 (H2N2) viruses, a recombinant A/PK-6-3 (H2N1) strain thereof, A/Khabarovsk/933/77 (H1N1) strain; then they were inoculated intravenously to irradiated (820 rad) syngeneic recipients, and colony-forming units (CFU) were determined in the spleens 9 days after injection. Inoculation of bone marrow cells (2 X 10(5) per mouse) to the irradiated recipients immediately after mixing with a live A/Krasnodar virus heated at 56 degrees C, live A/PK-6-3, and A/Khabarovsk viruses resulted in suppression of formation of CFU and marked atrophy of the recipients' spleens. There was no suppression after the use in these experiments of the pathogenic A/PR/8/34 strain. Inhibition of CFU production in the spleen was observed after inoculation of the recipients with bone marrow cells incubated for 1 hour at 37 degrees C with A/PR/8/34, A/Krasnodar/101/59 viruses and the recombinant strain. Possible mechanisms of the suppressive effect of influenza A virus on CFU production in mice are discussed. PMID- 2904195 TI - [Integration mechanisms and morphogenesis (the problem of the evolution of ontogeny)]. PMID- 2904196 TI - Bacteriophages of Bordetella sp.: features of lysogeny and conversion. AB - It has been the purpose of this paper to study molecular-biological features of the Bordetella bacteriophage interaction with the host cell during lysogeny and conversion as well as to determine the degree of homology between genomes of homologous and heterologous bacteriophages. Genomes of bacteriophages from B. pertussis 134, 41405 and B. bronchiseptica 214 were studied. Heteroduplex and restriction analyses revealed a heterogeneity of bacteriophage populations, and their DNAs were found to differ in size and position of inserts. As shown by blot hybridization, the bacteriophage genome is not inserted into the chromosome of the lysogenic cell but apparently exists as an autonomous plasmid replicon. It has been established that during conversion only a part of the phage genome is inserted into the chromosome of the recipient cell. PMID- 2904197 TI - All species of the genus Bordetella contain genes for pertussis toxin of Bordetella pertussis. AB - A molecular probe for the PT-operon of B. pertussis hybridized with 4.7 Kb EcoRI fragments of chromosomal DNAs of B. pertussis strain 475 phase I, phase IV, B. parapertussis strains 504 and 17903, B. bronchiseptica strain 214, B. parapertussis strain 17903-convertant of B. pertussis phage 134 but not with phage 134 DNA under stringent conditions of DNA-DNA hybridization. This fact indicates the presence of PT-genes in all Bordetella species. Since there is no production of PT in B. parapertussis and B. bronchiseptica, a presence of regulatory mutations in the PT-operon or absence of the functionally active vir gene product in these species is suggested. PMID- 2904198 TI - Relative cell surface hydrophobicity of Escherichia coli strains with various recognized fimbrial antigens and without recognized fimbriae. AB - Bacterial surface hydrophobicity as well as mannose-sensitive haemagglutinating (MSHA) and mannose-resistant haemagglutinating (MRHA) activities were studied in Escherichia coli strains with and without recognized fimbrial antigens grown under different conditions. Relative bacterial surface hydrophobicity was measured by the salt aggregation test. Four kinds of bacterial aggregations depending on fimbrial antigens were observed: bacteria with CFA/I, CFA/II, CFA/III and K88 aggregated in a particulated form, bacteria with type 1 pilus in a granular form, and bacteria with K99 in a tiny granular form. Some strains, mainly when grown under non-optimal conditions at 18 degrees C or when heated at 80 degrees C, aggregated in a non-typical filamentous form. Among MRHA- MSHA+ (type 1 pilus positive), two classes of bacteria were detected: hydrophobic bacteria aggregating in 0.2-0.4 M ammonium sulphate, and non-hydrophobic bacteria aggregating in 2.0 to 1.6 M ammonium sulphate. The hydrophobicity levels in strains possessing different recognized fimbrial antigens, when grown under optimal conditions to express fimbriae and their typical haemagglutination pattern, were of a decreasing order, viz. CFA/III = CFA/I greater than CFA/II greater than MRHA-MSHA+ hydrophobic = MRHA+ greater than P987 greater than K99 F41 = K88 greater than MRHA- MSHA+ non-hydrophobic greater than MRHA- MSHA- without recognized fimbriae. PMID- 2904199 TI - [Effect of histamine on the rosette-forming capacity of T-lymphocytes in immunization with ADPT vaccine and its components]. AB - The results obtained in the study of the influence of histamine on the capacity of T-lymphocytes of guinea pigs immunized with DPT-vaccine and its components for spontaneous rosette formation are presented. Histamine at a concentration of 10( 3) M has been found to inhibit the capacity of blood and splenic lymphocytes of guinea pigs immunized with adsorbed DPT vaccine for spontaneous rosette formation. The inhibitory effect is more pronounced after the immunization of the animals with adsorbed DPT vaccine and Bordetella pertussis suspension. PMID- 2904200 TI - [Pili (fimbriae) of the causative agents of plague and pseudotuberculosis: their detection in the hemagglutination reaction, the passive hemagglutination reaction and in an immunoenzyme analysis system]. AB - Newly developed serological methods for the detection of pili in the passive hemagglutination (PHA) test with the use of immunoglobulin erythrocytic diagnosticum and in the enzyme immunoassay (EIA) with the use of specific immunoglobulins labeled with horse radish peroxidase have been found to exceed the method of detecting pili, based on the determination of their hemagglutinating activity, in sensitivity and specificity. Besides, the PHA test and EIA have proved to be capable of detecting low molecular fragments of pili, obtained by sonication and having lost their hemagglutinating activity. PMID- 2904201 TI - [Physicochemical and biological characteristics of preparations of an antigenic complex isolated from the cultivation medium of Bordetella pertussis]. AB - The physicochemical and biological properties of antigenic complexes isolated from the supernatant fluid of the culture medium of B. pertussis, strains 305 and 475, were studied. The preparations obtained from both strains contained proteins, carbohydrates, nucleic acids and lipids. Electrophoresis in polyacrylamide gel revealed the presence of filamentous hemagglutinin, 4 subunits of B. pertussis toxin and agglutinogens in the antigenic complexes of both strains. The preparations of both strains possessed similar toxic properties and, after their detoxification, produced a pronounced protective effect. PMID- 2904202 TI - Nerve fibers showing immunoreactivities for thyrosine hydroxylase and dopamine beta-hydroxylase re-appear in the guinea pig uvea after sympathectomy. AB - After sympathectomy we have studied the re-appearance of nerve fibers showing catecholaminergic characteristics in the uvea of the guinea pig. Immunoreactivities for two catecholamine symthetizing enzymes, tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH), were used as markers. Both TH-like and DBH-like immunoreactive nerve fibers disappeared after the extirpation of ipsilateral superior cervical ganglion. In the choroid the TH-like and DBH-like immunoreactive nerve fibers re-appeared within 2 weeks. In the iris and the ciliary body both of these types of immunoreactive nerve fibers re appeared 10 weeks after the denervation. The morphological appearance of these re appearing nerve fibers was not similar to those in the non-denervated uvea. PMID- 2904203 TI - Comparison of topical timolol vs betaxolol on cardiopulmonary exercise performance in healthy volunteers. AB - The effects of topical timolol vs betaxolol on cardiopulmonary exercise performance were studied in a randomised double-masked fashion in 12 healthy male volunteers. Cardiopulmonary parameters were evaluated at the anaerobic threshold and at peak exercise. Intraocular pressure was determined before and after treatment by applanation tonometry. No differences were found in aerobic or peak exercise capacity. Maximal heart rate was slightly lower (P less than 0.05) following treatment with timolol compared with betaxolol. However, a correspondingly higher oxygen pulse (oxygen uptake/heart rate) compensated for this reduction and resulted in no difference in peak performance. At physiological work levels, it was not possible to demonstrate any influence of topical, selective or non-selective, beta-adrenergic blockade on cardiopulmonary exercise performance in these healthy volunteers. PMID- 2904204 TI - The role of hypothalamic hormones in the control of growth hormone secretion and of growth. AB - GHRH and somatostatin have major integrative roles in the control of GH secretion. Alterations in the secretion of each hypothalamic hormone have profound effects on GH secretion. On the basis of current information, it appears that disturbances in GHRH secretion provide a most convincing argument for the pathophysiological role of this hypothalamic hormone in clinically recognized disorders of GH secretion. Thus, the potential use of GHRH and its agonists and antagonists in the treatment of patients with both deficient and excessive GH secretion is based on a solid framework of physiological and pathophysiological studies. PMID- 2904205 TI - [Effects of methyl-4-ethyl-6,7-dimethoxy-beta-carboline-3-carboxylate on the release of monoamine neurotransmitters from rat brain slices]. PMID- 2904206 TI - Selective alpha-adrenoceptor blocking action of melperone. PMID- 2904207 TI - Acupuncture treatment for duodenal ulcer. AB - The effect of acupuncture therapy for duodenal ulcer was investigated in 21 male and female patients. The diagnosis and healing were verified by gastroscopy. It was found that the needle therapy for 3 weeks led to complete recovery in 76 percent of the patients. Diet, alcohol and cigarette abstinency were necessary for healing. Cuti-visceral reflex activation eliciting the improvement of the secretory and motor function of the gastrointestinal tract and effects in the CNS leading to analgesia and tranquilization may play a role in the mechanism of action. Our conclusion is that acupuncture can be satisfactory method to cure duodenal ulcer. PMID- 2904208 TI - Laser photobiostimulation-induced hypoalgesia in rats is not naloxone reversible. AB - Laser photobiostimulation (LPBS) at the pulsing frequency of 4 Hz applied to the low resistance point located at the base of the tail of the rat, (Governing Vessel Meridian 1), produced a hypoalgesic effect, measured by tail-flick and hot plate techniques. Pre-treatment with low dose naloxone (2 mg/kg) did not reverse the hypoalgesic effect of LPBS. High dose naloxone (20 mg/kg) reversed only partially, but significantly, the hypoalgesic effect of LPBS measured by hot plate, but not that measured by the tail-flick technique. These data suggest that mechanisms other than endogenous opioids may be involved in LPBS-induced hypoalgesia. PMID- 2904209 TI - Quantitative analysis of bioelectrical potentials for the diagnosis of internal organ pathology and theoretical speculations concerning electrical circulation in the organism. AB - Over 900 experiments on dogs and 135 clinical investigations of healthy people and patients of psychiatric and cardiological departments were performed. With the aid of a 8-channel biopotential amplifier and integrator, bioelectrical potential (BEP) directly from internal organs or from various skin zones were recorded. The quantitative parameters of the BEP--their square values and the sum of the square values of BEP recorded simultaneously from several points of the organism--were measured. The effect of low (1 Hz) and high (28 GHz) frequency electrical stimulation was studied. The stimulation of spleen, liver, stomach, small intestine and corresponding acupuncture points had the greatest effect on the quantitative parameters of the BEP in stomach and small intestine. During patient investigation, the most remarkable changes of the studied parameters were noticed in the BEP recorded from the acupuncture points of the affected internal organ meridians. The existence of the common points between Eastern medicine and Western science are discussed. The analysis of the BEP quantitative parameters proves the existence of electrophysiological equilibrium parameters in the organism--bioelectrical homeostasis. The possible theories of electrical circulation in the organism and their relations with traditional acupuncture theoretical concepts are also discussed. PMID- 2904210 TI - Microbial infection or trauma at cardiovascular representation area of medulla oblongata as some of the possible causes of hypertension or hypotension. AB - The author found that the onset of hypertension or hypotension is relatively often associated with infections or development of so-called "sneezing due to allergy to pollen or dust," with or without headache, or due to trauma to the occipital area of the head. Using the "Bi-Digital O-ring Test," it was possible to demonstrate that, among bacterial and viral infections, the most common cause of infection associated with the appearance of hypertension is chlamydia, herpes simplex virus, cytomegalovirus, or Epstein-Barr virus. Particularly chlamydia and/or herpes simplex virus, with or without coexistence of other microbes, is usually present at the heart representation area of the medulla oblongata, especially at the left ventricular representation area, often accompanied by upper respiratory infection, cephalic, cervical or facial pain, with or without coexisting genito-urinary infection. The left ventricular representation area of the medulla oblongata is usually located at the right side. In most hypertensive patients, the left ventricular representation area of the medulla oblongata is enlarged up to 3 or 4 times normal size. Sufficient antibiotic treatment of chlamydia with erythromycin sometimes eliminated severe hypertension which appeared after chlamydia infection. In the presence of viral infections, such as herpes simplex, which is also causing severe pain in the head or neck, oral administration of acyclovir, erythromycin, or EPA (Eicosa Pentaenoic acid)-DHA (docosa hexaenoic acid) Omega 3 fish oil often reduced associated intractable pain and hypertension toward the normal level. Thus, the author is proposing new possible mechanisms as among the causes of so-called essential hypertension as a result of microbial infection or trauma of the cardiovascular representation area, particularly that of the left ventricular representation area at the right side of the medulla oblongata. PMID- 2904211 TI - The role of trigeminal nerve in acupuncture. AB - The purpose of this work is to expose the topographoanatomical and functional aspects of trigeminal nerve (TN) on the view of somatotopic representation of acupuncture microsystems, the interaction among the central nervous system, the endocrine system and the immune system via the endorphins and enkephalins. In order to establish the structural and functional relationships between the TN, acupuncture points and zones on the head and neck regions; the following has been done: 1) Identification of number of acupuncture points and zones, comparing with other localization; 2) the analysis of volume of diagnostic and therapeutic indications of about 20,000 patients treating and 662 patients operated by acupuncture; and 3) the analysis of sensory somatotopic cortical representation of the TN. Our research confirmed the role of TN in acupuncture microsystems and we expect it to play this role in the future also. PMID- 2904212 TI - Relationship between acupuncture-induced immunity and the regulation of central neurotransmitters in the rabbit: I. Effect of central catecholaminergic neurons in regulating acupuncture-induced immune function. AB - The central catecholaminergic neurons play an important role in the promotion of the T-lymphocyte transformation and the regulation of the positive rate of acid a naphthylacetate esterase (ANAE) activity with acupuncture. The mechanism by which acupuncture promotes the T-lymphocyte transformation function may be principally by promoting the anabolism of the T-lymphocyte and speeding up the anabolism of the DNA. Judging from the fact that acupuncture increases the positive rate of ANAE, it can be assumed that the quantity of T-lymphocyte was increased markedly. It remains to be clarified what links exist through which the central catecholaminergic neurons can influence the acupuncture induced immunity, and what the effect of other transmitter neurons of the central nervous system are on acupuncture induced immunity. PMID- 2904213 TI - Studies on the enhanced effect of acupuncture analgesia and acupuncture anesthesia by D-phenylalanine (first report)--effect on pain threshold and inhibition by naloxone. AB - It has been claimed that the mechanism of acupuncture analgesia can be explained in part by endogenous opioids. If so, it might be possible to enhance the analgesic effect of acupuncture by the administration of endorphins. If D phenylalanine (DPA), an inhibitor of the endorphin degrading enzyme, is administered, the analgesic effect of acupuncture should be prolonged due to the increased level of endorphins. From the changes of the pain threshold (PT), we investigated whether or not the pre-administration of DPA can enhance the analgesic effect of acupuncture in humans. In addition, we examined the inhibitory effect of naloxone. 1) In all five subjects whose PT was raised after acupuncture anesthesia (respondents), the rise in PT was significantly prolonged by DPA. 2) Out of 10 subjects whose PT remained almost unchanged after acupuncture anesthesia (non-respondents), the PT was increased by DPA in 5 cases. 3) The rise in PT was most prominent when DPA was administered 30 minutes before the start of acupuncture anesthesia. 4) In all 4 respondents in whom the rise in PT persisted after DPA and acupuncture anesthesia, their raised PT dropped after the intravenous injection of naloxone (10 mg). 5) These findings show that DPA enhances the analgesic effect of acupuncture by the "endorphin mechanism." PMID- 2904215 TI - When not to use ipecac. PMID- 2904214 TI - Effect of low power laser irradiation on nociceptive cells in Hirudo medicinalis. AB - The effect of low power Helium-Neon (He-Ne) and Gallium-Arsenide (Ga-As) laser on the nociceptors in Hirudo medicinalis was studied. The results show that low power laser irradiation does not: affect the membrane potential or the excitability of the nociceptive neurons, affect the mechanical pressure required to activate the nociceptors or their action potentials. The results indicate that the analgesic effects reported in humans with "laser-acupuncture" with similar modes of low power laser are likely not explained by effects on nervous tissue. PMID- 2904216 TI - Systemic and coronary hemodynamic and neurohumoral effects of levodopa in chronic congestive heart failure. AB - Systemic and neurohumoral effects of oral levodopa were evaluated in 17 patients with severe chronic heart failure. The maximum mean dopamine level achieved after 1.5 g of oral levodopa was 19.6 +/- 16.4 ng/ml. At peak dopamine level, cardiac index increased by 14% from baseline (1.95 +/- 0.55 to 2.27 +/- 0.45 liters/min/m2, p less than 0.05), stroke volume index increased by 14% (22.4 +/- 6.0 to 25.9 +/- 5.8 ml/min/m2, p less than 0.01). There was a trend toward reduced systemic vascular resistance of 13% (1,773 +/- 769 to 1,535 +/- 432 dynes.s.cm-5, p = 0.08). There was no significant change from baseline in heart rate, mean arterial pressure, right atrial pressure, pulmonary capillary wedge pressure, pulmonary vascular resistance and rate-pressure product. In addition, as the arterial dopamine level increased there was a concomitant decrease in plasma norepinephrine level that was sustained for the period of observation. In a subgroup of 8 patients, there was no change in coronary sinus blood flow, myocardial oxygen consumption, myocardial oxygen extraction, lactate extraction and transmyocardial release of catecholamines after levodopa. These findings suggest that oral levodopa, 1.5 g, can improve left ventricular function without adversely affecting myocardial energetics and catecholamine balance. PMID- 2904217 TI - Increased cytosol aminopeptidase and lactate dehydrogenase in serum originating from lymphocytes in measles and rubella infection. AB - We determined cytosol aminopeptidase (c-AP; EC 3.4.11.1) and lactate dehydrogenase (LDH) levels in serum; these enzymes are known to originate from lymphocytes in patients with measles and rubella. In patients with measles (n = 19), both enzyme levels increased markedly with the onset of rash: mean (+/- SD) c-AP was 269.7 +/- 103.5 U/L and LDH was 1149.5 +/- 255.2 U/L. In patients with rubella, activities of both enzymes increased mildly: c-AP (n = 18) was 81.6 +/- 24.4 U/L and LDH (n = 13) was 674.0 +/- 168.8 U/L. Increased c-AP and LDH levels in patients with measles and rubella presumably originate from the destruction of infected, activated lymphocytes, especially T lymphocytes. PMID- 2904218 TI - Do anticholinergics interact with histamine H2 receptor antagonists on night intragastric acidity in active duodenal ulcer patients? AB - The effect of administering low doses of famotidine or ranitidine alone or in combination with an M1-receptor-selective antagonist, pirenzepine, on night intragastric acidity was evaluated in 16 active duodenal ulcer patients to verify 1) whether anticholinergics and H2-antagonists have a synergic effect on inhibition of night gastric acidity, and 2) whether patients with vagal hypertone are more sensitive to anticholinergics than the remainder of the duodenal ulcer population. The endogastric pH was continuously recorded for 12 h (8 PM-8 AM) after random, single-blind administration of one of the following drug regimens: 20 mg famotidine, 150 mg ranitidine, 50 mg pirenzepine, 20 mg famotidine plus 50 mg pirenzepine, and 150 mg ranitidine plus 50 mg pirenzepine. Six patients with a basal acid output:peak acid output BAO:PAO greater than 0.3 were considered "vagal hypertone" subjects. Night gastric acidity inhibition was -39.6% with pirenzepine (p less than 0.001) and -73.7% and -71.5% with famotidine or ranitidine (p less than 0.001 vs. pirenzepine). The simultaneous administration of pirenzepine with famotidine or ranitidine provoked only a slight, insignificant increase in percent suppression, 5.1% and 6.3%, respectively, and did not modify either the time lag to onset of anti-H2 action or the duration of action. Patients with a BAO:PAO greater than 0.3 were not more sensitive to anticholinergic treatment than other duodenal ulcer patients. Our study furnishes evidence that combined administration of anti-H2 and anticholinergics is not significantly better than anti-H2 alone, in active duodenal ulcer patients. PMID- 2904219 TI - Response to "H2-receptor antagonists and duodenal ulcer recurrence". PMID- 2904220 TI - New approach for isolation of VNTR markers. AB - Elsewhere we have reported an efficient method for isolating VNTR (Variable Number of Tandem Repeats) markers. Several of the VNTR markers isolated in those experiments were sequenced, and a DNA sequence of 9 bp (GNNGTGGG) emerged as an apparent consensus sequence for VNTR markers. To confirm this result and to develop more VNTR markers, we synthesized nine different 18-base-long oligonucleotides whose sequences each included GNNGTGGG. When 102 cosmid clones selected by these oligonucleotides were tested for polymorphism, 34 (33%) of them showed multiallelic VNTR polymorphisms (average heterozygosity 68%). This procedure represents a new and efficient approach for isolating additional VNTR markers and supports the idea that the GNNGTGGG sequence may play an important role in the generation of the multiallelic systems within the human genome. PMID- 2904221 TI - Clinical and molecular heterogeneity of phenylalanine hydroxylase deficiencies in France. AB - RFLPs of 68 normal and 74 mutant alleles at the phenylalanine hydroxylase (PAH) locus were determined in 37 French kindreds. A total of 23 haplotypes, including 18 normal and 16 mutant alleles, were observed. Two-thirds of all mutant alleles were confined within only four haplotypes, while the last third was accounted for by 12 haplotypes, including eight haplotypes absent from Caucasian pedigrees reported thus far. Several mutant haplotypes were present in typical phenylketonuria only, others were present in variants only, and some were present in both. In addition, a particular mutant haplotype (haplotype 2) was found to harbor different mutations in our series, resulting in either typical phenylketonuria or in mild hyperphenylalaninemias. The diploid combination of so many mutant haplotypes in PAH-deficient patients and of compound heterozygosity at the PAH locus in southern Europe might account for the broad spectrum of individual phenotypes observed in France. PMID- 2904222 TI - HLA-DR typing "at the DNA level": RFLPs and subtypes detected with a DR beta cDNA probe. AB - The HLA-DR beta gene, used as a hybridization probe, detects RFLPs that correlate with HLA-DR specificities. Using genomic DNA from more than 200 individuals, we have carried out a population study with a cDNA probe for the DR beta chain, which, under appropriate conditions, does not cross-hybridize with genes from other HLA-D subregions (e.g., DP and DQ). We first assessed the correspondence between serologically defined HLA-DR types and DNA patterns obtained after digestion with TaqI and found that DNA patterns allowed us to identify most specificities. Only two pairs of antigens are not distinguishable: with the DR beta probe alone we cannot distinguish DR3 from DRw6 or DR7 from DRw9. However, the correct assignment can always be made for the first pair by hybridizing the same digests with a DQ alpha or DQ beta probe. Thus DR typing from the DNA patterns is practical and accurate. We also looked for serologically undetectable subtypes. RFLPs revealed high-frequency subtypes for the specificities DR 2, 3, 5, w6, 7, and w9. Some of these are more accurately viewed as variant haplotypes, since the relevant variation is probably not at the DR beta locus that determines the serological specificities but rather at other closely linked and highly homologous DR beta loci such as DR beta-III. Nevertheless, the existence of variant haplotypes for so many specificities indicates a wealth of polymorphic variation beyond that detected serologically and provides more specific markers for studies of various diseases associated with HLA-DR specificities. PMID- 2904223 TI - DNA haplotyping of PI Z and M alleles within the German population. PMID- 2904224 TI - Impotence in diabetic men. AB - Studies relating to pathogenetic mechanisms resulting in impotence in diabetic subjects have been reviewed. Erectile dysfunction was reported to occur in 50 to 75 percent of diabetic patients and the prevalence appeared to increase with age. Contributions of vascular, endocrine, and neurologic system alterations result in this disturbing condition, but a detailed analysis of all the parameters was not found in any individual study. In our review of 301 veterans presenting to a sexual dysfunction clinic, the clinical and hormonal alterations in the diabetic patients closely resemble those seen in nondiabetic impotent subjects. Atherosclerotic vascular changes play an important predisposing role in the development of impotence. A difference exists between the prevalences of associated medical conditions in diabetic patients taking insulin, compared with those receiving oral agents or receiving dietary management. The high prevalence of impotence in diabetic patients seems to be due to the high prevalence of its vascular complications. Considering the availability of useful therapeutic approaches, it is mandatory to evaluate all diabetic men for the presence of impotence. PMID- 2904225 TI - Adult T-cell leukemia associated with HTLV-I and simultaneous infection by human immunodeficiency virus type 2 and human herpesvirus 6 in an African woman: a clinical, virologic, and familial serologic study. PMID- 2904226 TI - Protracted neuroleptic malignant syndrome complicating long-acting neuroleptic administration. PMID- 2904228 TI - Issues of treatment efficacy in legal proceedings. PMID- 2904227 TI - Critical review of liability for benzodiazepine abuse among alcoholics. AB - The authors critically reviewed the literature on benzodiazepine use among alcoholics, psychiatric patients, and the general population to determine whether alcoholics have a greater liability for benzodiazepine abuse. Data suggest that the prevalence of benzodiazepine use among alcoholics is greater than in the general population but comparable to the prevalence in psychiatric patients. The liability for abuse may also be greater for alcoholics, but the substantial methodologic deficiencies of existing studies preclude such a conclusion. Given the frequency of anxiety disorders and benzodiazepine use among alcoholics, their potential for benzodiazepine abuse is an important issue. The authors discuss clinical guidelines and strategies for future research. PMID- 2904229 TI - Amebic liver abscess and circulating immune complexes of Entamoeba histolytica proteins. AB - An enzyme-linked immunosorbent assay (ELISA) has been developed to detect amebic antigen in polyethylene-glycol-precipitable circulating immune complexes. Seventy nine percent of 191 patients with amebic liver abscesses and 46% of 26 Entamoeba histolytica cyst passers had positive tests. None of the samples from 43 apparently healthy controls, 8 patients with past amebic liver abscesses or 31 patients with Giardia lamblia infections were positive. One patient out of 32 with viral hepatitis and 1 patient out of 27 with intestinal tuberculosis had positive tests. PMID- 2904230 TI - [2 forms of antigamete immunity in infertility of inflammatory origin and the level of regulatory T-lymphocytes]. PMID- 2904231 TI - Hormonal regulation of rat testicular gamma-glutamyl-transpeptidase "in vivo" and "in vitro". AB - The hormonal regulation of gamma-glutamyl transpeptidase (gamma-GTP), an enzyme marker of Sertoli cells, was studied in immature rats that received 50 micrograms/day of testosterone propionate (TP) during 6 days to suppress pituitary LH and FSH. Suppression of LH was monitored indirectly by the determination of intratesticular levels of testosterone and suppression of FSH by radioimmunoassay of serum FSH. Enzyme activity in the testis decreased in parallel to intratesticular testosterone suppression, and it did recover up to control values when animals received 500 micrograms/day of TP, a dose that was able to maintain intratesticular testosterone at normal levels. beta glucuronidase, another enzyme marker of Sertoli cells, was not affected by these treatments. A significant decrease in gamma-GTP was detected 24h after significant suppression of intratesticular testosterone and it returned to control levels 2 days after increasing the dose of TP to 500 micrograms/day. Administration of FSH to rats with depletion of intratesticular testosterone was able to maintain testicular gamma-GTP at control levels. An stimulatory action of FSH could also be demonstrated in primary Sertoli cell cultures. It is concluded that testicular gamma-GTP is under the regulation of both androgens and FSH while beta-glucuronidase is not. Eventhough the function of gamma-GTP in the testis is not known, the key role that it plays in other tissues suggests that it might be important in the regulation of Sertoli cell-germ cell interactions. PMID- 2904232 TI - Pharmacodynamics of vecuronium and atracurium in the obese surgical patient. AB - The effect of obesity on the duration of action of the nondepolarizing muscle relaxants atracurium and vecuronium was studied in 28 neurosurgical patients. In obese patients given vecuronium (0.1 mg/kg), the time to go from 5 to 25% of recovery of twitch response was statistically significantly longer (14.6 +/- 7 minutes, mean +/- SD) than it was in nonobese control patients (6.9 +/- 2 minutes). Similarly, with vecuronium times for recovery from 25 to 75% were longer (33 +/- 15 minutes) in obese patients than in control patients (13.2 +/- 2 minutes), as was time to 75% recovery, 82 +/- 30 minutes in obese patients, 50 +/ 9 minutes in controls. In contrast, obese patients given atracurium (0.5 mg/kg) exhibited no difference in recovery indexes or recovery times when compared to control patients of normal weight. The prolonged duration of action of vecuronium in obese patients is most likely related to impaired hepatic clearance and/or an overdose effect with recovery occurring during the distribution phase. That the duration of action of atracurium is not prolonged in the obese is believed due to this relaxant's not depending on organ function for elimination. PMID- 2904233 TI - The effect of maintenance dose vecuronium on pre-established metocurine- or vecuronium-induced neuromuscular blockade. PMID- 2904234 TI - An alternative method of paralysis for rapid-sequence induction. PMID- 2904235 TI - Periarteritis with intra-abdominal bleeding. PMID- 2904236 TI - Effect of nipradilol, a new beta-blocker, on leukotriene D4-induced contraction in guinea pig tracheal smooth muscle. AB - The relaxant effect on smooth muscle of nitro compounds is suggested to be linked with the increase in the tissue level of cyclic GMP by activating guanylate cyclase. In this study, we investigated the effects of nipradilol, a new beta blocker, which has NO2 residue in the molecular structure, and isosorbide dinitrate (ISDN) on guinea pig tracheal smooth muscle in comparison with the effect of propranolol. Nipradilol and ISDN showed dose-dependent relaxant effects on leukotriene (LT) D4-induced contraction of tracheal smooth muscle, though propranolol had no effect. 8-Bromo-cyclic GMP also showed a relaxant effect dose dependently. Nipradilol and ISDN elevated cyclic GMP levels in tracheal tissue dose dependently; however, propranolol caused no change in cyclic GMP levels. From these results, it is suggested that nipradilol relaxes LTD4-induced contraction of tracheal smooth muscle by increasing the tissue level of cyclic GMP. PMID- 2904237 TI - Five-year follow-up of a clinical trial of three 6-month regimens of chemotherapy given intermittently in the continuation phase in the treatment of pulmonary tuberculosis. Singapore Tuberculosis Service/British Medical Research Council. AB - In a study in Singapore, patients of Chinese, Malay, and Indian ethnic origin with sputum-smear-positive pulmonary tuberculosis were allocated at random to daily treatment with streptomycin, isoniazid, rifampin, and pyrazinamide for 2 months (2SHRZ), for 1 month (1SHRZ), or for 2 months without streptomycin (2HRZ), followed, for all patients, by 3-times-weekly isoniazid and rifampin (H3 R3) up to 6 months. As previously reported, all except 1 of 319 patients with drug susceptible tubercle bacilli pretreatment had a favorable bacteriologic status at the end of chemotherapy, and among the 300 patients assessed up to 30 months (24 months after the end of chemotherapy), there was only 1 bacteriologic relapse in each series, giving an overall therapeutic failure rate of only 1.3%. Follow-up has been continued at 6-month intervals up to 5 yr. During the 5 yr, the total relapse rate for patients with drug-susceptible strains pretreatment was 2.4% of 297 patients (95% confidence limits, 1.0 to 4.8%). Among the 31 patients with strains resistant to isoniazid, streptomycin, or both drugs pretreatment, there were no failures during chemotherapy and 4 (13%) subsequent relapses. PMID- 2904238 TI - [The inhibition of action. Interdisciplinary approach of its mechanisms and physiopathology]. AB - The author recalls his group's work during the three past decades and how, starting from the study of traumatic states, he established the distinction between shock and stress, physiologically and biologically speaking. According to him, stress supposes a memory process, i.e. the learning of the inefficiency of action in controlling the environmental characteristics. This learning involves cerebral areas and nerve tracks which, as behavioural consequences produce action inhibition. In the neurophysiological field, he underlines the importance, for these mechanisms, of the cortex, dorsal Ammon's horn, lateral tonsil and subthalamic nucleus. He shows why it seems obvious that the mediators of the action inhibiting system are acetylcholine and serotonin. He also recalls the many experimental facts which allow to say that the action inhibiting system is responsible for the release of the hypothalamic-hypophyseal-adrenocortical reaction and of the peripheric sympathetic adrenergic reaction to aggression. He finally shows the function of these two systems where the main pathological accidents originate. He also stresses the discovery and the introduction in the therapeutical paraphernalia of a new molecule minaprine, which he considers as inhibiting action inhibition, and as such, as an indirect anti-depressive drug. The pathology, which is said psychosomatic, thus becomes a pathology of action inhibition, where unconscious memory of past interdictions and failures, relates the subject and his present reaction to environment, to his whole psycho-social past. PMID- 2904239 TI - [Digital necroses induced by beta-blockers]. PMID- 2904240 TI - In vivo metabolism of nitrogen precursors for urea synthesis in the postprandial rat. AB - (1) Adult postprandial rats were given a continuous, intravenous infusion of 15N labelled glutamate, alanine, ammonium chloride and glutamine amide for 6 h. The enrichment in the free hepatic pool was measured for ammonia, glutamine amide, urea, aspartate, glutamate and alanine. (2) Glutamine and glutamate supplied significantly more nitrogen to urea than ammonium chloride or alanine. (3) Glutamate was not a significant source of hepatic ammonia, hence in this situation it is not necessary to impute a major role to glutamate dehydrogenase in hepatic ammoniagenesis for urea synthesis. (4) Glutamine and ammonia, mostly of intestinal origin in the postprandial state, were major precursors of hepatic ammonia. (5) The nitrogen of glutamate and alanine moved to urea primarily through aspartic acid. PMID- 2904241 TI - Reduction of side effects of specific immunotherapy by premedication with antihistaminics and reduction of maximal dosage to 50.000 SQ-U/ml. PMID- 2904242 TI - Physiological regulation of acetyl-CoA carboxylase gene expression: effects of diet, diabetes, and lactation on acetyl-CoA carboxylase mRNA. AB - We measured acetyl-CoA carboxylase mRNA levels in various tissues of the rat under different nutritional and hormonal states using a cDNA probe. We surveyed physiological conditions which are known to alter carboxylase activity, and thus fatty acid synthesis, to determine whether changes in the levels of carboxylase mRNA are involved. The present studies include the effects of fasting and refeeding, diabetes and insulin, and lactation on carboxylase mRNA levels. Northern blot analysis of liver RNA revealed that fasting followed by refeeding animals a fat-free (high carbohydrate) diet dramatically increased the amount of carboxylase mRNA compared to the fasted condition. These changes in the level of mRNA correspond to changes in the activity and amount of acetyl-CoA carboxylase. Acetyl-CoA carboxylase mRNA levels in epididymal fat tissue decreased upon fasting and increased to virtually normal levels after 72 h of refeeding, closely resembling the liver response. The amount of acetyl-CoA carboxylase mRNA decreased markedly in epididymal fat tissue of diabetic rats as compared to nondiabetic animals. However, 6 h after injection of insulin the mRNA level returned to that of the nondiabetic animals. Gestation and lactation also affected the levels of carboxylase mRNA in both liver and mammary gland. Maximum induction in both tissues occurred 5 days postpartum. These studies suggest that these diverse physiological conditions affect fatty acid synthesis in part by altering acetyl-CoA carboxylase gene expression. PMID- 2904243 TI - [Recent progress in non-Hodgkin's lymphoma study in Japan]. AB - Great progress has been made in clinical research on non-Hodgkin's lymphoma during the last 15 years. Surface marker and DNA analyses of immunoglobulin and T cell receptor genes are essential for new classification of the disease according to the cellular origin of tumor cells. This approach resulted in the establishment of new disease entities such as adult T-cell leukemia/lymphoma(ATL), immunoblastic lymphoadenopathy (IBL)-like T-cell lymphoma, and the pleural B-lymphoma occurring in long-standing pyothorax. New retrovirus, HTLV-I, was found during studies on ATL. Prevention of HTLV-I infection is an important project. HTLV-I negative ATL was also found and is of particular interest in understanding leukemogenesis of ATL. An oncogen such as bcl-2 is important for characterization of follicular lymphoma. Prognostic factors of patients with T-lymphoma are completely different from those of B lymphoma. Risk grouping by combination of major prognostic factors is useful for the selection of the best treatment modality and the accurate estimation of prognosis of patients at initial presentation. The effect of combination chemotherapy should be evaluated separately between T- and B-lymphomas because of the difference in response rate and prognostic factors. PMID- 2904244 TI - Plasma testosterone in preterm infants with cryptorchidism. AB - Cryptorchidism is common in infants born preterm, yet the mechanism for its occurrence is still debated. In a study of 21 premature babies with cryptorchidism at 18 months post-term and 21 case matched controls, cryptorchid preterm infants failed to show the normal rise in plasma testosterone in the first postnatal week. This rise is thought to relate to residual maternal human chorionic gonadotrophin in the neonatal circulation. Infants with cryptorchidism also failed to show the later testosterone surge in the second month which has been related to endogenous gonadotrophin release. We speculate that inadequate stimulation of testosterone release by human chorionic gonadotrophin in the fetus might contribute to the pathogenesis of cryptorchidism in preterm infants. Our findings have implications for the medical treatment or possible prophylaxis of undescended testes in premature babies. PMID- 2904245 TI - Plasma concentrations of gastrin and somatostatin after breast feeding in 4 day old infants. AB - The plasma concentrations of gastrin and somatostatin were measured by radioimmunoassay before and after breast feeding in healthy 4 day old infants who had been born at full term. The mean (SD) concentrations of gastrin and somatostatin before breast feeding were 120 (30) pmol/l and 35 (12) pmol/l, respectively. Breast feeding in these infants was not followed by increased concentrations of gastrin and somatostatin in peripheral blood. High preprandial peptide concentrations, as seen during the neonatal period may limit the further release of peptide after feeding. PMID- 2904246 TI - Reticulospinal neurons in lamprey: transmitters, synaptic interactions and their role during locomotion. PMID- 2904247 TI - [2 benzoylquinoxaline metabolites of chlordiazepoxide (Librium)]. PMID- 2904248 TI - Prescribing of psychotropic medication by primary care physicians and psychiatrists. AB - This study investigates the prescribing of psychotropic medications by primary care physicians and psychiatrists using the National Ambulatory Medical Care Survey database. Results indicate that primary care practitioners provide a larger percentage of psychotropic drug visits than psychiatrists in every psychotropic class except for those patients prescribed lithium. In addition, the two provider groups differed in the relative proportions of the classes of psychotropic drugs prescribed. Primary care physicians prescribed anxiolytics most frequently, while psychiatrists prescribed antidepressants most often. Finally, in all therapeutic classes, when a psychotropic medication was prescribed, psychiatrists typically provided a mental health diagnosis, while primary care physicians did not. PMID- 2904249 TI - Ferrihaemoglobin formation by amyl nitrite and sodium nitrite in different species in vivo and in vitro. AB - The ferrihaemoglobin (HbFe3+) formation by amyl nitrite (AN) or sodium nitrite (NaNO2) was studied in different species including man, in vivo and in vitro. In in vivo studies AN was administered intravenously (i.v.), intramuscularly (i.m.), by inhalation, or orally. NaNO2 was injected i.v.. AN i.v. produced HbFe3+ much more rapidly than NaNO2 in dogs, cats, rabbits, and rats. In dogs, i.m. injection of AN was followed by a very slow linear increase in the HbFe3+ content. Inhalation of AN did not lead to HbFe3+ formation in dogs unless it was rebreathed in a closed (bag) or not completely open (gas mask) system. HbFe3+ was produced by oral AN in dogs, the effect being enhanced by addition of DMSO. Inhalation of AN by human volunteers in a gas mask and from ampoules crushed close to the nose did not induce haemoglobin oxidation to a practically significant extent, but it was associated with headache, tiredness, dizziness, and a fall in blood pressure. In in vitro studies, in contrast to NaNO2, AN produced HbFe3+ instantaneously in erythrocytes of various species and in purified human haemoglobin. AN 1 mol yielded 2 mol Fe3+. Only 20% of the oxygen released during the oxidation of haemoglobin by AN or NaNO2 was recovered. In 0.2 M phosphate buffer, pH 7.4, 0.01 mol O2/mol AN was consumed. CO2 was released in the presence of AN, but not of NaNO2, from blood, plasma, and 0.02 M NaHCO3 solution. The ratio (lactate)/(pyruvate) decreased when HbFe3+ was formed by AN or NaNO2. PMID- 2904250 TI - Effects of amyl nitrite on circulation, respiration and blood homoeostasis in cyanide poisoning. AB - The effects of intravenously (i.v.) administered or inhaled amyl nitrite (AN) were followed under chloralose anaesthesia in intact and cyanide-poisoned, spontaneously breathing beagles. The i.v. doses of AN were 0.03 and 0.15 mmol/kg and the i.v. dose of KCN was 0.06 mmol/kg. AN was inhaled in a closed system at 0.15 mmol/kg without previous poisoning and, in addition, at 0.074 mmol/kg (two ampoules at 0.3 ml AN) during artificial ventilation after poisoning with 0.045 mmol KCN/kg i.v.. Mean arterial pressure decreased by 15 and 40 mmHg, respectively, after i.v. injection of AN, associated with bradycardia and lowered peripheral blood flow. Respiratory minute volume rose by 65% with the higher dose. Arterial pO2 decreased by 20 mmHg while pCO2 rose by 6 mmHg. Within 30 min of injection, these changes were only partially reversible. Similar results were obtained following inhalation of AN in a closed system. Lactic acidosis and lowering of pH were produced by the i.v. route, but not by inhalation. Total haemoglobin increased. The lethality of KCN was abolished with AN doses that produced 10-30% ferrihaemoglobin. Artificial ventilation and simultaneous inhalation of AN after poisoning with lethal doses of KCN turned out to be ineffective therapeutic measures. The findings are compared with those of other papers dealing with cyanide poisoning and AN. It is pointed out that, for the present, there is no experimental proof for another antidotal mechanism of action of AN than ferrihaemoglobin formation. PMID- 2904251 TI - Identification of phenothiazine antihistamines and their metabolites in urine. AB - Identification of the phenothiazine antihistamines alimemazine, dimetotiazine, isothipendyl, mequitazine, oxomemazine, promethazine, thiethylperazine, triflupromazine and their metabolites in urine is described. After acid hydrolysis of the conjugates, extraction and acetylation the urine samples were analysed by computerized gas chromatography-mass spectrometry. Using ion chromatography with the selective ions m/z 58, 72, 100, 114, 124, 128, 141, and 199 the possible presence of phenothiazine antihistamines and/or their metabolites was indicated. The identity of positive signals in the reconstructed ion chromatograms was confirmed by a visual or computerized comparison of the stored full mass spectra with the reference spectra. The ion chromatograms, reference mass spectra and gas chromatographic retention indices (OV-101) are documented. The procedure presented is integrated in a general screening procedure (general unknown analysis) for several groups of drugs. PMID- 2904252 TI - Virus-specific proteins and RNAs from cells infected with hemorrhagic fever with renal syndrome (HFRS) viruses derived from endemic areas of the U.S.S.R. AB - Cell-associated proteins of rodent (CG-1820 strain) and human (K-27 and 360 strains) hantaviruses isolated in the European endemic areas of the U.S.S.R. are antigenically similar as revealed by immunoprecipitation and immunoblotting assays. Nucleocapsid-associated RNAs of representative hantaviruses of four antigenic groups [Sugiyama et al. (1987) J Gen Virol 68: 979-987] have unique PAGE patterns. "Electropherotyping" of the RNAs isolated from infected cells might be used for identifying and distinguishing hantaviruses. PMID- 2904253 TI - Entry of human immunodeficiency virus (HIV) into MT-2, human T cell leukemia virus carrier cell line. AB - The ultrastructural features of early events in human immunodeficiency virus (HIV) infection of HTLV-I-carrying MT-2 lymphocytes were investigated by electron microscopy. Within 10 min after virus inoculation at 37 degrees C, the virus entered the cell in two ways; (1) the virus attached to the lymphocyte membrane and the viral core entered the cell after fusion of the viral envelope with the cell membrane, and (2) part of the cell membrane to which the virus was attached became invaginated, the virus became trapped in a phagosome and the viral core entered after the fusion of viral membrane with the vacuolar membrane. Thereafter, some cells were observed to form syncytia with multiple nuclei. When the proportion of anti-HIV antibody-reactive cells present exceeded 90%, virus production was strongly activated, and budding on the cell membrane was frequently observed. PMID- 2904254 TI - Comparison by restriction fragment pattern analysis and molecular characterization of some European isolates of Suid herpesvirus 1: a contribution to strain differentiation of European isolates. AB - Eleven European isolates of Suid herpesvirus type 1 (SHV-1) were compared by restriction fragment pattern analyses and Southern blot hybridization using different genomic probes. The presence of strain discriminative 4 major genome types and several subtypes as well as the molecular distinctions between these were demonstrated. Evolutionary relationships between the different types are suggested on the basis of homologous restriction fragment length polymorphisms. PMID- 2904255 TI - Pvu II polymorphism of low density lipoprotein receptor gene and familial hypercholesterolemia. Study of Italians. AB - Familial hypercholesterolemia is a metabolic disorder inherited as an autosomal dominant trait characterized by an increased plasma low density lipoprotein (LDL) level. It has been demonstrated that the disease is caused by several different mutations in the LDL receptor gene. Although early identification of individuals carrying the defective gene could be useful in reducing the risk of atherosclerosis and myocardial infarction, the available techniques for determining the number of the functional LDL receptor molecules are not sufficiently accurate. The recent isolation of the LDL receptor gene now makes it possible to use restriction fragment length polymorphisms to study the inheritance of the defective allele in families with familial hypercholesterolemia. In the present study, we report the use of a Pvu II restriction fragment length polymorphism to follow the inheritance of familial hypercholesterolemia in a total of 79 patients from 37 different families. This restriction fragment length polymorphism allowed unequivocal diagnosis in 32.5% of the cases. Furthermore, in the Italians studied, the absence of a polymorphic Pvu II cutting site (P1 allele) was found to be strongly associated with familial hypercholesterolemia. PMID- 2904256 TI - Infectivity and virulence of Australian strains of Moraxella bovis for the murine and bovine eye in relation to pilus serogroup sub-unit size and degree of piliation. AB - The degree of piliation of 29 haemolytic and 4 non-haemolytic Australian strains of Moraxella bovis representing 7 different pilus antigen groups was determined. The infectivity and virulence for the eye was measured in steroid-treated mice and in cattle. Non-piliated strains failed to infect the murine eye. Most moderately or heavily piliated strains reproducibly produced the highest infectivity and virulence scores in mice when compared with lightly or very lightly piliated strains (p less than 0.05). Non-haemolytic, piliated strains were infective and in one instance virulent for mice. Almost similar levels of infectivity and virulence were observed for 7 representative haemolytic strains tested in both cattle and mice. The relative molecular weight of pilin sub-units was compared using sodium dodecyl-sulphate polyacrylamide gel electrophoresis. Three classes of pili, alpha, beta and gamma of ascending sub-unit size were identified among the 7 pilus antigen serogroups. Pilin sub-unit size bore no relationship to the degree of piliation but most strains that were highly virulent in mice and cattle expressed alpha and gamma sub-units. Some strains appeared capable of switching from alpha to beta or form beta to gamma sub-unit production. PMID- 2904257 TI - Vaccination against infectious bovine keratoconjunctivitis: protective efficacy and antibody response induced by pili of homologous and heterologous strains of Moraxella bovis. AB - The protective effect of 2 Moraxella bovis pili vaccines against infectious bovine keratoconjunctivitis (IBK) experimentally induced by homologous or heterologous strain challenge with virulent, haemolytic M. bovis strain, Dal 2d, was measured in trials using weaned calves aged 3 to 7 months. Purified pili vaccines were prepared from haemolytic strain Dal 2d, (pilus serogroup IV), and haemolytic strain Epp 63, (pilus serogroup III). Calves were challenged by conjunctival instillation of 1 x 10(9) colony forming units of virulent M. bovis strain Dal 2d 14 days after the second of 2 subcutaneous doses of vaccine. Each consisted of 200 micrograms of pili in alum-oil adjuvant administered at an interval of 21 days. In trial 1 the level of protection against challenge with the homologous strain was 46.7% (p less than 0.01). Small, rapidly resolving lesions of IBK occurred in some vaccinates compared with a larger proportion of severe lesions that required treatment in non-vaccinated calves (p less than 0.025). In trial 2, the level of protection against IBK after exposure of vaccinates to the homologous Dal 2d strain was 72.7%, but no significant level of protection or reduction in the size and duration of lesions was apparent in similarly challenged calves vaccinated with Epp 63 pili when contrasted with susceptible, non-vaccinated controls. No marked reduction in the duration of infection with M. bovis Dal 2d following challenge resulted from vaccination with pili of either of the serogroups III or IV. Rising homologous serum IgG antibody titres to serogroups III and IV pili were recorded in response to vaccination with each antigen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2904258 TI - Enterotoxaemia in a foal due to Clostridium perfringens type A. PMID- 2904259 TI - Molecular characterization of the solubilized receptor of somatostatin from rat pancreatic acinar membranes. AB - The somatostatin receptors on rat pancreatic acinar membranes were demonstrated by use of a radioiodinated (125I-) analogue of somatostatin (SMS 204-090 or [Tyr3]SMS). The tracer was found to bind to the receptor with a Kd of 58 pM. The number of sites detected by this tracer (4.7 pmol/mg of protein) was 5-10 times higher than the number of sites previously found with other tracers. Since the level of non-specific binding was also very low as compared with findings with other tracers, 125I-204-090 might be of interest in future attempts to characterize the somatostatin receptors in the pancreas. The prelabelled membranes were solubilized with 1% CHAPS, and the solubilized complexes were found to adsorb to wheat-germ-agglutinin-coupled agarose, from which they could be eluted with 4 mM-triacetylchitotriose. The complexes within this eluate were shown by gel filtration on Trisacryl GF-2000 to have an Mr of about 400,000. The dissociation of the complexes was augmented both within the membranes as well as in the solubilized state by incubation with the GTP analogue guanosine 5'-[gamma thio]triphosphate, indicating that the complexes are probably functionally linked to a guanine-nucleotide-binding regulatory protein. After SDS/slab-gel electrophoresis and autoradiography of cross-linked complexes after treatment with the heterobifunctional reagent N-5-azido-2-nitrobenzoyloxysuccinimide, a broad band occurred at approximately Mr 90,000 both in the membranes and in the eluates of complexes after lectin-adsorption chromatography. We conclude that the augmentation of the number of detectable sites for binding of somatostatin, as well as the very low level of non-specific binding obtained by the use of 125I [Tyr3]SMS as tracer, has made it possible for us to demonstrate the solubilization of the somatostatin receptor in conjunction with its ligand and a GTP-binding regulatory protein, and we have succeeded in cross-linking 125I [Tyr3]SMS to a binding subunit of Mr 90,000 in the membranes and in demonstrating the presence of the same labelled binding subunit within complexes solubilized and chromatographed on a lectin column before cross-linking. PMID- 2904260 TI - Purification and characterization of CS2, a sialic acid-specific haemagglutinin of enterotoxigenic Escherichia coli. AB - CS2 fimbriae of enterotoxigenic Escherichia coli were purified and characterized. The surface haemagglutinins (fimbriae) were detached by sonication from a strain producing only the CS2 fimbriae. Isolation was carried out by gel filtration on a Sepharose 4B column. After depolymerization, the fimbriae subunits were purified on a Sephacryl S-300 column in 8.0 M-guanidinium chloride. From 1 litre of medium, 4-6 mg of purified fimbriae was obtained. We found that CS2 fimbriae were completely dissociated by saturated guanidinium chloride into subunits with a molecular mass of 16.5 kDa. CS2 fimbriae was sialic acid-specific, since sialic acids were the most potent inhibitors, and neuraminidase treatment of erythrocytes abolished haemagglutination. Both fimbriae and fimbrial subunits were found to bind to bovine erythrocytes. The binding of subunits to erythrocytes could be inhibited with low concentrations of sialyl-lactose. PMID- 2904261 TI - The effect of ketone bodies on alanine and glutamine metabolism in isolated skeletal muscle from the fasted chick. AB - The effects of ketone bodies on the metabolism of alanine and glutamine were studied in isolated extensor digitorum communis (EDC) muscles from 24 h-fasted chicks. (1) Acetoacetate and DL-beta-hydroxybutyrate (4 mM) markedly inhibit branched-chain amino acid (BCAA) transamination and alanine formation. (2) Ketone bodies (1 and 4 mM) increase the intracellular concentration and release of glutamate and glutamine, suggesting that inhibition of BCAA transamination does not limit intracellular availability of glutamate for alanine synthesis. (3) Ketone bodies (1 and 4 mM) do not affect glucose uptake by muscles, but decrease the rate of glycolysis as well as the intracellular concentration and release of pyruvate in muscles. (4) Addition of 12 mM-glucose increases the formation of alanine in muscles incubated in the absence of ketone bodies, but has no effect in muscles incubated in the presence of 4 mM ketone bodies. (5) Addition of 5 mM pyruvate to the media prevents the inhibiting effect of ketone bodies on BCAA transamination and alanine synthesis. These results suggest that ketone bodies decrease alanine synthesis by limiting the intracellular availability of pyruvate, owing to inhibition of glycolysis, and inhibit BCAA transamination by decreasing the intracellular concentration of amino-group acceptors such as pyruvate in EDC muscles from fasted chicks. PMID- 2904263 TI - Modeling of the homoeo domain suggests similar structure to repressors. AB - The sequences of the homoeo domain containing the three alpha-helices were modeled based on secondary structure prediction, sequence homologies and coordinates of known helix-turn-helix motif containing DNA-binding proteins. The model reveals very similar three dimensional structure to repressors and suggest binding to DNA with its helix 3. PMID- 2904262 TI - Nucleotide sequence of the gene encoding the GMP reductase of Escherichia coli K12. AB - (1) The nucleotide sequence of a 1991 bp segment of DNA that expresses the GMP reductase (guaC) gene of Escherichia coli K12 was determined. (2) This gene comprises 1038 bp, 346 codons (including the initiation codon but excluding the termination codon), and it encodes a polypeptide of Mr 37,437 which is in good agreement with previous maxicell studies. (3) The sequence contains a putative promoter 102 bp upstream of the translational start codon, and this is immediately followed by a (G + C)-rich discriminator sequence suggesting that guaC expression may be under stringent control (4) The GMP reductase exhibits a high degree of sequence identity (34%) with IMP dehydrogenase (the guaB gene product) indicative of a close evolutionary relationship between the salvage pathway and the biosynthetic enzymes, GMP reductase and IMP dehydrogenase, respectively. (5) A single conserved cysteine residue, possibly involved in IMP binding to IMP dehydrogenase, was located within a region that possesses some of the features of a nucleotide binding site. (6) The IMP dehydrogenase polypeptide contains an internal segment of 123 amino acid residues that has no counterpart in GMP reductase and may represent an independent folding domain flanked by (alanine + glycine)-rich interdomain linkers. PMID- 2904264 TI - Centrilobular expression of ethanol-inducible cytochrome P-450 (IIE1) in rat liver. AB - Western blot analysis of digitonin eluates as well as immunohistochemical analysis revealed a 30-fold higher concentration of cytochrome P-450IIE1 in the centrilobular than in the periportal regions of the rat liver. Ethanol treatment caused a selective centrilobular induction of P-450IIE1, whereas phenobarbital induced P-450IIB1/2 in both liver lobule regions. The heterogeneous distribution pattern of P-450IIE1 was also observed in cells isolated from either region and correlated to the relative content of P-450IIE1 mRNA in the two cell types. The regiospecific expression and induction of P-450IIE1 may explain why several hepatotoxins, known to be metabolized by this isozyme, primarily damage the centrilobular region in the liver. PMID- 2904265 TI - Increased 3H-thymidine incorporation into DNA of organ-cultured adrenal explants from rats injected with corticotropin and/or cysteamine. AB - The effect of a single injection of cysteamine /CySH/ - a sulfhydryl substance, known to deplete tissue content of somatostatin /SS/ - on 3H-thymidine incorporation into DNA of rat adrenal explants incubated in vitro was investigated. It was shown that: 1/ Single in vivo injection of ACTH or of CySH increased 3H-thymidine incorporation into DNA of the organ-cultured adrenals, 2/ Dexamethasone reduced the 3H-thymidine uptake, but that decrease did not attain statistical significance versus controls. PMID- 2904266 TI - Selective inhibition of excitatory amino acid-stimulated phosphoinositide hydrolysis in the rat hippocampus by activation of protein kinase C. AB - The relative roles of protein kinase C in regulating excitatory amino acid-, cholinoceptor-, and adrenoceptor-stimulated phosphoinositide hydrolysis were studied. Slices of rat hippocampus were prelabeled with [3H]-myo-inositol, and agonist-induced [3H]-phosphoinositide hydrolysis was measured by the formation of [3H]-inositol monophosphate ([3H]-IP) in the presence of lithium ion. Activation of protein kinase C with phorbol 12,13-dibutyrate (PDB) (10(-6) M) completely inhibited ibotenate (IBO) (10(-3) M)-induced [3H]-phosphoinositide hydrolysis. Half-maximal inhibition was observed at about 10(-7) M PDB. Higher concentrations of PDB were required to inhibit stimulation of [3H]-IP by either carbachol (CARB) (10(-3) M) or norepinephrine (NE) (10(-4) M, and only partial inhibition could be attained. Preincubation with staurosporine (STAURO) (10(-5) M) or 1-(5 isoquinolinesulfonyl)-2-methylpiperazine (H-7) (10(-4) M), inhibitors of protein kinase C, potentiated IBO- but not CARB- or NE-induced stimulation of [3H]-IP. PDB inhibition of IBO- or NE-stimulated [3H]-phosphoinositide hydrolysis was reversed by co-addition of STAURO or H-7. In the case of IBO + STAURO, this reversal was to the potentiated level observed with STAURO alone. Enhanced agonist stimulation and reversal of PDB inhibition were also produced by STAURO when [3H]-phosphoinositide hydrolysis was stimulated by either L-glutamate or quisqualate. These experiments show that direct activation of protein kinase C by PDB leads to inhibition of phosphoinositide hydrolysis mediated by excitatory amino acid receptors, cholinoceptors, or adrenoceptors. However, the enhanced agonist-stimulated phosphoinositide hydrolysis elicited by inhibitors of protein kinase C suggests that, when protein kinase C is indirectly activated, only excitatory amino acids rapidly inhibit further receptor-coupling. PMID- 2904267 TI - Structure of T cell antigen receptor beta chain in synovial fluid cells from patients with rheumatoid arthritis. AB - We attempted to identify a clonal proliferation of T cells from synovial fluid samples from patients with rheumatoid arthritis, using techniques of restriction fragment length polymorphism. We used probes for the beta chain of the T cell receptor to analyze restriction fragments prepared from the genomic DNA of synovial fluid mononuclear cells from 10 patients and synovial fluid T cell preparations from 5 additional patients. The results demonstrated unarranged (germline) T cell receptor gene fragments of DNA in all cell preparations, indicating the lack of clonality of rheumatoid arthritis synovial fluid T cells. PMID- 2904268 TI - New approach in bioavailability study of two formulations of ethyl loflazepate. AB - The disposition of ethyl loflazepate (Victan) was studied on 12 healthy male volunteers after administration of the two oral formulations of the drug: one 4 mg tablet and two 2-mg tablets according to an open crossover single dose comparison. A model-independent analysis and a model-dependent approach were used to treat experimental data. Appropriate statistical tests (ANOVA, Wilcoxon test, Westlake test for model-independent parameters; principal components analysis, Hotelling T2 test for model-dependent parameters) demonstrated the bioequivalence of the two formulations. PMID- 2904269 TI - Special pharmacology of the new sulfonylurea glimepiride. AB - Glimepiride (Hoe 490) is a new sulfonylurea. After oral administration of Hoe 490 to rabbits, blood glucose was lowered 3.5 times more than after glibenclamide (HB 419) and after intravenous administration, 2.5 times more. This superiority in efficacy was demonstrated by onset, maximum and duration of action. In rats, intravenous and oral Hoe 490 has a much shorter effect on blood glucose than HB 419, but the initial effect of Hoe 490 orally was up to 6 times and i.v. up to 2 times stronger than that of HB 419. In dogs, oral and intravenous Hoe 490 had a considerably longer blood glucose-lowering effect than HB 419. However, the effect of intravenous Hoe 490 was only half as intense as that of HB 419 in the first hours after treatment and the effect of oral Hoe 490 was initially stronger and thereafter temporarily distinctly weaker than that of HB 419. The more rapid decrease in blood glucose in the dog after oral administration of Hoe 490 was accompanied by a correspondingly earlier and higher plasma insulin increase. In accordance with the less intense initial blood glucose decrease in the dog after intravenous Hoe 490 there was a weaker and slower rise and faster drop of plasma insulin. The long action of oral and intravenous Hoe 490 in the dog can, however, not be sufficiently explained by the plasma insulin values. In the isolated rat pancreas perfused with glucose-free medium, HB 419 released glucagon beside insulin and somatostatin. The threshold concentration for the glucagon secretion was lower as those for the insulin and somatostatin release.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2904270 TI - Clinical pharmacokinetics of ibopamine on different diseases and conditions. AB - The pharmacokinetics of ibopamine was studied after single dose and after single and multiple dosing. The studies after single dose were conducted in normal subjects (NS) and in patients with congestive heart failure (CHF) of NYHA functional classes II, III and IV, in patients with chronic renal impairment (CRI), with hepatic cirrhosis (HC) and in elderly patients. Furthermore, ibopamine-quinidine pharmacokinetic interaction and the effects of food on plasma kinetics were evaluated in NS. The studies after single and multiple dosing were conducted in CHF patients. The effects were also studied of chronic oral ibopamine treatment on the pharmacokinetics of digoxin after chronic oral dosing and of treatment with digoxin on ibopamine pharmacokinetics. Ibopamine appears to be rapidly and extensively absorbed, quickly hydrolyzed to epinine and then excreted mainly through the kidneys either after being sulpho-conjugated or oxidized to homovanillic acid and 3,4-dihydroxyphenylacetic acid. Epinine is thought to be the therapeutically active moiety of the drug. In patients with CHF epinine pharmacokinetics does not depend on the NYHA functional class, and it falls within the same area as that in NS; the pharmacokinetics of epinine does not vary during the repeated administration of the drug for one month. In patients with CHF the pharmacokinetic data do not suggest the need to adjust the dose according to the NYHA functional class. In patients with CRI the pharmacokinetics of epinine does not vary with the degree of renal impairment. In HC patients AUC and Cmax of epinine seem to be higher than in NS; in these patients a higher amount of epinine is excreted into urine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2904271 TI - The catalepsy test: its ups and downs. AB - The typical catalepsy test consists of placing an animal into an unusual posture and recording the time taken to correct this posture. This time is regarded as an index of the intensity of catalepsy. Catalepsy is a robust behavior, and the lack of standardization does not usually hinder its actual detection. However, the intensity of the cataleptic effect is influenced by minor methodological differences, and thus interpretation and comparison of results across laboratories are difficult. The behavioral catalepsy test can use any of several different apparatus, including wire grids, parallel bars, platforms, or pegs, to situate the animals in unusual positions. The most common, however, is the "bar test," and despite its wide use in psychopharmacological research, even parameters of this test are not standardized. The present article reviews the wide variety of parameters chosen by investigators that measure catalepsy. The methodological issues of repeated testing, scaling of scores, apparatus, animal weight, maximal test duration, behavioral criteria, and other influences are discussed. In addition, a brief review of the neuropharmacological basis of catalepsy is also included. Finally, it is argued that a universal, standardized bar test be adopted by researchers. New data on a novel automated bar test in the Digiscan Activity Monitoring System is presented. PMID- 2904272 TI - Prophylaxis of whole season hay fever symptomatology: a comparison of terfenadine with chlorpheniramine. PMID- 2904273 TI - Angiographically-induced infection of the aorta. AB - We present three cases of infection of the native aorta following angiography. The infection was an incidental finding at operation in two patients, while a third presented with fulminant sepsis. All had debridement of the retroperitoneum and underwent successful extraanatomic bypass. We feel caution is warranted in placing a retroperitoneal graft even in suspected aortic sepsis. Prophylactic antibiotics may be advisable to protect against infection of atherosclerotic plaque during angiography. PMID- 2904274 TI - In vivo and in vitro expression of porcine D-amino acid oxidase: in vitro system for the synthesis of a functional enzyme. AB - In vivo expression of D-amino acid oxidase (EC 1.4.3.3, DAO), one of the principal and characteristic enzymes of the peroxisomes of porcine kidney, was examined by use of cloned complementary DNA [Fukui, K., Watanabe, F., Shibata, T., & Miyake, Y. (1987) Biochemistry 26, 3612-3618]. RNA blot hybridization analysis revealed that DAO is expressed abundantly in kidney and liver, is expressed significantly in brain, but is not expressed in lung of pig. Three mRNA species were expressed in kidney and liver, but only one was detected in brain. These results show the presence of tissue-specific regulation of DAO gene expression. In vitro expression of a functional enzyme was achieved through the construction of a recombinant plasmid containing an SP6 promoter and a restriction enzyme fragment of cDNA to generate a DAO-specific RNA transcript. The in vitro translation product of the capped RNA transcript showed significant catalytic activity, which was inhibited strongly by benzoate, a potent inhibitor of DAO. The kinetic properties of the in vitro synthesized enzyme were comparable to those of the purified enzyme from porcine kidney. It is now possible to synthesize a functional D-amino acid oxidase in vitro and to investigate its structure-function relationships. PMID- 2904275 TI - Effect of hydrostatic pressure on the mitochondrial ATP synthase. AB - The effects of hydrostatic pressure on three different preparations of mitochondrial H+-ATPase were investigated by studies of the hydrolytic activity, of the spectral shift and quantum yield of the intrinsic protein fluorescence, and of filtration chromatography. Both membrane-bound and detergent-solubilized forms of the mitochondrial F0-F1 complex were reversibly inactivated in the pressure range of 600-1800 bar, whereas with soluble F1-ATPase the inactivation was irreversible. Pressure inactivation of soluble F1-ATPase was facilitated by decreasing the protein concentration, indicating that dissociation is an important factor. In the presence of 30% glycerol, soluble F1-ATPase becomes inactivated by pressure in a reversible fashion, recovering the original activity. ATPase activity measured in an aqueous medium returns to the original values when incubated under high pressure in a glycerol-containing medium without substrate and is even enhanced when Mg-ATP is present. ATP hydrolysis returns to 80% of its original value in the case of the F0-F1 complex. Fluorescence studies under pressure revealed a red shift in the spectral distribution of the emission of tyrosine fluorescence of soluble F1-ATPase. A decrease in the quantum yield of intrinsic fluorescence was also observed upon subjection to pressure. The fluorescence intensity decreased monotonically as a function of pressure when the sample was in an aqueous medium, whereas it presented a biphasic behavior in a 30% glycerol medium. Gel filtration studies demonstrated that the hydrodynamic properties of the F1-ATPase are preserved if the enzyme is subjected to pressure in the presence of glycerol but they are modified when the same procedure is performed in an aqueous medium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2904276 TI - Biochemical and functional characterization of three types of coated vesicles in bovine adrenocortical cells: implication in the intracellular traffic. AB - Three populations of pure coated vesicles from adrenocortical cells, differing in their density, i.e., 1.125-1.155, 1.155-1.175, and 1.175-1.210 g/cm3, are obtained after separation on two successive sucrose-2H2O gradients. They are involved in LDL internalization and in the receptor cycle as confirmed by the presence, in each population, of the LDL receptor. Electron micrographs confirm the existence of three homogeneous populations exhibiting the typical polygonal structure of the clathrin coat. They differ in their size distribution (small, congruent to 70-nm diameter; medium, congruent to 90-nm diameter; large, congruent to 110-nm diameter) and in the organization of clathrin and of the coat proteins as evidenced on electrophoreses carried out under nondenaturing and denaturing conditions. Activity measurements of marker enzymes, phosphodiesterase and galactosyltransferase, suggest that medium coated vesicles might originate from plasma membranes and small ones from the Golgi complex. Large coated vesicles exhibit phosphokinase enzyme and substrate polypeptides different from those of the two other populations, tubulins being the preferred kinase substrates for the small and medium coated vesicles. These kinases are autophosphorylating enzymes and are revealed, by nondenaturing electrophoreses, as different high molecular mass complexes in the three populations. Clathrin and coat proteins are not part of these complexes. PMID- 2904277 TI - Assessment of the number of nucleotide binding sites on chloroplast coupling factor 1 by the continuous variation method. AB - The method of continuous variation (Job plot analysis) and difference absorbance spectroscopy were used to investigate the binding of 2'(3')-(trinitrophenyl)-ADP and -ATP to chloroplast coupling factor 1 (CF1). Experiments performed at a low total concentration (30 microM) of nucleotide and enzyme binding sites (assuming three or four binding sites per CF1) could be interpreted in terms of approximately three nucleotide binding sites per CF1. At higher total concentrations (100 and 400 microM), the number of apparent binding sites increased to almost four. Computer-generated Job plots, using a protein-ligand complex formation scheme of n independent, nonequivalent binding sites, gave good fits to the experimental data at all concentrations when four binding sites were modeled. The dissociation constant of the fourth site was estimated to be approximately 20 microM. Additional nucleotide binding sites were not directly observed by this method and, if they exist, have very weak binding affinities (dissociation constants greater than approximately 1 mM). PMID- 2904278 TI - Substrate specificity of mammalian folylpoly-gamma-glutamate synthetase for 5,8 dideazafolates and 5,8-dideaza analogues of aminopterin. AB - The substrate specificity of pig liver folylpolyglutamate synthetase (tetrahydrofolate:L-glutamate gamma-ligase (ADP-forming), EC 6.3.2.17) for classical 5,8-dideaza analogues of folic acid, isofolic acid aminopterin and isoaminopterin has been investigated. 5,8-Dideazafolate and 5,8 dideazaaminopterin are very effective substrates with activities approaching those of the best reduced folate substrates. The analogous isofolate analogues are less effective substrates, but still better than folic acid. The 5-chloro substituent is the only modification that consistently increases the on rate, with 5-chloro-5,8-dideazaaminopterin being the most effective substrate found, thus far, for the enzyme. Methylation at positions 9 or 10 generally decreases binding, while 5-methylation increases the binding of 4-oxoquinazolines, but decreases the binding of their 4-amino counterparts. The presence of a formyl group at N9 or N10 has the opposite effect, decreasing the binding of 4-oxo analogues while increasing the rate for 4-amino derivatives. Increases in on rate with methyl, formyl or 4-amino substitutions are only significant when the parent compound is a poor substrate, suggesting that these groups do not interact directly with the enzyme but cause conformational changes in the structure of the substrate that influence binding to the enzyme. PMID- 2904279 TI - Lack of D-amino-acid oxidase activity causes a specific renal aminoaciduria in the mouse. AB - Thin-layer chromatography and amino acid analysis showed that urine of mutant ddY/DAO- mice lacking D-amino-acid oxidase activity contained more serine, proline, alanine and methionine than that of normal ddY/DAO+ mice. Among these four, an increase in alanine was conspicuous. However, the urinary levels of 11 other amino acids and glucose were not different between the ddY/DAO- and ddY/DAO+ mice. Amino acid analysis showed that the plasma levels of serine, proline and methionine were not elevated in the ddY/DAO- mice, though a slight increase in alanine was observed. Genetic crosses showed that aminoaciduria and lack of D-amino-acid oxidase activity were concomitantly transmitted as a set through generations. These results indicated that the lack of enzyme activity caused a specific renal aminoaciduria. Whether this enzyme merely diminishes the D-amino acid load presented for reabsorption, or actually participates catalytically in the reabsorption process, remains undetermined. PMID- 2904280 TI - Dimorphism-associated changes in intracellular pH of Candida albicans. AB - Intracellular pH (pHi) was monitored during pH-regulated dimorphism of Candida albicans using two different methods: (1) by steady-state distribution of propionic acid and (2) by use of polyene antibiotic, nystatin. There was no significant change in pHi during the first 120 min in either bud- or germ tube forming populations. However, there was a rapid increase around 135 min which also coincided with the time of evagination. The magnitude of increase in pHi was different in the two populations; being 0.44 and 0.14 pH units in bud- and germ tube-forming populations, respectively. In the two diverging populations, the transient increase in pHi was followed by a rapid drop. The sharp rise in pHi of the population destined to form buds was sensitive to orthovanadate and to the depletion of K+ from the medium while this was not the case with germ tube forming cells. The results suggest that pHi may play an important role in the phenotypic divergence of C. albicans. PMID- 2904281 TI - [The action of sodium and potassium ions on the H+-ATPase activity of Escherichia coli K12 (lambda) membranes]. AB - The dependence of activity of H+-ATPase membranes of Escherichia coli K12 (lambda) grown anaerobically of potassium and sodium ions has been studied. The addition of K+ or Na+ to the reaction mixture causes an increase of H+-ATPase activity. The effect depended on conditions and keeping time of the preparation of membranes. The sensitivity of enzyme to potassium and sodium decreased with the rise of temperature from -20 degrees C to -4 degrees C and an increase of keeping time. PMID- 2904283 TI - Disruption of spermatogenesis is associated with decreased concentration of immunoreactive arginine vasopressin in testicular fluid. AB - We have previously shown that testicular fluid contains factors that can inhibit luteinizing hormone (LH)-stimulated androgen production by Leydig cells, and others have reported the presence of immunoreactive vasopressin (iAVP) in the testes as well as in vitro inhibition by vasopressin of Leydig cell-androgen production. In the current report, we have used an established radioimmunoassay (RIA) to measure the concentration of iAVP in testicular fluid and have related changes in iAVP concentration to disruption of the seminiferous tubules. Spermatogenesis was disrupted in adult rats by surgically establishing bilateral cryptorchidism. The concentration of iAVP decreased progressively from 349 +/- 52 to 61 +/- 5 pg/ml during 4 wk. When cryptorchidism was unilaterally established, the concentration of iAVP in fluid from that testis decreased to 116 +/- 19 pg/ml while the concentration of iAVP in the contralateral scrotal testis remained unaffected. Unilateral ligation of the ductuli efferentes also caused an equivalent unilateral decrease in iAVP to 110 +/- 15 pg/ml. The osmotic pressure of the testicular fluid was not altered by disruption of gametogenesis, and the extracellular "albumin space" was not increased. Therefore, the decrease in concentration of iAVP was probably not due to dilution with increased amounts of interstitial fluid. We conclude that the disruption of spermatogenesis is associated with a decrease in the concentration of iAVP in testicular fluid and suggest that AVP or a similar peptide may be involved in the intratesticular mechanisms associated with increased production of androgen by Leydig cells after disruption of spermatogenesis. PMID- 2904282 TI - Differences in aromatase activity between Leydig cells from the scrotal and abdominal testis in the naturally unilateral-cryptorchid boar. AB - In an earlier study, estrogen production was much lower in Leydig cells from the abdominal than from the scrotal testis in naturally occurring unilateral cryptorchidism in the boar. A more direct assessment of aromatase activity was made in thirty-two mature male pigs to examine this observation further, using nonradioactive androstenedione (delta 4A 1.0 x 10(-6) M - 1.5 x 10(-5) M) and [1 beta, 2 beta-3H] delta 4A as substrates. Purified Leydig cells were prepared from normal boars and from unilaterally and bilaterally cryptorchid animals. Combined estrone sulfate (E1S) and estrone (E1) formation from delta 4A were measured by radioimmunoassay. Little or no estrogen secretion was seen with cells from the abdominal testis in unilaterally cryptorchid boars (n = 7), and E1S formation from delta 4A was 6- to 14-fold higher for scrotal cells (n = 6). Aromatase activity as reflected in percent conversion of substrate to [3H]-labeled water was clearly lower in cells from the abdominal testis (1.10 +/- 0.08 and 11.22 +/- 0.7%, respectively, p less than 0.01, n = 6). No marked reduction was noted for unilaterally cryptorchid boars with an inguinally located testis (10.18 +/- 0.27 and 13.09 +/- 0.58% for inguinal and scrotal testes, respectively, n = 3). Concentrations of E1S in testicular arterial and venous blood (n = 9) gave additional evidence of lower estrogen production by the undescended testis of the cryptorchid boar. It was concluded that lower aromatase activity is present in Leydig cells of the abdominal testis. PMID- 2904284 TI - Receptor-mediated activation of detergent-solubilized guanylate cyclase. AB - Here for the first time we report the successful detergent-solubilization of the speract (Gly-Phe-Asp-Leu-Asn-Gly-Gly-Gly-Val-Gly) receptor and the subsequent activation of guanylate cyclase in response to receptor occupation. Sea urchin sperm membranes treated with a solution containing 0.5% LubrolR PX and 0.5% EmulphogeneR in the presence of MgCl2 and NaF released both the speract receptor and guanylate cyclase activity into solution. The solubilized apparent receptor was not sedimented at 400,000 x g x 15 min and was not retained by glass microfiber filters. In the presence of 125I-GGG(Y2)speract and dissuccinimidyl suberate, a major radioactive band at about Mr = 77,000 and minor bands at Mr = 35,000 and 150,000 were cross-linked. Speract but not resact (Cys-Val-Thr-Gly-Ala Pro-Gly-Cys-Val-Gly-Gly-Gly-Arg-LeuNH2) competed in the cross-linking reaction. The amount of 125I-GGG(Y2)speract bound to solubilized receptor did not increase in a linear manner as a function of added protein but instead was concave upward. The addition of speract but not resact to the solubilized preparation resulted in the activation of the enzyme guanylate cyclase; the extent of stimulation was dependent on the amount of enzyme protein added and also was concave upward. Approximately 900 nM speract half-maximally activated guanylate cyclase. These data suggest that the speract receptor and guanylate cyclase are closely apposed, even in detergent, or that they are the same molecule. PMID- 2904285 TI - [Effect of tranquilizers of the 1,4-benzodiazepine series on the xanthine oxidase activity of the rat brain]. AB - Experiments in vivo and in vitro on 90 rats were made to study the influence of 1,4-benzodiazepine tranquilizers (phenazepam, nitrazepam and diazepam) on cerebral xanthine oxidase activity. Phenazepam, nitrazepam and diazepam in the dose of 5 mg per 200 g bw were shown to reduce xanthine oxidase activity by 80.4%, 64.3% and 55.8%, respectively 2 h after intraperitoneal injection. 6 h after the injection of benzodiazepines the enzyme activity grows, but control values are achieved only after nitrazepam injection. In vitro experiments revealed direct influence of the tranquilizers on xanthine oxidase. Phenazepam inhibits xanthine oxidase activity in concentration as long as 10(-10) M (to 36.6%), and practically completely in 10(-6) M concentration. Nitrazepam and diazepam inhibit xanthine oxidase activity within concentration range between 10( 8) M (to 51.5% and 33.2%, respectively), and 10(-4) M (practically completely). The inhibition of xanthine oxidase activity is shown to be caused by the competition between hypoxanthine, the reaction substrate, and tranquilizer, to bind with the active site of the enzyme. PMID- 2904286 TI - [Monoclonal antibodies to alpha-endorphin effective in immunohistochemistry and immunoblotting]. AB - Four mouse monoclonal antibodies (E11, A8, F8, H5) to alpha-endorphin have been produced. The antibodies bind 12.5, 20.6, 9.6, 6.6% of 125I-beta-endorphin and 35.5, 15.1, 12.8, 12.2% of 125I-gamma-endorphin; the binding of 125I-alpha endorphin being taken for 100%. The binding of antibodies E11, A8, F8 and H5 to 125I-alpha-endorphin was 50% inhibited by unlabeled ligand in concentrations 5, 50, 30 and 35 nM respectively. Using tissue sections of rat pituitary it was shown that antibody E11 can be used for the localization of endorphin producing cells by immunofluorescence. The antibodies F8 and H5 effectively detected endorphin precursor proopiomelanocortin by immunoblotting. PMID- 2904287 TI - [The action of hypothalamic hormone on athymic mice with transplantable strains of human tumors]. AB - The sensitivity of human melanoma and lung cancer strains transplanted to nude mice to the synthetic hormone of hypothalamus--melanostatin has been defined. Correlation has been noted between the rate of melanoma growth inhibition, decrease in the rate of Na-fluorescent accumulation in the tumor and the tendency towards depression of the activity of energetic metabolism enzymes (SDH and alpha GPDH) in the treated tumors as compared to control. Moderate lymphopenia and absence of effect on the same enzymes of the lymphocytes was also observed. Fluorescent probes can be used in the estimation of the drug action on the tumor and organs. PMID- 2904288 TI - [Postradiation death and recovery of duodenal APUD cells in rats]. AB - Electron microscopy has revealed death of some of the apudocytes and recovery of the other ones in small intestine of rats after single total body irradiation in sublethal dose (5 Gy) and local fractionated irradiation (35 Gy, 7 Gy X 5) of the abdomen. The ability of EC-cells to form the autophagosomes was found. An absence of uniform reaction of different types of apudocytes to radiation is discussed. PMID- 2904289 TI - Hereditary X-linked thrombocytopenia maps to the same chromosomal region as the Wiskott-Aldrich syndrome. AB - Hereditary X-linked thrombocytopenia occurs either as isolated thrombocytopenia or as a part of the Wiskott-Aldrich syndrome (WAS). We studied X-linked thrombocytopenia in a family with eight affected male members, none of whom exhibited the increased susceptibility to infection that occurs in WAS. We found a significant linkage between thrombocytopenia and DXS 146, a marker on the proximal part of the short arm of the X-chromosome. WAS has previously been mapped to the same chromosomal region. The present findings indicate that X linked thrombocytopenia and WAS are closely related and may even be caused by different mutations of the same gene. This view is supported by our findings of atopic symptoms and minor deviations in immunologic variables among some of the affected subjects. PMID- 2904290 TI - The effect of cyclosporine A on infection of susceptible cells by human immunodeficiency virus type 1. AB - The effect of cyclosporine A (CyA) on the ability of the human immunodeficiency virus type 1 (HIV-1) to infect the H-9 T-cell leukemic line, as well as interleukin-2 (IL-2)-grown human peripheral blood-derived lymphocytes, has been studied. Pretreatment of H-9 cells and human lymphocytes with CyA over 24 hours completely prevented viral infection over a 21-day period, whereas the addition of drug at two hours postinfection with HIV-1 had a significant inhibitory effect on viral replication and expression of the virus-specific antigens p17 and p24. However, if CyA was added at later times to these lymphocytic cells, this inhibitory effect was lost. Indeed, the removal of CyA from cultures that had been treated from two hours after infection led to the rapid production of progeny virus. HIV-1 was able to infect peripheral blood lymphocytes obtained from each of four kidney allograft recipients on long-term CyA antirejection therapy, as long as drug was not included in the culture medium. In addition, we asked what effect pretreatment with CyA of cells of the U-937 monocytic line and primary cultures of human monocytes/macrophages might have on infection by HIV-1. CyA had no demonstrable effect on the ability of HIV-1 to infect cells of either type. PMID- 2904291 TI - Polyclonal reconstitution of human marrow after allogeneic bone marrow transplantation. AB - Clonal dominance suggestive of reconstitution of marrow from small numbers of pluripotent hematopoietic stem cells has been noted in different experimental and clinical situations. Recipients of human allogeneic marrow transplants have not been previously studied to determine if clonal dominance occurs in this clinical setting. Clonal analysis of 20 allogeneic marrow transplant recipients was performed on DNA from peripheral blood neutrophils using restriction fragment length polymorphisms on the X chromosome. Similar studies were performed on 16 of the donors. To analyze the results further, recipients were paired with their respective donors. There was no evidence of shifts in cell populations contributing to the X chromosome inactivation patterns in recipient marrow grafts when compared with their respective donors. A mathematical model based on binomial statistics was adapted to estimate the numbers of reconstituting pluripotent hematopoietic stem cells. There was no evidence of clonal dominance suggestive of oligoclonal reconstitution in marrow grafts after allogeneic marrow transplantation. This does not preclude the possibility of oligoclonal reconstitution in other marrow transplant settings such as autologous transplantation. PMID- 2904292 TI - Hypomethylation of ornithine decarboxylase gene and erb-A1 oncogene in human chronic lymphatic leukemia. AB - The methylation state of CCGG sites in and around the human ornithine decarboxylase gene, oncogenes c-myc and erb-A1, and actin genes were determined in human malignant leucocytes from patients with acute and chronic myeloid leukemia, chronic lymphatic leukemia, polycythemia vera, and multiple myeloma by means of isoschizomeric restriction endonuclease analysis. When compared with DNA from leucocytes of healthy controls, the ornithine decarboxylase and erb-A1 genes were substantially hypomethylated in all samples obtained from patients with chronic lymphatic leukemia. Hypomethylation of genes, particularly growth-related sequences, might be a crucial fact in the malignant transformation of human leucocytes. Its relatively simple detection from blood samples may prove clinically applicable in monitoring patients with chronic lymphatic leukemia. PMID- 2904293 TI - Role of the ventromedial hypothalamus in the regulation of adenohypophyseal immunoreactive dynorphin in the rat. AB - In this study, we have examined the role of the dorsomedial (DMH), ventromedial (VMH) and arcuate (ARH) nuclei of the hypothalamus in the control of hypothalamic and pituitary immunoreactive (ir) dynorphin (Dyn) A and ir-Dyn B in the rat, by evaluating the effect of discrete, bilateral radiofrequency lesions in these structures. Lesions limited to the VMH reduced the content of ir-Dyn in the anterior pituitary but not in the neurointermediate lobe or in the hypothalamus. Gel chromatographic analysis of anterior pituitary extracts confirmed that ir-Dyn is mainly associated with high molecular weight forms containing Dyn A and Dyn B in their sequence. Anterior pituitary extracts of VMH-lesioned rats displayed a clearly lower proportion of these forms. Destruction of the DMH affected only the hypothalamic content of ir-Dyn; ablation of the ARH did not cause any significant change. Our results suggest that ablation of the VMH may disrupt critical neuronal connections to the median eminence originating in this nucleus or crossing it and participating in control of the adenohypophyseal pool of ir-Dyn. PMID- 2904294 TI - APV, an N-methyl-D-aspartate receptor antagonist, blocks the hippocampal theta rhythm in behaving rats. AB - 2-Aminophosphonovaleric acid (APV), an N-methyl-D-aspartate (NMDA) receptor antagonist, was infused into the lateral ventricles of behaving rats. A 10 or 20 microgram dose of APV attenuated the hippocampal theta rhythm and the theta phase shift at the apical dendrites of hippocampal CA1 region. A selective suppression of the atropine-sensitive theta rhythm was suggested. PMID- 2904295 TI - [Long-term consumption of a diet with moderate medium chain triglyceride content does not inhibit the activity of enzymes involved in hepatic lipogenesis in the rat]. AB - The activities of glucose 6-phosphate dehydrogenase (EC 1.1.1.49), malic enzyme (EC 1.1.1.40), ATP-citrate lyase (EC 4.1.3.8), acetyl-CoA carboxylase (EC 6.4.1.2) and fatty acid synthetase were lower (-25 to -60%) in liver of rats fed during 45 days with a moderate long-chain triglycerides (LCT) content diet (32% of metabolizable energy, ME), than in control rats fed with a low fat diet (LCT, 10% of ME). However, the fall in malic enzyme activity was not significant. In contrast, these activities were higher (+40 to +160%) in rats fed with a diet with a moderate medium-chain triglycerides (MCT) content (32% of ME), than in control rats. Nevertheless, the increase in activity of malic enzyme and ATP citrate lyase was more important. Contrary to LCTs, MCTs had no inhibitory effect on the activity of enzymes involved in hepatic lipogenesis. PMID- 2904296 TI - Taxol reveals cortical sites of microtubule assembly in Xenopus oocytes. Role of the nucleus. AB - A binding colchicine assay together with an immunostaining study with an anti tubulin antibody showed that taxol, when added to the incubation medium, induces the formation of new microtubules in the Xenopus oocyte cortex. The capacity of the tubulin assembly in the submembranous cytoplasm decreases in progesterone matured oocytes. In contrast, in enucleated matured oocytes this change does not occur. Altogether, these results show that taxol provokes tubulin assembly exclusively in the cortex of prophase oocyte, whereas in normal matured oocytes both cortical and cytoplasmic cytaster microtubules can be induced by taxol. The swelling of the oocyte nucleus therefore controls the spatial distribution of nucleation centers for tubulin assembly during meiotic maturation. PMID- 2904297 TI - Heat-shock response in Legionella pneumophila. AB - The heat-shock response of Legionella pneumophila was examined by radiolabelling bacterial cell proteins with [35S]methionine following a temperature shift from 30 to 42 degrees C. Five heat-shock proteins were identified as having molecular masses of 17, 60, 70, 78, and 85 kilodaltons (kDa). The 85- and 60-kDa proteins were equally distributed between supernatant and pellet fractions following ultracentrifugation at 100,000 x g, the 70- and 78-kDa proteins were found primarily in the supernatant, and the 17-kDa protein was found primarily in the pellet. Synthesis of subsets of the heat-shock proteins could be stimulated by novobiocin, patulin, or puromycin. Ethanol, an effector of the heat-shock response in other microorganisms, had little effect on L. pneumophila, even at the highest concentration tolerated by the bacterial cells (1.9%). Finally, the 60-kDa heat-shock protein of L. pneumophila was immunologically cross-reactive with a polyclonal antibody prepared to the Escherichia coli groEL protein. However, a mouse monoclonal antibody reactive with the 60-kDa protein of all legionellae tested did not cross-react with the E. coli groEL protein, suggesting that the Legionella 60-kDa protein contains common and unique epitopes. PMID- 2904298 TI - Antagonistic effects of alpha-adrenoceptor blocking agents on reticuloruminal hypomotility induced by xylazine in cattle. AB - The intravenous injection of a standard dose (0.05 mg/kg) of xylazine inhibited reticuloruminal motility in cattle. Pretreatment with adrenoceptor antagonists showing alpha 2-blocking activity, tolazoline (0.5 mg/kg) and yohimbine (0.2 mg/kg), antagonized the xylazine-induced reticuloruminal amotility. Tolazoline was more effective than yohimbine, since an antagonistic effect was not seen at 0.5 mg/kg yohimbine, and yohimbine at 0.2 mg/kg was less effective than tolazoline at 0.5 mg/kg. An adrenoceptor antagonist showing alpha 1-blocking activity, prazosin, did not prevent the inhibition of reticuloruminal motility by xylazine. The xylazine-induced reticuloruminal amotility was also not prevented by either a dopamine receptor antagonist, domperidone, or an opiate receptor antagonist, naloxone. These results suggest that xylazine inhibits bovine reticuloruminal motility through its activation of alpha 2-adrenoceptors, and show that tolazoline can be used as a specific antagonist of xylazine in studies of the alpha-adrenergic influence on reticuloruminal motility in cattle. PMID- 2904300 TI - A lesson in professional development. PMID- 2904299 TI - [Tardive dyskinesia: a current review]. AB - Tardive Dyskinesia (TD) is a neurological syndrome associated with long-term use of antipsychotic drug treatment (APD). Its significant prevalence (estimated 15 20%) and potential irreversibility are a major concern in psychiatry. The clinical picture is characterized by involuntary repetitive movements of choreoathetotic and dystonic nature varying in location and intensity. The individual outcome of TD is unpredictable but recent long-term studies give reason for prudent optimism. All neuroleptics are involved in the disorder, numerous risk factors have been suggested; advancing age is the only one which has a clearly definite role. Even though several hypotheses have been suggested, the pathophysiology of the disorder remains a mystery. Informed consent is discussed in this update with regard to the legal implications of the disorder. Because of lack of effective treatment, prevention of TD is essential. The present treatment of choice is gradual reduction (and ideally discontinuance) of APD treatment when possible. PMID- 2904301 TI - [New inotropic drugs]. PMID- 2904302 TI - Ultrastructural studies on calcitonin gene-related peptide-, tachykinins- and somatostatin-immunoreactive neurones in rat dorsal root ganglia: evidence for the colocalization of different peptides in single secretory granules. AB - Calcitonin gene-related peptide (CGRP)-, tachykinins- and somatostatin immunoreactive neurones in rat dorsal root ganglia have been studied by means of single and double immunogold labelling techniques. Peptide-immunoreactive neurones are generally B- or C-type cells of small size, with well developed rough endoplasmic reticulum and scanty neurofilaments. In neurones classifiable as A2-type cells, i.e. larger neurones with a lighter cytoplasm due to the presence of poorly developed Nissl bodies and numerous neurofilaments, only CGRP immunoreactivity was detected. Immunolabelled structures were identified as large (60-100 nm diameter), electron-dense, membrane-bounded p-type granules. They were observed only in neuronal cell bodies or in the intraganglionic portions of the axons. No granules immunoreactive to the antisera applied in this study were observed in non-neuronal cells. Immuno-staining experiments with different combinations of the antisera revealed, in some cells, the presence of double immunolabelled granules; in particular localization of CGRP and tachykinins, CGRP and somatostatin, and tachykinins and somatostatin to single secretory granules was demonstrated. The finding that more than one peptide is localized to the same secretory granule supports the postulate that peptides are co-released upon nerve stimulation providing morphological support for physiological and pharmacological data demonstrating an interaction between different peptides in the modulation of synaptic activity. PMID- 2904303 TI - Layer-specific innervation of the dopamine-deficient frontal cortex in weaver mutant mice by grafted mesencephalic dopaminergic neurones. AB - The dopamine innervation of the frontal cortex originates in the A9 and A10 mesencephalic dopamine cell groups. In weaver mutant mice, there is a 77% frontocortical dopamine deficiency associated with losses of dopamine neurones in areas A9 and A10. The dopamine-depleted cortical areas of weaver mutant mice are receptive to reinnervation by afferent fibres originating in dopamine-containing mesencephalic grafts from normal donor embryos. In the anteromedial frontal lobe, reinnervation by tyrosine hydroxylase immunoreactive fibres is largely confined to the basal cortical layers whereas in the anterior cingulate cortex, tyrosine hydroxylase immunoreactive fibres also occupy superficial layers, including the molecular layer. Normally, the dopaminergic innervation of the anteromedial frontal lobe is distributed among the basal cortical layers (IV-VI), and the dopaminergic innervation of the cingulate cortex occupies both basal and superficial cortical layers. The pattern of innervation following transplantation indicates that, in repopulating dopamine-deficient cortical areas of recipient weaver mutants, graft-derived dopamine fibres show a preference for those layers which are normally invested by dopamine afferents. PMID- 2904305 TI - [Determination of desacetylmetipranolol in blood using high performance liquid chromatography with electrochemical detection]. PMID- 2904304 TI - Somatostatin-like immunoreactivity in non-pyramidal neurons of the human entorhinal region. AB - The distribution of somatostatin-immunoreactive cells and processes throughout the human entorhinal region and subjacent white matter was examined either by the unlabelled antibody-enzyme method or by the avidin-biotin method. The brain slices were obtained at autopsy with a short post-mortem delay. The majority of somatostatin immunoreactive nerve cells was found in the inner principal layer and subjacent white matter. In addition, individually scattered immunoreactive neurons were observed in both the outer principal layer and lamina dissecans. The immunoreactive perikarya varied in shape and ranged in size from 10 to 30 micron. Without exception the neurons could be classified as belonging to the group of non-pyramidal neurons. Each neuron gave rise to a few thick dendrites and a thin axon with a beaded appearance. In the adult human brain, the pattern formed by lipofuscin granules deposited in the nerve cells can be considered characteristic for the type of the neuron. Therefore, immunoreactive perikarya were documented, destained of chromogen and restained to demonstrate lipofuscin pigment and basophilic substance. It became evident from these studies that the previously immunoreactive cells were characterized by a large rounded and eccentrically located nucleus, sparse basophilic substance and, in most cases, a lack of lipofuscin granules. A few of the immunoreactive cells were laden with coarse pigment granules. The findings permit classification of entorhinal somatostatin immunoreactive neurons as either non-pigmented or pigment-laden non-pyramidal neurons. PMID- 2904306 TI - [Frequency of electroacupuncture as a cardinal factor determining the potency of analgesia and its vulnerability to naloxone blockade in rabbits]. PMID- 2904307 TI - Enzyme analysis of amniotic fluid for prenatal diagnosis of cystic fibrosis in high-risk pregnancies. AB - We determined the activity concentrations of alkaline phosphatase (ALP), ALP isoenzymes, gamma-glutamyltransferase (GGT), and alpha-glucosidase (AGL) in 1200 unselected amniotic fluids and in amniotic fluids from 40 pregnancies at high risk for cystic fibrosis (CF). From the results we established the normal range and CF-predictive cutoff values for these enzymes in the second trimester of pregnancy. In all predicted normal pregnancies that went to term, normal children were born. Among the predicted affected pregnancies, 14 were terminated and two went to term, one resulting in a CF-affected child and the other in a healthy child. Evidence for CF was found in all 13 aborted fetuses examined (the parents of one refused to allow autopsy). We noted no differences in the amniotic fluid enzyme activities for the Arab and various Jewish ethnic groups living in Israel. We conclude that prenatal diagnosis of CF among the Israeli population at risk for CF is feasible by means of a reliable, fast, and economic test in the second trimester of pregnancy. PMID- 2904308 TI - Activity of dipeptidyl peptidase IV and post-proline cleaving enzyme in sera from osteoporotic patients. AB - The activity of dipeptidyl peptidase IV (EC 3.4.14.5) in human sera from normal controls and osteoporotic patients was assayed with Gly-Pro-4-methylcoumaryl-7 amide (Gly-Pro-MCA) as substrate, at pH 8.7. The mean normal value for the activity in serum of 120 healthy subjects (ages 20-86 y) was 54.0 (SE 0.9, range 34.3-81.6) U/L at 37 degrees C and differed slightly but significantly between the younger group (less than 50 y old) and those older than 50 y. Values for the younger men were slightly but significantly higher than for the older men. Overall, however, the enzyme activities in serum were above normal in patients with osteoporosis. In contrast, the activity of post-proline cleaving enzyme (PPCE) was not increased in serum from patients with osteoporosis, as determined with succinyl-Gly-Pro-4-methylcoumaryl-7-amide (Suc-Gly-Pro-MCA) as substrate. These results suggest that high activities of dipeptidyl peptidase IV in serum of patients with osteoporosis are probably related to its severity. PMID- 2904309 TI - Reference intervals for plasma alanine aminopeptidase in the Hitachi 737 analyzer, derived from patients with normal biochemical liver profiles. PMID- 2904310 TI - Esmolol for the control of hypertension after neurologic surgery. AB - We sought to evaluate the effectiveness of esmolol vs placebo in 40 patients emerging from general anesthesia for neurosurgery. Efficacy was defined as a decrease in systolic blood pressure to within 20% above average ward pressure. The need for additional antihypertensive agents to control blood pressure was also used to define efficacy. During the infusion period 20 of 21 (95%) of the esmolol-treated patients and two of 19 (11%) of the patients receiving placebo had return of systolic blood pressure to within 20% of average ward pressure (p less than 0.001). One out of 21 (5%) esmolol-treated patients and 14 of 19 (74%) of the placebo group required intervention with additional antihypertensive medications (p less than 0.001). Esmolol was found to be effective in controlling hypertension that develops on emergence from general anesthesia in patients undergoing neurosurgery. PMID- 2904311 TI - Plasma famotidine concentration versus intragastric pH in patients with upper gastrointestinal bleeding and in healthy subjects. AB - To study the concentration-response relationship of famotidine, we serially monitored intragastric pH and measured plasma drug concentrations simultaneously after an intravenous injection of this H2-receptor antagonist (0.1 mg/kg) in eight patients with upper gastrointestinal bleeding and in six healthy subjects. By applying the sigmoidal Emax model the mean (+/- SD) plasma famotidine concentrations associated with an intragastric pH of 4.0 in patients and healthy subjects were estimated to be 17.7 +/- 10.7 and 24.8 +/- 10.3 ng/ml, respectively (not significantly different). No significant differences were observed in the mean pharmacokinetic parameters between the two study groups. Multiple regression analysis revealed that not only a pharmacokinetic factor (i.e., elimination t1/2) but also a pharmacodynamic (or sensitivity) factor (i.e., a drug concentration associated with an intragastric pH of 4.0) contributed significantly (p less than 0.01) to the overall variability in the duration of antisecretory effect in our study subjects, with standardized partial regression coefficients of 0.54 and 0.63, respectively. Based on these data, we predict that around-the-clock control of a fasting intragastric pH above 4.0 can be attained by a continuous infusion of famotidine at rates ranging from 6 to 25 mg/day (mean +/- SD, 11 +/- 7 mg/day) in a 70 kg patient whose pharmacokinetic and pharmacodynamic characteristics are similar to those of our patients. PMID- 2904312 TI - Alpha-adrenergic blockade makes minimal contribution to ketanserin's hypotensive effect. AB - Ketanserin is a selective (S2) serotonin receptor antagonist currently under investigation as an antihypertensive. It has been suggested that the antihypertensive action of ketanserin might be principally due to alpha adrenergic receptor antagonism rather than its effect on serotonin receptors. We therefore determined the contribution of alpha-adrenergic blockade to the hypotensive effects of ketanserin in six patients with hypertension and compared that with the alpha-adrenergic blockade produced by prazosin, a known alpha 1 adrenergic antagonist. Each patient received placebo, ketanserin (40 mg every 8 hours), and prazosin (5 mg every 8 hours). Each agent was administered for 4 weeks in random order. Both ketanserin and prazosin lowered blood pressure significantly and to a similar extent. The extent of alpha-adrenergic blockade was determined from the ability to inhibit the hypertensive effect of phenylephrine infusions. The dose of phenylephrine required to raise the blood pressure by 20 mm Hg was significantly higher during both ketanserin (1.41 +/- 0.27 micrograms/kg/min; p less than 0.05) and prazosin (4.99 +/- 0.77 micrograms/kg/min; p less than 0.01) administration compared with placebo (0.85 +/- 0.15 micrograms/kg/min). However, the dose ratio was more than fourfold higher during prazosin treatment (7.38 +/- 1.99; p less than 0.05) than during ketanserin (1.69 +/- 0.21). Thus at equipotent hypotensive doses the extent of alpha-blockade produced by ketanserin was more than fourfold lower than that of prazosin, implying that mechanisms other than alpha-blockade must contribute to the antihypertensive actions of ketanserin. PMID- 2904313 TI - Effect of metoclopramide on dopamine-induced changes in renal function in healthy controls and in patients with renal disease. AB - 1. The effects of intravenous metoclopramide on baseline values and dopamine dose response curves for renal haemodynamics and natriuresis were investigated in healthy volunteers and patients with renal disease. 2. Dopamine infusion alone, in doses ranging from 0.25 to 8 micrograms min-1 kg-1, resulted in a dose dependent increase in effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) with a fall in filtration fraction (FF) in eight hydrated healthy volunteers and, to a lesser degree, in 12 patients with renal disease. An increase in natriuresis (urinary excretion of sodium, UNa+V), fractional excretion of sodium (FENa+) and diuresis (urine flow rate, UV) was found in both groups for doses of 2 micrograms min-1 kg-1 and higher. 3. Metoclopramide infusion did not alter baseline values of GFR, ERPF or FF, but shifted the dopamine dose-response curve for ERPF and FF in the healthy volunteers. Metoclopramide induced a fall in UNa+V and FENa+ in both groups (fall in baseline FENa+ from 1.52 to 0.71 during metoclopramide in healthy volunteers and from 1.23 to 0.56 in patients; P less than 0.01) and blunted the natriuretic response to subsequent dopamine infusion. The fall in UNa+V during metoclopramide infusion showed a strong correlation with baseline GFR (r = -0.944). In the patients, the response for the fractional excretions of beta 2-microglobulin and gamma glutamyltransferase was comparable with that of FENa+. 4. Dopamine infusion induced a fall, and metoclopramide led to rise, in plasma aldosterone concentration. 5. We conclude that metoclopramide acts as a dopamine antagonist at the renal level in man.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2904314 TI - 1988 report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure: a commentary. PMID- 2904315 TI - [Abuse of licit drugs in heroin addicts]. PMID- 2904316 TI - [Therapy of heart failure]. PMID- 2904317 TI - [Famotidine treatment of patients with gastric and duodenal ulcers. A comparative study with once or twice-a-day administration]. PMID- 2904318 TI - [Benzodiazepine interactions with other drugs]. PMID- 2904319 TI - [Beta blocking agents in arterial hypertension: 20-year experience]. PMID- 2904320 TI - [Arterial hypertension: therapeutic trends]. PMID- 2904321 TI - [Adverse reactions to food. Notes on physiopathology, clinical features and therapy]. PMID- 2904322 TI - Physiology of the dik-dik antelope. AB - 1. The East African dik-dik antelope represents a miniature model ruminant for comparative studies. 2. Dik-diks are browsers, consuming a diet consistently high in fermentable and digestable plant material. 3. Their foregut structure is designed for a relatively rapid passage of food and effective absorption of fermentative products. 4. Dik-dik antelopes are very economical in their use of water, having a low daily water exchange and excreting a highly concentrated urine. 5. Dik-diks have been observed to employ three thermoregulatory mechanisms; thermopanting, active sweating and a labile body temperature. 6. Their reproductive cycle is polyestrous with peak breeding in June and December, having a gestation period of between 170 and 174 days. PMID- 2904323 TI - Effect of vitamin K3 on macrophage functions and intracellular calcium. AB - 1. The effect of vitamin(vit) K3 on guinea-pig macrophage functions was studied. 2. Vit K3 inhibited macrophage locomotion, phagocytosis and lysosomal enzyme release. 3. Vit K3 inhibited the rise in the intracellular free calcium level induced by stimuli at the concentration at which vit K3 suppressed functions. 4. These results suggest that vit K3 inhibits macrophage functions through the interference with the mobilization of intracellular calcium. PMID- 2904324 TI - Thermoregulatory circadian rhythms in the pouched mouse (Saccostomus campestris). AB - 1. Circadian rhythms of body temperature (Tb), oxygen consumption (VO2), and minimal thermal conductance (C) were studied in the pouched mouse, Saccostomus campestris under natural photoperiod during February at a constant ambient temperature of 28 degrees C. 2. Circadian rhythms of body temperature were also studied under natural photoperiod and laboratory temperatures (Max: 28.1 degrees C; Min: 23.2 degrees C) during February. 3. The results of the present study suggest that changes in ambient temperature are not the main "zeitgeber" for body temperature rhythm, and it seems that photoperiod plays a major role in this species. 4. The relationship between the rhythms of Tb, VO2, and C are further discussed. PMID- 2904325 TI - Changes in serum potassium concentration with exercise in Hereford calves: effects of adrenalectomy. AB - 1. Serum potassium concentration [K+] was measured pre- and postadrenalectomy in three Hereford steer calves before, during and following 3.5 min exercise at their maximal speed capability. 2. Both before and after adrenalectomy, serum [K+] increased an average of 2.4 mEq.1(-1) during exercise and was at control levels 10 min postexercise. 3. Hormones from neither the adrenal cortex nor the adrenal medulla influence serum [K+] dynamics during acute exercise. PMID- 2904326 TI - In vitro study of adrenergic stimulation of 32P incorporation into phospholipids of brown adipose tissue of control and cold-acclimated rats. AB - 1. 32P-labelled inorganic phosphate incorporation into total and mitochondrial phospholipids was studied, in vitro, on brown adipose tissue (BAT) of control and cold-acclimated rats. 2. It was found that norepinephrine acts as in vivo, on BAT phospholipid metabolism via alpha 1 adrenergic receptors specifically increasing phosphatidic acid and phosphatidylinositol turnover with the same magnitude in both groups. 3. Cold-induced alpha 1 adrenergic desensitization is not as important as cold-induced beta adrenergic desensitization. 4. No specific effect of norepinephrine was seen in mitochondrial phospholipid turnover. PMID- 2904327 TI - Reduced 125I-hGH binding by serum of dwarf pigs but not by serum of dwarfed poodles. AB - 1. Normal and growth-deficient poodle and swine strains were characterized for serum growth hormone-binding protein (GH-BP) content as well as other growth related hormones, and the relationship between these factors and body size was examined. 2. GH-BPs were found in all strains of pigs and poodles. Concentrations of GH-BPs (as expressed by specific bindings) did not vary among the poodle breeds, but did correlate with body size in pigs. 3. Insulin-like growth factors (IGFs) I and II were decreased 71 and 44% respectively in miniature compared to standard size poodles. 4. Only the Yucatan micro pig strain had reduced serum IGF I concentrations compared to normal controls. 5. Growth hormone concentrations however were normal to elevated in all micro and miniature pig strains. 6. Serum triiodothyronine concentrations were reduced in Yucatan mini and micro pigs in spite of normal circulating levels of thyroxine. 7. Body size reductions in the swine and dog strains are probably attributable to different primary defects of various growth related hormones or hormone receptors. 8. Each species breed therefore could serve as a model for a different human growth-deficient condition. PMID- 2904328 TI - Fat body involvement in vitellogenin fate in the green frog, Rana esculenta. AB - 1. Since, in Rana esculenta, fat bodies contain vitellogenin, the present study was performed in order to determine whether or not fat bodies are involved in the fate of vitellogenin. 2. The experiment of November shows that fat body excision provokes plasma vitellogenin increase even in animals treated with estradion-17 beta + pituitary crude homogenate (as compared with relative control). The same picture has been shown in the April experiment. 3. The result on protein-bound phosphate in ovaries from the April experiment has shown that fat body extirpation causes a decrease of protein-bound phosphate in the ovary. 4. This results indicates that fat bodies play an important role in sequestrating circulating vitellogenin by the ovary. PMID- 2904329 TI - Cholecystokinin (CCK) and vasoactive intestinal peptide (VIP) in the cerebral cortex of the non-hibernating and hibernating golden mantled ground squirrel. AB - 1. The effect of hibernation on cerebral cortical concentrations of cholecystokinin and vasoactive intestinal peptide was investigated in the golden mantled ground squirrel (Citellus lateralis). 2. During hibernation, cortical brain weight decreased to 83% of the non-hibernating weight. 3. The concentration of the small form of CCK was significantly reduced. The concentration of the large forms of immunoreactive CCK did not significantly change during hibernation. The molecular forms of CCK appeared the same both before and during hibernation. 4. Of note, the concentration of vasoactive intestinal peptide significantly increased during hibernation. 5. Since there was a three-fold reduction in the ratio of large to small forms of CCK during hibernation, this suggests that post-translational processing of the precursor peptides are markedly reduced during hibernation. PMID- 2904330 TI - Comparative energetics of South American cricetid rodents. AB - 1. The effects of body size, food habits and limits of endothermy on the energetics of seventeen species of South American cricetid rodents were examined. The combination of mixed diets, together with close to the expected basal rates of heat production, allows most cricetids studied to maintain effective endothermy; but those that have low basal metabolic rates and small sizes show a state of torpor. 2. Our observations do not support the hypothesis that the absence of torpor in South American cricetid rodents is due to phylogenetic characteristics. 3. The high ecological diversity, as well as the variety of life modes of these rodents, is explained on an energetic basis. PMID- 2904331 TI - Mammary blood flow and cardiac output during initiated involution of the mammary gland in the rabbit. AB - 1. Cardiac output and its distribution to the mammary gland, kidneys, heart, liver and gastrointestinal tract were measured in conscious rabbits at day 1, day 3 and day 6 after removal of the young at day 0. 2. There was no change in cardiac output, proportion of cardiac output delivered to the mammary gland or mammary blood flow 24 hr after the last suckling period. After a further 48 hr there was a significant reduction in the cardiac output, proportion of the cardiac output and blood flow to the mammary gland compared to the values measured in lactating animals. 3. There was no significant difference in blood flow to the other organs although there were changes in the proportion of the cardiac output delivered to the heart, kidney and liver during this period. 4. The change in uptake of glucose, acetate, non-esterified fatty acids and triacylglycerols by the mammary gland are discussed in relation to the reabsorption of milk components. PMID- 2904332 TI - Taurine transport across the small intestine of adult and suckling rats. AB - 1. Taurine accumulation in intestinal cells of adult and suckling rats reached steady-state after 60 min with an In/Out ratio of 1.46 and 4.66 in the adult and suckling rats respectively. 2. The accumulative capacity of the intestinal strips isolated from suckling rats is almost four times higher than that of adult rats. 3. The steady-state uptake of taurine by the adult and suckling rats intestinal cells is saturable, sodium-dependent and inhibited by ouabain. 4. The calculated Vmax of the mediated component of the steady-state uptake in the suckling rats is three times greater than that of the adult rats, and the affinity is seven fold greater in the suckling as compared to the adult. 5. Taurine influx across the mucosal membrane in the suckling rat is significantly greater than that of the control adult. PMID- 2904333 TI - Role of sodium on H+ excretion in the integument of the leopard frog Rana pipiens. AB - 1. The northern leopard frog, Rana pipiens, pipiens, in contrast to the southern leopard frog, Rana pipiens, berlandieri, did not demonstrate any significant H+ excretion across its integument even during a challenge of chronic metabolic acidosis. Likewise, no increase in the number of H+ secreting mitochondria-rich cells were observed in the northern frogs. 2. Under normal acid-base conditions in the southern frogs, H+ excretion was found to be dependent on mucosal sodium concentrations, whereas during chronic metabolic acidosis, H+ excretion was independent of mucosal sodium concentrations, but was amiloride sensitive. 3. High salinity adapted southern frogs, under normal and acidotic conditions, had enhanced H+ excretion rates as compared to the control non-salt adapted frogs. 4. Blood analyses demonstrated that significant acid-base changes were the result of systemic acidosis and not due to salt adaptations. Blood Na+ and K+ concentrations were also efficiently maintained during salt adaptations or chronic metabolic acidosis. 5. The results suggest that H+ excretion in epithelia can be influenced by the sodium transport state of the cell and the systemic acid base profile. Models are proposed explaining these relationships. PMID- 2904334 TI - Effect of early feed restriction in male broiler chicks on plasma metabolic hormones during feed restriction and accelerated growth. AB - 1. Plasma GH was greater (P less than 0.05) on day 12 in ad libitum-fed birds compared to restricted chicks. Conversely, maximum GH levels were found to occur in the nutrient restricted chicks during the period of accelerated growth (day 42). 2. A significant decline in circulating insulin concentrations with advancing age was evident in both ad libitum-fed and restricted chicks. 3. Feed restriction significantly suppressed circulating T3 in restricted chicks, with concentrations returning to control levels upon refeeding. 4. A significant increase in T4 with advancing age was evident in both treatment groups, with T4 being significantly greater in controls compared to restricted chicks at 54 days of age. PMID- 2904336 TI - Prevention of cancer: restriction of nutritional energy intake (joules). AB - 1. The reduction of nutritional energy intake (joules) often reduces the incidence of both spontaneous and induced cancers in humans and experimental animals in an approximately dose-dependent manner. 2. To achieve the best preventive effect, the reduction of dietary intake should begin well before the carcinogen insult, should be intense enough (lowering the intake of joules by at least approx. 25-30%) and should last a long time, preferably even life-long. 3. This preventive effect depends upon the strain, sex and age of animals, the kind of carcinogenic insult and also the susceptibility of the target tissue. 4. The mechanism by which the dietary restriction may exert its protective action may involve changes in the hormonal equilibria, influences upon the immuno surveillance, changes of activities of enzymes involved in carcinogen metabolism and other factors. 5. Since over-eating and the resulting obesity constitutes a pronounced risk factor for the incidence of cancer and other diseases, lowering the nutritional energy intake represents today the simplest, cheapest and most effective way to prevent cancer in the general population. PMID- 2904335 TI - The role of aldosterone in water and electrolyte transport across the colonic epithelium of the lizard, Gallotia galloti. AB - 1. The effects of D-aldosterone on the electrical properties and ionic transport have been analysed (in vitro) in the colonic epithelium of the lizard, Gallotia galloti. 2. The injection of 30 g of D-aldosterone induced a significant rise of plasma aldosterone concentration, sustained for 4 hr after administration. 3. Intraperitoneal injections of D-aldosterone caused a slight reduction of transmural potential difference (PD) and short-circuit current (Isc). 4. Net absorption of Na+ across the colon from aldosterone-treated lizards did not increase when compared to colon from normal lizards. Cl- absorption was increased in treated lizards. 5. Addition of mucosal barium to treated tissues brought about a sustained increase of PD and Isc. 6. The absorption of fluid in normal lizards was reversed to fluid secretion in treated lizards. 7. The effects of D aldosterone on lizard colon are compared with those reported for the colon of mammals and birds. PMID- 2904337 TI - Oxygen toxicity is not related to mammalian body size. AB - 1. Small mammals have been used to study the effects of O2 toxicity. The aim of the present study was to investigate whether body size should be considered when applying the results of these studies to man. 2. Oxygen toxicity is enhanced as perfusion and metabolism increase: specific animal tissues of high perfusion are more susceptible to O2 toxicity. Exercise, high metabolic rate, and increased brain blood flow enhance O2 toxicity. 3. Increased specific O2 consumption and perfusion as body mass decreases may enhance O2 toxicity in small mammals. 4. Survival time in normobaric hyperoxia (1 atm O2) and the time to first appearance of convulsions in hyperbaric oxygen (4-5 atm) were collected from the literature and showed no relation to body size. 5. Known difference in antioxidant enzyme activity cannot explain the findings. 6. Independence of tissue PO2 on body size, or equal rates of free radical formation and degradation, are suggested as possible mechanisms. 7. Small mammals can serve as a good model for O2 toxicity in man. PMID- 2904338 TI - Low-sodium contractures indicating sarcolemmal Na/Ca-exchange in the frog heart. AB - 1. In the frog heart, Ca2+ enters the cell by the slow inward current (Isi) and by an electrogenic, carrier-mediated, and passive Na-out/Ca-in-exchange. 2. The latter reverses to Na-in/Ca-out-exchange during depolarization and thereby controls relaxation. 3. The exchange ratio is 3 Na+ for 1 Ca2+. 4. The Na/Ca exchange is not inhibited by organic Ca-antagonists in frog myocardium, indicating that the initiation of the heart beat may mainly depend on Isi. 5. This is not necessarily in contradiction with the Na-Ca-antagonism, since there also exists an antagonism between Na+ and Ca2+ in the slow channel. 6. However, the contractures caused by a decrease of NaO+ are mediated by the Na/Ca-exchange. PMID- 2904340 TI - A long term survey of plasma and tissue ferritin in mice fed on iron deficient diets. AB - 1. Changes in plasma and tissue ferritin concentrations were surveyed in mice fed on iron deficient diets (Fe, 2.4 micrograms/g) from the age of 8 to 30 weeks by an enzyme-immunoassay for mouse ferritin. Values were compared with those in mice on control diets (Fe, 110 micrograms/g) and mice with blood loss. 2. In mice on iron deficient diets, while plasma ferritin remained at normal level, ferritin in the spleen and kidney decreased, but that in the liver increased as much as twice of that in the control. 3. Mice with blood loss revealed a drastic reduction of ferritin in every tissue and plasma examined. PMID- 2904339 TI - Mitotic activity of stomach epithelium in the ground squirrel, Citellus erythrogenys Brandt. AB - 1. During hibernation the epithelial cells of the stomach in ground squirrels divide upon spontaneous emergence from hibernation. In torpor periods, mitoses are blocked up. 2. In animals which have come out of hibernation in spring, one peak of mitosis has been recorded in the first few hours after emergence, and another 3 or 4 days later. 3. In summer the mitotic index is low. PMID- 2904341 TI - Regulation of energy economy in raccoon dogs and blue foxes: a process of dynamic interactions. AB - 1. Seasonal regulation of energy economy was studied in farm-raised blue foxes (Alopex lagopus) and raccoon dogs (Nyctereutes procyonoides; Gray, 1834). 2. Both species exhibited marked seasonal changes in body weight, body energy content, food intake and locomotor activity. Seasonal changes in food efficiency were also evident. 3. The results emphasize the important role of both energy intake and energy expenditure in the regulation process. 4. It can be concluded that regulation of seasonal energy balance is a dynamic process with various interactions between different factors. PMID- 2904342 TI - Interactive effects of live weight, basal diet and fat supply on essential fatty acid status and blood concentrations of glucose, insulin and thyroxine measured postprandially in pigs. AB - 1. The composition of the basal diet (purified vs complete feed ingredients provided as a cassava and a barley based diet, respectively), type of dietary fat [saturated fatty acids (18:0) supplied as fully hydrogenated soya bean oil vs unsaturated fatty acids (18:2) supplied in the form of soya bean oil] and the live wt of the animals (40 vs 80 kg) highly influenced the EFA status of the body and postprandial blood concentrations of glucose, insulin and thyroxine. 2. Interactive effects of live wt, type of basal diet and fat supply on EFA status and postprandial blood levels are discussed. PMID- 2904343 TI - Use of fibre-optic endoscopes in studies of gastric digestion in carnivorous vertebrates. AB - 1. Two methods of assessing gastric digestion rates of three prey types fed to Sooty albatrosses Phoebetria fusca were compared: removal of stomach contents, using a water-flushing stomach pump (a technique used commonly in diet studies), and inspection using a fibre-optic gastroscope (a previously unused technique). 2. The stomach pump yielded quantitative information, but proved stressful and resulted in incomplete recovery of meals ingested 3-6 hr before pumping. Gastric morphology of the animals studied and digestion state of their stomach contents may influence the effectiveness of this technique. 3. Inspection using the gastroscope yielded qualitative information only but permitted serial inspection of the same animal, and was less stressful than the stomach pump. Times for total evacuation of the stomach were 6-12 hr less when estimated using the gastroscope than when using the stomach pump. 4. The specifications of endoscopes relevant to their use by biologists are given. 5. Previous non-medical biological uses of endoscopes are given. Potential uses include underwater observations, sampling of digestive juices and stomach linings for enzyme analyses, observations of ingested prey, and assessment of parasite infestation. PMID- 2904344 TI - Calcium and olfactory transduction. AB - 1. Inorganic cations, organic calcium antagonists, and calmodulin antagonists were applied to olfactory epithelia of frogs (Rana pipiens) while recording electroolfactogram (EOG) responses. 2. Inorganic cations inhibited EOGs in a rank order, reflecting their calcium channel blocking potency: La3+ greater than Zn2+ greater than Cd2+ greater than Al3+ greater than Ca2+ greater than Sr2+ greater than Co2+ greater than Ba2+ greater than Mg2+. Barium ion significantly enhanced EOGs immediately following application. 3. Diltiazem and verapamil produced dose dependent EOG inhibition. 4. Calmodulin antagonists inhibited EOGs without correlation to their anti-calmodulin potency. PMID- 2904345 TI - Serum alpha-tocopherol, all-trans retinol, total lipids and cholesterol in the black rhinoceros (Diceros bicornis). AB - 1. Mean concentration of serum alpha-tocopherol (Vitamin E) in 28 free-living black rhinoceroses sedated during translocation in Zimbabwe was 1.92 (SD, 0.43) mg/l. 2. Alpha-tocopherol was not detectable (less than 0.15 mg/l) in five captive black rhinoceroses held at London Zoo. 3. Circulating levels of all-trans retinol (Vitamin A) were not different between the two groups. 4. The low level of alpha-tocopherol in captive rhinoceroses suggests a risk of acute haemolytic anaemia. PMID- 2904346 TI - Fiber type composition of the plantarflexors of giraffes (Giraffa camelopardalis) at different postnatal stages of development. AB - 1. A sample of fibers from deep (close to the bone) and superficial (away from the bone) regions of the plantaris (PLT) and medial (MG) and lateral (LG) gastrocnemius muscles of a neonatal, a 17-day-old and an adult giraffe were typed qualitatively as dark or light based on alkaline preincubation myosin ATPase staining properties and then sized. 2. Each muscle at all ages showed a higher percentage and a larger cross-sectional area (CSA) or light ATPase fibers in the deep than the superficial region. This relationship was qualitatively, although not quantitatively, similar to that reported in hindlimb muscles of other mammals. 3. At all ages, the PLT, the deepest muscle in the synergistic group, had the highest relative total CSA of light ATPase fibers among the muscles sampled. 4. At birth, the PLT had an unusually high percentage of light ATPase fibers in comparison to that found in the same muscle of other mammals. With age, the total CSA of light ATPase fibers increased dramatically in the PLT and decreased slightly in the MG and LG. 5. These data suggest that the PLT, especially the deep portion, may functionally replace the soleus muscle which is absent in the giraffe. In addition, the fiber type results demonstrate that the changes in the fiber type composition of individual muscles observed at different postnatal ages in the giraffe are relatively similar to that reported in smaller mammals, suggesting the existence of similar regulatory mechanisms. PMID- 2904347 TI - Regulation of glucose uptake in rat slow and fast skeletal muscles. AB - 1. Regulation of glucose uptake was compared between extensor digitorum longus (EDL) and soleus (Sol) muscles in rats. 2. Insulin stimulated glucose uptake more in EDL than in Sol. 3. Under high concentrations of insulin, the glucose uptake was higher in EDL than Sol. 4. Inhibition of oxidative phosphorylation by anoxia or an uncoupler stimulated glucose uptake more in EDL than in Sol. 5. Anoxia abolished the effect of insulin on glucose uptake in both EDL and Sol. 6. The blocker to glucose transport system reduced glucose uptake more in Sol than in EDL. PMID- 2904348 TI - Effect of propranolol in combination with TSH and ovine prolactin on plasma thyroid hormone levels and in vitro hepatic monodeiodination of thyroxine in brook charr, Salvelinus fontinalis (Mitchill). AB - 1. Ovine TSH stimulated an increase in plasma T4 levels in brook charr, but plasma T3 levels, hepatic T3 content and hepatic T4-monodeiodination to T3 were unaffected. TSH-induced plasma T4 levels were further enhanced in propranolol pretreated fish. 2. Fish treated with ovine prolactin + TSH had elevated plasma T3 levels, hepatic T3 content and hepatic T4-monodeiodination rates compared with TSH-treated animals. Propranolol-pretreatment further enhanced hepatic T4 monodeiodination in these fish. 3. Propranolol, a beta-adrenoceptor blocker, appears to enhance peripheral T4 to T3 conversion in physiological situations when plasma thyroid hormone levels and T4-monodeiodination rates are high. PMID- 2904349 TI - Deletions in human chromosome arms 11p and 13q in primary hepatocellular carcinomas. AB - Normal liver and hepatocellular carcinoma (HCC) genotypes were compared at loci on most of the human chromosomes with probes that detect restriction fragment length polymorphisms. Six of fourteen tumors exhibited loss of heterozygosity of one or more markers on 11p. Ten patients were informative for loci on 13q, and 5 of these 10 exhibited loss of heterozygosity for one or more of the 13q markers. Altogether, 9 of the 14 patients showed loss of a polymorphic allele for one or more loci on either 11p or 13q. A survey of loci on 16 additional chromosomes indicated that the deletions were not due to a general loss of heterozygosity in HCCs. Quantitative densitometry showed that each of the 10 deletions resulted in hemizygosity (no reduplication) of the remaining allele in tumor tissue. In contrast to hereditary embryonal tumors, in which reduplication of the remaining chromosome is the rule, simple deletion appears to be the primary mechanism responsible for the loss of heterozygosity in these adult, nonhereditary HCCs. These data show that HCCs arising in hepatitis B virus carriers are a genetically heterogeneous group of tumors, some of which may arise through 13q alterations, some through 11p alterations, some with both chromosomes altered, and some with both intact. PMID- 2904350 TI - [Humoral substances in peripheral and portal veins in cirrhotic patients]. PMID- 2904351 TI - [Micro-surgical anatomical study and clinical use of the scapular flap with nerves]. PMID- 2904352 TI - Gastric luminal somatostatin secretion of normals and patients with pernicious anemia and with Zollinger-Ellison syndrome. AB - We studied the release of gastric luminal somatostatin-like immunoreactivity (SLI) in response to a pentagastrin infusion (0.9 microgram/kg/hr, intravenous) in five normal volunteers, five patients with pernicious anemia, and two patients with Zollinger-Ellison syndrome. In addition, we studied the gastric luminal SLI secretion in response to a gastric luminal acid perfusion in two patients with pernicious anemia. Our results have shown that: (1) pentagastrin caused a parallel increase in luminal hydrogen ions and SLI release in normal volunteers; (2) Zollinger-Ellison patients had elevated basal acid and SLI levels that did not increase further with pentagastrin; (3) pentagastrin did not increase gastric acid or luminal SLI secretion in pernicious anemia patients; and (4) in pernicious anemia patients, a gastric luminal acid perfusion caused a significant increase in gastric luminal SLI over baseline values. In conclusion, gastric luminal hydrochloric acid appears to be a factor which stimulates the secretion of luminal SLI in human beings. PMID- 2904354 TI - Mouse homeobox gene transcripts occupy different but overlapping domains in embryonic germ layers and organs: a comparison of Hox-3.1 and Hox-1.5. AB - By use of in situ hybridization experiments, the mouse homeobox genes Hox-3.1 and Hox-1.5 are compared in the temporal and spatial patterns of their embryonic transcripts. Transcripts of both genes are first detected at about 7 1/2 days, although the appearance of Hox-3.1 transcripts apparently follows Hox-1.5 after a small delay. Hox-3.1 and Hox-1.5 transcripts occupy domains which are different, although overlapping, along the anteroposterior axis of the embryo. The domains are first established within the ectoderm and mesoderm germ layers at 7 1/2-8 days, but subsequently they persist within the nervous system, the prevertebral column and within at least some of the organs (the thyroid, lung, stomach, mesonephric and metanephric kidneys) at 12 1/2 days. In discussion, two different mechanisms are considered by which positional information might first be generated within the germ layers. PMID- 2904355 TI - [A scale for evaluating withdrawal symptoms induced by anxiolytic agents]. AB - A scale to evaluate the withdrawal syndrome induced by tranquilizers (TWS) is proposed to distinguish between anxiety induced symptoms and withdrawal induced symptoms. This scale was established and validated by Lader, the french translation was performed by the author. The most frequently observed symptoms during a withdrawal syndrome are physical tiredness, headache, vertigo and tremor but other symptoms are evaluated by this tranquilizers withdrawal scale. PMID- 2904353 TI - Clinical use of serum enzymes in liver disease. AB - Some of the many enzymes found in hepatocytes can be measured in the serum and are used as tests of liver function. We now review the current knowledge of their physiology and pathophysiology and outline their clinical usefulness. We divide them into two categories: enzymes that primarily reflect cholestasis, such as the alkaline phosphatase, the 5'-nucleotidase, and the gamma-glutamyl transpeptidase, and those that primarily reflect hepatocellular necrosis, such as the aminotransferases. We also briefly discuss several enzymes of more limited usefulness. PMID- 2904356 TI - [Retrospective comparative study of treatment with delayed-action neuroleptics and neuroleptics administrated orally in long-term psychosis]. AB - Through a retrospective study, we have tried to compare the indication spectrum and efficacy of depot neuroleptics versus oral neuroleptics on two hundred patients suffering from long term psychosis. For each group, we selected one hundred patients who met the following requirements: the minimal duration of chemotherapy was of 3 years, the patients were aged 16 to 60. Patients receiving depot neuroleptics, although their original prognosis were worse than those of patients receiving oral neuroleptics, obtained the same good results concerning most semiological, chemotherapeutic and institutional criteria. However, good results for patients receiving depot neuroleptics must be qualified because of a more important number of chronic and defect states and a lack of autonomy. PMID- 2904357 TI - Antipeptide antibodies recognize c-erbA and a related protein in human A431 carcinoma cells. AB - Peptides corresponding to the deduced amino acid residues 15-29 of the amino terminal region and 445-456 of the carboxyl-terminal region of the human placental c-erbA protein (hc-erbA-beta) were synthesized and used to produce site specific rabbit polyclonal antipeptide sera. Antibodies to the carboxyl-terminal peptide (C-91) and the amino-terminal peptide (N-98) specifically immunoprecipitated the hc-erbA-beta proteins synthesized in vitro. Furthermore, 68% and 48% of the T3-binding activity of the hc-erbA-beta protein were immunoabsorbed by antibodies C-91 and N-98, respectively. These results indicate that C-91 and N-98 recognized hc-erbA-beta proteins. These antibodies were used to study the subcellular distribution of hc-erbA-beta protein in human cultured cells. Nuclear extracts were prepared from human A431 carcinoma cells; C-91 immunoabsorbed 50% of the specific T3-binding activity in these extracts. These results provide structural evidence to confirming that hc-erbA-beta is the T3 nuclear receptor. Cells were metabolically labeled with [35S]methionine, and the cytosolic extracts were immunoprecipitated by C-91 or N-98. A protein with a mol wt of 58,000 (Cp58) was specifically immunoprecipitated by N-98 or C-91. Peptide mapping by V8 digestion and cyanogen bromide cleavage showed that the Cp58 molecules immunoprecipitated by N-98 or C-91 was identical. Indirect immunofluorescence using N-98 or C-91 indicated that Cp58 is present exclusively in the cytoplasm. Other human cultured cells, HepG2, MCF-7, IM-9, and KB, were also evaluated, and similar results were found. These results raised the possibility that a precursor of hc-erbA-beta may be present in the cytosol. The functional significance of the hc-erbA-beta-related cytosolic Cp58 remains to be established. PMID- 2904358 TI - Somatostatin-28 does not regulate islet function in the dog. AB - Somatostatin-28 (S-28) is a naturally occurring N-terminally extended form of the tetradecapeptide somatostatin (S-14). The concept has arisen that S-28 is a gut hormone that regulates insulin secretion. This concept is based on 1) reports that S-28 is a more potent inhibitor of insulin secretion than S-14; 2) the finding that S-28 is present in D-cells of the intestine and is released after a meal; and 3) the demonstration of selective binding of S-28 to B-cells of the rat islet. To critically test this hypothesis we have 1) measured the circulating levels of somatostatin-like immunoreactivity (SLI) during infusions of S-28 and S 14 to accurately compare their potencies to inhibit insulin and glucagon secretion from the in vivo dog pancreas, and 2) measured the circulating levels of endogenous SLI released after a meal and compared these to the circulating levels of infused S-28 needed to inhibit insulin secretion. Infusion of S-28 at rates of 170 and 500 pmol/min raised arterial SLI levels by 282 +/- 26 and 885 +/ 98 fmol/ml, respectively. Immunoreactive insulin (IRI) output was inhibited by 20 +/- 11% (P less than 0.05) and 52 +/- 7% (P less than 0.0005), respectively. Immunoreactive glucagon (IRG) output was not significantly altered by either dose. Pancreatic SLI output was inhibited by 32 +/- 5% (P less than 0.0005) by the 500 pmol/min infusion. Infusion of S-28 at 50 pmol/min increased arterial SLI by 108 +/- 17 fmol/ml, but did not alter IRI output (+4 +/- 20%). In comparison, infusion of S-14 (100 pmol/min) raised arterial SLI levels by a similar amount (110 +/- 21 fmol/ml), but, unlike S-28, inhibited both IRI (-50 +/- 6%, P less than 0.0005) and IRG output (-17 +/- 8%; P less than 0.05). Thus, comparable increments in arterial S-28 failed to reproduce the inhibition of IRI secretion seen during the S-14 infusion, while similar inhibition was seen with an 8-fold increment. This suggests that S-28 is significantly less potent than S-14 in the dog. After a mixed meal, endogenous SLI levels increased by 35 +/- 3 fmol/ml in arterial plasma.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2904359 TI - Attenuation of anterior pituitary phosphoinositide phosphorylase activity by the D2 dopamine receptor. AB - We have examined the influences of dopamine and the D2 receptor agonist bromocriptine on phosphoinositide metabolism in primary cultures of rat anterior pituitary cells, monitoring changes in the levels of phosphatidylinositol (PtdIns), phosphatidylinositol-4-phosphate [PtdIns(4)P], and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2]. Basal incorporation of [3H]inositol ([3H]Ins) into phosphoinositides was progressive, and radioisotopic equilibrium was attained in all three species within 48 h. The inclusion of dopamine or bromocriptine in the incubation medium promoted concentration-dependent reductions in the rate, but not the magnitude, of phosphoinositide radiolabeling. The onset of this effect was rapid; inhibition of [3H]Ins incorporation by dopamine (500 nM) and bromocriptine (100 nM) could be detected within 2 h. This treatment also produced a comparable reduction in the incorporation of [32P]orthophosphate into PtdIns(4,5)P2. In extended time-course studies, bromocriptine dramatically retarded the radiolabeling of PtdIns(4)P and PtdIns(4,5)P2, and apparent equilibria in these species were attained only after 96 h. We also assessed the ability of dopamine to modify the concentration response characteristics of [3H]Ins-labeled inositol phosphate ([3H]InsPx) production by TRH, angiotensin II (AII), neurotensin (NTS), bombesin (BBS), and vasoactive intestinal polypeptide (VIP). Neither dopamine nor bromocriptine altered the rate or magnitude of TRH-, AII-, NTS-, or BBS-related InsPx generation. VIP was completely ineffective in stimulating InsPx generation. PRL release was significantly reduced in all dopamine-treated groups. That the InsPx concentration-response relationships for each of these peptides remained unimpaired by exposure to dopamine or bromocriptine extends our previous observation that the phosphoinositide-specific phospholipase-C is insensitive to dopaminergic tone. Consistent with our earlier findings, these data indicate that activation of the D2 dopamine receptor attenuates the activity of mechanisms associated with the serial phosphorylations of PtdIns and PtdIns(4)P, reactions that give rise to PtdIns(4)P and PtdIns(4,5)P2, respectively. It is our conclusion that dopamine, in addition to its other actions, attenuates the phosphorylation, rather than the hydrolysis, of anterior pituitary phosphoinositide. This attenuation appears to be mediated by an inhibitory coupling of the D2 receptor with the phosphoryltransferase activities that catalyze PtdIns(4)P and PtdIns(4,5)P2 formation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2904360 TI - Testosterone restores testicular inhibin content in cryptorchid rats. AB - The effects of testosterone administration on testicular inhibin content and histology were studied in bilaterally cryptorchid rats, in which a marked decrease in testicular inhibin content had been observed. Mature male Wistar rats weighing approximately 300 g were made bilaterally cryptorchid by placing the testes in the abdominal cavity. Testosterone in oil, 0.1, 1.0 or 10 mg, was given i.m. each week. Testicular inhibin and testosterone content, histology and plasma LH, FSH and testosterone were studied 2 weeks later. Abnormally decreased testicular inhibin in cryptorchidism was restored toward normal by testosterone in a dose dependent manner in 2 weeks after surgery. Sertoli cell structure also recovered toward normal with increasing amount of testosterone. Decreased testicular testosterone content and Leydig cell atrophy were observed with suppressed plasma LH and FSH after testosterone. These results showed that the increased plasma concentration of testosterone had a stimulatory effect on the Sertoli cell function in cryptorchidism, in which compensated Leydig cell failure was demonstrated. PMID- 2904361 TI - Epileptiform activity induced by lowering extracellular [Mg2+] in combined hippocampal-entorhinal cortex slices: modulation by receptors for norepinephrine and N-methyl-D-aspartate. AB - Reduction of extracellular Mg2+ concentration induced spontaneous and evoked epileptiform activity in the entorhinal cortex (EC) and dentate gyrus (DG) of combined hippocampus (HC)-EC slices. Extracellular field potentials, as well as changes in extracellular Ca2+ and K+ concentrations, were measured in EC and DG with ion-selective/reference electrodes during both repetitive and single stimuli. In the EC, lowering extracellular [Mg2+] induces both spontaneous and single stimulus evoked ictal events consisting of extracellular negative potential shifts (up to 5 mV, 30 sec), decreases in [Ca2+]0 and increases in [K+]0. In the DG, spontaneous events were much shorter, but similar changes in [Ca2+]0, [K+]0 and field potentials (FPs) could be evoked by brief high-frequency stimulation. In both areas, the N-methyl-D-aspartate (NMDA) receptor antagonist 2 aminophosphonovalerate (2-APV) completely blocked spontaneous as well as stimulus evoked epileptiform events. The neurotransmitter norepinephrine (NE), which has previously been shown to modulate long-term potentiation in the DG, was found to exhibit differential modulation of epileptiform activity in the EC and DG. In the EC, NE, acting via alpha 1-receptors, completely blocked low Mg2+-induced epileptiform activity. In contrast, in the DG, NE exhibited a beta-receptor mediated prolongation of the low Mg2+-induced ictal events, and enhanced the stimulus-induced ionic and field potential changes. From these results, we conclude that lowering extracellular [Mg2+], acting in large part through the removal of the Mg2+ voltage-dependent blockade of NMDA receptors, leads to induction of epileptiform activity in both the EC and DG.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2904362 TI - Differences between seizure-prone and non-seizure-prone mice with regard to glutamate and GABA receptor binding in the hippocampus and other regions of the brain. AB - Quisqualate-preferring glutamate receptors were determined in membranes from frontal cortex, occipital cortex, hippocampus and cerebellum, from seizure-prone DBA/2J BOM and seizure-resistant C57/BL mice. The animals were studied 21, 27 and 40 days postnatally, i.e., before, during and after the age at which DBA mice are most susceptible to seizures. Radio-binding assays were performed using [3H]AMPA in the presence of 100 nM glutamate. Except for the occipital cortex, where no significant differences between the two strains were observed, all areas of the brain of DBA mice exhibited significantly (P less than 0.001, t test) higher AMPA binding than the corresponding areas of C57/BL mice at 27 days of age. At pre- and post-susceptible ages, the two strains showed no significant differences in the hippocampus and occipital cortex. A significant difference was observed, however, in the frontal cortex and cerebellum at the ages of 21 and 40 days, respectively, although this difference was considerably less than at 27 days. In addition to determination of glutamate receptors, GABA-receptor binding was also studied in membranes from the same cerebral areas and at the above-mentioned ages. Binding characteristics, using [3H]GABA as the ligand, were essentially identical in the two strains at all ages investigated, i.e., both low and high affinity GABA receptors could be identified with KD values of 6-16 nM and 100-800 nM, respectively. PMID- 2904363 TI - Effect of cortical kindling on [3H]D-aspartate uptake and glutamate metabolism in rats. AB - The effects of cortical kindling in rats on [3H]D-aspartate uptake and on glutaminase and glutamine synthetase activities has been studied. The high affinity uptake of [3H]D-aspartate in control cortical tissue (Km approximately 2 microM) was undetectable in the kindled tissue, whilst the enzyme activities were unchanged. A loss of the high-affinity uptake sites for excitatory amino acids may be a contributing factor to the kindling phenomenon. PMID- 2904364 TI - Increased levels of amino acid neurotransmitters in the inferior colliculus of the genetically epilepsy-prone rat. AB - Previous studies have shown an increase in the number of GABAergic and total neurons in the inferior colliculus (IC) of the genetically epilepsy-prone rat (GEPR). Amino acid analysis of the central nucleus of the IC, as well as cerebellum, sensorimotor, temporal, and occipital cerebral cortices of GEPRs with high pressure liquid chromatography showed significant increases in the levels of GABA, taurine and glutamate. The IC of GEPR displayed a 2.3-fold increase in GABA as compared to that of non-epileptic rats, a 2.4-fold increase of taurine, and a 1.9-fold increase of glutamate. In addition, taurine and glutamate were increased in the sensorimotor and temporal cortex, respectively. These results are consistent with previous anatomical data on the GABAergic system in the IC and provide additional information. The increase in taurine and glutamate in the IC indicates that other neurotransmitters could be involved in the mechanism of seizure activity. PMID- 2904365 TI - Suppression of ictal-like activity by kynurenic acid does not correlate with its efficacy as an NMDA receptor antagonist. AB - The involvement of excitatory amino acid (EAA) receptors in ictal-like activity was investigated using hippocampal slices from immature rats. Bath application of kynurenic acid (KYN) suppressed penicillin-induced synchronized afterdischarges. An identical concentration of D(-)2-amino-5-phosphonovaleric acid (D(-)AP5) spared the afterdischarges. Intracellular recordings confirmed D(-)AP5 to be the more potent N-methyl-D-aspartate antagonist. KYN's suppression of afterdischarges could not be clearly attributed to blockade of either kainate or quisqualate receptors. Thus, a novel kynurenate-preferring EAA receptor may play an important role in seizure generation in immature hippocampus. PMID- 2904366 TI - The role of neurotransmitters and opioids in polycystic ovarian syndrome. AB - In this article, the characteristic gonadotropin dysfunction of PCOD is discussed. The potential role of modulators such as the neurotransmitters dopamine and norepinephrine as well as the role of endogenous opiates are considered. A review of the effect of these neuromodulators is followed by speculation as to whether disordered secretion of these substances may be operative in the pathophysiology of PCOD. PMID- 2904367 TI - Administration of vecuronium, atracurium and pancuronium in divided doses: effect on onset and duration of action. AB - The time to onset of neuromuscular block (as assessed by single twitch stimulation at 0.1 Hz) and the duration to 25% recovery of twitch height were measured after administration of vecuronium 0.1 mg kg-1, atracurium 0.5 mg kg-1 or pancuronium 0.1 mg kg-1, administered either as a single bolus or in divided doses, 10% being administered 4 min prior to the remaining 90%. The patients were anaesthetized with thiopentone, nitrous oxide in oxygen and i.v. fentanyl. There was no significant difference between the single- and divided-dose groups, either in the onset times (2.8 and 2.9 min for vecuronium, 2.7 and 2.4 min for atracurium and 3.3 min each for pancuronium for single- and divided-dose groups, respectively) or the duration to 25% recovery of twitch height (35 and 29 min for vecuronium, 45 and 39 min for atracurium and 87 and 93 min for pancuronium for single- and divided-dose groups, respectively). PMID- 2904368 TI - Hormone-sensitive adenylate cyclase of prolactin-producing rat pituitary adenoma (GH4C1) cells: molecular organization. AB - Hormonal activation and inhibition of the GH4Cl1 cell adenylate cyclase complex is delineated. In the presence of the guanyl nucleotide GTP, enzyme activity was enhanced twofold by thyroliberin, sixfold by vasoactive intestinal peptide (VIP), twofold by prostaglandin E2 and twofold by isoproterenol. The diterpene, forskolin, increased, the activity 14-fold. In the presence of high GTP (400 microM) and NaCl (150 mM) concentrations, somatostatin inhibited (ED50 = 0.5 microM) the cyclase activity by 40%. In the presence of 10 microM somatostatin, the ED50 values (5 nM) for thyroliberin- and VIP-stimulated adenylate cyclase activities were shifted to 20 nM. Forskolin-elicited activation was, however, not affected by somatostatin. Cholera-toxin and pertussis-toxin pretreatment of the enzyme brought about some 20-fold and twofold activation, respectively. Inhibition by somatostatin was abolished upon pre-exposure to pertussis toxin. Mild alkylation by N-ethylmaleimide increased basal and hormone-activated adenylate cyclase while somatostatin again failed to express its inhibitory potential. Further alkylation caused a gradual decline and convergence of hormone modulated cyclase activities towards zero. The N-ethylmaleimide-induced attenuation of thyroliberin-elicited activity was paralleled by a decrease in [3H]thyroliberin binding. Trifluoperazine and an anti-calmodulin serum reduced basal and net thyroliberin-, VIP- and forskolin-enhanced cyclase activities by some 30%, 100%, 70% and 80%, respectively. The Vmax of basal and thyroliberin stimulated adenylate cyclase was diminished by 65%, leaving the apparent Km values (7.2 mM and 2.6 mM, respectively) for Mg2+ unaltered. Finally, the phorbol ester 12-O-tetra-decanoyl-phorbol 13-acetate (TPA) doubled the activity. This effect was counteracted by the protein kinase C inhibitor, polymyxin B, while thyroliberin-enhanced adenylate cyclase remained unaffected. In summary, we have described an adenylate cyclase with stimulatory (Rs) and inhibitory (Ri) receptors coupled to a calmodulin-sensitive holoenzyme through the Gs and Gi type of GTP-binding proteins. The ratio of the Gs to Gi is high. It appears that the GH4C1 cell adenylate cyclase is also activated by protein kinase C by interference with Gi. Apparently, thyroliberin activates the cyclase both directly through Gs and indirectly via protein kinase C stimulation. PMID- 2904369 TI - Unencapsulated Haemophilus influenzae--what kind of pathogen? AB - Haemophilus influenzae are small, gram-negative, rod-shaped bacteria. Because of their special growth requirements, they do not grow on usual blood agar media, but flourish on the mucosal membranes of the human respiratory tract where they adhere to the epithelial cells by fimbriae (a potential vaccine component). Nasopharyngeal carriage of Haemophilus influenzae is very common, and in healthy carriers the bacteria are usually unencapsulated. The outer membrane of Haemophilus influenzae contains lipopolysaccharide (of so called R form, without O antigen) and major outer membrane proteins. The lipopolysaccharide is a virulence determinant. An extracellular enzyme, IgA protease, is another potential virulence determinant. The outer membrane of Haemophilus influenzae is a rather ineffective barrier towards antibiotics, and thus the major determinants of antibacterial resistance in Haemophilus influenzae are plasmid-coded enzymes that inactivate the antibiotic, and changes in the target molecules. PMID- 2904370 TI - Incidence of aerobactin-positive Escherichia coli strains in patients with symptomatic urinary tract infection. AB - A total of 323 Escherichia coli strains from children with primary acute non obstructive pyelonephritis (n = 144) or cystitis (n = 56) and from adults with acute non-obstructive pyelonephritis (n = 66) or cystitis (n = 57) were examined for presence of the aerobactin-mediated iron uptake system and expression of P fimbriae. Overall, pyelonephritogenic Escherichia coli strains were significantly more often aerobactin-positive (72%) than cystitis strains (42%) (p less than 0.001). Seventy-three percent of the isolates from children with acute pyelonephritis were aerobactin-positive compared to 54% of the cystitis strains (p less than 0.05). Pyelonephritogenic Escherichia coli strains from adults were also significantly more often aerobactin-positive (70%) than cystitis strains (30%) (p less than 0.001). The cystitis strains from children were more often aerobactin-positive than cystitis strains from adult patients (p less than 0.05). There was a significant correlation between presence of the aerobactin-mediated iron uptake system and expression of P-fimbriae in all strains (p less than 0.001). PMID- 2904371 TI - Pharmacokinetics of a new sublingual formulation of temazepam. AB - The pharmacokinetics of a new 10 mg sublingual tablet formulation of temazepam and those of a currently marketed 10 mg oral capsule formulation were evaluated in a group of ten healthy volunteers. No significant differences were observed between the two formulations with respect to any of the pharmacokinetic parameters assessed. Lethargy and somnolence were reported on both capsule and tablet by several subjects at a time which corresponded with the maximum concentration of drug in plasma. The data indicate that the sublingual tablet and orally administered capsule have a similar pharmacokinetic and pharmacodynamic profile. PMID- 2904372 TI - Bovine non-pigmented and pigmented ciliary epithelial cells in culture: comparison of catalase, superoxide dismutase and glutathione peroxidase activities. AB - Non-pigmented epithelial (NPE) cells and pigmented epithelial (PE) cells were dissociated from bovine ciliary processes by brief digestion with pronase and grown in a culture medium containing high fetal bovine serum for at least 25 generations. Both types of cells grown to confluence showed the presence of intermediate junctions with associated tonofilaments. PE cells were distinguished from NPE cells by pigmentation during the early passages. Gamma-glutamyl transpeptidase activity was associated almost exclusively with NPE cells and proved to be a useful enzymatic marker to distinguish NPE from PE. A comparison was made between NPE and PE cells as to the levels of enzymes involved in the detoxification of active oxygen species. Catalase, Se-dependent glutathione peroxidase and superoxide dismutase activities were significantly higher in NPE than in PE cells. The results suggest that NPE cells play the major role in detoxification of active oxygen species during aqueous humor formation. PMID- 2904373 TI - Effects of selective dopamine-1 receptor activation on intraocular pressure in man. AB - The lack of specific agonists and antagonists has, until recently, precluded investigation of a role for dopamine receptors in the control of intraocular pressure. In the present study, we have examined the effects of fenoldopam, a novel selective dopamine1 (DA1) receptor agonist, on intraocular pressure, in eight healthy human volunteers. Fenoldopam, infused intravenously at 0.5 micrograms kg-1 min-1, increased intraocular pressure from 14.6 +/- 0.9 to 17.6 +/- 1.4 mmHg (P less than 0.05) while a control saline infusion had no effect. Pupil diameter and blood pressure did not change. In the same subjects, i.v. norepinephrine or angiotensin II both increased intraocular pressure--from 13.8 +/- 1.4- to 17.6 +/- 1.4 mmHg and from 13.4 +/- 1.3- to 17.5 +/- 1.7 mmHg respectively (P less than 0.05), and mean arterial pressure by about 20 mmHg. These data suggest that: (1) DA1 receptor activation can modulate intraocular pressure; (2) the intraocular pressure effects of the DA1 receptor agonist, fenoldopam, are independent of changes in systemic blood pressure, in contrast to those of norepinephrine or angiotensin II where intraocular and systemic blood pressures increase in parallel; (3) the ability of a DA1 receptor antagonist to lower intraocular pressure merits investigation. PMID- 2904374 TI - Cellular and molecular correlates of aging in the nervous system. AB - Three characteristic features of aging in the nervous system are reviewed: deficits in the regulation of nerve-cell calcium levels, increased leakage of synaptic transmitters and changes in neuronal arborization. In hippocampal cells and motor nerve terminals, the rate of calcium clearance from the immediate vicinity of the membrane decreases with age. There is further evidence of decreased rates of transmembrane Ca2+ flux in synaptosomal preparations from aged animals. Stimulation-evoked transmitter release, which is calcium dependent, appears to increase at some neuromuscular junctions during aging; in contrast, high-K+-induced release in brain tissue appears to decline. A much more consistent age-related increase in "basal" transmitter efflux, under nonstimulated conditions, has been observed in both the peripheral and the central nervous system. This may be related to increased nerve-terminal arborization, which occurs in actively used muscles during aging. Likewise, dendritic branching becomes more extensive with moderate age; at advanced age, though, branching decreases. Furthermore, motor nerve terminal branching also decreases with age in muscles subject to disuse. This variability among morphologic features during aging illustrates the need to standardize ages and preparations when comparing these types of data. PMID- 2904375 TI - Pharmacologic consequences of the vascular permeability of chromaffin cell transplants in CNS pain modulatory regions. AB - The transplantation of peripheral neural tissue into the CNS has been shown to alter blood-brain barrier (BBB) permeability to intravascularly injected proteins such as horseradish peroxidase. The pharmacological consequences of such BBB alterations following the transplantation of adrenal medullary tissue, isolated bovine chromaffin cell suspensions, or PC12 cell suspensions into the pain modulatory regions of the periaqueductal gray (PAG) or subarachnoid space of the lumbar spinal cord were studied using agents that normally do or do not readily pass the BBB. The injection of nicotine in animals with adrenal medullary or chromaffin cell transplants produces potent analgesia, most likely due to the stimulated release of opioid peptides and catecholamines from the transplanted cells. This analgesia could be blocked by nicotinic antagonist mecamylamine, which normally passes the BBB, but not by nicotinic antagonist hexamethonium, which normally does not readily pass the BBB. Furthermore, quaternary nicotinic agonists tetramethylammonium and 1,1-dimethyl-phenyl-piperazinium had no effect on pain sensitivity in animals with adrenal medullary implants. The Met enkephalin peptide analog, D-Ala-Met-enkephalinamide, which normally does not alter pain sensitivity when injected systemically due to limited penetration to the CNS, produced analgesia in animals with adrenal medullary, bovine chromaffin cell, and PC12 cell implants in the PAG, but not in control gelfoam-implanted animals. This analgesia, as well as analgesia induced by nicotine, was completely blocked by naloxone pretreatment, but not by naloxone methobromide, a quaternary derivative of naloxone that does not normally pass the BBB.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2904376 TI - Kynurenic acid and AP5 distinguish between NMDA receptor agonists. AB - Quantitative analysis of responses to amino acids in mouse cortical slices has indicated that the antagonists kynurenate and 2-amino-5-phosphonopentanoic acid distinguish between ibotenate and both N-methyl-D-aspartate (NMDA) and quinolinate. This result is consistent with the existence of NMDA-receptor subtypes. PMID- 2904377 TI - Opioids and cytosolic calcium in rat anterior pituitary: dynorphin preparation showed LHRH-like action due to contamination. AB - The effect of dynorphin A-(1-13) (Dyn A-(1-13] and other opioids on the cytosolic free calcium concentration [(Ca2+]i) in rat anterior pituitary cells was examined using the fluorescent indicator fura-2. A commercial synthetic Dyn A-(1-13) preparation elevated [Ca2+]i. Results, which were obtained with receptor antagonists, and in LHRH receptor radioligand binding studies as well as by HPLC combined with LHRH radioimmunoassay, strongly suggest that this effect of the dynorphin preparation was due to contamination with a LHRH-like compound. Dyn A (1-13), purified by HPLC, as well as Dyn A-(2-13), [Leu5]enkephalin, beta endorphin, morphine, or U50,488H had no effect on [Ca2+]i. LHRH caused a rapid increase in [Ca2+]i by about 50 nM which was blocked by the LHRH antagonist, [D pGlu1,D-Phe2,D-Trp3,6] LHRH. PMID- 2904378 TI - Azelastine inhibits bronchial hyperreactivity to acetylcholine in guinea pigs. AB - Contractile responses to acetylcholine were measured using isolated tracheae obtained from actively sensitized guinea pigs 0.5, 1, 5, 20, 24, 48 and 72 h after antigen challenge. Tracheal contractions to acetylcholine and to histamine were significantly increased 20 h but not 0.5, 1, 5, 24, 48 and 72 h after antigen challenge indicating bronchial hyperreactivity. When animals were pretreated with azelastine and then exposed to antigen challenge, concentration response curve to acetylcholine did not differ from that obtained in control (non challenged) tracheae. It is likely that azelastine is able to inhibit bronchial hyperresponsiveness to chemical mediators of bronchial asthma. PMID- 2904379 TI - Eosinophilic spleen colonies are produced in rat-marrow-transplanted but not in murine-marrow-transplanted mice. AB - Differential counts of about 5000 splenic clusters and colonies developing in whole-body-irradiated mice and rats were made, using semi-serial histological sections prepared 9 to 12 d after transplantation with bone marrow haemopoietic cells. The investigated mouse and rat spleens were from syngeneically, allogeneically, or xenogeneically transplanted recipients. Splenic eosinophil clusters were always found when rat eosinophil-producing progenitors were present in the inoculum, whereas murine inocula failed to produce splenic eosinophilic clusters even in the syngeneic mouse. The limiting factor in the production of splenic eosinophilic clusters was the appropriate donor progenitor/committed stem cell itself. Changes in the percentages of eosinophil clusters with the number of injected cells and with increased doses of irradiation, as well as formation of rat eosinophil colonies in mice, as against mainly clusters in rats, themselves show that regulatory mechanisms of the recipients also play a role. These regulatory mechanisms cannot be attributed to the splenic microenvironment. PMID- 2904380 TI - Heterogeneous expression of glutamine synthetase mRNA in rat liver parenchyma revealed by in situ hybridization and Northern blot analysis of RNA from periportal and perivenous hepatocytes. AB - Using radiolabeled specific cDNA glutamine synthetase mRNA could be detected by in situ hybridization exclusively within those few perivenous hepatocytes which stained immunocytochemically for glutamine synthetase. This localization of glutamine synthetase mRNA was recently reported by Moorman et al. [(1988) J. Histochem. Cytochem. 36, 751-755]. Biotinylated cDNA was not suitable for mRNA detection because of a very high background staining under the conditions of in situ hybridization. Dot blot and Northern blot analysis of RNA isolated from periportal and perivenous subfractions of hepatocytes also demonstrated the exclusive perivenous localization of two hybridizable glutamine synthetase mRNAs of length 2.8 and 1.6 kilobases. These results indicate that the unique heterogeneity of glutamine synthetase in rat liver parenchyma is controlled at the pretranslational level. PMID- 2904381 TI - The amyloid percursor protein of Alzheimer disease is expressed as a 130 kDa polypeptide in various cultured cell types. AB - The vascular and parenchymal amyloid deposits in Alzheimer disease (AD), normal aging and Down syndrome are mainly composed of a 4 kDa polypeptide (A4), which derives from a larger precursor protein (APP). There is evidence that APP is a transmembrane glycoprotein present in most tissues, but the characteristics of APP in intact cells are not yet known. In order to investigate this issue, we examined the immunoreactivity of fibroblasts of human and nonhuman cell lines with antisera raised to synthetic peptides corresponding to A4 and to two other domains of the APP. All three antisera recognized a 130 kDa polypeptide (APP-130) in immunoblots from all cell lines. In fibroblasts, an additional polypeptide of 228 kDa (APP-228) was recognized by the antiserum to A4. In immunoblots of two dimensional gels, APP-130 showed a pI of 6.2, while APP-228 failed to focus in the pH range of 4.7-7.0. Sequential extractions of cells with buffer and with Triton X-100 indicate that APP-130 is extractable with nonionic detergents at high ionic strength, whereas 228 kDa APP is a cystolic component. Immunofluorescence staining is consistent with an intracellular perinuclear and plasma membrane localization. It is concluded that APP-130 and APP-228 are two forms of the APP which result from extensive posttranslational modifications of a smaller original gene product. It is likely that APP undergoes similar posttranslational modifications in different cell types. PMID- 2904382 TI - [Neurochemical mechanisms of regulation in cataleptiform states in animals]. AB - Influence of serotonin- and GABA-ergic systems on cataleptic responses to electrical stimulation of the medial parabrachial nucleus, cuneiform nucleus, median and magnus raphe nuclei, was investigated in chronic experiments on rats. The brainstem structures seem to form a morphofunctional inhibitory system participating in catalepsy. PMID- 2904383 TI - Interaction of F1-ATPase and its inhibitor peptide. Effect of pH. AB - 1. The inhibition of F1-ATPase by its natural peptide inhibitor is mixed non competitive with two pH optimum values (5.5 and 8.2). 2. A two-step model for the interaction is suggested in which two enzyme conformations would exhibit different affinities for the peptide. 3. At low pH, interaction would be favoured. At high pH, a conformation (not susceptible to inhibition) changes into another (susceptible to inhibition) through the hydrolytic reaction stimulation, due to high pH. PMID- 2904384 TI - Interaction of F1-ATPase and its inhibitor peptide. Effect of dinitrophenol, nucleotides and anions. AB - 1. ATPase natural inhibitor interacted in a mixed non-competitive manner with compounds affecting hydrolytic activity. 2. Ka's for DNP, HCO3- and free ATP, and Ki's for SCN- and ADP became smaller as inhibitor peptide concentration increased, reflecting an increase in affinity of F1-ATPase for these compounds induced by the peptide. 3. Activators increased the peptide inhibitory effect, whereas inhibitors decreased it. 4. A two-step model for the peptide-enzyme interaction is suggested in which ATP hydrolysis is a key factor. PMID- 2904385 TI - The beta-subunit of the bovine mitochondrial F1 ATPase specifically binds the amino terminal domain of parathyroid hormone. AB - A protein which specifically binds the amino terminal domain of parathyroid hormone (PTH) on nitrocellulose blots of polyacrylamide gels was fragmented with cyanogen bromide (CNBr), and two fragments were sequenced through 20 residues. The sequence obtained was 100% homologous with the beta-subunit of bovine F1 mitochondrial ATPase. Purified F1 ATPase from bovine heart and Escherichia coli were obtained and the binding of PTH examined on the blots. The beta-subunit of the bovine enzyme bound PTH specifically through its amino terminal domain. However, both the alpha- and beta-subunit of the E. coli enzyme were found to bind the hormone. This binding was also specific for the amino terminal domain of the hormone. The subcellular distribution of the PTH-binding protein from bovine kidney was also examined further. While the mitochondria and plasma membrane appear to possess similar PTH-binding capability, submitochondrial particles enriched in F1 ATPase were also enriched in PTH-binding activity. PMID- 2904386 TI - Transforming growth factor-beta: multiple effects on cell differentiation and extracellular matrices. PMID- 2904387 TI - Murine glutamine synthetase: cloning, developmental regulation, and glucocorticoid inducibility. AB - We have cloned the murine glutamine synthetase (GS) gene and measured GS enzyme activity and mRNA in five tissues (retina, brain, liver, kidney, and skeletal muscle) during perinatal development. Retinal GS enzyme activity increases 200 fold between Day 1 and Day 21 and is accompanied by an increase in the level of GS mRNA; developmental regulation in other tissues is much less dramatic. Based on Southern blotting analysis, a single GS gene gives rise to the tissue-specific patterns of GS mRNA expression. The increase in murine retinal GS observed during perinatal development is similar in magnitude to that observed in the chicken retina just prior to hatching. In the embryonic chicken retina, glucocorticoid hormones mediate a large increase in the level of GS mRNA. However, although glucocorticoids induce a 12-fold increase in GS mRNA in murine skeletal muscle, expression of the retinal enzyme and mRNA is only modestly glucocorticoid inducible in the mouse. Therefore, despite the hormonal responsiveness of the murine GS gene, it is not likely that glucocorticoids are important physiological modulators of the developmental rise in murine retinal GS. PMID- 2904388 TI - Changes in myosin and C-protein isoforms proceed independently of the conversion to singly innervated neuromuscular junctions in developing pectoral muscle. AB - Changes in contractile protein expression during myogenesis are usually categorized as developmentally programmed or neuronally dependent. Studies on aneurogenic chick embryos indicated that the neuronally dependent phase begins at about Embryonic Day 15, immediately prior to the fetal transition in myosin and C protein expression. The prime candidate for the neuronal event that induces the fetal transition is the conversion to the adult form of singly innervated neuromuscular junctions (NMJs), which occurs contemporaneously with the fetal transition. Using curare to inhibit the conversion to focal innervation, we find that the fetal transition proceeds unimpaired, demonstrating that there is no causal link between the fetal transition and the conversion to focal innervation. Furthermore, because the doses of curare used inhibit motor activity by more than 80%, the fetal transition can occur in the absence of normal levels of motor activity. These observations show that the fetal transition in ovo is not induced by either a specific change in innervation or use. Rather, the dependence on innervation seems to be a consequence of the need for muscle activity to prevent atrophy, and the fetal transition appears to have characteristics more like the preprogrammed contractile protein transitions that precede it. PMID- 2904389 TI - Membrane voltage and neurotransmitter regulation of neuronal growth cone motility. AB - The neurotransmitters serotonin and dopamine inhibit growth cone motility and neurite elongation of specific identified neurons of the pond snail Helisoma. Similarly, experimentally evoked action potentials inhibit motility of these growth cones. Here we explore the possibility that the motility- and elongation inhibiting actions of serotonin and dopamine derive from the electrophysiological responses of the respective neurons. Evidence of three types in support of this hypothesis is presented: (1) Only those identified neurons for which motility is inhibited by serotonin or dopamine respond to the transmitter with sustained electrical excitation. (2) The magnitude of the electrical excitation response correlates with the degree of inhibition of growth cone motility. (3) The injection of hyperpolarizing current enables motility to continue as in the absence of transmitters. We conclude that membrane voltage is an important level of control of growth cone motility, at which neurotransmitters exert a regulatory influence. PMID- 2904390 TI - Peptidergic innervation of the adrenocorticotropic hormone (ACTH)- and growth hormone (GH)-producing cells in the pars distalis of the sea bass (Dicentrarchus labrax). AB - Due to its unique organization, the teleost pituitary is an ideal model in which to investigate the relationship of the nervous system with the pituitary endocrine cells. A light microscope immunocytochemical study of the sea bass pituitary revealed six different neuropeptides in nerve fibers which projected into the pituitary neurohypophysis and bordered the adenohypophysial cells. Double staining showed separate nerve fibers immunoreactive for corticotropin releasing factor (CRF), vasotocin (VT), somatostatin (SRIF), growth hormone releasing factor (GRF), and neurotensin (NT) in the vicinity of the adrenocorticotropic hormone-releasing cells (ACTH-cells) in the rostral pars distalis (PD). In the proximal PD cholecystokinin (CCK)-, SRIF-, GRF-, and VT immunoreactive fibers penetrated between the growth hormone-releasing cells (GH cells). These results suggest a possible role for CCK, GRF, SRIF, and VT in the modulation of GH-cell activity, while the synthesis and/or secretion of the ACTH cells might be affected by the release of VT, CRF, SRIF, GRF, and NT. PMID- 2904391 TI - Somatostatin-related and glucagon-related peptides with unusual structural features from the European eel (Anguilla anguilla). AB - Peptides derived from prosomatostatins I and II and from two distinct proglucagons have been isolated from the pancreas of a teleost fish, the European eel (Anguilla anguilla). The product of prosomatostatin I processing, somatostatin-14, is identical to mammalian somatostatin-14. A 25-amino-acid residue peptide (Ser-Val-Asp-Asn-Gln5-Gln-Gly-Arg-Glu-Arg10-Lys-Ala-Gly-Cys- Lys15-Asn-Phe-Tyr- Trp-Lys20-Gly-Pro-Thr-Ser-Cys25) is derived from prosomatostatin II. Compared with the corresponding peptides from other teleost fish, the eel somatostatin-25 contains the unusual substitution Pro for Phe at position 22. This peptide was also isolated in a form containing a hydroxylsyl residue at position 20. A 29-amino-acid-residue eel glucagon contains four substitutions relative to human glucagon Asn for Ser8, Glu for Asp15, Thr for Ser16, and Ser for Thr29). In common with mammalian and avian glucagons but unlike most other fish glucagons, the eel peptide possesses a glutamine residue at position 3. A peptide derived from a second proglucagon comprises 36 amino acid residues. A 7-residue C-terminal extension to the glucagon sequence shows structural similarity to the corresponding extension in ratfish (Hydrolagus colliei) glucagon and mammalian oxyntomodulin. PMID- 2904392 TI - Use of colonic eicosanoid concentrations as predictors of relapse in ulcerative colitis: double blind placebo controlled study on sulphasalazine maintenance treatment. AB - To establish whether concentrations of eicosanoids determined by equilibrium in vivo dialysis of faeces and equilibrium in vivo dialysis of rectum might predict a relapse in ulcerative colitis, 23 patients with completely inactive disease, maintained on sulphasalazine, stopped treatment and entered a prospective study. Concentrations of prostaglandin E2 were determined by radioimmunoassay on purified faecal and rectal dialysates at entry, at two weeks, and at two, six, and 12 months. If the above concentrations exceeded control concentrations (0.5 ng/ml and 1.0 ng/ml in faecal and rectal fluid, respectively) at any study day, the patient was allocated at random to double blind treatment with sulphasalazine 2 g/day, or placebo for six months. A relapse, defined as recurrence of symptoms accompanied by endoscopic inflammation occurred in none of six and in four of five patients allocated to sulphasalazine and placebo, respectively (p less than 0.05). In no case a normal rectal prostaglandin E2 concentration was associated with a relapse in the short term, but only two of 12 patients observed passively remained in remission. In retrospect, leukotriene B4 was a less sensitive predictor of relapse than prostaglandin E2. We conclude that raised concentrations of prostaglandin E2 in rectal dialysis fluid identify patients with a substantial risk of relapse. PMID- 2904393 TI - Gastrin cell function in familial multiple endocrine neoplasia type I. AB - Recent studies have suggested that patients with multiple endocrine neoplasia type I (MEN I) may have abnormal serum gastrin secretion in the absence of gastrin producing tumours. G-(gastrin) cell function by three provocation tests in 20 patients with hyperparathyroidism from six MEN I-families were studied: each patient was an obligate carrier of the MEN I-gene. The serum gastrin response to secretin was used to identify the presence of gastrinoma, that to a test meal of G-cell hyperfunction of the antral and/or duodenal mucosa, and that to bombesin to differentiate antral from duodenal G-cell hyperfunction. Seven patients had basal hypergastrinaemia and hyperchlorhydria. These patients had increased serum gastrin responses to secretin (p less than 0.01) and to bombesin (p less than 0.02), but normal postprandial responses. In the 13 normogastrinaemic patients the responses to the three stimuli were normal. In families with MEN-I gastrinoma is the only endocrine disorder accounting for abnormal gastrin secretion. G-cell function is normal in obligate carriers of the MEN I-gene. PMID- 2904394 TI - Twenty four hour intragastric acidity and plasma gastrin concentration in healthy volunteers taking nizatidine 150 mg, nizatidine 300 mg, ranitidine 300 mg, or placebo at 21:00 h. AB - Nine healthy volunteers were studied on the seventh day of dosing at 21:00 h with nizatidine 150 mg (N 150), nizatidine 300 mg (N 300), ranitidine 300 mg (R 300), or placebo, given in a predetermined random order. The double-blind 24 hour studies, using the Royal Free Hospital standard protocol, simultaneously measured intragastric acidity and plasma gastrin concentration. Compared with placebo, subjects responded to dosing with each H2-antagonist by a significant decrease of 24 hour intragastric acidity (N 150-45%; N 300-49% R 300-56%; p less than 0.01) and a significant rise of plasma gastrin concentration (N 150 + 20%; N 300 + 27%; R 300 + 58%; p less than 0.01). All three drug regimens caused similar significant decreases of nocturnal acidity (N 150-72%; N 300-79%; R 300-85%; p less than 0.01) and increases of nocturnal plasma gastrin concentration (N 150 + 41%; N300 + 52%; R 300 + 80%; p less than 0.01). Dosing with ranitidine 300 mg at 21:00 h also caused a simultaneous significant decrease of morning acidity (-32%; p less than 0.05) with a significant increase of plasma gastrin concentration (+36%; p less than 0.05), but the antisecretory effects of nizatidine 150 or 300 mg at 21:00 h were only observed during the night, with no effect during the morning. No drug regimen had any effect on acidity or plasma gastrin in the afternoon or early evening. PMID- 2904395 TI - Somatostatin on intravariceal pressure. PMID- 2904396 TI - [New momentum in cardiovascular therapy. Further development of ACE inhibitors: from captopril to lisinopril]. PMID- 2904397 TI - [Cardioprotection through ACE inhibition. Satellite symposium of the 12th scientific meeting of the International Society of Hypertension. 26 May 1988, Kyoto, Japan]. PMID- 2904398 TI - Sympatho-endocrine and metabolic responses to exercise under post-ganglionic blockade in rats. AB - The purpose of this study was to further document the role of locally released norepinephrine (NE) in the control of metabolic and endocrine responses to exercise in rats. Post-ganglionic blockade with bretylium (20 mg.kg-1, i.v.) reduced NE release from sympathetic nerve endings and triggered a compensatory increase in epinephrine (E) release from the adrenal medulla, as reflected by plasma NE and E concentrations at rest and exercise (E/NE ratio = 2.92 +/- 0.53 and 2.48 +/- 0.51 vs 0.62 +/- 0.15 and 1.48 +/- 0.18 in control rats; mean +/- SE). Following bretylium administration a reduction in running time to exhaustion (28 m.min-1, 8% slope: 33 +/- 2 min vs 74 +/- 10 min) was associated with 1) a faster decrease in blood glucose concentration (3.58 +/- 0.80 mM vs 8.09 +/- 0.38 mM in control rats exercised for 33 min); and 2) an increased glycogen store utilization in fast-twitch muscles (superficial vastus lateralis and gastrocnemius lateralis). Glycogen utilization was not modified in soleus muscle and in the liver. Taken together these results suggest that post-ganglionic blockade increased carbohydrate store and peripheral blood glucose utilization. This could reflect an impairment in fat mobilization and utilization which might be secondary to a reduction of NE release in the adipose tissue and/or in the endocrine pancreas. PMID- 2904399 TI - Human mitochondrial DNA types in Finland. AB - Variation in mitochondrial DNA (mtDNA) in a sample of 110 Finns was analyzed with six restriction enzymes, AvaII, BamHI, HaeII, HindII, HpaI, and MspI, by using total blood cell DNA probed with mouse mtDNA. Two new enzyme morphs were observed, one for HaeII and one for HindII. Double-digestion experiments indicated that the BamHI morphs 2 and 3 result from base changes leading to AvaII morphs 3 and 9, respectively. Of the ten different mtDNA types observed, defined by restriction fragment patterns, seven have been previously described in Caucasoid populations. The three new "Finnish" mtDNA types can be derived from Caucasoid lineages by single restriction site changes. The results were used to reconstruct a phylogenetic tree for Caucasoid mtDNA types defined by the enzymes used. The frequencies of mtDNA types were used to compute genetic distances between Finns, Italians, and Israeli Jews. The frequencies of both enzyme morphs and mtDNA types show that the Finnish population is highly homogeneous. PMID- 2904400 TI - The gene for X-linked progressive mixed deafness with perilymphatic gusher during stapes surgery (DFN3) is linked to PGK. AB - A linkage analysis has been performed in a large Dutch kindred with progressive mixed deafness with perilymphatic gusher during stapes surgery (DFN3) using a panel of X-chromosomal RFLPs. Tight linkage (zmax = 3.07 at 0 = theta = 0.00) was demonstrated with the locus for phosphoglycerate kinase (PGK), which is located at Xq13. Tight linkage was excluded for DXS9 (probe RC8) and DXS41 (probe 99.6) on Xp and for blood clotting factor 9 (FIX) on distal Xq. Deafness is one of the predominant clinical features in males with deletions of the Xq21 band. Our results suggest that this association may be due to involvement of the DFN3 gene. PMID- 2904401 TI - Use of restriction fragment length polymorphic probes in the analysis of Down's syndrome trisomy. AB - Restriction fragment length polymorphic probes are being used more frequently in the molecular analysis of Down's syndrome and in the origin of nondisjunction in the syndrome. The type of information gained from RFLPs overlaps but differs from the information from cytogenetic heteromorphisms. From the allele frequencies of commonly available probes we have derived the expected frequencies of all matings in the population. Each mating has been defined and partitioned to show the genotypes and phenotypes expected, with numerical values based on studies with heteromorphisms. From this we show how the various phenotypes can be used to calculate the origin of nondisjunctions and their expected frequencies. Further, an alternative method is outlined for mapping the distance between a probe and its centromere based on the distortion, caused by crossing-over, of the expected 1st to 2nd division nondisjunction ratio. Finally, we discuss prospects for various uses of probes in the analysis of Down's syndrome. PMID- 2904402 TI - Dissociation between mental retardation and fragile site expression in a family with fragile X-linked mental retardation. AB - We report an extended family in which two brothers with a fragile X chromosome are mentally retarded while a third brother with the fragile site is both phenotypically and mentally normal. The study of six probes detecting restriction fragment length polymorphisms on either sides of the fragile site Xq27 confirmed that the fragile X regions inherited by these three brothers were identical from DXS102 to the telomere. These data highlight the heterogeneity of the fragile X syndrome, which is discussed in the framework of the different hypotheses previously proposed. PMID- 2904403 TI - A highly conserved sequence on the short arm of chromosome 7 detects multiple polymorphisms. AB - We have isolated a human DNA fragment (laboratory acronym G98) that detects related sequences in mammals, chicken and Drosophila DNAs. This sequence has been mapped to human chromosome 7 p14-p15 by in situ hybridization. Probe G98 recognizes an insertion-deletion type polymorphism, with allelic frequencies of about 0.5, which can be detected with at least six different restriction enzymes. A second polymorphism, which can be detected in human DNA digested with TaqI, is in non-complete linkage disequilibrium with the first polymorphism. About 70% of the individuals analysed have been found to be heterozygous at this locus. PMID- 2904404 TI - Lesch-Nyhan syndrome: molecular investigation of three French Canadian families using a hypoxanthine-guanine phosphoribosyltransferase cDNA probe. AB - Using human hypoxanthine-guanine phosphoribosyltransferase (HPRT) cDNA and an anonymous probe 36B-2, we examined the segregation of restriction fragment length polymorphism (RFLP) alleles with the Lesch-Nyhan phenotype in three affected families. Two families were informative. Five carriers of the mutation in one family and two potential carriers in the second were heterozygous for either one or both polymorphisms allowing for prenatal diagnosis. Southern blot patterns in patients from these three families indicated the absence of major structural alterations in the defective gene. Northern analysis using HPRT cDNA as a probe revealed no hybridizing RNA in one patient, whereas normal size mRNA was expressed at a very low level in the second and at a level comparable to normal in the third. These data are consistent with heterogeneity of Lesch-Nyhan genetic lesions resulting from point mutations or small DNA deletions or rearrangements, which may affect transcription, stability, or integrity of the HPRT message. PMID- 2904405 TI - Cystic fibrosis: typing 89 German families with linked DNA probes. AB - Three hundred and ninety-two subjects from 89 German families were typed for restriction fragment length polymorphisms (RFLPs) detected by the probes pmetH, pmetD, pJ3.11, KM19, and XV2c known to be tightly linked to the cystic fibrosis (CF) gene. The analysis of the predictive value of this typing in individual CF families indicates that the combined use of these probes provides a powerful diagnostic system for both carrier detection and prenatal diagnosis. In 45 families the complete haplotype including all RFLPs was available. Of them 41 (91.1%) were fully informative and 4 were partly informative. PMID- 2904406 TI - DNA haplotypes of the human apoprotein B gene in coronary atherosclerosis. AB - Haplotypes of the apoprotein B gene, localised to chromosome 2, were identified using restriction fragment length polymorphisms (RFLPs) for the enzymes XbaI and EcoRI. Four haplotypes were identified at this locus, X1R1 (H1), X1R2 (H2), X2R1 (H3) and X2R2 (H4); where the X1 and X2 alleles were characterised by gene related fragments of 5.0 and 8.6 kb respectively and the R1 and R2 alleles by fragments of 13.0 and 11.0 kb respectively. Although the polymorphic sites are less than 10 kb apart, they were found to be in linkage equilibrium. The value of the disequilibrium parameter (D) was 0.0042, approximately 7.5% of the theoretical maximum (Dmax = 0.054). No disease association could be demonstrated between either apoB RFLP, or haplotype, and coronary athersclerosis in our population from south-east England. This was in accordance with a study of apoB RFLPs for a population from the West Coast of the United States, but in contrast to a study of an East-Coast population. There are no previous data for the association between apoB haplotypes and coronary atherosclerosis. PMID- 2904408 TI - A new method for FXIIIA genetic variants determination using isoelectric focusing in 1 M urea. Evidence for three structural gene loci, FXIIIA1, FXIIIA2, and FXIIIA3. AB - A new method for separating genetic variants of the A subunit of human coagulation factor XIII using ultrathin layer polyacrylamide gel isoelectric focusing in 1 M urea followed by immunoblotting is described. The pattern obtained by this method differs from that reported previously: Three sets of unrelated band patterns are observed and can be explained by the existence of two additional gene loci, designated FXIIIA2 and FXIIIA3, besides the previously reported FXIIIA locus, now renamed FXIIIA1. The FXIIIA2 locus is polymorphic and shows three commonly occurring phenotypes, FXIIIA2 1, FXIIIA2 2-I, and FXIIIA2 2. These are determined by two common alleles, FXIIIA2*1 and FXIIIA2*2, with respective frequencies of 0.7965 and 0.2035 in the Japanese population. The studied population conforms to a Hardy-Weinberg equilibrium, and family data confirmed autosomal codominant transmission. The FXIIIA3 locus is monomorphic. PMID- 2904407 TI - Linkage studies in X-linked Alport's syndrome. AB - Four kindreds segregating for Alport's syndrome (ASLN) compatible with a X-linked inheritance were studied for linkage with polymorphic markers of the human X chromosome. No recombinant was observed between the ASLN locus and the DXS101 and DXS94 loci, the maximum lod scores were z = 3.93 and 3.50 respectively. Linkage data between the ASLN locus and the other genetic markers used in the present study are in keeping with the assignment of the mutation to the proximal Xq arm. PMID- 2904409 TI - Examination of the differential characteristics of amplifier and contrasuppressor T cells. AB - Vicia villosa lectin-adherent Lyt-1+ spleen cells, obtained 4 days after immunization with an optimally immunogenic dose (0.5 micrograms) of Type III pneumococcal polysaccharide (SSS-III), increased the magnitude of the antibody response of mice to SSS-III upon transfer to recipients also immunized with the same antigen; however, the ability to demonstrate such enhancement depended greatly upon when such cells were transferred relative to immunization of recipients. Lectin-adherent cells augmented the antibody response of athymic nude (nu/nu) mice to SSS-III, and abrogated the expression - but not the induction - of low-dose immunological paralysis, a form of unresponsiveness mediated by suppressor T cells. These findings are consistent with effects usually attributed to the action of amplifier, rather than contrasuppressor, T cells. PMID- 2904410 TI - On the convulsant action of DMCM and Ro 5-4864 in mice. PMID- 2904411 TI - Effect of hormones on the development of various brush border enzymes across crypt-villus axis in rat intestine. PMID- 2904412 TI - A simple & rapid Dot-ELISA dipstick technique for detection of antibodies to Entamoeba histolytica in amoebic liver abscess. PMID- 2904413 TI - Reversal of metabolic & electrocardiographic changes induced by Indian red scorpion (Buthus tamulus) venom by administration of insulin, alpha blocker & sodium bicarbonate. PMID- 2904414 TI - DNA restriction fragment length polymorphism analysis of human bronchogenic carcinoma. AB - DNA restriction fragment length polymorphism (RFLP) analysis has been successfully applied both to evaluate possible human susceptibility factors as well as to identify genes involved in malignant transformation of human cells. In this report we review previous applications of RFLP analysis to evaluation of human malignancies and discuss our RFLP studies of human bronchogenic carcinoma, which are in progress. Preliminary results of our analysis of the RFLP associated with the cHa ras variable tandem repeat (VTR) indicate that rare alleles of this VTR are more frequent in patients with bronchogenic carcinoma than in controls. PMID- 2904415 TI - Opioids. PMID- 2904416 TI - Modern approaches to the diagnosis and management of anovulation. PMID- 2904417 TI - Treatment of hydrosalpinx using a single incision eversion procedure. AB - Between January 1981 and December 1986, 93 patients underwent microsurgery for hydrosalpinx. A single incision was used to open the hydrosalpinx. The edges were rolled back and imbricated with 7-0 and 8-0 polyglactin sutures. A 94% patency rate was obtained, with an overall pregnancy rate of 53%. The full-term pregnancy rate was 40% in tubes with normal-appearing fimbria, and 28% in tubes with absent fimbria. The presence or absence of fimbria appeared to have the best predictive value for successful pregnancy following microsurgical treatment of distal tubal obstruction. PMID- 2904418 TI - Microscopic evidence of silent inflammation in grossly normal fallopian tubes with ectopic pregnancy. AB - A normal laparoscopic examination of the pelvis in an infertile patient is usually considered sufficient evidence of normal tubal function. Twelve of 27 tubal ectopic pregnancies which occurred over a 4-year period in patients attending an infertility clinic were in patients with a previously "normal" laparoscopy. In eight patients, salpingectomy was performed, and the whole tube was available for examination by a single pathologist. The eight fallopian tubes, thoroughly examined histologically, all had evidence of ongoing, low-grade salpingitis or postinflammatory endosalpingeal disorganization in areas away from the ectopic pregnancy. These findings suggest that laparoscopy does not exclude significant microscopic tubal disease in at least some women with an apparently normal pelvis, and that this may be a cause of ectopic pregnancy and perhaps "idiopathic" infertility. PMID- 2904419 TI - Endometrial biopsies during treatment with subcutaneous pulsatile gonadotropin releasing hormone and luteal-phase human chorionic gonadotropin. AB - A high incidence of luteal phase defect (LPD) has been reported using subcutaneous pulsatile gonadotropin-releasing hormone for induction of ovulation. We reviewed all patients treated with the combination of subcutaneous pulsatile gonadotropin-releasing hormone during the follicular phase and human chorionic gonadotropin during the luteal phase (GnRH-hCG) who underwent endometrial biopsy during a treatment cycle. All of these patients had biopsy-proven LPD which persisted despite traditional therapy with progesterone vaginal suppositories and/or clomiphene citrate. The mean number of biopsies out of phase per patient prior to GnRH-hCG treatment was 2.8 +/- 0.2 (+/- SEM). When treated with GnRH hCG, 15/16 patients (94%) showed a normal endometrial biopsy. The probability of this result occurring by chance alone allowing for a 50% treatment independent correction rate is less than .001. These results show that the combination of subcutaneous pulsatile gonadotropin-releasing hormone and luteal-phase human chorionic gonadotropin can result in normal endometrial maturation in a high percentage of cycles when administered as described. It appears to be an effective alternative to traditional treatment modalities for luteal phase defect should one be needed. PMID- 2904420 TI - Effect of the mode of clomiphene citrate administration on ovarian response in an in vitro fertilization program. AB - To increase oocyte recovery for in vitro fertilization, superovulation treatment combining clomiphene citrate (CC) and human menopausal gonadotropin (hMG) is often used. However, CC may also have undesirable effects, e.g., on the endometrium, and therefore, high CC doses should be avoided. We studied the effects of three different modes of CC administration on ovarian estradiol (E2) responses and additive follicular diameters developed during 42 stimulated cycles. The treatments were (1) 150 mg CC on cycle days 5 to 9, (2) 50 mg CC on cycle days 3 to 7, or (3) 50 mg CC on cycle days 5 to 9. On the seventh cycle day, 300 IU hMG was given to all patients and this was continued for 3 to 4 days in decreasing doses depending on the ovarian responses, followed by daily E2 analyses and ultrasound measurements. The peripheral E2 concentrations during the different modes of CC administration were identical on cycle days 7 to 12. In addition, the additive follicular diameters on the day of hCG administration and the total hMG doses used did not differ significantly between the three CC administration groups. Thus, a dose of 50 mg CC daily seems to be large enough to lead to maximal ovarian response in combination with hMG, and a treatment period of cycle days 3 to 7 appears to be suitable. In this way the interval between the cessation of CC and embryo transfer is maximal, and possible deleterious effects on the endometrium are minimized. PMID- 2904421 TI - Proximal tubal occlusion: microsurgery versus IVF--a review. AB - The success of IVF has established it as a viable alternative to microsurgery in the treatment of infertility associated with certain types of tubal occlusion. The authors have recently reported on the success rates of microsurgery versus IVF in cases of distal tubal occlusion. The present study summarizes the results reported in the world literature for microsurgery in cases of proximal tubal occlusion secondary to surgical sterilization, previous infection, or endometriosis, and compares them with the results reported for IVF. Based on what has been published to date, it appears that microsurgical tubocornual anastomosis remains the procedure of choice for proximal tubal occlusion. PMID- 2904422 TI - A pelvic scoring system for infertility surgery. AB - A pelvic scoring system for infertility surgery was devised in which pelvic pathology is assessed for comparative and prognostic purposes. Pelvic pathology was divided into three areas: adhesions (ADH), salpingitis (SPG), and tubal occlusion (TOC). The extent of pathology was scored as mild (1), moderate (2), severe (3), or extensive (4). The maximum scores for adhesions, salpingitis, and tubal occlusion were 48, 24, and 28, respectively--various weightings were applied and subareas accounted for. The pelvic score (PLV#) was simply the sum of the adhesions (ADH#), salpingitis (SPG#), and tubal occlusion (TOC#) scores. The stage of pelvic pathology was arbitrarily assigned as stage 0, I, II, III, and IV with PVL#'s of 0, 1-25, 26-50, 51-75, and 76-100, respectively. A close correlation (r = .960-.990) of PLV# was noted between different observers using this system. Poorer reproductive potential was observed in the patients with higher scores and stages. This scoring system properly reflects clinical experience and can be relied on for patient counseling via prediction of prognosis. This system can be utilized to compare objectively the results of infertility surgery between surgeons as well as among institutions. PMID- 2904423 TI - Fertility studies in sickle cell disease: semen analysis in adult male patients. AB - Semen analysis was done on 50 subjects (25 patients with sickle cell anemia and 25 control subjects with normal hemoglobin genotype). The ejaculate volume, sperm motility, sperm density, and normal sperm morphology were significantly reduced in the patients when compared with the control subjects. A significant increase was also observed in the percentage of spermatids and in abnormal spermatozoa with amorphous and tapered heads in the patients' semen. These findings clearly show that there are definite abnormalities associated with semen in sickle cell anemia. Furthermore, they suggest that in addition to testicular dysfunction, there may be abnormalities in the accessory sex organs, such as the seminal vesicles and the prostate gland, particularly in view of the marked decrease in ejaculate volume of the patients. PMID- 2904424 TI - Failure of hysteroscopic insemination of the fallopian tube in synchronized cycles. AB - The study consisted of a randomized, controlled trial of synchronized hysteroscopic insemination of the fallopian tube (SHIFT), in which selected infertile couples underwent hormonal delay of menstruation, ovulation induction, and insemination of a selected motile sperm population into the tubal isthmus above the utero-tubal junction. Of 40 couples recruited, only 2 became pregnant, both during a nonsynchronized control cycle. No conceptions were reported in either the 72 SHIFT or 73 non-SHIFT synchronized cycles. Hysteroscopic insemination was found to be a relatively easy procedure with a low rate of technical failure. There was low morbidity with no major clinical complications. However, 57% of tracked synchronized cycles showed a failed response to the follicular stimulation protocol; and 91% showed failure of follicular rupture greater than or equal to 52 hours after hCG induction. These failures of the ovulation synchronization/induction regimen were probably due to the use of medroxyprogesterone acetate for cycle synchronization, and should not preclude further evaluation of the technique of hysteroscopic insemination. PMID- 2904425 TI - Reproductive endocrine function in gossypol-treated male rats. AB - The mode and sites of antifertility action of gossypol were explored in Long Evans rats for the purpose of clarifying effects on endocrine function. Mature male rats were treated every five days with gossypol acetic acid (10 mg/kg of body weight, given subcutaneously). Although no conspicuous loss in sperm motility and breeding performance occurred with this dosing regimen, even after prolonged treatment, a statistically significant reduction in serum testosterone (T) and decreases in accessory organ weights were observed after only 3 weeks. Testosterone propionate (500 micrograms daily, subcutaneously) administered concurrently with gossypol to gonadectomized rats prevented the decrease in accessory organ weight, indicating that gossypol probably affects these organs indirectly by altering circulating androgen levels. In another experiment, serum T was measured in gossypol-treated (10 mg/kg/day for 100 days, subcutaneously) and control rats before and after a single challenge dose of 20 IU of hCG. Even though prechallenge serum T levels were suppressed in gossypol-treated rats, postchallenge levels were similar to controls, indicating the absence of significant impairment in interstitial cell response to gonadotropin stimulation. There was also no evidence that the anterior pituitary gland was directly affected by gossypol treatment. PMID- 2904426 TI - Adhesion re-formation in the rabbit uterine horn model: I. Reduction with carboxymethylcellulose. AB - Adhesion re-formation frequently complicates the performance of adhesiolysis in reproductive pelvic surgery. To assess the ability of carboxymethylcellulose (CMC) to reduce adhesion re-formation, a rabbit uterine horn model was employed. Adhesions were created at laparotomy by scraping a 5-cm segment of each uterine horn. This injury reproducibly creates adhesions. Two weeks later, repeat laparotomy was performed, at which time all adhesions were lysed by sharp dissection. Animals were then randomly assigned to the control or CMC (20 mL of 2% solution) group. Necropsy was performed 2 weeks later. At both the second operative procedure and the time of necropsy, adhesions were graded in a blind fashion for severity and tenacity. There was no difference in adhesion score in the control and CMC-treated rabbits at the time of adhesiolysis. Subsequently, at the time of necropsy, the mean adhesion reformation score in the control group was 3.96 (median = 4.0). In contrast, adhesion re-formation in the CMC-treated group was significantly less (mean score = 2.15; median = 2.0; sign test, P less than .01). In summary, CMC significantly reduced adhesion re-formation in the rabbit uterine horn model. The mechanism by which CMC was able to reduce adhesion reformation is uncertain, but may be related to "hydroflotation" or "siliconizing" effects. PMID- 2904427 TI - Cellular and tissue distribution of MRK20 murine monoclonal antibody-defined 85 kDa protein in adriamycin-resistant cancer cell lines. AB - A murine monoclonal antibody (MAb) specific to adriamycin-resistant K-562 (K 562/ADM) cells, MRK20, was found to react strongly with an 85-kDa protein present in K-562/ADM and adriamycin-resistant ovarian cancer (2780AD) cells. This protein was present at only very low levels in parental cells (K-562 and A2780), methotrexate-resistant K-562 cells (K-562/MTX3, K-562/MTX4 and K-562/MTX5) and cisplatin-resistant ovarian cells (KFr). Immunoelectron microscopically, the protein was found to be located on the cell membrane of K-562/ADM and 2780AD cells. Furthermore, the presence of the protein in various cell lines, normal tissues and surgical materials from patients given no anti-cancer agents was examined by immunocytochemistry and flow cytometry. MRK20 reacted with granulocytes, monocytes and endothelial cells in various tissues, but did not react with tissue macrophages. This 85-kDa protein recognized by MRK20 seems to be the second multidrug-resistance gene-encoded product appearing in adriamycin resistant cancer cells, following the characterization of 170-180-kDa glycoprotein, and may be important for elucidating the multidrug-resistance mechanism relevant to adrimycin and Vinca alkaloids. PMID- 2904428 TI - Psychosocial and medical histories of stimulant-treated children. PMID- 2904429 TI - Emerging treatment options in the alcohol withdrawal syndrome. AB - Severe alcohol withdrawal has a mortality rate of 5% to 10%. Uncontrolled bouts may sensitize the patient, making future episodes more frequent and severe. Thus, aggressive treatment that produces rapid control of alcohol withdrawal is essential. The author briefly discusses some of the neuropharmacological aspects of alcohol's actions and alcohol withdrawal. Drug treatment options are also considered. Benzodiazepines offer the highest margin of safety. Lorazepam is an excellent first choice because of its intermediate half-life, absence of active metabolites, and high bioavailability that can be achieved with a number of routes of administration. Combination therapy with clonidine, beta-adrenergic blocking agents, and haloperidol is becoming increasingly attractive because it results in decreased sedation, better control of delirium, less respiratory depression, and improved outcome. The availability of shorter half-life, rapid acting drugs like esmolol and midazolam, administered by continuous infusion, makes dose titration more precise in the critically ill patient. PMID- 2904430 TI - Rapid tranquilization: antipsychotics or benzodiazepines? AB - With the advent of rapid tranquilization (RT), psychiatrists were able to intervene quickly and effectively with psychotic, agitated, and potentially assaultive patients. As RT often obviated the need for physical restraints, it became a mainstay in emergency psychiatry. While studies have repeatedly demonstrated the safety and efficacy of antipsychotic medication to achieve RT, there has been some concern about potential untoward side effects, such as neuroleptic malignant syndrome, tardive dyskinesia, and extrapyramidal symptoms. As a result, many investigators have begun exploring alternatives to the use of antipsychotics for RT. Benzodiazepines are among the classes of drugs most often discussed. The author reviews the current literature on both antipsychotics and benzodiazepines and summarizes the results of several extensive reviews of RT that have appeared in the past few years. The author also critically examines the literature on the use of benzodiazepines for RT, with emphasis on lorazepam and clonazepam. Finally, the author proposes tentative guidelines for RT and directions for future clinical research. PMID- 2904431 TI - Somatostatin-immunoreactive concentrations in human saliva and in the submandibular salivary glands of the rat. Possible sexual dependence in the human. AB - Many biologically active polypeptides have been detected either in the submandibular salivary glands (SSG) of the rat, and in the saliva of rats and humans. The present work has investigated the case of somatostatin (SRIF), since salivary data concerning the presence of this peptide are scarce and contradictory. In a group of healthy volunteers, SRIF-immunoreactivity (SRIF-IR) was tested in samples of mixed saliva. Not all the subjects revealed presence of SRIF-IR in saliva. For men, 5 out of 9 were positive (x = 26.40 +/- 10.03 pg/ml), whereas for women only one out of 10 was positive (x = 96.40 pg/ml). SRIF-IR was also determined in male rat submandibular glands from control animals (26.1 +/- 6.3 pg/mg protein, n = 18) and from animals injected one hour before with an alpha 1-adrenergic secretagogue, phenylephrine (27.9 +/- 7.1 pg/mg protein, n = 6). The results show that SRIF-IR is not constantly present in human saliva obtained from a young population, and that its presence apparently seems to differ between the sexes. On the other hand, the fact that SRIF-IR, unlike other peptides, is not modified when the animals are injected with phenylephrine, may simply indicate that the control mechanism of SRIF-IR release is not the same as that affecting other salivary peptides. Further studies must be carried out in order to elucidate the origin and role of salivary SRIF-IR. PMID- 2904432 TI - Resonance Raman studies on the blue-green-colored bovine adrenal tyrosine 3 monooxygenase (tyrosine hydroxylase). Evidence that the feedback inhibitors adrenaline and noradrenaline are coordinated to iron. AB - Tyrosine 3-monooxygenase (tyrosine hydroxylase) is a non-heme iron, tetrahydropterin-dependent enzyme which catalyzes the rate-limiting step in the biosynthesis of catecholamines. The highly purified bovine adrenal enzyme contains an unusual blue-green chromophore with lambda max at around 700 nm (epsilon = 1.3 (mM subunit enzyme)-1 cm-1). On excitation at 605.2 nm, resonance enhanced Raman vibrations are observed at 454, 494, 527, 604, 635, 835, 1130, 1271, 1320, 1426, and 1476 cm-1. The excitation profiles of the modes of 1276 and 1476 cm-1 (from 488 to 620 nm) follow the contour of the 700 nm absorption band. The vibrations observed strongly indicate the presence of a bidentate catecholamine-Fe(III) complex in the enzyme as isolated which gives rise to the characteristic charge-transfer transitions. This is further supported by the release of 0.11 +/- 0.04 mol of noradrenaline and 0.25 +/- 0.06 mol of adrenaline per mol of enzyme subunit on denaturation of the enzyme. The energies of the catecholate to Fe(III) charge-transfer transitions indicate a mixture of histidines and carboxylate(s) coordinated to the iron center in tyrosine hydroxylase. At neutral pH, the enzymatic activity was inhibited more than 50% by 10 microM dopamine, noradrenaline, and adrenaline. The high affinity of the catecholamines to the nonphosphorylated form of tyrosine hydroxylase may have significance in vivo since catecholamines are potent feedback inhibitors of the enzyme. PMID- 2904433 TI - ATP synthase complex from beef heart mitochondria. Role of the thiol group of the 25-kDa subunit of Fo in the coupling mechanism between Fo and F1. AB - In order to assess the role of thiol groups in the Fo part of the ATP synthase in the coupling mechanism of ATP synthase, we have treated isolated Fo, extracted from beef heart Complex V with urea, with thiol reagents, primarily with diazenedicarboxylic acid bis-(dimethylamide) (diamide) but also with Cd2+ and N ethylmaleimide. FoF1 ATP synthase was reconstituted by adding isolated F1 and the oligomycin-sensitivity-conferring-protein (OSCP) to Fo. The efficiency of reconstitution was assessed by determining the sensitivity to oligomycin of the ATP hydrolytic activity of the reconstituted enzyme. Contrary to Cd2+, incubation of diamide with Fo, before the addition of F1 and OSCP, induced a severe loss of oligomycin sensitivity, due to an inhibited binding of F1 to Fo. This effect was reversed by dithiothreitol. Conversely, if F1 and OSCP were added to Fo before diamide, no effect could be detected. These results show that F1 (and/or OSCP) protects Fo thiols from diamide and are substantiated by the finding that the oligomycin sensitivity of ATP hydrolysis activity of isolated Complex V was also unaltered by diamide. Gel electrophoresis of FoF1 ATP synthase, reconstituted with diamide-treated Fo, revealed that the loss of oligomycin sensitivity was directly correlated with diminution of band Fo 1 (or subunit b). Concomitantly a band appeared of approximately twice the molecular weight of subunit Fo 1. As this protein contains only 1 cysteine residue (Walker, J. E., Runswick, M. J., and Poulter, L. (1987) J. Mol. Biol. 197, 89-100), the effect of diamide is attributed to the formation of a disulfide bridge between two of these subunits. These results offer further evidence for the proposal, based on aminoacid sequence and structural analysis, that subunit Fo 1 of mammalian Fo is involved in the binding with F1 (Walker et al. (1987]. N-Ethylmaleimide affects oligomycin sensitivity to a lesser extent than diamide, suggesting that the mode of action of these reagents (and the structural changes induced in Fo) is different. PMID- 2904434 TI - The fluorescein isothiocyanate-binding site of the plasma-membrane H+-ATPase of Neurospora crassa. AB - The mammalian (Na+,K+), Ca2+-, and (H+,K+)-ATPases contain a well-characterized lysine residue that reacts with fluorescein 5'-isothiocyanate (FITC); enzymatic activity is protected by ATP, suggesting that the residue is located in or near the nucleotide-binding domain. In this study, the plasma-membrane H+-ATPase of Neurospora crassa is also shown to be sensitive to FITC. The reaction occurs with pseudo first-order kinetics, has a pKa of 8.0, and is stimulated by Mg2+. Enzymatic activity is protected by MgADP with a Kd of 0.2-0.3 mM, close to the Ki with which MgADP serves as a competitive inhibitor of ATP hydrolysis. A tryptic peptide labeled with FITC in the absence, but not in the presence, of MgADP has been isolated and sequenced. The FITC-sensitive residue is Lys474, located in a region that exhibits significant homology with the mammalian cation-transporting ATPases. PMID- 2904435 TI - Catalytic site occupancy during ATP hydrolysis by MF1-ATPase. Evidence for alternating high affinity sites during steady-state turnover. AB - The mechanism of ATP hydrolysis by the solubilized mitochondrial ATPase (MF1) has been studied under conditions where catalytic turnover occurs at one site, uni site catalysis (obtained when enzyme is in excess of substrate), or at two sites, bi-site catalysis (obtained when substrate is in excess of enzyme). Pulse-chase experiments support the conclusion that the sites which participate in bi-site catalysis are the same as those which participate in uni-site catalysis. Upon addition of ATP in molar excess to MF1, label that was bound under uni-site conditions dissociates at a rate equal to the rate of bi-site catalysis. Similarly, when medium ATP is removed, label that was bound under bi-site conditions dissociates at a rate equal to the rate of uni-site catalysis. Evidence that a high affinity catalytic site equivalent to the one observed under uni-site conditions participates as an intermediate in bi-site catalysis includes the demonstration of full occupancy of a catalytically competent site during steady-state turnover at nanomolar concentrations of ATP. Improved measurements of the interaction of ADP at a high affinity catalytic site have lead to the revision of several of the rate constants that define uni-site catalysis. The rate constant for unpromoted dissociation of ADP is equal to that for Pi (4 X 10( 3) s-1). The rate of binding ADP at a high affinity chaseable site (Kd = 1 nM) is equal to the rate of binding ATP (4 X 10(6) M-1 s-1). The rate of catalysis obtained when substrate binding at one site promotes product release from an adjacent site (bi-site catalysis) is up to 100,000-fold faster than unpromoted product release (uni-site catalysis). PMID- 2904436 TI - cDNA sequence and predicted primary structure of the gamma subunit from the ATP synthase from Chlamydomonas reinhardtii. AB - The 1701-base nucleotide sequence (not including the poly(A) tail) of a cDNA for the gamma subunit of the ATP synthase from Chlamydomonas reinhardtii was determined. A start translation sequence, 23 bases in from the 5' end, initiates an 1074-base-long open reading frame. The sequence of the first 21 amino acids at the amino-terminal end of the mature gamma subunit from C. reinhardtii was determined and compared to the deduced amino acid sequence of the open reading frame. From this it was determined that the mature protein contains 323 amino acids, with the first 35 amino acids probably being part of the transit peptide. The length of the mature protein is the same as that for the mature gamma subunit from spinach, for which only a few of the amino acids of the transit peptide are known. The similarity of the two mature proteins at the nucleotide level is 56% while at the amino acid level it is 77%. In addition, the 3 cysteines, which in spinach are involved in the energy-linked catalytic functions of the ATP synthase, are conserved in the predicted amino acid sequence for the gamma subunit from C. reinhardtii. In contrast, the mature C. reinhardtii gamma subunit contains 3 additional cysteine residues not found in the spinach gamma subunit. PMID- 2904437 TI - A second transport ATPase gene in Saccharomyces cerevisiae. AB - A second transport ATPase gene from Saccharomyces cerevisiae has been identified by hybridization to a PMA1 probe and sequenced. The gene called PMA2 encodes a polypeptide of Mr = 102,157, which, with the exception of the 144 amino-terminal residues, is highly homologous to the structural gene PMA1 for the H+-ATPase. It is localized on the chromosome XVI at 16.7 centimorgan from gal4 and is not essential for haploid growth. Comparison between the upstream, noncoding DNA regions of PMA1 and PMA2 indicates that the two genes are controlled differently. The extensive amino acid sequence homology with the fungal H+-ATPases described so far indicates that the PMA2-encoded protein is also able to function as a H+ pump. This is supported by the observation that in pma1 mutants with reduced plasma membrane ATPase activity, disruption of the PMA2 gene confers the ability to grow under alkaline pH conditions. Slower development of diploids is also observed on normal minimal medium after bilateral disruption of PMA2 in the two parents. PMID- 2904438 TI - High resolution deuterium NMR studies of bacterial metabolism. AB - High resolution deuterium NMR spectra were obtained from suspensions of five bacterial strains: Escherichia coli, Clostridium perfringens, Klebsiella pneumoniae, Proteus mirabilis, and Staphylococcus aureus. Deuterium-labeled D glucose at C-1, C-2, and C-6 was used to monitor dynamically anaerobic metabolism. The flux of glucose through the various bacterial metabolic pathways could be determined by following the disappearance of glucose and the appearance of the major end products in the 2H NMR spectrum. The presence of both labeled and unlabeled metabolites could be detected using 1H NMR spectroscopy since the proton resonances in the labeled species are shifted upfield due to an isotopic chemical shift effect. The 1H-1H scalar coupling observed in both the 2H and 1H NMR spectra was used to assign definitively the resonances of labeled species. An increase in the intensity of natural abundance deuterium signal of water can be used to monitor pathways in which a deuteron is lost from the labeled metabolite. The steps in which label loss can occur are outlined, and the influence these processes have on the ability of 2H NMR spectroscopy to monitor metabolism are assessed. PMID- 2904439 TI - Cytoplasmic pH regulation in macrophages by an ATP-dependent and N,N' dicyclohexylcarbodiimide-sensitive mechanism. Possible involvement of a plasma membrane proton pump. AB - Cytoplasmic pH (pHi) regulation was studied in thioglycolate-elicited murine macrophages using fluorescent probes. Acid-loaded macrophages regained normal pHi by extrusion of H+ equivalents across the plasma membrane. A fraction of this recovery was due to Na+/H+ exchange, as evidenced by its partial Na+ dependence and amiloride sensitivity. The residual, Na+-independent pHi recovery (approximately 50% of the total) persisted in the nominal absence of HCO3- and was insensitive to disulfonic stilbenes, ruling out mediation by anion exchange. In contrast, intracellular alkalinization and H+ extrusion from the cells were inhibited by N-ethylmaleimide, by N,N'-dicyclohexylcarbodiimide or by prior depletion of intracellular ATP. These observations are consistent with the existence of a H+-pumping ATPase in the plasma membrane of macrophages. The mechanism of activation of the ATP-dependent H+ extrusion process was also investigated. In other systems, Ca2+ mobilization has been suggested to signal an exocytic insertion of H+ pumps into the plasma membrane. Acid loading of macrophages was accompanied by an elevation of the cytosolic Ca2+ concentration ([Ca2+]i), measured using indo-1. These results are consistent with a role for Ca2+ mobilization in the activation of H+ extrusion. PMID- 2904440 TI - Directed mutagenesis of the strongly conserved aspartate 242 in the beta-subunit of Escherichia coli proton-ATPase. AB - Oligonucleotide-directed mutagenesis was used to substitute Asn or Val for residue Asp-242 in the beta-subunit of Escherichia coli F1-ATPase. Asp-242 is strongly conserved in beta-subunits of F1-ATPase enzymes, in a region of sequence which shows homology with numerous nucleotide-binding proteins. By analogy with adenylate kinase (Fry, D.C., Kuby, S.A., and Mildvan, A.S. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 907-911), beta-Asp-242 of F1-ATPase might participate in catalysis through electrostatic effects on the substrate Mg2+ or through hydrogen bonding to the substrate(s); an acid-base catalytic role is also plausible. The substitutions Asn and Val were chosen to affect the charge, hydrogen-bonding ability, and hydrophobicity of residue beta-Asp-242. Both mutations significantly impaired oxidative phosphorylation rates in vivo and membrane ATPase and ATP driven proton-pumping activities in vitro. Asn-242 was more detrimental than Val 242. Purified soluble mutant F1-ATPases had normal molecular size and subunit composition, and displayed 7% (beta-Asn-242) and 17% (beta-Val-242) of normal specific Mg-ATPase activity. The relative MgATPase activities of both mutant enzymes showed similar pH dependence to normal. Relative MgATPase and CaATPase activities of normal and mutant enzymes were compared at widely varied pMg and pCa. The mutations had little effect on KM MgATP, but KM CaATP was reduced. The data showed that the carboxyl side-chain of beta-Asp-242 is not involved in catalysis either as a general acid-base catalyst or through direct involvement in any protonation/deprotonation-linked mechanism, nor is it likely to be directly involved in liganding to substrate Mg2+ during the reaction. Specificity constants (kcat/KM) for MgATP and CaATP were reduced in both mutant enzymes, showing that the mutations destabilized interactions between the catalytic nucleotide-binding domain and the transition state. PMID- 2904441 TI - Complete kinetic and thermodynamic characterization of the unisite catalytic pathway of Escherichia coli F1-ATPase. Comparison with mitochondrial F1-ATPase and application to the study of mutant enzymes. AB - A complete analysis is presented of the component rate constants of the "unisite" reaction pathway in normal Escherichia coli F1-ATPase. Gibbs free energy profiles of the unisite reaction pathway were constructed for both normal E. coli F1 and bovine-heart mitochondrial F1, and comparison indicated that E. coli F1 is an ancestral form of the mitochondrial enzyme. Similar kinetic and thermodynamic analyses of the unisite reaction pathway were done for mutant beta-Asn-242 and beta-Val-242 E. coli F1-ATPases. Both mutations affected unisite binding and hydrolysis of MgATP but had little effect on release of products or binding of MgADP. It was apparent that a primary effect of the mutations was on the interaction between the catalytic nucleotide-binding domain and the substrate MgATP. The catalytic transition state [F1-ATP]++ was the most destabilized step in the reaction sequence. Measurements of delta delta G[F1.ATP]++ and linear free energy plots for the catalytic step were consistent with the view that, in normal enzyme, residue beta-Asp-242 accepts an H-bond from the transition-state substrate in order to facilitate catalysis. Both mutations impaired positive catalytic cooperativity. This was caused by energetic destabilization of the catalytic transition state and was an indirect effect, not a direct effect on signal transmission per se between catalytic nucleotide-binding domains on beta subunits. Therefore, impairment of unisite catalysis and of positive catalytic cooperativity appeared to be linked. This may provide a unifying explanation as to why a series of other, widely separated mis-sense mutations within the catalytic nucleotide-binding domain on F1-beta-subunit, which have been reported to affect unisite catalysis, also impair positive catalytic cooperativity. Linear free energy plots for the ATP-binding step of unisite catalysis demonstrated that beta-Asn-242 and beta-Val-242 mutant enzymes did not suffer any gross disruptive change in structure of the catalytic nucleotide-binding domain, reinforcing the view that impairment of catalysis was due to a localized effect. Such analyses confirmed that six other F1-beta-subunit mutants, previously generated and characterized in this laboratory and thought to have inhibitory side-chain substitutions in the catalytic nucleotide-binding domain, are also devoid of gross structural disruption. PMID- 2904442 TI - Lipopolysaccharides in a traditional pertussis vaccine. AB - Analysis of the lipopolysaccharide (LPS, endotoxin) in cell sonicates of four Danish vaccine strains of Bordetella pertussis (3803, 3825, 3843 and 3860) and of purified strain 3803 LPS in sodium dodecyl sulphate-polyacrylamide gel electrophoresis by silver staining, showed identical profiles. The LPS profile revealed a dominant, brownish LPS II band and a minor, faster-migrating, black stained LPS I band. However, the ratio of LPS I to LPS II in the preparation of purified LPS differed slightly from the cell sonicates. Using marker LPS, the molecular weights of LPS I and LPS II were estimated at 5.4 and 6.0 kD, respectively. Seven different lots of whole cell pertussis vaccine were assayed for LPS in the Limulus Amoebocyte Lysate test and were found to contain 0.9-2.8 micrograms LPS/ml. No significant difference in the content of LPS in similar dilutions of the individual strains was observed. In addition, the distribution of free and cell-bound LPS in four pertussis vaccines was investigated. Most of the LPS was found to exist as free LPS. During several months, the course of both LPS and pertussis toxin (Pt) release in freshly killed B. pertussis preparations was followed. In the first few weeks, 35-50% of the LPS was released and after 5 6 months of storage 60-80% had been released. In contrast, less than 10% of the biologically active pertussis toxin was released during the experimental period. The possibility of producing a safer whole cell pertussis vaccine by reducing the amount of free LPS without reducing the protective value correspondingly is discussed. PMID- 2904443 TI - The isolated rat portal vein as a model for studying beta-adrenoreceptor agonists and antagonists. AB - 1. The isolated rat portal vein was employed for essaying beta-agonists and beta antagonists. beta-agonists elicit a log-dose dependent reduction of force of the spontaneous, rhythmic, myogenic contractions of the vein. The ID50 dose for isoprenaline was 8.40 +/- 0.04 SEM (negative log. of the molar concentration). Isoprenaline was the most potent of the beta-agonists. If given the value 100, then fenoterol is 75; salbutamol 10; terbutaline 6.75 and during alpha-blockade, adrenaline 28.80 and noradrenaline 0.27. The ratio of potency is thus ISOP greater than FENOT greater than ADR greater than SALB greater than TERB greater than NOR. This suggests that the predominant beta-receptors are beta 2. 2. The duration of effects was shortest for isoprenaline and largest for fenoterol and terbutaline. 3. With the highly potent, specific, competitive beta 2-blocker ICI 118551, a pA2 against isoprenaline of 9.30 (+/- SEM 0.03; C.L. 95% 9.22-9.38) was found. The pA2 against fenoterol, terbutaline, adrenaline and noradrenaline were included in these confidence-limits. With propranolol, a pA2 against isoprenaline of 8.82 (+/- SEM 0.02) was obtained. 4. The high pA2 found against non-selective (isoprenaline, adrenaline) and selective (fenoterol, terbutaline) beta 2-agonists is, as said, practically the same. This, together with the potency ratio ISOP greater than ADR greater than NOR, markedly suggest that the population of beta receptors in the smooth muscle of the rat portal vein is homogeneously beta 2. 5. The method is very useful to essay beta-agonists and beta-antagonists. As straight regression lines with very high correlation coefficients are obtained, the potency and efficacy of agonists may be relatively easily obtained. PMID- 2904444 TI - Alpha 1- and alpha 2-adrenoreceptor antagonists produce opposing mydriatic effects by a central action. AB - 1. In anaesthetized rats, intravenous administration of alpha 2-adrenoreceptor antagonists yohimbine (0.3-3.0 mg kg-1), idazoxan (0.03-0.3 mg kg-1) and raulwolscine (0.3-3.0 mg kg-1) produced a dose-related inhibition of sciatic nerve-(ScN) mediated reflex pupillary dilation (parasympatho-inhibition). The rank order of potency was idazoxan greater than yohimbine greater than rauwolscine. 2. Under similar experimental conditions, intravenous administration of alpha 1-adrenoreceptor antagonists prazosin (0.03-1.0 mg kg-1), phenoxybenzamine (0.3-3.0 mg kg-1) and corynanthine (0.03-1.0 mg kg-1) produced a dose-dependent potentiation of the reflex mydriasis with the potency order being prazosin greater than corynanthine greater than phenoxybenzamine. Intravenous yohimbine (1.5 mg kg-1) reversed the potentiation caused by the alpha 1 adrenoreceptor antagonists and blocked the reflex mydriasis. 3. Parasympatho inhibition and mydriasis elicited by hypothalamic stimulation was not affected by the alpha 2-adrenoreceptor antagonists yohimbine (0.3-3.0 mg kg-1), idazoxan (0.03-0.3 mg kg-1) or the alpha 1-adrenoreceptor antagonist prazosin (0.3-1.0 mg kg-1). 4. Microinjection of prazosin (3-30 ng) into the oculomotor nuclear complex (IIIn), produced a dose-related potentiation, whereas microinjection of yohimbine (0.3-3.0 micrograms) produced a dose-related blockade of reflex mydriasis. 5. The above findings support the hypothesis that ascending mechanisms (e.g. afferent ScN) produce inhibition of parasympathetic oculomotor tone to the iris by activation of central postsynaptic alpha 2-adrenoreceptors. Furthermore, these studies demonstrate that alpha 2-adrenoreceptor antagonists block and alpha 1-adrenoreceptor antagonists potentiate the reflex mydriasis. These actions appear to be localized within the pupilloconstrictor regions of the brain (oculomotor nuclear complex). PMID- 2904445 TI - A chimeric mitochondrial precursor protein with internal disulfide bridges blocks import of authentic precursors into mitochondria and allows quantitation of import sites. AB - Bovine pancreatic trypsin inhibitor (which contains three intramolecular disulfide bridges) was chemically coupled to the COOH terminus of a purified artificial mitochondrial precursor protein. When the resulting chimeric precursor was presented to energized isolated yeast mitochondria, its trypsin inhibitor moiety prevented the protein from completely entering the organelle; the protein remained stuck across both mitochondrial membranes, with its NH2 terminus in the matrix and its trypsin inhibitor moiety still exposed on the mitochondrial surface. The incompletely imported protein appeared to "jam" mitochondrial protein import sites since it blocked import of three authentic mitochondrial precursor proteins; it did not collapse the potential across the mitochondrial inner membrane. Quantification of the inhibition indicated that each isolated mitochondrial particle contains between 10(2) and 10(3) protein import sites. PMID- 2904447 TI - Retrovirus-mediated expression of preprosomatostatin: posttranslational processing, intracellular storage, and secretion in GH3 pituitary cells. AB - Somatostatin (SRIF) is a 14-amino acid peptide hormone that is synthesized as part of a larger precursor, preproSRIF, consisting of a signal peptide and a proregion of 80-90 amino acids. The mature hormone, which is located at the carboxyl terminus of the precursor, is preceded by a single pair of basic amino acids. We are studying preproSRIF to investigate intracellular sorting, proteolytic processing, and storage of peptide hormone precursors in the secretory pathway. We used a retroviral expression vector to achieve the high levels of precursor synthesis which are necessary for detailed characterization of processing intermediates and mature somatostatin. Recombinant retroviruses containing RNA transcripts encoding anglerfish preproSRIF I were used to infect rat pituitary GH3 cells which secrete growth hormone and prolactin, neither of which are substrates for endoproteolytic cleavage. In these cells preproSRIF was accurately processed to the mature hormone with an efficiency of approximately 75%. Of the newly synthesized mature SRIF, 55% was sorted into the regulated secretory pathway and released in response to the secretagogue 8-Br-cAMP. The remaining 45% of mature SRIF and residual unprocessed precursor was rapidly secreted. In contrast to SRIF, only 5% of newly synthesized endogenous growth hormone was stored intracellularly, whereas 95% was sorted to the constitutive pathway and secreted rapidly with kinetics identical to proSRIF. Our results show that proSRIF processing is not necessarily dependent on a specific protease found only in SRIF-producing cells and suggest that proteolytic cleavage is not restricted to cells that process endogenous hormones. Moreover, these results demonstrate that GH3 cells have the capacity to discriminate between endogenous and foreign hormones and target the foreign molecule significantly more efficiently to the regulated secretory pathway. PMID- 2904446 TI - Alphavirus RNA replicase is located on the cytoplasmic surface of endosomes and lysosomes. AB - Using morphological and cell biological techniques, we have shown that the RNA replicase of Semliki Forest and Sindbis virus (two closely related alphaviruses) is located in complex ribonucleoprotein structures associated with the cytoplasmic surface of modified secondary lysosomes and endosomes. These nucleoprotein complexes often form a bridge between the membrane of the endocytic vacuole and the rough endoplasmic reticulum where the synthesis of the structural proteins of these viruses occurs. The results suggest that these cytopathic vacuoles constitute sites not only for viral RNA synthesis, but also for translation of structural proteins, and for the assembly of nucleocapsids. PMID- 2904448 TI - Hierarchies of protein cross-linking in the extracellular matrix: involvement of an egg surface transglutaminase in early stages of fertilization envelope assembly. AB - The involvement of transglutaminase activity in fertilization envelope (FE) formation was investigated using eggs from the sea urchin, Strongylocentrotus purpuratus. Eggs fertilized in the presence of the transglutaminase inhibitors, putrescine and cadaverine, had disorganized and expanded FEs with inhibition of the characteristic I-T transition. The permeability of the FE was increased by these agents, as revealed by the loss of proteins from the perivitelline space and the appearance of ovoperoxidase activity in supernates from putrescine treated eggs. [3H]putrescine was incorporated into the FE during fertilization in a reaction catalyzed by an egg surface transglutaminase that could also use dimethylcasein as a substrate in vitelline layer-denuded eggs. Egg secretory products alone had no transglutaminase activity. The cell surface transglutaminase activity was transient and maximal within 4 min of activation. The enzyme was Ca2+ dependent and was inhibited by Zn2+. We conclude that sea urchin egg surface transglutaminase catalyzes an early step in a hierarchy of cross-linking events during FE assembly, one that occurs before ovoperoxidase mediated dityrosine formation (Foerder, C. A., and B. M. Shapiro. 1977. Proc. Natl. Acad. Sci. USA. 74:4214-4218). Thus it provides a graphic example of the physiological function of a cell surface transglutaminase. PMID- 2904449 TI - Cytoskeletal involvement in the sequential capping of rat thymocyte surface glycoproteins. AB - The independent capping of the three major rat thymocyte glycoproteins, the leucocyte-common (L-C) antigen, the leucocyte sialoglycoprotein (LSGP) and Thy-1, was investigated using specific monoclonal antibodies. The capping of each antigen did not require redistribution of the other major surface glycoproteins, and was accompanied by a partial co-capping of the cytoskeletal proteins fodrin and actin, but not of tubulin. A study of the ability of a cell that already possesses one glycoprotein cap to cap a second different glycoprotein showed that this was possible in all cases to varying degrees, the second cap always forming at the same position on the cell surface as the first. Colchicine failed to perturb this observed sequential capping polarity, indicating that microtubules did not direct this second capping event. PMID- 2904450 TI - L-428 nodular sclerosing Hodgkin's cell secretes a unique transforming growth factor-beta active at physiologic pH. AB - Nodular sclerosing Hodgkin's disease is characterized by dense collagen fibrosis. Although transforming growth factor-beta (TGF-beta) is an important bifunctional growth factor for fibroblasts and is stored and released by many cells, it requires acidification to pH 2.0-3.0 before it becomes a biologically active growth factor. We show here that the L-428 Hodgkin's cell releases a high molecular weight TGF that competes for the TGF-beta cell membrane receptor but not the TGF-alpha receptor. This growth factor is most active at physiologic pH and is 97% inactivated by acidification. Hodgkin's TGF is also inactivated by proteases and can be preserved by protease inhibitors. The Hodgkin's TGF can be separated from an autocrine growth factor using either column chromatography or electroelution from gels and is shown to have a molecular weight of approximately 350,000. Incubation of the Hodgkin's TGF in SDS releases a 25,000-D protein with reduced biological activity but which cross-reacts with anti-TGF-beta IgG. We propose that L-428 nodular sclerosing Hodgkin's disease fibrosis is mediated by a potent high molecular weight TGF-beta which, unlike TGF-beta characterized to date, is secreted in a form most active at physiologic pH. PMID- 2904451 TI - Localization of a proton-pumping ATPase in rat kidney. AB - The distribution of vacuolar H+ATPase in rat kidney was examined by immunocytochemistry using affinity-purified antibodies against the 31-, 56-, and 70-kD subunits of the bovine kidney proton pump. Proximal convoluted tubules were labeled over apical plasma membrane invaginations, and in the initial part of the thin descending limb, apical and basolateral plasma membranes were moderately stained. Thick ascending limbs and distal convoluted tubules were apically stained although the intensity was greater in the distal convoluted tubule. Collecting duct principal cells were virtually unlabeled, but intercalated cells had intense staining with an apical, basolateral or diffuse pattern in the cortex, and exclusively apical staining in the medulla. These results (a) show the presence of an H+ATPase in the apical plasma membrane of the proximal tubule that may contribute to H+ transport in this segment; (b) provide direct evidence that the intercalated cell contains most of the H+ATPase detectable in the collecting duct, supporting its proposed role in H+ transport; (c) demonstrate that subpopulations of cortical intercalated cells have opposite polarities of an H+ATPase, consistent with the presence of both proton- and bicarbonate-secreting cells; and (d) suggest a role for the H+ATPase in acid/base regulation or H+ transport in segments other than the collecting duct and the proximal tubule. PMID- 2904452 TI - Immunocytochemical demonstration of dynorphin(PH-8P)-like immunoreactive elements in the human hypothalamus. AB - PH-8P (dynorphin[1-8])-like immunoreactive neuronal perikarya, processes, and terminals located within the human hypothalamus were investigated by the avidin biotin peroxidase complex (ABC) immunocytochemical procedure. Immunopositive neurons were distributed throughout the hypothalamus. The distributional pattern was found to be similar to that in other mammalian species by the use of antisera against dynorphin. A large number of immunoreactive neuronal perikarya were detected in the supraoptic nucleus (SON) and the magnocellular portion of the paraventricular nucleus (PVN). Their processes appeared to project to the posterior pituitary via the internal layer of the median eminence and their distribution seemed to be less dense than in other mammalian species. PH-8P and vasopressin were colocalized in the neuronal perikarya in the human SON unlike the colocalization of these peptides in the rat SON and PVN. There were a few immunoreactive terminals in the external layer of the median eminence; their immunoreactive substances may be released into the portal veins to act on anterior pituitary cells. In addition, PH-8P-like immunoreactive neurons in the human hypothalamus may project to the extrahypothalamic area. PMID- 2904453 TI - Behavioral and anatomical correlates of immunologically induced rejection of nigral xenografts. AB - Cell suspensions derived from the ventral mesencephalon of CD-1 mice were unilaterally transplanted into the striatum of neonatal Sprague-Dawley rats that had been bilaterally dopamine depleted. Thirty-eight percent of the grafts survived. Tyrosine-hydroxylase-immunoreactive neurons within the transplant innervated the host striatum with a dense fiber plexus. The grafts appeared to exert some degree of functional control over motor behavior in that these animals made contralateral rotations in response to amphetamine and tail pinch. In order to provide additional evidence that the motor behavior is associated with the transplant itself, the graft was removed. This was achieved by using a mouse skin graft to provoke an immunological response against the transplanted neural tissue. The immunological response resulted in the specific loss of the transplant with little or no damage to the surrounding neural tissue. The amount of rotation observed after tail pinch and amphetamine injection was severely affected by neural graft rejection. The loss of turning was associated most directly with the loss of tyrosine hydroxylase immunoreactivity within the transplant rather than with the massive reduction of tyrosine-hydroxylase positive fibers in the ipsilateral host striatum. These data suggest that dopamine cells in mouse nigral grafts play an essential role in eliciting rotational behavior in neonatally dopamine depleted rats. They also show the value of skin grafting as a technique for specifically removing neural xenografts. PMID- 2904454 TI - Virus diarrhoea in hospital. PMID- 2904455 TI - Colonization priority among Staphylococcus aureus strains--correlation with phage type. AB - We have studied the distribution of phage-type patterns among strains of Staphylococcus aureus isolated from patients in a burns unit. From 51 patients the same phage-type was isolated from succeeding swabs during the observation period. In 20 patients new types were introduced, but the original strain remained. In 23 patients the first strain was replaced by one other strain, in eight patients two or more. Strains of type 95 seemed to have a high colonization priority, whereas strains of group III had a low one. In 1986 phage-typing was performed on two or more S. aureus strains from the same patient, in 4561 instances. Recurrence of strains of the same phage-type pattern was demonstrated in 70% of the patients when the first and the fourth sample were compared. The "newer epidemic" strains of phage-type 95 and of the 94,96 complex had the highest percentage of recurrence (more than 80%) when adjacent samples were compared, and 68-69% when the first and the fourth sample were compared. The good colonization capacity of these strains might be one of the explanations why they occur frequently today although they are resistant only to penicillin. PMID- 2904456 TI - A laboratory model for testing agents for hygienic hand disinfection: handwashing and chlorhexidine for the removal of klebsiella. AB - A model for the laboratory assessment of hygienic hand disinfection is described which closely reproduces handwashing in a ward setting. The model uses a clinically relevant test organism and takes into account the natural antibacterial action of the skin. It also provides a means of measuring any residual antibacterial action after hand disinfection. Using an epidemic multiply resistant strain of Klebsiella aerogenes K21, 0.5% chlorhexidine in iso-propyl alcohol yielded sterile post-disinfection finger washings more often than 4% chlorhexidine digluconate. Both preparations were more effective than soap and water, and with each residual action was demonstrable. The model is applicable to the laboratory evaluation of hygienic hand procedures and for agents of potential use in defined clinical settings. PMID- 2904457 TI - Screening for enteropathogenic Escherichia coli. AB - In an attempt to identify the prevalence of enteropathogenic Escherichia coli (EPEC) carriage and to minimize the chances of admitting a baby to the neonatal wards with unsuspected EPEC infection, 27,174 maternity patients admitted in labour and 4049 neonates admitted to the Special Care Baby Unit (SCBU) were screened for intestinal carriage of common EPEC serotypes. Two hundred and sixty five (1%) maternity patients were positive, of whom 8 (3%) had diarrhoea. Of the babies born to these mothers, 10 (3.8%) were infected with EPEC and in each the serotype was the same as the mother's. Nine neonates (0.2%) admitted to the SCBU were also found to be infected with EPEC. Seven of the 19 babies (37%) had diarrhoea. Symptomatic mothers or babies were nursed in isolation. During the 8 year period under study no incidents of cross-infection with EPEC occurred. PMID- 2904458 TI - The use of a monoclonal antibody serotyping system in the study of the epidemiology of Pseudomonas aeruginosa. AB - A monoclonal antibody method was used as a primary O serotyping method for 1084 isolates of Pseudomonas aeruginosa, using commercially available antibody reagents in slide agglutination tests with whole-cell antigen. Differences in distribution of serogroups were found between various hospitals in the district. Serotyping provided useful information in the investigation of suspected incidents of cross-infection. Colonization at multiple sites, or over periods of time, in a single patient usually involved only a single serogroup. PMID- 2904459 TI - Predictive value of surveillance skin and hub cultures in central venous catheters sepsis. AB - In a prospective study of septic complications of central venous catheters used for total parenteral nutrition, daily surveillance catheter hub cultures and twice weekly skin cultures at the catheter entry site were evaluated for their predictive value for catheter sepsis, i.e. bacteraemia with an identical species as that recovered from the catheter tip, or catheters which grew greater than or equal to 15 cfus by a semiquantitative method and/or greater than or equal to 10(3) cfus by a quantitative method. Of 142 catheters studied, 29 were identified to have catheter sepsis. For these the sensitivity of the surveillance hub culture was 34.5% and the sensitivity of the skin culture was 37.9%. When either the hub or the skin culture result was considered as an indication of catheter sepsis, the sensitivity increased to 79.3%. The positive and negative predictive value of the combined result was 44.2% and 93.3% respectively. This study suggests that simultaneous hub and skin cultures are required for a satisfactory surveillance. PMID- 2904460 TI - Urethral and prostatic colonization and infection in patients undergoing prostatectomy. AB - We conducted a prospective trial to identify organisms colonizing the urethra and prostate and their role in the aetiology of infection after prostatectomy. Twenty five patients were studied of whom six developed postoperative infection. The causative organisms were previously recovered from the urethra but not the prostate. There was a high rate of urethral colonization by streptococci (14/25) and a low incidence of prostatic colonization. We describe a novel method of sampling the prostate. PMID- 2904461 TI - A trial of mezlocillin versus cefuroxime with or without metronidazole for the prevention of wound sepsis after biliary and gastrointestinal surgery. AB - A randomized controlled trial was undertaken to compare the role of mezlocillin, as the sole prophylactic agent, with a combination of cefuroxime and metronidazole in patients undergoing biliary and gastrointestinal surgery. No difference in wound infection rates was seen in patients following appendicectomy, biliary or gastro-oesophageal surgery. A significantly higher wound infection rate was seen in patients undergoing colorectal surgery who received mezlocillin alone (30.2%) compared with those receiving cefuroxime and metronidazole (11.5%): this rate was similar to that of historical placebo controls in other units. The wound infections seen in patients receiving mezlocillin alone were polymicrobial involving organisms of faecal origin, including non-sporing anaerobes which were predominantly sensitive to mezlocillin. Infections due to Staphylococcus aureus, resistant to mezlocillin, were more frequent in patients receiving mezlocillin and usually secondary in nature. We conclude that mezlocillin may be an effective sole prophylactic agent in appendicectomy but not in colorectal surgery; the possible reasons for failure to adequately prevent infection, following colorectal surgery, are discussed. PMID- 2904462 TI - A prospective randomized trial to compare triple dose mezlocillin with triple dose cefuroxime plus metronidazole as prophylaxis in colorectal surgery. AB - The results of a prospective randomized clinical trial to compare three dose regimens of mezlocillin with cefuroxime plus metronidazole for prophylaxis in emergency and elective colorectal surgery are reported. Severe wound infection occurred in five patients (10%) receiving mezlocillin and in four patients (7%) receiving cefuroxime and metronidazole. There were two episodes of septicaemia, each in the mezlocillin group. The total number of surgically related infections was less with cefuroxime plus metronidazole (n = 10) compared with mezlocillin (n = 17), but this was not statistically significant (P greater than 0.1). PMID- 2904463 TI - Enterobius vermicularis infection in a children's ward. AB - Following the discovery that two patients on a children's orthopaedic ward were excreting Enterobius, all patients and staff on the ward were screened for the presence of pinworms. None of the staff was infected but 11 (55%) of 20 patients either had Enterobius ova on the anal margin or excreted worms following piperazine treatment. Epidemiological investigations indicated that this was unlikely to be a ward outbreak because four of the infected children had been on the ward for under 3 days, i.e., less than the prepatent period for Enterobius. Although none of the children was symptomatic, all children and staff on the ward were treated with piperazine. Faecal samples were collected from nine children and the majority of their worm load was shed within 32 h of starting therapy. Microscopic examination of the adult male worms showed that each patient was excreting both Enterobius vermicularis and E. gregorii. PMID- 2904464 TI - Simple peroperative antimicrobial chemoprophylaxis in elective neurosurgical operations. AB - From August 1981 to February 1982 postoperative infections due to different strains of penicillin-resistant Staphylococcus aureus occurred in 20 of 467 patients (4.3%) undergoing elective cranial and spinal operations. These infections were not attributable to defects in procedures or the theatre environment, therefore chemoprophylaxis was instituted. In the following 8 months, when patients were given penicillin G and sulphadiazine for 5 days commencing immediately postoperatively, S. aureus infections occurred in five of 579 patients (0.9%). In a subsequent randomized uncontrolled study, infections occurred in six of 265 patients receiving penicillin (2.3%), three of 270 receiving penicillin and sulphadiazine (1.1%) and one of 45 receiving erythromycin (2.2%) immediately postoperatively for 5 days. In a further study in which 587 patients received penicillin for 5 days commencing immediately preoperatively, infections due to S. aureus occurred in six (1.1%). Infections due to gram-negative organisms were seen in five (0.4%) of 1167 patients in the two uncontrolled studies. PMID- 2904465 TI - Efficacy of the antiseptic solution 'TCP' against Staphylococcus aureus and Pseudomonas aeruginosa. PMID- 2904466 TI - Spore tests for low temperature steam with formaldehyde sterilizers. PMID- 2904467 TI - A marker of personal hygiene? PMID- 2904468 TI - Pseudobacteriuria with Serratia marcescens. PMID- 2904469 TI - Two populations of methicillin- and gentamicin-resistant Staphylococcus aureus strains in a regional hospital in Hong Kong: epidemiology and plasmid profile studies. PMID- 2904470 TI - Interstrain restriction fragment length polymorphism of c-fos and c-src oncogene loci in spontaneously hypertensive and normotensive rats. AB - Interstrain restriction fragment length polymorphism was detected after Southern blot hybridization of spontaneously hypertensive (SHR) and control (WKY) rat DNA digested by Bam HI restrictase with a v-fos probe. The SHR genome was characterized by an additional minor band of 4.0 kb. Other restriction fragment length polymorphism was revealed in the c-src locus by Eco RI, Hind III and Pst I restrictases. The major characteristic bands were 1.6 kb (SHR) and 2.4 kb (WKY) after Eco RI restriction; 3.4 kb (SHR) and 4.1 kb (WKY) after Hind III restriction and 4.0 kb (SHR) and 4.6 kb (WKY) after Pst I restriction. This restriction fragment length polymorphism can be used as Mendelian traits in linkage studies on the distribution of blood pressure and other quantitative physiological traits in (SHR x WKY)F2 hybrids. PMID- 2904471 TI - Expression of the beta-subunit of the human leukocyte adherence receptor depends upon cell type and stage of differentiation. AB - Using a cDNA clone for the beta-subunit of the receptor on human leukocytes that mediates cellular adherence (CD18), we investigated the lineage specificity of beta-subunit mRNA expression in human hematopoietic cells. Relatively high levels of the beta-subunit mRNA transcript were detected in mature peripheral blood leukocytes, including granulocytes and both resting and PHA-activated T lymphocytes. In contrast, relatively low levels of this transcript were observed in EBV-transformed B cells, in the immature Jurkat T cell line, and in chronic myelogenous leukemia myeloblasts and lymphoblasts. The beta-transcript was undetectable in the K562 chronic myelogenous leukemia blast crisis cell line with erythroblastic characteristics and in cultured skin fibroblasts. Two acute myeloid leukemia samples displayed unusually high levels of this transcript, comparable to levels observed in mature PBL. beta-subunit mRNA expression appeared to be primarily confined to leukocytes. In all cells examined the levels of surface beta-Ag expression paralleled levels of beta-mRNA. PMID- 2904472 TI - Purification and partial characterization of the normal cellular homologue of the scrapie agent protein. AB - The scrapie agent protein (Sp33-37) is a degradation-resistant protein that aggregates into fibrils and amyloid plaques. This protein is derived from a normal cellular protein (Cp33-37). Understanding the mechanism responsible for the conversion of Cp33-37 to Sp33-37 may explain scrapie agent replication. Cp33 37 was extracted from normal hamster brain and purified 2700-fold by an immunoaffinity method. Both Cp33-37 purified from normal hamster brain and Sp33 37 purified from scrapie-affected hamster brain had apparent masses of 33-37 kilodaltons and displayed microheterogeneity characteristic of glycoproteins. Cp33-37 was completely digested by proteinase K under conditions that resulted in conversion of Sp33-37 to the protease-resistant fragment PrP27-30. Cp33-37 did not cause scrapie when inoculated intracerebrally into hamsters. Fractions containing purified Sp33-37 had average titers of greater than 10(11) LD50 of the scrapie agent/mg of protein; these titers were not diminished by proteinase K. These results indicate that altered sensitivity to proteolysis in vitro reflects an intrinsic difference between Sp33-37 and Cp33-37. PMID- 2904473 TI - Alpha 1-adrenoceptors in the albino rabbit ciliary process. AB - 3H-Prazosin and 3H-rauwolscine binding sites were identified in a membrane suspension prepared from albino rabbit iris + ciliary body. Scatchard analysis of saturation binding experiments demonstrated that both 3H-prazosin and 3H rauwolscine bind to a single population of binding sites with KD values of 0.87 nM and 5.33 nM, respectively. Bmax values of 65.7 and 198 fmol/mg protein were obtained for 3H-prazosin and 3H-rauwolscine, respectively. Displacement studies by several adrenergic agonists and antagonists indicated that 3H-prazosin and 3H rauwolscine labelled alpha 1- and alpha 2-adrenoceptors, respectively, in the iris + ciliary body. Epinephrine, norepinephrine and phenylephrine were able to stimulate the synthesis of 3H-inositol phosphates in ciliary processes labelled with 3H-inositol, with EC50 values of 2.4, 12 and 10 microM, respectively. The corresponding maximum stimulations of basal activity were 433, 430 and 283%, respectively. Phenylephrine behaved like a partial agonist in this assay. The norepinephrine response could be potently antagonized by prazosin (Ki = 27 nM), with rauwolscine being 285-fold less potent. An epithelial cell suspension was prepared from the ciliary process. Stimulation of phosphatidylinositol turnover by norepinephrine (0.1 mM) was observed, and this could be blocked by prazosin (10 microM), thus, indicating the presence of alpha 1-adrenoceptors, coupled to phosphatidylinositol turnover, in epithelial cells of the rabbit ciliary process. PMID- 2904474 TI - Effect of different antiglaucomatous drugs on ocular perfusion pressures. AB - In an attempt to elucidate whether antiglaucomatous drugs, especially beta blockers, affect systemic and/or ocular blood flow, we measured ocular perfusion pressures (PP), systemic blood pressure (BP) and heart rate in 50 healthy subjects before and after topical instillation of the following eye drops: timolol 0.5% (n = 10), betaxolol 0.5% (n = 10), carteolol 2% (n = 10), pilocarpine 2% (n = 10) and acetazolamide 750 mg per os (n = 10). The ocular perfusion pressures were measured by OODG as described by Ulrich. By means of this method--retinal and ciliary perfusion pressure can be recorded separately and simultaneously. Our results indicated that, in spite of a statistically significant decrease in IOP in all 5 groups, there was no change in retinal or ciliary perfusion pressure, heart rate or blood pressure in any of the groups except the carteolol subjects. The ocular perfusion pressures should be increased with reduction of the IOP when the systemic parameters remain unchanged. This was not the case in our experiments and therefore it can be suggested that a relative reduction in ocular perfusion pressure occurs with all agents and, in this respect, timolol and betaxolol did not affect ocular perfusion pressure more than pilocarpine and acetazolamide. Carteolol, however, produced a slight decrease (alpha less than 0.02) in ocular perfusion pressure, in spite of lowering of the IOP. PMID- 2904475 TI - Growth hormone (GH) secretion in the conscious rat: negative feedback of GH on its own release. AB - The negative-feedback effects of GH on its own secretion were studied in conscious male and female rats bearing indwelling double-bore venous cannulae. Intravenous infusions of human GH (hGH; 20-60 micrograms/h) or somatostatin (SS; 10 micrograms/h) were given while frequent serial microsamples of blood were withdrawn using an automatic blood-sampling system. In both sexes, i.v. infusions of hGH for 6 h inhibited endogenous GH secretory pulses, with a slow onset of the inhibition. There was no rebound GH secretion immediately following the removal of the hGH infusion, but spontaneous GH secretion gradually returned to normal. Infusions of hGH did not inhibit the pituitary GH response to repeated GH releasing factor (GRF) injections (1 microgram) given i.v. every 40 min to female rats. By contrast, infusions of SS, which also blocked spontaneous GH release, dramatically reduced the GH responses to serial GRF injections. When SS Infusions were stopped, the subsequent GRF-induced GH secretory responses were enhanced. These results show that GH can inhibit its own release when given by i.v. infusion to conscious male and female rats. Since GH responses to GRF are maintained during a GH infusion, the feedback effect of GH is unlikely to be exerted directly on the pituitary or by increasing SS release. Our results are consistent with the idea that GH feedback in the conscious rat involves an inhibition of GRF release. PMID- 2904476 TI - L3T4 effector cells in multiple organ-localized autoimmune disease in nude mice grafted with embryonic rat thymus. AB - Rat thymic grafts reconstituted T cell functions of BALB/c nude (nu/nu) mice to a considerable degree, but multiple organ-localized autoimmune diseases such as oophoritis and thyroiditis generally developed. The effector cell population in this autoimmune model was studied by adoptive transfer of the lesions into syngeneic nude mice. The transfer activity was not diminished when spleen cells were incubated with antiserum against rat cell antigen and C, but the activity was completely vanished by incubation with anti-Thy-1.2 plus C, indicating that the effector cells are T cells of mouse origin. Elimination of the L3T4+ subset virtually abolished the transfer activity, whereas that of the Lyt-2+ subset did not, indicating that the effector cells are L3T4+. Positive selection experiments by FACS also demonstrated that L3T4+ cells, but not Lyt-2+ cells, were capable of inducing the lesion, confirming the results with depletion experiments described above. PMID- 2904477 TI - A complicated nail puncture wound. PMID- 2904478 TI - Effects of epinephrine and norepinephrine on glucose release from chinook salmon (Oncorhynchus tshawytscha) liver incubated in vitro. AB - The effects of two catecholamines, epinephrine (EP) and norepinephrine (NE), on carbohydrate metabolism were studied by incubating chinook salmon liver in vitro. Basal release of glucose over the course of a 5-h incubation was 7.93 +/- 1.70 mumol/g dry weight. Both EP and NE (2 X 10(-7) M) stimulated glucose release rapidly during the first hour. After 5 h, EP and NE significantly increased glucose release over basal levels to 43.55 +/- 9.01 and 32.75 +/- 6.17 mumol/g dry weight, respectively. Epinephrine- and NE-stimulated glucose release was dose dependent, with a minimum effective dose of 10(-9) M. ED50 for both agents was approximately 2 X 10(-7) M; maximal stimulation occurred at 10(-5) M. No difference in potency between the two catecholamines was found. The effects of adrenergic agonists and antagonists were also studied. Alpha-agonists, methoxamine and phenylephrine, had no effect on glucose release. Isoproterenol, a beta-agonist, stimulated glucose release in a manner similar to EP. The beta antagonist, propranolol, inhibited both catecholamine- and isoproterenol stimulated glucose release. Alpha-antagonists (phentolamine, prazosin, and yohimbine) had no effect on either catecholamine- or isoproterenol-stimulated glucose release. Epinephrine and NE stimulate glycogen phosphorylase activity; propranolol inhibits catecholamine-stimulated phosphorylase activity. These results indicate that catecholamines stimulate glucose mobilization in salmon liver by promoting glycogenolysis mediated through beta-adrenergic receptors. PMID- 2904479 TI - Glutathione formation in Penicillium chrysogenum: stimulatory effect of ammonium. AB - Penicillium chrysogenum produced glutathione after growth in a defined medium containing 10 mM-NH4Cl as the sole source of nitrogen. The use of higher ammonium concentrations (100 mM) resulted in stimulation of growth and glutathione formation. In addition, increases in the intracellular pools of glutamate, alanine and glutamine, proportional to the amount of ammonium present in the medium were observed. Resting cell systems, prepared from cells previously grown with ammonium, were able to produce glutathione when incubated with ammonium or the amino acids glutamate, alanine and glutamine. A mutant lacking NADP-dependent glutamate dehydrogenase activity (which has a leaky phenotype on ammonium as sole nitrogen source) required glutamate to synthesize glutathione. Resting cell systems of this mutant, prepared from cells previously grown with ammonium, did not produce glutathione even when incubated with glutamate or glutamine. On the other hand, resting cell systems of this mutant produced glutathione if prepared from cells previously grown with glutamate. The addition of glutamate to resting cell systems of the wild-type strain stimulated the synthesis of gamma glutamylcysteine synthetase, the first enzyme of glutathione biosynthesis. PMID- 2904480 TI - Field bioassays of permethrin-treated uniforms and a new extended duration repellent against mosquitoes in Pakistan. AB - Field bioassays were conducted to evaluate the effectiveness of different treatment combinations of permethrin-impregnated clothing and a new extended duration repellent formulation of deet against natural populations of mosquitoes in Islamabad, Pakistan. Tests were initiated 2-2 1/2 hours prior to sunset and volunteers who wore the topical repellent applied it 8 hours earlier. The most effective treatment was a combination of wearing both the permethrin-impregnated clothing and the repellent on exposed skin. This combination provided 100% protection from bites whereas volunteers wearing only treated clothing received 57% protection. Those wearing only repellent received 89% protection, but, under the biting pressure observed, this was not significantly different from the treated clothing-repellent combination. PMID- 2904481 TI - Mosquitoes, medicine and memories. PMID- 2904482 TI - Techniques for mitochondrial and ribosomal DNA analysis of anopheline mosquitoes. AB - Methods are described for the isolation of mitochondrial and total cellular DNA from mosquitoes. The mitochondrial and ribosomal DNA restriction patterns could be detected in the total DNA of an individual mosquito by the use of cloned probes. DNA restriction analysis may prove to be a useful alternative to isozyme electrophoresis for the study of insect population genetics. PMID- 2904483 TI - A dynamic life table model of Psorophora columbiae in the southern Louisiana rice agroecosystem with supporting hydrologic submodel. Part 1. Analysis of literature and model development. AB - During the past decade, the rice agroecosystem and its associated mosquitoes have been the subject of an extensive research effort directed toward the development and implementation of integrated pest management (IPM) strategies. The objective of this work was to synthesize the literature and unpublished data on the rice agroecosystem into a comprehensive simulation model of the key elements of the system known to influence the population dynamics of Psorophora columbiae. Subsequent companion papers will present a validation of these models, provide an in-depth analysis of the population dynamics of Ps. columbiae, and evaluate current and proposed IPM strategies for this mosquito. This paper describes the development of 2 models: WaterMod: Because spatial and temporal distributions of surface water and soil moisture play a decisive role in the dynamics of Ps. columbiae, an essentially hydrological simulator was developed. Its purpose is to provide environmental inputs for a second model (PcSim) which simulates the population dynamics of Ps. columbiae. WaterMod utilizes data on weather, agricultural practices, and soil characteristics for a particular region to generate a data set containing daily estimates of soil moisture and depth of water table for 12 representative areas comprising the rice agroecosystem. This model could be used to provide hydrologic inputs for additional simulation models of other riceland mosquito species. PcSim: This model simulates the population dynamics of Ps. columbiae by using the computer to maintain a daily accounting of the absolute number of mosquitoes within each daily age class for each life stage. The model creates estimates of the number of eggs, larvae, pupae, and adults for a representative l-ha area of a rice agroecosystem. PMID- 2904484 TI - A dynamic life table model of Psorophora columbiae in the southern Louisiana rice agroecosystem with supporting hydrologic submodel. Part 2. Model validation and population dynamics. AB - In an earlier paper, the development of 2 simulation models designed to describe the interaction between key elements of the rice agroecosystem and the population dynamics of Psorophora columbiae were presented (Focks et al. 1988a). The objective of the work reported herein was to validate these models with field data. The first model (WaterMod) predicts soil hydrology conditions as a function of weather, agricultural practices, and soil characteristics for a variety of habitats found within the rice agroecosystem which are utilized by Ps. columbiae. Using a continuous series of hydrologic data collected in southwestern Louisiana during 1984 and 1985, WaterMod was demonstrated capable of adequately predicting runoff rates and the temporal timing of soil moisture and surface water. The second model (PcSim) simulates the population dynamics of Ps. columbiae based upon a host of variables including the output from WaterMod. This model was validated by comparisons made with density estimates from the literature on the temporal and spatial distribution of various life stages and by correspondence with light trap data gathered during the same time and location as the hydrologic data. PcSim was seen to respond appropriately to host animal densities and unusual meterological events occurring during 1984 and 1985 in southern Louisiana. A discussion is presented of the interaction between agricultural practices and certain key factors of the life history strategy of Ps. columbiae which permit the unusually successful exploitation of the rice agroecosystem by this species. A subsequent paper will use these models to evaluate current and proposed IPM strategies for this mosquito (Focks et al. 1988b). PMID- 2904485 TI - Trial of a quantified mass rearing method for Toxorhynchites splendens. PMID- 2904486 TI - Quantification of a nuisance mosquito problem in Florida. PMID- 2904487 TI - Clostridium perfringens infection in a total knee arthroplasty. A case report. AB - A 66-year-old woman with a painful total knee arthroplasty and turbid fluid aspirates had her prosthesis removed for a presumed diagnosis of infection. The intraoperative cultures were positive for Clostridium perfringens, and the patient did well after a course of intravenous antibiotics prior to reimplantation. Clostridium perfringens is a rare cause of pyarthrosis in both nonoperative and prosthetic joints. This report details the first case of clostridial infection involving a patient with a total knee arthroplasty. PMID- 2904488 TI - Modulation of a subthreshold calcium current by the neuropeptide FMRFamide in Aplysia neuron R15. AB - 1. The effect of the endogenous neuropeptide FMRFamide (Phe-Met-Arg-Phe-amide) on the Aplysia bursting pacemaker neuron R15 was studied. Brief local applications of FMRFamide, both on R15 somata in situ, and on R15 somata that were isolated and maintained in primary cell culture, cause a hyperpolarization of the membrane potential and a suppression of spontaneous bursting or beating pacemaker activity. 2. Two-electrode voltage-clamp experiments revealed that FMRFamide decreases the amplitude of an inward current, which activates with depolarization starting at a membrane potential less depolarized than the threshold for action potentials. Previous studies have established that this subthreshold inward current is carried by calcium and is essential for the generation of bursting pacemaker activity in Aplysia neurons. The effect of FMRFamide on the subthreshold inward current of R15 is blocked by divalent cation calcium channel blockers, such as cobalt and manganese, and is unaffected by changing the external concentration of potassium or chloride ions, or addition of blockers of the calcium-activated potassium current, such as external tetraethylammonium or internal EGTA. 3. The subthreshold calcium current of R15 is also decreased by dopamine and by an unidentified synaptic neurotransmitter. These substances mimic and occlude the action of FMRFamide on the subthreshold calcium current, suggesting that all three transmitters converge to affect the same population of calcium channels in neuron R15. 4. The subthreshold calcium current is enhanced by neurotransmitters that elevate cyclic AMP in R15, including serotonin, and the Aplysia neuropeptide egg-laying hormone (ELH). Likewise, the effect of FMRFamide on the subthreshold calcium current is enhanced by serotonin, ELH, and a cyclic AMP analog, suggesting that FMRFamide and cyclic AMP have antagonistic actions on the same population of calcium channels in neuron R15. 5. We conclude that the suppression of spontaneous bursting or beating pacemaker activity in neuron R15 by FMRFamide is due to a decrease in the subthreshold calcium current. The subthreshold calcium current in R15 is a common target for modulation by many different transmitters, acting via several distinct molecular mechanisms. PMID- 2904489 TI - Dual effects of theophylline on spontaneous transmitter release from frog motor nerve terminals. AB - Alkylxanthine drugs, such as theophylline, block adenosine receptors, inhibit phosphodiesterases and other enzymes, and cause the release of calcium from intracellular stores. Adenosine receptor blockade occurs at low micromolar concentrations of the drugs, while other effects occur in the millimolar concentration range. The effects of theophylline were tested on spontaneous transmitter release at the frog cutaneous-pectoris neuromuscular junction (NMJ). A change in the frequency, but not the amplitude, of miniature endplate potentials (mepps) was interpreted as a change in spontaneous transmitter release. In normal Ringer's, theophylline, at concentrations of 100 microM and 1 mM, theophylline had no consistent effect on spontaneous release. In contrast, theophylline produced dual effects on mepp frequency in hyperosmotic Ringer's. At 10 microM, theophylline depressed mepp frequency, while, at 100 microM and 1 mM, theophylline increased mepp rate. Since low micromolar concentrations of theophylline depressed spontaneous transmitter release, this action may result from adenosine receptor blockade and inhibition of a tonic, stimulatory effect of adenosine. This hypothesis was supported by the following experimental results: (1) Micromolar concentrations of theophylline reversed the effects of applied adenosine on neuromuscular transmission. (2) The inhibitory effect of theophylline was mimicked by 2 other alkylxanthines, 8-phenyltheophylline and 8-p sulfophenyltheophylline. These drugs may be more specific adenosine receptor antagonists than theophylline. (3) The inhibitory effect of theophylline was mimicked by adenosine deaminase, an enzyme that breaks down and inactivates adenosine. (4) The depressant action of theophylline was masked by the addition of adenosine deaminase to the hyperosmotic Ringer's. Application of adenosine to the frog NMJ reduces spontaneous transmitter output.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2904490 TI - Presynaptic long-term facilitation at the crayfish neuromuscular junction: voltage-dependent and ion-dependent phases. AB - Long-term facilitation (LTF) of synaptic transmission was investigated in the crayfish opener muscle to determine the factors necessary for its induction and expression. LTF was induced without action potentials by intracellular depolarization of presynaptic nerve terminals. Following induction, the synaptic transmission was enhanced by about 80% for a period of several hours. Intracellular recordings from pre- and postsynaptic cells, combined with ionic and pharmacological tests, permitted dissection of LTF into 2 phases: an initial tetanic phase that depended on the presence of both sodium and calcium ions and a subsequent long-lasting phase. This latter long-lasting enhancement of synaptic transmission was induced by repeated depolarizations of synaptic terminals but did not depend on the influx of sodium or calcium ions or on intracellular release of calcium ions. Both tetanic and long-lasting phases of LTF are attributable to activity of a single neuron, i.e., they are homosynaptic phenomena. Furthermore, LTF is associated with an increase of quantal release, whereas the size of quanta remains unchanged. During the long-lasting phase of LTF, the nerve terminal releases more transmitter for a given depolarization than before induction of LTF. Thus, the locus of LTF is presynaptic. Our findings suggest the presence of a voltage-dependent mechanism in the presynaptic membrane different from voltage-gating of Na or Ca channels. Such a mechanism may be important in the establishment of long-lasting synaptic changes at the crayfish neuromuscular junction and perhaps in other neural systems. PMID- 2904491 TI - Characterization of antinociception produced by glutamate microinjection in the nucleus tractus solitarius and the nucleus reticularis ventralis. AB - Four experiments examined the role of the nucleus tractus solitarius (NTS) and subjacent nucleus reticularis ventralis (NRV) in the production of antinociception. Experiment 1 showed that microinjection of glutamate (50 nmol) into the caudal NTS resulted in inhibition of the tail-flick reflex, hypotension, and mild bradycardia, whereas microinjection of glutamate into the rostral NTS resulted only in hypotension and mild bradycardia. Microinjections of glutamate into the NRV resulted in inhibition of the tail-flick reflex, hypertension, and mild bradycardia. Experiment 2 demonstrated that the magnitude of the antinociceptive and cardiovascular responses resulting from glutamate microinjections into both the depressor and pressor regions were dose dependent. Experiment 3 showed that the antinociceptive effects resulting from microinjections of glutamate into either the depressor or pressor regions could not be antagonized by phentolamine (30 micrograms), methysergide (30 micrograms), or naloxone (30 micrograms) alone, but the combined intrathecal administration of phentolamine and methysergide (7.5, 15, or 30 micrograms of each) attenuated the antinociception resulting from microinjection of glutamate into either depressor or pressor regions in a dose-dependent fashion. Experiment 4 showed that systemic administration of hexamethonium blocked the pressor response produced by microinjection of glutamate into the NRV but did not reduce the antinociceptive effect of the microinjection. These findings are consistent with a role for the NTS and NRV in the production of antinociception. PMID- 2904492 TI - Do N-methyl-D-aspartate receptors mediate synaptic responses in the mudpuppy retina? AB - Whole-cell recordings of amacrine and ganglion cells in the superfused retina eyecup preparation of the mudpuppy were obtained in order to determine which excitatory amino acid receptor (EAAR) subtype mediates the synaptic responses of these neurons. All third-order retinal neurons tested were depolarized by kainic acid (KA, N-methyl-D-aspartate (NMDA), and quisqualate (QQ). The responses evoked by NMDA were blocked by the addition of D-2-amino-5-phosphonovaleric acid (D-AP5) and D-2-amino-7 phosphonoheptonoic acid (D-AP7) to the perfusate. When the actions of exogenously applied NMDA were completely blocked by D-AP5 and D-AP7, the light-evoked responses of inner retinal neurons persisted without any apparent reduction or, alternatively, a slight enhancement of the response was observed. Light-evoked responses of bipolar, amacrine, and ganglion cells associated with the On pathway were attenuated by L-AP5 in a manner similar to its lower-order homolog L-2-amino-4-phosphonobutyrate (AP4); nevertheless, L-AP5 was not an effective NMDA antagonist. Although synaptic transmission between retinal second- and third-order neurons appears to be mediated by EAARs, the NMDA receptor does not appear to play a prominent role under our experimental conditions. Nevertheless, our results suggest that the racemic mixture of AP5 should not be used as an NMDA antagonist in retinal research, due to the AP4-like actions of its L-enantiomer. PMID- 2904493 TI - Neuroprotective effects of MK-801 in vivo: selectivity and evidence for delayed degeneration mediated by NMDA receptor activation. AB - The ability of the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 to prevent neuronal degeneration in the rat striatum and hippocampus caused by intracerebral injection of excitotoxins has been examined. Excitotoxic damage was assessed after 7 d, using histological and biochemical [choline acetyltransferase (ChAT) glutamate decarboxylase (GAD)] measurements. Systemically administered MK-801 was found to protect against neurodegeneration caused by NMDA (200 nmol) and the naturally occurring NMDA receptor agonist quinolinate (120-600 nmol) but not against that induced by kainate (5 nmol) or alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA; 50 nmol), indicating a selectivity for NMDA receptor-mediated neuronal loss. Neurotoxicity caused by NMDA (200 nmol) or quinolinate (200 nmol) was prevented by MK-801 (1-10 mg/kg, i.p.) administered in a single dose after excitotoxin injection. In the striatum, significant protection of cholinergic neurons (assessed by ChAT measurements) was observed when MK-801 was given up to 5 hr after injection of NMDA or quinolinate, whereas protection of GABAergic neurons (assessed by GAD measurements) was obtained up to 2 hr. The results suggest that GABAergic neurons degenerate more rapidly than cholinergic neurons. The competitive NMDA receptor antagonist 3-[(+/ )-2-carboxypiperazin-4-yl]-propyl-1-phosphonate (100 mg/kg, i.p.) gave partial protection of striatal neurons when administered 1 hr after quinolinate injection. In the rat hippocampus, administration of 10 mg/kg MK-801 i.p. 1 hr after quinolinate injection caused almost complete protection of pyramidal and granule neurons, whereas the degeneration of CA3/CA4 pyramidal neurons caused by kainate injection was unaffected. These observations indicate that neurons in rat striatum and hippocampus do not die as an immediate consequence of exposure to high concentrations of NMDA agonists but that a delayed process is involved that requires NMDA receptor activation. In this respect, intracerebral injections of NMDA agonists may mimic the pathological changes that are thought to occur in the brain following periods of cerebral ischemia, where delayed neuronal degeneration occurs. PMID- 2904494 TI - Differential expression of preproenkephalin and preprodynorphin mRNAs in striatal neurons: high levels of preproenkephalin expression depend on cerebral cortical afferents. AB - Preproenkephalin and preprodynorphin mRNAs can be detected by in situ hybridization in medium-sized striatal neurons in normal rats and in rats with unilateral cerebral cortical lesions. Hybridization of 35S-labeled oligonucleotide cDNAs complementary to specific regions of each mRNA reveals that preproenkephalin-expressing neurons are more numerous than cells expressing preprodynorphin. Hybridization densities above enkephalin-positive neurons are also more than twice those noted above preprodynorphin-expressing cells. Northern analyses of mRNA extracted from the striatum are consistent with these relationships. The striatal preproenkephalin hybridization densities are decreased ipsilateral to cerebral cortical lesions; this change evolves largely between 1 and 5 d following the lesion. Striatal preproenkephalin mRNA is thus more prominent than preprodynorphin mRNA and depends on cerebral cortical inputs for its full expression. PMID- 2904495 TI - Medullary regions mediating atonia. AB - Electrical stimulation studies have implicated the medial medulla in the inhibition of muscle tone. In the present report we present evidence for suppression of muscle tone by chemical activation of the medial medulla. We find 2 distinct zones within the classically defined medial medullary inhibitory area. A rostral region corresponding to the nucleus magnocellularis (NMC) is sensitive to glutamate. Atonia produced by activation of this region is mediated by non NMDA receptors. A caudal region, corresponding to the nucleus paramedianus (NPM) is sensitive to ACh. Atonia produced by activation of this region is mediated by muscarinic receptors. Activation of these regions both in acute decerebrate and intact cats suppresses muscle tone. We find that the cholinoceptive dorsolateral pontine region, previously implicated in atonia control, can be activated by glutamate-sensitive non-NMDA receptors. Microinjection of atropine into the NPM or of glutamylglycine into the NMC blocks atonia elicited by pontine carbachol injection. The medullary regions identified here are hypothesized to mediate the suppression of muscle tone that occurs in rapid eye movement sleep and in cataplexy and may have a role in postural control in waking. PMID- 2904496 TI - Genetic characterization and use of a restriction fragment length variant in the hypotrichous ciliate Euplotes crassus. AB - Two forms of a macronuclear DNA molecule differing in the presence or absence of a restriction endonuclease recognition site have been detected in the hypotrichous ciliate Euplotes crassus. Through a series of genetic crosses the two forms were shown to be allelic, being derived from a single micronuclear genetic locus. This restriction fragment length variant (RFLV) was used as a genetic marker to determine that the migratory and stationary pronuclei generated during mating can be genetically non-identical. In addition, the RFLV was used to investigate the efficiency of processing of the alternate alleles during macronuclear development and their subsequent transmission during vegetative growth. Little or no bias in the processing and/or amplification of the two alleles was observed during macronuclear development. During vegetative growth, however, changes in the relative amounts of the two alleles were observed. PMID- 2904497 TI - Maintenance of integrity, viability, and adhesion of Entamoeba histolytica trophozoites in different incubation media. AB - We have determined the integrity, viability and adhesion of Entamoeba histolytica HK9 and HM1 trophozoites during their incubation in two basal culture media (TP and TYI) and three saline media ("maintenance medium" MM-1 and two others buffered with HEPES). In basal culture media, more than 70% of the trophozoites maintained their integrity and adhesion to human red blood cells (RBC) for up to 4 h, and the proportion of those excluding Trypan blue decreased slowly after 2 h. In saline media, the number of ameba-RBC complexes reached a maximum after 20 30 min and then decreased rapidly (and fastest in MM-1), less than 10% of the amebae were intact after 3-4 h, and dye exclusion fell abruptly from the start of incubation. The number of ameba-RBC complexes formed and the rate of adhesion were highest in basal TP medium. Normal nonvacuolated refringent (NVR) trophozoites deteriorated progressively in all media--although much faster in the saline ones--to vacuolated refringent (VR), nonrefringent, and disrupted. Trypan blue was excluded by all NVR and a fraction of the VR trophozoites. Horse serum helped to maintain ameba integrity and viability, but inhibited adhesion in a concentration-dependent manner. We conclude that E. histolytica trophozoite integrity and adhesion are adequately preserved and should be characterized only in basal culture media, that refringence without vacuolization is a more stringent characteristic of ameba quality than Trypan blue exclusion, and that some serum component inhibits ameba adhesion. PMID- 2904498 TI - Successful replantation of a foot with satisfactory recovery: a case report. AB - A severed foot in a 51-year-old man was successfully replanted. One year after operation, two-point discrimination was 15 mm on the plantar aspect and 25 mm on the dorsal side. The patient can walk long distances and go up and down stairs without and supportive aids. PMID- 2904499 TI - Effect of administration of an alpha 2-adrenergic agonist, xylazine, on pulsatile gonadotrophin secretion in anoestrous horse mares. AB - Two experiments were performed to test the hypothesis that the seasonal suppression of gonadotrophin pulse frequency in anoestrous horse mares reflects inhibitory neural mechanisms. In a preliminary experiment (Exp. 1) conducted in February, 4 anoestrous mares were sedated by repeated intravenous injections of xylazine, an alpha 2-adrenergic receptor agonist. On the day of treatment, 1-2 LH pulses were observed in xylazine-treated mares. In contrast, during a 12-h period only 1/8 untreated control mares exhibited a LH pulse. In Exp. 2, the effect of xylazine-induced sedation on pulsatile gonadotrophin release was examined in 4 anoestrous mares on two occasions before (18 November and 9 December) and after (23 December and 6 January) an abrupt, artificial increase in day length. Treatment with xylazine was associated with an overall increased FSH (P less than 0.01) and LH (P less than 0.05) pulse frequency, compared with that observed during 12-h pretreatment periods. To evaluate an effect of treatment at the various time during the experimental period, the change in FSH pulse frequency was analysed, since occasionally FSH pulses were unaccompanied by a change in serum LH values indicative of a LH pulse. On two occasions before increased daylength only 1/4 and 3/4 mares exhibited an increase in FSH pulses; in contrast, 14 days after increased daylength (23 December), 4/4 mares exhibited increased FSH pulse frequency associated with treatment. After 27 days of increased daylength (6 January), endogenous FSH pulse frequency was greater than before increased daylength and treatment with xylazine was unaccompanied by a further increase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2904500 TI - Cyclosporin-mediated increase in kidney glutathione and effects on gamma-glutamyl cycle enzymes. AB - The unprecedented ability of cyclosporin A, when given for six days at a dose of 25 mg/kg/d or 50 mg/kg/d, to cause a marked and sustained increase in renal glutathione (GSH) concentration in rat kidney is described. This response was particular to the kidney insofar as the GSH concentration in the liver was not increased in response to a lower dose of cyclosporin and was decreased in the liver of animals treated with the higher dose of the drug. The increase in kidney GSH concentration did not appear to be due to an increased rate of production or to an inhibition of the degradation of the tripeptide. This suggestion is based on the finding that the activities of the GSH synthesis pathways, GSSG-reductase and gamma-glutamylcysteine synthetase, were unchanged or decreased, respectively, and those of the catabolic enzymes, GSH-peroxidase and gamma glutamyltranspeptidase, were unchanged or increased, respectively. It is suggested that the elevation of renal GSH content in the face of diminished synthetic capacity and an apparent increased utilization may result from an enhanced uptake of GSH as the result of alterations caused by cyclosporin in the renal transport system. PMID- 2904501 TI - Whooping cough diagnosis: a clinical evaluation of complementing culture and immunofluorescence with enzyme-linked immunosorbent assay of pertussis immunoglobulin A in nasopharyngeal secretions. AB - Pernasal aspirate (PNA) was obtained from 543 children during a 6-month period when whooping cough was prevalent. Three tests for diagnosing pertussis were performed on the PNA: (a) examination of direct smears by immunofluorescence (IF) for Bordetella pertussis; (b) culture; and (c) estimation of B. pertussis specific immunoglobulin-A antibody (P-IgA) by an enzyme-linked immunosorbent assay (ELISA). On clinical review, 395 children were assessed to have had pertussis (P children) and 148 children not to have had pertussis (non-P children). The non-P children comprised 66 admitted to hospital for acute respiratory infections and 82 outpatients suspected of having pertussis. Analysis of the results of the tests on the PNAs of the non-P children helped to assess the P-IgA test. The analysis showed that artificial immunisation against pertussis did not affect the antibody results, but that non-specific positive results occur requiring the labelling of many P-IgA results as "doubtful". Among the 395 P children, 36% yielded positive cultures and more than half of these also had positive IF tests. The ELISA for P-IgA was positive in 24% of all the P children, equivalent to nearly 40% of the culture-negative P children. For the 148 non-P children, IF and culture-negative by definition, the P-IgA test was positive in 9%. The antibody test result was doubtful in 28% of the P children and in 40% of the non-P children. Estimation of P-IgA antibodies in PNA is a useful and economic complement to culture and IF in the diagnosis of pertussis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2904502 TI - [The effect of bunazosin on hypertension during anesthesia; effectiveness of nasal instillation]. PMID- 2904503 TI - Comparison of inhibitory effects of calcium channel blockers and that of a calmodulin antagonist in strips of mesenteric arteries from spontaneously hypertensive and normotensive rats. AB - Effects of calcium channel blockers and of calmodulin antagonist on the contractile responses to norepinephrine (NE) were compared between strips of mesenteric arteries from 6- and 14-week-old spontaneously hypertensive rats (SHR) and age-matched, normotensive Wistar-Kyoto rats (WKY). The ratio of the maximum contraction developed by NE to that by 60 mM KCl was significantly increased in strips from 14-week-old SHR. Niludipine, verapamil and diltiazem antagonized the maximum NE contraction to a greater extent in strips from 14-week-old SHR than in those from the WKY. However, the antagonism by niludipine of the KCl- or caffeine induced contraction was not significantly different between the strips from 14 week-old SHR and those from WKY. In strips from 6-week-old rats, there was no difference in the antagonism by niludipine of the maximum NE contraction. On the other hand, the effect of W-7 on the maximum NE contraction was not significantly different between the strips from 14-week-old SHR and those from WKY. Schild plot analyses demonstrated that alpha 1-adrenoceptors were the same for the strips from SHR and WKY. These results suggest that the enhanced maximum NE contraction in the mesenteric artery from 14-week-old SHR reflects the increased transmembrane influx of calcium, and the activity of calmodulin seems to be the same for the two strains. PMID- 2904504 TI - The organization of the cholinergic synapse. PMID- 2904505 TI - [Selective alpha-adrenoblockaders in the treatment of stenocardia patients]. PMID- 2904506 TI - [Adrenergic regulation and problems of cardiovascular pathology]. PMID- 2904508 TI - [1. European nursing conference. With combined effort into the future]. PMID- 2904507 TI - Renin secretion responsiveness: understanding the efficacy of renin-angiotensin inhibition. PMID- 2904509 TI - [European Conference on Nursing, Vienna, 21-24 June 1988. The objectives have been met]. PMID- 2904510 TI - A sensitive method for immunocytochemical detection of P-glycoprotein in multidrug-resistant human ovarian carcinoma cell lines. AB - P-glycoprotein, a molecular weight 170 kilodalton membrane component can be accurately detected in a series of human ovarian carcinoma cells with increasing degrees of multidrug resistance by using a modified immunoperoxidase "sandwich" method. Drug-resistant derivatives were selected from a drug-sensitive parent ovarian carcinoma cell line, SKOV3, by continuous exposure to increasing concentrations of the cytotoxic drug vincristine. These cells had corresponding overexpression of P-glycoprotein demonstrable at both protein and mRNA levels. Monoclonal antibodies against P-glycoprotein localized staining for P glycoprotein to the plasma membrane and the Golgi region in individual drug resistant cells, in proportion to their P-glycoprotein expression. P-glycoprotein was not demonstrable in drug-sensitive SKOV3 cells by either immunoblotting or immunocytochemical staining methods. The immunocytochemical staining method allowed detection of P-glycoprotein in the least drug-resistant cell line with as low as 8-fold relative resistance to vincristine. This method is as sensitive as Northern blot, and more sensitive than standard Western blot in detection of P glycoprotein. We conclude that this highly sensitive immunocytochemical staining method for P-glycoprotein can be suitable for determination of P-glycoprotein expression in biopsy samples of tumors, and it can be a powerful diagnostic and prognostic tool in the study of the natural history of drug resistance. This may have important applications in the clinical management of cancer chemotherapy. PMID- 2904511 TI - Description and analysis of differential sensitivity to glucocorticoids in Fao cells. AB - This study shows that the derived hepatoma cell line Fao displays different sensitivities for glucocorticoid induction of tyrosine aminotransferase (TAT), alanine aminotransferase (AAT) and gamma-glutamyltransferase (GGT). This was seen in the different behaviors of nine steroids with respect to these three effects: (1) in the presence of full agonists (dexamethasone or deacylcortivazol), half maximal induction of GGT occurred at approx 5- to 6-fold higher agonist concentrations than those required for half-maximal induction of AAT and TAT; (2) in the presence of full antagonists (RU 486, R5020, or progesterone) the GGT response induced by an equal agonist concentration was inhibited at concentrations approx 4- to 5-fold lower than those required for an equivalent inhibition of TAT response; (3) in the presence of cortexolone, deoxycorticosterone, 11 beta-hydroxyprogesterone and dexamethasone-3'-oxetanone, there was a partial agonistic effect (30-50%) on TAT and AAT responses, whereas there was a mainly antagonistic effect (very weak agonistic effect: 0-10%) on GGT response; (4) regardless of the steroid or its full or partial agonist activity, a given TAT induction level (50%, for example) always corresponded to the same AAT and GGT induction levels (50 and 10% respectively). We provide evidence showing that the three above-mentioned biological responses are mediated via the same type of glucocorticoid receptor binding site. Consequently, this differential behavior probably originates from a phenomenon occurring after the common steps (activation, translocation) that follow the formation of the steroid receptor complex. This leads us to propose a model in which this phenomenon is assumed to originate from a difference in the affinities of the activated receptor for the nuclear acceptor sites of the TAT and GGT genes. PMID- 2904512 TI - Quantitative immunocytochemistry using an image analyzer. II. Concentration standards for transmitter immunocytochemistry. AB - Image analyzers can measure both the optical density and geometry of immunocytochemically labeled cells and fibers, as reviewed in a companion paper (Mize et al., 1988). In this paper, we report a procedure which allows us to estimate the concentration of a neurotransmitter based upon the optical density of antibody labeling produced by immunocytochemistry. To accomplish this, we developed a standard which binds conjugated neurotransmitters. Several artificial media for the standard were compared, including agar, gelatin, and agar-gelatin. A 3% agar matrix was found to be most suitable because it cut well and was nearly transparent. The agar sections were activated with cyanogen bromide/acetonitrile to promote coupling to the antigen. To test the standard, we used gamma aminobutyric acid (GABA) conjugated to bovine serum albumin (BSA) as the antigen. The antibody was directed against this conjugate. Activated agar sections were incubated in serial dilutions of the tritium-labeled GABA/BSA conjugate. The radioactivity of some of these sections was measured to estimate the amount of coupled antigen. The remaining sections were incubated in the GABA antibody and processed for immunocytochemistry. The optical density of these sections was measured with an image analyzer. A linear relationship was found between GABA concentration and optical density over a range of at least 0.01 to 1 nmol/mg of agar. These results show that the concentration of bound GABA can be estimated from the optical density of sections labeled by antibody immunocytochemistry. The applicability of this technique to fixed brain tissue is discussed. PMID- 2904513 TI - Cluster formation in PHA-stimulated mononuclear cells from peripheral blood: effects of colcemid and taxol. AB - Mononuclear cells from peripheral blood were incubated with phytohemagglutinin (PHA) for 24-72 hours. The cells formed dense cell clusters with firm cell-to cell attachment and signs of cell communication, proliferation and differentiation. At the end of a 72-hour period of incubation, the test preparations were treated for 90 minutes with the classical microtubule antagonist Colcemid and the new microtubule antagonist taxol. Taxol produced approximately twice as many mitoses as Colcemid. Chromosomes in taxol-blocked mitoses appeared to be more contracted than chromosomes in Colcemid-blocked mitoses. It is suggested that one beneficial side effect of Colcemid preparation of chromosomes is stretching due to microtubule disassembly. PMID- 2904514 TI - Retroviruses: leukemia and immunosuppression. The Yohei Ito memorial lecture. PMID- 2904515 TI - Modulation of hemopoiesis by novel stromal cell factors. AB - The microenvironment of the bone marrow in mammals is a crucial site for the maintenance of a pluripotent hemopoietic stem cell pool. Our previous studies and present findings support the notion that both this function and the fine architecture of hemopoietic organs, i.e., the spatial arrangement of blood cells within the tissue, may be directed by stromal cells. Despite the ability of cloned stromal cells to support prolonged hempoiesis and maintenance in vitro of stem cells with high radioprotective ability, they are a poor source of colony stimulating factor-1 (CSF-1) and do not secrete the other species of CSF. Furthermore, cultured stromal cells antagonize the activity of CSF. It is proposed that stromal cell factors distinct from known CSFs, regulate stem cell renewal. An additional phenomenon that is mediated by stromal cells and can not be attributed to CSF, is their ability to specifically inhibit the accumulation of cells of particular lineage and stage of differentiation. A glycoprotein that inhibits the growth of plasmacytomas but not a variety of other cell types was isolated from one type of cloned stromal cells. Such specific inhibitors may account for the control of cell localization in the hemopoietic system. PMID- 2904516 TI - [Study of immunologic parameters in parenteral drug addicts (PDA) with condylomata acuminata]. AB - A study is made of the state of cell and humoral immunity in parenteral drug addicts both with and without genital warts. The results reveal alterations in the lymphocyte subpopulations, with a decrease in the T-helper/T-suppressor (T4+/T8+) ratio of both groups of patients. These alterations were more pronounced in those patients with genital warts (p less than 0.05). The alterations in humoral immunity, expressed as a hypergammaglobulinemia IgG and IgM, were similar in both groups. None of the immunological parameters were affected by the extension of the lesions, though the T4+/T8+ ratio was found to decrease with increasing length evolution of the lesions. It would be convenient to perform longitudinal studies of these preliminary data to evaluate the effect of human papilloma virus (HPV) on the immune system. PMID- 2904517 TI - [Treatment with beta-blockaders after infarction--selection of patients, time and economics]. PMID- 2904518 TI - [Therapeutic alternatives in hypertension: beta-blockaders for the poor and psychotherapy for the rich?]. PMID- 2904520 TI - [A symposium of the Swedish Medical Society's ethical delegation: Ethical questions and transplantation]. PMID- 2904519 TI - [Identification of genetic carriers in familial amyloidosis with polyneuropathy is possible with the DNA technic]. PMID- 2904521 TI - Ocular fundus lesions in divers. AB - Retinal fluorescein angiography was used to examine the ocular fundi of 84 divers. The retinal capillary density at the fovea was low and microaneurysms and small areas of capillary nonperfusion were seen. The divers had significantly more abnormalities of the retinal pigment epithelium than a comparison group of non-divers. Furthermore, the prevalence of fundus abnormality was related to length of diving history. All observed changes were consistent with the obstruction of the retinal and choroidal circulations. Such obstruction could be due either to intravascular bubble formation during decompression, or to altered behaviour of blood constituents and blood vessels in hyperbaric conditions. PMID- 2904522 TI - Allele loss on short arm of chromosome 17 in breast cancers. AB - Tumour and blood leucocyte DNA from a consecutive series of patients with primary breast cancer was probed to detect deletions at six polymorphic loci in tumour tissue. The highest frequency of allele loss (61%) was found with the probe YNZ22, which detects a sequence on the short arm of chromosome 17 (at p13.3). The previously reported loss of alleles at the Harvey ras locus (11p14) in about 20% of breast tumours was confirmed. The putative breast tumour suppressor gene on 17p may be the same as that already noted for colon and lung cancers and it is suggested that deletion of this gene is one of a cumulative series of lesions involving genetic changes in the evolution of breast cancer. The findings identify chromosome 17p as a candidate region for linkage studies in breast cancer families. PMID- 2904523 TI - Support for adrenaline-hypertension hypothesis: 18 hour pressor effect after 6 hours adrenaline infusion. AB - In a double blind, crossover study 6 h infusions of adrenaline (15 ng/kg/min; 1 ng = 5.458 pmol), noradrenaline (30 ng/kg/min; 1 ng = 5.911 pmol), and a 5% dextrose solution (5.4 ml/h), were given to ten healthy volunteers in random order 2 weeks apart. By means of intra-arterial ambulatory monitoring the haemodynamic effects were followed for 18 h after the infusions were stopped. Adrenaline, but not noradrenaline, caused a delayed and protracted pressor effect. Over the total postinfusion period systolic and diastolic arterial pressure were 6 (SEM 2)% and 7 (2)%, respectively, higher than after dextrose infusion (ANOVA, p less than 0.001). Thus, "stress" levels of adrenaline (230 pg/ml) for 6 h cause a delayed and protracted pressor effect. These findings are strong support for the adrenaline-hypertension hypothesis in man. PMID- 2904524 TI - Simultaneous isolation of HIV-1 and HIV-2 from an AIDS patient. AB - Two distinct human immunodeficiency viruses, HIV-1SF480 and HIV-2UC2 were isolated simultaneously from the blood of an Ivory Coast patient with AIDS. The HIV subtypes were segregated by their differential ability to infect established human cell lines and by the cell surface expression of type-specific viral antigens. The viruses could be distinguished by both immunoblot and Southern blot analyses. The results indicate that an individual can be infected by both HIV subtypes. PMID- 2904525 TI - Improvement of hepatic encephalopathy treated with flumazenil. AB - The effects of the benzodiazepine antagonist flumazenil were studied in 20 episodes of hepatic encephalopathy (HE) in 17 patients with acute (n = 9) or chronic (n = 8) liver failure who had not responded to conventional therapy. Patients with a history of benzodiazepine intake were excluded. Changes in HE stage, in Glasgow coma scale, and in somatosensory evoked potentials were measured. In 12 of 20 episodes HE stage improved. The response to treatment occurred rapidly (within 3-60 min). In 8 of these 12 episodes HE worsened 0.5-4 h after treatment. In 5 of the 8 episodes that did not respond to flumazenil patients had clinical evidence of brain oedema. Flumazenil may be valuable in the treatment of HE in acute and chronic liver failure. PMID- 2904526 TI - Remission induction in non-Hodgkin lymphoma with reshaped human monoclonal antibody CAMPATH-1H. AB - A genetically reshaped human IgG1 monoclonal antibody (CAMPATH-1H) was used to treat two patients with non-Hodgkin lymphoma. Doses of 1-20 mg daily were given intravenously for up to 43 days. In both patients lymphoma cells were cleared from the blood and bone marrow and splenomegaly resolved. One patient had lymphadenopathy which also resolved. These effects were achieved without myelosuppression, and normal haemopoeisis was restored during the course of treatment, partially in one patient and completely in the other. No antiglobulin response was detected in either patient. CAMPATH-1H is a potent lympholytic antibody which might have an important use in the treatment of lymphoproliferative disorders and additionally as an immunosuppressive agent. PMID- 2904527 TI - Xamoterol: stabilising the cardiac beta receptor? PMID- 2904528 TI - Shackled, shameful, and shoddy. PMID- 2904529 TI - Valproate, spina bifida, and birth defect registries. PMID- 2904530 TI - Diurnal variation in platelet aggregation responses. PMID- 2904531 TI - Recurrent respiratory papillomatosis. PMID- 2904532 TI - Evaluation of a structured treatment and teaching programme on non-insulin dependent diabetes. AB - A structured treatment and teaching programme for non-insulin-treated non-insulin dependent (type 2) diabetes was evaluated prospectively in general practice. The four group sessions were mainly conducted by paramedical personnel. 65 patients from five general practices were assessed at the start of the programme and 50 (mean age 65 years, diabetes duration 7 years) completed the 1 year follow-up (intervention group). The control group consisted of 49 patients (mean age 63 years, diabetes duration 7 years) from three other general practices without the programme. In the intervention group the percentage of patients receiving sulfonylureas fell from 68% at the start of the study to 38% after 1 year (mean difference 30%, 95% confidence interval [CI] 16-44%); the mean weight loss was 2.7 kg (95% CI 1.6-3.8 kg), and non-fasting triglycerides were reduced by 0.77 mmol/1 (95% CI 0.35-1.19 mmol/l); and glycosylated haemoglobin remained unchanged (7.1% of total haemoglobin). In the control group none of these indices was changed during the study year, and 10% of patients started insulin treatment. The structured treatment and teaching programme improved the overall quality of patient care in elderly non-insulin-dependent diabetic patients treated by general practitioners. PMID- 2904533 TI - Reversible ceftriaxone-associated biliary pseudolithiasis in children. AB - Serial abdominal ultrasonography was performed in 37 children being treated with ceftriaxone for serious infections. Biliary concrements developed in 16 patients, causing symptoms in 3, one of whom also had urolithiasis with renal colic and obstructive ureteropyelectasia. After cessation of ceftriaxone treatment, ultrasound abnormalities and symptoms gradually disappeared, with complete sonographic resolution after 2 to 63 days. PMID- 2904534 TI - Nasal continuous positive airway pressure in Pneumocystis carinii pneumonia. AB - 10 cm H2O of nasal continuous positive airway pressure (CPAP) was applied in nine subjects with Pneumocystis carinii pneumonia and the acquired immunodeficiency syndrome, all of whom had presented with bilateral pulmonary infiltrates and hypoxaemia. The procedure was tolerated well by eight patients and none of the nine had complications. 20 minutes of nasal CPAP without supplemental oxygen increased mean PaO2 from 55.9 to 68.4 mm Hg and decreased the calculated alveolar arterial oxygen gradient from 48.3 to 34.3 mm Hg. In one patient who was breathing oxygen at 4 litres per minute, PaO2 increased by 35 mm Hg. Nasal CPAP could be a useful method for augmenting oxygenation in P carinii pneumonia. PMID- 2904535 TI - Reversed polarity of vasculocutaneous potential and neonatal necrotising enterocolitis. PMID- 2904536 TI - Haemodilution in renal transplantation in patients on erythropoietin. PMID- 2904537 TI - Treatments for neurotic disorders. PMID- 2904538 TI - Licensing synthetic intracervical tents. PMID- 2904539 TI - Birthweight and neonatal mortality. PMID- 2904540 TI - Food intolerance and rheumatoid arthritis. PMID- 2904541 TI - Changes in body weight between consecutive pregnancies. PMID- 2904542 TI - Cholinergic side-effects of tetrahydroaminoacridine. PMID- 2904543 TI - Salmonella enteritidis phage type 4 and hens' eggs. PMID- 2904544 TI - Peripheral facial paralysis indicating HIV infection. PMID- 2904545 TI - HIV, glue ear, and adenoidal hypertrophy. PMID- 2904546 TI - Cat scratch disease, bartonellosis, and Kaposi sarcoma. PMID- 2904547 TI - Home intravenous immunoglobulin therapy. PMID- 2904548 TI - Inhibition of cholinesterases by pentamidine. PMID- 2904549 TI - Italian epidemic of waterborne tularaemia. PMID- 2904550 TI - Is inactivated poliovaccine more expensive? PMID- 2904551 TI - Heat-stable versus heat-labile vaccines. PMID- 2904552 TI - Management of dysentery by community health workers. PMID- 2904553 TI - Antibody responses to human herpesvirus 6 and other herpesviruses. PMID- 2904554 TI - Parvovirus-associated thrombocytopenic purpura. PMID- 2904555 TI - Clinical trial numbers and confidence intervals of pre-specified size. PMID- 2904556 TI - Danish experience of statutory right of patients to access hospital records. PMID- 2904557 TI - Better surgeons get better results. PMID- 2904558 TI - Graves' disease: the thyroid not the pancreas. PMID- 2904559 TI - ICRF appeals. PMID- 2904560 TI - Paying for extended Medicare. PMID- 2904561 TI - Specific detection of Taenia saginata eggs by DNA hybridisation. PMID- 2904562 TI - Non-surgical left-atrial aortic bypass. PMID- 2904563 TI - Screening for aortic aneurysm. PMID- 2904564 TI - Pelvic irradiation and tamoxifen as risk factors for carcinoma of corpus uteri. PMID- 2904565 TI - Erythromycin-resistant Streptococcus pneumoniae. PMID- 2904566 TI - Cosmetic surgery: greater duty to warn of risks. PMID- 2904567 TI - Training courses for HIV/AIDS counsellors. PMID- 2904569 TI - Variation of apolipoprotein-B gene is associated with obesity, high blood cholesterol levels, and increased risk of coronary heart disease. AB - A random sample of 290 white men was examined for association between restriction fragment length polymorphism (RFLP) haplotypes (closely linked RFLPs on a single chromosome) of the apolipoprotein-B gene and serum levels of cholesterol, triglyceride, and high-density lipoprotein, obesity, smoking, alcohol consumption, and coronary heart disease. Haplotype or single RFLP frequencies differed significantly for obesity (p less than 0.005), serum cholesterol (p less than 0.005), and coronary heart disease (p less than 0.05), but for no other variable. Obesity was associated with haplotypes involving minimum PvuII and XbaI RFLPs are likely to be in linkage disequilibrium with nearby functional variation predisposing to obesity. Significant variation in serum cholesterol levels was associated with three functional alleles defined by MspI and EcoRI RFLP pairs (p less than 0.03). These RFLPs correspond to charged aminoacid variants at positions 3611 (arginine to glutamine) and 4154 (glutamic acid to lysine), which lie near the low-density-lipoprotein (LDL) receptor binding region of apolipoprotein-B. The three alleles showed stratification of serum cholesterol between low, normal, and high levels. Coronary heart disease was associated with minimum haplotypes involving XbaI and MspI RFLPs. Together these results suggest that inherited variations of the apolipoprotein-B gene, probably in the form of charged aminoacid substitutions, influence circulating cholesterol concentration, and that these and other functional variants of the apolipoprotein-B gene affect susceptibility to coronary heart disease and obesity. PMID- 2904568 TI - Prospective double-blind trial of duodenal ulcer relapse after eradication of Campylobacter pylori. AB - 100 consecutive patients with both duodenal ulcer and Campylobacter pylori infection were followed up to see whether eradication of C pylori affected ulcer healing or relapse. Patients were randomly assigned to 8 weeks of treatment with cimetidine or colloidal bismuth subcitrate (CBS), with tinidazole or placebo being given concurrently from days 1 to 10, inclusive. Endoscopy, biopsy, and culture were done at entry, in weeks 10, 22, 34, and 62, and whenever symptoms recurred. There was no maintenance therapy. C pylori persisted in all of the cimetidine-treated patients and in 95% of those treated with cimetidine/tinidazole, but was eradicated in 27% of the CBS/placebo group and 70% of the CBS/tinidazole group. When C pylori persisted, 61% of duodenal ulcers healed and 84% relapsed. When C pylori was cleared 92% of ulcers healed (p less than 0.001) and only 21% relapsed during the 12 month follow-up period (p less than 0.0001). PMID- 2904570 TI - Photochemical decontamination of blood components containing hepatitis B and non A, non-B virus. AB - Diluted plasma samples containing 10(2), 10(3), 10(4), and 10(5) chimpanzee infectious doses (CID) of a human non-A, non-B hepatitis virus (NANBV) were treated with a combination of two psoralen compounds, 4'-aminomethyl-4,5',8 trimethylpsoralen and 4,5',8-trimethylpsoralen, and exposed to long wavelength ultraviolet. Each dilution was then transfused into one of four chimpanzees. In a second experiment, three samples containing 10(4.5) CID of hepatitis B virus (HBV) and two samples containing 10(4) CID of NANBV were treated with 8 methoxypsoralen (8-MOP) and ultraviolet irradiation. Two chimpanzees were each transfused with both a treated HBV and a treated NANBV sample. The third chimpanzee was inoculated with a treated HBV sample alone. In the six months after inoculation none of the animals showed biochemical or histological evidence of hepatitis. In experiments involving NANBV inocula, the susceptibility of the animals was confirmed by subsequent challenge with untreated NANBV. Factor VIII concentrate containing virus and photochemically treated as in the first experiment retained an average of 91% of its activity while that in the second experiment retained 94% of its activity. PMID- 2904571 TI - Role of subcutaneous apomorphine in parkinsonian voiding dysfunction. AB - Ten patients with Parkinson's disease and urinary symptoms underwent urodynamic assessments before and after subcutaneous administration of the dopamine receptor agonist apomorphine. Voiding efficiency improved after apomorphine injection, with an increase in mean and maximum flow rates in nine patients and reduction in post-micturition residual volume in six. Although the effect on detrusor behaviour was variable, subcutaneous apomorphine may be of use in both the assessment and treatment of voiding dysfunction in patients with Parkinson's disease. PMID- 2904572 TI - Caffeinated beverages and decreased fertility. AB - 104 healthy women who had been attempting to become pregnant for three months were interviewed about their use of caffeinated beverages, alcohol, and cigarettes. In their subsequent cycles, women who consumed more than the equivalent of one cup of coffee per day were half as likely to become pregnant, per cycle, as women who drank less. A dose-response effect was present. PMID- 2904573 TI - Immunocytochemistry of neurofibrillary tangles in dementia pugilistica and Alzheimer's disease: evidence for common genesis. AB - A battery of antisera that specifically stained the tangles of Alzheimer's disease also stained the tangles in all of 8 cases of dementia pugilistica (punch drunk syndrome). Since the paired helical filament antigens found in Alzheimer type neurofibrillary degeneration are present in the tangles of dementia pugilistica the pathogenesis of tangle formation in these conditions is likely to be the same; thus head injury may be a predisposing factor or environmental trigger for Alzheimer's disease. PMID- 2904574 TI - Treatment of narcolepsy with L-tyrosine. AB - 8 patients with narcolepsy were treated with oral tyrosine. Within six months all were free from daytime sleep attacks and cataplexy. PMID- 2904575 TI - Coronary artery disease in hypertension. PMID- 2904576 TI - Mr Ridley's sewers. PMID- 2904577 TI - Complement activation in plasma exchange. PMID- 2904578 TI - Chronic liver disease and haemophilia. PMID- 2904579 TI - Complications of anaesthesia in infants and children. PMID- 2904580 TI - Duodenal ulcer, Campylobacter pylori, and the "leaking roof" concept. PMID- 2904581 TI - Effect of information campaign by the mass media on hysterectomy rates. AB - The annual frequency of hysterectomy was monitored in the Canton Ticino, Switzerland, from 1977 to 1986. From February to October, 1984, there was a public information campaign in the mass media about rates of and need for hysterectomy. After the start of the campaign and during the following year the annual rate of operations per 100,000 women of all ages dropped by 25.8%, whereas in the reference area (Canton Bern), where no information was given to the public, hysterectomy rates increased by 1%. In the same period the hysterectomy rate per 100,000 women aged 35-49 declined by 33.2%, and the number of hysterectomies performed annually per gynaecologist decreased by 33.3%. In Canton Bern these rates were unchanged. The decline began 2 months after the start of the information campaign. The reduction in the number of hysterectomies was greater (p less than 0.001) in non-teaching hospitals (31.9%) than in teaching hospitals (18.1%). Information on regional rates and on the need for hysterectomy given through the mass media to the general population can change professional practices. PMID- 2904582 TI - Clinical trial of intensive muscle training for chronic low back pain. AB - 105 patients who had chronic low back pain without clinical signs of lumbar nerve root compression or radiological evidence of spondylolysis or osteomalacia were randomised to three treatments: 30 sessions of intensive dynamic back extensor exercises over three months; a similar programme at one-fifth the exercise intensity; or one month of thermotherapy, massage, and mild exercises. The results consistently favoured intensive exercise, which had no adverse effects. Since these exercises can be conducted in groups, the intensive programme is no more costly than conventional strategies that require individual attention. PMID- 2904583 TI - Need for albumin adjustments of urgent total serum calcium. AB - In specimens sent for urgent total calcium measurement, failure to adjust for serum albumin concentration led to errors of diagnosis and treatment. Albumin adjustment is necessary, when measuring total serum calcium, for assessment of true calcium status. PMID- 2904584 TI - Cosmas and Damian, patron saints of doctors. PMID- 2904585 TI - Glucose tolerance in pregnancy. PMID- 2904586 TI - Insulin changeover. PMID- 2904587 TI - Fetal dopamine-rich mesencephalic grafts in Parkinson's disease. PMID- 2904588 TI - Waterborne outbreak of cryptosporidiosis. PMID- 2904589 TI - Misoprostol and ulcer prophylaxis. PMID- 2904590 TI - Motoneuron disease and past poliomyelitis. PMID- 2904591 TI - Outbreak of Dengue fever in Delhi. PMID- 2904592 TI - Clinical isolates of Vibrio cholerae O1 not producing cholera toxin. PMID- 2904593 TI - Platelet-activating factor. PMID- 2904594 TI - Breastfeeding and transmission of HIV. PMID- 2904595 TI - Low condom breakage rate in commercial sex. PMID- 2904596 TI - Bronchial bleeding with nebulised pentamidine. PMID- 2904597 TI - AIDS and neuroleptic malignant syndrome. PMID- 2904598 TI - Aspirin and myocardial infarction. PMID- 2904599 TI - Congenital hypothyroidism and growth hormone deficiency. PMID- 2904600 TI - Intrafallopian egg replacement without IVF back-up. PMID- 2904601 TI - Lessons from nomifensine. PMID- 2904602 TI - ACE inhibitors. PMID- 2904603 TI - Unethical trials of dipyrone in Thailand. PMID- 2904604 TI - Medical care for the newborn. PMID- 2904605 TI - London Hospital helicopter emergency medical service. PMID- 2904606 TI - Computers, epidemiology, and general practice. PMID- 2904607 TI - Academic boycotts and South Africa. PMID- 2904608 TI - Cancer risk estimate for radiation, 1988. PMID- 2904609 TI - Energy needs of infants. PMID- 2904610 TI - Physicians and peace prospects. PMID- 2904611 TI - Intraperitoneal erythropoietin. PMID- 2904612 TI - Urology and the TNM classification. PMID- 2904613 TI - Vascular access for chronic haemodialysis. PMID- 2904614 TI - Treatment of systemic capillary leak syndrome. PMID- 2904615 TI - Endothelin and cyclosporin nephrotoxicity. PMID- 2904617 TI - Phosphorus-32, an unexpected treatment for rheumatoid arthritis. PMID- 2904616 TI - Moles in Australian and British school children. PMID- 2904618 TI - Hyperphenylalanaemia in parenterally fed newborn infants. PMID- 2904620 TI - Of pancreas, pain, and papilla. PMID- 2904619 TI - Acute hepatitis after treatment of acromegaly with octreotide. PMID- 2904621 TI - Thrombolysis "update". PMID- 2904622 TI - Neuroleptic malignant-like syndrome and lithium. PMID- 2904623 TI - Glove perforation during sternotomy closure. PMID- 2904624 TI - Neuroleptic malignant syndrome after clozapine plus carbamazepine. PMID- 2904625 TI - Cardiopulmonary resuscitation in cases of malignant disease. PMID- 2904626 TI - Thromboembolism and air travel. PMID- 2904627 TI - Ganciclovir for severe cytomegalovirus infection in transplant recipients. PMID- 2904628 TI - Campylobacter gastritis and vomiting. PMID- 2904629 TI - Hypovitaminosis A of follicular duct as cause of acne vulgaris. PMID- 2904630 TI - A psychiatrist's duty of confidentiality. PMID- 2904631 TI - Small-cell lung cancer after retinoblastoma. PMID- 2904632 TI - Back calculation of alcohol: the "hip-flask defence". PMID- 2904633 TI - Interaction between clozapine and a lipophilic alpha 1-adrenergic agonist. AB - Acute intraperitoneal injection of clozapine produced marked hypothermia and ataxia in Swiss-Webster mice. These two effects were almost completely blocked by the lipophilic alpha 1-adrenergic agonist, St 587, but not by the peripherally acting alpha 1 agonist methoxamine. It was inferred that these effects of clozapine are central in origin and probably resulted from alpha 1 adrenergic blockade. However, since prazosin, a selective alpha 1-adrenergic antagonist did not elicit either hypothermia or ataxia in mice it became clear that the alpha 1 adrenergic blocking effect of clozapine is not entirely responsible for these effects, but has a major contributory role in their production. Both clozapine and prazosin inhibited the d-amphetamine-induced locomotor stimulation in mice. St 587 did not significantly reduce this amphetamine-blocking effect of clozapine. It was inferred that this response to d-amphetamine involving the release of mesolimbic dopamine is distinct from the other two St 587-sensitive responses. The hypothermic and ataxic effects of clozapine developed complete tolerance after just four days of treatment, but ten days of such treatment was required for the development of tolerance to the amphetamine-blocking effect of clozapine. The possible relationships between St 587-sensitive and insensitive effects of clozapine and its antipsychotic property are discussed. PMID- 2904634 TI - Specific [3H]UK 14,304 binding in human cortex occurs at multiple high affinity states with alpha 2-adrenergic selectivity and differing affinities for GTP. AB - [3H]UK 14,034 is a full agonist at alpha 2-adrenergic receptors. Although the characteristics of the binding of the partial alpha 2-adrenergic agonists in postmortem human brain were known, the binding of [3H]UK 14,304 had not been studied in this tissue. Multi-site binding of this radiolabel had been reported in other tissues and guanosine triphosphate (GTP) had been shown to reduce [3H]UK 14,304 binding. We now report that [3H]UK 14,304 labels at least 2 specific binding sites in human brain that both have the characteristics of an alpha 2 adrenergic binding site. GTP decreases agonist binding at both of these sites, but with different potencies at each site. PMID- 2904635 TI - Serotonergic component of SCH 23390: in vitro and in vivo binding analyses. AB - A series of benzazepines related to SCH 23390 were tested for binding to the 5HT 2 receptor. The compounds tested inhibited the binding of 3H-ketanserin with KI values generally greater than those observed for the D-1 receptor, but less than those for the D-2 receptor. When this serotonergic activity was correlated to the D-1 activity, the resulting coefficient was 0.84, indicating a strong correlation between the two activities. Conversely, the 5HT-2 activity did not show a good correlation with the D-2 activity. To further test the significance of the 5HT-2 binding of the SCH 23390, in vivo binding studies were performed using 125I-SCH 38840 in the frontal cortex, an area containing both D-1 and 5HT-2 receptors. The in vivo binding of 125I-SCH 38840 to frontal cortex exhibited peak levels one hour following subcutaneous administration, similar to the time course previously observed in striatum. The binding was both D-1 and tissue specific. Competition studies with selected standards demonstrated that inhibition of the binding to frontal cortex, in contrast to the inhibition observed in the striatum, exhibited a Hill coefficient less than unity, implying interaction at more than one receptor subtype. When SCH 23390 and ketanserin were administered simultaneously, the inhibition of the in vivo binding of 125I-SCH 38840 to striatum was not different than that observed with SCH 23390, alone. However, the inhibition of binding to frontal cortex was significantly greater than that demonstrated with either SCH 23390 or ketanserin, alone, suggesting that 125I-SCH 38840 was binding to both D-1 and 5HT-2 receptors, in vivo. PMID- 2904636 TI - Docosahexaenoic acid and other dietary polyunsaturated fatty acids suppress leukotriene synthesis by mouse peritoneal macrophages. AB - The efficacy of individual omega-3 polyunsaturated fatty acids (PUFA) in altering eicosanoid synthesis in peritoneal macrophages was studied by feeding mice for 10 days a diet containing 2 wt % fat, which included 0.5 wt % ethyl esters of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) or linolenic acid (LNA). Upon stimulation with calcium ionophore A23187, macrophages from these animals produced significantly lower amounts of leukotriene C4, leukotriene B4 and 12 hydroxyeicosatetraenoic acid, prostaglandin E2 and 6-keto prostaglandin F1 alpha compared with those obtained from animals on the diets containing olive oil or safflower oil. The decrease in leukotriene synthesis was similar in the animals fed DHA, EPA or LNA diets. This depression of eicosanoids by DHA and EPA was associated with decreased levels of arachidonic acid (AA); however, LA that altered eicosanoids did not have the same effect on AA levels. PMID- 2904637 TI - The O75X adhesin of uropathogenic Escherichia coli: receptor-active domains in the canine urinary tract and in-vitro interaction with laminin. AB - The complementary binding sites for the purified O75X adhesin of uropathogenic Escherichia coli in canine urinary tract were determined by indirect immunofluorescence. The adhesin bound to the vascular basement membranes in the canine kidney, ureter, bladder and urethra. In the kidney, the adhesin bound also to the tubular basement membranes and to the Bowman's capsule and mesangium of the glomeruli. In the bladder and ureter, but not in the urethra, the O75X adhesin bound to the basal lamina of smooth muscle cells. Connective tissue was negative for the adhesin. Interestingly, considerable intraepithelial heterogeneity was revealed as the O75X adhesin bound to epithelium of the ureter but not to that of the kidney, bladder or urethra. The purified O75X adhesin bound specifically to laminin, a basement membrane glycoprotein, immobilized on nitrocellulose or polystyrene, suggesting that laminin is involved in the binding of the O75X adhesin to basement membranes. PMID- 2904638 TI - Characterization of fimbriae from Bacteroides fragilis. AB - Fimbriae derived from Bacteroides fragilis strain BE1 (BE1 fimbriae) appeared to be composed of subunits with a molecular weight of 40,000. Under the electron microscope the fimbriae could be visualized as straight filaments with a diameter of 4 nm. It appeared that production of the BE1 fimbriae is repressed under conditions of iron limitation, and at a growth temperature of 20 degrees C. Antibodies raised against the 40,000 dalton polypeptide, purified by means of preparative SDS-polyacrylamide gelelectrophoresis, recognized the native fimbriae, as was shown by immunogold labelling of intact bacterial cells, and by immunoprecipitation. Immunoblot experiments showed that other strains of B fragilis tested produced polypeptides, ranging in molecular weight from 40,000 to 42,000, that are antigenically related to the BE1 fimbrial subunit. No haemagglutination activity could be associated with the BE1 fimbriae. PMID- 2904639 TI - Nucleotide sequence analysis of a P fimbrial regulatory element of the uropathogenic Escherichia coli strain KS71 (04:K12). AB - The nucleotide sequence of a trans-acting P-fimbrial regulatory element obtained from the uropathogenic Escherichia coli strain KS71 (04:K12) was determined. The regulatory element was found to contain an open reading frame of 231 nucleotide residues that showed 95.2% homology with papl, a functionally analogous regulatory gene of E. coli strain J 96. PMID- 2904640 TI - Expression and secretion of pertussis toxin subunit S1 in Bacillus subtilis. AB - Pertussis toxin (PT) is an important virulence determinant of Bordetella pertussis and one of the major protective antigens against whooping cough. The genes coding for PT have recently been cloned, but attempts to express them in Escherichia coli have been unsuccessful. We therefore explored the possibility of expressing these genes in Bacilius subtilis for which efficient vectors are available. The lack of endotoxin in the Gram-positive Bacillus might be an additional advantage for the production of a vaccine component. A DNA fragment coding for S1, one of the subunits of pertussis toxin, was inserted into an alpha amylase secretion vector and the recombinant plasmid was introduced into B. subtilis. This resulted in high expression of S1, most of which was secreted and therefore found in the culture supernatant. This supernatant had ADP-ribosylating activity similar to that of PT. Western blot with antiserum to B. pertussis holotoxin showed several proteins ranging in size from 28 kDa to 20 kDa reacting in specific manner. About 10% of the protein recognized by the antiserum was of the size expected for native-size S1. The total amount of S1 proteins (full size and truncated) in the culture supernatant was about 100 mg/l. S1 protein made in B. subtilis was partially purified using chromatography with P-cellulose and Blue Sepharose. This preparation was used to immunize rabbits; the immune serum thus obtained recognized subunit S1 of native pertussis toxin. PMID- 2904641 TI - Carboxyl groups in Clostridium perfringens epsilon toxin. AB - The maximal number of norleucine methyl ester (NME) incorporated into carboxyl groups in epsilon toxin of Clostridium perfringens by the carbodiimide nucleophile procedure was 7 and 17 in the absence and presence of 8 M urea, respectively. The introduction of 3-4 nucleophilic modifying agents such as NME, glycine methyl ester or taurine into carboxyl groups of the toxin reduced the lethality to approximately 10% of the original activity. The incorporation of 6-7 of these agents resulted in complete loss of the activity. On the other hand, circular dichroism spectra and the reaction between the toxin or the NME incorporated toxin and antiepsilon toxin reaction showed no difference between the intact toxin and the NME-incorporated toxin. The data suggested that at least 4 out of 7 carboxyl groups on the surface of the toxin are important in maintaining the lethal activity of toxin. PMID- 2904642 TI - Morphological studies on fimbriae expressed by Vibrio cholerae 01. AB - Colonization of the small intestine is an essential step in the pathogenesis of Vibrio cholerae diarrhea. At least one type of fimbriae, known as TcpA are required for the colonization process. This paper reports electron microscopic evidence that V. cholerae strains can express at least two other fimbrial types. Classical strains express three types: TcpA fimbriae are 5-6 nm in diameter and form bundles of parallel undulating filaments up to 15 micron long; Type B are 3 nm wide and of wavy morphology, and Type C are rigid, isolated filaments 5-6 nm wide and 180-800 nm long. El Tor strains express fimbriae resembling Types B and C. Types B and C were also found on a tcpA- isogenic mutant of V. cholerae 395 N1, and are thus encoded by genetically distinct loci. TcpA fimbriae, but not Types B or C, were labeled with gold-conjugated anti-TcpA antibody. Four El Tor strains, including two environmental isolates that poorly colonize humans, expressed fimbriae resembling Types B and C, but did not express TcpA. Multiple types of fimbriae may represent colonization factors for surfaces present in the environment and in the human gut. Characterization of the role of fimbriae in immunogen presentation and immunity could facilitate the improvement of cholera vaccines. PMID- 2904643 TI - Purification of fimbriae from Pasteurella haemolytica A-1. AB - Pasteurella haemolytica A-1 produces large, rigid fimbriae with a diameter of 12 nm and a denisty of 1.32. Their subunit molecular weight was 35,000 as determined by SDS-polyacrylamide gel electrophoresis and immunoblotting with monoclonal antibodies raised against native fimbriae. The isoelectric point of the purified fimbriae was 4.8. While Pasteurella haemolytica whole cells plus a crude shear fraction were capable of agglutinating bovine erythrocytes, purified fimbriae exhibited no such activity. PMID- 2904644 TI - Bicycle-spoke and "doubling" injuries. AB - A "doubling" injury is the result of two persons, usually two children, but often an adult and a child, riding on a bicycle. The most-common variety is the "bicycle-spoke injury" which is sustained when the passenger's foot is caught in the spokes of the wheel. Between August 1, 1986 and July 31, 1987, 43 children (mean age, 55 months) attended the Emergency Department of Princess Margaret Hospital for Children with such an injury. None of the bicycles had spoke-guards. Sixteen children were admitted to hospital: eight children required skin grafts and four children required repair by sutures. Nineteen (44%) of the children had bare feet when they were injured. The healing time ranged from seven to 365 days with an average of 56 days, which was long enough to ruin a child's holiday. This injury can be prevented. "Doubling" is dangerous and should be prohibited where seats and spoke-guards are not available. The attention of parents and the community should be drawn to the potentially-serious nature of these injuries. PMID- 2904645 TI - Healing our planet: a global prescription. PMID- 2904646 TI - Acute regional vascular insufficiency after jellyfish envenomation. AB - Three cases of jellyfish envenomation which occurred in the Indian Ocean and the Andaman Sea are reported. In each instance the stinging occurred on the upper extremities, and impaired the circulation to the stung limb(s), with absent distal arterial pulses, regional cyanosis, and the threat of distal gangrene. One of the patients is seriously and permanently handicapped, with bilateral upper limb numbness and paresis; another patient has permanent sensory loss; the third patient, who also had brachial-artery narrowing that was demonstrated by angiography, made an uneventful recovery. The first two patients underwent surgical fasciotomy, whereas surgical exploration was performed on the third patient. Reduced blood flow in the major arteries of the limbs was observed directly in each case. Further, the arterial segment that primarily was affected, in each case, appeared to be that which underlay the actual site of the sting. All patients were young persons with no previous history of vascular disease. These cases corroborate the vascular and neurogenic injury, which previously have been reported in experimental animals and in human patients, that may result from jellyfish venoms. PMID- 2904647 TI - Inhibition of adenylate cyclase is mediated by the high affinity conformation of the alpha 2-adrenergic receptor. AB - The functional significance of high affinity agonist binding to receptors that interact with guanine nucleotide regulatory proteins has remained controversial. Preincubation of human platelet membranes with the full alpha 2-agonist UK 14,304 in the absence of GTP increases the potency of the agonist to inhibit adenylate cyclase in a pre-steady state (15-sec) assay. The EC50 after preincubation (6 +/- 1 nM) is within a factor of 2 of the high affinity Kd for [3H]UK 14,304 binding determined under identical conditions (2.7 +/- 0.1 nM). In contrast, in the usual steady state measurements (15 min) or in pre-steady state measurements without agonist preincubation, the EC50 values (74 +/- 1 and 207 +/- 8 nM, respectively) are near the low affinity Kd for [3H]UK 14,304 binding. Reduction of the GTP concentration in steady state adenylate cyclase assays also decreases the EC50 for UK 14,304 from 40 +/- 5 nM at 10 microM GTP to 14 +/- 5 nM with no added GTP. Both sets of experimental observations are accommodated by a complete kinetic model of inhibition in which the high affinity ternary complex of drug, receptor, and G protein leads to the response. Explicit rate parameters are included for agonist binding, receptor-G protein interactions, GTP binding, and hydrolysis. Despite the functional role of the high affinity state of the alpha 2-receptor in this model, the steady state EC50 for agonist-mediated inhibition correlates best with the Kd of low affinity agonist binding in the presence of high levels of GTP. Under conditions in which formation of the high affinity ternary complex is favored, the EC50 for responses approaches the high affinity Kd. PMID- 2904648 TI - Continuous intracerebroventricular infusion of dopamine and dopamine agonists through a totally implanted drug delivery system in animal models of Parkinson's disease. AB - We studied the effect of intracerebroventricular infusion of dopamine and dopamine agonists in rat and primate models of Parkinson's disease as an experimental approach to the treatment of levodopa-induced fluctuations. The infusion of dopamine, lisuride, and pergolide into the ventricle ipsilateral to the lesion, by 6-hydroxydopamine, of the nigrostriatal pathway induced a contralateral rotation which was maximal 24-48 h after infusion and whose intensity progressively decreased over the period of 1 week. [3H]Spiperone binding was decreased by the infusion of dopamine but the responses to subcutaneous apomomorphine were unchanged. The infusion of dopamine also restored the levels of monoamines in the rat brain. In chronic reserpized rats, the infusion of dopamine restored brain levels of dopamine but did not reverse akinesia unless monoamine oxidase inhibitors were simultaneously administered, either systemically or intracerebroventricularly. Lisuride and pergolide proved much weaker than dopamine in reversing the effects of reserpine. Intracerebroventricular infusion of dopamine plus deprenyl reversed MPTP induced akinesia in monkeys but the pump used for the delivery was not well tolerated, because of its size, by the animals. PMID- 2904649 TI - PHNO, a novel dopamine agonist, in animal models of parkinsonism. AB - PHNO, a naphthoxazine compound, was investigated in animal models of central dopaminergic activity. The drug in doses of 5-300 micrograms/kg when administered subcutaneously, or transdermally, induced stereotypic behavior in rats which was blocked by haloperidol but not by reserpine pretreatment. In rats with unilateral 6-hydroxydopamine lesions of the substantia nigra PHNO induced dose-dependent contralateral turnings. The drug caused emesis in dogs and hypothermia in mice. PHNO bound to D-2 dopamine receptors in the rat striatum. Chronic injection with PHNO did not induce behavioral supersensitivity or increase dopamine receptor density. These data indicate that PHNO is a direct acting dopamine agonist that is highly potent. PHNO differs from other dopaminergic drugs and may be useful in the treatment of Parkinson's disease. PMID- 2904650 TI - The effect of intracerebroventricular infusion of (+)-4-propyl-9 hydroxynapthoxacine (PHNO) through a totally implanted drug delivery system in rats with dopamine deficiency. AB - Rats with experimentally induced DA deficiency were treated with intracerebroventricular administration of (+)-4-propyl-9-hydroxynaphthoxacine (PHNO) through a totally implanted chronic delivery system which delivered PHNO, 0.9 microgram/h, continuously for up to 2 weeks. Rats with 6-OH-DA induced unilateral nigrostriatal lesion showed, after PHNO infusion, a potent and persistent contralateral turning behavior (8-11 turns/min) which was not present in vehicle-infused animals. The intensity of spontaneous and apomorphine-induced rotation did not decrease after 2 weeks of continuous infusion, suggesting that tolerance to PHNO or to other dopamine agonists did not develop. The magnitude of the spontaneous turning behavior in PHNO-infused animals correlated well with the baseline response to apomorphine (r = 0.505, p less than 0.025). Rats implanted with pumps delivering PHNO or vehicle were treated with reserpine, 0.5 mg/kg/day for 14 days. Vehicle-infused, reserpinized animals had a severe akinesia and weight loss during the experimental period (motor activity, measured in counts per minute was reduced to 5-10% of baseline levels, and body weight to 50% of baseline levels). PHNO-infusion partially restored activity to 60% of baseline counts and reduced the severity of weight loss. PHNO effects were observed for as long as the infusion was maintained. No side effects were observed. Intracerebroventricular infusion of PHNO may be an alternative experimental approach to untreatable motor fluctuations in Parkinson's disease. PMID- 2904651 TI - Cushing's syndrome due to ectopic ACTH secretion by bilateral pheochromocytomas in multiple endocrine neoplasia type 2A. PMID- 2904652 TI - Homoeo boxes, POU proteins and the limits to promiscuity. PMID- 2904653 TI - A cloned octamer transcription factor stimulates transcription from lymphoid specific promoters in non-B cells. AB - The complementary DNA coding for a lymphocyte-specific transcription factor binding to the DNA 'octamer' sequence TNATTTGCAT has been cloned. The nucleotide sequence shows homology to the homoeobox domain. Expression of this cDNA in HeLa cells is sufficient for a strong transcriptional activation of B-cell-specific promoters. PMID- 2904654 TI - A human lymphoid-specific transcription factor that activates immunoglobulin genes is a homoeobox protein. AB - The human lymphoid-specific transcription factor OTF-2 contains a homoeodomain that is required for DNA binding and binds specifically to DNA elements that are recognized by Drosophila homoeodomain proteins, suggesting coevolutionary relationships between mammalian and invertebrate homoeodomain proteins and their DNA recognition elements. PMID- 2904655 TI - Drosophila homoeotic genes encode transcriptional activators similar to mammalian OTF-2. AB - Homoeotic genes in Drosophila melanogaster are active in spatially restricted metameric domains and control the morphogenesis of segment-specific features such as legs or wings within these domains. They exert their function, according to the 'selector gene' hypothesis, by regulating the expression of subordinate genes. Homoeotic genes also control their own expression and the expression of each other. The proteins encoded by these genes contain a domain, called a homoeodomain, that is strongly conserved, and that shows homologies to proteins that bind DNA and regulate transcription. Homoeoproteins have been shown to bind specific DNA sequences. We show here that the Drosophila homoeotic genes Ultrabithorax (Ubx) and Abdominal-B (Abd-B) code for proteins that are capable of activating transcription of reporter genes linked to specific cis-regulatory target sequences in transfected mammalian cells. Their activity, as well as their target specificity, is similar to that of a mammalian lymphoid-specific octamer transcription factor, OTF-2, which was recently found to contain a homoeodomain. PMID- 2904656 TI - The POU domain is a bipartite DNA-binding structure. AB - The POU domain (pronounced 'pow') is a highly charged 155-162-amino-acid (aa) region of sequence similarity contained within three mammalian transcription factors. Pt-1 (ref. 2), Oct-1 (ref. 3) and Oct-2 (ref. 4), and the product of the nematode gene unc-86 (ref. 5) which is involved in determining neural cell lineage. This domain consists of two subdomains, a C-terminal homoeo domain and an N-terminal POU-specific region separated by a short nonconserved linker; the sequence relationship shows that the POU homoeo domains form a distinct POU related family. In the ubiquitous and lymphoid-specific octamer-motif binding proteins Oct-1 and Oct-2, the POU domain is sufficient for sequence-specific DNA binding. Homoeobox domains contain a helix-turn-helix DNA-binding motif, first identified in bacterial repressors. The helix-turn-helix region of the POU domain is important for DNA binding and, in other classes of homoeo-containing proteins, the entire homoeo domain is sufficient for DNA binding; thus the new POU-specific region could be involved in other functions such as protein-protein interactions. Nevertheless, we show here that in fact the POU domain is a novel bipartite DNA binding structure in which the POU homoeo and POU-specific regions form two subdomains that are both required for DNA binding but are held together by a flexible linker. PMID- 2904657 TI - Conservation of the D-mannose-adhesion protein among type 1 fimbriated members of the family Enterobacteriaceae. AB - A variety of genera and species of the family Enterobacteriaceae bear surface fimbriae that enable them to bind to D-mannose residues on eukaryotic cells. Until recently, it was thought that the D-mannose binding site was located in the major structural subunit (FimA), of relative molecular mass (Mr) 17,000 (17 K), of these organelles in Escherichia coli. New evidence indicates that this binding site resides instead in a minor protein Mr 28-31 K (FimH) located at the tips and at long intervals along the length of the fimbriae, and is reminiscent of the minor tip adhesion proteins of pyelonephritis-associated pili (Pap) and S fimbriae. In contrast to the antigenic heterogeneity of the major FimA subunit, the antigenic structure of FimH is conserved among different strains of E. coli. Here, we report an even broader conservation of this minor adhesion protein extending to other genera and species of type 1 fimbriated Enterobacteriaceae. Our results may have implications for the development of broadly protective vaccines against Gram-negative bacillary infections in animals and perhaps in man. PMID- 2904658 TI - Fair dinkum koala kuisine--eucalyptus oil poisoning. PMID- 2904659 TI - [Effect of antagonists of excitatory amino acids on synaptic transmission in the electroreceptors (Lorenzini's ampullae) in skates]. AB - Ampullae of Lorenzini isolated from the skate (Raja clavata) have been investigated in vitro electrophysiologically to determine the nature of the transmitter at the synapse between the electroreceptor cells and afferent fibres. Glutamic acid diethyl ester (GDEE), glutamic acid dimethyl ester (GDME), kynurenic acid (KENYA), cis-2,3-piperidine dicarboxylic acid (PDA) reversibly decreased the resting and stimulus-induced activity. These antagonists also blocked postsynaptic responses induced by glutamate and aspartate. D-alpha aminoadipic acid (DAA) had no effect on the afferent activity. These findings suggest that glutamate, aspartate or a related compound may be a transmitter at this synapse. An important physiological role of quisqualate receptors in ampullae of Lorenzini is also inferred from these experiments. PMID- 2904660 TI - Effects of piracetam on single central neurons. AB - Piracetam, when applied microiontophoretically and/or by hydropneumatic pump on the somatosensory cortex and hippocampus of the rat, affected neuronal activity by depressing or facilitating the spontaneous firing rate, depending on the area studied. Its effect were either additive or counteracting the actions of glutamate, gamma-aminobutyric acid and acetylcholine, when administered together on the same neuron, thus supporting the assumption that its action is directed towards specific membrane elements, presumably the synaptic sites. PMID- 2904661 TI - Neurotransmitter systems and personality measurements: a study in psychosomatic patients and healthy subjects. AB - A comparative study performed in psychosomatic patients (PG) and healthy subjects (HG) reveals several correlations between personality measurements (Minnesota Multiphasic Personality Inventory, Sensation Seeking Scale, Susceptibility to Punishment), and biochemical variables (in serum: MHPG, acetylcholinesterase, calcium, melatonin; and in platelets: monoamine oxidase B, serotonin, calcium proteins). The relationship between some Sensation Seeking subscales and the enzymatic activities evaluated (negative with MAO and positive with AChase) and the opposite sign relationship between serotonin and some scales of MMPI in both groups studied (negative in the PG and positive in the HG) are noteworthy. PMID- 2904662 TI - Topographic immunocytochemical mapping of monoamine oxidase-A, monoamine oxidase B and tyrosine hydroxylase in human post mortem brain stem. AB - Immunocytochemical demonstration of monoamine oxidase-A, monoamine oxidase-B and tyrosine hydroxylase was performed in the human brain stem using monoclonal antibodies to monoamine oxidase-A and monoamine oxidase-B and polyclonal antibodies to tyrosine hydroxylase. In most of the brain areas examined, except the serotonergic dorsal nucleus of raphe, the noradrenergic locus coeruleus and the dorsal efferent nucleus of vagus, tyrosine hydroxylase-positive neurons were in greater number than monoamine oxidase-A-stained or monoamine oxidase-B-stained neurons. The dorsal nucleus of raphe showed no tyrosine hydroxylase immunoreactivity, but reacted positively to serotonin- and monoamine oxidase-B antibodies, while monoamine oxidase-A staining was moderate. In none of the investigated brain areas did neurons exclusively react with monoamine oxidase-B antibodies without expressing monoamine oxidase-A in a few neurons, while in some areas neurons expressed both monoamine oxidase-A and tyrosine hydroxylase (locus coeruleus; dorsal efferent nucleus of vagus). The oculomotor nucleus stained only with monoamine oxidase-A antibodies, substantia nigra neurons reacted only with tyrosine hydroxylase antibodies. Glial staining in most of the brain areas examined seemed, with slight differences, to have the same intensity with monoamine oxidase-A and monoamine oxidase-B antibodies used. No glial staining was obtained with tyrosine hydroxylase antibodies. PMID- 2904663 TI - Endogenous dopamine and dopaminergic agonists modulate synaptic excitation in neostriatum: intracellular studies from naive and catecholamine-depleted rats. AB - Intracellular recordings from slices of rat neostriatum were utilized to study the effects of endogenous dopamine and of exogenous dopaminergic agonists on the excitatory synaptic potentials evoked by the local stimulation of the slice. D Amphetamine (0.1-5 microM), as well as dopamine, produced a dose-dependent decrease of the excitatory synaptic potentials. This effect was blocked by membrane hyperpolarization. The blockade of potassium channels by intracellular cesium or by extracellular 4-aminopyridine (0.5-1 mM) did not block the voltage dependent effect of dopamine. The effects of D-amphetamine were antagonized by (R)-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7 -ol (SCH 23390) (0.1-1 microM), an antagonist for D1 dopaminergic receptors, but not by sulpiride (0.1-1 microM), an antagonist for D2 receptors. Pretreatment of the animals with alpha-methyl-p-tyrosine (200 mg/kg) or with reserpine (5 mg/kg) blocked the amphetamine-induced effect on the synaptic potentials. In reserpinized animals, the hyperpolarization of the membrane potential did not block the dopamine-induced decrease of the synaptic excitation. After reserpine pretreatment bromocryptine and lysuride, D2 agonists which in control conditions were ineffective, also mimicked the effects of dopamine. In reserpinized rats, the inhibitory effects of the dopaminergic agonists were antagonized by sulpiride, but not by SCH 23390. We conclude that in naive animals endogenous dopamine mimics the voltage-dependent reduction of synaptic excitation produced by D1 activation, while in catecholamine-depleted rats dopamine lacks its voltage dependent effect and interacts with "supersensitive" D2 receptors. PMID- 2904664 TI - Ca2+-dependent and Ca2+-independent glutamate release, energy status and cytosolic free Ca2+ concentration in isolated nerve terminals following metabolic inhibition: possible relevance to hypoglycaemia and anoxia. AB - Hypoglycaemia and anoxia both cause massive release of glutamate from the brain in vivo, and the nature of this release was investigated using guinea-pig cerebral-cortical synaptosomes and iodoacetate and rotenone to simulate the energetic consequences of these conditions. Glutamate release (by continuous fluorimetry), cytoplasmic free Ca2+ (by fura-2), membrane potentials, ATP, ADP and creatine phosphate were determined in parallel, following the addition of iodoacetate or rotenone, alone or in combination. Ca2+-dependent glutamate release had a high energy requirement which could only be satisfied by aerobic glycolysis. Respiration using endogenous substrates, or anaerobic glycolysis following rotenone, caused a progressive inhibition of Ca2+-dependent release, correlating with a decline in the total ATP/ADP ratio and creatine phosphate. With rotenone, an increase in Ca2+-independent glutamate release was observed, correlating with a decline in plasma membrane potential. Only a slight increase in free Ca2+ was seen. Rotenone plus iodoacetate caused an almost immediate collapse of ATP/ADP ratio and a parallel loss of Ca2+-dependent glutamate release before free Ca2+ had risen to a level sufficient for exocytosis. In contrast, Ca2+-independent glutamate release increased. The Ca2+-dependent release of L glutamate had the characteristics of an exocytotic transmitter release mechanism, being energy-dependent and triggered by elevated cytoplasmic free Ca2+ concentration. A distinct Ca2+-independent release of cytoplasmic glutamate occurred by reversal of the Na+-coupled uptake carrier, which was accelerated by a decline in the Na+ gradient. It is concluded that the Ca2+-independent release of cytoplasmic glutamate may make the major contribution to the excitotoxic release of glutamate in hypoglycaemic and anoxic conditions. PMID- 2904665 TI - Synapse-competence of LA-N-2 human neuroblastoma cells in coculture with rat striated muscle cells. AB - The purpose of this study was to determine whether cells of the human neuroblastoma line, LA-N-2, are capable of establishing functional synapses in culture. We used a coculture system in which striated muscle cells from the rat served as postsynaptic targets for the cholinergic LA-N-2 cells. By recording postsynaptic responses from muscle cells, differentiated LA-N-2 cells were found to innervate muscle cells, releasing acetylcholine spontaneously at LA-N-2-muscle synapses. A subpopulation of the LA-N-2 cells forming synapses with the muscle cells also developed the ability to release acetylcholine in response to stimulation. This, coupled with results obtained from experiments examining the time course of synapse formation, led us to propose that the extent to which LA-N 2 cells in our coculture system are differentiated may vary and that this variation may underlie the degree to which they express neuron-like transmission properties. PMID- 2904666 TI - [Clinical significance of urinary enzyme loss after extracorporeal circulation. Enzymuria is a predictive index of early renal damage]. PMID- 2904667 TI - [First aid and treatment of bites by snakes of the genus Vipera]. AB - The amount of injected snake venom, the seriousness of the poisoning, the local and general clinical manifestations are influenced by several causes, which are analysed here. The most recent discoveries suggest the tight binding the bitten limb, extending the bandages as high as possible and applying a splint to the limb, in the first aid. The main steps of treatment, the laboratory tests, which may help the physician to follow the course of the poisoning, are then reported. PMID- 2904668 TI - Neuropathological evaluation by combined immunohistochemistry and degeneration specific methods: application to methylenedioxymethamphetamine. AB - To best interpret the significance of neurological alterations produced by chemicals, the changes in morphological as well as neurochemical parameters must be measured and compared to each other. We have devised an approach to readily label microscopic sections for multiple antigens (neurotransmitters, enzymes, peptides, etc.) as well as for the demonstration of degenerating structures by silver impregnation. Here, we applied silver-staining together with immunolabelling of 5-HT and tyrosine hydroxylase (the rate-limiting enzyme for dopamine synthesis) to study neurohistological alterations produced by methylenedioxymethamphetamine (MDMA), a hallucinogenic stimulant previously used as an adjunct to psychotherapy and now a popular recreational drug ("Ecstasy"). Single oral doses of 40 or 80 mg/kg MDMA doubled the density of silver impregnated (degenerating) fiber terminals in the caudate nucleus compared to controls, when rats were sacrificed 18 hours after treatment. Four months after two 40 mg/kg oral doses per day for four days, rats had a reduced neurochemical content of 5-HT in the hippocampus, and fewer immunostainable 5-HT axons per unit area in the hippocampal stratum lacunosum but no change in brain-stem neurochemical 5-HT content or in the numeric density of 5-HT-positive cell bodies in the dorsal raphe nucleus. The neurohistology suggests interpreting the changes in neurochemical content of serotonin produced by MDMA as due to degeneration followed by subsequent loss of 5-HT axons, rather than a decrease in the rate of neuronal 5-HT synthesis or a toxicity directed toward 5-HT cell bodies. The combination of neurohistological and neurochemical evaluation will continue to prove useful in comprehensive evaluation of the neurological effects of chemical exposure. PMID- 2904669 TI - Neurochemical evaluation of rats prenatally exposed to the adrenergic agonists clonidine and lofexidine. AB - Clonidine (CLON), an alpha-2 adrenergic agonist, is widely used to reduce hypertension; it is also recommended for blocking acute opiate withdrawal. Lofexidine (LOF), a CLON analog, is an investigational compound being readied for the marketplace. Since exposure to both drugs is likely to occur in the last two trimesters of human pregnancy, it is important to determine whether such exposure can have effects upon brain or behavior of offspring. Pregnant CD rat dams were given daily subcutaneous injections of saline, CLON, or LOF on days 8 through 20 of gestation. Maternal weight during gestation, neonatal weight and neurochemical measures were monitored. Maternal body weight was reduced in a dose dependent manner. At PND 1 brain ornithine decarboxylase (ODC) activity was reduced in LOF- but not CLON-exposed pups of both sexes. At this age no alteration was seen in whole brain catecholamine levels or in whole brain alpha-2-adrenergic binding. PMID- 2904670 TI - [Preliminary study of the apical reactions following experimental trauma (of concussion type) on dog's immature teeth]. PMID- 2904671 TI - Distinguishable effects of intrathecal dynorphins, somatostatin, neurotensin and s-calcitonin on nociception and motor function in the rat. AB - We determined the effects on nociceptive threshold and motor function of dynorphin-gene products, dynorphin A-(1-32) (DYN A-(1-32), DYN A-(1-8), DYN B and DYN B-29 and the non-opioid peptides somatostatin, neurotensin and salmon calcitonin (s-CT) after intrathecal administration in the rat. DYN A-(1-32) (25 nmol) produced maximal elevation of tail-flick latency accompanied by severe hind limb paralysis and tail flaccidity lasting 6 h and still present at 24 h in several animals. Antinociception evaluated by the vocalization test wore off within 2 h. A lower dose of the peptide (6.25 nmol) did not alter the tail-flick reflex and motor function but significantly elevated the vocalization threshold. The other dynorphins showed weaker, short-lasting activity on the nociceptive threshold, the order of potency being as follows: DYN B-29 greater than DYN B greater than DYN A-(1-8). On the other hand, at the high doses DYN B (100 nmol) and DYN B-29 (50 and 100 nmol) caused moderately severe hind limb paralysis whereas DYN A-(1-8) did not cause any motor impairment up to the dose of 100 nmol. MR 1452, a relatively preferential antagonist of the kappa opioid receptor, prevented both the antinociceptive and motor effects of dynorphins. Intrathecal somatostatin (25 nmol) had a profile of activity superimposable on that of DYN A (1-32): long-lasting (up to 24 h) elevation of tail-flick latency with hind limb paralysis, and a shorter (4 h) elevation of the vocalization threshold. MR 1452 did not modify these effects. Intrathecal neurotensin (25 nmol) and s-CT (0.5 nmol) did not alter tail-flick latency or vocalization threshold. However, adopting the hot plate as the analgesimetric test, both peptides elevated the time of hind paw licking, taken as an index of nociception. No signs of motor dysfunction were observed at the doses employed. PMID- 2904672 TI - [Oncogenes: risk and prognostic factors in cancer of the breast]. PMID- 2904673 TI - [Hemodynamic correlates of selective beta 1 adrenergic receptor blockade by cordanum during hemiton monotherapy in children with primary arterial hypertension]. PMID- 2904674 TI - [Nephrotic syndrome after a medusa sting]. AB - A steroid-responsive nephrotic syndrome after medusa prick is not common. It occurred in a 15 year-old girl: this case allows to discuss the role of allergy in such a situation. PMID- 2904675 TI - Resistant duodenal ulcer: when, why and what to do? PMID- 2904676 TI - An inhibitor of the in vitro elongation reaction of simian virus 40 DNA replication is overcome by proliferating-cell nuclear antigen. AB - The replication of simian virus 40 (SV40) origin-containing DNA has been reconstituted by using SV40 large tumor (T) antigen and cellular proteins purified from HeLa cells. This replication reaction is unaffected by proliferating-cell nuclear antigen (PCNA). In contrast, PCNA has been reported to stimulate SV40 DNA synthesis carried out with crude fractions [Prelich, G., Kostura, M., Marshak, D. R., Mathews, M. B. & Stillman, B. (1987) Nature (London) 326, 471-475]. This difference is caused by the presence of a protein in crude fractions that inhibits the elongation of nascent DNA chains during replication. In the presence of PCNA, crude fractions containing this elongation inhibition factor can extend DNA chains. We describe the partial purification of this inhibitor and show that its addition limited SV40 DNA replication to the synthesis of short chains, an effect reversed by the addition of PCNA. However, the reversal of the inhibition by PCNA in the SV40 system required additional protein fractions distinct from PCNA and the enzymes constituting the purified system. These results suggest that the PCNA-mediated effect on SV40 DNA replication may be indirect. Such an interplay between negative and positive regulatory functions including PCNA may contribute to the control of DNA synthesis characteristic of the eukaryotic cell cycle. PMID- 2904677 TI - Purification and reconstitution of the proton-translocating ATPase of Golgi enriched membranes. AB - Kidney cortex microsomes enriched in Golgi markers and probably also containing endosomes were isolated by cell fractionation and found to contain a proton translocating ATPase that was inhibited by N-ethylmaleimide (NEM). This NEM sensitive ATPase was solubilized with n-octyl glucoside and purified using anion exchange sievorptive chromatography on sequential DEAE-Sephadex and QAE-Sephadex columns followed by a final hydroxyapatite HPLC column. The purified enzyme, with a specific activity of 4.4 mumol.mg-1.min-1 was completely inhibited by NEM. Addition of asolectin and removal of the detergent by dialysis resulted in reconstitution of NEM-sensitive electrogenic proton transport. This vacuolar ATPase is composed of five polypeptides with apparent molecular masses of 68, 58, 40, 37, and 16 kDa. PMID- 2904678 TI - Isolation and characterization of a Xenopus laevis C protein cDNA: structure and expression of a heterogeneous nuclear ribonucleoprotein core protein. AB - The C proteins are major components of heterogeneous nuclear ribonucleoprotein complexes in nuclei of vertebrate cells. To begin to describe their structure, expression, and function we isolated and determined the DNA sequence of Xenopus laevis C protein cDNA clones. The protein predicted from the DNA sequence has a molecular mass of 30,916 kDa and is very similar to its human counterpart. Although mammalian genomes contain many copies of C protein sequence, the Xenopus genome contains few copies. When C protein RNA was synthesized in vitro and microinjected into stage-VI Xenopus oocytes, newly synthesized C proteins were efficiently localized in the nucleus. In vitro rabbit reticulocyte lysate and in vivo Xenopus oocyte translation systems both produce from a single mRNA two discrete polypeptide species that accumulate in a ratio similar to that of mammalian C1 and C2 proteins in vivo. PMID- 2904679 TI - Nerve growth factor increases mRNA levels for the prion protein and the beta amyloid protein precursor in developing hamster brain. AB - Deposition of amyloid filaments serves as a pathologic hallmark for some neurodegenerative disorders. The prion protein (PrP) is found in amyloid of animals with scrapie and humans with Creutzfeldt-Jakob disease; the beta protein is present in amyloid deposits in Alzheimer disease and Down syndrome patients. These two proteins are derived from precursors that in the brain are expressed primarily in neurons and are membrane bound. We found that gene expression for PrP and the beta-protein precursor (beta-PP) is regulated in developing hamster brain. Specific brain regions showed distinct patterns of ontogenesis for PrP and beta-PP mRNAs. The increases in PrP and beta-PP mRNAs in developing basal forebrain coincided with an increase in choline acetyltransferase activity, raising the possibility that these markers might be coordinately controlled in cholinergic neurons and regulated by nerve growth factor (NGF). Injections of NGF into the brains of neonatal hamsters increased both PrP and beta-PP mRNA levels. Increased PrP and beta-PP mRNA levels induced by NGF were confined to regions that contain NGF-responsive cholinergic neurons and were accompanied by elevations in choline acetyltransferase. It remains to be established whether or not exogenous NGF acts to increase PrP and beta-PP gene expression selectively in forebrain cholinergic neurons in the developing hamster and endogenous NGF regulates expression of these genes. PMID- 2904680 TI - Two classes of N-methyl-D-aspartate recognition sites: differential distribution and differential regulation by glycine. AB - The N-methyl-D-aspartate (NMDA) receptor, a subtype of excitatory amino acid receptor, mediates synaptic responses in many regions of the central nervous system. This receptor plays a critical role in the mechanisms of both synaptic plasticity and excitotoxicity. Although these receptors were generally thought to be a single homogeneous receptor population, we report observations indicating that two anatomically distinct forms of the NMDA-receptor complex exist. (i) The distribution of NMDA receptors, as labeled by the NMDA agonist L-[3H]glutamate, differs from that obtained with the radiolabeled antagonist 3H-labeled 3-[(+/-)2 carboxypiperazine-4-yl]propyl-1-phosphonic acid [( 3H]CPP). Relative to L [3H]glutamate, [3H]CPP binding is low in the striatum and septum and high in the thalamus and inner cerebral cortex. (ii) NMDA antagonists are relatively more potent than agonists at displacing L-[3H]glutamate binding in the thalamus and cerebral cortex; agonists are relatively more potent in the striatum and cerebellum. (iii) Glycine, which potentiates NMDA-receptor responses to glutamate, causes a greater percentage increase in L-[3H]glutamate binding to NMDA receptors in the thalamus and cerebral cortex than in the striatum, septum, and cerebellum. Radiolabeled NMDA-antagonist binding, in contrast, is inhibited by glycine. Thus, as observed for gamma-aminobutyric acid type A receptors, NMDA receptors have an agonist-preferring binding-site population and an antagonist preferring binding site population. These may represent two distinct receptors and/or two interconverting forms. It could be of significant clinical importance if these two sites differ in their response to NMDA. PMID- 2904681 TI - Expression of neurotransmitter transport from rat brain mRNA in Xenopus laevis oocytes. AB - To permit a molecular characterization of neurotransmitter transporter proteins, we have studied uptake activities induced in Xenopus laevis oocytes after injection of adult rat forebrain, cerebellum, brainstem, and spinal cord poly(A)+ RNA. L-Glutamate uptake could be observed as early as 24 hr after injection, was linearly related to the quantity of mRNA injected, and could be induced after injection of as little as 1 ng of cerebellar mRNA. Transport of radiolabeled L glutamate, gamma-aminobutyric acid, glycine, dopamine, serotonin, and choline could be measured in single microinjected oocytes with a regional profile consistent with the anatomical distribution of particular neurotransmitter synthesizing soma. Forebrain L-glutamate and dopamine uptake, as well as cerebellar L-glutamate transport, were found to be Na+-dependent. Cerebellar mRNA induced L-glutamate transport was both time and temperature-dependent, was saturable by substrate, suggesting a single activity with an apparent transport Km of 14.2 microM and a Vmax of 15.2 pmol/hr per oocyte, and was sensitive to inhibitors of brain L-glutamate transport. Thus, the oocyte L-glutamate transport induced by injection of adult rat cerebellar mRNA appears essentially identical to the high-affinity, Na+-dependent L-glutamate uptake found in brain slices and nerve terminals. Experiments with size-fractionated cerebellar mRNA reveal single, comigrating peaks for cerebellar L-glutamate and gamma-aminobutyric acid transport, with peak activity obtained in fractions of approximately 2.7 kilobases, suggesting the presence of single or similarly sized mRNAs encoding each of these activities. PMID- 2904682 TI - Hypoglycaemic agents which do not release insulin. PMID- 2904683 TI - Immunology of infection with the human immunodeficiency virus. PMID- 2904684 TI - [Hypersensitivity reaction to sulfasalazine with a clinical picture similar to mononucleosis]. PMID- 2904685 TI - Early clinical experience in reversing benzodiazepine sedation with flumazenil after short procedures. AB - Flumazenil (Flu) (Ro 15-1788, Anexate) is a newly synthetized specific benzodiazepine (BZD) antagonist which was recently introduced for clinical study. The drug was intravenously injected, in titrated doses, to patients undergoing diagnostic or therapeutic procedures in order to reverse the sedative effects of BZDs. A total of 63 patients undergoing hand surgery under i.v. regional block, lower abdominal surgery under epidural anesthesia, cardiac catheterization, intracardiac catheter ablation, cardioversion, gastroscopy and bronchoscopy were studied. Flu in a dose ranging from 0.1 to 0.42 mg effectively reversed BZD induced sedation in all patients 1-2 min following i.v. injection. Patients were fully awake and oriented yet calm and in good mood. Flu was well tolerated even in the high risk cardiac patients, with no significant changes in vital signs nor any sign of local irritation at the site of Flu injection. No significant resedation was observed. Thus Flu was very useful in reversing BZD-induced sedation or unconsciousness in a variety of clinical situations. PMID- 2904686 TI - The use of flumazenil in the treatment of 34 intoxicated patients. AB - The efficacy and safety of the newly available benzodiazepine (BDZ) antagonist flumazenil (Ro 15-1788, Anexate) was prospectively evaluated in the treatment of 34 intoxicated patients. Twenty-three patients had attempted suicide with various drugs, and 11 suffered iatrogenic BDZ overdose. Following 0.2 mg i.v. flumazenil (Flu) injection, 22 patients intoxicated mainly with BDZ (11 iatrogenic and 11 intentional) regained full consciousness within two minutes, enabling even extubation of two. Eight patients required repeated boluses or continuous infusion of Flu to maintain alertness. Five patients with mixed drug intoxication awakened only briefly and relapsed into unconsciousness. In spite of Flu doses of up to 20 mg, no effect on consciousness was observed in 7 patients, intoxicated mainly with non-BDZ drugs. No significant side effects were noted attributable to Flu which has proved to be a safe and effective drug. It may be employed to achieve complete reversal of pure BDZ overdose, or for 'unmasking' the relative action of BDZ in mixed drug overdose. The danger of complications from drug overdose may thus be lessened, obviating the need for invasive interventions such as mechanical ventilation and invasive hemodynamic monitoring, at the same time decreasing risk and expense. PMID- 2904687 TI - Clinical experiences with Ro 15-1788 (anexate) in benzodiazepine and mixed-drug overdoses. AB - Benzodiazepine overdose is the most common of admission to the Toxicological Unit of the University of Florence. The aim of this study has been to evaluate the efficiency of Ro 15-1788 in benzodiazepine and mixed drug overdoses. The administration of Ro 15-1788 was followed by a quick reversal of central nervous system depression and was more effective in benzodiazepine overdoses than in mixed drug overdoses. The dose was titrated individually and the range 2-10 mg was effective according to the conditions of the patient. In some cases, the comatose state relapsed; further administration of Ro 15-1788 again promptly reversed the condition. On awakening, two patients displayed anxiety and restlessness. PMID- 2904688 TI - Controlled sedation in ventilated intensive care patients. PMID- 2904689 TI - The use of anexate (Ro 15-1788) in acute self-poisoning with benzodiazepines alone or combined with other drugs--preliminary results. PMID- 2904690 TI - Drug treatment of mild hypertension to reduce the risk of CHD: is it worth-while? AB - Although hypertension is regarded as a causal factor for coronary heart disease (CHD) a reduction in the risk of CHD as a result of lowering blood pressure in mild hypertension could not be demonstrated. This conclusion is based on an overview analysis of all published randomized trials in mild hypertension, including more than 25,000 subjects contributing over 125,000 person years of observation. There is evidence that treatment reduces the risk of CHD in moderate to severe hypertension. In addition the pooling of four clinical trials with treated control groups indicates a reduction in the risk of CHD of borderline significance with beta-blockers or aggressive treatment when compared with standard treatment (mostly diuretics). The failure of drug treatment to reduce the risk of CHD in mild hypertension is consistent with the results from epidemiological studies because of derangement of the lipid profile induced by diuretics and beta-blockers. PMID- 2904691 TI - [Predictive signs of development of AIDS after the analysis of a cohort of seropositive individuals followed for two years]. PMID- 2904692 TI - [Techniques of DNA polymorphisms revealed by probes for the Y chromosome applied to questions of father-son line in analyses of paternity]. AB - The Y specific probe (two 49f and 49a sub-clones) is a polymorphic one for the A (5 alleles), C (2 alleles), D (3 alleles), F (2 alleles) and I (2 alleles). We show that the corresponding allelic combinations, or haplotypes, are transmitted father-to-son in eleven random chosen families. Utilisation of these polymorphisms in other eleven father-son paternitity cases, studied for a panel of erythrocytic and seric markers, shows a good correlation between the two approaches, most of the paternies excluded by the Y probes being also excluded with other allotypic markers. Utilisation of this sort of polymorphism does not necessitate the knowledge of maternal genotype in families studied. PMID- 2904693 TI - Event-related brain potentials: a window on information processing in schizophrenia. AB - The application of the P300 component of the event-related brain potential to the study of attentional impairment in schizophrenia is discussed, and two recent studies are described. In one, the relative effects on P300 of stimulus modality and probability were evaluated. The data showed that the P300 is smaller in schizophrenic patients relative to normal controls for low-probability auditory stimuli. Next is described a preliminary report that evaluated whether this P300 reduction reflects a core deficit (trait marker) or clinical symptomatology (state marker). To pursue this question, a group of schizophrenic patients was studied on and off neuroleptic medication. The data showed that improvement in clinical state was highly correlated with increased visual P300 but was uncorrelated with auditory P300. These findings suggest that P300 elicited in the visual modality has the characteristics of a state marker of schizophrenia. In contrast, auditory P300 remains a candidate for a vulnerability trait marker of schizophrenia. The core deficit in schizophrenia thus appears to involve the auditory information-processing system, whereas fluctuations in clinical state may be reflected in the visual processing system. PMID- 2904694 TI - Perspectives on a time-dependent model of neuroleptic action. AB - The best support for the hypothesized involvement of central nervous system dopamine systems in the pathophysiology of schizophrenia is the association between the affinity of neuroleptic drugs for the D2 dopamine receptor and their potency as antipsychotics. Discrepancy between the time course of receptor binding and the development of antipsychotic effects, however, limits this model. Preclinical studies have now shown that activation of presynaptic nigrostriatal and mesolimbic dopamine neurons by acute neuroleptic administration is reversed during chronic administration. Clinically, neuroleptic-induced time-dependent reductions in plasma levels of the dopamine metabolite, homovanillic acid (HVA), have been linked to the antipsychotic response in schizophrenic patients. These data support the notion that slowly developing alterations in presynaptic dopamine activity play a role in the mechanism of action of neuroleptic drugs. Differences between plasma and cerebrospinal fluid (CSF) HVA responses to neuroleptic treatment, although not fully explained, may be related to prominent contributions of mesocortical metabolism to CSF levels of HVA. A time-dependent dopaminergic model of neuroleptic action with implications for the pharmacotherapy of schizophrenia is presented. PMID- 2904695 TI - The therapeutic latency of neuroleptic drugs and nonspecific postjunctional supersensitivity. AB - It is suggested that the antidopaminergic effects of neuroleptics are not directly responsible for the antipsychotic effect but, rather, that the antipsychotic effect is related to secondary changes in the efficacy of transmission at corticostriatal excitatory synapses. Arguments are presented in support of the following: (1) acute dopaminergic antagonism produces a relatively nonspecific sedation or deactivation, but most of the amelioration of psychosis develops slowly; (2) the development of dopaminergic supersensitivity is responsible for tolerance to the sedative effects of neuroleptics; and (3) excitatory synapses of the corticostriatal pathway, mediated by glutamic acid, are located on the same dendritic spines as the striatal dopaminergic synapses. Concomitant with the development of dopaminergic supersensitivity, these glutamate synapses become subsensitive. The glutamatergic subsensitivity is a result of the nonspecific nature of postsynaptic denervation supersensitivity. It is suggested that subsensitivity of striatal glutamate-mediated synapses is directly responsible for the antipsychotic effect of neuroleptic drugs. In support of this hypothesis, chronic neuroleptic administration was found to decrease the behavioral responsivity of mice to the glutamate agonist, quisqualic acid, and to the the antagonist, glutamic acid diethyl ester. PMID- 2904696 TI - Vitamin E in the treatment of tardive dyskinesia: the possible involvement of free radical mechanisms. AB - One of the major problems associated with long-term neuroleptic treatment is persistent tardive dyskinesia (TD), for which there is no satisfactory treatment. We have recently proposed that some cases of TD are associated with neuronal dysfunction resulting from excess free radical production occurring during catecholamine metabolism. We therefore decided to assess the efficacy of a powerful free radical scavenging agent, alpha-tocopherol (vitamin E), on the clinical signs of TD. We treated 15 patients with persistent TD with alpha tocopherol and matched placebo in a randomized crossover design. Patients demonstrated a significant overall reduction in scores on the Abnormal Involuntary Movements Scale (AIMS) after treatment with alpha-tocopherol, but not after placebo. The mean reduction in the AIMS score with alpha-tocopherol was 43 percent, with seven patients showing a greater than 50 percent reduction in their dyskinesia. There was also a trend for a decrease in scores on the Brief Psychiatric Rating Scale, but no change was observed in scores on the Simpson Angus Scale for Extrapyramidal Side Effects. Our findings are consistent with the possibility that alpha-tocopherol is beneficial in the treatment of some patients with TD, but further research is necessary to establish the efficacy of this agent. PMID- 2904697 TI - Mitochondrial DNA polymorphism in Chinese. AB - Human mitochondrial DNA (mtDNA) restriction endonuclease fragment patterns were analyzed using placenta DNA isolated from 273 individuals representing four different nationalities, the Han, the Uygur, the Kazakh and the Hui populations. Thirty-eight fragment patterns (morphs) were observed with the enzyme ApaI, BamHI, EcoRI, HindIII, HinfI, HhaI, HapII, KpnI, Mbol, PstI, PvuII, SacI, ScaL and XhoI. Fourteen new morphs, including some only existing in individual racial and national populations were observed, which indicates that there is a significant difference in the distribution of mtDNA morphs among various national and racial populations. By comparison with the mtDNA sequences in primate species, some mtDNA ancestral morphs were found to be retained in Oriental population today. This result provided indirect evidence that Asia may be one of the human original sources. Genetic distances among four national populations computed and employed in construction of an average linkage tree suggested that the Uygur and the Kazakh populations combined to form a branch at first, then the Han and the Hui came together to form another one, and at last, these two branches converged into a stem. Again, it was found that the internal variation within the Uygur and the Kazakh populations was greater than that within the Han and the Hui populations. These results showed a relationship among the four different national populations in China based on the molecular level. PMID- 2904698 TI - Living with clathrin: its role in intracellular membrane traffic. AB - Clathrin polymerization at the cytoplasmic side of the plasma membrane forms coated pits and vesicles that mediate uptake of cell surface receptors. Clathrin coated vesicles have also been implicated in protein export but definition of their precise role has been controversial. Recent advances in characterization of the clathrin subunits and additional coated vesicle components have identified molecular interactions involved in clathrin polymerization and coated vesicle formation, and have provided new approaches to investigating its function. These studies suggest that clathrin's role, in both inward and outward membrane traffic, is to facilitate receptor transport by a concentration and sorting process that initiates targeting to specific intracellular compartments. PMID- 2904699 TI - Metabolic correction of defects in the lipid anchoring of Thy-1 in lymphoma mutants. AB - Many plasma membrane proteins, including Thy-1, are anchored by a carboxyl terminal glycophospholipid. This unit is absent from the Thy-1 of several lymphoma mutants that synthesize the Thy-1 polypeptide but fail to express it at the cell surface. Recessive mutants of complementation groups A to C, E, and F contain Thy-1 mRNA of normal size, which suggests that their Thy-1 polypeptide is normal. To identify possible metabolic lesions, each mutant was grown with various supplements. The class F and B mutants exhibited a reversible induction of surface lipid anchored Thy-1 when grown with the aminoglycoside G418. Other aminoglycosides, sugars, and ethanolamine were inactive. These unexpected observations are discussed in the context of lipid anchor biosynthesis. PMID- 2904700 TI - More dimensions for glutamate toxicity. PMID- 2904701 TI - Contributions of quisqualate and NMDA receptors to the induction and expression of LTP. AB - The contributions of two subclasses of excitatory amino acid transmitter receptors to the induction and expression of long-term potentiation (LTP) were analyzed in hippocampal slices. The quisqualate/kainate receptor antagonist DNQX (6,7-dinitro-quinoxaline-2,3-dione) blocked 85% of the evoked field potential, leaving a small response that was sensitive to D-AP5 (D-2-amino-5 phosphonopentanoate), an N-methyl-D-aspartate (NMDA) receptor blocker. This residual D-AP5-sensitive response was of comparable size in control and previously potentiated inputs. High-frequency stimulation in the presence of DNQX did not result in the development of robust LTP. Washout of the drug, however, revealed the potentiation effect. Thus NMDA-mediated responses can induce, but are not greatly affected by, LTP; non-NMDA receptors, conversely, mediate responses that are not needed to elicit LTP but that are required for its expression. PMID- 2904702 TI - Repair of the secretion defect in the Z form of alpha 1-antitrypsin by addition of a second mutation. AB - Homozygous inheritance of the Z-type mutant form of the alpha 1-antitrypsin (alpha 1AT) gene results in the most common form of alpha 1AT deficiency, a human hereditary disease associated with a high risk for the development of emphysema and an increased incidence of neonatal hepatitis. The alpha 1AT-synthesizing cells of individuals with the Z gene have normal alpha 1AT messenger RNA levels, but alpha 1AT secretion is markedly reduced secondary to accumulation of newly synthesized alpha 1AT in the rough endoplasmic reticulum. Crystallographic analysis of alpha 1AT predicts that in normal alpha 1AT, a negatively charged Glu342 is adjacent to positively charged Lys290. Thus the Glu342----Lys342 Z mutation caused the loss of a normal salt bridge, resulting in the intracellular aggregation of the Z molecule. The prediction was made that a second mutation in the alpha 1AT genet that changed the positively charged Lys290 to a negatively charged Glu290 would correct the secretion defect. When the second mutation was added to the Z-type complementary DNA, the resulting gene directed the synthesis and secretion of amounts of alpha 1AT similar to that directed by the normal alpha 1AT complementary DNA in an in vitro eukaryotic expression system. This suggests the possibility that a human hereditary disease can be corrected by inserting an additional mutation in the same gene. PMID- 2904703 TI - Engraftment of immune-deficient mice with human hematopoietic stem cells. AB - A system in which immune-deficient mice are repopulated with cells from the human myeloid lineage, and that provides an in vivo stem cell assay for human hematopoietic cells is described. Generation of the chimeric human/immune deficient (HID) mice was dependent on the use of immune-deficient bg/nu/xid mice. Infusion of these mice with human bone marrow gave rise to increases in human macrophage progenitors during more than 5 weeks of in vivo growth, indicating the seeding, proliferation, and differentiation of human stem cells. The human identity of the progenitors was confirmed by sequence analysis and their dependence on human growth factors. The creation of HID mice lays the foundation for establishing animal models for a wide variety of human hemopathies, from leukemia to infectious disease. PMID- 2904704 TI - [Kidney involvement in the severe form of hemorrhagic fever with renal syndrome]. PMID- 2904705 TI - [Dopamine receptor stimulants in the treatment of alcoholism]. PMID- 2904706 TI - Direct comparison of the effects of nitroprusside, SIN 1, and various nitrates on platelet aggregation and soluble guanylate cyclase activity. AB - We have directly compared the effects of the nitrates isosorbide-5-mononitrate, nitroglycerin and isosorbide dinitrate and of the nitric oxide-containing sodium nitroprusside and 3-morpholino-sydnonimine (SIN 1) as well as of the bioinactive precursor of SIN 1, molsidomine, on platelet activating factor-induced platelet aggregation and activation of soluble guanylate cyclase. The effects of these agents on the aggregation and on soluble guanylate cyclase activity of human platelets were closely correlated. Whereas nitroprusside and SIN 1 were very potent inhibitors of aggregation and activators of soluble guanylate cyclase in micromolar concentrations, the other drugs were effective only at millimolar concentrations. Preincubation of platelets with cysteine did not or only slightly increase the ability of isosorbide-5'-mononitrate and isosorbide dinitrate to inhibit aggregation, but a clear increase was observed after preincubation with nitroglycerin. These data support the concept that cyclic GMP is the mediator of nitric oxide-induced inhibition of platelet aggregation and indicate that nitrates cannot directly inhibit aggregation or be converted to nitric oxide containing agents by a specific mechanism in platelets. The data also suggest that SIN 1 and nitroprusside, but not or only to a certain degree the nitrates, can be considered as exogenous endothelium-derived relaxing factors. PMID- 2904708 TI - [Health. A challenge to physicians?]. PMID- 2904707 TI - Effects of taxol and colchicine on platelet membrane properties. AB - The effects of the assembly-disassembly of microtubule on the membrane lipid fluidity, the fragmental motion of sulfhydryl groups of membrane proteins, and the functions of shape change and hypotonic shock response (shrinkage ratio) in human platelets were studied. We have employed electron spin resonance (ESR) utilizing spin labels for bilayer lipids or membrane proteins and microtubule reactive reagents to change microtubule assembly. Both, taxol, a microtubule stabilizing agent, and colchicine, a microtubule disrupting agent, did not affect the platelet membrane lipid fluidity detected by 5- or 16-doxylstearate. On the other hand, the mobility of sulfhydryl groups detected by 4-maleimide-tempo increased by taxol treatment and decreased by colchicine. Moreover, the temperature sensitivity of platelets below 20 degrees C decreased by taxol treatment, but unchanged by colchicine treatment. This behavior was similar to the shape change ability or the shrinkage ratio of platelets pre-treated with taxol, in which microtubule disassembly was inhibited due to taxol binding to microtubule. Therefore, it is confirmed that the assembly-disassembly state of microtubule which may control the ability of platelets to change shape, influences the mobility of sulfhydryl groups in platelet membrane proteins and its temperature sensitivity. PMID- 2904709 TI - [Drug therapy of paranoid conditions]. PMID- 2904710 TI - [Symptoms in a normal population]. PMID- 2904711 TI - Examination of the interaction of decis and dithane in rats. AB - Acute (LD50) and short-term (14 days) toxicological examinations were performed in animal experiments on the interaction of a synthetic pyrethroid Decis 2,5 EC (25 g deltamethrin/l) and of ethylene-bisdithiocarbamate/Dithane M-45 (80% mancozeb), using a 1:5 deltamethrin/mancozeb mixture. LD50 value of the mixture was similar to that of the more toxic Decis. In the short-term examination, some pathologically high AST and ALT values were observed in the treated groups and the deltamethrin content of fatty tissue samples increased parallel with the increase of Decis consumption. The chymotrypsin and lipase activities in the small intestinal mucosa and gamma-GT and LAP activities in the content of the bowels were reduced in several treated groups. The administration of Dithane in a dose in accordance with 20% of the LD50 value (3125 mg/kg b.m.) proved to be more toxic than expected and caused the death of the animals. PMID- 2904712 TI - Palytoxin induces a relatively non-selective cation permeability in frog sciatic nerve which can be inhibited by cardiac glycosides. AB - The effect of palytoxin (PTX) on compound resting potential and compound action potential of frog sciatic nerve was studied using the sucrose-gap technique. PTX irreversibly depolarized the compound resting potential and reduced the amplitude of the compound action potential. PTX evoked a marked depolarization when extracellular Na+ was replaced by Li+, Cs+ and the organic cations methylammonium, hydroxylammonium, and methylhydroxylammonium but not by tetramethylammonium, tetraethylammonium, choline or the divalent cations, Ca2+ and Ba2+. The maintained depolarization was not sensitive to inhibition by saxitoxin (300 nM) or procaine (10 mM). The depolarization was inhibited by ouabain or cymarin but not by the aglycon, strophanthidin. However, strophanthidin did antagonize the inhibitory action of cymarin which suggests that PTX and cardiac glycosides do not share an identical binding site but there may be some overlap. We conclude that in frog sciatic nerve, PTX interacts with the (Na+-K+) pump to induce the opening or formation of a relatively non selective cation pore within or near the pump protein. PMID- 2904713 TI - Analytical problems encountered during high-performance liquid chromatographic separation and coulometric detection of bopindolol metabolites in human plasma. AB - Good clinical control of hypertension is achieved with low doses of the potent beta-blocker bopindolol. Pharmacokinetic evaluations therefore require an analytical technique of high sensitivity. Analysis of plasma by high-performance liquid chromatography (HPLC) using electrochemical detection provides this sensitivity. This article describes the development of an analytical procedure and presents a reversed-phase HPLC method with coulometric detection suitable for plasma analyses during pharmacokinetic investigations of bopindolol therapy. PMID- 2904714 TI - Abrogation or exacerbation of graft-versus-host disease by transfusing hematopoietic stem cell donors with recipient-specific blood. PMID- 2904715 TI - [An open debate with people about AIDS]. PMID- 2904716 TI - Klinefelter's syndrome with hypospadias and bilateral cryptorchidism. AB - A 3-year-old boy was found to have abnormality of the external genitalia at birth. Physical examination revealed hypospadias penis and bilateral cryptorchidism. Chromosomal analysis of peripheral blood showed the karyotype of 47,XXY, and the diagnosis of Klinefelter's syndrome associated with hypospadias and cryptorchidism was made. Klinefelter's syndrome is rare in infancy. PMID- 2904717 TI - [HIV-1 infection: pathogenesis of immune suppression]. AB - Although, in the course of HIV-1-infection, the functional capacities of virtually all immune cells are greatly impaired, only CD4+ cells (antigen presenting cells, helper T cells) are directly infected by the virus. CD4+ T cells are involved, to a greater or lesser degree, in the induction of virtually all immunologic phenomena, either directly or indirectly. Thus, it is clear that the HIV-1-induced depletion and functional impairment of this critical T cell subset will result in a dysfunction/deficiency of the entire immune system and, finally, in the development of opportunistic infections and neoplasms. PMID- 2904718 TI - [The significance of inflammatory vascular diseases]. AB - Out of the from angiological points of view most important inflammatory vascular diseases (obliterating endangiitis, giant cell arteriitis, Takayasu's disease) epidemiological data are compiled. Remarkable is the increasing part of female patients in endangiitis. Furthermore it is referred to the particular functional situation in these vascular diseases, which results from the localisation of a peripheral occlusion, insufficient formation of collaterals or disturbed rheology. PMID- 2904719 TI - [Clinical aspects and functional diagnostic findings of Takayasu disease]. AB - Aetiopathogenesis, clinical picture, laboratorical and functional diagnostic methods of ten patients suffering from Takayasu's arteritis out of 1164 patients suspicious of cerebrovascular insufficiency are described. The combined use of Dopplersonography, ophthalmodynamometry and ophthalmodynamography permit in all cases the assessment of vascular pathology in supraaortic arteries. The specific diagnosis was made in connection which clinical, anamnestical and paraclinical findings. There are some characteristic functional diagnostic results in Takayasu's arteritis. The noninvasive diagnostic methods are useful tools to estimate the progredience of this disease in his chronical course. PMID- 2904720 TI - Nutrient transport in Candida albicans, a pathogenic yeast. PMID- 2904721 TI - Factors affecting the outcome of orchiopexy for undescended testis. AB - Orchiopexy was performed on 135 testes in 121 patients aged up to 15 (median 6) years who had no previous inguinal surgery or hormonal treatment. Hypoplasia at the time of orchiopexy (34/135) was significantly less common when the testis was in or peripheral to the superficial inguinal ring than when it was intracanalicular. The position did not influence the outcome of surgery or the risk of postoperative hypoplasia (9 cases). At follow-up 87% of the testes were in the scrotum. Reoperation was required for four of nine which were anchored to the femoral skin or with suture through testis and scrotal wall. Tension on the spermatic cord significantly increased the failure risk. Simultaneous herniotomy was associated with 15%, and dissection only (including excision of the vaginal process remnant) with 6% orchiopexy failure. Retroperitoneal dissection to avoid tension on the cord significantly reduced the failure rate without increasing the risk of postoperative hypoplasia. Orchiopexy performed with optimal technique by experienced surgeons is a safe and effective alternative to hormonal treatment. PMID- 2904722 TI - Further evidence that brain histamine H2 receptors are stimulatory in the control of prolactin in the rat. AB - The effects of administration into the brain ventricle of H2 receptor agonists (4 methylhistamine, 0.8 mumol/rat; dimaprit, 0.4-0.8 mumol/rat), H2 antagonists (cimetidine, 0.8 mumol/rat; ranitidine, 0.4-0.8 mumol/rat; famotidine, 0.03 mumol/rat) and of the dimaprit chemical analogue SK&F 91487 (0.4 mumol/rat) on unstimulated and histamine-stimulated prolactin secretion in normal male rats were studied. The H2 agonist 4-methylhistamine caused a significant increase in unstimulated blood PRL, whereas dimaprit, SK&F 91487, and the H2 antagonists tested did not change PRL levels. 4-Methylhistamine significantly enhanced the stimulatory effects of histamine on prolactin, whereas all the H2 antagonists inhibited histamine-induced prolactin release. The inhibition of histamine induced prolactin secretion by the H2 agonist dimaprit is nonspecific, since its chemical analogue SK&F 91487, which has no H2 agonist activity, also inhibits it. These results indicate that stimulation of the H2 receptors in the central nervous system is facilitatory for PRL secretion, suggesting that the activation of H2 receptors may contribute to the PRL-releasing effects of histamine. PMID- 2904723 TI - Impaired ability of T4+ lymphocytes in the active stage of congenital hypoplastic anemia to promote in vitro growth of blood erythroid burst-forming units (BFU-E). PMID- 2904724 TI - Expression of Thy-1 antigen on hematopoietic progenitors during murine development. PMID- 2904725 TI - Alternating hyper- and hypothyroidism with thyroid-stimulating and TSH-binding inhibition immunoglobulins. PMID- 2904726 TI - Age-dependent variation in the sensitivity of rat brain glutamine synthetase to L methionine-DL-sulfoximine. AB - Effects of a subacute dose (150 mg/kg body wt) of methionine sulfoximine was studied on the behavioural changes and glutamine synthetase activity in cerebral cortex, cerebellum and brain stem of rats of four different age groups. Animals of 10 days and 90 days age groups were less vulnerable to the toxic effects of methionine sulfoximine. Rats of 180 days age exhibited various behavioural changes upon the administration of methionine sulfoximine and entered into convulsions at the end of 17 hr. In rats of 360 days age group these changes appeared quite early and the animals convulsed at the end of 13 hr. Animals of these two age groups failed to recover from toxic effects of methionine sulfoximine. Methionine sulfoximine inhibited glutamine synthetase activity in the brains of rats of all age groups. Maximum inhibition of activity was noticed at the end of 12 hr in 10-day-old rats while in the animals of other age groups it was seen at the end of 3 hr. In animals of all age groups the enzyme activity was inhibited by 60-70% except in 360-day-old rats where the inhibition was 95%. Behavioural changes and inhibition of glutamine synthetase were out of phase with each other. It is suggested that the toxicity of methionine sulfoximine may not be due to its effect on glutamine synthetase alone. Further, these results also suggest that the toxic effects of methionine sulfoximine vary with the age of the animal. PMID- 2904727 TI - Studies on glutamine and asparagine synthetases from mixed rumen bacterial flora of buffaloes and cattle. PMID- 2904728 TI - Cardiovascular and pulmonary effects of a new sedative/analgesic (medetomidine) as a preanaesthetic drug in the dog. PMID- 2904729 TI - The DC-recorded dog electroretinogram in ketamine-medetomidine anaesthesia. PMID- 2904730 TI - Genetic relatedness of the Kemerovo serogroup viruses: I. RNA-RNA blot hybridization and gene reassortment in vitro of the Kemerovo serocomplex. AB - The dsRNA profiles of the Czechoslovakian and Siberian serotypes of the Kemerovo serocomplex viruses examined were similar in agarose, while their dsRNA profiles were distinct in polyacrylamide gel. Blot hybridization studies of the Kemerovo serocomplex viruses demonstrated that the genes were highly conserved among the members within each type, but not between types. Gene reassortment in vitro was demonstrated among selected pairs of the Kemerovo serocomplex viruses by intra- and inter-typic crosses. The majority of the reassortant progeny from inter-typic crosses were single gene replacements, whereas the majority of the reassortant progeny from intra-typic crosses were multiple gene replacements suggesting that certain gene combinations were restrictive under conditions of the experiment. PMID- 2904731 TI - Herpes simplex virus type 1 (HSV-1) HSZP interferes also heat inactivated with early shutoff of host protein synthesis induced by HSV-1 KOS. AB - The ability of two strains of herpes simplex virus type 1 (HSZP and KOS) to shut off the host protein synthesis in the presence of Actinomycin D was investigated. The HSZP strain proved to be defective with respect to the so-called early shutoff function. In superinfection experiments, the HSZP was effective at interfering with the early shutoff function of the KOS strain provided that the HSZP infection preceded KOS superinfection. Heat inactivation of the HSZP did not lead to the loss of its interfering ability. Evidence was given that this interference was neither due to the hindrance of the KOS by HSZP at adsorption nor due its exclusion during penetration. PMID- 2904732 TI - Inhibitory effect of sulphur-containing purine nucleoside analogues on replication of RNA viruses: selective antiviral activity against influenza viruses. AB - Four sulphur-containing purine nucleoside analogues: 6MP, 6-thioinosine, 6 methylthioinosine and 6-ethylthioinosine, were examined for antiviral activity against some RNA viruses. All compounds extensively inhibited the replication of influenza viruses but had no inhibitory effect on other RNA viruses: Sendai, RS, vesicular stomatitis and western equine encephalitis viruses. PMID- 2904733 TI - Characterization of monoclonal antibodies to adenovirus type 35 hexon. AB - Twenty three monoclonal antibody-rich ascitic fluids (MIAFs) to human adenovirus (AV) type 35 hexon were studied by indirect ELISA using various tracer systems, passive haemagglutination (HA) as well as gel diffusion techniques. Eleven different human heterologous hexon types in addition to the homologous one, and two animal adenovirus (AV) hexons were used to determine the reactivity patterns (RPs) of the monoclonal antibodies (MoAbs). Based on the cross-reactivity with the different hexon types, the MoAbs exhibited genus, subgenus and type specificities; furthermore, a variety of intersubgenus and intertype specificities could be found. Fifteen of the MoAbs reacted in ELISA, but not in passive HA, suggesting that certain epitopes on the hexons bound to red blood cells were not available for the MoAbs in question. Four MoAbs were able to form a precipitin line with the hexon antigen in gel diffusion. Two of the four (MoAbs 35H10 and 35H51) formed with the homologous AV35 hexon a single confluent precipitin line only. In spite of the origin of these MoAbs from different hybrid cells (clones) their specificity was probably identical when recognizing the type specific epitope of the AV35 hexon. The other two MoAbs (35H15 and 35H26) with a broad RPs were able to precipitate not only the homologous but also different heterologous hexon types. PMID- 2904734 TI - Interaction between anti-influenza viral polymerase antibodies and RNP particles using the in vitro transcription process and an immunogold labelling technique. AB - Immunogold labelling and in vitro transcription of influenza virus vRNA have been used to analyse the interaction of anti-influenza polymerase antibodies with influenza-ribonucleoprotein (RNP) complexes. The polymerase proteins (P proteins) were localized exclusively at one end of the RNP segments. In the course of transcription the amount of P protein decreased significantly. The in vitro transcriptase activity y of influenza A virus RNP complexes in the presence of anti-polymerase antibodies to the strain A/PR/8/34 was inhibited by 60%. In contrast, RNP transcriptase activity of influenza B virus was not inhibited by these antibodies. PMID- 2904735 TI - Antigenic properties of vaccinia virus and of the virus recombinant strains expressing heterologous genes. AB - Immunologic properties of vaccinia virus (VV), strain LIPV, and VV recombinant strains containing the gene of hepatitis B virus surface antigen and the TK gene of herpes simplex virus (HSV) have been studied. Production of antibodies against the majority of VV structural proteins, including nucleocapsid internal proteins was demonstrated in rabbits. Insertion of heterologous genes into the VV genome was without effect on the spectrum of antibodies produced against VV virion proteins. The data obtained in volunteers indicate that not only virus neutralizing antibodies but also antibodies against most VV structural proteins are preserved in humans over many years. Reimmunization of volunteers with VV recombinant stimulates synthesis of antibodies against virion proteins whereas the spectrum of antibodies remains unchanged. Humans and rabbits did not differ in the spectrum of antibodies to VV virion proteins. PMID- 2904736 TI - Effects of cis-dichloro-diammine-platinum (II) (cis-DDP) on Epstein-Barr virus induction and cell differentiation. AB - Morphological changes were induced by cis-dichlorodiammine platinum (II) (cis DDP) in two Epstein-Barr virus (EBV) transformed cell lines: the productive P3HR 1 and the nonproductive Raji cell line. In P3HR-1 cells cis-DDP induced synthesis of viral antigens, viral particles and morphological changes characteristic for virus replication. In Raji cells, the virus replicative cycle was not induced and virus-specific morphological changes were limited to the sporadic appereance of some very early alterations in cell morphology. However, in Raji cells, but not in P3HR-1 cells, up to 20 per cent of the cell population exhibited differentiation-related changes towards plasma cell morphology. The most advances stage of cell differentiation detected was classified as plasmablast. Cis-DDP also induced some changes associated with the cytostatic effect of the drug. In the treated cell population cytokinesis was inhibited and frequently multinuclear cells appeared; moreover, extensive degenerative changes were observed. PMID- 2904737 TI - Accumulation dynamics of the agent of amyotrophic leukospongiosis and the development of degenerative changes in the central nervous system of guinea pigs. AB - After retrobulbar inoculation into guinea pigs, the agent of amyotrophic leukospongiosis was detected in the central nervous system (CNS) as early as 7 days post-infection (p.i.), whereas specific morphological changes appeared since days 14 to 21 p.i. Virological and morphological findings suggested that motoneurons of the spinal cord were first damaged in the course of the pathologic process which then proceeded upwards. PMID- 2904738 TI - Attempts at the detection of antibodies to Newcastle disease virus by haemofusion inhibition test. AB - Two modifications of a haemofusion-inhibition test (HFI-1 and HFI-2) were applied for the titration of antibodies to Newcastle disease virus (NDV) in chicken sera. Statistical analysis revealed a positive correlation of the HFI-1 antibody titres with those measured by the standard haemagglutination-inhibition (HI), virus neutralization (VN) and haemolysis-inhibition (HLI) tests. The same appeared true when the HFI-2 antibody titres were compared with the HI, VN, and HLI tests. Except for the several sera collected from birds immunized with formalin inactivated vaccine, the HFI-2 antibody titres of individual serum samples were usually lower than those determined by HFI-1. The interpretation of these differences as well as some advantages and disadvantages of the proposed test are discussed. PMID- 2904739 TI - Use of enzyme-linked immunosorbent assay for the determination of serological relationship between two comoviruses. AB - ELISA was used to determine the degree of serological relationship between red clover mottle (RCMV) and broad bean stain (BBSV) viruses and the optimal conditions for the differentiation of the two viruses by ELISA were established. The titres of homologous and heterologous antibodies determined by ELISA were 100 to 200-fold higher as compared with the ring precipitin test. Antigen concentrations of 0.15 and 0.075 ng/ml, respectively, could be detected. The reactions in ELISA depended on the concentration of antigen, of IgG used for coating and of conjugated IgG. In anti-RCMV IgG, the ratio of group-specific to species-specific antibody as determined by ELISA was from 1:1 to 1:2, while in anti-BBSV IgG this ratio was from 1:4--1:8. The differences between homologous and heterologous reactions in ELISA suggested a similar ratio of antigenic determinants in the two viruses. PMID- 2904740 TI - Herpes simplex virus DNA in the brain of psychotic patients. AB - Herpes simplex virus (HSV) DNA was found by spot blot hybridization in the right nc. amygdalae of 3 out 10 patients who underwent curative stereotactic surgery for severe mental retardation with aggressive behavior and/or paranoic schizophrenia. Of these, 6 were also tested for the presence of CMV DNA sequences with negative results. Biopsy specimens from nc. amygdalae of another 7 psychotic patients were cultured in vitro but no virus was isolated. PMID- 2904741 TI - Kinetics of phospholipid extraction from Coxiella burnetii. AB - Kinetics of phospholipid extraction from purified suspensions of Coxiella burnetii in phase I by various chloroform--methanol mixtures at various temperatures were evaluated based on the amount of phosphorus extracted. Extraction by a boiling (53 degrees C) 2:1 chloroform:methanol mixture proved to be the most efficient. PMID- 2904742 TI - Participation of reticuloendothelial system in the pathogenesis of experimental amyotrophic leukospongiosis. AB - Spleen and peripheral blood lymphocytes were found to play an important role in the pathogenesis of amyotrophic leukospongiosis (AL). At early stage of AL they are the sites of reproduction and accumulation of an unconventional virus; they also provide its dissemination in the body of infected animals. In lymph nodes and visceral organs the AL pathogen was detected in much lower quantities and only in the period of clinically manifest disease. The level of the complement was significantly decreased in the serum of animals with experimental AL. This decrease correlated with the development of clinico-morphological lesions and reached its maximum at the terminal stage of disease. PMID- 2904743 TI - Antigenic classification and taxonomy of flaviviruses (family Flaviviridae) emphasizing a universal system for the taxonomy of viruses causing tick-borne encephalitis. AB - For many years the expression "tick-borne encephalitis (TBE) virus" has been used to denote viruses causing the clinical entity TBE. No virus with the name "TBE virus" has been registered in the International Catalogue of Arboviruses, the generally accepted reference for naming arthropod-borne viruses, and no formal agreement has been reached within the scientific community to use the expression "TBE virus"; this term is inaccurate for indicating the etiologic agent of the disease TBE and confuses students and others regarding virus ecology, transmission, and disease severity. This paper suggests alternative names for viruses of the antigenic complex of flaviviruses (family Flaviviridae) to which viruses causing TBE belong. A classification scheme and system of taxonomy for flaviviruses is also proposed. It is suggested that universal acceptance of the term Central European encephalitis virus would improve the dialogue between laboratory virologists and clinicians and improve the understanding of the epidemiology of the tick-borne flaviviruses. PMID- 2904744 TI - Pharmacotherapeutic stature of doxazosin and its role in coronary risk reduction. AB - In hypertension the primary pathophysiologic abnormality is a generalized increase in the peripheral vascular resistance as a result of concentric narrowing of the systemic arterioles, as a result of alpha 1-receptor stimulation. Such stimulation is attenuated by the selective alpha 1-inhibitor doxazosin. The pharmacologic attributes of doxazosin are translated into direct relaxation of the peripheral arteriolar resistance vessels and venous capacitance system, particularly those with a high alpha-adrenoceptor population. The direct effects of such vascular dilatation are immediately beneficial to the heart in reducing systemic and pulmonary vascular pressures that reduce left ventricular wall stress and myocardial oxygen consumption. In clinical studies doxazosin has been found to have a plasma half-life of 19 to 22 hours, of which a single daily dose is sufficient to control hypertension. The antiatherogenic changes in the blood lipid profile resulting from long-term treatment with doxazosin can also be expected to advance its primary prevention potential in hypertensive patients, which is in marked contrast to the potentially disadvantageous changes in the blood lipid profile that follow treatment with beta-blockers and thiazide diuretics. The therapeutic efficacy of doxazosin has been confirmed, irrespective of hypertension severity, age and race of the patient, or the presence of renal impairment or diabetes mellitus. Its side-effect profile is not substantially different from that of placebo or other antihypertensive drug treatment. Given its unique actions regarding antihypertensive efficacy, together with favorable effects on blood lipids, doxazosin probably holds more promise for the prevention of precocious coronary heart disease in hypertensive patients than any other currently available antihypertensive agent. PMID- 2904745 TI - Clinical experience with doxazosin in general medical practice. AB - The antihypertensive efficacy, lipid effects, and safety of doxazosin, a selective alpha 1-inhibitor for the reduction of coronary heart disease (CHD) risk in hypertensive patients, was assessed in a general medical practice setting. Seven hundred seventy-one patients were entered into the study, which involved three phases: (1) a 2-week baseline period, (2) an 8-week period in which patients received doxazosin, 1 to 8 mg once daily, and (3) a 4-week maintenance period. From baseline to final visit there was a highly significant 27% reduction (p less than 0.001) in calculated CHD risk based on the Framingham equation as a consequence of doxazosin's favorable effects on both blood pressure and serum lipid levels. Efficacy and toleration of doxazosin therapy were good to excellent in most patients. The investigators' global assessment of efficacy of once-daily doxazosin therapy was excellent or good for 82% of patients and fair or poor for only 18% of patients. After 12 weeks, 83% of the patients were considered therapy successes (sitting diastolic blood pressure either less than or equal to 90 mm Hg or greater than or equal to 10 mm Hg reduction not reaching less than or equal to 90 mm Hg) at a mean daily dose of 3.5 mg. Seventy-one percent achieved "normalized" blood pressure control (sitting diastolic less than or equal to 90 mm Hg with a decrease of greater than or equal to 5 mm Hg) at a mean dose of 3.1 mg once daily. By the final treatment visit, systolic/diastolic blood pressures of efficacy evaluable patients were reduced by 20.6/15.3 and 21.0/15.4 mm Hg from a mean baseline of 166/104 and 165/104 mm Hg in the sitting and standing positions, respectively (p less than 0.05). Total cholesterol was significantly decreased (p less than 0.01). Most side effects were mild or moderate and disappeared with or were tolerated on continued therapy. The investigators' global assessment of patient toleration of doxazosin treatment was excellent or good for 89% of the 763 patients evaluated and fair or poor for only 11% of patients. The most commonly reported side effects were headache (8%) and dizziness (7%). No clinically significant laboratory changes were apparent, and no trends were observed with regard to organ systems or correlations with dose or duration of treatment. PMID- 2904746 TI - Doxazosin in the treatment of mild and moderate essential hypertension in general medical practice. AB - Doxazosin, a selective alpha 1-inhibitor, was assessed in 34 patients with mild and moderate hypertension. This study involved three phases: (1) a 2-week baseline period, (2) an 8-week period in which patients received 1 to 8 mg of doxazosin once daily, and (3) a 4-week maintenance period. After 12 weeks, 77% of the efficacy evaluable patients were considered therapy successes (sitting diastolic blood pressure either less than or equal to 90 mm Hg with greater than or equal to 5 mm Hg reduction or greater than or equal to 10 mm Hg reduction) at a mean daily dose of 4.3 mg. Sixty-one percent achieved blood pressure control (sitting diastolic blood pressure less than or equal to 90 mm Hg) at a mean dose of 3.7 mg once daily. By the final treatment visit, systolic/diastolic blood pressures of efficacy evaluable patients were reduced by 17/12 and 17/11 mm Hg from a mean baseline of 160/100 and 156/101 mm Hg in the sitting and standing positions, respectively (p less than 0.05). Of the 34 patients, nine (26%) reported 12 adverse experiences, of which only one was severe. No clinically significant laboratory changes were apparent, and no trends were observed with regard to organ systems or correlations with dose or duration of treatment. The investigator's global assessment of efficacy of once-daily doxazosin therapy was excellent or good for 85% of patients and fair for 15% of patients. The investigator's global assessment of toleration was excellent or good for 91% of patients and fair for 9% of patients. The overall lipid profile indicated a decrease in total cholesterol and triglycerides.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2904747 TI - Control of coronary heart disease risk factors with doxazosin as monotherapy and in combination therapy. AB - Although the pathology of essential hypertension is still unclear, studies have shown that doxazosin, a selective alpha 1-inhibitor, is able to effectively control mild-to-moderate hypertension. The aim of these two, noncomparative studies was to evaluate the efficacy and toleration of doxazosin when used as monotherapy and in combination with other antihypertensive agents. In study I, 154 patients with standing and sitting diastolic blood pressures (DBPs) ranging from 95 to 115 mm Hg were treated with once-daily doxazosin (1 to 8 mg) as monotherapy for 12 weeks. Both sitting and standing blood pressures were significantly reduced by doxazosin monotherapy. Target DBP of less than or equal to 90 mm Hg was achieved in 86% of patients after 12 weeks of therapy with doxazosin, and there was no change in heart rate. Cholesterol and triglyceride levels were significantly decreased by doxazosin, but there was no change in glucose levels. Minor side effects were seen in 17.5% of patients, and 2.6% discontinued therapy. In study II, 65 patients with DBPs ranging from 95 to 115 mm Hg on existing antihypertensive therapies were concomitantly treated with doxazosin (1 to 8 mg) once daily for 12 weeks. Target DBPs of less than or equal to 90 mm Hg was achieved in 71% of patients after 12 weeks of therapy with doxazosin. There was no change in heart rate throughout the treatment period, and plasma cholesterol, triglyceride, and glucose levels remained essentially unchanged. Three patients, each receiving a beta-blocker, a diuretic, and doxazosin, were withdrawn because of side effects. Minor side effects, which were considered drug related were seen in 21% of patients. Doxazosin is a drug with good antihypertensive efficacy and is well tolerated as monotherapy and in combination with beta-blockers, thiazide diuretics, angiotensin converting enzyme inhibitors, and various combinations of these drugs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2904748 TI - A multicenter study of doxazosin in the treatment of severe essential hypertension. AB - The antihypertensive efficacy and safety of doxazosin, a selective alpha 1 inhibitor, were assessed in 33 severely hypertensive patients. The study involved three phases: a 1-day baseline period, a 32-day period in which patients received doxazosin, 1 to 16 mg, once daily, and a 4-week maintenance period. All patients were considered therapy successes (sitting diastolic blood pressure either less than or equal to 90 mm Hg or greater than or equal to 10 mm Hg reduction) at a mean daily dose of 8.1 mg. Twenty-seven patients (82%) achieved good blood pressure control (sitting diastolic blood pressure less than or equal to 90 mm Hg) at a mean dose of 6.7 mg once daily. By the final treatment visit, mean systolic/diastolic blood pressures in the sitting and supine positions were significantly reduced by 40/29 and 37/28 mm Hg from a mean baseline of 180/121 and 181/121 mm Hg to final visit values of 140/91 and 144/92 mm Hg, respectively (p less than 0.05). Eleven patients experienced one or more side effects that were mild or moderate and disappeared or were tolerated with continued therapy. During the study no abnormal laboratory test findings were identified by the investigators. The investigators' global assessment of the efficacy and toleration of once-daily doxazosin therapy was excellent or good for 31 (94%) patients and fair for the remaining two patients. PMID- 2904749 TI - Doxazosin in the treatment of patients with mild or moderate hypertension and mild or moderate renal insufficiency. AB - The antihypertensive efficacy and safety of doxazosin, a selective alpha 1 inhibitor, were assessed in 23 hypertensive patients with renal insufficiency. The study involved three phases: (1) a 2-week baseline period, (2) a 10-week period during which patients received doxazosin, 1 to 16 mg, once daily, and (3) a 4-week maintenance period. After 14 weeks of active treatment, systolic/diastolic blood pressures of efficacy evaluable patients were reduced by 8.9/9.2 and 4.6/9.1 mm Hg to final values of 153/90 and 149/91 mm Hg in the supine and standing positions, respectively. The mean dose of the efficacy evaluable patients was 9.8 mg/day. Eleven patients experienced one or more side effects, most of which were mild or moderate and disappeared or were tolerated with continued therapy. No clinically significant laboratory changes were apparent, and no trends were observed with regard to organ systems or correlations with dose or duration of treatment. There were no significant differences in serum creatinine levels between baseline and final visits. The overall lipid profile indicated a decrease in total cholesterol with increases in high-density lipoprotein cholesterol and the high-density lipoprotein/total cholesterol ratio. From baseline to final visit there was a highly significant reduction of 19% (p less than 0.05) in calculated risk scores for coronary heart disease on the basis of the Framingham equation. PMID- 2904750 TI - A single-blind study of doxazosin in the treatment of mild-to-moderate essential hypertensive patients with concomitant noninsulin-dependent diabetes mellitus. AB - Doxazosin, a selective alpha 1-inhibitor, was assessed for antihypertensive efficacy, effect on lipid parameters, and safety profile in 21 hypertensive patients with noninsulin-dependent diabetes mellitus. The study involved a 2- to 4-week baseline period, a 10-week period in which patients received doxazosin, 1 to 8 mg, once daily, and a 4-week maintenance period. All 16 of the efficacy evaluable patients (100%) had their blood pressure controlled (sitting diastolic blood pressure less than or equal to 90 mm Hg) at a mean dose of 3.6 mg once daily. For efficacy evaluable patients mean sitting blood pressure was significantly (p less than 0.05) reduced by 26/17 mm Hg at the final visit. Five patients each reported a single side effect and none was severe. No patients required dose reduction or discontinuation of therapy because of side effects. No clinically significant laboratory changes were apparent, and no trends were observed with regard to organ systems or correlations with dose or duration of treatment. The investigators' global assessment of efficacy of once-daily doxazosin therapy was excellent or good for 15 patients and fair for six patients. The overall assessment of patient toleration was excellent or good for 19 patients, fair for one, and not reported for one. High-density lipoprotein cholesterol was significantly increased (p = 0.03). From baseline to final visit, there was a highly significant reduction of 30% (p less than 0.005) in calculated coronary heart disease risk score on the basis of the Framingham equation. PMID- 2904751 TI - Doxazosin: a newly developed, selective alpha 1-inhibitor in the management of patients with pheochromocytoma. AB - Although surgical removal is the therapy of choice in patients with pheochromocytoma, medical management is necessary in the preoperative preparation of these patients and in inoperable cases. An alpha-adrenoceptor-blocking agent is routinely used as initial therapy to control hypertension, with a beta-blocker used as a second-step agent to control tachycardia when indicated. Doxazosin, a selective alpha 1-inhibitor used as an antihypertensive agent for the reduction of coronary heart disease risk in hypertensive patients, appears to be a good agent to control blood pressure with minimal changes in heart rate. The aim of this study was to assess the antihypertensive efficacy and safety of doxazosin when used alone or in conjunction with a beta-blocker in 24 patients with pheochromocytoma. Overall excellent or good antihypertensive efficacy was assessed by physicians in 19 of 24 patients (79.2%) enrolled in the study. Doxazosin monotherapy was effective in eight of 12 patients (66.7%), and combined therapy with a beta-blocker was effective in 11 of 12 patients (91.7%). The mean pulse rate remained constant throughout therapy. Adverse reactions were minor and transient and occurred in only three patients. Urinary and plasma catecholamine levels tended to decrease or remained unchanged during doxazosin therapy. There were no clinically hazardous abnormalities or problems in hematologic and biochemical laboratory data. Overall, doxazosin was considered very useful or useful in 83.3% of patients. In conclusion, doxazosin appears to be an excellent agent for the management of hypertension associated with pheochromocytoma. PMID- 2904752 TI - Comparison of the effects of doxazosin and atenolol on blood pressure and blood lipids: a one-year, double-blind study in 228 hypertensive patients. AB - The efficacy and toleration of doxazosin and atenolol were compared over a 52 week period in a double-blind, multicenter study of 228 patients with mild-to moderate hypertension. Over the treatment period, both drugs significantly reduced blood pressure, and there were no clinically or statistically significant differences between treatment groups for reductions in standing systolic and diastolic blood pressures or in sitting diastolic blood pressure. However, atenolol treatment caused significantly greater reductions in sitting systolic blood pressure and heart rate. Neither drug significantly affected total serum cholesterol concentrations. Doxazosin treatment lowered serum triglycerides, whereas atenolol treatment produced an increase in serum triglycerides (p less than 0.001, week 30; p less than 0.01, week 50, between treatment groups). Increases in high-density lipoprotein cholesterol and high-density lipoprotein to total cholesterol ratio were obtained with doxazosin treatment, whereas atenolol treatment decreased these lipid fractions (p less than 0.0001, weeks 30 and 50, between treatment groups). Using the Framingham equation, it was calculated that at week 50 the risk of developing coronary heart disease was reduced by 22% for the group taking doxazosin (p less than 0.001 vs baseline) and by 4% (not significant) for patients taking atenolol (p = 0.01, between treatment groups). It is concluded that doxazosin is a well-tolerated and effective antihypertensive drug with a favorable effect on blood lipids. Doxazosin provides an attractive, new alternative first-line drug for the treatment of mild-to-moderate hypertension. PMID- 2904753 TI - Doxazosin versus atenolol: a randomized comparison of calculated coronary heart disease risk reduction. AB - Doxazosin is a selective alpha 1-inhibitor for the reduction of calculated coronary heart disease (CHD) risk in hypertensive patients. Atenolol, although a widely used beta-blocker, appears to adversely affect blood lipids by increasing triglycerides and decreasing high-density lipoprotein (HDL) cholesterol. The aim of our study was to compare doxazosin and atenolol for their therapeutic efficacy in reducing CHD risk (decrease in blood pressure and effect on lipid distribution) and toleration. Patients with mild-to-moderate hypertension were randomized into two groups of 20 patients to receive once-daily atenolol (100 mg) or doxazosin (2 to 8 mg) for 8 weeks. Doxazosin was as effective as atenolol in reducing supine and standing blood pressure. Unlike atenolol, doxazosin did not produce a marked bradycardia. Doxazosin therapy produced favorable modifications in plasma lipid profiles by decreasing triglycerides and total cholesterol and by increasing HDL cholesterol and HDL/total cholesterol ratio. A reverse in this lipid profile was seen with atenolol. Therefore doxazosin may reduce calculated CHD risk more effectively than atenolol, based on the Framingham equation. PMID- 2904754 TI - A comparative study of doxazosin versus atenolol in mild-to-moderate hypertension. AB - Doxazosin, a quinazoline derivative, is a selective alpha 1-inhibitor that reduces calculated coronary heart disease risk by lowering blood pressure while favorably affecting blood lipid levels. The aim of this study was to compare the efficacy and toleration of doxazosin with atenolol, one of the most frequently used cardioselective beta-blockers in Italy. Forty patients with mild-to-moderate hypertension were treated with either atenolol (100 mg) or doxazosin (mean dose, 3.3 mg) once daily for 8 weeks. Both drugs significantly reduced supine and standing systolic and diastolic blood pressures. Atenolol induced marked bradycardia, whereas doxazosin had very little effect on heart rate. Doxazosin produced a favorable effect on blood lipid levels by decreasing triglyceride and total cholesterol levels and increasing high-density lipoprotein cholesterol and high-density lipoprotein total cholesterol ratio. Atenolol had exactly the opposite effect on blood lipid levels. Both drugs had equivalent toleration profiles. It was concluded that doxazosin was as effective as atenolol in reducing elevated supine and standing blood pressures. In addition, doxazosin had a beneficial effect on lipid profiles and minimal effect on heart rate. Therefore doxazosin may reduce calculated coronary heart disease risk in hypertensive patients. PMID- 2904755 TI - A double-blind comparative study of doxazosin and nitrendipine in patients with mild-to-moderate essential hypertension. AB - The antihypertensive efficacy and safety of doxazosin, a selective alpha 1 inhibitor, were compared with nitrendipine. Seventy-two hypertensive patients were entered into the 18-week, double-blind parallel group study, which involved three phases: a 4-week baseline period, a 10-week period in which patients received 1 to 8 mg of doxazosin or 10 and 20 mg of nitrendipine once daily, and a 4-week maintenance period. For all patients, the mean final daily doses were 2.5 mg for doxazosin and 13.9 mg for nitrendipine. In efficacy evaluable patients the percentages of therapy successes (standing diastolic blood pressure less than or equal to 90 mm Hg with greater than or equal to 5 mm Hg reduction or greater than or equal to 10 mm Hg decrease) were comparable for doxazosin (94%) and nitrendipine (91%), as was the proportion in whom blood pressure was "normalized" (standing diastolic blood pressure less than or equal to 90 mm Hg), 91% and 85, respectively. Blood pressures (diastolic and systolic in supine and standing positions) were significantly reduced (p less than 0.05) at all visits in both treatment groups. Ten patients (28%) in each treatment group experienced at least one adverse event. No clinically significant laboratory changes were apparent in either the doxazosin or nitrendipine groups, and no trends were observed with regard to organ systems or correlations with dose or duration of treatments. The investigators' global assessment of efficacy was rated excellent or good for all doxazosin-treated patients and excellent or good for 32 and fair for four in the nitrendipine group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2904756 TI - The addition of doxazosin to the treatment regimen of hypertensive patients not responsive to nifedipine. AB - The efficacy and safety of doxazosin, a selective alpha 1-inhibitor, were assessed in hypertensive patients who failed to respond to nifedipine. Fifty patients were entered into a study that involved three phases: (1) a 2-week baseline period, (2) a 10-week period in which patients received doxazosin, 1 to 8 mg, once daily, and (3) a 4-week maintenance period. After 14 weeks, all 43 efficacy evaluable patients were considered therapy successes (sitting diastolic blood pressure either less than or equal to 90 mm Hg or greater than or equal to 10 mm Hg reduction) at a mean daily dose of 3.1 mg. Ninety-three percent achieved blood pressure control (sitting diastolic blood pressure less than or equal to 90 mm Hg) at a mean dose of 3.1 mg once daily. By the final treatment visit, sitting systolic and diastolic blood pressures of efficacy evaluable patients were reduced (p less than 0.05) by 16/18 mm Hg from a mean baseline of 157/103 mm Hg to a final value of 141/85 mm Hg. The most prevalent side effect was vertigo (six patients). Most side effects were mild or moderate and disappeared or were tolerated with continued therapy. No clinically significant laboratory changes were apparent, and no trends were observed with regard to organ systems or correlations with dose or duration of treatment. The investigators' global assessment was excellent or good for 98% of patients for both efficacy and toleration. From baseline to final visit there was a highly significant reduction of 17% (p less than 0.001) in the calculated coronary heart disease risk score, which was based on the Framingham equation. PMID- 2904757 TI - A comparison of doxazosin and enalapril in the treatment of mild and moderate essential hypertension. AB - The antihypertensive efficacy and safety of doxazosin, a selective alpha 1 adrenoceptor antagonist, were compared with that of the angiotensin-converting enzyme inhibitor enalapril in an 18-week double-blind, parallel-group trial. Sixty-seven hypertensive patients entered the three-phase study, which involved a 4-week placebo washout period, a 10-week titration period with doxazosin, 1 to 16 mg, or enalapril, 10 to 40 mg once daily followed by a 4-week maintenance period. The target response was a standing diastolic blood pressure less than or equal to 90 mm Hg. In the 62 efficacy evaluable patients the mean final daily dose of doxazosin was 5.6 mg and 25.5 mg for enalapril. The percentages of therapeutic successes were 74% in the doxazosin- and 81% in the enalapril-treated groups; the proportions in whom standing diastolic blood pressure less than or equal to 90 mm Hg were 55% and 61%, respectively. Both sitting and standing blood pressures were significantly reduced at all visits during the 14-week treatment period in both groups. Twelve patients receiving doxazosin reported 14 adverse events and nine patients administered enalapril reported 19 adverse events; therapy was stopped in three patients in each group because of side effects. The overall assessment of efficacy was excellent or good for 71% of the doxazosin-treated and 67% of the enalapril-treated patients, respectively. Toleration of therapy was excellent or good for 91% of the doxazosin-treated and 88% of the enalapril-treated patients, respectively. No clinically significant changes were observed in the serum lipids, plasma biochemistry, or hematologic profiles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2904758 TI - A single-blind study of doxazosin in the treatment of essential hypertension when added to nonresponders to angiotensin-converting enzyme inhibitor therapy. AB - Doxazosin, a selective alpha 1-inhibitor, was assessed in hypertensive patients with sitting diastolic blood pressures (DBPs) of 95 to 114 mm Hg while receiving a stable dose of captopril or enalapril. Fifty-six patients were entered into the study that involved three phases: (1) a 2-week baseline period, (2) a 10-week period in which patients received doxazosin, 1 to 8 mg, once daily, and (3) a 4 week maintenance period. After 14 weeks of doxazosin treatment, 95% of the patients were therapy successes (sitting DBP either less than or equal to 90 mm Hg with greater than or equal to 5 mm Hg reduction or greater than or equal to 10 mm Hg reduction) at a mean daily dose of 2.4 mg. Ninety-three percent achieved blood pressure control (sitting DBP less than or equal to 90 mm Hg) at a mean dose of 2.3 mg once daily. By the final treatment visit, systolic/diastolic sitting blood pressures for efficacy evaluable patients were reduced by 16/17 mm Hg from a mean baseline of 158/101 mm Hg to a final value of 143/84 mm Hg. Throughout the study (2 to 14 weeks), all blood pressure reductions from baseline were significant (p less than 0.05). There was only one side effect (vertigo) that warranted dose reduction, and only one patient was withdrawn from therapy (nausea). Most side effects were mild or moderate and disappeared or were tolerated with continued therapy. No clinically significant laboratory changes were apparent, and no trends were observed with regard to organ systems or correlations with dose or duration of treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2904759 TI - Implications of doxazosin therapy on risk of coronary heart disease. AB - Antihypertensive treatment is known to reduce mortality in severe hypertension and cardiovascular morbidity in mild and moderately severe hypertension, for example, from stroke and left ventricular failure. However, treated hypertensive patients still have significantly higher mortality and morbidity than matched control subjects. In particular, risk of coronary heart disease is affected little by antihypertensive treatment. There may be several explanations for these less than optimal results. For example, blood pressure may not have been brought down to strictly normotensive levels or an antihypertensive agent, which adversely affects serum lipoproteins, may have been used, thereby offsetting the intended therapeutic effect. Doxazosin, a new selective alpha 1-inhibitor, offers both effective antihypertensive action and a favorable lipid effect. Both of these effects could have a positive impact on risk of coronary heart disease and therefore may prove to be more effective than previously used antihypertensive treatments. PMID- 2904760 TI - Class II human leukocyte antigen genes and T cell receptor polymorphisms in patients with rheumatoid arthritis. AB - Human leukocyte antigen (HLA) typing was performed in 174 patients with rheumatoid arthritis and 222 white control subjects. Increases in HLA-DR4 and HLA DR1 were observed as in previous studies. Each of these appeared to be inherited as dominant risk factors. Southern blotting with a DR-beta probe after digestion of genomic DNA with the restriction enzyme Bam HI showed seven bands. Three of them correlated with DR4 and were increased in rheumatoid arthritis patients. Subsets of DR4 were determined by polymerase chain reaction amplification followed by hybridization with oligonucleotide probes. Dw4 was increased in rheumatoid arthritis patients, and the frequency of the other subsets appeared to be similar in rheumatoid arthritis patients and control subjects. A polymorphism associated with the T cell receptor V-beta-8 gene family was significantly increased in rheumatoid arthritis patients. PMID- 2904761 TI - Molecular genetic studies of rheumatoid arthritis. AB - Bam HI DR-beta and DQ-beta restriction fragment length polymorphisms (RFLPs) were found with increased frequency in white persons with seropositive rheumatoid arthritis as compared with control subjects. DR-beta 4.8-, 5.2-, and 7.0-kilobase (kb) RFLPs were observed in 86.5 percent of rheumatoid arthritis patients and in 56 percent of control subjects (p = 0.001, relative risk [RR] = 5.0). The 6.0-kb RFLP was present in 79 percent of rheumatoid arthritis patients and 32 percent of control subjects (p = 0.0002, RR = 8.0). The 4.8-, 5.2-, and 7.0-kb RFLPs correlated with DR4, -7, -9, and -w53 phenotypes and the 6.0-kb RFLP correlated only with DR4. Thus, these RFLPs do not appear to be disease-specific. A DQ-beta 3.2-kb RFLP was found in 63.5 percent of rheumatoid arthritis patients and in 38.0 percent of control subjects (p = 0.01, RR = 2.8). This fragment was frequently found in persons expressing DR1 and DQw1 phenotypes. Probes consisting of the first exon of the DR-beta-I and DR-beta-IV genes, respectively, only hybridized with the 5.2- and 6.0-kb RFLPs. These data suggest that more than one gene within the major histocompatibility complex contributes to susceptibility to seropositive rheumatoid arthritis in white persons. PMID- 2904762 TI - Major histocompatibility complex associations with systemic lupus erythematosus. AB - This study focused on clinical subsets within systemic lupus erythematosus (SLE) in order to identify more homogeneous patient groups in which to define disease susceptibility gene(s). Analysis of the major histocompatibility complex gene products and genes with major histocompatibility complex class II and class III locus-specific probes and oligonucleotide probes for selected human leukocyte antigen DQ-beta alleles showed significant increases of human leukocyte antigen DR2 and the rare DQ-beta allele DR2-DQw1.AZH in the lupus nephritis patients compared with lupus patients without renal disease (relative risk = 8.3). C4A null was detected in one third of all of the SLE patients. In two thirds of the C4A null patients this was due to a DR3-associated C4A gene deletion. The remaining third may have a regulatory defect and this was DR2-associated. DR4 was significantly decreased in the nephritis patients in comparison with the non renal SLE patients (relative risk = 0.3). A novel DQ-beta gene has been sequenced from two SLE patients that has not been observed in the normal population. Potential implications of these findings are discussed. PMID- 2904763 TI - Restriction fragment length polymorphism analysis in ankylosing spondylitis. AB - We utilized the technique of restriction fragment length polymorphism (RFLP) analysis in order to examine class I major histocompatibility complex genes in 52 Alabama ankylosing spondylitis patients and 107 local control subjects. A 9.2 kilobase PvuII RFLP was identified using the class I-specific B7 cDNA probe pDP001 that was closely associated with ankylosing spondylitis, most specifically with peripheral joint (including shoulder and hip) involvement. This fragment is associated with human leukocyte antigen A3 and A9 alleles, and segregation analysis in 11 multiplex families showed the RFLP to frequently segregate independently of B27 haplotypes. Two more recent studies have not confirmed the association of the 9.2-kilobase PvuII RFLP with ankylosing spondylitis per se, believed to be due to clinical and possibly genetic differences between the patient groups studied. These data strongly suggest at least one other major histocompatibility complex class I gene to be operative in predisposition to or modification of ankylosing spondylitis. PMID- 2904764 TI - Studies of HLA-B27-associated disease. AB - Several rheumatic diseases were first shown to be associated with human leukocytic antigen (HLA)-B27 in 1973. Recent developments in understanding this association include the finding that there are at least six variants of HLA-B27 at the molecular level, with no one variant preferentially associated with disease. Detailed studies of the structure of the HLA-B27 molecular family are in progress in several laboratories. Mice expressing HLA-B27 and transmitting it to their offspring (transgenic mice) have been produced and are being studied for their response to bacteria that are known to trigger reactive arthritis in B27+ humans. A particular restriction fragment length polymorphism was recently claimed to be a genetic marker for an additional risk factor in ankylosing spondylitis, but two other laboratories have failed to confirm this finding. PMID- 2904765 TI - Nonadrenergic sympathetic neural influences on basal pancreatic hormone secretion. AB - Evidence for peptidergic innervation of the islets of Langerhans is increasing, yet the role of neuropeptides in mediating neurally induced changes of islet function is not clear. To determine if nonadrenergic transmitters make an important contribution to sympathetic neural effects on basal pancreatic hormone secretion, we examined the effect of local sympathetic nerve stimulation (SNS) on the output of immunoreactive insulin (IRI), immunoreactive glucagon (IRG), and somatostatin (SLI) from the duodenal lobe of the pancreas in situ in halothane anesthetized dogs, under conditions where the actions of the classical transmitter norepinephrine (NE) should be blocked by propranolol (PROP) and yohimbine (YO). In the absence of adrenergic antagonists, SNS rapidly reduced the output of IRI (delta = -1.34 +/- 0.91 mU/min) and SLI (delta = -600 +/- 350 fmol/min) and stimulated that of IRG (delta = +1.39 +/- 0.57 ng/min). In the presence of PROP and YO, SNS induced similar changes of hormone secretion: delta IRI, -1.30 +/- 0.53 mU/min; delta SLI, -480 +/- 180 fmol/min; delta IRG = +1.89 +/- 0.63 ng/min. Because PROP and YO abolished the pancreatic effects of high dose infusions of NE (1 microgram.kg-1.min-1 iv), we suggest that the antagonists produced sufficient, combined adrenergic blockade at the level of the islet, and we conclude that a nonadrenergic neurotransmitter or modulator plays a major role in mediating sympathetic neural effects on basal islet hormone secretion. PMID- 2904766 TI - GHRF causes biphasic stimulation of SRIF secretion from rat hypothalamic cells. AB - The complex interactions of the hypothalamic releasing peptides somatostatin (SRIF) and growth hormone (GH)-releasing hormone (GHRF), which regulate GH secretion, are still incompletely understood. To further scrutinize these interactions, we have studied the effects of GHRF on SRIF secretion from dispersed adult rat hypothalamic cells. Rat GHRF caused calcium- and dose dependent stimulation of SRIF release in static 1-h incubations. SRIF release was stimulated by GHRF in a concentration range of 1-100 nM. However, the extended dose-response curve was biphasic in nature, with a significantly lower SRIF response in the presence of 1 microM GHRF vs. 100 nM GHRF. SRIF release, stimulated by another secretagogue (10 microM veratridine), was not affected by the presence or absence of 1 microM GHRF, suggesting the lack of toxic impairment of hypothalamic cell function by GHRF at this concentration. In conclusion, a biphasic stimulatory pattern of SRIF secretion in response to GHRF was observed in experiments employing dispersed rat hypothalamic cells. The biphasic SRIF response pattern to GHRF may be relevant in the physiological regulation of GH secretion. PMID- 2904767 TI - Relative contributions of the nervous system and hormones to CNS-mediated hyperglycemia. AB - We quantitatively determined the relative contributions of hormonal factors and the nervous system to the total glucose response after stimulation of the cholinergic neurons in the central nervous system of fed rats. Hepatic venous plasma glucose, glucagon, insulin, epinephrine, and norepinephrine were measured during 120 min after injection of neostigmine (5 X 10(-8) mol) into the third cerebral ventricle in rats subjected to bilateral adrenodemedullation (ADMX) to prevent epinephrine secretion (observed insulin secretion), with and without intravenous infusion of somatostatin to prevent glucagon and insulin secretion. Injection of neostigmine in intact rats resulted in increases in glucose, glucagon, epinephrine, and norepinephrine. Comparison of glucose areas suggests that 22% of the hyperglycemic response is due to the glucagon effect, that 29% is due to the epinephrine effect, and that an unknown factor other than epinephrine or glucagon, which may include activation through direct neural innervation of the liver via alpha-adrenergic receptor, contributes 49%. The suppressive effect of epinephrine on insulin secretion, which is potentially stimulated by direct neural activation of the pancreas, contributes 18% of the net hyperglycemia. PMID- 2904768 TI - Time-dependent involvement of autonomic nervous system in hyperglycemia due to 2 deoxy-D-glucose. AB - To determine the mechanism of time-dependent hyperglycemia due to intracranial injection of 2-deoxy-D-glucose (2DG), we examined the effects of various blockers of the autonomic nervous system on the hyperglycemia and hyperglucagonemia induced by intracranial injection of 2DG in male Wistar rats in light and dark periods. Hexamethonium inhibited the hyperglycemia in both light and dark periods but did not block the hyperglucagonemia in either period. Intracranial injection of 2DG did not affect the plasma insulin concentration in saline-treated control rats, but hexamethonium caused an increase in the basal plasma insulin concentration and further increase in the plasma concentration after 2DG injection in the light period. Phenoxybenzamine, an alpha-adrenergic blocker, inhibited the hyperglycemia only in the light period and the hyperglucagonemia only in the dark period and slightly stimulated the basal concentrations of insulin and glucagon only in the light period. Propranolol, a beta-adrenergic blocker, blocked the hyperglycemia and hyperglucagonemia and also lowered the basal plasma glucagon concentration in both periods. Atropine sulfate and atropine methyl nitrate, muscarinic blockers, inhibited hyperglycemia only in the light and dark period, respectively. In contrast, both drugs blocked the hyperglucagonemia in both periods. These findings suggest that the autonomic nervous system is involved time dependently in the hyperglycemia and hyperglucagonemia due to intracranial 2DG injection. PMID- 2904769 TI - Patterns of fast synaptic cholinergic activation of neurons in the celiac ganglia of cats. AB - Fast nicotinic transmission was studied in vitro in neurons of isolated cat celiac ganglia. In the absence of nerve stimulation, neurons could be classified into three types: silent neurons, synaptically activated neurons, and spontaneously discharging neurons. In all three types, fast synaptic activation could be obtained in single neurons by stimulating with a single pulse both the splanchnic nerves or one of the peripheral nerves connected to the ganglia. During repetitive nerve stimulation, a gradual depression of the central and peripheral fast nicotinic activation occurred, which was not affected by phentolamine plus propranolol, domperidone, atropine, or naloxone. Repetitive nerve stimulation was followed by a long lasting discharge of excitatory postsynaptic potentials and action potentials that decreased gradually with time. This discharge, which was probably due to presynaptic or prejunctional facilitation of acetylcholine release from cholinergic terminals, was reduced by the application of phentolamine plus propranolol, domperidone, or atropine and increased with naloxone. The existence of the mechanisms described in this study reflects the complexity of the integrative processes at work in neurons of the cat celiac ganglia that involve fast synaptic cholinergic activation. PMID- 2904770 TI - Effect of prostaglandin E2 on rabbit colonic smooth muscle cell contraction. AB - Isolated circular smooth muscle cells from the rabbit distal colon were used to study the effect of prostaglandin E2 (PGE2) on bethanechol-stimulated smooth muscle cell contraction. Contraction was expressed as the percentage decrease in mean cell length compared with unstimulated cells. Incubation with different concentrations of PGE2 (10(-10)-10(-6) M) did not cause contraction or relaxation of unstimulated smooth muscle cells. Bethanechol stimulated a dose-dependent contraction that was maximal at 30 s. The threshold for bethanechol-stimulated contraction was 10(-11) M; the ED50 was 10(-10) M; and the maximum contraction (23.0 +/- 1.8%) occurred at 10(-8) M. Preincubation with PGE2 reduced both the efficacy and potency of bethanechol-stimulated contraction. Preincubation with 8 bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP) or dibutyryl-cAMP reduced the efficacy of bethanechol-stimulated contraction without affecting potency. Increasing concentrations of PGE2 stimulated a dose-dependent increase in the production of intracellular cAMP (P less than 0.05). These studies show that PGE2 inhibits bethanechol-stimulated contraction of isolated colonic circular myocytes and is associated with increased production of intracellular cAMP. There is also a cAMP-independent effect of PGE2 on the potency of bethanechol stimulation. PMID- 2904771 TI - Tonic inhibition of renal response to vasopressin by a pertussis toxin substrate. AB - The putative role of the inhibitory guanine nucleotide binding protein (Gi) in modulating the renal response to vasopressin was investigated using islet activating protein (IAP). IAP treatment in rats in vivo abolished the capacity of alpha 2-adrenoceptors to reverse vasopressin-induced adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in microdissected cortical collecting tubule (CCT) segments. IAP pretreatment also caused a marked upward shift in the dose response curve of vasopressin (10(-10) to 10(-4) M)-induced cAMP accumulation. Augmentation of the response to vasopressin in rat CCT was dependent on the in vivo dose of IAP and paralleled the loss in alpha 2-adrenoceptor responsiveness. In the isolated perfused kidney the antinatriuretic and antidiuretic effects of the V2-receptor agonist desamino-8-D-arginine vasopressin (DDAVP) (1 pM) were enhanced following IAP pretreatment. alpha 2-Adrenoceptor stimulation (30 nM epinephrine) inhibited the renal effects of DDAVP (1 pM) in kidneys from control but not IAP-pretreated rats. Interestingly, IAP pretreatment alone caused increased urine flow rate and enhanced excretion of sodium and chloride without affecting potassium excretion or renal hemodynamics in vitro. Our results suggest that an IAP substrate, probably Gi, 1) is required for signal transduction by renal alpha 2-adrenoceptors, 2) may tonically modulate the response to vasopressin in the CCT but not of parathyroid hormone in the proximal convoluted tubule, and 3) participates in renal water and electrolyte reabsorption independent of exogenous adenylate cyclase stimulation. PMID- 2904772 TI - Alpha-adrenergic vasoconstriction and receptor subtypes in large coronary arteries of calves. AB - We investigated alpha-adrenoceptor subtype distribution in large coronary arteries from both functional and biochemical perspectives. The effects of intracoronary administration of the selective alpha 1-adrenoceptor agonist phenylephrine (0.1-5.0 micrograms/kg ic), of the selective alpha 2-adrenoceptor agonist B-HT 920 (0.1-5.0 micrograms/kg ic), and of the mixed alpha 1 + 2 adrenoceptor agonist norepinephrine (0.01-0.5 micrograms/kg ic) were examined on measurements of left circumflex coronary artery diameter in conscious calves. After beta-adrenergic blockade, equivalent reductions in large coronary artery diameter were observed with phenylephrine (-6.9 +/- 0.7%), B-HT (-5.9 +/- 0.5%), and norepinephrine (-6.0 +/- 0.4%). Phenylephrine-induced constrictions were abolished by prazosin, an alpha 1-selective antagonist, but unaffected by rauwolscine, an alpha 2-selective antagonist. Conversely, the B-HT-induced constriction was abolished by rauwolscine but unaffected by prazosin. Coronary constriction with norepinephrine was attenuated with either prazosin or rauwolscine and abolished by the two antagonists combined. Ligand-binding studies in which [3H]prazosin and [3H]rauwolscine and sarcolemmal membranes were used revealed an alpha 1-adrenoceptor density of 15 +/- 3.1 fmol/mg protein with a dissociation constant (KD) of 0.7 +/- 0.2 nM and an alpha 2-adrenoceptor density of 68 +/- 5.1 fmol/mg protein, with a KD of 7.4 +/- 1.2 nM. Thus large coronary arteries of the calf contain both alpha 1- and alpha 2-adrenoceptor subtypes, each of which elicits constriction of the large coronary artery in the conscious animal. PMID- 2904774 TI - Blockade of spinal pathways decreases pre- and postganglionic discharge differentially. AB - Although discharge of many sympathetic nerves decreases substantially on transection of the spinal cord in cats, firing of splenic and mesenteric postganglionic nerves continues unabated (R. L. Meckler and L. C. Weaver, Brain Res. 338: 123-135, 1985; R. D. Stein and L. C. Weaver. J. Physiol. Lond. 396: 155 172, 1988). Therefore, ongoing sympathetic outflow directed to the splanchnic circulation was proposed to be less dependent on supraspinal excitatory drive than that directed to other vascular beds. Blockade or transection of cervical spinal pathways in chloralose-anesthetized cats significantly decreased firing of gastric, hepatic, adrenal, and lumbar chain sympathetic nerves. Discharge of gastric and hepatic nerves decreased as much as that of adrenal and lumbar chain nerves; therefore, sustained discharge in the absence of bulbospinal excitation is not a characteristic of all sympathetic nerves innervating the splanchnic circulation. In contrast, discharge of the preganglionic greater splanchnic nerves was not decreased after spinal transection, although it changed from a rhythmic to an asynchronous pattern. This provocative finding suggests that rhythmicity of preganglionic discharge may be important for effective synaptic transmission to some postganglionic neurons, since postganglionic gastric, hepatic, and adrenal nerve firing decreased in the presence of sustained but asynchronous preganglionic input. PMID- 2904773 TI - Regulation of [3H]GABA release from strips of guinea pig urinary bladder. AB - The presence of receptors that regulate the release of gamma-aminobutyric acid (GABA) was studied in strips of the guinea pig urinary bladder. GABA (10(-8)-10( 5) M) and muscimol (10(-8)-10(-5) M), but not baclofen (10(-5) M), reduced the Ca2+-dependent, tetrodotoxin-resistant release of [3H]GABA evoked by high K+ from the urinary bladder strips preloaded with [3H]GABA. The inhibitory effect of muscimol was antagonized by bicuculline and potentiated by diazepam, clonazepam, and pentobarbital sodium. The potentiating effect of clonazepam was antagonized by Ro 15-1788. Acetylcholine (ACh) inhibited the high K+-evoked release of [3H]GABA. The inhibitory effect of ACh was antagonized by atropine sulfate and pirenzepine but not by hexamethonium. Norepinephrine (NE) inhibited the evoked release of [3H]GABA. The inhibitory effect of NE was mimicked by clonidine, but not by phenylephrine, and was antagonized by yohimbine but not by prazosin. These results provide evidence that the release of GABA from strips of guinea pig urinary bladder is regulated via the bicuculline-sensitive GABAA receptor, M1 muscarinic, and alpha 2-adrenergic receptors. PMID- 2904776 TI - Double-blind comparison of loratadine (SCH 29851), astemizole, and placebo in hay fever with special regard to onset of action. AB - In this double-blind study, 65 patients with hay fever were treated for 14 days with either loratadine 10 mg once daily, astemizole 10 mg once daily, or placebo. On the third day of treatment loratadine was statistically superior to placebo, but astemizole and placebo showed no significant differences according to the ratings for symptomatology, efficacy, and individual symptoms. Adverse effects were minimal and did not differ between the three groups. Loratadine had a significantly earlier onset of action than astemizole with comparable efficacy and safety. PMID- 2904775 TI - Effects of cimaterol, a beta-adrenergic agonist, on energy metabolism in ob/ob mice. AB - Cimaterol when added to the diets for 3 or 9 wk stimulated whole animal energy expenditure and brown adipose tissue thermogenic activity comparably in genetically obese (ob/ob) and lean mice; however, ob/ob mice fed diets containing 140 or 280 micrograms cimaterol/kcal failed to increase energy intake as much as lean mice. Consequently, the efficiency of energy retention was actually lower in ob/ob mice fed diets containing cimaterol than in similarly treated lean mice. Cimaterol stimulated skeletal muscle gain in ob/ob mice, although at no point did final hindlimb muscle weight of ob/ob mice equal that of lean mice. Hyperinsulinemia was abolished in ob/ob mice fed diets containing cimaterol even though plasma corticosterone concentrations remained elevated. We conclude that cimaterol has greater effects on energy balance and plasma insulin, but not on skeletal muscle accretion, in ob/ob mice than in lean mice. PMID- 2904777 TI - Controversies in pulmonary medicine. Patients with COPD should be started initially on anticholinergic bronchodilators. PMID- 2904778 TI - Attenuation of bronchofiberscopy-induced cough by an inhaled beta 2-adrenergic agonist, fenoterol. AB - We investigated the antitussive effect of fenoterol in 40 patients (34 males) undergoing bronchofiberscopy for diagnostic purposes. The patients were randomly allocated into two groups, one receiving two puffs (400 micrograms) of fenoterol and the other two puffs of placebo, from a metered-dose inhaler in a double-blind fashion. The following procedure was used: premedication with 0.5 mg atropine sulfate and 100 mg hydroxyzine administered intramuscularly; 50 min later, aerosol administration; 10 min after aerosol administration, a standardized topical anesthesia was performed. As soon as the bronchofiberscope had entered the trachea, sounds were recorded for a 5-min period, while the tracheobronchial tree was systematically inspected. Additional lidocaine (2% solution, 2 ml boluses) was injected into the airways if troublesome cough occurred. The two groups did not differ significantly in terms of age, sex ratio, and smoking history. In contrast, both the number of coughs and the volume (ml) of additional lidocaine were significantly smaller in the fenoterol group than in the placebo group: m +/- SEM: 35.0 +/- 5.5 versus 51.6 +/- 6.5, p less than 0.01 and 1.9 +/- 0.5 versus 3.3 +/- 0.4, p less than 0.01, respectively. Thus, fenoterol exhibits antitussive properties and can usefully be administered before bronchofiberscopy. PMID- 2904779 TI - Bacterial adherence. Adhesin receptor-mediated attachment of pathogenic bacteria to mucosal surfaces. AB - Pathogenic bacteria adhere to and colonize mucosal surfaces of the susceptible host in a highly selective manner. After the organisms penetrate the nonspecific mechanical and cleansing forces, ligands (or adhesins) on the surface of the bacteria interact in a lock-and-key fashion with complementary receptors on mucosal surfaces of the host. The adhesins are usually composed of proteins in the form of fimbriae or fibrillae and the receptors of glycolipids or glycoproteins. At the epithelial cell surfaces, two classic examples of bacterial adherence are the lipoteichoic acid-mediated attachments of group A streptococcal and the type 1 fimbriae-mediated attachment of Escherichia coli. In group A streptococci, the adhesin, lipoteichoic acid (LTA), is anchored to a protein(s) on the surface of the bacterial cells and interacts through its lipid moiety with fibronectin molecules deposited on and bound to the epithelial cells. In type 1 fimbriated E. coli, a minor 29-kDa protein located at the tip of the fimbriae interacts with D-mannose residues of glycoprotein receptors on host cells. Similar adhesin-receptor interactions have now been described for a number of pathogenic microbial agents, and undoubtedly play a central role in the early steps of the infectious process. PMID- 2904780 TI - [Vesical neuropathy in systemic vasculitis: 3 cases]. AB - Bladder neuropathy was diagnosed in 3 patients with systemic vasculitis (temporal arteritis: 1 case; periarteritis nodosa: 2 cases). Clinical characteristics were: dysuria, diminished or abolished bladder sensation leading to indolent bladder retention. Urodynamic investigation showed hypotonic and underactive detrusor, increased detrusor compliance, hyposensitive bladder, and/or overactive urethral closure. Needle electrode examination showed signs of denervation of periurethral muscles; sacral evoked latencies were increased, favouring pudenal nerve alterations. Symptoms and urodynamic abnormalities resolved following corticosteroid therapy. Clinical and therapeutic implications of bladder neuropathy in necrotizing vasculitis are emphasized. PMID- 2904781 TI - [The role of infection in the precipitation of periarteritis nodosa]. AB - Circulating immune complexes are thought to play an essential part in the pathogenesis of necrosing angiitis. This theory also allows a role to be attributed to certain infectious agents (viral, bacterial, parasitic) in the development of periarteritis nodosa (PAN). An infectious syndrome was found in all our 9 patients, aged 26 to 69 years, with histologically confirmed PAN: previous infection (over 15 days before hospital admission): otitis, hepatitis B, tonsillitis, ascaris (Case n.7), pulmonary tuberculosis, brucellosis, seropositivity for Chlamydia trachomatis (Case n.9), paratyphoid (Case n.5), seropositivity for Yersiniosis pseudo-tuberculosis (Case n.2), seropositivity for Chlamydia trachomatis (Cases 3 and 4), seropositivity for toxoplasmosis (Cases 4 and 6), seropositivity for rubella (Case n.8). Recent infection (less than 15 days before hospital admission): staphylococcus aureus septicaemia (Case n.1); Group A betahemolytic streptococcal urinary infection (Case n.2); Group A betahemolytic streptococcal otitis media; pseudomonas aeruginosa and Klebsiella septicaemia; enterococcal cystitis (Case n.4); progressive pulmonary tuberculosis (Case n.6), acinetobacter pneumonia (Case n.9). The HBs antigen was only found in one patient (Case n.6), who had an active hepatitis. PMID- 2904782 TI - Cocaine-induced behavioral sensitization and kindling: implications for the emergence of psychopathology and seizures. PMID- 2904783 TI - Plasma homovanillic acid as an index of central dopaminergic activity: studies in schizophrenic patients. AB - Despite the limitations of the dopamine hypothesis, compelling evidence remains that implicates dysfunction of CNS dopamine systems in the pathophysiology of schizophrenia. The longitudinal measurement of levels of plasma HVA has proved a useful tool in studying neuroleptic effects and has highlighted time-dependent effects as a potentially important facet of the mechanism of antipsychotic action of these drugs. Despite the good clinical correlates of plasma HVA levels, caution is needed in interpreting plasma levels of HVA with regard to CNS dopamine activity. The peripheral nervous system significantly contributes to levels of HVA that circulate in plasma. This issue is underscored by the fact that CSF HVA shows different neuroleptic response patterns than that seen in plasma. The administration of a peripherally acting MAO inhibitor to enhance the CNS "signal" in circulating levels of HVA does not resolve the "problem" of different CSF-plasma HVA neuroleptic response patterns. The possibility that mesocortical dopamine activity is reflected by CSF HVA is suggested by indirect evidence from clinical and preclinical studies. Future studies in which attempts are made at using both plasma and CSF HVA to enhance neurochemical and clinical correlates may help to advance our understanding of the contributions of specific CNS dopamine systems to schizophrenia. PMID- 2904784 TI - Neuroleptic binding to human brain receptors: relation to clinical effects. AB - Table 2 summarizes the potential clinical consequences of neurotransmitter receptor blockade by neuroleptics. These pharmacological effects of neuroleptics at receptors in brain and elsewhere in the body are likely responsible for therapeutic and certain adverse effects as well as some drug-drug interactions. Data presented here should allow the physician a rational basis for selecting neuroleptics to minimize these unwanted effects in patients. PMID- 2904785 TI - Dopamine neuronal tracts in schizophrenia: their pharmacology and in vivo glucose metabolism. PMID- 2904786 TI - Effects of acute and chronic neuroleptic treatment on the activity of midbrain dopamine neurons. AB - The preceding data suggest that the primary effect of repeated AD administration on most midbrain DA neurons is inactivation. This depolarization-induced cessation of spontaneous activity would appear to have a marked effect on both basal and stimulated DA release from nerve terminals in that several studies, using voltametric techniques, have now demonstrated DA release to be diminished under these conditions. These findings stand in marked contrast to the acute effects of ADs where biochemical techniques have been used to demonstrate a marked increase in the release of DA into projection areas. The combined effects of acute and repeated AD administration on midbrain DA cell activity may explain the delay in onset of both their therapeutic and neurological side effects. PMID- 2904787 TI - [Management of a subject with HIV positive serology]. PMID- 2904788 TI - [Skin diseases caused by cold]. PMID- 2904789 TI - [Selective control of different hypophysial secretions by long-lasting pharmacodynamic agents. Analogs of somatostatin and LHRH and long-lasting bromocriptine]. AB - The biological activity of the natural somatostatin can be quantitatively and qualitatively altered by the substitution and/or the exclusion of some of its amino-acids. The most used synthetic analog, SMS 201-995, has a potent inhibiting effect on GH secretion, but is less effective on insulin and glucagon secretions. It is mainly used in Endocrinology for the treatment of acromegaly. It is also useful for inhibiting the inappropriate TSH secretion from a thyrotroph adenoma. The LH-RH agonists ast essentially by desensitizing the gonadotroph from the endogenous LH-RH. By sub-cutaneous, intra-muscular or nasal route, they allow to inhibit the gonadal functions in some hormone-dependent cancers and in true precocious puberty. More recently, they have been tested for the treatment of gonadotropic adenomas, where they may have sometimes a paradoxical effect. In combination with exogenous gonadotropins, they enhance the control of ovulation and are new valuable tools for IVF programs. Clinical studies with the LH-RH antagonists are just beginning. The long-acting bromocriptine affords a new alternative to the oral treatment of hyperprolactinaemia. Its suppressive effects lasts at least 35 days in normal subjects and 21 days in patients with macroprolactinomas. PMID- 2904790 TI - [Urinate more, with less alpha blockaders]. PMID- 2904791 TI - [Neurotransmission and the lower urinary tract]. AB - The neurotransmitter activity in the lower urinary tract is very complex. This paper reviews the main substances, known today, their agonists, antagonists, metabolic pathways and their action and discusses the site of action of neuropharmacological substances. The existence of a non-adrenergic, non cholinergic pathway, in parallel with the sympathetic adrenergic and the parasympathetic cholinergic pathways is thus clearly admitted. PMID- 2904792 TI - Selective sparing of NADPH-diaphorase neurons in neonatal hypoxia-ischemia. AB - Excitatory amino acids have been implicated in ischemic neuronal injury. To test this hypothesis in neonatal hypoxia-ischemia, lesions of the cortex and striatum were induced in 7-day-old rats by unilaterally ligating their carotid arteries and subjecting them to hypoxic conditions for 2 hours. Brains examined 1 week later demonstrated, within the regions of ischemic damage, a striking preservation of neurons that stained histochemically for nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) activity. Concentrations of the neuropeptides somatostatin and neuropeptide Y, which colocalize in neurons containing NADPH-d, were unaffected in the areas of ischemic damage. The same pattern of injury with sparing of NADPH-d-reactive neurons was reproduced by focal microinfusion of the excitotoxin quinolinic acid, an endogenous N-methyl-d aspartate (NMDA) agonist, into the striatum. These results support the hypothesis that neonatal hypoxic-ischemic injury is mediated through excitatory transmitters acting at the NMDA receptor and that the NADPH-d-reactive neurons in the neonate are resistant to excitotoxic damage. This pattern of cell vulnerability is unique to the developing striatum and may relate to the distinct pathological appearance of the basal ganglia that follows neonatal asphyxia. PMID- 2904793 TI - Biochemical analysis of caudate nucleus biopsy samples from parkinsonian patients. AB - Biochemical analyses of caudate nucleus biopsy samples from patients with Parkinson's disease undergoing autologous adrenal transplantation were performed. Activity of the dopamine biosynthetic enzyme tyrosine hydroxylase, and concentrations of dopamine and its primary metabolite homovanillic acid were significantly greater than anticipated on the basis of previously published postmortem values. These data suggest that postmortem changes in various biochemical parameters of dopamine function are more rapid than has been generally appreciated. Further analysis of striatal biopsy samples may reveal predictive relationships between striatal indices of dopamine function and therapeutic response to adrenal transplantation. PMID- 2904794 TI - Dementia, parkinsonism, and motor neuron disease: neurochemical and neuropathological correlates. AB - The neurochemical markers for the major neurotransmitter systems were measured in the brain of a patient who died with a dementia-parkinsonism-motor neuron disease (DPMN) syndrome complex. Moderate neuronal loss in the substantia nigra, spongiform changes in the frontal cortex, and moderate anterior horn cell loss throughout the spinal cord were observed. A severe nigrostriatal dopamine deficiency provides the basis for the observed parkinsonian features. The dementia is unexplained. PMID- 2904795 TI - The overshoot effect of intracerebral transplants. PMID- 2904797 TI - Biogenesis of pili adhesins associated with urinary tract infectious Escherichia coli. PMID- 2904796 TI - The pathogenesis and immunology of Vibrio cholerae and Bordetella pertussis. PMID- 2904798 TI - Tissue interactions of Escherichia coli adhesins. PMID- 2904799 TI - Virulence functions and antigen variation in pathogenic Neisseriae. PMID- 2904800 TI - Virulence factors of Bordetella pertussis. AB - Clearly, B. pertussis has evolved very elaborate mechanisms to maintain itself in the human host. Three different proteins (FHA, pertussis toxin and fimbriae) have been implicated in adherence. Furthermore, a number of toxins are produced (pertussis toxin, adenylate cyclase, dermonecrotic toxin, and tracheal cytotoxin) which destroy the clearance mechanisms of the respiratory tract, or suppress the immune response. There is evidence that B. pertussis may survive intracellularly, and the possibility that it is a facultative intracellular parasite should certainly be explored. The availability of a large number of cloned virulence genes, and a system to construct well defined mutants by allelic exchange (Stibbitz et al. 1986) will greatly facilitate the study of Bordetella virulence factors at the molecular level. It opens the possibility to construct avirulent strains, which are still able to colonize and stimulate the local immune response. Such strains may be used as live, oral vaccines, to present (heterologous) antigens to the mucosal immune system of the respiratory tract. PMID- 2904801 TI - Nitrogen inhibition of mycotoxin production by Alternaria alternata. AB - Alternaria alternata produces the polyketides alternariol (AOH) and alternariol monomethyl ether (AME) during the stationary growth phase. Addition of 12 mM NaNO3 to the cultures before initiation of polyketide production reduced the AOH and AME content to 5 to 10% of that of controls. Glutamate and urea also reduced AOH and AME accumulation, whereas increasing the ionic strength did not affect the polyketide content. Adding NaNO3 after polyketide production had started did not inhibit further AOH accumulation, although over 90% of the added NO3- disappeared from the medium within 24 h. Activity of an AME-synthesizing enzyme, alternariol-O-methyltransferase (AOH-MT), appeared in control mycelia during the early stationary growth phase. No AOH-MT activity appeared in mycelia blocked in polyketide synthesis by addition of NaNO3. Later addition of NaNO3 reduced the AOH-MT specific activity to 50% of that of the control, whereas the total of activity per mycelium was the same. The AOH-MT activity in vitro was not affected by 100 mM NaNO3. The results suggest that nitrogen in some way inhibited the formation of active enzymes in the polyketide-synthesizing pathway in A. alternata when it was added before these enzymes were formed. PMID- 2904802 TI - New records of mosquito species (Diptera: Culicidae) in Romania. PMID- 2904803 TI - [Content of endocrine cells of the APUD-system of the lungs in cancer of that organ]. AB - Pulmonary tissue samples were obtained from 17 patients operated on for cancer of the lungs. The samples were subjected to Grimelius argyrophil reaction to detect apud cells. These occurred in clusters and solitary cells in lung tissue adjacent to that involved with cancer. Numerous apud cells were found in 4 out of 12 patients with squamous cell carcinoma and in 1 out of 5 patients with adenocarcinoma. Apud cell hyperplasia occurred more frequently in large tumors with metastases to the lymph nodes of the root of the lung. PMID- 2904804 TI - Systematic gene mapping in man: data management considerations. AB - The application of recombinant DNA technology to linkage analysis is revolutionizing the gene mapping field through the availability of an increasing number of restriction fragment length polymorphisms (RFLP). The successful mapping of the human genome will lead to a new era of research in human genetics with implications for carrier detection and prenatal diagnosis in any number of disorders. In addition, the development of RFLP tightly linked to a disease is critical for the potential identification of the genetic defect. A systematic approach to human gene mapping whereby it is possible to simultaneously screen several disorders for linkage is discussed. Guidelines for the database management, field studies, DNA and lymphoblast cell transformation, family history and laboratory data are included. This methodology represents the integration and application of statistical and molecular genetic, clinical and tissue culture expertise to human gene mapping. PMID- 2904805 TI - Protection of turkey poults from Bordetella avium infection and disease by pili and bacterins. AB - The role of pili in protection against Bordetella avium infection in turkey poults was studied. An isolate that produced the largest number of pili under growth conditions developed in our laboratory was used for preparation of pili and bacterin and for challenge. The pili were isolated, purified, examined by electron microscopy, and tested for purity by gel electrophoresis. Poults were vaccinated with oil-adjuvant pili, formaldehyde- or merthiolate-inactivated bacterins, or a commercial bacterin. Poults were vaccinated once or twice subcutaneously at different ages and challenged intranasally with a pathogenic B. avium isolate 5 days following the last vaccination. A few vaccinated birds had very mild clinical signs. B. avium was isolated from the sinuses of a few vaccinated birds, and growth was scanty. The mean colony counts from tracheal sections was significantly higher (P less than 0.1) in unvaccinated challenged poults than in vaccinated challenged poults. It is postulated that B. avium pili are important immunogens in turkey poults. PMID- 2904806 TI - Diversity of pilus subunits of Escherichia coli isolated from avian species. AB - Pili from 69 avian isolates of Escherichia coli from six diagnostic laboratories in the United States were characterized. Three new pilus types were identified in addition to the three types previously described. A majority of the E. coli isolates (53.6%) examined expressed the classical type 1 pili. PMID- 2904807 TI - Relationship between prostaglandin synthesis and release of acidic amino acid neurotransmitters. AB - The importance of glutamate as an excitatory neurotransmitter in the central nervous system has become increasingly clear. However, the presynaptic mechanism of amino acid neurotransmitter release does not appear to be consistent with existing models. A major source of controversy has been the finding that a significant amount of the amino acid release evoked by membrane depolarization is calcium-independent. It is often implied that this component of release is of cytosolic origin and subserves no neurotransmitter function. In this report, an alternative model is presented which suggests that the depolarization-induced movement of calcium ions into the nerve terminal acts, simultaneously, to stimulate the release of acidic amino acid neurotransmitters from both a vesicular and cytosolic compartment. According to this model, the influx of calcium may indirectly stimulate the biosynthesis of prostaglandins which lower the plasma membrane potential and reverse the electrogenic transport of amino acids to cause a net efflux. Such a mechanism could explain how the vesicular and cytosolic neurotransmitter pools of release are functionally related. PMID- 2904808 TI - Synthesis and nucleophilic reactivity of a series of glutathione analogues, modified at the gamma-glutamyl moiety. AB - A series of GSH analogues with modifications at the gamma-glutamyl moiety was synthesized and purified by following peptide chemistry methodology. Benzyl, benzyloxycarbonyl and t-butyloxycarbonyl protective groups were used to protect individual amino acid functional groups. The formation of peptide bonds was accomplished through coupling of free amino groups with active esters, generated by reaction of the carboxylate functions with dicyclohexylcarbodi-imide and 1 hydroxybenzotriazole. The protecting groups in the tripeptides were removed in a single step by using Na in liquid NH3. Precautions were taken in order to prevent oxidation of the thiol function in the cysteine residue. Thus GSH analogues containing both L- and D-glutamic acid and L- and D-aspartic acid, coupled to cysteinylglycine through both the alpha- and the omega-carboxylate group, were synthesized. Also, decarboxy-GSH and deamino-GSH, lacking one functional group in the glutamate moiety, were prepared. The spontaneous non-enzyme-catalysed nucleophilic reaction of these GSH analogues with the electrophilic model substrate 1-chloro-2,4-dinitrobenzene showed appreciable rate differences, indicating the importance of intramolecular interactions in determining the nucleophilic reactivity of the thiol function in the cysteine residue. In particular, the free amino group in the gamma-L-glutamic acid residue appears to play a crucial role in activating the thiol group in GSH. In an adjacent paper [Adang, Brussee, Meyer, Coles, Ketterer, van der Gen & Mulder (1988) Biochem. J. 255, 721-724] these results are compared with those obtained in a study on the ability of these GSH analogues to act as a co-substrate in the glutathione S transferase-catalysed conjugation reaction with 1-chloro-2,4-dinitrobenzene. PMID- 2904809 TI - Substrate specificity of rat liver glutathione S-transferase isoenzymes for a series of glutathione analogues, modified at the gamma-glutamyl moiety. AB - The substrate specificity of purified rat liver glutathione S-transferases (GSTs) for a series of gamma-glutamyl-modified GSH analogues was investigated. GST isoenzyme 3-3 catalysed the conjugation of 1-chloro-2,4-dinitrobenzene with six out of the nine analogues. alpha-L-Glu-L-Cys-Gly and alpha-D-Glu-L-Cys-Gly showed catalytic efficiencies of 40% and 130% that of GSH respectively. The GSH analogue with an alpha-D-glutamyl moiety appeared to be a highly isoenzyme-3-3-specific co substrate: kcat./Km with GST isoenzyme 4-4 was only about 5% that with GST isoenzyme 3-3, and no enzymic activity was detectable with GST isoenzymes 1-1 and 2-2. GST isoenzyme 4-4 showed some resemblance to GST 3-3: five out of nine co substrate analogues were accepted by this second isoenzyme of the Mu multigene family. Isoenzymes 1-1 and 2-2, of the Alpha multigene family, accepted only two alternative co-substrates, which indicates that their GSH-binding site is much more specific. PMID- 2904810 TI - In situ hybridization patterns of zebrafish homeobox genes homologous to Hox-2.1 and En-2 of mouse. AB - Vertebrate homeobox genes have been identified on the basis of sequence homology to Drosophila segmentation and homeotic genes. We have analyzed the spatial distribution patterns in hatching larvae of transcripts from two different types of zebrafish (Brachydanio rerio) homeobox genes. Tritiated DNA fragments from one zebrafish gene (ZF-21) of the Antennapedia-class and one (ZF-EN) of the engrailed type were used as probes to detect transcripts in larval tissue sections. Both zebrafish genes are expressed mainly in spatially restricted regions of the central nervous system. The transcripts from ZF-21 was detected in the posterior part of the hindbrain, and ZF-EN was found to be most intensively expressed in a restricted domain located in the region of the junction between the mid- and hindbrain. These neural expression patterns are very similar to those of the homologous murine genes Hox-2.1 and En-2 and clearly suggest a strong functional conservation. PMID- 2904811 TI - H2O2 activates CD11b/CD18-dependent cell adhesion. AB - Treatment of monoblastoid U-937 cells with low concentrations of H2O2 caused adhesion of the cells to plastic. The H2O2 induced adhesion was rapid with a t1/2 of congruent to 6 min and was optimally stimulated by 100 microM H2O2 with an ED50 of congruent to 50 microM. The response to H2O2 closely resembled the adhesive response of U-937 cells to phorbol esters in its time dependency, requirement for extracellular Mg2+ and inhibition by cytochalasin B as well as inhibition by monoclonal antibodies against the leucocyte adhesion molecules CD11b and CD18. Phorbol ester treatment of U-937 cells stimulated the phosphorylation of at least three endogenous substrates, pp28, pp34 and pp43, of which pp28 and pp43 also responded to H2O2-treatment with increased 32P incorporation. The results suggest that H2O2 might be a physiological modulator of leucocyte adhesion, possibly operating by activating protein kinase C. PMID- 2904812 TI - Reduction of enzyme activity of tyrosine hydroxylase and aromatic L-aminoacid decarboxylase in clonal pheochromocytoma PC12h cells by carcinogenic heterocyclic amines. AB - Out of carcinogenic heterocyclic amines, which are produced by pyrolysis of tryptophan in food, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 3 amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) were found to reduce the activity of enzymes related to catecholamine metabolism in clonal rat pheochromocytoma PC12h cells. By 6 days' culture in the presence of 10 nM to 10 microM Typ-P-1 and -2, these heterocyclic amines were accumulated in the cells, and activity of tyrosine hydroxylase (TH) and aromatic L-aminoacid decarboxylase (AADC) were reduced markedly. Reduction of these enzyme activity was observed with Trp-P-1 and -2 at the concentrations lower than 1 microM, while cell protein and enzyme activity of a non-specific enzyme, beta-galactosidase were reduced only with 10 microM Trp-P-1. These results show that these heterocyclic amines are neurotoxins specific for dopaminergic neurons. PMID- 2904814 TI - Characterization and regulation by protein kinase C of renal glomerular atrial natriuretic peptide receptor-coupled guanylate cyclase. AB - The nature and regulation of atrial natriuretic peptide (ANP)-sensitive guanylate cyclase in rat renal glomerular membranes was examined. By affinity crosslinking techniques, three bands with apparent molecular masses of 180, 130 and 64 kDa were specifically labeled with [125I]ANP. A specific antibody to the 180 kDa membrane guanylate cyclase of rat adrenocortical carcinoma recognized a 180 kDa band on Western blot analysis of solubilized, GTP-affinity purified glomerular membrane proteins. The same antibody completely inhibited ANP-stimulated guanylate cyclase activity in glomerular membrane fractions. Partially purified protein kinase C inhibited ANP-stimulated guanylate cyclase activity in glomerular membrane fractions. It is concluded that a 180 kDa ANP-sensitive guanylate cyclase is present in glomerular membranes, and that this enzyme is inhibited directly by protein kinase C. PMID- 2904813 TI - Mass measurements of inositol(1,4,5)trisphosphate in rat cerebral cortex slices using a radioreceptor assay: effects of neurotransmitters and depolarization. AB - The specific binding of [3H] and [32P]Ins(1,4,5)P3 to a particulate preparation of bovine adrenal cortex has been used as a radioreceptor assay to determine the concentration of Ins(1,4,5)P3 in agonist- and depolarization-stimulated rat cerebral cortex slices. The resting concentration of Ins(1,4,5)P3 in slices that had been preincubated in a physiological medium was 18.8 +/- 2.6 pmol/mg prot. Carbachol evoked a rapid and dose-related increase in the concentration of Ins(1,4,5)P3. Maximal stimulation (80%) was already seen at the earliest point (10 sec) examined and was maintained for at least 5 min. The EC50 for carbachol was 75 +/- 17 microM and the response was totally suppressed by the muscarinic antagonist atropine. A direct comparison in the same slices was made between mass determinations and [3H]Ins(1,4,5)P3 and [3H]Ins(1,3,4)P3 accumulation determined by h.p.l.c. Although an identical time course was observed for cold and radiolabelled Ins(1,4,5)P3, the greater stimulation of [3H]Ins(1,4,5)P3 may indicate changes in specific radioactivity. Of a variety of other receptor agonists studied, only the glutamate receptor agonist quisqualate, and noradrenaline significantly increased the mass of Ins(1,4,5)P3 in cerebral cortical slices. However, depolarizing concentrations of K+ were as effective as carbachol at elevating this second messenger. PMID- 2904815 TI - 3-Deoxy-D-manno-octulosonate-8-phosphate synthase catalyzes the C-O bond cleavage of phosphoenolpyruvate. AB - The mechanism of 3-deoxy-D-manno-octulosonate-8-phosphate (KDO8P) synthase was investigated. When [18O]-PEP specifically labeled in the enolic oxygen is a substrate for KDO8P synthase, the 18O is recovered in Pi. This indicates that the KDO8P synthase reaction proceeds with C-O bond cleavage of PEP similar to that observed in the 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase catalyzed condensation of PEP and erythrose-4-phosphate (1). No evidence for a covalent enzyme-PEP intermediate could be obtained. No [32P]-Pi exchange into PEP nor scrambling of bridge 18O to non-bridging positions in [18O]-PEP was observed in the presence or absence of arabinose-5-phosphate or its analog ribose-5 phosphate. Bromopyruvate inactivated KDO8P synthase in a time dependent process. It is likely that bromopyruvate reacts with a functional group at the PEP binding site since PEP, but not arabinose-5-phosphate, protects against inactivation. PMID- 2904816 TI - Inhibitory action of tumor-promoting phorbol esters upon beta-adrenergic agonist stimulation of cyclic AMP accumulation in rat prostatic epithelial cells. AB - The pretreatment of rat prostatic epithelial cells with 4 beta-phorbol 12 myristate 13-acetate resulted in an attenuation of beta-adrenergic stimulated cyclic AMP accumulation. The effect was dependent on time and concentration. The maximal extent of isoproterenol stimulation of cyclic AMP production was reduced by 35% after 15-min pretreatment with the phorbol ester at 25 degrees C. Since a similar action was exerted by other protein kinase C stimulators, present results suggest the involvement of this enzyme in a process of desensitization to beta adrenergic agonists of the adenylate cyclase system in rat prostatic epithelium. PMID- 2904817 TI - Effect of styrene and other alkyl benzene derivatives on oxidation of FAD- and NAD-linked substrates in rat liver mitochondria. AB - The effect on energetic metabolism of rat liver mitochondria (RLM) of styrene and other aliphatic benzene derivatives, i.e. toluene, ethylbenzene, alpha methylstyrene and butylbenzene, is studied. It is shown that these compounds uncouple oxidative phosphorylation and this effect is connected with the stimulation of passive entry of protons into mitochondria. The relationship between hydrophobicity of these compounds and their biological activity and mechanism of uncoupling effect are discussed. PMID- 2904818 TI - Effects of pharmacological manipulations on basal and newly synthesized levels of GABA, glutamate, aspartate and glutamine in mouse brain cortex. AB - Concentrations of basal and newly synthesized inhibitory (gamma-aminobutyric acid, GABA) and excitatory (glutamate and aspartate) neurotransmitter amino acids and glutamine were determined in mouse brain cortex. Isotopic enrichment following an intravenous infusion of a stable-labeled precursor, [13C6]D-glucose, was used to estimate the newly synthesized amino acid content. Effects of various pharmacological agents (valproate, aminooxyacetic acid, 3-mercaptopropionic acid, N-methyl-D-aspartate, and 2-amino-7-phosphonohepatanoic acid) were evaluated. The effects of 3-mercaptopropionic acid (an inhibitor of glutamate decarboxylase, a GABA-synthesizing enzyme) were restricted to the GABAergic system. On the other hand, N-methyl-D-aspartate (an agonist of a glutamate receptor subtype) was selective for the glutamate-glutamine system, and its effects were prevented by its selective antagonist, 2-amino-7-phosphonoheptanoic acid. In some cases, divergent effects were observed on basal and new amino acids. This suggested that basal and new amino acids may represent different compartments. The anticonvulsant drug valproate caused an increase in basal but a decrease in newly synthesized GABA. Aminooxyacetic acid caused a dramatic increase in basal GABA without affecting the newly synthesized GABA. This approach may be useful in studying compartmentation and fluxes of neurotransmitters. PMID- 2904819 TI - A 31P-NMR study of the acute effects of altered beta-adrenoceptor stimulation on the bioenergetics of skeletal muscle during contraction. AB - The effects of acute administration of a beta-adrenoceptor agonist (isoprenaline) or antagonist (propranolol) on skeletal muscle contraction and metabolism in the rat have been studied in vivo using 31P-nuclear magnetic resonance spectroscopy and conventional metabolite analysis. In resting muscle, isoprenaline caused a three-fold increase in cyclic AMP concentration, whereas propranolol decreased cyclic AMP concentration by 40%. Isometric contraction of gastrocnemius muscle at a frequency of 4 Hz was caused by supramaximal sciatic nerve stimulation. Altered beta-adrenoceptor stimulation had no effect on contractile performance at any time during the 30 min stimulation period. During the initial stimulation period (0-4 min) intracellular pH decreased to significantly lower values in the isoprenaline-treated animals (6.24 +/- 0.03) compared to either the control (6.44 +/- 0.08) or propranolol-treated (6.42 +/- 0.08) groups. During the subsequent stimulation period (after 15-30 min stimulation at 4 Hz), pH recovered in all experimental groups to values greater than 6.90 and phosphocreatine concentration achieved a constant level at 35-40% of resting values. Calculation of free ADP concentrations using 31P-NMR determined metabolite concentrations and the creatine phosphokinase equilibrium showed that at similar tension development, [ADP]free varied between the three experimental groups; with the lowest (47 +/- 4 microM) and highest (73 +/- 4 microM) values being calculated for the beta adrenoceptor agonist- and antagonist-treated groups respectively. Upon termination of stimulation, recovery of phosphocreatine concentration to pre stimulation values was rapid and similar in all experimental groups. However, gastrocnemius muscle ATP concentration, determined by 31P-NMR and analysis of freeze-clamped muscle, was lower in the isoprenaline-treated group. This study has shown that although altered beta-adrenoceptor stimulation had no effect on contractile performance, significant changes in muscle metabolism were observed in vivo; these effects are discussed with respect to the role of beta adrenoceptors in skeletal muscle. PMID- 2904820 TI - The effect of chronic ethanol feeding on body and plasma composition and rates of skeletal muscle protein turnover in the rat. AB - (1) Sexually immature and mature rats were fed a nutritionally-complete liquid diet or isovolumetric quantities of the same diet in which 36% of the calories as glucose were substituted by isocaloric ethanol. (2) After 6 weeks ethanol feeding, significant reductions in body weight (approx. 15%) occurred in both groups of rats. In immature rats there were significant reductions (7-21%) in bone, gastrocnemius, liver, and skin weights. The total skeletal muscle mass was reduced by 20%. Lung and kidney weights were not significantly altered. In mature rats smaller decreases in organ weights were found, which were only significant for skeletal muscle and skin. The gastrocnemius protein content was significantly reduced in immature but not in mature rats. Plasma protein concentrations were unaltered in both groups. (3) Plasma aspartate aminotransaminase, gamma glutamyl transferase and creatine kinase activities in immature and mature rats were not significantly altered by ethanol feeding, but there were increases in plasma alkaline phosphatase activities in immature, but not in mature, rats. Plasma glucose was slightly raised by ethanol feeding in immature but not mature rats. Plasma triglycerides and insulin were unaltered in both groups of rats. (4) Protein synthesis was measured with a flooding dose of L[4(3)H]-phenylalanine. Rates of protein breakdown were calculated from the difference between synthesis and growth. Fractional and absolute rates of skeletal muscle protein synthesis were reduced by 13-30% by ethanol treatment, in immature and mature rats. Fractional rates of protein breakdown were also reduced by ethanol, by 13 and 19% in immature and mature rats, respectively. PMID- 2904821 TI - Constipation: etiologies and management. PMID- 2904822 TI - Regulation of biotin enzymes. PMID- 2904823 TI - Vasoactive responses of a human cystic artery: adrenoceptor characterization. AB - 1. The pharmacology of various agonists and antagonists was studied in the human isolated cystic artery. 2. The estimated pA2s for the alpha 1-adrenoceptor antagonist prazosin against the alpha-adrenoceptor agonists phenylephrine, alpha methylnoradrenaline and noradrenaline were not significantly different. Similar results were seen for estimated pA2s of the alpha 2-adrenoceptor antagonist yohimbine against these same agonists. Equivalent responses to exogenous noradrenaline and to transmural electrical stimulation were blocked to the same degree by an antagonist with alpha 1-adrenoceptor blocking properties (prazosin). Responses to transmural electrical stimulation, however, tended to be more resistant than equivalent responses to exogenous noradrenaline to blockade by antagonists with alpha 2-adrenoceptor blocking properties (phentolamine, yohimbine). 3. Relaxation to isoprenaline was observed in partially contracted arterial strips using isoprenaline concentrations of up to 10(-6) M, but cumulative addition of higher concentrations of isoprenaline sometimes then evoked a contraction from the relaxation nadir. The relaxation effect of isoprenaline was antagonized by propranolol (10(-5) M). 4. These findings suggest the human cystic artery has almost exclusively alpha 1-adrenoceptors postjunctionally, although prejunctional alpha 2-adrenoceptors may be present; and, it also has some postjunctional beta-adrenoceptors which mediate relaxation. PMID- 2904824 TI - Blocking of histamine-induced conjunctivitis by the oral antihistamine, astemizole. AB - When histamine is applied topically to the eye it produces stinging and inflammation of the caruncle and bulbar and palpebral conjunctiva. This model has been employed in the present study to assess the ability of an oral antihistamine, astemizole, to attenuate the irritation and inflammatory signs. Astemizole 30 mg, taken orally once daily for 1 week, considerably lessened the stinging and significantly lowered the signs of inflammation caused by topically applied histamines. PMID- 2904825 TI - A comparison of bisoprolol and atenolol in the treatment of mild to moderate hypertension. AB - 1. Fourteen patients (mean age 56.0, range 37-61 years; eight females) with mild essential hypertension (DBP greater than 90 mm Hg on placebo) completed a randomised, double-blind placebo controlled crossover study comparing the hypotensive effects of bisoprolol (10-20 mg) and atenolol (50-100 mg) each taken once daily. 2. Bisoprolol had a significantly greater antihypertensive effect than atenolol, reducing sitting blood pressures by 15.9 mm Hg (diastolic) and 21.9 mm Hg (systolic) compared with placebo. Corresponding figures for atenolol were 10.7 and 5.7 mm Hg respectively. Bisoprolol reduced standing blood pressures by 15.9 mm Hg (diastolic) and 22.8 mm Hg (systolic) compared with 7.3 and 8.6 mm Hg respectively for atenolol. 3. Examination of the pharmacokinetic data showed that bisoprolol had a median elimination half-life of 11.2 h during chronic dosing, compared with 6.4 h for atenolol. For bisoprolol, the median clearance fell from 264 ml min-1 after a single dose to 212 ml min-1 during chronic dosing, although clinically significant accumulation would not be expected during chronic administration. 4. Overall, the results suggest that bisoprolol may be a more effective antihypertensive agent than atenolol but larger studies are necessary to confirm these findings. PMID- 2904826 TI - Effect of cicloprolol in intraocular pressure in healthy volunteers. AB - Two oral doses of cicloprolol (50 mg and 100 mg), a beta 1-adrenoceptor partial agonist, were administered to nine healthy volunteers in a double-blind placebo controlled study. Intraocular pressure (IOP) and exercise heart rate were reduced while the resting heart rate and blood pressure remained unchanged. The responses to the two different doses of cicloprolol were similar. PMID- 2904828 TI - [Conditions of activation of guanylate cyclase from human platelets]. AB - Preincubation (50 min, 0 degree C) with nitroprusside increases 12-fold the activity of human platelet guanylate cyclase. The stimulating effect of nitroprusside is enhanced two-fold by dithiothreitol (2 mM) and by 60% by hemoglobin (20 micrograms/ml). Storage of guanylate cyclase preparations (105000 g supernatant) for 2-3 days at 4 degrees C causes a progressive increase of the enzyme activity and diminishes the stimulating effect of nitroprusside. After storage of guanylate cyclase preparations for 3 days, hemoglobin (20 micrograms/ml) augments the stimulating effect of nitroprusside by 130%. It is concluded that the degree of activation of guanylate cyclase by nitroprusside reflects the functional state of the enzyme. PMID- 2904827 TI - Effects of H2-receptor antagonists on ethanol metabolism in Japanese volunteers. AB - The effects of H2-receptor antagonists (cimetidine, ranitidine, and famotidine) on ethanol metabolism were investigated. Neither in aldehyde dehydrogenase (ALDH) 1 deficient subjects nor in those with normal ALDH-1, did the three H2-receptor antagonists and placebo differ in their effects on the pharmacokinetic parameters of ethanol (i.e. peak time (tmax), metabolic rate (k0), peak serum concentration (Cmax), volume of distribution (V) and area under the concentration-time curve (AUC). The AUC of acetaldehyde was slightly but significantly (P less than 0.05) larger only after treatment with cimetidine. Cmax and tmax of acetaldehyde were unchanged. PMID- 2904829 TI - Development and functions of the cytoskeleton during ciliogenesis in metazoa. AB - The different steps of ciliogenesis occurring in quail oviduct were compared to the ciliogenesis pattern described in other metazoan species. Centrioles are generated according to pathways that are found within the same cell: the centriolar and the acentriolar pathways. In the acentriolar pathway, centrioles are generated in the Golgi area, without contact with the preexisting centrioles of the centrosomes, and they migrate toward the apical membrane. The control of this polarized migration was studied by means of several drugs (colchicine, nocodazol, taxol, cytochalasin D, benzodiazepines) and immunocytochemistry. It was suggested that an actin-myosin system was involved in the migration of centrioles, whereas labile microtubules were not necessary. Basal bodies must dock with plasma membrane or cytoplasmic vesicles for the initiation of axonemal microtubule polymerization. This signal is necessary even in the presence of taxol. PMID- 2904830 TI - Leucopenia in rheumatoid arthritis: relationship to gold or sulphasalazine therapy. AB - Leucopenia is one of the most worrying of the many toxic effects of second-line drug therapy for rheumatoid arthritis, and much time and energy is expended in screening for it. Sulphasalazine (SASP) is generally claimed to be safer than some alternative second-line drugs but the reported incidence of leucopenia has varied widely. We have examined, retrospectively, all records of blood counts before, during and after treatment in 326 SASP treated patients and in 213 on gold. Leucopenia on at least one occasion occurred in up to 10% of patients on both drugs but usually recovered spontaneously in spite of continued therapy. 'Serious' leucopenia leading directly to drug withdrawal was a rare event occurring in only one SASP patient and in two patients receiving gold treatment. Most episodes of leucopenia do not require drug withdrawal and may not be drug related. PMID- 2904831 TI - Are slow-acting antirheumatic drugs being given earlier in rheumatoid arthritis? PMID- 2904832 TI - [Use of DNA analysis in the prevention of progressive muscular dystrophies]. PMID- 2904833 TI - [Electron microscopy study of relations between prolongations of dopaminergic amacrine cells and blood vessels in the rat retina]. AB - This immunohistochemical study by electron microscopy has shown the presence of tyrosine hydroxylase immunoreactive processes in more or less close contact with capillaries located in the two plexiform layers of the rat retina. These results, as compared to the literature on the innervation of small blood vessels in the brain, suggest that a dopaminergic innervation is modulating the retinal capillaries' vasomotricity. PMID- 2904834 TI - Human antibody response to outer membrane proteins and fimbriae of Haemophilus influenzae type b. AB - We investigated the prevalence of antibodies in childrens' sera directed against outer membrane proteins (OMP) and fimbriae of Haemophilus influenzae type b. Invasive isolates of H. influenzae type b were enriched for fimbriae production; OMP and fimbriae were resolved by SDS-PAGE. After blotting to nitrocellulose, the proteins were incubated with homologous patient sera or with sera from healthy children. IgG antibodies bound to OMP were detected by immunoperoxidase staining. Immunoblotting was also performed using purified, nondenatured fimbriae as antigen. Nine of the 10 patients studied had antibodies in the acute serum directed against one or more of the OMP. Neither the acute nor the convalescent serum of the remaining patient contained antibodies against OMP. Antibodies against a greater number of OMP were present in the convalescent serum, in comparison to the acute serum, in 4 of the 10 patients. Five of 10 patients had antibodies against the purified fimbriae of an unrelated invasive isolate in either the acute or the convalescent serum. Acute sera from patients more frequently contained antibodies directed against OMP 60K (p less than or equal to 0.01) and OMP 51K (p less than or equal to 0.003) compared with the sera of healthy controls. In contrast, the sera of healthy children more frequently contained antibodies directed against OMP 40K (p less than or equal to 0.04). Sera from both patients and controls contained antibodies against commensal Haemophilus. We conclude that although antibodies against OMP are commonly present in healthy children, antibodies against certain OMP may be markers for susceptibility or protection. PMID- 2904835 TI - Quantitative morphometric comparison between the expression of two different "marker enzymes" in preneoplastic liver lesions induced in rats with low doses of N-nitrosodiethanolamine. AB - Male Sprague-Dawley rats were treated with low doses of N-nitrosodiethanolamine (NDELA) (0.2, 0.63, 1.5, 6 and 25 mg/kg body wt per day). Foci of altered hepatocytes developed at all dose levels. The extent of foci positive for gamma glutamyl transpeptidase (gamma-GT), as demonstrated histochemically in frozen sections, was quantitated morphometrically and compared with the data obtained earlier in the same livers by measuring the extent of foci positive for glucose-6 phosphate dehydrogenase (G6PDH). The area density of foci positive for gamma-GT was much smaller than that of foci positive for G6PDH at all dose levels and time points studied. However, there was an increase in the area density of both gamma GT- and G6PDH-positive foci proportionally to the time of treatment and the total dose of the carcinogen administered. The dose-time relation for the induction of 0.5% gamma-GT positive liver tissue assessed as a double logarithmic plot gives a straight line. The same holds true for the induction of 1% G6PDH-positive liver tissue. The slopes of these straight lines are identical, and they have the same characteristics as the line indicating the time when 50% of the animals developed liver tumors at higher doses. Thus, a close statistical correlation of enzyme altered hepatic foci and the development of hepatocellular tumor exists irrespective of the absolute amount of the area density of the respective foci. PMID- 2904836 TI - Human renal carcinoma: asparagine independence with asparaginase susceptibility in culture. AB - A human renal carcinoma cell line (Caki-1) was examined for asparagine (Asn) dependence and susceptibility to Escherichia coli asparaginase. Because this enzyme hydrolyzes glutamine (Gln) as well as Asn, even though at only 2-3% the rate, Asn- Gln+ and Asn- Gln- media were prepared. Only the former supported Caki growth. The Asn- Gln- medium was then repleted with Asn, Gln, or both. Although Asn repletion failed to promote growth, addition of Gln alone or the combination supported growth as well as complete medium. With [3H]leucine and [3H]mannose incorporation to indicate protein and glycoprotein synthesis, respectively, the Gln repleted medium supported these processes as well as complete medium. Asparaginase added to complete medium was highly toxic to the Caki cells, but this is a reflection of Gln depletion rather than Asn depletion. PMID- 2904837 TI - A gradient of homeodomain protein in developing forelimbs of Xenopus and mouse embryos. AB - The expression of the homeodomain protein XIHbox 1 in developing Xenopus limbs was analyzed using specific antibodies. In the forelimb bud mesoderm XIHbox 1 shows a clear antero-posterior gradient that is strongest in the anterior and proximal region of the forelimb. Hindlimb bud mesoderm is devoid of XIHbox 1, indicating an early molecular difference between arm and leg. The innermost ectodermal cell layer is positive throughout the forelimb and hindlimb bud ectoderm, but no other areas of the skin. Similar results are obtained in developing mouse limbs, suggesting that XIHbox 1 participates in forelimb development in a variety of tetrapods. In early tadpoles analyzed at stages preceding limb bud formation, the lateral plate mesoderm is positive in the region corresponding to the earliest "field" of forelimb information, but not in the hindlimb field. These results suggest a molecular link between morphogenetic fields, gradients, and homeobox genes in vertebrate development. PMID- 2904838 TI - An Ultrabithorax protein binds sequences near its own and the Antennapedia P1 promoters. AB - The homeotic gene Ultrabithorax (Ubx), located in the bithorax complex of Drosophila, encodes a family of closely related proteins that direct the developmental fates of posterior thoracic and anterior abdominal metameres. We have purified a member of the Ubx protein family from an overproducing E. coli strain and have shown that it is sequence-specific DNA binding protein. The protein binds tightly to sequences near its own promoter and near the P1 promoter of Antenna-pedia (Antp), a homeotic gene Ubx is known to repress from genetic studies. The binding sites occur in clusters downstream of the transcription start sites, and far upstream at Antp P1. They range in size from 40 to 90 bp, and contain tandem repeats of the trinucleotide TAA or the related hexanucleotide TAA-TCG. These results suggest that the regulatory activities of Ubx are direct and are mediated by binding of Ubx proteins to promoter region sequences. PMID- 2904839 TI - Gastric fluid volume, pH, and emptying in elective inpatients. Influences of narcotic-atropine premedication, oral fluid, and ranitidine. AB - One hundred and twenty healthy, elective surgical inpatients were randomly assigned to one of four groups. Between two and three hours before the scheduled time of surgery all patients ingested a marker dye, phenol red, 50 mg in 10 ml water, with placebo tablet alone (Groups 1 and 2), placebo tablet with 150 ml oral fluid (Group 3), or oral ranitidine 150 mg with oral fluid 150 ml (Group 4). Patients in Group 1 received oral diazepam or no premedication, while those in Groups 2, 3, and 4 received IM narcotic and atropine one hour preoperatively. Following induction of anaesthesia the residual gastric fluid was aspirated through a Salem sump tube and its volume, pH, and phenol red content measured. Mean volumes were Group 1: 24 ml; Group 2: 13 ml; Group 3: 17 ml; Group 4: 14 ml. Mean pH values were Group 1: 2.99; Group 2: 3.03; Group 3: 3.44; Group 4: 5.28. The amount of phenol red in the samples indicated at least 90 per cent gastric emptying had occurred in 90 per cent of patients. We conclude that, in healthy patients, 150 ml oral fluid is almost completely emptied from the stomach within two hours of ingestion, even when followed one hour later by narcotic-atropine premedication. PMID- 2904840 TI - The onset of ablation of the evoked adductor pollicis muscle twitch in children: a clinical perspective. AB - The time to loss of the adductor pollicis muscle response to ulnar nerve stimulation at 1 Hz (twitch) after succinylcholine, 1.5 mg.kg-1 intravenously (IV), or vecuronium, 0.1 mg.kg-1 (IV), administration was assessed visually in 134 children, age 2-13 yr, during clinically determined, deep halothane, enflurane and isoflurane anaesthesia. The overall time to twitch ablation and duration of succinylcholine's action is in agreement with published times obtained under controlled experimental conditions; the onset time following vecuronium is comparable to those observed during a similar anaesthetic background measured under controlled experimental conditions. Twitch ablation after succinylcholine was achieved in half the time needed following vecuronium regardless of anaesthetic agent. Succinylcholine's and vecuronium's onset time as well as succinylcholine's duration is adequately assessed by the outlined, simple clinical means. The choice of inhalation agent does not affect the time to visible twitch ablation in a clinically relevant manner; nor does it make an appreciable difference, in clinical terms, in succinylcholine's duration of action. PMID- 2904841 TI - Epidural opioids as anaesthesia for extracorporeal shock wave lithotripsy in two patients with cardiac disease. AB - Two patients with cardiac disease underwent Extracorporeal Shock Wave Lithotripsy (ESWL) in the Dornier HM3 machine. In order to minimize cardiovascular changes, epidural opioids (fentanyl 100 micrograms in 10 ml saline was used in one patient and meperidine 50 mg in 10 ml saline in the other patient) were used as an alternative to either general anaesthesia or epidural local anaesthesia. Both patients displayed haemodynamic stability, remained pain-free and experienced no complications. Epidural opioids proved a suitable form of anaesthesia for ESWL in these patients. PMID- 2904842 TI - "Tooth be or not tooth be". PMID- 2904843 TI - The use of antihistamines with a low sedative potential in the treatment of the itching of atopic eczema. PMID- 2904844 TI - [An Italian multicenter study on spasmophilia. Clinical, laboratory and therapeutic evaluation]. PMID- 2904845 TI - [Drug-induced hyperglycemia as a possible cardiovascular risk factor]. PMID- 2904846 TI - [Cardiovascular response to isometric exercise test during beta blocker and diuretic treatment in essential arterial hypertension]. PMID- 2904847 TI - [Problems of psychopharmacological therapy in pregnancy]. PMID- 2904848 TI - [Notes on AIDS]. PMID- 2904849 TI - [New views on the role of ascorbic acid in the central nervous system]. PMID- 2904850 TI - The biochemistry of the mode of action of drugs and the detoxication mechanisms in Trypanosoma cruzi. PMID- 2904851 TI - Cadmium sensitivity differences between liver microsomal drug metabolizing enzyme systems of guinea-pig and rat. AB - 1. Male guinea-pigs (400-500 g) and rats (225-275 g) were given a single dose of cadmium chloride (CdCl2) (2 mg Cd2+/kg i.p.) and 72 hr later the liver microsomal drug metabolizing enzyme activities and Cd levels of tissues and microsomes were determined. 2. No significant differences were noted between Cd treated and control animal tissue weights of microsomal protein contents in either guinea pigs or rats. 3. Cd treatment exhibited significant inhibition of the activities of aniline 4-hydroxylase and ethylmorphine N-demethylase and on the levels of cytochrome P-450 and cytochrome b5 of liver of both species but the degree of inhibition were not the same in the species; they were 23, 34, 16 and 10% in guinea-pigs and 58, 57, 25 and 13% in rats, respectively. 4. No activity changes were observed in liver NADPH-cytochrome c reductase of the species by Cd treatment. 5. The duration of hexobarbital sleeping time was significantly prolonged in both species. However, the prolongation was 1.6 fold in guinea-pigs but 3.4 fold in rats. 6. No significant differences were found between either tissue or microsomal Cd levels of guinea-pigs and rats. PMID- 2904852 TI - The effects of malotilate on hepatic drug metabolizing systems in different strains of rats. AB - 1. In Sprague-Dawley (SD) rats treated for 7 days with malotilate (MAL:250 mg/kg, p.o.), cytochrome P-450 and b5 contents, aminopyrine N-demethylase and heme oxygenase activities were significantly increased. In Wistar rats, cytochrome b5 content and heme oxygenase and delta-aminolevulinic acid synthetase activities were found to be significantly increased. 2. Among the antipyrine metabolites excreted in urine during the 24 hr after antipyrine (100 mg/kg, i.p.) administration, norantipyrine increased significantly in Sprague-Dawley rats, while a significant increase of 4-hydroxyantipyrine was observed in Wistar rats. 3. The serum dimethadione/trimethadione ratio was only found to be significantly increased in Sprague-Dawley rats. 4. These results indicate that malotilate may have inducible effects on hepatic drug metabolizing enzymes, and that it affects the various cytochrome P-450 isozymes from different strains of rat in different ways. PMID- 2904853 TI - Effects of glucocorticoids and catecholamines on maturing rat heart. AB - 1. The negative force-frequency response of normal rat heart was accentuated when the animals were adrenalectomized. Treatment of adrenalectomized animals with dexamethasone restored the normal force-frequency response. 2. Total adrenalectomy increased the sensitivity of rat heart to calcium. 3. Adrenalectomized-dexamethasone-treated hearts were more responsive to epinephrine and ouabain. 4. Total adrenalectomy caused independent myocardial disturbances in calcium handling elements (glucocorticoid effect) and beta receptors (catecholamine effect). PMID- 2904854 TI - Microassay of acetylcholinesterase activity in small portions of single mosquito homogenates. AB - 1. A simple, rapid microassay method is described for measuring acetylcholinesterase (AChE) activity accurately and precisely in small portions of single mosquito homogenates. 2. Up to 30 microassay replicates were possible for individual insects. 3. Microassay data on individual mosquitoes were compared with conventional enzyme assay data acquired using pools of the same homogenates. 4. Under the optimum reaction conditions established, an average Vmax of 7.1 nmol/l/min/mosquito and an average Km of 1.3 x 10(-4) M were observed with acetylthiocholine iodide as substrate. 5. Variability in AChE activity within a sample population of Anopheles albimanus was observed using measurements from individual insects. 6. Such information is fundamental to comparative studies of pesticide physiology (in particular, the resistance phenomenon) in the individual mosquitoes in a population pool; this technique forms the basis for a recently developed resistance microassay. PMID- 2904855 TI - The effect of benzodiazepine on the increase of oxygen consumption in cold exposed rats. AB - 1. Oxygen consumption and rectal temperature of warm and cold acclimated rats were measured after chronic and acute injections of saline or benzodiazepine (diazepam). 2. Benzodiazepine has blocked the increase in oxygen consumption of warm acclimated rats on exposure to cold. 3. After cold acclimation, the benzodiazepine did not affect the increase in oxygen consumption. 4. Benzodiazepine caused a slight hypothermia when injected chronically, but did not affect rectal temperature over a short period of time. PMID- 2904856 TI - Cholinergic binding in the hippocampus of the aging male rat. AB - 1. M1 muscarinic (3H-pirenzepine) and 3H-L-nicotine binding were measured in the hippocampus of male Wistar rats aged 3-4, 10-11 and 24-25 months. 2. The maximal number of M1 binding sites did not differ between age groups. 3. The dissociation constant of M1 binding was higher in old rats than in young rats. 4. The binding of 3H-L-nicotine did not differ between age groups. 5. The number of postsynaptic muscarinic receptors may be preserved, but the conformation of these receptors in the rat hippocampus may be altered during aging. PMID- 2904857 TI - Prediction of the effect of ofloxacine on intestinal absorption: effect of the body weight and substrate concentration. AB - 1. The effect of body weight and initial concentration on the rat small intestinal absorption of DL-8280 (ofloxacine) is studied using a recirculating perfusion technique and an improved HPLC method. 2. A prediction equation is developed under statistical and physiological considerations which correlates both factors with the intestinal absorption rate parameter Kapp. PMID- 2904859 TI - Effects of angiotensin II on isolated toad (Bufo arenarum) aortic rings. AB - 1. The vascular response to Asn1-Val5 angiotensin II (A II) in aortic rings from Bufo arenarum toad was studied. 2. Tachyphylaxis in response to A II could be abolished after incubation with norepinephrine (NE). 3. Phentolamine treatment partially inhibited the pressor effects to A II. 4. Sar1-Ile8 A II and Sar1-Ala8 A II significantly attenuated the vascular effects of A II and did not affect the NE response. 5. We conclude that the pressor response to A II has a direct contractile effect and a catecholamine dependent component in aortic rings of Bufo arenarum toad. PMID- 2904858 TI - Tonic and rhythmic contractions induced by dopamine and related amines in rat vasa deferentia are pharmacologically separable. AB - 1. Exogenous dopamine (DA), octopamine (OA), noradrenaline (NA), and the alpha 1 agonist methoxamine (MX), all induce tonic and rhythmic contractions in the rat vas deferens. 2. Tonic and rhythmic contractions can be separated by use of different concentrations of alpha 1-adrenoceptor antagonists, verapamil, pyrogallol (a COMT-inhibitor) and lowering bath temperature (greater than 20 degrees C). 3. The two types of contraction could not be distinguished by beta adrenoceptor antagonists, cocaine (uptake 1 blocker) or metanephrine (uptake 2 blocker). 4. It is suggested that the tonic and rhythmic contractions induced by amines are mediated by different alpha-adrenoceptors. PMID- 2904860 TI - The prophylactic effect of diphenylhidantoin in the kindling effect on reptiles (Gallotia galloti). AB - 1. Lizards Gallotia galloti received daily 3 mg/kg body wt of diphenylhidantoin (DPH) over a period of 15 days and at the same time the animals were kindled. 2. The progression of the kindling effect was evaluated by counting the number of spontaneous epileptiform potentials, the duration of afterdischarges and the duration of electroencephalographic spontaneous seizures. 3. The diphenylhidantoin treated group, relative to controls presented: (a) significant reduction in the duration of afterdischarges and spontaneous electroencephalographic seizures; and (b) increased frequency of the spontaneous epileptiform potentials. PMID- 2904861 TI - An investigation of the in vitro inhibition of acetylcholinesterase by the carbamate inhibitor eserine sulphate in eserine resistant strains of Drosophila melanogaster. AB - 1. The kinetics of inhibition of AChE by the carbamate inhibitor eserine sulphate were investigated in five resistant strains of Drosophila melanogaster. 2. The dissociation constant (Kd) was higher and the carbamylation constant was lower relative to the control in four of these. 3. No change was observed in the decarbamylation constants (k3) of the five strains. 4. The Vmax of AChE was higher in the five resistant stocks than in the Canton-S/TM2 controls but no change in the Km of AChE for acetylthiocholine was observed. No electrophoretic variants of AChE were detected. 5. No increase in the activity of nonspecific esterases was detected in the resistant lines. 6. These results indicate that resistance to eserine sulphate may occur in D. melanogaster by a reduction in affinity of AChE for the inhibitor. PMID- 2904862 TI - Insecticide-insensitive acetylcholinesterase from a laboratory selected and a field strain of housefly (Musca domestica) (L.). AB - 1. Acetylcholinesterase from the heads of a strain of houseflies selected for resistance to the carbamate insecticide methomyl, and from a methomyl-resistant field strain was found to be less sensitive to inhibition by methomyl than that from a susceptible strain. 2. The enzyme from resistant insects was also more tolerant to malaoxon, dichlorvos and bomyl but not to azamethiphos. 3. The decrease in sensitivity to inhibition appeared to be due to an increase in affinity for substrate. PMID- 2904863 TI - Enhancement of the response of hen granulosa cells to LH with norepinephrine in vitro. AB - 1. The effect of norepinephrine (NE) on progesterone production in hen granulosa cells was examined. After 4 days of the culture, the progesterone production was stimulated by chicken LH but not by NE during a 4 hr incubation. 2. The LH stimulation progesterone production was not affected by the presence of NE when given together with LH, but was significantly increased when the cells were precultured with NE for 2 days. 3. The effect of NE was inhibited by phentolamine, but not by propranolol. 4. The results indicate that NE may enhance the responsiveness of the hen granulosa cell to LH through alpha-adrenergic receptors. PMID- 2904864 TI - Purification and the partial amino acid sequence of an insect neurotoxin from the venom of scorpion Buthus martensi Karsch. AB - 1. A neurotoxic peptide was isolated from the venom of the scorpion Buthus martensi Karsch collected in Henan Province, China. 2. This toxin showed the highest neurotoxic potency to crickets amongst all components in the venom examined. 3. The amino acid composition of the toxin was similar to that of insect toxin 1 of Leiurus quinquestriatus quinquestriatus. 4. The partial primary sequence of the toxin at the N-terminal was very similar to that of an insect toxin of Androctonus australis Hector. 5. We conclude that the neurotoxin we isolated is indeed an insect toxin and thus named it as BmK IT. PMID- 2904865 TI - Effect of cadmium on pulmonary and renal microsomal drug metabolizing enzymes of the guinea-pig. AB - 1. The effect of acute cadmium (Cd) treatment on pulmonary and renal microsomal aniline 4-hydroxylase and ethylmorphine N-demethylase enzyme activities of adult male guinea-pigs were assessed 72 hr following a single dose of Cd ion (2 mg Cd2+/kg i.p.). Tissue and microsomal Cd levels were also determined. 2. There were no significant differences between either lung or kidney tissue weights, microsomal protein contents or enzyme activities of Cd treated and control animals. 3. The tissues and microsomes of Cd-treated animals were found to have significantly higher levels of Cd than those of control animals. In Cd treated animals, tissue and microsomal Cd levels of kidney were found to be higher than that of lung. 4. In vitro addition of cadmium chloride (CdCl2) to incubation mixtures produced concentration related inhibitions of microsomal drug metabolizing enzymes in each tissue. However, in vitro effect of CdCl2 was found to be stronger on drug metabolizing enzymes of kidney than those of lung. In addition, while the strength of Cd effect was more pronounced on the activity of ethylmorphine N-demethylase than that of aniline 4-hydroxylase in the lung, the opposite was observed in the kidney. PMID- 2904866 TI - Cholinergic enzyme activities and muscarinic binding in the cerebral cortex of rats of different age and sex. AB - 1. The choline acetyltransferase and acetylcholinesterase activities in the cerebral cortex and hippocampus and muscarinic binding in the cerebral cortex did not differ significantly between male and female Wistar rats. 2. Choline acetyltransferase activities in the cerebral cortex and hippocampus of rats were not altered during ageing. 3. Acetylcholinesterase activities in these same brain areas were markedly decreased during ageing, possibly reflecting a loss of postsynaptic enzyme activity. 4. When measured using 3H-pirenzepine, binding to the postsynaptic muscarinic receptors was slightly higher in 26-month-old rats than in 12-month-old rats; total muscarinic binding measured using 3H quinuclidinyl benzilate did not alter during ageing. 5. The present study does not support the hypothesis that in the rat brain the number of postsynaptic muscarinic binding sites decreases during ageing. PMID- 2904867 TI - The relaxation induced by indole and nonindole 5-HT agonists in the molluscan smooth muscle. AB - 1. The abilities of two indole agonists and some nonindole agonists to induce relaxation of catch contraction and the influence of the agonists on cyclic AMP (cAMP) levels in the anterior byssus retractor muscle (ABRM) of Mytilus were investigated. 2. 5-MeOT (5-methoxytryptamine) and 5-MeODMT (5-methoxy-N,N dimethyltryptamine) dose-dependently relaxed the contraction. 3. TFMPP (m trifluoromethylphenyl piperazine), PAPP (p-amino-phenyl TFMPP) and mCPP (1-(3 chlorophenyl)piperazine dose-dependently relaxed the contraction, but 2MPP (1-(2 methylphenyl) piperazine and quipazine did not. 4. 5-MeOT (10(-6)M), 5-MeODMT (10(-6)M), TFMPP (10(-4)M), 2MPP (10(-4)M), quipazine (10(-4)M) and 8-OH-DPAT (3 x 10(-5) M) significantly reduced the cAMP levels, but PAPP (3 x 10(-4)M) and mCPP (10(-4)M) did not have any effect on cAMP levels. 5. These findings indicate that the pharmacological properties of 5-HT1-like receptors in the ABRM are similar to those of 5-HT1A receptors in mammalian tissues, and that the changes in cAMP levels induced by the agonists used are unlikely to be directly linked to the relaxation induced by them. PMID- 2904868 TI - The effect of isoprenaline on the phospholipid content of the compact and spongious musculature of the carp ventricular myocardium. AB - 1. After a single injection of 40 mg kg-1 of isoprenaline to the carp, lysophospholipids appear in the tissue of the heart ventricle, ethanolamine plasmalogens increase and choline plasmalogens decrease; phosphatidylinositol is lowered in the spongious layer only. 2. Daily administration of 5 mg kg-1 of the drug leads, after 5 doses, to a dramatic decrease of the diphosphatidylglycerol content; during the subsequent 5 and 10 doses a return to normal values occurs. Shifts in plasmalogens are similar to those found after a single high dose. Some other phospholipids change significantly. 3. All changes reveal that the spongious musculature is more sensitive to the drug than the compact one. PMID- 2904869 TI - Further assessment of a pharmacological effect of Tris buffer. AB - 1. Data are presented confirming that Tris buffer can potentiate teleost melanophore responses to noradrenalin, as recently reported for the first time in Poecilia reticulata (Visconti and Castrucci, 1985). 2. In vitro melanophore responses of Pseudopleuronectes americanus were compared in Tris- and bicarbonate buffered physiological saline solutions. 3. Dose-response curves demonstrate that Tris significantly potentiates melanophore responses to noradrenalin doses between 10(-6) and 10(-5)M in this species. 4. Time-response curves further characterized this effect of Tris on melanophore activity, quantifying the enhancement of the melanosome aggregation rate as well as the dose-related equilibrium levels. PMID- 2904870 TI - Actions of cholecystokinin-related peptides on the gallbladder of bony fishes in vitro. AB - 1. Cholecystokinin (CCK) family peptides elicited dose-related gallbladder contractions in vitro for bluegill (Lepomis macrochirus), killifish (Fundulus heteroclitus), and bowfin (Amia calva). 2. Effects measured by increases in isometric contractions indicated equipotency for nonsulfated forms of CCK and caerulein (CRL; bluegill) and for sulfated CCK and CRL (bluegill, fundulus). Sulfation increased potency. 3. Responses to CCK-related peptides were insensitive to atropine, a muscarinic antagonist, which blocked acetylcholine induced contractions, used for calibration of preparations. 4. Activity of sulfated CCK8 in bowfin, a holostean fish, suggests sensitivity of gallbladder to CCK-related intestinal hormones may be a general feature of osteichthyeans. PMID- 2904871 TI - The pharmacological characteristics of two types of cholinoreceptors in the membrane of dialyzed neurons. AB - 1. The ramped voltage clamp technique was developed as a rapid means of studying the effects of certain nicotinic and muscarinic agents on ionic involvement and conductance changes during acetylcholine (ACh) responses of Helix pomatia neurons. 2. Atropine was found to be a potent cholinolytic on A-type neurons, ACh responses of which are blocked by ouabain and mediated by Na+ and Cl- permeabilities, while d-tubocurarine blocked B-type ACh responses which are insensitive to ouabain and mediated by Na+ and K+ permeabilities. 3. Nicotinic agent butyrylcholine was found to be a potent cholinomimetric on B-type cells. 4. The results suggest that ACh receptors on A-type cells are more "muscarinic" while those on B-type cells are more "nicotinic". 5. It was also suggested that both muscarinic and nicotinic ACh receptors may coexist in the Helix neuronal membrane and the possibility of ACh interacting with one of them is determined by the level of phosphorylation of the membrane proteins. PMID- 2904872 TI - Role of gastrin/pentagastrin in regulation of intestinal cytochrome P-450. AB - 1. In the absence of intraluminal inducers, low "basal" levels of cytochrome P 450 and its dependent MFO activities are detected in the rat intestinal mucosa, and may be regulated by endogenous hormones. 2. Rats were nutritionally maintained by either short term (48 hr) intravenous glucose infusion or chronic (8 days) intravenous hyperalimentation, and were treated with various doses of pentagastrin in the infusate. 3. Regardless of the dose (6-90 micrograms/kg/hr) or duration of infusion (2-8 days), pentagastrin had no effect on small intestinal cytochrome P-450, its dependent MFO activity, or the activity of delta aminolevulinic acid synthetase. 4. The intestinal trophic peptide hormone, gastrin, apparently does not regulate the cytochrome P-450-dependent MFO system of the small intestine. PMID- 2904873 TI - Comparative study of GABA-T from glial cells, neuronal perikarya cells and synaptosomes. AB - 1. This paper presents a fast method of brain cell separation and a comparative study of GABA-T from different cellular compartments (glial cells, neuronal perikarya cells and synaptosomes). 2. The method of cellular separation offers the advantages of rapidity, ease and reproducibility. 3. The GABA-T from the three studied compartments had similar kinetic characteristics in respect of their Kms and Vmaxs. 4. The GABA-T needs PLP to reach its maximum activity; this dependence is related to the enzyme localization. PMID- 2904874 TI - Comparative study on cerebrovascular injuries by three chlorophenoxyacetic acids (2,4-D, 2,4,5-T and MCPA). AB - At toxic doses in rats, 2,4-dichlorophenoxyacetic acid (2,4-D) and 2-methyl-4 chlorophenoxyacetic acid (MCPA) caused injuries in blood vessels in the brain. 2. 2,4-D caused extravasations of the circulating Evans blue-albumin complex also in the spinal cord. 3. By contrast, potency in damaging cerebral vessels was almost non-existent with 2,4,5-trichlorophenoxyacetic acid (2,4,5-T). 4. None of the three chlorophenoxyacetic acids caused such cerebrovascular injuries in mice, guinea pigs, Syrian hamsters, rabbits and chickens. PMID- 2904875 TI - Effects of metal ions on the antioxidant enzyme activities, protein contents and lipid peroxidation of carp tissues. AB - 1. Studies were performed regarding the effects of CuSO4 in concentrations of 5, 10, 25 and 50 ppm and ZnSO4 in concentrations of 10 and 100 ppm on the antioxidant enzyme activities, lipid peroxidation and protein contents of tissues of common carp (Cyprinus carpio morpha L.) exposed to these pollutants for 24 hr. 2. The results demonstrated that CuSO4 was more toxic than ZnSO4 and that both treatments brought about significant changes in these parameters in carp hepatopancreas (liver), gill and white muscle. 3. An increase of the CuSO4 concentration led to significant decreases in the antioxidant enzyme activities, except that of glutathione peroxidase, which was increased significantly, and significant increases in the lipid peroxidation and protein contents. 4. An increase of the ZnSO4 concentration led to slight changes in the antioxidant enzyme activities, lipid peroxidation and protein contents of carp tissues. PMID- 2904876 TI - Diurnal changes in succinate and D-3-hydroxybutyrate dehydrogenase activities of rat liver mitochondria after chronic alcohol consumption and withdrawal. AB - 1. The succinate dehydrogenase (SDH) and D-3-hydroxybutyrate dehydrogenase (HBDH) activities were measured over a 24-hr period in rat liver mitochondria after chronic alcohol ingestion and withdrawal. 2. The diurnal patterns of both the enzyme activities were shown to change after alcohol consumption, with 64-66% decrease in the daily mean levels. 3. The diurnal rhythms of the SDH and HBDH activities are partially restored 24-72 hr after alcohol withdrawal. 4. There was no correlation between changes in both the enzyme activities and the NAD+/NADH ratio of liver mitochondria from control, ethanol-fed and withdrawn rats over the day. PMID- 2904877 TI - Evidence for dopaminergic and opioid involvement in the regulation of locomotor activity in the land crab Gecarcinus lateralis. AB - 1. Computerized analysis of the crabs locomotor behavior revealed an initial increase in activity followed by a gradual decrease over a 12 min observation period. 2. Dopamine, in a dose-dependent manner, inhibits locomotor activity. The effect can be antagonized with the dopamine antagonist, haloperidol. This suggests that dopaminergic influences are involved with locomotor mechanisms. 3. FK 33,824, a stable opioid analog, significantly enhances the initial excitatory locomotor activity. Naloxone, a potent opiate antagonist, can block the excitatory action induced by FK 33 824. This suggests the presence of an opioid modulation mechanism in the regulation of locomotor activity. 4. Concomitant administration of the various agents results in the behavioral characteristics of the agonist appearing when the appropriate antagonist is not present. Thus, administration of dopamine + FK 33,824 + haloperidol results in enhanced locomotor activity. 5. Concomitant dopamine and FK 33,824 administration results in enhanced locomotor activity. This suggests that the opioid mechanism is closer to the last step in affecting the organism's locomotion or in initiating activity. PMID- 2904878 TI - Effects of cooling on alpha-1-adrenoceptor mechanisms in rat aorta. AB - 1. The effects of cooling from 37 degrees C to 25 degrees C on alpha-1 adrenoceptor mechanisms in isolated rat aortic strips were studied. 2. The dissociation constant and the maximum binding for [3H]-prazosin, and the pA2 values (negative logarithm of dissociation constant) of clonidine and prazosin against noradrenaline were not influenced by cooling. 3. These results indicate that cooling did not influence the affinity of a competitive antagonist and receptor concentration. 4. Cooling increased the dissociation constant of noradrenaline but decreased its efficacy. 5. A receptor occupancy-response curve for noradrenaline was a rectangular hyperbola at 37 degrees C but linear at 25 degrees C, suggesting that a relationship between the contractile response and receptor occupancy was changed by cooling. PMID- 2904879 TI - Report of the committee on the genetic constitution of the X chromosome. PMID- 2904880 TI - Report of the committee on human gene mapping by recombinant DNA techniques. PMID- 2904881 TI - Weight gain associated with intensive therapy in the diabetes control and complications trial. The DCCT Research Group. AB - Identifiable risks such as increased frequency of hypoglycemia accompany the treatment of insulin-dependent diabetes mellitus (IDDM) with intensive insulin therapy. During yr 1 of the Diabetes Control and Complications Trial (DCCT), weight gain was identified as a sequela of intensive insulin therapy. The DCCT is a multicenter controlled clinical trial designed to determine the long-term effects of two different diabetes treatment regimens on the early vascular and neurologic complications of IDDM. Subjects randomized to the intensive treatment regimen gained significantly more weight (5.1 +/- 4.6 kg) than the standard treatment subjects (2.4 +/- 3.7 kg, P less than .0001) during the 1st yr of therapy. Higher baseline HbA1c levels and greater decrements in HbA1c during intensive therapy were both associated with greater weight gain. In addition, intensively treated subjects with one or more severe hypoglycemic episodes gained more weight than the intensively treated subjects with no severe episodes. There was no relationship between reported caloric intake or exercise level and the weight changes. These data suggest that improved utilization of calories through a decrease in glycosuria and perhaps other mechanisms led to the weight gain in the intensively treated subjects. The results from the 1st yr of experience in the DCCT indicate that weight gain accompanies efforts to lower blood glucose levels with intensive insulin therapy. Because of the potential adverse consequences of undesirable weight gain, including diminished long-term compliance with therapy and an adverse effect on blood pressure and lipid status, efforts to prevent undesirable weight gain in the intensively treated group of the DCCT are being pursued. PMID- 2904882 TI - Regulation of glycogen metabolism in rat respiratory muscles during exercise. AB - The effect of prolonged exercise on the glycogen level in the respiratory muscles (diaphragm--D, external intercostal--IE and internal--II) has been studied in four groups of rats: 1-control, 2-fasted for 24 h, 3-treated with nicotinic acid and 4-treated with propranolol. There was a sharp reduction in glycogen level in each muscle after 30 min exercise in the control and fasted groups. Exercise till exhaustion further lowered the glycogen level in D in the control group and in IE and II in the fasted group. In the fasted group, the level of glycogen in each muscle, at rest, and after 30 min exercise, and in IE and II muscles after exercise till exhaustion was lower than in the control group. Nicotinic acid did not affect the glycogen level either at rest or during exercise as compared with the control group. Propranolol increased the glycogen level in the muscles at rest and during 30 min exercise. It partially prevented glycogen mobilization in D and IE and fully in II during exercise till exhaustion. In the control group, 24 and 48 h after exercise till exhaustion, the level of glycogen in each muscle exceeded the resting control value. It is concluded that exercise-induced glycogen metabolism in the respiratory muscles differs in some respects from that in the limb or heart muscles. PMID- 2904883 TI - Effect of calcium channel blockade and beta-adrenoceptor blockade on short graded and single-level endurance exercises in normal men. AB - The effect of verapamil (240 mg) on exercise capacity was studied during a short graded and a single-level endurance exercise test in 12 normal volunteers; it was compared to the effects of atenolol (100 mg x day-1). Intake of verapamil, atenolol and placebo, administered according to a randomized, double-blind cross over design, was started 3 days before the exercise tests. Compared to placebo, verapamil did not affect peak oxygen uptake in the graded test or exercise duration in the endurance test. Heart rate, systolic blood pressure, rating of perceived exertion and respiratory data at submaximal and peak exercise were unaffected in either test. On the other hand atenolol reduced maximal oxygen uptake by 5% (p less than 0.001) and endurance exercise duration by 17% (p less than 0.05). Besides marked decreases in heart rate and systolic blood pressure during the two types of exercise, atenolol also reduced oxygen uptake at submaximal exercise levels and it increased the rating of perceived exertion (p less than 0.05), the latter only during the endurance exercise test. PMID- 2904884 TI - Pharmacokinetics of xamoterol after intravenous and oral administration to volunteers. AB - The pharmacokinetics of xamoterol, a beta-adrenoceptor partial agonist under clinical evaluation for the treatment of mild to moderate heart failure, have been studied in 12 healthy male subjects. They received 14 mg i.v. and oral doses of 50 and 200 mg as a tablet and 200 mg as a solution in a 4 way cross-over design. After i.v. dosing the elimination half-life was 7.7 h, the total body clearance was 224 ml.min-1 and the volume of distribution at steady-state (Vss) was 48 l. Sixty-two percent of the dose was recovered unchanged in urine. After oral doses, the absolute bioavailability of xamoterol was shown to be 5% irrespective of whether the dose was administered as a tablet or solution. Peak plasma concentrations occurred at about 2 h for the tablet dose and slightly earlier (1.4 h) for the solution. Peak plasma concentration, AUC and urinary recovery of unchanged drug increased in proportion to dose. The apparent elimination half-life after oral doses (16 h) was significantly longer than that observed after an intravenous dose. Despite the low bioavailability, the degree of inter-subject variability of oral bioavailability was small probably indicating that the controlling factor is the hydrophilic nature of the molecule rather than extensive first pass metabolism or poor dissolution of xamoterol from the tablet formulation. PMID- 2904885 TI - In vitro T cell responses to a candidate Epstein-Barr virus vaccine: human CD4+ T cell clones specific for the major envelope glycoprotein gp340. AB - Specific T cell proliferation was observed in short-term blood mononuclear cell cultures set up from Epstein-Barr virus (EBV)-immune individuals and challenged either with UV-irradiated EB virions or with a candidate subunit vaccine preparation, the purified envelope glycoprotein gp340 incorporated into immune stimulating complexes (gp340 iscoms). Limiting dilution culture of the activated T lymphoblasts in interleukin 2-containing medium generated stable CD3+CD4+CD8- T cell clones. Particular clones showing virus-specific proliferation in preliminary screening assays were selected for more detailed study. Three gp340 iscoms-induced clones from EBV-immune donor CG responded specifically to restimulation either with UV-EBV or with purified gp340 iscoms in the presence of autologous antigen-presenting cells (APC). Both T cell-depleted blood mononuclear cells and the EBV-transformed B cell line (treated with Acyclovir to block endogenous gp340 production) could be used for presentation, the latter being the more efficient when gp340 iscoms was the source of antigen. Blocking studies with monoclonal antibodies to HLA class II antigens and experiments using HLA-typed allogeneic APC indicated that all three gp340-specific CG clones were restricted through the HLA-DR2 antigen. One gp340 iscoms-induced clone from another EBV immune donor, MR, likewise showed gp340-specific proliferation, in this case restricted through a HLA-DR4 antigen. Using HLA-DR-homozygous B cell lines representing the five known DR4 subtypes, efficient presentation of gp340 to this T cell clone was observed with both DR4 Dw4 and DR4 Dw14 antigens. Parallel experiments on one UV-EBV-induced T cell clone from donor MR gave a different pattern of results; these cells appeared to be specific for a virus structural component other than gp340 and to be restricted through an HLA-DP determinant. PMID- 2904887 TI - [Synthesis and antiparasitic activity of arylproprenones in the nitro-5-imidazole series]. AB - The synthesis of new arylpropenones derived from 1-methyl-5-nitro imidazole is described. The investigation of some antiprotozoal properties has shown that compounds with the groups 4-hydroxyphenyl, 4-chlorophenyl or thiophenyl have trichomonacidal activity similar to that of metronidazole. PMID- 2904886 TI - Concomitant infection of HTLV-I and HIV-1: prevalence of IgG and IgM antibodies in Washington, D.C. area. AB - Serum samples collected from four groups of individuals in the Washington, D.C. area were examined for the presence of IgG and IgM classes of antibody reacting against HTLV-I and HIV-1. These four groups were: (1) healthy adults with negative premarital VDRL test for syphilis (n = 113), (2) miscellaneous common disease patients (n = 155), (3) drug abusers (n = 130), and (4) homosexual men (n = 187). The former two groups are considered to be low-risk groups, and the latter two, high-risk groups. The prevalence of IgG antibody on ELISA/Western blot tests for these groups were respectively: (1) 5.3%/1.8%, (2) 5.2%/1.9%, (3) 13.9%/4.6%, and (4) 4.3%/1.6% for HTLV-I, and (1) 2.7%/0.9%, (2) 4.5%/0%, (3) 12.3%/5.4%, and (4) 8.0%/5.9% for HIV-1. Instances of possible concomitant infection as shown by the presence of antibodies against both HTLV-I and HIV-1 were found only in the latter two high-risk groups, i.e. two (1.5%) in group (3), and three (1.6%) in group (4) as confirmed by both Western blot and immunofluorescence tests. Out of 97 sera collected from drug abusers in 1985-86 which had IgG antibody by Western blot test against HIV-1, 23 (23.7%) were HTLV-I antibody positive by ELISA test (Group 5), and 8 of these were confirmed by Western blot test. Among these 8 persons, IgM antibody against HTLV-I was found in 2, while that against HIV-1 was positive in 7 persons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2904888 TI - 1H-NMR studies on nucleotide binding to the catalytic sites of bovine mitochondrial F1-ATPase. AB - The conformation of adenine nucleotides bound to bovine mitochondrial F1-ATPase was investigated using transfer nuclear Overhauser enhancement measurements. It is shown that all nucleotides investigated adopt a predominantly anti conformation when bound to the catalytic sites. Furthermore, the experiment suggests that 8-azido-ADP and 8-azido-ATP, which are predominantly in the syn conformation in solution, are in the anti conformation when bound to F1 catalytic sites. PMID- 2904889 TI - Somatostatin activates glibenclamide-sensitive and ATP-regulated K+ channels in insulinoma cells via a G-protein. AB - Somatostatin, an hyperglycemia-inducing hormone, was studied in rat insulinoma (RINm5F) cells using 86Rb+ efflux techniques. 86Rb+ efflux is stimulated by somatostatin in a dose-dependent manner. The half-maximum value of activation is 0.7 nM. Somatostatin-induced 86Rb+ efflux is abolished by the hypoglycemia inducing sulfonylurea, glibenclamide, a known blocker of ATP-regulated K+ channels. Somatostatin activation is prevented by pretreatment of insulinoma cells with pertussis toxin. 86Rb+ efflux studies show that somatostatin activates an ATP-dependent K+ channel. PMID- 2904890 TI - Bone density and reproductive hormones in patients with neuroleptic-induced hyperprolactinemia. AB - To study the prevalence of osteoporosis and hyperandrogenism in neuroleptic induced hyperprolactinemia, the authors evaluated 10 patients. Three were amenorrheic, while seven had oligomenorrhea. Nine patients had galactorrhea. The Ferriman-Gallway hirsutism score was 12 +/- 2. Vaginal smear maturation value was 53 +/- 8. Bone density, measured by dual photon absorptionometry in the spine, femoral neck, Ward's triangle, and trochanteric region, was 98 +/- 1.5, 92.7 +/- 3, 88.5 +/- 4.2, and 92.6 +/- 3.3 percentile of controls matched for age, sex, weight, and ethnicity, respectively. Serum prolactin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone sulfate (DHEAS), total testosterone, and free testosterone were 82 +/- 10 ng/ml, 8.5 +/- 1.1 mIU/ml, 11.1 +/- 2.6 mIU/ml, 4695 +/- 594 ng/ml, 90 +/- 17 ng%, and 2.36% +/- 0.3%, respectively. Serum thyroid-stimulating hormone (TSH) and free thyroxine index were normal. Bone density strongly correlated with vaginal maturation value (r = 0.904, P less than 0.01). It is concluded that (1) neuroleptic-induced hyperprolactinemia is associated with hirsutism and androgen excess primarily of adrenal origin and (2) a subset of these patients is at an increased risk of developing osteoporosis. It may be possible to identify patients at risk of osteoporosis by examining vaginal smears for maturation value. Early detection and management are imperative in this group of patients. PMID- 2904891 TI - [Effect os alpha-adrenoblockaders on the system of hemostasis]. PMID- 2904892 TI - Pelvic assessment and cephalo-pelvic disproportion in Central Tanzania. AB - Among 201 primigravidae, pelvic assessment was analyzed prospectively during the third trimester to detect patients likely to suffer from cephalo-pelvic disproportion (CPD). If the sacral promontory (SP) was reached by the index finger (9.0-9.5 cm true conjugate) the pelvis was regarded as "suspect". All patients who later developed CPD were in this group. Of the screened primigravidas, 22% were advised to deliver in the hospital. Pelvic assessment is an important screening tool during antenatal care to detect high-risk primigravidas. PMID- 2904893 TI - The relationship of increased amniotic fluid volume to perinatal outcome. AB - We studied a group of 135 patients with polyhydramnios diagnosed on the basis of ultrasonic findings (greatest vertical diameter of the liquor column greater than or equal to 8.0 cm) between 32 and 36 weeks gestation (study group). We compared the obstetric characteristics and perinatal outcome of the study group with a similar number who constituted our control group. The incidence of women aged 20 years or less was higher in the study group (8.9%) compared with 4.5% in the control group. Of the 135 patients who were diagnosed to have polyhydramnios ultrasonically, the clinical diagnoses prior to referral for ultrasonic scanning, were, suspected large for date fetuses in 34 patients (25.2%), clinically suspected polyhydramnios in 28 (20.7%), gestational diabetes in 21 (15.6%) and insulin dependent diabetes in 6 (4.4%) compared with 13.3%, 5.2%, 3.0% and 0.7%, respectively in the control group (P less than 0.05). Preterm delivery occurred in 11.1% in the study group compared with the incidence of 6.7% in the control group. The incidence of fetal distress, low Apgar Score, macrosomic infants, major fetal anomalies, gross and corrected perinatal mortality rate and admission to special/intensive care nursery was significantly higher in the study group compared with that of the control (P less than 0.01). We found ultrasonic examination is a reliable technique to assess the amount of amniotic fluid volume and it alerts the clinician to possible future problems in pregnancy, labor and neonatal period. PMID- 2904894 TI - Eclampsia and placental abruption: basic patterns, management and morbidity. AB - The clinical analysis of 46 cases of abruptio placentae complicating eclampsia showed that, (1) the severity of the eclamptic symptoms influenced the extension of the placental separation, (2) older and multiparous women had more complications, larger placental separations and higher mortality, (3) there were ten maternal deaths due to the additive effects of various complications, (4) total perinatal mortality was 44.7% and it was 40.5% for fetuses above 1000 g, (5) optimum timing of delivery by cesarean operation offered slightly better prognosis, even in cases with antepartum fetal death, (6) the dominant factor for morbidity was the stage reached by the combined pathology before receiving qualified medical care, and (7) the wide variability of these cases suggested that the basis for the complete management should be a series of sound and individually tailored decisions to be carried out in a reasonably short time. PMID- 2904895 TI - The incidence, sociobiological factors and obstetric complications associated with large infants at Ilorin, Nigeria. AB - The study examined the incidence, sociobiological factors and obstetric complications related to the deliveries of 351 large infants, weighing 4000 g and above, and compared them to the findings among controls, comprising of 6563 full size term infants; all deliveries took place at the University of Ilorin Teaching Hospital, June-December, 1983. Large infants constituted 4.7% of singleton deliveries and the male/female ratio among large infants was significantly higher than among controls. Significant associations were found in the occurrence of large infants with increasing age, parity and weight, but not with height. Large infants occurred more frequently among the high social class women who could pay for health services. Rate of cesarean section and postpartum hemorrhage increased four-fold with deliveries of large infants. Shoulder dystocia complicated six deliveries resulting in four stillbirths and two cases of Erb's palsy. It is advocated that prenatal screening for gestational diabetes be performed on mothers with advanced maternal age, high parity, overweight and particularly of high social class. PMID- 2904896 TI - Comparative study of single layer and conventional closure of uterine incision in cesarean section. AB - Single layer interrupted suture closure of uterine wound incisions represent a viable choice over conventional closure since the operation not only has benefits in case of performance but also possesses a rational basis for the avoidance of ischemia of the wound, infection and hematoma formation. There is a distinct advantage of single interrupted suture closure over conventional closure because there is a substantially higher number of normal hysterograms in this group showing good integrity of the scar in the uterus. PMID- 2904897 TI - The kick chart in high-risk pregnancies: a two-year experience in Zimbabwe. AB - A kick chart has been recorded by 200 high-risk pregnancies during their antepartum hospitalization. Except for 19 mothers who presented with an unreliable count, this study suggests a good correlation between an abnormal kick chart and an increased risk of intrauterine death. The obstetrical outcome was much better among the patients with a normal kick chart compared to those with an abnormal count. This easy, cheap, low-technology test could be useful in developing countries when monitoring of fetal well-being is required. PMID- 2904898 TI - Complications associated with genital colonization in pregnancies with and without cerclage. AB - Cultures from the cervical milieu were taken from 24 antibiotic-treated patients (group A) and from 25 patients with no antibiotic treatment (group B). Both groups had undergone cerclage and were compared to 30 randomly chosen pregnant patients without cerclage (group C). Positive cultures were obtained in 70.8% and 48% before cerclage and in 66.7% and 68% after cerclage in groups A and B, respectively. These were not significantly different from group C (56.7%). Escherichia coli was found in over 75% of positive cultures. The rate of premature deliveries and premature rupture of the membranes were significantly higher in the cerclage groups. Maternal morbidity was significantly higher in group A compared to B and C. Our data suggest that bacterial colonization of the cervix and the vagina is not influenced by cerclage and antibiotics. It is concluded that cervical cerclage is associated with increased morbidity, therefore it is indicated only for definite anatomic and/or functional defects. PMID- 2904899 TI - Maternal mortality in Anambra State of Nigeria. AB - The maternal mortality rate (MMR) in 10 hospitals scattered all over Anambra State in a 5-year period was studied. The hospitals covered urban, semi-urban and rural areas. The MMR varied from 1.8 to 13 per thousand with a mean of 4.97 per thousand. The causes of and various factors influencing this high mortality rate are examined as well as the avoidable factors. Suggestions are made for its reduction based on accurate data collection, improved health facilities, improved socio-economic status and basic education. PMID- 2904900 TI - Ectopic pregnancy: analysis of 100 cases. AB - This study of 100 consecutive ectopic pregnancies in Zulu patients emphasises the role of less sophisticated diagnostic methods such as colpopuncture when beta human chorionic gonadotrophin (beta HCG) assay is not available. Infertility (61%) and previous pelvic infection (32%) were associated factors. The ectopic gestation was ruptured in 93% of cases. PMID- 2904901 TI - Serologic diagnosis of Chlamydia trachomatis infections. AB - The serology of various infections often caused by Chlamydia trachomatis including complications such as pelvic inflammatory disease (PID) and infertility was investigated comprehensively among diverse patient groups in a developing country using initially an indirect immunofluorescent antibody test (IFA). Any positives detected were further examined by a micro-immunofluorescence (MIF) method for the presence of type specific anti-chlamydial IgG/IgM antibodies. Conventional cell culture was carried out concurrently to compare culture results with serologic results. Among 416 patients (107 males and 309 females) C. trachomatis D-K antibodies to IgG were identified in 87 (20.9%) and to type specific IgM were identified in 11(2.6%) patients. Cell culture identified C. trachomatis in 60 patients (14.4%). C. trachomatis IgG antibodies were detectable in 6.4% of chlamydia culture negative patients. PMID- 2904903 TI - Histopathology of tubal pregnancy. AB - The histopathological examination of several sections of tubal ectopic pregnancies shows that the growth of the trophoblast usually takes place in an extraluminal subperitoneal site and dilation of the tube is caused by coagulated blood and not by the trophoblast. For conservative surgery of the tube it is necessary to keep in mind the histopathological findings of tubal pregnancies. PMID- 2904902 TI - The incidence of urogenital Chlamydia trachomatis infections among patients in Kumasi, Ghana. AB - The incidence of urogenital chlamydia infections among selected patients in Kumasi, Ghana was evaluated using an immunofluorescent monoclonal antibody technique. Chlamydia trachomatis was identified in 4 of 110 patients presenting for prenatal care, 2 of 55 female patients with infertility and 6 of 15 males with acute urethritis. The findings demonstrate that C. trachomatis is a frequently identified pathogen among male patients presenting with symptoms of acute urethritis; however, the incidence of chlamydia infections among asymptomatic patients is relatively low. PMID- 2904904 TI - Cervical encerclage--a stitch in time: analysis of 23 cases. AB - Cervical incompetency has been recognized as a cause of repeated reproductive loss. Currently many surgeons cast doubt on the existence of cervical insufficiency and the efficiency of encerclage to salvage the situation. Over a period of 3 years we did cervical encerclage for 23 patients with recurrent pregnancy loss in whom all other causes were ruled out. Twenty-one patients benefitted by the procedure, only one ended in missed abortion and one patient had preterm delivery with early neonatal loss. We had a fetal salvage of 91.3%. Birth weights of the babies were above 2500 g in 65.2%. In our experience, with proper selection, patients benefitted from encerclage performed at the appropriate time. PMID- 2904905 TI - Differential rates of carcinoma of cervix uteri among the Chagga and Pares of Kilimanjaro region, Tanzania. AB - Cervical cancer is the commonest cancer among females in Northern Tanzania. Female Pares showed a higher age specific incidence rate especially in the older age groups (50-65 years) compared to Chagga females. The incidence per year per 100,000 women, corrected to the standard African population was 5.0 in Moshi and 9.6 in Pare, during the study period. Both of these ethnic groups live in a limited geographic region and are culturally similar. The higher rate of cervical cancer among the Pares seems to be due to their increased sexual activity which is usually with several male partners. PMID- 2904906 TI - Serum lipids and lipoproteins in women with polycystic ovarian disease with different body mass index. AB - A study to determine serum lipids and lipoproteins in 54 women with polycystic ovarian disease (PCOD) who had varying body mass index (BMI) compared to the normal regular menstruating women was carried out. All patients had similar hormonal profiles of PCOD and differed from the control group. The significant observations were high level of triglyceride and low percentage of alpha lipoprotein in obese PCOD. The BMI was positively correlated with serum triglyceride level, beta and prebeta lipoproteins but inversely correlated with high density lipoprotein (HDL) cholesterol, the low density lipoprotein (LDL) cholesterol/HDL cholesterol ratio and alpha lipoprotein. No significant correlation between lipids, lipoproteins and testosterone levels was observed. It appeared that the alteration of serum lipids and lipoproteins in PCOD is due to the effect of obesity. PMID- 2904907 TI - Sonographic study of the endometrial responses to ovarian hormones in patients receiving ovarian stimulation. AB - A total of 486 endometrial sonograms from 60 cases were reviewed to study the endometrial responses. There was a significant change in the proportion of each sonographic criterion between the pre- and post-ovulatory phases. After ovulation endometrial image showed distinct changes, and its thickness increased. These results suggest that classification of endometrial sonograms according to criteria and thickness measurements provides useful information. PMID- 2904908 TI - Family planning practice among Nigerian student midwives. AB - An analysis of the various contraceptive methods practiced by a total of 462 student midwives from the Northern and Southern parts of Nigeria over a 3-years period is presented. The differences in age distribution, the type of contraceptive agents used, the reasons for using them, and the side effects in the two groups are statistically significant. The need to provide acceptable contraceptive advice to the rural communities by the midwives is discussed. PMID- 2904909 TI - Serum methotrexate and human chorionic gonadotropin concentrations during five day chemotherapy for low-risk metastatic gestational trophoblastic neoplasia. AB - A recent report of serum methotrexate (MTX) levels measured during treatment of gestational trophoblastic neoplasia (GTN) led us to determine MTX and human chorionic gonadotropin (beta-hCG) levels in a patient with low-risk metastatic GTN with a pulmonary metastasis. Peak MTX concentrations exceeded 10(-6) mol/l considered by many investigators to be within the therapeutic range against many human tumors. Serum beta-hCG levels did not decline during MTX administration; however, after 5 days of MTX a steep dose-response curve was observed which continued during 5 courses of chemotherapy. PMID- 2904910 TI - Primary hepatic pregnancy. AB - Abdominal pregnancies are a small fraction of ectopic pregnancies. They usually implant on the peritoneal surface after partial disruption of the initial implantation site in the tubes. The pelvic cavity is the preferential site, but they have been reported from all over the peritoneal cavity. In the present case the pregnancy was situated on the surface of the right liver lobe. Abdominal pregnancies usually present with acute hemoperitoneum and the pre-operative diagnosis is extremely difficult. The possible role of IUDs as an etiological factor is briefly discussed. PMID- 2904911 TI - Unexpected dystocia secondary to a fetal sacrococcygeal teratoma: a successful outcome. AB - Sacrococcygeal teratoma is a rare cause of dystocia. With recent advances in perinatal care, particularly the increasing use of maternal ultrasound, it is unlikely that unexpected dystocia secondary to this tumor will be seen by many physicians. Recent reports of this type of dystocia are rare and infant mortality secondary to it is high. However, if and when encountered, such dystocia need not imply a bad prognosis for either mother or infant. This is a report of successful management of one case as well as a presentation of recently reported cases and recommendations for management. PMID- 2904912 TI - Massive ascites associated with endometriosis in a Nigerian African. AB - A case of endometriosis with massive ascites in a 19-year-old Nigerian African is reported. This is an unusual combination and it is likely that most gynecologists and general physicians would never see such a case. The presentation and management of this entity is discussed. PMID- 2904913 TI - Virilization due to a rare ovarian tumor in a postmenopausal woman. AB - A 60-year-old postmenopausal woman presented with evidence of hirsutism, alopecia and mild virilization. Clinical examination and biochemical abnormalities suggested that the source of androgen excess was ovarian, and an ovarian tumor was confirmed and removed at laparotomy followed by normal endocrine profile in the postoperative period. PMID- 2904914 TI - Endoscopic suspension of vaginal prolapse. AB - A new alternative for the surgical treatment of vaginal prolapse is presented in which the prolapse vagina is brought towards the abdominal wall using an extraperitoneal abdomino perineal approach with endoscopic control. The technique consists of a small suprapubic transverse incision to expose the abdominis rectus muscle aponeurosis. A Stamey needle is passed retropubically to the vagina and the extremity of a helicoidal suture previously made in the vaginal wall is introduced in the eye of the needle. It is then withdrawn to bring the thread to the suprapubic region. The maneuver is repeated on the other side and the threads are tied up over the aponeurosis of the rectus abdominis muscles, bringing the vagina to its original position. Endoscopic control is important to avoid bladder perforation. PMID- 2904915 TI - Brenner tumor as encountered in a southern Nigerian Hospital. AB - Brenner tumor is an uncommon ovarian tumor whose etiology and hormonal activity have aroused controversies. The salient features of three cases of this tumor seen at the University of Port Harcourt Teaching Hospital, Nigeria, between March 1981 and March 1987 are discussed. In one case, the tumor was bilateral and was associated with secondary polycythemia. Another case was associated with a full term pregnancy and here the tumor contained luteinized stromal cells. Although such cells are usually associated with estrogenic activity, the full term pregnancy in this case will suggest at best a low level of hormonal activity. The last case was an incidental microscopic lesion in a postmenopausal woman. PMID- 2904916 TI - Serum lactic dehydrogenase and its isoenzymes in patients with ovarian dysgerminoma. AB - Lactic dehydrogenase (LDH) is a glycolytic enzyme that may be elevated in the serum of patients with gonadal and extragonadal germinomas. In this report, a case of unilateral ovarian pure dysgerminoma with remarkably elevated levels of serum LDH is presented. After complete excision of the tumor, serum LDH levels promptly returned to normal levels. Although an electrophoretic pattern of serum LDH isoenzymes was within normal limits pre-operatively, an increase in LDH-1 and 2 was found 1 week after operation. Seventeen additional examples of ovarian dysgerminomas with elevated serum LDH levels have been reported in the English literature including five cases who had high levels of two fast fractions of LDH. These data suggest that serum LDH levels and its isoenzymes pattern are useful tumor markers for diagnosis and post-therapy surveillance in patients with ovarian dysgerminomas. PMID- 2904917 TI - Pelveo-peritoneal schistosomiasis as a cause of primary infertility. AB - An unusual case of bilharziosis apparently leading to anatomic infertility in a Kuwaiti woman is reported. PMID- 2904918 TI - Antipsychotic withdrawal phenomena in the medical-surgical setting. AB - The literature describing nondyskinetic antipsychotic withdrawal symptoms is reviewed. The withdrawal of antipsychotic agents can result in nausea, emesis, anorexia, diarrhea, rhinorrhea, diaphoresis, myalgias, paresthesias, anxiety, agitation, restlessness, and insomnia. Psychotic relapse is often presaged by increased anxiety, agitation, restlessness, and insomnia. However, the temporal relationship of these prodromal symptoms to reduction in the dosage or discontinuation of neuroleptics distinguishes them from the effects of abrupt withdrawal. PMID- 2904919 TI - [Hygienic problems of using computers in the learning process in secondary schools]. PMID- 2904921 TI - [Alzheimer dementia: new knowledge and the road to therapy. International workshop. Konstanz, 27 April-1 May 1988. Abstracts]. PMID- 2904920 TI - Energy efficiency of different mechanistic models for potassium ion uptake in lower eukaryotic cells. AB - Different mechanistic models for potassium ion uptake are analyzed by an equilibrium-thermodynamic formalism in terms of their comparative efficiency in setting chemical potential differences of the potassium ion of different magnitudes across the plasma membrane of lower eukaryotic cells. The possible adaptive advantages for a multimode mechanism(s) operating in alternative modes depending on the physiological and/or environmental conditions of the cells are discussed. PMID- 2904922 TI - [Reinduction of GGT-positive foci in the hamster cheek pouch by a resumption of DMBA application]. PMID- 2904923 TI - Narcotic usage in renal failure. PMID- 2904924 TI - Leachability of a new plasticizer tri-(2-ethylhexyl)-trimellitate from haemodialysis tubing. AB - In two groups of patients on chronic haemodialysis treatment, the common PVC-DEHP blood tubing was replaced with tubing containing tri-(2-ethylhexyl)-trimellate (TOTM) as plasticizer. The aim of the present study was to measure the amount of TOTM and/or its metabolites (TAE s) in plasma, resulting from TOTM that might leach from the dialysis tubes. The arterial levels of TAE s at the start of the dialysis sessions were monitored by Selected Ion Monitoring (SIM) analysis once a week for a period of 42 days. A gradual decrease in TAE was observed during the first 21 days of the haemodialysis treatment with the PVC-TOTM tubes. After three weeks, the TAE levels remained constant until the end of the study. On day 120 of the haemodialysis treatment, the plasma TAE concentrations from the inflow and outflow tubes of the dialyzer were monitored during a single haemodialysis session at different times after starting dialysis. At the beginning of the dialysis session, the mean concentration of TAE was 55.81 +/- 14.98 ng/ml (mean +/- standard error), while at the end the levels were 73.34 +/- 17.05 ng/ml. There were no significant differences between venous and arterial sampling points in the trimellitic ester concentrations. Less TOTM is apparently leached from haemodialysis than DEHP. TOTM can be recommended as an alternative plasticizer to DEHP, but its possible toxicity in humans should be investigated before it can be used routinely. PMID- 2904925 TI - Renal tolerance of fleroxacin in healthy volunteers. AB - In order to evaluate kidney tolerance of fleroxacin, a new fluoroquinolone, we performed a volunteer study with 16 healthy males, 20-27 years old. On three consecutive days 800 mg of fleroxacin was administered orally. Alanine aminopeptidase and distal- and pan-tubular antigens were determined in 24 h urine collections with specific monoclonal antibodies. Routine haematological and biochemical parameters were determined daily and were in the normal range during the follow-up. No significant changes in excretion of alanine-aminopeptidase and of the urinary antigens were observed during the three days of fleroxacin administration and on the following three days. The results obtained in this volunteer study indicate that fleroxacin has no nephrotoxic side effects. PMID- 2904926 TI - Current status of internal mammary artery as a conduit for myocardial revascularisation. PMID- 2904927 TI - Fibrous papule: a tumor of fibrohistiocytic cells that contain factor XIIIa. AB - Factor XIIIa, a blood coagulation factor, has been found in a variety of cell types, including dendritic reticulum cells and fibroblast-like mesenchymal cells. We hypothesized that fibrous papule, a lesion of uncertain histogenesis, was composed of dermal stellate cells and in this report demonstrate that this neoplasm consists of cells that contain this factor. Nevus cells do not contain factor XIIIa. PMID- 2904928 TI - Treatment of nonphobic anxiety disorders: a comparison of nondirective, cognitive, and coping desensitization therapy. PMID- 2904929 TI - Lymphocyte subclasses and depression. PMID- 2904930 TI - Lack of subsensitivity to terfenadine during long-term terfenadine treatment. AB - Eleven healthy male volunteers ingested terfenadine, 60 mg, every 12 hours for 56 days. Compliance was monitored strictly throughout the study. Before the first terfenadine dose on day 0, and 12 hours after the evening terfenadine dose every seventh day and on randomly selected "unscheduled" days, wheal-and-flare areas were measured after intradermal injections of 0.01 ml of histamine phosphate (1.0 mg/ml and 0.1 mg/ml). On days 0, 28, and 56, six volunteers had skin tests hourly for 12 hours after the morning terfenadine dose. On all study days, serum terfenadine metabolite I concentrations were measured each time histamine skin tests were performed. On days 7, 14, 21, 28, 35, 42, 49, and 56, the mean areas of the histamine-induced wheals did not differ significantly from each other but were significantly decreased compared to the mean wheal area on day 0 (p less than 0.01). On these days, the mean areas of the histamine-induced flares also did not differ significantly from each other but remained significantly suppressed compared to the mean flare areas on day 0 (p less than 0.01). Wheal and-flare suppression was noted in all unscheduled histamine skin tests performed 12 hours after the evening terfenadine dose. In the subgroup of volunteers who had hourly tests, on day 0, the mean wheal-and-flare areas were significantly suppressed from 2 to 12 hours after the dose, with maximal wheal suppression occurring at 5 hours (p less than 0.05) and maximal flare suppression occurring from 3 to 9 hours (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2904932 TI - Hantaviruses are here in Scotland. PMID- 2904931 TI - The in vivo potency and selectivity of azelastine as an H1 histamine-receptor antagonist in human airways and skin. AB - Azelastine is a novel histamine H1 antagonist with putative antileukotriene activity in guinea pigs. With three different doses of oral azelastine, we have performed a dose-response study to determine its protective effect on the airways against histamine-induced bronchoconstriction in 12 patients with mild, atopic asthma. On 4 separate days, patients undertook standardized inhalation-challenge tests with increasing concentrations of histamine (0.03 to 32 mg/ml) 4 hours after placebo or azelastine, 4.4, 8.8, and 17.6 mg, administered double blind and in random order. On 2 additional days, patients underwent methacholine challenge tests after placebo or azelastine, 17.6 mg. Baseline FEV1 between treatment days and 4 hours after placebo and azelastine did not change significantly. The three doses of azelastine, 4.4, 8.8, and 17.6 mg, increased the concentration of histamine required to cause a 20% fall in FEV1 (PC20) from 0.16 mg/ml geometric mean (GM) after placebo to 1.98 (p less than 0.01), 8.8 (p less than 0.01), and 8.1 (p less than 0.01) mg/ml, respectively. GM potency ratios derived from the PC20 values obtained for each patient indicated that the three increasing doses of azelastine displaced the histamine dose-response curve to the right by factors of 12.8, 54.4, and 50.2. Azelastine had no effect on the airway response to methacholine with GM PC20 values of 0.16 and 0.19 after placebo and azelastine, 17.6 mg. Azelastine is a potent H1 histamine-receptor antagonist on human airways in vivo without demonstrable anticholinergic effect. PMID- 2904933 TI - The actions of L-glutamate at the postsynaptic membrane of the squid giant synapse. AB - The actions of L-glutamate on the postsynaptic membrane of the squid giant synapse were investigated using two methods of application: ionophoresis and bath perfusion. Bath perfusion of 10 mmoll-1 sodium glutamate did not produce an appreciable depolarization of the postsynaptic membrane but reversibly blocked the neurally evoked postsynaptic potential (PSP). The postsynaptic membrane depolarized when L-glutamate was applied ionophoretically. The sensitivity to glutamate application was not uniform, but sharply localized to sites which may correspond to synaptic contacts made by branching colaterals from the postsynaptic axon. The relationship between membrane potential and amplitude of the glutamate-activated postsynaptic potential (PSP) examined under current-clamp conditions was linear over the voltage range studied (-110 to -60 mV) with an extrapolated reversal potential of -36 mV. The amplitude of the glutamate activated PSP was reduced either by replacing Na+ in the external solution with Tris+ (Na+-free) or by raising the extracellular K+ concentration to 20 mmoll-1 and was abolished by removing both Na+ and Ca2+ from the bath solution. The PSP amplitude was insensitive to changes in the extracellular Mg2+ concentration. The extrapolated reversal potential of the glutamate PSP was shifted to more positive potentials in both Na+-free and raised-K+ bathing solutions and was unchanged by anion substitution. The depolarization induced by L-glutamate increased with increasing ionophoretic current and reached a maximum with large pulses. Double logarithmic plots of the coulomb dose-response relationship gave a limiting slope in the range 1.7-2.2, suggesting that two glutamate molecules are required for receptor activation. The time course of desensitization of the glutamate response was studied using a double-pulse method. The initial decrease in the ratio, PSP2/PSP1, is followed by a slower time-dependent recovery of the postsynaptic response with a time constant of 8.5 s. Prolonged perfusion of the squid giant synapse with concanavalin A failed to abolish desensitization of the glutamate evoked PSP. PMID- 2904934 TI - The public's view of mosquito problems in an organized control district. AB - Mosquito control programs provide abatement services to residents of urban, suburban and rural areas. The differing perceptions of these programs by residents of the Jefferson County Mosquito Control District (Texas) are examined using a mail survey. Mosquito problems start occurring earlier in the year for urban residents. The average number of bites per hour per night was 11. Rural residents used more self-administered control methods and incurred greater expenditures for these efforts than other residents. A majority of respondents recognized the effectiveness of the mosquito control district's current abatement efforts, but 56% supported greater use of nonchemical control methods. The study methods are expected to be useful in other areas to address similar problems. PMID- 2904935 TI - Oral transmission of eastern equine encephalomyelitis virus by a northern Indiana strain of Coquillettidia perturbans. PMID- 2904936 TI - The potential of mosquito-indigestible phytoplankton for mosquito control. PMID- 2904937 TI - Selected literature references to mosquitoes and mosquito-borne diseases. Part 1. PMID- 2904938 TI - Ground and aerial application of the asexual stage of Lagenidium giganteum for control of mosquitoes associated with rice culture in the Central Valley of California. AB - A series of ground and aerial applications of Lagenidium giganteum, a facultative fungal parasite of mosquito larvae, was made in rice fields and associated habitats in the Sacramento Valley, CA. Initial trials using ground applications of the fungus in 400 m2 plots indicated that asexually competent mycelium from 30 liters of fermentation beer per hectare was sufficient to control Culex tarsalis in rice field habitats. Two multi-hectare applications using a Micronair Atomizer were made at rates of mycelium from either 20 or 30 liters of fermentation beer per hectare. The lower application rate resulted in 40% confirmed infection of Cx. tarsalis and Anopheles freeborni sentinel larvae, while the higher application rate resulted in greater than 90% initial mortality of sentinel Cx. tarsalis and An. freeborni and 65% Aedes melanimon sentinel mortality. This was accompanied by a 10-fold decrease in indigenous populations of the 2 former species. PMID- 2904939 TI - Mosquito surveillance employing New Jersey light traps on Indian reservations in Iowa, Nebraska and South Dakota in 1984 and 1985. AB - A mosquito surveillance program was established in 1983 on Indian reservations in Iowa, Nebraska and South Dakota. Standard New Jersey light traps were operated on 12 reservations throughout the summer seasons in 1984 and 1985. Rainfall levels in general were higher than normal at all sites in 1984 but were lower than normal at most sites in 1985. Aedes vexans was the most abundant species collected on all reservations and Culex tarsalis second in abundance. Man-biting collections of mosquitoes near Brookings in 1984 reached 35 mosquitoes/5 minutes in early July and were largely composed of Ae. vexans, Ae. dorsalis and Ae. nigromaculis while numbers of Cx. tarsalis and An. quadrimaculatus were minor. During the same period in 1985, man biting collections averaged less than 5/5 minutes. PMID- 2904940 TI - Mosquito production and hydrological capacity of southeast Florida impoundments used for wastewater retention. AB - In Indian River County, Florida mosquito control impoundments, larval mosquito sampling and hydrological measurements demonstrated the importance of careful consideration of these factors when developing management plans for impoundments used for wastewater retention. Discharging secondarily treated wastewater into an impoundment resulted in only minor mosquito production. However, a treatment plant failure produced extremely high Culex densities in the impoundment. Average water loss rates in impoundments studied were due to evapotranspiration (0.25 cm/day) and percolation (0.38 cm/day). Greatest percolation (0.68 cm/day) was measured when the impoundments were maximally flooded. Under the conditions of this study, the impoundments can assimilate approximately 124 cm/year of wastewater (1.52 million liters/day) over a 50 ha area without overflows. PMID- 2904941 TI - Swarming and mating of the univoltine Aedes mosquitoes in the laboratory. PMID- 2904942 TI - Measurement of the effect of microsporidian pathogens on mosquito larval mortality under artificial field conditions. PMID- 2904943 TI - Efficacy of sustained-release formulations of Bacillus thuringiensis var. Israelensis and methoprene for control of Coquillettidia perturbans in Indiana. PMID- 2904944 TI - Habitat characteristics of Coquillettidia perturbans in central Florida. AB - Habitat characteristics were examined in two marshes and the littoral zones of two lakes in central Florida to determine their effect on the density and distribution of Coquillettidia perturbans. Larval and water samples were collected and habitat characteristics were recorded at monthly intervals for one year. Several significantly different physicochemical parameters were found between the marshes and lakeshores. Sites with dissolved oxygen less than 1.5 mg/liter (from October through May), pH less than 5.2, total alkalinity less than 6.0 mg CaCO3/liter, and orthophosphate less than 0.25 mg/liter were associated with significantly higher concentrations of Cq. perturbans. Arrow-arum, caric sedge, and maidencane were also associated with higher numbers of Coquillettidia. PMID- 2904945 TI - The host preferences of Culiseta inornata in southwestern Manitoba. AB - The capillary tube precipitin test was used to determine the host utilization patterns of Culiseta inornata in southwestern Manitoba. Ruminant blood was identified in 83.3% and equine blood in 15.8% of 1,036 positively reacting blood meals. Human, swine and avian blood accounted for 0.9% of these blood-meals and mixed blood-meals accounted for 1.5% of the total. Culiseta inornata preferentially fed on large mammals, and selection between cattle and horses reflected the relative abundance of these two hosts rather than a specific preference for either one. PMID- 2904946 TI - Field incidence of mosquito pathogens and parasites in central Alberta. AB - Ten pools and ponds were monitored on a weekly basis for presence of mosquito pathogens and parasites over a three year period near Edmonton, Alberta. Acari, fungi, Microsporidia and Peritrichida were found associated with mosquitoes. Percentage of collections with pathogens and parasites (prevalence) followed by the mean percentage infection within the samples, in parentheses (estimated % incidence) for the three year period were as follows: Coelomomyces psorophorae var. psorophorae 0.9(0.01-0.02), Culicinomyces clavisporus 1.2(0.09-0.2), Saprolegniales 50.1(15), Smittium sp. 23.0(4), Microsporidia 10.9(0.6-1.4), Peritrichida 43.4(30) and Acari 3.2(0.04). The high incidence of Saprolegniales may be a result of attack on stressed individuals under laboratory conditions. Several host and country records are reported. It is concluded that pathogens and parasites generally had little effect on the mosquito populations. PMID- 2904947 TI - Preliminary field trials with the entomopathogenic hyphomycete Tolypocladium cylindrosporum in central Alberta. AB - Conidia and blastoconidia of the pathogenic hyphomycete Tolypocladium cylindrosporum were applied to temporary and semi-permanent pools in central Alberta on 6 occasions. Infections were detected in the field only following application of blastoconidia; indications were that infections did not occur in the field following application of conidia. Most infections were detected only after holding field-collected immatures under laboratory conditions for up to 24 days. Five species of mosquitoes were found infected. Infections occurred in collections up to 29 days post-application with most mosquitoes dying as 4th instars. No infections were detected during subsequent years. Infection rates of up to 33% for blastoconidia and 55% for conidia were estimated. It is speculated that field-collected mosquitoes succumbed to the fungus as a result of the stress of transfer to laboratory conditions. PMID- 2904948 TI - Polycyclic aromatic compounds as phototoxic mosquito larvicides. AB - The phototoxicity of 2-acetylnaphthalene, 1-acetylnaphthalene, 1 naphthalenecarboxaldehyde, 9-xanthenone, 9-thioxanthenone, 9-methylanthracene, anthracene, alpha-terthienyl, pyrene and fluoranthene was tested with larvae of Aedes aegypti, Ae. taeniorhynchus and Culex quinquefasciatus. The larvae were exposed to the chemicals in the presence of sunlight for intervals from 1 to 6 hr and the corresponding LC50 values calculated. The LC50 values determined when the 6-hr exposure was followed by 18 hr in the dark range from over 10 ppm to below 0.001 ppm. Naphthalene derivatives were the least active while alpha-terthienyl, anthracene, 9-methylanthracene, pyrene and fluoranthene were the most phototoxic. PMID- 2904949 TI - Oviposition habitats of Psorophora columbiae in soybean fields of a Texas riceland agroecosystem. AB - Soil samples were collected over a 21/2-year period from microhabitats in fields planted to soybeans in Chambers County, TX, to study the oviposition behavior of Psorophora columbiae. An analysis of egg collection data gathered from the processing of 1,098 soil samples suggested that, during wet years, Ps. columbiae eggs tend to be scattered throughout soybean fields. During dry years, a greater abundance of eggs occur in the low areas of these types of fields. The data also suggested that oviposition by Ps. columbiae is concentrated in soil near the base of soybean plants rather than in open furrows between the rows of plants. PMID- 2904950 TI - The isolation of spiroplasmas from mosquitoes in Macon County, Alabama. AB - During the summer months of 1985, 1,298 adult mosquitoes comprising 21 species and 7 genera were collected in Macon County, Alabama. Mosquitoes were collected from four sections of the county with CO2-baited light traps. Spiroplasma cultures were isolated from two pools of 24 and 25 Aedes fulvus pallens, one pool of 22 Anopheles punctipennis and one pool of 7 Culex nigripalpus. Electron microscopic studies of the isolates revealed helical, wall-less cells. PMID- 2904951 TI - Recent pathogen and mosquito host records from Penang Island, Malaysia. PMID- 2904952 TI - Laboratory toxicity of a new benzoylphenylurea insect growth regulator (UC-84572) against mosquitoes and chironomid midges. PMID- 2904953 TI - Additional collection records for mosquitoes of Michigan. PMID- 2904954 TI - Vertical distribution of ovipositing Toxorhynchites moctezuma in Trinidad. PMID- 2904955 TI - An electrically heated membrane blood-feeding device for mosquito colony maintenance. PMID- 2904956 TI - Selected literature references to mosquitoes and mosquito-borne diseases. Part 2. PMID- 2904957 TI - The distribution of female mosquitoes about a flight barrier. AB - A 6.1 m long suction trap, with multiple air inlets located on its upwind, top, ends and downwind sides, was placed on a freely pivoting raft moored in a large borrow pit. Air inlets on the downwind side made larger captures than those on the upwind side. Inlets near the top edge of the trap captured larger numbers than those at the bottom. Larger proportions of Culex nigripalpus and Cx. erraticus accumulated behind the horizontal and vertical edges of the trap than did other species. Mosquitoes near the ends of the trap could choose whether to fly over or around the trap; most Cx. nigripalpus and Cx. erraticus flew over the trap while only Cx. pilosus favored going around the ends. Other species appeared to fly over and around the trap in approximately equal numbers. No evidence was found that flight patterns changed with differing wind velocities. PMID- 2904958 TI - Marking adult mosquitoes using an aerially applied fluorescent pigment. AB - A water soluble, fluorescent pigment was aerially applied to caged Culex quinquefasciatus adults in a south Louisiana marshland pasture. Mosquitoes held in cages on 1 m stakes were greater than 90% marked. This number was significantly greater (P less than 0.01) than the number of marked mosquitoes held in cages that were placed in dense vegetation (greater than or equal to 0.5 m high) near the ground surface (70% marked). In a second aerial test with caged Aedes sollicitans in an open, grassy area of the marshland pasture, the pigment marked 100% of the adult mosquitoes held in cages 1 m above the ground and 98% of the caged mosquitoes on the ground surface. Greater than 96% of the adults collected from an emerging population of Ae. sollicitans within the test area were marked as well as 100% of wild caught deer fly adults, Chrysops flavidus complex, in the test area. PMID- 2904959 TI - Dose-mortality responses of crawfish and mosquitoes to selected pesticides. AB - A study was conducted to determine the toxicities (LC50S) of several pesticides on the commercially important red swamp crawfish, Procambarus clarkii, and 3 mosquito species common in Louisiana ricelands--Anopheles quadrimaculatus, Culex salinarius and Psorophora columbiae. Pesticides tested in laboratory bioassays included Bacillus sphaericus, B. thuringiensis var. israelensis, bendiocarb, glyphosate, isostearyl alcohol, malathion, propoxur, resmethrin synergized with piperonyl butoxide (PBO) and thiobencarb. Isostearyl alcohol was the least toxic compound to crawfish, with a LC50 of greater than 10,000 ppm, while resmethrin + PBO (1:3 ratio) was the most toxic with a LC50 of 0.00082 ppm. The herbicides glyphosate and thiobencarb were the least toxic compounds for the mosquito species tested, while B. t. var. israelensis and resmethrin + PBO were the most toxic. PMID- 2904960 TI - A prospective field evaluation of an enzyme immunoassay: detection of eastern equine encephalomyelitis virus antigen in pools of Culiseta melanura. AB - A prospective field study was conducted to determine the sensitivity and specificity of an enzyme immunoassay (EIA) compared to virus isolation in cell culture for the detection of eastern equine encephalomyelitis (EEE) virus in naturally infected mosquitoes. A total of 10,811 adult female Culiseta melanura were collected in light traps during 1985 from four locations in Maryland. Eastern equine encephalomyelitis virus was isolated from 5 of 495 mosquito pools in African green monkey kidney and baby hamster kidney cell cultures. All five virus-infected pools were detected by the EIA, and all 490 uninfected pools were correctly scored as not containing virus. The EIA did not produce false positive or false negative results. Results support the assertion of previous researchers that the antigen detection EIA is a rapid, sensitive, specific, and simple alternative to traditional bioassays for the detection of EEE virus in mosquitoes. PMID- 2904961 TI - The sequential sampling of Psorophora columbiae larvae in rice fields. AB - Sequential sampling plans were developed for larval populations of Psorophora columbiae developing in rice fields during the growth of rice for a 2nd crop in southwestern Louisiana. Two types of plans were developed: 1) sequential counting plans to estimate the true mean of a population with a prespecified coefficient of variation and 2) sequential decision plans to assist in deciding whether the mean larval count/dip lies outside preselected upper or lower levels. The procedure by which the plans were developed consisted of: 1) conventional larval sampling by dipping along rice field levees that divided each field into pans; 2) counting the number of 2nd through 4th instar larvae observed in two dips taken at each sampling location; and 3) determination of the appropriate statistical parameters from which probability curves, number of samples required, and cumulative larval totals for specific sampling plans could be derived. Both sequential sampling plans are based upon distributions attendant to naturally occurring populations. PMID- 2904962 TI - Encapsulation of the mosquito fungal pathogen Lagenidium giganteum (Oomycetes:Lagenidiales) in calcium alginate. AB - The asexual stages (presporangial mycelia) of Lagenidium giganteum cultured on sunflower seed extract were encapsulated in calcium alginate and remained infective to mosquito larvae, Culex quinquefasciatus, after storage at 15 degrees C for up to 75 days. Survival and zoospore release from the encapsulated mycelia persisted for up to 24 days after immersion in water. Encapsulated sexual stages (oospores), held at 23-26 degrees C for up to 35 days or frozen for 8-10 days, were infective to mosquito larvae for up to 48 days after immersion in water and during that time over 50% of the oospores germinated. In outdoor pools, encapsulated mycelia gave 100% control of Cx. quinquefasciatus at 6-7 days after treatment while encapsulated oospores gave 100% control at 11 days posttreatment. PMID- 2904963 TI - The used tire trade: a mechanism for the worldwide dispersal of container breeding mosquitoes. AB - Modern transportation methods have facilitated an extensive trade in used tires at the national and international level. The history and reasons for this trade are described. Comprehensive data on United States imports and United States, Japanese, and Korean exports of used tires for the period 1978-85 reveal an unprecedented potential for the worldwide dispersal of important vector mosquitoes such as Aedes albopictus and Ae. aegypti. Other articles of commerce with similar potential may await recognition. PMID- 2904964 TI - A small habitat, larval mosquito sampler. PMID- 2904965 TI - Effectiveness of controlled-release personal-use arthropod repellents and permethrin-impregnated clothing in the field. AB - Two topical controlled-release personal-use arthropod repellent formulations of diethyl methylbenzamide (deet) and permethrin-impregnated clothing were tested on human volunteers in a tropical rain forest near Innisfail, Queensland, Australia. The field trials were arranged in a four-way factorial design which compared fabric types, permethrin treatment and repellent treatments over a 14-hour test period. An analysis of variance with each factor treated as a fixed effect indicated that treatment of the clothing with permethrin and use of topical repellents were effective in preventing bites. The controlled release formulations were not significantly better than the current U.S. Army formulation of deet under field conditions. The repellent formulations and the permethrin treated clothing used as one system provided better protection than the repellent formulations or permethrin-treated clothing used separately. PMID- 2904966 TI - Studies on bioassay of the entomopathogenic hyphomycete fungus Tolypocladium cylindrosporum in mosquitoes. AB - Larvae of Aedes aegypti, Ae. vexans and Culiseta inornata were used to study the pathogenicity of the hyphomycete fungus Tolypocladium cylindrosporum. Experiments consisted of continuous exposure of second-instar larvae to 5 concentrations of conidia at 10, 15, 20 and 25 degrees C. The 3 test species were susceptible at all temperatures tested. There was generally a direct relationship between dosage and pathogenicity in the host population, however linear relationships between probit mortality at 10 days and log dosage occurred in only 11 of 37 assays performed. In these 11 assays, median lethal concentrations were in the order of 10(4)-10(5) conidia/ml. Median lethal times were between 3 and 14 days. It was concluded that the present bioassay method for T. cylindrosporum is inadequate and needs major improvement. PMID- 2904967 TI - The distribution and larval habitat characteristics of Iranian Culicinae. AB - The distribution of the Iranian Culicinae is updated and reported by province. Larval habitat characteristics of each species, based on the information gathered throughout its range in Iran and at different times during the breeding season, are also presented. PMID- 2904968 TI - Habitat associations of mosquito and copepod species. AB - Copepods and mosquitoes were collected and identified over a 12-month period from three woodland ponds, discarded tires and a salt marsh. The species distribution of both mosquitoes and copepods varied among habitats and seasonally. Acanthocyclops vernalis was the predominant copepod in all of the habitats except the discarded tires, where Thermocyclops dybowskii was the predominant species. Amblyospora sp.-infected mosquitoes and copepods were found on several occasions in one of the woodland ponds and in the salt marsh. The results indicate that several copepod species have the potential to influence larval mosquito populations either directly as predators or indirectly as intermediate hosts of parasites. PMID- 2904969 TI - Efficacy of fenoxycarb (Pictyl) against Psorophora columbiae in Arkansas ricefields. AB - The IGR, fenoxycarb was effective against mosquitoes in both small rice plots and commercial ricefields in southeast Arkansas at the rate of 10 g AI/ha. It adequately controlled Psorophora columbiae populations. This compound shows excellent promise as a tool in effective IPM schemes against Ps. columbiae larvae in Arkansas rice fields by acting as a direct control, and possibly by indirectly increasing their vulnerability to natural controls. PMID- 2904970 TI - An evaluation of the mosquitofish, Gambusia affinis, and the inland silverside, Menidia beryllina, as mosquito control agents in California wild rice fields. AB - The mosquitofish, Gambusia affinis, and the inland silverside, Menidia beryllina, were evaluated in experimental, one-tenth hectare wild rice plots in Lake County, California, for their impact on densities of Culex tarsalis, Anopheles freeborni and Anopheles franciscanus. Gambusia affinis were tested at 0.6 and 1.7 kg/ha and the silversides at ca. 0.9 kg/ha. The silversides did not survive well in the rice field system and none of the silverside guts examined contained mosquito larvae. The mosquitofish increased steadily throughout the season and mosquito larvae were found in 9% of the fish dissected. Analysis of variance did not reveal significant differences among the mosquito populations in the 3 fish treatments and controls on any sampling date. More than 40 species of aquatic insects were collected and population densities of selected aquatic insects were similar among the 4 treatments. PMID- 2904971 TI - Psorophora columbiae larval density in southwestern Louisiana rice fields as a function of cattle density. PMID- 2904972 TI - Inheritance of orange pupa and phosphoglucomutase in the mosquito Armigeres subalbatus. PMID- 2904973 TI - Effectiveness of deet and permethrin, alone, and in a soap formulation as skin and clothing protectants against mosquitoes in Australia. PMID- 2904974 TI - Oviposition of Toxorhynchites theobaldi in different types of artificial containers in Mexico. PMID- 2904975 TI - In vitro study of the anticholinergic and antihistaminic activities of protopine and some derivatives. PMID- 2904976 TI - Neuroleptic malignant syndrome in a patient with Wilson's disease. PMID- 2904977 TI - Magnetic resonance imaging in an HTLV-I antibody positive patient with tropical spastic paraparesis. PMID- 2904978 TI - Synaptic connectivity of tyrosine hydroxylase immunoreactive nerve terminals in the striatum of normal, heterozygous and homozygous weaver mutant mice. AB - Striatal dopamine deficiency in weaver mutant mice is associated with loss of mesencephalic dopamine neurons. The maximum dopamine concentration in the striatum of weaver mutants is found on postnatal day 20, when it represents 50% of the control value. By day 180, it declines to 25% of the control value. Correspondingly, the number of nigral dopamine neurons is 58% of the normal number on day 20 and becomes 31% of the normal value by day 90. The aim of the present study was to examine whether dopamine axon terminals in the weaver striatum establish synaptic connections with postsynaptic neurons at the time when striatal dopamine concentration is at its peak value (i.e. on postnatal day 20), and if so, to compare the profile of synaptic connectivity of dopamine axon terminals found in the striatum of normal mice with that of heterozygous and homozygous weaver mutants. To that end, 20-day-old weaver homozygotes, along with age-matched weaver heterozygotes and wild-type mice were studied by electron microscopy after immunocytochemical labelling for tyrosine hydroxylase. A single micrograph of each of 1543 dopamine axon terminals was examined in total in the three genotypes; quantitative analyses of the relations of tyrosine hydroxylase immunoreactive nerve terminals were carried out in the dorsolateral striatum, which receives the dopamine projection from the substantia nigra proper. In all three genotypes, junctional contacts formed by tyrosine hydroxylase immunoreactive nerve terminals in the striatum were predominantly of the symmetrical type. In wild-type and heterozygous mice, the majority of contacts (92% and 91% respectively) were formed with dendrites and spines. In weaver mutant mice, the majority of contacts (87%) were also with dendrites and spines, but the proportion of axosomatic contacts was double that found in normal animals. The proportions of contacts that displayed junctional membrane specializations in single sections were 27% in wild-type mice, 29% in weaver heterozygotes, and 17% in homozygous weaver mutants. Taking into consideration that the plane of the section might not always have included the synaptic specialization, a stereological formula was applied. It was estimated that 85-89% of the contacts may be truly junctional in the striatum of normal and heterozygous mice, whereas only 53% may be junctional in the striatum of weaver homozygotes. The reduced incidence of junctional synapses in weaver homozygotes may suggest either inadequate synaptogenesis, or an early loss of synapses after their formation, or both.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2904979 TI - Reinstatement of synaptic connectivity in the striatum of weaver mutant mice following transplantation of ventral mesencephalic anlagen. AB - Ventral mesencephalic anlagen survive following grafting to the striatum of weaver mutant mice and reinnervate the dopamine-depleted basal ganglia of the recipients. The aim of the present study was to examine the pattern of connectivity established by graft-deriving dopamine afferents in the host striatum. Grafts were obtained from normal embryos at a gestational age of 14-15 days and implanted into a surgical cavity overlying the dorsal striatum of adult weaver recipients. Tissue was processed for electron microscopic immunocytochemistry using a primary antiserum against tyrosine hydroxylase. At the time of examination, recipient weaver mutants were 8.5 months old and the grafts had survived for 4.5 months. Grafts were found to contain an estimated 100 1000 tyrosine hydroxylase immunoreactive neurons. Tyrosine hydroxylase immunoreactive fibres, displaying characteristic varicosities, innervated the dorsal striatum to a depth of 1000 micron. In the non-grafted striatum, 8% of the contacts of tyrosine hydroxylase immunoreactive nerve terminals were junctional. That proportion contrasted with the corresponding value of normal animals, which is 27%. In the grafted striatum, 29% of the contacts were junctional. That percentage approximated the value found in normal animals. By applying a stereological correction, it can be estimated from those numbers that the true proportion of junctional contacts in the non-grafted striatum of 8.5-month-old mutants may be 26%, whereas that in the grafted side may be 91%, which is close to the normal situation. The majority of contacts in the reinnervated striatum (84%) were made with dendrites and spines. However, the proportion of total axosomatic contacts in the reinnervated striatum was twice as high as that found in the striatum of normal animals, and the proportion of junctional synapses was three times higher than that found normally. We conclude that: (1) in spite of a genetically determined degenerative process, the dorsal neostriatum of weaver mutant mice is receptive to synaptic investment by dopamine afferents originating in normal donor tissue. (2) In repopulating the denervated weaver striatum, graft deriving dopamine afferents display a connectional selectivity, i.e. they establish synaptic relations preferentially with those cellular domains that are normally innervated by dopamine nerve terminals. In this context, it is possible that dopamine fibres originating in the grafts invest postsynaptic sites that had either been vacated from the intrinsic dopamine input or had never received such an input. (3) The striatal connectivity following transplantation may retain features of immaturity as suggested by t PMID- 2904980 TI - Immunohistochemical characterization of osteoclasts and osteoclast-like cells with monoclonal antibody MB1 on paraffin-embedded tissues. AB - In this study we provide evidence that MB1, a newly developed monoclonal antibody which reacts with B lymphocytes and a proportion of T cells and monocytes, can be successfully used for the direct immunohistochemical identification of osteoclasts on paraffin-embedded surgical specimens. The antigen(s) recognized by MB1 is present at high density in the cytoplasm of osteoclasts of fetal bone and in the multinucleated cells of human giant cell tumour of bone (osteoclastoma), but is weakly expressed or absent in the giant cells of granulomas. MB1 is thus proposed as a new immunohistochemical marker for osteoclasts on paraffin-embedded material. PMID- 2904981 TI - Crossed testicular ectopia with bilateral duplication of the vasa deferentia: an unusual finding in cryptorchism. AB - A very unusual association of crossed testicular ectopia, with bilaterally duplicated vasa deferentia, was encountered in an otherwise normal 10-year-old boy who presented with bilateral cryptorchism. The left testis was palpable in the groin; the right was nonpalpable. Because of ductal fusion, both testes were brought down on the same side to avoid damage during separation, with placement of the testes in either hemiscrotum through a transseptal incision. PMID- 2904982 TI - Influence of relative humidity on the adhesive properties of a model interactive system. AB - The influence of relative humidity on the adhesive properties of model drug carrier interactive systems was investigated using the centrifuge method. The degree of adhesion was quantified by determining the S50 from the adhesion profile. High ambient humidity (greater than 40% r.h.) decreased the degree of interaction of three sulphonamide powders with model hydroxypropyl methylcellulose phthalate-coated glass bead carriers during blending. All drug carrier interactive systems displayed decreases in the degree of adhesion during storage. The extent and rate of the decreases increased with relative humidity and was interactive system-dependent. Preconditioning the powders to varying moisture contents produced contrasting results during blending, with one system showing a decrease in adhesion as the relative humidity increased, while the other's interactive capability increased. This increase was attributed to the enhancement of charging sites on the drug's powders surface by the adsorbed moisture. PMID- 2904983 TI - Buffer and pH effects on propranolol binding by human albumin and alpha 1-acid glycoprotein. AB - Propranolol binding to isolated human alpha-1-acid glycoprotein (AGP) and human albumin (HSA) was studied by equilibrium dialysis at 37 degrees C. With AGP (0.067%) and HSA (4%), total propranolol concentration was varied from 0.7 to 93,000 ng mL-1. Over this concentration range the percentage drug bound to HSA declined from 49 to 39% while that to AGP declined from 68 to 4%. Two classes of sites were identified on AGP with n1k1 = 8.50 X 10(4) M-1 and n2k2 = 3.12 X 10(4) M-1. With a pH 7.4 phosphate buffer, propranolol binding to AGP was greatest when the protein was initially dissolved in pH 7.4 water compared with pH 7.2 water or the phosphate buffer. Thus, the method of AGP solution preparation affected propranolol binding by this protein. For both AGP and HSA, greater drug binding was noted with phosphate buffers in comparison with a physiological buffer. With phosphate buffers, decreasing pH from 7.4 to 7.0 decreased propranolol binding by AGP, while decreasing pH from 7.7 to 7.4 had little effect. With HSA, the percent propranolol bound consistently decreased on lowering pH from 7.7 to 7.0. PMID- 2904984 TI - Retention and distribution of liposome-entrapped [3H]methotrexate injected into normal or arthritic rabbit joints. AB - Normal or arthritic rabbits were injected intra-articularly (i.a.) with free [3H]methotrexate ([3H]MTX) or liposomes containing [3H]MTX with [14C]cholesteryl oleate as a lipid marker. The distribution of 3H and 14C in the injected joint and other tissues was determined. Free [3H]MTX was rapidly cleared from the joint, 79% being excreted in the urine within 24 h of injection. Liposome entrapment retarded [3H]MTX clearance from the joint (P less than 0.001), 45.5% being recovered from the joint 24 h after injection. Uptake of liposomes by the inflamed synovium was lower than expected, 4% liposomal [3H]MTX injected being associated with the synovium after 24 h. Nevertheless, this was 40-fold greater than when free [3H]MTX was injected. Liposome entrapment should improve the efficacy and reduce the side effects of drugs injected directly into the joint cavity. PMID- 2904985 TI - The effects of salicylate concentration on the uptake of salicylate and cefmetazole into rat isolated small intestinal epithelial cells. AB - The uptake of salicylate into rat isolated small intestinal epithelial cells reached an equilibrium within 15 min, but that of cefmetazole alone did not. The presence of salicylate at concentrations greater than 50 mM accelerated the uptake of cefmetazole, which reached equilibrium within 5 min. At equilibrium, the uptake clearance of salicylate (mumol (g protein)-1 M-1 initial salicylate concn) was greater than that of cefmetazole. The uptake clearance of salicylate during the first several minutes was concentration-dependent, and a 'super uptake' clearance of salicylate, greater than equilibrium values, was observed when 100 mM salicylate was present. This indicates that some mechanism, other than a simple diffusion process, may be involved in salicylate uptake into these cells. PMID- 2904986 TI - Influence of 5-tridecylpyrazole-3-carboxylic acid, a new hypolipidaemic agent, on cholesteryl ester formation in rabbit intestinal mucosa. AB - The comparative effects of 5-tridecylpyrazole-3-carboxylic acid (TDPC), beta sitosterol and melinamide on the esterification of cholesterol (CH) have been investigated in rabbit intestinal microsomes and cytosol in-vitro. The three agents did not show an effect on cholesteryl ester formation by cholesterol esterase (CEase). TDPC and beta-sitosterol did not affect cholesteryl oleate formation from oleoyl CoA by microsomal acyl CoA:cholesterol acyltransferase (ACAT), whereas melinamide significantly inhibited cholesteryl oleate formation. TDPC significantly inhibited the incorporation of oleic acid into cholesteryl oleate, which is associated with acyl CoA synthetase (ACS) plus ACAT in mucosal microsomes, at a concentration of 20-100 microM. On the other hand, 5 tridecylpyrazole-3-carbinol (TDPC-OH) a congener of TDPC, and beta-sitosterol did not show any effect. From these results, it is demonstrated that carboxylic moiety of TDPC is necessary to inhibit ACS in-vitro. According to the kinetic analytical results, it is suggested that TDPC acts as a competitive inhibitor of ACS. These results suggest that the inhibitory effect of TDPC on cholesteryl ester formation may be mediated by an inhibition of ACS activity. It is apparent from the data presented that there are substantial differences between TDPC, beta sitosterol and melinamide with respect to their action on cholesteryl ester formation in rabbit intestinal mucosa. PMID- 2904987 TI - Paracetamol confers resistance to ethanol-induced gastric mucosal damage in rats. AB - Paracetamol given orally or subcutaneously did not produce any observable gastric mucosal damage, nor did it change the acidity of the residual secretion in rat stomachs. However, it delayed the gastric emptying rate and increased the residual volume of gastric secretion. Pretreatment with paracetamol 250 mg kg-1 significantly prevented ethanol-induced gastric ulceration. Although it did not influence ethanol-stimulated acid secretion, it increased the mucosal mucus content in the ethanol-treated animals. The findings suggest that the protective mechanism of paracetamol against ethanol-induced damage is likely to be due to improved gastric mucosal integrity, through an increase in the adherent mucosal mucus which protects the underlying delicate cellular structures. PMID- 2904988 TI - The biphasic effects of centrally and peripherally administered caffeine on ethanol-induced motor incoordination in mice. AB - The possible biphasic effect of caffeine on acute ethanol-induced motor incoordination by rotorod evaluation was investigated in mice. Caffeine in various doses was administered intracerebroventricularly (i.c.v.) to mice implanted with permanent indwelling stainless steel guide cannulae and intraperitoneally (i.p.) to non-cannulated animals. A motor incoordinating test dose of ethanol, 2 g kg-1, was given i.p. in both cases. Caffeine less than 25 micrograms administered i.c.v., dose-dependently attenuated while 75 micrograms i.c.v. potentiated ethanol (i.p.)-induced motor incoordination. Similarly, caffeine less than 20 mg kg-1 given i.p., dose-dependently attenuated while 62.5 mg kg-1 potentiated ethanol (i.p.)-induced motor incoordination. The data obtained demonstrated that caffeine given either i.c.v. or i.p. exerted biphasic effects on ethanol-induced motor incoordination. The data also suggested that caffeine antagonized ethanol-induced motor micrograms i.c.v.; less than 20 mg kg 1 i.p.) caffeine is well known to display high affinity for adenosine binding sites. Therefore, the present investigation lends further support to our earlier suggestion that adenosine may be involved in the motor impairing effect of ethanol. PMID- 2904989 TI - Inhibition of the multiplication of enveloped and non-enveloped viruses by glucosamine. AB - Glucosamine can inhibit the development of viral cytopathogenic effect and the production of infective viral particles of both enveloped and non-enveloped viruses. The extent of antiviral activity is dependent on drug concentration, composition of the culture medium and type of cell host. PMID- 2904990 TI - Actions of buspirone in a putative model of anxiety in the mouse. AB - In a two-compartment box divided into a dark area and a brightly illuminated white area, mice taken from a dark environment showed aversion to the light and exhibited preference for exploratory rearings and line crossings in the black area. The peripheral administration of buspirone, and its injection into the dorsal raphe nucleus, lead to an increased time spent in the white area associated with enhanced exploratory behaviour with a decreased incidence of rearings and line crossings in the black section. In contrast, the injection of 5 hydroxytryptamine and 2-methyl-5-hydroxytryptamine into the dorsal raphe nucleus increased exploratory behaviour in the black section with decreased activity in the white area: the effects of 2-methyl-5-hydroxytryptamine were antagonized by buspirone administered peripherally. Ritanserin, methysergide, metergoline and cyproheptadine failed, in non-sedative doses, to influence exploratory behaviour in the two-compartment system and ritanserin and methysergide also failed to antagonize the effects caused by 2-methyl-5-hydroxytryptamine. It is concluded that in the mouse model the ability of buspirone to reduce the aversive response to a brightly illuminated area may reflect an anxiolytic action, that the dorsal raphe nucleus may be an important locus of action, and that the effects of buspirone may reflect an interaction at 5-hydroxytryptamine receptors. PMID- 2904991 TI - Effects of an extract of feverfew on endothelial cell integrity and on cAMP in rabbit perfused aorta. AB - Extracts of feverfew inhibit platelet aggregation and secretion of granular contents from platelets and other cells. They also modify the interaction of platelets with collagen substrates: feverfew extracts inhibit both platelet spreading and formation of thrombus-like platelet aggregates on the collagen surface. We have now investigated the effect of an extract of feverfew on the vessel wall using rabbit aortas that were perfused with a physiological salt solution in-situ. Addition of feverfew extract to the perfusion medium protected the endothelial cell monolayer from perfusion-induced injury and led to a reversible increase in the cAMP content of aorta segments. The results indicate that feverfew may have a vasoprotective effect in addition to its effects on platelets. PMID- 2904992 TI - Characterization of the sphericity of particles by the one plane critical stability. AB - A method has been developed to characterize the roundness of particles in terms of the angle necessary to tilt a plane such that the particles would roll, the 'one plane critical stability'. The method is based on determination of the centre of gravity of the particle from a digitized image of the coordinates of its outline and computing the angle necessary to incline a plane such that the centre of gravity moves outside the boundary of the particle. The method is particularly applicable to differentiate between the various shapes formed during the production of spherical granules by extrusion/spheronization. PMID- 2904993 TI - Facile plasma-catalysed degradation of penicillin alkyl esters but with no liberation of the parent penicillin. AB - The methyl ester and some glycolamide esters of benzylpenicillin and ampicillin were shown to be rapidly degraded by human plasma at 37 degrees C with no parent penicillin being produced. The plasma-catalysed degradation which was also observed in rat plasma proceeds most likely through hydrolytic cleavage of the beta-lactam bonds of the penicillin esters and is suggested to be due to the presence of an ester-specific beta-lactamase in plasma. The results show that the failure of simple alkyl esters of penicillins to function as prodrugs is not due to a high enzymatic stability of the esters, as widely believed, but rather to a pronounced susceptibility to undergo hydrolytic cleavage of their beta-lactam ring in-vivo. Since double ester prodrugs of penicillins, such as the pivaloyloxymethyl ester of ampicillin, are readily hydrolysed in plasma to yield the parent penicillin although at a rate lower than e.g. that of inactivation of a simple methyl ester, the plasma enzyme apparently attacking the beta-lactam bond of penicillin esters appears to have a high degree of specificity for the ester structure. PMID- 2904994 TI - Sustained anti-adherence activity of taurolidine (Taurolin) and noxythiolin (Noxyflex S) solutions. AB - Taurolidine (2% w/v) and noxythiolin (1% w/v and 2.5% w/v) solutions inhibit the adherence in-vitro of Escherichia coli and Staphylococcus aureus to human epithelial and fibroblast cells. This effect, demonstrable after 30 min exposure of cells to test drugs, persists after removal of the active compound. Significantly reduced adherence of bacteria is apparent for 5 h after taurolidine treatment and for 6 h after treatment with 2.5% noxythiolin. Anti-adherence activity of taurolidine and noxythiolin may contribute to the observed clinical efficacy of these agents. PMID- 2904995 TI - The effect of ciprofibrate on gastric secretion in the rat. AB - The potential of ciprofibrate to inhibit gastric secretion has been investigated in the rat. A significant gastric antisecretory effect was observed following a single oral administration of 300 and 500 mg kg-1 and following a single intraduodenal dose of 100, 300 and 500 mg kg-1. The toxicological significance of this finding is discussed in the light of a spate of recent publications linking changes in gastric morphology with hypergastrinaemia produced as a secondary effect of inhibition of acid secretion. PMID- 2904996 TI - Verapamil and nifedipine effects on gastric acid secretion and ulcer formation in rats. AB - The calcium channel antagonists verapamil and nifedipine were examined for their effects on conscious basal gastric acid output, stress ulcer formation and on ethanol-induced ulcers. Both compounds significantly reduced gastric acid secretion, however verapamil did so in a dose-related manner. Both verapamil and nifedipine significantly attenuated stress gastric ulcer formation. Nifedipine, at a dose of 32.0 mg kg-1, virtually abolished stress ulcers. Verapamil exacerbated, while nifedipine, at 32.0 mg kg-1, attenuated ethanol-induced gastric ulcers. The differential gastrointestinal effects of these calcium channel antagonists support the existence of multiple classes of calcium channels in the gut and suggest an important role for intracellular calcium and hence, its blockade, in gastric pathophysiology. PMID- 2904997 TI - Protective effect of salicylate against 2,4-dinitrophenol-induced protein thiol loss in the small intestine of rats. AB - The effect of the content of protein thiols and non-protein thiols in the tissue of the rat small intestinal loop on the absorption of cefmetazole has been investigated. 2,4-Dinitrophenol (DNP), at a concentration of 500 microM, caused rapid protein thiol loss, followed by non-protein thiol loss, along with a decrease of cefmetazole absorption by the intestine. The coadministration of 75 mM salicylate with DNP inhibited the effect of DNP on protein thiols and cefmetazole absorption but not on non-protein thiol loss by DNP. PMID- 2904998 TI - Brain monoamines during carrageenan-induced acute paw inflammation in rats. AB - Paw inflammation was induced in rats by sub-plantar administration of carrageenan. Significant inflammatory oedema was observed 1 h later and the peak effect was noted between 3-4 h. The oedema was markedly reduced after 12-24 h. Steady state levels of whole brain and hypothalamic monoamines were estimated spectrofluorometrically during the course of the carrageenan-induced paw inflammation. In addition, the rate of accumulation of the brain 5 hydroxytryptamine (5-HT) and noradrenaline (NA) was assessed in clorgyline pretreated rats during the inflammation. The whole brain and hypothalamic concentrations of 5-HT and NA were augmented during the early phase of the inflammation, but fell below control values when peak inflammation was achieved. Thereafter, the monoamine levels tended to normalize by 24 h when the inflammation had virtually subsided. On the contrary, whole brain and hypothalamic dopamine levels remained largely unaffected. The rate of accumulation of brain 5-HT and NA were enhanced during carrageenan inflammation, indicating that the turnover of these monoamines is augmented during the inflammatory process. The results suggest that acute peripheral inflammation may significantly affect central 5-HT and noradrenergic activity in rats. PMID- 2904999 TI - Actions of amrinone and milrinone on the guinea-pig ileum. AB - The pharmacological activity of the cardiotonic agents amrinone and milrinone has been examined on the isolated guinea-pig ileum. Both compounds antagonised the presynaptic inhibitory action of adenosine on electrically evoked contractions, milrinone being the more potent. Higher concentrations of amrinone or milrinone produced contractions of the ileum which were prevented by atropine. Contractile responses to adenosine 5'-monophosphate were not inhibited by atropine. It is concluded that amrinone and milrinone can antagonise some effects of purines but this does not represent their only pharmacological action. PMID- 2905000 TI - Dopamine-mediated behaviour following chronic treatment with B-HT 920. AB - Following subchronic (5-day) dosing with B-HT 920 (2-amino-6-allyl-5,6,7,8 tetrahydro-4H-thiazolo(4,5-d)azepine (1 mg kg-1 day-1 i.p.) in rats there was a significant increase in both apomorphine-induced motor activity and stereotypy. On continued B-HT 920 treatment, however, the enhancement of apomorphine motor activity faded into insignificance but the increase in stereotypy persisted beyond 15 days. The results are discussed in terms of dopamine autoreceptor tolerance, postsynaptic D2 supersensitivity and possible differential effects in different brain loci on the above two receptor sub-classes. PMID- 2905001 TI - McN-5652: a highly potent inhibitor of serotonin uptake. AB - McN-5652 is one of a series of substituted pyrrolo-isoquinolines that, as a group, potently inhibit the uptake of one or more of the monoamines, norepinephrine, serotonin and dopamine. McN-5652 is characterized by exceptionally high potency as an inhibitor of the uptake of serotonin by rat brain synaptosomes in vitro (Ki approximately 0.6 nM) and ex vivo (ED50 approximately 2 mg/kg p.o.). The high potency of McN-5652 as a serotonin uptake inhibitor in vivo is indicated further by the low doses required to potentiate L 5-hydroxytryptophan-induced head twitches in mice (ED50 = 0.4 mg/kg 2 hr after p.o. dosing) and the serotonin syndrome in rats (ED50 = 1.5 mg/kg 2 hr after p.o. dosing). McN-5652 also potently inhibited the synaptosomal uptake of norepinephrine (Ki approximately 3 nM) and was a moderately potent inhibitor of the synaptosomal uptake of dopamine (Ki approximately 40 nM). McN-5652 inhibited tetrabenazine-induced ptosis in rats and mice but was much less effective in blocking the sedation caused by tetrabenazine. In rats, McN-5652 did not induce the stereotyped behavior often caused by dopamine agonists and inhibitors of dopamine uptake. Receptor binding experiments indicated that McN-5652 has a weak affinity for serotonin 5-HT2 and alpha-1 adrenergic receptors (apparent Ki approximately 200 nM) and a very low affinity for dopamine D1 and D2 receptors, serotonin 5-HT1, alpha-2 adrenergic, muscarinic and gamma-aminobutyric acid-A receptors. Experiments using the guinea pig ileum indicate that McN-5652 is a weak, noncompetitive antagonist of histamine. PMID- 2905002 TI - Pharmacological profile of SCH39166: a dopamine D1 selective benzonaphthazepine with potential antipsychotic activity. AB - SCH39166 [(-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl- 5H benzo[d]naptho-(2,1-b)azepine] is a benzonaphthazepine that has been evaluated as a selective D1 dopamine receptor antagonist. In vitro, SCH39166 (Ki = 3.6 nM) inhibited the binding of [3H]SCH23390 (a D1 specific compound) and blocked dopamine-stimulated adenylate cyclase (Ki = 9.1 nM); in contrast the Ki for SCH39166 to displace [3H]spiperone (D2) was greater than 1 microM and its Ki vs. [3H]-ketanserin (5-hydroxytryptamine2) binding was greater than 300 nM. In vivo, SCH39166 inhibited both rat and squirrel monkey conditioned avoidance responding (minimal effective dose = 10 and 1.78 mg/kg p.o., respectively) and had a duration of at least 6 hr in both species. In addition, SCH39166 antagonized apomorphine-induced stereotypy in rats (minimal effective dose = 10 mg/kg p.o.). These in vivo actions of SCH39166 are similar to the activity of typical dopamine antagonists. However, in contrast to D2-selective antagonists, SCH39166 failed to increase plasma prolactin levels, did not block apomorphine-induced emesis in the dog and had minimal effects on the striatal levels of homovanillic acid or dihydroxyphenylacetic acid. Furthermore, although immobility was seen after p.o. administration of SCH39166 using the inclined screen test, the drug did not cause catalepsy at doses up to 10 times its minimal effective dose in the rat conditioned avoidance response test. Additionally, SCH39166 inhibited apomorphine induced climbing at lower doses than it inhibited apomorphine-induced sniffing in mice. The results from these latter two tests suggest that SCH39166 may have a reduced liability to produce extrapyramidal side effects. Therefore, based on this profile of activity, SCH39166 is a selective D1 dopamine receptor antagonist both in vitro and in vivo. Additionally, because this compound is longer acting in the primate than previously available D1 antagonists, it has potential utility as a clinically useful drug. PMID- 2905003 TI - Mechanism of the lipid-mobilizing effect of alpha-2 adrenergic antagonists in the dog. AB - Alpha-2 adrenergic antagonists may constitute putative antiobesity agents. These drugs may act: 1) by blockade of the antilipolytic alpha-2 adrenoceptor on fat cell membranes and 2) by activation of the sympathetic adrenergic system (blockade of central and presynaptic alpha-2 adrenoceptors). Studies were undertaken in the dog, a species possessing fat cell alpha-2 and beta adrenoceptors in order: 1) to define and compare the metabolic and endocrinological impacts of recently discovered alpha-2 antagonists [idazoxan and SK&F 86,466 (6-chloro-N-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine)] and of an older one (yohimbine) and 2) to dissociate the contribution of the noradrenergic activation from a postsynaptic action on fat cell and endocrine pancreas alpha-2 adrenoceptors. Binding studies showed that the three compounds have similar affinities for the alpha-2 adrenoceptor on both cerebrocortical and fat cell membranes. Their ability to suppress the antilipolytic effect of an alpha-2 agonist [UK-14,304 (5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline)] on isolated fat cells was equivalent. Yohimbine perfusion induced a dose-dependent increase in plasma nonesterified fatty acids (NEFA) and immunoreactive insulin concentrations. At equivalent doses, the three alpha-2 adrenergic antagonists induced NEFA mobilization, increase in immunoreactive insulin and norepinephrine plasma levels with an order of potency: yohimbine much greater than idazoxan greater than or equal to SK&F 86,466. The weakest effect on sympathetic activation was with SK&F 86,466. The effects of yohimbine were suppressed completely by pretreatment with propranolol. Clonidine infusion reduced NEFA levels in dogs. Yohimbine but not SK&F 86,466 abolished completely this lowering effect of clonidine on NEFA and glycerol levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2905004 TI - Intraseptal microinjection of adrenocorticotropic hormone1-24 antagonizes pentobarbital-induced narcosis and depression of hippocampal cholinergic activity. AB - Intracerebroventricular or intraseptal microinjection of adrenocorticotropic hormone1-24 (ACTH1-24) to pentobarbital-anesthetized rats and rabbits produced shortening of the duration of narcosis. This analeptic effect was blocked by atropine, indicating the central cholinergic nature of the response. ACTH1-24 also increased hippocampal sodium-dependent high affinity choline uptake activity that had been depressed by the barbiturate. Naloxone-pretreatment also blocked the analeptic and cholinergic activating properties of ACTH1-24. These results suggest that intraseptal ACTH1-24 produces its analeptic effect by activating a hippocampal cholinergic arousal system. PMID- 2905006 TI - Modification of the repair of potentially lethal damage in plateau-phase Chinese hamster cells by 2-chlorodeoxyadenosine. PMID- 2905005 TI - Alpha adrenoceptor subtypes and receptor reserve in human versus canine saphenous vein: sensitivity to blockade by nitroglycerin. AB - The purpose of this investigation was to determine the subtypes of alpha adrenoceptors present in human saphenous vein and to determine if there is a large receptor reserve for phenylephrine as has been demonstrated in canine saphenous vein. The subtypes of alpha adrenoceptors found in isolated human saphenous vein were determined using selective alpha-1 and alpha-2 adrenoceptor agonists and antagonists. Prazosin, a selective alpha-1 antagonist, produced a parallel shift of the concentration response curve to phenylephrine, a selective alpha-1 agonist, with no significant reduction in the maximal response. Yohimbine, a selective alpha-2 antagonist, produced a parallel shift of the concentration response curve to B-HT 920, a selective alpha-2 agonist, with no reduction in the maximal response. The pA2 values obtained for prazosin and yohimbine in human saphenous vein agreed closely with corresponding values obtained in canine saphenous vein. These results demonstrate that both alpha-1 and alpha-2 adrenoceptors exist in human saphenous vein. Phenoxybenzamine (10(-7) M), an irreversible alpha-1 adrenoceptor antagonist, markedly reduced the maximal response produced by phenylephrine, an agonist with high intrinsic activity, with no significant shift in the concentration response curve in human saphenous vein, suggesting that there was little or no alpha-1 receptor reserve for phenylephrine. The sensitivity of alpha-1 versus alpha-2 adrenoceptor-mediated vasoconstrictor responses to nitroglycerin were compared in human and canine saphenous veins. In both species, nitroglycerin blocked the vasoconstrictor response produced by stimulation of alpha-2 adrenoceptors to the same degree.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2905007 TI - Clinically important interactions of nonsteroidal antiinflammatory drugs with other medications. AB - While many interactions between nonsteroidal antiinflammatory drugs (NSAID) and other drugs are reported, only a limited number of them are clinically important. These interactions can be divided into those explainable on mainly pharmacokinetic grounds, those explainable on interactions between pharmacokinetics and pharmacodynamics, and those that remain unexplained. Among those explainable on primarily kinetic grounds are interactions of NSAID with antacids, anticoagulants, hypoglycemics, methotrexate, lithium, probenecid, and phenytoin. More complex interactions between dynamics and kinetics are those relating NSAID interactions with diuretics, beta-blockers, other NSAID, and some anticoagulants. Finally important interactions whose causes are not understood include those between aspirin and corticosteroid, indomethacin and triamterene, and flurbiprofen with certain anticoagulants. PMID- 2905008 TI - Passage of host immunoglobulin G from blood meal into hemolymph of selected mosquito species (Diptera: Culicidae). PMID- 2905009 TI - Effectiveness of personal protection against mosquitoes in Alaska. PMID- 2905010 TI - Epizootiology of eastern equine encephalitis virus in upstate New York, USA. VII. Virus surveillance 1978-85, description of 1983 outbreak, and series conclusions. PMID- 2905011 TI - Gut content analysis of mosquito larvae (Diptera: Culicidae) using DAPI stain and epifluorescence microscopy. PMID- 2905012 TI - Clinical, microbiological and antibiotic susceptibility patterns of diarrhoea in Korem, Ethiopia. AB - Two hundred patients with diarrhoea in a rehabilitation camp in Ethiopia were studied in October 1985 to determine the presence of pathogens in the stool and their susceptibility to antibiotics. A total of 42 (21.1%) patients had a positive culture with enterobacteriaceae, the isolation rate was 15.6% for Escherichia coli, 3.5% for Shigella spp. and 2.01% for Salmonella spp. In-vitro antibiotic resistance was frequent among the 42 isolates: 53% of E. coli strains were found to be resistant to ampicillin, 47% to chloramphenicol, 30% to co trimoxazole and 67% to tetracycline. Of the seven Shigella, three were resistant to chloramphenicol and four to tetracycline. Multidrug resistance (two or more antibiotics) was observed in 52.3% of the 42 isolates. The protocols used for the screening of dysenteric patients for Shigella spp. or Salmonella spp. were found to be specific but poorly sensitive. The opposite was observed for amoebiasis and giardiasis. The responsibility of widespread use of common oral antibiotics is discussed as one of the major factors of antibiotic resistance occurrence at Korem. PMID- 2905013 TI - Sequence heterogeneity of human liver arginase cDNAs and restriction fragment length polymorphism of the gene locus. PMID- 2905014 TI - Restriction fragment length polymorphisms on the short arm of X chromosome among the Japanese population. PMID- 2905015 TI - [Education and training of assistants in ophthalmic microsurgery]. PMID- 2905016 TI - [On terminal care. Trials at holding terminal care conferences superseding the ward distinction at the Kitasato Hospital]. PMID- 2905017 TI - [Hemodynamic disorders in acute poisoning by a mixture of psychopharmacological preparations and their treatment]. PMID- 2905018 TI - Dibutyryl cyclic adenosine monophosphate inhibits pulmonary vasoconstriction. AB - The effects of the cell-permeable dibutyryl derivative of cyclic AMP on the vascular reactivity of isolated perfused rat lungs were examined. In lungs perfused with homologous blood, pulmonary arterial infusion of db-cAMP (30 micrograms/min) inhibited hypoxia-induced vasoconstriction (IC50 = 6.3 X 10(-5) M) and vasoconstriction due to bolus injection of angiotensin II (IC50 = 8.2 X 10(-5) M). Cyclic AMP phosphodiesterase inhibition by aminophylline acted synergistically with db-cAMP in the reduction of hypoxia-induced vasoconstriction. Somatostatin, an inhibitor of adenylate cyclase, prevented the decay of hypoxic vasoconstriction typically observed in isolated lungs, suggesting that a rise in intracellular cAMP may occur during hypoxic vasoconstriction as a consequence of activation of the adenylate cyclase. In lungs perfused with cell and protein-free salt solution, db-cAMP inhibited both initial and prolonged vasoconstriction following bolus injection of 2 microgram leukotriene C4. Thus, db-cAMP inhibited pulmonary vascular reactivity nonspecifically. PMID- 2905019 TI - [Immunology and insulin-dependent diabetes mellitus--a review]. PMID- 2905020 TI - [Beta blockade after myocardial infarction or not?]. PMID- 2905021 TI - [A congress on Fallot's tetralogy]. PMID- 2905022 TI - Effect of captopril on ventricular dilatation after anterior myocardial infarction. PMID- 2905024 TI - [Neuroleptics as anxiolytic and antidepressive agents]. PMID- 2905025 TI - [The effect of inhalation treatment with corticosteroids and beta sympathomimetics on bronchial sensitivity in children with asthma]. PMID- 2905023 TI - Activation and repression of transcription by homoeodomain-containing proteins that bind a common site. AB - The product of the fushi tarazu (ftz) gene is shown to be a site-dependent activator of transcription. In vitro-defined binding sites act as ftz-dependent enhancers in cultured cells. Another homoeodomain-containing protein, the engrailed gene product, competes for homoeodomain-binding sites and counteracts ftz activation. PMID- 2905026 TI - [Selective augmenting effect of oxy-Hb on the contractions of cerebral arteries elicited by various vasoactive substances]. AB - Serotonin (5-HT), histamine (HA), angiotensin II (ATII), prostaglandin F2 alpha (PGF2 alpha) and thromboxane A2 (TxA2) are known as vasoactive substances, each producing a characteristic contraction of cerebral arteries. These contractions are considered to be mediated by their specific receptors. Recent studies suggest that the activations of these receptors primarily stimulate the phospholipase C and/or phospholipase A2 localized within the same membrane. Stimulation of these enzymes consequently induces production of the second or third messengers such as inositol triphosphate (IP3), diacylglyceride (DAG), arachidonic acid (AA), and ultimately various prostaglandins. The present study is to examine how oxyhemoglobin (Oxy-Hb), another vasoactive substance, can modify these receptor mediated contractions, and to compare the effects on high K+-, caffeine-and 1 oleoyl-2-acetyl-rac-glycerol (OAG)-induced contractions which are not mediated by the receptors on the cytoplasmic membrane. Helical strips of the bovine middle cerebral arteries (M2) were mainly used in this experiment, and the changes in muscular tensions during isometric contractions were recorded on the polygraph. 5 HT, HA, ATII, PGF2 alpha and cTxA2 (carbocyclic thromboxane A2) were used for each receptor activation. Indomethacin (IDM), a cyclooxygenase inhibitor and 2 nitro-4-carboxyphenyl-n, n-diphenyl-carbamate (NCDC), a phospholipase C inhibitor were used to analyze a possible acting site of Oxy-Hb in modifying these reseptor mediated enzyme reactions. The results obtained are summarized as follows. (1) All contractions induced by either 5-HT, PGF2 alpha, cTxA2, HA or ATII (concentrations less than 10(-6) M) were markedly augmented as much as 4-8 times the normal, when they were examined in the presence of 10(-5)M Oxy-Hb.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2905027 TI - Evidence that there is no direct correlation between alpha 2-adrenoceptor antagonism and inhibition of voltage-dependent sodium channels. AB - Electrophysiological and biochemical evidence suggests that the voltage-dependent sodium channel is the site of local anesthetic action, and that there is pharmacological similarity between alpha-adrenoceptors and Na+-channels. Yohimbine, a non-selective alpha 2-adrenoceptor antagonist, with a structure similar to that of cocaine affects the sodium channel by a mechanism different from that of other local anesthetics including cocaine. Some structural analogues of yohimbine -berbane compounds- were found to be potent and selective alpha 2 adrenoceptor antagonists. In this work the local anesthetic properties of two berbane compounds (6c and 6d (CH-38083) from the paper of Vizi, Toth, Somogyi, Szabo, Harsing and Szantay, 1987) were examined and compared to those of yohimbine in vitro on scorpion venom-enhanced specific binding of [3H]batrachotoxinin A 20-alpha-benzoate [( 3H]BTX-B) to the voltage-sensitive sodium channel and on the veratridine-induced depolarization measured by the uptake of [3H]trimethylphenylphosphonium ion [( 3H]TPMP+) in mouse brain cortex. Both of the compounds inhibited the [3H]BTX-B binding with an IC50 of (approximately) 150 microM, which is more than four orders of magnitude higher than the concentration required for antagonism of a presynaptic alpha 2 adrenoceptor (7 nM). They are 15 times less potent in inhibiting [3H]BTX-B binding and 2.5 times less potent in inhibiting veratridine-induced depolarization than yohimbine. PMID- 2905028 TI - [Use of somatostatin in the therapy of acute pancreatitis]. PMID- 2905029 TI - Increased blood flow enhances axon regeneration after spinal transection. AB - It is not known whether increasing the amount of blood flow to axotomized fibers in mammalian CNS can result in more robust sprouting. To find out, an intact pedicled omentum was surgically transposed to cover a collagen matrix gel used to bridge the transected cat spinal cord stumps. Control animals were similarly treated but did not receive the pedicled omentum. Twelve weeks after cord transection, animals receiving the pedicled omentum showed a 66% spinal cord blood flow increase over animals that did not. Moreover, treatment with the pedicled omentum increased the density of regenerating adrenergic axons 10-fold over the control group. These findings indicate that boosting flow with an omental graft to the collagen bridge site results in robust axonal outgrowth of spinal transected nerve fibers. PMID- 2905031 TI - Abstracts of the third meeting of the Italian Society of Neuroscience. Bologna, Italy, November 27-30, 1988. PMID- 2905030 TI - Glutamate induces a depolarization of adult rat dorsal root ganglion neurons that is mediated predominantly by NMDA receptors. AB - The effects of glutamate, glutamate receptor agonists and substances that affect glutamate responses were studied, using the whole-cell patch-clamp technique, on neurons isolated from adult rat dorsal root ganglia. In current-clamp, glutamate (100 microM) or the excitatory amino acid receptor agonist N-methyl-D-aspartate (NMDA; 10 or 100 microM) induced membrane depolarization. Under voltage-clamp, these compounds induced an inward current that was voltage-dependent in the presence of Mg2+. The NMDA-induced current was inhibited by the NMDA receptor antagonist D,L-2-amino-5-phosphono-valerate (APV; 100 microM), and potentiated by 100 nM glycine. Few neurons responded to the receptor agonists kainate (100 microM), or quisqualate (1-10 microM). These observations suggest that glutamate induced depolarization of primary sensory neurons is mediated predominantly by NMDA receptors. PMID- 2905032 TI - Reimbursement for dental injury under workers compensation. PMID- 2905033 TI - Overexpression of either c-myc or c-erbB-2/neu proto-oncogenes in human breast carcinomas: correlation with poor prognosis. AB - Tumor specimens from 116 untreated patients with primary breast carcinoma at different clinical stages were analyzed for the structure and/or the expression of c-myc and c-erbB-2/neu proto-oncogenes. An amplification of the c-myc proto oncogene (3 to greater than 50 fold) was detected only in 6% of carcinomas, with no evidence of locus rearrangement. High c-myc RNA levels detected in 45% of tumors were found significantly (p less than 0.01) correlated with lymph node involvement. Amplification (3 to greater than 30 fold) of the c-erbB-2/neu gene was observed in 20% of cancers. A 5 kb c-erbB-2/neu gene transcript was detected in the 103 cancer specimens analyzed. High levels of transcripts were observed in 36% of tumors. Overexpression did not depend only on amplification since found in 14 tumor samples with a single gene copy. The gene amplification and overexpression were found significantly associated with cancers of poor prognosis. Moreover our data show that both proto-oncogenes are overexpressed only in 12.5% of tumor samples and suggest that each gene might play a different role in tumor progression. PMID- 2905034 TI - DNA restriction fragment length polymorphisms at either end of the c-raf-1 locus at 3p25. AB - We report the identification and characterization of two restriction fragment polymorphisms (RFLPs) associated with the human c-raf-1 protooncogene located on chromosome 3 (3p25). EcoRI digestion produces an RFLP derived from the 5'flanking sequences with a heterozygosity of 28%, and TaqI produces an RFLP representing the 3' flanking sequences with a heterozygosity of 25%. The finding of RFLPs associated with a potential oncogene may provide a method of analysis for determining genetic susceptibilities to certain cancers. PMID- 2905036 TI - [Social support, social network--health and disease]. PMID- 2905035 TI - Nutritional influences on adrenal chromaffin cell development: comparison with central neurons. AB - Neurotransmitter systems in the developing brain are generally protected from growth retardation associated with nutritional deprivation. To investigate if such protective mechanisms extend to similar tissues in the peripheral sympathetic system, maturation of the chromaffin cells of the adrenal medulla and development of their centrally derived splanchnic innervation were evaluated in rats whose nutritional status had been altered during the neonatal period by increasing (16-17 pups/litter) or decreasing (five to six pups/litter) the litter size from the standard (11-12 pups/litter). Ontogeny of adrenal catecholamine stores and activities of catecholamine-biosynthetic enzymes tyrosine hydroxylase and phenylethanolamine N-methyltransferase were monitored, along with activity of choline acetyltransferase, a marker enzyme for the preganglionic neurons innervating the chromaffin cells. Neonatal nutritional deprivation slowed body weight gain and retarded development of the chromaffin cells, as evidenced by subnormal catecholamine stores, tyrosine hydroxylase and phenylethanolamine N methyltransferase activities. The effects persisted despite the complete recovery of body weights postweaning. The developmental alterations were not caused by overcrowding stress, as plasma corticosterone levels were not elevated in the large litter group. Neonatal nutritional enrichment promoted body weight gain but failed to enhance development of adrenal catecholamines; tyrosine hydroxylase and phenylethanolamine N-methyltransferase activities were elevated only in the preweaning period. In contrast to effects on the chromaffin cells, altered neonatal nutritional status had only minor, transient effects on the development of the centrally derived cholinergic innervation of the adrenal and produced only small changes (less than 10%) in brain tyrosine hydroxylase activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2905037 TI - Impairment of yeast pre-mRNA splicing by potential secondary structure-forming sequences near the conserved branchpoint sequence. AB - The absolutely conserved TACTAAC box within introns of RNA polymerase II transcribed genes of the yeast Saccharomyces cerevisiae serves an indispensable role in lariat formation. We show in this report that rather short palindromic sequences inserted into the yeast actin gene intron immediately 3' to the TACTAAC box block the second but not the first splicing step. In contrast, a palindromic sequence inserted some 23 bp 3' of the TACTAAC box did not affect correct and efficient splicing. The data suggest that hairpin structures that might form adjacent to the branchsite sequence interfere with some necessary alteration of the spliceosome required for 3' intron cleavage and exon ligation. PMID- 2905038 TI - Isolation, characterization and evolutionary relatedness of three members from the soybean multigene family encoding chlorophyll a/b binding proteins. AB - The soybean light-harvesting complex II (LHC II) was composed of one major and three minor chlorophyll a/b (Cab) binding proteins. This study demonstrated that the soybean genome contained at least 11 genes that code for these Cab proteins. Three members of the soybean Cab gene family were characterized. Cab 3 coded for a 25.7 kD mature apoprotein with a 32 amino acid transit peptide. Comparisons with previously published Cab protein sequences indicated that Cab 3 coded for the major Cab protein of LHC II. Cab 2 coded for a novel Cab protein with an apparent molecular weight of 24.6 kD. Cab 2 retained a high degree of similarity with Cab 3, but distinguished itself from previously reported minor photosystem II type II Cab genes and products. Finally, Cab 1 was determined to be a pseudogene that had two deletions relative to Cab 2 and Cab 3. PMID- 2905039 TI - Differential premature termination of transcription as a proposed mechanism for the regulation of coronavirus gene expression. AB - We propose that the different subgenomic mRNA levels of coronaviruses are controlled through differential premature termination of transcription, and are modulated by the relative strength of transcriptional initiation/blockage events. We present the complete set of sequences covering the leader encoding and intergenic regions of the MHV-A59 strain. A computer-assisted analysis of the two now complete sets of these sequences of strain IBV-M42 and MHV-A59 shows that, in contrast to the previous theory, differences amongst stabilities of intermolecular base-pairings between the leader and the intergenic regions are not sufficient to determine the mRNA gradients in both MHV and IBV infected cells. Neither can the accessibility of the interacting regions on the leader and the negative stranded genome, as revealed by secondary structure analysis, explain the mRNA levels. The nested gene organisation itself, on the other hand, could be responsible for observed mRNA levels gradually increasing with gene order. Relatively slow new initiation events at intergenic regions are proposed to block elongation of passing transcripts which, via temporary pausing, can cause premature termination of transcription. This effects longer transcripts more than shorter ones. PMID- 2905040 TI - Isolation and mapping of a polymorphic DNA sequence (pEFD52.1) on chromosome 15. PMID- 2905041 TI - Isolation and mapping of a polymorphic DNA sequence (pTHH55) on chromosome. PMID- 2905042 TI - Isolation and mapping of a polymorphic DNA sequence (pEFZ33) on chromosome 15. PMID- 2905043 TI - Isolation and mapping of a polymorphic DNA sequence (pEFD64.1) on chromosome 3. PMID- 2905044 TI - DraI and ScaI RFLPs at human tyrosine hydroxylase (TH) gene locus. PMID- 2905045 TI - BclI RFLP at the DXS16 locus. PMID- 2905046 TI - Xba I polymorphisms in the 5' region of human erythrocyte alpha spectrin gene (Spna). PMID- 2905049 TI - 5'-flanking sequence of a glutamine synthetase gene specifying the beta subunit of the cytosolic enzyme from Phaseolus vulgaris L. PMID- 2905047 TI - Identification of two novel members of erbA superfamily by molecular cloning: the gene products of the two are highly related to each other. AB - Two v-erbA-related genes, named ear-2 and ear-3, have been identified in the human genome and characterized by cDNA cloning. These genes are predicted to encode proteins that are very similar in primary structure to receptors for steroid hormones or thyroid hormone (T3). In addition, amino acid sequences of the ear-2 and ear-3 gene products are very similar each other especially at the DNA binding domain (86% homology) and at the putative ligand binding domain (76% homology). Northern hybridization with ear DNA probes of RNAs from various tissues of a human fetus reveals that the expression of ear-2 is high in the liver whereas the expression of ear-3 is relatively ubiquitous. Hybridization analysis of DNAs from sorted chromosomes shows that the ear-2 gene is located on chromosome 19 and ear-3 on chromosome 5, indicating that the two genes are clearly different from each other. PMID- 2905048 TI - A large deletion encompassing the entire alpha-like globin gene cluster in a family of northern European extraction. AB - We describe a new deletional form of alpha thalassemia segregating in three generations of a family of northern European origin. A full-term female girl had hypochromic, microcytic anemia since early infancy associated with delayed language development, slow growth and weight gain. Hematologic studies suggested the presence of alpha thalassemia. Gene-blotting studies showed no abnormal alpha like globin gene fragments; however, studies of inheritance of informative polymorphic restriction fragments using zeta, alpha and 3'-alpha-hypervariable region (3'-HVR) probes showed evidence for an extensive deletion encompassing the entire alpha-like globin gene cluster. The 3' breakpoint of this deletion maps beyond the 3'-HVR, a region implicated as a hot spot for the generation of other large deletional events within the alpha-like cluster. The 5' breakpoint maps at least 10 kilobases (kb) 5' to the zeta-globin gene. The minimum size estimate for this deletion is greater than 47 kilobases. PMID- 2905050 TI - A human minisatellite probe reveals RFLPs among individuals of two angiosperms. PMID- 2905051 TI - A BglI polymorphism in the type VI (alpha 3) procollagen gene [COL6A3]. PMID- 2905052 TI - A TaqI polymorphism at human homeo box gene locus on chromosome 12. PMID- 2905053 TI - A TaqI RFLP for the human fibronectin (FN1) gene. PMID- 2905054 TI - TaqI RFLP identified by probe VK17A (DXS294) at Xq26. PMID- 2905055 TI - Isolation and mapping of a polymorphic DNA sequence (cTB14.16) on chromosome 10 [D10S33]. PMID- 2905056 TI - Isolation and mapping of a polymorphic DNA sequence (cTB14.15) on chromosome 10 [D10S32]. PMID- 2905057 TI - Isolation and mapping of a polymorphic DNA sequence (cTBQ12) on chromosome 10 [D10S29]. PMID- 2905058 TI - Administering and monitoring epidural analgesia. The use of newer epidural narcotics: fentanyl and sufentanyl. PMID- 2905059 TI - Prenatal diagnosis of cystic fibrosis using linked DNA probes. AB - This paper presents data collected in Europe on 107 prenatal diagnoses of cystic fibrosis (CF) using linked DNA markers. To date, 38 children have been born without CF, as predicted, demonstrating the present rapid move from research to clinical genetic service. PMID- 2905060 TI - [Fatal septicemia caused by intra-uterine device in aplasia of acute leukemia]. PMID- 2905061 TI - Inhibition of gastric acid secretion by peptide YY is independent of gastric somatostatin release in the rat. AB - The purpose of this study was to determine whether the inhibitory action of peptide YY (PYY) on gastric acid secretion is attributable to the release of gastric somatostatin in rats. Two groups of rats (six rats/group) were anesthetized with urethane and prepared with gastric fistulas and jugular catheters. Pentagastrin (18 micrograms/kg-h) was given intravenously for 150 min to stimulate gastric acid secretion. Intravenous PYY (130 micrograms/kg-h) inhibited pentagastrin-stimulated gastric acid secretion significantly (P less than 0.05). Administration of iv PYY resulted in a 41% reduction (P less than 0.05) in pentagastrin-stimulated gastric acid secretion. In another group of anesthetized rats, administration of PYY (10(-7), 10(-8) M) failed to stimulate a release of somatostatin from the isolated-perfused rat stomach. Our findings indicate that PYY can inhibit gastric acid secretion independently of release of gastric somatostatin in the rat. PMID- 2905062 TI - Inhibition of growth hormone-stimulated lipolysis by somatostatin, insulin, and insulin-like growth factors (somatomedins) in vitro. AB - The effects of somatostatin, insulin, insulin-like growth factor I (IGF-I), and insulin-like growth factor II (IGF-II)/MSA on growth hormone (GH) (1 microgram/ml)-induced lipolysis were examined employing chicken adipose tissue in vitro. Basal and GH-stimulated glycerol release were inhibited by somatostatin (1 ng/ml) and by IGF-II/MSA (10 and 100 ng/ml). Insulin and IGF-I (10 and 100 ng/ml) completely inhibited the lipolytic response to GH without affecting basal glycerol release. Insulin and IGF-I were equipotent in inhibiting GH-induced lipolysis while IGF-II is only 16% as potent as insulin. PMID- 2905063 TI - Differential effects of anxiolytics and beta-receptor blocking drugs on novelty oriented ("neophobic") behavior in the rat. AB - The effects of diazepam, I-propranolol and isamoltane (CGP 361 A) (I isopropylamino-3[2-(I-pyrrolyl)-phenoxy]-2-propranol), a drug with beta-receptor blocking and anxiolytic-like properties, on behavioral responses in rats encountering either a novel object or a drinking bottle in an unfamiliar open field ("neophobic" behavior) were evaluated. Diazepam (1-5 mg/kg p.o.) and isamoltane (0.5-1.0 mg/kg p.o.) showed a similar pattern of effects in both test paradigms used. They counteracted the fear-induced suppression of behavioral responses in the presence of novelty: they shortened the approach latencies, increased the exploration-oriented activities and reduced grooming. Propranolol, however, in comparison with isamoltane (1.0 and 2.5 mg/kg i.p.) at equivalent doses, failed to significantly change any of the parameters measured in either of the two test situations. The results therefore indicate that neophobic behavioral responses discriminate between central anxiolytic and peripheral beta-blocking actions of drugs and further validate neophobic behavior as an animal model of anxiety. PMID- 2905064 TI - Suspension of neuroleptic therapy in acute schizophrenia. AB - What are the effects of the abrupt discontinuation of neuroleptics (suspension therapy) in acutely schizophrenic patients with unsatisfactory remission under standard neuroleptic therapy? This question was investigated in a prospective study of 159 patients. In addition to the psychopathologic results of the AMDP system, the self rating (VAMS) and nurses' rating (NGI) of psychopathologic parameters were assessed. Indication for suspension of the neuroleptic treatment was established in 21 patients (13%) following definite criteria. Suspension therapy brings about a rapid improvement in psychopathologic results. The paranoid-hallucinatory syndrome also undergoes remission; this is to be understood as an immediate effect of suspension of therapy. In one-third of the cases complete suspension effects, in another third partial suspension effects, and in the remaining third failure occur. Further advantages of suspension therapy are the reduction in neuroleptic drug requirements and a favorable influence on the entire treatment course. The investigation does not permit any statement as regards prediction of the suspension effect or concerning the mechanism underlying the suspension therapy. PMID- 2905065 TI - [Tardive dystonia--a case report on therapy and metaphylaxis]. AB - The article deals with a case of tardive dystonia describing grave complications as result of long-term recidive-fluphenacindepot-treatment; therapy and metaphylaxy-problematic are being discussed as well. PMID- 2905066 TI - Family screening in medullary thyroid carcinoma presenting without a family history. AB - Systematic screening of the families of a series of 39 patients with apparently sporadic medullary thyroid carcinoma detected seven new cases in four families. A negative family history in a patient presenting with medullary thyroid carcinoma is not reliable in excluding familial disease, and family screening should be considered for new patients with medullary thyroid carcinoma. PMID- 2905067 TI - [Secondary prevention of coronary disease using drugs]. PMID- 2905068 TI - [Astemizole in the treatment of acute rhinopharyngitis (common cold). A double blind study in pediatrics]. PMID- 2905069 TI - Altitude insomnia: studies during an expedition to the Himalayas. AB - During an expedition to the Himalayas, we studied the sleep and respiration of six climbers. Three ingested acetazolamide (500 mg) daily throughout the climb and the other three ingested placebo. At high altitude (4,150-4,846 m), each subject ingested temazepam (10 mg) for one night and placebo for another. Acetazolamide improved sleep above 2,750 m, but it is uncertain whether this was due to sedation or to improvements in arterial oxygen saturation. Sleep was markedly disturbed in all subjects above 4,000 m. Temazepam improved sleep, and in subjects taking acetazolamide, it reduced sleep-onset latencies and increased sleep efficiency close to that of sea level values. These observations suggest that the prophylactic use of acetazolamide is likely to improve sleep in climbers and that a low dose of a benzodiazepine such as temazepam (10 mg) may be beneficial at high altitude. Studies are now needed to exclude any possibility of respiratory impairment at altitude before a firm recommendation can be made regarding the routine use of this hypnotic. PMID- 2905070 TI - [AIDS Stockholm, 6 nurses]. PMID- 2905071 TI - [Gastroduodenal ulcers]. PMID- 2905072 TI - [Inhibition of cytochrome P-450 and cytochrome b5 induced by Clostridium perfringens alpha toxin]. PMID- 2905073 TI - The anatomy of gubernaculum testis and processus vaginalis in cryptorchidism. AB - The macroscopic anatomy of gubernaculum testis and processus vaginalis has been carefully studied during 150 consecutive orchiopexies. In subcutaneous and canalicular testes a well defined gubernaculum was found representing a morphologic continuity from the testis to the bottom of the scrotum. The gubernaculum was detectable in only one of four abdominal testicles. In 75% of the patients the serous communication between the testis and the abdominal cavity was lost. 43% of the patients still had a detectable rest of the processus vaginalis of which one third presented with a clinical hernia. PMID- 2905074 TI - Histological studies of gubernaculum testis taken during orchiopexies. AB - Twenty-five gubernacula were removed for histological examination. All were routinely stained and some were additionally stained for elastic fibres and content of hyaluronic acid. The gubernaculum consisted of moderately vascular, fibrofatty tissue with a core of essentially longitudinally oriented collagenous fibres surrounded by mature fatty tissue. No contractile elements were seen in the gubernaculum. It did not differ from subcutaneous fascia concerning content of elastic fibres and hyaluronic acid. PMID- 2905075 TI - The role of commercial sources in the adoption of a new drug. AB - The goal of this study was to focus on the adoption process for a specific new drug upon its introduction to the marketplace. The reception of temazepam by doctors was investigated in interviews with 124 specialists and general practitioners. Their response to this new drug at different stages of the adoption process was related to contact with drug information sources and to characteristics of the doctor and practice. Within about 13 months after its release, 71% were familiar with temazepam, 48% had prescribed it, and 27% now preferred it to the alternatives. Contact with the detailman regarding this drug was the most consistent predictor of favourable reception. Results suggest that the adoption of the new drug was related to commercial forces rather than to a doctor's professional involvements. PMID- 2905076 TI - [A case of late diagnosis of analgesic nephropathy]. PMID- 2905077 TI - [A case of aortoarteritis simulating Bechterew's disease]. PMID- 2905078 TI - [Blood lipids and the indicators of lipid peroxidation in patients with hemorrhagic fever with nephrotic syndrome]. AB - Lipid peroxidation (LPO) was studied in 66 patients suffering from hemorrhagic fever with the renal syndrome (HFRS) by the results of determination of the content of malonic dialdehyde and acyl hydroperoxides in plasma. LPO intensity rose considerably, being the highest in a severe course of disease. LPO disorder developed against a background of considerable shifts in the level of total blood lipids and their fractions: cholesterol, total beta- and pre-beta-lipoproteins, total phospholipids and triglycerides. The author discussed the importance of LPO disorders revealed in HFRS pathogenesis and determination of the severity of disease and its prognosis. PMID- 2905079 TI - Effect of duration of exposure to benzo(a)pyrene diol-epoxide on neoplastic transformation, mutagenesis, cytotoxicity, and total covalent binding to DNA of rodent cells. AB - We examined the effect of different durations of exposure (20 sec to 24 hr) to (+/-) 7-beta,8 alpha-dihydroxy-9 alpha, 10 alpha -epoxy-7,8,9,10 tetrahydrobenzo(a)pyrene (BPDE I) on the induction of transformation in C3H/10T 1/2 cells and of mutations to 6-thioguanine resistance in Chinese hamster ovary cells (CHO), as well as on BPDE I-DNA binding in these two cell lines. A 20-sec exposure of the cells to BPDE I was sufficient to induce mutations and morphological transformation in vitro. However, the transformation frequency in CH3 mouse-embryo-derived 10T 1/2 cells increased twofold and the frequency of mutations in CHO cells sixfold when the exposure time to BPDE I was increased from 20 sec to 8 h. Cytotoxicity increased under similar conditions. A large number of BPDE I-DNA adducts were formed in both cell lines within the first 15 min of exposure of the cells to this ultimate carcinogen. The total covalent binding did not increase with longer than 15-min incubation times. These results suggest that in addition to its covalent binding to DNA, BPDE I may influence other cellular mechanism(s) that are responsible for the initiation of transformation and mutagenesis. PMID- 2905080 TI - Quantitative risk assessment: qualms and questions. AB - Within the past ten years, quantitative risk assessment has come to play a central role in the federal regulation of carcinogens. Federal agencies use quantitative risk both to set priorities and to establish exposure levels. The use of quantitative risk assessment is mandated by Executive Orders requiring performance of cost-benefit analysis, although performance of assessments has often been ascribed to the Supreme Court decision in the 1980 "benzene" case. Quantitative risk assessment is a deeply flawed methodology with results that give a false sense of certainty and objectivity. Also, the nature of quantitative risk assessment methodologies currently in use makes it difficult for members of the public to scrutinize and assess regulatory actions. Quantitative risk assessment should not be used for regulation of carcinogens, especially not for establishing exposure levels. Instead, alternative methodologies should be utilized, which are appropriately reflective of uncertainty and which are more readily accessible to public scrutiny and participation. PMID- 2905081 TI - Comparison of behaviors for detection of heritable mutations. AB - Groups of five male HA (ICR) mice were injected intraperitoneally with 60, 150, 300, or 600 mg/kg body weight of ethyl methanesulfonate (EMS) or with saline vehicle. Each male was mated to two untreated females at 2 and 5 weeks after treatment. The two successive matings utilized sperm derived from post- and pre meiotic germ cells, respectively. Progeny were evaluated for litter size, body weight, negative geotactic response, swimming patterns, limb use while swimming, water escape time, and open-field motor coordination activity. Body weight, geotactic response, limb use, and open-field behavior test results demonstrated that EMS causes heritable behavior mutations in both post- and pre-meiotic germ cells. Among the tests that showed inherited differences between control and treated groups, the computer-monitored open-field behavior test was the most definitive. PMID- 2905082 TI - Effect of heat shock on the mutagenicity of mutagens and carcinogens in Euglena gracilis. AB - The effect of heat-shock treatment (42 degrees C for 15 min) on the ability of four mutagens and carcinogens to induce hereditary bleaching in Euglena gracilis cells was investigated. All four mutagens (treatment time: 1-24 h) tested after heat shock increased the frequency of bleached mutants of Euglena gracilis. PMID- 2905083 TI - Induction of sister chromatid exchanges by ergot compounds in Chinese hamster ovary cells in vitro. AB - Five ergot alkaloids, d-lysergic acid derivatives, were tested for the induction of sister chromatid exchange (SCE) frequencies in cultured Chinese hamster ovary cells. The concentrations of the test substances ranged between 10(-5) and 10(-8) M. Ergotamine, ergonovine, and methylergonovine induced a significantly high number of SCEs at all the concentrations used, while with ergocristine this occurred only at the highest concentration. alpha-Ergocryptine failed to induce SCEs at any concentration. It is therefore surmised that ergotamine, ergonovine, and methylergonovine are effective inducers, ergocristine is a weak inducer, and alpha-ergocryptine is a noninducer in Chinese hamster ovary cells in vitro. PMID- 2905084 TI - [The polyposis project]. PMID- 2905085 TI - [Retrospective diagnosis of epidemic nephropathy]. PMID- 2905086 TI - In vivo suppression of stearyl CoA desaturase activity by griseofulvin: evidence against the involvement of lipid peroxidation. AB - Administration of a diet containing 2.5% (w/w) griseofulvin (GF) resulted in a significant decrease in hepatic microsomal stearyl CoA desaturase activity compared to desaturase activity in microsomes from animals fed a normal rat chow diet. Desaturase activities were 0.66 +/- 0.18 vs 0.16 +/- 0.09 nmoles oleyl CoA formed/min/mg protein for control and GF-fed animals, respectively. Examination of lipid peroxides in microsomes from control and GF-treated rats showed an approximate fivefold higher concentration of lipid peroxides in microsomes from GF-treated rats compared to that from controls. However, when rats were fed a diet containing GF and diphenyl-p-phenylenediamine an inhibitor of lipid peroxidation, stearyl CoA desaturase activity was still similar to that observed with GF alone, even though microsomal lipid peroxides were reduced to nondetectable levels. In vitro stimulation of microsomal lipid peroxidation using ADP-Fe and EDTA-Fe did not result in a significant decrease in desaturase activity. Results of our experiments show that dietary administration of GF results in a marked decrease in stearyl CoA desaturase activity in hepatic microsomes. Although GF feeding stimulates microsomal lipid peroxidation, increase in microsomal peroxidation does not appear to be the mechanism by which GF feeding decreases desaturase activity. GF appears to act by decreasing the terminal desaturase activity. PMID- 2905087 TI - Recovery of human fetal pancreas after one year of implantation in the diabetic patient. AB - Between one and six cultured human fetal pancreata were allografted into five insulin-dependent diabetic recipients and their progress monitored for a year on each occasion. To prevent rejection the tissue was cultured for 1-3 weeks before transplantation, the HLA-DR antigens of the donor tissue were matched with those of the recipient when a single pancreas was used, and four of the recipients were immunosuppressed, three because of coexisting renal grafts. Graft function was observed transiently in one of the recipients. In three others human fetal pancreas was recovered 9-14 months after transplantation, although it was being slowly rejected during this time. Beta cells were present in the graft but did not function adequately to enable immunoreactive C-peptide to be measured in peripheral blood. The issues of rejection and immaturity of the human fetal pancreas will need to be surmounted if the potential of the human fetal pancreas to normalize blood glucose levels in diabetic man is ever to be realized. PMID- 2905088 TI - Adoptive immunity in immune-deficient scid/scid mice. I. Differential requirements of naive and primed lymphocytes for CD4+ T cells during rejection of minor histocompatibility antigen-disparate skin grafts. AB - Using a model system in which mature lymphocytes were adoptively transferred into immunodeficient C.B17-scid/scid recipients, the requirement for CD4+ T cells in rejection of previously healed-in multiple minor-H-antigen-disparate skin grafts was investigated. Depletion of functional CD4+ cells was accomplished by anti-CD4 antibody + complement treatment prior to adoptive transfer followed by chronic anti-CD4 serotherapy in vivo. Homozygous scid mice harboring nondepleted naive donor cells effectively rejected minor-H-antigen-disparate grafts, whereas scid/scid mice harboring CD4+ T-cell-depleted naive cells did not. Homozygous scid mice harboring minor-H-antigen-primed cells rejected the minor-H-antigen disparate allografts regardless of whether or not the animals had received anti CD4 treatment, although rejection by the mice receiving anti-CD4 treatment was retarded compared to mice not receiving anti-CD4 treatment. All the mice that received viable donor cells rejected minor + H-2 disparate allografts, demonstrating effective immunity in this case was not dependent upon the activity of CD4+ T cells. These data suggest that in responses against multiple minor-H antigen-disparate tissue, primary allograft rejection is absolutely dependent upon CD4+ cells, and secondary allograft rejection is not. The implications of these findings in understanding interactions of T cell subsets in vivo and of the utility of using homozygous scid mice as recipients for exploring the function of transferred lymphoid cell populations are discussed. PMID- 2905089 TI - [Acute renal insufficiency due to intentional glafenine poisoning]. PMID- 2905090 TI - [Almitrine bismesylate. A peripheral chemoreceptor agonist]. PMID- 2905091 TI - [Ambulatory orchiopexy in children]. PMID- 2905092 TI - The relationship between the pharmacokinetics and pharmacodynamics of spinal opioids. Minireview based on a doctoral thesis. AB - Spinal opioids have been used clinically since the late seventies to treat acute, traumatic, obstetric and chronic pain. In this article the influence of the pharmacokinetics on the dynamics of intrathecal and epidural opioid administration are discussed with reference to current knowledge. PMID- 2905093 TI - [Individualization of the surgical treatment of cryptorchism]. PMID- 2905094 TI - [Pediatric surgical one-day hospital]. AB - 670 sick children were operated upon under conditions of a one-day surgical hospital. Selection of the patients and preoperative preparing was fulfilled at the polyclinic. The selected children had the following diseases: inguinal (119) and umbilical (87) hernias, hernias of the linea alba (14), hydrocele (68), cryptorchidism (81), benign tumours of soft tissues (43), phimosis (258). Complications in the nearest postoperative period made up 0.3%. The economic effect of the treatment of 670 children with surgical diseases at the surgical one-day hospital was more than 50,000 rubles. PMID- 2905095 TI - [Tranquilizers in the combined treatment of patients with arterial hypertension]. PMID- 2905096 TI - [Prevention of stress ulcer and nosocomial pneumonia]. PMID- 2905097 TI - [Endoscopic removal of bile duct calculi (papillotomy, mechanical lithotripsy, laser-induced lithotripsy]. PMID- 2905098 TI - [New developments and trends in the drug therapy of chronic inflammatory bowel diseases]. PMID- 2905099 TI - [Therapy of chronic inflammatory bowel diseases. Clinical aspects and therapy of drug-induced side effects]. PMID- 2905100 TI - [Structural and functional changes in the brain caused by aging]. PMID- 2905101 TI - [Therapy of peptic ulcer. H2 receptor blockers]. PMID- 2905102 TI - [Inflammatory mediators in the pathogenesis of obstructive bronchial diseases: consequences for therapy]. PMID- 2905103 TI - [The significance of chronopharmacology for drug therapy]. PMID- 2905104 TI - Monocyte-macrophages increase in the bursal follicular medulla following bacterial intracloacal inoculation of Bordetella pertussis in chicks. PMID- 2905105 TI - [Brain tyrosine hydroxylase activity in behavior-selected silver foxes]. AB - In two groups of silver foxes--i.e. selected by the domestic type of behaviour and aggressive ones--studies have been made on the activity of the key enzyme in biosynthesis of catecholamines--i.e. tyrosine hydroxylase from the brain. Domesticated animals exhibited higher enzymic activity in the locus coeruleus, hypothalamus and cortex. Animals from both groups did not differ with respect to the level of tyrosine hydroxylase activity in the corpus striatum. The enzymic reactions of homogenates from locus coeruleus region of the brain in both groups of animals, as well as homogenates from the corpus striatum of the brain of aggressive animals exhibited low and approximately equal values of Michaelis constant for tyrosine. The value of KM was 3 times higher in the hypothalamus in both groups of foxes and in the corpus striatum of tame animals. Presumably, selection of silver foxes for the domestic type of behaviour resulted in the increase of biosynthesis of catecholamines in the brain due to the increase in the number of enzyme molecules. The increase in the activity of tyrosine hydroxylase in noradrenaline system of the brain may be associated with changes in the behavioural pattern of animals resulting from selection. PMID- 2905106 TI - Drugs recently released in Belgium. Recombinant DNA tissue plasminogen activator (rt-PA) famotidine-sultamicillin. PMID- 2905107 TI - Gastric cytoprotection induced by prostaglandin-dopaminergic mechanism. AB - The cytoprotective effects on the gastric mucosa of the Bromocriptine, a peripheral dopaminergic receptor agonist compared with Misoprostol against ethanol-induced injury were studied. Pretreatment with SCH 23390 (a DA1 receptor antagonist) and Domperidone (a DA2 receptor antagonist), showed that Misoprostol was peripheral dopaminergic receptor dependent in the gastric cytoprotective mechanism, and that Bromocriptine was a selective peripheral DA2 receptor agonist in the gastric cytoprotection mechanism; as well as, indomethacin pretreatment, showed that peripheral DA2 receptors were endogenous prostaglandin dependent. In conclusion, a prostaglandin-dopaminergic mechanism was postulated in gastric cytoprotection. PMID- 2905108 TI - The natural history of liver disease in alpha 1-antitrypsin deficient children. AB - During 1972-1974, 200,000 Swedish infants were screened for alpha 1-antitrypsin deficiency. Of 127 PiZ (Protease inhibitor) children followed from infancy to 12 years of age, four PiZ children with neonatal liver disease have died; two of liver cirrhosis, one was found to have liver cirrhosis at autopsy, having died of aplastic anemia and the fourth died in an accident. Liver microscopy showed a mild increase of periportal fibrous tissue. Another PiZ child died of anaphylactic shock. At 12 years of age, none of the PiZ children have clinical symptoms of liver disease. No PiZ-, PiSZ, PiS- or PiFZ child has had any clinical symptom of liver disease. One PiSZ child died of sudden infant death syndrome. Laboratory analyses from birth through 12 years of age have shown increased S Bilirubin levels in 11% of the PiZ infants, which normalized within the first half year of life. S-GT was abnormal in about half of the infants, but had normalized when checked at 8 and 12 years of age in all but 6-3% of the PiZ children. The percentage of abnormal S-ALAT test results have decreased from 73% during the first year of life, to about 15% at the age of 12. The range of the abnormal levels also decreased considerably. Abnormal S-GT or S-ALAT levels were found in about 20% of the PiSZ infants, the proportion decreasing to 2% at the age of 12. PMID- 2905109 TI - [Assessment of the clinical activity of fluoxetin (Prozac) according of the "Stars of Liege" model]. AB - Ten psychiatrists have independently rated the clinical profile of fluoxetin (Prozac) at the daily dose of 20 mg according to a "Stars of Liege" model comprising three parameters of therapeutic activity (antidepressant, psychostimulant and anxiolytic) and three parameters of side-effects (anticholinergic, sedative and hypotensive). Each parameter, graduated from 0 to 5 (no, very weak, weak, moderate, potent, very potent effect) was rated by each investigator according to his personal experience with at least 10 patients. Mean ratings given to fluoxetine show a moderate antidepressant effect, equal to amitriptyline (Redomex, Tryptizol 75 mg/d, clomipramine (Anafranil 75 mg/d and nialamide (Niamide 100 mg/d, weak psychostimulating and anxiolytic effects, a very weak sedative effect and a lack of anticholinergic and hypotensive effects. Digestive side-effects of moderate intensity were also noted as well as a very weak anorexia. The important variability between investigators in the rating of the clinical profile of fluoxetine suggests that more experience is needed in order to define better its physiognomy. PMID- 2905110 TI - [Stimulation of somatotropin hormone by piribedil, a dopaminergic agonist, in endogenous depression. Preliminary study]. AB - Piribedil, a dopaminergic agonist, was administered intravenously (0.5 mg over 10 minutes) to two unipolar endogenous depressed. The two patients, a 38-year-old man and a 60-year-old woman, were matched for age and sex with two volunteers without any mental illness. Effects of piribedil on plasma levels of growth hormone and on blood pressure were studied. The two volunteers evaluated their "feelings" of anxiety and of physical comfort using visual analogue scales. The experimentation was repeated in a double blind fashion with a placebo. Piribedil induced an elevation of GH in the normal man but not in the depressed man. In contrast, no increase was noted in women. No elevation of GH was observed after placebo. Importance of factors such as depression, sexual steroid environment and influence of stress are discussed. PMID- 2905111 TI - Anaesthesia for reconstructive urethral surgery. PMID- 2905112 TI - Management of alcohol withdrawal: treatment controversies. PMID- 2905113 TI - Duration of the inhibitory activity on histamine-induced skin weals of sedative and non-sedative antihistamines. AB - The inhibitory effect of orally administered dexchlorfeniramine (4 mg/day), cyproheptadine (8 mg/day), astemizole (20 mg/day), loratadine (40 mg/day) and terfenadine (120 mg/day) on the size of histamine-induced weals was tested by skin prick test with histamine in an open study including 23 healthy individuals. The antihistamines were administered for 2 days in the nationally recommended therapeutic doses. For all drugs the maximal weal suppression with the dosage chosen was recorded the day after the last dosage, being 29% (for dexchlorfeniramine), 72% (for cyproheptadine), 50% (for astemizole), 62% (for loratadine), and 56% (for terfenadine) of the baseline value. For the drugs in the same order the duration of the inhibitory effect of the drugs after the last dose administered was between 3-4, 7-11, 17-28, 4-7, and 4-7 days, respectively. PMID- 2905114 TI - Fine structure of boundary tissue of the seminiferous tubules in the scrotal and abdominal testes of naturally unilateral cryptorchid West African dwarf goats. AB - The boundary tissue of the seminiferous tubules in the scrotal and abdominal testes of naturally unilateral cryptorchid West African dwarf goats comprised an inner non-cellular, a middle cellular and peripheral cellular lamellae. In the scrotal testes, these components were compact and their arrangement conformed to that described for other domestic ruminants except that here, the basal lamina associated with the seminiferous epithelium was homogeneous and in tact. Alterations due to cryptorchidism as observed in the contralateral abdominal testes include general loss of compactness due to depletion and disorganization of structural extracellular materials like basal lamina coat of myoid cells and collagen fibrils, the splitting of the basal lamina of the seminiferous epithelium into 8-12 thin layers, poor differentiation of the myoid cells and the accumulation of lipid droplets within their cytoplasm. It is concluded that the normal caprine boundary tissue conforms entirely to the characteristics of 'Type C' category in the existing classification. The ultrastructural alterations due to abdominal retention of the testis resemble the testicular changes ascribed to the disturbance of pituitary-testicular hormonal axis. PMID- 2905115 TI - Identification of genetic variation in the bovine major histocompatibility complex DR beta-like genes using sequenced bovine genomic probes. AB - Two bovine genomic clones that crosshybridize with HLA-DR beta cDNA have been isolated. Nucleotide sequence analysis of the beta 1, beta 2 and transmembrane (TM) exon regions for one of these clones revealed 70, 89 and 86% identity with the corresponding HLA-DR beta exons. Stop codons are present in the beta 1 and TM exons and a single base deletion toward the 3' end of the TM exon negates the consensus sequence for exon/intron splicing. Therefore, we conclude this is a bovine DR beta-like pseudogene, BoDR beta I. Exon-containing regions have been used as probes in Southern blot analyses of bovine genomic DNA digested with EcoRI. The beta 2 exon of BoDR beta I results in prominent bands of 18.9, 7.8, 7.2, 6.4, 5.6, 3.6, 3.0 and 2.7 kb. Polymorphisms were observed for all but the 18.9 kb band and at least three of these bands were identified in each of the 185 animals sampled. A probe containing the TM exon of BoDR beta I hybridizes only to the 5.6- and 3.6-kb bands, suggesting that these are allelic bands corresponding to this pseudogene. Results from hybridizations of a TM exon-containing probe of the second bovine DR beta-like clone (BoDR beta II) suggest that the 6.4- and 2.7 kb bands correspond to this second bovine gene. A nonpolymorphic 8.1-kb band results from a probe containing the BoDR beta I beta 1 exon. Major differences in frequency for the 6.4/2.7 alleles were found for the four breeds sampled. PMID- 2905116 TI - Close association between DNA polymorphism of bovine major histocompatibility complex class I genes and serological BoLA-A specificities. AB - Class I genes of the bovine major histocompatibility complex (MHC) were investigated by Southern blot hybridization and by serological analysis. A large number of class I restriction fragments and an extensive polymorphism were revealed when genomic DNA samples, digested with the restriction enzyme PvuII, were hybridized with a human cDNA probe. The result indicated the presence of multiple class I genes in cattle. The extensive restriction fragment length polymorphism (RFLP) was interpreted genetically by analysing five paternal half sib families comprising, besides the bulls, 50 offspring and their dams. No less than 21 RFLP types were distinguished in this limited sample. The class I polymorphism was also analysed using a serological test with sera corresponding to four workshop specificities (w2, w6, w10 and w16) and three locally defined specificities (SRB1, SRB2 and SRB3). There was an excellent agreement between the two typing methods since no RFLP type was associated with more than one specificity and five of the seven specificities were associated with a single RFLP type. Evidence for close genetic linkage between class I and DQ class II genes was obtained since no recombinant was found among 45 informative offspring. Linkage disequilibrium among class I, DQ class II and C4 genes was also observed. The blood group specificity M' was completely associated with the w16 class I specificity and with the haplotype I1DQ1BC4(2) in this material. PMID- 2905117 TI - Narcolepsy and HLA in the Japanese. AB - Narcolepsy is characterized by excessive daytime sleepiness and cataplexy. It had been reported that 100% of Japanese and Caucasian narcoleptic patients are HLA DR2 and HLA-DQw1 positive; last year, however, exceptionally rare cases of DR2 negative narcolepsy were reported. Conversely, we tested 190 Japanese narcoleptic patients, and all were still DR2 and DQw1 positive. Among several symptoms in narcoleptic patients, HLA-DR2 showed the strongest association with cataplexy. Exclusive association has been demonstrated between narcolepsy and a specific band of EcoRI-digested DQ beta fragments. In this paper Taq I-digested genomic DNAs were hybridized with a DQ alpha probe, and five specific bands were observed to associate strongly with particular HLA-DR or D specificities. Interestingly, the 6.0-kb band was found in 100% of 28 narcoleptic patients and in 54% of DR2 positive normal control subjects. For the time being, HLA-Dw2 is the better marker of the HLA-associating narcoleptic gene than is DR2, DQw1, 2.4-kb band of EcoRI-digested DQ beta, and 6.0-kb band of Taq I digested DQ alpha, because the frequency of DW2 is the lowest in normal control subjects. PMID- 2905118 TI - Associations of the autoimmune myasthenias with genetic markers in the immunoglobulin heavy chain region. PMID- 2905119 TI - Determination of RFLPs linked to multiple sclerosis susceptibility. PMID- 2905120 TI - Molecular genotypes of the T-cell receptor beta chain in families with multiple sclerosis. PMID- 2905121 TI - Immunohistochemical analysis of suppressor-inducer and helper-inducer T cells in multiple sclerosis brain tissue. PMID- 2905122 TI - Loss of functional suppression is linked to decreases in circulating suppressor inducer (CD4+ 2H4+) T cells in multiple sclerosis. PMID- 2905123 TI - Recognition of intracellular measles virus antigens by HLA class II restricted measles virus-specific cytotoxic T lymphocytes. PMID- 2905124 TI - Immunoregulation in rapidly progressive multiple sclerosis. PMID- 2905125 TI - Anti-CD4 and anti-CD2 monoclonal antibody infusions in subjects with multiple sclerosis. Immunosuppressive effects and human antimouse responses. PMID- 2905126 TI - Relationships between the calmodulin-dependent adenylate cyclases produced by Bacillus anthracis and Bordetella pertussis. AB - The nucleotide sequences for the calmodulin-dependent adenylate cyclases produced by Bordetella pertussis and Bacillus anthracis have recently been determined. The GC% for the B. pertussis and B. anthracis cyclase genes are about 65% and 29%, respectively. Despite this difference in nucleotide composition, these cyclases possess three highly conserved amino acid domains and share some nucleotide sequence homology. One of these conserved domains appears to be involved in ATP binding and is related to the consensus amino acid sequences present in many eukaryotic and prokaryotic ATP and GTP binding proteins. The possible relationship between these cyclases and eukaryotic calmodulin-dependent adenylate cyclases is discussed. PMID- 2905127 TI - Induction of gamma-glutamyl transpeptidase activity by all-trans retinoic acid in cultured rat liver epithelial cells. AB - The induction of activity of gamma-glutamyl transpeptidase (GGT) by all-trans retinoic acid in a chemically transformed rat liver epithelial cell line has been investigated. Retinoic acid increased the level of the GGT mRNA and this enhancement was progressive, depending on the duration of exposure and on the concentration of retinoic acid in the culture medium. When retinoic acid was removed from cultures which had been exposed to it for 4 days, the induced GGT activity remained unchanged. In contrast to transformed cell lines, retinoic acid did not induce the activity of GGT in normal/non-transformed rat liver epithelial cells. PMID- 2905128 TI - Molecular cloning of a cDNA coding for 70 kilodalton subunit of soluble guanylate cyclase from rat lung. AB - A complementary DNA clone corresponding to the 70 kDa subunit of soluble guanylate cyclase (EC 4.6.1.2) of rat lung has been isolated. The primary structure of the cDNA consisted of 3063 nucleotides including a 1857-nucleotide coding region for 619 amino acids, and the calculated molecular weight was 70476. Blot hybridization of total poly(A)+RNAs from rat tissues detected a mRNA of about 3.4 kilobases. The amount of mRNA was abundant in lung, cerebrum and cerebellum, moderate in heart and kidney, and low in liver and muscle. Southern blot analysis of high molecular weight genomic DNA from rat liver indicated the presence of one gene in the rat haploid genome. The amino acid sequence of the 70 kDa subunit has partial homology with particulate guanylate cyclase from sea urchin sperm, and protein phosphatase inhibitor I. PMID- 2905129 TI - Characterization of rat and human tyrosine hydroxylase genes: functional expression of both promoters in neuronal and non-neuronal cell types. AB - We describe the structure of the promoter and intron 1 of the human and rat tyrosine hydroxylase genes. The 5' flanking region of the two genes are 74% identical (+1 to -380) and contain a completely conserved cAMP response element. Although both genes are single copy, multiple splicing events of the human transcript lead to multiple mRNAs. Based on several lines of evidence alternative forms of mRNA of rat TH analogous to those in the human are not present. Both rat and human promoters direct the transcription of reporter genes when introduced into rat pheochromocytoma and fibroblast cells. PMID- 2905130 TI - Antimicrobial properties of methdilazine and its synergism with antibiotics and some chemotherapeutic agents. AB - The antihistamine methdilazine (Md) was found to possess a significantly high antibacterial action when tested against 367 strains of bacteria belonging to both Gram-positive and Gram-negative genera. Different groups of bacteria could be arranged in order of their decreasing sensitivity towards Md as follows: S. aureus, V. cholerae, E. coli and Shigella. The range of minimum inhibitory concentration (micrograms/ml) varied between 25 and 200 in most cases, although few strains were sensitive even at 10 micrograms/ml level of Md. 10 different bacteria sensitive to Md and a number of antibiotics when tested for their interaction with Md on one hand and any of the antibiotics of chemotherapeutic agents on the other, it was found that Md in combination with aminoglycosides and several chemotherapeutics showed enhancement of antibacterial effects resulting in synergism. The chemotherapeutic agents bromodiphenhydramine (Bn), diphenhydramine and methyldopa showed distinct synergism when tested in combination with Md. Determination of the area of inhibition zones for the degree of synergism with Md and streptomycin (Sm) produced statistically significant result (p less than 0.01) in comparison with their individual effect. This could also be corroborated by the fractional inhibitory concentration (FIC) index which was 0.49 for Sm-Md and 0.5 for Bn-Md combinations. The synergism of Sm-Md combination was confirmed by in vivo studies. PMID- 2905131 TI - Interaction of two barbiturates and an antihistamine on body temperature and motor performance of mice. AB - As an example for a drug combination used as a sedative (Vesparax) the actions of secobarbital (S), brallobarbital (B) and the antihistamine etodroxizine (E) were studied in mice after single and concomitant oral application. S and B caused a dose-dependent increase of exploratory locomotor performance enclosing a short period of locomotor depression. Such excitatory effect was suppressed by concomitant application. E produced a decrease in locomotion and--when added to S and B--enhanced their sedative effects. Explorative rearing was suppressed by low doses of S and B, by B, by E, and by all the combinations, whereas high single doses of S and B (20 mg/kg and 25 mg/kg, resp.) caused a triphasic temporal pattern. Motor coordination was investigated by means of fixed-bar and rotarod procedures. Increasing doses of S and B impaired motor performance within a small dose range. In concomitant applications rotarod performance revealed a dose additive synergism whereas the effect was moderately superadditive in the fixed bar test. Neither in single applications nor in combinations E showed any effects. Rectal temperature was poorly affected by the single drugs, but hypothermia was strongly enhanced by concomitant application of S and B and further potentiated by addition of E. The results suggest that responses to combinations of drugs even belonging to the same category cannot sufficiently be deduced from the single components alone. PMID- 2905132 TI - Soft drug derivatives related to perhexiline. Part I: In vitro studies. AB - A series of cyclohexylaralkylamines derived from perhexiline was synthesized according to the "soft drug" concept. An amide function was introduced as a labile centre to give non-toxic moieties in vivo after the "soft drugs" had attained their therapeutic aims. Compounds were evaluated for their alpha adrenolytic, calcium antagonist and vasodilator activities in vitro. Some of them, 2, 3, 7 and 15 on rat aorta had alpha-adrenolytic effects comparable to that of perhexiline. Most of them were about 10 times more active calcium antagonists on depolarized pig coronary artery than perhexiline. All derivatives produced concentration-related coronary dilation in the perfused guinea pig heart. Compound 2 was equipotent to perhexiline. The decrease in coronary resistance might, at least partly, be attributable to the alpha-blocking properties of the molecules. In conclusion, the introduction of an amide function into the perhexiline skeleton does not markedly alter the in vitro pharmacological properties. PMID- 2905133 TI - [The effect of temazepam on the functional capacity and metabolic and cardiocirculatory parameters in consideration of the "jet lag" syndrome]. AB - In a double-blind placebo controlled study, 14 male healthy volunteers were examined the morning after they had received an evening dose of 20 mg temazepam (Planum) with regard to functional capacity, cardial, cardiovascular and respiratory regulation as well as neuromuscular excitability and metabolic changes. After being exposed to the bicycle ergometer load, oxygen uptake, carbon dioxide output, glucose and lactate concentration were determined; furthermore the neuromuscular excitability of the musculus vastus medialis, musculus rectus femoris and musculus quadrizeps femoris was estimated. Despite unimportant capacity reductions (p greater than 0.05) concerning the maximum capacity (2.2%) as well as the maximum oxygen uptake (4.3%) under treatment with temazepam, there could not be proved any significant changes regarding cardiopulmonary and metabolic functions. On eastern and western flights, top athletes showed a very fast adaptation to the day-night rhythm without hang-over. PMID- 2905134 TI - [Plasma digoxin levels following treatment with metaclazepam]. AB - Nine cardiac patients treated with digitalis participated in a 3-week study with the aim to investigate whether digoxin (beta-acetyldigoxin) interacts with the new 1,4-benzodiazepine metaclazepam. Comparison of the plasma digoxin levels under placebo and metaclazepam treatment showed no statistically significant differences, i.e. no interactions between digoxin and metaclazepam were found. PMID- 2905135 TI - [The H1 and H2 histamine receptors]. AB - Histamine is a major mediator of the allergic reactions. Histamine have different actions: contraction of smooth muscles, vascular action, increase in gastric and adrenal medulla secretion. Effects on central or peripheral nervous system are discussed. The specific H1 or H2 activity explains the different configurations of histamine. The specificity of H1 receptors agonists is now well known: H1 activities have a positive charge on the side chain with an imidazole ring able to rotate around the axis of side chain. The contraction of smooth muscles is due to the action of H1 receptors agonists. Many doubts remain about the exact structures of the H2 receptors, and their agonists. Trough the H2 receptors occur dilatation of small arteries and capillaries, as well as an increase in gastric secretion. Subdivisions of H2 receptors have been, suggested. Recently H3 receptors have been described in the brain and in some peripheral tissues. Interrelations between H1 and H2 histamine receptors have been described as well as a feedback of synthesis and of histamine release. PMID- 2905136 TI - Histamine-induced regulation of IL-2 synthesis in man: characterization of two pathways of inhibition. AB - Histamine at molar concentrations ranging from 10(-5) to 10(-7) exerted an inhibitory effect upon IL-2 synthesis by peripheral blood mononuclear cells in normal man; two pathways of inhibition are described. The first pathway was found to alter the T4 lymphocytes which, in the system used in this study, synthesized nearly 90% of the total IL-2 production and had no suppressive activity. This suggests that histamine can act at the level of IL-2-producing cells. The second pathway of inhibition was related to induction of suppressor cells. Peripheral blood lymphocytes pre-incubated for 1 h with histamine 10(-5)-10(-7) M inhibited the IL-2 synthesis of normal autologous lymphocytes in a co-culture system. This activity was radio-resistant (1200 r) and mediated by T8 lymphocytes. These two pathways of inhibition were mediated by the specific interaction of histamine with H1- and H2-receptor-bearing mononuclear cells. PMID- 2905137 TI - [Lymphocyte system and relative resistance of inbred mice to Trypanosoma brucei brucei]. AB - The distribution of B-(Ig+) and T-(Thy1.2+, Lyt1+, Lyt2+) lymphocyte subsets in murine lymphoid organs was analysed by immunofluorescence (FACS) on cell suspensions throughout a primary infection of C3H/He (susceptible) and CBA/Ca (subtolerant) inbred mice with metacyclic Trypanosoma brucei brucei EATRO 1125. A direct correlation was observed between (1) the level of first-peak parasitaemia, (2) its subsequent control by the host and (3) survival time. In the course of the infection, the overall population of spleen and lymph node lymphocytes was subject to polyclonal activation whilst the proportion of differentiated B and T subsets decreased accordingly. No correlation was found between modulation of the lymphocyte system and susceptibility to trypanosomiasis. PMID- 2905138 TI - Structure and function of a thymic peptide is mimicked by Plasmodium falciparum peptides. AB - Numerous Plasmodium falciparum antigens contain repetitive amino acid sequences. Two blood stage antigens, Pf11-1 and Pf332, were characterized in our laboratories and present high cross-reactivities, defining a family of cross reacting antigens. In this report, we show that amino acid sequence homologies might explain these cross-reactivities, but that they extend to polypeptides from the host, namely thymosin-alpha 1 (T alpha 1). An antiserum raised in chickens and Saimiri monkeys against the synthetic Pf11-1 peptide cross-reacts with synthetic T alpha 1. Synthetic Pf11-1 and Pf332 peptides share some of the biological activities of T alpha 1. These results are discussed with respect to the mechanisms devised by malaria parasites for escape from the host immune response. PMID- 2905139 TI - Effect of plasma amino acid and hormone concentrations on renal plasma flow and glomerular filtration rate. AB - The effect of amino acid infusion on renal hemodynamics was examined in 13 healthy subjects. Seven subjects participated in the first experimental protocol: study 1 - amino acids were infused for 3 h to increase plasma amino acid levels 2 to 3-fold above baseline; study 2 - amino acids were infused with somatostatin and peripheral replacement of insulin, glucagon and growth hormone; and study 3 - somatostatin and hormones were infused as in study 2, but no amino acids were infused. During study 1 both glomerular filtration rate (GFR) and renal plasma flow (RPF) increased by 20%. In contrast, when amino acids were infused with somatostatin (study 2), neither GFR nor RPF changed from baseline. In study 3, somatostatin alone had no effect on GFR and RPF. In a second experimental protocol, 6 subjects were maintained for 7 days on a low protein diet (40 g/day); amino acids were infused as in study 1 before and after the protein restriction. Baseline GFR and RPF both decreased significantly after protein restriction. The response to amino acid infusion was not changed. These results indicate that: (1) hyperaminoacidemia causes a rise in both GFR and RPF; (2) the increase is likely to be mediated by some hormones whose secretion is inhibited by somatostatin, and (3) protein restriction causes a decline in GFR and RPF but fails to alter the renal hemodynamic response to amino acid infusion. PMID- 2905140 TI - Clinical and histopathological aspects of Kaposi's sarcoma in Africa: relationship with HIV serology. AB - From 1983 to 1987, 45 Kaposi's sarcomas (KS) were diagnosed at the University Hospital in Bangui; 37 cases were easily classified as either endemic or AIDS related KS on clinical grounds and HIV serology. Moreover, probably due to the stage at which patients consulted and lesions were sampled, noticeable histopathological differences were observed between the two clinical presentations. But for 8/45 which we classified as "borderline KS", strong discrepancies occurred between clinical aspects, patient evolution, HIV serology and histopathology. In two cases, HIV-positive patients had typical endemic non evolutive KS and have survived 15 and 36 months. PMID- 2905141 TI - Dementia as the primary manifestation of HIV2 infection in a Central African patient. PMID- 2905142 TI - Status of Hantavirus in the Central African Republic. PMID- 2905143 TI - Clinical pharmacology of mivacurium chloride (BW B1090U) infusion: comparison with vecuronium and atracurium. AB - Mivacurium chloride (BW B1090U) is a new, short-acting non-depolarizing neuromuscular blocking agent. It is a synthetic bis-benzylisoquinolinium diester, which is hydrolysed rapidly by plasma cholinesterase. This study compares mivacurium, atracurium and vecuronium by continuous i.v. infusion. The duration of mivacurium infusion ranged from 29.5 to 286 min. The steady state infusion rates necessary to maintain 95 (SEM 4)% twitch suppression were: mivacurium 8.3 (0.7) micrograms kg-1 min-1; atracurium 7.9 (0.4) micrograms kg-1 min-1; vecuronium 1.2 (0.3) micrograms kg-1 min-1. Following infusions of mivacurium, various recovery times (for example: 25-75%, 6.9 (0.3) min; 25-95%, 11.0 (0.4) min; 5-95% 14.5 (0.4) min) did not differ significantly from those following single bolus doses. Recovery times following cessation of mivacarium infusions were approximately 50% of those for equivalent durations of infusion of atracurium (10.9 (0.3) min for 25-75% recovery and 26.6 (0.4) min for 5-95% recovery). For vecuronium, corresponding recovery times were 13.8 (0.9) and 32.0 (1.2) min, respectively. Comparative recovery times for mivacurium were 40-50% of those for vecuronium. There was a significant correlation between the infusion rate of mivacurium required to maintain 95% twitch depression and the plasma cholinesterase activity of individual subjects. PMID- 2905144 TI - Post-tetanic count and intense neuromuscular blockade with vecuronium in children. AB - Sixty children undergoing surgery were allocated, according to weight, to three equal groups. Each child received a loading dose of vecuronium 80 micrograms kg-1 followed immediately by an infusion set initially at 1.4 micrograms kg-1 min-1. The subsequent intense neuromuscular blockade was assessed using the post-tetanic count (PTC). Maintaining the PTC between 5 and 15 ensured adequate paralysis which was antagonized easily 6-18 min after stopping the infusion. However, the duration of the initial intense block was unpredictable and the use of a peripheral nerve stimulator is advisable, particularly in smaller infants (less than 5 kg). The results suggest that vecuronium accumulated after 3 h infusion and that has less presynaptic effect than atracurium. PMID- 2905145 TI - Comparison of atracurium and vecuronium during anaesthesia for laparoscopy. AB - Atracurium 0.3 mg kg-1 and vecuronium 0.06 mg kg-1 were compared directly in a double-blind randomized trial during anaesthesia for laparoscopy in 57 healthy young women. The effects of the drugs were monitored using a portable electromyograph. Both drugs provided adequate intubating conditions at 3 min, and prompt antagonism of paralysis after administration of neostigmine, but recovery was significantly faster with vecuronium (mean time to 20% recovery of control electromyographic response: vecuronium 15.1 min; atracurium 20.6 min (P less than 0.001)). Atracurium caused a higher frequency of clinically observed allergoid reactions (21%) compared with vecuronium (3%). PMID- 2905146 TI - Antagonism of blockade produced by atracurium or vecuronium with low doses of neostigmine. AB - Neostigmine 1.25 mg or 0.625 mg was used to antagonize neuromuscular blockade produced by either atracurium 0.5 mg kg-1 or vecuronium 0.1 mg kg-1 in four groups of patients (n = 45) when the first EMG response of the train-of-four (A') had recovered to 10% of control (A). The time for A'/A and the train-of-four ratio (D'/A') to reach 70% was recorded. It was found that, after both atracurium and vecuronium, neostigmine 1.25 mg considerably accelerated recovery and, when compared with previous results, differed little from neostigmine 5.0 mg or 2.5 mg. Neostigmine 0.625 mg also significantly accelerated recovery after atracurium and was comparable to neostigmine 1.25 mg. However, with neostigmine 0.625 mg after vecuronium, recovery of D'/A' (but not A'/A) was little faster than spontaneous. Neostigmine 1.25 mg appears to be almost as effective as neostigmine 5.0 mg or 2.5 mg in antagonizing considerable block (90% depression of twitch height) produced by either atracurium or vecuronium, but neostigmine 0.625 mg is not sufficient, especially after vecuronium. PMID- 2905147 TI - Benzodiazepine premedication in minor day-case surgery: comparison of oral midazolam and temazepam with placebo. AB - Ninety day-case or short stay patients were allocated to three groups in a double blind study. The groups received oral midazolam 15 mg, oral temazepam 20 mg or placebo approximately 1 h before surgery. Midazolam was superior to temazepam regarding anxiolysis, sedation and amnesia, but temazepam was superior to placebo. However, delay in immediate and late recovery occurred significantly more often in the patients receiving midazolam than in those receiving temazepam or placebo. PMID- 2905148 TI - Central effects of beta-adrenoceptor antagonists. I--Performance and subjective assessments of mood. AB - 1. Central effects of the beta-adrenoceptor antagonists, propranolol (40, 80 and 160 mg) and atenolol (50 and 100 mg) were studied in 12 healthy male subjects. Two placebo ingestions and an active control (oxazepam 15 mg) were included. Single doses were administered double-blind at 11.00 h, and assessments of performance and subjective feelings were made before, 2 h and 4 h after ingestion. 2. Performance was measured using letter cancellation, digit symbol substitution, continuous attention, choice reaction time, finger tapping, short term and immediate memory, critical flicker fusion and two flash fusion. Subjective feelings were assessed using twelve visual-analogue scales. 3. Oxazepam impaired performance at letter cancellation (P less than 0.001), digit symbol substitution (P less than 0.05), continuous attention (P less than 0.001), immediate recall (P less than 0.05) and finger tapping (P less than 0.05), but neither of the beta-adrenoceptor antagonists affected these measures. Propranolol (40 and 160 mg) also impaired short term memory (P less than 0.05), though it was not possible to establish this effect with atenolol. 4. Subjective alertness was reduced by oxazepam (P less than 0.01) and atenolol (P less than 0.05), while propranolol (40 mg) reduced anxiety (P less than 0.01) and propranolol (80 mg) impaired ability to concentrate (P less than 0.05). 5. The results suggest that both lipophilic and hydrophilic antagonists modify the central nervous system, though impairment may be difficult to establish with conventional tests. The observations on memory and alertness suggest that the central effect of beta adrenoceptor antagonists may be subtle. PMID- 2905149 TI - Central effects of beta-adrenoceptor antagonists. II--Electroencephalogram and body sway. AB - 1. Effects of the beta-adrenoceptor antagonists, propranolol (40, 80 and 160 mg) and atenolol (50 and 100 mg) on the electroencephalogram and on body sway, were studied in 12 healthy male subjects. The study was double-blind, and included two placebos and an active control, oxazepam (15 mg). Medication was ingested at 11.00 h, and assessments were made before, and at 2 h and 4 h after ingestion. 2. All doses of both beta-adrenoceptor antagonists modified the electroencephalogram, and the changes reported were statistically significant at probability levels of less than 5%. The circadian rise in alpha activity was reduced by both beta-adrenoceptor antagonists as well as by oxazepam. Atenolol also decreased beta activity. 3. Body sway was modified by atenolol and oxazepam (P less than 0.05). The increase with oxazepam was most marked in the low frequency component (0.05-2.25 Hz) of the spectrum, while atenolol modified only the component of higher frequency (2.25-4.0 Hz). 4. These observations suggest that propranolol and atenolol have a sedative effect, and that hydrophilic antagonists are unlikely to be free of central activity. The changes in body sway could imply that peripheral mechanisms may be modified at least with atenolol. PMID- 2905150 TI - The pharmacokinetics, antihistamine and concentration-effect relationship of ebastine in healthy subjects. AB - 1. The kinetics and effects of ebastine 10 and 50 mg were studied after oral dosing in healthy subjects. 2. The parent drug was extensively metabolised during the first pass to its carboxylic acid derivative, carebastine. 3. The pharmacokinetics of carebastine were linear over the dose range studied and the terminal elimination half-life was 10.6 +/- 2.6 and 12.5 +/- 1.9 h respectively after 10 and 50 mg of ebastine. 4. Antihistamine (H1-receptor) activity was examined with intradermal histamine (2 micrograms). Oral ebastine reduced the histamine wheal area for up to 24 h and also reduced subjective local pain. 5. Antihistamine activity correlated well with plasma levels of carebastine in individual subjects. 6. Ebastine appears to have potential as an antihistamine for once a day dosing. PMID- 2905151 TI - Ebastine: the effect of a new antihistamine on psychomotor performance and autonomic responses in healthy subjects. AB - 1. Ebastine, through its carboxylic acid metabolite has antihistamine (H1 receptor) activity in man. 2. We have examined in a single blind placebo controlled study the effects of 10 mg and 50 mg of ebastine on cardiovascular, autonomic and psychomotor function in healthy subjects. 3. Ebastine had no effect on blood pressure or heart rate and there was no evidence of any anticholinergic activity on circulatory reflexes or salivation. 4. Ebastine did not impair psychomotor performance as assessed by critical flicker fusion at either dose. 5. Ebastine 10 mg had no effect on sedation measured by visual analogue scale or direct questioning, however ebastine 50 mg did cause a modest increase in indices of sedation. 6. Ebastine did not have detectable sedative properties at the 10 mg dose where long-lasting antihistamine effects can be demonstrated. PMID- 2905152 TI - Reversal of histamine-induced bronchoconstriction by the H1-receptor antagonist levocabastine: a potential model for efficacy in anaphylaxis. AB - 1. The rate of onset and magnitude of the effect of levocabastine, a potent H1 receptor antagonist, in reversing histamine-induced bronchoconstriction were determined in a double-blind cross-over trial against saline placebo. Histamine was administered by nebuliser so that forced expiratory volume in 1 second (FEV1) was reduced to 80-75% of baseline FEV1 in 10 men with mildly or moderately responsive airways and the effects of intravenous injection of saline or saline + 200 micrograms levocabastine were studied. 2. The maximum rate of recovery of FEV1 was 7[2-10]% min-1 (median [range]) in the first 5 min after levocabastine injection, but only 4[1-7]% min-1 after saline alone (P less than 0.05). 3. The median area under the recovery curve of FEV1 from 0 to 30 min after injection was 405 [228-498]% basal FEV1 X min after levocabastine and 301[98-502]% basal FEV1 X min after saline alone (P less than 0.002). 4. FEV1 returned to 90% of baseline within 30 min in all subjects after levocabastine, but not after saline alone (P less than 0.002). 5. Histamine-induced bronchoconstriction was relieved more quickly by levocabastine than saline alone. This model may have application to the study of drugs used in the treatment of anaphylaxis. PMID- 2905153 TI - A study of the clinical efficacy of azelastine in patients with extrinsic asthma, and its effect on airway responsiveness. AB - 1. The effect of 4.4 mg azelastine administered orally on airway responsiveness, skin prick testing, daily peak expiratory flow rates and symptoms of asthma was compared with placebo in a 7 week double-blind, parallel group study of 24 patients with extrinsic asthma. The study was in two parts: a 2 week assessment period, during which all patients received placebo tablets but recorded daily peak flow rates (PEFRs) and symptoms, preceding the 7 week double-blind comparison. 2. Azelastine, 4.4 mg, significantly decreased airway responsiveness to histamine compared with placebo both after a single dose (P less than 0.001), and following 7 weeks continuous treatment (P less than 0.02). Airway responsiveness to methacholine was not altered by administration of azelastine compared with placebo. 3. Skin prick test weal diameters to both allergen and histamine were significantly reduced after both a single dose and following 7 weeks continuous therapy treatment with azelastine. 4. There was a significant improvement in both the mean of the morning and the evening peak flow rates recorded during the last week compared with the first week of the study in the group receiving 4.4 mg of azelastine twice daily compared with placebo. Scores for wheeze were significantly reduced during the final 3 weeks of the study in patients receiving azelastine compared both with those receiving placebo and with the first week of the study (P less than 0.05, P less than 0.01). Consumption of inhaled bronchodilators fell significantly during the study in the group receiving azelastine therapy (P less than 0.05); no such fall occurred in the placebo treated patients. 5. A bitter metallic taste was reported by 58% of patients who received azelastine therapy. PMID- 2905154 TI - Antihypertensive efficacy of the calcium-antagonist felodipine in patients with persisting hypertension on beta-adrenoceptor blocker therapy. The Canadian Felodipine Study Group. AB - 1. The antihypertensive efficacy of two different doses of the calcium antagonist felodipine was evaluated in patients with hypertension persisting despite beta adrenoceptor blocker therapy. Following a single-blind placebo period of 4 weeks, patients were randomized to placebo (n = 36), felodipine 5 mg twice daily (n = 39) and felodipine 10 mg twice daily (n = 35) for another 4 weeks. beta adrenoceptor blocker therapy remained unchanged throughout the study. 2. Effects on blood pressure (BP) were evaluated after the first dose and after chronic dosing at 2 h after dosing and the end of the dosing interval (12 h). 3. Felodipine decreased systolic and diastolic BP by 30-35/20-25 mm Hg at 2 h. These decreases were similar after acute and chronic treatment. Twelve hours after dosing, decreases of 15-20/10-15 mm Hg were observed compared to 10/5 mm Hg on placebo, and half of the patients still had a controlled BP (supine diastolic BP less than 90 mm Hg). BP responses were rather similar for both doses of felodipine at 2 and 12 h. 4. Multiple regression analysis showed that both initial BP level and plasma felodipine concentrations were significant predictors of the BP response to felodipine, but age was not. 5. Adverse effects attributed to felodipine were mainly related to vascular symptoms (primarily flushing and ankle swelling); these occurred in about 30% of patients, and were pronounced in three patients (4%). 6. Felodipine is therefore highly effective in lowering BP of hypertensive patients on chronic beta-adrenoceptor blocker therapy, with no evidence for a gradual lowering of the BP or for development of tolerance. Both initial BP level and plasma concentrations are better indicators of antihypertensive efficacy of this calcium antagonist than age. PMID- 2905155 TI - A pilot study of terfenadine as adjunctive therapy in rheumatoid arthritis. PMID- 2905156 TI - Torsade de pointes ventricular tachycardia associated with astemizole overdose. PMID- 2905157 TI - First European review of terazosin. Proceedings of a symposium. Reykjavik, Iceland, 29th-31st May 1987. PMID- 2905158 TI - Review of central haemodynamic effects of alpha-blockers and their future use in hypertension. PMID- 2905159 TI - Comparison of the haemodynamic effects of alpha- and beta-blockade in essential hypertension. PMID- 2905160 TI - Terazosin in mild hypertension: experience in open trials. PMID- 2905161 TI - A review of the effects of antihypertensive treatment with alpha 1-adrenoceptor antagonists on plasma lipid profiles. PMID- 2905162 TI - Terazosin (Hytrin): cumulative experience of clinical trials in the USA for the treatment of mild to moderate essential hypertension. PMID- 2905163 TI - Glutathione and related enzyme activity in human lung cancer cell lines. AB - Glutathione levels were measured in 30 human lung cancer lines. Lower levels were detected in cell lines derived from small cell lung cancer specimens compared to non-small cell lines (mean 42 vs. 130 nmol mg-1 protein, P = 0.005). However, no difference were detected between cell lines derived from previously untreated patients, compared to those derived from patients who had received chemotherapy. Non-small cell lines were found to have increased activity of 4 detoxification enzymes compared to small cell lines, although these differences did not reach statistical significance: glutathione transferase activity (69 vs. 36 units, P = 0.137), glutathione reductase (139 vs. 82 units, P = 0.05), gamma-glutamyl transpeptidase (9.39 vs. 3.03 units, P = 0.072) and superoxide dismutase (20 vs. 13.6 units, P = 0.137). As the cell lines exhibit a similar chemosensitivity pattern to that observed in clinical practice, these differences in glutathione and detoxification enzyme levels may prove to be important indicators of intrinsic drug resistance often seen in patients with non-small cell lung cancer. PMID- 2905164 TI - A study of local immunity in psoriasis. AB - We have studied biopsies of lesional skin with monoclonal and polyclonal antibodies to determine the nature of the infiltrate in different forms of psoriasis. In guttate psoriasis the number of Langerhans cells (LC) was not increased and CD8+ cells predominated, however, most CD4+ cells were activated. In erythrodermal psoriasis some CDI+ cells were found in the dermis although CD8+ cells predominated and were activated. In palmo-plantar psoriasis LC were found in the epidermis and superficial dermis and CD4+ cells were more numerous than CD8+ cells, some in turn expressing HLA-DR. In flexural psoriasis the LC formed clusters in the epidermis, and activated CD4+ cells predominated. In psoriasis vulgaris CD4+ cells predominated over CD8+ although the latter were activated. Our observations tend to support Valdimarsson's hypothesis on the immune basis of psoriasis, but we believe that two cycles coexist in psoriasis--one inflammatory and the other immunological--and that interaction between these leads to epidermal hyperproliferation. PMID- 2905165 TI - Carrier detection strategy in haemophilia A: the benefits of combined DNA marker analysis and coagulation testing in sporadic haemophilic families. AB - A province wide study of carrier detection methods in haemophilia A is reported. The principal objective of this project was to compare the relative merits of coagulation testing and DNA marker analysis in carrier diagnosis for a large unselected haemophilic population. Factor VIII:C (F.VIII:C) and von Willebrand factor antigen (vWf:Ag) were measured on plasma samples sent to a central laboratory. Coagulation results were analysed by a logistic regression model of discrimination. Of 91 potential carriers tested, 15% had indeterminate coagulation test carrier probabilities. Two restriction fragment length polymorphisms were analysed in 123 women (42 obligate carriers and 81 potential carriers). The BcII polymorphism within the F.VIII gene and the locus DXS 52, approximately 5 cM (centimorgan) from F.VIII were used as DNA markers. Of the 81 potential carriers tested with RFLP analysis, a carrier diagnosis was achieved in 52%. Studies with the F.VIII intragenic BgII polymorphism in 23 of these families gave no additional information. Thirty-nine potential carriers remained undiagnosed after DNA marker analysis. Twenty-seven of these women were from families with a sporadic case of haemophilia. In this group of 27 women, 14 were found to have high probability carrier estimates derived from their coagulation tests. Combined coagulation and RFLP data was available in 42 potential carriers. Disagreement between DNA and coagulation carrier diagnoses was found in four instances. In each case, the coagulation data resulted in a carrier probability of indeterminate value. This study emphasizes some of the limitations associated with DNA marker linkage analysis as it pertains to haemophilia A carrier detection. Where a previous family history exists and appropriate females are informative for the DNA markers, this type of analysis is very productive. However, large numbers of potential carriers from 'sporadic' haemophilia families were a factor in this project. With this in mind, an optimal service for haemophilia A carrier diagnosis must continue to offer reliable coagulation test probabilities in addition to DNA marker studies. PMID- 2905166 TI - Identification of aspartate-184 as an essential residue in the catalytic subunit of cAMP-dependent protein kinase. AB - The hydrophobic carbodiimide dicyclohexylcarbodiimide (DCCD) was previously shown to be an irreversible inhibitor of the catalytic subunit of cAMP-dependent protein kinase, and MgATP protected against inactivation [Toner-Webb, J., & Taylor, S. S. (1987) Biochemistry 26, 7371]. This inhibition by DCCD indicated that an essential carboxyl group was present at the active site of the enzyme even though identification of that carboxyl group was not possible. This presumably was because a nucleophile on the protein cross-linked to the electrophilic intermediate formed when the carbodiimide reacted with the carboxyl group. To circumvent this problem, the catalytic subunit first was treated with acetic anhydride to block accessible lysine residues, thus preventing intramolecular cross-linking. The DCCD reaction then was carried out in the presence of [14C]glycine ethyl ester in order to trap any electrophilic intermediates that were generated by DCCD. The modified protein was treated with trypsin, and the resulting peptides were separated by HPLC. Two major radioactive peptides were isolated as well as one minor peptide. MgATP protected all three peptides from covalent modification. The two major peaks contained the same modified carboxyl group, which corresponded to Asp-184. The minor peak contained a modified glutamic acid, Glu-91. Both of these acidic residues are conserved in all protein kinases, which is consistent with their playing essential roles. The positions of Asp-184 and Glu-91 have been correlated with the overall domain structure of the molecule. Asp-184 may participate as a general base catalyst at the active site. A third carboxyl group, Glu-230, also was identified.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2905167 TI - Characterization of the ATP synthase of Propionigenium modestum as a primary sodium pump. AB - The ATP synthase (F1F0) of Propionigenium modestum has been purified to a specific ATPase activity of 5.5 units/mg of protein, which is about 6 times higher than that of the bacterial membranes. Analysis by SDS gel electrophoresis indicated that in addition to the five subunits of the F1 ATPase, subunits of Mr 26,000 (a), 23,000 (b), and 7500 (c) have been purified. The ATPase activity of F1F0 was specifically activated about 10-fold by Na+ions. The enzyme was strongly inhibited by dicyclohexylcarbodiimide, venturicidin, tributyltin chloride, and azide. After incubation with [14C]dicyclohexylcarbodiimide, about 3-4 mol of the inhibitor was bound per 500,000 g of the enzyme. The radioactive label was specifically bound to submit c. These subunits form stable aggregates which resist dissociation by SDS at 100 degrees C. The monomer is formed upon heating with SDS to 121 degrees C or by extraction of the membranes with chloroform/methanol. The ATP synthase was incorporated into liposomes by a freeze thaw-sonication procedure. The reconstituted proteoliposomes catalyzed the transport of Na+ions upon ATP hydrolysis. The transport was completely abolished by dicyclohexylcarbodiimide. Whereas monensin prevented the accumulation of Na+ions, the uptake rate was stimulated 4-5-fold in the presence of valinomycin or carbonyl cyanide m=chlorophenylhydrazone. These results indicate an electrogenic Na+ transport and also that it is a primary event and not accomplished by a H+-translocating ATP synthase in combination with a Na+/H+ antiporter. PMID- 2905169 TI - Stability and covalent modification of P-glycoprotein in multidrug-resistant KB cells. AB - An antipeptide antibody (P7) to P-glycoprotein has been produced by immunizing rabbits with a synthetic peptide. Antibody P7 is directed against the amino terminal region of P170 (residues 28-35). The antibody immunoprecipitates a 170 kDa P-glycoprotein from extracts of drug-resistant KB-V1 cells that is not present in the drug-sensitive cell line KB-3-1. Antibody P7 was used to quantitate the amount of P-glycoprotein present in drug-resistant KB lines at various levels of resistance and to demonstrate the presence of P-glycoprotein in NIH 3T3 cells transfected with a cloned MDR1 cDNA or human genomic DNA encoding MDR1. Pulse-chase labeling experiments demonstrated that P-glycoprotein is synthesized as a 140-kDa precursor which is slowly converted over 2-4 h to a 170 kDa glycoprotein. Tunicamycin treatment blocks the conversion of the precursor to the mature form, and removal of N-linked oligosaccharides with Endo F reduces the relative molecular weight of P-glycoprotein to 140K. The mobility of mature P glycoprotein is unaffected by treatment with neuraminidase and Endo H. These data indicate that P-glycoprotein is N-glycosylated and contains little or no neuraminic acid. P-Glycoprotein is also phosphorylated, and the extent of phosphate incorporated is proportional to the amount of protein present in drug resistant cells. PMID- 2905168 TI - Energy-induced modulation of the kinetics of oxidative phosphorylation and reverse electron transfer. AB - The kinetics of ATP synthesis by bovine heart submitochondrial particles (SMP) are modulated by the rate of energy production by the respiratory chain between two fixed limits characterized by apparent KmADP = 2-4 microM and Vmax approximately 200 nmol of ATP min-1 (mg of SMP protein)-1 at low energy levels and apparent KmADP = 120-160 microM and Vmax = 11,000 nmol of ATP min-1 (mg of SMP protein)-1 at high energy levels. These data indicate that KmADP and Vmax increase approximately 50-fold each; therefore, there is essentially no change in the catalytic efficiency of the ATP synthase complex in going from one extreme to the other. At intermediate rates of energy production, the kinetic data required introduction of a third, intermediate KmADP. A KmADP of 10-15 microM fitted all the data reported here and previously [Matsuno-Yagi, A., & Hatefi, Y. (1986) J. Biol. Chem. 261, 14031-14038]. However, this is not meant to suggest that there is a fixed intermediate KmADP, as the transition from one fixed limit to the other may be fluid or involve more than one intermediate state. In addition, it has been shown that kinetic plots of SMP-catalyzed and ATP-driven reverse electron transfer from succinate to NAD are curvilinear and resolvable into a minimum of two apparent KmNAD values of about 20-30 and 200-300 microM. These results have been discussed in relation to the three potentially active catalytic sites of F1-ATPase and the structure of the NADH:ubiquinone oxidoreductase complex, the curvilinear kinetics of ATP hydrolysis, and changes in KmADP and KmPi in photophosphorylation as affected by the duration and intensity of light. PMID- 2905170 TI - Kinetic characterization of the carbon monoxide-acetyl-CoA (carbonyl group) exchange activity of the acetyl-CoA synthesizing CO dehydrogenase from Clostridium thermoaceticum. AB - CO dehydrogenase from Clostridium thermoaceticum is a nickel-containing enzyme that catalyzes both the reversible conversion of CO2 to CO (for incorporation into the carbonyl group of acetate) and the synthesis of acetyl-CoA from methyl corrinoid, CO, and CoASH. The latter activity is conveniently assayed by monitoring the exchange of [1-14C]acetyl-CoA (carbonyl group) with 12CO. Kinetic parameters for the highly oxygen sensitive exchange activity have been determined: Km (acetyl-CoA) = 600 microM; Vmax = 440 min-1. In addition, coenzyme A analogues have been tested as inhibitors of the exchange to probe the active site of the enzyme; each has no effect on the CO2 in equilibrium CO activity of CO dehydrogenase. Coenzyme A, the substrate for acetate biosynthesis, is a potent competitive inhibitor, KI = 7 microM. Comparison of this value with that for desulfo-CoA (KI = 6000 microM) suggests that a key mode of binding is through the sulfur atom, possibly to a metal site on the enzyme. The relatively high affinity of the enzyme for CoASH relative to acetyl-CoA is consistent with its proposed operation in the acetogenic direction. The differential sensitivity to oxygen and storage of the two activities of CO dehydrogenase as well as the contrasting effect of coenzyme A inhibitors suggests that acetate assemblage occurs at a site distinct from that for CO dehydrogenation. PMID- 2905171 TI - Protein-protein interactions of yeast DNA polymerase III with mammalian and yeast proliferating cell nuclear antigen (PCNA)/cyclin. AB - We have previously reported the purification of yeast analogs to mammalian DNA polymerase delta and proliferating-cell nuclear antigen (PCNA)/cyclin: DNA polymerase III and yeast PCNA, respectively. Through the use of gel-filtration chromatography, we have studied the interaction of the model template-primer system poly(dA).(dT)16 (40:1) with yeast DNA polymerase III and with PCNAs. Yeast DNA polymerase III binds to the DNA in the absence of yeast PCNA/cyclin, but comigration of either yeast or calf thymus PCNA/cyclin with the DNA requires the additional presence of yeast DNA polymerase III. We could also isolate a DNA-calf thymus DNA polymerase delta-calf thymus PCNA/cyclin complex. From these data, we propose that PCNA/cyclin is involved not in the binding step of the polymerase to the template-primer, but in the elongation step. The 3'----5' exonuclease associated with yeast DNA polymerase III acts in a distributive manner on poly(dA).(pT)16, and dissociates from the DNA when addition of dTTP allows switching from the exonuclease to the polymerase mode. Addition of PCNA/cyclin had no effect on these activities. PMID- 2905172 TI - Identification of cellular components required for SV40 DNA replication in vitro. AB - To investigate the cellular proteins involved in simian virus 40 (SV40) replication, extracts derived from human 293 cells have been fractionated into multiple components. When such fractions are combined with the virus-encoded T antigen (TAg) and SV40 origin containing plasmid DNA, efficient and complete replication is achieved, while each fraction alone is inactive. At present, a minimum of eight such cellular components have been identified. Previous experiments have demonstrated one of these to be the cell-cycle-regulated proliferating-cell nuclear antigen (PCNA). As PCNA has been identified as a processivity factor for DNA polymerase delta, we suggest that both polymerases alpha and delta are involved in this system. Three further fractions have been identified. One is a partially purified fraction which, under certain conditions, is required with TAg for the formation of a pre-synthesis complex of proteins at the replication origin. The second of these factors, RF-A, is a complex of three polypeptides which may function as a eucaryotic SSB. The third, RF-C, is a factor which is required, with PCNA, for coordinated leading- and lagging-strand synthesis at the replication fork. Complete synthesis and segregation of the daughter molecules also requires the presence of topoisomerases I and II. These results suggest a model for DNA synthesis which involves multiple stages prior to and during replicative DNA synthesis. PMID- 2905173 TI - The enhancer in an MHC class II gene, in vitro and in mouso. AB - The E alpha class II gene of the major histocompatibility complex is expressed in a variety of immunocompetent cells. Part of the control of tissue-specific expression is mediated by a block of sequences found far upstream of the transcriptional startsite; this stretch is necessary for expression in the B lymphocytes of transgenic mice, but largely dispensable elsewhere. We review the evidence for the role of this region in E alpha transcription in transgenic animals, as well as data from transfections into tissue-culture cells, which indicate that this region has non-specific enhancer activity. We discuss possible models to explain how a non-specific enhancer can participate in cell-specific control. PMID- 2905174 TI - Genetic variability of proto-oncogenes for breast cancer risk and prognosis. AB - This paper summarizes the results of a study on human breast cancers performed mainly at the Centre Rene Huguenin in collaboration with other American and French groups, and supported in part by a Grant from the Association pour la Recherche sur le Cancer (ARC) Villejuif. During this work, the following conclusions emerged: c-myc proto-oncogene amplification is a common alteration in ductal invasive tumors, more frequently found in recurrent and metastatic tumors, suggesting a role for c-myc in tumor progression. However, in the current state of our study, it does not appear to be linked to prognosis; parts of the short arm of chromosome 11 are deleted in 20% of tumors resulting in hemizygosity for several genes (c-ha-ras, beta globin, pTH, calcitonin, catalase). These deletions seem to be linked with aggressiveness of tumors; a restriction fragment length polymorphism (RFLP) study of c-ha-ras has shown a significant association of the frequency of rare ha-ras alleles in cancer patients compared to that of normal individuals. Although this result is currently a matter of controversy, further studies must be independently repeated to be conclusive; -- another RFLP was found in c-mos proto-oncogene, which is detected only in patients with breast cancers or other types of tumors. The molecular basis for this RFLP has been elucidated. The significance of this association is unknown. PMID- 2905175 TI - Evidence for the regulation of fatty acid utilization in human sperm by docosahexaenoic acid. AB - The effects of stearic (18:0), linolenic (18:3), and docosahexaenoic (22:6) acids on palmitoyl coenzyme A (CoA) formation by a long-chain fatty acid:CoASH ligase (adenosine monophosphate) (E. C. 6.2.1.3-enriched fraction from human spermatozoa were studied. Both 18:0 and 18:3 were competitive inhibitors for palmitic (16:0) acid activation with Kis of 17.7 and 5.7 microM, respectively. In contrast, 22:6 was a noncompetitive inhibitor demonstrating a Ki of 9.5 microM. These data coupled with previous studies support the conclusion that 16:0, 18:0, and 18:3 and other saturated and unsaturated fatty acids are activated by the same ligase enzyme in sperm. Although the kinetics and interactions of 22:6 are unique compared to the other fatty acids found in sperm phospholipids, we cannot discern from our data if it is activated by a separate enzyme. We propose that 22:6, or a metabolite of 22:6, may regulate free fatty acid utilization in human sperm and that this hypothesis may provide an enzymatic explanation for the changes observed in phospholipid-bound fatty acids during the epididymal maturation of sperm. PMID- 2905176 TI - Effects of pH and temperature on cardioactive polypeptides from sea anemones: a 1H-NMR study. PMID- 2905177 TI - Effects of alloxan-induced diabetes on somatostatin binding to cytosolic components of rabbit gastric fundic mucosa. AB - Diabetes was induced by administration of alloxan (150 mg/Kg) to 24 h-fasted rabbits. Somatostatin-like immunoreactivity (SLI) and cytosolic binding sites for somatostatin in gastric fundic mucosa were studied using radiolabelled Tyr11 somatostatin. Three months after the onset of the disease, the specific binding of somatostatin to these sites was seen to be significantly lower, due to a reduction in the number (but not the affinity) of specific somatostatin binding sites of high-affinity and a disappearance of the specific somatostatin binding sites of low-affinity. These changes were associated with an increase in the SLI concentration in both gastric fundic mucosa and plasma. PMID- 2905178 TI - [The proliferative potential of hematopoietic stem cells (CFUs) during serial passage in irradiated mice as foci of ectopic hematopoiesis]. AB - During serial passages of hemopoietic tissue as a whole ectopic hemopoietic site under renal capsule of irradiated mice gradual decrease of proliferative potential of CFUs has been observed. The results suggest that the most probable cause of such decline is random loss of precursor cells with high but limited proliferative potential during serial passages of hemopoietic tissue. PMID- 2905179 TI - [Genes of hereditary diseases that predispose to tumors]. AB - Ten genes responsible for the increase of specific tumor incidence in affected families have been localized on the human genetic map. This knowledge not only provides the mean of a precise genetic counselling but also opens a way for further investigating the genetic mechanisms of these disorders. Usually, it is admitted that dominantly inherited familial predisposition to tumors is due to a defective tumor suppressor gene. This hypothesis is almost certain for familial retinoblastoma, highly probable for hereditary nephroblastoma and possible for neurofibromatosis type II. In contrast, the gene for familial polyposis coli shows some characteristics of activated oncogenes. PMID- 2905180 TI - Human retroviruses. AB - After many unsuccessful years of searching, the first pathogenic human retrovirus, the human T-cell leukaemia lymphoma virus (HTLV-I), was reported as recently as 1980 and since that time has been causally linked to the adult T-cell leukaemia lymphoma syndrome. A second HTLV (HTLV-II) isolated shortly afterwards is less clearly linked to some leukaemic and chronic lymphoid malignancies. The second major family of human retroviruses are the human immunodeficiency viruses (HIV) the first group of isolates (HIV-I) of which cause the acquired deficiency syndrome (AIDS). A second group of these viruses (HIV-II), have recently been identified in West Africa. They appear to be less clearly associated with disease and more similar in molecular structure to the Simian immunodeficiency viruses. AIDS has now become a major global pandemic, and vaccine and therapeutic strategies are urgently being investigated in an effort to control the disease. Unfortunately, current results are not very encouraging. In the meantime, preventative and educational measures are of utmost priority in order to prevent further spread. It is not unlikely that new human retroviruses will be discovered over the next few years. PMID- 2905181 TI - Controlling the carcinoid syndrome. PMID- 2905182 TI - Evidence that the population of postjunctional-adrenoceptors mediating contraction of smooth muscle in the rabbit isolated ear vein is predominantly alpha 2. AB - 1. Noradrenaline (NA), phenylephrine and UK-14304 elicited concentration dependent contractions of the rabbit isolated ear vein of similar maximal magnitude. The rank order of potency, UK-14304 greater than noradrenaline greater than phenylephrine, is consistent with that of an effect mediated through an alpha 2-subtype. 2. The potent and highly selective alpha 1-adrenoceptor antagonists prazosin and YM-12617, at concentrations as high as 1 microM, produced less than a 4 fold rightward displacement of the NA concentration response curve. 3. The selective alpha 2-adrenoceptor antagonists rauwolscine, Wy 26703 and CH-38083 antagonized responses to noradrenaline in a competitive manner. For all three antagonists, the pA2 values were consistent with an effect at alpha 2-adrenoceptors. However, 0.1 microM YM-12617 increased the potency of rauwolscine 2 fold indicating the presence of a small population of postjunctional alpha 1-adrenoceptors. 4. The relative antagonist potency of the yohimbine diastereoisomers rauwolscine and corynanthine against noradrenaline (rauwolscine 30 fold greater than corynanthine) is also consistent with an effect at alpha 2-adrenoceptors. 5. Contractions elicited by noradrenaline in the rabbit isolated ear vein appear to be mediated predominantly by postjunctional alpha 2 adrenoceptors. PMID- 2905183 TI - The beta 1-adrenoceptor antagonist, betaxolol, is not released from the heart of the anaesthetized dog during sympathetic nerve stimulation. AB - 1. We investigated the hypothesis that the beta 1-adrenoceptor antagonist, betaxolol, can be accumulated by cardiac sympathetic nerve endings and then released together with noradrenaline during accelerans nerve stimulation. 2. Dogs were chronically treated with betaxolol (1 mg kg-1 daily, s.c.) for 7 days. Twenty four hours after the last dose, there was a significant retention of betaxolol in the heart of these dogs treated chronically with the beta 1 adrenoceptor antagonist. However, during in vivo accelerans nerve stimulation, the concentration of betaxolol in the coronary sinus was not modified, whereas the noradrenaline concentration increased significantly. 3. Chronic betaxolol treatment antagonized the tachycardia induced by electrical stimulation of the cardiac accelerator nerves or by intravenous isoprenaline. However, the tachycardia induced by nerve stimulation was not antagonized to a greater extent than that induced by isoprenaline. 4. These findings are discussed in relation to a similar in vivo study in dogs treated with propranolol, in which the drug was found to be released into the coronary circulation during stimulation of the accelerans nerve. PMID- 2905184 TI - Agonist and antagonist characterization of a putative adrenoceptor with distinct pharmacological properties from the alpha- and beta-subtypes. AB - 1. Experiments were done to characterize a putative adrenoceptor which functions to inhibit longitudinal muscle tension development in the guinea-pig ileum. Several phenylethylamine based agonists were investigated: BRL 37344, (-) isoprenaline, (+)-isoprenaline, noradrenaline, adrenaline, and fenoterol. Propranolol and nadolol were tested as antagonists. Agonist-induced inhibition of the contractile response to histamine was measured under equilibrium conditions with alpha-adrenoceptors and muscarinic cholinoceptors inhibited. 2. Inhibitory responses were obtained to (-)-isoprenaline and BRL 37344 that were resistant to beta-adrenoceptor blockage with propranolol (5 microM) and nadolol (10 microM). These resistant responses were antagonized by much higher concentrations of nadolol (30 to 1000 microM) yielding apparent pA2 values for nadolol of 4.31 with (-)-isoprenaline as the agonist, and 4.68 with BRL 37344 as the agonist. Similar apparent pA2 values for nadolol at the putative adrenoceptor were obtained with noradrenaline (4.79), adrenaline (4.68), and fenoterol (4.38). 3. The order and relative potency of agonists at the putative adrenoceptor was: BRL 37344 (20) greater than (-)-isoprenaline (8) greater than noradrenaline (1) greater than adrenaline (0.5) greater than fenoterol (0.35) greater than (+)-isoprenaline (0.27). 4. The resistance to blockade by propranolol (5 microM), the low affinity of nadolol, and the order and relative potency of agonists, suggest the presence of an adrenoceptor with distinct pharmacological characteristics from currently defined alpha- and beta-adrenoceptors. PMID- 2905185 TI - Amino acid pharmacology in neocortical slices: evidence for bimolecular actions from an extension of the Hill and Gaddum-Schild equations. AB - 1. The equivalent circuit of the cortical slice preparation has been analysed to show that the measured d.c. voltages can be used to estimate the Hill coefficient for ligands acting on the pyramidal cell bodies. 2. The Gaddum-Schild equation for agonist-antagonist interactions has been modified for applications in which the Hill coefficient is not equal to 1. 3. The equations obtained have been applied to recent data of Burton et al. (1988). The results provide evidence for a bimolecular action of the agonists N-methyl-D-aspartate (NMDA) and quinolinic acid and the antagonists kynurenic acid and 2-amino-5-phosphono-pentanoic acid at NMDA receptors on mouse neocortical pyramidal cells. PMID- 2905186 TI - A comparison between the in vivo and in vitro activity of five potent and competitive NMDA antagonists. AB - 1. Phosphonate analogues of glutamate have been tested and compared as N-methyl-D aspartate (NMDA) antagonists in electrophysiological and binding experiments. The compounds tested were three established NMDA antagonists: D-2-amino-5 phosphonopentanoate (D-AP5), DL-2-amino-7-phosphonoheptanoate (DL-AP7), 3-(2 carboxypiperazin-4-yl)propyl-1-phosphonate (CPP), and two novel putative NMDA antagonists: 3-(2-carboxypiperidin-4-yl)propyl-1-phosphonate (CPPP) and 3-(2 carboxy-piperidin-4-yl)methyl-1-phosphonate (CPMP). 2. When administered electrophoretically to rat spinal neurones in vivo, these compounds were found to be selective NMDA antagonists with little effect on excitations evoked by quisqualate and kainate. CPMP and CPPP were approximately equipotent with CPP and about 5 times more potent than D-AP5. 3. Following systemic administration, 2-5 mg kg-1 i.v. of CPP, CPMP and CPPP reduced NMDA-evoked excitations by 70-100% whereas 50-100 mg kg-1 of D-AP5 and DL-AP7 produced a similar effect. The onset of the effects required 20-30 min and lasted more than six hours. 4. On bath application to cortical wedges, the IC50 values (microM) for antagonism of 40 microM NMDA were: CPP, 0.64 +/- 0.06 (mean +/- s.e.mean; n greater than 4); CPMP, 1.65 +/- 0.13; CPPP 0.89 +/- 0.09; D-AP5, 3.7 +/- 0.32; DL-AP7, 11.1 +/- 2.1; and DL-AP4 and DL-AP6 were inactive at 100 microM. 5. In binding studies with [3H] CPP, the Ki values (nM) were: CPP, 446 + 150 (mean + s.e.mean; n > 3); CPMP, 183 + 74 and CPPP, 179 +/- 13 whereas against NMDA (lO microM)-stimulated [3H]- TCP (thienylcyclohexylpiperidine) binding the ICjo values (microM) for CPMP and CPPP respectively were 5.6 + 2.7 and 4.5 + 2.2. 6. Systemic administration of CPPP and CPMP, at doses sufficient to antagonize NMDA, also reduced cardiovascular responses to 5-hydroxytryptamine (Bezold-Jarisch reflex). This illustrates a role for NMDA receptors in central cardiovascular control. 7. The results indicate the systemic doses of piperidine and piperazine analogues of D-AP5 which may be used for assessing the role ofNMDA receptors in central synaptic function. PMID- 2905187 TI - Comparison of a low molecular weight heparin and unfractionated heparin for the prevention of deep vein thrombosis in patients undergoing abdominal surgery. The European Fraxiparin Study (EFS) Group. AB - In a prospective, randomized multicentre trial the efficacy and safety of the low molecular weight heparin (LMWH) fraction Fraxiparin and unfractionated calcium heparin (Calciparin) were compared for the prevention of postoperative deep vein thrombosis. Of 1909 patients included in the trial 1896 underwent abdominal surgery and received either one daily subcutaneous injection of 7500 anti-Xa units Fraxiparin or 5000 units calcium heparin three times a day subcutaneously. Elastic compression stockings were worn by both groups of patients in the postoperative period. Before randomization the patients were stratified in two subgroups with or without malignant disease. To assess the rate of deep vein thrombosis (DVT), 125I-labelled fibrinogen leg scanning was performed daily for 7 postoperative days. Positive results were confirmed by phlebography whenever possible. Venous thrombosis occurred in 27 of 960 patients (2.8 per cent) given Fraxiparin and in 42 of 936 patients (4.5 per cent) given calcium heparin (P = 0.034). The rates of proximal vein thrombosis were 0.4 per cent (4 patients) and 1.4 per cent (13 patients) respectively (P less than 0.05). Pulmonary embolism occurred in 2 of 960 patients (0.2 per cent) treated with Fraxiparin and in 5 of 936 patients (0.5 per cent) treated with calcium heparin. The two treatments were equally well tolerated. Intra- and postoperative blood loss, the number of wound haematomas as well as frequency and volume of transfusions were similar in both groups. The present trial demonstrates that a single daily subcutaneous injection of Fraxiparin is more effective than the established low dose subcutaneous heparin prophylaxis with 5000 units three times per day in preventing postoperative DVT after abdominal surgery in patients wearing compression stockings. PMID- 2905188 TI - Adjuvant treatments following curative resection for gastric cancer. The Italian Gastrointestinal Tumor Study Group. AB - The results of a prospective randomized trial of adjuvant treatment after curative resection for gastric cancer are reported. The study consisted of three arms: (1) surgery only; (2) chemotherapy (5-fluorouracil (FU) and 1-(2 chloroethyl)-3-(4-methylcyclohexil)-1-nitrosourea (Me-CCNU] after surgery; (3) chemo-immunotherapy (FU, Me-CCNU and levamisole) after surgery. Between March 1977 and June 1981, 235 patients were included in the study by 18 co-operating institutions. Thirteen per cent of patients in arm 2 and thirteen per cent in arm 3 suffered major toxicity, necessitating interruption of treatment. Two of these patients died of marrow aplasia. Statistical analysis of survival showed that prognosis was influenced by the well-known prognostic variables, invasion of the wall, nodal status and site of tumour. The different treatments in the three arms, however, did not show any impact on prognosis, even when adjustments were made for the most relevant prognostic variables. Given the lack of effect on survival and the presence of clinically important toxicity, FU and Me-CCNU +/- levamisole cannot be recommended as adjuvant therapy for resected gastric cancer. PMID- 2905189 TI - Sex differences in nuclear androgen receptors in guinea pig brain and the effects of an alpha 2 noradrenergic blocker on androgen receptors. AB - The binding of the synthetic androgen, [3H]methyltrienolone (R1881) to nuclear androgen receptors (NAR) was studied in various brain areas of gonadectomized male and female guinea pigs treated for 3 days with 2 mg testosterone propionate. The Scatchard analysis of salt-extracted NAR showed a single, high-affinity receptor with a Kd of 0.152 nM and maximum binding sites (Bmax) of 161.9 fmol/mg DNA. The concentration of NAR was highest in the hypothalamus (HYPO) and preoptic area (POA) in both males and females. Lower receptor levels were detected in the amygdala and cortex. NAR levels were significantly lower in the POA of females than in males. Systemic injection of prazosin, an alpha 1-adrenergic antagonist had no effect on NAR concentrations, but an alpha 2-antagonist, idazoxan, significantly reduced the binding of [3H]R1881 to NAR in both HYPO and POA. The reduction in binding of the ligand to receptor was not due to alterations in affinity of NAR, but rather to the decline in the number of receptors. PMID- 2905190 TI - Evidence that adenosine A2 and dopamine autoreceptors antagonistically regulate tyrosine hydroxylase activity in rat striatal synaptosomes. AB - Incubation of rat striatal synaptosomes with the adenosine receptor agonist 2 chloroadenosine (2-CADO) produced a concentration-dependent increase of dopamine (DA) synthesis (about 50% of control value). The effect was not additive with the stimulation produced by either 10 microM forskolin or 2 mM dibutyryl cyclic AMP. Pretreatment of striatal synaptosomes with 2-CADO produced an activation of tyrosine hydroxylase (TH) which withstood washing and lysing of the tissue. This activation was largely independent of the presence of Ca2+ ion in the preincubation medium and, when analyzed as a function of different concentrations of the pterin cofactor 6-methyl-5,6,7,8-tetrahydropterin (0.08-0.4 mM), it was associated with an apparent increase in the Vmax of the enzyme. Quinpirole, a selective D2 DA receptor agonist, reduced control synaptosomal DA synthesis and caused a persistent inhibition of TH activity. When added together with 2-CADO, quinpirole depressed the stimulation of DA synthesis and TH activity produced by the adenosine analog. The effect of quinpirole was stereospecifically antagonized by the D2 DA antagonist sulpiride. Quinpirole also inhibited the activation of TH elicited by a submaximal concentration of forskolin, but not that produced by dibutyryl cyclic AMP. The inhibitory effect of quinpirole on basal and 2-CADO stimulated TH activities was mimicked by DA. These results indicate that presynaptic DA autoreceptors and adenosine A2 receptors interact antagonistically in controlling DA synthesis in rat striatal synaptosomes presumably by exerting opposite inputs on a presynaptic adenylate cyclase system. PMID- 2905191 TI - Excitatory amino acid receptors intrinsic to synaptic transmission in nucleus tractus solitarii. AB - Excitatory amino acid (EAA) receptors are present in the nucleus tractus solitarii (NTS), and there is growing evidence that L-glutamate (L-Glu) may activate neurons in this region to precipitate changes in autonomic discharge. To evaluate the potential role of EAA agonists in synaptic transmission in NTS, we studied the responses of single units in an in vitro brain slice preparation of NTS to electrical stimulation of one or both solitary tracts (TS) before, during and after superfusion with selected EAA antagonists. Dose-response studies demonstrated that the synaptic input to NTS units was substantially blocked by 2 amino-5-phosphonovaleric acid (APV) at perfusion concentrations of 1 mM, by kynurenic acid (KYN) at 10 mM, and glutamate diethylester (GDEE) at 10 mM. Using these concentrations, we examined the responses of single NTS neurons to afferent input from ipsilateral and contralateral TS stimulation before, during and after perfusion with each antagonist. KYN inhibited afferent input from one TS but not the other in 7 of 13 cells tested, inhibited both inputs in 4, and caused differential augmentation of input in two. APV caused differential inhibition of the two inputs in 4 of 9 cells tested, differential excitation in 1 and inhibition of both inputs in one. GDEE caused differential inhibition in 4 of 9 cells tested, differential excitation in 3 and inhibition of both inputs in one. When inputs from a single TS were examined, those blocked by APV were always blocked by KYN (5 of 16 inputs tested); there was overlap between the blocking effects of KYN and GDEE (4 of 12 inputs tested) and occasionally of APV and GDEE (one of 12 inputs tested). We also observed differential blocking effects of these agents on single inputs to the same neuron. Evoked responses were reduced or enhanced by only one of the two agents for 5 of 16 inputs tested with KYN and APV, 4 of 12 tested with KYN and GDEE, and 7 of 12 tested with APV and GDEE. The average reduction in synaptically evoked responses caused by blocking doses of antagonist was 85 +/- 6% for KYN, 63 +/- 28% for APV and 68 +/- 10% for GDEE. These data indicate that all 3 major EAA antagonists can selectively inhibit electrically evoked afferent input to NTS neurons and suggest a role for specific EAA receptors in mediating input to these neurons over different afferent pathways. PMID- 2905192 TI - NMDA receptor blockade prevents the increase in protein kinase C substrate (protein F1) phosphorylation produced by long-term potentiation. AB - Recent evidence has implicated activation of the N-methyl-D-aspartate (NMDA) class of glutamate receptor in the initiation of hippocampal long-term potentiation (LTP), an electrophysiological model of information storage in the brain. A separate line of evidence has suggested that activation of protein kinase C (PKC) and the consequent phosphorylation of its substrates is necessary for the maintenance of the LTP response. To determine if PKC activation is a consequence of NMDA receptor activation during LTP, we applied the NMDA receptor antagonist drug, DL-aminophosphonovalerate (APV) both immediately prior to and following high frequency stimulation, resulting in successful and unsuccessful blockade of LTP initiation, respectively. We then measured the phosphorylation of a PKC substrate (protein F1) in hippocampal tissue dissected from these animals. Only successful blockade of LTP initiation by prior application of APV was seen to block the LTP-associated increase in protein F1 phosphorylation measured in vitro (P less than 0.001 by ANOVA). This suggests that NMDA receptor-mediated initiation triggers maintenance processes that are, at least in part, mediated by protein F1 phosphorylation. These data provide the first evidence linking two mechanisms associated with LTP, NMDA receptor activation and PKC substrate phosphorylation. PMID- 2905193 TI - The effect of an uptake inhibitor (dihydrokainate) on endogenous excitatory amino acids in the lamprey spinal cord as revealed by microdialysis. AB - Microdialysis was utilized to test the effects of the uptake inhibitor dihydrokainate (DHK) on endogenous amino acid levels in the lamprey spinal cord in vitro. The level of L-glutamate increased markedly (165%) in the presence of DHK, whereas the level of the glutamate precursor L-glutamine decreased (53%). Since DHK can potentiate or evoke fictive locomotion in the lamprey spinal cord, it is suggested that L-glutamate is released by neurons which take part in the activation of the spinal locomotor network. PMID- 2905194 TI - Stretch-induced release of proctolin from the dendrites of a lobster sense organ. AB - Reversed-phase high-performance liquid chromatography coupled with a sensitive bioassay was used to quantify the content of proctolin in the peripheral sensory endings of a crustacean mechanoreceptor, the oval organ, and to examine for its release in response to the physiological stimulus of stretch. Material co-eluting with proctolin and showing proctolin-like bioactivity was present in the oval organ and in the nerve trunks containing the 3 sensory axons. Repetitive stretch stimulation, in which the dendrites were exposed to physiological stretch amplitudes, resulted in a significant increase in the release of proctolin from the oval organ in vitro. Approximately 11.7% of the total proctolin stored in the oval organ was released during a 5 min stimulation period. The stretch-evoked release of proctolin was calcium dependent. Since a previous study has shown that proctolin has excitatory effects upon these primary afferents, the present results imply that endogenous proctolin may function to self-modulate the sensory transduction mechanism of these sensory terminals. PMID- 2905195 TI - L-glutamate stimulation of the zona incerta in the rat decreases heart rate and blood pressure. AB - Microinjections of L-glutamate into the zona incerta of pentobarbital anesthetized rats caused decreases in blood pressure and heart rate. The bradycardic response was reduced by approximately 70% after i.v. administration of atropine methyl nitrate. After combined muscarinic and beta-adrenergic blockade the bradycardic response was reduced to 90% of the control value. This suggests that the bradycardia was mediated primarily by activating the vagal outflow. Blood pressure decreases elicited after pharmacological blockade of the heart with both atropine and timolol were approximately 50% of the control values. This indicates that the zona incerta is also capable of altering stroke volume and/or inhibiting the sympathetic outflow controlling the peripheral blood vessels. By using an injectate containing L-glutamate mixed with [3H]L-glutamate and subsequent analysis of autoradiographic tissue sections, we have determined that the most reactive site is the region of the ventral zona incerta. PMID- 2905196 TI - Diazepam attenuation of somatostatin-induced motor disturbances and neurotoxicity. AB - Intracerebroventricular somatostatin administration to conscious rats results in a characteristic motor abnormality (barrel rotation), convulsions that are frequently fatal and destruction of cerebellar Purkinje cells. This study demonstrates that each of these manifestations of this neuropeptide can be attenuated by pretreatment with diazepam (Valium, 5 mg/kg, i.p.) but not in vehicle-pretreated controls. Specifically, the incidence of mortality was reduced from 5/12 controls to 2/20 diazepam-treated rats, the incidence of barrel rotation was reduced from 6/12 controls to 2/20 diazepam-treated rats and the incidence of Purkinje cell death was reduced from 4/4 examined controls to 4/13 diazepam-treated animals. Vehicle pretreated rats did not differ from untreated rats. Thus, in addition to blocking somatostatin-induced motor dysfunction and mortality, diazepam offers significant protection from central neuronal cell death in the cerebellar cortex. PMID- 2905197 TI - Neurotoxic lesions of the dorsolateral pontomesencephalic tegmentum-cholinergic cell area in the cat. II. Effects upon sleep-waking states. AB - Kainic acid was injected bilaterally (4.8 micrograms in 1.2 microliters each side) into the dorsolateral pontomesencephalic tegmentum of cats in order to destroy the cholinergic neurons located in that region and thus to study the effects of their destruction upon sleep-waking states. The kainic acid produced a large area of nerve cell loss and/or gliosis centered in the dorsolateral tegmentum-cholinergic cell area, that includes the pedunculopontine tegmental (PPT) and laterodorsal tegmental (LDT) nuclei rostrally (A1-P2), and the parabrachial (PB) and locus coeruleus (LC) nuclei caudally (P3-P5). The mean loss of choline acetyltransferase (ChAT)-immunoreactive neurons within this area was 60% with a range from 25% to 85% across 11 cats. The mean loss of tyrosine hydroxylase (TH)-immunoreactive neurons, differentially distributed through the same region, was 35% with a range of 0-50%. Whereas the kainic acid lesions appeared to have only slight effects upon wakefulness and slow-wave sleep, they had marked effects upon paradoxical sleep (PS), which varied in degree across animals. In cats with the most extensive destruction of cholinergic neurons, PS was eliminated in the first few weeks following the lesion and then reappeared as isolated episodes characterized by sparse, low amplitude PGO spikes in association with few eye movements and an activated cortex, though in absence of neck muscle atonia. Although these PS-like episodes varied in amount, they were significantly less than baseline PS in percent and in duration for the group of 11 animals over one month recording. The PGO spike rate was significantly reduced; the EMG amplitude was significantly increased, marking a loss of neck muscle atonia. The percent of PS-like epochs, the rate of PGO spiking and the EMG amplitude on postlesion day 28 were found to be significantly correlated with the volume of the lesion within the dorsolateral pontine tegmentum-cholinergic cell area. The percent PS-like episodes and PGO spike rate were significantly correlated with the number of remaining ChAT-immunoreactive neurons, but not with the number of remaining TH-immunoreactive neurons within this region. These results suggest that cholinergic pontomesencephalic neurons may be critically involved in the generation of paradoxical sleep and its phasic events. PMID- 2905198 TI - Effects of chronic experimental streptozotocin-induced diabetes on the noradrenergic and peptidergic innervation of the rat alimentary tract. AB - Immunohistologic localization of tyrosine hydroxylase (TOH), dopamine-beta hydroxylase (DBH) and selected neuropeptides (vasoactive intestinal polypeptide, gastrin-releasing peptide (GRP)/bombesin, substance P, Leu-enkephalin, Met enkephalin, dynorphin B, neuropeptide Y (NPY), somatostatin) was used to investigate the innervation of the small bowel in a rat model of diabetic autonomic neuropathy. Paravascular mesenteric nerves (extrinsic) and intramural nerves of chronically (12-18 month) diabetic rats were characterized by the presence of numerous, markedly swollen dystrophic axons which stained intensely for TOH and DBH. The peptidergic complement of axons, however, showed no evidence of comparable dystrophic axonopathy. PMID- 2905199 TI - Immunocytochemical analysis of somatostatin in the hypothalamus of obese and non obese Zucker rats. AB - Levels of growth hormone (GH) are reduced in the genetically obese Zucker rat, fa/fa, in comparison to lean littermates. In normal rats, GH release is regulated by stimulatory and inhibitory factors of hypothalamic origin. The present experiment focuses on hypothalamic somatostatin (SOM; growth hormone release inhibiting factor) in order to determine if abnormal hypothalamic SOM may be a correlate of depressed GH secretion in fa/fa rats. We compared immunocytochemical localization of hypothalamic SOM between 5 obese (fa/fa) Zucker rats and 5 non obese littermates. Brain sections from pairs of animals were processed simultaneously. The distribution of SOM immunoreactive cell bodies in the hypothalamus agreed with previous reports. SOM-containing neurons in the periventricular area were counted and analyzed at 4 hypothalamic levels: (1) anterior to the suprachiasmatic nucleus (SCN); (2) through SCN; (3) between SCN and the ventromedial hypothalamic nucleus (VMH); and (4) through VMH. The greatest number of SOM-immunoreactive cell bodies was observed at levels (2) and (3). The numbers of SOM-containing cells did not differ significantly between obese and lean animals. No apparent difference in density of fiber staining was observed in the median eminence. PMID- 2905200 TI - Neuropeptide Y-immunoreactive neurons receive synaptic inputs from dopaminergic axon terminals in the rat neostriatum. AB - Double immunocytochemistry using peroxidase-antiperoxidase and protein A-gold was performed to determine whether neuropeptide Y (NPY) immunoreactive neurons receive synaptic inputs from catecholaminergic axon terminals in the rat neostriatum. Tyrosine hydroxylase-immunoreactive axons were found to be in synaptic contact with the somas and proximal dendrites of NPY-immunoreactive neostriatal neurons. These latter neurons were medium-sized and had indented nuclei, and thus were thought to be medium aspiny interneurons. Thus nigrostriatal dopaminergic neurons may monosynaptically influence striatal NPY neurons. PMID- 2905201 TI - Activation of protein kinase C induces a long-term depression of glutamate sensitivity of cerebellar Purkinje cells. An in vitro study. AB - In immature rat cerebellar slices in vitro, a long term depression (LTD) of the responses of Purkinje cells (PCs) to L-glutamate (Glu) was achieved in 30% of the recorded cells by simultaneous stimulation of the neurones by Glu and by climbing fibres (CFs). This effect was not observed for L-aspartate (Asp)-induced responses. Similarly, selective LTD of Glu-induced responses was obtained in 22% of the cells by pairing Glu applications with direct stimulation of the cells which elicited calcium spikes in these neurones. Finally, bath application of phorbol esters also induced a selective LTD of Glu-induced responses in all cells tested. These results suggest that protein kinase C is involved in cerebellar synaptic plasticity. PMID- 2905202 TI - Long-term potentiation in the dentate gyrus of the anaesthetized rat is accompanied by an increase in protein efflux into push-pull cannula perfusates. AB - Changes in protein content of push-pull cannula perfusates from the dentate gyrus of anaesthetized rats were analyzed before and after the induction of long-term potentiation (LTP). LTP, induced by either high-frequency stimulation of the perforant path or raising the extracellular calcium concentration, was associated with increases in the protein content of the perfusates. Tetanically induced LTP was accompanied with a large but delayed increase (apparent in the second hour after the stimulation) in protein efflux. In contrast, when LTP was induced by the elevation of extracellular calcium concentration, a smaller but more immediate increase in protein efflux was observed. When 5-D aminophosphonovalerate was used to block the induction of LTP, no increase was observed in either case. These results indicate that LTP in the dentate gyrus is accompanied by an increase in the efflux of proteins into push-pull cannula perfusates. The possible origins of these proteins and their role in LTP are discussed. PMID- 2905203 TI - MPTP produces a pattern of nigrostriatal degeneration which coincides with the mosaic organization of the caudate nucleus. AB - In the normal dog we have found that cholinesterase and tyrosine hydroxylase (TH) histochemistry define a mosaic structure of the caudate nucleus that is similar to that described in other species. To determine if nigrostriatal afferents interlocked with this mosaic we injected dogs with 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP), a toxin specific to dopaminergic nigrostriatal cells. Alternate sections in the caudate nucleus stained for acetylcholinesterase, TH, and terminal degeneration revealed that the areas of densest degeneration were localized to the matrix, thereby outlining areas of much lighter degeneration which were coincident with the patches. This pattern of terminal degeneration suggests the existence of subcomponents of the dopaminergic nigrostriatal pathway, at least one of which might be selectively vulnerable to MPTP. PMID- 2905204 TI - Expression of the homeobox gene, Hox 2.1, during mouse embryogenesis. AB - This article reviews recent studies on the expression of the homeobox gene, Hox 2.1, during mouse embryogenesis, using the technique of in situ hybridization. Differential hybridization of radiolabelled antisense versus sense strand RNA is first clearly detected in sections of 8.5 day post coitum (p.c.) early somite embryos. At 12.5 days p.c., higher levels of Hox 2.1 expression are seen in the spinal cord, extending into the base of the hind brain. Hybridization of antisense Hox 2.1 RNA is also seen in the spinal ganglia, in the nodose ganglia of the Xth cranial nerve (which contains derivatives of the neural crest arising from the posterior hind brain), and in the myenteric plexus. Mesodermal cells of certain visceral organs also express Hox 2.1 RNA, in particular the mesoderm of the lung, stomach and meso- and meta-nephric kidney. Comparison of the spatial domains of expression of mouse homeobox genes reveals a pattern consistent with the idea that they play a role in anteroposterior positional specification during embryogenesis. PMID- 2905205 TI - Normal and cryptorchid castration. AB - Surgical exploration of the horse that has presumably had a normal castration or a previously successful cryptorchid surgery remains a distinct challenge. No hard and fast rules dictate a proper course of action for each case. If a horse was anesthetized for routine castration, discovered to have only one scrotal testis, had a brief exploratory on the nondescended side and was recovered, trauma to the inguinal region would probably be sufficiently minimal that an inguinal approach could be used at subsequent exploratory surgery. If the inguinal canal was extensively manipulated and the tail of the epididymis was inadvertently removed, however, one of the alternate approaches would be advisable. Where previous history is unknown, external and rectal palpation, hormonal assays, and careful evaluation of the scrotal/inguinal scars under anesthesia are advisable prior to proceeding with a specific course of action. As previously cited, "one hopes for the best but prepares for the worst." Where inguinal canals are being explored in the supposedly previously castrated horse that still has aggressive male behavior, the surgeon is searching for vaginal process and contents or the stump of the spermatic cord. If the stump is identified to suggest complete previous castration, the stump should contain cremaster muscle, parietal vaginal tunic, testicular vessels, and ductus deferens. If a second nonvascular tubular structure is found but no testicular vessels are found, the tail of the epididymis was inadvertently removed and assumed to be hypoplastic testis. This determination can be difficult to make on gross observation of the stump. Again, a thorough case workup helps one plan in advance for what should be found at surgery. PMID- 2905206 TI - Production of pili on Vibrio parahaemolyticus. AB - Electron microscopic examination showed that all strains of Vibrio parahaemolyticus examined had pili on their surface when the organism was grown on marine agar at 28 degrees C for 6-12 h. The pili were morphologically stable on heat treatment at 60 degrees C for 10 min, but both the lateral and polar flagella possessed by this organism were labile. No immunological cross reactivity between pili of enterotoxigenic Escherichia coli and Vibrio cholerae non-01 and those of V. parahaemolyticus was observed. PMID- 2905207 TI - Successful propranolol therapy for neuroleptic-induced akathisia resistant to anticholinergic and benzodiazepine drugs. PMID- 2905208 TI - Neuroleptic malignant syndrome. The results of a 6-month prospective study of incidence in a state psychiatric hospital. PMID- 2905209 TI - Characterization of gliding motility in Flexibacter polymorphus. AB - Motility of the marine gliding bacterium Flexibacter polymorphus was studied by using microcinematographic techniques. Following adhesion to a glass surface, multicellular filaments and individual cells usually began to glide within a few seconds at a speed of approximately 12 micron per second (at 23 degrees C). Adhesion to the glass surface was evidently mediated by multitudes of extremely fine extracellular fibrils. Gliding velocity was independent of filament length but directly related to electron-transport activity and substratum temperature in the range 3-35 degrees C. The rate of gliding was inversely related to medium viscosity, suggesting that the locomotor apparatus functions at constant torque. Forward motion was occasionally interrupted by direction reversals, somersaults (observed primarily in single cells of short filaments), or spinning of filaments tethered by one pole. The frequency of direction reversal was found to be an inverse function of filament length. Translational motility was invariably accompanied by sinistral revolution about the longitudinal axis of a filament. The sense and pitch of revolution were constant among filaments of different length. Polystyrene microspheres or India ink particles adsorbed to gliding cells were actively displaced in either direction, their movement tracing either a regular zigzag or helical path along the filament surface. Because microspheres were also observed to move on nonmotile filaments, particle translocation was evidently not obligatorily linked to gliding locomotion. Multiple particles adsorbed to a single filament often moved independently. The data are consistent with a motility mechanism involving limited motion in numerous mechanically independent (yet functionally coordinated) domains on the cell surface. PMID- 2905210 TI - [DNA analysis as a method for the prevention of cystic fibrosis]. PMID- 2905211 TI - [Effect of a tablet to prevent epidemic hemorrhagic fever on immunologic function and plasma cyclic nucleotides]. PMID- 2905212 TI - Analogs of unusual sponge phospholipids. Synthesis and thermotropic properties of 1,2-di-(6Z,9Z)-6,9-hexacosadienoyl phosphatidylcholine and phosphatidylethanolamine. AB - The major marine sponge phospholipids 1,2-di-(5Z,9Z)-5,9-hexacosadienoyl phosphatidylcholine (PC) and phosphatidyl-ethanolamine (PE) hardly incorporate cholesterol into their liposomal bilayers, as reported earlier. Our previous studies indicated that their synthetic short chain (C18-C24) analogs with the same double bond pattern readily incorporated cholesterol, thus demonstrating the importance of the chain length. In order to investigate the possible role of the unusual delta 5,9 diunsaturation 1,2-di-(6Z,9Z)-6,9-hexacosadienoyl phosphatidylcholine and phosphatidylethanolamine were synthesized and their thermotropic behavior studied. Both analogs shows a transition endoterm at 45 degrees C, while the natural 1,2-di-(5Z,9Z)-5,9-hexacosadienoyl PC and its PE counterpart exhibited it at 42 degrees C. A partial incorporation of cholesterol into liposomal bilayers of 1,2-di-(6Z,9Z)-6,9-hexacosadienoyl PC was observed. Our results suggest that while the chain length is the predominant factor in the interactions of these phospholipids with sterols, the double bond location may also play a contributing role. PMID- 2905213 TI - Influence of hyperglycemia on glucose uptake and hepatic glucose production in non-dialyzed uremic patients. AB - To determine whether the deranged glucose metabolism in uremia, in addition to insulin resistance can be attributed also to reduced glucose-induced glucose uptake, a two-step sequential hyperglycemic clamp (plasma glucose: 120 and 300 mg/dl) was performed in 6 non-dialyzed uremic and 8 healthy subjects. A constant infusion of somatostatin (300 micrograms/h) and soluble insulin (0.2 mU/kg/min) resulted in peripheral serum insulin slightly higher than basal in both uremics (16 +/- 3 and 22 +/- 3 microU/ml; step 1 and 2, respectively) and controls (20 +/ 2 and 22 +/- 1 microU/ml). The glucose-induced glucose uptake (3-3H-glucose) assessed as the difference between step 2 and 1 glucose disposal at the final 30 min of each step was markedly reduced in uremics (3.2 +/- 0.5 mg/kg/min) compared to healthy subjects (5.7 +/- 0.8 mg/kg/min; p less than 0.03). However, the percentage increment in glucose uptake from step 1 to step 2 hyperglycemia was comparable in the two groups (134 +/- 27 and 148 +/- 17%). Modest hyperglycemia (120 mg/dl) and slightly raised insulinemia resulted in comparable suppression of the endogenous (hepatic) glucose production (EGP) in healthy (1.6 +/- 0.2 mg/kg/min) and uremic subjects (1.5 +/- 0.3 mg/kg/min). In controls, pronounced hyperglycemia (300 mg/dl) further reduced EGP (0.6 +/- 0.3 mg/kg/min; p less than 0.01) while EGP in uremics on the contrary tended to rise (2.0 +/- 0.4 mg/kg/min; p = 0.09), thus indicating an abnormal reaction of the liver.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2905214 TI - Multiple endocrine neoplasia (MEN) type II b: report of a case observed at autopsy with immunohistochemical study of mucosal neuromas. AB - A case of multiple endocrine neoplasia (MEN) II b syndrome was studied in a 28 year-old Colombian woman. The patient presented initially with medullary carcinoma of the thyroid (MTC), an unusual habitus, numerous mucosal neuromas, and intestinal ganglioneuromatosis. Recurrent medullary carcinoma in the mediastinum produced compression. The tumor mass could not be removed surgically, and the patient died of post-operative complications. At autopsy metastatic MTC was present in the liver, lymph nodes, and lungs. In addition, multiple mucosal neuromas were present in the mouth, nasopharynx, larynx, digestive tract, peri adrenal fat, and hepatic portal spaces. There was no evidence of pheochromocytoma. Immunofluorescence study of mucosal neuromas showed hyperplasia and hypertrophy of nerves, without evidence of tumor. Kindred screening was negative. PMID- 2905215 TI - Treatment of acute agitation in the elderly. PMID- 2905216 TI - Immunoglobulin heavy chain switch region polymorphisms are not associated with type 1 diabetes. AB - In order to ascertain whether the immunoglobulin heavy chain genes are important in the aetiology of Type 1 diabetes, we have used restriction fragment length polymorphism (RFLP) analysis of genomic DNA to study 148 Caucasoid subjects with Type 1 diabetes and 146 normal Caucasoid subjects. A DNA probe homologous to the switch regions for the IgM (S mu) and IgA1 (S alpha 1) genes when used in conjunction with the restriction endonuclease Sst I detects RFLPs at both these loci. There were no significant differences in phenotype or gene frequencies for the alleles of S mu or S alpha 1 in the patients when compared with control subjects; nor were there significant associations of S mu or S alpha 1 with HLA DR type or gender. PMID- 2905217 TI - HLA-D region RFLP and type 1 diabetes. PMID- 2905218 TI - Special issue dedicated to John H. Welsh on the occasion of his 85th birthday. PMID- 2905219 TI - Special cellular and synaptic mechanisms in motor pattern generation. PMID- 2905220 TI - Photobehavior of marine invertebrates: extraocular photoreception. PMID- 2905222 TI - Serotonin: history of a discovery. PMID- 2905221 TI - Studies on the crustacean cardiac ganglion. AB - 1. An overview of studies on the decapod crustacean cardiac ganglion is given emphasizing contributions to questions of general interest in cellular neurophysiology. 2. John Welsh, in 1951, introduced this 9-celled, semi autonomous ganglion as a preparation offering physiologists unique experimental possibilities. 3. It exhibits remarkable reliability and stability in rhythmic pattern generation. The neurons show endogenous burst-forming capability mediated by "driver potentials". 4. These regenerative, Ca-mediated potentials are restricted to the soma, while impulse-generating membrane is segregated to the distal axon. 5. Thus, voltage-clamp analysis of the ionic currents underlying the burst-forming potentials is possible by isolating the soma with a ligature. 6. The isolated ganglion is spontaneously active, but the normal mechanism of pacemaking remains to be clarified, including the possible contribution of stretch-sensitive dendrites. 7. The activity of the ganglion is subject to modulation by neurohumors. These include the transmitter at intraganglionic synapses, transmitters of the pair of inhibitory and the two pairs of acceleratory fibers, and neurohormones released from the pericardial organs. The transmitters are not established. 8. Effects on the ganglion of substances isolated from the pericardial organs have been described. 9. These include 5 hydroxytryptamine, dopamine, octopamine, and two peptides. 10. One of these, proctolin, produces a long-lasting sequence of effects. 11. The work continues to raise new questions for which the ganglion offers excellent research material. PMID- 2905223 TI - Acetylcholine suppresses calcium current in neurons of Aplysia californica. AB - 1. The left upper quadrant neurons L2-L6 in the abdominal ganglion of Aplysia californica were voltage clamped in order to examine effects of acetylcholine on voltage-dependent Ca and Ca-dependent K currents. 2. "Puffed" application of 10 100 microM acetylcholine reduced both the early inward and late outward phases of the current elicited by depolarizing voltage steps. An identical effect of the peptide FMRFamide was previously found to result from a suppression of the Ca and Ca-dependent K currents. 3. This effect of acetylcholine was obscured by the simultaneous activation of a previously described K current resembling the "S" current. Extracellular tetraethylammonium (TEA) and 4-aminopyridine could not be used to eliminate this current, because both compounds also appeared to block the acetylcholine receptor mediating the putative suppression of Ca and Ca-dependent K currents. 4. The acetylcholine-induced "S"-like and other K currents could, however, be reduced or eliminated by injection of TEA+ or Cs+ into the cell, replacement of extracellular Ca2+ with Ba2+, and by shifting the K+ equilibrium potential so as to null K currents at the potential used to record Ca current, revealing in each case a partial (10-40%) suppression of the Ca (or Ba) current by acetylcholine. 5. The reduction of the outward phase of depolarization activated current was confirmed to represent suppression of the Ca-dependent K current by acetylcholine. This effect was indirect, secondary to the suppression of Ca current, since acetylcholine had no effect on Ca-dependent K current elicited by direct injection of Ca2+ into the cell. 6. Activation of the "S"-like K current and suppression of the Ca current by FMRFamide are likely to be important in its proposed role as an agent of presynaptic inhibition in Aplysia. Since acetylcholine has identical effects, it too may have such a function. PMID- 2905224 TI - Circadian rhythms in adaptation to light of Limulus photoreception. AB - 1. The lateral eye of Limulus responds differently to light-adaptation depending upon whether the eye is tested during the day, or at night when a central circadian clock is known to activate efferent fibers that terminate in the retina. 2. At night, the decrement in retinal sensitivity due to light-adaptation is less pronounced immediately following a light-flash but is greater at longer times after the flash when compared with responses recorded during the day. 3. In our quantitative description of dark adaptation we find that at least two time constants are needed to describe the time course, and that the two decaying exponentials are differentially altered by circadian clock action. 4. We relate these day-to-night alterations in light-adaptive properties to circadian changes in physiology and morphology studied previously in Limulus photoreceptors. PMID- 2905225 TI - Postsynaptic modulation of cholinergic transmission by endogenous substances. AB - 1. Recent concept of postsynaptic modulation is reviewed on the basis of literature data and the results of our investigation using conventional intracellular and voltage-clamp recording methods, in vitro. 2. Experimental evidence provided that the sensitivity of nicotinic ACh receptors endowed on the postsynaptic membrane of the bullfrog sympathetic ganglia and of the frog skeletal muscle end-plate is either facilitated or inhibited by other neurotransmitters or neurohormones. 3. We propose that one neurotransmitter not only initiates its own postsynaptic potential but also regulates the efficacy of synaptic transmission mediated by a distinct neurotransmitter, as an endogenous "antagonist" or "sensitizer". PMID- 2905226 TI - Cephalopods, memory, neurofilaments, mammalian hibernation, the vertebrate retina: an autobiographical research note for John H. Welsh in his 85th year. PMID- 2905227 TI - Serotonin as a neurotransmitter: a review. PMID- 2905228 TI - New perspectives on catch. PMID- 2905229 TI - Russell's viper venom proteins: molecular probes for neurotransmitter receptors: a review. PMID- 2905230 TI - John Henry Welsh: his years, works and flock. AB - John H. Welsh came down from Boothbay, Maine in the late twenties and landed at Harvard. There he launched his academic career, raised a family, raised an additional family of graduate students and postdoctoral associates, and (with them all) shaped and cultivated diurnal rhythmicity, the biology of neurosecretion, and comparative neuropharmacology. After about 45 yr in the vineyards of Cambridge, he returned to Boothbay and his garden, tree-farm, grandchildren, writings and other good works. PMID- 2905231 TI - Serological diagnosis of jellyfish envenomations. AB - 1. A good correlation between the clinical and serological identification of envenomating jellyfish could be made on 30 healthy individuals and 74 patients stung by known species. 2. Six patients and one previous case were known to be false positive reactors. 3. Two of these individuals had dermatitis, one was asthmatic, three had previous significant hymenoptera envenomations and one was apparently normal. 4. Specific anti-jellyfish IgG serum concentrations would appear a few days after envenomation and persist for many months, even at high concentrations. 5. Significant numbers of patients exhibited cross reacting antibodies to other jellyfish, but no consistent pattern could be detected. 6. Significant titers were defined as those whose sera was positive after being be diluted 50-fold or greater. 7. Species specific IgM concentrations were regarded as significant only if their sera could be adsorbed against the homologous jellyfish antigen and the difference between adsorbed and non-adsorbed sera which were still positive was 50-fold. 8. Elevated persistent specific anti-jellyfish serum IgG concentrations which were still reactive if diluted 3000-fold were not protective against the cutaneous pain resulting from a natural sting. PMID- 2905232 TI - Mathematical model of cardiac mechanogram rhythmicity (based on mollusc heart). AB - 1. The time course of force development by the heart is modelled by Gompertz kinetics from the product of two terms: a cumulative increase in relative number of activated "contractile units", and an exponential decrease in contractile force. 2. For each beat, an "initial condition" is specified by an "intrinsic tension" parameter, and a specific rate of change of tension; cardioactive agents change these specifications. 3. Depending on parameter values, heartbeats are predicted that are constant, or in which the frequency, amplitude and baseline tension are appropriate to inhibited or augmented cardiac activity. PMID- 2905233 TI - [Evaluation of digital subtraction angiography (DSA) in the diagnosis of aorto arteritis]. PMID- 2905234 TI - [Peripheral neuropathy associated with polyarteritis nodosa: report of the clinical manifestations and pathologic findings of sural nerve biopsy in 21 cases]. PMID- 2905236 TI - Symposium on roxatidine acetate. Rottach-Egern, 3-5 June 1987. Proceedings. PMID- 2905235 TI - Effects of antibiotics on RNA polymerase III transcription. AB - We investigated the effects of six drugs on an RNA polymerase III in vitro transcription system. Adriamycin, daunorubicin, heparin, rifamycin AF/013, streptolydigin, and streptovaricin all inhibit RNA synthesis from a tRNA gene or the adenovirus 2 (AD2) VA1 RNA gene. The completed RNA polymerase III transcription complex is formed by the sequential, ordered addition of protein factors. Although both genes reportedly use the same transcription fractions for in vitro RNA synthesis, some of these drugs interfere differentially with these genes. A drug concentration that inhibits transcription from one gene may not inhibit transcription from the other gene. Adriamycin seems to block transcription if added between the binding of the individual transcription fractions. Daunorubicin appears to inhibit VA transcription only if added prior to both transcription fractions, but inhibits tRNA synthesis before and during transcription factor binding. Heparin blocks both genes between factors binding to DNA and after factor binding. Rifamycin blocks VA synthesis more effectively than tRNA synthesis. Streptolydigin blocks transcription of both genes. Streptovaricin probably blocks transcription by inhibiting early transcription complex assembly events. These drugs appear useful as appropriate probes to investigate transcription complexes since several discriminate between complexes formed on different genes during the assembly process. PMID- 2905237 TI - Prostaglandins, H2-receptor antagonists and peptic ulcer disease. AB - Peptic ulcer develops when offensive factors overwhelm defensive processes in the gastroduodenal mucosa. Offensive factors include NSAIDs, hydrochloric acid-peptic activity, bile reflux, and some products of the lipoxygenase pathway such as leukotriene B4; whereas defensive processes are largely mediated by prostaglandins through poorly understood mechanisms uniformly termed cytoprotection. Cytoprotection, a physiological process working through the products of arachidonic acid metabolism, may result from the net effect of the protective actions of prostaglandins versus the damaging actions of leukotrienes. Some prostaglandins also have antisecretory effects. Therefore the peptic ulcer healing effects of prostaglandin analogues, all of which have significant antisecretory activity, may be more due to their antisecretory effects than primarily to their effects on mucosal defences. Certain drug-induced gastroduodenal lesions, e.g. NSAID-induced ulcers, which are often unresponsive to H2-receptor antagonists, have been healed and their recurrence prevented by the use of PGE1 and PGE2 analogues. All the prostaglandin analogues investigated to date in humans have the potential for inducing abortion, an important side effect which may limit their worldwide use. The optimal prostaglandin analogue for ulcer healing should not induce abortion and should be potently cytoprotective. The predominant damaging agent in the development of peptic ulcer disease is gastric hydrochloric acid. Thus, the worldwide established efficacy and safety of H2-receptor antagonists such as cimetidine, ranitidine, famotidine and most recently of roxatidine acetate suggest that these agents have become the standard by which other forms of anti-ulcer therapy should be judged. PMID- 2905238 TI - Roxatidine acetate in the long term maintenance of duodenal ulcers. AB - A non-comparative multicentre study of 105 patients with healed duodenal ulcers was conducted to determine the effect on ulcer recurrence of 6 months' maintenance treatment with roxatidine acetate 75 mg daily. All patients had previously received roxatidine acetate treatment. 31 patients out of 89 had 32 relapsed ulcers after 6 months of treatment, which represents an overall relapse rate of around 30%; the relapse rate in smokers was double that of non-smokers. The overall incidence of epigastric pain did not increase significantly over the period of the trial, although some patients complained of mild pain when they entered the study despite having endoscopically confirmed healed ulcers. At the end of the study continuous poor appetite and pyrosis were reported by 17% and 6% of patients, respectively. Side effects, which included constipation and diarrhoea, were reported by 4 patients, 1 of whom withdrew from therapy. There were no clinically significant changes in laboratory values. Thus, maintenance treatment with roxatidine acetate 75 mg daily proved a safe and effective method of preventing symptomatic duodenal ulcer relapse. PMID- 2905239 TI - Clinical studies on the use of roxatidine acetate for the treatment of peptic ulcer in Japan. AB - Roxatidine acetate is a novel H2-receptor antagonist with a chemical structure different to the earlier drugs of this type. It is a potent inhibitor of histamine-mediated gastric acid secretion and in animal models is 4 to 6 times as potent as cimetidine. In a multicentre double-blind clinical trial of over 700 patients with gastric or duodenal ulcers roxatidine acetate 75 mg twice daily and cimetidine 200mg four times daily produced endoscopically confirmed and subjective and objective healing rates in excess of 90% for both types of ulcer, with no significant difference between the treatments. Roxatidine acetate's efficacy in stomal ulcer (marginal ulcer) and reflux oesophagitis has been confirmed in non-comparative studies of up to 8 weeks' duration. The overall incidence of adverse reactions in 1623 patients treated with roxatidine acetate 75 mg twice daily was 1.7%, with skin rashes and constipation the most frequently reported side effects. PMID- 2905240 TI - A comparison of roxatidine acetate and ranitidine in gastric ulcer healing. AB - A randomised multicentre double-blind study was conducted to compare the efficacy and safety of roxatidine acetate 75 mg twice daily and ranitidine 150 mg twice daily in 295 patients with endoscopically confirmed gastric ulcers. Substantial reductions in ulcer diameters and healing rates of 85.6 and 88.2% for roxatidine acetate and ranitidine, respectively, were obtained after 8 weeks of treatment. There was no difference in healing rates between smokers and non-smokers in either group. The relief of day and night-time epigastric pain was comparable for both treatment groups, as was antacid tablet consumption, with the majority of patients pain-free at the end of the study. The incidence of side effects was low, with 3 patients treated with roxatidine acetate, compared with 4 ranitidine treated patients, reporting adverse reactions. There were no clinically significant changes in laboratory values. The present study suggests that 8 weeks of treatment with roxatidine acetate 75 mg twice a day produces effective and safe acute management of gastric ulcers which is comparable to that seen with ranitidine. PMID- 2905241 TI - A comparison of roxatidine acetate 150 mg once daily and 75 mg twice daily in gastric ulcer healing. AB - In 363 outpatients with endoscopically confirmed gastric ulcers the efficacy and safety of roxatidine acetate 150 mg at night was compared to 75 mg twice daily. After 8 weeks' treatment substantial reductions in gastric ulcer diameter were obtained in addition to healing rates of 83.7 and 86% for the twice daily and night-time dosing, respectively. Daily reductions in day and night-time epigastric pain were obtained with no significant differences between treatment groups for pain scores or antacid tablet consumption. Furthermore, cigarette smoking did not influence the healing rates produced by either treatment schedule. 26 patients reported 32 adverse reactions and 5 patients discontinued treatment because of side effects, although only 1 of these was a severe reaction. The present data suggest that a single night-time dose of roxatidine acetate 150 mg is as safe and effective as the twice daily dose regimen for the management of acute gastric ulceration. PMID- 2905243 TI - Appendix 1. Therapeutic resistance of peptic ulcers. PMID- 2905242 TI - Roxatidine acetate in the long term maintenance of gastric ulcers. AB - A non-comparative multicentre study of 78 patients with healed gastric ulcers who had received roxatidine acetate was conducted to determine the ulcer recurrence rates during 6 months' maintenance therapy with roxatidine acetate 75 mg at night. Gastric ulcer relapses occurred in 35% of patients, representing a worst possible outcome estimate, with no significant differences between smokers and non-smokers although heavy smoking appeared to increase the rate of relapse. The incidence of epigastric pain did not significantly increase over the duration of therapy and while some patients complained of mild pain at the start of the trial all subjects had endoscopically confirmed healed ulcers. The consumption of antacids for symptom relief was low, reaching an average of 0.75 tablets a day which was insufficient to influence intragastric pH. Continuous poor appetite and pyrosis were reported by about 5% of subjects. Of 2 patients who complained of mild to moderate side effects, 1 discontinued treatment. In addition, there were no clinically significant changes in haematological and biochemical variables. Thus, maintenance therapy with roxatidine acetate 75 mg at night is safe and generally effective in preventing symptomatic relapse. PMID- 2905244 TI - Antisecretory drugs. Safe and effective? AB - Surveillance of takers of the antisecretory drug cimetidine has failed to reveal any disturbing trends. This pattern is reassuring but the difficulties of detecting drug-induced disease mimicking ordinary community complaints deserve emphasis. Experience since the surveillance study began has not revealed any disturbing trends. Observed mortality rates have fallen to match population expectation, both for ordinary disease and for cancer. The pattern is generally reassuring and suggests that significant drug-induced disease is not being missed. Nevertheless the ability of this or any other surveillance study to detect drug-induced illness mimicking ordinary disease is likely to be low. PMID- 2905245 TI - The use of roxatidine acetate in fasting patients prior to induction of anaesthesia as prophylaxis against the acid aspiration syndrome. AB - Aspiration pneumonitis is one of the major causes of anaesthesia related deaths. H2-receptor antagonists are effective drugs for the prevention of the acid aspiration syndrome (Mendelson's syndrome). The new long-acting H2-receptor antagonist roxatidine acetate may be the first H2-receptor antagonist which could effectively reduce acid secretion following a single bedtime premedication on the evening before an operation. A prospective controlled randomised double-blind study was conducted in 60 elective patients undergoing gynaecological operations requiring tracheal intubation. 30 patients received oral roxatidine acetate 150 mg at 10 pm, the other 30 patients received placebo. Immediately after intubation, at 15 minutes and at the end of the operation gastric pH and the volume of the aspirate were measured. In the placebo group, 13 patients (43%) had gastric pH values below the critical value of 2.5, while in the roxatidine acetate group gastric pH values were raised above 2.5 in all but 3 patients (10%) [p less than 0.05]. In the roxatidine acetate group pH values were significantly higher than in the placebo group (p less than 0.01). The mean gastric volume in the placebo group was 23.3 +/- 27.1 ml, compared to 14.5 +/- 9.4 ml for roxatidine acetate. The 5 highest gastric volumes were observed in the placebo group (max 146 ml). A single bedtime oral premedication with roxatidine acetate 150 mg ensures a gastric pH above 2.5 until 11 am the following day. PMID- 2905246 TI - Comparative pharmacology of histamine H2-receptor antagonists. AB - There was no significant difference between the concentration-dependent inhibitory effects produced by roxatidine acetate, roxatidine and ranitidine on adenylate cyclase derived from isolated and enriched guinea-pig parietal cells. All the compounds shifted the concentration-response curve of histamine to the right and transformation of this data to Schild-plots produced straight lines with slopes greater than 1 but not significantly different from each other. The pA2 values characterising the potencies were roxatidine acetate 6.85 +/- 0.86, roxatidine 7.14 +/- 0.04, and ranitidine 6.92 +/- 0.01. Histamine-stimulated acid production from isolated guinea-pig parietal cells, measured by the 14C aminopyrine accumulation technique, was similarly affected by the 3 compounds. Schild-plot slopes of roxatidine acetate and ranitidine were not significantly different from unity and pA2 values were similar to those of the adenylate cyclase inhibition, roxatidine acetate 7.15 +/- 0.09, roxatidine 7.03 +/- 0.02, and ranitidine 6.83 +/- 0.10. In conclusion, roxatidine acetate and its major metabolite roxatidine behave like competitive antagonists with potencies similar to ranitidine on H2-receptors on the guinea-pig parietal cell. PMID- 2905247 TI - A review of the animal pharmacology of roxatidine acetate. AB - Roxatidine acetate (TZU 0460/HOE 760) [N-(3-[3-(1-piperidinylmethyl)-phenoxy] propyl)acetoxyacetamide hydrochloride] is a specific and competitive H2-receptor antagonist with a chemical structure different from those of cimetidine, ranitidine and famotidine. Roxatidine acetate and its main metabolite roxatidine inhibit histamine-induced gastric acid secretion in vitro with a potency greater than that of cimetidine, and in the range of that produced by ranitidine. Gastric acid secretion following stimulation with dibutyryl cyclic adenosine monophosphate remains unaffected by roxatidine acetate. In vivo experiments in rats and dogs confirm these in vitro findings. Thus, in rats roxatidine acetate inhibits gastric acid secretion with similar values following intraduodenal or intraperitoneal injection, indicating excellent absorption of the drug from the gastrointestinal tract. In all studies it was shown that roxatidine acetate was more potent than cimetidine. In rats single or repeated dosing with roxatidine acetate did not influence drug metabolising enzymes in the liver nor did the drug show antiandrogenic activity in long term animal studies. Extensive general pharmacological studies with roxatidine acetate demonstrate the lack of effects on the central nervous system, on gastrointestinal motility, the autonomic nervous system and the cardiovascular and urogenital systems. Studies on the pharmacokinetics and metabolism of roxatidine acetate demonstrate that there is a presystemic deacetylation producing the main metabolite roxatidine, which is responsible for the in vivo effects of the drug. PMID- 2905248 TI - Pharmacokinetics of roxatidine in healthy volunteers. AB - This paper reviews those studies which investigated the absorption, distribution, metabolism and elimination of roxatidine acetate (formerly HOE 760) following its single and multiple oral administration to healthy male and female volunteers. Roxatidine acetate is almost completely (greater than 95%) absorbed after oral administration and is rapidly converted to roxatidine, its major active plasma and urinary metabolite. In common with many other prodrugs, the parent substance is not detectable in either plasma or urine and therefore all pharmacokinetic studies have been evaluated using measurements of roxatidine. A powder capsule formulation of the drug showed rapid absorption (tmax = 1 hour) and linear pharmacokinetics across the dose range 25 to 100mg, but produced some gastrointestinal intolerance. However, a granulated capsule formulation showed a much slower release (tmax = 3 hours) and was well tolerated. There was no evidence of any food interaction or interaction with other drugs such as antipyrine and propranolol. The plasma terminal half-life of the granulated capsule averaged 6 hours and between 55 and 60% of the dose was recovered in the urine as roxatidine. Following repeated daily administration of the prodrug, steady state plasma levels of roxatidine were reached on average by the fourth dose. PMID- 2905249 TI - A pharmacokinetic study of roxatidine acetate in chronic renal failure. AB - The pharmacokinetics of a single oral dose of roxatidine acetate 150 mg were studied in 31 patients with varying degrees of chronic renal failure. The patients were divided into 5 groups according to their creatinine clearance (Clcr): controls (Clcr 94.5 +/- 13.9 ml/min; n = 6); mild chronic renal failure (Clcr 47 +/- 6 ml/min; n = 4); moderate chronic renal failure (Clcr 27.3 +/- 3.1 ml/min; n = 4); severe chronic renal failure (Clcr 12.8 +/- 1.4 ml/min; n = 5) and uraemia (Clcr 6.6 +/- 0.6 ml/min; n = 12). Serum and urine samples were analysed with capillary gas chromatography to measure the salt of the desacetyl metabolite of roxatidine acetate (roxatidine). The terminal half-life was 6.02 +/ 0.31 hours in controls and 7.35 +/- 0.57, 9.3 +/- 0.83, 14.6 +/- 3.7 and 18.10 +/- 2.77 hours, respectively, in the 4 other groups, with progressively decreasing creatinine clearance. Maximum serum concentration and time to maximum serum concentration rose from 816 +/- 75 ng/ml and 2.08 +/- 0.22 hours, respectively, in controls to 1364.7 +/- 156 ng/ml and 4.05 +/- 0.47 hours, respectively, in uraemic patients. Relative total clearance progressively decreased with decreasing glomerular filtration rate (GFR) [from 353.6 +/- 26 ml/min in controls to 90.31 +/- 12.2 ml/min in patients with uraemia]. Renal clearance decreased from a control of 243.9 +/- 56 ml/min to 12.32 +/- 0.18 ml/min in uraemic patients. A linear correlation between creatinine clearance and both relative total clearance and renal drug clearance was noted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2905250 TI - The pharmacodynamics and pharmacokinetics of multiple doses of the new H2 receptor antagonist, roxatidine acetate, in healthy men. AB - Roxatidine acetate (HOE 760, TZU 0460) is a new H2-receptor antagonist which is more potent than cimetidine and ranitidine. A randomised, double-blind, placebo controlled study was conducted in healthy men to determine the effects of multiple oral doses of roxatidine acetate on unstimulated gastric acid secretion, and to assess the preliminary multiple-dose pharmacokinetics of its active desacetyl metabolite. The subjects were randomised to receive either roxatidine acetate 150 mg or placebo daily at 9 pm for 14 days. Gastric secretions were collected by aspiration using a nasogastric tube placed in the distal part of the stomach. Gastric fluid volume, pH, and acid concentrations were determined for 2 hours before drug administration and over 24 hours after administration on days 1, 7, 14 (the last day of dosing), and 17 (3 days after the last dose). Plasma and urine samples were collected throughout the study for the pharmacokinetic assessment. All subjects completed the study without side effects or clinically significant changes in any of the safety variables. Subjects receiving roxatidine acetate had substantial increases in gastric pH and decreases in acid secretion compared to baseline and to placebo-treated subjects. The duration of effect was approximately 12 hours. Nocturnal pH was greater than or equal to 6.0 in 80% of the roxatidine acetate-treated subjects. When sampled 3 days after the last dose (day 17) no differences in pH, acid secretion, or gastric volume were observed between the roxatidine acetate- and placebo-treated groups. The gastric pH increased with the mean plasma concentrations of the desacetyl metabolite. Mean plasma levels at steady state were attained between the 4th and 7th days after which there was no evidence of appreciable accumulation of the desacetyl metabolite. Roxatidine acetate 150 mg administered orally at 9 pm for 14 days to healthy men was safe, well tolerated, and produced clinically relevant increases in gastric pH, and decreases in gastric acid concentration, without affecting gastric fluid volume. PMID- 2905251 TI - Effect of roxatidine acetate on daytime and night-time peptone-stimulated gastric acid secretion. AB - A double-blind, randomised, crossover study in 12 healthy volunteers was performed to assess the effects of roxatidine acetate 75 mg or placebo administered at 8 am and 9 pm on peptone-stimulated hydrochloric acid secretion. In comparison to placebo, roxatidine acetate produced an average reduction of daytime hydrochloric acid output of 86% and 32%, respectively, for the 4- to 6 hour and 10- to 12-hour post-drug administration phases. In addition, roxatidine acetate produced reductions in nocturnal hydrochloric acid output of 75 to 92% with an associated rise in intragastric pH of around 2 units compared to placebo. No side effects or clinically significant alterations in haematological or biochemical values were reported following roxatidine acetate administration. These results suggest that roxatidine acetate is a potent and effective inhibitor of day and night-time intragastric acid secretion. PMID- 2905252 TI - The effects of roxatidine acetate on 24-hour intragastric acidity. Investigations in healthy volunteers and comparison with ranitidine and placebo. AB - In a series of double-blind randomised studies in normal volunteers with continuous intragastric pH monitoring, the effects of different dosage regimens of roxatidine acetate, a new H2-receptor antagonist, were compared with placebo and ranitidine. Roxatidine acetate 75 mg twice daily decreased median 24-hour gastric acidity from pH 1.6 to 3.2 and median nocturnal acidity from 1.5 to 3.0. Roxatidine acetate 150 mg at bedtime raised median 24-hour pH in the same 17 subjects to 2.4 and nocturnal pH to 5.9. In the second experiment, in 14 volunteers, roxatidine acetate 150 mg at bedtime was as effective as ranitidine 300 mg at night, raising median nocturnal pH from 1.4 to 6.65 compared to 6.7 for ranitidine. However, when drugs were taken after the evening meal (post cenam nocte; PCN) roxatidine acetate 150 mg was less potent than ranitidine 300 mg, with median night-time pH rising from 1.3 to 3.2 and 4.0, respectively, in 28 volunteers. Roxatidine acetate 300 mg PCN produced the greatest rise of pH, to 4.9, suggesting that the true potency ratio of the 2 drugs is between 1 and 2. PMID- 2905253 TI - Effects of roxatidine acetate on 24-hour gastric acidity. Early evening versus bedtime administration in healthy subjects. AB - The gastric antisecretory activity of roxatidine acetate was studied on 24-hour intragastric pH in 12 healthy male volunteers. The study was randomised, double blind and double-dummy where either roxatidine acetate 150 mg as a slow release granulated formulation or placebo were administered at 7.30 pm or 10 pm. Roxatidine acetate 150 mg produced a significant decrease in the number of hours during which gastric acidity ranged between pH 1.5 and 4.0 which was consistent with the pharmacokinetic profile of the drug. There was no significant difference between the median intragastric pH values for early evening and bedtime administration of roxatidine acetate. The present data confirm that roxatidine acetate 150 mg inhibits gastric acid secretion but while a single evening dose is effective in controlling intragastric pH the results suggest there is no clear advantage in an early evening dose compared with a bedtime dose. PMID- 2905254 TI - Interaction of roxatidine acetate with antacids, food and other drugs. AB - The inhibition of hepatic mixed-function oxidase microsomal enzymes by cimetidine can lead to clinically important drug interactions. The metabolism of antipyrine is used as an index of hepatic enzymatic activity. The pharmacokinetic profiles of salivary antipyrine obtained following treatment with roxatidine acetate 75 mg or placebo twice a day for 7 days showed similar characteristics with no difference in the areas under the plasma concentration-time curves. In addition, roxatidine acetate 75 mg daily did not modify the clearance of propranolol, diazepam, desmethyldiazepam or controlled release theophylline preparations. Furthermore, there was no interference in the bioavailability of roxatidine acetate 150 mg daily when administered alone or in combination with a meal or antacids. PMID- 2905255 TI - A comparison of roxatidine acetate and ranitidine in duodenal ulcer healing. AB - A randomised double-blind study was conducted to compare the efficacy of roxatidine acetate 75 mg twice daily with ranitidine 150 mg twice daily in 308 patients with endoscopically confirmed uncomplicated duodenal ulcers. After 6 weeks of treatment ulcer healing was found in 93.5% of the roxatidine acetate group and 89.2% of the ranitidine group, with no significant differences between treatment groups. The relief of day and night-time epigastric pain assessed at clinic visits or on diary cards by patients was comparable for both treatment groups, as was the consumption of antacid tablets for relief of symptoms of dyspepsia. There were no significant differences in the healing rates of smokers and non-smokers for either roxatidine acetate or ranitidine treatment, and no clinically significant alterations in laboratory values. Eight patients in the roxatidine acetate group and 1 in the ranitidine group complained of mild side effects, which included diarrhoea, constipation and headache. One patient on roxatidine acetate withdrew from treatment because of a mild skin rash. The results confirm that roxatidine acetate is a safe and effective treatment for duodenal ulcer disease. PMID- 2905256 TI - A comparison of roxatidine acetate 150 mg once daily and 75 mg twice daily in duodenal ulcer healing. AB - A randomised multicentre, double-blind study of the efficacy and safety of roxatidine acetate 150 mg at bedtime or 75 mg twice a day was conducted in 300 outpatients with endoscopically confirmed duodenal ulcers. After 14 days' treatment with roxatidine acetate substantial reductions in ulcer sizes had been obtained, in addition to healing rates of 87 to 89%, with no significant differences between the dosage regimens. There were graded reductions in day and night-time assessment of epigastric pain for both treatment groups and no differences in the mean numbers of antacid tablets consumed. In addition, cigarette smoking did not influence the healing rates produced by either treatment schedule. 11 patients reported 12 mild adverse reactions, with gastrointestinal symptoms the most frequent, and no clinically significant alterations in laboratory values. The present data suggests that a single bedtime dose of roxatidine acetate 150 mg produces effective duodenal ulcer healing and pain relief equivalent to that produced by a twice daily dosage regimen. PMID- 2905257 TI - [Changes in sensitivity of lymphocyte cholinergic receptors in patients with breast cancer]. AB - Alteration of the cholinoreceptor sensitivity of peripheral blood lymphocytes in patients with breast cancer was studied by the lymphocyte adhesion inhibition test (LAI-test). It has been shown that acetylcholine stimulates the LAI-reaction in optimal concentrations of 10(-7)-10(-8) M. Specific antagonists (m cholinoblocker of atropin and n-cholinoblocker of hexonium) being used, it is demonstrated that the revealed cholinergic enhancement of the lymphocyte adherence inhibition is mediated through the stimulating influence of acetylcholine on m-cholinoreceptors. It is established that the lymphocyte cholinoreceptor sensitivity of the patients with breast cancer at the advanced stages is significantly lower than in patients with breast cancer at early stages. PMID- 2905258 TI - Characterization and comparison of the role of beta-agonists on in vivo and in vitro surfactant-related phospholipid synthesis and secretion by fetal rabbit lung and isolated type II alveolar cells. AB - The role of beta-adrenergic stimulation in surfactant synthesis and secretion was investigated in the fetal lung. Fetuses were treated with isoxsuprine or saline on gestational day 24 by ip injection. Three days later the fetal lungs were lavaged and intracellular surfactant was isolated on a sucrose gradient. Concurrently undifferentiated type II alveolar cells were isolated from 24-day fetal rabbit lung and grown in vitro. In the in vivo portion of the study, examination of surfactant pool sizes revealed that only saline treatment produced a significant elevation in tissue-stored or secreted surfactant compared to untreated controls. Isoxsuprine appeared to inhibit the saline-induced increase. In the case of the intracellular surfactant, the phosphatidylcholine content per gram of lung was significantly increased after saline treatment. In vitro response of isolated type II alveolar cells to isoxsuprine was dependent on prior incubation of the cells for 24 h with conditioned medium. Isoxsuprine stimulated a dose-dependent decrease in the intracellular stores of radioactively labeled DSPC after 24 h of exposure to the drug. A corresponding increase in labeled DSPC in the culture medium was observed. Forth-eight hours after exposure to the drug, those cells that had secreted the highest level of DSPC displayed the highest levels of renewed synthesis of DSPC. This study indicates that the immature fetal lung can be induced to synthesize surfactant-related phospholipid by the stress of laparotomy and/or drug administration. Short-term exposure to beta-agonists is insufficient to stimulate secretion of surfactant stores. In contrast, isolated type II alveolar cells exposed to isoxsuprine respond by secreting DSPC. PMID- 2905259 TI - Protein deficiency potentiates oxygen toxicity. AB - Male rats (Charles River COBS-CD derived) fed protein-deficient diets showed enhanced toxicity with failure of elevation of lung glutathione levels with exposure to greater than 98% O2. Replenishment of S-containing amino acids in the protein-deficient diets allowed elevation of lung glutathione and prevention of enhanced toxicity. Studies with endothelial cell cultures exposed to hyperoxia showed elevation of cellular glutathione coupled with enhanced uptake of amino acid precursors of glutathione. We postulate that hyperoxia causes an enhancement of uptake of S-containing amino acids necessary for glutathione synthesis, overriding glutathione feedback of its own synthesis. Limitation of available S containing amino acids prevents elevation of glutathione synthesis and is detrimental to the cell exposed to hyperoxia. PMID- 2905260 TI - A new locus (NIA 1) in Arabidopsis thaliana encoding nitrate reductase. AB - We have isolated two nitrate reductase genes and their corresponding cDNAs from Arabidopsis thaliana. Sequences of the two cDNAs, when compared to a sequence of a barley cDNA clone, confirm their identity as nitrate reductase clones and show that they are closely related. The two genes have been mapped using restriction fragment length polymorphisms; gNR2 is close to the previously identified chl-3 locus and is probably identical to it, while gNR1 maps to a new locus (NIA1) on chromosome 1, near gl-2. PMID- 2905261 TI - Receptors compete for adaptors found in plasma membrane coated pits. AB - An affinity matrix of LDL receptor cytoplasmic tails binds the HA-II 100/50/16 kd complexes found in plasma membrane coated pits. Other receptors (or their cytoplasmic domains), which are localized in coated pits during endocytosis, inhibit this binding. This includes an 8 residue peptide containing tyrosine, corresponding to the cytoplasmic portion of a mutant influenza haemagglutinin. In contrast, the equivalent peptide lacking tyrosine (like the tail of the native haemagglutinin, a protein excluded from coated pits) does not compete. These results imply that the HA-II complex has a recognition site for a common signal, probably involving a tyrosine residue, carried by the LDL receptor and competing receptors also found in plasma membrane coated pits. The HA-II complex therefore fulfils the role of an 'adaptor', the name proposed for the structural units which mediate the binding of clathrin to receptors in coated vesicles. Another related complex, the HA-I adaptor, which is restricted to Golgi coated pits, probably does not recognize the 'tyrosine signal' on the LDL receptor tail. The HA-I adaptor is likely to contain a recognition site for a different signal carried by receptors, e.g. the mannose-6-phosphate receptor, which are found in Golgi coated pits. PMID- 2905262 TI - Combinatorial expression of a ftz-zen fusion promoter suggests the occurrence of cis interactions between genes of the ANT-C. AB - The nine homeobox genes contained within the Antennapedia gene complex (ANT-C) are precisely regulated during embryonic development. It is not known to what extent the physical linkage of these genes contributes to their normal patterns of expression. Here we show that cis regulatory elements associated with one homeobox gene can act over a long distance (approximately 20 kb) to influence the expression of another homeobox gene. Specifically, fushi tarazu (ftz) promoter elements can direct the periodic expression of the z2 gene, which normally shows a simple 'dorsal on/ventral off' pattern of expression. An 80 kb deletion within the ANT-C [Df(3R)LIN] juxtaposes the z2 and ftz promoters, resulting in a hybrid expression pattern whereby z2 transcripts are distributed within periodic stripes that are confined to dorsal and lateral tissues and not observed in the ventral mesoderm. This observation suggests that separate promoter elements of different genes can function in a combinatorial manner, and that the patterns of ANT-C gene expression might depend on cis regulatory interactions. PMID- 2905263 TI - Increased turnover of the messenger RNA encoding tyrosine aminotransferase can account for the desensitization and de-induction of tyrosine aminotransferase by 8-bromo-cyclic AMP treatment and removal. AB - Treatment of H-4 rat hepatoma cells with 8-bromo-cyclic AMP (8-Br-cAMP) resulted in a transient induction of the gluconeogenic enzyme tyrosine aminotransferase. Synthesis of tyrosine aminotransferase and the level of its corresponding mRNA peaked 2 h after the addition of the cyclic nucleotide and declined thereafter. Tyrosine aminotransferase synthesis and mRNA failed to respond to the readdition of fresh 8-Br-cAMP, a process which we defined as desensitization. Removal of 8 Br-cAMP resulted in a decrease in tyrosine aminotransferase synthesis and mRNA, a process defined as de-induction. The relative transcription rate of the tyrosine aminotransferase gene and the turnover of its mRNA were determined by labeling intact cells with [3H]uridine. 8-Br-cAMP led to an increase in the rate of tyrosine aminotransferase transcription which was sustained for at least 4 h. The transcription rate declined upon de-induction. In addition, 8-Br-cAMP increased the turnover rate of tyrosine aminotransferase mRNA, but only after a 1.5-3 h time lag. This increased degradation rate persisted for at least 1.5 h after the removal of 8-Br-cAMP. These two contrasting and temporally distinct processes could account for the observed changes in tyrosine aminotransferase mRNA levels in response to 8-Br-cAMP treatment and removal. PMID- 2905264 TI - Import of proteins into yeast mitochondria: the purified matrix processing protease contains two subunits which are encoded by the nuclear MAS1 and MAS2 genes. AB - We have purified the metalloprotease which is localized in the soluble matrix space of Saccharomyces cerevisiae mitochondria and cleaves the amino-terminal matrix-targeting sequences from imported mitochondrial precursor proteins. The enzyme consists of two loosely associated non-identical subunits of mol. wt 48,000 and 51,000, respectively. Attempts to separate the two subunits from each other caused loss of activity. The smaller subunit had been identified as the product of the nuclear MAS1 gene (Witte et al., 1988). The larger subunit is now identified as the product of the nuclear MAS2 gene. PMID- 2905265 TI - Secretion of cyclolysin, the calmodulin-sensitive adenylate cyclase-haemolysin bifunctional protein of Bordetella pertussis. AB - The calmodulin-sensitive adenylate cyclase of Bordetella pertussis, a 45 kd secreted protein, is synthesized as a 1706 amino acid precursor. We have shown that this precursor is a bifunctional protein, carrying both adenylate cyclase and haemolytic activities. The 1250 carboxy-terminal amino acids of the precursor showed 25% similarity with Escherichia coli alpha-haemolysin (HlyA) and 22% similarity with Pasteurella haemolytica leucotoxin. Three open reading frames were identified downstream from the cyaA gene: cyaB, cyaD and cyaE, coding for polypeptides of 712, 440 and 474 amino acid residues, respectively. As for E. coli alpha-haemolysin, secretion of B.pertussis adenylate cyclase and haemolysin requires the expression of additional genes. The gene products of cyaB and cyaD are highly similar to HlyB and HlyD, known to be necessary for the transport of HlyA across the cell envelope and for its release into the external medium. Complementation and functional studies indicate that the B.pertussis adenylate cyclase-haemolysin bifunctional protein is secreted by a mechanism similar to that described for E.coli alpha-haemolysin, requiring, in addition to the cyaB and cyaD gene products, the presence of a third gene product specified by the cyaE gene. PMID- 2905266 TI - One-year follow-up of panic disorder. Outcome and prognostic factors. AB - A 1-year follow-up study was carried out in 77 patients with panic attacks (panic disorder). Of these patients 43% were remitted; avoidance behaviour and chronic anxiety were more persistent than panic attacks within the 1-year period. The main predictor for features of anxiety in the follow-up was avoidance behaviour. The most prominent prognostic factor for features of depression was the history of previous depressive episodes. Female patients had a poorer outcome than male patients. PMID- 2905267 TI - Differential effects of EEDQ on the dopamine D-1 receptor in vivo and in vitro. AB - As measured in vitro by means of [3H]SCH 23390 saturation analysis, 5 and 10 mg/kg (i.p., 24 h) of EEDQ caused a 70% reduction and 20 mg/kg and 80% reduction in the numbers of D-1 receptors. In vivo, also measured by [3H]SCH 23390 saturation analysis, 5 mg/kg of EEDQ caused no significant reduction in the D-1 receptor number whereas 10 and 20 mg/kg caused a 40 and 70% reduction, respectively. This difference in sensitivity to EEDQ in vivo as compared to in vitro suggests that EEDQ only destabilizes the D-1 receptor, whereas the inactivation occurs during preparation of the tissue for in vitro binding. Thus, caution should be exercised when animals depleted of D-1 receptors by EEDQ are used for behavioral studies. PMID- 2905268 TI - Disparate effects of neuropeptide Y and clonidine on the excretion of sodium and water in the rat. AB - Previous studies have demonstrated a similarity between the ability of neuropeptide Y (NPY) and clonidine to inhibit renin release and inhibit cAMP production. We therefore compared the effects of clonidine and NPY on the excretion of sodium and water in anesthetized rats which were unilaterally nephrectomized (right kidney) 10 days prior to the experiment. On the experimental day, rats were anesthetized (nembutal) and the left kidney exposed for the intrarenal infusion of the study drugs. The lowest dose of NPY (0.3 microgram/kg per min) investigated failed to alter renal function. Clonidine (0.3 microgram/kg per min) and NPY (1 microgram/kg per min) produced a similar increase in urine volume. Only NPY increased sodium excretion and osmolar clearance. Free water clearance was only increased by clonidine. Blood pressure and creatinine clearance were similar in all groups investigated. These effects were attenuated by pretreatment with pertussis toxin (5 days). The ability of pertussis toxin to block these effects suggests that the renal effects of NPY and clonidine are coupled to a G protein, conceivably the inhibitory Gi protein of the adenylate cyclase system. The disparate effects on sodium excretion and on free water and osmolar clearance indicate that the effects of these compounds may be mediated through the inhibition of different pools of hormonally stimulated cAMP. PMID- 2905269 TI - Peripheral and central antinociceptive actions of ethylketocyclazocine in the formalin test. AB - The antinociceptive actions of ethylketocyclazocine and morphine were examined in rats in a thermal nociceptive test (tail-immersion) and a test involving minor tissue injury (formalin). In the formalin test, the antinociceptive effects of high doses of ethylketocyclazocine, but not morphine, were attenuated by the peripherally acting antagonist naloxone methylbromide. Naloxone methylbromide had no effect on antinociception produced by ethylketocyclazocine in the tail immersion test. When ethylketocyclazocine was injected intraventricularly, only partial antinociception was observed in the formalin test. Conversely, naloxone given intraventricularly only partially attenuated the antinociception produced by ethylketocyclazocine given systemically. The data indicate that the antinociceptive effects of ethylketocyclazocine in the tissue injury-induced nociception are a result of summation of central and peripheral actions. Morphine antinociception reaches ceiling at doses that are devoid of such peripheral actions. The data imply that it may be possible to develop a new class of peripherally acting analgesics that are effective in acute inflammatory pain. PMID- 2905270 TI - Increased grooming behaviour is induced by apomorphine in mice treated with discriminant benzamide derivatives. AB - Grooming behaviour in mice was dose dependently increased by SK&F 38393 (1.87-30 mg/kg), whereas it was dose dependently decreased by RU 24926 (2.5-10 mg/kg) or LY 171555 (0.4-1.6 mg/kg) alone or combined with SK&F 38393 or apomorphine (0.39 6 mg/kg). The inhibitory effect of 0.75 mg/kg apomorphine on grooming behaviour was not modified by SCH 23390, chlorpromazine, clozapine and thioridazine. In contrast, it was antagonized by eight other dopamine antagonists: a partial restoration to grooming scores lower or similar to those determined in control mice was obtained with flupentixol, haloperidol, metoclopramide, thioproperazine and tiapride, whereas a reversal to grooming scores higher than those determined in control mice was obtained with mice treated with (+/-)-sulpiride, amisulpride or RIV 2093. Furthermore, only SCH 23390, chlorpromazine and clozapine antagonized SK&F 38393 (1.87 mg/kg)-induced grooming behaviour, whereas the effects of flupentixol, thioridazine, metoclopramide, haloperidol and amisulpride in SK&F 38393-treated mice were parallel to those of control mice. Finally, SCH 23390 (20 micrograms/kg) antagonized the apomorphine-induced grooming in mice treated with amisulpride, (+/-)-sulpiride or tiapride. These data confirm the potential role of D-1 dopamine receptors in the expression of grooming behaviour and indicate that the dopamine receptors involved in the inhibition of grooming could be of the D-4 subtype. Our results also reveal that chlorpromazine and clozapine have D-1 antagonist properties and suggest that the modulation of apomorphine-induced grooming behaviour by dopamine antagonists in mice could be used as a test for their classification according to their activity at the different dopamine receptor subtypes. PMID- 2905271 TI - 6,7-Dinitro-quinoxaline-2,3-dion and 6-nitro,7-cyano-quinoxaline-2,3-dion antagonise responses to NMDA in the rat spinal cord via an action at the strychnine-insensitive glycine receptor. AB - 6,7-Dinitro-quinoxaline-2,3-dion (DNQX) and 6-nitro,7-cyano-quinoxaline-2,3-dion (CNQX) produce an unsurmountable antagonism of responses to N-methyl-D-aspartate (NMDA) in the baby rat hemisected spinal cord. These effects of DNQX and CNQX can be prevented in a dose-dependent manner by co-superfusion with D-serine or glycine (in the presence of strychnine). The results suggest that the unsurmountable blockade of NMDA responses by DNQX and CNQX reflects an antagonist effect mediated at the allosterically linked strychnine-insensitive glycine receptor. PMID- 2905272 TI - Improving palatal attachments. PMID- 2905273 TI - Intra-ventricular infusion of the NMDA antagonist AP5 impairs performance on a non-spatial operant DRL task in the rat. AB - Rats were trained to lever press on a differential reinforcement of low rates (DRL-18 s) schedule. They were then allocated to four treatment groups. These were: hippocampal aspiration lesions [HIPP]; implantation of osmotic minipumps for intraventricular infusion of either (a) the NMDA receptor antagonist 30 mM D, L-2-amino-5-phosphonopentanoic acid [AP5] or (b) vehicle [VEH]; and an unoperated control group [UNOP]. In subsequent DRL testing, the HIPP group showed a profound and enduring loss of efficiency, resulting from an increased tendency to respond too early; the AP5 group showed a qualitatively similar, but less severe, impairment followed by full recovery once the minipumps had expired; the VEH and UNOP groups both maintained their pre-operative levels of efficiency. We conclude that AP5 infusion disrupts temporary memory storage in the hippocampus, and that the hippocampus is concerned with the retention of memories outside the purely spatial domain. PMID- 2905274 TI - HIV-serology and lymphocyte subsets in relation to therapy and clinical development in haemophiliacs. AB - 389 Swedish patients with haemophilia A, B or von Willebrand's disease were examined for HIV-1 antibodies. T-cell subsets were measured in 260 of them. HIV-1 antibodies were found in 98 of these patients. Of the 199 patients with severe or moderate haemophilia A, 44% were seropositive. They had seroconverted between 1979 and 1983. HIV-1-seropositive patients had significantly decreased numbers of CD4 cells and increased numbers of CD8 cells. The seronegative haemophilia A patients had significantly increased numbers of CD8 cells. The T-cell subsets were followed for a median of 40 months in 73 seropositive patients. All groups of patients, at different clinical stages, showed decreasing numbers of CD4 cells. The most pronounced decrease was seen in the patients who developed AIDS, followed by the group which developed HIV-related signs or symptoms. HIV antigen in serum and antibody pattern in Western blot and ELISA were followed in 89 patients. HIV-1 antigen was present and p24 antibodies were lacking in 11% and 13% of asymptomatic subjects, in 13% and 20% of patients with persistent generalized lymphadenopathy, in 33% and 38% of patients with other HIV-related signs or symptoms and in 5/6 of the AIDS patients, respectively. In conclusion, the decrease of CD4 cells and the presence of HIV antigen and/or absence of p24 antibodies were found to be prognostic markers for HIV disease. PMID- 2905275 TI - [Neurotropic effects of tranquilizers administered intrathecally]. AB - The effects of intrathecally administered benzodiazepines diazepam, flurazepam and flunitrazepam on the pain thresholds in rats were studied by using chronically implanted catheters. Despite benzodiazepine-induced marked muscle relaxation and sedative effect, benzodiazepines produced no significant changes in the thresholds during tests of tail flick and paw compression whereas morphine was effective in both tests. Experiments with 14C-diazepam and 3H-flunitrazepam showed that after intrathecal administration these substances rapidly enter the brain. It was found that 10-15 minutes after intrathecal administration 3H flunitrazepam concentration in the frontal parts of the brain is 1/4 of its concentration in the lumbar spinal cord. The data suggest that these benzodiazepines possess no antinociceptive activity at intrathecal administration to rats and that way of administration fails to prevent their action on the brain. PMID- 2905276 TI - [Mechanisms of the thrombocytic effects of beta-adrenoblockaders]. AB - Beta-adrenoblockers were found to be able of suppressing platelet aggregation through beta 2-subtype of adrenoreceptors. This is due to the membrane stabilizing action of beta-adrenoblockers which by binding to the receptors decrease microviscosity of the membranes and prevent the opposite shift under the influence of aggregation inductors. PMID- 2905277 TI - [The protective effect of pantothenic acid derivatives and changes in the system of acetyl CoA metabolism in acute ethanol poisoning]. AB - Calcium pantothenate (CaP), calcium 4'-phosphopantothenate (CaPP), pantethine, panthenol, sulfopantetheine and CoA decrease acute toxicity of acetaldehyde in mice. All studied compounds diminish duration of the narcotic action of ethanol- ET (3.5 g/kg intraperitoneally) in mice and rats. In the latter this effect is realized at the expense of "long sleeping" and "middle sleeping" animals. CaP (150 mg/kg subcutaneously) and CaPP (100 mg/kg subcutaneously) prevent hypothermia and a decrease of oxygen consumption in rats induced by ET administration. Combined administration of ET, CaP and CaPP leads to a characteristic increase of acid-soluble CoA fractions in the rat liver and a relative decrease of acetyl CoA synthetase and N-acetyltransferase reactions. The antitoxic effect of preparations of pantothenic acid is not mediated by CoA dependent reactions of detoxication, but most probably is due to intensification of ET oxidation and perhaps to its elimination from the organism. PMID- 2905278 TI - [The organization of ambulatory care at feldsher-midwife centers]. PMID- 2905279 TI - [Professional violations of the law by paramedical personnel and their prevention (2)]. PMID- 2905280 TI - Ultrastructure of the APUD-like cells of the frog thymus gland. AB - Within the thymus gland of the European common frog, Rana temporaria, cells with endocrine- like appearance have been found. At the ultrastructural level the most characteristic feature of their cytoplasm is the presence of secretory granules. Some cells possess irregular electron lucent granules with an eccentrically located dense core while others possess smaller electron dense granules. The cytoplasm contains also cisterns of rough endoplasmic reticulum, free ribosomes, and small mitochondria. The cells possess irregular nuclei with the pronounced nucleoli. These endocrine-like cells are connected by desmosomes with neighbouring non-granulated epithelial cells. Ultrastructural features of the cells described here resemble those seen in polypeptide hormone-secreting cells belonging to the family of cells of the APUD (Amine Precursor Uptake and Decarboxylation) series. PMID- 2905281 TI - [Effect of islet activating protein on somatostatin-induced inhibition of cellular cyclic AMP content in isolated rat pancreatic acini]. AB - Our previous study concerning guanine nucleotides regulation of labeled somatostatin binding has suggested that somatostatin receptors on pancreatic acinar cell membranes probably couple with the inhibitory guanine nucleotide regulatory protein (Ni). In order to clarify the possible role of Ni in mediating signal transduction of somatostatin in the pancreas, we further examined the effect of pretreatment with islet activating protein (IAP) on the inhibition of VIP-stimulated cellular cyclic AMP content by somatostatin in isolated rat pancreatic acini. Increasing concentrations of somatostatin decreased VIP stimulated cellular content of cyclic AMP in the acini, with a maximal inhibition at 10(-8) M somatostatin. When pancreatic acini were pretreated with varying concentrations of IAP for 4 hours, the somatostatin-induced inhibition of cyclic AMP content was attenuated in a dose dependent manner by IAP pretreatment. Incubation of pancreatic acinar membrane with preactivated IAP and [32P] NAD resulted in labeling of a Mr = 41,000 protein band, consistent with alpha-subunit of Ni in many other cell types previously reported. On the other hand, a Mr = 41,000 protein band on SDS gel was reduced in a dose dependent fashion by IAP pretreatment, when acini were pretreated with increasing concentrations of IAP. These results suggest that only the Mr = 41,000 protein is a specific substrate in pancreatic acinar membranes for IAP-induced ADP-ribosylation. Furthermore, the reduction of 32P incorporation to Mr = 41,000 protein by IAP pretreatment occurred in parallel to decreases in somatostatin-induced inhibition of cellular cyclic AMP contents in pancreatic acini.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2905282 TI - Ultrasound measurement of fetal abdominal circumference and the ratio of biparietal diameter to transverse abdominal diameter in a mixed Nigerian population. AB - The fetal abdominal circumference (FAC) and biparietal diameter to transverse abdominal diameter ratio (BPD/TAD) were measured by ultrasound in 219 normal pregnant Nigerian women from 20 weeks until term using the cross-sectional method. There was a progressive linear growth of the FAC and a consistent standard deviation throughout the study period. When compared to caucasian growth curves, the curve shapes were identical but the FAC values were consistently less for each week of gestation in our Nigerian sample. The BPD/TAD ratio showed a progressive fall from 20 weeks until term similar to that previously noted for fetal head circumference to abdominal circumference ratio, indicating that this parameter may also be useful for predicting abnormal fetal growth. PMID- 2905283 TI - Postmenopausal endometrial patterns and serum estradiol concentrations. AB - Eighty postmenopausal women were subjected to endometrial biopsy. Inadequate biopsy was recorded in 30 cases. In the remaining cases (n = 50) the correlation between endometrial patterns and serum estradiol (E2) was performed. These cases were presenting with uterine bleeding (n = 38) or minor gynecological symptoms (n = 12). Proliferative endometrium was the predominant endometrial pattern whereas endometrial malignancy was only present in 15.8% of the bleeding cases. Serum E2 was significantly elevated in cases having malignant endometrium or adenomatous hyperplasia compared to cases having other endometrial patterns. Serum E2 measurement is recommended as a simple screening test for the detection of postmenopausal endometrial hyperplasia and/or malignancy. PMID- 2905284 TI - Urinary estrone glucuronide, pregnanediol glucuronide and human chorionic gonadotrophin in threatened abortion. AB - Estimations of urinary estrone glucuronide, pregnanediol glucuronide and human chorionic gonadotrophin were carried out by ELISA to see their potential in predicting an abnormal outcome in cases with vaginal bleeding in early pregnancy. Reference values were set up with samples from women without bleeding in present or past pregnancies and with normal ultrasonic findings. None of the parameters were found to be sensitive enough to predict an abnormal outcome. However, predictability of an abnormal value was found to be 95% for estrone-3-glucuronide (E1G), 93% for pregnanediol glucuronide (PdG) and 87% for human chorionic gonadotrophin (hCG). PMID- 2905285 TI - Breech births in twin pregnancy: an analysis of Apgar score and perinatal mortality from a Nigerian sample. AB - Perinatal mortality (PNM) rates are reported for 146 twin-1 and 192 twin-2 breech births among 622 consecutive twin pairs delivered at the University of Ilorin Teaching Hospital, Ilorin, Nigeria. Stillbirths and infants with severe asphyxia (Apgar score 1-3) were recorded in significant proportions of both first and second twin breech infants. PNM rates were 13.7% twin-1, 18.8% twin-2; corrected PNM for infants weighing 2.0 kg or more, were 9.3% and 12.4% for twin-1 and twin 2, respectively. Twin specific breech PNM decreased with increasing birthweight of first and second twin to a low optimum in the weight group 2.5-2.9 kg, and thereafter rose for both first and second twin with birthweight 3.0 kg and above. Factors such as low birthweight, breech/breech presentation, breech extraction and retained second twin breech contributed significantly to the high PNM rates. More favorable PNM rates were recorded among a limited number of breech infants delivered by primary cesarean section for breech/breech or first twin breech presentations. A liberal approach to cesarean section delivery for breech twin births, and particularly for paired breech/breech presentations is strongly advocated. PMID- 2905286 TI - Resurfacing the vulva and vagina. AB - Thirteen patients are described where split thickness skin grafts, cutaneous or myocutaneous flaps were used to cover large defects on the vulva and vagina. For defects over the pubic groin areas, the tensor fascia lata flaps are most suitable. Defects of the vulva are best covered by split thickness skin grafts or gracilis flaps, and vaginal defects by split thickness skin grafts or vulvar flaps. PMID- 2905287 TI - Intracervical administration of prostaglandin E2-gel prior to therapeutic abortion: a prospective randomized double-blind study. AB - Forty primigravid women due to undergo first trimester termination of pregnancy were randomly selected for intracervical application of 1 mg prostaglandin E2 in gel or gel only as placebo. In the PGE2-gel group, a marked dilatation of the cervical canal was obtained, with post-gel treatment mean Hegar dilatation of 11.18 mm in that group, compared to 4.4 mm in the control group (P 0.001). Moreover, 16 (80%) patients in the PGE2-gel group had a complete abortion, one (5%) patient had an incomplete abortion and in the remaining three (15%) patients, fetal demise was observed. The mean induction-abortion interval in this group was 7.5 h. In the placebo group, none of the above effects were observed. The only side effect noted was vomiting, which occurred in five (25%) of the patients in the PGE2-gel group. Termination of pregnancy was found to be easier in the PGE2-gel group, compared to the placebo group. PMID- 2905288 TI - Clinical experiences with the Spring Coil intrauterine device: a ten-year follow up study. AB - In a ten-year follow-up study analysing 1080 cases and 29,138 cumulative woman months of use, the clinical experiences of the Spring Coil IUD are evaluated using the life table technique, the net cumulative pertinent termination rates calculated for 100 women at the end of the 10th year, were as follows: pregnancy 1.2; expulsion 32.5; bleeding/pain removal 31.6; removal for other medical reasons 6.2. The results support the concept that in problem- and symptom-free cases, routine IUD removal is not necessary. PMID- 2905289 TI - Mitral valve prolapse and thromboembolic disease in pregnancy: a case report. AB - Mitral valve prolapse is usually a benign condition, however, serious complications have been reported to be associated with it. A report of retinal artery occlusion associated with mitral valve prolapse and pregnancy is presented. PMID- 2905290 TI - Cervico-vaginal fistula and spontaneous mid-trimester abortion. AB - An unusual complication of spontaneous second trimester abortion which was unaided by external agents is presented. We found no similar case in the literature. PMID- 2905291 TI - Inguinal ovary and fallopian tube--an unusual hernia. AB - A case of indirect inguinal hernia with an ovary and fallopian tube in the hernial sac is described. Additional evidence for developmental abnormality as a cause of this condition is advanced. PMID- 2905292 TI - AIDS and travel. PMID- 2905293 TI - Breech delivery: a critical evaluation of the mode of delivery and outcome of labor. AB - This is a retrospective study of 213 term, singleton, uncomplicated pregnancies presenting as breech. Thirty-two percent had elective cesarean section and 61% of those selected for vaginal delivery actually did so. Events in labor and fetal outcome suggest that vaginal delivery of a breech infant, after careful feto maternal assessment, continuous fetal monitoring, adequate progress in labor and delivery by an experienced "midwife", provides comparable fetal outcome to delivery by elective cesarean section. PMID- 2905294 TI - Plasma antithrombin III levels in pre-eclampsia and chronic hypertension. AB - Plasma levels of antithrombin III were tested during pregnancy in a control group of normal patients and in a study group that included patients with moderate and severe pre-eclampsia and chronic hypertension. The control group showed mean antithrombin III activity of 97.9 +/- 20.9%, the severe pre-eclamptic patients 22.33 +/- 18.22%, the moderate pre-eclamptic patients 56.0 +/- 7.56%, and the chronic hypertensive patients 77.5 +/- 6.69%. The difference between normal pregnancy and moderate pre-eclampsia was significant at P less than 0.002, normal pregnancy and severe pre-eclampsia P less than 0.002, moderate and severe pre eclampsia P less than 0.002, chronic hypertension and normal pregnancy P less than 0.1, and chronic hypertension and severe pre-eclampsia P less than 0.002. All the severe pre-eclamptic patients and 2 out of 6 of the moderate pre eclamptic women were below 55.7% (mean - 2S.D.) of normal antithrombin III activity. Patients with heavy proteinuria had depressed antithrombin III activity. However, chronic hypertensive pregnancies, although rather a small group, had almost normal values of plasma antithrombin III activity. The plasma antithrombin III value may thus help to distinguish between chronic hypertension and severe pre-eclamptic disease. PMID- 2905295 TI - Birth patterns: are the Chinese in Guangzhou City different? AB - Diurnal birth patterns in the City of Guangzhou, China and the City of Calgary in Canada were compared. Chinese data were abstracted from the labor room log book of one large general hospital located in the Hai Zhu district of Guangzhou. Calgary birth data were abstracted from birth notification forms submitted to Calgary Health Services. Information included day of birth, time of delivery, type of delivery and parity. Calgary births are concentrated on Tuesdays to Fridays whereas in Guangzhou weekly patterns varied tremendously according to whether it was assisted or unassisted. Calgary births are below average at night and during evening shift. The time of birth in Guangzhou varied substantially with above average rates for non-assisted births noted at 0800-2400 h, and above average rates for assisted births noted at 0800-1700 h. Differences in hour of birth appeared to be related to obstetric intervention practices. Knowledge of birthing patterns are useful for effective hospital management. PMID- 2905296 TI - Apgar scores and umbilical cord arterial pH in the breech neonate. AB - Apgar scores and umbilical cord arterial pH measurements of 449 singleton breech deliveries are compared retrospectively to those of 1425 singleton vertex neonates. In the vaginal deliveries the Apgar scores and umbilical arterial pH were higher for the vertex neonates. There were no differences in either Apgar scores or umbilical arterial pH between the breech and vertex neonates delivered by cesarean section. Whereas Apgar scores in the less than 1000 g and greater than or equal to 2500 g weight groups were lower in the breech neonates delivered vaginally compared to cesarean section, umbilical arterial pH measurements were similar. The data suggest that liberal use of cesarean section may improve the Apgar scores but will probably not appreciably improve the acid-base status of the breech neonate. PMID- 2905297 TI - Long term follow-up of women with hypertension in pregnancy. AB - The reproductive history and the present health status of 66 patients who had had a pregnancy complicated by hypertension during the period 1972-1982 were retrospectively studied. Hypertension in pregnancy is a poor prognostic factor not only for the future development of hypertension but, also, as it is associated to a very poor reproductive history. Such complications are more frequent in pregnant women with very high blood pressure (greater than 160/100). In fact, in the case of a previous pregnancy, this group of patients had experienced a high rate of abortions (31.7%), premature deliveries (17.8%) and perinatal mortality (21.4%). Moreover, these women are subject to a higher risk (56.5%) of developing hypertension in successive pregnancies. Risk factors for determining the future development of hypertension are: familiar hypertension, the severity of hypertension during pregnancy and pluriparity. PMID- 2905298 TI - The effect of maternal age on primary cesarean section rate. AB - A retrospective analysis of computerized data from 11,815 patients with no history of previous cesarean section revealed an increasing primary cesarean section rate with increasing maternal age. This increase occurred over the entire reproductive age span. Fetal distress as an indication for primary cesarean section may account for this increase. PMID- 2905299 TI - Nausea and vomiting in early pregnancy. AB - To study the problem of nausea and vomiting in early pregnancy an epidemiological survey was undertaken, obtaining information from 500 consecutive antenatal patients. Seventy-six percent of women complained of symptoms during the first trimester, and in only 27% had the symptoms resolved by the twelfth week. Job efficiency was markedly impaired. Women who suffered nausea premenstrually, or on the oral contraceptive pill, were much more likely to develop symptoms, lending credence to a hormonal etiology for the condition. PMID- 2905300 TI - Contribution of congenital malformation to perinatal mortality in Lagos, Nigeria. AB - Over a 17-month period we prospectively recorded identifiable congenital malformations at delivery in singleton births in our hospital. Despite the prevailing religious and cultural belief we carried out autopsies in 41% of the perinatal deaths that occurred during the study period. Out of a total of 63 (21/1000 singleton births) congenital malformations discovered, 21 (33%) were identified at autopsy only. About 16% of total perinatal deaths were due to congenital malformation. Cardiovascular malformations accounted for about 40% of perinatal deaths from congenital malformations followed by central nervous system malformation (23.3%), gastrointestinal malformations (20%), musculo-skeletal malformations (6.7%); renal malformations (3.3%) and others (6.7%). No relationship between maternal age, parity and congenital malformation was found. The results from this study suggest that with the use of autopsy, teratology may contribute significantly to the prevailing high perinatal mortality in Lagos more than was previously thought. PMID- 2905301 TI - Coupling of uterine contractions during labor: a pilot study. AB - A review of 2167 cardiotocograms revealed 53 (2.5%) with coupling of contractions. The data of these patients was compared to the data of 53 patients with cardiotocograms without coupling. In the coupling group there were more primigravidas (45 vs. 18), and a lower incidence of normal vaginal deliveries (11.3% vs. 83.0%). Vacuum and forceps deliveries occurred in 49.1% in the coupling group and cesarean births in 39.6%. The corresponding figures in the control group were 9.4% and 7.5%, respectively. Coupling seems to be a sign of dysfunctional labor associated with a high incidence of abnormal deliveries, but several confounding variables could not be ruled out. PMID- 2905302 TI - Assessment of the glucose tolerance test in unselected pregnancy using 75 g glucose load. AB - A 75 g oral glucose tolerance test (OGTT) was performed in 618 unselected pregnant Chinese women between 24 and 28 weeks gestation. The glucose response at fasting, 1, 2 and 3 h were studied. At 2 h the glucose level at 2-standard deviation and 4-standard deviation above the mean came very close to the criteria of abnormality suggested by the World Health Organization (WHO): 8.3 mmol/l vs. 8.0 mmol/l for impaired glucose tolerance and 10.8 mmol/l vs. 11.0 mmol/l for gestational diabetes mellitus. The area under the glucose response curve also correlates best with the glucose levels at 2 h during the OGTT (y = 2.1x + 4.6, r = 0.885). The 75-g OGTT interpreted with the WHO criteria seems appropriate for pregnant Chinese women. The 75-g test has the added advantages of reducing administration cost and discomfort of the patients. PMID- 2905303 TI - The implications of childbearing in postpubertal girls in Sokoto, Nigeria. AB - A retrospective analysis of 337 young postpubertal delivered mothers was compared with other parturient women in Sokoto University Teaching Hospital (S.U.T.H.) during a 1-year period. In this analysis, late booking was identified as the most important factor that directly affects the perinatal outcome in young postpubertal pregnant mothers. The problems of postpubertal pregnancy were highlighted in order to motivate individuals towards family planning. PMID- 2905304 TI - Ovarian tumors in pregnancy. AB - Thirty-eight women were operated for an ovarian tumor diagnosed during pregnancy, with an incidence of 1/2328 deliveries. The diameter of all tumors was above 5 cm. Of the 31 women operated before delivery, seven were untreated and 24 received supportive progestational therapy. The rate of abortions was 85.7% in the untreated group and 10% in the hydroxy-progesterone-caproate group (HPC) (P less than 0.02). When the women received a total dose of HPC of more than 300 mg, 9 of 10 pregnancies reached term with a live child. Two ovarian malignancies were found, 5.3% of all cases. In 42.9% of the women there were fertility problems later in life. Ovarian tumors during pregnancy should be removed as soon as possible, irrespective of the age of the pregnancy. If fully progesterone therapy is given, the danger of abortions is reduced to a minimum. Prophylactic antibiotic treatment should also be administered. PMID- 2905305 TI - Criteria for the oral glucose tolerance test in pregnant and non-pregnant Nigerian women. AB - In order to establish diagnostic criteria for detection of abnormal oral glucose tolerance test (OGTT) in pregnant and non-pregnant Nigerian women, the test was performed in 25 non-pregnant and 60 pregnant non-diabetic women at various trimesters of pregnancy. The upper limit of normal plasma glucose was the same as that from caucasian populations with respect to the fasting values but much less at 60 and 120 min. When compared to the non-pregnant controls, fasting plasma glucose was significantly lower during pregnancy, however, there was no change in glucose tolerance during pregnancy. The possible reasons for these observations are discussed and it would appear that our criteria would be the ideal ones to use for clinical purposes in Nigerian women. PMID- 2905306 TI - Serum lactic dehydrogenase isoenzymes alteration in carcinoma cervix uteri. AB - Serum LDH-isoenzyme studies revealed that in carcinoma cervix, the principal activity was confined to LDH-2 and LDH-3 with a significant rise in LDH-2 fraction when compared with the control values (P less than 0.001). Radiotherapy caused significant lowering of LDH-2 and LDH-3 (P less than 0.001 in each case). There was no relation of LDH-isoenzyme distribution in different clinical stages and morphological distribution within the tumor. Further, LDH-2 and LDH-3 were found to be lowered significantly in good and moderate clinical radiation response (CRR) groups (P less than 0.001 in each case) but in poor CRR group no significant change in LDH-2 and LDH-3 was observed following radiotherapy. LDH isoenzyme determination in carcinoma cervix is very helpful in assessing the treatment response following radiotherapy and thus may be an important prognostic parameter. PMID- 2905307 TI - Experience with a new flexible hysteroscope. AB - This is a report of our experience with a new flexible fibroscope, the CHF P 10. We performed more than 50 diagnostic endoscopies and 28 operative procedures. It is extremely practical to perform diagnostic and operative procedures at the same time if necessary. The major advantages of the new fibroscope are its diameter (4.9 mm), flexibility and bendable tip (260 degrees range). This permits a substantial decrease in cervical dilatation and use of anesthesia. Because of this, hospitalization costs decrease and the safety of surgical procedures is increased. PMID- 2905308 TI - Expression of receptors, linked to cyclic AMP formation by cultures of human fetal astrocytes. PMID- 2905309 TI - Are post-mortem biochemical studies of human brain worthwhile? PMID- 2905310 TI - The use of renal cortical slices from the Fischer 344 rat as an in vitro model to evaluate nephrotoxicity. AB - The toxicity of several classical acute nephrotoxicants was evaluated in an in vitro system using renal cortical slices prepared from adult male Fischer 344 rats. Gentamicin, cephaloridine, 4-ipomeanol, potassium dichromate (K2Cr2O7), mercuric chloride (HgCl2), carbon tetrachloride (CCl4), and hexachlorobutadiene (HCBD) were preincubated with slices for 2 hr at 37 degrees C at concentrations ranging from 1 x 10(-6) to 1 x 10(-1) M. Following preincubation, slices were removed, rinsed in medium lacking the nephrotoxicant, and subsequently incubated for 90 min at 25 degrees C for physiological assessment of proximal tubular functions. Using a single preparation, slices were monitored for organic ion accumulation, gluconeogenesis, lipid peroxidation, and total glutathione (reduced and oxidized) concentrations. In addition, preincubation and incubation media were assessed for the presence of renal enzymes originating from brush border, cytosol, and lysosomes. The relative degree of toxicity in this model was consistent with nephrotoxic potency in vivo where HgCl2, K2Cr2O7 greater than HCBD greater than CCl4, cephaloridine greater than gentamicin greater than 4 ipomeanol. Effects on organic ion accumulation, gluconeogenesis, and glutathione concentrations occurred simultaneously for each toxicant. Toxicants produced different effects on enzyme release and malondialdehyde formation. These results suggest that toxicity produced in vitro is representative of in vivo nephrotoxicity and support the further use of this model to evaluate mechanisms of nephrotoxicity. PMID- 2905311 TI - Neuromuscular effects of chronic exposure to fenthion in dogs and predictive value of electromyography. AB - Chronic exposure to organophosphates (OP) can result in nonspecific neurologic signs in both man and animals. Improved methods are needed to predict toxicity and to better characterize neuromuscular effects. In this study, dogs were exposed to an OP (fenthion) by weekly dermal application of a 20% solution at a dosage of 44 mg/kg. This dosage does not produce signs of acute OP toxicity in dogs, although plasma cholinesterase (ChE) levels are significantly decreased. Electromyograms (EMG) were used to monitor motor unit potential (MUP) activity at minimal and submaximal contractile effort in four different muscles. At 1-month intervals, muscle biopsies were obtained and plasma ChE levels were determined. At 3 months, hyperreflexia and/or mild proprioceptive deficits were observed. The dosage was reduced to 22 mg/kg for the remaining 3 months of the study. At the end of this 6-month study, nerve and muscle biopsies were obtained. Mean plasma ChE levels were decreased (preexposure value of 1775 IU/liter to low of 310 IU/liter) and correlated with duration of exposure and change in dosage level. Fourier analysis of EMG indicated some increase in higher frequency components of the power spectrum with time, and analysis of individual MUPs revealed a significant (p less than 0.05) increase in the product of the amplitude times the duration of the potentials in all muscles examined. Biopsy results were supportive of EMG findings of altered neuromuscular function and loss of small motor units. The EMG changes were most consistent in the gastrocnemius muscle and were detected prior to development of clinical signs. These results indicate that EMG can be useful in monitoring OP exposure and predicting toxicity. PMID- 2905312 TI - [Medical treatment of hyperprolactinemic states using lisuride, a prolonged action dopaminergic]. PMID- 2905313 TI - [Mexican contributions to vaccines]. PMID- 2905314 TI - Partial linkage map of chromosome 13q in the region of the Wilson disease and retinoblastoma genes. AB - Genetic linkage maps are useful tools for defining the location of disease genes. Previously published maps of human chromosome 13 have been incomplete and have had ambiguities of order in the vicinity of the Wilson disease (WND) and retinoblastoma (RB1) genes. We have defined a six-locus map of this region using a large reference pedigree from Venezuela. Our map provides landmarks which will aid in the localization of WND, in determining the extent of deletions in retinoblastoma, and in the mapping of other marker loci. PMID- 2905315 TI - Expression of homeo box genes during mouse development: a review. PMID- 2905316 TI - polyhomeotic: a gene required for the embryonic development of axon pathways in the central nervous system of Drosophila. AB - Hypomorphic alleles of the locus polyhomeotic (ph) produce multiple, homeotic like transformations in adult flies that mimic dominant mutations in the Antennapedia and Bithorax complexes. Analysis of null alleles of ph has revealed a complex, embryonically lethal phenotype that includes cell death of the ventral epidermis and abnormalities in the patterns of expression of homeotic and segmentation genes. There is also a dramatic alteration in the pattern of axon pathways in the central nervous system, such that the wild-type array of segmentally repeated commissures and connectives is replaced by bundles of axons confined to the hemiganglia of origin. It is possible that this axonal phenotype is the result of loss of neuronal identity caused by abnormal homeotic and segmentation gene expression. PMID- 2905317 TI - Heat shock protein GroE of Escherichia coli: key protective roles against thermal stress. AB - An Escherichia coli mutant lacking the heat shock sigma-factor (sigma 32) is defective in transcription from heat shock promoters and cannot grow at temperatures above 20 degrees C. To assess physiological roles of sigma 32 and heat shock proteins, we isolated and characterized a set of temperature-resistant revertants from this deletion (delta rpoH) mutant. Most of them were found to carry a DNA insertion in the groE upstream region, resulting in high-level synthesis of major heat shock proteins GroE (GroES and GroEL). The levels of GroE produced varied in different revertants and correlated well with the maximum permissive temperatures; the highest GroE producers (approximately 10% of total protein) grew up to 40 degrees C but not at 42 degrees C. An additional mutation causing hyperproduction of DnaK (hsp70 homolog) was required for growth at 42 degrees C. Such effects of GroE and DnaK on the sigma 32-deletion strains were also confirmed by using multicopy plasmids carrying groE or dnaK. Thus, GroE plays a key protective role in supporting growth at normal physiological temperatures (20-40 degrees C), whereas high levels of DnaK are required primarily at higher temperature. PMID- 2905318 TI - 7-[125I]iodoclonazepam: purification by high-performance liquid chromatography for use in a very sensitive benzodiazepine radioimmunoassay of broad specificity. AB - The purification of 7-[125I]iodoclonazepam by high-performance liquid chromatography (HPLC) for use in a very sensitive benzodiazepine radioimmunoassay is described. A silica column is used with a non-aqueous eluent and sequential ultra-violet and gamma-ray detection. A commercially available antiserum is used at a dilution of 1:1000. Blood samples are diluted 10-fold with buffer before analysis and only 25 microliters of diluted sample are required per assay tube. Benzodiazepines, but not the radiolabel, appear to be bound by blood proteins in competition with the antiserum and so, if undiluted blood is assayed, erroneously low results are obtained. The minimal sample requirement and the high sensitivity of the assay described here largely avoid this problem while maintaining acceptable detection limits. For diazepam, the detection limit is 2.5 ng/ml in blood or urine (after correction for the initial 10-fold dilution) and therapeutic or sub-therapeutic levels of many other benzodiazepines can be detected. In practice, the assay is reliable, simple to perform and extremely economical. PMID- 2905319 TI - Postmortem stability of DNA. AB - High-molecular-weight DNA was recovered postmortem in sufficient quantities from various human organ tissues as well as from blood, although not all organs were equally well suitable. Good DNA stability was found in brain cortex, lymph nodes and psoas muscle over a period of three weeks postmortem. Spleen and kidney showed good DNA stability up to five days postmortem but after longer periods, rapid degradation was observed. Yields of DNA from blood were not consistent because of the non homogeneity of samples. Blood clots were rich with DNA. Generally, the amount of degraded DNA correlated directly with the duration of the postmortem period. However in some cases, DNA degradation was already prominent after a short period. However in some cases, DNA degradation was already prominent after a short period. Case histories showed that high environmental temperature at the site of death and/or infectious diseases prior to death were the main factors for rapid autolysis. Gradual disappearance to complete loss of the long fragments (15-23 kb) was observed in DNA fingerprinting using the minisatellite probe 33.15. No extra-bands were noted, thus excluding erroneous conclusions. However, evidentiary value of older samples was lower. PMID- 2905320 TI - [Effect of beta receptor blockers on the pressure tolerance of the optic nerve head]. PMID- 2905322 TI - [AIDS. Excessive decrease in T4 lymphocytes]. PMID- 2905321 TI - [Timolol, betaxolol and befunolol in the treatment of glaucoma. Study of their bronchopulmonary effects]. PMID- 2905323 TI - [Relinquishing reticence with regard to beta blockers]. PMID- 2905324 TI - [Guidelines for lipid-lowering therapy. Results of the 2d Consensus Conference of the European Atherosclerosis Society. Press conference. London, 6 May 1988]. PMID- 2905325 TI - [Lipid-lowering drugs]. PMID- 2905326 TI - [Diabetes and hyperlipidemia. Increased coronary risk can be prevented]. PMID- 2905327 TI - [Catalog of possibilities for decreasing coronary risk? Is the effort worth it?]. PMID- 2905328 TI - [What should lipid-lowering nutrition include?]. PMID- 2905329 TI - [Determine the cholesterol level early. Interview with Prof. G. Assmann, Munster]. PMID- 2905330 TI - [Guidelines for lipid-lowering therapy. Concrete references for diagnosis and therapy. Recommendations of the European Atherosclerosis Society expanded and defined]. PMID- 2905331 TI - [Stepwise diagnosis and therapy of hyperlipidemias]. PMID- 2905332 TI - [New trends in hypertension therapy. Scientific workshop. Munich, 4 March 1988]. PMID- 2905333 TI - [Effective combination in the therapy of hypertension. Prof. Dr. H. Brunner, Lausanne, elaborates on the advantages of a combination ACE inhibitor]. PMID- 2905334 TI - [Therapeutic breakthrough often only with combination therapy. An ACE inhibitor plus diuretics in the therapy of hypertension]. PMID- 2905335 TI - [Pharmacologic portrait of enalapril]. PMID- 2905336 TI - [Kidney protection by an ACE inhibitor]. PMID- 2905337 TI - [Tailoring therapy to the patient]. PMID- 2905338 TI - [Lowering blood pressure effectively. Enalapril and hydrochlorothiazide in fixed combination and mild and moderate hypertension--results of a multicenter study]. PMID- 2905339 TI - Integrating research projects into clinical service settings. PMID- 2905340 TI - Beta-blockade in acute myocardial infarction--a clinical perspective. PMID- 2905341 TI - Effects of different beta-blockers on lipid metabolism in chronic therapy of hypertension. AB - The aim of this study was to evaluate the possible time-related effects of long term monotherapy with different beta-blockers on plasma lipids in patients with essential hypertension. We studied 69 mild-moderate hypertensives, all males, aged 35-56 years belonging to the same working community. After 1-month placebo period, patients were assigned to receive propranolol 160 mg/day or atenolol 100 mg/day or bisoprolol 10 mg/day or mepindolol 10 mg/day. They were followed-up for 2 years. Blood pressure (BP), heart rate and blood samples for evaluation of total cholesterol (TC), LDL-cholesterol (LDL-C), triglycerides (TG) and HDL cholesterol (HDL-C) were taken before and after placebo period and every 6 months from the beginning of the active treatment. All beta-blockers caused similar reduction in BP values which persisted throughout the study. None of the beta blockers significantly affected TC and LDL-C. Propranolol caused the most pronounced changes in TG (+35-43%) and in HDL-C (-36-44%). Atenolol had the same qualitative effects but to a lesser extent (TG: +26-30%; HDL: -15-25%). Bisoprolol has more beta 1-selective than atenolol, and mepindolol, non-selective with ISA, increased TG (+15-28% and +13-23%) but did not significantly affect HDL C. Consequently, HDL-C and TG changes appeared to be related to the ancillary properties of the different beta-blockers and, in a lesser degree, to the duration of therapy. PMID- 2905342 TI - X-ray studies on crystalline complexes involving amino acids and peptides. XV. Crystal structures of L-lysine D-glutamate and L-lysine D-aspartate monohydrate and the effect of chirality on molecular aggregation. AB - L-Lysine D-glutamate crystallizes in the monoclinic space group P2(1) with a = 4.902, b = 30.719, c = 9.679 A, beta = 90 degrees and Z = 4. The crystals of L lysine D-aspartate monohydrate belong to the orthorhombic space group P2(1)2(1)2(1) with a = 5.458, b = 7.152, c = 36.022 A and Z = 4. The structures were solved by the direct methods and refined to R values of 0.125 and 0.040 respectively for 1412 and 1503 observed reflections. The glutamate complex is highly pseudosymmetric. The lysine molecules in it assume a conformation with the side chain staggered between the alpha-amino and the alpha-carboxylate groups. The interactions of the side chain amino groups of lysine in the two complexes are such that they form infinite sequences containing alternating amino and carboxylate groups. The molecular aggregation in the glutamate complex is very similar to that observed in L-arginine D-aspartate and L-arginine D-glutamate trihydrate, with the formation of double layers consisting of both types of molecules. In contrast to the situation in the other three LD complexes, the unlike molecules in L-lysine D-aspartate monohydrate aggregate into alternating layers as in the case of most LL complexes. The arrangement of molecules in the lysine layer is nearly the same as in L-lysine L-aspartate, with head-to-tail sequences as the central feature. The arrangement of aspartate ions in the layers containing them is, however, somewhat unusual. Thus the comparison between the LL and the LD complexes analyzed so far indicates that the reversal of chirality of one of the components in a complex leads to profound changes in molecular aggregation, but these changes could be of more than one type. PMID- 2905343 TI - L-tryptophan in neuroleptic-induced tardive dyskinesia. AB - Administration of the serotonin precursor L-tryptophan in a patient with neuroleptic-induced tardive dyskinesia, produced a dramatic reduction in the severity of the abnormal movements within 24 hours. This report supports our hypothesis that alterations in the function of serotoninergic neurotransmission are implicated in the pathophysiology of neuroleptic-induced tardive dyskinesia. PMID- 2905344 TI - Compound narcolepsy: development of biochemical imbalance. AB - In a review of existing literature, compound narcolepsy is shown to involve not only problems of sleep regulation, but also autonomic, hormonal, emotional, and possibly motor and cognitive dysfunctions, strongly implicating the hypothalamus, limbic system, and possibly the striatum and cortex in the disorder. Neurochemical studies and the pattern of narcoleptic symptoms support the idea of a dynamic imbalance between dopamine and acetylcholine in the etiology of the disorder. What is known about the natural history of compound narcolepsy suggests a developmental course beginning with fluctuations in dopamine release, followed by supersensitivity of dopamine autoreceptors, and later followed by a pattern of intrinsic oscillations and reciprocal "overshoots" in release of dopamine and acetylcholine to account for the typical sequence of appearance of narcoleptic symptoms. PMID- 2905345 TI - Population genetics of the globin genes in Polynesians. AB - Globin gene mapping data enable Polynesians to be divided into three distinct groups: (i) Maoris, Cook Islanders, (ii) Tongans, Samoans, (iii) Niue Islanders. Unusual RFLPs detected by the restriction enzymes Apa I and Bgl II are found in Polynesians. A high frequency of alpha-thalassemia in this population is explained by genetic drift and a founder effect. PMID- 2905346 TI - Homozygous beta zero-39 mutation with thalassemia intermedia in northern Sardinia: clinical, hematological and molecular analysis. AB - In this study, we investigated the clinical and hematological features and carried out alpha- and beta-globin gene analyses in 11 Sardinian adult beta zero thalassemia homozygotes from Northern Sardinia who were not transfusion dependent. Oligonucleotide analysis revealed in nine out of 11 patients the nonsense mutation at codon 39, which was associated either with haplotype II or IX (14/16 and 2/16 chromosomes, respectively). Haplotype II was linked to the A gamma T mutation. The G gamma globin level ranged from 50 to 70%. Four out of nine patients (44%) were heterozygous and 3/9 (33%) homozygous for the rightward deletional type of alpha-thalassemia; two (22%) had the normal alpha-gene complement. Patients who were alpha-thalassemia homozygotes (-alpha/-alpha) showed a more balanced globin chain synthesis ratio. This study confirms that alpha-thalassemia may ameliorate the clinical picture of homozygous beta zero thalassemia. PMID- 2905347 TI - The use of restriction fragment length polymorphisms for prenatal diagnosis: the estimation of diagnosable rate of multiple genetic markers and its use in detecting beta-thalassemia in a Chinese population. AB - As a codominant genetic marker, restriction fragment length polymorphism (RFLP) has been widely applied to the prenatal diagnosis of some genetic diseases. To evaluate the usefulness of the genetic markers in prenatal diagnosis, a parameter, the diagnosable rate or the proportion of diagnosable matings, is estimated when two or more genetic markers are used. The assessment is based on the distribution of haplotypes. By using the data of the distribution of haplotypes of beta-A (normal) and beta-T (beta-thalassemia) chromosomes in a Chinese population and the formula given, it is easy to calculate the different diagnosable rates of all the combinations of seven given genetic markers. The results could help us to find an appropriate combination of genetic markers in prenatal diagnosis and, therefore, makes it possible to obtain a sufficiently high diagnosable value with a limited number of genetic markers. PMID- 2905348 TI - Prenatal diagnosis of thalassemia: experiences at the Shanghai Children's Hospital. AB - Using DNA dot-blot hybridization, restriction endonuclease gene mapping with oligonucleotide probes, restriction fragment length polymorphism linkage analysis, and hybridization, prenatal diagnosis was performed for 32 pregnancies at risk for alpha-thalassemia and for 10 pregnancies at risk for beta thalassemia. The DNA samples were prepared from chorion villi or amniotic fluid cells. PMID- 2905349 TI - Cytogenetical investigations in patients with primary hyperparathyroidism and multiple endocrine neoplasia type 1. PMID- 2905350 TI - Amplification and overexpression of the P-glycoprotein genes and differential amplification of three other genes in SEWA murine multidrug-resistant cells. PMID- 2905353 TI - Temporomandibular joint evaluation and reconstruction. PMID- 2905351 TI - Histochemistry of nucleotidyl cyclases and cyclic nucleotide phosphodiesterases. PMID- 2905354 TI - Primary large B-cell malignant lymphoma. PMID- 2905352 TI - Organization of the guinea-pig uterine innervation. Distribution of immunoreactivities for different neuronal markers. Effects of chemical- and pregnancy-induced sympathectomy. AB - The structural organization of the guinea-pig uterine innervation was investigated by an immunofluorescence method using neurofibrillary protein (NF) and neuron-specific enolase (NSE) as general neuronal markers. NF- and NSE immunoreactive nerve trunks and non-varicose nerves formed continuous networks similar to nerves with analogue morphology and with immunoreactivities for tyrosine hydroxylase (TH; adrenergic nerves) and neuropeptide Y (NPY). NF- and NSE-immunoreactive non-varicose nerves occurred in the myometrium and along vessels, where TH- and NPY-immunoreactive varicose nerves were also comparatively frequent. After chemical sympathectomy all TH- and NPY-immunoreactive varicose nerves and most NF- and NSE-immunoreactive non-varicose nerves disappeared, suggesting colocalization of TH, NPY, NF and NSE immunoreactivities. During pregnancy all NF-, NSE-, TH- and NPY-immunoreactive nerve structures disappeared in the foetus-bearing uterine horns whereas in the cervix and non-foetus-bearing uterine horns only the myometrial TH- and NPY-immunoreactive varicose nerves disappeared. After parturition there was a complete structural restoration of all types of immunoreactive nerves in previously non-foetus-related tissue. The reinnervation of this tissue followed a similar time-course to that after chemical sympathectomy. In contrast, the reinnervation of previously foetus related tissue was much slower and incomplete. In conclusion, the whole autonomic uterine innervation undergoes overt structural changes during pregnancy and these changes are related to the foetus-bearing regions. PMID- 2905355 TI - Masquerading as coronary artery disease: idiopathic hypertrophic subaortic stenosis. PMID- 2905356 TI - A perspective on health benefits. Hypertension therapy. PMID- 2905357 TI - Intrabiliary rupture of hydatid liver cysts. PMID- 2905358 TI - Cough induced by enalapril and captopril. PMID- 2905359 TI - Effect of spider venom on cochlear nerve activity consistent with glutamatergic transmission at hair cell-afferent dendrite synapse. AB - Venom from the spider Argiope trifasciata, a highly specific blocker of the ionic channels associated with invertebrate glutamatergic receptors, was perfused through scala tympani of the basal turn of the pig cochlea. Its effect on spontaneous and driven activity of single afferent neurons was studied. 0.1 U/ml spider venom altered the maximum driven activity without an effect on spontaneous activity. 1 U/ml spider venom suppressed both spontaneous and driven activity. These findings are consistent with the hypothesis that L-glutamate is the neurotransmitter of the synapse between inner hair cells and primary auditory afferent neurons. The results also suggest that the differences in spontaneous activity between neurons may originate in variations in neurotransmitter release. PMID- 2905360 TI - Rhythmic discharge properties of caudal cochlear nucleus neurons during postnatal development in cats. AB - Action potentials recorded extracellularly from neurons within the caudal cochlear nuclei of developing cats exhibited distinctive temporal characteristics (i.e., rhythmic responses) in response to long-duration acoustic stimuli including both tone and noise bursts. Unlike the homogeneous response characteristics of auditory nerve fibers, cochlear nucleus neurons exhibited many variations in rhythmic discharge patterns. The majority of neurons within the caudal CN of kittens younger than 10 days of age responded rhythmically to long duration acoustic stimuli, however, the percentage of neurons responding rhythmically steadily decreased thereafter, and by the end of the second postnatal week most tonically-responding neurons maintained sustained steady state discharge rates throughout stimulation. Discharges of neurons recorded during the transitional ages (around 13 days) were rhythmic at low sensation levels and exhibited adultlike sustained patterns at higher levels. Using constant sensation level stimuli (re individual neuron thresholds), burst frequencies remained essentially constant during the period of development in which rhythmic responses were observed. Intervals separating discharge bursts decreased as stimulus intensities increased for all neurons studied during the relevant period, but were not related in an orderly way to stimulus frequency. The effects of intensity on response periodicity were not mimicked by altering the amount of neurotransmitter present at the postsynaptic cell through microiontophoresis of excitatory amino acids and their antagonists onto the surface of neurons within the caudal CN. In addition, some immature neurons which responded phasically to acoustic stimuli responded rhythmically during the simultaneous presentation of acoustic stimuli and neuroexcitatory agents (i.e., glutamate). These results suggest that the source of the rhythmicity is not intrinsic to neurons in the caudal CN. Based on these and other observations we conclude that the most probable source of response periodicity observed early in development is the domination of inner hair cell output by efferent projections of the olivocochlear bundle, the temporal discharge patterns of which are also periodic. PMID- 2905361 TI - Central nervous system control of airway tone in guinea pigs: the role of histamine. AB - The central nervous system (CNS) plays an important role in the reflex control of bronchomotor tone, but the relevant neurotransmitters and neuromodulators have not been identified. In this study we have investigated the effect of histamine. Anesthetized male guinea pigs were prepared with a chronically implanted intracerebroventricular (icv) cannula and instrumented for the measurement of pulmonary resistance (RL), dynamic lung compliance (Cdyn), tidal volume (VT), respiratory rate (f), blood pressure (BP), and heart rate (HR). Administration of histamine (2-30 micrograms) icv caused a significant (P less than 0.05) reduction of Cdyn with no change in RL, VT, and f. At a dose of 100 micrograms icv, histamine caused an increase in RL (202 +/- 78%), a reduction of Cdyn (77 +/- 9%), an increase in f (181 +/- 64%), and a reduction of VT (53 +/- 18%). There were no changes in BP and HR after 100 micrograms of icv histamine. In contrast, intravenous administration of histamine (0.1-2 micrograms/kg) caused a dose dependent decrease in Cdyn and increase in RL that was associated with tachypnea at each bronchoconstrictor dose. Intravenous histamine (2 micrograms/kg) produced a fall in BP and an increase in HR. The bronchoconstrictor responses to icv histamine were completely blocked by vagotomy and significantly reduced by atropine (0.1 mg/kg iv), whereas vagotomy and atropine did not block the bronchospasm due to intravenous histamine. Additional studies indicated that the pulmonary responses due to icv histamine (100 micrograms) were blocked by pretreatment with the H1-antagonist chlorpheniramine (1 and 10 micrograms, icv). These data indicate that histamine may serve a CNS neurotransmitter function in reflex bronchoconstriction in guinea pigs. PMID- 2905362 TI - Propranolol in the treatment of tardive akathisia: a report of two cases. AB - The authors present two patients suffering from tardive akathisia. They also review the available literature on the subject. Propranolol was found to be an effective treatment of tardive akathisia in both patients. The implications of this finding are discussed. PMID- 2905363 TI - Buspirone in the treatment of panic disorder: a controlled pilot comparison with clorazepate. PMID- 2905364 TI - Distribution of monoamine-synthesizing neurons in the human medulla oblongata. AB - We have employed immunohistochemical and morphometric procedures to study the distribution of monoamine-synthesizing neurons in the medulla oblongata of the adult human, utilizing antibodies to tyrosine hydroxylase (TH), phenylethanolamine N-methyltransferase (PNMT), and phenylalanine hydroxylase (PH8). In the human brain, the antigen with which PH8 reacts occurs within neurons that presumably synthesize serotonin (Haan et al., '87). Neurons containing these antigens were mapped and counted in successive coronal sections with the aid of a computer-assisted procedure. The results indicate that monoamine-synthesizing neurons are distributed in the human brain in patterns broadly similar to those described for other species. TH-immunoreactive cells extended caudorostrally for approximately 32 mm commencing at the spinomedullary junction and ending 8 mm caudal to the pontomedullary junction. In coronal sections these TH-immunoreactive neurons were seen in the lateral medulla dorsal to the inferior olive extending in a continuous band to the dorsomedial medulla. Above the obex the majority of these cells apparently synthesize adrenaline since many PNMT-immunoreactive cells were also found in this region. There were few or no PNMT-immunoreactive cells caudal to the obex, indicating that the TH immunoreactive cells in this region synthesize either noradrenaline or dopamine. Approximately 65% of these TH-immunoreactive neurons contained melanin pigment, whereas few or no PNMT-immunoreactive cells contained melanin pigment. PH8 immunoreactive cells extended throughout the rostrocaudal extent of the medulla oblongata (approximately 40 mm). In coronal sections the majority were found in the medullary raphe nuclei. However, many cells throughout the rostrocaudal extent of the medulla were found laterally intermingled with catecholamine synthesizing neurons. Occasional neurons in the lateral medulla appeared to contain both PH8- and TH-immunoreactivity. PMID- 2905365 TI - Neuronal localization of prosomatostatin mRNA in the rat brain with in situ hybridization histochemistry. AB - Individual neurons containing prosomatostatin mRNA were identified with in situ hybridization histochemistry. Our results demonstrate a widespread distribution of prosomatostatin mRNA in several regions of the rat central nervous system. Neurons containing this transcript were most abundant in the anterior olfactory nucleus, hypothalamus, hippocampus, and amygdala as well as in all regions of the cerebral cortex. Moreover, the distribution of mRNA-containing perikarya was coextensive with the location of neurons containing somatostatin-like immunoreactivity in all areas of the brain examined. Somatostatin neurons varied in their morphology and amount of hybridization signal from region to region. The widespread distribution and regional variations in neuronal morphology and the amount of hybridization signal are consistent with a neurotransmitter and/or a neuromodulator role for somatostatin in addition to its well-established neuroendocrine role. These results demonstrate that both the peptide and its mRNA are found in perikarya in the same areas and that they are therefore the sites of synthesis for somatostatin. PMID- 2905366 TI - Tissue activities of enzymes of diagnostic interest in the marmoset and rat. AB - The activities of enzymes of diagnostic interest were investigated in the liver, heart, kidney and muscle of the marmoset (Callithrix jacchus) and the rat. Methods of tissue extraction which gave maximal enzyme activity were used and comparison between the species showed some major differences. AST, LDH and GDH showed a similar distribution in both species but ICDH activity was much higher in the rat heart than in any other rat or marmoset organ. ALP, LAP and GGT were present in much higher activities in the rat kidney than in the marmoset kidney, a finding which was reversed in the liver of these animals. The major ALT containing organ in the rat was the liver but, in the marmoset, this enzyme was found in relatively large quantities in the heart and muscle also. These differences can be of importance when plasma enzyme activities are measured following tissue damage. PMID- 2905368 TI - Outbreak of infection with Achromobacter xylosoxidans from contaminated intravascular pressure transducers. AB - Achromobacter xylosoxidans contaminating transducers caused 15 cases of hospital infection. In the eight patients with bacteraemia the interval from inoculation to fever was an average of 6.6 days. All the infected patients recovered. Computerization of laboratory records allowed retrieval of previous isolates, and review of clinical records focused the problem on patients with cardiac and aortic diseases. The problem arose from the re-use of disposable equipment after disinfection with a benzalcone. PMID- 2905369 TI - Experience with Nocardia asteroides in renal transplant recipients. AB - Six cases of Nocardia asteroides infection in renal transplant recipients are described. Respiratory symptoms predominated, complicated in one case by cerebral abscess. General dissemination did not occur in any patient. Environmental testing failed to show source(s) of the organism. Nocardiosis patients should be isolated to prevent airborne spread to renal transplant recipients, who are prone to infection and from whom specimens for culture should be incubated for at least 7 days to exclude Nocardia spp. PMID- 2905367 TI - Neuroendocrine regulation of human growth hormone secretion. Diagnostic and clinical applications. PMID- 2905370 TI - Drug resistance and plasmid profiles in Staphylococcus epidermidis in 1964 and 1986. AB - An examination has been made of drug resistance and plasmid content of Staphylococcus epidermidis isolated from hospital patients in 1964 and 1986. Drug resistance was much more prevalent in isolates from 1986 than in isolates from 1964. Plasmids were demonstrated in 50 of 52 strains from 1964 and in 102 of 111 strains from 1986. The majority of both drug-sensitive and drug-resistant strains harboured more than one plasmid. Of five plasmids obtained from a multiply-drug resistant S. epidermidis, four were shown to mediate drug resistance. PMID- 2905371 TI - Cross-infection between animals and man: possible feline transmission of Staphylococcus aureus infection in humans? AB - An outbreak of epidemic methicillin-resistant Staphylococcus aureus occurred on a rehabilitation geriatric ward. Intensive screening of patients and staff revealed an unusually high carriage rate in the nursing staff (38%), thought to be related to a ward cat which was heavily colonized from the environment. Infection control measures and removal of the cat led to rapid resolution of the outbreak. PMID- 2905372 TI - Contamination of blood during cardiopulmonary bypass: the effect of antibiotic prophylaxis. AB - Despite antibiotic prophylaxis in cardiac surgery, gram-positive bacteria can be isolated in up to 10% of intraoperative blood cultures. During a prospective randomized trial, blood was collected from the oxygenator at the end of bypass in 58 patients given teicoplanin and in 60 others given flucloxacillin and tobramycin. Coagulase-negative staphylococci were cultured from 16 patients given teicoplanin but in only four cases after flucloxacillin and tobramycin (Fisher's exact test, P = 0.005). In contrast, Propionibacterium spp. or coryneforms were isolated from 22 patients given flucloxacillin and tobramycin and from only one patient in the teicoplanin group. There were no cases of prosthetic valve endocarditis. After 3 h exposure to 4 x MIC of teicoplanin there was only a 10-60 fold reduction in cfus of Staphylococcus epidermidis, which may partly explain the excess of these organisms. PMID- 2905373 TI - The effects of antiperspirant on the perineal skin flora of patients with spinal cord injury. AB - The relationship of pH and moisture to Pseudomonas aeruginosa and Klebsiella pneumoniae colonization of the perineal skin was studied in male patients with spinal cord injury. The increased pH of the perineal skin was significantly associated with the presence of P. aeruginosa but not other bacterial species. No correlation between colonization and moisture or pH and moisture was found. An antiperspirant produced a significant reduction in the number of total aerobic bacteria, total gram-negative bacilli, P. aeruginosa and K. pneumoniae over a 24 h period. Long-term use of the antiperspirant for 10 days did not alter the persistence of P. aeruginosa of the same serotypes on the perineum. PMID- 2905374 TI - Low-temperature washing of patients' clothing; effects of detergent with disinfectant and a tunnel drier on bacterial survival. AB - Patients' dresses were washed at 40 degrees C using an ordinary detergent for 1 week and a novel detergent with added 'Triclosan' for the following 2 weeks. The bacterial load on the finished laundry was acceptably low using either detergent. The killing of residual bacteria on washed clothing by drying in a tunnel finisher was demonstrated. This preliminary study did not show any benefits to be gained from the addition of 'Triclosan' to detergent for the low-temperature laundering of patients' clothing. PMID- 2905375 TI - A comparison of two bactericidal handwashing agents containing chlorhexidine. AB - The skin disinfectant properties of two handwashing agents containing chlorhexidine, 'Uniscrub' and 'Hibiscrub', have been compared. The two products were assessed according to their ability to remove both transient organisms and natural or resident bacteria from the skin. They were found to be equally effective as antibacterial hand disinfection agents. PMID- 2905376 TI - Re-usable ECG electrodes--a vehicle for cross-infection? PMID- 2905377 TI - Value of bacteriological screening specimens in the diagnosis and management of neonatal infection. PMID- 2905378 TI - Septic complications following endoscopic retrograde cholangiopancreatography: the experience in Tel Aviv Medical Center. AB - At the Tel-Aviv Medical Center, five of 720 (0.69%) patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) subsequently developed septicaemia. One of these patients (0.14%) died as a direct result and three other septicaemic patients died from other complications. The most important risk factor associated with infectious complications was obstructive jaundice. Retrospective analysis of our data revealed that no cases of septicaemia developed in patients given prophylactic antibiotics, whereas 4.3% of patients who received no prophylactics developed infectious complications. Prophylactic antibiotics are therefore recommended for patients undergoing ERCP who have biliary obstruction. PMID- 2905379 TI - The somatotrope: an endocrine cell with functional calcium transients. AB - Growth hormone (GH) secretion by the somatotrope is under dual regulation by the hypothalamic peptides, somatostatin (SS) and GH-releasing hormone (GHRH). Cytosolic free calcium concentration and cumulative GH release were measured simultaneously in anterior pituitary cells from adult male rats. This was made possible using a combination of digital imaging video microscopy with the fluorescent calcium indicator Fura-2 and the reverse haemolytic plaque assay (RHPA) to identify the cell type and measure hormone secretion from the cells under study. This technique allows calcium measurements to be made at very short time intervals (less than 150 ms) in single cells. Spontaneous calcium transients were demonstrated in 85% of GH plaque-forming cells. These occurred at a frequency of 2-13 min-1 and had an amplitude of 50-500 nmoll-1. The somatotropes with the largest calcium fluctuations produced the largest plaques; thus, the calcium transients appeared to correlate with hormone release. Since the somatotrope alone shows these fluctuations, the mean intracellular calcium concentration is 238 +/- 18 nmoll-1 in somatotropes and 113 +/- 8 nmoll-1 in non somatotropes. Upon exposure to SS (1 nmoll-1) intracellular calcium fell from 200 250 nmoll-1 to 50-100 nmoll-1 with an apparent reduction in oscillations. Withdrawal of SS increased the intracellular calcium level. GHRH increased intracellular calcium but 10 nmoll-1 GHRH given simultaneously with 1 nmoll-1 SS reduced intracellular calcium to that level observed during SS alone. Thus, the SS effect on intracellular calcium predominates. The effects of SS can be mimicked by removal of extracellular calcium, or by the addition of CoCl2 (2 nmoll-1) or by verapamil (100 mumoll-1), two agents which block calcium channels. The hormone secretion index (indicated by the area of the plaque formed in RHPA) enables us to demonstrate that GHRH in this system increases GH secretion, and SS inhibits it. In combination, GHRH and SS oppose one another. Spontaneous calcium oscillations are characteristic for normal somatotropes. These oscillations are related to spontaneous hormone secretion and due to influx of calcium through ion channels in the membrane. Intracellular signalling information may be encoded in both frequency and amplitude of calcium oscillations. The actions of GHRH and SS on regulation of GH secretion are proposed to be mediated, at least in part, by regulation of intracellular cytosolic free calcium. This modulation is dependent on extracellular calcium concentrations. We are now investigating the molecular mechanisms involved in this process. PMID- 2905380 TI - Systemic phenoxybenzamine but not beta-adrenergic antagonists block noradrenergic inhibition of cerebellar Purkinje and hippocampal pyramidal neurons. AB - Previous pharmacological characterization of central noradrenergic receptors has been interpreted as favoring beta-type receptors on cerebellar Purkinje neurons and hippocampal pyramidal neurons. However, the recent development of additional noradrenergic antagonists suitable for single neuron analysis, prompted an initial re-evaluation of alpha and beta adrenergic receptors in these two cell populations. In contrast with earlier data based on local antagonism of iontophoretric or synaptically released norepinephrine (NE), we now find that systemic phenoxybenzamine, the alpha antagonist, was effective in blocking responses to NE in cerebellum and hippocampus, whereas systemic beta antagonists metoprolol, ICI 118.551 [correction of ICI 181.551], or proprandol did not interfere with local NE responses at systemic doses that altered spontaneous discharge rates. These preliminary data suggest that a more complete re evaluation of the nature of central noradrenergic response mechanisms may be warranted. PMID- 2905381 TI - Effect of benzodiazepines on the proliferation of mouse spleen lymphocytes in vitro. AB - The effect of several benzodiazepines (clonazepam, diazepam, Ro 5-4864, Ro 15 1788) and two pineal gland indoleamines (N-acetylserotonin, melatonin) on the spontaneous proliferation of mouse spleen lymphocytes was estimated in vitro by the 3 H-thymidine uptake assay. It was found that diazepam and Ro 5-4864 (a selective peripheral-type benzodiazepine receptor ligand) produced the concentration-dependent inhibition of 3 H-thymidine incorporation into the DNA of these cells. Ro 15-1788, a specific central-type receptor ligand, evoked a slight inhibitory effect in a high concentration (10(-4) M), whereas clonazepam did not produce any significant inhibition. When Ro 5-4864 was tested in combination with diazepam, the inhibition of lymphocyte proliferation did not exceed the effect of diazepam given alone. Ro 15-1788 was unable to reverse the inhibitory action of diazepam in the same experimental conditions. Melatonin and its precursor N acetylserotonin tested in the concentration range of 10(-4)-10(-8) M had no significant influence on the spleen lymphocyte DNA replication in our assay system. These data suggest that diazepam inhibition of lymphocyte proliferation is mediated by peripheral-type sites. Additionally, the fact that melatonin and N acetylserotonin were unable to affect 3 h-thymidine incorporation argues against any benzodiazepine receptor mediated effect of pineal indoleamines on a cellular proliferation. PMID- 2905382 TI - Adrenergic, serotoninergic, histaminergic, and imipramine binding sites in post mortal human cerebral microvessel preparations. AB - Cerebral microvessels were prepared from fresh and frozen human brain samples obtained from autopsy cases. Structural integrity and purity of the microvessels were confirmed by light and electron microscopy, and by measurement of the enzymatic marker gamma-glutamyltranspeptidase. Similar morphological and enzymatic characteristics were found for the microvessels prepared from fresh and frozen brain samples. Radioligand binding experiments indicated the presence both in the "fresh" and "frozen" microvessel preparations of specific alpha 1-, alpha 2-, and beta-adrenergic, histamine H1, serotonin S1 and imipramine binding sites, although the density of beta-adrenergic and histamine H1 specific binding sites were lower in the frozen samples than in the fresh samples. Low levels of specific binding to muscarinic, GABAergic and serotonin S2 sites (with respect to the specific binding densities in the crude homogenates) were found in the microvessel preparations. PMID- 2905383 TI - Effect of clonidine on ultrasonic vocalization in preweaning rats. AB - The present study was undertaken to investigate the involvement of the noradrenergic neurotransmission system in the ultra sonic callings emitted by rat pups separated from their mother and exposed to cold stimulation. The investigation was primarily performed by help of agents selectively affecting the alpha-adrenoceptors: the alpha 2-agonist clonidine, the alpha 1-antagonist prazosin and the alpha 2-antagonist idazoxan. Clonidine dose-dependently stimulated the amount of ultra sonic vocalization, an effect not solely dependent upon the effect of clonidine on body temperature. In a developmental study it was found that clonidine uniformly stimulated crying at all ages from 4 days of age up to 18 days of age, that is during the whole preweaning period. Clonidine stimulated ultrasonic crying in rat pups, devoid of presynaptic catecholamine (CA) neurons by combined pretreatment with the monoamine depletor, reserpine, and the inhibitor of CA-synthesis, alpha-methyl-tyrosine. This finding suggested that the stimulating effect of clonidine on ultrasonic vocalization was mediated by postsynaptic adrenoceptors. In pups, 12 days of age, idazoxan blocked the effect of cold stimulation on ultra sonic crying, suggesting that alpha 2-adrenoceptors, presumably postsynaptic ones, mediated this kind of stimulation. Idazoxan also antagonized the effect of clonidine, but only at a dose effective also in control pups. Prazosin had no effect on cold-stimulated crying, but antagonized the effect of clonidine, suggesting that the effect of clonidine was also mediated by alpha 1-receptors. At 18 days of age, prazosin no longer antagonized the effect of clonidine, whereas the antagonizing action of idazoxan was reinforced. The age dependent variation in responsiveness to the adrenergic drugs suggest maturational changes in the function of the CA-system occurring between 12-16 days of age. PMID- 2905384 TI - An adult onset metachromatic leukodystrophy with dominant inheritance and normal arylsulphatase A levels. AB - A family with a variant of adult onset metachromatic leukodystrophy is presented. Clinical details from three affected members are given. The neurophysiological and neuroradiological data on the two brothers who have been recently studied are included. One of these died and the post-mortem findings are discussed along with those from a cousin who died some years ago. Arylsulphatase A levels were normal in both brothers yet the histological findings in the one who died are of a metachromatic leukodystrophy and thin-layer chromatography confirms an excess of sulphatides in the white matter of his brain. Disabling hypotension was a striking feature in both brothers but adrenal function was shown to be intact and autonomic neuropathy seemed the likely cause. Study of the family suggests a dominant mode of inheritance. PMID- 2905385 TI - Somatostatin concentrations and binding sites in human frontal cortex are differentially affected in Parkinson's disease associated dementia and in progressive supranuclear palsy. AB - Somatostatin (SRIF) binding sites were characterized in membrane preparations from post mortem human brain tissues using 125I-Tyr0-D-Trp8-SRIF as a ligand. Density of binding sites were high in subiculum and cortex, moderate in temporal cortex, hippocampal formation and hypothalamus and low in putamen. No correlation was observed with the regional distribution of SRIF levels as measured by RIA. Pharmacological characterization, in frontal cortex preparations, revealed that 125I-Tyr0-D-Trp8-SRIF binding was heterogenous and fitted best with a two sites model. 125I-Tyr0-D-Trp8-SRIF binding was guanine nucleotide dependent. Cortical 125I-Tyr0-D-Trp-8-SRIF binding was not different from controls in non-demented or demented parkinsonians and in patients with progressive supranuclear palsy. On the contrary, SRIF levels were significantly decreased in demented parkinsonians. PMID- 2905386 TI - In situ hybridization of mRNA for beta-preprotachykinin and preprosomatostatin in adult rat dorsal root ganglia: comparison with immunocytochemical localization. AB - In situ hybridization histochemistry was used to identify neurons in rat dorsal root ganglia that contained mRNAs encoding beta-preprotachykinin and preprosomatostatin. The distribution of these neurons was compared with the distribution of neurons containing tachykinins or somatostatin, identified using immunocytochemical techniques. Neurons labelled for beta-preprotachykinin mRNA constituted 20% of the total neuronal population and belonged to the small cell class. Neurons labelled for preprosomatostatin mRNA with either RNA or DNA hybridization probes constituted approximately 10% of the total cells and comprised a small cell group that differed in average size from the beta preprotachykinin labelled population. The distribution of cells containing tachykinin- or somatostatin-like immunoreactive material was identical to the distribution of cells containing the respective mRNAs and, in addition, individual somata in adjacent sections contained both the mRNA precursor and the peptide. These results suggest that for these neuropeptides the sensitivity of the two methods is equivalent and the respective mRNAs and peptides are co localized in the same neurons. PMID- 2905387 TI - Rationale and design of a randomized clinical trial on prevention of stroke in isolated systolic hypertension. The Systolic Hypertension in the Elderly Program (SHEP) Cooperative Research Group. AB - Isolated systolic hypertension (ISH)--i.e. high systolic pressure with nonhypertensive (less than 90 mmHg) diastolic pressure--is a recognized risk factor for cardiovascular disease among individuals in the age group 60 years and above. This observation suggests that antihypertensive treatment might be beneficial. Results of the Systolic Hypertension in the Elderly Program Pilot Study (SHEP-PS) indicated the feasibility of a full-scale clinical trial on the efficacy of drug treatment of ISH. The Systolic Hypertension in the Elderly Program (SHEP) is a randomized, double-blind, placebo-controlled clinical trial with the primary objective of assessing the effect of drug treatment of ISH- systolic pressure 160-219 mmHg and diastolic pressure less than 90--on occurrence of fatal and nonfatal stroke. This multicenter clinical trial has a sample size of 4736 participants, with high statistical power to detect a reduction of 32% or more in the study's primary end point during the 4-6 year period of treatment and follow-up. Low dosage chlorthalidone is the main study drug. Further features of the design of SHEP and the trial's organization are described. PMID- 2905388 TI - Cyclic nucleotide metabolism in pineal homogenates. AB - Adenylate cyclase (AC) in pineal particulate fractions from rabbit, rat, cow, and the vole Microtus montanus was stimulated by L-norepinephrine (NE) and L isoproterenol (ISO). NE stimulation of rabbit and bovine pineal AC was biphasic, with a plateau between 0.01 microM and 1.0 microM and additional stimulation by NE above 1.0 microM. Stimulation by different ISO concentrations gave a typical hyperbolic curve, and optimal stimulation by ISO exceeded that by NE. Melatonin decreased ISO and NE stimulation of AC 10-20%. Although, alpha-adrenergic agonists increase beta-agonist-mediated adenosine-3',5'-cyclic monophosphate (cyclic AMP) accumulation in intact pinealocytes, similar amplification of AC stimulation was not seen with broken-cell preparations. Most (60-70%) pineal guanylate cyclase (GC) was recovered in supernatant fractions after centrifugation of homogenates at 110,000 x g; this soluble GC was unaffected by potential agonists. Low concentrations (0.01-1 nM) of NE, ISO, and phenylephrine (PE) stimulated GC in impure and purified membrane fractions, but each inhibited at concentrations above 10 microM. All concentrations of ISO and NE inhibited GC in the presence of the alpha-agonist PE. Melatonin alone did not affect particulate GC, but L-ISO stimulation was not seen in the presence of equivalent concentrations of melatonin. The in vitro data are consistent with both alpha- and beta-receptor regulation of cyclic nucleotide metabolism in pinealocytes. Endogenous NE may differentially regulate cyclic AMP and guanosine-3',5'-cyclic monophosphate (cyclic GMP) in pineal; low NE concentrations that stimulate GC have only a slight effect on AC, but higher NE concentrations that inhibit GC maximally stimulate AC. Particulate GC and AC also were resolved by equilibrium centrifugation, to give several discrete peaks of enzyme activity. The results support the existence of several forms of AC and GC, which have different responses to adrenergic agonists. PMID- 2905389 TI - Identification by heteroduplex analysis of an invertible element (Min) common among IncM group plasmids. AB - The analysis of heteroduplexes between EcoRI digested DNA derived from IncM plasmids in the transfer-off and in the transfer-on state revealed an internal loop of about 1 kbp on a distinct large EcoRI fragment. The presence of an invertible element (Min) is suggested which enables the formation of conjugative pili at 30 degrees C, but switches off the pilus formation at 37 degrees C incubation temperature. PMID- 2905390 TI - Guanylate cyclase activation by organic nitrates is not mediated via nitrite. AB - Nitrovasodilators relax vascular smooth muscle by stimulating guanylate cyclase. Ignarro et al. (1981) proposed a mechanistic scheme according to which organic nitrates release nitrite in the presence of thiols. The corresponding nitrous acid would decay leading to nitric oxide, which then would react with another thiol to nitrosothiol. Dose-response relations with regard to guanylate cyclase stimulation of organic nitrates and sodium nitrite were compared in the presence of cysteine and its closely related methylester. Nitrite formation from ED95 concentrations of organic nitrates was also measured and compared with that present under an equi-effective concentration of sodium nitrite. In addition, the proposed formation of nitrosothiol from nitric oxide was re-examined. In the presence of cysteine, organic nitrates as well as sodium nitrite stimulated guanylate cyclase, but nitrite formation under ED95 concentrations of organic nitrates was 1000-fold smaller than that present under an equi-effective concentration of sodium nitrite. In the presence of cysteinemethylester, liberation of nitrite from organic nitrates was similar but no stimulation of guanylate cyclase was obtained. Sodium nitrite, however, showed a stimulating activity similar to that in the presence of cysteine. These results clearly demonstrate that guanylate cyclase stimulation by organic nitrates is not mediated by nitrite and subsequent formation of nitrosothiol. Since nitrous acid did not decay to nitric oxide in the pH range studied, the formation of nitrosothiol is apparently due to a direct reaction of nitrous acid with thiol. PMID- 2905391 TI - Gizzard ulceration in chicks fed cysteamine alone or in combination with a histamine H2-receptor antagonist. AB - A study was carried out to evaluate the effect of cysteamine-HCl administration on gizzard ulceration and growth performance in broiler chicks. The effectiveness of the histamine H2-receptor antagonist, SKF 93479, in preventing gizzard ulcerations when given in combination with cysteamine-HCl was also examined. In the initial experiment cysteamine-HCl at the level of 2400 mg/kg of the diet caused severe gizzard ulceration and mortality and decreased feed intake and growth in chicks. The effect was not seen when cysteamine-HCl was administered at 600 or 1200 mg/kg of the diet. In Experiment 2 broiler chicks administered cysteamine-HCl at 1800 mg/kg of the diet had an increased incidence of gizzard ulceration and decreased growth performance. The severity of gizzard lesions and the depression of growth performance were not as great as in the group in Experiment 1 which received the 2400 mg/kg level of cysteamine-HCl. Addition of the H2 antagonist SKF 93479 at 54 mg/kg of the diet had no effect on improving gizzard ulcer score or growth performance in chicks which received cysteamine-HCl at the 1800 mg/kg of the diet level. From these data it appears that the administration of ulcerogenic levels of cysteamine-HCl in the chicken may involve a more complex pathogenesis in which factors other than acid hypersecretion are involved. PMID- 2905392 TI - Effects of selective alpha 1-adrenoceptor blockade in dogs with hypoxic pulmonary vasoconstriction. AB - The acute effects of the selective alpha 1-blocker, E-643 (Bunazosine), on experimental pulmonary hypertension (PH) caused by hypoxic pulmonary vasoconstriction (HPV) in mongrel dogs were examined. Ninety second ventilation with 5% O2 and 95% N2 was used for hypoxic stimulation. The effects of E-643 were evaluated at doses of 1, 5, 10, 20 and 50 micrograms/kg in this order until the systemic arterial mean pressure (SAm) had decreased by 20 mmHg when compared with the control value during room air ventilation. PaO2 and PaCO2 decreased by 64.6 +/- 11.0 Torr and 2.4 +/- 2.5 Torr, respectively, and the pH increased by 0.031 +/- 0.012 during hypoxic ventilation. These blood gas changes affected during hypoxic stimulation were almost the same before E-643 administration. Progression of arterial blood hypoxemia due to E-643 administration during room air ventilation was not observed. SAm decreased by 8.0 +/- 11.9 mmHg after E-643 administration, while left atrial mean pressure (LAm) and cardiac output (CO) did not change significantly. Prior to E-643 administration, mean pulmonary arterial pressure (PAm) and pulmonary vascular resistance (PVR) increased by 6.4 +/- 3.3 mmHg and 6.2 +/- 3.8 HRU, respectively, during the 90 sec hypoxic ventilation period. After E-643 administration, the increases in PAm and PVR were 3.9 +/- 1.7 mmHg and 3.3 +/- 2.3 HRU, respectively. The suppression of increases in PAm and PVR was significant. The conclusion is that E-643, a selective alpha 1-blocker, is effective at restraining HPV in the dog model. PMID- 2905393 TI - A comparative study of the effects of four choline esters on the secretion of fluid and glycoprotein from rat submandibular glands. AB - The actions of four choline esters, acetylcholine (ACH), methacholine (MET), carbachol (CAR) and bethanechol (BET), on the secretion of saliva and the specific glycoprotein (GP) contained in the secretory cells of the submandibular gland (SMG) of the rat were compared under conditions with and without physostigmine (PHY). The ED50 values with respect to salivation were 17 mg/kg for ACH, 1060 micrograms/kg for BET, 810 micrograms/kg for MET and 75 micrograms/kg for CAR, whereas after pretreatment with PHY, ED50 values were lowered to 7.5 mg/kg for ACH and 212 micrograms/kg for MET, but remained unchanged for CAR and BET. SDS-polyacrylamide gel electrophoresis demonstrated that the saliva from the SMG elicited by the four choline esters contained GP I (130 KDa) and GP IV (21.5 KDa), characteristic of the acinus, and a band of GP III (31 KDa), which originates from the granular tubules. The order of intensity of these bands was band I much greater than band III = band IV. Among these bands, band I increased in intensity in a dose-dependent manner. These results suggest that the four choline esters act mainly on the acinar cells, but exert some effects on the granular tubules of the rat SMG. PMID- 2905395 TI - Spermatogenic function and fertility in unilateral cryptorchid dogs after orchiopexy and contralateral castration. PMID- 2905394 TI - Investigations into the mechanism of the antihypertensive effect of SGB-1534, a novel alpha 1-adrenoceptor antagonist, in rats. AB - Experiments in vitro and in vivo were undertaken to examine possible involvement of a central effect in the hypotensive mechanism of SGB-1534. SGB-1534 selectively antagonized the contraction of isolated rat aortae to phenylephrine with a pA2 value of 10.57, 3.9 times higher than prazosin, and markedly displaced the alpha 1-adrenoceptor ligand 3H-prazosin (pKi: 8.81) in rat brain. In anesthetized spontaneously hypertensive rats (SHRs), SGB-1534 (0.3-3 micrograms/kg) and prazosin (3-30 micrograms/kg) given intravenously (i.v.) and intracerebroventricularly (i.c.v.) produced a dose-dependent and long-lasting depressor response associated with no change in heart rate (HR). The two drugs (i.c.v.), however, significantly attenuated the pressor response to i.v. noradrenaline. Single i.v. injections of SGB-1534, prazosin and yohimbine dose dependently inhibited the St 587 (a highly specific and centrally acting alpha 1 adrenoceptor agonist) enhanced flexor reflex and the pressor response to i.v. phenylephrine in pithed rats. However, the activities of SGB-1534 and prazosin in inhibiting the St 587-enhanced flexor reflex were 16,000 and 660 times, respectively, less than those in attenuating the pressor response to i.v. phenylephrine. It seems that the hypotensive action of SGB-1534 is due to the peripheral alpha 1-adrenoceptor antagonistic mechanism rather than the central one. PMID- 2905396 TI - Isolation of fecal Clostridium perfringens from broiler chickens and their susceptibility to eight antimicrobial agents for growth promotion. PMID- 2905397 TI - Virulence of wild-type E. coli uroisolates in experimental pyelonephritis. AB - This study was designed to analyze the colonizing and invasive properties of wild type bacteriuric E. coli possessing a variety of phenotypic characteristics in experimental nonobstructive pyelonephritis (P and Type 1 [T] fimbriae, hemolysin [Hly], presence of K capsules, flagella [H], serotype, biotype, human and mouse serumcidal resistance). Special emphasis was on the role of Gal-Gal adhesin (P fimbriae) of non-genetically engineered uroisolates. It was shown that organisms that are P+ or T+ or Hly+ are more likely to colonize bladders than strains negative for those parameters (P less than 0.001). Additionally, P+ strains were more often associated with kidney histopathology than P- E. coli (P less than 0.05). However, the data also indicated that fimbriae (P and Type 1) were not sole determinants of virulence since two strains devoid of fimbriae, hemolysin, K capsules and sensitive to human serumcidal activity caused incipient and acute pyelonephritis. Even among identical serotypes and biotypes, the presence/absence of fimbriae did not appear to be the critical factor in urovirulence, nor did the presence of several positive characteristics (hemolysin, K capsule, flagella, serum resistance) in a given strain enhance uropathogenicity. Therefore, these properties do not need to work together to render an E. coli urovirulent. These phenotypic characters may simply represent associated or serologic markers with the host serving as the dominant determinant of susceptibility to urinary infection. The findings emphasize the inherent limitations in relating and extrapolating colonizing and invasive properties of genetically engineered strains to those of naturally occurring, wild-type E. coli human uroisolates causing pyelonephritis. PMID- 2905398 TI - [European nursing conference of the WHO in Vienna]. PMID- 2905399 TI - [Annual meeting of the European Nursing Students Group 1988 in Berne, Switzerland]. PMID- 2905400 TI - DNA technology in diagnosis and treatment. PMID- 2905401 TI - [Effects of intravenous administration of fenoldopam on blood pressure and renal function in severe arterial hypertension]. PMID- 2905402 TI - [Treatment of acromegaly]. PMID- 2905403 TI - [Glafenine hepatotoxicity]. PMID- 2905405 TI - [Hazards of iodinated contrast media and their prevention]. PMID- 2905404 TI - [Glafenine hepatotoxicity or acute cardiac liver?]. PMID- 2905406 TI - Demonstration of beta 1-adrenoceptor mediating relaxation of porcine coronary artery by radioligand binding and pharmacological methods. AB - beta-adrenoceptors in the porcine coronary artery were characterized by a radioligand binding assay using (-)-[3H]dihydroalprenolol (DHA) and also by measuring the relaxant response of isolated coronary artery to norepinephrine. Specific (-)-[3H]DHA binding in the porcine coronary artery was saturable, reversible and of high affinity (Kd = 1.6 nM) with a maximal number of binding sites of 63 fmol/mg protein, and it showed a pharmacological specificity as well as stereoselectivity which characterized beta-adrenoceptors. The Hofstee analysis of inhibition of (-)-[3H]DHA binding by atenolol, practolol and ICI 118551 has shown that the averaged concentration of beta 1 and beta 2-adrenoceptors in this tissue was 68% and 32% respectively. The relaxant response of isolated coronary artery to norepinephrine was competitively antagonized by (-)propranolol, (+)propranolol, atenolol, practolol and ICI 118551. The pA2 values of these adrenoceptor antagonists were significantly correlated with the Ki values for beta 1 but not beta 2-adrenoceptors determined by the (-)-[3H]DHA binding assay. Thus, the present study demonstrates that the relaxant response of porcine coronary artery to norepinephrine is predominantly mediated through the stimulation of beta 1-adrenoceptors on vascular smooth muscles. PMID- 2905407 TI - The differential effects of alpha 2-adrenergic stimulation on the myocardium and coronary vessels in the isolated rat heart. AB - The differential effects of alpha 2-adrenoceptor stimulation on myocardial contractility and coronary circulation were examined in the isolated perfused rat heart. We studied 20 Sprague-Dawley rats of similar age (26-28 weeks) and body weight (500-550 gm). Myocardial contractility (LV +dp/dt and developed pressure, LVP) and coronary flow resistance (CFR) were tested in the isolated isovolumic hearts using Langendorff preparation at a constant perfusion rate (2.5 ml/min/100 g BW) of Krebs-Henseleit bicarbonate solution. Group I (N-7) received B-HT 920 (specific alpha 2-adrenergic agonist, 0.6 to 58 micrograms/min), Group II (N-7) received B-HT 920+Yohimbine (300 nM in the perfusate). Group III (N-6) received vehicle only. Baseline LVP, LV +dP/dt and CFR were not significantly different among the 3 groups. During drug or vehicle administration, LVP and LV +dP/dt remained unchanged in all the groups. Coronary flow resistance increased in a dose-response fashion with a maximum increase of 22.7 +/- 3.6 (SE) mmHg/ml/min/g LV in Group I, and 10.5 +/- 2.0 mmHg/ml/min/g LV in Group II (p less than 0.02). We conclude that in the Sprague-Dawley rat heart, the physiologic effects of alpha 2-adrenoceptors are predominant in the coronary circulation but not in the myocardium itself possibly because of absence of post-synaptic alpha 2-adrenergic receptors in the rat myocardium. PMID- 2905408 TI - Effect of dietary alpha-linolenate/linoleate balance on mean survival time, incidence of stroke and blood pressure of spontaneously hypertensive rats. AB - Following the suckling period, stroke-prone spontaneously hypertensive rats (SHR SP) were fed semi-purified diets supplemented either with safflower seed oil (rich in linoleic acid) or with perilla seed oil (rich in alpha-linolenic acid). The mean survival time of male SHR-SP fed the perilla diet was longer than that fed the safflower diet by 17% (p less than 0.001) while the difference was 15% in female SHR-SP (p less than 0.05). The mean survival times of female SHR-SP were more than 40% longer than those of male SHR-SP in both dietary groups. Post mortem examinations of brains revealed apoplexy-related symptoms as the major cause of the death in both dietary groups. The systolic blood pressure was lower by ca. 10% (21 mmHg) in the perilla group than in both the safflower group and conventional diet group. The eicosapentaenoate (20:5 n-3)/arachidonate (20:4 n-6) ratio of platelet phospholipids in spontaneously hypertensive rat (SHR), a measure of platelet aggregability, was much higher in the perilla group than in the safflower group. Thus, increasing the dietary alpha-linolenate/linoleate ratio resulted in an increased mean survival time of SHR-SP rats, possibly by lowering blood pressure and platelet aggregability. PMID- 2905409 TI - Different effects of intracerebral and systemic administration of buspirone in the forced swimming test: involvement of a metabolite. AB - Buspirone, a drug with high affinity for serotonin1A receptors, was studied for its ability to reduce rats' immobility in the forced swimming test when injected systemically or into the nucleus raphe dorsalis (DR). Between 0.1 and 10 mg/kg buspirone had no effect on rats' immobility when injected systemically as a single dose or as a 3-injection course during 24 hours. Direct injection of 1 and 5 mu/0.5 microliter buspirone in the DR significantly reduced the duration of immobility without changing rats' activity in an open field. The anti-immobility effect of 1 microgram/0.5 microliter buspirone in the DR was completely prevented by injecting 2.5 micrograms (-)-propranolol in the same area. Oral administration of 0.3-1.0 mg/kg 1-(2-pyrimidinyl)piperazine (1-PP), one of the main metabolites of buspirone, and 0.3-3.0 mg/kg s.c. idazoxan, two substances with alpha 2 adrenergic blocking properties, completely antagonized the effect of 0.25 mg/kg s.c. 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), an agent with selective affinity for serotonin1A receptors. The anti-immobility effect of an infusion of 1 microgram/0.5 microliter buspirone or 8-OH-DPAT in the DR was also antagonized by 1 mg/kg p.o. 1-PP. The results suggest that buspirone possesses potential antidepressant properties but its effects may be masked in certain tests by its metabolite, 1PP, through its alpha 2 adrenergic blocking activity. PMID- 2905410 TI - Factors modifying the effect of diazepam on plasma corticosterone levels in rats. AB - We have examined factors that alter the effect of diazepam (DZ) on plasma corticosterone (CS) in rats. DZ had a biphasic effect on plasma CS levels: CS decreased with doses below 5 mg/kg and increased with higher doses. Peak response occurred 90 minutes post injection in both sexes. Plasma DZ levels were significantly higher in females than in males and peak at 10 and 30 minutes post injection in males and females, respectively. There was also a sex difference in the pattern of DZ metabolites. An acute stressor (30 minutes of immobilization) did not affect plasma CS levels in rats injected with a 5 mg/kg dose of DZ. Prenatally stressed animals did not differ in basal CS levels or in their response to 5 mg/kg of DZ compared to prenatally non-stressed animals. These two groups of animals also did not differ in plasma levels of DZ or of its metabolites. By contrast, the 5 mg/kg dose of DZ had no effect on plasma testosterone levels in control animals, but increased it in prenatally stressed animals. Furthermore, compared to non-stressed controls, prenatally stressed animals had lower baseline plasma testosterone levels. These results indicate that the effect of DZ on plasma CS is influenced by endogenous as well as exogenous factors and that these effects vary with the particular biochemical parameter under examination. PMID- 2905411 TI - Receptor regulation of ion transport in the intestinal epithelium. AB - The active transport of ions by the intestinal epithelium is regulated by a number of enteric neurotransmitters, hormones and other substances. Our knowledge of the receptors mediating the actions of these substances is generally fragmentary. This review summarizes current knowledge on the location and functional characteristics of transmitter receptors regulating transport function in the small intestine, highlighting recent research on cholinergic and bradykinin receptors. PMID- 2905412 TI - A possible role for MRI in polyarteritis nodosa: the "creeping fat" sign. AB - We describe a case of polyarteritis nodosa with diffuse abnormalities in subcutaneous fat by magnetic resonance imaging. These abnormalities returned to normal following treatment. Magnetic resonance imaging may have a role in the identification and diagnosis of systemic vasculitis. PMID- 2905413 TI - Possible tumour-initiating and -promoting activities of 3-diazo-N-nitrosobamethan in rat stomach mucosa. AB - 3-Diazo-N-nitrosobamethan (DNB), a mutagen produced by nitrite treatment of bamethan, a cardiovascular drug, induced unscheduled DNA synthesis in the pyloric mucosa of the stomach of male F344 rats 2 h after its administration by gastric tube at doses of 75 to 225 mg/kg body wt. DNB at a dose of 225 mg/kg body wt induced up to a 13-fold increase in replicative DNA synthesis with a maximum at 16 h after its administration. Moreover at doses of 75 to 225 mg/kg body wt, it induced up to a 12-fold increase in ornithine decarboxylase activity with a maximum after 16 h. The present results suggest that DNB has possible tumour initiating and -promoting activities in the pyloric mucosa of the rat stomach. However, the possible risks to patients posed by clinical use of bamethan cannot be evaluated until further work is completed. PMID- 2905414 TI - Seroepidemiologic study of adult T-cell leukemia virus (ATLV) and hepatitis B virus infection in Okinawa, Japan. AB - A total of 2,283 serum samples were collected from healthy subjects in three islands of the Yaeyama district of Okinawa, Japan. These sera were tested for the presence of hepatitis B surface antigen (HBsAg), for antibody to hepatitis B core antigen (anti-HBc), and for antibody to adult T-cell leukemia-associated antigen (anti-ATLA). Correlation between hepatitis B virus infection and adult T-cell leukemia virus (ATLV) infection was determined by using the prevalence rates for three virus markers. Overall prevalence of HBsAg, anti-HBc and anti-ATLA was 6.5%, 57.4%, and 17.9%, respectively. Age-specific prevalence of anti-HBc and anti-ATLA increased with age, but that of HBsAg did not. Sex-specific prevalence of HBsAg was significantly higher in males than in females, but that of anti-ATLA was significantly higher in females than in males. Statistical analysis revealed that prevalence of anti-ATLA was significantly higher in HBsAg-positive persons and HBsAg-negative/anti-HBc-positive persons than in those negative for HBsAg and anti-HBc. These data suggest that hepatitis B virus-infected persons have a significantly higher chance of adult T-cell leukemia virus infection than those without hepatitis B virus infection in the area studied. PMID- 2905415 TI - Suppressive effect of macrophages on interferon-gamma production by human peripheral lymphocytes stimulated with Mycoplasma pneumoniae. AB - Production of interferon (IFN)-gamma was investigated in human peripheral lymphocytes stimulated with Mycoplasma pneumoniae. Lymphocytes obtained from non immune individuals produced no IFN. IFN-gamma was produced by T cells obtained from immune individuals, and the helper/inducer T cells produced two- to sixfold higher titer of IFN-gamma than the suppressor/cytotoxic T cells. The addition of macrophages in T cell cultures suppressed the production of IFN-gamma; this differs from the previous result wherein the addition of macrophages enhanced the production of IFN-gamma, when stimulated with mumps virus or measles virus. PMID- 2905416 TI - [Effect of the activity of primary proton pumps on the growth of Escherichia coli in the presence of acetate]. AB - Escherichia coli batch cultures were grown under aerobic and anaerobic conditions on glucose with the substrate addition at pH 7.0. The cultures accumulated acetate in the medium at concentrations sufficient to inhibit the growth. This inhibitory effect of acetate was mediated apparently via its action on the intracellular pH. The inhibition of E. coli growth by acetate increased when the redox proton pump was switched off in the course of transition from aerobiosis to anaerobiosis and when the regulation of K+ fluxes was disordered in the presence of valinomycin. H+-ATPase was not essentially involved in maintaining the high rate of E. coli growth in the presence of acetate under aerobic conditions. If the activity of H+-ATPase was inhibited under anaerobic conditions at pH 7.0, the growth ceased after the dissipation of ionic gradients on the membrane. When CCCP was added under aerobic conditions, the growth did not stop at once if the medium had a pH of 7.6, but ceased immediately at pHout 7.0 in the glucose-salt medium. PMID- 2905417 TI - Pre-eclampsia: a hypothesis for its etiology. AB - A hypothesis is presented according to which the etiology of pregnancy-induced hypertension can be attributed to increased number of active uterine and arteriolar alpha-adrenergic myometrial receptors from pre-eclamptic patients in comparison with the alpha-adrenergic myometrial and arteriolar receptors from non pre-eclamptic patients. This condition could result in the increased uterine wall irritability and the decreased uteroplacental blood flow in pre-eclampsia. It is suggested that progesterone fails to induce a reduction in alpha 1-adrenergic receptors in the pre-eclamptic patient. This will require pre-eclamptic patients and matched controls to test the hypothesis. PMID- 2905418 TI - Pathogenesis of hepatic encephalopathy. PMID- 2905419 TI - Activities of neuronal and astrocytic marker enzymes in autopsied brain tissue from patients with hepatic encephalopathy. AB - Activities of the gamma-aminobutyric acid (GABA) and cholinergic nerve-terminal marker enzymes glutamic acid decarboxylase (GAD) and choline acetyltransferase (CAT) as well as the astrocytic enzyme glutamine synthetase (GS) were measured in homogenates of dissected brain tissue obtained at autopsy from nine cirrhotic patients dying in hepatic encephalopathy and an equal number of control subjects matched for age, agonal status, and time interval from death to freezing of autopsied material. GAD activities varied as a function of agonal status in control samples, confirming a previous report, but were unchanged in brain tissue from cirrhotic patients, suggesting no loss of integrity of presynaptic GABA nerve terminals in this disease. On the other hand, GS activities were selectively decreased by 25% (P less than 0.01) in caudate nuclei of cirrhotic patients, reflecting, no doubt, the severe astrocytosis consistently observed in this brain structure. CAT activities, expressed per milligram of protein, were found to be increased by 30% (P less than 0.01) in the prefrontal cortex of cirrhotic patients. Whether such changes result from a relative increase in CAT as a consequence of losses of astrocytic protein or reflect altered cholinergic function in hepatic encephalopathy associated with chronic liver disease awaits further study. PMID- 2905420 TI - DNA-binding activities of the Drosophila melanogaster even-skipped protein are mediated by its homeo domain and influenced by protein context. AB - The homeo box gene even-skipped (eve) encodes a 376-amino-acid protein that binds with high affinity to sequences located near the 5' termini of the eve and en genes. The 5' en sites are A + T rich and contain copies of the 10-base-pair (bp) consensus sequence T-C-A-A-T-T-A-A-A-T. In contrast, the 5' eve sites are G + C rich and contain the 9-bp sequence T-C-A-G-C-A-C-C-G. Among the five different homeo box proteins that have been tested for binding, eve is unique in that it shows virtually equal preference for the A + T-rich 5' en binding sites and the G + C-rich 5' eve sites. Most of the other proteins bind with a relatively higher affinity to the en sites than to the eve sites. In an effort to identify the regions of the eve protein that are responsible for its efficient binding to both classes of recognition sequences, we analyzed the DNA-binding properties of various mutant eve proteins. These studies suggest that the homeo domain of the eve protein is responsible for both binding activities. However, mutations in distant regions of the protein influenced the binding behavior of the eve homeo domain and caused a reduction in binding to the G + C class of recognition sites. We propose that the protein context of the homeo domain can influence its DNA binding properties. PMID- 2905421 TI - Extensive movement of LINES ONE sequences in beta-globin loci of Mus caroli and Mus domesticus. AB - LINES ONE (L1) is a family of movable DNA sequences found in mammals. To measure the rate of their movement, we have compared the positions of L1 elements within homologous genetic loci that are separated by known divergence times. Two models that predict different outcomes of this analysis have been proposed for the behavior of L1 sequences. (i) Previous theoretical studies of concerted evolution in L1 have indicated that the majority of the 100,000 extant L1 elements may have inserted as recently as within the last 3 million years. (ii) Gene conversion has been proposed as an alternative to a history of prolific recent insertions. To distinguish between these two models, we cloned and characterized two embryonic beta-globin haplotypes from Mus caroli and compared them with those of M. domesticus. In 9 of 10 instances, we observed an L1 element to be present in one chromosome and absent at the same site in a homologous chromosome. This frequency is quantitatively consistent with the known rate of concerted evolution. Therefore, we conclude that gene conversion is not required for concerted evolution of the L1 family in the mouse. Furthermore, we show that the extensive movement of L1 sequences contributes to restriction fragment length polymorphism. L1 insertions may be the predominant cause of restriction fragment length polymorphisms in closely related haplotypes. PMID- 2905422 TI - Positional and developmental regulation of glutamine synthetase expression in mouse liver. AB - In situ hybridization showed that all fetal hepatocytes contain glutamine synthetase (GS) mRNA but that in adult mouse liver, only a single cell layer surrounding the central veins contains GS mRNA. A shift from the fetal to the adult pattern begins within a few days of birth and is complete within 12 days of birth. Since the total GS mRNA and the transcription rate of the single GS gene are similar at birth and in adults, we conclude that there is a generalized reduction in GS transcription for most hepatocytes and a sharp rise in GS transcription for the immediate pericentral cells. This may be a case of positional regulation of specific gene transcription in apparently a single cell lineage. PMID- 2905423 TI - A dominant trifluoperazine resistance gene from Saccharomyces cerevisiae has homology with F0F1 ATP synthase and confers calcium-sensitive growth. AB - The antipsychotic drug trifluoperazine has been long considered a calmodulin inhibitor from in vitro studies but may function in vivo as a more general inhibitor by disturbing ion fluxes and altering the membrane potential. Resistance to trifluoperazine can arise in Saccharomyces cerevisiae cells by alterations in at least three distinct genetic loci. One locus, defined by a spontaneous dominant trifluoperazine resistance mutation (TFP1-408), was isolated and sequenced. The sequence of the TFP1-408 gene revealed a large open reading frame coding for a large protein of 1,031 amino acids with predicted hydrophobic transmembrane domains. A search of existing amino acid sequences revealed a significant homology with F0F1 ATP synthase. Mutant TFP1-408 cells did not grow efficiently in the presence of 50 mM CaCl2, whereas wild-type cells did. Wild type cells became resistant to trifluoperazine in the presence of 50 mM CaCl2 or 50 mM MgCl2. Mutant cells showed a higher rate of calcium transport relative to wild-type cells. These data suggest that the TFP1 gene product codes for a transmembrane ATPase-like enzyme possibly involved in Ca2+ transport or in generating a transmembrane ion gradient between two cellular compartments. PMID- 2905424 TI - Genetic analysis of small nuclear RNAs in Saccharomyces cerevisiae: viable sextuple mutant. AB - Saccharomyces cerevisiae contains at least 24 distinct small nuclear RNAs (snRNAs), several of which are known to be essential for viability and to participate in the splicing of pre-mRNAs; the RNAs in this subset contain binding sites for the Sm antigen, a hallmark of metazoan snRNAs involved in mRNA processing. In contrast, we showed previously that the single-copy genes for three other snRNAs (snR3, snR4, and snR10) are not required for viability, although cells lacking snR10 are growth impaired at low temperature. None of these RNAs associates with the Sm antigen. To assess this apparent correlation, we cloned and sequenced the genes encoding three additional non-Sm snRNAs. Comparison of these genes with nine additional yeast snRNA genes revealed a highly conserved TATA box located 92 +/- 8 nucleotides 5' of the transcriptional start site. By using the technique of gene replacement with null alleles, each of these three single copy genes was shown to be completely dispensable. We constructed multiple mutants to test the hypothesis that, individually, each of these snRNAs is nonessential because the snRNAs play functionally overlapping roles. A mutant lacking five snRNAs (snR3, snR4, snR5, snR8, snR9) was indistinguishable from the wild type, and growth of the sextuple mutant was no more impaired than that in strains lacking only snR10. This widespread dispensability of snRNAs was completely unexpected and forces us to reconsider the possible roles of these ubiquitous RNAs. PMID- 2905425 TI - TATA box-dependent protein-DNA interactions are detected on heat shock and histone gene promoters in nuclear extracts derived from Drosophila melanogaster embryos. AB - We monitored protein-DNA interactions that occur on the hsp26, hsp70, histone H3, and histone H4 promoters in nuclear extracts derived from frozen Drosophila melanogaster embryos. All four of these promoters were found to be transcribed in vitro at comparable levels by extracts from both heat-shocked and non-heat shocked embryos. Factors were detected in both types of extracts that block exonuclease digestion from a downstream site at ca. +35 and -20 base pairs from the start of transcription of all four of these promoters. In addition, factors in extracts from heat-shocked embryos blocked exonuclease digestion at sites flanking the heat shock consensus sequences of hsp26 and hsp70. Competition experiments indicated that common factors cause the +35 and -20 barriers on all four promoters in both extracts. The formation of the barriers at +35 and -20 required a TATA box but did not appear to require specific sequences downstream of +7. We suggest that the factors responsible for the +35 and -20 barriers are components whose association with the promoter precedes transcriptional activation. PMID- 2905426 TI - Identification and characterization of multiple erythroid cell proteins that interact with the promoter of the murine alpha-globin gene. AB - The proteins responsible for erythroid-specific footprints extending to -180 on the mouse alpha-globin gene were identified, enriched, and characterized from extracts of murine erythroleukemia (MEL) cells. Three proteins accounted for most aspects of the footprints. The binding sites of two proteins, termed alpha-CP1 and alpha-CP2, overlapped in the CCAAT box. Further characterization of these two CCAAT binding proteins showed that neither interacted with the adenovirus origin of replication, a strong CCAAT transcription factor-nuclear factor 1 binding site. A third protein, termed alpha-IRP, interacted with two sequences that formed an inverted repeat (IR) between the CCAAT and TATAA boxes. Interestingly, the binding domain of one of the CCAAT factors, alpha-CP1, overlapped one alpha IRP binding site. alpha-CP1 thus overlapped the binding domains of both alpha-CP2 and alpha-IRP. The IRs included GC-rich sequences reminiscent of SP1-binding sites. Indeed, alpha-IRP bound as well to the alpha-promoter as it did to SP1 sites in the simian virus 40 early promoter. These results suggest that alpha-IRP may be related to the transcription factor Sp1. We determined the level of each alpha-globin-binding activity before and after induced erythroid differentiation of MEL cells. We found that differentiation caused alpha-CP1 activity to drop three- to fivefold, while alpha-IRP activity decreased slightly and alpha-CP2 activity increased two- to threefold. PMID- 2905428 TI - Intracranial cocaine self-administration. PMID- 2905427 TI - Neurochemical findings in neuroacanthocytosis. AB - We performed a neurochemical study of the brain of two unrelated patients, living in different continents, with neuroacanthocytosis. The levels of monoamines and their metabolites, gamma-aminobutyric acid and substance P, were measured in several brain areas and the monoamine metabolites in cerebrospinal fluid. The binding of 3H-spiperone to striatal membranes and to lymphocytes was also measured. Both patients had a progressive neurological disorder with onset in the third decade of life and characterized by a complex movement disorder, epilepsy, muscular wasting, and changes in behavior. The movement disorder initially manifested with oromandibular dystonia and limb chorea, but at the time of death was characterized by a severe dystonic syndrome. The chemical changes were similar in the two patients. The most important neurochemical findings were a depletion of dopamine and its metabolites in most brain areas, most notably in the striatum, and elevation of norepinephrine levels in the putamen and globus pallidus. Substance P was markedly reduced in the striatum and substantia nigra. Our findings may provide clues to the neurochemical mechanisms underlying dystonia. PMID- 2905429 TI - Psychomotor stimulant vs. local anesthetic effects of cocaine: role of behavioral sensitization and kindling. PMID- 2905430 TI - Specific neurochemical systems and memory. AB - This commentary addresses issues raised in common by the various authors of papers in this section: the role of different chemical systems in memory, new approaches for assessing the effects of drugs, and issues for the future in evaluating animal models of human disorders of memory. PMID- 2905431 TI - Amnesia and Alzheimer's disease: which neurotransmitter system is responsible? AB - The cholinergic, noradrenergic, and serotonergic neurotransmitter systems show a consistent pattern of degeneration associated with Alzheimer's disease (AD) and, to a lesser extent, normal aging. The review articles in this section draw a relation between degeneration of one or more of these systems and impairments in learning and memory. Cholinergic hypofunction may underlie the amnesia associated with AD but not that associated with normal aging. The relevance of impaired serotonergic or noradrenergic function to any cognitive impairment associated with aging or AD remains undetermined. PMID- 2905432 TI - Specific and nonspecific components of the neurohumoral link of food refusal conditioned response in the snail. PMID- 2905433 TI - [Coronary disease of the aneurysmal type in a young patient: a possible expression of panarteritis nodosa]. PMID- 2905434 TI - [A case of giant hepatic hydatid cyst]. PMID- 2905435 TI - [Alcohol withdrawal syndrome. Effects of short-term treatment with dapiprazole]. AB - A study on dapiprazole, a new psychotropic agent, in the treatment of patients during the alcohol withdrawal syndrome, is reported. On the basis of evaluations made on the severity of the physical and psychic symptoms of withdrawal, the conclusion is drawn that the new psychotropic agent, administered at gradually increasing doses of 40 to 90 mg/kg for 7 days, completely controls the clinical symptomatology at least in 70% of the cases treated. PMID- 2905436 TI - Immunohistochemical demonstration of tyrosine hydroxylase (TH)-positive but dopamine beta-hydroxylase (DBH)-negative neuron-like cells in the pineal gland of golden hamsters. AB - Double immunostaining for tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) in the pineal gland revealed many TH-positive but DBH-negative, neuron-like cells in golden hamsters, but not in rats and gerbils. They were scattered in the meshwork of TH- and DBH-positive nerve fibers throughout the parenchyma. Their cell bodies were oval or spindle-shaped (maximum diameter: 15-20 micron). They had sometimes one or two short cell processes. Bilateral superior cervical ganglionectomy diminished strikingly the number of TH- and DBH-positive nerve fibers, but did not affect the number of TH-positive cells. PMID- 2905437 TI - Direct demonstration of an N-methyl-D-aspartate receptor mediated component of excitatory synaptic transmission in area CA1 of the rat hippocampus. AB - The action of a new non-N-methyl-D-aspartate (NMDA) receptor antagonist, 6-cyano 7-nitroquinoxaline-2,3-dione (CNQX), on synaptic transmission in area CA1 of the rat hippocampus has been examined. Intracellular and extracellular recordings showed CNQX to be a potent antagonist of synaptic potentials evoked by stimulation of the Schaffer collateral-commissural fibre system. One to 2 microM CNQX was sufficient to reduce the excitatory postsynaptic potential (EPSP) by 50%. CNQX is therefore about 100 times more potent than previously available non NMDA receptor antagonists. In the presence of CNQX, a small depolarizing potential could still be evoked. This potential was sensitive to the NMDA receptor blocker, 2-amino-5-phosphonovaleric acid (APV), increased in size on depolarizing the neurone and also increased in size on removing Mg2+ from the perfusing medium. This residual EPSP therefore has characteristics which are consistent with its mediation via the NMDA receptor-coupled ionophore. These results indicate a dual composition of the monosynaptic excitatory potential in area CA1. PMID- 2905438 TI - Inhibition of spinal nociceptive neurons by excitation of cell bodies or fibers of passage at various brainstem sites in the cat. AB - The relative contribution of cells of origin and fibers of passage to the inhibition of spinal nociceptive neurons from various brainstem sites is not known. The present study therefore quantitatively compares the descending inhibition produced by focal electrical stimulation which indiscriminatively excites all neuronal elements with the inhibition evoked by glutamate microinjections which selectively excite cell bodies at the same sites within the midbrain periaqueductal gray (PAG) and neighboring lateral reticular formation (LRF) and within the medullary nucleus raphe magnus (NRM). In pentobarbital anesthetized cats extracellular recordings were made from 22 lumbar dorsal horn neurons responding to innocuous mechanical skin stimuli and to noxious radiant heating of the glabrous skin at the ipsilateral hindpaw. Glutamate microinjections (1 microliter, 0.5 M) into 6 of 10 sites within the NRM reduced heat-evoked responses in 6 different cats to 69.2 +/- 3.8% of control. Electrical stimulation (180-600 microA) at the same sites and two additional sites in the NRM reduced responses to 50.0 +/- 8.7% of control. At 4 of 10 sites within the PAG glutamate reduced spinal neuronal responses to heat in 4 different cats to 69.4 +/- 6.1% of control. Electrical stimulation at 3 of the same sites and 6 additional sites within the PAG reduced heat-evoked responses to 52.7 +/- 3.5% of control. Microinjections of glutamate into the LRF failed to affect heat-evoked responses in any of the 8 experiments tested, while electrical stimulation at 6 of the same sites in the LRF reduced neuronal responses to heat to 52.4 +/- 7.1% of control.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2905439 TI - The development of encapsulated filtering blebs. AB - The development of an encapsulated filtering bleb (Tenon's cyst) complicated 56 of 409 consecutive filtering operations (13.7%) performed during a 40-month period after January 1983. Fifteen eyes (27.8% of encapsulated blebs) required surgical revision. The recognition of bleb encapsulation occurred 20.4 +/- 12.7 days (mean +/- standard deviation) postoperatively. Prolonged duration of beta adrenergic antagonist therapy was associated with an increased frequency of bleb encapsulation (180.6 +/- 128.5 weeks without encapsulation, 229.0 +/- 129.3 weeks with encapsulation, P less than 0.009). Bleb encapsulation occurred in 42 of 272 eyes with previous argon laser trabeculoplasty, but in only 4 of 85 eyes without any previous anterior segment laser (P less than 0.01). Encapsulated filtering blebs developed in 4 of 12 (33.3%) eyes with congenital glaucoma and 4 of 9 (44.4%) eyes with juvenile glaucoma (P less than 0.0002). The intraocular pressures (IOPs) in the eyes with encapsulated filtering blebs were significantly elevated at 1, 2, and 3 postoperative weeks, and at final follow-up compared with eyes without bleb encapsulation. PMID- 2905440 TI - [Closed dislocation of the 1st cuneiform bone of the foot]. PMID- 2905441 TI - [The neuroendocrinology of puberty]. PMID- 2905442 TI - Identification of the binding sites for potential regulatory proteins in the upstream enhancer element of the Drosophila fushi tarazu gene. AB - With a view to identifying proteins that regulate the expression of the Drosophila ftz gene we have sequenced its enhancer-like upstream element (USE) and determined the binding sites for embryonic nuclear proteins within this region by in vitro DNAaseI footprinting. We find that greater than 50% of this element is bound by nuclear protein. By footprinting and gel-retardation studies in embryonic extracts from different developmental stages, we have characterised a number of USE/protein complexes whose nature alters in concert with changes in the ftz expression pattern, suggesting that these USE-binding proteins may be involved in the regulation of gene activity. In some cases this suggestion is substantiated by the observation that the protected DNA sequences show homology to the binding sites for ftz regulating DNA-binding proteins such as the pair rule gene product even-skipped. PMID- 2905444 TI - Mapping of D4S98/S114/S113 confines the Huntington's defect to a reduced physical region at the telomere of chromosome 4. AB - The dominant gene defect in Huntington's disease (HD) is linked to the DNA marker D4S10, near the telomere of the chromosome 4 short arm. Two other markers, D4S43 and D4S95, are closer, but still proximal to the HD gene in 4p16.3. We have characterized a new locus, D4S114, identified by cloning the end of a NotI fragment resolved by pulsed-field gel electrophoresis. D4S114 was localized distal to D4S43 and D4S95 by both physical and genetic mapping techniques. The "end"-clone overlaps a previously isolated NotI "linking" clone, and is within 150 kb of a second "linking" clone defining D4S113. Restriction fragment length polymorphisms for D4S113 and D4S114, one of which is identical to a SacI polymorphism detected by the anonymous probe pBS731B-C (D4S98), were typed for key crossovers in HD and reference pedigrees. The data support the locus order D4S10-(D4S43, D4S95)-D4S98/S114/S113-HD-telomere. The D4S98/S114/S113 cluster therefore represents the nearest cloned sequences to HD, and provides a valuable new point for launching directional cloning strategies to isolate and characterize this disease gene. PMID- 2905443 TI - Stage- and tissue-specific expression of two homeo box genes in sea urchin embryos and adults. AB - We report the isolation of two different homeo box genes, HB3 and HB4, from the Hawaiian sea urchin Tripneustes gratilla. DNA sequencing revealed a definitive Antennapedia (Antp) class homeo box in each gene. Southern transfer hybridizations showed the genes to be single-copy. A 5.7-kb transcript of the HB3 gene was found in ovary, testis, small intestine and gastrula poly(A)+ RNA. The HB4 gene produces three transcripts. A 3.7-kb and a 4.4-kb transcript are expressed during embryogenesis. A 3.5-kb transcript appears in each of the adult tissues studied. The HB4 gene appears to be the sea urchin cognate of the Drosophila infrabdominal-7 (iab-7) gene, the mouse Hox 1.7 and Hox 3.2 genes and the Xenopus X1Hbox 6 gene. An examination of Antp class homeo box genes in deuterostomes indicates that a chromosomal duplication has taken place in the evolutionary line leading to the vertebrates after the divergence of the echinoderms. Thus, the sea urchin represents the primitive condition. PMID- 2905445 TI - Gamma-glutamyl transferase locus (GGT) displays a PvuII polymorphism. PMID- 2905446 TI - Two RFLPS approximately 7 kb 5' of the human protein C gene. PMID- 2905447 TI - A polymorphic HindIII site within the human multidrug resistance gene 1 (MDR1). PMID- 2905448 TI - A new TaqI polymorphism of the complement factor B gene. PMID- 2905449 TI - An Eco RI restriction length polymorphism at the murine L-myc locus. PMID- 2905450 TI - A HindIII polymorphism identified by the human early growth response gene 2 (EGR2) on chromosome 10. PMID- 2905451 TI - Bst-1 RFLP at the human lipoprotein lipase (LPL) gene locus. PMID- 2905452 TI - A Pvu II RFLP in the human ADH3 gene. PMID- 2905453 TI - Psychopharmacology and the management of violent patients. AB - Human aggression is a complex behavior with multiple determinants for which there are as yet no specific drug treatments. This article reviews case reports and clinical studies of the use of various classes of medication in aggressive individuals. In addition, pharmacologic approaches to the acutely agitated patient are described. Recent studies of the beta-blockers and carbamazepine suggest that these agents may be of benefit in certain aggressive individuals. Methodologic limitations of extant clinical studies of the pharmacologic management of the violent patient are described as well. PMID- 2905454 TI - First trimester prenatal diagnosis of haemophilia A: two years' experience. AB - We evaluated the feasibility, reliability, and acceptability of prenatal diagnosis of haemophilia A by DNA analysis of chorionic villi. Twenty-two women at risk to transmit the abnormal gene were referred for prenatal diagnosis, two of them twice. Two of the 22 women appeared to be non-carriers by DNA analysis. In one of these women, the results were known only after chorionic villus sampling had been carried out. Thirteen of the twenty carriers were heterozygous for an intragenic (Bc1I or XbaI) marker; six women were only heterozygous for the extragenic DXS52 (St14) locus. One of the women was homozygous for all the presently known DNA markers within or closely linked with the factor VIII locus. Twelve of the 22 fetuses at risk were male, ten were female. Seven of the 12 male fetuses were shown to be affected and were subsequently aborted. Four male fetuses appeared to be not affected. In one case, the diagnosis was made by use of an extragenic marker. The woman rejected fetal blood sampling to confirm the diagnosis. After birth, a normal factor VIII level was found in three of the four cases. The fourth pregnancy is still continuing. In one of the 12 male fetuses, no diagnosis at the gene level was possible. DNA analysis is expected to provide maximum certainty as to the phenotype of the fetus for approximately 60 per cent of the women; for another 37 per cent a rate of misdiagnosis of 4-5 per cent applies. In only 3 per cent of the cases will no diagnosis at the gene level be possible as yet. The new possibility of a prenatal diagnosis in the first trimester of pregnancy enabled some of these women to have a family of their own and was appreciated in particular by the women who underwent fetoscopy in an earlier pregnancy. PMID- 2905455 TI - [Clinical evaluation of drug interactions of cyclosporin]. AB - Cyclosporin is a nephrotoxic immunosuppressant metabolized in the liver and requiring drug monitoring. Numerous pharmacokinetic and pharmacodynamic drug interactions have occurred with this compound. Some of them are well substantiated while others are merely suspected. The major interactions must definitely be prevented of corrected, whereas the others need no more than careful drug monitoring. PMID- 2905456 TI - [Exercise-induced asthma]. AB - Exercise-induced asthma only differs from common asthma in its causative factor. It is a typical asthmatic attack which follows a strenuous and continuous physical exercise lasting 5 to 10 minutes, most often in cold and dry weather. The prevalence of exercise-induced asthma has not yet been firmly established; its pathophysiological mechanisms are still debated, and the respective roles of heat and water losses by the airways are not clearly defined. However, the influence of the type of exercise as a precipitating factor of exercise-induced asthma is now well-known. All things being equal, swimming generates less asthma than running and cycling. This enables the subjects to be directed towards the most suitable sports and encouraged to improve their physical fitness. Drug treatment of exercise-induced asthma must preferentially be preventive; it relies on cromoglycate and beta-2 adrenergic agonists, the latter being also capable of treating acute exercise-induced bronchial obstruction. Education of the patients and their family is also important. PMID- 2905457 TI - Protein phosphorylation and hormone action. AB - Many key regulatory proteins exist in cells as either a phosphorylated or a dephosphorylated form, their steady-state levels of phosphorylation reflecting the relative activities of the protein kinases and protein phosphatases that catalyse the interconversion process. Phosphorylation of seryl or threonyl (and occasionally tyrosyl) residues triggers small conformational changes in these proteins that alter their biological properties. Hormones and other extracellular signals transmit information to the interior of the cell by activating transmembrane signalling systems that control the production of a relatively small number of chemical mediators, termed 'second messengers'. These substances regulate the activities of protein kinases and phosphatases, and so alter the phosphorylation states of many intracellular proteins, accounting for the diversity of action of hormones. In this lecture I review recent work which demonstrates that a wide variety of cellular processes are controlled by relatively few protein kinases and protein phosphatases with pleiotropic actions. These enzymes provide the basis of an interlocking network that allows extracellular signals to coordinate biochemical functions. PMID- 2905458 TI - Response characteristics of neurons in chick forebrain slices. AB - Coronal sections were taken from the forebrains of domestic chicks, aged 1-20 days, and maintained in vitro. Extracellular recordings of neural activity were made from the intermediate part of the medial hyperstriatum ventrale (IMHV). Spontaneous activity was rarely recorded, but neuronal responses could be evoked by stimulation of various sites. Each recording point was surrounded by an arc of sites which, when stimulated, typically elicited a short-latency field potential. These 'local responses' could be recorded in slices from chicks of any age. Stimulation of more distant sites failed to evoke field potentials from the IMHV. Instead, trains of large, unit action potentials appeared on an undisturbed baseline. Such 'unit' responses could only be evoked by stimuli delivered at specific frequencies. They required facilitation, were of variable latency, and often finally decayed. The number of sites capable of evoking a 'unit' response from the IMHV fell dramatically in slices taken from chicks older than 4 days. PMID- 2905459 TI - Expression of GABA and glycine receptors by messenger RNAs from the developing rat cerebral cortex. AB - The ontogenesis of mRNAs coding for GABA and glycine receptors in the cerebral cortex of the rat was examined by extracting poly(A)+ mRNA from the brains of embryonic, postnatal or adult rats and injecting it into Xenopus oocytes. The ability of a messenger to express functional receptors was then assayed by measuring the membrane currents elicited by the agonists. The size of the GABA induced current increased progressively with age, being undetectable in oocytes injected with mRNA from embryonic day 15 and reaching a maximum in oocytes injected with mRNA from postnatal day 30. In contrast, the glycine-induced response was negligible in oocytes injected with mRNA from the cerebral hemispheres of embryos 15 days old; it increased sharply to a maximum with newborn animals and then decreased with age to become very small with mRNA from adult cortex. GABA and glycine receptors induced by mRNA from the cerebral cortex of all ages are associated with chloride channels. PMID- 2905460 TI - The effect of photoreceptor coupling and synapse nonlinearity on signal:noise ratio in early visual processing. AB - Electrical coupling of vertebrate photoreceptors is well known to improve the signal: noise ratio in the photoreceptor layer for large-area stimuli. For example, if N photoreceptors are perfectly coupled to each other, the signal: noise ratio is improved for stimuli illuminating more than a number M = square root of N of the receptors but is made worse for small-area stimuli illuminating less than M of the N receptors. Using the model of Lamb & Simon (J. Physiol., Lond. 263, 257 (1976], which treats the photoreceptor layer as a square array of cells, each coupled through a resistive gap junction to the four cells around it, we show that the signal:noise ratio for small-area stimuli is much greater than would be expected from a model in which receptors are assumed to be perfectly coupled. Contrary to predictions made assuming perfect coupling, receptor coupling should not prevent rods from detecting single photons, but whether the single photon signal can be detected at the bipolar cell level depends on how signals are read out of the receptor layer. The signal:noise ratio in bipolar cells postsynaptic to the photo-receptor layer is determined partly by synaptic convergence and nonlinearity in synaptic transmission from receptors. If the synaptic gain decreases with light-induced receptor hyperpolarization, as is found experimentally, then receptor coupling can improve the postsynaptic signal:noise ratio for stimuli illuminating only one receptor, even though coupling decreases the presynaptic signal:noise ratio for such stimuli. Moreover, increasing the number of coupled receptors projecting to a bipolar cell can improve the signal:noise ratio for localized stimuli if the synapse is sufficiently nonlinear (although, for the degree of nonlinearity seen in lower vertebrates, synaptic convergence makes the ratio worse for the single photon event). The fact that receptor coupling and synaptic convergence can, under some circumstances, improve the signal:noise ratio in bipolar cells suggests a principle of retinal design that may compete with the requirements of high spatial resolution. PMID- 2905461 TI - Development of ionic conductances in neurons of the inferior olive in the rat: an in vitro study. AB - Neurons of the inferior olive of the rat were studied at different stages of their postnatal (PN) development by using the current clamp technique in slices maintained in vitro. Antidromic and synaptic activation of inferior olivary neurons could be achieved in preparations as young as PN day 2. Neurons at this age already exhibited a variety of ionic conductances which included fast sodium dependent spikes, high-threshold and low-threshold calcium spikes, potassium dependent currents, Ca-dependent after-hyperpolarizing potentials (AHPS), and both instantaneous and time-dependent inward rectification at hyperpolarized levels of membrane potential. The two types of Ca-dependent responses recorded in olivary neurons during the first postnatal week were graded with the magnitude of the depolarization imposed on the cells. Furthermore, the high-threshold Ca spikes were only clearly observed during this early period when K conductances were depressed by the injection of caesium into the cells or by bath application of 4-aminopyridine. In contrast, the high-threshold Ca spikes could be obtained without suppression of K currents and were all-or-none in character in some neurons after PN day 8 and in all neurons after PN day 11. The observations suggest that the balance between K and Ca currents changes throughout maturation and is largely in favour of the K current until about the end of the first PN week. At all ages studied, the low-threshold Ca spikes were much less sensitive to the Ca channel blocker cadmium than were the high-threshold Ca spikes. Finally, spontaneous, regular oscillations of the membrane potential were observed for the first time at PN day 16 and were only commonly observed after PN day 19, suggesting a late development of electrotonic coupling between olivary neurons. PMID- 2905462 TI - The effect of Escherichia coli STa enterotoxin and other secretagogues on mucosal surface pH of rat small intestine in vivo. AB - The mucosal surface pH of rat small intestine was measured in vivo. The surface pH in the normal jejunum was 6.20 +/- 0.02 (67) and 7.00 +/- 0.05 (5) in the ileum. Escherichia coli STa toxin induced a rapid and reversible alkalinization of both jejunal and ileal mucosae to a pH of 6.91 +/- 0.08 (10) and 7.67 +/- 0.06 (5) respectively. The synthetic ST analogue, STh-(6-19), had an effect identical to native STa toxin on jejunal surface pH. Theophylline (20 mM) maintained the STa-elevated jejunal surface pH after toxin removal but had no effect on untreated tissue. 8-Bromo cyclic GMP resembled STa by causing similar mucosal alkalinization in the jejunum; 8-bromo cyclic AMP, forskolin and cholera toxin individually had considerably smaller effects on surface pH, although combining forskolin or cholera toxin with theophylline resulted in alkalinization of the jejunal mucosa to a pH of 6.92 +/- 0.03 (5) and 6.76 +/- 0.04 (4). These results indicate that cyclic-GMP-dependent secretory processes are more capable of inducing surface pH changes than those dependent on cyclic AMP. The ability of STa to alter mucosal surface pH makes it a useful tool to investigate the microclimate hypothesis for weak electrolyte absorption. PMID- 2905463 TI - The influence of dietary protein on the experimental epidemiology of Heligmosomoides polygyrus (Nematoda) in the laboratory mouse. AB - The influence of dietary protein on the epidemiology of an intestinal helminth infection was investigated with an experimental system that allowed transmission of the nematode Heligmosomoides polygyrus to occur naturally between laboratory mice. Mortality of mice was greatly increased in infected populations that were fed ad libitum on synthetic diets containing 2% compared with 16% protein. Larger numbers of larval and adult H. polygyrus were found to infect mice in the low protein cage compared with the high-protein cage. No evidence for density dependence in the fecundity of female worms was detected; on average the daily egg output per female worm was greater for parasites infecting mice in the low protein cage. The rate at which naive mice acquired infection was also higher in the low-protein cage. Pinworm (Aspiculuris tetraptera) became established in each cage, and average worm burdens were again greater in the low-protein cage. The acquisition of resistance to reinfection was not found to be an important factor influencing the survival of parasites infecting mice in either cage. The epidemiology of H. polygyrus and A. tetraptera was therefore characterized by low average worm burdens and high host survival in a well-nourished population of mice, and by a high intensity of infection and severe parasite-induced host mortality in a malnourished colony of mice. This reflects differences in the survival and fecundity of adult parasites between mice in the two cages, and suggests that malnourished mice are predisposed to acquire large numbers of several species of intestinal worm. PMID- 2905464 TI - Identification of beta adrenoceptor subtype in human coronary artery. PMID- 2905465 TI - Is 2-bromo-D-lysergic acid diethylamide (BOL) an allosteric antagonist of serotonergic receptors in rabbit atria? PMID- 2905466 TI - High affinity neurotransmitter and drug receptors in human lung preparations. PMID- 2905467 TI - Highly selective mu opioid antagonist peptides block spinal mu opioid inhibition of gastrointestinal transit. PMID- 2905468 TI - Synergistic renal effects of RS-10085, an ace inhibitor, and fenoldopam, a DA1 agonist, in the rat. PMID- 2905469 TI - Effects of clozapine on fixed-consecutive-number responding in rats: a comparison to other neuroleptic drugs. AB - The effects of clozapine and several other neuroleptic drugs were examined in rats responding under fixed-consecutive-number (FCN) schedules with minimum response requirements of 4 and 8. Under these schedules, rats were trained to respond either 8 or more times or 4 or more times on one lever, and then respond once on a second lever. In one component of these schedules, an external discriminative stimulus was presented following the completion of the response requirement on the first lever, whereas no stimulus change was programmed under the other. Under the FCN 8 schedule without the external discriminative stimulus, clozapine produced large dose-dependent decreases in accuracy (percent of reinforced response runs), whereas molindone produced small decreases in accuracy. Neither clozapine or molindone, however, altered accuracy under the FCN 4 without the external discriminative stimulus. Under these same schedules, loxapine, chlorpromazine, haloperidol and thioridazine produced small increases in accuracy at intermediate doses without affecting accuracy at the low and high doses. None of the neuroleptics evaluated produced accuracy-altering effects under the FCN schedules with the external discriminative stimulus. In general, all of these drugs decreased response rates in a dose-dependent fashion. The order of potency for the rate-decreasing effects of these drugs was loxapine greater than haloperidol greater than molindone greater than clozapine = chlorpromazine greater than thioridazine. Thus, the effects of clozapine on accuracy under the FCN schedules without the external discriminative stimulus differed qualitatively from those of other neuroleptic agents. PMID- 2905470 TI - Effects of buspirone differ from those of gepirone and 8-hydroxy-2-(di-n propylamino)tetralin (8-OH-DPAT) on unpunished responding of pigeons. AB - Under several behavioral procedures, such as punished responding and drug discrimination, the effects of the atypical anxiolytic buspirone are similar to those of its analogue gepirone, and to those of the 5-HT1A receptor agonist 8-OH DPAT. Similarities in the effects of these compounds occur despite the fact that buspirone produces strong dopaminergic actions, whereas both gepirone and 8-OH DPAT effects mainly appear to be serotonergically mediated. When keypeck responding of pigeons was maintained under a multiple 3-min fixed-interval, 30 response fixed ratio schedule of food presentation, responding under both the fixed-interval and fixed-ratio schedules was decreased over a range of buspirone doses (0.3-5.6 mg/kg). As has been reported with many antipsychotic compounds, performance under the fixed-interval schedule was more sensitive to the rate decreasing effects of buspirone. In contrast, both gepirone (0.03-3.0 mg/kg) and 8-OH-DPAT (0.03-1.0 mg/kg) increased responding under the two schedules. Differences in the effects of buspirone from the other compounds in this study, compared to the similar effects of these drugs obtained using other procedures, emphasize the importance of the specific behavior as a determinant of drug action. The multiple fixed-interval, fixed-ratio schedule may be useful for delineating the relative balance of dopaminergic and serotonergic effects produced by drugs that are less apparent using other behavioral procedures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2905471 TI - The role of central- and peripheral-type benzodiazepine receptors in anxiolytic agent augmentation of NaCl solution intake: effects of clonazepam and Ro 5-4864. AB - Two 1,4 benzodiazepines bind preferentially to the central- and peripheral-type benzodiazepine receptor in the brain, clonazepam and Ro 5-4864, respectively. They were administered to rats to determine if the relation between known anxiolytic action and efficacy in augmenting NaCl solution ingestion in rehydrating rats would remain the case for these prototypic agents. Clonazepam (0.062-32.0 mg/kg, PO) was highly potent and efficacious and increased 1.5% NaCl solution intake in a dose-related fashion. Water intake could also be increased, but to a relatively minor degree. Ro 5-4864 (4-8 mg/kg, IP) did not affect 1.5% NaCl solution ingestion, nor did this dose range suppress the augmenting effect of clonazepam (0.5-2.0 mg/kg, PO) on the solution intake. Since clonazepam does, and Ro 5-4864 does not, possess punishment-attenuation properties in other tests, drug augmentation of NaCl solution ingestion by rehydrating rats continues to correlate well with known anxiolytic action. PMID- 2905472 TI - Conditioned defensive burying as a model for identifying anxiolytics. AB - Rats exposed to a presumably aversive stimulus such as electric shock respond by heaping litter on the source, a behavior known as conditioned defensive burying (CDB). Because some anxiolytics suppress this behavior, CDB has been proposed as a screening method for anxiolytics. We tested the effects of the conventional anxiolytics chlordiazepoxide (4-32 mg/kg) and meprobamate (75-125 mg/kg), the novel anxiolytic buspirone (8-64 mg/kg), the antidepressant imipramine (4-16 mg/kg), the opiate analgesic morphine (2-8 mg/kg), and the antipsychotic chlorpromazine (1-16 mg/kg) on CDB. Chlordiazepoxide, meprobamate, imipramine, and morphine significantly suppressed CDB, but chlordiazepoxide did so only at a dose that reduced general activity. Buspirone and chlorpromazine did not suppress CDB at doses that reduced activity. There were some methodological differences from previous studies. We conclude that the test as constituted in this study lacks drug-class specificity. The necessity of distinguishing between specific reduction of burying and general reduction of activity is emphasized. PMID- 2905473 TI - H2-receptor-mediated stress-induced analgesia is dependent on neither pituitary nor adrenal activation. AB - The effects of hypophysectomy and adrenalectomy were studied on the analgesia elicited by a 3 min exposure to 3.5 mA of continuous inescapable footshock, a response previously shown to be resistant to high doses of the opiate antagonist, naloxone, but inhibited by antagonists of histamine H2-receptors. Neither treatment significantly attenuated the response, and the brain-penetrating H2 receptor antagonist zolantidine inhibited the response in all surgical treatment groups. These results add further support for our hypothesis that brain histamine and brain H2-receptors mediate nonopiate analgesia. PMID- 2905474 TI - Neuro-endocrine changes as new targets in the drug treatment of congestive heart failure. AB - The classical therapy of congestive heart failure (CHF) with inotropic agents (digitalis and newer inotropics) and diuretic agents remains unsatisfactory in many cases. More recently it is recognized, that some of the neuro-endocrine compensatory processes associated with CHF are detrimental in the long run, and therefore potentially targets for drug treatment. This holds for the following neuro-endocrine mechanisms: 1) increased activity of the sympathetic nervous system and high plasma catecholamines, accompanied by down-regulation of beta 1- but not beta 2-receptors in the heart; 2) stimulation of the renin-angiotensin aldosterone system (RAAS), causing higher levels of renin, A II and aldosterone. The detrimental sequelae of both processes are even enhanced by their complex mutual interactions. Drug treatment aiming to reduce or suppress these processes and their negative results is potentially offered by: vasodilators, counteracting vasoconstriction, low dose selective beta 1-adrenoceptor blockers, which will not only impair tachycardia but also up-regulate cardiac beta 1-receptors and hence improve the inotropic response to catecholamines; aldosterone antagonists and ACE inhibitors counteracting the activated RAAS. The beneficial effect of the ACE inhibitors in CHF is well established and superior to that of classical vasodilators, since it additionally counteracts the enhanced RAAS activity. PMID- 2905475 TI - Dopamine D-2 receptors in the ventral tegmental area mediate behavioural and electrocortical sleep of dopaminergic drugs in rats. PMID- 2905476 TI - Receptor-mediated activation of tyrosine hydroxylase by corticotropin-releasing factor in striatal synaptosomes. PMID- 2905477 TI - Involvement of the Na+-H+ antiporter on the effect of protein kinase-C activation on dopamine synthesis in rat corpus striatum. PMID- 2905479 TI - Are D1 dopamine receptor agonists potential antidepressants? PMID- 2905478 TI - Debrisoquine oxidation in schizophrenic patients treated with neuroleptics. PMID- 2905480 TI - Head-twitch and forepaw-shake responses after single and repeated treatment with rolipram: interaction with noradrenergic and dopaminergic agonists and antagonists. PMID- 2905481 TI - Central and peripheral inhibition of exocrine pancreatic secretion by alpha-2 adrenergic agonists in the rat. AB - The effect of ST91, a clonidine derivative crossing poorly the blood-brain barrier, was compared to that of clonidine on exocrine pancreatic secretion in rats. The experiments were performed in anaesthetized rats after stimulation by a maximal dose of 2-deoxy-D-glucose, and in conscious rats under basal interdigestive conditions. In anaesthetized rats, the 2-deoxy-D-glucose-induced stimulation of pancreatic secretion was suppressed by clonidine but not by ST91, both injected subcutaneously. This effect of clonidine was not antagonized by prazosin, but was decreased by 70-100% (according to the variables measured) by yohimbine. The alpha-2 antagonists rauwolscine and corynanthine were less efficient than yohimbine, while idazoxan suppressed totally the effect of clonidine. In conscious rats, the basal interdigestive secretion was inhibited by ST91 and by clonidine. After sc injections, the potency of ST91 was about ten times smaller than that of clonidine, whereas after injections in the cerebral ventricles, ST91 was as potent as clonidine to inhibit pancreatic secretion. Most (70-90%) of the inhibition induced by sc ST91 and clonidine in conscious rats was suppressed by yohimbine or by prazosin. It is concluded that both ST91 and clonidine inhibit pancreatic secretion in rats, and that this effect has probably both central and peripheral components. The central effect involves alpha-2 receptors, while the peripheral effect may involve alpha-1 and alpha-2 receptors. PMID- 2905482 TI - Embryotoxicity of L-prolyl-L-leucyl-glycinamide, cyclo(1-amino cyclopentanecarbonyl-alanyl) and cyclo(glycyl-leucyl), new potential neuropeptides in chick embryos. AB - With the use of the method Chick Embryotoxicity Screening Test II (CHEST II), the potential neuropeptides L-prolyl-L-leucyl-glycinamide (MIF), cyclo(1-aminocyclo pentanecarbonyl-L-alanyl)[cyclo(Acp-Ala)] and cyclo(glycyl-L-leucyl)[Cyclo(Gly Leu)] were tested in the critical developmental periods of d 1.5 to 4 of chick embryogenesis in order to objectively examine their undesirable interactions with the developing morphogenetic systems of the brain, eye, face, body wall, limbs, trunk and heart. All compounds tested showed positive dose- and stage-response relationships. The body wall defects are the prevailing type of malformations. PMID- 2905483 TI - Effect of restraint stress and anxiolytics on 5-HT turnover in rat brain. AB - In male Tuck AHA rats, restraint stress had no effect on 5-hydroxytryptamine (5 HT) levels in the frontal cortex, amygdala, hypothalamus and hippocampus, but produced a significant increase in 5-hydroxyindoleacetic acid (5-HIAA) levels in the amygdala after 120 and 180 min, and in the hypothalamus after 180 min. This apparent increase in turnover was not paralleled by a concomitant increase in the rate of 5-HT synthesis, as determined by measuring the accumulation of 5 hydroxytryptophan (5-HTP) following inhibition of amino acid decarboxylase with m hydroxybenzylhydrazine (NSD-1015). 5-HTP accumulation was, however, increased in the frontal cortex after 180 min. In naive rats, buspirone (0.1-2.5 mg/kg, s.c.) produced a dose-dependent decrease in 5-HTP accumulation in all four brain regions, while chlordiazepoxide, in doses up to 10 mg/kg (s.c.) had no effect. The increase in 5-HT synthesis in the frontal cortex following 180 min restraint stress was inhibited by pretreatment with buspirone, when administered at 2.5 mg/kg (s.c.) 30 min prior to the stress period, but not by chlordiazepoxide at 10 mg/kg (s.c.). PMID- 2905484 TI - Influence of alpha 1-adrenergic receptor stimulation and phorbol esters on hepatic Na+/K+-ATPase activity. AB - The effects of the alpha 1-adrenergic agonist phenylephrine (PE) and the phorbol ester 4 beta-phorbolmyristate-acetate (PMA) on sodium pump function were studied in the rat liver. In order to distinguish between direct and indirect influences, ouabain-sensitive 86Rb uptake by intact liver slices was compared with ouabain sensitive Na+/K+-ATPase activity in plasma membranes isolated from PE and PMA perfused livers. At a buffer Ca2+ level of 2.5 mmol/l, PE (10 mumol/l) caused an initial stimulation of both 86Rb uptake and Na+/K+-ATPase activity followed at 5 min by a decrease in both activities. Both actions were blocked by the alpha 1 antagonist prazosin. The decrease in ouabain-sensitive Na+/K+-ATPase was paralleled by an increase in Mg2+ ATPase activity. At a Ca2+ level of 1.5 mmol/l, PE stimulation of 86Rb uptake and Na+/K+-ATPase was sustained, and the inhibitory component was not expressed. PMA (4 mumol/l) reduced 86Rb uptake and Na+/K+ ATPase and similar to PE, this inhibition was paralleled by an increase of Mg2+ ATPase activity. 4 alpha-PMA, which does not activate protein kinase C, failed to influence 86Rb uptake or Na+/K+-ATPase. These results demonstrate that PE and PMA effects on ouabain-sensitive 86Rb uptake are preserved in isolated membranes, indicating a direct influence on the Na+/K+-ATPase. A role for protein kinase C in modulating sodium pump activity is suggested. PMID- 2905485 TI - The structure of 2Zn pig insulin crystals at 1.5 A resolution. AB - The paper describes the arrangement of the atoms within rhombohedral crystals of 2Zn pig insulin as seen in electron density maps calculated from X-ray data extending to 1.5 A (1 A = 10(-10) m = 10(-1) nm) at room temperature and refined to R = 0.153. The unit cell contains 2 zinc ions, 6 insulin molecules and about 3 x 283 water molecules. The atoms in the protein molecules appear well defined, 7 of the 102 side chains in the asymmetric unit have been assigned alternative disordered positions. The electron density over the water molecules has been interpreted in terms of 349 sites, 217 weighted 1.0, 126 weighted 0.5, 5 at 0.33 and 1 at 0.25 giving ca. 282 molecules. The positions and contacts of all the residues belonging to the two A and B chains of the asymmetric unit are shown first and then details of their arrangement in the two insulin molecules, 1 and 2, which are different. The formation from these molecules of a compact dimer and the further aggregation of three dimers to form a hexamer around two zinc ions, follows. It appears that in the packing of the hexamers in the crystal there are conflicting influences; too-close contacts between histidine B5 residues in neighbouring hexamers are probably responsible for movements of atoms at the beginning of the A chain of one of the two molecules of the dimer that initiate movements in other parts, particularly near the end of the B chain. At every stage of the building of the protein structure, residues to chains of definite conformation, molecules, dimers, hexamers and crystals, we can trace the effect of the packing of like groups to like, aliphatic groups together, aromatic groups together, hydrogen-bonded structures, positive and negative ions. Between the protein molecules, the water is distributed in cavities and channels that are continuous throughout the crystals. More than half the water molecules appear directly hydrogen bonded to protein atoms. These are generally in contact with other water molecules in chains and rings of increasing disorder, corresponding with their movement through the crystals. Within the established crystal structure we survey next the distribution of hydrogen bonds within the protein molecules and between water and protein and water and water; all but eight of the active atoms in the protein form at least one hydrogen bond.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2905486 TI - Frequency-dependent selection. A discussion. 24 and 25 June 1987. PMID- 2905487 TI - Frequency-dependent selection in bacterial populations. AB - There are many situations in which the direction and intensity of natural selection in bacterial populations will depend on the relative frequencies of genotypes. In some cases, this selection will favour rare genotypes and result in the maintenance of genetic variability; this is termed stabilizing frequency dependent selection. In other cases, selection will only favour genotypes when they are common. Rare types cannot invade and genetic variability will not be maintained; this is known as disruptive frequency-dependent selection. Phage mediated selection for bacteria with novel restriction-modification systems is frequency-dependent and stabilizing. In mass culture, selection for the production of toxins and allelopathic agents is likely to be frequency-dependent but disruptive. This also occurs in selection favouring genes and transposable elements that cause mutations. Here I review the results of theoretical and experimental studies of stabilizing and disruptive frequency-dependent selection in bacterial populations, and speculate on the importance of this kind of selection in the adaptation and evolution of these organisms and their accessory elements (plasmid, phage and transposons). PMID- 2905488 TI - Frequency-dependent selection by predators. AB - Sometimes predators tend to concentrate on common varieties of prey and overlook rare ones. Within prey species, this could result in the fitness of each variety being inversely related to its frequency in the population. Such frequency dependent or 'apostatic' selection by predators hunting by sight could maintain polymorphism for colour pattern, and much of the supporting evidence for this idea has come from work on birds and artificial prey. These and other studies have shown that the strength of the observed selection is affected by prey density, palatability, coloration and conspicuousness. When the prey density is very high, selection becomes 'anti-apostatic': predators preferentially remove rare prey. There is still much to be learned about frequency-dependent selection by predators on artificial prey: work on natural polymorphic prey has hardly begun. PMID- 2905489 TI - Frequency-dependent predation, crypsis and aposematic coloration. AB - Frequency-dependent predation may maintain or prevent colour pattern polymorphisms in prey, and can be caused by a variety of biological phenomena, including perceptual processes (search images), optimal foraging and learning. Most species are preyed upon by more than one predator species, which are likely to differ in foraging styles, perceptual and learning abilities. Depending upon the interaction between predator vision, background and colour pattern parameters, certain morphs may be actively maintained in some conditions and not in others, even with the same predators. More than one kind of predator will also affect stability, and only slight changes in conditions can cause a transition between polymorphism and monomorphism. Frequency-dependent selection is not a panacea for the explanation of variation in animal colour patterns, although it may be important in some systems. PMID- 2905490 TI - The rare-male effect: what is its evolutionary significance? AB - Negatively frequency-dependent male mating success, the rare-male effect (RME), has been reported from many laboratory experiments, particularly with Drosophila spp. Problems with observer bias, lack of repeatability, with experimental design and with the analysis of data may indicate that the RME is considerably less well documented than has been supposed, even in the laboratory. Male competition is unlikely to be a common cause of the RME, except where there are behavioural differences between competing strains that result in lower competition between them than within them. A mixture of fixed female preferences seems the most likely cause, and further behavioural studies are required to investigate this mechanism. There is no convincing evidence that the RME is a consequence of frequency-dependent female preferences. An RME in the absence of negative assortment is not in general expected to lead to the avoidance of inbreeding because matings between relatives will not be reduced. Nor is it likely to contribute to the high levels of genetic polymorphism found in nature, because females would be required to base their mating preferences on genotypes at all or most loci, to show individual variation in respect of their preferences and to sum the information into an index of genomic rarity. Given the levels of polymorphism involved, all males are likely to be rare by some criterion. A varying direction of female preference, required for a two-sided RME and for the maintenance of genetic polymorphism, has yet to be reported from wild populations. The RME is therefore probably of limited evolutionary significance. Disassortative mating with respect to self-incompatibility alleles in plants, and possibly major histocompatibility complex (MHC) alleles in vertebrates, results in an RME, inbreeding avoidance and high levels of genetic polymorphism at these loci. PMID- 2905491 TI - Dynamics of some simple host-parasite models with more than two genotypes in each species. AB - A two-species genetic model of host-parasite interaction is used to study the dynamical consequences of varying the number of genotypes in each species, and the recombination rate in the host. With two genotypes in each species, the model's behaviour is very simple; there is either a stable interior equilibrium, a stable cycle or a smooth outward spiral toward the boundaries. But with three or more genotypes, complex cycles and apparently chaotic behaviour may arise over wide ranges of parameter values. Increasing the number of genotypes also tends to slow the rate of gene-frequency change. Recombination in the host does not affect the stability of the interior fixed point, but intermediate rates of recombination may give dynamic stability to an otherwise dynamically unstable pattern of cycling. Intermediate rates of recombination also tend to decrease the amplitudes of gene-frequency cycles in the host, which implies that they could promote the accumulation of genetic variation involved in complementary, antagonistic interactions with parasites. PMID- 2905492 TI - The evolution of aggression: can selection generate variability? AB - Three models--the war of attrition, the size game and the badges of dominance game--are described, in which natural selection can maintain genetic variability for aggression. The models differ in whether or not the traits that settle contests are costly in contexts other than fighting, and also in whether signals are used. It is concluded that contests will be settled by non-costly traits only if the value of the contested resource is small relative to the cost of fighting, and that 'honest' signalling of aggressiveness is stable only if individuals giving signals that are inconsistent with their behaviour suffer costs. The literature on 'badges of dominance' in birds is reviewed. New data on great tits, greenfinches and corn buntings show that there is plumage variability within age and sex that sometimes serves to settle contests, and that, in the first two species but not the third, the badges are uncorrelated with size, and settle contests only over trivial resources. PMID- 2905493 TI - Frequency-dependent sexual selection. AB - Sexual selection by female choice is expected to give rise to a frequency dependent sexual advantage in favour of preferred male phenotypes: the rarer the preferred phenotypes, the more often they are chosen as mates. This 'rare-male advantage' can maintain a polymorphism when two or more phenotypes are mated preferentially: each phenotype gains an advantage when it is rarer than the others; no preferred phenotype can then be lost from the population. Expression of preference may be complete or partial. In models of complete preference, females with a preference always mate preferentially. Models of partial preference are more realistic: in these models, the probability that a female mates preferentially depends on the frequency with which she encounters the males she prefers. Two different 'encounter models' of partial preference have been derived: the O'Donald model and the Charlesworth model. The encounter models contain the complete preference model as a limiting case. In this paper, the Charlesworth model is generalized to allow for female preference of more than one male phenotype. Levels of frequency dependence can then be compared in the O'Donald and Charlesworth models. The complete preference model and both encounter models are formulated in the same genetical terms of preferences for dominant and recessive male phenotypes. Polymorphic equilibria and conditions for stability are derived for each of the three models. The models are then fitted to data of frequencies of matings observed in experiments with the two-spot ladybird. The complete preference model gives as good a fit as the encounter models to the data of these and other experiments. The O'Donald and Charlesworth encounter models are shown to produce a very similar frequency-dependent relation. Generally, as females become less choosy, they express their preference with more dependence on male frequency, whereas the resulting selection of the males becomes less frequency dependent. More choosy females are more constant in expressing their preference, producing greater frequency dependence in the selection of the males. PMID- 2905494 TI - Frequency dependence and competition. AB - Intraspecific competition implies interaction among the individuals of a population, so natural selection on genotypic variation in characters related to the competition will necessarily be frequency dependent. Intraspecific antagonistic competition exhibits properties similar to other behavioural interactions between individuals. In exploitative intraspecific competition the interactions among individuals are less direct. Exploitation modifies the abundance of the various limiting resources according to the use of these resources by the individual members of the population. The amount of resource available to an individual is therefore a function of the phenotypes present in the population, through their density and frequency. PMID- 2905495 TI - Frequency-dependent selection and competition: empirical approaches. AB - When Darwin and Wallace first formulated the theory of evolution by natural selection, they were greatly influenced by the idea that populations tend to increase geometrically and rapidly outgrow the resources available to them. They argued that the ensuing competition among individuals would be a major agent of natural selection. Since their day, competition has become almost synonymous with the idea of natural selection or survival of the fittest. In this paper we examine the relation between competition and selection by using simple competition models, consider the interaction of density and frequency in determining competitive outcome, and review the literature on frequency-dependent competitive interactions among genotypes within populations. PMID- 2905496 TI - Relative roles of mutation and selection in the maintenance of genetic variability. AB - The extent and pattern of protein and DNA polymorphisms are discussed with emphasis on the mechanism of maintenance of the polymorphisms. Statistical studies suggest that a large proportion of genetic variability at the molecular level is maintained by a mutation-drift balance. At some loci, such as those for histocompatibility in mammals, however, a form of overdominant selection seems to be involved. In the presence of overdominant selection, polymorphic alleles may be maintained for tens of millions of years, so that the number of nucleotide differences between alleles is often very large, as in the case of self incompatibility alleles in plants. There are also an increasing number of examples in which an adaptive change of a morphological or physiological character is caused by a single nucleotide substitution. Nevertheless, these mutations seem to be a small proportion of the total nucleotide changes that contribute to genetic variability and evolution. Although there are many examples of frequency-dependent selection, this form of selection is apparently unimportant for the maintenance of genetic variability except in some special cases. Observations on the evolutionary change of DNA suggest that the driving force of evolution is mutation rather than selection. PMID- 2905497 TI - Frequency-dependent selection, metrical characters and molecular evolution. AB - Computer models of selection acting on a quantitative character show that a combination of frequency-dependent and stabilizing selection can maintain many polymorphisms among the genes that determine the character. The models also show that the random order of mutations can give rise to selectively driven stochastic effects that are sometimes more important than random genetic drift. They suggest simple explanations for patterns of divergence between populations and species, and for apparent discrepancies between the rates of morphological and molecular evolution. They point towards a selective theory of 'molecular clocks'. PMID- 2905498 TI - Effect of inhibitors of gamma-glutamyl transpeptidase on the uptake of glutamate and aspartate into cultured astroglial cells from the glycogen body and cerebral hemispheres of the embryonic chick. AB - Astroglial-like cells from the glycogen body and astroglia from the cerebral hemispheres of chick embryos cultured 6 days in vitro exhibit comparable values of L-glutamate and L-aspartate uptake. The uptake is significantly reduced by inhibitors of gamma-glutamyl transpeptidase. PMID- 2905499 TI - Dose-response curves of homovanillic acid in pre-frontal cortex and caudate following antipsychotic drugs: relation to clinical potencies. AB - Dose-response curves for the elevation of homovanillic acid (HVA) levels, determined by high performance liquid chromatography using electrochemical detection, in the pre-frontal cortex and caudate of rats after acute treatment with 12 antipsychotic drugs are presented. The order of potency in both brain regions was: haloperidol greater than or equal to fluphenazine greater than loxapine greater than trifluoperazine greater than thiothixene greater than molindone greater than clopenthixol greater than chlorpromazine greater than metoclopramide greater than thioridazine greater than clozapine greater than sulpiride. This ranking is roughly correlated with that based on clinical potencies. The relative elevation of the content of HVA was weaker in the pre frontal cortex than in the caudate for all drugs tested, except clozapine at a high dose. PMID- 2905501 TI - Benzodiazepine antagonist RO 15-1788 partly reverses some anxiolytic effects of ethanol in the mouse. AB - The effects of the benzodiazepine (BZD) receptor antagonist RO 15-1788 (3 mg/kg) on the anxiolytic properties of ethanol in mice confronted with a light/dark choice procedure and with the staircase test were investigated. RO 15-1788 reversed the effects of ethanol on some of the behavioural parameters without eliciting intrinsic effects when given alone. These data closely resemble those we previously obtained with several BZD receptor inverse agonists such as RO 15 3505, RO 15-4513 or beta-CCM. Since anxiogenic-like properties of low doses of RO 15-1788 have been identified by other authors, it is suggested that the antagonistic action of this drug against some of the behavioural effects of ethanol could be due to its being a partial BZD inverse agonist. PMID- 2905500 TI - Human studies on the benzodiazepine receptor antagonist beta-carboline ZK 93 426: antagonism of lormetazepam's psychotropic effects. AB - The effects of lormetazepam (0.03 mg/kg IV) a benzodiazepine (BZ) derivative in combination with ZK 93 426 (0.04 mg/kg IV) a beta-carboline, benzodiazepine receptor antagonist were evaluated in humans. Independently, the effects of ZK 93 426 on its own were investigated. A psychometric test battery to evaluate sedation (visual analog scales (VAS), anxiolysis (state-trait-anxiety inventory scale (STAIG X1) and cognitive functions [logical reasoning test (LR), letter detection test (LD)] was applied before and several hours after initiation of treatment. Multiple sleep latency test (MSLT), which measures day time sleepiness, was also applied. Vigilosomnograms analysed from standard EEG recordings were evaluated shortly before and for 1 h after treatment. Treatment started with an intravenous injection of either lormetazepam (LMZ) or placebo (PLA), which was followed 30 min later by administration of either ZK 93 426 or placebo; thus four treatment groups were created (PLA + PLA, LMZ + PLA, LMZ + ZK 93 426 and PLA + ZK 93 426). ZK 93 426 antagonized the sedative and hypnotic effect of LMZ as estimated by MSLT and vigilosomnograms, respectively. Impairment of cognitive functions (LR and LD) induced by LMZ was also antagonized by ZK 93 426. ZK 93 426 had no effect on the changes in the time estimation seen in the LMZ group. Furthermore, ZK 93 426 on its own increased vigilance (alertness) as measured by the vigilosomnogram. A competitive antagonism at the benzodiazepine binding site between ZK 93 426 and LMZ is suggested by their combination effects; the intrinsic activity of ZK 93 426 seems to be due to its weak partial inverse agonist component. PMID- 2905502 TI - The effects of haloperidol on the partial reinforcement extinction effect (PREE): implications for neuroleptic drug action on reinforcement and nonreinforcement. AB - The effects of haloperidol 0.1 mg/kg on the partial reinforcement extinction effect (PREE) paradigm at one trial a day, were examined. Two groups of rats were trained to run in a straight alley. The continuously reinforced (CRF) group received food reward on every trial. The partially reinforced (PRF) group was rewarded on a quasi-random 50% schedule. All animals were then tested in extinction. Haloperidol 0.1 mg/kg was administered in a 2 x 2 design, i.e., drug no drug in acquisition and drug-no drug in extinction. The PREE, i.e., increased resistance to extinction of partially reinforced as compared to continuously reinforced animals, was obtained in all four drug conditions. The administration of haloperidol in acquisition increased markedly resistance to extinction in CRF animals. The administration of the drug in extinction decreased resistance to extinction in both CRF and PRF animals. The results are explained in terms of two independent actions of haloperidol: the well-known effect of reduction in the effectiveness of reinforcement as well as enhancement of the effectiveness of nonreinforcement. PMID- 2905503 TI - Chronic administration of a selective dopamine D-2 agonist: factors determining behavioral tolerance and sensitization. AB - The locomotor stimulant effects of sustained administration of a potent and selective dopamine (DA) D-2 receptor agonist, [+]-4-propyl-9-hydroxynaphthoxazine (PHNO), in rats were assessed 24 h a day during 12 h light-dark cycles. PHNO was administered continuously with subcutaneous implants of Alzet osmotic minipumps (5 micrograms/h), for 12 h a day with modified osmotic minipumps (5 micrograms/h), or by daily injections (15 micrograms, SC). Tolerance was observed to occur only with 24 h continuous infusions and only during the light period. The other treatment regimens produced sensitization of the locomotor response. Daytime tolerance to continuous infusions of PHNO was reversed following reversal of the light-dark cycle. A normally 'arousing' stimulus also reversed (temporarily) daytime tolerance. The present results indicate that the temporal pattern of administration of DA agonists, the phase of the circadian cycle and environmental stimuli associated with arousal are important determinants of the behavioral consequences of long-term treatment. PMID- 2905504 TI - Behavioural influences on benzodiazepine tolerance: when do they occur and what do they mean? PMID- 2905505 TI - CNS effects of beta blockade: a comparative study. PMID- 2905506 TI - Information processing and maintenance dose requirements in schizophrenia. PMID- 2905507 TI - Psychotropic management of behavioral disorders after head trauma. AB - A rational basis for the psychopharmacologic management of behavioral disturbances after head trauma has been presented that is predicated on research in neurotransmitter changes that evolve subsequent to head trauma. The paucity of human studies in this area mandates the use of experimental models and evidence garnered from provocative challenges to suggest the underlying neurotransmitter profile in various behavioral abnormalities. Multiple neurotransmitter circuits exist that provide parallel, duplicate, and redundant systems for these behaviors. Certainly, alternative explanations could be offered for the examples cited above. Furthermore, measurement of neurotransmitter metabolite concentration in cerebrospinal fluid does not allow specific inferences to be made regarding topographic correlation and neurotransmitter function. Nor does it afford assessment of regional differences in psychotropic influence on neurotransmitter receptors. New imaging techniques (eg, positron emission tomography) will certainly aid in this determination. Current investigations, however, support the concept that neurotransmitter changes do occur after head injury, that these alterations exist during the time that "recovery" occurs, and that psychotropic agents influence this recovery process. Further research is needed to clarify neurotransmitter changes after head injury and to identify psychotropic intervention strategies that facilitate the recovery process. PMID- 2905508 TI - Psychobiologic aspects of the treatment of primary mania. PMID- 2905509 TI - In vitro lecithinase activity and sensitivity to 22 antimicrobial agents of Clostridium perfringens isolated from necrotic enteritis of broiler chickens. AB - Viable Clostridium perfringens ranging from 10(5) to 10(8) g-1 was detected in all of 88 intestinal content specimens of necrotic enteritis in broiler chickens. In vitro lecithinase activity and sensitivity to 22 antimicrobial agents were determined for the 88 isolates. The activities of lecithinase in the culture filtrate of isolates were estimated to be 0.5 to 4.0 AE ml-1 as alpha-antitoxin equivalent. With reference to antimicrobial activity penicillins and cephazolin showed excellent activity and no resistance; peptides, of the agents used as growth promoters, showed that all except bacitracin had low minimum inhibitory concentration levels (1.6 micrograms ml-1 or less) against this organism; polyethers of monensin, salinomycin and lasalocid were generally adequate in low concentrations while there was a high level of resistance to three tetracyclines in 90 per cent of the strains and all isolates were insusceptible to streptomycin of the aminoglycoside antibiotics. PMID- 2905510 TI - Fimbria-like adhesive factor (EAF 44) from verocytotoxigenic Escherichia coli of bovine origin. AB - An adhesin with fimbria-like properties was present in four strains of verocytotoxigenic Escherichia coli isolated from diarrhoeic calves in Brazil. PMID- 2905511 TI - [Secondary prevention of ischemic cardiopathy. Current problems and outlook]. PMID- 2905512 TI - [Clinical and prognostic correlations of clinically manifest ischemic cardiopathy and transient asymptomatic ischemia]. PMID- 2905513 TI - [Diagnostic criteria in left anterior bundle-branch block (hemiblock)]. PMID- 2905514 TI - [The significance of changes in the QRS complex in the severity of ventricular arrhythmia]. PMID- 2905515 TI - [Electrocardiographic aspects in patients with implanted cardiac pacemakers]. PMID- 2905516 TI - [Etiological classification of chronic hepatitis]. PMID- 2905517 TI - [Morphology and variation of the Berg bodies in chronic liver disease]. PMID- 2905518 TI - [Upper digestive hemorrhage in portal hypertension]. PMID- 2905519 TI - [Comparative study of the efficacy of De-Nol and ranitidine in treating duodenal ulcer]. PMID- 2905520 TI - [Vienna, the hard challenges of WHO]. PMID- 2905521 TI - Lithium therapy and prophylaxis in unipolar manic-depressive illness. PMID- 2905522 TI - [Dermatoglyphics in cryptorchism]. PMID- 2905523 TI - Clinical phenomenology. PMID- 2905524 TI - Genetics, immunology, and virology. PMID- 2905525 TI - Neurochemistry and neuropharmacology. PMID- 2905526 TI - Developmental dialectics. PMID- 2905527 TI - [Beta2-microglobulin in the blood serum in hemorrhagic fever with the renal syndrome]. PMID- 2905528 TI - The GABAA receptor: new insights from single-channel recording. AB - The GABAA receptor of mammalian neurons exists as a macromolecular complex incorporating several interacting components. These include a chloride-permeable ion channel and a recognition site for GABA. The binding of GABA molecules at the latter site triggers the transient opening of the chloride ion channel, resulting in a flow of charge which inhibits the generation of action potentials in the cell. The precise amount of charge passed during this event is modulated by ligand binding at at least three regulatory sites. These sites act as receptors for barbiturates, benzodiazepines, and certain convulsants. The extracellular patch clamp method has now been used to study the gating of chloride channels by GABA and the modulation of this process by drugs. Even in the absence of drugs, GABAA channels exhibit complex gating behavior, indicating the presence of multiple open and closed states and of substate conductance levels. GABAA channels from different preparations show considerable diversity in their detailed gating characteristics. In the presence of the barbiturate pentobarbital, GABAA channels open in prolonged bursts, consistent with the potentiating effect of this drug on macroscopic GABA responses. In contrast, the convulsant penicillin decreases charge transfer through open GABAA channels by shortening the average duration of the open state. Benzodiazepine receptor ligands exert complex effects on the GABAA channel. A general model of barbiturate and benzodiazepine potentiation of GABAA receptor responses is proposed. PMID- 2905529 TI - Dopamine receptors and the dopamine hypothesis of schizophrenia. AB - The discovery of neuroleptic drugs in 1952 provided a new strategy for seeking a biological basis of schizophrenia. This entailed a search for a primary site of neuroleptic action. The Parkinsonian effects caused by neuroleptics suggested that dopamine transmission may be disrupted by these drugs. In 1963 it was proposed that neuroleptics blocked "monoamine receptors" or impeded the release of monoamine metabolites. The neuroleptic concentration in plasma water or cerebrospinal fluid was of the order of 2 nM for haloperidol in clinical therapy. A systematic research was made between 1963 and 1974 for a primary site of neuroleptic action which would be sensitive to 2 nM haloperidol and stereoselective for (+)-butaclamol. Direct evidence that neuroleptics selectively blocked dopamine receptors occurred in 1974 with the finding that nanomolar concentrations of these drugs stereoselectively inhibited the binding of [3H] dopamine or [3H]-haloperidol. These binding sites, now termed D2 dopamine receptors (which inhibit adenylate cyclase), are blocked by neuroleptics in direct relation to the antipsychotic potencies of the neuroleptics. No such correlation exists for D1 receptors (which stimulate adenylate cyclase). Based on the fact that dopamine-mimetic drugs elicited hallucinations, and that neuroleptics caused rigidity, Van Rossum in 1966 had suggested a hypothesis that dopamine pathways may be overactive in schizophrenia. The D2-selective blockade by all neuroleptics (except the monoamine-depleting reserpine) provided strong support for the dopamine hypothesis. Further support now comes from postmortem data and in vivo positron tomographic data, both of which indicate that the density of D2 receptors are elevated in the schizophrenic brain. The postmortem data indicate a bimodal pattern with half the schizophrenics having striatal D2 densities of 14 pmol/g (control is 13 pmol/g) and the other half having 26 pmol/g. Current positron tomographic data indicate D2 densities of 14 pmol/g in control subjects, but values of 34 pmol/g in drug-naive schizophrenics. Future tests of the dopamine hypothesis of schizophrenia may entail an examination of the amino acid composition and genes for D2 receptors in schizophrenic tissue, an examination of the ability of the D2 receptor to become phosphorylated and to desensitize into the low-affinity state, and an examination of the interaction of D2 receptors with D1 receptors or other neurotransmitters. PMID- 2905530 TI - Epinephrine and norepinephrine modulate neuronal responses to excitatory amino acids and agonists in frog spinal cord. AB - The interaction of the catecholamines epinephrine (E) and norepinephrine (NE) (1.0-100 microM) and excitatory amino acids on motoneurons of the isolated superfused frog spinal cord was investigated by sucrose gap recordings from ventral roots. Exposure of the cord to E or NE 30 sec prior to application of L aspartate or L-glutamate reduced the motoneuron depolarizations produced by the amino acids. The reduction of responses to the mixed receptor agonists L glutamate and L-aspartate may be the result of opposite actions of the catecholamines on the activation of specific excitatory receptors by the amino acids. Thus, E and NE facilitated depolarizations caused by application of N methyl-D-aspartate (NMDA) and depressed those produced by quisqualate. The effect on NMDA responses appeared to be beta-adrenoceptor mediated because it was mimicked by the beta-agonist isoproterenol and blocked by propranolol. The effect on quisqualate depolarizations appeared to require activation of alpha 2 adrenoceptors; it was mimicked by the alpha 2-agonists clonidine and alpha methylnorepinephrine and antagonized by yohimbine and piperoxan. These results are important in understanding the actions of catecholamines on reflex transmission in spinal pathways which use excitatory amino acids as transmitters. PMID- 2905531 TI - Reversible shifts in the Ca2+-dependent release of aspartate and glutamate from hippocampal slices with changing glucose concentrations. AB - It is known that low glucose concentrations increase the aspartate and decrease the glutamate content of brain tissue both in vivo and in vitro. To see whether these changes occur in the transmitter compartment or not, the release of aspartate and glutamate evoked by electrical-field stimulation or by high K+ was followed in slices of rat hippocampus superfused with 5 or 0.2 mM glucose. Superfusion with 0.2 mM glucose increased the evoked release of aspartate about ten times and that of glutamate about threefold. This shift in the ratio of aspartate to glutamate released was accompanied by a similar increase in the relative amount of aspartate contained in the slices. The high evoked release of aspartate and glutamate was well maintained, provided 0.5 mM glutamine was added to the medium. Changing the concentration of glucose after the first period of stimulation rapidly altered the relative amounts of aspartate and glutamate released but not the enhanced release of glutamate. The large evoked release of both aspartate and glutamate in 0.2 mM glucose was almost entirely Ca2+ dependent. The relative amounts of aspartate and glutamate released by 50 mM K+ also changed when the glucose concentration was reduced. Results suggest two effects of low glucose concentrations: an increase in the overflow of synaptically released glutamate due to a decreased uptake and an increase in the proportion of aspartate to glutamate formed and released from the transmitter pool. These observations are consistent with the interpretation that these two transmitters can be released in different proportions from the same terminals. PMID- 2905532 TI - Localization of serotonin 5-HT2 receptors in living human brain by positron emission tomography using N1-([11C]-methyl)-2-Br-LSD. AB - N1-([11C]-Methyl)-2-Br-LSD ([11C]-MBL) has been developed as a positron emission tomography (PET) imaging agent for serotonin 5-HT2 receptors. In vitro receptor binding assays with nonradioactive MBL show high-affinity binding to serotonin 5 HT2 receptors (Ki = 0.5 nM), a secondary interaction of 8-fold lower affinity with dopamine D2 receptors, and low-affinity interactions with alpha 1-adrenergic as well as serotonin 5-HT1 receptors. Intravenous injection of [11C]-MBL in a baboon led to selective labeling of cortical regions that was markedly blocked by prior administration of ketanserin, a selective 5-HT2 receptor antagonist. Clinical trials with [11C]-MBL have been conducted in seven normal human volunteers, and the regional distribution of radioactivity in the brain was distinctly serotonergic. Labeling was highest in frontal, temporal, and parietal cortex with lower levels observed in caudate and putamen. The tracer rapidly washed from the cerebellum and the low levels of activity in this brain region were used to define nonspecific binding. The maximum specificity was reached between 30 and 60 minutes postinjection when frontal cortex to cerebellum ratios ranged from 1.7 for a 52-year-old male to 2.7 for a 30-year-old male. In agreement with previous studies, a trend towards lower ratios (lower serotonin 5 HT2 receptor levels) was observed in older volunteers. These studies indicate that [11C]-MBL is a selective radioligand that can be used to monitor serotonin 5 HT2 receptor densities in vivo in most regions of the human brain. PMID- 2905533 TI - Modification of 5-HT neuron properties by sustained administration of the 5-HT1A agonist gepirone: electrophysiological studies in the rat brain. AB - The sustained administration of the 5-HT1A agonist gepirone (15 mg/kg/day, s.c.) in the rat produced an initial decrease of the firing activity of dorsal raphe 5 HT neurons which was followed by a progressive recovery to normal after 14 days of treatment. At this point in time, the effect of intravenous lysergic acid diethylamide (LSD) on the firing activity of 5-HT neurons was markedly reduced, whereas those of 8-hydroxy-2-N,N-propylamino-tetralin (8-OH-DPAT) and of gepirone were unchanged; however, the responsiveness of 5-HT neurons to direct microiontophoretic application of 5-HT, LSD, 8-OH-DPAT, and gepirone, but not of GABA, was reduced. The responsiveness of postsynaptic dorsal hippocampus pyramidal neurons to 5-HT, 8-OH-DPAT, and gepirone was not altered by the 14-day gepirone treatment. The effectiveness of the electrical stimulation of the ascending 5-HT pathway in reducing pyramidal neuron firing activity was not significantly modified in rats treated with gepirone for 14 days. Furthermore, this treatment did not alter the function of the terminal 5-HT autoreceptor. It is concluded that the progressive restoration of the firing activity of 5-HT neurons, due to a desensitization of the somatodendritic 5-HT autoreceptor, combined with the direct activation of normosensitive postsynaptic 5-HT1A receptor by gepirone, should result in an augmented tonic activation of postsynaptic 5-HT1A receptors. The progressive appearance of this phenomenon would be consistent with the time course of the clinical anxiolytic, and possibly antidepressant, effects of gepirone. PMID- 2905534 TI - Hormonal regulation of somatostatin messenger RNA. AB - The ability of gonadal steroids to regulate the expression of the somatostatin gene in several regions of the CNS was investigated with in situ hybridization histochemistry. The amount of somatostatin mRNA was found to be significantly decreased 2-3 weeks after ovariectomy or orchidectomy in the periventricular hypothalamus, the ventromedial nucleus of the hypothalamus, and the medial and central nuclei of the amygdala. Treatment of gonadectomized rats with estradiol benzoate or testosterone enanthate reversed this decrease in somatostatin mRNA. No significant effect was noted in the cerebral cortex or bed nucleus of the stria terminalis. In some regions, there was a high degree of convergence between the distribution of neurons containing estrogen/androgen receptors and somatostatin neurons that were responsive to gonadectomy. These results suggest that sex steroids regulate the expression of somatostatin through an action at the level of transcription. PMID- 2905535 TI - Effects of alpha 1 adrenoceptor activation on the excitability of primary afferent terminals of the sural nerve in the spinal cord of the cat. PMID- 2905536 TI - Peptide- and transmitter-containing neurons in the mediobasal hypothalamus and their relation to GABAergic systems: possible roles in control of prolactin and growth hormone secretion. AB - Indirect immunofluorescence histochemistry was used to study the relation among GABAergic, catecholaminergic, cholinergic, and peptidergic neurons in the rat mediobasal hypothalamus. By employing a direct double-labelling procedure using sheep antiserum against glutamic acid decarboxylase (GAD), mouse monoclonal and rabbit antibodies to neurotensin (NT) and rabbit antisera to tyrosine hydroxylase (TH), choline acetyltransferase (ChAT), galanin (GAL), growth hormone-releasing factor (GRF), or somatostatin (SOM), it was demonstrated that GAD-positive fibers and terminals in the external part of the median eminence co-contained immunoreactivity for TH, NT, GAL or GRF, but not for SOM. In the internal part of the median eminence-infundibular stalk, GAD-positive/NT-, GAL-, and GRF-negative and GAD-positive/TH-positive fiber plexa were shown. When a recently developed direct triple-labelling procedure with biotin-conjugated mouse secondary antibodies in conjunction with diethylaminocoumarin (DAMC)-conjugated avidin was employed, presence of GAD/GAL/NT- as well as GAD/GRF/NT-containing varicosities could be demonstrated close to hypophysial portal vessels. In colchicine pretreated animals, GAD was shown to coexist with TH, NT, or GAL in cell bodies in both the dorsomedial and ventrolateral domains of the arcuate nucleus, but with GRF only in the ventrolateral division. ChAT-positive neurons in the ventrolateral region were also TH-positive. In the ventrolateral arcuate nucleus, triple-labelling followed by elution-restaining showed GAD/NT/GAL/TH immunoreactivities in the same cells. Similarly, double-labelling with two following elution-restaining steps showed several NT/GAL/GRF/TH-containing cell bodies in this part of the arcuate nucleus. GAD-positive cells in the anterior hypothalamic periventricular area and fibers in the pituitary neurointermediate lobe were also TH-positive. The results demonstrate complex patterns of storage of chemical messengers in neurons of the arcuate nucleus-median eminence complex. Possible neuroendocrine interactions of these systems in the control of prolactin and growth hormone secretion are discussed. PMID- 2905537 TI - Three-dimensional structure of bidirectional, excitatory chemical synapses in the jellyfish Cyanea capillata. AB - Neurons in the ectoderm of the perirhopalial tissue of the jellyfish Cyanea capillata were exposed and fixed for electron microscopy under conditions designed to minimize exocytosis of synaptic vesicles. The structure of the bidirectional chemical synapses that connect neurons was examined and the three dimensional organization of these synapses was determined from reconstructions of serial sections. Synapses were characterized by the accumulation of a relatively few, large synaptic vesicles. These lie in a single layer against the terminal membrane of each terminal. The cytoplasmic side of the vesicles in any one terminal was covered by a single, large, perforated cisternal sheet. In addition, there were numerous smaller, bulbous cisternae that intermingled with the vesicles in the terminal. The structure of any one terminal was mirrored by that of the opposite terminal of the pair. The organization of these synapses is discussed from the viewpoint of cnidarian synapses in general. PMID- 2905538 TI - Reciprocal zones of excitation and inhibition in the neostriatum. AB - Single-unit activity was recorded in the rat neostriatum at different distances from the point of an infusion of either glutamate or serotonin. In each case, firing rate at the distant site (0.8-1.5 mm) was the mirror image of that at the near site (0.1-0.3 mm). These reciprocal changes were blocked by a subsequent injection of haloperidol, a dopamine antagonist. It appears that a lateral inhibitory network, intrinsic to the neostriatum and possibly modulated by dopamine, plays an important role in the operation of the neostriatum. PMID- 2905539 TI - Properties of two classes of rat brain acidic amino acid receptors induced by distinct mRNA populations in Xenopus oocytes. AB - The Xenopus laevis oocyte expression system was used to study the molecular composition of mRNAs encoding acidic amino acid (AA) receptors from rat brain. Xenopus oocytes injected with poly(A) mRNA express two general classes of AA receptors. One class consists of AA-gated cation channels. Responses are evoked by N-methyl-D-aspartate (NMDA), by kainate, and to a lesser extent by L-glutamate or quisqualate. The second class of receptor is coupled to an intracellular second messenger pathway activating an oocyte-encoded Ca2+-activated Cl- conductance. This second messenger-coupled AA receptor can be activated by L glutamate or quisqualate. DL-2-amino-5-phosphonopentanoic acid and D-alpha aminohexanedioic acid inhibit the AA-gated cation conductances activated by NMDA or kainate with different potencies but do not inhibit the second messenger coupled AA receptor. Responses to NMDA are enhanced by micromolar level of glycine and are inhibited by Mg2+, Zn2+, or MK-801. Dose-response analysis reveals that the AA-gated cation conductance activated by kainate requires the binding of two agonist molecules. To study the molecular composition, the mRNAs were size-fractionated by denaturing agarose gel electrophoresis. About 20-fold purification in specific activity (nA/ng of mRNA injected) of mRNAs encoding the second messenger-coupled AA receptor was achieved. In contrast, only a slight enrichment of the mRNAs encoding the AA-gated channel was observed. This suggests that the second messenger-coupled AA receptor is encoded by a single size class of mRNA, whereas the AA-gated cation channel(s) is encoded by multiple species of mRNAs or by mRNAs whose size distribution is heterogeneous. PMID- 2905540 TI - N-methyl-D-aspartate receptor-mediated component of synaptic responses to single pulse stimulation in rat hippocampal slices. PMID- 2905541 TI - [Immunoregulatory disorders and activation of the immune system in dilated cardiomyopathy]. AB - The level of immunoregulatory lymphocytic subpopulations (CD3-, CD4-, CD8-cells, CD4/SD8 ratio, IaDr-positive cells, SD16-cells), lymphocyte natural cytotoxicity (NCT), the concentration of serum interferon (IF), beta 2-microglobulin (beta 2 M) and neopterin were investigated in 30 patients with dilatative cardiomyopathy (DCMP). Immunoregulatory lymphocytic subpopulations were defined by indirect immunofluorescence using monoclonal antibodies to differentiating markers of BMA and OKT series. A decrease in SD4/SD8 ratio less than 1 was observed in 10 patients, an increase in SD4/SD8 ratio over 2.3 was observed in 5 patients. A significant rise of IaDr-positive cells, a decrease in NCT, an increase in the concentration of IF, beta 2-M and neopterin were observed. There was correlation of an increase in IF concentration, the number of IaDr-positive cells and an increase in the level of neopterin and beta 2-M. Signs of activation of the immune system were more frequently noted in patients with a decreased (less than 1) or increased CD4/CD8 ratio. The role of disorders of immunoregulation and activation of the immune system in DCMP pathogenesis was discussed. PMID- 2905542 TI - [Evaluation of pump function of the heart in patients with occlusive diseases of the abdominal aorta and ischemic heart disease based on radionuclide ventriculography]. AB - Altogether 56 patients with occlusive abdominal aortic lesions and concomitant CHD were examined by radionuclide ventriculography on a nuclear stethoscope. Suppression of left ventricular systolic and diastolic function was noted in the patients with CHD and arterial hypertension. Investigations of cardiohemodynamics using the above method made it possible to identify patients with limited functional cardiac reserve, to predict possible myocardial complications, and to take preventive measures before, during and after reconstructive interventions on the abdominal aorta. PMID- 2905543 TI - Effects of exposing rat embryos in utero to physical or chemical teratogens are expressed later as enhanced induction of heat-shock proteins when embryonic hearts are cultured in vitro. AB - In order to get more insight into the effects of teratogens on developing embryos, we investigated the protein synthesis patterns of the target organs isolated from teratogen-treated embryos. Rat embryos were either irradiated in utero with either 252Cf fission neutrons or 60Co gamma rays on day 8 of gestation or treated in utero with a bis(dichloroacetyl)diamine (a chemical teratogen) on days 9 and 10. Hearts were removed from the embryos on day 12 and were incubated in vitro at 37 degrees C in the presence of [35S]methionine for up to 8 hr. The newly synthesized labeled proteins were then analyzed qualitatively by two dimensional polyacrylamide gel electrophoresis. Enhanced and prolonged induction of a family of heat-shock (stress) proteins with a molecular weight of about 70,000 (SP70s) was observed as compared with those of controls. Among the teratogen-treated hearts, those with gross malformations already detectable at this early stage showed especially higher inductions of SP70s than did the others. The abnormal expression of SP70s observed in the present study appears to be a reflection of persisting cellular (tissue) damage inflicted by the teratogens, and the extent of the induction may be indicative of the degree and/or type of the damage. Such persisting defects in surviving cells, manifested by abnormal induction of SP70s in the present study, might be related to malformation of embryonic hearts. PMID- 2905544 TI - Evaluation of the developmental toxicity of nicotine and cotinine with frog embryo teratogenesis assay: Xenopus. AB - The teratogenic potential of nicotine and a primary metabolite, cotinine, was examined with FETAX (Frog Embryo Teratogenesis Assay: Xenopus). Early embryos of Xenopus laevis were exposed for 96 hr to nicotine or cotinine in two separate static renewal tests of each compound without addition of the metabolic activation system (MAS). Two static renewal tests of nicotine with the MAS were also conducted. Addition of the MAS to nicotine reduced the LC50 from an average of 136 to 20 mg/L. However, the EC50 (malformation) was increased from 0.4 to 5.8 mg/L upon activation. The LC50 and EC50 values for cotinine averaged 4,340 and 720 mg/L, respectively. Based on mortality/malformation index values, growth end points, and the types and severity of the induced malformations, nicotine and cotinine scored as potential teratogens. Metabolism of nicotine to more polar metabolites increased the nicotine concentration required to induce terata. The results are indicative of the versatility of FETAX in developmental toxicity testing. PMID- 2905545 TI - Sister chromatid exchange in human lymphocytes exposed to ascorbic acid and the cancer chemotherapeutic agent 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea. AB - This study examines sister chromatid exchange (SCE) induction by ascorbate, a weak in vitro SCE inducer which acts through free radical intermediates, and low doses of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), a potent SCE inducer which acts primarily through DNA interstrand cross-links. A small dose dependent increase in SCE was observed in human peripheral lymphocytes exposed to ascorbate in the 0.5-10 mM dose range for 59 hours, with significant slowing of cell cycle kinetics at concentrations at and above 5 mM. CCNU concentration was selected to approximate the maximal increase in SCE induced by ascorbate. SCE frequencies in cells exposed sequentially to both agents were not significantly different from expectations under an additivity-of-effect model based on SCE response to each agent individually. Despite clear differences in the types of lesions induced, ascorbate and CCNU appear to act independently to induce SCE in a manner consistent with, though not exclusive to, Painter's replicon cluster model. PMID- 2905546 TI - Induction of estrogen receptor, peroxidase activity, and epithelial abnormalities in the mouse uterovaginal epithelium after neonatal treatment with diethylstilbestrol. AB - Neonatal female NMRI mice were treated with daily doses of 10(-2) or 5 micrograms diethylstilbestrol (DES) on one or more of days 1-5 after birth. Using immunohistochemical techniques and a monoclonal antibody to the estrogen receptor, we demonstrated an estrogen-induced precocious appearance of receptor protein in the nuclei of the uterovaginal epithelium. High levels of peroxidase activity and a pronounced stromal infiltration with peroxidase positive cells occurred in the uterine cervix and upper vagina after estrogen treatment. This regional restriction in peroxidase activity was similar to the regional restriction for estrogen-induced epithelial abnormalities (heterotopic columnar epithelium, adenosis). A combined treatment with DES and corticosterone depressed peroxidase activity but not to the control level. The distribution of abnormal epithelium was similar in DES- and DES-corticosterone-treated females. The conclusion is that neonatal estrogen treatment induces an epithelial receptor for estrogen and a high level of cervical peroxidase activity, but the relationship between these parameters and the appearance of abnormal cervicovaginal epithelial changes could not be settled in the present study. PMID- 2905547 TI - Effects of sodium azide on sea urchin embryos and gametes. AB - Sodium azide (SA) was tested on sea urchin embryos and gametes (Paracentrotus lividus). Developing embryos were exposed to SA (10(-6) to 10(-3) M) up to pluteus larval stage, or for shorter intervals before or after hatching. Developmental defects in SA-exposed embryos consisted mainly of gut abnormalities, without any detectable differences between pre- or post-hatch exposed embryos. SA-induced damage to gut was exerted during gastrulation, as evident by lectin binding of extracellular matrix. No mitotic damage was observed in SA-exposed embryos, nor could pH-related variations be detected in SA-induced embryotoxicity at pH's ranging from 8 to 6. Concurrently, no effect ensued in the exposure of unfertilized eggs to SA (10(-5) to 10(-2) M) both in terms of fertilization success and of offspring quality. When sperm were suspended in filtered seawater at pH's ranging from 8 to 6, and SA levels ranging from 10(-5) to 10(-2) M, fertilization success of SA-exposed sperm appeared to be modulated by pH, by displaying three distinct dose-response trends at pH 8, 7, or 6. The consequences of sperm pretreatment on offspring quality failed to show any significant SA-induced changes on larval malformations or mortality, while confirming the previously reported pH-induced increase of developmental defects in the offspring of acid-exposed sperm (Pagano et al.: Teratogenesis Carcinogen Mutagen 5:113-121, 1985). PMID- 2905548 TI - Relationship of periventricular overgrowth to hydrocephalus in brains of fetal rats exposed to benomyl. AB - Benomyl, a benzimidazole fungicide, was administered by gavage to pregnant Sprague-Dawley rats in a daily dose of 62.5 mg/kg of maternal body weight beginning at gestational day (GD) 7. Fetuses examined histologically at GD16 or GD20 revealed a high incidence of craniocerebral anomalies--82.6% of those examined at GD16 and 100% of those examined at GD20. Hydrocephalus occurred in 65.2% of fetuses examined at GD16 and in 58.8% at GD20 but was more severe in the GD20 fetuses. A second common anomaly, termed periventricular "overgrowth" (PVO), consisted of subependymal cell masses that in some fetuses obliterated normal subcortical structures. PVO occurred in 34.8% of fetuses examined at GD16 and 76.5% at GD20. The size of the subependymal masses and the regions involved were considerably greater in the GD20 than the GD16 fetuses. Less common anomalies in the GD20 fetuses were periventricular necrosis (41.2%), a single fetus with exencephaly and another with porencephaly. In the majority of malformed fetuses, the severity of hydrocephalus did not parallel the severity of PVO around the lateral and third ventricles. PVO involved tissues surrounding the cerebral aqueduct in 17.4% of GD16 fetuses and 38.2% of GD20 fetuses. This "overgrowth" distorted the cerebral aqueduct in a large number of fetuses with ventriculomegaly, and at GD20 moderate and severe ventriculomegaly was in every instance associated with a narrow or completely occluded cerebral aqueduct. These relationships suggest that PVO in the midbrain may play a role in the production of aqueductal stenosis and hydrocephalus in this experimental model. PMID- 2905549 TI - [European Community Workshop on the Perinatal and Heterosexual Transmission of HIV. London, 19-21 September 1988]. PMID- 2905550 TI - [Use of insulin and neuroleptics in treating schizophrenics]. PMID- 2905551 TI - [Gamma-glutamyltransferase activity in the serum and the mean-cell erythrocyte volume of patients with chronic ethylism and chronic liver diseases (preliminary report)]. AB - The dynamics of the enzyme gamma-glutamyltransferase (gamma GT) was followed up in 34 patients: 17 patients with liver cirrhosis, 9 patients with chronic hepatitis and 8 patients with liver steatosis. In the patients with alcoholic cirrhosis the activity of gamma GT rapidly fell in hospital conditions which is related to the forced abstinence. In the cirrhotic patients with nonalcoholic etiology no changes in gamma GT activity were found. In the patients with chronic hepatitis and liver steatosis with alcoholic etiology the gamma GT activity resembled that of alcoholic cirrhotic patients. The gamma GT activity fell most sharply in the patients with liver steatosis which is explained by the mild and reversible liver lesions characteristic for this disease. The mean erythrocyte volume determined by electronic blood cell counter shows a tendency toward macrocytosis in all chronic alcoholic patients. Macrocytosis is also found by ordinary microscopic examination of the blood cells. PMID- 2905552 TI - [Molecular genetic analysis of autoantibody production in systemic lupus erythematosus]. AB - This review summarizes studies from our and other laboratories attempting to define the molecular and clonotypic origin of autoantibodies that typify systemic autoimmune diseases such as lupus and rheumatoid arthritis. Comparative restriction fragment length polymorphism (RFLP) studies investigating the immunoglobulin (Ig) germline gene organization in lupus-prone strains of mice suggested that the disease can develop in different Ig heavy (H) and light (L) chain haplotypes, and that the Ig germline genes in lupus mice are probably normal. Analysis of the Ig gene segments expressed in monoclonal autoantibodies from autoimmune mice revealed that similar, and in some instances even identical, gene segments are expressed in autoantibodies and in antibodies to exogenous antigens, and that anti-self and anti-non-self responses are encoded by the same, or at least an overlapping germline gene repertoire. A large variety of Ig variable (V), diversity (D), and joining (J) gene segments can encode autoantibodies with different specificities, and both germline genes and somatically-mutated genes can be expressed in such antibodies. PMID- 2905553 TI - [Allergy to topical antihistamines--discrepancy between the literature and clinical practice]. AB - In a prospective study, 100 patients suffering from allergic contact dermatitis were tested for allergy to antihistamines. Diphenhydramine was chosen as test substance because it is the most widely used topical antihistamine in Europe and is, moreover, prescribed for several indications. Not one of the 100 patients proved to react positively on patch testing. The bad reputation among allergists of topically administered antihistamines, which is based on reports in the American literature claiming a high risk of epicutaneous sensitization, thus appears unjustified on the basis of our own data and the lack of European reports of this problem. The adverse findings in the USA may be due to their frequent use of a particularly potent contact sensitizer as emulsifier in topical preparations in general and antihistamines in particular. PMID- 2905554 TI - [Therapeutic possibilities in terminal heart failure]. AB - The severe and terminal cardiac insufficiency with myogenic failure and severe neurohumoral dysregulation means a problem situation in the chronically progressive or acute form of the course. The medicamentous treatment in form of the basis therapy with glycosides and saluretics may be improved by vasodilators or/and adrenergic agonists. In most cases we succeed in stabilizing the cardiovascular situation once to several times. As a rule the maximum stress only little increases. The neurohumoral dysregulation remains in different form apart from the basic disease which is no more to be corrected. Thus, in principle the vicious circle is closed. Whether the group of the so-called new inotropic and vasodilating pharmaca may essentially change the prognosis due to better influences on cardial and vascular and neurohumoral, respectively, dysfunctions, is not yet to be answered. A distinct alternative from the aspect of the cardiovascular function gives only the cardiac transplantation. The artificial heart and ventricular assist-systems, respectively, are accepted for the bridging over up to the cardiac transplantation. The hitherto existing state of development does not yet correspond to the imaginations of a pump regulated according to the needs, disregarding material, coagulation and energy problems. PMID- 2905555 TI - [Interaction of chronic inhibition of the angiotensin-converting enzyme and the sympathetic system: effect of added sodium chloride load]. PMID- 2905556 TI - [An attempt to optimize the diagnosis of rejection after allogeneic kidney transplantation using urinary enzymes and multivariate statistics]. PMID- 2905558 TI - [Lab technicians had a congress in Japan--Ulla-Britt will be Chairperson in 1990]. PMID- 2905557 TI - [Intracellular signalization: biological and medical aspects of the problem]. PMID- 2905559 TI - [The drug addict in prison: Medical response and its limitations]. AB - Over the past twenty years, the proportion of drug dependent inmates has risen dramatically in the prisons of Western Europe. In the Geneva romand prison, where about 30% of entries present problems of opiate abuse and dependence, treatment of withdrawal symptoms with decreasing doses of methadone over a period of 5-10 days has been available since 1974. The rational of this treatment policy is to limit immediately disabling symptoms during the stressful period following imprisonment, when the prisoner has to make important decisions concerning the criminal proceedings in which he is involved. On the other hand, methadone maintenance treatment is not provided within the prison, even for patients on methadone maintenance programs prior to imprisonment. This paper traces the evolution of withdrawal treatments with methadone over the period 1974-1987 in relation to the total number of entries, the age and sex distribution. During the three year period 1985-1987, we found that 6% of prisoners had received at least one course of withdrawal treatment. Many drug dependent individuals have repeated arrests: we found that 27% of those receiving withdrawal treatment in a three year period had more than one treatment. The frequency of suicidal gestures (including wrist slashing) and suicide was not greater during the withdrawal phase than at other times. A number of therapeutic approaches to opiate withdrawal now exist. No method seems clearly to be the treatment of choice within the prison environment. Arrest and imprisonment imply enforced withdrawal in a context of conflict and stress without the possibility of close medical supervision or psychological support.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2905560 TI - [Neurobiologic aspects of coping behavior]. AB - Psychosomatic thinking in medicine is emphasized by progressive integration of neurobiologic and psychologic (psychoanalytic) results. In recent years data pertaining to the interface between neurosciences and behavioral sciences had been presented. Some of the results in the fields of neuroanatomy, neurobiochemistry, endocrinology and psychoneuroimmunology corresponding to coping-processes are presented. PMID- 2905561 TI - [Toward the 8th All-Union Congress of Neuropathologists, Psychiatrists and Drug Abuse Specialists]. PMID- 2905562 TI - [The compensatory function of a GABA shunt in brain energy metabolism in measured craniocerebral trauma in rats]. AB - A severe compression craniocerebral trauma was induced in rats under short-term halothane anesthesia. The activity of pyruvate and 2-oxoglutarate dehydrogenase complexes reduced significantly in the tissue of the damaged hemisphere, ALT activity increased sharply, AST activity grew slowly, the production of GABA in the glutamate decarboxylase reaction was slightly inhibited and its utilization in the GABA transaminase reaction was clearly accelerated. The GABA level in the nerve tissue showed a tendency to reduce, while the glutamate level had a tendency to increase. The observed changes are evidence that the inclusion of the GABA skeleton in the reaction of further oxidation intensifies, which may be of significance in compensation of the transport of the energetically oxidizing succinate and, possibly, in the formation of endogenous GABA possessing a stress relieving effect. PMID- 2905563 TI - [Surgical therapy of sporadic and familial pheochromocytoma]. AB - From 1975 through 1987, 54 patients underwent operations for pheochromocytoma (PCC): 37 patients for sporadic unilateral adrenal PCC, 9 for bilateral and familial PCC, and 4 patients for paraganglioma. In 4 additional patients, laparotomy failed to discover the reason for hypercatecholaminemia. There were no operative mortality and a low morbidity for unilateral (n = 43) as well as for bilateral adrenalectomy (n = 6). To avoid hormone replacement therapy after bilateral total adrenalectomy at least for some years, unilateral instead of bilateral adrenalectomy was preferred to be the initial surgical procedure of choice for familial and MEN-IIA-associated unilateral adrenal PCC. Autologous transplantation of the adrenal cortex were performed in 2 patients after bilateral adrenalectomy. 6 months postoperatively, the transplants were vital as proved by light-microscopy, but sufficiently functioning only in 1 patient. PMID- 2905564 TI - Morphology of the adrenal medulla indicating multiple neuroectodermal abnormalities in pheochromocytoma patients. AB - 25 of 85 (29.4%) consecutive patients operated on for pheochromocytoma had other neuroectodermal abnormalities. Medullary thyroid carcinoma was the most common associated neuroectodermal abnormality followed by von Recklinghausen's neurofibromatosis. Other abnormalities were intracranial tumors, parathyroid hyperplasia and midgut carcinoid. The adrenal medulla was studied to find out morphological characteristics in patients with associated neuroectodermal abnormalities. All patients with multiple pheochromocytomas (n = 7) and all patients with hyperplasia of the extratumoral adrenal medulla (n = 13) had other neuroectodermal abnormalities. It is important to detect the associated neuroectodermal abnormalities because they can be lethal. Patients with associated neuroectodermal abnormalities often have hereditary syndromes. PMID- 2905565 TI - Experience with vecuronium during long-lasting surgery. AB - Our knowledge of the possible cumulative properties of vecuronium is limited. Previous studies have shown a tendency towards an increased duration of effect, a slightly prolonged recovery time, as well as an increased variation in duration of effect. We have studied 15 patients scheduled for middle-ear surgery. During i.v. N2O-O2 anaesthesia the twitch response of the adductor pollicis muscle was recorded after supramaximal stimulation of the ulnar nerve at the wrist. Prior to tracheal intubation a bolus dose of vecuronium was given (0.08 mg/kg body weight). During surgery supplementary doses of 0.02 mg/kg body weight were given at a train-of-four (TOF) ratio of 0.25. The duration of effect (DUR-IT-25) and recovery time from a TOF ratio of 0.10 to 0.25 (Recovery-IT-10-25) were recorded. When comparing 10 iteration doses, the mean DUR-IT-25 in the 15 patients studied showed only minor variations (n.s.). Each patient had a near constant interval between the iteration doses; however, a noteworthy variation between individuals was found. Recovery-IT-10-25 was 250 +/- 80 (mean +/- s.d.) 240 +/- 80 and 260 +/ 80 s comparing the second, sixth and tenth iteration doses, respectively. In conclusion, the duration of effect varied considerably between patients. Each patient showed, however, a near constant iteration interval and a recovery time with only small variations. This indicates that cumulation is unlikely to exist following repetitive administration of vecuronium of 0.02 mg/kg body weight. PMID- 2905566 TI - QT interval of the ECG, heart rate and arterial pressure using five non depolarizing muscle relaxants for intubation. AB - The QT interval, heart rate and arterial pressure were measured during anaesthetic induction in 186 patients without cardiovascular diseases or any preoperative drugs. The study was randomized and double-blind. The patients were premedicated with either pethidine 1 mg/kg + atropine 0.01 mg/kg or with only pethidine 1 mg/kg i.m. Anaesthesia was induced with thiopental. After both types of premedication, either d-tubocurarine 0.5 mg/kg, alcuronium 0.3 mg/kg, pancuronium 0.1 mg/kg, vecuronium 0.1 mg/kg or atracurium 0.5 mg/kg was injected after thiopental. Laryngoscopy was performed 4 min after the relaxant. The control values of the QT intervals (mean value 433 ms, range of the mean values 422-453 ms), were comparable. After thiopental, the mean values in the groups were no longer in the normal range (less than 440 ms). After atropine, the values at 3 min were statistically significantly prolonged in the pancuronium, atracurium and alcuronium groups, but not in the other groups, when compared with the values after thiopental. In the absence of atropine, no statistically significant prolongation of the QT interval occurred. After intubation in the absence of atropine, the values were statistically significantly prolonged in the alcuronium, pancuronium, vecuronium and atracurium groups and in the presence of atropine in the atracurium group when compared with the preceding values. The QT intervals were prolonged only in relation to the increased heart rate. At 6.5 min, the values in all groups were decreased to about the same level as before intubation. The mean control values of the heart rate were between 80 and 90 b.p.m. in the atropine-treated groups and between 70 and 80 b.p.m. in the other groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2905567 TI - Multiple nonfunctional pancreatic islet cell tumor in multiple endocrine neoplasia type I. A case report. AB - A case of multiple nonfunctional pancreatic islet cell tumor in multiple endocrine neoplasia type I (MEN I) is reported. The patient was a 41-year-old woman who had a past history of thyroid cancer (papillary carcinoma) and hyperparathyroidism due to parathyroid adenoma. Later, a nonfunctional pituitary tumor and five nonfunctional pancreatic tumors were found simultaneously and the patient was finally diagnosed as having MEN I. Following surgical enucleation, the pancreatic tumors were histopathologically diagnosed as benign islet cell tumors. One of them (tumor 3) exhibited a solid nodular pattern while the others showed gyriform patterns. They were divided histochemically and immunohistochemically into three types: two (tumors 1 and 2) produced a single hormone (glucagon), one (tumor 3) produced five (insulin, glucagon, somatostatin, gastrin and pancreatic polypeptide) and the remaining two (tumors 4 and 5) produced two (glucagon and pancreatic polypeptide). Electron microscopically, three types of endosecretory granules were found in the tumor cells of tumor 3 but only one type was found in tumor 4. However, in the tumor 4 extract, glucagon, pancreatic polypeptide, C-peptide, somatostatin, vasoactive intestinal peptide and growth hormone releasing factor were detected by radioimmunoassay. These findings suggest that these pancreatic tumors were both multicellular and multihormonal. PMID- 2905568 TI - [The formal total synthesis of securinine]. PMID- 2905569 TI - [Effect of monoamine transmitters on 3-acetylaconitine analgesia]. PMID- 2905570 TI - Synapse formation and development of neurotransmitter functions in neuronal cells from chick brain cultured in a serum-free, defined medium. AB - Cells dissociated from cerebral hemispheres of 8-day-old chick embryos were seeded on poly-L-lysine coated Petri dishes in serum-containing medium. After 24 hr the culture medium was switched to a serum-free, chemically defined medium. These cultures contain mainly neuronal cells until day 14, characterized by the presence of acetylcholinesterase activity and neurofilament proteins. After 2 weeks glial cells progressively contaminated the neuronal culture. Cultures were maintained for a period of 4 weeks. From day 6 on numerous synapses with clear vesicles were observed. The activity of choline acetyltransferase remained low throughout the culture period, while GABA levels increased in parallel with synaptogenesis. Our observations indicate that chick cerebral hemisphere neuronal cultures grown in serum-free, chemically defined medium contain GABAergic neurons that undergo maturation. PMID- 2905571 TI - Neurochemical development of the striatum in a precocial (guinea pig) and an altricial (rat) species. AB - In this study, the developmental patterns of key neurotransmitter marker enzymes, namely choline acetyltransferase (ChAT), glutamate decarboxylase (GAD), and tyrosine hydroxylase (TH) in the corpus striatum were compared between the guinea pig and rat. In an attempt to assess cell acquisition and differentiation, striatal DNA and protein content were also determined during development in the two species. The most outstanding feature apparent from these investigations was a sequential maturation of the three neurotransmitter-synthesizing enzymes: TH and GAD first, followed by ChAT in striata of both species. The developmental increase in DNA content suggests that cell acquisition in the rat striatum is approximately 50% at birth, whereas in the guinea pig, the total population is present before birth, and thereafter cell numbers decline. The accretion of protein, reflecting the increase in region size, continued into adulthood in both species. With emphasis on cholinergic neurons, the neurochemical findings are assessed in relation to the morphological descriptions of cellular changes during pre- and postnatal development of the striatum. PMID- 2905572 TI - Age-dependent beta-adrenergic response of neuronal discharge in the raphe dorsalis: evidence of a transient regulation. AB - Extracellular recordings from raphe dorsalis neurons in rats during development were performed, and the response to iontophoretically applied beta-antagonists was analysed. In pups younger than 2 weeks, raphe dorsalis firing was totally or partially inhibited by application of beta-antagonists, while after 2 weeks of age the neurons were insensitive to the same application. The beta-receptors appeared to be involved in the control of raphe firing during a transient period of ontogenesis and thus the disappearance of beta-regulation at older ages may reflect the regression of this population of neurotransmitter receptors. PMID- 2905573 TI - The effects of transplantation of granulocyte-macrophage progenitors on bone resorption in osteopetrotic rats. AB - Osteopetrosis in the ia (incisors absent) rat is the result of reduced bone resorption due to abnormal osteoclasts. This mutant and others have been used to determine the precursor(s) to osteoclasts. Hemopoietic stem cells, isolated from bone marrow of normal littermates, cure the skeletal sclerosis and result in the formation of normal osteoclasts when transplanted into ia rats. These studies were conducted to define further the precursor to the osteoclast by evaluating the effects of the transplantation of granulocyte-macrophage progenitors on bone resorption in the ia rat. Granulocyte-colony forming cells (G-CFC), granulocyte macrophage-colony forming cells (GM-CFC), and macrophage-colony forming cells (M CFC) were isolated from normal bone marrow using an FITC-labeled monoclonal antibody directed against rat Thy-1.1 and fluorescence-activated cell sorting. The isolates were evaluated in soft agar culture; granulocyte isolates generated 71% G-CFC of all colonies formed and were enhanced 27 times over unfractionated cells. Mixed isolates generated 57% GM-CFC of all colonies formed and were 15 times enhanced, while macrophage isolates were 75% M-CFC with an enhancement factor of 18. The isolated populations were injected into 3-week-old ia recipients and evaluated for the ability of these cellular isolates to correct the bone resorption defect by measuring the size of the tibial marrow cavity and by identifying morphologically normal osteoclasts. In addition, isolated populations of cells were labeled with FITC and injected into ia donors to determine if labeled osteoclasts developed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2905574 TI - The evolution of the World Federation of Neurosurgical Societies. AB - To summarize this report, it seems that the neurosurgical family has grown up. The children have gone their several ways to elaborate upon the teachings of their mentors and the old folks are being put on the shelf out of the way of the hustling young nut crackers anxious to get to the operating room. If you doubt this conclusion, note that at the Toronto Congress, only 4 of the 37 officers- the old guard--were listed to present papers on the scientific program. One wonders if the experience and wisdom of the older members is not being lost. Is there not a place on the broadening program for invited presentations by senior members? Finally to those who have so unselfishly given of their services to lighten my task in the past dozen years, I extend my thanks and gratitude. To those members, credit is due for any service which the historian may have been able to render to the World Federation of Neurosurgical Societies. PMID- 2905575 TI - Intracellular recordings from neurones in rat cerebral cortex during hypoxia. AB - Neurones in rat hippocampal cortex were exposed to hypoxia while their membrane properties and responses to different kinds of stimuli were recorded with an intracellular electrode. The initial changes consisted of a small depolarization followed by a hyperpolarization. Following these early events the neurones lost their membrane potential through a large depolarization. Similar changes were observed in neurones where the Na/K-ATPase was blocked by ouabain. Responses to direct application of the transmitters GABA and glutamate, which was lost at this point, were restored by passive reestablishment of the membrane potential with current through the intracellular electrode. PMID- 2905576 TI - [The unstable elbow joint following dislocation. Diagnosis and therapy]. AB - The meaning of instability after elbow dislocation (unstable dislocation) is pointed out. We support the trend to surgical treatment in cases of obvious instability and emphasize a differentiated concept in diagnosis and therapy. 32 patients after elbow dislocation were treated and followed up after an average period of 7.5 months. Good to very good results could be achieved in 24/32 patients (75%). PMID- 2905577 TI - [Costoclavicular syndrome--a rare complication of clavicular fracture]. AB - Neurological or vascular complications in clavicle fractures as a primary lesion are rare. More often these complications develop later caused by large callus formation to encroach the costoclavicular space. That is due sometimes to an additional fracture of the clavicle, which healed under shortening. The prognosis of the costoclavicular syndrome can be improved by early resection of the callus formation and--in special cases--by reconstruction of the original length of the clavicle combined with a stable plate osteosynthesis. PMID- 2905578 TI - [Talus necrosis and its treatment]. AB - Aetiopathogenesis of the necrosis of the talus has not yet been definitely clarified, and neither has that of the other aseptic necroses. We were able to study the aetiopathogenesis, course of the disease and therapy in 20 of our own patients by follow-up; two of these developed necrosis of the talus in both feet. We definitely excluded patients suffering from osteochondrosis dissecans. Even though fracture of the talus is on the whole relatively rare, it remains the most frequent cause of necrosis of the talus. We also found talonecrosis after surgical correction of clubfoot, after Sudeck's disease (Sudeck-Leriche syndrome, Sudeck's atrophy or dystrophy), suppurative arthritis of the ankle joint, subtalar luxation and haematogenic osteomyelitis. Only few patients required surgery. In most cases a special boot constructed for arthrodesis patients proved sufficient. Each patient developed arthrodesis to a different degree. Depending upon the complaints and stiffening of the ankle joint or of the talo calcanonavicular joint, the capacity of the patients to be gainfully employed was reduced by an amount between 20 and 30 per cent. PMID- 2905579 TI - [Therapy of joint infections]. AB - The therapy of septic arthritis should lead to control of infection and a good joint function as well. So it is necessary to combine the classic methods (revision, immobilisation, antibiotic therapy) with functional treatment. The possibilities, aims and limits of early CPM or replacement of an infected prosthesis (in one or two steps) are discussed. PMID- 2905580 TI - [Arthrotomy--a prearthrotic factor?]. AB - Light-microscopic and electron microscopic findings of the synovial membrane and cartilage were compared, of rabbit knee joints on which arthrotomy and surgical induced instabilisation operation were performed. The joint opening was followed by an inflammation of the synovial membrane, and cartilage changes were similar in joints of arthrotomy and surgically induced instability. CLINICAL RELEVANCE: To prevent joints from further damage after arthrotomy or arthroscopy, joints should be spared from weight bearing during the time of synovial inflammation. PMID- 2905581 TI - [Pediatric traumatic hip joint dislocation--overview of the topic based on 9 personal, previously unpublished cases]. AB - We report on 8 patients with 9 traumatic hip dislocations in childhood. The follow-up period was between 1 and 21 years. The majority of these rare injuries were caused by major, sometimes, however, by minor trauma. The best prognosis is given by an immediately performed closed reduction in the absence of bony injuries. Five of our patients had associated bony injuries (fractures of the femoral shaft, acetabular fractures). Two of our patients developed an avascular necrosis of the femoral head which needed further surgery; in one case we found a premature closure of the proximal femoral epiphyseal plate, a fourth patient developed premature osteoarthritis due to a concomitant acetabular fracture. Clinical and radiological examination of all other patients showed no residues of the former injury. PMID- 2905582 TI - [Treatment of femur shaft fractures in children with Ender nails]. AB - Ender-nailing is a proved method in the treatment of sub- and pertrochanteric fractures in old people. In special cases Ender-nailing can be useful in the treatment of other types of fractures. 3 cases of Ender-nailing of femoral shaft fractures in childhood are reported. PMID- 2905583 TI - [Plastic reconstruction of the acetabulum with a form-matching spongiosa transplant]. PMID- 2905584 TI - Gain regulation of the vestibulospinal reflex following microinjection of a beta adrenergic agonist or antagonist into the locus coeruleus and the dorsal pontine reticular formation. PMID- 2905585 TI - Mammalian macular organization: a model information network. PMID- 2905586 TI - [Possible mechanism of the ocular hypotensive effect of clonidine in the pigmented eye rabbit]. PMID- 2905588 TI - [Clinical experiences with alfentanil for balanced anesthesia in upper abdominal surgery]. AB - METHODS: Three randomized groups of patients scheduled for upper abdominal surgery received either an initial large bolus of alfentanil combined with low concentrations of isoflurane (group 1), an initial small bolus of alfentanil combined with 50% higher isoflurane concentrations than group 1 (group 2), or isoflurane without opioids (group 3). Blood pressure, heart rates, and anesthetic consumptions were measured and recorded, as were side-effects such as thoracic rigidity, bradycardia, and nausea, and postoperative recovery time. RESULTS: The mean isoflurane concentration in group 1 was 0.8 vol% combined with an average alfentanil bolus of 6.8 mg and three additional doses of 1.1-1.4 mg. Group 2 received a mean isoflurane concentration of 1.3 vol% combined with four additional doses of 1.3-1.7 mg alfentanil. Group 3 needed an average isoflurane concentration of 1.5 vol%. Side effects of alfentanil were prevented by atropine administration; severe complications were not observed. Postoperative recovery time showed significant differences between groups 1 und 2: group 1 patients were awake within 7.5 min and group 2 within 17 min after the operation. No respiratory depression was detected. CONCLUSIONS: Alfentanil combined with volatile anesthetics produced no severe side-effects in patients scheduled for upper abdominal operations. The pharmacokinetics of alfentanil are advantageous with regard to the postoperative period. PMID- 2905587 TI - Alterations in cholinergic muscarinic and somatostatin binding sites in a patient with idiopathic intestinal pseudo-obstruction. AB - We present a comparative study of cholinergic muscarinic and somatostatin binding sites on isolated membranes from mucosa and tunica muscularis of normal and dilated parts of the proximal jejunum obtained at surgery from a patient with idiopathic intestinal pseudo-obstruction (IIP) syndrome. We found a statistically significant diminution of cholinergic muscarinic and somatostatin binding sites in mucosa taken from the dilated part of the jejunum, compared with those taken from the normal part. Tunica muscularis of the dilated part of the jejunum contained a significantly higher concentration of peripheral cholinergic muscarinic binding sites (M2) than the normal part did, whereas concentration of M1 cholinergic muscarinic and somatostatin binding sites was similar in both examined parts. These results indicate that IIP-syndrome may be related to alterations in cholinergic muscarinic binding sites in the tunica muscularis of the intestine. PMID- 2905589 TI - [The effect of neuroleptics and neuroleptic/analgesic combinations on the sensitivity to seizures in mice]. AB - Combinations of neuroleptic and morphine-like analgesic drugs are used alone for minor surgery or as anesthetic premedication. While morphine-like analgesics given in the therapeutic dose range show anticonvulsant properties, there is evidence indicating that neuroleptics are rather proconvulsant. This study was performed to investigate the influence of the most widely used combinations pethidine/promethazine and fentanyl/droperidol on seizure susceptibility. METHODS: Thresholds for convulsions induced by electroshock and pentetrazole infusion were used as models for seizure susceptibility. The drugs tested were injected s.c. 20-30 min before determination of the seizure threshold. RESULTS: Pethidine/promethazine and fentanyl/droperidol reduced the susceptibility to seizures induced by electroshock. Promethazine and droperidol alone elevated the threshold only at the highest doses used (2 mg/kg and 2.5 mg/kg respectively). Promethazine, whether given alone or in combination with pethidine, showed no effect on the threshold for pentetrazole-induced convulsions. Droperidol alone lowered the threshold for pentetrazole-induced clonic convulsions only at the lowest dose used (0.625 mg/kg), but lowered that for tonic convulsions at all doses studied (0.625, 1.25 and 2.5 mg/kg). The combination of fentanyl and droperidol lowered the threshold for both clonic and tonic convulsions at the two lower doses (12.5 micrograms/kg fentanyl + 0.625 mg/kg droperidol and 25 micrograms/kg fentanyl + 1.25 mg/kg droperidol). Only the highest dose studied (50 micrograms/kg fentanyl + 2.5 mg/kg droperidol) showed no significant effect. CONCLUSION: Pethidine and fentanyl show anticonvulsant properties in mice, but it is evident from our results that there is some interaction between their combinations with neuroleptics and seizure susceptibility. This is more pronounced with the combination fentanyl/droperidol in the model of pentetrazole induced convulsions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2905590 TI - [Benefits and risks of H2 antagonists in anesthesia and intensive medicine]. PMID- 2905591 TI - AIDS 1988. The science and the limits of science. PMID- 2905592 TI - [Synthesis and anti-allergic properties of N-arylnitrones with furo-pyran structure]. PMID- 2905593 TI - [Sequential mammary graft: indications, operative technic, functional and angiographic control at 6 months. Apropos of 170 patients]. PMID- 2905594 TI - Changes in the activities of various lipid and carbohydrate biosynthetic enzymes in the diatom Cyclotella cryptica in response to silicon deficiency. AB - The effects of silicon deficiency on the activities of several enzymes involved in lipid and storage carbohydrate synthesis in the diatom Cyclotella cryptica were determined. The activity of UDPglucose pyrophosphorylase was not affected after 4 h of silicon-deficient growth, but the activity of UDPglucose: beta-(1--- 3)-glucan-beta-3-glucosyltransferase (chrysolaminarin synthase) was reduced by 31% during this period. Acetyl-CoA synthetase, acetyl-CoA hydrolase, and citrate synthase activities were present in cell-free extracts of C. cryptica, but did not change in response to 4 h of silicon deficiency. However, the activity of acetyl-CoA carboxylase increased approximately two- and fourfold after 4 and 15 h of silicon-deficient growth, respectively. This induction could be blocked by cycloheximide (20 micrograms/ml) and actinomycin D (10 micrograms/ml), suggesting that silicon deficiency may induce an increase in the rate of acetyl-CoA carboxylase synthesis. These changes in enzymatic activity may be partially responsible for the accumulation of lipids that has been observed in C. cryptica and other diatoms in response to silicon deficiency. PMID- 2905595 TI - Effects of ethanol feeding on hepatic lipid synthesis. AB - Rats were fed a high-fat, liquid diet containing either 36% of total calories as ethanol or an isocaloric amount of sucrose, for a period up to 35 days. At different time intervals we measured the effects of ethanol administration on the activities of a number of key enzymes involved in hepatic lipid synthesis. At the start of the experimental period the activities of acetyl-CoA carboxylase and fatty acid synthase, measured in liver homogenates, increased in the control as well as in the ethanol-fed group. After 35 days these enzyme activities were still elevated but there were no significant differences between the two groups. In hepatocytes isolated from controls as well as from ethanol-fed rats, short term incubations with ethanol induced an increase in the rate of fatty acid synthesis and in the activities of acetyl-CoA carboxylase and fatty acid synthase. However, no alterations in the regulation of these enzymes by short term modulators of lipogenesis were apparent in hepatocytes isolated from alcohol treated animals. The results do not indicate a major role for the enzymes of de novo fatty acid synthesis in the development of the alcoholic fatty liver. The amount of liver triacylglycerols increased in ethanol-fed rats during the entire treatment period, whereas the hepatic levels of phosphatidylcholine and phosphatidylethanolamine were not affected by ethanol ingestion. Ethanol administration for less than 2 weeks increased the activities of phosphatidate phosphohydrolase, diacylglycerol acyltransferase, and microsomal phosphocholine cytidylyltransferase, whereas the cytosolic activity of phosphocholine cytidylyltransferase was slightly decreased. Upon prolonged ethanol administration the activities of these enzymes were slowly restored to control values after 35 days, suggesting development of some kind of adaptation. It is interesting that, although the activities of phosphatidate phosphohydrolase and diacylglycerol acyltransferase were restored to the levels found in the control rats, this effect was not accompanied by a stabilization or decrease of the concentration of hepatic triacylglycerols. PMID- 2905596 TI - Role of maternal antibody in protection from hemorrhagic fever with renal syndrome virus infection in rats. AB - The effect of maternal antibody on the protection of newborn rats from infection of HFRS virus strain SR-11 was examined. Antibody to HFRS virus was transferred from immune dams to their offspring prenatally as well as postnatally. IgG antibody was detected in the sera of fetuses by IFA test (titers from 1:64 to 1:256) and in fetal fluids (1:32) obtained from the uteri of immune dams at 20 days after mating. In the sera of the newborn, IgG titers of maternal antibody ranged from 1:64 to 1:256 just after birth, reached a peak titer around 1:2,048 at 2 weeks after birth, then declined and disappeared at about 8 weeks of age. No IgA and IgM antibodies were detected in the sera of fetuses and newborns. After intraperitoneal challenge by strain SR-11 (10(2.2) LD50), death and infection of 2-day-old rats from immune dams were prevented by the presence of maternal antibody. The protective effect of maternal antibody remained in 8-week-old rats having an IFA titer of maternal antibody as low as 1:16, and even in some 10-week old rats with negative tests for maternal antibody. PMID- 2905597 TI - [The structures in the immunological circuits--the role of CD4+ T cells]. PMID- 2905598 TI - Structural interpretation of the binding of 9-azidoacridine to D-amino acid oxidase. AB - D-Amino acid oxidase (EC 1.4.3.3) forms an inhibited complex with the nucleotide- and aromatic-binding-site affinity reagent 9-azido[3H]acridine. Tryptic digestion of the photolysed complex yielded two radioactive peptides, 222-265 (T23) and 298 328 (T29), which core and secondary structure analysis revealed to be exposed, but which also comprised the propargylglycine-binding residues. This suggests that at least parts of the peptides containing these residues are in the active centre and that they are spatially close to the flavin-binding site. PMID- 2905599 TI - Stereoselective blockade of alpha-adrenoceptors by berbine derivatives. AB - The effects of the two enantiomers of berbine (5,6,13,13a-tetrahydro-8H dibenzo[a,g]quinolizine) and of derivatives obtained by introducing various substitutions on aromatic rings were investigated on alpha 1- or alpha 2 adrenoceptor subtypes. Binding studies carried out on rat cerebral cortex membranes using [3H]prazosin or [3H]yohimbine showed that the affinities of the (+) and (-)enantiomers for alpha 1 and alpha 2 binding sites were different and were differently modified by substitutions added to the berbine nucleus, leading to alpha 1- and alpha 2-selective compounds. Experiments performed on the isolated rat aorta and in pithed rats in vivo demonstrated the alpha-blocking property of berbine derivatives and confirmed the stereoselectivity of the effects of the (+) and (-)enantiomers on alpha 1- and alpha 2-adrenoceptor subtypes. PMID- 2905600 TI - A study of DNA polymorphism in the apolipoprotein B gene in a Japanese population. AB - A Japanese group comprising 53 hyperlipidemic and 54 normolipidemic subjects was genotyped for DNA restriction fragment length polymorphisms (RFLPs) at the apo B gene locus. The polymorphisms with XbaI and PvuII were present at allelic frequencies of 0.04 (X1 allele) and 0.96 (X2 allele), 0.94 (P1 allele) and 0.06 (P2 allele), respectively. Unlike the previous reported association of the X1 allele with hypercholesterolemia found in Caucasians there was no difference in the frequency of the X1 allele between normolipidemic and hypercholesterolemic Japanese. Among the Japanese, two RFLPs appear to be in linkage equilibrium and can be used in conjunction as a haplotype. There is no strong population association in our patient group between any allele of the RFLPs studied and hyperlipidemia. PMID- 2905601 TI - XbaI and c/g polymorphisms of the apolipoprotein B gene locus are associated with serum cholesterol and LDL-cholesterol levels in Finland. AB - Several restriction fragment length polymorphisms (RFLPs) have been identified within or adjacent to the gene locus for apolipoprotein B (apo B), the major protein component of serum low density lipoprotein (LDL). One of these, detected with the restriction enzyme XbaI, has been suggested to be involved in the determination of serum lipid levels in some but not all populations. We determined the XbaI genotypes and serum lipoprotein levels of 176 apparently healthy unrelated Finns. Subjects homozygous (genotype X2X2) or heterozygous (genotype X1X2) for the presence of the XbaI restriction site within the apolipoprotein B gene (n = 113) had, on the average, an 11% higher serum total cholesterol (P = 0.01) level than those homozygous for the absence of this site (genotype X1X1, n = 63). In addition, the X2 allele was significantly associated with apo B(c), another allele reportedly associated with elevated serum cholesterol levels. The combined genotype (both X2 and apo B(c) alleles present) resulted in a greater elevation of total cholesterol (P = 0.004, when compared to subjects with neither allele) and LDL-cholesterol (P = 0.02) than the presence of either allele alone. The results suggest that both the XbaI and apo B(c/g) sites are in linkage disequilibrium with a functionally important DNA alteration within or adjacent to the apo B gene but the XbaI locus may be in stronger linkage disequilibrium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2905602 TI - [Hyperplasia of antral "G" cells. Quantitative evaluation in endoscopic biopsies]. AB - The number of gastrin cells (G cells) and somatostatin cells (D cells) per surface unit, and the G/D cell ratio were estimated in biopsy specimens of the antrum from normal subjects without hypergastrinemia, and from patients with hypergastrinemia not induced by gastrinoma or supra selective vagotomy. Compared with normal subjects, antral G cell density and G/D cell ratio were significantly increased in patients with hypergastrinemia. A significant correlation was found between G cell density or G/D cell ratio and the integrated gastrin output values. A quantitative estimation appears therefore possible in biopsy specimens. PMID- 2905603 TI - [Bibliographic review of antihistaminics H2 in the treatment of chronic (or recurrent) idiopathic urticaria]. AB - Cimetidine alone has not been shown conclusively to be effective in the treatment of urticaria. Cimetidine in combination with an H1 antihistamine has been shown to be effective in studies of patients who could not be controlled by H1 antihistamine alone. In that section of the patient population with "untreatable" chronic urticaria, the use of an H2 antagonist in conjunction with an H1 antagonist should be considered as a possible treatment. PMID- 2905604 TI - Biosynthesis of the cancer-associated sialyl-Lex determinant in human amniotic fluid. AB - Biosynthesis of the sialyl-Lex determinant (NeuAc alpha 2-3Gal beta 1-4(Fuc alpha 1-3)-GlcNAc beta 1-3-R) in human amniotic fluid has been shown to proceed via the same sequence of glycosylation steps established previously for lung carcinoma PC 9 cells (Holmes, E. H., Ostrander, G.K. & Hakomori, S. (1986) J. Biol. Chem. 261, 3737-3743): sialylation of type-2-chain-precursor substrates (paragloboside) by an amniotic alpha 2-3-sialyltransferase precedes fucosylation of sialylated intermediates (sialosyl paragloboside) by an organ-characteristic alpha 1-3-L fucosyltransferase. PMID- 2905605 TI - Antihypertensive drugs and lipid profiles. AB - The large clinical trials of the treatment of hypertension, in which diuretics were used as initial drug therapy, have demonstrated a major reduction in stroke but little benefit in the incidence of coronary heart disease. The limited effect of treatment on coronary disease is surprising given the strong risk factor relationship to pre-existing hypertension. This may mean that the risk factor relationship is not a causal one. Alternatively, the drug therapy may have subtle toxicity that in the long term offsets the benefit of lowering blood pressure. This review explores the latter possibility by reviewing the evidence that the antihypertensive drugs used preferentially heretofore have adverse effects on the lipid profile. Diuretics increase triglycerides (average of 30%), total cholesterol (average of 6-8%), and LDL or VLDL cholesterol. beta-1 selective and nonselective beta-blockers increase triglycerides (average of 30%) and lower HDL cholesterol (average of 5-15%). Whereas the adverse modifications of the lipid profile appear small and inconsequential, the increase in total cholesterol during diuretic therapy is of the same magnitude as observed in the Lipid Research Clinic trial (although opposite in direction) that significantly affected coronary events. The persistence of the lipid changes during long-term treatment is unresolved due to fragmentary and poorly controlled observations. Nevertheless, considerable data suggest that it continues during extended therapy. Selective alpha-1 adrenoceptor blocking drugs and perhaps calcium antagonists and beta-blockers with intrinsic sympathomimetic activity have a favorable influence on the lipid profile.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2905606 TI - Critical comments on recent literature. SCRAAPHY about MAPHY from HAPPHY. PMID- 2905607 TI - Properties of European eel (Anguilla anguilla) liver cell sap acetyl-CoA carboxylase. PMID- 2905608 TI - Regulation of eel (Anguilla anguilla) liver acetyl-CoA carboxylase by changes in the polymeric state of the enzyme. PMID- 2905609 TI - A negative human serosurvey of haemorrhagic fever viruses in Djibouti. PMID- 2905610 TI - Interaction of HIV infection with nervous tissue may play a crucial role in the development of AIDS. AB - In this note, we first review some of the immunopathogenic mechanisms of HIV infection and discuss the possible role of the idiotypic network in producing immunodeficiency; we then propose that the interaction of HIV with the nervous system is such as to generate signals which are misinterpreted by the nervous system: the feedback reaction of the nervous system may play a crucial role in the development of AIDS. We conclude by studying a very simple model for the dynamics of AIDS. PMID- 2905611 TI - 'Dental sedation'. PMID- 2905612 TI - A survey of hypokalaemia in patients of general practitioners. PMID- 2905613 TI - The kinetics of immunologic and hematologic recovery in mice after lethal total body irradiation and reconstitution with syngeneic bone marrow cells treated or untreated with mafosfamide (ASTA Z 7654). AB - The immunohematopoietic reconstitution of mice lethally irradiated (TBI) and reconstituted with syngeneic bone marrow cells untreated or treated with mafosfamide (ASTA Z 7654) [TBI + SBMT or TBI + SBMT-Maf mice, respectively] was examined. The number of CFU-S was greatly reduced in TBI + SBMT-Maf mice compared with those in TBI + SBMT mice. The recovery of blood parameters (hematocrit, reticulocytes, erythrocytes, white blood cells, granulocytes, platelets) and of bone marrow and spleen cells, but not of peritoneal exudate cells, was slightly delayed in TBI + SBMT-Maf mice compared with those in TBI + SBMT mice. The time for immune system regeneration was, however, considerably longer in TBI + SBMT Maf than in TBI + SBMT mice, as measured by the incidence of Ig+, Thy-1.2+, L3T4+, Lyt-2+, and IL-2R+ cells in the spleens. The appearance of Mac-1+ and asialo-GM 1+ cells was only slightly prolonged or unchanged, respectively. PMID- 2905614 TI - Autologous bone marrow transplantation in patients with non-Hodgkin's lymphoma: comparison of different parameters in predicting the kinetics of haematological recovery. AB - We analysed the kinetics of haematological recovery after autologous bone marrow transplantation (ABMT) in 31 patients with non-Hodgkin's lymphoma, of whom 14 had received chemotherapy and 17 had received no chemotherapy before marrow harvesting. The time for recovery of polymorph (PMN) and platelet numbers was assessed in relation to patient's sex, age, the numbers of mononuclear cells (MNC) and of granulocyte-macrophage colony-forming cells (CFU-GM) reinfused, the therapy before harvesting and the conditioning regimens. The results showed that the most important factor influencing the speed of haematological recovery was therapy before marrow collection; recovery was faster in patients not treated before harvesting than in those treated. The mean day for PMN recovery to 0.5 x 10(9)/l was 14.6 vs 21.8 (p less than 0.001); the mean day for platelet recovery to 50 x 10(9)/l was 16.5 vs 44.4 (p less than 0.00002). The other parameters assessed did not correlate with the kinetics of haemopoietic recovery. We conclude that NHL patients who undergo ABMT without chemotherapy prior to marrow harvest have rapid haematological recovery, which suggests that better timing of the harvest could be of value in the management of NHL patients for whom 'reinforcement' with ABMT is scheduled. PMID- 2905615 TI - Modality-specific antinociception produced by intrathecal injection of anti somatostatin antiserum in rats. AB - An intrathecal injection of antiserum against somatostatin significantly inhibited the nociceptive response to thermal but not mechanical stimulation in non-arthritic and adjuvant arthritic rats. The thermal antinociception induced by intrathecally injected anti-somatostatin antiserum was more remarkable in adjuvant arthritic rats than in non-arthritic ones. These results suggest that endogenous somatostatin participates in transmission of thermal nociception in the rat spinal dorsal horn in non-arthritic and arthritic conditions. PMID- 2905616 TI - Antagonism of spontaneous and evoked bursts by 6-cyano-7-nitroquinoxaline-2,3 dione (CNQX) in the CA3 region of the in vitro hippocampus. AB - Superfusion of hippocampal slices with 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) antagonized kainate-induced bursts and bursts of unknown origin in the CA3 region. CNQX also increased the latency of and eventually blocked evoked bursts which persist following kainate washout. In contrast, D-(-)-2-amino-7 phosphonoheptanoic acid did not alter burst latency or block bursts unless applied subsequent to CNQX. We conclude that the quisqualate type receptor has a prominent role in burst generation with a smaller contribution from N-methyl-D aspartate receptors. PMID- 2905617 TI - Met5-enkephalin-Arg6-Gly7-Leu8 immunoreactivity in rat and human cerebrospinal fluid: influence of neuroleptic drugs and electroconvulsive shock. AB - Met5-Enkephalin-Arg6-Gly7-Leu8 immunoreactivity was quantitated in both rat and human cerebrospinal fluid (CSF) by radioimmunoassay with a carboxy-terminal directed antiserum. The immunoreactivity in CSF was chromatographically characterized in both species and was found to consist almost exclusively of high molecular weight forms. In human CSF there was approximately 300 fmol/ml and in the rat 1,500 fmol/ml of immunoreactivity. The possibility of a rostro-caudal gradient was examined in the human by analyzing the first and the twenty-fifth ml of CSF drawn during a lumbar puncture: none was found. The immunoreactivity was fairly stable; no loss of immunoreactivity was observed after 24 h of incubation of rat CSF at 37 degrees C. Electroconvulsive shock (ECS) produced a significant elevation in CSF content but only after a course of chronic administration; a single acute ECS produced no increase. Human subjects with schizophrenia who were being treated with antipsychotic drugs had elevated levels of immunoreactivity in comparison to non-mediated patients and normals. The high levels of this immunoreactivity in CSF, its stability and the evidence that the content can change with physiological and pharmacological manipulation indicate that Met5 Enkephalin-Arg6-Gly7-Leu8 immunoreactivity can serve as a new and useful CSF marker for investigating the CNS enkephalin system in neurological or psychiatric disorders. PMID- 2905618 TI - Calcium-dependent release of N-acetylaspartylglutamate from retinal neurons upon depolarization. AB - N-Acetylaspartylglutamate (NAAG) is present in high concentrations specifically in the nervous system. Its neuronal distribution, presence in synaptic vesicles and its excitatory actions support the hypothesis that this dipeptide participates in communication between neurons. Following the incorporation of [3H]glutamate by frog retinal cells in vivo, the release of radiolabeled glutamate, GABA and NAAG was studied during acute incubation of the retina in vitro. Release of the radiolabeled amino acids and dipeptide was stimulated by elevated extracellular potassium. The release required the presence of extracellular calcium. These data are the first which demonstrate the release of NAAG following biosynthesis from a radiolabeled precursor and are consistent with synaptic release of this dipeptide. PMID- 2905619 TI - A monoclonal antibody to a parasympathetic neurotrophic factor causes immunoparasympathectomy in mice. AB - A monoclonal antibody capable of blocking the biological activity of the ciliary neurotrophic factor purified from bovine cardiac muscle has been produced. This antibody, when administered perinatally to mice, causes a failure of the normal development of the parasympathetic innervation of the iris as determined by assay for the activity of the cholinergic marker enzyme choline acetyltransferase. The same treatment has no effect on the adrenergic neuronal marker, tyrosine hydroxylase. This immunoparasympathectomy suggests that the ciliary neurotrophic factor has an essential role in regulating the development of the mammalian parasympathetic nervous system. PMID- 2905621 TI - Isolation of pyroGlu-Leu-Leu-Gly-Gly-Arg-Phe-NH2 (Pol-RFamide), a novel neuropeptide from hydromedusae. AB - The hydromedusa Polyorchis penicillatus is a good model system to study neurotransmission in coelenterates. Using a radioimmunoassay for the peptide sequence Arg-Phe-NH2 (RFamide), two peptides have now been purified from acetic acid extracts of this medusa. The structure of one of these peptides was established as pyroGlu-Leu-Leu-Gly-Gly-Arg-Phe-NH2, and was named Pol-RFamide. This peptide belongs to the same peptide family as a recently isolated neuropeptide from sea anemones (pyroGlu-Gly-Arg-Phe-NH2). Using antisera to Pol RFamide, the peptide was found to be exclusively localized in neurones of Polyorchis, among them neurones associated with smooth-muscle fibres. This suggests that Pol-RFamide might be a transmitter or modulator at neuromuscular junctions. PMID- 2905620 TI - Demonstration of calcitonin gene-related peptide immunoreactive axons contacting dynorphin A(1-8) immunoreactive spinal neurons in a rat model of peripheral inflammation and hyperalgesia. AB - In a rat model of peripheral inflammation and hyperalgesia, dynorphin A(1-8)-like immunoreactive (DYN-LIr) spinal neurons were examined for contacts from calcitonin gene-related peptide-like immunoreactive (CGRP-LIr) varicosities using a double-label PAP method. Ipsilateral to the inflammation, CGRP-LIr varicosities contacted both dendrites and somata of DYN-LIr neurons in lumbar laminae I, II and V. Few such contacts were found on the contralateral side. The results suggest that opioid neurons which exhibit a dynamic change in dynorphin associated with inflammation, represent a subpopulation of neurons that receive contacts from presumptive nociceptive primary afferents. PMID- 2905622 TI - Electrophysiological characterization of adrenoceptors in the rat dorsal hippocampus. I. Receptors mediating the effect of microiontophoretically applied norepinephrine. AB - The rat hippocampus receives a dense noradrenergic innervation originating exclusively from the locus coeruleus. The present electrophysiological study was undertaken to characterize the adrenoceptor mediating the suppressant effect of microiontophoretically applied norepinephrine (NE) on CA1 and CA3 dorsal hippocampus pyramidal neurons of the rat. The rank order of potency of microiontophoretically applied agonists, in suppressing the firing rate of hippocampus pyramidal neurons was: oxymetazoline greater than NE greater than phenylephrine greater than isoproterenol greater than clonidine. In the hippocampus, oxymetazoline was more potent than NE, whereas it was ineffective in the lateral geniculate nucleus where the effect of NE is mediated by an alpha 1 adrenoceptor. Low currents of clonidine antagonized the effect of NE suggesting that clonidine may exert a partial agonistic effect. The rank order of potency of i.v. administered adrenergic antagonists in blocking the suppressant effect of microiontophoretically applied NE was: idazoxan much greater than prazosin much greater than propranolol. Idazoxan also blocked the effect of oxymetazoline, phenylephrine, and isoproterenol but did not modify the effect of microiontophoretically applied gamma-aminobutyric acid (GABA). In addition, idazoxan, applied by microiontophoresis, readily blocked the suppressant effect of NE without affecting that of GABA. These results suggest that the suppressant effect of microiontophoretically applied NE on rat dorsal hippocampus pyramidal neurons is primarily mediated by alpha 2-adrenoceptors. PMID- 2905623 TI - Locally applied estrogens potentiate glutamate-evoked excitation of cerebellar Purkinje cells. AB - Ongoing studies in our laboratory have demonstrated that systemically administered sex steroids 17 beta-estradiol (E2) and progesterone (P) alter cerebellar Purkinje cell responses to the amino acid neurotransmitter glutamate (Glu) in the urethane-anesthetized, ovariectomized adult rat. In the present study, we have examined the effects of locally pressure ejected E2 (0.5 microM) on Purkinje cell responsiveness to microiontophoretically applied Glu. The inactive stereoisomer of E2, 17 alpha-E2 (0.5 microM), estradiol benzoate (EB, 0.5 microM), and estrone (E1, 0.5 microM) were also tested (vehicle: 0.01% propylene glycol-saline, pH 7.4). Extracellular activity of single Purkinje neurons was recorded using multibarrel glass micropipets. Spontaneous firing rate and neuronal responses to microiontophoretic pulses (10 s every 40 s at 10-50 nA) of Glu were examined before, during and after continuous local pressure application of the steroids (1-5 psi, 10-15 min). Local E2 administration increased Glu response by 86% within 2-3 min after the onset of steroid application, with no recovery apparent by 30 min after termination of steroid administration. As such, local E2 application mimicked the effect of systemic injection of this steroid. The inactive estrogen isomer, 17 alpha-E2, failed to significantly enhance Glu responsiveness. Both EB and E1, however, significantly potentiated Glu responsiveness in a manner similar to locally applied E2. In addition, EB administration produced long-lasting increases in background discharge, unlike E2, and eventual recovery of Glu responses to control pre steroid levels. In summary, this study provides a demonstration of local sex steroid actions on neuronal responsiveness in a model extrahypothalamic CNS area. These effects were specific, as the inactive 17 alpha-E2 isomer did not alter neuronal physiology. The results presented here suggest that the neuronal effects of systemic estrogen may be mediated by local actions of E2 or E1. PMID- 2905625 TI - Neurotransmitter abnormalities in Borna disease. AB - Borna disease (BD) agent is an infectious pathogen that causes progressive central nervous system (CNS) dysfunction in a wide range of vertebrate hosts. The course of BD in adult rats is biphasic. The acute phase is characterized by aggressive behavior and inflammatory cell infiltrates in brain. With chronic infection animals become listless and inflammation resolves. BD antigens are similarly distributed in neurons in hippocampus, neocortex, cerebellum and brainstem in acutely and chronically infected animals. We have recently examined brain levels of neuronal transcripts in rats with acute and chronic BD. Levels for 3 of these mRNAs, cholecystokinin, glutamic acid decarboxylase and somatostatin, were decreased in acutely infected rats and increased toward control values in chronically infected rats. A fourth transcript, MuBr8, correlated in distribution with BD antigen, was persistently decreased throughout the course of infection. These data may have implications for understanding the pathogenesis of neurologic disturbances in BD and other inflammatory CNS diseases. PMID- 2905624 TI - Quisqualate, kainate and NMDA can initiate spreading depression in the turtle cerebellum. AB - This study evaluated the role of excitatory amino acid (EAA) receptor activation in spreading depression (SD), using the in vitro turtle cerebellum as a model system. SD was triggered by electrical stimulation or by elevated K+ after the cerebellum had been conditioned for at least 30 min with physiological saline in which most of the chloride had been replaced by propionate. SD was recognized as a transient (1-3 min) negative shift of extracellular potential accompanied by depression of evoked potentials (15-30 min) and an increase of extracellular K+ up to 60 mM, which spread across the cerebellum at rates of 1-7 mm/min. SD usually commenced in the granular layer, which apparently contains the 3 major EAA receptor subtypes, quisqualate, kainate and N-methyl-D-aspartate (NMDA), then subsequently spread to the molecular layer, which is largely free of NMDA receptors. Glutamate, aspartate, NMDA, kainate and quisqualate all triggered SD. Kynurenic acid and 2-aminophosphonovaleric acid (APV) inhibited SD under certain conditions further suggesting involvement of EAA receptors. The initiation of SD was blocked by high Mg2+ and facilitated in low extracellular Mg2+, which also eliminated the delay in molecular layer SD onset. Our data suggest that no one EAA receptor subtype is singly responsible for SD. PMID- 2905626 TI - Enhancement of dopamine metabolism in rat brain frontal cortex: a common effect of chronically administered antipsychotic drugs. AB - Administration of 4 antipsychotic drugs, haloperidol, chlorpromazine, thioridazine and clozapine, for 21 days elicited increased dopamine metabolism in frontal cortex of rat brain. Only clozapine failed to decrease the apparent firing rate of dopamine neurons in the striatum, as indexed by [homovanillic acid]/[dopamine]. These data support the hypotheses that frontal cortex dopamine neurons may be a common site for antipsychotic action while decreased release of dopamine in the striatum may be associated with the development of extrapyramidal side effects. PMID- 2905627 TI - Glutamate and dynorphin release from a subcellular fraction enriched in hippocampal mossy fiber synaptosomes. AB - A procedure is described for the isolation of intact hippocampal mossy fiber synaptosomes. Electron microscopic examination revealed numerous synaptosomal profiles which are clearly of mossy fiber origin, indicated by their large size (2-6 micron diameter) and characteristic morphology. Furthermore, this fraction is enriched in zinc and dynorphin B which appear to be concentrated in mossy fiber terminals in vivo. Synaptosomes isolated by this procedure accumulated 2 deoxyglucose and retained 88% of total lactate dehydrogenase activity after incubation at 30 degrees C for 60 minutes, indicating a high degree of membrane integrity. Oxygen consumption was stimulated 4-fold by veratridine (0.1 mM) and inhibited 90% by ouabain (1 mM), suggesting that synaptosomal metabolism remained tightly coupled to ouabain-sensitive ATPase activity. Potassium-stimulated (45 mM) release of dynorphin B was completely dependent upon the presence of extrasynaptosomal calcium, while only 30% of the evoked release of glutamate was calcium-dependent. D-aspartate, which exchanges glutamate out of the cytoplasmic pool, virtually eliminated the calcium-independent component of glutamate release. This synaptosomal preparation will be useful in identifying the factors that modulate the release of amino acid and opioid neurotransmitters from hippocampal nerve terminals and in the investigation of their presynaptic mechanisms of action. PMID- 2905628 TI - Measurement of intracellular Ca2+ in cerebellar Purkinje neurons in culture: resting distribution and response to glutamate. AB - Ca ion levels in cerebellar Purkinje neurons, in culture, have been measured using the fluorescent indicator, fura-2, and digital imaging. Cells were loaded with the indicator both by injecting the free acid form and by allowing the membrane permeant form (/AM) become deesterified and trapped. The two methods gave significantly different results in that the /AM loaded cells showed localized regions of high Ca2+ in the soma whereas the injected cells did not. Resting levels in the remainder of the cytoplasm were similar however, as were the excursions in Ca2+ induced by electrical or chemical stimulation. Comparison of the data from the two methods suggests that qualitative measures of Ca in intracellular stores can be derived from the /AM loading method. Injected cells showed high Ca2+ levels in the soma that persisted for 3-8 minutes following removal of the injection electrode. The dendrites of these cells however maintained low Ca2+ levels and differences of several hundred nM in Ca2+ were maintained between the soma and initial dendrite segment, demonstrating directly the large Ca pumping capacity of the dendrites. Localized regions of high Ca2+ in dendrites could be generated by applying glutamate from a microelectrode in TTX Krebs saline. When studied in culture media with 4.7 mM K, the Purkinje neurons showed a biomodal distribution of Ca2+ with 35 to 40% showing stable Ca2+ levels between 250 and 350 nM, and the remainder 80 to 130 nM Ca2+. Granule neurons on the same coverslips had Ca2+ level in the lower range in greater than 95% of the examples observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2905630 TI - Montreal to host V International Conference on AIDS in June 1989. PMID- 2905629 TI - [Postoperative agitation. A new cause]. AB - Thirty-three patients, operated on between 1981 and 1986, and presenting post operative confusion and restlessness are analyzed. Two groups are identified: group 1 are patients who regularly received BZD before their present hospitalization; in group 2 patients were given high-dose BZD in the early postoperative period. Symptoms were anxiousness in 15 patients, restlessness in 14, myoclonia in 14, delirium in 3, coma and seizures in 1. BZD withdrawal syndrome was considered after the other causes of post-operative agitation were eliminated and the diagnosis was confirmed by the administration of BZD that relieved the symptoms and by the plasmatic concentration of BZD. This syndrome appears 1 to 5 days after BZD withdrawal and severity of symptoms seems to be directly proportional to the doses and duration of BZD therapy. Propranolol was proposed to reduce the intensity of the symptoms. Nevertheless, progressive withdrawal of BZD remains the best way for managing such patients. PMID- 2905631 TI - Binding of [3H]befunolol to beta-adrenoceptors in cardiac muscles of fetal and neonatal rat. AB - Characterization of beta-adrenoceptors was studied in heart muscles of rat fetus and neonate. The results of binding assay with [3H]befunolol, a beta-adrenergic partial agonist, to membrane fractions from rat heart muscles indicate that beta adrenoceptors contain two different affinity sites. In the presence of 5' guanylylimidodiphosphate, the low affinity site was reduced, while the high affinity site was not affected. The dissociation constants for both sites did not change during pre- and post-natal development. But the maximum binding sites for both sites decreased slightly but significantly (p less than 0.05) during development. A 10-fold decrease in norepinephrine sensitivity and isoprenaline sensitivity during pre- and post-natal development was not explained by the slight decrease in the maximum binding sites. PMID- 2905632 TI - Relationship of adverse drug reactions to length of hospital-stay in genetically subgrouped schizophrenics. AB - The emergence of depression, parkinsonism, and akathisia after neuroleptic therapy was associated with increased length of hospital-stay in schizophrenics with affective heredity only. In schizophrenics with schizophrenic heredity, increased length of hospital-stay was associated with residual hallucinations and apathy. In the former patients, findings were theoretically attributed to a putative biogenetic abnormality sensitive to the effects of neuroleptic drugs. PMID- 2905633 TI - Depolarization induced by bethanechol in hamster submandibular ganglion cells. PMID- 2905634 TI - The electrogenesis mechanism of inhibitory muscarinic response induced by bethanechol in hamster submandibular ganglion cells. PMID- 2905635 TI - Effects of alpha l- and alpha 2-adrenoceptor antagonists on noradrenaline responses of hamster submandibular cells. PMID- 2905637 TI - [Monitoring trace organic components of human expired air and observation of their variability]. PMID- 2905636 TI - Comparative analgesic efficacy and tolerability of ketorolac tromethamine and glafenine in patients with post-operative pain. AB - In a randomized, single-dose, double-blind, parallel comparative trial of analgesic efficacy, 96 adult patients received either 10 mg ketorolac tromethamine or 400 mg glafenine orally the morning after surgery if they requested pain relief medication. Each patient provided a baseline pain assessment and then received the assigned medication. Patients assessed pain intensity and pain relief and reported any adverse events in interviews held 30 minutes after drug administration and then hourly for 6 hours. The demographic characteristics, baseline pain intensity, and surgical categories of the 47 patients who received ketorolac tromethamine and the 49 who received glafenine were similar. Both drugs provided prompt, sustained pain relief throughout the 6 hour observation period, and there were no statistically significant differences between the two groups in any of the efficacy measures analyzed. The global assessment recorded by patients suggested a slight clinical advantage for ketorolac tromethamine (32.6% of 'excellent' responses) as compared to glafenine (12.5% 'excellent'). The differences in overall response were statistically significant (p = 0.017). Fourteen (30%) patients who received ketorolac tromethamine and 17 (35%) who received glafenine reported adverse experiences that began or seemed to worsen after administration of the study drugs. The most prominent were drowsiness and sleeping, both of which are common in post-surgical patients. PMID- 2905638 TI - HPLC reveals famotidine in the urine up to five days after a single 20 mg oral dose. AB - Using a simple method for the HPLC determination of famotidine (FMTD), a new inhibitor of histamine H2-receptors, it is possible to evaluate the urine levels of the drug in patients undergoing treatment. FMTD is excreted mostly in the urine, in the unmetabolized form. The authors evaluated the endpoint of FMTD levels in the urine in five patients given a single oral dose of 20 mg and found measurable levels of the drug up to 106 h (5 days) after the patients began the medication. This method may be useful for assessing patient compliance in taking the drug: this will allow the gastroenterologist to distinguish patients with true relapses of peptic ulcer disease from false relapses, in clinical trials using this histamine H2-inhibitor. PMID- 2905639 TI - Comment: peptic ulcer H2-receptor antagonist therapy. PMID- 2905641 TI - Ocular metipranolol. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in glaucoma and ocular hypertension. AB - Metipranolol is a non-selective beta-adrenoceptor blocking agent used for the topical treatment of elevated intraocular pressure in patients with chronic open angle glaucoma or ocular hypertension. In double-blind comparative studies of up to 4 months duration, metipranolol 0.1 to 0.6% produced comparable reductions in intraocular pressure to timolol 0.25 to 0.5% and levobunolol 0.5%, lowering pressure by about 20 to 29% from baseline. Metipranolol has been well tolerated by most patients, producing only minor changes in objective measurements of ophthalmic status and systemic parameters. Similarly, subjective ophthalmic complaints have been minimal although reports of initial stinging or burning upon instillation have occurred. Further published reports, in which larger numbers of patients are treated over extended periods, are needed to confirm the drug's apparent long term comparative efficacy. Studies of ocular metipranolol to date are encouraging, and the drug demonstrates a lasting intraocular pressure reducing effect with good tolerability. Thus, ocular metipranolol provides a viable alternative to ocular timolol and levobunolol in the topical treatment of chronic open angle glaucoma or ocular hypertension. PMID- 2905640 TI - Nizatidine. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic use in peptic ulcer disease. AB - Nizatidine is an H2-receptor antagonist which in animal studies was more active on a weight-for-weight basis than cimetidine in inhibiting basal and stimulated gastric acid secretion. Similarly, studies in humans have confirmed that nizatidine is a potent inhibitor of basal, nocturnal and stimulated gastric acid secretion. As might be expected at this stage of its development, published therapeutic experience with nizatidine is limited. Nevertheless, multicentre therapeutic trials have shown that nizatidine 300mg at bedtime or 150mg twice daily is significantly more effective than placebo for healing active duodenal ulcer, and is apparently as effective as standard doses of ranitidine in increasing the rate of healing of both duodenal and gastric ulcers, and as effective as a standard dose of cimetidine in active duodenal ulcer. When used prophylactically a single 150mg dose of nizatidine at night produces a decrease in the incidence of ulcer recurrence compared with placebo, and a similar rate of decrease to that achieved with ranitidine 150mg. Nizatidine is well tolerated. Unlike cimetidine it does not have any antiandrogenic effects or alter the hepatic metabolism of drugs. However, only wider clinical experience with nizatidine can accurately determine its relative efficacy and tolerability compared with other antiulcer therapy. Thus, early clinical experience suggests that nizatidine is a useful alternative to the histamine H2-receptor antagonists presently in clinical use. PMID- 2905642 TI - [Tardive dyskinesia and affective disorders]. AB - The authors analyse the relations between tardive dyskinesias and affective disorders on the basis of epidemiological, clinical and biological arguments. They review the principal data in the literature and develop some hypotheses concerning the explanation of these relations. PMID- 2905643 TI - [Dopaminergic modifications caused by neuroleptics. Functional and therapeutic hypotheses on tardive dyskinesias]. AB - While neuroleptic action cannot be reduced to a single effect, the fact that their clinical consequences may be linked to dopaminergic receptor binding (DA) has now gained widespread acceptance. There are at least two types of DA receptors (D1 and D2), each of which is a different molecular entity. D1 receptors activate adenylate cyclase via the intermediary of a Gs protein whereas D2 receptors may either inhibit adenylate cyclase when bound to Gi or Go proteins or play a role in opening the ion channel or in the phosphatidylinositol cycle via the intermediary of a G translating protein, the existence of which has recently been demonstrated. In the short run, DA receptor blockade induces depolarization of DA neurons together with an increase in DA synthesis and release followed, in the case of nigro-striatal neurons, by "hyper depolarization" inducing a drop in DA synthesis and release. This phenomenon, mistakenly called "tolerance", also exists in meso-limbic neurons but not in meso cortical neurons. In the longer run, chronic blockade of DA receptors by neuroleptics induces hypersensitivity linked to an increase in the number of receptor sites. This hypersensitivity, detected by behavioural, electrophysiological and biochemical methods, is evident for sub-cortical structures but has not yet been firmly established for the cortex. The nature of this hypersensitivity could be identical to that observed in denervation experiments. Nonetheless, in certain already controversial studies, the mechanism involved in denervation hypersensitivity and that induced by repeated dosing with neuroleptics are distinct, a cumulation of effects having been observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2905644 TI - [Animal models of tardive dyskinesia]. AB - It is possible to induce in monkeys abnormal movements of the mouth and tongue resembling strikingly tardive dyskinesia. Such movements can be induced by chronic treatment with neuroleptics or by lesions placed in the habenular interpeduncular tract or nucleus parafascicularis thalami. Dopaminergic D1 and D2 receptors are involved in the modulation of such movements. PMID- 2905645 TI - [The electrophysiological approach to tardive dyskinesias]. AB - Electrological study of TD is of value on two counts: it facilitates diagnosis in cases where the origin of the dyskinesia is not known, it enables objective monitoring of therapeutic studies. TD electromyographic recordings are highly specific. The recording shows: either, continuous activity of irregular amplitude corresponding to that which is called "tardive dystonia" in a clinical context, or, discontinuous irregular activity sometimes grouped into bursts of activity of relatively long duration, with a rhythm of 0.5 to 2 Hz during the temporal sequences, which are of variable duration. This type of activity is the same as that found in movements induced by L-dopa (L-dopa IM). In both cases, these involuntary movements only occur after several months' or years' treatment. They predominate in the oro-facial region. However, reactions to various pharmacological agents are not identical. While activity is decreased by neuroleptics and increased by L-dopa, anticholinergics have no effect on L-dopa IM whereas they exacerbate TD. GABA decreases TD but is ineffective against L dopa IM. The reaction of these movements to L-dopa and neuroleptics, suggests that both reflect hypersensitivity to dopamine. Their different reactions to GABA lead one to suppose that GABA modulation of the dopaminergic system is defective in TD. PMID- 2905646 TI - [Neuroleptic-induced tardive dyskinesias in France]. AB - In France chlorpromazine was used as soon as 1952, and TD were described very early (Ey et al., 1956; Sigwald et al., 1959). Nevertheless there is very little interest in this complication of neuroleptic treatment. The mild oral syndrome is neglected and severe TD considered as very rare, due to lower dosage of neuroleptics in France. We summarize several inquiries: Maurel et al. (1966; prevalence = 49%), Bourgeois (1976-1977; 8.1%), Bourgeois et al. in a sample of 270 elderly (prevalence = 42.4% with neuroleptics; 18% in patients who never received neuroleptics), Delance (1985 = 16%), Fanget et al. (1986; 3.8%). PMID- 2905647 TI - [Epidemiology of tardive dyskinesias in the Maghreb]. AB - The most prescribed type of psychotropic medication in maghrebian psychiatry is neuroleptics. It is therefore legitimate to study the epidemiology of the most frequent side-effect of long-term treatment with neuroleptics: Tardive Dyskinesia (TD). At the moment, a collaborative study is under way on epidemiology of TD within the framework of the Maghrebian Association of Biological Psychiatry; several studies have also been conducted on this topic in the University Psychiatric Centre Ibn Rochd, Casablanca, Morocco in 1984, 1986 and 1987. For the maghrebian study, only preliminary results from Tunis will be presented. These studies have been interested in two epidemiological aspects: prevalence of TD in hospitalized and out-patients treated with neuroleptics; prevalence of TD-like movements among never treated schizophrenics. The assessment tool used for all the studies was the Abnormal Involuntary Movement Scale (AIMS). Main results of these studies are: 1) General prevalence of TD and risk factors in neuroleptized patients: In Tunis, Douki and Benamor in their on-going study, found a general prevalence of 20.50% (N = 200 in patients). A multi-factor analysis showed that risk factors are (in decreasing order): female gender, age above 60, associated depression, total duration of neuroleptic treatment above 20 years, a frequently discontinued treatment, shock therapies in antecedents or associated, a diagnosis of non schizophrenic psychosis, haloperidol intake below 25 mg and fluphenazine depot above 100 mg daily. In Casablanca, in 1984, Chorfi found a general prevalence of 10% (N = 50 out-patients). In 1986, Bentounsi found a 14.50% prevalence in Casablanca (N = 400 out-patients) and 63.97% in the oldest psychiatric hospital in Morocco in Berreshid (N = 605 in-patients).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2905648 TI - [Clinical aspects of tardive dyskinesias induced by neuroleptics]. AB - Initially, the reality of the existence of tardive dyskinesia raised some controversy, but rapidly this syndrome was recognized as a complication arising from usually long-term administration of neuroleptics. These extrapyramidal abnormal movements represent an important problem due to their prevalence, their potential irreversibility, their complex and still disputed physiopathologic mechanism, the absence of specific and generally effective treatment, and more recently the medico-legal problems entailed. At first, it was believed that these dyskinetic movements, of various intensity, were localized only at the oro-facial area (face, tongue, maxillary), or consisted of limited or generalized choreo athetosic movements, or were a mixture of both types of movements. However, digestive and respiratory tardive dyskinesia also occur. Tardive dyskinesia can develop insidiously during neuroleptic treatment, or appear when this medication is decreased or ceased. It can coexist with parkinsonian signs. Age (over 50) and gender (female) appear to be risk factors. Other types of tardive syndromes associated with neuroleptic administration have been reported, such as tardive akathisia, tardive dystonia and a tardive Tourette-like syndrome. Involuntary movements resembling tardive dyskinesia can be observed in elderly individuals who never received neuroleptic medication. With respect to the rabbit syndrome, a rapid tremor of the perioral area, with a rhythmicity similar to the parkinsonian tremor, it is clearly different from tardive dyskinesia. It is essential to detect as precociously as possible tardive dyskinesia. The diagnosis is sometimes difficult and even if the clinical features seem pathognomonic of tardive dyskinesia, it is nevertheless important to establish a differential diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2905649 TI - [Senile dyskinesias and tardive dyskinesias]. AB - Correct recognition of spontaneous linguobucco-facial dyskinesia is at least of interest in that it enables accurate evaluation of the impact of neuroleptic medication on the occurrence of similar neurological disorders. Since 1963, first anecdotal evidence and then series of cases of spontaneous dyskinesia have been reported. This has enabled evaluation of the prevalence of these disorders in subjects aged over 60 to be determined as 10% whereas incidence is over 50% in subjects of the same age receiving neuroleptics. Nonetheless, a number of uncertainties persist. Epidemiological studies produce very variable results suggesting that the concept of tardive dyskinesia is not always adequately defined and that certain disorders of a different type are sometimes confused with that condition. Dyskinetic movements involve the face and trunk, like those of chorea, but do not share the latters' abrupt rapid and unpredictable nature. Dyskinetic movements on the contrary, tend toward a degree of reproducibility, if not stereotypy, in the manner of ballistic movements which may be distinguished by their rotary character and the fact that they are generally localized in one half of the body. Lastly dyskinetic movements frequently have the creeping appearance of athetoid movements from which they may be distinguished by case history. The various characteristics confer a highly specific appearance on dyskinetic movements which was well described by Sigwald back in 1959. It should be stressed that author, who had already studied bucco-lingual dyskinesia in epidemic encephalitis in 1953, discovered, with surprise, the existence of such disorders in an infectious context.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2905650 TI - Affective disorders and tardive dyskinesia. AB - Evidence from multiple lines of study indicate that mood disorders, particularly depression, are a risk factor for developing tardive dyskinesia (TD). Important patient and treatment factors include: 1) frequent retrospective rediagnosis of affective disorders instead of schizophrenia when the long-term course of illness and response is evaluated, and 2) TD onset after relatively brief (few months to few years) exposure to low to moderate neuroleptic doses. Mechanisms underlying this increased sensitivity to TD are unknown. It has been hypothesized that the cyclic mono- and catecholamine activity during mood changes makes the brain more vulnerable to the direct neuroleptic effects or the compensatory processes initiated by these drugs. There may also be an interaction between neuroleptic drugs and antidepressant agents which produce greater vulnerability to TD. Additionally, neuroleptic drug use may be different in affective disorders, such as high doses for short time periods with mania. Treating TD in patients with mood disorders is often difficult. The psychiatric diagnosis should be the first priority in treatment regimens. Then, strategies for addressing TD should be considered. Occasionally lithium and/or antidepressants may be effective in treating both affective disorders and TD in some patients. Specific drug therapies for TD have not been consistently effective. Therefore, the passage of time may be the best treatment approach. Preventing TD should receive the highest priority. In the short term, neuroleptic drugs should be limited to managing acute psychotic symptoms in patients with mood disorders. In the long term, neuroleptics should be reserved for manic or depressive symptoms that do not respond to standard therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2905651 TI - Tardive dyskinesia. Pathophysiological mechanisms and clinical trials. AB - Recent observations from human and animal studies indicate that the traditional dopamine supersensitivity theory in tardive dyskinesia (TD) is insufficient. Instead, a new hypothesis is proposed: TD may be due to an increased D-1 receptor function or an increased ratio between D-1/D-2 receptor functions in the brain, maybe associated with a diminished activity in certain striatofugal GABA neurons. This hypothesis is based on experiments with selective D-1 and D-2 drugs in rodents and monkeys, but has not yet been tested clinically due to lack of D-1 agonists and antagonists for human use. In a Nordic multicenter study, various neuroleptics (haloperidol, perphenazine, chlorprothixene) were given to 33 elderly psychiatric patients with TD. The main result of this study was the demonstration of 1) an inverse relationship between parkinsonism and TD, and 2) an inconsistent response to withdrawal of various neuroleptics. Following withdrawal, 38% of the patients had a TD aggravation, 27% a TD reduction, and 35% no TD change, all compared with the TD level before the neuroleptic test period and independent of the neuroleptic given. This observation speaks against the dopamine hypersensitivity theory and is more in accordance with the new hypothesis proposed above. The GABA part of the TD hypothesis has been tested with different GABA agonists such as gamma-acetylenic GABA, gamma-vinyl GABA and THIP, but most studies suggest that the therapeutic effect of these drugs in TD is limited and maybe secondary to parkinsonism and sedation. Clinicians are eagerly awaiting new GABA agonists with selective affinity to subgroups of GABA receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2905652 TI - Preventing neuroleptic-induced tardive dyskinesia in adults and children. AB - Neuroleptics remain useful in the treatment of schizophrenia, but tardive dyskinesia (TD) is a recognized serious side effect of long-term neuroleptic use in adults and children. Lack of proven effective treatment for TD makes prevention of TD a focus of clinical attention. In order to provide guidelines for the clinician, the literature regarding epidemiological risk factors for TD is reviewed. Clinical strategies for prevention of TD are discussed based on principles of: 1) being aware of risk factors for TD; 2) evaluating neuroleptic treatment; and 3) detecting early TD. The importance of patient participation in the clinical decision for long-term neuroleptic therapy cannot be overstressed. PMID- 2905653 TI - Legal aspects of tardive dyskinesia. AB - While the therapeutic value of neuroleptics in the treatment of schizophrenia and psychoses is universally recognized, the risk of tardive dyskinesia linked to the use of these drugs raises ethical and legal problems for the physician. The authors discuss the basic principles linked to these legal aspects of the question: inappropriate indication of neuroleptic treatment, inadequate treatment monitoring, error in diagnosis of tardive dyskinesia and misconduct with regard to informed consent. The various aspects are illustrated by specific cases. PMID- 2905654 TI - A summary of current knowledge of tardive dyskinesia. AB - Tardive dyskinesia (TD); abnormal involuntary movements appearing late in neuroleptic treatment) was described shortly after introduction of chlorpromazine and other antipsychotic agents in the 1950s. Consideration of this disorder as a common, progressive, and relentless problem of major public-health and medicolegal concern in the 1970s now appears to have been somewhat exaggerated. Several symptom patterns associated with neuroleptic treatment may or may not appropriately be lumped with the concept of TD (acute and withdrawal-emergent dyskinesias, dystonias, and akathisia, in particular); parkinsonism (with bradykinesia, rigidity, and tremor, including perioral tremor of the "rabbit syndrome") should be differentiated from TD, even though elements of both may occur together. Dyskinesias, more or less similar to TD, can occur in chronically ill neuropsychiatric patients not exposed to neuroleptics. Some may represent stereotyped behaviors of schizophrenia or undiagnosed neurological disorders, but a risk of spontaneous dyskinesias indistinguishable from TD averages about 5% (probably less in young patients). Mean prevalence rates for TD, corrected for spontaneous dyskinesias, average about 15-20% with higher risks at advancing ages. Incidence rates are less certain, but estimates average about 5% a year for at least several years in young patients, with higher rates within the first two years of treatment of elderly patients. Risk factors most clearly defined are advancing age, use of neuroleptic agents at relatively high daily doses for more than six months, and perhaps the diagnosis of a major affective disorder. Female gender and relatively high plasma levels of neuroleptic agents are less significant risk factors and other metabolic or neuroradiological indicators of risk remain unproved. The etiology of TD remains obscure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2905655 TI - [Hepatic encephalopathy]. PMID- 2905656 TI - Prenatal DNA analysis in four embryos/fetuses at risk of 21-hydroxylase deficiency. AB - Prenatal diagnosis of 21-hydroxylase deficiency (21-OHD) in two unrelated embryos and two fetuses was attempted with the Southern hybridization method using the 21 hydroxylase (21-OHase) complementary DNA as a probe. The two embryos whose genomic DNA was extracted from their chorionic villi both had four TaqI fragments (3.7 kb, 3.2 kb, 2.4 kb and 2.3 kb) identical to those of their respective parents and normal controls, while the DNA from each proband of these two families lacked with the 3.7 kb and the 2.3 kb fragments corresponding to the functional 21-OHase gene (21-OHase B gene). These findings indicated that none of the embryos examined were deletion homozygotes for the 21-OHase B gene. In the two fetuses, only amniotic fluid cells were available for prenatal diagnosis. The results of Southern hybridization analysis were uninformative since all family members, including the probands and fetuses, had all four TaqI fragments. Linkage studies between 21-OHD and human leukocyte antigen (HLA) haplotypes and those between the disease and restriction fragment length polymorphisms of the 4th complement gene revealed that the fetus of one family was normal. The other fetus could not be diagnosed because a recombination between the class I HLA and the 21 OHD loci had occurred in this family. PMID- 2905657 TI - Spontaneous kidney rupture in polyarteritis nodosa. Report of four cases. AB - Spontaneous kidney rupture as the initial manifestation of polyarteritis nodosa is rare. We present 4 such patients who underwent nephrectomy. We suggest primary nephrectomy in patients with spontaneous kidney rupture and resultant retroperitoneal hematoma in whom no preoperative diagnosis is available. PMID- 2905658 TI - The alpha 2-adrenoceptor antagonist activity of ipsapirone and gepirone is mediated by their common metabolite 1-(2-pyrimidinyl)-piperazine (PmP). AB - Ipsapirone and gepirone, analogs of buspirone, a newly developed antianxiety agent, form 1-(2-pyrimidinyl)-piperazine (PmP) during their biotransformation in rats. After oral administration (10 mg/kg) of a parent drug, e.g. ipsapirone or gepirone, the metabolite appears in significant amounts in plasma, with maximal concentrations of 0.9 and 1.4 nmol/ml respectively. The metabolite half-life ranged from about 140 to 200 min. Ipsapirone is eliminated more slowly than gepirone, with a half-life of about 100 and 30 min, respectively. The metabolite to parent drug ratios for the areas under the plasma concentration-time curve (AUC) were 1 for ipsapirone and 14 for gepirone. PmP (0.5-2 mg/kg p.o), ipsapirone, gepirone and buspirone (5-20 mg/kg p.o.) dose dependently antagonized the slowing of gastrointestinal transit induced by clonidine 0.1 mg/kg s.c. The doses inhibiting the antitransit effect of clonidine by 50% were 0.8 mg/kg for PmP, 14 mg/kg for ipsapirone and 9 mg/kg for both gepirone and buspirone. Analysis of small intestinal longitudinal muscle of rats given the ED50 of PmP, ipsapirone, gepirone, buspirone showed that PmP concentrations in the longitudinal muscle (with attached myenteric plexus) fell within a relatively narrow range and were consistent with the appropriate transit scores. The plasma was also tested for anticlonidine activity. These data indicate that PmP formation is a pharmacologically significant metabolic process for the buspirone related drugs, ipsapirone and gepirone, and that this metabolite is responsible for the alpha 2-adrenoceptor blocking activity exerted by these drugs in vivo in the rat. PMID- 2905659 TI - Somatostatin and SMS 201-995 reverse the impairment of cognitive functions induced by cysteamine depletion of brain somatostatin. AB - The involvement of somatostatin in the organization of cognitive functions was studied. We assessed changes in learning and memory processes by studying the effects of cysteamine, a compound that decreases somatostatin-like immunoreactivity in the brain, somatostatin and the potent somatostatin analogue, SMS 201-995, on active avoidance behaviour, assessed with a shuttle box apparatus, or on passive avoidance behaviour. Cysteamine induced a loss of the conditioned active avoidance response acquired after 3 weeks of daily trials. The effect was observed 2 h (-29%) and 4 h (-51%) after cysteamine treatment (300 mg/kg s.c.) and disappeared after 24 h. Intracerebroventricular administration of somatostatin or SMS 201-995 to cysteamine-treated rats significantly reversed the cysteamine effects on the conditioned avoidance responses. Similar results were obtained on passive avoidance behaviour. We also investigated the effect of cysteamine treatment on brain somatostatin-sensitive adenylate cyclase. We observed that adenylate cyclase activity in the frontal cortex of cysteamine pretreated animals was more sensitive to inhibition by the SRIF analogue, SMS 201 995, than it was in control animals. This effect was observed at concentrations of SMS 201-995 that were ineffective in control tissue. These results show that disruption of somatostatinergic transmission affects cognitive functions of rats. PMID- 2905660 TI - Characterization of kappa opioid receptors in the rabbit ear artery. AB - Quantitative characterization of the kappa opioid receptor in the rabbit ear artery was carried out using three kappa-selective agonist compounds, dynorphin (1-13), U-69593 and ethylketocyclazocine. Kinetic analysis was performed using the antagonist, MR 2266. Two other in vitro preparations were studied for comparison: the mouse was deferens and rabbit was deferens. To avoid mu receptor action in the mouse was deferens the irreversible mu receptor antagonist, beta funaltrexamine, was used. It was demonstrated that, using the highly selective kappa agonist compound U-69593, Ke values for MR 2266 obtained in the three assay systems were not significantly different. These results suggest that kappa receptors present in these three tissues share identical properties. PMID- 2905661 TI - Antagonism of serotonin receptor mediated neuroendocrine and temperature responses by atypical neuroleptics in the rat. AB - The ability of atypical and typical antipsychotics to antagonize serotonin (5-HT) receptor-mediated temperature and neuroendocrine responses was tested in rats. Clozapine, melperone and setoperone, three atypical neuroleptics, blocked in a dose-dependent manner, the hyperthermic response to the 5-HT agonist, MK-212, whereas chlorpromazine and haloperidol were ineffective. The hypothermic response to the 5-HT1A agonist, 8-OH-DPAT, was unaltered by any of the atypical neuroleptics tested. Similarly, MK-212-induced corticosterone secretion was blocked in a dose-related manner by clozapine, melperone and setoperone but was relatively unaffected by either haloperidol or chlorpromazine. The increase in corticosterone secretion observed following 8-OH-DPAT administration was not attenuated by pretreatment with the atypical or typical antipsychotics tested. These data indicate that atypical neuroleptics are effective 5-HT2 but not 5-HT1A antagonists in vivo. Conversely, the typical neuroleptics, haloperidol and chlorpromazine do not block the 5-HT receptors involved in activation of the hypothalamic-pituitary-adrenal axis or thermoregulation. PMID- 2905662 TI - Changes in the limbic neurotensin systems induced by dopaminergic drugs. AB - Single or multiple high doses of the dopamine-releasing drug, methamphetamine, induced 100-150% increases in the content of neurotensin-like immunoreactivity (NTLI) in the nucleus accumbens, but was without effect on the NTLI level in the ventral tegmental area. The increases in NTLI content in the nucleus accumbens were selectively blocked by the dopamine D-1 receptor antagonist, SCH 23390, which failed to exert any significant effect of its own in the same area. In contrast, haloperidol or the selective dopamine D-2 antagonist, sulpiride, when administered alone, significantly raised the NTLI level in the nucleus accumbens and when given concomitantly with methamphetamine, their effects on the amount of NTLI appeared to be additive. Very different patterns of response were observed in neurotensin systems associated with the mesocortical dopaminergic terminal fields of the frontal cortex and olfactory bulbs. Changes in NTLI contents occurred following only multiple doses of methamphetamine and consisted of decreases in levels of this peptide. However, like the nucleus accumbens, these methamphetamine-induced alterations were blocked completely by D-1 antagonism, while D-2 blockade appeared to be additive with the effects of methamphetamine. PMID- 2905663 TI - Antagonism of the responses to isoproterenol in the rat hippocampal slice with subtype-selective antagonists. AB - The electrophysiological and cAMP responses to the beta-adrenoceptor agonist isoproterenol were measured in the in vitro hippocampal slice preparation. Subtype-selective antagonists were used to evaluate the specificity of these responses. The beta 1-selective antagonist ICI 89,406 was 60-fold more potent than was the beta 2-selective antagonist ICI 118,551 at antagonizing the electrophysiological response. ICI 89,406 was 200 times more potent in its antagonism of the cAMP response. These results suggest that the electrophysiological and cAMP responses in this preparation are primarily mediated by beta 1-adrenoceptors. PMID- 2905664 TI - Benzodiazepine receptors studied in living primates by positron emission tomography: antagonist interactions. AB - After labelling the brain benzodiazepine receptors of sub-human primates with [11C]RO15-1788, the interactions of different benzodiazepine receptor antagonist ligands were studied by positron emission tomography (PET). Various doses of either RO15-1788, RO15-3505 or propyl beta-carboline-3-carboxylate were injected intravenously 20 min after the radiotracer, and induced an immediate and specific dose-dependent displacement of the brain radioactivity. However, a comparison of the dose-receptor occupancy patterns of these three antagonists established from the displacement experiments revealed that only propyl beta-carboline-3 carboxylate displayed clear biphasic dose-receptor occupancy curves. This indicates that, in the living primate brain, there are two different benzodiazepine receptor subpopulations (which can be either different benzodiazepine receptor subtypes or distinct conformational states of a single receptor). PMID- 2905665 TI - Hindlimb paralytic effects of prodynorphin-derived peptides following spinal subarachnoid injection in rats. AB - Dynorphin A-(1-17) acts through non-opioid mechanisms to produce dose-related neurological deficits following injection into the lumbar spinal subarachnoid space in rats. Hindlimb motor function was examined following subarachnoid injection of dynorphin A fragments and other opioid peptides derived from prodynorphin to establish: (1) which portion(s) of the dynorphin A molecule cause hindlimb motor dysfunction, and (2) whether these paralytic actions are shared by other opioids (dynorphin B, alpha-neo-endorphin, and beta-neo-endorphin) derived from the same promolecule. To minimize the influence of enzymatic inactivation on relative bioactivities, peptides were coinjected with a combination of peptidase inhibitors previously shown to enhance the actions of dynorphin A fragments in vitro. Dynorphin A-(1-17) and -(2-17) produced dose-related neurological deficits with equal potencies and durations. Although without effect when injected alone, dynorphin A-(1-8), -(1-7) and -(3-8) caused transient motor dysfunction when co injected with peptidase inhibitors. In contrast, dynorphin A-(1-6), -(1-5) and (6-17) did not disrupt hindlimb motor function with or without peptidase inhibition. Dynorphin B, alpha-neo-endorphin and beta-neo-endorphin also caused hindlimb dysfunction which was potentiated by peptidase inhibition. These deficits appeared to result from non-opioid actions of these three peptides, since they were not blocked by the opioid antagonist naloxone. Thus, the paralytic effects of dynorphin A: (1) result from non-opioid actions involving the 3-7 or 3-8 positions of the molecule, and (2) are shared by other prodynorphin-derived opioid peptides. PMID- 2905666 TI - Specific receptors for bradykinin-induced cardiac sympathetic chemoreflex in the dog. AB - Bradykinin (BK, 0.03-1 microgram), capsaicin (1 microgram) or potassium chloride (KCl, 13 mumol) applied to the epicardium of the left ventricle of anaesthetized, open-chest dogs, caused reflex tachycardia and pressor effects, whereas des-Arg9 BK (1-100 micrograms), a selective bradykinin B1-receptor agonist, failed to produce any cardiovascular response. Superfusion of the epicardium with a selective B1-receptor antagonist, des-Arg9-[Leu8]BK (50-100 micrograms/min) had no effect on reflex responses to epicardial BK (0.03-0.1 microgram). However, the selective B2-receptor antagonist, D-Arg-[Hyp3,Thi5,8,D-Phe7]BK (10-25 micrograms/min) abolished the reflex effects of 0.03 and 0.1 microgram BK and reduced by 50 to 70% the responses to 1 microgram BK. Another B2-receptor antagonist [Thi6,9,D-Phe8]kallidin (10-50 micrograms/min) also reduced (30-70%) responses to 1 microgram BK. The antagonism was reversible and specific for BK since reflex responses to epicardial application of either capsaicin or KCl were not affected. The results indicate that BK interacts with B2-receptors, probably located on terminals and/or axons of sympathetic afferents supplying the dog heart, to activate a cardiac sympathetic chemoreflex. PMID- 2905667 TI - Evidence for two independent modes of activation of the 'efferent' function of capsaicin-sensitive nerves. AB - Field stimulation (10 Hz for 10 s, 0.5 ms pulse width, 60 V) of the guinea-pig isolated main bronchi (atropine plus indomethacin in the bath) produced reproducible contractions which were abolished by tetrodotoxin or in vitro capsaicin desensitization. These responses were almost abolished by omega conotoxin GVIA (CTX), a peptide modulator of neuronal calcium channels which, however, did not affect the bronchial contraction due to neurokinin A or to capsaicin. Field stimulation (10 Hz for 2.5 s, 1 ms, 60 V) of the electrically driven, isolated guinea-pig left atria excised from reserpine-pretreated animals (atropine in the bath) produced a delayed positive inotropic response which was abolished by tetrodotoxin or in vitro capsaicin desensitization. This response was abolished by CTX, which did not affect the response to exogenous calcitonin gene-related peptide nor that to capsaicin. These findings indicate that CTX sensitive mechanisms (presumably Ca channels regulating the release of transmitters) are activated upon antidromic invasion of sensory terminals and consequent production of the 'efferent' response while the activation of sensory nerve endings by capsaicin occurs through CTX-resistant mechanisms. PMID- 2905668 TI - Effects of locally applied D-1 and D-2 receptor agonists and antagonists studied with brain dialysis. AB - The effect on dopamine (DA) release of D-1 and D-2 receptor agonists and antagonists applied locally in the caudate through a trans-striatal dialysis probe was studied in freely moving rats. D-2 agonists (LY 171555 and BHT 920) reduced DA release in a concentration-dependent manner. The same local application of haloperidol abolished the effect of 10 microM LY 171555 and BHT 920. A specific D-1 agonist, the catechol benzazepine SKF 38393, reduced DA release and this effect was not modified by systemic or local administration of the D-1 antagonist, SCH 23390, nor by the D-2 antagonist, haloperidol. In contrast, the non-catechol D-1 agonist, CY 208243, failed to modify DA release. Local application of the D-1 antagonist, SCH 23390, or of the D-2 antagonist, (-) sulpiride, stimulated DA release in a concentration-dependent manner. The D-1 agonist, CY 20843, reversed the stimulatory effect of SCH 23390 but not that of ( )-sulpiride. It is concluded that D-1 and D-2 receptors located in the caudate control DA release separately in this area. PMID- 2905669 TI - Impact of climate on western equine encephalitis in Manitoba, Minnesota and North Dakota, 1980-1983. AB - Information was collected on confirmed outbreaks of western equine encephalitis (WEE) in North America east of the Rockies for 1981 and 1983 (epidemic years) and 1980 and 1982 (non-epidemic years). The initial pattern of outbreaks in Manitoba, Minnesota and North Dakota was determined for each year. Backward (and in some instances forward) wind trajectories were computed for each day 4-15 days (incubation period) before the initial outbreaks of WEE in a given area of province or state. During these years the timing and location of WEE outbreaks in horses and man, seroconversion in chickens, the maximum Culex tarsalis counts at Winnipeg and first isolation of WEE virus from C. tarsalis could be correlated with trajectories of winds from states further south within acceptable intervals. It is suggested that C. tarsalis mosquitoes infected with WEE virus are carried on the wind from Texas on the Gulf of Mexico, where they continue to breed during the northern winter months, to northern Texas and Oklahoma in the spring. In May, June and July C. tarsalis are carried north on southerly winds from these states through Kansas and Nebraska to North Dakota, Minnesota, Wisconsin and Manitoba. Distances of 1250-1350 km are traversed in 18-24 h at heights up to 1.5 km with temperatures greater than or equal to 13 degrees C. Landing takes place where the warm southerly winds meet cold fronts associated with rain. Convergence leads to concentration of C. tarsalis and determines where outbreaks occur. It is possible that return of new generations of C. tarsalis to the south may occur later in the year. The development of an epidemic of WEE in the northern states and provinces would appear to depend on (i) suitable trajectories from the south in June and July with temperatures greater than or equal to 13 degrees C meeting cold fronts with rain, (ii) sufficient C. tarsalis infected with WEE virus at source, carried on the wind and locally, (iii) C. tarsalis biting horses and man, (iv) maintenance of local mosquito populations in August and (v) susceptible hosts (birds) at source and susceptible hosts (horses and man) locally. Possible methods of prediction involving determination of trajectories, identification of C. tarsalis blood meals, measuring seroconversion in calves are discussed in addition to the methods already in use. PMID- 2905670 TI - Food poisoning in hospitals in Scotland, 1978-87. AB - During the 10-year period 1978-87 there were 48 outbreaks of food poisoning in Scottish hospitals affecting a total of 2287 persons of whom 12 died. This compared with 50 outbreaks during the previous 5 years (1973-77) when over 1500 persons and 7 deaths were recorded. Although the incidence of outbreaks has decreased the average number of persons affected in outbreaks has increased. A marked reduction was seen in the incidence of outbreaks due to Clostridium perfringens, in contrast to foodborne salmonellosis which remains a problem. Thirty-four hospitals, of which 10 reported two or more outbreaks, were involved. The type of hospitals most frequently affected were general (14), psychiatric (13), geriatric (9) and hospitals for the mentally subnormal (7). Meat, including poultry meat, was incriminated in over 90% of outbreaks where a food vehicle was identified. In modern or re-equipped kitchens cooking in advance with subsequent reheating is being progressively discontinued as more food is being cooked on the day of consumption, a practice which may readily explain the decreasing incidence of outbreaks due to Cl. perfringens. Bacterial cross-contamination from poultry meat and other raw foods, compounded by inadequate temperature control, however, continues to be a problem in some hospitals. It is too early as yet to determine whether the removal of Crown immunity will have any effect on the future incidence of hospital 'food poisoning'. PMID- 2905671 TI - Peroxisomes in pigment epithelium and Muller cells of amphibian retina possess D amino acid oxidase as well as catalase. AB - In this paper we identify peroxisomes in Muller cells and retinal pigment epithelial cells of Rana pipiens and Xenopus laevis by virtue of their content of cytochemically stainable catalase. These organelles have the form of an extensive, branched system of tubules in the retinal pigment epithelium and appear as discrete ovoid structures in the Muller cells. In both the pigment epithelium and the Muller cells a second peroxisomal enzyme, D-amino acid oxidase, can be detected in the same structures as catalase by means of a cerium based cytochemical staining procedure. This oxidase is active only against nonpolar and polar, uncharged D-amino acids. PMID- 2905672 TI - An immunocytochemical comparison of Muller cells and astrocytes in the cat retina. AB - Immunocytochemical localization, at the light and electron microscopic levels, of five different known glial proteins was used to compare Muller cells with astrocytes in the adult cat retina. Retina from two different areas of the eye was examined. A region of retina on the border of the optic nerve was used because of its large population of astrocytes, and a region away from the optic nerve was used to examine Muller cells (astrocytes are sparse in this region). Antibodies to cellular retinaldehyde binding protein and glutamine synthetase labeled the Muller cells but not the astrocytes, while labeling with anti carbonic anhydrase C, anti-alpha crystallin and anti-glial fibrillary acidic protein was found in both Muller cells and astrocytes. PMID- 2905673 TI - An immunocytochemical study of cat retinal Muller cells in culture. AB - Muller cells, the specialized radial glia found in vertebrate retinas, were enzymatically dissociated from adult cat retinas and grown in culture. The cells were processed for immunofluorescence microscopy at times ranging from 4 hr to 3 months in culture. Labeling with antibodies specific to glial fibrillary acidic protein, cellular retinaldehyde binding protein, glutamine synthetase, carbonic anhydrase C and alpha crystallin, all proteins known to be found in Muller cells, was detected in the cultured cells. Immunoblot analysis of the cultured cells showed single protein bands corresponding to the appropriate molecular weights of the antigens. PMID- 2905675 TI - [Effect of the tripeptide melanostatin on the electrical activity of surviving slices of the olfactory cortex in the rat brain]. AB - The effects of melanostatin (MST 10(-5) M) on transmission in the lateral olfactory tract--superficial pyramidal neurons synapses, were investigated in slices of the rat olfactory cortex. Within 3-6 min after MST addition, the EPSP amplitudes were depressed and then increased (within 6-9 to 30 min); spikes and IPSPs appeared during the latter period. The recovery of the FPs to control values at washing was slow (40-60 min). Possible mechanisms of the MST long-term excitatory effect on neural elements of the slices, are discussed. PMID- 2905674 TI - Differential distribution of biogenic amines in the hypoglossal nucleus of the rat. AB - The distribution of biogenic amines in the rat hypoglossal nucleus (nXII) was investigated with immunocytochemical methods using antibodies to tyrosine hydroxylase (TH) as a marker for catecholamines, and to 5-hydroxytryptamine (5 HT), the principal indoleamine, at the light microscopic level. TH and 5-HT immunoreactivity were found throughout all regions of nXII. Although the innervations overlapped, clearly different patterns of distribution were observed. TH immunoreactivity was localized primarily in the ventromedial quadrant of the caudal half of nXII and appeared largely as perisomatic-like profiles. In contrast, 5-HT immunoreactivity was greatest dorsally along the caudal half of nXII, although secondary foci of staining were evident ventrolaterally and, to a lesser extent, ventromedially. A perisomatic-like pattern of termination was observed for 5-HT in both dorsal and ventral regions of nXII. Since ventral and dorsal districts of nXII contain motoneurons that innervate protrusor and retrusor tongue muscles, respectively, we propose that the overlapping, yet differential distributions of catecholamines and indoleamines are important in controlling the relationships between functionally related groups of nXII motoneurons. These findings are discussed in relation to oro-lingual motor dysfunction. PMID- 2905676 TI - [Dynamic changes in the heart beat frequency of rabbits to auditory and nociceptive signals against the background of neuroleptic action]. AB - Aminazine and haloperidol exerted different effects upon spontaneous heart rate and the reactivity of cardiovascular system in curarized rabbits during habituation to nociceptive and sound signals: aminazine (8-10 mg/kg) increased the heart rate by 8-12% and completely suppressed the reactivity, whereas haloperidol (0.5-1.7 mg/kg) decreased the heart rate by 5.0-8.5% and considerably enhanced the reactivity to sound and nociceptive signals, prolonging the habituation duration. The biphasic response of the rabbit heart rate reveals a working mechanism of the baroreflex control over emotionally significant and stressful effects. PMID- 2905678 TI - Commonly prescribed drugs. PMID- 2905677 TI - [The alpha-adrenergic sensitivity of smooth muscle following sympathectomy]. AB - The effect of sympathetic nerve stimulation on postsynaptic alpha-adrenoceptors of cat's smooth muscle nictitating membrane was studied. L-noradrenaline, adrenaline, phenylephrine and clonidine caused a concentration-dependent contraction. In denervated tissue, the concentration-response curve for clonidine mainly shifted to the left in comparison with the control; in contrast to the innervated smooth muscle, there were no reliable differences between the constant dissociation Ka and KB for alpha 1- and alpha 2-selective and nonselective adrenomimetics and adrenoblockaders. The data obtained suggest alteration of pharmacological characteristics of smooth muscle alpha-adrenoceptors after interruption of the sympathetic nerve. PMID- 2905679 TI - Differential sensitivity of the insulin receptor to proteolysis after beta adrenergic stimulation. AB - The cellular mechanism by which the specific binding of [125I]insulin to intact rat adipocytes is inhibited by isoproterenol has been studied. By exposing control and isoproterenol-treated cells to trypsin (0-150 micrograms/ml for 20 min at 4 degrees C) and measuring the intact insulin receptor pool following detergent solubilization, a differential sensitivity to proteolysis of the cell membrane receptor was observed. At low trypsin concentration (less than 30 micrograms/ml), approximately 40% of the specific insulin binding in isoproterenol-treated cells was insensitive to proteolysis as compared to control cells. At higher levels of trypsin (50-150 micrograms/ml) both groups displayed similar levels of trypsin-insensitive receptors which, at the highest trypsin concentration, accounted for 10% of the total receptors in intact cells. Detergent-solubilized receptors from isoproterenol-treated cells, on the other hand, exhibited the same sensitivity to trypsin proteolysis as solubilized receptors from control cells. The time course of the onset and reversal of the isoproterenol-induced binding alteration in intact adipocytes has been analyzed by mild trypsinization (20 micrograms/ml). Results indicated that insulin receptors resistant to trypsin under these conditions mediated the decreased surface binding and were re-expressed on the cell surface upon removal of isoproterenol. Experiments in which adipocytes were fractionated into plasma membrane and Golgi-enriched fractions indicated that the loss of surface insulin binding was not accompanied by a decrease in the proportion of receptors in the adipocyte plasma membrane.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2905680 TI - [Metabolic and functional basis of correlations between the levels of free neuroactive amino acids and cerebrospinal fluid in patients with epilepsy]. PMID- 2905681 TI - [Anomaloscopy as a method of evaluation of fatigue during work]. PMID- 2905682 TI - [Periarteritis nodosa complicated by intrapancreatic vascular rupture]. AB - Clinical pancreatic manifestations are unusual in polyarteritis nodosa. A case of intrapancreatic hemorrhage due to vascular rupture occurring during the course of histologically proven polyarteritis nodosa is described. The patient presented with massive hemoperitoneum requiring emergency laparotomy. Splenopancreatectomy was performed to control bleeding. Steroid therapy was continued during the postoperative course, with favorable outcome. The mechanism of vascular rupture is not clear, but is probably related to focal arteritis with consequent infarction. No ruptured microaneurysm was found in this case. PMID- 2905683 TI - The influence of atenolol and prazosin on serum lipids and atherosclerosis in minipigs fed a hyperlipidemic diet. AB - 1. The effect of the adrenergic blockers prazosin and atenolol were tested in hypercholesterolemic Gottingen minipigs. 2. After 1 yr there was a significant reduction of plasma triglycerides and total cholesterol in the medicated animals as compared to untreated ones. 3. No significant difference in atherosclerotic lesions was observed. PMID- 2905684 TI - The ubiquitous octamer-binding protein Oct-1 contains a POU domain with a homeo box subdomain. AB - The octamer motif ATGCAAAT is recognized indistinguishably by two mammalian transcription factors: one that is expressed ubiquitously and referred to here as Oct-1, and another, Oct-2, that is expressed in lymphoid cells. We report the cDNA cloning of the human oct-1 gene, which encodes Oct-1, by screening lambda gt11 recombinant phage in situ for octamer motif-specific DNA binding. One lambda gt11 recombinant expressed a beta-galactosidase-octamer-binding fusion protein with a DNA-binding specificity indistinguishable from human HeLa cell Oct-1 protein. As expected for a ubiquitously expressed protein, Oct-1 mRNA is expressed in all five human and two mouse cell lines tested. Polyclonal rabbit antiserum raised against the beta-galactosidase fusion protein shows that the DNA binding domains of Oct-1 and Oct-2 proteins are related antigenically. Deletion analysis of the 743-amino-acid-long oct-1 open reading frame shows that the DNA binding activity lies within a central highly charged domain of 160 amino acids. Comparison of the Oct-1 and Oct-2 sequences reveals that this domain is nearly identical between the two proteins. Highly similar domains are also present in the pituitary-specific transcription factor Pit-1 and the Caenorhabditis elegans unc-86 cell lineage gene product (see Herr et al. 1988). Within this shared POU (Pit-1, Oct-1 and Oct-2, unc-86) domain (pronounced 'pow') lie two subdomains: a POU-related homeo box and a POU-specific box. The Oct-1 protein is unique among the POU-related proteins and other homeo box proteins because it is expressed ubiquitously. PMID- 2905685 TI - Control elements of the P2 promoter of the Antennapedia gene. AB - Antennapedia (Antp), a homeotic gene of Drosophila required for proper differentiation of the thorax of the fly, is expressed in complex spatial patterns during development. The gene is greater than 100 kb long and has two independently regulated promoters. To characterize cis-acting regulatory elements responsible for the expression pattern, fusions of the Antp promoter 2 cap site and upstream sequences to an Adh-lacZ gene were introduced into flies. A 10-kb sequence directs beta-galactosidase production in a pattern that closely resembles the endogenous P2 pattern. Transcription from the 10-kb fusions is regulated by three genes that regulate Antp transcription. Control elements, including a target of action of homeo-domain-containing proteins, were mapped by deleting parts of the 10-kb sequence. PMID- 2905686 TI - A mouse gene homologous to the Drosophila gene caudal is expressed in epithelial cells from the embryonic intestine. AB - A mouse gene, Cdx-1, was isolated from an embryonic cDNA library using a Drosophila caudal gene probe. The deduced amino acid sequence of Cdx-1 contains conserved sequence domains along the entire gene, as well as a highly conserved caudal-type homeo box. A structural comparison suggests a common ancestral origin of mouse Cdx-1 and Drosophila caudal. The expression of Cdx-1 during embryogenesis was analyzed by Northern blotting and in situ hybridization. Cdx-1 specific transcripts are localized in the epithelial lining of the intestines beginning at 14 days' gestation. The expression of Cdx-1 in the intestine continues into adulthood, but cannot be detected in any other tissues. The Cdx-1 gene is the first homeo-box-containing gene expressed in cells derived from the embryonic endoderm. PMID- 2905687 TI - Molecular genetics of the apolipoprotein B gene in pigs in relation to atherosclerosis. AB - Immunologically defined alleles of the pig apolipoprotein B (ApoB) locus (apoB) are correlated with different blood cholesterol levels and predisposition towards premature coronary heart disease. We show here that these alleles are associated with differences in the apoB gene by identifying six restriction fragment length polymorphisms at the pig apoB locus. We have sequenced a 2.4-kb fragment encompassing exons 11 through 14 of one allele, and 7.1 kb from the 3' one-third of exon 26 to about 1 kb past the last exon from another allele. The decoded amino acids of the pig and human ApoB proteins are identical at 70% of these positions. One region close to the C-terminus of the protein is surprisingly different in pigs and humans (57% identity) but the C-terminal region is relatively well conserved (74% identity). Neither of the two putative low-density lipoprotein (LDL) receptor-binding sites is completely conserved in pigs and humans, but identical stretches of amino acids occur near these sites more frequently than in the other sequenced regions. We compare the nucleotide sequences of the region encompassing the putative LDL receptor-binding sites from four pig alleles, including one implicated directly in atherosclerosis. None of the differences appears to account for the hypercholesterolemic phenotype. We conclude that significant differences in the physiology of LDL particles result from changes outside the putative receptor-binding region. PMID- 2905688 TI - A variation in the structure of the protein-coding region of the human p53 gene. AB - An extensive analysis of genomic DNA preparations from a number of normal and malignant tissues revealed BglII site polymorphism of the human p53 gene. Approximately 10% of p53 gene alleles were found to contain an additional BglII site localized in a region of intron I. This allelic form of p53 gene was also responsible for p53 protein having altered electrophoretic mobility. Molecular cloning and sequencing of both the alleles of p53 gene revealed a base-pair change in codon 72 causing arginine----proline substitution in the allele with the additional BglII site. Both variants of the p53 gene may occur in homozygous state and are therefore functional. PMID- 2905689 TI - Polyadenylation of histone H3 and H4 mRNAs in dicotyledonous plants. AB - The histone H3 and H4 genes are shown to be expressed in both Arabidopsis plantlets and transitory multicellular suspension. The 5'- and 3'-ends of the H4 mRNAs have been localized on two H4 genes previously sequenced, H4A748 and H4A777. S1-nuclease mapping and reverse-transcriptase-primer-elongation experiments revealed the existence of two start points for transcription, located 31 and 37 nucleotides downstream from the TATA-box. The 3'-end of the mRNA corresponding to H4A748 was localized at 177 nt after the stop codon. The other gene, H4A777, most probably is not expressed. In addition to a long 3' untranslated region, the H4 mRNA was shown to be polyadenylated in both plantlets and cell-suspension. This observation was extended to the H3 mRNAs of Arabidopsis and of two other dicots, tobacco and sunflower. Previous results on maize H3 and H4 mRNAs suggest that polyadenylation is a common feature for histone mRNAs in higher plants. PMID- 2905690 TI - Prevention of ulcer relapse: rationale. PMID- 2905691 TI - Reduced hypothalamic somatostatin and neuropeptide Y concentrations in the spontaneously-diabetic Chinese hamster. AB - Hypothalamic concentrations of six regulatory peptides having central effects on appetite and/or glucoregulation were measured by radioimmunoassay in spontaneously-diabetic Chinese hamsters and in age- and sex-matched non-diabetic control animals. In the diabetic hamsters, hypothalamic concentrations of somatostatin and neuropeptide Y were significantly reduced by 25-30% below controls. None of the other four peptides examined (bombesin, galanin, neurotensin and vasoactive intestinal peptide) differed significantly between the two groups. Disturbances in neuropeptide Y (the most potent central appetite stimulant yet discovered) and in somatostatin could be related to hyperphagia, an early and possibly primary abnormality of the diabetic syndrome in the Chinese hamster. PMID- 2905692 TI - The course and treatment of schizophrenia in later life. PMID- 2905693 TI - Pathogenesis of urinary tract infections--amoxicillin induces genital Escherichia coli colonization. AB - The aim of this study was to examine whether a vaginal Escherichia coli colonization, mimicking the one seen in UTI-prone females, could be induced by amoxicillin administration. In adult cynomolgus monkeys, who carry the alpha-Gal 1-4-beta-Gal receptor for P-fimbriae, we have investigated the ability of a clinical isolate of P-fimbriated E. coli to colonize the mucous membranes of the genital tract. When the vagina was washed with a suspension of the P-fimbriated strain, a persistent colonization was obtained in only 17% (4/24) of the experiments. When such colonization attempts were performed during vaginal amoxicillin administration, a persistent and heavy colonization of the vagina occurred in 5/5 attempts. The findings do not contradict our hypothesis that antibiotics given to UTI-prone females may facilitate the establishment of the abnormal colonization of the genital tract. PMID- 2905694 TI - Fecal colonization with P-fimbriated Escherichia coli as a predictor of acute pyelonephritis in infancy--a prospective study. AB - The importance of fecal colonization with P-fimbriated Escherichia coli for the later development of pyelonephritis was studied among infants before the age of 11 months. In contrast to previous studies, the fecal colonization with a P fimbriated E. coli strain did not increase the incidence of acute pyelonephritis. PMID- 2905695 TI - Investigations of arterio-venous anastomoses in the spermatic cords and blood supply, oxygen consumption and testosterone production of scrotal and abdominal testes in the pig. AB - This study has investigated blood flow from the testicular artery to the pampiniform plexus in the spermatic cord of pigs. Testosterone levels, oxygen tension and the degree of acidity were measured in arterial and venous blood vessels of scrotally and abdominally located testes. Haemoglobin oxygen saturation was derived from the oxygen dissociation curve. Blood flow to abdominal and scrotal testes and epididymides was measured using the radioactive microsphere technique. Average blood flow to the scrotal testes and epididymides was 21 and 8 ml/min, respectively, in normal pigs. In unilaterally cryptorchid pigs average blood flow to the scrotal testis and epididymis was 23 and 6 ml/min, respectively, and to the abdominal testis and epididymis 4.2 and 1 ml/min. In pigs with bilateral scrotal testes oxygen consumption was 16 mumol O2/min/100 g. In unilaterally cryptorchid pigs oxygen consumption by the scrotal testis was 18 mumol O2/min/100 g, compared with 10 mumol O2/min/100 g by cryptorchid testes. From the percentage oxygen saturation in the various blood vessels it was calculated that 29-42% of testicular arterial blood was flowing through arteriovenous anastomoses between the testicular artery and the pampiniform plexus in the spermatic cord, thus bypassing the capillary net of the abdominal testes of unilaterally and bilaterally cryptorchid pigs. These results were supported by the testosterone measurements. In the spermatic cord of scrotal testes no blood bypassed the capillary net of the testes. PMID- 2905696 TI - Sexual side-effects of psychiatric drugs. AB - Clinical case reports, clinical series, and a small number of controlled studies provide evidence that many commonly prescribed psychiatric drugs may have untoward effects on sexual function. Both heterocyclic antidepressants and monoamine oxidase inhibitors appear to be associated with ejaculatory impairment. Erectile dysfunction and retarded ejaculation have been associated with neuroleptics. Several benzodiazepines have been reported to interfere with ejaculation. This information has clear significance for the prescribing physician. PMID- 2905697 TI - Physician/patient relationship prevails. PMID- 2905698 TI - Cochlear implants. PMID- 2905699 TI - Daniel A. Carrion: 1858-1885. PMID- 2905701 TI - One doctor's formula for community outreach. Seizing the moment. PMID- 2905700 TI - The Care Center cares. PMID- 2905702 TI - Illinois medicine: the best we can be. PMID- 2905703 TI - High-performance liquid chromatographic determination of famotidine in urine. PMID- 2905704 TI - Stereoselective analysis of the enantiomers of ethotoin in human serum using chiral stationary phase liquid chromatography and gas chromatography-mass spectrometry. PMID- 2905705 TI - Gas chromatographic method for the determination of cetirizine in plasma. PMID- 2905706 TI - Identification and differentiation of alkylamine antihistamines and their metabolites in urine by computerized gas chromatography-mass spectrometry. AB - A gas chromatographic-mass spectrometric screening procedure is described for the identification and differentiation of the following alkylamine antihistamines and their metabolites in urine: azatadine, benzquinamide, brompheniramine, chlorphenamine, (clofedanol), cyproheptadine, dimetindene, ketotifen, mebhydroline, phenindamine, pheniramine, pyrrobutamine, terfenadine and tolpropamine. After acid hydrolysis of the conjugates, extraction and acetylation, the urine samples were analysed by computerized gas chromatography mass spectrometry. Using ion chromatography with the selective ions m/z 58, 169, 203, 205, 230, 233, 262 and 337, the presence of alkylamine antihistamines and/or their metabolites was indicated. The identity of positive signals in the reconstructed ion chromatograms was confirmed by a visual or computerized comparison of the stored full mass spectra with the reference spectra. The ion chromatograms, reference mass spectra and gas chromatographic retention indices (OV-101) are documented. The procedure presented is integrated in a general screening procedure (general unknown analysis) for several groups of drugs. PMID- 2905707 TI - Trace analysis of explosives by capillary supercritical fluid chromatography with thermal energy analysis detection. PMID- 2905708 TI - Liquid chromatographic determination of halazepam in commercial tablets. PMID- 2905709 TI - The effect of histamine-2 receptor antagonists on tocainide pharmacokinetics. AB - The effects of cimetidine and ranitidine on tocainide pharmacokinetics were assessed in seven healthy subjects, using a randomized, double-blind, placebo controlled, cross-over study design. After a 400-mg oral dose of tocainide, the area under the concentration-time curve decreased from (mean +/- SD) 31.64 +/- 14.16 micrograms.hr/mL during placebo, to 23.10 +/- 7.33 micrograms.hr/mL during cimetidine (P less than .05). Similarly, the peak tocainide concentrations were 2.81 +/- 0.89 micrograms/mL and 1.70 +/- 0.44 micrograms/mL with placebo and cimetidine, respectively (P less than .05). There was no change in the above parameters between ranitidine and placebo. The terminal half-life and renal clearance of tocainide were not altered by either H2-receptor antagonists, compared with placebo. However, the total amount of tocainide excreted unchanged in the urine, decreased from 159.8 +/- 14.7 mg with placebo to 136.8 +/- 26.8 mg with cimetidine (P less than .05), whereas there was no change with ranitidine. These data indicate that cimetidine, but not ranitidine, causes a decrease in the bioavailability of tocainide and that neither agent alters the apparent elimination rate of tocainide. PMID- 2905710 TI - Efficacy of esmolol in the treatment and transfer of patients with supraventricular tachyarrhythmias to alternate oral antiarrhythmic agents. AB - The efficacy and safety of esmolol, a titratable intravenous beta-adrenergic blocking agent with a short elimination half-life (t 1/2 = 9.0 min) was evaluated in a multicenter open-label study for the treatment of supraventricular tachyarrhythmias (heart rate greater than 100 bpm). The study also investigated the feasibility of transferring patients from esmolol to alternate oral antiarrhythmic agents without loss of therapeutic response. Of the 113 patients studied, 95 (84%) achieved therapeutic response (reduction in heart rate of 15% or more or conversion to sinus rhythm). Most of these patients (93%) achieved the therapeutic response at esmolol doses of 200 micrograms/kg/min or lower. Transfer from esmolol to an oral antiarrhythmic agent(s) was studied in 76 patients. Alternate antiarrhythmic agents used in this study were digoxin (N = 25), propranolol (N = 21), verapamil (N = 10), metoprolol (N = 11), quinidine (N = 2), and a combination of two antiarrhythmic agents (N = 7). Sixty-seven (88%) patients were successfully transferred to oral antiarrhythmic agents without loss of the therapeutic response obtained with esmolol. The most frequent adverse effect observed during the study was hypotension, which resolved quickly (16 +/- 14 min) either by decreasing the dose or by discontinuation of esmolol infusion. This study supports previous observations concerning the safety and efficacy of esmolol in the treatment of supraventricular tachyarrhythmias. Furthermore, it demonstrates that the majority of patients successfully treated with esmolol can be safely and effectively transferred to oral therapy with alternate antiarrhythmic agents. PMID- 2905711 TI - Effect of cetamolol on epinephrine-induced hypokalemia. AB - The effect of cetamolol (an investigational cardioselective beta blocker with intrinsic sympathomimetic activity) on the hypokalemic response to epinephrine infusions in normal subjects was evaluated and compared with placebo and two other beta-adrenergic blocking drugs. After two daily doses of cetamolol 15 mg, atenolol (a cardioselective beta blocker) 50 mg; a long-acting propranolol preparation (a nonselective beta blocker) 80 mg; or placebo, 12 men (mean age, 26.7 years) were infused with epinephrine. The resulting average plasma epinephrine level was 1123 pg/mL, whereas average baseline serum potassium levels for the four treatment groups ranged from 3.94 to 4.07 mEq/L. Epinephrine-induced hypokalemia occurred in the placebo group (maximum potassium decrease of 1.00 mEq/L) and in the atenolol group (maximum potassium decrease of 0.59 mEq/L); potassium levels did not decrease but rose slightly in subjects receiving cetamolol or propranolol. Subjects treated with placebo or atenolol also demonstrated statistically significant prolongation of the QTc interval (0.039 seconds with placebo; 0.023 seconds with atenolol) and frequently developed T wave flattening and U-wave appearance. After pretreatment with cetamolol or propranolol, however, the QTc interval was unaffected, T-wave abnormalities did not occur, and U waves appeared only rarely. The results of this study indicate that cetamolol blocks epinephrine-induced hypokalemia and associated electrocardiographic changes. PMID- 2905712 TI - Antibiotic resistance of coagulase-negative staphylococci in an orthopaedic department. AB - Coagulase-negative staphylococci (CNS) were cultured from the anterior nares of surgeons, theatre and ward staff, and from patients before and 2 weeks after a total hip replacement. The CNS found in ward staff were more resistant to antibiotics than those in surgeons and theatre staff. Methicillin resistance of CNS in patients increased from 4 to 31% following surgery. Gentamicin-resistant CNS were only found postoperatively, in 20% of patients, in most of whom gentamicin-loaded acrylic bone cement was used. PMID- 2905713 TI - Safety devices to prevent airborne infection from clinical suction apparatus. AB - Infection related to clinical suction apparatus has been widely recognized. Safety systems available at present include devices to prevent overflow from collecting vessels and in-line air filters. The relative efficiency of these devices for the containment of aerosols generated within the collecting vessel has been evaluated. Although of increased resistance, filter capsules of 0.3 micron pore size prevented the passage of test aerosols for longer periods than the widely used 8-micron fibre filter tubes. Filter life can be prolonged by preventing overflow from collecting vessels and protecting against the passage of foam and froth. PMID- 2905714 TI - Infection control in a skilled nursing facility: a 6-year survey. AB - In 1981 an infection control programme was started in a 320-bed skilled nursing facility in The Netherlands. The programme consisted of recording the antimicrobial drugs prescribed and the site of infection, culture of urine from patients admitted from hospital and from residents with suspected symptomatic urinary tract infection, restriction of long-term indwelling urethral catheterization and restricted use of antimicrobial drugs. At a weekly staff meeting, these data were reviewed. As a result of the programme, the number of treatments for urinary tract infections decreased by 74% between 1981 and 1986, and the number of courses for recurrent urinary tract infections decreased from 18 to 6% of the total number given. The patients who did not require antimicrobial therapy increased from 51% in 1981 to 70% in 1986. PMID- 2905715 TI - A microbiological study of absorbent pads. AB - A study was carried out of the microbial content of three types of incontinence underpads and a clinical absorbent protection pad. Coagulase-negative staphylococci and Bacillus spp. were isolated from unused samples of all makes of pad examined. Clostridium spp., including C. tetani and C. perfringens, were isolated from a proportion of pads containing re-cycled waste material. We recommend that incontinence underpads are used solely for the purpose for which they were marketed, namely, the containment of excreta. PMID- 2905716 TI - Single dose mezlocillin versus three dose cefuroxime plus metronidazole for prophylaxis in large bowel surgery. PMID- 2905717 TI - Acute hepatitis B following gynaecological surgery. PMID- 2905718 TI - Pseudobacteraemia again. PMID- 2905719 TI - Chromosomally-encoded aminoglycoside resistance in methicillin-resistant Staphylococcus aureus. PMID- 2905720 TI - Endemic occurrence of Acinetobacter calcoaceticus biovar anitratus in an intensive care unit. PMID- 2905721 TI - A placebo-controlled trial of the effect of two preoperative baths or showers with chlorhexidine detergent on postoperative wound infection rates. PMID- 2905722 TI - The importation of multiple-resistant bacterial pathogens into British hospitals. PMID- 2905723 TI - Clostridial hand-carriage and neonatal necrotising enterocolitis. PMID- 2905724 TI - Antibiotic prophylaxis in transurethral resection of the prostate with reference to the influence of preoperative catheterization. AB - The value of prophylactic antibiotics in transurethral resection of the prostate (TURP) remains controversial. We have conducted a prospective study in which 308 patients undergoing TURP have been randomized to receive no antibiotic cover (n = 150) or 36 h perioperative cover with temocillin. In 62 patients the urine was found to be infected at the time of operation. In these patients the incidence of postoperative urinary-tract infection (UTI) was 33% in the group who received temocillin, and 87% in the control group (P less than 0.001). In patients with sterile urine at operation (n = 235), the incidence of postoperative UTI was 13% in the temocillin group compared with 24% in the control group (P less than 0.05). Gram-positive organisms were mainly responsible for infection which occurred in patients who had received temocillin. A high incidence of postoperative UTI occurred in patients who had required preoperative catheterization despite the fact that their preoperative urine specimen was sterile. We conclude, (i) prophylactic antibiotics are of benefit in patients undergoing TURP, (ii) the antibiotic administered should be active against both gram-positive and gram-negative organisms, (iii) patients with an indwelling catheter should be considered at a higher risk of infection whether or not organisms are cultured from their preoperative urine specimen. PMID- 2905725 TI - Serological studies on health care workers caring for patients with human immunodeficiency virus. AB - Between 1982 and July 1987, more than 1200 patients attending St Stephen's Hospital were found to be HIV antibody positive. Four hundred were inpatients and most of the outpatients attended the sexually transmitted disease clinic. Two hundred and twenty-one patients had AIDS, 480 HIV-related disorders and 500 were asymptomatic. Most inpatients had invasive procedures within the operating theatres and there were 25 postmortems. Four hundred and five antibody tests from 220 health care workers from the STD clinic, operating theatres, isolation ward, intensive care unit and clinical laboratories were voluntarily tested for HIV antibody by an ELISA screening method. All were negative, except one male nurse who had other risk factors. Twenty-nine staff suffered needlestick injury with blood of HIV antibody positive patients; none has developed serological evidence of HIV infection. PMID- 2905726 TI - Methicillin-resistant Staphylococcus aureus bacteraemia in Hong Kong. AB - In the first 22 months of operation at the Prince of Wales Hospital, 26 (46%) of 56 hospital-acquired Staphylococcus aureus bacteraemias were due to methicillin resistant organisms (MRSA). There were 10 plasmid profiles amongst 24 of the MRSA strains analysed. MRSA bacteraemias were first seen in the hospital 1 year after opening when the isolation rate of MRSA from all sites had risen to about 1% of patient admissions. During the last 3 months of the study period, 17 out of 18 S. aureus bacteraemias were due to methicillin-resistant strains. Patients with MRSA bacteraemia were significantly more likely than those with methicillin-sensitive S. aureus bacteraemia to have had a severe underlying disease, a poor clinical prognosis, prolonged hospitalization, and prior antimicrobial therapy, especially with aminoglycosides. They also had a significantly longer hospital stay after infection, a significantly higher cost of antimicrobial therapy and a higher mortality rate. The lower mortality rate in MRSA patients treated with vancomycin (18%) compared with those treated with other antimicrobials (40%) confirms that, at present, vancomycin is the treatment of choice for invasive MRSA infections. PMID- 2905727 TI - [An autopsy case of clostridial liver abscess]. PMID- 2905728 TI - [A case of hypothyroidism with marked hypertrophy of external ocular muscles and highly elevated thyroid-stimulating antibody (TSAb)]. PMID- 2905729 TI - [Haplotypes associated with the cystic fibrosis gene (CF)]. AB - The linkage relationships between the cystic fibrosis locus and six marker loci allowed us to build 122 haplotypes bearing the CF gene and to compare them to the 122 normal haplotypes. We obtained 13 different marker haplotypes associated with the CF chromosomes and 22 with the normals in our population. To examine the possibility of a correlation between the clinical and the genetical polymorphism of the disease haplotype analysis was carried out taking in account age at diagnosis, severity of the disease and a particular clinical subgroup such as meconium ileus or pancreatic sufficiency. The results showed that a particular haplotype (121) is predominant in the severe form of the disease. This may have implication in diagnosis and prognosis of the disease. PMID- 2905730 TI - Restriction endonuclease analysis of leukocyte mitochondrial DNA in Leber's optic atrophy. AB - In order to test the hypothesis that Leber's optic atrophy may be caused by mutation of the mitochondrial (mt) genome, restriction fragment length polymorphism in leukocyte mt DNA was studied in 16 patients with Leber's optic atrophy, 28 of their unaffected matrilineal relatives, and 35 normal control subjects. No differences in restriction fragment patterns were observed between affected and unaffected individuals in the same maternal line, and there was no evidence of major deletion of mt DNA in patients. This study provides no positive evidence of mitochondrial inheritance in Leber's optic atrophy but does not exclude it. PMID- 2905731 TI - Conformation-activity relationships of opiate analgesics. AB - Extensive conformational calculations were performed on the potent opiate analgesics etorphine, PET, R30490 and etonitazene to determine all of their many low-energy conformations. The results were used to characterize four possible models for binding of a simple pharmacophore, comprising two phenyl rings plus a protonated nitrogen, to opiate analgesic receptors. These four models may define the necessary three-dimensional features leading to particular opiate actions. The model favoured for mu receptor activity can accommodate a protonated nitrogen, an aromatic ring (which may be substituted with an electronegative group) and a second lipophilic group. These structural features must be presented in a precise three-dimensional arrangement. It appears likely that a hydrophilic substituent in a certain region of the analgesic pharmacophore may also interact with the receptor as a secondary binding group. PMID- 2905732 TI - Potential adverse effects of antihypertensive drugs in the elderly. AB - Antihypertensive therapy is effective in elderly patients, at least in those under 80 years old. Stepped care may still serve as a therapeutic framework which is modified to fit the individual elderly patient, according to the risk: benefit ratio. However, there are no risk-free drugs and no antihypertensive agent is universally effective. The elderly are probably more sensitive than younger patients to the adverse effects of antihypertensive drugs, for various reasons, among which are age- and disease-related changes that can lead to altered pharmacodynamics and pharmacokinetics. Multiple pathology and multiple drug therapy is likely to lead to an increased number of drug-drug and drug-disease interactions in the elderly. The elderly are probably most at risk from side effects that influence the cardiovascular and the central nervous system. PMID- 2905733 TI - What about mosquitoes and saliva? Or, is the human immunodeficiency virus transmitted in other ways? PMID- 2905734 TI - Stability of famotidine in commonly used nutritional infusion fluids. PMID- 2905735 TI - The effects of intracerebroventricular administration of adrenergic agonists and antagonists on adrenaline secretion from the adrenal medulla in stressed conscious rats. AB - The effects of intracerebroventricular (i.c.v.) administration of adrenergic agonists and antagonists on the increase in serum adrenaline (Ad) induced by immobilization stress were examined in unanesthetized, unrestrained rats. The serum Ad of rats showed a significant linear increase as time elapsed after the induction of immobilization stress. This immobilization stress-induced increase was inhibited by the i.c.v. administration of a small amount of noradrenaline (NA) and phenylephrine. Isoproterenol and clonidine failed to inhibit the immobilization stress-induced increase. The inhibition of the immobilization stress-induced increase by i.c.v. administration of NA was antagonized by pretreatment with phentolamine and prazosin, but not by pretreatment with yohimbine and propranolol. These results suggested that NA administered via an i.c.v. route may inhibit the stress-induced increase in adrenomedullary Ad secretion by an action on the central alpha 1-adrenoceptor. PMID- 2905736 TI - British pharmaceutical conference 1988. Science proceedings. 125th meeting, Aberdeen, September 11-17, 1988. Abstracts. PMID- 2905737 TI - [Autonomic dysfunction and effect of long-term administration of beta-receptor blocking agent in mitral valve prolapse]. PMID- 2905738 TI - [Pharmacodynamic tests in patients with mitral valve prolapse]. PMID- 2905739 TI - Prevalence of HIV-1 and HIV-2/HTLV-IV infections in Luanda and Cabinda, Angola. AB - A seroepidemiological study of human immune deficiency virus type 1 (HIV-1) and HIV-2/human T-lymphotropic virus type IV (HIV-2/HTLV-IV) infections was performed in Angola in October 1986. Until then five cases of acquired immune deficiency syndrome (AIDS) had been registered in Angola. During this study, another three cases with clinical AIDS were found and confirmed by HIV-1 serology. A total of 1,215 sera from groups of healthy persons and patients were tested for HIV-1 and HIV-2/HTLV-IV antibodies by enzyme-linked immunosorbent assays (ELISA). Sera positive by ELISA were also tested by Western blot (WB) analysis. In Luanda, the capital, HIV-1 antibodies were demonstrated in 0.4% (2/452) of male blood donors, in 0.3% (1/357) of pregnant women, in 1% (1/100) of tuberculosis patients, in 4% (4/94) of patients at medical wards, and in none of 22 women hospitalized with pelvic infections. In the Cabinda province, 11% (4/38) of postnatal women at a maternity ward were found to be HIV-1 seropositive, but only 2% (1/55) of other hospitalized patients and none of 32 male blood donors or 59 healthy persons in a village on the border to Zaire. Specific antibodies to HIV-2/HTLV-IV were not found in any of the sera. However, 16 out of 17 HIV-1 positive sera cross-reacted with HIV-2/HTLV-IV core proteins by WB. In October 1987, 280 of the blood donors from Luanda were retested for HIV-1 antibodies and one of them was found to have seroconverted during the previous year.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2905740 TI - A randomized placebo-controlled trial of recombinant human interferon alpha 2a in patients with AIDS. Interferon Alpha Study Group. AB - We performed a randomized, double-blind, placebo-controlled trial to assess the tolerance and efficacy of recombinant human interferon alpha 2a (Roferon A) in patients with acquired immunodeficiency syndrome (AIDS) without Kaposi's sarcoma. A total of 67 patients were enrolled in five medical centers from October 1983 through April 1986, and received either placebo, 3 million units, or 36 million units of interferon alpha three times a week for 12 weeks. There were no significant differences in median survival, frequency of development of opportunistic infections, median T4-cell counts, or serum p24 antigen levels during therapy among the three groups. There was a significant increase in weight in the 3-million-unit group compared with 36-million-unit and placebo groups. Adverse reactions were common in the two interferon groups, but did not differ significantly from the placebo group. Neither significant therapeutic benefit nor adverse reaction was demonstrated in this study to be associated with interferon alpha administration. This study underlines the value of randomized, double blind, placebo-controlled studies to address specific issues of drug efficacy and toxicity. PMID- 2905741 TI - IV International Conference on AIDS, June 12, 1988. Keynote address. PMID- 2905742 TI - Patterns of CD4+ cell changes after HIV-1 infection indicate the existence of a codeterminant of AIDS. AB - Successive interval slopes of CD4+ cells each constructed from levels at three consecutive 6 month visits were compared over 3 years of follow-up among 565 persistently HIV-1 antibody-positive, 326 persistently antibody-negative, and 51 seroconverting homosexual men who had at least 500 CD4+ cells/mm3 at baseline and completed the first three 6 month visits. "Change" was defined as a difference between two successive interval slopes. Sixty-two percent of seroconverters meeting these criteria experienced a shift in one or more of their successive CD4+ interval slopes, the majority (56%) from a level slope to a negative slope (decreasing numbers of CD4+ cells), a significantly greater proportion than that observed among seronegatives (30%, p less than 0.0001). Fifty-eight percent of the seropositives maintained level interval slopes over the 3 years of follow-up. The majority (59%) of those men experiencing a shift went from a level to a negative interval slope, a significantly greater proportion than observed among seronegatives (30%, p less than 0.0001). The observed patterns of change in interval slopes are consistent with the laboratory observation that CD4+ cells must be activated to replicate HIV-1. The use of the interval slope strategy provides a method to identify a temporal focal point at which to examine possible codeterminants that trigger the production of HIV-1 and the subsequent decline in CD4+ cells. PMID- 2905743 TI - Predictors of decline in CD4 lymphocytes in a cohort of homosexual men infected with human immunodeficiency virus. AB - Longitudinal data on four visits scheduled at 6 month intervals were available on a cohort of 1,827 homosexual men who were human immunodeficiency virus (HIV) seropositive at entry. To identify predictors of the rate of decline of CD4 T lymphocytes, we used an autoregressive model that relates CD4 counts to predictor variables, while adjusting for previous CD4 counts. Significant predictors of steeper decline of CD4 counts were high CD8 count, low hemoglobin, low platelets, high serum IgA, high cytomegalovirus (CMV) antibody, and low HIV antibody. Using the fitted model, a subject with an initial deficit of 314 CD4 cells (median value of study sample) with respect to seronegative subjects and with average values in all other predictors is estimated to lose approximately 53 cells in a 6 month period (95% C.I. = 45-61 cells). Contrasting this estimate to the one obtained with similar methods in intravenous drug users, it is suggested that a faster rate of decline is present among i.v. drug users. This analysis provides evidence that several covariates in addition to previous number of CD4 counts have significant predictive power for estimating the decline in CD4 counts in HIV seropositive subjects. PMID- 2905744 TI - [Determination of isofloxythepin in biological fluids by high-performance liquid chromatography with fluorometric detection]. PMID- 2905745 TI - Relapse. PMID- 2905746 TI - Assessment scales for tardive dyskinesia. PMID- 2905747 TI - Benzodiazepines: time to withdraw. PMID- 2905748 TI - Phenylketonuria in Greece: 12 years' experience. AB - Screening of 1,042,000 Greek newborns for PKU using the Guthrie test, revealed a mean incidence 1:10,420 for Hyperphenylalaninaemia (1:24,233 classic PKU and 1:18,280 benign variants). The mean Phe concentration of the first sample (3-15 days) was 14.1 mg/dl (6-40) for PKU while, for variants, it was 7.7 mg/dl (4-16). Using 4 mg/dl as the limit under which no repeat test was requested, no case of PKU has been missed. On the whole, 100 newborns with persistent Hphe have been detected: 43 proved to be classical PKU and 57 benign variants. After excluding BH4 deficiency, Phe blood level has been kept below 10 mg/dl in all Hphe babies during the first 2 years of life, irrespective of the type of Hphe. All treated Hphe babies have developed normally. Discrimination between PKU and variants was achieved in the 6-18 months of life with protein loading tests. Treated PKU children had the lowest Phe concentrations during the first year of life (mean 5.1 mg/dl). From then on, a steady yearly increase was observed. Their mean IQ in the Stanford-Binet L-M dropped from 107.2 in the second year to 95.8 in the sixth year. A high negative correlation is not clearly shown, probably due to the small number of cases. PKU clinic (supportive and counselling group therapy) along with individual consultations have proved to be helpful, as has the promotion of diet compliance. The need to individualize each of Hphe before deciding upon ways of treatment is stressed and a protocol to be followed for each Hphe is proposed. PMID- 2905749 TI - Intracellular messengers in the generation and degeneration of hippocampal neuroarchitecture. AB - The actions and interactions of the neurotransmitter glutamate and the intracellular messengers calcium, cyclic AMP, and protein kinase C (PKC) in the regulation of neurite outgrowth and cell survival were examined in hippocampal pyramidal-like neurons in isolated cell culture. Low, subtoxic levels of glutamate (10-100 microM) caused the regression of dendrites but not axons; millimolar levels caused cell death. Calcium ionophore A23187 (50-100 nM) and the PKC activator phorbol-12-myristate-13-acetate (PMA; 10-50 nM) caused the regression of both axons and dendrites, whereas the adenylate cyclase activator forskolin enhanced outgrowth rates in both axons and dendrites. The effects of glutamate, A23187, PMA, and forskolin on outgrowth were mediated locally at the growth cones; dendrites were more sensitive than axons to each of these agents. High levels of A23187 (1 microM) or PMA (100 nM) significantly reduced cell survival. Co2+ and trifluoperazine each significantly reduced glutamate-induced dendritic regression and neurotoxicity suggesting that calcium influx and/or PKC activation mediated glutamate's actions. Fura-2 measurements showed that glutamate caused a rapid rise in intracellular calcium levels; this rise was prevented by Co2+. PMA and forskolin did not alter intracellular calcium levels, nor did these agents affect glutamate-induced calcium rises. Taken together, the results indicate that parallel intracellular messenger pathways that influence neurite outgrowth and cell survival are operative in hippocampal neurons; these messengers may play roles in the formation and modification of neuronal circuitry. PMID- 2905750 TI - The relevance to clinical care of recent research in neurobiology. AB - Progress continues to be made in clarifying neurobiological factors in alcoholism and other chemical dependencies. Research in animal behavioral genetics and human genetics has revealed substantial genetic predispositions for some cases of alcoholism. Studies of neurotransmitters suggest that some alcoholics may have antecedent deficiencies in one or more important neurochemical systems. Cocaine dependence is considered to be related to biphasic change in dopaminergic neurons and receptor systems. Condensation products such as salsolinol, tetrahydropapaveroline, and beta carbolines can alter alcoholic preference and motivate heavy ethanol consumption in animals. However, hypothesized theoretical mechanisms underlying such increased drinking with infusions of condensation products are unclear and may require revision. New pharmacological treatments stemming from advances in neurobiological research have been applied successfully to treatment of withdrawal states, but none have been demonstrated to be appropriate for long-term maintenance of abstinence. PMID- 2905751 TI - [Effects of famotidine on plasma pentazocine concentration in surgical patients]. PMID- 2905752 TI - Renal tubular function in urinary stone disease. PMID- 2905753 TI - [Changes in respiratory function during the postoperative period]. PMID- 2905754 TI - Double pylorus accompanied by gastric ulcer resistant to H2-receptor antagonist- a case report and review of the literature. PMID- 2905756 TI - Limitations of the technique of pressure microinjection of excitatory amino acids for evoking responses from localized regions of the CNS. AB - The aim of this study, performed on anaesthetized cats and rabbits, was to test the assumption that pressure microinjections of excitatory amino acids cause long lasting excitation of neurones located close to the injection site. Unitary action potentials or antidromic field potentials were recorded from respiratory or 'reticular' neurones in the medulla oblongata and from phrenic motoneurones at different distances from the injection site. Injection of 10-150 nl (5-150 nmol) of L-glutamate or DL-homocysteic acid into these areas resulted in complex and widespread neuronal events. Generally, more distant neurones (500-1300 microns) were excited for variable periods of time (3-15 min), while neurones in the vicinity of the injection site (0-500 microns) showed, after a brief period of excitation time, a long-lasting (up to 30 min) decrease in excitability or silencing of discharge, probably due to a depolarizing block and disturbances in the ionic composition of the extracellular space. These findings show that interpretation of physiological responses following such injections should not be based on an assumption of local neuronal excitation. Some recommendations regarding the use of this technique are made. PMID- 2905755 TI - Inhibition of proliferation of human promyelocytic leukaemia HL60 cells by S-D lactoylglutathione in vitro. AB - Human promyelocytic leukaemia HL60 cells were incubated with the glyoxalase intermediate S-D-lactoylglutathione in culture. The effects on cell proliferation, maturation, viability and cell cycle were investigated. When HL60 cells (5 x 10(4)/ml) were incubated with 50-500 microM S-D-lactoylglutathione for two days, the rate of cell proliferation was decreased. This effect was maximal at 500 microM S-D-lactoylglutathione where the cell proliferation rate was only 16% of control levels. There was a concomitant decrease in cell viability but little differentiation. During the first day of treatment, there was a significant decrease in the percentage of cells in the G2-M phase of the cell cycle with a concomitant increase in the G0-G1 phase. In contrast, when HL60 cells were incubated with 1.0-1.5 mM S-D-lactoylglutathione, the inhibition of cell proliferation was progressively lifted, with a concomitant increase in the percentage of differentiated cells (27% differentiation with 1.5 mM S-D lactoylglutathione). The activities of glyoxalase II and gamma-glutamyl transpeptidase were increased in these cells. S-D-Lactoylglutathione slowly entered the HL60 cells and was consumed over the period when changes in cell cycle distribution, growth arrest and decrease in cell viability were observed. The mechanism of inhibition of proliferation of HL60 promyelocytes by S-D lactoylglutathione is unknown but it may be related to the ability of S-D lactoylglutathione to stimulate the assembly of microtubules. PMID- 2905757 TI - [Sulfasalazine-induced megaloblastic anemia in rheumatoid arthritis]. PMID- 2905758 TI - Modifications of serum hepatic enzymes in thyrotoxic patients with and without treatment. PMID- 2905759 TI - Haematological adverse effects of histamine H2-receptor antagonists. AB - Histamine H2-receptor antagonists are widely used in the treatment of gastrointestinal diseases related to gastric acid hypersecretion. Cimetidine was introduced into medical practice in 1976 and ranitidine, famotidine and nizatidine in 1981, 1985 and 1987, respectively. Haematological adverse effects are relatively uncommon and most have been reported in cases of cimetidine administration. These adverse effects are reviewed under 4 main headings: (a) blood cytopenias and leucocytosis; (b) coagulation disorders related to drug interactions with oral anticoagulants; (c) reduction of dietary iron absorption; and (d) reduction of dietary cobalamin absorption. 85 reported cases of blood cytopenias attributed to these drugs are reviewed, of which 75 (88%) were associated with cimetidine therapy. In postmarketing surveillance studies, the incidence of cimetidine-associated blood cytopenia has been evaluated at about 2.3 per 100,000 patients. Neutropenia and agranulocytosis are by far the most frequently encountered. Whatever the drug or the type of cytopenia, this adverse effect is almost always rapidly reversible when treatment is stopped. Moreover, in several cases other factors such as underlying diseases or additional drugs could have been responsible, at least partly, for the cytopenia. The pathophysiological basis of these adverse effects remains poorly explained. Various mechanisms have been proposed, which in some cases are probably associated: (a) direct toxicity for haemopoietic stem cells; (b) drug-induced immune reactions leading to blood or bone marrow cell damage, and (c) drug interactions, with increased and prolonged action of potentially haematotoxic drugs. Mechanisms (a) and (c) appear to be of particular clinical importance in cases of impaired renal elimination of H2-receptor antagonists. Cimetidine and probably to a lesser extent ranitidine potentiate the action of oral anticoagulants of both coumarin and indanedione structure. This may result in haemorrhagic complications. Such action is a consequence of the reduced hepatic metabolism of oral anticoagulants through a dose-dependent, reversible inhibition of cytochrome P450. Malabsorption of dietary iron and cobalamin appears to result from inhibition of gastric secretion by the H2-receptor antagonists. This is of no clinical importance in short term treatment, but long term use of H2-receptor antagonists may theoretically contribute to the occurrence of iron or cobalamin deficiency anaemia. PMID- 2905760 TI - Bacterial genotoxicity of nitrosated famotidine. AB - Famotidine, a histamine H2-receptor antagonist, was devoid of mutagenic activity in seven his- Salmonella typhimurium strains (TA1535, TA1537, TA1538, TA97, TA98, TA100 and TA102) and was equitoxic in repair-proficient (WP2) and repair deficient (WP2uvrA, WP67, CM561, CM571, WP100 and CM871) Escherichia coli strains, both in the presence and in the absence of S9 mix containing liver S9 fractions from Aroclor-treated rats. However, after a short pre-incubation step with nitrite in an acidic environment, the drug increased, by a direct mechanism, the number of his+ revertants in Salmonella strains TA100, TA102 and TA97 (a decrease of mutagenicity being conversely observed in TA1535) and of trp+ revertants in E. coli strains WP2uvrA and WP67. Moreover, it enhanced the induction of non-reparable DNA damage in E. coli strains simultaneously lacking the uvrA-dependent excision repair and the lexA post-replication repair pathways. The mutagenicity of acidified nitrite-famotidine mixtures was related to doses of both precursors, with a maximum production of mutagenic derivatives in a slight molar excess of nitrite. The optimal pH of the nitrosation reaction (2.0) was intermediate between the one required for cimetidine (1.5) and ranitidine (2.5). Potency of famotidine as a precursor of mutagenic derivatives was considerably lower than the one of the other two H2 blockers. The nitrosation products of all three drugs mainly induced base-pair substitutions in Salmonella DNA, to a greater extent at sites containing G.C base pairs (strain TA100) in the case of famotidine and cimetidine, and at sites containing A.T base pairs (TA102) in the case of ranitidine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2905761 TI - Measurement of active constitutive L-pyrrolidonyl-peptidase from the genera Streptococcus and Enterococcus. AB - In the family Streptococceae the ability to measure L-pyrrolidonyl-peptidase is limited to Lancefield group D Enterococcus and group A Streptococcus pyogenes. A number of methods exist to assay this enzyme. All measure pyrrolidonyl-peptidase by the ability of the bacterium to cleave L-pyrrolidonyl-beta-naphthylamide to form free beta-naphthylamine and L-pyrrolidone-carboxylic acid. Free beta naphthylamine is then reacted with N,N-dimethylamino-cinnamaldehyde to form a red color complex. These methods are generally expensive and require a 2-4 h incubation period before results are available. A method, which employs the substrate dried on paper discs and can be easily made, is described herein. It is simple to perform, inexpensive, rapid, and has a long storage life. The results of this constitutive method are equivalent to those obtained using a commercial system. PMID- 2905763 TI - Tight linkage between the syndrome of generalized thyroid hormone resistance and the human c-erbA beta gene. AB - Multiple cDNAs belonging to the c-erbA gene family encode proteins that bind T3 with high affinity. However, the biological functions of these multiple thyroid hormone receptors have not yet been clarified. Generalized thyroid hormone resistance (GTHR) refers to a human syndrome characterized by tissue refractoriness to the action of thyroid hormones; several studies have suggested quantitative or qualitative defects in T3 binding to nuclear receptors in certain kindreds. To investigate the biological functions of the c-erbA genes, c-erbA alpha and c-erbA beta, we tested the hypothesis that an abnormal c-erbA gene product is present in GTHR by examining these genes in members of one kindred. Restriction enzyme analysis failed to identify an abnormal pattern in affected individuals suggesting no rearrangements or large deletions. However, we demonstrated that the gene conferring the GTHR phenotype is tightly linked to the c-erbA beta locus on chromosome 3. This linkage strongly suggests that the c-erbA beta gene is important in man as a thyroid hormone receptor and identifies a putative c-erbA beta mutant phenotype with central nervous system, pituitary, liver, metabolic, and growth abnormalities. PMID- 2905762 TI - [Early diagnosis of diabetic nephropathy. Significance and clinical usefulness of albuminuria and enzymuria]. PMID- 2905764 TI - A steroid response element can function in the absence of a distal promoter. AB - The glucocorticoid-progesterone responsive element (GRE/PRE) of the tyrosine aminotransferase (TAT) gene is a steroid-inducible enhancer. We show that the GRE/PRE can also work in the absence of a distal promoter element when located 5' to the ovalbumin TATA box. The GRE/PRE in this position retains progesterone or glucocorticoid receptor and hormone dependency for the induction of gene expression. Initiation of transcription occurs correctly, and induction occurs at the mRNA level. These data indicate that a steroid-inducible enhancer can function without a distal promoter element. PMID- 2905766 TI - [Prevention of hemorrhages in esophageal varices]. PMID- 2905767 TI - [Fertility disorders in man during treatment with sufasalazine]. PMID- 2905765 TI - Interactions of isamoltane (CGP 361A), an anxiolytic phenoxypropanolamine derivative, with 5-HT1 receptor subtypes in the rat brain. AB - Isamoltane (CGP 361A; (1-(2-(1-pyrrolyl)-phenoxy)-3-isopropylamino-2-propanol hydrochloride), a beta-adrenoceptor ligand (IC50 = 8.4 nmol/l) which has reported activity as an anxiolytic in man was found to be a reasonably active inhibitor of the binding of [125I]ICYP to 5-HT1B recognition sites in rat brain membranes with 27-fold selectivity (IC50 = 39 nmol/l) as compared to the inhibition of binding of [3H]8-OH-DPAT to 5-HT1A receptors (IC50 = 1070 nmol/l). This selectivity was considerably greater than that observed for other beta-adrenoceptor ligands including propranolol (5-HT1A/5-HT1B ratio = 2), oxpenolol (3.5) and cyanopindolol (8.7). The 5-HT1B activity of the compound resided in the (-) enantiomer. (-)-Isamoltane had weak activity (IC50 3-10 mumol/l) at 5-HT2 and alpha 1-adrenoceptors. The compound was devoid of activity at a number of other central neurotransmitter recognition sites including the 5-HT1C site. Isamoltane increased the electrically evoked release of [3H]5-HT from prelabeled rat cortical slices in a manner similar to that of cyanopindolol. While both compounds were similar in potency to methiothepin, they had lower efficacy. Oxprenolol was less potent that both isamoltane and cyanopindolol while propranolol was essentially inactive. The effects of the compounds on 5-HT release appeared to be correlated with their 5-HT1B rather than 5-HT1A activity. In vivo, isamoltane increased 5-HTP accumulation in rat cortex following central decarboxylase inhibition at doses of 1 and 3 mg/kg i.p. At higher doses this effect was gradually diminished. Similar, but less clearcut results were obtained with cyanopindolol and oxprenolol, but propranolol was ineffective. No changes in brain tryptophan levels were associated with the isamoltane-evoked changes in brain 5-HTP levels. In reserpinized animals, isamoltane reduced 5-HTP accumulation even at doses which enhanced accumulation of this metabolite when given alone. The effects of the putative 5-HT1B agonist, m trifluoromethylphenylpiperazine (TFMPP), the mixed 5-HT autoreceptor agonist/antagonist/beta-adrenoceptor antagonist, pindolol, the 5-HT uptake inhibitor, CGP 6085A and the MAO-A inhibitor, brofaromine, were not antagonized by pretreatment with isamoltane. The possibility that isamoltane and the other beta-adrenoceptor antagonists are antagonists at 5-HT1B receptors and that their effect on 5-HT synthesis in vivo is the net result of their agonist/antagonist effects at 5-HT1A and 5-HT1B receptors is discussed in relation to the potential mechanism of the anxiolytic activity of isamoltane. PMID- 2905768 TI - [Sir James Black, Nobel laureate 1988]. PMID- 2905769 TI - [The malignant neuroleptic syndrome]. PMID- 2905770 TI - [A differential effect profile of neuroleptic therapy of acute schizophrenic patients? Results of a clinico-naturalistic study]. PMID- 2905771 TI - [Treatment continuity in schizophrenic patients in ambulatory care. A 5-year follow-up]. AB - A hundred schizophrenic patients, who were treated in hospital since 1978, referred for out-patient (OP) treatment and consecutively included in a five-year follow-up investigation, were examined regarding their consistency of OP treatment. 16% were not rehospitalised during these five years, whereas 84% were, half of them within thirteen months of hospital discharge. 92% of all the patients, discontinued or ended their OP treatment after an average of 16.2 months. Five years after the beginning of the investigation, 41% were in touch with the OP clinic. The choice of depot neuroleptics instead of short-working ones had no influence on the occurrence of further hospital admissions but shows a correlation with consistency of treatment. PMID- 2905772 TI - [Withdrawal phenomena in stepwise withdrawal of benzodiazepines]. PMID- 2905773 TI - Multiple pertussis toxin substrates as candidates for regulatory G proteins of adenylate cyclase coupled to the somatostatin receptor in primary rat astrocytes. AB - The involvement of G proteins in receptor mediated astroglial cAMP formation was studied. Isoproterenol or prostaglandin E2 stimulated adenylate cyclase of primary astroglial cells was inhibited by somatostatin. Preincubation of cells with increasing concentrations of islet activating protein (IAP) diminished somatostatin inhibition of adenylate cyclase. At an IAP concentration of 50 ng/ml somatostatin inhibition was completely abolished. Studies on IAP catalyzed 32P ADP-ribosylation of astroglial cell particulate material revealed an incorporation of radiolabel into three polypeptides in the molecular weight range of 41,000-39,000 Dalton. Pretreatment of intact cells with IAP reduced radiolabeling of this molecular species in a concentration dependent manner. No further radiolabeling above background level was detectable after pretreatment of cultures with 10 ng IAP/ml or more. At present, the occurrence of at least three IAP substrates (G proteins) does not permit an identification of the somatostatin receptor coupled G protein. Rather, the finding reveals that astrocytes are endowed with multiple variants of GTP binding proteins likely to be coupled to different receptors. PMID- 2905774 TI - Effects of long-term dietary choline and phosphatidylcholine administration on muscarinic receptors in aged mouse brain. AB - It has been suggested that choline and/or phosphatidylcholine may be beneficial in improving the memory deficits associated with aging and Alzheimer's disease. The effects of long-term choline or phosphatidylcholine treatment on cholinergic receptors in the brain have been investigated. Mice were maintained on one of four diets from 50 days of age until sacrificed at 20-24 months. [3H]-QNB binding in the cortex, hippocampus and striatum was specific, saturable and of high affinity. Animals treated with a phosphatidylcholine-enriched diet displayed a down-regulation of muscarinic receptors in the cortex and hippocampus, reflected by a decrease in Bmax. There were no significant differences in the binding affinities among the treatment groups. Choline levels were unaffected by the various diets, however phosphatidylcholine treatment resulted in an increase in phosphatidylcholine in the cortex and somewhat in the hippocampus. This study indicates that choline and phosphatidylcholine have different effects after long term dietary administration. Phosphatidylcholine treatment results in a down regulation of muscarinic receptors in certain brain areas which appears to be related to an increase in phosphatidylcholine concentration. Any potentially beneficial effects derived from chronic phosphatidylcholine treatment must overcome the apparent down-regulation of muscarinic receptors which may occur. PMID- 2905775 TI - A quantitative morphological assessment of the effect of lidoflazine and deferoxamine therapy on global brain ischaemia. AB - The effect of the combination of two drugs, i.e. lidoflazine (a calcium antagonist), and deferoxamine (an iron chelator) was evaluated following 15 min global brain ischaemia (GBI) and reperfusion in dogs in a randomized blind study. GBI was produced by complete cardiac arrest of 15 min duration. Histopathological analysis performed on in situ fixed brains 40 h post-resuscitation revealed diffuse microhaemorrhages in the control group. These were noted rarely in the treatment group, the mean value of foci of microhaemorrhages/20 low power fields (LPF) being 5.2 in the treatment group versus 28 in the control group (p less than 0.001). Diffuse coagulative necrosis of neurons (ischaemic cell change) in the cerebral cortex, especially lamina 3, hippocampus, striatum, brain stem and cerebellum was present in all cases. Quantitation of the degree of cellular damage obtained by counting the number of anoxic neurons (in consistent regions of the brain) with the use of an image analysis system, revealed no significant difference between the 2 groups. The mean percentages of the ischaemic neurons in the control group in the various areas studied were: parietal cortex, 22.25; hippocampus, 50.37 and cerebellum (Purkinje cells), 66.75; and in the treatment group 25.3, 55.04 and 70.6 respectively. Thus, the lidoflazine-deferoxamine regimen significantly reduced the incidence of microhaemorrhages in the brain, but it did not have any protective effect against anoxic neuronal injury 40 h post-ischaemia in this experimental model of GBI of 15 min duration. PMID- 2905776 TI - Polyamine inhibition preserves somatosensory evoked potential activity after transient cerebral ischaemia. AB - We tested the hypothesis that the increase in polyamines observed after cerebral ischaemia is related to deficits in electrocortical function as measured by somatosensory evoked potential (SEP). Adult Mongolian gerbils were anaesthetized with ketamine and prepared for monitoring SEP, cerebral blood flow (CBF) in parietal and frontal regions by H2 clearance, and for bilateral carotid artery occlusion (BCO). Seven animals served as controls and received saline. Another 7 animals were treated with the ornithine decarboxylase inhibitor, difluoromethylornithine (DFMO) (100 mg/kg I.P.) just prior to 40 min BCO followed by 4 h reperfusion. With BCO, both CBF and SEP declined significantly. In control animals, CBF fell from basal 37.8 +/- 4.7 cc/100 g/min to 2.9 +/- 1.2 cc/100 g/min and recovered to 22.7 +/- 3.5 cc/100 g/h over the 4 h reperfusion period. DFMO treatment did not alter this CBF pattern. SEP amplitude declined to 11.3 +/- 3.2% basal during occlusion. DFMO preserved SEP during ischaemia (35.5 +/- 16.8% basal) and remained significantly more preserved during reperfusion (p less than 0.05). These results suggest that polyamines are involved in the progressive decline in neuroelectrical function which occurs during occlusion/reperfusion in the Mongolian gerbil. The observation that polyamine inhibition preserves electrical function despite not altering blood flow indicates that the effects of polyamines are not manifested at the level of the vasculature but perhaps at the neuronal membrane. PMID- 2905777 TI - Cerebral protective effect of flunarizine in a canine model of cerebral ischaemia. AB - To test the effect of flunarizine on cerebral ischaemia, 15 dogs were subjected to ischaemia, using the 'canine model of the completely ischaemic brain regulated with a perfusion method' in which the cerebral blood flow (CBF) can be fully regulated. Five animals served as untreated controls, 10 received flunarizine, a calcium antagonist (1 mg/kg in 5 dogs and 3 mg/kg in 5 dogs), before the ischaemic period. After 1 h CBF was restored and recovery of the electrical activity of the brain and the degree of brain swelling were observed for 3 h. At the end of the experiments, the degree of extravasation of Evans blue was examined. Remarkable recovery of EEG was found in the groups given flunarizine when compared with untreated controls. However, no significant difference was found between untreated controls and flunarizine treated groups for the degree of brain swelling and the degree of extravasation of Evans blue. These results suggest that the treatment of flunarizine is of benefit for functional recovery against cerebral ischaemia, but does not suppress ischaemic brain oedema. PMID- 2905778 TI - Effect of stimulation in three subcortical sites on the thalamocortical augmenting response in the cat. AB - The thalamocortical augmenting response is a complex multineuronal response which can be elicited by repetitive stimulation of the ventrolateral thalamus. A major function of the ventrolateral thalamus is known to be a result of its participation in central nervous system activity related to motor behaviour. The significance of the thalamocortical augmenting response itself is not known. Since it would be reasonable to relate that response to motor behaviour, we evaluated the effect on the thalamocortical augmenting response of the stimulation of two other central nervous system structures which are also thought to participate in motor control, the cerebellum and the red nucleus. We conclude that at least part of the effect of red nucleus stimulation on the thalamocortical augmenting response is exerted through a rubro-olivo-cerebellar pathway. We then compared the effects of red nucleus and of cerebellar stimulation to the effect of stimulating a non-motor mesencephalic site, the periaqueductal gray. The changes induced in the thalamocortical augmenting response appear not to be fully explicable solely in terms of changes in motor behaviour. PMID- 2905779 TI - Anticonvulsive and convulsive effects of lidocaine: comparison with those of phenytoin, and implications for mechanism of action concepts. AB - The anticonvulsive action of lidocaine was tested in mice against a series of convulsants, and its profile of action compared with that of phenytoin. Both agents antagonized seizures induced by ouabain or glutamate (injected i.c.b.), effects attributable to reduction of the sodium conductance of neuronal membranes. Lidocaine and phenytoin were relatively ineffective against convulsants that act on synaptic chloride channels via the GABA-ionophore receptor complex. At higher dose levels, both lidocaine and phenytoin are excitatory within limited ranges. Lidocaine-induced seizures were potentiated by phenytoin, and antagonized by chlordiazepoxide, phenobarbital, valproate, trimethadione and muscimol, but not by ethosuximide. This profile of action is similar to that of bicuculline, suggesting that lidocaine may bind to the GABA recognition site and to another site in the GABA-ionophore receptor complex. Phenytoin-induced excitation was antagonized by chlordiazepoxide, less effectively by phenobarbital or trimethadione, only minimally by valproate, and not by trimethadione or muscimol. Phenytoin is known to bind to picrotoxin and benzodiazepine receptor sites; these findings suggest that it may be excitatory at one or both of these sites. PMID- 2905780 TI - Relation of supersensitivity to cerebral vasospasm induced by oxyhaemoglobin. AB - There have been reports that superior cervical ganglionectomy (SCG) is effective as a treatment for cerebral vasospasm following subarachnoid haemorrhage (SAH). On the other hand, denervation supersensitivity is supposed to play an important role in vasospasm. The two accounts contradict each other. To investigate this problem, various examinations were performed using the exposed basilar arteries of cats. We have accepted that oxyhaemoglobin (Oxy-Hb) is an important spasmogenic substance. Therefore, the change in vascular reactivity to Oxy-Hb was investigated after various kinds of denervations. It was confirmed that Oxy-Hb has no adrenergic receptor agonist properties because the Oxy-Hb inducing vasospasm was not suppressed by Prazosin or phenoxybenzamine. As a result of this, it is not likely that augmentation of Oxy-Hb inducing vasospasm is caused by deviation supersensitivity. Thus, the non-deviation supersensitivity became a topic of investigation. The basilar arteries were denervated by chemical treatment (reserpine, 6-hydroxydopamine) or bilateral SCG to examine the change in the reactivity to noradrenaline or Oxy-Hb. An increase in reactivity to noradrenaline was observed with the denervations. In contrast, no change in reactivity to Oxy-Hb was found. In conclusion, it was observed that deviation and non-deviation supersensitivity do not participate in vasospasm, in so far as vasospasm is caused by Oxy-Hb. PMID- 2905781 TI - Brain ornithine decarboxylase activity following transient cerebral ischaemia: relationship to cerebral oedema development. AB - Ornithine decarboxylase (ODC) activity, the first and generally rate-limiting enzyme for polyamine synthesis, is stimulated in permanent focal cerebral ischaemia in areas of incomplete ischaemia which are developing ischaemic brain oedema. As polyamines are ubiquitous ornithine-derived molecules which are obligatory in cold-induced vasogenic oedema, we studied the effect of transient dense cerebral ischaemia with reperfusion on ischaemic oedema development and ODC activity. Fifty-nine Mongolian gerbils were anaesthetized with ketamine hydrochloride (160 mg/kg i.p. plus supplementation as needed). Both common carotid arteries were isolated and a tracheotomy placed in position. EEG was monitored with needle electrodes and temperature maintained at 37-38 degrees C. Twenty-nine gerbils underwent 40 min of bilateral carotid artery occlusion followed by reperfusion times of 10 min, 1, 2, 4, 6 or 8 h. Non-ischaemic control groups were monitored for equal intervals. At sacrifice, the brain was rapidly removed and forebrain samples analysed for ODC activity (enzymatic assay) and cerebral oedema (gravimetric determination). Marked loss of EEG amplitude was noted in all gerbils subjected to bilateral carotid artery occlusion. Ischaemia produced significant levels of cortical oedema throughout the reperfusion period (maximal decrease in specific gravity at 4 h postischaemia; control: 1.0456 +/- 0.0013; ischaemia: 1.0355 +/- 0.0021, mean +/- SD; p less than 0.0001). Significant subcortical oedema was produced at 10 min, 2 and 4 h postischaemia. A biphasic response was observed in brain ODC activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2905782 TI - Sequential measurement of somatosensory evoked potentials in a canine model of hemispheric ischaemia. AB - We have previously shown that occlusion of 6 canine intracranial vessels produces profound hemispheric ischaemia and abolishes the ipsilateral SSEP. In the present study, this work was extended to ascertain the differential contributions of 6 intracranial vessels to SSEP function. Five dogs underwent craniotomy, brain retractions, and ipsilateral arterial microdissection, and were prepared for SSEP recordings. Stimulation-recording sequences were performed firstly prior to craniotomy, secondly following craniotomy and microdissection and thirdly following sequential occlusion of each of 6 vessels: (a) anterior cerebral (A2), (b) ethmoidal, (c) ophthalmic, (d) middle cerebral (MCA), (e) posterior communicating (PCoA), and (f) posterior cerebral artery. Individual SSEP amplitudes and latencies were measured and averaged and values for each wave were compared statistically to baseline values and to the immediately preceding value. Two thalamocortical potential components were identified: an early wave (6-10 ms) and a late wave (10-15 ms). No significant amplitude declines between waves occurred with A2, ethmoidal, and ophthalmic occlusions. Following MCA occlusion, amplitude decreased to 49.1% and 34.5% of baseline in the early and late waves respectively; a significant decrease (p less than 0.05) both from baseline and from post-ophthalmic occlusion. Further occlusions (PCoA and posterior cerebral) produced progressive declines in amplitude to a nadir of 12.5% (early) and 2.1% (late) of baseline. Although latency did increase slightly from baseline with each occlusion (5-7% total), no consistent and significant latency changes were identified.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2905783 TI - Patterns of EEG frequency content during experimental transient ischaemia in subhuman primates. AB - EEGs were recorded with depth electrodes in 8 monkeys undergoing transient middle cerebral artery ligation. Electrodes measured EEG, cerebral blood flow (CBF), and tissue oxygen simultaneously during and after occlusion. An EEG frequency analysis was performed. Electrode sites were examined microscopically, and infarction size, tissue vacuolization index, and neuronal morphology were described quantitatively. Serial neurological examinations were performed. Two patterns of EEG frequency change were delineated, dependent upon degree of ischaemia. Mild ischaemia, as indicated by less severe clinical deficits, higher CBF during occlusion, and minor pathological changes was associated with large increases in slow EEG activity and decreases in fast EEG activity during occlusion, with recovery of slow activities to baseline, but continued suppression of fast activities 24 h later. Severe ischaemia was associated with suppression of both fast and slow frequencies during occlusion, with slow activities returning to baseline and fast activities remaining suppressed 24 h later. The best quantitative EEG indicator of severity of ischaemia was suppression of slow wave activity during occlusion. The best EEG indicator that an ischaemic event had occurred 24 h previously was continued suppression of fast EEG activities. These data may be helpful in the design of EEG frequency analysis studies for monitoring the time course of human cerebral ischaemia and for retrospective diagnosis of transient ischaemic attacks (TIAs). PMID- 2905784 TI - Reserpine, para-chlorophenylalanine and fenfluramine antagonise cisplatin-induced emesis in the ferret. AB - The involvement of 5-hydroxytryptamine (5-HT) with cisplatin-induced emesis in the ferret was investigated using reserpine, para-chlorophenylalanine and fenfluramine. Pretreatment with reserpine (5 mg/kg, 24 hr), fenfluramine (5 mg/kg, 4 days) or para-chlorophenylalanine (100 or 400 mg/kg, 4 days) antagonised cisplatin-induced emesis. All treatments reduced the levels of 5-HT in the area postrema and at other cerebral sites, but whilst this action was relatively selective for small doses of para-chlorophenylalanine [only modest effects on noradrenaline (NA) and no change in the content of dopamine (DA) in the area postrema], other treatments reduced levels of dopamine and noradrenaline. Data are discussed in terms of an involvement of 5-HT/catecholamines in the area postrema with the mediation of emesis induced by cisplatin. PMID- 2905785 TI - Synchronization of the EEG and sedation induced by neuroleptics depend upon blockade of both D1 and D2 dopamine receptors. AB - Blockade of dopamine (DA) receptors by neuroleptics tends to produce sedation, as shown by increased sleeping time, reduction of the arousal response to sensory stimuli and slowing of the electrical (EEG) activity of the brain. The EEG and behavioural effects of the selective compounds, SCH 23390 and raclopride, which block either D1 or D2 receptor subtypes, respectively were evaluated. Groups of rabbits were prepared for the measurement of EEG activity (neocortex and hippocampus). The EEG was analyzed visually and by spectral power analysis. Gross behaviour was also observed. The D1 antagonist, SCH 23390, by itself (0.03-0.3 mg/kg i.v.) produced small changes in the EEG and no evidence of sedation. Periods of slow waves occurred sporadically. Computerized EEG analysis showed moderate increases of total power density. The D2 receptor blocker, raclopride, alone (1-3 mg/kg i.v.) produced changes of the activity of the EEG, mostly, short periods of slow waves and slight increases of total power. No sedation was noted. Although both selective antagonists were studied at larger doses than those minimally effective, they produced slight EEG and behavioural changes which were not comparable with the marked actions produced by classical neuroleptics, such as haloperidol. However, when raclopride (1 mg/kg) was given after treatment with SCH 23390 (0.03 mg/kg) there was a marked synchronized activity in the EEG, associated with a state of sedation and diminished responsiveness to sensory stimuli. The data indicate that EEG synchronization and sedation, classically associated with treatment with neuroleptics, do not depend upon the selective blockade of either D1 or D2 receptors but, instead, require concurrent blockade of both subtypes of receptor. PMID- 2905786 TI - Modulation of morphine-induced EEG and behavioral effects by dynorphin A-(1-13) in non-tolerant and morphine-tolerant rats. AB - The purpose of the present study was to assess effects of dynorphin A-(1-13) on morphine-induced changes in electroencephalographic (EEG) spectral power and morphine-induced suppression of slow-wave sleep in non-tolerant and morphine tolerant rats. Adult female Sprague-Dawley rats were implanted with chronic cortical EEG electrodes, electromyographic electrodes in the temporalis muscle and with intracerebroventricular (i.c.v.) cannulae and, in some cases, additional intravenous (i.v.) cannulae. Injections of morphine (i.c.v., 20 micrograms/rat) produced a biphasic EEG and behavioral response, composed of 2-3 hr of slow-wave bursts and increased spectral power (0-4 Hz) in the EEG, associated with behavioral stupor, followed by 2-3 hr of EEG and behavioral arousal. Dynorphin (i.c.v., 20 micrograms/rat), administered 10 min before injections of morphine in non-tolerant rats, antagonized morphine-induced increases in spectral power of the EEG and morphine-induced suppression of slow-wave sleep. In addition, EEG power spectra obtained after intraventricular administration of morphine from rats, treated with dynorphin and morphine intraventricularly 24 hr earlier, were qualitatively similar to those previously found after acute administration of kappa opioid agonists. In morphine-tolerant rats, pretreatment with dynorphin given intraventricularly, 10 min prior to intraventricular administration of morphine, restored morphine-induced increases in EEG spectral power and suppression of slow-wave sleep. The results suggest that dynorphin may modulate the characteristics of opioid receptors. PMID- 2905787 TI - N-methyl-D-aspartate promotes the survival of cerebellar granule cells in culture. AB - Our previous studies on the survival-promoting influence of elevated concentrations of extracellular K+ ([K+]e) on cultured cerebellar granule cells led to the proposal that depolarization in vitro mimics the effect of the earliest afferent inputs received by the granule cells in vivo. This, in turn, might be mediated through the stimulation of excitatory amino acid receptors, in particular the N-methyl-D-aspartate-preferring subtype gating ion channels which are also permeable to Ca2+. Here we report that N-methyl-D-aspartate indeed has a dramatic effect on the survival in culture of cells derived from dissociated cerebella of 7-8-day-old rats and cultured in media containing 'low' [K+]e (5-15 mM). In addition to the visual inspection of the cultures, the effect of N-methyl D-aspartate was quantitatively evaluated, using estimates related to the number of viable cells (determination of DNA and of reduction rate of a tetrazolium salt). Furthermore, proteins which are relatively enriched in either nerve cells (neuronal cell adhesion molecule, D3-protein and synaptin) or in glia (glutamine synthetase) were also measured. The findings showed that the rescue of cells by N methyl-D-aspartate involved primarily nerve cells and that the survival requirement for N-methyl-D-aspartate, as for high K+, developed between 2 and 4 days in vitro. The effect depended on both the concentration of N-methyl-D aspartate and the degree of depolarization of the cells: both the potency and the efficacy of N-methyl-D-aspartate were increased as [K+]e was raised from 5 to 15 mM, at which range K+ on its own has little if any influence on granule cell survival. These characteristics are consistent with the voltage-dependence of ion conductance through the N-methyl-D-aspartate receptor-linked channel. The most pronounced effect of N-methyl-D-aspartate was obtained in the presence of 15 mM K+, when cell survival approached that obtained in 'control' cultures (grown in 25 mM K+-containing media without N-methyl-D-aspartate), and the potency of N methyl-D-aspartate (half-maximal effective concentration, EC50, about 20 microM) was similar to its known affinity in binding to cerebral membranes. The effect of N-methyl-D-aspartate was blocked by the specific receptor antagonist 2-amino-5 phosphonovalerate, which also reduced the limited survival of cells in cultures grown in 'low' K+ in the absence of N-methyl-D-aspartate.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2905788 TI - In vitro and in vivo release of neurokinin A-like immunoreactivity from rat substantia nigra. AB - In vivo and in vitro perfusion techniques have been used to study the release of neurokinin A-like immunoreactivity from the rat substantia nigra. Potassium depolarization and electrical field stimulation evoked calcium-dependent release from nigral slices. Potassium depolarization was also effective in vivo. Tetrodotoxin (1 microM) completely blocked electrically stimulated release but only diminished release in response to depolarizing potassium. Neurokinin A-like immunoreactivity release showed frequency dependence and a clear facilitation phenomenon between 5 and 25 Hz. High-performance liquid chromatography analysis of the immunoreactivity released in vitro revealed the presence of neurokinin A, neuropeptide K and neurokinin B, along with their sulphoxide forms. A marked depletion of neuropeptide K and neurokinin B content was observed when the tachykinin content of the nigral slices was examined before and after stimulation. However, the neurokinin A content of the slices was unchanged or even increased, suggesting an accelerated processing of neurokinin A precursors during the stimulation. The tachykinin peptides were degraded at different rates by substantia nigra homogenates; degradation was fastest for neuropeptide K and slowest for neurokinin A. The addition of a mixture of peptidases inhibitors (thiorphan, phosphoramidon, bestatin and captopril) substantially reduced the degradation of all three tachykinins, but did not completely block degradation. GABA-A receptor antagonists such as bicuculline and, particularly, picrotoxin potentiated the stimulated neurokinin A-like immunoreactivity release in vitro, but the GABA-agonist muscimol had no effect. Picrotoxin was even more potent in vivo. The results presented in this study demonstrate that neurokinin A, neuropeptide K and neurokinin B can be released by depolarizing stimuli from rat substantia nigra. Furthermore, the features exhibited by this release suggest that these peptides may have a neurotransmitter/neuromodulator role in the rat substantia nigra. PMID- 2905790 TI - Ba2+-induced ATP release from adrenal medullary chromaffin cells is mediated by Ba2+ entry through both voltage- and receptor-gated Ca2+ channels. AB - We have measured on-line the exocytotic secretion of ATP from adrenal medullary chromaffin cells induced by Ba2+ using a luciferin/luciferase assay. We have found that Ba2+-induced ATP release requires the entry of Ba2+ through either voltage- or receptor-gated Ca2+ channels. This conclusion is based on the observations that short preincubations with low concentrations of either nicotine or K+ greatly enhance Ba2+-induced ATP release and that this augmentation can be blocked with the nicotinic receptor antagonist, hexamethonium, and the Ca2+ antagonist, nifedipine, respectively. Moreover, both nicotine and K+ stimulate 133Ba2+ uptake, which in the case of K+ is inhibited by nifedipine. These results support the hypothesis that the cellular events leading to Ba2+-induced secretion coincide at least in part with the events leading to Ca2+-dependent exocytosis. PMID- 2905789 TI - DARPP-32, a dopamine- and cyclic AMP-regulated phosphoprotein in tanycytes of the mediobasal hypothalamus: distribution and relation to dopamine and luteinizing hormone-releasing hormone neurons and other glial elements. AB - The distribution of a dopamine- and cyclic adenosine-3':5'-monophosphate (cAMP) regulated phosphoprotein with an apparent molecular weight of 32,000 (DARPP-32) was investigated in the rat diencephalon and monkey hypothalamus by use of immunohistochemical techniques. In addition to single cells located peri- and paraventricularly in hypothalamus and thalamus in the rat, and ependymal cells, DARPP-32-immunoreactivity was found to be present in a subpopulation of ependymal tanycytes. These DARPP-32-positive tanycytes lined the walls and floor of the third ventricle, sending processes towards the arcuate nucleus, surrounding blood vessels in this nucleus, and continuing towards the median eminence, where they abutted on portal vessels. A second group of DARPP-32-positive tanycytes with cell bodies within the median eminence was also observed. Simultaneous labeling with antiserum against tyrosine hydroxylase, a presumptive marker for tuberoinfundibular dopamine neurons, revealed a close relation to DARPP-32 containing tanycytes in several anatomical locations. Thus, in the periventricular area DARPP-32-positive tanycytes ensheathed tyrosine hydroxylase positive processes. These processes, presumably representing dopaminergic dendrites, virtually penetrated between the ependymal cells to the ventricular space and thus perhaps established direct contact with the cerebrospinal fluid. Tyrosine hydroxylase-terminals were also observed in close association with DARPP 32-immunoreactive tanycytes in the rat median eminence. However, in view of the density of DARPP-32-positive processes in the external layer of the median eminence, the DARPP-32 processes may be related to a number of other types of nerve endings, including luteinizing hormone-releasing hormone, as shown in this study. The close association of DARPP-32-immunoreactive processes with tyrosine hydroxylase- and luteinizing hormone-releasing hormone-immunoreactive nerve endings in the rat was directly visualized at the ultrastructural level using triple-labeling immunocytochemistry. Both the ultrastructural analysis and immunohistochemistry at the light microscopic level, comparing the distribution of DARPP-32 and glial fibrillary acidic protein, indicated the presence of two types of glial processes in the median eminence. The electron microscopic studies also suggested the presence of both DARPP-32-positive and DARPP-32-negative glial processes in the external layer of the median eminence.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2905791 TI - Characterization of glutamate receptors induced in Xenopus oocytes after injection of rat brain mRNA. AB - Xenopus oocytes in which poly(A)+ mRNA isolated from rat brains were previously injected, exhibited at least 3 categories of current responses to excitatory amino acids. They were oscillatory responses to glutamate (Glu) or quisqualate (QA), smooth large responses to kainate (KA), and smooth small responses to Glu and QA. Oscillatory responses were mediated by a metabotropic type of Glu receptor which is coupled to a G-protein but not directly to an ionic channel. Amplitudes of smooth Glu responses and smooth QA responses were similar in size, and were not additive to each other, suggesting a common receptor mediating both responses. L-Glutamylglycine inhibited KA responses in a competitive manner without affecting smooth Glu/QA responses, indicating that KA and smooth Glu/QA responses were mediated by separate receptors. From these results, it was concluded that the injection of rat brain mRNA induced at least 3 different glutamatergic receptors: receptors mediating (a) KA responses and (b) smooth Glu/QA responses, and (c) the metabotropic Glu receptor. The former two may most likely correspond to Glu receptor subtypes preferring KA and QA, respectively, as seen in the brain. PMID- 2905792 TI - Simulations of enhanced malaria transmission and host bias induced by modified vector blood location behaviour. AB - Monte Carlo simulations were developed to assess the potential impact of parasite pathology on vector salivary function as well as of host haemostasis on transmission. Assuming that a proportion of desisting vectors switch host following failure to locate blood, we demonstrate three possible consequences: (1) infected vectors contact more hosts than non-infected host, (2) non-infected vectors are biased to infected hosts, independently of attraction, and (3) an exponential relationship exists between parasite load and transmission. We discuss possible epidemiological implications. PMID- 2905793 TI - [Developmental abnormalities and disorders in children with hemophilia]. PMID- 2905794 TI - [Analysis of the poor visualization of the pancreas on ultrasonography]. PMID- 2905795 TI - Information processing, psychological performance and anxiolytic drugs. AB - Clinical anxiety states can be regarded as an exaggerated manifestation of the usual psychological and emotional stresses experienced by an individual adjusting his affectual, cognative and cognitive systems to cope with the vagaries and pressures of everyday life. PMID- 2905796 TI - Experiences of a stress clinic. AB - The Stress Clinic has been established for the systematic investigation and quantification of various stress factors that may produce adverse effects on health. Nine areas are investigated: social habits, social relationships, life events, psychiatric, sexual, sleep, geriatric, menstrual, and stress and the heart. The degree of stress in each area is quantified and a Stress Profile constructed for each patient. The Stress Profile can then be used to determine in which areas stress is most important and appropriate treatment can then be prescribed. In a preliminary analysis, the commonest principal diagnosis was depression (47%), followed by anxiety (27%), whilst in 18% the main stress was insomnia and in three patients an organic illness (7%). The Stress Profile is also used to assess improvement and significant reduction in many of the main stress areas has been demonstrated, coincident with response to treatment. In particular, we have been using centrally acting beta-blocking drugs in the treatment of anxiety and panic attacks with similar results. PMID- 2905797 TI - The treatment of tranquilizer dependence by propranolol. AB - Forty four subjects were treated for benzodiazepine dependence. The withdrawal programme lasted for 10 weeks and included regular group support sessions. Patients were also treated with either propranolol, placebo or "no pill" under double blind conditions. Twenty three patients complied with the full treatment regimen and completed the trial. The outcome of treatment was moderately successful, with 8 out of the 23 patients stopping their tranquilizers and a further 11 achieving a reduction of 50% or more of their original benzodiazepine dose. Tranquilizer dependence is a difficult condition to treat, but preliminary results suggest that propranolol is helpful in reducing the symptoms of benzodiazepine withdrawal. PMID- 2905798 TI - The treatment of anxiety with beta-blocking drugs. AB - Evidence supporting the efficacy of beta blockers in anxiety is reviewed. Propranolol and oxprenolol are the most clearly established in efficacy. A placebo-controlled trial is described, in which propranolol and atenolol were both effective in the symptomatic treatment of generalized anxiety in patients who had been referred by their family doctors for specialist treatment. If initial psychological treatment for chronic anxiety is ineffective, and a drug is considered necessary, then a beta blocker or an antidepressant should be considered as first choice in preference to a benzodiazepine. PMID- 2905799 TI - Progression of ochratoxicosis in broiler chickens. AB - The progression of effects induced by administration of ochratoxin A were characterized in young male broiler chickens (Hubbard x Hubbard). The experimental design consisted of four dietary treatments of ochratoxin A (0, 1.0, 2.0, and 4.0 micrograms ochratoxin A/g feed) and 11 replicates of 10 broilers/replicate. Broilers were housed in electrically heated batteries with feed and water available ad libitum. Broilers were weighed, bled, killed by cervical dislocation, and necropsied at 3, 6, 9, 12, 15, 18, and 21 days of age. Toxicity of ochratoxin A to broilers was evident as early as 6 days of age, when significant (P less than .05) growth depression occurred at 4.0 micrograms dietary ochratoxin A/g feed. Dietary ochratoxin A significantly increased the relative weights of the liver, kidney, spleen, pancreas, and gizzard. Anemia, characterized by a significant decrease in packed-cell volume and hemoglobin levels, was present during ochratoxicosis. Hepatotoxicity of dietary ochratoxin A was evident through an observed significant reduction in serum levels of total protein, albumin, globulin, cholesterol, triglyceride, and blood urea nitrogen, and a significant increase in the serum activities of gamma glutamyl transferase and cholinesterase. A significant increase in serum uric acid and creatinine levels was indicative of nephrotoxicity. These data provide a description of the progression of ochratoxicosis in broilers that should be useful in diagnosis and in improved understanding of ochratoxicosis. PMID- 2905800 TI - Pseudomonas osteomyelitis can occur in the foot after puncture wounds. PMID- 2905801 TI - Benzodiazepine receptor ligands, memory and information processing. Psychometric, psychopharmacological and clinical issues. International workshop. Puerto Rico, December 1986. PMID- 2905802 TI - Clinical relevance of effects of benzodiazepines on learning and memory. AB - The effects of benzodiazepines on learning and memory are examined in the various clinical situations in which these drugs are used. Alterations in performance arising from the conditions for which benzodiazepines are prescribed are also considered. Current evidence indicates that, in anxious patients, as in normal volunteers, benzodiazepines impair the acquisition of new information (episodic memory). Although some tolerance may develop to these impairments, deficits are observed even after patients have been taking their medication chronically. Like amnesic patients, benzodiazepine-treated subjects may be unaware of their impaired ability to learn. The effects of the impairments on behavioral psychotherapies are considered. PMID- 2905803 TI - The effect of anxiolytic drugs on memory in anxious subjects. AB - The benzodiazepines (BZs), represented by diazepam, are the class of drugs used most frequently to treat clinical anxiety disorders. Since it is known that acute BZ intake impairs memory function, the effects of BZs on memory were evaluated in chronic users of BZ medications. In addition, the acute effects of diazepam were compared with those of the non-BZ anxiolytic buspirone on memory function in anxious subjects. Memory function was evaluated by a free verbal recall procedure where subjects recalled a list of 16 noncategorized nouns immediately after the word list was read (immediate recall) and again 20 min later (delayed recall). When the chronic BZ users were tested for free verbal recall during their first visit, 4-14 h after their last dose, they did not differ in immediate or delayed recall from an age- and sex-matched group of unmedicated anxious subjects. At a subsequent visit, the acute effects of BZ medications were studied 60-90 min after the subjects took their usual dose. Although acute BZ administration did not alter immediate recall, delayed recall was significantly impaired in the chronic BZ users. Thus, complete tolerance does not develop to the acute memory impairing effects of BZs after long-term use. Acute administration of the anxiolytic drugs diazepam (5 mg) or buspirone (5 or 10 mg) did not alter immediate recall in another group of unmedicated anxious subjects. Diazepam selectively impaired delayed recall of the word list when compared with placebo. In contrast, neither dose of buspirone altered delayed recall. To the extent that such effects on verbal recall tests are reflected in a patient's daily activities, the failure of buspirone to adversely affect memory function could contribute to its usefulness as an alternative antianxiety therapy. PMID- 2905804 TI - Benzodiazepine-induced amnesia and anaesthetic practice: a review. AB - Anaesthetic practice is the only clinical context in which amnesia is a valued property of benzodiazepine drugs, since decreased recall considerably enhances patient tolerance and acceptance or surgical and diagnostic procedures. Research on the amnesic effects of diazepam, midazolam, lorazepam and flunitrazepam, administered via oral, i.v. or i.m. routes to patients undergoing surgical or diagnostic procedures is reviewed. The degree of anterograde amnesia is a function of the drug, the route of administration and the population of patients being assessed. Retrograde amnesia has not been conclusively demonstrated. Amnesia is more profound for cutaneous-tactile and auditory than for visual stimuli, but actual surgical events, or emotionally laden material, are more likely to be recalled than artificial stimuli. Evidence that the benzodiazepines prevent affective and cognitive processing under general anaesthesia and decrease traumatic postoperative recall of intra-operative events is reviewed. The explanatory value of modern theories of memory for research on benzodiazepine induced amnesia, and the research potential of the surgical setting are outlined. The development of non-sedative anxiolytics and specific benzodiazepine antagonists provides the tools for assessing the contribution of sedative and anxiolytic properties of drugs to their amnesic effects. PMID- 2905805 TI - Lormetazepam, memory and information processing: a review. AB - A review was made of the literature exploring the psychopharmacology of lormetazepam. Results from studies show that there can be a general hangover the morning following nocturnal doses of 2 mg. Findings from more recent work have shown that the 1.5 mg dose can disrupt retrieval of information from short-term memory. Lormetazepam 1 mg has no residual sedative effects. A daytime psychopharmacodynamic study showed lormetazepam 1-2 mg to have no disruptive effects 5 h after drug intake. PMID- 2905806 TI - Anterograde and retrograde amnesia after lormetazepam and flunitrazepam. AB - In a pharmacopsychological study, memory impairments after single oral doses of benzodiazepines or placebo were investigated in 40 healthy men aged 20-40 years. The study was designed as a double-blind and placebo-controlled trial. Four independent groups of 10 subjects randomly received either 1 mg lormetazepam, 2 mg lormetazepam, 2 mg flunitrazepam, or placebo. The tests consisted of word lists, picture tests, and syllable pairs (consonant-vowel-consonant trigrams). Tests were performed before drug ingestion, and 1, 2, 3, and 5 h after application. Different test versions were used on each occasion. The target variables were immediate recall (after presentation and a 10-s distraction task) and delayed recall and recognition (after 30 min). Recognition was also tested after 24 h for all five versions. A distinction must be made between anterograde amnesic effects and retrograde amnesic effects. The greatest anterograde memory impairments were observed after 2 mg flunitrazepam (p less than 0.05). Lormetazepam 2 mg produced less marked impairments than flunitrazepam. Results after 1 mg lormetazepam did not differ from those after placebo. Performance in the memory tests was better under benzodiazepines than under placebo as regards material learned before drug ingestion, i.e. the benzodiazepines had not negative retrograde amnestic effects, but rather "promnesic" effects. The results suggest that the extent of the benzodiazepines' amnesic effects--both negative (anterograde) and positive (retrograde)--depends on the dosage and type of substance. PMID- 2905807 TI - Animal model studies of benzodiazepine-induced amnesia. AB - The development of a mouse passive avoidance test as a model for amnesia produced by benzodiazepines is described. The model appropriately classifies the amnesic potential of a wide range of psychoactive drugs as validated by clinical findings. Control experiments indicate that the effect is best described as anterograde amnesia resulting from a failure of consolidation. gamma-Aminobutyric acid (GABA) antagonists had almost no effect on benzodiazepine-induced amnesia, whereas the benzodiazepine-receptor antagonist Ro 15-1788 completely and specifically reversed it. This clinically confirmed finding suggests that benzodiazepine-induced amnesia is mediated through the benzodiazepine-receptor. However, in vivo inhibition of benzodiazepine binding does not correlate well with amnesia in the mouse, and some benzodiazepine-receptor agonists with potent CNS effects in other in vitro models do not produce amnesia. Additional work is needed to clarify what aspects of benzodiazepine receptor occupancy mediate amnesia. PMID- 2905808 TI - Benzodiazepine receptor ligands: tools for memory research in clinical pharmacology. AB - In order to study the time course of amnesic effects of the benzodiazepine hypnotic lormetazepam, and their reversal by the benzodiazepine antagonist Ro 15 1788, a combined visual and auditory memory test was developed, which was designed to allow repeated assessments. Immediate recall as well as delayed free recall and recognition (1 h after drug) were investigated before and after intravenous lormetazepam (0.02 mg/kg) followed 15 min later by intravenous Ro 15 1788 (0.03 mg/kg) or placebo. A third group received placebo followed by Ro 15 1788. Results are based on ten subjects per treatment group and are compared with an age-matched control population (n = 20) without treatment. Immediate and delayed recall as well as recognition in both visual and auditory tests were impaired abruptly after intravenous lormetazepam. These effects were reversed instantaneously after Ro 15-1788, which had no marked effect on these parameters when given alone. Ratings by visual analog scales (1 h after drug administration) indicated concomitant sedation and impaired concentration after lormetazepam, which was attenuated by Ro 15-1788. By itself, Ro 15-1788 had no effect on these measures. Interestingly, the performance in delayed free recall of the visual memory test was significantly enhanced in the lormetazepam group prior to administration. Our results suggest that impaired acquisition of new information after lormetazepam is benzodiazepine receptor mediated and may be associated with a drug-induced enhancement of retrieval of information acquired before lormetazepam administration. PMID- 2905809 TI - Information processing, critical flicker fusion threshold and benzodiazepines: results and speculations. AB - There is evidence to suggest that the rate of information processing, as measured by the critical flicker fusion threshold (CFFT), is slower following some benzodiazepines than others. Changes in CFFT brought about by benzodiazepine administration are usually, but not always, correlated with changes in other measures of cognitive performance and memory. However, the drug-induced changes in information processing and memory cannot be fully explained by simple postulates regarding alterations in the overall level of CNS arousal. Results from a series of studies of the effect of benzodiazepines on measures of CFFT and memory will be reviewed and the utility of CFFT in evaluating the amnesic or mnemonic potential of CNS-active drugs will be assessed. PMID- 2905810 TI - Individual differences in benzodiazepine-induced changes of memory. AB - Antero- and retrograde amnesia are observed as side effects of most types of benzodiazepines. They have rarely been investigated with respect to physical and personality factors, or to prior experiences, present expectations, and emotional states of the subjects, all of which are well known to modify drug response. By reviewing research on benzodiazepine-induced changes of memory in preoperative, anxious, and depressed patients as well as in healthy subjects, it is demonstrated that differences in benzodiazepine-induced amnesic effects may depend on: 1. subject variables like predrug level of anxiety, depressive symptomatology, memory capacity, experiences with benzodiazepine-type drugs, and expectations of treatment outcome, and secondary factors like social environment and treatment setting 2. interactions between these subject variables and type of schedule (times of acquisition, treatment, and testing), type of learning material, and dose of drug. 3. the extent of benzodiazepine-induced changes in anxiety or depression, cortical and emotional arousal (alertness and activity) as well as physiological effects of benzodiazepines Special emphasis should be placed on the investigation of drug-induced changes of covariation between psychological measures which may provide valuable information for differential prediction and on mechanisms of drug action. PMID- 2905811 TI - Study of gamma-glutamyltranspeptidase of abrasive balloon collections from esophagus in an area with high incidence of esophageal cancer. PMID- 2905812 TI - Organization of homeodomain proteins. PMID- 2905813 TI - Neurochemical studies on the mechanism of action of pyritinol. AB - In investigations carried out in young and old rats with pyritinol (pyrithioxin, Encephabol), a substance that is frequently applied in cognitive function disturbances, besides effects on general cerebral functions, possible interactions with cholinergic transmission were determined. The following results were obtained: 1. The adenosine triphosphate (ATP) content of the blood was determined as a possible biochemical parameter of erythrocyte flexibility. After acute oral administration of 30, 100 and 300 mg/kg pyritinol, the ATP content of whole blood increased by 8%, 17% and 20% respectively compared with placebo. 2. According to the literature, brain glucose utilisation is considerably reduced at higher age. This was confirmed in old rats in the investigation presented here. Pyritinol (200 mg/kg p.o.) induced a significant increase in glucose utilisation in striatum, cortex, hypothalamus and cerebellum in 24- to 36-month-old rats. 3. The high-affinity choline uptake in striatal synaptosomes of old rats was significantly lower than that of young ones. Pyritinol (600 mg/kg p.o.) increased choline uptake in young rats as well as in old ones. 4. cGMP can serve as a postsynaptic marker for the activity of the cholinergic system. Pyritinol (200, 600, 1000 mg/kg p.o., 16-23 days) increased the cGMP level in the cortex by 25%, 42% and 71% respectively. Our results are in accordance with the recently described (Martin, 1987) elevation of cortical acetylcholine levels and facilitation of acetylcholine release under pyritinol and extend the functional relevance of these findings to the postsynaptic, cholinergically innervated cortical neurons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2905814 TI - [Possible diagnostic significance of deviations in transmitter metabolism in acute neurologic diseases]. PMID- 2905816 TI - Antipsychotic use in the medically ill. AB - Antipsychotics are of use in a variety of medical settings. They can be used to treat organic mental disorders resulting from the medical illness and its therapy, as well as to control the symptoms of coexisting psychiatric conditions. Antipsychotics also have a variety of nonpsychiatric applications. This paper will review these uses of antipsychotic agents and how their administration must be modified in the medically ill. PMID- 2905817 TI - Use of anti-anxiety drugs in the medically ill. AB - The Stress Clinic at the Maudsley Hospital investigates anxiety due to stress and its pharmacological treatment. Nine stress areas are investigated and their relative severities estimated: social habits, social relationships, life events, psychiatric morbidity, sexual stresses, sleep, stress in old age, menstrual stresses and stress and the heart. From the results a Stress Profile can be constructed for each patient to compare the importance of these different stresses and this can also be used as a measure of change in response to treatment. The benzodiazepine (BZD) anxiolytics can be divided into two groups according to duration of action, medium (8-12 h) and long (30-100 h). Short acting BZD drugs are particularly useful for situational anxiety, when treatment can be interrupted over night and at weekends. To overcome problems of dependence, withdrawal effects, and daytime side-effects, new non-BZD anxiolytics have been developed: buspirone, alpidem and suriclone. These may be particularly useful for long-term treatment of anxiety. Another alternative is the use of adrenergic beta-blocking drugs of which propranolol and betaxolol have been used in the Clinic, because of their relatively high concentration in the brain when taken orally. Anxiety accompanying coronary heart disease and hypertension can be controlled with anxiolytic drugs and other illnesses with an anxiety component are: sexual disorders, menstrual disorders, asthma, gastro-intestinal conditions, dermatological conditions and chronic illnesses such as malignancy and AIDS. Lack of sleep is a subtle form of stress exerting an adverse effect in almost every illness known to man. BZD hypnotics can be divided into four groups: ultra-short acting (3-4 h), short-acting (5-6 h), medium-acting (7-8 h) and long-acting (9-12 h). Depending on the nature of the insomnia, ultra-short-acting and short-acting BZD are particularly convenient with minimal disadvantages. Nevertheless, new non BZD hypnotics are also being developed, i.e. zolpidem and zopiclone. These drugs are relatively short-acting and of equivalent potency to the BZD without problems of dependence etc. Anxiety, as either cause or effect, accompanies many medical illnesses and the use of anti-anxiety drugs as concomitant therapy can both reduce morbidity and improve prognosis. PMID- 2905815 TI - Cellular immunity and the hypothalamic-pituitary axis in major affective disorder: a preliminary study. AB - To assess cellular immune status and the hypothalamic-pituitary axis in patients with major depression, we examined peripheral blood mononuclear cells and measured the plasma levels of four neurohormones. Eleven patients with major depression had increased % of T4 lymphocytes and decreased concanavalin (Con A) stimulated T lymphocyte proliferation when compared with 11 age-, sex-, and race matched control subjects. Percent of total lymphocytes labeled as all T lymphocytes, all B lymphocytes, and natural killer cells did not differ in the two groups, nor did mitogen-induced interleukin-2 production. These findings support theories of interaction between depression and immune cell function. PMID- 2905818 TI - Neurotransmitters in vestibular pathways. PMID- 2905819 TI - In vivo and in vitro release of central neurotransmitters in relation to pain and analgesia. PMID- 2905820 TI - Peptidergic neurons in the nucleus raphe magnus and the nucleus gigantocellularis: their distributions, interrelationships, and projections to the spinal cord. PMID- 2905821 TI - Behavioral correlates of presynaptic events in the cholinergic neurotransmitter system. PMID- 2905822 TI - [Treatment of childhood asthma]. AB - The treatment of childhood asthma should be considered with respect to age, severity and aetiology. Treatment should be instituted early from the first crisis in order to avoid progression to a more severe form. It consists of two aspects: the treatment of the acute episode and the chronic treatment. The treatment of the acute episode consists of using bronchodilators (BD) (rapid release Theophylline and/or beta agonists) to which one might add corticosteroids if the crisis lasts for more than a few hours or seems severe at the outset, an antibiotic should also be used as infection is often a trigger factor in infants. Maintenance treatment is necessary in asthmatics with frequent exacerbations. It should be tailored to the symptomatology and aetiology. The symptomatic treatment consists of a bronchodilator (slow release Theophylline or an atropine-like pharmacological derivative) to which one may add, in severe cases, corticosteroids which may be in the form of aerosol, or as rarely as possible by mouth. The second aspect of treatment relating to the aetiology is the most difficult to apply as childhood asthma is often multi-factorial: in allergic asthma the avoidance of allergens, disodium cromoglycate, ketotifen, and if necessary specific desensitization. In non-allergic asthma, physiotherapy, treatment of infectious foci, particularly ENT (ORL), and attention to psychosomatic features. When asthma is diagnosed and treated early the prognosis is transformed and progress towards chronicity is avoided. PMID- 2905823 TI - [Joint pain, facial skin eruption]. PMID- 2905824 TI - Hypnotic residual effects of benzodiazepines with repeated administration. AB - Performance measures were compared to the multiple sleep latency test (MSLT) as indices to assess tolerance to the residual effects of benzodiazepine hypnotics during repeated nightly administration. Twelve healthy, normal sleepers received flurazepam 30 mg, temazepam 30 mg, and placebo for nine nights in a repeated measures, Latin-square design with 19 nights of recovery separating the treatments. As compared to placebo, both drugs altered sleep stage parameters in the early (nights 1-2) and late (nights 8-9) phases of the study. Hypnotic effects were found for both drugs in the early phase, but diminished for both in the late phase. The subjects' performance the next day was disrupted following treatment with flurazepam, but not with temazepam, during the early phase. Mean sleep latency on the MSLT was reduced by both drugs during the early phase. During the late phase, flurazepam did not disrupt performance but still affected the MSLT. Temazepam affected neither index the next day during the late phase. PMID- 2905825 TI - [Neuroleptics: long-term observations]. PMID- 2905826 TI - [Enzymuria following administration of contrast media in hypertensive rats]. AB - Renal complications may occur in risk patients with pre-existing kidney damage if x-ray contrast media are administered. Nothing is known of the exact mechanisms of these reactions. We examined in rats with long-term renovascular hypertension and resulting nephrosclerosis the low osmolar contrast media ioxaglate, iohexol and iopamidol in respect of their renal tolerance compared with an osmotically equivalent mannite solution. Under the conditions of intravenous pyelography, we observed directly after the administration of all substances (3.5 mg/kg body weight) an enhanced enzymuria of gamma-glutamyl transpeptidase and N-acetyl-beta D-glucosaminidase. The loss of enzyme is mainly due to the osmotic effect of the preparations. The nonionic contrast media iohexol and iopamidol produce a slighter enzymuria than the ionic ioxaglate. PMID- 2905827 TI - Biting activity of Aedes scapularis (Rondani) and Haemagogus mosquitoes in southern Brazil (Diptera: Culicidae). PMID- 2905828 TI - Assessment of effects of amino acids and branched chain keto acids on leucine oxidation in human lymphocytes. AB - Effects of amino acids and branched chain keto acids on leucine transamination and oxidation were assessed in peripheral human lymphocytes. Isoleucine (80-200 mumol/l) and valine (250-500 mumol/l) diminished transamination and oxidation of leucine up to 25%, glutamine (50-1000 mumol/l) up to 55%. alpha-Ketoisocaproic acid (KIC; 200 mumol/l) augmented the activity state of branched chain keto acid dehydrogenase by 40%. It is concluded that in peripheral human lymphocytes (1) isoleucine, valine and glutamine are physiological inhibitors of leucine catabolism, and (2) leucine can promote its own degradation via KIC. PMID- 2905829 TI - The Genain quadruplets. AB - The Genain quadruplets are a unique set of monozygous women who are concordant for schizophrenia but discordant for the severity of their disorder. They were studied by David Rosenthal and colleagues at the National Institute of Mental Health in the late 1950's when they were in their twenties and again in 1981 when they were 51. They are faring about as well now as they ever have in their adult lives. The results of psychological tests, some of which were repeated more than 20 years apart, are discussed, as are the effects of medication on attention and memory. The differential response of the Genains to neuroleptic drugs, as well as certain other findings in the 1981 study, leads to a different conclusion about the discordant severity of their disorder from that reached in 1963 by Rosenthal and Quinn. These observations emphasize the value of long-term followup studies in genetically related individuals, with repeated assessments of the same functions. PMID- 2905830 TI - [Prognostic significance of the T4 lymphocyte count in patients infected with CDC Class II and III HIV]. AB - From 1985 to 1987 101 patients infected with the human immunodeficiency virus (HIV) were seen at our outpatient clinic and prospectively analyzed in a cohort study. We evaluated the follow-up in 41 patients of CDC classes II and III with regard to the number of T-helper lymphocytes (T4) and clinical progression. The patients consisted of 24 i.v. drug addicts, 11 homosexuals and 6 persons with other or multiple risk factors for HIV infection. Patients with a T4 count of less than 400/mm3 at the first visit did not differ significantly with regard to development of AIDS from those with a count of greater than 400/mm3 after a mean follow-up of approximately 1 year. The course of the infection for the individual patient was extremely varied and not predictable by the T4 value. We conclude that the number of the T4-lymphocytes is of no help in assessment of prognosis in the individual patient of CDC classes II and III. PMID- 2905831 TI - [Side-effects of frequently administered hypnotics and sedatives as well as of anxiolytics. Results from a Comprehensive Hospital Drug Monitoring (CHDM) program]. AB - The occurrence and age distribution of patients with adverse drug reactions (ADR) were studied on the basis of a total of 17,653 admissions to the medical divisions of the Zieglerspital Bern and the Anna-Seiler-Haus, Inselspital Bern, during the period 1976-1982. Among this population 12,424 patients (70.4%) happened to have been treated with hypnotics, sedatives or anxiolytics. Results are as follows: 1. The occurrence rate of psychic and neurologic symptoms (with the exception of somnolence and hangover) is 0.14% of all treatments if the casualty category "definitely or probably drug-induced" is considered. For "other ADR" (non-psychic, non-neurologic) the rate is 0.16%. For the benzodiazepine preparations, the psychic and neurologic ADR occurred at about the same rate as for the neuroleptic drugs studied, whereas "other ADR" related to benzodiazepines were observed in only 0.04% of treatments. 2. There is a marked difference in ADR symptoms between benzodiazepines and neuroleptics. With benzodiazepines the most severe reactions were two episodes of shortlived respiratory arrest immediately after intravenous administration. With neuroleptic drugs the most severe symptoms were choreoathetosis, dyskinesia, hyperkinesia and Parkinson's syndrome. There was no fatal reaction. 3. With benzodiazepines there is a slight but significant increase in the occurrence of psychic and neurologic symptoms in the older group of patients, as compared to the younger patients, whereas with neuroleptics there is no age dependence. PMID- 2905832 TI - Report from Stockholm. PMID- 2905833 TI - [Covering skin defects of the sole of the foot using free sensory flap transfer]. PMID- 2905834 TI - Development of a metabolic activation system for the frog embryo teratogenesis assay: Xenopus (FETAX). AB - FETAX (frog embryo teratogenesis assay: Xenopus) is a 96-hr teratogenesis screening assay using embryos of the South African clawed frog, Xenopus laevis. Since Xenopus embryos have limited xenobiotic metabolism through 96 hr of development, we have developed an in vitro metabolic activation system employing Aroclor 1254-induced rat liver microsomes. By adding an exogenous source of mixed functional oxidase (MFO) activity, we may more accurately assess the teratogenic risk of proteratogenic compounds. Xenopus embryos were cocultured with varying concentrations of cyclophosphamide (CP), Aroclor 1254-induced microsomal protein, an NADPH-generating system, and antibiotics in a static renewal fashion for 96 hr. Residual Aroclor 1254 remaining in the microsomes was successfully reduced during purification to levels that had no significant effect on embryo survival and development. The results of three definitive dose-response tests performed with CP revealed that activation reduced the 96 hr LC50 from 8.0 to 1.4 mg/ml (5.7-fold). The 96-hr EC50 (malformation) was reduced from 6.2 to 0.4 mg/ml (15.5 fold). Activation also increased the types and severity of malformation and reduced embryonic growth. Aroclor 1254-induced rat liver microsomes may be used as an acceptable in vitro metabolic activation system for FETAX. PMID- 2905835 TI - Human embryonic cell growth assay for teratogens with or without metabolic activation system using microplate. AB - In vitro microassay for the screening of teratogens was investigated on cancer chemotherapeutic agents sterigmatocystins and benzimidazoles using human embryonic palatal mesenchymal (HEPM) cells. Five thousand cells were inoculated into each well of 96-well microtiter plates, and cultivated for 24 hr, after which the media were changed with new ones that contained various amounts of chemicals; after cultivation for an additional 72 hr, the media were discarded, and cells attached to the tissue plate were fixed and stained with Giemsa's solution; the cell number then was counted by colony counter with three readings for each well. For the metabolic activation, the liver S9 obtained from rats pretreated with phenobarbital and 5,6-benzoflavone and cofactors (S9 mix) were added directly to the HEPM cell cultures along with chemicals. After 6 hr, the cultures were exchanged with a fresh medium and incubated for a further 72 hr. The final IC50 (the concentration that inhibits growth 50%) concentration-finding run had 7 to 11 concentration points (mean, three to four wells). Concentrations of the cancer chemotherapeutic agents that inhibited growth by 50% ranged from 0.001 to 10 micrograms/ml. Sterigmatocystins indicated strong inhibition; among three derivatives, O-acetyl sterigmatocystin was the most potent inhibitor. Benzimidazoles also exhibited an inhibitory action on HEPM cell growth; nitro and chloro groups at the 5 position in 2-(2-pyridyl)benzimidazole were found to be potent substituents. As for the activation of cyclophosphamide in the HEPM cell culture, IC50 was decreased to 1.0 ug/ml by the incubation with S9 mix for 6 hr under our experimental conditions, and sterigmatocystin was found to be activated by S9 mix.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2905836 TI - Evaluation of sister chromatid exchange as an indicator of sensitivity to N-ethyl N-nitrosourea-induced carcinogenesis in rats. AB - Sister chromatid exchange (SCE) frequencies in peripheral lymphocytes are a frequently used endpoint to indicate exposures to genotoxins in groups of humans. The aim of this study was to ascertain, in an experimental design, whether or not SCE rates have any association with the risk of cancer at the individual level in rats exposed to a known carcinogen. Individual SCE rates were determined in three consecutive analyses in cultured blood lymphocytes of 50 adult male Wistar rats. Analyses were done before as well as 24 hr and 7 days after a single intraperitoneal administration of 0, 25, 50, or 75 mg/kg of N-ethyl-N-nitrosourea (ENU). The animals were followed until death; also, the relationship between SCEs and carcinogenic outcome, i.e., the presence or absence of tumors, and their latency period were examined. ENU significantly decreased the life expectancy of the rats. The tumor types most clearly associated with ENU treatment were various gliomas and thyroid-gland and testicular tumors. ENU induced a moderate (maximally 1.6-fold) increase in the mean frequency of SCEs/cell at both sampling times after treatment. The effect was somewhat more pronounced 1 day rather than 1 week after treatment. The mean SCE rates in rats with ENU-specific cancers or in animals with early or multiple tumors did not differ from those in animals that survived no less than 65 weeks or longer without developing tumors. In ENU treated animals with tumors, no relationship was found between the mean SCE rate and survival time. It is concluded that in outbred Wistar rats the SCE response in cultured lymphocytes does not indicate individual susceptibility to the carcinogenic action of ENU. On a group basis, however, animals with high SCE rates were shown to have increased risk of cancer. PMID- 2905837 TI - Studies of mutagenesis and neoplastic transformation by bivalent metal ions and ionizing radiation. AB - We examined the influence of nontoxic concentrations of each of two essential (Zn++ and Mn++) and one nonessential (Ni++) bivalent metal ions on spontaneous and radiation-induced neoplastic transformation and specific gene mutations in mammalian cells. All three metals induced low levels of transformation in mouse BALB/3T3 cells but exerted no mutagenic effect in CHO cells (hprt locus) over a broad range of concentrations. Continuous incubation for 8 or 15 days with each of the metal ions did not enhance the frequency of cell killing, transformation, or mutations induced by acute exposure to x-rays. Zn++, however, had a small but consistent protective effect on the induction of all three endpoints by x irradiation. PMID- 2905838 TI - Mutagenicity of topoisomerase-active agents in bacteriophage T4. AB - Recently, the antitumor agent 4'-(9-acridinylamino)-methanesulfon-m-anisidide (m AMSA) was shown to revert a frameshift mutant of T4 (rFC11), and its mutagenicity was shown to be mediated by T4 DNA topoisomerase II [Ripley et al.: J Mol Biol 200: 665-680, 1988]. Here we report dose-response data on the mutagenicity and toxicity of m-AMSA in T4 rFC11. We find that m-AMSA is among the most potent frameshift mutagens observed in T4, inducing a 10-fold increase in mutant frequency in the absence of toxicity and a 500-fold increase in mutant frequency at 31% survival. In addition to m-AMSA, the topoisomerase-active agents ellipticine, oxolinic acid, and nalidixic acid also reverted rFC11; however, they required concentrations 10-100 times greater than those required by m-AMSA in order to be mutagenic, and they did not produce mutant frequencies as high as those produced by m-AMSA. Unlike m-AMSA, all three agents were mutagenic only at toxic doses. The other agents evaluated--actinomycin D, adriamycin, 9 aminoellipticine, 9-methoxyellipticine, teniposide (VM-26), and novobiocin--were toxic but not mutagenic to T4 rFC11. Thus, m-AMSA appears to be distinctly different from the other topoisomerase-active agents in exhibiting such potent mutagenic activity in T4 rFC11. Because E. coli DNA gyrase may substitute for T4 topoisomerase II, we examined the ability of two inhibitors of E. coli DNA gyrase, novobiocin and nalidixic acid, to inhibit m-AMSA's mutagenicity. Both agents substantially reduced the mutagenicity of m-AMSA in T4 rFC11, further suggesting that topoisomerase mediates the mutagenicity of m-AMSA. PMID- 2905839 TI - Micronucleus induction in mouse and rat fetuses treated transplacentally during histogenesis with mitomycin C and 7,12-dimethylbenz(a)anthracene. AB - During histogenesis, mouse and rat fetuses were treated transplacentally with mitomycin C (MMC) and 7,12-dimethylbenz(a)anthracene (DMBA). The micronucleus (MN)-inducing effects of MMC were analysed in mouse fetal blood and liver; the effects of DMBA were analysed in mouse fetal and rat fetal blood and in maternal bone marrow of both species. Both test substances were clearly clastogenic during the period of development in which the embryos were analysed--i.e., MMC from gestational day 14 until day 18 in mice and DMBA on days 14 and 17 in mice and days 16 and 19 in rats. In mouse fetal liver and blood the MMC-induced MN frequencies did not vary significantly during the whole period. MMC was more effective in fetal blood than in fetal liver. DMBA-induced MN frequencies in maternal bone marrow were slightly higher in rats than in mice. Compared to maternal bone marrow, fetal MN frequencies were about four to five times higher in rats but less than two times higher in mice. Thus, rat fetuses were far more susceptible to the clastogenic action of DMBA than mouse fetuses. These results are discussed with respect to fetal development and maternal/fetal metabolism. PMID- 2905840 TI - [Arm pain due to vascular causes]. PMID- 2905841 TI - Carrier detection in severe (type III) von Willebrand disease using two intragenic restriction fragment length polymorphisms. AB - DNA from a family with a female member affected with severe (type III) vWD was analysed using three restriction enzymes and a partial vWF cDNA probe. Two restriction fragment length polymorphisms (RFLPs) detected with the enzymes Bgl II and Xba I proved to be informative in this family. A 36.0 Kb allele demonstrated with the enzyme Xba I was rare in the general population but very important in this family for segregation analysis of the alleles and their association with the putative defective chromosome. The propositus was homozygous for the 36.0 Kb Xba I polymorphic band and heterozygous for the Bgl II polymorphism. She was the only member of the family showing this allelic pattern. The linkage of the alleles could be determined because her mother was homozygous for the 9.0 Kb Bgl II polymorphism but heterozygous for the Xba I polymorphism. The segregation of the alleles could be traced to the proband's son and a niece. The genotypic analysis revealed that her niece could be considered as carrying a defective gene for severe vWD. PMID- 2905842 TI - Further studies on the mechanisms for the antithrombotic effects of sulfated polysaccharides in rabbits. AB - A recent study (Fernandez et al., Thromb. Haemostas. 1987; 57: 286-93) demonstrated that when rabbits were injected with the minimum weight of a variety of glycosaminoglycans required to inhibit tissue factor-induced thrombus formation by approximately 80%, exogenous thrombin was inactivated approximately twice as fast in the post-treatment plasmas as the pre-treatment plasmas. In this study, we investigated the relationship between inhibition of thrombus formation and the extent of thrombin inhibition ex vivo. We also investigated the relationship between inhibition of thrombus formation and inhibition of prothrombin activation ex vivo. Four sulfated polysaccharides (SPS) which influence coagulation in a variety of ways were used in this study. Unfractionated heparin and the fraction of heparin with high affinity to antithrombin III potentiate the antiproteinase activity of antithrombin III. Pentosan polysulfate potentiates the activity of heparin cofactor II. At less than 10 micrograms/ml of plasma, all three SPS also inhibit intrinsic prothrombin activation. The fourth agent, dermatan sulfate, potentiates the activity of heparin cofactor II but fails to inhibit intrinsic prothrombin activation even at concentrations which exceed 60 micrograms/ml of plasma. Inhibition of thrombus formation by each sulfated polysaccharides was linearly related to the extent of thrombin inhibition achieved ex vivo. These observations confirm the utility of catalysis of thrombin inhibition as an index for assessing antithrombotic potential of glycosaminoglycans and other sulfated polysaccharides in rabbits. With the exception of pentosan polysulfate, there was no clear relationship between inhibition of thrombus formation and inhibition of prothrombin activation ex vivo. PMID- 2905843 TI - Characterization of class II alpha genes and DLA-D region allelic associations in the dog. AB - Human major histocompatibility complex (HLA) cDNA probes were used to analyze the restriction fragment length polymorphism (RFLP) of the alpha genes of the DLA-D region in dogs. Genomic DNA from peripheral blood leucocytes of 23 unrelated DLA D homozygous dogs representing nine DLA-D types (defined by mixed leucocyte reaction) was digested with restriction enzymes (BamHI, EcoRI, Hind III, Pvu II, Taq I, Rsa I, Msp I, Pst I and Bgl II), separated by agarose gel electrophoresis and transferred onto Biotrace membrane. The Southern blots were successively hybridized with radiolabelled HLA cDNA probes corresponding to DQ, DP, DZ and DR alpha genes. Clear evidence was obtained for the canine homologues of DQ and DR alpha genes with simple bi- or tri-allelic polymorphism respectively. Evidence for a single, nonpolymorphic DP alpha gene was also obtained. However, the presence of a DZ alpha gene could not be clearly demonstrated in canine genomic DNA. This report extends our previous RFLP analysis documenting polymorphism of DLA class II beta genes in the same panel of homozygous typing cell dogs, and provides the basis for DLA-D genotyping at a population level. This study also characterizes the RFLP-defined preferential allelic associations across the DLA-D region in nine different homozygous typing cell specificities. PMID- 2905844 TI - [Medico-social aspects of mass screening of children with cryptorchism]. PMID- 2905845 TI - An immunogold labelling method for the enumeration of canine T-lymphocytes. AB - An immunogold procedure using the monoclonal antibody F3-20-7 to canine Thy-l has been used to label T-lymphocytes in peripheral blood samples taken from healthy Beagles. By this method, approximately 64% of peripheral blood lymphocytes were identified as T-lymphocytes. PMID- 2905846 TI - [Effect of therapy with beta-adrenoblockers and vitamin complexes on indices of oxyproline excretion in various hereditary connective tissue diseases]. AB - Excretion of hydroxyproline with urine was studied in 16 children (5-14 years old) with Marphan-Like syndrome and Marphan, Ehlers-Dunlos and Larson syndromes after therapy involving propranolol and a complex of vitamins (ascorbic acid, riboflavin and pyridoxine) and recommended on the basis of echocardiographic analyses. The therapeutic course appears to cause quantitative and qualitative correction of collagen and apparently of elastin fibrilles development. Depending on initial patterns of hydroxyproline excretion and the syndrome form the correction could be complete or partial, while positive effect of the treatment was stable or provisional. The data obtained suggest that the complex treatment developed might be applied as a preoperative therapy of the patients with Marphan like syndrome as well as with syndromes of Marphan and Ehlers-Dunlos before thoracoplastics caused by hereditary chest deformation and by impairments of cardiovascular system. PMID- 2905847 TI - [Electron microscopic immunohistochemistry in the diagnosis of human lymphotropic viral diseases]. AB - Immunohistochemistry is finding an ever increasing application for electron microscopic diagnosis of human viral diseases. Certain progress has been made in the use of peroxidase-DAB/OsO4 as an electron-dense marker, and colloid gold. The paper discusses immunohistochemistry application for electron microscopic detection of such lymphotropic viruses as VSV (virus of vesicular stomatitis cultured in mink's lung cells), HTLV-1 (virus of human T4-cell C91Pl lymphoma culture) and HTLV-III/HIV-1 (virus growing in human T4-cell H9 culture). PMID- 2905848 TI - [Loading tests in assessing the treatment of patients having had a myocardial infarct]. PMID- 2905850 TI - [Selected contributions on the history of pediatric endocrinology. 4: Congenital cryptorchism]. PMID- 2905849 TI - [Effect of temperature on the infectivity of the iridovirus and densonucleosis virus of blood-sucking mosquitoes]. AB - Mosquito densonucleosis virus and iridovirus were used to study the influence of temperature on their infectivity. Biological assays of mosquito densonucleosis virus were carried out in larvae of I-II instar of Aedes aegypti mosquitoes, those of mosquito iridovirus in larvae of Galleria mellonella. The rate of inactivation was found to be directly dependent on the dose of the heat treatment. Treatment at 60 degrees C led to complete loss of iridovirus infectivity; the virus activity declined considerably after treatment at 50 degrees and 40 degrees C for 60 min. Mosquito densonucleosis virus infectivity was eliminated completely at 65 degrees C. The decline of infectivity of both viruses was intermittent. PMID- 2905851 TI - [Urinary enzyme diagnosis--a suggestion for the definition of preanalytic conditions]. PMID- 2905852 TI - [Max Wertheimer in Frankfurt--on the origin and development crisis of gestalt psychology. III. Further studies of motion perception (1929-1933)]. PMID- 2905854 TI - Opposing the direct and the indirect theory in explaining the tunnel effect. PMID- 2905853 TI - [Wolfgang Kohler, gestalt psychology and the "natural philosophy" of gestalt. On the 100th anniversary of the birthday of the co-founder of the Berlin school]. PMID- 2905855 TI - [The public sectors show themselves]. PMID- 2905856 TI - [Complex treatment of patients with eczema including acupuncture]. PMID- 2905857 TI - A new type of fimbriae on Salmonella typhimurium. PMID- 2905858 TI - [The cortical layer of the cytoplasm--a possible site of the action of prenervous transmitters]. AB - Specific and opposite effects of some transmitter antagonists (beta adrenoblockers, serotonin antagonists) on mechanical properties of the surface of fertilized eggs of the sea urchin Paracentrotus lividus have been demonstrated. Possible role of endogenous transmitters in regulation of the properties of cytoplasmic cortex is discussed. PMID- 2905859 TI - [Mechanisms of the interaction of neurotransmitter systems]. AB - Interaction between different neurotransmitter systems has been revealed on various objects--the myocardium, identified, intact and internally perfused isolated neurons of molluscs. In frog myocardium, the inhibitory effect of adrenaline on cholinergic response may be simulated by theophylline and cholera toxin, i.e. the substances which indirectly increase intracellular content of cAMP. Another interaction reaction--inhibition of the response to adrenaline by acetylcholine--may be reproduced by imidazole, which decreases cAMP content due to activation of phosphodiesterase. Two types of interaction between serotonin and acetylcholine were revealed in the identified neurons of the snail Helix pomatia. In some of the neurons, serotonin increases acetylcholine depolarization, whereas in other ones decreases the latter. Both the increase and the decrease of responses to acetylcholine may be reproduced by theophylline. On intracellularly perfused neurons of Lymnaea stagnalis, modulation of acetylcholine responses of cell by biogenic amines was observed, the effect being induced by the drugs added not only to the surface membrane, but to intracellular medium as well. PMID- 2905860 TI - [Infection caused by the human immunodeficiency virus type 2 in the USSR]. AB - The serological study of 20 sera, showing atypical reaction with HIV-1 in the immunoblotting assay, for the presence of HIV-2 infection revealed some cases of this infection among Africans who had arrived to the USSR from Western Africa (5 cases) and Burundi (1 case); besides, in 1 case HIV-2 infection was detected in a Soviet female citizen having had many sexual partners among foreigners. PMID- 2905861 TI - [Towards the 4th All-Union congress of neurosurgeons]. PMID- 2905862 TI - A modified cytochemical method for DAP IV demonstration which enables simultaneous visualization of cell surface immunostaining. PMID- 2905863 TI - Drug-related dizziness. AB - Various causes of drug-related dizziness are reviewed. Several medical agents, such as antianxiety drugs, tricyclic antidepressants, antihypertensive drugs, antituberculous drugs, polypeptide antibiotics, local anaesthetics and non steroidal anti-inflammatory drugs, are known to produce dizziness as a side effect. PMID- 2905864 TI - Bradykinin activates peripheral capsaicin-sensitive fibres via a second messenger system. AB - A preparation of the neonatal rat spinal cord with attached tail was maintained in vitro and was used to study the mechanism of action of bradykinin on peripheral nociceptors. Spinal ventral root depolarization was used as an index of peripheral fibre activation. Capsaicin-sensitive fibres in the tail were activated by bradykinin and a phorbol ester. The protein kinase C inhibitor staurosporine attenuated the effect of bradykinin and phorbol. [Des-Arg9] bradykinin was inactive but bradykinin responses were reversibly antagonized by D Arg0-Hyp2-Thi5,8-D Phe7-bradykinin. These data suggest that bradykinin activates nociceptors via a bradykinin B2-receptor coupled to protein kinase C. PMID- 2905865 TI - The effect of L-glutamic acid on airway function and reactivity in the rabbit. AB - The ingestion of monosodium glutamate in sensitive individuals has been reported to cause severe asthma. We therefore studied the effects of L-glu on airway function and histamine (H) responsiveness in the rabbit. Histamine dose response curves (HDR's) were performed by measuring total lung resistance (RL) after inhalation of saline and increasing concentrations of H (1-30 mg/ml). The concentration of H producing a 20% increase in RL (PC20H) was obtained by interpolation. To assess the effects of L-glu, 8 rabbits were infused with L-glu (0.2 g/kg/hr) or saline in random order (14 days apart) for 4 hours followed by an HDRC. To look at possible late effects, a repeat HDRC was also performed in 6 rabbits 12 hours after completion of the L-glu infusion. In order to see whether rabbits rendered hyperresponsive responded to L-glu, the above protocol was performed in 7 rabbits following the inhalation of 3 micrograms of the activated complement fragment C5a des Arg. The L-glu infusions increased the plasma levels approx. ten-fold (mean +/- SEM 0.119 +/- 0.012 base-line, 1.272 +/- 0.061 mmol/l post infusion). L-glu did not increase the PC20H or baseline RL in either the normal rabbits at 4 or 12 hours or in the C5a des Arg treated rabbits at 4 hours. It is concluded that L-glu does not cause bronchoconstriction or an increase in airway responsiveness to H in the rabbit. PMID- 2905866 TI - Histamine H2-receptor blocking activity of ranitidine and lamtidine analogues containing aminomethyl-substituted aliphatic systems. AB - The possibility that the aromatic component in the classical H2-antagonists might not be essential for histamine H2-receptor blockade has been investigated. In the ranitidine series the removal of the furan ring is accompanied by a drastic decrease in H2-blocking activity, but not by its disappearance (compound HB5:KB on guinea pig isolated atria 31.6 microM) whereas in the lamtidine analogues the substitution of the phenyl moiety with the more reduced pi-bonded CH3-C = N-area generates a compound whose activity is comparable to that of cimetidine (KB on atria 1.12 microM; ID50 in the lumen-perfused stomach of the anaesthetized rat 3.61 mumol/kg i.v.). The results also indicate that the diaminofurazan group confers high affinity at the histamine H2-receptor. It is concluded that the aromatic portion of H2-antagonists related to ranitidine and lamtidine is not a minimal requisite for activity when an appropriate polar group is used as an "urea equivalent" moiety. PMID- 2905868 TI - Hypnotic desensitization of job-related heat intolerance in recovered burn victims. PMID- 2905867 TI - The effects of beta-adrenergic receptor agonists on the H2O2 formation in alveolar macrophage suspensions are not mediated by beta-receptors. AB - In the present study, the effects of beta-adrenergic receptor agonists on the hydrogen peroxide (H2O2) production in phorbol myristate acetate stimulated guinea pig alveolar macrophage suspensions have been investigated. In contrast to suggestions described in literature, our results indicate that the H2O2 production in alveolar macrophage suspensions is not mediated by beta-adrenergic receptors. Rather, it is suggested that the inhibitory effect of catecholamines in the H2O2 formation which is found after 5 minutes is the result of inhibition of the horseradish peroxidase catalysed phenol red oxidation, used as H2O2 measurement, by the catecholamines. PMID- 2905869 TI - Cardiovascular risk factors and antihypertensive therapy. AB - Reduction of elevated blood pressure is effective in reducing morbidity and mortality from cardiovascular disease in general. Striking decreases in stroke, congestive heart failure, and renal impairment have been observed when blood pressure is reduced. However, the ability of traditional, diuretic-first, stepped care therapeutic algorithms to reduce the occurrence of myocardial infarction or angina has been exceedingly difficult to demonstrate. An increased frequency of sudden death among hypertensive men with electrocardiographic abnormalities has been observed in some diuretic-based treatment trials. The failure of conventional therapy to reduce coronary artery disease and death has forced a re appraisal of antihypertensive treatment. The risk factors for coronary disease are reviewed in detail with an emphasis on the impact of various classes of antihypertensive drugs on these factors. The emergence of effective antihypertensive agents that lower blood pressure without adversely affecting cardiovascular risk factors provides a new opportunity to further extend the benefit of treatment by reducing such risk. PMID- 2905870 TI - [Changes in the reproductive potentials of rat progeny treated during pregnancy with alcohol, diazepam, medazepam and their combinations]. PMID- 2905871 TI - Prader-Willi syndrome. PMID- 2905872 TI - Simultaneous determination of glafenine and floctafenine in human plasma using high-performance liquid chromatography. AB - A high-performance liquid chromatography (HPLC) assay has been developed for the determination of glafenine and floctafenine in plasma. Drugs are extracted with ethyl acetate from alkalinized samples using antipyrine as an internal standard. After evaporating the solvent to dryness, the residue is removed and analyzed using a microPorasil 10 micron column with a mobile phase of n-hexane and ethanol (80/20, v/v). The drugs are detected at 240 nm. The lower detection limits are 1.993.10(-2) mumol/l and 3.138.10(-2) mumol/l for glafenine and floctafenine, respectively. The method is simple, rapid and very sensitive. It is the first HPLC method for the determination of floctafenine. PMID- 2905873 TI - [Coexistence of acetylcholine and calcitonin gene-related peptides at the frog neuromuscular junction: a model for the study of differential secretion of classical neurotransmitters and peptides]. PMID- 2905874 TI - [Prenatal diagnosis of mucoviscidosis using biochemical analysis of the amniotic fluid. Evaluation at the University Hospital Center of Rennes]. PMID- 2905875 TI - Therapeutic applications of drugs acting on alpha-adrenoceptors. AB - For over a decade it has been known that clonidine and alpha-methyldopa lower blood pressure by activating central and peripheral alpha-2-adrenoceptors and prazosin likewise by antagonizing alpha-1-adrenoceptors. During the 1980s, the number of therapeutic indications for drugs which act via these classes of alpha adrenoceptors has expanded greatly, particularly the non-cardiovascular applications of drugs acting on alpha-2-adrenoceptors. Novel alpha-2-agonists such as detomidine and medetomidine have been introduced into veterinary medicine as sedative/analgesics. It is possible that these and other compounds with better alpha-2-adrenoceptor selectivity than clonidine may be used in human medicine to ease symptoms of anxiety in drug- and alcohol-related withdrawal syndromes, and as preanaesthetic agents. Several novel alpha-2-adrenoceptor antagonists, such as idazoxan and atipamezole, have been developed with improved selectivity compared to the traditional antagonist at these receptors, yohimbine. At present none of these new compounds are registered for use, but several are undergoing clinical trials for a variety of therapeutic applications such as depression (idazoxan), arousal of animals sedated with alpha-2-agonists (atipamezole), and adult-onset diabetes (DG-5128). The established use of yohimbine in the treatment of male sexual impotence has been reconfirmed and several of the above compounds may be evaluated in the future to treat this disorder. PMID- 2905876 TI - Beta-adrenoceptor changes in blood lymphocytes and altered drug responsiveness. PMID- 2905877 TI - Differences in betablocking drugs in cardiovascular therapy. AB - Clinically significant differences between various beta-adrenoceptor blocking drugs exist. Patients with ischaemic heart disease and exertional angina pectoris benefit from all types of beta-blockers. Drugs with intrinsic sympathomimetic action (ISA) given intravenously may be safer in some patients with acute myocardial infarction than those drugs without ISA. In cardiac patients at rest they may have a vasodilator action and cause less myocardial depression than beta blockers without ISA. When, however, the cardiac sympathetic tone is high pindolol and other beta-blockers with ISA act as any other beta-blockers, producing haemodynamic impairment. Studies have shown that beta-blockers with ISA confer less benefit in secondary prevention after myocardial infarction and they are not suitable for the treatment of obstructive cardiomyopathy. Non-selective beta-blockers may be advantageous in hypokalaemic arrhythmias. Beta 1-blockers may be preferred for patients with bronchoconstriction, diabetes, peripheral vascular disease and, theoretically to some extent in theory also in patients with hypertension. The extent and nature of side effects may also influence the selection of the most suitable beta-blocker in cardiovascular therapy. PMID- 2905878 TI - Dopamine receptors and psychiatric drug treatment. AB - The established antipsychotic drugs act mainly by antagonizing dopamine mediated synaptic transmission in the brain. Increase in the rate of production of dopamine metabolites as well as the firing rate of dopamine-containing neurons can be interpreted as compensatory responses to an interruption of synaptic transmission at dopamine nerve terminals. The demonstration of involvement of limbic and cortical mechanisms in the antipsychotic activity of neuroleptic drugs is far more difficult than the involvement of nigro-striatal and tubero infundibular mechanisms in the neurological and neuroendocrine effects of these drugs. Application of radioreceptor techniques to dopamine research has supported the findings obtained by other neuropsychopharmacological research techniques, providing more direct evidence of dopamine receptor blockade by neuroleptic drugs. Further research is needed especially in studying the nature of the time dependent adaptive changes at the receptor sites as well as the differences between the different dopamine projections and neural systems in the brain. The different subtypes of dopamine receptors in the brain, currently called D1 and D2 dopamine receptors, seem to be parallel, although in many respects independently acting regulatory systems. Dopamine D2 receptor-selective antagonists such as sulpiride seem to cause selective D2 receptor up-regulation. Prolactin secretion seems to be regulated by D2 dopamine receptors. The exact physiological role of D1 dopamine receptors as well as the clinical consequences of selective D1 antagonism is not known. Sulpiride and clozapine are examples of atypical neuroleptic compounds that have quite different profile of action, the former having strong and selective antidopaminergic action, the latter combining a number of non- dopaminergic mechanisms with rather slight effects on dopamine receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2905879 TI - Haemodynamic effects of atenolol and bopindolol at rest and during isometric exercise. A non-invasive study in healthy volunteers. AB - Circulatory effects of bopindolol, a new nonselective beta blocking agent with intrinsic sympathomimetic activity and atenolol were compared. After baseline and first dose measurements atenolol 25 mg twice daily and bopindolol 1 mg daily were given to 10 healthy young subjects. Haemodynamic measurements were made noninvasively using echocardiography and systolic time intervals. Clinical and circulatory indices were measured at baseline, after initial dose and after one week of regular treatment at rest and at isometric handgrip exercise (IE) (HG). Atenol reduced the heart rate from 62 bpm to 49 and blunted totally the HR increase during IE (p less than 0.01). Bopindolol caused a 10% fall in heart rate (NS) at rest and a 15% fall (p less than 0.05) during IE. BP fell by 6% after atenol administration and 4% after bopindolol (NS) at rest and similarly during IE. In contrast to bopindolol, atenolol caused small increases initially in left ventricular end-diastolic dimension (LVEDD) and left ventricular end-systolic dimension (LVESD). A 10% increase in FS was seen at rest after bopindolol administration (NS). With the fall in heart rate the estimated cardiac output (CO) also fell from 3.66 to 3.151/min (P less than 0.05) after atenolol but rose from 3.87 to 3.93 after bopindolol (NS) during chronic treatment. Consecutively the total peripheral resistance (TPR) was increased to some extent by atenolol, whereas bopindolol reduced it at rest and during IE. A similar response was also found in systolic time intervals PEP/LVET which were reduced during bopindolol administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2905880 TI - Duplication of HRAS1, INS, and IGF2 is not a common event in Beckwith-Wiedemann syndrome. AB - A few cases of Beckwith-Wiedemann syndrome (BWS) have in common a duplication of 11p15. Among the genes located in 11p15, c-Ha-ras 1 (HRAS1), insulin (INS), and insulin-like growth factor II (IGF2) may account for the clinical features and the increased risk for malignancy. Using eight 11p15 markers including HRAS1, INS and IGF2 we have studied eight sporadic and hereditary cases of BWS whether or not associated with a nephroblastoma. By gene dosage determination and family studies, we have shown the following: the eight patients examined had an apparent diploid representation of all of the eight markers studied, thus indicating that a microduplication of these markers or of the region characterized by these markers is not a common event in BWS; in a family with three affected sibs the genes for HRAS1 and INS/IGF2 did not cosegregate with BWS and therefore may not participate in the pathogenic processes here observed. PMID- 2905881 TI - Effect of H2 antagonists cimetidine and famotidine on the hemotoxicity of cyclophosphamide. AB - A comparison between the effects of H2 antagonists Cimetidine and Famotidine on the hemotoxicity of Cyclophosphamide in vivo in DBA/2NCrBl mice is described. Hemotoxicity of anticancer drug was determined by peripheral blood leukocytes, bone marrow cells and bone marrow CFU-S, GM-CFC. Results show that Famotidine does not increase Cyclophosphamide hemotoxicity while Cimetidine enhances the toxicity of the anticancer drug only on normal pluripotent hemopoietic stem cells. PMID- 2905882 TI - In vivo requirement for asialo GM1 and Thy1 positive leukocytes for antitumor effect of rIL-2 +/- rIFN-gamma. AB - Localized treatment with recombinant human interleukin-2 (rIL-2) +/- recombinant murine interferon-gamma (rIFN-gamma) results in regression of early B16 melanomas in normal C57BL/6 (B6) mice, but not in syngeneic beige mice, which have defective natural killer (NK) cells. Injection of antibodies to asialo GM1 (a AGM1) or Thy1 abolishes the tymoricidal effects of rIL-1 +/- rIFN-gamma. Thus, cells activated by these cytokines must be either NK-like cells that are AGM1+ Thy1+, or NK-like cells (AGM1+) cooperating with T lymphocytes (Thy1+), since either antibody (a-AGM1 or a-Thy1) independently abrogates the in vivo antitumor effect. PMID- 2905883 TI - Inhibition by retinoids of in vitro invasive ability of human lung carcinoma cells. AB - The effect of retinoid treatment of A549 human lung carcinoma cells on in vitro cell invasion using the human amnion basement membrane (BM) was investigated. A 2 day retinoid pretreatment of the cells resulted in a significant reduction in their invasive ability. The most effective retinoid, retinol acetate, inhibited cell migration through the BM and degradation of [3H] proline labeled BM components by 50% at noncytotoxic concentrations of 0.09, and 3 micrograms/ml, respectively. Inhibition by retinol acetate of A549 cell invasive potential was accompanied by a significant decrease in type IV collagenase activity and no change in transglutaminase activity. PMID- 2905884 TI - [Breast-feeding and intestinal parasites]. AB - The extent of intestinal parasitic infection was determined using 4 methods of fecal examination in 400 Gabonese infants aged 0.5 to 24 months (86 exclusively and 151 partially breast-fed and 163 artificially fed) and in 170 of their mothers in an African urban community. Parasitic prevalence was the same in the stools of the mothers from the 3 infant groups, providing evidence for the same level of exposure to parasites in all infants. Exclusively and partially breast fed infants excreted parasites in numbers significantly lower than artificially fed infants of the same ages, during the first and the second years of life. This antiparasitic activity of human milk concerned mostly Giardia and ascaris, was not exclusively due to a decreased exposure to parasites in breast-fed infants and did not seem exclusively antibody-mediated; the role of lipids is possible. PMID- 2905885 TI - [Acute cardio-respiratory failure after niaprazine absorption]. PMID- 2905886 TI - [Positive inotropic acting compounds. II. Synthesis 5- and 6-substituted phenanthridines and the mechanism of their positive inotropic action]. PMID- 2905888 TI - [Myocardial revascularization and internal mammary artery. Current status]. PMID- 2905887 TI - [Lactones. 19. The structure and pharmacology of gamma-lactone-bridged diphenylalkylamine]. PMID- 2905889 TI - Esophageal candidiasis and immunodeficiency associated with acute HIV infection. PMID- 2905890 TI - [Single blind trial with domperidone in orally soluble granulates in patients with functional dyspepsia treated with H2 blockers]. PMID- 2905891 TI - Studies on urinary gamma-glutamyl transpeptidase in nephrotic syndrome patients. AB - (1) Variations in the levels of GGT were measured in urine specimens taken in the early morning in control and in 20 consecutive adult patients with uncomplicated nephrotic syndrome. (2) The urinary GGT activity was increased in all cases of nephrotic syndrome patients investigated with different etiology. (3) A significant correlation was found between urinary GGT activity and serum albumin (r = 0.727) but not with serum cholesterol (r = 0.129). (4) These findings suggest that enhanced excretion of urinary GGT may be stimulated by decreased albumin concentration or oncotic pressure but does not appear to be due to leakage from plasma. (5) A systematic study on urinary GGT showed that GGT activity was decreased to the upper limit of normal control values in nephrotic syndrome patients after remission. PMID- 2905892 TI - Decline in CD4+ cell numbers reflects increase in HIV-1 replication. AB - Changes in CD4+ cell numbers were studied in relation to the presence of HIV-1 antigen (HIV-1-Ag) in serum from homosexual men followed prospectively. During 30 months of follow-up the mean CD4+ cell number (x 10(9) per liter) was stable in 134 at entry HIV-1 antibody (HIV-1-Ab) seropositives, who remained HIV-1-Ag negative (from 0.59 to 0.62) and declined in 38 at entry HIV-1-Ab seropositives who were persistently HIV-1-Ag positive (from 0.43 to 0.34). In sera of 9 of 65 HIV-1-Ab seroconverters HIV-1-Ag was detected only once, 3 months before or concomitantly with antibody seroconversion. Another 11 men became persistently HIV-1-Ag positive with antibody seroconversion or 2-6 weeks thereafter. A decline in CD4+ cell numbers was seen between 6 months before and the moment of HIV-1-Ab seroconversion, independently of duration and level of antigen expression. This indicates initial HIV-1 replication in both HIV-1-Ag negatives and positives. Following antibody seroconversion, HIV-1-Ag negatives had higher CD4+ cell numbers than HIV-1-Ag positives. Similarly to those who were HIV antigenemic from entry of the study, the HIV-1-Ab seroconverters who concomitantly with seroconversion or shortly thereafter became HIV-1 antigenemic showed a steady and significant (p = 0.01) decline in CD4+ cell numbers. In those who remained HIV-1 Ag negative after antibody seroconversion, CD4+ cell numbers were stable during follow-up.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2905893 TI - Intracerebroventricular infusion of dopamine and its agonists in rodents and primates. An experimental approach to the treatment of Parkinson's disease. AB - The authors investigated the effects of chronic intracerebroventricular (ICV) infusion of dopamine (DA) and DA agonists in animal models of DA deficiency in rodents and primates. Rats with unilateral nigrostriatal lesions induced by 6-OH DA received infusions of DA, pergolide, lisuride, and (+)-4-propyl-9 hydroxynaphthoxacine (PHNO) for from 1 to 2 weeks through a catheter implanted into the cerebral ventricle ipsilateral to the lesion and connected to an osmotic minipump filled with the active substance. The infused animals had persistent contralateral rotation during the period of infusion. The DA infusion restored DA levels in lesioned animals. In animals treated chronically with reserpine, the ICV DA infusion restored DA levels in the brain, but akinesia was not reversed unless monoamine oxidase inhibiters were also given, intraperitoneally or ICV, with the DA infusion. An ICV infusion of PHNO reversed reserpine-induced akinesia. The infusion of DA or PHNO restored normal patterns of behavior in monkeys made akinetic by treatment with 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP), but the infusion was complicated by intolerance to the pump or frequent disconnection of the catheter. An ICV infusion of PHNO may be an alternative experimental approach to the treatment of fluctuations in patients with Parkinson's disease. PMID- 2905894 TI - Spectral properties of fluorescent derivatives of the oligomycin sensitivity conferring protein and analysis of their interaction with the F1 and F0 sectors of the mitochondrial ATPase complex. AB - In order to study the kinetics and the nature of the interactions between the oligomycin sensitivity conferring protein (OSCP) and the F0 and F1 sectors of the mitochondrial ATPase complex, fluorescent derivatives of OSCP, which are fully biologically active, have been prepared by reaction of OSCP with the following fluorescent thiol reagents: 6-acryloyl-2-(dimethylamino)naphthalene (acrylodan), 2-(4-maleimidylanilino)naphthalene-6-sulfonic acid (Mal-ANS), N-(1 pyrenyl)maleimide (Mal-pyrene), 7-(diethylamino)-3-(4-maleimidylphenyl)-4 methylcoumarin (Mal-coumarin), and fluorescein 5-maleimide (Mal-fluorescein). The preparation of these derivatives was based on the previous finding that the single cysteinyl residue of OSCP, Cys 118, can be covalently modified by alkylating reagents without loss of biological activity [Dupuis, A., Issartel, J. P., Lunardi, J., Satre, M., & Vignais, P. V. (1985) Biochemistry 24, 728-733]. For all fluorescent probes used, except Mal-pyrene and Mal-fluorescein, the emission spectra of conjugated OSCP were blue-shifted relative to those of the corresponding mercaptoethanol adducts, indicating that the fluorophores attached to Cys 118 were located in a hydrophobic pocket. These results were consistent with the high quantum yields and the increased fluorescence lifetimes of conjugated OSCP compared to mercaptoethanol adducts in aqueous buffer. They also fit with quenching data obtained with potassium iodide which showed that the fluorophore is shielded from the aqueous medium when it is attached to Cys 118 of OSCP. Especially noticeable was the wide half-width of the OSCP-acrylodan emission peak compared to that of mercaptoethanol-acrylodan.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2905895 TI - Regulation of growth hormone release in fetal calves. AB - Plasma GH and IGF1 concentrations were measured during the last 2 months of gestation in 9 chronically catheterized fetal calves under basal conditions or following growth-hormone-releasing factor (GRF), thyrotropin-releasing hormone (TRH) or SRIF intravenous cotyledonnary injections. Plasma GH concentrations were higher in fetuses (1.40 +/- 0.10 nmol/l) than in dams (0.14 +/- 0.01 nmol/l). Plasma GH secretory profile was pulsatile. The number of secretory pulses, as well as their magnitude and mean baseline values decreased from 220 to 270 days of gestation. Synthetic 1-29 GRF or TRH increased fetal plasma GH concentration at 250 and 270 days of gestation but was devoid of any significant effect at 220 days. SRIF injection decreased plasma GH concentration in 270-day-old fetuses. Plasma IGF1 concentrations were lower in fetuses than in dams. No treatment had a significant effect on fetal and maternal IGF1 levels. PMID- 2905896 TI - Beta blockers inhibit fetal thromboxane A2 production in vitro. AB - The effects of beta-blocking propranolol, metoprolol, atenolol and labetalol on the production of the proaggregatory and vasoconstrictive thromboxane A2 (TxA2) by fetal platelets were studied. To this end, umbilical blood samples were allowed to clot in the absence or presence of various concentrations of these agents, and the release of TxB2 (a metabolite of TxA2) was measured. Propranolol and labetalol inhibited TxA2 production in 0.1-mmol concentrations and metoprolol and atenolol in 1-mmol concentrations. The required concentration was always higher than could be achieved by peroral treatment. Beta blockers may have this effect through phospholipase A2 because the conversion of exogenous arachidonic acid to TxB2 was not affected except in the case of propranolol, which inhibited slightly TxB2 formation from exogenous arachidonic acid. PMID- 2905897 TI - Maintenance treatment with H2 receptor antagonists in patients with peptic ulcer disease: reduces morbidity in a significant minority of patients. PMID- 2905898 TI - Maintenance treatment with H2 receptor antagonists in patients with peptic ulcer disease: rarely justified in terms of cost or patient benefit. AB - Maintenance treatment reduces the frequency of ulcer relapse. Its routine use is unnecessary because the condition is benign and most patients do not relapse frequently. Routine maintenance treatment does not reduce the incidence of complications of ulcers overall, although it may do so in specific groups mentioned above. Routine maintenance treatment for all patients with ulcers would be expensive as well as largely unnecessary. PMID- 2905899 TI - Misuse of temazepam. PMID- 2905900 TI - Effects of non-sedative anxiolytic drugs on responses to GABA and on diazepam induced enhancement of these responses on mouse neurones in cell culture. AB - 1. Intracellular microelectrode recording techniques were performed on mouse spinal cord and cerebral hemisphere neurones grown in primary dissociated cell culture. The effects of several anxiolytics applied by local pressure ejection on responses to gamma-aminobutyric acid (GABA) evoked by iontophoresis were investigated. Responses to GABA were depolarizing since intracellular chloride ion concentration was increased by injection from potassium chloride (3M)-filled recording micropipettes and neurones were held at large negative membrane potentials (-70 to -90 mV). The agents studied were six 'non-sedative anxiolytics', CL 218,872 (3-methyl-6-(3-trifluoromethyl-phenyl)1,2,4-triazolo(4,3 b) pyridazine), PK 8165 (2-phenyl-4-(2-(4-piperidinyl)ethyl)-quinoline), PK 9084 (2-phenyl-4-(2-(3-piperidinyl)ethyl)-quinoline), CGS 9896 (2-(4-chlorophenyl)-2,5 dihydropyrazolo(4,3-c)quinoline-3(3H)-one) , ZK 91296 (ethyl 5-benzyloxy-4 methoxymethyl-beta-carboline-3-beta-carboxylate), buspirone (8-4-[4-(2 pyrimidinyl)-1-piperazinyl]butyl-8-azaspiro[4.5]decane- 7,9- dione), and two sedative anxiolytics, diazepam and zopiclone [( 6-(5-chloro-2-pyridyl)-6,7 dihydro-7-oxo-5H-pyrrolo[3,4-b]pyrazin- 5- yl]4-methyl-1-piperazinecarboxylate). 2. Direct effects on responses to GABA were studied for all drugs applied in varying concentrations. For the drugs which significantly altered responses to GABA, the effects of the benzodiazepine receptor antagonists Ro 15-1788 (ethyl-8 fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo(1,5a)-(1,4)benzodi azepine - 3 carboxylate) and CGS 8216 (2-phenylpyrazolo(4,3-c)-quinolin-3(5H)-one) were evaluated. For the drugs devoid of significant direct effect on responses to GABA, the influence on diazepam-induced enhancement of responses to GABA was evaluated. 3. Diazepam, zopiclone and CL 218,872 concentration-dependently and reversibly enhanced responses to GABA. Maximal enhancement was 82% for diazepam (500 nM), 64% for zopiclone (10 microM) and 20% for CL 218,872 (10 microM). PK 8165 effects varied with concentration, enhancing responses to GABA (up to 18%) at nM concentrations and reducing responses to GABA (up to 90%) at microM concentrations. CGS 9896, ZK 9126, PK 9084 and buspirone, in concentrations ranging from 1 nM to 10 microM, lacked significant direct effects on responses to GABA. 4. The enhancing effects of diazepam, zopiclone, CL 218,872 and PK 8165 were antagonized by Ro 15-1788. However, the reducing effect on responses to GABA of PK 8165 at microM concentrations was not antagonized by CGS 8216. CGS 9896 and ZK 91296 concentration-dependently blocked the diazepam-induced enhancement of responses to GABA. However, PK 9084 and buspirone did not antagonize the diazepam induced enhancement of responses to GABA. 5. These results indicate that diazepam and zopiclone may be full agonists, CL 218,872 and PK 8165 are partial agonists, and CGS 9896 and ZK 91296 are pure antagonists at benzodiazepine receptors. On the other hand, PK 9084 and buspirone do not interact with benzodiazepine receptors. PMID- 2905901 TI - Antinociception and physical dependence produced by [D-Arg2] dermorphin tetrapeptide analogues and morphine in rats. AB - 1. The antinociceptive effects of [D-Arg2] dermorphin tetrapeptide analogues, H Tyr-D-Arg-Phe-Gly-NH2 and H-Tyr-D-Arg-Phe-beta-Ala-OH when administered subcutaneously (s.c.) in rats were measured by the tail-flick test. In addition, the appearance of typical withdrawal signs upon cessation of administration or on subsequent treatment with naloxone were measured after chronic administration of either peptide or morphine. 2. The dose of peptides and of morphine in the physical dependence test was determined from the AD50 to inhibit the tail-flick test in rats. Doses from 4 to 64 times the AD50 doses were employed in the s.c. administration schedules. 3. The intensity of the antinociception induced by either peptide was greater than that produced by morphine. Moreover, the antinociception induced by the peptides was of much longer duration than that produced by morphine. 4. Abrupt withdrawal after chronic administration of either peptide produced only slight loss of body weight. In contrast, morphine withdrawal produced sharp loss of body weight. 5. Naloxone precipitated withdrawal signs after chronic administration of either peptide were less intense than those after chronic morphine. 6. These results suggest that the antinociception produced by these peptides is more intense and of longer duration than that produced by morphine. It is also interesting to note that the physical dependence produced by these peptides is less marked than that produced by morphine. PMID- 2905902 TI - Possible mechanism of acetaldehyde-induced noradrenaline release from sympathetic nerve terminals in isolated blood vessels. AB - 1. Vasoconstrictor responses to acetaldehyde were investigated in isolated and perfused canine intermediate auricular (ear) arteries. 2. Single injections of small doses of acetaldehyde (1-3 mumol) induced vasoconstriction in a dose related manner and showed no tachyphylaxis. On the other hand, large doses of acetaldehyde (10-30 mumol) frequently caused tachyphylaxis when injected at 10 min intervals. 3. After tyramine treatment, constrictions induced by a large dose of acetaldehyde were consistently restored temporarily. 4. The acetaldehyde induced vasoconstriction was inhibited by bunazosin, a potent alpha 1 adrenoceptor antagonist. 5. A small dose of imipramine blocked tyramine-induced vasoconstriction, but had no significant influence on noradrenaline (NA)-induced constrictions, and caused slight potentiation of acetaldehyde-induced constrictions. 6. Hydrocortisone treatment did not modify tyramine-induced vasoconstrictions and slightly suppressed NA- and acetaldehyde-induced constrictions but not significantly. 7. It is suggested that acetaldehyde causes a release of NA from a NA store of the sympathetic nerve terminals which is different from the tyramine-sensitive NA store, and that the acetaldehyde sensitive NA store may be readily filled up with NA from the tyramine-sensitive store. PMID- 2905903 TI - Palytoxin-induced contraction and release of endogenous noradrenaline in rat tail artery. AB - 1. The mechanism of the contractile effect of a potent marine toxin, palytoxin (PTX) on the rat isolated tail artery was examined. 2. PTX (10(-7) M) induced a contraction in the tail artery which was dependent on external Ca2+. This contraction was inhibited (by 75% or more) by 10(-6) M prazosin, 2.4 x 10(-5) M bretylium and 10(-4) M 6-hydroxydopamine (6-OHDA), and partially (by 40%) by 10( 5) M indomethacin. However, this contraction was not affected by 10(-6) M tetrodotoxin (TTX), 10(-6) M nifedipine or reserpine treatment. The PTX-induced contraction in reserpine-treated artery was partially inhibited by nifedipine and indomethacin but not by prazosin. 3. Transmural electrical stimulation induced a transient contraction which was dependent on external Ca2+. The contraction induced by electrical stimulation was inhibited by TTX, prazosin, bretylium, reserpine treatment and 6-OHDA but not by nifedipine or indomethacin. 4. PTX increased the release of noradrenaline from this artery. However PTX did not release noradrenaline from reserpine-treated arteries. PTX-induced noradrenaline release was only partially inhibited by TTX or by Ca2+-free solution. 5. These results suggest that PTX has pre- and postsynaptic effects in the rat tail artery. PTX may stimulate adrenergic nerves and release noradrenaline mainly by a TTX-insensitive and Ca2+-independent mechanism and partially by a TTX-sensitive and Ca2+-dependent mechanism. Further, PTX may also release prostaglandins and depolarize smooth muscle cell membrane to induce a contraction. PMID- 2905904 TI - Evidence for dopaminergic co-transmission in dog mesenteric arterial vessels. AB - 1. The overflow of dopamine and noradrenaline (NA) from the main trunk of the dog mesenteric artery and its proximal branches during prolonged depolarization (120 min) by K+ (52 mM) was quantified by high performance liquid chromatography with electrochemical detection. 2. K+-induced depolarization resulted in release of both dopamine and NA. The amount of NA released from both blood vessels declined progressively throughout the experiment. In the main trunk the same pattern of release was observed for dopamine, whereas in the proximal branches the overflow of dopamine increased throughout the experiment. 3. The addition of phentolamine (0.2 microM) to the perifusion fluid increased the overflow of both amines. In the presence of sulpiride (1 microM) the overflow of dopamine and NA was found to be increased in the proximal branches, but not in the main trunk. The addition of phentolamine to sulpiride caused a further increase in amine overflow in proximal branches, but not in the main trunk. 4. The addition of alpha-methyl-p-tyrosine (50 microM) to the perifusion fluid caused a decrease in the amounts of dopamine and NA released from both preparations. In alpha-methyl-p-tyrosine-treated preparations phentolamine increased amine overflow to the same extent as in experiments without tyrosine hydroxylase inhibition. The increasing effect of sulpiride on the overflow of dopamine and NA from the proximal branches was completely abolished after alpha-methyl-p-tyrosine. 5. The results presented suggest that in the proximal branches of the dog mesenteric artery, dopamine beta hydroxylase represents a rate limiting step in the synthesis of NA; dopamine, through activation of prejunctional dopamine receptors acts like a prejunctional co-transmitter in the control of transmitter release, but only newly-synthesized dopamine appears to be responsible for this effect. PMID- 2905905 TI - Pre- and post-junctional actions of procaterol, a beta 2-adrenoceptor stimulant, on dog tracheal tissue. AB - 1. The effects of procaterol, a beta 2-adrenoceptor agonist, on excitatory neuro effector transmission in the dog trachea were investigated and the findings were compared to those seen with isoprenaline, with microelectrode, double sucrose gap and tension recording methods. 2. Procaterol (10(-10)-10(-9) M) and isoprenaline (10(-9) M) had no effect on the resting membrane potential or on the input resistance of the smooth muscle cells of dog trachea. However with increased concentrations (greater than 10(-8) M), these agents hyperpolarized the membrane and decreased the input resistance of the membrane. 3. Procaterol (10(-10)-10(-7) M) and isoprenaline (10(-9)-10(-7) M) dose-dependently reduced the amplitude of the twitch contractions evoked by field stimulation in the combined presence of indomethacin (10(-5) M) and guanethidine (10(-6) M). In parallel with actions on twitch contractions, procaterol (10(-10)-10(-7) M) and isoprenaline (10(-9)-10( 7) M) reduced the amplitude of the excitatory junction potentials (e.j.ps), evoked by single pulse field stimulation in the dog trachea. 4. Procaterol (10( 8) M) had no effect on the post-junctional response of smooth muscle cells to exogenous acetylcholine (ACh) (10(-7)-10(-6) M). 5. Pretreatment with ICI-118551, a beta 2-adrenoceptor blocking agent, reduced the inhibitory action of procaterol on the amplitude of twitch contractions evoked by field stimulations in the dog trachea. 6. These results indicate that procaterol in low concentrations has a prejunctional action inhibiting the excitatory neuro-effector transmission in addition to a postsynaptic action, presumably by suppressing transmitter release from the vagus nerve terminals through beta 2-adrenoceptors in the dog tracheal tissue. The pre- and post-junctional actions of procaterol explain its potent bronchodilator effects in clinical use. PMID- 2905906 TI - Tricyclic antidepressants block N-methyl-D-aspartate receptors: similarities to the action of zinc. AB - 1. Using the radioligand [3H]-MK801, we have examined drug interactions with the phencyclidine recognition site of the N-methyl-D-aspartate receptor. 2. The tricyclic antidepressants desmethylimipramine and imipramine inhibited [3H]-MK801 binding with IC50 values of 7.4 and 22.5 microM, respectively. Other related tricyclic antidepressants and neuroleptics were also effective but less potent. 3. Desmethylimipramine, imipramine and chlorimipramine slowed the dissociation rate of [3H]-MK801 in a similar manner to Zn2+. Phencyclidine and related compounds had no effect on the dissociation rate of [3H]-MK801. 4. Desmethylimipramine, imipramine and ketamine also prevented the Ca2+ influx into cultured cortical neurones of the rat produced by N-methyl-D-aspartate. 5. As the actions of tricyclic antidepressants in this system are not competitive with respect to N-methyl-D-aspartate, glycine or MK-801, and as they slow the dissociation of [3H]-MK801, we conclude that tricyclic antidepressants may be acting at the Zn2+ recognition site on the N-methyl-D-aspartate receptor. PMID- 2905907 TI - Activation of a bradykinin receptor in peripheral nerve and spinal cord in the neonatal rat in vitro. AB - In an in vitro preparation of the neonatal rat spinal cord with attached tail, administration of bradykinin (Bk) to the spinal cord or to the tail produced depolarization of a ventral root (L3-L5). The effect of Bk at each site was selectively and reversibly antagonized by D-Arg [Hyp2, Thi5,8 D-Phe7]-Bk but could not be mimicked or antagonized by the B1-receptor ligands [des-Arg9]-Bk or Leu8[des-Arg9]-Bk, respectively. Peripherally evoked noxious responses produced by capsaicin or heat, were unaffected by either antagonist administered to the spinal cord. These data suggest that Bk-evoked responses in the spinal cord and at peripheral nociceptors were mediated via a receptor which by definition is of the B2-type. Additionally Bk is unlikely to be a physiological mediator of acute nociception in the spinal cord. PMID- 2905908 TI - N,N-diallyl-tyrosyl substitution confers antagonist properties on the kappa selective opioid peptide [D-Pro10]dynorphin A(1-11). AB - 1. In the search for kappa-opioid antagonists, we have designed two N,N-diallyl substituted analogues of the kappa-selective peptide [D-Pro10]dynorphin A (1 11)(DPDYN). In this study, we have examined (i) the binding properties of N,N diallyl-DPDYN (analogue 1) and N,N-diallyl-[Aib2,3]DPDYN (analogue 2) at the three main types (mu, delta, kappa) of opioid binding sites, (ii) their binding sensitivity to Na+ ions (120 mM NaCl) and guanine nucleotide (50 microM Gpp(NH)p) at mu- and kappa-binding sites and (iii) their biological activity in two pharmacological bioassays specific for mu- and kappa-(guinea-pig ileum) and kappa (rabbit vas deferens) opioid receptors. 2. Steric hindrance resulting from incorporation of two bulky allyl groups at the tyrosal nitrogen atom greatly altered the binding properties of DPDYN. A dramatic fall in apparent affinity for the three types (mu, delta, kappa) of site as well as selectivity for kappa-sites was observed for the two N,N-diallyl-substituted peptide analogues. 3. At kappa sites of guinea-pig cerebellum and mu-sites of rabbit cerebellum, N,N-diallyl substitution led to a complete loss of binding sensitivity to the inhibitory effect of 120 mM NaCl + 50 microM Gpp(NH)p compared to the high sensitivity of DPDYN. This may therefore suggest that the N,N-diallyl-DPDYN analogues are endowed with opioid antagonist properties. 4. No agonist activity of the analogues was observed in guinea-pig myenteric plexus and rabbit vas deferens organ preparations. In contrast, both of the diallyl-substituted peptides displayed similar antagonist properties against the kappa-agonist DPDYN in both preparations. In the guinea-pig ileum, the affinities of the antagonist peptides against the mu-agonist Tyr-D-Ala-Gly-MePhe- NH(CH2)20H(DAGOL) were approximately half that observed against DPDYN. 5. These results show that N,N-diallyl-tyrosyl substitution leads to analogues of DPDYN which act in vitro as pure opioid antagonists and exhibit a reasonable affinity at, but a weak selectivity for, the K-opioid receptors. PMID- 2905909 TI - Complex interactions of agonists with alpha 1-adrenoceptors in intact cells. AB - 1. The apparent Ki values of (-)-noradrenaline (NA), (+)- and (-)-adrenaline (Ad), phenylephrine and the mono-fluorinated NAs (in position 2, 5 or 6) for alpha 1-adrenoceptors of intact BC3H1 cells labelled with [3H]-prazosin were greatly dependent on the incubation temperature. 2. The EC50 values of these compounds for stimulation of the inositol phosphate (IP) accumulation at 37 degrees C were intermediate between their apparent dissociation constants at 2 degrees C (Ki2 degrees) and at 37 degrees C (Ki37 degrees). 3. The fact that an irreversible blockade of 46% +/- 6% (n = 3) of the [3H]-prazosin binding sites by phenoxybenzamine reduced the maximal IP-formation induced by NA by 57% +/- 5% (n = 3) shows that there is a direct coupling between alpha 1-adrenoceptors and phospholipase C in BC3H1 cells. 4. The Ki37 degrees s of all agonists tested were in the same range (0.1 to 1 mM) and showed no simple correlation with their EC50 values. 5. The Ki2 degrees values for all the agonist correlated linearly with their EC50 values but were about 20-100 times lower than the respective EC50 values (except for the partial agonist methoxamine). In order to explain this difference, we propose that the apparent high affinity in the cold could be due to an [3H]-prazosin-induced alteration of the active site of the alpha 1 adrenoceptor, increasing its apparent affinity for catecholamines. PMID- 2905910 TI - Beta-adrenoceptor stimulation inhibits histamine-stimulated inositol phospholipid hydrolysis in bovine tracheal smooth muscle. AB - 1. Histamine and carbachol produced concentration-related increases in the accumulation of 3H-inositol phosphates in slices of bovine tracheal smooth muscle. 2. Noradrenaline alone produced a small stimulation of 3H-inositol phosphate accumulation which was inhibited by the alpha-adrenoceptor antagonist phentolamine. In contrast, when noradrenaline (0.1 mM) was added simultaneously with histamine it significantly reduced the inositol phosphate response to high (greater than or equal to 0.1 mM) concentrations of histamine. However, noradrenaline had no inhibitory effect on the carbachol-induced inositol phosphate response. 3. The non-selective beta-agonist isoprenaline (IC50 = 0.08 microM) and the beta 2-selective agonist salbutamol (IC50 = 0.29 microM) both produced a dose-related inhibition of the inositol phosphate response to 0.1 mM histamine. The inhibitory effect of salbutamol was antagonized by propranolol (KA = 2.4 x 10(9) M-1) and the beta 2-selective adrenoceptor antagonist ICI 118551 (KA = 1.7 x 10(9) M-1). 4. The accumulation of 3H-inositol phosphates induced by histamine increased steadily over a 40 min period after an initial lag period of 3-4 min. Following the simultaneous addition of histamine and salbutamol there was a further delay of 3-4 min before the appearance of the inhibitory effect of salbutamol. 5. The effect of histamine on inositol phosphate accumulation was accompanied by a stimulation of [3H]-inositol incorporation into membrane phospholipids which was reduced by the presence of salbutamol. However, when histamine was used to stimulate maximally [3H]-inositol incorporation during the prelabelling period, salbutamol produced a marked inhibition of histamine stimulated 3H-inositol phosphate accumulation under conditions in which there was no change in the level of incorporation. PMID- 2905911 TI - Interactions between angiotensin II and alpha-adrenoceptor agonists mediating pressor responses in the pithed rat. AB - 1. The aim of the study was to investigate the interactions between angiotensin II (AII) and adrenoceptor-mediated pressor responses in the pithed rat. Emphasis was placed on the effects of AII on blood pressure per se and the possibility of differential effects on alpha 1- and alpha 2-adrenoceptor-mediated pressor responses. 2. A low concentration of the angiotensin converting enzyme (ACE) inhibitor, teprotide (1 mg kg-1) lowered the resting diastolic blood pressure (BP) and attenuated only the second phase components of pressor responses to both alpha 1- and alpha 2-adrenoceptor agonists. Infusion of AII (50 ng kg-1 min-1) did not reverse the attenuating effect of teprotide and did not reliably restore the basal diastolic BP. 3. Although teprotide (10 mg kg-1) did not produce a greater fall in diastolic BP than did the low dose (1 mg kg-1), it attenuated the peak and second phase pressor responses to alpha 1- and alpha 2-adrenoceptor agonists but had no effect on pressor responses to AII or 5-hydroxytryptamine (5 HT). Infusion of AII reversed the effects of teprotide (10 mg kg-1) provided that rats were pretreated with flurbiprofen (5 mg kg-1), confirming that the depressor effects of the higher dose of teprotide are AII-dependent but that demonstration of this was complicated by products of cyclo-oxygenase. 4. The AII-receptor antagonist, saralasin (4 micrograms kg-1 min-1) attenuated alpha 1- and alpha 2 adrenoceptor-mediated pressor responses in a manner similar to that of teprotide (10 mg kg-1), suggesting that in this pithed rat model the alpha-adrenoceptor mediated responses were selectively facilitated by endogenous AII. 5. Infusion of AII (50 ng kg-1 min-1) over a 60 min period did not produce a pressor response in the absence of other drugs but did facilitate pressor responses to alpha adrenoceptor agonists. This confirms that AII can modulate alpha-adrenoceptor mediated responses independently of basal blood pressure. 6. Overall the results indicate a facilitatory role for endogenous AII on alpha-adrenoceptor-mediated pressor responses. This is discussed in relation to the failure to demonstrate this convincingly under similar conditions on sympathetic nerve-mediated pressor responses. PMID- 2905912 TI - Effects of the myocardial-selective alpha 1-adrenoceptor antagonist UK-52046 and atenolol, alone and in combination, on experimental cardiac arrhythmias in dogs. AB - 1. Adrenaline-induced arrhythmias in anaesthetized dogs respired with halothane were attenuated in 3 groups of 6 dogs by either UK-52046, 3.8 +/- 1.4 micrograms kg-1 (mean +/- s.e.mean), atenolol 14.6 +/- 2.1 micrograms kg-1, or a combination containing equal amounts of the two drugs of 0.36 +/- 0.1 microgram kg-1. The pressor response to adrenaline was reduced (P less than 0.01) by UK-52046 but not by atenolol or the combination of both drugs. 2. In a group of 6 dogs with multiventricular ectopic beats 24 h after coronary artery ligation (CAL), UK 52046, 32 micrograms kg-1, increased the number of sinus beats in each 5 min period from 137 +/- 47 to 662 +/- 99 (P less than 0.01); this was associated with a significant (P less than 0.01) fall in blood pressure. Atenolol in doses of up to 800 micrograms kg-1 had no effect. 3. UK-52046, 3.7 +/- 1.4 micrograms kg-1, prevented adrenaline-induced arrhythmias 3-4 days after CAL in 6/6 conscious dogs; atenolol in doses of up to 100 micrograms kg-1 produced an 84.4 +/- 7.4% reduction in the number of ventricular ectopic beats. A combination containing 3.7 +/- 1.1 micrograms kg-1 of each drug prevented the arrhythmia in 6/6 dogs. The pressor response to adrenaline was attenuated (P less than 0.05) by UK-52046, but resting blood pressure was unaffected by the different treatments. An increase (P less than 0.01) in heart rate was associated with both UK-52046 and the combination. 4. Neither UK-52046 (doses up to 64 micrograms kg-1) nor atenolol (up to 800 micrograms kg-1) had any effect upon ouabain-induced arrhythmias in 2 groups of 6 anaesthetized dogs. 5. In a study of the early (1a/1b) arrhythmias of acute myocardial ischaemia, the total number of ventricular ectopic beats occurring within 30 min of CAL was not reduced by 4 micrograms kg-1 UK-52046 but fell (P less than 0.01 compared with placebo) after 8 micrograms kg-1 [median values with ranges for placebo, 4 micrograms kg-1 and 8 micrograms kg-1 respectively 190 (4-674), 246 (9-1204) and 12 (1-154)]. Both doses of UK-52046 were associated with significant falls in blood pressure. 6. The arrhythmias produced by programmed electrical stimulation were studied in 2 groups of 6 conscious dogs, 7-30 days after CAL. With placebo, 4/6 dogs remained unchanged and 2 died: UK-52046 prevented arrhythmias in 2/6, 2 remained unchanged and 2 died (P = 0.29). Compared with placebo, blood pressure fell with doses greater than 4jg kg- '. 7. These results indicate antiarrhythmic effects of UK 52046 in a number of experimental models and suggest an enhanced role of alpha receptors in the genesis of ischaemia-related arrhythmias. In several of the models used, UK-52046 produced haemodynamic changes in keeping with peripheral alpha-adrenoceptor antagonism. PMID- 2905913 TI - Reversals of the neostigmine-induced tetanic fade and endplate potential run-down with respect to the autoregulation of transmitter release. AB - 1. In order to shed more light on the role of presynaptic cholinoceptors in the modulation of transmitter release, the effects of tubocurarine, choline and hexamethonium on neostigmine-induced tetanic fade and run-down of endplate potentials (e.p.ps) in response to indirect stimulation with trains of pulses were studied in the intact and cut isolated phrenic nerve-diaphragm preparation of the mouse, respectively. 2. Tubocurarine, choline and hexamethonium reduced both the tetanic fade and e.p.p. run-down caused by neostigmine, despite the fact that they themselves also induced these two effects. 3. At a given degree of postsynaptic inhibition, choline and hexamethonium caused less e.p.p. run-down and reversed the neostigmine-induced tetanic fade and e.p.p. run-down better than tubocurarine. Moreover, the e.p.p. run-down caused by choline or hexamethonium, but not that induced by tubocurarine, was reciprocally reversed by neostigmine. 4. Tubocurarine, choline and hexamethonium significantly decreased the endplate depolarization induced by repetitive nerve stimulation in the presence of neostigmine. The remaining depolarization continued to grow during repetitive stimulation in the presence of choline or hexamethonium, but not, however, in the presence of tubocurarine; a finding which suggests that choline and hexamethonium but not tubocurarine may be displaced from the receptor by the accumulated acetylcholine. 5. The mutual reversal by neostigmine and cholinoceptor antagonists of e.p.p. run-down may implicate the presence of a positive (physiological) and a negative (pharmacological) feedback regulation for evoked transmitter release via nicotinic cholinoceptors in the mammalian motor nerve, depending on the concentration of acetylcholine within the synaptic cleft. PMID- 2905915 TI - Meleney's synergistic gangrene. PMID- 2905914 TI - Agonists, antagonists and modulators of excitatory amino acid receptors in the guinea-pig myenteric plexus. AB - 1. The receptors for glutamic acid (L-Glu) present in the guinea-pig myenteric plexus-ileal longitudinal muscle preparation have been studied by measuring the muscle contraction induced by numerous putative endogenous agonists acting at these receptors. Furthermore, the actions of different concentrations of antagonists, glycine, Mg2+ and Ca2+ on the ileal contractions induced by L-Glu have been evaluated. 2. The EC50 values of the most common putative endogenous agonists of these receptors were: L-Glu 1.9 X 10(-5) M; L-aspartate 8 X 10(-5) M; quinolinate 5 X 10(-4) M; L-homocysteate 1.4 X 10(-4) M; the dipeptide aspartyl glutamate 8 X 10(-5) M, while N-acetyl-aspartyl-glutamate was inactive. Among the molecules used to classify excitatory amino acid receptors, N-methyl-D-aspartate (NMDA) was the most potent (EC50 5 X 10(-4) M). Kainic and quisqualic acids were almost completely inactive. 3. The responses to L-Glu were competitively antagonized by 2-amino-5-phosphonovaleric acid. They were, also, prevented by hyoscine (10(-7) M) and by tetrodotoxin (3 X 10(-7) M), suggesting that the L-Glu induced ileal contraction was in some way dependent upon an action on the myenteric cholinergic neurones. Kynurenic acid was a non-competitive antagonist, gamma-D-glutamyl-taurine (10(-4) M) and aminophosphonobutyric acid (10(-4) M) did not modify the L-Glu-induced contractions. 4. Glycine (10(-5) M) significantly potentiated the effects of glutamate especially when the ionic composition of the superfusion medium contained concentrations of Ca2+ in the range of 0.6-1.2 mM. Strychnine 3 X 10(-5) M did not modify the actions of glycine. 5. The data presented here confirm the presence of NMDA receptors in the guinea-pig myenteric plexus, and show that these receptors, similar to those present in primary neuronal cultures may be modulated by glycine. PMID- 2905916 TI - Heterogeneity of [3H]neurotensin bindings: studies with dynorphin, L-156,903 and levocabastine. AB - The binding of [3H]neurotensin (NT) to membranes from rat forebrain was complex, exhibiting 'high' affinity (Kd approximately 0.5 nM) and 'low' affinity (Kd approximately 5.0 nM) binding components. Dynorphin A(1-13) (DYN A(1-13] and L 156,903 (N-oxo-3-(10H-phenothiazine-10-yl)propyl-1- arginyl-1-prolyl-1 phenylalanine) potently inhibited [3H]NT binding to brain with shallow biphasic competition curves. Saturation binding studies conducted in the presence or absence of DYN A(1-13) or L-156,903 indicated that these compounds, like levocabastine, exhibited substantial selectivity for 'low' affinity NT site. Structure-activity studies indicated rigid structural requirements for the NT binding activity of DYN A(1-13) and L-156,903. In contrast to the results using brain tissue, DYN A(1-13), L-156,903 and levocabastine were very weak or inactive to inhibit [3H]NT binding to rat uterus. These studies further characterize the heterogeneity of [3H]NT binding in vitro and demonstrate clear tissue differences in binding within a given species. PMID- 2905918 TI - Cardiovascular and respiratory responses to electrical and chemical stimulation of the hippocampus in anesthetized and awake rats. AB - Electrical (30-60-s trains of 0.25-ms pulses at 25 Hz, currents 10-150 microA) and chemical (microinjections of 0.1-0.5 microliters of a 1.0 M glutamate solution) stimulation of the hippocampal formation in the anesthetized and the awake rat evokes marked decreases in heart rate, blood pressure and slower, deeper, more regular respirations. Artificial ventilation (2 ml/breath; 100 breaths/min) has no effect on the cardiovascular responses, indicating that these effects are not secondary to respiratory changes. Administration of methyl atropine (0.4 mg/kg) eliminates the bradycardia response and attenuates or obliterates the blood pressure response but does not alter the respiratory response. This suggests that the cardiovascular responses are mediated partially by the vagus nerve and partially by sympathetic influences. Ablation of the medial frontal cortex, a visceral motor region which projects directly to the nucleus of the solitary tract and which receives a heavy direct projection from the CA1 and subicular cell fields of the ventral hippocampus, markedly attenuates or eliminates the cardiovascular and respiratory responses to stimulation of the ventral but not the dorsal hippocampus. The possibility that the medial frontal cortex may be a relay by which the hippocampus influences cardiovascular responses, including those observed during stress, is discussed. PMID- 2905917 TI - Pressor responses evoked by microinjections of L-glutamate into the caudal ventrolateral medulla of the rat. AB - The caudal medulla of the rat was mapped for cardiovascular sensitive regions by recording changes in mean arterial pressure (MAP) and heart rate evoked by microinjections of L-glutamate (1 nmol/50 nl). Using this technique to selectively activate cell soma in the brainstem, a new pressor area in the caudal ventrolateral medulla has been identified. Several sites located approximately 1 1.5 mm posterior to the caudal medullary depressor zone were found where L glutamate evoked pressor responses of 10-45 mm Hg. The most responsive area was located just dorsal to the lateral aspect of the lateral reticular nucleus at the level of the pyramidal decussation and the caudalmost pole of the inferior olives. Pressor responses at this site averaged 37 +/- 2 mm Hg. Changes in heart rate were inconsistent and both tachycardia and bradycardia were observed. Increases in arterial pressure elicited from the caudal pressor area (CPA) were abolished by ganglionic blockade. Pressor responses evoked from the CPA were also eliminated after functional inactivation of vasopressor neurons in the rostral ventrolateral medulla (RVM) was produced by microinjections of muscimol. Inhibition of CPA neurons by microinjections of GABA had no effect on MAP while GABA markedly reduced MAP when injected into the RVM. These studies demonstrate that a circumscribed region of the caudal ventrolateral medulla contains a population of 'vasopressor' neurons distinct from those located in the rostral medulla. No evidence was obtained to suggest that neural activity in the CPA contributes to the maintenance of arterial pressure. The precise functional role of the CPA in central cardiovascular regulation remains to be determined. PMID- 2905919 TI - Excitatory amino acid receptors in piriform cortex do not show receptor desensitization. AB - We have investigated the proposed role of transmitter receptor desensitization as an explanation for the excitotoxicity rank order of several excitatory amino acid agonists as compared to kainic acid, using a brain slice of rat piriform cortex. Responses to glutamate, aspartate, quisqualate, n-methyl aspartate and kainate showed no evidence of receptor desensitization when studied with very long and large ionophoretic pulses, repeated ionophoretic pulses or by bath perfusion. At least in rat piriform cortex, the suggestion that kainate receptors do not desensitize while those to glutamate and quisqualate do, does not apply to nor explain the more potent kainate excitotoxicity. PMID- 2905920 TI - Is senile dementia of the Alzheimer type associated with hippocampal plasticity? AB - The density of binding sites for excitatory amino acids in the hippocampus of SDAT (senile dementia of the Alzheimer type) patients has been investigated. This was compared to that found in younger and old non-dement cases. In the SDAT hippocampi there was a significant decrease in the glutamate and kainate binding. This reduction correlated positively with the degree of the severity of neurological and pathological disease. In spite of an extensive denervation of SDAT hippocampi, there was no sign of sprouting of mossy fibers; this observation indicates a loss of plasticity in the hippocampus of SDAT patients. PMID- 2905921 TI - Glutamate cytotoxicity in a neuronal cell line is blocked by membrane depolarization. AB - To understand better the proximate mechanism involved in the excitotoxic response to L-glutamate (Glu), we have exploited the Glu receptor present in the N18-RE 105 neuroblastoma-embryonic retinal hybrid cell line. These cells undergo lysis dependent on extracellular Ca2+ when exposed to Glu. We now report that the depolarizing action of Glu is not responsible for its cytotoxic effects. Furthermore, depolarization of these cells with elevated K+, ouabain or veratridine does not cause cytotoxicity but rather protects against the cytotoxic effects of Glu. Our results may implicate a role for voltage-sensitive Ca2+ channels (VSCCs) in cytotoxicity, and depolarization-induced inactivation of VSCCs (Nature (Lond.), 316 (1985) 440-443) as a protection against Glu receptor agonists. Our findings demonstrate a clear dissociation between depolarization and the neuronal degeneration caused by Glu. PMID- 2905922 TI - Stimulation of NMDA receptors induces proteolysis of spectrin in hippocampus. AB - Stimulation of N-methyl-D-aspartate (NMDA) receptors was found to induce proteolysis of brain spectrin in hippocampal slices. The effect was dependent upon extracellular calcium, blocked by the antagonist 2-amino-5-phosphonovalerate (AP5), and was not reproduced by potassium-induced depolarization. These results are consistent with the hypothesis that the involvement of NMDA receptors in plasticity and excitotoxicity is at least partially mediated by calcium-activated proteolysis of cytoskeletal proteins. PMID- 2905923 TI - Electrophysiological and pharmacological properties of neurons within solid basal forebrain transplants in the rat brain. AB - Electrophysiological and pharmacological properties of neurons within solid basal forebrain transplants were studied in adult rats anesthetized with urethane. No specific topography of the neurons recorded was observed within the graft. The mean spontaneous activity of the grafted neurons (GNs) was relatively low (4.9 impulses/s) but not unlike that of other central neurons in situ. A large proportion of GNs fired with regular discharges, but other modes of discharge were also observed. A few rhythmically bursting GNs were recorded having a discharge pattern very much like that of the rhythmically bursting medial septal neurons. The responses of GNs to glutamate, gamma-aminobutyric acid, acetylcholine, serotonin and norepinephrine was fairly similar to those described in other central structures. PMID- 2905924 TI - Glutamate receptors and phosphoinositide metabolism: stimulation via quisqualate receptors is inhibited by N-methyl-D-aspartate receptor activation. AB - Excitatory amino acid receptors in the neonatal rat hippocampus have opposing actions on phosphoinositide (PI) metabolism. Quisqualic acid (QA), but not the QA receptor agonist AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid), potently stimulates inositol phosphate (IP) formation. Activation of NMDA (N methyl-D-aspartate) receptors inhibits the QA-induced stimulation by 70% by a mechanism which is dependent on extracellular calcium. PMID- 2905925 TI - A novel way of removing quiescent astrocytes in a culture of subcortical neurons grown in a chemically defined medium. AB - A new method has been described for removing a very small number of contaminating astrocytes in neuronal cultures (derived from the septal-diagonal band region of 17-day-old embryonic rat brain) grown in a chemically defined medium. The proportion of these glial fibrillary acidic protein (GFAP)-positive cells was usually less than 1.5% up to 10 days, but thereafter their number increased rapidly reaching 10-15% by 22 days in vitro. A prolonged exposure to normally used concentration of cytosine arabinoside (Ara-C; 10 microM) was toxic to both astroglial and neuronal cells, while a brief treatment (48 h) with a low level (4 microM) of Ara-C failed to eliminate these astrocytes, as judged by glutamine synthetase activity and GFAP-positive cell count. However, these quiescent astroglial cells could be easily eliminated if they were induced to proliferate by epidermal growth factor before exposure to Ara-C. The combined treatment with these agents had no effect on the number of acetylcholinesterase-positive cells, and on the development of cholinergic and GABA-ergic neurons, as measured in terms of choline acetyltransferase and glutamate decarboxylase activity, respectively. PMID- 2905926 TI - Acetyl-CoA carboxylase in rat brain. I. Activities in homogenates and isolated fractions. AB - Acetyl-CoA carboxylase (ACC) catalyzes the rate-limiting and/or first committed step in fatty acid biosynthesis. Because fatty acids must be synthesized as components of the galactolipids and phospholipids in myelin, high specific activities of ACC would be expected in brain during myelination and in the myelinating cells, the oligondendroglia, in particular. Under reaction conditions where ACC was linear with time and protein concentration, we found specific activities of 1.7 and 3.1 nmol/min/mg protein in supernatants from forebrains and brainstems, respectively, of 20-day-old rats. In both regions, ACC declined during development, particularly after the age of 20 days. To separate forebrain into discrete fractions containing cells, membrane vesicles, and other components, without destroying the ACC, it was necessary to modify the published methods by adding citrate to the isolation medium and by omitting trypsin. A fraction which sedimented over 1.2 M sucrose showed the highest specific activities and recoveries of ACC. This fraction was rich in small cells, many of which immunostained with antibodies against galactocerebroside and carbonic anhydrase, both of which are localized in oligodendrocytes and immature glial cells. The cells in this fraction also immunostained with antibodies against ACC. The results are consistent with the hypothesis that ACC is an oligodendrocyte associated enzyme, although it probably is not exclusive to cells of that type. PMID- 2905927 TI - Acetyl-CoA carboxylase in rat brain. II. Immunocytochemical localization. AB - Acetyl-CoA carboxylase (ACC) catalyzes the first and, possibly, the rate-limiting step in fatty acid biosynthesis. Because oligodendrocytes must synthesize large amounts of lipid during myelination, the hypothesis was proposed that ACC might be localized in cells of that type. In sections from the brains of 12-day-old rats, ACC immunostaining was observed in glial cells in white matter and gray matter. These cells resembled carbonic anhydrase-positive oligodendrocytes at mature and immature stages of their development. Cells resembling typical oligodendrocytes were also ACC-positive in white matter from the forebrains and brainstems of 15-17 day-old-rats. In both the gray matter and the white matter of 21-day-old rats there were intensely ACC-positive cells that strongly resembled oligodendrocytes. Oligodendrocytes in the brains of adult rats also were ACC positive. While recognizing that some ACC must be present at lower levels in other types of cells and at all ages, it was concluded that the present findings are consistent with its primary locus as the oligodendrocytes, particularly during myelination. Further, enrichment of ACC and carbonic anhydrase in the same type of cell suggested that carbonic anhydrase might serve in providing a substrate, bicarbonate, to be utilized by ACC. PMID- 2905928 TI - Thy-1 expression in the retinotectal system of the chick. AB - Previous investigations into the occurrence of Thy-1 in the chick retina have not clearly defined when the antigen first appears and have not adequately described its expression during the relatively early phases of retinal ontogeny. We have investigated these issues, using improved immunohistochemical procedures and show that Thy-1 is associated with the retinal ganglion cells from the time they begin to differentiate by extending their axonal projections. In addition, we have found that its expression reflects the growth of the optic fibre layer and the elaboration of the ganglion cell dendritic processes into the inner plexiform layer. For the first time we describe the appearance and the developmental expression of Thy-1 in the chick tectum. We have found that Thy-1 is associated with retinal axons from the time of their arrival at the tectum and that its expression reflects the elaboration of the stratum opticum. Within the tectum proper Thy-1 appears first in 3 distinct layers all of which are plexiform in nature. By the time that tectal histogenesis is essentially complete the antigen is expressed by all the layers of the tectum. The implications of these findings are discussed in terms of the development of the individual tissues and with respect to the elaboration of the retinotectal pathway. PMID- 2905929 TI - Immunohistochemical analysis of the development of somatostatin in the reeler neocortex. AB - The development of somatostatin (SS) neurons and fibers has been examined in the dorsolateral cortex of the mouse mutant reeler. Immunohistochemistry was performed using antisera directed primarily against SS28 or SS28(1-12). In the normal mouse at postnatal day 5 (P5), somatostatin (SS) neurons are concentrated in the ventral half of the cortex, in the developing layers V and VI. In the reeler mutant, SS neurons are scattered throughout the radial extent of the cortex, being concentrated in the dorsal half of the cortex in the polymorphic and large pyramidal cell layers. By P20, when the adult pattern of SS neuron distribution is evident in the normal mouse cortex, the distribution of similar neurons in the reeler appears inverted: immunoreactive neurons are concentrated in the dorsal half of the cortex. Immunoreactive fiber distribution follows a developmental pattern similar to that observed for SS neurons. At P5, SS fibers are most dense in layer I and V-VI of the normal cortex, while in the reeler, fibers are predominant in the polymorphic and large pyramidal cell layers. By P10, many fewer immunoreactive fibers can be detected in either normal or reeler mice than at P5. Nevertheless, while SS fibers in the normal cortex are most dense in layers I and V-VI, the reeler cortex exhibits little laminar heterogeneity in the distribution of these fibers. Thus, the SS fiber distribution appears less organized in the reeler cortex. These results suggest that whatever the nature of the genetic alteration resulting in cortical cellular developmental malposition in the reeler, SS cells and fibers, representing a completely intrinsic neocortical cellular system, behave as do all other cortical elements. PMID- 2905930 TI - Somatostatin immunoreactive structures in the developing rat spinal cord. AB - Somatostatin immunoreactive (SOM-I) perikarya were first observed in the ventral horn at E12, in the presumptive intermediate gray area at E14, and in the alar plate of the rostral spinal cord at E14. In general, after their initial appearance, their density increased and then decreased during development. A moderate density of SOM-I varicosities became obvious in the superficial laminae of the E20 dorsal horn. By E12 a few SOM-I perikarya, interpreted to be dorsal root ganglia, were observed lateral to the spinal cord, and by E13, SOM immunoreactivity was visualized within the central and peripheral processes of dorsal root ganglion axons. In the marginal zone, SOM-I fibers were first demonstrable in the ventral funiculus at E14, and in the lateral funiculus at E15. After their initial appearance, their density increased and then decreased with age, with the exception of the dorsal part of the lateral funiculus where it increased at the early stages of development to an apparently stable level. The early detection of SOM immunoreactivity in specific spinal regions corresponds well with the birth dates of cells in those regions. This indicates that the SOM I cells are capable of synthesizing the substance at least as early as they have entered their final cell division. PMID- 2905931 TI - Continuous amphetamine administration induces tyrosine hydroxylase immunoreactive patches in the adult rat neostriatum. AB - Continuous 3-day administration of d-amphetamine sulfate via a subcutaneous minipump induced the appearance of tyrosine hydroxylase immunoreactive patches in the neostriatum of adult Sprague-Dawley and Long-Evans rats at doses (greater than 20 mg/kg/day) that also produced axonal terminal degeneration as evidenced by Fink-Heimer silver grain deposition. The tyrosine hydroxylase patches coincided with striosomes identified by Leu-enkephalin immunoreactivity on adjacent sections. Sham-operated control, naive control, low dose amphetamine- (less than 15 mg/kg/day) and cocaine- (less than 125 mg/kg/day, IV) treated rats did not show tyrosine hydroxylase neostriatal patches nor axonal degeneration. These results suggest that the diffuse neostriatal dopamine system may be more susceptible to the neurotoxic, degenerative action of continuously administered amphetamine than is the islandic dopamine system. PMID- 2905932 TI - [Influence of isoflurane on the neuromuscular block induced by vecuronium in the child]. PMID- 2905933 TI - Antiulcerogenic and antisecretory effects of a novel diphenylmethane derivative and antiestrogen binding site ligand. AB - N,N-Diethyl-2-[4-(phenylmethyl)-phenoxy]-ethanamine hydrochloride (DPPE) is a para-diphenylmethane derivative that binds selectively and with high affinity to the microsomal antiestrogen binding site (AEBS). Recent studies with DPPE indicate that AEBS is closely related to a lower affinity non-H1, non-H2 histamine site that may be associated with calcium channels; the DPPE-AEBS site is different from that which verapamil binds, however, DPPE, but not verapamil, demonstrates antiproliferative effects in vitro and is antiestrogenic in vivo. We now show that DPPE profoundly inhibits restraint and cold stress and ethanol induced gastric ulcer formation, accelerates ulcer healing, attenuates the stress induced rise in plasma corticosterone level, and significantly reduces basal and H2 agonist (dimaprit)-stimulated and, to a lesser extent, bethanechol-stimulated gastric acid output in conscious rats. A nonulcerogenic but prostaglandin depleting dose of indomethacin completely blocks the inhibitory effects of DPPE on stress ulcer formation. Conversely, verapamil only slightly attenuates dimaprit-stimulated gastric acid secretion and exacerbates ethanol-induced gastric ulcers; its anti-stress ulcer effects are only partially attenuated by indomethacin. These findings support the likelihood that the site of action of DPPE is different from that of verapamil, and that an effect on prostaglandins may, at least in part, contribute to its antiulcer and apparent cytoprotective effects. PMID- 2905934 TI - Evidence for the involvement of the benzodiazepine receptor complex in hepatic encephalopathy. Implications for treatment with benzodiazepine receptor antagonists. PMID- 2905935 TI - Biological markers of suicide risk and adolescent suicide. PMID- 2905936 TI - Optimal therapeutic regimen of famotidine based on plasma concentrations in patients with chronic renal failure. AB - An oral therapeutic regimen of famotidine, a histamine H2-receptor antagonist, was evaluated in patients with chronic renal failure who were receiving dialysis three times a week. Measurements of the half-life, bioavailability, and dialysis elimination rate were performed. The half-life of famotidine after oral administration in patients with renal failure was 22.5 hours as opposed to 2.5 hours in control subjects: after intravenous injection, it was 14.6 hours as compared with 2.2 hours. The bioavailability after oral administration was 49.4% in patients with renal failure and 55.2% in control subjects. The dialysis elimination rate was stable and independent of its plasma level, with an average of 41.9%. The oral administration of famotidine (20 mg) immediately after dialysis (60 mg/week) was found optimal and safe. There were no significant side effects with this regimen. PMID- 2905937 TI - [30 years of benzodiazepines]. PMID- 2905938 TI - [Study on the surveillance of house-rat type epidemic haemorrhagic fever]. PMID- 2905939 TI - [First report of an endemic area of epidemic hemorrhagic fever in boarding prefecture]. PMID- 2905940 TI - Perspectives for the chemotherapy of AIDS. AB - Several steps in the replicative cycle of human immunodeficiency virus (HIV) could be envisaged as targets for anti-AIDS drugs. The anionic compound PMEA [9 (2-phosphonyl-methoxyethyl)adenine], the 2'3'-dideoxynucleoside analogues D4T (2',3-deidehydro-2',3'-dideoxythymidine), AzddUrd 3'-azido-2',3'-dideoxyuridine), FddUrd (3'-fluoro-2',3-dideoxyuridine), AzddDAPR (3'-azido-2',3'-dideoxy-2,6' diaminopurine riboside) and the sulfated polysaccharides dextran sulfate and pentosan polysulfate are among the most promising candidate anit-AIDS drugs which have been recently described. They are targeted at either virus-cell binding (dextran sulfate, pentosan polysulfate) or virus-associated reverse transcriptase (PMEA, D4T, AzddUrd, FddUrd, AzddDAPR). PMID- 2905941 TI - Phenothiazine-induced cholestatic jaundice. AB - Proposed mechanisms, clinical features, prevalence, and treatment of phenothiazine-induced cholestatic jaundice are reviewed, and interactions between phenothiazines and other drugs that could theoretically alter the risk of cholestasis are described. Phenothiazine-induced jaundice is classified as a form of cholestatic hepatocanalicular hepatotoxicity and as an acute liver disease. Occasionally cholestatic jaundice may progress to chronic liver disease. The mechanism of hepatotoxicity is not completely understood but may involve a combination of physiochemical, immune, and direct toxic effects. Based on proposed mechanisms, concomitant use of drugs that alter microsomal hepatic enzyme function or have metabolic pathways that interfere with or overlap with those of the phenothiazines could be expected to potentiate or reduce the risk of cholestasis. The estimated prevalence of jaundice with chlorpromazine is 1-2%. The prevalence of jaundice with other phenothiazines is probably similar. The onset of jaundice usually occurs during the first one to four weeks of therapy. In most cases, discontinuation of the offending drug is the only treatment required. Jaundice usually resolves without sequelae two to eight weeks later. Pruritus can be relieved by topical corticosteroid or analgesic therapies or by oral antihistamines or bile acid sequestrants if topical therapy is ineffective. Whenever possible, reinstitution of neuroleptic therapy should be delayed until the reaction has resolved. Selection of a nonphenothiazine neuroleptic agent may be preferred. Phenothiazine-induced cholestatic jaundice occurs relatively infrequently and is usually self-limited; topical agents and oral antihistamines can alleviate the discomfort associated with the reaction. PMID- 2905942 TI - Marked impairment of the effect of hyperglycaemia on glucose uptake and glucose production in insulin-dependent diabetes. AB - The effect of hyperglycaemia per se on glucose utilization and glucose production was evaluated in 12 patients with insulin-dependent diabetes and in 9 non diabetic control subjects. In diabetic patients normoglycaemia was maintained during the night preceding the study by a variable intravenous insulin infusion. During the study endogenous insulin secretion was suppressed by somatostatin (300 micrograms h-1) and replaced by infusion of insulin (0.2 mU kg-1 min-1). Glucose utilization and hepatic glucose production rates were quantified at two plasma glucose concentrations (6.7 and 16.7 mmol l-1) using the two-step sequential hyperglycaemic clamp technique in combination with 3-3H-glucose tracer infusion. Duration of each step was 120 min. In diabetic patients glucose utilization, at a glucose concentration of 6.7 mmol l-1, was not different from normal (mean +/- SE: 2.9 +/- 0.2 vs 3.6 +/- 0.3 mg kg-1 min-1, 0.05 less than p less than 0.10), but the response to marked hyperglycaemia was significantly reduced (5.4 +/- 0.5 vs 9.4 +/- 1.0 mg kg-1 min-1, p less than 0.01). Hepatic glucose production was also normal at 6.7 mmol l-1 (1.4 +/- 0.1 vs 1.4 +/- 0.1 mg kg-1 min-1, NS), but whereas in control subjects glucose production was suppressed during hyperglycaemia of 16.7 mmol l-1 (0.3 +/- 0.4 mg kg-1 min-1, p less than 0.01), a slight increase was observed in diabetic patients (2.0 +/- 0.2 mg kg-1 min-1, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2905943 TI - Biogenic amines and active peptides in the skin of fifty-two African amphibian species other than bufonids. AB - 1. Extracts prepared from dried or fresh skins of 52 African amphibian species, other than bufonids, were subjected to chemical (colour reactions) and biological screening, to determine occurrence and contents of aromatic biogenic amines and peptides active on smooth muscle preparations and blood pressure. 2. Only indolealkylamines were detectable in the skins. They were represented by 5 hydroxytryptamine, its N-methylated derivatives and tryptamine. The indolealkylamines considered included the alkaloid trypargine, a carboline derivative resulting from the condensation of tryptamine with arginine. 3. The peptide families identified in skin extracts of the African frogs were as follows: caeruleins (caerulein, [Asn2, Leu5] caerulein), tachykinins (kassinin, [Glu2, Pro5] kassinin, hylambatin), bradykinins [( Hyp3] bradykinin), xenopsin, thyrotropin releasing hormone, peptide PYLa and the magainins I and II. The last five peptides have been so far identified only in the skin of Xenopus laevis, together with their precursors. 4. Since numerous other peptide molecules await isolation, elucidation of structure, and definition of possible biological activities, the array of peptides occurring in the skin of African amphibians, as in that of Australian and American amphibians, is destined to increase. PMID- 2905944 TI - Non-desensitizing in vitro anaphylactic reaction of chicken visceral muscle. AB - 1. The contractions elicited in pieces of small intestine of actively immunized young chickens upon exposure to the specific antigen (Ag), or Schultz-Dale reaction, have been compared to similar responses of sensitized guinea-pig intestine. 2. Guinea-pig intestine responds, typically, with a large contraction to the first application of Ag. This is followed by a spontaneous relaxation of the preparation, while still in the presence of the Ag, and a rapid desensitization; i.e. further exposures to Ag fail to evoke new contractions. 3. In marked contrast, chicken intestine responds to the Ag with a contraction that remains at its maximal initial value for ca 5 min and then declines only slowly. 4. Exposure to the Ag does not desensitize chicken intestine, which relaxes upon washing out the antigenic protein but contracts again when this is re-introduced in the bath. 5. In addition, consecutive Schultz-Dale reactions of chicken intestine showed a consistent potentiation. They reached a maximal amplitude when the tissue was exposed to the Ag 5-7 times. Such a potentiation is abolished by storing the preparations for 24 hr at 4 degrees C. 6. These observations are discussed in terms of the known properties of avian antibodies. PMID- 2905945 TI - Comparative properties of channel catfish (Ictalurus punctatus) and blue crab (Callinectes sapidus) acetylcholinesterases. AB - 1. Acetylcholinesterases (AChEs) from channel catfish and blue crabs were examined for substrate preference, KmS, effects of inhibitors, and pH and osmotic activity profiles. 2. Similarities were noted for substrate preference along with pH and osmotic optima. 3. Crab AChE had a lower Km (9 x 10(-5) vs 2 x 10(-4) M) and was more sensitive in terms of KI50S than fish AChE to eserine (2.6 x 10(-7) vs 3 x 10(-7) M), malathion (4.5 x 10(-5) vs 1.6 x 10(-4) M) and parathion (6.9 x 10(-5) vs 7 x 10(-4) M). 4. Fish AChE appeared easier to solubilize using Triton X-100. PMID- 2905946 TI - A comparative study of copper ion induced lysis of vertebrate red blood cells. AB - 1. Erythrocytes from different vertebrate classes were tested for susceptibility towards copper ion-induced lysis under identical copper ion concentration and per cent cell volumes. 2. The susceptibility towards lysis was found to be correlated with the rate of copper ion entry into the erythrocytes. 3. GSH levels decline in red blood cells at a rate proportional to the rate of copper ion entry. 4. Hemolysis does not seem to be causally related to the level of GSH in the erythrocytes. PMID- 2905947 TI - Serotonin (5-hydroxytryptamine) turnover in adult female Ascaris suum tissue. AB - 1. The 5-hydroxytryptamine (5-HT, serotonin) turnover was examined in the tissues of adult female Ascaris suum. The 5-HT turnover was highest in the intestine at 34.7 ng 5-HT produced/mg protein/hr and 13.8 ng 5-HT produced/mg protein/hr in muscle tissue. 2. The levels of 5-HT metabolites namely tryptophan, 5 hydroxytryptophan, 5-hydroxytryptamine, 5-hydroxyindole acetic acid and 5 hydroxytryptophol were measured in muscle and intestinal tissue of adult A. suum. 3. Parachlorophenylalanine inhibited 5-HT production in muscle and intestinal tissue providing in situ evidence for the presence of tryptophan hydroxylase in this tissue. 4. Pargyline increased 5-HT production in muscle and intestinal tissue providing in situ evidence for the presence of monoamine oxidase in this tissue. PMID- 2905948 TI - Modulation of smooth muscle activity by excitatory and inhibitory nerves in the guinea-pig stomach. AB - 1. In smooth muscle of the guinea-pig stomach, intramural nerve stimulation evoked cholinergic excitatory junction potential in the fundus and non-adrenergic non-cholinergic inhibitory junction potential in the antrum, yet cholinergic contractions in both regions. 2. This dissociation between electrical and mechanical responses was mainly due to different sensitivity of the membrane for depolarization to acetylcholine. PMID- 2905949 TI - The reductive metabolism of nifurtimox and benznidazole in Crithidia fasciculata is similar to that in Trypanosoma cruzi. AB - 1. Addition of nifurtimox or benznidazole to the NADH-containing mitochondrial fraction of Crithidia fasciculata led to the appearance of the characteristic ESR spectra corresponding to their nitro anion radicals, suggesting that the nitro anion radical is a necessary intermediate in the reduction of both nitro compounds. 2. Nifurtimox anion radical generation by the mitochondrial fraction was insensitive to rotenone and antimycin A but was enhanced by KCN. 3. The nifurtimox anion radical reacted with oxygen under aerobic conditions leading to an increase in the cyanide-insensitive respiration of the intact cells and in the rate of O2- and H2O2 production by the C. fasciculata mitochondrial fraction. 4. In contrast, generation of O2- and H2O2 was not stimulated with pharmacological concentrations of benznidazole. Furthermore, benznidazole inhibited the cyanide insensitive respiration of the intact cells. PMID- 2905950 TI - Alkaloid neurotoxins-dependent sodium transport in insect synaptic nerve-ending particles. AB - 1. Sodium uptake associated with the activation of voltage-sensitive sodium channels by alkaloid activators, batrachotoxin, veratridine, and aconitine in presynaptic nerve terminals isolated from the central nervous system of cockroach (Periplaneta americana) was investigated. 2. Batrachotoxin (K0.5, 0.2 microM) was full agonist as for most effective activator of Na+ uptake; veratridine (K0.5, 2.5 microM) and aconitine (K0.5, 7.6 microM) produced a maximal stimulation of 22Na+ uptake that were 71% and 43% respectively of that produced by batrachotoxin. 3. Veratridine-dependent 22Na+ uptake was completely inhibited by tetrodotoxin (I0.5, 11 nM), a specific inhibitor of the nerve membrane sodium channels. 4. The present study describes appropriate conditions for measuring neurotoxins--stimulated sodium transport in insect central nervous system synaptosomes. The data show that voltage-sensitive sodium channels as defined by specific activation by the alkaloid neurotoxins are qualitatively distinct in insect synaptosomes than those previously described for vertebrate brain synaptosomes, cultured neuronal cell, nerve membrane vesicles and neuroblastoma cells. PMID- 2905951 TI - Induction of metal binding proteins in striped bass, Morone saxatilis, following cadmium treatment. AB - 1. The time course of induction of cytosolic metal binding proteins (MBP) was observed follow up to three daily intramuscular injections of cadmium chloride (0.2 mg cadmium/injection). 2. Low molecular weight binding proteins were resolved by gel permeation chromatography on Sephadex G-75. Based on total metal binding capacity, the concentration of crude MBP increased 2.6 fold. This level of induction of MBP was confirmed by polarographic analysis. 3. Initial binding of cadmium to MBP resulted in displacement of zinc, while at later times, zinc associated with MBP increased above control levels. 4. Using 35S-cysteine incorporation, it was shown that the rate of hepatic MBP synthesis was significantly greater than controls and sham injected fish 18 hr after the third cadmium injection. 5. Due to interfering proteins of molecular weights similar to the metal binding proteins one dimensional PAGE was not capable of verifying induction. However, the metal binding proteins were resolved using two dimensional gel electrophoresis. PMID- 2905952 TI - Pyrethroids and the striatal dopaminergic system in vivo. AB - 1. Type I (permethrin and allethrin) or type II (cypermethrin and fenvalerate) pyrethroids caused 23-37% increases in the striatal content of the dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC). 2. Toxicity symptoms and increases in DOPAC were associated with higher brain concentrations for type I (2.6-5.8 micrograms/gm) than type II pyrethroids (0.4-0.6 micrograms/gm). 3. No specific difference in the interaction between type I and II pyrethroids and the striatal dopaminergic system were recognized. PMID- 2905953 TI - Derivatives of epinephrine, norepinephrine, octopamine and histamine formed by homogenates of Trichostrongylus colubriformis, a nematode parasite of ruminants. AB - 1. Radiolabeled epinephrine, norepinephrine, octopamine and histamine were introduced into homogenates of mixed sexes of the nematode Trichostrongylus colubriformis and the labeled derivatives formed during incubation were identified by HPLC. Vanillylmandelic acid (VMA), 4-hydroxy-3-methoxyphenyl glycol (HMPG) and metanephrine were formed from epinephrine. 2. VMA, HMPG and normetanephrine were produced from norepinephrine. 3. Octopamine was converted into norepinephrine, synephrine and epinephrine. 4. Imidazole-4-acetic acid, 1,4 methylimidazole acetic acid and acetylhistamine were formed from histamine. 5. Inhibitors of monoamine oxidase, catechol-O-methyltransferase and phenylethanolamine-N-methyltransferase were tested for their effects on the formation of certain of these derivatives, and the results suggested that these enzymes were active in the homogenate. PMID- 2905954 TI - The regulation of the corticomelanotropic cell activity in aves. III--Effect of various peptides on the release of MSH from dispersed, perfused duck pituitary cells. Cosecretion of ACTH with MSH. AB - 1. The melanotropin-releasing activity of arginine-vasopressin (AVP), arginine vasotocin (AVT), oxitocin (OT), mesotocin (MT) and corticotropin-releasing factor (CRF) was studied in the duck using dispersed, perfused pituitary cells and a specific alpha-MSH RIA. 2. Log dose-response curves were obtained for all the peptides ranging from 5 to 100 ng/ml. All peptides behaved as partial agonists compared to duck median eminence extracts (DME). 3. AVT and MT displayed an alpha MSH releasing capacity of 60% relative to DME whereas all other peptides behaved as weak agonists with less than 15% capacity relative to DME. 4. AVT and CRF when perfused together acted synergistically on alpha-MSH release yielding a dose response line whose slope approximated that of DME. 5. ACTH was cosecreted together with alpha-MSH in all situations studied with an ACTH to alpha-MSH molar ratio of about 10. 6. It is concluded that CRF and neurohypophyseal peptides may be physiological stimulators of both alpha-MSH and ACTH release in aves. PMID- 2905955 TI - The nuclear binding of dexamethasone-receptor complex from fast and slow skeletal muscle in rats. AB - 1. The binding to isolated muscle nuclei of the complex of dexamethasone with cytosol receptors from rat soleus (Sol) and extensor digitorum longus (EDL) muscles was measured. 2. The ratio of bound to total amount of complex was higher in Sol. 3. The binding of complex per mg of cytosol protein was also higher in Sol. 4. These results suggest that activation and nuclear binding of the steroid receptor complex are not the sites of the different sensitivity of the two muscle types to glucocorticoid. PMID- 2905956 TI - Plasma binding of 1-butanol, phenol, nitrobenzene and pentachlorophenol in the rainbow trout and rat: a comparative study. AB - 1. The in vitro binding of 1-butanol, phenol, nitrobenzene, and pentachlorophenol in trout plasma and rat plasma was determined. 2. Binding to rainbow trout plasma proteins agreed within 9% of that observed in rat plasma. 3. Percentage bound to rainbow trout (2-99%) or rat (10-99%) plasma proteins increased as the log octanol/water partition coefficient of the chemicals increased within the Log P 1 3 range, and was suggestive of hydrophobic interactions in binding. PMID- 2905957 TI - Comparison of hepatic drug metabolizing enzyme activities in several agricultural species. AB - 1. Several pathways of drug metabolizing enzyme activity were measured in hepatic fractions of cattle, sheep, goats, chickens, turkeys, ducks, rabbits and rats. The pathways examined included the O-demethylation of p-nitrophenol, microsomal ester hydrolysis of procaine and glucuronidation of p-nitrophenol, and the cytosolic acetylation of sulfamethazine and sulfation of 2-naphthol. 2. For most enzymatic pathways measured, goats were more similar to sheep (wether) than to cattle (steers). The exception was UDP-glucuronyltransferase activity, which was significantly higher for the goat than for any other species studied. 3. Within the avian subset, the chicken and turkey were usually the most similar species. 4. The activities of arylsulfotransferase isozymes III and IV were particularly low for the duck compared to the chicken and turkey. 5. N-acetyltransferase activity was very high for rabbits and very low for sheep and goats. PMID- 2905958 TI - Constitutive and Aroclor 1254-induced hepatic glutathione S-transferase, peroxidase and reductase activities in genetically inbred mice. AB - 1. Constitutive and Aroclor 1254-induced hepatic glutathione (GSH) S transferases, GSH peroxidase and GSH reductase activities were determined in 12 strains of 8-10 week-old inbred male mice. 2. The constitutive GSH S-transferase activity varied from 2.5 (SJL/JCR) to 8.9 (C57BL/6N) mumol/min/mg protein and the corresponding values for the Aroclor 1254-treated mice were in the range of 7.1 23.0 mumol/min/mg protein. Aroclor 1254 significantly induced GSH S-transferase activity in all mice, however, significant interstrain differences were found in inducibility. 3. Aroclor 1254-treatment caused a 4.2-fold induction of GSH S transferase in NFS/NCR but only a 1.4-fold increase in AKR/NCR mice. Aroclor 1254 significantly induced GSH reductase in all strains studied while GSH peroxidase activity decreased in these mice. 4. The range of hepatic GSH levels in control and Aroclor 1254-treated mice was relatively narrow for both groups (6.59-11.25 microM/g wet tissue). PMID- 2905959 TI - Induction of hepatic aryl hydrocarbon hydroxylase activity in rainbow trout (Salmo gairdneri) exposed to coal liquids. AB - 1. The hepatotoxic response of rainbow trout (Salmo gairdneri) to a middle distillate (MD) and heavy distillate (HD) coal liquid was determined following administration by injection or in food. Hepatic aryl hydrocarbon hydroxylase (AHH) activity was compared to the known AHH inducer, benzo(a)pyrene. 2. Acute toxicities (LD50) of 1500 and 1410 mg/kg were obtained 120 hr after intraperitoneal injection (i.p.) for MD and HD coal liquids, respectively. Only the HD induced AHH activity when injected at 5% and 10% of the acute LD50. 3. Ingestion of 7 or 70 mg HD/kg body weight for 1 week resulted in AHH induction at 5-7 times that of control values. Levels of hepatic AHH activity in fish treated at 7 mg HD/kg declined to 2.6 times control values 7 days after exposure. Maximum induction was observed for the 70 mg HD/kg group that was provided control food for 1 week following 2 weeks of exposure. 4. The hepatic index (HI) or liver to body weight ratio generally increased along with increased activity in the enzyme response system. PMID- 2905960 TI - Changes induced by caffeine, theophylline and theobromine on calcium uptake, respiration and ATP levels in rat-liver mitochondria. AB - 1. The inhibition of calcium uptake and cellular respiration depend on the concentration of the compounds as shown by the concentration-effect curves. 2. The concentrations at which 50% inhibition of the transport of calcium takes place (caffeine 45 mM, theophylline 12 mM, theobromine, 4 mM) do not coincide exactly with those that produce the same effect on cellular respiration (caffeine 60 mM, theophylline 22 mM, theobromine 8 mM). 3. ATP concentrations under different conditions were also determined; a decrease in their value induced by the drugs was observed. No significant differences were observed, however, between the effect produced by the methyl-xanthines. 4. These findings suggest that these compounds are able to affect in some way the maintenance of energy gradients linked to the effects studied. PMID- 2905961 TI - Effects of energy and/or protein restriction on hepatic microsomal mixed function oxidase in male broiler chicks. AB - 1. Effect of energy and/or protein intake on a mixed function oxidase system (MFO) in hepatic microsomes was studied in male broiler chicks. 2. Contents of cytochrome P-450 and b5 in 72 hr starvation were larger than those in 12 and 36 hr starvations. 3. Reduction of energy and protein intake did not change the MFO, except cytochrome P-450. 4. Reduction of energy intake under the same protein intake increased the cytochrome P-450 content and aminopyrine N-demethylase activity. An increase in protein intake under the same energy intake also increased the cytochrome P-450 content. PMID- 2905962 TI - Ramipril inhibition of rabbit (Oryctolagus cuniculus) small intestinal brush border membrane angiotensin converting enzyme. AB - 1. Rabbit small intestinal brush border membranes possessed prominent angiotensin converting enzyme (ACE) activity. 2. Intestinal ACE was located on the lumen surface, as verified by ACE co-enrichment with brush border membrane marker enzymes. 3. Hydrolysis kinetics of rabbit intestinal ACE were comparable to the lung, utilizing the substrate (N-[3-(2-furyl)acryloyl]-L phenylalanylglycylglycine; the Vmax = 543 +/- 51 mumol/min/g and Km = 0.62 +/- 0.09 mmol/l. 4. Intestinal brush border ACE activity was strongly inhibited by the antihypertensive drug Ramipril, which yielded an IC50 value of 5 nmol/l; the ACE activity remained completely inhibited during 15 days after a single dose of 10 mumol/l Ramipril. PMID- 2905963 TI - Differences between chick and turkey embryos in sensitivity to 3,3',4,4' tetrachloro-biphenyl and in concentration/affinity of the hepatic receptor for 2,3,7,8-tetrachlorodibenzo-p-dioxin. AB - 1. 3,3',4,4'-Tetrachlorobiphenyl (TCB) was 20-100 times more toxic in chick embryos than in turkey embryos when injected into eggs. 2. The ED50-value for induction of AHH activity by TCB in the liver of early chick and turkey embryos was estimated to be 0.6 and 6 micrograms/kg egg, respectively. 3. In both species alpha-naphthoflavone was more effective than metyrapone at inhibiting basal and TCB-induced AHH activities. 4. The TCDD receptor was detected in the liver of 7 day-old chick embryos, while it was not found in 9-day-old turkey embryo liver. PMID- 2905964 TI - Pigment migration in fish erythrophores is controlled by alpha 2-adrenoceptors. AB - 1. The aggregation of erythrosomes within erythrophores of the squirrel fish (Myripristis occidentalis; belonging to the family Holocentridae) was, on pharmacological grounds, shown to be mediated by alpha 2-adrenoceptors. 2. The erythrophores were shown to be controlled by adrenergic nerves activating the alpha 2-adrenoceptors. 3. The erythrophores themselves were found to possess a K+ sensitive mechanism of aggregation. 4. Some similarities and differences of the alpha 2-adrenoceptor-mediated chromatosome aggregation in melanophores and erythrophores are also discussed. PMID- 2905965 TI - Neuromuscular electrophysiology of the filarial helminth Dipetalonema viteae. AB - 1. A body wall preparation is described which permits intracellular recording from the somatic muscle cells of the small filarial nematode, Dipetalonema viteae. Using this preparation, resting membrane potentials were measured and spontaneous muscle depolarizations described. 2. Stimulatory effects noted upon the addition of acetylcholine, or the cholinergic agonists suggest the hypothesis that acetylcholine is the excitatory neurotransmitter. However, in contrast with vertebrate tissues, the cholinergic antagonists, d-tubocurarine, hexamethonium and pentolinium do not inhibit somatic muscle activity of the worm. 3. GABA inhibited somatic muscle depolarizations, suggesting the possibility that it may serve as an inhibitory neurotransmitter. 4. The anthelmintic drug, levamisole, produced a depolarizing block. Effects of other pharmacological agents are described, discussed and compared with effects on vertebrate muscles. PMID- 2905966 TI - Evidence that levamisole, pyrantel, morantel, amidantel, deacylated amidantel and hycanthone may act on acetylcholine receptors of central neurones of Helix aspersa. AB - 1. Intracellular recordings were made from identified neurones in the suboesophageal ganglionic mass of the snail, Helix aspersa. Neurones were classified as either "H" cells, inhibited by acetylcholine or "D" cells, excited by acetylcholine. 2. The actions of levamisole, morantel, pyrantel, amidantel, deacylated amidantel and hycanthone were investigated on these neurones and compared to that of acetylcholine. 3. Levamisole was 10.85 +/- 0.56 times less active than acetylcholine on "H" cells but more than 100 times less active on "D" cells. On "H" cells levamisole had a secondary gradual depolarizing effect which was irreversible and resulted in the loss of cell activity. 4. Morantel and pyrantel were 1.12 +/- 0.13 and 2.56 +/- 0.26 times respectively less active than acetylcholine on "D" cells and 5.16 +/- 0.6 and 3.53 +/- 0.63 times respectively less active than acetylcholine on "H" cells. 5. Amidantel was more than 100 times less active than acetylcholine on both "D" and "H" cells while its deacylated derivative was 26.0 +/- 1.0 and 76.0 +/- 3.25 times respectively less active than acetylcholine on "D" and "H" cells. 6. Hycanthone possessed weak inhibitory effects on "H" cells but also appeared to reduce the duration of acetylcholine inhibitory responses when applied immediately after the acetylcholine response had reached its maximum. PMID- 2905967 TI - Clearer demonstration of calcium/calmodulin-dependent events in synaptosomes by use of the differential effects of two calmodulin antagonists, N-(aminohexyl)-5 chloro-1-naphthalenesulfonamide and N-(6-aminohexyl)-1-naphthalenesulfonamide. AB - 1. In order to demonstrate more clearly calcium/calmodulin-dependent events, the differential effects of two calmodulin antagonists, W-7 and W-5, on synapsin I phosphorylation and norepinephrine release associated with calcium influx, were investigated using 32Pi in synaptosomes derived from rat cerebral cortex. 2. The calcium ionophore (A23187)-stimulatory effect on synapsin I phosphorylation and norepinephrine release was markedly reduced by W-7 and slightly reduced by W-5; whereas neither the strong nor the weak calmodulin antagonist had an effect on A23187-stimulated synaptosomal uptake of calcium. 3. Preincubation with H-8 reduced both W-5- and W-7-inhibited A23187-stimulated synapsin I phosphorylation by the same amount but did not affect their inhibitory effect nor the ionophore stimulated norepinephrine release, thereby suggesting that W-5 may serve as an appropriate control for non-calmodulin-mediated effect of both calmodulin antagonists. PMID- 2905968 TI - An analysis of the inhibitory responses of dopamine and octopamine on Helix central neurons. AB - 1. Electrophysiological recordings were made from identified neurons in the isolated suboesophageal ganglionic mass of Helix aspersa. Cells were voltage clamped at testing membrane potential. 2. Bath addition of 1 microM dibutyryl cAMP caused a time dependent enhancement of an evoked IPSP and the dopamine (DA) and octopamine (OA) induced outward currents obtained in these neurons. Forskolin, 0.1 microM, which enhances and MDL 12,330A, 0.12 microM, which depresses adenylate cyclase activity also modified these responses. 3. The DA and OA inhibitory responses were both shown to be potassium mediated events. They were preferentially antagonised by low micromolar concentrations of 4 aminopyridine. Two other potassium channel antagonists, tetraethylammonium and apamin had little effect on the DA and OA responses. 4. Cell sensitivity to DA and OA was greatly enhanced in calcium free/2 mM cobalt Ringer. The reversal potential of the DA response was shifted to a more negative value in calcium free Ringer. Sodium free Ringer was also found to alter the responses to DA or OA but those results were not consistent. PMID- 2905969 TI - Further study of effects of synthetic peptides on identifiable giant neurones of an African giant snail (Achatina fulica Ferussac). AB - 1. Effects of the following peptides at 10(-4) M on identifiable giant neurones of Achatina fulica Ferussac were examined: physalaemin, eledoisin, bradykinin, neurokinin A, neurokinin B, neuromedin B, gastrin releasing peptide decapeptide (neuromedin C), gastrin releasing peptide (14-27), cholecystokinin tetrapeptide, cholecystokinin octapeptide, thyrotropin releasing hormone, Arg-vasotocin, gamma melanocyte stimulating hormone. 2. The six neurones tested were as follows: PON (periodically oscillating neurone), TAN (tonically autoactive neurone), RAPN (right anterior pallial neurone), d-RPLN (dorsal-right parietal large neurone), VIN (visceral intermittently firing neurone) and d-VLN (dorsal-visceral large neurone). 3. Of the peptides examined, only Arg-vasotocin at 10(-4) M produced the excitatory effects on PON, VIN and d-VLN. Physalaemin showed slight inhibitory effects on TAN; this substance was sometimes almost ineffective on the neurone. 4. The other peptides examined were completely ineffective on all of the neurones tested. PMID- 2905970 TI - Immunocytochemical localization of regulatory peptides in six species of trematode parasites. AB - 1. Frozen and paraffin sections of six species of trematodes: Schistosoma mansoni, S. mattheei, S. japonicum, Schistosomatium douthitti, Echinostoma paraensei and Fasciola hepatica have been incubated with antisera against leu enkephalin, FMRF-amide, gastrin-17, luteinizing hormone releasing hormone, neurotensin, oxytocin, prolactin, substance P, thyroid stimulating hormone and cholecystokinin, using indirect immunofluorescence and biotin-avidin horseradish peroxidase detection systems. 2. Of the ten antisera tested, six (leu-enkephalin, FMRF-amide, gastrin-17, luteinizing hormone releasing hormone, substance P and cholecystokinin) showed significant immunoreactivity, primarily in the central and peripheral nervous system, and also perhaps in the osmoregulatory system of the three species of Schistosoma. 3. Immunopositive nerve fibers extended from ganglia to gut wall, uterus and vitelline follicles, and especially from subtegumental nerve plexi to sensory receptors on the surface or in dorsal nippled tubercles. PMID- 2905971 TI - Determination of beta-phenylethylamine in catfish (Parasilurus asotus) tissues by gas chromatography/mass spectrometry. AB - 1. beta-Phenylethylamine (PEA) was detected and quantitated in tissues of the catfish, Parasilurus asotus, by very specific and sensitive gas chromatography/mass spectrometry. 2. The selected ion monitoring was made with a strong quasi-molecular ion of the pentafluoropropionic derivative of PEA in the positive chemical ionization mode. 3. PEA was found in all tissues tested ranging from 2.8 to 38.2 ng/g wet wt tissue. It was highest in the spinal cord, followed by the skin, brain and intestine. PMID- 2905972 TI - Organofluorophosphate-hydrolyzing activity in an estuarine clam, Rangia cuneata. AB - 1. The bivalve Rangia cuneata can enzymatically detoxify the organophosphorus acetylcholinesterase inhibitors DFP and soman. 2. Digestive gland homogenates contained Mazur-type DFPases based on response to Mn2+ ions, and relative rates of DFP: soman hydrolysis. Squid-type DFPase contributed little to the total organophosphate acid (OPA) anhydrase activity of these preparations. 3. The natural substrate(s) and physiological role(s) of OPA anhydrase in R. cuneata has yet to be determined; however, DFPase specific activity was pronounced in the digestive gland, the primary organ involved in bioconcentration and biotransformation of xenobiotics, and in the gills, which are in continuous contact with water-borne chemicals. PMID- 2905973 TI - The effects of adrenergic agonists and age on lipogenesis in avian hepatocytes. AB - 1. Adrenergic inhibition of lipogenesis was examined in vitro using hepatocytes isolated from chickens 2-9 weeks old. 2. Lipogenesis was inhibited by beta 1, beta 2 and alpha 1 agonists. Greatest inhibition occurred when more than one type of receptor was stimulated. 3. Clonidine (alpha 2-agonist) may have stimulated lipogenesis. 4. Responsiveness to the agonists decreased as the chickens got older. PMID- 2905974 TI - Antagonist like action of synthetic alpha 2-adrenoceptor agonists on contractile response to catecholamines in smooth muscle strips isolated from rainbow trout stomach (Salmo gairdneri). AB - 1. The effects of some synthetic alpha 2-adrenoceptor agonists on the mechanical activity and on contractile responses to catecholamines were examined in smooth muscle strips isolated from rainbow trout stomach. 2. Contractile responses to noradrenaline and adrenaline in the rainbow trout stomach strips were due to alpha 2-adrenoceptor activation. 3. Clonidine, p-aminoclonidine, naphazoline and guanabenz caused no mechanical response but concentration-dependently inhibited the contractile responses to noradrenaline and adrenaline without affecting the responses to acetylcholine, carbachol, 5-hydroxytryptamine and methionine enkephalin. The order of potency was naphazoline greater than p-aminoclonidine greater than clonidine greater than guanabenz. 4. It is suggested that in the smooth muscle preparation of the trout stomach, some synthetic compounds (clonidine, p-aminoclonidine, naphazoline and guanabenz), which act on mammalian preparations as alpha 2-adrenoceptor agonists, show an antinoradrenaline ( adrenaline) effect; those compounds can be classified as alpha 2-adrenoceptor antagonists. PMID- 2905975 TI - Acetylcholinesterase and butyrylcholinesterase in the gut mucosal cells of various mammal species: distribution along the intestine and molecular forms. AB - 1. A cholinesterase activity was shown to be present in the homogenates of the gut mucosal cells from seven mammal species examined. 2. The distribution of the cholinesterase activity in the mucosal cells along the intestine differs from one species to another. This distribution is not correlated with that of the aminopeptidase which is a specific marker of the enterocyte plasma membranes. 3. Except rabbit, all the other species contain a (G4) globular tetrameric form and either a (G1) monomeric form (pig, ox) or a (G2) dimeric form (mouse, rat, sheep). Both (G1) and (G2) forms are found with the (G4) form in the mucosal cells of kitten and cat. The solubility characteristics of these various forms were studied by sucrose gradient centrifugations in the presence and the absence of 1% Triton X-100. 4. The mucosal cells from the studied species essentially possess either acetylcholinesterase (rabbit, kitten, cat) or butyrylcholinesterase (ox, pig, sheep, rat, mouse). These findings indicate that both enzymes probably present identical physiological functions in this cell type. PMID- 2905976 TI - O6-methylguanine-DNA methyltransferase levels in tissues of methionine-cysteine deficient subadult and adult mice. AB - 1. Subadult and adult mice were fed during 6 days a diet containing a complete mixture of amino acids or a mixture low in methionine-cysteine. 2. O6 methylguanine-DNA methyltransferase (MT) is the acceptor protein for methyl groups present in DNA at the O-6 position of a guanine that has been methylated by alkylating carcinogenic agents. 3. Upon methionine-cysteine deficiency O6 methylguanine-DNA methyltransferase levels decreased significantly in liver, but seemed unaffected in kidney, lung, testis and brain. 4. Age associated differences were found in liver, with lower values in the subadult than the adult mice leaving the young animals more vulnerable to exposure to alkylating agents. 5. To ensure an efficient repair of DNA lesions both age groups depended on a complete amino acid mixture in the diet. PMID- 2905977 TI - Toxicity of 2-hydrazinoethanol in turkey poults. AB - 1. Toxicity of 2-hydrazinoethanol was investigated in turkey poults 2-6 weeks posthatch. 2. Significant depression of body wt was evident at concentrations of the drug as low as 10 ppm. 3. Severe anorexia closely paralleled a highly significant decrease in water intake. 4. A significant increase in the ratio of granulocytes to agranulocytes was seen in poults fed the drug at a dose of 50 ppm. 5. Under the conditions of this experiment, none of the tissues sampled exhibited pathologic changes consistent with drug injury. PMID- 2905978 TI - Clenbuterol stimulated increase of plasma free fatty acids in reserpinized pigs. AB - 1. Previous studies indicate the beta-adrenergic agonist, clenbuterol, does not stimulate porcine adipose tissue lipolysis or cAMP concentration in vitro but increases plasma free fatty acid concentrations when infused, implying an indirect mechanism in vivo. 2. One indirect mechanism is the release of endogenous catecholamines to increase adipose tissue lipolysis and raise plasma free fatty acids. 3. In pigs treated with reserpine to deplete endogenous catecholamines, clenbuterol infusion increased plasma free fatty acids concentration suggesting that this increase in vivo did not result from release of endogenous catecholamines. PMID- 2905979 TI - [Transluminal catheter angioplasty of the abdominal aorta in Takayasu's arteritis]. PMID- 2905980 TI - Dipeptidyl peptidases of human lymphocytes. AB - In human lymphocytes three dipeptidyl peptidases were discovered in our laboratory. For a correct demonstration of activities of these enzymes discriminating substrates must be used. Dipeptidyl peptidase IV (DPP IV) is revealed with Gly-Pro-4-methoxy-2-naphthylamide (Gly-Pro-MNA) and Fast Blue B (FBB). It is present in the surface membrane of about 40% lymphocytes of the peripheral blood. Only T-lymphocytes bear the reaction. Reacting lymphocytes belong predominantly to OKT4+ subset. Some OKT8+ lymphocytes also react. With more sensitive substrates (Lys-Pro-MNA, Phe-Pro-MNA and Ala-Pro-MNA) a co reaction of DPP II was demonstrated "in situ" and in zymograms. In haemoblastoses a positive reaction in cells indicates their derivation from the T-lineage of lymphocytes. A negative reaction does not exclude a T-cell malignancy, however. A decreased number of DPP IV positive lymphocytes in the peripheral blood indicates a diminished immunocompetent potential of T-cells, e.g. immunodeficiency in patients with malignant lymphoma, gastric and colocrectal carcinoma, AIDS, etc. DPP II demonstrated with Lys-Ala-MNA occurs in about 60% of lymphocytes belonging to T and B subsets. It is localized in lysosomes. Although Lys-Pro-MNA is a more sensitive substrate a co-reaction of DPP IV must always be considered. Patients with chronic B-lymphocytic leukaemia displaying a high number of DPP II+ cells usually have a worse prognosis. DPP I assessed with Gly-Pro-MNA and nitrosalicylaldehyde occurs in about 20% of T and B lymphocytes. The number of positively reacting cells increases after corticosteroid therapy. The influence of the treatment on the activity can be shown very well in histograms of DPP I activity measured by computer-assisted microfluorometry. PMID- 2905982 TI - [The diagnostics of DNA repeat markers]. PMID- 2905981 TI - Current status of beta-blocking drugs in the treatment of anxiety disorders. AB - beta-Adrenoceptor blocking drugs have been used for the treatment of acute stress reactions, adjustment disorders, generalised anxiety, panic disorder and agoraphobia. In general they are effective in these disorders if somatic or autonomic symptoms are prominent but not extreme in degree. Thus, they are of more value for the relatively mild tremor of the anxious violinist in public performance than in the severe shaking noticed during a panic attack. It is most likely that beta-blockers act primarily by blocking peripheral adrenergic beta receptors; symptoms that are mediated through beta-stimulation, such as tremor and palpitations, are helped most. Improvement is noted within 1 to 2 hours and with relatively low doses (e.g. propranolol 40 mg/day). Some recent studies, however, have suggested that when longer treatment using higher doses (e.g. propranolol 160 mg/day) is given, improvement in other forms of anxiety is noted after several weeks of treatment. beta-blocking drugs are useful adjuncts to existing treatments for anxiety and are likely to enjoy wider use now that benzodiazepines are being avoided due to their dependence risks. PMID- 2905983 TI - [DNA diagnosis of muscular dystrophies]. PMID- 2905984 TI - [Research in HLA-domain genes and its practical significance]. PMID- 2905985 TI - [Male infertility caused by sulfasalazine]. PMID- 2905986 TI - Comparison of the effects of dexamethasone 21-acetate and corticosterone on glucocorticoid cytosol receptor depletion and induction of TAT in rat liver. AB - Rapid fall in the amount of glucocorticoid cytosol receptor in target tissues is considered to be a consequence of the receptor translocation to nuclei. The effect of single injection of synthetic (dexamethasone 21-acetate) and natural (corticosterone) glucocorticoid on the depletion and replenishment of cytoplasmic glucocorticoid receptor in rat liver was compared. The effect of 20 micrograms dexamethasone 21-acetate on the extent and duration of the decrease of 3H dexamethasone binding in cytosol was significantly higher than that of 100 micrograms corticosterone. A direct relationship between the amount of depleted receptor and the kinetics of TAT induction was observed. In conclusion, the depletion and replenishment of cytosol receptor closely correlated with the biological potency of the steroid administered. PMID- 2905987 TI - The role of somatostatin in the regulation of anterior pituitary hormone secretion and the use of its analogs in the treatment of human pituitary tumors. PMID- 2905988 TI - Comparison between epidural fentanyl, sufentanil, carfentanil, lofentanil and alfentanil in the rat: analgesia and other in vivo effects. AB - The effects of epidural fentanyl, sufentanil, carfentanil, lofentanil and alfentanil were compared in the rat. All five opiates produced analgesia with the relative order of potency being lofentanil greater than carfentanil greater than sufentanil greater than fentanyl greater than alfentanil, and the relative order of duration at comparative doses lofentanil greater than sufentanil greater than carfentanil greater than fentanyl greater than alfentanil. Because epidural administered opiates still exert some effects within the brain, specificity ratios (defined as the ratio between the ED50s for a prolongation of the tail withdrawal reaction latency and a blockade of the pinna reflex) were calculated. The relative order of specificity between the five opiates was fentanyl greater than lofentanil greater than sufentanil greater than carfentanil greater than alfentanil. These results are discussed in the context of the search for a safe and sufficiently long-acting lipid soluble epidural analgesic. It is concluded that of these five opiates, sufentanil appears to be the best drug of choice for epidural analgesia. PMID- 2905989 TI - Effects of three beta-blockers with different pharmacodynamic properties on platelet aggregation and platelet and plasma cyclic AMP. AB - The effects of three different types of beta-adrenoceptor blocking agents on platelet aggregation and on platelet and plasma cyclic AMP content have been studied in 14 patients with mild hypertension given each drug in turn for two weeks. The drugs were a non-selective blocking agent with high intrinsic sympathomimetic activity, pindolol, the nonspecific blocking agent propranolol, and the beta 1-selective metoprolol. The threshold values of ADP and adrenaline for irreversible platelet aggregation were significantly higher for pindolol and metoprolol than for propranolol. The cyclic AMP content of platelets was higher during pindolol and metoprolol than during propranolol treatment. Pindolol produced a substantial increase in plasma cyclic AMP relative to the other two drugs. Thus, platelet aggregation and cyclic AMP formation are influenced by beta adrenoceptor blockade in proportion to intrinsic sympathomimetic activity and affinity for different beta-adrenoceptor subtypes. PMID- 2905990 TI - Dose-titration study of alfuzosin, a new alpha 1-adrenoceptor blocker, in essential hypertension. AB - An open, dose-titration study of alfuzosin, a new selective post-synaptic alpha 1 adrenoceptor antagonist with additional direct vasodilator properties has been performed. After a 3-week run-in placebo period, 12 patients with essential hypertension received alfuzosin 5 mg oral b.d., and then the dose was doubled every week, up to a maximum of 20 mg q.i.d. if the supine diastolic blood pressure was greater than 90 mm Hg. The study lasted for 4 weeks. Supine blood pressure (SBP) decreased from 160/102 (Day 0) to 148/89 mm Hg and upright blood pressure (UBP) from 151/102 (Day 0) to 137/84 mm Hg. Alfuzosin did not cause any significant change in supine or upright heart rate. In addition, after the first dose of alfuzosin, supine and upright blood pressure and heart rate (SHR and UHR) were measured every 30 min for 5 h. The fall in blood pressure was significant after 90 min and it lasted up to the 5th hour; the maximum effect was observed after 3 h: SBP decreased from 159/103 (time 0) to 137/84 mm Hg and UBP from 150/102 (time 0) to 123/79 mm Hg. SHR was increased from 72 (time 0) to 81 beats/min at the 5th hour and UHR from 87 to 101 beats/min at the 4th hour. A weak but significant correlation was observed between the hypotensive effect 12 h after drug intake and the plasma concentration of the drug at that time. A 10% decrease in supine diastolic blood pressure was found at a drug plasma concentration higher than 7 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2905991 TI - Do nizatidine and cimetidine interact with ibuprofen? AB - The potential for interaction between ibuprofen and two histamine H2-receptor blocking drugs--nizatidine and cimetidine--was investigated in six healthy male volunteers aged 20 to 25 years. Each subject received placebo, nizatidine 300 mg and cimetidine 800 mg orally at 9.00 p.m. daily for six doses in three randomised treatment periods separated by eight days. On the third day of each treatment period ibuprofen 400 mg was administered at the same time and venous blood samples were taken at intervals throughout the night and subsequently up to 84 h after administration. There was no difference in the area under the plasma concentration-time curve, rate of absorption or half-life of elimination of ibuprofen between the three treatments. The elimination half-life of ibuprofen on placebo was 2.04 h. The elimination half-life of nizatidine on ibuprofen was 1.72 h and that of cimetidine was 3.54 h. The latter is higher than previously reported in normal subjects. It is concluded that neither H2-blocker affects the kinetics of ibuprofen in man. PMID- 2905993 TI - HIV-specific T lymphocyte immunity in mice immunized with a recombinant vaccinia virus. AB - Infection by the human immunodeficiency virus (HIV) induces T cell immunity in humans, chimpanzees and macaques. The protective value of this immune response is not clear. We have consequently developed a murine experimental system to study HIV-specific CD4 and CD8 T lymphocyte immunity in vitro and in vivo. BALB/c, DBA/2 and C3H/He mice were immunized with vaccinia virus (VV) recombinant VV 11.39 which expresses the gp160 glycoprotein of HIV-1. Primary and secondary cytotoxic T lymphocyte response to HIV were detected with histocompatible mouse target cells transfected with the HIV-1 env gene. Killer cells were positive for the Thy-1 and Ly-2 (CD8) T cell markers, and were restricted by class I H-2 histocompatibility antigens. Immunological memory specific for HIV-1 envelope antigens was clearly induced by vaccination with VV-11.39:spleen cells from mice vaccinated 4 weeks or more prior to assay generated CD4 and CD8 T lymphocyte responses following stimulation in vitro with HIV envelope antigens. The intensity of these responses increased with consecutive vaccinations, indicating that HIV-specific precursor T cell pools were progressively amplified. Finally, DBA/2 mice vaccinated with VV-11.39 developed protective immunity against a syngeneic tumor which expresses HIV-1 env antigens, leading to accelerated tumor rejection and increased survival. PMID- 2905992 TI - Effects of dilevalol, an R, R-isomer of labetalol, on blood pressure and renal function in patients with mild-to-moderate essential hypertension. AB - The effects of oral dilevalol (an R, R-isomer of labetalol), a new beta adrenoceptor blocker with beta 2-receptor stimulating and alpha-recepter blocking properties on blood pressure, renal function, plasma renin activity (PRA) and plasma aldosterone have been studied in 15 patients with mild-to-moderate essential hypertension treated with it for 6 weeks. Two patients with apparent treatment failure and one patient who developed muscle pain and cramps, and had an elevated creatine phosphokinase level, were excluded from the study. Dilevalol monotherapy 100 mg once daily for 6 weeks significantly lowered both the systolic and diastolic blood pressure compared to placebo. Total renal vascular resistance was significantly reduced, and RBF and GFR remained unchanged. Dilevalol significantly decreased PRA. The results suggest that prolonged daily treatment with dilevalol preserves renal function and produces a concomitant hypotensive action in patients with mild-to-moderate essential hypertension. The ancillary pharmacological properties of dilevalol rather than PRA suppression may be relevant to its renal effects. PMID- 2905994 TI - Regulatory role of the CD8 antigen in both CD3 and CD2 monoclonal antibody induced nonspecific cytotoxicity of class I- and class II-allospecific cytotoxic T cell clones. AB - We investigated the function of the CD8 moiety in antigen-specific and alternative activation of HLA class I- and HLA class II-allospecific CD8+ cytotoxic T lymphocyte (CTL) clones. Monoclonal antibodies (mAb) directed against the CD8 structure were only found to inhibit antigen-specific cytotoxicity of class I-allospecific CD8+ CTL clones and not of a class II-allospecific CD8+ CTL clone. However, cytotoxicity induced by CD3 mAb (used at suboptimal concentrations) or CD2 mAb in both types of CTL clone was blocked by CD8 mAb. The class II-allospecific CD8+ CTL clone was uniformly more difficult to inhibit than the class I-allospecific CD8+ CTL clones and, moreover, also easier to induce to exert nonspecific cytotoxicity by CD2 mAb and CD3 mAb. The absence of CD8 mAb blocking of antigen-specific cytotoxicity of the class II-specific CD8+ CTL clone is, therefore, assumed to result from too strong a triggering signal to be overcome by the down-regulatory signal of the CD8 antigen. These combined findings suggest a down-regulatory function of CD8 not only in T cell receptor (TcR)/CD3 activation, but also in TcR/CD3-controlled alternative activation routes such as the CD2 activation pathway. PMID- 2905995 TI - Regulatory circuits in autoimmunity: recruitment of counter-regulatory CD8+ T cells by encephalitogenic CD4+ T line cells. AB - In this study, pretreatment of Lewis rats with a syngeneic encephalitogenic T cell line (S1) was found to be able to constantly induce resistance to the subsequent induction of transferred experimental autoimmune encephalomyelitis (tEAE). This treatment was capable of protecting recipient animals for at least 2 4 months. Here we show an enhanced suppressor T(anti-S1) cell activity, which can be readily detected in the lymphoid organs of animals which recovered from S1 induced tEAE, or from rats pretreated with attenuated (irradiated, fixative treated or water-lysed) S1 cells. Anti-S1 cells, which uniformly express the CD8 phenotype, were selectively stimulated to grow and expand into lines by confronting primed lymphoid cells with irradiated S1 cells in culture. The proliferative response of anti-S1 cells was independent of myelin basic protein and antigen-presenting cells, and the responses against unrelated encephalitogenic T cell lines were minimal. It was also found that none of the monoclonal antibodies tested (including CD8 and MHC class I antigen-specific antibodies) was able to block S1/anti-S1 interactions. These cells are functionally suppressive to the proliferation of S1 cells in vitro, are specifically cytolytic directed against the EAE-inducing S1 cells and are able to antagonize encephalitogenic capacity of S1 cells in vivo. In vivo elimination of the CD8+ T subset from Lewis rats, using a combined treatment of thymectomy and OX-8 antibody injection before the initial cell transfer, totally blocked the induction of resistance. Our experiments document that induction of functionally active suppressor T cells is responsible for the induced resistance observed in tEAE. PMID- 2905996 TI - Cross-linking of the T cell antigen receptor interferes with the generation of CD4+8+ thymocytes from their immediate CD4-8+ precursors. AB - The majority of thymocytes are immature cells co-expressing the surface markers CD4 and CD8. About two thirds of these cells also express the T cell antigen receptor (TcR), though at a level distinctly lower than found on mature T cells. The direct precursors of these "double-positive" thymocytes are cycling cortical blast cells of the CD4-8+ phenotype. Using a new monoclonal antibody to a constant determinant of the rat TcR alpha/beta, it is shown here that (a) about 50% of these CD8 "single-positive" committed precursor cells already express the TcR alpha/beta, though at very low levels, (b) during short-term suspension culture in medium supplemented only with fetal calf serum they not only acquire CD4 but also TcR alpha/beta levels characteristic of CD4,8 "double-positive" thymocytes, and (c) cross-linking of the TcR during culture inhibits the acquisition of the CD4 antigen in the majority of these cells. PMID- 2905997 TI - CD4+ lymphocytes are extracted from blood by peripheral lymph nodes at different rates from other T cell subsets and B cells. AB - The circulation of lymphocyte subsets through prescapular lymph nodes in sheep has been quantified using a panel of monoclonal antibodies against sheep lymphocyte surface antigens. Differences in the extraction of lymphocyte subsets from blood by the lymph node were found with CD4+ lymphocytes being extracted at a faster rate (1/2) than CD8+, SBU-T19+, major histocompatibility complex class II+ and B cells (1/4 to 1/5). In order to accommodate existing data on organ specific adhesion molecules, one subset specific and one tissue specific, expressed on vascular endothelium could act jointly to regulate the migration of recirculating lymphocytes. PMID- 2905998 TI - Reversal by interferon-gamma of inhibition of delayed-type hypersensitivity induction by anti-CD4 or anti-interleukin 2 receptor (CD25) monoclonal antibodies. Evidence for the physiological role of the CD4+ TH1+ subset in mice. AB - In mice, induction of delayed-type hypersensitivity (DTH) and of antibody formation to sheep red blood cells (SRBC) was inhibited by the anti-CD4 monoclonal antibody (mAb) GK1.5. However, anti-interleukin 2 mAb AMT-13 inhibited DTH response but not antibody formation. The inhibitory action of the mAb on DTH, but not an antibody formation, was reversed by concomitant injection of recombinant mouse interferon-gamma. These data provide the first in vivo evidence for the postulated physiological role of the CD4+ TH1 lymphocyte subset and indicate that the action of anti-interleukin 2 receptor mAb is restricted to this T helper subset. PMID- 2905999 TI - Dipropylacetate-induced shaking behaviour in the rat: a role of spinal alpha 2 adrenoceptors. AB - The role of spinal adrenoceptors in di-n-propylacetate (DPA)-induced shaking behaviour was studied. The alpha 2-agonist p-aminoclonidine in a dose of 5 micrograms was found to suppress the DPA-induced body shakes when injected intrathecally but not when given intraventricularly. There was an enhancement of DPA-induced body shakes after the intrathecal injection of idazoxan while only a slight decrease was found after the intrathecal injection of prazosin. Intrathecal injection of idazoxan but not of prazosin proved to be effective to reverse the DPA-induced body shakes suppressed by p-aminoclonidine. Although the difference in effectiveness after intrathecal and intravenous injection was less than has been described for opiates there are several arguments that indicate an effect confined to the spinal cord. The present results further evidence the notion that the DPA-induced shaking behaviour shares common mechanisms with some of the morphine abstinence symptoms. The data indicate that spinal alpha 2 adrenoceptors are at least partly involved in the suppressive effect of p aminoclonidine on DPA-induced shaking behaviour. PMID- 2906000 TI - Differences between rats and mice in MDMA (methylenedioxymethylamphetamine) neurotoxicity. AB - In both rats and mice a single large dose of methylenedioxymethylamphetamine (MDMA; 25 mg/kg i.p.) caused a fall 3 h after injection in the content of 5 hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in cortex, a fall in noradrenaline in hippocampus and cerebellum, and a rise in dopamine (DA) but fall in dihydroxyphenylacetic acid (DOPAC) in striatum. These effects were transient, levels being essentially back to normal by 24 h after injection. Repeated large doses (3 x 25 mg/kg in 24 h) of MDMA caused a large long-lasting fall in the content of 5-HT and 5-HIAA in cortex in rats but had only a slight effect in mice. Increasing the dose to 3 x 50 mg/kg in mice produced a large long lasting fall in striatal DA. The analogue MDEA(3,4 methylenedioxyethylamphetamine) caused a similar slight fall in 5-HT but in contrast to MDMA caused a slight rise in DA content in mice. The nature and degree of neurotoxicity with methylenedioxyamphetamines appears to be drug and species-specific. PMID- 2906001 TI - Adrenocortical hormone status affects responses to dopamine receptor agonists. AB - The effects of altered adrenocortical hormone status were investigated on hypothermic and behavioural responses elicited following systemically administered apomorphine or LY171555. Hormonal status was modified by surgical adrenalectomy, followed by subsequent replacement therapy with corticosterone, and by chronic corticosterone treatment of intact rats, followed by its withdrawal. The incidence of stereotyped sniffing produced by both apomorphine and LY171555 was increased in the adrenalectomized group and decreased following replacement therapy and in intact rats treated with chronic corticosterone, compared with sham-operated animals and saline-treated controls, respectively. Withdrawal of chronic corticosterone treatment in intact rats reversed the effects of the chronic treatment on dopamine-mediated responses. Similar changes were observed in hypothermic responses to the two dopamine agonists. Striatal D-1 and D-2 dopamine receptor concentration and affinity were unaffected by adrenal hormone modification suggesting that corticosterone may act at a site distal to the dopamine receptor to bring about the observed changes in dopamine-mediated behavioural responsiveness. PMID- 2906002 TI - The effect of SC-19220, a prostaglandin antagonist, on the micturition reflex in rats. AB - SC-19220 (5-20 mg/kg i.v.), a competitive receptor antagonist of PGE, increased the bladder capacity and reduced the voiding efficiency of micturition (elicited by slow transvesical filling) of urethane-anesthetized rats. The effect of SC 19220 was prevented by indomethacin pretreatment, whereas indomethacin per se mimicked the effects of SC-19220. SC-19220 produced a competitive rightward shift of the dose-response curve for the contractile effect induced by PGE2 on strips of rat detrusor muscle in vitro, whereas the amplitude of nerve-mediated twitches was unaffected. These findings support the hypothesis that endogenous PGE2 is physiologically involved in the regulation of vesicourethral motility in this species by facilitating attainment of the micturition threshold during the collection phase of the cystometrogram. PMID- 2906003 TI - Acute reduction of dopamine levels alters responses of basal ganglia neurons to selective D-1 and D-2 dopamine receptor stimulation. AB - Extracellular single unit recording techniques were used to investigate dopamine agonist-induced changes in the tonic activity of globus pallidus neurons in normal control rats, and in rats in which dopamine levels were acutely reduced by alpha-methyl-para-tyrosine (AMPT) pretreatment. Systemic administration of the nonselective D-1/D-2 agonist apomorphine consistently induced large increases in the firing rates of globus pallidus neurons, as shown previously. The D-1 agonist SKF 38393 frequently induced no change in pallidal cell firing rates with doses up to 20 mg/kg; however, firing rates of 40% of the cells were stimulated by more than 20% of baseline and 14% were partially inhibited after 20 mg/kg SKF 38393. Following AMPT pretreatment, SKF 38393 induced only increases and no changes in activity; no decreases were observed. The D-2 agonist quinpirole typically increased pallidal neuron activity in a dose-dependent manner but was markedly less effective at stimulating pallidal neuron activity than apomorphine. In AMPT treated rats, quinpirole's effects were significantly attenuated. Consistent with previous results, most cells showed large rate increases when SKF 38393 and quinpirole were coadministered to normal rats; these increases were similar in magnitude to those induced by apomorphine. In contrast to the observation that AMPT treatment altered the responses of globus pallidus neurons to individually administered quinpirole and SKF 38393, neither the increases in pallidal cell activity induced by apomorphine nor those induced by coadministration of SKF 38393 and quinpirole were significantly attenuated in AMPT-treated rats. The results support the idea that stimulation of both D-1 and D-2 receptors appears to be required to induce apomorphine-like changes in basal ganglia output. Moreover, the effects of individually administered D-1 and D-2 agonists observed in normal rats appear to depend upon the degree to which the complementary receptor subtype is stimulated by endogenous dopamine. PMID- 2906004 TI - Further characterization of the myocardial alpha-adrenoceptors mediating positive inotropic effects in the rabbit myocardium. AB - [3H]Prazosin bound with high affinity to the membrane fraction derived from the rabbit ventricular myocardium. Oxymetazoline displaced [3H]prazosin from its binding site, did not elicit a positive inotropic effect but antagonized the positive inotropic effect of phenylephrine mediated by alpha-adrenoceptors in the presence of a beta-antagonist. Naphazoline was more potent in displacing [3H]prazosin and behaved as a weak partial agonist. YM-12617 (5-[2-[[2-(2 ethoxyphenoxy)ethyl]amino]propyl]-2- methoxybenzenesulfonamide HCl), a potent selective alpha 1-antagonist, displaced [3H]prazosin and antagonized the alpha mediated positive inotropic effect with equal potency. Thus, a good correlation was found between the potency of alpha-antagonists to displace [3H]prazosin and their ability to antagonize the alpha-mediated positive inotropic effect. On the other hand, there was no significant correlation between the Ki and the pD2 value of the alpha-agonists (norepinephrine, epinephrine, phenylephrine and naphazoline), indicating that there is a non-linear relationship between agonist binding to myocardial alpha 1-adrenoceptors and subsequent functional changes. Myocardial alpha 1-adrenoceptors showed some pharmacological characteristics which appear to be different from those in smooth muscle tissues. PMID- 2906005 TI - Specific and non-specific effects of beta-adrenoceptor agonists on guinea pig alveolar macrophage function. AB - The existence of beta-adrenoceptors on guinea pig alveolar macrophage membranes was determined by means of radioligand binding studies. Saturable binding with [125I]cyanopindolol demonstrated 38 +/- 6 fmol binding sites per 10(6) alveolar macrophages with a Kd of 0.85 +/- 0.15 nM. With timolol, atenolol and ICI 118.551 for competition of [125I]cyanopindolol binding it became clear that guinea pig alveolar macrophages possessed adrenergic binding sites of the beta 2-subtype. The cyclic AMP levels of alveolar macrophages could be increased by selective beta 2-adrenoceptor agonists but not by selective beta 1-adrenoceptor agonists. The influence of non-selective beta- and selective beta 1- and beta 2 adrenoceptor agonists on the phagocytic and metabolic responsiveness of alveolar macrophages was also studied. Addition of beta-adrenoceptor agonists had no effect on the uptake of bacteria by alveolar macrophages. Incubation of alveolar macrophages with increasing amounts of non-selective and selective beta 1 agonists resulted in a dose-dependent decrease in the detection of hydrogen peroxide released by alveolar macrophages. This effect was due to the scavenging properties of these drugs. The selective beta 2-receptor agonists, salbutamol and terbutaline, had no effect on the oxidative metabolism of alveolar macrophages. We conclude that guinea pig alveolar macrophages possess beta 2-adrenoceptors on their cell surface and that these receptors are not involved in the phagocytic activity of alveolar macrophages. PMID- 2906006 TI - Effects of neurotensin-related peptides on the motility of the guinea pig oesophagus. AB - Neurotensin, neuromedin N and xenopsin induced a monophasic and concentration dependent contraction of the intact guinea pig oesophagus but kinetensin was without effect. The responses were completely abolished by tetrodotoxin and atropine but were unaffected by hexamethonium. The maximum response induced by neurotensin was reduced (20-30%) by somatostatin and by dynorphin-(1-13) in a naloxone-reversible manner. Neurotensin did not contract the isolated muscularis mucosae. The effects of neurotensin-related peptides on the motility of the oesophagus are mediated exclusively through the release of acetylcholine. PMID- 2906007 TI - Behavioural and neurochemical effects of medetomidine, a novel veterinary sedative. AB - The effects of the novel veterinary sedative, medetomidine, were studied in rats. In addition to a dose-dependent sedation, which at high doses (greater than 100 micrograms/kg) included loss of the righting reflex and hypothermia, there was a concurrent decrease in the turnover rate of biogenic amines in the brain. Noradrenaline turnover was dose dependently decreased as judged by (i) the decrease in the brain concentration of its metabolite, MHPG-SO4, (ii) a decrease in the ability of alpha-methyl-p-tyrosine methyl ester to deplete brain noradrenaline stores and (iii) a dose-dependent decrease in the level of unconjugated MHPG in the CSF of freely moving rats. Brain dopamine turnover was also inhibited at higher doses as judged by the alpha-methyl-p-tyrosine method and by a decrease in the concentration of HVA in the rat brain 4 h after medetomidine. Serotonin turnover as estimated by the ratio of biogenic amine to its metabolite was also significantly depressed. These changes in brain biogenic amine turnover were inhibited by prior or simultaneous administration of alpha 2 adrenoceptor antagonists, either yohimbine or the more specific, novel alpha 2 antagonist, atipamezole. PMID- 2906008 TI - Phorbol 12,13-dibutyrate potentiates alpha 2-adrenoceptor-mediated contraction in the rat saphenous vein. AB - The responses of the rat saphenous vein to potassium depolarization, noradrenaline and B-HT 920 were potentiated significantly by phorbol 12,13 dibutyrate (PDBu) (10 nM). In contrast, only the contraction induced by potassium depolarization was potentiated by PDBu in the rat tail artery. The responses to noradrenaline and methoxamine were slightly inhibited. These results suggest that PDBu may have a differential effect on the responses of the two subtypes of alpha adrenoceptors-potentiation for the alpha 2-adrenoceptors in the rat saphenous vein and inhibition for the alpha 1-adrenoceptors in the rat tail artery. PMID- 2906009 TI - GABA pretreatment enhances glutamate mediated phosphoinositide hydrolysis in neurons. PMID- 2906010 TI - The influence of dopamine agonists and antagonists on indomethacin lesions in stomach and small intestine in rats. AB - Dopamine agents (saline in control groups) were coadministered with indomethacin by either single or repeated application. The ulcerogenic effect (erosions and/or ulcers) of repeated given indomethacin on gastric mucosa differed clearly from that on intestinal mucosa. The effect on intestinal mucosa was markedly greater than after a single dose. The effects of dopamine agents appeared to be more consistent. Domperidone and haloperidol, given as single or repeated doses, strongly aggravated both the gastric and intestinal lesions. Bromocriptine and amantadine had a protective effect. The adverse effects of both dopamine antagonists (increased after repeated administration) were strongly inhibited by the simultaneous administration of either bromocriptine or amantadine. The involvement of the dopamine system (central or peripheral) in the mechanisms that maintain gastric (probably related to cytoprotection also) and intestinal mucosa integrity is therefore suggested. PMID- 2906011 TI - Effects of antimuscarinic agents, H2-blockers and omeprazole on rat chronic gastric ulcer after long- and short-term administration. AB - Two series of experiments were performed on rat chronic ulcer in order to assess the possible curative and mucosal protective properties of 2 week treatments, or the preventive properties of 4 week treatments with antisecretory agents, acting with different mechanisms of action. At the end of the treatments the gastric secretory and motor responsiveness to a gastrin-like stimulus was simultaneously evaluated. The results support the view that antimuscarinic agents as well as H2 blockers cannot be defined as protective and that after a 4 week treatment they can induce modifications of gastric functions. PMID- 2906012 TI - [Certification of paramedical workers]. PMID- 2906014 TI - Celiprolol--new clinical perspectives beyond cardioselectivity. Proceedings of a symposium. Madrid, Spain, 24 January 1987. PMID- 2906013 TI - [Accounting for and analysis of morbidity with temporary loss of work capacity at feldsher-midwife centers]. PMID- 2906015 TI - Celiprolol--overview of 6 years of clinical trials experience. AB - The results of an extensive pre-clinical and clinical research programme indicate that celiprolol is a safe and effective treatment for both hypertension and angina pectoris. Celiprolol is well absorbed, is largely unmetabolized, and is excreted equally in the urine and bile. As a result of this pharmacokinetic profile celiprolol can be safely administered to the elderly and to patients with renal or hepatic impairment. Haemodynamic studies indicate that celiprolol lowers arterial blood pressure, and decreases both renal vascular resistance and peripheral vascular resistance. Celiprolol does not depress myocardial function, neither does it induce bronchoconstriction in asthmatic patients. Weak alpha 2 adrenoceptor antagonism, combined with beta 2-adrenoceptor agonism are thought to contribute to these properties. The antihypertensive efficacy of celiprolol, 200 mg/day, is comparable to that of propranolol, atenolol and nadolol. Moreover, the actions of celiprolol last for 24 h, and are accompanied by less resting bradycardia than that seen with other beta-blockers. The anti-anginal efficacy of celiprolol is similar to that of atenolol, propranolol and metoprolol. In addition, celiprolol decreases the ventricular rate in patients with atrial tachyarrhythmias. This effect results from its ability to slow atrioventricular conduction. Celiprolol is generally very well tolerated. PMID- 2906016 TI - Lipid profile improvement following celiprolol. AB - Many beta-blockers adversely affect serum lipid levels. We have, therefore, monitored blood pressure and serum lipids in 22 patients (mean age: 42.5 years) with essential hypertension (WHO stages I-II) who were treated with celiprolol for 4 weeks, and in 12 patients (mean age: 39.8 years) with essential hypertension (WHO stages I-II) who received celiprolol for 12 months. Standing blood pressure was significantly reduced after 4 weeks and 12 months of treatment, and there were slight decreases in serum cholesterol. In addition, serum triglyceride levels decreased significantly after 4 weeks, and there was a smaller decrease in the patients treated for 12 months. The pathologically elevated pre-treatment lipid values were, therefore, reduced to levels within the normal range. Analysis by lipid electrophoresis showed an increase in the high density lipoprotein (HDL) fraction and a decrease in both the low density lipoprotein (LDL) fraction and the LDL/HDL ratio. During the long-term study there was also a significant reduction in serum fibrinogen. Our results show that celiprolol does not adversely alter serum lipids, and it may even have a beneficial effect on these variables. PMID- 2906017 TI - Celiprolol and atenolol in angina--effects on left ventricular function. AB - Celiprolol, 400 mg once daily, and atenolol, 100 mg once daily, were compared in a double-blind placebo-controlled crossover study of 16 patients with stable angina. Both drugs reduced angina frequency and delayed the onset of ischaemia during exercise, although only celiprolol prolonged exercise time. Celiprolol produced less suppression of heart rate than atenolol during exercise, and atenolol, but not celiprolol, lowered resting and exercise cardiac output. Thus, the ancillary properties of celiprolol, including partial beta 2-adrenoceptor agonist activity and direct vasodilating activity, have detectable effects on cardiac function that may be beneficial in patients with angina. PMID- 2906018 TI - Long-term reduction of peripheral resistance with celiprolol and effects on left ventricular mass. AB - The antihypertensive efficacy of a new beta-blocker, celiprolol, was compared with that of a well established antihypertensive drug, metoprolol. Systemic and forearm haemodynamic effects were investigated using echocardiography and two dimensional pulsed Doppler flowmetry, respectively. Twenty hypertensive patients completed the double-blind crossover randomized study. Each 6-week active treatment period was both preceded and followed by 2 weeks of placebo treatment such that the total duration of the study was 18 weeks. Despite comparable efficacy in reducing systolic and diastolic blood pressures by approximately 10% of the basal value, the two drugs differed in their systemic and haemodynamic effects. Celiprolol significantly decreased forearm peripheral resistance and total peripheral resistance. Cardiac output remained unchanged and forearm blood flow was increased. Metoprolol reduced cardiac output through a reduction in heart rate, but stroke volume was unaltered. Neither drug significantly modified cardiac performance, as evaluated by left ventricular circumferential fibre shortening and left ventricular ejection fraction. Differences in the systemic and regional haemodynamic effects of the two drugs could account for the different blood pressure response seen in some patients. There was no observable change in left ventricular wall thickness or left ventricular mass. These results confirm previous reports which demonstrate that antihypertensive treatment with beta-blockers does not reduce left ventricular mass in patients with a left ventricle of normal size. It is generally accepted, however, that the ability of beta-blockers to reverse left ventricular hypertrophy is unrelated to the individual pharmacological characteristics of each agent. PMID- 2906019 TI - Comparison of the antihypertensive effects of celiprolol and enalapril. AB - Muscular exercise is the most common stress imposed on the cardiovascular system and, in hypertensive patients, it causes an exaggerated increase in the already elevated blood pressure. The evaluation of any antihypertensive drug must, therefore, include an investigation of its effects on the haemodynamic response to exercise. For this reason the effects of celiprolol and enalapril were studied in hypertensive patients, both at rest and during an exercise stress test performed on a bicycle ergometer. The haemodynamic changes observed were very similar at rest: both drugs consistently reduced blood pressure without impairing either myocardial geometry or function. The only between drug difference found at rest was slight bradycardia with celiprolol, whereas heart rate was unaffected by enalapril. By contrast, there was a marked difference in the effect on the blood pressure increase caused by muscular exercise: 24 h after dosing, celiprolol continued to attenuate the hypertensive response to exercise while enalapril failed to show any significant antihypertensive effect possibly because after this time there was a reduction in angiotensin converting enzyme inhibiting activity. Thus, celiprolol and enalapril are both effective once-a-day antihypertensive agents, but celiprolol provides a longer lasting protection from hypertensive peaks caused by exercise. PMID- 2906020 TI - Pharmacological and therapeutic properties of an ideal beta-blocker. AB - With hindsight it is now possible to define some of the additional pharmacological characteristics which enhance the pharmacodynamic and therapeutic efficacy of a drug whose primary purpose is to antagonize competitively sympathetic stimulation of the heart. The ideal pharmacokinetic profile for a beta-blocker includes ready and unimpeded absorption; a predominantly hydrophilic distribution; a relatively long duration of pharmacological activity and alternative routes of elimination. The ideal pharmacodynamic activity of such a drug involves a number of factors, including the essential element of beta 1 adrenoceptor selectivity. In addition, moderate beta 2-adrenoceptor agonist activity and mild stimulation of myocardial contractibility afford enhanced haemodynamic efficacy. The intrinsic ability to relax vascular and bronchial smooth muscle are also highly desirable ancillary pharmacodynamic properties. From the therapeutic aspect, a drug administered with the primary objective of reducing myocardial ischaemia in patients with a coronary heart disease, or of lowering blood pressure in patients with hypertension, should not only prove effective in clinical practice, but should also be shown to have beneficial haemodynamic properties and a minimum of undesirable pharmacological effects. The unique pharmacological profile of celiprolol appears to allow fulfillment of many of these desirable objectives. PMID- 2906021 TI - Transient insulin resistance following infusion of adrenaline in type 1 (insulin dependent) diabetes mellitus. AB - Insulin resistance was assessed after an intravenous infusion of adrenaline (50 ng.kg-1.min-1) or saline (control study) given between 08.00 and 08.30 hours in nine patients with Type 1 (insulin-dependent) diabetes mellitus. The blood glucose level during a somatostatin (100 micrograms/h)-insulin (0.4 mU.kg-1.min 1)-glucose (4.5 mg.kg-1.min-1)-infusion-test performed between 10.30 and 14.30 hours served as an indicator of the total body insulin resistance. Blood glucose was maintained around 7 mmol/l between 08.00 and 10.30 hours by a constant infusion of regular insulin (0.57 mU.kg-1.min-1) and a variable infusion of a 20% glucose solution. The infusion of adrenaline raised plasma adrenaline to 2.7 +/- 0.3 nmol/l (mean +/- SEM) at the end of the infusion; thereafter it returned to its basal level within 30 min. The plasma levels of free insulin, glucagon, cortisol and growth hormone were similar in the adrenaline and the control studies from 08.00 to 14.30 hours. In comparison with the control study the infusion of adrenaline decreased the need for intravenous glucose significantly over the initial 2 h. Furthermore, during the somatostatin-insulin-glucose infusion test the blood glucose rose significantly (p less than 0.05) over the initial 2 h; thereafter no significant differences between the two studies were seen. It is concluded that a short term infusion of adrenaline, resembling the adrenergic hormone response to hypoglycaemia, induces a diabetogenic effect which subsides within 6 h after omission of the adrenaline infusion. PMID- 2906022 TI - The effects of perfluorodecanoic acid on hepatic stearoyl-coenzyme A desaturase and mixed function oxidase activities in rats. AB - Perfluorodecanoic acid (PFDA) causes a dioxin-like toxic syndrome and alters the hepatic oleate/stearate ratio in rats. The acute toxic effects of a single ip dose (50 mg/kg) of PFDA on hepatic stearoyl-CoA desaturase and mixed function oxidases were studied in male Fischer-344 rats, 14 days after dosing. PFDA causes a marked decrease in food intake in rats, resulting in severe body weight loss with delayed lethality (2-3 weeks after dosing). To distinguish the effects of hypophagia from those caused by PFDA, pair-fed control rats were used in addition to ad libitum-fed controls. Stearoyl-CoA desaturase activity, responsible for the conversion of stearoyl-CoA to oleoyl-CoA, was absent in both PFDA-dosed rats and their pair-fed controls at Day 14. Electron transfer through the desaturase system was significantly reduced in PFDA-treated rats only, and in these rats there was a significant reduction in microsomal cytochrome b5, an important component of this electron transfer system. Pentobarbital sleeping times were significantly prolonged in both the PFDA-dosed and pair-fed rats, as compared with the ad libitum-fed controls. This effect was more pronounced in PFDA-dosed rats. Waking plasma pentobarbital concentration was similar in all treatment groups. Hepatic microsomal cytochrome P-450 content was unaffected. Aminopyrine N demethylase activity was greatly reduced in PFDA-dosed rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2906023 TI - Effect of short-term exposure to hexachlorophene on rat brain cell specific marker enzymes. AB - Seven cell specific marker enzymes in brain and optic nerve and morphological evaluation by light microscopy were used to characterize the neurotoxicity associated with exposure of rats to hexachlorophene (HCP; 40 mg/kg/day, po, for 9 days). In vitro exposure to HCP at concentrations up to 100 microM had no direct inhibitory effect on the marker enzymes, validating their use in evaluating brain function in vivo. Rats exhibited a reduction in body weight gain, weakness, and ataxia of the hind limbs by the ninth day of HCP exposure. At 24 hr following the last day of exposure to HCP, the activities of the three neuron specific enzymes, glutamic acid decarboxylase, tyrosine hydroxylase, and choline acetyltransferase, in rat brain were unchanged from those of the vehicle-treated control group. Of the two astroglial enzyme markers measured, a small but significant increase was observed in the activity of nonneuronal enolase in the cerebellum and glutamine synthetase in the hippocampus of HCP-treated rats. The optic nerve appeared to be the most sensitive tissue in that the activity of both the astroglial marker, nonneuronal enolase, and the myelin marker, 2',3'-cyclic nucleotide phosphohydrolase, was significantly decreased following HCP exposure. This decrease in enzyme activity is consistent with the histological observations demonstrating extensive vacuolization and edema in the optic nerve after exposure to HCP. PMID- 2906024 TI - [Cholestasis in pregnancy and normal serum gammaglutamyl transpeptidase activity]. PMID- 2906026 TI - Molecular and phenotypic variation of the white locus region in Drosophila melanogaster. AB - Restriction site and insertion/deletion polymorphism in a 45-kb region of the white locus on the X chromosome in Drosophila melanogaster was investigated for 64 X chromosome lines with six 6-cutter and ten 4-cutter restriction enzymes. A total of 109 polymorphisms were detected (54 restriction sites and 55 insertions/deletions). Estimated heterozygosity per nucleotide for this region (0.004-0.008) was similar to those of the Adh and 87A heat-shock locus regions located on the autosomes in D. melanogaster. This is contrary to a simple prediction based on the theory of mutation selection-balance of partially recessive deleterious mutants which predicts less variation on X chromosomes. Large linkage disequilibria between pairs of polymorphisms (including insertions and deletions) within the transcriptional unit (especially the 3' end of the 1st intron) were observed. As expected from population genetics theory, linkage disequilibria between these polymorphisms were greater for those pairs that are physically closer on the restriction map. Linkage equilibrium was typically observed when the pairs of sites were separated by 2 kb or more. Although significant between-line variation in eye pigment was observed (P less than 0.05), there is little evidence for strong associations between this phenotype and the polymorphisms at the DNA level. PMID- 2906025 TI - Mapping flagellar genes in Chlamydomonas using restriction fragment length polymorphisms. AB - To correlate cloned nuclear DNA sequences with previously characterized mutations in Chlamydomonas and, to gain insight into the organization of its nuclear genome, we have begun to map molecular markers using restriction fragment length polymorphisms (RFLPs). A Chlamydomonas reinhardtii strain (CC-29) containing phenotypic markers on nine of the 19 linkage groups was crossed to the interfertile species Chlamydomonas smithii. DNA from each member of 22 randomly selected tetrads was analyzed for the segregation of RFLPs associated with cloned genes detected by hybridization with radioactive DNA probes. The current set of markers allows the detection of linkage to new molecular markers over approximately 54% of the existing genetic map. This study focused on mapping cloned flagellar genes and genes whose transcripts accumulate after deflagellation. Twelve different molecular clones have been assigned to seven linkage groups. The alpha-1 tubulin gene maps to linkage group III and is linked to the genomic sequence homologous to pcf6-100, a cDNA clone whose corresponding transcript accumulates after deflagellation. The alpha-2 tubulin gene maps to linkage group IV. The two beta-tubulin genes are linked, with the beta-1 gene being approximately 12 cM more distal from the centromere than the beta-2 gene. A clone corresponding to a 73-kD dynein protein maps to the opposite arm of the same linkage group. The gene corresponding to the cDNA clone pcf6-187, whose mRNA accumulates after deflagellation, maps very close to the tightly linked pf-26 and pf-1 mutations on linkage group V. PMID- 2906027 TI - Sequence and structure of the nucleolin promoter in rodents: characterization of a strikingly conserved CpG island. AB - We report the isolation of the complete genes encoding nucleolin from rat and hamster. The DNA clones were obtained from partial genomic libraries by probing with a genomic DNA fragment containing the leader and promoter regions of the mouse nucleolin gene. We have determined the complete nucleotide sequence of the 5'-terminal region for the three rodent species. The sequenced regions extend over 1 kb downstream and upstream from the cap sites and include a conserved CpG island 1500 nucleotides (nt) long. The 5' end of the CpG island in each species has maintained a long alternating purine-pyrimidine sequence which could adopt a Z-DNA conformation. By sequence comparison, 42 blocks of homology are defined in the 5'-terminal region, of which 36 appear in the CpG island and contain numerous conserved CpG dinucleotides. Two blocks, 110 and 49 nt long, encompassing the cap sites and the region immediately upstream, respectively, present features characteristic of regulated genes: a possible TATA box (ATTA), two pyrimidine rich nucleotide stretches and two inverted juxtaposed CCAAT-like boxes (GGTTGG). Furthermore, the adjacent upstream conserved region presents features characteristic of housekeeping genes: four G/C boxes, embedded in a high G + C content sequence, among them one presenting a perfect consensus Sp 1-binding site (GCCCCGCCCC). Among unusual features, we report numerous large G + C-rich conserved sequences located in the first intron. One of these sequences contains two G/C boxes which border a sequence presenting a dyad symmetry (GCGCACGTGCTC). Our findings shed some light on the putative role of the CpG island. We show that CpG-rich sequence motifs are under strong selective pressure over the whole 5' terminal region and are presumably involved in regulatory mechanisms. PMID- 2906029 TI - [The potential co-cataractogenic effects of beta blockers in cataract models in the rat]. PMID- 2906028 TI - [Effect of an H+, K+-ATPase inhibitor, omeprazole (OPZ), on gastric acid secretion and gastric or duodenal lesion. Comparison with an H2-receptor antagonist, famotidine (FMD)]. AB - In pylorus ligated rats, OPZ inhibited gastric acid secretion dose-dependently, with a potency greater than that of FMD. At the same time, OPZ increased gastric K+ secretion and inhibited pepsin and Na+ secretions at the highest dose. In Heidenhain pouch dogs, single injection of OPZ inhibited gastric acid secretion induced by histamine to a degree almost equal to that by FMD. In the case of repeated administration, anti-secretory activity of OPZ was enhanced by up to several days and then remained constant. After several days, the inhibitory activity of OPZ was more potent and longer than that of FMD, and it still had not ceased 22hr after administration. In pylorus ligated rats, OPZ prevented gastric ulceration, and the potency was greater than that of FMD. OPZ promoted healing of gastric and duodenal ulcers induced by acetic acid in rats. At the same doses, FMD failed to promote the healing of both ulcers. In water-immersion stressed rats, OPZ prevented formation of gastric erosions, with a potency greater than that of FMD. In addition, OPZ prevented formation of gastric erosions induced by ethanol in rats. These results indicate that the anti-secretory and anti-ulcer activities of OPZ are superior to those of FMD, so that OPZ should have excellent therapeutic application for peptic ulcers. PMID- 2906030 TI - [With rye pollen micturition is assured. Urologic workshop-discussion "Pollen and the Prostate". 5-7 February 1988, Vendig]. PMID- 2906031 TI - [New aspects of beta-blocker therapy. Pharmacologic data and therapeutic relevance. Satellite symposium of the European Cardiology Congress. 3 September 1988, Budapest]. PMID- 2906032 TI - [Anticholinergic agents in respiratory tract diseases. Therapeutic chances are underestimated. Therapy forum. 28-30 October 1988, Wiesbaden]. PMID- 2906033 TI - Beta-blocking actions of betaxolol on the isolated rat portal vein. AB - The characteristics of the beta-adrenoceptor population mediating the actions of noradrenaline and isoproterenol in the rat portal vein were examined in comparison with those in the rat atria. In the portal vein, the pA2 values obtained for the selective beta 1-adrenoceptor antagonist betaxolol were 100-fold lower than those obtained in the atria, suggesting that in the rat portal vein a population of beta 2-adrenoceptors is highly predominant. PMID- 2906034 TI - Neurotransmitters and intraocular pressure. AB - The role of the ocular autonomic nervous system in IOP regulation has been well established. Pharmacological and autohistoradiographic studies confirmed the high density of beta 2 and alpha 2 receptors on ciliary processes and iris epithelium. Their respective pharmacological activation or blockade is discussed. The role of other ocular neurotransmitters is also complex, as shown by the paradoxical similar action of dopamine agonists and antagonists on IOP. Concerning the cholinergic system, ocular muscarinic receptors are pharmacologically not well documented. Numerous other neurotransmitters may modulate IOP without necessarily leading to the development of new drugs. Drugs of the future will probably concentrate on dopaminergic agonists, cAMP-stimulators such as forskolin, prostaglandins, and cannabinoids. PMID- 2906035 TI - Dopaminergic control of aldosterone secretion. State-of-the-art review. PMID- 2906036 TI - Effect of a somatostatin analog (SMS 201-995) in perfusion on basal and pentagastrin-stimulated calcitonin levels in medullary thyroid carcinoma. PMID- 2906037 TI - Activation of ras oncogenes by chemical carcinogens. PMID- 2906038 TI - Simultaneous analysis of multiple polymorphic loci using amplified sequence polymorphisms (ASPs). AB - In this paper we present a systematic approach to gene mapping and genotyping based on the simultaneous analysis of multiple amplified sequence polymorphisms (ASPs). These genetic markers measure variation in DNA sequences which have been amplified by a polymerase and/or a ligase. The amplified sequence lengths are determined by appropriate choice of oligonucleotides used in the amplification reaction. We describe three classes of ASPs: restriction site polymorphisms, sequence length polymorphisms, and DNA base pair changes not associated with restriction sites. Simultaneous analysis of multiple ASPs using a modified automated DNA sequencing apparatus should be possible because amplification with oligonucleotides provides control over the fragment lengths generated. Development of an automated ASP technology is therefore the next logical step for efficient gene mapping and genotyping of individuals. With this technology, one gel would be sufficient to indicate the most probable locations of a gene and a second gel would permit the selection of the correct location while simultaneously providing a fine structure map. PMID- 2906039 TI - Tyrosine hydroxylase maps to the short arm of chromosome 11 proximal to the insulin and HRAS1 loci. AB - Tyrosine hydroxylase (TH) is the rate-limiting enzyme for catecholamine biosynthesis and a candidate gene for manic-depressive illness. The TH locus was typed for a BglII RFLP using a cDNA clone Ty7 in four large kindreds. Pairwise analyses and multipoint analyses were carried out to map the TH locus more precisely in the region of the linked markers: D11S12, INS, and HRAS1 on 11p. Results confirm the close linkage between TH with these previously mapped markers and support a most likely ordering which places TH on the side of INS where the centromere lies. PMID- 2906040 TI - A primary genetic map of the pericentromeric region of the human X chromosome. AB - We report a genetic linkage map of the pericentromeric region of the human X chromosome, extending from Xp11 to Xq13. Genetic analysis with five polymorphic markers, including centromeric alpha satellite DNA, spanned a distance of approximately 38 cM. Significant lod scores were obtained with linkage analysis in 26 families from the Centre d'Etude du Polymorphisme Humain, establishing estimates of genetic distances between these markers and across the centromere. Physical mapping experiments, using a panel of somatic cell hybrids segregating portions of the X chromosome due to translocations or deletions, are in agreement with the multilocus linkage analysis and indicate the order Xp11 . . . DXS7(L1.28)-TIMP- DXZ1(alpha satellite, cen)- DXS159(cpX73)-PGK1 . . . Xq13. The frequency of recombination in the two approximately 20-cM intervals flanking alpha satellite on either chromosome arm was roughly proportional to the estimated physical distance between markers; no evidence for a reduced crossover frequency was found in the intervals adjacent to the centromere. However, significant interfamilial variations in recombination rates were noted in this region. This primary map should be useful both as a foundation for a higher resolution centromere-based linkage map of the X chromosome and in the localization of genes to the pericentromeric region. PMID- 2906041 TI - A long-range restriction map encompassing the cystic fibrosis locus and its closely linked genetic markers. AB - The cystic fibrosis (CF) locus has been localized to the long arm of chromosome 7 by linkage analysis, and the genetic relationship between CF and the probes J3.11, met, and 7C22 has been extensively studied. To extend this genetic analysis to higher resolution, to provide information on physical distances underlying the genetic relationships, and to set limits to the position of the cystic fibrosis mutation, we have constructed a partial restriction map covering approximately 5 Mb that defines the physical relationship between these and the more recently isolated markers CS.7, XV-2c, Lcn2, and C2/5. Allelic association indicates that CS.7 and XV-2c are close to the CF locus, and an expressed sequence from this region has been described as a candidate gene for this mutation (X. Estivill et al., 1987, Nature (London) 326: 840-845). Using pulsed field gel electrophoresis we have determined the physical order of these markers to be cen-7C22-Lcn2-met-C2/5-XV-2c-CS.7-J3.11-tel and have localized the CF mutation to an interval of less than 1500 kb. A (not unexpected) disproportionality was observed between the currently best estimates of genetic and physical distances, with the interval J3.11-met showing an approximately fourfold higher frequency of recombination than the met-7C22 interval. PMID- 2906042 TI - Genetic mapping of the Wiskott-Aldrich syndrome with two highly-linked polymorphic DNA markers. AB - The Wiskott-Aldrich syndrome (WAS) is an X-linked recessive genetic disease in which the molecular defect is unknown. In 15 families with WAS, seven restriction fragment length polymorphic loci from the X chromosome were used to map the disease locus. Of the eight intervals studied, the likelihood of the WAS gene lying between DXS7 (Xp11.3) and DXS14 (Xp11) was at least 128 times higher than that for any other interval. The most likely gene order is DXS84-OTC-DXS7-WAS DXS14-DXS1-PGK-DXYS1. Close genetic linkage to DXS7 and DXS14 permits accurate prenatal diagnosis and carrier detection with greater than 98% confidence in fully informative WAS families. PMID- 2906043 TI - Human monoamine oxidase gene (MAOA): chromosome position (Xp21-p11) and DNA polymorphism. AB - An essentially full-length cDNA clone for the human enzyme monoamine oxidase type A (MAO-A) has been used to determine the chromosomal location of a gene encoding it. This enzyme is important in the degradative metabolism of biogenic amines throughout the body and is located in the outer mitochondrial membrane of many cell types. Southern blot analysis of PstI-digested human DNA revealed multiple fragments that hybridized to this probe. Using rodent-human somatic cell hybrids containing all or part of the human X chromosome, we have mapped these fragments to the region Xp21-p11. A restriction fragment length polymorphism (RFLP) for this MAOA gene was identified and used to evaluate linkage distances between this locus and several other loci on Xp. The MAOA locus lies between DXS14 and OTC, about 29 cM from the former. PMID- 2906044 TI - A primary map of ten DNA markers and two serological markers for human chromosome 19. AB - We have constructed a primary map of 10 DNA and 2 protein markers for chromosome 19. Three of the markers define loci with a variable number of tandem repeats (VNTRs); 3 define genes--insulin receptor, low-density lipoprotein (LDL) receptor, and apolipoprotein CII; and 2 are classical markers for blood group antigens (Lewis and Secretor). The estimated genetic distance covered by the map is 137 cM in males and 189 cM in females. In some regions of the chromosome we found significant differences in recombination frequencies according to sex. This set of markers will be efficient for linkage studies in families segregating genetic defects and will provide anchor points for a high-resolution map of chromosome 19. PMID- 2906045 TI - A linkage group of five DNA markers on human chromosome 10. AB - Five chromosome 10 DNA markers (D10S1, D10S3, D10S4, D10S5, and RBP3) were typed in five large pedigrees with multiple endocrine neoplasia type 2A (MEN-2A) and in five non-MEN-2A pedigrees. Linkage analyses showed that these loci and the locus for MEN-2A (MEN2A) are in one linkage group spanning at least 70 cM. The order of the marker loci is RBP3-D10S5-D10S3-D10S1-D10S4, with interlocus recombination frequencies of 7, 13-19, 19, and 19%, respectively, all on the same side of MEN2A. Analyses of sex-specific recombination frequencies indicated no significant differences between males and females for any of the map intervals studied. Previous localization of D10S5 and RBP3 to the proximal region of the long arm and the pericentric region, respectively, comparison of results with other studies, and our preliminary results with other chromosome 10 markers suggest that the D10S4 end of the map extends into the long arm. Our linkage map has been constructed using only two- and three-locus analyses. It will be possible to combine our results with those of other groups to construct a more detailed and accurate genetic map of chromosome 10. PMID- 2906046 TI - D10S20, a previously unmapped RFLP (OS-3), is located on 10q near D10S4. AB - The locus recognized by the probe OS-3 is assigned to chromosome 10 both by Southern blot analysis of a panel of somatic cell hybrid DNAs and by genetic linkage to markers already assigned to chromosome 10. In Caucasians this probe recognizes a three-allele TaqI RFLP as well as two-allele BanII and RsaI RFLPs which are both in strong linkage disequilibrium with each other and with the TaqI RFLP. The D10S20 locus defined by this probe maps 5.5 cM distal to D10S4 on the long arm of chromosome 10. Because this human clone hybridizes with mouse genomic DNA, it will be useful in comparative mapping studies. PMID- 2906047 TI - The human "interferon-beta 2/hepatocyte stimulating factor/interleukin-6" gene: DNA polymorphism studies and localization to chromosome 7p21. AB - The human interferon-beta 2 gene (IFNB2) product is identical to that for the B cell stimulation factor-2 (BSF-2), the hybridoma growth factor (HGF) ("interleukin-6"), and the hepatocyte stimulating factor (HSF). Proteins derived from this gene mediate the plasma protein response to tissue injury (acute-phase response) and regulate the growth and differentiation of both B and T cells. By using the enzymes MspI, BstNI, and BglI, three polymorphic systems were detected with probes for the IFNB2 gene. The MspI and BglI polymorphisms are likely to be due to base pair substitutions; the BstNI polymorphism was revealed by nine other enzymes and is likely to be due to DNA insertions within 1 kb of the 3' flanking region of the gene. This region is rich in AT dinucleotides, and slippage at DNA replication may generate the insertions of between 0.07 and 0.23 kb that were observed. The polymorphic MspI site also lies within the vicinity of the fifth exon. The BglI polymorphic site is likely to lie in 5' flanking DNA. The three polymorphisms are separate, and a variety of haplotypes was observed. A low level of linkage disequilibrium exists between the MspI and the BglI alleles. MspI and BstNI polymorphisms were observed in Caucasoids, CAR Pygmies, Zaire Pygmies, Melanesians, and Chinese but at differing frequencies, and not all alleles were present in all populations. The BglI polymorphism was observed in Caucasoids and Africans only. Linkage studies involving the IFNB2 gene and 27 other chromosome 7 markers have localized it to between D7S135 and D7S370 at 7p22-p21.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2906048 TI - Regional localization of mouse Abl and Mos proto-oncogenes by in situ hybridization. AB - Two proto-oncogenes, Abl and Mos, have been physically localized on their respective mouse chromosomes by in situ hybridization. By means of Robertsonian translocations to facilitate chromosome identification, Abl was regionally assigned to 2B while Mos was assigned to 4A1-A2. Polymorphisms for these genes have not been reported in genomic DNA from standard inbred strains, nor were they found in this study, thereby prohibiting genetic mapping by meiotic recombination. These physical mapping data, however, extend the number of homologous genes assigned to chromosomal regions in both man and mouse, and better define the segments of conservation on mouse chromosome 2/human chromosome 9 and mouse chromosome 4/human chromosome 8, respectively. PMID- 2906049 TI - Idiotype regulation of thymus autoantibodies. AB - Rabbit antisera specific for idiotypic determinants (Id) of monoclonal Thy-1 autoantibodies were tested for their capacity to elicit Id-bearing thymus autoantibodies in mice. Rabbits were immunized with the 20-10-5 monoclonal IgM Thy-1 autoantibody, and idiotype-specific antibodies (anti-Id) were obtained by affinity chromatography. BALB/c and C3H mice were immunized by repeated i.p. injections of the anti-Id reagent. Control mice received repeated injections of purified normal rabbit immunoglobulin (NRIg) sheep red blood cells (SRBC) or human serum albumin (HSA). The sera of the treated mice were examined for their reactivity with anti-Id xenoantisera and for their capacity to react with thymus cells. The injection of anti-Id sera into either BALB/c or C3H mice resulted in a significant increase in the serum concentration of Id-bearing immunoglobulins, while no such change was observed in the sera of mice injected with NRIg. The administration of anti-Id, NRIg, SRBC or HSA resulted in a gradual increase in the concentration of autoantibodies reactive with thymus cells. Incubation with anti-Id sera prevented the binding to thymus cells of autoantibodies induced by anti-Id treatment. In contrast, the binding capacity of autoantibodies induced by NRIg, SRBC or HSA was unaffected by anti-Id sera. Thus, only the thymus autoantibodies induced by anti-Id treatment expressed Id-determinants. These results demonstrate the existence of a regulatory network in the formation of thymus autoantibodies. PMID- 2906050 TI - Increased efficacy and toxicity of lidocaine in patients on beta-blockers. AB - The greatest differences in ventricular arrhythmias and adverse effects of lidocaine observed in this study were between patients on both lidocaine and a beta-adrenoceptor blocking agent and those on neither drug. Although free fractions of lidocaine and methylglycylxylidine tended to be higher in patients on beta-adrenoceptor blocking agents, this difference was not significant nor were any other differences in serum drug levels observed. PMID- 2906051 TI - HTLV-V: a new human retrovirus associated with cutaneous T-cell lymphoma (mycosis fungoides). PMID- 2906052 TI - Coral ulcer as a vasculitis. PMID- 2906053 TI - Structural requirements for dermorphin opioid receptor binding. AB - Structural features influencing binding activity of dermorphin to opioid receptors have been investigated in the rat brain through the synthesis and evaluation of binding affinity of a series of synthetic dermorphin analogs. Tritiated dermorphin was used as primary ligand. The single population of high affinity dermorphin binding sites present in the rat brain is clearly of an opioid nature since bound radiolabeled dermorphin was fully displaced with high affinity either by morphine or naloxone. Displacement of tritiated dermorphin by all alkaloid opiates or dermorphin related peptides tested was monophasic, consistent with simple competitive inhibition at a single population of binding sites. Dermorphin (Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2) was the most potent competitor in all experiments. The D-configuration of the amino acid residue in position 2 was found to be of crucial importance for binding. Replacement of D Ala2 with L-Ala led to a deleterious effect, this analog being 1/5000th as potent as dermorphin in displacing bound tritiated dermorphin from its receptor. Shorter dermorphin homologs, dermorphin-(1-4)-NH2 and dermorphin-(1-3)-NH2, were found to be 20 and 40-fold less potent, respectively, than dermorphin. The C-terminal carboxamide function is of significant importance for manifestation of the full intrinsic binding potency of dermorphin. Deamidated dermorphin had 1/5th the potency of the parent peptide. This suggests that while the whole dermorphin sequence is required for the expression of the full intrinsic binding activity of the molecule, the N-terminal tripeptide is a key structure as it contains the features which allow receptor recognition. PMID- 2906054 TI - Synthesis of somatostatin analogs resistant to the action of trypsin. AB - The synthesis of a series of octapeptides based on the somatostatin analog cyclo( Asn-Phe-Phe-D-Trp-Lys-Thr-Phe-Gaba-) containing the substitutions [Aap9], [D Lys9], [L-Trp8, D-Lys9], [L-Orn9] and [D-aThr10] is reported. The analogs were designed and have been shown to inhibit proteolysis at the proposed (1) primary cleavage site between Lys9-Thr10 and thereby increase their stability to enzymic attack. PMID- 2906055 TI - Health behaviors and beliefs of four allied health professions regarding health promotion and disease prevention. AB - Certified nurse midwives, certified physician assistants, registered dental hygienists, and registered dietitians were surveyed to determine to what extent important health promotion and disease prevention behaviors are a part of their lifestyle. Also assessed were beliefs about health promotion and disease prevention practices. The study found that the respondents perceive themselves as important providers of health promotion and preventive services. Although most of the respondents are good health role models, many should consider changes in their own behaviors. Additionally, continued learning by many of these professionals appears warranted, particularly in recognizing the significance of certain health behaviors as they relate to preventing disease and promoting health. PMID- 2906056 TI - Purification, characterization and antimicrobial spectrum of a bacteriocin produced by Pediococcus acidilactici. AB - An antimicrobial peptide designated pediocin AcH was isolated from Pediococcus acidilactici strain H. The pediocin AcH was purified by ion exchange chromatography. The molecular weight of pediocin AcH was determined by SDS-PAGE to be about 2700 daltons. Pediocin AcH was sensitive to proteolytic enzymes resistant to heat and organic solvents, and active over a wide range of pH. Pediocin AcH exhibited inhibition against several food spoilage bacteria and foodborne pathogens including Staphylococcus aureus, Clostridium perfringens and Listeria monocytogenes. It was bactericidal to sensitive cells and acted very rapidly. The bactericidal effect was not produced by either cell lysis or apparent loss of membrane permeability. PMID- 2906057 TI - Betablockers in depression with hypertension. PMID- 2906058 TI - The number of functional catalytic sites on F1-ATPases and the effects of quaternary structural asymmetry on their properties. AB - Recent structural and kinetic studies of F1 and F0F1 are reviewed with regard to their implications for the binding change mechanism for ATP synthesis by oxidative phosphorylation and photophosphorylation. It is concluded that at least two and probably all three of the catalytic sites on F1 are functionally equivalent despite permanent structural asymmetry in the soluble enzyme. A rotary mechanism in which all three catalytic subunits experience all possible interactions with the single-copy subunits during turnover is thought not to apply to soluble F1 but remains an attractive model for the membrane bound enzyme. PMID- 2906059 TI - Chemical modification of active sites in relation to the catalytic mechanism of F1. AB - Recent studies of chemically modified F1-ATPases have provided new information that requires a revision of our thinking on their catalytic mechanism. One of the beta subunits in F1-ATPase is distinguishable from the other two both structurally and functionally. The catalytic site and regulatory site of the same beta subunit are probably sufficiently close to each other, and the interaction between the various catalytic and regulatory sites are probably sufficiently strong to raise the uni-site rate of ATP hydrolysis by several orders of magnitude to that of promoted (multi-site) ATP hydrolysis. Although all three beta subunits in F1 possess weak uni-site ATPase activity, only one of them (beta') catalyzes promoted ATP hydrolysis. But all three beta subunits catalyze ATP synthesis driven by the proton flux. Internal rotation of the alpha 3beta 3 or beta 3 moiety relative to the remainder of the F0F1 complex did not occur during oxidative phosphorylation by reconstituted submitochondrial particles. PMID- 2906061 TI - Mechanism of F1-ATPase studied by the genetic approach. AB - E. coli F1-ATPase has been studied mainly by the genetic approach. Mutations in either the alpha or beta subunit modified the kinetics of multisite and uni-site hydrolysis of ATP. The mechanism of F1-ATPase and the essential amino acid residues of beta subunits are discussed. PMID- 2906060 TI - ATP synthases--structure of the F1-moiety and its relationship to function and mechanism. AB - A great deal of progress has been made in understanding both the structure and the mechanism of F1-ATPase. The primary structure is now fully known for at least five species. Sequence comparison between chloroplast, photobacteria, aerobic bacteria, and mitochondrial representatives allow us to infer more general functional relationships and evolutionary trends. Although the F1 moiety is the most studied segment of the H+-ATPase complex, there is not a full understanding of the mechanism and regulation of its hydrolytic activity. The beta subunit is now known to contain one and probably two nucleotide binding domains, one of which is believed to be a catalytic site. Recently, two similar models have been proposed to attempt to describe the "active" part of the beta subunits. These models are mainly an attempt to use the structure of adenylate kinase to represent a more general working model for nucleotide binding phosphotransferases. Labelling experiments seem to indicate that several critical residues outside the region described by the "adenylate kinase" part of this model are also actively involved in the ATPase activity. New models will have to be introduced to include these regions. Finally, it seems that a consensus has been reached with regard to a broad acceptance of the asymmetric structure of the F1-moiety. In addition, recent experimental evidence points toward the presence of nonequivalent subunits to describe the functional activity of the F1-ATPase. A summary diagram of the conformational and binding states of the enzyme including the nonequivalent beta subunit is presented. Additional research is essential to establish the role of the minor subunits--and of the asymmetry they introduce in F1--on the physiological function of the enzyme. PMID- 2906063 TI - Determination of roxatidine in human plasma, urine and milk by capillary gas chromatography using nitrogen-selective detection. AB - An assay is described for the determination of roxatidine in human plasma, urine and milk by gas chromatography. Roxatidine is extracted from the basified matrix with dichloromethane and esterified with propionic anhydride prior to analysis of the extracts by capillary gas chromatography using a nitrogen-specific detector. Detection limits are 5 ng/ml for plasma and milk and 1 microgram/ml for urine, making the assay suitable for obtaining pharmacokinetic data from volunteer trials. PMID- 2906062 TI - Role of energy in oxidative phosphorylation. AB - This article reviews the current status of information regarding the role of energy in the process of oxidative phosphorylation by mitochondria. The available data suggest that in submitochondrial particles (SMP) energy is utilized for the binding of ADP and Pi and for the release of ATP bound at the catalytic sites of F1-ATPase. The process of ATP synthesis on the surface of F1 from F1-bound ADP and Pi appears to be associated with negligible free energy change. The rate of energy production by the respiratory chain modulates the kinetics of ATP synthesis between a low Km (for ADP and Pi)-low Vmax mode and a high Km-high Vmax mode. The Km extremes for ADP are 2-3 microM and 120-150 microM, and Vmax for ATP synthesis at high rates of energy production by bovine-heart SMP is about 440 S-1 (mole F1)-1 at 30 degrees C, which corresponds to 11 mumol ATP (min.mg of protein)-1. The interaction of dicyclohexylcarbodiimide (DCCD) or oligomycin at the proteolipid (subunit c) of the membrane sector (F0) of the ATP synthase complex alters the mode of ATP binding at the catalytic sites of F1, probably to one of lower affinity. It has been suggested that protonic energy might be conveyed to the catalytic sites of F1 in an analogous manner, i.e., via conformation changes in the ATP synthase complex initiated by proton-induced alterations in the structure of the DCCD-binding proteolipid. Finally, the relationship between the steady-state membrane potential (delta psi) and the rates of electron transfer and ATP synthesis has been discussed. It has been shown, in agreement with the delocalized chemiosmotic mechanism, that under appropriate conditions delta psi is exquisitely sensitive to changes in the rates of energy production and consumption. PMID- 2906064 TI - Simultaneous determination of floctafenine and its main metabolites, floctafenic and hydroxyfloctafenic acid, using high-performance liquid chromatography with gradient elution. PMID- 2906065 TI - Preparative high-performance liquid chromatography of peptides on a new reversed phase packing material, Kromasil C18. AB - Preparative reversed-phase high-performance liquid chromatography has found wide use in the production of peptides for pharmaceutical formulations. Purity of the substance and overall economy of the chromatographic system are the most important criterias. In this sense optimized, silica particles and production process with capability to separately control parameters important to chromatography, are essential to high-performance chromatography. Kromasil C18 packing material was tested and evaluated in respect of its selectivity, flow and pressure properties, resolution, load capacity, recovery, adsorption effects, mechanical strength and chemical degradation. PMID- 2906066 TI - Administration of butaperazine and plasma methionine-enkephalin levels in schizophrenic and affective disorder patients with tardive dyskinesia. AB - The levels of plasma methionine-enkephalin in male chronic schizophrenic and affective disorder patients with or without tardive dyskinesia (TD) were in a range similar to those of sex-matched adult control volunteers. Administration of butaperazine resulted in significant changes (increases) of neuropeptide plasma concentration only in the affective disorder with TD subgroup, reaching statistical significance over their own baseline at 8, 10.5, and 24 hours, and at baseline (0 hr), 8-, and 48-hour intervals when compared with the affective disorder patients without TD. PMID- 2906067 TI - Tardive dyskinesia, dopamine receptors, and neuroleptic damage to cell membranes. AB - The long-term treatment of schizophrenic patients with neuroleptics is associated with neuroleptic accumulation in neuromelanin-containing cells with ensuing nigral cell damage. Thus, in addition to early or short-term up-regulation of D2 dopamine receptors, the late stage denervation supersensitivity may result in a further proliferation of D2 dopamine receptors in those parts of the human striatum controlling mouth-lips-tongue motion. Young individuals, upon reduction or removal of the neuroleptic, may have neural sprouting with subsequent D2 down regulation and reversal of their dyskinesia. Older individuals may not readily exhibit sprouting and D2 down-regulation, possibly accounting for a more persistent form of dyskinesia. PMID- 2906068 TI - The natural history of tardive dyskinesia. AB - Follow-up data from the first 100 patients with early dyskinesia are presented. After an average of 40.9 months, the cohort showed statistically significant decreases in tardive dyskinesia (TD) ratings. After TD onset, ratings decreased for 4 years, then plateaued and rose during the 7th year. Age was not a negative prognostic factor in this cohort. Improvement in TD correlated significantly with fewer neuroleptic-free periods before and more neuroleptic-free periods after TD onset. Neuroleptic dosage correlated negatively with improvement in trunk and dystonia ratings. Improvement in TD is the usual finding in longitudinal studies of TD cohorts. Follow-up studies of neuroleptic-treated groups with varying proportions of patients showing TD, by contrast, tend to show increased TD because new TD cases more than offset improvement. A naturalistic study with pharmacotherapy tailored to the underlying psychiatric disorder and conducted long-term from TD onset is the ideal design for investigating the natural history of TD. PMID- 2906069 TI - Double-blind carbidopa/levodopa and placebo study in tardive dyskinesia. AB - The receptor sensitivity modification theory proposed as a potential treatment for tardive dyskinesia states that dopamine sensitivity can be down-regulated by temporarily increasing dopamine levels. We present a preliminary report of a double-blind carbidopa/levodopa-placebo study based on this hypothesis. Fifteen patients completed this 20-week trial. Based on the total tardive dyskinesia scores (using the Abnormal Involuntary Movement Scale) in the beginning and end of the study, patients were grouped as improved, same or worse. The six placebo treated patients were equally represented in all three groups, but the distribution in the carbidopa/levodopa group was bimodal: five improved, four worsened, and none remained the same. This observation lends some support to the above theory. PMID- 2906070 TI - Malpractice and tardive dyskinesia: a conceptual dilemma. AB - This discussion focuses on three basic areas relevant to tardive dyskinesia (TD). The first area includes an overview of some specific acts of negligence that have been the basis for successful malpractice cases involving TD. Some of these acts of negligence include inappropriate assessment of the patient, failure to properly care for TD, and failure to obtain a proper informed consent. The second area involves the problems of uncertainty, which are particularly manifested where the only treatment available has a high benefit but a low risk of serious adverse effects. The uncertainty rests on the limited information regarding detection of the serious consequences, or cure, once the full-blown condition develops. The third involves exploring alternatives to the tort system, such as an automatic system of compensation, which might be more appropriate for dealing with an outcome such as TD. Alternative systems might be more effective in combining incentives for quality care with adequate compensation for the injured where the condition might have been avoided. PMID- 2906071 TI - Somatostatin-like immunoreactivity and glycine high-affinity uptake colocalize to an interplexiform cell of the Xenopus laevis retina. AB - Antibodies directed against somatostatin have been used to label a population of interplexiform cells (IPCs) in the Xenopus laevis retina. These cells have spherical soma which lie in the inner nuclear layer (INL), adjacent to or one cell distal to the inner plexiform layer (IPL). Processes from these cells project throughout the IPL, with a fairly dense accumulation of labeled dendrites in the upper two-fifths of the IPL and a dense, narrow band of labeled dendrites adjacent to the ganglion cell layer. These cells also have finer processes, originating at the cell body, that traverse the INL and ramify in the outer plexiform layer (OPL). Double label experiments show that all of the cells that contain somatostatin-like immunoreactivity (SOM-LI) in the INL are also labeled by high-affinity uptake with 3H-glycine. Immunocytochemistry of retinal whole mounts shows that these cells are evenly distributed across the retina at a density of 542 +/- 65 cells/mm2. On the basis of the colocalization experiments and the morphological homogeneity of these cells, we suggest that they represent a single cell type. Interplexiform cell processes were further characterized by electron microscopy after immunocytochemistry or 3H-glycine autoradiography. In the IPL, IPC processes are seen to be postsynaptic at both ribbon and conventional synapses. This input is found almost entirely in the distal two fifths of the IPL. Interplexiform cell processes are presynaptic to unlabeled processes in both the distal and proximal IPL. In the OPL, labeled processes are found near or contiguous with photoreceptor bases, and are often presynaptic to small-diameter processes. The postsynaptic processes have been identified as bipolar cell dendrites in six cases. Interplexiform cell processes may also contact horizontal cell processes in the OPL. PMID- 2906072 TI - Putative glutamatergic and/or aspartatergic cells in the main and accessory olfactory bulbs of the rat. AB - The "transmitter-specific" retrograde axonal tracer 3H-D-aspartate has been used to demonstrate neurons in the olfactory bulb which putatively utilize aspartate and/or glutamate as their neurotransmitter and which send an axon either to the piriform cortex or within the bulb itself. Injections of 3H-D-aspartate into layer I of the anterior piriform cortex, in the zone of termination of axons from the olfactory bulb, labeled only a few cells in the main olfactory bulb, located in the mitral and external plexiform layers. Although these cells resembled mitral and tufted cells, they tended to have smaller somata than other mitral or tufted cells and apparently form a distinct subpopulation of relay cells. In contrast, many of the mitral cells of the accessory olfactory bulb were labeled by the same injections of 3H-D-aspartate, probably as a result of involvement of the accessory olfactory tract or its bed nucleus in the injection site. Similar injections of the "nonspecific" tracer HRP into the anterior piriform cortex labeled most of the cells in the mitral cell layer of both the main and accessory olfactory bulbs, and some tufted cells in the external plexiform layer. It is concluded that only a small, distinct subpopulation of the mitral or tufted cells of the main olfactory bulb are aspartatergic and/or glutamatergic, while many (at least) of the mitral cells of the accessory olfactory bulb use the excitatory amino acids as transmitters. Injections of 3H-D-aspartate directly into the main olfactory bulb also failed to label the mitral and deeply situated tufted cells. However, a few cells were labeled in the periglomerular region, the superficial external plexiform layer, and the granule cell layer near the injection site. These labeled cells were smaller than mitral and tufted cells but generally larger than periglomerular or granule cells. They may represent a population of glutamatergic or aspartatergic short axon cells. In addition, small cells of an unknown type were labeled in the olfactory nerve layer following injections in the deepest part of the bulb. These cells do not correspond to any of the well characterized cell types of the olfactory bulb. PMID- 2906073 TI - In vitro and in vivo regulation of transglutaminase activity of mouse epidermal cells by various vitamin A compounds. PMID- 2906074 TI - Scanning electron microscopic appearance of Thy-1 positive dendritic epidermal cells in mouse epidermal cell suspension. PMID- 2906075 TI - Systemic bone growth factors concentrations in calves during the perinatal period. AB - Plasma somatostatin (SRIF), growth hormone (GH), somatomedin C (IGF1), osteocalcin (BGP), 1,25-dihydroxyvitamin D (1,25-(OH)2D), calcium and inorganic phosphorus were measured in 10 chronically-catheterized fetal calves and in their dams during the two last months of gestation. Thus fetal life is associated with high levels of GH (1.53 +/- 0.14 nmol.l-1), BGP (64 +/- 4 nmol), Ca (2.90 +/- 0.06 nmol.l-1) compared to the results obtained in the pregnant cows. The first week of postnatal life was associated with a tremendous increase in plasma SRIF concentration (from 36 +/- 5 to 106 +/- 15 pmol.l-1; P less than 0.01). These results agree with an intense bone growth during the end of fetal life in the bovine species. However, IG 1 might not play a major role in the regulation of fetal skeletal growth during this period. PMID- 2906076 TI - The effect of carbohydrates on the sporogenesis of Clostridium perfringens and Bacillus anthracis. AB - The authors studied the effect of a number of carbohydrates on the sporogenesis of Clostridium perfringens and Bacillus anthracis (vaccine strain STI) as probable soil factors capable of influencing the duration of survival of these causative agents in the external environment. Differences in the effect of the same sugars on the formation of spores by these microorganisms and clearly expressed sporogenesis-inhibiting effect of glucose (and also of lactose in clostridia) have been demonstrated. The analysis of the peculiarities of sporogenesis under unadjusted and stabilized pH values provides a basis for regarding the "glucose effect" as repression of sporogenesis in the given causative agent, but not as inhibition resulting from considerable acidification of the culture medium. This is essential for the soil conditions characterized by high buffer capacity. The ecological value of substances of carbohydrate nature consists in their important role in the energetics and trophicity of microbial coenoses of the soil which cannot fail reflecting on the fate of pathogenic microorganisms in the soil. PMID- 2906077 TI - Effect of glucocorticoid on prostaglandin E1 mediated cyclic AMP formation by vascular smooth muscle cells. AB - The effect of glucocorticoid on the prostaglandin E1 (PGE1)-mediated cyclic AMP (cAMP) formation by vascular smooth muscle cells (VSMC) from renal arteries (RA) was studied in rats. Dexamethasone (DEX) at concentrations ranging from 10(-10) to approximately 10(-8) mol/l dose-dependently potentiates the PGE1-mediated response. This facilitation began at 6 h and reached its maximum after 24 h of DEX administration. Aldosterone (10(-6) mol/l) did not affect the dose-response curve of PGE1. Inhibitors of protein and RNA synthesis blocked this glucocorticoid effect. The basal activity of adenylate cyclase in DEX-treated cells was twice as high as in control cells. Treatment of VSMC with DEX increased cholera toxin- and pertussis toxin-stimulated adenylate cyclase activity. DEX treatment also augments forskolin-stimulated adenylate cyclase activity. These results suggest that DEX increases PGE1-mediated cAMP formation of VSMC from RA through a mechanism that involves the induction of protein synthesis, and that the activation of the catalytic unit may play some role in this facilitating process. PMID- 2906079 TI - Alpha-adrenergic receptors in rabbit eyes. AB - The IOP and pupil response to alpha-adrenergic agonists and blockers was studied in albino rabbits. Topical ocular application of solutions of methoxamine (alpha 1) and oxymetazoline (alpha 2) caused dose-related early rises in IOP which were inhibited by pretreatment with prazosin, an alpha 1-blocker, or with yohimbine, an alpha 2-blocker. Although both prazosin and yohimbine have ocular hypotensive activity, the effect on the early IOP rise did not appear to be related to this action. Prazosin and yohimbine also inhibited the early IOP rise after treatment with clonidine, a second alpha 2-agonist. Surgically sympathectomized rabbits showed little or no hypersensitivity to methoxamine or oxymetazoline when compared to non-operated normal rabbits. However the treated ipsilateral eyes showed a much greater increase in IOP than the treated contralateral eyes. There was little difference in the IOP response between clonidine-treated ipsilateral and contralateral eyes. Methoxamine and oxymetazoline caused dose-related increases in the pupil diameter which were blocked by the nonselective alpha blocker phentolamine but not by prazosin (alpha 1) or yohimbine (alpha 2). This study suggests: 1) That the early IOP rise after treatment with alpha-agonists is due to stimulation of postsynaptic alpha 1-receptors, possibly located in superficial blood vessels in the anterior segment of the eye; 2) The mydriatic response to alpha-agonists appears to be mediated by alpha-receptors which differ from the classical alpha 1 and alpha 2 subtypes. PMID- 2906078 TI - Does B-HT 920 lower intraocular pressure in cats by interacting with alpha 2- and/or DA2 adrenoceptors? AB - Topical administration of B-HT 920 (50 micrograms) to the eyes of normal unanesthetized cats produced decreases in intraocular pressure and pupil diameter. The ocular hypotensive effect of B-HT 920 was eliminated by sympathectomy and pretreatment with sulpiride (2 mg/kg, s.c.). B-HT 920 also produced dose-related inhibition of contractions of the cat nictitans elicited by stimulating the pre- and postganglionic sympathetic trunks. B-HT 920-induced suppression of the contracting nictitans was antagonized more effectively by relatively selective DA2 antagonists, sulpiride and domperidone, than by rauwolscine, a relatively selective alpha 2-adrenoceptor antagonist. These data suggest that B-HT 920 produces ocular hypotension in the cat by interacting predominantly with DA2 receptor on peripheral sympathetic nerves. PMID- 2906080 TI - Effects of somatostatin, a somatostatin analog, neurotensin and met-enkephalin in the eye with special reference to the irritative response. AB - The effects of somatostatin, cyclo(D-Trp-Lys-Thr-Phe-Pro-Phe) acetate, a somatostatin analog, neurotensin, and met-enkephalin were studied in the rabbit eye by measuring the intraocular pressure (IOP), aqueous humor protein concentration, ocular blood flow and the pupil diameter. Somatostatin or the analog injected intracamerally (10 micrograms/eye) and infused intra-arterially (0.6-4 micrograms/min) had no significant effect on the parameters studied in normal eyes. However, somatostatin and, particularly, the analog attenuated the miotic response to a standard nociceptive stimulus consisting of topical application of 1% neutral formaldehyde. The other component parts of the irritative response were not attenuated. Intracameral injection of 1-2 micrograms neurotensin caused vasodilation in the anterior segment of the eye, a slight increase in aqueous humor protein concentration, and some decrease in IOP. Intracameral injection of 1-50 micrograms met-enkephalin had no effect on the blood-aqueous barrier, IOP or the pupil diameter. Neither did this dose of met enkephalin attenuate the miotic response to exogenous substance P. It seems likely that somatostatin and the somatostatin analog attenuate the miotic response to nociceptive stimuli by preventing the release of a substance, presumably substance P, from sensory nerves. PMID- 2906081 TI - Desensitization of beta-adrenergic receptors in corneal endothelium. AB - Corneal endothelial cells in primary culture responded to isoproterenol (Iso), epinephrine (Epi), nor-epinephrine (NE), Prostaglandins E1 and E2 (PGE1, PGE2) and forskolin by increasing cyclic AMP 61, 52, 28, 14, 10, and 176-fold, respectively, over control within a 10 minute incubation period. However, when cells were preincubated with Iso for one hour, they lost 76% of their responsiveness to a subsequent Iso challenge. Iso preincubation also decreased the effectiveness of other beta-adrenergic agonists (Epi and NE), but responses to PGE1, PGE2 and forskolin remained unchanged. The decreased cyclic AMP response was associated with a loss of beta-adrenergic binding sites. The affinity of the remaining receptors was unchanged as determined by propranolol displacement of [125I] pindolol binding. This study shows that corneal endothelial cells not only respond to beta-adrenergic stimuli, but can also regulate the magnitude and duration of their response to the hormone. PMID- 2906082 TI - Topical anti-inflammatory activity of beta 2-adrenoceptor agonists in the conjunctiva. AB - Increased microvascular permeability is believed to involve the contraction of venular endothelial cells, which results in the formation of leaking gaps in the postcapillary segment of the microvasculature. Several reports have suggested that interendothelial cell gap formation caused by permeability factors may be functionally antagonized by locally administered beta 2-adrenoceptor agonists. This represents a potentially novel approach for reducing inflammatory episodes in a variety of externally accessible tissues. The studies described herein extend these findings to the conjunctiva, where the relatively selective beta 2 adrenoceptor agonists salbutamol and terbutaline reduced the microvascular permeability response to histamine. Similarly, pretreatment with salbutamol or terbutaline inhibited the increase in conjunctival microvascular permeability associated with experimental immediate hypersensitivity, which indicates potential utility for allergic conjunctivitis. PMID- 2906083 TI - The rebound release of growth hormone (GH) following somatostatin infusion in rats involves hypothalamic GH-releasing factor release. AB - We have studied the rebound secretion of GH following short-term somatostatin (SS) infusions in conscious rats, using an automatic sampling system for withdrawing frequent microsamples of blood. Intravenous infusions of SS (5-50 micrograms/h per rat) inhibited spontaneous GH secretion, but when SS was withdrawn there was a large burst of rebound GH secretion. A sub-anaesthetic dose of urethane reduced such rebound bursts of GH, suggesting a hypothalamic involvement in rebound GH secretion. Passive immunization with an antibody against rat GH-releasing factor (GRF) attenuated the rebound GH secretory response to the withdrawal of an SS infusion (GH concentration during rebound secretion was 26 +/- 21 micrograms/l vs 475 +/- 127 micrograms/l (mean +/- S.E.M.), after 0.5 ml anti-GRF serum or non-immune serum respectively). The inhibition of GH rebound secretion was related to the dose of anti-GRF serum administered. Intravenous infusions of human GH (20-100 micrograms/h per rat) also reduced the size of the rebound GH secretion following SS withdrawal, in both male and female rats. We suggest that the rebound GH secretion that follows SS withdrawal in vivo is caused mainly by a hypothalamic release of GRF. Exogenous GH inhibits SS-induced rebound GH secretion in the conscious rat, possibly by inhibiting hypothalamic GRF release. PMID- 2906084 TI - In-vitro control of growth hormone secretion by synthetic releasing factors in young and adult ducks (Anas platyrhynchos). AB - Release of GH from perifused duckling hemipituitaries was stimulated, in a biphasic manner, by synthetic TRH and human pancreatic GH-releasing factor (GRF). At all effective concentrations, the level of GH release was increased within 5 min of TRH or GRF perifusion and was maximal after 10 min of TRH perifusion and after 20 min of GRF perifusion. Although TRH was perifused for 20 min the level of GH release declined during the last 10 min. The most effective dose of TRH (1.0 micrograms/ml; 2.7 mumol/l) and GRF (0.5 micrograms/ml; 110 nmol/l) provoked similar (250-300%) increases in the level of GH release. However, since the effect of TRH was only of short duration, the total release of GH induced by GRF was higher than that elicited by TRH, especially with the low dose. The increase in release of GH induced by TRH or GRF was blunted when pituitaries from adult ducks were used. As in young ducks, the GH response to GRF was higher, whereas the response to TRH was very low. The GH response of perifused adult pituitaries to GRF was, however, potentiated when TRH was perifused simultaneously. The basal release of GH from both young and adult pituitary glands was unaffected by perifusion with somatostatin-14 (SRIF-14) at doses of 1 and 2 micrograms/ml. The perifusion of hemipituitary glands with similar doses of SRIF-14 was also unable to suppress the stimulation of GH release induced by prior perifusion with GRF, although when SRIF-14 and TRH were simultaneously perifused TRH-induced GH release was markedly suppressed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2906085 TI - A new Apa LI restriction fragment length polymorphism in the low density lipoprotein receptor gene. AB - The existence of a new Apa LI restriction fragment length polymorphism in the third intron of the low density lipoprotein (LDL) receptor gene was described. As a gene probe we used a newly constructed derivative of pLDLR 3 which did not contain the highly repetitive Alu-sequences in exon 18. This new gene probe detected all exon sequences containing restriction fragments, and enabled us to demonstrate all described polymorphisms, which might be useful for genetic linkage studies. Based on analysis of 72 unrelated normo- and hypercholesterolaemic persons, the frequency of the allele A2, which showed the additional cutting site, was determined to be 0.05. With the simplified gene probe, pLDLR delta, we also studied other polymorphisms. A clear linkage disequilibrium between the Pvu II and Msp I polymorphisms was detected. This, and the previously described linkage disequilibrium of the two Msp I polymorphisms, demonstrate that the LDL receptor gene is apparently less heterogeneous than expected from the number of described polymorphisms. PMID- 2906086 TI - Infradian biorhythms of enzymuria in man? AB - The temporal courses of dipeptidyl peptidase IV gamma-glutamyltransferase and alanine aminopeptidase were followed over 70 days in the morning urine of 15 healthy persons. Subsequent to basic statistical analysis a two-step procedure was performed, including spectral analysis and the fit of a cosine function by non-linear regression. The excretion of the 3 enzymes followed an infradian biorhythm with a mean period length of 10.04 for dipeptidyl peptidase IV, 13.34 for gamma-glutamyltransferase and 10.17 for alanine aminopeptidase. In addition to the basic rhythmic process described by the fitted cosine functions, in most of the enzyme patterns steap peaks of very high excretory activity appeared which was verified in repeated measurements. These infradian biorhythms with changes in the range of 100% and more, as well as their interindividual variations, have to be considered in assessing the excretion of enzymes. PMID- 2906087 TI - Molecular cloning of a gene affecting the autolysin level and flagellation in Bacillus subtilis. AB - A 2.8 kb PstI fragment of Bacillus subtilis 168W DNA has been cloned into Escherichia coli HB101 and B. subtilis AG5 using pAC3 as a shuttle plasmid. The new plasmid (pBRG1), of 10.2 kb, complemented flaD mutations which show reduced production of autolysin(s), filamentation and non-motility (deficiency of flagella). Deletion experiments showed that the suppressive gene is located between the HindIII and XbaI sites (1.0 kb apart) in pBRG1. The integration of a plasmid having chloramphenicol resistance closely linked to the flaD gene into the B. subtilis AC703 chromosome and its genetic analysis indicated that the cloned fragment contained the flaD gene itself. A high-copy-number plasmid carrying the cloned gene did not lead to an increase in autolysin production above the wild-type level, but it changed the colony morphology from smooth to rough. Among several autolysin-deficient mutations, lyt-151 was suppressed only by the high-copy-number plasmid carrying the cloned gene. PMID- 2906088 TI - Topographic subtypes of tardive dyskinesia in schizophrenic patients aged less than 60 years: relationship to demographic, clinical, treatment, and neuropsychological variables. AB - There are conflicting reports about factors that may be associated with the development of involuntary movements in patients exposed to long-term neuroleptic treatment. Recent evidence suggests that some of these inconsistencies may relate to the practice of regarding these disorders as a unitary syndrome. There is also evidence that both the topographic distribution of these involuntary movements and the pathophysiological mechanisms underlying them may differ in the young and in the old. In this study, demographic, clinical, treatment and neuropsychological variables were investigated for association with the presence of orofacial and limb-truncal dyskinesias in 57 schizophrenic patients aged less than 60 years. Stepwise multiple logistic regression analysis showed that orofacial dyskinesia, at different degrees of severity, was negatively associated with positive schizophrenic syndrome and with either age at assessment or age at onset of illness. None of the indices of schizophrenic deficit (cognitive impairment, clinical defect state, behavioural deterioration, or neurological dysfunction) was related to orofacial dyskinesia. Limb-truncal involuntary movements were negatively related to current daily dosage of neuroleptics. The findings indicate that these two types of dyskinesia may involve different underlying mechanisms and that, for young schizophrenic patients, current pathophysiological or neurochemical theories of involuntary movement disorders are inadequate in explaining their origins. PMID- 2906089 TI - The effects of antipsychotic drugs and symptomatology on perceptual asymmetry in schizophrenia. AB - Perceptual asymmetry was measured in acutely psychotic schizophrenic patients and normal controls using a dichotic monitoring task. Although the schizophrenic group differed from the controls in terms of accuracy and speed of response, there were no significant group differences with respect to asymmetries in these variables. The pattern of responding in the schizophrenic group was also examined in relation to differences in symptomatology and antipsychotic drug administration. These variables, in isolation and in interaction with each other, were found to have a number of effects on both asymmetry and overall level of responding. The results were interpreted in the context of an information processing model of functional hemisphere asymmetry in schizophrenia, and the implications regarding the nature of schizophrenic symptomatology and the effects of antipsychotic drugs were discussed. PMID- 2906090 TI - Myotonic dystrophy and hyperparathyroidism: association with neurofibromatosis and multiple endocrine adenomatosis type 2A. AB - Four patients with hyperparathyroidism associated with myotonic dystrophy have been identified. All were females aged between 2 and 45 years. They were from three separate families, with two related patients being mother and daughter. In addition, one patient had medullary carcinoma of the thyroid and was diagnosed as having multiple endocrine adenomatosis, type 2A; another had an unspecified thyroid carcinoma; a third patient had neurofibromatosis. Our data suggest that myotonic dystrophy may somehow be associated with one or more of these disorders of neural crest origin. PMID- 2906091 TI - Effect of pentobarbital on gastric acid secretion elicited by secretagogues or electrical vagal stimulation in rats under urethane anesthesia. AB - The effect of pentobarbital, which stimulates gastric acid secretion in urethane anesthetized rats, on secretagogue-stimulated or electrically stimulated acid secretion was studied in the rat perfused stomach. 2-Deoxy-D-glucose (2-DG) stimulated gastric acid secretion was markedly depressed by intravenous injection of pentobarbital, but was definitely increased by lateral cerebroventricular injection and was unaffected by injection into the fourth cerebroventricle. Bethanechol-stimulated secretion was augmented by intravenous injection of pentobarbital. In vagotomized rats, pentobarbital did not affect the bethanechol stimulated or electrically vagally stimulated secretion. These findings indicate that pentobarbital produces both stimulatory and inhibitory effects on gastric acid secretion through a central mechanism, especially in the forebrain. It was proposed that the inhibitory response would result from some interaction of intravenous 2-DG and pentobarbital in the central regulatory system of gastric secretion. PMID- 2906092 TI - The D-mannose-specific lectin from Gerardia savaglia blocks binding of human immunodeficiency virus type I to H9 cells and human lymphocytes in vitro. AB - The new D-mannose-specific lectin from Gerardia savaglia is shown to prevent infection of H9 cells with human immunodeficiency virus type 1 (HIV-1; strain HTLV-IIIB). At a concentration of 0.2 microM, complete protection was achieved. Even at a 50-fold higher concentration, this lectin is not toxic for the cells. Moreover, the lectin inhibits syncytium formation in the HTLV-IIIB/H9-Jurkat cell system to 100% at 0.2 microM. This effect was abolished by coaddition of D mannose at a stoichiometric ratio of lectin to sugar of 1:500. The lectin-caused inhibition of syncytia formation was observed also in the HIV-1/human lymphocyte system. Perhaps more importantly, it is shown that the lectin reacts with the oligosaccharide side chains of the HIV-1 gp120 env molecule, which very likely can be classified to the high-mannose oligosaccharides. These data provide the basis for a rational screening for compounds interfering with gp120-CD4 interactions. PMID- 2906093 TI - Drug treatment of the hypertensive diabetic. PMID- 2906094 TI - [History of the study of Alzheimer disease and changes in the concept and the name]. PMID- 2906095 TI - [Drug therapy of Alzheimer's disease using neurotransmitter-related substances]. PMID- 2906096 TI - [Drug therapy of Alzheimer's disease. Problems and strategy in development of new therapeutic drugs for Alzheimer's disease]. PMID- 2906097 TI - [Effect of nizatidine on the 14C-aminopyrine accumulation by isolated guinea pig parietal cells]. PMID- 2906098 TI - Pharmacological studies on the selectivity of HV-723, a new alpha-1 adrenoceptor antagonist. AB - The pharmacological profile of a new alpha-1 adrenoceptor antagonist, alpha-ethyl 3,4,5-trimethoxy-alpha-(3-((2-(2-methoxyphenoxy)ethyl)amino) propyl) benzene acetonitrile fumarate (HV-723), was studied in vitro. In dog mesenteric arteries, HV-723, prazosin and yohimbine competitively inhibited noradrenaline-induced contraction: the pA2 value of HV-723 (9.37) was apparently larger than that of prazosin (8.22) and yohimbine (7.18). However, HV-723 showed no or only a slight inhibition on the contractile responses to 5-HT, KCl and prostaglandin F2 alpha. HV-723 also showed potent alpha-1 adrenoceptor antagonist activity in the dog mesenteric and saphenous veins. However, HV-723 showed little antagonist activity on the pre- and postsynaptic alpha-2 adrenoceptors, beta-1 and beta-2 adrenoceptors and muscarinic receptors. HV-723 also inhibited the sympathetic contraction induced by electrical transmural stimulation in the dog mesenteric arteries, and the inhibition of HV-723 was about 10 times more potent than that of prazosin. However, 3H-noradrenaline release evoked by electrical stimulation was not influenced by HV-723. These results clearly show that HV-723 is a potent and selective alpha-1 adrenoceptor antagonist. PMID- 2906099 TI - Effect of buflomedil [4-(1-pyrrolidinyl)-1-(2,4,6-trimethoxyphenyl)-1-butanone hydrochloride] on neurotransmitters in the striatum and substantia nigra. AB - Effect of buflomedil [4-(1-pyrrolidinyl)-1-(2,4,6-trimethoxyphenyl)-1-butanone hydrochloride] administration on central monoaminergic systems was investigated using male Wistar rats. Single administration of buflomedil (300 mg/kg, p.o.) induced a significant increase in the content of homovanillic acid without altering the content of dopamine (DA) and also caused a significant decrease in choline acetyltransferase (ChAT) activity in the corpus striatum. In addition, both L-glutamic acid decarboxylase activity (GAD) and gamma-aminobutyric acid (GABA) content showed a significant decrease in the substantia nigra following a single administration of buflomedil. These results indicate that buflomedil enhances DA turnover in the nigro-striatal DA pathway, possibly by activating nigro-striatal DA neurons, or by suppressing striatal cholinergic interneurons and/or striato-nigral GABAergic neurons. PMID- 2906100 TI - Effects of dobutamine and terbutaline on the secretion of glycoproteins from the acinar cells of the rat submandibular gland. AB - The actions of dobutamine (DOB) and terbutaline (TER) on the secretion of marker glycoprotein (GP) from the secretory cells of the glands and secretion of fluid from rat submandibular gland (SMG) were investigated in combination with two antagonists, metoprolol (MET) and ICI-118551 (ICI). The ED50 value of fluid secretion was 8.7 mg/kg for DOB and 5.9 mg/kg for TER. MET, administered prior to either agonists at a dose of 40 mg/kg, inhibited the fluid secretion. However, the blocking effects of ICI were considerably lower than those of MET. The electrophoretic profiles of GP in DOB-evoked saliva were similar to those in TER evoked saliva, and included two characteristic main bands of GP I (130 KDa) and GP IV (21.5 KDa) from the acinar cells and a minor band of GP III (31 KDa) which originated in the cells of the granular tubules. When MET was administered at a dose of 5 mg/kg prior to DOB, the intensity of band I decreased, whereas that of band III did not change. These results showed that the SMG of rats contains both beta 1- and beta 2-adrenoceptors and that beta-receptors which mediate the secretion of GP from the acinus and fluid from the gland are mainly of the beta 1 subtype. PMID- 2906101 TI - The effect of a selective phosphodiesterase inhibitor, rolipram, on muricide in olfactory bulbectomized rats. AB - In order to evaluate the potential usefulness of the drug as an antidepressant, acute and chronic effects of rolipram, a selective inhibitor of Ca2+- and calmodulin-independent cyclic AMP phosphodiesterase were investigated on muricide in olfactory bulbectomized (OB) rats. Upon single administration to OB rats, rolipram at a dosage of 1 mg/kg body weight suppressed the muricide for 2 hr after its administration. As a consequence of daily administration of rolipram, however, the incidence of muricide at 24 hr after the administration was decreased, and more than 60% of the rats did not exhibit the muricide on the 12th day. After the cessation of the administration, the incidence of the muricide returned to the initial level. The suppression of the muricide was not antagonized by several kinds of neurotransmitter blockers. Administrations of phosphodiesterase inhibitors and dibutyryl cyclic AMP as well as desipramine and clomipramine also suppressed the muricide dose-dependently. Repeated administration of desipramine also gave results similar to those of rolipram: repetition of a short suppression on the muricide was followed by the appearance of a long-lasting suppression. Differently from rolipram and desipramine, dibutyryl cyclic AMP did not cause long-lasting suppression, and even the direct effect (75% suppression) observed 30 min after its administration on the first day disappeared during its repeated administration for 14 days. From these results, rolipram was considered to show an antidepressant effect through the inhibition of Ca2+- and calmodulin-independent cyclic AMP phosphodiesterase. PMID- 2906102 TI - [The effect of nebulized beta-stimulant on the regional ventilation-perfusion ratio and blood gas analysis]. PMID- 2906103 TI - [Aorto-coronary bypass operation with IMA grafts]. PMID- 2906104 TI - [Adrenergic beta receptor blockaders with intrinsic sympathomimetic activity in the treatment of arterial hypertension]. PMID- 2906105 TI - Method for assessing the activity of drugs at beta 1- and beta 2-adrenoceptors in the same animal. AB - A method is described for assessing the selectivity of compounds for beta 1- and beta 2-adrenoceptors in vivo. The potency of selective beta-adrenoceptor agonists to increase heart rate and decrease uterine contractions in pithed rats and in isolated tissues was determined. The order of potency both in vivo (i.v. route) and in vitro was: isoprenaline greater than noradrenaline greater than salbutamol on heart rate, and isoprenaline greater than salbutamol greater than noradrenaline on uterine relaxation. Fenoterol, salbutamol, and BRL 26830A/28410, but not denopamine, (i.p.) route were more potent stimulants of uterine relaxation than of heart rate in pithed rats and in vitro. The abilities of atenolol (beta 1-selective), ICI 118551 (beta 2-selective) and propranolol (non selective between beta 1- and beta 2-adrenoceptors) to inhibit responses to isoprenaline on heart rate and uterine contractions in vivo were also assessed. The effects of isoprenaline on heart rate were selectively antagonized by atenolol while those on the uterus were selectively antagonized by ICI 118551. These results show that beta 1-adrenoceptors mediate increases in heart rate and that beta 2-adrenoceptors mediate uterine relaxation in the pithed rat. They further show that the activity of compounds at these tissues can be used to assess their selectivity for beta 1- or beta 2-adrenoceptors in vivo. PMID- 2906106 TI - Clinical analysis and results of treatment of ulcerative colitis in children. PMID- 2906107 TI - Somatostatin in the treatment of gastrointestinal diseases in children. PMID- 2906108 TI - Regional profiles of steady-state levels of cyclic nucleotides, cyclic AMP phosphodiesterase, and guanylate cyclase activities during late stages of unilateral ischemia in gerbil forebrain. AB - The present study was an extension of earlier work regarding the role of cyclic nucleotides and related enzymes during cerebral ischemia in the gerbil. Following unilateral carotid occlusion, levels of cyclic AMP and cyclic GMP were measured in four rapidly inactivated brain regions at 3, 6, and 24 hr after permanent occlusion and at 2 hr of occlusion plus 1 hr of reflow. An analysis of variance indicated significant minor fluctuations in the steady-state levels of the two cyclic nucleotides within the frontal cortex, the hippocampus, the striatum, and especially the olfactory tubercle with respect to occlusion time (3 and 24 hr) but not when comparing control vs ischemic hemispheres (except at 3 hr). Changes occurred only in animals developing neurological symptoms of ischemia. At 24 hr postocclusion the specific activity of the low-Km form of cyclic AMP phosphodiesterase was elevated especially on the ischemic side when determined in homogenates of the four brain regions. Alternatively, the high-Km form of the enzyme in the presence or absence of Ca2+-calmodulin was unchanged. Guanylate cyclase activity in tissue homogenates was not influenced by the conditions of ischemia until 24 hr had elapsed, an event likewise unique to symptomatic gerbils. The sensitivity of the enzyme to hematin-catalase was decreased in the ischemic hemispheres of the hippocampus, striatum, and olfactory tubercle. In addition, further activation of the hematin-catalase response by NaN3 was depressed in the ischemic side of the hippocampus and striatum. Taken together these and previous studies indicate that fluctuations in the steady-state levels of cyclic nucleotides that occur rather prominently during acute and to a lesser degree during prolonged ischemia are not correlated with associated changes in enzymes responsible for their synthesis and/or degradation. PMID- 2906109 TI - Inhibitory neuromodulators do not alter the course of experimental hepatic encephalopathy. AB - The neuromodulators, adenosine, serotonin, and glycine, did not alter the course of hepatic encephalopathy (HE) that followed a portacaval shunt and hepatic artery ligation in rats. The substances were instilled into the brain ventricle through an intraventricular cannula in doses that affect other aspects of behavior in the normal rat (adenosine, suppression of food intake; serotonin, loss of muscle strength and ataxia; glycine, leaning and circling). A subconvulsive dose of the glycine antagonist, strychnine, also had no effect on the course of HE. A large dose of the adenosine antagonist, caffeine, had a depressive rather than excitatory effect and shortened the time taken to induction of coma. These studies and a similar previous one with gamma aminobutyric acid (GABA) suggest that the inhibitory neuromodulators do not have a prominent role in the pathogenesis of hepatic coma. PMID- 2906110 TI - DNA sequence analysis of point mutations in traA, the F pilin gene, reveal two domains involved in F-specific bacteriophage attachment. AB - Six missense point mutations in traA (WPFL43,44,45,46,47 and 51), the gene encoding F pilin in the transfer region of the F plasmid, have been characterized for their effect on the transfer ability, bacteriophage (R17, QB and fl) sensitivity and levels of piliation expressed by the plasmid. The sequence analysis of the first five of these mutations revealed two domains in the F pilin subunit exposed on the surface of the F pilus which mediate phage attachment. These two domains include residues 14-17 (approximately) and the last few residues at the carboxy-terminus of the pilin protein. One of these mutants had a pleiotropic affect on pilus function and was thought to have affected pilus assembly. The sixth point mutant (WPFL51), previously thought to be in traA, was complemented by chimeric plasmids carrying the traG gene of the F transfer region, which may be involved in the acetylation of the pilin subunit. A traA nonsense mutant (JCFL1) carried an amber mutation near the amino-terminus which is well suppressed in SuI+ (supD) and SuIII+ (supF) strains. Neither the antigenicity of the pilin nor the efficiency of plating of F-specific bacteriophages were affected when this plasmid was harbored by either suppressor strain. A second amber mutant (JCFL25) which is not suppressible, carried its mutation in the codon for the single tryptophan in F pilin, suggesting that this residue is important in subunit interactions during pilus assembly. Two other point mutants (JCFL32 and 44) carried missense mutations in the leader sequence (positions 9 and 13) which affected the number of pili per cell presumably by altering the processing of propilin to pilin. PMID- 2906111 TI - Transcriptional unit of the murine Thy-1 gene: different distribution of transcription initiation sites in brain. AB - Structural analysis of the mouse Thy-1.2 gene has shown that the major promoter of the gene is characterized by a tissue-specific DNase I-hypersensitive site and is located within a methylation-free island. The gene is regulated at the transcriptional level, and steady-state mRNA analysis reveals that the previously reported exon Ib contributes at most 5% of the total mRNA. The major promoter uses several transcription initiation sites within a region of 100 base pairs. The frequency of usage of these sites in brain is markedly different from that in other tissues. PMID- 2906113 TI - Unlinked regulation of the sensitivity of primary glucocorticoid-inducible responses in mouse mammary tumor virus infected Fu5-5 rat hepatoma cells. AB - The enzyme tyrosine aminotransferase (TAT) is induced by unusually low concentrations of glucocorticoids in Fu5-5 cells. We have isolated clones of Fu5 5 cells infected with mouse mammary tumor virus (MMTV) in order to simultaneously compare the glucocorticoid regulation of the host cell gene, TAT, with that of another primary inducible gene, MMTV. In the two clones that were examined in detail, MMTV RNA induction occurred at 4- to 11-fold higher concentrations of dexamethasone than those needed for induction of TAT mRNA. Furthermore, the amount of agonist activity displayed by the irreversible antiglucocorticoid dexamethasone 21-mesylate was greater for the induction of TAT mRNA than for MMTV RNA. These results extend our previous observations of unequal sensitivity of induction of TAT enzyme activity in two hepatoma cell lines and show that differential glucocorticoid regulation of gene induction within the same cell can occur at a pretranslational step. The present data also indicate that the unusual properties of TAT gene induction are not shared by all primary, glucocorticoid inducible responses of the same cell and imply that additional factors mediating differential regulation of glucocorticoid-responsive genes are involved. PMID- 2906112 TI - Early retinoic acid-induced F9 teratocarcinoma stem cell gene ERA-1: alternate splicing creates transcripts for a homeobox-containing protein and one lacking the homeobox. AB - Retinoic acid (RA), the natural acidic derivative of vitamin A, can modulate the expression of specific genes and can induce some cell types, such as the murine F9 teratocarcinoma stem cell line, to differentiate in culture. As an initial step toward understanding the molecular mechanism(s) by which RA exerts these effects, we previously isolated cDNA clones for a gene, ERA-1, which has the characteristics of an early, direct target for RA. We demonstrated that RA causes a rapid, dose-dependent, and protein synthesis-independent expression of the ERA 1 gene (G. J. LaRosa and L. J. Gudas, Proc. Natl. Acad. Sci. USA 85:329-333, 1988). We now report the full-length cDNA sequence and the further characterization of this gene. The data indicate that the RA-induced 2.2- to 2.4 kilobase ERA-1 RNA species that we previously detected consists of two alternately spliced messages. One mRNA encodes a protein with a predicted mass of about 36 kilodaltons (kDa) that possesses the Hox 1.6 homeobox domain. The other mRNA encodes a truncated protein of about 15 kDa which is identical to the 36-kDa protein for 114 amino acids at the amino-terminal end but which lacks the homeobox amino acid sequence. The RA-associated increase in the ERA-1 mRNA level does not appear to be due to message stabilization, suggesting that the response is at the level of transcription. By Northern (RNA) blot analysis, the usual 2.2- to 2.4-kilobase mRNA species was also rapidly expressed in P19 teratocarcinoma cells during their differentiation to fibroblastic cells in response to RA and was detected in day 10.5 and day 13.5 mouse embryos. This result indicates that the expression of this gene is not limited to the endodermal differentiation of F9 cells. PMID- 2906114 TI - Macrophage precursors as natural killer cells against tumor cells and microorganisms. AB - Macrophage precursors cells have been isolated from spleen and liver of mice and have characterized using F4/80 antibody, their proliferative response to CSF-1 and their maturation to macrophages. These nonadherent and nonphagocytic cells exert strong killing of Yac-1 tumor cells and of various microorganisms. Transplantation of these macrophage precursors into lethally irradiated allogenic hosts restores natural killer (NK) activity within 14 days. Macrophage precursors show enhanced NK activity when activated with interleukin 2. FACS analysis of F 4/80 presorted macrophage precursors reveals about 30% of the cells coexpressing NK 1.1. and F 4/80. These data support the assumption that at least a part of the NK cell compartment is derived from the myeloid lineage. PMID- 2906115 TI - Prolactin release induced by opiate agonists, effect of glucocorticoid pretreatment in intact and adrenalectomized rats. AB - Cortisol administered at a dose of 25 mg/kg 24 h before measurements decreased the prolactin secretion induced by intraventricularly given opioids (dynorphin, beta-endorphin, Met-enkephalin or D-Met-Pro-enkephalinamide). The effect of cortisol was depressed by actinomycin D pretreatment. The cortisol-induced inhibition of the action of morphine was facilitated in adrenalectomized animals; measuring the effects of increasing doses of cortisol a maximal inhibition was obtained at a dose of 5 mg/kg. The opioid-induced corticosterone secretion was not affected 24 h after a single administration of cortisol. The present results show that the cortisol-induced inhibition of opioid-induced prolactin secretion is dependent on protein synthesis and independent of changes in drug metabolism, and of the type of opiate receptor preferentially affected by the opiate agonists employed. PMID- 2906116 TI - Tissue-specific regulation of pyroglutamate aminopeptidase II activity by thyroid hormones. AB - Among the enzymes capable of degrading thyrotropin-releasing hormone (TRH) in vitro, two pyroglutamate aminopeptidases (PGA) are specific for TRH: thyroliberinase, a seric enzyme and PGAII, a membrane-bound peptidase. The effect of thyroid hormone status on the activity of these enzymes was evaluated in serum and various tissues. Only in adenohypophysis, triiodothyronine treatment increased PGAII to 376% of control; hypothyroidism produced the reverse effect (decrease to 23% of control). As previously reported, similar changes were observed for thyroliberinase. TRH degradation at the adenohypophysis level may participate in the negative feedback control of thyroid hormones. PMID- 2906117 TI - Beta-adrenergic receptors of lymphocytes in children with allergic respiratory diseases. AB - The beta-adrenergic receptor binding sites on peripheral lymphocytes in children with bronchial asthma (n = 16) and seasonal allergic rhinitis (n = 8) were examined in comparison with normal controls (n = 18) by means of 124I cyanopindolol. The number of beta-adrenergic receptors was significantly lower in the asthmatic group (858 +/- 460/lymphocyte) than in the controls (1564 +/- 983/lymphocyte). The value (1891 +/- 1502/lymphocyte in children with allergic rhinitis was slightly higher than that in healthy controls. Of the 24 patients suffering from allergic diseases of the lower or upper airways, the bronchial histamine provocation test was performed in 21; 16 gave positive results, while 5 were negative. No difference in beta-adrenergic receptor count was found between the histamine-positive and negative patients. Neither was there any correlation between the number of beta-adrenergic receptors and the high (16/24) and low (8/24) serum IgE concentrations found in allergic patients. The significant decrease in beta-adrenergic receptor count in asthmatic children lends support to Szentivanyi's concept. Further qualitative and quantitative analysis of lymphocyte beta-adrenergic receptors may provide an individual approach to the treatment of bronchial asthma with beta-sympathomimetic drugs. PMID- 2906118 TI - CHOP regimen versus intermittent chlorambucil-prednisone in stage B chronic lymphocytic leukemia. Short term results from a randomized clinical trial. French Cooperative Group on Chronic Lymphocytic Leukemia. AB - In 1985, the French Cooperative Group on Chronic Lymphocytic Leukemia started a protocol based on the (A, B, C) staging system. This paper reports the first interim results in stage B patients who were randomized to receive either the CHOP regimen or intermittent chlorambucil plus prednisone. Out of the 199 stage B patients, randomized on the reference date of May 1 1988, 94 received chlorambucil plus prednisone (7 deaths) and 105 the CHOP regimen (6 deaths). Among the evaluable patients at the 6-month examination, 53% reached clinical remission or stage A in the chlorambucil-prednisone group while 77% died in the CHOP group (p = 0.002). This short-term result supports the effectiveness of the CHOP regimen previously demonstrated by group in stage C patients. More follow-up is needed to assess the benefit from the CHOP regimen in terms of survival in stage B patients. PMID- 2906119 TI - Allergic contact dermatitis to Bryozoa and photosensitivity. PMID- 2906120 TI - The genomics of human homeobox-containing loci. PMID- 2906121 TI - Modulation of chondroblast phenotype by transforming growth factor-beta. PMID- 2906122 TI - [Significance of pulmonary APUD cells in the morphogenesis of bronchiectasis in children]. PMID- 2906123 TI - Processing and secretion of prosomatostatin by the pig pancreas. AB - Antisera and radioimmunoassays against five different regions of prosomatostatin (proSS) were used for chromatographical analysis and for immunohistochemical mapping of the products of proSS in the pig pancreas. Secreted products of proSS were studied by analysis of effluent from isolated perfused pig pancreas obtained during isoproterenol stimulation. All cells that were stained with one antiserum also stained with the other antisera. Immunoreactive nerves were not observed. Isoproterenol increased equally the secretion of proSS 20-36, proSS 65-76, and proSS 79-92 immunoreactivity. The major molecular forms identified in pancreatic extracts and released from the pancreas were proSS 79-92; proSS 65-76; an N terminally extended form of proSS 65-76; and two larger forms comprising the proSS 20-36 sequence (but not the 1-13 sequence) with and without the proSS 65-76 sequence. ProSS 1-10, 1-32 and 65-92 (somatostatin 28) were not identified. PMID- 2906124 TI - Identification by immunoblotting of somatostatin proforms in a rat pancreatic cell line. AB - The immunoblotting technique is applied to the analysis of "somatostatin" compounds secreted by R.I.N. T3 cells. We can confirm that two proforms of 15,300 +/- 750 and 29,000 +/- 1,100 Da accumulate in the extracellular medium. The unexpected form of 29 kDa, probably a dimeric form, disappears in reducing conditions. However, the 15 kDa peptide is characterized by several antibodies directed against either the intramolecular cycle of somatostatin-14 or the N terminal extension of somatostatin-28. The 15 kDa form presents the same electrophoretic mobility in SDS-PAGE than the prosomatostatin isolated from a hypothalamic extract. Furthermore, this compound corresponds to the calculated mass of 10,388 Da deduced from the cDNA sequence. The detection of an immunoreactive 6 kDa peptide in the gel filtration fractions suggests an intermediate step in the prosomatostatin processing in these cells. PMID- 2906125 TI - Simultaneous assessment of prohormone transport and processing in four separate islet cell types: a combined autoradiographic and biochemical study. AB - This study was performed to assess the relationships between prohormone transport and processing in separate cell types in pancreatic islet tissue. Anglerfish islets were subjected to pulse-chase incubation with [3H]tryptophan and/or [35S]cysteine. Tissue and media were removed at specific time points during the incubation and prepared for electron microscopic examination or biochemical analysis. Specific islet cell types were identified ultrastructurally using protein A gold immunocytochemistry. Transport of newly synthesized peptides through specific subcellular compartments was monitored using electron microscopic autoradiography. Prohormone-product ratios were established by gel filtration and high-performance liquid chromatography analyses of tissue extracts. Complete analyses were performed on A-cells (source of proglucagon-II, glucagon-II, and glucagon-like peptide-II), B-cells (proinsulin and insulin), D cells (prosomatostatin-II and somatostatin-28), and S-cells (prosomatostatin-I and somatostatin-14). Transport of newly synthesized peptides proceeded from rough endoplasmic reticulum (RER) to Golgi complex and then to mature secretory granules in all cell types. The transport rate was most rapid in A- and B-cells, slower in S-cells, and slowest in D-cells. The T1/2 for conversion of prohormone to product(s) was shortest in S-cells (150 min), slightly longer in B-cells (155 min), much longer in D-cells (259 min), and greater than 300 min in A-cells. These results demonstrate that the transport/prohormone conversion relationships are unique in each of the islet cell types monitored. PMID- 2906126 TI - A case of somatostatinoma: responses to food and SMS 201-995 administration. AB - Plasma somatostatin response to food and the administration of the long-acting somatostatin analogue SMS 201-995, as well as pituitary responses to insulin induced hypoglycemia, growth hormone-releasing hormone (GHRH) and thyrotropin releasing hormone (TRH), were assessed in a 60-year-old woman with biopsy-proven metastatic somatostatinoma. SMS 201-995 alone did not change plasma somatostatin like immunoreactivity (SRIF), but levels of low-molecular-weight forms (SRIF-14 and SRIF-28) more than doubled in response to a standard meal. This postprandial response was not affected by pretreatment with SMS 201-995. Although a growth hormone response to insulin-induced hypoglycemia and supramaximal GHRH was absent, the patient's thyroid-stimulating hormone response to TRH was normal. These results suggest that somatostatin analogues may not influence tumor autonomy and that a SRIF response to food may contribute to early satiety in patients with somatostatinoma. In addition, the long-term use of somatostatin analogues to suppress hormone production by other peptide-secreting tumors may not have predictable results. PMID- 2906127 TI - Evidence for the dependence of arterial haemostasis on ADP. AB - The possible involvement of adenosine diphosphate (ADP) in haemostatic platelet aggregation was investigated by determining the duration of primary haemorrhage as standardized bleeding times from punctures of small mesenteric arteries in anaesthetized rats. The bleeding times were highly significantly increased by infusing into the mesenteric arterial blood flowing towards the punctures either the nucleotide-dephosphorylating enzyme apyrase or the ADP-receptor antagonists ATP, adenosine 5'-(beta,gamma-methylene)triphosphonate (AMP-PCP) or 2 methylthioadenosine 5'-(beta,gamma-methylene)triphosphonate (2-MeS-AMP-PCP). The increases in bleeding times could not be accounted for by local vasodilator effects of the agents. It is concluded that the presence of ADP through local release and/or formation at sites of vascular injury contributes significantly to haemostasis, presumably by accelerating platelet aggregation. PMID- 2906128 TI - Mathematical analysis of transport and exchange in skeletal muscle. AB - A new approach to modelling microcirculatory transport and exchange is introduced and developed with specific reference to skeletal muscle. The objective is to describe the large-scale interaction of a great number of differently perfused capillary groups and to interpret phenomena observed in a whole organ in terms of processes occurring within individual capillaries. We consider fluid exchange and the associated macromolecular transport, the exchange of small metabolites carried in the plasma, and oxygen transport to tissue. PMID- 2906129 TI - A mathematical model for the freezing process in biological tissue. AB - A mathematical model has been developed to study the process of freezing in biological organs. The model consists of a repetitive unit structure comprising a cylinder of tissue with an axial blood vessel (Krogh cylinder) and it is analysed by the methods of irreversible thermodynamics. The mathematical simulation of the freezing process in liver tissue compares remarkably well with experimental data on the structure of tissue frozen under controlled thermal conditions and the response of liver cells to changes in cooling rate. The study also supports the proposal that the damage mechanism responsible for the lack of success in attempts to preserve tissue in a frozen state, under conditions in which cells in suspension survive freezing, is direct mechanical damage caused by the formation of ice in the vascular system. PMID- 2906130 TI - The Croonian lecture, 1988. Inositol lipids and calcium signalling. AB - The response of cells to many external stimuli requires a decoding process at the membrane to transduce information into intracellular messengers. A major decoding mechanism employed by a variety of hormones, neurotransmitters and growth factors depends on the hydrolysis of a unique inositol lipid to generate two key second messengers, diacylglycerol and inositol 1,4,5-trisphosphate (Ins(1,4,5)P3). Here I examine the second messenger function of Ins(1,4,5)P3 in controlling the mobilization of calcium. We know most about how this messenger releases calcium from internal reservoirs but less is known concerning the entry of external calcium. One interesting possibility is that Ins(1,4,5)P3 might function in conjunction with its metabolic product Ins(1,3,4,5)P4 to control calcium entry through a mechanism employing a region of the endoplasmic reticulum as a halfway house during the transfer of calcium from outside the cell into the cytoplasm. The endoplasmic reticulum interposed between the plasma membrane and the cytosol may function as a capacitor to insure against the cell being flooded with external calcium. When stimulated, cells often display remarkably uniform oscillations in intracellular calcium. At least two oscillatory patterns have been recognized suggesting the existence of separate mechanisms both of which may depend upon Ins(1,4,5)P3. In one mechanism, oscillations may be driven by periodic pulses of Ins(1,4,5)P3 produced by receptors under negative feedback control of protein kinase C. The other oscillatory mechanism may depend upon Ins(1,4,5)P3 unmasking a process of calcium-induced calcium release from the endoplasmic reticulum. The function of these calcium oscillations is still unknown. This Ins(1,4,5)P3/calcium signalling system is put to many uses during the life history of a cell.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2906131 TI - Intraindividual tissue-specific variations in organization of genes coding for the Na,K-ATPase subunits. PMID- 2906132 TI - Interaction between palytoxin and purified Na, K-ATPase. PMID- 2906133 TI - Two-sided functional Na,K-ATPase-liposomes for characterizing the permeability and side of action of pump inhibitors. PMID- 2906134 TI - Synthesis and pharmacological effect of substituted phenyl-4-(2 chloroethyl)tetrahydro-1,4-oxazine hydrochlorides. AB - Substituted phenyl-4-(2-chloroethyl)tetrahydro-1,4-oxazine hydrochlorides were prepared by treating the corresponding amino alcohols with thionyl chloride. Since these compounds are considered to be monofunctional 2-haloalkylamine type agents, they were tested for possible alpha-adrenergic blocking activity using the rat anococcygeus muscle. The pharmacological action of this series of compounds is discussed. PMID- 2906135 TI - Inositol lipids and transmembrane signalling. Papers from a meeting. 2 and 3 December 1987. PMID- 2906136 TI - Inositol lipids: receptor-stimulated hydrolysis and cellular lipid pools. AB - Our current knowledge of the process by which receptors stimulate the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) has its origin in the discovery by Hokin & Hokin (J. biol. Chem. 263, 967 (1953] that some pancreatic secretagogues not only elicit exocrine secretion but also stimulate the metabolism of membrane phospholipids. Despite the recent elucidation of many aspects of this widespread signalling system, there is still little information on the control of the supply of its substrate, PtdIns(4,5)P2. In particular, some studies have suggested that inositol-lipid-mediated signalling involves much or all of the inositol lipid complement of the stimulated cells, whereas other observations have equally clearly implicated the receptor-activated hydrolysis of an inositol phospholipid pool that comprises only a small fraction of the total cellular complement of these lipids. These studies, which have largely employed radiochemical analyses using single isotopes, are briefly reviewed. In addition, we report the first information obtained by a new procedure for analysing the metabolic characteristics of the inositol lipids that are broken down during stimulation. This technique employs cells that are doubly labelled in the inositol moiety of their lipids (to isotopic equilibrium with 14C and only briefly with 3H) to search for functional metabolic heterogeneity among the inositol lipids of stimulated cells. Using this method, we have found that the inositol phosphates liberated in stimulated cells during brief stimulation of V1a vasopressin receptors or prostaglandin F2 alpha receptors come from phospholipid that has a turnover rate typical of the bulk of the cellular inositol lipids. PMID- 2906137 TI - G-proteins, the inositol lipid signalling pathway, and secretion. AB - The formation of the second messenger cyclic AMP (cAMP) is known to be coupled to its receptor via a guanine nucleotide regulatory protein, GS. Ca2+-mobilizing receptors stimulate the hydrolysis of phosphatidylinositol bisphosphate (PtdIns(4,5)P2), which generates two intracellular signals Ins(1,4,5)P3 and diacylglycerol. We review the evidence that this signalling system is also composed of three types of proteins: receptor, G-protein and effector. The G protein that couples to the effector, polyphosphoinositide phosphodiesterase (PPI PDE), is a novel G-protein, GP, which is a substrate for pertussis toxin in some cells (e.g. neutrophils and platelets) but not others (e.g. pancreatic acinar cells and GH3 cells). This implies that GP is not a single G-protein but encompasses a family of proteins that can activate PPI-PDE. We have also identified a role for another G-protein, GE, which is involved in the secretory process in mast cells and neutrophils. In this case, neither the receptor nor effector has been identified and the main evidence for proposing this second G protein is based on the ability of guanine nucleotide analogues (e.g. GTP gamma S) to stimulate secretion independently of PPI-PDE activation. PMID- 2906138 TI - Receptor and G-protein-dependent regulation of turkey erythrocyte phosphoinositidase C. AB - Several lines of experimental evidence indicate the involvement of a guanine nucleotide-dependent protein (G-protein) in the hormone-stimulated hydrolysis of phosphatidylinositol(4,5)-bisphosphate (PtdIns(4,5)P2). However, the shortcomings of available procedures for cell-free assay of hormone-stimulated phosphoinositidase C (PIC) have limited our current understanding of the molecular and mechanistic details of PIC regulation. We recently have proposed that turkey erythrocyte membranes may provide a valuable model system for studies of G-protein-dependent PtdIns(4,5)P2 hydrolysis. The membranes can be simply prepared from [3H]inositol-labelled erythrocytes and they contain a PIC activity that hydrolyses endogenous phosphoinositides and is exquisitively sensitive to guanine nucleotides. PtdIns(4,5)P2 is the principal substrate for this enzyme, there being relatively little direct hydrolysis of phosphatidylinositol 4 phosphate and no detectable hydrolysis of PtdIns. The membranes also contain a purinoceptor of the P2y subclass that is efficiently coupled to PtdIns(4,5)P2 hydrolysis both in intact cells and in the isolated membranes. 2 Methylthioadenosine trisphosphate (2-methyl-S-ATP), a specific P2y receptor agonist, has no effect upon PtdIns(4,5)P2 hydrolysis in the absence of guanine nucleotides, but greatly enhances both the potency and efficacy of PIC activation by guanine nucleotides such as GTP gamma S. GTP gamma S alone stimulates PIC activity only after a prolonged time-lag; the effect of increasing doses of 2 methyl-S-ATP is progressively to shorten this lag phase. These results suggest that the mechanism of G-protein activation involves acceleration of a nucleotide exchange reaction as has been demonstrated for the activation of adenylate cyclase in the same membrane preparation. As well as contributing valuable information on the substrate specificity of PIC and its mode of regulation by hormones, turkey erythrocytes provide a plentiful source of plasma membranes and may be useful for purification of the appropriate G-protein and PIC activities. PMID- 2906139 TI - Inositol phosphates: proliferation, metabolism and function. AB - After the initial discovery of receptor-linked generation of inositol(1,4,5)trisphosphate (Ins(1,4,5)P3) it was generally assumed that Ins(1,4,5)P3 and its proposed breakdown products inositol(1,4)bisphosphate (Ins(1,4)P2) and Ins1P, along with cyclic inositol monophosphate, were the only inositol phosphates found in significant amounts in animal cells. Since then, three levels of complexity have been introduced. Firstly, Ins(1,4,5)P3 can be phosphorylated to Ins(1,3,4,5)P4, and the subsequent metabolism of these two compounds has been found to be intricate and probably different between various tissues. The functions of Ins(1,4,5)P3 and Ins(1,3,4,5)P4 are almost certainly to regulate cytosolic Ca2+ concentrations, but the reasons for the labyrinth of the metabolic pathways after their deactivation by a specific 5-phosphatase remain obscure. Secondly, inositol pentakis- and hexakisphosphates have been found in many animal cells other than avian erythrocytes. It has been shown that their synthesis pathway is entirely separate from the inositol phosphates discussed above, both in terms of many of the isomers involved and probably in the subcellular localization; some possible functions of InsP5 and InsP6 are discussed here. Thirdly, cyclic inositol polyphosphates have been reported in stimulated tissues; the evidence for their occurrence in vivo and their possible physiological significance are also discussed. PMID- 2906140 TI - Regulation of platelet phospholipase C. AB - We have investigated factors affecting the activation of phospholipase C in human platelets. Prior exposure of platelets to phorbol esters that stimulated protein kinase C inhibits the activation of phospholipase C in response to a variety of receptor-directed agonists, including alpha- and gamma-thrombin and thromboxane A2 analogues. Such activation has been assayed by measurements of accumulated InsP3 (including Ins(1,4,5)P3 and Ins(1,3,4)P3) and PtdOH. Inhibition is not overcome by Ca2+ ionophores, and substances that block or mimic Na+-H+ exchange neither block nor mimic these inhibitory effects. Cyclic AMP and cyclic GMP, other agents known to inhibit phospholipase C activation, do not accumulate in platelets exposed to phorbol esters. Although a portion of the effects of phorbol ester on InsP3 accumulation may be explained by 5-phosphomonoesterase activity, it is likely that more direct effects on phospholipase C are being exerted as well, and contribute the major inhibitory route. We have examined the susceptibility of adenylyl cyclase-associated Gi and 'Gp'-activated phospholipase C to inhibitory ADP-ribosylation by pertussis toxin-derived enzyme (S1 protomer) administered to saponin-permeabilized platelets. The effects of alpha-thrombin on adenylyl cyclase can be inhibited by up to 50% by S1, at which point inhibition of phospholipase C is barely detectable. Thromboxane A2 analogues, which do not affect adenylyl cyclase (Gi), stimulate phospholipase C; this effect is not impaired by S1. We therefore propose that the inhibitory effects of phorbol esters on the activation of phospholipase C are not mediated primarily by effects on Gi. PMID- 2906141 TI - The heterogeneity and differential expression of protein kinase C in nervous tissues. AB - Protein kinase C exists as a large family of multiple subspecies with subtle individual characteristics. This heterogeneity comes from different genes as well as from different splicings of a single RNA transcript. The members of this family have closely related structures with a high degree of homology. Biochemical studies have shown that their mode of activation and kinetic and catalytic properties differ slightly from one another. By using a combination of biochemical and immunocytochemical techniques, their differential regional and cellular expression have been shown in the nervous tissues. Each member of this enzyme family may have a specialized function in transducing various physiological and pathological signals into different cell types. PMID- 2906142 TI - Spatial and temporal aspects of cell signalling. AB - As new techniques are developed to measure intracellular messengers it becomes increasingly apparent that there is a remarkable spatial and temporal organization of cell signalling. Cells possess a small discrete hormone-sensitive pool of inositol lipid. In some cells such as Xenopus oocytes and Limulus photoreceptors this phosphoinositide signalling system is highly concentrated in one region of the cell, so establishing localized calcium gradients. Another example is the hydrolysis of inositol lipids in eggs at the point of sperm entry resulting in a localized increase in Ins(1,4,5)P3 and calcium which spreads like a wave throughout the egg. In hamster eggs this burst of calcium at fertilization recurs at 1-3 min intervals for over 100 min, a particularly dramatic example of spontaneous activity. Spontaneous oscillations in intracellular calcium exist in many different cell types and are often induced by agonists that hydrolyse inositol lipids. We have made a distinction between oscillations that are approximately sinusoidal and occur at a higher frequency where free calcium is probably continuously involved in the oscillatory cycle and those where calcium falls to resting levels for many seconds between transients. In the former case, the oscillations are thought to be induced through a cytoplasmic oscillator based on the phenomenon of calcium-induced calcium release. Such oscillations can be induced in Xenopus oocytes after injection with Ins(1,4,5)P3. A receptor controlled oscillator based on the periodic formation of Ins(1,4,5)P3 is probably responsible for the generation of the widely spaced calcium transients. The function of such calcium oscillations is currently unknown. They may be a reflection of the feedback interactions that operate to control intracellular calcium. Another possibility emerged from observations that in some cells the frequency of calcium oscillations varied with agonist concentration, suggesting that cells might employ these oscillations as a way of encoding information. One advantage of using such a frequency-dependent mechanism may lie in an increase in fidelity, especially at low agonist concentrations. Whatever these functions might be, it is clear that uncovering the mechanisms responsible for such oscillatory activity will greatly enhance our understanding of the relation between the phosphoinositides and calcium signalling. PMID- 2906143 TI - The function of glycosyl phosphoinositides in hormone action. AB - The molecular events involved in the cellular actions of insulin remain unexplained. Some of the acute actions of the hormone may be due to the intracellular generation of a chemical substance which modulates certain enzyme activities. Such an enzyme-modulating substance has been identified as an inositol phosphate-glycan, produced by the insulin-sensitive hydrolysis of a glycosyl-phosphatidylinositol (glycosyl-PtdIns) precursor. This precursor glycolipid is structurally similar to the glycosyl-phosphoinositide membrane protein anchor. The exposure of fat, liver or muscle cells to insulin results in the hydrolysis of glycosyl-PtdIns, giving rise to the inositol phosphate glycan and diacylglycerol. This hydrolysis reaction is catalysed by a glycosyl-PtdIns specific phospholipase C. This enzyme has been characterized and purified from a plasma membrane fraction of liver. This reaction also results in the acute release of certain glycosyl-PtdIns-anchored proteins from the cell surface. Elucidation of the functional role of glycosyl-phosphoinositides in the generation of second messengers or the release of proteins may provide further insights into the pleiotropic nature of insulin action. PMID- 2906144 TI - The localization of calcium release by inositol trisphosphate in Limulus photoreceptors and its control by negative feedback. AB - Microvillar photoreceptors of invertebrates exhibit a light-induced rise in the intracellular concentration of free calcium (Cai) that results in part from release of calcium from an intracellular compartment. This light-induced release of calcium appears to result from a cascade of reactions that involve rhodopsin, a GTP-binding protein and a phospholipase-C which releases inositol 1,4,5 trisphosphate (Ins(1,4,5)P3) from the plasma membrane; the Ins(1,4,5)P3 acts to release calcium from smooth endoplasmic reticulum. In the ventral photoreceptor of the horseshoe crab Limulus polyphemus not all of the endoplasmic reticulum is subject to calcium release by Ins(1,4,5)P3. Only endoplasmic reticulum in the light-sensitive region of the cell is competent to release calcium in response to Ins(1,4,5)P3. The release of calcium by Ins(1,4,5)P3 in ventral photoreceptors appears to be subject to feedback inhibition through elevated Cai. We suggest that this feedback inhibition contributes to sensory adaptation in the photoreceptor and may account for oscillatory membrane responses sometimes observed with large injections of Ins(1,4,5)P3. PMID- 2906145 TI - Neural function: metabolism and actions of inositol metabolites in mammalian brain. AB - In the nervous system, a variety of cell types respond to external stimuli through the inositol lipid signalling pathways. The stimulus-coupled sequence of intracellular events has been investigated in a homogeneous model system, the cloned mammalian neural cell line NG115-401L. The neural peptide bradykinin stimulates a rapid production of identified inositol phosphate isomers and an intracellular Ca2+ discharge followed by a persistent plasma membrane influx. The temporal sequence suggests that Ins(1,4,5)P3 or Ins(1,3,4,5)P4 or both may coordinate these events in a neuronal cell, as has been suggested in other cell types. Thapsigargin, an irritant and tumour-promoting plant product, produces calcium transients in the absence of inositol phosphate production, and may provide a new tool for investigating the interactions between inositol phosphates and changes in cellular calcium homeostasis. In the 401L line, high levels of radiolabelled InsP5 and InsP6 have been detected, which has led to the evaluation of their possible occurrence and actions in normal brain. Both InsP5 and InsP6 are produced from a radiolabelled myo-inositol precursor in intact mature brain in a region-specific manner. This suggests that both inositol polyphosphates may be end products of regionally regulated biosynthetic pathways. When microinjected into a nucleus of the brainstem, or iontophoretically applied to the dorsal horn of the spinal cord, both InsP5 and InsP6, but not Ins(1,3,4,5)P4 isomers, appear to be potent neural stimulants. These results suggest that the inositol lipid signalling pathways may generate both intracellular and extracellular signals in brain. PMID- 2906146 TI - Inositol trisphosphate, calcium and muscle contraction. AB - The identity of organelles storing intracellular calcium and the role of Ins(1,4,5)P3 in muscle have been explored with, respectively, electron probe X ray microanalysis (EPMA) and laser photolysis of 'caged' compounds. The participation of G-protein(s) in the release of intracellular Ca2+ was determined in saponin-permeabilized smooth muscle. The sarcoplasmic reticulum (SR) is identified as the major source of activator Ca2+ in both smooth and striated muscle; similar (EPMA) studies suggest that the endoplasmic reticulum is the major Ca2+ storage site in non-muscle cells. In none of the cell types did mitochondria play a significant, physiological role in the regulation of cytoplasmic Ca2+. The latency of guinea pig portal vein smooth muscle contraction following photolytic release of phenylephrine, an alpha 1-agonist, is 1.5 +/- 0.26 s at 20 degrees C and 0.6 +/- 0.18 s at 30 degrees C; the latency of contraction after photolytic release of Ins(1,4,5)P3 from caged Ins(1,4,5)P3 is 0.5 +/- 0.12 s at 20 degrees C. The long latency of alpha 1-adrenergic Ca2+ release and its temperature dependence are consistent with a process mediated by G-protein-coupled activation of phosphatidylinositol 4,5 bisphosphate (PtdIns(4,5)P2) hydrolysis. GTP gamma S, a non-hydrolysable analogue of GTP, causes Ca2+ release and contraction in permeabilized smooth muscle. Ins(1,4,5)P3 has an additive effect during the late, but not the early, phase of GTP gamma S action, and GTP gamma S can cause Ca2+ release and contraction of permeabilized smooth muscles refractory to Ins(1,4,5)P3. These results suggest that activation of G protein(s) can release Ca2+ by, at least, two G-protein-regulated mechanisms: one mediated by Ins(1,4,5)P3 and the other Ins(1,4,5)P3-independent. The low Ins(1,4,5)P3 5-phosphatase activity and the slow time-course (seconds) of the contractile response to Ins(1,4,5)P3 released with laser flash photolysis from caged Ins(1,4,5)P3 in frog skeletal muscle suggest that Ins(1,4,5)P3 is unlikely to be the physiological messenger of excitation-contraction coupling of striated muscle. In contrast, in smooth muscle the high Ins(1,4,5)P3-5 phosphatase activity and the rate of force development after photolytic release of Ins(1,4,5)P3 are compatible with a physiological role of Ins(1,4,5)P3 as a messenger of pharmacomechanical coupling. PMID- 2906147 TI - Roles for the phosphatidylinositol cycle in early development. AB - Founded on the seminal studies and writings of Hokin, Michell and Berridge, a vast body of data now exists documenting the central importance of phosphatidylinositol (PtdIns) cycle activation in transducing information of many types across the plasma membrane. The great majority of these data derive from studies of terminally differentiated somatic cells. Nevertheless, the fact that many crucial events in animal development also involve transduction of information across the plasma membrane has recently led developmental biologists to search for regulatory roles for PtdIns cycle activity in such developmental processes as oocyte maturation, fertilization, and embryogenesis, with encouraging results. In this paper I briefly review the progress of such studies, beginning with the event in which the PtdIns cycle's role is best understood (fertilization), then progressing both backwards and forwards in developmental time to explore more speculative roles for the PtdIns cycle in oocyte maturation and pattern formation during embryogenesis. PMID- 2906148 TI - Transmembrane signalling pathways initiating cell growth in fibroblasts. AB - The mechanisms of growth factor action were studied in a fibroblastic cell line capable of reversible growth arrest in G0-G1. This cell line, derived from Chinese hamster lung, can be stimulated to divide by a limited set of purified growth factors, including EGF, FGF, PDGF, alpha-thrombin (THR), serotonin (5-HT) and insulin. THR and 5-HT stimulate, via a G-protein (Gp), a polyphosphoinositide specific phospholipase C (PtdIns(4,5)P2-PLC). In contrast, the mitogens EGF, FGF, PDGF, and insulin do not stimulate PtdIns(4,5)P2-PLC unless this pathway has been preactivated by THR or AlF-4. Finally, from the specific inhibitory action of pertussis toxin on THR- and 5-HT-induced DNA synthesis, and from the exploitation of the 5-HT pharmacological tools, we conclude that: (i) there are at least two distinct G-proteins involved in signalling growth: Gp, coupling receptors to PtdIns(4,5)P2-PLC, and Gi, coupling receptors negatively to adenylyl cyclase and probably to other unknown effector(s); (ii) activation of receptor-tyrosine kinases provides an alternate growth factor signalling pathway, independent of Gp and Gi-mediated actions; and (iii) tyrosine kinases positively 'cross communicate' with the inositol-lipid pathway (phosphorylation of Gp, PLC, PtdIns kinases...?). PMID- 2906150 TI - Glutamate-induced K+ flux in the photoreceptor layer of isolated retina of cyprinid fish: possible consequences for second-order neurones. AB - The effect of L-glutamate on extracellular K+ activity (aK0) in the micro environment of the isolated retina of a cyprinid fish was investigated using double-barrelled K+-sensitive micro-electrodes. Glutamate was pulsed onto the retina from an atomizer, and aK0's recorded at different retinal depths. Glutamate induced a concentration-dependent rise in aK0 which was maximal in the first 100 microns of the retinal surface. The aK0 change was transient, with a time to peak of 20-30 s, and complete reversal within 4 min. However, if the retina was pre-treated with dinitrophenol or ouabain, the maximum rise in aK0 was greater than normal, and the effect was sustained. Application of equimolar glutamate transiently depolarized the membrane potentials of horizontal cells. The effects of glutamate on aK0 and horizontal cell membrane potential had some common characteristics. It is concluded that glutamate may have non-synaptic effects on post-receptoral retinal neurones, and possible mechanisms of this are considered. PMID- 2906149 TI - Behavioral effects of acute hexamethonium in rats chronically intoxicated with nicotine. AB - To investigate the effects of chronic nicotine administration on feeding behavior, hexamethonium, a nicotinic blocker with mainly peripheral actions, was acutely given to rats during and after chronic nicotine administration. Nicotine decreased both the time spent investigating the food and the amount of food consumed. It also decreased the time spent rearing and grooming and increased the time spent resting. These behaviors returned to control levels after nicotine withdrawal. During nicotine administration, 10 mg/kg of hexamethonium increased the amount of time the nicotine-treated rats spent investigating the food but did not change the amount of food actually eaten. These data show that predominantly peripheral nicotinic blockade can partially alleviate the effects of chronic nicotine administration of feeding behavior, suggesting that at least some of the effects of nicotine on feeding are peripheral. The finding that the investigational and consummatory aspects of feeding behavior can be pharmacologically differentiated implies that some aspects of their neural control may be distinct. PMID- 2906151 TI - Biosynthesis of peptide neurotransmitters: studies on the formation of peptide amides. AB - A high proportion of peptide transmitters and peptide hormones terminate their peptide chain in a C-terminal amide group which is essential for their biological activity. The specificity of an enzyme that catalyses the formation of the amide was investigated with the aid of synthetic peptide substrates. With peptides containing l-amino acids the enzyme exhibited an essential requirement for glycine in the C-terminal position; amidation did not take place with peptides that had leucine, alanine, glutamic acid, lysine or N-methylglycine at the C terminus and a peptide extended by the attachment of lysine to the C-terminal glycine did not act as a substrate. Amidation did occur with a peptide containing C-terminal D-alanine but no reaction was detected with peptides having C terminal, D-serine or D-leucine. In tripeptides with a neutral amino acid in the penultimate position, amidation, took place readily but the reaction was slower when this position was occupied by an acidic or a basic residue. A series of overlapping peptides with C-terminal glycine, based on partial sequences of calcitonin, underwent amidation at similar rates, indicating that the amidating enzyme recognizes only a limited sequence at the C-terminus of its substrates. The results provide evidence that the amidating enzyme has a highly compact substrate binding site. PMID- 2906152 TI - Differences in the cataleptogenic actions of SCH23390 and selected classical neuroleptics. AB - In an attempt to understand the nature of the interactions between D1 and D2 dopamine subsystems as well as between dopamine and acetylcholine, catalepsy was assessed in rats following various drug treatments. The D1-specific antagonist SCH23390 (0.1 mg/kg) produced prompt, potent and brief (less than 90 min) catalepsy with an ED50 of 0.105 mg (0.3 mumol)/kg. Conversely, fluphenazine (0.1 mg/kg), spiroperidol (0.1 mg/kg), and haloperidol (0.2 mg/kg) all had comparably potent but more slowly rising and prolonged (greater than 240 min) effects. The action of SCH23390 was synergistic with spiroperidol, inhibited by apomorphine or atropine, unaffected by mecamylamine, and markedly potentiated by pilocarpine. However, pilocarpine was unable to significantly potentiate the action of fluphenazine or spiroperidol. It is inferred that SCH23390 differs from the classical neuroleptics in its mechanism of cataleptogenicity, that there is a cholinergic link with the D1 dopamine system, and further, that there may be a difference in the nature or impact of the cholinergic interaction with the D1 and D2 dopamine systems. PMID- 2906153 TI - Neuroendocrine evidence for serotonin receptor hypersensitivity in panic disorder. AB - Normal controls (NC) (n = 15), patients with panic disorder (PD) (n = 13) and patients with major depression (MD) (n = 17) were challenged with a single, oral dose (0.25 mg/kg) of the selective 5HT agonist m-chlorophenyl-piperazine (MCPP) or placebo. Blood samples were assayed for cortisol and MCPP levels every 30 min. The PD group had an augmented cortisol release when compared to the other two groups. Finally, a significant correlation was found across all subjects between clinical anxiety level and cortisol release on MCPP. These data support the hypothesis of 5HT receptor hypersensitivity in PD. PMID- 2906154 TI - Role of dopamine D-1 and D-2 receptor subtypes in mediating dopamine agonist effects on food consumption in rats. AB - The effects of selective D-2 and D-1 dopamine (DA) receptor agonists on food consumption were investigated in free-feeding rats. A selective D-2 receptor agonist, (+)-4-propyl-9-hydroxynaphthoxazine (PHNO), increased the consumption of standard food pellets in the dose range of 7.5-120 micrograms/kg, while SKF 38393 (5.0 mg/kg), a selective D-1 receptor agonist, decreased food pellet intake. The increase in food pellet intake produced by PHNO was blocked by haloperidol (an antagonist relatively selective for the D-2 receptor at the dose used, 0.05 mg/kg) and SCH 23390 (20 micrograms/kg, a D-1 receptor selective antagonist). Increasing "arousal" by disturbance associated with repeated food weighing also increased food pellet consumption, but did not diminish PHNO-elicited feeding. However, the same range of doses of PHNO (7.5-120 micrograms/kg) which increased food pellet intake decreased consumption of a liquid diet, and had no overall effect on a highly palatable liquid diet. The increase in consumption of solid food induced by PHNO appears to be secondary to enhancement of chewing behaviors. In contrast, the decrease in food intake induced by SKF 39393 may be due to a direct action of the drug on neural feeding mechanisms. PMID- 2906155 TI - Acute barbiturate administration increases benzodiazepine receptor binding in vivo. AB - Barbiturates have been reported to augment benzodiazepine receptor affinity in vitro, but their effects in vivo are uncertain. We determined benzodiazepine receptor binding in vivo by specific uptake of [3H]Ro15-1788 after barbiturate administration. Pentobarbital (30 mg/kg) increased receptor binding in cerebral cortex and cerebellum at 30 min after injection, with a peak effect occurring at 1 h after dosage, and a return to control levels at 2 h. Specific binding was increased at 1 h after pentobarbital administration in a dose-dependent fashion (7.5-90 mg/kg). Pentobarbital at doses up to 30 mg/kg failed to alter nonspecific binding, but at doses of 60 mg/kg increases in nonspecific binding were observed. The increases in specific binding observed after barbiturate administration were most likely due to a change in apparent receptor affinity, as determined by administration of varying doses of clonazepam to pentobarbital-treated (30 mg/kg) animals. The order of potency of a series of barbiturates in augmenting benzodiazepine receptor binding in cerebral cortex and cerebellum in vivo was: secobarbital greater than pentobarbital greater than amobarbital greater than phenobarbital greater than barbital. The same relative rank order of potency exists for the anesthetic/hypnotic activity of these barbiturates. These data suggest that barbiturates increase the apparent affinity of benzodiazepine receptors in vivo; unlike their in vitro actions, these alterations can be detected with a receptor antagonist. PMID- 2906156 TI - Influence of alpha stimulants and beta blockers on yohimbine toxicity. AB - 1. Potentiation of yohimbine-induced sublethality has been largely used to predict antidepressant action. 2. Several products were tested in order to understand the mechanism of this toxicity better: an alpha-1 central stimulant (adrafinil); an alpha-2 central stimulant (clonidine); and 4 beta-blockers (propranolol, atenolol, penbutolol and metoprolol). 3. It was found that atenolol and adrafinil could not antagonize toxicity, whereas clonidine and the other 3 beta-blockers could. 4. It is suggested that a central beta-origin toxicity exists since only beta-blockers which cross the blood-brain barrier are capable of antagonizing this activity. 5. The fact that clonidine also antagonized this toxicity may be explained by the beta-antagonist action of this substance at the high doses used. PMID- 2906157 TI - Successful treatment of idiopathic hypersomnia and narcolepsy with modafinil. AB - 1. Modafinil, a putative central alpha 1 adrenergic agonist, was tested in idiopathic hypersomnia and narcolepsy. 2. Sleep attacks and drowsiness were significantly decreased in 83% of 18 hypersomniac subjects and 71% of 24 narcoleptics. 3. When cataplectic episodes were not totally suppressed the association of a low dose of Clomipramine was successful in improving them. 4. Modafinil, used for at least 3 years in some patients, produces, in most cases, no peripheric sides effects, does not disturb night sleep and is never responsible of tolerance of drug dependence. PMID- 2906158 TI - Characterization of 3H-2-oxo-quazepam binding in the human brain. AB - 1. 2-oxo-quazepam (2oxoquaz) is a novel benzodiazepine (BZD) hypnotic containing a trifluoethyl substituent on the ring nitrogen at position 1, which, unlike other BZDs, distinguishes two populations of BZD binding sites. In the present study we characterized the binding of 3H-2oxoquaz to human brain membrane preparations. 2. Self and cross displacement curves for 3H-FNT and 3H-2oxoquaz binding in different brain areas indicate that 2oxoquaz binds with different affinities to two populations of binding sites in the human brain. 3. Competition studies of 3H-2oxoquaz (2 nM) and 3H-FNT (0.5 nM) binding with a series of unlabelled ligands indicate that compounds which preferentially bind to Type I sites are more potent at displacing 3H-2oxoquaz than 3H-FNT from cerebral cortex membrane preparations. 4. The binding of 3H-2oxoquaz is stimulated by gamma aminobutyric acid (GABA) and pentobarbital in a concentration-dependent manner. 5. The results suggest that in the human brain 3H-2oxoquaz binds with high affinity to a subpopulation of BZD recognition sites (Type I sites) which are functionally linked to the GABA receptor and the chloride ionophore. PMID- 2906159 TI - Phase 1 study of a new antipsychotic drug, OPC-4392. AB - 1. A phase I study of OPC-4392 (OPC), a quinolinone derivative recently developed in Japan and recognized to have an agonistic effect on dopamine autoreceptors, was performed in 7 male healthy volunteers in comparison with chlorpromazine (CPZ). 2. Clinical pharmacology The main clinical symptoms of OPC were sleepiness, weakness, fatigability, heavy headedness, disturbance of concentration, nausea, etc. The severity of these symptoms increased dose dependently, and the upper limit dosage of OPC was considered to be 5 mg for the healthy volunteers. 3. Endocrinological research The serum prolactin level decreased dose-dependently in the OPC group, whereas it rose in the CPZ group. A significant negative correlation was recognized between the OPC-plasma level and serum prolactin level as well. 4. Psychological tests In the Kraepelin test, a decrease in the average work quantity was observed in both groups, but it was less in the OPC group. 5. Pharmacokinetic study From the pharmacokinetic parameters measured, two features were recognized: one was the slowness of Tmax (4-6 hours) and the other was the length of its biological half-life (56-88 hours). It was estimated that the plasma level of OPC-4392 would take 2 weeks to reach a steady state. PMID- 2906160 TI - Treatment of tardive dyskinesia with ceruletide. AB - 1. Seven patients with TD were treated with a single dose of ceruletide 0.8 microgram/kg i.m. 2. EMG and MV were recorded, and the average power spectrum was computed. 3. Effect of ceruletide on TD within 2 hr after injection was varied (3 cases: inhibitory, 2 cases: facilitatory, 2 cases: no effect). 4. Two patients with severe TD, who showed improvement after a single administration, received repeated administration of ceruletide (0.6 microgram/kg i.m.) and their TD symptoms were recorded on videotape for blind consensus ratings. In both patients ceruletide caused a marked decrease in severity of TD, and the effects lasted for several weeks. 5. The present findings might contribute to further understanding of the role of CCK in the brain and to the treatment of TD. PMID- 2906162 TI - Cerebellar vermal size predicts drug response in schizophrenic patients: a magnetic resonance imaging (MRI) study. AB - 1. In schizophrenic patients, a good drug response was associated with a small cerebellar vermis brain ratio (CVBR). 2. It was possible to predict drug response with a higher statistical significance based on CVBR, especially in nonfamilial patients with schizophrenia. PMID- 2906161 TI - Serum neuroleptic activities required to inhibit relapse in schizophrenic patients--a study by radioreceptor assay. AB - 1. The serum levels of antidopaminergic (anti-D2), anti-alpha-adrenergic (anti NA) and antiserotonergic (anti-5HT2) activities of neuroleptics were determined in schizophrenic patients on maintenance treatment. 2. The patients whose conditions remained stable had significantly higher serum levels of anti-D2 and anti-5HT2 activities than those who were considered to be in unstable conditions after a period of remission. 3. However, the serum levels of anti-5HT2 activity in patients whose conditions remained stable varied as much as those of anti-NA activities did, so it appeared that from a pharmacological viewpoint anti-D2 activity of neuroleptics was the most important in preventing a relapse in schizophrenic patient. 4. The serum levels of anti-D2 activity required to prevent relapses differed for each neuroleptic. 5. The frequency of side effects increased concordant with increasing serum levels of anti-D2, anti-NA and anti 5HT2 activities, and unfortunately even minimum effective serum levels of anti-D2 activity elicited slight side effects in the majority patients. PMID- 2906163 TI - [Effect of carbimazole and dexamethasone on the TSH bond (TBII) inhibiting immunoglobulins in Graves-Basedow disease]. PMID- 2906164 TI - Effect of subinhibitory concentrations of tiamulin on the haemagglutinating properties of fimbriated Escherichia coli (K88, K99). AB - The haemagglutinating properties (HA) of Escherichia coli possessing the fimbrial antigens K88 and K99 were significantly affected by tiamulin. HA for K88-positive strains was reduced at 1/10 to 1/40 minimum inhibitory concentration (MIC), while the corresponding values for the K99 strains were 1/2 to 1/10 MIC. Tiamulin concentrations of 3 to 12 micrograms ml-1 increased salt aggregation test values from between 1.4 and 1.5, to more than 2. PMID- 2906165 TI - The effect of almitrine bismesylate on the steady-state responses of arterial chemoreceptors to CO2 and O2 in the cat. AB - The interaction between almitrine bismesylate, a pharmacological stimulant of peripheral chemoreceptors, and varying levels of oxygen (PO2 50-600 Torr) and carbon dioxide (PCO2 10-65 Torr) on steady state carotid chemoreceptor discharge was investigated in pentobarbitone-anaesthetised cats. Almitrine was given as constant intravenous (50 micrograms/kg per min for 4 min) and intracarotid infusions (4-16 micrograms/kg per min) at different levels of alveolar PO2 and PCO2. Almitrine always excited discharge. The intracarotid infusions at the lower infusion rate (4-8 micrograms/kg per min) and the i.v. infusions increased the slope of the isoxic response to CO2. This effect could be reversed by raising PO2 to high levels. Higher infusion rates of almitrine (16 micrograms/kg per min) displaced the CO2 response curve upwards but did not increase its slope above that obtained in control conditions at end-tidal PO2 of 50 Torr. However, as these higher infusion rates caused levels of discharge greater than those achieved during control conditions, their effects on control CO2 sensitivity could not be ascertained. Our results suggest that almitrine excites carotid body chemoreceptors by a mechanism similar to that of hypoxia and not like that of carbon dioxide. PMID- 2906167 TI - [Inflammatory arteritis of Takayasu's disease type and retroperitoneal fibrosis]. PMID- 2906166 TI - [Pneumopathies caused by salazosulfapyridine. A review of the literature apropos of a personal case]. PMID- 2906168 TI - [Takayasu arteritis with secondary hypertension in pregnancy]. PMID- 2906169 TI - Regulation of blood pressure by central neurotransmitters and neuropeptides. PMID- 2906170 TI - The roles of calcium and phosphoinositides in the mechanisms of alpha 1 adrenergic and other agonists. PMID- 2906172 TI - Entamoeba histolytica infection in a rehabilitation center for mentally retarded persons in Japan. PMID- 2906171 TI - Double-blind comparison of 3-day versus 7-day treatment with norfloxacin in symptomatic urinary tract infections. The Inter-Nordic Urinary Tract Infection Study Group. AB - The therapeutic efficacy and safety of norfloxacin 400 mg twice daily for 3 or 7 days was compared in a double-blind randomized multiclinic study including 485 female general practice patients with uncomplicated symptomatic lower urinary tract infections. 373 patients were considered valid for efficacy, 193 in the 3 day treatment group and 180 in the 7-day treatment group. The short-term efficacy (elimination of significant bacteriuria 3-13 days post-treatment) was 93.8% and 96.6% in the 3 and 7-day treatment groups, respectively, and the accumulated efficacy (elimination of significant bacteriuria 3 days post-treatment up until 45 days after the first dose) 81.3% and 91.7%, respectively (p less than 0.004). The median time to disappearance of symptoms was 3 days in both groups. Norfloxacin was well tolerated in both treatment groups. PMID- 2906173 TI - [Nitrate tolerance]. AB - Nitrate tolerance is defined as an attenuation or even loss of hemodynamic and anti-ischemic effects during continuous nitrate medication. The blunted response may be due to the development of pseudotolerance and true pharmacologic tolerance. Pseudotolerance is the result of volume and salt retention, as well as the stimulation of counter-regulatory mechanisms which may alter the baseline hemodynamics of a patient during nitrate therapy. Far less important are changes in nitrate pharmacokinetics. True pharmacological tolerance may also be of practical importance. Diminished uptake of nitrates into the vascular smooth muscle cell, a decrease in intracellular SH groups, inhibition of the guanylate cyclase, and stimulation of a specific phosphodiesterase may result in a decrease of cyclic GMP formation and hence to a decrease in nitrate induced vasodilatation. Tolerance development may be prevented by intermittent nitrate administration providing intervals with low plasma and tissue nitrate levels. In consequence, nitrates should be used predominantly for treatment of ischemic episodes, but 24-hour anti-ischemic action for the prevention of ischemia can be better achieved by treatment with a beta-blocker and/or a calcium antagonist. Nitrates should be added in times of maximum susceptibility to ischemia, while allowing nitrate levels to fall at other times. PMID- 2906174 TI - [Negative inotropic action of famotidine]. AB - In a randomized placebo-controlled study, 12 healthy volunteers were treated for one week each with nifedipine 10 mg four times daily or the same dose of nifedipine concurrently with famotidine 40 mg once daily per os. Famotidine did not significantly alter pharmacokinetic parameters of nifedipine. Determination of systolic time intervals showed that pre-ejection period (PEPc) and the ratio of pre-ejection period over left ventricular ejection time (PEP/LVET) were significantly reduced by administration of nifedipine plus placebo. Coadministration of famotidine and nifedipine, however, led to a significant increase in these parameters. Also, administration of famotidine alone to the same subjects led to a significant rise in PEPc and PEP/LVET. In impedance cardiography, stroke volume and cardiac output were significantly reduced by famotidine, whereas the H2-antagonist did not alter heart rate. This observation indicates for the first time that famotidine may exert negative effects on cardiac performance. In our opinion this could be of clinical relevance in elderly subjects or in patients with heart failure. PMID- 2906175 TI - [The role of alpha-adrenergic reception in bronchial asthma]. PMID- 2906177 TI - Transplacental teratogenesis and mutagenesis in mouse fetuses treated with cyclophosphamide. AB - We studied transplacental fetotoxicity, teratogenicity, and mutagenicity in Swiss Webster mice following different doses of cyclophosphamide (CP; 0, 5, 10, 15, or 20 mg/kg), a well-known mutagen/teratogen, on day 12 of gestation. The fetal survival and weight on day 18 of gestation decreased significantly with increasing CP dose (P less than 0.01). The CP-treated fetuses were also dysmorphic (e.g., shortened limbs, digital defects, cleft palate, open eyes, and hydrocephaly) and the percentage of dysmorphology increased with increasing CP doses (P less than 0.01). To evaluate mutagenesis, a separate group of females received 5-bromodeoxyuridine tablet (50-mg) implants on day 12 of gestation and a CP treatment 8 h later. Fetal liver cells were harvested 24 h post-BrdU implant to analyze sister chromatid exchange (SCE) frequency and micronuclei. CP caused a significant increase in the SCEs per fetal liver cell from 3.4 +/- 0.02 (control) to 90.0 +/- 0.04 (20 mg/kg CP) (P less than 0.01). The increasing CP dose was also related to an increase in micronuclei. The data suggest that CP is transplacentally toxic, teratogenic, and mutagenic. Further analyses of the data suggest that the mutagenic effects of CP may in fact contribute indirectly to the CP-related teratogenic effects. Such conclusions are based on path analysis with directional causations associated with SCEs per cell and the dysmorphic features studied. PMID- 2906176 TI - Effects of the antioxidant butylated hydroxytoluene (BHT) on retinal degeneration induced transplacentally by a single low dosage of N-methyl-N-nitrosourea (MNU). AB - A 1 mg/kg dose of the DNA alkylating agent, N-methyl-N-nitrosourea (MNU), when administered on day 16 of gestation provokes a progressive retinal degeneration in CD-1 albino mice reared under standard fluorescent lighting conditions (12 hr light: 12 hr dark); this degeneration begins at about 4 weeks post-natally and worsens with age. It is accelerated by constant fluorescent light exposure but is retarded greatly by constant darkness, suggesting the importance of secondary insults in the post-natal period for development of the degenerative disease. To determine whether the secondary photochemical damage might be specifically blocked, MNU-exposed and control animals in the present study were fed an antioxidant-enriched diet of Purina mouse chow supplemented with 0.75% butylated hydroxytoluene (BHT). A second group of MNU-exposed and control animals were fed a non-BHT supplemented standard Purina mouse chow diet. Systematic measurements of the number of rows of photoreceptor cell nuclei, the thickness of the inner/outer segment layer, and the thickness of the whole retina were made, to quantify and degenerative changes in animals 2, 4, 6, and 8 weeks of age. By 8 weeks, retinas of BHT-fed, MNU-exposed animals were significantly thicker and had more rows of photoreceptor cell nuclei than regular-diet, MNU-exposed animals. Moreover, the retinas of BHT-fed animals, both for MNU-exposed and controls, demonstrated sporadic morphologic changes in the form of circular configurations composed of ganglion cells, arcades of nuclear and plexiform layers, and, in one control animal, a hyperplastic nodule. These experiments suggested that MNU induced retinal degeneration may be retarded by a BHT-enriched diet; however, continuous high doses of this compound pre- and postnatally may induce other retinal abnormalities. PMID- 2906178 TI - Somatic mutation induced by heliotrine in Drosophila. AB - The pyrrolizidine alkaloid heliotrine has been shown to be a powerful mutagen in Drosophila. This report has evaluated the teratogenicity of heliotrine in this organism. The alkaloid was fed to larvae and its teratogenic effects measured in various developmental stages of the insect. The pupal stage is predominantly affected. The main consequences of treatment were failed eclosions at higher alkaloid concentrations (10(-4) M), while lower concentrations (10(-5) M) permitted the eclosion of adults, but these showed abdominal abnormalities ranging from severe distortions to reduced numbers of tergite bristles. mei-9 strains of Drosophila were more sensitive to the production of somatic chromosomal changes as well as the teratogenic effects of the alkaloid. These strains also showed reduced numbers of cells in histoblast nests of 6-hour-old prepupae. It is suggested that reduced numbers of histoblast cells in prepupae may be a consequence of genetic damage and this in turn leads to the abdominal distortions and reduced bristle numbers observed. PMID- 2906179 TI - Comparative antimutagenicity of chlorophyllin and five other agents against aflatoxin B1-induced reversion in Salmonella typhimurium strain TA98. AB - Chlorophyllin was studied for its antimutagenic activity against aflatoxin B1 in Salmonella typhimurium strain TA98 using the plate-incorporation test in the presence of S9 activation. Comparative antimutagenicity between chlorophyllin and certain commonly studied antimutagens (i.e., vitamins A, C, and E, retinoic acid, and beta-carotene) was also examined. A dose-related inhibition of aflatoxin B1 mutagenicity by chlorophyllin was observed, with the mutagenicity being abolished by 860 nmole chlorophyllin per plate. The inhibitory activity of chlorophyllin occurred only when cells were treated concurrently with chlorophyllin and aflatoxin B1. The antimutagenic potency of chlorophyllin was comparable to that of vitamin A and higher than that of retinoic acid and beta-carotene. Vitamins C and E had no effect on aflatoxin B1 mutagenicity under the conditions used. The results of toxicity tests and a reconstruction experiment showed that inhibition of the mutagenicity of aflatoxin B1 by chlorophyllin and the other active agents was due to antimutagenicity. PMID- 2906180 TI - Living in a chemical world: actions and reactions to industrial carcinogens. AB - The synthesis of chemical substances has resulted in technological benefits for society and has also caused increased chemical exposures and risks of related cancers. Although progress has been made in cancer treatment, there has been little improvement in real survival time for people who develop the major forms. Therefore, the need to prevent cancer is paramount. The greatest chemical exposures and risk of associated preventable cancers are found in the workplace, but generally environmental exposures receive greater public attention. Chemical causes of cancer have been identified, and in some cases decades have passed before controls have been adequately instituted. Some companies show a high regard for worker health, while others may minimize or misrepresent the hazards to exposed workers. Medical personnel receive relatively little education in the recognition of industrially related diseases. Workers are often unaware of their risks or are trapped in jobs because of economic necessity, and government has been slow to regulate, in part because of lobbying efforts. Experience has shown that when chemicals are regulated relatively soon after they are identified as hazardous, lives are saved, and the industry is economically healthy; however, when regulation is delayed, thousands of people die unnecessarily, and the cost to industry and society are phenomenal. Society has the opportunity to apply the knowledge learned from these experiences as we address current problems of chemical pollution. PMID- 2906181 TI - Platelet aggregation induced by equinatoxin. AB - Equinatoxin, isolated from Actinia equina, caused aggregation of washed rabbit platelets at a concentration as low as 0.01 ng/ml. ATP was released, but no formation of thromboxane B2 in challenged platelets. The aggregation was resistant to indomethacin or creatine phosphate/creatine phosphokinase or PAF antagonist. The aggregation was inhibited by imipramine, sodium nitroprusside, mepacrine, theophylline, prostaglandin E1 and EDTA. However, heparin and tetracaine were without any inhibitory effect. Verapamil suppressed both the aggregation and release reaction caused by equinatoxin in calcium concentrations from 0.01 to 15 mM. High concentrations of equinatoxin caused progressive cell lysis. It is concluded that equinatoxin-induced platelet aggregation is independent of ADP, thromboxane or PAF pathway. Phosphoinositide breakdown by phospholipase C is postulated to accomplish this phospholipase A2-independent platelet aggregation by equinatoxin. PMID- 2906183 TI - [Specialist information and knowledge of radiation protection according to the x ray ordinance for physicians and medical assistant personnel]. PMID- 2906182 TI - HLA class II genes polymorphism in DR4 giant cell arteritis patients. AB - We have previously reported a significant increase of HLA-DR4 antigen frequency in giant cell arteritis (GCA). This finding suggested an important role of immunogenetic factors in this syndrome. Recent data suggest that inherited susceptibility to several autoimmune diseases was associated with specific DR4 associated DQ beta alleles. DNAs from 27 DR4 positive patients with GCA were digested with Taq I and Bam HI, analysed on 0.7% agarose gel and hybridized with DR beta, DQ alpha and DQ beta probes. DR beta hybridization produced no variant detectable within DR4. DQ beta probe confirmed two clusters among DR4 associated DQW3 alleles: DQW 3.1 (Bam HI 360 Kb) and DQw 3.2 (Taq I 1.9 Kb and Bam HI 11 Kb). Among our 27 DR4 positive patients, 34% were DQW 3.1 and 66% were DQW 3.2. These frequencies are the same as those observed in healthy controls. PMID- 2906184 TI - Sulphasalazine and new related compounds. PMID- 2906185 TI - [Current value of gamma-glutamyltransferase levels]. PMID- 2906186 TI - [The first experience with crural plastic surgery using island composite skin flaps]. AB - An analysis of literature data, topographo-anatomical studies of 23 lower extremities and an experience with using 18 island fasciocutaneous flaps of the lower leg are presented. The article describes the possibilities of using a new donor area for plasty of limited defects of the lower leg and foot after various traumas and their sequelae. PMID- 2906187 TI - EHS nephropathy. A long-term morphological and immunohistochemical study. AB - Rats immunized with an emulsion of Engelbreth-Holm-Swarm (EHS) tumour and Freund's complete adjuvant (FCA) excreted large amounts of urinary protein from the 14th week after the initial immunization. The amount of urinary protein increased progressively and, after 1 year, reached over 1 g/day. Kidneys removed from immunized rats at 10 weeks, 24 weeks and 1 year after the initial immunization were examined by immunofluorescence, light and electron microscopy. By immunofluorescence microscopy, granular deposits of rat immunoglobulins (Igs) were observed along the glomerular capillary walls from the 10th week until the end of the observation period. Glomerular membranous transformation was observed from the 24th week by light microscopy. The glomerular capillary walls were thickened and argyrophilic spikes and vacuolations were detected. At 1 year the severity of these changes was increased. Electron microscopic examination showed only a few electron-dense deposits after 10 weeks, but after 24 weeks numerous electron-dense deposits were detected in all glomeruli, the glomerular basement membrane was thickened and irregular and podocyte foot processes were effaced. At 1 year, dense deposits were located intramembranously and their density decreased from the circumference to the centre. Lesions characteristic of human membranous nephritis were observed in this model, the appearances at 10 weeks, 24 weeks and 1 year corresponding to stages I, II and III, respectively, of the classification of Ehrenreich and Churg (1968). Comparison of the immunohistochemical abnormalities in this model and in Heymann nephritis revealed antigenic cross reactivity; there appears to be common antigenicity between the immune deposits in the glomeruli in both models, cell surface antigens in the EHS tumour and those located in the cell surface antigens in the brush borders of proximal convoluted tubules. Although the antigens responsible have not yet been clearly identified, in this paper I describe a new model of membranous nephritis, tentatively termed EHS nephropathy. PMID- 2906188 TI - Immunohistochemical studies on the tissue localization of collagen types I, III, IV, V and VI in schwannomas. Correlation with ultrastructural features of the extracellular matrix. AB - The distinctive tissue localization of collagen types in typical schwannomas with Antoni type A and B areas was demonstrated immunohistochemically using affinity purified antibodies against types I, III, IV, V and VI collagen and comparative ultrastructural studies were made on the extracellular matrix components. Antoni type A tissue, which was composed of tightly packed spindle cells with long cytoplasmic processes surrounded by a continuous basement membrane and a few fibrillar components of the extracellular matrix, was almost exclusively immunoreactive for type IV collagen, presumably representing the basement membrane. Verocay bodies, which are organoid structures of Antoni type A tissue, had a variety of more abundant extracellular fibrous components, such as banded collagen fibrils, fibrous long-spacing fibrils and microfibrils. These were positive for type I and III, as well as type IV collagen. In Antoni type B areas, where two types to tumor cells designated Schwann cell-like and fibroblast-like were scattered in large amounts of amorphous extracellular matrix containing microfibrils and thick banded collagen fibrils, type VI collagen as well as types I, III and IV collagen were consistently detected. Type V collagen was localized in dense fibrous tissue areas and around blood vessels. These findings indicate that the differently organized cellular patterns of schwannomas, identified as Antoni types A and B, are characterized not only by the ultrastructural features of the extracellular matrix, but also by the distinctive collagen types produced by neoplastic Schwann cells. PMID- 2906189 TI - Renal oncocytoma. I. Cytochrome c oxidase in normal and neoplastic renal tissue as detected by immunohistochemistry--a valuable aid to distinguish oncocytomas from renal cell carcinomas. AB - Using a polyclonal antibody raised against bovine heart cytochrome c oxidase, the occurrence of this mitochondrial marker enzyme has been investigated in 63 kidney tumors (ten renal oncocytomas, 43 renal cell carcinomas and ten tubulopapillary adenomas) as well as in normal renal tissue by an immunoperoxidase method (PAP technique). The differentiation between renal oncocytomas and mitochondria-rich carcinomas represents a problem of histopathology since these tumors have a different prognosis and require different patient managements. The strong immunoreactivity in renal oncocytomas contrasted with the much weaker reactivity in renal carcinomas and adenomas. Even mitochondria-rich (granular cell type) carcinomas exhibited only moderate staining intensity. Furthermore, single strongly stained oncocytes or small complexes were sometimes detected in normal renal tissue. The demonstration of marked differences in enzyme content between renal oncocytomas and granular cell carcinomas renders this method suitable for unequivocal distinction between these renal neoplasms. The antibody proved to be a valuable marker for detecting "true" oncocytic transformation in renal tumors and was useful in defining even single oncocytes or small oncocytic lesions. PMID- 2906190 TI - The distribution of endocrine cells along the mouse intestine: a quantitative immunocytochemical study. AB - The topographical distribution of endocrine cells in the crypt and villus epithelium along the length of the mouse intestine was studied. Argyrophil reactivity using the Grimelius stain was used to estimate the total endocrine population of the intestine. Comparisons were then made with the fraction of endocrine cells containing glucagon like material, stained immunocytochemically using rabbit anti-glucagon antisera. A highly significant reduction in the incidence of endocrine cells (argyrophil reactive) from the proximal to distal end of the intestine was noted. However, only 10-30% of these cells contained glucagon like material in the crypts of the duodenum, jejunum and ileum, compared to 30-60% in the crypts of the colon and rectum. The distribution of endocrine cells (argyrophil reactive) was maximal in the lower regions of the proliferative zone of the crypts but showed no significant variation along the length of the villi. Cells containing glucagon like material were also most frequent in the lower regions of the proliferative zone of the crypts, but were not generally found above the bottom third of the villi. Each crypt in the small intestine contains between 3 and 5 endocrine cells one of which contained glucagon like immunoreactive material. In the colon and rectum each crypt contains about 6-8 endocrine cells, of which 3-4 contained glucagon like immunoreactive material. These results indicate that a sub-set of cells containing glucagon like material, differentiate early in the lineage of endocrine cells within the proliferative zone of the intestinal crypts. PMID- 2906191 TI - Unusual mitochondrial reaction in psoriatic keratinocytes. AB - Electron microscopic investigation of skin biopsies revealed that keratinocytes in clinically uninvolved skin from psoriatic patients show the same mitochondrial ring phenomenon after the application of dithranol as has been observed in the cutaneous lesions proper. In various other skin diseases no mitochondrial reaction was evident after dithranol treatment, nor was it seen in chronic dermatitis when dithranol was not applied. It appears, therefore, that this morphological phenomenon is specific to psoriasis and may provide information concerning functional alterations in the pathogenesis of this disease. PMID- 2906192 TI - Disordered development of macrophages in non-Hodgkin's lymphoma. AB - Macrophage development in 20 untreated patients with non-Hodgkin's lymphoma (NHL) has been studied and compared with that in 20 normal subjects. Morphometric measurements were carried out on ultrastructural features of cell, nucleus and mitochondria during 6 days suspension culture of blood monocytes in the presence of autologous serum and lymphocytes. The results were subjected to multivariate and univariate analysis of variance. Statistically significant differences were found between the subject groups with respect to the volumes and surface areas of cell, nucleus and mitochondria, to the excess surface membrane of cell and nucleus (as compared with equivalent spheres) and to the number of mitochondrial profiles per section. It would appear that the patients' cell grew less, showed less elaboration of surface features and had reduced nuclear and mitochondrial development, the latter affecting mitochondrial numbers rather than individual size. The findings provide further evidence that mononuclear phagocytes are deranged in NHL. PMID- 2906193 TI - [Drug therapy of migraine]. AB - Out of the knowledge of various headache syndromes the physician has to develop a clear diagnostical and therapeutical concept. This is especially true for migraine. Relevant pathophysiological hypotheses are presented e.g. the neurogenic-vascular model of migraine. Metoclopramide and domperidone in combination with mono-analgesics, ergotamine and nonsteroidal-antiinflammatory drugs are favoured in the treatment of the acute migraine attack. 2 to 4 mg ergotamine for the attack, respectively 16 to 20 mg per month should not be exceeded. Mixed compounds, containing ergots, analgesics, codeine, caffeine, tranquilizers and barbiturates should be avoided as these drugs may induce rebound-headache. A prophylaxis of migraine is indicated if a migraineur suffers from at least 2 attacks per month or if a migraine attack lasts longer than 4 days. In the first place, beta-blockers and flunarizine, in some cases verapamil or naproxen, should be used; the effect of dihydroergotamine is questionable. Because of its severe side effects, methysergide should only be given if all other prophylactic drugs fail. Naproxen is standard medication in the short time prophylaxis of menstrual migraine. PMID- 2906194 TI - [Bikarfen--a new Soviet antihistaminic and antiserotonin preparation in the therapy of allergic dermatoses]. PMID- 2906195 TI - [The significance of multiple neuromediator activity in supporting integrative brain functions]. AB - Properties were studied of reactions of neural cells of the sensorimotor cortical area to locally microionophoretically administered l-glutamate, acetylcholine, norepinephrine and gamma-aminobutyric acid. It is shown that neuronal reactions to the action of the above-mentioned transmitters differ both in direction of change in the impulse activity frequency and in temporal offracteristics (latency and duration of after-effect). It is substantiated that due to the specificity of temporal ranges of action of the transmitter on neural cells, the possibility of effective interaction and temporal coding of heterofunctional information is provided. PMID- 2906196 TI - [Importance of venous anastomosis in autotransplantation of the testis]. AB - In the case of autotransplantation of an intraabdominal testis the venous anastomosis should performed in order to reduce the atrophy rate after testicular transplantation. PMID- 2906197 TI - Investigations on the opsonin-dependent interaction of Klebsiella bacteria and human polymorphonuclear leukocytes. AB - Encapsulated and nonencapsulated Klebsiella strains with different types of fimbriation were tested for their opsonin-dependent stimulation of human polymorphonuclear leukocytes (PMNs). Chemiluminescence (CL) of the PMNs was determined since CL-response can be used indirectly to quantitate phagocytosis. Apparently, the interaction between Klebsiella bacteria and human PMNs is dependent on the type of fimbration and on the presence of capsules. Evaluation of the bactericidal capacity of human PMNs against Klebsiella bacteria positively correlated with the chemiluminescence response demonstrating the importance of fimbriation and capsulation for this process, too. PMID- 2906198 TI - Dibromochloropropane (DBCP) effects on the reproductive function of the adult male rat. AB - In order to evaluate the effect of dipromochloropropane (DBCP) on reproductive function, groups of male adult Wistar rats were injected subcutaneously with different doses of DBCP. A strictly dose-dependent effect resulting in histological alteration principally toward the seminiferous tubules was observed. Sperm count and sperm motility showed azoospermia or oligoasthenospermia with a significative recovery in the lower dose of DBCP treated rats. Among the enzymatic activities evaluated as biochemical markers of testicular function: LDH was not appreciably affected by the DBCP treatment while GGT and NADPH-cyt P450 reductase significantly enhanced suggesting an induction of the detoxification processes. PMID- 2906199 TI - Calcium accumulation by glutamate receptor activation is involved in hippocampal cell damage after ischemia. AB - Rats exposed to 10 min of complete cerebral ischemia develop necrosis of the CA-1 region of the hippocampus after 2-3 days. We studied the involvement of synaptic transmission for this process by ablation of the afferent input (which is mainly glutamatergic) to CA1 by bilateral destruction of CA-3 neurons (Schafferotomi). The deafferentiation completely prevented the ischemic nerve cell destruction as revealed by histological studies after 6 days. The role of intracellular Ca++ overload was assessed by measurement of the interstitial Ca++ concentration. In control animals the interstitial Ca++ concentration decreases abruptly to 10% of the initial value 1.6 min after the onset of ischemia. The denervated hippocampi, however, showed no decrease during the 10 min of ischemia and hippocampi injected with 2-amino-5-phosphovalerate (APV), a competitive antagonist of the glutamate N methyl-D-aspartate (NMDA) receptors, displayed a significantly reduced decrease (45% of the initial value) during ischemia. It is concluded that calcium influx via the glutamate-operated channels during the ischemic period is an important link in the development of ischemic brain cell damage. PMID- 2906200 TI - Analysis of activation markers on tonsillar T lymphocytes. AB - Tonsillar T lymphocytes have several characteristics of activated lymphocytes, but the activation antigens are not detected on their surface, except for the Tac antigens by means of a sensitive protein A rosette assay. In this study the increased ability of tonsillar T lymphocyte to form autologous rosettes is presented. These data are in agreement with the hypothesis that tonsillar T lymphocytes contain activated T lymphocytes. PMID- 2906201 TI - RFLPs of 21-hydroxylase and C4 genes: application to pedigree analysis on 21 hydroxylase deficiency. PMID- 2906203 TI - Clinical forms of congenital adrenal hyperplasia: restriction length polypmorphism patterns in the CYP21 gene. PMID- 2906202 TI - Clinical applications of measuring thyroid receptor antibodies, thyroid stimulating and thyroid stimulation-blocking antibodies. PMID- 2906204 TI - [Application of aqueous Eudragit dispersions to the preparation of controlled release oral antihistamine dosage forms]. PMID- 2906205 TI - Determinants of the analgesic action of opiates. AB - Nociceptive reactivity (tail-withdrawal reflex at 60 degrees C) during morphine administration was investigated in rats of the same population but of different batches in animals during restraint stress after their housing under different environmental conditions. The variability of the analgesic effects of opiates strongly depended on the functional state of animals at the moment of morphine administration, on the aversion to the living conditions prior to morphine and on some individual peculiarities of the organism with regard to the adaptive changes in opiate receptors. The direct action of naloxone, administered periodically, on opiate receptors induced an enhancement of the analgesic effects of morphine, which might result from the compensatory supersensitivity of opiate receptors after their blocking. PMID- 2906206 TI - Effects of chronic diazepam and medazepam treatment on the level of biogenic monoamines in different rat brain areas. AB - Studies were made of the effect of 19-day administration of diazepam (1 mg.kg-1, i.p.) and medazepam (5 mg.kg-1, i.p.) on the level of biogenic monoamines in different rat brain areas: cerebral cortex, striatum, hippocampus, and hypothalamus. The noradrenaline (NA), dopamine (DA) and serotonin (5-HT) levels were determined. After chronic treatment with diazepam no alterations in the NA content in the cortex, striatum and hypothalamus were found. Medazepam increased the NA level in the cortex, striatum, and hippocampus without changing it in the hypothalamus. Repeated administration of diazepam or medazepam led to an increase in the DA level in the striatum. Both benzodiazepines provoked a significant increase in the hippocampal 5-HT level, which could be attributed to the antianxiety effect of these drugs. PMID- 2906207 TI - Participation of cholinergic mechanisms in the realization of the effect of bombesin on the migrating myoelectrical complex. AB - The experiments were carried out on dogs with chronically implanted bipolar ball shaped silver electrodes in the antral part of the stomach and duodenum. The effect of bombesin (injected intravenously in a dose of 200 ng/kg) on the migrating myoelectrical complex (MMC) was examined after pretreatment with hexamethonium (10 mg/kg) or atropin (100 micrograms/kg), or alpha-antagonists (phentolamine, 2 mg/kg) and beta-antagonists (propranolol, 2 mg/kg) of the adrenergic receptors. Introduced during the second MMC phase, bombesin caused inhibition of the spike activity, accompanied by an increase of the slow potential frequency. Prolonged intensified spike activity occurred 5-10 min later. Early brief appearance of spike potentials was observed after bombesin in the presence of hexamethonium, which was not manifested on the background of atropin. After hexamethonium or atropin, however, the phase of the late activation of the spike activity did not occur and there was no change in the effect of bombesin on the frequency of the slow potential. The alpha- and beta antagonists of the adrenergic receptors do not change the effect of bombesin on the electrical activity of the stomach and the intestines. PMID- 2906208 TI - Beta-adrenoblocking activity of a new derivative of 2-aminotetraline based on some metabolic responses in cats and rats. AB - Previous pharmacological investigations of a newly synthetized derivative of 2 aminotetraline: trans-2-isopropylamino-3-hydroxy-5,8-dimethoxy 1,2,3,4 tetrahydronaphthalene (3b) have shown it to possess a beta-adrenergic blocking activity. In the present work we studied the influence of 3b on some biochemical indices characteristic of beta-adrenergic stimulation: blood levels of glucose, lactate and FFA in cats and rats, and phosphorylase "a" activity in rat myocardium. The dose used (0.5 mg/kg) in rats was the same as the dose of propranolol (0.5 mg/kg). In all experiments on cats and rats compound 3b decreased the effects of isoproterenol on the blood levels of glucose, lactate and FFA and on the phosphorylase "a" activity of the myocardium and this action was comparable with that of propranolol. The similar molecular mass and LD50 of 3b and propranolol allowed quantitative comparisons of the beta-adrenoblocking effects of both drugs in the dose used. The results suggest that compound 3b possesses metabolic effects characteristic of beta-adrenoblocking agents. PMID- 2906209 TI - Gastrointestinal regulatory peptides during oxytocin infusion in post-term pregnancies. AB - The plasma concentrations of the gastrointestinal regulatory peptides vasoactive intestinal polypeptide (VIP), insulin, secretin, somatostatin, motilin, pancreatic polypeptide (PP) and gastric inhibitory polypeptide (GIP), as well as blood glucose, were measured in eight healthy women before, during and after oxytocin infusion in post-term pregnancies. Plasma VIP increased significantly (P less than 0.01) during oxytocin infusion. Plasma secretin showed a significant (P less than 0.05) decrease during oxytocin infusion. Plasma somatostatin remained unchanged during oxytocin infusion, but thereafter a significant (P less than 0.05) increase occurred. Both plasma motilin and plasma PP showed a non significant increase during oxytocin infusion with sustained levels thereafter. No changes were found for plasma insulin, GIP and blood glucose. PMID- 2906210 TI - Possible involvement of neuropeptide Y in sympathetic vascular control of canine skeletal muscle. AB - Sympathetic nerve stimulation (2 min, 2 and 10 Hz) increased perfusion pressure in the blood perfused canine gracilis muscle in situ after pretreatment with atropine, desipramine and beta-adrenoceptor antagonists. This vasoconstriction was accompanied by clear-cut increases in the overflow of endogenous noradrenaline (NA) at both frequencies and, at 10 Hz but not at 2 Hz, also of neuropeptide Y-like immunoreactivity (NPY-LI). The irreversible alpha adrenoceptor antagonist phenoxybenzamine enhanced the nerve stimulation induced overflows of NA and NPY-LI five- to eightfold and threefold, respectively. The fractional overflows of NA and NPY-LI per nerve impulse were similar in response to the high-frequency stimulation, indicating equimolar release in relation to the tissue contents of the respective neurotransmitter. The maximal vasoconstrictor response elicited by 10 Hz was reduced by about 50% following a dose of phenoxybenzamine which abolished the effect of exogenous NA and the remaining response was more long-lasting. Local i.a. infusion of NPY evoked long lasting vasoconstriction in the presence of phenoxybenzamine, while the stable adenosine 5(1)-triphosphate (ATP) analogue alpha-beta-methylene ATP was without vascular effects. Locally infused NPY reduced the nerve stimulation evoked NA overflow by 31% (P less than 0.01) at 1 microM in arterial plasma, suggesting prejunctional inhibition of NA release. In conclusion, NPY-LI is released from the canine gracilis muscle upon sympathetic nerve stimulation at high frequencies. There is nerve stimulation evoked vasoconstriction, which is resistant to alpha-adrenoceptor blockade. This may in part be mediated by NPY released together with NA from the sympathetic vascular nerves. PMID- 2906211 TI - Differential vasomotor action of noradrenaline, serotonin, and histamine in isolated basilar artery from rat and guinea-pig. AB - Vasomotor effects of the amines, serotonin (5-hydroxytryptamine; 5-HT), noradrenaline (NA) and histamine, were studied in isolated basilar arteries (BA) of the rat and guinea-pig in vitro. 5-HT produced marked contraction in rat BA, about 70% of that induced by high (124 mM) K+ solution. This response was inhibited by the specific 5-HT2 receptor antagonist, ketanserin, with a pA2 value of 9.35. In the guinea-pig, 5-HT caused only moderate contraction amounting to 30% of that produced by K+. Ketanserin at concentrations up to 10(-6) M showed a comparatively small, non-surmountable inhibition of the contraction. EC50 values for 5-HT in the guinea-pig and rat were 5.65 x 10(-8) M and 3.70 x 10(-7) M, respectively. NA had no effect on rat BA, but moderately contracted guinea-pig BA. The contraction was not altered by yohimbine but was inhibited by prazosin. Histamine contracted guinea-pig BA with a maximum that was 110% of the K+-induced contraction. It was not changed by the H2 antagonist, cimetidine. The H1 antagonist, pyrilamine, caused competitive inhibition with a pA2 of 9.20 at a slope of 0.94. In preconstricted rat BA, histamine induced vasodilatation in a concentration-dependent manner. The H1 agonist, pyridylethylamine (PEA), and the H2 agonist, impromidine, dilated less effectively than histamine. The vasodilatation induced by histamine was inhibited by the H2 antagonist, cimetidine, and to a smaller extent by the H1-receptor antagonist, pyrilamine. Removal of the endothelium abolished the vasodilator effect of PEA but not that of impromidine. In vessels with intact endothelium, the vasodilatation caused by histamine was slightly reversed by pyrilamine, which did not affect the dilatation in endothelium denuded vessels. Cimetidine markedly reversed this vasodilator effect in both intact and endothelium denuded preparations; in the latter the counteraction was almost complete. In precontracted guinea-pig vessels, histamine failed to induce dilatation even in the presence of the H1 antagonist, pyrilamine. Thus, 5-HT-induced contraction is mediated by 5-HT2 receptors in the rat and probably by 5-HT1 receptors in the guinea pig. NA failed to contract rat BA but contracted guinea-pig BA through alpha 1 receptors. Histamine was a potent dilator agent in rat BA through a combination of both H1 and H2 receptors. The dilatation mediated by the H1 receptors, but not that mediated by H2 receptors, was endothelium-dependent. Histamine caused strong vasoconstriction in the guinea-pig BA through H1 receptors. PMID- 2906212 TI - [Patient non-compliance with medication]. AB - Many psychiatric treatments are bound to failure when patients do not comply with the psychopharmacological schedule they were given, a situation which--quite frequently--obliges to forceful drug treatment or institutionalization. This paper attempts at displaying a range of strategies to be resorted to, so that patients are eventually persuaded to, literally, take their medicines as prescribed--provided the professional accepts patients own perspectives on their situation. In other words, he or she must start internalizing patients' symbolic codes, to be in a position of translating his or her concepts to patients, thus enhancing communication. Firstly, patients' primary need has to be definitely outlined. Then, the professional will find it easier to explain how the drug is going to help. The author proposes some ideas salespersons resort to when customer's persuasion is at stake, since he understands these ideas are likely to maximize psychiatrists' persuasive ability. PMID- 2906213 TI - Neurotransmitters, receptors and neuropeptides in post-mortem brains of chronic schizophrenic patients. AB - In the analysis of post-mortem brains of 14 chronic schizophrenic patients and 10 controls, biochemical evidence of a hyperdopaminergic state was found in the basal ganglia of schizophrenics; tyrosine hydroxylase activity was increased with a concomitant increase of homovanillic acid. Unusually high tyrosine hydroxylase activity was noted in 2 schizophrenic cases. The Bmax value of 3H-spiperone binding for schizophrenics was higher than the controls. We also found increased specific binding of 3H-kainic acid to the prefrontal cortex in schizophrenics. A negative correlation existed between 3H-kainic acid binding in the medial frontal cortex, and glutamic acid content in various brain areas. Increased immunoreactivity of substance P was found in more than ten brain areas. Methionine-enkephalin was also increased in three areas of the prefrontal cortex of schizophrenics. These results suggest that the hyperdopaminergic state co existed with glutamatergic hypofunction and increased neuropeptides in various brain areas of chronic schizophrenic patients. PMID- 2906214 TI - Brain and CSF somatostatin concentrations in patients with psychiatric or neurological illness. An overview. AB - Somatostatin was originally isolated as a 14-amino-acid peptide from the ovine hypothalamus. The peptide has a widespread regional distribution within the central and peripheral nervous systems, as well as in peripheral organs. Preservation of the chemical structure over a wide range of vertebral species indicates important functional roles of the peptide. Recent results about the role of somatostatin and related peptides in different psychiatric (depression, schizophrenia, Alzheimer's disease) and neurological (Huntington's disease, multiple sclerosis, Parkinson's disease) diseases, and the effects on the hypothalamic-pituitary-adrenal axis are summarized. Also, the influence of some psychotropic drugs (halo-peridol, carbamazepine) on somatostatin levels in cerebrospinal fluid is discussed. PMID- 2906215 TI - Why low-dose benzodiazepine-dependent insomniacs can't escape their sleeping pills. AB - Psychobiological aspects of low-dose benzodiazepine dependence (LBD) and drug withdrawal were investigated in 76 middle-aged and elderly chronic insomniacs in a sleep laboratory. Comparison with drug-free insomniacs showed that LBD leads to a complete loss of hypnotic activity and substantial suppression of delta and REM sleep. Only small differences were found between benzodiazepines with different half-life time. Upon withdrawal, recovery from this suppression, especially in REM sleep, occurred, while insomnia did not increase. The patients, however, reported sleeping longer while taking the drug compared with withdrawal. This misperception seems to be a specific effect of benzodiazepines, and contrasts with the full awareness of insomnia upon withdrawal. It is concluded that these effects play a leading role in the patients' inability to escape their sleeping pills. The response of REM sleep to withdrawal should make this a useful measure to objectively confirm low-dose benzodiazepine dependence. PMID- 2906217 TI - Transforming growth factor beta. PMID- 2906216 TI - Baseline studies on transmitter substances in cerebrospinal fluid in depression. PMID- 2906218 TI - A human major histocompatibility complex (MHC) DNA probe recognizes goat genes. PMID- 2906219 TI - Preparation of Hybridomas producing monoclonal antibodies against human interferon. AB - To prepare hybridomas secreting monoclonal antibodies (MoAb) against human alpha interferon (alpha-IFN), BALB/c mice were immunized with IFN produced in Namalwa cells. Native alpha-IFN, as well as partially purified or on cellulose adsorbed alpha-IFN preparations were used for immunization. Seven hybridomas continuously secreting IgG against human alpha-IFN were prepared by fusion of splenocytes from immunized donors with the mouse myeloma cells. MoAb reacted in ELISA as well as in neutralization test with human lymphoblastoid, leukocytic and recombinant alpha-IFN. PMID- 2906220 TI - Effect of cellular inhibitors on the infection of various susceptible cells with vesicular stomatitis virus. AB - The effect of some cellular function inhibitors on adsorption and successive events of penetration of vesicular stomatitis virus to phylogenetically unrelated permissive cells was investigated. Treatment of HeLa, CER, EPC and Aedes albopictus cells with colcemide and cytochalasin D which affect cytoskeleton organization indicated that microfilaments but not microtubules were involved in the early events of VSV infection. Inhibitors of oxidative phosphorylation such as dinitrophenol and sodium azide, and the glycolysis inhibitor 2-deoxy-D glucose, did not allow multiplication of prebound virions, demonstrating that VSV replication is largely energy dependent in either host cells examined. PMID- 2906221 TI - Clinico-immunologic and allergologic studies with the inactivated influenza virus vaccine purified and concentrated by gradient centrifugation. AB - Vaccination activity and safety of inactivated influenza centrifugal divaccine have been studied in groups of subjects aged 18 to 22, 15 to 16, and 9 to 14 years. The vaccine tested contained either a standard dose (6-8 micrograms) or double a dose (12-16 micrograms) of the haemagglutinin (HA) of influenza viruses A(H1N1) and A(H3N2). The double antigenic load of the vaccine did not enhance its reactogenicity for adults or adolescents aged 15 to 16 years. It enhanced, however, the production of antihaemagglutinine antibodies to the vaccine strains. The range of the antibodies formed and their persistence were independent on the virus dose. The increased dose (12-16 micrograms) of HA decreased the humoral immune response in school children aged from 11 to 14 years. Neither standard nor double dose of the vaccine caused any changes in the biochemical or haematological parameters of blood and urine. No allergic response was registered by the indirect mast cell degranulation (IMCD) test in rats. PMID- 2906222 TI - Contribution to laboratory diagnosis of mumps and parainfluenza. AB - Specific IgM and IgG antibodies to mumps virus (MV) were detected in sera of mumps-patients by ELISA in agreement with the results obtained by indirect immunofluorescence (IF). Of given sera 37.5% contained IgM reacting in indirect ELISA also with the antigens of parainfluenza virus (PiV) T3. In all patients with respiratory illness over 2 years of age, the significant increase of antibodies to PiV in haemagglutination inhibition (HI) test was in good correlation with serum IgM and IgG antibody levels to PiV T3 determined by ELISA; but, in addition, 30.7% of these sera cross-reacted with MV antigens. The cross reactions were eliminated by using MV-nucleocapsid antigen in indirect ELISA, or in direct ELISA using the peroxidase-labelled whole virion antigen. In some children under two years of age a discrepancy was observed between the significant increase of serum antibodies in HI and the inability to detect specific IgM antibodies by means of ELISA in their sera. The low-avidity antibodies appearing after primary PiV infection were probably washed off during the ELISA procedure. PMID- 2906223 TI - Action of epsilon-aminocaproic acid on the proteolysis system during experimental influenza in mice. AB - Proteolysis system was examined in influenza-virus-infected mice after a 5-day course of therapeutic or preventive treatments with the proteolysis inhibitor epsilon-aminocaproic acid (E-ACA). The mice were infected with nonadapted influenza virus A/Hong Kong/1/68 (H3N2). E-ACA was shown to exert a pathogenetic action expressed by a marked tendency to normalization of elevated alkaline protease activity in damaged lung tissue and in the blood of infected animals. E ACA induced a long-lasting high level activity of acidic proteases in the blood which correlated with increased protection of animals against influenza virus infection. It may be suggested that acidic proteases are involved in the preventive action of E-ACA and are a factor of resistance to virus infection. PMID- 2906224 TI - Structural basis for antiviral activity of flavonoids-naturally occurring compounds. AB - The effect of different substituents of quercetin and luteolin on the ability to inhibit the herpes simplex virus (HSV-1) replication in RK-13 cells was studied. It seems that parent compounds with free hydroxyl groups at C-5, C-7, C-3', C-4' and additionally at C-3 have the highest activity. Substitution of those groups caused decrease of or completely abolished the antiviral activity of the tested compounds. PMID- 2906225 TI - Probable metachromatic leukodystrophy/pseudodeficiency compound heterozygote at the arylsulfatase A locus with neurological and psychiatric symptomatology. AB - Metachromatic leukodystrophy (MLD) is an autosomal recessive progressive demyelination disorder caused by the deficiency of arylsulfatase A (ASA). However, there exist individuals with low ASA activity without clinical symptoms. This state is described as ASA pseudodeficiency (PD). A number of patients with low ASA activity and various neuropsychiatric symptoms have been observed. It is controversial to what extent low ASA activity predisposes for neurological and/or psychiatric symptomatology. Therefore, persons with low ASA activity who were collected from a large-scale screening among neuropsychiatric patients and healthy controls are presently being extensively evaluated using biochemical, genetic, and clinical methods. Here we present a female patient, who had been first hospitalized with the diagnosis encephalomyelitis disseminata. Her ASA activity determined in fibroblast extracts is intermediate between adult MLD and PD. Sulfatide degradation in cultured fibroblasts is diminished. The subunit pattern obtained after SDS-polyacrylamide gel electrophoresis and immunoblotting was determined in the index patient and 2 sibs. It is compatible with a compound genotype ASA-/ASAp in the index case. It appears probable that in this patient low ASA activity leads to the accumulation of sulfatide and either causes the appearance of neuropsychiatric symptoms or at least contributes to the demyelination process. PMID- 2906226 TI - Congenital adrenal hypoplasia and selective absence of pituitary luteinizing hormone: a new autosomal recessive syndrome. AB - Congenital hypoplasia of the adrenal glands (CHA) is a rare condition, particularly in the absence of a central nervous system (CNS) anomaly. Two major types of CHA have been described in the setting of an apparently normal CNS and pituitary: a cytomegalic type usually with X-linked recessive inheritance and a miniature adult type that, when hereditary, is an autosomal recessive trait. Glycerol kinase deficiency (GKD) is an X-linked recessive trait, and it may be associated with CHA and adrenal insufficiency, presumably because of deletion of adjacent X-linked loci. We report on three sibling infants, one male and two females, with normal CNS and lethal CHA of the miniature adult type, selective absence of pituitary LH; two of the infants also had glycerol kinase (GK) activity that was decreased but not in the GKD range. Restriction fragment length polymorphism (RFLP) analysis of X chromosome markers located at Xp21-p22 was carried out on the maternal grandfather, both parents, two of three affected infants, and a living normal brother. The results excluded the X-linked type of this disorder associated with GKD in this family. Autosomal recessive inheritance is most likely. PMID- 2906227 TI - [Effect of controlled normovolemic hemodilution on the activity of neurohumoral adaptive reactions in patients after operations on the abdominal organs]. PMID- 2906228 TI - [Causes of death in systemic vasculitis of polyarteritis nodosa. Analysis of a series of 165 patients]. AB - The case histories of the 49 patients who died in a series of 165 patients admitted to the Medical Unit between 1958 and 1984 with polyarteritis nodosa (PAN) were reviewed. The causes of death of the 29 men and 20 women, mean age 51.44 +/- 7.4 years, were classified into 6 groups. Infection accounted for 26.5% (13/49) of deaths, the initial site of infection being pulmonary, complicated by septicaemia in 6 cases. Cardiovascular events were responsible for death in 24.4% (11/49): terminal cardiac failure (4 cases), myocardial infarction (1 case), ventricular tachycardia (1 case), stroke (1 case), pulmonary embolism (2 cases), fulminant hemoptysis (1 case). Gastrointestinal complications were the cause of death in 16.3% (8/49): ischemic necrosis (5 cases), acute pancreatitis (2 cases), oesophageal ulceration (1 case). Renal failure was observed in 10.2% (5/49), all occurring before 1972: acute renal failure (3 cases), chronic renal failure (2 cases). Cancer was the cause of death in 10.2% (5/49): primary bronchial carcinoma (2 cases), laryngeal carcinoma (1 case), carcinoma of the vulva (1 case), bone metastases (1 case). Finally, 14.2% (7/49) could not be classified in the preceding groups. Sudden death occurred in 3 patients, shock in 1 patient, multivisceral PAN in 2 patients and anaphylactic shock in 1 patient. Three of the 12 patients who had post-mortem studies had signs of progressive vasculitis. The results are compared with other reports in the literature and the pathogenic mechanisms are discussed. The infections and cardiovascular deaths occurred early or late and were not related to the state of the activity of the vasculitis. Immunosuppressive treatment seems to play an important role in their pathogenesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2906229 TI - [The chlorazepate test in anxiety-depressive states]. PMID- 2906230 TI - [Tissue effects of pulsed-dye laser lithotripsy. Experimental study on the ureter in dogs]. AB - The tissue effects of pulsed dye laser (Pulsolith) were studied in 10 dog ureters. The results show the absence of ureteric perforation or damage to adjacent organs by the laser irradiation. The only lesions observed were focal hyperplasia of the urothelium and chorion with extremely limited abrasions of the urothelium. The absence of tissue damage of the pulsed dye laser allows it to be used in human clinical practice. PMID- 2906231 TI - Restorative treatment of the extensively traumatized dentition. PMID- 2906232 TI - Endodontics following trauma. PMID- 2906233 TI - [Hemodynamic effects at rest and exertion of a new partial beta-agonist (cicloprolol) in moderated cardiac failure]. AB - The haemodynamic effects of cicloprolol, a new partial beta 1-adrenoceptor agonist, were investigated at rest and during exercise in 10 patients with moderate heart failure. At rest, cicloprolol (0.10 mg/kg i.v.) increased heart rate by 8 p. 100 (80.6 +/- 5.7 vs 74.7 +/- 11.9 beats/min; p less than 0.05), cardiac index by 17 p. 100 (3.74 +/- 0.57 vs 3.20 +/- 0.41 l/min/m2; p less than 0.001) and stroke index by 6 p. 100 (46.3 +/- 8.3 vs 43.7 +/- 8.8 ml/beat/m2; p less than 0.05). Left ventricular end-diastolic pressure was reduced by 35 p. 100 (9.9 +/- 5.0 vs 15.2 +/- 7.4 mmHg; p less than 0.01). There were no significant changes in aortic pressure. Systemic vascular resistance decreased by 15 p. 100 (1,030.8 +/- 234.6 vs 1,209.6 +/- 319.7 dynes.s.cm-5; p less than 0.01). During moderate exercise (114 +/- 13 watts) in supine position, cicloprolol induced a 10 p. 100 reduction of tachycardia (99.7 +/- 10.2 vs 112.2 +/- 16.5 beats/min; p less than 0.01), a 6 p. 100 decrease of mean aortic pressure (112.4 +/- 19.7 vs 119.5 +/- 19.2 mmHg; p less than 0.01) and an 8 p. 100 decrease of cardiac index (5.42 +/- 0.63 vs 5.88 +/- 0.75 l/min/m2; p less than 0.001). There were no significant changes in left ventricular filling pressure and stroke index. When data obtained at rest and during exercise were pooled, an inverse linear relationship (p less than 0.01) was found between heart rate before treatment with cicloprolol and cicloprolol-induced variations in heart rate and cardiac index.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2906234 TI - The ultrastructure of somatostatin-immunoreactive cell bodies, nerve fibers and terminals in the dorsal horn of rat spinal cord. AB - The distribution and ultrastructure of somatostatin-immunoreactive neurons, nerve fibers and axon terminals in the dorsal horn of rat thoracic spinal cord were studied by immunohistochemistry at both the light and electron microscopic levels. Somatostatin-immuno reactive neurons were predominantly observed in Rexed laminae I and II of the dorsal horn of spinal cord. Somatostatin-immunoreactive electron dense peroxidase material was concentrated in the Golgi apparatus and rough endoplasmic reticulum of the somatostatin-immunoreactive neurons, and was characteristically sparse in other regions of the cytoplasm. In the somatostatin immunoreactive fibers and terminals, immunoreactive electron dense material was concentrated in the microtubules and large synaptic vesicles. PMID- 2906235 TI - Exocytotic release of neurotransmitter substances from nerve endings in the taste buds of rat circumvallate papillae. AB - Exocytotic release of neurotransmitters from nerve endings was demonstrated ultrastructurally in the taste buds of rat circumvallate papillae by stimulation of high K+ and Ca2+ Ringer perfusion and application of tannic acid-Ringer incubation (TARI) method. Omega-shaped images of large cored vesicles and small clear vesicles, indicating exocytotic release of their contents, were found only in the non-synaptic sites. Occasionally exocytosis occurred at sites facing other nerve fibers. Many coated pits were also seen, which presumably represent membrane retrieval at a later stage of exocytosis. It is likely that the taste buds receive more than one type of innervation. PMID- 2906236 TI - [Drug analysis with polarographic methods. XXXII. Reasons for the anomalous current-voltage curves of quazepam [7-chloro-5-(2-fluoro-phenyl) -1,3-dihydro-1 (2,2,2-trifluoroethyl)-2H-1,4-benzodiazepine-2-thione]. PMID- 2906237 TI - [Antimycobacterial properties of antihistaminic compounds]. PMID- 2906238 TI - Modulation of the activity of hepatic gamma-glutamyl transpeptidase, adenosine triphosphatase, placental glutathione S-transferase and adenylate cyclase by acute administration of lead nitrate. AB - The effect of a single administration of lead nitrate on the activity of gamma glutamyltranspeptidase (gamma-GT), adenosine triphosphatase (ATPase), the placental form of glutathione S-transferase (GST-P) and adenylate cyclase (AC), four enzymes widely used as phenotypic markers for preneoplasia, was investigated in the liver of male Wistar rats. The results of the histochemical enzymatic staining indicated that an acute treatment with lead nitrate induces the activity of gamma-GT, mainly in the hepatocytes located around zone I of the liver acinus, with a maximum seen between 72-96 hours. On the other hand, the activity of ATPase was found to be severely inhibited at 2-3 days after treatment, as shown by a strong decrease in the staining of the bile canaliculi of zones II and III. Immunohistochemical analysis revealed that lead nitrate administration also resulted in the appearance in most of the hepatocytes of GST-P, an enzyme whose activity is almost undetectable in normal rat liver, but is elevated in preneoplastic liver lesions. Finally, lead nitrate treatment resulted in an inhibition of AC activity which was maximal after 24 hours. PMID- 2906239 TI - Identification of a surface membrane proton-translocating ATPase in promastigotes of the parasitic protozoan Leishmania donovani. AB - ATPase activities were measured in surface membranes and mitochondria isolated from promastigotes of the parasitic protozoan Leishmania donovani. The two enzymes were differentiated on the basis of pH optima, inhibitor sensitivity and by immunochemical methods. The surface-membrane (SM-) ATPase had an activity of 100 nmol/min per mg of protein, which was optimal at pH 6.5. The enzyme was Mg2+ dependent, partially inhibited by Ca2+, and unaffected by Na+ or K+. The SM ATPase was inhibited by orthovanadate, NN'-dicyclohexylcarbodi-imide, and N ethylmaleimide [IC50 (concentration causing half-maximal inhibition) 7.5, 25 and 520 microM respectively]; however, it was unaffected by ouabain, azide or oligomycin. The SM-ATPase demonstrated a Km of 1.05 mM and a Vmax. of 225 nmol/min per mg of protein. Moreover, fine-structure cytochemical results demonstrated that the SM-ATPase was localized to the cytoplasmic lamina of the parasite SM. A method was devised for the isolation of SM-derived vesicles. These were used to demonstrate the proton-pumping capacity of the SM-ATPase. Cumulatively, these results constitute the first demonstration of a surface membrane proton-translocating ATPase in a parasitic protozoan. PMID- 2906240 TI - Intracellular localization of beta-glucuronidase in fibroblasts after direct transfer from macrophages. AB - The subcellular distribution of beta-glucuronidase acquired by deficient human fibroblasts during co-culture with peritoneal macrophages was compared with that taken up by receptor-mediated endocytosis. Labelled enzyme taken up via receptors was located initially in a low-density endosomal fraction and was transferred to lysosomes within a few minutes. The beta-glucuronidase acquired during 24 h of co culture was present almost entirely within lysosomes and had a distribution profile identical with that of endogenous beta-hexosaminidase. Monensin prevented transfer of radiolabelled enzyme from endosomes to lysosomes and had a similar effect on the distribution of enzyme acquired by direct transfer, causing beta glucuronidase to accumulate within endosomes. When the temperature was lowered from 37 degrees C to 19 degrees C, the rate of transfer of enzyme from endosomes to lysosomes was decreased during both direct transfer and indirect receptor mediated endocytosis. These results show that a lysosomal enzyme acquired by direct transfer during cell-to-cell contact follows a similar intracellular route and has a similar distribution to that of enzymes taken up via cell-surface receptors. PMID- 2906241 TI - Preferential localization of rat liver D-myo-inositol 1,4,5-trisphosphate/1,3,4,5 tetrakisphosphate 5-phosphatase in bile-canalicular plasma membrane and 'late' endosomal vesicles. AB - Previous studies have shown that most of the inositol 1,4,5 trisphosphate/inositol 1,3,4,5-tetrakisphosphate 5-phosphatase activity of rat hepatocytes is associated with the plasma membrane [Shears, Parry, Tang, Irvine, Michell & Kirk (1987) Biochem. J. 246, 139-147]. We now show that the specific activity of this enzyme is highest in the bile-canalicular domain of the plasma membrane, at the opposite pole of the hepatocyte from the presumed site of receptor-mediated formation of inositol 1,4,5-trisphosphate. In intact hepatocytes and in sealed membrane vesicles originating from the bile-canalicular domain of the plasma membrane, the 5-phosphatase activity was mostly latent and therefore located at the cytoplasmic surface. A substantial amount of 5 phosphatase was also found in rat liver endosomal fractions, particularly a 'late' endosomal subfraction, indicating that this enzyme may be transported between the sinusoidal plasma membrane and other cellular membranes. PMID- 2906243 TI - [Pharmacological characterization of the new highly potent beta-adrenergic receptor blocker soquinolol]. AB - The present pharmacological test results characterize soquinolol (5-[3-tertiary butylamino-2-hydroxypropoxy]-2-formyl-1,2,3,4- tetrahydroisoquinoline mucate, We 704, Sertum) as a highly potent non-subtype-selective beta-adrenergic receptor blocker, which is devoid of any intrinsic sympathomimetic activity. Its localanaesthetic activity (membrane stabilizing effect) is very weak. It also shows good enteral efficacy and long duration of action. In binding studies with heart (Ki beta 1 = 3.25 nmol/l) and lung membranes (Ki beta 2 = 0.85 nmol/l) its binding profile was found to be similar to that of propranolol. Soquinolol inhibits the isoprenaline-induced tachycardia (EC50% = 48 micrograms/l) in the guinea-pig Langendorff heart in vitro to the same degree as propranolol. However, in the conscious dog soquinolol's beta 1-adrenergic blocking activity (ED 50%) on intravenous injection (5.5 micrograms/kg) and oral administration (5.8 micrograms/kg) is about twice as great as that of pindolol and 19 times (i.v.) or 138 times (p.o.) greater than that of propranolol. These results suggest 95% enteral efficacy for soquinolol (pindolol 88%, propranolol 13%). The differences in soquinolol's and propranolol's efficacy detected in vitro and in vivo are partially attributable to differences in their kinetic properties namely the lower protein binding and the higher distribution volume of soquinolol. In the conscious dog, soquinolol inhibits beta 1-(ED 50% = 4.0 micrograms/kg) and beta 2 receptors (ED 50% = 2.7 micrograms/kg) at dose levels which do not differ significantly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2906242 TI - Glutamine as a major nitrogen carrier to the liver in suckling rat pups. AB - We measured the amino acid concentrations in the afferent and efferent vessels of the liver in anaesthetized fed adult rats and in fed suckling rat pups. A much higher content of glutamine in the portal vein and the aorta than in hepatic veins suggests that this amino acid is actively taken up by the liver of fed suckling rat pups, conversely to what is found in adult rats. In an attempt to characterize further the mechanism(s) contributing to this enhanced glutamine uptake, we monitored the time course of 1 mM-glutamine transport into plasma membrane vesicles purified from the livers of either adult or suckling rats. The concentrative Na+-dependent uptake of glutamine was lower in those vesicles obtained from pups than in those obtained from adult rats. Glutaminase and glutamine synthetase activities in livers from both experimental groups were also measured. Glutaminase and glutamine synthetase activities in suckling rats were about 3-fold higher and 2-fold lower respectively than those in adult rats. It is concluded that glutamine is a main nitrogen carrier to the liver in fed suckling rats. A high availability of this amino acid and an enzyme imbalance between glutamine-synthesizing and -degrading activities may account for the net uptake found in vivo. PMID- 2906244 TI - Effects of bunitrolol on myocardial contractility and left ventricular myosin isoenzyme pattern. AB - Effects of long term treatment of hypertension with bunitrolol on myocardial contractility and left ventricular myosin isoenzyme pattern were examined. Male 22-week-old spontaneously hypertensive rats were treated with bunitrolol (30-40 mg/kg/d, p.o.) for 8-10 weeks. The blood pressure of the bunitrolol-treated group did not differ from that of the untreated group, but ratio of ventricular weight to body weight was significantly lower in the treated group. There were no significant differences in isometric developed tension and dT/dtmax of isolated left ventricular papillary muscles between bunitrolol-treated and control groups. Myocardial mechanical responses to isoprenaline (isoproterenol) also showed no differences between the two groups. Left ventricular myosin isoenzyme pattern obtained by pyrophosphate gel electrophoresis was significantly shifted to VM-1 by bunitrolol treatment. PMID- 2906245 TI - Pharmacological properties of the positive inotropic and alpha 1-adrenoceptor blocking agent saterinone. AB - The pharmacological properties of saterinone [+/-)-1,2-dihydro-5-[4-[2-hydroxy-3 [4-(2-methoxyphenyl)-1-piperazinyl] propoxy]phenyl]-6-methyl-2-oxo-3-pyridine carbonitrile, BDF 8634) were investigated in isolated organs of the guinea pig and in human platelets. Saterinone was found to be a potent antagonist at vascular alpha 1-adrenoceptors with a pA2-value of 8.46 +/- 0.12. Besides its affinity for alpha 1-adrenoceptors saterinone exerted a positive inotropic effect in the isolated papillary muscle at an EC50-value of 3.2 X 10(-6)mol/l indicating 10-fold greater potency than milrinone. Comparable EC50-values were also found for the inotropic, chronotropic and bronchodilatory actions of the drug, indicating a common mechanism for these effects. The inotropic effects were not mediated by beta-adrenergic or H2-histaminergic receptors, but were shown to involve an elevation of myocardial cyclic adenosine monophosphate (cAMP) content. Saterinone also inhibited crude cAMP phosphodiesterase (PDE) activity in homogenates obtained from guinea pig right ventricles. The IC50-value for PDE inhibition was 2.3 X 10(-5) mol/l and thus at a higher concentration than the inotropic effect. Saterinone was a potent inhibitor of human platelet aggregation induced by adenosine diphosphate, collagen and arachidonate. Against the latter agonist, saterinone was about 40-fold more effective than acetylsalicylic acid. In conclusion, saterinone exhibited a dual mechanism of action--direct inotropic effects in the myocardium and alpha 1-receptor blockade in the guinea pig vasculature.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2906246 TI - Electrophysiologic effects of saterinone and milrinone in the isolated guinea pig myocardium. AB - The positive inotropic agent milrinone and the newly synthesized compound saterinone [+/-)-1,2-dihydro-5-[4-[2-hydroxy-3-[4-(2-methoxyphenyl)-1 piperazinyl] propoxy]phenyl]-6-methyl-2-oxo-3-pyridine-carbonitrile, BDF 8634) dose-dependently increased the contractile force of guinea pig left atria. During a 90-min exposure, 10(-4) mol/l saterinone caused a continuous increase of the functional refractory period (FRP), while the initial positive inotropic effect faded gradually. No change of the FRP was observed with milrinone. Saterinone (10(-4) mol/l) also increased the action potential duration and the FRP of guinea pig papillary muscles, while milrinone had no influence on either parameter. Both milrinone and saterinone increased the amplitude, depolarization velocity and duration of slow response action potentials in K+-depolarized muscles. These effects appeared in the presence of tetrodotoxin or propranolol and could be reversed by carbachol. It is concluded that saterinone increases the force of contraction and the slow inward current by inhibiting cardiac phosphodiesterase. The increase of the FRP may be attributed to a decrease of the membrane K+ conductance. PMID- 2906247 TI - Positive inotropic and vasodilatory actions of saterinone in vivo. AB - The cardiovascular actions of the newly developed inotropic and alpha 1-receptor blocking agent saterinone [+/-)-1,2-dihydro-5-[4-[2-hydroxy-3-[4-(2 methoxyphenyl)-1-piperazinyl] propoxy]phenyl]-6-methyl-2-oxo-3-pyridine carbonitrile, BDF 8634) was investigated in small laboratory animals in vivo. Saterinone caused a direct inotropic effect in pithed guinea pigs without affecting heart rate. In the same animal species saterinone competitively antagonized the pressor effects of phenylephrine at inotropic doses. In conscious rabbits saterinone exerted dose-dependent increase in left ventricular dP/dtmax and in heart rate, whilst reducing arterial blood pressure in the same dose range. The drug dose-dependently antagonized phenylephrine as evidence of its alpha 1-receptor blocking effects in the conscious rabbit. The duration of alpha 1-receptor blockade was longer than the duration of inotropic effects. The onset of inotropic and vascular effects of saterinone was found to be simultaneous, when the drug was slowly infused into the femoral vein of anesthetized cats. The saterinone dose which caused a significant inhibition of the pressor effects of phenylephrine (comparable to prazosin) still caused a reduction of femoral perfusion pressure and systemic blood pressure in anesthetized cats pretreated with phenoxybenzamine. Thus in contrast to prazosin, which was rendered ineffective after phenoxybenzamine, saterinone possesses an additional mechanism for vasodilation. Saterinone exhibited good oral efficacy in spontaneously hypertensive rats and in conscious cats, in which an oral dose of 10-30 mg/kg significantly reduced arterial blood pressure or increased left ventricular dP/dtmax, respectively. Thus saterinone exerts in vivo direct positive inotropic and vasodilating effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2906248 TI - Vasodilating effect of the new beta-blocker tilisolol hydrochloride in humans. AB - The effects of a new beta-blocker, (+/-)-4-(3-tert-butylamino-2-hydroxypropoxy)-2 methyl-1(2H)-isoquinolino ne hydrochloride (tilisolol hydrochloride, N-696), on forearm circulation were examined and compared with those of propranolol in healthy young males. N-696 (30 mg/d for 7 days) decreased heart rate from 75 +/- 4 to 56 +/- 2 bpm (p less than 0.01) and decreased mean blood pressure from 86 +/ 2 to 79 +/- 2 mmHg (p less than 0.05) (n = 7). Propranolol (60 mg/d for 7 days) decreased heart rate from 62 +/- 1 to 51 +/- 2 (p less than 0.01) and decreased mean blood pressure from 83 +/- 3 to 73 +/- 3 mmHg (p less than 0.01) (n = 7). Resting forearm blood flow and forearm vascular resistance were not altered by N 696, whereas propranolol decreased forearm blood flow (p less than 0.05) and increased forearm vascular resistance (p less than 0.01). Reflex forearm vasoconstriction was examined by measuring forearm vascular resistance with a strain gauge plethysmograph during lower body negative pressure (LBNP). The regression line relating central venous pressure and forearm vascular resistance during LBNP was shifted toward the resistance axis by propranolol but was not altered by N-696. Propranolol augmented forearm vascular responses to intraarterially infused norepinephrine but N-696 did not alter them. Thus, in contrast to propranolol, N-696 lowered blood pressure and heart rate without peripheral vasoconstriction and did not augment forearm vasoconstrictive responses to norepinephrine. PMID- 2906249 TI - [Experimental cerebral vasospasm induced by oxyhemoglobin and the sympathetic nervous system (Part 1): Effect of alpha-adrenergic receptor blockers]. AB - This study was performed as part of a series of investigations into the relation between cerebral vasospasm following subarachnoid hemorrhage and the sympathetic nervous system. We studied the effect of phenoxybenzamine chloride (POB) and prazosin hydrochloride (Prazosin) on the cerebral vasoconstriction in the basilar arteries of cats induced by application of oxyhemoglobin (Oxy-Hb), noradrenaline (Nor) and prostaglandin F2 alpha (PGF2 alpha). Adult cats were anesthetized with intramuscular pentobarbital and maintained on a respirator through a tracheostomy. By the transclival approach, a bone window was formed in the clivus, and the dura was opened, exposing the basilar artery. A cannule was inserted into the subarachnoid space, and through it, Oxy-Hb, Nor and PGF2 alpha were injected. The sequential changes in caliber of the basilar artery were measured using photography. First, we determined the doses of POB and Prazosin necessary for decreasing the vasoconstriction induced by Nor, and 20 mg/kg of POB and 10 mg/kg of Prazosin were found to decrease the vasoconstriction induced by 10(-3) M Nor, statistically. Second, we investigated the effect of 20 mg/kg of POB and 0.5 mg/kg and 10 mg/kg of Prazosin on the cerebral vasoconstriction induced by Oxy-Hb or PGF2 alpha. POB (20 mg/kg) was infused for 2 hours before the application of Oxy-Hb or PGF2 alpha. Prazosin was given intravenously. In the first group, 0.02% Prazosin (0.5 mg/kg) was administered intravenously for 1.5 hours before the application of Oxy-Hb or PGF2 alpha. In the second group, 1.5 hours elapsed between the beginning of Prazosin (10mg/kg) infusion and the application of Oxy-Hb or PGF2 alpha.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2906250 TI - Cyclic GMP in cell function. PMID- 2906251 TI - Does beta adrenergic blockade influence the prognostic implications of post myocardial infarction exercise testing? AB - The influence of beta blockade on the ability of ST depression, during pre discharge exercise testing, to predict coronary anatomy and subsequent complications was studied in 300 consecutive post-infarct patients, 125 of whom underwent cardiac catheterisation. At the time of exercise 62 patients were taking a beta blocker. The exercise test had a higher sensitivity in predicting multivessel disease in patients who were not taking beta blockers than in patients who were (95% v 76%). beta Blockade did not, however, influence the ability of the test to identify patients at risk of subsequent cardiac events (sensitivity 84% and 85% respectively). These results suggest that it is not necessary to stop treatment with beta blockers before predischarge exercise testing of patients who have had an acute myocardial infarction. PMID- 2906252 TI - Immunoreactivity of various peptides in typical and atypical bronchopulmonary carcinoid tumours. AB - The presence of a number of regulatory peptides (bombesin, gastrin, glucagon, somatostatin, calcitonin and ACTH) was compared in 30 typical carcinoid tumours and 27 well differentiated neuroendocrine carcinomas (atypical carcinoids) using conventional immunocytochemistry. Strong immunostaining for one or more peptide was observed in 97% of the typical carcinoids (29/30) whereas only 67% of the neuroendocrine carcinomas showed immunoreactivity. The peptide most frequently detected in typical carcinoids was bombesin (67%), while gastrin was more common in neuroendocrine carcinomas (44%). Immunoreactivity for more than one peptide was present in 33 tumours and in three cases, six different peptides were detected. The study shows that immunoreactivity to various peptides is more common in typical carcinoids than well differentiated neuroendocrine carcinomas. The significance of these findings is discussed. PMID- 2906253 TI - Genetically homozygous choriocarcinoma following pregnancy with hydatidiform mole. AB - Genetic studies have been made in two cases of primary choriocarcinoma from patients in whom the antecedent pregnancy was a hydatidiform mole. Restriction fragment length polymorphisms of the DNA from the tumour, the patient and her partner were examined and in both cases the tumours were shown to be androgenetic in origin, having only paternal polymorphisms. While one tumour was shown to be heterozygous, two different paternal alleles being demonstrated with some probes, the other tumour was shown to be homozygous for all informative polymorphisms examined. Thus choriocarcinoma can follow complete hydatidiform mole which may be either heterozygous or homozygous. PMID- 2906255 TI - Clinical pharmacokinetics of etintidine. AB - The pharmacokinetics of etintidine (E), a potent H2 blocker, were studied in 12 normal, fasted subjects. The subjects received five ascending doses of E HCl in capsules at 72-h intervals. Blood and urine samples were collected and the plasma and urine levels of E were determined by HPLC. Following oral administration, plasma E levels showed double peaks in half of the subjects. Mean Cmax (0.42, 2.11, 3.82, 4.50, and 7.15 micrograms ml-1), AUC0-infinity (0.96, 4.94, 11.3, 17.5, and 24.5 h micrograms ml-1), and the amount of E excreted unchanged in 72 h (20, 54.8, 170, 320, and 371 mg) were determined. These parameters indicate the amount of E absorbed increased linearly with dose for each individual. Renal clearance was independent of the dose and the mean value (16.6 lh-1) was about twice that of the creatinine clearance (which did not significantly change as a result of E treatment), indicating that E is actively secreted into the renal tubules. As E was eliminated rapidly from the body (t1/2 less than 2 h), no substantial accumulation of E is expected after multiple dose treatment. PMID- 2906254 TI - The value of tumour markers in lung cancer. AB - The pre-treatment serum levels of neuron-specific enolase (NSE), phosphohexose isomerase (PHI) and circulating immune complexes (CC) as tumour markers were compared to measurements of standard haematology and biochemical indices in 73 patients with lung cancer, as an aid to differentiation of tumour type, estimating disease extent, predicting response to therapy and prognosis. Elevated NSE greater than or equal to 12.5 ng ml-1, PHI greater than or equal to 55 mgl-1 levels were observed in 55% of cases for NSE, 90% for PHI and 49% for CC. NSE was significantly elevated in 61% (25/41) of patients with SCLC (P less than 0.005) compared to 41% (13/32) with NSCLC. CC levels were significantly raised in 72% (23/32) of patients with NSCLC (P less than 0.05) compared to 32% with SCLC. The levels of NSE and PHI were not related to tumour stage but CC was significantly raised in limited compared to extensive disease in SCLC (P less than 0.05). Serum albumin was significantly lower in NSCLC compared to SCLC, and median values of alkaline phosphatase, gamma-glutamyltranspeptidase and aminoaspartate transferase were significantly higher in patients with extensive disease. The pre-treatment serum values of NSE, PHI, and CC did not predict the response to therapy or prognosis in the 73 patients with lung cancer. The most important prognostic factor was the number of abnormal routine laboratory parameters (greater than 4) in this group of patients. PMID- 2906256 TI - The behaviour of activity of selected enzymes in urine and in serum in experimental intoxication of animals with sublimate (mercury chloride). Part I. Acute intoxication. AB - In the work the behaviour of activity of selected enzymes in urine and in serum of experimental animals, which were intoxicated in an acute way, is presented. In the investigations there was observed the increase of activity of alkaline phosphatase in urine, simultaneous with its decrease in serum, the increase of GGTP in urine and shift in the composition of LDH isoenzymes in direction of slow migrating fractions. PMID- 2906257 TI - Hazardous side effects of the phenothiazine drugs. PMID- 2906258 TI - Diabetes in patients with hypertension receiving pharmacological treatment. PMID- 2906259 TI - Duodenal ulcers that are difficult to heal. PMID- 2906260 TI - Intravenous methylprednisolone in the treatment of Graves' ophthalmopathy. AB - Eleven euthyroid patients with severe Graves' eye disease were treated with intravenous methylprednisolone and followed up for six months or more by ophthalmological assessment, orbital computed tomography (CT), photographs, and antibody measurements. Papilloedema resolved in the single patient in whom it was present; visual acuity was abnormal in seven eyes initially and in only one eye after treatment; the intraocular pressure differential, which reflects muscle dysfunction, was initially abnormal in 18 eyes but showed a progressive and distinct improvement; nine patients showed substantial improvement in inflammatory signs. Exophthalmos improved early after treatment, but this improvement was not maintained. Orbital CT showed a pronounced reduction in the bulk of eye muscles after treatment in eight of nine patients. Autoantibodies to the thyroid stimulating hormone receptor declined. Adverse effects were trivial. Thus eight patients showed a clear response to intravenous methylprednisolone as judged by ophthalmic assessment and CT scan. The two patients who showed little response and one who had none all had a long history (more than a year) of ophthalmopathy. Results were better than those with oral steroids and adverse effects less. Treatment of Graves' eye disease is more likely to be effective if given early; patients should be referred promptly to specialist centres, where treatment with intravenous methylprednisolone should be considered. PMID- 2906261 TI - Long term H2 antagonists in peptic ulcer disease. PMID- 2906263 TI - Fatigue and fatigability. PMID- 2906262 TI - Cell cycle-related proteins: a flow cytofluorometric study in human tumors. AB - We used 2-parameter flow cytometry (FCM) to investigate the relationship between the cell cycle phases and 3 proteins whose expression is known to increase in proliferating cells: the surface antigen transferrin receptor (Trf-r), the "cyclin" (a proliferating cell nuclear antigen, PCNA), and the nuclear antigen recognized by the monoclonal antibody (MoAb) Ki-67. FITC-labeled antibodies against Trf-r, PCNA, and the Ki-67-reactive antigen, as well as propidium iodide DNA distribution, were simultaneously measured on human leukemia HL-60 and K562, and breast carcinoma MCF-7 cell lines and on fresh human leukemic and glioblastoma cells. The 70% ethanol fixation for Trf-r and PCNA and the 95% acetone fixation for Ki-67 plus permeabilization (with 0.1% and 1% Triton X100, respectively, for the surface and the nuclear antigens) produced cell suspensions with negligible cell clumping, high-quality DNA profiles, and bright specific immunofluorescent staining. The investigated proteins have different relationships with the proliferative state of the cell. Trf-r is expressed mainly at the transition from G0/G1 to S-phase. PCNA expression is prominent in late G1 and through S-phase and decreases in G2-M. The Ki-67-reactive antigen is widely distributed in G1, S, and G2-M phases. Knowledge regarding the relationships between proliferation-associated antigens and cell cycle phase in normal and neoplastic cells could improve our understanding of the mechanisms underlying growth regulation and neoplastic transformation. Bivariate FCM is an easy method for obtaining these data from large numbers of cells. PMID- 2906264 TI - Fluvoxamine and hepatic function. PMID- 2906266 TI - Putative neurotransmitters in the rat cochlea at several ages. AB - We have performed a longitudinal study of the content of the putative neurotransmitter substances, enkephalin, dynorphin, and acetylcholine (ACh), in the cochlea of the Fischer 344 rat. It is the first study of transmitters in the rat cochlea over an extended time span. This study also provides biochemical verification of the presence of ACh in cochlear tissues. No change was seen in the cochlear content of these transmitter candidates up to 24 months of age. PMID- 2906265 TI - Differential susceptibility of prevertebral and paravertebral sympathetic ganglia to experimental injury. AB - To investigate the response of selected sympathetic ganglia to experimental injury, neonatal rat pups were treated with either 6-hydroxydopamine (6-OHDA), guanethidine, or antiserum to nerve growth factor (anti-NGF). When examined at one month of age, each of the treatments resulted in a significantly greater loss of neurons and tyrosine hydroxylase activity in paravertebral (superior cervical and stellate) versus prevertebral (superior mesenteric and celiac) sympathetic ganglia. Guanethidine treatment produced the largest differential in neuron loss and tyrosine hydroxylase activity between pre- and paravertebral ganglia. Histologically, the acute phase of guanethidine-induced injury in the superior cervical, paravertebral, ganglia was characterized by a prominent mononuclear cell infiltrate and extensive neuronal degeneration. Minimal histopathologic changes were seen in the superior mesenteric, prevertebral, ganglia of the same animals. Immunolocalization of tyrosine hydroxylase and neuropeptide Y (NPY) in guanethidine-treated animals showed a preferential loss of sympathetic innervation of the extramural mesenteric vasculature with relative sparing of the noradrenergic innervation of Auerbach's myenteric plexus. Differences in the susceptibility of sympathetic ganglia to various insults may underlie the selective and heterogeneous involvement of sympathetic ganglia in clinical and experimental situations. PMID- 2906268 TI - Synapses from bipolar cells onto dopaminergic amacrine cells in cat and rabbit retinas. AB - Dopaminergic amacrine cells in the vertebrate retina have long been characterized as 'interamacrine' as they were only found to be pre- and postsynaptic to other amacrine cells. Immunohistochemistry with antibodies directed against tyrosine hydroxylase (TH) revealed synapses from bipolar cell axon terminals to TH containing neuronal processes at ribbon synapses in the rhesus monkey retina. This finding challenged the notion of the dopaminergic amacrine cell phenotype as 'interamacrine'. In order to determine if the finding of synapses from bipolar cells to dopaminergic amacrine cells could be generalized to other species, we studied the synaptic organization of dopaminergic amacrine cells in the retinas of cats and rabbits with electron microscopy of TH immunoreactivity. In both species, TH-immunoreactive processes were found to be postsynaptic to bipolar axon terminals at ribbon synapses demonstrating that the original finding in the primate may be a significant feature in the retinas of many other vertebrates as well. PMID- 2906267 TI - Buspirone, 8-OH-DPAT and ipsapirone: effects on hippocampal cerebellar and sciatic fiber excitability. AB - The effects of serotonin (5-hydroxytryptamine; 5-HT), and the novel anxiolytics buspirone, 8-OH-DPAT (8-hydroxy-2-[N,N-dipropylamino]-tetralin) and ipsapirone (TVXQ 7821, 2-[4-[4-[2-pyrimidinyl]-1-piperazinyl] butyl]-1,2-benzisothiazol 3[2H]one-1,1-dioxide-hydrochloride) on fiber excitability were studied in three axon systems; hippocampal Schaffer collateral fibers, cerebellar parallel fibers, and sciatic nerves. In the hippocampus, application of buspirone, 8-OH-DPAT and ipsapirone resulted in reversible, dose-dependent reductions in the amplitude and conduction velocity of action potentials recorded from presynaptic afferent fibers. Although these agents bind to 5-HT1A receptors, 5-HT application, even at very high (1 mM) concentrations, did not alter axonal responses. This suggests that buspirone, 8-OH-DPAT and ipsapirone exert an action independent of a serotonergic mechanism. Similar effects were observed on the cerebellar parallel fibers although the cerebellum does not have an appreciable number of 5-HT1A receptors. To examine the generalized effects of these agents on nerve excitability, rat sciatic compound action potentials were studied with sucrose gap recordings. Whereas 5-HT, 8-OH-DPAT and ipsapirone had no effects even at high concentrations (1 mM), application of buspirone led to reversible decrement of the responses without appreciable change in membrane potential. These results indicate that buspirone, 8-OH-DPAT and ipsapirone have actions on the excitability of hippocampal and cerebellar neurons independent of serotonergic mechanisms. Moreover, buspirone, but not 8-OH-DPAT or ipsapirone, produces decreased sciatic nerve excitability. NS 20393 PMID- 2906269 TI - Electrophysiological studies on the spinal effects of dermorphin, an endogenous mu-opioid agonist. AB - The intrathecal administration of dermorphin, an endogenous heptopeptide first discovered in amphibia, produces dose-dependent selective inhibitions of C fibre evoked responses in rat dorsal horn nociceptive neurones (ED50 0.11 micrograms). Naloxone (10 micrograms) but not ICI 174,864 (125 micrograms) antagonised the effects of the peptide. A beta-fibre-evoked activity was relatively unaffected. Thus dermorphin can profoundly inhibit nociceptive afferent input in the spinal cord, and in this preparation is more potent (approximately 40X) than morphine. PMID- 2906270 TI - Dipeptidylpeptidase IV activity in Meissner corpuscles of rhesus monkey and its possible function. AB - Histochemical investigation by means of light and electron microscopy revealed the presence of dipeptidylpeptidase IV activity in Meissner corpuscles of macaque glabrous skin. The enzyme activity was found in fibroblast-like cells forming an incomplete capsule around the Meissner corpuscle. Distinct electron-dense reaction product due to dipeptidylpeptidase IV activity was consistently localized in the plasma membrane of specialized Schwann cells enveloping the unmyelinated portion of sensory axons. Their axolemma was devoid of dipeptidylpeptidase IV reaction product. The membrane-bound dipeptidylpeptidase IV activity presented here and the occurrence of substance P-containing nerve fibers in primate Meissner corpuscles referred to elsewhere, suggest the possible functional involvement of the enzyme in the production of substance P fragments, influenced in different ways by the axon proper and its surrounding Schwann cells. PMID- 2906271 TI - Tyrosine hydroxylase-containing neurons in the supraoptic and paraventricular nuclei of the adult human. AB - We have studied the distribution of tyrosine hydroxylase-containing neurons in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the adult human hypothalamus. Large numbers of these neurons were seen in these hypothalamic nuclei; approximately 40% of all the cells within the SON and PVN were immunoreactive for tyrosine hydroxylase (TH-ir). Most of these cells were magnocellular. Their distribution was compared to that of arginine-vasopressin immunoreactive (AVP-ir) cells. In the SON a greater proportion of magnocellular TH-ir cells was found caudally compared to AVP-ir cells. In the PVN the magnocellular TH-ir cells were larger in mean diameter compared to AVP-ir cells. In double-immunofluorescence experiments some TH-ir cells contained oxytocin immunoreactivity but none contained AVP-ir. In the adult human a large number of PVN and SON magnocellular cells appear to synthesize a catecholamine. A subclass of these neurons also synthesize oxytocin but most cells are distinct from the classically described neurosecretory neurons. PMID- 2906272 TI - Reduced glutamate binding in rat dorsal vagal complex after nodose ganglionectomy. AB - Quantitative receptor autoradiography with L-[3H]glutamate was employed to examine the distribution and properties of glutamate binding sites in the rat brain 14 days after excision of the right nodose ganglion. Slide-mounted coronal sections of the brain showed reduced L-[3H]glutamate binding in the nucleus tractus solitarius/dorsal motor nucleus of the vagus in the ipsilateral relative to the sham-operated side. Densitometric and saturation analyses of binding data indicated a significant reduction in the density of glutamate binding sites (57% decrease relative to sham), while there was a significant increase in receptor affinity (40% greater than sham). Binding was unaltered in the inferior olivary complex. Glutamate receptors are likely to exist on synaptic nerve terminals of vagal afferent fibres within the nucleus tractus solitarius and on vagal preganglionic neurones within the dorsal motor nucleus of the vagus and/or their dendritic processes within the nucleus tractus solitarius. Additionally, our receptor autoradiographic studies provide evidence for L-glutamate being a transmitter of vagal afferent neurones. PMID- 2906273 TI - Evolutionary and comparative aspects of nociception. AB - The ability to detect and respond to aversive environmental stimuli is a basic feature of animals that is expressed in the term 'nociception.' Nociception and nociceptive responses provide an index of the sensitivity of individuals to aversive physical stimuli. Measurements of alterations in nociceptive responses (antinociception and analgesia) are commonly used to monitor the behavioral and physiological status of animals following experimental manipulation that usually, but not always, involve exposure to either noxious, stressful or potentially stressful physical and/or biological stimuli. This review briefly considers: i) the phylogenetic development of nociceptive responses and behaviors ii) evolutionary and comparative patterns of the neuromodulation of nociceptive behaviors by opioid peptides and other nonopioid peptidal regulatory mechanisms; iii) the effects of various biological variables, including; age, development, sex, and temporal factors (biological rhythms) on nociception in rodents. PMID- 2906274 TI - Pain relief in burns--how we do it. PMID- 2906275 TI - Calcium dependent regulation of catecholamine and serotonin metabolism in human neuroblastoma cells. AB - Three human neuroblastoma cell lines were shown to have markedly different contents of catecholamines and serotonin. Two of the cell lines (CHP-134 and IMR 5) have higher levels of dopamine and its metabolites, while CHP-404 cells have higher levels of serotonin and its metabolites. Each cell line responded to the addition of D,L-2-amino-5-phosphonovalerate, an agent which increases plasma membrane permeability to Ca2+ (Pastuszko and Wilson, 1988; with striking changes in the metabolism of the neurotransmitters. These changes were dependent on the extracellular calcium concentration and include activation of dopamine synthesis (tyrosine hydroxylase), increased levels of dihydroxyphenylacetic acid and increased formation of N-methylated dopamine derivatives. Catabolism of serotonin to 5-hydroxyindole acetic acid was inhibited while that to 5-hydroxytryptophol was stimulated. These data clearly identify several important sites for regulation of neurotransmitter metabolism by calcium. The mechanisms, direct or indirect, by which the enzyme activities are modulated by calcium remain to be established. PMID- 2906276 TI - Prospects for cancer prevention through genetics: family studies and population screening. AB - The ultimate goal of all genetic analyses, whether at the statistical or molecular level, is to identify individual genes and their function. The application of genetic epidemiological tools to common diseases, together with the recent implementation of recombinant DNA methodology, makes it feasible to identify, characterize, and even isolate genes involved in the major diseases of mankind. This paper outlines how the classical epidemiologic approach interfaces with the new DNA technologies. We review the progress of restriction fragment length polymorphism analyses in family studies and address their current and potential use in studies of unrelated individuals. In addition, we briefly discuss the role that oncogenes and inherited genetic alterations seem to play in the development of human cancers. The use of these techniques provides a framework for a better understanding of cancer etiology and may eventually help to define strategies for cancer prevention. PMID- 2906278 TI - Role of astroglial cell clones in the survival and differentiation of cerebellar embryonic neurons. AB - To investigate the role of astrocytes in the survival and differentiation of cerebellar neurons during development, we have used astroglial cell clones, derived from 8-day postnatal cerebellar explants and which might be the in vitro equivalents of the 3 main types of cerebellar astrocytes, the Golgi epithelial cells and their Bergmann processes, the velate protoplasmic and the fibrous astrocytes (F. Alliot and B. Pessac, Brain Res., 306 (1984) 283-291). Nearly all single cells, dissociated from 15-day embryonic mouse cerebella and seeded at low density, adhered to layers of each of the cerebellar astroglial cell clones as well as to other glial lines or artificial substrates. However, the cerebellar embryonic neurons survived well only on monolayers of either the 'Golgi-Bergmann' like or the 'velate protoplasmic'-like clones. On these layers, 60-80% of the neurons were still present after 5 days of co-culture, while only less than 5% survived on the other types of substrates. The differentiation pattern of the neurons surviving on the 'Golgi-Bergmann' and the 'velate protoplasmic' astroglial clones was studied with markers of postmitotic granule cells, the major neuronal population in adult cerebellum. The velate protoplasmic-like clone was the only one able to support the coordinate acquisition by most surviving neurons of the phenotypic characteristics of granule cells, i.e. a distinct morphology, a specific epitope binding the monoclonal antibody 7-8 D2 and immunoreactivity to glutamate. These data show a broad heterogeneity in the capacity of astroglial cell clones to support embryonic cerebellar neurons. In addition, they indicate that neuronal survival per se is not sufficient for the acquisition of a differentiated neuronal phenotype. PMID- 2906277 TI - Further studies of the effects of somatostatin and related peptides in area CA1 of rabbit hippocampus. AB - 1. In slice studies of mature and immature CA1 hippocampal pyramidal cells from rabbit, somatostatin 14 (SS14), the related peptide somatostatin 28(1-12) [SS(1 12)], and the synthetic analogue of somatostatin 14, SMS-201995 (SMS), had similar effects. When pressure-ejected onto cell somata, these peptides elicited depolarizations, often accompanied by action potential discharge. When applied to dendrites, the peptides produced depolarizations or hyperpolarizations. 2. When a large amount of one of the three somatostatin-related (SS) peptides was applied to the slice at some distance from the impaled cell, hyperpolarizations were observed that were not always blocked by tetrodotoxin (TTX) or low Ca2+. Since SS peptides were also found to depolarize interneurons in area CA1, it seems likely that the hyperpolarizations that were blocked by TTX or low Ca2+ were mediated via excitation of interneurons that in turn hyperpolarized pyramidal cells. 3. All SS peptides also had long-lasting effects on CA1 pyramidal cells that led to spontaneous firing of action potentials and an increase in the number of action potentials discharged in response to a given depolarizing current pulse; the spontaneous discharge effect was blocked by TTX or low Ca2+ plus Mn2+ and, thus, appeared to have a presynaptic mechanism. However, the increase in discharge in response to a constant depolarizing current pulse was not dependent on intact synaptic transmission and, therefore, was attributable to a direct postsynaptic effect of the SS peptides. PMID- 2906279 TI - The role of calmodulin in neurotransmitter release and vascular responsiveness in spontaneously hypertensive rats. AB - This study was designed to investigate the role of calmodulin in adrenergic transmission in hypertension. In perfused mesenteric vasculature from spontaneously hypertensive rats (SHR, 7-9 weeks of age) and age-matched Wistar Kyoto rats (WKY), the effects of a specific calmodulin antagonist (W-7) on norepinephrine overflow and vascular responsiveness to endogenous and exogenous norepinephrine were examined. The vasoconstrictor responses to electrical nerve stimulation and exogenous norepinephrine as well as norepinephrine overflow during electrical nerve stimulation were significantly enhanced in SHR compared with those in age-matched WKY. The calmodulin antagonist, W-7, reduced not only vasoconstrictor responses but also norepinephrine overflow during nerve stimulation. These inhibitory effects of W-7 were significantly greater in SHR than in WKY. The results demonstrate that norepinephrine overflow from the sympathetic nerve endings and vascular responsiveness were increased in SHR. The marked reduction in norepinephrine overflow and pressor responses by W-7 might suggest the greater calmodulin-dependent adrenergic transmission in this model of hypertension. PMID- 2906280 TI - Dipeptidyl peptidase IV--subcellular localization, activity and kinetics in lymphocytes from control subjects, immunodeficient patients and cord blood. AB - Dipeptidyl peptidase IV (DPIV), a T cell enzyme, has been implicated in the regulation of lymphocyte proliferation in response to lectins and allogeneic cells. A sensitive fluorimetric assay has been established for the enzyme and used to investigate DPIV activity, kinetics and the subcellular localization in lymphocytes from control subjects, cord blood and patients with common variable hypogammaglobulinaemia (CVH) and chronic lymphatic leukaemia (CLL). Using sucrose density gradient centrifugation and organelle marker enzyme assays, in conjunction with digitonin as a selective plasma membrane perturbant and diazotized sulphanilic acid as a non-permeant enzyme inhibitor, DPIV was shown to be a plasma membrane ecto-enzyme. A significant decrease in lymphocyte DPIV activity was observed in cord blood and in patients with CVH and CLL compared to controls. Kinetic analysis showed a marked decrease in the Vmax of lymphocyte DPIV from cord blood and patients with CVH and CLL compared to controls. The apparent Km for the substrate was unaffected in cord blood and patients with CLL. However, in patients with CVH the Km was significantly reduced. Various enzyme inhibitors showed no differences between control subjects and CVH lymphocyte activities. The decreased Km for DPIV provides further evidence for a stem cell defect rather than cell immaturity in CVH. PMID- 2906282 TI - The Drosophila homoeotic gene spalt is structurally related to collagen alpha 1(IV) chain. PMID- 2906281 TI - Immunomodulation by methimazole therapy in Graves' disease: rapid changes in activation stage of circulating regulatory T cell subsets, B cells and NK cells. AB - In patients with Graves' disease, initiation of thyrostatic therapy with methimazole causes a selective reduction of thyroid but not other autoantibody levels. The mechanism of this immunosuppressive effect is unknown. In the present study, methimazole (20 mg daily) induced very rapid changes in the surface antigen expression of several circulating lymphocyte subpopulations in six patients with Graves' disease. Within 1 to 3 days of therapy, the proportions of HLA-DR+ cells within the CD8+(Leu 2+) subset (activated 'suppressor/cytotoxic' T cells), CD11+(Leu 15+) cells out of CD8+ cells ('suppressor' T cells), and CD45+R (Leu 18+) cells out of CD4+(LEU 3+) cells ('suppressor/inducer' T cells) increased significantly from 4.7 +/- 3.9% to 9.5 +/- 6.0%, from 7.5 +/- 1.5% to 17 +/- 5.8% and from 49 +/- 17% to 73 +/- 19%, respectively. In parallel, the percentages of DR+ cells within the CD4+(Leu 3+) subset (activated 'helper' T cells), 4F2+ cells out of CD19+(Leu 12+) cells (activated B cells) and 4F2+ cells out of CD16+(Leu 11+) cells (activated 'natural killer'-like cells) declined significantly from 7.2 +/- 5.6% to 2.8 +/- 2.1%, from 7.2 +/- 1.5% to 4.0 +/- 2.8% and from 5.5 +/- 3.5% to 2.8 +/- 4.9% at 3 days, respectively. In contrast, no consistent phenotypic changes occurred in lymphocytes drawn from six healthy subjects during 7 days of methimazole medication. Direct in vitro effects of methimazole on lymphocyte markers were not observed when blood mononuclear cells from untreated patients were incubated with either the drug (10(-4) and 10(-6)M) or with autologous pre/post treatment serum for 1 to 4 days. Methimazole thus induces rapid alterations in the subclass and activation marker expression of circulating lymphocyte populations in Graves' disease. These alterations are compatible with a down-regulation of B cell activity. Indirect evidence suggests that the thyroid gland is the source of secondary signals for these changes to take place. PMID- 2906283 TI - Effects of varying doses of methionine sulfoximine on liver glutamine synthetase activity and time courses of blood and urinary nitrogenous compounds in the chicken (Gallus domesticus). AB - 1. The activity of liver glutamine synthetase was inhibited to 7-12% of the control activity by an intracardiac injection with methionine sulfoximine (MSM) at dosages of 20, 50, 75 and 100 mg/kg body wt. 2. Plasma glutamine concentrations in all the MSM treatments decreased sharply, then reached steady state levels within 0.5-2.5 hr, which were almost proportional to a dose of MSM. 3. Blood ammonia concentration sharply increased to a steady-state level attained at 4.5 hr, which was proportional to a dose of MSM. The excretion rate of urinary ammonia augmented linearly up to the dose dependent maximum rates within 2-5 hr. 4. Plasma uric acid concentration dropped linearly by about 6.4 mg/100 ml at doses of 50, 75 and 100 mg MSM and by 3.7 mg/100 ml at a dose of 20 mg MSM within 2.5 hr, then recovered a little. 5. The decreases in excretion rates of urinary uric acid for the first 4 hr were almost the same at doses of 50 mg and larger, being twice as large as that of the control chicken. 6. Any doses of MSM affected neither the time course of excretion rate of total urinary nitrogen nor its total amounts for 7 hr after MSM treatment. PMID- 2906284 TI - The effect of immunization against somatostatin on growth and concentration of somatotropin in plasma of Holstein calves. AB - Holstein calves were used to investigate the effects of immunization procedures against somatostatin (SRIF) on growth and concentrations of somatotropin in plasma. In Trial 1, eight heifers 37 weeks of age were inoculated with cyclic SRIF conjugated to human alpha-globulin. Final body weight, average daily gain, and measurements of body size were not significantly different between control and SRIF-immunized calves. Apparent total tract nutrient digestibilities and efficiency of feed utilization also were not significantly different between treatments. Plasma concentrations of somatotropin were increased and plasma concentrations of urea nitrogen were decreased in calves immunized against SRIF compared to controls, but these mean differences were not significant. In Trial 2, eleven bull calves seven weeks of age were inoculated with cyclic-SRIF conjugated to keyhole limpet hemocyanin. Calves immunized against SRIF had larger average daily gains (P less than .06) than did control calves. Body size, efficiency of feed utilization, and concentrations of somatotropin in plasma were not significantly different for SRIF immunized calves and control calves. Urea nitrogen in plasma was lower (P less than .04) for calves immunized against somatostatin than for control calves. Data indicate that Holstein calves can produce auto-antibodies against SRIF; however, additional research will be required before such immunization techniques can be effectively used to improve weight gains in cattle. PMID- 2906285 TI - Prescription of benzodiazepines in general practice in the county of Arhus, Denmark. AB - During one week in 1985, 227 general practitioners in the County of Arhus, Denmark, recorded their prescriptions of benzodiazepines. In all 2,812 prescriptions were recorded, for 2,574 patients. The sex ratio (male/female) was 1.0/2.0. The incidence of first-time prescriptions was 26.0 prescriptions/1,000 inhabitants/year. The prescription rate, calculated as defined daily doses/1,000 inhabitants/day, was highest for minor tranquillizers in the age group 60-69, whereas for hypnotics/sedatives it was highest in the age group 70+. Of minor tranquillizers, 83-84% were prescribed as anxiolytics, and of hypnotics/sedatives, 98% were prescribed as hypnotics. Only 18-28% of patients had a diagnosis of psychiatric illness. Between 62-75% of patients received no other treatment than a benzodiazepine prescription. At the time of the first prescriptions, 44-57% of the patients were mentally distressed. For about 33% of patients, a somatic illness was of essential importance for the prescription. Twenty-six percent of the men and 17% of the women taking benzodiazepines were recognized as real or potential abusers. Eighty-three percent of repeat prescriptions were prescribed through indirect contacts. PMID- 2906286 TI - [Traumatic injuries of teeth in children. Injuries to permanent teeth]. PMID- 2906287 TI - [Traumatic injuries to teeth in children. Complications]. PMID- 2906288 TI - Morphological, cytochemical and neuropharmacological evidence for the presence of catecholamines in hydrozoan planulae. AB - Planula larvae of Halocordyle disticha were examined for the presence of catecholamines using a multipronged approach. Transmission electron micrographs of planular sensory cells and ganglionic cells demonstrated dense-cored vesicles and electron-dense droplets in both cell types. These vesicles and droplets were similar in morphology to catecholamine-containing granules of vertebrates. Planulae processed with the SPG histofluorescence technique, specific only for catecholamines, exhibited blue-green fluorophores which were most prominent in the anterior ectoderm. Such fluorescence was associated with sensory cells, ganglionic cells and the neural plexus. Pretreatment of planulae with neuropharmacological agents which prevent reuptake (reserpine) or cause release (nicotine, ephedrine) of catecholamines caused a diminution of the fluorophores. Pretreatment of animals with 6-hydroxydopamine, which causes destruction of catecholamine-containing cells, prevented any fluorescent response. Ultrastructural examination of reserpine-treated planulae revealed a dramatic reduction in the populations of dense-cored vesicles and electron-dense droplets. Furthermore, many of the vesicles and droplets remaining in reserpinized animals appeared washed out, i.e. stained faintly. Exposure of planulae to exogenous norepinephrine caused premature, rapid metamorphosis and produced polyps with slightly stunted tentacles and pitted, irregular hypostomes. Exposure of planulae to nicotine caused similar effects. Rearing planulae in sea water containing alpha blockers, phentolamine and tolazoline, had no discernible effect on behaviour (motility, phototactic response) or gross morphology. However, planulae raised in sea water containing propranolol, a beta blocker, ceased all movement, became tack-shaped and died within 72 h. These results meet multiple criteria for the identification of catecholamines in hydrozoan planulae and suggest that such catecholamines may function as neurotransmitters, neurohormones or neuromodulators during larval development. PMID- 2906289 TI - Role of beta-adrenoreceptors in the inhibition of gastric acid secretion after duodenal acidification in dogs. AB - The role of the adrenergic system in the duodenal mechanisms that inhibit gastric acid secretion (GAS) after duodenal acidification (DA) was studied. In 12 mongrel dogs, with gastric and duodenal fistulas, six experiments were carried out evaluating pentagastrin-stimulated GAS and serum secretin levels: DA (HCl 2 ml/min) for 1 h (group A); DA (HCl 2 ml/min) for 1 h plus propranolol (group B); DA (HCl 2 ml/min) for 1 h plus phentolamine (group C); duodenal instillation of saline (2 ml/min) for 1 h (group D); (duodenal instillation of saline (2 ml/min) for 1 h plus propranolol (group E), and duodenal instillation of saline (2 ml/min) for 1 h plus phentolamine (group F). Significantly (p less than 0.05) high percentages of inhibition of GAS (49-70.5%) paralleled with increases of serum secretin levels (48.4-84%) were noted in group A and C experiments. However, DA did not inhibit GAS nor did it increase the levels of secretin in group B and D-F experiments. It is concluded that the inhibition of GAS after DA is controlled, at least in part, by the action of the beta-adrenoreceptors. PMID- 2906290 TI - Alpha 2-antagonist compounds and lipid mobilization: evidence for a lipid mobilizing effect of oral yohimbine in healthy male volunteers. AB - Investigations were carried out to analyse the interactions of alpha 2 antagonists (yohimbine, idazoxan, SK & F-86,466) with human fat cell alpha 2 adrenoceptors. All the alpha 2-antagonists enhanced the lipolytic potencies of epinephrine with an order of potency: yohimbine greater than idazoxan greater than SK & F-86,466; the same order was also found in 3H-yohimbine competition studies on human fat cell membranes. The most potent agent, yohimbine, was administered orally in humans to define the conditions of appearance and the time course of a putative lipid-mobilizing action. Oral yohimbine administration (0.2 mg kg-1) elevated plasma glycerol and non-esterified fatty acids in fasting healthy subjects without significant action on heart rate or blood pressure during the time-course of the experiment. The lipid-mobilizing action of yohimbine was reinforced during physical exercise, completely suppressed after a meal and partially blocked by administration of propranolol (0.5 mg kg-1; 60 min before yohimbine). Plasma norepinephrine concentrations were increased (40-50%) after oral yohimbine administration. The rise in plasma catecholamine concentration elicited by yohimbine was not modified by propranolol treatment. The lipid-mobilizing effect of yohimbine could be attributable to: (i) the increase in synaptic norepinephrine with a resultant increment in lipolysis by beta-adrenergic agonism; (ii) a decrease in alpha 2-adrenoceptor stimulation of human fat cell alpha 2-adrenoceptors; (iii) a blockade of presynaptic alpha 2 adrenoceptors. The use of highly selective alpha 2-antagonists will allow investigations into alpha 2-adrenoceptors, which may represent a novel locus for pharmacological intervention in lipid-mobilization strategies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2906291 TI - Electrophysiological evidence for a functional differentiation between subtypes of the 5-HT1 receptor. AB - Serotonin (5-HT) neurons in the dorsal (DRN) and median (MRN) raphe nuclei, and dopamine (DA) neurons in the substantia nigra (SN) were recorded extracellularly in the anesthetized rat. Compounds which have a relatively high affinity for the 5-HT1A or 5-HT1B subtypes of the 5-HT1 receptor were administered and their effect on the firing rate of the monoamine cells was determined. 5-HT1A ligands were more potent in inhibiting impulse activity in the DRN than in the MRN, but had little effect in the SN. In contrast, 5-HT1B ligands increased the firing rate of MRN 5-HT units at low doses, and were also effective inhibitors of DA cell firing in the SN. These results could be correlated with recently described differences in the distribution of the 5-HT1A and 5-HT1B receptor subtypes, and were interpreted as indicating possible functional differentiation between these subtypes. In particular, agonist activity at the 5-HT1B autoreceptor site may decrease 5-HT release, suggesting a presynaptic locus for this receptor in the somatodendritic region. The site also appears to be implicated in 5-HT modulation of nigral DA impulse flow. PMID- 2906292 TI - Thiocyanate stabilizes AMPA binding to the quisqualate receptor. AB - Calcium and chloride ions stimulated [3H]glutamate binding to quisqualate sensitive [3H]glutamate binding sites 4-fold, as measured by quantitative autoradiography, whereas 100 mM potassium thiocyanate had no additional effect. In contrast, calcium and chloride had little effect on the binding of [3H](RS) alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid ([3H]AMPA), but 100 mM thiocyanate stimulated binding 4-fold. AMPA displaced little [3H]glutamate binding from quisqualate-sensitive binding sites in the molecular layer of the cerebellum in the absence of thiocyanate. However, in the presence of thiocyanate AMPA became a more effective displacer, but still displaced only 44% of the quisqualate-sensitive [3H]glutamate binding. The distribution of [3H]glutamate binding to quisqualate-sensitive sites was similar to but not identical with that of [3H]AMPA binding. However, the distribution of AMPA-displaceable [3H]glutamate binding correlated highly (r = 0.97, P less than 0.0005) with that of [3H]AMPA binding. The results suggest that AMPA binds to a subclass of quisqualate sensitive [3H]glutamate binding sites that are highly influenced by ionic environment and that quisqualate-sensitive binding sites exist in several states. PMID- 2906293 TI - Regulation of beta-adrenoceptors by catecholamines in the rabbit skeletal muscle. AB - (-)-[125I]Cyanopindolol (ICYP) was used to characterise beta-adrenoceptors in the gastrocnemius muscle of the rabbit. The binding of ICYP was saturable. The KI value for the selective beta 2-adrenoceptor antagonist, ICI 118551, was 0.16 +/- 0.01 nM (mean +/- S.E.M) and for the selective beta 1-adrenoceptor antagonist, metoprolol, was 300.1 +/- 33.3 nM. Hofstee plots for both antagonists were linear indicating the presence of homogeneous beta 2-adrenoceptors in the skeletal muscle of the rabbit. In gastrocnemius muscles obtained from rabbits chronically pretreated in vivo with vehicle (0.1% ascorbic acid), adrenaline (40-50 nmol.kg 1.h-1) or noradrenaline (80-100 nmol.kg-1.h-1) via osmotic mini-pumps implanted for 10 days, the Bmax values were 44 +/- 3, 25 +/- 4 (P less than 0.05) and 41 +/ 7 (fmol.mg-1 protein) and KD values were 7.3 +/- 0.9, 6.3 +/- 0.8 and 9.3 +/- 2.5 (pM), respectively. Thus pretreatment with the circulating hormone adrenaline but not noradrenaline down-regulated the number of skeletal muscle beta 2 adrenoceptors but did not influence the affinity. PMID- 2906294 TI - Effects of benzylic hydroxyl substitution on the alpha-adrenoceptor blocking activity of tolazoline. AB - The R(-)- and S(+)-enantiomers of alpha-hydroxytolazoline, the benzylic hydroxy substituted derivative of the alpha-adrenoceptor antagonist, tolazoline, were evaluated at alpha 1- and alpha 2-adrenoceptors in canine saphenous vein. Benzylic hydroxyl substitution of tolazoline in either the R(-) or S(+) configuration significantly decreased affinity at both alpha 1- and alpha 2 adrenoceptors. Differences in affinity between the R(-)- and S(+)-enantiomers were small, which is characteristic of imidazolines, but in marked contrast to phenethylamines where enantiomeric differences are large. The rank order of affinities at alpha 1- and alpha 2-adrenoceptors is tolazoline greater than S(+) alpha-hydroxytolazoline = R(-)-alpha-hydroxytolazoline, which is different from that order predicted by the Easson-Stedman hypothesis (i.e., R(-) greater than S(+) = desoxy). The findings support our contention that phenethylamines and imidazolines interact differently with alpha-adrenoceptors. PMID- 2906295 TI - Neuronal death in vitro: parallelism between survivability of hippocampal neurones and sustained elevation of cytosolic Ca2+ after exposure to glutamate receptor agonist. AB - Hippocampal neurones isolated from rat embryos were maintained on glial monolayers in a medium containing no L-glutamate (Glu). The administration of Glu for a limited period induced a massive death (loss) of neurones. The degree of neuronal loss increased with time after exposure to Glu. The extent of neuronal loss assessed 24 h after exposure to Glu was dependent upon the concentration Glu and on the duration of the exposure. An increase in concentration of external Ca2+ during the exposure to Glu enhanced the extent of loss. By contrast, an increment in concentration of environmental Mg2+ reduced the loss. The inhibitor of spike firing, tetrodotoxin (TTX) and the suppressor of Ca2+ entry, nitrendipine, both decreased the extent of loss, when delivered prior to Glu. The toxicity of Glu became progressively more apparent with further days of culture. The cytosolic concentration of Ca2+ ([Ca2+]i) in single hippocampal neurones was monitored by microscopic fluorometry under conditions equivalent to those in the death assay. The time required for the recovery of [Ca2+]i from the level elevated by exposure to Glu to pre-stimulus levels closely paralleled the degree of neuronal loss; i.e. high doses of Glu, long periods of exposure, high concentrations of external Ca2+, low concentrations of external Mg2+, and extended days of culture all retarded [Ca2+]i recovery, while TTX and nitrendipine accelerated it. These findings show that neuronal death resulting from an extraneous excitation (excitotoxicity) can be analyzed in vitro. Furthermore, substantial support has been provided to the hypothesis that excitotoxicity has an underlying mechanism, an excess loading of Ca2+ in neuronal cytoplasm. PMID- 2906296 TI - Structural requirements for activation of excitatory amino acid receptors in the rat spinal cord in vitro. AB - The conformational requirements for activation of N-methyl-D-aspartate (NMDA) and quisqualate (QUIS) excitatory amino acid receptors on rat spinal neurones in vitro have been examined using a number of conformationally restricted compounds related to L-glutamate (L-GLU). The excitants were assigned to a receptor type on the basis of their susceptibility to blockade by D (-)-2-amino-5-phosphonvalerate (DAPV) and kynurenate (KYNA). When iontophoretically applied to unidentified neurones in the dorsal horn of spinal cord slices maintained in vitro, three of the isomers of 1-amino-1,3-cyclopentane dicarboxylate (ACPD) evoked excitations which were DAPV-sensitive and therefore were probably elicited via NMDA receptors. The fourth isomer (D-trans-(1R,3S)-ACPD) resembled quinolinate (QUIN) in its actions, and differed from both NMDA and QUIS. Several pyridine derivatives in addition to QUIN were tested, and both the 2,5- and 2,6-pyridine dicarboxylates evoked excitations which, like those produced by QUIS and L-GLU, were largely unaffected by both DAPV and KYNA and thus appeared due to activation of the QUIS receptor. 2,4-Pyridine dicarboxylate acted as a weak and unselective antagonist of amino acid-induced excitations. The results support an earlier conclusion that compounds reacting with the NMDA receptor do so in an extended configuration whereas the QUIS receptor has a more folded template. The possibility that QUIN reacts with a receptor different from those activated by other amino acids is considered. PMID- 2906297 TI - Behaviour of several enzymes of fetal chick intestine in tissue culture. AB - The behaviour of several enzymes is described of the fetal chick duodenum in tissue culture in a defined medium free of serum and hormones. During culture the activity of sucrase, maltase, alanine aminopeptidase, and gamma glutamyltransferase is raised in tissue explants, whereas the activity of other enzymes (dipeptidyl peptidase IV, leucine amino-peptidase, alkaline phosphatase) remains constant. After culture, depending on the enzyme, a varying amount of activity is found in the medium, a part of which can be sedimented by ultracentrifugation. Sucrase is subject to the strongest increase in activity during culture and thus should represent a sensitive marker for investigating maturation processes in the fetal intestine and their disturbances. PMID- 2906298 TI - Byciclic compounds with potential antiulcer and/or antisecretory activity. III--2 substituted tetrahydrothiazolo-[5,4-c]pyridines. AB - As the ultimate result of a long-term search for new bicyclic molecules potentially endowed with antiulcer and/or antisecretory activity, simple urea derivatives of 2-guanidino-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine [(VIII), Fig. 1; X = 0, R = alkyl], displaying a strong inhibition of stress- and ASA induced gastric ulcers and of basal gastric secretion, were found. Their potency does compare very favourably with that of cimetidine and ranitidine and approaches that of famotidine. On spontaneously beating guinea pig atria they behaved as inhibitors of the histamine H2-receptor. In contrast with cimetidine and ranitidine but like other recently described inhibitors (famotidine included), the most active compounds (VIII) caused a surmountable antagonism only at low concentrations and an unsurmountable antagonism at higher concentrations. The onset of action was slow, while the inhibitory effect was hardly reversed by washing. The rational development of the research and the synthetic approach, as well as a quantitative assessment of both in vitro and in vivo potencies in comparison with the best known, clinically used drugs, are shown in detail. PMID- 2906299 TI - Studies on the mechanism of salicylate-induced increase of insulin secretion in man. AB - Salicylate compounds are known to increase basal and stimulated insulin secretion in man. In our studies, infusion of lysine acetylsalicylate (72 mg/min) increased basal insulin levels and amplified insulin responses to glucose (5 g i.v.), arginine (5 g i.v.) and tolbutamide (1 g i.v.). Verapamil, an organic calcium antagonist, did not modify LAS-induced increase of basal insulin levels, but reduced the effect of LAS on glucose-induced insulin secretion. Calcitonin and somatostatin, two agents that inhibit basal and glucose-stimulated insulin secretion, inhibited the insulin response to glucose in presence of LAS infusion. The ability of salicylate compounds to augment insulin secretion might be due to multiple sites of action in the Beta-cells. PMID- 2906300 TI - Interaction of growth hormone-releasing factor and somatostatin on ulcer healing and mucosal growth in rats: role of gastrin and epidermal growth factor. AB - Growth hormone-releasing factor (GRF) was reported to possess the growth promoting action on the gastroduodenal mucosa that can be augmented by removal of endogenous somatostatin. Since mucosal proliferation was considered to contribute to healing of chronic gastroduodenal ulcerations, we designed the study to determine the interaction of GRF and somatostatin on the healing rate of acetic acid-induced chronic gastric and duodenal ulcers and on the growth of gastroduodenal mucosa in rats. GRF injected subcutaneously twice daily at 100 micrograms/kg/day for 7 days resulted in a significant enhancement of healing rate of both gastric and duodenal ulcerations and this was accompanied by a significant increase in the weight of the mucosa and the contents of RNA and DNA. GRF also significantly increased serum gastrin levels and the tissue contents of epidermal growth factor (EGF) in salivary glands, duodenum and pancreas, suggesting that both gastrin and EGF could contribute to mucosal trophic and ulcer healing effects of GRF. Somatostatin (100 micrograms/kg/day for 7 days) abolished almost completely the ulcer healing and mucosal growth-promoting effects of GRF and this was accompanied by the reduction in serum gastrin level and the tissue contents of EGF suggesting that the suppression of gastrin and EGF release could contribute to the observed effects of somatostatin. We conclude that GRF has both the ulcer healing and the mucosal trophic actions which can be antagonized by somatostatin and that gastrin and EGF may be implicated in these actions. PMID- 2906301 TI - Different effects of intraperitoneal or subcutaneous administration of H2 antagonists on pancreatic response to chronic administration of caerulein in rats. AB - This study deals with the effect of H2-receptor antagonists on pancreatic response to chronic administration of caerulein. Caerulein was administered alone or combined with cimetidine, ranitidine or famotidine twice a day in various regimes. At the end of treatment, pure pancreatic juice was collected after hormonal stimulation. Then, the rats were killed, and growth and composition of the pancreatic tissue were determined. Caerulein increased pancreatic weight and enzyme content as well as volume and enzyme activity of pancreatic juice. When given alone the three H2-receptor antagonists were totally ineffective. Both ranitidine and famotidine, but not cimetidine, significantly reduced pancreatic response to chronic administration of caerulein only when given intraperitoneally together with caerulein. On the contrary, separate applications of caerulein and ranitidine (or famotidine) did not influence caerulein-stimulated pancreatic growth or enzyme secretion. Moreover, in rats treated both intraperitoneally and subcutaneously with caerulein, the H2-antagonists reduced the pancreatic response only partially and in proportion to the intraperitoneal dose of caerulein. The responsiveness of pancreatic tissue to subcutaneous caerulein was not modified. The results suggest that H2-receptor antagonists induce (1) impaired uptake of caerulein when given together with peptide, but (2) have no specific inhibitory effect on pancreatic response to caerulein. PMID- 2906302 TI - [Diet and brain metabolism]. PMID- 2906303 TI - Effects of amino acid substitutions at the active site in Escherichia coli beta galactosidase. AB - Forty-nine amino acid substitutions were made at four positions in the Escherichia coli enzyme beta-galactosidase; three of the four targeted amino acids are thought to be part of the active site. Many of the substitutions were made by converting the appropriate codon in lacZ to an amber codon, and using one of 12 suppressor strains to introduce the replacement amino acid. Glu-461 and Tyr 503 were replaced, independently, with 13 amino acids. All 26 of the strains containing mutant enzymes are Lac-. Enzyme activity is reduced to less than 10% of wild type by substitutions at Glu-461 and to less than 1% of wild type by substitutions at Tyr-503. Many of the mutant enzymes have less than 0.1% wild type activity. His-464 and Met-3 were replaced with 11 and 12 amino acids, respectively. Strains containing any one of these mutant proteins are Lac+. The results support previous evidence that Glu-461 and Tyr-503 are essential for catalysis, and suggest that His-464 is not part of the active site. Site-directed mutagenesis was facilitated by construction of an f1 bacteriophage containing the complete lacZ gene on a single EcoRI fragment. PMID- 2906304 TI - Recombination within a subclass of restriction fragment length polymorphisms may help link classical and molecular genetics. AB - Restriction fragment length polymorphisms (RFLPs) are being used to construct complete linkage maps for many eukaryotic genomes. These RFLP maps can be used to predict the inheritance of important phenotypic loci and will assist in the molecular cloning of linked gene(s) which affect phenotypes of scientific, medical and agronomic importance. However, genetic linkage implies very little about the actual physical distances between loci. An assay is described which uses genetic recombinants to measure physical distance from a DNA probe to linked phenotypic loci. We have defined the subset of all RFLPs which have polymorphic restriction sites at both ends as class II RFLPs. The frequency of class II RFLPs is computed as a function of sequence divergence and total RFLP frequency for highly divergent genomes. Useful frequencies exist between organisms which differ by more than 7% in DNA sequence. Recombination within class II RFLPs will produce fragments of novel sizes which can be assayed by pulsed field electrophoresis to estimate physical distance in kilobase pairs between linked RFLP and phenotypic loci. This proposed assay should have particular applications to crop plants where highly divergent and polymorphic species are often genetically compatible and thus, where class II RFLPs will be most frequent. PMID- 2906305 TI - Chloroplast DNA diversity in populations of wild and cultivated barley. AB - Chloroplast DNA (cpDNA) diversity was found within and among populations (245 accessions total) of wild barley, Hordeum vulgare L. ssp. spontaneum Koch from Israel and Iran. Three polymorphic restriction sites (HindIII, EcoRI, BclI) which define three distinct cpDNA lineages were detected. One lineage is common to populations in the Hule Valley and Kinneret of northern Israel, and in Iran. The second lineage is found predominantly in the Lower Jordan Valley and Negev. The distribution of the third lineage is scattered but widespread throughout Israel. Sixty two accessions of cultivated barleys, H. vulgare L., were found, with two exceptions, to belong to just one cpDNA lineage of wild barley, indicating that the cpDNA of cultivated barley is less variable than its wild ancestor. These results demonstrate the need for assessing intraspecific cpDNA variability prior to choosing single accessions for phylogenetic constructions at the species level and higher. PMID- 2906306 TI - Maize glutamine synthetase cDNAs: isolation by direct genetic selection in Escherichia coli. AB - Maize glutamine synthetase cDNA clones were isolated by genetic selection for functional rescue of an Escherichia coli delta glnA mutant growing on medium lacking glutamine. The Black Mexican Sweet cDNA library used in this study was constructed in pUC13 such that cDNA sense strands were transcribed under the control of the lac promoter. E. coli delta glnA cells were transformed with cDNA library plasmid DNA, grown briefly in rich medium to allow phenotypic expression of the cDNAs and the pUC13 ampr gene, and challenged to grow on agar medium lacking glutamine. Large numbers of glutamine synthetase cDNA clones have been identified in individual 150-mm Petri dishes; all characterized cDNA clones carry complete coding sequences. Two cDNAs identical except for different 5' and 3' termini have been sequenced. The major open reading frame predicts a protein with an amino acid sequence that exhibits striking similarity to the amino acid sequences of the predicted products of previously sequenced eukaryotic glutamine synthetase cDNAs and genes. In addition, the maize glutamine synthetase cDNAs were shown to contain a 5' mini-ORF of 29 codons separated by 37 nucleotide pairs from the major ORF. This mini-ORF was shown not to be essential for the functional rescue of the E. coli delta glnA mutant. Expression of the cDNAs in E. coli is presumed to be due to the function of a polycistronic hybrid lac messenger RNA or translational fusions encoded by the pUC plasmids. Proteins of the expected sizes encoded by two different pUC clones were shown to react with antibodies to tobacco glutamine synthetase. PMID- 2906307 TI - Ribosomal gene structure, variation and inheritance in maize and its ancestors. AB - We have examined the structure of nuclear genes coding for ribosomal RNAs in maize and its wild relatives, the teosintes and Tripsacum. Digestion of the rDNA (genes coding for 18S, 5.8S and 26S RNAs) with 15 restriction endonucleases (with six base pair recognition sites) yields essentially a single map for the approximately 10,000 repeat units within an individual plant or species. Both length and site variation were detected among species and were concentrated in the intergenic spacer region of the rDNA repeat unit. This result is in agreement with patterns of rDNA change observed among wheat and its relatives (Triticeae), and among vertebrate species. Digestion of these nuclear DNAs with BamHI and subsequent hybridization with a 5S RNA gene-specific probe allowed determination of the size of the 5S gene repeat unit in maize, teosintes, and Tripsacum. Groupings in the genus Zea were characterized by distinct repeat unit types five Tripsacum species examined shared a 260 base pair major repeat unit type. Additionally, several other restriction endonuclease cleavage patterns differentiated among the 5S DNAs within the genus Zea. The rDNA and 5S DNA restriction site variation among the species can be interpreted phylogenetically and agrees with biochemical, karyotypic, and morphological evidence that places maize closest to the Mexican teosintes. For both gene arrays, contributions from each parental genome can be detected by restriction enzyme analysis of progeny from crosses between maize and two distantly related teosintes, Zea luxurians or Zea diploperennis, but certain teosinte arrays were underrepresented in some of the hybrids. PMID- 2906308 TI - Comparison of non-mutant and mutant waxy genes in rice and maize. AB - The waxy gene, which is responsible for the synthesis of amylose in endosperm and pollen, is genetically well characterized in many grasses including maize and rice. Homology between the previously cloned maize waxy gene and the rice gene has facilitated our cloning of a 15-kb HindIII fragment that contains the entire rice gene. A comparison of the restriction maps of the maize and rice genes indicates that many restriction sites within translated exons are conserved. In addition, the rice gene encodes a 2.4-kb transcript that programs the in vitro synthesis of a 64-kD pre-protein which is efficiently precipitated with maize waxy antisera. We demonstrate that these gene products are altered in rice strains containing mutant waxy genes. Southern blot analysis of 16 rice strains, ten containing waxy mutations, reveals that the waxy gene and flanking restriction fragments are virtually identical. These results contrast dramatically with the high level of insertions and deletions associated with restriction fragment length polymorphism and spontaneous mutations among the waxy alleles of maize. PMID- 2906309 TI - Genetic analysis of the fungus, Bremia lactucae, using restriction fragment length polymorphisms. AB - Restriction fragment length polymorphisms (RFLPs) were developed as genetic markers for Bremia lactucae, the biotrophic Oomycete fungus which causes lettuce downy mildew. By using 55 genomic and cDNA probes, a total of 61 RFLP loci were identified among three heterothallic isolates of B. lactucae. Of these 61 RFLP loci, 53 were heterozygous in at least one of the three strains and thus were informative for linkage analysis in at least one of two F1 crosses that were performed. Analysis of the cosegregation of these 53 RFLPs, eight avirulence loci and the mating type locus allowed the construction of a preliminary genetic linkage map consisting of 13 small linkage groups. Based on the extent of linkage detected among probes, the genome of B. lactucae can be estimated to be approximately 2000 cM. Linkage was detected between a RFLP locus and an avirulence gene, providing a potential starting point for chromosome walking to clone an avirulence gene. The high frequency of DNA polymorphism in naturally occurring isolates and the proper Mendelian segregation of loci detected by low copy number probes indicates that it will be possible to construct a detailed genetic map of B. lactucae using RFLPs as markers. The method of analysis employed here should be applicable to many other outbreeding, heterozygous species for which defined inbred lines are not available. PMID- 2906310 TI - Cloning and nucleotide sequence of the Streptomyces coelicolor gene encoding glutamine synthetase. AB - The Streptomyces coelicolor glutamine synthetase (GS) structural gene (glnA) was cloned by complementing the glutamine growth requirement of an Escherichia coli strain containing a deletion of its glnALG operon. Expression of the cloned S. coelicolor glnA gene in E. coli cells was found to require an E. coli plasmid promoter. The nucleotide sequence of an S. coelicolor 2280-bp DNA segment containing the glnA gene was determined and the complete glnA amino acid sequence deduced. Comparison of the derived S. coelicolor GS protein sequence with the amino acid sequences of GS from other bacteria suggests that the S. coelicolor GS protein is more similar to the GS proteins from Gram-negative bacteria than it is with the GS proteins from two Gram-positive bacteria, Bacillus subtilis and Clostridium acetobutylicum. PMID- 2906311 TI - Sequence of the Bacillus subtilis glutamine synthetase gene region. AB - The nucleotide sequence of the glutamine synthetase (GS) region of Bacillus subtilis has been determined and found to contain several unique features. An open reading frame (ORF) upstream of the GS structural gene is part of the same operon as GS and is involved in regulation. Two downstream ORFs are separated from glnA by an apparent Rho-independent termination site. One of the downstream ORFs encodes a very hydrophobic polypeptide and contains its own potential RNA polymerase and ribosome-binding sites. The derived amino acid (aa) sequence of B. subtilis GS is similar to that of several other prokaryotes, especially to the GS of Clostridium acetobutylicum. The B. subtilis and C. acetobutylicum enzymes differ from the others in the lack of a stretch of about 25 aa as well as the presence of extra cysteine residues in a region known to contain regulatory as well as catalytic mutations. The region around the tyrosine residue that is adenylylated in GS from many species is fairly similar in the B. subtilis GS despite its lack of adenylylation. PMID- 2906312 TI - Structural homology between virulence-associated bacterial adenylate cyclases. AB - The primary structure of the calmodulin-sensitive adenylate cyclase toxin from Bacillus anthracis has been determined from the corresponding nucleotide sequence and compared to that of the homologous toxin secreted by Bordetella pertussis. The cya gene of Bacillus anthracis encodes an 800 amino acid (aa) protein beginning with an N-terminal signal peptide. The central part of the B. anthracis adenylate cyclase includes a region of striking homology with the N-terminal part of the B. pertussis enzyme. In this region a particularly well conserved 24-aa peptide and two other less homologous peptides have been identified. These data corroborate the immunological relatedness of the two enzymes and suggest that the two prokaryotic calmodulin-sensitive adenylate cyclases originate from a common ancestor. PMID- 2906313 TI - Studies on locus expansion, library representation, and chromosome walking using an efficient method to screen cosmid libraries. AB - We have developed an efficient screening method to search for clones in cosmid libraries prepared from human genomic DNA. Genomic, cDNA, and cosmid probes have been used to isolate homologous cosmids from human chromosomes 7, 10, 16, 17 and X as part of a search for polymorphic nucleotide sequences. This method has been successfully applied to chromosome walking experiments at the interstitial retinol-binding protein locus on chromosome 10, and may be a useful tool for investigating representation of cloned sequences in cosmid libraries. Our library was prepared in the vector c2RB (Bates and Swift, 1983), but the method is applicable to any cosmid cloning system in which the inserted DNA can be separated from the vector by restriction enzyme digestion. A cosmid library containing five human genome equivalents can be rapidly screened using three to four Southern hybridization filters. This results in substantial labor saving, particularly when screening genomes of high complexity with many different probes. Another advantage of the system is that it allows for the long-term storage of the cosmids so that they can be screened whenever necessary. As a consequence, cosmid screening can be made a routine laboratory procedure. PMID- 2906314 TI - Sequence of mdr3 cDNA encoding a human P-glycoprotein. AB - We have determined the sequence of the human mdr3 gene using cDNA derived from liver RNA. The mdr3 gene codes for a member of a family of membrane proteins, the P-glycoproteins, overproduced in many multi-drug-resistant (MDR) cell lines. Like its relatives, the protein encoded by mdr3 has a deduced Mr of 140,000, which is presumably increased by glycosylation after synthesis. The sequence consists of two similar halves, each with a series of six hydrophobic segments that may form a membrane channel. The halves also possess nucleotide-binding consensus sequences, which presumably act as ATPases and drive drug transport. The presumed ATPase domains are all but identical to those of the human mdr1 gene product [Chen et al., Cell 47 (1986) 381-389]. We attribute this high level of sequence conservation to the repeated gene conversion that is evident from segments in which mdr1 and mdr3 differ only in a few silent mutations. Divergence between P glycoprotein family members is greatest at the N terminus and in the 60 amino acid linker connecting the two halves. In the putative trans-membrane domains approx. 80% of the amino acids are conserved between the products of mdr1 and mdr3. Although the function of mdr3 is not yet known, its high homology with mdr1 suggests that it also encodes an efflux pump with broad specificity. PMID- 2906315 TI - [Effects of prazosin, SGB-1534, dobutamine and isoproterenol on congestive heart failure in dogs]. AB - Effects of prazosin, dobutamine, isoproterenol and SGB-1534, a new alpha blockade, on congestive heart failure (CHF) in dogs were investigated. The model was made by protease injection into the left ventricular free wall, saline loading, and dextran and methoxamine infusions. By this maneuver, left atrial pressure (LAP), systemic vascular resistance (SVR) and left ventricular end diastolic pressure (LVEDP) were markedly increased, aortic blood flow (AoBF) was decreased, and systemic blood pressure was unchanged. In this model, the intravenous administration of prazosin (0.1 approximately 10.0 micrograms/kg, i.v.) increased AoBF and decreased LAP in a dose-dependent manner. The improvement of the CHF by prazosin was considered to result from its vasodilating action. SGB-1534 (0.1 approximately 10.0 micrograms/kg, i.v.) improved the CHF mainly through its vasodilating and positive inotropic actions, which is because SGB-1534 decreased SVR and increased Vmax. The magnitudes of vasodilation by SGB 1534 was greater than those by prazosin. These data indicate that SGB-1534 is useful in the treatment of CHF. Both dobutamine (5 approximately 100 micrograms/kg, i.v.) and isoproterenol (0.001 approximately 0.1 micrograms/kg, i.v.) improved the CHF through their vasodilating and positive inotropic actions in the canine CHF. The ratio of positive inotropism/vasodilation was greater for dobutamine than isoproterenol. The vasoconstriction by the large dose of dobutamine might participate in this difference between dobutamine and isoproterenol. PMID- 2906316 TI - [Antiallergic effects of mequitazine. 2. In vivo experiments]. AB - Antiallergic effects of mequitazine were investigated in vivo and compared with those of ketotifen and disodium cromoglycate (DSCG). The results obtained were as follows: 1) Mequitazine in doses of 2 and 5 mg/kg given, p.o., 1 hr prior to antigen challenge inhibited dose-dependently the 48-hr passive cutaneous anaphylaxis in rats. Five mg/kg of mequitazine showed almost the same extent of inhibitory activity as that of 1 mg/kg of ketotifen. An i.v. administration of 1 mg/kg DSCG 1 min before antigen challenge also showed a marked inhibition. 2) The experimental asthma induced by challenge with an i.v. injection of antigen in passively sensitized guinea pigs was fairly inhibited by the pretreatment with 5 mg/kg of mequitazine administered p.o., although 2 mg/kg of this drug showed only a slight inhibition. 3) The experimental asthma induced by aerosolized antigen was also fairly inhibited by the pretreatment with 5 mg/kg of mequitazine given p.o. PMID- 2906317 TI - Propranolol as a primary treatment of neuroleptic-induced akathisia. AB - We conducted a randomized, double-blind clinical trial of propranolol versus placebo as a single treatment of neuroleptic-induced akathisia in eleven schizophrenic patients. Neither propranolol nor placebo treated patients showed a significant improvement in akathisia. While propranolol may be useful as an adjunct to anticholinergic medication in the treatment of neuroleptic-induced akathisia, propranolol does not appear to be effective within 48 hours as a primary treatment in a select group of schizophrenic patients. PMID- 2906318 TI - Treatment of the agitated demented elderly patient. PMID- 2906319 TI - Recent advances in the psychopharmacological treatment of anxiety disorders. AB - The authors review recent progress in the pharmacological treatment of anxiety disorders. Most research within the last five years has focused on panic disorder; the findings include support for the usefulness of imipramine and clomipramine and probably other agents; evidence that the benzodiazepines alprazolam, diazepam, lorazepam, and clonazepam are approximately equally effective as antipanic agents; and high variability in relapse rates after discontinuation of drug treatment. Further work is required to determine whether buspirone and other forthcoming serotonin agonist drugs have a role in treating panic disorder and other anxiety disorders. For generalized anxiety disorder, scientific studies do not support the effectiveness of beta blocker; tricyclics may be potentially useful. Psychopharmacological treatments for social phobia, obsessive-compulsive disorder, and posttraumatic stress disorder are also reviewed. PMID- 2906320 TI - How to examine patients using the Abnormal Involuntary Movement Scale. AB - The Abnormal Involuntary Movement Scale (AIMS) examination has been widely recommended for periodic screening for tardive dyskinesia and follow-up of patients diagnosed with the disorder. However, few guidelines exist about how to use the examination in clinical practice. The authors discuss for whom, when, and how the AIMS examination can be used in a multidisciplinary setting; amplify the original instructions for the examination; and propose conventions to clarify scoring. Noting that the AIMS examination is not specific for tardive dyskinesia, they discuss a clinical approach to the patient who is found to have abnormal movements. The AIMS examination is best conducted within the context of an ongoing treatment program, the authors say, and should be part of the informed consent process necessary with patients treated with neuroleptic drugs. PMID- 2906321 TI - Neuroleptic dose reduction for schizophrenic outpatients: a three-year follow-up study. PMID- 2906322 TI - Localization of the FGR protooncogene on the genetic linkage map of human chromosome 1p. AB - A restriction fragment length polymorphism (RFLP) at the human FGR gene, a member of the src family of protooncogenes, has been identified and used to locate FGR on the genetic linkage map of human chromosome 1p. Single-copy sequences subcloned from a cosmid containing the human FGR gene were used to screen a panel of genomic DNAs for RFLPs. One plasmid, designated pB8, detected a high-frequency EcoRI RFLP (allele frequencies, 0.57/0.43). Analysis of a panel of somatic cell hybrids demonstrated that pB8 maps to the region 1p31-pter. Genetic linkage analysis of the 40 families provided by the Centre d'Etude du Polymorphisme Humain (CEPH) showed that FGR maps to a location 3.1 cM from the Rh blood group locus (RH), and falls in the 17.5-cM gap between alpha-fucosidase (FUCA1) and D1S57. The relative gene order of RH and FGR could not be determined unequivocally, but the most favored gene order was 1pter-PND-ALPL-FUCA1-FGR-RH D1S57-MYCL. PMID- 2906323 TI - Genetic linkage map of human chromosome 21. AB - Two of the most common disorders affecting the human nervous system, Down syndrome and Alzheimer's disease, involve genes residing on human chromosome 21. A genetic linkage map of human chromosome 21 has been constructed using 13 anonymous DNA markers and cDNAs encoding the genes for superoxide dismutase 1 (SOD1) and the precursor of Alzheimer's amyloid beta peptide (APP). Segregation of restriction fragment length polymorphisms (RFLPs) for these genes and DNA markers was traced in a large Venezuelan kindred established as a "reference" pedigree for human linkage analysis. The 15 loci form a single linkage group spanning 81 cM on the long arm of chromosome 21, with a markedly increased frequency of recombination occurring toward the telomere. Consequently, 40% of the genetic length of the long arm corresponds to less than 10% of its cytogenetic length, represented by the terminal half of 21q22.3. Females displayed greater recombination than males throughout the linkage group, with the difference being most striking for markers just below the centromere. Definition of the linkage relationships for these chromosome 21 markers will help refine the map position of the familial Alzheimer's disease gene and facilitate investigation of the role of recombination in nondisjunction associated with Down syndrome. PMID- 2906324 TI - Construction of a chromosome 15-specific linking library and identification of potential gene sequences. AB - We have tested a strategy for the construction of a total restriction fragment map of a human chromosome and the rapid isolation of a great number of genes from a specific chromosome. The strategy is based on the cloning of chromosome specific CpG-rich DNA sequences which are present at the 5' end of many genes. This approach has two important implications: (i) the clones can be used to probe pulsed-field gradient gel blots and link restriction fragments generated by CpG restriction endonucleases, and (ii) the finding of tight genetic or physical linkage between one of these gene probes and a given hereditary disease would make the marker a good candidate gene for this disease. We have constructed a chromosome 15-specific linking library and identified potential gene sequences. PMID- 2906325 TI - Regional localization of the autosomal dominant polycystic kidney disease locus. AB - The localization of the autosomal dominant polycystic kidney disease locus (PKD1) within an array of anonymous polymorphic DNA sequences on chromosome 16 band p13 was determined by multipoint mapping. Nine polymorphic DNA markers, including two hypervariable sequences, were used to study 19 PKD1 and 21 reference families. PKD1 was found to lie proximal to the 3' and 5' hypervariable regions of alpha globin and distal to the anonymous sequence CRI-0327. Somatic cell hybrid mapping places PKD1 within the region 16p13.11-16pter. The availability of an array of linked markers which bracket the PKD1 locus provides a framework for further attempts to identify the PKD1 gene and offers an improved method of presymptomatic diagnosis of the disease. PMID- 2906327 TI - Multilocus molecular mapping of the mouse X chromosome. AB - Using restriction fragment length polymorphisms (RFLPs) and enzymatic variants between distantly related mouse species, we have assigned three genes to the mouse X chromosome and concurrently mapped a total of eight genes spanning an estimated 50 cM of the chromosome. Segregation of RFLPs in over 200 male progeny from interspecies backcrosses between the inbred strain C57BL/6JRos and either wild-derived Mus musculus or Mus spretus was followed for the murine genes Timp (tissue inhibitor of metalloproteinases), Cf-8 (coagulation factor VIII), and Rsvp (red-sensitive visual pigment) and the known X-linked markers Otc, Hprt, Cf 9, G6pd, and Ags. From the centromere, the gene order was defined as Otc, Timp, Hprt, Cf-9, (Cf-8/Rsvp/G6pd), Ags, by minimizing the number of multiple recombinational events. No significant differences in map order or frequency of recombination were observed between the two backcross series studied. The use of Southern analysis has allowed us to add new genes to the map in a cumulative manner, and as probes become available, additional markers can be mapped, using the same set of mice, by utilizing existing blots or resampling the DNAs. The use of probes for functional genes has allowed us to directly compare the X chromosomes of mouse and man and has provided insight into chromosomal rearrangements which have occurred during the evolutionary divergence of these species, as well as to define the extent of linkage homologies. PMID- 2906326 TI - Two thyroid hormone regulated genes, the beta-subunits of nerve growth factor (NGFB) and thyroid stimulating hormone (TSHB), are located less than 310 kb apart in both human and mouse genomes. AB - Two thyroid hormone regulated genes, the beta-subunits of nerve growth factor (NGFB) and thyroid stimulating hormone (TSHB), have been assigned to mouse chromosome 3 and human chromosome 1p22. We have used the techniques of linkage analysis and pulsed field gel electrophoresis to determine the proximity of these two antithetically regulated genes in this conserved linkage group. Four novel restriction fragment length polymorphisms were identified at the human TSHB gene. Two-point linkage analysis between TSHB and NGFB in 46 families, including the Centre d'Etude du Polymorphisme Humain (CEPH) reference panel, demonstrated no recombination (theta = 0.00, Z = 42.8). Analysis of this region by pulsed field gel electrophoresis showed that the genes for TSHB and NGFB are located less than 310 kb apart in man and 220 kb in the mouse. PMID- 2906328 TI - Gene organization of murine homeobox-containing gene clusters. AB - A chromosomal walk which links a previously described and a new homeobox to the Hox-2 murine homeobox gene cluster is described, and the nucleotide sequence of the new homeobox is presented. With these new data the Hox-2 gene cluster contains seven loci on an approximately 100-kb-long physical map. Homology comparisons reveal that a significant number of vertebrate homeoboxes are in fact analogous. We also find that the linear order of homologous homeoboxes is similar in the two murine gene complexes, Hox-1 and Hox-2, and among the human homeobox loci on chromosome 17. Conservation of the homeo-domain and the linear gene order of homeobox-containing genes in vertebrates is discussed in light of the interactions and the anteroposterior linear order of homeotic loci in insects. PMID- 2906329 TI - Partial digestion with restriction enzymes of ultraviolet-irradiated human genomic DNA: a method for identifying restriction site polymorphisms. AB - A method for partial digestion of total human DNA with restriction enzymes has been developed on the basis of a principle already utilized by P.A. Whittaker and E. Southern (1986, Gene 41: 129-134) for the analysis of phage lambda recombinants. Total human DNA irradiated with uv light of 254 nm is partially digested by restriction enzymes that recognize sequences containing adjacent thymidines because of TT dimer formation. The products resulting from partial digestion of specific genomic regions are detected in Southern blots by genomic unique DNA probes with high reproducibility. This procedure is rapid and simple to perform because the same conditions of uv irradiation are used for different enzymes and probes. It is shown that restriction site polymorphisms occurring in the genomic regions analyzed are recognized by the "allelic" partial digest patterns they determine. PMID- 2906330 TI - Drug therapy in childhood hypertension. PMID- 2906331 TI - Effects of acidic and basic fibroblast growth factors (aFGF and bFGF) on the proliferation and the glutamine synthetase expression of rat astroblasts in culture. AB - The two fibroblast growth factors called acidic and basic FGF (aFGF and bFGF) show a strong homology (55%) of their amino acid sequence (Esch et al.: Proc. Nat. Acad. Sci. USA 85:6507-6511, 1985). The effects of these factors on the rate of proliferation of rat astroblasts and on the expression of glutamine synthetase activity in cells grown in primary culture were investigated and compared under various culture conditions. In all the experimental conditions used, both growth factors triggered the proliferation of the cells to the same extent and with similar dose dependence. The mitogenic activities of aFGF and bFGF were potentiated similarly by heparan sulfate and by heparin, with a maximum stimulation of about 100% at 100 micrograms/ml heparin. Treatment of the cells with either of the two factors resulted in identical enhancement of the activity of glutamine synthetase relative to total proteins. These results suggest that both factors act either through the same membrane receptors or through different receptors that mediate nearly identical effects. PMID- 2906332 TI - Alcoholism: scientific basis of a neuropsychogenetic disease. AB - Until recently alcoholism was regarded as being an incurable psychological problem. During the last decade a chain of research has led to a new insight into the causes and potential alleviation of alcohol craving: Recent discoveries indicate that the brain has receptor sites for naturally occurring opiate-like substances (endorphins and enkephalins) which are produced by the nervous system. Opiates such as morphine or heroin, and some of the metabolic products of alcohol (tetrahydroisoquinolines), can also attach themselves to these receptors. It has been further discovered that the craving for alcohol is related to a deficiency of the naturally occurring opiate-like substances as well as other neurotransmitter substances. This deficiency can occur genetically or as a result of prolonged stress or long-term heavy drinking. The neurochemical imbalance may be treated chemically, leading to a possible alleviation of the craving for alcohol, especially in conjunction with psychotherapeutic and counseling regimens. PMID- 2906333 TI - Serological evidence of hantavirus infection in laboratory rats and personnel. AB - Laboratory-acquired haemorrhagic fever with renal syndrome (HFRS) has been reported in many countries. A serological survey of laboratory white rats and of laboratory personnel for antibodies to hantaviruses was conducted in Singapore. Forty-four per cent (143/329) of rats were seropositive by the indirect immunofluorescent antibody test but none had hantaviral antigens in lung tissues. Two of 74 laboratory personnel were seropositive but neither had a history of clinical illness. The high seropositivity rate among laboratory rats led to their replacement with Hantaan virus-free strains. To eliminate the hazard of laboratory-acquired HFRS, regular serological screening of laboratory rats and replacement of infected animals with seronegative stocks should be implemented. High risk techniques with laboratory rats, which are likely to generate aerosols, should be performed in biological safety cabinets. Serological surveillance of laboratory personnel and reporting of suspected HFRS cases are useful in the early detection of hantavirus infection. PMID- 2906334 TI - Estrogen replacement therapy. Symposium proceedings. San Francisco, California, April 1985. PMID- 2906335 TI - Preventing postmenopausal osteoporosis with estrogen replacement therapy. PMID- 2906336 TI - Metabolism of oral estrogen. PMID- 2906337 TI - Estrogen replacement therapy for atrophic vaginitis. PMID- 2906338 TI - Estrone v estradiol: an examination of relative carcinogenic potential. PMID- 2906339 TI - Safety and efficacy of Estrace (micronized 17 beta-estradiol). PMID- 2906340 TI - Clinical application of estrogen replacement therapy. PMID- 2906341 TI - Estrogen replacement therapy: an overview. PMID- 2906342 TI - Gestodene: an advance in low-dose contraception. Symposium proceedings. Singapore, October 1986. PMID- 2906343 TI - Metabolic effects of two low-dose triphasic oral contraceptives containing ethinyl estradiol and levonorgestrel or gestodene. AB - A well-known triphasic oral contraceptive (OC) containing ethinyl estradiol (EE) plus levonorgestrel (LNG) was compared with a triphasic containing the same dose of EE in combination with a 14% smaller dose of a new progestogen gestodene (GTD), in a prospective study of 24 and 20 healthy young women, respectively. Serial determinations of lipids, lipoproteins, and carrier proteins, and repeated standardized oral glucose tolerance tests (OGTTs) were conducted during 12 months of OC use. All lipid concentrations recorded before and during both treatments were strictly within the normal range. After 12 months, no significant fluctuations were observed in levels of total cholesterol, HDL-cholesterol, LDL cholesterol, VLDL-cholesterol, and apolipoprotein A1; concentrations of total triglycerides, phospholipids, and apolipoprotein B were slightly but significantly increased; the epidemiologically important ratios of HDL cholesterol:total cholesterol and apolipoprotein A1:apolipoprotein B were not significantly changed, while the ratio of LDL-cholesterol:HDL-cholesterol was significantly decreased at 12 months of use of the GTD triphasic. SHBG levels (+ 100% over basal during use of the LNG-OC and + 200% with the GTD-OC) and transcortin (+ 100% over basal) increased early and remained stable. During use of the LNG-OC, glucose tolerance was strictly unchanged, while insulin response to a 75-g glucose load was transiently increased at 6 months (area under the curve [AUC] + 29%) before returning to normal at 12 months. During GTD-OC treatment, glucose tolerance was slightly impaired (AUC + 14%) at 6 months but back to normal at 12 months, while insulin response during OGTT was completely unaltered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2906344 TI - Blood coagulation with a combination pill containing gestodene and ethinyl estradiol. AB - The coagulation effects of oral contraceptives are determined by the interaction of the estrogen and the progestogen components. Serial studies on the coagulation system were carried out in 120 randomly allocated healthy women to compare the effects of (1) triphasic gestodene/ethinyl estradiol and triphasic levonorgestrel/ethinyl estradiol and (2) monophasic gestodene/ethinyl estradiol and monophasic desogestrel/ethinyl estradiol. The triphasic study showed significant increases in factor VII, factor X, fibrinogen, plasminogen, and fibrinolytic activity. No significant differences were noted between levonorgestrel and gestodene except for factor VII, which was higher with gestodene. Antithrombin III and anti-Xa were unchanged, and platelet aggregation was slightly accelerated with gestodene. The monophasic study is still in progress: Significant increases of factor VII, factor X, plasminogen, and fibrinolytic activity and no changes in antithrombin III, anti-Xa, and platelet aggregation have been found with both monophasic gestodene and desogestrel. The results of the triphasic study indicate that the effect of gestodene on the blood coagulation system is similar to that of levonorgestrel and that both formulations increase fibrinolytic activity. The increased coagulation activity would appear to be counteracted by enhanced fibrinolysis, so protecting the dynamic balance between coagulation and fibrinolysis. Further data are required in the monophasic gestodene and desogestrel study before any conclusions can be drawn. PMID- 2906346 TI - Oral contraception with a triphasic combination of gestodene and ethinyl estradiol: results of a multicenter clinical study. AB - The clinical effects of a low-dose triphasic oral contraceptive containing the new progestogen gestodene and ethinyl estradiol were investigated in phase II and III multicenter studies. The phase II study compared the clinical effects in 377 women taking this new compound during 2123 cycles with the effects of a low-dose triphasic combination of levonorgestrel and ethinyl estradiol in 362 women treated in 2088 cycles. The discontinuation rates after 6 months were similar in the two groups, and no major differences in side effects were observed. Cycle control was better during intake of the gestodene-containing preparation, since spotting occurred less frequently (P less than .05). The phase III investigation comprised 1921 women representing a total of 27,308 cycles. The Pearl index was 0.05. During the 24-month trial, 243 women (12.7%) dropped out of the study because of side effects, mainly bleeding disturbances (6.0%), headache (2.2%), and breast tension (2.0%). The results of these studies indicate that the triphasic combination of gestodene and ethinyl estradiol is well tolerated and provides high contraceptive efficacy and good cycle control. PMID- 2906345 TI - Clinical and metabolic effects of gestodene and levonorgestrel. AB - The new low-dose combination oral contraceptive (OC) containing 75 micrograms of the new progestogen gestodene (GTD) plus 30 micrograms ethinyl estradiol (EE) was clinically tested and compared with a levonorgestrel (LNG) combined pill (150 micrograms LNG plus 30 micrograms EE). In a randomized clinical comparative study (A), 176 women were treated with the GTD-containing pill and 185 with the LNG containing pill for six cycles. This study was followed by a second multicenter study (B) covering 707 patients taking the GTD-containing pill for up to 24 cycles (total, 9,947 cycles). In a third study (C), metabolic effects were assessed using a randomly organized baseline control trial (pretreatment/treatment cycles); 30 patients received the GTD-containing pill and 30 received the LNG-containing pill. Carbohydrate metabolism, lipid metabolism, and blood clotting were investigated, and an interim analysis was performed after six OC cycles. No pregnancies and no severe side effects occurred in any of the studies. Intermenstrual bleeding decreased as usual during treatment. In the total number of gestodene cycles in studies A and B, there was a 6.9% incidence of spotting, a 0.8% incidence of breakthrough bleeding, and a 0.7% incidence of both spotting and breakthrough bleeding in studies A and B patients taking gestodene. Amenorrhea occurred in 0.6% of cycles. Body weight remained unchanged (+/- 2 kg) after 24 cycles in 80.5% of study B patients taking gestodene. Blood pressure remained normal in about 95% of all study B patients; a normalization was observed in greater than 60% of patients with previously elevated blood pressure. No clinically relevant changes in carbohydrate metabolism, lipid metabolism, or blood clotting were observed in study C. The new GTD-containing low-dose combination pill proved to be a safe and reliable contraceptive agent. PMID- 2906347 TI - Pharmacological and endocrine profiles of gestodene. AB - Efforts to minimize oral contraceptive side effects have focused on the use of new dosage schemes and the synthesis of new steroids that can be used in safer, low-dose formulations. To determine whether the new progestogen gestodene offers an advantage in this regard, we studied its pharmacological and endocrine profiles. Gestodene was found to exhibit relative binding affinity and biological activity profiles similar to or better than those of progestogens in current use. Modulation by gestodene of luteinizing hormone-releasing hormone (LH-RH) stimulated gonadotropin release in vitro and in vivo in a rat model system indicated that gestodene is some three times as biologically active as levonorgestrel. The borderline dose for inhibition of ovulation by gestodene was estimated in a total of 23 women with normal cycles. Levels of LH-RH, follicle stimulating hormone, 17 beta-estradiol, and progesterone were estimated during the ingestion of various doses of gestodene. A dose of 30 micrograms of gestodene caused inhibition of ovulation in 11 out of 12 subjects, and eight out of 11 showed follicular maturation. When 40 micrograms of gestodene was taken, six out of seven women did not ovulate, and one out of seven had a cycle with luteal insufficiency. These data indicate that 40 micrograms of gestodene is the borderline dose for inhibition of ovulation. A combination of 75 micrograms gestodene with 30 micrograms ethinyl estradiol was found to inhibit ovulation in ten subjects, and no follicular maturation was noted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2906349 TI - Vincristine-resistant human cancer KB cell line and increased expression of multidrug-resistance gene. AB - A multidrug-resistant clone of human cancer KB cells was isolated by stepwise selection on exposure to increasing doses of vincristine. The final clone, VJ 300, obtained after ethylmethane sulfonate mutagenesis showed 400-fold higher resistance to vincristine than did KB cells. Cellular accumulation of vincristine in VJ-300 was decreased to less than one-tenth of that in KB. The cells were also cross-resistant to daunomycin, adriamycin, actinomycin D, colchicine and VP-16. During continuous culturing in the absence of any drug for several months, a different colchicine-resistant and multidrug-resistant clone, KB-C1, reverted almost completely to drug sensitivity, whereas drug resistance in VJ-300 was stably maintained. Amplification of the multidrug-resistance-1 (mdr-1) gene was more than 20-fold in KB-C1, but less than 2-fold in VJ-300. mdr-1 mRNA was, however, expressed in VJ-300 at a rate comparable to KB-C1. Acquisition of high multidrug resistance in VJ-300 might be correlated with both activated transcription of mdr-1 gene and amplification. PMID- 2906348 TI - The ageing brain, neuroleptic drugs and the enigma of schizophrenia. PMID- 2906350 TI - Use of osmotic pumps for subcutaneous infusion of growth hormone-releasing factors in steers and wethers. AB - Osmotic pumps were evaluated for 7-d delivery of growth hormone-releasing factor (GRF). In Exp. 1, 12 steers weighing 253 kg received hGRF(1-29)NH2 in H2O at rates of 0, 3, 30 and 300 pmol.h-1.kg-1. Pumps were implanted s.c. on d 0 and removed at 1200 on d 7. Blood samples were drawn at 20-min intervals from 0800 to 1200 on d -1, 1, 3, 5, 7 and 9. Growth hormone levels were not altered by GRF treatment (P greater than .05). Solubility and volume limitations render hGRF(1 29)NH2 delivery via osmotic pumps problematical. Flow rate and duration of release of dimethyl sulfoxide (DMSO):H2) (1:1) from osmotic pumps incubated in vivo and in vitro were found to be consistent with manufacturer's specifications. Two hGRF(1-29) analogues, Ro23-7863 and 4SG-29, were dissolved in DMSO:H2O. In Exp. 2, six 222-kg steers had pumps implanted and blood samples were taken as in Exp. 1. Three steers received each analogue at a rate of 300 pmol.h-1.kg-1. Analogues had similar GH-releasing ability and GH levels differed (P less than 0.001) among days, being approximately fourfold higher on d 3, 5 and 7 than on d 1, 1 and 9. Residual analogue solutions retained full bioactivity after 7-d implantation, and in vitro biopotencies of Ro23-7863 and 4SG-29 were similar (Exp. 3). In Exp. 4, 15 wethers (means = 31.3 kg) received osmotic pumps delivering 0, 3, 15, 75 and 300 pmol.h-1.kg-1 Ro23-7863 in DMSO:H2O for 7 d. Lambs were bled at 0800 and 1400 from d -1 to 8. The latter two doses increased (P less than .01) mean GH levels 2.7- and 4.3-fold over those in control animals during the treatment period. Results demonstrate that increased GH secretion can be elicited in steers and wethers for 1 wk by continuous s.c. infusion of GRF analogues utilizing osmotic pumps. PMID- 2906351 TI - Phenotypic analysis of mouse thymus development. PMID- 2906353 TI - [Autonomic functions in human T-lymphotropic virus type-I (HTLV-1) associated myelopathy]. PMID- 2906352 TI - Gamma delta antigen receptors of Thy-1+ dendritic epidermal cells: implications for thymic differentiation. PMID- 2906354 TI - [An autopsy case of glucagonoma associated with production of several hormones]. PMID- 2906355 TI - Computer simulation of management strategies for Psorophora columbiae in the rice agroecosystem. AB - Various control strategies were evaluated using a previously-described and validated (Focks et al. 1988a, 1988b) simulation model (PcSim) of the population dynamics of Psorophora columbiae breeding in the rice agroecosystem. As expected from field experience, focally-applied ground or aerial ULV aerosols of insecticides were seen to provide local control of peak populations. Similar control was predicted for larvicides when also used in and around urban and suburban areas. Both of these measures were predicted by simulation to provide only short term control of adults as a result of immigration of adults from surrounding, untreated provide only short term control of adults as a result of immigration of adults from surrounding, untreated areas. Evaluations of the effectiveness of diapause egg control or the elimination of early spring broods to provide lasting, season-long suppression were not encouraging if only conventional methods such as insecticides or tillage were used. This was primarily because the ability of Ps. columbiae to recolonize treated areas during the course of a breeding season would require the treatment of prohibitively large, parish- (i.e., county-) sized areas. Evaluations of host management (either removal or residual insecticide treatment of cattle) in and around urban and suburban areas were more encouraging. This technique, by providing continuing pressure on populations, has the potential to offset the impact of immigration and thereby afford long-term suppression in local areas. Finally, evaluations of the impact of modifications to irrigation practices indicated that this approach warrants consideration as a supplemental control technique. These results suggest that field evaluations of model predictions would be useful. They emphasize the need to better understand the movement and spatial distribution of Ps. columbiae. These factors would bear directly on the cost and therefore, the practicality of several of the long-term suppression strategies evaluated as they determine the size of the treatment area surrounding population centers needed to offset the impact of immigration from surrounding, untreated areas. PMID- 2906356 TI - Horse-baited insect trap and mobile insect sorting table used in a disease vector identification study. AB - A horse-baited trap and a mobile insect sorting table were used to conduct an arthropod survey for potential vectors of Potomac Horse Fever in southern Maryland and northern Virginia. The trap and table worked effectively for the live collection and sorting of haemophagous Diptera such as: Simulium spp., Stomoxys calcitrans, Musca autumnalis, Tabanus spp. and Chrysops spp. during the diurnal collections periods, and Culicoides spp. during the crepuscular periods. The trap was not as convenient for live collection of mosquito species during the nocturnal period. Modifications to the trap design was suggested for mosquito live trapping. PMID- 2906357 TI - Efficacy and longevity of Bacillus sphaericus 2362 formulations for control of mosquito larvae in dairy wastewater lagoons. AB - Bacillus sphaericus strain 2362 was evaluated for the control of Culex larvae in dairy wastewater lagoons. Both initial and long-term efficacy were studied. Two primary powder preparations of ABG-6184 yielded mediocre and short-term control at the rates of 0.25 and 0.5 lb/acre (0.26 and 0.56 kg/ha), while level of control and persistence greatly increased as the dosages were increased to 1.0, 2.0 and 4.0 lb/acre (1.12, 2.24 and 4.48 kg/ha). The 1.0 and 2.0 lb/acre rates yielded almost 100% control for 4 weeks and the 4.0 lb/acre rate yielded control (99%) for 49 days or longer. A flowable concentrate preparation (BSP-2) yielded complete initial and persistent control of larvae for 14-21 days at 2.0, 4.0 and 5.0 lb/acre (2.24, 4.49 and 5.6 kg/ha). Granular formulations of B. sphaericus 2362 (ABG-6185) were also evaluated at 2.5, 5.0, 7.5, 10.0 and 20.0 lb/acre (2.8, 5.6, 8.4, 11.2 and 22.4 kg/ha) of the granules. Some of the formulations were more active than the others, yielding excellent initial and persistent control (80% +) for 14-21 days with one treatment. PMID- 2906358 TI - An evaluation of Gambusia affinis and Bacillus thuringiensis var. israelensis as mosquito control agents in California wild rice fields. AB - The mosquito control potential of the mosquitofish and Bacillus thuringiensis var. israelensis (Bti) were evaluated in experimental wild rice fields in Lake County, California. Fields were assigned one of six treatment: control, 1.1 kg/ha G. affinis, 3.4 kg/ha G. affinis, Bti only (6 kg/ha Vectobac granules), 1.1 kg/ha G. affinis plus Bti and 3.4 kg/ha G. affinis plus Bti. Gambusia affinis, at both release rates, significantly reduced the mosquito population at densities exceeding 100 fish/minnow trap. Treatments with Bti significantly reduced larval population; however, the populations in the fields without fish rebounded to pretreatment levels within two weeks. In fields stocked with G. affinis and treated with Bti, populations remained low after Bti treatment. Nontarget populations of arthropods were significantly lower in fields stocked with G. affinis than in fields without fish on one or more sampling dates. PMID- 2906359 TI - Toxicity, localization and elimination of the phototoxin, alpha-terthienyl, in mosquito larvae. AB - Mosquito larvae were examined to determine interspecific and interstrain differences in susceptibility to the larvicidal effects of the plant-derived phototoxin, alpha-terthienyl (alpha-T). The LC50 values were as follows: Aedes aegypti, 4 ppb; Ae. epactius, 6 ppb; anopheles stephensi, 14 ppb; malathion susceptible Culex tarsalis (S), 12 ppb; malathion-resistant Cx. tarsalis (R), 16 ppb. Fluorescence studies indicated localization of alpha-T in the midgut epithelium and in the lumen of Malpighian tubules. Rates of elimination of tritiated alpha-T differed significantly between Ae. aegypti and Cx. tarsalis (S) larvae. Rate of 3H-alpha-T elimination was inversely correlated with susceptibility to the toxic effects of the compound. The toxicological significance of selective alpha-T accumulation and the importance of alpha-T elimination in determining sensitivity are discussed. PMID- 2906360 TI - Suburban accumulations of discarded tires in northeastern Illinois and their associated mosquitoes. AB - In response to a growing, human suburban population and an escalating problem of used tire disposal, a summer-long survey of discarded tires and their associated mosquitoes was conducted in northeastern Illinois in 1985. Within a 291 km2 area, a monthly average of 7,823 tires were distributed among 127 sources classified into 7 categories: fields/ditches (25% of total sources); salvage yards (7%); trucking/construction companies (13%); woodlots (15%); school playgrounds (11%); service stations (16%); and tire dealers (11%). Distribution and abundance of each source category appeared to reflect local land usage and extent of urbanization. Wooded sites surpassed service stations, dealers, and salvage yards in the average percentage of flooded tires (86% vs. 25% ea.) and percentage of those larval-infested (58% vs. 25% ea.). Overall, 6,398 mosquito larvae among 9 species were collected with Culex restuans (82%) and Cx. pipiens (13%) predominating. Species segregations with respect to the tire source are revealed. Possible control strategies of mosquitoes in tires are summarized. PMID- 2906361 TI - A method for dispensing planaria (Dugesia dorotocephala) for mosquito control. PMID- 2906362 TI - Granulomatous angiitis of the central nervous system: protean manifestations and response to treatment. AB - Granulomatous angiitis is an uncommon necrotising vasculitis of unknown cause restricted to vessels of the central nervous system. Five tissue-proven cases emphasise the protean manifestations of this disease and the difficulties encountered in reaching a diagnosis. One patient presented with a temporoparietal mass, the second, a progressive dementia, the third suggested herpes simplex encephalitis, the fourth mimicked multi-infarct state; and the fifth presented with a cerebellar mass lesion. In four cases with CSF examination, protein was elevated (81-193 gm/l) and three patients had mononuclear pleocytosis (12-800 WBC/mm3). Cerebral arteriogram suggested vasculitis in only one of four cases. Diagnosis was made by brain biopsy in three cases and all three were treated successfully. The diagnosis in the two other cases was made at postmortem examination. PMID- 2906363 TI - CSF gradients for amino acid neurotransmitters. AB - Amino acid concentrations were measured in CSF samples obtained by lumbar puncture in 51 patients, cervical puncture in 16 patients, spinal drains in nine patients, ventricular taps in five patients and from below a spinal block in six patients. There was evidence of a rostrocaudal gradient for GABA and taurine and a reverse gradient for alanine and asparagine. Lumbar CSF glycine concentrations rose with increasing age whilst GABA concentrations fell. Women had significantly lower concentrations of asparagine and glutamine and elevated taurine compared to men. The influence of biological factors and gradients must be taken into account before the interpretation of changes in CSF amino acid concentrations. PMID- 2906364 TI - A nursing process approach to epidural analgesia. AB - Epidural narcotics are finding increasing favor in management of postcesarean birth pain. Effective pain relief coupled with minimal side effects often make this technique the method of choice. To provide comprehensive and safe nursing care for the mother using epidural narcotics, nurses must be knowledgeable about the technique, drugs, and associated patient responses. Nursing management using a care plan with nursing diagnosis and expected patient outcomes will help nurses plan their care of these patients. PMID- 2906365 TI - Minimal internal and external fixation in oblique lower extremity fractures: a report of five cases and description of technique. AB - Interfragmentary lag screw internal fixation was combined with external fixation to treat five difficult oblique lower extremity fractures. Uncomplicated primary bone healing was achieved in all five cases in spite of crush injury, devascularization, or local infection. This method represents a treatment option for the difficult oblique fracture and reconfirms the role of fixation in fracture biology. PMID- 2906366 TI - Permissive role of calcium in alpha 1-adrenergic stimulation of pineal phosphatidylinositol phosphodiesterase (phospholipase C) activity. AB - Activation of alpha 1-adrenergic receptors increases [Ca+2]i and phosphatidylinositol phosphodiesterase (phospholipase C) activity in the pinealocyte. In this report the receptor involved in the stimulation of phospholipase C activity was further characterized, and the role of Ca2+ in this effect was investigated in some detail. Phospholipase C activity was estimated by measuring the production of [3H]inositol phosphates by [3H]inositol-labelled dispersed pinealocytes in suspension culture. Norepinephrine stimulated [3H]inositol monophosphate production severalfold; this was blocked by alpha 1 adrenergic antagonists, including prazosin, WB 4101, and phenoxybenzamine, but by neither an alpha 2- nor a beta-adrenergic antagonist, confirming that an alpha 1 adrenoceptor is involved in the regulation of phosphatidylinositol hydrolysis. Treatment with the Ca2+ chelator, EGTA, or with inorganic Ca2+ blockers, including Co2+, Mn2+, and La3+, reduced the norepinephrine-stimulated response, suggesting that the alpha 1-adrenergic stimulation of phospholipase C activity is Ca2+ dependent. However, phospholipase C activity was not increased by elevating intracellular Ca2+ with either the Ca2+ ionophore A23187 or with depolarizing concentrations of K+. These results indicate that although Ca2+ is necessary for alpha 1-adrenergic stimulation of phospholipase C activity, an increase in [Ca2+]i alone is not sufficient to stimulate the activity of this enzyme, and that effects which A23187 and depolarizing concentrations of K+ have on pineal function probably do not involve stimulation of phospholipase C activity. PMID- 2906367 TI - Absolute bioavailability and dose proportionality of betaxolol in normal healthy subjects. AB - The absolute bioavailability and dose proportionality of betaxolol [(+/-)-1-(p-[2 cyclopropylmethoxy)ethyl]phenoxy]-3- (isopropylamino)-2-propanol hydrochloride], a cardioselective beta-adrenergic antagonist effective in the treatment of angina and hypertension, was studied in 12 healthy male subjects using a four-way crossover Latin Square design. Each subject received a 10-mg iv dose administered by constant-rate infusion over a period of 30 min and three oral doses (10, 20, and 40 mg). Blood and urine were collected over a 48-h period and analyzed for betaxolol using gas-liquid chromatography with electron capture detection. Maximum concentrations occurred 3-4 h after the dose. The maximum mean (+/- SD) blood concentrations normalized to the 10-mg oral dose were 21.6 +/- 3.7, 21.1 +/ 3.7, and 22.5 +/- 4.0 micrograms/L following the 10-, 20-, and 40-mg doses, respectively. A significant lag time of 10-80 min was observed after oral doses but was not related to dose size. The terminal slope (ts), absolute bioavailability (F), and renal clearance (CLr) were likewise not affected to an important degree by dose (ts: 0.043 +/- 0.006, 0.044 +/- 0.005, 0.046 +/- 0.006 h 1; F: 0.88 +/- 0.08, 0.82 +/- 0.06, 0.84 +/- 0.07; CLr: 0.68 +/- 0.22, 0.69 +/- 0.19, 0.65 +/- 0.22 mL/min kg). Unlike many beta-adrenergic antagonists, betaxolol has a long half-life (13-20 h) and high and consistent bioavailability (70-90%), and its disposition is independent of the size of the administered dose. PMID- 2906368 TI - An investigation of allogeneic pregnancy in multiparous mice subjected to in vivo depletion of CD8 (Ly2)-positive lymphocytes by monoclonal antibody treatment. AB - Adult thymectomized C57/Bl (H-2b) and DBA/1 (H-2q) female mice were subjected to treatment with rat anti-mouse CD8 and mouse anti-rat Ig (kappa) prior to entering their third pregnancy with CBA/Ca (H-2k) males. The treatment protocol drastically reduced the number of CD8 (Ly2)-carrying lymphocytes (T cytotoxic/suppressor phenotype) in the spleen and para-aortic lymph nodes, as assessed by immuno-staining. All mice were investigated on day 18 of their third gestation. The following data were collected from experimental and control groups: (1) resorption frequency, (2) weight of the placenta, fetuses, spleen and para-aortic lymph nodes, (3) immunohistochemical analysis of maternal lymphoid tissues, (4) level of anti-paternal IgG serum antibodies, (5) content of "background" IgM and IgG-secreting cells in spleen and para-aortic lymph nodes. Neither the resorption frequency nor placental/fetal weight was affected by anti CD8 treatment. However, the formation of anti-paternal antibodies was enhanced in anti-CD8 treated C57/Bl mice. PMID- 2906369 TI - Reduced levels of T suppressor/cytotoxic lymphocytes in semen from vasovasostomized men: relationship to sperm autoantibodies. AB - The regulation of lymphocyte populations in semen and their function remains unknown. Using monoclonal antibodies and immunohistochemical techniques we compared the levels of mononuclear cells in ejaculates obtained from 14 men with intact vas deferens and 13 men who had undergone both a vasectomy and a microsurgical vasovasostomy. The presence of antisperm antibodies was also assessed by the immunobead binding assay. Semen from both groups contained about 10(3) T and B lymphocytes and monocytes. In men with intact vasa, T suppressor/cytotoxic cells predominated. In contrast, in vasovasostomized men the levels of T suppressor/cytotoxic cells were significantly reduced (P less than 0.005) and T helper/inducer cells predominated in their semen. Concentrations of seminal T helper/inducer lymphocytes, B lymphocytes and monocytes were similar in both groups. Antisperm antibodies were detected on sperm, in seminal fluid and/or in serum of all the vasovasovasostomy patients but in none of the controls, T suppressor/cytotoxic cells may limit the immune response to sperm within the male reproductive tract. Chronic obstruction resulting in damage to the integrity of the excurrent ducts may induce alterations in T cell regulation leading to a decrease in T suppressor/cytotoxic cells and create conditions permissive for the formation of autoantibodies to sperm-specific antigens. PMID- 2906370 TI - Risk factor modification in hypertension--success and failure. AB - A group of 175 patients have attended for four years a microcomputer based, nurse practitioner managed clinic for the long term care of hypertension. Improvement in blood pressure (BP) control was seen initially and has been maintained. Drug treatment has been with a beta blocker followed if necessary by a diuretic and/or a vasodilator. Despite individual dietary and 'stop smoking' advice, there was no marked change in body weight while only males reduced smoking. A significant increase in non fasting serum cholesterol (6.4 +/- 1.3 to 6.6 +/- 1.3 mmol/l) and glucose (5.5 +/- to 6.1 +/- 2.5 mmol/l) was seen overall, but was restricted to those patients taking a thiazide diuretic (with or without other drugs). These findings indicate the need for a more systematic collection of information on effects of long term treatment and for the development of better strategies for improving lifestyle. PMID- 2906371 TI - Nifedipine substituted for minoxidil in the treatment of refractory hypertension. AB - Nifedipine slow release tablets were substituted for minoxidil in the treatment of 13 patients with hypertension refractory to conventional therapy. In 12 patients substitution was associated with continuing control of blood pressure (BP), although 11 required maximum dose of 120 mg daily and one 80 mg daily. BP control remained satisfactory in nine patients for at least one year after substitution and in all, loop diuretics previously required with minoxidil to control fluid retention, were discontinued. Three patients (23%) however had to be withdrawn because of side effects; one within days of starting therapy and two after three months: one patient died after sustaining myocardial infarction. There was no evidence of deterioration in renal function in those patients continuing on nifedipine. This drug in combination with other antihypertensive agents provides an alternative approach to the management of patients with refractory hypertension, avoiding the severe side effects of the potent vasodilators. PMID- 2906372 TI - Four DNA polymorphisms in the LDL receptor gene: their genetic relationship and use in the study of variation at the LDL receptor locus. AB - We have studied four different restriction fragment length polymorphisms (RFLPs) for the LDL receptor gene, detected using the restriction enzymes StuI, PvuII, ApaLI, and NcoI, in normal subjects and in patients with familial hypercholesterolaemia (FH) from London. Significant linkage disequilibrium was detected between all four RFLPs. Used together they give a polymorphism information content (PIC) of greater than 0.7 which makes them useful for studying the inheritance of the LDL receptor gene in more than 70% of families with FH. The NcoI and ApaLI RFLPs were found to be the most useful, giving a combined PIC value of 0.6. The allele frequencies of all four polymorphisms were compared in the normal and FH groups and the frequency of the rarer N2 allele of the NcoI RFLP was found to be significantly higher in the FH group. This suggests that a mutation has occurred on the rare NcoI N2 allele and that it may be making a significant contribution to the defects causing FH in this patient group. We have also used these RFLPs to look for evidence that variation at the LDL receptor gene locus contributes to the determination of cholesterol levels in the normal population. People with different RFLP genotypes do not have significantly different levels of serum total or LDL cholesterol. At present we have no evidence that variation at this locus may be determining cholesterol levels in the non-FH population. PMID- 2906373 TI - Mucosal neuromata syndrome (MEN type IIb (III)). PMID- 2906375 TI - [An operative case of multiple endocrine neoplasia type 1 (MEN type 1) with insulinoma]. PMID- 2906374 TI - Mechanism of inactivation of single sodium channels after modification by chloramine-T, sea anemone toxin and scorpion toxin. AB - Single sodium-channel currents were measured in neuroblastoma cells after inhibition of inactivation by chloramine-T (CHL-T), sea anemone toxin II (ATX-II) and scorpion toxin (SCT). The decaying phase of the averaged single-channel currents recorded with 90-msec pulses in cell-attached patches was clearly slower than that of the ummodified channels, suggesting inhibition of macroscopic inactivation. Each substance caused repetitive openings and a moderate increase in the channel open time. At Vm = RP + 20 mV and T = 12 degrees C, the mean channel open times were 1.4, 1.6 and 1.8 msec for CHL-T, ATX-II and SCT, respectively, as opposed to 1.07 msec for native channels. Open-time histograms could be best fitted by the sum of two exponentials. The time constants of the fits were similar for histograms constructed from single openings and from openings during bursts. This suggests that the population of channels is homogeneous and that in bursts the same open conformations of channels occur as in single openings. Mean burst durations for bursts consisting of more than one opening at Vm = RP + 20 mV were 4.9, 5.8 and 6.1 msec for CHL-T, ATX-II and SCT, respectively. Burst open-time histograms constructed from two or three openings were fitted by the gamma function. The different time constants of the fits obtained for ATX-II and SCT suggested multiple open conformations of channels for openings of bursts. However, significantly different open-time histograms constructed from the first, second and third openings of bursts could not be obtained systematically. A positive correlation was found for the dwell time of the first and the second, as well as for the second and the third opening of bursts with each substance, but a negative one for the dwell time of an opening and the neighboring closing of bursts with ATX-II. The results suggest a model with multiple open and inactivated states. In this model the inactivated states are weakly absorbing. PMID- 2906376 TI - [A method of central electroanalgesia for correcting the functional status of pilots during intensive flights]. AB - Optimal levels of the health status of pilots performing an intensive flight program can be maintained by rational work and rest schedules and correction methods. The effectiveness of central electroanalgesia as a correction method was determined. The course of treatment which consisted of 4-5 sessions, each 40-50 min long, produced a beneficial effect on the health status and work capacity of pilots as measured by direct and indirect methods. PMID- 2906377 TI - [Condition of the human skin during a stay in a hermetically closed compartment]. AB - The skin of healthy men kept in an enclosed environment was examined. It was found that exposure resulted in increases of the secretions of the sebaceous glands and sebum cutaneum, number and size of comedones, lipolytic activity of microorganisms, concentration of comedonogenic acids and skin irritating acids. It also caused a greater risk of papular and pustular rashes. Changes in lipid metabolism were consistent with the skin clinical state as well as with the subjective sensations of dirty skin, desquamation and itching. The severity of the above changes was correlated with the pretest physiological and hygienic status of the subjects. PMID- 2906378 TI - [Habitability and life support systems]. AB - This paper discusses various aspects of space vehicle habitability and life support systems. It describes variations in the chemical and microbial composition of an enclosed atmosphere during prolonged real and simulated flights. The paper gives a detailed description of life support systems and environmental investigations onboard the Mir station. It also outlines the development of space vehicle habitability and life support systems as related to future flights. PMID- 2906379 TI - [Biological life support systems for man]. AB - This paper discusses theoretical foundations of biological life support systems (BLSS), major stages of their development and performance parameters of BLSS models developed by the Institute of Biomedical Problems during the past 25 years. Comparison of the size and structure of these models with the structure of natural ecosystems allows the conclusion that BLSS can be operational in an environment that does not differ drastically from natural biocenoses in terms of living matter and basic ingredients, i.e. oxygen, carbon dioxide, water. PMID- 2906380 TI - [Pharmacologic correction of the effect of cold on man]. AB - The effect of pharmacological stimulants and prescriptions on the thermal status of man and their possible use to extend the exposure to the cold environment were investigated. The effectiveness of the following drugs and prescriptions was assessed: sydnocarb, phenamine, indopan; glutamic acid + lagochilus + ephedrine; sydnocarb + glutamic acid (sydnogluton); ephedrine + glutamic acid + strychnine. The test subjects were kept in air (in a thermal chamber) at -20 degrees C or in water at 0 to 2.5 degrees C (resting or swimming). The most effective treatment was provided by sydnocarb (effective doses were 10 mg X 2 or 30 mg X 5 in air or water, respectively) and sydnogluton (sydnocarb 30 mg + glutamic acid 0.25 g X 5 in cold water). When compared to placebo, sydnocarb (or sydnogluton) assured better thermal parameters of the body in cold water and longer (by 2-6 hrs) exposure which increased to 20 hrs. PMID- 2906381 TI - Determination of fentanyl in whole blood at subnanogram concentrations by dual capillary column gas chromatography with nitrogen sensitive detectors and gas chromatography/mass spectrometry. AB - Two methods for the determination of fentanyl at subnanogram concentrations in whole blood have been developed and evaluated. The initial screening was by gas chromatography with nitrogen sensitive detection (GC/NPD) in a splitless injection onto two fused-silica, 0.32-mm i.d. capillary columns (5% and 50% phenyl methyl silicone). Confirmation was by gas chromatography/mass spectrometry (GC/MS) using selected ion monitoring of a splitless injection onto a 0.1-mm i.d., 0.34-microns 5% phenyl methyl silicone capillary column. The methods were studied at fentanyl concentrations over the range 0.05 to 5.0 ng/mL using 2 mL of blood. The detection limits were set at 0.10 ng/mL for GC/NPD and 0.05 ng/mL for GC/MS. The overall recovery of fentanyl was found to be greater than 75% over the range of 0.25 to 2.5 ng/mL. The within-run precision determined at fentanyl concentrations of 0.25 and 1.0 ng/mL showed coefficients of variation ranging from 8.7 to 14.8%. The between-run precision determined at concentrations of 0.4 and 0.8 ng/mL showed coefficients of variation ranging from 3.3 to 11.6%. The blood calibration curves in the range of 0.25 to 2.5 ng/mL monitored over a 3 month period showed a mean correlation coefficient of 0.99 for both the GC/NPD and GC/MS methods. PMID- 2906382 TI - A novel procedure for the analysis of drugs in whole blood by homogeneous enzyme immunoassay (EMIT). AB - This paper describes a procedure for the analysis of whole blood by six commonly used EMIT d.a.u. assays: barbiturates, benzodiazepines, cocaine metabolite, opiates, amphetamines, and the cannabinoid 20 assays using the Syva Autocarousel and the COBAS MIRA. The sensitivity of the method rivals that of other immunoassay methods, such as RIA, for the detection of drugs in blood. The procedure has been successfully applied to the analysis of several hundred postmortem forensic blood specimens. PMID- 2906383 TI - [Indications for the use of Meuli's total wrist endoprosthesis]. PMID- 2906384 TI - [Reoperation in complications of surgical treatment of femur neck fractures]. PMID- 2906385 TI - [Instability of the wist joint (functional anatomy, forms of instability, diagnosis)]. PMID- 2906386 TI - [Surgical treatment of the posterior edge of the acetabulum using a molded titanium plate]. PMID- 2906387 TI - [Surgical treatment of inveterate ruptures of the rotator cuff by creating a tendon graft bridging of the defect]. PMID- 2906388 TI - [Arthroscopic surgery of the knee joint]. PMID- 2906389 TI - [Possibilities of after-treatment following surgery to mobilize the elbow joint]. PMID- 2906390 TI - [Importance of teaching catastrophic medicine]. PMID- 2906391 TI - [Development of the management of hand injuries in Veszprem County]. PMID- 2906392 TI - [The role of hospital surgical departments in the management of injuries]. PMID- 2906393 TI - Pharmacodynamic effects of a 2-piperazinotetralin (P-11)--combined alpha- and beta-adrenoceptor blocking drug with hypotensive action. AB - The piperazinotetralin derivative P-11 at hypotensive doses of 0.25 to 1.00 mg/kg i.v. reduced the pressor effects of exogenous noradrenaline (10 micrograms/kg i.v.) in reserpine-pretreated rats, but was ineffective in nonreserpinized normotensive urethane-anesthetized rats. P-11 (0.25 to 1.00 mg/kg i.v.) decreased the positive chronotropic effects of isoprenaline (0.2 micrograms/kg i.v.), but potentiated the isoprenaline-induced hypotension in reserpine-pretreated rats. P 11 (10(-7) to 10(-5)M) did not modify the concentration-effect curves for isoprenaline in carbachol-contracted guinea-pig tracheal strips. The pD2 value of isoprenaline was 5.94 before and 6.35 after P-11. The combined alpha1 postsynaptic antagonist/beta1-blocking activity of this compound is discussed. PMID- 2906394 TI - Involvement of peripheral dopaminergic mechanisms in the action of a 2 piperazinotetralin (P-11) with hypotensive activity. AB - The piperazinotetralin derivative P-11 applied in increasing concentrations (10( 12) to 10(-4)M) inhibited field electrical stimulation-induced contractions of isolated rabbit ear artery and this effect was not reversed by S-sulpiride (10( 6)M). This was probably due to the postsynaptic alpha receptor-blocking action of P-11. The compound also did not modify PGF2 alpha-induced contractions of isolated rabbit renal artery, suggesting the lack of action of P-11 on postsynaptic DA1 receptors. The lack of activity of P-11 on DA1 and DA2 peripheral receptors was associated with the chemical structure of the compound. PMID- 2906395 TI - Fatty acids as biological markers for bacterial symbionts in sponges. AB - Analyses of fatty acids with carbon numbers between C12 and C22 are reported for five Great Barrier Reef sponges. These analyses indicate that phototrophic cyanobacterial symbionts (blue-green algae) present in three of the sponges are chemically distinct, whereas the other two sponges do not contain cyanobacterial symbionts. All the sponges contain other, nonphototrophic bacteria. The fatty acid analyses indicate that the non-phototrophic bacterial populations present in the different sponges are distinct in both their chemical compositions and their abundances. Nonphototrophic bacteria are estimated to account for between 60 and 350 micrograms/g (extractable fatty acids:tissue wet weight), whereas cyanobacteria account for between 10 and 910 micrograms/g. One sponge (Pseudaxinyssa sp.) contains a relatively large amount of the isoprenoid acid, 4, 8, 12-trimethyltridecanoic acid; this acid is presumed to be derived from phytol, a degradation product of chlorophyll. This sponge also contains relatively large amounts of the nonmethylene interrupted fatty acid, octadeca-5,9-dienoic acid. Analyses of interior and cyanobacteria-rich surface tissues of this sponge indicate that these two acids are probably not associated with the symbiotic cyanobacteria. PMID- 2906396 TI - Haplotype analysis of a type I collagen gene and its association with alcoholic cirrhosis in man. PMID- 2906397 TI - [Nonsurgical treatment of hemorrhage caused by esophageal varices]. PMID- 2906398 TI - [Refractory duodenal ulcer: an emerging therapeutic problem]. PMID- 2906400 TI - Neuromodulation of hematopoiesis: a hypothesis. AB - The possibility that Hematopoiesis is under CNS control has been discussed in the literature; but never been conclusively proved at the molecular level. Evidence in the form of antigenic similarity between murine brain and the Stem Cell, and the decline in the number of Stem Cells following the lesioning of the Locus Coeruleus Nucleus exists. The recent establishment of the CNS control of the Immune System which had been previously proposed on similar evidence is discussed. It is suggested that the advances in the study of Colony Stimulating Factors (CSFs) provide an opportunity to test the role of Neurotransmitters on the proliferation/differentiation of Stem Cells. A series of experiments using CSF-dependent and CSF-independent cell lines and the biochemical basis of CSF activity to detect neurological influences are proposed. A model of a CNS regulatory mechanism is proposed, and used to explain many unexplained features of the in vivo activity of the CSFs. PMID- 2906399 TI - [In vitro effects of morphine and opioid peptides on granulocyte migration]. PMID- 2906401 TI - Structure of the ARO3 gene of Saccharomyces cerevisiae. AB - In Saccharomyces cerevisiae, the genes ARO3 and ARO4 encode isoenzymes of 3-deoxy D-arabino-heptulosonate-7-phosphate (DAHP) synthase. Both genes are derepressed seven-fold under the general control of amino acid biosynthesis. A previously isolated 1.7 kb fragment containing the ARO3 gene and the 5'- and 3'-flanking regions was sequenced. The endpoints of the ARO3 transcript coding for a 370 amino acid protein were mapped by primer extension experiments and S1 nuclease digestion. Promoter elements involved in transcription initiation and responsible for the strong general control derepression response are discussed. PMID- 2906402 TI - Specificity of action on mosquito larvae of Bacillus thuringiensis israelensis toxins encoded by two different genes. AB - A 135 kDa protein gene and two open reading frames (ORF1 and ORF2) have been cloned from a large plasmid of Bacillus thuringiensis israelensis (Bourgouin et al. 1986). The Escherichia coli recombinant clones containing these genes were highly toxic to larvae of Aedes aegypti, Anopheles stephensi and Culex pipiens. From subcloning experiments it was deduced that the 135 kDa polypeptide alone was responsible for the toxic activity on both A. aegypti and An. stephensi larvae. In contrast, the presence of two polypeptides, the 135 kDa protein and the ORF1 product was required for toxicity to C. pipiens larvae. The minimal toxic fragment of the 135 kDa polypeptide has been delineated. The results indicate that a polypeptide of about 65 kDa, corresponding to an amino-terminal part of the 135 kDa protein is sufficient for toxicity. Sequence comparisons indicate that the ORF1 product may correspond to an N-terminal part of a rearranged 130 kDa protein. PMID- 2906404 TI - [A technique for fabricating wrought wire clasps with metal rest by the room temperature casting method. Part 1: Evaluation of mechanical properties]. PMID- 2906403 TI - Molecular cloning and characterization of a negative-acting nitrogen regulatory gene of Neurospora crassa. AB - Expression of the structural genes of the nitrogen control circuit of Neurospora crassa is regulated by the positive-acting nit-2 control gene and by the negative acting nmr control gene. Nitrate reductase is expressed in a constitutive fashion in nmr mutant strains, which appear to be largely insensitive to nitrogen catabolite repression. Thus, nmr mutants are sensitive to chlorate in the presence of ammonia or glutamine, whereas the wild type is chlorate resistant under these conditions. A cosmid library was screened for the presence of the nmr+ gene by the sib selection procedure, and a single cosmid was isolated which transforms the nmr mutant to chlorate resistance at a high frequency. A restriction fragment length polymorphism analysis revealed that the cloned DNA segment maps to the precise genomic location of nmr. Northern blot analyses revealed that the nmr gene is itself not regulated but is expressed constitutively to give a single transcript of approximately 1.8 kb. PMID- 2906405 TI - [Dental soldering. Effects of the size of the invested block on adaptability]. PMID- 2906406 TI - [Dental soldering. Fitness accuracy of the soldering method with electrical taking]. PMID- 2906407 TI - [Dental soldering (Part 7). Effects of the space of the soldering gap on adaptability]. PMID- 2906408 TI - [Basic study on laser welding of Ag-Pd-Cu-Au alloy. Part 2. Mechanical properties and heat treatment]. PMID- 2906409 TI - The activation of phosphatidylinositol turnover is not directly involved in the modulation of neurotransmitter release mediated by presynaptic muscarinic receptors. AB - In the rat cerebral cortex, the comparative effects of various muscarinic agonists on the release of [3H]dopamine ([3H]DA), [3H]acetylcholine ([3H]ACh), and [3H]5-hydroxytryptamine ([3H]5-HT) from superfused nerve endings and on phosphatidylinositol (PI) turnover were studied. Acetylcholine (ACh) was found to be the most potent among the agonists tested on all three release systems examined, and also on the activation of PI turnover. Oxotremorine and bethanechol were very weak agonists when tested as stimulators of PI turnover. However, oxotremorine was very effective as a release modulator, while bethanechol was completely ineffective. Our data suggest that the activation of PI turnover is not directly involved in the modulation of neurotransmitter release mediated by presynaptic muscarinic receptors. PMID- 2906410 TI - Differentiating the effects of three benzodiazepines on non-REM sleep EEG spectra. A neural-network pattern classification analysis. AB - Neural-network pattern classifiers were used to study the effects of long half life flurazepam (30 mg) and quazepam (15 mg), and short half-life triazolam (0.5 mg) on non-REM sleep. We measured the magnitude of effect, time course, and EEG spectral signature of the three benzodiazepines as a function of third-of-night. Of the three benzodiazepines studied, flurazepam had the largest effect and quazepam had the most stable time course. The effects of triazolam were similar to those of quazepam. These EEG differences may prove to be more clinically useful markers than the usual measurement of plasma levels, and may be used to guide the therapy of sleep disorders. PMID- 2906411 TI - [Which therapy in the acute stage of myocardial infarct is in position to prolong survival?]. PMID- 2906412 TI - [Bopindolol in the treatment of mild and moderate arterial hypertension]. PMID- 2906413 TI - Use of 3'HVR genomic probe for presymptomatic diagnosis of adult polycystic kidney disease in northern Italy: comparison of DNA analysis and renal ultrasonographic data. AB - A highly polymorphic DNA probe (3'HVR) with genetic linkage to the locus of autosomal dominant polycystic kidney disease was used for screening. Families with subjects at risk were from the Po river delta region (Northern Italy), where the disease accounts for 24% of the demands for dialysis. 3'HVR alleles were investigated in white blood cell DNA from 142 members of 18 families. The genomic marker was found informative in 88% of cases. Two recombinations between the marker and the disease locus were observed in 79 meioses. In 42 of the subjects at risk the results of DNA analysis and renal ultrasonography were compared. In 36 subjects the tests confirmed each other (18 were positive). In the other six subjects (all under 20 years of age and four under 10) only DNA analysis could diagnose the inheritance of cystic disease in the absence of demonstrable cysts. The findings indicate that in the population of the Po river delta the presymptomatic detection of adult polycystic kidney disease by 3'HVR linkage analysis is feasible in 88% of cases with approximately 95% reliability. PMID- 2906414 TI - An N-methyl-D-aspartate receptor mediated excitatory postsynaptic potential evoked in subthalamic neurons in an in vitro slice preparation of the rat. AB - Subthalamic (STH) neurons with slow EPSPs mediated by an N-methyl-D-aspartate (NMDA) receptor were studied in rat brain slice preparation. When STH neurons were intracellularly recorded with KCl-filled electrodes, stimulation of the internal capsule (IC) evoked a short duration depolarization followed by a slow excitatory postsynaptic potential (EPSP) lasting 100-200 ms. The amplitude of the slow EPSP was increased when the neuron was hyperpolarized by a low intensity current injection but was blocked when it was hyperpolarized with strong current. The slow EPSP was reversibly suppressed by application of 30-50 microM DL-2-amino 5-phosphonovareric acid (APV). STH neurons also were recorded, with potassium methylsulfate filled electrodes, in the slice preparation obtained from rats that received chronic knife cuts of the IC at the level of the entopeduncular nucleus. Stimulation of the IC immediately rostral to the STH evoked a fast EPSP followed by a slow EPSP, and IPSPs were largely eliminated in this preparation. The slow EPSP was augmented in MG-free medium and suppressed by 50 microM APV. These results suggest that NMDA receptor mediating slow EPSPs may regulate activities of STH neurons. PMID- 2906415 TI - Microinjections of glutamate or morphine at coincident midbrain sites have different effects on nociceptive dorsal horn neurons in the rat. AB - Responses of single lumbar spinal neurons to noxious skin heating (50 degrees C, 10 s) were electrophysiologically recorded in barbiturate-anesthetized rats. Responses of all neurons were suppressed by electrical stimulation in the midbrain periaqueductal gray (PAG) or lateral reticular formation (LRF). Microinjection of glutamate (GLU, 0.1-0.3 microliter, 0.5 M) into the PAG rapidly (within 15 s) suppressed (to 13-55% of control) the responses of 6/16 neurons with recovery within 8 min. The remainder were affected less at even higher doses (0.5-1 microliter). Responses of 4/10 neurons were suppressed following GLU microinjected into the LRF. We also tested effects of microinjection of morphine (MOR, 5 micrograms/0.5 microliter) into GLU-sensitive and insensitive PAG sites. Responses of 4 neurons were unaffected, 4 were enhanced (to 130-155%), and 2 suppressed (to 43 and 57%) following MOR in PAG, with enhancement or suppression beginning within 12-20 min and lasting 40 to over 70 min. The differing effects of GLU and MOR may reflect different mechanisms for the descending modulation of spinal nociceptive transmission. PMID- 2906416 TI - Ring-substituted amphetamine interactions with neurotransmitter receptor binding sites in human cortex. AB - The binding affinities of 3 ring-substituted amphetamine compounds were determined at 9 neurotransmitter binding sites in human cortex. (+/-)-3,4 Methylenedioxyamphetamine (MDA), (+/-)-3,4-methylenedioxyethamphetamine (MDE), and (+/-)-3,4-methylenedioxymethamphetamine (MDMA or 'Ecstasy') all display highest affinity (approximately 1 microM) for the recently identified 'DOB binding site' labeled by [77Br]R(-)4-bromo-2,5-dimethoxyphenylisopropylamine [( 77Br]R(-)DOB). MDA displays moderate affinity (4-5 microM) for the 5 hydroxytryptamine1A (5-HT1A), 5-HT1D, and alpha 2-adrenergic sites in human cortex. MDE and MDMA display lower affinity or are inactive at all other sites tested in the present study. These observations are discussed in relation to the novel psychoactive effects of the ring-substituted amphetamines. PMID- 2906417 TI - Reproductive hormones control striatal tyrosine hydroxylase activity in the male rat. AB - The effects of castration, hypophysectomy and testosterone treatment on striatal tyrosine hydroxylase (TOH) activity were examined in male rats. Enzyme activity was measured by means of high-performance liquid chromatography (HPLC) determination of L-3,4-dihydroxphenylalanine (DOPA) formed. Serum levels of both testosterone and luteinizing hormone (LH) were measured by radioimmunoassay (RIA). Castration, but not hypophysectomy, reduced TOH activity in the striatum. The administration of testosterone propionate (TP) to castrated animals in a dose of 10 micrograms/100 g b.wt. during the two days previous to sacrifice, completely prevented the castration-induced reduction of striatal TOH activity. In orchidectomized rats treated with different doses of testosterone propionate (TP) up to 20 micrograms/100 g b.wt., the levels of striatal TOH activity were apparently related to either the dose-related increase of serum testosterone or the decrease of serum LH. Higher doses of the androgen failed to further modify striatal TOH activity, in spite of the dose-related elevation of serum testosterone concentration. These results suggest that circulating levels of gonadal and/or pituitary hormones partially control dopaminergic synthesis in striatal terminals, which in turn may account for some behavioral effects of reproductive hormones. PMID- 2906418 TI - Comparative topography of dopamine- and tyrosine hydroxylase-immunoreactive neurons in the rat arcuate nucleus. AB - The distribution of dopamine (DA)-immunoreactive (IR) cells is described in the rat arcuate nucleus of the hypothalamus and its adjacent areas and compared with that of tyrosine hydroxylase (TH)-IR cells. Small DA-IR cells were seen to be aggregated mainly in the dorsomedial part of the nucleus, but were hardly detectable in its ventrolateral portion and neighbouring periarcuate region which showed many larger TH-IR cells. This study reveals, for the first time, the differences in the respective topography of those neurons which actually contain detectable DA and those which contain TH, the initial synthesizing enzyme of catecholamine. PMID- 2906419 TI - Sulfasalazine inhibits folate absorption. PMID- 2906420 TI - Dopamine, GABA, cholecystokinin and opioids in neuroleptic-induced tardive dyskinesia. AB - The long-term administration of neuroleptics causes tardive dyskinesia, which closely resembles levodopa-induced dyskinesias, and is brought about through complex mechanisms which are ill-defined. It is generally believed that the pathogenesis of tardive dyskinesia relates closely to the chronic blockade of dopamine receptor sites and that its pathophysiology results from a hypersensitivity of dopamine receptor sites. In the therapeutic management of neuroleptic-induced tardive dyskinesia, in addition to reserpine and lithium, diazepam, baclofen, or gamma-vinyl-gamma-aminobutyric acid have also been advocated. However, the reported beneficial effects of diazepam and GABA-mimetic agents in ameliorating the symptoms of tardive dyskinesia may occur through a mechanism which does not necessarily link transmission involving both dopamine and GABA. The presence of high concentrations of both cholecystokinin and opioids in the striatum also suggests that these peptides not only may influence dopaminergic transmission, but that they may also be relevant to the psychopathology of schizophrenia and to the therapeutic effects of neuroleptics. Indeed, the acute and chronic administration of neuroleptics alters the levels of cholecystokinin and opioids and their receptors in several brain regions including the striatum. However, neuroleptics also alter the biochemical integrity of neurotensin, neuropeptide Y, substance P and somatostatin, which may also play a role in the overall expression of the neuroleptic-induced extrapyramidal reactions. PMID- 2906421 TI - Tourette syndrome and medical treatment in Canada. AB - Self-report data were gathered from a national sample of over two hundred Canadian Tourette Syndrome (TS) patients. Included was previous use of stimulant medication and prior extended use of antihistamines for allergies or sinus condition. Patients were also asked information on Tourette Syndrome-precipitated hospitalization or boarding school placement, the type of physician treating them and on a five-point scale their level of satisfaction with their medical care. Results indicate that over 20% of TS patients have used stimulant medications and 30% have used antihistamine for extended periods. Many patients have spent time in psychiatric settings and most are under the care of psychiatrist or neurologist. Approximately 40% of TS patients reported being satisfied to very satisfied with the medical care they were receiving, and 20% having mixed feelings. Few patients receiving medical care were dissatisfied with their treatment. PMID- 2906422 TI - Intermittent medication cessation in the treatment of Tourette syndrome. AB - Long-term use of neuroleptic medications has been associated with many undesirable effects. Intermittent medication cessation may reduce the risk of exposure to these side effects. Six school age male Tourette Syndrome (TS) patients who were on medication for TS (haloperidol) were monitored closely over a six-month period. Four patients withdrew from haloperidol for the middle two month period then returned to medication use. Other subjects remained on medication throughout the study. Results indicated that withdrawal from haloperidol is likely to result in an increase in TS symptoms, particularly simple motor tics, which is quite dramatic but rarely lasts more than 4 weeks. Physical symptoms of withdrawal from haloperidol include irritability, nervousness, moodiness, oppositional behaviours, stomach pains, indigestion, skin irritations, diaphoresis, visual acuity problems, oculogyria, and symptom instability. Results of psychometric tests also indicated, however, that subjects were less depressed, experienced fewer obsessive-compulsive symptoms, and were less hyperactive and socially withdrawn when they were medication free as compared to on haloperidol. PMID- 2906423 TI - A clinical pharmacological approach to treating Tourette syndrome in children and adolescents. AB - Tourette Syndrome (TS) is a neuropsychiatric movement disorder characterized by the presence of multiple motor and phonic tics. Monoamine neurotransmitter dysfunction has been implicated in the expression of the condition. Standard as well as novel pharmacologic treatments for TS as a sole entity or as a condition co-morbid with attention deficit-hyperactivity disorder (ADHD) and/or obsessive compulsive disorder (OCD) target these presumed neurotransmitter abnormalities. Choice of a specific medication is also predicated upon an individual patient's symptom profile, a cost-benefit analysis of desired effects versus side effects, and the impact on co-morbid conditions. Maximum involvement of the patient and parent or significant other is encouraged. It is emphasized that pharmacologic treatment is primarily symptomatic, usually not affecting the longer term outcome of specific syndromes per se. The integration of pharmacologic with psychoeducational interventions is encouraged. PMID- 2906424 TI - An evaluation of Tourette syndrome and medication use in Canada. AB - Self-report data were gathered from a national sample of over 200 Canadian Tourette Syndrome (TS) patients. Information regarding symptom severity both on and off medication was gathered along with an analysis of different medications in use, and patient ratings of effectiveness of those medications. Patients also rated their own mental health. Results indicated that approximately 60% of TS patients take some form of medication for relief from their symptoms. Of these, over 80% reported that symptoms are less severe when medicated. The most commonly prescribed medications in order of popularity are haloperidol, pimozide, clonidine and benztropine mesylate (Cogentin). Patient ratings of effectiveness of these medications places haloperidol first, pimozide second and clonidine third although all were found to be "somewhat" to "very" effective. Of those TS patients on medications, 50% rated their own mental health as good to excellent and 50% rated it as fair to poor. PMID- 2906425 TI - Inflammation of the hind limb as a model of unilateral, localized pain: influence on multiple opioid systems in the spinal cord of the rat. AB - Inoculation of the right hind paw with Mycobacterium butyricum rapidly led to swelling and inflammation. The afflicted limb showed an enhanced sensitivity to noxious pressure (hyperalgesia) and a reduced sensitivity to noxious heat 24 h following treatment. Both naloxone and MR 2266 (which has greater activity at kappa-opioid receptors) further increased the sensitivity to pressure (that is, potentiated the hyperalgesia) but did not affect the response to heat. They did not affect the response of the uninflamed paw. At 1 week, only MR 2266 was effective. At both 24 h and 1 week, the inflamed paw showed pronounced supersensitivity to the antinociceptive action of morphine against noxious pressure. At both 24 h and (to a greater extent) 1 week, a rise in levels of immunoreactive (ir)-dynorphin (DYN) was seen in the ipsilateral dorsal horn of the lumbar spinal cord. There was no alteration in the contralateral dorsal horn or in either ventral horn. Furthermore, levels of ir-met-enkephalin (ME) and ir leu-enkephalin (LE) were unaffected. There was no difference in the density of mu , delta- or kappa-binding sites in any part of the lumbar cord, at either 24 h or 1 week, between ipsilateral and contralateral tissue. By 3 and 5 weeks postinoculation, the symptoms had spread to the contralateral hind limb and ir DYN was elevated in the contralateral dorsal horn and the ipsilateral ventral horn. At 5 weeks, levels of ir-ME and ir-LE also were increased in the ipsilateral and contralateral dorsal horns, but not in the contralateral ventral horn. Furthermore, levels of ir-DYN were increased in the cervico-thoracic spinal cord, and rats displayed adrenal hypertrophy and a rise in plasma levels of ir beta-endorphin (beta-EP). These data indicate: (1) Peripheral inflammation localized to a single limb selectively modifies levels of ir-DYN in ipsilateral dorsal horn. The effect is specific to DYN as compared to ME and LE. The density of mu-, delta-, or kappa-receptors in the lumbar spinal cord is unmodified. (2) The altered response to opioid agonists and antagonists shown by rats with an inflamed limb may be selective to the injured tissue. (3) Alterations in opioid systems associated with unilateral hind limb inflammation may not be exclusively chronic in nature: they appear very rapidly (within 24 h) of the induction of pain. With time, the contralateral limb becomes affected and, eventually, the effects resemble those seen with generalized polyarthritis. PMID- 2906426 TI - Enhancement of dynorphin gene expression in spinal cord following experimental inflammation: stimulus specificity, behavioral parameters and opioid receptor binding. AB - The stimulus specificity for enhancement of dynorphin gene expression in rat spinal cord was studied by combined measurements of the peptide dynorphin A 1-8 and preprodynorphin mRNA levels during peripheral inflammation induced by several agents. The density of kappa receptors, the putative receptor for dynorphin peptides, was examined using receptor binding with autoradiographic visualization. Mu and delta receptor classes were also studied. All inflammatory agents tested (carrageenan, phorbol ester, yeast and Freund's adjuvant) rapidly induced edema and thermal hyperalgesia. All agents also induced a rapid (within 8 h) elevation in dynorphin mRNA and, in comparison, a delayed (within 2 days) elevation of dynorphin A 1-8 peptide; peak peptide levels were reached at 4 days. No alteration of kappa, mu or delta receptor binding was observed at 4 h or 4 days post inflammation. The rapid development of thermal hyperalgesia and elevation of dynorphin mRNA and peptide content indicates that the involvement of dynorphin-containing neurons in nociceptive processing does not require a chronic abnormality and a dynamic picture of opioid modulation of sensory processing emerges. These data also demonstrate that activation of dynorphin biosynthesis in spinal cord is a feature common to hyperalgesia and peripheral inflammation and is not restricted to any one type of inflammatory agent. The lack of alteration in receptors suggests that the physiological effects of an increased biosynthesis are not accompanied by a concurrent down-regulation of opiate receptors. PMID- 2906427 TI - Studies on essential amino acid residues and functional regions of H+-ATPase (F0F1) from Escherichia coli by gene manipulation. AB - We discussed application of in vitro mutagenesis on H+-ATPase (F0F1) of Escherichia coli. The oligonucleotide-directed site specific mutagenesis and construction of a set of truncated subunits were useful for identifying essential residues of beta subunit and a functional region of epsilon subunit, respectively, of this complicated membrane enzyme. PMID- 2906428 TI - A rapid and efficient purification of poly(A)-mRNA by oligo(dT)30-Latex. AB - Latex particles were covalently linked to the 5'-proximal region of oligo(dT)30. The resultant oligo(dT)30-Latex was tested for its hybridizability to poly(A) containing mRNA. Several advantages were noted as compared to the conventional oligo(dT)30-cellulose column chromatography; (1) a highly efficient (approximately 95%) hybridization occurs in a short reaction period (10min), (2) more than 95% of poly(A) mRNA can be recovered from oligo(dT)30-Latex by a simple heating followed by brief centrifugation, (3) multiple samples can be handled simultaneously and moreover, (4) the poly(A)-mRNA on the oligo(dT)30-Latex can be directly transcribed by AMV reverse transcriptase to form the cDNA. These properties of oligo(dT)30-Latex promise an excellent reagent for nucleic acid technology. PMID- 2906429 TI - Neuroleptic-like properties of cholecystokinin analogs: distinctive mechanisms underlying similar behavioral profiles depending on the route of administration. AB - Rats were trained to discriminate vehicle injections from intraperitoneal injections of 3 micrograms/kg caerulein, a cholecystokinin (CCK) neuropeptide analog. The reward that reinforced correct choices was an electrical brain stimulation self-administered by bar pressing. Dose-response quantitative generalization was obtained by using 1 and 2 micrograms/kg caerulein. Qualitative generalization to the vehicle occurred after injecting 10, 20 and 200 micrograms/kg unsulfated CCK-8, 10, 20 and 200 micrograms/kg CCK-4, 5 micrograms/kg CCK-8 and 1 microgram/kg caerulein, neurotensin or bombesin and 200 micrograms/kg apomorphine or 320 micrograms/kg amphetamine. Total generalization to the caerulein cue was obtained with 20 micrograms/kg sulfated CCK-8 or gastrin 2-17, 25 micrograms/kg somatostatin, 50 micrograms/kg haloperidol and 2 mg/kg chlorpromazine. The previous 5 mg/kg injection of an antiemetic drug such as chlorhydrate of trimethobenzamide did not eliminate the discriminative properties of a subsequent injection of caerulein. Our data thus tend to show that IP injection of caerulein produces effects similar to those of IP neuroleptics. PMID- 2906431 TI - Hippocampal kynurenines as etiological factors in seizure disorders. AB - Seizure disorders are believed to be frequently linked to an imbalance between excitatory and inhibitory processes in the hippocampal formation. Thus, epileptic phenomena can probably be caused by a net hyperexcitation of hippocampal "pacemaker" neurons, which in turn leads to more generalized excitation and is often accompanied by selective neuronal loss. Several transmitter systems have been implicated in the etiology of seizures. However, the close mimicry of some forms of epilepsy by the actions of neuroexcitatory amino acids (EAA) and the anticonvulsant activity of EAA antagonists acting at the N-methyl-D-aspartate (NMDA) receptor have focussed recent attention on EAA as trigger factors in epilepsy. The heterocyclic metabolite quinolinic acid (QUIN), a NMDA agonist present in the brain, has attracted particular interest in this regard because of its potent convulsant and neurodegenerative properties, which are especially pronounced in the hippocampus. QUIN's metabolic enzymes have been identified in the brain and localized by immunohistochemical techniques to glial cells. Notably, QUIN biosynthesis seems to take place in cellular entities which are distinct from those responsible for QUIN degradation, implying that QUIN can gain access to the extracellular space (where it can interact with neuronal NMDA receptors) and can subsequently enter different cells to meet its catabolic fate. An endogenous compound metabolically related to QUIN, kynurenic acid (KYNA) is a potent antagonist of the convulsant and neurodegenerative effects of QUIN. The pathogenesis of seizure disorders can therefore now be hypothesized to be a problem of KYNA-deficiency as well as (or in addition to) QUIN-hyperfunction. It thus seems prudent to carefully examine the relationship between the function of QUIN and KYNA in the brain in view of possible implications for the precipitation of seizure phenomena. PMID- 2906430 TI - Sauvagine: effects on gastric acid secretion in rats. AB - Intracerebroventricular (ICV) and subcutaneous (SC) injections of sauvagine powerfully inhibited gastric acid secretion stimulated by gastric distension and by 2-deoxy-D-glucose, but not by histamine in pylorus-ligated rats. Naloxone failed to antagonize the antisecretory effects of SC and ICV sauvagine. Intravenous infusion of sauvagine completely suppressed bethanechol-stimulated gastric secretion, significantly decreased pentagastrin-stimulated gastric secretion and did not modify histamine-stimulated gastric secretion in gastric perfused rats. The inhibitory effect of sauvagine on gastric secretory response is not mediated through opioid or histamine receptors. It appears to be dependent on a vagal mechanism as well as other mechanisms that await further elucidation. PMID- 2906432 TI - Enkephalins and the action of psychotropic drugs. AB - This paper reviews data concerning the possible role of opioid neuropeptides in the central action of psychotropic drugs. The results summarized provide an evidence that the long term interruption of the central dopaminergic mechanisms by administration of neuroleptics causes specific alterations in the content, release and biosynthesis of several opioid peptides. Moreover, the dynamic changes of the enkephalin level in brain structures after one year of fluphenazine administration were described. The acute and chronic treatment with benzodiazepines induced pronounced changes in brain enkephalin concentrations. The first evidences are provided that chronic antidepressant treatment changes the level of enkephalins in discrete brain areas. PMID- 2906433 TI - Benzodiazepines increase tonic component of postdecapitation convulsions in mice. AB - The effects of benzodiazepines (BDZs) and GABA system on tonic and clonic component of postdecapitation convulsion (PDC) were studied in mice. Mice decapitated at the occipito-cervical junction, exerted biphasic convulsions, i.e., initially tonic and subsequently clonic convulsions. BDZs such as diazepam or clonazepam increased tonic and clonic components of PDC. These effects were not antagonized by Ro 15-1788, a benzodiazepine receptor antagonist. The increased tonic component was antagonized by the GABA receptor antagonists, bicuculline and picrotoxin, whereas the clonic component was augmented by them. Aminooxyacetic acid, which increases the endogenous GABA content by inhibiting the GABA-transaminase, increased the tonic component significantly; this increase was antagonized by both bicuculline and picrotoxin. Muscimol, a GABA agonist, however did not affect the tonic components but rather augmented the clonic component. Bicuculline and picrotoxin did not antagonize this effect of muscimol. These results indicate that endogenous GABA may play a crucial role in mediating the tonic component of PDC and the facilitation of this component by BDZs may also be due to the activation of GABA in the spinal cord. Furthermore, the mechanisms of the tonic component may be different from that of the clonic component. PMID- 2906434 TI - Effects of isofloxythepin enantiomers on prolactin secretion and postdecapitation convulsions in rats. AB - Racemic isofloxythepin and its enantiomers (0.05-1.0 mg/kg) administered subcutaneously increased serum prolactin levels in a dose-dependent manner in rats. The potencies of the drugs were equal for this variable. They (0.05-1.0 mg/kg, SC) also decreased dose-dependently the incidence and duration of postdecapitation convulsions, the convulsions being abolished at 1.0 mg/kg in all groups. Although (-)-enantiomer had slightly stronger effects than those of raceme and (+)-enantiomer, there were no great differences in their inhibitory effects on postdecapitation convulsions. The results indicate that isofloxythepin enantiomers in addition to raceme increase serum prolactin levels and inhibit postdecapitation convulsions and that they seem to have similar potency in blocking of dopamine receptors and alpha 1-adrenoceptors. PMID- 2906435 TI - CGS 10746B is able to attenuate the effects of amphetamine: further evidence for dopaminergic mediation. AB - Previous results indicate that agents which either decreases synthesis or block postsynaptic dopamine receptors will attenuate the discriminative stimulus produced by d-amphetamine. CGS 10746B has been reported to decrease dopamine release without changing its metabolism or occupying its receptors. In the present study, rats successfully trained to discriminate intraperitoneally administered (0.8 mg/kg) d-amphetamine in a two-lever, food-motivated operant task were observed to be unable to discriminate amphetamine when pretreated with 30 mg/kg CGS 10746B. This antagonism was shown to be dose-responsive and constitutes a third mechanism, i.e., dopamine release inhibition, that evidences the dopaminergic mediation of amphetamine in the discriminative paradigm. When both cathinone (0.8 mg/kg) and cocaine (10.0 mg/kg) were administered to the amphetamine-trained rats they each were recognized as amphetamine and are, thus, considered to generalize to the amphetamine discriminative stimulus. Coadministration of CGS 10746B and cathinone totally antagonized this generalization, whereas pretreatment with CGS 10746B prior to cocaine significantly reduced cocaine's effects. These results implicate dopamine mechanisms in the discriminative stimulus properties of the psychostimulants amphetamine, cathinone and cocaine. PMID- 2906436 TI - Does RO 15-4513 reverse the anxiolytic effects of ethanol by its intrinsic properties? AB - In order to better understand the antagonistic effects of the partial inverse agonist of benzodiazepine receptors, RO 15-4513, against the disinhibitory action of ethanol, we examined the effects of RO 15-4513 at a dose (2.0 mg/kg) that did not alter locomotor activity, given alone or in combination with ethanol, on the behavior of mice confronted with the light/dark choice procedure and the staircase test. At this dose, RO 15-4513 given alone was found to have slight anxiogenic properties and when given in combination with ethanol, to completely reverse the disinhibitory effects of ethanol. Since we previously observed postictal depression after higher doses of RO 15-4513 given alone and antagonistic effects of these same doses on the action of ethanol, it can be suggested that the antagonistic effects of RO 15-4513 against ethanol are due to its anxiogenic or depressive properties depending on doses. However, this hypothesis can only be regarded as being in early stages of development at the present time since these results do not parallel with those of several other studies and the question whether the antagonistic action of RO 15-4513 against ethanol is additive or interactive remains open. PMID- 2906437 TI - Vascular actions of atrial natriuretic peptide. PMID- 2906438 TI - Antibronchoconstrictor activity of the intracellular calcium antagonist HA 1004 in guinea pigs. AB - HA 1004 is a calcium antagonist vasodilator that inhibits contraction in vascular smooth muscle and lowers arterial blood pressure. The effects of HA 1004 on guinea pig airway smooth muscle contraction were compared to the effects of the calcium antagonists, verapamil and nifedipine and the bronchodilator, albuterol. In vitro, HA 1004, verapamil, nifedipine and albuterol inhibited Ca2+-induced contractions of the depolarized guinea pig trachea. HA 1004 and albuterol also relaxed the basal tracheal tone, whereas verapamil and nifedipine were inactive. The bronchorelaxant activity of HA 1004 was not blocked by propranolol. In vivo, intravenous administration of HA 1004, verapamil, nifedipine and albuterol effectively blocked bronchoconstriction induced by intravenous histamine and methacholine. HA 1004 also reversed a histamine-induced bronchospasm, as did albuterol, verapamil and nifedipine. Intratracheal administration of HA 1004 and albuterol inhibited histamine-induced bronchoconstriction without effecting blood pressure, whereas intratracheal administration of verapamil and nifedipine caused a significant reduction of blood pressure at their pulmonary active doses. These results show that HA 1004 has the ability to relax airway smooth muscle, inhibit contractile responses in the guinea pig airways, and there is separation of its cardiovascular and pulmonary effects when HA 1004 is administered directly to the lungs. The results are discussed in terms of the regulatory enzymes and sources of calcium that are involved in airway smooth muscle contraction. PMID- 2906439 TI - Psychostimulants, analeptics, nootropics: an attempt to differentiate and assess drugs designed for the treatment of impaired brain functions. AB - The common characteristic properties of psychostimulants, analeptics, and nootropics are excitatory and disinhibitory effects on the central nervous system. The differences lie in the type of excitatory effect. Psychostimulants produce a general, yet nonphysiologic, activation with subsequent sedation. They generally act in a destabilising manner, disturbing the homoeostatic functions of centrally regulated reactions. Nootropics produce a physiological activation of disturbed or reduced adaptation functions. They have a stabilising effect, increasing the homoeostatic functions of the centrally regulated reactions that have become susceptible to disturbances. Analeptics differ from psychostimulants and nootropics. The effects of neuronal excitation or disinhibition are mainly restricted to the respiratory and circulatory systems. In high dosages they produce convulsions and corresponding motor reactions. No conclusive evidence for a general efficacy in the treatment of organic mental disorders has been furnished for any of the three drug classes. Yet there is sufficient proof that nootropics, unlike psychostimulants and analeptics, can produce therapeutic results in at least some patients, even if it is not yet clear under what conditions they can be meaningfully applied. There is a fundamental difference between the three groups with regard to the potential for abuse. While tolerance and extreme physiological dependence can occur rapidly under treatment with psychostimulants, such risks are not a typical feature of nootropics or analeptics. PMID- 2906440 TI - Systemic hormonal and physiological abnormalities in anxiety disorders. AB - Among the studies of systemic hormonal and physiological abnormalities associated with anxiety disorders, the most consistent and extensive findings suggest (a) peripheral adrenergic hyperactivity (including increases in norepinephrine but not epinephrine) and functional dysregulation, (b) increased incidence of mitral valve prolapse in panic patients, and (c) normal suppressibility of the hypothalamic-pituitary-adrenal cortical endocrine system with dexamethasone in panic patients. Other less-certain findings include (a) increased circulating concentrations of plasma ACTH and/or cortisol, and prolactin, in panic patients, (b) increased platelet monoamine oxidase activity in generalized anxiety and/or panic patients, (c) decreased gonadal axis activity in some anxious individuals, (d) decreased nighttime melatonin plasma concentrations in panic patients, and (e) peripheral alpha 2 and beta-adrenoreceptor down-regulation, with normal serotonin binding parameters. These findings, taken together, provide tentative support for dysfunction in adrenergic and GABAergic central nervous system mechanisms in people with anxiety disorders. Abnormal anxiety and normal stress both show evidence of adrenergic hyperactivity; however, there appear to be differences in hormonal profiles, especially the apparent lack of increase of epinephrine during panic attacks, as well as differences in the reactivity of the system, and in the "trigger" mechanisms which determine when the response occurs. PMID- 2906441 TI - Plasma prolactin response to gonadotropin-releasing hormone during benzodiazepine treatment. AB - Previously we observed that prolactin (PRL) is secreted in response to gonadotropin-releasing hormone (GnRH) in normal women during the periovulatory phase of the menstrual cycle. Because sedative drugs affect the neurotransmitters involved in the regulation of PRL secretion, we investigated PRL responsiveness to GnRH in pre- and postmenopausal female subjects during prolonged treatment with benzodiazepines (six-60 months). In both pre-and postmenopausal patients who were not on benzodiazepine treatment, GnRH infusion (0.2 micrograms/min for 3 hr) was ineffective in eliciting a PRL response. In six premenopausal women treated with benzodiazepines, basal PRL concentrations were not influenced by the drug in four subjects (range 4.0-15.7 ng/ml) and were slightly elevated in two subjects (23 and 30 ng/ml). In six treated postmenopausal women, basal PRL concentrations were in the normal range (7.5-11.0 ng/ml). GnRH infusion induced a progressive increase in PRL concentrations which reached a peak at 120 min in the premenopausal subjects (mean % SEM increase: 64 +/- 30.5%) and at 60-90 min in the postmenopausal subjects (mean % increase: 110.6 +/- 34.7%). A saline infusion, performed on a separate day during benzodiazepine treatment as a control, did not influence PRL. PMID- 2906442 TI - Apomorphine anorexia: the role of dopamine receptors in the ventral forebrain. AB - The inhibition of feeding following the administration of apomorphine, systemically or directly into the nucleus accumbens/ventral striatum, was studied using a microstructural analysis paradigm. On systemic administration, apomorphine reduced food consumption, eating rate and eating time; the effects were blocked by sulpiride but not by SCH-23390. Two doses of apomorphine were administered centrally. Both doses reduced total food intake and eating rate; only the higher dose also reduced eating time; all of these effects were blocked by sulpiride pretreatment. Only the lower dose reduced locomotor activity and rearing in the open field. The results suggest that apomorphine reduces eating rate by an action on dopamine (DA) axon terminal autoreceptors. We have previously demonstrated that apomorphine reduces eating time by an action on DA cell body autoreceptors. Therefore, the two populations of DA autoreceptors appear to be differentially involved in behaviour. PMID- 2906443 TI - The pharmacological characterisation of pilocarpine-induced purposeless chewing behaviour in the rat. AB - Purposeless chewing in rats was induced by the acute administration of the cholinergic agonist pilocarpine or by physostigmine. Pilocarpine-induced chewing was antagonised by the centrally acting anticholinergic drugs scopolamine, benzhexol and secoverine, but not by the peripherally acting anticholinergic drug methylscopolamine. Both benzhexol and secoverine caused dose-dependent inhibition of pilocarpine-induced chewing. The D-2 antagonist sulpiride and the D-1 antagonist SCH 23390 did not inhibit pilocarpine-induced chewing. The non selective neuroleptics pimozide, trifluoperazine and thioridazine also were inactive. In contrast, clozapine caused a dose-related inhibition of pilocarpine induced chewing. The alpha-1 antagonist prazosin, the alpha-2 antagonist idazoxan, the beta-antagonists propranolol and metoprolol and the H-1 antagonist mepyramine did not reduce pilocarpine-induced chewing. Purposeless chewing behaviour induced by pilocarpine was reduced in a dose-related manner by the administration of the 5-HT antagonists methiothepin and mianserin, but not by spiperone or ketanserin. These data confirm that pilocarpine-induced chewing behaviour in the rat is a model of central cholinergic activity, but suggest that a serotonergic component may be involved in the mediation of this behaviour. PMID- 2906444 TI - Time course of ethanol's effects on locomotor activity, exploration and anxiety in mice. AB - The time course of the effects of two doses of ethanol on exploration, locomotor activity and anxiety were investigated using the holeboard and plus-maze tests. In an 8 min holeboard test the lower (1.2 g/kg) dose increased both exploration and locomotor activity 0.5 h after ethanol administration whereas the higher (2.4 g/kg) dose decreased exploration but caused an even greater increase in locomotor activity. This activity increase was also seen 1 h post-administration. In the plus-maze test both doses showed an increased number of arm-entries 0.5 h and 1 h after administration but only the 2.4 g/kg dose caused anxiolytic effects persisting for over 2 h. The results add further support to the notion that the behavioral effects of ethanol vary with dose, time of administration and the behavioral measure taken. PMID- 2906445 TI - Is the discriminative stimulus produced by phencyclidine due to an interaction with N-methyl-D-aspartate receptors? AB - Rats were trained to discriminate phencyclidine (PCP) from saline at doses of 2 and 4 mg/kg, using a two-lever food reinforced operant technique. +/- N allylnormetazocine (+/- SKF 10047), +5-methyl-10,11-dihydro-5H dibenzo[A,D]cyclohepten-5,10-imine MK 801), 3-(2-carboxypiperazin-4-yl) propyl-1 phosphonic acid (CPP) and ifenprodil, which have been shown to antagonise the effects of N-methyl-D-aspartate (NMDA), were tested for their ability to give rise to PCP-appropriate responding. In rats trained at both doses of PCP, +/- SKF 10047 (2-12 mg/kg) and MK 801 (0.0125-0.2 mg/kg) produced dose-related responding on the lever associated with PCP injection. The relative potency of these two compounds was the same in the two groups of animals, but their absolute potencies to produce a PCP-like discriminative stimulus were dependent on the training dose of PCP. In contrast, neither the competitive NMDA antagonist CPP (4-20 mg/kg) nor the non-competitive antagonist ifenprodil (2-12 mg/kg) produced PCP-appropriate responding and ifenprodil (4 mg/kg) neither potentiated nor antagonised PCP. These findings are discussed in the light of the hypothesis that the behavioural effects of PCP are mediated via a reduction of neurotransmission at the NMDA subtype of glutamate receptors. PMID- 2906447 TI - Recent developments in neurobiology: Part III. Effectors of transmitter action. PMID- 2906448 TI - Psychoimmunological dysregulation in multiple sclerosis. PMID- 2906446 TI - Evidence that hypophagia induced by mCPP and TFMPP requires 5-HT1C and 5-HT1B receptors; hypophagia induced by RU 24969 only requires 5-HT1B receptors. AB - Male Sprague-Dawley rats deprived of food for 18 h were injected with the 5-HT agonists RU 24969, 1-(3-chlorophenyl)piperazine (mCPP) or 1-[3 (trifluoromethyl)phenyl)]piperazine (TFMPP) and 20 min later presented with their normal diet. Food intake was determined 1, 2 and 4 h later. All three drugs reduced intake over 1 and 2 h. Three out of four drugs with high affinity for 5 HT1C receptors (metergoline, mianserin, and mesulergine but not cyproheptadine) opposed hypophagia caused by mCPP. Another drug reported to have high affinity for the 5-HT1C site, 1-naphthyl-piperazine (1-NP), also blocked the hypophagic response to mCPP at doses which attenuated mCPP-induced hypolocomotion. Only one of the above drugs (metergoline) which also has high affinity for other 5-HT sites opposed hypophagia caused by RU 24969. Two out of three 5-HT1B receptor antagonists [(+/-) cyanopindolol, (-) propranolol, but not (-) pindolol)] which oppose hypophagia caused by RU 24969 (Kennett et al. 1987) also opposed hypophagia caused by mCPP. The 5-HT2 antagonists ketanserin and ritanserin, the 5 HT3 antagonist ICS 205-930 and the alpha 2 adrenoceptor antagonist idazoxan did not oppose the hypophagic effect of mCPP. In agreement with results for mCPP, hypophagia caused by TFMPP was opposed by both, mianserin and (+/-) cyanopindolol. Given alone, mianserin 1-NP and cyproheptadine but not ICS 205-930 increased food consumption of normally fed rats. The results suggest that RU 24969-induced hypophagia depends on 5-HT1B receptors but not on 5-HT1C receptors, while mCPP (and TFMPP)-induced hypophagia may depend on both receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2906449 TI - [Staff training in tropical medicine ]. PMID- 2906450 TI - Almitrine enhances in low dose the reactivity of pulmonary vessels to hypoxia. AB - Almitrine bismesylate (Alm) has been shown to increase arterial oxygen tension in patients with chronic obstructive pulmonary disease. This effect is though to be attributable to the enhancement of hypoxic pulmonary vasoconstriction (HPV). We evaluated the effect of various doses of Alm on HPV in terms of blood flow diversion associated with anoxic challenge to the left lower lobe (LLL) in dogs with the LLL and the rest of the lung separately ventilated. The stimulus response curve shifted to the right with increasing rate of Alm infusion, suggesting that Alm enhances the reactivity of the pulmonary vessels to hypoxia. Low doses of Alm enhanced HPV, while higher doses attenuated it. This suggests that the degree of vasoconstriction in hypoxic and non-hypoxic regions depends on the dose of Alm. The same effects of Alm were also observed in peripheral chemoreceptor denervated dogs. It is supposed that the vasoconstriction induced by Alm may be attributable to a direct effect on pulmonary vessels rather than to a nervous reflex effect. PMID- 2906451 TI - [Localized Zeek's angiitis of the small intestine. A case with surgical recovery]. PMID- 2906452 TI - Plasma and synovial fluid concentrations of sulphasalazine and two of its metabolites in rheumatoid arthritis. AB - A study was made of plasma and synovial fluid levels of sulphasalazine, one of its dissociation products--sulphapyridine and a metabolite of the latter--acetyl sulphapyridine in patients with rheumatoid arthritis (RA) who were in a steady state on sulphasalazine therapy. Combined sulphapyridine levels were significantly higher than those of sulphasalazine both in plasma and synovial fluid. Synovial fluid levels of both drugs correlated with their plasma levels and were generally slightly lower. Some patients accumulated sulphasalazine and sulphapyridine in the synovial fluid and the mean concentration of sulphasalazine was higher in the fluid than in the plasma. The explanation for this is uncertain. The concentration of combined sulphapyridine in synovial fluid was related to local joint inflammation and more active systemic disease. No consistent association was found between sulphasalazine levels and local or systemic activity. The higher sulphapyridine levels in synovial fluid found in this study suggest the possibility that this moiety could play a more active role in RA than it does in inflammatory bowel disease. PMID- 2906454 TI - Acid related disorders: a decade after the introduction of H2- receptor antagonists. Proceedings of an international symposium. Amsterdam, The Netherlands, 15 and 16 April 1988. PMID- 2906453 TI - Gastric acid and pepsin secretion after single oral doses of mifentidine in healthy subjects. AB - Mifentidine represents a potential improvement in the class of H2-receptor antagonists because of its long plasma half-life (10 h). The aim of this study was to evaluate the effects of mifentidine on pentagastrin-induced gastric pepsin and acid secretion in man. Nine healthy subjects participated in two separate sessions in which they were given randomly either a single oral dose of placebo or 10 or 20 mg of mifentidine, in accordance with an incomplete balanced block design. Basal secretion was measured 30 min before the administration of the drug, and 90 min later unstimulated gastric secretion was collected through a nasogastric tube for an additional 30 min. Then, 2 micrograms/kg/h pentagastrin were infused intravenously for 2 h, and gastric juice collected again in 15-min aliquots. Acid output was almost completely blocked by both doses of mifentidine during the unstimulated period (-99%). Pentagastrin infusion induced 10 times as much acid output as in the unstimulated phase. This dramatic increase was reduced by 32% with the low dose of mifentidine and to a major extent (-86%) with the high dose. The pepsin output was significantly inhibited by both doses of mifentidine during unstimulated (-83% and -82%) and stimulated (-49% and -71%) phases. Acid output correlated with the area under the mifentidine plasma levels (r = -0.69, p less than 0.05). It is concluded that mifentidine is a potent inhibitor of both acid and pepsin secretion in man. PMID- 2906455 TI - Pharmacokinetics of histamine (H2)-receptor antagonists, including roxatidine, in chronic renal failure. AB - In this paper the effects of chronic renal failure on the pharmacokinetics of H2 antagonists are reviewed and the results obtained with roxatidine presented. In normal renal function renal clearance is around 60-80% of total plasma clearance of all H2-antagonists. Consequently, prolongation of serum half-life, mainly due to a decrease in urinary excretion, is noted in patients with decreasing glomerular filtration rate. In chronic renal failure, a dose reduction is therefore necessary with all H2-antagonists, including roxatidine. It appears that neither haemodialysis nor peritoneal dialysis substantially influences the pharmacokinetics of these drugs. Therefore, the same dosage schedule as in uraemia may be applied in patients with dialysis. Finally, in the elderly the dosage of all H2-antagonists should be adapted to the expected decrease in renal function. PMID- 2906456 TI - Clinical characteristics of roxatidine acetate: a review. AB - Pharmacodynamic studies revealed that 150 mg of roxatidine acetate were optimal in suppressing gastric acid secretion, and that a single bedtime dose of 150 mg was more effective than a dose of 75 mg twice daily in terms of inhibiting nocturnal acid secretion. When administered orally as a capsule containing a granule formulation, the drug displayed modified-release properties, which led to a sustained suppression of gastric acid secretion. Clinical trials revealed that roxatidine acetate, 75 mg twice daily and 150 mg at night, was highly effective in healing duodenal and gastric ulcers and in reducing ulcer pain, over 4, 6, and 8 weeks of therapy. A steady reduction in diameter was observed in those ulcers not completely healed during therapy. The single bedtime dose regimen, while producing the same degree of healing as the divided daily dose during controlled clinical trials, may be of greater value in therapeutic use owing to improved patient compliance. In all efficacy criteria (cure, reduction in ulcer size, and pain relief) there was no significant difference between roxatidine acetate in a total daily dose of 150 mg, ranitidine in a total daily dose of 300 mg, and cimetidine in a total daily dose of 800 mg. Prevention of gastric and duodenal ulcer relapse was achieved by roxatidine acetate, 75 mg at night for 6 months, in about 70% of patients, as determined in open, pilot studies--a rate comparable to those reported for cimetidine and ranitidine. Roxatidine acetate shares with ranitidine an improved safety profile when compared with cimetidine. Human pharmacology studies and short-term and long-term clinical trials have all shown that roxatidine acetate is an exceptionally well tolerated compound, without the antiandrogenic activity and interference with hepatic drug metabolism which have characterized cimetidine treatment. A reason for the improved safety profile of roxatidine acetate may be its greater potency than cimetidine (six times less potent) and ranitidine (half as potent), so that lower doses of roxatidine acetate, representing a lower chemical load, are therapeutically effective. The novel structure of roxatidine acetate probably also underlies the improved safety of the compound. PMID- 2906457 TI - Inhibition of food-stimulated acid secretion (intragastric titration) by roxatidine acetate. Dose-response study. AB - In 10 healthy male volunteers a dose-response study was carried out with roxatidine acetate, 75, 150, 300, and 600 mg, and placebo on food-stimulated gastric acid secretion (intragastric titration (IGT]. The design of the study, with drug intake 150 min before starting IGT, enabled stable inhibition over the 90-min observation period of the test. Cumulative secretory results showed a dose related acid secretion inhibition (67% for 75 mg; 87.6% for 150 mg; 98.8% for 300 mg; 99.6% for 600 mg). The results were statistically significantly different from placebo and from each other, except for 300 mg versus 600 mg. With a Lineweaver-Burk plot, the ED50 was 41 mg and r = 0.98. Peak concentrations of roxatidine were observed either at T 150 or T 180. Significant correlation (r = 0.7; p less than 0.001) was obtained for the percentage inhibition with 75 mg and 150 mg together versus peak concentrations. Antisecretory potency with the IGT model applied to normal subjects appears to be of the same order for roxatidine acetate and for ranitidine. PMID- 2906458 TI - Assessment of intragastric acidity in man: modern aspects, reproducibility of intragastric pH-monitoring, and pharmacodynamic results obtained with H2-receptor antagonists. AB - Unlike other methods for assessing intragastric pH or total acid output, the reproducibility of ambulatory pH-monitoring is excellent but is critically dependent on the electrode system and the recording device. In three double-blind randomized studies in normal volunteers the effects of different dosage regimens of roxatidine acetate were compared with placebo and ranitidine. Roxatidine acetate, 75 mg twice daily, raised median 24-h gastric pH from 1.6 to 3.2 and median nocturnal pH from 1.5 to 3.0 Roxatidine acetate, 150 mg at bedtime, raised median 24-h pH to 2.4 and nocturnal pH to 5.9. Roxatidine acetate, 150 mg at bedtime, was as effective as ranitidine, 300 mg at night, in raising median nocturnal pH. However, when drugs were taken after the evening meal, 150 mg roxatidine acetate was less potent than 300 mg ranitidine or 300 mg roxatidine acetate. PMID- 2906459 TI - Penetration of roxatidine into the cerebrospinal fluid. AB - Central nervous system side effects are occasionally associated with the administration of H2-receptor antagonists. There seems to be a direct correlation between the occurrence of side effects such as mental confusion and the drug concentration in the cerebrospinal fluid. In animal experiments the new H2 blocker roxatidine did not cross the blood-brain barrier. We therefore investigated the penetration of roxatidine into human cerebrospinal fluid (CSF). Nine healthy subjects scheduled for elective spinal anesthesia were premedicated with 150 mg roxatidine orally. Blood samples were taken at 30-min intervals for up to 6 h. A 2-ml CSF sample was taken from each patient at the time of spinal puncture. Small amounts of roxatidine were detectable in the CSF, the CSF to plasma ratio ranging from 0 to 0.89. PMID- 2906460 TI - Recent developments in peptic ulcer treatment. AB - Since peptic ulcer disease is a multifactorial disease, the ideal therapeutic approach would be to use different drugs for different ulcers. In the past few years some studies have been published suggesting that subgroups of patients with peptic ulcer might particularly benefit from specific forms of therapy. In the present report the available evidence has been critically reviewed. PMID- 2906461 TI - Is chronic long-term inhibition of gastric secretion really dangerous? AB - Powerful gastric secretion inhibitors produce cancer in their target organ, the stomach, in experimental animals. The possible mechanisms of the carcinogenic effect are discussed under the headings of the potential noxious change in the gastric luminal contents, as is the possibility that the drugs act as epigenetic or genotoxic carcinogens. Whatever the mechanisms of the drug-induced carcinogenesis, it is clear that there is a toxicologic hazard, which must be assessed rationally and not by means of sophistry. Until the dangers posed by powerful gastric secretory inhibitors to man have been better evaluated, these drugs must not be used for treatment other than of patients with gastrinomas. PMID- 2906462 TI - Future trends in the management of peptic ulcer disease. AB - Future trends in the short- and long-term management of peptic ulcer disease are considered. The present state of development of pharmacologic agents for the short-term healing of duodenal and gastric ulcer is impressive, and high rates of healing with rapid symptom relief can be safely achieved with several agents. The problem of ulcer recurrence has not been solved, although new work concerning the role of Campylobacter pylori holds promise. The mortality of acute gastrointestinal haemorrhage remains unacceptably high, especially in the elderly. Therapeutic endoscopy may be effective in decreasing the death rate from bleeding. PMID- 2906463 TI - H2 antagonists in the treatment of upper gastrointestinal bleeding. AB - It is plausible that, for pharmacologic and physiologic reasons, antisecretory treatment reduces the chances of rebleeding from gastric and duodenal ulcers and thereby reduces operation and death rates. Currently available evidence is not strong enough to confirm this, in part because trials have been too small to detect any differences present, and perhaps in part because drug doses have been too low to achieve the desired antisecretory potential. PMID- 2906464 TI - Peptic ulcer disease in the elderly. AB - The elderly are a growing minority; they comprise approximately 12% of the population but consume an increasing proportion of health care resources. Disease in the aged is unique in many ways, demanding special attention and study. This is particularly evident with regard to peptic ulceration, which is a more serious disorder in the elderly than in younger individuals, often presenting in an atypical manner and having a greater propensity to complications. Management traditionally tends to be conservative, enthusiasm often being tempered by the presence of frailty and associated disease. Despite technologic and pharmacologic advances, the elderly continue to account for a disproportionate number of deaths from this disorder. This paper will review the peculiarities of peptic ulcer disease of the elderly and examine currently emerging trends which may influence evolving management policies. PMID- 2906465 TI - Treatment of reflux oesophagitis with H2-receptor antagonists. AB - The important therapeutic value of H2-receptor antagonists for the treatment of patients with reflux oesophagitis has been demonstrated beyond doubt. A large number of patients have been treated with cimetidine or ranitidine in controlled as well as open short-term studies. Mild to moderately severe reflux oesophagitis heals effectively when H2-receptor antagonists are prescribed for a sufficient time period, preferentially 12 weeks. The more severe forms of oesophagitis, however, need more profound acid suppression, with potent H2-receptor antagonists, addition of prokinetic agents, or treatment with H+/K+ATP-ase antagonists. Omerpazole has proven to be of high efficacy, particularly in the management of severe reflux oesophagitis. Data on long-term treatment with H2 receptor antagonists, to prevent recurrences after healing, are not reassuring: long-term low-dose H2-receptor antagonist therapy is not effective, and trials should be undertaken with higher doses of H2-receptor antagonists, more potent antagonists, or with combinations of antagonists and prokinetics. In these studies, 24-h intraoesophageal and intragastric pH measurements should be incorporated, to detect more accurately time periods of nonsuppressed acid secretion. Such studies will undoubtedly better define the therapeutic place of the presently available and forthcoming H2-receptor antagonists. PMID- 2906466 TI - Economic assessment of peptic ulcer disease treatments. AB - The cost and economic outcomes of peptic ulcer disease (PUD) treatments are important but uncommonly assessed by clinical researchers in gastroenterology. There is a growing interest in these assessments because of their implications for patient management and health care planning. Also, cost assessments offer the clinical researcher a powerful method to analyze the socioeconomic impact of different therapies in randomized prospective studies. The purposes of this paper are 1) to present methods and results of cost and economic assessment of PUD and 2) to consider the impact of H2 receptor antagonists on PUD cost. As with any chronic disease, PUD has direct and indirect costs. Direct costs are for hospital and clinic care, physicians' and surgeons' services, pharmacy fees, and nursing home care. Indirect costs of PUD affect society and include costs of absenteeism from work, disability, and mortality. Direct and indirect costs can be estimated prospectively in short-term and maintenance PUD clinical research studies. Several cost and economic analyses of PUD have been reported by clinical investigators and medical economists of different countries. They report a significant change in the direct and indirect costs of peptic ulcer treatment after the introduction of the H2 receptor antagonists. PMID- 2906467 TI - Regulation of receptors on parietal cells on acid secretion. AB - Four types of receptors have so far been identified on the parietal cell: receptors for gastrin, acetylcholine, and histamine, whose activation leads to stimulation of acid secretion, and receptors for prostaglandins of the E series, whose activation leads to inhibition of acid secretion. Postreceptor events following drug-receptor interaction include mobilization of calcium ions and cAMP formation. Moreover, a number of putative receptors (for somatostatin, CCK, adenosine, secretin, etc.) have been hypothesized, even though definite evidence is still lacking. Finally, other substances may influence gastric acid secretion in a positive or negative way, but no evidence for an involvement of specific receptors on the parietal cells is available so far. PMID- 2906468 TI - Prostaglandin treatment for peptic ulcer. AB - Prostaglandin analogues have been expected to outperform other antisecretory drugs as ulcer healing agents. This expectation arises from their ability to combine 'cytoprotection' with gastric secretory inhibition. Evidence of the existence of these two separate functions abounds in animals and in humans, but a clinical advantage has not evolved. Whereas most clinical trials show no difference between prostaglandin analogues and H2-receptor antagonists, some studies have shown the prostaglandins to be significantly less effective or no better than placebo. The role of cytoprotection in ulcer healing (as opposed to prevention) may be questioned and the present clinical role for these agents is unclear. PMID- 2906469 TI - Hormonal regulation of gastric acid in peptic ulcer disease. AB - Although the pathogenetic role of gastrin in gastric acid hypersecretion and peptic ulcer is well established in a number of uncommon disorders, such as Zollinger-Ellison syndrome, antral G-cell hyperfunction, and retained, excluded antrum after subtotal gastrectomy, the significance of hormonal abnormalities in normogastrinaemic peptic ulcer is less obvious. Most studies have pointed to an impaired feedback mechanism between gastric acid and antral gastrin secretion in duodenal ulcer disease, possibly due to antral somatostatin deficiency. Furthermore, antisecretory drugs may induce abnormalities of gastrointestinal hormones. Potent antisecretory drugs, such as omeprazole, increase serum and antral gastrin and reduce antral somatostatin, whereas certain prostaglandin E2 analogues inhibit serum gastrin secretion after feeding. PMID- 2906470 TI - Chemical and biologic differences between various H2-receptor antagonists. AB - After a brief historical review, the common chemical features of various H2 receptor antagonists are discussed, demonstrating that an imidazole, furan, thiazole, and the piperidinylmethylphenoxy moiety can serve as an aromatic nucleus of histamine H2-receptor antagonists. Furthermore, it is paradigmatically illustrated that the histamine H2-receptor antagonists in use or under clinical investigations inhibit, in a competitive and surmountable manner, parietal cell acid secretion and histamine H2-receptor-linked adenylate cyclase. Furthermore, toxicologic problems of unsurmountable and/or or long-acting histamine H2 receptor antagonists (tiotidine, loxtidine, and SK&F 93479) are discussed. PMID- 2906471 TI - Chemical and biologic characteristics of roxatidine acetate. AB - Roxatidine acetate is a specific and competitive H2-receptor antagonist, as shown in isolated rabbit gastric glands or guinea pig atria preparations. The antisecretory effect of roxatidine acetate is mediated by its main metabolite, roxatidine. In the rat, roxatidine acetate was equipotent after intraduodenal and intraperitoneal administration, indicating excellent bioavailability. Roxatidine acetate and roxatidine were equipotent in the rat after intravenous administration. In the Heidenhain-pouch dog stimulated by food ingestion or maximal histamine dosing, roxatidine acetate and roxatidine proved to be 3-6 times more potent than cimetidine in inhibiting gastric acid secretion. From in vitro experiments it can be concluded that roxatidine acetate and ranitidine are equipotent. Roxatidine acetate has no antiandrogenic effects and does not influence drug-metabolizing enzymes in the liver. PMID- 2906472 TI - Therapeutic approach in patients with concomitant disease/drug--drug interactions (roxatidine acetate). AB - Possible mechanisms of drug interactions with H2-antagonists are outlined. The mode of action of roxatidine acetate on hepatic microsomal enzymes is contrasted with those of cimetidine and ranitidine, and their differing structure-activity relationships are discussed. In the light of the mechanisms of drug interactions with H2-antagonists, clinical studies with roxatidine acetate are contrasted with published interaction data of cimetidine and ranitidine. The therapeutic consequences of these data are considered. PMID- 2906473 TI - Pharmacokinetics of olsalazine and its metabolites. AB - After a single dose of olsalazine, the maximum serum concentration of the intact compound is much lower than after an equivalent dose of sulphasalazine. In both compounds the diazo bond is largely split by colonic bacteria and comparable amounts of the metabolites 5-ASA and acetyl-5-ASA are recovered in the faeces. During long-term ingestion of olsalazine, 1-4 weeks are required to reach a steady state, and serum concentrations of the parent drug are low. It is demonstrated that olsalazine is rapidly sulphated into the metabolite, olsalazine O-sulphate, which has a long half-life. Acetyl-5-ASA is more stable and more soluble than 5-ASA; however, the therapeutic efficacy of acetyl-5-ASA in inflammatory bowel disease is not proven. PMID- 2906474 TI - Olsalazine in the treatment of ulcerative colitis among patients intolerant of sulphasalazine: a prospective, randomized, placebo-controlled, double-blind, dose ranging clinical trial. AB - Sixty-six outpatients with active ulcerative colitis who were intolerant of sulphasalazine were treated in a double-blind randomized trial with placebo or olsalazine in daily doses of 0.75, 1.5, or 3 g. Overall, 35% of patients receiving olsalazine improved clinically, compared to 16% of patients receiving placebo. Statistically significant or nearly significant improvement was demonstrated in colitis activity by the end compared to the beginning of the study within the combined olsalazine group and within patient groups receiving olsalazine at daily doses of 1.5 g and 3 g. There were no differences between the treatment and placebo groups for any of the reported adverse effects or laboratory variables. The data suggest that olsalazine is effective for the treatment of ulcerative colitis and is well tolerated among patients intolerant to sulphasalazine. PMID- 2906475 TI - Evolution of olsalazine. AB - Sulphasalazine was first produced nearly 50 years ago through the inspiration of a Swedish doctor, Dr Nanna Svartz. Later, in controlled trials, this compound was shown to reduce substantially the frequency of recurrent attacks of ulcerative colitis when used as long-term maintenance therapy. Studies into the metabolism of sulphasalazine have shown that, when taken orally, most of the ingested dose reaches the colon intact, and within the colonic lumen, bacteria split sulphasalazine into two breakdown products, sulphapyridine and 5-ASA. 5-ASA was shown to be the active therapeutic moiety while sulphapyridine served simply as a carrier. Olsalazine was developed to retain the property of sulphasalazine of reaching the colon intact, but also to liberate two molecules of 5-ASA with no residual carrier. PMID- 2906476 TI - Double-blind comparison of olsalazine and sulphasalazine in active ulcerative colitis. AB - Fifty-six patients with ulcerative colitis of mild to moderate severity were entered into a randomized, double-dummy comparison of sulphasalazine, 3 g/day, with olsalazine, 3 g/day. Patients were assessed clinically, and by sigmoidoscopy and biopsy, on entry and at 5 weeks. Both agents produced a similar reduction in stool frequency and in the passage of blood and mucus. Improvements in sigmoidoscopic and histological appearances of the rectal mucosa were observed to a similar extent in both groups of patients. Two patients treated with olsalazine were withdrawn because of increased diarrhoea attributable to the medication. Two patients given sulphasalazine for the first time developed a skin rash. Other side-effects seen during the trial were mild. In this small short-term study, oral olsalazine appeared to be as effective as sulphasalazine in the treatment of mild to moderate ulcerative colitis. PMID- 2906477 TI - Controlled trial comparing olsalazine and sulphasalazine for maintenance treatment of ulcerative colitis. AB - Olsalazine and sulphasalazine were compared in a double-blind, double-dummy trial in the prevention of relapse of ulcerative colitis over 6 months. The majority were taking sulphasalazine. They were randomized to receive either olsalazine, 500 mg b.d., or sulphasalazine, 1 g b.d. Of 82 patients, 16 relapsed on olsalazine compared with 10 of 82 on sulphasalazine. This difference was not statistically significant (p = 0.16). Twenty-one patients reported adverse events in the olsalazine group, of whom 16 were withdrawn, while 20 patients reported adverse events in the sulphasalazine group, with 9 of them being withdrawn. The differences were not statistically significant. No major haematological or biochemical abnormalities occurred. Thus, olsalazine is similar to sulphasalazine for the prevention of relapse of ulcerative colitis. PMID- 2906478 TI - Disposition of 5-aminosalicylic acid by 5-aminosalicylic acid-delivering compounds. AB - Time-related urinary excretion and faecal excretion of 5-ASA and acetyl-5-ASA were measured in eight healthy volunteers after a single oral dose of the azo compounds sulphasalazine and olsalazine, the slow release compounds Pentasa, Asacol and Salofalk, and plain 5-ASA. After ingestion of both azo compounds and slow-release compounds, urinary excretion of 5-ASA was markedly delayed and reduced, and faecal excretion was enhanced. At all points of time, there was a significant, but not very marked difference in urinary excretion of 5-ASA after ingestion of the azo compounds and the slow-release compounds, in favour of the azo compounds. A significantly larger proportion of the ingested 5-ASA, moreover, was excreted in faeces after the intake of azo compounds as compared with slow release compounds. PMID- 2906479 TI - Treatment of ulcerative colitis with olsalazine and sulphasalazine: efficacy and side-effects. AB - The effects of olsalazine were studied mainly in patients with ulcerative colitis who were intolerant to sulphasalazine, and for relapse prevention. A crossover design with sulphasalazine, 3 g/day, and olsalazine, 1.5 g/day, was applied to compare the side-effects of each drug and to evaluate their therapeutic efficacy. A total of 41 patients with mild or moderately severe left-sided colitis or proctitis were assigned to a randomized treatment schedule. Olsalazine and sulphasalazine were similar in their therapeutic efficacy. Twelve patients complained of adverse effects while on sulphasalazine and 4 patients during olsalazine treatment (p less than 0.05). It is concluded that olsalazine is a safe and effective drug for the treatment of mild or moderately severe ulcerative colitis, and is comparable to sulphasalazine, though with reduced side-effects. PMID- 2906480 TI - Different proliferative activity in vitro of periportal and perivenous hepatocytes. AB - The different growth potentials of hepatocytes from different zones of the liver acinus were assessed in vitro by autoradiography with immunocytochemical discrimination of periportal and perivenous hepatocytes by the marker enzyme glutamine synthetase (GS) or their direct isolation by the digitonin/collagenase perfusion technique. All stimuli studied led to much higher labeling indices in GS-negative than in GS-positive cells in cultures both of all hepatocytes and of the perivenous subfraction. In contrast, the response of GS-negative hepatocytes in the periportal and in the perivenous subfractions differed only gradually depending of the growth stimulus. It is concluded that GS-positive hepatocytes are distinguished from all other hepatocytes by a completely different growth characteristics, which may play a dominant role in the regenerative remodelling of zone 3. The wave-like spatiotemporal pattern of DNA synthesis during liver regeneration, however, seems to be due to gradual changes in growth responsiveness of the hepatocytes along the acinus. PMID- 2906481 TI - Laser Doppler flowmetry estimating myocardial perfusion after internal mammary artery grafting. AB - Myocardial perfusion in the anteroapical part of the left ventricle was monitored intraoperatively with laser Doppler flowmetry in ten patients after grafting of the internal mammary artery to the left anterior descending artery. The myocardial perfusion after declamping of only the mammary artery averaged 61% of the perfusion found after declamping also the aorta. Laser Doppler flowmetry is proposed to offer a means of monitoring regional myocardial perfusion in the phase immediately after internal mammary artery grafting. PMID- 2906482 TI - A study of bancroftian filariasis on the islands of Batan and Rapu Rapu, Philippines. AB - The islands of Batan and Rapu Rapu in southeastern Luzon, Philippines, were surveyed for filariasis from November 1984 to May 1985. Microfilariae of Bancroftian filariasis were detected in 10.5% of the people over one year of age. Microfilarial rates and intensity of infection were the same for males and females. The highest rates for both sexes were in the 56- to 60-year-old age group. Aedes poicilius, which breeds in abaca and banana plants, was found to be very anthropophilic, comprising 96.5% of the mosquitoes biting man. This mosquito bites most frequently in the middle of the night. Dissections showed that 1.0% of Ae. poicilius were infective with third-stage larvae, and each infective mosquito contained a mean average of 5.6 larvae. PMID- 2906483 TI - A study of dispersal, survival and gonotrophic cycle estimates of Mansonia uniformis in an open swamp ecotype. AB - Five mark-release-recapture experiments with wild caught Ma. uniformis were conducted in an open swamp area at Batang Berjuntai in Selangor, 40 km from Kuala Lumpur, Malaysia, between May 1983 and January 1985. A total of 64 (0.14%) from the 45,950 females released were recaptured feeding on humans and cattle and resting in cattle-sheds. Substantially fewer (0.03% to 0.09%) females were recaptured from releases of blood-fed females than from releases of unfed females (0.20% to 0.23%). More than 70% of all recaptures were taken within a radius of 1.5 km around the point of release and the longest detected flight was 3.5 km. The mean dispersal distance for blood-fed and unfed females was 1.445 +/- 1.06 and 1.706 +/- 1.03 km, respectively. However, there was no significant difference in the overall mean dispersal of the two groups of females (p greater than 0.05). The duration of the gonotrophic cycle in the field was between 3 to 4 days. Daily survivorship estimates (0.783-0.867) based on the recapture rates of date specific marked females was comparable to that estimated vertically from the dissection of unmarked females (0.751-0.795). These experiments revealed the remarkable flying ability of Ma. uniformis and the importance of reinvasion must be recognized when control operations are restricted to small areas. PMID- 2906484 TI - [Neurohumoral regulation of gastric secretion in stomach and duodenal ulcers]. PMID- 2906485 TI - [Drug therapy and therapeutic tactics in gastroduodenal ulcer]. PMID- 2906486 TI - [Arrhythmic syndrome and sudden death in hypertrophic cardiomyopathy]. PMID- 2906487 TI - [Importance of urinary enzymes in the monitoring of drug nephrotoxicity]. PMID- 2906488 TI - [Beta-adrenergic hypertonia in psychosomatic manifestations of anxiety and the therapeutic effect of a cardioselective beta-blockader: betaxolol]. PMID- 2906489 TI - Crystal structure, thermal behaviour, protonation and mass spectroscopic studies of racemic 4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole hydrochlorides. AB - The crystal structure, thermal behaviour, mass spectrum and protonation of 4-[1 (2,3-dimethylphenyl)ethyl]-1H-imidazole (medetomidine) hydrochloride have been investigated. The title compound crystallizes in both hydrated and anhydrous forms, and their structures have been determined by three-dimensional X-ray structure analysis. The crystals of the anhydrous form are monoclinic and those of the hydrated form (containing one hydrate water molecule) are triclinic with unit-cell dimensions: a = 23.861(9), b = 7.721(4), c = 22.037(9) A, beta = 140.20(4) degrees, Z = 8, and space group C2/c, and a = 7.841(4), b = 8.380(3), c = 12.743(6) A, alpha = 93.66(3), beta = 102.90(3), gamma = 116.85(3) degrees, Z = 2, and space group P1, respectively. Thermal decomposition of the title compound has been interpreted from the TG, DTG and DSC curves with the help of mass spectrometry. Medetomidine hydrochloride monohydrate decomposes in four stages. The first is dehydration at 45-100 degrees C, the second is evaporation of HCl and medetomidine base at 200-320 degrees C, and the third and fourth are decomposition at 340-570 degrees C. The protonation constant is 7.04 in aqueous 0.1 M NaClO4 (25 degrees C). PMID- 2906490 TI - Gastroduodenal physiology in relation to peptic ulcer disease. PMID- 2906491 TI - Regulatory peptides and their pathophysiologic role in peptic ulcer disease. PMID- 2906492 TI - Treatment of recurrent ulceration after vagotomy for duodenal ulcer. PMID- 2906493 TI - Medical treatment of peptic ulcer disease. AB - Only a decade ago surgery was the preferred treatment of recurrent peptic ulcer. With the introduction of cimetidine in 1976 effective and safe medical treatment could be offered to the patient. H2-receptor antagonists are still the basic drugs in ulcer healing, but in recent years mucosa protective agents as sucralfate and colloidal bismuth have been increasingly used. Complete inhibition of acid secretion may be achieved by the new proton pump inhibitor omeprazole. In ulcer resistant to treatment with H2-receptor antagonists either a mucosa protective agent, as colloidal bismuth or a potent acid inhibitor (omeprazole) may be used. In recurrent duodenal ulcer a systematic and prolonged maintenance therapy with H2-receptor antagonists is indicated. This treatment is safe and it reduces the incidence of a relapse to one third compared with placebo. Surgery is no longer indicated in the majority of patients with uncomplicated recurrent peptic ulcer. In most patients this disease can now be controlled by effective and cheap anti-ulcer drugs. Although medical treatment of peptic ulcer has been used for centuries, surgery was still the main treatment of recurrent peptic ulcer in the nineteen seventies. Up to that time the surgical management of ulcer disease had made major progress, while medical treatment had failed to offer effective cure. Thus, as late as in 1975 the medical treatment of peptic ulcer consisted of antacids, bed rest and carbenoxolone. With the important side effects of carbenoxolone in mind, it is no wonder that medical treatment was no alternative to surgery in patients suffering from recurrent peptic ulcer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2906494 TI - Lymphocytes subset in hyperandrogenic women with polycystic ovarian disease. AB - The correlation between the sex steroids and the immune system is already known but the relationships between testosterone, progesterone, estradiol, cortisol and the immune system are still controversial. The Authors have studied lymphocytes subset in ten women with polycystic ovarian disease (PCOD); it was observed: 1) a decrease of T8 in 64% and of natural killer activity (NK) in 60% of patients, and an increase of T4/T8 ratio in 55%; 2) a significant negative correlation between androstenedione and testosterone (P less than 0.05); 3) a significant positive correlation between the decreased T8 lymphocytes and NK cells and the increase of testosterone and androstenedione serum values. The data suggest that in PCOD a correlation between endocrine and immune system exists and the androgens can affect the lymphocyte subset. PMID- 2906495 TI - Application of immunohistochemistry to the isolated mucosa of the mouse gastrointestinal tract, with special reference to somatostatin cells. AB - In the present study, in order to easily grasp whole images of somatostatin (D) cells, the isolated mucosa of the mouse gastrointestinal tract was immunohistochemically treated. The present study revealed that: (1) in the stomach, small-intestinal villi and colon, about 20% of the D cells extrude basal cytoplasmic processes, showing terminal expansions in many cases; on the other hand, in the crypts of the small intestine, few D cells possess basal processes, and (2) in the stomach, there is no determined tendency in the direction of the basal processes of the D cells; on the other hand, in the small-intestinal villi and colon, most D cell basal processes run toward the villus base and colon crypt bottoms. The direction of the basal processes of the D cells in the gastrointestinal tract seems to be mostly in favor of the migration pattern of epithelial cells described previously. It is likely that, if the targets of the D cells are near the D cells, the basal process is not necessary for local secretion of somatostatin. During migration, however, D cells might extrude basal processes to keep relationships with their targets. PMID- 2906496 TI - Effects of taxol on endothelial cells of the developing semilunar heart valves in the chick embryo. AB - Recent ultrastructural studies have revealed that there are differences in endothelial cell shape and cytoskeletal architecture between the arterial and ventricular faces of developing semilunar valves. In the present work we have analyzed valvular endothelial cell response to taxol in the chick embryo. Following taxol administration, abnormal mitotic cells appear in the endothelium of both faces of the cusps. Interphase cells show few structural alterations. No differential response of the valvular endothelium to the drug was observed in the arterial or ventricular faces of the cusps. PMID- 2906497 TI - Nephropathia epidemica encephalitis. AB - A case of serologically proven Nephropathia epidemica (NE) with encephalitis is described. Follow up of serum and CSF antibody titres demonstrated NE virus antibody production in the CNS concomitantly with clinical encephalitis. Decrease of initially high CSF antibody titres was followed by a simultaneous increase of serum antibody titres corresponding to the clinical picture shifting from encephalitis to nephritis. This suggests that the first replication of NE virus may undertake in the CNS. PMID- 2906498 TI - Effect of renal venous pressure elevation on tubular sodium and water reabsorption in the dog kidney. AB - This study was performed in order to quantify the effects of renal venous pressure (RVP) elevation on absolute and fractional reabsorption rates of sodium and water in proximal and distal segments of the nephron in dog kidneys. Renal blood flow (RBF) was measured electromagnetically. Clearance of [51Cr]EDTA was used as a measure of the rate of glomerular filtration (GFR). GFR, urinary excretion rates of sodium and water, and lithium clearance were used for assessing the absolute and fractional reabsorption rates of sodium and water in the proximal as well as in more distal segments of the nephron. In the kidneys with intact innervation RVP elevation to 19.9 +/- 0.1 mmHg caused significant increases in both absolute (APR) and fractional (FPR) proximal reabsorption rates from 33.4 +/- 4.2 to 38.7 +/- 2.0 ml min-1 and from 0.62 +/- 0.04 to 0.71 +/- 0.04, respectively. These responses were unaffected by acute surgical denervation of the kidneys. In contrast, chronic renal denervation or infusion of phentolamine (5 micrograms kg-1 min-1) into the renal artery eliminated the increase in APR and FPR during RVP elevation to 20 mmHg. Chronic, but not acute renal denervation depleted renal tissue content of adrenaline and noradrenaline. The results suggest that the increase in APR and FPR during RVP elevation is due mainly to local sympathetic reflex mechanisms. PMID- 2906499 TI - Effects of pancreatic noradrenaline infusion on basal and stimulated islet hormone secretion in the dog. AB - We investigated the direct pancreatic effects of noradrenaline in vivo on the secretion of insulin, glucagon, and somatostatin from the in situ pancreas in halothane-anaesthetized dogs. Noradrenaline was infused into the superior pancreatic artery at 12 ng min-1, a rate that did not alter systemic glucose or noradrenaline levels nor heart rate or blood pressure. This pancreatic infusion of noradrenaline did not affect the basal pancreatic output of insulin, yet did markedly inhibit arginine-stimulated insulin secretion. The acute insulin response (AIR) to an intravenous injection of arginine (2.5 g), which was 4293 +/ 1260 microM min-1 under control conditions, was reduced to 1054 +/- 396 microU min-1 by noradrenaline (P less than 0.01). Noradrenaline increased basal pancreatic glucagon output from 321 +/- 130 pg min-1 to 876 +/- 309 pg min-1 after 20 min of infusion (P less than 0.05) and the acute glucagon response (AGR) to arginine, being 1033 +/- 203 pg min-1 under control conditions and 1746 +/- 249 pg min-1 during noradrenaline infusion (P less than 0.05). The basal output of somatostatin did not change during noradrenaline infusion, but arginine stimulated somatostatin secretion was impaired. The acute somatostatin response (ASLIR) to arginine was 473 +/- 124 fmol min-1 under control conditions and was decreased to 140 +/- 80 fmol min-1 by noradrenaline (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2906500 TI - Chronic uridine treatment reduces the level of [3H]spiperone-labelled dopamine receptors and enhances their turnover rate in striatum of young rats: relationship to dopamine-dependent behaviours. AB - The effect was studied of chronic uridine treatment on the recovery of striatal D 2 dopamine (DA) receptors after their irreversible blockade by N-ethoxycarbonyl-2 ethoxy-I,2-dihydroquinoline (EEDQ) in young (40 days old) and adult (14 months old) male rats using [3H]spiperone as radioligand. Chronic uridine treatment (15 mg kg-1 day-1, i.p., 14 days) causes a reduction of [3H]spiperone binding sites in striatum of young rats. This treatment also produces an increase in the rate of recovery of striatal [3H]spiperone-labelled DA receptors in young, but not in adult rats. Catalepsy and exploratory locomotor activity, two behaviours associated with blockade versus activation of DA receptors, were evaluated in the same rats. The behavioural recovery from the EEDQ-induced syndrome is more rapid in the young rats treated with uridine than in the saline-treated group. The behavioural recovery in old rats was not affected by chronic uridine treatment. Thus, in young rats the pyrimidine nucleoside uridine may modulate the steady state and the turnover rate of striatal D-2 DA receptors. PMID- 2906501 TI - Temporal relationship of contractility and myocardial potassium balance following beta-adrenergic stimulation of the in situ pig heart. AB - Lower intracellular Na+ during beta-adrenergic stimulation provides an increased driving force for Na-Ca exchange, which might attenuate the inotropic response. Since (1) Na+ reduction is coupled to K+ uptake, and (2) K+ uptake lags behind the positive inotropic response to isoproterenol, we could examine the effect of Na-Ca exchange by comparing cardiac contractility and K+ balance following intracoronary isoproterenol infusion (0.6-0.8 microgram min-1). In 8 open-chest pigs, potassium concentrations were continuously measured by PVC-valinomycin mini electrodes in arterial blood (a), and in myocardial venous blood in a shunt from the coronary sinus (cs) to the right atrium. Shunt flow, aortic flow, a left ventricular segment length and left ventricular pressure (LVP) were also continuously recorded. 64 (41-85)% (median and 95% confidence interval) of the LV dP/dt increase occurred within 1 min; thereafter contractility rose slowly. During the first minute of isoproterenol infusion, there was a small net myocardial K+ release, which then reversed to K+ accumulation. A maximum a-cs K+ concentration difference of 0.20 (0.09-0.39) mM occurred at 3.0 (2.0-4.25) min, falling to 0.05 (0.01-0.10) mM after 6.5 (3.75-8.75) min, at which point accumulated myocardial K+ uptake was 135 (27-219) mumol 100 g-1. Heart rate remained unchanged and intramural ECG indicated no sign of ischemia during the first 1.5 min of isoproterenol infusion. At 6.25 (5.0-8.0) min after stop of isoproterenol, LV dP/dt was 12 (9-24)% lower than before infusion (P less than 0.02) whereas myocardial K+ content remained higher than control. Thus, the monovalent cation shift succeeding the positive inotropic response was not associated with reduced contractility, but could explain the undershoot of LV dP/dt after stopping isoproterenol. PMID- 2906502 TI - Reduction of [3H]nicotine binding by clonidine in membrane preparations of the rat cerebral cortex. PMID- 2906503 TI - Baroreflex control of jejunal blood flow and fluid transport in cats; effects of yohimbine, an alpha 2-adrenergic antagonist. AB - The aim of the study was to test the hypothesis that baroreceptor unloading increases jejunal fluid absorption rate via an alpha 2-adrenergic effect on electrogenic active transport. In 13 chloralose-anaesthetized cats, the carotid sinus baroreceptors were isolated and perfused with arterial blood, and we studied the effects of a graded decrease in carotid sinus pressure on intestinal vascular resistance, net fluid absorption rate and the potential difference between the intestinal lumen and the peritoneal cavity (PD). Experiments were performed in seven control animals and in six animals pretreated with yohimbine, an alpha 2-adrenergic antagonist, at a dose of 0.1 mg kg-1 i.v. Yohimbine per se had no significant effects on systemic arterial pressure, intestinal vascular resistance, net fluid absorption rate or PD. In the control animals, baroreceptor unloading induced an increase in systemic arterial pressure, intestinal vascular resistance and net fluid absorption rate, and a decrease in the PD. Yohimbine pretreatment did not significantly affect the systemic blood pressure response to baroreceptor unloading, but abolished the effect on intestinal vascular resistance and PD. After yohimbine treatment, decreases in carotid sinus pressure still enhanced net fluid absorption rate, but this response was observed in a higher range of carotid sinus pressures than in control animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2906504 TI - Both DA1 and DA2 receptor agonists are necessary to inhibit NaKATPase activity in proximal tubules from rat kidney. PMID- 2906505 TI - Noradrenaline as a possible mediator in the renal response to vascular expansion with blood in the cat. AB - In chloralose anaesthetized cats with renal arterial pressure kept constant at 100 mmHg, vascular expansion with precirculated blood, 20 ml kg b.w.-1, caused significant increments in arterial inflow rates of blood to the deep (ARBFD) and superficial (ARBFS) renal venous drainage area of 35 +/- (SE)10 and 19 +/- 6%, respectively, and in the excretion rates of water and sodium of 73 +/- 24 and 75 +/- 28%, respectively, while GFR remained essentially unchanged. In acutely denervated kidneys the responses to expansion were not significantly different from those of innervated kidneys, which indicated largely humoral mediation. Arterial plasma concentrations of noradrenaline, adrenalin, and vasopressin fell significantly to values of a half to one-third of pre-expansion values, while plasma dopamine was not significantly changed by expansion. The response to expansion could be (1) reversed by a 'substituting' intraaortic infusion of noradrenaline, and (2) imitated, without volume expansion, by an infusion of an alpha-adrenergic blocking agent (phentolamine). It is concluded that the renal response (excretory and vascular) to volume expansion with blood is largely humorally mediated and that circulating noradrenaline may play a causal role in the response. PMID- 2906506 TI - Brain-gut peptides in sauna-induced hyperthermia. AB - The release of brain-gut peptides during sauna bathing was studied in seven women. All women underwent a 20 min sauna bath. Their sublingual temperature rose from 36.9 +/- 0.1 degrees C to 38.6 +/- 0.2 degrees C (mean +/- SEM). A significant increase in circulating plasma vasoactive intestinal polypeptide (VIP) was observed during heat exposure, whereas plasma pancreatic polypeptide (PP), motilin and blood glucose rose and stayed significantly elevated first during the ensuing 60 min (P less than 0.05 in all cases). A similar increase in plasma insulin failed to reach statistical significance, whereas the plasma levels of somatostatin and cholecystokinin (CCK) remained unchanged. It is suggested that the plasma VIP levels are related to compensatory mechanisms during heat exposure with vasodilatation and heat loss. PMID- 2906507 TI - Intraluminal prostaglandin E2 affects gallbladder function by activation of intramural nerves in the anaesthetized cat. AB - Gallbladder mucosal net fluid transport and motility were measured in vivo by a continuous perfusion technique in the anaesthetized cat. Prostaglandin E2, administered to the perfused gallbladder lumen, caused a contraction decreasing gallbladder volume capacity, and induced a secretory response by the mucosa. These effects by prostaglandin E2 were abolished by the nerve-blocking agent tetrodotoxin (administered close intraarterially) and somatostatin (administered intravenously), but not by intravenous hexamethonium. Atropine (administered intravenously) reduced the order of magnitude of the gallbladder contraction in response to prostaglandin E2 but did not affect the secretory response by the mucosa. Neither of these drugs significantly affected gallbladder volume capacity or mucosal fluid transport during basal conditions. Tetrodotoxin did not abolish the gallbladder responses to intravenous cholecystokinin or vasoactive intestinal peptide, peptides known to act directly upon smooth muscle and epithelial cell receptors, respectively. It is suggested that prostaglandin E2 affects gallbladder function in vivo mainly by activation of postganglionic non cholinergic intramural nerve cells. PMID- 2906508 TI - Somatostatin inhibits prolactin secretion by multiple mechanisms involving a site of action distal to increased cyclic adenosine 3',5'-monophosphate and elevated cytosolic Ca2+ in rat lactotrophs. AB - The release of prolactin (PRL) from a clonal cell-line of anterior pituitary cells (GH4C1) was inhibited by somatostatin (SRIH) in a dose-dependent manner (ED50 nM). The inhibition (20% of control levels) was detectable within 50 s and maximal within 90 s. Thyroliberin (TRH) enhancement of PRL secretion was biphasic. SRIH inhibited both phases equally. Ionomycin in combination with the phorbol ester, TPA, mimics the TRH-elicited PRL release, and SRIH partly inhibited this effect. SRIH had no effect on TRH-stimulated formation of inositol trisphosphate, and only small effects on TRH-activated adenylate cyclase. Vasoactive intestinal peptide (VIP) and forskolin stimulated cAMP formation and PRL release potently. SRIH inhibited both effects of VIP and forskolin, and there was a close correlation between the inhibition of PRL secretion and cAMP accumulation. 8-Bromo-cAMP enhanced PRL release, an effect that was also partly reduced by SRIH. The Ca2+ channel activator, BAY-K-8644 and high extracellular K+ increased PRL release, and SRIH caused a partial reduction in the release response to both secretagogues. SRIH lowered [Ca2+]i, and markedly reduced the rise in [Ca2+]i elicited by TRH, VIP and K+. SRIH did not influence the Ca2+ spikes recorded in Na+-free solution, and had no effect on the TRH-induced membrane potential changes. Our results demonstrate that SRIH may inhibit PRL release from GH4C1 cells by (1) inhibiting hormone-sensitive adenylate cyclase, (2) blocking the effect of cAMP and (3) lowering [Ca2+]i. None of these effects is, however, sufficient to explain all the effects of SRIH, suggesting that SRIH also exerts a major action at a step subsequent to cAMP accumulation and [Ca2+]i elevation. Since the GH4C1 cells possess one single class of binding sites, this implies that the same SRIH receptor is coupled to several cellular signalling systems. PMID- 2906509 TI - Effects of some calcium antagonists on aggregation by adrenalin and serotonin and on alpha-adrenoceptor radioligand binding in human platelets. AB - The inhibitory effects of verapamil, nifedipine and diltiazem, representatives of different classes of calcium antagonists, were studied on aggregation of human platelets induced by adrenalin and serotonin (5-HT). For references, the alpha adrenoceptor-antagonists phentolamine (alpha 1 and alpha 2) and rauwolscine (alpha 2), and the 5-HT 2-receptor-antagonist ketanserin were included. Verapamil in the concentration range 10(-6) 10(-4) M inhibited both adrenalin- and serotonin-induced aggregation in a concentration-dependent manner, whereas nifedipine and diltiazem had little or no effect. Phentolamine and rauwolscine were clearly weaker than verapamil as antagonists of serotonin, and ketanserin lacked effect on adrenalin-induced aggregation. Binding studies with [3H]dihydro alpha-ergocryptine and [3H]rauwolscine on human platelet membranes showed equal numbers of binding sites, suggesting that only alpha 2-adrenoceptors were present. In the same concentration range as inhibition of aggregation was obtained, verapamil inhibited binding of either radioligand. Nifedipine, diltiazem and 5-HT were all poor inhibitors of radioligand binding. The results suggest that verapamil at high concentrations not only has alpha-adrenoceptor antagonistic properties but also exerts 5-HT-receptor blocking effects. This was not found with the other calcium channel blockers examined (nifedipine, diltiazem). PMID- 2906510 TI - The sympathetic innervation of the internal anal sphincter and rectum in the cat. AB - The distribution of the sympathetic innervation to the internal anal sphincter (IAS) and rectum and the occurrence of different types of adrenergic receptors in the two organs were investigated in anaesthetized cats. Anal pressure and rectal motility were recorded by a manometric and a volumetric method respectively. Division of both the hypogastric nerves (HGN) and the lumbar colonic nerves (LCN) reduced the anal pressure by 46 +/- 6% of the resting pressure (40.9 +/- 6.4 mmHg) and consistently increased rectal motility. Efferent electrical stimulation of the HGN as well as the LCN elicited a contraction in the anus and the rectum, which, at maximal stimulation, caused the anal pressure to reach a similar level to that recorded before division of these nerves. After injection of phentolamine the anal contraction was abolished, whereas the rectal contraction was either abolished or converted to a beta-adrenergic relaxation. Propranolol caused increased rectal contraction in response to stimulation of the HGN and the LCN, whereas the anal contraction was unaffected. The results imply that the sympathetic nerves exert a tonic excitatory effect on the IAS and a dual effect on the rectum in the cat. The results also indicate that sympathetic fibres to the IAS are conveyed in both the HGN and the LCN. Inhibitory beta-adrenergic receptors seem to be of minor importance in regulating anal pressure. PMID- 2906511 TI - Evidence that alpha 2-agonists may inhibit sympathetic transmitter secretion by an effect 'upstream' of varicosities. PMID- 2906512 TI - Somatostatin and methionine-enkephalin inhibit cholera toxin-induced jejunal net fluid secretion and release of vasoactive intestinal polypeptide in the cat in vivo. AB - A major part of the net fluid secretion that is elicited by cholera toxin in the small intestine of the cat has been shown to be mediated by intramural nervous reflex(es). The release of vasoactive intestinal polypeptide (VIP) from the small intestine is increased by cholera toxin. We report that close intra-arterial infusions of methionine-enkephalin (met-enk) and somatostatin cause a parallel reduction in cholera toxin-induced net fluid secretion and in VIP release from the small intestine of the cat. Intestinal blood flow was slightly, but significantly increased by met-enk and not influenced by somatostatin. These results strengthen the hypothesis that VIP is involved as a neurotransmitter in the nervous reflex mediating cholera toxin-induced secretion. PMID- 2906513 TI - A heterogeneous population of alpha 1-adrenoceptors mediates contraction of the isolated follicle wall from the bovine ovary. AB - Strips from Graafian follicles of bovine ovaries were tested for their contractile response in vitro in order to characterize the type of post junctional alpha-adrenoceptor involved. Electrically induced contractions were inhibited concentration-dependently by the alpha 1-antagonist, prazosin. Besides noradrenaline the alpha 1-selective agonists, methoxamine and phenylephrine, caused the strips to contract, whereas the alpha 2-selective agonists clonidine, oxymetazoline and B-HT920 were without effect. However, the alpha 1-selective antagonist prazosin gave a line with a slope less than unity in the Schild plots with noradrenaline and methoxamine. From results obtained with or without the presence of two classes of neuronal uptake blockers (desipramine and cocaine) it is concluded that the post-junctional alpha 1-receptor population is inhomogeneous. The regular appearance of the Schild plot obtained with phenylephrine may be due to involvement also of a component of noradrenaline release by this agonist. The pA2 value in the test with phenylephrine was 9.27, with a corresponding kB of 3.81 +/- 1.15 X 10(-10) M. PMID- 2906514 TI - Do alpha 2-agonists inhibit sympathetic transmitter secretion in part by depressing a Ca2+ component of the nerve impulse 'upstream' of varicosities? PMID- 2906515 TI - The effect of beta 2-adrenoceptor activation on ion-shifts and fatigue in mouse soleus muscles stimulated in vitro. AB - The resting membrane potential (RMP), the intracellular free Na+ concentration ([Na+]i) and the intracellular free K+ concentration ([K+]i), were measured with double-barrelled ion-selective microelectrodes in mouse soleus muscles in vitro. In addition, the Na+ contents and K+ contents have been measured with the flame photometric technique. At rest the beta 2-selective adrenoceptor agonist terbutaline (10(-5) M) increased the membrane potential and [K+]i, and decreased [Na+]i when compared with control muscles. During a 5 min stimulation period the muscles, which were incubated with the beta 2-adrenoceptor agonist, showed a smaller depolarization, a smaller decrease in [K+]i and a smaller increase in [Na+]i than stimulated control muscles. This difference was probably associated with an increased rate of Na-K-pumping in the beta 2-adrenoceptor stimulated muscles. The beta 2-agonist treated muscles were more resistant to fatigue than control muscles. This effect was significant with 10(-6) M terbutaline (25 degrees C). A depolarization obtained by increasing [K+]o was shown to reduce the maximal tension. It is postulated, that the K+ shifts, which are responsible for the depolarization during muscle activity, are one of the mechanisms underlying muscle fatigue. PMID- 2906516 TI - Do concentrations of neurotransmitters in lumbar CSF reflect cerebral dysfunction in depression? AB - Concentrations of the amines and amine metabolites dopamine (DA), noradrenaline (NA), adrenaline (A), serotonin (5-HT), homovanillic acid (HVA), 3-methoxy-4 hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA) and of the peptides, vasopressin (AVP), vasoactive intestinal polypeptide (VIP), thyrotropin releasing hormone (TRH) and cholecystokinin (CCK) were measured in lumbar cerebrospinal fluid (CSF) in patients with depression and compared with that of controls. Diagnostic classifications were performed according to ICD-9 and the Newcastle Rating Scales for Depression. The severity of depression was measured by Bech-Rafaelsen melancholia scale. Significantly decreased concentrations of CSF-A and AVP were found in as well endogenous as in non-endogenous depression, whereas reduced levels of CSF-VIP were found only in the non-endogenous group. CSF-5-HT and DA were significantly increased in endogenously depressed patients. In these studies patients with non-endogenous depression were not included. No relationship between severity of depression and concentrations of neurotransmitters was found. For most of the neurotransmitters no correlation between concentrations measured at the lumbar and at the ventricular level seems to exist. This finding indicates that measurements on CSF collected from the lumbar sack not necessarily are indicative for concentrations measured at more central levels. Although several transmitter systems most likely are disturbed in depression, results from studies on lumbar CSF should be interpreted with precaution, until further information about origin and distribution of neurotransmitters in CSF has been obtained. PMID- 2906517 TI - N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ): a new tool to probe CNS receptor function. PMID- 2906518 TI - Regulation of rat hypothalamic corticotropin-releasing hormone secretion in vitro: potential clinical implications. AB - In summary, 5HT, ACh, NE, E and DA appear to stimulate hypothalamic CRH secretion whereas activation of the GABA/BZD system seems to decrease the responsivity of the CRH neuron to stimulatory neurotransmitters (Fig. 6). Hypothalamic CRH released from the hypothalamic neuron not only activates the HPA axis, but also stimulates the locus coeruleus-norepinephrine system (LC) and the central sympathetic system (CSS). CRH also induces secretion of hypothalamic POMC gene derived peptides, such as ACTH, beta-EP, alpha-MSH and CLIP. These peptides as well as CRH itself, decrease the responsivity of the CRH neuron to stimulatory inputs. In addition, glucocorticoids restrain the activity of both the CRH neuron and the locus coeruleus and may also inhibit the secretion of POMC gene-derived peptides by the POMC neurons of the arcuate nucleus. Hypothalamic CRH secretion is regulated also by a number of mediators of the immune response, such as IL-1, IL-2, TNF-alpha and PGF2 alpha, PAF and EGF. Although the physiologic significance of this regulation is largely unknown, it is tempting to speculate that cytokines and mediators of inflammation released in vivo may activate the HPA axis to trigger a glucocorticoid-mediated counter-regulatory mechanism to restrain the immune system (Fig. 7). (Formula: see text). Fig. 7. Schematic representation of the interactions between the HPA axis and the immune system. Continuous lines represent stimulatory inputs and interrupted lines represent inhibitory inputs. In conclusion, our in vitro hypothalamic organ culture system allowed us to examine the regulation of CRH secretion in a direct and specific manner. Some of our observations may help with better understanding of the role played by CRH in the complex symptomatology of stress. In making extrapolations and interpretations from the in vitro data, however, we should try to keep in mind the words of Claude Bernard, "... If we break up a living organism by isolating its different parts it is only for the sake of ease in analysis and by no means in order to consider them separately. Indeed when we wish to ascribe to a physiological quality its value and true significance we must always refer it to this whole and draw our final conclusions only in relation to the effects in the whole". PMID- 2906519 TI - Is the benzodiazepine/GABA receptor chloride ionophore complex involved in physical and emotional stress? PMID- 2906520 TI - Neurochemical and electrophysiological events underlying stress-induced depression in an animal model. AB - This paper has described an animal (rodent) model of depression in which depression-like characteristics are produced by exposure of animals to stressful events that they cannot control. This model, called "stress-induced depression," appears to be mediated by stress-induced changes in brain norepinephrine (NE), and evidence now indicates that a large depletion of NE in the Locus Coeruleus region of the brain stem (LC) is critical for producing the behavioral disturbance seen in this model. To explain the functional significance of NE depletion in the LC, it has been suggested that this change results in decreased stimulation, (i.e., functional blockade) of alpha-2 receptors that normally inhibit firing of LC neurons. Consequently, LC neurons should be disinhibited in stress-induced depression. The final part of this paper describes findings from electrophysiological measurement of LC activity. Prior to measuring changes occurring in stress-induced depression, studies examined the basic role played by alpha-2 receptors in LC activity. These receptors were found to regulate the responsivity of LC neurons to excitatory stimuli, so that pharmacological blockade of these receptors increased the firing of LC neurons to excitatory input. When LC activity was then measured in stressed animals showing behavioral depression, responsivity of LC neurons to excitatory input was elevated in comparison to animals not exposed to stress. Also, administration of an alpha-2 blocking drug could not increase responsivity of LC neurons in stressed animals, which further indicated that alpha-2 receptors in the LC region were functionally blocked in these animals. Finally, the amount that LC neurons increased their firing to an excitatory stimulus (i.e., an index of alpha-2 receptor blockade) was highly correlated with the amount of behavioral depression seen in an activity test conducted just prior to electrophysiological measurement. These electrophysiological findings indicate that LC neurons are disinhibited in stress induced depression, and that this disinhibition is particularly characterized by increased responsivity of LC neurons to excitatory input, which is indicative of alpha-2 receptor blockade. These findings further support the view that the LC is involved in stress-induced depression, and are consistent with a proposed mechanism that attributes behavioral disturbance in the model to disinhibition of LC neurons arising from subnormal activation of inhibitory alpha-2 receptors. PMID- 2906521 TI - Implications of behavioral sensitization and kindling for stress-induced behavioral change. PMID- 2906522 TI - Hypophysiotropic regulation of stress-induced ACTH secretion. PMID- 2906524 TI - More on converting i.v. histamine H2 therapy to oral therapy. PMID- 2906523 TI - CD4+, CD8+ cells, IgE and prick test in infants allergic to cow's milk. AB - Three groups of infants were formed according to the type of feeding: I-breast milk from mothers without any kind of elimination diet, II-cow's milk-based formula, and III-breast milk till 2 months of age and after that, cow's milk formula. CD4 and CD8 were determined by monoclonal antibodies technique, IgE by ELISA and prick test with either intact or enzymatically digested cow's milk antigens. The average age of onset of the atopic disease in the first group was 2m 10d +/- 15d, in the second: 3m 4d +/- 14d, and in the third: 2m 11d +/- 1m 18d. The number of CD4 in group II was the lowest while in group III was the highest. CD8 value in the second group was higher than in the others. Ratio between CD4 and CD8 in cow's milk-fed infants was the lowest. Total serum IgE level in group II was the lowest although the mean values of the three groups were significantly increased. Prick tests, with at least one antigen, were positive in 75%, 50% and 48% in group I, II and III respectively. It is suggested that the behaviour of the parameters studied would be related to the dose of cow's milk proteins received through breast milk in breast-fed infants; to the relatively great amount of cow's milk antigens and to the lack of breast-feeding in infants fed on cow's milk formula; and to the interaction of such factors in infants fed with both cow's milk and breast milk. PMID- 2906525 TI - Identification of carriers of Duchenne muscular dystrophy: value of molecular analysis. AB - Currently, molecular methods are the most accurate diagnostic tools for carrier detection and prenatal diagnosis of Duchenne muscular dystrophy (DMD). This report illustrates the value of molecular diagnosis as opposed to previous diagnostic methods, the need for frequent re-evaluations as new methodologies develop, and the necessity for in-depth genetic counseling. In Family 1, the proposita was predicted to be a carrier by an indirect assay (abnormal in vitro muscle ribosomal protein synthesis). DNA analysis using restriction fragment length polymorphisms (RFLPs) indicated that she was not a carrier. She gave birth to a predicted non-affected male, who inherited the gene in question. In Family 2 the proposita, an obligate carrier, was initially evaluated by RFLP analysis. Two pregnancies were monitored by first trimester chorionic villous sampling. Re evaluation indicated that all affected individuals, including one of the embryos, carried a deletion of the dystrophin gene. The identification of an RFLP within the region containing the deletion allowed unambiguous determination of the carrier status of all individuals. PMID- 2906526 TI - Presence and distribution of vimentin in cynomolgus monkey trabecular cells. AB - The role of the trabecular meshwork in the ocular outflow tract has made it the object of considerable study. Recent work has examined the presence and function of microfilaments and microtubules in the cytoskeleton of cultured cynomolgus monkey trabecular cells. In this study, we used an indirect immunofluorescence technique to investigate the presence and distribution of the intermediate filament vimentin in cultured cynomolgus monkey trabecular cells. The cytoskeletal active agents cytochalasin B, colchicine, nocodozole, and taxol were also employed to investigate the role of vimentin in these cells. Vimentin formed a network of filaments that radiated throughout the cytoplasm from the nucleus to the cellular projections and cell membrane. The extensiveness of the vimentin network, and the cell shape, were observed to vary according to the degree of cell confluence, the degree of cell spread, and the degree of cell/cell contact. Cells in the less-confluent periphery had extensive vimentin networks and greater cell spreading and were polygonal in shape. Cells in the more confluent areas had a less-extensive vimentin network, underwent less cell spreading, and were primarily fusiform in shape. The change in cellular morphology induced by colchicine, nocodozole and taxol was proportional to the extensiveness and the degree of change of the vimentin network. Our observations have identified a proportional association between the extensiveness of the vimentin network, changes in the vimentin organization, and alterations in cellular morphology that is suggestive of a role for vimentin in determining cellular structure and shape.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2906527 TI - The increase in number of orchidopexies: rather cause than prevention of male infertility. AB - Because of the present tendency to operate early on undescended testes, the indication for orchidopexy amounts to six-to-seven times the justified number in the Netherlands and two-to-three times in Flanders! The tendency to operate early has surely caused more fertility damage than prevented it. This critical statement asks for consideration and urges everybody concerned to a more accurate and repeated physical examination of the genital region and to a conservative attitude regarding treatment. PMID- 2906528 TI - Liver functions in hepatocytes entrapped within calcium alginate. PMID- 2906529 TI - The neuroexcitotoxic amino acids glutamate and aspartate are altered in the spinal cord and brain in amyotrophic lateral sclerosis. AB - Because recent studies showed a systemic defect in glutamate metabolism in amyotrophic lateral sclerosis (ALS), we measured the levels of free amino acids in frontal and cerebellar cortex and two areas of spinal cord obtained at autopsy from 22 patients who died of this disease. Glutamate levels were significantly decreased (by 21 to 40% of control values) in all areas investigated; cervical and lumbar spinal cord showed the greatest change. Aspartate levels were also significantly reduced (by 32 to 35%) in the spinal cord only. A positive correlation was shown between the changes of glutamate and aspartate as well as a significant alteration in the glutamate to glutamine ratio in the spinal cord of patients with ALS. Although we cannot exclude the possibility that these abnormalities may partly result from neuronal cell loss, the data suggest the presence of a generalized defect that may affect the neurotransmitter and metabolic pool of glutamate. The defect may be expressed more severely in the spinal cord than in other central nervous system areas. These results, taken together with the previously shown systemic abnormality, raise the possibility that distribution of glutamate between the intracellular and extracellular pool may be altered in ALS and may mediate the neurodegeneration. PMID- 2906530 TI - Brain neurotransmitters in glycine encephalopathy. AB - We measured neurotransmitter markers in autopsied brain of infants with glycine encephalopathy (GE). Because patients with GE develop intractable seizures, special attention was devoted to those neurotransmitter systems implicated in human epilepsy. Mean levels of glycine in the frontal cortex of GE patients were three times higher than control values. No abnormalities were observed for concentrations of gamma-aminobutyric acid (and related receptors), other major neurotransmitter amino compounds, or activities of cholineacetyltransferase and aspartate aminotransferase. Mean acetylcholinesterase activity was significantly elevated by 46%. As experimental data suggest, glycine markedly potentiates the action of the excitatory neurotransmitter glutamic acid. To the extent that the brain seizures in patients with GE can be explained by this mechanism, pharmacotherapy with excitatory amino acid antagonists may represent a new approach to the treatment of GE. PMID- 2906531 TI - Subclinical effects of groundwater contaminants. II. Alteration of regional brain monoamine neurotransmitters by benzene in CD-1 mice. PMID- 2906532 TI - [Cryptorchidism, orchidopexy and testicular cancer: report of a case showing this association]. PMID- 2906533 TI - [Intracellular location of vacuoles with acid phosphatase activity in trophozoites of Entamoeba histolytica adhered to guinea pig cecal epithelium]. PMID- 2906534 TI - [Azelastine inhibits bronchoconstriction induced by histamine and leukotriene C4]. PMID- 2906535 TI - [Lower epigastric artery as a free graft. A new alternative in direct myocardial revascularization]. PMID- 2906536 TI - The use of bronchodilators in the young infant. PMID- 2906538 TI - Behavior completion versus stimulus control in compulsive gambling. Implications for behavioral assessment. PMID- 2906537 TI - Scopolamine interactions with D1 and D2 antagonists on radial-arm maze performance in rats. AB - Recent evidence indicates that acetylcholine and dopamine play complementary roles in cognitive as well as motor functions. In our previous study, the dopamine receptor blocker, haloperidol, was found to attenuate the radial-arm maze choice accuracy deficit caused by the muscarinic acetylcholine receptor blocker, scopolamine. Haloperidol has activity in blocking both D1 and D2 dopamine receptor subtypes. The current study was conducted to determine whether this dopamine-acetylcholine interaction specifically involved D1 or D2 dopamine receptors. The D1 antagonist, SCH 23390, and the D2 antagonist, raclopride, were administered with a dose of scopolamine which caused choice accuracy deficits in the radial-arm maze. The scopolamine-induced deficit was reversed by SCH 23390, the D1 antagonist, indicating that D1 blockade alone is sufficient to reverse the amnestic effects of muscarinic blockade. There was no indication in this study that the D2 blocker, raclopride, had a similar effect. However, this does not mean that such an effect may not be present at other doses of raclopride or with other D2 antagonists. The present finding that D1 blockade counteracts scopolamine-induced cognitive dysfunction not only furthers the understanding of dopamine-acetylcholine relationships in cognitive function, it also suggests a promising direction for the development of treatments for cognitive dysfunction due to cholinergic loss. PMID- 2906539 TI - DNA polymorphisms defined by the Tu108 probe map to the Tla region of mouse chromosome 17. PMID- 2906540 TI - The leghaemoglobins. PMID- 2906541 TI - Disturbances in regulation of catecholamine neuromediation in alcoholism. AB - Dopamine content of blood, activity of adenylate- and guanylate cyclases in platelets and lymphocytes, catechol-O-methyltransferase in erythrocytes, dopamine beta-hydroxylase in blood plasma, monoamine oxidase in platelets, cAMP and cGMP content of blood, and the intensity of 3H-DA uptake by platelets have been investigated in alcoholic patients at different clinical states. Most of these indices have been studied in the brain and blood of rats displaying different affinities to alcohol. The results indicate that, in addition to the previously described disturbances of DA turnover, changes occur in the functions of enzyme and receptor systems involved in the mechanism of catecholamine neuromediation. Rats preferring and avoiding alcohol exhibit different DA and cyclic nucleotide concentrations in the blood and a trend towards different activity of some enzymes in the brain. It is suggested that: (1) the disturbances in the regulation of catecholamine neuromediation are involved in the mechanism of development of alcohol dependence; (2) the genetically-determined abnormalities of catecholamine neuromediation may contribute to an individual's attitude to alcohol. PMID- 2906542 TI - Increased rate of ethanol elimination and elevated blood acetate in asthmatics on corticosteroid, beta-2-sympathicomimetic and theophylline treatment. AB - The rate of ethanol elimination and blood acetate concentrations after a peroral dose of alcohol were measured in eight asthmatic patients receiving high-dose corticosteroid, sustained release theophylline and beta-2-sympathicomimetic treatment and in eight nonalcoholic, healthy controls. Mean ethanol elimination rate (ER) and mean blood acetate concentration (AC) were significantly (P less than 0.01) higher in asthmatics (ER = 134.8 +/- 12.9 mg/kg/hr, AC = 1.13 +/- 0.25 mM) than in controls (ER = 100.2 +/- 12.3 mg/kg/hr, AC = 0.64 +/- 0.10 mM). In the asthmatics there was a significant negative correlation between the age and the rate of ethanol elimination (r = -0.890, P less than 0.01); in the control group, however, this correlation was of lower degree (r = -0.423) and did not achieve statistical significance. Enhanced ethanol metabolism in asthmatics is possibly due to the effect of drugs. Our results suggest that ethanol elimination rate is increased in asthmatics receiving medication and that the effect is most significant in younger age groups. PMID- 2906543 TI - A rapidly acquired one-way conditioned avoidance procedure in rats as a primary screening test for antipsychotics: influence of shock intensity on avoidance performance. AB - Antipsychotics selectively disrupt relatively weak responses maintained by conditioned stimuli compared with stronger responses maintained by unconditioned stimuli. The present study describes an easily taught and rapidly acquired (within one 15-trial session) one-way conditioned avoidance procedure for rats suitable for screening of drugs for potential antipsychotic activity. This was achieved by using an easily acquired response (running, part of the species specific defense reaction repertoire), a clearly discriminated conditioned stimulus and determination of the appropriate strength of the unconditioned stimulus (i.e. shock level) for this procedure. Behavior acquired under these described conditions resulted in stable performance over long retest periods. By using either a low or high intensity of shock level under which the animals were trained and tested, the difference between the dose of haloperidol and chlorpromazine able to disrupt avoidance and that which disrupted escape response rates was increased. This effect was also observed for morphine, which inhibited both avoidance and escape responses at similar dose levels only under low shock conditions. At a high shock condition morphine more selectively inhibited avoidance responding. Diazepam did not affect avoidance behavior under the conditions described here. PMID- 2906544 TI - Human trials of experimental AIDS vaccines: recombinant envelope proteins. PMID- 2906545 TI - Quantitative analyses of voluntary orofacial motor control in schizophrenia and tardive dyskinesia. AB - This paper reports the results of an investigation of voluntary control of lip, jaw, and tongue movements in schizophrenic patients with and without tardive dyskinesia. The aims of the study were to determine if voluntary orofacial motor control is disrupted in schizophrenia and to evaluate the relationship between voluntary motor control deficits and selected neurological and behavioral variables. Twenty-two schizophrenic patients and 13 normal control subjects were studied. Of the patients, 11 had moderate to severe TD. Analyses were made of performance on pursuit tracking tasks to evaluate differences between TD and non TD patients and between medicated and currently unmedicated patients. The results indicated significant group differences in voluntary orofacial motor control. The finding that many non-TD patients exhibited voluntary motor dyscontrol suggests that this may represent a disorder independent of the involuntary dyskinesia. The findings indicated that the level of neuroleptic and/or antiparkinsonian medication was unrelated to the degree of voluntary motor control impairment. The results are discussed in terms of probable neurophysiological mechanisms underlying the motor control deficits in schizophrenia. PMID- 2906546 TI - Neuroleptics and their metabolites binding to alpha 1 and D2 receptors. PMID- 2906547 TI - Propranolol in the treatment of neuroleptic-induced akathisia (NIA) in schizophrenics: a double-blind, placebo-controlled study. PMID- 2906548 TI - A simple method for the purification of dipeptidyl aminopeptidase IV from porcine kidney using HPLC. AB - Dipeptidyl aminopeptidase IV (E.C. 3.4.14.5) has been purified to homogeneity using "soft-column" chromatography on Sephadex G-200, DEAE-cellulose, gly-pro-AH Sepharose and finally HPLC on TSK G-3000SW. The purification by HPLC is fast and gives a better yield of pure enzyme than procedures which have been described previously. The enzyme obtained in this manner has a high specific activity (86 U/mg using a saturating level of gly-pro-4-nitroanilide as substrate) and was free of contaminating peptidase activities. Our preparation of DAP IV is suitable for peptide sequencing studies by fast atom bombardment mass spectrometry. PMID- 2906549 TI - Hyperprolactinaemia. PMID- 2906550 TI - Isolated cytoskeletons of human blood platelets: dark-field imaging of coiled and uncoiled microtubules. AB - Detergent extraction of human blood platelets pre-treated with Taxol to stabilize microtubules allows isolation of marginal band (MB) cytoskeletons. We studied MB cytoskeleton structure using dark-field light microscopy and negative stain electron microscopy (EM). Dark-field illumination clearly demonstrated the "hoop" shape of MB cytoskeletons in unfixed suspensions where the microtubule coils had a mean diameter of 2.87 microns (+/- 0.18 micron, SD). Microtubules were uncoiled by brief exposure to trypsin (2 ng/micrograms protein) or by NaCl (154-600 mM) but not by DNase I, which removed approximately 40% of total actin, but had no effect on dark-field images of microtubule coils. As microtubules uncoiled, a single fiber emerged from the hoop and gradually lengthened as the brightness of the hoop diminished; these fibers correspond to the single microtubules seen by EM. Polypeptides of coiled and uncoiled MB cytoskeletons were analyzed by SDS PAGE. When microtubules became uncoiled, no changes in the major components (alpha- and beta-tubulin, IEF-51K, or actin) were found. However, a number (greater than 10) of minor polypeptides, each less than 5% of total cytoskeletal protein and with an Mr ranging from 80,000- greater than 260,000, were decreased in "uncoiled" MB cytoskeletons. These results implicate one or more of these minor polypeptides in maintenance of hoop integrity. Dark-field light microscopy thus provides an approach toward investigating the mechanism(s) involved in maintaining the microtubule coil of the platelet marginal band. PMID- 2906551 TI - Effect of microtubule reactive drugs on steroid- and centrifugation-induced germinal vesicle migration during goldfish oocyte meiosis. AB - During the process of progestogen-induced meiotic maturation in the goldfish oocyte, the oocyte nucleus (germinal vesicle, GV) migrates to the sperm entry site or micropyle at the animal pole. Following GV migration (GVM) to the micropyle, the nuclear membrane undergoes dissolution (GVD) and the cell enters metaphase I in preparation to generate the first polar body. Microtubule destabilizing drugs including colcemid, nocodazole and vinblastine were found to elicit GVM, mimicking the process which occurs just prior to the prophase I metaphase I transition during steroid induced oocyte meiotic maturation. In addition, these drugs enhanced the induction of GVM by 17 alpha, 20 beta dihydroxy-4-pregnen-3-one, a potent, naturally occurring meiotogenic steroid in this species. By contrast, taxol, a microtubule stabilizing drug, was found to inhibit steroid induced GVM. A new assay for centrifugation induced GVM was applied to the goldfish oocyte in order to assess effects of steroids and drugs on GVM, without the complication of GVD or the restrictions imposed by the slow time course of naturally occurring GVM. The effective centrifugal force (ECF) required to elicit GVM in 50% of the oocytes (ECF50) decreased significantly after short incubations (1-5 hr) of oocytes with either 17 alpha,20 beta dihydroxy-4-pregnen-3-one or microtubule disrupting drugs (i.e., colcemid, nocodazole, or vinblastine). A working hypothesis, modeled after the effects of microtubule disrupting agents on intermediate filament arrays in somatic cells, is proposed in which a small number of microtubules or other polymeric tubulin units are responsible for maintaining a cytoskeletal array.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2906552 TI - Post-translational modifications of tubulin and the dynamics of microtubules in mouse oocytes and zygotes. AB - The distribution of post-translationally modified forms of tubulin has been studied in mouse oocytes arrested in meiotic metaphase II and in interphase eggs after fertilisation. Tyrosinated and acetylated microtubules are present in the meiotic spindle but detyrosinated ones are not. Acetylation only occurs in the most stable subpopulation of microtubules in the spindles ("pole to kinetochore"). After fertilisation, many microtubules of the interphase array become acetylated, but detyrosination occurs only at a very low level. PMID- 2906553 TI - Catecholamines and plasma potassium. AB - There are many circumstances in which disease or its treatment may influence potassium homeostasis, and yet serious consequences resulting from potassium changes are uncommon. This article explores the mechanisms involved in short-term potassium control and describes their clinical implications. PMID- 2906554 TI - Effects of naloxone and opioid agonists on gastric excitatory responses to stimulation of the vagus nerve in cats. AB - 1. An investigation was made into the contribution of endogenous opioids to the initial and delayed excitatory response of the stomach induced by stimulation of the vagal trunk in cats. 2. Naloxone (100 to 1000 micrograms kg-1) had no effect on the initial excitatory response to stimulation of the vagal efferent fibres. However, the same treatment dose-dependently enhanced the delayed excitatory response to stimulation of the vagal afferent fibres. 3. In comparison with the mu-opioid-receptor agonist, [D-Ala2, MePhe4, Gly-ol5]enkephalin and the kappa opioid-receptor agonist dynorphin A (1-13), lower doses of methionine enkephalin [( Met]enkephalin) markedly inhibited the excitation caused by stimulation of the vagal efferent and afferent fibres. The inhibitory effect of [Met]enkephalin was antagonized by naloxone. 4. The delta-opioid-receptor selective agonist [D-Pen2, D-Pen5]enkephalin mimicked the inhibitory effects of [Met]enkephalin and inhibition by [D-Pen2, D-Pen5]enkephalin was antagonized by the delta-opioid receptor antagonist, ICI 174,864. 5. It is concluded that the inhibitory effects of exogenous opioids on the excitatory response of the stomach to stimulation of the vagal efferent and afferent fibres are mediated, at least in part, by delta opioid-receptors. Naturally occurring opioids may participate in the inhibition of the delayed gastric excitation to stimulation of the vagal afferent fibres. PMID- 2906555 TI - Behavioural responses to the selective D1-dopamine receptor agonist R-SK&F 38393 and the selective D2-agonist RU 24213 in young compared with aged rats. AB - 1. In aged male Sprague-Dawley rats (22 months) with a selective loss of D2- but not of D1-dopamine receptors, stereotyped behaviour induced by 0.5 mg kg-1 apomorphine was increased and prolonged in comparison with young (4 month) counterparts. This suggested a pharmacokinetic effect rather than a pharmacodynamic change. 2. The syndrome of non-stereotyped behavioural responses to the selective D1-agonist R-SK&F 38393, 1.25-20.0 mg kg-1, was unchanged in aged vs young animals, but the topography of individual behaviours constituting this overall syndrome was altered with aging. 3. Neither the overall syndrome of low intensity stereotyped behaviour nor the topography of individual behaviours induced by the selective D2-agonist RU 24213, 1.25-20.0 mg kg-1, were altered in aged vs young animals. 4. Loss of D2- but not D1-receptors with aging was therefore found to be associated with no change in responsivity to a D2-receptor agonist. The decreased intense grooming and increased vacuous chewing responses to the D1-agonist with aging parallel the previously demonstrated effects of selective D2-antagonists on these D1-stimulated behaviours. 5. It is suggested that age-related decline in D2-receptor activity may have greater functional consequences in relation to D1-:D2-interactions than in simply influencing responsivity to a D2-agonist. Such interactive effects should be taken into account when considering the pathophysiology and treatment of age-related extrapyramidal movement disorders. PMID- 2906556 TI - Modulation of the actions of tyrosine by alpha 2-adrenoceptor blockade. AB - 1. Eight normal subjects were given, in double-blind, random order L-tyrosine 50, 250 and 500 mg kg-1 and placebo orally. Plasma tyrosine concentrations rose in a dose-dependent manner, without affecting the concentrations of the other large neutral amino acids. Tyrosine stimulated the secretion of prolactin and thyrotrophin (TSH) but had no effect on the plasma concentrations of adrenocorticotrophic hormone (ACTH), cortisol, growth hormone or the gonadotrophins. 2. The lack of a stimulant effect of tyrosine on ACTH secretion was presumed to be due to activation of one of the negative feedback mechanisms that control the rate of synthesis and release of the catecholamines, and this hypothesis was tested by examining the effects of the alpha 2-adrenoceptor antagonist idazoxan on the actions of tyrosine. 3. Seven normal males were given on 6 separate occasions tyrosine 250 and 500 mg kg-1 and placebo orally following pretreatment with saline and idazoxan (0.1 mg kg-1 i.v.). Following pretreatment with idazoxan, tyrosine stimulated the secretion of ACTH and noradrenaline in a dose-dependent manner, although neither tyrosine nor idazoxan on their own had any effect on the secretion of either substance. 4. The lack of effect of tyrosine when given on its own appears to be due, to partly, to activation of alpha 2-adrenoceptors, which inhibit the release of noradrenaline. Idazoxan caused a small increase in systolic blood pressure, both when given on its own and in combination with tyrosine. Neither tyrosine nor idazoxan had any significant effect on the state of behavioural arousal, as measured by visual analogue scales, or on the secretion of growth hormone or the gonadotrophins. PMID- 2906557 TI - Pharmacological analysis of postjunctional alpha-adrenoceptors mediating contractions to (-)-noradrenaline in the rabbit isolated lateral saphenous vein can be explained by interacting responses to simultaneous activation of alpha 1- and alpha 2-adrenoceptors. AB - 1. The pharmacological characteristics of the alpha-adrenoceptor population in the rabbit isolated saphenous vein has been examined with (-)-noradrenaline (NA), as principal agonist, and a number of antagonists with selectivity for either alpha 1- or alpha 2-adrenoceptors. 2. The rank order of potency of various agonists is consistent with a population of alpha 2-adrenoceptors; UK-14304 greater than (-)-noradrenaline = (-)-adrenaline greater than B-HT 920 = cirazoline greater than phenylephrine greater than amidephrine, but the rank order of pA2 values for the antagonists against (-)-noradrenaline: BDF-6143 greater than rauwolscine = prazosin greater than CH-38083 = YM-12617 greater than Wy-26703 = phentolamine greater than corynanthine, is indicative of a mixed population of alpha 1- and alpha 2-adrenoceptors or, alternatively, a new subtype with characteristics of both the alpha 1- and alpha 2-subtypes. 3. Further evidence for two discrete populations of alpha-adrenoceptors is provided by, (a) the potent but non-competitive effect of prazosin against (-)-noradrenaline, (b) the presence of a component of the contractions elicited by NA and phenylephrine which is resistant to the selective alpha 2-adrenoceptor antagonists rauwolscine and CH-38083: these responses were inhibited by the selective alpha 1 adrenoceptor antagonists prazosin and YM-12617, but not by the selective alpha 2 adrenoceptor antagonist BDF-6143 and, (c) the relative potency of the yohimbine diastereoisomers rauwolscine and corynanthine against NA, phenylephrine and UK 14304. 4. In spite of the overwhelming evidence for a population of postjunctional alpha 2-adrenoceptors, prazosin was similarly effective against all agonists and failed to discriminate between those with putative selectivity for alpha 1- and alpha 2-adrenoceptors. This suggests an interaction of the effects of agonists at the two alpha-adrenoceptor subtypes. 5. An attempt has been made to reconcile a number of paradoxical observations with regard to the identification of postjunctional alpha 2-adrenoceptors in vitro, and it is suggested that in many of the isolated blood vessels presently available for examination both subtypes reside on the same smooth muscle cell. The pharmacological consequences of multiple subtypes of receptors mediating the same response is considered. PMID- 2906558 TI - An attempt at selective protection from phenoxybenzamine of postjunctional alpha adrenoceptor subtypes mediating contractions to noradrenaline in the rabbit isolated saphenous vein. AB - 1. An attempt has been made, with the irreversible alpha-adrenoceptor antagonist phenoxybenzamine, to find the conditions under which postjunctional alpha 1 adrenoceptors in the rabbit isolated saphenous vein can be inactivated, such that postjunctional alpha 2-adrenoceptors can be studied in isolation. 2. Following exposure to various concentrations of phenoxybenzamine, no evidence was found for a selective inactivation of the postjunctional population of alpha 1 adrenoceptors: the "rauwolscine-resistant' (alpha 1-) and the "rauwolscine sensitive' (alpha 2-) responses to (--)-noradrenaline were similarly affected. 3. However, in "receptor protection' experiments following exposure to a combination of phenoxybenzamine and the selective alpha 2-adrenoceptor antagonist rauwolscine, the remaining response to (--)-noradrenaline appeared to be mediated by a single population of postjunctional alpha 2-adrenoceptors: the response was insensitive to prazosin and rauwolscine was more potent than corynanthine. 4. Partial isolation of the alpha 1-adrenoceptor population was attempted by pre exposure of the preparation to a combination of phenoxybenzamine and a selective alpha 1-adrenoceptor antagonist, i.e. prazosin or YM-12617. Following receptor protection, the inhibition produced by "selective' concentrations of either of these alpha 1-adrenoceptor antagonists were not significantly different from that observed in control preparations (no phenoxybenzamine). However, the selective alpha 2-adrenoceptor antagonists rauwolscine and CH-38083 were still able to inhibit part of the remaining responses to NA. This is interpreted as indicating that, in addition to protecting the putative postjunctional alpha 1 adrenoceptors, these procedures fail to produce complete inactivation of postjunctional alpha 2-adrenoceptors. 5. It is concluded that, although phenoxybenzamine appeared to be non-selective for the two populations of postjunctional alpha-adrenoceptors in the rabbit isolated saphenous vein, inclusion of a "selective' concentration of a competitive antagonist during the inactivation period results in differing degrees of functional protection of each subtype. Pharmacological isolation was possible for alpha 2-adrenoceptors but not convincingly for alpha 1-adrenoceptors. PMID- 2906559 TI - H1- and H2-receptor characterization in the tracheal circulation of sheep. AB - 1. The effects of histamine, the specific H1-agonist SKF 71481-A2 and the H2 agonist dimaprit were examined on tracheal vascular resistance in sheep anaesthetized with pentobarbitone. Tracheal vascular resistance was determined by perfusing the cranial tracheal arteries at constant flows and measuring inflow pressures. Changes in tracheal smooth muscle tone were also measured. 2. Histamine and SKF 71481-A2 contracted the tracheal smooth muscle and this effect was blocked by the H1-antagonist mepyramine. Stimulation of H2-receptors with dimaprit had no effect on tracheal smooth muscle tone. 3. Histamine had a complex action on the tracheal vasculature producing either a triphasic change (early dilatation then constriction followed by late dilatation) or just a constriction. SKF 71481-A2 always produced a biphasic change in vascular resistance (dilatation followed by constriction). Dimaprit dilated the tracheal vasculature. 4. The late dilatation produced by histamine in some sheep was blocked by bilateral cervical vagotomy but the mechanism for this effect is not known. No other responses to histamine, SKF 71481-A2 or dimaprit were affected by vagotomy. 5. The vasoconstriction produced by histamine and SKF 71481-A2 was antagonized by mepyramine indicating a H1-receptor-mediated effect. Cimetidine had no effect on the vasoconstriction to histamine suggesting a lack of involvement of H2 receptors. 6. The vasodilatation produced by histamine and SKF 71481-A2 was also antagonized by mepyramine, again suggesting a H1-receptor-mediated action. Cimetidine had no effect on the vasodilator response to histamine indicating no involvement of H2-receptors in this response. 7. The dilator effect of dimaprit was antagonized by cimetidine suggesting this effect was mediated by H2 receptors. 8. We conclude that H1-receptors in the various parts of the sheep tracheal vasculature can cause increases and decreases in total tracheal vascular resistance; that H2-receptors decrease resistance; and that the tracheal smooth muscle contracts on activation of H1-receptors but has no response to H2 agonists. PMID- 2906560 TI - Quinoxalinediones selectively block quisqualate and kainate receptors and synaptic events in rat neocortex and hippocampus and frog spinal cord in vitro. AB - 1. Two quinozalinediones, FG9041 and FG9065, which had previously been shown to displace binding to the quisqualate receptor, were tested on rat neocortex and frog spinal cord in vitro against depolarizations induced by quisqualate, kainate and N-methyl-D-aspartate (NMDA). In both preparations effects of quisqualate were reduced the most and those of NMDA the least. 2. The near unitary slopes of the Schild plots were consistent with a competitive type of interaction. pA2 values for FG9041 were estimated to be 6.6, 6.1 and 5.1 in frog cord and 5.9, 5.3 and and about 4 in the rat neocortex for quisqualate, kainate and NMDA antagonism, respectively. FG9065 gave equivalent pA2 values of 6.2, 5.6 and 4.5. 3. At concentrations, which were without effect on depolarizations induced by NMDA, FG9041 and FG9065 reduced or blocked synaptically-evoked field potentials in hippocampal and neocortical slices superfused with normal magnesium-containing medium. Since these synaptic components are also insensitive to NMDA antagonists, these results are consistent with their mediation by postsynaptic receptors of the quisqualate (or kainate) type. 4. By contrast, quinoxalinediones had only limited effects on spontaneous epileptiform activity seen in both neocortical and hippocampal preparations when superfused with magnesium-free medium. These burst discharges were, however, abolished by NMDA antagonists. 5. In the frog spinal cord the early component of the dorsal root to ventral root reflexes was selectively reduced by FG9041 whereas NMDA antagonists reduced the longer latency components. 6. Our results suggest that the quinoxalinediones are likely to be useful pharmacological probes for elucidating the role of non-NMDA receptors in the vertebrate central nervous system. PMID- 2906561 TI - Quipazine reduces food intake in the rat by activation of 5-HT2-receptors. AB - 1. To determine which subtype(s) of 5-hydroxytryptamine (5-HT) receptor are involved in the anorectic action of quipazine, the ability of selective antagonists at 5-HT2- and 5-HT3-receptors, and an antagonist at 5-HT1-like receptors, to block this response were investigated in non-deprived rats, trained to eat a palatable diet. 2. Quipazine (0.5-8 mg kg-1, i.p.) produced a dose related reduction in the intake of palatable diet. 3. The anorectic effect of 4 mg kg-1 quipazine was antagonized by the nonselective 5-HT-receptor antagonist methysergide (5 mg kg-1, i.p.) and by the selective 5-HT2-receptor antagonists ketanserin (1 mg kg-1 and 2.5 mg kg-1, i.p.) and ritanserin (0.5 mg kg-1 and 1 mg kg-1, i.p.). The selective 5-HT3-receptor antagonist GR38032F (1 mg kg-1, i.p.) and (-)-pindolol (4 mg kg-1, i.p.), which blocks some of the effects mediated at 5-HT1-like receptors, did not block the reduction in food intake produced by this dose of quipazine. 4. None of the 5-HT-receptor antagonists had any effect on food intake when they were administered alone, suggesting that endogenous 5-HT is not involved in the tonic control of food intake under the conditions of these experiments. 5. It is concluded that the anorectic action of quipazine is mediated, at least in part, by activation of 5-HT2-receptors. PMID- 2906562 TI - The modulatory role of vascular endothelium in the interaction of agonists and antagonists with alpha-adrenoceptors in the rat aorta. AB - 1. We have examined the effect of endothelium on the antagonistic action of prazosin, doxazosin, yohimbine and phentolamine against phenylephrine, clonidine and noradrenaline. 2. The action of prazosin against phenylephrine was similar to that earlier reported against noradrenaline, acting as a non-competitive antagonist in the presence of endothelium and as a competitive antagonist in the absence of endothelium. Prazosin also acted as a non-competitive antagonist against clonidine in the absence of endothelium. 3. Doxazosin behaved in a similar way to prazosin against noradrenaline, phenylephrine and clonidine acting as a non-competitive antagonist in the presence of endothelium and as competitive antagonist after removal of endothelium. In contrast, yohimbine and phentolamine acted as competitive antagonists both in the presence and in the absence of endothelium. 4. Analysis of the concentration-response curves for noradrenaline, phenylephrine and clonidine in the presence and in the absence of endothelium showed that the affinity for all three agonists was the same but not the efficacy and the receptor reserve, both of which were lower in the presence than in the absence of endothelium. 5. The rank order of agonist potency in the absence of endothelium was noradrenaline greater than phenylephrine greater than clonidine. The rank order of antagonist potency was prazosin greater than or equal to doxazosin greater than phentolamine greater than yohimbine. 6. The results show that vascular endothelium modulates the contractile response to alpha adrenoceptor agonists and also modifies the action of the antagonists prazosin and doxazosin but not that of yohimbine and phentolamine. This effect of endothelium was related to a change in agonist efficacy and receptor reserve. These results also suggest that the alpha-adrenoceptors of the isolated aorta of the rat are predominantly, if not exclusively of the alpha 1-subtype. PMID- 2906563 TI - A comparison of the differential effects of vasoactive intestinal peptide and peptide histidine isoleucine on the vascular and capsular smooth muscle of the dog spleen. AB - 1. The actions of the two peptides, vasoactive intestinal peptide (VIP) and peptide histidine isoleucine (PHI) have been compared to that of isoprenaline on the smooth muscle systems of the isolated blood-perfused dog spleen. 2. Intra arterial injections of VIP and PHI caused graded increases in splenic arterial blood flow at constant perfusion pressure indicative of splenic arterial vasodilatation. 3. VIP was significantly more potent than PHI, with their respective molar ED50 values being 9.9 +/- 3.7 and 830 +/- 141 pmol (P less than 0.002). VIP was approximately 10 and 200 times more potent than isoprenaline and PHI respectively. 4. The maximum reduction in splenic arterial vascular resistance was the same (P greater than 0.5) in response to intra-arterial VIP and PHI, although both peptide maxima were significantly less (P less than 0.05, 0.01 respectively) than that obtained with isoprenaline. 5. Small increases in spleen volume accompanied the splenic vasodilator responses to both peptides. They were probably passive in origin, secondary to splenic arterial vasodilatation. 6. The selective beta 2-adrenoceptor antagonist, ICI 118,551, did not antagonize the splenic arterial vasodilator response to VIP or PHI but markedly attenuated the effect of isoprenaline. 7. These observations indicate that VIP and PHI, when either co-released locally or present together in the systemic circulation, may exert a differential action on different components of the circulation. PMID- 2906564 TI - [Detection of plasma AT-III and plasminogen in patients with epidemic hemorrhagic fever and its clinical significance]. PMID- 2906565 TI - Sensitivity changes to inotropic agents in rabbit atria after chronic experimental diabetes. AB - The effect of experimental diabetes on the sensitivity of isolated left atrial strips to inotropic agents was investigated in rabbits made diabetic with alloxan. After 4 weeks of diabetes no change in sensitivity was detected in response to isoproterenol or ouabain. In contrast, 15 weeks of diabetes induced a decreased sensitivity to beta-adrenergic stimulation, exhibited as a shift to the right in concentration-response curves obtained in response to isoproterenol and noradrenaline. In addition, after 15 weeks of diabetes the inotropic response to ouabain was depressed, and a small decrease in sensitivity was detected in response to forskolin. In contrast, no significant changes in the concentration response curves obtained from alpha-adrenergic stimulation by phenylephrine or calcium chloride were detected. Unlike the streptozotocin diabetic rat, which exhibits low serum thyroid hormone levels, no changes in serum thyroid hormones were detected in the alloxan diabetic rabbit. It is suggested that the increased inotropic sensitivity to alpha-adrenergic agonists observed in the diabetic rat, but not in the rabbit, may be due to low serum thyroid hormone levels. In contrast, the deleterious effects of diabetes on beta-adrenergic and ouabain sensitivity occur independently of changes in serum thyroid hormones. PMID- 2906566 TI - Beta-adrenergic receptor function and oxygen radical production in bovine pulmonary alveolar macrophages. AB - Reactive oxygen species production by bovine pulmonary alveolar macrophages was evaluated by a chemiluminescence assay utilizing luminol and opsonized zymosan. Incubation with dobutamine (5 x 10(-8) and 5 x 10(-7) M) or isoproterenol (5 x 10(-8) and 5 x 10(-7) M) prior to zymosan challenge significantly (p less than 0.05) increased the time for chemiluminescence to begin, and significantly decreased the level of maximum chemiluminescence. The agonists' inhibitory effects on maximum chemiluminescence were significantly reduced by pre-incubation with the appropriate antagonist (atenolol at 1 x 10(-6) M for dobutamine; and propranolol at 1 x 10(-6) M for isoproterenol). Salbutamol at 1 x 10(-6) M significantly reduced the level of maximum chemiluminescence only, but did not increase the time for chemiluminescence to begin. This effect was significantly reduced by the presence of the beta 2-antagonist ICI 118,551 at 1 x 10(-6) M. The results reveal the presence of beta 1- and beta 2-adrenoceptors on bovine pulmonary alveolar macrophages, and suggest that these receptors are important in the regulation of reactive oxygen species production by these cells. PMID- 2906567 TI - Characterization of a developmentally transient adrenergic depolarizing response in cultured locus coeruleus neurons. AB - The effects of iontophoretically applied noradrenaline have been tested on intracellularly recorded locus coeruleus neurons grown in explant cultures from neonatal mice. In addition to hyperpolarizing responses mediated by alpha 2 adrenergic receptors, as observed in locus coeruleus neurons in vivo and in brain slices from adult animals, alpha 1-mediated depolarizations were observed to succeed the initial hyperpolarizations in some cultures. It was shown that the depolarizing responses were only present in younger cultures, i.e., less than 26 days in vitro. In cultures less than 20 days old, all cells displayed the biphasic hyperpolarizing-depolarizing responses. Both components of the response appear to be direct, since they were present when synaptic transmission was blocked by including tetrodotoxin or by altering divalent cations in the perfusate. The depolarizing responses were frequently reduced in solutions with altered divalent cation content, and this might reflect a calcium dependency of this response. The hyperpolarizing and depolarizing components of the responses to noradrenaline were progressively blocked by increasing concentrations of the selective antagonists yohimbine and prazosin, respectively, in the dose ranges of 100 mM - 1 microM (yohimbine) and 20-200 nM (prazosin). Recent results from electrophysiological studies of locus coeruleus neurons in brain slices suggest that similar changes occur in the animal as well as in culture. It is possible that the transient depolarizing responses reflect a developmentally important enhanced responsiveness of locus coeruleus neurons during the early postnatal period. PMID- 2906568 TI - [Effects of somatostatin on coronary hemodynamics in man]. PMID- 2906569 TI - [Seroepidemiological study on amoebiasis]. PMID- 2906570 TI - [Study of dog as the animal reservoir of hemorrhagic fever with renal syndrome]. PMID- 2906571 TI - [Detection of IgG antibody in serum of hemorrhage fever with renal syndrome (HFRS) by solid-phase chemiluminescence immunoassay]. PMID- 2906572 TI - Class I and class II loci of the human major histocompatibility complex. AB - The structure of major histocompatibility complex class I (HLA-A, B and Cw) and class II (HLA-DP, DQ and DR) genes and their products is now well understood. Knowledge of the high degree of polymorphism which occurs at all MHC gene loci, primarily derived from serological studies, has largely been confirmed and extended by the application of functional, biochemical and molecular techniques. The frequencies of class I and class II antigenic products are variable between ethnic groups and also between many diseased and healthy populations. In many cases the occurrence together of two or more MHC gene products (allelic association) provides haplotypic markers specific for diseases. The function of MHC products is widely speculated upon but little is known of the precise mechanisms whereby class I and class II molecules mediate their prescribed functions of co-ordinating cell-cell interactions, their involvement in susceptibility to disease or their established role in the artificial situation of organ allografting. PMID- 2906573 TI - Population genetics and molecular biology of the childhood chronic arthropathies. AB - Recent immunogenetic studies of JRA patients have both helped to clarify subdivision into distinctive subtypes and identified those subtypes which may be related to adult rheumatic disease. Despite the variability of HLA associations from different geographic sources, a consensus appears to be emerging as to the most important associations. In addition to the HLA-DR locus, distinct associations with the HLA-DP and HLA-DQ loci have been described. Family studies have suggested an increased risk with certain haplotypes, particularly in the EOPA JRA population. Although inheritance patterns remain to be defined, recent studies with monoclonal antibodies, alloreactive T cell clones, and DNA have identified the existence of specific epitopes encoded by a variety of Ia molecules which may be more directly related to disease susceptibility. The concept of an epitope dose effect is put forward to account for the variable HLA association with disease, particularly with regard to EOPA JRA. Further developments in the definition of micropolymorphisms of Ia molecules at the genomic level as well as the possible involvement of other genetic loci, in particular T cell receptor variable gene products, should help clarify our understanding of the role of genetic factors in the aetiology of JRA. The studies of the last two decades indicate that inferences made by Carter (1969) on the 'polygenic, weakly penetrant genetic effect' in autoimmune disease are indeed applicable to JRA. PMID- 2906574 TI - [Care of patients during feverish period of epidemic hemorrhagic fever]. PMID- 2906575 TI - [Testicular autotransplantation in children. Apropos of 2 cases]. AB - The authors presents 2 observations of testicular autotransplantation at 11 and 13 years age; the 2 boys had bilateral cryptorchism. Analysis of the literature allows good conclusions for the liability of this technique with less than 20% of secondary atrophies. Particularly interesting to note 2 successful operation on children 2 years old. The indications are limited, mainly discussed is bilateral abdominal cryptorchism (mostly Prune Belly Syndrome). The autotransplantation is reserved for the normal appearance testicles with good hormonal function. The operation is preferable using inguino-iliac extra-peritoneal pass; that exploration is very important and at last only in 20% of abdominal cryptorchism could autotransplantation be considered. The malignancy transformation risk is poor if break down is done before 10 years old, however a regular and very long follow-up is necessary: Clinic, vascular, biopsies sometimes at a little doubt. Preservation of hormonal function and fertility hope represent the expected advantages; spermatic analysis are still absent because the too recent autotransplantation. As for usual testicular ectopies for sure it would be preferable to do early autotransplantation, just after 2 years of age, if this is possible. PMID- 2906576 TI - Colorimetric method for assay of serum gamma-glutamyltransferase activity with some L-gamma-glutamyl-carboxyanilides. AB - A simple method for the assay of serum gamma-glutamyltransferase activity with soluble L-gamma-glutamyl-carboxyanilides is presented. It is based on transformation of aminobenzoic acid liberated by the enzyme into colour complex with 4-dimethyl-aminobenzaldehyde or with 4-dimethylaminocinnamaldehyde in acid medium. Among three carboxyanilides studied the highest enzyme activity was noted with L-gamma-glutamyl-3-carboxyanilide and no activity with L-gamma-glutamyl-2 carboxyanilide. A good correlation was demonstrated for serum gamma glutamyltransferase activity determined by the new colorimetric method and by the standard one with L-gamma-glutamyl-3-carboxy-4-nitroanilide. PMID- 2906577 TI - Normal DNA polymorphism at the low density lipoprotein receptor (LDLR) locus associated with serum cholesterol level. AB - A restriction fragment length polymorphism (RFLP) at the low density lipoprotein receptor (LDLR) locus detectable with the restriction enzyme PvuII exhibits association with total serum cholesterol level. People who are homozygous for absence of the PvuII restriction site have a significantly higher total cholesterol level than heterozygotes (the number of homozygotes for presence of the restriction site was too small to permit meaningful comparison). This difference is significant at the 2% level. Thus, this study of sex- and age adjusted cholesterol levels in a sample of healthy people yields additional evidence and sustains our previous proposal that normal alleles at the LDLR locus contribute to the population variation in total cholesterol levels. Absence of the PvuII site appears to confer an odds ratio of approximately 2.7 for having a cholesterol level in the top quartile of the population distribution. PMID- 2906578 TI - The effect of polyunsaturated fatty acids on rat adipocyte lipogenesis: the role of protein kinase C, calcium and calmodulin. AB - Linolenic acid, a polyunsaturated fatty acid, has an insulin synergizing stimulatory effect on adipocyte lipogenesis. Since phorbol esters are also known to exert a similar effect through the activation of protein kinase C, and since they have fatty acid moieties, we investigated whether linolenic acid exerted its stimulatory effect through protein kinase C activation and whether calcium was involved in this mechanism. Our experiments show that H7, an inhibitor of protein kinase C; verapamil, a calcium blocker; and calmodulin inhibitors inhibited basal, insulin- and linolenic acid-stimulated lipogenesis. They also negated the insulin synergizing effect of linolenic acid. We conclude that linolenic acid, and possibly other unsaturated fatty acids, exert their stimulatory effect through stimulation of protein kinase C, calcium entry and calmodulin activation. These three processes are also important in maintaining basal lipogenesis. PMID- 2906579 TI - Treatment of psoriatic arthritis with sulphasalazine: a one year open study. AB - Sulphasalazine (SASP) has recently become established as an effective treatment for active rheumatoid arthritis (RA), but has not previously been used in psoriatic arthritis in which remission-inducing drugs have proved disappointing. In this one year open study, 34 patients with active psoriatic arthritis were treated with sulphasalazine. An overall favourable clinical response was observed in 23 patients (67%). Nine patients (26%) achieved a very good therapeutic response and these either had arthritis associated with spondylitis or the symmetrical type of joint disease. Evaluation at 3, 6 and 12 months showed a significant improvement in inflammatory indices including a reduction in the C reactive protein level and ESR. The drug was well-tolerated and side-effects were mild. Eight patients (23.5%) stopped the drug because of reactions and one patient with a rash was successfully desensitised. Fifty-three percent continued the drug into the second year. No apparent exacerbation of the psoriasis was observed. These results suggest that sulphasalazine is a safe and potentially effective drug in the treatment of psoriatic arthritis. A double-blind placebo controlled trial has been set up to determine its true efficacy. PMID- 2906580 TI - Treatment of atopic eczema in childhood. PMID- 2906581 TI - Betablockers in the treatment of hypertension (with special emphasis on betablockers with ISA). A review. PMID- 2906582 TI - [Some experience in antiepileptic treatment drugs monitoring in clinic]. PMID- 2906583 TI - [Neurotransmitters, hormones and portal hypertension]. PMID- 2906584 TI - [The structure of genome region containing unstable elements of human DNA]. PMID- 2906585 TI - Bivalent ligand type beta-adrenolytics related to practolol. AB - The synthesis and pharmacological evaluation of a number of symmetrical bivalent ligand type beta-adrenolytics related to practolol are reported. The best results have been observed with N,N'-bis[3-[2-hydroxy-3-[1 methylethyl)amino]propoxy]phenyl] ethanediamide. PMID- 2906586 TI - Induction of monooxygenase activity in the intestine of spot (Leiostomus xanthurus), a marine teleost, by dietary polycyclic aromatic hydrocarbons. AB - The response of intestinal monooxygenases to dietary polycyclic aromatic hydrocarbon (PAH) exposure was evaluated in spot (Leiostomus xanthurus), a marine teleost fish. Ethoxyresorufin O-deethylase (EROD) and aryl hydrocarbon hydroxylase (AHH) activities were highest in the pyloric caeca and in the proximal half of the intestine. Intestinal microsomes from fish given control diets had very low levels of EROD and AHH activities relative to those in liver. After exposure to a diet containing 10 mg of 3-methylcholanthrene/kg of food, the levels of intestinal EROD and AHH activities increased 36-fold and 17-fold, respectively, such that intestinal monooxygenase activity exceeded that of the liver, which was not induced by this treatment. A significant increase in intestinal monooxygenase activity occurred in fish receiving dietary benzo[a]pyrene (BP) at concentrations as low as 10 micrograms of BP/kg food. A 5 fold increase in intestinal AHH and EROD activities was observed within 3 hr after administration of dietary BP. A plateau in gut monooxygenase activity occurred after approximately 3 days of PAH exposure; these activities decreased to control levels within 3 days after replacing the PAH diet with the control diet. Starvation resulted in disappearance of detectable monooxygenase activity. Monoclonal antibody (MAB 1-12-3) against the major PAH-inducible cytochrome P-450 (P-450E) in the liver of the marine teleost (Stenotomus chrysops) [Park et al. Arch. Biochem. Biophys. 249, 399 (1986)] recognized a single protein band in intestinal microsomes, with Mr near 54,000, which we conclude is the spot counterpart to cytochrome P-450E.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2906587 TI - Metabolism of ethane and pentane to carbon dioxide by the rat. AB - The pulmonary excretion rates of ethane and pentane have been used as indices of lipid peroxidation. This use assumes that exhalation of these hydrocarbons is directly related to their formation rate. This is true only if the elimination (metabolism plus nonpulmonary excretion) of ethane and pentane are constant in the presence of alterations in lipid peroxidation. However, the in vivo metabolic elimination profile for pentane is unknown and it has not been established with certainty that ethane is metabolized in vivo. Radiolabeled [14C]ethane and pentane were used to study the disposition of these hydrocarbons when injected into an enclosed chamber system containing a rat. The ethane and pentane concentrations in chamber air measured as 14C radioactivity were in general agreement with more selective measurements based on GC analysis. Pentane was cleared from chamber air at a much faster rate than ethane. Approximately 50 and 19.8% of the total radioactivity added to the chamber as [14C]pentane or [14c]ethane, respectively, was recovered as carbon dioxide at the end of 8 hr. The fraction of total radioactivity recovered in urine was 7.6 and 1.0% for the pentane and ethane experiments, respectively. These results indicate unequivocally that both ethane and pentane are metabolized in the intact rat. PMID- 2906588 TI - Comparison of human and mouse liver microsomal metabolism of bromobenzene and chlorobenzene to 2- and 4-halophenols. AB - Bromobenzene is metabolized by hepatic microsomes to two different epoxide intermediates, which then rearrange to form either ortho- or para-bromophenol. A rapid and sensitive technique utilizing HPLC with electrochemical detection is presented for the quantitation of these primary bromobenzene metabolites. This analytical procedure allows selective quantitation of phenolic products of microsomal metabolism without prior extraction. Application of this assay method to the microsomal metabolism of bromobenzene and chlorobenzene revealed that three important differences exist between mice and humans regarding the metabolism of these compounds. First, human liver microsomes have a greater affinity for halobenzene biotransformation to the hepatotoxic 3,4-epoxide, as indicated by the approximately 2-fold lower Km values for para-halophenol production compared with mouse liver microsomes. Second, human liver microsomes produce the hepatotoxic metabolite at a 2-fold greater rate than mouse liver microsomes, relative to the microsomal cytochrome P-450 content. And third, human liver microsomes produce less of the nonhepatotoxic ortho-halophenol metabolites at Vmax resulting in an average ratio of the hepatotoxic: nonhepatotoxic metabolite production that is 3.5 times higher than the ratio for B6C3F1 mice. These results indicate humans preferentially metabolize halobenzenes through the hepatotoxic 3,4-epoxide pathway, suggesting that humans may be more susceptible than mice to halobenzene-induced hepatotoxicity. PMID- 2906589 TI - Metabolism of lovastatin by rat and human liver microsomes in vitro. AB - The metabolism of lovastatin (Mevacor) was examined using isolated microsomes derived from the livers of normal and phenobarbital-treated rats and from human liver samples. Incubation of lovastatin with rat liver microsomes resulted in the formation of several polar metabolites of lovastatin. The metabolites were isolated by HPLC and identified by NMR and mass spectrometry. One fraction consisted of a 2:1 mixture of 6-hydroxy-lovastatin and the rearrangement product delta 4,5-3-hydroxy lovastatin. Addition of a trace of acid to this mixture resulted in the formation of a single aromatized product, the desacyl-delta 4a,6,8-dehydro analog of lovastatin. Another microsomal metabolite was determined to be the delta 4,8a,1-3-hydroxy-lovastatin derivative. The chromatographic pattern of metabolites produced from lovastatin by human liver microsomes was similar to that obtained with rat liver microsomes. Metabolism of lovastatin by rat liver microsomes was both time and concentration dependent; optimal microsomal metabolism occurred with 0.1 mM lovastatin, whereas higher lovastatin concentrations inhibited the reaction. The open acid form of lovastatin was poorly metabolized by both the rat and the human liver microsomes. PMID- 2906590 TI - The disposition and toxicology of retinyl methyl ether in rats dosed orally. AB - In disposition studies, retinyl methyl ether (RME) was administered to rats in oral doses of 10 or 40 mg/kg. For the high dose, RME was eliminated from plasma with a terminal half-life of 19.5 hr but for the low dose the terminal phase could not be determined. For both doses, the concentrations of RME in the tissues examined (liver, spleen, adrenals, and mammary glands) were greater than those in plasma. In the adrenals of rats given the low dose, concentrations were as much as 10- to 100-fold higher. Concentrations of RME in the mammary gland, a site for chemopreventive activity, were also relatively high (about 1000 ng/g for the low dose and about 4000 ng/g for the high dose), and there was an elimination phase with a half-life of 63-81 hr. After administration of RME, the concentration of retinyl esters in the liver did not increase, and no retinyl esters were detected in the mammary gland. For toxicology studies, rats were administered 20, 40, and 80 mg/kg of RME or retinyl acetate (ROAc) daily for 28 days. The toxic effects of RME were similar to those of ROAc. At equivalent mg/kg doses, weight gain depressions, bone fractures, elevations in serum triglycerides, anemia, elevations in cholesterol in females, and reductions in serum albumin were similar.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2906591 TI - Disposition and metabolism of sodium 4-[(3-(4-acetyl-3-hydroxy-2 propylphenoxy)propyl)sulfonyl]-gamma -oxobenzenebutanoate in rats and dogs. AB - The disposition of sodium 4-[(3-(4-acetyl-3-hydroxy-2 propylphenoxy)propyl)sulfonyl]-gamma-o xo benzenebutanoate (L-648,051) was determined in rats and dogs. L-648,051 is a potent receptor antagonist for leukotriene D4 and is potentially useful in the treatment of asthma and other allergic disorders. After a dosage of 10 mg/kg iv, L-648,051 declined rapidly with a half-life of approximately 2 min in rat and dog plasma. Although the compound was well absorbed, it exhibited poor bioavailability due to efficient first-pass metabolism. In rats receiving 25, 50, and 150 mg/kg po, bioavailabilities were 0.5, 4.8, and 38.7%, respectively. In dogs, bioavailability of 10 and 50 mg/kg po was 0 and 23%, respectively. Two metabolites were identified, 4-[(3-(4-acetyl-3-hydroxy-2 propylphenoxy)propyl)sulfonyl-gamma- hydroxybenzenebutanoic acid (metabolite I), formed by ketoreduction, and 4-[(3-(4-acetyl-3-hydroxy-2 propylphenoxy)propyl)sulfonyl] benzeneacetic acid (metabolite II) formed by catabolic oxidation of the butanoic acid moiety of L-648,051. Ketoreduction resulted in the production of a chiral center and two enantiomers of metabolite I. In vitro studies suggest that rat erythrocytes formed the (+)-enantiomer exclusively. When L-648,051 was administered orally or iv to rats, both the (+)- and (-)-enantiomers were observed in the plasma. The data suggest that either two L-648,051 ketoreductases were present or that inversion of the hydroxyl stereocenter of metabolite I occurred. PMID- 2906592 TI - The physiological disposition of aerosolized 4-[(3-(4-acetyl-3-hydroxy-2 propylphenoxy)propyl)sulfonyl]-gamma -oxobenzenebutanoate (L-648,051) in rats. AB - 14C-labeled 4-[(3-(4-acetyl-3-hydroxy-2-propylphenoxy)propyl)-sulfonyl]-gamma- oxobenzenebutanoate (L-648,051) was suspended in Freon under pressure and injected into rat lungs via a tracheal cannula. The particle size of the drug was 1 to 5 microns and the mean dose was approximately 0.2 mg/kg. Levels of radioactivity in the lung/trachea declined in a monoexponential manner. Absorption, estimated from radioactivity remaining in the lung and trachea, was 73% in 1 hr and 95% in 4 hr. L-648,051 and its pharmacologically active metabolite L-657,098 (formed by ketoreduction of the butanoic acid moiety of L 648,051) accounted for 96% of the radioactivity in the lung at 10 min after the dose and 91% after 60 min. The lung:plasma concentration ratio of active drug (L 648,051 plus L-657,098) was at least 176:1 at 10 min and 17:1 at 60 min (compared with 1:1 after 2 mg/kg iv) suggesting that aerosol administration of L-648,051 in humans may result in an ideal therapeutic ratio, with high levels of pharmacologically active ingredient in the lung and low levels in the plasma. PMID- 2906593 TI - Enzymatic conjugation of hexachloro-1,3-butadiene with glutathione. Formation of 1-(glutathion-S-yl)-1,2,3,4,4-pentachlorobuta-1,3-diene and 1,4-bis(glutathion-S yl)-1,2,3,4-tetrachlorobuta-1,3-diene. AB - The glutathione-dependent metabolism of the nephrotoxin and nephrocarcinogen hexachloro-1,3-butadiene (HCBD) was investigated in subcellular fractions from rat liver and kidney. HCBD was metabolized by hepatic glutathione S-transferases to (E)- and (Z)-1-(glutathion-S-yl)-pentachlorobuta-1,3-diene (GPCB) in a ratio of 20:1, which were identified by secondary ion MS and by GC-MS after acid hydrolysis. The formation of GPCB was dependent on time and on protein and glutathione concentrations. Microsomal glutathione S-transferases from rat liver catalyzed GPCB formation more efficiently than did cytosolic glutathione S transferases; very low rates of GPCB formation were observed in kidney subcellular fractions. GPCB is also a substrate for glutathione S-transferases and is metabolized to a diglutathione conjugate, which was identified by secondary ion MS and 13C NMR spectrometry as 1,4-bis(glutathion-S-yl)-1,2,3,4 tetrachlorobuta-1,3-diene (BTCB). BTCB formation from GPCB was dependent on time and on protein, glutathione, and GPCB concentrations. Hepatic cytosol catalyzed BTCB formation more efficiently than did hepatic microsomes; significant amounts of BTCB were also formed in kidney cytosol. Hepatic formation of glutathione S conjugates, translocation of the S-conjugates to the kidney, and renal processing to form reactive intermediates may be the cause of HCBD-induced nephrotoxicity and, perhaps, nephrocarcinogenicity. PMID- 2906594 TI - Metabolism of the prodrug DEGA (N-(2,6-dimethylphenyl)-4 [[(diethylamino)acetyl]amino]benzamide) to the potent anticonvulsant LY201116 in mice. Effect of bis-(p-nitrophenyl)phosphate. AB - In mice, the diethylglycineamide analogue of LY201116, DEGA (N-(2,6 dimethylphenyl)-4-[[(diethylamino)acetyl]amino]benzamide), is metabolized by consecutive N-deethylations for form MEGA and GA; the monoethylglycineamide and glycineamide analogues of LY201116, respectively. All of these compounds are in turn hydrolyzed to form LY201116 [4-amino-N-(2,6-dimethylphenyl)benzamide]. LY201116 is N-acetylated to form the N-acetyl metabolite, NAC. NAC is also deacetylated to reform LY201116. All of the above compounds inhibit maximal electroshock-induced seizures (MES) in mice. After oral administration, the potencies of these compounds were similar at their time of peak anticonvulsant effect. However, the MES ED50 values for the above compounds 5 min after iv dosing were 43, 13, 2, and 0.5 mg/kg for DEGA, MEGA, GA, and LY201116, respectively. Similar plasma levels of LY201116 were produced in mice 5 min after iv dosing with the respective ED50 values of the above compounds, which suggested that all of the compounds produced their anticonvulsant effects via LY201116. The in vivo metabolism of DEGA and MEGA but not GA to LY201116 was inhibited by the acylamidase inhibitor bis-(p-nitrophenyl) phosphate (BNPP). Mice predosed with BNPP were not protected by DEGA and MEGA from MES-induced seizures and the plasma samples contained little or no LY201116. The metabolism of GA to LY201116 was not inhibited by BNPP, and GA was an active anticonvulsant in BNPP-pretreated mice. The apparent iv potency of DEGA increased dramatically with time after dosing, again suggesting time-dependent, metabolically mediated liberation of the more potent anticonvulsant LY201116. PMID- 2906595 TI - Sulfation of acetaminophen in isolated rat hepatocytes. Relationship to sulfate ion concentrations and intracellular levels of 3'-phosphoadenosine-5' phosphosulfate. AB - The relationships among sulfate ion concentration, rates of acetaminophen (APAP) sulfation, and intracellular levels of the cofactor for sulfation, 3' phosphoadenosine-5'-phosphosulfate (PAPS) were examined in isolated rat hepatocytes. APAP sulfation rates increased as the sulfate ion concentration was raised to 1.0 mM, after which further increases in sulfate ion concentration failed to influence rates of sulfation. Cellular PAPS levels were directly related to the sulfate ion concentration both in the presence and absence of APAP. However, PAPS levels were reduced by as much as 93% in the presence of APAP. At sulfate ion concentrations below 1.0 mM, the dependence of both rates of sulfation and levels of PAPS on the availability of sulfate ion indicates that rates of sulfation may be limited by the availability of PAPS when sulfate ion concentrations are in the physiological range. Because higher sulfate ion concentrations (greater than 1.0 mM) increased intracellular concentrations of PAPS without producing corresponding increases in APAP sulfation, phenol sulfotransferase activity may be rate limiting in the presence of high concentrations of sulfate ion. PMID- 2906596 TI - Ecdysone catabolism in the white mouse. AB - Ecdysone metabolism was investigated in the white mouse Mus musculus. It was shown to involve dehydroxylation at C-14, followed by reduction of ring B into a 6 alpha-hydroxy derivative and epimerization at C-3. PMID- 2906597 TI - Disposition of citral in male Fischer rats. AB - The disposition of citral, an essential oil occurring in many foods and fragrances, was studied in male Fischer rats after iv, po, and dermal treatments. The pattern of distribution and elimination was the same after iv or oral exposure. Urine was the major route of elimination of citral-derived radioactivity, followed by feces, 14CO2, and expired volatiles. However, after dermal exposure, relatively less of the material was eliminated in the urine and more in the feces, suggesting a role for first-pass metabolism through the skin. Citral was almost completely absorbed orally; due to its extreme volatility, much of an applied dermal dose was lost. The citral remaining on the skin was fairly well absorbed. No effect of oral dose, from 5 to 500 mg/kg, was detected on disposition. Although the feces was a minor route of excretion, approximately 25% of the administered dose was eliminated via the bile within 4 hr of an iv dose. The metabolism of citral was both rapid and extensive. Within 5 min of an iv dose, no unmetabolized citral could be detected in the blood. Repeated exposure to citral resulted in an increase in biliary elimination, without any significant change in the pattern of urinary, fecal, or exhaled excretion. This suggests that citral may induce at least one pathway of its own metabolism. The rapid metabolism and excretion of this compound suggest that significant bioaccumulation of citral would not occur. PMID- 2906598 TI - Comparative metabolic disposition of ivermectin in fat tissues of cattle, sheep, and rats. AB - In the study of the metabolic disposition of ivermectin in cattle, sheep, and rats, a group of nonpolar metabolites was detected in the fat tissues of these animals. Upon saponification or esterase treatment, these nonpolar metabolites gave rise to polar products that were similar to the ivermectin metabolites present in the liver. A hypothesis was thus proposed that the polar ivermectin metabolites produced in the liver were esterified and stored in the fat as nonpolar entities, which can be reconverted back to the polar metabolites chemically or enzymatically. To substantiate this hypothesis, the regeneration of polar metabolites from the nonpolar metabolites was studied and hydrolysis products were characterized to establish the basic structure of the alcohol portion of the metabolites. Furthermore, chromatographic comparisons were made between radiolabeled in vivo metabolites and synthetic fatty acid ester samples. These results established the general structural class of the ivermectin nonpolar metabolites and also confirmed the unusual metabolic pathway of ivermectin disposition in fat tissue. PMID- 2906599 TI - Metabolism of kadsurenone and 9,10-dihydrokadsurenone in rhesus monkeys and rat liver microsomes. AB - The metabolism of the PAF antagonists kadsurenone and tritium-labeled 9,10 dihydrokadsurenone was studied in rhesus monkeys and rat liver microsomes. The monkey metabolites of the two drugs were isolated as their glucuronide conjugates from the urine of iv dosed males. The metabolites from both monkey and microsomal metabolism were purified by reverse phase HPLC and identified by spectral (NMR, UV, and mass spectrometric) analysis. The principal pathway of biotransformation of the tritium-labeled 9,10-dihydrokadsurenone in monkeys was hydroxylation of the C-5 propyl side chain to give two metabolites, 10-hydroxy-9,10 dihydrokadsurenone and 9-hydroxy-9,10-dihydrokadsurenone. These compounds were excreted as glucuronides. Microsomal incubation of tritium-labeled 9,10 dihydrokadsurenone yielded the 10-, 9-, and 8-hydroxy-9,10-dihydrokadsurenone as major metabolites. Kadsurenone was also metabolized at the C-5 side chain, an allyl group. The monoglucuronide of 9,10-dihydroxykadsurenone was isolated from monkey urine. Spectral analysis was not definitive as to the site of conjugation, and the structure of the metabolite was assigned as the C-10 conjugate. A major metabolite of rat liver microsomal incubation of kadsurenone was 9,10 dihydroxykadsurenone. PMID- 2906600 TI - Phenylbutazone-hydroxycoumarol interactions. Effects on steady state disposition, hepatocellular distribution, and biliary excretion of (S)-acenocoumarol in rats. AB - The effect of phenylbutazone on the disposition of (S)-acenocoumarol in the rat was studied at steady state conditions of distribution and elimination. (S) Acenocoumarol was administered by constant rate infusions (1 microgram/min). The biliary excretion of 6- and 7-hydroxylated acenocoumarol was followed and the intrahepatic distribution was investigated. Phenylbutazone (50 mg/kg) increased the plasma unbound fraction about 4-fold. (S)-Acenocoumarol plasma clearance was enhanced (2.8 +/- 0.15 vs. 1.54 +/- 0.14 ml/min) but the unbound plasma clearance was reduced by 50% (67 +/- 9 vs. 140 +/- 27 ml/min). Phenylbutazone caused an intrahepatic redistribution of (S)-acenocoumarol, i.e. the drug shifted from the cytosol to the 10,000g pellet. The cytosolic unbound concentration, however, was increased. The (S)-acenocoumarol content in the microsomal fraction was not affected. The biliary excretion rate of total metabolite (free plus conjugated) comprised 50% of the (S)-acenocoumarol infusion rate in controls and was slightly stimulated (+20%) by phenylbutazone. The biliary excretion of free metabolites, however, was greatly increased (62 +/- 7 vs. 22 +/- 6 ng/min for 6-hydroxy acenocoumarol; 337 +/- 38 vs. 141 +/- 32 ng/min for 7-hydroxy-acenocoumarol). This effect is probably due to stimulation of a hepatic biliary transport system; the rate constant for transport of 7-hydroxy-acenocoumarol was enhanced 5-fold (0.107 +/- 0.03 vs. 0.021 +/- 0.007 min-1). PMID- 2906601 TI - Cyclosporine pharmacokinetics in rats and interspecies comparison in dogs, rabbits, rats, and humans. AB - The pharmacokinetics of cyclosporine, a potent immunosuppressive agent, are described for rats given 5 mg/kg iv, measuring blood concentrations by a specific HPLC method. Cyclosporine followed first-order kinetics and blood concentrations vs. time data were adequately described by a three-compartment open model system. The mean half-life of the lambda 1 phase was 0.11 hr, that of the lambda 2 phase was 1.82 hr, and the half-life of the estimated lambda 3 phase was 23.79 hr. The mean apparent volume of distribution and Vss were 5.69 and 4.54 liters/kg, respectively. The mean blood total body clearance was 3.38 ml/min/kg. The literature was reviewed to obtain comparable data from other mammalian species, and satisfactory kinetic information was found for humans, dogs, and rabbits. Interspecies variants in physiological parameters and cyclosporine pharmacokinetics were considered and treated as a property and consequence of body size (allometry), nullifying anatomical and physiological differences between species. A relationship between pharmacokinetic time (a variable in terms of chronological time) and body weight was found. It is suggested that the metabolic capacity (based on liver weight) to eliminate cyclosporine is similar in humans, rabbits, and rats, whereas the dog showed a potentially double capacity to metabolize the drug. However, metabolic and pharmacodynamic studies are also needed to predict toxicity accurately among species. PMID- 2906602 TI - Comparative study on the disposition of a new orally active dopamine prodrug, N (N-acetyl-L-methionyl)-O,O-bis(ethoxycarbonyl)dopamine (TA-870) and dopamine hydrochloride in rats and dogs. AB - The pharmacokinetics of a dopamine derivative, TA-870, and dopamine (DA) after oral administration are compared in rats and dogs. The maximum concentrations of free DA in plasma after oral administration of TA-870 were 150 ng/ml in the rat (30 mg/kg) and 234 ng/ml in the dog (33.5 mg/kg). On the contrary, the maximum plasma concentrations after oral administration of DA at an equimolar dose to TA 870 were 12 ng/ml in the rat (12 mg/kg) and 36 ng/ml in the dog (13.5 mg/kg). The AUC values of free DA in plasma after oral administration of TA-870 (30 or 33.5 mg/kg) were 4-6 times higher than those after DA in both animal species. The peak tissue levels of radioactivity in rats after oral administration of [14C]TA-870 (30 mg/kg) were also 5.5 times higher in the liver and 1-2 times higher in other tissues than those after [14C]DA dose (12 mg/kg). In rats, the main excretion route of radioactivity after oral administration of [14C]TA-870 or DA was via the urine. The total recoveries of radioactivity in the urine and feces were 91-96% of the dose within 24 hr for both compounds. Biliary excretion in rats accounted for 19.8% of the dose of [14C]TA-870 and 12.6% of the dose of [14C]DA within 24 hr. These results demonstrate that TA-870 was well absorbed from the digestive tract, extensively metabolized to dopamine, and proved to be an orally usable dopamine prodrug. PMID- 2906603 TI - Bambuterol, a carbamate ester prodrug of terbutaline, as inhibitor of cholinesterases in human blood. AB - Bambuterol, the bis-dimethyl carbamate prodrug of terbutaline, was tested for its potency in inhibiting cholinesterases in human blood. Preincubation of blood with bambuterol in the absence of thiocholine ester substrate was essential for obtaining maximal inhibition. The inhibition exerted by bambuterol after such preincubation was reversible and noncompetitive. Bambuterol was an extremely effective inhibitor of cholinesterase when butyrylthiocholine was used as substrate (I50 = 1.7 +/- 0.3 x 10(-8) M, N = 10) whereas it was 2400-fold less efficient in inhibiting cholinesterase with acetylthiocholine as substrate (I50 = 4.1 +/- 0.5 x 10(-5) M, N = 10). Because butyrylthiocholine is the preferred substrate for cholinesterase (EC 3.1.1.8) and acetylthiocholine for acetylcholinesterase (EC 3.1.1.7), these results indicate that bambuterol is a remarkably selective and potent inhibitor of cholinesterase. PMID- 2906604 TI - Studies on the metabolism of l-menthol in rats. AB - Metabolism of l-menthol in rats was investigated both in vivo and in vitro. Metabolites isolated and characterized from the urine of rats after oral administration (800 mg/kg of body weight/day) of l-menthol were the following: p menthane-3,8-diol (II), p-menthane-3,9-diol (III), 3,8-oxy-p-menthane-7 carboxylic acid (IV), and 3,8-dihyroxy-p-menthane-7-carboxylic acid (V). In vivo, the major urinary metabolites were compounds II and V. Repeated oral administration (800 mg/kg of body weight/day) of l-menthol to rats for 3 days resulted in the increase of both liver microsomal cytochrome P-450 content and NADPH-cytochrome c reductase activity by nearly 80%. Further treatment (for 7 days total) reduced their levels considerably, although the levels were still higher than the control values. Both cytochrome b5 and NADH-cytochrome c reductase levels were not changed during the 7 days of treatment. Rat liver microsomes readily converted l-menthol to p-menthane-3,8-diol (II) in the presence of NADPH and O2. This activity was significantly higher in microsomes obtained from phenobarbital (PB)-induced rats than from control microsomal preparations, whereas 3-methylcholanthrene (3-MC)-induced microsomes failed to convert l-menthol to compound II in the presence of NADPH and O2. l-Menthol elicited a type I spectrum with control (Ks = 60.6 microM) and PB-induced (Ks = 32.3 microM) microsomes whereas with 3MC-induced microsomes it produced a reverse type I spectrum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2906605 TI - Urinary metabolites of rimantadine in humans. PMID- 2906606 TI - Pharmacokinetics of cyclosporine in streptozotocin-induced diabetic rats. PMID- 2906607 TI - [Adherence to neuroleptic treatment of schizophrenic patients]. AB - Non adherence is a topical problem: about 50% of psychiatric patients do not take their medication as prescribed. Literature's overview is revealing a lack of definition of treatment adherence and the unsatisfactoriness of methods to measure it. Reasons for reluctance to take drugs include complex treatment regimen, drug presentation, duration of treatment and side-effects, most notably akathisia and akinesia. Information exchange with patients and their family about medication is also an important factor. The patient-doctor relationship appears to be a very sensitive aspect of the problem: attempting to view non adherence psychodynamically could lead to improve it. PMID- 2906608 TI - Identification of patients at low risk of dying after acute myocardial infarction, by simple clinical and submaximal exercise test criteria. AB - A consecutive series of 559 hospital survivors of acute myocardial infarction aged less than 66 years were studied; 93 were designated prospectively as low risk because they were suitable for early submaximal exercise testing and had none of the following clinical or exercise test 'risk factors': (1) angina for at least one month prior to infarction; (2) symptomatic ventricular arrhythmias, or (3) recurrent ischaemic pain, both after the first 24 h of infarction; (4) cardiac failure; (5) cardiomegaly; and (6) an abnormal exercise test (angina, ST depression or poor blood pressure response). Altogether 301 patients were exercised; their mortality over a median follow-up of 2.4 years was 10.2%, versus 24.6% in the 258 patients not exercised (P = 0.0005). Absence of clinical 'risk factors' alone, in the exercised patients, identified 156 with a mortality of 5.4% versus 15.6% in the 145 with at least one clinical 'risk factor' (P = 0.004). The fully defined low-risk group comprised 93 of the former patients who had neither clinical nor exercise test 'risk factors'. None of these patients died compared with 19 of those with at least one 'risk factor' (mortality = 14.7%; P = 0.002). Their respective rates of non-fatal reinfarction were similar and never exceeded 5% per annum. Therefore, simple clinical and exercise test criteria can positively identify low-risk patients after infarction in whom secondary prevention may be inappropriate. PMID- 2906609 TI - Renal alpha 2-adrenoceptor blockade decreases sodium and water excretion in the anesthetized rat. AB - The reported effects of renal alpha 2-adrenoceptor blockade on sodium and water excretion have been inconsistent. We therefore studied the effect of an intrarenal infusion of an alpha 2-adrenoceptor antagonist in rats undergoing two distinct levels of diuresis and natriuresis. Renal excretion of sodium and water was studied in anesthetized rats that had been unilaterally nephrectomized (right kidney) 10 days prior to the experimental day. In the presence of the lower rate of saline infusion an intrarenal infusion of the alpha 2-adrenoceptor antagonist, yohimbine, (25.6 nmol/kg per min) resulted in no change in urine volume or sodium and potassium excretion. In the presence of the modest diuresis, due to the higher level of saline infusion, intrarenal yohimbine resulted in a decrease in urine volume, sodium excretion and free water clearance. These effects of yohimbine were not found in adrenalectomized rats. The ability to demonstrate an effect of renal alpha 2-adrenoceptor blockade was dependent on the baseline level of sodium and water excretion. These results suggest that renal alpha 2 adrenoceptors may mediate the inhibition of the renal action of vasopressin by adrenal catecholamines. PMID- 2906610 TI - Mu-, delta- and kappa-opioid receptor-mediated inhibition of neurotransmitter release and adenylate cyclase activity in rat brain slices: studies with fentanyl isothiocyanate. AB - We investigated the effects of [D-Ala2,D-Leu5]enkephalin (DADLE). [D Ala2,MePhe4,Gly-ol5]enkephalin (DAGO), [D-Pen2,D-Pen5]enkephalin (DPDPE) (0.01-1 microM) and bremazocine (0.001-0.3 microM) on the electrically evoked release of radiolabelled neurotransmitters and on the dopamine (DA)-stimulated cyclic AMP efflux from superfused rat brain slices. The differential inhibitory effects of these agonists on the evoked neurotransmitter release indicate that the opioid receptors mediating presynaptic inhibition of [3H]noradrenaline (NA, cortex), [14C]acetylcholine (ACh, striatum) and [3H]DA (striatum) release represent mu, delta and kappa receptors, respectively. In agreement with this classification, preincubation (60 min) of the slices with the delta-opioid receptor-selective irreversible ligand, fentanyl isothiocyanate (FIT, 0.01-1 microM), antagonized the inhibitory effects of DADLE and DPDPE on striatal [14C]ACh release only. On the other hand, the D-1 DA receptor-stimulated cyclic AMP efflux from striatal slices appeared to be inhibited by activation of mu as well as of delta receptors. In this case, the reversible mu antagonist, naloxone (0.1 microM), fully antagonized the inhibitory effect of the mu agonist, DAGO, without changing the effect of the delta agonist DPDPE but was ineffective as an antagonist in slices pretreated with FIT (1 microM). The inhibitory effect of DAGO on the electrically evoked [3H]NA release was antagonized by naloxone whether the receptors were irreversibly blocked by FIT or not. These data not only further support the existence of independent presynaptic mu-, delta- and kappa-opioid receptors in rat brain but also evidence strongly that mu and delta receptors mediating the inhibition of DA-sensitive adenylate cyclase could share a common binding site (for naloxone and FIT) and, therefore, may represent constituents of a functional opioid receptor complex. PMID- 2906611 TI - Acute effects of direct dopamine agonists in the mouse behavioral despair test. AB - All the dopamine agonists (apomorphine, dipropylamino-5,6 dihydroxytetrahydronaphtalene, piribedil, bromocriptine, CBM 36-733) tested in the 'behavioral despair' test performed in mice had a dose-dependent anti immobility effect, with the exception of the D-1 dopamine agonist, SKF 38393. This effect occurred at doses that reduced locomotor activity and decreased colonic temperature. A profound hypothermia of the same amplitude resulted from the immersion in water of the control and apomorphine (Apo)-treated mice. The anti-immobility effect of dopamine agonists depends on the stimulation of central dopamine receptors; this effect was antagonized more easily by haloperidol than by domperidone, and dipropylamino-5,6-dihydroxytetrahydronaphtalene was more effective than amino-5,6-dihydroxytetrahydronaphtalene. Their high sensitivity to sulpiride make it likely that the receptors involved correspond to the D-4 subtype. Blockade of dopamine receptors by haloperidol for about 5 days induced a slight hypersensitivity to the Apo effects. In contrast, tolerance to Apo occurred after administration of Apo, 5 mg/kg s.c., 24 and 16 h before testing. These data might reflect the potential antidepressant activity of direct dopamine agonists. PMID- 2906612 TI - Adrenergic-induced hyperglycemia in anaesthetized rats: involvement of peripheral alpha 2-adrenoceptors. AB - The selective alpha 2-adrenoceptor agonist, UK 14.304, induces a time- and dose dependent hyperglycemic response in the anaesthetized rat. This hyperglycemia seems to be mediated through the pancreas because lesions of the pancreatic beta cells induced with streptozotocin completely abolished this hyperglycemic response to UK 14.304 while ganglionic blockade by chlorisondamine did not affect the response. The non-selective agonist, adrenaline, induces a similar hyperglycemic response which is antagonized selectivity by the alpha 2 adrenoceptor antagonist, idazoxan. Combined alpha 1- and beta-adrenoceptor blockade resulted in an increase in the alpha 2-adrenoceptor-mediated hyperglycemic response to adrenaline. Since adrenaline is known not to cross the blood-brain barrier it is concluded that alpha 2-adrenoceptor stimulation induces hyperglycemic responses through a peripheral effect that involves postsynaptic alpha 2-adrenoceptors in the pancreatic beta-cell which are linked to the inhibition of insulin release. PMID- 2906613 TI - Evidence for non-adrenergic binding sites for [3H]idazoxan in the smooth muscle of rabbit urethra. AB - The binding characteristics of [3H]idazoxan and [3H]rauwolscine, two potent alpha 2-adrenoceptor antagonists, were compared in the rabbit urethral smooth muscle. The maximal binding capacity was 6 times higher for [3H]idazoxan than for [3H]rauwolscine in male rabbits. No difference was observed for these radioligands in female rabbits. There were marked differences in the ability of alpha 2-adrenergic compounds to inhibit [3H]idazoxan and [3H]rauwolscine binding. These results were consistent with the existence of non-alpha 2-adrenoceptor sites for [3H]idazoxan in the rabbit urethral smooth muscle. PMID- 2906614 TI - D-aminophosphonovaleric acid-sensitive spontaneous giant EPSPs in immature rat hippocampal neurones. PMID- 2906615 TI - Necroses of prolactin-secreting pituitary adenomas under treatment with dopamine agonists: light microscopical and morphometric studies. AB - In order to clarify the mechanism by which prolactin-secreting adenomas reduce in size during treatment with dopamine agonists (DA), we studied altogether 18 chromophobe pituitary adenomas by carrying out light microscopical cell counting of necrobiotic alterations and necroses in photographs of semi-thin sections. Depending on hormonal activity and preoperative treatment of the patients 3 groups of adenomas were formed: 6 prolactin producing adenomas were treated with bromocriptine and lisuride (group 3). 8 cases remained preoperatively without medical treatment (group 2). For comparison, we studied 4 cases of clinically inactive pituitary adenomas (group 1). All adenomas were immunohistologically positive for prolactin. By classifying each tumor cell in one of four stages of necrotic alteration (stage 1: intact cell, stage 2: slightly condensed nucleus and shrunken cytoplasm, stage 3: necrotic cell with still visible nuclear membrane, stage 4: cell debris) we arrived at an index for necrobiotic alterations of the 18 adenomas. We found a significantly higher rate of cell necroses in DA-treated tumors compared with preoperatively untreated prolactinomas and inactive adenomas. Previous investigations in this field have revealed that a reduction in cell size may well cause the shrinkage of the prolactinomas after DA-therapy. The results presented in this paper indicate, however, that the role of necroses now needs to be given much closer attention as an additional factor. PMID- 2906616 TI - [The participation of the structures of the ventral sections of the medulla oblongata in realizing vasomotor pressor reflexes]. AB - In acute experiments on cats, under constant perfusion of tibial and small intestine vessels and after bilateral electrolytic lesion of ventral portions of the paragigantocellular nucleus a decrease of initial AP by 30-35%, perfusion pressure in tibial vessels by 30% was observed whereas the changes of AP in the small intestine vessel were insignificant. The occlusion of the common carotid artery or electrical stimulation of afferent fibers of brachial plexus exerted no effect, at that. Bilateral administration of L-glutamate into ventral portions of reticular nucleus increased the perfusion pressure in tibial vessels by 15% and in those of small intestine by 35%. Carotid sinus pressor reflex induced 1.5-fold shifts of systemic AP as compared with control values. PMID- 2906617 TI - [Hemodynamics in waking rats undergoing testicular exposure to elevated temperature]. AB - Changes of systemic and regional hemodynamic parameters of the rat during heating of the lower part of the body in 41 degrees C water and after removing of the testis from abdominal cavity, were measured with labeled microsphere technique. Experimental cryptorchism reduced the blood pressure due to a decrease in total peripheral resistance. Hyperthermia of the testis increased the heart rate. Heating of the scrotal region led to an increase in the blood flow that did not, however, reach the value of the blood flow in testis of the control unrestrained rats, thus suggesting an inadequate blood supply of the testis during heating. The inadequate blood supply of the testis under hyperthermia may be one of the factors leading to lesions of the testis. PMID- 2906618 TI - Advances in the drug management of rheumatoid arthritis. PMID- 2906619 TI - Benign partial epilepsy--treatment with sulthiame. PMID- 2906620 TI - Involvement of prostaglandins in the inhibitory response of adrenoceptor agonists in the rat isolated uterus. AB - 1. The possible involvement of intramurally generated prostaglandins in the responses produced by noradrenaline (NA), adrenaline (ADR) and salbutamol (SAL) has been investigated in the rat isolated uterus. 2. NA, ADR and SAL produced concentration-related inhibition of acetylcholine-induced tone in preparations from the proestrus, oestrus, metoestrus and dioestrus phases of the oestrous cycle, and from ovariectomized animals. 3. The cyclo-oxygenase inhibitor, flurbiprofen (FBF), enhanced uterine inhibitory response to all three agonists under the different hormonal conditions. 4. The dual inhibitor of cyclo-oxygenase and lipoxygenase, 3-amino-l-(m-trifluoromethyl)-phenyl-2-pyrazolone (BW 755C) also potentiated uterine response to NA, ADR and SAL, but the effect produced by BW 755C was similar to that achieved in the presence of FBF. 5. In contrast, the inhibition elicited by histamine and papaverine were unaffected by FBF treatment. 6. The above results provide pharmacological evidence that adrenoceptor agonists may influence prostaglandin production in the rat uterus both in the presence, and absence of the ovarian hormones. PMID- 2906621 TI - Unrecognized laceration of tibialis anterior tendon: a case report. AB - Surgical exploration of the traumatic wound is always important to allow full definition of the extent of injury. The authors report a case of a lacerated tibialis anterior tendon that was initially overlooked 8 years prior to presentation. PMID- 2906622 TI - Aberrant MN bloodgroup inheritance in a German family: a 'silent' allele? AB - By means of extensive serogenetic testing of a family, RFLP analysis and biostatistic evaluation we present evidence for the rare transmittance of a 'silent' information at the MN blood group locus in a Caucasian family. PMID- 2906623 TI - A major secretory protein from rat seminal vesicle binds ejaculated spermatozoa. AB - The rat seminal vesicle produces large amounts of a protein-rich fluid that greatly contributes to semen volume. RSV IV, a protein abundantly secreted from this gland, binds in vitro to rat epididymal spermatozoa. However, there is no evidence that this protein may have an in vivo role as a sperm-coating antigen. We report in this paper that high-molecular-weight RSV IV immunologically related proteins can be detected on ejaculated spermatozoa, but not on epididymal spermatozoa. After incubation of purified RSV IV with ejaculated spermatozoa in freshly recovered semen or with epididymal spermatozoa in a medium containing the coagulating gland secretion, sperm-bound proteins with analogous properties were detected. These results support the hypothesis that RSV IV is modified at ejaculation to an high-molecular-weight, sperm-coating antigen. PMID- 2906624 TI - A scanning electron microscopic study of the common bile duct epithelium in the rabbit during experimental biliary tract obstruction. AB - Complete biliary obstruction was induced in rabbits by distal ligation of the common bile duct (CBD). The epithelial surface of the CBD was studied with scanning electron microscopy (SEM) at 1-6 days post-ligation. Concomitant biochemical assessments and pressure measurements in the CBD were performed. SEM of non-ligated CBD showed that the epithelium is arranged in folds and clefts, the latter displaying interdigitating cellular processes. At 2 days post ligation, the epithelial clefts were focally distended showing marked dehiscence of the cellular processes with exposure of the subepithelial connective tissue layer. At 4-6 days post-ligation, extensive defects in the epithelium were observed, frequently with a sharp demarcation between intact epithelium and exposed connective tissue stroma. PMID- 2906625 TI - Determining competency to assent to neuroleptic drug treatment. PMID- 2906626 TI - Use of psychotropic drugs in alcoholism treatment: a summary. PMID- 2906627 TI - Characteristics of cell mediating spontaneous resistance to bone marrow allografts. AB - Mice of most strains show a genetically determined ability to reject foreign bone marrow grafts even after lethal irradiation. The effector cells mediating this resistance are spleen localised, lymphoid in morphology, and rapidly renewing. Two additional aspects of these cells were characterized in the present study, i.e., their sensitivity to: 1) anti-T cell and -B cell antibodies, and 2) the immunoregulator PGE2. T and B cell depleted splenocytes, or splenocytes from PGE2 pre-treated, highly resistant mice (C57Bl/6J) were transferred into irradiated, non-resistant secondary host mice (129/J) to establish whether or not they would retain their normally strong ability to spontaneously reject a third party (DBA/2) bone marrow allograft. In all cases, bone marrow seeding was assayed by enumerating the spleen colonies present in the secondary host 7 days after bone marrow grafting. Irradiated 129/J mice injected with low numbers (20 x 10(6) of untreated C57Bl/6J spleen cells prior to DBA/2 bone marrow contained 27.8 +/- 1.9 colonies/spleen, while mice injected with the same number of T and B depleted C57Bl/6J spleen cells contained significantly fewer (16.3 +/- 1.7) colonies/spleen. On the other hand, when C57Bl/6J spleen cells were incubated overnight with PGE2 prior to injection (20 x 10(6) into the 129/J hosts, they were unable to prevent the development of numerous colonies upon challenge with the DBA/2 bone marrow allograft (31.5 +/- 1.5 colonies/spleen: PGE2 pre-treated vs 16.9 +/- 2.1 colonies/spleen: non-pre-treated, control). The results demonstrate firstly, that spleen cells depleted of both Thy-1- and Ig-bearing cells appear to have concentrated for the effector cells responsible for bone marrow allograft rejection, and secondly, such effector cells could be suppressed by short-term exposure to PGE2, resulting in successful "take" of the bone marrow allograft. PMID- 2906628 TI - Murine macrophage cell line AP284 presents antigen to cloned MT4+, Lyt-2- T cells in vitro and in vivo. AB - A murine macrophage cell line AP284 that appeared to be mature in phenotype was isolated. After repeated cloning, the cell line expressed the markers Mac-1, Mac 2, Mac-3, 2.4G2, F4/80 as well as Ia antigens. Moreover, it was positive for the enzymes nonspecific esterase and acid phosphatase, negative for alkaline phosphatase and was able to phagocytize latex beads. We studied whether this cell line was able to present antigen to cloned MT4+, Lyt-2- T cells specific for methylated bovine serum albumin (mBSA) or ovalbumin (OVA). The in vitro proliferative response of the cloned T cells specific for mBSA or OVA was found to be effectively supported by AP284. This proliferation could be blocked by monoclonal antibodies against Ia determinants. AP284 also effectively presented antigen in vivo as was shown in a foot swelling assay measuring delayed type hypersensitivity (DTH) to mBSA caused by specific cloned T cells with the helper phenotype. This offers a unique model system for studying the process of antigen presentation in which both the antigen presenting cells and the T cells are monoclonal. PMID- 2906629 TI - Modulation of pathogenicity of Entamoeba histolytica by histamine. PMID- 2906630 TI - Glutamate opens Na+/K+ channels in cultured astrocytes. AB - Glial cells from different brain regions and species are depolarized by the neurotransmitter glutamate. The depolarization or, if voltage-clamped at the resting membrane potential, the inward current induced by glutamate could be due either to activation of receptor-coupled ion channels or electrogenic uptake of the transmitter. In the present study we applied the patch-clamp technique in the whole-cell recording mode to analyze glutamate-induced currents in cultured astrocytes from rat cerebral hemispheres. At the resting membrane potential, glutamate induced an inward current ranging from 40 to 300 pA. This current decreased in size with depolarization and reversed at about 0 mV. The resulting current-to-voltage curve was linear and depended strongly on the transmembrane Na+ but not on the Ca++ or Cl- gradient. In the presence of glutamate, current noise increased at potentials positive or negative from the reversal potential indicating that ionic channels are activated by glutamate. Both kainate and quisqualate mimicked the effect of glutamate. We conclude that glutamate opens a Na+/K+ channel in cultured astrocytes because of activation of a receptor which shares many properties with the neuronal kainate/quisqualate receptor. PMID- 2906631 TI - Neurons from substantia nigra increase the efficacy and potency of second messenger arising from striatal astroglia dopamine receptor. AB - Dopamine (D1) receptors were demonstrated to be present on astroglial cells from striatum in primary culture. In a cocultivation system, the astrocytes were influenced by neurons from one of their natural projection areas (substantia nigra) to increase the efficacy and potency of second messenger (cyclic AMP) from the dopamine receptor. This provides evidence for a heterogeneity among astroglia from the various brain regions with respect to the expression of receptors. PMID- 2906632 TI - Jellyfish sting resulting in severe hand ischaemia successfully treated with intra-arterial urokinase. PMID- 2906633 TI - Myocardial involvement and its response to immunosuppressive therapy in nonspecific aortoarteritis (Takayasu's disease)--a study by endomyocardial biopsy. AB - Myocardial involvement in nonspecific aortoarteritis was evaluated in 16 patients (age 7-37 years, 2 males, 14 females) with the help of endomyocardial biopsy obtained from the right ventricle using the Cordis bioptome introduced from the right femoral vein. Morphological features of myocarditis were present in 8, endocardial thickening in 2, mild to moderate myofibre hypertrophy in 11, and a normal biopsy in 3 patients. Myocarditis was present in 8/11 cases with active disease and in none with inactive disease. Five of the 8 patients with myocarditis presented with congestive cardiac failure with 3 of them having no associated hypertension or valvar involvement to account for it. Immunosuppressive therapy was given to all patients with myocarditis. Serial studies (ongoing) showed clinical, haemodynamic and morphological improvement. Myocarditis appears to occur commonly in nonspecific aortoarteritis during the acute phase of the disease and may precipitate congestive cardiac failure in some patients. Immunosuppressive therapy shows promise and merits further evaluation. PMID- 2906634 TI - Beta-adrenoceptor antagonist-induced psoriasiform eruption. Clinical and pathogenetic aspects. AB - A number of beta-adrenoceptor blocking drugs have been reported to induce a papulosquamous eruption which resembles psoriasis. We report distinctive clinical, histopathologic, immunocytochemical, and electron microscopic features in beta-blocker-induced psoriasiform eruptions that differentiate this syndrome from psoriasis. Preliminary data suggest that biopsy specimens from eruptions caused by beta 1-selective adrenoceptor blocking agents (metoprolol and atenolol) were characterized by excessive degranulation of the neutrophils in the dermis, while the nonselective beta blockers (propranolol, nadolol, and sotalol) were marked by excessive release of proteolytic enzymes from macrophages, which are thought to possess beta 2-adrenergic receptors. Surprisingly, excessive release of enzymes by lymphocytes were noted in both the beta 1-selective and in the nonselective induced syndromes. It is believed that excessive lysosomal enzyme release by neutrophils, lymphocytes, and macrophages is responsible for the presence of basal keratinocyte herniations, which have previously been shown to correlate with hyperproliferation and psoriasiform changes, as well as with the presence of excessive proteolytic enzymes in the skin. It is postulated that the beta-blocker-induced syndrome may result from enhanced proliferation, motility, and activity of lymphocytes, neutrophils, and cells of the macrophage-Langerhans cell series, stemming from depressed intracellular cyclic adenosine monophosphate levels caused by the beta blockade. PMID- 2906635 TI - On the psychopathology of patients with disorders in the descent of the testis. AB - The authors deal with disorders in the descent of the testis and analyse the causes and manifestations from the point of view of fertility and indications to medical treatment or early surgery. Thirty-nine patients were examined and diagnosed as unilateral or bilateral cryptorchism and retention of the testis. The spermatogenetic functions in individual diagnosis and type of operation are described. They wish to ascertain a mutual connection between sexual function and neurotic symptoms in operated patients with regard to the 3 diagnostic groups. PMID- 2906636 TI - Mitochondrial DNA variability in Drosophila simulans: quasi absence of polymorphism within each of the three cytoplasmic races. AB - Nucleotide variability of mtDNA extracted from 144 isofemale lines collected in the whole range of D. simulans was analysed with 10-15 restriction enzymes and 73 lines were studied using one or a few enzymes. All clones were distributed into 3 mitochondrial genomes, siI, siII and siIII. These types are allopatric and can define geographic races. Mixed populations occur only in Madagascar and Reunion, where siII and siIII are found together. Among 40 sites detected with 10 enzymes, the variability of the coding region is extremely low, with one or no polymorphic restriction sites depending on the type. The control A + T-rich region is more variable in length and in restriction sites, and allows subtypes to be designated. Several lines were heteroplasmic for the length of the genome. These results are relevant to the evolutionary history of the species, its recent worldwide extension and to probable founder effects at the origin of each of the three types. PMID- 2906637 TI - Localization of L-glutamate decarboxylase immunoreactivity in the major pelvic ganglion and in the coeliac-superior mesenteric ganglion complex of the rat. AB - The localization of L-glutamate decarboxylase (GAD), the GABA-synthesizing enzyme, was studied in the rat major pelvic ganglion and in the coeliac-superior mesenteric ganglion complex by indirect immunofluorescence technique with a specific antiserum raised in rabbits. GAD immunoreactivity was demonstrated in small cells of these ganglia. The GAD-immunoreactive small cells were 10-20 microns in diameter and formed clusters or occurred as solitary cells. The principal neurons were non-reactive but they were surrounded by immunoreactive processes. Studies on colocalization of GAD with tyrosine hydroxylase (TH), the rate-limiting enzyme of the catecholamine synthesis, in the major pelvic ganglion and in the coeliac-superior mesenteric ganglion complex indicated that all GAD immunoreactive small cells were also labelled with TH. In the major pelvic ganglion all TH-immunoreactive SIF cells were also immunoreactive for GAD. However, in the coeliac-superior mesenteric ganglion complex there occurred TH immunoreactive small cells which showed no immunoreactivity to GAD. It is suggested that the small GAD-immunoreactive cells represent small intensely fluorescent (SIF) cells. PMID- 2906638 TI - Biochemical and developmental effects in rats following in utero exposure to acrylonitrile: a preliminary report. PMID- 2906639 TI - Genomic analysis identifies class II mismatches in serologically DR-compatible human renal allografts. AB - Many studies, including those from our own center, have shown that matching the donor and recipient for HLA-DR antigens has a beneficial effect on the outcome of cadaveric renal transplantation. However, cases of irreversible graft rejection are sometimes seen in patients who have received an HLA-DR-compatible kidney, suggesting that serologic compatibility for HLA-DR may not always ensure reduced alloreactivity toward the graft. We have examined a number of recipients and their serologically DR-compatible cadaveric donors by Southern blotting and hybridization with locus specific HLA class II probes in order to determine whether in these patients there were class II mismatches that had been undetected by serology. The results show that the analysis of DR beta restriction fragment patterns does little more than complement and confirm the serologic identification of HLA-DR. Hybridization with DQ alpha and DQ beta probes, however, significantly extends the number of DQ specificities that can be detected and suggests that DQ mismatches in DR-compatible donor-recipient pairs may be more common than previously supposed, although it is not possible to draw any conclusions on the influence of DQ incompatibilities in the presence of DR compatibility on graft outcome. PMID- 2906640 TI - Cyclin mRNA and protein expression in recombinant interleukin 2-stimulated cloned murine T lymphocytes. AB - Expression of cyclin, a non-histone nuclear protein, during recombinant interleukin 2 (rIL2)-driven cell-cycle progression of cloned T lymphocytes has been assessed. We found that expression of cyclin protein, as detected by immunofluorescence, is tightly associated with proliferation, and not merely S phase, of L2 cells stimulated with rIL2. Cyclin immunofluorescence was detected in all cell-cycle phases (G1/S/G2/M, as detected by flow cytometry) of proliferating L2 cells. Accumulation of cyclin mRNA levels was induced as early as 1 h after stimulation, was maximal at 25-49 h, and remained elevated throughout stimulation, as detected by Northern blot analysis. A cDNA-encoding murine cyclin was cloned from a cDNA library prepared from IL2-stimulated cloned T cells. The sequence of the 5' end of the murine cyclin cDNA was determined and found to be 88% and 82% similar to the sequences of cDNA clones encoding rat and human cyclin, respectively. The present studies demonstrate that cyclin protein and mRNA accumulation are highly regulated during IL2-induced proliferation of a cloned T cell. These data provide a framework for addressing the molecular mechanisms regulating cyclin gene expression during cellular proliferation. PMID- 2906641 TI - Use of supplemented Stainer-Scholte broth for the isolation of Bordetella pertussis from clinical material. AB - The use of Stainer-Scholte broth supplemented with (2,6-O-dimethyl)beta cyclodextrin (heptakis) for the isolation of Bordetella pertussis from clinical specimens was evaluated with 3,632 nasal swabs from children and adults with suspected whooping cough or from their family contacts. The liquid enrichment medium was subcultured on charcoal agar with 10% defibrinated horse blood. Charcoal agar and soft charcoal agar served as the standard procedure to detect B. pertussis. We isolated 772 strains of B. pertussis (21%). Charcoal agar alone detected 87% of all strains (n = 668), soft charcoal agar grew 78% (n = 602), and 637 strains (83%) were isolated when Stainer-Scholte broth with heptakis was used. We detected 590 isolates with all three media. Whereas 65 strains grew only on charcoal agar, 27 strains were detected by soft charcoal agar. Supplemented Stainer-Scholte broth allowed the isolation of an additional 77 strains which did not primarily grow on charcoal media (P less than 0.05). Our data indicate that Stainer-Scholte medium supplemented with heptakis can be effectively used as an enrichment medium for detection of B. pertussis in clinical specimens. PMID- 2906642 TI - Comparison of modified Bordet-Gengou and modified Regan-Lowe media for the isolation of Bordetella pertussis and Bordetella parapertussis. AB - Culture and fluorescent-antibody methods for detection of Bordetella species were evaluated by two state public health laboratories. Field-inoculated plates of Regan-Lowe agar medium were most useful if incubation was initiated on the day of collection. Regan-Lowe and Bordet-Gengou media were comparable for subculturing nasopharyngeal specimens that were transported and enriched in half-strength Regan-Lowe agar. Maximum sensitivity was achieved when the media were used in parallel. Fluorescent-antibody-stained smears of nasopharyngeal specimens were more sensitive for detection of Bordetella pertussis than for detection of Bordetella parapertussis. The fluorescent-antibody method, however, was too insensitive for use without culture. PMID- 2906643 TI - Desmethyldiazepam pharmacokinetics: studies following intravenous and oral desmethyldiazepam, oral clorazepate, and intravenous diazepam. AB - After single 10-mg intravenous (IV) doses of desmethyldiazepam (DMDZ) to 12 healthy human volunteers, (mean age, 62 years) blood samples were obtained over the next 14 or more days. Mean kinetic variables were volume of distribution (Vd), 90 liters; elimination half-life (t1/2), 93 hours; and clearance, 12.3 mL/min. Vd was significantly correlated with body weight (r = .73, P less than .01) and with percent ideal body weight (r = .91, P less than .001). Eleven of the same subjects also received 5- to 15-mg doses of IV diazepam (DZ). Mean kinetic variables were Vd, 180 liters; t1/2, 83 hours; and clearance, 28 mL/min. Clearances of DZ and DMDZ were significantly correlated (r = .73, P less than .02). Based on area analysis, the extent of conversion of DZ to systemic DMDZ averaged 53%. After oral administration of DMDZ in tablet form (10 mg), or of clorazepate dipotassium in capsule form (15 mg), systemic availability of DMDZ from each of the oral dosage forms was not significantly different from 100%. PMID- 2906644 TI - [Comparative study of levobunolol and timolol in the treatment of chronic open angle glaucoma and chronic ocular hypertension]. AB - Forty patients with chronic open-angle glaucoma or ocular hypertension participated in this randomized double-masked clinical trial. The patients instilled either 0.5% Levobunolol or 0.5% Timolol into each eye twice daily for three months. Levobunolol produced an overall decrease in mean intraocular pressure of approximately 7 mmHg, while Timolol produced an overall decrease of approximately 5 mmHg but no significant difference has been proved. Intraocular pressure was inadequately controlled in five patients in each treatment group. Both drugs caused heart rate decreases that were judged to be of limited clinical significance. Levobunolol was found to be as safe and effective as Timolol for the treatment of patients with open-angle glaucoma as for those with chronic ocular hypertension. PMID- 2906645 TI - Adverse effects with oral 5-aminosalicyclic acid. AB - Two patients with ulcerative colitis and a past history of allergic reactions to sulfasalazine had similar reactions when treated with 5-aminosalicylic acid. This suggests that, at least in some patients, the adverse effects of sulfasalazine are due to 5-aminosalicylic acid rather than sulfapyridine. Desensitization to sulfasalazine was successfully carried out in one patient but was not attempted in a second. PMID- 2906646 TI - Human ecology related to urban mosquito-borne diseases in countries of South East Asia region. PMID- 2906647 TI - Malaria as anthropo-ecosystem. Part I: General concept. PMID- 2906648 TI - Limitation of infarct size after acute myocardial infarction. PMID- 2906649 TI - [Biochemistry of Parkinson's disease]. PMID- 2906650 TI - Recommendation for the measurement of "alanine aminopeptidase" in urine. AB - A method is recommended for the measurement of the catalytic concentration of alanine aminopeptidase in the urine of man, rat, and dog, using L-alanine-4 nitroanilide as substrate. In currently used methods, substrate concentrations between 1.7 and 2.0 mmol/l are used. Kinetic experiments show, however, that the reaction is inhibited by substrate concentrations exceeding 0.8 (man), 0.3 (rat) and 0.5 mmol/l (dog); these concentrations lie in the range of the Km values. Assay conditions were therefore chosen to give the lowest possible Km. The Km value depends on the type of buffer, and it increases with pH and temperature. The recommended assay conditions are: triethanolamine buffer 70 mmol/l, pH 7.6; L alanine-4-nitroanilide concentrations depending on the species; incubation temperature 25 degrees C. PMID- 2906651 TI - The story of Bacillus thuringiensis var. israelensis (B.t.i.). AB - The isolation and the characteristics of Bacillus thuringiensis var. israelensis is reviewed. Included in the review are full descriptions of the nomenclature, mosquito target range of this potent mosquitocidal bacterium, as well as the genetics and biochemistry of the toxins. PMID- 2906652 TI - Portable, battery-powered aspirators for collecting adult mosquitoes. PMID- 2906653 TI - Efficacy of Bay Sir 8514, an insect growth regulator, against Psorophora columbiae and Anopheles quadrimaculatus in small plot and field trials. AB - Four formulations of an insect growth regulator, Bay Sir 8514 (a benzoylurea compound), were tested against 2 species of riceland mosquito larvae, Anopheles quadrimaculatus and Psorophora columbiae. Formulations of 25% WP, 0.5% G and 065 EC (65 g/liter) were tested at dosages of 14, 28, 56, and 84 g ai/ha in small plots. The 14 g ai/ha rate was ineffective for all formulations while the 28, 56 and 84 g ai/ha provided 100% mortality through 48 hr posttreatment. The 84 g ai/ha rate gave complete control through 7 days posttreatment. A 4 F formulation was applied aerially at rates of 24.9 and 49 g ai/ha to a 9.7 ha rice field. The 24.5 g ai/ha rate provided marginal control at 24 hr posttreatment but failed to control larvae at 48 hr. At 49 g ai/ha, the material provided control through the 48 hr posttreatment. PMID- 2906654 TI - Use of an artificial bromeliad to show the importance of color value in restricting colonization of bromeliads by Aedes aegypti and Culex quinquefasciatus. AB - An artificial bromeliad was developed which, painted and containing an infusion water, elicited ovipositional response by caged adult Aedes aegypti, Culex quinquefasciatus, Wyeomyia vanduzeei and Wy. mitchellii. Comparison was made of the ovipositional response of adults of the four mosquito species to artificial bromeliads painted black, white, dark green and deep blue. Adult Ae, aegypti and Wy. vanduzeei did not discriminate significantly between white, dark green and deep blue, but whereas Ae. aegypti showed a preference for black, Wy. vanduzeei showed an aversion to black. Adult Wy. mitchelli responded similarly to Wy. vanduzeei except that although deep blue was preferred to black, it elicited a significantly weaker response than did dark green and white. Adult Cx. quinquefasciatus responded similarly to Ae. aegypti but did not show a significant preference for black over dark green. The high color value (i.e., lightness) of natural bromeliad leaves is likely to deter oviposition by adult Ae. aegypti and Cx quinquefasciatus in favor of competing oviposition sites of lower color value. PMID- 2906655 TI - A telescoping collection cup changer for insect traps. AB - A description is provided of a time interval insect sampler that has been used in suction traps but would also be useful with light traps. The device is capable of taking 27 successive samples. Principle of operation involves 2 telescoping concentric cylinders. The collection cups, mounted in the motor driven inner cylinder, are closed by the wall of the outer cylinder as the inner cylinder spirals inward about a helix screw. PMID- 2906656 TI - The use of an animal-baited net trap for collecting mosquitoes during western equine encephalitis investigations in Argentina. AB - A large net trap was used to sample mosquito populations attracted to horses at three sites each in Santa Fe and Rio Negro Provinces, Argentina, during the austral summer of 1984. These provinces, as well as others in Argentina, were affected by a severe epizootic of western equine encephalitis (WEE) during 1982 83. Totals of 2,752 and 6,929 mosquitoes were collected in Santa Fe and Rio Negro Provinces during five and three trap nights, respectively. Culex mosquitoes of the subgenus Culex were predominant (45.8% of total) in the Santa Fe collections, although Aedes albifasciatus also was prevalent (21.7%). The latter species was predominant (95.7% of total) in the Rio Negro collections. The mosquito fauna was less complex (minimum of 6 species) in Rio Negro Province as compared to Santa Fe Province (minimum of 18 species). The advantages of the net trap indicate that this trap can become a useful tool in arbovirus ecology studies in other areas. PMID- 2906658 TI - A revised list of the mosquitoes of North Dakota, including new additions to the fauna. AB - An up-to-date list of the mosquitoes known to occur in North Dakota is given. It includes 38 species in 8 genera. Aedes hendersoni, Ae. melanimon, and Culiseta minnesotae are being reported for the first time. In addition, 6 other species that probably belong to the state's fauna are discussed. PMID- 2906657 TI - Mathematical models of the effectiveness and persistence of mosquito repellents. AB - Two models of the effectiveness and persistence of mosquito repellents on the skin were developed from published functions and data. The probit plane model, Y = a + b1X1 + b2X2, relates the response (Y, in probits) of the mosquito test population to the log dose (X1) of repellent applied and the test period, or elapsed time from the time of application (X2). The exponential decay model, Z = X1 + (b2/b1)X2, estimates the repellent residue (log-1 Z) from X1 and X2. The models were validated with original data from tests of deet (N,N-diethyl-3 methylbenzamide) and ethyl hexanediol (2-ethyl-1,3-hexanediol) on the forearm against the yellow fever mosquito, Aedes aegypti. The probit plane model was evaluated as Y = 8.83 + 1.56 X1-0.69X2 for deet and Y = 8.67 + 1.68X1 - 0.92X2 for ethyl hexanediol when X1 is in log mg/cm2 and X2 is in hours. The exponential decay model was evaluated as Z = X1 - 0.45X2 for deet and Z = X1 - 0.55X2 for ethyl hexanediol. The decay constant (lambda) and half-life (t1/2) were estimated as 1.03 hr-1 and 0.67 hr for deet and 1.26 hr-1 and 0.55 hr for ethyl hexanediol from the slope parameter (b2/b1) of the decay model. Applicable correlation coefficients, standard errors and confidence limits are given. The introduction of these models of the pharmacodynamics of mosquito repellents is a step toward establishing a rational basis for the research, development, testing and evaluation of repellents and for their regulation by the government.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2906659 TI - Density estimation and population growth of mosquitofish (Gambusia affinis) in rice fields. AB - Mark-release-recapture estimation of population density was performed with mosquitofish in a rice field habitat. Regression analysis showed a relationship between absolute density and mean number of fish per trap. Trap counts were converted to density estimates with data from several fields and growth curves were calculated to describe seasonal growth of mosquitofish populations at three different initial stocking rates. The calculated curves showed a good correspondence to field populations of mosquitofish. PMID- 2906660 TI - A comparison of female Culiseta melanura captured in New Jersey and CDC light traps in southeastern Massachusetts. PMID- 2906661 TI - A blood meal analysis of engorged mosquitoes found in Rift Valley fever epizootics area in Kenya. PMID- 2906662 TI - Habitat selection strategies of mosquitoes inhabiting citrus irrigation furrows. AB - The mosquitoes Aedes vexans, Psorophora columbiae and Psorophora howardii have recently extended their habitat distribution into citrus irrigation furrows in coastal southeastern Florida. Oviposition site selection was examined by correlating species abundances with water depths due to rainfall or flood irrigation. Psorophora columbiae and Ps. howardii oviposited low in furrows, shared similar distributional relationships to water depths and were hatched by rainfall or irrigation. Aedes vexans oviposted higher in the citrus furrow, showed a different relationship to water depth and were hatched only by flood irrigation. PMID- 2906663 TI - Species composition and feeding success of mosquitoes attracted to caged dogs in Indiana. AB - A field study using caged dogs in mosquito bait traps was conducted in eastcentral Indiana to determine the species composition of mosquitoes coming to feed. Fourteen species of mosquitoes from 5 genera were collected; Aedes trivittatus predominated. Feeding success rates were measured as the percentage of mosquitoes collected that had a fresh blood meal. The species having the highest rates were: Culex erraticus, Aedes stimulans and Ae. trivittatus. Aedes vexans and Cx. pipiens/restuans had markedly lower feeding success rates. A New Jersey light trap operated at the same site each year yielded a different species composition. Because of its propensity for feeding on dogs, Ae. trivittatus may be considered as a major potential vector of heartworm disease in dogs, even where it is one of several possible vector species present in abundance. PMID- 2906664 TI - Laboratory colonization of Mansonia uniformis, Ma. indiana and Ma. bonneae in Malaysia. AB - Methods are described for the laboratory colonization of Mansonia uniformis, Ma. indiana and Ma. bonneae in Malaysia. Gravid females oviposited in 500 ml beakers with a layer of water covered with small leaves of Salvinia. Newly hatched larvae were set up in a basal medium of guinea pig dung and water or liver powder, yeast powder and water. Larvae attached to aquatic plants or 'Keaykolour' ruffia snow white paper. The cultures with paper gave better yields than those with plants. Production of Ma. uniformis was higher than the other two species. Twelve generations of Ma. uniformis and 11 generations of Ma. indiana and Ma. bonneae were monitored in the laboratory. PMID- 2906665 TI - Man-mosquito contact at Kowanyama, northern Queensland, Australia. AB - A method employing ANOVA is presented to quantify man-mosquito contact at Kowanyama, based on human bait collections indoors in light, indoors in darkness and outdoors in darkness. No shifts in feeding behavior were noted during the transitional, dry or wet seasons of 1974-75. Anopheles bancroftii fed in significantly greater numbers indoors in darkness; An. amictus, An. annulipes, An. farauti, An. meraukensis, Aedes normanensis, Ae. kochi, Ae. lineatopennis, Ae. vigilax and Culex annulirostris fed outdoors; Mansonia uniformis fed equally well in the 3 situations tested whereas Cx. quinquefasciatus primarily fed indoors. PMID- 2906666 TI - Tests of ultrasonic emissions on mosquito attraction to hosts in a flight chamber. AB - Five ultrasonic devices generating fundamental frequencies of 20-70 kHz were tested for their efficacy in repelling mosquitoes. Four species (Anopheles quadrimaculatus, Aedes aegypti, Ae. triseriatus and Haemagogus equinus), were used in a flight chamber in which females must fly upwind against the direction of the sound waves and around the ultrasonic devices to reach a trap downwind of a source of human breath and skin emanations. Repellency was rated by the number of mosquitoes entering the trap during a series of 5 min tests. For all species there was no significant difference between the numbers trapped when the devices were switched on or off, when all devices were tested simultaneously. Tests of individual devices against Ae. aegypti also failed to show a repellent effect. PMID- 2906667 TI - Trials with portable screen rooms modified for use as animal-baited net traps for mosquito collection. AB - Trials in Larimer County, Colorado during July and August 1984, with recreational screen rooms modified as large animal-baited mosquito traps are described. The two units tested are free-standing, portable and require no external support. In all-night trials, 462.5 mosquitoes/trap night were captured with horse bait compared with 367/trap night with CDC light traps. In 2-hour evening comparisons, mosquitoes collected per trapping period totalled 416 for horse-bait traps, 132 for light traps, and 93 for human-bait traps. Animal-baited screen rooms offer an alternative to existing methods for mosquito surveillance. PMID- 2906668 TI - The compatibility of methoprene with the mosquito fungus Culicinomyces clavisporus. PMID- 2906669 TI - Devices for sampling and sorting immature Coquillettidia perturbans. PMID- 2906670 TI - Isolation of California encephalitis serotype from mosquitoes collected in Manitoba, Canada. PMID- 2906671 TI - Rapid determination of glycogen and sugars in mosquitoes. AB - A method is presented for rapid determination of glycogen and sugars in individual mosquitoes. It is suitable for large scale field studies of correlations between nutritional status and behavior. The method also describes a one step procedure for total carbohydrates and the determination of nectar sugars and the hemolymph sugar trehalose. PMID- 2906672 TI - Rapid determination of total lipids in mosquitoes. AB - Total lipids in individual mosquitoes can be determined by extraction with chloroform-methanol followed by reaction with sulfuric acid and a vanillin phosphoric acid reagent. By subtracting the lipids determined in a starved population, the method is suitable to establish variations of lipid reserves in field populations. PMID- 2906674 TI - The measurement of adult mosquito population changes--some considerations. AB - Day-to-day changes in adult mosquito populations are difficult to measure due to the interactions between specific mosquito behavior, environmental influences upon behavior, and the mode of operation of the sampling technique. Mosquito responses to terrain features and various meteorological factors are briefly summarized with the object of improving our understanding of the samples provided by several classes of sampling techniques. The two major environmental influences upon the composition of a sample are the terrain features and several meteorological factors. As each sampling site is unique, a sample provides little direct information of the numbers of mosquitoes within the much broader area it is supposed to represent but it can reflect population changes at the site. However, the population changes usually are masked by meteorological effects upon flight activity. Data from Florida field studies were utilized to adjust trap catches to compensate for meteorological conditions during the catch period to provide more standard samples. PMID- 2906673 TI - Efficacy and field evaluation of Bacillus thuringiensis (H-14) and B. sphaericus against floodwater mosquitoes in California. AB - The microbial control agents Bacillus thuringiensis (H-14) and B. sphaericus were evaluated in laboratory and field against Psorophora columbiae. Bacillus sphaericus strain 2362 was also tested in the field against Aedes melanimon. Psorophora columbiae was slightly more susceptible than Culex quinquefasciatus to active strains of B. sphaericus. The LC90 for active strains ranged from 0.013 to 0.069 mg/liter. In field trials, aqueous suspensions of primary powder of B. sphaericus 2362 and 1593 yielded 98-99% reduction in larvae at the rates of 0.1 to 0.25 lb/acre of the primary powder. Granular formulations of Bt (H-14) were evaluated against Ps. columbiae, yielding 96-99% control of larvae at rates ranging from 1 to 10 lb/acre of the granules, depending on the potency and type of the formulations. Aedes melanimon was slightly less susceptible than Ps. columbiae to B. sphaericus 2362. In warmer water a rate of 0.25 lb/acre of the primary powder yielded 88% control, while this same rate in cool weather yielded only 4% reduction. A rate of 0.5 lb/acre of the primary powder was needed to obtain 94% control of larvae in cool weather. PMID- 2906675 TI - Mortality and survival patterns for the immature stages of Psorophora columbiae. AB - To determine the patterns of Psorophora columbiae survival and mortality, methods were employed that involved the simultaneous use of laboratory-reared cohorts, predator-exclusion cages, and field estimates of larval dynamics. Laboratory studies indicated that the maximum daily survival averaged from 0.92 for day-old larvae to 1.0 for the older age classes with no significant differences (P greater than 0.05) in survival among days. Data from predator-exclusion cages indicated that mortality inflicted by factors other than predation was significantly (P less than 0.05) more intense in the younger age classes and the relatively few individuals that survived to the older age classes had a high expectation of successful emergence. A quantitative estimate of the mortality inflicted on Ps. columbiae larvae by all indigenous natural enemies indicated that mortality rates were higher in the older age classes. This supports the view that the predator complex is a major source of irreplaceable mortality for immature mosquitoes inhabiting Louisiana rice fields. PMID- 2906676 TI - Five new mosquito larvicidal strains of Bacillus sphaericus from non-mosquito origins. AB - Five new strains of Bacillus sphaericus having larvicidal activity similar to that of strains 1593 and 2362 are described. These strains were isolated from caterpillars or grasshoppers, but have no insecticidal activity toward these insects. PMID- 2906677 TI - A dredge sampler for mosquito larvae. PMID- 2906678 TI - Toxorhynchites moctezuma, a potential biological control agent in Trinidad and Tobago, W. I. PMID- 2906679 TI - Factors affecting distribution of Bacillus thuringiensis serotype H-14 during flooding of rice fields. PMID- 2906680 TI - Activity of an avermectin insecticide, Abamectin (MK-936), against mosquitoes and chironomid midges in the laboratory. PMID- 2906681 TI - Development of a floating bioassay container for mosquito larvae. PMID- 2906682 TI - The future of mosquito-borne diseases in the world. AB - The future of mosquito-borne diseases will depend on the improvements and implementation of chemotherapy and vaccination, as well as on biological and integrated control measures. Bacillus thuringiensis H-14, B. sphaericus, Lagenidium giganteum and other fungi are promising biological mosquito control agents. Other control measures include parasitoids, nematodes, larvivorous fish, Toxorhynchites mosquitoes, insect viruses, growth hormones, sex attractants, natural products, sanitation, and water management. Vector control should be combined with training of personnel and carried out on an international scale. PMID- 2906683 TI - Laboratory bionomics of Tripteroides aranoides. AB - Tripteroides aranoides was colonized in the laboratory. Total duration of the immature stages was ca. 3 weeks at 28 degrees C, L:D = 15.5:8.5 with an ample food supply. Retardation of 4th instar development was observed in larvae fed on insufficient food. Females were autogenous for the first clutch of eggs and required a blood meal for maturation of the second clutch. Mating was initiated in flight and copulation occurred on the cage wall. Gravid females hovered in small oblique loops above water in bamboo cups, whereupon a white egg appeared at the abdominal tip, which was propelled by the swing of the abdomen towards water surface. The females propelled eggs in the same manner into small apertures (11 x 4 mm) bored in bamboo. PMID- 2906684 TI - Effects of sprinkle irrigation on the occurrence and abundance of Psorophora columbiae eggs in ricelands. AB - Low-pressure sprinkler irrigation was investigated as to its potential influence on the frequency of occurrence and relative abundance of Psorophora columbiae eggs in Texas ricelands. Analysis of egg sampling data collected from soybean, rice and sorghum field sites subjected to either sprinkle or flood irrigation practices during 1982-83 indicated no significant differences in either the frequency of occurrence or relative abundance of Ps. columbiae eggs in the various sites. Data collected during 1984 indicate that the amount of water applied to a field by a sprinkler system will have some influence on the numbers of Ps. columbiae eggs occurring in the field. The frequency of occurrence and relative abundance of Ps. columbiae eggs occurring in field sites sprinkle irrigated at full-pan evaporation rates (i.e., all moisture in the soil lost to evaporation was replenished via irrigation) were significantly higher than was the case in the sites irrigated at half-pan and quarter-pan rates. PMID- 2906685 TI - The effects of selected rice and soybean pesticides on the eggs of Psorophora columbiae. AB - Twenty-five pesticides used in the production of rice and soybeans in Texas were tested in the laboratory to determine their toxicity to the eggs of Psorophora columbiae. A reduction in hatching rate occurred when eggs were treated with a herbicide formulation containing thiobencarb and with one containing a tank mixture of propanil and molinate. A carbaryl formulation induced hatching of eggs prior to their exposure to the hatching stimulus. Reduced survival to second instar of larvae hatching from treated eggs was observed with insecticide formulations of acephate, carbofuran, malathion, methyl parathion and toxaphene; a fungicide formulation of triphenyltin hydroxide and the tank mixture of the herbicides, propanil and molinate. PMID- 2906686 TI - Establishment and recycling of Romanomermis culicivorax (Nematoda: Mermithidae) in Louisiana ricelands. AB - The postparasitic stage of Romanomermis culicivorax, applied at dosage rates of 0.025 and 0.05 g/m2, was able to establish, recycle and overwinter in a riceland habit in southern Louisiana. Percent parasitism ranged from 0 to 54.1% during the 22-month study. Parasitism of Psorophora columbiae larvae was significantly greater (P less than 0.05) along levee ditches than in the central portions of the fallow riceland plots on 3 of 4 sampling dates in 1983. As percent parasitism increased within the population of Ps. columbiae located in bioassay containers, the degree of superparasitism also increased. PMID- 2906687 TI - Evaluation of cyfluthrin as a ULV cold aerosol against caged mosquitoes. AB - Cyfluthrin was evaluated against caged mosquitoes using a truck-mounted Leco HD model ULV cold aerosol generator and the results were compared to the effectiveness of malathion. Calculated effective dosages (ED) for 90% and 95% control with cyfluthrin against Aedes taenorhynchus were 0.2 and 0.3 g AI/ha and against Anopheles quadrimaculatus were 0.09 and 0.1 g AI/ha. Cyfluthrin was about 106X more effective against An. quadrimaculatus and about 69X more effective against Ae. taeniorhynchus at the ED-95 level than malathion. PMID- 2906688 TI - Observations on male swarms of Psorophora columbiae in Texas ricelands. AB - The evening swarming behavior of newly emerged male Psorophora columbiae was studied in eastern Texas ricelands. Near infrared-sensitive video equipment was used to record swarming as it occurred in the field during each night of observation. Males of Ps. columbiae form either funnel-like or curtain-like marker swarms over a variety of objects in a riceland habitat. The sequence of events leading to swarm formation is described. Swarming males fly into the wind and follow a figure-8 pattern of flight. This flight pattern is modified by other insects flying through or near the swarm. Sudden changes in wind velocity or direction also modify the position and shape of the swarm relative to the marker over which it has formed. PMID- 2906689 TI - Species composition and relative abundance of anthropophilic mosquitoes in subarctic Quebec. PMID- 2906690 TI - Mosquitoes feeding on sheep in southeastern Wyoming. PMID- 2906691 TI - An efficient method for transferring adult mosquitoes during field tests. PMID- 2906692 TI - Absence of eastern equine encephalitis (EEE) virus in immature Coquillettidia perturbans associated with equine cases of EEE. PMID- 2906693 TI - Membrane and cytoplasmic structure at synaptic junctions in the mammalian central nervous system. AB - Application of rapid freezing, freeze substitution fixation, and freeze fracture techniques to the study of synaptic junctions in the mammalian central nervous system has revealed new aspects of synaptic structure that are consistent with and partially explicate advances in synaptic biochemistry and physiology. In the axoplasm adjacent to the presynaptic active zone, synaptic vesicles are linked to large spectrin-like filamentous proteins by shorter proteins that resemble synapsin I in morphology. This mesh of presynaptic filamentous proteins serves to concentrate synaptic vesicles in the vicinity of the active zone. The affinity with which the vesicles are bound by the mesh is probably modulated by the extent of phosphorylation at specific sites on the constituent filamentous proteins, and changes in the binding affinity result in changes in transmitter release. The structural organization of the postsynaptic density in Purkinje cell dendritic spines consists of very fine strands with adherent, heterogeneous globular proteins. Some of these globular proteins probably correspond to protein kinases and their substrates. The postsynaptic density, positioned at the site of the maximal depolarization caused by synaptic currents, apparently serves as a supporting framework for a variety of proteins, which respond to and transduce postsynaptic depolarization. At least two classes of filamentous protein fill the cytoplasm of spines with a complex mesh, which presumably contributes to maintenance of the spine shape. Membrane bound cisterns are a ubiquitous feature of Purkinje cell dendritic spines. Studies of rapidly frozen tissue with electron probe microanalysis and elemental imaging reveal that these cisterns take up and sequester calcium, which is derived from the extracellular space, and which probably enters the spine as part of the synaptic current. PMID- 2906694 TI - Alpha1-blockers with additional antihypertensive mechanisms. Satellite symposium of the 12th scientific meeting of the International Society of Hypertension. 28 May 1988, Kyoto, Japan. PMID- 2906695 TI - Clinical pharmacology of urapidil. AB - Animal investigations suggest that the mechanism of the antihypertensive effect of urapidil may be complex. Suggestions have included an alpha 1-blocking action, a weak beta 1-blocking effect, an interaction with a serotonin receptor and a central depression of sympathetic tone. Peripheral alpha 1-blocking activity has been demonstrated in man, and a shift to the right in the dose-response curve to phenylephrine has been found after administration of urapidil, while responses to angiotensin are not affected. Evidence for beta 1-blocking activity is marginal, but urapidil does not inhibit the exercise-induced increase in the heart rate, and there is only some suggestion of a possible inhibition of isoprenaline induced tachycardia. Possible central activity may be deduced from the observation that while lower single doses reduce blood pressure and increase the heart rate, with higher doses the hypotensive effect continues but the tachycardia no longer occurs. However, lower doses of urapidil lead to an increase in noradrenaline levels, while changes in renin are less constant, but there has been a report that a high dose reduced vanillylmandelic acid excretion. Urapidil reduces peripheral resistance along with arterial pressure, and cardiac output is increased. In spite of a reduced arterial pressure, renal blood flow is maintained, presumably due to dilation of renal vessels. Urapidil is well absorbed orally with a bioavailability of about 70% and a tmax at about 4 h after a sustained release capsule. It is metabolized in the liver with a t1/2 of 4.7 h. In conclusion there is evidence that urapidil is an alpha 1-blocking drug in man.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2906696 TI - Alpha-adrenoceptors and the kidney. AB - Sympathetic nerves may modify various aspects of renal function including renal haemodynamics, renin secretion and sodium output. In a series of experiments we found that within the human kidney alpha 2-adrenoceptors are of greater importance than alpha 1-receptors in mediating the adrenergic effects. For instance, intrarenal infusion of an alpha 1-antagonist has a small effect on renal perfusion, whereas blockade of alpha 2-receptors increases renal flow profoundly. There is evidence that the relevant receptors are located at a postjunctional site. Alpha 2-receptors also play an inhibitory role in renin secretion. Recent data suggest that the alpha 2-receptor, which reduces renin release, is located presynaptically. Thus, stimulation of this receptor reduces noradrenaline overflow, and hence diminishes beta-adrenoceptor mediated increases in renin. PMID- 2906697 TI - Systemic haemodynamic and humoral changes during urapidil treatment in hypertensive patients. AB - Urapidil, a new antihypertensive agent exerting a peripheral alpha 1-postsynaptic blocking action and an additional action at the central level, has some characteristics which may correct the underlying pathophysiological abnormalities found in the great majority of hypertensive patients. When administered acutely and chronically, urapidil significantly lowers blood pressure in hypertensive patients by reducing total peripheral resistance, while cardiac output is unchanged or only slightly elevated. The blood pressure reduction can cause a decrease in cardiac mass in patients with left ventricular hypertrophy. Urapidil has been successfully administered also in patients with congestive heart failure and in hypertensive crises during or following surgical procedures; in all these conditions urapidil lowers total peripheral resistance, but blood pressure is lowered only in patients with hypertensive crises and no clinically relevant reduction in blood pressure is found in patients with congestive heart failure. The acute administration of urapidil has shown a trend towards a rise in plasma renin activity, in plasma aldosterone and in plasma catecholamines; on the whole, however, the activation of these systems has been mild. PMID- 2906698 TI - Basic pharmacology of alpha-adrenoceptor antagonists and hybrid drugs. AB - Selective alpha 1-adrenoceptor antagonists, which can be used as antihypertensives, cause dilation of both resistance and capacitance vessels, as a result of alpha 1-adrenoceptor blockade at postsynaptic sites. Reflex tachycardia is weak or absent, owing to the following mechanisms: (1) The absence of presynaptic alpha 2-receptor blockade, thus preventing the accelerated release of noradrenaline from the nerve endings; and (2) the blockade of central alpha 1 adrenoceptors, causing a blunting of the reflex tachycardia via the baroreceptor mechanism. Prazosin and its successor drugs doxazosin, trimazosin and terazosin are the prototypes of selective alpha 1-adrenoceptor antagonists. Urapidil, labetalol and ketanserin are well-known examples of hybrid drugs, which possess additional pharmacological activities besides their alpha 1-adrenoceptor antagonistic potency. Labetalol is predominantly a (beta 1 + beta 2)-blocker with much weaker alpha 1-adrenoceptor antagonistic activity. The compound contains four stereoisomers with different pharmacodynamic properties and as such is not a true hybrid drug. Ketanserin is a selective 5-hydroxytryptamine (5HT2)-receptor antagonist, with modest alpha 1-adrenoceptor activity. Urapidil, a selective alpha 1-adrenoceptor antagonist, simultaneously displays central hypotensive activity which, unlike that of clonidine and related drugs, is not mediated by alpha 2-adrenoceptors. Urapidil is also a weak beta 1-blocker. It consists of one single molecule without stereoisomers and is therefore a true hybrid drug, combining two or more activities in the same molecule. Urapidil's obvious central hypotensive activity, which is caused by an unusual, so far unknown mechanism, is an interesting feature, which may contribute to the absence of reflex tachycardia. PMID- 2906699 TI - Urapidil in patients with severe hypertension and in long-term treatment. AB - In order to evaluate the usefulness of urapidil in the treatment of severe hypertension and in the long-term treatment of essential hypertension, two open multicentre studies were performed. In one study, 34 outpatients with diastolic blood pressure exceeding 105 mmHg following treatment with a combination of a diuretic and a sympatholytic or a diuretic and a beta-blocker were additionally given 15-60 mg urapidil twice a day for 8 weeks or more. The responder rate was 73.5%. The pulse rate did not change throughout. Side effects such as dizziness and malaise were observed in five patients (14.7%), but they were slight and did not require withdrawal of treatment. The other study included 95 outpatients with essential hypertension (World Health Organization stages I or II), 15-60 mg urapidil twice a day for 1 year or more in monotherapy (n = 48) or in combined therapy with a thiazide (n = 47). Under both therapies, diastolic blood pressure was reduced significantly at week 4, further reduced at week 12 and remained stable until week 52. Responder rates were 82.9% in monotherapy and 78.4% in combined therapy. Two patients (4.2%) taking monotherapy and six patients (12.8%) taking combined therapy were withdrawn due to inadequate blood pressure control or to side effects. These results indicate that urapidil is useful in severe and in long-term hypertension. PMID- 2906700 TI - The usefulness of alpha-adrenoceptor blockade in the treatment of hypertension. AB - The development of selective peripheral alpha 1-adrenoceptor antagonists such as prazosin has produced a valuable class of antihypertensive agents. Side effects of fluid retention and reflex sympathetic stimulation usually limit these agents to third-line therapy but their combination with a beta-receptor antagonist and a diuretic provides a powerful regimen. Alpha-adrenoceptor antagonists are useful in patients with conditions such as gout, diabetes or bronchospasm which preclude the use of other agents. Although many new drugs are being developed, little information is available yet on the long-term outcome of therapy with this class of drugs for patients with hypertension. PMID- 2906701 TI - Do hybrid drugs offer an additional benefit over pure alpha 1-blockade for hypertensive patients? AB - Alpha-blocking drugs, although effective antihypertensive agents, often cause tachycardia, faintness and postural hypotension. Hybrid drugs such as labetalol, which has beta- as well as alpha-blocking action, ketanserin, which has 5 hydroxytryptamine (5HT)-blocking as well as alpha-blocking action, and urapidil, which appears to have a central effect as well as an alpha-blocking action, produce fewer side effects attributable to alpha-blockade. Urapidil appears to be an effective antihypertensive drug with a wide spectrum of action and few side effects. PMID- 2906702 TI - Antihypertensive efficacy and safety of urapidil, alone or in combination with beta-blockers, in patients with phaeochromocytoma. AB - The clinical efficacy and safety of urapidil, used alone or in conjunction with beta-blockers, were evaluated in 14 patients with phaeochromocytoma. Following a 1-week placebo run-in period, the patients were treated with sustained-release capsules of urapidil, initially 30 mg twice a day, followed by dose adjustment within 30-270 mg (mean +/- s.d. 144 +/- 73) per day for 7-29 days (21 +/- 8 days). In six patients, beta-blockers were added to control associated tachycardia. Blood pressure and pulse rate were successfully controlled in 11/14 patients (78.6%) during the therapy. Both the frequency and the severity of hypertensive paroxysms were clearly reduced in 7/8 patients, who showed frequent paroxysms of hypertension during placebo treatment. A variety of subjective symptoms observed in 13 patients during placebo treatment improved during drug therapy in nine patients (69.2%). Side effects occurred in five patients but were minor and well tolerated except in one patient, who was withdrawn from urapidil monotherapy due to facial oedema and finger stiffness which persisted even after reducing the daily dose from 306 to 270 mg. Overall, in terms of antihypertensive effectiveness, improvement in subjective symptoms and the safety profile, urapidil was considered very useful in four patients (28.6%), useful in six (42.9%), slightly useful in three and useless in one. Urapidil therefore appears to be a worthwhile agent in the treatment of patients with phaeochromocytoma. PMID- 2906703 TI - Interaction of urapidil with brain serotonin-1A receptors increases the blood pressure reduction due to peripheral alpha-adrenoceptor inhibition. AB - The alpha-adrenoceptor antagonist urapidil influences central cardiovascular regulation, and this effect is unrelated to alpha-adrenoceptors. Since urapidil has appreciable affinity and selectivity for serotonin-1A (5HT1A) receptors, the activity of urapidil at these sites may be relevant for the centrally mediated component of its antihypertensive action. The latter hypothesis was tested by analysing the influence of the 5HT1A receptor antagonist spiroxatrine on the hypotensive response to urapidil, in comparison with the influence on the hypotensive response to the 5HT1A receptor agonist 8-OH-DPAT (8-hydroxy-2-[di-n propylamino]tetralin). Anaesthetized cats were thoracotomized and artificially ventilated. Blood pressure was monitored in the descending aorta, and the drugs were injected into the vertebral artery. Spiroxatrine (0.1-3.0 nmol/kg) shifted the cumulative dose response curve (blood pressure reduction) of urapidil (3-20 nmol/kg) and of 8-OH-DPAT (0.01-0.1 nmol/kg) to the right, suggesting competitive antagonism. The results support the hypothesis that the effects of urapidil on central cardiovascular regulation and at least part of the hypotensive effects are due to 5HT1A receptor stimulation. PMID- 2906705 TI - Ligament healing in podiatric surgery. PMID- 2906704 TI - Endoscopic laser Doppler flowmetry in evaluation of human gastric blood flow. PMID- 2906706 TI - Needle localization of foreign bodies using computed tomography. A case report. PMID- 2906707 TI - Clinical pharmacology of chronic atrial fibrillation. PMID- 2906708 TI - Ventricular beta-adrenoceptors in adriamycin-induced cardiomyopathy in the rabbit. AB - beta-Adrenoceptor concentrations have been measured in ventricles of rabbits with adriamycin-induced cardiomyopathy. Despite considerable cardiac hypertrophy (1.6 +/- 0.7 mean +/- S.E.M. g ventricle/kg body wt, n = 6; to 2.2 +/- 0.1) no change in beta-adrenoceptor density was observed (33.8 +/- 2.0 fmol/mg protein in membranes from cardiomyopathic rabbits compared with 36.8 +/- 3.0 for controls). Furthermore, no alteration in the profiles of high affinity agonist binding was observed, and the receptor interaction with the adenylate cyclase stimulatory coupling factor was unimpaired. These results indicate that, despite the marked changes which occur during the development of this model of low-output heart failure, the cardiac beta-adrenoceptor systems are normal. PMID- 2906709 TI - [Effects of a new alpha- and beta-adrenoceptor blocking drug (YM-09538) on intraoperative hypertension]. PMID- 2906710 TI - [A case of acute renal failure due to Korean hemorrhagic fever]. PMID- 2906711 TI - Microsurgery for male infertility. PMID- 2906712 TI - New directions in male reproductive microsurgery. AB - During the past decade, microsurgery has become a urologic subspecialty. Historically, vascular and vasal anastomosis have formed the foundation of genitourinary microsurgery. With the advent of improved instrumentation and the interest of devoted urologic microsurgeons, a multitude of new applications of microsurgery in urology have developed. In this paper, we discuss some of the new directions in male reproductive microsurgery. PMID- 2906714 TI - [Peptide and aminergic neurotransmitters in arterial hypertension]. PMID- 2906713 TI - [Molecular epidemiology of infective agents]. PMID- 2906715 TI - Plasma membrane ATPase from the yeast Schizosaccharomyces pombe. PMID- 2906716 TI - Plasma membrane ATPase from the yeast Saccharomyces cerevisiae. PMID- 2906717 TI - H+-ATPase from plasma membranes of Saccharomyces cerevisiae and Avena sativa roots: purification and reconstitution. PMID- 2906718 TI - Purification of yeast vacuolar membrane H+-ATPase and enzymological discrimination of three ATP-driven proton pumps in Saccharomyces cerevisiae. PMID- 2906719 TI - Purification of vacuolar membranes, mitochondria, and plasma membranes from Neurospora crassa and modes of discriminating among the different H+-ATPases. PMID- 2906720 TI - Large-scale purification of plasma membrane H+-ATPase from a cell wall-less mutant of Neurospora crassa. PMID- 2906721 TI - H+-ATPase from vacuolar membranes of higher plants. PMID- 2906722 TI - Preparation and acidification activity of lysosomes and lysosomal membranes. PMID- 2906723 TI - Analysis of endosome and lysosome acidification in vitro. PMID- 2906724 TI - Proton ATPases in Golgi vesicles and endoplasmic reticulum: characterization and reconstitution of proton pumping. PMID- 2906725 TI - Chromaffin granule proton pump. PMID- 2906726 TI - Proton pump of clathrin-coated vesicles. PMID- 2906727 TI - Purification of pertussis toxin. PMID- 2906728 TI - Assay of hemolytic toxins. PMID- 2906729 TI - Assay methods for alpha toxin from Clostridium perfringens: phospholipase C. PMID- 2906730 TI - Purification of alpha toxin from Clostridium perfringens: phospholipase C. PMID- 2906731 TI - Production, purification, and assay of Clostridium perfringens enterotoxin. PMID- 2906732 TI - Dual effects of histamine on spontaneous activity in isolated bovine mesenteric lymphatics. AB - The mode of action of histamine on spontaneous contractions is isolated bovine mesenteric lymphatics was investigated by recording isometric tensions. Histamine at lower concentrations between about 5 x 10(-8) and 10(-6) M caused a dose dependent deceleration of the rhythm of spontaneous contractions. Higher concentrations of histamine (more than about 5 x 10(-6) M) produced a dose related acceleration of the rhythm in association with a slight elevation of basal tone in 115 of 173 preparations. In 58 of 173 lymphatic preparations, histamine at concentrations ranging from about 5 x 10(-8) to 10(-5) M caused only the positive chronotropic effect. The histamine-induced positive and negative chronotropic effects were unaltered by pretreatment with alpha- and beta adrenergic antagonists but were dose-dependently antagonized by pretreatment with H1- or H2-blockers (diphenhydramine or cimetidine). The specific H1- and H2 agonists, 2-pyridylethylamine (2PEA) and dimaprit caused dose-related positive and negative chronotropic effects, respectively, on spontaneous contractions of isolated bovine mesenteric lymphatics. The effect of 2PEA was significantly blocked by pretreatment with 10(-6) M diphenhydramine, whereas the effect of dimaprit was suppressed by 10(-6) M cimetidine. These results suggest that both H1- and H2-receptors are located on the plasma membrane of smooth muscle cells in bovine mesenteric lymphatics, and that the excitations of H1- and H2-receptors respectively produce an acceleration and a deceleration of the rhythm of spontaneous contractions in lymphatic smooth muscles. PMID- 2906733 TI - [The effect of ground water table levels on mosquitoes from the Hungry steppe in the Uzbeck SSR]. PMID- 2906734 TI - [The number of blood-sucking mosquito larvae in technogenous bodies of water in the Taimyr forest tundra]. PMID- 2906735 TI - [Mass breeding of Culex pipiens molestus Fors. mosquitos and their attack on humans in houses in several towns in the Krasnoiarsk region and Chita district]. PMID- 2906736 TI - Hepatic microvascular regulatory mechanisms. X. Effects of alpha-one or -two adrenoceptor blockade on glucoregulation in normotensive endotoxic rats with optimal perfusion and flowrates. AB - Circulating-blood glucose, hepatic glycogen distribution, and the glycogen contents of liver and skeletal muscle, were determined for 60 min in 31 fed and anesthetized Sprague-Dawley rats. These rats received an endoportal infusion of 15 mg per kg b.w. E. coli endotoxin (026:B6) or of sterile saline solution as a control. Either substance was given intravenously at 9:30 a.m. following an intraperitoneal injection at 9:00 a.m. of 0.1 mg per kg b.w. prazosin or 0.3 mg per kg b.w. yohimbine or of the carrier, distilled water. Infused endotoxin elevated blood glucose without affecting hepatic glycogen distribution and total glycogen contents of liver and skeletal muscle when compared to control. Prazosin inhibited endotoxin-induced hyperglycemia, and prazosin plus endotoxin provoked centrilobular glycogen depletion and decreased total hepatic glycogen content. However, no significant alteration in the glycogen content of skeletal muscle accompanied blockade of glucogenesis. Prazosin administered by itself produced no changes in hepatic and muscle glycogen. Although yohimbine blocked endotoxin induced hyperglycemia, yohimbine, or yohimbine plus endotoxin, produced no significant change in the glycogen contents of liver and skeletal muscle. Blockade in the latter case was associated with some depletion of glycogen in hepatocytes dispersed randomly throughout the unit lobule and in cells located centrivenously. These results suggested that endotoxin-induced hyperglycemia is evoked by activation of alpha-1 and -2 adrenergic receptors. Since no detectible change in hepatic glycogen distribution and in the contents of liver and muscle glycogen accompanied glucogenesis, glycogen catabolism and deposition are postulated to proceed simultaneously and at equivalent rates by 60 min following the experimental induction of endotoxemia. Blockade of alpha (one or two) adrenoceptors is hypothesized to inhibit endotoxin-induced hyperglycemia by facilitating glucose utilization and not by stimulating glycogenesis or by antagonizing glycogenolysis in the liver or skeletal muscle. PMID- 2906738 TI - [Galvanic corrosion of dental Ni-Cr alloy by contact with dental solders. Part 3. Observation of soldered joints]. PMID- 2906737 TI - Comparison of the effects of dopamine and fenoldopam, a selective dopamine-1 agonist, on parathyroid hormone release in man. AB - Dopamine has been reported to transiently increase parathyroid hormone (PTH) secretion in man; however, the mechanism is unclear. To test the hypothesis that selective dopamine-1 receptor (DA1) stimulation increases PTH secretion, we compared the effects of fenoldopam, a novel selective DA1 receptor agonist, as well as dopamine on serum PTH secretion and total serum calcium concentration in seven normal human subjects. Dopamine was infused at 1 and 3 micrograms/kg/min, each for 10 minutes, and 5 micrograms/kg/min for 25 min. Fenoldopam was infused at 0.1 and 0.3 micrograms/kg/min, each for 10 min. and thereafter at 0.5 micrograms/kg/min for 25 min. The infusions were given at least 1 week apart. Blood samples for PTH, calcium and dopamine or fenoldopam concentrations were drawn prior to and at the 25th minute of each drug infusion. PTH concentrations increased in all subjects at the 25th minute of dopamine but not fenoldopam infusion. Serum calcium was not significantly affected. The plasma concentrations of both dopamine (83.6 +/- 7.1 ng/ml) and fenoldopam (13.0 +/- 3.4 ng/ml) were in the range known to cause equivalent DA1 receptor stimulation. Since dopamine but not fenoldopam increased PTH secretion in man, we conclude that selective DA1 receptor stimulation alone does not increase PTH release and the effects of dopamine must be mediated through some other mechanism. PMID- 2906739 TI - Brain chemistry and central nervous system drugs. PMID- 2906740 TI - Neurotransmitter systems in the outer plexiform layer of mammalian retina. AB - Melatonin represents a second type of chemical signal released from photoreceptors in response to increased darkness, one with characteristics which are significantly different from those of glutamate. Concise spatial and temporal aspects of the photoreceptor signal are conserved through discrete glutamatergic synapses. Different classes of post-synaptic neurons each have appropriate subclasses of glutamate receptors which transmit sign conserving or sign inverting images of the visual mosaic. In contrast, melatonin, because of its highly lipophilic nature is not released by stimulus-coupled secretion mechanisms, but rather by simple diffusion. Thus control of melatonin "release" may be less concise than glutamate. In addition, melatonin may diffuse beyond the confines of the synaptic area to target cells throughout the retina. Effects of melatonin in retina are not well understood; however, current hypotheses suggest that, perhaps via its control of dopamine systems in the inner retina, melatonin plays an important role in dark adaptation and in various retinal processes which exhibit a circadian rhythm. Melatonin and glutamate may represent "co transmitters" which provide the visual pathway with two types of signals, with melatonin providing widespread modulatory influences on the discrete visual information conveyed via glutamatergic circuits. PMID- 2906741 TI - Does noradrenaline behave as a neurotransmitter or hormone in the mammalian retina? PMID- 2906742 TI - Differences in glutamate-induced response properties between photoreceptors and horizontal cells. PMID- 2906743 TI - Localization of the X-linked retinitis pigmentosa locus between DXS7 and DXS84 in a family showing tapetal reflex in heterozygotes. AB - The linkage relationships between the X-linked retinitis pigmentosa (XLRP) locus and seven Xp loci: DXS14, DXS7, OTC, DXS141, DXS148, DXS84 and DXS206 were analysed in one large family in which the heterozygotes exhibited the tapetal reflex. Evidence drawn from two-point and multipoint linkage analysis and a number of triply informative crossovers suggests that the XLRP locus in this family is between DXS7 and DXS84. The putative order of loci on the short arm of the X chromosome is: centromere - DXS14 - DXS7 - OTC - XLRP/DXS141 - DXS148 - DXS84 - DXS206 - telemere. PMID- 2906744 TI - Intraocular pressure effects of timolol after unilateral instillation. AB - Beta-adrenergic antagonists are generally considered to lower intraocular pressure (IOP) of both eyes after unilateral instillation. In order to determine whether timolol also lowers IOP in the contralateral eye and to what extent, pressure curves were established in 14 normal, young subjects. Eye pressure curves on both eyes of each subject were measured before and 1 week after timolol 0.5% instillation twice daily in one eye. All subjects had an IOP decrease in the treated eye, but no subjects had a statistically significant IOP decrease in the contralateral eye. The mean IOP reduction was 26% in the treated eye, and only 3% in the contralateral eye. These results suggest that, in most cases, timolol does not lower IOP in the contralateral eye after unilateral instillation in normal subjects in contrast to certain glaucoma patients. These results suggest two different actions for timolol: (1) a local action in the treated eye, and (2) a systemic action where the pressure-lowering effect in the untreated eye is significant only in some pathologic conditions. PMID- 2906745 TI - [Treatment of hemoptysis and hemorrhage using pyrilen and temechin in patients with pulmonary tuberculosis]. PMID- 2906746 TI - [Pulmonary vasculitis in a patient with periarteritis nodosa]. PMID- 2906747 TI - Amacrine cells in the retina of a teleost fish, the roach (Rutilus rutilus): a Golgi study on differentiation and layering. PMID- 2906748 TI - Behavioural effects of the alpha 2-adrenoceptor antagonists idazoxan and yohimbine in rats: comparisons with amphetamine. AB - Although yohimbine has long been known to increase arousal, reactivity and anxiety in animals and humans, little is known about the behavioural effects of more selective alpha 2-adrenoceptor antagonists such as idazoxan. In a recent experiment, however, it was found that in rats both yohimbine and idazoxan increased low rates of lever pressing, an effect also produced by amphetamine. The purpose of the present study was to investigate further the effects of yohimbine and idazoxan in comparison with those of d-amphetamine on the operant behaviour of rats. In rats trained to press a lever on a FI 60s schedule to obtain food both yohimbine and idazoxan increased response rates, although the effect of yohimbine was considerably greater than that of idazoxan. Lower doses of d-amphetamine had no consistent effect on overall rates of responding whereas a higher dose suppressed responding. Characteristically, d-amphetamine increased responding during early portions of the intervals and decreased responding during the final portions. Idazoxan and yohimbine tended to increase responding throughout the intervals except immediately after reinforcement. When idazoxan was administered in combination with prazosin FI response rates were markedly decreased. Administration of DSP4 did not alter the response rate-increasing effects of either yohimbine or idazoxan. In rats trained to discriminate d amphetamine from saline both idazoxan and yohimbine gave rise to responding on the saline associated lever. Combination of idazoxan with d-amphetamine did not antagonise the amphetamine cue but produced substantial reductions in response rates, probably due to toxicity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2906750 TI - Effect of vasopressin on the induction of adrenal tyrosine hydroxylase and phenylethanolamine N-methyltransferase. AB - We have assessed the effect of arginine vasopressin (AVP) on adrenal tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT) activities. Both enzymes show marked increases after systemic administration of AVP in the range of 66 and 100 micrograms/day. To determine whether the pituitary gland plays a role in these inductions, the effect of AVP (66 micrograms per day, given divided into 3 doses for 4 days) on the adrenal enzymes was studied in hypophysectomized rats. These animals showed induction of TH but not PNMT. This indicates that a pituitary factor(s) mediates the increase in PNMT caused by AVP. Adrenal TH activity was measured after the injection of AVP (1 or 2 micrograms per rat) into the lateral ventricle: there was a statistically significant increase in TH. TH was not induced in the denervated adrenal gland of rats administered AVP systemically. These findings suggest that AVP may act centrally to induce the enzyme. The continuous s.c. infusion of AVP by osmotic minipump at the rate of 1 microgram/day for 6 days led to a striking increase in adrenal TH activity. However, PNMT did not increase significantly. It can be concluded that different mechanisms are involved in the induction of adrenal TH and PNMT caused by AVP. A neural mechanism is involved in TH induction, whereas PNMT induction requires release of a pituitary factor, presumably ACTH, but innervation of the adrenal is not needed for it. Moreover, the inductions of these two enzymes are differentially sensitive to the concentration of circulating AVP. PMID- 2906749 TI - Chronic neuroleptics alter the effects of the D1 agonist SK&F 38393 and the D2 agonist LY171555 on oral movements in rats. AB - Vacuous oral movements (OMs) in rats chronically administered haloperidol (HAL), fluphenazine (FLU), or no drug were studied following injections of one of three doses of either a D1 agonist (SK&F 38393) or a D2 agonist (LY171555). Oral movements were observed via closed-circuit television and simultaneously recorded using a computerized video analysis system which measured the distance between two fluorescent dots painted above and below the rat's mouth. SK&F 38393 induced a dose-dependent increase in tremorous oral movements and repetitive chewing movements in the controls; this effect was more pronounced in rats treated with chronic HAL or FLU, both during chronic neuroleptic treatment and even more so when they were tested after drug withdrawal following 5 or 14 months of chronic neuroleptic administration. Conversely, LY171555 produced an inhibition of oral activity at all dose levels in controls. This inhibition was attenuated during chronic administration of HAL or FLU, but returned to control levels (without any signs of supersensitivity) when the animals were retested shortly after discontinuation of neuroleptics. These results indicate that heightened oral movements in rodents following chronic neuroleptic administration can be more clearly induced by D1 than by D2 receptor activation. PMID- 2906751 TI - [Somatostatin does not modify 3-oxymethylglucose and leucine uptake by rat enterocytes]. AB - The effects of somatostatin on 3-oxymethylglucose (3-OMG) and leucine uptake by rat enterocytes were examined. Somatostatin did not decrease the 3-OMG enterocyte uptake. When the 3-OMG active transport was inhibited by phloridzin, Somatostatin presented no significant modifications. Somatostatin showed a slight decrease in 3-OMG release through the basolateral membrane, when such a release was inhibited with theophylline. Somatostatin did not modify the intestinal leucine uptake or its inhibition by methionine. PMID- 2906752 TI - [Chemical neuroanatomy of the human spinal cord]. AB - Modern neuroanatomical methods, specifically immunocytochemistry and receptor autoradiography, have greatly increased our knowledge on the organization of the human nervous system. This review, based on the literature and largely on personal results, is devoted to the chemical neuroanatomy of the normal human spinal cord. It provides a comprehensive overview of the differential distribution of various chemical messengers, their metabolizing enzymes and their receptors (acetylcholine, amino acids, monoamines, neuropeptides) in the neuronal laminae of the spinal gray matter. At the level of the dorsal horn, lamina II, i.e. Rolando's substantia gelatinosa, is characterized by a heavy concentration of several transmitters and receptors. Within the intermediate gray matter the autonomic nuclei receive a dense peptidergic input, e.g. substance P, enkephalin and VIP afferents. In the ventral horn close contacts are numerous between serotonergic or peptidergic (SP, TRH, enkephalins...) fibers and motoneuronal perikarya or dendrites. The present knowledge on the putative role of certain neurotransmitters in spinal functions is summarized. PMID- 2906753 TI - [Subarachnoid hemorrhage as initial manifestation of polyarteritis nodosa]. AB - The polyarteritis nodosa (P.A.N.) is frequently responsible of neurological disorders, both central and peripheral. However an involvement of the Central Nervous System is unusual at the beginning of the disease. Such particular case is reported having occurred in a man aged 49, struck by a subarachnoidal hemorrhage, which was an initial symptom of P.A.N. The differential diagnosis is not always easy in such cases, since the clinical findings could be mistaken for those of a subarachnoidal hemorrhage due to a malformed vessel rupture. PMID- 2906754 TI - [Neurotransmitters and cerebral aging]. PMID- 2906755 TI - [Isolation, stress and neurotransmitters]. PMID- 2906756 TI - [The value of a pursuit in the long run]. PMID- 2906757 TI - [Neurobiological deficit in individuals over 50 years of age. From physiopathology to therapy]. PMID- 2906758 TI - Phenotypical and functional characterization of the idiotype-positive blood B cells in multiple myeloma. AB - In this study the idiotype-positive B cells of one patient with smouldering multiple myeloma (IgG kappa) and of one patient with multiple myeloma (IgG lambda) were analysed phenotypically and functionally. As regards the expression of B cell-associated differentiation antigens and size distribution, the idiotype positive B cells resembled normal IgG-bearing blood B cells. In functional studies the lymphocytes were cultured in vitro with Staphylococcus aureus, pokeweed mitogen, T-cell factors, or combinations of these. After culture, proliferation and differentiation of the idiotype-positive B cells were measured by autoradiography, an idiotype-specific ELISA, and a spot ELISA. The results show that idiotype-positive B cells of both patients are able to proliferate after stimulation in vitro. In contrast to their normal counterparts, however, almost no increase in the amount of secreted idiotype IgG could be induced. This suggests that the idiotype-positive blood B cells have lost some of their ability to respond to exogenous stimuli. PMID- 2906759 TI - [Orthopedic technic in sports injuries of the hindfoot]. PMID- 2906760 TI - Sulfasalazine in the rheumatic disease. PMID- 2906761 TI - Approach to hepatic involvement by endocrine tumors of the gastrointestinal tract. AB - Endocrine cells of the GI tract derive from stem cells of the neurocrest. They belong to the diffuse endocrine system as defined by Feyrter and share common features, such as the capacity for APUD cells. From these regulatory peptide producing cells, endocrine tumors may develop with specific clinical symptoms. In some other endocrine GI tumors, no hormone secretion has yet been found, and for some regulatory peptides, no specific clinical entity has yet been identified. Diagnosis can be confirmed by hormone measurements and by specific immunohistochemistry or electron microscopy of the tumor tissue. Metastases synthesize and secrete peptide hormones like those of the primary tumors. The principal target organ for metastases is the liver. Several approaches to treatment of hepatic tumor deposits may reduce tumor mass with consequent reduction of effective plasma hormone levels. There are also systemic treatments for neuroendocrine tumors from the GEP system. PMID- 2906763 TI - Rx for a healthier practice: professional medical assistants. PMID- 2906762 TI - [The Russian Social-Democratic Labor Party fights against alcohol drinking and alcoholism]. PMID- 2906764 TI - Effects of hormonal contraceptives on breast milk composition and infant growth. World Health Organization (WHO) Task Force on Oral Contraceptives. AB - Breast milk volume and composition and infant growth were measured at three- and four-week intervals, up to six months, in a multicenter randomized double-blind trial comparing a low-dose combined oral contraceptive (OC) with a progestogen only OC. A nonrandom group using nonhormonal methods was also studied in the three centers: Szeged, Hungary; Bangkok, Thailand; and Khon Kaen, Thailand. A fourth group, users of depot-medroxyprogesterone acetate (DMPA) was included in the two Thai centers. Altogether, 341 women were recruited into the study. Combined OCs caused a significant decrease in milk output and total energy content as well as widespread changes in milk constituents. In the DMPA group, no significant changes were observed in milk volume, and only minor shifts occurred in milk composition, which varied between centers. No differences were found between the progestogen-only pill and DMPA. No hormonal contraceptive was associated with any significant difference in infant weight or fat fold, nor in the rate of discontinuation for failure to gain weight. This study reiterates the need to avoid combined OCs during the first few weeks or months of lactation. Both norgestrel and DMPA appear to be safe for use in both developing and developed countries, at least when the nutritional status of the mother and infant are adequate, but further research is needed on the safety of these contraceptives in populations with malnutrition. PMID- 2906765 TI - Role of beta-glucuronidase, a lysosomal enzyme, in the pathogenesis of intestinal amoebiasis: an experimental study. AB - The role of beta-glucuronidase (BG), released by blood monocytes and Kupffer cells, in the pathogenesis of intestinal amoebiasis was studied. Guinea-pigs, infected intracaecally with Entamoeba histolytica, were killed 0, 3, 7, 14 and 21 d after infection. Enhanced levels of BG were observed in the cell lysates as well as supernatants of both blood monocytes and Kupffer cells in the infected animals, from the 3rd day after infection, as compared to those in controls. The rise in BG levels was more marked on 7 and 14 d after infection (P less than 0.001). The animal which survived for 21 d had lower levels of BG, though still significantly higher than those in controls (P less than 0.05). The animals with grade IV or V caecal scoring and on the verge of death had higher levels of beta glucuronidase. A direct correlation was observed between the enzyme levels and severity of infection. It is postulated that acid hydrolases have a role in causing tissue damage during intestinal amoebiasis. PMID- 2906766 TI - Abdominal vein distension in amoebic liver abscess. PMID- 2906767 TI - Distribution of pathogenic zymodemes of Entamoeba histolytica. PMID- 2906768 TI - A high rate of neurological complications following Semple anti-rabies vaccine. AB - A fatal case of encephalitis due to Semple (phenolized sheep-brain) anti-rabies vaccine prompted a search for neurological complications among 722 recipients of 2 vaccine batches administered in Bangkok, Thailand in June and July 1984. A review of all patients admitted with neurological symptoms from June through August 1984 to the 5 major teaching hospitals in Bangkok found 6 cases (0.83%), including the index case, who had received the vaccine. Rabies infection was ruled out in all 6 cases. 4 patients had meningitis, and 2 had meningo encephalitis. Only the index case was fatal; the other patients recovered without neurological sequelae. The rate of neurological complications after receiving Semple vaccine was therefore a minimum of 8.31 cases per 1000 persons vaccinated (1:120). This complication rate was about 25 times higher than the overall complication rate of 0.33 per 1000 (1:3018) determined from 14 previous reports. The fatality rate was 1.39 per 1000 (1:722), about 15 times higher than the rate of 0.09 per 1000 (1:10805) calculated from the previous studies. It is urgent to find economically feasible alternatives to Semple vaccine. PMID- 2906769 TI - [Experiences with a total implantable system for the epidural administration of opiates]. PMID- 2906770 TI - Studies on the antigenic relationships of six adherent isolates of Bordetella bronchiseptica. AB - Six isolates of Bordetella bronchiseptica recovered from swine with atrophic rhinitis were studied. All hemagglutinated swine red blood cells, autoagglutinated in saline and showed fimbriae by electron microscopy. Hyperimmune sera against each were produced in rabbits and the antigenic relationships between the isolates were studied by cross-absorption and by the determination of the cross-reactivity indices of pairs of sera. Three isolates seemed to be identical by both methods, while 2 others showed close antigenic relationships. Hemagglutination titers with heterologous antigens and cross reactivity indices greater than 0 suggest some degree of cross-immunity among the isolates studied, even when antigenic heterogeneity was demonstrated. PMID- 2906771 TI - A modified parainguinal approach for cryptorchidectomy in horses. An evaluation in 107 horses. AB - A modified parainguinal approach was used to castrate 119 abdominal cryptorchid horses. The operative time ranged from 10 to 30 minutes. Follow-up information was obtained for 107 horses. Swelling, more severe than that expected in routine castrations, was reported in six horses. An incisional abscess had to be drained in one horse and one horse died of unexplained causes 3 days after the surgery. PMID- 2906772 TI - [On the pathogenesis of migraine]. PMID- 2906773 TI - [Changes in the reference system exemplified by a visual assessment task]. PMID- 2906774 TI - [Programming of structural properties of movement sequences]. PMID- 2906775 TI - Factor structure of the Hamilton Rating Scale for Depression among depressed elderly Finns. PMID- 2906776 TI - [Psychosynergetics--new perspectives for neuropsychology? Principles of the psychosynergetic theory of emotional and motivational processes]. PMID- 2906777 TI - Do ranitidine and nizatidine influence pepsin secretion? PMID- 2906778 TI - A new lormetazepam galenical formulation for sublingual premedication. AB - This study reports a double-blind evaluation of a new formulation of lormetazepam for sublingual administration, given as a premedicant in 48 female patients undergoing minor gynecological procedures. Both patient's and nurse's assessments for anxiety and sedation were recorded at different times. Anxiolysis and sedation were present 30 minutes after administration of the drug as reported by the patient with a peak effect at 45 minutes. Nurses reported significant differences in sedation only, but already present at 30 minutes after premedication. The memory test showed no persistent effect of the benzodiazepine one day after surgery. PMID- 2906779 TI - Effects of maternal phenylalanine or tyrosine hydroxylase inhibition on postnatal maturation of catecholamine and amino acid metabolism in rats. PMID- 2906780 TI - Neuroleptic medication facilitates the natural occurrence of tardive dyskinesia. A critical review. AB - The literature concerning the connection between Tardive Dyskinesia (TD) and the chronic use of neuroleptics is reviewed. On the average, three times more TD's can be observed in a population treated chronically with neuroleptics (about 20%) than in untreated groups (5-9%). Various analyses do not justify the contention that one neuroleptic or group of neuroleptics would elicit more TD's than another one. Questions about the mechanisms by which TD is brought about remain unanswered. More attention is now being paid to brain function and age. Possible changes in the sensitivity of the dopamine receptor are no longer being regarded as a primary mechanism. A working hypothesis is proposed according to which TD would be induced by various adaptation mechanisms in the brain, which also points to a possible explanation of the reversibility of TD. It is now accepted that TD symptoms can disappear or improve greatly in about 60% of patients during the course of 2-3 years, which reduces the group of irreversible TD's to the number of spontaneously occurring dyskinesias. PMID- 2906781 TI - Diagnostic work-up of hyperprolactinemic disorders. AB - Substantial advances have been made in the understanding of chronic hyperprolactinemia. The diagnostic effort should be directed at excluding physiological and pharmacological causes of chronic hyperprolactinemia, both of which are reversible and are not likely to be of grave consequence. Subsequently further efforts should be made to rule out obvious pathological entities, in particular, treatable hypothyroidism. Finally, the diagnosis of prolactinoma must be entertained. It relies on the biochemical determination of prolactin as well as direct imaging of the pituitary. PMID- 2906782 TI - Molecular structure, biology, and genetics of prions. PMID- 2906783 TI - Prophylaxis against acid aspiration syndrome. Single oral dose of H2-antagonist on the evening before elective surgery. AB - We have compared famotidine 40 mg, ranitidine 300 mg and placebo given in a single oral dose at 2200 hours as the sole means of prophylaxis in 286 patients who underwent elective surgery the following day. Standardised premedication was administered and anaesthesia induced. Gastric contents were aspirated by nasogastric suction and the pH and volume measured. Median values of pH after famotidine, ranitidine and placebo were 6.17, 6.74 and 2.45 respectively; median aspirate volumes were 8, 8 and 10 ml respectively. The proportions of patients considered 'not at risk' (pH greater than 2.5) were 90% after famotidine, 91% after ranitidine and 52% after placebo. We conclude that the administration of a potent H2-antagonist in a single oral dose at night offers a convenient routine means of providing extensive prophylactic cover in patients scheduled to undergo elective surgery the following day. PMID- 2906784 TI - The scientific basis of patient-controlled analgesia. AB - The current practice of patient-controlled analgesia has grown from empirical observations. Although several variants of patient-controlled analgesia, bolus doses, infusions, or combinations of both, have been suggested, a scientific basis for advocating one variant over the others has been lacking. Most systems have been based on the simplest system, bolus demand, although the use of a combined bolus and background infusion method has theoretical merit. Similarly, a scientific basis for setting the variables of patient-controlled analgesia, drug choice, incremental dose, maximum dose and lockout interval, also has been lacking. Settings for these variables may be rationalised post hoc on the basis of the physicochemical properties and global pharmacokinetic properties of the opioids used but knowledge of these properties has not helped in setting the variables a priori. Foremost, the drug choice should be based on therapeutic index. Knowledge of the regional kinetics of drug (influx and efflux) from brain may provide a more logical basis for setting the patient-controlled analgesia variables but such information can only come from animal experiments. More research is required if patient-controlled analgesia is to become anything but an empirical tool in the quest for improved analgesia in patients. PMID- 2906785 TI - The development and clinical use of patient-controlled analgesia. AB - Patient-controlled analgesia has successfully made the transition from research tool to clinical acceptability. Reliable and sophisticated patient-controlled analgesia systems are commercially available. The technique has been most used for control of postoperative pain but has been successfully used during labour, after burns and other trauma and in terminal care. Virtually every opioid has been administered by patient-controlled analgesia using almost every route of administration. It is more effective than the traditional techniques of pain control after surgery but is not automatically so. Choice of opioid and the settings chosen for demand dose and lockout interval greatly influence effectiveness. Patient-controlled analgesia requires active participation by the patient but the psychology of patient-controlled analgesia has generally been under-estimated. Patient-controlled analgesia has developed empirically and many assumptions have been made; there is a need for fundamental research. PMID- 2906786 TI - Education in anaesthesia in Australia: a centenary. AB - This year marks the centenary of the beginning of teaching in anaesthesia in Australia. Until 1888 there were no appointments in anaesthesia at any hospital, but in that year two were made. A brief review of the events leading to this change is given, with an even briefer review of the main steps in the transformation of education in anaesthesia in Australia on which the present-day system is based. PMID- 2906787 TI - Spectrophotometric determination of some phenothiazine drugs using 3 methylbenzothiazolin-2-one hydrazone. PMID- 2906788 TI - Somatostatin-14-like immunoreactive neurons and fibres in the human olfactory bulb. AB - This study describes the morphological features and the distribution pattern of neurons in the human olfactory bulb which are immunoreactive for an antiserum against the neuropeptide somatostatin-14. Immunoreactive nerve cell bodies were mainly found in the white matter surrounding the cell clusters of the anterior olfactory nucleus. Some immunoreactive neurons were also found scattered throughout the anterior olfactory nucleus and the deeper parts of the inner granule cell layer. Only a few immunoreactive neurons were localized in the glomerular layer and the outer granule cell layer. Immunoreactive fibres were found in all layers of the olfactory bulb. In addition, an impressive number of coiled and kinked immunoreactive fibres were localized within the anterior olfactory nucleus forming a dense plexus. Accumulations of twisted and coiled branches of immunoreactive fibres were rarely found either surrounding or within the olfactory glomerula. The characteristics of somatostatin-14 immunoreactive neurons as seen in the combined pigment-Nissl preparation were studied after decolourizing the chromogen and restaining the preparations with aldehydefuchsin in order to demonstrate the lipofuscin pigment and gallocyanin chrome alum for Nissl material. About 90% of the immunoreactive neurons studied in this manner turned out to be devoid of lipofuscin granules. The remaining 10% displayed different patterns of pigmentation. These findings suggest the presence of different types of somatostatin-14-like immunoreactive neurons in the olfactory bulb of the human adult. PMID- 2906789 TI - Restriction fragment length polymorphisms of horse class II MHC genes observed using various human alpha- and beta-chain cDNA probes. AB - Genomic DNA isolated from 20 horses was digested with up to six restriction endonucleases and subjected to southern blot hybridization analysis using various human class II alpha- and beta-chain cDNA probes. A high degree of restriction fragment length polymorphism (RFLP) was found for the DQ alpha, DP beta, DQ beta and DR beta probes, about 20 polymorphic bands being detected for each. DR alpha showed 2-4 polymorphic bands, whereas no evidence for DP alpha-like genes was found. A number of correlations of RFLPs with individual alloantisera were apparent. PMID- 2906790 TI - Equine disease association studies: a clinician's perspective. AB - Diagnostic criteria should be carefully defined and described in disease association studies to allow (1) comparison among studies from different laboratories evaluating the same disease, (2) critical evaluation of selection procedures of patients, and (3) to strengthen genuine associations with any genetic marker system. Factors to consider include age at onset of disease, specialized diagnostic methods necessary to diagnose or eliminate patients with a selected disease, ranges of affectedness and differences in sex expression. PMID- 2906791 TI - Association of arytenoid chondritis with equine lymphocyte antigens but no association with laryngeal hemiplegia, umbilical hernias and cryptorchidism. AB - Associations were sought between ELA A1-A10 and W11 antigens and the presence of laryngeal hemiplegia, arytenoid chondritis, umbilical hernias and cryptorchidism in Thoroughbreds and/or Quarter Horses. No significant associations were detected between laryngeal hemiplegia and any ELA antigen in Thoroughbreds. The association between arytenoid chondritis and A9 was significant with a relative risk (RR) of 15.6 and aetiologic fraction (EF) of 0.80 in Thoroughbreds. There were apparent associations based on RR between A4 and A5 in Quarter Horses with umbilical hernias (RR = 7.5 and 6.1 respectively); however, these were not statistically significant. No significant associations were detected with cryptorchidism in Quarter Horses when the control population included both sexes. When only unaffected males were used as the control group, there was an apparent increase in relative risk with A6 (from RR = 1.7 to 4.3); however this was not statistically significant. Cryptorchidism in Thoroughbreds showed an increased relative risk with A5 regardless of whether the control population included males and females (RR = 4.1) or only males (RR = 4.7) but the increases were not statistically significant. PMID- 2906792 TI - [The concept of "genetic marker" (old wine in new wineskins)]. PMID- 2906793 TI - Closure of a sternal defect with the rectus abdominis muscle after sacrifice of both internal mammary arteries. AB - Infections of the median sternotomy incision are relatively uncommon. Successful treatment of this serious complication consists of adequate surgical debridement and obliteration of mediastinal dead space using the pectoralis major muscle, or the rectus abdominis muscle or both. The recent use of internal mammary artery grafts has created a new problem in closure of defects involving the lower one third of the sternum. Under these circumstances the use of the rectus abdominis muscle is believed to be contraindicated. To date omental transposition remains the only alternative in therapy. A case of sternal dehiscence after coronary artery bypass surgery is described. Bilateral internal mammary artery grafts were used. A rectus abdominis flap based primarily on the eighth anterior intercostal perforator was transposed into the defect. The wound healed uneventfully after initial loss of a 3-cm portion of the skin graft. Success of this flap based on intercostal perforators is postulated to be secondary to a "delay" phenomenon related to prior division of the dominant blood supply. PMID- 2906794 TI - Purification and characterisation of glutamine synthetase from Nocardia corallina. AB - Glutamine synthetase (GS) (EC 6.3.1.2) has been purified 67-fold from Nocardia corallina. The apparent Mr of the GS subunit was approximately 56,000. Assuming the enzyme is a typical dodecamer this indicates a particle mass for the undissociated enzyme of 672,000. The GS is regulated by adenylylation and deadenylylation, and subject to feedback inhibition by alanine and glycine. The pH profiles assayed by the gamma-glutamyl transferase method were similar for NH+4-treated and untreated cell extracts and an isoactivity point was not obtained from these curves. GS activity was repressed by (NH4)2SO4 and glutamate. Cells grown in the presence of glutamine, alanine, proline and histidine had enhanced levels of GS activity. The GS of N. corallina cross-reacted with antisera prepared against GS from a Gram-negative Thiobacillus ferrooxidans strain but not with antisera raised against GS from a Gram-positive Clostridium acetobutylicum strain. PMID- 2906795 TI - [Fertility in surgically treated patients for bilateral undescended testes]. PMID- 2906796 TI - Cytoprotective action of roxatidine acetate HCl. AB - The cytoprotective action of roxatidine acetate HCl (roxatidine) was investigated. We also studied the involvement of endogenous prostaglandins (PGs) in the cytoprotective action of roxatidine and the effect of roxatidine on SRS content in pleurisy induced by A23187. Simultaneously, these effects of roxatidine were compared with those of other histamine H2-receptor antagonists at the same anti-secretory activity level. Roxatidine prevented formation of the gastric mucosal lesions induced by abs. ethanol, 0.6 N HCl and 0.2 N NaOH, but it failed to prevent 30% NaCl-induced gastric mucosal lesions. Cimetidine, ranitidine and famotidine failed to prevent formation of the gastric mucosal lesions induced by necrotizing agents. The cytoprotective action of roxatidine was not abolished by pretreatment with indomethacin. Roxatidine did not greatly influence SRS production. Consequently, it appears that roxatidine has a cytoprotective action and that this action is not associated with endogenous PGs and SRS. PMID- 2906797 TI - Effect of ergolines on neurotransmitter systems in the rat brain. AB - The interaction of nicergoline with various monoaminergic receptors and its effects on monoamine turnover were studied in specific rat brain areas in comparison with those of its metabolites, 10-methoxy-1,6-dimethyl-ergoline-8 beta methanol (MMDL) and 10-methoxy-6-methyl-ergoline-8 beta-methanol (MDL). Nicergoline showed marked in vitro affinity for alpha 1-noradrenergic receptors (IC50 = 0.2 nM), less for alpha 2, S1 and S2 (IC50 about 10(-7) M). Its strong interaction with alpha 1-receptors was confirmed in vivo. The affinity of the other ergolines for alpha 1-receptors was lower than that of nicergoline. The level of monoamine metabolites (HVA and DOPAC for dopamine, MOPEG-SO4 for noradrenaline and 5-HIAA for serotonin) was taken as a measure of their turnover in the rat brain. A single dose of nicergoline (20 mg/kg, s.c.) strongly enhanced noradrenaline turnover, less that of dopamine. These effects, probably due to the interaction with alpha-receptors, were more marked after parenteral than oral administration. MMDL shared nicergoline's effect on dopamine and MDL that on noradrenaline, but they were less active than the parent compound. The most interesting results were obtained after chronic treatment (6-7 weeks) with rather low doses: 5 mg/kg b.i.d. of nicergoline and equimolar doses of the metabolites. Nicergoline and MMDL both enhanced dopamine turnover, especially in mesolimbic areas. In conclusion, the present report confirms and extends previous results on nicergoline's effects on catecholamine turnover and shows that its metabolite MMDL shares its effects on dopamine. Finally, it is particularly interesting that both ergolines were more effective in old than in young rats. PMID- 2906798 TI - Potentiation of dopamine receptor-mediated responses by B-HT 920 in mice. AB - The effect of B-HT 920, an alpha 2-agonist, on postsynaptic dopamine receptor mediated stereotypic behaviour, was studied in mice. Apomorphine produced typical stereotypic responses in mice such as sniffing, rearing, biting, licking and grooming. B-HT 920, when given alone, produced mild stereotypy. Pretreatment with B-HT 920 significantly potentiated the stereotypic behaviour of apomorphine. The specific alpha 2-blockers, idazoxan and yohimbine, failed to block the potentiating effect of B-HT 920. The specific D2-receptor blockers haloperidol and molindone, completely blocked the stereotypic responses due to B-HT 920 and apomorphine. On reserpinization of animals there was a 5-fold increase in stereotypy induced by the combination of apomorphine and B-HT 920. B-HT 920 also potentiated amphetamine-induced locomotor responses in mice in a haloperidol sensitive way. These data imply an interaction of B-HT 920 with postsynaptic dopamine receptors. PMID- 2906799 TI - [Disorders of neurohumoral regulatory mechanisms in sudden cardiac death]. AB - Trophic function of nervous system (NS) can be now defined as NS capacity for regulating metabolism at the level specific for age and performance status. It is also believed that NS can regulate relevant tissue differentiation employing a combined action of the afferent and efferent NS parts and mediators thereof. The conceptions of cardiac and vascular neurotropism have been recently enriched with evidence gained on quantitative histochemistry of adrenergic and cholinergic plexuses. Normal process of early cardiac desympathization occurs as a rule at the age of 35-60. Specific changes in different parts of autonomic nervous system and adrenal glands proceding sudden cardiac death are elicited. These presented with focal myocardial desympathetization, that of coronary vessels and conducting system which may produce zones of hypersensitivity to catecholamines prone to destabilization of cardiac function. PMID- 2906800 TI - [The development of biological concepts of depression]. PMID- 2906801 TI - Changes in activities of some ammonia-metabolizing enzymes in the rat liver and the brain after chronic ethanol administration. AB - The changes in the activities of ammonia-metabolizing enzymes in liver and brain after ethanol intoxication has been investigated in rats. After administration of ethanol 30% (w/v) 6g kg-1 for 4 weeks we found an increase in liver glutamate dehydrogenase and glutaminase activity. In brain tissue the glutaminase activity was significantly higher and glutamate dehydrogenase was significantly lower. Glutamine synthetase activity in liver and brain was practically unchanged. The reasons for these changes in the activities of some ammonia-metabolizing enzymes in liver and brain after ethanol ingestion have been discussed. PMID- 2906802 TI - Amino acid neurotransmitters and their receptors in the brain synaptosomes of acute hepatic failure rats. AB - Ammonia contents in the brain stem and prosencephalon markedly increased in a rat model of acute hepatic failure induced by partial hepatectomy following CCl4 intoxication. In hepatic failure rats, synaptosomal glutamic acid (excitatory amino acid neurotransmitter) contents decreased significantly in the prosencephalon, and GABA (inhibitory amino acid neurotransmitter) contents decreased significantly in the brain stem. The molar ratio of glutamic acid to glutamine significantly diminished in the brain stem. Glutamic acid decarboxylase activity in the synaptosomes and the binding of [3H]glutamic acid and [3H]GABA to synaptosomal membrane preparations were unchanged in acute hepatic failure rats. These results indicate than an insufficiency of both excitatory and inhibitory neurotransmitter amino acids is induced by high ammonia contents in the synaptosomes of the brain stem during acute hepatic failure. PMID- 2906803 TI - Infrared spectroscopic analysis of salt bridge formation between cytochrome b5 and cytochrome c. AB - The infrared spectrum of a solution of a protein contains bands due to both the peptide backbone and the amino acid side chains. Generally, the bands due to the peptide backbone, between 1700 and 1600 cm-1, are analyzed to determine the secondary structure of the protein; the bands due to the amino acid side chains, between 1600 and 1500 cm-1, are largely ignored. When cytochrome b5 is mixed with cytochrome c, under conditions that favor ionic complex formation, changes are seen in protein secondary structure and also in a band at 1562 cm-1. The band at 1562 cm-1 is due to the side-chain carboxyl of Glu residues, rather than those of Asp residues that show a band at 1585 cm-1, and the changes in the band at 1562 cm-1 indicate that when the two proteins interact, three ionized carboxyl groups of Glu become involved in salt bridge formation. This result is identical with that obtained by previous theoretical studies and suggests that infrared spectroscopy may be a rapid and quantitative method for the study of ionic interactions between proteins. PMID- 2906804 TI - Fate of nucleotides bound to reconstituted Fo-F1 during adenosine 5'-triphosphate synthesis activation or hydrolysis: role of protein inhibitor and hysteretic inhibition. AB - The protein ATPase inhibitor entraps about five nucleotides in pig heart mitochondrial F1, one at least being a triphosphate [Di Pietro, A., Penin, F., Julliard, J.H., Godinot, C., & Gautheron, D.C. (1988) Biochem. Biophys. Res. Commun. 152, 1319-1325]. The fate of these nucleotides was studied during ATP synthesis driven by NADH oxidation in reconstituted inverted submitochondrial particles. Iodinated F1, containing 0.7 mol of endogenous nucleotides/mol, was first loaded with tritiated adenine nucleotides in the presence or absence of the protein inhibitor and then reassociated with F1-depleted submitochondrial particles (ASU particles) to reconstitute an efficient NADH-driven ATP synthesis. In the absence of the protein inhibitor, 1.7 mol of labeled nucleotides remained bound per mole of reassociated F1, 0.8-0.9 mol being rapidly exchangeable against medium ADP or ATP, as measured after rapid filtration through nitrocellulose filters. In the presence of the protein inhibitor, as many as 3.25 mol of labeled nucleotides remained bound per mole of reassociated F1. Under hydrolysis conditions where ATPase activity was highly inhibited, no release of tritiated nucleotide occurred. In contrast, under ATP synthesis conditions where the protonmotive force was generated by NADH oxidation, the progressive reversal of inhibition by the protein inhibitor was correlated to a concomitant release of tritiated nucleotide. When ATP synthesis became fully active, about one nucleotide was completely exchanged whereas more than three nucleotides remained tightly bound and did not appear to be directly involved in ATP synthesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2906805 TI - Dihydrofolate synthetase and folylpolyglutamate synthetase: direct evidence for intervention of acyl phosphate intermediates. AB - The transfer of 17O and/or 18O from (COOH-17O or -18O) enriched substrates to inorganic phosphate (Pi) has been demonstrated for two enzyme-catalyzed reactions involved in folate biosynthesis and glutamylation. COOH-18O-labeled folate, methotrexate, and dihydropteroate, in addition to [17O]-glutamate, were synthesized and used as substrates for folylpolyglutamate synthetase (FPGS) isolated from Escherichia coli, hog liver, and rat liver and for dihydrofolate synthetase (DHFS) isolated from E. coli. Pi was purified from the reaction mixtures and converted to trimethyl phosphate (TMP), which was then analyzed for 17O and 18O enrichment by nuclear magnetic resonance (NMR) spectroscopy and/or mass spectroscopy. In the reactions catalyzed by the E. coli enzymes, both NMR and quantitative mass spectral analyses established that transfer of the oxygen isotope from the substrate 18O-enriched carboxyl group to Pi occurred, thereby providing strong evidence for an acyl phosphate intermediate in both the FPGS- and DHFS-catalyzed reactions. Similar oxygen-transfer experiments were carried out by use of two mammalian enzymes. The small amounts of Pi obtained from reactions catalyzed by these less abundant FPGS proteins precluded the use of NMR techniques. However, mass spectral analysis of the TMP derived from the mammalian FPGS-catalyzed reactions showed clearly that 18O transfer had occurred. PMID- 2906806 TI - [Interaction of acetyl-CoA-carboxylase from the rat liver with alkylating amides of ATP and ADP]. AB - The interaction of 4-(N-chloroethyl-N-methylamino)-benzyl-gamma-amide ATP (I) and the corresponding beta-amide of ADP (II) with rat liver acetyl-CoA carboxylase was studied. Both analogs were shown to cause affinity modification of the enzyme. ATP and GoAS Ac protected the enzyme against inactivation. HCO3- increased the rate of carboxylase inactivation by analogs I and II (2.5- and 1.5 fold, respectively). The alkylating amides did not influence the rate of the bicarbonate-dependent [14C]-ADP-ATP exchange and inhibited the enzyme-catalyzed reaction of [14C]-CoAs Ac----CoAS Mal exchange, which testifies to the localization of the modified group in the CoAS Ac-binding site of the enzyme active center. Based on the affinity modification and analog size, it was found that the distance between the ATP- and CoAS Ac-binding sites of the enzyme active center can vary from 0.8 to 1.2 nm. PMID- 2906807 TI - Neuroleptic malignant syndrome. PMID- 2906808 TI - State-dependent movement disorder. PMID- 2906809 TI - Analysis of municipal refuse incinerator ashes for asbestos. PMID- 2906810 TI - Catecholaminergic innervation of the spinal cord in the North American opossum, Didelphis virginiana. AB - Axons presumed to contain catecholamines were visualized in the spinal cord of the spinal cord of the North American opossum using antibodies to tyrosine hydroxylase (TH) by an indirect antibody peroxidase-antiperoxidase (PAP) technique. Axons showing TH-like immunoreactivity (TH-IR) coursed primarily in the dorsal part of the lateral funiculus, although they were also present more ventrally. An occasional TH-IR axon was seen in the dorsal funiculus. Within the gray matter, TH-IR axons were distributed most densely within the intermediolateral cell column (ILC). Such axons were more numerous in the presumptive sacral parasympathetic nucleus than within the adjacent gray matter, but their density was less than that within the ILC. Many TH-IR axons were also found within laminae I-V and X, but the density of innervation in the ventral horn was relatively low. The brainstem origin of TH-IR axons in the spinal cord was studied using a combination of the retrograde transport of fluorescent dyes and immunofluorescence as well as the retrograde transport of horseradish peroxidase and PAP immunohistochemistry. The injections of retrograde markers were made at either cervical, thoracic or lumbar spinal levels. With both techniques, spinally projecting TH-IR neurons were located within the nucleus periventricularis hypothalami, the nucleus paraventricularis hypothalami dorsalis, the area hypothalamica posterior, the ventral part of the nucleus coeruleus, the nucleus coeruleus pars alpha, the lateral part of the nucleus reticularis pontis, and several nuclei of the ventrolateral medulla. Few or no cells within the parabrachial area, the region of the Kolliker-Fuse nucleus or the area adjacent to the superior olivary complex (the location of the A5 group of rats) provided TH-IR projections to the spinal cord. Our results suggest that catecholaminergic projections to the spinal cord of the marsupial opossum are similar in termination and origin to those described for rats and other placental mammals, but differences do exist. PMID- 2906811 TI - Genetic mapping and analysis of somatostatin expression in Snell dwarf mice. AB - Mice homozygous for the gene dwarf (dw) have elevated levels of somatostatin (SS) in extra-hypothalamic brain regions. By in situ hybridization, increased levels of SS mRNA were observed in regions shown previously to contain higher levels of the SS peptide. Thus, the rate of transcription and/or the stability of SS mRNA are affected by the dw mutation. Since both dw and the gene encoding SS, Smst, are located on mouse chromosome 16, two backcrosses segregating dw and Smst were used to determine whether dw is an allele of Smst. In one backcross, an inbred strain derived from the subspecies Mus musculus molossinus was used to provide a high degree of DNA sequence polymorphism. The gene order and map distances determined on this backcross were: (centromere) - Prm-1 - 7 - Igl-1 - 3 - Smst - 29 - dw - 15 - Sod-1 - 4 - Ets-2, demonstrating clearly that Smst and dw are distinct genes. Additional evidence against a primary role for SS excess in the pathogenesis of dw/dw mice was obtained by injecting normal newborn mice with a potent SS analog (cyclo II). In contrast to the pattern of cell loss observed in the dwarf anterior pituitary, the pituitaries of injected mice were indistinguishable from normal controls, further suggesting that the Smst locus is not the primary site of dw gene action. PMID- 2906812 TI - The blockage of ponto-geniculo-occipital waves in the cat lateral geniculate nucleus by nicotinic antagonists. AB - The cholinergic mechanism underlying the genesis of ponto-geniculo-occipital (PGO) waves recorded from the lateral geniculate (LG) nucleus was studied in reserpinized cats under urethane anesthesia. PGO field potentials and their related unit activities occurred spontaneously or were triggered by stimulation of the brainstem peribrachial (PB) area. It was found that PGO-related unit activities were strongly depressed by systemic or iontophoretic applications of nicotinic antagonists such as mecamylamine or hexamethonium but remained intact after similar applications of scopolamine. These results suggest that the genesis of thalamic PGO waves involves a nicotinic activation of relay neurons by PB cholinergic afferents. PMID- 2906813 TI - Microbiological and virological analysis of water from two water filtration plants and their distribution systems. AB - The microbial flora of the water produced by two water filtration plants and their drinking water distribution system were evaluated: the Pont-Viau (PV) and the Repentigny (RE) water filtration plants. Untreated water entering the plants contained 3.6 (PV) and 16.8 most probable number of infectious units (mpniu)/L (RE) enteric viruses and total coliform bacteria counts were 300,000 (PV) and 500,000 cfu/L (RE). Treated water leaving the plant was essentially free of all the bacterial indicators measured (total, stressed, and fecal coliforms; Aeromonas hydrophila; Pseudomonas aeruginosa; Clostridium perfringens; enterococci) as well as of human enteric viruses. Heterotrophic plate counts at 20 and 35 degrees C were low in the freshly treated water leaving the plants, but bacterial regrowth was observed in both distribution systems at all sampling sites. Average counts for the heterotrophic plate count (20 degrees C) were between 10(6) and 10(7) cfu/L and counts were clearly increased with the distance from the plant. The most numerous bacterial genera encountered were Bacillus, Flavobacterium, and Pseudomonas (nonaeruginosa). PMID- 2906815 TI - Clinical pharmacology of aggressive behavior. PMID- 2906816 TI - [Evaluation of the effects of acute loading changes on mitral insufficiency in patients with mitral valve prolapse. A color Doppler echocardiographic study]. PMID- 2906817 TI - Elevated levels of histamine metabolites in cerebrospinal fluid of aging, healthy humans. AB - The metabolites of histamine, tele-methylhistamine (t-MH) and tele methylimidazoleacetic acid (t-MIAA), were measured in lumbar cerebrospinal fluid of healthy, normal volunteers aged 20-31 (n = 4) and 60-72 (n = 8) by gas chromatography-mass spectrometry. Mean levels (pmol/ml) of t-MH, t-MIAA and the sum of t-MH and t-MIAA (2.9, 6.4 and 9.4, respectively) were significantly higher in CSF from older subjects than from younger subjects (1.1, 4.5 and 5.5, respectively). Another older subject had yet higher levels of metabolites (6.7, 15.1 and 21.8, respectively). The sum of the levels of the known metabolites of histamine in brain, i.e. t-MH and t-MIAA, did not overlap between the younger and older subjects. The levels of pros-methylimidazoleacetic acid, an endogenous isomer of t-MIAA that is not derived from metabolism of histamine, did not differ significantly between the two groups. These findings contrast with results of similar studies of metabolites of other aminergic transmitters in showing elevated levels of metabolites of histamine in cerebrospinal fluid with increasing age. PMID- 2906814 TI - Pertussis: the disease and new diagnostic methods. AB - Bordetella pertussis, the causative agent of whooping cough, produces an acute and chronic respiratory infection in infants and young children. B. pertussis is still a major health problem of young children throughout the world even though effective immunization against whooping cough is available. While predominantly a childhood disease, it has been reported also to be a cause of persistent cough in adults. This review discusses the numerous bacterial virulence factors that may play roles in the pathogenesis of pertussis and in immunity to infection. The present problems with pertussis diagnosis, recent advances, and future prospects for new and improved rapid diagnostics tests also are explored. PMID- 2906818 TI - Relationship between urotensin II- and somatostatin-immunoreactive spinal cord neurons of Catostomus commersoni and Oncorhynchus kisutch (Teleostei). AB - This immunocytochemical study describes the presence of separate immunoreactive (IR)-urotensin II (UII) and IR-somatostatin (SOM) systems in the spinal cord of two species of teleost fish. Both systems are arranged in a close spatial interrelationship in which IR-SOM fibres apparently innervate cerebrospinal fluid (CSF)-contacting IR-UII neurons. Specimens of Oncorhynchus kisutch also display CSF-contacting IR-SOM neurons located in the lateral ependymal walls of the central canal, in addition to CSF-contacting IR-UII neurons located ventrally. It is suggested that, in this species, CSF-contacting IR-SOM and IR-UII neurons perceive different stimuli from the CSF and are integrated in such a way that one peptidergic system may modulate the function of the other. PMID- 2906819 TI - The development of GABA-like immunoreactivity in the thoracic ganglia of the locust Schistocerca gregaria. AB - The development of GABA-like immunoreactivity was investigated in embryonic and juvenile locusts using an antibody raised against GABA-protein conjugates. GABA like immunoreactivity was first detectable in the neuropile of embryonic ganglia at 55% development, and in neuronal somata at 62% development. The total number of immunoreactive somata increased between 62% and 85% embryonic development, and followed an anterio-posterior pattern of expression. At 85% development, the number of immunoreactive somata reached adult levels and no change in number was then seen. In embryonic stages and first and second juvenile instars two dorsal and four ventral groups of somata were labeled in all three thoracic ganglia, whilst in later juvenile instars one of the dorsal groups was visible as a separate entity only in the metathoracic ganglion. These early patterns were modified by alterations in the positions of some of the groups during late embryogenesis and during juvenile development to produce the adult pattern. The results show that the development of GABA expression is similar to that of other neurotransmitters. The characteristics of the development of immunoreactivity indicate that some of these immunoreactive clusters may be derived from clonally related neurones. Finally, we demonstrate the presence of immunoreactive somata and processes in embryos, which correspond to those of identified local and intersegmental interneurones studied in the adult. PMID- 2906820 TI - Developmental changes of neuropeptides and amino acids in baboon cortex. AB - The pattern of developmental changes in concentrations of substance P, somatostatin and neuropeptide Y immunoreactivity and amino acids was studied in baboon cortex. Samples of occipital or frontal neocortex were obtained from preterm (100-105 days gestation), near-term (170-176 days gestation), and young adult animals. Substance P concentrations were low at preterm, highest at near term, and then declined to adult levels. Neuropeptide Y and somatostatin immunoreactivity increased steadily across the three age groups. Concentrations of aspartate and gamma-aminobutyric acid (GABA) also increased progressively from preterm to adulthood, whereas glutamate concentrations showed small increases that were not statistically significant. Concentrations of taurine and alanine were highest preterm and declined progressively to adulthood. Levels of neuropeptides and amino acids show distinct patterns of change during development of neocortex in the baboon. PMID- 2906821 TI - Diagnostic efficiency in discriminating liver malignancies from cirrhosis by serum gamma-glutamyltransferase isoforms. AB - Total GGT and GGT complexed with low-density-lipoprotein plus very low-density lipoprotein (LDL + VLDL) have been evaluated in sera from 53 healthy subjects, 23 patients with chronic hepatitis, 87 with liver cirrhosis and 50 with liver tumors (primary and metastatic). A cut-off of 20 U/l of GGT complexed with LDL + VLDL results in a diagnostic sensitivity of 84% for liver tumor patients, and a diagnostic specificity of about 80% towards the two groups of patients affected by cirrhosis or chronic hepatitis. This test, because of its high diagnostic efficiency, is a useful addition to the battery of laboratory tests that serve to discriminate cirrhosis and chronic hepatitis from liver malignancies. PMID- 2906822 TI - Dipeptidyl peptidase III and alanyl aminopeptidase in the human seminal plasma: origin and biochemical properties. AB - Human seminal plasma contained two distinct enzyme activities hydrolysing ArgArgNA. The enzymes were separated by anion exchange chromatography and further purified by gel filtration and/or hydrophobic interaction chromatography. The enzyme eluting at the lower NaCl concentration (0.26 mol/l) displayed an optimum at pH 5.7-6.0 (enzyme A), while the other enzyme eluted at 0.32 mol/l NaCl and showed an optimum at pH 8.5-9.0 (enzyme B). Enzyme A was found to coelute with an aminopeptidase which hydrolysed various amino acid derivatives as well as dipeptide naphthylamides sequentially. Both enzymes were sensitive to heavy metal ions (Cd, Cu, Hg, Pb) and chelating agents (EDTA, o-phenanthroline) and moderately sensitive to di-isopropylfluorophosphonate (DFP) or phenylmethylsulfonylfluoride (PMSF). After EDTA suppression both activities were partially reactivated by divalent metal ions, particularly by Co2+. Enzyme A was highly sensitive to amastatin, bestatin and puromycin, while enzyme B was not markedly influenced. With different substrates the modifier characteristics of enzyme A were equal. High concentrations of some substrates suppressed the hydrolysis rates of both enzymes. Enzyme B was much more sensitive to the thermal treatment than enzyme A. Tentative molecular masses of 110 kD and 80 kD were obtained for enzymes A and B, respectively. Enzyme B was found in all male reproductive tissues (testis, epididymis, vas deferens, ampulla, seminal vesicles, prostate), while enzyme A was only detected in the prostatic homogenate. Thus, ArgArgNA in the human seminal plasma is hydrolysed by dipeptidyl peptidase III, which may originate from different reproductive organs, while the prostate is responsible for the secretion of an aminopeptidase with a wide substrate spectrum including dipeptidyl derivatives. PMID- 2906823 TI - Infantile autism, fragile (X) (q27.3) and RFLP analysis in an extended Swedish family. AB - In an extended family with eight individuals with infantile autism, in association with other developmental disorders and fragile (X) (q27.3), DNA techniques were used to investigate linkage between X chromosomal probes and the disorder. F9 was not informative and recombination was found between fragile X and DXS15, DXS51 and DXS52. PMID- 2906824 TI - Further evidence for an association between the XbaI polymorphism at the apolipoprotein B locus and lipoprotein level. AB - Subjects with non-familial hypercholesterolemia who were homozygous for absence of an XbaI restriction site in the apolipoprotein B gene (genotype X2X2) had significantly lower values of apolipoprotein B than those possessing the site. Our data are in agreement with those of Berg (1986) and Law et al. (1986) indicating that X2X2 homozygotes have lower levels of apolipoprotein B, total serum cholesterol, triglycerides and LDL cholesterol. The mechanism underlying this effect is unknown, but could reflect different LDL metabolism between subjects with different genotypes. PMID- 2906825 TI - The Retzius cells in the leech: a review of their properties and synaptic connections. AB - 1. The Retzius cells (RCs) project an axonal branch in each anterior, posterior and dorsal segmental root. 2. RCs are the only serotonin-containing neurons projecting to the periphery. 3. RCs are activated by mechano-sensory neurons, by serotonin-containing neurons and by two pairs of subesophageal neurons, Tr 1 and Tr 2. 4. RCs also receive an excitatory and an inhibitory input from sensilla. 5. These inputs could form two systems, one converging onto RCs of each ganglion and one distributing to other ganglia after processing by RCs. 6. RCs play a role in muscle tension, in mucous release and in swimming activity. PMID- 2906826 TI - Environmental stressors during space flight: potential effects on body temperature. AB - 1. Organisms may be affected by many environmental factors during space flight, e.g., acceleration, weightlessness, decreased pressure, changes in oxygen tension, radiofrequency radiation and vibration. 2. Previous studies of change in body temperature--one response to these environmental factors--are reviewed. 3. Conditions leading to heat stress and hypothermia are discussed. PMID- 2906827 TI - Heart rates in the captive, free-ranging beaver. AB - 1. Heart rates of beaver (Castor canadensis) under free-ranging captive conditions for active behaviors and resting in water (approximately 121 beats/min) were significantly (P less than 0.01) higher than for resting on land (100 beats/min). 2. Although no transient recovery tachycardia was evident in swimming heart rates following diving, average swimming heart rates were higher (127 beats/min) after diving than after other precursor behaviors (123 beats/min). 3. Beaver exhibited bradycardia when sleeping (75 beats/min), diving (61 beats/min), and when threatened on land (57 beats/min). 4. The respiratory sinus arrhythmia indicated a respiratory rate of 15 breaths/min. 5. Cold temperatures (approximately 0 degree C) elicited higher heart rates than did warmer temperatures (approximately 20 degrees C) in active, non-diving behaviors (P less than 0.05). PMID- 2906828 TI - Renal excretion of urea in a small east African antelope, the dik-dik (Rhynchotragus kirkii). AB - 1. A study on the renal handling of urea by the dik-dik antelope (Rhynchotragus kirkii) was conducted. 2. Plasma and urine samples were analysed for osmolality, urea and creatinine concentrations during dehydration and intra-ruminal loading of potassium and sodium solutions. 3. The glomerular filtration rate (GFR) of the dik-dik was found to be 182.6 +/- 11.7 ml/min/100 kg body mass. 4. Dehydration was observed to increase tubular urea reabsorption and increase plasma and urine osmolalities, but had no effect on the amount of urea filtered at the glomerulus. 5. Potassium loading increased both GFR and urine flow rate. PMID- 2906829 TI - Presence and significance of lithium in the brown shrimp, Crangon crangon (L.). AB - 1. In female (non-ovigerous and ovigerous) brown shrimps, Crangon crangon, whole animal lithium levels are about 20% higher than in males, which indicates that lithium has a special function in the female reproductive system. 2. Decreasing lithium levels in larger males suggest that with males a substantial part of the lithium present may be passively absorbed to the exoskeleton. 3. At low temperatures internal lithium concentrations are strongly increased. In response to external salinity the internal lithium concentrations show a typical regulation pattern. The effects of temperature and salinity clarify that lithium must be involved in metabolic processes. 4. Apart from a special function in the reproductive system, lithium can probably replace other ions in their function, e.g. in regulating the activity of enzymatic processes. PMID- 2906830 TI - Heat production in growing pigs calculated according to the RQ and CN methods. AB - 1. Heat production, calculated according to the respiratory quotient methods, HE(RQ), and the carbon nitrogen balance method, HE(CN), was compared using the results from a total of 326 balance trials with 56 castrated male pigs fed different dietary composition and variable feed levels during the live wt range 20-120 kg. 2. HE(RQ) was generally higher than HE(CN). 3. HE(RQ) depended on feed composition and feed level and, consequently, on the synthesis and deposition of depot fat. For RQ-values above 1, HE(RQ) was overestimated. 4. HE(CN) was generally underestimated, because N- and C-balances in general were overestimated due to losses in excreta. 5. The difference between HE(RQ) and HE(CN) was not constant. It was smallest when fat synthesis and fat deposition were low (2-3.5%) and greatest when fat synthesis and fat deposition were high (7-9%). The presence of dietary fatty acids may affect the difference. 6. In pigs receiving a cereal based diet, HE(RQ) may be expected to give 3-4% higher values than HE(CN), but in case easily available carbohydrates (glucose, sucrose) or high-fibre diets are provided, the differences may be larger. 7. Both methods were carried out with similar accuracy and precision. The results indicated that both methods are equally reliable. PMID- 2906831 TI - Temperature-mediated processes in teleost immunity: homeoviscous adaptation by channel catfish peripheral blood cells. AB - 1. Channel catfish peripheral blood erythrocyte, thrombocyte, T cell and B cell membranes were assayed by fluorescence depolarization using the fluorescent probe 1,6-diphenyl-1,3,5 hexatriene (DPH) to determine the effects of in vivo temperature acclimation on membrane viscosity and the kinetics of homeoviscous adaptation. 2. Erythrocyte membranes did not undergo homeoviscous adaptation during the 8 week time period studied and were more rigid compared with those of the other cell types. 3. The kinetics of homeoviscous adaptation exhibited by membranes from T cells, B cells and thrombocytes differed: B cells required 1-3 weeks while T cells and thrombocytes each required 3-5 weeks. Membranes from T cells, B cells and thrombocytes from fish acclimated for relatively short times (less than or equal to 3 weeks) exhibited similar membrane fluidities. 4. T cells from channel catfish appeared not only to be sensitive to temperature but also to a factor(s) independent of temperature but correlated to long term in vivo acclimation, i.e. T cell membranes underwent additional decreases in membrane viscosity between 3 and 5 weeks. 5. In conclusion, it appears that low temperature-mediated immunosuppression of T cell functions in channel catfish is probably not due to an inherent non-adaptability or rigid nature of the T cell membranes. PMID- 2906832 TI - Glucose turnover and defense of blood glucose levels in Arctic fox (Alopex lagopus). AB - 1. Glucose utilization was assessed in fed and fasted arctic fox, maintained on a diet similar in composition to food available in the wild. 2. Fasted (24 hr) glucose concentration was not significantly different from the fed level (134 mg/dl). 3. Fasting was associated with a significant reduction in glucose space, pool size, total entry rate, and irreversible loss which suggests a decline in gluconeogenesis. 4. Glucose recycling was not significantly different between the fed and fasted states. 5. We suggest that, in the arctic fox, the mechanism for defending blood glucose levels during fasting is based on restricting blood glucose to tissues with a high glucose dependency. PMID- 2906833 TI - Tannins and digestibility in the steenbok (Raphicerus campestris). AB - 1. The influence of tannins on the digestion of a small ruminant was investigated. 2. A 1% tannic acid diet was compared with a normal diet. 3. The digestion of protein decreased by 7.04%, fibre by 9.77% and energy utilization decreased by 7.94%. 4. Tannic acid has a marked depressing effect on the digestibility of the steenbok. PMID- 2906834 TI - Effects of short-term changes in electrolyte intake on the adrenal steroidogenic responses of juvenile mallard ducks (Anas platyrhynchos). AB - 1. Adjusting the Na+ and K+ intake of juvenile mallard ducks caused the plasma concentrations of corticosterone (B) and aldosterone (Aldo) to increase independently of one another, but none of these changes in electrolyte intake had a significant effect on the deoxycorticosterone (DOC) concentration. 2. With the exception of DOC in birds consuming the control diet, the plasma concentration of each hormone, regardless of diet, increased significantly following exposure to stress. 3. Stress-induced increases in Aldo concentration were greatest in birds given diets containing low concentrations of Na+. 4. Unlike the mammal and some other species of birds, Na+ may be the primary secretagogue responsible for the regulation of both corticosterone and aldosterone synthesis in the mallard duck. PMID- 2906835 TI - Pineal melatonin content in photoperiodically responsive and non-responsive phenotypes of deer mice. AB - 1. The pineal melatonin content of photoperiod responsive and photoperiod non responsive male deer mice was assessed. 2. Pineal melatonin content did not differ between short-day mice with regressed testes or those that maintained their reproductive systems. 3. These data suggest that differential phasing of melatonin release or post-pineal mechanisms are responsible for the differential responsiveness to day length among deer mice. PMID- 2906836 TI - Properties of synaptic transmission at the neuromuscular junction of the squid, Loligo opalescens. AB - 1. Spontaneous and evoked synaptic activity were recorded from the muscles of squid fin and mantle. These spontaneous synaptic potentials were large (up to 30 mV) and pleomorphic. Their amplitudes were not normally distributed, nor did they appear to be clustered in integral multiples of some "unit" event size. 2. Electrical stimulation of the nerve resulted in muscle twitches when the bath calcium concentration was a third normal or higher. The frequency of spontaneous synaptic events was unaffected by low calcium. 3. The large size of spontaneous events may mean that the synchronized release of only a few such "quanta" are sufficient to cause muscle action potentials and contraction. 4. The shapes of spontaneous events correlated poorly with their amplitudes, which is consistent with release from multiple synaptic sites with distinct properties. PMID- 2906837 TI - Presence of pepsinogens immunoreactive to anti-embryonic chicken pepsinogen antiserum in fish stomachs: possible ancestor molecules of chymosin of higher vertebrates. AB - 1. Stomachs of adult teleosts and elasmobranchs reacted to an anti-embryonic chicken pepsinogen antiserum (anti-ECPg) as well as to an anti-adult chicken pepsinogen antiserum (anti-ACPg). 2. Zymograms and immunoblots of stomach extracts revealed that anti-ECPg- and anti-ACPg-reactive substances possess peptic activity. 3. The possible relationship between anti-ECPg-reactive pepsinogens in fish and prochymosins in higher vertebrates is discussed. PMID- 2906838 TI - Mechanosensory interneurons (MSIs) in the crayfish 6th abdominal ganglion are inhibited by activation of other MSIs. AB - 1. Identified mechanosensory interneurons (MSIs) in the 6th abdominal ganglion of the crayfish Procambarus clarkii have been shown to inhibit other projecting MSIs. 2. Interneurons sensitive to water-current stimulation of the tailfan, and which inhibited the tactile response of other MSIs when activated by depolarizing currents, were identified by iontophoresis of fluorescent dye. 3. Ten inhibitory interneurons have been identified, including both non-adapting, directional cells and phasic "touch" cells. 4. Inhibition triggered by activation of the identified cells was not widespread among fibers in the connectives. 5. Inhibition recorded intracellularly was mediated by compound inhibitory postsynaptic potentials of long duration (300-400 msec) and latencies of 13-15 msec, and therefore was apparently polysynaptic. 6. Depolarization and/or activity in MSIs, which modulates the stimulus response characteristics of related cells is a possible mechanism for contrast enhancement among directional or frequency-selective interneurons. PMID- 2906839 TI - Neuroendocrine changes produced by competition stress on the Thoroughbred race horse. AB - 1. Packed cell volume (PCV) and plasma catecholamines, cortisol and glucose were determined in blood samples obtained from race horses, after competition. 2. All these parameters were higher than basals but catecholamines increased 6-7 times while cortisol was enhanced only by 25%. 3. The increase of glucose and PCV was related to the rise of catecholamines. 4. In samples withdrawn after overnight stress caused by change of horseshoes, it was not possible to find values from basal values significantly different. 5. Influence of nervous temperament was observed only in the higher hematocrit found in basal conditions, particularly in females. PMID- 2906840 TI - Dynamics of FMRFamide immunoreactivity in response to physiologically active substances in the central nervous system of the snail, Achatina fulica. AB - 1. The changes in FMRFamide (Phe-Met-Arg-Phe-NH2) immunoreactivity in response to incubation in dopamine, serotonin, met-enkephalin, oxytocin, arg-vasopressin and FMRFamide were examined in the central nervous system of the snail, Achatina fulica. 2. When the central nervous system was cultured in medium which contained dopamine and in medium which contained serotonin, the number of immunoreactive neurons increased in the anterior part of the cerebral ganglion and decreased in the sub-esophageal ganglion. 3. When arg-vasopressin was added to the culture medium, the number of immunoreactive neurons increased in the pedal ganglion and decreased in the other sub-esophageal ganglion. 4. By contrast, when the central nervous system was cultured in medium which contained oxytocin, the number of immunoreactive neurons did not increase, but rather decreased, in each ganglion. 5. No changes in immunoreactivity were detected in the central nervous system when it was cultured in medium which contained FMRFamide. 6. It appears, from these results, that the production and release of FMRFamide from different neurons are differentially affected by the physiologically active substances tested. PMID- 2906841 TI - Coexistence of FMRFamide, met-enkephalin and serotonin in molluscan neurons. AB - 1. Coexistence of FMRFamide, met-enkephalin and serotonin immunoreactivities was examined in Achatina fulica and Aplysia kurodai. 2. Coexistence of FMRFamide and serotonin was found in some neurons of the visceral, right parietal and pedal ganglia of Achatina fulica, and in the pedal ganglion of Aplysia kurodai. 3. In Achatina fulica, coexistence of FMRFamide and met-enkephalin was found in a neuron of the left parietal ganglion and that of met-enkephalin and serotonin was found in a giant neuron of the right parietal ganglion. 4. Based on these results, the biological significance of coexistence was discussed. PMID- 2906842 TI - Glucagon auto-immunization fails to stimulate food intake or growth in young rabbits. AB - 1. To further investigate the possible role of glucagon in appetite control, weaned rabbits were auto-immunized using a glucagon-bovine serum albumin conjugate (G-BSA). 2. At weekly intervals, the animals were weighed and blood samples collected and subsequently analysed for insulin, glucose and glucagon concentrations. Weekly food consumption was also recorded. 3. At the termination of the experimental period, each animal was subjected to a glucose tolerance test. Following this procedure, the animals were killed and the livers excised and frozen for subsequent glycogen determination. 4. No differences between the controls and auto-immunized group were found at any time for weekly weight gain, food intake, blood glucose or insulin concentrations. 5. Glucagon concentrations in the control group remain stable over the 7 week period; however, after the third week of the experiment, no glucagon could be detected in the blood of any of the auto-immunized animals. 6. The auto-immunized animals had significantly different glucose tolerance profiles and also had significantly more liver glycogen than the control group. PMID- 2906843 TI - D-amino acid oxidase in mouse liver--II. AB - 1. Activity of D-amino acid oxidase was detected in tissue extract of mouse liver by two sensitive spectrophotometric methods. 2. The activity was also detectable in extracts of the heart, but not of lung. PMID- 2906844 TI - Characterization of A units released from the poly(A) tract of rabbit globin mRNA during protein synthesis: possible role of the released ATP in synthesizing protein. AB - 1. Rabbit globin mRNA poly(A) was translated in two cell-free synthesizing systems, rabbit reticulocyte lysate and wheat germ extract, to characterize the product released from the poly(A) tract during globin synthesis. 2. Kinetic studies indicate that the size of the cleaved nucleotide proves to be a monomer, as revealed by column chromatography on Sephadex G-100 or G-25. 3. Characterization of the monomer was accomplished by chromatography on DEAE cellulose. Initially, 5 min post-translation, the monomer was ATP only; however, at later times ATP, ADP, AMP and adenosine were detected. 4. The two synthesizing systems differed in that globin mRNA poly(A) was translated at a faster rate in the wheat germ extract as revealed by the appearance of ATP, whereas AMP was detected sooner in the rabbit reticulocyte lysate. 5. The results indicate that the A unit released from the poly(A) tract during mRNA poly(A) translation is a monomer, and that these metabolites may play a role in controlling protein initiation via the released ATP. PMID- 2906845 TI - Contact dermatitis due to the beta-blocker befunolol [corrected] in eyedrops. PMID- 2906847 TI - Enzymuria to detect tubular injury in workers exposed to lead: a 12-month follow up. PMID- 2906846 TI - Comparison of urinary enzyme pattern in renal transplant recipients receiving two different immunosuppressive regimens: azathioprine versus ciclosporin. PMID- 2906848 TI - Glomerular and tubular effects of ionic and nonionic contrast media (diatrizoate and iopamidol). PMID- 2906849 TI - Multiple aspects of the toxicity of fluroxene and its metabolite 2,2,2 trifluoroethanol. PMID- 2906850 TI - Regional mapping of unique DNA sequences from human chromosome 3 derived from a flow-sorted chromosome library. AB - Eight single-copy DNA probes specific for human chromosome 3 were isolated by screening a human chromosome 3-derived genomic library. Southern blot analyses of DNAs isolated from a panel of somatic cell hybrids allowed us to regionally assign all probes to subregions on chromosome 3. Three clones were localized to the short arm of chromosome 3 (3p21----pter), two to the long arm (3q21----qter), and three to the 3q21----3p21 subregion. Six of these DNA sequences map to regions overlapping a segment of chromosome 3 (3p14----p23) frequently deleted in small cell lung cancer cells. Restriction fragment length polymorphism analyses indicate that at least three of the eight single-copy probes studies show MspI or BglII polymorphisms. This library is a useful source of chromosome 3-specific probes. PMID- 2906851 TI - VNTR (variable number of tandem repeats) markers show loss of chromosome 17p sequences in human colorectal carcinomas. AB - Restriction fragment length polymorphisms at 53 autosomal loci were screened for heterozygosity in 40 colorectal cancer patients. The DNA pattern in constitutional versus tumor/polyp tissue was compared. More than half of the markers tested were of the VNTR (variable number of tandem repeats) type, giving the patient panel a higher informational content, since the frequency of individuals heterozygous for a particular marker is increased. Loss of alleles was revealed in 40% of the tumors from constitutionally heterozygous patients at the chromosome 17p loci, identified by the markers YNH37 and YNZ22. Similar losses were also detected on other autosomes, but at a significantly lower frequency. Our results suggest that hemi/homozygosity of 17p alleles plays a role in the development of a major subset of colorectal carcinomas. Similar observations regarding other autosomal loci may be interpreted as random losses in these tumors, or they may indicate loci important to minor clinical subclasses of colon carcinomas. PMID- 2906852 TI - Localization of the gene for acetyl-CoA carboxylase to human chromosome 17. AB - In situ hybridization was used to localize a cDNA probe of the acetyl-CoA carboxylase gene to human metaphase chromosomes. A significant proportion of the grains were situated over chromosome band 17q21. In situ hybridization to a t(6;17)(p25;q21.33) confirmed the location of the gene proximal to 17q21.33. PMID- 2906853 TI - Study of hamsters infected with epidemic hemorrhagic fever virus. PMID- 2906854 TI - [Study of the prevalence of tardive dyskinesia among psychiatric inpatients]. PMID- 2906855 TI - [A clinical analysis of 30 cases of affective disorder with rapid cyclic episodic features]. PMID- 2906856 TI - [An evaluation of the therapeutic safety of anti-psychotic agents: analysis of 104 mortality cases in the past 30 years]. PMID- 2906857 TI - [Preliminary study of schizophrenics with brain atrophy treated with antipsychotic drugs]. PMID- 2906858 TI - [Propranolol in the treatment of neuroleptic-induced akathisia]. PMID- 2906859 TI - [Analysis of the effective psychiatric spectrum of some antipsychotics]. PMID- 2906860 TI - [Rat family and virus carrying state in hemorrhagic fever with renal syndrome]. PMID- 2906861 TI - [Identification of the site of mediator release in the frog motor nerve ending using 3 extracellular microelectrodes]. PMID- 2906862 TI - [Polymorphic repetitive DNA sequences in genomes of wild and domesticated sheeps]. PMID- 2906863 TI - Contingency management in methadone maintenance: effects of reinforcing and aversive consequences on illicit polydrug use. AB - Treatment outcomes were compared for an intervention emphasizing reinforcement for abstinence from illicit drug use and an alternative intervention which combined the same reinforcement contingencies with aversive consequences for unauthorized drug use. Sixteen polydrug abusing methadone maintenance patients were randomly assigned to one of two treatment groups. Both groups received the opportunity to take methadone doses away from the clinic (take-home dose) as reinforcement for submitting urines testing negative for illicit substances. A regular weekly take-home dose of methadone could be earned for every 2 weeks of verified abstinence from unauthorized drugs, up to a maximum of three take-home doses per week. The combined intervention group had an additional contingency which involved a reduction in methadone dose as an aversive consequence for submitting urine samples testing positive for illicit substances. Specifically, 10% of the patient's daily methadone dose was lost for each week in which two of three urines tested positive for illicit drugs. An examination of the urinalysis results indicated no between group differences. Overall, 8% of the 12-week baseline urinalysis results tested negative for illicit substances while 42% tested negative for unauthorized substances during the 20 weeks of treatment intervention. At the end of the intervention period, nine subjects remained in treatment with three patients in each group receiving at least once weekly take home privileges. Of the seven subjects no longer in treatment, five were in the combined intervention group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2906864 TI - Influence of age on effects induced by intermittent ethanol treatment on the ethanol drinking pattern and related neurochemical changes in the rat. AB - Male rats were treated with one ethanol (2.0 g/kg i.p.) or saline injections once a week for 50 weeks. During this treatment period the rats had in addition access to ethanol (10% in drinking fluid) as a choice against water for 24 h prior to the injection. During the following evaluation period, animals had a continuous choice between ethanol and water and the concentration of the ethanol solution increased every 3rd week from 5 to 10, 15 and 25%, with 10% as a reference tested between the other concentrations. The animals were killed after an abstinence of 4 weeks, whereupon the concentrations of noradrenaline (NA), dopamine (DA), serotonin (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) were determined in the frontal cortex. In the remaining cerebral cortex, activity of monoamine oxidase, reuptake of NA and stimulated inositol phospholipid (PI) breakdown was also determined. Muscarinic binding sites were determined in the striatum. During treatment, saline injected rats had a constant voluntary 24 h ethanol intake. There was a decrease in the corresponding intake in the animals given the ethanol injections. The diminishing of the intake was more marked in rats starting treatment at an age of 19.4 weeks when compared to rats starting at an age of 5.4 weeks. In the evaluation period the ethanol intake was fairly constant for all groups. However, the regressions between intake of the reference concentration when plotted against the different tested concentrations were most marked in the group where ethanol injections started at an early age. In the total material there were significant F-values when concentrations of NA, 5-HIAA, 5-HT/5-HIAA in the cortex and muscarinic binding sites in the striatum were tested. Age could not be excluded as a contributing factor, but for muscarinic binding sites in the striatum, concentrations of DA and 5-HIAA in the cortex, and potassium stimulated PI breakdown in the cortex significant regressions with voluntary ethanol intake as dependent variable could be established. Since these intakes are stable, a causal relation with dependence may be involved. PMID- 2906865 TI - Xamoterol. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use. AB - Xamoterol is a partial agonist at the beta 1-adrenoceptor. Haemodynamic studies indicate that xamoterol moderately increases myocardial contractility, improves diastolic relaxation and lowers left ventricular filling pressure at rest and during moderate exercise. At higher levels of sympathetic activity (e.g. strenuous exercise) it produces negative chronotropic responses whilst the reduced filling pressure is maintained. Studies in patients with mild to moderate chronic heart failure demonstrate an advantage for xamoterol 200mg twice daily over placebo and digoxin with respect to improvement in exercise capacity and symptoms. In limited trials to date the initial response seems to be maintained during periods of up to 12 months. Preliminary small studies suggest that xamoterol is useful in the treatment of some patients with angina pectoris, sinoatrial disease or postural hypotension, although further studies are needed to confirm its clinical role in such patients. Xamoterol appears to be generally well tolerated, but deleterious effects in a small number of patients with asthma, or severe heart failure due to dilated cardiomyopathy indicate the need for cautious use of xamoterol in patients with these diseases. Thus, xamoterol is a promising addition to the drugs available to the physician for treating patients with mild to moderate heart failure although further controlled studies are required to clearly establish its precise role. PMID- 2906866 TI - Fetal and maternal plasma levels of gastrin, somatostatin and oxytocin after vaginal delivery and elective cesarean section. AB - We measured the cord levels of gastrin, somatostatin and oxytocin with radioimmunoassay in plasma collected from the umbilical artery after vaginal delivery and after elective cesarean section. Maternal venous samples after the two labour modalities were also assayed for the same hormones. Fetal gastrin, somatostatin and oxytocin levels were significantly higher after vaginal delivery than after elective cesarean section. Independently of labour type, the fetal gastrin and somatostatin levels were always higher than the maternal levels. We suggest that the observed high levels of gastrin, somatostatin and oxytocin could be due to a stress-related stimulation of the oxytocin- as well as of the gastric gastrin- and somatostatin-producing cells, occurring particularly during vaginal delivery. The significant inverse correlation found between fetal pH and the recorded hormone levels is consistent with this hypothesis. PMID- 2906867 TI - [Effect of the combined use of alcohol and dopaminergic agents during pregnancy on the function of the hypophyseo-thyroid system in the progeny of rats]. PMID- 2906868 TI - Enhancement of gamma-glutamyl transpeptidase expression in bone marrow cells by colony stimulating factors. AB - Studies on blood serum from mammary carcinoma (MC) hosts, which promoted gamma glutamyl transpeptidase (GGT) expression by normal rat bone marrow cells in liquid culture, were extended to various granulocyte-macrophage colony stimulating factors (CSFs). GGT concentration per cell was found to increase (without change in total cell number) by incubation for 48 h with purified CSF-2 gamma and CSF-1 (but not interleukin-3), with human giant cell elaborated GM-CSF and L-cell conditioned medium, as well as with the 3 MC preparations (host serum, MC extract and MC conditioned medium). GGT-inducing ability (per milligram protein) ranked the 7 preparations in the same order as did their proliferative effect (number of colonies per milligram protein) in the standard mouse bone marrow agar culture system. The quantitative correlation between these two kinds of activities (linear for their logarithmic values) was highly significant, r = 0.976, p less than 0.001. The alkaline phosphatase concentration of bone marrow cells in liquid culture was also increased in the presence of the same 7 preparations, and this again was proportional (r = 0.985, p less than 0.001) to their colony stimulating potential. PMID- 2906869 TI - Induction of gamma-glutamyl transferase by dexamethasone in cultured fetal rat hepatocytes. AB - Hepatocytes isolated as a relatively pure population from normal fetal rats were maintained in primary monolayer culture for 4-10 days. Hepatocytes exhibited a small increase in basal gamma-glutamyl transferase (GGT) activity over time. Exposure to dexamethasone (10(-6) mol/l) elicited a rise in GGT activity after a lag of 24 h. The presence of the steroid was necessary to maintain induction, and its removal resulted in reversal of induction. The maximal response was 2- to 3 fold, 72 h after exposure to the steroid. After this maximal response, a gradual decay in enzyme activity occurred, despite the continuous presence of the hormone. Actinomycin D or cycloheximide given prior to/or simultaneously with the steroid prevented the induction, thus suggesting that both RNA and protein biosynthesis are necessary for induction to occur. PMID- 2906870 TI - Effects of beta-adrenergic blockade on left ventricular relaxation and filling dynamics in coronary artery disease: a pulsed Doppler echocardiographic study. AB - Left ventricular (LV) filling as assessed by Doppler transmitral flow velocity measurements was studied in 20 male patients with coronary artery disease (CAD) and in 18 normal individuals. Stroke volume, blood pressure and heart rate in the two groups were not significantly different. Compared to normals, the ratio between early and atrial-induced peak velocities was significantly lower in the patients (1.2 +/- 0.3 vs. 1.40 +/- 0.3, P = 0.01), as was the fraction of transmitral filling during the first 1/3 of diastole (45 +/- 7% vs. 50 +/- 4%, P less than 0.001). Isovolumic relaxation time (IV R) was 96 +/- 13 ms in patients vs. 74 +/- 12 ms in normals (P less than 0.001). The CAD patients were treated with atenolol for 13-24 days. The velocity ratio increased by 30% (P less than 0.001) due to a 12% increase in early (P = 0.004) and an 11% decrease in atrial induced peak velocities (P = 0.01). Filling fraction and deceleration rate of early inflow both increased by 22% (P less than 0.001). IV R decreased by 8% (P = 0.01). After atenolol treatment, heart rate and blood pressure decreased by 23% and 10% (P less than 0.001), respectively, whereas stroke volume increased by 14% (P less than 0.001). Thus, CAD was associated with Doppler indices of retarded LV filling and myocardial relaxation. After atenolol treatment, significant increases in velocity ratio and filling fraction indicated a shift of filling from late towards early diastole, suggesting improved diastolic function. However, different factors related to beta-adrenergic blockade may have contributed to the observed changes. PMID- 2906871 TI - The hyperinsulinaemic hypoglycaemias in infancy: a study of six cases. AB - The aim of the present study was to evaluate various functional tests for the differentiation of hyperinsulinaemic hypoglycaemia. The pathophysiological and histological findings in six infants, aged 2-7 months, with persistent hyperinsulinaemic hypoglycaemia are described. Islet cell adenoma was found in four infants and pancreatic nesidioblastosis in two others. Circulating levels of blood glucose (BG), immunoreactive insulin and C-peptide immunoreactivity were measured under basal conditions and during both stimulation and suppression. The diagnosis of hyperinsulinaemia was made by estimation of the BG/serum insulin ratio, which was the most important diagnostic criterion of hyperinsulinism. Control subjects of comparable age showed a ratio of 8.3 +/- 4.4 (range 4.1 13.3), whereas the six patients had values between 0.3 and 5.1. At least four determinations with ratios lower than 2.6 were necessary for confirming the diagnosis. Preoperatively we performed oral glucose tolerance, diazoxide infusion, somatostatin infusion and C-peptide suppression tests. It is suggested that the various function tests, especially the suppression tests, do not differentiate hyperinsulinism caused by an adenoma from that caused by diffuse pancreatic nesidioblastosis. PMID- 2906872 TI - Reversible congenital neutropenia associated with maternal sulphasalazine therapy. PMID- 2906873 TI - Plasma prolactin, sex steroids and gastrin in human volunteers treated for 2 weeks with therapeutic doses of cimetidine or the new histamine H2-receptor antagonist ramixotidine (CM 57755A). AB - Three groups of eight healthy male volunteers received placebo for 2 days, then daily morning doses either of cimetidine 800 mg, ramixotidine 750 mg (CM 57755A), or placebo, for 14 days, and then were all returned to placebo for one more day. Plasma levels of prolactin, testosterone and 17 beta-estradiol were measured on Days 2, 3, 16 and 17 in blood samples taken 30 and 15 min before and 0, 60, 120, 180, 240 and 300 min after treatment. Gastrin was assayed in blood collected on the same days 180 min after treatment. Mean pre- and post-treatment areas under the time-concentration curves of the first three hormones were not significantly different in the three groups on any test day, or within the same group throughout the four test days. Mean plasma gastrin levels ranged between 27 and 42 pg/ml, respectively, in the placebo and cimetidine treated groups on test day 3, and intermediate values were found in the group receiving CM 57755A. There was no statistically significant difference in gastrin level between the groups on any test day or within the same group throughout the four test days. No subjective side-effects attributable to the treatments were reported, and there were no abnormalities in blood pressure, heart rate or standard laboratory tests. PMID- 2906874 TI - Ketanserin combined with a beta-blocker or diuretic in essential hypertension. A multicentre study. AB - The antihypertensive effect of ketanserin 40 mg b.d. in combination with a beta adrenergic blocking agent or a diuretic was assessed in an open study in 35 patients with essential hypertension, who had not responded to treatment with beta-blockers, diuretics or their combination. The ketanserin/beta-blocker combination decreased mean sitting systolic/diastolic blood pressure (SBP/DBP) from 169/107 mmHg to 156/91 mmHg at the end of the 12-week active treatment period. The decrease in systolic blood pressure was significant only at Week 8, while the decrease in diastolic blood pressure was highly significant at all times. A significant reduction in heart rate by 10 beats.min-1 was observed with the ketanserin + beta-blocker combination. The ketanserin/diuretic combination led to a significant reduction in mean SBP/DBP from 164/106 mmHg to 146/92 mmHg after 12 weeks, with no significant change in heart rate. Body weight slightly increased in both groups. There were significantly fewer adverse reactions with the ketanserin/diuretic combination than with the ketanserin/beta-blocker combination. The results indicate a potentially useful therapeutic role for ketanserin in combination with beta-blockers or diuretics. PMID- 2906875 TI - Penbutolol: pharmacokinetics, effect on exercise tachycardia, and in vitro inhibition of radioligand binding. AB - The pharmacokinetics of penbutolol 40 mg, its reduction in exercise-induced tachycardia, and the in vitro inhibition of radioligand binding to beta adrenoceptors by plasma have been investigated in 7 healthy volunteers. The peak penbutolol concentration of 285 ng/ml was observed 1.2 h after administration, and the maximum of 4'-OH-penbutolol of 4.76 ng/ml was found after 1.64 h. Penbutolol was detected for up to 48 h, and 4'-OH-penbutolol dropped below the limit of detection after about 10 h. The terminal plasma concentration of penbutolol declined with an average half-life of 19 h. The maximum reduction in exercise-induced tachycardia was 33 beats/min 2.6 h after taking penbutolol. There was still a significant reduction of about 7 beats/min after 48 h. This effect could be adequately explained by the concentration-time course of penbutolol in combination with Clark's model of the concentration-effect relationship. Antagonist activity in plasma caused 91% inhibition of radioligand binding in vitro to beta 2-adrenoceptors on rat reticulocyte membranes 1.6 h after intake of penbutolol. By 48 h after intake, radioligand binding was still significantly inhibited (23%). The in vitro inhibition of radioligand binding by plasma showed a linear correlation with the reduction in exercise-induced tachycardia for all phases of the workload. The time course of the reduction in heart rate was completely explained by the in vitro inhibition of radioligand binding. However, it was not possible to explain the in vitro inhibition of radioligand binding by the concentration-time course of penbutolol using a simple competition model, although both variables were based on the same sampling site. When the in vitro inhibition of radioligand binding was plotted against the penbutolol concentration at the same sampling times (with both variables transformed to multiples of the apparent inhibition constant) the discrepancy became even more apparent as time-related counterclockwise hysteresis. None of the known metabolites of penbutolol can explain the discrepancy between the penbutolol concentration and the inhibition of radioligand binding in vitro. It appears that an other active metabolite is formed, which contributes to the effect in vitro and in vivo and so can explain the observed discrepancy. PMID- 2906876 TI - Safety and pharmacokinetics of mifentidine after increasing oral doses in healthy subjects. AB - Eight healthy men were each given single oral doses of mifentidine 20, 40 and 80 mg, a new H2-receptor antagonist, in a four-way, double-blind, placebo controlled, cross-over, dose-proportionality study. No significant objective or subjective effects were noted. Mifentidine showed unusual pharmacokinetic behaviour, producing a significant secondary peak in the drug concentration profile. The plasma AUC of mifentidine increased linearly with dose (r = 0.983). The apparent plasma clearance was 38.1 l.h-1, 31.0 l.h-1, and 47.4 l.h-1 for the 20, 40 and 80 mg doses, respectively, and the corresponding terminal plasma half lives were 10.3 h, 12.0 h, and 8.6 h. About 20% of the parent drug was excreted in urine over 24 h. The renal clearance (9.41 l/h for 20 mg, 9.5 l/h for 40 mg, and 12.8 l/h for 80 mg mifentidine) indicates that some of the drug was excreted by active tubular secretion. The results indicate that mifentidine is safe after single oral doses up to 80 mg. The pharmacokinetics of the 20 and 40 mg doses were similar, but after 80 mg the total body and renal clearances were significantly greater than after the two lower doses. As the terminal plasma half life of mifentidine is longer than of other available H2-receptor antagonists, it may have clinical implications for once-a-day therapy of peptic ulcer diseases. PMID- 2906877 TI - Strychnine seizure potentiation by azaspirodecanedione anxiolytics in rats. AB - Buspirone, gepirone and ipsaperone administered intraperitoneally (40 mg/kg) to naive rats were found to be proconvulsive for strychnine-induced seizures. The dose of strychnine required to induce seizures in 50% of test animals (CD50) was 2.18 mg/kg in naive rats, while CD50s for rats treated with the azaspirodecanediones ipsaperone, gepirone and buspirone were 1.65, 0.97 and 0.70 mg/kg respectively. Azaspirodecanediones have high affinity for the 5-HT1A serotonin receptor, however, the specific 5-HT1A agonist, 8-hydroxy-2-(di-n propyl-amino)-tetralin (8-OH-DPAT) had no effect on strychnine seizure in naive rats (CD50 = 2.0 mg/kg). The strychnine specific proconvulsive effects of inferior olive lesions and buspirone were additive, resulting in a CD50 of 0.1 mg/kg. This observation indicates that the buspirone-induced decrease in strychnine seizure threshold does not require intact inferior olive-climbing fiber pathways. Cerebellar sites for possible azaspirodecanedione action are discussed. PMID- 2906878 TI - Novel antipsychotic drugs share high affinity for sigma receptors. PMID- 2906879 TI - Antagonist activity of the cyclic somatostatin analogue CTP at mu- but not delta- and kappa-opioid receptors involved in presynaptic inhibition of neurotransmitter release. AB - In the present study the opioid receptor antagonist properties of the conformationally constrained cyclic octapeptide D-Phe-Cys-Tyr-D-Trp-Lys-Thr-Pen Thr-NH2 (CTP), which is derived from somatostatin, were investigated, using in vitro functional paradigms of central mu-, delta- and kappa-opioid receptors. Activation of mu-opioid receptors by the enkephalin analogues DADLE or DAGO resulted in a strong inhibition (by 60-70%) of the (electrically evoked) release of [3H]noradrenaline (NA) from superfused cortical slices. This inhibitory effect was antagonized by CTP in a competitive fashion (pA2 value 7.7-7.9). Activation of kappa-opioid receptors by bremazocine selectively inhibited (by 45-50%) the release of [3H]dopamine (DA) from striatal slices, whereas activation of delta opioid receptors by DADLE caused an inhibition (by 55-60%) of striatal [14C]acetylcholine (ACh) release, but neither of these inhibitory effects was affected by CTP. By itself, CTP inhibited cortical [3H]NA release (by 35-40%), but it did not affect the release of [3H]DA nor that of [14C]ACh from striatal slices. The inhibitory effect of CTP was not antagonized by naloxone. The data indicate that CTP selectively antagonizes mu-opioid receptors, involved in presynaptic inhibition of NA release in the brain. In addition, the peptide by itself causes an inhibition of NA release via a non-opioid receptor-mediated process. PMID- 2906880 TI - Reinnervation of dopamine neurons by regenerating serotonin axons in the rat medial zona incerta. A combined radioautographic and immunocytochemical ultrastructural study. AB - Cellular relationships between serotonin (5-HT) axons and tyrosine hydroxylase (TH)-containing neurons were examined by combined (3H)5-HT uptake radioautography and TH immunocytochemistry in the medial zona incerta (ZI) of adult rats, 7 and 50 days after an intracerebral injection of 5,7-Dihydroxytryptamine (5,7-DHT). Seven days post-lesion, only rare, scattered (3H)5-HT-labeled axon terminals were apparent in the zone of the medial ZI accessible to intraventricularly injected (3H)5-HT. In contrast, in sham-injected animals (3H)5-HT-labeled varicosities were numerous and often observed adjacent to TH-immunoreactive perikarya and dendrites. Fifty days post 5,7-DHT injection, the density of (3H)5-HT-labeled terminals approximated that seen in sham-treated animals. At the ultrastructural level, these regenerated 5-HT axons were similar in size, shape and content to those observed in sham-operated rats. Also, as in sham, some of the (3H)5-HT labeled axons were directly apposed to TH-immunopositive labeled profiles. The latter included large dendritic shafts and dendritic spines, but only rare perikarya. In both sham- and 5,7-DHT-treated animals a few of the contacts between (3H)5-HT-labeled and TH-immunoreactive profiles exhibited an asymmetric synaptic differentiation. These results indicate that 5-HT fibers in the medial ZI, following regeneration, can reestablish normal relationships and even synapses with a given population of chemically identified cells. PMID- 2906881 TI - [The action of azepoxole on central alpha 2-adrenoreceptors]. AB - The effect of adrenomimetics on the central alpha 2-adrenoreceptors responsible for mydriasis was studied. It was found that alpha 2-adrenomimetic azepoxole (BHT 933) exerts no effect on the central alpha 2-adrenoreceptors providing mydriasis. PMID- 2906883 TI - [The functional obligations of the feldsher (nurse) dealing with the problems of social care for drug abuse patient contingents]. PMID- 2906882 TI - [The fenazepam demand by rats depending on the degree of alcoholic motivation]. AB - Phenazepam stimulates the drinking behaviour of rats. Under free-choice conditions ethanol-preferring rats drank significantly greater amount of phenazepam solution than those not preferring ethanol. Intraperitoneal administration of phenazepam and ethanol eliminated differences between the animals of the two groups in consumption of each substance but had no cross effect. PMID- 2906884 TI - Production and characterization of monoclonal antibodies to the c-erbB-2 proto oncogene protein using a synthetic peptide immunogen. PMID- 2906885 TI - Mitochondrial protein targeting signals. PMID- 2906886 TI - Acrivastine in seasonal allergic rhinitis: two randomized crossover studies to evaluate efficacy and safety. AB - In two randomized crossover studies, the antihistamine, acrivastine, was evaluated for the treatment of seasonal allergic rhinitis. One study on 31 patients found both 4 and 8 mg acrivastine given three times daily to be significantly better than placebo for alleviating hay fever. There were no significant differences in symptom scores between the two doses, although more patients (63%) favoured 8 mg acrivastine over the 4 mg dose (46%) or placebo (35%). The other study found the higher dosage regimen to be similar in efficacy to 1 mg clemastine given three times daily. Both dosages were significantly better than placebo for reducing symptom scores in all 18 evaluable patients. The incidence of adverse experiences was low in both studies; there being no dose related effects of acrivastine. In the second study, drowsiness, probably or possibly treatment related, occurred on seven occasions during clemastine treatment and once with acrivastine. These studies indicate that 8 mg acrivastine given three times daily is both well tolerated and of equal efficacy to clemastine for the treatment of seasonal allergic rhinitis. PMID- 2906887 TI - A comparative tolerance study of terfenadine-pseudoephedrine combination tablets and pseudoephedrine tablets in patients with allergic or vasomotor rhinitis. AB - In this multicentre, double-blind, randomized, parallel group study, 315 patients with allergic or vasomotor rhinitis were treated on a twice daily dosing schedule with either a 60 mg terfenadine-120 mg pseudoephedrine hydrochloride combination or 120 mg pseudoephedrine hydrochloride (extended release) for 2 weeks. No clinically significant differences between the two groups were noted in body weight, temperature, respiration rate or blood pressure following the treatment period. An increase in mean heart rate of approximately 5 beats/min from entry to the final clinic visit was noted in both treatment groups. No clinically significant changes were noted in either treatment group when pre- and post treatment electrocardiograms were compared. There were also no clinically significant alterations in laboratory values, which included serum chemistry, haematology and urinalysis, within or between either group. The adverse events profiles for both groups were similar. The most frequent adverse event was insomnia, in 40 (25.3%) patients given the terfenadine-pseudoephedrine combination and in 42 (26.8%) of those given pseudoephedrine. No unusual or unexpected adverse events were reported. PMID- 2906888 TI - Prospective, randomized, double-blind comparison of benzalazine and sulfasalazine in the treatment of active ulcerative colitis. AB - Benzalazine (salicylazobenzoic acid, SAB), a 5-azo derivative of 5-aminosalicylic acid, has been designed as a new therapeutic agent for the treatment of inflammatory bowel disease which might lack the frequent side effects caused by the sulfapyridine moiety of the sulfasalazine molecule (SASP). Here, we report on a prospective, randomized, double-blind comparison of SAB and SASP in patients with an acute relapse of ulcerative colitis. 43 patients with an acute relapse of ulcerative colitis proven by the pertinent endoscopic-macroscopic and histologic criteria were randomized to receive a 6-week course of either 1 g SASP (n = 21) or the equivalent dose of 0.72 g SAB (n = 22) three times a day. Both groups were comparable with respect to demographic data, previous duration and extension of the disease as well as clinical, endoscopic and histologic severity of the relapse. 1 patient on SASP had to be removed from the study due to side effects, while 3 patients on SAB were removed due to rapid worsening of the disease requiring either surgery (1 patient with toxic megacolon) or additional steroid treatment (2 patients). 2 SAB patients were lost to follow-up after substantial improvement had been observed within the first 3 weeks of treatment. In the remaining patients (20 SASP, 17 SAB), stool frequency, stool consistency and macroscopic appearance as well as histology of the diseased mucosa were improved within 6 weeks, with no significant difference between the two groups with respect to any of the parameters recorded. Side effects were recorded in 5 patients on SASP (3 with nausea, 1 with pruritus and 1 with a generalized exanthema) and in 3 patients on SAB (all nausea and vomiting; difference not statistically significant). We conclude that SAB and SASP in equivalent doses are of similar efficacy in the treatment of active ulcerative colitis. PMID- 2906889 TI - [Organization and primary nucleotide sequence of 5S rRNA genes in barley Hordeum vulgare]. AB - A BamHI DNA fragment of 301 bp corresponding to the main repeating unit of 5S rRNA was isolated from barley genomic DNA. The primary nucleotide sequence of this fragment was determined and a high level of homology was found between coding sequences of 5S rRNA genes of barley, wheat and rye. At the same time, spacer's nucleotide sequences of different species of cereals were changed dramatically. At least two types of 5S rRNA tandem repeats of 301 and 450 bp were found in barley genome. Polymorphism for restriction fragment length in 5S rRNA repeats allowed to discriminate between all barley varieties used in this work. PMID- 2906890 TI - Diagnosis and management of rhinitis during pregnancy. AB - Chronic nasal symptoms occur commonly in pregnant women. The most frequent causes of rhinitis during pregnancy are allergic rhinitis, bacterial rhinosinusitis and rhinitis medicamentosa. The appropriate diagnosis in the individual pregnant woman can usually be established on the basis of the history, physical examination and nasal cytology. Benefit-risk considerations in the management of gestational rhinitis are discussed in detail. PMID- 2906891 TI - [Status of the blood circulation system in senior secondary school students during their studies]. PMID- 2906892 TI - [Ways of further solving theoretical and practical problems regarding the prevention of dust-induced occupational diseases of the respiratory organs (data of the 2nd international symposium. Czechoslovakia, September 22-27, 1986)]. PMID- 2906893 TI - [Collagenous colitis]. PMID- 2906894 TI - Analysis of soluble Entamoeba histolytica antigen using enzyme-L inked electroimmunotransfer blots. AB - Soluble antigens of ten strains of E. histolytica were studied by sodium dodecylsulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and enzyme-linked electroimmunotransfer blots (EITB). No relations of immune replicas to virulence, geographical origin and method of cultivation (xenic or axenic culture) were found. Antigens of all ten strains tested precipitated with anti-E. histolytica human serum in the area of 30-43 kD. Antigen of HK-9 strain created in this area a characteristic pattern with all sera containing the specific anti-E. histolytica antibodies and, therefore, EITB can be used for excluding false positive results in ELISA. PMID- 2906895 TI - The effect of tolypin in Tolypocladium niveum crude extract against mosquito and blackfly larvae in the laboratory. AB - The efficacy of tolypin against mosquito and blackfly larvae was studied under laboratory conditions. It was tested against Culex molestus, Aedes aegypti, Anopheles maculipennis, Simulium noelleri and Odagmia ornata. A concentration 0.1 mg/ml caused 100% mortality in all species tested and a concentration 0.001 mg/ml caused 100% mortality only in the two species of blackflies used within 24 hours. PMID- 2906896 TI - Effects of promethazine on ischemic and reperfusion arrhythmias in rat heart. AB - The effects of the H1-receptor antagonists promethazine, mepyramine, and chlorpheniramine on ischemic and reperfusion arrhythmias were studied in the isolated perfused rat heart. Promethazine reduced both ischemic and reperfusion arrhythmias (2 x 10(-6)M-7.5 x 10(-6)M). Mepyramine and chlorpheniramine decreased these arrhythmias but at concentrations about 10 times higher. The H2 blockers cimetidine and ranitidine had no antiarrhythmic effect. Promethazine also: (i) increased release of noradrenaline by the heart; and (ii) increased coronary flow in the reperfusion period and in some mildly ischemic zones. It is proposed that promethazine exerts most of its antiarrhythmic effects by a nonspecific mechanism, possibly membrane stabilization; in addition, enhanced coronary flow may play a role. PMID- 2906897 TI - Bopindolol in the treatment of moderate hypertension: a dose-response study. AB - To determine the optimal antihypertensive dose of bopindolol, we performed a randomized double-blind study in parallel groups. After 15 days of placebo single blind, 115 hypertensive patients received daily for 28 days one of 4 doses: 0 mg (placebo), 0.5 mg, 1.0 mg, 2.0 mg. The reduction of supine diastolic blood pressure (BP) did not exhibit the pattern of a dose-effect relationship. The effect of 0.5 mg belonged to the plateau of the dose-effect curve (P = 0.1, analysis of variance). The reduction of heart rate (HR) followed a typical dose effect curve, with a plateau beginning with 1 mg (P = 0.02). A trend toward an increase in the incidence of side-effects with dosage was observed (P = 0.3). Thus, the optimal antihypertensive dose may be 0.5 mg or less. Previous studies not using parallel randomized groups suggested an antihypertensive dose ranging from 2 to 4 mg. This study confirms that the dose-effect curves of beta blockers on HR and BP are dissociated. The dose-effect curve of HR seems unsuitable for assessing the optimal antihypertensive dose of a beta blocker. PMID- 2906898 TI - Evaluation of the natriuretic and beta-adrenoceptor-blocking effects of tienoxolol in normal volunteers. AB - The beta-adrenoceptor blocking and diuretic properties of tienoxolol (150 mg and 300 mg) were investigated and compared to those of a placebo in a double-blind, cross-over trial in six healthy volunteers. Heart rate (HR), systolic and diastolic blood pressures, peak expiratory flow rate (PEFR) at rest and during vigorous exercise, plasma renin activity (PRA) and aldosterone levels at rest, and diuresis and urinary electrolyte excretion values were measured before and at intervals up to 24 h after oral administration of the drugs. In addition, the clearances of electrolytes, uric acid, and creatinine were calculated, as well as the fractional sodium excretion (Fe Na%) before and 4 h and 24 h after drug intake. Finally, tienoxolol plasma levels were measured. Tienoxolol significantly and dose-dependently reduced exercise-induced tachycardia. This effect started 1 h after drug administration, peaked between 4 h and 6 h (-12% and -17% from control values at 150 mg and 300 mg, respectively), and lasted at least 12 h. Resting HR was decreased at 300 mg (P less than 0.05), PRA was decreased at both doses (P less than 0.05), but PEFR was not drug-affected. 24-h cumulative sodium excretion was increased (+24% at 150 mg [NS], +38% at 300 mg [P less than 0.01]) as compared to placebo, and Fe Na% did not change, regardless of the dose administered. 24-h cumulative diuresis was moderately increased by tienoxolol (NS), whereas creatinine clearance rose after the 300-mg dose, suggesting that tienoxolol might increase glomerular filtration rate. Plasma aldosterone levels remained unchanged. Finally, the elimination half-life of tienoxolol was 7.5 h. Thus, in healthy volunteers, tienoxolol behaves as an early acting and relatively long-lasting selective beta 1-adrenoceptor blocking drug endowed with significant natriuretic properties. PMID- 2906899 TI - Distribution of microtubules during the first meiotic cell division in the mouse oocyte: effect of taxol. AB - Mouse oocytes were stained by antitubulin antibody and by an anti-MAP1 antibody (JA2) during the first meiotic cell division. At germinal vesicle stage, JA2 antibody exclusively stains the nucleoplasm. When the nuclear envelope breaks down (GVBD) (2-3 h of culture), numerous foci of microtubules appear around the disrupting nuclear envelope; they are decorated by anti-MAP1 antibody. After 10 12 h of culture, the antigen component detected with anti-MAP1 antibody is present in the meiotic spindle. The antimitotic agent taxol (10 microns) induces microtubule formation, mainly at the periphery of the germinal vesicle. At GVBD, taxol provokes the formation of a large microtubular array stained with both antibodies, which is associated with the condensed chromosomes. Furthermore, numerous cytoplasmic asters become visible in the cytoplasm. At metaphases I and II, taxol induces an important enlargement of the metaphase spindles and increases the number of cytasters. PMID- 2906900 TI - Intratesticular injection as a method to assess the potential toxicity of various agents and to study mechanisms of normal spermatogenesis. AB - To better understand, to optimize, and to validate the technique of intratesticular (i.t.) injection, several parameters related to i.t. injection were examined. Volumes exceeding 50 microliters could be injected i.t.; however, testes frequently became excessively turgid and backflow of injected fluids occurred. Thus, a volume of 50 microliters or less was deemed optimal for injection. To determine the rate of distribution of substances throughout the testis, trypan blue was injected i.t. near the caudal pole of the testis, and the movement of dye was monitored. Within 2 min, the dye had spread approximately 1 cm from the site of injection, and in 5 min it had spread twice that distance. In 2 h, the dye had become distributed throughout the testis except at its extreme cranial pole. Seminiferous tubules did not take up dye, indicating that the spread of dye was via peritubular lymphatics. Seminiferous tubule histology appeared virtually unaffected by i.t. injection, even at regions adjacent to the site of injection, when a sterile 26-gauge or smaller bore needle was utilized. To determine disappearance from the testis, radiolabeled inulin was injected i.t. Half time for absorption was achieved at 1.75 h. Potential vehicles were explored in which compounds with a variety of physical properties could be injected. Gum tragacanth, normal saline, ethylene glycol, dimethyl sulfoxide (DMSO) mixed 1:1 with normal saline, sesame oil, and propylene glycol were found to be suitable injection vehicles, whereas ethanol, dissolved in normal saline in concentrations as low as 0.5% was found unsuitable. To assess vehicle efficiency, various vehicles were utilized with a known testicular toxin (taxol) and injected into one testis, and the histology was compared with the contralateral testis injected with vehicle alone. All vehicles, found suitable above, allowed dispersion of taxol to influence areas distant from the site of injection. Intratesticular injection assesses the potential of agents to directly affect the testis, and systemic metabolism is avoided. Their rapid spread throughout the lymphatics of the testes allows seminiferous tubules to be exposed to agents in innocuous vehicles more rapidly and in higher concentration than is often possible when using systemic injections. PMID- 2906901 TI - Perinatal anti-androgen treatment and genotype affect the mesotelencephalic dopamine system and behavior in mice. AB - Sex and strain differences in tyrosine hydroxylase activity (TH) of brain dopamine systems have been reported for mice. To investigate if there might be a causal relationship between perinatal androgen secretion and regional mesotelencephalic TH activity, BALB/cJ and C57BL/6ByJ male mice were treated perinatally with cyproterone, a steroidal anti-androgen (or vehicle), and orchiectomized at 1 month of age. Two-way analysis of variance indicated significant treatment and strain effects in the mesencephalon and tuber olfactorium: perinatal cyproterone treatment lowered TH activity, and BALB/cJ had higher regional TH activities than those of C57BL/6ByJ. The most prominent behavioral effects of cyproterone treatment were found in the expression of scratching, which was considerably increased in both strains. Possible implications of these results are discussed. PMID- 2906902 TI - DNA polymorphisms of the insulin receptor gene in Japanese subjects with non insulin-dependent diabetes mellitus. AB - Genotypes identified by two restriction fragment length polymorphisms (RFLPs) of the insulin receptor gene (IRG) with the restriction endonuclease Sst-1 were determined in a Japanese group comprising 51 patients with non-insulin-dependent diabetes mellitus (NIDDM) and 50 control subjects. Southern hybridization using a probe for the beta subunit of the human IRG identifies 4 alleles, termed S1(+) (5.3 kb), S1(-) (5.8 kb), S2(+) (7.0 and 2.4 kb) and S2(-) (9.4 kb). The frequencies of genotypes possessing the S1(-) allele in Japanese controls and Japanese NIDDM patients were 0.11 and 0.16, respectively. Unlike the previously reported association of the S1(-) allele with NIDDM found in Caucasians there was no significant difference in the frequency of the S1(-) allele between non diabetic and NIDDM Japanese patients. There was a significant difference in the frequency of the S2(+) allele between Caucasian control subjects (0.14) and Japanese controls (0.0) and NIDDM patients (0.02). PMID- 2906903 TI - Rare apolipoprotein E variant cosegregating with a unique APOE-C1-C2 haplotype in a normolipidemic family. AB - The genes coding for the apolipoproteins E, C1 and C2 are clustered on the long arm of chromosome 19 in a region of approximately 45 kilobases (kb). In a normolipidemic individual, we detected a new apoE variant with an isoelectric point between that of E3 and E4. As this variant lacks cysteine residues and has probably arisen from an E*4 allele, it is designated E4*. To gain further insight into the origin of the mutation, the haplotypes of the propositus were extended by restriction fragment length polymorphism (RFLP) analysis of the family. The apoE variant cosegregates with the H2 allele of the HpaI polymorphism visualized with an APOE probe and with a new rare 4.5-kb fragment (T3) of the TaqI RFLP detectable with an APOC2 probe. As the propositus and the first-degree relatives with this unique haplotype are normolipidemic, this apoE variant does not seem to be associated with disturbances in the lipoprotein metabolism. PMID- 2906904 TI - Familial porphyria cutanea tarda: hybridization analysis of the uroporphyrinogen decarboxylase locus. AB - Familial porphyria cutanea tarda (PCT) results from a deficiency of uroporphyrinogen decarboxylase (URO-D) activity. Hybridization analysis of genomic DNA from unrelated normal individuals and PCT pedigree members failed to detect any major deletions, rearrangements or restriction fragment length polymorphisms at the URO-D locus. PMID- 2906905 TI - Restriction fragment length polymorphism of the D1S1 locus in Italy. AB - Three Italian populations were examined for a restriction fragment length polymorphism probing with a DNA sequence of unknown function located on chromosome 1. No difference was observed between the samples. The allele frequencies in Italy were: D1S1 BS = 0.82, D1S1 BF = 0.18. PMID- 2906907 TI - Expression of the Thy-1 gene in human T lymphoid cell lines. AB - We have previously shown that three human T cell lines (MOLT-3, HUT-78 and HUT 102) were able to react with anti-human brain Thy-1 sera by cell surface immunofluorescence. However, the possibility that the antisera might cross-react with molecules other than Thy-1 could not be entirely excluded. In this report, mRNA prepared from these three T cell lines as well as from a murine T cell line (EL4) and a human B cell line (Raji) was subjected to Northern blot analysis and probed with a murine Thy-1.2 gene fragment. The result confirms our cell surface immunofluorescence data and indicates that HUT-78 and HUT-102 cells have approximately 20-fold more of the Thy-1 mRNA than MOLT-3 cells do. The Thy-1 mRNA was not detectable in the human B cell line Raji. This work is the first demonstration that the Thy-1 gene is expressed in human T cell lines. The finding is helpful in clarifying the current confusion regarding the expression of Thy-1 in human lymphoid cells and it also provides a possible model system for exploring the function of Thy-1 in cultured human T lymphocytes. PMID- 2906906 TI - Detection of Thy-1 on cell surface of human T lymphoid cell lines by a monoclonal antibody. AB - A mouse IgG2b(kappa) monoclonal antibody (MAb) HB-2S-1 against human brain Thy-1 was secreted by a hybridoma clone after fusion of mouse myeloma cells with spleen cells from a mouse that went through a prolonged immunization procedure before fusion. When tested against isolated human Thy-1 by the enzyme-linked immunosorbent assay (ELISA), MAb HB-2S-1 in culture supernatant showed a titer of over 100,000, and a titer of over 10 million in ascites of a mouse injected with the hybrid clone. By immunoblotting, this antibody was found to bind a doublet of protein bands of approximately 25,000 daltons among all proteins solubilized by deoxycholate (DOC) from membrane of human brain cells. When tested on human lymphoid cell lines by immunofluorescence, MAb HB-2S-1 strongly stained four T lymphoma cell lines, C91-Pl, HUT-102, HUT-78, and C5-MJ; and weakly two leukemia cell lines, MOLT-3 and Jurkat(clone E6-1). It did not stain a third T leukemia cell line, CCRF-CEM; a human B cell line, Raji; a plasmacytoma cell line, HMy2; or a myelomonocytic cell line, HL-60. Peripheral blood lymphocytes from ten normal human adults and the viable T cells isolated from another normal individual were also negative. PMID- 2906908 TI - Iron exerts a specific inhibitory effect on CD2 expression of human PBL. AB - The effect of in vitro exposure to ferric citrate (Fe-citrate) on the expression of human lymphocyte surface markers was studied. The following markers were examined: E-rosette formation, CD2, CD3, CD4, CD8, CD1, CD22, CD10 and HLA-DR. Pretreatment of peripheral blood lymphocytes (PBL) with Fe-citrate at concentrations ranging from 10(-2) M to 10(-5) M resulted in the exclusive inhibition of E-rosette formation and CD2 expression. None of the other surface antigens examined appeared to be sensitive to the Fe-citrate treatment. Competition experiments further indicated that iron interacts specifically with CD2 on T lymphocytes. PMID- 2906909 TI - Benzodiazepine abuse and management of anxiety in the community. AB - Medication is largely inappropriate in the management of anxiety, and benzodiazepines are not apparently effective in the minor affective disorders commonly seen in general practice (Catalan and Gath, 1985). Enough has been said to indicate that other measures are likely to be more helpful and to reduce the tendency to prescribe benzodiazepines. The taking of these drugs threatens to become epidemic and while medical agencies are by no means the only sources, sensible prescribing will go--and may already have gone, as the DHSS (1986) figures suggest--some way toward limiting consumption of these drugs. The DHSS needs to record more specific data relating to benzodiazepine use and abuse. Comparative trials of benzodiazepines and alternative non-benzodiazepine methods of anxiety management need to be set up as matter of urgency. The (no doubt) false impression that the pharmaceutical industry is dragging its feet in planning and sponsoring such trials should be speedily dispelled. Benzodiazepine prescribing, if it increases, may well in itself become a major danger to public health. PMID- 2906910 TI - Improvement of inpatient treatment of the alcoholic as a function of neurotransmitter restoration: a pilot study. AB - We report results of a double-blind evaluation of the nutritional supplement SAAVE for facilitating improvement in a 30-day inpatient alcohol and drug rehabilitation center. SAAVE is uniquely designed to elevate levels of enkephalin(s), serotonin, catecholamines, and GABA, which are believed to be functionally deficient in alcoholics. Twenty-two patients were studied. The SAAVE patients, as compared to the control group (a) had a lower BUD (building up to drink) score, 1 vs 2; (b) required no PRN benzodiazepines, 0% vs 94%; (c) ceased tremoring at 72 h, as compared to 96 h; and (d) had no severe depression on the MMPI, in contrast to 24% of control group. These preliminary data suggest that SAAVE is a valuable adjunct to therapy by aiding the patient's physical adjustment to a detoxified state while facilitating a more positive response to behavioral therapy. PMID- 2906911 TI - Beta blockers may induce in C57BL/6 mice a polyclonal activation of lymphocytes which is not mediated by beta adrenergic receptors. AB - The in vivo immune effects of nine beta (beta)-blockers are studied in C5B1/6 mice after 7 days of treatment. Humoral and cellular studies indicate that several beta-blocking agents, particularly pindolol and acebutolol, may induce a polyclonal activation of lymphocytes. It may involve all the classes and subclasses of immunoglobulins with a preferential effect on IgA and IgG2a. Further investigations, conducted using the laevorotatory and dextrorotatory forms of pindolol indicate that this immune effect is not mediated by specific beta-adrenergic receptors. PMID- 2906912 TI - Management of ectopic pregnancy: a shift from laparotomy to pelviscopy. PMID- 2906913 TI - Resistant cases of polycystic ovarian disease successfully treated with a combination of corticosteroids, clomiphene, and bromocriptine. AB - Eight successively examined anovulatory women with polycystic ovarian disease (PCOD) who had remained resistant to treatment with clomiphene and dexamethasone (DEX) (and some to hMG/hCG) and had mildly elevated prolactin levels were treated with a combination of clomiphene, DEX, and bromocriptine. There was a decrease in the LH:FSH ratio and androgen and prolactin levels to normal values; within five to eleven treatment cycles, all were pregnant. These results were probably achieved because of the inhibition of prolactin secretion by the dopamine agonist, but may also be due to repletion of a suggested possible functional depletion of dopamine within hypothalamic nuclei in PCOD. This combination treatment is therefore highly recommended before resorting to hMG/hCG therapy or surgery, both of which have intrinsic disadvantages. PMID- 2906914 TI - Smoking and cysts of the ovary. AB - Endocrinologic and epidemiologic data indicate that cigarette smoking is antiestrogenic. We found that cigarette smoking is significantly associated with the occurrence of cysts of the ovary among 5,398 college alumnae ranging in age from 21 to 80 years. Data on ovarian cysts were obtained in response to the question: "Did you ever have ovarian cysts? If yes, age occurred and treatment." The prevalence (lifetime occurrence) of cysts of the ovary in the entire sample is 10.2%. Never smokers had a lower lifetime occurrence of ovarian cysts in every age decade than did former smokers or current smokers. The age-adjusted odds ratio (OR) for ever smokers compared to never smokers is 1.5 with 95% CL (1.2, 1.8), P less than .001. For former smokers compared to never smokers, the OR is 1.5, 95% CL (1.2, 1.9); for current vs. never smokers, the OR is 1.4, 95% CL (1.1, 1.8). Smoking was also associated with the earlier occurrence of cysts of the ovary. The 2,622 former college athletes in the sample were at significantly lower risk of ovarian cysts than were the 2,776 nonathletes; OR = 0.8, 95% CL (0.6, 0.9). Young women need to be made aware of the possible adverse effect of cigarette smoking on the ovary. PMID- 2906915 TI - Five-year, multicenter study of a triphasic, low-dose, combination oral contraceptive. AB - A total of 4,342 women received a triphasic oral contraceptive combination containing levonorgestrel and ethinyl estradiol (Triphasil in the United States, Trinordiol in Europe) over a 5-year period, for a total of 70,282 cycles. Medication was begun on day 1 in the first cycle, with no backup contraception, and consisted of levonorgestrel (LNg) 50 micrograms + ethinyl estradiol (EE2) 30 micrograms for 6 days, LNg 75 micrograms + EE2 40 micrograms for 5 days, and LNg 125 micrograms + EE2 30 micrograms for 10 days. Twelve pregnancies occurred during the study, resulting in a Pearl Index of 0.22. Medication was missed in an overall total of 5,067 cycles (7.2%), and 9 of the 12 pregnancies were attributed by the investigators to misuse of the drug, resulting in a corrected Pearl Index of 0.06. Cycle control was excellent, bleeding irregularities were minimal, and the incidence of adverse experiences was low (generally less than 1% of total cycles). The results indicate that this triphasic combination, given in pharmacologic doses that are patterned after normal cycles, is a predictable, efficacious, well-tolerated, and accepted means of oral contraception. PMID- 2906916 TI - Wish for a child and infertility: study on 116 couples. I. Interview and psychodynamic hypotheses. AB - The authors wish to stress the importance of the psychosomatic approach in the investigation of infertility. Following the hypothesis that infertile patients may present emotional conflicts with regard to the wish of having a child, psychodynamic interviews were carried out with 116 infertile couples concomitantly with their first consultation at the Sterility Department. The psychological findings show that severe conflicts with regard to wish of parenthood were present in the majority of the female patients and especially in those without clinically defined organic infertility factors. The relationship between clinical diagnosis and psychological outcome was less evident in the male partners. The 11 pregnancies which occurred in the study group are also discussed with regard to the motivational quality of the wish of child of these patients. A recommendation is made that psychological interviews should be included in any infertility investigation as a matter of routine and that therapeutic procedures should take into account both the clinical and psychological diagnosis to prevent unsuccessful situations. PMID- 2906917 TI - Local hydrocortisone treatment of sperm-agglutinating antibodies in infertile women. AB - Local sperm-agglutinating antibodies (LSAA) in the cervical ovulatory mucus may be a cause of primary infertility. A group of 17 infertile women with LSAA treated without effect with artificial insemination and then condom therapy were studied. After hydrocortisone application to the ectocervix for up to four cycles, LSAA disappeared totally in 13 patients; six of them have given birth to babies. No side effects of treatment were observed. Hydrocortisone for local immunosuppression may become a new method of therapy in cervical immunological infertility. PMID- 2906918 TI - Effects of the posterior hypophysis and ovary on pheromonal production in normal females and in the reproductive behavior of male rats treated with D,L propranolol. AB - Posterior hypophysis homogenates of female rats stimulated with epinephrine subcutaneously contain a pheromonal factor that increments significantly the incidence of fertile coitus after having been placed in the oronasal groove of rats in proestro (69.2% fertile coitus vs. 36.6% of control). These same homogenates obtained from spayed rats increment reproductive activity even more (80.0% fertile coitus). The homogenates do not act by an intraperitoneal route. Male rats under the effect of high doses of D,L-propranolol reduce reproductive activity (21.2% fertile coitus). This effect is counteracted by posterior hypophysis homogenates from female rats stimulated with epinephrine, placed in the oronasal groove (72.2% fertile coitus). The homogenates of anterior hypophysis do not increase the reproductive capacity of rats in proestro, and do not modify the propranolol effects in male rats. PMID- 2906919 TI - Seminal plasma transferrin concentration in normozoospermic fertile men and oligozoospermic men associated with varicocele. AB - Seminal plasma transferrin concentration has been reported a useful clinical marker for Sertoli cell function. In the present study, to investigate if transferrin production in the testis is decreased in oligozoospermic men associated with visible varicocele, seminal plasma transferrin concentrations in two groups -12 normozoospermic fertile men and 14 oligozoospermic varicocele patients--were measured and the values compared. Seminal plasma transferrin concentration in the oligozoospermic varicocele group was 29.9 +/- 6.8 micrograms/mL, and the concentration in the normozoospermic fertile group was 75.5 +/- 39.3 micrograms/mL. There was a significant difference between the two groups (P less than .001). The results indicate that transferrin production in the testis of oligozoospermic varicocele patients must be decreased, and also suggest that decreased transferrin production may be related to disturbed spermatogenesis in varicocele patients. PMID- 2906921 TI - DNA polymorphism of the HLA-B35 gene associated to different HLA-C locus alleles. AB - Peripheral blood leukocyte DNA from 31 donors, previously typed as HLA-B35, was digested with EcoRV and analyzed by Southern transfer and hybridization to an HLA class I probe. Out of 31 HLA-B35 positive (+) individuals, 24 showed a 4.6-kb band, previously associated with the B35 allele by Cohen et al. (Proc Natl Acad Sci USA 80:6289-6292). The HLA-B35 allele has a strong linkage disequilibrium (70%) with the Cw4 allele. All samples having the 4.6-kb band corresponded to HLA B35+, Cw4+ cells, whereas those lacking the band came from HLA-B35+, Cw4-negative (-) cells. Five HLA-B35-, Cw4+ samples were also studied and none showed the band. An HLA-B locus-specific probe gave a strong hybridization signal to this fragment, whereas an HLA-C locus-specific probe revealed different bands. The results suggest that the 4.6-kb fragment contains the B35 gene. Digestion with other restriction enzymes, located the polymorphic site to the 3' end of the gene. Analysis of 18 additional individuals with other specificities of the "4c" antigenic cluster (HLA-B18, B51, B52 and B53) showed that the EcoRV/4.6 kb-band was also present in 5/5 B52 cells and 4/4 B53 samples. PMID- 2906920 TI - Urinary alanine-aminopeptidase (AAP) excretion in patients with urinary tract infection treated with ceftazidime (CAZ) or cefotaxime (CTX) plus tobramycin (TOB). AB - It is well known that some antibiotics are particularly nephrotoxic. In the present study we investigated kidney function and AAP excretion (as an index of nephrotoxicity) in patients with urinary tract infection treated with CAZ or CTX plus TOB. The main cause of infection was E. coli in both treated groups. After 10 days of treatment similar beneficial effects were stated in both groups. At the end of treatment urinary AAP excretion in both groups was higher than before treatment. Despite a significant increase in urinary AAP in only one patient of each group, the serum creatinine level rose by more than 45 mumol/l. Monitoring of urinary AAP may be useful in early detection of nephrotoxicity caused by antibiotics. PMID- 2906923 TI - Apparent loss of 2H4+ T cells in peripheral blood lymphocytes of normal donors: a 2H4-specific artefact unique to T cells. AB - The antigenic cluster designated CD45R is recognized by a family of monoclonal antibodies. However, one of those most frequently used because of its commercial availability is 2H4. In a series of experiments we show that 2H4 immunofluorescence is almost completely lost from CD4+ or CD8+ T cells of human origin if they are fixed after staining with 2H4. Loss of fluorescence intensity of the total population of 2H4+ lymphocytes and nearly complete quantitative loss of CD45R+ T cells is observed after fixation. This apparent loss of CD45R as detected by 2H4 is not seen if other CD45R-specific monoclonal antibodies are used. Fixation of B cells previously stained with 2H4 gives rise to slightly diminished fluorescence intensity, but no reduction in number of 2H4+ B cells. This appears to be due to a lower antigen density on T cells as compared to B cells. The effect is unique to 2H4, as other monoclonal antibodies recognizing CD45R, while exhibiting a decrease in fluorescence intensity after fixation, still unequivocally detect CD45R+ CD4+ or CD8+ T cells. The effect is restricted to human T cells, as primate lymphocytes, fixed after staining with 2H4, show no loss in fluorescence intensity. We conclude that if it is necessary to fix human T cells after fluorescent staining, the use of CD45R-specific antibodies other than 2H4 is mandatory. PMID- 2906924 TI - Tocainide-induced pulmonary toxicity. PMID- 2906922 TI - An HLA-DQ alpha allele identified at DNA and protein level is strongly associated with celiac disease. AB - An HLA-DQ alpha cDNA probe showed upon hybridization a highly significant discrepancy between the RFLP of celiac disease patients and healthy controls. The 4.0-kb Bgl II restriction fragment was present in 97% of celiac disease patients (n = 30), compared to 56% in a healthy control population (n = 72) (RR = 14.9; p less than 0.0005). At the product level all celiac disease patients tested to date have one DQ alpha chain in common, designated HLA-DQ alpha 2.3, which is associated with the 4.0-kb Bgl II fragment. This HLA-DQ alpha allele identified at the DNA level and product level seems to be a better marker for genetic susceptibility to develop celiac disease than those available to date. PMID- 2906925 TI - Malignant fibrous histiocytoma of the lung. PMID- 2906926 TI - Synchronous cystic hygromas. PMID- 2906927 TI - Myocarditis. PMID- 2906928 TI - Hypernephroma. PMID- 2906929 TI - Misplacement of the narrow-bore feeding tube. PMID- 2906930 TI - A pioneer Illinois physician and scholar. John F. Snyder, M.D. PMID- 2906931 TI - Inhibitory effect of ellagic acid on N-2-fluorenylacetamide-induced liver carcinogenesis in male ACI/N rats. AB - The effect of ellagic acid (EA) on the hepatocarcinogenesis induced by N-2 fluorenylacetamide (FAA) was investigated in male ACI/N rats. Rats were fed diet containing 200 ppm FAA and 400 ppm EA for 16 weeks, and diet containing 400 ppm EA alone was fed to the animals for one week before FAA exposure and one week after the carcinogen treatment. Animals were killed at intervals up to 20 weeks after cessation of the carcinogen. Liver altered foci and neoplasms were quantified using gamma-glutamyl transpeptidase reaction as well as conventional staining for identification. Exposure to FAA alone induced a substantial number of altered foci and at the end of experiment (week 36), the incidence of hepatocellular neoplasms was 100%. In the group receiving EA together with FAA, the number of altered foci was decreased at all time points and at termination, the final incidence of hepatocellular neoplasms (30%) was also reduced. Thus, EA inhibited the hepatocarcinogenesis induced by FAA when it was administered concurrently with the carcinogen. PMID- 2906932 TI - Serological diversity within the species Legionella spiritensis. AB - A strain of Legionella isolated from the environment which could not initially be identified was shown by restriction fragment length polymorphisms to be a Legionella spiritensis. This was confirmed by DNA homology studies, cell wall fatty acid composition and isoprenoid quinone analysis. This strain, which is only the second reported representative of the species, was shown to be serologically distinct from the type strain of L. spiritensis and all other serogroups of Legionella. PMID- 2906933 TI - Inhibitory effect of DG-5128 on steroid-dependent asthma. AB - To study the possible role of alpha-2 receptors in intractable asthmatics, we investigated the ameliorative effects of 2-[2-(4,5-dihydro-1H-imidazol-2-yl)-1 phenylthyl]pyridine dihydrochloride sesquihydrate (DG-5128) on 10 steroid dependent asthmatic patients. The forced expiratory volume in 1 second (FEV1) and the respiratory resistance (Rrs) were measured 1, 2, and 3 hours after oral administration of 200 mg DG-5128 and compared with the premedication measurements. Two hours after DG-5128 administration, the FEV1 rose significantly (p less than 0.01) and the Rrs decreased significantly (p less than 0.05). Asthmatic symptoms (cough, wheezing, dyspnea) also improved in 80% of the patients. This finding raises the possibility that alpha-2 adrenoceptors exist in human airways, that they play an important role in the pathophysiology of asthma, and that the overfunction of these alpha-2 adrenoceptors and/or Gi-protein cause intractable asthma. PMID- 2906934 TI - Pulmonary involvement in non-specific aorto-arteritis in eastern India. PMID- 2906935 TI - Down-regulation of hepatic LDL receptor protein and messenger RNA in fasted rabbits. AB - Rabbits fasted for 9 and 14 d exhibited 6- and 8-fold increase in plasma cholesterol level, respectively. As one of the mechanisms causing hypercholesterolemia in fasted rabbits, the decreased activity of hepatic low density lipoproteins (LDL) receptor has been reported (Stoudemire, J.B., Renaud, G., Shames, D.M., & Havel, R.J. (1984) J. Lipid Res. 25, 33-39). In order to demonstrate the down-regulation of hepatic LDL receptor on a molecular basis, we carried out immunoblotting of the liver membranes with a specific antibody against LDL receptors and blot hybridization of hepatic RNAs with cDNA of LDL receptor. Immunoblotting showed that LDL receptors in fasted rabbits were markedly decreased, and blot hybridization of RNAs showed a significant decrease in mRNA level of hepatic LDL receptor in fasted rabbits. Further, significant decreases both in LDL binding to liver membrane and in hepatic 3-hydroxy-3 methylglutaryl coenzyme A reductase activity in fasted rabbits were demonstrated. From these results, we concluded that hypercholesterolemia in fasted rabbits is caused by the impaired catabolism of LDL due to down-regulated biosynthesis of hepatic LDL receptor. PMID- 2906936 TI - Complex formation between anionic semiquinoid form of a flavoenzyme D-amino acid oxidase and ligands. Stabilizing mechanism of anionic semiquinoid flavoenzyme. AB - Picolinate binds to the anionic semiquinoid form of D-amino acid oxidase (DAO), and the complex formed has a broad absorption band in the long-wavelength region extending beyond 800 nm, which is reminiscent of a charge transfer interaction. The binding has a stoichiometry of 1:1 with respect to the enzyme. The dissociation constant at 25 degrees C was 30 microM at pH 7.0. The pH dependence (pH 7.0-8.3) of the dissociation constant indicates that one proton is associated with the complex formation, and suggests that picolinate able to bind to the anionic semiquinoid enzyme is in the cationic form protonated at the nitrogen atom. By adding dithionite to the oxidized DAO solution containing pyruvate and various amines, a similar anionic semiquinoid DAO complex having a broad long wavelength absorption band, appeared. Resonance Raman spectra with excitation at 623.8 nm of the anionic semiquinoid DAO complex formed in the presence of pyruvate and methylamine indicate that the complex consists of the anionic semiquinoid DAO and N-methyl-alpha-iminopropionate produced from pyruvate and methylamine, and that the imino group must be protonated. This supports the proposal that the presence of a positively charged group in the vicinity of flavin is required for the stabilization of the anionic semiquinoid flavin. The results also suggest that the broad absorption band is derived from the charge transfer interaction between the anionic semiquinoid flavin and the imino acid, in which the flavin C(4a)-N(5) locus and the locus containing (Formula: see text) of the amino acid are important for the interaction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2906937 TI - Dopamine D2 receptors retain agonist high-affinity form and guanine nucleotide sensitivity after removal of sialic acid. AB - The ligand binding subunit of the D2 dopamine receptor (Mr approximately equal to 94,000) can be visualized by autoradiography following photoaffinity labeling with [125I]N-azidophenethylspiperone and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Following removal of sialic acids with the exoglycosidase, neuraminidase, [125I]N-azidophenethylspiperone photoincorporated into a protein of Mr = 54,000 with the appropriate pharmacological profile for D2 receptors. The desialylated D2 receptor bound dopaminergic agonists with high affinity and was capable of coupling to a functional G-protein as indexed by: 1) pertussis-toxin mediated [32P]ADP ribosylation of proteins of Mr = 42,000 and 39,000, and 2) the conversion of the agonist high affinity form of D2 receptors to one displaying low affinity for agonists in the presence of guanine nucleotides. These data suggest that sialic acid residues do not contribute significantly to the ligand binding characteristics of D2 receptors despite the large change produced in the estimated molecular mass of the binding subunit. PMID- 2906938 TI - Patient knowledge of cardio-respiratory drugs. AB - Eighty-five patients were interviewed to determine their knowledge of their prescribed medicines, the dosing changes they made, the action taken if adverse effects occurred and their information requirements. Most (85%) knew the reason for use of their medicines and many (73%) knew the frequency of use, but few had been told the anticipated duration of use (16%) or been warned of adverse effects (8%). Patients changed the doses of 34% of medicines as they felt appropriate. Forty patients (47%) considered they had experienced side-effects, and 42% of all patients did not disclose their adverse effect. Fifty-eight patients (68%) posed questions about their treatment. These questions concerned efficacy or indication (38%), side-effects (26%), dosing instruction (20%), duration of treatment (18%) and miscellaneous topics (29%). PMID- 2906939 TI - Separation of optical isomers of methoxyphenamine and its metabolites as N heptafluorobutyryl-L-prolyl derivatives by fused-silica capillary gas chromatography. PMID- 2906940 TI - Perfluorinated acids as ion-pairing agents in the determination of monoamine transmitters and some prominent metabolites in rat brain by high-performance liquid chromatography with amperometric detection. AB - The behaviour of trifluoroacetate and heptafluorobutyrate as pairing ions for the reversed-phase ion-pair separation of monoamine transmitters and related metabolites was studied. The performance of systems with the perfluorinated acids was compared with that of systems containing sodium octyl sulphonate and was found to be better in terms of peak resolution combined with total analysis time, day-to-day reproducibility and the time required for attaining initial chromatographic equilibrium. Rat brain samples were deproteinized in the acidified mobile phase, injected directly on to a high-performance liquid chromatographic column and quantitated using an amperometric detector. Sample run times were 6-8 min, at a relatively low flow-rate. The detection limits achieved are fairly uncommon with conventional bore columns. The two perfluorinated acids studied differ in the dominant mechanisms of ion-pair formation and show selectivity differences as a result. PMID- 2906941 TI - Selective effect of clonazepam and (S)-uxepam on the binding of warfarin enantiomers to human serum albumin. AB - Both clonazepam and (S)-uxepam selectively increase the binding of (S)-warfarin to human serum albumin. By liquid affinity chromatography, improved resolution of rac-warfarin was achieved. PMID- 2906942 TI - On-line capillary zone electrophoresis-ion spray tandem mass spectrometry for the determination of dynorphins. AB - Capillary zone electrophoresis-mass spectrometry and capillary zone electrophoresis-tandem mass spectrometry with ionization at atmospheric pressure are demonstrated as being feasible for the separation and determination of small peptides such as dynorphins (1-6, 1-7, 1-8, 1-9) and leucine enkephalin at low picomole levels by full-scan mass spectrometry and tandem mass spectrometry and at the low femtomole range under selected ion monitoring conditions. Ion evaporation resulting from the ion spray liquid chromatography-mass spectrometry interface exhibits primarily molecular weight information as singly and multiply charged ions and is shown to be a sensitive and mild ionization method for peptides. The full-scan daughter ion mass spectrum of leucine enkephalin is shown to contain fragment ions consistent with the sequence of the peptide. Parent ion scanning in the tandem mass spectrometry mode is a promising technique for the screening of related peptides. PMID- 2906944 TI - Agoraphobics' understanding of the development and maintenance of their symptoms. AB - A 24-item test was devised to study the degree of understanding a group of agoraphobics had of the etiology and behavioral treatment of their symptoms before and after treatment, whether understanding was related to mode of symptom acquisition and, finally, if increase in understanding was related to treatment outcome. Clients were found to be ill-informed in areas most directly related to realistic exposure strategies, but there was no difference between those who had conditioning as opposed to cognitive acquisition histories. Changes in understanding were found to be related to outcome measures. PMID- 2906943 TI - Biotinylated DNA probes for exotoxin A and pilin genes in the differentiation of Pseudomonas aeruginosa strains. AB - Biotin-labeled DNA probes derived from Pseudomonas aeruginosa exotoxin A and pilin genes were tested for their ability to distinguish strains among a selected group of P. aeruginosa isolates. Probing of Southern blots of restriction digests of DNA from test strains with the exotoxin A probe demonstrated a unique hybridization pattern for each independently isolated strain containing the exotoxin A gene. Two phenotypically distinct strains isolated from the same patient were found to be identical in their DNA hybridization patterns. By using a pilin gene probe, similar distinction was made between independent strains, while strains from the same source were confirmed to be identical. Furthermore, DNA from a strain of P. aeruginosa lacking the exotoxin A gene yielded a unique pattern of restriction fragments which hybridized to the pilin gene probe. The exotoxin A and the pilin probes may together prove to be useful tools in epidemiological surveys during outbreaks of P. aeruginosa infection. PMID- 2906945 TI - In vivo desensitization in the treatment of recurrent nightmares. AB - The literature, although sparse, suggests that behavioral interventions targeting the overt waking manifestations of the fear content of nightmares, can effectively reduce the frequency and intensity of these dreams. A 20-year-old female with recurrent nightmares centering on a fear of snakes, was treated by in vivo desensitization in which she approached a live, harmless snake. During treatment the client displayed habituation of fear of the snake and this corresponded to reductions in her nightmares. By the end of treatment and at 3 month and 1-year follow-up evaluations, she was free of fear and her nightmares had been eliminated. It is suggested that in vivo behavioral treatment of the content of nightmares may be a very effective way to eliminate these distressing dreams. PMID- 2906946 TI - A multifaceted behavioral intervention for pill-taking avoidance associated with Tylenol poisoning. AB - The effectiveness of relaxation training, imaginal exposure and in vivo exposure to pills in the treatment of pill-taking avoidance resulting from a fear of poisoning associated with Tylenol was investigated. Following relaxation training and imaginal exposure to vitamin consumption, one session of in vivo exposure to vitamin taking resulted in daily vitamin use. One session of in vivo exposure to aspirin and placebo capsules (substitutes for prescribed medication) resulted in consumption of aspirin as needed and daily ingestion of placebo pills. Interestingly, treatment effects generalized to leftovers and wine, two related phobic stimuli, without additional intervention. At three and six month follow up, the subject reported maintenance of treatment effects. Psychophysiological assessment data were consistent with the subject's self-report. PMID- 2906947 TI - Beta-adrenergic antagonists in psychosis: is improvement due to treatment of neuroleptic-induced akathisia? AB - Van Putten and colleagues have reported an association between akathisia and exacerbations of psychosis in schizophrenic patients treated with neuroleptic drugs. They noted that treatment with an anticholinergic drug, biperiden, led to prompt improvement in both conditions. Recent reports suggest that beta adrenergic antagonists may be effective in the treatment of akathisia. Based on these observations, we surveyed studies in which beta-adrenergic antagonists were administered as putative antipsychotic agents in order to determine whether reports of improvement may actually have reflected successful treatment of underlying neuroleptic-induced akathisia. Though inferential, the results of this review support this hypothesis. It is possible that the mechanism of action for the anti-akathisia and antipsychotic effects of beta-adrenergic antagonists may be due to enhancement of the firing rate of dopamine neurons in the ventral tegmental area, with subsequent increased release of dopamine and decreased interference with dopaminergic neurotransmission. PMID- 2906948 TI - Psychotic patients who become worse on neuroleptics. AB - We describe a group of psychotic patients who became worse early in the course of neuroleptic treatment. Characteristics of this group were: predominantly female sex, relatively brief onset, family history of affective disorder, hypomotoric presentation, and severe neuroleptic side effects. We propose that some patients with affective psychoses are uniquely susceptible to profound blockade of the nigrostriatal dopaminergic system by neuroleptics. PMID- 2906949 TI - View from the Nation's Courts. PMID- 2906950 TI - Screening of Israeli Holstein-Friesian cattle for restriction fragment length polymorphisms using homologous and heterologous deoxyribonucleic acid probes. AB - Genomic DNA of Israeli Holstein-Friesian dairy cattle were screened with a battery of 17 cloned or subcloned DNA probes in an attempt to document restriction fragment length polymorphisms at a number of genetic loci. Restriction fragment length polymorphisms were observed at the chymosin, oxytocin neurophysin I, lutropin beta, keratin III, keratin VI, keratin VII, prolactin, and dihydrofolate reductase loci. Use of certain genomic DNA fragments as probes produced hybridization patterns indicative of satellite DNA at the respective loci. Means for distinguishing hybridizations to coding sequences for unique genes from those to satellite DNA were developed. Results of this study are discussed in terms of strategy for the systematic development of large numbers of bovine genomic polymorphisms. PMID- 2906951 TI - Neuropeptide Y-, tyrosine hydroxylase- and vasoactive intestinal polypeptide immunoreactive nerves in bone and surrounding tissues. AB - Nerve fibres immunoreactive to neuropeptide Y (NPY), tyrosine hydroxylase (TH) and vasoactive intestinal polypeptide (VIP) were demonstrated in rat bone and adjacent tissues. The distribution of NPY- and TH-positive fibres differed from that of VIP-positive fibres. NPY- and TH-immunoreactive fibres were almost exclusively found close to or within the blood vessel walls, mostly in the vicinity of the epiphyseal plate, but also in the Volkmann canals. VIP-positive fibres were predominantly present in the epiphysis and periosteum and only occasionally around blood vessels. This study demonstrates that bone and surrounding tissues have a supply of both noradrenergic and peptide-containing nerves. The differential distribution of these nerves may reflect specific roles in the local regulation of bone physiology, such as blood flow, bone formation or resorption. PMID- 2906952 TI - Putative neurotransmitters involved in medullary cardiovascular regulation. AB - Experiments were carried out in artificially ventilated pentobarbital anesthetized male Wistar rats. Following microinjection of muscimol (GABA mimetic) or kynurenic acid (KYN; glutamate antagonist) into the ventrolateral medullary depressor area (VLDA), microinjection of L-glutamate (GLU; 4.5 nmol) into the NTS elicited a pressor response. This pressor response was attenuated in a dose-dependent manner by microinjection of KYN (0.5-5 nmol) into the ventrolateral medullary pressor area (VLPA). A GLU-induced pressor response could also be elicited from the NTS when GABA receptors in the VLPA were blocked with the microinjection of bicuculline (GABA antagonist, 200 pmol) into this site. The same dose of bicuculline in the VLPA also blocked the depressor responses elicited from the VLDA. With the VLDA or VLPA functionally unimpaired, microinjection of GLU (4.5 nmol) into the NTS elicited a fall in blood pressure and heart rate. This depressor response was attenuated in a dose-dependent manner by the microinjections of KYN (2-20 nmol) into the VLDA. These results indicate that: (1) The NTS sends glutamatergic inputs to both the VLDA and the VLPA; the projection from the NTS to the VLPA mediates pressor responses while that from the NTS to the VLDA represents one component of the pathway mediating the depressor responses elicited from the NTS. (2) The pathway from the VLDA to the VLPA is GABA-ergic and represents another component of the pathway mediating depressor responses evoked from the NTS. (3) The bradycardia evoked from the NTS may involve a pathway from the NTS to the VLDA. PMID- 2906954 TI - Observations on feeding potential of some indigenous fishes on mosquito larvae in Nilgiri Hills, Tamil Nadu. PMID- 2906953 TI - Effects of acute and chronic beta-adrenoceptor blockade on baroreflex sensitivity in humans. AB - To determine whether beta-adrenoceptor blockade lowers blood pressure by potentiating arterial baroreflex sensitivity (BRS), we compared the effect of acute i.v. and chronic oral beta-blockade on the BRS (phenylephrine technique) of 51 subjects with essential hypertension. Subjects were randomly assigned in a double-blind protocol to one of atenolol, metoprolol, pindolol or propranolol. There was an increase in BRS, unrelated to changes in heart rate, after both acute and chronic beta-blockade. This effect was most evident in younger and less hypertensive subjects. Decreases in blood pressure after 5-months' treatment were unrelated to increases in BRS, indicating that the hypotensive action of these drugs is not dependent upon augmented baroreflex control of heart rate. Only propranolol, of the 4 beta-blockers, increased BRS significantly after acute and chronic treatment. The acute effect of propranolol was significantly different from that of i.v. metoprolol (P less than 0.008) but the effect of long-term treatment with propanolol was not significantly different from that of the other 3 beta-blockers. We conclude that the impaired reflex regulation of heart rate can be improved in younger and mild-to-moderate hypertensive patients by beta adrenoceptor blockade. Further studies, involving larger numbers and perhaps fewer drugs are needed to determine the relative importance of lipophilicity and beta 1- or beta 2-receptor selectivity in mediating the increase in baroreflex sensitivity seen with treatment. PMID- 2906955 TI - Lithium and renal function in relation to concomitant theory. AB - Two hundred and fourteen patients (99 men, 115 women, age 21-87 years) were treated with lithium during the period 1963-1984 at the Psychiatric Unit, Danderyd Hospital. The patients were diagnosed as having bipolar depression (97), unipolar depression (54), cycloid psychosis (21), schizoaffective psychosis and depressive neurosis (42). Sixty patients were treated with lithium salt only, 73 patients received neuroleptic drugs in addition to lithium and 51 antidepressant drugs. Sixteen patients were treated with a combination of neuroleptic drugs, antidepressant drugs and lithium. Fourteen patients were treated with lithium and benzodiazepines. The aim of this retrospective lithium study was to examine the renal function in these different treatment groups. The results show that patients treated with a lithium salt and neuroleptic drugs have significantly lower urinary osmolality than those treated with a lithium salt only. Also tricyclic antidepressants in combination with a lithium salt appear to have an influence on renal function. The duration of concomitant therapy seems to be of importance for the effect on renal function. Eleven patients with the lowest osmolality values were investigated at the Renal Unit, Danderyd Hospital, but in no case was it necessary to withdraw the lithium treatment. PMID- 2906956 TI - Sympathetic (alpha-beta) or calcium channel blockade for hypertensive myocardial infarction? A haemodynamic comparison of labetalol and nifedipine. AB - The haemodynamic impact of alpha- and beta-adrenoceptor blockade (labetalol) was compared with that of slow-calcium channel blockade (nifedipine) in 32 patients with sustained elevation of systemic arterial pressure (systolic blood pressure greater than 160; diastolic blood pressure greater than 95 mmHg) following a recent myocardial infarction (6-22 h). Patients with normal (pulmonary artery occluded pressure; (PAOP less than 18 mmHg; n = 16) or impaired (PAOP greater than 18 mmHg; n = 16) left ventricular function were randomized to labetalol (1 mg/kg i.v. 15 min) or nifedipine (20 mg sublingually) and haemodynamic profile was measured over 2 h. Both drugs equally reduced mean systemic arterial pressure (P less than 0.01 versus pretreatment control), and presumably left ventricular afterload; however, the heart rate (P less than 0.01) and cardiac index (P less than 0.01) increased after nifedipine, contrasting with reductions in both variables following labetalol (P less than 0.01). The elevated left ventricular filling pressure was reduced by both labetalol (P less than 0.05) and nifedipine (P less than 0.01) but the reduction was greater following nifedipine (-2 mmHg versus -5 mmHg, P less than 0.05). Thus both compounds were equally effective hypotensive agents. Labetalol consistently reduced cardiac stroke work and double product, important determinants of myocardial oxygen requirements; however, nifedipine afforded some improvement in cardiac performance in patients with left ventricular dysfunction. PMID- 2906957 TI - Mlsa determinants: relationship to Fc gamma receptor and tissue distribution. AB - We have analysed the genetic relationship between Mlsa and Fc gamma R in mice. Using the Fc gamma R-specific DNA probes, we were unable to detect a restriction fragment length polymorphism (RFLP) which is consistent in DNA derived from Mlsa strains and which differed from that of Mlsb strains, while we could see a polymorphism that distinguishes Ly17.1 from Ly17.2, alleles of the Fc gamma R. These results strongly suggest that Mlsa is neither a product of the alpha Fc gamma R nor of the beta Fc gamma R gene. Furthermore, we have re-examined the tissue distribution of Mlsa determinants using a major histocompatibility complex (MHC) class II antigen-positive T-cell tumour as well as a pure population of bone marrow derived macrophages of Mlsa genotype. Both these cell types were recognized to varying degrees by alloreactive cells; however, none of them expressed functionally detectable Mlsa determinants. We conclude from our studies that Mlsa is a highly stimulatory self peptide that is exclusively expressed in B cells. PMID- 2906958 TI - Mucosal T cell networks: role of Fc alpha R+ T cells and Ig BF alpha in the regulation of the IgA response. PMID- 2906959 TI - Mechanisms by which tumor necrosis factor stimulates hepatic fatty acid synthesis in vivo. AB - We have previously shown that bolus intravenous administration of tumor necrosis factor (TNF) to normal rats results in a rapid (within 90 min) stimulation of hepatic fatty acid synthesis, which is sustained for 17 hr. We now demonstrate that TNF stimulates fatty acid synthesis by several mechanisms. Fatty acid synthetase and acetyl-CoA carboxylase (measured after maximal stimulation by citrate) were not higher in livers from animals that had been treated with TNF 90 min before study compared to controls. In contrast, 16 hr after treatment with TNF, fatty acid synthetase was slightly elevated (35%) while acetyl-CoA carboxylase was increased by 58%. To explain the early rise in the hepatic synthesis of fatty acids, we examined the regulation of acetyl-CoA carboxylase. The acute increase in fatty acid synthesis was not due to activation of acetyl CoA carboxylase by change in its phosphorylation state (as calculated by the ratio of activity in the absence and presence of 2 mM citrate). However, hepatic levels of citrate, an allosteric activator of acetyl-CoA carboxylase, were significantly elevated (51%) within 90 min of TNF treatment. TNF also induces an acute increase (within 90 min) in the plasma levels of free fatty acids. However, hepatic levels of fatty acyl-CoA, which can inhibit acetyl-CoA carboxylase, did not rise 90 min following TNF treatment and were 35% lower than in control livers by 16 hr after TNF. These data suggest that TNF acutely regulates hepatic fatty acid synthesis in vivo by raising hepatic levels of citrate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2906960 TI - Seasonal activity of mosquitoes in an Ockelbo disease endemic area in central Sweden. AB - In the Sassman area, province of Halsingland, Sweden, mosquitoes were sampled in 1983 from aquatic habitats, overwintering sites, cattle sheds, human bait, with UV-light traps, rabbit-, guinea-pig-, hen-, dove- and unbaited suction traps and similarly baited net traps. Anopheles beklemishevi, An. messeae, Aedes cantans, Ae. cataphylla, Ae. cinereus, Ae. communis, Ae. diantaeus, Ae. excrucians, Ae. hexodontus, Ae. intrudens, Ae. leucomelas, Ae. pionips, Ae. punctor, Ae. vexans, Culex pipiens, Cx. torrentium, Cx. territans, Culiseta alaskaensis, Cs. bergrothi, Cs. morsitans, Cs. ochroptera and Mansonia richiardii were recorded as new to the province. Data are presented on the ecology including seasonal abundance and seasonal blood-feeding activity of each species. Ockelbo disease, caused by a virus indistinguishable from Sindbis virus, is prevalent amongst humans in the study area. The ecological and behavioral potential of species of Culex, Culiseta and Aedes to transmit the virus is discussed. PMID- 2906961 TI - Occurrence of Psorophora columbiae eggs in different field types comprising a Texas riceland agroecosystem. AB - Soil samples (3,258) were collected from soybean fields, rice fields and permanent pastures in Chambers County, TX over a 2 1/2-year period and examined for the presence of Psorophora columbiae eggs. Eggs occurred more frequently and in greater numbers in samples taken from soybean fields than in samples from either rice fields or permanent pastures during the summers of 1979 and 1981 when there was heavy rainfall in the study area. Under dry conditions, as during the summer of 1980, the frequency of egg occurrence and abundance increased in samples taken from rice fields. However, egg occurrence and abundance in soybean field samples still remained relatively high even during this particular year. PMID- 2906962 TI - Evaluation of two new insect growth regulators against mosquitoes in the laboratory. AB - Biological activity of two new IGRs was studied under laboratory conditions against 2nd- and 4th-instar larvae and pupae of Anopheles quadrimaculatus, Aedes aegypti and Culex tarsalis. The IGR S-21149, an oxime [0-(2-(4' Phenoxyphenoxy)ethyl propionaldoxime], produced an overall mortality or inhibition of emergence of 95% (when 4th instar treated) at 0.0047, 0.0013 and 0.00041 mg/liter in the three species, respectively. The EI95 values for the second IGR S-31183, a pyridine compound, [1-(4'-Phenoxyphenoxy)-2-(2'pyridyloxy) propane] were 0.017, 0.0026 and 0.00032 mg/liter for the three species, respectively. Both materials in general were less active against 2nd than 4th instar larvae, except that the 2nd- and 4th instars of An. quadrimaculatus were equally susceptible. Pupae treated at up to 0.1 mg/liter showed no mortality in the pupal or the ensuing adult stages. PMID- 2906963 TI - Effectiveness of soap formulations containing deet and permethrin as personal protection against outdoor mosquitoes in Malaysia. AB - Two soap formulations, both containing 20% deet and one each containing permethrin at 0.5 and 1.0%, respectively, were applied to exposed arms and legs of volunteers as personal protection against outdoor human biting mosquitoes in six locations on Penang Island, Malaysia. The predominant mosquito species collected from these locations were Aedes albopictus, Mansonia uniformis, Culex gelidus, Anopheles lesteri and Armigeres subalbatus. Efficacy and residual effects up to 4 hours indicated good protection against these species. Reduction in mosquito landing-biting rates in treated groups ranged from 83.8 to 100.0%. At high densities, small percentages of Ma. uniformis and An. lesteri landed or bit on treated skin. Use of the soap formulations in terms of cost-effectiveness, safety and overall vector control strategy for some tropical diseases is discussed. PMID- 2906964 TI - Use of an exterior curtain-net to evaluate insecticide/mosquito behavior in houses. PMID- 2906965 TI - Insecticide resistance in mosquitoes: a pragmatic review. AB - Descriptions of the World Health Organization standard methods of assessing susceptibility or resistance in larval and in adult mosquitoes are presented, and the evaluation of their results are discussed. Other susceptibility test methods are also mentioned, including those based on esterase zymograms. Recent work on the biochemical mechanisms of resistance and cross-resistance are reviewed, along with possible countermeasures for the problem of mosquito resistance, now known in 113 species of culicines and anophelines. PMID- 2906966 TI - Determination and significance of suspended protein in wastewater. AB - A simple method is presented to measure the nutrient load of wastewater. Suspended particles, including microorganisms, are collected on a membrane filter by vacuum filtration, followed by colorimetric protein assay. Soluble proteins can be determined in the filtrate by precipitation. In domestic sewage and agricultural dairy wastewater, the largest portion of protein was retained on the membrane. Young larvae of Culex nigripalpus, Cx. quinquefasciatus and Aedes aegypti pupated when maintained in wastewater or its sediment but not when maintained in a membrane filtrate. If mosquito larvae feed primarily on suspended particles, the assay can be used to identify major feeding areas and may result in more economic application of microbial larvicides that act as food poisons. PMID- 2906967 TI - Differences between the nutritional reserves of laboratory-maintained and field collected adult mosquitoes. AB - Individual female mosquitoes from field populations of Aedes aegypti, Culex nigripalpus and Coquillettidia perturbans were analyzed for sugar, glycogen and lipids. Controls were maintained in the laboratory for 7 to 10 days on 2% and either 10 or 20% sucrose. Mosquitoes held in the laboratory had significantly more glycogen and lipid than field-collected mosquitoes of the same species. Laboratory mosquitoes maintained on 10 or 20% sucrose contained more sugar than did field mosquitoes. Mosquitoes of the above species were collected at field sites in January, April, July and October and nutritional reserves were determined. Seasonal differences in reserves were documented in females of all species. However, even when reserves were at their highest in field-collected mosquitoes they rarely approached the reserves in mosquitoes of the same species maintained in the laboratory on 10 or 20% sucrose. Since laboratory-maintained mosquitoes are nutritionally different from those in the field, results of laboratory studies on flight performance, host attractancy, biting, disease transmission and oviposition behavior may be biased. PMID- 2906968 TI - Vector potential of culicine mosquitoes in Faiyum Governorate, Egypt. AB - Culicine mosquito populations were studied for 1 year in 2 neighboring villages in Faiyum Governorate, Egypt. Dominant species in larval collections included Culex pipiens, Cx. univitattus, Cx. antennatus, Aedes caspius and Uranotaenia unguiculata; Culiseta longiareolata was less common. Culex pipiens accounted for 98% of 3,743 mosquitoes captured in human-biting collection (164 man-nights), 96% of 1,136 mosquitoes collected inside houses and animal sheds (396 inspections), and 98% of 15,000 mosquitoes from 22 donkey-baited traps. Adult Cx. univittatus, Cx. antennatus and Ae. caspius were infrequently captured by any of the collection techniques. Although larval collections identified 5 common species, only Cx. pipiens showed a significant association with the human population. PMID- 2906969 TI - Occurrence and seasonal incidence of mosquitoes on Indian reservations in Iowa, Nebraska and South Dakota during 1983. AB - A mosquito surveillance program designed to prevent future human cases of Western equine encephalitis or Saint Louis encephalitis was established in 1983 on Indian reservations under the jurisdiction of the Aberdeen Area Indian Health Service in Iowa, Nebraska and South Dakota. Standard New Jersey light traps were operated on all reservations throughout the summer season while CDC miniature and encephalitis virus surveillance traps were employed for shorter periods of time on 4 reservations. Aedes vexans was the most abundant species except on the Pine Ridge, Rosebud, Winnebago and Yankton Sioux reservations in which Culex tarsalis predominated and for the Sac-n-Fox where Aedes trivittatus occurred with the greatest frequency. PMID- 2906970 TI - Timing of pupal-adult apolysis in mosquitoes. PMID- 2906971 TI - Presumed Dirofilaria immitis infections from field-collected mosquitoes in North Carolina. PMID- 2906972 TI - An automatic carbon dioxide delivery system for mosquito light trap surveys. PMID- 2906973 TI - Susceptibility of three species of mosquitoes to a Pasteur Institute preparation of Bacillus sphaericus (strain 2297). PMID- 2906974 TI - Bases of mosquito systematics. PMID- 2906975 TI - Growth of three mosquitoes on two larval diets measured by protein accumulation. AB - Larval growth recorded as accumulation of protein was measured in Aedes aegypti, Culex nigripalpus and Culex quinquefasciatus, raised on liver powder or dry brewer's yeast. In the early stages all 3 species grew faster on liver powder, but at pupation there was no significant difference in protein content between diets and among species. Aedes aegypti pupated one day ahead of Culex. PMID- 2906976 TI - Changes in local mosquito fauna following beaver (Castor canadensis) activity. AB - A marked decrease in anthropophilic temporary water mosquito populations subsequent to impoundment of extensive areas of larval development by beavers is documented. Absence to date of development of other mosquito species in the permanent water thus established is noted and discussed relative to current characteristics of the site. PMID- 2906978 TI - A more accurate method for assessment of Psorophora columbiae larvicidal tests. PMID- 2906977 TI - Evaluation of new insect growth regulators against mosquitoes with notes on nontarget organisms. AB - Three new insect growth regulators (IGRs) were tested against Culex, Aedes and Psorophora mosquitoes. In the laboratory the 3 IGRs were active in the range of 0.3 to 1.5 ppb against Cx. quinquefasciatus. In field tests, the IGRs fenoxycarb and S-31183 formulations yielded complete control of floodwater mosquitoes at the rates of 0.005 to 0.01 lb AI/acre. In field tests against Cx. tarsalis, S-31183 formulations produced complete inhibition of emergence at the rates of 0.005 to 0.025 lb AI/acre. Fenoxycarb formulation produced similar results at the rate of 0.1 lb AI/acre. It is possible that initial and residual field activity of both IGRs can be increased by employing suitable formulations. PMID- 2906979 TI - Description of a baited trap for sampling mosquitoes. PMID- 2906980 TI - Observations on the effect of cyromazine on inhibition of larval mosquito development in diluted wastewater. PMID- 2906981 TI - Failure of mosquitoes to colonize teasel axils in Illinois. PMID- 2906982 TI - The use of mepacrine hydrochloride to control Vorticella on mosquito larvae. PMID- 2906983 TI - Changing patterns in mosquito-borne arboviruses. AB - Research leading to the current state of knowledge on the epidemiology of La Crosse virus (LACV), Jamestown Canyon virus (JCV) and dengue (DEN) viruses is summarized in relation to the generally recognized criteria for incriminating vectors. The importance of vector biology and local ecological conditions is emphasized as is the necessity of a good balance between laboratory and field based studies. The influence of human activity in shaping the epidemiological patterns of all three of these arboviruses is readily apparent. PMID- 2906984 TI - Combination ground and aerial adulticide applications against mosquitoes in an Arkansas riceland community. AB - Simultaneous ground and aerial adulticide applications were evaluated against riceland mosquitoes in Stuttgart, AR, during July 1985. Naled was aerially applied at 52.6 ml/ha over 10.4 km2 surrounding the city. Ground ULV applications of a mixture of malathion, HAN and resmethrin/PBO (1:1:0.0625) were applied within the city at a rate of 221.8 ml/min at 24 kph. Adult populations of Anopheles quadrimaculatus and Psorophora columbiae were reduced at 24 hr but resurgence of Ps. columbiae was evident at 48 hr posttreatment. Posttreatment data indicated that movement of both mosquitoes occurred along the path of prevailing wind. PMID- 2906985 TI - Comparative studies of Metarhizium anisopliae and Tolypocladium cylindrosporum as pathogens of mosquito larvae. AB - Mosquito fungal pathogens, Metarhizium anisopliae and Tolypocladium cylindrosporum, were compared with regard to virulence against the larvae of Aedes aegypti, Anopheles stephensi and Culex pipiens. Culex pipiens larvae were much more susceptible to M. anisopliae conidia than An. stephensi or Ae. aegypti. But Ae. aegypti and Cx. pipiens larvae were equally susceptible to T. cylindrosporum propagules which weakly attack An. stephensi. Using a high concentration conidial suspension (10(7) sp/ml) of M. anisopliae no. 139, Ae. aegypti larvae were killed immediately within 1.1 days, before intrahemocoelian invasion; but at lower concentrations (10(6) and 10(5) sp/ml), typical mycosis occurred. However, T. cylindrosporum no. 3 blastospores were much more pathogenic to Ae. aegypti larvae than conidia. Conidial suspension of 10(7) spores/ml killed 68% fourth-instar larvae, relative to the 96% invaded by blastospores under the same conditions. Presoaked conidia virulence appeared still intermediate between conidia and blastospores. At low temperatures, 15 degrees C, virulence of M. anisopliae highly decreased, while at the same temperature, T. cylindrosporum blastospores were still virulent. PMID- 2906986 TI - Temporal abundance and percent insemination of newly-emerged adult female Psorophora columbiae near the larval habitat. AB - The temporal abundance and percent insemination of newly-emerged adult female Psorophora columbiae were investigated in riceland sites near Anahuac, TX. Pre- and postmating nights were characterized by low numbers of females and little mating activity (no significant increase in percent insemination) occurring in the study site. Mating nights were characterized by high female abundance in the study site before sunset then steadily decreased until a stable, low level of abundance was reached approximately 2 to 2.5 hr after sunset. On mating nights, percent insemination of female mosquitoes in the study site remained low until sunset, after which it steadily increased until a maximum was reached about 2 hr after sunset. On each mating night, approximately 2 to 2.5 hr after sunset, a mass exodus from the site by primarily mated females with some males was observed. PMID- 2906987 TI - Effects of sound on swarming male Psorophora columbiae. AB - Male Psorophora columbiae were shown to respond to sound during swarming. The responses consisted of abrupt changes in flight speed and direction. Tones with frequencies of 200 to 425 Hz were attractive to males over a distance of at least 1 m. Male mosquitoes responded better to tones with sine waveforms than they did either to square waveforms or triangular waveforms. Swarming males became accommodated and no longer responded to sounds presented for 5 seconds or longer. Based on observations of field populations of swarming Ps. columbiae, it appears that males use sound waves to locate females, but additional factors seem to be required for males to initiate the actual copulatory behavior. Also, males appear to use sound to maintain their position and spatial relationship within the swarm. PMID- 2906988 TI - Distribution of mosquitoes in different wastewater stages of secondarily treated domestic effluent and untreated citrus washwater. AB - In Indian River County, Florida, mosquito populations were monitored weekly for 12 months in early and more advanced treatment stages of secondarily treated domestic wastewater and also in untreated primary and secondary citrus packing house washwater. Well defined differences in mosquito species abundances for early vs. late wastewater stages existed. In the early levels of secondarily treated effluent and in the primary citrus washwater, Culex quinquefasciatus populations were dominant. In the later wastewater stages of both systems, Cx. nigripalpus, Anopheles spp. and Uranotaenia spp. were more common. Seasonal Culex spp. abundance patterns were apparent at some but not all study sites. Water chemistry measurements demonstrated that both systems contained relatively low levels of nutrient-related parameters with large concentration variability. PMID- 2906989 TI - Identification of Aedes campestris from New Mexico: with notes on the isolation of western equine encephalitis and other arboviruses. AB - An arbovirus survey was conducted during August 1985 at White Sands Missile Range in southcentral New Mexico following a suspected arboviral disease epizootic among feral horses. A total of 20,566 mosquitoes (18,505 females and 2,061 males) and 8,900 biting gnats were collected and assayed for virus. Female mosquitoes were principally Aedes campestris (54.8%), Aedes dorsalis (30.4%) and Culex tarsalis (13.2%). Arboviruses were not isolated from biting gnats, but mosquitoes yielded a total of 37 viral isolates, including western equine encephalitis (WEE) (18), California serogroup (15), Cache Valey (1), and Hart Park (1) viruses in addition to 2, as yet unidentified, rhabdoviruses. Isolates of WEE virus were from 9 pools of Ae. campestris, 6 of Cx. tarsalis and 3 of Ae. dorsalis. California serogroup viruses, including 2 subtypes, were obtained from 7 pools of females and 1 pool of males of Ae. campestris and from 4 pools of Ae. dorsalis. Cache Valley and Hart Park viruses were isolated from single pools of Ae. dorsalis and Cx. tarsalis, respectively, and the rhabdoviruses were obtained from Ae. campestris and Psorophora signipennis. PMID- 2906990 TI - Backyard mosquito larval habitat availability and use as influenced by census tract determined resident income levels. AB - One hundred and eighty premises in each of three distinct economic income levels within the urbanized area of East Baton Rouge Parish, Louisiana were inspected for artificial containers producing mosquitoes. Census tracts, and their accompanying descriptive statistics were used to objectively quantify each of the income levels studied. Differences, presumably due to living conditions associated with income level, were found for the amount, type and condition of the containers encountered in each area, as well as between species composition and the extent of production. Overall, low income areas produced more mosquitoes than either of the other two areas, mainly as a result of the types of containers present. PMID- 2906991 TI - Laboratory colonization and life cycle of Coquillettidia crassipes in Malaysia. AB - Methods are described for the laboratory colonization of Coquillettidia crassipes. The highest rate of insemination occurred in 60 x 60 x 120 cm cages and better insemination in laboratory adapted F15 generation. Embryonation and hatchability of eggs ranged from 69.6 to 97.9% and 63.3 to 94.3% respectively. Gravid females laid egg rafts on water in 500 ml breakers with small leaves of Salvinia for resting. Newly hatched larvae were set up in a basal medium of guinea pig dung and water or liver powder, yeast powder and water. Larvae attached to aquatic plants or 'Keaykolour' ruffia snow white paper. The cultures with paper gave better yields. At present 21 generations of Cq. crassipes have been reared in the laboratory. PMID- 2906993 TI - Toxorhynchites rutilus septentrionalis feeding on tree sap. PMID- 2906992 TI - Mosquitoes attacking dogs in Knox County, Tennessee. PMID- 2906994 TI - Collection of Psorophora howardii in Scott County, Iowa. PMID- 2906995 TI - Voltage-dependent currents prolong single-axon postsynaptic potentials in layer III pyramidal neurons in rat neocortical slices. AB - 1. Using isolated slices of rat cingulate and sensorimotor cortex, intracellular recordings were obtained from pyramidal neurons in layer III. Simultaneous extracellular recordings were obtained from neurons in ventral layer III and layer IV. Spike-triggered averaging was employed to investigate synaptic connections from neurons in layers III/IV to pyramidal cells in layer III. 2. Of 701 simultaneously recorded pairs of neurons, comprising 699 extracellularly and 128 intracellularly recorded neurons, synaptic connections were demonstrated in 30 pairs. Of these, 29 were excitatory postsynaptic potentials (EPSPs) and 1, an inhibitory postsynaptic potential (IPSP). Single-axon EPSPs with a wide variety of amplitudes were recorded: the range recorded at membrane potentials between 68 and -72 mV was 0.079-2.3 mV. Comparing recordings obtained from different cells, EPSP amplitude was found to be independent of both the membrane resistance of the postsynaptic neuron and the EPSP time course; i.e., the largest EPSPs were not necessarily those recorded from neurons with the highest input resistance, nor those with the briefest time course. 3. Shape indices: width at half amplitude and rise-time, indicative of both proximal and distal synaptic locations were obtained. Normalized rise-times were between 0.1 and 2 times the membrane time constant and half-widths between 0.8 and 20 times. 4. The majority of postsynaptic neurons displayed nonlinear voltage relations typical of pyramidal neurons, and the contribution to EPSP shape of voltage-dependent currents was investigated. EPSP amplitude and duration were found to be dependent on membrane potential. The majority of single-axon EPSPs (26 of 29), increased in amplitude and duration with membrane depolarization over the range -95 - -50 mV, despite the significant decrease in driving force for the EPSP that would be expected to accompany such large depolarizations. This increase coincided with an increase in the amplitude of voltage responses to small injected current pulses. 5. It is concluded that the amplitude and time course of single-axon EPSPs recorded in cortical pyramidal somata are affected not only by the amplitude of the postsynaptic current and the location(s) of the synapse(s) relative to the soma, but also by voltage-dependent currents. The possibility that the increase in amplitude and duration of these EPSPs with membrane depolarization is due to N methyl-D-aspartate receptor involvement is discussed. PMID- 2906996 TI - Dipeptidylpeptidase IV--inactivation with N-peptidyl-O-aroyl hydroxylamines. AB - Eleven N-peptidyl-O-aroyl hydroxylamines have been synthesized and their hydrolytic stability, acidity and properties during reaction with dipeptidyl peptidase IV (E.C. 3.4.14.5) investigated. N-peptidyl-O-(4-nitrobenzoyl) hydroxylamines act as irreversible inhibitors of serine proteases. The serine enzyme, dipeptidyl peptidase IV (DP IV), is inactivated by substrate analog derivatives of this class by a suicide inactivation mechanism. During the enzyme reaction of DP IV with the suicide substrates most molecules are hydrolyzed but some irreversibly inactivate the target enzyme. In contrast to porcine pancreatic elastase and thermitase, DP IV exhibits a high ratio for hydrolysis of the compounds versus inhibition during their interaction with the enzyme. Variation of the leaving aroyl residue lowers this ratio. Variation of the substrate analog peptide moieties of the DP IV-inhibitors increases their ability to inhibit the enzyme to a remarkable extent. Possible reaction pathways are discussed. PMID- 2906997 TI - Synaptic organization of the globus pallidus. AB - The synaptic organization of the globus pallidus is reviewed with respect to present knowledge about neurons, fibers, axon terminals, and their intrinsic synaptic relationships. Information derived from studies employing Nissl stains, Golgi impregnations, lesion degeneration techniques, immunohistochemistry, and anterograde axonal labeling in various species are presented along with ultrastructural data. Studies indicate that the globus pallidus contains a principal efferent neuron with smooth or spiny dendrites and simple or complex terminal dendritic arborizations. This cell type receives convergent inputs from intrinsic and extrinsic sources and uses gamma-aminobutyric acid as a transmitter. A smaller and separate population of pallidal projection neurons contains acetylcholine. Two other less frequent neuronal types, of small and medium size, have also been recognized. Three to six types of axonal boutons forming synaptic contacts with pallidal neurons have been recognized in various studies. Among these, three types (types I, II, and III) are the most prevalent. Studies indicate that the most frequent category (type I) originates from neostriatal neurons via radial fiber projections and contains immunoreactive GABA and enkephalins. The synaptic architecture of the globus pallidus is dominated by a mosaic-like arrangement of long dendrites that are ensheathed by longitudinally oriented axons making synapses en passant. Triadic synapses involving dendrites that are pre- and postsynaptic are encountered infrequently. Because both striatopallidal and pallidothalamic connections are inhibitory, pallidal target neurons in the thalamus may be "disinhibited" when the neostriatum is activated. PMID- 2906998 TI - The effect of contact area morphology on operative dental procedures. AB - Measurements of the contact and embrasure areas of adjacent extracted teeth set in plaster blocks were made before groups of dentists undertook preparations on them. The prepared and adjacent teeth were examined and the findings related back to these measurements. Damage to the adjacent teeth was a common finding with both mesial-occlusal-distal (MOD) and complete crown preparations. There was some evidence that easier access to the contact area reduced the frequency of damage to teeth adjacent to MOD preparations. The taper of complete crown preparations did not conform to commonly recommended designs. This investigation highlights the need for greater consideration of approximal tooth surfaces when undertaking preparations and questions the practicality of achieving traditional features of complete crown preparation design. In teaching, greater emphasis should be placed on clinical reality rather than on theoretical, but unachievable ideals. PMID- 2906999 TI - A primer on neurotransmitters and cocaine. PMID- 2907000 TI - Improvement of cocaine-induced neuromodulator deficits by the neuronutrient Tropamine. PMID- 2907001 TI - Are intestinal endocrine cells affected in Hirschsprung's disease? An immunohistochemical study with anti-Leu 7 monoclonal antibody. AB - Specimens from 15 cases of Hirschsprung's disease and 22 control cases of normal guts were studied by the peroxidase-antiperoxidase (PAP) method with with anti Leu 7 (Leu 7) monoclonal antibody (MAb). In the normal human gut, some satellite cells in the enteric plexuses and a few nerve fibers and ganglion cells in the intestinal wall were stained with Leu 7 MAb, while endocrine cells in the intestinal mucosa showed consistent and intense cytoplasmic Leu 7 positivity. In Hirschsprung's disease, the number of Leu 7-positive endocrine cells was significantly low. The mean value of the number of Leu 7-positive endocrine cells per one microscopic field (X300 magnification) was 4.6 +/- 0.6 (+/- SE) in controls and 0.7 +/- 0.3 (+/- SE) in Hirschsprung's disease (P less than .001 by Student's t test). Our findings suggest that the development of endocrine cells in the intestinal mucosa may be closely related to the development of ganglion cells in the enteric plexuses, and that the anti-Leu 7 MAb may be useful for the diagnosis of Hirschsprung's disease when biopsy specimens are limited to the mucosa only. PMID- 2907002 TI - Inhibition of acetylcholinesterase by the H2-receptor antagonist nizatidine. AB - The purpose of the present investigation was to study if the stimulating effect of nizatidine on the intestinal smooth muscle is related to the acetylcholinesterase activity. Isolated segments of guinea pig ileum were used in Tyrode solution at 37 degrees C. Nizatidine (from 3.2 x 10(-6) to 3.2 x 10(-4) M) exerted a concentration-dependent contractile effect on the guinea pig ileum. The average maximum activity (mean +/- S.E.M.) of nizatidine (3.2 x 10(-4) M) was 96.21 +/- 6.19% of the average maximum activity of neostigmine (3.2 x 10(-6) M). The acetylcholine-induced contractions (from 10(-8) to 3.2 x 10(-6) M) were augmented by nizatidine (from 10(-5) to 10(-4) M) in a similar way to that by neostigmine (from 10(-8) to 10(-7) M). The acetylcholine-induced contractions were prevented by acetylcholinesterase (0.1 unit/ml). This acetylcholinesterase activity was inhibited by nizatidine (from 10(-5) to 10(-4) M) and this inhibition was similar to that of neostigmine (from 10(-8) to 10(-7) M). These findings suggest that the stimulating effect of nizatidine on the intestinal smooth muscle of the guinea pig ileum could be explained by the inhibition of acetycholinesterase activity. PMID- 2907003 TI - Non-ionic surfactant effects on hairless mouse skin permeability characteristics. AB - The influence of a range of polyethoxylated non-ionic surfactants upon the transport of methyl nicotinate across hairless mouse skin in-vitro was investigated using standard two-compartment diffusion cells. Those surfactants having a linear alkyl chain greater than C8 and an ethylene oxide chain length of less than E14 caused significant increases in the flux of methyl nicotinate. Surfactants having branched or aromatic moieties in the hydrophobic portion were ineffective. Maximum enhancement of flux was obtained using polyoxyethylene (10) lauryl ether (Brij 36T). Two possible modes of surfactant action are proposed. Initially the surfactant may penetrate into the intercellular regions of the stratum corneum, increase fluidity and eventually solubilise and extract lipid components. Secondly, penetration of the surfactant into the intracellular matrix followed by interaction and binding with the keratin filaments may result in a disruption of order within the corneocyte. The structural specificity required for the latter mechanism may explain, to some extent, the maximum activity obtained with the C12 surfactant. PMID- 2907004 TI - Formation and in-vitro evaluation of theophylline-loaded poly(methyl methacrylate) microspheres. AB - Theophylline-loaded poly(methyl methacrylate) (PMM) microspheres were prepared by the solvent evaporation method. Increasing the drug to polymer ratio increased both the mean particle size of the microspheres and the release rate. Polyethylene glycol (PEG) 4000 was used to improve the release rate of theophylline from the microspheres. No marked effect was observed on particle size distribution of the microspheres as a function of PEG concentration but there was a pronounced effect on drug release. The different particle sizes of microspheres prepared from the same drug to polymer ratio showed no significant difference in drug content, indicating that the ratio between theophylline and PMM remained practically constant regardless of the size of microspheres. Release characteristics of the microspheres were influenced by drug to polymer ratio, the amount of PEG incorporated and the particle size of microspheres. The release rate was slightly higher in simulated gastric fluid than in simulated intestinal fluid. The release profiles of the drug were modified by mixing microspheres of different formulations in different ratios. PMID- 2907005 TI - Effects of methylene blue on the uptake, release and metabolism of noradrenaline in mesenteric arterial vessels. AB - Methylene blue (3, 10 and 30 microM) increased the spontaneous outflow of endogenous dopamine and noradrenaline from sympathetic nerves supplying the dog mesenteric artery and drastically reduced the formation of endogenous dihydroxyphenylglycol (DOPEG). In addition, it decreased the accumulation of [3H]noradrenaline in the tissue, reduced the formation of [3H]DOPEG and [3H]normetanephrine, without altering the formation of [3H]dihydroxymandelic acid. In tissue homogenates of the same blood vessel, methylene blue 30 and 100 microM produced a significant reduction in the deamination of 5-hydroxytryptamine (5-HT), beta-phenylethylamine (beta-PEA) and tyramine. Methylene blue increased the accumulation of [3H]isoprenaline in the tissue, and markedly reduced the formation of [3H]O-methylisoprenaline ([3H]OMI). These results show that methylene blue alters the storage and disposition of the adrenergic transmitter. PMID- 2907006 TI - Study with positron emission tomography of the osmotic opening of the dog blood brain barrier for quinidine and morphine. AB - A canine model was used to evaluate the possibilities offered by positron emission tomography (PET) for the study of drug distribution in the brain during altered states of the blood-brain barrier (BBB). PET was used to monitor the changes in the distribution of [11C]quinidine and [11C]morphine resulting from BBB-disruption by intracarotid infusion of a hyperosmolar mannitol solution. Injection of Evans blue dye allowing post-mortem evaluation of the degree of BBB opening was used as a reference method. Brain radioactivity concentrations observed after i.v. injection of either [11C] quinidine or [11C]morphine were markedly increased by intracarotid mannitol infusion, whereas they were not affected by saline infusion. For both drugs a close correlation was found between the radioactivity concentrations and the degree of Evans blue staining within the brain hemispheres and within smaller regions of interest corresponding to quadrants of a hemisphere. This parallelism between the findings for radioactivity concentrations and Evans blue staining suggests that PET allows the detection of in-vivo changes in brain distribution of drugs resulting from alterations of the BBB permeability. PMID- 2907007 TI - Pharmacological modulation of platelet activating factor (PAF)-induced bronchoconstriction and hypertension in anaesthetized guinea-pigs. AB - The effect of PAF has been examined in anaesthetized guinea-pigs. Intravenous (i.v.) administration of PAF (10 ng kg-1) did not modify the respiratory response but decreased the arterial blood pressure. A high dose of PAF (200 ng kg-1) caused marked bronchoconstriction and concomitant hypertension. The cyclooxygenase inhibitors aspirin (5 mg kg-1) and indomethacin (5 mg kg-1) and the thromboxane A2 (TXA2) receptor antagonist BM-13.177 (1 mg kg-1) failed to inhibit the peak bronchoconstrictive response but significantly inhibited the prolonged response following peak response. These inhibitors also attenuated PAF induced hypertension. On the other hand, the lipoxygenase inhibitors phenidone (10 mg kg-1) and NDGA (5 mg kg-1) and the leukotriene (LT) receptor antagonist FPL-55712 (2 mg kg-1) affected neither bronchoconstriction nor hypertension induced by PAF. However, when aspirin was given in combination with NDGA, phenidone or FPL-55712, the peak and the following prolonged bronchoconstriction were significantly inhibited. The suppression of PAF-induced hypertension by aspirin was not further inhibited by the combination of these inhibitors. These results indicate that in anaesthetized guinea-pigs PAF-induced bronchoconstriction is composed of a dual response, a direct action (peak response) and an indirect action (prolonged response). The latter may be produced by the generation of TXA2 and lipoxygenase products, while PAF-induced hypertension is indirectly mediated by the generation of TXA2. PMID- 2907008 TI - [3H]zacopride: ligand for the identification of 5-HT3 recognition sites. AB - [3H]Zacopride displayed saturable binding to homogenates of the rat entorhinal cortex as measured by the inclusion of the 5-HT3 receptor antagonist BRL43694 in the incubation media. Scatchard analysis indicated a single high affinity binding site (KD 0.76 +/- 0.08 nM, Bmax 77.5 +/- 6.5 fmol (mg protein)-1) with a Hill slope close to unity. Other 5-HT3 receptor antagonists (zacopride, ICS 205-930, GR38032F, GR65630, metoclopramide and cocaine) also competed for the binding site displacing 60% of the total [3H]zacopride binding. 5-HT and 2-methyl-5-HT also were competitive antagonists for [3H]zacopride binding whereas 5-HT1/5-HT2 agonists and antagonists, and agents acting on other neurotransmitter receptors had Ki values greater than 10(-5) M. It is concluded that [3H]zacopride may prove a useful ligand for the study of 5-HT3 recognition sites. PMID- 2907009 TI - Strategy to assess the role of (inter)active metabolites in pharmacodynamic studies in-vivo: a model study with heptabarbital. AB - The purpose of this investigation was to develop a universal experimental strategy by which the role of (inter)active metabolites in in-vivo pharmacodynamic studies can be examined. Heptabarbital was chosen as a model drug and several pharmacokinetic variables which may affect in-vivo concentration pharmacological response relationships were examined. Adult female rats received an i.v. infusion of the drug at one of three different rates (0.225-1.50 mg min 1) until the animals lost their righting reflex (after 11 +/- 1 to 88 +/- 8 min of infusion). The serum concentration of the drug at onset of loss of righting reflex (LRR) increased slightly with increasing infusion rate. The drug concentrations in brain tissue and cerebrospinal fluid (CSF), (mean +/- s.d.: 67 +/- 5 mg kg-1 and 24 +/- 4 mg L-1, respectively, for the lowest infusion rate) were not affected by the infusion rate. The possible contribution of (inter)active metabolites to the pharmacological response of heptabarbital was determined by administration of different i.v. bolus doses (14.1-22.5 mg) resulting in widely differing sleeping-times (7 +/- 3 to 119 +/- 20 min). The concentrations of heptabarbital in serum, brain tissue and CSF at offset of LRR (mean +/- s.d.: 77 +/- 8 mg L-1, 76 +/- 7 mg kg-1 and 29 +/- 5 mg L-1, respectively, for the highest dose) were not affected by the administered dose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2907010 TI - Cardiovascular effects of fibrinopeptide B. AB - The effect of fibrinopeptide B (FpB) on isolated blood vessels and in the intact rat has been investigated. FpB contracted the rabbit superfused aorta preparation (EC50 = 7.5 nmol) and was some 20 times less potent than noradrenaline. Similarly, FpB (0.2-10 nmol) injected into the rat perfused kidney caused dose related, short-lived increases in perfusion pressure and potentiated the vasoconstrictor effect of injected noradrenaline. These effects were associated with increased efflux of PGE2 (but not TxB2) and were reduced but not abolished by indomethacin (10 microM). FpB injected intravenously into the urethane anaesthetized rat exhibited vasoconstrictor activity (EC50 = 2.5 micrograms kg-1) but was less potent than noradrenaline (EC50 = 0.9 micrograms kg-1). The doses of FpB required to contract the rabbit isolated aorta and to constrict the vasculature of the rat kidney occur naturally in the bloodstream of patients with thrombotic disease. FpB released at the site of thrombus formation may play a part in regulating local blood vessel calibre. PMID- 2907012 TI - The effect of the shape of fine particles on the formation of ordered mixtures. AB - A study has been made of the effects of the shape of fine particles on the formation and stability of some ordered mixtures using a specially constructed Y mixer. Irregular particles adhere to indentations on the surface of the carrier particles and form stable ordered mixtures. PMID- 2907011 TI - Effect of levonorgestrel and ethinyloestradiol on vasoconstriction in rat isolated vasculature. AB - Female Sprague-Dawley rats were injected s.c. with 0.2 micrograms day-1 ethinyloestradiol (EE2) or 2.0 micrograms day-1 levonorgestrel (NG), procedures previously shown to increase systolic blood pressure. Increases in perfusion pressure to clonidine, phenylephrine, noradrenaline (NA) and angiotensin II (AII) were observed in rat isolated tail arteries, and to NA in the isolated mesenteric vasculature from steroid and vehicle-treated rats. NG treatment for four weeks produced increases in sensitivity to phenylephrine and NA in rat tail arteries; at 6 weeks the increases in sensitivity had largely disappeared but the maximum responses to clonidine and phenylephrine were increased. No change in sensitivity to AII was observed with NG. In contrast, EE2 treatment for six weeks produced increases in sensitivity to AII, and a decrease in sensitivity and maximum response to clonidine but not to phenylephrine or NA, in tail arteries. Responses to NA in the mesenteric vasculature were increased after 6 weeks NG treatment but unaffected after 12 weeks EE2 treatment. It is concluded that NG treatment stimulates alpha-adrenoceptor number, affinity or receptor-linked Ca2+ events which may contribute to its previously demonstrated hypertensive effect. The increased responsiveness to AII but not the decrease in alpha 2-adrenoceptor responsiveness may be associated with the chronic hypertension induced by EE2. PMID- 2907013 TI - Variations in the friction coefficients of tablet lubricants and relationship to their physicochemical properties. AB - A previously described modified annular shear cell (MASC) has been used to measure the friction coefficients of some powdered tablet lubricants on a steel surface. Commonly used lubricants, as well as others belonging to the stearate group, differed in their friction coefficients at equivalent sample sizes and in the degree of their ability to reduce friction with increasing amounts when evaluated by the apparatus. In all comparisons, magnesium stearate had the lowest friction coefficient. Divalent salts of stearic acid appeared to be better than the other lubricants tested, and among themselves differed only in the extent of their ability to decrease friction. The lubricants also differed in their physical and chemical properties. On evaluation by stepwise regression analysis, such physical properties as projected surface area of lubricant particles, Martin's diameter and bulk density accounted for most of the variation in friction coefficients of the lubricants rather than moisture content or melting point. It could therefore be suggested that particle size and/or surface area parameters be incorporated in product specifications to ensure reproducible functionality. PMID- 2907014 TI - Cephaloridine resistance in gram-negative bacteria isolated in Scotland. AB - The incidence of cephaloridine resistance (minimum inhibitory concentration, MIC greater than 8 mg L-1) in isolates from urinary tract infections was 45.1% in Glasgow, 22.6% in Dundee and 25.9% in Edinburgh. The incidence of ampicillin resistance (MIC greater than 8 mg L-1) was even higher:- being 45.2% in Dundee and 48.5% in Edinburgh. In Glasgow, the incidence was 71.9% which is the highest proportion of ampicillin resistance reported in the United Kingdom. The cephaloridine resistant strains were examined for beta-lactamase production. Amongst these strains 50.8% produced only a chromosomal beta-lactamase, whereas 47.9% produced beta-lactamases which were potentially plasmid-mediated on the basis of biochemical tests. Only 1% of the resistant strains produced no detectable beta-lactamase. PMID- 2907015 TI - Pharmacological profile of a chromanamine analogue (DP-6OH-3CA) of the selective presynaptic dopamine agonist N,N-dipropyl-7-hydroxy-2-aminotetralin. AB - The pharmacological profile of an oxygen isostere of the selective presynaptic dopamine agonist DP-7OH-AT, i.e. dipropyl-6-hydroxy-3-chromanamine (DP-6OH-3CA) has been evaluated in various receptor binding, neurobiochemical and behavioural experiments. The chromanamine displaced the 3H-labelled dopamine ligands, 5,6 DPAT and N-0437, with Ki values of 106 and 143 nM, respectively. In in-vivo biochemical models for presynaptic activity the chromanamine induced a half maximal effect in the gamma-butyrolactone reversal test at 6.8 mumol kg-1 and had an ED70 value of 40 mumol kg-1 for HVA decrease in the striatum. In behavioural models for postsynaptic dopaminergic activity a half-maximal effect for the induction of stereotypy was reached at 100 mumol kg-1 and reversal of the effects of reserpine to a level of 200 counts was induced at 11 mumol kg-1. On comparison of these results with the results obtained with the carbon analogue of DP-6OH 3CA, i.e. DP-7OH-AT, it is apparent that the chromanamine has a reduced potency for dopamine D2 receptors in in-vitro and in-vivo models. The selectivity for presynaptic dopamine receptors was lower than with DP-7OH-AT and the isomeric chromanamine, DP-8OH-3CA, indicating that the optimal position of the hydroxyl group for presynaptic selectivity is in the 8 and not in the 6 position for the chromanamines. PMID- 2907016 TI - Dopamine receptor modulation of corticosterone secretion in neonatal and adult rats. AB - The effects of the dopamine agonist, pergolide, upon plasma corticosterone levels have been studied in 30 day old neonatal and adult rats. Dose-related elevations in corticosterone were observed at both ages and these elevations were blocked by the dopamine (D2) receptor antagonist spiperone. These studies demonstrate that dopaminergic neurochemical control of the hypothalamus-pituitary-adrenal axis exists in four week old rats in contrast to our previous studies which have shown opioid control to be absent at this age. It appears that neurochemical control of corticosterone is dissimilar in the neonate. PMID- 2907017 TI - Enhancement of adenosine-induced relaxant responses of the guinea-pig isolated taenia coli and aortae by a novel nootropic agent BY-1949: comparison with dipyridamole. AB - In muscle strips of guinea-pig taenia coli and aortae, the effects of 3-methoxy 11-methyldibenz[b,f][1,4]oxazepine-8-carboxylate (BY-1949) on the relaxant response to adenosine have been compared with those of dipyridamole. BY-1949 (3 x 10(-5)-10(-4) M) as well as dipyridamole (3 x 10(-7)-10(-5) M) resulted in a significant potentiation of relaxant responses to a cumulative administration of adenosine (10(-6)-10(-3) M), but the drugs did not affect the response to noradrenaline and acetylcholine. The results indicate that BY-1949 exerts a selective potentiating effect on reactivity to exogenous adenosine. PMID- 2907018 TI - Brain penetration of orally administered sodium pyroglutamate. AB - The absorption and brain penetration of [3H]pyroglutamate was determined after oral administration to rats. Gas-liquid chromatography of the methylated derivatives followed by mass fragmentometry was used to analyse the plasma and brain levels of pyroglutamate. [3H]Pyroglutamate was separated from other labelled compounds by thin layer chromatography. The administration of 500 mg kg 1 [3H]pyroglutamate resulted in a 30-fold increase in plasma levels and a doubling in the brain levels. Over 60% of the cerebral radioactivity was present as [3H]pyroglutamate demonstrating that pyroglutamate is not only well absorbed but also penetrates in significant amounts into the brain. PMID- 2907019 TI - Identification of 5-HT3 recognition sites in the ferret area postrema. AB - The 5-HT3 receptor antagonist [3H]zacopride was used to identify 5-HT3 recognition sites in the ferret area postrema. Specific binding was determined by the inclusion of the 5-HT3 receptor antagonist BRL 43694 in the incubation media, and was shown to be much higher in the area postrema than in other brain regions. The increased binding in the area postrema may reflect either a greater number of binding sites, a higher affinity for such sites, or both. The results indicate that 5-HT3 recognition sites are present within the area postrema and may afford an antiemetic site of action for zacopride and other 5-HT3 receptor antagonists. PMID- 2907020 TI - Effects of BN 52063 and other agents inhibiting platelet-activating factor induced contractile responses in rat portal vein. AB - Platelet-activating factor (PAF-acether) is a potent agonist (EC50: 3.2 x 10(-8) M) of isolated rat portal vein. BN 52063 (composed of BN 52020, BN 52021 and BN 52022; molar ratio 2:2:1) specifically inhibits PAF-acether (10(-7) M) induced tone (IC50: 3.9 x 10(-5) M). Salbutamol (IC50: 3.1 x 10(-7) M), forskolin (IC50: 3.1 x 10(-6) M) and theophylline (IC50: 2.25 x 10(-4) M) are also effective in inhibiting PAF-acether-induced contractile responses and all excepting forskolin, show a certain specificity in this action. The basal myogenic activity of the rat portal vein is dose-dependently decreased by salbutamol (IC50: 1.2 x 10(-7) M), forskolin (IC50: 2.6 x 10(-6) M) and theophylline (IC50: 2.3 x 10(-4) M) whereas BN 52063 has no effect. The data suggest that rat portal veins possess specific PAF-acether receptors sensitive to BN 52063 and that PAF-acether effects could be inhibited by compounds which can bypass these putative receptors and modulate cAMP levels. PMID- 2907021 TI - Circadian phase-dependent pharmacokinetics and acute toxicity of mepivacaine. AB - The aim of this study was to investigate the possible influence of the time of administration on mepivacaine acute toxicity and kinetics in mice. Four different groups of adult male NMRI mice maintained under controlled environmental conditions (lights on: = 0600-1800 h) were injected at one of the following times: 1000, 1600, 1900, 2200, 0100 and 0400 h with one of four doses of mepivacaine at each time point to establish the acute toxicity (LD50). To assess chronokinetics, a single 60 mg kg-1 i.p. dose of mepivacaine was given to adult male NMRI mice at four fixed times: 1000, 1600, 2200 and 0400 h. Mepivacaine plasma concentrations were determined by GLC. Our data showed significant 24 h variations in the following parameters: Highest tmax value = 0.366 +/- 0.073 h at 1000 h (P less than 0.005, amplitude, maximum-minimum/mean x 100, = 184%), highest Cmax/tmax ratio = 177.17 +/- 9.49 at 2200 h (P less than 0.005, amplitude = 192%), highest Vd = 0.842 +/- 0.23 L kg-1 at 2200 h (P less than 0.005, amplitude = 158%) and highest beta phase elimination half-life = 5.408 +/- 1.36 h at 2200 h (P less than 0.025, amplitude = 145%). Cmax (amplitude = 15%), AUC infinity 0 (amplitude = 24%) and clearance (amplitude = 23%) were not significantly time-dependent. These data demonstrate a temporal pattern of mepivacaine kinetics similar to those reported previously for bupivacaine. The temporal changes in mepivacaine-induced acute toxicity may result in part from its chronokinetic changes. PMID- 2907022 TI - Oesophageal transit of small tablets. AB - Oesophageal transit has been studied in six asymptomatic subjects aged 29-80 years. Using gamma scintigraphy, the transit of a liquid and five small tablets was monitored in each subject. All the subjects exhibited normal liquid swallowing, with 50% oesophageal clearance times of less than 5 s. In three subjects all the tablets passed through the oesophagus within 6 s, but transit was prolonged in 60% of the swallows in the other subjects. Tablet hold up occurred more frequently in the elderly. An additional drink of water cleared all lodged tablets into the stomach. To minimize possible mucosal irritation, the taking of even small tablets should be followed by an additional drink of water. PMID- 2907023 TI - Determination of the critical stress intensity factor (KIC) of compacted pharmaceutical powders by the double torsion method. AB - The critical stress intensity factor KIC has been determined for compacts prepared at different pressures from both Avicel PH101 and sorbitol "Instant', by means of a double torsion method. This method avoids the need for displacement measurement and the introduction of notch into the specimens, both of which present problems with pharmaceutical materials. Measurements of fracture loads for such specimens were reproducible. The values of KIC derived for both materials were found to increase linearly with increase in compaction pressure and linearly with decrease in specimen porosity. Extrapolation of the latter relationship to zero porosity gave values of 1.81 and 0.69 MN m-3/2 for the KIC of Avicel PH101 and sorbitol "Instant', respectively. PMID- 2907024 TI - The sorption of isosorbide dinitrate to intravenous delivery systems. AB - The sorption of isosorbide dinitrate from 0.9% sodium chloride and 10% glucose solutions, by intravenous delivery systems has been investigated under simulated infusion conditions. Isosorbide dinitrate was stable in both 0.9% sodium chloride and 10% glucose solutions. Intravenous fluid containers, burettes, a syringe, infusion sets and end-line filters were evaluated. Glass containers, methacrylate butadiene styrene burettes and polybutadiene giving sets did not sorb isosorbide dinitrate. Neither did polypropylene syringes when a 10% glucose solution was used. The sorption of isosorbide dinitrate to end-line filters was unimportant but there was a significant loss to the PVC tubing used to connect the filter housing to the catheter. PMID- 2907025 TI - Structure-activity studies of fentanyl. AB - The preparation of analogues of fentanyl with para substituents in the anilino aromatic ring, anilino nitrogen separated from phenyl by methylene or bimethylene, and phenacyl replacing propionyl as the N-acyl substituent is reported. Although all para substituents examined depressed antinociceptive potency in rats, most analogues of this kind were more effective than morphine and the p-F, I, and Me derivatives were only a few-fold less active than fentanyl. Separation of anilino nitrogen from phenyl lowered potency with N phenethyl analogues retaining reasonable levels of activity (greater than morphine). All the phenacyl analogues were of low potency or inactive. Diagnostic details of the mass spectra of analogues likely to be encountered as "designer drugs' are appended. PMID- 2907026 TI - Influence of lipophilicity and chirality on the selectivity of ligands for beta 1 and beta 2-adrenoceptors. AB - Eudismic and QSAR analyses are reported for the beta 1- and beta 2-adrenoceptor affinities and beta 1-selectivity of 10 enantiomeric pairs of ligands with only N isopropyl or N-t-butyl groups. For both receptors, the eudismic index (ratio of affinity) increases with the affinity of the eutomers. However, the affinity of the distomers for the beta 2-adrenoceptor is relatively high, suggesting additional hydrophobic interactions. This is confirmed by various correlations between affinities and lipophilicities, showing that the affinity for beta 2 adrenoceptors is slightly more dependent on lipophilicity than that for beta 1 adrenoceptors. As a result, the beta 1-selectivity of the investigated beta 1 adrenoceptor ligands is strongly and negatively correlated with their lipophilicity (r = -0.942). PMID- 2907027 TI - Definition of the in-vivo accumulation of [3H]spiperone in brain using haloperidol and sulpiride to determine functional dopamine receptor occupation. AB - The in-vivo administration of [3H]spiperone caused an accumulation of radioactivity in the substantia nigra, tuberculum olfactorium, nucleus accumbens, striatum and frontal cortex when compared with cerebellar levels. Haloperidol (0.01-1.0 mg kg-1 i.p.) dose-dependently prevented the accumulation of [3H]spiperone in the substantia nigra, tuberculum olfactorium, striatum and nucleus accumbens. Sulpiride (10-160 mg kg-1 i.p.) dose-dependently prevented the accumulation of [3H]spiperone only in the substantia nigra. The effects of sulpiride on other areas were not consistent; there was a suggestion of a reduction in the accumulation of [3H]spiperone in tuberculum olfactorium and striatum, but not in nucleus accumbens. Neither haloperidol (0.01-1.0 mg kg-1 i.p.) nor sulpiride (10-160 mg kg-1 i.p.) caused displacement of [3H]spiperone from the frontal cortex. Both haloperidol (0.01-0.5 mg kg-1) and sulpiride (10-80 mg kg-1) increased striatal and mesolimbic HVA concentrations. Haloperidol potently blocked apomorphine-induced stereotypy but sulpiride was only effective at the highest dose employed. The functional effect produced by haloperidol correlated with its ability to define [3H]spiperone binding in-vivo to dopamine receptors in the substantia nigra, striatum and tuberculum olfactorium. In contrast, there was no correlation between functional effect of sulpiride and its ability to define [3H]spiperone binding in-vivo. PMID- 2907028 TI - The effects of 1-methyl-4-phenylpyridinium ion (MPP+) on the efflux and metabolism of endogenous dopamine in rat striatal slices. AB - 1-Methyl-4-phenylpyridinium ion (MPP+) was shown to accumulate concentration dependently in slices from rat striatum. At 10 microM, MPP+, the tissue concentration was found to be 118 +/- 9 microM following 75 min of incubation. The accumulation of MPP+ was reduced in the presence of 10 microM of the selective dopamine uptake inhibitor GBR 12909 (-50%) or by destruction of the dopaminergic terminals by complete hemisection of the forebrain 4 days before the experiments (-75%). Accumulation of MPP+ in the catecholamine-poor occipital cortex and cerebellum was only 25% of that obtained in striatum. Reserpine pretreatment of the rats in-vivo did not modify the accumulation of MPP+ in the striatal slices. MPP+ (1-10 microM) increased the net efflux of dopamine and reduced the efflux of the dopamine metabolite DOPAC from the striatal slices. The effect on dopamine was readily diminished if MPP+, after a 15 min incubation, was then omitted from the medium. In contrast, the DOPAC efflux was reduced for 75 min even though MPP+ was present in the incubation medium only for the first 15 min. In the presence of the monoamine oxidase inhibitor, pargyline (350 microM), MPP+ also produced an increase in dopamine efflux. In normal medium, the presence of the dopamine uptake inhibitor GBR 12909 (10 microM), or the absence of calcium, failed to modify the MPP+-induced increase in dopamine efflux. MPP+ also increased dopamine efflux from slices from reserpinized rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2907030 TI - Dihydroergotoxine-induced bradycardia in rats. AB - Dihydroergotoxine (0.01-0.3 mg kg-1 i.v.) decreased heart rate in pentobarbitone anaesthetized rats. The bradycardia was reduced but not blocked by pre-treatment with guanethidine, yohimbine, propranolol or pithing. It was not prevented by bivagotomy, atropine, sulpiride or haloperidol. Dihydroergotoxine failed to affect, either the bradycardia produced by electrical stimulation of the vagus, or the cardioacceleration induced by i.v. isoprenaline. The increase in heart rate elicited in pithed rats by electrical stimulation of the spinal cord was reduced by dihydroergotoxine; this effect being inhibited by yohimbine but not by sulpiride. In conclusion, the main mechanism by which dihydroergotoxine (i.v.) induces bradycardia in the rat involves stimulation of alpha 2-adrenoceptors located predominantly at the cardiac sympathetic nerve endings. PMID- 2907029 TI - Properties of a semicarbazide-sensitive amine oxidase in human umbilical artery. AB - The metabolism of some aromatic amines by amine oxidase activities in human umbilical artery homogenates has been studied. The inhibitory effects of clorgyline showed that 5-hydroxytryptamine (5-HT) and tryptamine, 1 mM, were predominantly substrates for monoamine oxidase (MAO) type A, whereas MAO-A and B were both involved in the metabolism of beta-phenylethylamine (PEA), 100 microM, and tyramine, 1 mM. About 20-30% of tyramine and PEA metabolism was resistant to 1 mM clorgyline, but sensitive to inhibition by semicarbazide, 1 mM, indicating the presence of a semicarbazide-sensitive amine oxidase (SSAO). Benzylamine, 1 mM, appeared to be metabolized exclusively by SSAO with a Km (161 microM) at pH 7.8 similar to that found for SSAO in other human tissues. Tyramine and PEA were relatively poor substrates for SSAO, with very high apparent Km values of 17.6 and 13.3 mM, respectively, when determined in the presence of clorgyline, 10(-3) M, added to inhibit any metabolism of those amines by MAO activities. However, kinetic studies with benzylamine indicated that clorgyline, 10(-3) M, also appears to inhibit SSAO competitively such that the true Km values for tyramine and PEA may be about 60% of those apparent values given above. No evidence for the metabolism of 5-HT or tryptamine by SSAO was obtained. The aliphatic amine methylamine was recently shown to be a specific substrate for SSAO in umbilical artery homogenates. We have used benzylamine and methylamine as SSAO substrates in histochemical studies to localize SSAO in tissue sections.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2907031 TI - Importance of D-2 mechanisms in the reversal of reserpine hypothermia in the mouse. AB - The D-2 agonist LY 171555 (0.05, 0.1, 0.2 mg kg-1 s.c.) but not the D-1 agonist SK&F 38393 (5, 10, 20 mg kg-1 s.c.) reduced reserpine-induced hypothermia (RIH) in mice. This effect was antagonized by the D-2 antagonist (-)-sulpiride (50 mg kg-1 i.p.) but not by the D-1 antagonist SCH 23390 (0.1 mg kg-1 s.c.). SK&F 38393 (20 and 1 mg kg-1 s.c.) did not alter the effect of LY 171555 (0.1 and 0.2 mg kg 1) on RIH, but administration of both LY 171555 (0.2 mg kg-1 s.c.) and SK&F 38393 (1 mg kg-1 s.c.) antagonized the reserpine-induced sedation. PMID- 2907032 TI - Sustained release of indomethacin from chitosan granules in beagle dogs. AB - The potential of chitosan granules as an oral sustained-release dosage form of indomethacin has been compared with conventional capsules in beagle dogs. When a commercial capsule was administered orally, the plasma concentrations reached the maximum level in 30 min. The granules did not give a sharp peak to the plasma concentration, but produced a sustained plateau of the drug. This may be due to the slow rate of release and a longer residence time in the stomach. Thus, in terms of reducing the peak in plasma concentration and maintenance of drug concentration in plasma, the chitosan granules were superior to conventional capsules. PMID- 2907033 TI - The stability of morphine in isobaric and hyperbaric solutions in a drug delivery system. AB - Intrathecal preparations of morphine for use in intractable pain must contain no preservatives. They are generally formulated in saline (isobaric) or dextrose (hyperbaric) which raises questions of stability. The behaviour of morphine in hyperbaric and isobaric solutions stored in a reservoir for implantation has been examined and the effect of temperature and the time of contact of morphine with the different components of the reservoir as well as the sterilization procedure have been investigated. The best stability was observed with a hyperbaric solution in which there was 15 to 20 times less pseudomorphine than in the isobaric solution, which was found to contain 1% pseudomorphine after 1 month of storage at 37 degrees C in the reservoir. Similar solutions stored in ampoules did not degrade. PMID- 2907034 TI - Intestinal absorption of cephalosporin antibiotics: correlation between intestinal absorption and brush-border membrane transport. AB - The absorption of seven cephalosporin antibiotics from the in-situ intestinal loop at pH 7.4 and their transport by brush-border membrane vesicles in the presence of an inward H+ gradient ([pH]i = 7.5, [pH]o = 6.0) were examined. A good correlation was found between the intestinal absorption rate and the initial uptake rate by brush-border membrane vesicles. The data suggest that the transport study using intestinal brush-border membrane vesicles is useful as a model system for the intestinal absorption of beta-lactam antibiotics. PMID- 2907035 TI - Effects of proenkephalin products on rat cardiac and vascular tissue in-vitro. AB - The cardiovascular effects of the four proenkephalin products [Met]-enkephalin (ME), [Leu]-enkephalin (LE), [Met]-enkephalyl-arg6phe7 (MEAP) and [Met] enkephalyl-arg6-gly7-leu8 (MEAGL) have been studied on the isolated spontaneously beating rat atria and the perfused rat mesentery in-vitro. All four peptides (at concentrations up to 10(-6)M and in the presence of peptidase inhibitors) had no direct effect on atrial rate or contractility and did not alter responses to noradrenaline or field stimulation. In addition, the peptides had no effect on the perfusion pressure of the mesentery and did not alter vasoconstrictor responses to noradrenaline. The results show that proenkephalin products are without direct or modulating effects on atrial muscle or mesenteric vasculature of the rat, and suggest that there is no endogenous opioid control in these tissues. PMID- 2907036 TI - Effect of tiopronin on prostaglandin synthesis in rabbit kidney medulla slices. AB - The effect of 2-mercaptopropionylglycine (tiopronin), which is widely used for the treatment of various hepatic disorders, on the generation of medullary prostaglandins (PG) E2 and F2 alpha has been examined. Tiopronin had a potent inhibitory effect on PG E2 formation. Simultaneously, PG F2 alpha production was increased. In the presence of tiopronin the net increased amount of PG F2 alpha was much smaller than the net decreased amount of PG E2 (6-20%). These results suggest that tiopronin has the potential to modulate PG E2 and F2 alpha synthesis by affecting endoperoxide E2 isomerase or endoperoxide reductase and that this effect may represent some pharmacological action of the drug. PMID- 2907037 TI - Excretion and distribution of [14C]rhein and [14C]rhein anthrone in rat. AB - After single intracaecal administration of [14C]rhein (25 mg kg-1) and [14C]rhein anthrone (20 mg kg-1) to rats, the summated recovery rates of 14C after five days were in urine 37(+/- 8.3)% and 2.8(+/- 0.4)% and in faeces 53(+/- 9.5)% and 95 (+/- 10.1)%, respectively. The clearance of radioactivity from the organs and tissues was almost complete within three days, with the exception of the kidney which exhibited pronounced retention of radioactivity even after five days (less than 61% of 24 h values). Extracts of faeces from animals treated with [14C]rhein of [14C]rhein anthrone, revealed rhein as well as other radioactive substances, which chemically did not react as 1,8-dihydroxyanthraquinones. PMID- 2907038 TI - Antihistaminic and anticholinergic activities of mequitazine in comparison with clemizole. AB - The antihistamine and anticholinergic properties of mequitazine have been investigated and compared with those of clemizole. Both mequitazine and clemizole antagonized the effect of histamine in guinea-pig ileum competitively, the pA2 values calculated by Schild plot were 9.95 +/- 0.44 for mequitazine and 10.54 +/- 0.44 for clemizole. Mequitazine at 10(-7) M produced a parallel shift of the dose response curve to acetylcholine in the rat duodenum, clemizole and the lower doses of mequitazine failed to modify the effect of acetylcholine. The potency of mequitazine and clemizole as H1-histamine blockers is similar, but only mequitazine at highest concentration used showed anticholinergic activity. PMID- 2907039 TI - A comparison of the effects of oxodipine and nifedipine on rat vas deferens. AB - The effects of oxodipine, a new dihydropyridine, were studied and compared with those of nifedipine in the complete vasa deferentia and in the prostatic and epididymal halves of the rat vas deferens. Oxodipine and nifedipine, 10(-9) -10( 6)M, produced a dose-dependent inhibition of the contractile responses induced by single pulse stimulation, noradrenaline (3 x 10(-5)M) and high-K (50 mM). The inhibitory effects of oxodipine were significantly reduced in high Ca media. From these experiments it is concluded that oxodipine, like nifedipine, produced a similar and potent inhibitory effect of the contractile responses induced in the rat vas deferens. PMID- 2907040 TI - The influence of concentration of two salicylate derivatives on rectal insulin absorption enhancement. AB - 3,5-Diiodosalicylate sodium (DIS), a highly lipophilic salicylate, was evaluated against 5-methoxysalicylate sodium (MS) as a potential adjuvant absorption promoter for rectal insulin delivery. Comparative blood glucose measurements were made using the two adjuvants under identical conditions as promoters of rectal insulin absorption in rats. Concentrations of DIS greater than and including 0.1 M produced an unexpected, progressive decrease in adjuvant activity as determined by a decline in observed hypoglycaemic response. This was not due to formation of an insulin-DIS complex. The adjuvant MS produced a classical, sigmoidal log-dose response curve. Possible reasons for the occurrence of the DIS optimum phenomenon are discussed as well as are the observed differences in adjuvant potency of these agents in a propylene glycol-containing vehicle. PMID- 2907042 TI - New method for testing the absorbency of surgical dressings. AB - Absorbent cellulose dressings have been tested by immersion in a standard aqueous solution of picric acid followed by standard draining, elution of the picric acid, and measurement of the absorbance of the yellow colour at 355 nm. Six samples of gauze were graded by this procedure, and two considered unsatisfactory, despite all sinking in less than 10s. Filmated gauzes and unwoven dressings required greater dilution for the absorbance readings, reflecting their different structures. PMID- 2907041 TI - An assay procedure to compare sorptive capacities of activated carbon dressings: the detection of impregnation with silver. AB - A semiquantitative assay procedure for the estimation of uptake of diethylamine by activated carbon dressings has been developed. The procedure involves the use of Nessler's reagent as a comparative indicator. The use of diethylamine allows the concomitant detection of silver with which the dressings may be impregnated. The implications of silver/amine complex formation during dressing use are discussed. Quantification of the silver content of one such fabric was carried out by atomic absorption spectrophotometry. A silver content of 2770 ppm was found. It is suggested that this method might be suitable for adoption as the basis for a pharmacopoeial assay procedure for activated carbon dressings. PMID- 2907043 TI - Plasma levels of opioid material in man following sublingual and intravenous administration of buprenorphine: exogenous/endogenous opioid interaction? PMID- 2907044 TI - Indomethacin and cartilage breakdown. PMID- 2907045 TI - Identification of 5-HT3 recognition sites in human brain tissue using [3H]zacopride. PMID- 2907046 TI - Regulation of metabolic branch points of aromatic amino acid biosynthesis in Pichia guilliermondii. AB - The regulatory properties of the enzymes involved in the aromatic amino acid biosynthesis of Pichia guilliermondii were investigated and compared with the regulatory pattern found in other yeast species. 3-Deoxy-D-arabino-heptulosonate 7-phosphate (DAHP) synthase, anthranilate synthase, chorismate mutase and prephenate dehydrogenase are key regulatory enzymes in P. guilliermondii. Two distinctly regulated isozymes of DAHP synthase, the initial pathway enzyme, which is inhibited by tyrosine or phenylalanine were separated by DEAE-cellulose chromatography and were characterized. Tryptophan is an excellent feedback inhibitor of anthranilate synthase, the first definite step in tryptophan biosynthesis. There are two controlled enzymes within the specific synthesis of phenylalanine and tyrosine, chorismate mutase and prephenate dehydrogenase. Chorismate mutase exhibits a balanced allosteric responsivity to phenylalanine and tyrosine, when these are used as inhibitor; tryptophan acts as an allosteric activator. Tyrosine is an effective inhibitor of prephenate dehydrogenase, whereas the activity of prephenate dehydratase is not affected by any of the aromatic amino acids. The synthesis of the enzymes in the yeast was not repressed by any single exogenous aromatic amino acids, nor by combinations of the same. PMID- 2907047 TI - Antipsychotic properties of new N-(4-substituted-1-piperazinylethyl)- and N-(4 substituted-1-piperidinylethyl)-phthalimides. AB - A series of N-(4-phenyl- and 4-pyridyl-1-piperazinylethyl)- and N-(4-phenyl-1 piperidinylethyl)-phthalmides were synthesized and tested for antipsychotic activity. All compounds suppressed the spontaneous motor activity and the apomorphine-induced climbing in mice and pergolide-induced locomotor activity in rats, demonstrating psychotropic properties equal to the corresponding properties of sulpiride. Although the compounds, like sulpiride, were less potent than haloperidol in blocking the locomotor activities, they caused no catalepsy, a major side effect following treatment with conventional antipsychotic agents. It is likely that the new compounds produce their neuroleptic activities through inhibition of limbic dopamine receptors. PMID- 2907048 TI - Changes in binomial parameters of quantal release at crustacean motor axon terminals during presynaptic inhibition. AB - 1. The effects of presynaptic inhibition on quantal release of transmitter were investigated at neuromuscular junctions of the motor axon supplying one of the limb muscles of a crab (Pachygrapsus crassipes). 2. Binomial analysis of transmitter release recorded at selected neuromuscular junctions with an extracellular 'macro-patch' electrode indicated high probability of release (p) from a limited number of available sites (n). During presynaptic inhibition, both n and p were reduced. 3. The binomial model provided a good description of results from non-inhibited junctions. During presynaptic inhibition, results from some junctions could be described by the binomial model, while those from other junctions could not. An interpretation of this finding is that presynaptic inhibition differentially affects the probability of release at various release sites of the neuromuscular junctional complex. 4. A morphological study of the region of transmitter release under the macropatch electrode was made. Release dependent uptake of horseradish peroxidase (HRP) into presynaptic terminals was restricted to the region under the recording electrode, by perfusing the preparation with calcium-free solution containing HRP. Transmitter release, and HRP uptake, occurred only at the site of the electrode, which was filled with a calcium-containing solution. Subsequently, serial sections were prepared for electron microscopy and the region of transmitter release was reconstructed. 5. Numerous axo-axonal synapses were found in the HRP-labelled region. Thus, the morphological prerequisite for presynaptic inhibition exists at the site of transmitter release, and not exclusively at a more remote region. 6. The number of morphologically identified excitatory neuromuscular synapses exceeded the 'release sites' estimated from the binomial model (n) by a wide margin. Morphological differences among synapses were observed. It is proposed that not all morphologically identified synapses participated in transmitter release under the experimental conditions employed. Thus, morphologically defined synapses are likely to be non-uniform in their response properties, including probability of transmitter release (p). PMID- 2907050 TI - [Immunotoxicity of benzodiazepines. Influence on contact hypersensitivity to picryl chloride in mice]. PMID- 2907049 TI - Burst-patterned stimulation promotes nicotinic transmission in isolated perfused rat sympathetic ganglia. AB - 1. Intracellular recordings of small nicotinic excitatory postsynaptic potentials (EPSPs) were made from rostral cells in superior cervical ganglia (SCG) of rats during and after test stimulation of small preganglionic fibre bundles, while perfusing the isolated ganglia via their arterial vasculature. Perfusion, in contrast to superfusion of desheathed ganglia, (a) produced much more rapid and complete equilibration of drugs and ions at synaptic sites, (b) greatly reduced depression of EPSPs during high-frequency stimulation, and (c) largely prevented slowing of conduction, presumably by minimizing accumulation of K+ in the intercellular spaces surrounding these sites. 2. Preganglionic inputs were found to fall into two major groups: those in which the EPSP amplitude during 200 pulse trains was facilitated and others in which it was depressed as stimulation frequency in the train was increased from 2 to 20 Hz or from 0.2 to 1.25 Hz. Both the facilitation and the depression were presynaptic, since they occurred without changes in miniature EPSP amplitude. 3. The maximum maintained facilitation was reached at 5-10 Hz with a value 1.26 times the 1.0 Hz control. This was associated with an increase in the binomial parameter n. While long 20 Hz trains produced a similar facilitation to an early plateau, and an increase in n, EPSP amplitude declined as the train progressed. This was associated with a decrease in the binomial parameter p. 4. Unlike the 20 Hz trains, stimulation with 0.5 s long, 20 Hz bursts given every 8 s produced a marked potentiation in facilitating units and this was maintained for as long as the stimulation was continued (3-11 min). Burst-patterned potentiation was 1.66 times larger than the facilitation evoked by tonic stimulation at the same average frequency (1.25 Hz), and more than twice that achieved with long, 200 pulse trains. The potentiation was associated with increases in both n and p in the first EPSP of the burst and mainly with an increase in n at the end of the burst. Potentiation persisted unchanged for about 30 s following the return to control 0.2 Hz stimulation, before declining to control levels over the next 2-3 min. Depressing units on average showed neither burst-patterned potentiation nor post-burst-patterned potentiation. 5. All inputs tested in Locke solution in which Ca2+ was reduced to 0.5 mM with addition of 1.2 mM-Mn2+ or 3.8 mM-MgCl2 exhibited a pronounced facilitation within each burst but no extension of potentiation into ensuing bursts. Both burst-patterned potentiation and the post-burst-patterned potentiation were abolished.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2907051 TI - L-glutamate-induced membrane hyperpolarization and behavioural responses in Paramecium tetraurelia. AB - Paramecium tetraurelia is attracted to L-glutamic acid concentrations of 10(-9) M to 10(-4) M in a behavioural assay. Electrophysiological studies show that P. tetaurelia responds to L-glutamate application with hyperpolarization. This response is transient, even in the continued presence of the stimulus. The concentration dependence of the membrane potential response is similar to that of the behavioural responses, although the threshold concentration of L-glutamate required for hyperpolarization is three orders of magnitude lower than for attraction. The membrane potential response to L-glutamate persists following artificial deciliation of P. tetraurelia. While application of L-glutamate to P. tetraurelia invariably elicits a hyperpolarization, withdrawal of the stimulus frequently results in a second transient membrane response, in the form of either a hyperpolarization or a depolarization. It is suggested that these 'off responses' may have a significant role in maintaining a behavioural response to L glutamate. PMID- 2907052 TI - The angry adolescent. Treatment versus containment practices. PMID- 2907053 TI - Beta adrenoceptor blockade is associated with increased survival in male but not female hypertensive patients: a report from the DHSS Hypertension Care Computing Project (DHCCP). AB - The DHCCP is a multicentre observational study of patients being treated for hypertension in the United Kingdom. The influence of the type of anti hypertensive therapy on survival was examined in 2,697 patients followed from 1971 with 206 deaths up to November 1981. Patients were classified by three types of treatment after one year in the project: betablockers (1,387), methyldopa (452) and others (667), (70% on diuretics only). The data were analysed both for all patients and for a subset excluding patients with previous ischaemic heart disease by all cause and IHD age-adjusted rates and life table analysis. Men on beta blockers had lower rates for total mortality, when compared with men on methyldopa (64% of the methyldopa rate, P less than 0.05) and when compared with men on other treatments (76% of the other treatment rate, P less than 0.1). The results for IHD mortality were similar. This improved survival of men in the beta blocker group was also found in the subset with no prior history of IHD. The benefit of beta blockers was not apparent in women: the lowest rates were observed for women on methyldopa, but the confidence limits for the ratios of relative rates were wide. Adjustment for blood pressure and cigarette smoking using the Cox proportional hazards model did not substantially modify the ratios of the mortality rates for the treatment groups. A sub-group analysis showed the reduction in all cause and IHD mortality associated with beta blockers was mainly due to the effect in non-smoking men.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2907054 TI - Carrier detection through the use of abnormal deletion junction fragments in a case of haemophilia B involving complete deletion of the factor IX gene. PMID- 2907055 TI - Effects of glutamic acid on cardiac function and energy metabolism of rat heart during ischaemia and reperfusion. AB - The effects of exogenous glutamate (20 mM) on myocardial energy metabolism and cardiac function during low-flow ischaemia and subsequent reperfusion were studied in isolated working rat hearts. Hearts were made severely ischaemic for 60 min by reducing the perfusion rate to 0.17 ml/min, and then reperfused for 30 min. Low-flow ischaemia resulted in a 50% reduction of myocardial ATP, a 70% reduction of both creatine phosphate (CP) and GTP, and a 250% rise in AMP. After reperfusion, CP was restored to normal levels but ATP and GTP remained significantly low. All hearts failed completely to recover cardiac pump function. The addition of glutamate to the perfusate during low-flow ischaemia had no significant effect on myocardial high-energy phosphates (HEP) but slightly increased succinate production. Subsequent reperfusion without added glutamate resulted in the recovery of 62% of pre-ischaemic aortic flow rate, as well as restoration of myocardial ATP and GTP to 70% of their control values and of creatine phosphate to supranormal levels. Reperfusion with added glutamate did not raise HEP levels any further but did increase recovery of cardiac function to 92% or more of pre-ischaemic values. Thus, by mechanism(s) which are not yet clear but which may include an increase in HEP via anaerobic succinate production, elevated levels of exogenous glutamate exert a highly beneficial effect on the post-ischaemic recovery of cardiac function. PMID- 2907056 TI - [Biochemical markers in alcoholic drinking--special reference to serum enzymes]. PMID- 2907057 TI - [Alcohol drinking and blood pressure]. PMID- 2907058 TI - [Is renal renin release mediated through beta 1- or beta 2-adrenoceptors?]. PMID- 2907059 TI - [A case of chronic renal failure due to polyarteritis nodosa with slow progression]. PMID- 2907060 TI - Vascular reactivities of isolated and perfused human ciliary arteries. AB - The vascular responses to 8 agents, norepinephrine (NE), phenylephrine (PHE), xylazine (XYL), tyramine (TYR), dopamine (DA), 5-hydroxytryptamine (5-HT), prostaglandin F2 alpha (PGF2 alpha) and KCl were examined in human posterior ciliary arteries (HPCAs) which were isolated and perfused with Tyrode's solution gassed with 95% O2 and 5% CO2 under a constant flow rate at 37 degrees C. The rank order for potency of vasoconstrictions was 5-HT greater than NE greater than PHE = PGF2 much greater than DA greater than TYR much greater than KCl. Responses to XYL were various but not significant. DA frequently induced a vasodilatation at smaller doses but a vasoconstriction at larger doses. Although their antagonists were not used in this study, it was suggested that 1) there are rich alpha-1 adrenoceptors and 5-HT receptors, 2) dopaminergic receptors exist in these arteries and 3) there are rich tyramine-sensitive catecholamine stores in nerve terminals. PMID- 2907061 TI - Synergism between calcium-mediated and cyclic AMP-mediated activation of chloride secretion in isolated guinea pig distal colon. AB - Synergistic effects of Ca2+-mediated secretagogues and cyclic AMP-mediated secretagogues on Cl- secretion by guinea pig distal colon were studied in vitro using Ussing chambers. Short-circuit current (Isc) and bidirectional fluxes of 22Na+ and 36Cl- were measured. Bethanechol (10(-4) M, a Ca2+-mediated secretagogue) caused an increase in Isc, which was enhanced 4-20 fold when the tissue was pretreated with prostaglandin E2 (10(-7)-10(-6) M), vasoactive intestinal polypeptide (5 x 10(-9)-10(-8) M) (cyclic AMP-mediated secretagogues), or 8-bromocyclic AMP (5 x 10(-4)-2 x 10(-3) M). Measurement of 36Cl flux showed that the increase in Isc in the presence of both 8-bromocyclic AMP and bethanechol resulted principally from increased Cl- secretion. On the other hand, the net absorptive flux of 22Na was not influenced under these conditions. Potentiation of the increase in Isc was also elicited by the combination of A23187 (5 x 10(-6) M) and 8-bromocyclic AMP (10(-3) M). The results are consistent with the notion that simultaneous activation of the cyclic AMP mediated and Ca2+-mediated systems produces a synergistic increase in colonic Cl- secretion. PMID- 2907062 TI - [The effect of drugs used during anesthesia and in the early postoperative period on gastric secretion]. PMID- 2907063 TI - [An interdisciplinary coordinated therapy concept exemplified by the Cornelia de Lange syndrome]. AB - This is a case-report of a male infant with typical signs of Cornelia de Lange syndrome. Coordination to subtype I or II of the disease is difficult, as somatical and intracerebral dysplasia (partial cerebellar aplasia) are combined. The etio-pathogenetic back-ground and the symptoms of the disorder will be discussed. Finally we point out to a omnidirectional therapeutic concept including several surgical and nonsurgical disciplines with the aim, to make life as easy as possible for these children. PMID- 2907064 TI - [Primary prevention of hemorrhage of esophageal varices by beta-blockade- generally indicated?]. PMID- 2907065 TI - [No Parkinsonian syndrome following acute paraquat poisoning]. AB - Paraquat structurally resembles N-methyl-4-phenyltetrahydropyridine (MPTP) and its metabolite 1-methyl-4-phenylpyridine (MPP+). MPTP and MPP+ are neurotoxic chemicals, which induce in exposed humans and in animal-models a Parkinson's disease. A high correlation between the incidence of Parkinson's disease and herbicide use in Canada led to the assumption that paraquat could give rise to parkinsonism. We have therefore carried out a follow-up study with patients having had dermal contact with paraquat or having swallowed paraquat accidentally or in a suicidal attempt. 7 patients took part in the study. Three of them had dermal contact. One had ingested paraquat by accident and three were survivors from suicidal paraquat intake. It was possible to exclude parkinsonism in all patients. One patient exhibited tardive dykinesia most likely due to a long term therapy with neuroleptic drugs. PMID- 2907066 TI - [Inhibition of intestinal leukotriene formation as a possible mechanism of action of sulfasalazine, 5-aminosalicylic acid and 4-aminosalicylic acid]. PMID- 2907067 TI - [Pharmacologic correction of microcirculatory disorders in recurrent peptic ulcer]. PMID- 2907068 TI - [Vascular permeability and erythrocyte hemostasis in patients with hemorrhagic fever and renal syndrome]. PMID- 2907069 TI - [Ultrasonic scanning of the kidneys in patients with hemorrhagic fever with renal syndrome and its complications]. PMID- 2907070 TI - [The importance of ultrasonography in detecting pathology of the kidneys during ambulatory observation of patients with hemorrhagic fever with renal syndrome]. PMID- 2907071 TI - [Pathophysiologic bases of the pharmacotherapy of peptic ulcer]. PMID- 2907072 TI - Interrelationships among self-reported alcohol intake, physiological indices and alcoholism screening measures. AB - The interrelationships among alcohol screening measures, self-reported drinking and laboratory markers of alcohol consumption were analyzed in a nonalcoholic sample. The results confirmed high interrelatedness among the MAST and two shorter versions derived from that scale. These measures showed little relationship to the CAGE, self-reported drinking and biochemical markers. Self reported drinking and the CAGE, however, were significantly correlated with these markers. One difference by gender was noted in the correlation between the CAGE and self-reported drink, with a stronger association found in men. The importance for investigators of considering the characteristics of these measures in light of their specific research questions is emphasized. PMID- 2907073 TI - A nonparametric method for evaluating results from laboratory antinociceptive tests. AB - A method is presented in which Cox's proportional hazards model, a survival analysis technique, is used to assess the results of hot-plate antinociceptive testing. The method appropriately handles censored data values and variable pretest latency times without making arbitrary assumptions about the distribution of the data. It may be used to characterize and compare dose-response curves or to examine the effect of agent or other treatment variables on the response. The technique is easily implemented using the SAS statistical software package. Due to the similar way in which data is obtained, we believe the method to be applicable to several other laboratory models of pain, including the tail-flick, tail-immersion, and paw-pressure (Randall-Selitto) assays. PMID- 2907074 TI - Localization of transglutaminase activity in type II epithelial cell cultures and elevation of enzyme activity in lungs of rats instilled with quartz. AB - Transglutaminase activity, assessed by the incorporation of [14C]-putrescine into N-acetylated dephosphorylated beta-casein, was not detectable in sonicates of alveolar macrophages and fibroblasts but was located in all preparations of rat alveolar type II cells. Enzyme activity was induced in these cells up to 7 days in vitro but not stimulated further by the direct addition of quartz to the cultures. Transglutaminase activity in whole lung sonicates increased significantly after short-term exposure to DQ-12 quartz. An increase in the numbers of type II cells and subsequent release of activated transglutaminase, concomitant with a quartz-induced elevation in lung calcium levels and potential protein substrates, is likely to lead to an increase in protein crosslinking both in the alveolar space and interstitium. PMID- 2907075 TI - [Neuroleptic-induced respiratory dyskinesia. Apropos of a case]. PMID- 2907076 TI - Exploratory behavior and the dual activity of some psychoactive drugs. Part IV. Neuroleptics. AB - Exploration is an essential, life-preserving component of animal higher nervous functions. The experiments presented here show that exploratory behavior may differ in relation to the subject's emotional baseline, and that accordingly, it is affected differently by various neuroleptics. PMID- 2907077 TI - [Acute manifestations in Crohn disease and ulcerative colitis. Conservative treatment of acute situations]. AB - Ulcerative colitis (UC) and Crohn's disease (CD) can lead to perforation, abscesses and peritonitis. In such cases conservative treatment should only be secondary to surgery, whereas intensive conservative treatment is needed from the very start in toxic megacolon. The decision to operate must be made within 24-48 h. Partial or complete intestinal obstruction is frequently encountered in CD patients if the ileum is involved. Prednisone treatment can sometimes reverse this condition when combined with parenteral nutrition. Treatment of acute exacerbations of UC and CD is essentially conservative and consists of salazosulfapyridine or 5-aminosalicylic acid and prednisone. PMID- 2907078 TI - [Cognitive-behavioral treatment of language disorders. Technic and clinical cases]. PMID- 2907079 TI - [Clotiazepam in psychiatric practice. Study with a daily high dosage per os]. PMID- 2907080 TI - Maximal exercise responses to acute and chronic beta-adrenergic blockade in healthy male subjects. AB - Conflicting data on the alterations in the maximal exercise response to beta blockade (BB) may be the result of differences in the length of time the subject has been on medication, i.e., hours vs days. The purpose of this study was to examine maximal exercise responses during acute and chronic administration of BB. Twenty-eight healthy males, 14 untrained (UT) and 14 involved in a personal training regimen (TR), performed maximal treadmill tests after 1 d and 9 d under three double-blind, randomized conditions: a placebo (PLAC), propranolol (PROP) 80 mg b.i.d., and atenolol (ATEN) 100 mg o.d. Maximal heart rate (HR), oxygen consumption (VO2), ventilation (VE), and treadmill time were significantly reduced by PROP and ATEN after an acute and chronic dose when compared to PLAC (P less than 0.05) in both groups of subjects. Maximal HR was decreased more after 1 d of BB than after 9 d of BB with both PROP and ATEN in the UT subjects and with PROP only in the TR group. VO2max, VEmax, and treadmill time were also less attenuated after 9 d of BB; however, this trend did not reach statistical significance. The nonselective beta blocker, PROP, caused greater reductions in VO2max compared to the selective beta blocker, ATEN, in both groups of subjects. These data indicate that, other than a small change in maximal HR, there is no difference in the exercise response to acute and chronic BB in normal and highly conditioned individuals. PMID- 2907081 TI - Monoclonal antibodies with fimbrial F1C, F12, F13, and F14 specificities obtained with fimbriae from E. coli 04:K12:H-. PMID- 2907082 TI - Monoclonal antibodies raised against Pap fimbriae recognize minor component(s) involved in receptor binding. AB - Pap fimbriae were purified from a recombinant strain and used for the production of monoclonal antibodies (MAbs). These MAbs were screened in a fimbriae ELISA with eight different P fimbriae as well as 1A and 1C fimbriae. Five MAbs were specific for Pap fimbriae whereas one MAb did react with Pap, F7(2) and F11 fimbriae. Previously, we described two F11 MAbs which also reacted with Pap, F7(2) and F11 fimbriae. In a whole bacteria ELISA it was shown that the MAbs, which recognized Pap, F7(2) and F11 fimbriae, reacted with recombinant strains which did not express Pap or F11 fimbriae, but still expressed the globoside binding properties. Not one of the five MAbs which are specific for Pap fimbriae reacted with these globoside binding recombinant strains. In a haemagglutination and adherence assay it was shown that only the MAbs which recognized the Pap, F7(2) and F11 fimbriae inhibited the adhesive properties of the globoside binding recombinant strain. Therefore it is concluded that in the present study MAbs are presented which recognize the minor components responsible for adhesion. PMID- 2907083 TI - Molecular cloning and characterization of the genetic determinant encoding CS3 fimbriae of enterotoxigenic Escherichia coli. AB - The genetic determinant encoding the synthesis and surface expression of CS3 fimbriae of colonization factor antigen II-(CFA/II-) positive enterotoxigenic Escherichia coli was cloned on a 5.1 kb HindIII DNA fragment in pBR322 from the wild-type plasmid pCS001 to yield the CS3+ plasmid pCS100. Subcloning of EcoRI fragments of 1.8 kb and 2.5 kb into vector plasmid pACYC184 and the isolation of a series of pCS100::Tn5 insertion mutants revealed that more than one cistron was involved in the synthesis and expression of CS3 fimbriae. Polypeptides of 94, 26, 24, 17 and 15 kDa were detected in E. coli minicells harbouring pCS100. In Western immunoblotting the 17 kDa and 15 kDa polypeptides reacted with specific anti-CS3 fimbriae serum. The 15 kDa polypeptide comigrated with the structural subunit of CS3 fimbriae. Inhibition of protein processing in minicells by ethanol confirmed that the 17 kDa polypeptide was the precursor form of the 15 kDa structural subunit. A physical map of the cloned DNA was constructed showing the location and direction of transcription of the genes for the 17 and 94 kDa polypeptides. Using the 5.1 kb HindIII fragment of pCS100 as a genetic probe for the CS3 determinant, Southern hybridization analysis of plasmid and total cellular DNA was performed in wild-type enterotoxigenic E. coli strains. PMID- 2907084 TI - Role of S- and common-type I-fimbriae of Escherichia coli in experimental upper and lower urinary tract infection. PMID- 2907085 TI - Chromosomal deletions and rearrangements cause coordinate loss of haemolysis, fimbriation and serum resistance in a uropathogenic strain of Escherichia coli. PMID- 2907086 TI - Immunosuppression and splenomegaly in Entamoeba histolytica infection in mice. AB - Intestinal amoebiasis caused by Entamoeba histolytica trophozoites in mice is accompanied by a depression in the ability of this host to develop an immune response to sheep red blood cells. The number of splenic plaque-forming cells was reduced in mice inoculated intracecally with 2.5 x 10(5) trophozoites at 15, 25, 40, 65 and 75 days after infection when compared with non-infected mice. It was found that there was no significant difference between the spleen weight of the infected and non-infected control animals at 5 and 10 days following infection. However, a significant increase in spleen weight was observed by 15 days of infection and the spleens remained enlarged until termination of the experiment at 75 days. Thus, there was an inverse correlation between the PFC response and the spleen weight of infected animals. PMID- 2907087 TI - Phase variation in Bordetella pertussis is accompanied by changes in DNA modification. AB - Pathogenic strains of Bordetella pertussis tend to undergo a phase variation process when propagated in vitro. The phase variants do not express part or all of the virulence factors of the pathogenic strain and are phenotypically stable. We have previously shown that variation involves a non-reversible, non-random process. In an attempt to characterize the molecular changes accompanying phase variation, chromosomal DNA, isolated from B. pertussis and its variants, was digested with a variety of restriction enzymes followed by agarose gel electrophoresis. While variant DNA was digested by all tested enzymes, pathogenic strain DNA was not digested by part of the enzymes, thus suggesting modification of the DNA at specific sites. DNA isolated from reversible, growth medium induced variants, demonstrated sensitivity to digestion identical to that of spontaneous, stable variants. Analysis of the restriction sequences of all the enzymes, which did not digest DNA from pathogenic strains, failed to reveal any common sequence known to be affected by methylation. HPLC and nearest-neighbor analysis showed a 2-fold increase in the level of DNA methylation in the pathogenic strain. It was concluded that (a) the chromosomal DNA in virulent strains of B. pertussis is protected against enzymatic digestion by an as yet unknown modification and (b) variation in B. pertussis may be caused by changes in the modification of the DNA rather than by mutation. PMID- 2907088 TI - Characterization of fimbrial subunits from Bordetella species. AB - Using antisera raised against serotype 2 and 3 fimbrial subunits from Bordetella pertussis, serologically related polypeptides were detected in Bordetella bronchiseptica, Bordetella parapertussis and Bordetella avium strains. The two B. pertussis fimbrial subunits, and three of the serologically related B. bronchiseptica polypeptides, were shown to be very similar in amino acid composition and N-terminal amino acid sequence. Homology was observed between the N-termini of these polypeptides, and fimbrial subunits from Escherichia coli, Haemophilus influenzae and Proteus mirabilis. A synthetic oligonucleotide probe, derived from the N-terminal sequence of the B. pertussis serotype 2 fimbrial subunit, was used to identify fimbrial genes in genomic Southern blots. The results suggested the presence of multiple fimbrial subunit genes in B. pertussis, B. bronchiseptica and B. parapertussis. The DNA probe was used to clone one of the three tentative fimbrial subunit genes detected in B. pertussis. PMID- 2907089 TI - [Correlation of mental fatigue due to work load and professional qualifications of physicians]. AB - The results presented in the paper refer to the relationship between physicians' professional qualifications and mental fatigue. It was that professional qualifications determining man's capabilities affect the level and structure of mental fatigue caused by work. Furthermore, it was assumed that this workload is multidimensional, and so its following five dimensions were singled out: mental difficulties, monotony, risk and responsibility, moral conflicts and dilemmas. The level of qualifications was measured by the length of employment and specialization and scientific degrees. The studies involved 10% of randomly selected physicians from all over Poland. The obtained results indicate that with increasing length of employment the workload due to moral dilemmas, risk and responsibility and mental difficulties, gets reduced; on the other hand, the load resulting from work monotony is increased. Also the specialization degree affects the workload caused by the risk, responsibility and moral dilemmas. Noticeable here is the trend towards a reduction in the workload with increasing specialization degrees. Instead, the higher the scientific degree the higher the sense of load due to risk and responsibility with simultaneous decrease in the load due to work monotony. PMID- 2907090 TI - Endocytosis-inducer adhesins produced by enteropathogenic serogroups of Escherichia coli participate on bacterial attachment to infant enterocytes. AB - Enteropathogenic E. coli (EPEC) infection of Hep-2 cells proceeds through bacterial attachment to cell surface and internalization of adhered bacteria. EPEC attachment is a prerequisite for cell infection and is mediated by adhesins that recognize carbohydrate-containing receptors on cell membrane. Such endocytosis-inducer adhesins (EIA) also promote EPEC binding to infant enterocytes, suggesting that EIA may have an important role on EPEC gastroenteritis. PMID- 2907091 TI - Kinin receptors. PMID- 2907092 TI - Depression of T cell-mediated immunity and enhancement of autoantibody production by natural infection with microorganisms in spontaneously hypertensive rats (SHR). AB - We studied the effects of breeding conditions on the development of immunological abnormalities in spontaneously hypertensive rats (SHR) with congenital T cell depression. The depression of T cell functions, the production of natural thymocytotoxic autoantibody (NTA), and the development of polyarteritis nodosa were more evident in SHR reared under a conventional (CV) environment than in specific-pathogen-free (SPF) SHR bred in a semi-barrier system. Enhancement of these immunologic abnormalities was also observed by the conventionalization of SPF-SHR. A high frequency of antibodies to mouse hepatitis virus (MHV), Sendai virus, and Mycoplasma pulmonis was detected in CV rat sera, whereas no antibodies were detected in SPF-SHR. The experimental infection of Sendai virus induced the enhancement of T cell depression and of NTA production in SPF-SHR. We interpret these results to mean that the natural infection of microorganisms causes an acceleration of immunologic abnormalities in SHR reared in a CV environment. PMID- 2907093 TI - Marked junctional bradycardia, prolonged QT interval and torsade de pointes in acute phenothiazine intoxication in a schizophrenic patient. A case report. PMID- 2907094 TI - Medullary thyroid carcinoma in children. PMID- 2907095 TI - H2 receptor antagonist usage in Missouri Medicaid recipients. PMID- 2907096 TI - Effects of transmitter antagonists on monopolar postsynaptic potentials. PMID- 2907097 TI - Behavioural effects of (+)-4-propyl-9-hydroxynaphthoxazine in primates rendered parkinsonian with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. AB - Three monkeys received a chronic intravenous course of 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) so as to produce a permanent parkinsonian syndrome. One primate was electively commenced on chronic levodopa therapy 6 weeks after the cessation of MPTP treatment. Four months following the termination of MPTP administration, the response to oral doses of the novel D-2 dopamine agonist (+) 4-propyl-9-hydroxynaphthoxazine (PHNO) was assessed in all animals using a clinical rating scale and automatic activity counters. PHNO was found to be a highly potent antiparkinsonian agent, completely reversing the symptoms of parkinsonism in a dose-dependent manner. Peak-dose dyskinesia was noted in 2 MPTP treated animals during trials with PHNO, but was more severe in the animal receiving chronic levodopa therapy. Response fluctuations such as 'end-of-dose' deterioration and the 'on-off' phenomenon were common to all 3 parkinsonian animals following PHNO. The anti-parkinsonian effect and frequency of treatment induced side-effects appeared to be similar with PHNO and levodopa. These results confirm the efficacy of PHNO as an anti-parkinsonian drug and link the production of dyskinesia with the D-2 dopamine receptor. PMID- 2907098 TI - Pre- and postsynaptic effects of p-tyramine and p-octopamine in the prostatic portion of the rat vas deferens. AB - The effect of p-tyramine and p-octopamine on the twitch responses of the prostatic portion of the rat vas deferens to electrical stimulation (0.025 Hz) were compared with the effects of noradrenaline. In tissues with normal monoamine oxidase (MAO) activity, the three amines increased the height and duration of the twitch contractions. When MAO activity was inhibited by pargyline (10 mumol/l), p tyramine and p-octopamine had mixed excitatory-inhibitory effects on the twitches, while noradrenaline had mostly excitatory effects along the whole range of concentrations assayed (0.158-15.8 mumol/l). Selective blockade of alpha 1- and alpha 2-adrenoceptors, by corynanthine and yohimbine, respectively, showed that the excitatory effect of the amines depended on the activation of alpha 1 adrenoceptor and that the inhibitory action was related to the activation of alpha 2-adrenoceptors. Pretreatment with reserpine (5 mg/kg, 24 h; 2.5 mg/kg, 2 h before the experiment) largely prevented the effects of p-tyramine and p octopamine, but the amines still modified the twitch responses to field stimulation. The addition of corynanthine and yohimbine to the bathing fluid revealed a considerable activation of alpha 1-excitatory and alpha 2-inhibitory adrenoceptors. Cocaine (10 mumol/l) did not antagonize, but rather enhanced the inhibitory effects of p-tyramine and p-octopamine in tissues with normal contents of noradrenaline. Moreover, cocaine did not antagonize the inhibition caused by p tyramine, and enhanced the inhibition induced by p-octopamine in the prostatic portion of the vasa deferentia from reserpine-pretreated animals. These results suggest that in this tissue, at least when MAO activity is inhibited, p-tyramine and p-octopamine behave similarly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2907099 TI - [3H]L-654,284 as a probe of the central alpha 2 adrenoceptor. AB - L-654,284 [2R, 12bS)-N-(1,3,4,6,7,12b-hexahydro-2H-benzo[b]-furo[2,3-a] quinolizin-2-yl)-N-methyl-2-hydroxyethanesulfonamide], a potent and selective antagonist of the alpha 2 adrenoceptor, was tritiated to high specific activity. Saturation binding to cell membrane suspensions obtained from calf cerebral cortex revealed a high affinity binding site (0.63 nM). Kinetics of association and dissociation were well represented by single exponential processes, and the equilibrium dissociation constant obtained from the ratio of rate constants agreed well with that found by saturation binding. A direct comparison of saturation binding revealed that the antagonist [3H]L-654,284 had roughly the same affinity for the alpha 2 adrenoceptor as the agonist [3H]clonidine and eight times the affinity of the antagonist [3H]rauwolscine. The maximum receptor densities of these radioligands were not significantly different. Competition assays with a series of compounds of known receptor affinity revealed that [3H]L 654,284 selectively binds to a site with all of the characteristics expected of the alpha 2 adrenoceptor. PMID- 2907101 TI - Only activated but not non-activated presynaptic alpha 2-autoreceptors interfere with neighbouring presynaptic receptor mechanisms. AB - Experiments were carried out in rabbit cerebrocortical slices in order to find out whether the attenuation by presynaptic alpha 2-autoreceptors of effects mediated by presynaptic opioid kappa- and adenosine A1-receptors requires activation of the alpha 2-receptors. The slices were preincubated with 3H noradrenaline and then superfused with medium containing desipramine 1 mumol/l. They were stimulated electrically either with single pulses or with trains of 32 pulses at 1 Hz. The overflow of tritium elicited by a single pulse amounted to 0.21% of the tritium content of the tissue. It was Ca2+-dependent and tetrodotoxin-sensitive and not changed by rauwolscine 1 mumol/l or yohimbine 0.3 mumol/l. Ethylketocyclazocine (EK; 0.1-10 nmol/l) and R-(-)-N6 phenylisopropyladenosine (PIA; 1-1,000 nmol/l) potently inhibited the overflow evoked by a single pulse, and their effects were not changed by yohimbine. - The overflow of tritium elicited by trains of 32 pulses at 1 Hz amounted to 0.92% of the tritium content of the tissue and was increased approximately fourfold by yohimbine 0.3 mumol/l. EK and PIA were less potent inhibitors than in the one pulse experiments. Yohimbine greatly enhanced the effects of EK and PIA. The enhancement was even more pronounced when the Ca2+ concentration in the medium was reduced in order to obtain a control tritium overflow similar to that evoked by 32 pulses in the absence of yohimbine. The results demonstrate that there is no alpha 2-adrenergic autoinhibition when noradrenaline release is elicited by a single pulse. Under these conditions, the non-activated presynaptic alpha 2 adrenoceptor does not interfere with presynaptic opioid kappa- and adenosine A1 receptor mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2907100 TI - Presynaptic alpha 2-adrenoceptor, opioid kappa-receptor and adenosine A1-receptor interactions on noradrenaline release in rabbit brain cortex. AB - The interaction of presynaptic, release-inhibiting alpha 2-adrenoceptors, opioid kappa-receptors and adenosine A1-receptors was studied in slices of the occipito parietal cortex of the rabbit. The slices were preincubated with 3H-noradrenaline and then superfused and stimulated electrically twice for 2 min each (S1, S2). The stimulation-evoked overflow of tritium was taken to reflect action potential evoked release of noradrenaline. One of two release-modulating compounds to be examined for interaction was kept in the medium throughout superfusion, the other one was added before S2. In many experiments, the stimulation parameters were adjusted (frequency 0.5-7 Hz; voltage drop 2-5 V/cm) in order to obtain similar reference release (S1) values despite the presence of the first release modulating compound. The selective kappa-receptor agonist ethylketocyclazocine (EK) attenuated markedly the release-inhibiting effects of the alpha 2 adrenoceptor-selective agonists clonidine and alpha-methylnoradrenaline as well as the release-facilitating effect of the alpha 2-adrenoceptor-selective antagonist yohimbine. The attenuation occurred both when the parameters of electrical stimulation were kept constant and when they were adjusted to obtain similar S1 release values. The selective A1-receptor agonist R-N6 phenylisopropyladenosine (PIA) also attenuated the effects of clonidine and yohimbine. Conversely, clonidine attenuated and yohimbine enhanced the release inhibiting effect of PIA. Yohimbine also enhanced the release-facilitating effect of the adenosine receptor antagonist 8-phenyltheophylline. Again, these changes occurred both at constant stimulation parameters and when stimulation parameters were adjusted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2907103 TI - [Biological markers of endogenous psychoses]. PMID- 2907102 TI - Antagonistic effects of alpha-adrenoceptor blocking agents on arrhythmias, enzyme release, and myocardial necrosis in isolated rat hearts with coronary occlusion and reperfusion. AB - In isolated perfused rat hearts reperfusion of the occluded left coronary artery led to arrhythmias, their severity depending on the duration of the foregoing period of myocardial ischaemia. Simultaneously, high activities of the myocardial enzyme creatine kinase (CK) were released into the perfusion fluid. Corynanthine, blocking mainly alpha 1-adrenoceptors, and rauwolscine, blocking mainly alpha 2 adrenoceptors, concentration-dependently antagonized the reperfusion-induced arrhythmias (3-30 mumol/l). The most severe kind of arrhythmia, i.e., ventricular fibrillation was completely prevented by 30 mumol/l of either drug. Also arrhythmias occurring already during the period of coronary occlusion were antagonized, as tested with corynanthine. The beta 1-adrenoceptor blocking agent metoprolol (1, and 10 mumol/l) had no effect at all against reperfusion arrhythmias, and the mainly alpha 1-adrenoceptor stimulating agent phenylephrine markedly increased the severity of these rhythm disturbances. The release of creatine kinase during the coronary reperfusion was significantly decreased by corynanthine, while the effect of rauwolscine was smaller and non-significant. Phenylephrine markedly increased the enzyme leakage from the myocardium. In all hearts the extent of the ischaemic and necrotic areas was determined. The percentage of the previously ischaemic area found necrotic at the end of the reperfusion, depended on the duration of the coronary occlusion. Corynanthine in a highly significant way decreased the area of myocardial necrosis, an effect obtained to some extent also with rauwolscine. The findings suggest that alpha adrenoceptor stimulation is involved in the genesis of arrhythmias and myocardial damage associated with myocardial ischaemia and reperfusion. Possible mechanisms of action of corynanthine and rauwolscine are discussed, especially in view of the interrelationship between alpha-adrenoceptors and slow calcium channels. PMID- 2907104 TI - [Schizophrenic psychosis in a patient with Gilles de la Tourette syndrome]. AB - A 36 year-old female patient with schizophrenia and Tourette syndrome is described. Clinical course, present neurological and psychopathological state, results of psychological testing, computed tomography and MR tomography of the skull, EEG and evoked potentials are reported. Results of neurochemical analysis of CSF and plasma are presented. Possible relationships between Tourette syndrome and schizophrenia are discussed with particular reference to neurochemical findings. PMID- 2907105 TI - Correlation among lipid peroxidation, brain energy metabolism and brain oedema in cerebral ischaemia. AB - In order to study the involvement of lipid peroxidation in the generation of ischaemic cell damage, sequential measurements were made on the chemiluminescence, energy metabolism, water content and the volume of Na+ and K+ in the cerebral cortex using a rat model for severe cerebral ischaemia. It was found that the amount of chemiluminescence increased due to ischaemia and increased further following recirculation. In chemiluminescence spectral analysis, peaks were found at 480, 520-530, 570, 620-640, 680-700 nm. It is thought that these wavelengths reflect the release of energy due to the reduction of active oxygens to more stable states during the breakdown of lipid hydroperoxide. The recovery of ATP in the 5 min ischaemic brain after reflow with ATP stopped at approx. 60% of the pre-ischaemia level, whereas the water content of the cortex showed an increase after 5 min of recirculation, and a gradual recovery thereafter for 30 min. There was a strong correlation between the increase in cortical water content after recirculation and the amount of chemiluminescence. It is concluded that causes of the ischaemic cerebral oedema include not only decreased activation of ATP-dependent Na+, K+-ATPase, but also functional changes in ion channels due to an increase in free radicals following recirculation. PMID- 2907106 TI - Evaluation of spinal evoked potentials: a model for assessment of spinal cord function in isolation. AB - Spinal evoked potentials were recorded from the dorsal columns of in vitro mouse hemicord preparations. The response of these potentials to different periods of hypoxia was studied. A decrease in amplitude of the potential to 50% and 10% of pre-hypoxia reference occurred after 3.19 +/- 1.36 and 7.3 +/- 2.97 min, respectively. Complete recovery of the potential was seen in specimens exposed to 5 and 10 min of hypoxia. Incomplete recovery occurred with exposure to longer periods of hypoxia. In preparations that remained isoelectric for less than 5 min total recovery was seen. PMID- 2907107 TI - Acute cerebral infarction and changes of regional cerebral blow flow (rCBF) following experimental middle cerebral artery (MCA) occlusion. AB - An unanaesthetized cat model of acute focal cerebral ischaemia has been established by the technique of transorbital snare ligature for middle cerebral artery (MCA) occlusion. The model was used to investigate the patterns of changes of regional cerebral blood flow (rCBF) for up to 16 h following MCA occlusion by the hydrogen clearance technique and to explore the correlation among changes of rCBF, neurological deficits, and pathological changes. The animals were divided into 2 groups according to the size of infarct which was identified by 2% triphenyl tetrazolium chloride (TTC) solution stain. Infarct larger than 10% of coronal section surface of ipsilateral hemisphere was found in 18 cats (Group A), and a smaller infarct was found in the remaining 7 cats (Group B). Between these 2 groups, there was a statistically significant difference in the average rCBF value of the ipsilateral MCA territory. The increasing grade of contralateral paralysis correlated well with the decreasing rCBF in the ipsilateral MCA territory, and the increasing grade of cerebral hemispheric swelling was directly proportional to the increasing grade of paralysis. Three patterns of changes of rCBF were observed: persistent severe ischaemia (15 cats, Group A); persistent mild to moderate ischaemia (7 cats, Group B); and immediate severe ischaemia followed by early post-ischaemic hyperaemia and death (3 cats, Group A). During the initial stage of ischaemia, a significant decrease in rCBF of the contralateral hemisphere was observed in both groups, however, in Group A rCBF gradually increased to preocclusion level, while Group B presented a further decrease in rCBF suggesting the occurrence of interhemispheric diaschisis. Thus, Group B appeared to take advantage of diaschisis during the late phase of infarct development, as well as the substantial collateral flow from the surrounding anterior and posterior cerebral artery territories. PMID- 2907108 TI - Long-term outcome of the management of ruptured intracranial aneurysm. Review of 328 consecutive patients treated over a period of 12 years. AB - From 1972 to 1984, 328 patients were admitted into the neurosurgical department for the treatment of a ruptured intracranial aneurysm, being clinically in grades 1 to 4. These patients were submitted to a deferred surgery protocol: 5.5% of the patients died before surgery, and 94.5% were actually operated upon. The follow up was at least over 1 yr, and up to 14 yr (average 3 yr 8 months). The long-term result was evaluated according to both the physical status of the patients and their activity resumption (professional, familial and social). This long-term result was compared to the immediate results, which had been evaluated either at the time of discharge or a few months later: 25.9% of the 328 patients were 'lost to view', and 74.1% were 'followed-up' (including preoperative and operative death). The immediate results were: death 17.7%, poor 7.3%, fair 9.1%, good 66.2%. The long-term results were evaluated as follows: poor 7%, fair (independent but with emotional or psychological difficulties) 14.8%, good (fully independent) 55.1%. The long-term activity resumption (ability to work) was: normal 46.5%, lesser level of work 7.8%, unable to work 20.5%. Out of the patients with a good and fair immediate result, only 66.5% resumed their previous occupation: 21.2% of these patients did not resume their previous occupation due to psychological or emotional disturbances. PMID- 2907109 TI - The third nerve transection and regeneration in rats with preliminary results on the sixth nerve transection and regeneration in guinea pigs. AB - The relationship between the phenomenon of the nonselective reinnervation and the functional recovery after section and repair of the highly organized third cranial nerve motor system in rats was studied. The same relationship after section and repair of the more simply organized sixth cranial nerve motor system in guinea pigs is presented as preliminary results. Anatomical demonstration of nonselective reinnervation was obtained by injecting horseradish peroxidase (HRP) into the extraocular muscles. A bilateral reinnervation of previously ipsilateral innervated muscles both in the third and the sixth nerve was interpreted as a plastic response of the brain stem neurons to the nerve injury. Functional recovery, evaluated by measuring with an infrared light technique the horizontal and vertical vestibulo-ocular reflexes, was excellent for the rectus lateralis muscle while it was relatively poor i.e. partial for the muscles depending on the third nerve. These data suggest that one of the most important factors influencing the functional recovery after section and repair of a peripheral nerve is the complexity of the nerve motor system organization. PMID- 2907110 TI - Regional cerebral blood flow (rCBF) pattern analysis corresponds with albumin extravasation in experimental cerebral ischaemia. AB - The possibility of the evaluation of ischemia solely by the momentary values of regional cerebral blood flow (rCBF) was investigated. Ischaemic damage was evaluated histopathologically and by observing albumin extravasation. Unilateral carotid clippings were performed for 1 h and the gerbils evaluated with regard to the length of recirculation time. In animals without a recirculation period, the degree of damage could be explained by the rCBF reduction ratio during clipping. However, in cases with reperfusion periods, 5 animals showed an almost complete disappearance of rCBF during clipping, but albumin extravasation was seen in 1 case only. Thus, the discordance between the rCBF reduction ratio and the abnormal permeability was considerable in reperfused animals. The post-ischaemic rCBF pattern was classified into 3 types, the 'post-ischaemic hyperperfusion type', the 'post-ischaemic hypoperfusion type' and the 'post-ischaemic normoperfusion type'. In the first two types, the albumin extravasation was positive in 10/10 cases, and in the third type, in only 1/20. Therefore, the post ischaemic rCBF pattern was thought to correlate well with ischaemic damage in the reperfused cases. The rCBF changes momentarily and the pattern analysis of the rCBF, particularly in the post-ischaemic phase, appeared to be important. PMID- 2907111 TI - Effects of methyl prednisolone, dimethyl sulphoxide and naloxone in experimental spinal cord injuries in rats. AB - The effects of methyl prednisolone (MPD), dimethyl sulphoxide (DMSO), and naloxone were examined in 38 albino rats after making an impact spinal cord injury on the midthoracic segments with a modified Allen's weight dropping trauma method. Somatosensorial evoked potentials (SEPs) were recorded before and 12 h and 14 d after the injury from epidurally inserted electrodes on the parietal cortex with sciatic nerve stimulations. Lower extremity motor functions of the animals were also examined. It may be concluded that in this study model, DMSO has a moderate effect which can be demonstrated clinically and through SEPs. Naloxone has no effect on the clinical outcome but causes reasonable improvement electrophysiologically. PMID- 2907112 TI - Thyrotropin releasing hormone uptake into serum and cerebrospinal fluid following intravenous or subcutaneous administration. AB - Intravenous thyrotropin releasing hormone (TRH) was administered to 6 amyotrophic lateral sclerosis (ALS) patients at the dose rate of 10 mg/kg. Blood samples were obtained prior to and at 10, 20, 40, 60, and 120 min during the TRH infusions. Lumbar punctures were performed at 90 min following the start of infusion. The mean serum TRH concentration rose from 0.03 +/- 0.02 (SD) to 17 +/- 2 ng/ml by 60 min and remained constant to 120 min. The mean CSF TRH concentration rose 10-fold from 0.02 +/- 0.01 to 0.2 +/- 0.02 ng/ml at 90 min and increased further to 0.5 +/- 0.2 ng/ml at 120 min. Subcutaneous TRH was administered to 4 ALS patients at 2.5 mg/kg and to 5 ALS patients at 5.0 mg/kg. The mean serum TRH concentration increased to 1.4 +/- 0.6 ng/ml (2.5 mg/kg) and 3.2 +/- 1.1 ng/ml (5.0 mg/kg) by 60 min. The mean CSF TRH concentration at 60 min increased to 0.3 +/- 0.08 ng/ml following 2.5 mg/kg TRH and 0.8 +/- 0.04 ng/ml following 5.0 mg/kg TRH. TRH entry into the CSF is comparable following subcutaneous or intravenous administration. PMID- 2907113 TI - Haemodynamic changes in arteriovenous malformations induced by superselective embolization: transcranial Doppler evaluation. AB - To reduce the intraoperative and postoperative complications in patients who suffer intracerebral arteriovenous malformations (AVM's), the slow reduction of the shunt flow to a brain perfusion flow has been tried by the use of several methods: microsurgical techniques, selective and superselective embolization, intraoperative embolization, staged operation. The risk of re-bleeding and intraoperative oedema increases in AVM's with two or more feeders. Our policy was to exclude such AVM's by primary superselective embolization. If there was only a small residual angioma, we tried to remove this by microsurgical techniques. The haemodynamics in AVM's could be examined by measuring the blood flow velocities in the feeding arteries and in the other parts of the circle of Willis by transcranial Doppler sonography (TCD). Signs of haemodynamic effective embolization could be measured by the reduction of flow velocities. After exclusion of an AVM the velocities in the brain and feeding arteries decreased to below normal values in the first days after the operation. In the feeding arteries this was due to the fact that the arteries were enlarged so that the velocity must be decreased when there was normal volume flow. The combination of superselective angiography and microsurgical resection of the residual angioma seemed to be the best way to treat AVM's which are fed by more than two arteries and which are 3 or more cm in diameter. TCD investigations were used to measure the haemodynamic changes before and after angioma superselective embolization and microsurgical operation. PMID- 2907114 TI - Penumbra around chronic cerebral infarction? AB - In a series of 13 patients with cerebrovascular occlusive disease regional cerebral blood flow (rCBF) measurements (two-dimensional intravenous 133Xe clearance method) and quantitative EEG analysis (sensorimotor rhythms) as well as electronic measurement of handforce were performed before and during intravenous infusion of 1 microgram kg/min of one of the lipophilic dihydropyridine calcium channel blocker nimodipine (Nimotop). The aim of the study was to test the hypothesis of the existence of hypoperfusion (ischaemic penumbra) in the surroundings of chronic cerebral infarcts. All 3 parameters improved in one patient. Sensorimotor rhythms increased in 5 patients, rCBF in 3. EEG and rCBF improved in 2 patients. In 3 instances, a redistribution of rCBF in favour of the peri-infarct zone was noted (significant increase of rCBF from 35 +/- 2 SEM to 53 +/- 4 ml/100 g/min (p less than 0.01), whereas rCBF fell from 61 +/- 5 to 46 +/- 2 ml/100 g/min on a collimator remote from the infarct but in the infarcted hemisphere. The parallel improvement of rCBF and EEG in brain regions surrounding chronic infarcts in 3 patients was interpreted as functional improvement as a consequence of nimodipine-induced normalization of peri-infarct hypoperfusion, i.e. reversal of flow-dependent neuronal silence and/or dysfunction. PMID- 2907115 TI - Antagonism of dermorphin-induced catalepsy with naloxone, TRH-analog CG3703 and the benzodiazepine antagonist, Ro 15-1788. AB - Intracerebroventricular (i.c.v.) administration of the highly selective opiate mu receptor agonist, dermorphin, produced dose-dependent catalepsy in conscious rats. The cataleptic effect of dermorphin was abolished by pretreatment (intraperitoneal, i.p.) with the opiate-antagonist naloxone (5 mg/kg), thyrotropin-releasing hormone analog CG3703 (1 mg/kg) or the benzodiazepine antagonist Ro 15-1788 (5 mg/kg) whereas pretreatment with the benzodiazepine alprazolam (1 mg/kg) potentiated the cataleptic effect of dermorphin. When given to cataleptic rats, naloxone and CG3703, but not Ro 15-1788, reversed the dermorphin-induced catalepsy. The data suggest an involvement of benzodiazepine receptors in the induction of catalepsy mediated by opioid mu-receptors. Other opioid-modulating neuronal systems, antagonized by CG3703, may be involved in maintaining the dermorphin-induced cataleptic state. PMID- 2907116 TI - Effects of ipsapirone on the behaviour of mice during social encounters. AB - Behavioural effects of ipsapirone at 30 min after intraperitoneal injections of 0.3 mg/kg and 3.0 mg/kg to adult male mice, were examined by ethopharmacological procedures in 7 min encounters with untreated isolated males in a neutral cage. Control males received intraperitoneal injections of physiological saline. The frequency and duration of aggressive behaviour were less in drug-treated than in saline-injected males. The occurrence of distance ambivalence and defensive ambivalence also were found to be significantly decreased by ipsapirone when the results from all drug-treated animals were compared with those of controls. The drug, at 3 mg/kg, induced hypothermia and also enhanced the minor behavioural acts of "head jerk" and "scratch". Partners to the drug-treated mice showed a decrease in the occurrence of offensive ambivalence and of the element "rattle". The present findings show that ipsapirone reduced conflict-related behaviour in mice, in association with its anti-aggressive properties. PMID- 2907117 TI - Interaction of some atypical antidepressants and adrenoceptor antagonists with imipramine: a behavioural study with isoprenaline-induced drinking. AB - The systemic administration of isoprenaline to rats produced a dose-dependent increase in drinking which was antagonized by propranolol. While oral administration of the antidepressant, imipramine, alone had no significant effect on this response, the increase was significantly inhibited by administration of imipramine together with each of the following drugs over a period of 4 days: bupropion (21.0 mg/kg/day, p.o.), a selective inhibitor of the uptake of dopamine and nomifensine (10.6 mg/kg/day, p.o.), a relatively selective dopamine and a blocker of the uptake of noradrenaline. Similarly, the combination of the selective alpha 1-adrenoceptor antagonist, prazosin (2.37 mg/kg/day, p.o.); the selective alpha 2-adrenoceptor antagonist, yohimbine (2.38 mg/kg/day, p.o.) or the non-selective alpha-adrenoceptor blocker, phentolamine (4.65 mg/kg/day, p.o.) with imipramine caused a significant inhibition of the isoprenaline-induced drinking. It is concluded that fast desensitization of central beta-adrenoceptors in the rat can be produced after the oral subacute simultaneous administration of imipramine with alpha-adrenoceptor antagonists or atypical antidepressants, such as nomifensine or bupropion. PMID- 2907118 TI - Release of prostaglandin E2 from brain of cat: II. In vivo studies on the effects of adrenergic, cholinergic and dopaminergic agonists and antagonists. AB - This study examined the effect of several neurotransmitters, receptor agonists and antagonists on the release of prostaglandin E2 (PGE2) from brain. Levels of PGE2 were measured in consecutive 30-min samples, collected from ventriculocisternal perfusions (100 microliters/min) in chloralose-urethanized cats, before, during and after the addition of carbachol, norepinephrine (NE) and dopamine (DA). Samples were submitted to acid organic extraction and radioimmunoassay (RIA) with a specific antibody. Displacement curves of ligand binding with control and stimulated samples were parallel to those observed with PGE2. The addition of carbachol (10(-4) M) to the perfusate resulted in a significant increase in the levels of PGE2 from 600 +/- 259 pg PGE2/min during the control period up to 1306 +/- 429 pg PGE2/min during the perfusion (P less than 0.02). Though NE (10(-3) M) and isoproterenol (10(-3) M, beta) were without effect, methoxamine (10(-3) M, alpha 1), but not ST-91 (an alpha 2-agonist), produced an increase in secretion of PGE2. This increase was blocked by phentolamine (10(-3) M). The addition of DA (10(-4) M) produced a fall from control levels of 642 +/- 185 pg PGE2/min to 290 +/- 101 pg PGE2/min (P less than 0.02). These results suggest that the central activation of selected populations of receptors will alter basal levels of PGE2 in the extracellular space. PMID- 2907119 TI - Release of immunoreactive somatostatin in the spinal dorsal horn of the cat. AB - Antibody microprobes were used to investigate the possible release of immunoreactive somatostatin (irSS) within the lumbar spinal cord of anaesthetized cats. A basal release of irSS was detected in the region of the substantia gelatinosa of the dorsal horn. By comparison with in vitro standards the concentration of SS detected in this region was estimated at 10(-7) M. This release of irSS was not significantly altered by electrical stimulation of large myelinated primary afferent fibres but was increased when unmyelinated afferents were additionally stimulated. Release of irSS was also detected at the spinal cord surface. The results support a role for somatostatin in nociceptive transmission in the spinal cord. PMID- 2907120 TI - Identification of 3H-bradykinin binding sites in PC-12 cells and brain. AB - 3H-Bradykinin binding sites with the characteristics of receptors were identified in homogenates of bovine hippocampus and PC-12 cells. The characteristics of the binding were similar in both types of tissue and paralleled those of the B2 bradykinin receptor. Following exposure to nerve growth factor for 72 hours, the number of BK binding sites in PC-12 cells significantly increased, but other characteristics of the binding remained unchanged. PMID- 2907121 TI - Inhibition by MIF-I of alpha-MSH induced increase of intraocular pressure and miosis in rabbits. AB - The effects of intracameral (i.c.) administration of MIF-I on the ocular response to alpha-MSH were tested in rabbits. In confirmation of previous studies, i.c. alpha-MSH significantly increased intraocular pressure (IOP) and reduced pupillary diameter (PD). Concomitant administration of alpha-MSH and MIF-I antagonized both the IOP increase and miosis induced by alpha-MSH. Aqueous humor (AH) dynamics studies revealed that alpha-MSH increases IOP, possibly, by decreasing AH outflow. The decreased AH outflow induced by alpha-MSH was antagonized by concurrent administration of MIF-I and alpha-MSH. MIF-I did not affect IOP or PD when administered alone. These results add more support for a role of alpha-MSH in ocular function, and suggest that the ocular response to alpha-MSH may be subject to inhibitory control by MIF-I. PMID- 2907122 TI - Effects of intracerebroventricularly administered somatostatin on passive avoidance, shuttle-box behaviour and open-field activity in rats. AB - Behavioural effects of somatostatin after intracerebroventricular (icv) administration have been investigated in male rats. In a passive avoidance learning test, somatostatin (1 microgram), given 30 min before the learning session, increased the avoidance latency at 24 h, but not at 48 h, after the injection, when compared to a 10 micrograms treated group. However, compared to a saline treated group, somatostatin (0.01, 0.1, 1, or 10 micrograms) did not significantly influence the avoidance latency. In a shuttle box experiment somatostatin (1 microgram) facilitated the learning process. In an open-field behaviour test, immediately after the 24 h passive avoidance test, 10 micrograms of the peptide decreased the rearing activity without influencing other open field behaviours, like locomotion, grooming and defecation. In a second open field experiment somatostatin (1 microgram), given 30 min prior to the test, similarly as in the shuttle box learning experiment, increased the locomotion of the animals. These data suggest that somatostatin influences both the passive avoidance and shuttle box behaviours. The peptide-induced motor performance of the animals may play an important role in influencing the responses observed in these behavioural tests. PMID- 2907124 TI - [Use of DNA restriction fragment length polymorphisms in the diagnosis of genetically determined diseases]. PMID- 2907123 TI - [Slow acetylation phenotype as a risk factor in patients with laryngeal cancer]. PMID- 2907125 TI - [Results of the treatment of ulcerative colitis during the past 28 years]. PMID- 2907126 TI - [Kinetics of the changes in the proxybarbital level after its oral and intravenous administration in a monocompartmental model in humans]. PMID- 2907127 TI - [Peripheral neuron damage in periarteritis nodosa: diagnostic problems]. PMID- 2907128 TI - Cimetidine-diazepam interaction in the four-plate test. AB - The study on the synergism of cimetidine with the central anti-anxiety action of diazepam in the four-plate test revealed that cimetidine evidently potentiates the anti-anxiety action of diazepam. PMID- 2907129 TI - Frequency-dependence of 3H-noradrenaline release from rabbit pulmonary artery: effect of alpha-adrenoceptor antagonists and inhibitors of transmitter inactivation. AB - The aim of this study was to examine the modulating role of presynaptic alpha 2 adrenoceptors on transmitter release from vascular sympathetic neurones. This was done by examining the influence of removal of inactivation pathways on the effect of alpha-adrenoceptor antagonists on the release of transmitter from noradrenergic neurones. The rabbit main pulmonary artery preloaded with 3H noradrenaline (3H-NA) was used. The artery was stimulated with 300 pulses at various frequencies (1, 3, 10 and 30 Hz). Pargyline (3 x 10(-4) M) increased the stimulation-evoked 3H-overflow at 1 and 3 Hz and decreased it at 30 Hz. U-0521 (3',4'-dihydroxy-2-methylpropiophenone; 3 x 10(-6) M) enhanced the overflow at 1 Hz and had no effect at 3-30 Hz. Corticosterone (4 x 10(-5) M) did not alter the stimulation-evoked 3H-overflow at 1-30 Hz. Cocaine (3 x 10(-6) M) enhanced the 3H overflow slightly at 1-30 Hz. At 3 x 10(-5) M, cocaine enhanced 3H-overflow at 1 Hz and reduced it at 30 Hz. Neither corticosterone (4 x 10(-5) M) nor propranolol (10(-7) M) modified this effect of cocaine. Propranolol (10(-7) M) alone decreased the 3H-overflow at 30 Hz and had no effect at 1-10 Hz. Phenoxybenzamine (10(-6) M) and chlorpromazine (3 x 10(-6) M) potentiated the stimulation-evoked 3H-overflow at 1-30 Hz.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2907130 TI - Assays for mammalian tyrosinase: a comparative study. AB - This work describes a comparative study of the tyrosinase activity determined using three methods which are the most extensively employed; two radiometric assays using L-tyrosine as substrate (tyrosine hydroxylase and melanin formation activities) and one spectrophotometric assay using L-dopa (dopa oxidase activity). The three methods were simultaneously employed to measure the activities of the soluble, melanosomal, and microsomal tyrosinase isozymes from Harding-Passey mouse melanoma through their purification processes. The aim of this study was to find any correlation among the tyrosinase activities measured by the three different assays and to determine whether that correlation varied with the isozyme and its degree of purification. The results show that mammalian tyrosinase has a greater turnover number for L-dopa than for L-tyrosine. Thus, enzyme activity, expressed as mumol of substrate transformed per min, is higher in assays using L-dopa as substrate than those using L-tyrosine. Moreover, the percentage of hydroxylated L-tyrosine that is converted into melanin is low and is affected by several factors, apparently decreasing the tyrosinase activity measured by the melanin formation assay. Bearing these considerations in mind, average interassay factors are proposed. Their values are 10 to transform melanin formation into tyrosine hydroxylase activity, 100 to transform tyrosine hydroxylase into dopa oxidase activity, and 1,000 to transform melanin formation into dopa oxidase activity. Variations in these values due to the presence in the tyrosinase preparations of either inhibitors or regulatory factors in melanogenesis independent of tyrosinase are also discussed. PMID- 2907131 TI - Screening for alcoholism. AB - Alcoholism is one of the largest public health problems of the nation and is a significant cofactor in such ubiquitous diseases as hypertension, developmental abnormalities, heart failure, liver failure, and many other conditions. The cost to the nation's health is immense. One strategy for reducing morbidity and cost has been to establish methods for screening in order to increase recognition rates leading to increased rates of therapeutic intervention. In this article, the rationale for two methods of alcohol screening, brief interviews and biological markers of excessive drinking, the relevant statistical issues bearing on this problem, and the current research on screening exams are reviewed and summarized. Finally, some of the newer approaches toward alcoholism screening as well as the consequences to the medical care system should alcohol screening eventuate on a large scale are briefly described. PMID- 2907132 TI - [The multiple endocrine neoplasm type-IIb syndrome]. PMID- 2907133 TI - Protein engineering of cytochrome c by semisynthesis: substitutions at glutamic acid 66. AB - We have used protein semisynthesis to prepare four analogues of horse cytochrome c, in which the glutamic acid residue at position 66 has been removed and replaced by norvaline, glutamine, lysine and, as a methodological control, glutamic acid. This residue is quite strongly conserved in mitochondrial cytochrome c, and forms part of a cluster of acidic residues that occurs in all cytochromes c but whose function is obscure. Comparative studies of the physical and biochemical properties of the analogues have now disclosed two specific roles for Glu66 in the protein. It contributes significantly to the stabilization of the active conformation of the protein, probably by salt bridge formation, and it appears to participate in the redox-state-dependent ATP-binding site of cytochrome c. Our results also support two general views of the role of surface charged residues in cytochrome c, namely that their disposition influences both redox potential, through the electrostatic field felt at the redox centre, and the kinetics of electron transfer, through the dipole moment they generate. PMID- 2907134 TI - Predicted secondary structure and membrane topology of the scrapie prion protein. AB - The integral membrane sialoglycoprotein PrPSc is the only identifiable component of the scrapie prion. Scrapie in animals and Creutzfeldt-Jakob disease in humans are transmissible, degenerative neurological diseases caused by prions. Standard predictive strategies have been used to analyze the secondary structure of the prion protein in conjunction with Fourier analysis of the primary sequence hydrophobicities to detect potential amphipathic regions. Several hydrophobic segments, a proline- and glycine-rich repeat region and putative glycosylation sites are incorporated into a model for the integral membrane topology of PrP. The complete amino acid sequences of the hamster, human and mouse prion proteins are compared and the effects of residue substitutions upon the predicted conformation of the polypeptide chain are discussed. While PrP has a unique primary structure, its predicted secondary structure shares some interesting features with the serum amyloid A proteins. These proteins undergo a post translational modification to yield amyloid A, molecules that share with PrP the ability to polymerize into birefringent filaments. Our analyses may explain some experimental observations on PrP, and suggest further studies on the properties of the scrapie and cellular PrP isoforms. PMID- 2907135 TI - Filamentous proteins in Alzheimer's disease: new insights through molecular biology. AB - Recent advances in the study of the neurofibrillary tangles (NFT), neuritic plaques (NP), and cerebrovascular amyloid found in the brain of Alzheimer's disease (AD) victims have greatly expanded our understanding of the molecular biology of this disease. Paired helical filaments (PHF) are the primary intracellular filamentous deposit. They appear to be distinct from normal cytoskeletal proteins, but they do contain a significant component of a microtubule-associated protein called 'tau'. Amyloid fibrils make up the extracellular filamentous deposits in AD. Amyloid fibrils are composed of a small protein of about 43 amino acids which has been sequenced. Some investigators suggest PHF are composed of this same protein, but this remains debatable. Molecular genetic studies have shown that a gene which codes for a larger protein containing the sequence of the 'beta-amyloid protein' exists in many tissues and in many species. Interestingly, this gene is located on chromosome 21 which is also the location of the familial AD gene, but these 2 genes are distinct. Several hypotheses exist on the origin of these abnormal deposits and range from neuronal origin to synthesis outside of the CNS with transportation via the blood. The implications of these recent advances are great and include the possibility of accurate and early antemortem diagnostic tests for AD, as well as therapeutic manipulation of the synthesis, deposition, or removal of these filamentous proteins. PMID- 2907136 TI - A unified biosocial theory of personality and its role in the development of anxiety states: a reply to commentaries. AB - The comments by Gray, Gelder, Liebowitz, Eysenck, Nurnberger, Roy and Linnoila are discussed. Most of the recommendations in the comments have already been carried out and the others are under way. Specifically, practical assessment instruments have been developed, and their psychometric properties are under investigation. Explicit criteria for systematic diagnosis of personality disorders have been developed. Longitudinal studies have been carried out to evaluate the predictive validity of the scales. Empirical tests have confirmed the predicted relationship between novelty seeking and somatic anxiety, as well as between harm avoidance and cognitive anxiety. A more detailed model of the underlying neural processes has been described. Growing evidence of norepinephrine's role in reward dependence has been reported. Finally, a more comprehensive learning model has been developed that can account for both the higher-order and the lower-order factor structure of personality in terms of specific stimulus-response characteristics. Several commentators have provided additional evidence supporting the predicted role of the monoamines in modulating personality and learning. Finally, predictions from my model about pain sensitivity, stimulus intensity modulation, and the factor structure of personality have been compared to those of Gray and Eysenck. The predictions are confirmed for my model, but not those of Gray or Eysenck. PMID- 2907137 TI - The Claude Bernard lecture, 1987. Embryonic chimeras: a tool for studying the development of the nervous and immune systems. AB - Chimeras have been constructed in the avian embryo following the observation of the particular structure of the interphase nucleus in the Japanese quail (Coturnix coturnix japonica). In all embryonic and adult cell types of this species a large amount of heterochromatin is associated with the nucleolus, making quail cells readily distinguishable from those of the chick where the constitutive heterochromatin is evenly dispersed in the nucleus. These structural differences have been used to devise a cell-marking technique through which cell migrations and cell interactions during embryogenesis can be followed in the embryo in ovo by grafting quail cells into chick embryos or vice versa. This method was applied to the ontogeny of the neural crest and of the immune system. Recently quail-chick chimeras have been allowed to hatch and the immunological status of the embryonic grafts after birth scrutinized. Xenogeneic tissue grafts made in the embryo are rejected after birth with a more or less prolonged delay according to the nature of the graft. However, rejection can be prevented and a permanent state of tolerance induced for the embryonic tissue grafts by isotopically implanting the thymic epithelium from the same quail donor. PMID- 2907138 TI - The effect of Lambert-Eaton myasthenic syndrome antibody on slow action potentials in mouse cardiac ventricle. AB - Immunoglobulin G (IgG) from Lambert-Eaton myasthenic syndrome (LEMS) patients acts at motor nerve terminal Ca2+ channels. It was injected into mice to investigate effects on cardiac Ca2+ channels. Intracellular recordings were made of slow action potentials in right ventricular muscle cells in the presence of high K+ concentrations and isoprenaline (1 microM). Reduction in Ca2+ concentration reduced the rate of rise and amplitude, but not the duration, of slow action potentials whereas verapamil (1 microM) blocked them. They were not blocked by tetrodotoxin (10 microM), and 4-aminopyridine (1 mM) prolonged the decay phase without affecting the rate of rise and amplitude. The rate of rise, amplitude and duration of slow action potentials were not affected by LEMS IgG. These results show that LEMS IgG does not act on Ca2+ channel currents that underlie slow action potentials in mouse ventricles, suggesting antigenic differences between Ca2+ channels at motor nerve terminals and heart. PMID- 2907139 TI - A review of early (Silurian and Devonian) vertebrate biogeography and biostratigraphy of China. AB - A review of the vertebrates within the Silurian and Devonian of China suggests a more detailed picture of palaeobiogeographical distribution than previously possible. Although the localities are commonly in rocks of continental aspect, marine formations also are present nearby. Of over 60 agnathan and fish genera known, only 5 placoderms (Givetian-Famennian) are cosmopolitan. Endemic patterns of distribution within China relate to the well-known tectonic (basinal or platformal) regions. Silurian vertebrates occur in southern, eastern and western parts of the country and are familiar from horizons as low as Llandovery. Devonian vertebrates include a wide range of endemic forms, which provide evidence of more than six distinct biostratigraphic assemblages in South China and five biogeographical realms. PMID- 2907140 TI - Stretch-activated ion channels modulate the resting membrane potential during early embryogenesis. AB - By using the patch-clamp technique, stretch-activated ionic channels were found in the membrane of cleaving freshwater fish embryos at the early stages of embryogenesis (2-256 cells). The application of negative pressure to the pipette increased the frequency of activation and the duration of bursts. This type of channel has a preferential K+ selectivity. When bathed on both membrane surfaces with 140 mM KCl the channel conductance was 71 pS. The kinetic behaviour did not depend markedly on either membrane potential (in the range from -70 to +70 mV) or calcium concentration on the cytoplasmic side of the membrane. On continuous recording, the probability of the channel being open was found to change periodically over a 5- to 20-fold range for different cells. These variations correlated with changes in resting potential and membrane conductance during the cell cycle. These results suggest that the oscillation of resting potential within the cell cycle is associated with the operation of stretch-activated ion channels. PMID- 2907141 TI - The Ferrier lecture, 1986. The actions of parasympathetic and sympathetic nerves in human micturition, erection and seminal emission, and their restoration in paraplegic patients by implanted electrical stimulators. AB - Implants that stimulate the S2, S3 and S4 anterior roots improve micturition, defaecation and penile erection in many patients with spinal-cord injuries. The posterior rhizotomy that is commonly done at the same time usually cures their urinary incontinence, and may greatly improve bladder compliance. Implants that stimulate the hypogastric plexus allow semen to be obtained easily from some men with spinal injuries who cannot ejaculate, and may allow an implant-driven erection. A little new knowledge about the neurophysiology of the pelvic organs has come from studying the performance of these implants. PMID- 2907142 TI - The Leeuwenhoek lecture, 1987. Towards an understanding of gene switching in Streptomyces, the basis of sporulation and antibiotic production. AB - Streptomycetes are soil bacteria that differ from the genetically well-known Escherichia coli in two striking characteristics. (1) Instead of consisting of an alternation of growth and fission of morphologically simple, undifferentiated rods, the streptomycete life cycle involves the formation of a system of elongated, branching hyphae which, after a period of vegetative growth, respond to specific signals by producing specialized spore-bearing structures. (2) The streptomycetes produce an unrivalled range of chemically diverse 'secondary metabolites', which we recognize as antibiotics, herbicides and pharmacologically active molecules, and which presumably play an important role in the streptomycete life cycle in nature. This 'physiological' differentiation is often temporally associated with the morphological differentiation of sporulation and there are common elements in the regulation of the two sets of processes. In the model system provided by Streptomyces coelicolor A3(2), the isolation of several whole clusters of linked antibiotic biosynthetic pathway genes, and some key regulatory genes involved in sporulation, has made it possible to study the basis for the switching on and off of particular sets of genes during morphological and 'physiological' differentiation. Genetic analysis clearly reveals a regulatory cascade operating at several levels in a 'physiological' branch of the differentiation control system. At the lowest level, within individual clusters of antibiotic biosynthesis genes are genes with a role as activators of the structural genes for the pathway enzymes, and also resistance genes. It is attractive to speculate that the latter play a dual role: protecting the organism from self-destruction by its own potentially lethal product, and forming an essential component of a regulatory circuit that activates the biosynthetic genes, thus ensuring that resistance is established before any antibiotic is made. A next higher level of regulation is revealed by the isolation of mutations in a gene (afsB) required for expression (probably at the level of transcription) of all five known secondary metabolic pathways in the organism. At a higher level still, the bldA gene, whose product seems to be a tRNA essential to translate the rare (in high [G + C] Streptomyces DNA) TTA leucine codon, controls or influences the whole gamut of morphological and 'physiological' differentiation, because bldA mutants fail to produce either secondary metabolites or aerial mycelium and spores, while growing normally in the vegetative phase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2907143 TI - Concomitant release of sialic acids and calcium by neuraminidase from rat aorta in situ. AB - Male Wistar rats were heparinized and killed with pentobarbital. The upper and lower ends of the aortae were cannulated and the blood was washed out with saline until the washings contained calcium and sialic-acid-reacting material at minimal concentrations. The aortae were perfused with neuraminidase for 15 min. This caused the appearance of calcium as well as of sialic acids in the perfusate in total amounts of about 5.3 nmol and about 3.6 nmol per aorta respectively. The molar ratio of about 1.5 is sufficiently close to that determined for the association of calcium with sialic acids in vitro to suggest that their association is similar in vivo. PMID- 2907144 TI - A structural approach to pathological crystallizations. Gout: the possible role of albumin in sodium urate crystallization. AB - The interactions between sodium urate monohydrate (MSU) crystals and human serum albumin (HSA) were investigated in vitro in relation to the disease of gout. It was found that HSA accelerates (by up to ten times or even more) the nucleation of MSU crystals at a pH of more than 7.5, but only to a much lesser extent (1.2 times) at pH 7.0. Protein denaturation, as well as blocking exposed carboxylate groups on the protein, substantially reduced the nucleating effect. By use of immunofluorescence, immunogold labelling and crystal morphology studies, albumin was shown to interact preferentially with the (110) faces of MSU crystals. Taking these results into consideration, a mechanism is proposed whereby albumin stabilizes MSU crystal nuclei by interaction of structured carboxylate-containing protein domains with planes of the incipient crystal exposing sodium cation layers. PMID- 2907146 TI - [The biochemical basis of pharmaceutical chemistry. 4. Modification of central neurobiochemical processes by drugs]. PMID- 2907145 TI - The role of purines in the maintenance of meiotic arrest in mammalian oocytes. PMID- 2907147 TI - Action of clonazepam and clorazepate on cortical self-sustained after-discharges in the rat. AB - Self-sustained after-discharges (SSADs) induced by electric stimulation of the sensorimotor cortex in rats exhibited under control conditions a significant progressive prolongation with repeated stimulations. Clonazepam not only blocked this increase in duration but it suppressed and/or abolished SSADs in a dose dependent manner. Clorazepate in the lowest dose used (10 mg/kg) did not change SSADs. The two higher doses (25 and 50 mg/kg) blocked the prolongation of the 4th SSAD, i.e. this effect had a relatively long latency. PMID- 2907148 TI - Genetic factors as determinants of infectious disease transmission in human communities. AB - Genetic factors may play an important role in individual susceptibility to infection. Hitherto this problem has been investigated by attempting to relate the distribution of genetic polymorphisms in populations to present or past infection, or by analysing specific infections by classical twin studies or group comparisons. There is reasonable evidence that the common red-cell polymorphisms involving haemoglobin, enzymes or membrane have been maintained by relative resistance to malaria. Blood-group heterogeneity, including secretor status, may reflect varying susceptibility to bacterial, virus and yeast infection. There is increasing evidence that the HLA-DR system may be involved in modifying the clinical course of bacterial, virus and parasitic infection. So far no specific resistance or susceptibility loci similar to those found in murine models have been found in man. DNA analysis, particularly involving restriction fragment length polymorphism associations with candidate genes, offers a valuable new approach to this problem. PMID- 2907149 TI - Implications of genetics for the epidemiology and control of leprosy. AB - This paper reviews the rationale and history of genetic studies related to leprosy, and considers their implications for the epidemiology and control of the disease. A long tradition of genetic studies in leprosy was initiated by early impressions that the disease clusters within families. Investigations were first motivated by an attempt to understand population patterns, and the focus shifted from investigations of racial differences to investigations of families, of twins and ultimately of genetic markers. The strongest evidence for genetic influence has come from studies of HLA segregation patterns within families, and this has led to elegant in vitro work demonstrating the role of HLA-DR alleles in mediating T-cell reactions in conjunction with antigens of Mycobacterium leprae. The epidemiological implications of this work are not yet clear. The emphasis on family-segregation studies may have given a biased impression because of their requirement for multi-case families. There is evidence that the genetic mechanisms underlying leprosy differ within and between populations. One possible application of the current work would be the use of HLA-DR-specific reactions to identify epitopes of M. leprae which should be excluded from future vaccine preparations. PMID- 2907150 TI - Ecological interactions in the transmission of the leishmaniases. AB - Epidemiological studies on the leishmaniases are disclosing a multiplicity of Leishmania species infecting a wide range of wild mammalian hosts, from marsupials to monkeys. In the primitive, silvatic habitat these parasites are transmitted by an equally wide variety of phlebotomine sandfly species (Diptera: Psychodidae: Phlebotominae). Transmission is not haphazard, however, and available evidence points to the existence of environmental barriers that normally limit the different Leishmania species to specific sandfly vectors, transmitting to certain mammalian species, within distinct ecotopes. In this situation, humans may become infected by a variety of leishmanial parasites when intruding into the different enzootics, if the sandfly vectors are anthropophilic. Many are not, however, and their parasites rarely, if ever, make contact with the human host. Natural or man-made ecological changes may result in modification of the epidemiological pattern of leishmaniasis, leading to either a reduction or an increase in the human disease. PMID- 2907151 TI - Population ecology of intestinal helminth infections in human communities. AB - The distribution of worm burdens in human populations is a major determinant of both the dynamics of transmission and the level of community morbidity. The distribution exhibits convexity with host age, which appears to correlate with exposure in the young age-classes but not in adults, and may be evidence for the development of an acquired immune response. The distribution between individuals is typically overdispersed. Individuals are predisposed to high (or low) intensity of infection and to a correspondingly high (or low) rate of acquisition of infection. A major epidemiological question is whether this reflects individual differences in environmental exposure or susceptibility. Environmental studies that have observed clustering of intense infection in particular households are supportive of either mechanism. Individual host behaviours that predispose to infection have an overdispersed distribution and may alone, or as compounding factors, generate the observed distribution of infection intensity. Factors such as host nutrition and physiology may modify host immune responsiveness and hence susceptibility. Preliminary evidence suggests correlates between infection intensity and HLA class II antigens, and tentatively implies a genetic factor in susceptibility. These findings suggest that further understanding of the relative importance of environmental factors and resistance to the acquisition of intense infection is dependent upon a multidisciplinary approach to epidemiological field study. PMID- 2907152 TI - Molecular variation in vector-borne plant viruses: epidemiological significance. AB - Patterns of variation are examined in four groups of plant viruses, with special reference to their particle proteins and to changes in vector transmissibility and specificity. In the nepoviruses and potyviruses, non-circulative transmission, by nematodes and aphids respectively, seems dependent on structural features on the surface of the virus particles. The N-terminal part of the particle protein may play the key role in potyviruses. Similarly in the luteoviruses, and possibly in the geminiviruses, specificity of circulative transmission by aphids, whiteflies and leafhoppers is linked to the antigenic specificity of the virus particles. Among naturally occurring isolates of the same virus, variation seems often to be discontinuous, and is predominantly of two sorts. Minor variations, characterized by loss of an epitope or substitutions of a few amino acids, can be associated with loss of transmissibility in luteoviruses and potyviruses, or have no effect. Major variations are associated with differences in vector specificity and seem likely to involve radical genetic changes that have evolved over long periods. The adaptation of virus particle proteins for transmission by vectors probably results in conservation of the genes that encode them, and in greater conservation of some parts of these genes than of others. PMID- 2907153 TI - Molecular and biochemical studies of the evolution, infection and transmission of insect bunyaviruses. AB - Members of the Bunyaviridae family of RNA viruses (bunyaviruses, hantaviruses, nairoviruses, phleboviruses and uukuviruses) have been studied at the molecular and genetic level to understand the basis of their evolution and infection in vertebrate and invertebrate (arthropod) hosts. With the exception of the hantaviruses, these viruses infect and are transmitted by a variety of blood sucking arthropods (mosquitoes, phlebotomines, gnats, ticks, etc.). The viruses are responsible for infection of various vertebrate species, occasionally causing human disease, morbidity and mortality (e.g. Rift Valley fever, Crimean-Congo haemorrhagic fever, Korean haemorrhagic fever). Genetic and molecular analyses of bunyaviruses have established the coding assignments of the three viral RNA species and documented which viral gene products determine host range and virulence. Ecological studies, with molecular techniques, have provided evidence for bunyavirus evolution in nature through genetic drift (involving the accumulation of point mutations) and shift (RNA-segment reassortment). PMID- 2907154 TI - New approaches to the serotypic analysis of the epidemiology of Plasmodium falciparum. AB - Considerable antigenic heterogeneity of Plasmodium falciparum has been demonstrated in natural parasite populations. However, very little is known about the relative virulence, transmission efficiency and prevalence over space and time of parasites expressing different serotypes of variant antigens. The recent application of recombinant DNA techniques to express a wide range of P. falciparum antigens in Escherichia coli has led to a better understanding of the molecular basis of antigenic diversity of a number of parasite proteins including the precursor to the major merozoite surface antigen (PMMSA) and the heat-stable S-antigens. Highly specific reagents such as DNA probes, monoclonal antibodies and polyclonal antisera to either cloned antigens or synthetic peptides have become available for serotypic analysis of natural parasite populations. With these reagents important epidemiological questions can now be asked concerning the population biology of different serotypes of P. falciparum. The use of the polymorphic S-antigen system as a serotypic marker to analyse the transmission dynamics of P. falciparum in Madang, Papua New Guinea (PNG) is discussed. Results of serotyping studies with the S-antigen system highlight the complexities of malaria transmission, which require consideration in the design of malaria vaccine trials. PMID- 2907155 TI - Longitudinal studies on human schistosomiasis. AB - A major difficulty in understanding the epidemiology of human schistosomiasis has been to distinguish between acquired immunity and reduced exposure as possible reasons for an observed decline, in older individuals, of levels of superinfection or of reinfection after chemotherapy. A series of studies of Schistosoma mansoni infections in Kenya has been undertaken to approach this problem, by investigation of intensities of reinfection after treatment of individuals whose levels of contact with contaminated water is subsequently observed. Intensities of reinfection are highest among younger children, thereafter declining sharply. This decline can be attributed only in part to age related changes in the duration and nature of exposure; there is also evidence for the development of an acquired resistance to reinfection that is dependent both on age and on previous experience of infection, and that may be immunologically mediated. Evidence has been obtained that the slow development of this acquired immunity with age may be associated with the early development and subsequent slow decline of inappropriate immune responses that 'block' the effect of potentially protective responses. Implications of these findings for immunological intervention through vaccination are discussed. PMID- 2907156 TI - The dynamics of vector-transmitted diseases in human communities. AB - The development of vector-transmitted disease models and their application to field studies is reviewed. The key concepts of the basic rate of reproduction and disease transmission threshold are explained, and their application to disease control briefly illustrated. The complications involved in producing appropriate models are discussed for the case of the trypanosomatid parasites Leishmania and Trypanosoma that frequently have more than one vertebrate host and are often fatal in the human host. A two-species, vector-borne disease model allows a quantification of the role of animal reservoirs in maintaining human diseases. Human prevalence may be determined more by the parasitological characteristics of wild reservoir species, about which little is generally known, than by any other single feature of the complex interaction between parasites, vectors and hosts. Domestic animals are often ideal reservoirs, maintaining large numbers of vectors and considerably enlarging the parasite pool. When vector-transmitted diseases are fatal to the human host, human and vector dynamics interact in ways which may cause epidemic cycles, low-level endemic equilibria or disease extinction. For both leishmaniasis and trypanosomiasis it is suggested that a very small number of chronic human cases can maintain the disease in the human population over long periods of time between epidemic outbreaks. They may also be important in the maintenance of geographically distinct foci, characteristic of human trypanosomiasis in Africa. Finally there is a plea to establish a tradition of field observation leading to, and being directed by, mathematical models which in turn are modified as the observations accumulate. All too often, one-way traffic between the two results in slow, or misguided, progress. PMID- 2907157 TI - Gastrointestinal nematode parasites and the stability and productivity of intensive ruminant grazing systems. AB - This paper uses mathematical models, describing the transmission dynamics of directly transmitted gastrointestinal nematode parasites of sheep and cattle, to examine the impact of these parasites on the stability and productivity of ruminant grazing systems. Current models of the ecology of grass growth under grazing, and the epidemiology of trichostrongylid nematode parasites of ruminants, are combined in a formulation that captures the general features of the plant - (ruminant) herbivore - parasite interaction. The simplest case, in which herbivore numbers are constant and not food limited (the norm for many agricultural systems) is considered in detail. The effect of gastrointestinal parasitism in reducing herbivore feeding rates is shown to act as a potential density-dependent constraint on the parasite's infection rate. The process is manifested in the model as a progressive linearization of the relation between herbivore feeding rate and plant density at the parasite equilibrium. This effect acts to stabilize the dynamics of the model grazing system and significantly affects its predictions about the impact of parasite control and the pattern of host productivity. Model predictions are discussed in the light of relevant field observations, and areas for future research are identified. PMID- 2907158 TI - The transmission dynamics of human immunodeficiency virus (HIV). AB - The paper first reviews data on HIV infections and AIDS disease among homosexual men, heterosexuals, intravenous (IV) drug abusers and children born to infected mothers, in both developed and developing countries. We survey such information as is currently available about the distribution of incubation times that elapse between HIV infection and the appearance of AIDS, about the fraction of those infected with HIV who eventually go on to develop AIDS, about time-dependent patterns of infectiousness and about distributions of rates of acquiring new sexual or needle-sharing partners. With this information, models for the transmission dynamics of HIV are developed, beginning with deliberately oversimplified models and progressing--on the basis of the understanding thus gained--to more complex ones. Where possible, estimates of the model's parameters are derived from the epidemiological data, and predictions are compared with observed trends. We also combine these epidemiological models with demographic considerations to assess the effects that heterosexually-transmitted HIV/AIDS may eventually have on rates of population growth, on age profiles and on associated economic and social indicators, in African and other countries. The degree to which sexual or other habits must change to bring the 'basic reproductive rate', R0, of HIV infections below unity is discussed. We conclude by outlining some research needs, both in the refinement and development of models and in the collection of epidemiological data. PMID- 2907159 TI - Augmentation of isoproterenol-induced drinking by acute treatment with certain dopaminergic agonists. AB - Bromocriptine (1 mg/kg, IP), a dopaminergic agonist that crosses the blood-brain barrier, augmented the dipsogenic responsiveness of rats to acute administration of the beta-adrenergic agonist, isoproterenol (15 micrograms/kg, SC), when administered at the same time. When administered alone, it had no effect on either water intake or urine output. Dopamine (20 mg/kg IP), which does not cross the blood-brain barrier, also augmented the dipsogenic responsiveness to acute administration of isoproterenol. However, a major difference between the responses to bromocriptine and dopamine was that the latter augmented drinking only when administered 15 to 30 min prior to isoproterenol. During the 30 min between injection of dopamine and the injection of isoproterenol, output of urine and sodium increased approximately 6-fold above the level of controls such that the concentration of the urine excreted by the treated group was approximately isotonic. However, in spite of a 6-fold increase in output of urine by the treated, compared to the control group, dopamine-treated rats ingested water only to the same extent as untreated controls when access to water was allowed. This suggests that an isotonic contraction of extracellular fluid may not induce a dipsogenesis. It also suggests that the augmentation of isoproterenol-induced drinking by dopamine was not the result of a dehydration-induced drink superimposed on the isoproterenol-induced drink. The centrally and peripherally acting dopaminergic antagonist, spiroperidol (spiperone), inhibited the isoproterenol-induced drinking response in a dose-related fashion. However, the peripherally acting dopaminergic antagonist, domperidone,was without effect on isoproterenol induced drinking.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2907160 TI - Monoamine metabolism and its responses to food deprivation in the brain of Zucker rats. AB - Monoamines and their metabolites levels were simultaneously measured by high performance liquid chromatography in brain regions of lean and fatty Zucker rats when fed ad lib and deprived of food for 72 hr to evaluate each monoamine metabolism. Metabolite/monoamine ratios were shown for brevity to represent its metabolism. 3-Methoxy-4-hydroxyphenylethyleneglycol/noradrenaline ratios were not affected by the phenotype factor but increased in the cortex of fatty rats and reduced in the midbrain of both phenotypes after fasting; the interaction between phenotype and feeding factors was observed in the cortex and hippocampus. 3,4 Dihydroxyphenylacetic acid/dopamine ratios were increased in the cortex of deprived fatty rats and in the medulla-pons of ad lib-fed fatties compared with lean counterparts and also increased in the striatum of lean rats after food deprivation; the interaction was observed in the cortex, midbrain and medulla pons. Homovanillic acid/dopamine ratios were decreased in the striatum of deprived fatty rats and in the midbrain and medulla-pons of fatty rats whether deprived or not, but the ratios were not significantly changed by fasting; the interaction was observed in the striatum. 5-Hydroxyindoleacetic acid/5 hydroxytryptamine ratios were reduced in the cortex, striatum and medulla-pons of fatty rats in both feeding states and in the midbrain of deprived fatties, and after food deprivation increased in the cortex and midbrain of lean rats and in the hippocampus of both phenotypes; the interaction was observed in the midbrain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2907161 TI - D-1 and D-2 receptor antagonists decrease corn oil sham feeding in rats. AB - Intraperitoneal injection of the highly selective D-1 and D-2 receptor antagonists, SCH 23390 and (-)-raclopride, respectively, produced a dose-related decrease in the intake of corn oil in a 30-min, sham-feeding test. The threshold dose for a significant decrease in intake was 100 micrograms.kg-1 for SCH 23390 and 200 micrograms.kg-1 for raclopride. These doses did not impair rats' latencies to initiate sham feeding, and they did not produce any overt motor deficits. These data, therefore, are consistent with the hypothesis that central dopaminergic activity at both D-1 and D-2 receptors is necessary for the normal processing of the sensory and/or hedonic effects of the oral stimuli produced by corn oil during sham feeding. PMID- 2907162 TI - Monoamine transmitter activity in lateral hypothalamus during its perfusion with insulin or 2-DG in sated and fasted rat. AB - A unique profile of neurochemical events is proposed to occur in the diencephalon which is contingent upon the nutrient status of the animal. In this first of a series of investigations, we selected the lateral hypothalamus (LH) in order to determine its specific resting profile of monoaminergic neurotransmitters and their principal metabolites. The neuronal pattern of activity was studied during sated and fasted conditions as well as during a local glucoprivic challenge to the LH. After permanent guide cannulae for push-pull perfusion were implanted in female Sprague-Dawley rats, the LH was perfused repeatedly with an artificial CSF, at a rate of 20 microliters/min, in order to collect a series of 5.0 min samples. Aliquots of each perfusate were assayed directly using a high performance liquid chromatography system with electrochemical detection (HPLC-EC) for pg/microliter concentrations of norepinephrine (NE), dopamine (DA) and serotonin (5-HT). In comparison to the basal levels of amines during the sated condition, when the rat was food-deprived for 20-22 hr, the release of NE, DA, and 5-HT was significantly lower than that observed under the sated condition. Further, the turnover of NE in the LH was concurrently attenuated as reflected by the lower levels of MHPG in the perfusate, thus demonstrating the modification in catecholamine activity produced in the LH by the condition of hunger. When either 10 micrograms/microliters 2-deoxy-D-glucose (2-DG) or 4.0 mU/microliter insulin was incorporated into the CSF perfused in the LH, the efflux of DA was significantly enhanced independent of the state of satiation. In addition, the proportion of both NE and DA to 5-HT was likewise increased by either of these centrally acting substances, while the turnover of 5-HT was enhanced and NE and DA turnovers were reduced. Perfusion of 2-DG in the LH of the fasted rat caused a significant reduction in catecholamine turnover in terms of MHPG/NE, VMA/NE, DOPAC/DA and HVA/DA ratios. Moreover, 2-DG increased NE/5-HT while lowering the NE/DA ratio, and enhanced simultaneously the 5-HTOL/5-HT ratio. In the sated rat, 2-DG attenuated the release of 5-HT from the animal's LH, whereas insulin caused a shift in the proportions of NE/5-HT and DA/5-HT. Further, the peptide served to reduced the efflux of 5-HT, enhanced the turnover of 5-HT while diminishing DA turnover, and shifted the metabolism of NE from MHPG to VMA.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2907163 TI - Growth hormone responses to the alpha 2-adrenoceptor agonist guanfacine and to growth hormone releasing hormone in depressed patients and controls. AB - Growth hormone (GH) responses to the alpha 2-adrenoceptor agonist guanfacine and to GH releasing hormone (GHRH) were measured in 13 patients fulfilling Research Diagnostic Criteria and DSM-III criteria for major depressive disorder and in 13 controls matched for age and sex. Dexamethasone suppression tests were performed in all subjects. The peak GH response to guanfacine correlated to the peak GH response to GHRH both in depressed patients and in controls. Neither the response to guanfacine nor the response to GHRH was significantly lower in depressed patients than in controls. Dexamethasone suppression tests, which were performed about 3 days before the GH stimulation tests, were abnormal in 61% (8/13) of the depressed patients but in none of the controls. No difference between dexamethasone suppressors and nonsuppressors with respect to GH response to guanfacine or GHRH was observed. The data are discussed in relation to the blunted GH response to clonidine described in depression. PMID- 2907164 TI - Relationship of increased food intake and plasma ACTH levels to 5-HT1A receptor activation in rats. AB - Various putative agonists of the 5-HT1A receptor subtype induce feeding in rats, probably by activating raphe somatodendritic 5-HT autoreceptors. These drugs also produce a marked increase in plasma concentrations of corticotropin (ACTH). In the present experiment we attempted to localize the site of action of 5-HT1A agonists on the secretion of ACTH and examined the relationship between 5-HT1A agonist-induced feeding and ACTH secretion. Rats were injected with either the high affinity 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) (0.016-1.0 mg/kg, s.c.) or the novel anxiolytics buspirone, gepirone or ipsapirone (2.0-16.0 mg/kg, s.c.), and either had their food intake measured 2 hr post injection or were sacrificed 30-40 min post injection for measurement of plasma ACTH. Plasma ACTH also was measured in rats pretreated with the serotonin synthesis inhibitor, para-chlorophenylalanine (PCPA) for three days (150 mg/kg, i.p. per day) and subsequently injected with 8-OH-DPAT (0.3 mg/kg, s.c.). As previously reported, the 5-HT1A agonists increased both food agonists increased both food intake and plasma ACTH concentrations. After 8-OH-DPAT, ipsapirone and gepirone the amount of food consumed was positively correlated with the concentration of plasma ACTH. No such correlation was evident following buspirone. PCPA pretreatment resulted in near total depletion of brain 5-HT content but had no effect on the ACTH rise induced by 8-OH-DPAT. Therefore, in contrast to the presynaptic site previously proposed for 5-HT1A agonist-induced feeding, the present results suggest a agonist-induced feeding, the present results suggest a postsynaptic location for the 5-HT1A receptor mediating ACTH release. PMID- 2907165 TI - The promise of receptor studies in psychophysiologic research. AB - Most research on reactivity to stressors limits its focus to the neurohormonal and cardiovascular components of reactivity. There is, however, another area of investigation with important implications to this field. Receptor binding techniques provide a direct measure of the functional link between neurohormonal signals and the responses they stimulate. Receptor measurement would enable psychophysiologic studies to begin to address the complete triad of signal emission/reception/end-organ response that underlies all reactivity patterns. This paper reviews adrenergic receptor physiology, methods, and research pertinent to reactivity. Our intention is to encourage greater consideration of these important issues in reactivity research. PMID- 2907166 TI - Control of release of vasopressin by neuroendocrine reflexes. AB - The neurones in the supraoptic and paraventricular nuclei (SON and PVN) which secrete vasopressin are separate from those which secrete oxytocin and are distributed in different parts of the nuclei. They may be distinguished electrophysiologically by a characteristic phasic pattern of firing. A selective afferent neural input to these neurones would provide a mechanism for the release of vasopressin independently of oxytocin in response to appropriate physiological stimuli. Release of vasopressin is controlled by changes in blood volume or pressure ('volume control') and in plasma osmolality ('osmotic control'). Stimuli involved in volume control such as haemorrhage, hypotension and carotid occlusion cause vasopressin to be released into the circulation with little or no detectable oxytocin. An osmotic stimulus releases vasopressin alone in some species but not apparently in the rat in which both hormones are released. Volume control is mediated reflexly by peripheral receptors in the cardiovascular system. Activation of baro- and stretch receptors results in inhibition, and activation of chemoreceptors in stimulation, of release. Afferent impulses from these receptors are conveyed in the vagi and carotid sinus nerves to the NTS on the dorsal surface of the brain stem. All afferent impulses to the NTS are excitatory. It follows that the afferents from chemoreceptors must stimulate an excitatory, and those from baro- and stretch receptors an inhibitory, projection from the NTS to the vasopressin-secreting cells in the SON and PVN. Two alternative models are presented of the neural pathways and transmitters involved. The model of Fig. 2 shows an excitatory relay through a cholinoceptive area on the ventral surface of the brain stem which has been termed the 'nicotine sensitive area' because topical application of nicotine to this area in the cat released vasopressin without oxytocin. An inhibitory relay is shown through the A1 group of noradrenergic neurones on the ventral surface which selectively innervate the vasopressin-secreting neurones in the SON. This model implies an inhibitory role for noradrenaline acting on beta- or alpha 2-receptors. However the most recent investigations suggest an excitatory, rather than inhibitory, function of the A1 noradrenergic neurones involving alpha 1-receptors. This is the basis of the model in Fig. 3. The A1 neurones project either directly to the SON and PVN or indirectly through the lateral preoptic nucleus which lies in close proximity to the SON. The nicotine-sensitive area may be coincident with the A1 group of noradrenergic neurones.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2907167 TI - The effects of somatostatin on the arachidonate cascade of platelets. AB - Somatostatin (10(-9) M) significantly elevated the synthesis of thromboxane B2 in rat platelets. The transformation of arachidonic acid to active lipoxygenase metabolites was suppressed by somatostatin (10(-9) and 10(-8) M). The ratio of the lipoxygenase/cyclooxygenase products was significantly reduced by the polypeptide (10(-9) and 10(-8) M) in rat platelets. Higher concentrations (10( 7), 10(-6) and 10(-5) M) of somatostatin did not modify the lipoxygenase pathway of the platelets. The synthesis of the vasoconstrictor - proaggregatory cyclooxygenase products was stimulated by the polypeptide (10(-9) and 10(-8) M), while the formation of vasodilatator - antiaggregatory cyclooxygenase metabolites was induced by higher concentrations of somatostatin (10(-7) and 10(-6) M). Somatostatin might act on the deacylation process of phospholipids, reducing the free arachidonic acid substrate level, resulting in a lower lipoxygenation rate in the platelets, which could be responsible for the increased formation of thromboxane. The contradictory results reported by others concerning the action of somatostatin on the platelet function might be explained by our results that the effect of somatostatin depends on the applied dose. PMID- 2907168 TI - Approaches to the treatment of lithium-resistant mania. PMID- 2907169 TI - Regulatory mechanisms in the luminal and portal release of vasoactive intestinal polypeptide during vagal nerve stimulation in the cat. AB - The effect of vagal stimulation in chloralose-anesthetized cats on release of vasoactive intestinal polypeptide into the jejunal lumen and portal venous blood was tested simultaneously, and the effect of atropine and hexamethonium was investigated to elucidate the regulatory mechanisms involved in the release. Vagal stimulation caused a significant increase in vasoactive intestinal polypeptide concentrations in the luminal perfusates. A significant concomitant increase was seen in portal plasma. Gel filtration chromatography of luminal and portal samples demonstrated that the vasoactive intestinal polypeptide coeluted with synthetic porcine vasoactive intestinal polypeptide. Vasoactive intestinal polypeptide infusion at 80 and 160 pmol/kg.min produced portal plasma levels of at least 3000 pM but did not increase vasoactive intestinal polypeptide concentrations in the luminal perfusates. Thus, luminal vasoactive intestinal polypeptide originates from gastrointestinal tissue rather than by transduction from the circulation. Vagally induced release of vasoactive intestinal polypeptide into the lumen and portal plasma was not abolished by atropine but was totally suppressed by hexamethonium. The regulatory mechanisms controlling the parallel release of vasoactive intestinal polypeptide into both the jejunal lumen and portal circulation are identical and involve a non-muscarinic process which is under cholinoceptive, nicotinic control. PMID- 2907170 TI - Variations of plasma immunoreactive motilin, pancreatic polypeptide, gastrin and somatostatin along the duodenal motility cycle in the pig. AB - The peripheral plasma concentrations of immunoreactive motilin, pancreatic polypeptide (PP), somatostatin and gastrin were measured in 7 pigs fasted to 24 h and subsequently fed a standard meal. Plasma motilin peaked during the last part of phase II activity of the migrating myoelectric complex (MMC) sequence (25.2 +/ 2.3 pM), the lowest value being recorded during phase I (10.6 +/- 1.5 pM) after a 24 h fast. Plasma motilin remained at a low level during the digestive pattern of duodenal activity, no fluctuation occurring when the first postprandial MMC recurred. At variance analysis, gastrin and PP were not released phasically with MMC in the fasting state, while at autocovariance both peptides tended to fluctuate during the MMC sequence with positive and negative peaks at regular intervals along MMC cycles. No variation of plasma somatostatin was observed in the fasting animals. These findings argue against a major role of circulating PP, gastrin and somatostatin-like components in the control of fasted and post absorptive duodenal motility in pigs while the role of motilin remains equivocal. PMID- 2907171 TI - Insulin and glucagon secretion in rats: effects of calcitonin gene-related peptide. AB - Immunoreactive calcitonin gene-related peptide (CGRP) has been shown to occur in intrapancreatic nerves and islet somatostatin cells in the rat. Therefore, we investigated the effects of CGRP on insulin and glucagon secretion in the rat. CGRP was infused i.v. at one of 3 dose levels (4.3, 17 or 68 pmol/min). Infusion of CGRP alone was found to elevate basal plasma levels of both insulin and glucagon. In contrast, CGRP impaired the plasma insulin responses to both glucose (7 mg/min; P less than 0.001) and arginine (8.5 mg/min; P less than 0.001), and inhibited the arginine-induced increase in plasma glucagon concentrations (P less than 0.001). Since CGRP and somatostatin are colocalized within the D-cells, we also infused CGRP and somatostatin together at equimolar dose levels (17 pmol/min), with glucose (7 mg/min). By that, the increase in plasma insulin concentrations decreased more rapidly than during infusion of either peptide alone. Since alpha 2-adrenoceptor activation is known to inhibit glucose stimulated insulin secretion, we also infused CGRP together with the specific alpha 2-adrenoceptor antagonist yohimbine (37 nmol/min). In that way, the plasma insulin-lowering effect of CGRP was prevented. We have shown in the rat: (1) that CGRP stimulates basal insulin and glucagon secretion; (2) that CGRP inhibits stimulated insulin and glucagon secretion; (3) that CGRP and somatostatin more rapidly induce a potent inhibitory action on glucose-stimulated insulin secretion when given together; and (4) that the alpha 2-adrenoceptor antagonist, yohimbine, counteracts the inhibitory action of CGRP on glucose-stimulated insulin secretion. We suggest that CGRP is of importance for the regulation of insulin and glucagon secretion in the rat. The mechanisms behind the islet effects of CGRP can not be established by the present results, though they apparently require intact alpha 2-adrenoceptors. PMID- 2907172 TI - Gastrin and somatostatin in the rat antrum. The effect of removal of acid secreting mucosa. AB - Female rats were subjected to operations aimed at reducing the amount of oxyntic gland mucosa draining its acid secretion to the antrum. The rats were provided either with Heidenhain or Pavlov pouches reducing the oxyntic mucosa draining its secretion to the antrum by about 50% or subjected to various degrees (75, 90 and 100%) of fundectomy. Ten weeks following surgery, plasma levels of gastrin and somatostatin were assayed. At the same time, antral mucosal content of gastrin and somatostatin was determined as well as the mucosal density of these hormone producing cells. There was a relationship between the amount of acid-secreting mucosa removed and the ensuring plasma concentration of gastrin. Thus, a stepwise increase in plasma gastrin was found with the highest levels obtained in rats subjected to 90 or 100% fundectomy. The somatostatin concentration in plasma was reduced only in rats subjected to fundectomy with the most sustained decrease in animals in which all oxyntic gland mucosa had been removed. There was also a relationship between the amount of acid-secreting mucosa removed and the gastrin content of the antral mucosa. An inverse relationship seemed to exist between antral gastrin and somatostatin concentrations. However, a significant decrease in somatostatin concentration of the antral mucosa was seen only in rats subjected to a fundectomy. The number of gastrin cells in the antral mucosa was increased in fundectomized rats only, with the largest density seen in rats deprived of all oxyntic mucosa. A corresponding decrease in the number of somatostatin cells was noticed. Our results would suggest an apparent functional relationship between antral gastrin and somatostatin cells, where the antral acid load (or pH) appears to be the major factor of physiological significance. PMID- 2907173 TI - Reduced somatostatin-28-(1-12)-like immunoreactivity in cerebral cortex of dogs with an Eck fistula and somatostatin molecular forms in brain. AB - Somatostatin-28-(1-12)-like immunoreactivity (S28(1-12)LI) in brains of Eck fistula dogs, prepared as an experimental model of hepatic encephalopathy, was measured. Significant reductions of S28(1-12)LI were observed in all cortical regions of Eck fistula dogs. The reductions of S28(1-12)LI were significantly correlated with decreases in somatostatin-14-like immunoreactivity (S14LI) in the cortical region. The ratios of S28(1-12)LI to S14LI in all cortical regions were not different between Eck fistula and normal dogs. Additionally, no difference in gel chromatographic profiles of S28(1-12)LI and S14LI was observed between Eck fistula and normal dogs. These results imply that reduced somatostatin immunoreactivity in hepatic encephalopathy may be caused not by altered degradation but by reduced production of prosomatostatin. Our S28(1-12)LI assay system could detect prosomatostatin(1-76) and S28(1-12) and the S14LI system prosomatostatin, S28 and S14. S28(1-12)LI/S14LI ratios in cortex were 0.64-0.83 and these were significantly different from those (1.02-1.36) in thalamus, midbrain and medulla. Relative proportions of prosomatostatin (20%) and S28 (23 24%) in cortex were larger than those (6-7% and 5-7%, respectively) in thalamus, midbrain and medulla. The differential distribution of these molecular forms suggests that processing of prosomatostatin in cortex may be different from that in thalamus, midbrain and medulla. PMID- 2907174 TI - Characterization of somatostatin binding sites in isolated rat adipocytes. AB - Somatostatin binding sites were characterized in isolated rat adipocytes. The binding was found to be saturable, reversible, and time- and temperature dependent. The somatostatin binding sites are principally located on the cell surface. 125I-[Tyr11]somatostatin binding was not inhibited by glucagon and angiotensin II. By contrast, native somatostatin and somatostatin-28 displaced labeled peptide with a similar ED50: 50 nM. Scatchard analysis pointed to the existence of two classes of binding sites, with a Kd of 7.64 nM for the high affinity sites and a Kd of 295 nM for the low-affinity ones. Comparison of somatostatin receptor binding and its lipolytic action in isolated rat adipocytes suggested that the spare receptor phenomenon cannot be applied to the lipolytic action of somatostatin in rat adipose tissue. PMID- 2907175 TI - [Covering losses of cutaneous substance of the leg and foot using skin flaps. Apropos of 76 cases]. AB - Between 1983 and 1987, 76 flap grafts were performed in the leg and foot. In general, 3 types of flap were used: --51 ipsilateral flaps, the majority of which were musculo-cutaneous flaps from the medial head of gastrocnemius (17 cases). - 17 cross-leg flaps from the opposite limb, the majority of which were medial fascio-cutaneous flaps (13 cases). --8 free flaps, making use of microsurgical techniques. The indications for cross-leg flaps and free flaps have become more limited in favour of local regional pedicle flaps. The lower part of the leg and amputation stumps in the foot are easily covered by distal leg pedicle flaps and amputation stumps of the upper third of the leg can be covered by a flap of fascia lata with a distal pedicle based on the superolateral branches of the peri articular plexus of the knee. PMID- 2907177 TI - [Specific receptors for atrial natriuretic polypeptide and cyclic GMP production by particulate guanylate cyclase in human lung]. PMID- 2907176 TI - [Type IIa multiple endocrine neoplasia with asymptomatic pheochromocytoma]. PMID- 2907178 TI - [Betaxolol versus nifedipine in the treatment of essential hypertension]. PMID- 2907179 TI - [Algodystrophy with scintigraphic hypofixation recurring in the same bone segment]. PMID- 2907180 TI - Studies of serum lipids in hypercholesterolaemic rabbits treated with doxazosin. AB - Serum lipids were studied in hypercholesterolaemic rabbits treated with the selective alpha 1-adrenoreceptor antagonist doxazosin. Hypercholesterolaemia had been induced by cholesterol feeding which raised mean (+/- SEM) total serum cholesterol from 1.4 (+/- 0.1) mmol/l to 84.1 (+/- 3.6) mmol/l. A cross-over design was used to compare the effect of doxazosin with placebo in 20 rabbits of which 16 completed the study. Doxazosin (2 mg/kg) or placebo vehicle was administered subcutaneously once daily for three weeks. Compared with placebo, doxazosin produced an 8.6% greater reduction in total serum cholesterol. This difference did not, however, reach statistical significance. PMID- 2907181 TI - Serum bilirubin subfractions in patients with alcohol abuse during detoxication. AB - Sera were obtained from 41 alcohol abusers consecutively admitted for detoxication. Blood samples were withdrawn on the second, fourth and seventh days of abstention. Initial bilirubin values were moderately elevated in 10 patients. Determination of the bilirubin subfractions by high performance liquid chromatography showed elevated values of unconjugated (alpha), monoconjugated (beta), diconjugated (gamma) and albumin-bound (delta) bilirubin, in 8, 15, 4 and 15 patients, respectively. During abstention, the total bilirubin value normalized rapidly, only three patients still had values above the upper reference limit after 7 days. In patients with initially elevated values of bilirubin subfractions, only a few had elevated beta and gamma levels on the seventh day, whereas delta levels decreased at a slower rate and remained virtually unchanged. On admission, 27 patients exhibited elevated levels of serum bile acids; these values decreased during abstention and after 7 days only six patients had slightly elevated values. Only five patients had initially elevated levels of alkaline phosphatase (ALP). These became normalized in all but two patients during abstention. The results suggest that mild cholestasis is common among alcohol-abusers without clinically evident liver disease and that these changes are reversible on abstention. PMID- 2907182 TI - Ultrasound in the evaluation of retractile and truly undescended testes. AB - The aim of this study was to evaluate ultrasound and clinical examination in the assessment of the exact position of an undescended testicle, and to see whether ultrasound could help discern retractile and truly undescended testicles. One hundred and twenty-three undescended testicles were examined. Of 113 detectable testicles 47 were assessed retractile and 66 truly undescended of which 60 were operated. Ultrasound had a sensitivity, specificity and accuracy of 100% for testicles positioned distally to the internal ring. The results of clinical examination by a urologist was poor, especially for testicles located in the inguinal canal. Bilateral symptoms were most common in the retractile group. Retractile testicles dominated at the age group 6-8 years and were most commonly found in the intermediate and external ring positions. Truly undescended testicles preferred the inguinal canal and a subcutaneous everted position. Differences are statistically significant. A discrimination analysis between retractility and true maldescent was performed based on whether symptoms were uni or bilateral, patient's age and the position of the testicle. The most dominant factor was whether symptoms were uni- or bilateral. PMID- 2907183 TI - Benevolent bradykinins. PMID- 2907184 TI - The prevalence of depot neuroleptic treatment among West Indians and Asians in the London borough of Newham. PMID- 2907185 TI - [Comparative studies of clinical findings and prognosis of polyarteritis nodosa, Wegener's granulomatosis, allergic granulomatous angiitis and malignant rheumatoid arthritis]. PMID- 2907186 TI - [Cryptorchism and anti-spermatozoal autoimmunity]. PMID- 2907187 TI - [Clinical importance of the radioimmunologic determination of beta 2 microglobulin in patients with kidney pathology]. AB - High diagnostic significance of beta 2-microglobulin determination by radioimmunoassay in the blood and urine of patients with the main types of renal pathology (chronic glomerulonephritis, chronic pyelonephritis, hemorrhagic fever with the renal syndrome, and diabetic nephropathy) was shown. A study of beta 2 microglobulin level permitted accurate determination of the localization of pathology in the nephron and assessment of a degree of its expression as well as the detection of initial renal functional disorders, assessment of therapeutic efficacy and dynamic observation of renal function in patients with renal pathology. PMID- 2907188 TI - Teratogenicity of the antiallergic Sm 857 SE in rats versus rabbits. AB - Sm 857 SE is an antiallergic drug chemically described as 11-Oxo-11H-pyrido(2,1 b)quinazoline-2-carboxylic acid that has activity against allergic bronchoconstriction in animal models. The purpose of this study was to investigate the teratogenic potential in pregnant rats and rabbits when administered during the critical period of organogenesis. The drug was suspended in aqueous 0.25% carboxymethylcellulose (CMC) solution. Daily doses of 20, 90, or 400 mg/kg were given orally by gavage to rats on days 7 through 17 of gestation and to rabbits on days 6 through 18. Two additional studies were done in rats dosed with 400 mg/kg, and with 90, 200, or 400 mg/kg, respectively. Doses of 20, 90, and 200 mg/kg had no meaningful effects on maternal animals of either species or on their offspring. A dose of 400 mg/kg was maternally toxic in rats as shown by the effects on body weight and food consumption. Among pregnant rabbits, two deaths and three miscarriages occurred at this dose. In rats, 400 mg/kg caused embryonic death, retarded fetal development, and two specific malformations, namely microphthalmia and vertebral-costal defects. A mild teratogenic action of 400 mg/kg also occurred in the first additional study but not in the second one. There was, however, one anophthalmia in a rat fetus of the 90 mg/kg group. In rabbits, no embryotoxic or teratogenic effects were observed. These species differences were explained by the concentration and protein binding in maternal serum as well as by the relatively high concentration of 14C-Sm 857 SE in the rat fetus. PMID- 2907189 TI - A radioimmunoassay for palytoxin. AB - Palytoxin, labelled with 125I-Bolton-Hunter reagent on its terminal amino group, bound specifically to rabbit anti-palytoxin. The extent of binding increased progressively with repeated immunizations. After absorption of the rabbit IgGs with a goat anti-rabbit IgG, binding was reduced greater than 95%. For 50% inhibition of binding in the 125I-palytoxin-antipalytoxin reaction 0.27 pmoles of unlabelled palytoxin was required. Maitotoxin, teleocidin, okadaic acid, debromoaplysiatoxin and 12-O-tetradecanoylphorbol-13-acetate, when tested at 10 100-fold higher concentrations than palytoxin did not affect binding. Palytoxin's serologic activity was stable after 60 min exposure to 100 degrees C and after 60 min exposure to 0.1 N HCl at 50 degrees C, but its capacity to stimulate the arachidonic acid metabolism of rat liver cells was reduced after the 60 min exposure to 0.1 N HCl treatments at 35 degrees C or 0.01 N HCl at 50 degrees C. The average binding constant (K0) as determined by separation of antibody-bound palytoxin from free palytoxin by the double antibody technique was 4.9 x 10(9) M 1 at 0 degrees C. This apparent average association constant increased with increasing temperature suggesting that palytoxin's epitope, most likely hydrophilic, is bound to H2O and the H2O is displaced before binding to the antibody's paratope. PMID- 2907190 TI - Effect of sea nettle (Chrysaora quinquecirrha) venom on isolated rat aorta. AB - The venom from sea nettle (Chrysaora quinquecirrha) (1-10 micrograms/ml) produced an irreversible contraction of the isolated rat aortic ring that was slow in onset, increased with time, and reached maximum in about 10-20 min. The contraction was not inhibited by pretreatment with phenoxybenzamine, atropine, indomethacin, tetrodotoxin, ouabain, low Na+ or Na+-free medium, however, it was markedly decreased by the Ca2+ channel blockers, nifedipine and verapamil. In Ca2+-free medium, no increase in tension was produced by the venom. It is concluded that sea nettle venom causes a contraction of the rat aortic ring by increasing Ca2+ influx through the voltage-dependent Ca2+ channels. PMID- 2907191 TI - Somatic genetic analysis of the expression of cell surface molecules. PMID- 2907192 TI - The molecular genetics of color vision and color blindness. PMID- 2907193 TI - Heads or tails? A homeotic gene for both. PMID- 2907194 TI - neus about c-erb-B-2 and HER2. PMID- 2907195 TI - [Results of the transplantation of free composite flaps to the foot]. AB - The article gives an analysis of results of transplantation of 62 free composite flaps for closing defects of foot soft tissues in 48 patients. Positive results were obtained in 77.4% of the cases. The taking of free composite flaps on the foot greatly depends on the state of the recipient vessels and availability of the pathogenic microflora in the wound. To lean upon the foot was permitted as late as 7-9 months after operation, i.e. after the recovery of surface sensitivity. PMID- 2907196 TI - Effects of streptozotocin-induced experimental diabetes on the morphology and function of the zona fasciculata of rat adrenal cortex. AB - The effects of a severe streptozotocin (STZ)-induced diabetes on the morphology and function of the adrenal zona fasciculata were examined in rats with intact or pharmacologically interrupted hypothalamic-hypophyseal-adrenal axis. In animals with an intact hypothalamic-hypophyseal axis, STZ-diabetes induced hypertrophy of the cells of the zona fasciculata and a rise in the plasma corticosterone concentration. Conversely, in rats in which the hypothalamic-hypophyseal axis had been interrupted, experimental diabetes provoked atrophy of the zona fasciculata cells, and a lowering in the plasma corticosterone level. The effects of STZ diabetes were completely reversed by insulin infusion in both groups of rats. The hypothesis is discussed that the chronic lack of insulin may directly inhibit the growth and steroidogenic capacity of the rat zona fasciculata and that this effect of experimental diabetes may be masked in rats with an intact hypothalamic hypophyseal axis by the concurrent enhancement of ACTH release due to chronic stress resulting from the metabolic consequences of prolonged diabetes. PMID- 2907197 TI - Ultrastructure of perivascular amyloid fibrils in Alzheimer's disease. AB - Perivascular amyloid fibrils in the brains of patients with Alzheimer's disease have been examined by electron microscopy. The amyloid fibrils showed a hollow rod structure and consisted of globular substances. Each turn appeared to be composed of five globular subunits. These findings coincide with the ultrastructure of amyloid fibrils obtained from replicas made by a rapid freezing method. PMID- 2907198 TI - Cell cycle dependent distribution of the proliferation-associated Ki-67 antigen in human embryonic lung cells. AB - The cell cycle-dependent distribution of the proliferation-associated Ki-67 antigen has been evaluated immunocytochemically in L-132 human fetal lung cells. The cells were synchronized and cell cycle phases were determined: G1 = 6.7 h, S = 5.4 h, G2 = 8.5 h and mitosis = 1.3 h. The Ki-67 patterns were strictly correlated with the cell cycle phases. In late G1-phase, Ki-67 antigen was present only in the perinucleolar region. In the S-phase, Ki-67 staining was found homogeneously in the karyoplasm and in the perinucleolar region. G2-phase cells contained a finely granular Ki-67 staining in the karyoplasm with Ki-67 positive specks and perinucleolar staining. In early mitotic cells (pro- and metaphase) an intense perichromosomal Ki-67 staining was observed in addition to a homogeneously stained karyoplasm in prophase, and cytoplasm in metaphase. During ana- and telophase the Ki-67 antigen disappeared rapidly. In resting cells there was no Ki-67 staining. PMID- 2907199 TI - (Neo)glycoproteins as tools in neuropathology: histochemical patterns of the extent of expression of endogenous carbohydrate-binding receptors, like lectins, in meningiomas. AB - Biotinylated (neo)glycoproteins were used to specifically detect endogenous sugar receptors such as lectins in sections of formaldehydefixed, paraffin-embedded tissue from meningiomas. The histochemical methods used consisted of the application of a carrier protein and various covalently linked sugar moieties, available mainly through chemical synthesis, in an optimized standard protocol. They proved valuable in elucidating differential binding patterns within the various meningioma subtypes. alpha-Fucoside-, beta-galactoside-, alpha-mannoside- and beta-xyloside-specific carbohydrate-binding receptors were detected in all the tumor subclasses examined, although the levels of expression exhibited pronounced quantitative differences. In addition, differences in the extent of histochemical staining were observed, using a labelled carrier protein, derived from N-acetylglucosamine and mannose-6-phosphate moieties, respectively. Quantitative differences in the reaction intensity were also measured in the respective subtypes. Receptors for N-acetyl-D-galactosamine were detected only in the analplastic forms, while glucuronic acid-specific receptors were only present in the meningotheliomatous meningioma. In contrast to the other types, malignant meningiomas failed to show cytoplasmic staining with the alpha-glucoside-specific maltose-(BSA-biotin). Distinct differences in the pattern of expression of endogenous sugar receptors, evaluated by a standard protocol, provided further evidence for a possible additional subtype of meningioma, the submalignant meningioma. Our results suggest that labelled (neo)glycoproteins could be used routinely as tools for assessing the expression of endogenous sugar receptors in diagnostic neuro-oncology. PMID- 2907200 TI - Desmin and actin in the identification of Ito cells and in monitoring their evolution to myofibroblasts in experimental liver fibrosis. AB - It has been reported that myofibroblasts contain actin and that Ito cells are positive for desmin. The distribution of desmin and actin detected by immunofluorescence, of vitamin A autofluorescence and of Sudan III staining of lipid droplets has been evaluated in sequential stages of experimental liver fibrosis induced in rats by intraperitoneal injections of swine serum. In the normal rat liver Ito cells were positive for desmin and weakly positive for actin. Prior to the development of hepatic fibrosis a clearcut increase in number and desmin staining of lobular Ito cells was observed in treated rats, but the overall actin pattern was unchanged. In the fibrotic rat livers, highly cellular septa contained large numbers of strongly desmin-positive, actin-weakly positive Ito cells and strongly desmin- and actin-positive myofibroblasts. These observations indicate that both Ito cells and myofibroblasts are positive for desmin, but only myofibroblasts contain large amounts of actin. Visualization of actin and desmin using relatively simple techniques, allows the monitoring of Ito cells proliferation, the accumulation of these cells in fibrous septa and their evolution into myofibroblasts as characterized by their increased desmin and actin content; it also allows an indirect evaluation of the process of fibrogenesis. PMID- 2907201 TI - Effects of partial hepatectomy on microtubules and hepatocellular transport of indocyanine green in rats. AB - The effects of partial hepatectomy on plasma disappearance and biliary excretion of indocyanine green (ICG) have been studied in rats and correlated with morphometric changes of hepatocellular microtubules. The plasma disappearance rate of ICG was in good accord with recovery of liver weight after partial hepatectomy. Biliary excretion of ICG per 100 g liver significantly increased between 3 h and 7 days postoperatively. Colchicine significantly reduced plasma disappearance and biliary excretion of ICG, with no reduction in bile flow, in both intact and hepatectomized rats. Morphometrically, microtubules significantly increased from 3 h following partial hepatectomy and reached a maximum at 24 h with a gradual return to preoperative values at 5 days. These observations suggest that the increased hepatocellular transport of ICG after partial hepatectomy is related to an increase in the number of microtubules. PMID- 2907202 TI - Antitumor effects of endotoxin against solid murine Meth A tumors of different ages. Quantitative histology of the tumors and regional lymph nodes. AB - Mice with 3-, 6-, 9- and 15-day Meth A tumors in the skin were injected intravenously with endotoxin to study age-dependent induction of tumor necrosis and reactive changes in draining lymph nodes. By 24 h after treatment with endotoxin, macroscopic necrosis was seen in 9-day, and to an even greater extent in 15-day tumors; microscopy showed extensive necrosis in 9-day tumors and some necrosis in 6-day tumors. The necrosis was predominantly coagulative, but the 9- and 15-day tumors showed a rim of hemorrhagic necrosis near the skin with surviving tumor tissue located at the lateral and basal margins. All the tumors showed about equal hyperemia by 4 h and mitotic arrest by 4 and 24 h. Depletion of mast cells, which were most numerous in the 9-day tumors, was seen on the dermal aspects by 24 h. Endotoxin did not change the morphology of the lymph nodes and disseminated tumor cells within 24 h. Endotoxin is known to cure 9-day Meth A tumors, and the extent of the rapid necrosis induced is clearly the crucial factor. Necrosis, however, is not a direct consequence of early hyperemia or mitotic arrest and other factors related to the age and site of the tumor, apparently affect whether or not necrosis ensues. PMID- 2907203 TI - Histopathological characteristics of the kidney in recombinant inbred mice established from MRL/lpr x AKR crossing. Dissociation of severity of lupus nephritis from the degree of lymphadenopathy. AB - Recombinant inbred (RI) lines were established from (MRL/lpr x AKR) crosses in order to analyze the role of the lpr gene and the participation of background genes in the lymphoproliferation and the development of lupus glomerulonephritis (LGN). In this study, six lines were used to compare with MRL/lpr and AKR mice. Lymphadenopathy was present in four lines (A-22, A-31 b, A-31 e and C-12) but absent in the other two (A-21 and C-21). The degree of lymphoproliferation varied between individuals of the RI lines showing lymphadenopathy. On gross examinations, the most marked lymph node enlargement was seen in the A-31 b line, which resembled MRL/lpr mice in this respect; lymphadenopathy was least prominent in the C-12 line and intermediate degrees occurred in the A-22 and A-31 e lines. Like MRL/lpr mice, deaths in the RI lines were due to LGN; however, in the lines with lymphadenopathy, 50% mortalities occurred a few weeks later than in MRL/lpr mice. The kidneys were examined histologically for proliferative, exudative, extracapillary and membranous changes in the glomeruli. The glomerular lesions in the A-22, A-31 b and A-31 e lines closely resembled those in MRL/lpr mice, but in the C12 line in which lymph node enlargement was least apparent, the histological abnormalities were significantly more severe. Of the lines without lymphadenopathy, histopathological examination showed obvious renal abnormalities in the A-21 line but none in the C-21 line or in AKR mice. From these findings it appears that there are autosomal genes which affect the expression of the lpr gene and thus modify the development of LGN and lymphoproliferation. PMID- 2907204 TI - Vimentin and glial fibrillary acidic protein are codistributed in the same intermediate filament system of malignant glioma cells in vivo. A double-labeling immunoelectron-microscopical study. AB - Normal, reactive, and neoplastic astrocytes express two types of intermediate filament (IF) proteins, namely glial fibrillary acidic protein (GFAP) and vimentin. Their submicroscopical distribution in vivo is so far unknown. We therefore investigated four malignant gliomas by electron microscopy, applying postembedding double immunogold labeling. The IF proteins were randomly scattered over the same filament bundles, as in previous experiments on glioma cultures. No clustering or preferential intracytoplasmic location of either IF protein was visible. The demonstration of IF proteins within nuclei gives some support to the suggested intranuclear functions of IF proteins. PMID- 2907205 TI - Sensitive detection and typing of human papillomavirus DNA in gynecological cell scrapings by slot-blot hybridization. AB - A rapid and sensitive method for detecting and typing human papillomaviruses (HPVs) in cell scrapings is presented. DNA from scrapings is extracted and bound to nitrocellulose filters (Slot-Blot). By DNA-DNA hybridization with specific 32P labelled HPV-probes (types 6/11 or 16/18) the patient's DNA is then analyzed for the presence of, and for the type of, HPV DNA sequences. A parallel hybridization with a human repetitive element (Alu sequence) allows quantitation of the different hybridization results. Experiments with HeLa cell DNA show that as little as 10(4) HPV sequences can be detected and typed specifically with this test. Evaluation of this test is completed within 6 to 7 days after cell collection. This Slot-Blot method was used to analyse 1330 specimens taken at the Bernese Dysplasia Outpatient Clinic. The results reveal a very high percentage (90%) of HPV-positive cases in the patient group examined. PMID- 2907206 TI - Identification and characterization of a human cell line with dendritic cell features. AB - CORP-4 is a cell line obtained in our laboratory from an explanted human bladder carcinoma. This cell line shows certain dendritic cell features such as adherence to the culture plate surface, a doubling time of 24 h and an enzymatic profile typical of cells involved in antigen presentation (non-specific esterases, lysozyme and alpha-1-antitrypsin). Its phenotypic analysis revealed CD 15 and Fc receptor expression, S-100 surface protein and the presence of positive reactivity to different lectins such as Concanavalin A (Con A) and Peanut agglutinin (PNA). CORP-4 was found to be a non-phagocytic cell line after it was assayed with latex, and FcR- and C3bR-mediated phagocytosis. Furthermore, CORP-4 produced interleukin-1 (IL-1) as determined by thymocyte proliferation assays and also fixes immune complexes in a non-complement dependent fashion. HLA class I and class II antigens were inducible by both 5 azacytidine and gamma interferon. PMID- 2907207 TI - Plasma membrane shedding and colloid vacuoles in hyperactive human thyroid tissue. AB - The ultrastructural appearance of colloid vacuoles, considered to be a typical sign of hyperactivity in the human thyroid gland, was studied in human thyroid tissue transplanted to nude mice and in human thyroid tissue fixed directly after surgical removal in patients with thyrotoxicosis. Transplanted normal thyroid tissue and toxic diffuse goiter (TDG) tissue was fixed by vascular perfusion with glutaraldehyde 5 or 12 weeks after transplantation. Light microscopic quantification showed that daily injections for 2 weeks of a gamma globulin fraction of patient sera containing thyroid-stimulating immunoglobulins (TSI) greatly increased the number of colloid vacuoles in both types of transplants. The vacuoles were mainly located in the periphery of the follicle lumen, giving the colloid a scalloped appearance. Electron microscopy of TSI-exposed tissue revealed, in addition to colloid vacuoles, the presence of large amounts of membrane material in the follicle lumen. Only sparse amounts of intraluminal membrane material were present in controls. The colloid vacuoles were almost invariably associated with such membrane material, which lined the border between the vacuole and the surrounding colloid. The intraluminal material consisted of spherical and elongated formations, each structure limited by a triple-layered membrane and often containing a dense interior. The elongated structures were often of the same dimensions as microvilli. The apical surface of follicle cells in TSI-exposed tissue expressed numerous microvilli, of which many showed a similar dense interior as the intraluminal membrane structures. The intraluminal membranes frequently showed, like the apical plasma membrane of the follicle cells, a positive reaction for peroxidase. Organelles, such as mitochondria, lysosomes or rough endoplasmic reticulum, were not encountered among the intraluminal membrane structures. These observations indicate that the intraluminal membrane material is derived from the apical plasma membrane of the follicle cells, presumably by shedding of microvilli. A similar association between colloid vacuoles and membrane material was also found in thyroid tissue from patients with thyrotoxicosis fixed directly at operation. It is suggested that the presence of membrane material in the follicle lumen precipitates the formation of colloid vacuoles in hyperactive thyroid tissue. The possible involvement of intraluminal membrane material in the development of microsomal autoantibodies in Graves' disease, i.e. exposure and presentation of thyroid microsomal antigen (identical to thyroperoxidase) to the immune system, is discussed. PMID- 2907208 TI - Evaluation of polysialic acid in the diagnosis of Wilms' tumor. A comparative study on urinary tract tumors and non-neuroendocrine tumors. AB - The polysialic acid moiety of the neural cell adhesion molecule has been shown to represent an onco-developmental antigen which can be detected in both embryonic human kidney and Wilms' tumor but not in normal adult human kidney. In the present comparative study, Wilms' tumors, clear cell (bone-metastasizing) sarcomas of kidney, cystic nephromas, renal cell carcinomas, transitional cell carcinomas and papillomas of the renal pelvis, ureter and urinary bladder (as well normal transitional epithelium from these regions). Ewing sarcomas, hepatoblastomas, rhabdomyosarcomas, and carcinomas of the stomach, colon, exocrine pancreas, lung, and esophagus, were investigated immunohistochemically for the presence of polysialic acid. In addition, immunoblot analysis was performed in selected tumors. With the exception of Wilms' tumor, none of the tumors investigated was positive for polysialic acid. In Wilms' tumor, blastemal cells and all epithelial components were positive but no immunostaining was observed in the stroma. These observations emphasize the potential value of a monoclonal anti-polysialic acid antibody in identifying blastemal metanephric cells and their epithelial differentiatives in Wilms' tumor. PMID- 2907209 TI - Heterogeneity of BamHi DNA fragments B and E in several HSV-1 strains and recombinants. AB - The restriction cleavage sites of the BamHI-B and BamHI-E DNA fragments of several Herpes simplex virus type 1 (HVS-1) strains were mapped. These fragments are situated at the ends of the long unique regions and share homologous sequences in the repeat components (TRL and IRL) of the genome. All the strains analyzed were found to have deletions in the Hpal-P fragment, situated in the BamHI-B fragment. Five strains were further analyzed and the deletions were located in the Smal-A fragment (within the Hpal-P fragment). The BamHI-E fragment of four recombinants (obtained by recombination between the HFEM genome and the BamHI-B fragment or part of it from the HSV-1 F strain) were almost identical but differed from another strain [NIH(LP)]. Comparison of the BamHI-B and the BamHI-E fragments of the same strain revealed that the fragments were not identical in all cases. PMID- 2907210 TI - [Altered gamma-glutamyltransferase, aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase serum activities in long-term anticonvulsive therapy--comparison of diphenylhydantoin and carbamazepine]. AB - In 110 patients receiving a long-term anticonvulsant monotherapy with Diphenylhydantoin (DPH) and Carbamazepine (CBZ) the serum activities of gamma-GT, ASAT, ALAT, and AP were examined retrospectively. Elevated serum levels of enzymes were seen predominantly concerning gamma-GT and AP. 91% resp. 39% of patients receiving DPH-therapy showed increased gamma-GT resp. AP-levels compared to 64% and 14% of gamma-GT and AP-elevations by CBZ-treatment. All enzymes evaluated were more often and higher elevated by DPH than CBZ. Frequency and extent of increased activity of gamma-GT were highly related to daily dosage in both preparations. The proportion of pathological enzyme levels was associated with age in DPH and CBZ as well but not found to be significant. Sex differences in the frequency of increased enzyme activities could not be demonstrated. The results are discussed in the context of induction of cytochrome P-450-system. PMID- 2907211 TI - [Excretion of the urinary enzymes alanine aminopeptidase and beta-glucuronidase in cystostatic perfusion therapy]. AB - Following cytostatic perfusion therapy in patients with malignant melanoma of the lower extremity despite a separation of the regional circulation from the systemic circulation a rhythmically phase-like increased excretion of urinary enzymes and protein developes. The changes in the behaviour of the excretion of enzymes registered under tumour therapy without a simultaneous reaction of usual functional parameters emphasize the importance of the urinary enzymes as early phase parameters. In this study the urinary enzymes were used for the judgement of the systemic effect of the cytostatic perfusion therapy. PMID- 2907212 TI - [Cell membrane changes and skin diseases]. AB - Biological membranes are laminar bilayers of lipoids with thermolabile biophysical properties. Changing temperatures not only result in altered polarity and permeability of the membranes, but also in changes of the various membrane receptors (e.g. histamine and beta-adrenergic receptors) and the cell makers. In healthy persons, lower temperatures (25 degrees) lead to elevated suppressor properties, and the T4 ratio is below 1.0. At 37 and 41 degrees C, there is a growing number of helper cells, and the T4/T8 ratio becomes normal again. In psoriatic patients, the number of helper cells does not change with the temperature. We also found some evidence for changes of the cell membranes in atopic dermatitis and chronic urticaria. PMID- 2907213 TI - [Follow-up study of 48 athletes with stage I hypertension with and without pharmacotherapy]. AB - We found in an earlier investigation that the frequency of hypertension is considerably lower among male athletes than in a random sample of the general population. The cases of hypertension in younger athletes are primarily hypertension stage I (WHO). We followed up on the question of the course of hypertension stage I and the possibility of spontaneous remission. For this, we observed 28 nonmedicated patients with hypertension stage I for 4.2 +/- 2.3 years, 20 patients undergoing drug therapy for 2.5 +/- 1.3 years, and 12 healthy athletes for 4.2 +/- 2.2 years. Under drug therapy, as expected, there was a normalization of both basic and exercise blood pressures. Fifty percent of patients without drug therapy showed remission of the elevated basic and exercise pressures after 2 to 3 years; 50% had an unchanged high pressure or deterioration. The transition of hypertension WHO stage I to stage II with regard to left ventricular hypertrophy could be ruled out echocardiographically in patients with a favorable course (remission). However, there was a tendency in this direction among patients with the least favorable course. PMID- 2907214 TI - [Complex problem solving in adolescents with disorders of brain function]. PMID- 2907215 TI - [The development of the ideas of A. D. Speranskii on the means for the realization of the trophic function of the nervous system]. PMID- 2907216 TI - [The chemical link in the pathogenesis of organic brain lesions]. PMID- 2907217 TI - [The nervous system and immunity]. PMID- 2907218 TI - [Neurogenic immunodeficiency]. PMID- 2907219 TI - [The combined therapy of gonorrhea and gonorrheal-chlamydial infection in patients who abuse alcohol]. PMID- 2907220 TI - [The status of Churg-Strauss syndrome among other hypereosinophilic, granulomatous and vasculitic diseases]. AB - The Churg-Strauss syndrome is a disorder characterized by hypereosinophilia and systemic vasculitis occurring in patients with asthma and allergic rhinitis. Only few patients are identified as having this syndrome. The three histological criteria are necrotizing vasculitis, tissue infiltration by eosinophils, and extravascular granulomas; they often do not coexist in one patient. To find a clinical approach to diagnosis, it is necessary to exclude other disorders with hypereosinophilia, granulomas, and vasculitis. In regard to this clinical viewpoint it seems that the syndrome is not as rare as may be assumed according to the relevant autopsy findings. Two cases are reported in which the Churg Strauss syndrome developed together with rheumatoid arthritis; in one case it was likely triggered by treatment with D-penicillamin. PMID- 2907221 TI - [Detection of dipeptidyl peptidase IV in follicular fluid--initial report]. AB - Aspirates of ovarian follicles were obtained from patients subjected to gynaecologic surgeries. This is the first report of dipeptidyl-peptidase IV (DP IV) activity in human follicular fluid. This enzyme specifically cleaves regulatory important oligo- and polypeptides. Only from peptides with proline or alanine in position P1 of the N-terminal sequence a dipeptide is split off. DP IV activity was measured with glycyl-L-proline p-Nitroanilide as substrate. Levels in a range of 209.8 +/- 57.4 nmol l-1 s-1 were achieved. PMID- 2907222 TI - [Nonclostridial anaerobic infections of the central nervous system]. PMID- 2907223 TI - Changes in the drug treatment of chronic congestive heart failure. PMID- 2907224 TI - Clostridial gas gangrene: a review of 48 consecutive cases. PMID- 2907225 TI - Pathologic myopia and pharmaceutical agents: rheo-oculographic experience. PMID- 2907226 TI - Regulation of local blood flow by neurohumoral substances released from perivascular nerves and endothelial cells. PMID- 2907227 TI - The role of the kidney in neurohormonal cardiovascular regulation. PMID- 2907228 TI - Neurohumoral circulatory regulation in hypertension. PMID- 2907229 TI - The importance of the subepithelial resistance for the electrical properties of the rat jejunum in vitro. AB - The aim of the study was to evaluate full-thickness and partially stripped jejunum as a model for neurogenic control of electrogenic ion transport. The electrical properties of full-thickness and partially stripped segments were studied in Ussing chambers. Using square-pulse analysis, subepithelial and epithelial resistances (Rs and Rp) were determined, and by compensating for the potential fall across Rs, the current generated by the epithelium could be measured. In full-thickness tissue, Rs was approximately 80% of total tissue resistance, and the current measured during short-circuiting of the whole tissue (SCC) was therefore only 20-25% of the current generated by the epithelium (Im). Surgical stripping of the tissue decreased Rs by 10-20%. This means that in full thickness as well as in stripped tissue, 70-80% of the potential difference across the epithelial layer remains after traditional 'short circuiting'. Over a 25-min period, none of the electrical parameters changed significantly in the full-thickness tissues. In the stripped group PD, SCC and Im fell significantly, and in parallel during the same period of time. Neither glucose, noradrenaline, met-enkephalin or carbachol had any significant effect on Rs, Rp or the Rs/Rp ratio. The relative effects of these agents on Im and SCC were therefore similar. Substance P and VIP increased the Rs/Rp ratio significantly and, therefore, the effect of these drugs on Im was significantly more pronounced than the effect on SCC. The results show that the subepithelial resistance must be taken into account when the electrogenic activity in the epithelium is to be determined correctly. Conventionally measured SCC reflects the electrogenic effect of the tested putative neurotransmitters, but the magnitude of the responses is grossly underestimated, particularly for substance P and VIP. PMID- 2907230 TI - [Work psychopathology]. AB - Work psychopathology concept is outlined, restricted, however, to different disorders and conflicts whose actual cause is to be found in the intrinsic mechanism of work-related activity. Environment- and life condition-related causes are disregarded. Nervous fatigue neurasthenoid syndrome is understood as a result of a dephasing between CNS neurophysiological timing and work rhythms. The author stresses that taking productivity as a parameter for nervous fatigue measurement--which substituted for the former muscular fatigue criterion in industry--is quite erroneous an opinion. Ergonomy is to be developed: Ergonomy is an interdisciplinary science which studies concordance between Man's physical and psychophysiological possibilities and properties, and possibilities and properties of contemporary work technical systems and their functioning conditions as well. PMID- 2907231 TI - Imaging of the stomach, and localization of the stomach meridian & its acupuncture points in a human cadaver by the use of the indirect "Bi-Digital O Ring Test Imaging Technique". AB - Since 1984, using the "Bi-Digital O-Ring Test (Molecular Identification, Localization and) Imaging Technique" originally developed by Y. Omura, the imaging of the outline of normal and abnormal internal organs has been successfully applied for clinical diagnosis and evaluation of therapeutic effects, without the use of expensive imaging instrumentation. Not only has it become possible to non-invasively image each internal organ and localize specific malignant tumors of specific internal organs, as well as neurotransmitters, but it has also recently become possible to demonstrate the presence and exact locations of the meridians corresponding to specific internal organs and their acupuncture points along the meridians through the use of either the Direct or Indirect "Bi-Digital O-Ring Test (Molecular Identification, Localization and) Imaging Techniques" while holding a microscopic slide of the specific human internal organ tissue. However, very little information was available to demonstrate the presence of the meridians and their acupuncture points in a human cadaver. In this study, we were able to demonstrate by use of the Indirect "Bi Digital O-Ring Test (Molecular Identification, Localization and) Imaging Technique" the presence of meridians corresponding to specific internal organs and acupuncture points on the meridians, all of which were nearly identical to those found in a living human. For example, the authors found that the stomach meridian at both ends of one of the most well-known acupuncture points, Stomach 36, is located within 1 mm of the surface of the skin, and the average diameter of the meridian is less than 1 mm. Stomach 36 in this particular cadaver had a round shape with a diameter of approximately 1.8 cm at the skin surface. The acupuncture point, St. 36, in this cadaver at the skin surface was round in shape and extended to the deepest underlying muscle layer of the tibialis anterior muscle, in three dimensions. In spite of the fact that the Indirect Bi-Digital O Ring Test Imaging Technique showed a distinct pathway for the stomach meridian and the location of St. 36, there was no apparent difference to the naked eye between the meridian and the surrounding non-meridian tissue, nor between St. 36 and surrounding non-acupuncture point area. However, there seems to be a more dense connective tissue network between the skin layer and the fascia on the muscle tissue at the acupuncture point, as compared with the surrounding non acupuncture point area.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2907233 TI - 4th annual International Symposium on Acupuncture and Electro-therapeutics. October 13-16, 1988, New York City. Abstracts. PMID- 2907232 TI - Promoted healing of leprous ulcers by transcutaneous nerve stimulation. AB - Low-frequency (2 Hz) transcutaneous electrical nerve stimulation (TNS) may produce widespread and prolonged increases in skin temperature in patients with peripheral vascular insufficiency due to improved microcirculation. The method has previously been used successfully to potentiate healing of chronic ulcers of various etiology. The present report describes a similar study, using TNS treatment in attempts to accelerate healing of chronic leprous ulcers that had resisted treatment for several months or years. All other treatment, local and systemic chemotherapy, and daily regime remained as far as possible unaltered. The study was limited to ulceration in the soft tissue of the foot or lower leg. Eleven TNS sessions, each of 30 min duration, were applied per week. In 19 patients (6 out- and 13 in-patients), in whom the TNS treatment was not interrupted, all ulcers healed completely within a mean of 5.2 weeks (range 3-12 weeks). The mean size of the ulcers was 5.2 cu.cm (range 0.2-48.3 cu.cm), and they had persisted for a mean of 15.8 months (range 2-60 months). The 'healing index', i.e. the mean reduction of the ulcer cavity per week, was 1.0 cu.cm/week. The study demonstrates a clear therapeutic effect for low-frequency TNS in patients with leprous ulcers. The mechanisms involved in the accelerated healing are assumed to be increased microcirculation due to sympatho-inhibition and release of endogenous corticosteroids. PMID- 2907234 TI - Reoperations and the internal mammary artery. PMID- 2907235 TI - Multiple bradykinin receptors: results of studies using a novel class of receptor antagonists. PMID- 2907236 TI - In vitro studies on relationships between muscarinic receptors and somatostatin in the rat brain. PMID- 2907237 TI - In vivo PET and SPECT receptor imaging: new technology and tactics for receptor measurement. AB - PET and SPECT approaches to radiolabelled neurotransmitter receptors provide a new and complimentary tool to existing receptor and neurotransmitter studies. They provide information which will extend other current in vitro and in vivo non imaging procedures while likely requiring the types of resolution and sensitivity which are possible with the latter methods to help in the interpretation of the PET studies. PMID- 2907238 TI - Interactions between neurotransmitters that regulate cAMP and intracellular Ca2+ levels in the CNS. PMID- 2907239 TI - Changes in apparent functions of component proteins of adenylate cyclase system in rat brain by drugs acting on the central nervous system. PMID- 2907240 TI - Histaminergic neuron system and its function. PMID- 2907241 TI - [The femoro-patellar joint and cartilage damage of the knee joint]. AB - This article surveys the update knowledge of diagnosis and treatment of damage to the cartilage with particular reference to the femoropatellar joint. Complementary to this the biomechanical fundamentals and special anatomic features are explained, the knowledge of which is imperative for an understanding of the complex linkups and interconnections. PMID- 2907243 TI - [The effect of primary nailing on the immediate fate of patients with femoral neck fractures]. AB - Based on their 494 own cases with femoral neck fractures authors investigate the impact on time elapse between the injury and the osteosynthesis upon the outcome of these patients. By comparing two groups with equal severity it was concluded that an operation within 6 hours after the injury is favourable both with regard to the mortality and the systemic or local complications. They provide an explanation for the good results through the analysis of their cases and give a brief review of the literature on this subject as well. PMID- 2907242 TI - [3 years experiences with the dynamic hip compression screw]. AB - The authors report on 140 cases of fractures near the hip joint, which had been treated by applying a dynamic hip compression screw (DHS). DHS is an ideal method for stabilising pertrochanteral stable and lateral fractures. In unstable pertrochanteral fractures it is recommended to use a 130 degrees or 150 degrees DHS, depending on the age and the patient's preoperative ability to walk. In medial fractures of the neck of the femur the use of DHS offers no advantage compared with screwing or total endoprosthesis. The article reports on the postoperative results. In respect of these results DHS appears to be superior to fracture nailing according to Ender. PMID- 2907244 TI - [Stable osteosynthesis following ilial resection in intraosseous Ewing sarcoma]. AB - A case of a young man with Ewing's sarcoma of the os ilium is demonstrated. The tumor is removed by resection of the os ilium and the adjacent musculature. The bony stability is reconstructed by means of a double autogenous free fibula graft in combination with a broad plate, braced between os sacrum and the roof of the acetabulum. Full weight bearing is possible, at present there is no evidence of a local recidive or of metastases. PMID- 2907245 TI - [Distal biceps tendon rupture. Clinical aspects--therapy--results]. AB - Between 1980 and 1986 16 male patients of between 30 and 65 years of age were treated operatively because of distal biceps tendon ruptures. The operative procedures are reported and the results of a follow-up examination two years later are communicated. The good results of the applied operative treatment allow to recommend the operative procedure. A special method of measurement of muscle power is presented. PMID- 2907246 TI - [Significance of microsurgery revascularized soft tissue and bone transplants in plastic reconstructive interventions of the extremities]. AB - By using the fixateur externe in the fixation of bone fractures in the presence of heavily damaged soft tissue, we now have to tackle the challenge of adequate soft tissue coverage besides osteosynthesis of bone fracture. Free microvascular tissue transfer now increasingly replaces the previous method of management in which the soft tissue was reconstructed step by step. This technique is undoubtedly the solution for a lot of earlier problems, but now other questions have come up, particularly regarding time for tissue transfer. The article reports on the experience collected by us. PMID- 2907247 TI - [Clinical experiences with tetrachlorodecaoxide in the local treatment of difficult-to-heal wounds]. AB - Local treatment of difficult wounds with TCDO, a chemically stable, water-soluble compound containing oxygen in a chlorite matrix, is supposed to increase the pO2 in hypoxic wound tissue and to amplify physiological responses of phagocytes in wounds. 21 patients were assigned to two groups, treated by TCDO impregnated dressings twice a day or by TCDO combined with temporary skin coverage Epigard. Daily records of the state of the wounds with regard to exudation, wound cleansing, formation of granulation tissue and epithelisation demonstrated the therapeutic effect of TCDO in the treatment of complicated wounds when primary surgical debridement was sufficient. PMID- 2907248 TI - [Initial clinical experiences with low molecular weight heparin in the prevention of thrombosis in orthopedic surgery]. AB - This is a report on almost 10 years of experience with heparin prophylaxis in orthopaedic surgery, especially on the changeover from the high molecular heparin dihydergot used previously, to the low molecular heparin dihydergot (Embolex) while changing over at the same time from the previously well-tried and successful postoperative initiation of treatment to preoperative start of prophylaxis. Compared with the period before prophylaxis (1965-1977) with 24 fatal pulmonary embolisms, no fatal pulmonary embolisms have occurred in our hospital since prophylaxis was introduced (1978). Changeover to low molecular heparin with only one instead of three injections daily was fundamentally welcomed although preoperative onset of prophylaxis involved a considerable rise in afterbleeding complications. Hence we recently adopted the procedure of conducting prophylaxis with low molecular heparin (as was done previously with success using high molecular heparin) postoperatively; this resulted in a dramatic reduction of bleeding complications while protection against thrombosis is obviously clinically satisfactory. Postoperative initiation of prophylaxis is therefore recommended in case of major orthopaedic surgery. PMID- 2907249 TI - [Prevention of cement extravasation into soft tissues in compound osteosyntheses]. PMID- 2907250 TI - [Computerized tomography findings and the clinical course in infratentorial trauma]. AB - Clinical examination of severe brain injuries often suggests involvement of the brain stem and pontine structures not only via functional but also via structural lesions. Computer tomographic evidence of infratentorial trauma, however appears comparably rarely. 32 of 436 brain injured patients examined by CT showed traumatic infratentorial lesions. We examined these patients with regard to the distribution of structural damage, place of primary impact of force, incidence of skull fractures and accompanying supratentorial injuries, initial clinical status and clinical outcome. All but 2 patients were primarily unconscious. The lethal outcome in 7 patients was presumably due to the traumatic involvement of supratentorial structures. Patients with mainly infratentorial lesions--even with large epidural haematoma--showed a good recovery and fair rehabilitative outcome if the operation was performed immediately. PMID- 2907251 TI - [The post-burn process--a determinant in local surgical treatment of deep burns]. AB - Afterburning has been studied in the animal experiment by use of intravital dye indicators and by measuring partial oxygen pressure. After third degree burn the oxygen conduction of the damaged skin increased. The afterburning was seen to be finished on the 5th day after the burn trauma. The histological changes in the depth of the afterburn area reaches to the subcutis. The extend of the afterburn area was not related to the applied temperature or the duration of the experimental burn injury. PMID- 2907252 TI - [Changes in pressure and contact surface of the talar joint surface in various foot angle positions and following stepwise division of the fibular ligaments--an experimental study]. AB - Pressure and area of contact curves of the ankle joint were determined in various degrees of flexion and with the external ligaments in different states of severance or division, using five ankle joint preparations as basis. The largest contact area and most uniform pressure distribution were seen if the ankle was in normal position and at a plantar flexion of five degrees. After injury of the external ligaments there was either a reduction of the area of contact associated with a pressure increase, or an increase of the area of contact associated with an inhomogeneous pressure distribution. The greatest loss in area of contact and pressure increase occurred after lesion of the fibular ligaments in supination and supination/plantar flexion of the foot. The moment of rotation for supinatory forces applied to the margin of the foot, increased continuously in that case. PMID- 2907253 TI - [Results of biomechanical studies of various external fixation devices of the pelvis]. AB - Various mounting systems used in fixation of the pelvis were tested for their stability. The systems were mounted on macerated pelvices and their firmness examined. The criterion for the examination was on the one hand the force needed under distraction to cause a distension in the region of the symphysis or of the sacroiliac joint of 1 cm., on the other hand the force needed to tilt the disjunction points for 1 cm. when shearing takes place. It was concluded from the study that in clinical use, given unstable pelvic fractures, mountings applied only anteriorly are not capable of withstanding the strain expected under biological conditions. Consequently, mobilisation with full weight bearing in instable pelvic fractures is not possible in a shorter period of time than with conservative (extension) treatment. PMID- 2907254 TI - [Late results of surgical management of medial femoral neck fractures by spongiosa traction screws]. AB - In 36 cases of medial fracture of the femoral neck percutaneous compression osteosynthesis by a specific traction-screw was carried out. During a 3-year follow up five femoral head necroses and three cases of non-union occurred. 28 patients showed good or excellent results. Comparison with results of AO spongiosa screws and sliding-screw plate reveals no significant differences. Due to small additional operative trauma this percutaneous fixation technique is an appropriate alternative of osteosynthesis of medial fractures of the femoral neck, especially in polytraumatised patients and old patients with high operative risk. PMID- 2907255 TI - [Abduction fractures of the femur neck in adolescents]. AB - Valgus fractures of the femoral neck during growth are a rarity. Four cases are reported, and, in addition, one patient from the literature. Three were treated by bed rest, two by primary screw fixation. Clinical results were good; there was no necrosis. In accordance with the experience with similar fractures in adults primary osteosynthesis is recommended in all cases to prevent secondary displacement. Decompression of the hip joint by aspiration should be done for diagnosis and for decompression of tension haemarthrosis. PMID- 2907256 TI - [Bilateral intra-ligamentous traumatic rupture of both patellar tendons--a case report]. AB - The authors report on a rare case of a bilateral intra-ligamentous rupture of the patellar ligaments and describe their technique of reconstruction. Special emphasis is given to the correct adjustment of the length of the patellar ligament. PMID- 2907257 TI - [Dorsal dislocation of the metacarpophalangeal joint of the index finger]. AB - The author reports on a dorsal dislocation of the metacarpophalangeal joint of the index finger. This type of lesion is relatively rare. Reduction is easy in incomplete dislocation, but the complete dislocation requires surgical intervention. PMID- 2907258 TI - Human monkeypox: confusion with chickenpox. AB - Human monkeypox is a zoonosis occurring sporadically in the tropical rain forest of western and central Africa. The exact incidence and geographical distribution are unknown, since many cases are not recognized. Special surveillance was established in three regions in Zaire in 1981 that led to a substantial increase in reported cases. The question arose as to the possibility that clinical diagnostic errors cause some cases of monkeypox to be misdiagnosed as other eruptive diseases. This paper presents the results of a study assessing the extent of and reasons for these clinical diagnostic errors in areas where health staff as well as the general public are aware of human monkeypox. In Zaire in the period 1981-1986, 977 persons with skin eruption not clinically diagnosed as human monkeypox were laboratory tested. 3.3% of human monkeypox cases were found among 730 patients diagnosed as cases of chickenpox, 7.3% among cases diagnosed as "atypical chickenpox" and 6.1% among cases with skin rash for which clinical diagnosis could not be established. The diagnostic difficulties were mainly based on clinical features characteristic of chickenpox: regional pleomorphism (in 46% of misdiagnosed cases), indefinite body-distribution of skin eruptions (49%), and centripetal distribution of skin lesions (17%). Lymph-node enlargement was observed in 76% of misdiagnosed patients. In the absence of smallpox, the main clinical diagnostic problem is the differentiation of human monkeypox from chickenpox. The presence of lymphadenopathy, pre-eruptive fever and slower maturation of skin lesions are the most important clinical signs supporting correct diagnosis of monkeypox. PMID- 2907259 TI - Serodiagnosis of African sleeping sickness in vervet monkeys by detection of parasite antigens. AB - Sera of vervet monkeys experimentally infected with T. b. rhodesiense were examined using a double antibody sandwich ELISA and Procyclic Agglutination Trypanosomiasis Test (PATT) for the presence of circulating trypanosomal antigens and anti-procyclic surface antibodies, respectively. Trypanosomal antigens were detected at 7 days post infection and remained at a detectable level thereafter during the infection. Antigens were not detected in sera prior to experimental infection or at 26 days after trypanocidal drug treatment. Although both the PATT and the sandwich ELISA results correlated with the infection status of the animals, the sandwich ELISA gave a better indication of the disease progression than the PATT, especially during trypanocidal drug therapy. The results illustrate the potential utility of the double antibody sandwich ELISA for diagnosis of African sleeping sickness. PMID- 2907260 TI - [The use of sentinel animals for the evaluation of the control of vectors of sleeping sickness: preliminary reports at a Congolese site]. AB - A large-scale control trial against Glossina palpalis palpalis was carried out in the Congo using a new trapping technique. In the same way a test related to the experimental utilization of sentinel animals was performed, concurrently to the classical epidemiological and entomological evaluation. 564 domestic animals (pigs, sheep, goats) were examined parasitologically (wet blood films, Woo/HCT) and serologically (Testryps CATT) in six villages. When a drastic reduction of tsetse populations was achieved (i.e. zero point of apparent density) a parasitological negativation was first noted after one year and a complete serological negativation was observed after two years. If only a relative decrease in the vector's apparent densities occurred, it was related with a lower of sero-parasitological prevalence rate. The use of a serological test which was able to detect Trypanosoma congolense antibodies as the Testryp CATT, is a particularly useful technique for estimating the animal transmission level. These first results give some arguments that a parasitological and serological continuous of sentinel animals as pigs and sheep is a useful mean for evaluating the efficiency of a control campaign against sleeping sickness vectors. PMID- 2907261 TI - The feeding habits of the tsetse, Glossina pallidipes Austen on the south Kenya coast, in the context of its host range and trypanosome infection rates in other parts of east Africa. AB - The results of blood-meal identifications for 651 Glossina pallidipes from 5 subpopulations near the Kenya coast south of Mombasa, and one, 70 km inland, are presented. Bushpigs and/or warthogs were important hosts for G. pallidipes at all sites. Other major hosts included elephant, buffalo and bushbuck where they were present, and on a dairy ranch nearly 30% of feeds were taken from cattle. There was a general relationship between the numbers and diversity of wild herbivores and the abundance of G. pallidipes. These results are discussed in relation to published data on feeding patterns and trypanosome infection rates for G. pallidipes from other parts of East Africa. Overall, there are significant correlations between the proportions of bovid feeds and T. vivax infections. Bovid-feeding G. pallidipes populations with high T. vivax infection rates in south-east Uganda and western Kenya contrast with the coastal, suid-feeding populations with low T. vivax rates. These characteristics are presented as clines extending across East Africa. PMID- 2907262 TI - [An ecologic study of adult and larval Culicidae in a rice field of Kou Valley, Burkino Faso]. AB - An entomological survey based on collections of human bait mosquitoes and of mosquito larvae was carried out through one year in a rice-field, the Kou Valley of southwest Burkina Faso. Each year, in this irrigated rice field there are two crops of rice, one during the dry season and another during the wet one. Between the two rice cycles irrigation is interrupted and the rice field becomes dry. The rice crop cycle moves through several stages, all of which have positive or negative effects on the development of the larvae of most abundant mosquitoes species. Rice cultivation does not explain however entirely the ecology of mosquito populations. Two main limiting factors for mosquito development are highlighted: the season with two periods (1. dry, 2. wet) and the rice cultivation with three periods (1. start of the flooding, growing rice transplantation and tillering, 2. rice heading and flowering, 3. rice maturation and harvest). The development of a majority of mosquito species depends strictly on rice growth: (i) Anopheles gambiae s.1. uses the whole rice field during the first period of rice cultivation until growing rice protects the larval breeding places from solar radiation. It is the most frequent mosquito (53% of the man biting mosquitoes caught). 5% of its larvae are parasitized with a fungus Coelomomyces sp., (ii) A. pharoensis has its maximum density during the second period of rice cultivation, as Culex gr. decens; both seem to succeed better in the dry season, contrary to all other anophelines, (iii) A. coustani profits by the third period when the pH of the breeding places becomes basic.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2907263 TI - Antibody response against Litomosoides carinii and the distribution of bound antibodies on microfilariae from the different internal organs of cotton rats. AB - The courses of IgG and IgM antibody levels against adult worm and microfilarial antigen were determined in isogenetic cotton rats infected quantitatively with Litomosoides carinii. Against both antigens, IgG as well as IgM, antibody levels exceeded significantly those of noninfected animals, and the IgG levels were generally higher than the IgM levels. The total antibody production was depressed transiently 8 weeks p.i. by the appearance of microfilariae in the peripheral blood. A second transient depression occurred two weeks earlier against microfilarial antigen than it occurred against adult worm antigen. At 3 different times after the infection, the amount of adsorbed antibodies was assessed on adult worms and on microfilariae, which were isolated from blood and by a specially developed method from the internal organs. The percentual distribution of microfilariae in the different organs and blood changed during patency. In spleen, kidney, and lung a continuous increase was observed, whereas in heart and liver the percentage initially increased, and then decreased. The opposite course was seen in blood. Most antibodies adsorbed on the surface of microfilariae and adult worms belonged to the IgM class. Predominantly, the antibodies were detected on organ microfilariae, particularly on those in spleen and kidney, while blood microfilariae had lower amounts of bound antibodies. Furthermore, by complement fixation, no common antigens could be detected on the surface of host cells and the different L. carinii stages. PMID- 2907264 TI - The skin-dwelling microfilariae of Monanema martini in Lemniscomys striatus as potential drug screening model for onchocerciasis: midazolam effect in vitro. AB - The murid model of Monanema martini in Lemniscomys striatus was used to evaluate its potential as drug screening model in onchocerciasis. It had been described that the histopathology and the reaction to diethylcarbamazine treatment of this model closely resemble human onchocerciasis. To study further similarities the in vitro effect of midazolam was examined. Skin-dwelling microfilariae (mf) of M. martini were taken by skin snips and placed in either plain phosphat buffered saline or midazolam. Concentrations of 50 micrograms/ml midazolam significantly reduced motility within 15 min. The percentage of fully motile mf dropped to 9.2 and 1.4 after 15 and 30 min, respectively. In contrast to this finding fully motile mf were obtained after intraperitoneal injection of 60 mg/kg BW; but the technique used did not allow to evaluate the in vivo effect of midazolam. The similarities with the human disease and the finding that midazolam paralyses mf of M. martini like mf of O. volvulus in vitro indicate the potential of the model for simulating human onchocerciasis. PMID- 2907265 TI - [Vitamin A deficiency in a rural population of Mauritania and absence of a correlation with urinary schistosomiasis]. AB - This work is part of a wider study on urinary schistosomiasis in a West African rural population and was devoted to the assessment of vitamin A deficiency and the analysis of relations between serum retinol levels and Schistosoma haematobium infection. The study took place in two villages located in a southeastern region of Mauritania (Hodh-El-Gharbi), a semi-arid zone struck by the Sahel drought. During the dry season 1985, 206 children between 1 and 15 years of age were randomly selected (single-stage cluster sampling), 81 from the first village, and 125 from the second. The following information was recorded: sex, age (or age group), symptoms of vitamin A deficiency, weight for height (NCHS reference), S. haematobium eggs count, vitamin A level and anti schistosomiasis antibodies. In Kerkerat 4 children had eye signs of vitamin A deficiency and serum retinol concentration were found less than 100 micrograms/l in 8 subjects (10 +/- 3%) while 41 children had retinol serum concentration between 100 and 200 micrograms/l (50.6 +/- 5%). There was no difference between the age groups. In Limbehra most of children had serum retinol concentration greater than 200 micrograms/ml and no level less than 100 micrograms/l was found. In this village, children aged 10-15 years had a better retinol status than children under 10 years of age (chi 2 = 6.14, p less than 0.02). In both villages S. haematobium infection was not associated with a low serum retinol level. This study confirms that retinol deficiency is a public health problem in rural Mauritanian population, but keeping with other studies, there is no correlation with urinary schistosomiasis. PMID- 2907266 TI - Quantitation of antibodies to infective larvae in Wuchereria bancrofti filariasis. Short communications. PMID- 2907267 TI - Anaemia in bovine African trypanosomiasis. A review. PMID- 2907268 TI - Membranoproliferative glomerulonephritis in Takayasu's arteritis. AB - The occurrence of glomerulonephritis (GN) in patients with Takayasu's arteritis (TA) is rare. We describe a 28-year-old man with TA who presented with mesangial proliferative GN and subsequently developed membranoproliferative GN with nephrotic syndrome and deterioration of the renal function. The former is the most common type of GN complicating TA, while the latter has not been adequately reported in association with this disease. Although the mechanisms for the initiation and progression of these glomerular injuries are not clear, the present case suggests that a wider spectrum of GN can be seen in patients with TA and that cases of TA with urinary abnormalities should be followed carefully. PMID- 2907269 TI - Comparison of maxillofacial and dental injuries in four contact team sports: American football, bandy, basketball, and handball. AB - Maxillofacial and dental injuries were studied in registered players of American football, bandy, basketball, and handball in Finland between 1979 and 1985. In American football, where facial protection is complete and mandatory, maxillofacial and dental accidents accounted for only 1.4% of all accidents. In bandy, where facial protection was inadequate during the time of study (only the helmet and extraoral mouth protector were mandatory), the respective figure was 10.6%. The most frequent causes of injury were a blow from another player (in American football, basketball, and handball) or a blow from the stick (in bandy). In American football, the mean cost of treatment related to maxillofacial and dental injuries was only 60% of the mean total cost of all injuries. In contrast, the mean cost of treatment for maxillofacial and dental injuries in basketball and bandy was twice and three times as high, respectively, as that for all injuries. The need for adequate facial protection in contact sports is also discussed. PMID- 2907270 TI - Beyond hybridomas. Cell identification by in situ nucleic acid hybridization. AB - Nucleic acid hybridization is a powerful technique that has been developed almost entirely by molecular biologists. It has the potential to identify specific types of cells with far greater sensitivity and specificity than such current methods as polyclonal or monoclonal antibodies or lectins. As the RNAs or DNAs (probes) needed for this technique become available, it is likely to replace other methods of identifying many kinds of cells in tissue sections. PMID- 2907271 TI - [Continuous intrathecal opiate therapy with a portable drug pump in cancer pain]. AB - Terminal cancer patients report substantial pain frequently. Pain control can be achieved in many patients with conventional methods and analgesics. However, significant numbers of patients remain in pain. For these patients, continuous intrathecal narcotics delivered by an external portable pump via a subcutaneous port, offer substantially improved pain control with minimal risk of serious systemic complications. Duration of treatment in our 40 cancer patients lasted up to 11 month. Continuous intrathecal morphine or fentanyl relieved pain till death due to cancer. Supraspinal side effects of opioids were only seen during the first week of intrathecal narcotic treatment. No serious complications like meningitis or other infections were observed. Postmortem examination also could not detect changes of the cord or signs of arachnoiditis due to intrathecal narcotics or the implanted catheter. We conclude, that continuous intrathecal narcotic infusion by means of small portable pump is a very efficient method to control terminal cancer pain and enables treatment on an outpatient basis until death. PMID- 2907272 TI - Assessment of enzyme inhibition or stimulation in plasma membrane preparations. AB - The purity of isolated plasma membranes is routinely judged by the activity of enzymes present both in this membrane and other locations in the cell. However, since enzyme inhibition and/or stimulation often occurs following disruption of the cell, the question as to which enzyme(s) provides a reliable marker of membrane purity should be considered. We have devised a simple method with which to address this problem. Inhibition or stimulation of plasma membrane marker enzymes can be rapidly assessed in cell homogenates and subfractions by mixing both samples, with known enzyme activity, and observing any deviation from the expected combined activity. Should the activity remain constant that enzyme can be used to gauge the purity of the plasma membrane preparation. Of the four putative plasma membrane marker enzymes examined only one, gamma glutamyltranspeptidase appeared to give a reliable purity measurement in the cell system studied. PMID- 2907273 TI - Effects of an orally administered live Escherichia coli pilus vaccine on duration of lacteal immunity to enterotoxigenic Escherichia coli in swine. AB - Primigravid swine were vaccinated orally with a live enterotoxigenic Escherichia coli (ETEC) strain that produces pilus antigen K99. The titers of K99 antibody in colostrum and milk of vaccinates remained higher than those of nonvaccinated controls through the first lactation after vaccination (4 weeks). Some control swine had low titers of K99 antibody in colostrum or developed low titers of K99 antibody in milk during lactation. Lacteal K99 antibody titers of vaccinates dropped to control levels during the second lactation, 6 months after vaccination. Pigs suckling vaccinates and controls were equally susceptible to challenge exposure to K99+ ETEC during the second lactation. Orally vaccinated swine given a parenteral booster vaccination (with killed K99+ ETEC) during their second gestation had K99 antibody in milk through their second lactation. During the second lactation, these orally vaccinated parenterally revaccinated swine had higher titers of K99 antibody in postcolostral milk than did nonvaccinated controls, controls given only the parenteral booster injection, or controls vaccinated parenterally during both gestations. PMID- 2907274 TI - Antral bombesin: physiological regulator of gastrin secretion. PMID- 2907275 TI - Restriction fragment length polymorphisms in the mushrooms Agaricus brunnescens and Agaricus bitorquis. AB - Two Agaricus species, A. brunnescens (a commercial mushroom) and A. bitorquis (a wild, edible species), were examined for restriction fragment length polymorphisms. EcoRI-digested nuclear DNA from isolates of both species were cloned in plasmid vector pUC18. Ten random recombinant clones were used in Southern DNA-DNA hybridizations to probe EcoRI-digested DNA from 11 A. brunnescens isolates (7 commercial, 2 wild type, and 2 homokaryotic) and 7 A. bitorquis isolates. Most cloned fragments were polymorphic in both species. There were fewer different genotypes than expected, however, in the sample of commercial A. brunnescens strains. DNA from homokaryotic strains showed fewer bands in most hybridizations than DNA from heterokaryotic strains. All A. bitorquis isolates could be distinguished from each other as well as from every A. brunnescens strain. Putative homokaryons were detected by the loss of polymorphic bands among protoplast regenerates from one commercial strain and two strains collected in the wild. PMID- 2907276 TI - [Transmission of human malaria in a savanna village of South-West Burkina Faso]. PMID- 2907277 TI - The antimuscarinic activity of a dopamine receptor agonist (RDS-127) differentiates M2-muscarinic receptors of heart, ileum and trachea in guinea-pig. AB - The antimuscarinic action of a dopamine receptor agonist, 2-di-n-propylamino-4,7 dimethoxyindane (RDS-127) was evaluated using guinea-pig isolated electrically paced left atria, spontaneously beating atria, ileal longitudinal muscle and tracheal strip. RDS-127 competitively antagonized the responses to carbachol in all these tissues. RDS-127 exhibits higher selectivity for tracheal M2-muscarinic receptors than for cardiac and ileal receptors. In addition, the affinity of RDS 127 towards cardiac M2-muscarinic receptors was also greater than towards ileum. RDS-127 did not show any selectivity for M2-muscarinic receptors mediating negative inotropic and chronotropic effects. PMID- 2907278 TI - Staurosporine counteracts the phorbol ester-induced enhancement of neurotransmitter release in hippocampus. AB - The effects of staurosporine, introduced as a very potent inhibitor of protein kinase C (PKC), on evoked neurotransmitter release were investigated and compared with those of the other PKC inhibitors: 1-(5-isoquinolinesulfonyl)-2 methylpiperazine (H7) and polymyxin B (PMB). Slices of rabbit hippocampus, prelabelled with either [3H]noradrenaline, [3H]5-hydroxytryptamine or [3H]choline were superfused with physiological medium. During superfusion the slices were stimulated either electrically (3 Hz, 5 V/cm, 24 mA, 2 msec) or by high K+ (30 mM) for 2 min, respectively. Both the electrically and potassium evoked overflow were increased by the PKC activator 4 beta-phorbol 12,13-dibutyrate (PDB). The degree of the enhancement by PDB was dependent on the transmitter and the stimulation conditions used. These results may be explained by differences in the extent of activation of PKC during electrically or potassium evoked release. The PDB-induced enhancement of electrically or potassium evoked release of the 3 transmitters was counteracted by staurosporine (1 microM) in concentrations much lower than those required for H7 (100 microM) and PMB (100 microM). PMB, which has been shown to decrease electrically evoked transmitter release, similarly diminished K+-evoked release. In contrast, only the potassium evoked [3H]acetylcholine release was significantly diminished by staurosporine (1 microM) and H7 (100 microM). In conclusion, these results show again that facilitation of neurotransmitter release by phorbol esters is due to activation of PKC. PMID- 2907279 TI - Neuroleptic-like, anticonvulsant and antinociceptive effects of aporphine alkaloids: bulbocapnine, corytuberine, boldine and glaucine. AB - The aporphine alkaloids bulbocapnine, corytuberine, boldine and glaucine were studied in mice and compared with haloperidol, phenobarbital and morphine. All aporphines inhibited the exploratory rearing activity and elicited palpebral ptosis, catalepsy, hypothermia, and prolonged anesthesia by thiopental. They also reduced nociception (hot plate; phenylquinone-induced writhing) and (except for corytuberine) were anticonvulsant against harman and picrotoxin, but not against bicuculline and pentetrazol; corytuberine was proconvulsant. The aporphines (except for corytuberine) antagonized the apomorphine- and methylphenidate induced stereotyped gnawing and also the apomorphine-induced climbing activity; corytuberine was prostereotypic. The antignawing effects (including those of haloperidol) were stronger when the antagonists were administered after the agonists (gnawing full-fletched) rather than before them: this led to the speculation of a metaphilic interaction at central site(s). Clonazepam inhibited the antistereotypic effect (vs apomorphine) more potently with the aporphines than with haloperidol. The antinociceptive effect (writhing) of the aporphines was, in contrast to that of morphine, resistant to both naloxone and yohimbine. The latter applied also to the antilicking action in the hot plate test; the antijumping effect of boldine was (like that of morphine) antagonized by both yohimbine and naloxone, whereas that of corytuberine was inhibited only by naloxone and that of bulbocapnine preferentially by yohimbine. Hence, opioid and adrenergic mechanisms are unequally involved in the antinociceptive effects of the aporphines. The present results also showed that licking and jumping (in the hot plate test) are pharmacologically different phenomena. In low doses, the aporphines and haloperidol antagonized the antinociceptive effect of morphine (hot plate); hence, these drugs may be considered partial agonists or partial antagonists, respectively. PMID- 2907280 TI - In vitro effects of S.3341 on the spontaneous contractile activity of the rat portal vein: interference with the alpha-adrenergic stimulation. AB - The aim of this study was to evaluate the alpha 1-adrenoceptor properties of S.3341, a new alpha-adrenoceptor agonist. Experiments were performed by recording isometric tension of the rat portal vein. pD2 values and apparent intrinsic efficacy of alpha-adrenoceptor agonists (S.3341, norepinephrine, phenylephrine and clonidine) were assessed from cumulative concentration-response curves. Particular attention was paid to the variations in the amplitude of spontaneous contractions and the increase in the tonus of the vein induced by these agonists. The rank order of activity (pD2 values) of these agonists on the amplitude of spontaneous contractions and on the tonus was as follows: norepinephrine greater than or equal to phenylephrine greater than clonidine greater than S.3341. The activity of S.3341 on spontaneous contractions of the vein was found to be of the alpha 1-type only at concentrations higher than 10(-6)M. This concentration dependent effect was antagonized by prazosin but not by rauwolscine. For concentrations lower than 10(-6)M, S.3341 decreased the amplitude of spontaneous contractions. This effect was not modified by prazosin or rauwolscine and was affected (decreased) after treatment of the vein with 6-hydroxydopamine (6-OHDA). S.3341 was barely able to increase the tonus of the vein, whatever the concentration used. Moreover, S.3341 was able to antagonize the increase in amplitude of spontaneous contraction and tonus of the vein induced by clonidine and phenylephrine. The effect of S.3341 on the slow inward calcium current was also tested and no effect was found, even at high concentrations. The results suggest that in the rat portal vein, S.3341 is a weak partial alpha 1 adrenoceptor agonist which exhibits a quite novel property not related to an adrenergic stimulation or a calcium entry blocking property. The mechanism of this novel effect remains to be elucidated. PMID- 2907281 TI - Effects of beta-adrenergic agents on the regional cerebral blood flow in cortex and thalamus of the cat. AB - The effects of the beta-adrenergic agents isoprenaline, terbutaline, l,d propranolol, acebutolol, as well as d-propranolol, on the regional cerebral blood flow (rCBF) in cortex and thalamus and arterial blood pressure (ABP) were investigated following i.v. administration. The experiments were performed in 64 cats anaesthetized with ether and chloralose. The rCBF was measured using the thermistor thermoclearance technique. Isoprenaline, as well as terbutaline (1, 3, 5 micrograms/kg) decreased the cortical rCBF and the ABP (p less than .05). Both adrenergic agonists increased the thalamic rCBF despite the decrease in ABP (p less than .05). L,d-propranolol (1 mg/kg) abolished the effects of isoprenaline and terbutaline on thalamic rCBF. Acebutolol (0.6 mg/kg) or d-propranolol (0.5 mg/kg) did not alter isoprenaline- and terbutaline-induced effects on rCBF in thalamus. L,d-propranolol decreased the thalamic rCBF, whereas d-propranolol increased the rCBF in thalamus (p less than .05). Acebutolol did not change the thalamic rCBF significantly. The results obtained indicate that beta-adrenergic agents have heterogeneous effects on rCBF in cortex and thalamus. Their effects on thalamic rCBF seem to be accomplished by beta 2-adrenoceptor stimulation. PMID- 2907283 TI - Experimental aspects of transplantation of haemopoietic cells of fetal liver. AB - About 25% mice treated for radiation-induced bone marrow aplasia with allogeneic transplantation of histoincompatible fetal liver cells survived four months. The same survival time was observed in 80% of mice after transplantation of syngeneic fetal liver cells. Mice irradiated and not treated and those receiving transplants of allogeneic histoincompatible bone marrow died within a few weeks after transplantation. This observation confirms the reports on the therapeutic superiority of transplantation of haemopoietic fetal liver cells over transplantation of bone marrow of similar tissue incompatibility and reports on the usefulness of tissue matching, if possible. Another observation was an absence of inactivation of the haemopoietic stem cells in mixtures of genotypically different fetal liver cells. The animals receiving these cell mixtures showed survival rates similar to those of the animals receiving genetically homogenous cells. This opens theoretical possibilities for undertaking clinical trials of transplantation of cells from several fetal livers, especially in view of the accumulating reports that one human fetal liver may be too small to serve as a source of stem cells for ensuring successful transplantation. PMID- 2907282 TI - [Transient neonatal hyperthyrotropinemia]. AB - The systematic screening for congenital hypothyroidism allowed to better precise the transient abnormalities of thyroid function and to interpret their mechanisms and frequency. This study analysed the transient TSH increase observed in 74 children between 1982 and 1987. Eighteen children presented with an obvious disorder, most often iodine intoxication. In 31 cases, iodine poisoning, was likely, according to history. No precise etiology could be found in 25 cases. In 7 children, L-thyroxine treatment was necessary, for various durations. PMID- 2907284 TI - Synthesis of compounds with a possible Ca-antagonist and beta-blocking activity. PMID- 2907285 TI - [Protective effect of Sm 857 on allergen-induced immediate bronchoconstriction]. PMID- 2907286 TI - [Inhibitory effect of an alpha-2 adrenoceptor antagonist (midaglizole) on bronchial asthma--basic studies on experimental guinea pig bronchoconstriction]. PMID- 2907287 TI - Tardive dyskinesia clinic. PMID- 2907288 TI - Platelet serotonin uptake in panic disorder: comparison with normal controls and the effect of treatment. AB - Platelet serotonin uptake was measured in 59 patients with panic attacks and compared to 26 controls. Scatchard analysis of the data showed that the maximal rate of uptake (Vmax) of serotonin was significantly higher in patients than controls. The affinity constant (Km) was not different. In a sub-group of 24 patients, benzodiazepine treatment did not alter the kinetics of platelet serotonin uptake. These findings suggest an abnormality in serotonergic function in patients with panic attacks. Insofar as the platelet is a model of central neuronal function they support serotonergic hyperactivity as a biochemical basis of panic attacks. PMID- 2907289 TI - T cell regulated hematopoiesis--molecular interactions in hematopoietic control by CD2 and interleukin 2. AB - Studies are reviewed, which establish a novel regulatory role for the T cell surface molecule CD2 and the T cell lymphokine IL-2: Immunoregulation of hematopoiesis. IL-2 induces a receptor-specific inhibition of early erythroid progenitors. IL-2-induced inhibition of erythropoiesis is mediated by interferon gamma protein release and is associated with interferon-gamma mRNA accumulation. CD3-triggered p55 IL-2 receptor expression is a prerequisite for IL-2-induced erythropoietic inhibition and is associated with p55 mRNA synthesis. Hematopoietic effects of IL-2 are mediated by CD2/LFA-3 receptor ligand interactions. The studies demonstrate that the regulatory roles of IL-2 and CD2 extend beyond governance of the immune system itself and can subserve to control red cell production in vitro. PMID- 2907291 TI - Restriction-fragment-length-polymorphisms close to the human insulin gene on chromosome 11 and their possible relation to diabetes mellitus in a GDR population. AB - A polymorphic DNA sequence flanking the 5'-region of the human insulin gene was studied by means of Southern blot hybridization techniques in 92 diabetic and non diabetic individuals in order to investigate the possible relation of their allelic variants to certain types of diabetes. DNA was isolated from nucleated blood cells and digested with the restriction endonucleases EcoRI or Bg1 I. Only two classes of alleles were found (U and L). The small L-allele was predominantly found with the following frequency: 0.64 in controls, 0.795 in insulin-dependent diabetics, and 0.625 in non-dependent patients. It could be demonstrated that the L-allele and IDDM are associated. These data suggest that this allele seems to be a genetic marker for insulin-dependent diabetes mellitus. The putative function of the polymorphic region in the aetiology of diabetes mellitus and the possible genes being in linkage disequilibrium with it are not known so far. PMID- 2907290 TI - Molecular genetic studies in achondroplasia. PMID- 2907292 TI - Polymorphism of insulin gene area in Japanese: relationship with insulin dependent and non-insulin dependent diabetes. PMID- 2907293 TI - Genetic variants of the insulin receptor in type II (non-insulin dependent) diabetes mellitus. AB - DNA variation related to the insulin receptor gene was studied with the restriction endonucleases Sst 1 and Bgl II. These identified 4 alleles, termed S1 (5.3 kilobases), S2 (5.8 kilobases), B1 (23.4 kilobases) and B2 (20.0 kilobases). Random association between these two insulin receptor polymorphisms was found in all of the study groups. The frequencies of genotypes possessing the S2 allele in Caucasian controls (n = 54), race matched non-insulin dependent diabetics (n = 56) and insulin dependent diabetics (n = 34) were 0.06, 0.18 and 0.04 respectively (p less than 0.01 for NIDDM versus IDDM or controls by chi-squared test). There were no significant differences in frequencies of genotypes with the B1 or B2 alleles amongst these three groups. The S2 allele or adjacent loci may provide a useful genetic marker for NIDDM. PMID- 2907294 TI - Prostaglandin production by human promyelocytic leukemia (HL-60) cells. AB - A comparative analysis of prostaglandin production was carried out on human promyelocytic leukemia (HL-60) cells treated with either PMA or DMSO. When incubated with [1-14C]arachidonic acid these cells produced significant amounts of 6-keto prostaglandin F1 alpha, thromboxane B2, prostaglandin F2 alpha, prostaglandin E2, prostaglandin D2 and 12-hydroxy-5,8,10-heptadecatrienoic acid via the cyclooxygenase pathway. The major cyclooxygenase metabolite synthesized by these cells was prostaglandin F2 alpha. Its production increased significantly when the HL-60 cells were treated with PMA and decreased when treated with DMSO as compared to untreated control cells. This change in the production of prostaglandin F2 alpha appears to reflect alterations in cyclooxygenase activity. Another unidentified arachidonic acid metabolite was routinely observed in C18 high pressure liquid chromatography. The synthesis of this compound was inhibited by indomethacin. The unidentified metabolite was also seen in the human macrophage-like cell line U937. PMID- 2907295 TI - The carotid bodies of spontaneously hypertensive rats (SHR) after long-term stimulation by almitrine bismesylate. AB - The influence of daily oral application of 1.0 mg/kg almitrine bismesylate given from the 17th to the 30th week of age on the carotid bodies of male spontaneously hypertensive rats (SHR) was studied. Neither an enlargement nor histological changes of the carotid bodies were found. The results are compared with findings obtained after exposure of SHR to long-term hypobaric hypoxia and discussed. PMID- 2907296 TI - [Amino acid sequence of neurotoxins IV and V from the sea anemone Radianthus macrodactylus]. AB - Amino acid sequences of neurotoxins RTX-IV and RTX-V isolated from the sea anemone Radianthus macrodactylus were determined by the automated Edman degradation; their polypeptide chains consist of 48 and 47 amino acid residues, respectively. For identification of tryptophan-30 in toxin RTX-IV, its trypsin and chymotrypsin digests were investigated. Amino acid sequences of the above toxins show that they belong to a new structural class and that C-terminal positive charge and tyrosine-25 are important for toxic activity of sea anemone polypeptides. PMID- 2907297 TI - Absence of a close linkage between Alzheimer's disease susceptibility gene and a polymorphic DNA probe coding for beta-amyloid. AB - The hypothesis of a connection between Alzheimer's disease (AD) gene and the probe coding for beta-amyloid (beta-A), located on chromosome 21, was investigated in a large study group from Calabria, in which AD was transmitted as an autosomal dominant Mendelian trait. Segregation analysis of one EcoRI restriction polymorphism of beta-A, after molecular hybridization with a long cDNA probe of DNAs from key-individuals in the study group, determined that there was not a close connection between AD and beta-A. PMID- 2907298 TI - Somatostatin analogues in the treatment of the carcinoid syndrome. AB - Somatostatin analogs have been found useful in a variety of endocrine-related diseases. In particular, patients with malignant carcinoid syndrome benefit from their administration. A review of published data and a rationale for their use is hereby presented. PMID- 2907299 TI - Hypothalamic alpha-adrenergic blockade modifies drinking and blood pressure responses to central angiotensin II in conscious rats. AB - These experiments investigated in the awake rat the involvement of noradrenergic projections to the rostral hypothalamus in the drinking and pressor responses elicited by intracerebroventricular (i.c.v.) injections of 25 ng of angiotensin II. Phentolamine mesylate in doses of 2.5-125 micrograms injected into the rostral hypothalamus produced a dose-dependent depression of both the drinking and pressor responses elicited by i.c.v. administration of angiotensin II. A paradoxical increase in heart rate was associated with a decrease in pressor responses with increasing doses of phentolamine. This response was due to tissue injections, since pretreatment by injecting 12.5 micrograms of phentolamine into the ventricle did not block either the cardiovascular or drinking responses to i.c.v. injections of angiotensin II. Yohimbine (0.33-3.3 micrograms), DL propranolol (25 micrograms), and atenolol (25 micrograms) did not, but prazosin (0.7 microgram) did significantly alter the pressor responses. Although yohimbine also was without effect on drinking, prazosin reduced the drinking responses. These results suggest that alpha 1-adrenergic receptors in the rostral hypothalamus are involved in the control of both the drinking and pressor responses elicited by i.c.v. injections of angiotensin II. In the case of propranolol and atenolol, beta-adrenergic receptors altered only the drinking response in a nonspecific manner by eliciting competing behaviors. Whether they are involved in modifying the drinking response only remains to be demonstrated. PMID- 2907300 TI - In vivo interactions between prejunctional alpha 2- and beta 2-adrenoceptors at the level of the adrenal medulla. AB - The combined effect of a beta 2-antagonist and an alpha 2-agonist on the release of adrenal catecholamines was studied in the anaesthetized and vagotomized dog. The electrical stimulation of the splanchnic nerve (5-V pulses of 2 ms duration for 3 min at a frequency of 3 Hz) produced a significant rise in adrenal catecholamine release in the adrenal vein. Intravenous injection of a beta 2 antagonist significantly reduced this response and a subsequent injection of an alpha 2-agonist further reduced the release of catecholamines. However, if the alpha 2-agonist is injected first, the release is not different compared with the control stimulation, and the subsequent injection of the beta 2-antagonist also did not modify the release in response to electrical stimulation. These results suggest that the blockade of presynaptic beta 2-receptors reduces the release of adrenal catecholamines without interfering with the activation of the alpha 2 adrenoceptors. In contrast, the pretreatment with the alpha 2-agonist, which does not modify the release of catecholamine at 3 Hz, seems to interfere with the inhibitory effect of the beta 2-antagonist. PMID- 2907301 TI - Radiographic evaluation of foot and ankle injuries in the athlete. AB - Injuries of the ankle and foot in athletes are quite common. They range from the extremely simple sprain to the difficult stress fracture, and may result in long term disability. In all cases, the athlete is best treated after an accurate diagnosis is achieved. PMID- 2907302 TI - Effect of phospholipase A2 and cholesterol oxidase on perazine and promethazine penetration into human erythrocytes and on fluidity of the membrane. PMID- 2907303 TI - Conformational study of a histamine H2-receptor antagonist: crystal structures of 2-acetoxy-N-[3-[m-(1-piperidinomethyl)phenoxy]propyl]acetamide (roxatidine acetate) and its hydrochloride salt. PMID- 2907304 TI - Marine terpenes and terpenoids. V. Oxidation of sarcophytol A, a potent anti tumor-promoter from the soft coral Sarcophyton glaucum. PMID- 2907305 TI - Bioactive marine diterpenoids from Japanese soft coral of Clavularia sp. PMID- 2907306 TI - Synthesis and histamine H2-antagonist activity of 4-quinazolinone derivatives. PMID- 2907307 TI - Effects of ketanserin and 3-[2-[4-(o-methoxyphenyl)-1-piperazinyl]ethyl] 2,4(1H,3H)- quinazolinedione monohydrochloride (SGB-1534), anti-hypertensive agents, on 3H-serotonin and 3H-ketanserin bindings to serotonergic (5HT1 and 5HT2) receptors in dog brain and aorta. PMID- 2907308 TI - [2 cases of type II tyrosinosis (Richner-Hanhart syndrome)]. PMID- 2907309 TI - [Uveal reaction in an asthmatic patient treated by a local beta-blocker]. PMID- 2907310 TI - Effects of somatostatin immunoneutralization on growth and endocrine parameters in chickens. AB - The effects of somatostatin immunoneutralization on growth rate, growth hormone (GH) secretion and circulating insulin-like growth factor I (IGF-I) concentrations were investigated in chickens through the use of passive and active immunization techniques. Intravenous bolus injection of goat antisomatostatin stimulated a significant (P less than .05) increase in plasma GH levels for one hour post-injection in four and six week old male broiler chickens. The GH response to an intravenous bolus injection of hGRF44NH2 was similar in the antisomatostatin treated chicks and normal goat serum treated controls. Despite the presence of circulating somatostatin antisera after 28 hours, plasma GH levels were not different between control and antisomatostatin treated chicks at that time. Continuous administration of somatostatin antisera by Alzet pump over a two-week period resulted in significant (P less than .05) elevations in plasma GH levels at one week post-implantation and in circulating IGF-I concentrations after two weeks of administration. Chicks which developed antibodies against somatostatin following active immunization exhibited a 7.1% increase in growth rate which was associated with a significant decrease in abdominal fat. However, neither GH nor IGF-I concentrations were elevated in the chicks which developed somatostatin antibodies. Thus, the benefits gained from somatostatin immunoneutralization may be exerted through mechanisms other than GH. PMID- 2907311 TI - Synergism and diurnal variations of human growth hormone-releasing factor (1 29)NH2 and thyrotropin-releasing factor on growth hormone release in dairy calves. AB - Sixteen male Holstein calves averaging 168 kg body weight (BW) were used to determine the effects of human growth hormone-releasing factor (1-29)NH2 (hGRF (1 29)NH2; .22 micrograms/kg BW), thyrotropin-releasing factor (TRF; .165 micrograms/kg BW) or hGRF (1-29)NH2 plus TRF (.22 and .165 micrograms/kg BW, respectively) on growth hormone (GH) release in animals exposed to 16 hr of light (L): 8 hr of dark (D) (lights on at 0100 hr) and hGRF plus TRF (.22 and .165 micrograms/kg BW, respectively) in animals exposed to 8L:16D (lights on at 0900 hr). For each treatment, times of iv injection were 0400, 1000, 1600 and 2200 hr. In animals exposed to 16L:8D, average GH peaks reached after hGRF (1-29)NH2 or TRF injections were 49.7 and 32.0 ng/ml while the area under the GH response curve (AUC) were 1247 and 1019 ng/ml.min, respectively. There was no significant effect of times of injection on GH release following the separate injection of hGRF(1-29)NH2 or TRF. In animals exposed to 16L:8D, GH peaks and AUC after hGRF plus TRF injections were 226.4, 189.2 and 116.8 ng/ml, and 4340, 3660 and 2415 ng/ml.min at 0400, 1000 and 1600 hr (lights on), respectively but only 42.3 ng/ml and 1692 ng/ml.min at 2200 hr (lights off). In animals exposed to 8L:16D, GH levels and AUC after hGRF plus TRF injections reached 177.5 and 180.5 ng/ml, and 2759 and 3704 ng/ml.min at 1000 and 1600 hr (lights on) but only 84.0 and 72.7 ng/ml, and 1544 and 1501 ng/ml.min at 0400 and 2200 hr (lights off), respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2907312 TI - Modulation of growth hormone-releasing factor-induced release of growth hormone from bovine pituitary cells. AB - Growth hormone (GH)-releasing factor (GRF) at concentrations of 10(-12) through 10(-7) M for 6 hr linearly increased GH release (b1 = 10.4 +/- .3) from bovine anterior pituitary cells in culture. Maximum release of GH (262% above controls) occurred at 10(-7) M GRF. In contrast, GH release-inhibiting factor (SRIF) at 10( 12) through 10(-5) M had no effect on basal concentrations of GH. In a second experiment, as the proportion of SRIF relative to GRF increased, SRIF suppression of GRF-induced GH release from anterior pituitary cells increased. In a third experiment, anterior pituitary cells cultured in media containing fetal calf serum (FCS) were treated with cortisol (0 or 10 ng/ml media) for 24 hr before exposure to 10(-13) through 10(-7) M GRF. GRF linearly increased GH secretion (b1 = 7.4 +/- .3) and cortisol augmented this response (b1 = 10.5 +/- .6). However, when cells were cultured in media containing dextran-charcoal treated FCS, cortisol did not alter GRF-induced GH release. Our results demonstrate that GH response of bovine anterior pituitary cells to GRF was modulated negatively by SRIF. However, augmentation of GRF-induced GH release by cortisol was evident only when cells were cultured in media supplemented with untreated FCS. PMID- 2907313 TI - Influence of age and sex on basal secretion of growth hormone (GH) and on GH induced release by porcine GH-releasing factor pGRF(1-29NH2) in growing pigs. AB - The aim of this study was to determine the effect of age and sex on basal secretory patterns of growth hormone (GH) and growth hormone-releasing factor (GRF) induced GH release. Eighteen pigs (9 castrated males and 9 females) were stimulated with pGRF(1-29)NH2 at 7,11,15,19 and 23 weeks of age. Blood samples were taken from each animal via jugular vein cannulae every 20 min, from 6 hr before to 5 hr after iv GRF administration at a dose of 4 micrograms/kg. GH baseline levels, amplitude of the GH peaks, area under the GH peaks and the overall mean of GH serum levels decreased (P less than .001) with age in both sexes. Age also had a marked effect on GRF-induced GH release: the amplitude of GH peaks and area under the GH peaks decreased (P less than .001) with age. The GH response to pGRF(1-29)NH2 varied considerably, depending on the timing of the episodic endogenous secretion of GH. An immediate response (less than 30 min) was observed when GRF was injected at the end of a trough period or at the beginning of a peak, but there was no immediate response when GRF was injected at the end of a peak or at the beginning of a trough period. Our results show that both endogenous GH secretion and pGRF(1-29)NH2-induced GH release declines with age, suggesting a decreased sensitivity of the somatotroph cells to GRF with age; and that the high variability of the GH response to pGRF(1-29)NH2 stimulation depends greatly on the timing of the episodic endogenous GH release, thus implying a possible episodic endogenous somatostatin secretion by the hypothalamus. PMID- 2907314 TI - Suxamethonium-induced facilitation of spontaneous frontal EMG activity. AB - The behaviour of spontaneous frontal electromyographic activity (FEMG) was studied during the recovery from suxamethonium and vecuronium block. In order to obtain comparable conditions in the study groups, the duration of the suxamethonium block was prolonged with a suxamethonium infusion. The FEMG was continuously recorded and the evoked electromyographic (EEMG) and twitch tension (ETT) responses were measured every 10 s from the thenar muscles. The median FEMG remained at the base level in 8 of the 12 vecuronium patients, despite a 50% recovery of EEMG. In the suxamethonium group there was an increase in FEMG in all six patients when EEMG had recovered to 10%, and significantly higher FEMG readings were obtained during further recovery from the block. Thus, early recovery of neuromuscular transmission is detected by FEMG more easily when suxamethonium is used instead of vecuronium. The different behaviour of FEMG may reflect a difference in the recovery ratio of ETT/EEMG or in the anaesthetic depth caused by the two types of neuromuscular blockers. PMID- 2907315 TI - A double-blind comparison between nitrazepam, lorazepam, lormetazepam and placebo as preoperative night sedatives. AB - Benzodiazepines are used as hypnotics to reduce anxiety and give a good night's sleep on the night prior to surgery. In a double-blind procedure, patients were given either lorazepam (2 mg or 4 mg), lormetazepam (1 mg or 2 mg), nitrazepam 10 mg or placebo. Measures were taken of sleep, anxiety, memory and after-effects. There was no evidence that the drugs reduced anxiety, nor evidence of amnesia. Quality and length of sleep was shown to be better for nitrazepam (P less than 0.05), lorazepam 2 mg (P less than 0.05) and lorazepam 4 mg (P less than 0.01), compared with placebo. However, significantly higher ratings of clumsiness and confusion as after-effects were found with nitrazepam (P less than 0.05), and clumsiness (P less than 0.005), slurred speech and blurred vision (P less than 0.01), sleepiness, nausea, weakness and confusion (P less than 0.05) with lorazepam 4 mg. It was concluded that lorazepam 2 mg produced the greatest net benefit. PMID- 2907316 TI - Priming with atracurium and vecuronium. PMID- 2907317 TI - [Dapiprazole in the treatment of drug withdrawal symptoms]. PMID- 2907318 TI - Trans-racial studies implicate HLA-DQ as a component of genetic susceptibility to type 1 (insulin-dependent) diabetes. AB - Type 1 (insulin-dependent) diabetic patients and control subjects of Afro Caribbean Negroid racial origin were investigated by serological HLA-DR-typing and restriction fragment length polymorphism analysis using DNA probes corresponding to the DQ alpha, DQ beta and DR beta chain genes. Combined analysis indicated that four DR antigens are positively associated with the condition in Negroid subjects - DR3, 4, 7 and w9. DR3 and 4 are also associated in Caucasians, but the relative risk for DR3 is lower in Negroid subjects. The DR7 association is specific for the Negroid race, and DRw9 is only weakly associated in Caucasoid subjects. Restriction fragment length polymorphism analysis demonstrated a DQ beta restriction pattern in Negroid subjects which is absent from Caucasoid subjects. This pattern was associated with DRw9 and a subset of DR7, and was markedly increased in frequency in diabetic patients compared with control subjects (48.7% vs 10.4%, respectively; p less than 10(-4). In the absence of this pattern, DR7 showed no positive association. DR3 in Negroid subjects was associated with two distinct DQ alpha-DQ beta patterns, only one of which was positively associated with diabetes. A DQ beta pattern, in linkage disequilibrium with different DR antigens in different races, conferred a consistent protective effect against the development of Type 1 diabetes. Trans-racial genetic analysis thus supports a primary role for DQ in susceptibility to Type 1 diabetes. PMID- 2907319 TI - Two distinct HLA-DR3 haplotypes are associated with age related heterogeneity in type 1 (insulin-dependent) diabetes. AB - Heterogeneity between two haplotypes in linkage disequilibrium with DR3: B8, C4AQOB1,BfS,DR3 and B18,C4A3BQO,BfF1,DR3, with regard to age at onset of Type 1 (insulin-dependent) diabetes mellitus, was investigated in 325 unrelated French patients (146 males and 179 females, age at onset 1 month to 29 years) who were genotyped for HLA-A, B, C, DR and Bf and 225 of whom were typed for the C4A, B complement components. A subgroup of 82 patients and 75 control subjects were tested for DR beta and DQ beta DNA restriction fragment length polymorphism. The distribution according to age at onset and the mean ages at onset were compared between patients bearing B8, DR3 (n = 58), B18,DR3 (n = 62) or other DR3 haplotypes (Bx, DR3, n = 70), the haplotype segments C4AQOB1,DR3 (n = 41) or C4A3BQO,DR3 (n = 52) and the C4 null alleles C4AQO (N = 48) or C4BQO (n = 112) alone. The B8,DR3 haplotype, its smaller segment C4AQOB1,DR3 or C4AQO alone were associated with age at onset after 6 years (p less than 0.01, less than 0.08 and less than 0.02 respectively); on the other hand, the B18,DR3 haplotype, its segment C4A3BQO,DR3 or C4BQO alone were significantly more frequent in patients aged less than 6 years at onset (p less than 0.02, less than 0.01 and less than 0.01 respectively). Accordingly, the mean age of onset was significantly lower in the latter compared with the former patients (p less than 0.02, less than 0.02 and less than 0.01 respectively). No age-related variation was observed in BX,DR3 patients and their mean age of onset was intermediate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2907320 TI - Expression patterns of the homeo box-containing genes En-1 and En-2 and the proto oncogene int-1 diverge during mouse development. AB - We have compared the expression of the murine genes En-1,En-2, and in-1 during development by in situ hybridization. Expression of all three genes was first detected at 8.0 days in overlapping bands of the anterior neural folds. By 12.0 days the expression patterns diverged. En-1 and En-2 were expressed in a similar ring of cells in the central nervous system (CNS) at the midbrain/hindbrain junction. En-1 was also expressed de novo in two lateral stripes extending the length of the hindbrain and spinal cord, in the developing vertebral column, in two lateral stripes of dermatome-derived cells, and in the tail and limb buds. By 12.0 days int-1 expression showed little overlap with the En genes and could not be detected at later stages. At 15.5 days En gene expression was primarily limited to the midbrain/hindbrain in overlapping but nonidentical sets of differentiated cells. In the adult, En-1 and En-2 marked the same sets of cells in the pons, but En-2 alone was detected in the granular layer of the cerebellum. The results are consistent with int-1 and the En genes playing a role early in development in defining spatial domains in the CNS. Later in development the En genes may have an additional function in neurogenesis. En-1 expression in the developing pericordal tube suggests that it may also be involved in vertebral assembly. PMID- 2907321 TI - Molecular analysis of even-skipped mutants in Drosophila development. AB - The homeo box gene even-skipped (eve) plays a key role in the regulation of the Drosophila segmentation pattern. eve- embryos lack segment borders and show altered activities of several segmentation genes, including fushi tarazu (ftz), engrailed (en), and wingless (wg). Here, we present evidence that eve influences its own expression in a tissue-specific manner. Each of four different eve mutations disrupts the normal eve expression pattern, and null mutations cause a premature loss of eve products in ectodermal, but not mesodermal, tissues. Molecular characterization of eve mutations indicates that disruptions of the eve pattern are not due to alterations in the eve promoter but, instead, involve abnormal eve proteins. Two different eve mutations cause single amino acid substitutions within the homeo box, and we discuss the implications of these changes with regard to homeo box gene function. We also present evidence that eve+ gene activity is not only required for the activation of the odd-numbered en stripes but also for the correct positioning of each ftz stripe. We present a model for the loss of en expression in eve- embryos, based on the concentration dependent regulation of the ftz pattern by eve+ products. PMID- 2907322 TI - Isolation and expression of cDNA clones coding for two sequence variants of Xenopus laevis histone H5. AB - We have cloned and characterized cDNAs coding for two variants of Xenopus laevis H5 histone protein (previously called H1s). cDNA was synthesized from RNA of immature erythrocytes in a single reaction using a modification of the method of Gubler and Hoffman [Gene 25 (1983) 263-269], and blunt-end ligated into the HincII site of the phage vector M13mp9. Immunological screening with a polyclonal antibody yielded two clones expressing H5 peptide. Sequence characterization revealed that both clones contained partial cDNA inserts and that the smaller 340 bp clone initiated reverse transcription within the coding region, at a site rich in adenine. Rescreening of the cDNA bank by nucleic acid hybridization produced eleven additional H5 clones, one of which coded for a second variant of H5. These two variants, called XLH5A and XLH5B, are very similar in sequence and code for proteins of 195 and 193 amino acids, respectively, which may be the H1D and H1E variants observed previously. XLH5, avian H5 and human H1O share identity at both nucleotide and amino-acid sequence levels. Further, the XLH5-coding mRNA is likely polyadenylated and lacks the highly conserved, 23-nucleotide dyad symmetry element found within the 3' untranslated regions of most histone-coding mRNAs. PMID- 2907323 TI - A family of high-copy-number plasmid vectors with single end-label sites for rapid nucleotide sequencing. AB - A set of plasmid vectors was developed which allows fast sequencing by the chemical degradation method. These high-copy-number vectors are derivatives of the plasmid pUC8 containing different multiple-purpose cloning sites flanked by unique recognition sequences for the restriction enzymes BstEII, Tth111I and Eco81I as sites for end-labelling DNA. Due to their partially asymmetric recognition sequences, each of these three restriction sites can be singly end labelled by a filling-in reaction with selected nucleotides. This allows easy single end-labelling of any cloned DNA fragment for sequencing by the chemical degradation method without any isolation and purification step after the labelling reaction. In addition, the nucleotide sequence of the complementary strand from the same end can be determined by the dideoxy chain termination procedure using the universal M13 primers. In most of the new vectors, the reading frame of the lacZ' gene is retained, allowing identification of cloned fragments. PMID- 2907325 TI - Effect of iron on adhesion of urinary Escherichia coli. PMID- 2907324 TI - Liquid membrane phenomenon in the biological actions of gonadal steroid hormones. PMID- 2907326 TI - Ultracytochemical localization of adenylate cyclase and guanylate cyclase in crushed peripheral nerves. AB - Cellular and subcellular distribution of adenylate cyclase (AC) and guanylate cyclase (GC) activities in crushed peripheral nerves during regeneration were studied at the electron microscope level. In unlesioned nerves, no AC reaction product could be evidenced, whereas GC was detectable on the plasma membranes of Schwann cells, myelinated and nonmyelinated fibers, and within nonmyelinated axons. At 24 hours after the crush, AC reaction product was found within axonal segments proximal to the zone of the crush in association with mitochondria. At this stage, macrophage-like cells, which probably are transformed Schwann cells, polymorphonuclear leucocytes, and endothelial cells displaying an intense AC reaction product could be detected. On the other hand, at 24 hours after the crush, GC was no longer detectable, except on occasional unlesioned nerve fibers. At 48 hours after the lesion, AC reaction product was no longer detectable within axons, and all AC positivity was associated with plasma membranes of non-neuronal cells, including transformed Schwann cells, occasional macrophages, polymorphonuclear leucocytes, fibroblasts, and elongated cells. As to GC, images similar to those obtained at 24 hours were observed until 48 hours after the crush. From the 7th to the 28th postlesion day, AC activity was localized exclusively to the plasma membranes of fibroblasts and elongated cells. Transformed Schwann cells were no longer detectable, whereas normal Schwann cells and regenerating axons could be seen, and these showed no AC reaction product in analogy to the absence of AC reaction product of unlesioned nerves. During the same period, GC again was detectable on regenerating fibers with the same subcellular localization as that of unlesioned nerves. The present results strongly suggest that starting from the second postcrush day, cells invading the lesioned zone and transformed Schwann cells, all taking part in the formation of the new perineurial tissue, display a high AC activity, which should be taken into account when measuring cyclic adenosine monophosphate (cAMP) levels under these conditions. Also, our data suggest that GC is involved primarily in regeneration processes that occur in crushed peripheral nerves. Thus, the pattern of AC distribution in peripheral unlesioned and lesioned nerves appears to be exactly the opposite of the GC localization examined under similar experimental conditions insofar as nervous fibers are concerned. PMID- 2907327 TI - Influence of arachidonate metabolism on enhancement of intracellular transglutaminase activity in mouse peritoneal macrophages. AB - We examined whether arachidonate metabolism exerted any influence on the enhancement of intracellular transglutaminase activity in mouse peritoneal macrophages. Enhancement of the intracellular transglutaminase activity was observed on stimulation of macrophages with normal sheep red blood cells (SRBC) or immunoglobulin G (IgG)-coated SRBC, and was inhibited by inhibitors of phospholipase A2 and cyclooxygenase. Moreover, prostaglandin E2 (PGE2), a main product of the cyclooxygenase pathway, leukotriene B4 (LTB4), a product of 5 lipoxygenase, and arachidonic acid also could directly induce high levels of intracellular transglutaminase activity without stimulation of macrophages by SRBC or IgG-coated SRBC, but leukotriene C4, prostaglandin D2, and prostacyclin were unable to induce high activity of the enzyme. Enhancement of transglutaminase activity induced by LTB4 was inhibited by cyclooxygenase inhibitor, but the enzyme activity induce by PGE2 was not inhibited. Furthermore, the quantity of PGE2 released into the culture medium of macrophages stimulated with SRBC or IgG-coated SRBC correlated well with the activity of intracellular transglutaminase in macrophages. Moreover, enhancement of transglutaminase activity by treatment of macrophages with SRBC or IgG-coated SRBC was partially suppressed by sodium benzoate, which is a scavenger of hydroxy radical. These findings suggest that arachidonate metabolism, in particular the cyclooxygenase pathway, plays an important role in the enhancement of intracellular transglutaminase activity. PMID- 2907328 TI - Purification and characterization of chicken liver cathepsin B. AB - Cathepsin B was purified, 400-fold, to homogeneity from chicken liver. The enzyme comprised a mixture of two kinetically indistinguishable forms (approximately 1:1), which were separated on concanavalin A (Con A)-Sepharose; one consisting of Mr 25,500 and 5,000 polypeptide chains bound to Con A-Sepharose but the other, composed of Mr 24,500 and 5,000 polypeptide chains, did not. N-terminal amino acid sequence analyses of a mixture of the Mr 25,500 and 24,500 polypeptide chains, and of the Mr 5,000 polypeptide chain revealed single amino acid sequences, respectively. These amino acid sequences were homologous to those of the heavy and light chains of mammalian enzymes, respectively. The chicken liver and mammalian cathepsin B were similar in structure and properties. PMID- 2907329 TI - Molecular cloning and expression of a gene for a factor which stabilizes formation of inhibitor-mitochondrial ATPase complex from Saccharomyces cerevisiae. AB - Stabilizing factor, a 9 kDa protein, stabilizes and facilitates formation of the complex between mitochondrial ATP synthase and its intrinsic inhibitor protein. A clone containing the gene encoding the 9 kDa protein was selected from a yeast genomic library to determine the structure of its precursor protein. As deduced from the nucleotide sequence, the precursor of the yeast 9 kDa stabilizing factor contains 86 amino acid residues and has a molecular weight of 10,062. From the predicted sequence we infer that the stabilizing factor precursor contains a presequence of 23 amino acid residues at its amino terminus. We also used S1 mapping to determine the initiation site of transcription under glucose-repressed or derepressed conditions. These experiments suggest that transcription of this gene starts at three different sites and that only one of them is not affected by the presence of glucose. PMID- 2907330 TI - Listeriosis: new problems with an old pathogen. PMID- 2907331 TI - Surveillance cultures in the neutropenic patient. PMID- 2907332 TI - Microbiological investigation of an outbreak of bacteraemia due to Streptococcus faecalis in an intensive care unit. AB - An increased incidence of bacteraemia due to Streptococcus faecalis in a Critical Care and Trauma Centre (CCTC) during November 1985 prompted investigation. During the epidemic 21 blood cultures from five CCTC patients were positive for S. faecalis. A point prevalence culture survey revealed two more strains from wounds from two of these five patients. Fifteen strains from blood cultures and the two strains from wound sites were further characterized by conventional biotyping methods and susceptibility patterns, but they could not be differentiated from 40 unrelated control strains by these methods. The API-20S and the API-ZYM systems, however, were able to distinguish the outbreak isolates from the control strains. This investigation supports the hypothesis that S. faecalis is capable of causing cross-infection, and it may be necessary to characterize enterococci beyond routine tests to identify an outbreak due to this organism. PMID- 2907333 TI - A study of the value of electrophoretic and other techniques for typing Acinetobacter calcoaceticus. AB - Forty-four isolates of Acinetobacter calcoaceticus var anitratus collected during hospital outbreaks were studied using polyacrylamide gel electrophoresis (PAGE), plasmid analysis, antibiograms and biochemical tests to determine their degree of similarity. Reproducibility tests were also carried out on the PAGE and biochemical techniques to determine their validity when used to compare bacteria of the same type isolated intermittently. PAGE data was analysed densitometrically and isolates compared using a similarity matrix. All methods were able to subdivide the isolates, but results did not always correlate well between methods. Reproducibility data indicated that careful attention to technique is required when organisms are examined by PAGE sequentially. Results suggest that no single biotyping technique is likely to be adequate and that electrophoretic, biochemical and antibiogram data may complement one another and other epidemiological data in the typing of these organisms. PMID- 2907334 TI - Monitoring the bacteriological quality of potable waters in hospital. AB - We report a survey of the bacteriological quality of potable waters from hospitals. In the 12-month period February 1986 to January 1987, 646 samples were examined from 25 hospitals. Coliforms were isolated from eight (1.2%) samples, received from three hospitals. These hospitals did not, therefore, satisfy the European Community (EC) directive on potable water quality. Three hundred and four (47%) samples had total viable counts higher than the guidelines given in the EC directive on potable waters. Thirteen (52%) of hospitals surveyed submitted at least one unsatisfactory sample and six (24%) submitted more than 50% unsatisfactory samples. Water quality was generally poorer in the summer and autumn. Estimation of the total viable count is an inexpensive and simple method for monitoring the microbial quality of hospital waters. PMID- 2907335 TI - The laboratory interpretation of coagulase-negative staphylococcal bacteraemia in neonates. AB - In an attempt to detect markers of significance of coagulase-negative staphylococci (CNS) isolated from neonatal blood cultures, epidemiological data and the rate of appearance of positive blood cultures were examined. The main epidemiological factor studied was the relative abundance of the different biotypes of CNS in blood cultures, on neonatal skin and the hands of neonatal unit staff. Our results showed that the relative recovery rates of biotypes found from these sources showed no significant differences. The number of positive blood culture bottles in each set and the number of days taken for growth to appear showed wide variations. A higher proportion of aminoglycoside-resistant strains were found in the group showing both blood culture bottles positive and in the group where isolates were obtained by 24 h of incubation. We conclude that there is no advantage in biotyping CNS in assessing clinical significance, but the association of aminoglycoside resistance with the isolation pattern of CNS in neonatal blood cultures requires further examination. PMID- 2907336 TI - Needlestick injuries: how can we teach people better about risk assessment? AB - At work people run some small risk of death or injury which is directly attributable to their occupation. In biomedical sciences the accidental puncture of the skin by hypodermic needles, other instruments or broken glass has long been regarded as an occupational hazard and there is increasing concern that staff could become infected with a range of micro-organisms, including hepatitis B and the Human Immunodeficiency Virus (HIV). Needlestick injuries should be preventable if staff are trained effectively and take care about disposal of used syringes and needles. Staff at risk must be offered pre-exposure vaccination for hepatitis B and resources must be provided for special training. Fundamental changes may be required in methods and equipment and a number of new ways of targeting groups of health care staff with information are discussed. PMID- 2907337 TI - Why do people fail to observe safety precautions in high risk situations? PMID- 2907338 TI - Needlestick injuries: mechanisms and control. AB - Consideration of a linear model for venepuncture and patterns that emerge from the literature can help to understand the occurrence of occupational needlestick injuries which are common in healthcare workers. A systematic approach can also help in evaluation of potential control measures and in cost-benefit analysis. PMID- 2907339 TI - A method of audit for ward clinical waste. AB - We describe the conduct of an annual audit concerning the handling of clinical waste at ward level. The annual audit resulted in an improvement in the supply of colour coded bags and holders, and improved the efficiency of waste disposal in the hospital. The annual report of the audit enabled the hospital administrators to pinpoint defects and was partly responsible for the appointment of an "administrative officer responsible for waste". PMID- 2907340 TI - Hand scrubbing system in theatres and bacterial contamination. PMID- 2907341 TI - Microbiological evaluation of a hospital-delivered meals service using precooked chilled foods. PMID- 2907342 TI - The role of antiseptics in the management of patients with long-term indwelling catheters. PMID- 2907343 TI - Cell mediated immunity in sarcoidosis. PMID- 2907344 TI - Anti-anginal drugs: calcium channel blockers, beta-adrenergic blockers and nitrates. PMID- 2907345 TI - The role of laparoscopy in management of nonpalpable testes. AB - Laparoscopy is the ideal first operative step in management of boys with nonpalpable testes. No other investigation is as reliable in locating a nonpalpable testis or in confirming its absence. Whatever the laparoscopic findings, further operative intervention is generally necessary and the laparoscopic findings determine the subsequent operative steps. Laparoscopy also permits endoscopic manipulation such as application of a spermatic vessel clip for staged Fowler-Stephens orchidopexy. Herein we report our experiences with laparoscopy in 30 patients with nonpalpable testes. PMID- 2907346 TI - Simulating the time-course of clinical paralysis. AB - This computer program depicts the concentration-time curves for the nondepolarizing neuromuscular blocking agents. It simulates their administration by single and multiple iv injections, and with continuous infusion, alone and in combination. It provides the plasma concentrations related to 75% and 25% depression of the twitch response, using these to calculate clinically useful pharmacodynamic values, such as the duration of surgical relaxation, and the recovery index. These simulations allow the user to contrast the time-course of relaxation to be expected with various dosage regimens. PMID- 2907347 TI - Molecular cloning of cDNA for the rat F1-ATPase beta subunit. PMID- 2907348 TI - Chronic beta-adrenoceptor antagonist treatment modulates human cardiac and vascular beta-adrenoceptor density in a subtype-selective fashion. AB - In order to study the regulation of human cardiac and vascular beta-adrenoceptors as induced by beta-adrenoceptor antagonism we determined beta-adrenoceptor density and subtype distribution in right atria, saphenous veins and lymphocytes from 60 patients undergoing coronary artery bypass grafting; 42 of these patients were chronically treated with different beta-adrenoceptor antagonists [without intrinsic sympathomimetic activity: propranolol, sotalol (non-selective); metoprolol, atenolol (beta 1-selective); with intrinsic sympathomimetic activity: pindolol (non-selective)] and 18 patients not treated with beta-adrenoceptor antagonists were taken as controls. In the right atria (70% beta 1-, 30% beta 2 adrenoceptors) of all groups except the pindolol group, total beta-adrenoceptor density was higher than in controls. A more detailed analysis revealed that all beta-adrenoceptor antagonists increased right atrial beta 1-adrenoceptor density, but right atrial beta 2-adrenoceptor density was increased only in the sotalol/propranolol group, remaining unchanged in the metoprolol and atenolol groups, and was decreased in the pindolol group. Similarly, in saphenous veins and circulating lymphocytes (in both, the beta-adrenoceptors were almost exclusively beta 2-adrenoceptors), only propranolol/sotalol increased the beta 2 adrenoceptor density, while metoprolol or atenolol did not affect it. Moreover, in the pindolol group lymphocyte beta 2-adrenoceptor density was decreased. It is concluded that in man all beta-adrenoceptor antagonists without intrinsic sympathomimetic activity increase cardiac and vascular beta-adrenoceptor density, but in a subtype-selective manner. Accordingly, pindolol can be subclassified as a partial beta 2-adrenoceptor agonist. PMID- 2907349 TI - Adrenaline-induced amplification of sympathetic activity during rest and stress: inhibition by non-selective and beta 1-selective beta-adrenoceptor blockade. AB - In a placebo-controlled randomized cross-over trial the effects of non-selective (bopindolol, 1 mg once daily for 1 week) and of beta 1-selective beta adrenoceptor blockade (atenolol, 50 mg once daily for 1 week) on adrenaline induced enhancement of basal and stimulated sympathetic activity were studied in 10 hypertensive subjects. During infusion of adrenaline (20 ng/kg per min) venous plasma adrenaline levels increased into the high physiological range. Resting concentrations of arterial plasma noradrenaline and of the basal production of noradrenaline in the forearm increased significantly (P less than 0.01) during infusion of adrenaline. The increases in these two indices of sympathetic activity were abolished by bopindolol and by atenolol. Arterial noradrenaline, but not noradrenaline production, also increased in response to isometric exercise, cold provocation and mental stress during infusion of adrenaline (P less than 0.05). These amplifications were also abolished by both beta adrenoceptor antagonists. Our findings provide further evidence in man for a stimulatory effect of adrenaline in the physiological range on sympathetic activity. This effect, which is supposed to be mediated by prejunctional beta adrenoceptors, can be blocked not only by non-selective, but also by beta 1 selective beta-adrenoceptor antagonists. PMID- 2907350 TI - Hypotensive and regional haemodynamic effects of fenoldopam and quinpirole in the anaesthetized rat. AB - The effects of systemic administration of the selective dopamine1 receptor agonist fenoldopam and the selective dopamine2 receptor agonist quinpirole on blood pressure and regional haemodynamics were investigated in anaesthetized normotensive Wistar rats. Both compounds produced dose-dependent reductions in blood pressure. Mesenteric and renal blood flow were enhanced by fenoldopam, but reduced by quinpirole. Hindquarter blood flow was not modified by fenoldopam, but was increased by quinpirole. The calculated vascular resistances were reduced by both compounds in the three vascular beds. The effects of fenoldopam were antagonized by SCH 23390 but SCH 23390 did not affect those of quinpirole. The effects of quinpirole, but not those of fenoldopam, were antagonized by domperidone. Hexamethonium abolished the effects of quinpirole without affecting those of fenoldopam. These results indicate that the hypotensive effects of fenoldopam and quinpirole are due to stimulation of postsynaptic dopamine1 and neuronal dopamine2 receptors, respectively, resulting in differential regional haemodynamic effects. PMID- 2907351 TI - Pharmacological actions of synthetic atrial natriuretic factor on coronary vascular smooth muscle. AB - The pharmacological activities of synthetic atrial natriuretic factor (ANF) on cat coronary artery were studied in vitro. In the preparation of isolated cat coronary artery perfused at a constant flow, ANF (3-300 nM) decreased perfusion pressure in a concentration dependent manner, indicating coronary vasodilating activity. ANF also relaxed feline coronary strips when contracted by U-46,619, CTA2, angiotensin II, serotonin, leukotriene C4 and D4. This relaxant effect was independent in the presence of endothelial cells and occurred in the presence of guanylate cyclase inhibitor, methylene blue. ANF had no direct effect on electrically driven isolated cat papillary muscles signifying a lack of direct inotropic activity. It can be concluded that ANF may potentiate coronary vasodilation and therefore contribute to coronary regulation, without directly altering myocardial performance. PMID- 2907352 TI - [Recessive human cancer susceptibility genes]. PMID- 2907353 TI - [Progress in molecular genetic study of the complement system. Genetic diagnosis of congenital complement deficiencies and abnormalities]. PMID- 2907354 TI - [Immunologic analysis of families with complement receptor deficiency]. PMID- 2907355 TI - [Abnormality of LDL receptor genes in familial hypercholesterolemia and the genetic diagnosis]. PMID- 2907356 TI - [Pathogenic substances in Parkinson disease and new therapeutics considering the etiologic mechanism]. PMID- 2907357 TI - [Progress in the study of brain receptors]. PMID- 2907358 TI - [Commercially available control sera contaminated with anti-HIV antibody, HIV antigen and anti-ATLA antibody]. PMID- 2907360 TI - No alteration of monoamines and GABA systems in the kindled rat brain. PMID- 2907361 TI - Immunoreactive somatostatin contents in the cerebrospinal fluid of children with various types of epilepsy. PMID- 2907359 TI - Early ocular manifestations of Korean hemorrhagic fever. PMID- 2907362 TI - [The effect of almitrine on hypoxic pulmonary vasoconstriction in isolated perfused rat lungs]. PMID- 2907363 TI - [Introduction to the 16th Retinology Symposium]. PMID- 2907364 TI - Clostridium perfringens enterotoxin. AB - Current knowledge of CPE action is briefly summarized in Figure 1. After specific binding to a protein receptor(s), the entire CPE molecule rapidly inserts into membranes forming a complex of 150,000 Mr. Almost simultaneously with insertion, there is a sudden change in ion fluxes. The molecular events behind the induction of ion flux changes remain undefined, but might involve either direct formation of membrane pores by CPE or activation of pre-existing membrane pores. As intracellular ion levels change, cellular metabolism is affected and processes such as macromolecular syntheses are inhibited. One of the ion flux effects resulting from CPE treatment involves increased Ca2+ influx; as more Ca2+ enters the cell, morphologic damage and permeability alterations for larger molecules occur. It remains to be determined if both morphologic damage and larger permeability alterations are necessarily linked but, for example, it could be envisioned that CPE-induced Ca2+ influx causes a cytoskeletal collapse leading to altered membrane permeability. The cytoskeleton has been shown to be sensitive to intracellular Ca2+ levels and is important in normal membrane structure/function relationships. As the cumulative effects of CPE inhibit cellular metabolism, cell death occurs. The precise irreversible CPE lethal action still must be identified. As CPE-treated intestinal epithelial cells die in vivo, histopathologic damage appears. This damage results in loss of normal intestinal function causing secretion of fluids and electrolytes. This effect is clinically manifested as diarrhea. The strongly cytotoxic action of CPE clearly distinguished the action enterotoxin from STa or CT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2907365 TI - Cloning of the adenylate cyclase genetic determinant of Bordetella pertussis and its expression in Escherichia coli and B. pertussis. AB - A recombinant plasmid, pRMB1, identified from a gene library of B. pertussis, restored adenylate cyclase (AC) and haemolysin (HLY) activities to B. pertussis BP348 (a Tn5-insertion mutant deficient in both these activities). B. pertussis BP348 was considerably less virulent than wild type strains of B. pertussis when 3-week-old mice were challenged intranasally; possession of pRMB1 restored virulence. Neither AC nor HLY activities were expressed in E. coli harbouring pRMB1. However, expression of calmodulin-responsive AC was obtained in E. coli when restriction fragments of pRMB1 were subcloned into other vectors; expression depended on the lac and tac promoters of these vectors. The enzyme was not readily solubilized from urea extracts of E. coli and required sonication for efficient release. One plasmid conferred a specific AC enzymic activity to E. coli which was greater than that for wild type B. pertussis strains. Unlike extracts of B. pertussis, extracts from E. coli expressing enzymic AC activity, did not elevate cAMP levels in S49 lymphoma cells. A second plasmid, pRMB2, was identified from the gene library, which contained a trans-acting regulatory determinant required for expression of AC, HLY and other virulence-associated factors in B. pertussis. PMID- 2907366 TI - Mutations in cloned Escherichia coli P fimbriae genes that makes fimbriae production resistant to suppression by trimethoprim. AB - The effect of sublethal concentrations of trimethoprim on the expression of P fimbriae was tested in Escherichia coli HB101 recombinant strains. Fimbriation was inhibited at trimethoprim concentrations down to at least 1/64 of the minimal inhibitory concentration. However, the expression of the P fimbrillin by recombinant plasmids containing deletions in front of the fimbrillin gene did not respond to the inhibitory effect of trimethoprim indicating that trimethoprim may act at the level of gene regulation. PMID- 2907367 TI - L-methylmalonyl-CoA mutase from human placenta. PMID- 2907368 TI - A role for gamma-aminobutyric acid (GABA) in the evolution of delayed neuronal death following ischemia. AB - A series of putative neuroprotective agents was tested to determine their efficacy in preventing the loss of the CA 1 neurons of the hippocampus at 4 days following 5 min of bilateral ischemia in the gerbil. Agents associated with the GABAergic system were determined to be the most effective, but only when given prior to the ischemic episode, suggesting that there was a gamma-aminobutyric acid (GABA)-related event during ischemia which triggers the delayed neuronal death of these cells. In this report, the unidirectional release of GABA and glutamate from gerbil hippocampal slices was determined under conditions mimicking anoxia and/or ischemia. Pentobarbital, the most effective of the GABAergic agents, had little or no effect on the time-dependent release of glutamate. In contrast, pentobarbital reduced in release of GABA in both anoxia and ischemia, but only after 25 to 30 min of incubation. PMID- 2907369 TI - Identification of the Klebsiella pneumoniae glnB gene: nucleotide sequence of wild-type and mutant alleles. AB - The glnB gene of Klebsiella pneumoniae, which encodes the nitrogen regulation protein PII, has been cloned and sequenced. The gene encodes a 12429 dalton polypeptide and is highly homologous to the Escherichia coli glnB gene. The sequences of a glnB mutation which causes glutamine auxotrophy and of a Tn5 induced Gln+ suppressor of this mutation were also determined. The glutamine auxotrophy was deduced to be the result of a modification of the uridylylation site of PII, and the suppression was shown to be caused by Tn5 insertion in glnB. The 3' end of an open reading frame of unknown function was identified upstream of glnB and may be part of an operon containing glnB. Potential homologues of glnB encoding polypeptides extremely similar in sequence to PII were identified upstream of published sequences of the glutamine synthetase structural gene (glnA) in Rhizobium leguminosarum, Bradyrhizobium japonicum and Azospirillum brasilense. PMID- 2907370 TI - Characterization of human placental opioid receptors by 3H-ethylketocyclazocine and 3H-naloxone binding. AB - The human placenta contains membrane bound opioid receptors. The binding of the antagonist naloxone and the fairly kappa-selective agonist EKC were studied in the microvillous membrane fraction. In both cases high affinity binding sites were detected with Kd values in the nanomolar range. A series of kappa-selective ligand (PD-117302, EKC, and U-50, 488H) were tested in displacement experiments, and found to be potent inhibitors of agonist and antagonist binding. It was confirmed that large percentage of the binding is associated with the kappa sub type which is of current interest, in that it shows distinctive pharmacology and distribution and is selective for the natural opioid polypeptide, dynorphin. PMID- 2907371 TI - A zonal pattern of neuroglial cells during the development of the intermediate lobe of the rat pituitary. AB - In this paper the development of the intermediate lobe (IL) of the pituitary of the rat is described using alkaline phosphatase (AP) (EC 3.1.3.1.) enzyme histochemistry and stage-specific embryonic antigen 1 (SSEA-1) immunocytochemistry. SSEA-1 and AP are co-localized during late development and reveal the existence of two cytochemically different cell types within the IL, i.e. SSEA-1/AP-positive and SSEA-1/AP-negative cells. The SSEA-1/AP-positive cells are initially arranged along the hypophyseal lumen, in a number of longitudinally oriented zones. alpha-Melanocyte-stimulating hormone (alpha-MSH) immunoreactivity is expressed in the SSEA-1/AP-negative cells from E20 onwards. Eventually the SSEA-1/AP-positive cells develop into a layer of cells covering the luminal surface of the IL lobules. These cells represent the glio-epithelial or neuroglial cells of the IL. PMID- 2907372 TI - Autoradiographic and electrophysiological evidence for excitatory amino acid transmission in the periaqueductal gray projection to nucleus raphe magnus in the rat. AB - Selective retrograde labelling was used as an autoradiographic method to identify possible excitatory amino acid afferents to nucleus raphe magnus (NRM). Injections of 25-50 nl 10(-2) or 10(-3) M D-[3H]aspartate into the NRM resulted in prominent labelling of cells in ventrolateral mesencephalic periaqueductal gray (PAG). Electrophysiologically, stimulation in ventrolateral PAG excited cells in NRM with a latency of 2-12 ms. With many cells, microelectrophoretic application of the excitatory amino acid antagonists, kynurenate and gamma-D glutamyl-glycine, resulted in a reversible reduction of the PAG-evoked response. Selective antagonists of N-methyl-D-aspartate (NMDA) were less effective. It is suggested that neurones in the ventrolateral PAG projecting to NRM utilize an excitatory amino acid or structurally related compound as a transmitter, and that this transmitter acts on receptors of the non-NMDA type. PMID- 2907373 TI - The D1 agonist SKF 38393 inhibits the antiparkinsonian activity of the D2 agonist LY 171555 in the MPTP-treated marmoset. AB - Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to common marmosets induced persistent motor deficits. Administration of the D1 agonist SKF 38393 (2.5-20 mg/kg, i.p.) caused a dose-dependent increase of this akinesia. Administration of the D2 agonist LY 171555 (0.3 mg/kg, i.p.) reversed the motor deficits induced by MPTP treatment. Pretreatment of animals with SKF 38393 (2.5 20 mg/kg, i.p.) caused dose-dependent inhibition of the anti-parkinsonian action of LY 171555 (0.3 mg/kg i.p.). In primates SKF 38393 does not reverse motor deficits induced by MPTP and inhibits the actions of a D2-agonist. PMID- 2907374 TI - Further characterization of tolerance to the corticosterone-elevating effect of pergolide in rats. AB - Four daily injections of pergolide, an ergoline dopamine agonist, made male rats tolerant to the corticosterone-elevating effects of an acute injection of pergolide on the fifth day. This tolerance occurred not only to acute treatment with pergolide, but also to other dopamine agonists differing in structure, potency and receptor subtype selectivity. Plasma corticosterone was elevated following administration of opioid or serotonin agonists in both vehicle- and pergolide-pretreated rats. The current findings strengthen the conclusion that tolerance to the acute elevation of corticosterone by pergolide is not due to impairment of pituitary-adrenocortical function but instead to changes in dopamine receptors that initiate the response. PMID- 2907375 TI - The kainate/quisqualate receptor antagonist, CNQX, blocks the fast component of spontaneous epileptiform activity in organotypic cultures of rat hippocampus. AB - Intracellular recordings were made from CA1 pyramidal neurones of hippocampus maintained in organotypic culture. Both spontaneous interictal and ictal epileptiform activity was observed. CNQX, an antagonist at kainate/quisqualate but not at N-methyl-D-aspartate (NMDA)-sensitive excitatory amino acid receptors depressed but did not abolish spontaneous epileptiform activity. Addition of the specific NMDA receptor antagonist D-2-amino-5-phosphonovalerate (D-APV) abolished the remaining activity. Similar effects were observed on electrically evoked excitatory post synaptic potentials (EPSPs). This suggests a role for endogenous excitatory amino acids acting at both kainate/quisqualate and NMDA sensitive excitatory amino acid receptors in the generation and maintainance of epileptiform activity within these organotypic cultures. PMID- 2907376 TI - Dopaminergic dorsal raphe neurons in cats and monkeys are sensitive to the toxic effects of MPTP. AB - Tyrosine hydroxylase immunohistochemical analysis of the dorsal raphe nucleus (DRN) of severely parkinsonian MPTP-treated cats and cynomolgus monkeys revealed a marked loss of catecholaminergic neurons in this region. Cell loss was more extensive in the ventral portion of the nucleus with a relative sparing of neurons in the dorsal-most portions of the DRN. These results demonstrate that catecholaminergic neurons other than those in the ventral mesencephalon and the locus ceruleus are affected by the toxic effects of MPTP. PMID- 2907377 TI - Amino acid neurotransmitter deficits in adult Down's syndrome brain tissue. AB - Neurotransmitter amino acids have been measured in several brain regions taken postmortem from 5 adults cases of Down's syndrome and 6 age-matched control subjects. A significant deficit of glutamate was found in the hippocampus in Down's syndrome, and gamma-aminobutyric acid was reduced in the hippocampus and temporal cortex in those patients with neocortical neurofibrillary tangles. These results are consistent with losses of cortical neurones containing these neurotransmitters, and resemble the deficits exhibited by the more severely affected cases of Alzheimer's disease. PMID- 2907378 TI - Co-localization of tyrosine hydroxylase (TH)- and serotonin (5-HT)-immunoreactive innervation in the rat pituitary gland. AB - Adult male Sprague-Dawley rats were examined for possible co-localization of tyrosine hydroxylase (TH) and serotonin (5-HT) within innervation of the pituitary neurointermediate lobe. Use of sheep antiserum to TH and a secondary antibody coupled to fluorescein isothiocyanate (FITC), followed by rabbit anti-5 HT, then rhodamine-coupled second antibody, produced co-existent staining in some, but not all fibers of both the neural and intermediate lobes, using paraffin embedded tissues. Application of a combination of the two primary antibodies followed by sequential application of secondary antibody also resulted in co-localized antigens in selected fibers. Multiple 'classic' neurotransmitters within the same nerve terminals may modulate selected areas of endocrine tissue to control hormone release. PMID- 2907379 TI - [Cibalen poisoning in an infant]. AB - A toxicological investigation of urine could finally explain abnormal neurological symptoms with apnea. 2 Cibalen-suppositories for children were given to an 7 week old infant as treatment of an upper respiratory infect. 12 hours were between the application of the 2 suppositories. 2 hours after the second application coma, hypertonus, opisthotonus, miosis and depression of ventilation were found. 10 hours later an apnea occurred. These symptoms were due to the synergistic effect of Phenobarbital, Aminophenazon and Codeinphosphat in an overhigh dose. PMID- 2907380 TI - [Phobia in childhood and adolescence]. PMID- 2907381 TI - Neurofibrillar long-range amacrine cells in mammalian retinae. AB - A distinct population of wide-field, unistratified amacrine cells are shown to be selectively stained by using neurofibrillar methods in rabbit and cat retinae. Their cell bodies may be located in the inner nuclear, inner plexiform or ganglion cell layers and they branch predominantly in stratum 2 of the inner plexiform layer. Characteristically, each cell has two or more long-range distal processes which extend for 2-3 mm beyond a more symmetrical, proximal dendritic field of 0.6-0.8 mm diameter. Although the neurofibrillar long-range amacrines account for less than 1 amacrine in 500, they achieve effective coverage of the retina by both the proximal and distal dendrites. PMID- 2907382 TI - Feature detection in human vision: a phase-dependent energy model. AB - This paper presents a simple and biologically plausible model of how mammalian visual systems could detect and identify features in an image. We suggest that the points in a waveform that have unique perceptual significance as 'lines' and 'edges' are the points where the Fourier components of the waveform come into phase with each other. At these points 'local energy' is maximal. Local energy is defined as the square root of the sum of the squared response of sets of matched filters, of identical amplitude spectrum but differing in phase spectrum by 90 degrees: one filter type has an even-symmetric line-spread function, the other an odd-symmetric line-spread function. For a line the main contribution to the local energy peak is in the output of the even-symmetric filters, whereas for edges it is in the output of the odd-symmetric filters. If both filter types respond at the peak of local energy, both edges and lines are seen, either simultaneously or alternating in time. The model was tested with a series of images, and shown to predict well the position of perceived features and the organization of the images. PMID- 2907383 TI - Identification of molecules in leech extracellular matrix that promote neurite outgrowth. AB - The molecular composition of the substrate is of critical importance for neurite extension by isolated identified leech nerve cells in culture. One substrate upon which rapid growth occurs in defined medium is a cell-free extract of extracellular matrix (ECM) that surrounds the leech central nervous system (CNS). Here we report the co-purification of neurite-promoting activity with a laminin like molecule. High molecular mass proteins from leech ECM purified by gel filtration exhibited increased specific activity for promoting neurite outgrowth. The most active fractions contained three major polypeptide bands of ca. 340, 250 and 220 kDa. Electron microscopy of rotary-shadowed samples showed three macromolecules, one of which had a cross-shaped structure similar to vertebrate laminin. A second six-armed molecule resembled vertebrate tenascin and a third rod-like molecule resembled vertebrate collagen type IV. The most active fractions contained a protein of ca. 1 MDa on non-reducing gels with disulphide linked subunits of ca. 220 and 340 kDa, with cross-shaped laminin-like molecules. We conclude that a laminin-like molecule represents a major neurite promoting component present in leech ECM. The experiments represent a first step in determining the location of leech laminin within the CNS and assessing its role in neurite outgrowth during development and regeneration. PMID- 2907384 TI - Agonists at presynaptic receptors on sympathetic nerves differentially affect two phases of the contractile response in the rat vas deferens. AB - A series of adrenoceptor agonists were investigated for their prejunctional effects on field stimulated rat vas deferens. Tissues were stimulated in 10 s trains of impulses, frequency 10 Hz, every 100 s. This produced a biphasic response comprising an initial twitch followed by a prolonged, plateau phase of contraction. The order of potency for a series of alpha 2-agonists against the twitch phase of contraction was UK14304 greater than clonidine greater than noradrenaline = alpha-methyl noradrenaline greater than B-HT920. The same order of potency was observed against the plateau phase, but approximately 10 fold higher concentrations of agonist were needed. Surprisingly, B-HT920 was inactive against the plateau phase of contraction. Characteristic differences in the slopes and maximum responses of the dose-response curves to the imidazolines (UK14304 and clonidine) and the beta-phenethylamines (noradrenaline and alpha methyl noradrenaline) were seen against both phases of contraction. It is concluded that the two phases of contraction are influenced by activation of two distinct heterogeneous populations of prejunctional alpha 2-adrenoceptors. PMID- 2907385 TI - Photo- and thermal-activation of bovine liver urocanase. PMID- 2907386 TI - [Effects of selective D-1 and D-2 dopamine antagonists on methamphetamine-induced behavioral sensitization]. PMID- 2907387 TI - Noradrenergic effects in tardive dyskinesia, akathisia and pseudoparkinsonism via the limbic system and basal ganglia. AB - 1. This paper proposes that the neuropsychiatric symptoms of tardive dyskinesia, akathisia and pseudoparkinsonian tremor are modulated by a noradrenergic pathway that projects from the locus coeruleus to the limbic system. 2. The proposed pathway is found to the consistent with neuroanatomical and neurochemical data in the literature. 3. The proposed pathway is found to be clinically consistent with observations by ourselves and others on the efficacy of clonidine and beta adrenoreceptor blockers like propranolol for treating akathisia and pseudoparkinsonian tremor. It is also consistent with reports by ourselves and others that some patients with tardive dyskinesia benefit from treatment with propranolol or clonidine. 4. Noradrenergic modulation of the limbic system by way of the locus coeruleus accounts for a number of clinical observations, such as the worsening of tardive dyskinesia by stress, the greater risk for tardive dyskinesia in patients with affective disorder, the time-of-onset of tardive dyskinesia, and the coexistence of tardive dyskinesia and pseudoparkinsonism. 5. The functional significance of beta-adrenoreceptors in the basal ganglia is considered from an evolutionary perspective. 6. The model proposed in this article appears to have considerable heuristic value because it may further our understanding of Gilles de la Tourette syndrome and attention deficit disorder (hyperkinesis). PMID- 2907388 TI - [Comparative analysis of some mechanical properties of solder joints with a copper-aluminum alloy, using two types of low-fusing solder]. PMID- 2907389 TI - [Morphine analgesics]. PMID- 2907390 TI - [Non-amphetamine analeptics]. PMID- 2907391 TI - [Ways to develop and extend perestroika (results of the 19th All-Union Conference of the Communist Party)]. PMID- 2907392 TI - A clinical study on vecuronium in children: a comparison with fazadinium and pancuronium. PMID- 2907393 TI - Polyorchidism associated with cryptorchidism. PMID- 2907394 TI - [Analysis of parasitic zymodemes]. PMID- 2907395 TI - Responses of neurons in somatosensory cortical area II of cats to high-frequency vibratory stimuli during iontophoresis of a GABA antagonist and glutamate. AB - Areas in the second somatic sensory cortex (SII) of cats that responded vigorously to low-amplitude, high-frequency vibratory stimulation were mapped with respect to the surrounding somatotopic organization. Neurons with these properties were found in the posterior and medial parts of the distal forelimb zone and were judged as receiving input from Pacinian mechanoreceptors. The responses of these neurons to sinusoidal vibrotactile stimulation were studied during iontophoretic administration of glutamate or bicuculline methiodide (BMI) to determine if the temporal fidelity of these cortical neurons was controlled by inhibitory circuits that used gamma-aminobutyric acid (GABA) as a neurotransmitter. The data from 19 Pacinian-sensitive neurons were analyzed for changes in the mean firing rate, the percentage of entrainment, and the pattern of periodicity as revealed by autocorrelograms and interval histograms. Iontophoresis of BMI or glutamate caused significant increases in mean firing rates during low- and high-frequency vibratory stimulation. The pattern of increased activity produced by BMI was characterized by a small, yet significant, reduction in the percentage of entrainment, whereas glutamate caused smaller and fewer significant changes in this measure. Analysis of autocorrelation and interval histograms suggested that BMI increased the probability of firing on consecutive stimulus cycles in small segments of the stimulus duration. PMID- 2907396 TI - Immunocytochemical localization of peptides in the endocrine pancreas of the snakes Vipera aspis and Natrix maura. AB - The endocrine pancreas of Vipera aspis and Natrix maura has been investigated by immunocytochemistry for the presence of six peptides reported to occur in Mammals or in Reptiles. Gastrin/CCK and PP were absent in the endocrine cells, VIP was located within nerve terminals only. Insulin, Glucagon, and Somatostatin were localized both in Vipera and Natrix, generally with a ring of D (Somatostatin) cells surrounding a core of Glucagon (A) and Insulin (B) producing cells; however frequent clusters of D cells are intermingled with the other endocrine cells. Statistical evaluations on the percentages of these 3 cell types showed preponderance of A cells in Natrix whereas in Vipera no significant difference was found between the number of A and B cells. The D cells showed a uniform distribution in the pancreas of the 2 studied species, in any case with a percentage slightly inferior to those of B cells. PMID- 2907397 TI - Deterioration of B cell proliferation correlates with dendritic reticulum cell destruction in germinal centers of an AIDS patient. Case study. AB - A lymph node from a bisexual Caucasian male infected with human immunodeficiency virus (HIV) and in the persistent generalized lymphadenopathy (PGL) stage was studied. Dendritic reticulum cells (DRCs) were well preserved in over half of the germinal centers (GCs), while in the rest, they showed marked destruction, producing patchy or rather wide DRC-depleted areas. Proliferation-associated antigens, i.e., PC antigen and DNA-polymerase alpha, were demonstrated in nuclei of germinal center B cells in areas where the DRC network was intact, while they were prominently depleted in areas where the DRC network was lost. The p-24 viral core antigen was shown to be localized in DRCs, especially those in the process of degeneration. These results suggest that the DRC in this patient, when infected with HIV, were destroyed, and that the resulting DRC depletion led to the suppression of B cell proliferation in GCs. PMID- 2907398 TI - [Pharmacological therapy of anaphylactic disorders]. PMID- 2907399 TI - [Unusual findings during orchidopexy]. PMID- 2907400 TI - [Study of Culicidae in Firaisam-Pokontany of Ambohimanjaka in the environs of Tananarive: results of a longitudinal study, in particular on the vectorial transmission of malaria]. PMID- 2907401 TI - [Entomopathogenic mushrooms of the genus Coelomomyces in Madagascar]. PMID- 2907402 TI - Prenatal diagnosis and carrier detection by DNA studies in a Duchenne muscular dystrophy family with no living affected male. AB - Restriction fragment length polymorphism studies and gene dosage analysis using the intragenic probes pERT87 were used to detect deletions in potential carriers in a family with Duchenne muscular dystrophy in which the only affected male was deceased. Two females were found to have inherited the paternal pERT87 alleles but not the maternal alleles, suggesting that they have inherited the pERT87 deletion from their mothers. The hybridization signals of pERT87 from these two females upon gene dosage analysis also suggested that they had a single copy of pERT87. The chorionic villi of a male fetus from one of these two females was found to be deleted for pERT87, suggesting that it was affected. This result confirmed the carrier status of the mother. PMID- 2907403 TI - Restriction fragment length polymorphism and chromosome mapping of a mouse homeo box gene, Hox-2.1. AB - Restriction endonuclease fragment length polymorphisms (RFLPs) were found using the cDNA probe Hox-2.1 for the homeo box-2.1 gene in the mouse. Polymorphism was detected in restriction patterns generated by fragments from HindIII digestion. The great majority of laboratory strains of mice carries the Hox-2.1a allele. Only two laboratory strains carry the Hox-2.1b allele. Among strains of wild origin, the European subspecies (Mus m. domesticus, M. m. brevirostris, and M. m. musculus) and some Asian subspecies (M. m. castaneus) carry the Hox-2.1a allele. The subspecies from Far Eastern countries (M. m. molossinus, Chinese mice of wild origin, and M. m. yamashinai) carry the Hox-2.1b allele. Using the RFLP, the Hox 2.1 gene was mapped on chromosome 11. Three-point cross test data showed that the recombination frequency is 29.6% between the Hba and the Hox-2.1 genes and 23.5% between the Hox-2.1 and the Es-3 genes. The gene order of Hba-Hox-2.1-Es-3 has been confirmed. PMID- 2907404 TI - Genetic determinants of glutamine synthetase in Drosophila melanogaster: a gene for glutamine synthetase I resides in the 21B3-6 region. AB - Recombinational and deletion mapping of electrophoretic variants of the glutamine synthetase I isozyme (GSI) in Drosophila melanogaster locates the gene in the 21B region on the second chromosome. We have conducted a genetic analysis of the region extending cytologically from 21A to 21B4-6. Recessive lethal mutations were generated by ethyl methanesulfonate (EMS) and ethyl nitrosourea (ENU) mutagenesis and by hybrid dysgenesis (HD). These lethals fall into seven functional groups, which were partially ordered by complementation with cytologically defined deficiencies of this region generated by hybrid dysgenesis. Two of the EMS- and two of the ENU-induced lethals fulfill biochemical criteria expected for null alleles of the GSI gene. PMID- 2907405 TI - [Studies on the biological function of the nucleotide base of vitamin B12]. AB - Studies on the coenzyme activity of some nucleotide base analogues of adenosylcobalamine in the dioldehydratase and methyl-malonyl-CoA mutase systems resulted in fundamental differences: Contrary to dioldehydratase the coenzyme activity remains in the methyl-malonyl-CoA mutase system when adenosyl-cobamides with a strongly modified nucleotide base are studied. The analogues give a good growth response with Escherichia coli. In the growth test with Lactobacillus leichmanii only the cobamides that do not have substituted nucleotide bases in the positions 2 or 3 of their imidazole ring are active. PMID- 2907406 TI - Amino-acid sequence homology of a polymorphic cellular protein from human lymphocytes and the chaperonins from Escherichia coli (groEL) and chloroplasts (Rubisco-binding protein). AB - The human p60 (Mr 60,000) is an abundant protein in the two-dimensional electrophoresis pattern of the cellular proteins of human mitogen-stimulated lymphocytes. The p60 shows as remarkable characteristic a genetic polymorphism with two different alleles. Electrotransfer of this protein from two-dimensional gels onto siliconized glass fiber sheets and subsequent amino-acid sequence analysis has revealed a striking homology to the known bacteria and plant chaperonins, the groEL and the Rubisco-subunit-binding protein. From this sequence homology we conclude that we have identified the human chaperonin homologue. PMID- 2907407 TI - CD4+: neopterin ratio significantly improves correlation with the Walter Reed staging system if compared with CD4+ and neopterin considered separately. PMID- 2907409 TI - Regulation of human natural cytotoxicity by enkephalins and selective opiate agonists. AB - This study reports a bidirectional effect of the enkephalins and selective opiate receptor agonists on human natural killer (NK) cell activity. Peripheral blood mononuclear cells (PBMC) were obtained from healthy donors and enriched for T lymphocytes and large granular lymphocytes (LGL) by passage over nylon wool columns. Nylon wool nonadherent cell populations were preincubated for 18 h in the presence of fetal bovine serum with and without methionine-enkephalin, leucine-enkephalin, dynorphin (fragment 1-13), [D-Ser2]-leucine-enkephalin-Thr (DSLET), and [D-Ala2,N Me-Phe4, Gly-ol5]-enkephalin (DAGO). NK activity was measured by a standard 51Cr release assay with radiolabeled K562 cells. The cytolytic capacity of low NK responder populations was enhanced by the endogenous opioids while the NK activity of high responder populations was suppressed. These results suggest an immunoregulatory action of opioid peptides on NK activity. This possibility was confirmed using a serum-free system in conjunction with recombinant interferon-alpha. In addition, the classic opioid receptor antagonist naloxone displayed both antagonist and direct immunomodulatory properties, which may indicate the presence of lymphocyte derived opioid peptides in the culture system. PMID- 2907410 TI - Determination of the beta-blocker betaxolol and labelled analogues by gas chromatography/mass spectrometry with selected ion monitoring of the alpha cleavage fragment (m/z 72). AB - Low concentrations of betaxolol in blood plasma and physiological buffers were determined by selected ion monitoring of the intense m/z 72 fragment [CH2 = NH CH(CH3)2]+ formed by electron impact ionization of the O-trimethylsilyl derivative. At a mass spectrometric resolution of 3000, fewer potentially interfering peaks were seen than at low resolution. There remained a chemical interference, corresponding to 100 pg/sample, which arose during treatment of the samples. This method is more sensitive than previous ones, but it is restricted to situations where the specificity can be controlled. When the m/z 72 fragment was mass-shifted by using betaxolol appropriately labelled with deuterium or 13C, both the interference and the baseline noise were greatly reduced; concentrations of labelled betaxolol as low as 10-20 pg/sample can be determined with little difficulty. PMID- 2907408 TI - Comparative effects of rilmenidine and clonidine on bronchial responses to histamine in asthmatic subjects. AB - 1. The effects of pretreatment with clonidine and rilmenidine, a new alpha 2 adrenoceptor agonist, on the bronchial responses to inhaled histamine were studied on 3 different days in a controlled, double-blind, randomized study in 12 asymptomatic asthmatic subjects. Clonidine and rilmenidine were orally administered as single and equipotent doses of 150 micrograms and 1 mg, respectively. All the subjects were non-smokers with normal lung function tests (forced expiratory volume in one second (FEV1) = 97 +/- 10% predicted FEV1). 2. Histamine (first dose = 543 nmol) was delivered by a breath activated dosimeter (DeVilbiss no. 646 nebulizer) every 5 min; FEV1 was measured in triplicate after each dose and the largest value was analyse. The three dose-response curves were compared by analysis of variance. 3. Both clonidine and rilmenidine decreased arterial blood pressure in all subjects. There was no difference in baseline values and pre-challenge values of FEV1 after placebo, clonidine and rilmenidine on the 3 study days. Compared with placebo, both rilmenidine and clonidine significantly increased the bronchial responses to histamine (P less than 0.05 and P less than 0.01 respectively) an effect which was significantly more marked with clonidine than rilmenidine (P less than 0.05). 4. We suggest that the enhancement of bronchial responsiveness to histamine by clonidine and rilmenidine may result from their effects on both central and peripheral alpha 2 adrenoceptors, and that the lesser aggravation of histamine-induced bronchial obstruction in asthmatic subjects on rilmenidine might be explained by its lesser central and/or greater peripheral effects than clonidine. PMID- 2907411 TI - Analysis of almitrine and its metabolites in plasma using on-line fast atom bombardment liquid chromatography/mass spectrometry. AB - To validate a recently developed liquid chromatography/ultraviolet (LC/UV) method in a pharmacokinetic study of Vectarion (almitrine) where the unchanged drug, its five metabolites and an internal standard are analysed, on-line fast atom bombardment liquid chromatography/mass spectrometry (FAB LC/MS) with a moving belt interface has been used. Since the liquid chromatographic conditions required the use of perchloric acid FAB was chosen as ionization mode for the involatile perchlorates formed in the liquid chromatographic process. The use of FAB LC/MS allows the detection of the protonated molecular ions of all the components in the mixture. Furthermore, all the compounds show an intense peak at m/z 203, presenting a liquid chromatographic profile which is very similar to the profile obtained with UV detection. PMID- 2907412 TI - [The association of non-insulin-dependent diabetes mellitus with the genes responsible for carbohydrate and lipid metabolism in the Chinese]. PMID- 2907413 TI - [Prenatal diagnosis of Duchenne muscular dystrophy using DNA RFLP analysis]. PMID- 2907414 TI - [Detection of antigens in blood smears of patients with epidemic hemorrhagic fever using the rosette cell formation SpA method]. PMID- 2907415 TI - The suppression of blood growth hormone level by somatostatin infusion in patients with active acromegaly. PMID- 2907416 TI - Morphine can stimulate prolactin release independent of a dopaminergic mechanism. AB - Prolactin release is controlled by prolactin-release inhibiting factor (PIF), possibly dopamine, and an unidentified putative hypothalamic prolactin-releasing factor (PRF). Morphine and related opioids may indirectly stimulate prolactin release by inhibiting PIF release and (or) by stimulating putative PRF release. In the present study, we have completely blocked the dopaminergic receptors in normal male rats by pretreatment with a large dose of pimozide (3 mg/kg) to demonstrate if putative PRF has a role in morphine-induced prolactin release. Morphine sulfate (10 mg/kg) was still able to stimulate prolactin release in the rat without any functional dopaminergic PIF receptors. When naloxone (3 mg/kg) was injected 20 min before the morphine in the pimozide-treated rat, plasma prolactin concentration was not affected by morphine indicating that the stimulatory effect of this opioid on prolactin release in the pimozide-pretreated rat was mediated by mu-receptors. We can conclude that morphine can stimulate prolactin release through a mechanism apparently independent of dopaminergic receptors, one possible route being through a putative PRF. PMID- 2907417 TI - Evidence for regionally selective changes in response to potassium chloride but not vasopressin or methoxamine in vasculature from diabetic rats. AB - In the present study we examined the contractile responses of aortae and mesenteric and femoral arteries taken from rats treated 3 weeks previously with streptozotocin (55 mg/kg, i.v.) or saline (1 mL/kg, i.v.) to vasopressin, potassium chloride, and methoxamine. The dose-response curves obtained with vasopressin and methoxamine were not significantly different between control and diabetic animals. However, both the diabetic mesenteric and femoral arteries showed a significantly (p less than 0.05) greater maximum response to potassium chloride as compared with their respective controls. The reactivity of the diabetic aortae to this agonist was not different. It is concluded that while the contractile responses of the diabetic tissues were normal when the agonist was vasopressin or methoxamine, there would appear to be regionally selective changes in responsiveness to potassium chloride. PMID- 2907418 TI - [Genes in atherosclerosis]. PMID- 2907420 TI - [Nursing care of patients using 654-2 in the prevention and treatment of epidemic hemorrhagic fever renal failure]. PMID- 2907419 TI - Role of sequence amplification in the generation of nematode mitochondrial DNA polymorphism. AB - Romanomermis culicivorax, an obligate parasitic nematode of mosquitos, possesses an unusually large mitochondrial genome. Individuals are monomorphic for one of several mitochondrial DNA (mtDNA) size variants ranging from 26-32 kb. In this report, we demonstrate that the mitochondrial genome size differential in three isofemale lineages is due to the presence of mtDNA sequences amplified to different copy numbers within each mtDNA molecule. Restriction enzyme analysis and DNA sequencing studies reveal that each mitochondrial genome contains one of two 3.0 kb repeat types that differ by approximately 30 bp. This difference is primarily due to a short (23 bp) imperfect tandem duplication present within the larger of two polymorphic repeating units. The 3.0 kb reiterated DNA sequences are present as direct, tandem repeats and as inverted portions of the same sequence located elsewhere in the genome. Based on mtDNA analysis of an independently reared R. culicivorax culture, we conclude that events resulting in mitochondrial genome rearrangement occurred in natural field populations prior to propagation within the laboratory. PMID- 2907422 TI - [Problems caused by infection due to the HIV retrovirus]. PMID- 2907421 TI - Inhibitors of sterol synthesis. Studies of the metabolism of 5 alpha-cholest 8(14)-en-3 beta-ol-15-one in Chinese hamster ovary cells and its effects on activities of early enzymes in cholesterol biosynthesis. AB - The metabolism of [2,4-3H]5 alpha-cholest-8(14)-en-3 beta-ol-15-one (I) has been studied in Chinese hamster ovary (CHO-K1) cells which were maintained in a lipid deficient medium. The incorporation of I into the cells was linear with respect to sterol concentration in the medium over the ranges of concentrations studied and was more than 3.5 times that of the uptake of cholesterol. The results of detailed chromatographic analyses of the lipids recovered from the cells after 6 h of incubation with [2,4-3H]I (0.5 microM or 6.0 microM) indicated that most of the 3H was associated with free I. Considerably lesser amounts of the 3H was associated with esters of I. No formation of [3H]cholesterol or [3H]cholesteryl esters (or other C27 monohydroxysterols) from labeled I was observed. The labeled material with the chromatographic behavior of the esters of I gave, after mild alkaline hydrolysis, the free 15-ketosterol which was characterized by the results of chromatographic and cocrystallization studies. Upon transfer of the CHO-K1 cells from a culture medium containing 8% newborn calf serum to the same medium containing 8% lipid-deficient newborn calf serum, increases in the levels of activity of cytosolic acetoacetyl-CoA thiolase and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase and of HMG-CoA reductase were observed. These increases were blocked by the addition of I at a concentration of 1.0 microM. I (1.0 microM) also caused a decrease in the levels of activity of the three enzymes in cells previously grown in medium containing lipid-deficient serum. These results demonstrate that I not only affects the enzymatic reduction of HMG CoA but also the enzymatic formation of this key intermediate in cholesterol biosynthesis. PMID- 2907423 TI - Analysis of cis and trans elements involved in cAMP-inducible gene expression in Dictyostelium discoideum. AB - Expression of the Dictyostelium discoideum pst-cath (CP2) gene is transcriptionally regulated during multicellular development, and the gene is inducible in competent single cells following administration of exogenous cAMP. The 5' flanking region of pst-cath (CP2) that extends from -313 to the Cap site (+1) has previously been shown to contain sufficient cis-acting regulatory elements for proper developmental and cAMP-inducible expression of a foreign gene [Datta and Firtel, 1987, Mol Cell Biol 7:149-159]. The -283 to -201 region includes two exceptional "G-boxes" centered at -233 and -217 respectively, and this approximately 80 bp region is essential for basal as well as regulated expression of the pst-cath (CP2) gene. Here we summarize results obtained from a detailed analysis of a series of linker-scanner mutants and mutants that carry small internal deletions within the essential 80-bp region. Insertion of a synthetic oligonucleotide that includes the downstream G-box is demonstrated to rescue a low level of cAMP-inducible expression following insertion into cassette mutants. The effect of introducing a change in the relative spacing between regulatory elements has also been investigated. We have analyzed nuclear extracts for the presence of DNA-binding proteins that interact specifically with the pst cath (CP2) regulatory region and identified two such putative trans-acting factors: 1) the AT-factor that is observed within a few hours following the onset of starvation and that binds tightly to stretches of alternating adenine-thymine residues (poly(dA-dT]; and 2) the AG-factor that is present in nuclear extracts of aggregated cells. Competition studies have demonstrated significant differences in the affinity that characterizes the binding of the two factors to G-box-containing sequences. The binding specificities of these DNA-binding proteins have been analyzed using gel mobility-shift and DNaseI footprinting assays. PMID- 2907424 TI - [A critical discussion on the current status of drug treatment of brain aging]. PMID- 2907425 TI - Use of benzodiazepines among residents of aged-care accommodation. PMID- 2907426 TI - Bloat in sheep (Ovis aries). AB - 1. Most of the field studies on bloat are conducted with cattle and most of the laboratory experiments seeking to explain the various parameters associated with bloat are done with sheep. 2. Based on grazing behaviour, it would be expected that sheep might bloat more severely than cattle because they selectively choose to eat leaves over stems and chew what they ingest more frequently than cattle. Furthermore, sheep appear to select legumes over grasses because the legumes can be eaten more rapidly. However, because they are selective, sheep eat more slowly than cattle. Despite a higher bloat expectation, bloating in sheep is reported to be less of a problem than in cattle. 3. Although frothing of rumen ingesta was described earlier in cattle as the cause of acute legume bloat, experiments with frothy bloat in sheep preceded those in cattle. 4. Anti-frothing agents were used in sheep before cattle to treat acute legume bloat. 5. Experiments devoted to the study of eructation in ruminants were carried out on sheep, then cattle. 6. Convincing evidence that rumen motility does not cease during acute legume bloat was gathered using sheep. 7. Although the transected tracheal technique for the determination of the volume of eructated gas was developed with cattle, the pathway of eructated gas was confirmed with sheep. 8. All the current evidence accumulated from experiments with sheep supports the hypothesis that death due to legume bloat is caused by acute neural, respiratory, and cardiovascular insult resulting from the effect of the distended rumen on thoracic viscera, diaphragm, intercostal muscles, and the abdominal vena cava. 9. Experiments with sheep and cattle being fed scabrous and nonscabrous diets similar in chemical composition show that sheep are more resistant than cattle to the increase in intrarumen pressure, decline in rumen contraction amplitude, and decrease in rumen contraction frequency caused by nonscabrous diets. 10. The sequence of events in the reticulorumen during primary and secondary contractions previously described following visual and palpation experiments with cattle was confirmed by the use of myoelectrodes implanted in the various sacs of the reticulorumen of sheep. 11. Elevated intrarumen pressure is associated with an increase in the frequency of primary (mixing) and secondary (eructation) contractions (more secondaries than primaries).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2907427 TI - Concentration- and pH-dependence of short-chain fatty acid absorption in the proximal and distal colon of guinea pig (Cavia porcellus). AB - 1. Absorption of short-chain fatty acids (SCFA), acetate, propionate, and butyrate was studied in simultaneously perfused proximal and distal segments of the colon in anaesthetized guinea pigs. 2. Acetate absorption rates increased linearly with concentration in both segments, indicating passive transport. 3. SCFA-clearance was independent of bulk luminal pH between pH 6.2 and 8.1 in the proximal and distal colon. SCFA-clearance was slightly higher in both segments at pH values less than 6. 4. The unexpected pH-independence of SCFA-absorption is attributed to the existence of a constant pH-microclimate at the surface of the colonic epithelium. 5. Relative permeabilities to acetate:propionate:butyrate were estimated as 1:1.19 +/- 0.03:1.27 +/- 0.05 in the proximal colon and 1:2.31 +/- 0.39:3.50 +/- 0.61 in the distal colon. The significance of these findings with respect to the pH-partition hypothesis are discussed. PMID- 2907428 TI - Hormonal control of lipolysis from the white adipose tissue of hibernating jerboa (Jaculus orientalis). AB - 1. Plasma glucose, glycerol, free fatty acids and total lipid content of the white adipose tissue were measured in euthermic and hibernating jerboa. 2. During hibernation, plasma glucose and glycerol were low compared to the euthermic animals, whereas there was no obvious difference in plasma free fatty acids. The white adipose tissue lipid content was strongly reduced in the hibernating state. 3. The effect of lipolytic hormones (norepinephrine and glucagon) and antilipolytic hormone (insulin) on in vitro glycerol release by adipose tissue isolated from hibernating or euthermic jerboa has been studied. 4. The white adipose tissue from hibernating jerboa presented a higher sensitivity to norepinephrine and glucagon than that of euthermic jerboa; insulin did not modify either basal glycerol release or lipolysis induced by the two lipolytic hormones at low temperatures (7 degrees C) and during the rewarming (from 7 degrees C to 37 degrees C) of the tissue slices. 5. These results suggested that white adipose tissue constitutes an important source of substrates derived from lipolysis during hibernation. PMID- 2907429 TI - The effects of fasting on some physiological parameters in the meadow vole, Microtus pennsylvanicus. AB - 1. The effect of fasting on respiratory quotient (RQ), metabolic rate, blood glucose, liver glycogen, carcass lipids, interscapular brown adipose tissue (IBAT), and body temperature was investigated in Microtus pennsylvanicus. 2. The utilization of carbohydrates during fasting leads to a severe hypoglycemia within 6 hr. 3. The hypoglycemia does not seem to stem from the inability to mobilize glycogen or fat reserves. 4. The hypoglycemic state may be responsible for the decreased SMR and body temperature. 5. The predominant use of carbohydrates may stem from a high metabolic rate coupled with a low calorie diet which forces the voles to feed frequently. PMID- 2907430 TI - Binding sites for atrial natriuretic peptide in the kidney and aorta of the hagfish (Myxine glutinosa). AB - 1. In the atlantic hagfish (Myxine glutinosa) binding sites for atrial natriuretic peptide (ANP) were visualized by autoradiography in contractile structures of the renal system (glomeruli, neck segment, and archinephric duct) and in the aorta. 2. Since the location of binding sites is comparable to that in higher vertebrates including man, these results suggest that ANP may act as a hormone already in cylcostomata. PMID- 2907431 TI - Creatinine and inulin clearance at the different nitrogen and energy intake in sheep. AB - 1. Renal creatinine and inulin clearances were compared between sheep fed (a) high nitrogen and high energy diet; (b) low nitrogen and high energy diet and (c) low nitrogen and low energy diet. 2. Inulin clearance was significantly lower in sheep on both low nitrogen diets vs the group with high nitrogen intake. Differences were not ascertained between the groups on low nitrogen diets. 3. No significant differences were found in the creatinine clearance. The creatinine inulin clearance ratio was higher when animals were fed low nitrogen diets, vs the group on a high nitrogen diet. 4. Results suggest that the endogenous creatinine is not suitable for the GFR measurement in sheep under the different conditions of nutrition. PMID- 2907432 TI - Thyroxin specifically stimulates anuran larvae epidermal sodium pump during metamorphosis. AB - 1. Sodium pump, measured as K+-dependent, ouabain sensitive pNPPase, but not the non-specific, ouabain insensitive pNPPase, was stimulated by thyroxin in epidermis of tadpoles of Rana perezi. 2. Epidermal K+-pNPPase of thyroxin treated tadpoles was only stimulated in those stages already showing activity and reached levels similar to adult frogs in tadpoles at metamorphic climax. PMID- 2907433 TI - Sympatho-adrenal activity and metabolic responses in fasted rats--the role of interscapular brown adipose tissue. AB - 1. Sympatho-adrenal (SA) and metabolic responses to fasting were studied in sham operated (SHAM) rats and in those with interscapular brown adipose tissue (IBAT) removed. 2. Fasting significantly increased adrenaline (A) excretion and serum free fatty acids (FFA), but decreased noradrenaline (NA) excretion and blood glucose level in SHAM rats. 3. IBAT removal did not change metabolic responses while it markedly altered the SA activity. Fasting in animals void of IBAT potentiated the activity of adrenal medulla, inhibited the FFA rise and prevented glucose reduction, which is normally observed in SHAM-fasted rats. 4. Results suggest the significance of IBAT in the regulation of the blood level of energy substrates in fasted rats and in maintaining the basal level of NA excretion. PMID- 2907434 TI - Tissue levels of bilirubin and biliverdin in the sea lamprey, Petromyzon marinus L., before and after biliary atresia. AB - 1. Liver, intestine, kidney, muscle and epidermis from larvae, juvenile adults and upstream migrants of the sea lamprey, Petromyzon marinus L., were assayed for the presence of biliverdin and bilirubin. Urine was also examined for these bile pigments in juveniles and upstream migrants. 2. Bilirubin concentration increased dramatically in the liver and caudal intestine following loss of larval bile ducts while biliverdin levels were highest in the liver of upstream migrants and rose sharply in the caudal intestine immediately following the atresia. 3. Small amounts of bile pigment were present in larval kidneys but high concentrations were found in this organ in upstream migrants. The urine of the latter possessed biliverdin. 4. Mucus of the epidermis may be a vehicle for transport and release of bilirubin in upstream migrants. 5. These data indicate that lampreys utilize different avenues for bile pigment storage and elimination over the course of their life cycle. PMID- 2907435 TI - Comparative water economy of sympatric rodents in a Chilean semi-arid habitat. AB - 1. Water requirements, water balance components and dependence on exogenous water were estimated in four species of sympatric rodents inhabiting a Chilean semi arid region. 2. A significant increase in free water drinking was observed in all rodents when the diet composition was changed from 14 to 20% protein. 3. Under water balance conditions the cricetid species (Phyllotis darwini, Oryzomys longicaudatus and Akodon olivaceus) showed 1.66 to 1.88 times the weight-specific daily water gain of Octodon degus. 4. In the three cricetid rodents, evaporation was the largest water loss component (2/3 to 3/4 of total loss), while in O. degus evaporative water loss amounted to only 38% of the total. 5. Survival time during water deprivation ranged from 13.4 days in O. degus to only 4 days in O. longicaudatus. 6. All water variables combined indicate that water dependence of O. longicaudatus greater than P. darwini greater than A. olivaceus greater than O. degus. PMID- 2907436 TI - Electrophysiology of newt skin: responses to salt-depletion, aldosterone, arginine vasotocin and epinephrine. AB - 1. Newts (Taricha granulosa), salt-depleted by 3 weeks' immersion in distilled water, showed significantly higher in vitro integumental short-circuit current (SCC) than control newts immersed in dilute saline. 2. Isolated, in vitro preparations of newt skin responded to aldosterone (10(-6) M), arginine vasotocin (10(-9)-10(-8) M), and epinephrine (10(-7)-10(-5) M) by increasing SCC. 3. The hormonal response of the skin of this salamandrid urodele, as judged from in vitro (Ussing chamber) measurements, is similar to that seen in classical anuran ("frog skin") preparations. PMID- 2907437 TI - Apomorphine-induced vomiting in rainbow trout (Salmo gairdneri). AB - 1. The LD50 for a 7-day period following intraperitoneal injection of apomorphine HCl was calculated to be 158 mg/kg in rainbow trout. 2. Intraperitoneal injection of apomorphine at doses of 60 mg/kg or greater caused vomiting of plastic balls which had been placed in the stomachs of rainbow trout. 3. Apomorphine-induced effects included vomiting, vomiting behavior, toxicity, increased respiration, impaired motor control and equilibrium, and increased aggression. 4. The vomiting control mechanism of trout may be similar to that described in mammals. PMID- 2907438 TI - Plasma arginine vasotocin and angiotensin II in the water deprived Kelp gull (Larus dominicanus), Cape gannet (Sula capensis) and Jackass penguin (Spheniscus demersus). AB - 1. The basal levels of the osmoregulatory hormones, arginine vasotocin (AVT) and angiotensin II (AII) were measured (by radioimmunoassay) in the plasma of conscious Kelp gulls, Cape gannets and Jackass penguins. 2. The responses of the hormones to similar degrees of hypertonicity and hypovolemia caused by water deprivation have also been determined. 3. Dehydration elevated plasma AVT and plasma AII in all three species. 4. The AVT concentration was increased by 2-4 fold and although in each case the correlation between plasma osmolality and plasma AVT was highly significant (2P less than 0.01), the sensitivity of release was greater in the gull (1.13 pg/ml per mOsm/kg) than in the gannet (0.36 pg/ml per mOsm/kg) or penguin (0.44 pg/ml per mOsm/kg). 5. Dehydration increased plasma AII 3-fold in the three bird types. PMID- 2907439 TI - Phylogenetic study of the oxytocin-like immunoreactive system in invertebrates. AB - 1. A phylogenetic study of oxytocin (OXT)-like immunoreactive cells was performed by the PAP method in the central nervous system of invertebrates. 2. The immunoreactivity was detected in the nerve cells of Hydra magnipapillata of the Coelenterata; Neanthes japonica and Pheretima communissima of the Annelida; Oncidium verrucosum, Limax marginatus and Meretrix lamarckii of the Mollusca; and Baratha brassica of the Arthropoda. 3. No immunoreactive cells were found in Bipalium sp. of the Platyhelminthes; Pomacea canaliculata, Aplysia kurodai, Bradybaena similaris and Achatina fulica of the Mollusca; and Gnorimosphaeroma rayi, Procambarus clarkii, Hemigrapsus sanguineus, Helice tridens and Gryllus bimaculatus of the Arthropoda; Asterina pectinifera of the Echinodermata; and Halocynthia roretzi of the Protochordata. 4. These results demonstrate that an OXT-immunoreactive substance is widely present not only in vertebrates but also in invertebrates. 5. OXT seems to have been introduced into these invertebrates at an early stage of their phylogenetic history. PMID- 2907441 TI - Effects of a high concentration of CO2 on electrocardiograms in the carp, Cyprinus carpio. AB - 1. The effects of a high concentration of CO2 (PCO2 = 250 mmHg and PO2 = 360 mmHg in water) and MS222 (tricaine methanesulfonate, 1/8000 or 1/5000) on the electrocardiogram (ECG) in carp were examined using five kinds of bipolar leads from the body surface. 2. In the carp anesthetized with the high concentration of CO2 for 30 min, the QRS duration, PQ interval and and direction of the QRS axis on the frontal plane significantly changed. Even after recovery from anesthesia, delay in the QRS duration was still recognized. 3. The concentration of CO2 used in this study had an anesthetic action to the same degree as 1/8000 of MS222 and had a much more severe effect on the ECG of the carp than 1/5000 of MS222. PMID- 2907440 TI - Phylogenetic study of the arginine-vasotocin/arginine-vasopressin-like immunoreactive system in invertebrates. AB - 1. A phylogenetic study of arg-vasotocin (AVT)/arg-vasopressin (AVP)-like immunoreactive cells was performed by the PAP method in the central nervous system of invertebrates. 2. The immunoreactivity was detected in the nerve cells of Hydra magnipapillata of the Coelenterata; Neanthes japonica and Pheretima communissima of the Annelida; Pomacea canaliculata, Aplysia kurodai, Oncidium verrucosum, Bradybaena similaris, Achatina fulica, Limax marginatus and Meretrix lamarckii of the Mollusca; Gnorimosphaeroma rayi, Hemigrapsus sanguineus, Gryllus bimaculatus and Baratha brassicae of the Arthropoda; Asterina pectinifera of the Echinodermata; and Halocynthia roretzi of the Protochordata. 3. No immunoreactivity was detected in Bipalium sp. of the Platyhelminthes, or in Procambarus clarkii and Helice tridens of the Arthropoda. 4. From these results, it appears that AVT/AVP is a phylogenetically ancient peptide which is present in a wide variety of invertebrates. 5. The actions of AVT/AVP and its presence in invertebrates are discussed. PMID- 2907442 TI - Electrocardiograms in five bipolar leads recorded from the body surface of three fish species (Cyprinus carpio, Oreochromis niloticus and Pagrus major) in fresh or sea-water. AB - 1. ECGs were recorded using five bipolar leads from the body surface of porgy Pagrus major and tilapia Oreochromis niloticus in fresh or sea-water, or held on a dry towel. 2. The maximum QRS amplitude was detected in lead V in both species being 54 +/- 25 microV in porgy and 241 +/- 78 microV in tilapia, respectively, when the fish were held on the dry towel. 3. Clear ECG waves could not be obtained from porgy in sea-water because of the porgy's small cardiac potential and leakage of the potential. However, clear ECG waves could be obtained in sea water from the body surface of tilapia, with the average QRS amplitude being 35 +/- 8 microV. 4. The mean electrical P and QRS axes in tilapia were directed toward almost the same direction (frontal downward), whereas both P and QRS axes in most carp were in opposite directions. In porgy, the relationship between the P and QRS axes could not be identified due to the smaller amplitude of the P wave. PMID- 2907443 TI - Energy cost of whole-body protein synthesis measured in vivo in chicks. AB - 1. Energy cost of whole-body protein synthesis was measured in vivo in chicks by comparing the changes in protein synthesis and heat production after the administration of cycloheximide, an inhibitor of protein synthesis. 2. Incorporation of phenylalanine into whole-body protein fraction was promptly inhibited after the intravenous injection of cycloheximide, and the effect was sustained for at least 3 hr. 3. Both whole-body protein synthesis and total heat production were significantly reduced by the cycloheximide administration. 4. The energy cost of whole-body protein synthesis was calculated to be 5.35 kJ per g protein synthesis, and hence on a molar basis 7.52 ATPs are required per peptide bond synthesis. PMID- 2907444 TI - An improved electrode design for en passant recording from small nerves. AB - 1. A modification of the oil and hook electrode technique for recording extracellularly from fine nerves is described. 2. It uses a fine hook and a plastic tube that can be manipulated independently, and through which a high viscosity oil or grease may be forced over the nerve. 3. The suitability of the electrode for high-quality and long-term recording is discussed. PMID- 2907445 TI - Circulating levels of biotin in the fowl (Gallus domesticus): modulation by oestrogen. AB - 1. Exogenous oestrogen administration to immature male and female chickens significantly increased plasma biotin and significantly reduced liver biotin concentrations. 2. The elevation in plasma biotin concentrations was dose dependent and maximum values were observed 48 hr after a single injection of oestrogen. 3. A second oestrogen injection significantly increased plasma biotin concentrations compared with values obtained after the initial injection given 10 days previously. 4. Plasma biotin concentrations were significantly increased in female, but not male, birds approaching sexual maturity. This increase coincided with the time of the known surge in endogenous oestrogen production by the developing ovary. PMID- 2907447 TI - Urinary excretion of free glucocorticosteroids and testosterone in the Mongolian gerbil (Meriones unguiculatus): effects of long-acting corticotrophin and human gonadotrophin. AB - 1. Methods for the quantitative collection of 24-hr urines of small laboratory animals and for the measurement of urinary free glucocorticosteroids and testosterone are described. 2. Urinary glucocorticosteroids and testosterone were determined in 0.1-0.5 ml-aliquots of 1/100 diluted urines after kieselgur mini column extraction. 3. Excretion of glucocorticosteroids and testosterone in undisturbed Mongolian gerbils was 329 and 13 ng/day, respectively. 4. Administration of long-acting (1-24)ACTH (20 IU/animal) increased glucocorticosteroid and testosterone excretion to about 2000 ng/day (glucocorticosteroids) and to about 30 ng/day (testosterone) over 3 days. 5. In animals injected with 100 IU/animal HCG, testosterone excretion was elevated to about 35-50 ng/day over 3 days. 6. As the results show, the measurement of urinary excretion of free glucocorticosteroids and testosterone is a reliable index of adrenal-gonadal function in the Mongolian gerbil. 7. Furthermore, in small laboratory animals, steroid measurements in 24-hr urines may be superior to determinations in plasma, since amounts of urinary steroid are relatively high and 24-hr urines can be collected over longer time periods without stressing the animals. PMID- 2907446 TI - Basolateral amino acid and glucose transport by the intestine of the teleost, Anguilla anguilla. AB - 1. D-glucose transport into BLMV was osmotically reactive, sodium independent, and inhibited by phloretin but not by phloridzin. 2. The survey of 6 L-amino acids identified three groups with respect to transfer across the basolateral cell border. Transport of proline and glutamate occurred by Na-dependent carriers and by apparent simple diffusion. Alanine, lysine and phenylalanine were transported by Na-independent carriers and apparent simple diffusion. Glycine transport was stimulated above apparent simple diffusion only by a simultaneous inwardly-directed Na gradient and outwardly-directed K gradient. 3. Only proline and glutamate demonstrated the ability to depolarize the membrane potential, consistent with Na-dependent rheogenic transport. PMID- 2907449 TI - Changes in the metabolic profile of the equine gluteus medius as a function of sampling depth. AB - 1. Cross sections from the middle of the gluteus medius were removed from 10 adult horses and used to evaluate changes in histochemically determined muscle fiber type and biochemically determined metabolic enzyme activities as a function of sample depth. 2. Muscle fiber types determined using histochemical methods for myosin ATPase (pH 9.4) and succinic dehydrogenase (SDH) activity indicated percent fast-twitch glycolytic (FG) muscle fibers decreased and slow-twitch oxidative (SO) fibers increased as a function of increasing sampling depth. 3. Percent histochemically determined fast-twitch oxidative glycolytic (FOG) fibers decreased slightly only in the deepest region of the gluteus medius. 4. Citrate synthase (CS) enzymatic activity, used as a marker for mitochondrial oxidative potential, increased 2.5-fold in activity per g of muscle protein from 1 to 8 cm sampling depth. 5. 3-hydroxyacyl-CoA dehydrogenase (HAD) enzymatic activity, used as a marker for lipid oxidation potential, increased 3-fold in activity per g of muscle protein when the depth increased from 1 to 8 cm. 6. Phosphorylase (PS) enzymatic activity, used as a marker for potential glycogen utilization, decreased 50% in activity per g of muscle protein when going from 1 to 8 cm. 7. Lactate dehydrogenase (LDH) enzymatic activity, used as a marker for anaerobic glycolytic potential, decreased about 50% in activity as the sampling depth increased from 1 to 8 cm. 8. In summary, the superficial portion of the equine gluteus medius was found to be more glycolytic and less aerobic in its metabolic profile than deeper regions. The muscle became progressively more aerobic and less glycolytic with increasing sampling depth. PMID- 2907448 TI - Pressor and hemodilution responses compensate for acute hemorrhage in bluefish. AB - 1. After hemorrhage of 21% blood volume (0.9% body weight) blood pressure (BP) and heart rate (H.R.) of unanesthetized bluefish (Pomatomus saltatrix) recovered within 5 min. 2. Phentolamine blocked this recovery. 3. Atropine increased control H.R. from 48 to 87 per min, and to 108 after hemorrhage, with delay of BP recovery to 10 min. 4. With small, repeated hemorrhages every 20 min, hemodilution and recovery of BP occurred between hemorrhages. Removal of 27% blood volume resulted in only temporary recovery. 5. Thirty min after hemorrhage, plasma epinephrine was 5 x and norepinephrine 8 x control. 6. Thus, bluefish tolerate hemorrhage with initial vasoconstriction via alpha-adrenergic pathways, and hemodilution. PMID- 2907450 TI - The effect of oral L-carnitine supplementation on the muscle and plasma concentrations in the Thoroughbred horse. AB - 1. L-carnitine was administered orally to thoroughbred horses for 58 days. 2. Acceptability and effects on plasma, muscle and urine concentration were studied. 3. Ten-60 g/day (as 2-3 doses) was acceptable with no deleterious effects. 4. One x 10 g L-carnitine significantly raised the plasma-free carnitine concentration (7 hr post) from 21.2 to 31.8 mumol/l; 2 x 30 g increased the mean to 36.5 mumol/l. 5. Plasma acetylcarnitine increased from approximately 1 to 5.5 mumol/l (7 hr post) on 2 x 30 g/day. 6. Muscle total carnitine was unchanged over 58 days. 7. Urinary output accounted for 3.5-7.5% of added carnitine, indicating low intestinal absorption. PMID- 2907451 TI - Cation movement in rat articular and non-articular cartilage and in isolated chondrocytes: calcium influx and efflux. AB - 1. Calcium ion influx varies between different types of young adult rat cartilage. Sternal cartilage accumulates significantly less Ca2+ than other cartilage types. 2. Influxes of Ca2+ into young adult and ageing tibial cartilage display no significant differences. 3. Efflux of Ca2+ from sternal and tibial cartilage resolves into exponential phases indicative of three compartments. Tracheal cartilage displays two compartment behaviour only. 4. Efflux of Ca2+ from isolated chondrocytes has different characteristics to cartilage efflux with the third slow compartment reduced. 5. Modification of Ca2+ efflux by lanthanum and barium is suggestive of an exchange of strongly bound extracellular calcium during the slow phase of the efflux from young adult tibial cartilage. 6. The metabolic inhibitor 2,4-dinitrophenol is without effect on the efflux of Ca2+ from tibial articular cartilage. 7. The degree of calcium binding exhibited during efflux depends upon cartilage type. Non-articular sternal cartilage binds calcium more strongly than articular tibial, both binding more strongly than non articular tracheal cartilage. 8. In articular cartilage calcium binding shows an age-related increase. PMID- 2907452 TI - Chemotherapy of experimental (murine) Clostridium perfringens type A gas gangrene. AB - Five antimicrobial drugs (ciprofloxacin, clindamycin, imipenem, penicillin G, and rifampin) were examined for therapeutic efficacy in a murine model gas gangrene due to Clostridium perfringens type A, following infection with large bacterial inocula. Imipenem was effective against all 6 strains of C. perfringens; conversely, penicillin G failed against these 6 strains. Ciprofloxacin, clindamycin, and rifampin occupied intermediate positions. PMID- 2907453 TI - Effects of pretreatment with the retinoid N-(4-hydroxyphenyl)-all-trans retinamide and phenobarbital on the disposition and metabolism of N-(4 hydroxyphenyl)-all-trans-retinamide in mice. AB - The effects of pretreatment with N-(4-hydroxyphenyl)-all-trans-retinamide (4-HPR) and phenobarbital (PB) on the distribution and metabolism of 4-HPR, and on the levels of hepatic cytochromes, were investigated in female BDF mice. Pretreatment of mice for 3 days with 10 mg/kg 4-HPR had no effect on the disposition of 4-HPR in the serum, liver, mammary gland, or urinary bladder. 4-HPR pretreatment also had no effect on the pharmacokinetics of any of its metabolites in the liver, or on the levels of hepatic cytochromes P450 or b5. By contrast, pretreatment of mice for 3 days with 80 mg/kg PB had a significant effect on the disposition of 4 HPR in all the tissues examined; the areas under the concentration-time curves for PB-pretreated mice were half those for vehicle-pretreated mice. PB pretreatment also significantly reduced the levels of four metabolites of 4-HPR in the liver and increased the levels of hepatic cytochromes P450 and b5. These data suggest that prior or concomitant administration of drugs that induce the mixed function oxidase system could result in changes in retinoid disposition and metabolism; such changes may alter retinoid chemopreventive activity. PMID- 2907454 TI - Renal transepithelial transport of nucleosides. AB - Previous work from this and other laboratories has suggested that the mammalian kidney has unique mechanisms for handling purine nucleosides. For example, in humans and in mice, adenosine undergoes net renal reabsorption whereas deoxyadenosine is secreted [Kuttesch and Nelson: Cancer Chemother. Pharmacol. 8, 221 (1982)]. The relationships between these renal transport systems and classical renal organic cation and anion, carbohydrate, and cell membrane nucleoside transport carriers are not established. To investigate possible relationships between such carriers, we have tested effects of selected classical transport inhibitors on the renal clearances of adenosine, deoxyadenosine, 5' deoxy-5-fluorouridine (5'-dFUR), and 5-fluorouracil in mice. The secretion of deoxyadenosine and 5'-dFUR, but not the reabsorption of adenosine or 5 fluorouracil, was prevented by the classical nucleoside transport inhibitors, dipyridamole and nitrobenzylthioinosine. Cimetidine, an inhibitor of the organic cation secretory system, also inhibited the secretion of 5'-dFUR, although it did not inhibit deoxyadenosine secretion in earlier studies [Nelson et al.: Biochem. Pharmacol. 32, 2323 (1983)]. The specific inhibitor of glucose renal reabsorption, phloridzin, failed to inhibit the reabsorption of adenosine or the secretion of deoxyadenosine. Failure of the nucleoside transport inhibitors and phloridzin to prevent adenosine reabsorption suggests that adenosine reabsorption may occur via a unique process. On the other hand, inhibition of the net secretion of deoxyadenosine and 5'-dFUR by dipyridamole and nitrobenzylthioinosine implies a role for the carrier that is sensitive to these compounds in the renal secretion (active transport) of these nucleosides. PMID- 2907455 TI - Identification of ibopamine metabolites in rat and dog urine. AB - Metabolism of ibopamine (N-methyldopamine-O,O'-diisobutyryl ester) was studied in rats and dogs. The compound was well absorbed in both species when given orally. Most of the administered radiolabel (74-94%) was excreted within 24 hr in urine of both species. The major metabolite in rat urine was 4-glucuronylepinine (63% of the total administered dose). Minor metabolites identified were 4-O-glucuronyl 3-O-methylepinine, 3,4-dihydroxyphenylacetic acid (DOPAC), DOPAC-glucuronide, homovanillic acid (HVA), and HVA-glucuronide. Free epinine and epinine sulfate were detected in the range of less than 1% of the total administered dose. Metabolite patterns in dog urine were different from those of rat urine. The major metabolite was epinine-3-O-sulfate (62% of the total administered dose). Minor metabolites identified in dog urine were DOPAC-sulfate, HVA-sulfate, and free HVA. Free epinine was detected but in the range of less than 1% of the total administered dose. These results showed that ibopamine underwent extensive hydrolysis in vivo to epinine, which was subsequently conjugated and excreted as major metabolites in urine. In addition, side chain degradation of epinine led to minor metabolites, which were excreted in urine as free and conjugated forms. The route of conjugation of ibopamine metabolites is species dependent. PMID- 2907456 TI - In vivo rat hemoglobin thiyl free radical formation following administration of phenylhydrazine and hydrazine-based drugs. AB - We have employed the ESR spin trapping technique in vivo to detect the formation of the 5,5-dimethyl-1-pyrroline N-oxide (DMPO)/hemoglobin thiyl free radical adduct in the blood of rats following administration of hydrazine-based drugs. The drugs examined were isoniazid, iproniazid, phenelzine, and hydralazine. In addition, phenylhydrazine and acetylhydrazine were also studied in a like manner. Of the four drugs, only phenelzine and iproniazid were able to induce the formation of the DMPO/hemoglobin thiyl free radical adduct in vivo, whereas only phenelzine and hydralazine were able to form this adduct in vitro. We were able to decrease the in vivo iproniazid-induced adduct formation by pretreating the rats with bis-para-nitrophenylphosphate, an arylamidase inhibitor. Our results support the idea that iproniazid is hydrolyzed in the liver to a more reactive metabolite, most likely isopropylhydrazine, which is subsequently released into the blood stream. In addition to the drug studies, experiments were performed to provide additional evidence that the radical adduct we detected was indeed of a hemoglobin thiyl free radical. Studies employing alpha-phenyl-N-t-butylnitrone (PBN) as the spin trap in place of DMPO also showed the formation of the PBN/hemoglobin thiyl free radical adduct. PMID- 2907457 TI - Virginiamycin metabolism in cattle rumen fluid. AB - The antibiotic virginiamycin (VM) was extensively metabolized in cattle rumen fluid in vitro. The antimicrobial activity of VM decreased rapidly with an initial half-life of approximately 8 hr. In contrast, in buffer at near neutral pH, VM maintained its full activity for at least 24 hr. Four metabolites were isolated and identified using a combination of spectral techniques including FAB MS-MS, LC-MS, and 500 MHz NMR. The metabolites were all derived from reduction of the major component of virginiamycin, factor M. The minor component, factor S, was not metabolized in cattle rumen fluid. The metabolic pathways involved included C = C and C = O reduction as well as dehydroxylation. All metabolites were found to have less antimicrobial activity than the parent factor M. In addition to the metabolites, two factor M decomposition products were isolated after incubation of VM in buffer alone. These two products resulted from the dehydration of factor M and were shown to interconvert at room temperature. PMID- 2907458 TI - In vivo radical trapping and biliary secretion of radical adducts of carbon tetrachloride-derived free radical metabolites. AB - Products of the well documented reductive metabolism of CCl4 to .CCl3 have been examined by free radical trapping and ESR in vivo. We have found the phenyl-N-t butylnitrone (PBN) radical adduct of .CCl3 in the bile of rats treated with the radical trap and 13CCl4. Hypoxia or pretreatment with phenobarbital has been reported to enhance the hepatotoxicity of CCl4 in vivo; these treatments also produced an increase in the biliary concentration of the PBN/.CCl3 radical adduct and in the .CCl3-derived PBN/.CO(-)2 radical adduct as well. A 13C-invariant spectrum detected upon PBN administration, with or without carbon tetrachloride, may be due to a lipid-derived species. ESR analysis of bile from animals treated with free radical traps and xenobiotics may prove useful in monitoring hepatic free radical-adduct formation in vivo. PMID- 2907459 TI - O-dephenylation and conjugation with benzoylornithine. New metabolic pathways for 3-phenoxybenzoic acid in chickens. AB - Metabolism of [benzyl-14C]fluvalinate by chickens produces 3-phenoxybenzoic acid, which is further degraded by two new pathways. The first pathway involves O dephenylation, not reported previously for related pyrethroids in birds or mammals. O-Dephenylation is a major metabolic route (12% of the applied 14C). In the second pathway, 2% of the applied dose is converted into four conjugates of benzoylornithine (two with 3-hydroxybenzoic and two with 3-phenoxybenzoic acids). The predominant conjugate with benzoylornithine is N2-(3-hydroxybenzoyl)-N5 benzoylornithine. PMID- 2907460 TI - Sexual dimorphism of nicotine metabolism and distribution in the rat. Studies in vivo and in vitro. AB - Interpretation of sex differences in nicotine metabolism and disposition in rats required studies both in vivo and in vitro to provide both metabolic and pharmacokinetic data. In each of four rat strains studied in vitro, males metabolized nicotine faster than did females. In Sprague-Dawley rats, studies of nicotine kinetics after a single iv dose of [14C]nicotine revealed a larger nicotine volume of distribution in females than in males. A prolonged plasma nicotine half-life in females balanced the larger volume of distribution, so that no sex difference appeared in plasma clearance of nicotine. Nevertheless, sex differences in nicotine metabolism are indicated inasmuch as 1) females had lower plasma cotinine concentrations than did males; 2) urinary recoveries of nicotine were higher in female than in male rats; 3) total urinary output of nicotine metabolites was higher in male than female rats, consistent with the enhanced N- and C-oxidation of nicotine by male rats observed in vitro. In female rats the reduced rate of nicotine metabolism, as well as a larger volume of distribution of nicotine, explains in part the reported increased lethality of female compared with male rats. PMID- 2907461 TI - Renal handling of 5-nitrofuran nephrotoxins in the rat. AB - Formic acid 2-[4-(5-nitro-2-furyl)-2-thiazolyl)-hydrazide (FNT) and 3 hydroxymethyl-1-([3-(5-nitro-2-furyl)-allydidene]amino)hydantoin (HMN) were investigated to determine whether differences in the renal handling of these two chemicals might provide evidence to explain their different patterns of toxicity and carcinogenicity. The isolated perfused rat kidney and whole animal were used. In the isolated perfused rat kidney, both FNT and HMN had similar half-lives (t1/2) but the urinary excretion and renal clearance of HMN (2.1 +/- 0.4 greater than those of FNT (0.2 +/- 0.1 nmol/min and 0.06 +/- 0.01 ml/min, respectively). Probenecid increased the t1/2 and decreased the metabolic clearance of HMN but did not have any effect on FNT t1/2 or clearance. These differences in excretion of FNT and HMN could not be explained on the basis of protein binding. The total clearances of FNT and HMN were similar and significantly higher than that of the 5-nitrofuran bladder carcinogen ANFT. In the whole animal, the urinary excretion of HMN was about 10-fold greater than that of FNT. The t1/2 of both FNT and HMN was less than 5 min in the whole animal. Probenecid decreased the urinary excretion of HMN from 9.7 +/- 1.4% to 4.4 +/- 1.0% (p less than 0.05). Compared with HMN, FNT has less urinary excretion but a similar elimination t1/2, suggesting a greater nonrenal clearance. HMN but not FNT has tubular excretion. Thus, alterations in substituents of 5-nitrofurans markedly alter their renal handling and may partially explain their diverse toxic effects. PMID- 2907462 TI - Regiochemistry and enantioselectivity in the oxidative N-dealkylation of verapamil. AB - The oxidative N-dealkylation of verapamil (1), a calcium channel antagonist, was examined in the presence of rat and human liver microsomes by using GC-MS methodology and synthesized regio-isomeric standards. All three possible secondary amine metabolites, N-methyl-4-(3,4-dimethoxyphenyl)-4-cyano-5 methylhexylamine (5), norverapamil (4), and N-methyl-2-(3,4 dimethoxyphenyl)ethylamine (3), were formed as microsomal metabolites. Compound 5 and norverapamil (4) were major products. Substrate stereoselectivity for the N dealkylation process was determined when pseudoracemic verapamil[equimolar (S)-( )-verapamil-d6 and (R)-(+):verapamil-d0] was used as substrate. In the presence of rat liver microsomes, a slight enantiomeric preference for the metabolism of (R)-verapamil to secondary amines 3 and 5 (S/R ratio = 0.88 and 0.78, respectively) was observed. In contrast, (S)-verapamil was preferentially metabolized to norverapamil (4) and primary amine 9 (S/R ratio = 1.20 for both). The enantioselectivity for the N-dealkylation process in the presence of human liver microsomes was slight and variable (six samples). Quantitatively, the major N-dealkylation routes in both microsomal systems yielded norverapamil (4) and secondary amine 5. Greater substrate enantioselectivity was observed for the N dealkylation process in rat liver microsomes than in human liver microsomes. In rat liver microsomal studies, two aliphatic aldehydes (2 and 6) were successfully trapped as their O-methyloximes (7 and 11, respectively) by using methoxylamine. In addition, the alcohols formed from reduction of these aldehydes were observed, due in part to a direct reduction by NADPH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2907463 TI - Bioavailability of benzo(a)pyrene deposited in the lung. Correlation with dissolution from urban air particulates and covalently bound DNA adducts. AB - Dissolution kinetics of benzo(a)pyrene (B(a)P associated with urban air particulates were investigated in vitro and related to availability of the carcinogen in the isolated, perfused, and ventilated rat lung. Calculations of bioavailability and mean dissolution time in the lung produced results in concordance with experimental data. By convolution calculation, with in vitro desorption as input function and the disposition of B(a)P dosed intratracheally to the lung in an alveolar surfactant solution as reference, hypothetical areas under B(a)P buffer concentration vs. time curves (AUC) were calculated. AUC value for 1.5 micrograms of microcrystalline (MCr) B(a)P was 16 +/- 2 pmol/ml/min (N = 6), which was identical with the corresponding experimental value of 16 +/- 5 pmol/ml/min (N = 6), from lung perfusion experiments. For B(a)P adsorbed to urban air particulates (UAP-1), predicted and experimental AUC values did amount to 7 +/- 2 (N = 5) and 10 +/- 4 (N = 5) pmol/ml/min, respectively. Absolute bioavailability was calculated by deconvolution to 87% for B(a)P in alveolar surfactant. In vitro dissolution of B(a)P from urban air particulates (UAP-1 to 4) revealed a wide variation in desorption characteristics for different particulate samples. Dissolution parameters determined in vitro were positively related to mean absorption time and mean dissolution time in the lung, using three different preparations. The precision in predictions of availability of B(a)P from in vitro desorption rates, with MCr and UAP-1 representing the greatest differences observed, supports the hypothesis that desorption is the rate-limiting step during uptake of B(a)P in the lung.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2907464 TI - Pharmacokinetics and enterohepatic circulation of 2-n-propyl-4-pentenoic acid in the rat. AB - The pharmacokinetics of 4-ene-valproic acid (4-ene-VPA), a putative hepatotoxic metabolite of the anticonvulsant valproic acid (VPA), were studied in normal and bile-exteriorized rats. A single iv bolus dose of 20 or 100 mg/kg of 4-ene-VPA was administered to each rat. Plasma decline of 4-ene-VPA was apparently monoexponential at the low dose and nonlinear at the high dose. In normal rats, 4 ene-VPA was recycled in the plasma due to enterohepatic circulation (EHC). A time lag pharmacokinetic model was used to describe the plasma profile, including the appearance of a secondary plasma peak, in normal animals receiving the low dose of 4-ene-VPA. Total apparent plasma clearance was 8.67 ml/min.kg at the low dose and 5.89 ml/min.kg at the high dose. EHC was abolished in bile-exteriorized animals. In these rats, the apparent plasma elimination half-life increased from 12.7 to 18.8 min and plasma clearance decreased from 11.4 to 7.41 ml/min.kg with a 5-fold increase in the dose. 4-ene-VPA was largely eliminated in urine and bile as conjugates. In normal rats, 22% and 28% of the low and high dose, respectively, were eliminated in urine. Approximately 29% of the low dose and 21% of the high dose were recovered in bile of the rat. Like the parent drug VPA, 4 ene VPA induced dose-dependent choleresis in the rat. The pharmacokinetics of 4 ene-VPA in the rat were similar to those reported for VPA. PMID- 2907465 TI - Disposition and metabolism of letosteine in rats. AB - The metabolism and disposition of letosteine, labeled either with 14C or 35S, has been investigated in Sprague-Dawley rats. In separate experiments, rats received 20 mg/kg, iv or orally, [14C]letosteine or [35S]letosteine. Radioactivity was rapidly excreted, mainly in urine, after iv and oral administration. Recovery of radioactivity from 0-72-hr excreta averaged 95% after both routes of [14C]letosteine administration, whereas only 50% was recovered when [35S]letosteine was administered. 14CO2 accounted for about 7.3% (iv) and 5.1% (po) of the dose of [14C]letosteine. Comparison of the iv and oral areas under the plasma 14C radioactivity concentration-time curves suggested that oral absorption of letosteine was complete. Analysis of the radioactivity content of urine showed that letosteine undergoes rapid and extensive metabolism. Several metabolites were identified by TLC, HPLC, and MS. The findings are consistent with a splitting of the ester group of letosteine and subsequent cleavage of the thiazolidinyl ring, yielding cysteine, hypotaurine, taurine, and inorganic sulfate. The metabolite derived from the side chain was identified in the urine as 3-(hydroxycarbonylmethylthio)propanoic acid. It undergoes further oxidation into sulfoxide and sulfone derivatives, which are also present in the urine. PMID- 2907466 TI - Stereoselective metabolism and pharmacokinetics of disopyramide enantiomers in humans. AB - Metabolism, pharmacokinetics, and influence of alpha 1-acid glycoprotein (alpha 1 AGP) plasma levels on protein binding of (R)-(-) and (S)-(+)-disopyramide (DP) were compared, in six healthy subjects, at the steady state, after oral administration of 100 mg twice daily. The mean unbound clearance of (R)-(-)-DP and (S)-(+)-DP were 8.59 and 14.9 ml/min/kg, respectively (p = 0.003). The mean unbound renal clearance of (R)-(-)-DP and (S)-(+)-DP were 6.26 and 8.75 ml/min/kg, respectively (p = 0.025). The nonrenal clearance, i.e. hepatic metabolic clearance, of (R)-(-)-DP and (S)-(+)-DP averaged 2.32 and 6.19 ml/min/kg, respectively (p = 0.002). The mean unbound volume of distribution of (R)-(-)- and (S)-(+)-DP were 225 and 381 liters, respectively (p = 0.023). The half-life of (R)-(-)-DP and (S)-(+)-DP averaged 4.17 and 3.91 hr, respectively (p = 0.21). The mean unbound renal clearance of (R)-(-)- and (S)-(+)-mono-N dealkylated disopyramide (MND) were 3.21 and 7.02 ml/min/kg, respectively (p less than 0.001). The unbound fraction at steady state of (R)-(-)-DP and (S)-(+)-DP averaged 12.5 and 7.5%, respectively (p = 0.002). The unbound fraction at steady state of (R)-(-)-DP and (S)-(+)-MND averaged 62.6 and 60.5%, respectively (p = 0.36). The highest alpha 1-AGP plasma concentration resulted in lower unbound fraction for both DP and MND enantiomers, whereas the lowest alpha 1-AGP plasma concentration resulted in higher unbound fraction for (S)-(+)-DP only. PMID- 2907468 TI - Pharmacokinetics of the dimethylheptyl homolog of cannabidiol in dogs. AB - Cannabidiol (CBD) is one of the major nonpsychoactive cannabinoids produced by Cannabis sativa L. Recent studies have shown that a dimethylheptyl homolog (DMH) of CBD is more active as an anticonvulsant than is the naturally occurring CBD. In considering DMH as a potential antiepileptic agent, its pharmacokinetics was studied in dogs (N = 8) after both iv (20 mg) and oral (80 mg) administration. After iv administration, DMH was rapidly distributed. DMH has a mean terminal half-life of 2 hr, its plasma levels decline in a biphasic fashion, and its total body clearance is 8.3 liters/hr. This clearance value, after being normalized to blood clearance by the use of mathematical equations, was less than one half of the value of the hepatic blood flow and its extraction ratio (E) by the liver is 0.39, DMH was observed to have a mean volume of distribution of 10 liters (or 0.5 liters/kg). In four of the eight dogs studied, DMH could not be detected in the plasma after oral administration. In the other four, the oral bioavailability was 3, 21, 39, and 43%, respectively. After oral administration, DMH has a low and variable bioavailability, due to a liver first-pass effect and incomplete absorption from the gastrointestinal tract. In comparison with CBD, DMH has a shorter half-life and lower clearance and volume of distribution values, and its liver extraction ratio is about one half that of CBD. PMID- 2907467 TI - Structure-tissue distribution relationship based on physiological pharmacokinetics for NY-198, a new antimicrobial agent, and the related pyridonecarboxylic acids. AB - Comparative physiological pharmacokinetic analysis has been carried out to elucidate the different tissue distribution characteristics among eight pyridonecarboxylic acids including newly developed NY-198. The urinary and fecal recoveries of NY-198 were 76.3 +/- 1.3% and 21.0 +/- 0.1% of the dose (mean +/- SE, N = 3), respectively, after the iv administration of [14C]NY-198 as a 20 mg/kg dose. Model-independent moment analysis of the serum concentration-time profile of [14C]NY-198 gave the volume of distribution at steady state per body weight (Vdss/BW) as 1150 ml/kg. Intrinsic renal clearance (CLint.kd) and intrinsic hepatic clearance (CLint.lv) were estimated to be 7.68 ml/min/kg and 6.33 ml/min/kg, respectively, by the cumulative urinary recovery and the area under the curve of the serum concentration-time profile of NY-198 and the blood flow rate. The tissue-to-serum partition coefficients (Kp) were determined from the analysis of the tissue and serum concentration-time profiles after iv bolus or infusion of nalidixic acid, NY-198, and its structural analogue NY-239. These values were also determined from the analysis of similar data reported in the literature for the other pyridonecarboxylic acids (enoxacin, miloxacin, ofloxacin, pefloxacin, and pipemidic acid). The Kp values of NY-198 ranged from 0.22 to 4.85 and were very similar to those for ofloxacin, being the highest in the disposing organs, kidneys and liver, the lowest in fat and brain, and modest in the other nondisposing organs. A good correlation (r = 0.981) was obtained between serum unbound fraction (fp) and the steady state distribution volume per body weight (Vd(ss)/BW), which was determined from the tissue partition coefficient. Additionally, comparatively good correlations were also obtained between fp and the Kp or apparent tissue-to-serum concentration ratio (Kp,app). Thus, the difference of serum unbound fraction has been demonstrated for the determining factor of the structure-dependent tissue distribution difference, whereas the tissue binding has been suggested to be only slightly different for respective tissues among PCA derivatives. The concentration-time profile for serum and tissues (lung, heart, muscle, kidney, liver, spleen, gut, bone, skin, and brain) was predicted for NY-198 by physiological pharmacokinetics using the averaged tissue-to-serum unbound concentration ratio (Kp,f) which was determined from the Kp,f of eight PCA analogues.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2907469 TI - Mechanism for inhibitory effect of cannabidiol on microsomal testosterone oxidation in male rat liver. AB - Effects of four cannabinoids [cannabidiol (CBD), delta 8-tetrahydrocannabinol, delta 9-tetrahydrocannabinol, and cannabinol] on hepatic microsomal oxidation of testosterone (17 beta-hydroxy-androst-4-ene-3-one) were examined in adult male rats. Only CBD (30 microM) competitively inhibited 2 alpha-hydroxy-testosterone (2 alpha-OH-T) and 16 alpha-OH-T formation by hepatic microsomes but did not affect androstenedione (androst-4-ene-3,17-dione) and 7 alpha-OH-T formation. Kinetic analyses demonstrated that the inhibitory profile of CBD for testosterone oxidation was different from those of SKF 525-A, which caused competitive inhibition for 2 alpha- and 16 alpha-hydroxylations and noncompetitive inhibition for 6 alpha-hydroxylation, and of metyrapone, which inhibited only 6 beta hydroxylation competitively. CBD also suppressed formation of 2 alpha-OH-T, 16 alpha-OH-T, and androstenedione from testosterone, catalyzed by a reconstituted system containing hepatic cytochrome P-450 purified from phenobarbital-treated rats. Pretreatment of the rat with CBD (10 mg/kg, ip, once a day for 3 days) decreased testosterone oxidation at the 2 alpha-, 16 alpha-, and 17-positions and increased 7 alpha-OH-T formation, while total cytochrome P-450 content was decreased. These results suggest that CBD suppresses hepatic testosterone oxidation at the 2 alpha-, 16 alpha-, and 17-positions through selective inhibition of the male-specific cytochrome P-450 in the adult male rat. PMID- 2907470 TI - Parallel induction of plasma alpha 1-acid glycoprotein concentration and antipyrine clearance by various doses of phenobarbital in the dog. PMID- 2907471 TI - N-chenodeoxycholyl-2-fluoro-beta-alanine: a biliary metabolite of 5-fluorouracil in humans. PMID- 2907472 TI - Comparison of cyclosporine A and G pharmacokinetics. PMID- 2907473 TI - Obesity as a risk factor in drug induced organ injury. II. Increased renal cytochrome P-450 in the obese overfed rat. PMID- 2907474 TI - [Gene amplification and rearrangement of murine ribosomal RNA in virus-induced Rauscher leukemia]. AB - Using as a hybridization probe cDNA 35s RNA from the Rauscher leukemia cells, a part of rRNA gene cluster from the gene library of mice C-1 erythroleukemia cells has been cloned. Fragment 6.7 kb recloned into pUC19 rRNA was used as a probe to analyse organization of rRNA genes of mice with RL. The observed amplification and rearrangement in genome DNA of spleen cells are determined by a new type of their rRNA genes rearrangement in the nontranscribed as well as in the transcribed part of rRNA. PMID- 2907475 TI - [Effect of various beta-adrenolytic drugs and calcium channel blockers (nifedipine) on serum levels of T3 and T4 in patients with hyperthyroidism and simple goiter]. PMID- 2907476 TI - Position dependent expression of a homeobox gene transcript in relation to amphibian limb regeneration. AB - Adult urodele amphibians such as the newt Notophthalmus viridescens are capable of regenerating their limbs and tail by formation of a blastema, a growth zone of mesenchymal progenitor cells. In an attempt to identify genes implicated in specification of the regenerate, we screened a newt forelimb blastema cDNA library with homeobox probes, and isolated and sequenced clones that identify a 1.8 kb polyadenylated transcript containing a homeobox. The transcript is derived from a single gene called NvHbox 1, the newt homologue of XIHbox 1 (Xenopus), HHO.c8 (human) and Hox-6.1 (mouse). The cDNA for the 1.8 kb transcript has two exons as determined by isolation and partial sequencing of a genomic clone. The expression of the transcript shows several interesting features in relation to limb regeneration: (i) Hybridization of Northern blots of poly(A)+ RNA from limb and tail and their respective blastemas shows that the transcript in limb tissues has exons 1 and 2, whereas a 1.8 kb transcript in tail tissues has only exon 2. (ii) The transcript is expressed in limbs of adult newt but not of adult Xenopus, raising the possibility that this contributes to an explanation of the loss of regenerative ability with maturation in adult anurans. (iii) The transcript is expressed at a higher level in a proximal (mid-humerus) blastema than in a distal one (mid-radius). When distal blastemas were proximalized by treatment with retinoic acid, no change in the level of the transcript was detected by Northern analysis at a single time point after amputation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2907477 TI - DNA rearrangement of a homeobox gene in myeloid leukaemic cells. AB - A homeobox gene rearrangement has been detected in WEHI-3B mouse myeloid leukaemic cells. The rearranged gene was identified as Hox-2.4 which is a member of the Hox-2 gene cluster on mouse chromosome 11. Both the normal and the rearranged genes were cloned and analysed, and the rearranged genomic Hox-2.4 gene was sequenced. The results indicate that the rearrangement is due to insertion of an intracisternal A particle 5' upstream to Hox-2.4 and that this resulted in constitutive expression of the homeobox gene. It is suggested that constitutive expression of the homeobox gene may interrupt the normal development program in these leukaemic cells. PMID- 2907478 TI - Association of the Drosophila melanogaster engrailed protein with specific soluble nuclear protein complexes. AB - The Drosophila engrailed protein which contains a homeobox domain and specific DNA binding activity is believed to function in the regulation of gene expression during embryogenesis. Here we show that the engrailed protein interacts stably with specific complexes of soluble nuclear proteins when expressed artificially in a cell line and in the developing embryo. The engrailed complexes have molecular masses between 10(7) and 10(8) which suggests they contain a polymeric protein component. The complex is able to bind reversibly to DNA and a definitive purification shows it to be constituted of 12 distinct protein species, two of which are predominant. Purified, bacterially produced engrailed protein can be reconstituted with both culture cell and embryo nuclear protein fractions to form complexes of the same and related composition respectively. On the basis of these results we propose that protein--protein interactions as well as DNA binding are important for correct engrailed protein function in vivo. PMID- 2907479 TI - Isolation and sequence-specific DNA binding of the Antennapedia homeodomain. AB - The homeodomain encoded by the Antennapedia (Antp) gene of Drosophila was overproduced in a T7 expression vector in Escherichia coli. The corresponding polypeptide of 68 amino acids was purified to homogeneity. The homeodomain was analysed by ultracentrifugation and assayed for DNA binding. The secondary structure of the isolated homeodomain was determined by nuclear magnetic resonance spectroscopy. DNA-binding studies indicate that the isolated homeodomain binds to DNA in vitro. It selectively binds to the same sites as a longer Antp polypeptide and a full-length fushi tarazu (ftz) protein. Therefore, the homeodomain represents the DNA-binding domain of the homeotic proteins. PMID- 2907480 TI - Secondary structure determination for the Antennapedia homeodomain by nuclear magnetic resonance and evidence for a helix-turn-helix motif. AB - The homeodomain encoded by the Antennapedia (Antp) gene of Drosophila was studied in aqueous solution by nuclear magnetic resonance (NMR). Sequence-specific resonance assignments have been obtained for the complete polypeptide chain of 68 amino acid residues. The secondary structure determined from nuclear Overhauser effects (NOE) and information about slowly exchanging amide protons includes three helical segments consisting of the residues 10-21, 28-38 and 42-52, respectively. Combination of the presently available NMR data with computer modeling provided preliminary evidence for the presence of a helix-turn-helix motif in the homeodomain. Near the turn, this supersecondary structure appears to be very similar to the DNA binding site in the 434 and P22 c2 repressors, but both helices in the homeodomain include 2-3 additional residues when compared with these prokaryotic DNA-binding proteins. PMID- 2907481 TI - The WHI1+ gene of Saccharomyces cerevisiae tethers cell division to cell size and is a cyclin homolog. AB - WHI1-1 is a dominant mutation that reduces cell volume by allowing cells to commit to division at abnormally small sizes, shortening the G1 phase of the cell cycle. The gene was cloned, and dosage studies indicated that the normal gene activated commitment to division in a dose-dependent manner, and that the mutant gene had a hyperactive but qualitatively similar function. Mild over-expression of the mutant gene eliminated G1 phase, apparently entirely relaxing the normal G1 size control, but revealing hitherto cryptic controls. Sequence analysis showed that the hyperactivity of the mutant was caused by the loss of the C terminal third of the wild-type protein. This portion of the protein contained PEST regions, which may be signals for protein degradation. The WHI1 protein had sequence similarity to clam cyclin A, to sea urchin cyclin and to Schizosaccharomyces pombe cdc13, a cyclin homolog. Since cyclins are inducers of mitosis, WHI1 may be a direct regulator of commitment to division. A probable accessory function of the WHI1 activator is to assist recovery from alpha factor arrest; WHI1-1 mutant cells could not be permanently arrested by pheromone, consistent with a hyperactivation of division. PMID- 2907482 TI - Induction of vimentin synthesis in a murine myeloma cell line by TPA is strongly dependent on the composition of the cell culture medium. AB - MPC-11 mouse plasmacytoma cells virtually lacking intermediate filament (IF) proteins can be induced to synthesize and accumulate the IF protein vimentin by treatment with the tumor promoting phorbol ester 12-O-tetradecanoylphorbol-13 acetate (TPA). Like MPC-11 cells, X63-Ag8.6.5.3 mouse myeloma cells (Ag8) proved to be vimentin-negative, as assayed by immunoblotting of whole cellular protein using goat antiserum to vimentin and [125I]protein A. Vimentin synthesis could be elicited by a TPA concentration as low as 10(-9) M in cells grown in HB-102 serum free medium. Transfer of these cells to medium containing 15% fetal calf cerum (FCS) greatly reduced the ability of these cells to synthesize vimentin upon TPA treatment. After 50 generations of culture in the presence of FCS, induction of vimentin synthesis was barely detectable even at a TPA concentration of 10(-6) M. Addition of FCS to cells grown in serum-free medium partially suppressed vimentin induction by TPA. This suppression seems to be due, at least in part, to nondialyzable, heat-sensitive components of FCS, since the dialyzable fraction even enhanced vimentin induction by TPA. When cells grown in the presence of FCS were transferred back to serum-free medium, their ability to synthesize vimentin in response to TPA treatment was readily restored. The individual components of serum-free medium which proved to support vimentin induction by TPA were insulin and the unsaturated fatty acids oleic acid and linoleic acid. An even stronger TPA response could be elicited by a combination of these components.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2907483 TI - Heavy water (D2O)-induced shape changes, movements and F-actin redistribution in human neutrophil granulocytes. AB - Heavy water (D2O) induces characteristic shape changes and a distinct type of movement in human neutrophil granulocytes. In contrast to front-tail polarity as evoked by chemotactic peptides and microtubule-disassembling agents, D2O-based media produce non-polar neutrophils with many small or long surface projections. This phenotype is similar to that elicited by both phorbol myristate acetate and diacylglycerols, but the surface projections are smaller and more densely placed and are often associated with a single large projection. D2O-induced non-polar cells with surface projections perform continuous shape changes without front tail polarity and without the unidirectional movement and cytoplasmic streaming seen in cells with front-tail polarity. Some of the cells show circus movements of a large projection indicating circular polarity. In neutrophils suspended in D2O, F-actin is shifted to the cell periphery, mainly into the surface projections of activated cells. The D2O-induced effects are reversed in H2O-based medium. D2O is dominant over the chemotactic peptide, N-formyl-L-methionyl-L leucyl-L-phenylalanine (fMLP), colchicine and taxol in that the combined action of D2O with any of these agents results in the D2O-induced phenotype. In contrast, cytochalasin B alone and in combination with fMLP induces a considerable decrease of non-polar cells and an increase of spherical cells similar to non-stimulated cells in H2O-based medium. Earlier studies indicated that D2O acts on microtubules. Our results suggest that D2O may act on the microfilament system. Neutrophils suspended in D2O-based medium may represent a useful model to study the relationship between shapes, movements, and particular functions of these cells. PMID- 2907484 TI - Characterization of methamphetamine effects on the striatal-nigral dynorphin system. AB - Multiple high doses of methamphetamine (METH) induced 200-300% increases in the concentration of striatal and nigral dynorphin-like immunoreactivity (DLI). Increases in striatal and nigral DLI levels also were seen within 6 h following a single administration. The changes in the striatal-nigral dynorphin system had subsided 48 h after either acute or multiple treatments with METH. Selective lesioning of the nigral-striatal dopamine pathway blocked the effects; thus, the METH-induced changes appeared to be mediated by dopamine released from the nigral striatal dopamine projection. Administration of the METH analog, 3,4 methylenedioxymethamphetamine, appeared to alter striatal and nigral DLI concentrations in a manner similar to that of METH. PMID- 2907485 TI - Alpha 2-adrenoceptor antagonist activity may account for the effects of buspirone in an anticonflict test in the rat. AB - The anxiolytic effects of buspirone, its metabolite, 1-(2-pyrimidyl)piperazine (1 PP) and several alpha 2-adrenoceptor antagonists have been compared in an anticonflict (shock-induced suppression of drinking) paradigm in rats. Idazoxan, WY 26392 and yohimbine had anticonflict effects comparable to those of buspirone and 1-PP, and enhanced the release of suppressed responding induced by buspirone. The response to buspirone was antagonised by the alpha 2-adrenoceptor agonist clonidine. In tests of clonidine-induced mydriasis, the antagonist potencies of buspirone, 1-PP, idazoxan, WY 26392 and yohimbine corresponded closely to the doses of the compounds active in the anticonflict test. Clonidine-induced hypolocomotion was also antagonised by 1-PP, although this response was potentiated by buspirone. The results suggest that the anticonflict effects of buspirone involve an alpha 2-adrenoceptor mechanism. PMID- 2907486 TI - Absence of receptor reserve at striatal dopamine receptors regulating cholinergic neuronal activity. AB - N-propylnorapomorphine (NPA) dose dependently increased rat striatal ACh levels (ED50 = 18 micrograms/kg). After irreversible dopamine (DA) receptor inactivation with N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), neither the ED50 nor the slope of the dose-response curve for NPA was altered, whereas the maximal response was reduced to 56% of control. Analysis of the results yielded a linear relationship between receptor occupancy and response (i.e. no receptor reserve). In contrast, DA autoreceptors display a large receptor reserve for NPA. The results support the hypothesis that a differential receptor reserve at pre- vs. postsynaptic DA receptors in rat striatum accounts for the autoreceptor selectivity of DA agonists. PMID- 2907487 TI - Spontaneous activity of A9 and A10 dopamine neurons after acute and chronic administration of the selective dopamine D-1 receptor antagonist SCH 23390. AB - The effects of acute and chronic treatment with the selective dopamine (DA) D-1 antagonist SCH 23390 on the population response of midbrain DA cells were determined. One hour pretreatment with SCH 23390 (0.0125, 0.025, 0.05 mg/kg s.c.) caused a dose-related increase in the number of spontaneously firing DA neurons in both the A9 and A10 cell regions. Chronic (28 day) administration of SCH 23390 (0.05 mg/kg s.c.) caused depolarization inactivation of only A10 DA cells. These data suggest that SCH 23390 may have antipsychotic properties with a reduced likelihood of producing extrapyramidal side effects. PMID- 2907488 TI - Effects of the novel benzodiazepine agonist quazepam on suppressed behavior of monkeys. AB - Behavioral effects of the benzodiazepine agonist quazepam were compared with those of lorazepam in squirrel monkeys responding under a fixed-interval schedule of food presentation with a superimposed fixed-ratio schedule of response produced shock. Low and intermediate i.v. doses of quazepam (0.1-1.0 mg/kg) and lorazepam (0.03-0.3 mg/kg) increased rates of suppressed responding, yet the maximal increases in rate were less after quazepam than after lorazepam. Higher doses of both drugs tended to increase responding less or decrease it and, with quazepam, frequent sleep was observed for 2-3 days afterwards. The dose-response curves for quazepam and lorazepam were shifted to the right following i.v. pretreatment with the benzodiazepine antagonists Ro 15-1788 (0.18-3.0 mg/kg) or AHR-11797 (1.0-5.6 mg/kg); in this regard, AHR-11797 was less potent than Ro 15 1788. Although the effects of quazepam on suppressed responding are likely due to actions at benzodiazepine receptors, these effects may be influenced by or reflect a more prominent sleep-promoting action of the drug. PMID- 2907489 TI - [Phe8 psi(CH2-NH)Arg9]bradykinin, a B2 receptor selective agonist which is not broken down by either kininase I or kininase II. PMID- 2907490 TI - Regional vasodilation is a prominent feature of the haemodynamic response to endothelin in anaesthetized, spontaneously hypertensive rats. PMID- 2907491 TI - Inactivation of dopamine D-1 or D-2 receptors differentially inhibits stereotypies induced by dopamine agonists in rats. AB - Ex vivo D-1 or D-2 receptor binding in the striatum was reduced by 65-78% after treatment with EEDQ (N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline) in combination with either the D-2 antagonist, raclopride, or the D-1 antagonist, SCH 23390, respectively. EEDQ induced a 65% reduction in D-1 receptor binding and a 51% decrease in cAMP production in striatal homogenates. Selective D-2 receptor inactivation inhibited the stereotyped behaviour induced by the mixed D-1/D-2 agonist, apomorphine, or by the D-2 agonist, quinpirole, when given alone and in combination with the D-1 agonist, SK&F 38393. Selective inactivation of D-1 receptors did not inhibit the behavioural effects of quinpirole when given alone and in combination with the D-1 agonists, SK&F 81297, SK&F 38393 or SK&F 75670. Likewise, the effect of apomorphine was unchanged. These results indicate that a normal density of D-2 receptors is critical for the expression of the stereotyped behaviour induced by DA agonists. In contrast, there is a large surplus of D-1 receptors to enable the response to a D-2 agonist. This is particularly illustrated by the persistent behavioural effects of the partial D-1 agonist, SK&F 75670, in rats with up to a 78% decrease in D-1 receptor binding. PMID- 2907492 TI - In vitro degradation of opioid peptides by human placental aminopeptidase M. AB - The degradation of opioid peptides by human placental aminopeptidase M was studied by measuring liberated amino acids by high performance liquid chromatography. The purified placental aminopeptidase M actively degraded Met enkephalin (Met-Enk) and Leu-enkephalin (Leu-Enk) completely into constituent 5 amino acids. The activities as a function of tyrosine liberation were observed for Met-Enk followed by Leu-Enk, beta-neoendorphin, dynorphin, and beta endorphin. PMID- 2907493 TI - [Effect of the neuromediator systems of the neostriatum on immunocompetent cells]. AB - The stimulation of the rat neostriatum dopaminergic system (with apomorphine) or blocking of the GABA-ergic (with picrotoxin) and serotoninergic (with parachlorphenylalanin) systems increased the level of immunological indices, whereas the lesion of dopaminergic system (with 6-hydroxydopamine) or the activation of two latter neurotransmitter systems (with GABA and serotonin, resp.) suppressed the immunogenesis. PMID- 2907494 TI - Gastrin, somatostatin, and alimentary tract growth responses to small intestinal resection in the rat. AB - We studied the early time-course of gastrin, somatostatin, and gut growth responses to 70% resection of mid-small intestine. Serum and antral gastrin increased by the 2nd day following resection and remained elevated for the 10-day period of study. Antral somatostatin remained unchanged, suggesting that the increase in gastrin was a selective antral response. Duodenum and ileum showed marked growth stimulation, which was progressive with time, and earlier and greater in duodenum. In contrast, gastric growth was unaffected. Thus, early responses to resection are characterized by specificity of gastrin, somatostatin, and growth effects. PMID- 2907495 TI - [Drug treatment of pain]. PMID- 2907497 TI - Anti-IgM antibodies inhibit IgM expression in lipopolysaccharide-stimulated normal murine B-cells: study of RNA metabolism and translation. AB - Activation of resting mouse B-cells with anti-immunoglobulin M (IgM) antibodies and a mitogen such as bacterial lipopolysaccharide leads to a specific inhibition of IgM expression. [3H]Uridine pulse-chase experiments show that the inhibition of RNA metabolism by anti-IgM antibody treatment occurs in the nucleus at the mu RNA processing level and results in low levels of mature mu-mRNA expression. By applying the RNA synthesis inhibitor 5,6-dichloro-1-beta-D ribofuranosylbenzimidazole, the half lives of various forms of Ig-mRNA are estimated to be 8-12 h. The fact that the residual mu-mRNA left in B-cells after anti-IgM antibody treatment can still be translated into polypeptides indicates that the mu-mRNA in these cells is still functional. PMID- 2907496 TI - Post-transcriptional control in Escherichia coli: translation and degradation of the atp operon mRNA. AB - An attractive subject for investigations of post-transcriptional control is the atp operon, whose nine genes are differentially expressed. The primary mode of control of atp gene expression is exercised at the translational level. It has been clearly demonstrated for almost all of the atp genes that the primary and secondary structures of their respective translational initiation regions direct translational initiation rates that correspond well to the requirements for these subunits in the cell. The relationship between the structure of the translational initiation region, including bases upstream from the Shine-Dalgarno region and downstream from the start codon, and the rates of initiation that it determines, has been investigated in more detail using various polycistronic and monocistronic systems. No evidence could be found for a role of codon usage bias in controlling overall translation rates. The functional half-lives of atpE and of the other six cistrons downstream from it are similar. The chemical stabilities of the first two cistrons of the polycistronic atp mRNA may, however, be lower, and we are investigating the possibility that there may also be control of atp gene expression exercised at the level of mRNA stability. The effects of manipulations of the intercistronic regions of at least the plasmid borne atp operon are consistent with a model of mRNA decay in which rate control is associated with endonucleolytic cleavages within individual cistrons. The experimental data are discussed in relation to the possible ways in which primary and secondary structures of the mRNA might control translational efficiency and stability. PMID- 2907498 TI - The primary structure of human gamma-glutamyl transpeptidase. AB - A cDNA hybridizable to that of rat gamma-glutamyl transpeptidase (GGT) was cloned from a cDNA library of human fetal liver. The insert of the cDNA clone contained 1866 bp consisting of an open reading frame (ORF) of 1709 bp (569 amino acids (aa), N-terminal portion truncated) and a 135-bp 3'-untranslated region followed by a polyadenylated tail. In parallel, amino acid sequences of N-terminal portions of heavy and light chains of a purified human GGT were determined. Two stretches of amino acid sequences identical to the N-terminal sequences of heavy and light chains were found in the ORF. We therefore concluded that the clone is a cDNA for human GGT. From the amino acid sequence deduced from cDNA, the heavy and the light chains of the purified enzyme are estimated to be composed of 351 aa (Mr 38,336) and of 189 aa (Mr 20,000), respectively. The heavy chain is preceded by a signal peptide of at least 29 aa presumed to be cleaved by bromelain treatment. Six putative N-glycosylation sites are present in the heavy subunit region and one in the light subunit region. Primary structure and hydrophobicity profile are closely similar to those of rat GGT. PMID- 2907499 TI - Sequence analysis of the wheat mitochondrial atp6 gene reveals a fused upstream reading frame and markedly divergent N termini among plant ATP6 proteins. AB - The nucleotide sequence of the wheat mitochondrial gene for subunit 6 (atp6) of the F1F0 ATPase complex has been determined. Unlike bacterial, chloroplast or animal/fungal mitochondrial atp6 counterparts, which encode proteins of about 230 270 amino acids, the wheat mitochondrial atp6 homologue comprises the latter part of an open reading frame (ORF) of 386 codons. The ATP6 protein may therefore by synthesized with a long N-terminal presequence. This is supported by the finding that the ORF is preceded by a conserved sequence block closely related to ones preceding several other actively transcribed wheat mitochondrial protein-coding genes. The fused upstream ORF is similar in length, but unrelated in sequence, to those preceding the maize and tobacco mitochondrial atp6 genes. In wheat, the atp6 gene is located on a recombinationally active repeated DNA element, whose length of 1.4 kb corresponds approximately to that of the atp6 mRNA. A comparison of the wheat and maize ATP6 sequences reveals unexpectedly high divergence in the region corresponding to the mature N-terminal domain and may reflect mitochondrial DNA rearrangements during atp6 gene evolution in monocotyledonous plants. PMID- 2907501 TI - Factors influencing dopaminergic therapy of Parkinson's disease. PMID- 2907500 TI - Multiple ligninase-related genes from Phanerochaete chrysosporium. AB - We have investigated four distinct sequences in genomic DNA of Phanerochaete chrysosporium that show strong homology to a lignin peroxidase cDNA sequence [Tien and Tu: Nature 236 (1987) 520-523, and 328 (1987) 742]. The complete nucleotide sequence of one of these genes is presented here. Comparison of the sequenced gene, LIG1, with the published cDNA sequence reveals the presence of eight short intervening sequences. The open reading frame encodes a polypeptide of 372 amino acids (aa), which includes a 28-aa residue hydrophobic leader sequence. The predicted Mr of the mature protein product is 37,000. Partial sequencing of the other three genes reveals substantial nucleotide and amino acid homology. PMID- 2907502 TI - [Pharmacological investigation of bezafibrate, a hypolipidemic agent (2). Mechanism of the hypolipidemic action of bezafibrate in rats]. AB - The mechanism of the hypolipidemic action of bezafibrate was investigated in rats. Bezafibrate decreased the incorporation of 14C-acetic acid into the liver and serum triglyceride and inhibited liver acetyl CoA carboxylate activity. Bezafibrate increased liver beta-oxidation, but it had no effect on lipolysis and triglyceride secretion from the liver. Bezafibrate accelerated the elimination of serum triglyceride in Intralipid injected rats and increased tissue lipoprotein lipase activity. Bezafibrate decreased the incorporation of 14C-acetic acid into liver cholesterol and inhibited liver HMG-CoA reductase activity. Bezafibrate had no effect on cholesterol absorption and excretion. These results suggest that the hypotriglyceridemic actions of bezafibrate are due to inhibition of triglyceride synthesis and acceleration of triglyceride elimination and that the hypocholesterolemic action of bezafibrate is mainly due to inhibition of liver HMG-CoA reductase activity. PMID- 2907503 TI - Nucleotide sequence and expression of the human skeletal alpha-actin gene: evolution of functional regulatory domains. AB - Regulation of the actin multigene family involves the recognition of regulatory sequences that specify the tissue type and developmental program of expression for each actin isotype. In order to investigate the underlying regulatory mechanisms, the human skeletal alpha-actin gene and its 5' regulatory region have been cloned and sequenced. This actin gene has seven exons; there is one large intron in the 5' untranslated region which is characteristic of the actins and many muscle-specific genes. The 5' flanking sequences are sufficient to direct tissue-specific and differentiation-regulated expression when transfected into the heterologous rat L8 myogenic cells, indicating a highly conserved regulatory system. The DNA sequence was compared to that of other actin genes, and several regions of sequence similarity were identified, particularly within regions known to be important for gene expression. Most notable among the conserved sequences are the CC(A/T rich)6GG (CArG box) motifs which have demonstrated interactions with trans-acting transcriptional factors. This same motif has been identified in several other genes and in some also serves as a binding site for transcription regulatory factors. PMID- 2907504 TI - Localization of a human Na+,K+-ATPase alpha subunit gene to chromosome 19q12--- q13.2 and linkage to the myotonic dystrophy locus. AB - The gene coding for a Na+,K+-ATPase alpha subunit (ATP1A3) has been localized to the q12----q13.2 region of human chromosome 19, potentially close to the myotonic dystrophy (DM) gene. In view of previous studies implicating a Na+,K+-ATPase in the pathology of DM, we have examined the possibility that ATP1A3 is a candidate for the DM locus. Although linked, several clear instances of recombination between ATP1A3 and DM rule out the possibility that mutations in ATP1A3 cause the disease. Examination of multiply informative pedigrees indicates the gene order DM-APOC2-ATP1A3. PMID- 2907505 TI - An extended genetic linkage map of markers for human chromosome 10. AB - We have extended, in both directions, our recently published genetic map of markers for human chromosome 10 by the addition of 10 newly defined arbitrary loci. The map now covers 230 cM in males and 329 cM in females. In addition, three new markers, one of them a new RFLP at the IRBP gene locus, have been mapped in the vicinity of the locus responsible for multiple endocrine neoplasia type 2A (MEN2A). A significantly higher frequency of recombination in males than in females was observed near both ends of the new map. PMID- 2907506 TI - RFLPs and linkage relationships of the human laminin B2 gene. AB - RFLPs for laminin B2 (LAMB2) are reported. These RFLPs were used to study the linkage relationships of LAMB2 to four other genes on lq: Duffy (FY), renin (REN), decay accelerating factor (DAF), and complement receptor 2 (CR2). Multipoint linkage analysis placed LAMB2 between FY and the cluster including REN, DAF, and CR2. This provides a useful bridging polymorphic marker on lq and establishes significant linkage of LAMB2 to FY (theta = 3.23, z = 3.85) and REN (theta = 0.17, z = 4.88). PMID- 2907507 TI - Linkage relationships of the human methylmalonyl CoA mutase to the HLA and D6S4 loci on chromosome 6. AB - The human methylmalonyl CoA mutase (MCM) cDNA has been used to localize the MUT locus on the short arm of chromosome 6 proximal to the glyoxalase locus in 6p deletion cell lines. A HindIII polymorphism identified by the MCM cDNA was used to study linkage relationships of MUT to HLA (A-B-DQ-DR) and D6S4 in the reference CEPH families. The maximum lod score for MUT versus HLA was 3.04 at a recombination fraction of 0.28. The maximum lod score for MUT versus D6S4 was 22.93 at a recombination fraction of 0.01. These data suggest that MUT and D6S4 loci are tightly linked and may be used as one locus in a haplotype form for linkage studies on proximal 6p and diagnostic analysis of pedigrees with mut methylmalonic acidemia. PMID- 2907508 TI - Studies on the regulation of enzymes related to fatty acid synthesis in goat mammary gland using explant culture system. PMID- 2907509 TI - The antigen/receptor specificity of antigranulocyte antibodies in patients with SLE. AB - The antigen/receptor specificity of antigranulocyte antibodies (AGAs) detected in the sera of patients with systemic lupus erythematosus (SLE) was investigated by inhibitory immunofluorescence test and Western immunoblotting technique. The interactions of AGAs with antigens of intact normal granulocytes were determined by inhibiting the binding of different myeloid monoclonal antibodies (mAbs). Seven of the studied 12 sera revealed binding to CD15 (X hapten) and/or to CD16 (FcR1o). The specificity investigation of AGAs was completed with Western immunoblotting technique. The binding of AGAs to bands with Mr of about 50-60 kDa and at 30 kDa on unstimulated granulocyte plasma membrane preparation could be demonstrated from 4 out of 6 AGA positive SLE sera. The cause of the disappearance of bands on the phorbol-myristate-acetate (PMA) activated membrane except those of the 50-60 kDa bands is still to be discovered. PMID- 2907510 TI - Effect of histamine and serotonin on phagocytic activity of Entamoeba histolytica. PMID- 2907511 TI - Genetics and epidemiology of sickle cell anemia in India. PMID- 2907512 TI - Records of man-biting mosquitoes of Tezpur (Assam)--a preliminary investigation. PMID- 2907513 TI - Peptide conformations--49(1): synthesis and structure-activity relationships of side chain modified peptides of cyclo(-D-Pro-Phe-Thr-Lys-Trp-Phe.). AB - Cyclic hexapeptide analogues representing the modified retro sequence of the amino acid residues 7-11 of natural somatostatin are known to protect liver cells from phalloidin poisoning. To determine the influence of steric, lipophilic, and charge effects on (a) the conformation of the backbone and the aromatic side chains and (b) the biological response, the side chains of Phe2, Lys4, and Phe6 of cyclo(-D-Pro1-Phe2-Thr3-Lys(Z)4-Trp5-Phe6-), 1a, one of the most active peptides found so far, were modified by various residues. The discussion of conformationally relevant parameters proves that neither backbone conformations nor populations of aromatic side chain rotamers were altered by these substitutions. The potency of these derivatives in a cytoprotection assay varies by at most one order of magnitude (more or less active than the parent peptide 1a). A qualitative evaluation of lipophilic, steric, and charge effects reveals the dominance of lipophilic effects of aromatic residues; the most potent compounds contain aromatic substructures in the side chain of Lys4. PMID- 2907514 TI - Glutamine synthetase from a cyanobacterium, Phormidium lapideum: purification, characterization, and comparison with other cyanobacterial enzymes. AB - Glutamine synthetase has been purified to homogeneity from cell extracts of a non N2-fixing filamentous cyanobacterium, Phormidium lapideum. The subunit molecular weight of the enzyme was determined as about 59,000 by sodium dodecyl sulfate gel electrophoresis. Electron micrographs of the Phormidium enzyme revealed a two layered structure of regular hexagons (12 subunits per molecule), which markedly resembles the three-dimensional polypeptide backbone structure of the Salmonella typhimurium glutamine synthetase established by X-ray crystallography (Almassy, Janson, Hamlin, Xuong, & Eisenberg (1986) Nature 323, 304-309). The N-terminal amino acid sequence of the Phormidium enzyme shows very high similarity with that of the enzyme from an N2-fixing cyanobacterium, Anabaena 7120; 18 residues are common in 23 residues compared. Strong immunocross-reactions between the antibody against the purified Phormidium glutamine synthetase and other cyanobacterial enzymes except the Anacystis enzyme were observed. The apparent Michaelis constants for NH3, L-glutamate, and ATP were determined to be 0.29, 7.4, and 1.7 mM, respectively. Divalent metal ions such as Mg2+ and Mn2+ activated the enzyme in the biosynthetic reaction, whereas various amino acids and glutamate analogs strongly inhibited the enzyme. PMID- 2907515 TI - Simultaneous determination of buspirone, gepirone, ipsapirone and their common metabolite 1-(2-pyrimidinyl)piperazine in rat plasma and brain by high performance liquid chromatography. PMID- 2907517 TI - Direct enantiomeric separation of betaxolol with applications to analysis of bulk drug and biological samples. AB - A direct method is described for the resolution of the enantiomers of betaxolol, a novel cardioselective beta-adrenergic blocking agent, using a tris(3,5 dimethylphenylcarbamate)cellulose chiral column. An excellent resolution of the two antipodes is obtained (Rs greater than 2) with high peak symmetries. The method is simple and ideally suited to the routine control of the enantiomeric excess in the bulk drug and the analysis of the enantiomers of betaxolol in hepatocyte suspensions. With modification of the polar modifier in a hexane-based mobile phase, most commercially available beta-blockers can be baseline resolved. PMID- 2907516 TI - Measurement of the distribution coefficients of several classes of drug using reversed-phase thin-layer chromatography. AB - Using reversed-phase thin-layer chromatography, with octan-1-ol as stationary phase and phosphate buffer (pH 7.4) as mobile phase, the behaviour of different drugs at 37 degrees C was studied. Three classes of drug were examined: beta adrenoceptor antagonists, non-steroidal anti-inflammatory agents and dihydropyridine calcium antagonists. As well as ranking these compounds in terms of their distribution coefficients, an attempt was also made to assign a quantitative value to each. For the beta-adrenoceptor antagonists this was done by using a series of published values obtained using the shake-flask technique: for the non-steroidal anti-inflammatory agents a series of standard compounds was used. No good calibration data were available for the dihydropyridine calcium antagonists, but approximate values were assigned. The results obtained were compared with other published data and the applicability of the method discussed. PMID- 2907518 TI - Determination of a new non-benzodiazepine anxiolytic and its O-demethyl metabolite in plasma by high-performance liquid chromatography using automated column-switching. AB - An highly sensitive and fully automated high-performance liquid chromatographic assay was developed for the determination of a novel non-benzodiazepine anxiolytic (I) [(R)-2-(methoxymethyl)-1-[(7-oxo-8-phenyl-7H-thieno[2,3 a]quinolizin+ ++- 10-yl)carbonyl]pyrrolidine] and its O-demethyl metabolite (II) in plasma, using column-switching for direct injection of plasma samples. After dilution in internal standard solution, the sample was injected onto a pre-column (17 mm x 4.6 mm) dry-packed with pellicular C18 reversed-phase material. Polar plasma components were removed by flushing the pre-column with water-acetonitrile (90:10, v/v). Retained substances, including I and II, were backflushed onto an analytical column, separated by gradient elution and detected by means of fluorescence detection (excitation, 304 nm; emission, 475 nm). After washing the analytical column and re-equilibrating the pre-column, the system was ready for the next injection. The limit of quantification for I and II was 0.25 and 0.5 ng/ml, respectively, using a 350-microliter specimen of plasma. The practicability of the new method was demonstrated by analysis of more than 300 plasma samples from a tolerance study performed with human volunteers. Owing to its high sensitivity, the method can be used to calculate pharmacokinetic parameters of compounds I and II in man after a single oral dose of about 1 mg of I. PMID- 2907519 TI - Serotonergic blockade compared with beta-adrenergic blockade in systemic hypertension: a double-blind comparison of ketanserin with propranolol. AB - The safety and efficacy of ketanserin, a competitive serotonin blocking agent, and propranolol were compared in 33 patients with mild to moderate hypertension (sitting diastolic blood pressure [DBP] 95-115 mm Hg) using a placebo run-in, randomized, double-blind parallel study design. All patients received placebo for 4 weeks, then were randomized to receive increasing doses of either ketanserin (20, 40 mg twice daily) or propranolol (40, 80 mg twice daily) to achieve a goal sitting DBP less than 90 mm Hg. Patients not achieving the goal blood pressure with either drug as monotherapy, received the other drug in combination. At the end of the active monotherapy phase (week 10 of the study), propranolol demonstrated a greater decrease in DBP from baseline, as compared to ketanserin ( 7.9 +/- 10.9 mm Hg with propranolol, P less than 0.05; -1.0 +/- 7.2 mm Hg with ketanserin, P = NS). Four out of 16 patients achieved goal response on propranolol, compared to 3/17 for ketanserin. With combination treatment, 9/18 patients reached the goal response; the addition of propranolol to ketanserin in non-responders resulted in further reduction of sitting DBP of -10.3 +/- 6.3 compared to monotherapy (P less than 0.001), while the addition of ketanserin to non-responders produced no significant response in sitting DBP. Propranolol showed a consistent effect in slowing heart rate. Ketanserin displayed less frequent side effects than propranolol. Propranolol used twice daily appears to be more effective than twice daily ketanserin use in patients with mild to moderate hypertension. PMID- 2907520 TI - Pharmacodynamic comparison of L-bunolol with propranolol, metoprolol, and placebo. AB - Twelve healthy volunteers received single oral doses of propranolol (80 mg), metoprolol (100 mg), L-bunolol (2 mg), and placebo in a four-way crossover study. Blood pressure, ventricular rate, and echocardiographically determined ejection fraction, ejection time, and mean rate of circumferential fiber shortening (mVcf) were measured before dosing and at multiple time points during 10 hours after each dose, with subjects maintained in the supine position. Reductions in systolic and diastolic blood pressure following administration of each of the beta blockers were greater than those observed with placebo, but differences among the four treatments were not significant. Heart rate reductions with the beta blockers differed significantly from placebo (P less than .001), but differences among the three beta blockers were not significant. Differences among the four treatments in mVcf decrement did not attain significance at the 5% level (.05 less than P less than .1), and there were no significant differences in ejection-time prolongation or ejection-fraction reduction. Thus, reduced blood pressure, heart rate slowing, and reduced cardiac contractility may be associated with placebo treatment and may indicate the need for placebo controls in studies of the cardiovascular effects of beta blockers. Despite differing secondary pharmacologic properties, the three beta blockers reduced heart rate to a similar extent. Other effects of the beta blockers on blood pressure and cardiac contractility could not be consistently distinguished from those associated with placebo. PMID- 2907521 TI - Lack of interaction between nizatidine and warfarin during chronic administration. AB - Nizatidine is a new antagonist of H2 receptors. The nizatidine warfarin interaction was investigated in healthy volunteers during chronic warfarin (mean warfarin dose: 5 +/- 0.9 mg/d) and nizatidine (300 mg/d) administration. Nizatidine coadministration did not increase the prothrombin time, kaolin cephalin clotting time, and did not modify the activity of clotting factors II, VII, IX, X. Nizatidine did not influence the steady-state plasma warfarin concentration. PMID- 2907522 TI - Multiple opioid peptides and the modulation of pain: immunohistochemical analysis of dynorphin and enkephalin in the trigeminal nucleus caudalis and spinal cord of the cat. AB - Using immunocytochemistry, we have identified important differences in the distribution of immunoreactive dynorphin and enkephalin cells and terminals in the trigeminal nucleus caudalis and in the spinal dorsal horn of the cat. Dynorphin immunoreactive processes are more closely associated with those regions of cord that process nociceptive information, specifically laminae I and V. Enkephalin neurons and terminals are more widespread. Based on the staining pattern with an antiserum to the octapeptide-metenkephalin-arg-gly-leu, we suggest that the dense enkephalin terminal immunoreactivity in the inner part of the substantia gelatinosa derives from cells in lamina III. There are also significant differences in the anatomical relationship of the two opioid peptides with the organization of parasympathetic autonomic preganglionic neurons. The functional significance of these observations must await physiological analysis; nevertheless, it is almost certain that differences will be found and that these will be important in understanding the mechanisms through which exogenous opiates and a variety of descending control systems exert their effects on spinal cord neurons. PMID- 2907523 TI - Test of radiographic interpretation: lateral projection of the foot. PMID- 2907524 TI - Temporal relationship between onset of Graves' ophthalmopathy and onset of thyroidal Graves' disease. AB - The temporal relationship between the onset of Graves' ophthalmopathy and the onset of thyroidal Graves' disease was evaluated in 125 consecutive patients with Graves' ophthalmopathy. Thyroidal Graves' disease--past or present--was clinically evident in 99 patients (79%): hyperthyroidism in 3 cases. Thyroid disease preceded the eye disease in 37 patients, it occurred simultaneously with the eye disease in 39 patients, and it developed after the eye disease in 23 patients (in 16 cases within one yr after the onset of eye disease). The age at the onset of thyroid disease (38.7 +/- 12.9 yr) was lower than the age at the onset of ophthalmopathy (41.8 +/- 12.5 yr; p less than 0.001). Among the 26 clinically euthyroid patients (21%) laboratory evidence of thyroidal Graves' disease was found in 14 cases (11%): abnormal TRH test, n = 9; normal TRH test but abnormal T3-suppression test, n = 4; normal TRH and T3-suppression tests but positive thyroid stimulating antibodies, n = 1). We conclude that Graves' ophthalmopathy as a rule develops at a time when thyroid autoimmunity also exists. This strongly suggests a common factor in the pathogenesis of thyroidal and ocular expressions of Graves' disease. PMID- 2907525 TI - [Relationship between esophageal candidiasis and histamine H2-receptor antagonists]. PMID- 2907526 TI - Glycolipid stage-specific embryonic antigens (SSEA-1) in kidneys of male and female C57BL/6J and beige adult mice. AB - SSEA-1 glycolipids from the kidneys of normal male and female as well as beige mutant mice were isolated and their structures were examined by component analysis, mass spectrometry, immunoblotting, and permethylation studies. These antigens were shown to be extended globoside derivatives as reported by Sekine et al. (1987. J. Biochem. 101:553-562). Quantitative high performance liquid chromatography analyses revealed that the concentration of SSEA-1 glycolipids were four-to fivefold greater in male than female mice. Essentially no SSEA-1 glycolipids were excreted in the urine of normal male mice and thus are not components of the multilamellar lysosomes normally excreted. Testosterone is known to induce the hypertrophy of proximal tubule cells that involves the formation of multilamellar lysosomes and results in the accumulation and excretion of these bodies and associated lysosomal enzymes and specific glycolipids. The present results indicate that in male mice there is also an increase in subcellular structures that contain SSEA-1 glycolipids. The amount of SSEA-1 glycolipids in male beige mice were greater than in normal mice on a per kidney basis. Thus, the increase is in proportion to the kidney hypertrophy seen in beige mouse kidneys. Beige mutant mice appear to have a primary defect in the excretion of multilamellar lysosomes which produces a secondary hypertrophy with an accompanying increase in SSEA-1 glycolipids. PMID- 2907527 TI - Small comfort: the introduction of minor tranquilizers to the public and the medical profession. PMID- 2907528 TI - An epidemiological and clinical analysis of propylhexedrine abuse in the United States. PMID- 2907529 TI - [Reactions and interactions of drugs]. PMID- 2907530 TI - Multiple compression and plasto-elastic behaviour of paracetamol and microcrystalline cellulose mixtures. AB - Radial tensile strength, friability, ER/PC (elastic recovery/plastic compression) ratio and energy ratio analyses were evaluated for various mixtures of paracetamol and microcrystalline cellulose (Avicel). A good correlation occurred between the energy ratio and the other variables. Linear relationships were found between log tensile strength and percentage energy ratio and also between radial tensile strength and stress relaxation energy. Capping occurred when the percentage energy ratio was greater than 15% and the ER/PC ratio greater than 1.5. To produce tablets with acceptable tensile strength and friability, the percentage energy ratio for Avicel/paracetamol should be greater than 10%. The optimal mixture of the two powders, as far as the tensile strength, friability and absence of capping were concerned, was found to be 50% w/w Avicel, 50% w/w paracetamol. PMID- 2907531 TI - Thermal studies on the interaction of water and microcrystalline cellulose. AB - The interaction between water and microcrystalline cellulose in the absence and presence of lactose has been studied by thermogravimetric analysis, differential thermal analysis and immersional calorimetry. The results indicate that most of the water held within a system used for the preparation of spherical granules by extrusion/spheronization is present as free water which may be readily lost by evaporation. There is approximately 0.856 mol of water per 100 g of microcrystalline cellulose which appears to be absorbed as structured water. Microcrystalline cellulose may therefore be described as a 'molecular sponge'. The enthalpy of fusion of the 'free' water offers a simple method of estimating the effective surface area of the microcrystalline cellulose. PMID- 2907532 TI - A method to study the kinetics of oral mucosal drug absorption from solutions. AB - A method has been developed which allows the kinetics of oral mucosal drug absorption from solutions to be studied in a single 15-20 min test. This is an improvement over the traditional buccal absorption test which requires a separate experiment for each time point, thus taking days for each kinetic profile. It should also allow for disappearance of drug from the mouth and appearance in the plasma to be monitored simultaneously. The drug solution includes 8 micrograms mL 1 phenol red as a marker for salivary secretion. Samples are withdrawn at suitable times with a positive displacement pipettor and analysed for drug and phenol red. Salivary volume time data are described by least squares polynominals. Kinetic parameters are estimated by non-linear least squares regression. The method, which requires that phenol red is not lost during a test, provides an internal test for this. It also requires that phenol red and the drug do not interfere with each other's assay, that saliva does not affect the assays of these materials, and that phenol red does not interfere with the absorption of the drug. PMID- 2907534 TI - Binding of drugs to human skin: influencing factors and the role of tissue lipids. AB - For a series of ten drugs with different physicochemical properties, binding to human skin (epidermis and corium) was determined. Epidermis was obtained by suction blistering, and corium was sliced with a microtome (0.2 mm). Binding experiments were performed in dialysis chambers, containing labelled drug solutions. All drugs investigated were bound to epidermis and corium. With one exception, epidermal drug binding was significantly higher than corial binding. Nevertheless, a good correlation between binding of drugs to both skin fractions could be found. In a range from 10(-7) to 10(-3) mol L-1 binding of drugs to both skin fractions is linear and not saturable. A good correlation was found between binding and lipophilicity of drugs, determined as the partition coefficients between an organic phase (octanol or heptane) and phosphate buffer of pH 7.0. The results show that binding to epidermis and corium is not saturable and depends on lipophilicity of drugs, indicating unspecific binding. Further binding experiments were performed with lipid-depleted tissue. Since drug binding to lipid-depleted samples and control samples differ only to a moderate extent, it is suggested, that tissue lipids play a marginal role on drug binding. Hence, drugs are bound to human skin by other components like proteins. PMID- 2907533 TI - Effects of a perfluorochemical blood substitute on diazepam binding by human albumin. AB - The binding of 0.4 microgram mL-1 diazepam and 0.75 mol diazepam mol-1 of albumin by a perfluorochemical (PFC) emulsion, Fluosol-DA, 20%, by human serum albumin (HSA), and by their mixtures, has been examined at ambient temperature. The concentration of free diazepam was determined by standard centrifugation followed by supernatant ultrafiltration. Non-specific loss of diazepam occurred to the ultrafiltration device. This loss was independent of drug concentration and a correction factor was employed to calculate the true free diazepam concentration. Diazepam was extensively bound by the PFC emulsion. The percent free diazepam increased as the emulsion concentration decreased, while the binding of diazepam appeared to be independent of drug concentration. Diazepam did not partition into the pure PFC liquids, indicating that emulsion-bound diazepam is only associated with the emulsifiers of the droplets. Diazepam was extensively bound by HSA and the percent free diazepam increased as drug concentration increased or as HSA concentration decreased. The PFC emulsion significantly displaced HSA bound diazepam in all mixtures examined. Studies with the individual and combined components of the emulsion indicated that this displacement is largely attributed to the oleic acid component and, to a much smaller degree, the Pluronic F-68 component of the emulsion. PMID- 2907535 TI - Hydroxylation of debrisoquine using perfused liver isolated from Sprague Dawley and DA rats: comparison with in-vivo results. AB - The hydroxylation of debrisoquine was investigated in Sprague-Dawley (SD) and Dark-Agouti (DA) rats. Female and male rats were phenotyped in-vivo with debrisoquine six times during their growth. The ratios debrisoquine/4 hydroxydebrisoquine of the female DA rats increased until the 15th week and then decreased; but the values of the metabolic ratios never exceeded 2. Female DA rats cannot be considered as genetically deficient for hydroxylation of debrisoquine in regard to the metabolic ratio, but the percentage of debrisoquine excretion is up to ten fold higher than that in the other strains. Therefore SD and DA rat livers were perfused for 2 h when the clearance of debrisoquine was significantly lower in the female DA group than in the other groups. 4 Hydroxydebrisoquine in the perfusate increased with time, but the amount after 120 min was 12 fold lower in the female DA rat group than in the female SD rat group. The results of the male DA group fell between. This study confirms that female DA rats present a lower debrisoquine 4-hydroxylating capacity than other rats but shows that urinary metabolic ratio is not sufficient to assess the deficiency of debrisoquine hydroxylation. PMID- 2907536 TI - Effect of chlorpromazine on the permeability of beta-lactam antibiotics across rat intestinal brush border membrane vesicles. AB - The effect of chlorpromazine on the membrane permeability of beta-lactam antibiotics (benzylpenicillin, ampicillin, cephradine and cephalexin) and actively transported substances (glycylglycine and D-glucose) has been studied using rat intestinal brush border membrane vesicles. Except for cephalexin, the initial uptakes at 25 degrees C of these antibiotics were significantly enhanced in the presence of chlorpromazine. In contrast, the transport of glycylglycine and D-glucose was significantly inhibited. These results suggest that the two groups, drugs and actively transported substances, have a different permeation process. The effect of chlorpromazine concentration on membrane lipid fluidity, as assessed by the fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1-anilino-8-naphthalene sulphonate (ANS), was also examined. The fluorescence polarization of ANS decreased with increasing concentration of chlorpromazine, while that of DPH increased suggesting an increase of membrane surface fluidity might affect the permeation of beta-lactam antibiotics and actively transported substances in a different manner. PMID- 2907537 TI - Studies in the guinea-pig with ICI 185,282: a thromboxane A2 receptor antagonist. AB - The effects of ICI 185,282 (5(Z)-7-([ 2,4,5-cis]-4-O-hydroxyphenyl-2 trifluoromethyl-1, 3-dioxan-5-yl)heptenoic acid) have been studied on guinea-pig platelets and pulmonary smooth muscle in-vitro and in-vivo. When tested on guinea pig lung parenchyma in-vitro. ICI 185,282 (1 x 10(-7) M) produced a significant shift in U-46619 response curves (concentration ratio of 13:3); the antagonist (1 x 10(-5) M) did not modify histamine responses. When tested on guinea-pig trachea in-vitro ICI 185,282 (1 x 10(-7) M) caused significant inhibition of U-46619 and PGD2 responses (concentration ratios of 8.3 and 14.1, respectively); the antagonist (1 x 10(-5) M proved less effective against contractions of PGF2 alpha, LTD4 and histamine (concentration ratios of 7.0, 1.5 and 1.6). When added to guinea-pig platelet rich plasma in-vitro, ICI 185,282 (x 10(-6), 1 x 10(-5) M) caused concentration-dependent parallel shifts to the right of U-46619 aggregation curves, yielding concentration ratios of 13.6 and 141.9, respectively. In-vitro, addition of ICI 185,282 (x 10(-5) M) to indomethacin treated pulmonary smooth muscle did not modify resting tone, neither did it induce aggregation or swelling in platelet-rich plasma preparations. When administered orally to guinea-pigs ICI 185,282 (0.1, 0.5 mg kg-1) caused a significant inhibition of U-46619-induced platelet aggregation ex-vivo which persisted greater than or equal to 8 h. In-vivo, a single oral dose of ICI 185,282 (1 mg kg-1) inhibited bronchospasm induced by U-46619, PGD2, PGF2 alpha, arachidonic acid, LTD4 and PAF; responses to histamine were unaffected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2907538 TI - Vasoactive intestinal polypeptide as possible mediator of relaxation in the rat gastric fundus. AB - Relaxations were induced in longitudinal muscle strips of the rat gastric fundus by stimulation of non-adrenergic non-cholinergic (NANC) neurons and by administration of vasoactive intestinal polypeptide (VIP) or isoprenaline. The effect of antiserum against vasoactive intestinal polypeptide (VIP antiserum) and of control serum on these relaxations was investigated. Incubation with VIP antiserum (dilution 1/50) for 1 h almost completely prevented the relaxation by VIP. It partially prevented the relaxation evoked by electrical stimulation while the relaxation induced by isoprenaline was not influenced. Control serum decreased the VIP- and stimulation-induced relaxations much less than did VIP antiserum. In addition, the effect of the putative VIP antagonist (4Cl-D-Phe6, Leu17) VIP was studied on the relaxations induced by NANC neuron stimulation and by VIP. The VIP antagonist (3 x 10(-5) M, incubation time 10 min) had a relaxatory effect itself but had no influence on either VIP- or stimulation induced relaxations. The results with VIP antiserum confirm the involvement of VIP in the inhibitory NANC neurotransmission of the rat gastric fundus. PMID- 2907539 TI - External control of drug release: controlled release of insulin from a hydrophilic polymer implant by ultrasound irradiation in diabetic rats. AB - The development of a polymeric system capable of delivering insulin in-vivo at increased rates on demand by an external ultrasound irradiation is reported. Implants composed of EVA1 copolymer and insulin were placed subcutaneously in diabetic rats. When the diabetic rats receiving implants containing insulin were exposed to an ultrasound irradiation, a sharp drop in the blood glucose levels was observed after the irradiation, indicating a rapid rate of release of insulin in the implanted site. PMID- 2907540 TI - Evidence that the kappa agonist U50488H has non-opioid actions. AB - The antagonism of the antinociceptive effects of various kappa-opioid agonists has been studied in the mouse abdominal constriction test. Naloxone produced a much smaller degree of antagonism of U50488H than it did of two other kappa agonists, U69593 and tifluadom. The kappa-selective antagonist, norbinaltorphimine, also failed to shift the dose-response curve to U50488H in this test, despite producing considerable antagonism of the U50488H effect in the rotarod test and of U69593 in both experimental situations. These results are suggestive of a non-opioid component to the action of U50488H in the abdominal constriction test. At high concentrations, U50488H, but not U69593, also showed non-opioid effects in reducing contractile activity in the field-stimulated isolated guinea-pig ileum, as demonstrated by the profile of antagonism seen with beta-chlornaltrexamine and naloxone. These results suggest that U69593, rather than U50488H, may be the kappa-agonist of choice to use, particularly in in-vivo experiments. PMID- 2907541 TI - Cardiovascular effects of intracerebro-ventricular bradykinin and melittin in the rat. AB - The cardiovascular effects of intracerebroventricular (i.c.v.) bradykinin and melittin were investigated in the anaesthetized rat. Bradykinin, 30 micrograms, increased mean arterial pressure by 15 mmHg and this was the result of an increase in peripheral resistance; heart rate and cardiac output were unchanged. Tissue blood flow was lower in the skin and spleen in the animals given bradykinin than the controls. Significant increases in tissue vascular resistance occurred in the skin and several organs of the splanchnic region, the spleen, stomach, large intestine and the pancreas/mesentery. Melittin infusion gave a biphasic response in systemic blood pressure in which a depressor response was followed by a pressor phase; the pressor stage was accompanied by an increase in heart rate. Since melittin is a stimulant of membrane bound kallikrein, the results lend limited support to the hypothesis that there is a kallikrein-kinin system endogenous to the central nervous system which is involved in cardiovascular regulation. PMID- 2907542 TI - Inhibition of histamine N-methyltransferase activity in guinea-pig pulmonary alveolar macrophages by nicotine. AB - Both S-(-)- and R-(+)-nicotine enantiomers are inhibitors of histamine N tau methylation activity in guinea-pig pulmonary alveolar macrophage cultures, exhibiting IC50 values of 7 and 8 microM, respectively. S-(-)-Nicotine is not biotransformed under the conditions of the experiment, however, R-(+)-nicotine undergoes significant N-methylation to produce N-methylnicotinium ion. S-(-) Nicotine appears to inhibit the N-methylation of its optical antipode by the alveolar nicotine N-methyltransferase. The results indicate that a contributing factor in the toxicology of cigarette smoke inhalation may be due to the inhibition of pulmonary metabolism of histamine by nicotine. PMID- 2907543 TI - A rapid and sensitive high-performance liquid chromatographic method for the determination of diclofenac sodium in serum and its use in pharmacokinetic studies. AB - A rapid, and sensitive high-performance liquid chromatographic method has been developed for the determination of diclofenac sodium in serum using flufenamic acid as the internal standard. Serum protein was precipitated with acetonitrile. The drugs were eluted from a 5 microns C-8 reversed-phase column at ambient temperature with a mobile phase consisting of acetonitrile-water (50:50% v/v) adjusted to pH 3.3 with glacial acetic acid, at a flow rate of 2 mL min-1 with UV detection at 280 nm. Each analysis required no longer than 10 min. Quantitation was achieved by the measurement of the peak-height ratio and the relative and absolute recoveries varied from 90 to 98%. Detection limits for diclofenac sodium in serum is 25 ng mL-1. Intraday coefficients of variation (CV) ranged from 2.47 to 4.61% and interday CVs from 3.52 to 7% at three different concentrations. Preliminary stability tests showed that diclofenac sodium is stable for at least 2 weeks in serum after freezing. The method is applied for the determination of the pharmacokinetic parameters of diclofenac after administration of two formulations (enteric-coated tablet and slow-release tablet), to a healthy male volunteer. PMID- 2907544 TI - Digitonin-solubilized histamine H1-receptors bind to polyethylenimine-treated glass-fibre filters. AB - The binding of [3H]mepyramine to histamine H1-receptors solublized from guinea pig cerebellum by 1% digitonin could be assayed by adsorption of the receptor bound [3H]ligand to glass-fibre filters pretreated with 0.3% polyethylenimine (PEI). Non-specific binding was higher than in parallel experiments in which the bound and free [3H]ligand was separated by gel-filtration on Sephadex G-25 columns, but the parameters characterizing the inhibition curves were otherwise similar. The PEI-treated filter method could also be used to assay [3H]-(+)-N methyl-4-methyl-diphenhydramine ([3H]QMDP) binding to solubilized H1-receptors, but the level of non-specific binding was higher and was only satisfactorily defined by icotidine or temelastine. A particular utility of the PEI-treated filter assay will be in measurements of the kinetics of H1-receptor-ligand interactions. PMID- 2907545 TI - Amelioration of glycerol-induced acute renal failure in the rat with 8 phenyltheophylline: timing of intervention. AB - The importance of timing and duration of 8-phenyltheophylline (8-PT) administration in determining its beneficial action in glycerol-induced acute renal failure (ARF) was investigated by examining the effects of a single dose of 8-PT given immediately following (0 h) glycerol injection and at 1 and 3 h after glycerol injection. 8-PT when given at 0 h significantly lowered plasma urea and creatinine concentrations and significantly increased inulin clearance when compared both to untreated animals and those that received the vehicle for the drug. By contrast, 8-PT when administered at 1 h afforded no protective effect on renal function and, when injected at 3 h, the only significant effect was lowered plasma creatinine levels when compared to untreated rats; at this latter time it did not lower plasma urea levels or improve inulin clearance. None of the 8-PT injections attenuated the increase in kidney weight associated with ARF or reduced the kidney damage as assessed by histological examination. The results show that a single administration of 8-PT made immediately following glycerol injection can ameliorate the biochemical and functional indices of impaired renal function, but does not produce an improvement in kidney morphology. PMID- 2907546 TI - Differences in the characteristics of opioid receptor binding in the rat and marmoset. AB - The density of mu and delta opioid binding sites in homogenates of rat and marmoset brain was determined using radiolabelled peptides with high receptor selectivity. In addition the affinity of mu and delta receptor binding of five drugs of the fentanyl series was measured. The ratio of mu: delta sites was similar within each species but the total receptor binding capacity in the rat was double that of the marmoset. The binding affinities for the delta site were dissimilar between the species and supports the hypothesis that the structure of this receptor shows phylogenetic differences. In contrast, mu site binding affinity was identical in rat and marmoset. PMID- 2907548 TI - Prostaglandin synthetase inhibitors in feverfew. AB - The IC50 values for the in-vitro inhibition of the prostaglandin synthetase (bovine seminal vesicle mitochondrial fraction) mediated PGE2 production from arachidonic acid by parthenolide, michefuscalide and chrysanthenyl acetate were 11.0 +/- 0.44, 12.1 +/- 0.51 and 14.2 +/- 0.58 microM (mean +/- 95% confidence limits), respectively. PMID- 2907547 TI - Increased vasodilator response to acetylcholine of renal blood vessels from diabetic rats. AB - The vasodilator effect of acetylcholine (ACh) and nitroprusside and the vasoconstrictor effect of noradrenaline was assessed in the perfused kidney of streptozocin diabetic rats. Compared with control animals injected with acidified saline, the renal vasoconstrictor effect of noradrenaline was increased in diabetic rats both in terms of the dose required to produce 50% of the maximal effect (EC50) and in the maximal response achieved. The renal vasodilator effect of ACh (but not nitroprusside) was similarly enhanced in diabetic animals. The effect of ACh (but not nitroprusside) in the perfused kidney of both control and diabetic rats was reduced or abolished by mepacrine (10 microM), metyrapone (10 microM) or methylene blue (100 microM) suggesting that ACh exhibits vasodilator activity in the rat kidney by virtue of releasing endothelium derived relaxing factor (EDRF). These results are in contrast to previous published reports demonstrating reduced biosynthesis of EDRF in the aorta of diabetic rats. The mechanism which underlies the increased renal vascular response to ACh is not known. However, increased endothelial cell turnover or cholinoceptor number, elevated activity of enzyme(s) which synthesis EDRF or hyperresponsiveness of vascular smooth muscle to released EDRF should all be considered. PMID- 2907549 TI - The local modulation of vascular permeability by endothelial cell derived products. AB - Endothelin has been shown to suppress increased vascular permeability in the rat at doses of 0.01 pmol. The agonists used were nitric oxide and nitroprusside, which have the same activity as endothelial-derived relaxing factor. Histamine, 5 hydroxytryptamine, platelet activating factor and carrageenan were the other agonists used. It is proposed that endothelin and EDRF act as local hormones produced by endothelial cells to control local vascular permeability. PMID- 2907550 TI - Non-dopaminergic actions of quinpirole hydrochloride (LY 171555), a selective D2 agonist, in the guinea-pig isolated ileum. PMID- 2907551 TI - The interaction of dopexamine with various drugs and excipients in parenteral solutions. AB - The interaction of dopexamine hydrochloride with various excipients and other drugs in parenteral solutions has been investigated by microcalorimetry. The interaction with heparin sodium, in particular, is significant. The interaction is strongest in parenterals containing glucose and is eliminated in normal saline. Divalent cations are more effective than monovalent ones in eliminating the reaction, which is apparently ionic in nature. PMID- 2907553 TI - Biotransformation of primary nicotine metabolites: metabolism of R-(+)-[3H-N' CH3; 14C-N-CH3] N-methylnicotinium acetate--the use of double isotope studies to determine the in-vivo stability of the N-methyl groups of N-methylnicotinium ion. AB - The in-vivo metabolism of R-(+)-[3H-N'-CH3; 14C-N-CH3]-N-methylnicotinium acetate (NMN) was studied in the guinea-pig to determine the in-vivo stability of the N methyl and N'-methyl groups of this primary nicotine metabolite. The results showed that N-demethylation does not occur. However, losses of 34 and 36%, respectively, of the 3H label in the N'-CH3 group of urinary NMN and the secondary metabolite, N-methyl-N'-oxonicotinium ion (NMNO), were observed. These results suggest that biotransformation of NMN may involve either an initial N' demethylation step to N-methylnornicotinium ion (NMNor) followed by N' methylation back to NMN, or the formation of an N'-methylene iminium species, which may be reductively converted back to NMN. PMID- 2907552 TI - Preparation of biodegradable poly(+/-)lactide microparticles using a spray-drying technique. AB - Drug containing biodegradable poly(+/-)lactide microparticles were prepared by using a spray-drying technique. Formulations containing model drugs in either a dissolved (progesterone) or dispersed state (theophylline) were spray-dried. The spray-drying method was less dependent on the solubility characteristics of the drug when compared with traditional microencapsulation techniques such as phase separation or solvent evaporation techniques. Differential scanning calorimetry and scanning electron microscopy were used to characterize the microparticles. The drug release profiles were characterized by a rapid release phase (burst effect) followed by a slow release phase, the extent of each phase being dependent on the drug loading. PMID- 2907554 TI - Coprecipitation of enzymes with water soluble starch--an alternative to freeze drying. AB - Krill proteases were prepared in solid form from a partially purified extract by coprecipitation of the enzymes with water-soluble starch in an organic solvent at 22 degrees C. The precipitation did not affect the activity of the enzymes. The recovery of proteolytic activity was 100%. The thermostability of the krill proteases increased when incorporated in the starch precipitate. No reduction in enzymatic activity could be seen after storage at +50 degrees C for 99 days. After milling the coprecipitate could be dispensed. The enzyme preparation consisted of irregular needle-shaped particles. This simple precipitation technique offers an alternative to freeze-drying or spray-drying. PMID- 2907555 TI - Binding of amitriptyline to alpha 1-acid glycoprotein and its variants. AB - Binding studies have been performed between amitriptyline and i) native alpha 1 acid glycoprotein (AAG); ii) its desialylated form; iii) its two variants, S-AAG and F-AAG; and iv) a mixture of S-AAG and F-AAG. Scatchard analysis revealed the presence of two classes of binding sites on AAG. For native AAG, the first class (of high affinity) has an association constant (Ka1) of 1.5 x 10(6) L mol-1 and a number of binding sites per mole of protein (n1) of 0.25, while the second class (of low affinity) has a Ka2 of 3.2 x 10(4) L mol-1 and a n2 of 0.94. Similar data were found for desialylated AAG. S-AAG and F-AAG do not differ in their association constants measured with amitriptyline, but in their number of binding sites per mole of protein (n): S-AAG: n1 = 0.56, n2 = 0.52; F-AAG: n1 = 0.17, n2 = 0.71. These results confirm those of a previous study, in which a higher affinity of S-AAG towards various basic drugs in comparison with F-AAG has been found. PMID- 2907556 TI - The effect of drug-specific active immunization on digoxin and benzylpenicillin disposition in the bile duct-cannulated rat. AB - Rats were immunized with a digoxin-human serum albumin conjugate i.m. This resulted in a several hundred-fold increase in plasma radioactivity and a 90% reduction in biliary drug elimination when [3H]digoxin (10 micrograms kg-1, i.v.) was subsequently injected into anaesthetized bile duct-cannulated rats. It was calculated that about 90% of the drug dose remained antibody-bound within the plasma compartment, with essentially no drug distributing into organs such as the heart and liver. Digoxin-specific antibody levels, determined by equilibrium dialysis, were high in the plasma but at least an order of magnitude lower in the bile. Immunization via Peyer's patches did not increase antibody levels in the bile. Immunization (i.m.) with a benzylpenicillin-human serum albumin conjugate gave specific antibody plasma titres with values less than 10% of those obtained after immunization with a digoxin-protein conjugate. However, although subsequent injection of the hapten (40 micrograms kg-1, [14C]benzylpenicillin, i.v.) was associated with much lower increases and decreases in plasma and biliary radioactivity, respectively, they were still statistically significant. It appears that endogenously-formed drug-specific antibodies, when present in the blood, will inhibit drug distribution and elimination. It is unlikely that their secretion in the bile plays a significant role in mediating biliary drug hapten elimination. PMID- 2907557 TI - Binding of organic cations to brush border membrane from rat small intestine. AB - The binding of six organic cations (chlorpromazine, promethazine, imipramine, diphenhydramine, methochlorpromazine and propantheline) to the brush border membrane isolated from rat small intestine has been investigated. The cations were bound to the membrane to varying extents, the order of binding being chlorpromazine greater than promethazine greater than methochlorpromazine greater than imipramine greater than propantheline greater than diphenhydramine. There was no relation between binding and the chloroform-water partition coefficient. Chlorpromazine binding was significantly decreased in the presence of imipramine, methochlorpromazine and propantheline. Anionic compounds (indomethacin and xanthene-9-carboxylic acid) did not affect chlorpromazine binding. High and low affinity binding of the cations to the intestinal brush border membrane was demonstrated with Scatchard plots and Hill plots. Imipramine and methochlorpromazine inhibited chlorpromazine binding at both binding sites. From the results, it was suggested that the organic cations tested were specifically bound to common binding sites on the brush border membrane. PMID- 2907558 TI - Some pharmacological properties of the circular smooth muscle layer of the rat vas deferens. AB - Vas deferens preparations were perfused in-vitro through the lumen and externally with a modified Tyrode solution alone or containing drugs. Contractions of the circular (internal) smooth muscle layer were recorded as changes in the pressure of internal perfusion. Contractions of the longitudinal (external) layer were simultaneously recorded through a tension transducer. When the organ was perfused through the lumen, the circular layer contracted after addition of methacholine (pD2 = 4.13), and noradrenaline (pD2 = 5.00), and relaxed after addition of isoprenaline (pD2 = 5.22). These effects were also observed when the drugs were perfused externally, although with lower values of pD2 for noradrenaline and methacholine. The circular fibres were less sensitive when compared with the longitudinal fibres perfused externally with the above agonists. Methacholine induced contractions of the circular layer were competitively antagonized by atropine (pA2 = 8.53), indicating the presence of muscarinic receptors. The effects induced by noradrenaline and isoprenaline were antagonized by indoramin (pA2 = 7.78), and timolol (pA2 = 8.68), respectively, indicating the presence of alpha- and beta-adrenoceptors. The effect of noradrenaline was potentiated by cocaine and denervation, indicating the presence of neuronal uptake, and by corticosterone, indicating the presence of extraneuronal uptake in the circular layer. PMID- 2907559 TI - Selectivity of neutrophil 5-lipoxygenase and cyclo-oxygenase inhibition by an anti-inflammatory flavonoid glycoside and related aglycone flavonoids. AB - A newly described plant-derived flavonoid, hypolaetin-8-glucoside, which has anti inflammatory and gastroprotective actions in-vivo, and its corresponding aglycone, hypolaetin, have been compared with 14 other flavonoids for inhibition of eicosanoid generation via the 5-lipoxygenase and cyclo-oxygenase pathways in elicited rat peritoneal leukocytes stimulated with calcium ionophore. Comparable results for the inhibitory profiles of the compounds were obtained using either radioimmunoassay of released eicosanoids or radio-TLC of metabolites formed from labelled arachidonate, but there were differences in absolute potency of the inhibitors. Hypolaetin-8-glucoside was a weak but selective inhibitor of 5 lipoxygenase (IC50 56 microM vs 5-lipoxygenase; greater than 1000 microM vs cyclo oxygenase), whereas the aglycone hypolaetin was a more potent and selective 5 lipoxygenase inhibitor (IC50 4.5 microM vs 70 microM). Results with three other glycoside/aglycone pairs confirmed that addition of sugar residues greatly reduces inhibitory potency whilst retaining selectivity against 5-lipoxygenase. Analysis of 12 aglycone flavonoids showed that inhibitory potency and selectivity against 5-lipoxygenase is conferred by the presence of 3'4'-vicinal diol (catechol) in ring B as part of a 3,4-dihydroxycinnamoyl structure as proposed by others and by incorporation of additional hydroxyl substituents. In contrast, "cross-over" of inhibitory selectivity is observed in compounds containing few hydroxyl substituents (with none in ring B) which are selective against cyclo oxygenase. These results are discussed in relation to possible mechanisms of hypolaetin-8-glucoside's protective actions and the concept that these inhibitory effects of flavonoids cannot be ascribed to a unitary free radical scavenging action. PMID- 2907560 TI - The effect of acute dyflos (DFP) treatment on [3H]nicotine binding to mouse brain homogenate. AB - One possible adaptive mechanism that might arise due to inhibition of cholinesterase in the brain is a down regulation of central cholinergic receptors. Therefore studies were performed to determine the effect of acute dyflos exposure on [3H]nicotine binding. Specific [3H] nicotine binding was demonstrated to be saturable, reversible, stereospecific, and inhibited by a number of nicotinic compounds. Scatchard analysis of specific [3H] nicotine binding produced a curvilinear plot that was resolved into high- and low-affinity sites with Kd values of 6.1 +/- 2.5 and 114 +/- 13 nM, and Bmax values of 11.8 +/ 3.5 and 182 +/- 24 fmol (mg protein)-1, respectively. The nicotinic binding sites in brain homogenate from dyflos-treated mice that were killed 20 min or 10 h after exposure did not exhibit significant alterations in binding parameters from control mouse brain homogenate. However, brain homogenate from treated mice that were killed 24 h after exposure resulted in statistically significant differences in the low-affinity K(D) and Bmax values from controls. Since no alterations were found in the high-affinity binding parameters and dyflos had only a minimal effect on the low-affinity site at 24 h, it was concluded that nicotinic receptor down regulation does not appear to be the mechanism through which the mouse functionally adapts to cholinesterase inhibition caused by acute dyflos treatment. PMID- 2907561 TI - Application of difference spectroscopy to the determination of some pharmaceutically important nitro compounds. AB - A simple and selective spectrophotometric method for the determination of some pharmaceutically important nitro compounds has been developed. The suggested method depends upon the spectral changes induced by reduction using either Zn/HCl or Zn/NH4Cl. The different experimental parameters were studied and incorporated into the procedure. The mean percentage recovery ranged from 99 to 101. The proposed method was applied to the determination of the studied compounds in dosage forms, and the results obtained were compared favourably with those given with the compendial ones. PMID- 2907562 TI - Uterine inhibitory effect of reticuline. AB - Reticuline, the most abundant benzylisoquinoleic alkaloid of Laurobasidium lauri, exerts a uterine inhibitory effect mainly related to a decrease in the concentration of cytosolic calcium available for contraction. PMID- 2907563 TI - Selective beta 2-adrenoceptor antagonists: derivatives of ICI 118,551 and a binary aryloxypropanolamine. AB - Recent studies indicate that selective beta 2-adrenoceptor antagonists may be of use in the treatment of glaucoma. ICI 118,551, its desmethyl-, didesmethyl-, and ethyl- analogues, and a putative highly beta 2-selective binary aryloxypropanolamine (4d) have been evaluated for their ability to inhibit beta adrenergic-stimulated adenylate cyclase activity in rabbit ciliary process and heart. Potency ratios (Ki heart/Ki ciliary process) were 440 for ICI 118,551; 9.3 for the desmethyl analogue; 8.2 for the didesmethyl analogue; 720 for the ethyl analogue; and 11 for the binary aryloxypropanolamine. The values for the ethyl derivative of ICI 118,551 indicate that it is the most oculoselective beta adrenoceptor antagonist yet reported. PMID- 2907564 TI - Effects of indomethacin and diclofenac on some functions of polymorphonuclear neutrophils. AB - The effects in-vitro of two non-steroidal anti-inflammatory drugs, diclofenac and indomethacin, have been studied on human polymorphonuclear functions. Adhesivity and chemotaxis were decreased by the two drugs, but in a manner that varied with the attractant used. As shown by the nitro blue tetrazolium slide test, all cells remained active but the production of oxygen metabolites by opsonized zymosan was decreased in the presence of diclofenac. PMID- 2907565 TI - Equilibrium binding of spermine and histamine to salmon sperm DNA and poly(dGdC). AB - Studies using the solute-enhanced phase partition technique demonstrate that the endogenous amines histamine and spermine bind to both salmon sperm DNA and poly(dGdC) in a markedly cooperative fashion. Both compounds exhibited DNA sequence-dependence effects in their mode of binding. The linear aliphatic spermine molecule binds more strongly than histamine to both DNA types. PMID- 2907566 TI - Relaxant and beta 2-adrenoceptor blocking activities of labetalol, dilevalol, amosulalol and KF-4317 on the rat isolated aorta. AB - The KCl-contracted rat aorta is relaxed by labetalol, dilevalol, amosulalol and KF-4317. These relaxations are not reversed by ICI 118,551 at 10(-6) M and, therefore, are not due to beta-adrenoceptor agonism. At 10(-7) M, labetalol, dilevalol, amosulalol and KF-4317 were beta 2-adrenoceptor antagonists as they inhibited the relaxant responses of rat aorta to procaterol. PMID- 2907567 TI - The influence of components on the rectal absorption of cefazolin in rats. AB - A study has been made to identify the component(s) responsible for the absorption promoting effect of MGK medium chain glyceride preparation commercially available as a mixture of glyceryl-1-monooctanoate, glyceryl-1,3-dioctanoate, glyceryl-1,2 dioctanoate, glyceryl trioctanoate, octanoic acid and glycerol. The action of the individual constituents has been evaluated on the rectal absorption of cefazolin in conscious rats. The results indicate that the action of MGK can be completely explained by the effect of glyceryl-1-monooctanoate, which both enhanced the extent and rate of cefazolin uptake. PMID- 2907568 TI - 4-Methylpyrazole alters phenobarbitone hypnotic concentrations in rats. AB - The liver alcohol dehydrogenase inhibitor, 4-methylpyrazole, has been tested for its ability to change the hypnotic concentrations of phenobarbitone (phenobarbital) in rats. Following a single dose of 1 mmol kg-1 i.v., administered 60 min before phenobarbitone, 4-methylpyrazole shortened the onset time and reduced the dose of phenobarbitone required to produce loss of righting reflex. Consistent with this, phenobarbitone concentrations in serum (both total and free), brain and in cerebrospinal fluid at onset of hypnosis were about half in 4-methylpyrazole compared with saline-treated rats. These results suggest that acute 4-methylpyrazole pretreatment increases the central nervous system sensitivity to phenobarbitone and presumably other barbiturates; an effect apparently distinct from its inhibition of liver alcohol dehydrogenase. PMID- 2907569 TI - The in-vitro percutaneous absorption of glycerol trioleate through hairless mouse skin. AB - The chemical composition of the aqueous receptor fluid in one-chambered diffusion cells used for in-vitro percutaneous absorption studies has been shown to significantly affect the apparent extent of absorption of the triglyceride, glycerol trioleate. Using murine skin samples it was found that the addition of albumin to the receptor fluid resulted in an increase in the apparent extent of absorption, while the presence of the bacteriostatic agent thiomersal resulted in a decrease. The viability of the skin samples had no effect on absorption. It was determined that the chemical species in the receptor fluid was the free fatty acid. Albumin presumably bound the fatty acid, thereby creating a sink which enabled the fatty acid to partition from the skin into the receptor fluid. PMID- 2907570 TI - Action of a chronic arecoline administration on mouse motility and on acetylcholine concentrations in the CNS. AB - The modifications of mouse motility and of the levels of acetylcholine (ACh) in two sections of the CNS caused by a chronic administration of 4.5; 9.5; 28.5 and 60 mg kg-1 day-1 of arecoline for 20 days have been studied. At low doses (4.5 and 9.5 mg kg-1 day-1), arecoline caused no modification of the ACh levels and of the motility. The higher doses (28.5 and 60 mg kg-1 day-1) caused a reduction of the mouse motility and an increase of the ACh levels in the subcortical structures of the CNS of the mouse. PMID- 2907571 TI - Ocular distribution of aspirin and salicylate following systematic administration of aspirin to rabbits. AB - The distribution of aspirin and salicylate 30 min after the intravenous administration of different doses of aspirin has been investigated in the rabbit eye. HPLC enabled a rapid and sensitive determination of both substances. A considerable dose-dependent penetration into all ocular tissues was observed with both aspirin and salicylate. Aspirin concentrations were higher than in plasma in all ocular tissues with the exception of the lens. These results show that an unhydrolysed drug may have a direct local effect by acetylating lens protein or other ocular constituents. PMID- 2907572 TI - A consideration of the range and strength of interparticle forces in coated lactose powder. AB - A study has been made of the range and strength of interparticle forces in lactose powder coated with increasing concentrations of paraffins at different temperatures. Marked changes occurred in these forces as the paraffin content was altered and the temperature increased from -10 degrees to +50 degrees C. The strength and range of interparticle forces depended on the mechanical properties of the coating materials and the surface free energy of the coated powders. PMID- 2907573 TI - Effects of phosphatidylcholine on the topical bioavailability of corticosteroids assessed by the human skin blanching assay. AB - A non-occluded multiple application skin blanching assay has been used to determine the effect of applied phosphatidylcholine (PC) on the bioavailability of corticosteroids. One forearm of each of ten volunteers was treated twice daily for one week with PC presented as a liposomal suspension in Sorensen's (pH 5.0) phosphate buffer (2.5 mg PC/0.5 mL) while the other arm was treated with 0.5 mL of phosphate buffer. For the following two weeks this treatment regimen was continued but in addition, each of four corticosteroid formulations (containing (i) hydrocortisone 0.1%, (ii) clobetasone butyrate 0.05%, (iii) betamethasone 0.1% and (iv) clobetasol propionate, 0.05%) was applied to sites on both arms. 5 +/- 1 mg of each cream was applied twice daily to the sites on day 1, then once daily for a further four days; after two days of no application, the protocol was repeated. Estimation of pallor was usually made four times daily. At the end of the second week of corticosteroid application the blanching response to all four formulations on the PC treated arms was significantly higher than on the buffer treated arm. Tachyphylaxis to the applied corticosteroids was markedly less apparent on the lipid-treated arms. It is proposed that the applied phospholipid either supplements the lipid content of the skin or provides a thin film in intimate epidermal contact. Such a film may promote hydration of the stratum corneum and also provide an environment into which corticosteroids initially partition before a subsequent, more controlled, release to the underlying tissue. PMID- 2907574 TI - Concentration and time-dependent inter-relationships for cytotoxicities of nitrogen mustard drugs against lymphoblasts in-vitro. AB - Peripheral lymphoblasts were exposed either to different initial concentrations of the alkylating agents (melphalan, chlorambucil or phenylacetic acid mustard) using a fixed incubation time or a constant [3H]methylthymidine incorporation into the trichloracetic acid-insoluble fraction of the cells. The concentration time relationships were evaluated by calculating the amount of drug which had chemically reacted in the incubation system. Melphalan showed lower cytotoxicity at short exposure times and high drug concentrations, while chlorambucil exhibited higher cytotoxicity at longer exposure times. In the latter case the effect could be accounted for by the cytotoxic activity of monohydroxy chlorambucil which was formed in the incubation system. PMID- 2907575 TI - Effects of various ginseng saponins on 5-hydroxytryptamine release and aggregation in human platelets. AB - The effects of various ginseng saponins isolated from red ginseng roots, on aggregation and 5-hydroxytryptamine release (5-HT) human platelets have been investigated. Among the six saponins tested, only ginsenoside Rg1 inhibited adrenaline- and thrombin-induced platelet aggregation and 5-HT release dose dependently, at concentrations of 5 to 500 micrograms ML-1. Ginsenoside Rg1 had no effect on adrenaline- and thrombin-induced arachidonic acid release and diacylglycerol production. But it did reduce the elevation of cytosolic free calcium concentration (Ca2+)i shown in the second phase induced by adrenaline and thrombin, at concentrations of 10 to 500 micrograms mL-1. Those data suggest that the inhibitory effects of ginsenoside Rg1 on 5-HT release from, and aggregation of, platelets might be due to the reduction of (Ca2+)i elevation at the second phase induced by adrenaline and thrombin. The results suggest that ginsenoside Rg1 in red ginseng roots may be active as a drug in the treatment of artheroscleorosis and thrombosis. PMID- 2907576 TI - The effect of acute and chronic administration of morphine and morphine withdrawal on intestinal transit time in the rat. AB - The effects of acute and chronic morphine administration and of morphine withdrawal on intestinal transit time of a liquid meal were investigated using rats. Many experiments have assessed the effects of acute morphine administration on intestinal transit, but the intestinal effects of chronic morphine administration have been neglected. Our results showed no significant differences between morphine-dependent and control animals when assessing the leading edge of the liquid meal infusion, its distribution and geometric centre (G.C.). However, during naloxone-precipitated withdrawal from morphine, the leading edge of the infusion and its G.C. were significantly distal to values obtained from other groups. Acute morphine administration caused delayed intestinal transit of a meal infusion, an effect partly caused by significant retention of the infusion in the stomach and duodenum. The leading edge of the meal infusion and G.C. were significantly proximal to values obtained from other groups of animals. The results show that morphine-dependent rats develop complete tolerance to the delayed intestinal transit of a meal observed after acute morphine administration and that withdrawal from morphine accelerates intestinal transit of a liquid meal. PMID- 2907577 TI - Effect of alkylxanthines on gentamicin-induced acute renal failure in the rat. AB - Adenosine antagonists have been previously shown to be of benefit in some ischaemic and nephrotoxic models of acute renal failure (ARF). In the present study, the effects of three alkylxanthines with different potencies as adenosine antagonists 8-phenyltheophylline, theophylline and enprofylline, were examined in rats developing acute renal failure after 4 daily injections of gentamicin (200 mg kg-1). Renal function was assessed by biochemical (plasma urea and creatinine), functional (urine analysis and [3H]inulin and [14C]p-aminohippuric acid clearances) and morphological (degree of necrosis) indices. The various drug treatments produced improvements in some, but not all, measurements of renal function. However, any improvement produced by drug treatment was largely a result of a beneficial effect exerted by its vehicle (polyethylene glycol and NaOH). The lack of any consistent protective effect noted with the alkylxanthines tested in the present study indicates that adenosine plays little, if any, pathophysiological role in gentamicin-induced ARF. PMID- 2907578 TI - Activities of octopamine and synephrine stereoisomers on octopaminergic receptor subtypes in locust skeletal muscle. AB - The activities of the (-) and (+)- forms of p-, m- and o-octopamine and p- and m synephrine have been compared on the different subtypes of octopamine receptor present in the extensor-tibiae neuromuscular preparation from the locust hindleg. The rank order of potency of the (-)-forms on the OCTOPAMINE2A receptors was p synephrine greater than p-octopamine greater than m-octopamine greater than o octopamine greater than m-synephrine whilst the rank order of the (+)-forms was p synephrine greater than p-octopamine greater than m-octopamine. (+)-m-Synephrine and (+)-o-octopamine had no effect on this class of receptor when tested up to a concentration of 10(-3) M. The rank order of potency of the (-)-forms on the OCTOPAMINE2B receptors was p-synephrine greater than p-octopamine greater than m synephrine greater than m-octopamine greater than o-octopamine whilst the rank order of the (+)-forms was p-octopamine greater than p-synephrine greater than m octopamine greater than o-octopamine. (+)-m-Synephrine again had no effect up to a concentration of 10(-3) M. The rank order of potency of the (-)-forms on the OCTOPAMINE1 receptors was p-synephrine greater than p-octopamine greater than m synephrine greater than m-octopamine greater than o-octopamine, whilst the rank order of the (+)-forms was p-synephrine greater than p-octopamine greater than o octopamine greater than m-synephrine greater than m-octopamine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2907579 TI - Enantioselective metabolism during continuous administration of S-(-)- and R-(+) nicotine isomers to guinea-pigs. AB - The S-(-)- and R-(+)-nicotine isomers were administered subcutaneously via Alzet osmotic pumps to male Hartley guinea-pigs (n = 5 with each isomer) over a 23-day period. Estimated dosage rate throughout the experiment was 0.6 mg-1. Urine samples were collected over this time and the levels of urinary oxidative and N methylated nicotine metabolites were measured by cation-exchange HPLC analysis. S (-)-Nicotine formed only oxidative metabolites, whereas the R-(+)-isomer formed both oxidative and N-methylated metabolites. 3'-Hydroxycotinine and nicotine-1' oxide were major metabolites of both enantiomers; cotinine and nornicotine were only minor metabolites. The major N-methylated metabolite of R-(+)-nicotine was N methylnicotinium ion; N-methylcotininium ion and N-methylnornicotinium ion were also identified as metabolites of this nicotine isomer. Total N-methylated quaternary ammonium metabolites accounted for 15 to 20% of the administered dose of R-(+)-nicotine. An interesting enantioselective reduction in the percent of oxidative urinary metabolites formed S-(-)-nicotine was observed over 23 days. This may indicate the enantioselective induction of an uncharacterized metabolic pathway for this nicotine isomer. PMID- 2907580 TI - Postnatal behavioural effects of maternal nicotine exposure in rats. AB - The effects of nicotine on locomotor activity have been studied in neonate rats exposed to nicotine (1.5 mg kg-1 day-1) throughout the gestational period. Both 14 day old male and female offspring demonstrated an increase in spontaneous locomotor activity when compared with saline-exposed controls. However, systemic administration of (+)-amphetamine was effective in attenuating the hyperactivity of these nicotine-exposed pups. PMID- 2907581 TI - Orally administered kappa but not mu opiate agonists enhance gastric emptying of a solid canned food meal in dogs. AB - The effects of oral administration of selective mu (D-Ala2, N-Me-p-nitro-Phe4, Gly5-ol-DAGO, morphine) and/or kappa (3,4 dichloro-N-methyl N [2-(1. fyrrolidinyl) cyclohexyl]-benzene acetamide-U-50488, tifluadom) or mixed agonist (N-desmethyltrimebutine) opioid on gastric emptying have been evaluated using a radiolabelled [57Co] canned food meal in dogs fitted with gastric cannulas. In control conditions (placebo) the percentage of solids emptied 1 h after feeding was 27.3 +/- 4.1%. When given orally at doses of 0.01 to 0.5 mg kg-1, U-50488 increased significantly (P less than 0.05) by 29.1 to 60.8% in a dose-related manner (r-0.94, P less than 0.01) the amount of gastric emptying of the meal in 1 h. This effect was reproduced by oral administration of tifluadom (0.01 to 0.1 mg kg-1) and by N-desmethyltrimebutine (0.1 to 1 mg kg-1). In contrast, the gastric emptying was unaffected by DAGO and morphine at low doses (0.01 and 0.1 mg kg-1) but significantly (P less than 0.05) slowed with higher doses of morphine. The increases in amount of gastric emptying induced by tifluadom, U-50488 and N desmethyltrimebutine were abolished by previous administration of naloxone (0.1 mg kg-1 i.v.) and [(3-furylmethyl) noretazocine]-MR 22-66 (0.1 mg kg-1 i.v.). These results indicate that orally administered kappa, but not mu agonists at doses not exceeding 1 mg kg-1 enhance the amount of gastric emptying of a solid meal in dogs and suggest that this is due to a selective local stimulation of kappa mucosal or submucosal opiate receptors at antroduodenal level. PMID- 2907582 TI - Beta 2-adrenoceptor influences on the alpha 1- and alpha 2-mediated vasoconstriction induced by phenylpropanolamine and its two component enantiomers in the pithed rat. AB - Phenylpropanolamine (PPA, (+/-)-norephedrine) is commonly found in appetite suppressants and nasal decongestants. Within the cardiovascular system of the pithed rat, the drug and its two component enantiomers ((-)- and (+) norephedrine) are largely direct-acting agonists. The interaction between simultaneous alpha 1-, alpha 2- and beta 2-adrenoceptor mediated effects of the drug and its two enantiomers have been examined using the cardiovascular system of the pithed rat. On all adrenoceptors tested the potency was (-)- greater than (+/-)-, greater than (+)-norphedrine. The alpha 1- and alpha 2-mediated pressor responses of each were enhanced in the presence of the beta 2-adrenoceptor antagonist, ICI 118,551, and diminished in the presence of the selective beta 2 adrenoceptor agonist salbutamol. It is concluded that each form of the drug possesses the intrinsic ability to interact with the alpha 1-, alpha 2- and beta 2-adrenoceptors in the system used and that the interaction with those adrenoceptors determines the net increase in diastolic blood pressure that follows the intravenous administration of the compounds. These findings have a bearing on the recent controversy regarding the use of beta-blocking agents in the treatment of overdosage of the drug. PMID- 2907583 TI - Enhanced bioavailability of morphine after rectal administration in rats. AB - Plasma morphine levels and the area under the plasma concentration-time curve (AUC) after i.v. (10 mg kg-1), p.o. (100 mg kg-1) and rectal (unrestricted or restricted to 1.5 cm from the anus, 10 mg kg-1) administration of morphine hydrochloride were determined in 10 or 11-week-old male Wistar rats to compare bioavailability of morphine after the rectal dosage with that after oral administration. The AUC value after oral administration (15 micrograms min mL-1), which was normalized by the dose, was only one-tenth of that after i.v. dosing (151 micrograms min mL-1). In contrast, the AUC after rectal administration (unrestricted, 133 micrograms min mL-1; restricted, 142 micrograms min mL-1) was almost comparable with that after i.v. administration. From the comparison of these AUC values, the extent of systemic availability of morphine after rectal (unrestricted or restricted) and p.o. administration was estimated to be approximately 90 and 10%, respectively. PMID- 2907584 TI - Senna still causes laxation in rats maintained on a diet deficient in essential fatty acids. AB - The laxative effect of senna has been investigated in normal and essential fatty acid deficient (EFAD) rats. Oral administration of senna pod extract (7-5-90 mg kg-1) produced a dose-dependent increase in the number of soft faeces excreted by normal rats. Senna 30 mg kg-1 also reversed net absorption of water and increased the prostaglandin (PG) production in the colonic lumen of normal rats by about four times. Oral administration of senna pod extract to rats, maintained on a fat free diet for 30-90 days, produced diarrhoea and reversed net absorption of water as in normal rats. However, a fat-free diet reduced the PG production drastically in the colonic lumen both in senna-free rats and in senna-treated rats. In EFAD rats carrageenan oedema, but not dextran oedema, was also drastically reduced. Since PG mediation is not present in EFAD rats we conclude that the PG are not essential for laxation induced by senna and that water secretion and PG production in the rat intestinal lumen are unrelated. PMID- 2907585 TI - Reversal of neuroleptic-induced catalepsy by novel aryl-piperazine anxiolytic drugs. AB - The novel anxiolytic drug, buspirone, reverses catalepsy induced by haloperidol. A series of aryl-piperazine analogues of buspirone and other 5 hydroxytryptaminergic agonists were tested for their ability to reverse haloperidol induced catalepsy. Those drugs with strong affinity for 5 hydroxytryptamine1a receptors were able to reverse catalepsy. Drugs with affinity for other 5-HT receptors or weak affinity were ineffective. However, inhibition of postsynaptic 5-HT receptors neither inhibited nor potentiated reversal of catalepsy and leaves open the question as to the site or mechanism for this effect. PMID- 2907586 TI - [3H]8-OH-DPAT labels the 5-hydroxytryptamine uptake recognition site and the 5 HT1A binding site in the rat striatum. AB - The binding of [3H]8-hydroxy-2-(di-N-propylamino)-tetralin ([ 3H]8-OH-DPAT) to rat hippocampal and striatal membranes has been compared. In the hippocampus, low concentrations of [3H]8-OH-DPAT bound to a single, high affinity site which was sensitive to inhibition by spiperone, buspirone and ergotamine but not by mianserin, quipazine or (-)-propranolol. This is consistent with a selective labeling of the 5-HT1A receptor. In the striatum, [3H]8-OH-DPAT bound to two sites with high and low affinity (KD's 1.18 and 109 nM). The high affinity component was blocked by low concentrations of buspirone, spiperone and ergotamine. The low affinity component was blocked only by high concentrations of buspirone and spiperone, and was not displaced by ergotamine at concentrations up to 1 microM. The ergotamine-resistant component of striatal [3H]8-OH-DPAT binding was blocked by low concentrations of the 5-HT uptake inhibitors fluvoxamine and paroxetine, and by relatively low concentrations of 5-HT itself. Thus [3H]8-OH DPAT labels the 5-HT transporter in the rat striatum. Unlike [3H]imipramine binding, the binding of [3H]8-OH-DPAT to the 5-HT transporter was independent of external sodium ions. It is therefore suggested that 8-OH-DPAT acts as substrate for the 5-HT transporter and labels the 5-HT recognition site of the transporter complex. PMID- 2907587 TI - Effects of beclamide on isolation-induced aggression and locomotor activity in mice. AB - The anti-aggressive effects of orally administered beclamide (N-Benzyl-beta chloropropionamide) have been studied in male albino mice which were individually isolated for a 28-day period. Beclamide (50-250 mg kg-1 p.o.) caused an overall dose-dependent increase in the attack onset latency, a reduction in the percentage of animals attacking and the mean number of attacks/animal for this model of aggression. In addition, the highest dose of beclamide (250 mg kg-1 p.o.) did not significantly modify locomotor activity in mice. It was concluded that beclamide induced anti-aggressive effects at non-sedative doses. This anti aggressive action was thought be at least partially mediated, through a beclamide induced release of 5-HT from presynaptic sites. PMID- 2907588 TI - The influence of urotensin II on calcium flux in rat aorta. AB - The fish neuropeptide urotensin II (UII, 10 nM) caused a 51% increase in uptake of 45Ca by segments of rat aorta; this increase was abolished by the Ca channel blocking drug nitrendipine (200 nM). 45Ca efflux was unchanged in the presence of UII, but was significantly increased following washout of the peptide; again, this increase was not observed in the presence of nitrendipine. The results provide direct evidence that the nitrendipine-sensitive component of the contractile response of rat aorta to UII involves mobilization of extracellular Ca, with subsequent activation of a Ca-induced, Ca-release process intracellularly. The mechanisms responsible for the nitrendipine-resistant component of the contractile response to UII remain to be established. PMID- 2907589 TI - Amelioration of the hypotensive effect of trypanocidal diamidines by use of heavy soluble salts. AB - The influence of a heavy soluble dicaprylate salt preparation of a new trypanocidal diamidine (DiaPBF) on systolic and diastolic blood pressure and heart rate of rats has been compared with the effects of the easily soluble DiaPBF-dihydrochloride (DiaPBF-diHCl). After the dicaprylate the drop of the systolic blood pressure was 50% smaller than after an equimolar doses of DiaPBF diHCl. PMID- 2907590 TI - Somatostatin stimulates phosphodiesterase in rat anterior pituitary and brain, and GH4C1 cells. AB - Somatostatin administration to female rats increased the activity of calmodulin dependent soluble phosphodiesterase, both in pituitary and brain. This effect was also seen in homogenates of GH4C1 cells pretreated with the hormone. When assayed in the presence of EGTA no differences in rat brain and pituitary phosphodiesterase were observed between controls and somatostatin-treated, but when assayed in the presence of calcium or calcium plus calmodulin a clear increase in the activity of the enzyme was detected. In GH4C1 homogenates prepared from somatostatin-pretreated cells there was an increase in phosphodiesterase activity assayed in the presence of EGTA vs non-treated controls, which was more clear when assayed in the presence of calcium or calcium plus calmodulin. These observations suggest that somatostatin effects derive, at least in part, from increased cyclic nucleotide degradation. PMID- 2907591 TI - Application of a micro enzyme-linked immunosorbent assay (ELISA) to detection of anti-amebic antibody in various forms of amebic infection. AB - Techniques of a micro enzyme-linked immunosorbent assay (ELISA) used for the serodiagnosis of schistosomiasis were applied to amebic infection. Test sera were divided primary on the basis of serologic diagnosis and stool examination as follows; (I) gel diffusion precipitin test (GDP) positive and stool examination positive: 9 specimens, (II) GDP positive and stool examination negative: 29 specimens, (III) GDP negative and stool examination positive: 32 specimens. Virtually all of the individuals belonging to (III) were asymptomatic, while more than 75% of (I) and (II) were symptomatic. The upper limit of 99% critical range was calculated from the data of 70 serum specimens from healthy adult Japanese and was employed as the cut-off value. All of the specimens of (I) and (II) were judged positive by ELISA, generally with a much higher absorbance than the cut off value; whereas, approximately 80% of (III) were judged positive. The average absorbance of (III) was lower than that of (I) and (II). These findings suggest that the ELISA is well in accord with GDP qualitatively as far as GDP-positive individuals are concerned, and that even asymptomatic cyst carriers with negative serology by GDP may often be producing anti-amebic antibodies, although the titers are low. PMID- 2907592 TI - [Changes in urinary tubular enzymes and low molecular weight protein in diabetes mellitus]. PMID- 2907593 TI - Inhibitory effects of L-threo-DOPS, an L-noradrenaline precursor, on locus coeruleus-originating neurons in the caudate nucleus. AB - Electrophysiological studies using reserpine-treated cats were carried out to elucidate the effects of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) on the noradrenergic pathway from the locus coeruleus (LC) to the caudate nucleus (CN) neurons, which were activated by iontophoretically applied bromocriptine, a dopamine D-2 receptor agonist. In the CN neurons, glutamate-induced firing was inhibited by iontophoretic application of noradrenaline, but not by repetitive stimulation of the LC or iontophoretically applied L-threo-DOPS. After intraventricular administration of L-threo-DOPS, however, LC stimulation inhibited the glutamate-induced firing. These results suggest that L noradrenaline that was produced from the conversion of L-threo-DOPS inhibited the CN neurons which possess dopamine D-2 receptors. PMID- 2907594 TI - [Pilus type, hemagglutination titer and hemolysin production of Escherichia coli isolated from urogenital infections]. PMID- 2907595 TI - Highly increased levels of serum beta-hexosaminidase, arylsulphatase A and beta galactosidase in a patient with sepsis. PMID- 2907596 TI - Use of corrected retention indices based on 1-nitroalkane and alkyl arylketone scales for HPLC identification of basic drugs. AB - Sixteen basic drugs were examined by HPLC (gradient elution in acetonitrile/phosphate buffer, pH 3.2, containing 0.05% nonylamine) with six different ODS-silica columns. The retention indices (RI) were calculated with alkyl arylketone and 1-nitroalkane scales and were subjected to correction, which enabled comparison of results from commercially different column packing materials. The correction procedure was successful for the 1-nitroalkane scale. The scale based on alkyl arylketones was of less use for basic drugs, because some of them eluted earlier than the first reference homologue. This made impossible the proper calculation and correction of RI values for drugs such as cocaine, diphenhydramine, doxepin, and promethazine. The correction procedure of RI values calculated against the series of 1-nitroalkanes is recommended as a method of standardization of HPLC data. PMID- 2907597 TI - [Xamoterol]. PMID- 2907598 TI - Activation of macrophages by Entamoeba histolytica extracts in mice. AB - The effect of Entamoeba histolytica extracts on the production of inflammatory macrophages and the release of hydrogen peroxide (H2O2) and superoxide (O2-) from these cells was examined in C57BL/6 mice. Two different strains of E. histolytica, either virulent (IP:0682:1) or nonvirulent (DKB), were used in this study. The number of macrophages recovered from the peritoneal cavity of mice treated 5 days previously with 150 micrograms of either strain of amoebic extracts was significantly higher than in the saline-treated groups. Macrophages from mice treated with 150 micrograms of the IP:0682:1 strain of amoebic extracts exhibited a powerful burst of oxidative metabolis when triggered with phorbol myristate acetate (PMA). Extract from the non-virulent strain was much less effective in activating macrophages for the production of oxidative metabolites. Thus, a crude extract preparation from E. histolytica, particularly the virulent strain, induces a strong macrophage inflammatory response in which the cells also produce high levels of H2O2 and O2-. PMID- 2907599 TI - Molecular cloning and characterisation of the genes for a non-fimbrial adhesin from Escherichia coli. AB - A non-fimbrial adhesin (NFA-1) from the uropathogenic Escherichia coli strain 827 responsible for agglutination of human erythrocytes was cloned using the cos 4 cosmid vector. A clone was isolated which promoted haemagglutination and showed the same biological properties as the adhesin produced by the wild type strain. Both express adhesin at 37 degrees C, but not 18 degrees C nor in the presence of 1% glucose. Adhesin purified from the clone formed high molecular weight aggregates which were resolved to the 21 K dalton subunit protein seen in the wild type strain on denaturation. Binding to human kidney cells by the clone and the wild type E. coli, from which the genes were cloned, were compared in an ELISA assay and shown to be the same. The genes for the adhesin were isolated on a 15.5 kilobase BamHI-EcoRI fragment which was subjected to gamma delta mutagenesis. The NFA-1 operon was localised to a 6.5kb region of this fragment. PMID- 2907600 TI - A chromosomal integration system for stabilization of heterologous genes in Salmonella based vaccine strains. AB - We have developed a system whereby heterologous DNA encoding an antigen from an enteropathogen may be recombined into the chromosome of an attenuated Salmonella carrier strain. The system involves two steps: (i) integration of a hisOG deletion mutation into the chromosome; (ii) replacement of the hisOG deletion by the complete hisOG region and the segment of heterologous DNA which encodes the antigen of interest. Recombinants may be selected (his+). The system was used to integrate the genes encoding K88 fimbriae from enterotoxigenic Escherichia coli into the chromosome of a galE mutant of Salmonella typhimurium (LT2H1). Recombinants were detected at a frequency of between 1.0 x 10(-3) and 1.5 x 10( 3). A variety of tests confirmed that the K88 genes were integrated into the chromosome of LT2H1 and were expressed. The stability of the recombinant was tested both in vivo and in vitro. When administered orally to mice, the recombinant elicited a serum antibody response to K88, and retained the Salmonella vaccine potential of the vector strain. PMID- 2907601 TI - Study of the c-Ha-ras-1 locus polymorphism in an Italian population with high incidence of gastric cancer. AB - The c-Ha-ras-1 proto-oncogene locus is characterized by a restriction fragment length polymorphism resulting from length variation in a variable tandem repetition (VTR) region downstream from the structural part of the gene. The presence of uncommon alleles at this region has been suggested to be an informative marker for the development of different malignancies, including solid tumours. In order to identify possible genetic markers of cancer risk, we studied the c-Ha-ras-1 locus polymorphism in an Italian population characterized by a high incidence of stomach tumours. Gastric cancer patients, some having first degree relatives affected by the same malignancy, and control subjects were studied. A total of 176 DNAs was analysed by the Southern blotting technique with TaqI restriction enzyme. This yields a fragment containing the sequence of variable length (VTR) and also allows detection of a cleavage site polymorphism. Thirteen different alleles were detected and some new common and rare variants were found. Our results do not provide evidence that the inheritance of any allele may predispose to gastric malignancies. Segregation analysis carried out on 13 patients' families demonstrated, without exception, a Mendelian inheritance of patterns. PMID- 2907602 TI - Association study between Alzheimer's disease and restriction fragment length polymorphisms at the human amyloid beta protein gene locus. AB - Alzheimer's disease, an autosomal dominant disorder, is characterized by the presence of neurofibrillary tangles and senile extracellular plaques in the brain of affected individuals. An amyloid beta protein has been isolated from the core of these plaques, and the gene encoding this protein has been mapped to region q11.2 to q22.2 of chromosome 21. Independent linkage studies have shown that the locus responsible for familial Alzheimer's disease also maps to the long arm of chromosome 21. It is thus very tempting to speculate that a defect (or defects) of the amyloid beta protein gene is the cause of Alzheimer's disease. For this reason, we have done association studies between Alzheimer's disease and restriction fragment length polymorphisms of the amyloid beta protein gene locus. We report a study of six restriction fragment length polymorphisms at the human amyloid beta protein gene locus. Several haplotypes constitute very informative marker systems for this region of chromosome 21. One of the six polymorphisms, a 6.6/7.3 kb (kb = 10(3) base-pairs) EcoRI restriction fragment length polymorphism, is loosely associated with the presence of Alzheimer's disease in a population of 34 subjects. PMID- 2907603 TI - Late-onset Krabbe disease initially diagnosed as cerebroside sulfatase activator deficiency. AB - Clinical and biochemical findings in a male subject with progressive encephalopathy and peripheral neuropathy are presented. Early development was normal. At age 3.5 years, he had seizures associated with fever. Subsequently, there was progressive neurologic deterioration. A CT brain scan at age 4 years, 2 months demonstrated multiple areas of variable density in the white matter. There was mild slowing of nerve conduction velocities and a sural nerve biopsy revealed segmental demyelinative neuropathy. Metachromatic leukodystrophy was suspected, but arylsulfatase A activity in leukocytes and fibroblasts was in the normal range. The cerebroside sulfate loading test on intact cultured fibroblasts showed attenuated hydrolysis leading to a tentative diagnosis of cerebroside sulfatase activator deficiency. However, the attenuated response of proband fibroblasts was not normalized by supplementation with activator in a reproducible manner, and urine showed hyperexcretion rather than deficiency of activator. Ultimately, an assay for galactosylceramide beta-galactosidase activity established a deficiency of this enzyme leading to the diagnosis of late-onset Krabbe disease. PMID- 2907604 TI - Cloning of the PYR3 gene of Ustilago maydis and its use in DNA transformation. AB - The Ustilago maydis PYR3 gene encoding dihydroorotase activity was cloned by direct complementation of Escherichia coli pyrC mutations. PYR3 transformants of E. coli pyrC mutants expressed homologous transcripts of a variety of sizes and regained dihydroorotase activity. PYR3 also complemented Saccharomyces cerevisiae ura4 mutations, and again multiple transcripts were expressed in transformants, and enzyme activity was regained. A 1.25-kilobase poly(rA)+ PYR3 transcript was detected in U. maydis itself. Linear DNA carrying the PYR3 gene transformed a U. maydis pyr3-1 pyrimidine auxotroph to prototrophy. Hybridization analysis revealed that three different types of transformants could be generated, depending on the structure of the transforming DNA used. The first type involved exchange of chromosomal mutant gene sequences with the cloned wild-type plasmid sequences. A second type had integrated linear transforming DNA at the chromosomal PYR3 locus, probably via a single crossover event. The third type had integrated transforming DNA sequences at multiple sites in the U. maydis genome. In the last two types, tandemly reiterated copies of the transforming DNA were found to have been integrated. All three types had lost the sensitivity of the parental pyr3-1 mutant to UV irradiation. They had also regained dihydroorotase activity, although its level did not correlate with the PYR3 gene copy number. PMID- 2907605 TI - The human transforming growth factor alpha promoter directs transcription initiation from a single site in the absence of a TATA sequence. AB - Transforming growth factor alpha (TGF-alpha) is a transformation-responsive mitogenic polypeptide that is expressed in the brain, epithelial cells, and activated macrophages. We isolated and characterized the TGF-alpha promoter and localized the 5' end of the TGF-alpha transcript to a unique position. Surprisingly, no apparent TATA box was present in the promoter sequence, suggesting that transcription from mammalian genes can initiate at unique and specific positions from promoters lacking this sequence motif. PMID- 2907606 TI - Different structural alterations upregulate in vitro tyrosine kinase activity and transforming potency of the erbB-2 gene. AB - Compared with normal erbB-2 gp185, mutant erbB-2 proteins generated by mutations either in the transmembrane domain or by NH2-terminal deletion are able to transform NIH 3T3 cells at a 10- to 100-fold greater efficiency. Mutant proteins of both classes show increased tyrosine kinase activity, suggesting that an abnormal level of receptor-associated tyrosine kinase activity is a major determinant of erbB-2 oncogenic potential. PMID- 2907607 TI - Stimulation of spontaneous transmitter release at the frog neuromuscular junction by 12-O-tetradecanoylphorbol-13-acetate occurs in the absence of extracellular Ca2+ and is enhanced by depolarization. AB - The effect of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) on the release of transmitter at the frog neuromuscular junction has been investigated electrophysiologically. TPA (100 nmol/l) caused a gradual rise in miniature end plate potential (MEPP) frequency. After 20-30 min MEPP frequency had risen by approximately 40%. This action of the drug was not inhibited by bathing preparations in either Ca2+-free medium (0 Ca2+-1 mmol/l EGTA) or high Mg2+ medium, or by pretreatment with verapamil (5 mumol/l). The inactive TPA analogue 4-alpha-TPA had no effect on release rate. There was no indication of any positive correlation between resting MEPP frequency and the size of the subsequent response to TPA treatment. Any synergism between [Ca2+]i and TPA treatment is therefore likely to occur at a site other than that which determines spontaneous release rate. The stimulatory effect of TPA was enhanced 2-fold by carrying out the experiments in a partially depolarising saline (10 mmol/l K+). When TPA was applied to preparations bathed in Ca2+-free depolarising saline, the response to the drug was still significantly greater than that in non-depolarised preparations. It is concluded that responsiveness to TPA is enhanced by depolarisation, but that little, if any, of this enhancement can be attributed to the consequent influx of Ca2+. PMID- 2907608 TI - Evidence that SK & F 104078 does not differentiate between pre- and postjunctional alpha 2-adrenoceptors. AB - We have investigated the proposed postjunctional selectivity of the alpha 2 adrenoceptor antagonist SK & F 104078 employing the pithed rat, rat isolated atrium and human saphenous vein preparations. In the pithed rat, SK & F 104078 (5 mg kg-1) produced a 20-fold shift in the prejunctional ID50 (concentration of agonist producing 50% inhibition of the cardioacceleration to a single stimulus) and a 3-fold shift in the postjunctional ED50 (concentration producing 50% of maximum rise in diastolic blood pressure) of the alpha 2-adrenoceptor agonist xylazine. However, the alpha 2-adrenoceptor antagonist yohimbine also showed apparent selectivity for prejunctional receptors in the pitched rat. In the rat isolated atrium, yohimbine was approximately 10 times more potent than SK & F 104078 at enhancing the stimulation-evoked release of tritium in tissues preincubated with (3H)-noradrenaline. In the human saphenous vein, yohimbine and SK & F 104078 had pA2 values of 7.40 and 6.33, respectively, against contractions to noradrenaline, so that yohimbine was again approximately ten times more potent than SK & F 104078. In conclusion, SK & F 104078 behaved like yohimbine in its relative potencies at pre- and postjunctional alpha 2-adrenoceptors both in vivo and in vitro, so that we fail to find any selectivity of SK & F 104078 for postjunctional alpha 2-adrenoceptors. PMID- 2907609 TI - Alpha-1 and alpha-2 adrenoceptor agonists induce vasoconstriction of the normotensive rat caudal artery in vitro by stimulation of a heterogeneous population of alpha-1 adrenoceptors. AB - Although alpha-2 adrenoceptor agonists rapidly induce arterial vasoconstriction in vivo, such responses have proven difficult to obtain in vitro. We have investigated the vasoconstrictor effects of various alpha-1 and alpha-2 adrenoceptor agonists in the perfused superfused caudal artery of the normotensive rat. Intrinsic activities were; methoxamine; 1, phenylephrine; 0.94, noradrenaline; 0.93, guanfacine; 0.88, clonidine; 0.47, UK 14,304 [5-bromo-6-(2 imidazoline-2-ylamino)-quinoxaline tartrate]: 0.10, azepexole; 0. Antagonism by the selective alpha-1 agent, prazosin of the vasoconstrictor responses provoked by methoxamine, guanfacine or clonidine, showed a high affinity with--log KB values in the range of 8.5 to 9.4. There were no significant differences between the KB values obtained with the three agonists. Antagonism by the selective alpha 2 antagonist, yohimbine showed a low affinity with KB values between 6.7 to 7.6 for the three agonists. The calcium entry blocker, nicardipine, antagonized responses to clonidine at nanomolar concentrations and those to phenylephrine at micromolar concentrations. We conclude that vasoconstrictor responses in this isolated tail artery preparation are primarily mediated via an alpha adrenoceptor which can be classified, on the basis of the results with specific antagonists, as being of the alpha-1 type. The results obtained with nicardipine suggest that the population of alpha adrenoceptors is not, however, homogeneous. PMID- 2907610 TI - Probable involvement of vascular angiotensin II formation in the beta 2 adrenoceptor-mediated facilitation of the neurogenic vasopressor response in the pithed rat. AB - Rats were pithed, vagotomized and adrenalectomized and the effect of procaterol on the pressor response to electrical stimulation of the thoracolumbar preganglionic sympathetic outflow from the spinal cord or to exogenous noradrenaline was studied in the absence and presence of beta-adrenoceptor antagonists and drugs interfering with the renin-angiotensin system. 1. Basal diastolic blood pressure was decreased by captopril, ramiprilate (angiotensin converting enzyme inhibitors), saralasin (an angiotensin II receptor antagonist), pepstatin A (a protease inhibitor with renin antagonistic properties) and by functional nephrectomy (ligation of both renal hili), but was not affected by procaterol (a beta 2-adrenoceptor agonist), nebivolol (a beta 1-adrenoceptor antagonist) and ICI 118,551 (erythro-dl-1-(7-methylindan-4-yloxy)-3 isopropylaminobut an-2-ol; a beta 2-adrenoceptor antagonist). 2. The vasopressor response induced by electrical stimulation of the preganglionic sympathetic nerve fibres was increased by procaterol, whereas the increase in blood pressure evoked by exogenous noradrenaline was not affected. The pressor response to both electrical stimulation and exogenous noradrenaline was decreased by captopril, ramiprilate, saralasin and nephrectomy but was not affected by nebivolol and ICI 118,551. 3. The facilitatory effect of procaterol on the neurogenic, electrically induced pressor response, which was also obtained when basal blood pressure was decreased by nephrectomy and increased by Lys8-vasopressin, was abolished by ICI 118,551 but not affected by nebivolol. Under none of these experimental conditions did procaterol alter the vasopressor response to exogenous noradrenaline. 4. The facilitatory effect of procaterol on the neurogenic, electrically induced rise in blood pressure was abolished by captopril, ramiprilate, saralasin and pepstatin A.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2907611 TI - Morphine tolerance and nonspecific subsensitivity of the longitudinal muscle myenteric plexus preparation of the guinea-pig to inhibitory agonists. AB - 1. The sensitivity of the longitudinal smooth muscle/myenteric plexus (LM/MP) to agonists which reduce the amplitude of neurogenic contractions was studied in preparations obtained from animals implanted with either placebo or morphine (75 mg/pellet) pellets 7 days prior. 2. Tolerance or subsensitivity to morphine was observed following chronic treatment with morphine and was revealed as a rightward shift of the concentration-response curve to morphine. The degree of tolerance decayed modestly with time after removal from a morphine containing environment suggesting a time dependence for the loss of subsensitivity to morphine. 3. LM/MP preparations from animals pretreated with morphine also developed subsensitivity to the inhibitory effects of the purine analogue, 2 chloroadenosine. Subsensitivity to 2-chloroadenosine was seen as a parallel rightward shift of the concentration-response curve in morphine-tolerant preparations. The magnitude of the loss in sensitivity was comparable to that observed to morphine. 4. A reduction in sensitivity of the LM/MP following chronic treatment with morphine was also observed to the inhibitory effects of the alpha2 adrenoceptor agonists, clonidine and xylazine. In contrast to the results obtained with morphine and 2-chloroadenosine, the development of subsensitivity to alpha2 adrenoceptor agonists was characterized by a marked reduction in slope and a depression of the maximum response. 5. These data suggest that myenteric neurons possess spare receptors for morphine and 2 chloroadenosine but not for clonidine and xylazine. Furthermore, the studies support the idea that tolerance is associated with a general cellular change or adaptation which impacts on all of these inhibitory substances in such a way as to reduce their efficacy. PMID- 2907612 TI - Alpha 1-adrenoceptors of rat myocardium: comparison of agonist binding and positive inotropic response. AB - Binding of agonists to alpha 1-adrenoceptors labelled by 3H-prazosin was investigated in membranes of rat myocardium and compared to the inotropic response elicited by alpha 1-adrenoceptor activation on isolated right ventricles. 1. At 30 degrees C the full agonists, adrenaline and phenylephrine, displaced 3H-prazosin with a shallow inhibition curve. The data are compatible with the assumption that 32% of the binding sites were in a state of high affinity for the agonist adrenaline (KI 85 nmol/l) and 68% in a low affinity state (KI 1738 nmol/l). GTP transformed all binding sites into the low affinity form suggesting that at least some of the cardiac alpha 1-adrenoceptors are coupled to N-proteins. 2. At 0 degree C most of the binding sites (86%) were in a state of high affinity for agonists (KI for adrenaline: 91 nmol/l). 3. For several partial agonists and antagonists (cirazoline, methoxamine, indanidine (Sgd 101-75), oxymetazoline and phentolamine) no such distinct temperature- and GTP-shifts could be demonstrated suggesting a different kind of interaction with alpha 1-binding sites. 4. When temperature was changed during incubation with adrenaline, a rise of temperature (from 0 degrees C to 30 degrees C) converted high affinity sites into the low affinity form, whereas a decrease in temperature (from 30 degrees C to 0 degrees C) failed to induce the high affinity state for agonists. Short term incubation (0.5 min) with adrenaline at 30 degrees C resulted in significantly lower IC50 values as compared to equilibrium conditions at the same temperature.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2907613 TI - Transmitter release patterns of noradrenergic, dopaminergic and cholinergic axons in rabbit brain slices during short pulse trains, and the operation of presynaptic autoreceptors. AB - Slices of rabbit brain were field-stimulated either by single electrical pulses or by trains of 4 or 8 pulses at 1 or 100 Hz in order to study transmitter release patterns and the autoinhibition of transmitter release. The slices were preincubated with 3H-noradrenaline (cortex), 3H-dopamine (caudate nucleus) or 3H choline (caudate nucleus). Slices preincubated with 3H-noradrenaline were superfused with medium containing desipramine 1 mumol/l. The overflow of tritium elicited by single pulses amounted to 0.19% of the tritium content of the tissue. The overflow elicited by 4 pulses/1 Hz was similar, whereas that elicited by 4 pulses/100 Hz was 5.1-fold higher. Yohimbine 10-1000 nmol/l increased up to 2.5 fold the overflow evoked by 4 pulses/1 Hz but did not change the overflow evoked by single pulses or 4 pulses/100 Hz. - Slices preincubated with 3H-dopamine were superfused with medium containing nomifensine 1 mumol/l. The overflow of tritium elicited by single pulses was 0.39% of the tritium content of the tissue. The overflow elicited by 4 pulses/1 Hz was 1.3-fold and the overflow elicited by 4 pulses/100 Hz 1.4-fold higher. Domperidone 1-100 nmol/l and sulpiride 10-1000 nmol/l increased up to 2.4-fold the overflow evoked by 4 pulses/1 Hz but increased only slightly the overflow evoked by single pulses or 4 pulses/100 Hz. Slices preincubated with 3H-choline were superfused either with physostigmine free medium or with medium containing physostigmine 1 mumol/l. In physostigmine free medium, atropine did not increase the evoked overflow of tritium at any stimulation condition. In physostigmine-containing medium, the overflow elicited by single pulses was 0.18% of the tritium content of the tissue. The overflow elicited by 8 pulses/1 Hz was 2.0-fold and the overflow elicited by 8 pulses/100 Hz 2.2-fold higher. Atropine 2-200 nmol/l increased up to 2.4-fold the overflow evoked by 8 pulses/1 Hz but increased only slightly the overflow evoked by single pulses or 8 pulses/100 Hz. In physostigmine-free medium, sulpiride 10-1000 nmol/l did not change the single-pulse-evoked overflow of tritium in the absence but increased it in the presence of nomifensine 1 mumol/l. Single pulses elicit a large release of 3H-noradrenaline, 3H-dopamine and 3H-acetylcholine under the conditions of these experiments. Release elicited by single pulses is not subject to autoinhibition except for a small inhibition by spontaneously released transmitter in the case of dopaminergic and cholinergic axons.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2907614 TI - Fractional reduction of somatostatin concentration interacted with rat growth hormone releasing hormone to titrate the magnitude of pulsatile growth hormone and prolactin release in perifusion. AB - Growth hormone (GH) pulses in vivo are associated with increased hypothalamic portal growth hormone releasing hormone (GH-RH) concentration and can be prevented by GH-RH antisera. GH pulses are also associated with prior reduction of portal somatostatin (SRIF) concentrations, although SRIF antisera do not abolish GH pulses. In vitro, pulses of GH-RH as well as SRIF withdrawal are followed by pulses of GH release; the presence of GH-RH enhances post-SRIF GH release. We asked four questions: (1) During combined GHRH-SRIF exposure in vitro, must SRIF withdrawal be complete to produce a pulse of GH release, or is there a threshold diminution of SRIF which permits it? (2) When pulsatile GH release does occur, is it an all-or-none phenomenon, or is it titratable by fractional reduction of SRIF? (3) Does varying the GH-RH concentration while administering SRIF systematically alter GH release in response to fractional SRIF reduction? (4) Given a small but distinct effect of GH-RH on release of stored prolactin (PRL) in this system, does fractional SRIF reduction alter PRL release in parallel? Rat pituitary tissue whose hormone stores had been prelabeled with tritium was perifused for 120 min in combined 25 nM SRIF and 3 or 10 nM rat GH-RH (rGH-RH). Then, while maintaining rGH-RH concentrations, the SRIF concentration was left unchanged (control) or was reduced to 20, 15, 10, 5, or 0 nM for 60 min. Release of stored rGH and rPRL was assessed by immunoprecipitation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2907615 TI - Pressor response mediated via histamine H1-receptors of the guinea-pig sympathetic ganglia. AB - In pithed guinea-pigs, the general characteristics and origin of the pressor response to intravenous injection of histamine were examined. Histamine (5-80 micrograms/kg) produced a rapid, short-lasting, constant, prominent and dose dependent pressor response, followed by a secondary slight and prolonged depressor response. The vascular response to histamine was accompanied by a marked tachycardia. The pressor effect of histamine (30 micrograms/kg) was strongly reduced or abolished in animals pretreated with nicotine, reserpine, bretylium or 6-hydroxydopamine. Furthermore, pyrilamine, a histamine H1-receptor antagonist, antagonized in a dose-dependent manner the pressor response to histamine. On the contrary, metiamide, a histamine H2-receptor antagonist, as well as hexamethonium and atropine, cholinergic antagonists, did not suppress the pressor effect of histamine. The present experiments provide evidence that in guinea-pigs, the pressor component of the vascular response to histamine results predominantly from the activation of histamine H1-receptors in the sympathetic ganglia with consequent release of noradrenaline at postganglionic sympathetic nerve terminals. PMID- 2907616 TI - Specific D1 and D2 dopamine agonists have synergistic effects in the 6 hydroxydopamine circling model in the rat. AB - The effects of SK&F 38393, RU 24213 and quinpirole alone and the synergistic effects of a combination of both subtypes of dopamine agonist on circling behavior were studied in rats with a unilateral lesion of the nigro-striatal pathway. The ability of SCH 23390 and sulpiride to antagonize the synergistic effects induced by SK&F 38393 and RU 24213 in combination were also studied. Finally, the ability of these specific D1 and D2 dopamine antagonists to block the circling induced by two nonspecific dopamine agonists (apomorphine and amphetamine) was investigated. Some animals responded to only one of the selective dopamine agonists but all responded to apomorphine and to the combination of SK&F 38393 plus Ru 24213 or SK&F 38393 plus quinpirole. A powerful synergistic effect was able to antagonize these synergistic effects. The blocking capacity of SCH 23390 and sulpiride was highly diminished in the apomorphine induced circling model, compared to the amphetamine-induced circling model where normosensitive dopamine receptors are involved. These data suggest an heterogeneous responsiveness to D1, D2D1 plus D2 and mixed D1/D2 dopamine agonists and a strong synergistic effect of the combination of SK&F 38393 plus RU 24213, or SK&F 38393 plus quinpirole. Denervation also induced some changes in the ability of specific dopamine antagonists to block the behavioral response after the administration of non-specific dopamine agonists. PMID- 2907617 TI - Effect of GABAergic transmission in the subpallidal region on the hypermotility response to the administration of excitatory amino acids and picrotoxin into the nucleus accumbens. AB - Excitatory amino acids and picrotoxin have been shown to produce an intense stimulation of co-ordinated locomotor activity after bilateral administration into the nucleus accumbens of rats. The objective of this study was to determine the role of GABAergic neurotransmission in t he substantia innominata/lateral preoptic area in the hypermotility responses to excitatory amino acids and picrotoxin. It was found that the bilateral administration of muscimol into the substantia innominata/lateral preoptic area almost completely inhibited the stimulation of locomotor activity induced by the administration of alpha-amino-3 hydroxy-5-methylisoxazole-4-propionate (AMPA), kainic acid, N-methyl-D-aspartic acid and picrotoxin into the n. accumbens. In contrast, muscimol did not inhibit locomotor activity or induce catalepsy in control animals injected with saline into the nucleus accumbens. The inhibitory effect of muscimol on the hypermotility responses to excitatory amino acids and picrotoxin was not due to diffusion to the nucleus accumbens and the activation of GABAergic receptors at this site. This conclusion is preoptic area, which effectively inhibited the responses to AMPA and picrotoxin, were either much less effective or not effective in inhibiting these responses when injected into the nucleus accumbens. These observations suggest that the stimulation of locomotor activity produced by the injection of excitatory amino acids or picrotoxin into the nucleus accumbens may be mediated by the inhibition of a GABAergic neuronal pathway projecting from the nucleus accumbens to the substantia innominata/lateral preoptic area. PMID- 2907618 TI - [A ketamine-chlordemethyldiazepam combination in celioscopy]. PMID- 2907619 TI - Puberty. PMID- 2907620 TI - [Clinical and biochemical evaluation of the preparation aminoglutethimide]. PMID- 2907621 TI - [Diagnosis of genetic diseases using DNA recombination technics]. PMID- 2907622 TI - Development of a radioreceptor assay for the D2-selective dopamine agonist N 0437. AB - N-0437 is a recently developed dopamine (D2) agonist, theoretically attractive in the therapy of Parkinson's disease and glaucoma. Since its high potency allows small doses of the compound in clinical use and as extensive metabolism occurs in animals, a highly sensitive assay method was required for drug-monitoring purposes. To this end we developed a radioreceptor assay (RRA), a sensitive tool for the assessment of the sample's (dopaminergic) bioactivity. The RRA is based on competition between N-0437 and its tritium-labeled analogue for binding to dopamine receptors. The assay has been optimized for the preparation of the receptor suspension and the incubation conditions. Direct application of the assay for biological samples was impossible because of matrix interferences. Therefore, a solid-phase extraction method was developed in which the combination of a polar Si column and dichloromethane as eluent resulted in an effective elimination of the interferences. Recoveries were better than 90 and 95% for plasma and urine, respectively, even at concentrations at the determination limit of the method (300 pg/ml). Relative standard deviations were less than 15%. Because RRAs are stereoselective, the method discriminates between active and inactive species. PMID- 2907623 TI - Correlation of surface properties with conformational stabilities of wild-type and six mutant tryptophan synthase alpha-subunits substituted at the same position. AB - The surface properties of wild-type and six mutant alpha-subunits of tryptophan synthase substituted at the same position, 49, which is buried in the interior, were measured by surface tension, foaming and emulsifying properties to correlate the surface properties with the stabilities. The conformational stabilities of the seven alpha-subunits differed dramatically depending on the characteristics of the substituting residues [Yutani et al. (1987) Proc. Natl. Acad. Sci., 84, 4441-4444]. The mutant proteins substituted by isoleucine and phenylalanine in place of glutamic acid at position 49 were more stable than the other proteins and showed higher surface tension and lower foaming and emulsifying properties than the wild-type and other mutant proteins. Good correlations were observed between these surface properties and values of the Gibbs free energy of unfolding in water, of the proteins. This indicates that the surface properties of the alpha-subunits of tryptophan synthase depend closely on the conformational stabilities. PMID- 2907624 TI - Comparison of the antinociceptive effects of new [D-Arg2]-dermorphin tetrapeptide analogs and morphine in mice. AB - The antinociceptive effects of synthetic dermorphin tetrapeptide analogs containing D-Arg in position 2, H-Tyr-D-Arg-Phe-Gly-NH2 and H-Tyr-D-Arg-Phe-beta Ala-OH, were measured in mice by the tail-pressure test. The antinociceptive effect produced by intracerebroventricular (ICV), intrathecal (IT) and subcutaneous (SC) administration of either peptide was greater than that produced by morphine. Oral (PO) administration of the peptides showed approximately the same antinociceptive potency as morphine. In addition, the antinociceptive effect produced by SC and PO administration of either peptide was of longer duration than morphine. Pretreatment with naloxone resulted in nearly complete antagonism of the antinociceptive effects produced by ICV and IT administration of either peptide or morphine. Dose ratios (ICV/IT) of H-Tyr-D-Arg-Phe-Gly-NH2 and H-Tyr-D Arg-Phe-beta-Ala-OH, which were calculated from the AD50 (Antinociceptive Dose = 50% MPE) values, were 5.8 and 6.2, respectively, whereas that of morphine was only 1.46. These results suggest that the mechanisms of the antinociceptive effects of [D-Arg2]-dermorphin tetrapeptide analogs differ from morphine, and that these peptides may possess higher affinities than does morphine for opioid receptors in the spinal cord. PMID- 2907625 TI - Monoamine oxidase B; a misunderstood and misjudged enzyme. PMID- 2907626 TI - Pressor response to beta 1- and beta 2-blockers in conscious rats treated with phentolamine. AB - The purpose of this study was to examine the conditions whereby beta-blockers cause a pressor response in conscious, unrestrained rats: (1) whether beta blockers cause a pressor response in rats subjected to, or not subjected to, nonselective alpha-blockade with phentolamine; (2) whether the pressor response to beta-blockers is due to the blockade of vasodilator beta 2-adrenoceptors, and (3) whether it is due to an acute increase in the release of adrenaline (A) and noradrenaline (NA). In the first series of experiments cumulative dose-response curves for propranolol, atenolol and ICI 118,551, nonselective beta-, beta 1- and beta 2-selective antagonists, respectively, were constructed in rats subjected to a continuous intravenous infusion of phentolamine. The administration of each of the beta-antagonists caused a significant dose-dependent increase in mean arterial pressure (MAP). The ED50 values for the increase in MAP were found to be 3.6 +/- 0.8, 10 +/- 2.6 and 4.6 +/- 0.8 micrograms/kg for propranolol, atenolol and ICI 118,551, respectively. In the second series of experiments, a single bolus injection of a selective or nonselective beta-antagonist or saline vehicle was given to rats subjected to a continuous intravenous infusion of phentolamine. Plasma levels of A and NA were determined in the control condition, during the infusion of phentolamine and again after the injection of a beta-antagonist. The infusion of phentolamine significantly decreased MAP and increased plasma levels of A and NA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2907627 TI - Utilisation of benzodiazepines in a university hospital. PMID- 2907628 TI - The course of neuroleptic and antidepressant treatment in severe depressive illness. PMID- 2907629 TI - Sensorimotor and cognitive performance of schizophrenic inpatients treated with haloperidol, flupenthixol, or clozapine. PMID- 2907630 TI - Dyscognitive syndromes in neuroleptic therapy. PMID- 2907631 TI - Ionized calcium and neuroleptic-induced extrapyramidal symptoms. AB - In a prospective study, the association between neuroleptic-induced extrapyramidal symptoms (EPS) and serum calcium levels with special regard to ionized calcium was investigated. The sample included 24 newly admitted psychcotic patients who received neuroleptic treatment. The 11 patients in whom EPS developed had significant, lower ionized calcium levels in the drug-free period than the 13 patients without EPS. PMID- 2907632 TI - Does smoking reduce the risk of neuroleptic parkinsonoids? PMID- 2907633 TI - Adverse drug reactions with clozapine and simultaneous application of benzodiazepines. PMID- 2907634 TI - Cognitive functions in schizophrenic patients with tardive dyskinesia. PMID- 2907635 TI - Pharmacological properties of SDZ 208-912: a potential high potency, non classical neuroleptic. PMID- 2907636 TI - Does individually different sensitivity to dopaminergic stimulation determine the degree of tolerance and dependence to opioids? PMID- 2907637 TI - Conditioning of signs of a dopaminergic stimulation in rats. PMID- 2907638 TI - Relationship between residual symptomatology and auditory evoked potentials in schizophrenic outpatients. PMID- 2907639 TI - Recording automatic and controlled information processing by means of bioelectrical brain signals in normals and paranoid schizophrenics with and without neuroleptic medication. PMID- 2907640 TI - Topographic mapping of EEG and auditory evoked P300 in neuropsychopharmacology (topographic pharmaco-EEG and pharmaco-AEP 300). PMID- 2907641 TI - The problem of influencing specific or unspecific emotional states by drugs: effects of a tranquilizer and two beta-blocking agents under noise conditions. PMID- 2907642 TI - Resumption of benzodiazepine use after withdrawal in hospital--a follow-up study. PMID- 2907643 TI - Investigation of benzodiazepine-consumers concerning intake-habits, signs of abuse or dependence, and information about the drug. PMID- 2907644 TI - Ro 16-6028: a novel anxiolytic acting as a partial agonist at the benzodiazepine receptor. PMID- 2907645 TI - Predictors of neuroleptic treatment response in acute schizophrenia: results of a treatment study with perazine. PMID- 2907646 TI - The effect of OPC-4392, a partial dopamine receptor agonist on negative symptoms: results of an open study. PMID- 2907647 TI - The effect of the partial dopamine agonist terguride on negative symptoms in schizophrenics. PMID- 2907648 TI - Benzodiazepines for catatonic symptoms, stupor, and mutism. PMID- 2907649 TI - KC 9172 (free base of KC 7218)--an antipsychotic/anxiolytic compound. I. Antipsychotic and anxiolytic activity in comparison with chlorpromazine, clozapine, diazepam and buspirone. PMID- 2907651 TI - Zoological expeditions to the Krakatau Islands, 1984 and 1985. PMID- 2907650 TI - KC 9172 (free base of KC 7218)--an antipsychotic/anxiolytic compound. II. Discrimination from typical neuroleptics and benzodiazepine-like minor tranquilizers. PMID- 2907652 TI - Antibiotic-resistance patterns of soil bacteria (gram-negative rods) from the Krakatau islands (Rakata) and west Java, Indonesia, in 1984. PMID- 2907653 TI - Antibiotic-resistance patterns and relative concentrations of bacteria (gram negative rods) from ash deposits of various ages on the Krakatau islands. PMID- 2907654 TI - Antibiotic-resistance patterns of enteric bacteria of wild mammals on the Krakatau islands and west Java, Indonesia. PMID- 2907655 TI - Enteric bacteria of reptiles on Java and the Krakatau islands. PMID- 2907656 TI - Colonization of the Krakataus by bacteria and the development of antibiotic resistance. PMID- 2907657 TI - [Torticollis spasmodicus and addiction]. AB - From a random sample of 49 patients suffering from torticollis spasmodicus and dependence on alcohol or medicaments, 6 have been selected and are discussed with i view to findings possible mutual influences between the disorders. In particular, premorbid accentuation of personality presented itself as a potential risk factor leading to both tortocollis and alcoholism. In various cases, the patient makes use of alcohol for self-treatment of extrapyramidal-motor symptoms. But such phenomenological developments are preceded by varied constellations of conditions, that have to be taken into account in the treatment. PMID- 2907658 TI - Cytochemical localization and biochemical analysis of the enzyme markers in human hepatoma cell lines. AB - Three enzyme makers, glucose-6-phosphatase, ATPase and gamma-glutamyl transpeptidase, have been used in studying carcinogenesis of hepatocellular carcinoma. They have been investigated in animal models and human hepatocellular carcinoma in vivo and in vitro. But the inconsistent levels of these three enzymes associated with this type of carcinoma raised the possibility that the carcinoma cells might have derived from the cells originating from different stages of differentiation. To evaluate this possibility, three human cell lines, Hep G2, Hep 3B, and HA 22T, all thought to be arrested in different stages of differentiation based on their biochemical and morphological characteristics, were used as models. The three enzyme markers glucose-6-phosphatase, ATPase and gamma-glutamyl transpeptidase were examined cytochemically and biochemically. Our results showed that there was no correlation between the ATPase levels and the stages of the cell line's differentiation. But both glucose-6-phosphatase and gamma-glutamyl-transpeptidase were higher in cells that were more differentiated. PMID- 2907659 TI - [Changes in the symptomatological picture of schizophrenia in relation to the introduction of neuroleptics]. PMID- 2907660 TI - [The role of the endocrine system in memory disorders]. PMID- 2907661 TI - Chronic cocaine enhances defensive behaviour in the laboratory mouse: involvement of D2 dopamine receptors. AB - C57BL/6 male mice injected with a challenge dose (20 mg/kg) of cocaine 72 h after the end of chronic intermittent treatment with the psychostimulant (two daily injections of 20 mg/kg for 10 days) exhibited a clear-cut increase in defensive upright and sideways postures and escape when confronted with a non-drugged conspecific. Treated mice spent 40% of time showing defensive acts over the 5-min testing session. Administration of the selective D2 receptor antagonist (-) sulpiride (25 mg/kg) before the challenge dose of cocaine completely antagonized the increase in defensive behaviour, while the selective D1 receptor antagonist SCH 23390 (0.25-0.50 mg/kg) did not significantly affect defensive behavioural patterns. These results suggest the involvement of D2 receptors in cocaine induced hyperdefensiveness. The hypothesis that alteration in D2 receptor functioning produced by chronic cocaine administration may produce hyperdefensiveness possibly due to altered perceptive processes is discussed. PMID- 2907662 TI - Alpha 1- and alpha 2-adrenoreceptor antagonists differentially influence locomotor and stereotyped behaviour induced by d-amphetamine and apomorphine in the rat. AB - The importance of dopamine (DA) in mediating locomotor, exploratory and stereotyped behaviour in rodents is well established. Evidence also indicates a modulatory role for noradrenaline (NA) although, due to nonspecificity. of previously available agents, a precise role remains undefined. The effects of the specific and selective alpha-adrenoreceptor antagonists idazoxan (alpha 2) and prazosin (alpha 1) on behaviour induced by amphetamine and apomorphine have been investigated in the rat. d-Amphetamine (2 mg/kg) induced hyperactive locomotion and exploration. Pretreatment with prazosin (1 mg/kg) markedly reduced these responses. In contrast, pretreatment with idazoxan (20 mg/kg) only marginally altered d-amphetamine hyperactivity. Apomorphine (0.5 mg/kg) induced biphasic locomotor and exploratory activity. Neither alpha-antagonist affected the initial burst of activity (60 min), although prazosin inhibited whereas idazoxan potentiated the secondary phase (90-180 min). At higher dosage, amphetamine (6 mg/kg) and apomorphine (2 mg/kg) induced stereotyped behaviours. Prazosin pretreatment enhanced stereotyped gnawing and decreased sniffing and locomotion, whereas idazoxan increased locomotion and decreased amphetamine-induced mouth movements. These data indicate that DA-induced locomotor and stereotyped behaviours are differentially influenced (in opposite directions) by both alpha1- and alpha 2-adrenoreceptor antagonists. NA may thus modulate the expression and character of behaviour by influencing DA function in certain brain areas. PMID- 2907664 TI - [Treatment of insomnia and benzodiazepines]. PMID- 2907663 TI - Effects of anti-asthma drugs on PAF-induced death in mice. AB - A number of anti-asthma drugs was assayed for the ability to protect mice from platelet-activating factor (PAF)-induced death, which has been suggested to be dependent on the bronchoconstrictive features of this autacoid. Salbutamol, dexamethasone, theophylline, ketotifen and zindotrine, administered parenterally, produced a dose-dependent protection, while forskolin, enprofylline, disodium cromoglycate, nedocromil, azelastine and antagonists of acetylcholine, histamine and serotonin were devoid of protective effects. Theophylline, contrary to salbutamol, lost its protective effects in adrenalectomized mice, suggesting that these effects are dependent on the release of adrenomedullary cathecolamines. Salbutamol, theophylline and dexamethasone, at doses capable of inhibiting PAF induced death, did not affect PAF-induced haemoconcentration in mice, thus excluding widespread changes in vascular permeability as a major cause of death. These results are generally in agreement with the hypothesis that airway obstruction is an important determinant of PAF-induced death in mice. PMID- 2907665 TI - [Autonomic regulation of functions of the gastrointestinal system and various problems of pharmacotherapy]. PMID- 2907666 TI - [Entomologic study of a possible natural focus of arbovirus]. PMID- 2907667 TI - [Influence of endogenous catecholamines on responses of rat lung to beta adrenergic agonists]. AB - Relaxation responses to the beta-adrenoceptor agonists: isoprenaline (non selective), salbutamol (beta 2-selective) and noradrenaline (plus phentolamine 10(-5) M) (beta 1-selective) have been obtained on rat lung parenchymal strips in the absence and presence of pargyline and tropolone (monoamino-oxidase and catechol-O-methyltransferase inhibitors), cocaine (neuronal uptake blocking agent), corticosterone (extraneuronal uptake inhibitor) as well as in reserpinized rat. Responses to these beta-adrenergic agonists were not potentiated in the presence of any of these inhibitors. This indicates that endogenous catecholamines, enzymatic or uptake processes, do not modulate beta adrenoceptor mediated responses of rat lung strip and demonstrates that there is no correlation between neuronal uptake/beta 1-adrenoceptors and extraneuronal uptake/beta 2-adrenoceptor mediated responses, as had previously been suggested. PMID- 2907668 TI - Neuromediated action of beta-casomorphins on ion transport in rabbit ileum. AB - beta-casomorphins (beta-CMs) are opioid peptides derived from milk beta-casein. The beta-casomorphin analog beta-[DAla2,4, Tyr5] CM-5-NH2 reduced short-circuit current (lsc) and stimulated electrolyte absorption by an opioid effect in rabbit ileum in vitro. This effect was inhibited by 10(-7) M tetrodotoxin, 10(-6) M epinephrine and 10(-5) M naloxone. Atropine in the 10(-7)-10(-5) M range and 10( 5) M hexamethonium did not inhibit the action of the peptide on lsc. In comparison the muscarinic effect of 10(-3) M carbachol was inhibited by atropine in the 10(-8)-10(-5) M range. These results indicate that the action of the beta casomorphin analog was neuromediated and suggest that this peptide acted on the submucosal plexus located on the blood side of the intestinal epithelium. A physiological role of the food-derived beta-CMs peptides implies the passage of the active sequences from the lumen to the blood side of the intestine. PMID- 2907669 TI - Breathing pattern--gas exchange relation and acute effect of almitrine in severe chronic airflow obstruction. AB - Using a double-blind cross-over design, a single oral dose of 100 mg almitrine bismethylate and placebo were administered to 7 patients with chronic airflow limitation. In all patients, arterial blood gases at rest, ventilation and breathing pattern at rest and on exercise were measured before and 3 h after administration. Ventilation increased and PaCO2 decreased after almitrine; the mean PaO2 increase was statistically significant after active drug but the value increased more when tidal volume increased. It is concluded that in man the well documented improvement in the V/Q relationship after almitrine is in part related to a pure ventilatory effect though the possibility of increasing ventilation by mainly increasing tidal volume. PMID- 2907670 TI - [Alcoholic psychoses: therapeutic schemes]. PMID- 2907672 TI - Inflammation of the upper respiratory tract. Role of Pneumorel 80 mg. Proceedings of an international meeting. Athens, April 28-May 1, 1988. PMID- 2907671 TI - [Practical aspects of the clinical management of benzodiazepine dependence]. PMID- 2907673 TI - Efficacy of Pneumorel 80 mg (fenspiride) in the treatment of chronic sinusitis. Double-blind placebo-controlled study. PMID- 2907674 TI - Value of fenspiride (Pneumorel 80 mg) in the preoperative treatment of chronic open tympanum otitis. Double-blind placebo-controlled study. PMID- 2907675 TI - Value of Pneumorel 80 mg in the treatment of chronic otitis in adults. Multicentre study of 696 cases. PMID- 2907676 TI - Recent data on the pharmacology of fenspiride. PMID- 2907677 TI - Fenspiride and relaxation of tracheobronchial musculature. Mechanism of action. PMID- 2907678 TI - Efficacy of fenspiride in alleviating SO2 induced chronic bronchitis in rats and allergic rhinitis in guinea pigs. PMID- 2907679 TI - Mediators of inflammation and antagonism of experimental pleurisy in the rat by fenspiride. PMID- 2907680 TI - Management of NSAID-induced gastrointestinal lesions. AB - Mucosal lesions in the g.i. tract due to ASA and other nonsteroidal anti inflammatory drugs are well-known in clinical practice. Though the gastroduodenal mucosa is the area most commonly investigated, several recent reports focus on lesions in the small and large intestine as well. Despite considerable efforts in the field, none of the new substances developed in the past few years have proven convincingly superior to existing drugs. Instead, other approaches are being evaluated: Bypassing of the gastroduodenal mucosa through enteric coating and slow release formulations have been suggested, but the possibility of transferring the deleterious effects to distal parts of the gastrointestinal tract by such formulation modifications calls for extensive evaluation of this area, before these formulations can be applauded as advantageous in this group of patients. Co-administration of protective substances has also been advocated, and, despite somewhat contradictory results, protection has been reported by H2 antagonists alone or in combination with antacids, as well as by cytoprotective agents like Sucralfate, and prostaglandin analogues. PMID- 2907681 TI - Comparison between medical and elective surgical treatment of peptic ulcers. AB - During the last decades we have learnt how to treat chronic peptic ulcer disease both with surgery (mainly vagotomy) and with long term medical treatment (mainly H2-receptor antagonists) with great success and safety. Although much attention has lately been given to 'cytoprotective' agents, it is still too early to regard them as alternatives to acid reducing treatment in the long term management of severe peptic ulcer disease. The importance of campylobacter pylori for long term outcome is today only speculative. Only a few randomized studies have been performed comparing surgical and medical treatment. The hitherto published studies involve small numbers of patients or do not use an optimal dosage of the drug given. Nevertheless for most patients with severe peptic ulcer disease one can conclude that we have both medical and surgical alternatives of comparable efficacy and safety to choose among. The final decision if an elective operation or not should be performed must be based on the preference of the individual patient. PMID- 2907682 TI - Over the counter sales of histamine-2 receptor antagonists. AB - Self treatment with H2 antagonists may have a positive impact on quality of life and costs. It may, however, also lead to incomplete peptic ulcer healing with frequent relapse and complications, inadequate long term treatment, neglectance of the life style type treatment for gastroesophageal reflux disease and a delay in the diagnosis of gastric malignancy. More research needs to be focused on the consequences of a more unrestricted and symptom guided use of H2 antagonists. PMID- 2907683 TI - The origins of the AIDS virus. PMID- 2907684 TI - Investigational therapy in rheumatoid arthritis: a critical review. PMID- 2907686 TI - Isolation and partial characterization of rhizolysin, a high molecular weight protein with hemolytic activity, from the jellyfish Rhizostoma pulmo. AB - A new cytolysin has been isolated from the nematocysts of the jellyfish, Rhizostoma pulmo, and named rhizolysin. The hemolysin has a mol. wt of approximately 260,000, a sedimentation coefficient of 10.3 S and is rod-shaped with a calculated axial ratio of about 1:5. It appears to be composed of three subunits with a pI value near 7.8. Rhizolysin shows no phospholipase A activity, nor an induction period for its hemolytic activity and is completely inhibited by sucrose. The optimum pH was 6.75. The mu value calculated from the Arrhenius plot is 5940 cal/mole. Rhizolysin was inhibited by cholesterol and less by sphingomyelin. PMID- 2907685 TI - Effects of theophylline, beta-adrenergic stimulants and prednisolone on platelet and urine cyclic guanosine monophosphate (cGMP). AB - Experiments were carried out to investigate the effects of anti-asthma drugs on cGMP levels. In vitro, theophylline (5 X 10(-4) M) increased basal and 5 hydroxytryptamine stimulated cGMP formation by platelets (p less than 0.05) while salbutamol and prednisolone produced no change. No significant differences were found in urine cGMP levels in healthy subjects, after short term treatment with theophylline, isoprenaline or prednisolone. Urinary cGMP levels were lower than normal in the majority (7/10) of asthma patients tested and in female patients this difference was significant (p less than 0.05). Severity of asthma symptoms were not found to be associated with particular changes in urinary cGMP levels. Fluctuations in the cGMP levels were, however, greater (p less than 0.01) in asthma patients with a more unstable respiratory condition. The differences between in vitro and in vivo results may demonstrate that beta-stimulants and theophylline have different acute and chronic effects on cGMP formation, or show that in vivo these drugs primarily affect tissue enzymes that differ from those on platelets. PMID- 2907687 TI - Mosquito inoculation: an alternative bioassay for toxins. AB - Mosquitoes were evaluated as a bioassay host for several classes of biological toxins. Mosquitoes were sensitive to snake toxic or neurotoxic phospholipase A2 enzymes (but not to nontoxic phospholipase A2 enzymes), cobrotoxin, saxitoxin, microcystin and the scorpion insect sodium channel toxin. Mosquitoes were not sensitive to ricin, diphtheria toxin, anthrax toxin, botulinum toxin, tetanus toxin, conotoxin G or a scorpion sodium channel toxin toxic to mammals. Specific antisera neutralization tests with mosquitoes gave comparable results to those of a mouse assay. The mosquito is a suitable bioassay animal for many, but not all biological toxins, and offers a safer, more efficient and economical assay than mice. PMID- 2907688 TI - Separation and characterization of four different amino acid sequence variants of a sea anemone (Stichodactyla helianthus) protein cytolysin. AB - A basic protein cytolysin previously isolated from the Caribbean sea anemone Stichodactyla helianthus was shown by CM cellulose chromatography to consist of four isotoxins possessing different N-terminal amino acid sequences. These are designated as toxins I-IV in order of increasing isoelectric point. The estimated molecular sizes (17,400-18,200) of toxins I-III were very similar; toxins I and II posses one additional amino acid at their amino terminus relative to toxin III. Under denaturing conditions, toxin IV behaved as a significantly larger (19,600) polypeptide; Edman sequencing established that it possesses a seven residue extension at the N-terminal end relative to toxin III. None of the variants contained half-cystines or reducing sugars. Toxin III contributed 83% of the total purified cytolytic (hemolytic) activity, toxin II 14%, and the relatively insoluble toxins I and IV together only contributed about 3% of the total cytolytic activity. Cytolysin III lysed Ehrlich ascitic tumour cells, but when administered intraperitoneally in nonlethal doses to mice already inoculated with this tumour, it failed to protect the mice against the tumour. Comparison of the partial amino acid sequence of equinatoxin, another sea anemone protein cytolysin, with that of Stichodactyla cytolysin III indicates they are highly homologous. Many other cytolytic proteins isolated from sea anemones share these properties with Stichodactyla cytolysins: (1) selective inhibition of hemolytic activity by preincubation with sphingomyelin, (2) a molecular size of 10,000 20,000, and (3) an isoelectric point of 9 or above. PMID- 2907689 TI - Detection of Thy-1+ cells in the developing thymus of the lizard, Chalcides ocellatus. AB - The ontogenic appearance of Thy-1+ cells was studied in the thymus of the lizard, Chalcides ocellatus, by indirect immunofluorescence using a rabbit antibrain antiserum produced against surface determinants shared by both the thymus and the brain lizards. Thymic Thy-1+ cells were first detected at stage 37. They increased rapidly reaching adult numbers by stage 41. Apparently Thy-1+ cells differentiate from lymphoid precursors arriving at the thymus analage before stage 37. The results are compared to those found during the differentiation of Thy-1+ thymocyte in murine thymus and agree with former reports on the thymic development in Chalcides using rabbit antisera against adult thymocyte marker(s). PMID- 2907690 TI - Oncogenes take a place in pattern formation. PMID- 2907691 TI - The site of action of some selective graminaceous herbicides is identified as acetyl-CoA carboxylase. PMID- 2907692 TI - Eukaryote membrane genetics: the Fo sector of mitochondrial ATP synthase. PMID- 2907693 TI - Do multigene families regulate vertebrate development? PMID- 2907694 TI - Feedback control of transmitter release at the neuromuscular junction. PMID- 2907695 TI - Early intravenous beta-adrenoceptor blockade for victims of heart attack. PMID- 2907696 TI - Receptor-mediated control of neurotransmitter release from brain slices or synaptosomes. PMID- 2907697 TI - Sympathetic purinergic transmission in small blood vessels. PMID- 2907698 TI - How does adenosine inhibit transmitter release? PMID- 2907699 TI - Systemic manifestations of erucism: a case report. AB - Larvae of the caterpillar Thaumetopoea wilkinsoni are widely distributed in pine groves throughout Israel. Erucism is defined as urtication by Lepidoptera larvae. Both irritating effects on contact with skin and eyes and toxic effects on ingestion have been described after exposure to several species of Lepidoptera. We report the case of a 4-year-old child who vomited repeatedly and developed symmetrical swelling of both hands after touching a larva of Thaumetopoea wilkinsoni. PMID- 2907700 TI - [Comparative characteristics of the hemodynamic and antianginal actions of obzidan and albetol in patients with stenocardia]. PMID- 2907701 TI - [Blood serum proteins, IgA, IgG and IgM immunoglobulins and alpha 1-antitrypsin and alpha 1-antichymotrypsin in peptic ulcer treated with altramet]. PMID- 2907702 TI - [Changes in serum aspartate and alanine aminotransferase, lactate dehydrogenase, gamma-glutamyltransferase and creatine kinase activities and the myoglobin level during hemodialysis]. PMID- 2907704 TI - Studies on the optimal conditions for inactivation of Bordetella pertussis organisms with glutaraldehyde for preparation of a safe and potent pertussis vaccine. AB - The optimal conditions for inactivation of Bordetella pertussis organisms with glutaraldehyde for the production of a safe and potent whole cell pertussis vaccine were investigated. Two bacterial harvests from B. pertussis strain 10536 were treated with glutaraldehyde, each with 0.025, 0.05 and 0.1% concentrations of glutaraldehyde for 10, 60 and 120 min. The nine types of glutaraldehyde inactivated pertussis vaccine (GIPV) and conventional heat-inactivated pertussis vaccine (HIPV) preparations made from two bacterial harvests were comparatively evaluated for the mouse weight gain test (MWGT), potency, and the histamine sensitization (HS) and leucocytosis-promoting-factor (LPF) tests. The minimum period for killing the B. pertussis organisms with glutaraldehyde was greater than 10 min for 0.025%, 10 min for 0.05% and 5 min for 0.1% concentration. The average loss in opacity varied from 5 to 10% for GIPV preparations and was 14% for HIPV preparations. The GIPV preparations except those inactivated with 0.025% glutaraldehyde for 10 min (GIPV-A) were much less toxic than the HIPV preparations in the MWGT. The GIPV-A preparations did not pass the MWGT. The GIPV preparations were also much less toxic in HS and LPF tests than the HIPV preparation. The potency of GIPV preparations inactivated with 0.05% glutaraldehyde for 10 min (GIPV-D) was similar to that of HIPV preparations. The prolonged treatments with glutaraldehyde reduced the potency. The GIPV-D preparation with good potency and less toxicity was found to be inactivated with glutaraldehyde under optimal conditions. All the preparations were innocuous in the abnormal toxicity test. PMID- 2907703 TI - Multiple neuroectodermal abnormalities in pheochromocytoma patients. PMID- 2907705 TI - [Selective sensitivity of synaptosomal cyclases to glutamic acid]. AB - Electron cytochemical studies have been made of the effect of various concentrations of the glutamic acid on localisation of adenylate and guanylate cyclases in synaptosomes from the brain cortex of rats. It was found that the glutamic acid (10(-3) M) stimulates the activity of intrasynaptosomal adenylate cyclase, but does not affect postsynaptic pool of the enzyme. The effect of glutamate on guanylate cyclase results in the increase of the frequency of the reaction both in synaptosomal and postsynaptic membranes. It is suggested that in the conduction of glutamate signal, guanylate cyclase--cGMP, but not adenylate cyclase--cAMP, system may be involved, although activation of intrasynaptosomal adenylate cyclase indicates its participation in presynaptic processes. PMID- 2907706 TI - [Use of psychophysiologic indices for the prognosis of the clinical action of tranquilizers]. AB - A comprehensive comparative approach was used to assess the effectiveness of the psychophysiological indices as predictors of the effect of tranquilizing therapy with benzodiazepine drugs in neurotic patients. The study resulted in selection of several psychophysiological characteristics most relevant to the prognosis of individual responses to the tranquilizers irrespective of the particular neurosis form. The characteristics are recommended for the routine medical use. Indices of the sensorimotor activity and visual analyzer functional lability are among these. PMID- 2907707 TI - [Endogenous inhibitors of the specific binding of benzodiazepines in the cerebral cortex]. AB - The nature of inhibitors of [3H]-diazepam (D) specific binding (SB) was studied in 2 fractions of acidic extract from bovine brain cortex. Preparative high performance liquid chromatography (HPLC), mass spectrometry, UV and IR techniques identified hypoxanthine and inosine as inhibitors of SB D. These substances may participate in the neuronal activity control which is in part mediated by the benzodiazepine receptors. PMID- 2907708 TI - Gamma glutamyl transferase in diabetic rats. The effect of insulin treatment. AB - In rats, streptozotocin-induced diabetes resulted in the increase of plasma gamma GT. A daily dose of 2 U protamine zinc insulin for two weeks did not affect the high levels of both gamma GT and glucose. Supplementation with 3 U insulin for only one week reduced both gamma GT and glucose levels. This indicates that insulin treatment could correct the rise of the enzyme level found in some diabetic patients. PMID- 2907709 TI - Development of acellular pertussis vaccine in Japan. PMID- 2907710 TI - Memory effects of the combination of medazepam with nootropic agents. AB - Experiments were made on rats using step-through passive avoidance method to study the effect of the benzodiazepine medazepam (Mz) on the retention of the memory traces during tests on the 3rd hour, 24th hour and 7th day after training, as well as the influencing of this effect by the nootropic agents meclofenoxate (Mf), aniracetam (Anc) and Euclidan (Eucl.). All substances tested (Mz in a dose of 5 mg/kg weight, Mf - 100 mg/kg, Anc and Eucl - 50 mg/kg), applied both independently and in combination, were administered orally for six days prior to the training. Mz was found to impair the retention of the memory traces in all three tests. Meclofenoxate totally eliminated the memory-impairing effect of Mz. A marked antiamnestic effect of both Anc and Eucl was observed in similar experiments with scopolamine-induced (2 mg/kg i.p.) amnesia. Bearing in mind the results of other behavioural and biochemical studies, including radioligand tests, an attempt is made to justify the idea that the basic mechanism of the amnestic action of Mz is connected with the cerebral cholinergic neurotransmission. The results of the experiments using Opto-Varimex and Automex equipment for testing the effects of Mz, Mf, Anc and Eucl, and of the combination of Mz with the nootropic agents studied, on the spontaneous motor activity of the experimental rats, lead to the most general conclusion that Mz impedes the development of habituation, considered as a specific type of learning and memory process. To one degree or another, Mf, Anc and Eucl cancel this effect of Mz.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2907711 TI - The chronotropic effect of histamine, prometasin and cimetidin on rat heart. AB - The effect of histamine, prometasin (the blocker of histamine H-1 receptor) and cimetidin (the blocker of histamine H-2 receptor) on the frequency of the isolated right atrium of rat was studied. Histamine, prometasin and cimentidin were applied cumulatively in concentrations of 5.4 X 10(-6) to 16.3 X 10(-3) mmol/l so that each new concentration was 3.3 times higher than the preceding one. The positive chronotropic effect of histamine was shown to be strongest with a concentration of 5.4 X 10(-3) mmol/l. Prometasin and cimentidine applied in increasing concentrations gave a negative chronotropic effect. Prometasin and cimetidin applied in a concentration of 5.4 X 10(-3) mmol/l before histamine, decreased the positive chronotropic effect of histamine to more than 60% no matter whether prometasin and cimetidin were applied alone or together. This finding suggests that the effect of histamine on rat heart is mainly realized via histamine H-1 and H-2 receptors and partly through releasing catecholamines from the adrenergic nerve terminal. PMID- 2907712 TI - Effect of an original piperazine derivative of tetraline on the adrenergically mediated metabolic responses in cats and rats. AB - One piperazine derivative of tetraline (with code P11), possessing hypotensive and anti-hypertensive activity, is studied. Its alpha- and beta-adrenoceptor blocking properties are characterized by using indicators of adrenergically mediated metabolic responses in cats and rats. The parameters studied are: glucose and lactate in the blood, free fatty acids in the plasma and the activity of phosphorylase "a" in rat myocardium. The alpha- and beta-adrenergic properties of P11 are characterized by using adrenergic and dopaminergic agonists and antagonists (adrenaline, isoproterenol, phenylephrine, propranolol, phentolamine, apomorphine and pimozide) in the different experimental setups. Compound P11 studied inhibits the effect of phenylephrine on the glucose level in the blood of rats in a definite dose interval (1-4 mg/kg) which suggests that it possesses alpha-adrenoblocking properties. P11 decreases slightly the effects of isoproterenol or does not change these effects on the levels of glucose, lactate and free fatty acids in cats. There are no changes in the effect of adrenaline on the glucose content in rat blood and the isoproterenol-activated phosphorylase in rat myocardium is not inhibited. This gives grounds to assume that P11 possesses slight beta-adrenoblocking properties. From the analysis of the proper hyperglycaemizing action of P11 in rats in the 1-8 mg/kg dose range it may be assumed that dopamine-agonistic mechanisms are involved. PMID- 2907713 TI - Molecular approaches in the prenatal diagnosis and therapy of genetic disorders. AB - During the last decade a new class of DNA markers, the restriction fragment length polymorphisms (RFLPs), has been developed by molecular genetic techniques. Genetic linkage studies using RFLPs have resulted in a large number of chromosome assignments of genes, making possible prenatal diagnosis and presymptomatic testing in many genetic disorders. Even so, of the estimated 100,000 genes that comprise the human genome fewer than 2,000, or 2%, have been mapped. Studies of the molecular basis of some of these mutant genes have brought to light a remarkable multiplicity and diversity of mutations that produce relatively few clinical phenotypes. Many genetic disorders including the thalassemias, familial hypercholesterolemia, Tay-Sachs disease, cystic fibrosis, and congenital adrenal hyperplasia, have been shown to be genetically heterogeneous. It is necessary, therefore, to know the precise mutation in order to make accurate diagnosis and restore proper enzyme or gene function. PMID- 2907714 TI - Characterization of different forms of dipeptidyl peptidase IV from rat liver and hepatoma by monoclonal antibodies. AB - Nine monoclonal antibodies directed against DPP IV from rat liver plasma membranes were obtained. They recognized four different epitopes (A, B, C and D) of the enzyme. The epitopes A, B and C were located on the outside of the hepatocyte plasma membrane and were shared by DPP IV from hepatoma plasma membrane and the soluble form. Epitope D appeared to be partly inserted in the membrane and was found exclusively in the liver. Epitopes A, B and C and DPP IV revealed by histochemical means showed similar distribution patterns on frozen sections of various rat tissues, while epitope D did not show such a correlation. DPP IV is inserted in liver plasma membrane by two different mechanisms, one being phospholipase C-sensitive, while in hepatoma the enzyme is anchored in this membrane by a phospholipase C-resistant mechanism only. PMID- 2907715 TI - Characterization and clinical role of glomerular and tubular proteases from human kidney. PMID- 2907716 TI - Plasma membrane proteases as useful tool in histochemical toxicology. AB - Compared with mitochondrial, lysosomal and endoplasmic reticulum enzymes and plasma membrane-associated hydrolases plasma membrane-linked proteases in the rat thyroid gland, liver, kidney, placenta and yolk sac were more easily affected after the administration of the drugs salicylic acid and dexamethasone. Either a decrease or an increase of protease activity was observed in the surface membrane of capillary endothelial cells, hepatocytes, fetal placental cells and visceral yolk sac epithelial cells whereby proteases being localized in the same domain of the plasma membrane showed a different response. PMID- 2907717 TI - Radioautographic characterization of H1 and H2 receptor antagonists. Binding sites in rat gastric mucosal microcirculatory system. PMID- 2907718 TI - [Dermatoglyphic patterns in cryptorchism]. AB - Digital and palmar dermatoglyphic patterns of 155 children with cryptorchidy has been studied. Results were compared to two control groups of Spanish normal population. 50 and 300 males respectively, showing the following statistically significant differences: 1. High incidence of whorls (37.4% vs. 22.2% and 29.5%) and low frequency of ulnar loops (51.5 vs. 66.4 0 and 60.8%) on fingers. 2. Frequent recurrence of some digital patterns, with a higher frequency of accumulated whorls and lower frequency of accumulated ulnar loops. 3. Increased amplitude of atd angle. 4. No differences in finger ridge count or ab ridge count. PMID- 2907719 TI - [Caution in the interpretation of CD4 lymphocyte count after splenectomy in patients with HIV infection]. PMID- 2907720 TI - The H+ -ATP synthase of mitochondria in tissue regeneration and neoplasia. PMID- 2907721 TI - Regulation of the expression of cell cycle genes. PMID- 2907722 TI - [All-Union seminar "Methods of controlled screening of antibiotics and other biologically active substances"]. PMID- 2907723 TI - Influence of dopamine agonists and an opiate antagonist on agaricus-induced catalepsy, as tested by a new method. AB - A few drugs affecting the dopaminergic system were tested for cataleptic effects in mice, and compared with an orally administered plant extract, Agaricus Muscarius 30. Haloperidol, Agaricus, and a low dose of apomorphine (0.3 mg/kg) were cataleptic. Paralleling previously reported results with haloperidol, the Agaricus catalepsy was potentiated by the mixed agonist, apomorphine (5 mg/kg), and by the selective D2 agonist, bromocriptine (5 mg/kg) and was reversed by the D1 agonist, SKF 38393. Naloxone also reversed Agaricus catalepsy, suggesting an involvement of opiate as well as dopaminergic mechanisms. All conditions that produced catalepsy also suppressed spontaneous locomotion, except for Agaricus 30 given alone. These experiments also compared cataleptic drugs by the published "pinch" method that involves repeated trials with a new single-trial method. Catalepsy was produced by the same drugs in both tests, but the single-trial method was more sensitive for disclosing the catalepsy induced by weaker cataleptogens. PMID- 2907724 TI - Cardiovascular properties of a 5-HT1-like receptor agonist, 5-methoxy-3(1,2,3,6 tetrahydro-4-pyridinyl)-1H-indole (RU 24969) in normotensive anaesthetized rats. AB - Intravenous administration of the putative 5-HT1-like receptor agonist RU 24969 (10-1000 micrograms/kg) in anaesthetized rats induced a decrease in heart rate and blood pressure. The bradycardia was reduced, but not suppressed, by tertatolol, bilateral vagotomy or the combination of both treatments. The alpha 1 adrenoceptor blocking agent, AR-C 239, decreased the bradycardia induced by high doses of RU 24969. After treatment with hexamethonium, RU 24969 induced an increase in arterial blood pressure. The hypotensive response induced by RU 24969 was not altered by atropine. The hypotensive and bradycardic effects of RU 24969 were antagonized by methysergide (5-HT1-like receptor antagonist) and in part by spiroxatrine (5-HT1A receptor antagonist). Ketanserin (5-HT2 receptor antagonist) potentiated the effects of low doses of RU 24969. The cardiovascular effects of RU 24969 were antagonized neither by MDL 72222 nor by ICS 205-930 (5-HT3 receptor antagonists). The present results suggest that the cardiovascular effects of RU 24969 seem to be due to the stimulation of 5-HT1-like receptors. The participation of both 5-HT1A and 5-HT1B receptors subtypes has been considered. The results suggest a centrally-mediated inhibition of sympathetic tone and increase in vagal tone in the cardiovascular effects of RU 24969. PMID- 2907725 TI - Specific inhibition of adherence of an oral strain of Bacteroides gingivalis 381 to epithelial cells by monoclonal antibodies against the bacterial fimbriae. AB - Monoclonal antibodies against purified fimbriae from this organism blocked its adherence to buccal epithelial cells. Three clones of monoclonal antibodies against these fimbriae were selected for use. The isotype of the three was IgG1 kappa chain. The antibodies reacted with fimbriae or their partially dissociated oligomers, but not with their constituent monomers (43 K protein, fimbrilin) or with other B. gingivalis 381 components, in an enzyme-linked immunosorbent assay or by immuno-blotting. The antibodies agglutinated only B. gingivalis 381 cells and no other species of Bacteroides. The purified immunoglobulin G (IgG) antibodies inhibited bacterial adherence to the human buccal epithelial cells, but had no effect on bacterial haemagglutination to various animal and human erythrocytes. The papain-cleaved Fab fragment, which did not allow cell to cell cross-linking, also inhibited adherence of B. gingivalis 381 but did not interfere with haemagglutination. Thus the fimbriae of B. gingivalis 381 may be responsible for adherence to epithelial cells, which supports the notion that a different type of fimbria or a lectin-like protein may be acting as haemagglutinin in this bacterium. PMID- 2907726 TI - Use of a DNA probe in the diagnosis of adult polycystic kidney disease. AB - Adult polycystic kidney disease (APKD) is one of the most common inherited diseases in man. A diagnosis based on the demonstration of renal cysts with ultrasonography or computerised tomography may be inconclusive in early adulthood, the crucial years before child-bearing is complete. Here we describe the improved diagnostic probability that is possible using genetic linkage studies. A 24-year-old woman, whose father and younger sister were affected by APKD, was demonstrated to have a single cyst in each kidney. These findings were insufficient for a diagnosis of APKD and for this reason genetic linkage studies were undertaken. DNA was extracted from peripheral blood leukocytes from the presenting individual, and her immediate and extended family; the DNA was cut with the restriction enzyme PvuII, electrophoresed in a 0.7% agarose gel and blotted onto nitrocellulose before probing with a 32P-labelled 4 kb fragment. This contained DNA from the hypervariable region (3' hypervariable region, 3'HVR) that is linked to the gene for APKD on the short arm of chromosome 16 and has been used in other family studies by Reeders et al. We correlated the findings on Southern blotting with ultrasound evidence of APKD and found that the disease segregated with a 7.0 kb fragment in the presenting individual's father and sister. She was shown to have inherited this allele also; the use of this technique thus increased the probability of her having APKD from 50% to 96.5%. PMID- 2907727 TI - Quantitative structure-activity studies of beta-adrenoceptor blocking drugs to decrease ventricular arrhythmias in guinea pigs. AB - The correlations between the physicochemical properties (n-octanol-buffer partition coefficients, P) of two series of N-alkylated and ring alkylated beta adrenoceptor blocking phenoxypropanolamines and their antiarrhythmic activities were studied. For this purpose dose-response curves of the influence on the ventricular arrhythmia threshold (VAT) and on heart rate (HR) were determined in the anaesthetized guinea pig. The degree of N-alkylation correlated with the potency of the drugs to raise VAT and to lower HR. Intraventricular conduction was likewise depressed. Increasing ring alkylation did not consistently further increase biological activity. The combined data from series of drugs showed statistically significant parabolic correlations between hydrophobicity (log P' for pH 7.4) and the biological responses. It is concluded that the nonspecific antiarrhythmic and negative chronotropic activity of the investigated beta adrenoceptor blocking drugs largely depend on their lipophilic properties. In addition steric and pharmacokinetic factors may be operative. PMID- 2907728 TI - On the metabolism of ditazole in man. AB - This paper describes mass spectrometric studies on the metabolism of 4,5-diphenyl 2-bis-(2-hydroxyethyl)-amino-oxazole (ditazole, Ageroplas) in man. The metabolites were identified after cleavage of conjugates, extraction and derivatisation in urine of healthy volunteers orally administered with 400 mg of ditazole each. Besides the unchanged ditazole the following 7 metabolites could be detected: N-desalkyl and N,N-bisdesalkyl ditazole, hydroxy ditazole, N desalkyl-hydroxy and N,N-bisdesalkyl-hydroxy ditazole as well as benzil and hydroxy benzil. Therefore, two main metabolic pathways, the aromatic hydroxylation and the N-desalkylation, can be postulated. Ditazole and its metabolites (with the exception of benzil) are excreted in urine partly in a conjugated form. PMID- 2907729 TI - Archaebacterial ATPase: studies on subunit composition and quaternary structure of the F1-analogous ATPase from Sulfolobus acidocaldarius. AB - A modified procedure for the purification of soluble ATPase from the thermoacidophilic archaebacterium Sulfolobus acidocaldarius is described. In addition to (alpha) 65 and (beta) 51 kDa polypeptides, further subunits gamma * (20 kDa) and delta * (12 kDa) are demonstrated to be components of the enzyme, exhibiting a total molecular mass of 380 kDa. Molecular electron microscopic images of the native enzyme indicate a quaternary structure probably formed by the gamma *, delta *-complex as a central mass surrounded by a pseudohexagon of the peripherally arranged larger alpha and beta subunits. As can be derived from both molecular mass and electron microscopy data, the archaebacterial Sulfolobus ATPase emerges to exist as an alpha 3 beta 3-quaternary structure with respect to the larger subunits. This is normally found in typical F1-ATPases of eubacterial and eukaryotic organisms. Therefore it is postulated that F1- and F0F1-ATPases, respectively, can occur ubiquitously in all urkingdoms of organisms as functional units of energy-transducing membranes. PMID- 2907730 TI - Comparison of GST-P versus GGT as markers of hepatocellular lineage during analyses of initiation of carcinogenesis. PMID- 2907731 TI - [The expression of c-myb is strongly associated with the presence of estrogen and progesterone receptors in breast cancer]. AB - The c-myb gene was studied in 112 breast cancers. c-myb and estrogen receptor (ER) transcripts were found in 78 (70%) and 71 (63%) cancers respectively. Of these 71 ER positive cancers, 64 (90%) contained c-myb transcripts and of the 41 ER negative cancers, 27 (66%) did not contain c-myb mRNA. Our data show that c myb transcripts are strongly associated with ER and progesterone receptors (p less than 10(-4) status in breast cancer. Thus the c-myb expression could be associated with breast cancers of better prognosis and its analysis could allow a better characterization of new subsets of hormono-dependent cancers responding more efficiently to hormonotherapy. PMID- 2907732 TI - Novel phenoxyalkylamine derivatives. V. Synthesis, alpha-blocking activity and quantitative structure-activity analysis of alpha-[(phenoxyethylamino)propyl] alpha-phenylacetonitrile derivatives. PMID- 2907733 TI - Studies on 2(1H)-quinolinone derivatives as neuroleptic agents I. Synthesis and biological activities of (4-phenyl-1-piperazinyl)-propoxy-2(1H)-quinolinone derivatives. PMID- 2907734 TI - Severe exacerbation of psoriasis due to terfenadine. PMID- 2907735 TI - A method for comparing analgesics: glafenine and paracetamol. Multicenter cross over approach. AB - A double-blind multicenter cross-over study was conducted on 166 outpatients with painful chronic osteoarthritis of the hip and of the femoro-tibial joints, to compare the effectiveness of glafenine and paracetamol. Patients were randomly assigned to receive over a period of a week, either 400 mg of glafenine or 1000 mg of paracetamol twice a day at 8 a.m. and 4 p.m. in order to fill up the physical activity period during the daytime. This interval between tablet intake was chosen according to the design of the model. At the end of the week treatment period, patients crossed over. There was no wash out period between treatments. The following measurements: pain intensity (on Huskisson's visual analogue scale), functional index for hip and knee diseases, patients' overall opinion, patient preference, were evaluated at days 0, 7, 14. The results showed that both treatments produced effective analgesia but the improvement was significantly greater and observed in a larger number of cases when using glafenine rather than paracetamol. Fifty-one per cent of the nonresponsive patients to paracetamol could benefit from the glafenine treatment and 18 per cent of patients suffering from hip or knee osteoarthritis in this study showed improvement only with glafenine. Safety and biological tolerance were satisfactory with both drugs. PMID- 2907736 TI - The effects of median sternotomy and internal mammary artery takedown on sternal blood flow. PMID- 2907737 TI - Effect of subminimal inhibitory concentrations of pefloxacin on the piliation and adherence of E. coli. AB - Several recent reports have shown that sub-lethal concentrations of antibiotics may decrease the adhesive ability of bacteria to epithelial cells; however, the mechanism by which the antimicrobial agents reduce adherence has remained unknown. The effect of sub-MICs of pefloxacin, a new broad-spectrum antibacterial quinolone, was studied on: haemagglutination, adherence, outer membrane and fimbriae of a pyelonephritogenic E. coli strain. The strain agglutinated in a mannose-resistant way human P1 but not p erythrocytes. After purification, the fractions containing outer membrane and fimbriae proteins were studied using electron microscopy and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The E. coli strain, grown in the presence of sub-MICs of pefloxacin, exhibited: (i) abnormal forms with filament formation; (ii) a markedly altered capacity of haemagglutination (human P1 erythrocytes) and adherence to uroepithelial cells. The inhibition of haemagglutination and adherence corresponded to a decrease in P-fimbriae production. These results were also associated with changes in the extraction of the outer membrane proteins of pefloxacin-treated bacteria. No major qualitative difference could be seen in outer membrane and P-fimbriae protein profiles after growth with sub-MICs of pefloxacin. This study has demonstrated that sub-lethal concentrations of pefloxacin alter piliation and the outer membrane of E. coli. These changes are associated with reduced bacterial haemagglutination and adherence. PMID- 2907739 TI - The expression of rat homeobox-containing genes is developmentally regulated and tissue specific. AB - Seven rat homeobox-containing sequences have been isolated by screening a genomic library with a probe derived from a Drosophila antennapedia cDNA clone. The characterization of two of these homeobox-containing clones has been described (Falzon, M., Sanderson, N.D. and Chung, S. Y. (1987) Gene 54, 23-32). Sequence analysis of the remaining five homeobox regions reveals a 180 bp domain sharing 70-95% identity at the amino acid level with the homeodomain from the Drosophila antennapedia gene and with the homeodomains from other metazoan species. Genomic blot analysis shows that each of the homeobox-containing DNA segments is probably present in a single copy per haploid genome. Northern blot analysis of RNA transcripts indicates that the rat homeobox-containing sequences are expressed during embryogenesis and in newborn and adult tissues in a tissue-specific manner; RNA expression is predominantly detected in spinal cord and kidney. Moreover, the pattern of RNA transcripts observed is distinct for each homeobox sequence, indicating differential regulation. Among the seven rat homeobox containing sequences, the flanking sequences of five of the clones have no obvious sequence similarity with previously published sequences of homeobox containing genes from other species. Two of the rat clones have been identified as potential homologues to mouse homeobox-containing sequences. For both pairs, a high degree of amino acid conservation (greater than 95%) is observed within the homeodomain and its immediate flanking regions between the putative homologous genes in mouse and rat. This strengthens the assertion that some of the mammalian homeobox-containing genes encode highly conserved proteins and may serve important biological functions. PMID- 2907738 TI - Bis-arenoxypropanolamines as potential beta-adrenolytics: a reinvestigation. AB - A number of symmetrical as well as asymmetrical bis-arenoxypropanolamines have been synthesized and evaluated for their beta-adrenolytic properties. The pharmacological characterization of these compounds was performed in vitro by direct studies (3H-dihydroalprenolol was used as the specific ligand for beta receptors), and by determining the beta-blocking capacity on isoproterenol (ISO) induced increased heart rate (isolated guinea-pig atrium); and in vivo by evaluating the antagonism on ISO-induced hypotension and tachycardia, as well as the intrinsic sympathomimetic activity (ISA) on reserpinized and vagotomized rats. The best result was observed with the simplest derivative, i.e. the bis phenoxypropanolamine compound, which shows in vitro and in vivo potencies almost comparable to propranolol and, moreover, significant bronchodilating activity. PMID- 2907740 TI - Synthesis, structure and activity of a few open models related to classic H2 antagonists. PMID- 2907741 TI - Benzodioxanes and quinazolines: probes for characterizing alpha-adrenoreceptors. PMID- 2907742 TI - [Analysis of compensatory mechanisms of arterial hypertension in norepinephrine infusion]. AB - The NA infusion induced a raise in the AP, inhibition of sympathetic vasomotor activity and a drop in the heart rate in alert male cats. The hypertensive effect of the NA was weakening during first 90 min of the infusion, a complete inhibition of sympathetic activity persisted during the whole period of infusion as well as a decrease in the heart rate, in anesthetized cats. After deafferentation, the markedness of the arterial hypertension weakening decreased and the effect of the infusion on sympathetic activity and heart rate was abolished. Administration of pentamine during the infusion did not affect the AP in anesthetized cats, increased it in alert animals and decreased the AP in deafferented cats. The organism seems to have no humoral mechanisms of compensation of arterial hypertension induced with the 3-hr infusion of noradrenaline. PMID- 2907744 TI - [Beta-blockade therapy in heart failure. Rational bases of the interpretation of clinical data and clinical evidence in search of rational interpretation]. PMID- 2907743 TI - [Chronic treatment of dilated cardiomyopathy by beta blocking agents. Clinical and hemodynamic follow-up]. AB - symptomatic dilated cardiomyopathy were studied in order to evaluate the effect of long term sympathetic beta-blockade with metoprolol. Clinical evaluation, stress test, two-dimensional echocardiography, 24 hour ambulatory electrocardiography and hemodynamic assessment with Swan-Ganz catheter were performed before enrollment in the study. Patients were randomly assigned to the relative placebo (8 pts) or metoprolol group (12 pts) in a single-blind fashion. The placebo group received standard therapy (digitalis, diuretics, vasodilators and anticoagulants as needed), while the metoprolol group, along with standard therapy received low-dose beta-blockade, starting with 6.25 mg twice daily and then doubling every 4 days on the two daily administrations. The therapeutic end point was 100 mg. Patients received less than 100 mg if their systolic blood pressure was less than 100 mmHg or if their resting heart rate was less than 55 beats/min. Patients were clinically assessed every month and a 24-hour electrocardiography, echocardiography and hemodynamic control was repeated after six months. In the metoprolol group there was one sudden death and two drop outs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2907745 TI - [Modulation of alpha 1-adrenergic action by protein kinase C activity]. PMID- 2907747 TI - C4A7: a new variant of human complement C4. AB - A rare variant of complement C4 was found in 2 related individuals. It has the most anodic mobility found to date, no hemolytic activity detected by the overlay technique and a Bgl II RFLP pattern very similar to that of the C4A6 type. PMID- 2907746 TI - The baboon gene for apolipoprotein A-I: characterization of a cDNA clone and identification of DNA polymorphisms for genetic studies of cholesterol metabolism. AB - We have isolated and sequenced a baboon apolipoprotein A-I (ApoA-I) clone from a liver cDNA library using a human cDNA hybridization probe. This baboon cDNA contains the entire ApoA-I coding region (801 bp, 267 aa), a 3' untranslated region, and a poly(A)tail. Among comparisons with apoAI sequences from other species, the baboon cDNA is most similar to that of the cynomolgus macaque (99.2% homologous) and least similar to the rat sequence (72.6% homologous). A high frequency of nonsynonymous substitutions are observed by alignment of baboon and human apoAI cDNAs, but comparisons of hydrophilicity profiles show that protein structure is conserved by substitutions of aa with similar properties. A polymorphic PstI cleavage site was identified by Southern blot analysis and subsequently mapped to the 5' end of the baboon apoAI gene. To identify effects of apoAI allelic variation on cholesterol metabolism, we used immunoblotting to compare the distributions of ApoA-I among lipoprotein size classes in baboons from each genotype under basal and atherogenic diets. We observed an increase of ApoA-I in high density lipoprotein (size class 1) particles after atherogenic diets in homozygotes for one allele, as compared to slight decreases in the other genotypes. PMID- 2907748 TI - [Anxiolytic therapy. Dental applications]. PMID- 2907749 TI - Ergogenic effect of inhaled beta 2-agonists in asthmatics. AB - To investigate the effect of beta 2-agonists on exercise performance, eight asthmatics performed an incremental exercise test on a treadmill. Five minutes before the start of the exercise, they were treated with inhaled salbutamol or placebo in a double-blind manner. The exercise started at a low intensity (2 mph, 10% inclination), and every 3 min the speed was increased by 0.5 mph at the same inclination until the subjects were exhausted. Every minute peak expiratory flow, heart rate, blood lactate concentration, and rating of perceived exertion were measured. The same parameters were also measured following the completion of the exercise. No significant difference was seen in total working time, maximal lactate concentration, heart rate, or rating of perceived exertion, whereas the decrease in peak expiratory flow was reduced following pretreatment with salbutamol. It is concluded that the release of inhaled beta 2-agonists for use in competitive events is justified as no ergogenic effect was seen. PMID- 2907750 TI - Estimated membrane structure and receptor subtype selection of an opioid alkaloid peptide hybrid. AB - Preferred conformation, orientation, and accumulation of dynorphin A-(1-8) octapeptide, naltrexone, and N beta-(D-Leu-D-Arg-D-Arg-D-Leu-D-Phe)-naltrexamine (Lipkowsky et al., 1988) were estimated according to established procedures. Opioid binding site affinities and selectivities available from the literature were correlated with the estimated parameters of lipid membrane interaction. The results agreed with the molecular mechanism of opioid receptor subtype selection proposed earlier. PMID- 2907751 TI - Characterization of the receptor binding profile of (3H)-dermorphin in the rat brain. AB - Amphibian skin synthesizes a variety of biologically active peptides. Of these, dermorphin (Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2) is an extraordinarily potent opioid peptide up to 1000 times more active than morphine in inducing analgesia after intracerebroventricular administration. Dermorphin has little in common with the sequence of all hitherto known mammalian opioid peptides and is unique in having a D-amino acid residue in position 2. Specific binding properties of tritium labeled dermorphin were characterized in the rat brain. Scatchard or Hill analysis of equilibrium measurements performed over a large range of concentrations revealed a single population of dermorphin binding sites with a Kd value of 0.46 nM. Dermorphin and the selective mu-receptor ligand (D-Ala2, MePhe4, Gly5-ol)-enkephalin (DAGO) had similar high potencies in competing with (3H)-dermorphin binding, whereas the inverse holds for the prototypical delta receptor ligand (D-Pen2, D-Pen5)-enkephalin (DPDPE), which exhibited a potency three orders of magnitude lower. Dermorphin was tested for its relative affinity to mu and delta binding sites by determining its potency in displacing (3H)-DAGO and (3H)-DPDPE from rat brain membrane preparations. Based on these comparisons, dermorphin exhibited a selectivity ratio Ki(DPDPE)/Ki(DAGO) = 100, a value almost identical to that of DAGO, this ligand being considered as the protypical mu receptor probe. The high affinity and selectivity of (3H)-dermorphin together with its very low nonspecific binding make this peptide a useful tool for dissecting the role(s) of the mu-receptor(s). PMID- 2907752 TI - Structural and functional integrity of specificity and catalytic sites of trypsin. AB - The aspartic acid residue at the bottom of the substrate-binding pocket of trypsin was replaced by glutamic acid through site-directed mutagenesis. The wild type (Asp-189) and mutant (Glu-189) trypsinogens were expressed in E. coli, purified to homogeneity, activated by enterokinase, and tested on a series of fluorogenic tetrapeptide substrates. The substrates were of the general formula succinyl-Ala-Ala-Pro-X-AMC, where AMC is 7-amino-4-methylcoumarin and X is Lys, Arg, or Orn (ornithine). As compared to Asp-189 trypsin, the activity of Glu-189 trypsin on lysyl and arginyl substrates decreased by 3-4 orders of magnitude while its Km values did not significantly change. Lengthening the side-chain of Asp-189 by one methylene group could not be compensated for by shortening the side-chain of the substrate, since Glu-189 trypsin had no measurable activity on the ornithyl substrate. The replacement of Asp-189 with glutamic acid at the base of the substrate-binding pocket of trypsin appears to distort the structure of the critical transition-state complex. This could happen by disrupting interactions normally associated with Asp-189, and by altering the relative position of the scissile peptide bond in the active site of the enzyme. PMID- 2907753 TI - Differential effect of mixed D1/D2 and selective D2 dopaminergic antagonists on mouse T and B lymphocyte proliferation and interleukin production in vitro. AB - The effects of some dopaminergic antagonists were investigated on mouse lymphocyte proliferative responses in vitro. The mixed D1/D2 dopaminergic antagonists chlorpromazine, haloperidol and flupentixol inhibited 3H-Thymidine incorporation into adult BALB/c mouse spleen cells stimulated by concanavalin A, lipopolysaccharide from Escherichia coli, and allogenic cells in a mixed lymphocyte reaction. The inhibition was achieved at concentrations greater than 10(-6) M. It was not accounted for by decreased cell viability and it was no longer demonstrable when the compound was added 24 h or 48 h after the mitogenic stimulus. Conversely selective D2 dopaminergic antagonists sulpiride, metoclopramide and domperidone had no inhibitory effect at concentrations ranging from 10(-9) to 10(-5) or 10(-4) M. The three mixed D1/D2 antagonists inhibited the mitogenic effect of interleukin-1 on concanavalin A-stimulated thymocytes, but not the activity of interleukin-2 on the proliferation of the CTLL-2 cell line. The mixed D1/D2 antagonists interfered with the production of interleukin-2 but not with that of interleukin-1. These results indicate that dopaminergic antagonists may differentially affect lymphocyte proliferative responses to T or B cell mitogens or alloantigens. The mechanisms involved in terms of receptor specific or non specific phenomenons are discussed. PMID- 2907754 TI - Atypical alpha-adrenoceptor mediates phenylephrine-induced mydriasis in anesthetized cats. AB - Pupillary dilation and nictitating membrane (NM) contraction were elicited by pharmacological activation of alpha-adrenoceptors in vivo in anesthetized cats. A constant intravenous infusion of the alpha 1-adrenoceptor selective agonist phenylephrine (150 micrograms/min) was administered to produce a near maximal activation of both organs. Steady-state responses were attained about 15 minutes after starting the phenylephrine infusion. Administration of the alpha 1 adrenoceptor selective antagonist prazosin produced a dose-dependent blockade of NM contractions without altering phenylephrine-induced mydriasis when given as pretreatment (1.0 mg/kg i.v.) or post-treatment (0.01-1.0 mg/kg i.v.). In contrast, post-treatment with the alpha 1-adrenoceptor selective antagonist WB 4101 (0.1-1.0 mg/kg i.v.) or pretreatment with phenoxybenzamine (3.0 mg/kg i.v.) blocked both the NM and pupillary responses. These results suggest that the in vivo pupillary response to phenylephrine is mediated by an atypical alpha adrenoceptor that cannot be readily classified as an alpha 1- or alpha 2 adrenoceptor. In contrast, the alpha-adrenoceptors of the NM appear to be of the classical alpha 1 subtype. PMID- 2907755 TI - Genetic diversity and relationships of two pathovars of Pseudomonas syringae. AB - To determine genetic relationships within and between two pathovars of Pseudomonas syringae, strains typical of P. syringae pv. tomato (P. s. tomato) and selected strains of P. syringae pv. syringae (P. s. syringae) were characterized by three methods. DNA-DNA hybridization experiments showed that strains of P. s. tomato and P. s. syringae were, respectively, 86-100% and 37-47% homologous to DNA from a P. s. tomato reference strain when tested under stringent conditions. An analysis of electrophoretic variation in enzymes encoded by 26 loci placed 17 P. s. tomato strains studied in a group of four electrophoretic types, and these strains had a mean genetic diversity per locus of 0.076. Six P. s. syringae strains formed a second group of six electrophoretic types, which had a higher mean genetic diversity per locus of 0.479. The mean genetic distance separating P. s. tomato from P. s. syringae (D = 0.94) was unexpectedly large for strains of a single species. An analysis of restriction fragment length polymorphisms (RFLPs) with three cloned hybridization probes demonstrated that each of the P. s. tomato and P. s. syringae strains was unique. A method was developed to quantify the RFLP difference between pairs of strains, and cluster analysis revealed relationships among P. s. tomato, but not among P. s. syringae, that were similar to those based on enzyme polymorphisms. Implications of these findings for bacterial systematics and epidemiology are discussed. PMID- 2907756 TI - [Biochemistry of the pH maintenance mechanism and the proton pump of lysosomes]. PMID- 2907757 TI - [Growth of Clostridium perfringens in the guinea pig intestinal juice medium]. PMID- 2907758 TI - [Adult T-cell leukemia virus infection in hemodialysis patients and blood transfusion]. PMID- 2907759 TI - [The kinetics of endocrine cells of duodenal mucosa in rat]. PMID- 2907760 TI - [A case of ulcerative colitis associated with Takayasu's arteritis]. PMID- 2907761 TI - [The virulence factor of E. coli in genitourinary tract infections. 2. Detection of P fimbriae and its role in genitourinary tract infections]. PMID- 2907762 TI - [The virulence factor of E. coli in genitourinary tract infections. 3. Fimbrial specificity to genitourinary organs]. PMID- 2907763 TI - [Incidence of congenital anomalies associated with external genital anomalies]. PMID- 2907764 TI - Testicular function of scrotal testes after the cryptorchidectomy in dogs with unilateral cryptorchidism. PMID- 2907765 TI - Population shift between piliated and non-piliated bacteria in various culture conditions of Corynebacterium renale. PMID- 2907766 TI - [Malignant pheochromocytoma of both adrenals combined with sympathetic nervous system tumors of the small intestine]. PMID- 2907767 TI - [Use of the ELISA test for detection of toxins of Clostridium perfringens type A]. PMID- 2907768 TI - Monoclonal antibodies to K88ab, K88ac and K88ad fimbriae from enterotoxigenic Escherichia coli. AB - K88ab, K88ac and K88ad fimbriae derived from enterotoxigenic Escherichia coli strains involved in porcine colibacillosis were used to immunize BALB/c mice. Several hybridomas secreting monoclonal antibodies (MAbs) against the three intact K88 fimbriae subtypes were produced by fusion of spleen cells from these mice with P3-X63-Ag8.653 myeloma cells. Hybridomas producing MAbs with affinity for all 3 E. coli K88 subtypes proved to be the most frequent (248/303), but subtype-specific monoclonals (39/303) as well as MAbs reacting with two but not with the third subtype (16/303) were also produced. The antibody-containing culture supernatants from 71 selected hybridomas were characterized by enzyme linked immunosorbent assay (ELISA) titrations, ELISA inhibition experiments and further examined by immunoblotting. Derivation of several MAbs specific for one of the E. coli fimbrial antigens, K88ab, K88ac or K88ad, was of interest in view of the extensive sequence homology in their primary structures. Specific binding of the MAbs to fimbriae on the surface of K88-positive E. coli strains was indicated by agglutination tests and visualized by immuno gold labeling and electron microscopy. The present MAbs against K88 fimbriae have potential veterinary applications for diagnosis and treatment of porcine colibacillosis. Preliminary results indicate the therapeutic value of oral administration of murine ascitic fluid containing anti-K88 MAbs to piglets experimentally infected with E. coli K88. PMID- 2907769 TI - The causal agent of halo blight in bean, Pseudomonas syringae pv. phaseolicola, attaches to stomata via its pili. AB - The phytopathogenic pseudomonad Pseudomonas syringae pv. phaseolicola causes halo blight of bean (Phaseolus vulgaris L.). Initiation of infection depends on the ability of the cells to adhere to the target cell surface. P. syringae pv. phaseolicola expresses pili, which are the receptors of the lipid-containing dsRNA bacteriophage phi 6. phi 6-resistant bacterial strains can be divided into different piliation types. It was possible to show that the adhesion of the bacteria onto plant cell surface was dependent on the pili. Non-piliated bacterial stains showed a much lower adherence to the leaf surface than strains expressing phi 6 specific pili. Scanning electron microscopy showed that the piliated bacteria attached to the leaf surface at the site of stomata. Non piliated bacteria were evenly distributed on the leaf surface. All bacterial strains used in this study were capable of causing halo blight if injected into the plant. If the bacteria were sprayed on the plants, followed by spraying of sterile buffer, only piliated bacteria caused symptoms. PMID- 2907770 TI - Location of adhesion sites for P-fimbriated and for 075X-positive Escherichia coli in the human kidney. AB - High-affinity binding sites for P-fimbriated and for 075X-positive Escherichia coli were located in the human kidney. Frozen sections of normal human kidney were double-stained first with fluorochrome-labelled bacteria and then with fluorochrome-labelled nephron site-specific lectins or antibodies. The P fimbriate recombinant E. coli strain used showed specific adherence to glomerular structures, to the lumen of proximal and sital tubules and to vascular endothelium but did not adhere to collecting ducts or to peritubular sites. Two E. coli strains having the 075X adhesin showed specific adherence to renal interstitium, to glomerular elements and to Bowman's capsule. The method described allows the detailed determination of tissue-substructure specificity of bacterial adhesion. Our results demonstrate tissue tropism in the adhesion of E. coli to human kidneys and suggest a pathogenetic role for X adhesins. PMID- 2907771 TI - Fimbrial phase variation and systemic E. coli infection studied in the mouse peritonitis model. AB - Mouse peritonitis induced by intraperitoneal injection of a virulent (LD50 4 x 10(5) E. coli 018:K1:H7 strain isolated from neonatal meningitis was studied. These bacteria are capable of producing both type 1 and S fimbriae, binding to mannose or sialic acid containing glycoconjugates, respectively; the production of both fimbrial types is subject to phase variation. A broth culture of the bacteria was fractionated into subpopulations containing either type 1 or S fimbriae or neither (nonfimbriated cells), and each fraction, grown in broth to logarithmic growth phase, was used to infect groups of mice. The type 1 fraction was associated with decreased virulence as the fraction was eliminated rapidly without causing a progressive infection even at 10(6) bacteria/mouse, whereas both S and nonfimbriated cells started rapid multiplication in the peritoneal cavity and spread to the blood. In nonfibriated cells, however, S fimbriae production was induced at the same time so that at 1 h after injection, 60-70% of the bacteria in the peritoneal cavity and in the blood of the mice had S fimbriae. The injected S-fimbriated fraction remained completely S-fimbriated. Rapid induction of S fimbriae also took place in vitro when the nonfimbriated bacteria were grown in mouse serum or peritoneal fluid. Anti-S serum protected the mice from a lethal dose of S-fimbriated bacteria. PMID- 2907772 TI - Amino groups in Clostridium perfringens epsilon prototoxin and epsilon toxin. AB - Modification with succinic anhydride (SA) of Clostridium perfringens epsilon prototoxin or toxin resulted in a loss of activation by trypsin or lethal activity, respectively. The prototoxin was more sensitive to succinylation than the toxin. On the other hand, the succinylated prototoxin was activated and cleaved by chymotrypsin, but not by trypsin. The lethal activity of the toxin was also lost after treatment with 2,3-dimethylmaleic anhydride (DMA) or 2,4,6 trinitrobenzenesulfonic acid (TNBS). When the DMA-treated toxin treated with SA or TNBS was incubated under acidic condition, it regained lethal activity. Thus modification of amino groups (lysine residues) prevented activation of the prototoxin by trypsin, and abolished lethal activity of the toxin. PMID- 2907773 TI - Influence of cloned Escherichia coli hemolysin genes, S-fimbriae and serum resistance on pathogenicity in different animal models. AB - The virulence of the uropathogenic E. coli strain 536 (O6:K15:H31) which produces the S-fimbrial adhesin (Sfa+), is serum-resistant (Sre+) and hemolytic (Hly+) and its derivatives were assessed in five different animal models. Cloned hemolysin (hly) determinants from the chromosomes of O6, O18 and O75 E. coli strains and from the plasmid pHly152 were introduced into the spontaneous Sfa-, Sre-, Hly- mutant 536-21 and its Sfa+, Sre+, Hly- variant 536-31. As already demonstrated for the 536-21 strains (Infect. Immun. 42: 57-63) the O18-hly determinant but not the plasmid-encoded hly determinant of pHly152 transformed into 536-31 contribute to lethality in a mouse peritonitis model. Similar results were obtained with both Hly- host strains and their Hly+ transformants in a chicken embryo test and in a mouse nephropathogenicity assay in which the renal bacterial counts were measured 15 min to 8 hours after i.v. infection. S-fimbriae and serum resistance had only a marginal influence in these three in vivo systems. In contrast all three factors, S-fimbriae, serum resistance and hemolysin, were necessary for full virulence in a respiratory mouse infection assay. In a subcutaneously induced sepsis model in the mouse restoration of S-fimbriae and serum resistance and separately chromosomally-encoded hemolysis increased virulence to a level comparable to that of the parental 536 strain. PMID- 2907774 TI - [Neurotransmitters as intracellular mediators during embryo development]. PMID- 2907775 TI - Speciation of organisms within the Mycobacterium avium-Mycobacterium intracellulare-Mycobacterium scrofulaceum (MAIS) complex based on restriction fragment length polymorphisms. AB - A DNA probe which hybridizes to all pathogenic species of slow-growing mycobacteria has been used to identify restriction-fragment-length-polymorphisms (RFLPs) in Bam Hl digests of chromosomal DNA from members of the Mycobacterium avium-Mycobacterium intracellulare-Mycobacterium scrofulaceum complex. The RFLP patterns so produced were found to fall into distinct categories which were representative of each of the three species. Except for two doubtful isolates, strains of M. avium were found to fall into two related RFLP-types, one of which contained the vast majority of the strains tested. In contrast, M. intracellulare strains were found to be more heterogeneous. For these strains, we found one major RFLP-type and one subsidiary type which appears to be a sub-set of the first. We also found two further RFLP-types which contained serovars 7 and 18 respectively. We conclude from this that M. avium, M. intracellulare and M. scrofulaceum are three distinct species and that serovars belonging to the 'intermediate group' of Meissner and Anz belong to the species M. avium. Utilizing these criteria, we examined a number of isolates from the 'ambiguous' serovar 9 and found that of eight strains tested, six typed as M. avium and two typed as M. intracellulare. PMID- 2907776 TI - Detection of yellow fever virus nucleic acid in infected mosquitoes by RNA:RNA in situ hybridization. AB - An in situ hybridization technique was developed for the strand-specific detection of yellow fever virus (YFV) RNA. An 35S-labeled, transcribed RNA probe was used to detect positive-sense polarity YFV genomic RNA in infected C6/36 (Aedes albopictus) cells, dissected mosquito tissues, and sections of plastic embedded, YFV-infected Aedes aegypti mosquitoes. Mosquito tissues fixed in buffered Formalin retained morphological integrity. The low concentrations of probe used yielded high specific signal on infected specimens and low background signal on uninfected specimens. PMID- 2907777 TI - Some quantitative EEG findings in unmedicated and medicated major depressives. AB - To confirm previous quantitative EEG findings in major depressive disorder and to assess effects of medication, EEGs were recorded under eyes closed and open conditions in 68 patients (34 unmedicated and 34 medicated) and nonpatients matched for age and sex. Time series analyses of amplitude, frequency and wave symmetry were performed; differences between eyes open and closed were adjusted for eyes closed values to obtain measures of reactivity. These reactivity measures yielded the main differences between unmedicated patients and nonpatients; depressives were more reactive. Reactivity differences were eliminated or reversed in medicated patients. The EEGs of unmedicated depressives appear to be overreactive, while medications decrease EEG reactivity. PMID- 2907778 TI - [Onset and duration of action times for the new muscle relaxants vecuronium and atracurium. Comparison with pancuronium]. PMID- 2907779 TI - [Behavior of neuromuscular blockade parameters in response to vecuronium]. PMID- 2907780 TI - [Behavior of intraluminal gastrin and somatostatin in subjects with type II diabetes mellitus]. PMID- 2907781 TI - Polyamines in cerebral ischemia. AB - The present series of experiments was designed to study regional profiles of polyamines (putrescine, spermidine, and spermine) in reversible cerebral ischemia produced in rats and Mongolian gerbils. Polyamine profiles did not change during ischemia, but did following recirculation. The most prominent changes were a dramatic postischemic increase in putrescine and a marked decrease in spermine in severely damaged regions. Within a given brain structure, the postischemic putrescine levels correlated closely with the density of ischemic cell injury and the time period of cerebral ischemia. Furthermore, putrescine was already considerably increased in the CA1-subfield of the hippocampus of gerbils after 8 h recirculation, i.e., at a time when the cells are still intact. The results indicate that putrescine may be viewed as an excellent biochemical correlate of ischemic cell injury. The postischemic changes in putrescine levels are discussed in relation to the known activities of this compound. PMID- 2907782 TI - [Beta-blockers in the treatment of glaucomatous and dry eyes]. PMID- 2907783 TI - [Report on the 6th European Congress on Radiology, Lisbon, May 31-June 6, 1987]. PMID- 2907785 TI - [Biocytin13]dynorphin A 1-13 amide: a potential probe for the kappa-opioid receptor. AB - A dynorphin A 1-13 amide (DYN) derivative biotinylated in position lysine 13 (B DYN) has been prepared by automated solid-phase peptide synthesis. The derivative retained its ability to bind to avidin, and B-DYN-avidin complex showed a dissociated half-life of 10 hr at 37 degrees C. Opioid receptor binding was measured in membrane preparations of rat brain (mu), NG-108-15 neuroblastoma glioma hybrid cells (delta), and guinea pig cerebellum (kappa). Biotinyl substitution of DYN either did not effect receptor binding (delta) or slightly reduced binding affinity (mu and kappa). Binding of B-DYN to the kappa receptor was very tight, with an IC50 value in the low picomolar range, while binding to mu and delta sites was over two orders of magnitude lower. Preassociation of B DYN with avidin resulted in a reduction of the affinities to the investigated opioid receptors by 100- to 1000-fold. However, the apparent affinity of B-DYN avidin for the kappa-opioid receptor is sufficient to suggest that B-DYN may be a useful tool for kappa-opioid receptor assay, localization, and purification. PMID- 2907784 TI - Effect of helenalin and bis(helenalinyl)malonate on nucleic acid and protein synthesis in human KB carcinoma cells. AB - Helenalin and bis(helenalinyl)malonate were shown to be cytotoxic against the growth of human KB carcinoma cells. DNA synthesis was inhibited significantly. This inhibition was afforded because of the drugs' effects on a number of enzyme activities. The inhibition of IMP dehydrogenase and ribonucleotide reductase complex activities correlated positively with the inhibition of DNA synthesis of the KB cells. DNA polymerase activity was inhibited by the drugs to a lesser degree. The deoxyribonucleotide pools were markedly reduced in the presence of the drug, which would be consistent with a blockage of the enzyme ribonucleotide reductase as well as suppression of DNA synthesis. XMP levels were also reduced, which is consistent with suppression of IMP dehydrogenase activity by the drugs. Ribonucleoside phosphate pools, particularly CDP and GDP, were elevated after drug treatment, which would be expected with a blockage at ribonucleotide reductase. Thus DNA alkylation is not the mechanism of action of the antineoplastic sesquiterpene lactones; rather, the cell-killing effect is related to DNA synthesis inhibition by the drug. PMID- 2907786 TI - Quantitative structure-activity study on human pharmacokinetic parameters of benzodiazepines using the graph theoretical approach. AB - The graph theoretical indices for a series of 13 benzodiazepines were calculated using a graph-path topological method. The total molecule, the ring fragments, and combinations of ring fragments were subjected to a quantitative structure activity analysis using eight pharmacokinetic parameters. The metabolic clearance and the blood-to-plasma concentration ratios were most highly correlated with the graph theoretical indices, with R values of 0.975 and 0.938, respectively. These correlations were found when the diazepine + benzo fragment and phenyl fragment were used to calculate the graph-path indices. Terminal disposition half-life was correlated with the benzo + diazepine fragment, with R = 0.969. Truncating the graph-path codes by eliminating cycles in the total molecule markedly improved the correlation coefficients. When compared to the graph-path indices for the total molecule, the correlation coefficients for the terminal disposition half life and metabolic clearance data rose from 0.721 to 0.935 and from 0.770 to 0.968, respectively, using the graph-path indices of the truncated molecule. Intrinsic clearance of unbound drug also was poorly correlated with the total molecule (r less than 0.7) but rose significantly using the graph-path indices of the truncated molecule (r = 0.971 and 0.975 for the well-stirred and parallel tube models, respectively). PMID- 2907787 TI - Searching for the endogenous benzodiazepine using the graph theoretical approach. AB - The graph theoretical indices of several compounds with reported benzodiazepine receptor binding affinities were calculated. Our results demonstrate a structural similarity among diazepam, triazolam, and the beta-carboline nucleus and a structural dissimilarity to the purines and nicotinamide. This result correlates with their respective binding affinities. Using the graph theoretical indices as structural descriptors of the benzodiazepines and the significant ligands of the beta-carbolines, a search for peptide sequences as potential ligands was explored. Single amino acids through pentapeptides with all possible amino acid substitutions and chemical modifications were calculated. The peptides generated were subjected to graph theoretical analysis, and their indices were compared to those of the benzodiazepines. Comparisons resulted in seven dipeptides and six tripeptides that are topologically similar to the benzodiazepines and beta carbolines. The dipeptides are histidine- or tryptophan-containing compounds with pyroglutamine, phenylalanine, and tyrosine residues in the second position. The tripeptides have two aromatic amino acid residues and a pyroglutamine or glycyl terminal residue. These structures are promising candidates because (1) they are structurally (topologically) similar to the benzodiazepines, represented by diazepam and triazolam, and to the beta-carbolines; and (2) they are sequences that may reasonably form a part of a larger peptide or that may be formed metabolically by proteolysis. PMID- 2907788 TI - Solubility and related physicochemical properties of narcotic analgesics. AB - The physicochemical properties of select opioid and anilinopiperidine narcotic analgesics were investigated. The solubilities of the narcotics in hexane and water and, for morphine, in other organic solvents were determined. Regular solution theory seems to be applicable to the solubility behavior of morphine in solvents that lack strong dipoles and hydrogen bonds. A best-fit solubility parameter of 13.2 (cal/cm3)1/2 for morphine was determined from its solubilities in London solvents and its ideal solubility. Calculation of morphine's solubility parameter from its hexane solubility alone and its melting properties gave a corresponding delta 2 value. These measured solubility parameters were appreciably larger than the solubility parameter estimated from molar attraction constants. Solubility parameters of hydromorphone, codeine, fentanyl, and sufentanil were also calculated from respective hexane solubilities, melting points, and heats of fusion and were 11.7, 10.9, 9.8, and 9.7 (cal/cm3)1/2. For these compounds, experimental solubility parameters agreed with solubility parameters estimated from molar attraction constants. Because meperidine, fentanyl, and sufentanil exhibit low levels of intracrystalline cohesion, as reflected in low melting points and relatively modest heats of fusion, theoretically projected ideal solubilities and actual solubilities in organic solvents measured for them were considerably higher than determined for morphine and its analogues. Consistent with the solubilities, the octanol-water partition coefficients of the two 4-anilinopiperidine analogues and of meperidine were several orders of magnitude larger than those of the opioids, evidencing the fact that meperidine, fentanyl, and sufentanil are substantially more lipophilic than the opioids. PMID- 2907789 TI - Effects of four brain-gut peptides injected into cerebroventricles on gastric motility of dogs. PMID- 2907790 TI - Central nervous system activity of terpenoids from marine sponge. AB - Some terpenoids extracted from marine sponge: triacetylated disidein, 2 tetraprenyl benzoquinol and 4 hydroxy-3-tetraprenylbenzoic acid 2-polyprenyl benzoquinols, avarol and furospongin-1 were tested by multidimensional Irwin screening and with some tests for analgesic and muscle relaxant activity. The three prenylhydroquinols derivatives and avarol show a good analgesic activity and low toxicity. PMID- 2907792 TI - Sex determination in mouse and man. PMID- 2907791 TI - Resveratrol activity on guinea pig isolated trachea from normal and albumin sensitized animals. AB - The relaxant effect of resveratrol on guinea pig isolated trachea (EC50 = 100 microM) was not due to interactions with histaminergic or cholinergic systems, but appeared to be influenced by beta-blockers, indomethacin and mepacrine. Antigen-induced contraction on sensitized trachea was partially antagonized by resveratrol. Resveratrol action may be partially related to arachidonic acid metabolism. PMID- 2907793 TI - Autosomal genes involved in mammalian primary sex determination. AB - Beginning with findings made during the late 1950s and early 1960s, evidence continues to accumulate in support of the hypothesis that the mammalian Y chromosome carries a gene that induces the undifferentiated foetal gonad in XY individuals to develop as a testis. Recently a DNA sequence has been isolated from the human Y chromosome that appears to be the hypothesized Y-linked testis determining gene, and advances have also been made toward identifying genes that interact with the Y-linked testis-determining (Tdy) gene to initiate testis formation. These loci have been identified in specific stocks of mice carrying the mutant Thp or TOrl allele at the T locus located on chromosome 17, and in crosses involving the transfer of a Y chromosome from two populations of Mus domesticus into the genomes of specific inbred strains of mice. The data in both cases support the hypothesis that there are several loci involved in testis determination and that abnormal interaction of these loci disrupts initiation of testis determination, resulting in development of ovarian tissue in XY individuals. PMID- 2907794 TI - Genetic control of sex determination in the germ line of Caenorhabditis elegans. AB - The nematode Caenorhabditis elegans normally exists as one of two sexes: self fertilizing hermaphrodite or male. Development as hermaphrodite or male requires the differentiation of each tissue in a sex-specific way. In this review, I discuss the genetic control of sex determination in a single tissue of C. elegans: the germ line. Sex determination in the germ line depends on the action of two types of genes:--those that act globally in all tissues to direct male or female development and those that act only in the germ line to specify either spermatogenesis or oogenesis. First, I consider a tissue-specific sex-determining gene, fog-1, which promotes spermatogenesis in the germ line. Second, I consider the regulation of the hermaphrodite pattern of germ-line gametogenesis where first sperm and then oocytes are produced. PMID- 2907795 TI - Molecular aspects of sex determination in mice: an alternative model for the origin of the Sxr region. AB - Using a combination of in situ mapping and DNA analysis with recombinant DNA probes specific for the Sxr region of the mouse Y chromosome, we show that both the gene(s) controlling primary sex determination and the expression of the male specific antigen H-Y (Tdy and Hya respectively) are located on the minute short arm of the mouse Y chromosome. We demonstrate that the H-Y- variant of Sxr (Sxr') arose by a partial deletion within the Sxr region and propose an alternative model for the generation of the original Sxr region. PMID- 2907796 TI - Mapping the human Y chromosome. AB - This paper reviews past and present trends in mapping the human Y chromosome. So far, mapping has essentially used a combination of cytogenetic and molecular analyses of Y-chromosomal anomalies and sex reversal syndromes. This deletion mapping culminated recently in the isolation of the putative sex-determining locus TDF. With the availability of new separation and cloning techniques suited for large size fragments (over 100 kilobases), the next step will consist rather in the establishment of a physical map of fragments of known physical sizes. This may allow the definition of several variants of the human Y chromosome differing by the order or location of DNA sequences along the molecule. PMID- 2907797 TI - Accidental X-Y recombination and the aetiology of XX males and true hermaphrodites. AB - Accidental recombination between the differential segments of the X and Y chromosomes in man occasionally allows transfer of Y-linked sequences to the X chromosome leading to testis differentiation in so-called XX males. Loss of the same sequences by X-Y interchange allows female differentiation in a small proportion of individuals with XY gonadal dysgenesis. A candidate gene responsible for primary sex determination has recently been cloned from within this part of the Y chromosome by Page and his colleagues. The observation that a homologue of this gene is present on the short arm of the X chromosome and is subject to X-inactivation, raises the intriguing possibility that sex determination in man is a quantitative trait. Males have two active doses of the gonad determining gene, and females have one dose. This hypothesis has been tested in a series of XX males, XY females and XX true hermaphrodites by using a genomic probe, CMPXY1, obtained by probing a Y-specific DNA library with synthetic oligonucleotides based on the predicted amino-acid sequence of the sex determining protein. The findings in most cases are consistent with the hypothesis of homologous gonad-determining genes, GDX and GDY, carried by the X and Y chromosomes respectively. It is postulated that in sporadic or familial XX true hermaphrodites one of the GDX loci escapes X-inactivation because of mutation or chromosomal rearrangement, resulting in mosaicism for testis and ovary-determining cell lines in somatic cells. Y-negative XX males belong to the same clinical spectrum as XX true hermaphrodites, and gonadal dysgenesis in some XY females may be due to sporadic or familial mutations of GDX. PMID- 2907798 TI - MIC2: a human pseudoautosomal gene. AB - MIC2 and XGR are the only known pseudoautosomal genes in man. MIC2 encodes the 12E7 antigen, a human cell-surface molecule of unknown function. XGR regulates, in cis, the expression of the XG and MIC2 genes. DNA probes derived from the MIC2 locus have been used in the construction of a meiotic map of the pseudoautosomal region and a long range restriction map into the X- and Y-specific chromosome domains. MIC2 is the most proximal marker in the pseudoautosomal region and recombination between the sex chromsomes only rarely includes the MIC2 locus. Our long-range restriction maps and chromosome walking experiments have localized the pseudoautosomal boundary within 40 kilobases adjacent to the 3' end of the MIC2 gene. The same maps have been used to predict the chromosomal location of TDF. PMID- 2907799 TI - Is ZFY the sex-determining gene on the human Y chromosome? AB - The sex-determining region of the human Y chromosome contains a gene, ZFY, that encodes a zinc-finger protein. ZFY may prove to be the testis-determining factor. There is a closely related gene, ZFX, on the human X chromosome. In most species of placental mammals, we detect two ZFY-related loci: one on the Y chromosome and one on the X chromosome. However, there are four ZFY-homologous loci in mouse: Zfy-1 and Zfy-2 map to the sex-determining region of the mouse Y chromosome, Zfx is on the mouse X chromosome, and a fourth locus is autosomal. PMID- 2907800 TI - Environmental regulation of sex determination in reptiles. AB - The various patterns of environmental sex determination in squamates, chelonians and crocodilians are described. High temperatures produce males in lizards and crocodiles but females in chelonians. Original experiments on the effects of incubation at 30 degrees C (100% females) or 33 degrees C (100% males) on development in Alligator mississippiensis are described. These include an investigation of the effect of exposing embryos briefly to a different incubation temperature on the sex ratio at hatching, and a study of the effects of 30 degrees C and 33 degrees C on growth and development of alligator embryos and gonads. A 7-day pulse of one temperature on the background of another was insufficient to alter the sex ratio dramatically. Incubation at 33 degrees C increased the rate of growth and development of alligator embryos. In particular, differentiation of the gonad at 33 degrees C was enhanced compared with 30 degrees C. A hypothesis is developed to explain the mechanism of temperature dependent sex determination (TSD) in crocodilians. The processes of primary sex differentiation are considered to involve exposure to a dose of some male determining factor during a specific quantum of developmental time during early incubation. The gene that encodes for the male-determining factor is considered to have an optimum temperature (33 degrees C). Any change in the temperature affects the expression of this gene and affects the dose or quantum embryos are exposed to. In these cases there is production of females by default. The phylogenetic implications of TSD for crocodilians, and reptiles in particular, are related to the life history of the animal from conception to sexual maturity. Those animals that develop under optimal conditions grow fastest and largest and become male. A general association between the size of an animal and its sex is proposed for several types of vertebrate. PMID- 2907801 TI - Somatic and germ-cell sex in mammals. AB - The phenotypic sex of an individual mammal is determined by the sex of its gonads, i.e. testes or ovaries. This in turn is determined by the presence or absence of a small region of the Y chromosome, located near the X-Y pairing region in man and on the short arm of the Y chromosome in the mouse. The testis determining region of the Y appears to exert its primary effect by directing the supporting-cell lineage of the gonad to differentiate as Sertoli cells, acting at least in part cell-autonomously. The phenotypic sex of a germ cell, i.e. whether it undergoes spermatogenesis or oogenesis, is determined at least in the mouse by whether or not it enters meiotic prophase before birth. This depends not on its own sex chromosome constitution, but on its cellular environment. A germ cell in or near normal testis cords (made up mainly of Sertoli cells) is inhibited from entering meiosis until after birth; one that escapes this inhibition will develop into an oocyte even if it is in a male animal and is itself XY in chromosome constitution. PMID- 2907802 TI - Sex determination in marsupials: evidence for a marsupial-eutherian dichotomy. AB - In this paper, we review briefly the current state of knowledge about sexual differentiation in eutherian mammals, and then describe the situation in detail in two marsupial species: the North American opossum and the tammar wallaby. The conventional explanation for the genesis of all male somatic sexual dimorphisms in mammals is that they are a consequence of the systemic action of testicular hormones. In the absence of testes, the embryo will develop a female phenotype. We present evidence for the tammar wallaby that calls into question the universal applicability of this hormonal theory of mammalian sexual differentiation. We have shown that extensive somatic sexual dimorphisms precede by many days the first morphological evidence of testicular formation, which does not occur until around the third day of pouch life. Male foetuses, and pouch young on the day of birth, already have a well-developed gubernaculum and processus vaginalis, paired scrotal anlagen, and a complete absence of mammary anlagen, whereas female foetuses and newborn pouch young have a poorly developed gubernaculum and processus vaginalis, no scrotal anlagen, and well-developed mammary anlagen. Because it seems unlikely that the male gonad could begin hormone secretion until after the Sertoli and Leydig cells are developed, our results strongly suggest that some sexually dimorphic somatic characteristics develop autonomously, depending on their genotype rather than the hormonal environment to which they are exposed. We have been able to confirm the hormonal independence of the scrotum, pouch and mammary gland by administering testosterone propionate daily by mouth to female pouch young from the day of birth; although the Wolffian duct was hyperstimulated, there was no sign of scrotal development, or pouch or mammary inhibition. When male pouch young were treated with oestradiol benzoate in a similar fashion, there was hyperstimulation of the Mullerian duct and inhibition of testicular migration and development, but no sign of scrotal inhibition or pouch or mammary development. Our results in the tammar wallaby are consistent with the earlier studies on the opossum, whose significance was not appreciated at the time. Further evidence in support of this hormonal independence comes from earlier studies of spontaneously occurring intersexes in several species of marsupial, including the opossum and the tammar wallaby. An XXY individual had intra-abdominal testes and complete masculinization of the male reproductive tract internally, but externally there was a pouch and mammary glands and no scrotum.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2907803 TI - Control mechanisms of testicular differentiation. AB - In this paper the importance of unknown factors responsible for the initial differentiation of a gonadal primordium is stressed. The hypothesis that in the absence of testis determining genes (TDG) the indifferent gonad is programmed to become an ovary is considered further. The TDG(s) are expressed only among cells already marked as gonadal cells, and they seem mainly to change the chronological sequence and intensity of expression of processes common to both sexes. The chronology of the normal events necessary for testicular differentiation and the fact that some of these events can be dissociated from one another under experimental conditions in vitro, suggest that many genes are involved in testicular differentiation and that the so-called testis-determining genes are probably regulatory genes. PMID- 2907804 TI - Role of mammalian Y chromosome in sex determination. AB - It has long been assumed that the mammalian Y chromosome either encodes, or controls the production of, a diffusible testis-determining molecule, exposure of the embryonic gonad to this molecule being all that is required to divert it along the testicular pathway. My recent finding that Sertoli cells in XX----XY chimeric mouse testes are exclusively XY has led me to propose a new model in which the Y acts cell-autonomously to bring about Sertoli-cell differentiation. I have suggested that all other aspects of foetal testicular development are triggered by the Sertoli cells without further Y-chromosome involvement. This model thus equates mammalian sex determination with Sertoli-cell determination. Examples of natural and experimentally induced sex reversal are discussed in the context of this model. PMID- 2907805 TI - H-Y antigen and sex determination. AB - The primary development of a male rather than a female gonad in mammals is determined by the presence of a Y chromosome. The other property unique to the Y chromosome is the occurrence of a cell-surface antigen (designated H-Y) which distinguishes male from female. Thus it was determined that male grafts were rejected by otherwise histocompatible females of the same inbred strain and later that H-Y-specific cytolytic T cells were produced by these grafted mice. When it was determined that females grafted with male skin produced antibody defining a serologically detectable male antigen (which may or may not be the same as H-Y), further immunogenetic analysis of this antigenic system became possible in terms of humoral and cellular factors. By using this assay it was demonstrated that the antigen was phylogenetically conserved and that it was expressed in the male mouse embryo as early as the 8-cell stage of development. The notion that H-Y was a single molecular species responsible for triggering the indifferent gonad to differentiate into the testis became a widely accepted hypothesis. In this report the H-Y antigenic system is traced historically from its original description to the role played in testis development. Data are presented which suggest that although H-Y is a male-specific factor and may play a role in male sex determination, it is unlikely that it is the primary inducer of testis differentiation. PMID- 2907806 TI - Aberrant chromosomal sex-determining mechanisms in mammals, with special reference to species with XY females. AB - Both mouse and man have the common XX/XY sex chromosome mechanism. The X chromosome is of original size (5-6% of female haploid set) and the Y is one of the smallest chromosomes of the complement. But there are species, belonging to a variety of orders, with composite sex chromosomes and multiple sex chromosome systems: XX/XY1Y2 and X1X1X2X2/X1X2Y. The original X or the Y, respectively, have been translocated on to an autosome. The sex chromosomes of these species segregate regularly at meiosis; two kinds of sperm and one kind of egg are produced and the sex ratio is the normal 1:1. Individuals with deviating sex chromosome constitutions (XXY, XYY, XO or XXX) have been found in at least 16 mammalian species other than man. The phenotypic manifestations of these deviating constitutions are briefly discussed. In the dog, pig, goat and mouse exceptional XX males and in the horse XY females attract attention. Certain rodents have complicated mechanisms for sex determination: Ellobius lutescens and Tokudaia osimensis have XO males and females. Both sexes of Microtus oregoni are gonosomic mosaics (male OY/XY, female XX/XO). The wood lemming, Myopus schisticolor, the collared lemming, Dirostonyx torquatus, and perhaps also one or two species of the genus Akodon have XX and XY females and XY males. The XX, X*X and X*Y females of Myopus and Dicrostonyx are discussed in some detail. The wood lemming has proved to be a favourable natural model for studies in sex determination, because a large variety of sex chromosome aneuploids are born relatively frequently. The dosage model for sex determination is not supported by the wood lemming data. For male development, genes on both the X and the Y chromosomes are necessary. PMID- 2907807 TI - Sex inversion as a model for the study of sex determination in vertebrates. AB - As a consequence of genetic sex determination, the indifferent gonadal blastema normally becomes either a testis or an ovary. This applies to mammals and to the majority of non-mammalian vertebrates. With the exception of placental mammals, however, partial or complete sex inversion can be induced in one sex by sexual steroid hormones of the opposite sex during a sensitive period of gonadogenesis. There is evidence that also during normal gonadogenesis in these species, in the XY/XX mechanism of sex determination testicular differentiation is induced by androgens, and in the ZZ/ZW mechanism, ovarian differentiation by oestrogens. In either case, the hormones may act via serological H-Y antigen as a morphogenetic factor. In contrast, in placental mammals including man, primary gonadal differentiation is independent of sexual steroid hormones, and factors directing differential gonadal development have not yet been conclusively identified. However, various mutations at the chromosome or gene level, resulting respectively in sex inversion or intersexuality, have provided clues as to some genes involved and their possible nature. In this context also, serological H-Y antigen is discussed as a possible factor acting on primordial gonadal cells and inducing differential growth or morphogenesis or both. The data available at present allow a tentative outline of the genetics of sex determination in placental mammals. PMID- 2907808 TI - The influences of cultural and racial factors upon therapeutic response of the schizophrenic patients. PMID- 2907809 TI - [Relations between therapeutic and hormonal response to neuroleptics of patients with paranoid schizophrenia. I. Secretion of thyrotropin and thyroid hormones]. PMID- 2907810 TI - [Relations between therapeutic and hormonal response to neuroleptics of patients with paranoid schizophrenia. II. Secretion of prolactin and gonadotropins]. PMID- 2907811 TI - [Relations between therapeutic and hormonal response to neuroleptics of patients with paranoid schizophrenia. III. Secretion of growth hormone (GH), adrenocorticotropic hormone (ACTH), cortisol (CORT) and insulin (INS)]. PMID- 2907812 TI - Noradrenaline-containing transplants in the adult spinal cord of mammals. PMID- 2907813 TI - Delayed stereotactic transplantation technique in non-human primates. PMID- 2907814 TI - Transplant improves hemiparkinsonian syndrome in nonhuman primate: intracerebral injection, rotometry, tyrosine hydroxylase immunohistochemistry. PMID- 2907815 TI - Implantation of genetically engineered cells to the brain. PMID- 2907816 TI - Physiology of graft-host interactions in the rat hippocampus. PMID- 2907817 TI - [Atrial natriuretic peptide receptors]. PMID- 2907818 TI - [Cardiac hypertrophy and its response to beta-adrenergic blockade]. PMID- 2907819 TI - [Effects of a new positive inotropic agent, OPC-8212 in patients with effort angina--comparison with beta-blocker, metoprolol]. PMID- 2907820 TI - [Assessment of chronotropic effect and arrhythmogenesis on beta 1-partial agonist (Xamoterol) in chronic heart failure]. PMID- 2907821 TI - [Arslan and Belloni acute nucleoreticular vestibular syndrome. Interpretation of changes in neuromediators]. PMID- 2907822 TI - [The current status and prospects of the use of beta blockers in aeronautical medicine]. PMID- 2907823 TI - Influence of salazosulphapyridine and 5-aminosalicylic acid on seminal qualities and male sex hormones. AB - Seminal abnormalities are a common side effect of salazosulphapyridine (SASP) treatment. We evaluated semen qualities and sex hormone concentrations in 11 patients with inflammatory bowel disease (IBD) during SASP treatment and 4 months after replacing SASP with an oral slow-release preparation of 5-aminosalicylic acid (5-ASA). Significant improvement in sperm count (p less than 0.01), morphology (p less than 0.02), and motility (p less than 0.02) could be observed during 5-ASA therapy, in comparison with SASP treatment. Three pregnancies occurred during the study period. The serum concentrations of gonadotrophins, prolactin, and sex hormone-binding globulin were normal in all patients and not significantly different in the two treatment periods. The mean total testosterone concentration decreased significantly (p less than 0.02) after 5-ASA substitution, together with serum albumin (p less than 0.005), although all values remained within normal limits. The apparent free testosterone concentration was not significantly different in the two treatment periods. It is concluded that a significant improvement in semen quality can be obtained in male patients with IBD after replacing SASP with 5-ASA. PMID- 2907824 TI - Effect of electric stimulation of the celiac vagus on gastric acid secretion and plasma concentrations of somatostatin and gastrin in the portal and gastroepiploic veins of dogs. AB - Electric stimulation (ES) of the celiac vagus during tetragastrin infusion reduced significantly the portal plasma concentration of somatostatin (SS) from 113 +/- 11.3 pg/ml to 87.8 +/- 5.8 pg/ml (P less than 0.05) in anesthetized dogs, in parallel with marked decrease of gastric acid secretion (59.9 +/- 7.1% of the prestimulatory value; P less than 0.01). A similar change in the portal plasma SS concentration was observed by ES of the celiac vagus on infusion of saline, with a concomitant significant increase in the portal plasma level of gastrin from a basal value of 65.9 +/- 7.0 pg/ml to a peak value of 129 +/- 29.9 pg/ml (P less than 0.05). However, no fluctuation of the plasma SS or gastrin level in the gastroepiploic vein was detected during or after ES of the celiac vagus. These findings indicate that gastric SS and gastrin are not of primary importance in the mechanism of inhibition of gastric acid secretion induced by ES of the celiac vagus in the dog. PMID- 2907825 TI - [The role of atriopeptin in the hypotensive effect of dynorphin]. PMID- 2907826 TI - [Effects of zinc and copper on the protection of somatostatin against islet B cell damage induced by streptozotocin]. PMID- 2907827 TI - Serum gamma-GTP levels by type and quantity of alcohol consumed--the 'whisky hypothesis' refuted. AB - Serum gamma-GTP measurements in 11,755 Japanese men were used to test the hypothesis that drinking whisky had little or no effect on the serum level of this enzyme. We found that regular drinking was associated with significantly increased mean levels and raised percentages of high values of gamma-GTP, irrespective of the type of alcohol consumed. Moreover, heavier and more frequent drinking were associated with proportionately greater increases in gamma-GTP levels. Our data therefore refute the hypothesis that whisky drinking is not accompanied by adverse changes in the level of serum gamma-GTP. PMID- 2907828 TI - New directions in asthma: some cause for concern. PMID- 2907829 TI - Continuous variation of agonist affinity constants. PMID- 2907830 TI - Validity of human brain autopsy samples for characterizing neurotransmitter function. PMID- 2907831 TI - The relationship of alpha-adrenoceptor reserve and agonist intrinsic efficacy to calcium utilization in the vasculature. PMID- 2907832 TI - Commentary on a review on the mechanism of ackee-induced vomiting sickness. PMID- 2907833 TI - [Current aspects of medical genetics in human medicine. Introduction]. PMID- 2907834 TI - [Structure and function of factor VIII and factor IX gene and molecular DNA diagnosis in hemophilia A and B]. PMID- 2907835 TI - [Genetic diagnosis in classical phenylketonuria]. PMID- 2907836 TI - [Molecular genetic aspects of diabetes mellitus]. PMID- 2907837 TI - [Clinical aspects, diagnosis and genetics of cystic fibrosis--a short review]. PMID- 2907839 TI - Drug resistant gene, resistant protein and their implication for therapy. PMID- 2907838 TI - Arylsulfatase A from human tissues contains an endo-beta-N-acetylglucosaminidase F-resistant oligosaccharide. AB - Homogeneous arylsulfatase A from human placenta, liver and urine contains two nonidentical subunits of 59 and 54 kDa. The two subunits are immunologically identical. The relative amount of low molecular weight subunits is only 20-30% of the total enzyme protein. Treatment of the enzyme under various conditions with endo-beta-N-acetylglucosaminidase F results in a decrease in the apparent molecular weight of both subunits by 1-2 kDa. a value that corresponds to the loss of a single N-linked oligosaccharide. However, as judged by carbohydrate staining, endo-beta-N-acetylglucosaminidase F does not remove all carbohydrate from the subunits or from glycopeptides of arylsulfatase A. In contrast, human prostatic acid phosphatase, a glycoprotein with a high content of mannose, hybrid and complex oligosaccharides is completely deglycosylated under identical experimental conditions. Several attempts to deglycosylate arylsulfatase A by chemical methods were unsuccessful due to poor recovery of the protein. From the present studies we conclude that arylsulfatase A contains an endo-beta-N acetylglucosaminidase F resistant, perhaps O-linked carbohydrate. PMID- 2907840 TI - Detection of drug resistance in human hematologic malignancy by monoclonal antibodies. PMID- 2907841 TI - Gene analysis in haemophilia A--restriction fragment length polymorphism and molecular defects in the factor VIII gene. PMID- 2907842 TI - Carrier detection of hemophilia A by DNA analysis. PMID- 2907843 TI - [Synthesis and the effect of new derivatives of perhydro-1,4,6-oxadiazocine on the central nervous system]. PMID- 2907844 TI - [Pharmacological studies of new derivatives of 7-amino-imidazo-[1,2-A] pyrimidine]. PMID- 2907845 TI - [Characteristics of newly isolated Bacillus sphaericus strains that are toxic to mosquitoes]. PMID- 2907847 TI - [Clinical syndromes caused by alteration of the hGH genes]. PMID- 2907846 TI - Characterization and purification of the F17 adhesin on the surface of bovine enteropathogenic and septicemic Escherichia coli. AB - The F17 antigen from bovine enterotoxigenic Escherichia coli strain (E coli 25KHO9), which adhered to calf intestinal villi, was isolated. An enterotoxin negative derivative (25KHO9st) was used for further studies. Using an immunogold labeling technique, the F17 antigen was characterized as a fimbrial protein. Pure fimbriae with a subunit molecular weight of 20,000 were obtained by homogenization and use of a sucrose gradient. The adhesion of E coli 25KHO9st was mediated by the F17 fimbriae, as both F17 antibodies and F17 protein blocked the adhesion of the strain 25KHO9st. The F17 fimbriae were serologically distinct from K88, K99, F41, and 987P fimbriae and did not agglutinate bovine, ovine, guinea pig, human, or chicken erythrocytes. Peptide fingerprint analysis revealed F17 and F(Y) adhesins to be homologous, if not identical. PMID- 2907848 TI - [Use of analgesics and antipyretics in pediatrics: introduction]. PMID- 2907849 TI - [Prognosis and treatment of glomerulonephritis of periarteritis nodosa. The role of plasma exchange]. AB - Fourteen patients with polyarteritis nodosa complicated by histologically confirmed glomerulopathies were included in a prospective multi-center study comparing corticotherapy (group 1, n = 8) with combined cyclophosphamide and steroids (group 2, n = 6). Plasma exchanges were associated on a routine basis. The two groups were comparable apart from initially more severe renal impairment in group 1 (p less than 0.05). Initial control of the disease was obtained in 11 patients (7 from group 1, 4 from group 2) including the patients with oligoanuria. Six patients recovered, 3 had recurrence requiring chronic hemodialysis and 5 patients died from group 1 (p less than 0.05). These preliminary findings suggest that plasma exchange can contribute to control of polyarteritis nodosa with renal complications. PMID- 2907850 TI - [Collection of blood stem cells and therapeutic applications]. AB - Peripheral blood stem cells were collected from 50 patients with different hematological malignancies. Leukaphereses (n = 263) were performed during the marrow regeneration phase following different types of chemotherapy. The mean number of CFU-GM collected per leukapheresis was 486 x 10(4), highest levels of CFU-GM being obtained in patients who received the most intensive chemotherapy and who had not been treated previously. Twenty-five patients underwent autologous blood stem cell transplantation. Hemopoietic recovery was complete and prompt in 24 patients. Only one patient had no megakaryocytic engraftment. These findings indicate that peripheral blood stem cells may be used for autologous transplantation in leukemic patients. PMID- 2907851 TI - The chromosome 19 linkage group LDLR, C3, LW, APOC2, LU, SE in man. AB - The data establish linkage in both sexes for LDLR:LW (zeta = 8.43 at theta = 0.00) and in the male for LDLR:LU (zeta = 3.31 at theta = 0.00) and for LW:APOC2 (zeta = 3.90 at theta = 0.00). They confirm LDLR:C3 and APOC2:LU linkage in both sexes, and LW:LU linkage in the male. The loci constitute two tightly linked gene clusters, LDLR, C3, LW and APOC2, LU, SE, distinguished by measurable linkage in female meioses within but not between clusters. Argument is supported for a 19p13.2-cen position for LW and a long arm position for LU and SE. PMID- 2907852 TI - Restriction fragment length polymorphisms of the complement component C4 loci on chromosome 6: studies with emphasis on the determination of gene number. AB - Restriction fragment length polymorphisms of the C4 region of human chromosome 6 have been studied in family material where the haplotypes are defined with regard to other genetic markers in this region. Employing one near full-length C4 probe and the combination of BglII and XbaI enzymes, five different C4 genes were characterized. Studies of the segregation of DNA patterns in families made possible the reliable determination of DNA C4 haplotype pattern including gene number. In the total material of 76 haplotypes, 13 different types with regard to number and/or DNA type of C4 gene(s) were encountered. Twelve of the haplotypes had one C4 gene only, 58 had two genes, while 6 had three C4 genes. This fits fairly well with the hypothesis that the one- and three-gene haplotypes have originated through unequal crossing-over between chromosomes carrying duplicated C4 genes. PMID- 2907853 TI - Klinefelter's syndrome: an analysis of the origin of the additional sex chromosome using molecular probes. AB - The results of our study of the origin of the additional X chromosome in 39 males with a 47,XXY chromosome constitution are reported. We used a total of 20 X linked RFLPs and successfully determined the origin of all 32 patients in whom DNA from both parents was available, and a further 3 in whom DNA was available from the patient and mother only. Males whose additional X chromosome was maternal in origin were further investigated using an X-linked centromere specific probe to determine the cell division at which the error occurred. Our results showed 53% of the non-disjunction to be attributable to pat mei I errors, 34% to mat mei I errors, 9% to mat mei II errors and 3% to a post-zygotic mitotic error. In the great majority of patients resulting from an error of maternal meiosis there was clear evidence of recombination involving the non-disjoined chromosomes, suggesting that absence of recombination is not an important aetiological factor in non-disjunction of the X chromosome in female meiosis. There was no alteration of parental age associated with the paternally derived 47,XXY males but a marked increase in maternal age among the maternally derived 47,XXY males, the increase being associated with mat mei I but not mat mei II errors. The proportion of paternally and maternally derived cases was similar among different ascertainment classes, suggesting that there is no dramatic effect of parental origin of the additional X chromosome on the phenotype of 47,XXY males. PMID- 2907854 TI - [Inhibitory effect of alpha-2 adrenoceptor antagonist (DG-5128) on intractable asthma--a double-blind, randomized, crossover study]. PMID- 2907855 TI - Effect of troxerutin and methionine on spin trapping of free oxy-radicals. AB - The cardioprotective agents troxerutin and methionine are radical scavengers and compete with the DMPO adduct formation of .OH generated by the Fenton reaction. The concentration of trapped .O2- generated by the xanthine oxidase/hypoxanthine reaction is lowered in the presence of troxerutin. The decay of DMPO-OH is decreased by troxerutin compared to the control. In the presence of methionine a carbon-centered radical is produced. The investigations support the opinion that the scavenging of oxygen derived free radicals is of importance for the cardioprotective action of these agents. PMID- 2907856 TI - Antivasodepressor action of antihistaminics determined ex vivo in the leg blood vessels of anaphylactic mice and rats. AB - In anaphylactic mice and rats vasodepression determined ex vivo in the isolated perfused hindlegs can partly be prevented by pretreatment of the animals with promethazine, cyproheptadine, astemizole, clemastine, cimetidine, and some of their combinations. Astemizole and clemastine were most active. However, there was no complete protection against vasodepression, indicating vasodepression mediators others than histamine to be involved in the development of vasodepression. PMID- 2907857 TI - Excellent results with clorazepate in recalcitrant childhood epilepsies. AB - Eleven children with severe incapacitating generalized seizures were treated with sodium valproate and clorazepate and responded with a marked decrease in seizure frequency. Three children received clorazepate alone, either because of valproate toxicity or because of parental concern over side effects. These children, 5 males and 6 females, ranged in age from 3 to 17 years. They manifested normal to severely retarded intelligence. Although valproate levels were in the therapeutic range, seizure control was inadequate. When clorazepate was added to valproate therapy a marked reduction in seizure frequency occurred within 24 hours and became optimal within 48 to 72 hours. Side effects were minimal with the exception of a nocturnal generalized tonic-clonic seizure in a single patient. Three children were withdrawn from therapy after a year because of recurrent seizures. One patient was restarted on therapy after 6 months and seizure control improved. Clorazepate may be a useful adjunct in the treatment of primary generalized seizures in children. PMID- 2907858 TI - Takayasu arteritis: a treatable cause of stroke in infancy. AB - Takayasu disease is an arteritis of unknown etiology involving the aorta and its major branches. Untreated, 75% of patients die within two years. A 6-month-old black female presented with a right focal seizure, a flaccid right hemiparesis, decreased pulses in the right arm, a large left frontoparietal hypodense area on computed tomography, and an elevated erythrocyte sedimentation rate. Cerebral angiography demonstrated irregular dilatation of both carotid arteries and narrowing of the left middle cerebral artery. Aneurysm of the right sinus of Valsalva, dilatation of the aortic root, narrowing of the origins of both carotid arteries, and beading of the descending aorta were demonstrated by cardiac angiography. The patient was treated with prednisone (2 mg/kg/day) and azathioprine (1 mg/kg/day). There was gradual return of the erythrocyte sedimentation rate to normal over the ensuing 3-10 months, resolution of the hemiparesis, and acquisition of normal developmental milestones. Digital subtraction angiography revealed improvement in the appearance of the descending aorta and of the common carotid arteries with the disappearance of the arterial wall irregularities. Early diagnosis and vigorous immunosuppression may improve outcome in this rare and often fatal vascular disease in childhood. PMID- 2907859 TI - King-Denborough syndrome: contracture testing and literature review. AB - The King-Denborough syndrome (KDS) is characterized by dysmorphic features, myopathy, and malignant hyperthermia (MH). Physiologic contracture testing for MH susceptibility has not been reported in KDS. A young boy with KDS underwent muscle biopsy evaluation at age 3 years that documented an abnormal contracture response to halothane, indicating MH susceptibility. Histopathology demonstrated small type II fibers associated with type I hypertrophy. Contracture testing of muscle obtained from the patient's mother was positive, while a sibling's test was negative. This case is the first to demonstrate susceptibility to MH with KDS by using physiologic contracture testing. The presence of positive MH results in both the patient and his mother suggest one of the following: (1) KDS may be part of the spectrum of autosomal dominantly inherited MH; (2) the locus for MH and for KDS may be linked closely and inherited concurrently, or; (3) the association of MH and KDS may be coincidental. PMID- 2907860 TI - [Aminoalkyl derivatives of benzotriazole and naphthotriazole]. PMID- 2907861 TI - The use of biofeedback in a behavioral program designed to teach an anxious child self-catheterization. AB - This paper presents a case study of a 7-year-old girl with a noncompliant bladder who was trained to self-catheterize using biofeedback and behavior therapy techniques. Initial attempts to train her to self-catheterize were unsuccessful owing to excessive amounts of fear, muscle tension, and refusal. After seven treatment sessions in which she was instructed in proper self-catheterization technique by a urology nurse clinician and coached in biofeedback-assisted relaxation by a clinical psychologist, the child successfully learned to self catheterize. EMG readings showed a decrease in quadriceps muscle tension levels across sessions. Eight additional sessions were held in order to train the child's parents in proper technique and coaching procedures. Through the use of portable biofeedback equipment during actual training sessions, the biofeedback served as a cue--first to the child and coach, and later to the child and parents -for when the child needed to stop and relax. This case illustrates the usefulness of biofeedback in a comprehensive behavioral program designed to teach self-catheterization to fearful children. PMID- 2907862 TI - Influence of stimulatory parameters on sinus node recovery time: an in vitro study. AB - The effects of pacing frequency, overdrive duration and stimulus amplitude on the sinus node recovery time (SNRT) were studied in the isolated right atrium of the rat. A positive relationship between pacing frequency and the SNRT was observed, whereas overdrive duration and stimulus amplitude did not affect SNRT. There was no significant interaction among the factors studied. The effect of frequency upon SNRT probably does not involve neurotransmitter release due to stimulation, since in vitro pretreatment with atropine plus propranolol does change the SNRT frequency relation. PMID- 2907863 TI - [Kinetic alterations of coagulation-anticoagulation and the fibrinolytic system in patients with epidemic hemorrhagic fever and their significance]. PMID- 2907864 TI - [Effects of ribavirin on coagulation-anticoagulation in patients with epidemic hemorrhagic fever]. PMID- 2907865 TI - The autonomic nervous system and related drugs in dental practice, Part II: Adrenergic agonists and antagonists. PMID- 2907866 TI - [The simultaneous administration of nifedipine and beta blockers]. PMID- 2907867 TI - Chemical mediators and treatment of pain in rheumatic disease. PMID- 2907868 TI - Circadian rhythm in gamma glutamyltranspeptidase and leucine aminopeptidase urinary activity in rats. AB - Urinary gamma glutamyltranspeptidase (GGT) and leucine aminopeptidase (LAP), renal tubular brush border enzymes, have been shown to be sensitive indicators of renal tubular functions. This study documents circadian rhythms in the urinary activity of GGT and LAP, statistically validated and quantified by the cosinor method, in 15 male Wistar rats standardized to a LD 12:12 illumination schedule (light from 0800 hr to 2000 hr) and fed ad libitum. The acrophase of the circadian rhythms in urinary GGT and LAP activity occurred at the end of the rest span of the animals: between 1730 and 1915 for GGT (depending on the mode of expression of the activity) and between 1700 and 1910 for LAP. Of striking resemblance in their timing, both these rhythms were also of large amplitude (about 50% of the mesor for urinary GGT activity and about 45% for LAP one). The circadian acrophases of urinary GGT and LAP activity led in timing the circadian rhythms in urine volume and creatinine excretion by about 13 hr. Such findings consistent with the circadian variations found by other investigators in GGT in kidney homogenates or in LAP in human urine thus reflect a periodicity in renal tubular function. The reasons for these circadian variations, still unknown at this time, are discussed. The influence recently demonstrated of the hormonal context on protein and enzyme synthesis at the tubule, and its phase relations to urinary enzyme excretion emphasize how much the circadian rhythm in urinary GGT and LAP activity is well included in the murine time structure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2907869 TI - [Effects of Ligusticum-carthamus injection on experimental cerebral edema]. PMID- 2907870 TI - Alanine:glyoxylate aminotransferase activities in liver of Suncus murinus (insectivora). AB - 1. The distribution of L-alanine:glyoxylate aminotransferase (AGT) activities were found in Suncus liver, 55% in particulate fraction and 45% in supernatant. 2. 65% of AGT activities in particulate were dependent on AGT isoenzyme 2 (AGT 2) having molecular weight 210,000, the remainder (35%) of AGT activities were dependent on AGT isoenzyme 1 (AGT 1) which have aminotransferase activity for serine. AGT activities in supernatant were dependent on AGT 1, AGT 2 and alanine:2-oxoglutarate aminotransferase (GPT), and their activity ratios were 10, 15 and 75%, respectively. 3. Km values for alanine were 0.52 mM; AGT 1, 3.3 mM; AGT 2, 0.88 mM; GPT measuring with AGT activity. AGT activity of GPT was inhibited by addition of glutamate and its Ki value was 1.8 mM. 4. Some other properties of AGT 1, AGT 2 and GPT are described. PMID- 2907871 TI - Comparative biochemistry of mammalian arylsulfatases A and B. AB - 1. Arylsulfatases A and B occurred as a major anionic and cationic isozyme, respectively, among eleven eutherian mammalian species. 2. Minor anionic arylsulfatase B isozymes were observed in rodents, dog, whale and pig, and were either monomeric (vole, Mr = 67 +/- 2 kDa), an apparent aggregate (dog, whale, pig; Mr = 192 +/- 10 kDa), or both (rat, mouse; monomeric Mr = 57 +/- 2 kDa; apparent dimeric Mr = 114 +/- 3 kDa). 3. Minor cationic arylsulfatase A isozymes were isolated from the deer, whale and pig. 4. Opossum arylsulfatases A and B were both anionic, had similar relative molecular weights, were not inhibited by silver, and were not precipitated by anti-murine arylsulfatase B nor anti-bovine arylsulfatase A IgG preparations. PMID- 2907872 TI - A polymorphic DNA marker on chromosome 10 linked to RBP3 on the MEN2A side. PMID- 2907873 TI - Glucocorticoid receptor maps to the distal long arm of chromosome 5. PMID- 2907874 TI - Genes for salivary proline-rich proteins and taste for phenylthiourea are not closely linked in humans. PMID- 2907875 TI - [A dynamic study of plasminogen, antithrombin III, fibrinogen and DIC in epidemic hemorrhagic fever]. PMID- 2907876 TI - [Study on neuro-endocrine type of gastric carcinoma]. AB - One hundred patients with gastric carcinoma resected surgically were studied by PAP immunoperoxidase and ultrastructural method. It was found that the tumor cells were positive for gastrin, serotonin, somatostatin as well as argyrophil particles in 19 patients. In these 19 patients, the quantity of endocrine tumor cells surpassed half of its total cancer cells in 4, leading to a separate entity of neuroendocrine gastric carcinoma. The authors hope to introduce this new subtype into the classification of gastric carcinoma. Among the 100 cases, 50 patients with undifferentiated carcinomas contained the NE cells in 16 (32%), the remains for high differentiated adenocarcinomas had the NE cells in 3 (6%) only. It was suggested that the appearance of NE tumor cells was closely correlated to differentiation of gastric carcinoma. This study theoretically demonstrated the heterogenicity of gastric carcinoma and supported the theory that different kinds of tumor cells (endocrine and nonendocrine) may have a common origin and are derived from the endoembryogenetic immature precursor cells. PMID- 2907877 TI - Absence of crystalluria and estimation of renal parameters after oral and intravenous ofloxacin as compared to placebo in healthy volunteers. AB - An open placebo-controlled study on eleven healthy male volunteers was carried out to investigate renal tolerance and the possibility of crystalluria after oral and intravenous administration of ofloxacin. Subjects received single doses of 200 and 400 mg ofloxacin orally, 200 mg ofloxacin intravenously, or placebo. Urine was collected in several fractions on each study day and the urine volume, excretion of ofloxacin, and excretion of creatinine, alanine aminopeptidase, N acetyl-beta-D-glucosaminidase, and gamma-glutamyltransferase were calculated in each fraction collected. Furthermore, the urine was investigated microscopically to determine whether ofloxacin crystals were present. Serum creatinine and creatinine clearance were also calculated. No relevant changes in creatinine clearance were observed and no drug crystals were found in the urine which indicates that renal tolerance was good. There were no differences in ofloxacin recovery after oral or intravenous administration, confirming that absolute bioavailability of the oral form is excellent. PMID- 2907878 TI - Tissue- and stage-specific control of homeotic and segmentation gene expression in Drosophila embryos by the polyhomeotic gene. AB - The distributions of the products of the homeotic genes Sex combs reduced (Scr) and Ultrabithorax (Ubx) and of the segmentation genes, fushi tarazu (ftz), even skipped (eve) and engrailed (en) have been monitored in polyhomeotic (ph) mutant embryos. None of the genes monitored show abnormal expression at the blastoderm stage in the absence of zygotic ph expression. Both Scr and Ubx are ectopically expressed in the epidermis of ph embryos, confirming the earlier proposal, based on genetic analysis, that ph+ acts as a negative regulator of Antennapedia (ANT C) and bithorax (BX-C) complex genes. At the shortened germ band stage, en is also ectopically expressed, mainly in the anterior region of each segment. In contrast to these effects in the epidermis, the expression of en, Ubx, Scr and ftz is largely or completely suppressed in the central nervous system, whereas eve becomes ectopically expressed in most neurones. PMID- 2907879 TI - Cell proliferation and early differentiation during embryonic development and metamorphosis of Hydractinia echinata. AB - The early embryonic development of Hydractinia lasts about 2.5 days until the developing planula larva acquires competence for metamorphosis. Most embryonic cells stop cycling on reaching the larval stage. In older larvae of Hydractinia, cells that are still proliferating occur exclusively in the endoderm in a typical distribution along the longitudinal axis. During metamorphosis, proliferation activity begins again. The number of S-phase cells has increased by the 9th hour after induction of metamorphosis. Proliferative activity starts in the middle gastric region and in basal parts of primary polyps. Tentacles and stolon tips are always free of replicating cells. PMID- 2907880 TI - Familial multiple endocrine neoplasia type I. PMID- 2907881 TI - Regulation of eukaryotic genes by cyclic-AMP. PMID- 2907882 TI - The F1-ATPase from Streptococcus cremoris: isolation, purification and partial characterization. AB - 1. The F1-ATPase from the plasma membrane of Streptococcus cremoris HA was released by low ionic shock wash and purified by gel filtration and ion exchange chromatography. 2. The specific activity of the purified F1-ATPase was 25.8 mumol Pi/mg protein/min. 3. Km for ATP was 0.80 mM, and Ki for ADP as a competetive inhibitor 0.40 mM. 4. The purified F1-ATPase consisted of five subunits, alpha, beta, gamma, delta and epsilon, with molecular masses of 47.0, 45.0, 29.5, 22.0 and 13.0 kDa, respectively. 5. The isoelectric point of the enzyme complex was found to be 4.4. PMID- 2907883 TI - Two spectrophotometric assays for D-amino acid oxidase: for the study of distribution patterns. AB - 1. Two simple, rapid and sensitive methods are described for measurement of D amino acid oxidase (DAO) activity using crude tissue extracts for the study of distribution patterns. 2. They detect products of oxidative deamination of D amino acids catalyzed by DAO, i.e. alpha-keto acids and H2O2 by measuring light absorbances at 445 and 500 nm, respectively. 3. Reliability of the methods was confirmed by quantitative detection of DAO added to the tissue extract, based on standard curves, time courses and values of Km and Ki, obtained using D-Ala as substrate. PMID- 2907884 TI - Isolation and characterization of chromosomal proteins from the mosquito Anopheles albimanus Weidemann. AB - 1. Nuclei were isolated from adult anopheline mosquitoes and fractionated into nucleolar chromatin, nucleoplasmic chromatin and ribonucleoprotein particles by sucrose density gradients. 2. Histones and nonhistone proteins were selectively dissociated from chromatin by treatment with sodium chloride, urea and guanidine HC1. 3. A special class of nonhistone proteins (tight proteins) were extracted from chromatin with Na4P2O7. 4. The electrophoretic properties of the histones, nonhistone proteins and ribonucleoprotein particles were examined by isoelectric focusing and SDS multiphase polyacrylamide gel electrophoresis. 5. By contrast to the histones, the nonhistone proteins displayed considerable heterogeneity. 6. Possible functional implications of the chromosomal proteins are discussed. PMID- 2907885 TI - Corrosion resistance of solder joints for removable partial dentures. PMID- 2907886 TI - [Evaluation of flow reserve in internal mammary artery in situ bypass]. AB - The internal mammary artery, when used as a conduit for coronary artery bypass, offers a better long-term patency and survival rate than the saphenous vein. However, concern exists that the flow through the internal mammary artery may be inadequate during periods of peak myocardial demand. This flow was investigated in 18 consecutive patients who were selected for coronary bypass of the left anterior descending artery using the internal mammary artery. All patients were evaluated post-operatively within 12 months by means of graded maximal stress test, cardiac catheterization and exercise thallium-201 scintigraphy. Significant improvement in work capacity, maximal rate-pressure product, effort angina and ECG abnormalities during exercise stress testing were observed following internal mammary artery myocardial revascularization. The patency rate for internal mammary artery grafts was 100% (vs 85% for vein grafts); during the followup period, occlusion of a saphenous vein bypass or development of a new stenosis in a native coronary artery was noted in five patients, and two patients were classified as having partial revascularization. Ischemia, demonstrated by perfusion deficits at peak stress which disappeared in the 3-hour delayed film, was documented in 7.4% (4/54) of the areas supplied by internal mammary artery grafts, compared to 31% (13/42) of the regions revascularized using saphenous vein conduits. Although this result was not statistically significant, a definite trend is suggested. We conclude that ischemia demonstrated by stress thallium scintigraphy in the post-operative period is uncommon when an internal mammary artery graft has been used. This suggests that adequate coronary flow exists at peak myocardial demand during exercise. PMID- 2907888 TI - Cryptorchidism. Proceedings of an ESPE symposium. 27th annual meeting of the European Society for Paediatric Endocrinology. Copenhagen, June 26-29, 1988. PMID- 2907887 TI - [Physiologic and hygienic characteristics of the work of video display terminal operators]. PMID- 2907889 TI - Surgical and hormonal therapy for cryptorchidism: an overview. AB - The treatment of the undescended testis still engenders controversy on both sides of the Atlantic. To date, there is still no consensus on how to treat a child with an undescended testis. Some physicians advocate surgical therapy of all children whose testes are not located at the bottom of the scrotum whereas others feel that hormonal therapy should be tried initially on all such boys. The following attempts to provide an objective assessment of each of these two therapeutic modalities, highlighting the current controversies. PMID- 2907890 TI - The embryology of testicular descent. AB - A description is given of the role of the gubernaculum testis in the migration of the testis from the intra-abdominal to the scrotal position. The morphological differences in the process between carnivores, ungulates and man on the one hand and rodents on the other are stressed. The importance of gubernacular outgrowth, gubernacular regression as well as the importance of intra-abdominal pressure is emphasized. The effects of some forms of abnormal gubernacular development on testicular descent are described. The hormonal factors possibly involved in the regulation of the gubernacular reaction are evaluated. LH-RH, gonadotropins, AMH and testosterone seem not to be responsible for gubernacular outgrowth but a low molecular weight fraction of a fetal testicular extract, called descendin, is stimulatory to gubernacular cells. There are indications that testosterone plays a role in the initiation of gubernacular regression. PMID- 2907891 TI - The epidemiology of cryptorchidism. John Radcliffe Hospital Cryptorchidism Research Group. AB - A total of 3,559 boys were examined for cryptorchidism over a 2-year period. At birth, 5.9% (210/3,534) had one or both testes undescended and at 3 months of age 1.61% (57/3,534) still had an undescended testis. These figures represent an increase in undescended testis of 40% at birth and 68% at 3 months when compared with figures collected in a similar study in the late 1950s. This increase in cryptorchidism still does not account for the increased number of orchiopexies being performed. Low birthweight was also found to be a risk factor for the presence of an undescended testis. PMID- 2907892 TI - Cryptorchidism and testicular neoplasia. PMID- 2907893 TI - Natural history of the maldescended testis. AB - In a series of 545 boys with undescended testis, 91 had bilateral spontaneous descent after the age of 10. Forty-five accepted to take part in an investigation of their fertility based on history, clinical examination, sperm analysis and estimation of serum FSH levels. In the majority, the volume of the testis was below normal and the sperm concentration was below the lower limit of the normal range. It is concluded that late spontaneous bilateral descent of the testis carries a serious risk of later impaired spermatogenesis. PMID- 2907894 TI - Endocrine and immunological findings in cryptorchid infants. AB - In cryptorchid infants, significantly decreased mean levels of plasma testosterone and luteinizing hormone (LH) were found between the ages of 30 and 120 days. The levels of testosterone and LH were significantly correlated. No significant difference was found between infants with bilateral or unilateral cryptorchidism. After 120 days there was no longer any significant difference between cryptorchid infants and controls. No significant change in plasma follicle-stimulating hormone (FSH) was found. These data suggest that subnormal secretion of LH could be the primary abnormality in a proportion of boys with so called common cryptorchidism. Our studies using LH-releasing hormone and human chorionic gonadotropin stimulation tests in older infants and children agree with the data obtained by measurement of basal plasma hormone levels during the first months of life. Anti-gonadotroph antibodies were found in the sera of approximately 50% of the cryptorchid children and infants studied, using an immunofluorescence technique. A study of 17 mothers and their infants gave concordant results in 16 pairs, 9 with and 7 without antibodies. This lead us to speculate on the possible role of maternal autoantibodies as a cause of partial gonadotrophin deficiency in the perinatal period and thus of testicular maldescent. As cryptorchidism is a syndrome, these findings do not mean that a similar mechanism is operative in all cases. However, these data do suggest that alternatives to the classical anatomical view of the descent and nondescent of the testes should be considered. PMID- 2907895 TI - Hormonal treatment of cryptorchidism. AB - Hormonal treatment of cryptorchidism with a gonadotropic substance from pregnancy urine or with an anterior-pituitary-like substance dates from the early 1930s. Success rates varied from 25 to 100%. Subsequently, human chorionic gonadotropin (hCG) administered intramuscularly came into use. The success rates of several large studies have varied from 25 to 55%. Widely divergent results have, likewise, been reported following the intranasal administration of luteinizing hormone-releasing hormone (LHRH), the efficacy of which has been investigated in many studies, including placebo-controlled trials. Combined LHRH and hCG treatment schedules have been recently assessed, with equally divergent success rates. The most important factor influencing the rate of success is the testicular position before treatment: the lower the position of the testis before treatment the better the result. The experience with LHRH nasal spray treatment for cryptorchidism in 252 prepubertal boys is presented in this study, including several years follow-up, and the results compared with data reported in the literature. PMID- 2907896 TI - Treatment of cryptorchidism with human chorionic gonadotropin or gonadotropin releasing hormone. A double-blind controlled study of 243 boys. AB - We have conducted a modified double-blind study on the effect of human chorionic gonadotropin (hCG), gonadotropin releasing hormone (GnRH) and placebo on bilateral and unilateral maldescended testes. One hundred and fifty-five boys with bilateral and 88 boys with unilateral cryptorchidism fulfilled the inclusion criteria and completed the treatment protocol. The boys were between 1 and 13 years of age. hCG was administered as intramuscular injections twice weekly for 3 weeks. GnRH and placebo were given intranasally. hCG was superior to GnRH and placebo in the treatment of bilateral maldescended testes (p = 0.0009). Both testes descended in 25% of the boys following treatment with hCG, and improvement in the position of the testes was obtained in a further 25% of the cases. hCG administration resulted in complete testicular descent in 14% of boys with unilateral cryptorchidism compared with 3 and 0% after placebo and GnRH, respectively (p = 0.07). The testis had moved to a more distal position in 46% of the boys treated with hCG. There was no significant difference between the treatment groups with regard to age or initial position of the testes. We conclude that a success rate of 25% justifies the use of hCG in the treatment of maldescended testes, whereas the study did not support a general use of GnRH administered intranasally. PMID- 2907897 TI - Three injections of human chorionic gonadotropin are as effective as ten injections in the treatment of cryptorchidism. AB - Two schedules of human chorionic gonadotropin (hCG) administration were compared in a study of 332 boys (473 testes) aged 1-13 years with cryptorchidism. One group of patients received 10 hCG injections according to the International Health Foundation (IHF) schedule while the other group received 3 hCG injections at intervals of 7-10 days (1-3 years = 3 x 1,000 IU; 3-6 years = 3 x 1,500 IU; 6 10 years = 3 x 3,000 IU; 10-13 years = 3 x 5,000 IU hCG). Results from both schedules were comparable during the first and also during a second treatment period at the age of 1-3 and 3-6 years; between 6 and 13 years of age the IHF schedule was more successful. PMID- 2907898 TI - Undescended testis: comparison of two protocols of treatment with human chorionic gonadotropin. Effect on testicular descent and hormonal response. AB - A randomized study of two protocols of human chorionic gonadotropin (hCG) treatment was performed in 183 prepubertal boys between 7 months and 12 years of age: protocol I, in which the boys were given 7 injections of 1,500 IU every other day, and protocol II consisting of 4 injections of 100 IU/kg at 4- to 5-day intervals. In both protocols, by the end of the test, testosterone had risen significantly to values within the normal adult male range. However, the amplitude of the rise was slightly but significantly lower using protocol II (4.08 +/- 2.07 ng/ml) than protocol I (5.16 +/- 2.73 ng/ml). It would thus appear that repetition of the hCG injection at intervals of less than 4 days is unnecessary, and that a total stimulation period of 2-3 weeks is sufficient. Although not correlated with testosterone levels, the success rates for treatment were similar in both protocols and comparable to rates reported in the literature. PMID- 2907899 TI - Treatment with human chorionic gonadotropin induces inflammation-like changes in the testicular microcirculation in adult unilaterally cryptorchid rats. AB - Treatment of adult unilaterally cryptorchid rats results in an increased vascular permeability in the testes. This response is however more pronounced in abdominal than in scrotal testes. PMID- 2907900 TI - Long-term effect of a luteinizing-hormone-releasing hormone analogue (buserelin) on cryptorchid testes (extended summary). PMID- 2907901 TI - [Unusual reactions induced by contact with the Pelagia noctiluca medusa. Presentation of 3 cases]. PMID- 2907902 TI - Action of cholesterol on virulence related biochemical functions of Entamoeba histolytica. PMID- 2907903 TI - Changes in brain biogenic amines under influence of an indigenous drug, geriforte, following immobilization stress. PMID- 2907904 TI - Heavy drinking and accidents--a prospective study among men of working age. AB - The injuries of 438 consecutive men of working age (20-64 years) were investigated. These patients were admitted to the Department of Orthopaedics and Traumatology of the Helsinki University Central Hospital. The MAST interview was used as the criterion for heavy drinking. Of the whole series 27.4 per cent met the heavy drinking criterion and in 36.4 per cent alcohol intoxication (AI) was present on admission. AI was more common in heavy drinkers (62 per cent) compared with the controls (23 per cent) (chi 2 test, P less than 0.001). S-GGT was elevated in 34 per cent of the heavy drinkers. Elevated levels of S-GGT among heavy drinkers also correlated with postoperative complications. The hospital stay of the heavy drinkers compared with the controls was statistically significantly longer (10.7 days versus 7.3 days). Although the proportion of alcohol intoxication among heavy drinkers was high, of the heavy drinkers almost 40 per cent were sober on admission. Interviews, such as MAST are recommended for use routinely with injured patients to assess alcohol abuse 'through accidents'. PMID- 2907905 TI - Platelet alpha 2-adrenoceptor binding in migraine. PMID- 2907906 TI - The aching head. Intracranial suppuration due to head and neck infections. AB - Many infections of the head and neck may progress to cause more serious suppurative complications that involve the brain and its associated structures. Because many, if not all, of these infectious diseases present as headache, it would be appropriate to discuss all these clinical entities, but because of space limitations, this article focuses on brain abscess, subdural empyema, and cranial epidural abscess. These three pyogenic infections are reviewed in relation to their causal relationship to common and important pericranial infections. PMID- 2907907 TI - [Role of endogenous norepinephrine and effects of alpha- and beta-blockers in experimental spinal cord compression injury]. AB - The changes in spinal cord micro-circulation were investigated after administering alpha- and beta-blockers to rabbits with acute spinal cord injury. Immediately after the 8th thoracic spinal cord was injured by applying pressure with a weight (50 g) for 1 minute, an alpha or beta-blocker was injected into the subarachnoid space of the injured region of the spinal cord. Spinal cord edema, blood flow, vascular permeability, and the mean arterial pressure were compared between the groups treated with each agent and the control group. One hour after the injury, the water content of the spinal cord was significantly lower in the phenoxybenzamine-treated group than in the control group. After 6 hours, however, no significant difference was observed between these two groups. The spinal cord blood flow was higher in the phenoxybenzamine-treated group than in the control group until 6 hours after the injury. These results suggest involvement of norepinephrine in the formation of edema at the early stage of spinal cord injury. PMID- 2907908 TI - [Recent progress in diagnosis and treatment of digestive diseases. I. Chronic gastritis and peptic ulcer. 1. Chronic gastritis and uncertain complaint of the abdomen]. PMID- 2907909 TI - [Recent progress in diagnosis and treatment of digestive diseases. I. Chronic gastritis and peptic ulcer. 3. Drug treatment of peptic ulcer disease-including maintenance therapy in the prevention of recurrence]. PMID- 2907910 TI - [Recent progress in diagnosis and treatment of digestive diseases. III. Inflammatory bowel diseases. 7. Medical treatment of ulcerative colitis and Crohn's disease]. PMID- 2907911 TI - Comparison of the efficacy of four antihistamines in chronic urticaria. PMID- 2907912 TI - Chronic treatment with dopamine receptor antagonists: behavioral and pharmacologic effects on D1 and D2 dopamine receptors. AB - Rats were treated for 21 d with the selective D1 dopamine receptor antagonist SCH23390, the selective D2 dopamine receptor antagonist spiperone, the nonselective dopamine receptor antagonist cis-flupentixol, or a combination of SCH23390 and spiperone. In addition, a group of rats received L-prolyl-L-leucyl glycinamide (PLG) for 5 d after the 21 d chronic spiperone treatment. Chronic treatment with SCH23390 resulted in a significant increase in D1 dopamine receptor density with no change in the D2 dopamine receptor density. Conversely, spiperone treatment resulted in a significant increase in D2 dopamine receptors and no change in D1 dopamine receptor density. PLG treatment had no effect. SCH23390 plus spiperone treatment resulted in a significant increase in both D1 and D2 dopamine receptor densities. However, although in vitro cis-flupentixol has an equal affinity for D1 and D2 dopamine receptors, only the D2 dopamine receptor density increased after chronic treatment with cis-flupentixol. In vivo treatment with the protein-modifying reagent N-ethoxycarbonyl-2-ethoxy-1,2 dihydroquinoline (EEDQ), which irreversibly inactivates D1 and D2 dopamine receptors, was used to investigate the paradoxical, selective D2 dopamine receptor up-regulation induced by cis-flupentixol treatment. In vivo treatment with cis-flupentixol before EEDQ administration prevented the D1 and D2 dopamine receptor reductions induced by EEDQ. However, cis-flupentixol protected, in a dose-dependent manner, a greater percentage of D2 dopamine receptors than of D1 dopamine receptors from EEDQ-induced modification. These data indicate that, in vivo, cis-flupentixol preferentially interacts with D2 dopamine receptors and could explain why only D2 dopamine receptors were up-regulated following chronic treatment with cis-flupentixol. Rats were tested for their cataleptic response to the administered drug over the course of the chronic drug treatment. Catalepsy scores of rats receiving spiperone decreased over the course of treatment, with a significant reduction in catalepsy occurring by treatment day 5. The profound catalepsy observed in rats receiving SCH23390 did not change over the 21 d of treatment. Rats receiving cis-flupentixol demonstrated tolerance to its cataleptogenic effects, with a significant reduction in catalepsy observed by treatment day 7. During the 3 week treatment, the time between drug injection and a full cataleptic response to cis-flupentixol increased from 20 to 60 min, suggesting a tolerance to the D2, but not D1, dopamine receptor antagonism by cis flupentixol.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2907913 TI - Neuropeptide Y modulates neurotransmitter release and Ca2+ currents in rat sensory neurons. AB - Using 125I-labeled neuropeptide Y (NPY) and peptide YY (PYY), we demonstrated the existence of specific receptors for these peptides on rat dorsal root ganglion (DRG) cells grown in primary culture. Scatchard analysis of membrane homogenates indicated that the peptides bound to 2 populations of sites, with approximate affinities of 0.08 and 6.5 nM. Only low levels of binding were detected on sympathetic neurons cultured from the same animals or on a variety of neuronal clonal cell lines. The binding of 125I-NPY and 125I-PYY to DRG cell membranes was considerably reduced by the nonhydrolyzable analog of GTP, Gpp(NH)p. The major effect of Gpp(NH)p was to reduce the number of lower-affinity NPY binding sites without altering the number of high-affinity binding sites. NPY potently inhibited Ca2+ currents recorded under voltage clamp in rat DRG cells. Both the transient and sustained portions of the Ca2+ current were inhibited. The inhibitory effects of NPY were completely blocked following treatment of the cells with pertussis toxin. Depolarization elicited a large influx of Ca2+ into DRG neurons as assessed using fura-2-based microspectrofluorimetry. This influx of Ca2+ could be partially inhibited by NPY. Furthermore, NPY effectively inhibited the depolarization-induced release of substance P from DRG cells in vitro. Thus, NPY may be an important regulator of sensory neuron function in vivo. PMID- 2907914 TI - [Phonocardiographic and two-dimensional and pulsed Doppler echocardiographic studies of Still's murmurs]. AB - The prevalence of Still's murmur was examined by phonocardiographic study, and the clinical significance of this murmur was investigated using pharmacodynamic phonocardiography and echocardiography. Still's murmur was present in 224 of 9,478 cases (2.4%) in school children. Its prevalence was 143 in 4,524 (3.2%) in elementary school children and this was significantly greater than that in middle school youngsters who numbered 81 among 4,954 (1.6%) (p less than 0.001). There were neither abnormal findings on two-dimensional echocardiography, nor pathological regurgitant signals on pulsed Doppler examination. After the inhalation of amyl nitrite, Still's murmur was accentuated by 5.3 +/- 3.0 dB, and was louder in the expiratory than in the inspiratory phase by 4.7 +/- 3.5 dB. PMID- 2907915 TI - [Role of cardiac nerves in determination and modulation of blood pressure oscillation pattern]. AB - Effects of autonomic innervation of the heart for blood pressure oscillation (BPO) caused by a side pressure exertion procedure in rabbits were studied by intravenous administrations of atropine or beta-blockers (metoprolol and propranolol). When relatively large doses of these drugs were injected the oscillation disappeared. Atropine injection caused three types of effects on BPO: mostly abolition, diminution and sometimes augmentation. In the diminished cases, the oscillation waves were subjected to a successive decrease in the height and the gradient of ascending limbs. And the extent of bradycardia on the descending limb was less than that of the control. In the augmented cases which accounted for one fifth of all the results, the injection enhanced the BPO in wave height and gradient. Meanwhile, the administration of beta-blockers resulted in disappearance or a decrease in wave height and gradient of the ascending limbs of waves. From these, it is suggested that cardiac sympathetic and vagal discharges accelerate blood pressure rise of the ascending limb, and vagal discharges contribute to active descent of each wave. It is suggested that the BPO is influenced not only by the periodic change of the total peripheral resistance but also by the concomitant changes in tones of cardiac nerves. PMID- 2907916 TI - Differential acute and chronic response of protein kinase C in cultured neonatal rat heart myocytes to alpha 1-adrenergic and phorbol ester stimulation. AB - Both alpha 1-adrenergic agonists (e.g. norepinephrine, NE*) and tumor-promoting phorbol esters (e.g. phorbol myristate acetate, PMA) are known to activate protein kinase C (PKC) (Abdel-Latif, 1986, Niedel and Blackshear, 1986). However, alpha 1 agonists and PMA produce very different effects on cardiac function (see Simpson, 1985; Benfey, 1987; Meidell et al., 1986; Leatherman et al., 1987; Yuan et al., 1987; for examples). PKC activation in heart cells has been studied only for PMA treated perfused heart (Yuan et al., 1987). Therefore, acute activation and chronic regulation of PKC by NE and PMA were compared in cultured neonatal rat heart myocytes. NE acutely and transiently activated PKC, as measured by translocation of PKC activity to the cell particulate fraction (Niedel and Blackshear, 1986). Particulate PKC activity peaked at 23% of total after NE for 30 s, as compared with 8% for control (P less than 0.001). By contrast, acute PKC activation by PMA was more pronounced and persistent, with particulate PKC activity 62% of total at 5 min (P less than 0.001). Calcium/lipid-independent kinase activity increased acutely with PMA, but not with NE. Chronic treatment with NE (24 to 48 h) increased total per cell PKC activity and 3H-phorbol dibutyrate (PDB) binding sites, an index of the number of PKC molecules (Niedel and Blackshear, 1986), by 30 to 60% over control (all P less than 0.05 to 0.01). In contrast with NE, chronic treatment with PMA down-regulated PKC, reducing total per cell PKC activity and 3H-PDB binding sites to 3% and 12% of control, respectively (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2907917 TI - [Purification and characterization of Vibrio parahaemolyticus pili isolated from a patient with diarrhea: comparative studies with Vibrio cholerae O1 pili]. PMID- 2907918 TI - [Carbohydrate antigens in embryo and their clinical application]. PMID- 2907919 TI - [Measurement of thyroid growth stimulating and inhibiting autoantibodies: examination using FRTL-5 cells]. PMID- 2907920 TI - [Changes in neurotransmitters in Alzheimer-type dementia]. PMID- 2907921 TI - Tetrodotoxin-unaffected depolarization of frog muscles induced by the venom of jellyfish (Genus aurelia). AB - In the isolated frog muscle, the proteinaceous venom extracted from jellyfish (genus Aurelia) produced 1) a complete and irreversible block of indirectly and directly elicited muscle twitch and 2) an irreversible depolarization of the muscle membrane. This venom-induced depolarization was effectively reversed or prevented by the substitution of choline for sodium in Ringer solution, but not by the introduction of tetrodotoxin (TTX), a sodium channel blocker. The mechanism of muscle membrane depolarization appears to involve probably an increase in membrane permeability to sodium ion as shown by the decrease in membrane resistance. These results suggest that the venom forms a pore which has sodium selectivity or activates a TTX-insensitive sodium channel which is different from the known sodium channel. PMID- 2907922 TI - [Analysis of localized blood velocity in the grafts during coronary revascularization surgery--comparison of the saphenous vein with internal mammary artery]. PMID- 2907923 TI - Decrease in prolactin receptor affinity in the rat mammary tumor model after treatment with analogs of somatostatin and LH-RH. PMID- 2907924 TI - [Persistent infection caused by hemorrhagic fever with renal syndrome virus in bank voles (Clethrionomys glareolus)--the natural host of the virus]. PMID- 2907925 TI - [Determination of specific immune complexes and dynamics of their circulation in patients with hemorrhagic fever with renal syndrome]. PMID- 2907926 TI - [Double control of pili formation in Yersinia pestis]. PMID- 2907927 TI - [Transmembrane currents in Xenopus oocytes after an injection of brain mRNA]. AB - The possibility of the translation of mRNA isolated from bovine brain and injected into Xenopus oocytes has been shown. It is found that mRNA injection induced the appearance of voltage-operated TTX-sensitive sodium and calcium currents, GABA receptors in oocytes membrane. PMID- 2907928 TI - Outcome of treatment with haloperidol decanoate in a patient with schizophrenia, chronic undifferentiated type, and end stage renal disease. PMID- 2907929 TI - [Use of a chlordemethyldiazepam-fentanyl combination in invasive neuroradiologic examinations]. PMID- 2907930 TI - [Comparative study of the action of dalargin and obsidan on the course of acute myocardial infarction in an experiment]. PMID- 2907932 TI - The institutionalized mental health patient's right to refuse psychotropic medication. PMID- 2907933 TI - Maintenance medication for chronic schizophrenics: risk/benefit assessment. AB - The following are key factors to consider in assessing a patient for long-term neuroleptics: 1. Who--accurate diagnosis of schizophrenia is of primary concern. There are no good prognostic indicators other than a history of repeated relapses and positive responses to neuroleptics. 2. When and for how long--should always be considered for the patient who has had more than two acute episodes. The first year post-acute episode back in the community is extremely critical. Consider maintaining patient on tapering dosage of medication for at least four to five years. 3. What benefits--symptoms of acute psychosis respond, those of chronic defect state do not. Medication also can act as buffer against stress. 4. Dosages -standard range is the equivalent of 300-800 mg. of Thorazine for most patients. Dose range for depot administration of Prolixin decanoate is 25-62.5 mg. 2-4 week intervals. Differences within this range may not be important. Data about very low doses (one-tenth standard dose) and megadoses (4-5 times standard dose) are inconsistent. 5. Risks--extrapyramidal symptoms, tardive dyskinesia, and akinetic depression are the most prevalent risks. Extrapyramidal symptoms can often be controlled effectively with dosage reduction. However, anticholinergic drugs are the treatment of choice during acute phases, and for the first 3-5 months post acute phase. Tardive dyskinesia rarely occurs after a few weeks or months, but occurs most commonly beginning after two years of drug treatment. The usual form is persistent, but transient forms also occur. The earliest signs are reversible in some patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2907931 TI - [Acute myopathy caused by psychotropic agents. Report of 2 cases]. PMID- 2907934 TI - [Selected aspects of aerosol therapy]. PMID- 2907935 TI - Collagenous colitis: response to treatment. PMID- 2907936 TI - Somatostatin in neuropsychiatric disorders. AB - 1. Somatostatin is a peptide that is widely and discretely distributed throughout the central nervous system. 2. Its relevance to neuropsychiatric disorders is suggested both by the existence of disease-related alterations in somatostatin content in brain and cerebrospinal fluid as well as by the manifold neuroregulatory capabilities of somatostatin and related peptides. 3. This article will summarize the central nervous system effects of somatostatin, identify those neuropsychiatric disorders that are characterized by changes in somatostatin, and review the evidence for and potential significance of decreases in cerebrospinal fluid somatostatin in depression. PMID- 2907938 TI - [Biosynthesis, processing and release of gamma-glutamyltranspeptidase]. PMID- 2907937 TI - [Gamma-glutamyl cycle]. PMID- 2907939 TI - [Cancer-associated-changes in gamma-glutamyl transpeptidase]. PMID- 2907940 TI - [Induction of gamma-glutamyltranspeptidase in animal tissues]. PMID- 2907941 TI - [Gamma-glutamyltranspeptidase of bacteria]. PMID- 2907942 TI - [Genes for enzymes of glutathione biosynthesis]. PMID- 2907943 TI - [Long-term effect of xamoterol "Corwin", beta 1 partial agonist, on hemodynamics and treadmill exercise in patients with previous myocardial infarction]. PMID- 2907944 TI - [Current trends and prospects in pharmacotherapy with anxiolytics]. PMID- 2907945 TI - [Culicidae as vectors of pathogenic agents]. PMID- 2907946 TI - [Neurotoxic effects of glutamic acid]. PMID- 2907947 TI - [Role of the central nervous system in the pathogenesis of stress ulcer]. PMID- 2907948 TI - [The influence of blocking habenulae or medial forebrain bundles on the analgesic effect elicited by administration L-glutamic acid into the septa]. PMID- 2907949 TI - [Basic and clinical study on combined immunomodulator therapy in rheumatoid arthritis]. PMID- 2907950 TI - [Evaluation of salazosulfapyridine enteric-coated capsules in therapy of rheumatoid arthritis]. PMID- 2907951 TI - [The uterus relaxing betamimetics]. PMID- 2907952 TI - Transmitter release from brain slices elicited by single pulses: a powerful method to study presynaptic mechanisms. PMID- 2907953 TI - Caffeine interactions with multiple neurotransmitter systems. PMID- 2907954 TI - Dopaminergic drugs in the cationic form interact with D2 dopamine receptors. PMID- 2907955 TI - [Studies on acetyl-CoA synthetase of Candida tropicalis producing dicarboxylic acids from alkanes]. PMID- 2907956 TI - [Pharmacogenetic studies on drug dependence]. AB - Great strides have been made in recent years in researchers' knowledge and understanding of genetic factors contributing to drug dependence. In this paper, pharmacogenetic studies on drug dependence are reviewed. The strain which has been maintained by inbreeding for 20 or more generations may be regarded as being genetically uniform. Significant differences between inbred strains on a particular response represent presumptive evidence of genetic determination of that response. Selective breeding is another genetic approach and refers to the systematic intermating of selected individuals for the purpose of changing the genetic and phenotypic characteristics of a population. This usually takes the form of changing the population mean in two opposite directions, such as AA and ANA, LS and SS, etc. Using inbred animal strains and selective lines, a variety of evidence indicates that acute effects of, tolerance to, and dependence on abusable drugs are controlled by genetic factors. Many investigations have compared the effects of abusable drugs with various biochemical traits. The use of certain genetically defined animal models can be very helpful in studies of drugs of abuse. The choice of model will be influenced by the aims of the study. PMID- 2907957 TI - [Effects of bifemelane on central dopaminergic and cholinergic systems in rats]. AB - The study served to examine the effects of bifemelane on central dopaminergic cholinergic neuronal mechanisms in rats. Bifemelane (5-20 mg/kg) evoked yawning responses, the frequency being low. Bifemelane (10 mg/kg) as well as bromocriptine (2.5 mg/kg) potentiated physostigmine (0.2 mg/kg)-, bromocriptine (2.5 mg/kg)- or apomorphine (0.1 and 0.5 mg/kg)-induced yawning but completely inhibited pilocarpine-induced yawning. Pretreatment with sulpiride (20 mg/kg) and a low dose of haloperidol (0.02 mg/kg) reversed the stimulatory effect of bifemelane on physostigmine-induced yawning and the inhibitory effect of the drug on pilocarpine-induced yawning, whereas atropine (5 mg/kg) diminished these yawning responses. SK&38393 (2.0 mg/kg), a dopamine D-1 receptor agonist, markedly potentiated bifemelane- and bromocriptine-induced yawning but inhibited physostigmine-induced yawning, and did not affect pilocarpine-induced yawning. The increased yawning responses were blocked by atropine and a low dose of haloperidol. Bifemelane (10 mg/kg) and bromocriptine (2.5 mg/kg) tended to increase apomorphine (5 mg/kg)-induced oral stereotypy, such as licking and biting, but the increase was not significant. These results suggest that the effects of bifemelane on central dopaminergic and cholinergic neurons may be similar to those of bromocriptine. PMID- 2907958 TI - [Neuromodulation by second messengers]. PMID- 2907959 TI - Psychopharmacological analysis of hypothalamically-induced emotions. AB - The effect of minor tranquilizers and neuroleptics was compared on self stimulation and escape behaviourelicited by electrical stimulation of the hypothalamic nuclei in rabbits. It was shown that while tranquilizers (diazepam, oxazepam and meprobamate) increased the rate of self-stimulation elicited from the lateral hypothalamus, neuroleptics considerably suppressed such behaviour. Tranquilizers caused a remarkable reversal of the escape behaviour into a high rate self-stimulation, both responses being induced from the same electrodes within the medial hypothalamus. Neuroleptics (chlorpromazine, reserpine and haloperidol) had not such an influence, though they somewhat increased the general activity of the animals. The reversing effect of the tranquilizers was compared with similar findings obtained after electrolytic ablation of the ventral hippocampus. It is suggested that the hippocampus has an inhibitory influence on the hypothalamic motivational system thus providing substantially for the animals' survival in a hostile environment. PMID- 2907960 TI - The effects of different receptor blockers on the H-Phe-Ile-Tyr-His-Ser-Tyr-Lys OH induced inhibition of extinction of active avoidance behaviour. AB - H-Phe-Ile-Tyr-His-Ser-Tyr-Lys-OH after intracerebroventricular (icv.) administration inhibited the extinction of active avoidance behaviour for a short period. The dopamine receptor blocker haloperidol completely blocked this effect of the heptapeptide, while the muscarinic anticholinergic agent atropine only partly inhibited it. The alpha 1-receptor blocker phenoxybenzamine and the beta receptor blocker propranolol did not significantly influence the extinction inhibition induced by the peptide. These results suggest that the dopaminergic and, in part the cholinergic system, play important roles in this behavioural action of H-Phe-Ile-Tyr-Ser-Tyr-Lys-OH. PMID- 2907961 TI - Somatostatin in the control of respiration. AB - Somatostatin has been found to induce apnoea when applied into the brain ventricular system (Fuxe et al. 1982, Harfstrand et al. 1985). The site of action of somatostatin was suggested to be in the dorsal respiratory neurons in the medulla oblongata of the rat (Fuxe et al. 1982) where high somatostatin-like immunoreactivity has been detected (Kalia et al. 1984a). In the present study we wanted to further localize the site(s) of action of somatostatin on respiration by microinjection of somatostatin into the medulla oblongata of the cats. We could not detect any inhibitory effect of somatostatin on respiration after microinjection into the nuclear complex of the solitary tract. On the other hand microinjection of somatostatin into the region of nucleus paragigantocellularis lateralis consistently caused apnoea. This finding further supports the idea that this structure functions as an integrative area of respiratory drive inputs. PMID- 2907962 TI - Neuropeptide Y may inhibit sympathetic transmitter secretion by an effect 'upstream' of varicosities. PMID- 2907963 TI - Hematologic and immunologic changes in hairy cell leukemia patients treated with alpha interferon. AB - We prospectively evaluated hematologic and immunologic changes in fourteen hairy cell leukemia patients treated with alpha interferon. Prompt disappearance of circulating hairy cells, and recovery of peripheral blood counts was observed in all patients whereas only four patients had complete disappearance of hairy cell infiltrates from their bone marrow. Immunologic changes included a statistically significant increase of NK cell activity in the whole group and a slight decrease in circulating T cells with a strong trend towards an increase in the T4/T8 lymphocyte ratio (in eight of fourteen patients). Serial hemopoietic progenitor cell culture studies from peripheral blood (thirteen patients) and bone marrow (two patients) showed no correlation between hematologic recovery data and cell culture data. PMID- 2907964 TI - Regulation of enzyme levels by proteolysis: the role of pest regions. AB - Enzymes can be regulated in a variety of ways. Readily reversible mechanisms, such as phosphorylation, are frequently used by cells to control metabolic pathways. Less often, enzyme levels are regulated by changing the rate at which the protein is destroyed. Although these changes, too, are reversible through protein synthesis, large variations in enzyme concentration can be produced in very short periods of time by combinations of transcriptional control, translational control and rapid degradation. We recently examined the primary sequences of proteins whose intracellular half-lives are less than two hours. With a single exception, each short-lived protein contains one or more regions rich in proline (P), glutamic acid (E), serine (S) and threonine (T). These PEST regions range in length from 12 to 60 residues, and they are often flanked by possibly charged amino acids. Similar inspection of 35 more stable, structurally characterized proteins revealed only three weak PEST regions. All PEST proteins appear to be important regulatory molecules, and their fast turnover surely reflects a metabolic requirement for rapid changes in their concentrations. Known PEST proteins include oncogene products, key enzymes and components of signal pathways. In addition, there are a number of PEST-containing proteins that are suspected of being rapidly degraded. These proteins include Drosophila homeotic proteins (e.g., notch, snake, caudal, ftz and even-skipped) and a host of yeast cdc mutants. PEST regions, which target the molecules containing them for destruction, thus appear to be widely distributed among metabolically unstable proteins. PMID- 2907965 TI - Organization of repetitive DNAs in the guinea pig genome. AB - Investigation of restriction enzyme families observed in Bam HI and Eco RI digest of guinea pig DNA has led to the demonstration of a 4.0 kb cryptic satellite called MRICp which has 6300 copies and comprises 1% of the total genome. MRICp has been shown to encompass the Eco RI 4.0 kb family, the Bam HI 3.4 kb family and the Bam HI 3.7 kb family. The 1.5 kb Eco RI family is part of an L1 LINE that is present in the guinea pig and in other rodentia. It is part of a larger LINE, probably 6.5 to 7 kb in size, and some copies are embedded in satellite I DNA sequences. PMID- 2907966 TI - Studies on biomodulators of glucocorticoid action: amplifiers and suppressors of glucocorticoid action. AB - In this work we found that the induction of tyrosine aminotransferase by glucocorticoid in rat hepatocytes was suppressed concentration-dependently by TGF beta and H-7, an inhibitor of protein kinase C, but not by other polypeptide growth factors tested or by H-8, an inhibitor of cyclic nucleotide dependent protein kinases. EGF, on the contrary, amplified the induction in the same way as activators of protein kinase C, such as 12-o-tetradecanoyl-phorbol 13-acetate (2,3) and 1,2-racemic dioctanoyl glycerol (1,3). These findings indicate that TGF beta and H-7 act in the suppressive direction and EGF acts in the enhance direction on the action of glucocorticoid. H-7 inhibited the accumulation of glucocorticoid-receptor complexes in the nuclear fraction with associated accumulation of these complexes in the cytoplasmic fraction, but did not affect incorporation of glucocorticoid into hepatocytes. These results suggest that protein kinase C is essential in translocation of glucocorticoid-receptor complexes to the nuclei and that its inhibitors suppress glucocorticoid actions. PMID- 2907967 TI - Programmed cell death and adenine deoxynucleotide metabolism in human lymphocytes. AB - Agents that cause the accumulation of DNA strand breaks are directly cytotoxic to non-dividing normal human peripheral blood lymphocytes, and to chronic lymphocytic leukemia (CLL) cells. Activation of poly(ADP-ribose) polymerase (ADPRP), and the resultant consumption of NAD, play an essential role in mediating the toxicity of these agents. Human peripheral blood lymphocytes contain a substantial number of alkali-sensitive DNA sites, reflecting ongoing DNA strand breakage and repair. However, resting lymphocytes have a limited capacity to synthesize NAD. Pulse-chase experiments indicate that approximately 75% of their NAD turnover is due to ADPRP activity. Exposure of the cells in vitro to deoxyadenosine, or to 2-chlorodeoxyadenosine (CdA, an adenosine deaminase resistant deoxyadenosine congener), caused an increase in DNA strand breaks, rapid NAD consumption, ATP depletion and cell death. Supplementation of the medium with inhibitors of poly(ADP-ribose) polymerase blocks the fall in cellular NAD and ATP, and protects the lymphocytes from the toxicity of DNA damaging agents. Slowly dividing malignant lymphocytes from patients with CLL are also susceptible to lethal NAD depletion following DNA damage. 2 chlorodeoxyadenosine (CdA) induced massive DNA strand break formation in CLL cells in vitro and a fall in NAD and ATP pools. In an initial clinical trial, several CLL patients, and two patients with hairy cell leukemia, have responded to treatment with CdA, with minimal toxicity. Thus, the suicidal activation of ADPRP in response to DNA damage has been rationally exploited in the treatment of chronic lymphoid malignancies. PMID- 2907969 TI - [Prenatal diagnosis using DNA analysis: current possibilities]. PMID- 2907968 TI - Enzyme-pattern-targeted chemotherapy with tiazofurin and allopurinol in human leukemia. AB - The hypothesis was tested that the increased IMP dehydrogenase activity in human myelocytic leukemic cells, and along with it guanylate biosynthesis, might be a sensitive target to chemotherapy by tiazofurin. 1. IMP dehydrogenase activity in normal leukocytes was 3.1 +/- 0.5 (means +/- S.E.) nmol/hr/mg protein and in leukemic cells it was elevated 15- to 41-fold. The activity of guanine phosphoribosyltransferase in normal leukocytes was 389 +/- 27 nmol/hr/mg protein and in the leukemic cells it increased 2.8- to 6.8-fold. 2. IMP dehydrogenase was purified 4,900-fold to homogeneity from rat hepatoma 3924A with a yield of 30%. The kinetic properties of the hepatoma enzyme were similar to those of the enzyme in human myelocytic leukemic blast cells because of the similarity of the Km's for IMP (23 microM), NAD (44 and 65 microM); the Ki for TAD was 0.1 microM in both enzymes. 3. There was a selectivity of the in vitro response to tiazofurin in human normal and leukemic leukocytes. When labeled tiazofurin was incubated with leukocytes from normal, healthy volunteers and from leukemic patients, the leukemic leukocytes made 20- to 30-fold more TAD and the GTP content decreased as compared to normal leukocytes. This procedure proved to be a suitable predictive test in a clinical setting because patients with positive tests responded to tiazofurin whereas those with negative ones did not. 4. The National Cancer Institute approved a chemotherapeutic phase I/II trial which concentrates on treatment of refractory acute myelocytic leukemia. Tiazofurin is infused in a 60 minute period with a pump to insure uniform delivery. A novel aspect of the trial was that it was directed primarily by the biochemical impact of tiazofurin on IMP dehydrogenase activity and GTP concentration and the tiazofurin doses were to be adjusted accordingly. Patients received allopurinol as a routine precaution against possible accumulation of uric acid in the kidney. 5. In the first eight patients, there was one complete remission, two entered the chronic phase, two entered into partial remission, one did not respond, and two were not evaluable. In the five patients who responded, there was a rapid, profound decrease in IMP dehydrogenase activity of the blast cells and a gradual decline in GTP concentrations. The blast cell count followed the decrease in the GTP concentration. The white blood cell count was largely preserved. 6. Bone marrow aspirates and peripheral blood samples showed that with tiazofurin treatment there was an induced differentiation of the myelocytes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2907970 TI - [Psycho-pharmacologic profile of para-hydroxybenzonitrile]. PMID- 2907971 TI - Oxidative modification of enzymes during aging and acute oxidative stress. PMID- 2907972 TI - Oxidative modification of glutamine synthetase: covalent and conformational changes which control susceptibility to proteolysis. PMID- 2907973 TI - Oxidative modification of enzymes by stimulated neutrophils. PMID- 2907974 TI - [Internal resorption: from diagnosis to clinical problems]. PMID- 2907975 TI - The H+-ATPase from yeast plasma membranes; a survey of recent progress. PMID- 2907976 TI - [Microbial contamination of traditional herbal drugs in Indonesia]. PMID- 2907977 TI - The expression of schizophrenia, affective disorder and vulnerability to tardive dyskinesia in an extensive pedigree. AB - The demography, psychiatric morbidity, and motor consequences of long-term neuroleptic treatment in the 14 children born to a father with a family history of chronic psychiatric illness and a mother with a late-onset affective disorder resulting in suicide are documented. Twelve siblings lived to adulthood, nine of whom were admitted to a psychiatric hospital in their second or third decade, and required continuous in-patient care; five remaining in hospital, with long-term exposure to neuroleptics, had chronic, deteriorating, schizophrenic illness and emergence of movement disorder. Two siblings showed no evidence of psychosis but developed a late-onset affective disorder. The implications for the issues of homotypia, vulnerability to involuntary movements, and interaction with affective disorder are discussed. PMID- 2907978 TI - Preventive measures for stress ulcers in burn patients. AB - Between January 1981 and December 1985 336 patients with deep partial and full skin thickness burn injuries covering more than 20 per cent of the body surface area (BSA) were treated in our burn unit. During the first 3.5 years prophylactic therapy for stress ulcers consisted of cimetidine or ranitidine whereas during the last 18 months a combination of ranitidine and sucralfate was used. Over the whole period a protein-rich enteral feeding was instituted as early as possible after injury. Six times 200 mg/day cimetidine were administered intravenously during the first 4-6 days after injury, followed by a reduction to 4 x 200 mg/day usually until the end of the third week. Subsequently cimetidine was given orally in doses of 5 x 200 mg/day. Ranitidine (3 x 112 mg) was given intravenously until enteral feeding started, usually for the first 4 days, after oral nutrition had started the dosage was reduced to 3 x 56 mg/day. Over the past 18 months 4 x 1 g/day granular powdered sucralfate in combination with 3 x 56 mg/day ranitidine were given. The incidence of gastrointestinal bleeding was 2.5 per cent and no patient required surgical therapy. With respect to prophylaxis of bleeding and perforation of stress ulcers the triple regimen using sucralfate, ranitidine in low dosages and protein-rich enteral feeding appeared to be as effective as the earlier use of cimetidine or ranitidine. Side-effects of H2-blockade treatment, especially the high incidence of pneumonias caused by ascending infection from the gastrointestinal tract, were not seen. The high incidence of diarrhoea during H2-blockade treatment in combination with high protein enteral feeding remains to be solved. PMID- 2907979 TI - [Neurotransmitters of giant neurons in the African giant snail, Achatina fulica Ferussac. IV. Supplemental results]. AB - Following the previous works, we identified recently the twelve giant neurones in the ganglia of an African giant snail (Achatina fulica Ferussac), by the pharmacological study of their sensitivities to putative neurotransmitters and derivatives, and by the morphological investigation of their axonal pathways due to the intracellular injection of Lucifer Yellow. The neurones studied were: TAN 2, TAN-3, BAPN, LPPN, LBPN and LAPN in the right parietal ganglion; RPeNLN and LPeNLN in the pedal ganglia; and d-LBAN, d-LBMN, d-LBCN and d-LBPN in the left buccal ganglion. PMID- 2907981 TI - [Long-term study of befunolol in the treatment of open-angle glaucoma]. PMID- 2907980 TI - [Chorioretinal manifestations in periarteritis nodosa apropos of 2 cases]. PMID- 2907982 TI - [Role of antihistaminics in the treatment of allergic conjunctivitis]. PMID- 2907983 TI - A longitudinal study of serum beta 2-microglobulin levels in haemophilia. AB - Serum beta 2-microglobulin (beta 2-m) levels were measured in 75 adults with haemophilia A. Beta 2-microglobulin was found to be significantly elevated in haemophiliacs compared with the non-haemophiliac population. There was a greater rise in beta 2-m in HIV antibody-positive haemophiliacs. No further significant increase occurred in the subgroup with HIV-related disease but all these patients had beta 2-m levels greater than or equal to 3 mg/l. Over the study period of 18 months no significant increase in beta 2-m was documented in either HIV antibody negative or -positive groups. Beta 2-microglobulin was elevated in HIV antibody negative subjects with raised transaminase levels. No correlation was found between beta 2-m and the amount of factor VIII concentrate infused, T-cell subsets, thrombocytopenia or age. It is concluded that probable reasons for elevated beta 2-m levels in haemophiliacs include infection with HIV and other viruses, chronic liver disease, and repeated antigenic challenge from multiple infusions of factor VIII. The role of serial measurement of beta 2-m in haemophiliacs with a view to predicting the onset of HIV-related disease warrants further study. PMID- 2907984 TI - Detection of arylsulfatase A in leukocytes and urines of late infantile metachromatic leukodystrophy. Report of 3 cases. PMID- 2907985 TI - [Anti-alcoholic effect of the opioid peptide dermorphin in rats and its interaction with brain biogenic amine metabolism]. PMID- 2907986 TI - Homeobox genes and the vertebrate head. AB - Several Drosophila genes important in the control of embryonic development contain a characteristic sequence of DNA, known as the homeobox. Homeobox sequences are also present in a family of vertebrate genes, which may therefore have regulatory roles during vertebrate embryogenesis. In this article, data concerning the spatial patterns of vertebrate homeobox gene expression are discussed in relation to recent descriptive and experimental analyses of head development. It is concluded that the patterns of gene expression are consistent with homeobox genes having roles in anteroposterior positional specification within the developing brain and possibly the neural crest. The data are not clearly consistent with these genes having direct roles in controlling the patterns of cranial segmentation, although further studies may reveal whether vertebrate segments are units of developmental specification. PMID- 2907987 TI - Transient neonatal hypothyroidism due to transplacental transfer of maternal immunoglobulins that inhibit TSH binding, TSH-induced cAMP increase and cell growth. AB - Transient neonatal hypothyroidism due to transplacental transfer of maternal blocking type TSH receptor antibodies (TRAb) was found in a baby born to a 27-yr old mother, who had been receiving thyroxine medication for primary myxedema. Maternal IgG inhibited radiolabelled TSH binding to its receptor (TBII), TSH stimulated thyroid adenylate cyclase (AC) activation (TSII) and TSH-stimulated 3H thymidine uptake (TGII) in cultured rat thyroid cells (FRTL-5). At birth, the baby's IgG showed similar activities to maternal IgG but all these activities decreased gradually, and disappeared from her serum within 12 weeks of age. In the baby, initially nonvisualized thyroid was clearly visualized on 99 m-Tc thyroid scintigraphy when all these blocking activities disappeared, TSII and TGII being decreased more slowly than TBII, and the baby remained euthyroid after discontinuation of thyroxine. This study suggests that such IgGs induced hypothyroidism and thyroid atrophy in the mother and were responsible for transient neonatal hypothyroidism in the baby. PMID- 2907988 TI - Effect of thyrotropin releasing hormone injection on blood growth hormone (GH), TSH and growth hormone releasing hormone (GHRH) concentrations in cancer patients. AB - In order to investigate whether endogenous GHRH and somatostatin were involved in the mechanism of the paradoxical GH rise after TRH injection, changes in serum GH and plasma GHRH were examined before and after TRH injection in 12 cancer patients and changes in serum TSH and GH were similarly studied in 76 cancer patients including 31 GH-responders and 45 GH-nonresponders to TRH. TRH stimulated GH secretions without altering the circulating GHRH concentration in 4 of the 12 cancer patients. There was neither a significant correlation between the increase from the basal to maximum GH and GHRH after TRH injection in the 12 cancer patients nor a reciprocal relationship between the increase in GH and TSH after TRH injection in the 76 cancer patients. These findings suggested that the paradoxical GH rise after TRH injection in cancer patients was exerted by its direct action at the pituitary level, and not mediated through the hypothalamus. PMID- 2907989 TI - [Soldering after firing silver-free gold-palladium and palladium based fired alloys]. PMID- 2907990 TI - [Laser stream sweating--an upcoming technology for the dental laboratory]. PMID- 2907991 TI - [Plasma soldering or soldering? Dimensional accuracy and stability]. PMID- 2907992 TI - Subcutaneous treatment with growth hormone-releasing hormone for short stature. AB - In the present study we report the effects of therapy with growth hormone releasing factor (1-29)NH2 (GRF) on growth rate, plasma levels of insulin growth factor I (IGF-I) and growth hormone (GH) secretion in 11 children who were selected solely on the basis of their short stature and normal GH secretion on standard provocative tests. All children received GRF for 6 months (5 micrograms/kg body weight subcutaneously) each evening. The 24-hour GH secretory profile was studied before and after 6 months of treatment. Simultaneously, GH secretory responses to single intravenous bolus GRF (1.5 micrograms/kg body weight) were also studied before, during, and 6 months off therapy with GRF(1 29)NH2. Plasma levels of IGF-I were measured before, during (1, 2 and 6 months), and after 6 months off therapy with GRF. Statural growth was measured at 3-month intervals. The peak plasma GH level in response to GRF was 56.04 +/- (SD) 24.46 ng/ml before treatment, and similar results were found after therapy. The 24-hour GH secretory profile did not show differences before, during, and after treatment. Comparably, no differences were found in GH pulse frequency, pulse amplitude, pulse height, pulse increment, pulse area and total area before, and 6 months off therapy with GRF. The increments in serum IGF-I achieved were not significantly different at all intervals studied. All patients increased growth velocities (mean +/- SD, cm/year) in response to GRF therapy. Our results demonstrate that GRF administration was effective in accelerating growth velocity in 11 children without GH deficiency. PMID- 2907993 TI - Medical education and the IMA. PMID- 2907995 TI - [Recent trend in the research of hypertension in Japan. Choice of antihypertensive agents in hemodynamic aspects to match pathophysiology and pharmacology in essential hypertension]. PMID- 2907994 TI - Differential expression of the ASGM1 antigen on anti-reovirus and alloreactive cytotoxic T lymphocytes (CTL). AB - Anti-reovirus cytotoxic effectors were found to be: (i) H-2 restricted; (ii) virus specific; (iii) non-lytic (in 4 h) for natural killer (NK)-sensitive YAC-1 cells; and (iv) positive for the Thy-1 and Lyt-2 lymphocyte markers. Thus, anti reovirus cytotoxic effectors have the functional and phenotype characteristics of cytotoxic T lymphocyte (CTL). A significant fraction of anti-viral CTL, as well as alloreactive CTL, were also found to be positive for the asialo GM1 (ASGM1) cell surface antigen, generally considered to be a NK cell marker. ASGM1 expression on these CTL, as determined by sensitivity to antibody plus complement (C), appeared to be highly variable and dependent on two factors-the nature of the antigenic stimulus (viral vs. alloantigen), and the mouse strain from which the CTL originated. Thus, ASGM1 antigen expression on CTL appears to be regulated and may be under the control of lymphokines, development differentiation signals and/or other strain-dependent genetic factors. PMID- 2907996 TI - [Recent trend in the research of hypertension in Japan. The effects of antihypertensive drugs on serum lipids and lipoproteins in patients with mild to moderate hypertension]. PMID- 2907997 TI - A molecular deletion study with southern hybridization on typical Prader-Willi syndrome (PWS) patients with various chromosome abnormalities involving 15q11-12 and on an atypical PWS patient with apparently normal karyotype. PMID- 2907998 TI - [Gamma-glutamyltranspeptidase in occupational exposure to hepatotoxic material and certain diseases]. PMID- 2907999 TI - Mass and activity of tyrosine hydroxylase in tuberoinfundibular dopaminergic neurons of the aged brain. Control by prolactin and ovarian hormones. AB - The roles of prolactin (PRL) and the ovarian hormones, estradiol and progesterone, in the control of tuberoinfundibular dopaminergic neurons of aged female rats were investigated. The in situ molar activity of tyrosine hydroxylase (TH) in neurites of these neurons was assayed by measuring the rate of accumulation of L-dihydroxyphenylalanine in the median eminence following the administration of a L-dihydroxiphenylalanine decarboxylase inhibitor. The TH mass was measured by an immunoblot assay using rat TH as the standard. Pituitary implants in aged ovariectomized animals resulted in a significant increase in the median eminence of both the mass and in situ molar activity of TH. When circulating PRL of aged rats was neutralized by administration of antiserum against rat PRL, the activity of TH was reduced significantly compared to that of animals treated with preimmune serum. In aged ovariectomized rats treated with both estradiol and progesterone, the in situ molar activity of TH increased significantly compared to animals treated only with the solvent vehicle, estradiol, or progesterone. The stimulatory effect of estradiol and progesterone appeared to be mediated through a mechanism that did not involve PRL, since neutralization of circulating PRL failed to prevent an increase in TH activity in estradiol-progesterone-treated animals. None of these treatments affected the in situ activity of TH in the superior cervical ganglion. We conclude that PRL as well as combined estradiol-progesterone treatment have important roles in the maintenance of TH activity in aged tuberoinfundibular dopaminergic neurons. PMID- 2908000 TI - Corticotropin-releasing factor: evidence for a neurotransmitter role in the locus ceruleus during hemodynamic stress. AB - Corticotropin-releasing factor (CRF) is localized in fibers in the noradrenergic nucleus locus ceruleus (LC) and alters LC discharge characteristics when administered centrally. To determine whether CRF functions as a neurotransmitter in the LC during stress, the effects of hemodynamic stress on LC discharge were compared to those of CRF. Hemodynamic stress elicited by intravenous nitroprusside infusion produced identical effects on LC spontaneous and sensory evoked discharge as those reported for centrally administered CRF. Thus, nitroprusside increased LC spontaneous discharge rates, and disrupted LC discharge evoked by sensory stimuli such that the stimuli were less effective in producing phasic increases in LC discharge. The neuronal effects of nitroprusside were completely blocked by central administration of the CRF receptor antagonist, alpha helical CRF9-41, but not by pretreatment with dexamethasone which blocks stress-elicited hypophyseal CRF release. The present results confirm other reports of LC activation by stressors, and extend these studies by demonstrating that, in certain circumstances, this activation is dependent on endogenous CRF. This study supports the concept that CRF functions as a neurotransmitter in the LC in the initiation of stress responses. PMID- 2908001 TI - [Interactions of cimetidine and ranitidine with other drugs]. PMID- 2908002 TI - Aging: changes in a passive-avoidance response with brain levels of temazepam. AB - Acute intravenous (IV) injections of temazepam were examined for the ability to impair the performance of young (3-4-month-old), mature (12-15-month-old) and old (28-30-month-old) male Fischer 344 rats in the step-down task relative to vehicle injected controls. The effect of temazepam on the passive-avoidance response could be characterized as a U-shaped function of age. The performance of the mature rat was not significantly impaired by an IV injection of temazepam between 18 and 320 micrograms/kg. Temazepam was more effective in impairing the performance of the young and old rat. The brain levels of temazepam after a single IV injection of 18 micrograms/kg in mature and senescent rats, and 32 micrograms/kg in young rats were measured over a 2-hour time period. The brain of the mature rat was exposed to less temazepam between 0 and 120 minutes than the brain of the old rat. Therefore, the increased sensitivity of the senescent rat relative to the mature rat may in part be due to changes in the pharmacokinetics of temazepam. However, the inability of temazepam (between 18 and 320 micrograms/kg) to impair the performance of mature rats in the passive-avoidance task suggests that pharmacodynamic changes may be involved in the decreased sensitivity of mature rats relative to young and senescent rats. PMID- 2908003 TI - Intravenous self-administration of the indirect dopaminergic agonist amfonelic acid by rats. AB - The reinforcing properties of amfonelic acid, a nonamphetamine psychostimulant, were evaluated in an intravenous self-administration paradigm. Rats were trained to self-administer cocaine (0.5-3.0 mg/kg/infusion) on a fixed-ratio 10 schedule of reinforcement via surgically implanted intravenous catheters during daily 4-hr sessions. Substitution of amfonelic acid (0.0625-0.250 mg/kg/infusion) reliably maintained self-administration in a dose-dependent manner. These data indicate that amfonelic acid can act as a reinforcer in rats, and further suggest that amfonelic acid may have abuse potential in humans. PMID- 2908004 TI - [Changes in brain level of neurotransmitters in Alzheimer's disease]. PMID- 2908005 TI - [Inactivation of enzymes by active oxygen]. PMID- 2908006 TI - [Atrial natriuretic factor--a new neuropeptide?]. PMID- 2908007 TI - Hepatic hematoma in polyarteritis nodosa. PMID- 2908008 TI - Alpha adrenergic blocking activity of urapidil in man. AB - Urapidil is a new antihypertensive vasodilator agent whose pharmacologic action in man has not yet been fully defined. We have assessed the alpha adrenergic blocking activity of urapidil 15 and 30 mg given intravenously in a single blind study in 8 healthy volunteers. Urapidil produced dose-dependent parallel shift of the phenylephrine log dose/blood pressure response curve, consistent with significant competitive peripheral alpha 1 antagonism. Mean dose ratios were 2.99 and 5.48 for the 15 mg and 30 mg doses respectively. The pA2 for alpha 1 blockade is 7.3. Given these data, the major mechanism of antihypertensive effect of urapidil may be alpha 1 antagonism in the peripheral vasculature. PMID- 2908009 TI - Structural specificity of MIF-1 and Tyr-MIF-1 in augmenting GABA-stimulated benzodiazepine receptor binding. AB - The possibility of a linkage between endogenous peptides and the GABA benzodiazepine system has been greatly strengthened by reports that the brain peptides MIF-1(Pro-Leu-Gly-NH2) and Tyr-MIF-1(Tyr-Pro-Leu-Gly-NH2) augment GABA stimulated benzodiazepine binding. We evaluated the actions of fragments and analogs of these small peptides on GABA-stimulated benzodiazepine binding in mouse cortical brain membranes. Fragments of Tyr-MIF-1, several compounds related to MIF-1, or several analogs of Tyr-MIF-1 had no effect on binding. These results demonstrate the specificity of the effects of MIF-1 and Tyr-MIF-1 on GABA stimulated benzodiazepine binding. PMID- 2908010 TI - Immune mediated cartilage destruction. AB - We review the pathogenic role of immune complexes attached to articular cartilage in rheumatoid arthritis. The available evidence suggests that these immune complexes may contribute to irreversible cartilage damage and loss of joint function. In addition, tenacious binding of these complexes to collagenous tissues, possibly by the establishment of covalent bonds, may constitute an important chronicity factor in this disease. The biochemical mechanisms that may be responsible for covalent cross-linking of macromolecules in inflammatory foci are discussed. PMID- 2908012 TI - [New aspects of beta blocker therapy. Pharmacologic data and therapeutic value. Satellite symposium of the European Cardiology Congress. 3 September 1988, Budapest. Abstracts]. PMID- 2908011 TI - [Antihypertensive drugs and the kidney]. PMID- 2908013 TI - [Ulcerative colitis in children. Levels of salicylazosulfapyridine and sulfapyridine during treatment]. AB - Salicylazosulfapyridine (SASP) is a drug used in the treatment of ulcerative colitis (UC) owing to the therapeutic action of the 5-aminosalicylic acid produced by the splitting of the molecule in the cecum, which also yields the absorbable compound Sulphapyridine (SP). The aim of our work was to assess the levels of the drug in blood (SASP and SP), to correlate them with undesirable effects in any, to verify their fluctuations in the dosing interval and to investigate the extent of the excretion of the drug in the children who were studied. 10 children (6 to 16 years) with UC, who were treated with SASP (dOsage schedule 0.5-2.0 g/day in a 12 hours interval), were studied. Blood levels of SASP and SP were assessed at 6 and 12 hours after doses, and total fecal excretion of SASP was determines in 24 hs specimens. All the determinations were performed according to Hansson and Sandberg. SP plasma levels were 17.7 +/- 9.0 ug/ml (range 6.8-36.3 ug/ml) at 6 hours after doses. and 14.1 +/- 7.2 ug/ml (range 5.7-25.0 ug/ml) at 12 hours after doses. SASP plasma levels were 15.5 +/- 15.4 ug/ml (range 2.1-53.4 ug/ml) at 6 hours after doses, and 14.0 +/- 20.4 ug/ml (range 3.9-70.7 ug/ml) at 12 hours after doses. The 24 hours fecal excretion was 17.4 to 236 mg. These values were correlated with the given doses (r = 0.88) calculated as SASP g/m2 body surface 24 hs. There was no statistical correlation between doses and SP or SASP levels in this group, and the respective levels of SASP and SP at 6 and 12 hours after doses showed no significative differences.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2908014 TI - Neurotransmitter systems in the visual cortex of the cat: possible involvement in plastic phenomena. AB - The aim of this paper is to review some of the investigations on neurotransmitter systems suggesting their possible role in visual information processing and their putative involvement in the plastic phenomena observed in the primary visual cortex of the cat. The neurotransmitters discussed include excitatory amino acids, ?-amino-butyric acid, acetylcholine, noradrenaline and serotonin. The following problems are discussed: (i) the occurrence and localization of the various neurotransmitter system components, (ii) the developmental changes of the components of a given neurotransmitter system, particularly in the critical period, (iii) the effects of manipulating the visual input on neurotransmitter system markers. It seems that especially during the critical period there exists a peculiar pattern of interactions between numerous neurotransmitters and neuromodulators. This may create unique conditions, which enable the visual cortical neurons to change their properties as a results of alterations of the visual input. PMID- 2908015 TI - Potency of antipsychotics in reversing the effects of a hallucinogenic drug on locus coeruleus neurons correlates with 5-HT2 binding affinity. AB - Systemic administration of the phenethylamine hallucinogen 2,5-dimethoxy-4 methylamphetamine (DOM) has previously been shown to decrease spontaneous activity but increase the response to peripheral nerve stimulation of locus coeruleus (LC) neurons in anesthetized rats. Five antipsychotic drugs (spiperone, chlorpromazine, clozapine, haloperidol, and sulpiride) were tested for their ability to antagonize these effects of DOM in the LC. Spiperone, chlorpromazine, clozapine, and haloperidol were able to completely reverse the effects of a standard dose of DOM, while sulpiride was ineffective. The ED100s for reversing the effects of DOM showed a significant correlation only with the previously shown binding affinity for 5-HT2 receptors. These results suggest that certain types of antipsychotic drugs have activity as 5-HT2 antagonists in vivo. PMID- 2908016 TI - Seven-year follow-up of tardive dyskinesia in Hungarian outpatients. AB - Of 122 Hungarian outpatients treated with neuroleptics, 79 (64.8%) were available for follow-up 7 years after their original assessment for tardive dyskinesia (TD). Ratings on the Abnormal Involuntary Movements Scale and the Simpson Dyskinesia Rating Scale increased significantly. The number of TD cases identified by research diagnostic criteria increased by only 9%: 12 of 28 patients no longer showed TD 7 years later, while 19 of 51 patients developed new TD. PMID- 2908018 TI - Psychotogenic drugs as models for schizophrenia. PMID- 2908017 TI - New insights into schizophrenia through atypical antipsychotic drugs. PMID- 2908019 TI - Effects of prenatal exposure to neuroleptic drugs on children's growth. AB - The effect of prenatal exposure to neuroleptic drugs on height and weight from birth to 7 years was examined in children of psychiatrically normal parents and of parents with a history of psychiatric treatment, using data from the Collaborative Perinatal Project of the National Institute of Neurological Diseases, Communicative Disorders, and Stroke. Analysis of covariance was used to control for potential confounding factors. We found that prenatal exposure to dopamine receptor-blocking neuroleptic drugs was associated with increased height in one or more of our groups at 4 months, 1 year, and 7 years and less consistently with increased weight. Seven-year-old children who had been exposed to these drugs for more than 2 months during gestation were approximately 3 cm taller than unexposed controls (p less than 0.05). Prenatal exposure to dopamine depleting agents was associated with decreased height at 4 months but not later. Possible mechanisms for these effects, including a permanent decrease in the number of brain dopamine receptors and effects on various hormones, are discussed. PMID- 2908020 TI - Subjective effects of 3,4-methylenedioxymethamphetamine in recreational users. AB - 3,4-Methylenedioxymethamphetamine (MDMA; Ecstasy) is a serotonergic neurotoxin in laboratory animals that has been used for recreational purposes by humans. The subjective effects of this drug were determined in recreational users at a university campus. Of individuals who had admitted to using MDMA recreationally, 100 of 143 agreed to complete a detailed questionnaire concerning the subjective effects of this Schedule I compound. The most common effect of MDMA was a heightened sense of "closeness" with other people (90% of subjects). Tachycardia, dry mouth, bruxism and/or trismus were reported by the majority of users. These effects probably result from the amphetaminelike properties of the drug. Visual hallucinations were reported by 20% of users. Untoward side effects were most common on the day following the use of MDMA, with complaints of muscle aches, fatiguability, depression, and difficulty concentrating noted by 21% to 36% of subjects. Sixty-seven percent of frequent users of the drug (six or more separate doses) reported that the "positive" effects of the drug decreased with successive doses while the "negative" effects increased. Although these observations should be considered preliminary, they represent the first documentation of the subjective effects of MDMA in recreational users and confirm previous reports obtained from patients treated with this drug. PMID- 2908021 TI - Altered activity of the locus coeruleus in an animal model of depression. AB - In rats showing depression of active behavior, locus coeruleus (LC) neurons were not inhibited as they are normally; in particular, electrophysiologic recording showed LC neurons were hyperresponsive to excitatory input. Moreover, the degree to which LC neurons of individual animals were hyperresponsive correlated positively with the degree to which active behavior was depressed. Recently, hyperresponsiveness of LC neurons has been found to occur when the inhibitory influence of alpha 2-receptors on LC firing is blocked. Pharmacologic blockade of alpha 2-receptors in animals showing behavioral depression was not able to increase responsiveness of LC neurons as in normal animals, indicating that alpha 2-receptors were subnormally activated in behavioral depression. These results show that activity of the principle noradrenergic cell group in the brain, the locus coeruleus, is altered in behavioral depression in an animal model, and suggest that abnormalities in this system and its regulatory elements, such as alpha 2-receptors, may be present in some types of clinical depression. PMID- 2908022 TI - Spatial regulation of homeo box gene expression in Drosophila. AB - 1. Each of the 17 known homeo box genes shows a unique pattern of expression during early embryonic development. Thus, virtually every embryonic cell contains a unique combination of active and inactive homeo box genes. 2. These different permutations of homeo box gene expression are thought to specify unique positional values, and appear to play key roles in selecting diverse pathways of morphogenesis. 3. It has been proposed that selective patterns of homeo box gene expression involve cross-regulatory interactions. For example, it appears that homeotic genes expressed in posterior regions of the embryo (such as abd-A and Abd-B) repress the expression of those homeotic genes expressed in more anterior regions (such as Antp and Ubx). Such interactions might involve sequence-specific DNA binding and occur at the level of transcription. 4. The establishment of selective patterns of pair-rule gene expression along the anterior-posterior embryonic body axis might involve the differential regulation of these genes by a common set of transcription factors. In particular, it appears that eve and ftz show opposite responses to regulatory products that are either directly or indirectly specified by several gap genes. PMID- 2908023 TI - The human apolipoprotein genes. AB - The apolipoproteins fall into two groups: the typical apolipoproteins (apo-AI, apo-AII, apo-AIV, apo-CI, apo-CII, apo-CIII and apo-E) constitute a multigene family with strong similarities in structure, genomic organization and in functional domains. The evolutionary relationship of these genes has been particularly well studied. Important work is now under way to analyse genetic variation of the apolipoprotein genes which contributes to alterations in plasma triglyceride and cholesterol levels and enhanced risk of coronary heart disease. Intensive work is also focused on understanding apolipoprotein gene regulation and it is hoped that this will contribute to understanding how plasma lipid levels are determined. Apolipoprotein B produces two distinct proteins. These have a central role in lipid metabolism. Their structure has been analyzed from studies on cDNAs and the organization of the gene determined. It remains to be determined how the apo-B gene produces two proteins, the intestinal form being half the size of the hepatic form. Studies to date indicate that this is not by the usual mechanisms of exon shuffling or post-translational processing. It might be anticipated that the smaller form is produced by a novel mechanism. As with the other apolipoproteins intensive work is now focused on the analysis of genetic variation and of the study of apo-B gene variation. Analysis of the apo-B gene may have profound implications for the diagnosis and treatment of plasma lipid abnormalities. PMID- 2908024 TI - Homoeo box genes of the mouse. PMID- 2908025 TI - Evidence for a specific role for cortical NMDA receptors in slow-wave sleep. AB - Iontophoresis of the N-methyl-D-aspartic acid (NMDA) receptor antagonist 2-amino 5-phosphonovaleric acid (2-APV) was found to suppress spontaneous bursting activity of layer V cortical neurones during stage 3/4 sleep in unrestrained, normally behaving rats. Iontophoresis of NMDA, on the other hand, increased cortical burst durations and increased the number of spikes per burst. 2-APV was found not to alter cells' responses to tactile stimulation or the generation of neuronal spindling activity during stage 2 sleep. These results provide the first evidence that NMDA receptors subserve a specific function in the neocortex of the behaving animal, by gene-rating burst activity in cortical neurones during stage 3/4 of the natural sleep state. The activation of NMDA/2-APV-sensitive cortical receptors by afferents from the anterior intralaminar nuclei in the generation of bursts by cortical cells during stage 3/4 sleep is discussed. PMID- 2908026 TI - The origin of tyrosine hydroxylase-immunoreactive fibers in the regions of the nucleus basalis magnocellularis of the rat. AB - The simultaneous use of acetylcholinesterase (AChE) histochemistry and tyrosine hydroxylase (T-OH) immunocytochemistry permitted demonstration of the existence of a dense catecholaminergic network surrounding cholinergic neurons within the nucleus basalis magnocellularis (NBM) of the rat. The origin of this catecholaminergic network was investigated by combining T-OH immunocytochemistry with horseradish peroxidase (HRP) retrograde labelling using a slow release gel, unilaterally implanted in the area of the NBM. Retrogradely transported HRP was detected in some of the aminergic cell groups of the substantia nigra (A9) and locus coeruleus (A6). In these areas, approximately 1% of the tyrosine hydroxylase immunoreactive neurons were retrogradely labelled with HRP. In the substantia nigra, dually labelled neurons were found predominantly in the pars lateralis. PMID- 2908027 TI - Viral infection of neurons can depress neurotransmitter mRNA levels without histologic injury. AB - Neonatal mice inoculated with lymphocytic choriomeningitis virus (LCMV) have non lytic persistent neuronal infection and disturbed behavior. We now show that LCMV replicates in neurons containing the neurotransmitter somatostatin without morphologic evidence of injury and that persistent neuronal LCMV infection in mice is attended by a decrease in brain levels of somatostatin mRNA. Brain levels of mRNA for another neurotransmitter peptide, cholecystokinin, are not decreased. These data are the first to localize a virus to a specific neurotransmitter containing cell during in vivo infection and suggest that persistent viral infections could cause neurologic or psychiatric diseases through selective effects on brain levels of neurotransmitter mRNAs. PMID- 2908028 TI - Rostral ventrolateral medullary neurons with intrinsic pacemaker properties are not catecholaminergic. AB - Neurons of the rat rostral ventrolateral medulla with intrinsic pacemaker properties and immediately adjacent silent neurons were recorded in tissue slices, labeled intracellularly with the fluorescent dye Lucifer yellow, and the tissue was subsequently processed for the immunocytochemical detection of the catecholamine-synthesizing enzyme tyrosine-hydroxylase. Forty-five percent (9/20) of the silent neurons were tyrosine hydroxylase-immunoreactive, but none of the pacemaker cells were (0/15). We conclude that the ventrolateral reticular neurons with intrinsic pacemaker properties are not the C1 adrenergic cells. PMID- 2908029 TI - [Consequences of the use of beta-adrenergic agonists in the rearing of meat animals]. PMID- 2908030 TI - Long-term treatment with a new non-ergot long-acting dopamine agonist, CV 205 502, in women with hyperprolactinaemia. AB - Twenty-four hyperprolactinaemic women were treated for 6 months with the new, non ergot, long-acting dopamine agonist, CV 205-502. The treatment resulted in normalization of PRL secretion in 17 of the 24 women at once-daily doses of 0.05 to 0.15 mg of the drug. Sixteen of these women as well as 4 of those who remained hyperprolactinaemic had regular menstrual bleeding. Five of the patients had previously discontinued bromocriptine therapy because of adverse effects but had no problems tolerating CV 205-502. Of three bromocriptine-resistant women, two responded partially while one also remained unresponsive to CV 205-502 treatment. Mild to moderate galactorrhoea was recorded at baseline in 19 of the 24 women. After 6 months' treatment mild galactorrhoea was still present in six patients, four of whom had attained normal PRL levels. Side-effects were mild and transient. CV 205-502 seems to be a valuable compound in the management of patients with hyperprolactinaemia. PMID- 2908032 TI - Occurrence of traumatic injuries in the oromaxillary region of children in a Japanese prefecture. PMID- 2908031 TI - Studies on thyrotrophin receptor antibodies in patients with euthyroid Graves' disease. AB - Thyroid stimulating antibodies (TSAb) and TSH-binding inhibitor immunoglobulins (TBII) were assessed in 30 patients with euthyroid Graves' disease. TSAb were detected in 24 cases (80.0%), the incidence being not significantly different from that in hyperthyroid Graves' disease (29/30, 97.6%). On the other hand, the incidence of TBII in patients with euthyroid Graves' disease (12/30, 40.0%) was significantly lower than that in patients with hyperthyroid Graves' disease (30/30, 100.0%). The mean TSAb and TBII activities in the euthyroid patients were significantly lower than in the hyperthyroid patients (P less than 0.005 and P less than 0.001, respectively). Both TBII and, more closely, TSAb activities correlated with T3-nonsuppressibility and inhibition of serum TSH response to TRH stimulation. The findings supported the stimulation in vivo of the thyroid by these antibodies. Both antithyroglobulin and antimicrosomal antibody titres in euthyroid Graves' disease were significantly lower than in hyperthyroid Graves' disease (P less than 0.05, P less than 0.01, respectively). Goitre size was significantly smaller (P less than 0.001), and 99mTc thyroid uptake was significantly lower (P less than 0.001) in the euthyroid than in the hyperthyroid group. Thus, the reduced mass of thyroid tissues responding to the stimulators was considered to be one of the factors responsible for the euthyroidism despite the presence of TSAb. The high incidence of TSAb and relatively low incidence of TBII in euthyroid Graves' disease indicate that the presence of TSAb does not necessarily lead to hyperthyroidism and that the development of overt thyrotoxicosis may require augmentation of both TSAb and TBII. PMID- 2908033 TI - Somatostatin concentrations in discrete hypothalamic nuclei of genetically obese Zucker rats. AB - Hypothalamic somatostatin concentration was determined in 6.5 to 9 months old male and female genetically obese fatty (fa/fa) and lean (Fa/-) Zucker rats. Similar somatostatin levels were found in fatty and lean animals in the hypothalamic regions previously known to contain the highest hormone levels (median eminence and arcuate, periventricular and ventromedial nuclei). The fatty animals were grossly obese and had a pronounced hyperinsulinemia. PMID- 2908035 TI - [Use of services and treatment profile after the Psychiatric Reform Act]. PMID- 2908034 TI - Clinical experience with a radioreceptor assay for TSH-binding inhibiting immunoglobulins (TBII). AB - The aim of the present study was to evaluate the clinical value of a commercial kit for determination of TBII. Forty-seven of 50 patients with untreated hyperthyroid Graves' disease were TBII positive (sensitivity 94%). TBII was in the normal range in all normal volunteers and in patients with simple goiter, thyroid cancer and in most cases of nonimmunogenic hyperthyroidism (19 of 22). After 12 months antithyroid drug therapy with methimazole of 21 patients the prevalence of positive TBII findings was 28%. In contrast to this, 50 percent of the patients had increased microsomal antibodies at the end of therapy. The determination of TBII by TRAK-assay proved to be a sensitive, specific and practical method. The assay can be used to differentiate between hyperthyroidism of autoimmune or nonimmunogenic origin. Even so this method seems to be helpful for the follow-up during medical treatment of patients with Graves' disease. The results indicate that persistence of increased TBII levels are markers of active Graves' disease and suggest that in this situation ablative measures should be performed. Normalization of TBII on the end of a longstanding antithyroid therapy does not exclude the possibility of relapse in the further course. PMID- 2908036 TI - The use of oral contraceptives past the age of 35: bridging the gap. AB - With women deciding to delay pregnancy, there is an increasing need for safe contraception to bridge the gap until the onset of the menopause. Alternatives to guide the physician and the patient are summarized, and the safety and noncontraceptive benefit of low-dose oral contraceptives for women over the age of 35 is reviewed. PMID- 2908037 TI - Starting the new patient on oral contraceptives. AB - There are many considerations prior to starting a patient on oral contraceptives (OCs). A careful history and physical examination should be obtained, as should laboratory studies where indicated. In addition to the absolute and relative contraindications to OCs, the benefits should be reviewed with the patient. During therapy, the patient should be advised regarding potential minor side effects as well as serious signs and symptoms. There appears to be little difference in efficacy or side effects of monophasic vs. multiphasic contraceptives. It is recommended that a pill containing the lowest hormonal content, and thus with the least potential for side effects (ie, 35 micrograms of ethinyl estradiol), be utilized. PMID- 2908038 TI - Effects of oral contraceptives on the borderline NIDD patient. AB - With oral contraceptives (OCs), estrogen and progestogen doses, as well as the type of progestogen used, seem to directly affect glucose tolerance and insulin resistance. Other factors that influence these parameters are a patient's weight and age, family history of diabetes, and previous gestational diabetes. In normal weight women with previous gestational diabetes, low-dose OCs do not appear to directly affect glucose tolerance, plasma insulin levels, or insulin binding to monocytes. This paper reports the initial data from a study employing low-dose OC formulations in obese patients with a history of either Class A1 or A2 gestational diabetes. Although results are preliminary, they do suggest that Ovcon 35, a low-dose norethindrone-containing OC, may be safe in Class A1 diabetics; in Class A2 diabetics, Ovcon 35 is associated with significantly less change in oral glucose tolerance at 3 months than is the triphasic Triphasil. PMID- 2908039 TI - The effects of oral contraceptives on plasma lipids and lipoproteins. AB - It has been well documented that low-density lipoproteins and intermediate density lipoproteins play a role in the development of atherosclerosis. Data also indicate that high-density lipoproteins (HDLs), have potentially antiatherogenic effects. The individual estrogen and progestogen components of oral contraceptives (OCs) have been shown to affect plasma lipoproteins in both cross sectional and longitudinal studies. This effect depends on both the type of steroid used and the dose of each of the OC components. Estrogen and progestogen have opposing effects on lipoprotein physiology. Estrogens raise the level of HDL cholesterol, while progestogens tend to lower HDL levels. Thus, in OC formulations, as the ratio of estrogen to progestogen increases in favor of estrogen, there is a greater increase in HDL cholesterol--a potentially beneficial effect. Although there is no direct evidence that favorable lipoprotein changes produced by OCs are cardioprotective, the physician prescribing an OC should minimize adverse lipoprotein effects by prescribing a balanced low-dose, low-impact formulation. PMID- 2908040 TI - The androgenicity of progestational agents. AB - Androgenic potency of the progestational component in oral contraceptives (OCs) is difficult to assess. All the 19-nor testosterone progestogens in OC formulations basically have similar potencies and androgenic activities with the exception of norgestrel (NG). NG is the most potent and androgenic of these agents. It is five to ten times as potent as norethindrone (NET); levonorgestrel (1-NG), one of the two isomers of NG and the one responsible for its potency, is ten to 20 times more potent than NET. In addition, 1-NG is several times more androgenic than NET. However, when evaluating OC androgenic potency the antiandrogenic effect of the progestational agent as well as the effects of the estrogenic component have to be considered. Thus, it is useful to assess parameters that are affected by both OC components, such as changes in lipid levels. It may be concluded that given the potential deleterious metabolic effects produced by androgenic compounds, formulations should be used that have the least impact on these parameters. PMID- 2908041 TI - [Conclusions of the First Congress on Public Health and Sanitary Administration. Barcelona, October 1985]. PMID- 2908042 TI - Biologic factors in personality disorders. PMID- 2908043 TI - Long shelf-life of antigen-sensitised erythrocytes by double aldehyde stabilisation for the serodiagnosis of amoebiasis by indirect haemagglutination. PMID- 2908044 TI - Modified smooth muscle responses of jejunum in streptozotocin-diabetic rats. AB - Complications of the gastrointestinal tract in patients with diabetes mellitus can cause marked discomfort and may modify the ability of the patient to maintain normal glucostasis. In an attempt to elucidate some of the factors causing gastrointestinal dysfunction in experimental diabetes we examined the responses of jejunal smooth muscle in streptozotocin-induced diabetes in rats to some of the neurotransmitters and autocoids found in the enteric nervous system. Jejunal tissues from 4- to 5-week diabetic rats were examined for their responses to neurokinin (NK) A, NKB, substance P (SP), bradykinin, neurotensin, bethanechol, isoproterenol and phenylephrine. The affinities for all these agonists, except for SP which increased slightly with diabetes, were the same in both control and diabetic tissues. NKA was the most potent neurokinin and elicited the largest contractile responses from jejunal tissues of both control and diabetic animals. The contractile response to NKA, but not that to NKB or SP, was increased in the jejunum from diabetic animals. Part of this increased responsiveness was antagonized by atropine. The contractile effects of the cholinergic agonist, bethanechol, were not altered by the diabetic state. Decreased relaxation responses in the jejunum from diabetic animals were observed for bradykinin, neurotensin and isoproterenol, but not for phenylephrine. These results suggest that the myogenic actions of several agonists are modified in experimental diabetes. PMID- 2908045 TI - Characterization of the effect of nicotine on vasopressin and atrial natriuretic factor in the rabbit. AB - The effects of nicotine on the secretion of arginine vasopressin (AVP) and of the atrial natriuretic factor (ANF) were examined in conscious rabbits. Nicotine was shown to produce significant increases in plasma AVP from 1.7 +/- 0.4 to 75.3 +/- 35.1 pg/ml (P less than .05) and in plasma ANF levels from 39 +/- 11 to 121 +/- 52 pg/ml (P less than .05) within 5 min of an i.v. dose of 0.5 mg/kg. These nicotine-induced stimulations could not be inhibited by muscarinic (atropine), dopaminergic [(+/-)-sulpiride], alpha (phenoxy-benzamine) or beta adrenergic (propranolol) blockers or by a rapid infusion of fluids. Trimetaphan was ineffective in blocking the stimulation of AVP secretion but completely abolished the nicotine-induced secretion of ANF. The more lipophilic ganglionic blocker, mecamylamine, blocked the stimulation of the secretion of both peptides. The effect of nicotine on AVP production was confirmed in vitro using the rat hypothalamo-neurohypophysial system preparation where nicotine increased AVP secretion in a dose-dependent manner. This in vitro stimulation was blocked by the ganglionic blocker hexamethonium. The increase in ANF plasma concentrations was probably due to a primary response to nicotine, for although exogenous AVP (1 microgram i.v.) increased ANF levels by a factor of 3 (P less than .05), the AVP antagonist [-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid)-2- (O methyl)tyrosine]arginine vasopressin did not prevent the nicotine-induced increase in ANF. Thus, nicotine or its effects appear to stimulate the secretion of ANF and not AVP. It was concluded that nicotine stimulates the secretion of AVP by activating central nicotinic projections to the hypothalamus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2908046 TI - Neurologic deficits and neuronal injury in rats resulting from nonopioid actions of the delta opioid receptor antagonist ICI 174864. AB - The delta opioid receptor antagonist ICI 174864 produces postural abnormalities and barrel rolling after i.c.v. injection and hindlimb and tail flaccidity after spinal subarachnoid injection in rats. These effects appear to result from nonopioid characteristics of ICI 174864 because they are neither shared nor blocked by other opioid antagonists (naloxone, ICI 154129 and WIN 44,441-3) and are produced by two compounds (ICI 174644 and ICI 178173) that are structurally related to ICI 174864 but lack its delta antagonist properties. Barrel rolling and hindlimb paralysis are also produced by dynorphin A-related peptides; however, rats failed to demonstrate tolerance or cross-tolerance to the hindlimb paralytic actions of ICI 174864 or dynorphin A (1-13) after 7 days of continuous spinal intrathecal infusion of either of these compounds. Whereas hindlimb responses to low doses of ICI 174864 (1.6-6.2 nmol intrathecally) were usually transient, higher doses (6.2-25 nmol intrathecally) produced persistent hindlimb motor dysfunction, altered nociception, priapism, hindlimb edema, bladder infarction and atony and urinary incontinence. Neuronal and axonal changes in the lumbosacral spinal cords of rats with persistent and transient neurologic deficits provided direct evidence of the neuropathologic actions of ICI 174864 (3.1 and 6.2 nmol) and ICI 174644 (25 nmol). These results indicate that 1) use of ICI 174864 as a selective delta opioid receptor antagonist is potentially compromised by its nonopioid neuropathologic actions and 2) ICI 174864 and dynorphin A-related peptides are unique among opioid agonists and antagonists in sharing barrel rolling and hindlimb paralytic effects. A similar mechanism of action may underlie the shared nonopioid actions of these peptides. PMID- 2908047 TI - Characterization of a bromoacetylated derivative of pindolol as a high affinity, irreversible beta adrenergic antagonist in cultured cells. AB - We have utilized cultured cell lines to test the utility of N8-(bromoacetyl)-N1 [3-(4-indolyoxy)-2-hydroxypropyl]-(Z)-1,8-diam ino- p-menthane, BIM, a recently synthesized, irreversible beta adrenergic antagonist. Previously available irreversible antagonists of beta adrenergic receptors have generally exhibited low affinity (typical IC50 values greater than or equal to 1 microM). By contrast, S49 lymphoma cells incubated with 10 nM BIM for 120 min and then washed extensively showed a 70% loss in beta adrenergic receptors, as measured by [125I]iodocyanopindolol binding. This loss, which could be prevented by propranolol, represented a decrease in receptor number without a change in affinity of the remaining receptors for [125I]iodocyanopindolol. The BIM-induced decrease in binding sites was persistent in membranes incubated for several hours after BIM treatment. BIM did not inactivate alpha-1 adrenergic receptors on Madin Darby canine kidney cells, alpha-2 adrenergic receptors on human erythroleukemia cells, nor did BIM treatment alter guanyl-5'-yl-imidodiphosphate-mediated regulation of agonist binding to the beta adrenergic receptors in S49 cell membranes. BIM treatment decreased cyclic AMP (cAMP) accumulation in S49 cells in response to the beta adrenergic agonist isoproterenol, but increased prostaglandin E1-stimulated cAMP accumulation (P = .09) without altering cAMP production in response to forskolin. The inactivation of beta receptors in S49 cells by BIM (IC50 = 0.30 nM) correlated closely with the loss in beta adrenergic receptor-mediated cAMP accumulation in these cells (IC50 = 0.59 nM), implying the absence of substantial receptor reserve for this response. We conclude that BIM is a potent, irreversible, selective beta adrenergic antagonist for the study of beta adrenergic receptors in cultured cells. PMID- 2908048 TI - Kinetics of drug action in disease states. XXIV. Pharmacodynamics of diazepam and its active metabolites in rats. AB - The purpose of this investigation was to determine the relative contribution of diazepam and its active metabolites (desmethyldiazepam, oxazepam and temazepam) to the hypnotic activity of this benzodiazepine drug and to assess the role of rate of drug administration as a determinant of the relative concentrations of diazepam and its active metabolites in serum and in the central nervous system at the onset of a predefined pharmacologic endpoint. Rats were given i.v. infusions of diazepam to onset of loss of righting reflex. Samples of cerebrospinal fluid (CSF), blood (for serum) and brain were obtained at that time and were analyzed for diazepam and its active metabolites. Based on the results of six experiments on groups of 6 to 14 rats performed at the same time of day over 11 months, the pharmacologic response of the animals was found to be relatively consistent, with little variation between rats and between experiments in body weight-normalized effective dose and in diazepam serum and CSF concentrations. All three active metabolites of diazepam were found in serum, CSF and brain; they were relatively more prominent in CSF than in serum. Variation of the diazepam infusion rate (four rates between 0.10 and 0.34 mg/min per approximately 200-g rat) was associated with changes in average onset time (50 to 10 min) and dose (26 to 17 mg/kg) required to produce the pharmacologic effect. The drug and metabolite concentrations in CSF determined in these experiments, together with corresponding concentrations obtained by infusion of each active metabolite individually, yielded estimates of their relative hypnotic potency that were unaffected by differences in serum protein binding and tissue distribution.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2908049 TI - Effects of fenoldopam on feline intestinal microcirculation. AB - Experiments were performed to evaluate the effects of the specific dopamine-1 receptor agonist, fenoldopam, on the feline intestinal microcirculation. Cranial mesenteric arterial pressure, cranial mesenteric vein pressure, cranial mesenteric vein blood flow, venous occlusion capillary pressure, pre- and postcapillary resistances, total mesenteric vascular resistance, lymph flow, lymph and plasma protein concentrations, the capillary osmotic reflection coefficient, and the capillary filtration coefficient were determined in an isolated autoperfused jejunal segment in anesthetized fasted cats during intra arterial administration of saline or fenoldopam mesylate in saline. Fenoldopam significantly increased mean cranial mesenteric vein blood flow from 26.8 +/- 3.4 to 33.7 +/- 2.8 ml.min-1.100 g-1. This increase in blood flow was due primarily to a significant decrease in mean intestinal vascular resistance from 3.14 +/- 0.32 to 2.54 +/- 0.2 mm Hg.ml-1.min-1.100 g-1, since cranial mesenteric arterial pressure during fenoldopam infusion was not different from the value obtained during control studies. Mean capillary pressure during fenoldopam infusion (17.2 +/- 0.5 mm Hg) was significantly greater than mean capillary pressure during control studies (15.6 +/- 0.3 mm Hg). The mean lymph flow during fenoldopam infusion (0.186 +/- 0.083 g/dl) was significantly greater than the value obtained during saline infusion (0.08 +/- 0.009 g/dl). Fenoldopam infusion significantly increased the mean capillary filtration coefficient from 0.135 +/- 0.021 to 0.275 +/- 0.035 ml.min-1.100 g-1.mm Hg-1 without altering the capillary osmotic reflection coefficient. These results suggest that specific dopamine-1-receptor stimulation in the small intestine increases the perfused capillary density without altering capillary permeability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2908050 TI - Effects of chronic administration of neuroleptic and anticholinergic agents on densities of D2 dopamine and muscarinic cholinergic receptors in rat striatum. AB - It has been suggested that the development of tardive dyskinesia (TD), a serious and sometimes permanent movement disorder that may follow the use of neuroleptic drugs, is due to an increase in the density of or to a functional supersensitivity of D2 dopamine receptors in the striatum. The atypical neuroleptic clozapine (CLZ) is thought not to cause either acute extrapyramidal syndromes or TD because of its intrinsic anticholinergic activity. This hypothesis was examined using an increase in the density of striatal D2 dopamine receptors after chronic neuroleptic treatment in rats as a model of the changes underlying TD. Rats were treated for 14 days with saline; the neuroleptics CLZ, thioridazine or fluphenazine decanoate (FD); the anticholinergic drugs atropine or trihexyphenidyl or with FD together with atropine or trihexyphenidyl. Specific binding of [3H]spiroperidol to striatal D2 receptors was increased by 26 to 31% (P less than .05) in the groups treated with FD alone or in conjunction with any of the anticholinergic agents. There was no significant increase in the density of D2 receptors after administration of CLZ or thioridazine. The results are consistent with the hypothesis that an increase in the density of D2 receptors is associated with the development of TD. Because coadministration of anticholinergic drugs with FD does not attenuate the effects of the latter drug on striatal D2 receptors, it is likely that other properties of CLZ are responsible for its reduced propensity to produce alterations in D2 receptors and/or TD. PMID- 2908051 TI - [Testicular retention--an unsolved problem]. PMID- 2908052 TI - [The 3d American meeting on hypertension in New York: 24-hour blood pressure determination will be routine in mild hypertension]. PMID- 2908053 TI - [A retrospective study: satisfactory descensus in the majority of boys treated surgically for testicular retention]. PMID- 2908054 TI - [An inquiry study: unexpected low risk of sterility after surgery of testicular retention]. PMID- 2908055 TI - Distribution of DT diaphorase in the rat brain: biochemical and immunohistochemical studies. AB - DT diaphorase [NAD(P)H:quinone oxidoreductase] activity was measured in subcellular fractions from homogenates of striatum, frontal cortex, hippocampus, cerebellum, hypothalamus and substantia nigra. This flavoprotein, which by definition oxidizes dihydronicotinamide adenine dinucleotide and dihydronicotinamide adenine dinucleotide phosphate at equal rates and is completely inhibited by 10(-5) M dicoumarol, was found to constitute 80-90% of the total dihydronicotinamide adenine dinucleotide- and dihydronicotinamide adenine dinucleotide phosphate-reductase activities in all brain regions studied. Antibodies raised against purified cytosolic DT diaphorase from the rat liver cross-reacted with the brain enzyme and inhibited soluble DT diaphorase from striatum and cerebellum to 80-90%. Immunohistochemical studies with the same antibodies demonstrated the occurrence of DT diaphorase immunoreactivity in a population of neurons in the substantia nigra and ventral tegmental area. In some neurons there was a colocalization of DT diaphorase and tyrosine hydroxylase-like immunoreactivity. The dense network of DT diaphorase-immunoreactive fibres in the striatum disappeared along with the dopaminergic innervation after 6 hydroxydopamine lesion. DT diaphorase immunoreactivity was also found in Bergmann glia, astrocytes and tanycytes. No correlation appeared to exist between the localization of neuronal DT diaphorase immunoreactivity and the dihydronicotinamide adenine dinucleotide phosphate-diaphorase-like activity, as defined by tetrazolium salt staining, used as a marker for certain peptidergic and cholinergic neurons. However, in, for example, glial cells in the cerebellum, DT diaphorase might contribute or be responsible for the histochemical dihydronicotinamide adenine dinucleotide phosphate-diaphorase activity. PMID- 2908056 TI - Morphometrical evidence for a complex organization of tyrosine hydroxylase-, enkephalin- and DARPP-32-like immunoreactive patches and their codistribution at three rostrocaudal levels in the rat neostriatum. AB - Tyrosine hydroxylase-like, dopamine- and cyclic AMP-regulated phosphoprotein (Mr = 32,000)-like and enkephalin-like immunoreactive profiles and their codistribution have been evaluated at three rostrocaudal levels of the rat neostriatum by means of a computer-assisted morphometrical method, which allows an objective definition of high density/intensity patches using specific antibodies in combination with the peroxidase-antiperoxidase technique. Our results show that both tyrosine hydroxylase-like, dopamine- and cyclic AMP regulated phosphoprotein-like and enkephalin-like profiles are organized in patches in the rat neostriatum. In the marginal zone, the tyrosine hydroxylase like immunoreactive and dopamine- and cyclic AMP-regulated phosphoprotein-like immunoreactive patches both occupied a large part of the total area. Moreover, in this zone, these putative markers for pre- and postsynaptic elements of dopaminergic synapses also showed a complete spatial overlap. In contrast, the enkephalin-like immunoreactive patches in the marginal zone occupied a smaller area, and showed only an incomplete, albeit significant overlap with the tyrosine hydroxylase-like immunoreactive/dopamine- and cyclic AMP-regulated phosphoprotein like immunoreactive system. In the central zone, tyrosine hydroxylase-like immunoreactive, dopamine- and cyclic AMP-regulated phosphoprotein-like immunoreactive and enkephalin-like immunoreactive patches occupied a much smaller part of the total area than did those in the marginal zone. Within the central zone, enkephalin-like immunoreactive patches occupied a significantly larger area than did the tyrosine hydroxylase-like immunoreactive and dopamine- and cyclic AMP-regulated phosphoprotein-like immunoreactive patches. No consistent pattern of overlap between the three different staining patterns could be seen in the central zone, probably due to the small, inconsistent size of the patches. Trend analysis showed a consistent trend of more tyrosine hydroxylase-like immunoreactive and dopamine- and cyclic AMP-regulated phosphoprotein-like immunoreactive patches in the dorsal than in the ventral striatum, and a trend of more enkephalin-like immunoreactive patches in the rostral than in the caudal striatum. Our data thus demonstrate that, by using computer-assisted morphometrical techniques, it is possible to describe a non-homogenous but overlapping distribution of tyrosine hydroxylase-like immunoreactive and dopamine and cyclic AMP-regulated phosphoprotein-like immunoreactive patches in the rat neostriatum.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2908057 TI - Endopeptidase-24.11 is striosomally ordered in pig brain and, in contrast to aminopeptidase N and peptidyl dipeptidase A ('angiotensin converting enzyme'), is a marker for a set of striatal efferent fibres. AB - Endopeptidase-24.11 (sometimes referred to as 'enkephalinase') is a key cell surface enzyme in the metabolism of neuropeptides. A previous immunohistochemical study mapped the enzyme in pig brain and indicated a striosomal ordering of the enzyme within the striatum. This point has now been confirmed by staining adjacent sections for acetylcholinesterase (by histochemistry) and endopeptidase 24.11 (by an immunoperoxidase method). While there were some general similarities in the mapping of these two hydrolases, e.g. in the caudate-putamen, globus pallidus, olfactory tubercle, substantia nigra and striatonigral tract, there were differences in intensity and in the microscopic distribution, e.g. as in striosomes for which acetylcholinesterase was diminished. Two other membrane peptidases, peptidyl dipeptidase A ('angiotensin converting enzyme') and aminopeptidase N, were also mapped by the same immunohistochemical method. Peptidyl dipeptidase A had some similarities with endopeptidase-24.11, e.g. in its concentration within the striatal nuclei, but clear differences were also apparent, in particular the absence of staining of the former in the globus pallidus and olfactory tubercle. Immunostaining for aminopeptidase N, in contrast to the other peptidases, was observed as a diffuse staining throughout the gray matter. At the microscopic level, two important differences were that staining for aminopeptidase N and peptidyl dipeptidase A was very intense throughout the vasculature of the brain and that striatal efferent bundles of unmyelinated fibres staining positively for endopeptidase-24.11 were depleted of the other two peptidases. All three peptidases were identified in the pia mater. Thus, endopeptidase-24.11, unlike peptidyl dipeptidase A and aminopeptidase N, is a marker for a set of striatal efferent fibres in pig brain. PMID- 2908058 TI - Effects of the unilateral striatal lesion on neurotransmitter markers in the contralateral striatum and both substantia nigrae of the rat. AB - We investigated quantitative changes in possible neurotransmitters and their biosynthetic enzymes in the contralateral striatum and both substantia nigrae following unilateral electrothermic lesions of the striatum in the rat. Two types of changes were observed: (1) the first ones were long-lasting (up to 56 post operative days) effects and consisted in a decrease of GABA content and tyrosine hydroxylase activity in the ipsilateral substantia nigra due to the anterograde and retrograde degeneration of striatal efferent and afferent fibres, respectively, and in a marked increase of glutamate and GABA contents in the contralateral striatum resulting possibly from a modified activity of the collaterals of the glutamatergic corticostriatal fibres and a subsequent secondary increase of GABA. The latter interpretation was supported by the finding that the changes observed were abolished by an additional callosal transection; (2) the second series of changes were transient (only found at 3-7 post-operative days) effects represented by an increase in GABA content, a decrease of tyrosine hydroxylase activity, and a decrease of dopamine content, which mostly appeared in the contralateral substantia nigra. The decrease of dopamine markers may be a subsequent secondary effect of the increase of GABA in the substantia nigra. These results suggest that the contralateral increase of the amino acid transmitters in the striatum and the increase followed by decrease of transmitter markers in the contralateral substantia nigra could be a "plastic" or "compensatory" biochemical response to the unilateral striatal lesions. PMID- 2908059 TI - Effect of psychotropic drugs on identified septohippocampal neurons. AB - The effects of various psychotropic drugs (benzodiazepines, antidepressants, neuroleptics and nootropic drugs, a family of cognition activator agents) on firing rates of septohippocampal neurons, identified by electrical antidromic stimulation, were studied in the medial septum-nucleus of the diagonal band of Broca of rats anaesthetized with urethan. Extracellular potentials from single septohippocampal neurons were recorded using glass pipettes. Drugs were applied by either microiontophoresis or intravenous injections (i.v.). Benzodiazepines produced a marked depression of spontaneous firing rates of septohippocampal neurons whether applied i.v. (diazepam) or iontophoretically (flurazepam, midazolam). In addition, diazepam had a potent depressant effect on the rhythmically bursting activity of the septohippocampal neurons. Baclofen also had an inhibitory effect. Antidepressant drugs (applied by iontophoresis) as well as amphetamine, had a depressant effect on spontaneous firing rates. Neuroleptics (i.v.) had less significant or consistent effects on septohippocampal neurons, although the effects of haloperidol were usually inhibitory. Nootropic drugs were generally ineffective. These data indicate that most psychotropic drugs tested (with the exception of nootropic drugs) have an inhibitory effect on the spontaneous activity of septohippocampal neurons. However, benzodiazepines seem to be more active than antidepressants or neuroleptics. Oxotremorine (i.v.) had a potent excitatory effect on septohippocampal neurons. Atropine (i.v.) increased the septohippocampal neurons' firing rate in some cases. These results are discussed in view of the possible implication of the involvement of septohippocampal neurons in the mediation of the effects of psychotropic drugs on the central nervous system and, more specifically, on the cholinergic systems. PMID- 2908060 TI - Tyrosine hydroxylase-like and dopamine beta-hydroxylase-like immunoreactivity in the gustatory zone of the nucleus of the solitary tract in the hamster: light- and electron-microscopic studies. AB - A quantitative electron-microscopic analysis has been conducted on the neurons within the gustatory zone of the nucleus of the solitary tract of the hamster. The most common group of neurons within the gustatory zone contains both large (X1) and small (X3) members that possess deeply invaginated nuclear profiles. These neurons have somal areas that average 113 micron2 (range 34-281 micron2) and a value of somal area/nuclear area that averages 2.2. Other large and small neurons that have non-invaginated nuclear profiles are also observed. The larger (X2) neurons average 151 micron2 (range 49-487 micron2) and have much cytoplasm and associated membranous organelles that is reflected in a mean value of somal area/nuclear area of 2.6. Members of the X2 group are the largest neurons in the gustatory zone. The smaller (X4) group contains the smallest neurons in the gustatory zone of the nucleus of the solitary tract, averages 50 micron2 (range 16-103 micron2), shows almost no perinuclear cytoplasm and has a mean value of somal area/nuclear area of only 1.5. These findings are consistent with and expand upon the results of similar studies at the light-microscopic level. This grouping has been used to explore the association of tyrosine hydroxylase-like and dopamine beta-hydroxylase-like immunoreactivities with specific populations of neurons that are known to be distributed across the various levels of the gustatory zone. At the light-microscopic level, numerous well-defined and intensely labelled tyrosine hydroxylase-like immunoreactive somata of various morphologies and sizes are observed. Quantification at the electron-microscopic level indicates that 10-15% of the neurons encountered in the dorsal and intermediate levels of the gustatory zone are immunoreactive. The ventral level of the gustatory zone contains few immunoreactive neurons. Tyrosine hydroxylase like immunoreactive neurons possess either non-invaginated or invaginated nuclear profiles and their somal areas average 106 and 142 micron2, respectively. On the bases of size and ultrastructural features, these immunoreactive somata are assigned to the two groups (X1 and X2) of large neurons within the gustatory portion of the nucleus of the solitary tract. In general, small neurons are not immunoreactive. The distribution of dopamine beta-hydroxylase-like immunoreactivity has also been examined in adjacent sections in order to reveal the presence of any putative noradrenergic neurons in the gustatory zone.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2908061 TI - Selective D1 and D2 dopamine agonists produce opposing effects in place conditioning but not in conditioned taste aversion learning. AB - The neurotransmitter, dopamine (DA), has been implicated in place conditioning but the role of D1 and D2 receptors has not been investigated. In Experiment 1, the effects of SKF 38393 (0, 0.01, 0.1, 1.0, 10.0 mg/kg) and quinpirole (0, 0.01, 0.1, 1.0, 2.0, 4.0 mg/kg), preferential D1 and D2 receptor agonists, respectively, were evaluated and compared to (+)-amphetamine (0, 0.01, 0.1, 1.0, 2.0, 4.0 mg/kg). The experiment consisted of three phases. During the preexposure phase, rats explored two distinctive end compartments adjoined by a small tunnel. The time spent in each compartment was recorded. During the 8-day conditioning phase, rats were treated with drug and confined to one compartment for 30 min. On alternate days, rats received saline and were placed in the opposite compartment. Test days occurred over the remaining three days during which drug-free animals explored both compartments. Rats conditioned with (+)-amphetamine demonstrated a dose-dependent increase in time spent in the drug-paired environment from preexposure to test indicating the establishment of a conditioned place preference. Treatment with quinpirole also resulted in a conditioned place preference, however, only an intermediate dose was effective. In contrast, SKF 38393 produced a dose-dependent decrease in time spent on the drug-paired side suggesting the establishment of a place aversion. The idea that D1 receptors may be exclusively involved in mediating the aversive properties of psychomotor stimulants was tested in Experiment 2 employing a conditioned taste aversion paradigm. The results did not support this notion; it was found that both quinpirole and SKF 38393 produced a conditioned taste aversion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2908062 TI - Naloxone, but not Tyr-MIF-1, reduces volitional ethanol drinking in rats: correlation with degree of spontaneous preference. AB - The possible relationship between the actions of ethanol and opiates led us to examine the effect of opiate antagonists on ethanol intake in rats with a free choice of water. Naloxone (NAL) significantly reduced intake of ethanol. This effect was much greater in "high-preferring" (ethanol/total fluid intake greater than 60%) than in "low-preferring" (ethanol/total fluid intake less than 30%) rats. Furthermore, a correlation was found between the degree of spontaneous preference (ethanol/total fluid intake ratio) and the reduction of ethanol drinking by NAL. Sensitivity to NAL increased with increased preference for ethanol. Neither Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) nor MIF-1 (Pro-Leu-Gly-NH2) caused a significant modification of ethanol intake. This study shows that NAL can reduce volitional ethanol intake in rats and provides further evidence that Tyr-MIF-1 does not always act like NAL. PMID- 2908063 TI - Combined opiate/adrenergic receptor blockade enhances squirrel monkey vocalization. AB - This study provides evidence for the interaction between opiate and noradrenergic neuronal systems on primate vocal behavior. The rate of twitters produced by adult squirrel monkeys was increased in an additive or synergistic manner by the combined administration of the alpha 2 adrenergic antagonist yohimbine and the opiate antagonist naloxone. Similar effects were not demonstrated on the isolation call. In addition, the drug combination led to an increase of autonomic symptoms. The anatomical localization of these findings and mechanism for the production of increased twitters requires further investigation. PMID- 2908064 TI - Advantages and disadvantages of a rapid method to train drug discrimination. AB - In an effort to reduce the often extensive period of time needed to train rats to discriminate between a drugged and nondrugged state, a fast training regimen was employed with 1.5 mg/kg 3,4-methylenedioxymethamphetamine (MDMA) used as the training drug in ten rats. This protocol consisted of one to three training sessions per day and it was compared to the more conventional method of once-per day training in an equal number of rats. Results indicate that the fast-trained rats learned the discrimination in significantly fewer sessions than the slowly trained rats. However, the subsequent dose-response experiments indicate that when the fast-trained rats are tested with various doses of MDMA, without prior vehicle treatment, their sensitivity to the drug is less than that of the slowly trained rats. When a vehicle session is presented prior to drug dose-response testing, both groups perform similarly. It appears that the preceding vehicle sessions function as a reference point for the fast-trained rats and, although the more rapid training regimen allows for faster learning, these treatment regimens should be employed with caution when subsequent dose-response tests and generalization tests with other drugs are conducted. PMID- 2908065 TI - Antihistaminic drugs increase feeding, while histidine suppresses feeding in rats. AB - The present studies tested the hypothesis that histamine blockade stimulates appetite, while increases in histamine levels suppress appetite. Results show that the classical antihistamines cyproheptadine and promethazine both produced significant and long-lasting increases in food intake. Pronounced appetite stimulation was also seen following the administration of doxepin, the most potent antihistamine among the antidepressants. In contrast, administration of the histamine precursor histidine produced a profound suppression in food intake. The results thus suggest that an inverse relationship may exist between histamine and food intake. PMID- 2908067 TI - Serotonergic-dopaminergic mediation of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy"). AB - A series of three experiments were conducted to investigate the possible serotonergic and dopaminergic mediation of the discriminative stimulus properties of the "designer" drug MDMA. In Experiment 1, rats trained to discriminate 1.5 mg/kg (+/-)-MDMA from its vehicle at 20 min postadministration were shown to generalize to another drug of abuse, N-ethyl-3,4-methylenedioxyamphetamine (MDE) and to the serotonergically-active agents norfenfluramine and TFMPP. In contrast, testing of various dopaminergically-active agonists did not result in MDMA-like responding. In Experiment 2, dopaminergic and serotonergic antagonist were employed to observe their effect upon MDMA discrimination at 20 min postinjection. The serotonin antagonist pirenperone significantly decreased MDMA discrimination, whereas the dopamine decreasing drugs CGS 10746B and haloperidol had no effect. In Experiment 3, another group of rats were trained to discriminate MDMA at 105 min postadministration to investigate if, at this (later) time, the dopaminergic properties of MDMA may be more salient. Indeed, the dopaminergically-active drugs had a heightened effect upon MDMA at this later time, although the serotonergic component of the MDMA discriminative stimulus was predominant. The results suggest that the effects of MDMA at 20 min postadministration are solely serotonergic in nature. At 105 min postinjection there appears to be the presence of a weak dopaminergic component. This biphasic serotonergic-then-dopaminergic action of MDMA may explain the reported human experience with the drug, as well as the often controversial results in the literature. PMID- 2908066 TI - Alpha noradrenergic agonists promote catalepsy in the mouse. AB - Alpha adrenergic receptors are important in motor control. Adrenergic drugs reportedly modulate the catalepsy caused by other agents, such as opiates and neuroleptics. We tested a variety of adrenergic agonists and blockers in a nondrug, mouse model of catalepsy. A major cataleptic effect was produced by both alpha agonists, phenylephrine (0.5 to 3 mg/kg, IP) and clonidine (0.5 to 2 mg/kg), and this catalepsy was antagonized by pretreatment with both of the respective antagonists, phenoxybenzamine (alpha-1) and yohimbine (alpha-2) (p less than 0.0001). The mixed beta agonist, isoproterenol (2 mg/kg), appeared to have a minor cataleptic effect, and this was abolished by beta antagonist. Open field locomotor scores during the same treatments revealed that catalepsy and hypokinesia are dissociable. PMID- 2908068 TI - Antiamnesic effects of D-pipecolic acid and analogues of Pro-Leu-Gly-NH2 in rats. AB - The antiamnesic effects of prolyl-leucyl-glycinamide (PLG) and analogues of this tripeptide were investigated in rats. Retrograde amnesia was induced by electroconvulsive shock treatment and the degree of amnesia was characterized by the attenuation of one-trial learning passive avoidance response. PLG resulted in dose-dependent attenuation of retrograde amnesia. Structural modifications included N-terminal protection, substitution of the C-terminal NH2 group, replacement of the N-terminal amino acid, and replacement of the second amino acid of the tripeptide. Some tripeptides, all of them containing D-pipecolic acid instead of the N-terminal proline, were more effective than PLG. Therefore, D pipecolic acid, D-pipecolamide and their N-terminally protected analogues were also investigated, and were found to have powerful antiamnesic effects. PMID- 2908069 TI - Neuroleptic-induced reduction of quipazine-elicited head-twitches in rats: possible involvement of striatal dopaminergic supersensitivity. AB - Rats were treated with a single large dose of various neuroleptic compounds and, 5-7 days after, they were assayed for either behavioral sensitivity to apomorphine (hypermotility and stereotyped behavior) or head-twitch response to the mixed serotonin-dopamine agonist quipazine. The animals withdrawn from chlorpromazine, fluphenazine, haloperidol, metoclopramide and the D1 selective blocker SCH 23390, showed enhanced hypermotility and/or stereotyped responses to apomorphine and reduced head-twitch response to quipazine. The rats withdrawn from thioridazine, (-)-sulpiride and sultopride responded to apomorphine only with enhanced hypermotility while their response to quipazine was either unchanged or even increased. The results are discussed in terms of dopaminergic brain areas and/or receptor subtypes involved in the modulation of the head twitch response to quipazine. We concluded that an enhancement of dopaminergic tone at the striatal level could be related to the reduced head-twitch response to quipazine. PMID- 2908070 TI - Differential effects of neuroleptic drugs on the delayed matching-to-sample performance of pigeons. AB - The effects of clozapine, thiothixene, sulpiride, chlorpromazine and loxapine were examined in pigeons responding under a delayed matching-to-sample (DMTS) procedure using 0-, 2- and 8-sec delay intervals. Chlorpromazine (3-100 mg/kg), thiothixene (0.03-1.7 mg/kg), clozapine (0.1-5.6 mg/kg) and loxapine (0.1-10 mg/kg) produced dose-related decreases in the percent of correct responses (accuracy). With the exception of chlorpromazine, the relative magnitude of the accuracy-decreasing effects were unrelated to the length of the delay interval and the nondrug levels of accuracy. In contrast to these accuracy-decreasing effects, sulpiride (3-300 mg/kg) failed to decrease accuracy across the range of doses evaluated. Chlorpromazine, loxapine and clozapine increased response rates at low doses and then decreased response rates as the dose was increased. Thiothixene and sulpiride only decreased response rates in a dose-dependent fashion. The order of potency for the rate-suppressing effects of these drugs was thiothixene greater than clozapine = loxapine greater than chlorpromazine greater than sulpiride. The results of the present investigation suggest that, despite similar dopamine antagonist properties, neuroleptics produce qualitatively different effects in pigeons responding under DMTS procedures. PMID- 2908071 TI - [Fractures of the maxilla with involvement of the orbital floor. 1. Introduction]. PMID- 2908072 TI - [Tolerance for nitrates]. PMID- 2908073 TI - [Current developments in the treatment of unstable angina pectoris and acute myocardial infarct]. PMID- 2908074 TI - [Cardiac stimulation in the treatment of tachyarrhythmias]. PMID- 2908075 TI - [The therapeutic aspects in atrial fibrillation with a rapid rhythm]. PMID- 2908076 TI - [Molecular mechanism of tolerance for vasodilator nitrates]. PMID- 2908077 TI - [Early postinfarct angina--its incidence, significance, prognosis]. PMID- 2908078 TI - [Phonomechanocardiographic aspects during effort in patients with angina pectoris]. PMID- 2908079 TI - [Mechanisms of the membrane transport of sodium and potassium in arterial hypertension (the pathogenetic and clinical considerations)]. PMID- 2908080 TI - [Alcoholic cardiomyopathy--an etiological factor in heart failure-generating cardiomegaly]. PMID- 2908081 TI - [The proarrhythmia effects of anti-arrhythmia drugs]. PMID- 2908083 TI - [Symposium on nursing--a fertile forum for nurses. Interview by Mette-Marie Davidsen]. PMID- 2908082 TI - [Catalog of the entomologic collections of the Faculty of Public Health of the University of Sao Paulo--(2d Serie II)--Culicidae]. PMID- 2908084 TI - [Granulocytopenia in treatment with salazopyrin]. PMID- 2908085 TI - A decade of photorespiratory nitrogen cycling. PMID- 2908086 TI - snRNP mediators of 3' end processing: functional fossils? PMID- 2908087 TI - Reversible phosphorylation of an enhancer binding protein regulates the transcription of bacterial nitrogen utilization genes. PMID- 2908088 TI - [Status of antihistaminics in the therapy of bronchial asthma]. AB - Effects of histamine on bronchial mucosal permeability, mucus secretion and smooth muscle cells change the airway geometry to bronchoconstriction. Histamine is also involved in the underlying early and late asthmatic response, chronic inflammation and increased airway responsiveness. The actions of histamine enhancing bronchial obstruction arise from its interaction with specific H1 receptors. In contrast to the bronchoconstrictive potency of histamine, antagonists do not lower bronchial resistance. Therefore they are without any therapeutic effect in acute asthmatic attacks. However, histamine H1-antagonists produce significant protection against bronchospasms which are induced experimentally by a variety of conditions in asthmatic patients. The protective actions of modern histamine H1-antagonists are caused mainly by the capacity to inhibit synthesis or release of mediators which are implicated in airway inflammation and hyperresponsiveness. Anti-inflammatory properties and restoration of desensitize beta-adrenoceptor responsiveness account for the possibility to reduce treatment with glucocorticoids and other drugs at least in some cases. In summary, modern H1-antagonists are useful in longterm control of moderate forms of primarily allergic asthma. PMID- 2908089 TI - [Experimental studies with external and internal administration of antihistaminics in insect venom allergies]. PMID- 2908090 TI - [Chronic urticaria--still a vexing problem? Progress in diagnosis and therapy]. AB - Despite the suggestion than an intolerance reaction could be a possible cause of chronic urticaria in some cases, the pathogenesis of this disease remains enigmatic. It is unlikely that an intolerance reaction to substances used in provocation testing is the cause of the daily rashes. It rather seems that the intolerance reaction is an indication of a certain instability of the mast cell membrane of other factors of the reaction cascade leading to the wheals. Fortunately, an effective symptomatic therapy is available in such cases where the cause cannot be detected and the trigger cannot be avoided. The modern, non sedating H1-antihistamines have been tested in clinical-experimental studies as well as in a multicentric study in patients with chronic urticaria. In histamine induced wheals, terfenadine was slightly superior to other non-sedating H1 blockers, when the grade of reduction of wheals and flare areas was taken as criterion. In clinical studies, another antihistamine, loratadine, was slightly, but statistically not significantly superior to terfenadine. In cases that cannot be effectively treated with H1-blockers alone, the additional administration of non-steroidal antiphlogistics (acetylsalicylic acid, indomethacin) is recommended. To avoid aggravation of the symptoms caused by the antiphlogistics, the drugs must be given in increasing dosages and after concurrent treatment with H1-blockers. With this combined therapy, about 50% of the patients present amelioration. PMID- 2908091 TI - [Adverse effects of antihistaminics]. AB - Of most antihistamines more or less pronounced sedative effects are known. In recently developed substances this effect is said to be less or absent. After some days of application the sedative effect may decrease, but it can be enhanced by simultaneous intake of psychotropic drugs, sedatives or alcohol. There are important interindividual differences. The Drug Commission of the German Medical Profession (AKdA) received reports concerning tiredness, somnolence (even with new antihistamines), CNS-stimulation, nervousness, insomnia and paroniria have also been observed. Furthermore cases of dyskinesia have been reported, which are already described in the literature after long term intake, as well as anticholinergic reactions. Despite of their use as antiallergic drugs, reports on hypersensitivity reactions due to antihistamines, up to anaphylactic reaction have been not infrequently received by the AKdA. In rare cases disturbances of blood cell formation have been reported besides observations of gastrointestinal disorders, increase of appetite and weight. Abuse of antihistamine containing drugs was reported mainly for combinations with psychotropic agents. PMID- 2908092 TI - Effectiveness and safety of captopril (Tensiomin) in patients with hypertension. AB - Twenty patients with moderate (4) to severe (16) hypertension, whose blood pressure (BP) could not be controlled on the previous combined antihypertensive therapy, were investigated. In acute studies the first doses of captopril, 25 and 50 mg led to a significant drop in BP 30 min after administration. The maximum fall in BP was recorded at 90-120 min and this effect was maintained throughout the whole observation period (8 hours). The fall in BP was similar in supine and standing positions and there was no change in the heart rate. During long-term (14.5 months) therapy only 2 out of the 20 patients exhibited continuing good BP control with captopril monotherapy of a maximum daily dose of 150 mg. A comparison of the acute and chronic BP lowering effects of captopril showed that the first dose of captopril caused a significantly greater decrease in BP than chronic monotherapy. However, combined captopril with a diuretic or with a diuretic and calcium antagonist or beta blocker provided a sustained BP control, significantly better than the previously used anti-hypertensive combinations (182 +/- 27/115 +/- 11 mmHg vs 164 +/- 20/104 +/- 11 mmHg p less than 0.05). The Hungarian captopril preparation (Tensiomin), similarly to other captopril products, through its angiotensin converting enzyme inhibition, caused an increase in plasma renin activity and in concentration of plasma angiotensin I and a decrease in plasma angiotensin II. Eight out of the 20 patients developed side effects, which disappeared spontaneously in 4 patients within 2-14 days. Captopril was withdrawn in 3 patients for not achieving satisfactory BP control and/or because of side effects. It is concluded that captopril is safe and effective in the long-term treatment of hypertension, however, majority of the patients with severe forms of hypertension required double or multiple combinations. PMID- 2908093 TI - [Survey of anxiolytic premedication in dentistry]. PMID- 2908094 TI - Use of microdilution to assess in vitro antiamoebic activities of Brucea javanica fruits, Simarouba amara stem, and a number of quassinoids. AB - A microdilution technique for the assessment of in vitro activity against Entamoeba histolytica was devised and validated with metronidazole. The test was used to detect the antiamoebic activities of plant extracts prepared from the traditional remedies Brucea javanica fruits and Simarouba amara stems. The activity was associated with quassinoid-containing fractions. The 50% inhibitory concentrations for some quassinoids against amoebae were determined by using the microdilution method. These concentrations ranged from 0.019 micrograms.ml-1 for bruceantin, the most active quassinoid, to greater than 5 micrograms.ml-1 for glaucarubol, the least active compound tested. These results are discussed with reference to the known activities of these compounds against Plasmodium falciparum. Overall, the activities of the quassinoids against both protozoa are similar. The microdilution technique will be useful in the search for novel antiamoebic drugs. PMID- 2908095 TI - Human brain D1 and D2 dopamine receptors in schizophrenia, Alzheimer's, Parkinson's, and Huntington's diseases. AB - Because dopamine D2 receptors are known to be elevated in schizophrenic brain striata, this study examined whether a similar dopamine receptor elevation occurred in other diseases including neuroleptic-treated Alzheimer's and Huntington's diseases. The average D1 density in postmortem striata from Alzheimer's patients was 17.6 +/- 0.1 pmol/g, similar to an age-matched control density of 16.6 +/- 0.4 pmol/g. The average D1 density in schizophrenia patients was 19.0 +/- 0.6 pmol/g, similar to the age-matched control density of 17.9 +/- 0.6 pmol/g. In Parkinson's disease patients, however, the D1 receptor density was elevated, with values of 22.8 +/- 1.2 pmol/g (in patients not receiving L-DOPA) and 19.6 +/- 1.5 pmol/g (in patients receiving L-DOPA) compared to the age matched control density of 16.0 +/- 0.4 pmol/g. The D2 receptors in Alzheimer's striata averaged 13.4 +/- 0.6 pmol/g (in patients who had not received neuroleptics), almost identical to the control density of 12.7 +/- 0.3 pmol/g. The average D2 density in neuroleptic-treated Alzheimer's striata was 16.7 +/- 0.7 pmol/g, an elevation of 31%, the individual values of which had a normal distribution. In Parkinson's disease patients, the D2 densities were elevated in tissues from patients not receiving L-DOPA (19.9 +/- 1.5 pmol/g in putamen and 14.8 +/- 1.2 pmol/g in striatum) compared to the age-matched control values of 13.0 +/- 0.4 pmol/g and 12.6 +/- 0.3 pmol/g, respectively. In Huntington's disease patients, the D2 density averaged 7.5 +/- 0.4 pmol/g in patients who had not received neuroleptics, but was 10.3 +/- 0.6 pmol/g in those who had. Although all of the D1 and D2 densities in each of the above diseases and subgroups revealed a normal distribution pattern, the D2 densities in schizophrenia displayed a bimodal distribution pattern, with 48 striata having a mode at 14 pmol/g, and the other 44 striata having a mode at 26 pmol/g. Thus, compared to the neuroleptic-induced and unimodal elevations in D2 of 31% in Alzheimer's disease and 37% in Huntington's disease, the schizophrenic striata with a mode of 26 pmol/g (105% above control) appear to contain more D2 receptors than can be accounted for by the neuroleptic administration alone. PMID- 2908096 TI - Report on schizophrenia of the American College of Neuropsychopharmacology. The Ad Hoc Committee on Schizophrenia. PMID- 2908097 TI - Discrepancies in serological tissue typing revealed by DNA techniques. AB - DNA techniques were applied to typing a population of renal patients in order to assess the number of discrepancies between this technique and the serological technique. Five patients had been given an incorrect type by serology, and in 22 instances allogenotypes were found where previously there had been a serological blank. DNA typing was also able to determine allogenotypic subtypes that correlated with DR antigens difficult to split by serology and to determine allogenotypic subtypes correlating with DR antigens not known to have a split by serology. Whereas DNA typing provided a result first time of testing on all but 3 patients, the average number of serological testings for each patient was 1.9. PMID- 2908098 TI - Mononuclear cells infiltrating kidney allografts in the absence of rejection. Effect of conversion from cyclosporin to azathioprine therapy. AB - Focal small mononuclear cell infiltrates were found in renal allograft biopsies of 13/14 transplant recipients with a stable function after long-term cyclosporin A (CsA) therapy. Phenotypical analysis of the infiltrating cells using monoclonal antibodies showed a slight preponderance of T cells (56% +/- 8%), with only small percentages of B cells (5% +/- 2%), NK cells (2% +/- 1%), and monocytes (2% +/- 1%). Within the T-cell population the median calculated CD4/CD8 ratio was 1:3. Thirty-five percent of the infiltrating mononuclear cells remained unidentified with the monoclonal antibody panel used (silent cells). Three months after immunosuppressive therapy had been changed from CsA to azathioprine (AZA), the size of the infiltrates was significantly increased and there was a marked invasion of mononuclear cells between tubular epithelium despite a significant improvement in creatinine clearance (P less than 0.01). the phenotypical composition of these infiltrates was dominated by T cells (84% +/- 3%), with a median CD4/CD8 ratio of 2:7 due to an increase in CD4+ cells and a decrease in CD8+ after conversion (P less than 0.05). The percentages of B cells, NK cells, and monocytes showed no significant changes after conversion. During AZA therapy nearly all infiltrating mononuclear cells were stained with the monoclonals used, leaving no silent cells postconversion. PMID- 2908099 TI - Intellectual impairment in Parkinson's disease: clinical, pathologic, and biochemical correlates. AB - The prevalence of overt dementia in 27 studies representing 4,336 Parkinson's disease (PD) patients was 39.9%. The studies reporting the highest incidence of intellectual impairment (69.9%) used psychologic assessment techniques, whereas studies identifying the lowest prevalence of dementia (30.2%) depended on nonstandardized clinical examinations. Neuropsychologic investigations reveal that PD patients manifest impairment in memory, visuospatial skills, and set aptitude. Language function is largely spared. Intellectual deterioration in PD correlates with age, akinesia, duration, and treatment status. Neuropathologic and neurochemical observations demonstrate that PD is a heterogeneous disorder: the classic subcortical pathology with dopamine deficiency may be complicated by atrophy of nucleus basalis and superimposed cortical cholinergic deficits, and a few patients have the histopathologic hallmarks of Alzheimer's disease. Mild intellectual loss occurs with the classic pathology, and the more severe dementia syndromes have cholinergic alterations or Alzheimer's disease. Thus, PD includes several syndromes of intellectual impairment with variable pathologic and neurochemical correlates. PMID- 2908100 TI - The neurologic implications of depression in the elderly. PMID- 2908101 TI - [Studies on surface electricity of Entamoeba histolytica]. PMID- 2908102 TI - Long-lasting lowering of serum growth hormone and prolactin levels by single and repetitive cabergoline administration in dopamine-responsive acromegalic patients. AB - Cabergoline, the new long-acting dopaminergic ergoline derivative, was given orally in single doses of 0.3 and 0.6 mg to eight dopamine-responsive acromegalic patients. Serum GH and PRL levels were determined before treatment, 3, 4, and 6 h and 1, 3, 5, 7 and 14 days after treatment. A control test with a single oral dose of 2.5 mg of bromocriptine was also performed. Cabergoline induced a marked fall in serum PRL level, starting within 3 h and continuing for 7 days after administering 0.3 mg, and for 14 days after 0.6 mg. The mean maximal decrease was 49% after 0.3 mg and 63% after 0.6 mg and occurred after 24 h in both cases. The latter was of similar magnitude to that induced by bromocriptine (67% at 4 h). Serum GH levels did not change after 0.3 mg of cabergoline, but decreased significantly from 3 h to 3 days after 0.6 mg of the compound with a mean maximal decrease of 42% after 24 h, and from 3 to 6 h after giving bromocriptine (mean maximal decrease 63% at 4 h). Once a week repeated administration of 0.3-0.6 mg of cabergoline was carried out in six patients, five of whom had completed the acute study; a normalization of serum GH and insulin-like growth factor I (IGF-I) levels occurred in three patients, one of whom had very high pretreatment values. In three poorly or nonresponsive patients, a better response, as assessed by both GH and IGF-I levels, was induced by increasing the dose up to 0.6 mg twice or 0.4 mg three times a week; in one case this was associated with marked tumour shrinkage. Sustained normalization of PRL levels was achieved in all cases. These data indicate that a single dose of 0.6 mg of cabergoline inhibits GH as well as PRL secretion in dopamine-responsive acromegalic patients and suggests that doses of 0.3-0.6 mg once to three times a week may prove suitable for treatment of this condition. PMID- 2908103 TI - The effect of calcitonin on growth hormone secretion in man. AB - To determine whether human calcitonin inhibits GH secretion in man, as has been described for salmon calcitonin, the effect of an i.v. bolus of human calcitonin or saline on GH release after either insulin-induced hypoglycaemia or the administration of GH-releasing hormone (GHRH) or saline was studied. After the injection of calcitonin, no spontaneous GH surges were seen; the GH response to hypoglycaemia was diminished and the response to GHRH almost completely suppressed. Administration of calcitonin also caused a small and transient rise in plasma PRL and TSH but not LH levels, and no change in the integrated PRL or TSH response. Calcium and magnesium levels did not change. It is concluded that human calcitonin suppresses GH secretion in man, but not by suppressing GHRH and probably not by increasing somatostatin release. In addition, calcitonin has limited PRL and TSH-releasing activity. PMID- 2908104 TI - HLA class II DNA genotypes in Graves' disease: clues to inheritance of the HLA linked component of susceptibility. AB - Restriction fragment length polymorphism analysis using DQ alpha, DQ beta and DR beta cDNA probes was performed in Graves' disease patients and control subjects. The following restriction fragment patterns were increased in frequency in patients compared with control subjects: 10 + 7.0 + 4.0kb DR beta/TaqI fragments (66% vs 32%; P less than 0.01; corrected P less than 0.06), 7.0 + 4.0kb DQ beta/BamHI fragments (55% vs 15%; P less than 0.001; corrected P less than 0.006), and a DQ alpha/TaqI 4.6kb fragment (75% vs 36%; P less than 0.005; corrected P less than 0.02). These associations could be accounted for by the known association of the B8-DR3 haplotype with the disorder. No non-DR3-related restriction fragment pattern was associated with the disease using any of the probes with restriction enzymes TaqI and BamHI. The 10 + 7.0 + 4.0kb DR beta/TaqI restriction pattern was identified in 23 of 35 Graves' disease patients. All 23 subjects were heterozygous for this pattern. This was inconsistent with simple recessive inheritance of the DR3-associated component of disease susceptibility (P = 0.01). The implications of these findings are discussed with reference to models for the inheritance of the HLA-linked component of Graves' disease susceptibility. PMID- 2908105 TI - Desensitization of guanylate cyclase in nitrate tolerance does not impair endothelium-dependent responses. AB - Tolerance of vascular smooth muscle to nitroglycerin could be induced by an impaired biotransformation of nitroglycerin to nitric oxide, the activator of soluble guanylate cyclase, or by desensitization of guanylate cyclase to activation with nitric oxide. The latter would imply that there would also be tolerance to nitric oxide delivered from sodium nitroprusside or endothelial cells. Therefore, endothelium-denuded segments of rabbit aorta were treated with nitroglycerin to induce tolerance, and were then assessed for mechanical response, cyclic GMP content, and activity of soluble guanylate cyclase after addition of nitrovasodilators. Nitrate tolerance decreased the vasodilation and the increase in cyclic GMP elicited by nitroglycerin, but not that elicited by sodium nitroprusside or endothelium-derived relaxing factor, in norepinephrine contracted segments. However, soluble guanylate cyclase in the supernatants of homogenates of nitrate-tolerant aortas was desensitized to activation with nitroglycerin and sodium nitroprusside. As the guanylate cyclase was still responsive to activation by nitric oxide in the intact, tolerant smooth muscle, an impaired biotransformation of nitroglycerin rather than desensitization of soluble guanylate cyclase may be the mechanism by which nitrate tolerance develops. PMID- 2908106 TI - Clorazepate, correlation between metabolism and anticonvulsant activity. AB - The metabolism and the anticonvulsant effect of clorazepate were followed for 2 h after its i.v. administration to mice. The ED50 of the drug was 12 mg/kg at 1 min against pentetrazole-induced convulsions (45 mg/kg i.v.), it reached a minimum at 1 h (2.0 mg/kg) and rose to 2.7 mg/kg at 2 h. The concentrations of unchanged clorazepate and its metabolites, desmethyldiazepam and oxazepam, were determined in plasma and brain after administration of the respective ED50s. Unchanged clorazepate could be detected in plasma for the first hour but never in brain, so it can be considered as inactive pro-drug. The brain concentrations of desmethyldiazepam and oxazepam after the respective ED50s of clorazepate were considerably higher at 1 and 15 min than after longer time intervals. This may be explained by a time lag needed to reach and bind to the benzodiazepine receptor. PMID- 2908107 TI - [10-month follow-up of 181 anti-HIV positive patients]. PMID- 2908108 TI - [Beta-blocker therapy in heart failure: rational basis, indications, dosages and cautions]. PMID- 2908109 TI - Single dose pharmacokinetics of cetirizine in young and elderly volunteers. AB - The pharmacokinetics of the H1-receptor antagonist cetirizine were studied from 0 to 48 h after a single oral intake of 10 mg in 10 elderly volunteers (60 to 90 years) and in 10 young healthy volunteers (21 to 29 years). In young healthy volunteers about 60% of an oral dose of cetirizine was excreted in the urine in unchanged form. Mean plasma concentrations were slightly higher in the elderly subjects. Cmax (362 ng/ml), Tmax (1.30 h), terminal half-life (11.8 h) and AUC infinity (4316 ng.h/ml) in the elderly subjects were somewhat higher than in the young subjects (Cmax: 337 ng/ml, Tmax: 1.12 h, terminal half-life: 10.6 h, AUC: 3721 ng.h/ml), but the difference was not significant. The mean cumulative urinary excretion at 32 h was significantly lower in the elderly subjects. It is concluded that the slight differences in pharmacokinetics of cetirizine between young and elderly subjects after single oral intake can be attributed to the decreased renal clearance in the elderly. PMID- 2908110 TI - Modification of hypothalamic content of growth hormone regulatory peptides in maternally deprived neonatal rats. AB - The possibility that maternal deprivation (MD) modifies growth hormone releasing hormone (GHRH) and/or growth hormone release inhibiting hormone (GHRIH) in 10-day old rat pups was investigated by quantifying the total hypothalamic content of these two hormones which regulate the release of growth hormone (GH), since MD has previously been shown to suppress circulating GH levels. At 10 days of age, rat pups were maternally deprived for either 1 or 6 hours (control pups remained with their mother while littermates were deprived). At the end of the time period, hypothalami were dissected free, homogenized, frozen, and then lyophilized. Reconstituted extracts were later subjected to radioimmunoassay for GHRH and GHRIH. Tests for differences in the brain content of the hormones were performed by analysis of variance; multiple comparison of the means was performed using Tukey's test. A significant increase in the GHRIH content was observed in the hypothalami of maternally deprived rats as compared to control animals (P = 0.026). Small differences in the mean GHRIH content between the different experimental groups suggested a trend toward elevation of GHRIH after either 1 or 6 hours of MD and a trend toward higher levels in males as compared to females (P = 0.0636). No differences in hypothalamic GHRH content were found between maternally deprived and control pups (175.8 pg/hypothalamus vs. 171.5 pg/hypothalamus). The modification of GHRIH hypothalamic content during MD of neonatal rats demonstrated in the present study may be related to the suppression of GH that is known to result from MD. PMID- 2908111 TI - Antenatal diagnosis of the hemoglobinopathies. PMID- 2908112 TI - Rilmenidine (S 3341) and the sympathoadrenal system: adrenoreceptors, plasma and adrenal catecholamines in dogs. AB - 1. The effects of rilmenidine, a new alpha 2-adrenoreceptor agonist with antihypertensive properties, were investigated on plasma catecholamines, blood cell adrenoreceptors and adrenal medullary function. 2. In conscious sino-aortic denervated (SAD) dogs, rilmenidine (1 mg kg-1 orally for 2 weeks) significantly reduced both blood pressure and heart rate when compared with placebo treatment. The drug decreased plasma noradrenaline and adrenaline levels and corrected the decrease in leucocyte beta-adrenoreceptors observed in placebo-treated SAD dogs. There was no change in platelet alpha 2-adrenoreceptors. 3. In anaesthetized normotensive dogs, rilmenidine (0.1 and 0.3 mg kg-1 i.v.) induced a dose dependent decrease in both cardiovascular parameters (blood pressure and heart rate) and catecholamine release from the adrenal medulla. 4. The present study shows that rilmenidine decreases sympathetic tone mainly by an action on the adrenal medulla. In addition, its ability to lower blood pressure in SAD dogs, i.e. a model of hypertension in which high sympathetic tone is present, indicates that rilmenidine may also depress other parts of the sympathetic nervous system. PMID- 2908113 TI - No evidence for more than one type of alpha 1-adrenoreceptor in rabbit pulmonary artery. AB - 1. The effects of the alpha-adrenoreceptor antagonists, prazosin and yohimbine, have been examined on the isometric contraction of the rabbit pulmonary artery produced by alpha 1-adrenoreceptor agonists. Cocaine, corticosterone and propranolol were present throughout and either a single or two concentration response curve method was used. 2. Prazosin and yohimbine competitively antagonized the responses to agonists but did not reveal differences between agonists. 3. Using the single concentration-response curve method, prazosin had pA2 values of 9.06 against clonidine and 8.76 against methoxamine. 4. Using the two concentration-response curve method the absolute pA2 values of prazosin (8.65 against phenylephrine, 8.78 against clonidine) and yohimbine (5.73 against phenylephrine, 5.72 against clonidine), as well as the relative potencies of the two antagonists (prazosin approximately 1000 times more potent than yohimbine), suggest that both agonists act on alpha 1-adrenoreceptors. 5. There is no evidence from this study to support the suggestion that the rabbit pulmonary artery contains two subtypes of alpha 1-adrenoreceptor. PMID- 2908115 TI - Macromolecular dynamics of the cell surface during the formation of coated pits is revealed by fracture-flip. AB - We report here the macromolecular dynamics of the cell surface of rat alveolar macrophages during spreading on a substratum, a process that involves the formation of numerous coated pits. We used 'fracture-flip' to prepare high resolution platinum-shadowed replicas of membrane surfaces. Our observations show the following sequence of events associated with coated pit formation: at 4 degree C the cell surface of macrophages is covered with a moderate density of particulate components, with most ranging from 10 to 25 nm in diameter. These particles appear to be randomly distributed over the cell surface. Incubation of adherent cells at 37 degree C for 15 min results in the formation of large loose clusters (area 0.5-4 micron2) of particles on the adherent surfaces. After incubation of macrophages for 30 min at 37 degree C, these clusters become tighter and eventually form circular depressions (200-300 nm in diameter), which we interpret as part of a process of invagination. After 60 min, the depressions become much steeper. At this time surface particles can be observed on the intervening non-invaginated regions, and the peripheral region of the adherent membrane, as well as the free membrane. Fracture-flip reveals the presence of structures undetected in previous electron-microscopic studies and provides ultrastructural evidence for the clustering of surface macromolecules that is involved in the formation of coated pits. PMID- 2908114 TI - Prostaglandin I2 and thromboxane A2 production in relation to alpha 1 and alpha 2 adrenoreceptor activation in the normotensive and hypertensive rat. AB - 1. The perfused mesenteric arterial bed (MAB) from normotensive (WKY) and hypertensive (SHR) rats was used as a model to investigate the relationship between alpha 1 and alpha 2-adrenoreceptor activation and prostanoid release. 2. Prostaglandin I2 (PGI2) and small amounts of thromboxane A2 (TXA2) are released from this preparation and can be monitored in the perfusate under basal and stimulated conditions. 3. Noradrenaline (NA) caused a significant increase in the release of PGI2 from the MAB of both WKY and SHR. Both basal and NA-stimulated PGI2 release were lower in the SHR, whereas pressor responses to NA were higher. Noradrenaline caused a very small increase in TXA2 release in the WKY only and the basal release of this prostanoid was again lower in the SHR. 4. Prazosin, an alpha 1-selective antagonist (10(-10), 10(-9), 10(-8) M) was more effective in blocking pressor responses to NA in the SHR than in the WKY, did not affect the NA-induced release of PGI2 in either group and abolished the small increase of TXA2 release in WKY. 5. Rauwolscine, an alpha 2-selective antagonist (10(-8), 10( 7), 10(-6) M) was more effective in reducing pressor responses to NA in the SHR than in the WKY. It abolished, from 10(-7) M upwards, the NA-induced release of PGI2 in the WKY and reduced it in the SHR. The NA-induced release of TXA2 was abolished in WKY. 6. The observed differences in the effects of rauwolscine and prazosin do not correlate with the effects of these antagonists on pressor responses since both reduce the latter but only rauwolscine abolishes the stimulated PGI2 release. 7. These results indicate that in the SHR, the mechanisms mediating the release of PGI2 from the MAB may be similar but not identical to those in the WKY. The observation that an increase in adrenergically induced pressor responses is not followed by an increase in PGI2 release, which is in fact reduced in the SHR, suggests a more complex regulation of this relationship which may have pathophysiological implications. PMID- 2908116 TI - [A case of polyarteritis nodosa associated with primary hypothyroidism]. PMID- 2908117 TI - Rationale for the management of calcific metamorphosis secondary to traumatic injuries. PMID- 2908118 TI - Interaction of Bordetella pertussis virulence components with neutrophils: effect on chemiluminescence induced by a chemotactic peptide and by intact bacteria. AB - The effect of secreted virulence components of Bordetella pertussis on chemiluminescence (CL) of rabbit peritoneal neutrophils was determined with the chemotactic peptide N'-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) or intact B. pertussis as the stimulus. Pertussis toxin (PT) inhibited the response to fMLP in a dose-dependent manner, although only after the neutrophils had been exposed to the toxin for greater than 15 min. Both filamentous haemagglutinin (FHA) and lipopolysaccharide (LPS) markedly enhanced the CL response to fMLP after greater than or equal to 15 min incubation with the neutrophils. Similar effects to those of B. pertussis LPS were also seen with smooth and rough LPS from Salmonella minnesota. With the lowest dose of each component which elicited a maximal effect on CL, the inhibitory effect of PT overrode the enhancing effect of FHA and B. pertussis LPS. Pre-incubation of neutrophils with PT, FHA or B. pertussis LPS caused a slight reduction in the subsequent CL response to virulent B. pertussis Tohama. Virulent (phase I, or X-mode) organisms of B. pertussis 18334 and B. pertussis Tohama induced greater neutrophil CL than their avirulent (C-mode) derivatives. There appeared to be an inverse correlation between bacterial hydrophilicity and the ability to induce neutrophil CL: X-mode bacteria were significantly less hydrophilic than C-mode organisms. Three mutants, the adenylate cyclase (AC)- and haemolysin (HLY)-deficient B. pertussis BP348, the FHA-deficient B. pertussis BP353, and the PT-deficient B. pertussis BP357, generated similar levels of CL and had similar hydrophilicity values. The hydrophilicity value of the avirulent mutant B. pertussis BP347 (deficient in AC, HLY, FHA and PT) and the CL induced by this strain were similar to those of B. pertussis C-mode organisms. Thus, the interaction of B. pertussis with neutrophils appears to be complex, reflecting both the alteration of leucocyte function by secreted virulence components of the organism and, in the absence of opsonins, the surface properties of the bacterium. PMID- 2908119 TI - Nucleotide sequence and characterization of a repetitive DNA element from the genome of Bordetella pertussis with characteristics of an insertion sequence. AB - A repeating element of DNA has been isolated and sequenced from the genome of Bordetella pertussis. Restriction map analysis of this element shows single internal ClaI, SphI, BstEII and SalI sites. Over 40 DNA fragments are seen in ClaI digests of B. pertussis genomic DNA to which the repetitive DNA sequence hybridizes. Sequence analysis of the repeat reveals that it has properties consistent with bacterial insertion sequence (IS) elements. These properties include its length of 1053 bp, multiple copy number and presence of 28 bp of near perfect inverted repeats at its termini. Unlike most IS elements, the presence of this element in the B. pertussis genome is not associated with a short duplication in the target DNA sequence. This repeating element is not found in the genomes of B. parapertussis or B. bronchiseptica. Analysis of a DNA fragment adjacent to one copy of the repetitive DNA sequence has identified a different repeating element which is found in nine copies in B. parapertussis and four copies in B. pertussis, suggesting that there may be other repeating DNA elements in the different Bordetella species. Computer analysis of the B. pertussis repetitive DNA element has revealed no significant nucleotide homology between it and any other bacterial transposable elements, suggesting that this repetitive sequence is specific for B. pertussis. PMID- 2908120 TI - The effect of cholecystokinin-related peptides on periodic pancreatic secretion in fasting dogs. AB - 1. The effect of cholecystokinin octapeptide (CCK-8) and pentagastrin on periodic pancreatic secretion was studied in fasting conscious dogs. 2. Both CCK-8 and pentagastrin, in small doses, prolonged the interval of periodic pancreatic secretion. Periodicity was disrupted by large doses of CCK-8 and pentagastrin. 3. CCK-8, at the dose which did not disrupt the cycle, raised the peak and the valley-to-valley means, but not the valley mean, of protein secretion in one cycle. Except at large doses, pentagastrin failed to increase the peak and valley mean, but increased mean, valley-to-valley protein secretion. Large doses of both pentagastrin and CCK-8 increased protein secretion at the valley. 4. The peak of periodic pancreatic protein secretion was about half the observed maximum protein response to CCK-8. 5. Atropine reduced pancreatic fluid and protein responses to small doses of CCK-8 to the levels of valleys. At large doses, however, both responses were augmented by atropine. Hexamethonium reduced the responses to any dose of CCK-8 to valley levels or less. Volume and protein responses to pentagastrin following atropine or hexamethonium were of similar magnitude to those at valleys. 6. It is concluded that CCK-8 and pentagastrin stimulate pancreatic enzyme secretion directly by acting on acinar cells and indirectly by modifying cholinergic ganglionic activities which control periodic secretion in conscious dogs. PMID- 2908121 TI - Outward rectification of inhibitory postsynaptic currents in cultured rat hippocampal neurones. AB - 1. Inhibitory postsynaptic potentials (IPSPs) and currents (IPSCs) were recorded from cultured hippocampal neurones of the embryonic rat at 22 degrees C, using the whole-cell patch-clamp technique with a low-Cl-, 145 mM-potassium gluconate solution in the patch pipette. Individual synaptic events were elicited at low frequency (0.05-0.1 Hz) by stimulating a presynaptic neurone either by direct intracellular current injection, or by applying a brief pulse of L-glutamate. 2. In target neurones voltage clamped at -40 mV, outwardly directed IPSCs of mean amplitude 0.23 nA were recorded. The IPSCs were depressed by the GABA antagonist bicuculline, and reversed polarity between -50 and -80 mV (mean -64 mV), as did current responses to gamma-aminobutyric acid. The IPSPs and IPSCs reversed as a single phase; no bicuculline-resistant 'late' synaptic event was observed. 3. The IPSCs had variable kinetics, with rise times between 1 and 5 ms (mean 2.9 ms) at 40 mV, and slower, monoexponential, decay phases (decay time constant, tau IPSC, 10-40 ms at -40 mV). In some cells, tau IPSC clearly increased with depolarization. 4. The IPSC reversal potential was -64 +/- 9 mV (n = 23) under the experimental conditions used; this suggests that the synaptically activated channels are approximately 25 times more permeable to Cl- than to the gluconate anion. 5. The peak conductance associated with the IPSC showed outward rectification. The synaptic conductance measured at -40 mV was 1.7 times greater than that measured at -100 mV; at -20 mV, synaptic conductance was 2.5 times greater than at -100 mV. This outward rectification can be explained by a constant field model under these experimental conditions of asymmetric Cl- concentrations. PMID- 2908122 TI - Role of alpha-adrenoceptors in constrictor responses of rat, guinea-pig and rabbit small arteries to neural activation. AB - 1. We have investigated the adrenoceptors mediating the force and electrical responses of rat mesenteric small arteries (i.d. 100-300 microns). Some mechanical experiments were also performed using guinea-pig and rabbit mesenteric small arteries. 2. Vessels were mounted on an isometric myograph and stimulated either with short (3 s) trains of electric field stimuli (ca. 0.2 ms pulse width) at 25 Hz (nerve stimulation) or with 10 microM-exogenous noradrenaline. 3. Nerve stimulation caused a force response equal to ca. 40% of the response to exogenous noradrenaline and, in the rat vessels, excitatory junction potentials (EJPs), which normally summated to give a depolarization of ca. 10 mV (although action potentials were sometimes seen). 4. Almost complete and reversible inhibition of the force responses of all vessels to both exogenous noradrenaline and to nerve stimulation was obtained using prazosin (0.1 microM) or phentolamine (1 microM). 5. Irreversible blockade of alpha 2-receptors enhanced the force response of all vessels to nerve stimulation by ca. 50%, but did not affect the force response of rat and guinea-pig vessels to exogenous noradrenaline. In the rabbit vessels this force response was abolished by alpha 2-blockade. 6. Following alpha 2-blockade, in the rat vessels the alpha-antagonists prazosin (0.1 microM), phentolamine (0.1 microM), phenoxybenzamine (0.01 microM) and benextramine (10 microM) all totally abolished the force response to exogenous noradrenaline, and inhibited the response to nerve stimulation by at least 80%. Similar effects of phentolamine were seen in the guinea-pig and, for the response to nerve stimulation, in the rabbit vessels. 7. In the rat vessels, alpha-adrenoceptor antagonists did not affect the EJPs, but did inhibit the small depolarization which resulted from several seconds of nerve stimulation. The ATP analogue alpha, beta-methylene-ATP (3 microM) abolished the EJPs, but only slightly reduced the force responses. 8. The results suggest that the force response to nerve stimulation of the rat mesenteric small arteries is mediated primarily through alpha-adrenoceptors, but also to a small degree through non-alpha-adrenoceptors, possibly ATP receptors. PMID- 2908123 TI - Electrophysiological analysis of the inactivation of sympathetic transmitter in the guinea-pig vas deferens. AB - 1. The properties of junction potentials evoked by nerve stimulation and by local application of drugs, and currents evoked by nerve stimulation, in the smooth muscle cells of the guinea-pig vas deferens have been investigated. The effects of temperature on these responses have been studied using intracellular and extracellular recording. 2. Local, brief (5-15 ms) application of 10(-4) M adenosine-5'-triphosphate (ATP) from glass micropipettes onto the surface of the vas deferens, using pressure pulses (103-206 kPa), elicited a depolarization of the smooth muscle cell membranes which closely resembled the nerve stimulation evoked excitatory junction potential (EJP). 3. Local application of 10(-4) M noradrenaline (NA) failed to produce any detectable membrane potential response. Junction potentials elicited by a mixture of 10(-4) M-ATP and 10(-4) M-NA (ratio by volume 1:50) in the drug ejection micropipette were similar in shape to those evoked by ATP alone. 4. Cooling the tissue from 35 to 25 degrees C did not significantly alter resting membrane potentials but resulted in a significant prolongation of the rising and decaying phases of the EJPs. Fifty per cent decay times for EJPs at 35 and 25 degrees C were (mean +/- S.D.) 236 +/- 20 and 434 +/- 30 ms respectively (P less than 0.01). 5. Extracellularly recorded excitatory junction currents (EJCs) elicited by nerve stimulation, believed to reflect the transmembrane current underlying the EJPs, were prolonged in parallel at low temperatures (50% decay times of EJCs at 35 and 25 degrees C: 11.73 +/- 3.94 and 26.15 +/- 8.4 ms, respectively, P less than 0.01). 6. Junction potentials evoked by locally applied, exogenous ATP were also significantly prolonged by cooling (50% decay times: 663 +/- 88 ms at 35 degrees C and 1955 +/- 79 ms at 25 degrees C, P less than 0.01). 7. Bath application of 10(-6) M-alpha,beta-methylene ATP, the enzymatically stable, desensitizing analogue of ATP, reversibly abolished nerve-evoked EJPs. Local application of 10(-6) M-alpha,beta-methylene ATP led to a prolonged depolarization of the smooth muscle cells lasting between 20 and 60 s. 8. Junction potentials elicited by locally applied alpha,beta-methylene ATP were not prolonged or otherwise significantly altered on cooling. The durations of the depolarizations were 46.0 +/- 12.1 s at 35 degrees C and 43.4 +/- 10.6 s at 25 degrees C (P greater than 0.1).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2908124 TI - Long-lasting modification of the synaptic properties of rat CA3 hippocampal neurones induced by kainic acid. AB - 1. The action of a short bath application of kainic acid (KA, 200-250 nM, 3-5 min) on the CA3 region of rat hippocampal slices has been studied with intracellular and extracellular recording techniques. 2. KA evoked bursts which persisted for 10-15 min. In addition, after KA, electrical stimulation of various inputs to CA3 which elicited an EPSP-IPSP sequence in control conditions evoked an EPSP followed by a burst. This evoked response persisted for several hours after removal of KA suggesting the occurrence of a long-lasting modification of the synaptic properties of CA3 neurones. 3. Intracellular recordings showed the spontaneous and evoked bursts to consist of five to ten action potentials riding on a depolarizing shift 10-25 mV in amplitude and 40-100 ms in duration. Both spontaneous and evoked bursts were followed by a long-lasting hyperpolarization 15-25 mV in amplitude and 1-1.5 s in duration. 4. We propose that both spontaneous and evoked synchronized bursts are generated by a polysynaptic network since: (a) intracellularly recorded bursts were synchronized with the bursts in extracellular field recording; (b) bursts disappeared when synaptic transmission or Na+ action potential were blocked by cobalt (1 mM) or TTX (1 microM) respectively; (c) bursts were suppressed by elevated divalent cation concentration; (d) burst occurrence was independent of the membrane potential of the cell; (e) the depolarization shift that underlies the bursts was a linear function of the membrane potential and reversed in polarity at 0 mV. In addition, the evoked bursts were all-or-none events with a variable latency. 5. Laminar profile analysis of the spontaneous and evoked bursts suggests that they were generated by synapses located on the distal apical segments of the dendrites of CA3 pyramidal cells. 7. The persistence of the evoked bursts was neither due to a persistent change in cell excitability nor to a long-lasting reduction in GABAergic synaptic inhibition. 8. Bath application of a high concentration of potassium (7 mM) also induced spontaneous and evoked bursts; the latter also persisted several hours after return to control medium. 9. The N-methyl-D aspartate (NMDA) antagonist, D-APV (D(-)-2-amino-5-phosphonovaleric acid) (30 microM), did not block the spontaneous discharges induced by KA or high potassium, but prevented the long-lasting effects on the synaptic responses.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2908125 TI - Evidence for adenosine triphosphate as an excitatory transmitter in guinea-pig, rabbit and pig urinary bladder. AB - 1. The effects of alpha,beta-methylene ATP (alpha,beta-MeATP) on membrane properties and excitatory junction potentials (EJPs) were examined in smooth muscle cells of the guinea-pig, rabbit and pig bladder. 2. Intracellular recording with microelectrodes was used to record membrane electrical activity from the guinea-pig bladder. ATP (10(-3) M) produced a rapid, large depolarization with a marked increase in spike frequency, while carbachol (10(-4) M) or acetylcholine (ACh; 10(-4) M) produced only a small or no depolarization with a smaller increase in spike frequency. alpha,beta-MeATP produced a similar response to that of ATP but at a much lower concentration (5 x 10(-6) M), and the response was transient even in the continuous presence of this agent. 3. Changes in the membrane potential and conductance elicited by alpha,beta-MeATP were also measured with the double sucrose-gap method. alpha,beta-MeATP (5 x 10(-6) M) depolarized the membrane and increased the membrane conductance in all three species, but both parameters returned to control values during continuous exposure to this agent. 4. Intracellular recording with microelectrodes showed that in the guinea-pig bladder treatment with alpha,beta-MeATP abolished the response to ATP, while the response to ACh was unchanged. 5. With the double sucrose-gap method, EJPs were elicited by transmural nerve stimulation of strips of the guinea-pig, rabbit and pig bladder and had spikes superimposed, leading to contractions. Desensitization of P2-purinoceptors by alpha,beta-MeATP (3-5 x 10( 6) M) abolished the EJPs and spikes, and reduced the contraction. Atropine (10( 6) M) alone did not alter the EJPs but reduced the contraction. Combined application of both agents abolished the contraction. 6. It is concluded that in the guinea-pig, rabbit and pig bladder ATP is an excitatory transmitter with ACh and EJPs are mediated by ATP. PMID- 2908126 TI - Adrenergic and opioidergic modulation of a spinal reflex in the decerebrated rabbit. AB - 1. In the decerebrated and spinalized rabbit, electrical stimulation of the sural nerve evokes a short-latency reflex in the ipsilateral ankle extensor gastrocnemius medialis (GM) which is tonically suppressed by endogenous opioids. In the present study we have investigated the inhibitory influences affecting this reflex in non-spinalized, decerebrated rabbits. 2. In non-spinalized rabbits, the thresholds and latencies of the sural-GM reflex were significantly higher than in spinalized preparations. The opioid antagonist naloxone and the alpha-adrenoceptor antagonist idazoxan potentiated the reflex in both preparations. Naloxone was significantly more effective in spinalized rabbits whereas idazoxan had a much larger effect in non-spinalized animals. 3. When the spinal cord was sectioned in the presence of naloxone alone, the GM reflex always increased in size. An ipsilateral hemisection of the cord was as effective as total section in this respect. When the section was performed in the presence of idazoxan and naloxone, the response usually decreased in size. 4. The alpha 2 adrenoceptor agonist clonidine depressed the reflex in spinalized rabbits, an action that was reversed by idazoxan but not by naloxone. 5. These data show that in the decerebrated, non-spinalized rabbit, the sural-GM reflex is tonically suppressed by endogenous opioids, presumably acting at the segmental level, and by an ipsilateral descending pathway which involves an alpha-adrenoceptor mediated synapse. Activity in this descending pathway masks the facilitatory effects of opioid antagonists on spinal reflexes in this preparation. PMID- 2908127 TI - Gastric vasodilatation and vasoactive intestinal peptide output in response to vagal stimulation in the dog. AB - 1. Gastric vasodilatation, relaxation, and vasoactive intestinal peptide (VIP) output in response to vagal stimulation were studied in anaesthetized dogs. 2. Stimulation of the peripheral end of the vagus nerve (10 Hz, 40 V, 0.5 ms) normally evoked a gastric contraction, but caused relaxation in atropinized dogs. There was no detectable difference between the electrical thresholds for activation of the vagal preganglionic excitatory and inhibitory motor fibres. 3. Vagal stimulation also evoked gastric vasodilatation, which was blocked by hexamethonium but not by combined muscarinic and adrenergic blockade. Vagal fibres evoking vasodilatation had higher thresholds to electrical stimulation than those evoking motor responses. 4. Both gastric motor responses to vagal stimulation increased with increasing frequency up to 10 Hz and a plateau between 10 and 40 Hz, but the vasodilator response was significantly reduced above 20 Hz. Vagal stimulation at 10 Hz caused an increase in gastric venous VIP output which was significantly reduced at 40 Hz. 5. Low-intensity vagal stimulation (10 Hz, 40 V, 0.05 ms) elicited gastric relaxation (40% of a maximum), with no release of VIP or gastric vasodilatation. 6. It is concluded that release of VIP in response to stimulation of the vagal innervation to the stomach in the dog is primarily vasodilating in action. PMID- 2908128 TI - The evolution of purinergic receptors involved in recognition of a blood meal by hematophagous insects. AB - Many blood feeders use adenine nucleotides as cues for locating blood meal. Structure-activity relationship of adenine nucleotides as phagostimulants varies between closely-related species of blood feeders. It is suggested that a preexisting diverse pool of nucleotide-binding proteins present in all living cells, serves as a source of receptor proteins for the gustatory receptors involved in blood detection. It is proposed that the selection of any such nucleotide-binding protein is random. PMID- 2908129 TI - The cell biology of mosquito vitellogenesis. AB - Insect vitellogenesis involves coordinated activities of the fat body and oocytes. We have studied these activities at the cellular level in the mosquito. During each vitellogenic cycle, the fat body undergoes three successive stages: 1) proliferation of biosynthetic organelles, 2) vitellogenin synthesis, 3) termination of vitellogenin synthesis and degradation of biosynthetic organelles by lysosomes. Analysis with monoclonal antibodies and radiolabelling demonstrated that the mosquito yolk protein consists of two subunits (200-kDa and 65-kDa). Both subunits are glycosylated, their carbohydrate moieties are composed of high mannose oligosaccharides. The yolk protein subunits are derived from a single 220 kDa precursor detected by an in vitro translation. Oocytes become competent to internalize proteins as a result of juvenile hormone-mediated biogenesis of endocytotic organelles. The yolk protein is then accumulated by receptor-mediated endocytosis. A pathway of the yold protein and factors determining its routing in the oocyte have been studied. PMID- 2908130 TI - Depletion of L3T4+ T lymphocytes during acute Trypanosoma cruzi infection abolish macrophage and B lymphocyte activation but not tissue inflammatory reaction. PMID- 2908131 TI - Takayasu's disease presenting as a thoracoabdominal aneurysm in an 18-year-old. PMID- 2908132 TI - [Dental soldering part VIII. Distortion of non-precious ceramometal fixed bridge during the soldering]. PMID- 2908133 TI - Low doses of ketazolam in anxiety: a double-blind, placebo-controlled study. AB - A multicenter, double-blind, between-patient trial comparing two doses of ketazolam (15 and 30 mg) with placebo, each given once daily, in the evening, to 92 outpatients affected by generalized anxiety disorders for at least 1 month, was carried out. After 1-week washout period 47 patients were randomized to ketazolam 15 mg, and 45 to placebo for 15 days (first period). At the end of this period, if the patient experienced a decrease on the total Hamilton Anxiety Rating Scale (HAM-A) of at least 25% of basal value, the treatment was kept unchanged for a further 15 days, otherwise 15 mg of ketazolam were added to the previous treatment (second period). Anxiety was rated after 2 and 4 weeks with the Italian HAM-A scale and with a 4-point scale (patient's assessment). Seventy eight patients completed the first period and 75 the whole study. During the first period the percentage of responders was almost identical in both treatment groups, but during the second period a further slight improvement was observed in the early placebo responders, while the HAM-A score of patients on ketazolam continued to improve significantly (p less than 0.01) throughout the study. Likewise a significant (p less than 0.001) difference between treatments was observed, on the 4-point scale, in the population as a whole (end of first period) as well as in responder patients (end second period). Tolerability was good, except in 1 patient on placebo, who was withdrawn from the study because of severe headache. PMID- 2908134 TI - Acute effects of bromazepam on signal detection performance, digit symbol substitution test and smooth pursuit eye movements. AB - Effects of 6 and 12 mg bromazepam on reaction time, stimulus sensitivity and response bias in a 1-hour visual attention task, on smooth pursuit eye movements, and on performance in the digit symbol substitution test (DSST) were investigated in 12 healthy male volunteers. It was a placebo-controlled, double-blind, crossover study that used repeated measures. Three saliva samples and a blood sample were taken for correlating drug concentration and performance. Bromazepam lowered stimulus sensitivity dose-dependently. Response times for hits and response bias were affected by the 12-mg dose only. DSST performance decreased dose-dependently. Smooth pursuit was equally impaired by 6 and 12 mg. Concentrations in serum correlated with concentrations in saliva, but serum and saliva concentrations did not correlate with task performance. PMID- 2908135 TI - Pharmacological and therapeutic profiling in drug innovation: the early history of the beta blockers. PMID- 2908136 TI - The difference in stress-induced analgesia in C57BL/6 and DBA/2 mice: a search for biochemical correlates. AB - The level of opioid peptides: beta-endorphin and dynorphin, binding to the mu and kappa opioid receptors and the analgesic response of those endogenous opioid systems to stress were investigated in two strains of mice: C57BL/6 (C57) and DBA/2 (DBA). The nociceptive threshold of DBA mice was higher than that of C57 mice. KD values for spinal mu receptors were lower in C57, while KD for cerebral kappa receptors were higher in this strain. DBA mice have significantly higher concentrations of dynorphin in the hypothalamus and neurointermediate lobe of the pituitary. Stress-induced analgesia was much greater in C57 than in DBA mice. In the hypothalamus both stress procedures depressed the concentrations of beta endorphin in C57, and dynorphin in DBA mice. The level of beta-endorphin increased in the neurointermediate lobe in C57 and in anterior lobe of the pituitary in DBA mice. In the spinal cord both stress procedures depressed the dynorphin level. The above data indicate that C57 and DBA mice differ in the endogenous opioid peptide content, stress-induced alteration and opioid receptor affinity, the effects which might correlate with their different responses to environmental factors and pharmacological agents. PMID- 2908137 TI - Electrophysiological effects of dopamine receptor stimulation in the hippocampus of Acomys cahirinus. AB - The effect of dopamine receptor agonists on the spontaneous bioelectrical activity of CA1 layer neurons in the hippocampal slice preparation from the Acomys and rat has been studied. The selective D1 receptor agonist SKF 38393 diminished the neuronal firing rate while the selective D2 receptor agonist LY 171555 (quinpirole) evoked an excitatory reaction, however, a great proportion of hippocampal neurons remained unresponsive to SKF 38393 and LY 171555. Both dopamine and apomorphine elicited mainly an increase in the neuronal discharge rate, the effect of the former having been antagonized by sulpiride. The present data reveal that the action of dopamine agonists on the hippocampal neurons of the Acomys generally resembles their activity on the rat hippocampal cells, however, the potency of dopamine and apomorphine in evoking the excitatory reaction is higher in the Acomys. PMID- 2908138 TI - A new parenteral emulsion for the administration of taxol. AB - Taxol (NSC-125973) is a poorly soluble plant product that exhibits excellent antimitotic properties. This study involves the development of a new formulation for taxol. The stability of taxol in a 50% triacetin emulsion as well as possible methods of intravenous administration of this dosage form was examined. A stable emulsion was found at taxol concentrations of 10 and 15 mg/ml of emulsion. The 50% triacetin emulsion showed an intravenous LD50 of 1.2 ml/kg in Swiss-Webster mice. The 10 mg/ml taxol formulation was demonstrated to be stable upon addition to 5% dextrose iv fluids provided that small packing systems were used. The taxol triacetin emulsion can also be intravenously injected at various rates, and it may prove to be a useful formulation for taxol. PMID- 2908140 TI - Embryonic origin of the diffuse endocrine system of the gastro-intestinal tract (II). PMID- 2908139 TI - Prion protein gene expression in cultured cells. AB - A single copy gene encodes both the scrapie (PrPSc) and cellular (PrPC) isoforms of the prion protein (PrP). Cultured cell lines were found to express the endogenous PrP mRNA at levels comparable to those observed in the brains of adult rodents; however, these cells were invariably found to express greatly reduced levels of PrP. In all the cell lines examined, PrP was undetectable by Western immunoblot analysis. These cells were also poor recipients for expression constructs linking the hamster PrP gene open reading frame to several strong eukaryotic promoters; stable clones derived by transfection of these expression vectors failed to show elevated expression of PrP. When extremely high levels of PrP mRNA were produced using either an insect baculovirus or a mammalian SV40 based vector, significant quantities of PrP were produced, although in both cases the proteins were apparently processed differently from the PrPC observed in brains. In an expression system using an SV40 late promoter vector in monkey COS 7 cells, a significant fraction of PrP was transported to the cell surface where PrPC is found in vivo. PrP synthesized by the baculovirus vector failed to induce scrapie in hamsters and did not possess the characteristics of the PrPSc isoform associated with infectivity. The SV40 late promoter vector system may permit experiments designed to elucidate the role of PrPSc during scrapie infection as well as the function of PrPC in normal metabolism. PMID- 2908141 TI - [Bone scintigraphy and echography in the diagnosis of rheumatic diseases]. PMID- 2908142 TI - [The hepatotoxicity of drugs]. PMID- 2908143 TI - [Dietary fiber and dietetics in diabetes mellitus]. PMID- 2908144 TI - [The validity of the major practical diagnostic criteria (anamnesis, skin tests and therapeutic tests) with implications for the combined treatment of type-I allergic asthma]. PMID- 2908145 TI - [Lipid indicators of risk of myocardial infarct]. PMID- 2908146 TI - [Analysis of the Brody effect in the electrocardiogram during effort]. PMID- 2908147 TI - [Endoscopic sclerotherapy of esophageal varices]. PMID- 2908148 TI - [Exocrine function in chronic pancreatitis]. PMID- 2908149 TI - [Clinical aspects of decompensated chronic kidney failure in diabetes mellitus (a study of 125 cases)]. PMID- 2908150 TI - [Determination of muscle enzyme activity in rheumatoid polyarthritis]. PMID- 2908151 TI - [Diagnosis of plasma hypercoagulability states]. PMID- 2908152 TI - [Anticalcium drugs in the treatment of arterial hypertension]. PMID- 2908153 TI - [The current status and outlook of the treatment of arterial hypertension with converting enzyme inhibitors]. PMID- 2908154 TI - [The role of intricate vascular and thrombocytic factors in precipitating acute coronary syndromes. Therapeutic implications]. PMID- 2908155 TI - [Protection of the ischemic myocardium]. PMID- 2908156 TI - [Doppler echocardiography]. PMID- 2908157 TI - [Calcium channel blockers with delayed effect in the treatment of arterial hypertension. A short-term study]. PMID- 2908158 TI - [Therapeutic possibilities in the recovery of work capacity in diabetics with arteriopathies of the lower limbs]. PMID- 2908159 TI - [Cerebrovascular lesions in diabetics (a study of 109 cases)]. PMID- 2908160 TI - Dopamine agonists for oral use. PMID- 2908161 TI - Core and paracores; some new chemoarchitectural entities in the mammalian neuraxis. AB - A study of the recent neuromorphological, neurophysiological and neuroethological literature, and data from the current research in our own laboratory have led us to a new classification of entities in the mammalian neuraxis. This classification comprises the core and the median and lateral paracores. The core of the neuraxis may be considered as a caudally extended limbic system. It extends throughout the central nervous system and, as its name implies, most of it is situated close to the ventricular cavity. This entity is characterized by the presence of (1) numerous diffuse grisea, (2) enormous amounts of thin, unmyelinated, varicose axons, many of which are arranged in diffuse fibre systems, (3) large numbers of different neuromediators, particularly neuropeptides, and (4) large numbers of neurons which concentrate estrogen and androgen hormones. Ethophysiological studies have shown that the core region contains numerous loci from which on stimulation quite characteristic behavioral patterns, like eating, drinking, fear, attack, reproductive behavior etc., can be elicited. The core region appears to be involved most directly in the organization of behavior and is of paramount importance for the regulation of processes aimed at the survival of the individual (organism) and of the species. The median and lateral paracores represent extensions of the core at the level of the brain stem. The median paracore includes the raphe nuclei, whereas the (bilateral) lateral paracore is constituted by a ventrolaterally extending lamella of tissue. Both paracores contain sets of monoaminergic cells giving rise to networks of fibres that pervade virtually all grisea of the neuraxis, i.e. the serotoninergic neurons in the median paracore and the catecholaminergic cells in the lateral paracore. The lateral paracore contains a series of grisea, including the substantia nigra, the ventral tegmental area, the nucleus reticularis parvocellularis, the tegmental pedunculopontine nucleus and the catecholaminergic cell groups A1, A2, A5, A7 and C1 and C2. It harbours a large bundle of loosely arranged, thin fibres, which forms a direct caudal continuation of the hypothalamic medial forebrain bundle. This lateral paracore bundle contains numerous catecholaminergic and peptidergic fibres. Three typical core centres, viz. the nucleus centralis amygdalae, the bed nucleus of the stria terminalis and the lateral hypothalamic area contribute substantially to this bundle. The lateral paracore contains, just like the core region, a large number of functionally defined centres related to integrated somatomotor and visceromotor responses. It is postulated that non-synaptic interneuron PMID- 2908162 TI - Synaptic and non-synaptic striatal dopamine D2 receptors: possible implications in normal and pathological behaviour. AB - Various levels of organisation in the central nervous system can be distinguished, ranging from the molecular, the cellular, the multicellular and the neuronal system level. The relationship between receptor function and behaviour is focussed to the dopamine D2 type receptor of the striatal complex in relation to extrapyramidal and limbic systems. In the striatal complex a striosomal and a matrix compartment can be distinguished. The matrix compartment can be considered as a part of the extrapyramidal system and is innervated by the motor cortex and by the dopaminergic neurons of the ventral tegmental, the dorsal substantia nigra and the retrorubral area. This compartment has a relatively high density of D2 receptors. The striosomes are innervated by e.g. the prelimbic cortex and dopamine neurones of the ventral part of the substantia nigra; here the density of D2 receptors are lower. Under normal conditions most of the D2 receptors are occupied by endogenous dopamine, and postsynaptic (e.g. cholinergic) function is therefore sensitive to antagonists; e.g. antipsychotics. Exposure to drugs such as amphetamine produces a substantial overflow of dopamine from nerve terminals leading to the activation of remote dopamine receptors, that may belong to the system that normally is not influenced by these nerve terminals (defined here as extra synaptic receptor activation). A loss of the normal spatial-temporal relationships may also occur during L-DOPA therapy in Parkinson's disease. In this illness, due to degeneration of dopaminergic innervation, several dopamine receptors have become non-synaptic. In these states of intoxication the normal spatial/temporal organization is lost and such a loss may contribute to behavioural impairments. PMID- 2908163 TI - Synaptic and non-synaptic communication in the brain: morphological, physiological and behavioral aspects. Proceedings of a workshop. Nijmegan, The Netherlands, November 29, 1988. PMID- 2908164 TI - Issues involved in the transmission of chemical signals through the brain extracellular space. AB - Two classes of substances exist within the extracellular space: energetic and informational. Examples of the former are glucose, dissolved oxygen and CO2 while the latter include excitatory amino acids, cathecholamines and opiates. The simple ions Na+ and Cl- are generally associated with energetic processes while extracellular K+ and Ca2+ tend to be informational in function. Local release of an informational substance brings about a concentration gradient that causes the substance to be dispersed in the extracellular space by diffusion. This process is modified relative to a free aqueous medium by the constraints of volume fraction, tortuosity and uptake. Volume fraction is defined simply as the fraction of a brain region that is extracellular. If a given quantity of substance is released into a region with a reduced volume fraction then the substance will reach a higher concentration than it would in a free medium. Tortuosity is related to the increase in the path length of the random walk of a diffusing particle due to the necessity to navigate around cellular obstructions. Tortuosity manifests itself as a decrease in the diffusion coefficient. Uptake represents the movement of a substance from the extracellular space to the intracellular. Since initially a concentration gradient exists in this direction and all membranes have some permeability some concentration-dependent uptake always occurs. In addition there exist specific carrier-mediated uptake processes for some substances such as amino acids or catecholamines. In some regions the dispersal process can be dominated by uptake rather than diffusion. While volume fraction, tortuosity and uptake have all been demonstrated by a technique based on the use of radiolabels and other methods, these classical techniques have limited spatial and temporal resolution. The advent of methods based on micro injection of substances by iontophoresis or pressure and subsequent detection with ion-selective microelectrodes (ISMs) or voltammetric microsensors (VMs) has opened a new window onto the dynamic local behavior of the extracellular space. In the last decade our laboratory and others have studied the migration of the test substances tetramethylammonium, tetraethylammonium, AsF6- and alpha naphthalene sulfonate, the endogenous ions K+ and Ca2+, the epileptogenic agent penicillin and the neurotransmitter dopamine. These studies have been carried out on the cerebellum and some other regions in a variety of species that include rat, turtle, skate and an intervertebrate, the cuttlefish.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2908165 TI - Synaptic and nonsynaptic release of neuromediators in the central nervous system. AB - Different types of release site were studied ultrastructurally with tannic acid and immunohistochemical techniques in the central nervous system (CNS) of the invertebrate pond snail Lymnaea stagnalis and in two neuromediator rich core regions in the CNS of the rat, viz., the median eminence (ME) and the mesencephalic central grey substance (MCG). In the CNS of the snail, release of the contents of the secretory granules could be clearly demonstrated in (1) neurohaemal axonterminals, (2) synapses and (3) in nonsynaptic release sites: neuronal processes without morphological synaptic specializations. In the ME, release of secretory products by exocytosis was found in neurohaemal axonterminals in the external part of the palisade layer and in nonsynaptic release sites in all other layers of the median eminence. It was found that oxytocine and vasopressin were released by exocytosis into the extracellular space from such (preterminal) nonsynaptic release sites. Serial section analysis revealed three types of fibre in the MCG, viz. (1) varicose fibres that made synaptic contacts with MCG dendrites on every varicosity, (2) fibres with two types of varicosity, viz. synapse-bearing varicosities and varicosities without synaptic specializations, and (3) varicose fibres without any synaptic specializations. It has been discussed that the nonsynaptic release sites in the CNS of the snail Lymnaea stagnalis, and the nonsynaptic varicosities in the rat brain are the morphological correlates of nonsynaptic communication in the CNS. The results further indicate that particular peptidergic neuromediators are released from such nonsynaptic varicosities, and may reach via the extracellular space receptors located at some distance. PMID- 2908166 TI - Interrelationships of cell-substrate and cell-cell adhesion structures in B chronic lymphocytic leukemia (B-CLL) cells. PMID- 2908167 TI - A study of early events during T cell differentiation in thymic grafted nude mice. PMID- 2908168 TI - Interactions between lymphoid cells and a thymic stromal cell line in vitro. AB - In the present study, we have optimalized the adherence assay to allow monitoring of the level of contact between thymocytes and a thymic epithelial cell line, E 5, in vitro. This type of interaction is not MHC-restricted, thus is unlikely to participate in the education of thymocytes to self. It was also shown that adherence does not vary from strain to strain, except for B6lpr/lpr immunodeficient mice which showed a markedly decreased adherence. This might be caused by the high level of L3T4-, Lyt-2- thymocytes in these mice (Davignon et al., 1985), since enriched double negative cells were shown not to adhere to E-5 cells. Preliminary characterization of adhering thymocytes suggests an heterogeneous mature phenotype. These cells appear around day 16 of fetal life and increase gradually until birth to remain constant throughout life. On the basis of contact duration, two populations of adhering thymocytes exist: one spontaneously detached after 1.5 hr, refractive to further adherence and the other which adheres for up to 14 hr. Contact between lymphoid and E-5 cells was shown to induce PHA responsiveness. PMID- 2908169 TI - Phenotypic changes in cultured rat dendritic cells: expression of IL-2 receptor, Thy-1 and other antigens. PMID- 2908170 TI - The effects of bacterial lipopolysaccharide (LPS) on high endothelial venules, T lymphocytes and interdigitating cells in mouse lymph nodes. PMID- 2908171 TI - Monocyte defect causes decreased autoMLR in multiple sclerosis patients. AB - We have recently demonstrated that peripheral blood monocytes from patients with multiple sclerosis (MS) have a defect in stimulating autologous and allogeneic T lymphocytes. This defect was found to correlate with disease activity. We report here that T4+ cells from MS patients proliferate weakly in the autologous mixed lymphocyte reaction (autoMLR). Furthermore, we provide direct proof that the depressed T4+ cell proliferation is due to the monocyte functional (stimulatory) defect. PMID- 2908172 TI - Should we be changing our operative strategies for the acute complications of peptic ulcer disease? AB - H2-receptor blockade for the treatment of peptic ulcer disease has been with us for over a decade and has led to a dramatic decrease in the number of operations being performed for chronic ulcer disease. Many surgeons feel that the swing away from ulcer surgery has gone too far. Nevertheless surgeons may have been slow to grasp the importance of H2-receptor blockers in the management of the acute complications of ulcer disease. PMID- 2908173 TI - Putative interaction of presynaptic dopamine and serotonin receptors modulating synaptosomal tyrosine hydroxylase activity in the nucleus accumbens of rats. AB - Inhibition of synaptosomal tyrosine hydroxylase activity by dopamine (DA) autoreceptors and serotonin (5-HT) heteroreceptors was used as a functional measure for the receptor activity in the nucleus accumbens of rats. Kinetic analysis of the concentration dependence of inhibition with and without antagonists indicates that the sensitivity of the autoreceptor to DA is significantly increased by blockade of the 5-HT heteroreceptor and vice versa. The results provide evidence for autoreceptor-heteroreceptor interactions at the presynaptic membrane level on dopaminergic nerve terminals. PMID- 2908174 TI - Calcium dependent reversible inactivation of erythrocyte transglutaminase by acrylamide. AB - Purified transglutaminase from human erythrocytes was shown to undergo time dependent inactivation by acrylamide added at millimolar concentration: this effect was wholly dependent on calcium ions and some protection was produced by glutamine substrates and GTP. The enzyme activity was recovered by addition of thiol based reducing agents, while ascorbic acid and sodium borohydrate were ineffective. These data are suggestive of an active site directed action of acrylamide. PMID- 2908175 TI - T-cell antigen receptor alpha chain polymorphisms in insulin-dependent diabetes. AB - Insulin-dependent diabetes is a chronic autoimmune disease probably mediated by T cells. We examined the alpha chain of the T-cell antigen receptor in two models of this illness (man and BB rat) to determine any association with autoimmune diabetes. We conducted a population study in man, using a human alpha chain probe, pGA-5, and restriction enzyme Bgl 11. Two allelic forms and three RFLP patterns, 2.8 and 3.0 kb homozygous and 2.8/3.0 heterozygous, were detected. There was no difference in the frequency of these RFLPs among the 50 Type I diabetic patients and 48 controls tested. BB rats develop a spontaneous T-cell mediated autoimmune diabetes. The diabetes has been linked in several breeding studies to an undetermined autosomal recessive gene causing T-cell lymphopenia. We were able to differentiate the T-cell antigen receptor alpha chain of the diabetic BB and control BBN rats using the restriction enzyme EcoR1 and a murine alpha chain probe, TT11. The BB rat had a haplotype characterized by the presence of 4.7 and 5.8 kb bands, and the absence of 1.4, 2.2, 2.6, 3.6, 3.9, 4.1, and 6.1 kb bands. In a breeding study with BB and BBN rats, diabetic animals of the F2 generation demonstrated no linkage with the BBs' alpha chain, nor was lymphopenia linked to the alpha chain of the BB rat. These results suggest that autoimmune diabetes is not linked to the T-cell antigen receptor alpha chain in the BB rat, nor is it associated with alpha chain constant region polymorphisms in Type I diabetes in man. PMID- 2908176 TI - WHO: from small beginnings. PMID- 2908177 TI - T lymphocytes from irradiation chimeras repopulated with 13-day fetal liver cells recognize antigens only in association with self-MHC products. AB - The restriction specificities of maturing thymocytes are determined by the Class II MHC antigens expressed by non-lymphoid thymic tissues. The proliferative response of mature T lymphocytes to antigen-presenting cells (APC) and antigen requires that the APC express the same MHC antigens as the thymus in which the T cells differentiated. Thus, in the two-way bone marrow chimera [A + B----(A x B)F1], T lymphocyte populations of A and B haplotypes have each acquired the potential to recognize antigens associated with either parental haplotype. In spite of the large body of work on MHC restriction, we still do not have a clear understanding of the mechanisms which impose self restriction. The chimeric model systems used previously to study MHC restriction have used adult bone marrow cells as the source of lymphoid precursors. During normal ontogeny, T cells are derived from precursors in the fetal liver and we felt that a direct comparison of T cells from fetal liver and bone marrow-repopulated animals would shed light on the development of MHC restriction specificities during T cell ontogeny in the thymus or prethymically. We found that parental T lymphocyte populations isolated from two-way fetal liver chimeras cooperated only with syngeneic APC, while those from bone marrow chimeras cooperated with APC of either parental haplotype. This suggests that fetal liver and bone marrow may not be equivalent sources of stem cells. Our results may be due to fundamental differences between thymocyte precursors in fetal liver and bone marrow, including the time course of their expression of T cell receptor gene products.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2908178 TI - Clonotypic analysis of the fetal B cell repertoire: evidence for an early and predominant expression of idiotypes associated with the VH 36-60 family. AB - Determining the mechanisms by which B cells develop that culminates in the generation of a diverse repertoire is critical to our understanding of how the immune response is regulated. The B cell specificity repertoire appears to be developmentally acquired in a predetermined, temporally ordered fashion. Thus, in the Balb/c mouse, the ontogenetic appearance of functional B cells specific for various hapten probes occurs in the order of dinitrophenol (DNP), fluorescein (Fl), and phosphorylcholine (PC). In addition, when the influenza virus hemagglutinin molecule was used as an antigen probe, similar conclusions were drawn regarding a patterned acquisition of the specificity repertoire. More recently, we have used a fetal organ culture system to show that hapten responsive B cells appear in the same predictable, temporal order in vitro. The importance of these studies was that the effects of environmental influences were minimized in the absence of circulation and cell migration, and therefore the results indicated that the patterned emergence of the specificity repertoire observed was largely the result of genetic regulatory processes. Recent molecular findings may relate to such genetic regulatory processes. The VH genes in Balb/c mice have been grouped into eight families based on sequence homology, and have been mapped relative to the constant region genes. Yancopoulos et al. and Perlmutter et al. have shown that the VH gene segments closest to the JH cluster, the VH1B 7183 family, are preferentially utilized in transformed fetal pre-B cell lines and in fetal B cell hybridomas. This led to the hypothesis that the developmental control of the expression of VH gene segments is related to chromosomal organization. A logical extension of these findings is that the programmed appearance of particular clonotypes in ontogeny may be explained, in part, by the preferential use of particular VH gene segments. However, to what extent the transformed B cell lines represent members of the functional expressed repertoire could not be evaluated. In the studies described herein, the fetal organ culture system was used to assess the early expressed repertoire at the clonotypic level using idiotypic analysis. Anti-DNP secreting clones were derived from fetal organ cultures and tested for the presence of two idiotypes, 36 and MOPC 460 (460). The 36 idiotype is a predominant DNP clonotype of the neonatal repertoire, while the 460 idiotype is a major cross-reactive idiotype of the adult DNP response.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2908179 TI - Human anti-idiotypic T lymphocyte clones are activated by autologous anti-rabies virus antibodies presented in association with HLA-DQ molecules. AB - The regulatory function of antigen-specific T cells in human antibody responses to protein and carbohydrate determinants of many viral and bacterial antigens has extensively been studied in systems involving in vitro triggering of B cells by antigens or polyclonal activators. Although amply documented in experimental murine models, the existence of T helper cells with receptor specificity for idiotypic determinants of B cell immunoglobulins has not been demonstrated in a human system. We are interested in T helper cell recognition of idiotypic determinants of virus-specific antibody, secreted by human B cells in response to viral antigens, and in the role which such idiotype-specific T helper cells play, alone or in concert with virus-specific T helper cells, to regulate the antibody response. Understanding of the function of different T helper cell subsets in an anti-viral antibody response and especially of the mechanisms of idiotype recognition by T cells is important for the development, and future application in man of idiotype vaccines, the potential of which has been indicated for different pathogens in several animal species. It was realized that for the efficient characterization of each of the T helper cell subsets, the availability of cloned populations of T cells would be inevitable. Furthermore, we argued that if, as predicted by Jerne, idiotype recognizing T helper cells are involved in physiological idiotype regulation in the course of an immune response--e.g., following encounter with virus--cloned populations of T cells should best be obtained by immunization protocols closely mimicking the physiological situation. In a previous report we described the induction of a secondary antibody response in human peripheral blood mononuclear cells (PBMC) in vitro by rabies virus antigen. This response was shown to be T helper cell dependent, and rabies virus specific T helper cell clones have recently been obtained in our laboratory. The present study describes the generation of cloned lines of anti-idiotypic T4+ cells from rabies virus immune PBMC restimulated with rabies virus antigen in vitro. The cloned T cell lines were found to respond to circulating autologous antibody exhibiting specificity to rabies virus, but not to rabies virus antigen. The clonal proliferation, induced by this "auto-anticlonotypic" antibody, was found to be preceded by modulation of the T3/Ti molecular complex and required presentation of the antibodies by antigen presenting cells in association with HLA-DQ molecules. This observation of MHC-restricted idiotype recognition by human T cells, may have important consequences for the understanding of the regulation of th PMID- 2908180 TI - [A study of the contents of vasoactive intestinal peptide, somatostatin and neurotensin in rectal mucosa in patients with inflammatory bowel disease]. PMID- 2908181 TI - Immunogenetics of Graves' ophthalmopathy. AB - We have performed an immunogenetic analysis of 53 patients with severe Graves' ophthalmopathy, 51 patients with Graves' disease but little or no clinically apparent eye disease, and 90 controls. The distribution of restriction fragment length polymorphisms was analysed in the three groups, using probes for the HLA DQ alpha and DR beta regions, the T-cell receptor C alpha, V alpha, C beta and J gamma genes and the immunoglobulin gene switch regions, S alpha and S mu. There was no abnormal distribution of these polymorphisms in either group of Graves' patients, or differences between the Graves' patients with or without eye disease. It was possible to assign HLA-DR types in most patients using the polymorphisms found after probing with DQ alpha and DR beta; there was no abnormal distribution of DR types (including HLA-DR3) assigned by restriction fragment polymorphisms in the two Graves' groups. These results fail to confirm the reported associations between ophthalmopathy and HLA-DR3 and between Graves' disease and the T-cell receptor C beta polymorphism; they also argue against a strong influence of Gm allotypes in Graves' disease since these genes are in linkage disequilibrium with the S alpha polymorphisms. The association of Graves' disease with HLA-DR3, defined hitherto using serological reagents, may be less strong than previously described. PMID- 2908182 TI - Degradation of oxidatively denatured proteins in Escherichia coli. AB - When exposed to oxidative stress, by oxygen radicals or H2O2, E. coli exhibited decreased growth, decreased protein synthesis, and dose-dependent increases in protein degradation. The quinone menadione induced proteolysis when cells were incubated in air, but was not effective when cells were incubated without oxygen. Anaerobically grown cells also exhibited significantly lower proteolytic capacity than did cells that were grown aerobically. Xanthine plus xanthine oxidase (which generate O2- and H2O2) caused a stimulation of proteolysis which was inhibitable by catalase, but not by superoxide dismutase: Indicating that H2O2 was responsible for the increased protein degradation. Indeed, H2O2 alone was effective in inducing increased intracellular proteolysis. Two-dimensional polyacrylamide gel electrophoresis of [3H]leucine labeled E. coli revealed greater than 50% decreases in the concentrations of 10-15 cell proteins following H2O2 or menadione exposure, while several other proteins were less severely affected. To test for the presence of soluble proteases, we prepared cell-free extracts of E. coli and incubated them with radio-labeled protein substrates. E. coli extracts degraded casein and globin polypeptides at rapid rates but showed little activity with native proteins such as superoxide dismutase, hemoglobin, bovine serum albumin, or catalase. When these same proteins were denatured by exposure to oxygen radicals or H2O2, however, they became excellent substrates for degradation in E. coli extracts. Studies with albumin revealed correlations greater than 0.95 between the degree of oxidative denaturation and proteolytic susceptibility. Pretreatment of E. coli with menadione or H2O2 did not increase the proteolytic capacity of cell extracts; indicating that neither protease activation, nor protease induction were required.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2908183 TI - Synaptic potentials in rat locus coeruleus neurones. AB - 1. Intracellular recordings were made from locus coeruleus neurones in a slice of tissue cut from the rat pons. A depolarizing postsynaptic potential (PSP) followed electrical stimulation of the slice surface; the latency was 1-3 ms and the duration was 50-200 ms. 2. The reversal potential of the PSP (estimated by extrapolation from potentials between -60 and -90 mV) was -27 mV when the recording electrodes contained potassium chloride, and -36 mV when electrodes contained potassium acetate or methylsulphate. 3. Kynurenic acid depressed the PSP amplitude by up to 60%. The residual PSP reversed polarity at -50 mV (extrapolated, potassium chloride in electrodes) or -70 mV (observed, potassium methylsulphate in electrodes): it was blocked by bicuculline (10 microM). 4. Exogenously applied gamma-aminobutyric acid (GABA) depolarized cells when the recording electrode contained potassium chloride (reversal potential was -45 mV) and hyperpolarized cells when the recording electrode contained potassium methylsulphate (reversal potential was -70 mV). 5. In the presence of bicuculline, the residual PSP was blocked by kynurenic acid, whereas DL-2-amino-5 phosphonovaleric acid (2-APV) reduced its amplitude to 80% of control. 6. Exogenously applied glutamate, quisqualate and N-methyl-D-aspartate (NMDA) all caused a membrane depolarization (or an inward current under voltage clamp) which reversed polarity at about 0 mV. These effects were blocked by kynurenic acid (500 microM); 2-APV (50 microM) selectively blocked the effect of NMDA. 7. The results indicate that the PSP evoked by focal stimulation within the nucleus locus coeruleus results from an excitatory amino acid acting predominantly at non NMDA receptors, and from GABA acting at GABAA receptors. PMID- 2908184 TI - Transmitter release at mouse motor nerve terminals mediated by temporary accumulation of intracellular barium. AB - 1. In isolated mouse diaphragm, tetanic nerve stimulation in the presence of Ba2+ causes an increase in frequency of MEPPs which continues as an after-discharge or 'tail' of raised MEPP frequency that subsides over a period of seconds, in addition to EPPs of low quantal content. 'Ba2+ tails' are also seen with focal depolarization of nerve terminals in the presence of tetrodotoxin. 2. The development of 'Ba2+ tails' could be inhibited or blocked by neomycin, raised Mg2+, or Cd2+ present at the time of stimulation; the presence of the blocking substance during the tail itself had no effect. 3. The time course of MEPP frequency changes during and after stimulation could be expressed as a simple exponential process, with the same time constant for both the rise and the fall, by taking as the time-dependent variable the nth root of MEPP frequency, n being 4 or 5. The time constant (tau) derived from the rate of fall of the 1/4 power of MEPP frequency during the tail was at most junctions between 3 and 6 s, and apparently unaffected by concentration of Ba2+, or of Ca2+, or by tonic depolarization of the nerve terminal. 4. The intensity of 'Ca2+ tails' was graded steeply with the number of stimuli applied, but was nearly independent of stimulus frequency, when train duration was kept brief compared to tau, i.e. about a second or less. The nth root of the number of MEPPs at a given time period in the tail was linearly related to the number of stimuli, when n was chosen to be 4 or 5. 5. The above data are consistent with a model in which (a) with each nerve impulse in a train there occurs the same entry of Ba2+ into the terminal, (b) transmitter release (MEPP frequency) is proportional to the fourth or fifth power of [Ba2+] at critical sites within the nerve terminal, (c) the Ba2+ leaves these sites as a first-order process with a time constant of a few seconds. Compared to Ca2+, Ba2+ persists longer but has lower potency. 6. With variation of external [Ba2+] over the range 50 microM to 6.4 mM, apparent Ba2+ entry per nerve impulse grew linearly with concentration. 7. Evidence is presented indicating that intraterminal Ba2+ can 'co-operate' with Ca2+ or La3+ in promoting transmitter release. PMID- 2908185 TI - Some factors affecting isolation of Clostridium tetani from human and animal stools. AB - Clostridium tetani was isolated from human and animal stools at the following rates [95% confidence interval (CI)]: Human, 0% (1.5-0); horse, 1% (5-0); cow in cowshed, 4% (10-1); cow in pasture, 8.3% (17-1), calf in pasture, 0% (7-0); dog, 2% (11-0) and sheep in pasture, 25% (44-14). Quantification of C. tetani in 16 animal stools positive for the bacillus was impossible in most cases, as the number of tetanus bacilli present was not large enough for this purpose. Contaminating anaerobic and facultative anaerobic bacteria in human and animal stools, i.e., C. perfringens and Streptococcus sp., Group G, inhibited isolation of C. tetani from these materials, particularly at the step of isolation employing its swarming character. PMID- 2908186 TI - Anaphylactic sensitivity and immunity to Schistosoma mansoni in mice. PMID- 2908187 TI - Filariasis programme--Recife--Brazil. PMID- 2908188 TI - AIDS Conference in Montreal is a first for Canada. PMID- 2908189 TI - [Gastro-entero-pancreatic production and hepatic uptake of gastrin and somatostatin in the preruminant calf receiving milk proteins or milk serum]. AB - In preruminant calves total splanchnic production of immunoreactive somatostatin and gastrin did not change when casein was replaced by whey protein in the diet, but gastrin secretion was more rapid for the first 3 postprandial hours. Loss during passage through the liver was equivalent to splanchnic production for somatostatin, but was very low for gastrin. PMID- 2908190 TI - Cisapride induces clustered spikes and irregular spiking of the small intestine of the rat. AB - The aim of the present study was to investigate the effect of cisapride on the myoelectric activity of the small intestine in the rat. Intestinal myoelectric activity of fasted conscious rats was monitored by three bipolar electrodes chronically implanted at 5, 15 and 25 cm distal to the pylorus and connected to an EEG amplifier. In the basal state, regularly occurring migrating myoelectric complexes (MMCs) and clustered spikes were registered. Cisapride at doses of 0.5 4.0 mg-1 i.v. did not affect the MMCs, but at 8 mg kg-1 i.v. the regular MMCs were replaced by irregular spiking activity (p less than 0.05). Concomitantly cisapride increased the occurrence of clustered spikes and abbreviated the interval between them in a dose-dependent manner (p less than 0.05), without affecting their duration. Hexamethonium at a dose of 10 mg kg-1 i.v. abolished the MMCs as well as the stimulatory effect of ciSapride (4 mg kg-1). Atropine at a dose of 1 mg kg-1 i.v. did not affect the MMCs but blocked the stimulatory effect of cisapride (4 mg kg-1). It is concluded that cisapride induces clustered spikes and irregular spiking. These effects require intact cholinergic pathways, involving both muscarinic and nicotinic receptor mechanisms. PMID- 2908192 TI - [Pretumor markers in experimental liver cancer and its biological significance]. PMID- 2908191 TI - Mammalian homeobox-containing genes: genome organization, structure, expression and evolution. AB - Mammalian homeo box-containing genes have been isolated by their sequence similarity to Drosophila homeotic selector genes. About 20 murine homeo box genes have been identified to date and their expression and structural organization has been described in detail. Most homeo box gene loci are organized in at least three major gene clusters in the mouse and human genome. The structure of homeo box genes within these clusters is very similar and in this paper the murine Hox 2.2 gene will be discussed as an example. Homeo box genes are expressed in region specific patterns during different stages of vertebrate development and almost all mammalian homeo box genes are expressed in the central nervous system (CNS) of the developing embryo. Within the developing CNS of mouse embryos the anterior boundaries of expression are specific for each gene. Comparisons of nucleotide and amino acid sequences as well as the analysis of the structural organization of murine and human homeo box genes reveal strong paralogous relationships between genes in different clusters. These findings suggest that the homeo box gene clusters evolved in two steps. First, an ancestral gene cluster was created by duplications of individual genes along one linkage group and in a subsequent step duplications of the ancestral gene complex gave rise to the three (or possibly four) gene clusters observed in mouse and human to date. The possibility of the homeo box genes representing a functional array of genetic switches will be discussed. PMID- 2908193 TI - Measurement of the transfer of the nitrogen moiety of intestinal lumen glutamic acid in man after oral ingestion of l-[15N]glutamic acid. AB - 1. The measurement of the intestinal metabolism of the nitrogen moiety of glutamic acid has been investigated by oral ingestion of l-[15N]glutamic acid and sampling of arterialized blood. 2. Measurements have been made in six normal adults weighing an average of 72.8 kg ingesting 100 mg of l-[15N]glutamic acid after an overnight fast. 3. Measurement of the enrichment of arterial glutamic acid, glutamine and alanine was by gas chromatography-mass spectrometry. Isotopic enrichment of the amino acids was followed for 150 min after the ingestion of the amino acid. 4. Arterialized venous blood amino acid concentrations, measured by h.p.l.c., demonstrated no significant changes during the course of the experiment. 5. From the observed appearance of label in arterialized glutamic acid, alanine and glutamine, little luminal glutamic acid reaches the extracellular pool. The majority of the administered nitrogen label appears in the arterial alanine and glutamine components. PMID- 2908194 TI - Life, evolution, and the pursuit of single photon sensitivity. AB - Evolutionary forces have designed a large family of rod and cone photoreceptors, each member of which suits the lifestyle requirements and circadian patterns of a particular species. The three-segment architecture of signal transduction is conspicuous in the biochemistry of photoreceptors and supports their demonstrated properties of extreme sensitivity, low noise levels, extended dynamic range, and light adaptation. The designs elaborated by evolution reflect a gradual process of modification, with the sequential elaboration of layers of control and refinements in control. The end results of this long evolutionary labor are the functional efficiency and dynamic range that give the rod its utility. Our conceptual problems in deriving observed rod properties from the collective features of known rod gene products may well give way when we have learned more about the true composition and topology of the outer segment gene set and both bound and free nucleotide concentrations. The invertebrates have developed alternative solutions to the problems of photoreceptor sensitivity and wide dynamic range. The vertebrate rod represents a truly optimized way to capture and interpret low-intensity photon signals. One may anticipate, with some enthusiasm, those molecular and kinetic data that will permit an understanding of how cones differ from rods and how release from the requirement for single photon detection has shaped the design of this wavelength-specific companion photoreceptor. The utilization by evolution of the three-segment architecture of GTP-dependent signal transduction for other modalities of sensory perception, such as olfaction (Lancet et al., this volume) and gustation (Jones et al., this volume), is certainly a reasonable and successful choice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2908195 TI - Effects of nitrovasodilators, endothelium-dependent vasodilators, and atrial peptides on cGMP. AB - The interactions of the nitrovasodilators, endothelium-dependent vasodilators, and atrial peptides with cGMP synthesis have proved to be useful and important leads to the functions of cGMP and signal transduction mechanisms. Although considerable progress has been made, many important questions remain to be answered. Nevertheless, the guanylate cyclase-cGMP system clearly represents an important second-messenger system that mediates the effects of numerous agents. PMID- 2908196 TI - Analysis of serum response element function in vitro. PMID- 2908197 TI - Cooperative action of the glucocorticoid receptor and transcription factors. PMID- 2908198 TI - Anti-oncogenes and the negative regulation of cell growth. PMID- 2908199 TI - Influence of p21ras on phosphatidylinositol turnover. PMID- 2908200 TI - The membrane form of guanylate cyclase. PMID- 2908201 TI - Tissue effects on the expression of serotonin, tyrosine hydroxylase and GABA in cultures of neurogenic cells from the neuraxis and branchial arches. AB - The phenotypically diverse neurones of the enteric nervous system are developmentally derived from precursors that migrate to the bowel from the vagal and sacral regions of the neuraxis. In order to gain insight into the generation of enteric neuronal diversity, we examined the expression of serotonin (5-HT), tyrosine hydroxylase and GABA in vitro. In the mature avian intestine, intrinsic neurones contain 5-HT or GABA but not tyrosine hydroxylase. These markers were demonstrated immunocytochemically, singly or simultaneously. All three phenotypic markers developed in cultures of cranial, vagal or truncal neural crest when the cultures were grown in enriched medium, containing horse serum and chick embryo extract; however, 5-HT and GABA, but not tyrosine hydroxylase-immunoreactive cells, also developed in cultures that were grown in partially defined medium. Tyrosine hydroxylase immunoreactivity was seen when partially defined medium was supplemented with nerve growth factor (NGF). Cultures of branchial arches (III and IV) contained cells that displayed tyrosine hydroxylase immunoreactivity, but not that of 5-HT- or GABA-; however, 5-HT immunoreactivity was seen when branchial arches were cocultured with aneuronal hindgut (from 4-day chick embryos). Cultures of cells from chick gut dissociated at 7 days contained tyrosine hydroxylase as well as 5-HT and GABA immunoreactivities; however, no cultures of bowel dissociated at 8 days or later expressed tyrosine hydroxylase immunoreactivity. When neuraxial cells were cocultured with branchial arches or heart instead of gut, no 5-HT-immunoreactive cells were seen; nevertheless, the further addition of explants of gut to the heart/crest cocultures did permit the expression of 5-HT immunoreactivity. These results are consistent with the hypotheses that precursors with the potential to give rise to cells that express 5-HT, GABA and tyrosine hydroxylase are found at several levels of the neuraxis; however, the ability to express these phenotypes may be suppressed either while the crest cells are migrating (for example, 5-HT and GABA expression by crest cells passing through the branchial arches) or in their final destination (for example, tyrosine hydroxylase in the gut). This suppression may be transient and reversed by the microenvironment of the target organs. PMID- 2908202 TI - A gene with sequence similarity to Drosophila engrailed is expressed during the development of the neural tube and vertebrae in the mouse. AB - The mouse genes En-1 and En-2 display sequence similarity, in and around the homeobox region, to the engrailed family in Drosophila. This paper describes their pattern of expression in the 12.5-day mouse embryo as determined by in situ hybridization. En-2 is expressed in a subset of cells expressing En-1. Both genes are expressed in the developing midbrain and its junction with the hindbrain. In addition, En-1 is expressed in the floor of the hindbrain, a restricted ventrolateral segment of the neural tube throughout the trunk and anterior part of the tail, the dermatome of tail somites, the centrum and costal processes in developing vertebrae, a restricted region of facial mesenchyme and the limb-bud ectoderm. Supplementary studies of 9.5-day and 10.5-day embryos showed that the same pattern of expression pertained in the neural tube, but that expression in the somites is at first confined to the dermatome and later found at a low level in restricted sclerotomal regions. Both genes are expressed in restricted domains which do not cross tissue-type boundaries. In several instances, however, boundaries of expression lie within morphologically undifferentiated tissue. These results suggest that En-1 and En-2 may be involved in the establishment or maintenance of the spatial integrity of specific domains within developing tissues. PMID- 2908203 TI - Development of a solid phase RIA for human plasma somatostatin. AB - Somatostatin is widely distributed in tissues of biological fluids. In the present study we tested the validity of a new radioimmunoassay by a solid phase immunoextraction. Sensitivity was 1.8 pg/mL and the within-assay precision with two different pools of human plasma was 12.2% (CV) at a concentration of 19.2 +/- 2.34 pg/mL (mean +/- SD) and 11.9% at 8.53 +/- 1.02 pg/mL. The between assay precision was 14.2% (CV) at a concentration of 11.8 +/- 1.68 pg/mL. The accuracy was good as tested by the dilution test (slope: 0.956, Y-intercept 3.07 pg/mL, r = 0.997) and the recovery test (slope: 1.008, Y-intercept 2.22 pg/mL, r = 0.999). The method resulted in good correlation with a current extraction method (no. 65, y = 1.45 + 0.975 x, r = 0.862, P less than 0.001). Basal value of somatostatin in the plasma of 32 normal subjects was 11.5 +/- 5.80 pg/mL (mean +/- SD). PMID- 2908204 TI - Microcycle conidiation in submerged cultures of Penicillium cyclopium attained without temperature changes. AB - Microcycle conidiation in shaken cultures of Penicillium cyclopium M 79 was induced at 24 degrees C without any shock treatment. The occurrence of a microcycle depended on the presence of an organic acid (especially glutamic acid) in combination with glucose, low phosphate concentration, light and sufficient aeration. Absence of glucose and/or lowered aeration evoked vegetative growth. A synchronous and homogeneous microcycle required a certain relationship between the number of inoculated conidia and the concentration of the organic acid in the medium; the optimum was at 0.08 nmol acid per conidium. Higher values stimulated normal vegetative growth. A shortage or absence of the organic acid led to an atypical growth. The effect of organic acid can be partially replaced by addition of 2% (w/v) CaCO3. Addition of NH+4 in concentrations higher than 6 mM to cultures with glutamate or glutamine evoked vegetative growth. PMID- 2908205 TI - Detection of fimbriae and fimbrial antigens on the oral anaerobe Bacteroides gingivalis by negative staining and serological methods. AB - We screened 63 clinical isolates of Bacteroides gingivalis from eight different laboratories for the presence of fimbriae by negative staining and by immunological methods. Techniques used were bacterial agglutination, Ouchterlony immunodiffusion and Western immunoblotting analysis using rabbit anti-fimbriae and anti-fimbrilin sera raised against fimbriae and fimbrilin (a constituent protein of B. gingivalis fimbriae) from B. gingivalis strain 381. In 49 of the 51 strains tested, fimbriae were clearly detected by negative staining, and 30 (60%) of the fimbriate strains were positive in all three of the immunological assays. A total of 37 strains (75%) were positive by immunoblotting analysis, which was the most reliable of the serological methods used in this study. The study shows that the majority of B. gingivalis strains are fimbriate, and that these fimbriae are immunologically related to the fimbriae of B. gingivalis strain 381. Molecular heterogeneity of fimbrilin was discovered by the immunoblotting analysis, when different strains were compared. With most of the strains, including strain 381, the antifimbrilin serum reacted with a protein of apparent molecular mass 43 kDa, but with 15 strains the immuno-reactive protein had an apparent molecular mass of 46 kDa. PMID- 2908206 TI - [Polyarteritis nodosa diagnosed by duodenopancreatectomy]. PMID- 2908207 TI - Subcellular localization of muscarinic effects on enzymes of cyclic nucleotide metabolism in cultured corneal epithelial cells of the rabbit. AB - Activities of adenylate and guanylate cyclases and cAMP and cGMP phosphodiesterases (cAPDE, cGPDE) were assayed in cell homogenates and subcellular fractions of cultured rabbit corneal epithelium, and effects of carbamylcholine on enzyme activities in each fraction were evaluated. Activity of cyclases and phosphodiesterases was detectable in control incubations of homogenates, nuclei, the mitochondrial/lysosomal fraction, microsomes, and cytosol, although microsomal guanylate cyclase represented a very small proportion of the total cellular activity. In homogenates, carbamylcholine significantly elevated guanylate cyclase and cAPDE and reduced cGPDE activity. In mitochondria/lysosomes, guanylate cyclase was elevated and cGPDE reduced, but the drug did not alter cAPDE activity. In microsomes, carbamylcholine enhanced cAPDE but did not alter guanylate cyclase of cGPDE activity. In the soluble cytoplasmic fraction the drug reduced guanylate cyclase activity. The purified nuclear fraction exhibited substantial activity of cyclases and phosphodiesterases. Carbamylcholine significantly elevated activity of nuclear guanylate cyclase and cAPDE and significantly reduced nuclear cGPDE activity. The drug did not significantly alter adenylate cyclase in homogenates or in any cell fraction. The presence of activity of enzymes of cyclic nucleotide metabolism in the cell nucleus and the sensitivity of nuclear guanylate cyclase, cAPDE and cGPDE to carbamylcholine, which in the same concentration range enhances activity of DNA and RNA polymerases, suggested the hypothesis that effects on cyclic nucleotide dependent phosphorylation of nuclear proteins might be among regulatory mechanisms by which the drug alters rates of replication and transcription in corneal epithelial cells. PMID- 2908208 TI - Diuretic drugs as risk factors in cataractogenesis. AB - The use of diuretic drugs, which previously has been found to be associated with the incidence of cataract, is further investigated to elucidate the nature of the association. Diuretic drugs with different modes of action are considered separately. The degree of association of each correlates with the mean plasma urea level which itself is associated with cataract. However, the association is with cataract in general rather than with any specific type of lens opacity. PMID- 2908209 TI - [Dental soldering (Part IX). Tensile strength of nickel-chromium base metal presoldered joints, soldered by focused energy of infra-red]. PMID- 2908210 TI - [Stress and postoperative analgesia]. PMID- 2908211 TI - [Use of DNA polymorphism in the diagnosis of human genetic diseases]. PMID- 2908212 TI - [Periarteritis nodosa following vaccination against hepatitis B]. PMID- 2908213 TI - A study on Chinese phenylalanine hydroxylase gene restriction site polymorphism. AB - Human phenylalanine hydroxylase (PAH) cDNA was applied as a hybridization probe to analyzing the following 8 restriction fragment length polymorphisms (RFLP) in the PAH genes of 80 normal and 28 phenylketonuric Chinese patients: BglII, 3.6 kb/1.7 kb; EcoRI, 17 kb/11 kb; EcoRV, 30 kb/25 kb; HindIII, 4.2 kb/4.0 kb; MspIa, 23 kb/19 kb; MspIb, 4.0 kb/2.2 kb; PvuIIa, 19 kb/6.0 kb and PvuIIb, 11.5 kb/9.1 kb. The frequencies of the above RFLP in normal Chinese and PKU patients are: 0.13, 0.83, 0.77, 0.81, 0.12, 0.04, 0.70, 0.10 and 0.12, 0.93, 0.89, 0.81, 0.04, 0, 0.69, 0.04, respectively. This study reveals significant differences between the frequencies of individual RFLPs when these values are compared with those of the Caucasians. Finally, the detection of RFLPs in the PAH gene in the Chinese population will permit prenatal diagnosis of PKU in China. PMID- 2908214 TI - Effects of urethane administration on somatostatin receptors in rat cerebral cortex and pituitary. PMID- 2908215 TI - Influence of anesthetic agents on the release of growth hormone induced by growth hormone-releasing hormone in rats. PMID- 2908216 TI - [Effects of chlordemethyldiazepam on blood cortisol during surgical stress]. AB - The pre-operative plasma cortisol levels in 16 male patients undergoing plastic reconstructive surgery were studied. 8 patients received chlordesmethyldiazepam 0.1 mg/kg-1 i.v. (group C), 8 sodium thiopental 5 mg/kg-1 i.v. (group T) in anaesthesia induction. All patients were premedicated by diazepam 0.15 mg/kg-1 by mouth 90 min before anaesthesia induction and atropine 0.007 mg/kg-1 i.v. just before induction, and received succinylcholine 1 mg/kg-1 i.v. and an endotracheal tube for mechanically controlled ventilation. Anaesthesia maintenance was assured by isoflurane 0.5-2.5% in a N2O/O2 (2/1) gas mixture. Blood samples were collected from each patient at the following times: 24 h before surgery (t0); 30 min after skin incision (t1); 30 min after extubation (t2). Significant variations of blood cortisol levels have not been shown. PMID- 2908217 TI - The ultrastructure of the thyroid parafollicular cells of the marmot (Marmota marmota). Immunocytochemical localization of calcitonin and somatostatin. AB - We studied the topographical and ultrastructural characteristics of the parafollicular cells in the Marmota marmota and their seasonal changes. The parafollicular cells, together with the follicular cells, form the follicular epithelium occupying a peculiar basal position. Furthermore these cells are characterized by a clear cytoplasmic matrix and well developed cytoplasmic organelles. The latter synthesize and condense the secretory product which ultrastructurally is organized in secretory granule-vesicles with a scarcely electron-dense cottony content. Histochemically the secretion consists in a proteic complex (rich in alpha-amino acids and sulphonate proteins) with a minor glucidic component. The above metabolic activity closely relates with the seasonal metabolic changes and namely with calcium metabolism. The immunocytochemical reactions revealed the presence of calcitonin and, to a lesser extent, somatostatin. The morphological findings were compared with those observed in other hibernating mammalians and related to the calcium homeostasis. PMID- 2908218 TI - [Treatment with bromperidol in schizophrenic patients]. AB - The antipsychotic action, and undesirable effects of Bromperidol were examined over a 3-month period on an open clinical trial with 33 schizophrenic patients. Bromperidol was administered at an initial dose of 2.5 to 10 mg once a day. The results obtained according to BPRS, and CGI parameters after 2 weeks' time, and 1, 2, and 3 months' time showed a marked improvement in most of the scored psychiatric symptoms. Bromperidol has a potent antipsychotic action, and some stimulating properties on activity which make it very useful when increasing patients' motivation, and resocialization is at stake. Its general tolerance was very good. Nine patients (27%) presented mild extrapyramidal side-effects and anticholinergic medication controlled easily enough. PMID- 2908219 TI - Transglutaminases and their regulation: implications for polyamine metabolism. PMID- 2908220 TI - The enhancing effect of cyclosporine A and sulfasalazine on the prevention of rejection in rat cardiac allografts. AB - Sulfasalazine (SASP) has been used for many years as a disease-modifying agent in inflammatory bowel disease and in rheumatoid arthritis. However, its mode of action is not entirely clear. Evidence has been accumulated which indicates that its efficacy is due to an immunomodulatory effect. In the present communication, we report that SASP has an immunomodulatory capacity in an experimental rat cardiac allograft model. A combination of 100 mg/kg per day of SASP given orally until rejection and 10 mg/kg per day of cyclosporine A (CyA) given orally for 10 days resulted in a significantly increased graft survival time as compared to that in animals given CyA alone. PMID- 2908221 TI - Conformational analysis of nisoxetine and fluoxetine, selective inhibitors of norepinephrine and serotonin reuptake: are conformational differences an explanation of neurotransmitter selectivity? AB - Low energy conformations and the pathways between them have been calculated for nisoxetine (N-methyl-3-phenyl-3-(o-methoxyphenoxy)-propylamine), (I), a selective inhibitor of neuronal reuptake of norepinephrine, and fluoxetine (N-methyl-3-(p trifluoromethylphenoxy)-3-phenylpropylamine), (II), a selective inhibitor of neuronal reuptake of serotonin. Results are presented as a series of energy maps and ORTEP drawings. Conformational preferences of the protonated forms and preferred conformations in aqueous solution are also established. The CAMSEQ empirical potential method was used throughout. Both the nisoxetine and fluoxetine systems are shown to exhibit the known 'folded-extended' conformational preferences of the phenethylamines. It is suggested that the observed conformational variation between the two systems may play a role in the pharmacological differences between nisoxetine and fluoxetine. PMID- 2908222 TI - Pharmacologic exploitation of neurotransmitter receptors for the design of novel antidepressant drugs. AB - The term 'psychopharmacology' was coined as early as 1920, by David Macht, but it was not until three decades later that the discipline started to develop in a substantial way. The fortuitous discovery of the first antipsychotics and antidepressants, in the 1950s, presented new horizons and gave impetus to the study of drug treatments in psychiatry. In the 1980s, advances in the basic neurosciences, and especially in the characterisation of neurotransmitter receptors, are presenting new opportunities for understanding the biology of mental illness and for designing new drug treatments. This article reviews the evidence linking the action of antidepressant drugs to the regulation of neurotransmitter receptors. We then show how this information has led to a pharmacologic model (melatonin secretion by the human pineal) for the study of antidepressants in depressed patients. Finally, we outline how pharmacologic exploitation of neurotransmitter receptors might lead to new approaches for the design of novel antidepressant drugs. PMID- 2908223 TI - An anomalous effect of N-isopropyl substitution in determining beta-adrenergic activity. AB - We report unexpected results in an investigation of cyclic analogues of dopamine and norepinephrine possessing the structures 1-(aminomethyl)-5,6-dihydroxy 1,2,3,4-tetrahydronaphthalene (3) and 1-(aminomethyl)-5,6-dihydroxy-1,2,3,4 tetrahydro-1-naphthalenol (7). N-Isopropyl substitution of these compounds, providing 4 and 8, brings about the total disappearance of their stimulant activity on beta-adrenergic receptors. On the basis of current knowledge about the structure-activity relationship of adrenergic drugs, it is difficult to provide an explanation for these results; however a tentative rationalization based on conformational considerations is suggested. PMID- 2908224 TI - Molecular orbital studies on the mechanism of drug-receptor interaction. 5. Molecular reactivity and receptor affinity of beta-agonist adrenergic drugs. AB - The electrostatic molecular potential (EMP) of model compounds (isoproterenol and four of its analogs) with agonist activity on the beta-adrenergic receptor was investigated, at the SCF-MO ab initio level. A method was developed to calculate the drug-receptor interaction energy (delta E) for these compounds, and the EMP and delta E values were compared with the affinity of the drugs for the beta adrenergic receptor, quantified in terms of pKd. Our results indicate that the aromatic ring takes part in its entirely in the interaction with the receptor. No particular constituent of the aromatic portion considered by itself appears to play a determining role in this interaction. PMID- 2908225 TI - Structure activity relationships of anxiolytics. AB - Several strikingly different classes of compound bind at the benzodiazepine receptor and exhibit an anxiolytic profile. The conformational preferences of these compounds were ascertained by a variety of techniques. Their electrostatic features were also studied. The combined information has been utilised in the development of a receptor model for the binding site. PMID- 2908226 TI - A Markov process based model of the neurotransmitter-receptor binding process in the brain. AB - A non-deterministic model, based on the assumption that the binding of a neurotransmitter to its receptor is a Markov process, is developed. This model is capable of describing the kinetic processes that occur when a neurotransmitter binds to its receptor under normal and abnormal (pathological) conditions. The model assumes the presence of four states and develops transition probability functions for these states, the expected number of visits to a given state, and the probability of ever reaching a given state. The model explains the probable causes of related disease situations such as Parkinson's disease and schizophrenia, and develops transition probability function and other related statistical properties appropriate to these disease situations. Model parameters of the normal condition were generated by a computer simulation program and compared to those of the pathological conditions. The results of these sample calculations support the assumptions made in the model for normal and disease situations. PMID- 2908227 TI - Synthesis and activity of pyridine analogues of histamine H2-receptor antagonists. AB - Derivatives of 2-amino-3-nitropyridine (4; see Table I for structures) and 2 amino-3-nitro-1H-pyrid-6-one (5), conceived as cyclic 'urea equivalents' of histamine H2-receptor antagonists, were prepared. Pharmacological testing, using the histamine-induced guinea pig atrial chronotropic response, indicated that the R1-pyridyl substituent was a determinant of activity, since the relative activities within an isomeric series were 4-pyridyl greater than 3- and 2 pyridyl. In comparison with analogous 2-amino-3-nitropyridines. (4), 2-amino-3 nitro-1H-pyrid-6-ones (5) had a substantially less histamine H2-receptor antagonist activity. This reduction in activity is attributed to altered orientation of the dipole due to the presence of the C-6 oxo substituent, and/or to the overall effect of oxo in decreasing lipophilicity. The most potent antagonist, 2-[( 2-[(4-pyridyl)methylthio]ethylamino])-3-nitro-6-methoxypyridine, was four times less active than cimetidine. PMID- 2908228 TI - A functional dichotomy in CD4+ T lymphocytes. PMID- 2908229 TI - A functional dichotomy in CD4+ T lymphocytes. PMID- 2908230 TI - Phenotypic and functional heterogeneity of CD4+ T cells. PMID- 2908231 TI - Vitamin K-dependent carboxylation of glutamyl residues in proteins. PMID- 2908232 TI - Functional expression of rat pituitary gonadotrophin-releasing hormone receptors in Xenopus oocytes. AB - Expression of receptors for the hypothalamic regulatory peptide, gonadotrophin releasing hormone (GnRH), was investigated by intracellular recording from Xenopus oocytes injected with poly(A)+ mRNA isolated from rat anterior pituitary glands. Membrane depolarizations were induced in oocytes in a dose-dependent fashion following the application of GnRH (10nM - 1 microM) or a GnRH superactive agonist, buserelin (1nM - 1 microM). The response was reversibly blocked by the addition of a GnRH antagonist (1 microM). TRH (10nM - 1 microM) had no effect on most of these oocytes. In contrast, some other oocytes which showed no responses to GnRH or to the GnRH agonist, displayed depolarizing responses to TRH (10nM - 1 microM). A relatively small number of oocytes responded to both ligands. Control oocytes did not respond to the GnRH analogues or to TRH. This successful expression of the GnRH receptor could provide a new approach to the study of the receptor, and serve as a means for the isolation and cloning of the encoding genes. PMID- 2908233 TI - Actions of pertussis toxin on the inhibitory effects of dopamine and somatostatin on prolactin and growth hormone release from ovine anterior pituitary cells. AB - Forskolin and the phorbol ester 12-O-tetradecanoylphorbol 13-acetate stimulate prolactin and GH release from ovine anterior pituitary cells cultured in vitro. Dopamine and somatostatin inhibit release of prolactin and GH respectively, after stimulation by these agents, but without effects on intracellular cyclic AMP concentrations. In each case the inhibitory effects were reversed by pretreatment of cells with pertussis toxin, in a dose-related fashion (1-100 ng/ml), again without affecting cyclic AMP levels. The results suggest that the inhibitory effects of dopamine and somatostatin in this system are mediated by one or more pertussis toxin-sensitive G proteins, and that these act by a mechanism which does not involve inhibition of adenylate cyclase. PMID- 2908234 TI - Clinical trials of verapamil: comparative studies of verapamil with beta-blockers and nifedipine. PMID- 2908235 TI - A clinical trial of the efficacy and acceptability of D-fenfluramine in the treatment of neuroleptic-induced obesity. AB - Twenty-nine overweight schizophrenic patients maintained on depot neuroleptic injections who wished to lose weight took part in a double-blind, placebo controlled trial of 30 mg D-fenfluramine. All subjects received dietary advice. Sixteen patients completed the 12-week trial. Rate of weight loss was significantly greater in those taking D-fenfluramine. Side-effects were reported, but no deterioration in mental state was noted. PMID- 2908236 TI - Prevalence of obesity in patients receiving depot antipsychotics. AB - Antipsychotic drugs have long been noted to cause pronounced weight gain, and drug-induced obesity can assume major clinical importance in long-term medication in the management of chronic schizophrenia. Obesity is associated with increased morbidity and may reduce compliance, leading to a return of psychotic symptoms. In a survey of 226 patients attending depot neuroleptic clinics in one inner London borough, it was found that the prevalence of clinically relevant obesity was four times that in the general population. PMID- 2908237 TI - Calcium therapy for neuroleptic-induced extrapyramidal symptoms. PMID- 2908238 TI - Aggressive behaviour: evaluation of a non-seclusion policy of a district psychiatric service. AB - An increasing number of psychiatric services have non-seclusion policies. Evaluation of a policy of using specified observation levels instead of seclusion was made over a two-year period. The number of violent incidents recorded in health service facilities was low (exactly 50). Community responses elicited from police, probation, and prison services were not generally critical of the policy. Medication levels used were not excessive as determined by peak levels of major tranquilizer and anti-Parkinsonian drugs used. No patient was excluded from the unit because of his or her level of actual or potential aggression, but two were transferred from it for this reason. PMID- 2908239 TI - The comparative in vitro activity of ofloxacin (RU 43 280) and other quinolone derivatives against 722 bacteria of clinical interest. PMID- 2908240 TI - Antagonization of tetramisole toxicity by hexamethonium. PMID- 2908242 TI - A new diagnostic method for whooping cough. PMID- 2908241 TI - A multiple-center comparative study of the kidney tolerance of ceftazidime versus cefotaxime and tobramycin. PMID- 2908243 TI - [Study on RFLPs of DX13/Bgl II in Chinese and its application on linkage analysis of hemophilia A]. PMID- 2908244 TI - [Cosmetic restoration of anterior teeth. New clinical experiences]. PMID- 2908245 TI - High-voltage electrical injury. PMID- 2908246 TI - Cloning and sequencing of the cyclin-related cdc13+ gene and a cytological study of its role in fission yeast mitosis. AB - We have cloned and sequenced the cdc13+ gene from fission yeast. When a major part of the cdc13+ gene is deleted from the chromosome, cells arrest in interphase, but partial loss of gene activity leads to cells containing condensed chromosomes, aberrant septa and a microtubular cytoskeleton with characteristics of both G2 and M. Expression of this phenotype is influenced by the nutritional status of the cell. Our results suggest that the cdc13+ gene function is required for the control of the G2 to M transition. It appears to play a role in regulating the separate pathways of events involved in the physical process of mitosis, for example in the reorganization of the cytoskeleton on transition from G2 to mitosis. The cdc13+ gene function interacts closely with both the yeast and human homologues of cdc2+, suggesting that mammalian cells may contain a cdc13+ homologue. The gene encodes a putative polypeptide of 482 amino acids, and a central region of 176 amino acids of this polypeptide is 50% identical with sea urchin cyclin. Therefore, the cdc13+ protein is cyclin related and could act as a regulator or substrate of the p34cdc2 protein kinase, which initiates mitosis. PMID- 2908247 TI - The future of lasers in clinical dentistry. PMID- 2908249 TI - Is iprindole an indirect betamimetic drug? AB - Iprindole, an active antidepressant in clinical use, has no effect on norepinephrine reuptake and does not bind to receptors of the noradrenergic system. Iprindole weakly antagonizes reserpine hypothermia and potentiates yohimbine toxicity. This effect is antagonized by propranolol but not by atenolol or metoprolol. In an acute dose, iprindole potentiates the effect of maprotiline on yohimbine toxicity. Beta 2-adrenergic agonists and antagonists specifically modify the effect of iprindole on spontaneous motility. These results indicate that iprindole has an indirect beta 2-mimetic effect. PMID- 2908248 TI - Glutamate receptors of ganglion cells in the rabbit retina: evidence for glutamate as a bipolar cell transmitter. AB - 1. Intracellular and extracellular recordings were obtained from ganglion cells in the rabbit retina. The effects of glutamate analogues and antagonists were studied using a perfusion method for drug application. 2. Kainate (KA) excited all ganglion cells directly and caused a large increase in firing rate. N-Methyl DL-aspartate (NMDLA) also excited ganglion cells but it was less potent and caused burst firing. 3. Quisqualate (QQ) and (RS)-2-amino-3-hydroxy-5-methyl isoxazole-4-propionic acid (AMPA) excited many ganglion cells and were approximately as potent as KA. Less frequently, QQ and AMPA had inhibitory effects possibly due to polysynaptic action. 4. General glutamate antagonists such as cis-2,3-piperidine dicarboxylic acid (PDA) and kynurenic acid blocked the light input to all ganglion cells. PDA and kynurenic acid blocked the effects of KA and NMDLA, but not carbachol, indicating that they act as glutamate antagonists in the rabbit retina. Kynurenic acid did not block the excitatory action of QQ, even though light responses were abolished. 5. Amacrine cells were depolarized by KA or QQ and less potently by NMDLA. Their light-evoked responses were blocked by PDA. 6. We conclude that the light input to ganglion cells in the rabbit retina is predominantly mediated by KA receptors. This is consistent with the idea that 'on' and 'off' bipolar cells are excitatory and release glutamate. PMID- 2908250 TI - Psychophysiological aspects of phobic fears: an evaluative review. AB - The present paper is a review of the use of psychophysiology in diagnosis and treatment of simple phobias. The paper begins with a definition and characterization of phobic fears, together with a description of prevalence rates, age onset, and gender differences. Acquisition is then discussed within a Three-Systems model. Psychophysiological measures are described, and the typical response patterns obtained in phobic reactions are outlined. Special attention is devoted to the paradoxical response seen in blood injury phobias, and the use of beta-blockers and other pharmacological drugs. The paper is ended with a discussion of Lang's emotional imagery as a psychophysiological model for fear reactions and fear therapy. PMID- 2908251 TI - Gas gangrene in a diabetic after intramuscular injection. AB - A 47 year old male insulin-dependent diabetic developed two synchronous life threatening Clostridium perfringens infections under unusual circumstances. Numerous sterile abscesses were also present, being the result of regular pentazocine intramuscular injections. Extensive surgical debridement and parenteral antibiotic therapy proved effective in treating the septicaemia and the large soft tissue abscesses in the buttock and thigh. The patient made an excellent functional recovery. The pathogenesis of gas gangrene after injection is discussed with particular reference to the diabetic patient. PMID- 2908252 TI - Are the neurodevelopmental effects of gonadal hormones related to sex differences in psychiatric illnesses? AB - There are large sex differences in the incidence of many psychiatric diseases. The bases for these sex differences are probably complex and are likely to involve the interaction of both social and biological factors. Probable social factors include child rearing practices, personal expectations and lifestyles, and societal institutions. Biological factors would likely include genetic effects, hormonally mediated neurodevelopmental effects and hormonally mediated neuroregulatory effects. This paper focuses upon the developmental effects of gonadal hormones. The sex differences observed in the neuroanatomy and behavior of nonhuman mammals are reviewed. The instances in which developmental exposure to gonadal hormones has been demonstrated to be involved in establishing these sexual dichotomies are surveyed. The molecular mechanisms by which differences in prenatal and early postnatal levels of gonadal hormones may generate such sex differences are examined. Sex differences in human neuroanatomy and cognitive function are discussed. Finally, we speculate on ways in which similar hormonal mechanisms might act to influence psychiatric disorders. PMID- 2908253 TI - [Evaluation of depressive syndromes on a sectorized basic psychiatric unit]. PMID- 2908254 TI - [Primary, non-pharmacogenic depressions in schizophrenia]. PMID- 2908255 TI - [Students arranged public meeting on suicide in youths]. PMID- 2908256 TI - [Nursing's future is the theme at ICN Congress in 1989]. PMID- 2908257 TI - Kaokoland and its people. PMID- 2908259 TI - [Work Group of European Nurse Researchers, WENR. Report from the 11th meeting and the 4th public conference in Israel]. PMID- 2908258 TI - Tolerability of long-term malaria prophylaxis with the combination mefloquine + sulfadoxine + pyrimethamine (Fansimef): results of a double blind field trial versus chloroquine in Nigeria. AB - A randomized double blind study in long term malaria chemoprophylaxis was performed to compare the tolerability of Fansimef (1 tablet containing 250 mg mefloquine + 500 mg sulfadoxine + 25 mg pyrimethamine per week) with chloroquine (300 mg per week). 211 Austrian industrial workers and their families in Warri, Nigeria, participated in this study; 101 received Fansimef and 110 chloroquine for 3-18 months (mean 41 weeks). Prophylaxis was discontinued because of adverse effects in 7 volunteers in the Fansimef group (mainly insomnia, palpitations, dizziness, nausea and headache) and in 2 volunteers of the chloroquine group (headache and loss of hair in one volunteer, nausea, dizziness and vomiting in the other). Most of the adverse effects could be due to the mefloquine component. A few minor complaints of burning eyes, nausea and gastric pain were reported in both groups. Laboratory checks performed at 3-monthly intervals showed a slight, transient and clinically irrelevant (but statistically significant) increase of serum glutamic-oxalacetic transaminase and gamma-glutamyl transpeptidase at month 3 in the Fansimef group. An attack of acute Plasmodium falciparum malaria occurred in one volunteer 6 weeks after discontinuation of prophylaxis with Fansimef. Antibodies against blood stage parasites could be demonstrated by the indirect immunofluorescence test at different stages of the study, indicating that these two antimalarials are not causal prophylactic agents. PMID- 2908260 TI - [Effects of ginseng root saponins on serum corticosterone and brain neurotransmitters of mice under hypobaric and hypoxic environment]. PMID- 2908261 TI - Cyclin/PCNA is a cell cycle modulated nuclear protein with a role in DNA replication. AB - Cyclin/PCNA (auxiliary protein of DNA polymerase delta) is a proliferation sensitive DNA replication protein whose synthesis is modulated during the cell cycle. All available information suggests that cyclin/PCNA may trigger DNA replication following the formation of pre-replicative complexes at the G1/S transition border. PMID- 2908262 TI - Sequence conservations in vertebrate homeo-box mRNAs. PMID- 2908264 TI - [Evaluation of the effectiveness and tolerance of broxaterol in 10 patients with reversible bronchospasm]. PMID- 2908263 TI - [Azelastine: evaluation of the protective effects in induced bronchospasm challenges]. PMID- 2908265 TI - Continuous monitoring of the movements of erupting and newly erupted teeth of limited growth (ferret mandibular canines) and their responses to hexamethonium. AB - The rates of these eruption-like movements were high and were consistent with reports that eruption is fastest at the time of emergence into the mouth. Once the tooth had attained its initial functional position, there was a significant reduction in the rates. Following administration of the hypotensive agent, hexamethonium, the emerging tooth showed a significant decrease in eruption rates. However, no change was observed for the tooth which had attained its initial functional position. These findings support the view that there are physiological differences at the eruptive and initial functional stages of eruption. The effects of hexamethonium on the erupting ferret canine differ from those reported for the erupting rabbit incisor. This may reflect differences in the eruptive processes for teeth of limited and continuous growth, although other evidence suggests similarities between these. PMID- 2908266 TI - DNA-RFLP analysis and genotyping of HLA-DR and DQ antigens. PMID- 2908267 TI - Can the transgenic expression of Thy-1 reveal its function? PMID- 2908268 TI - Quantitative in-situ hybridization histochemistry studies on growth hormone (GH) gene expression in acromegalic somatotrophs: effects of somatostatin, GH releasing factor and cortisol. AB - We have examined the effects of human GH-releasing factor (1-44) (GRF), cortisol and somatostatin-(1-14) on GH gene expression in solid tissue and dispersed cells from human pituitary adenomas using quantitative in-situ hybridization histochemistry. Sections cut from tissue obtained at hypophysectomy from three acromegalic patients were hybridized to probes directed against mature alpha subunit, GH, prolactin, pro-opiomelanocortin, TSH beta-subunit and LH beta subunit mRNA. Only one biopsy contained GH mRNA in isolation. A second was found to coexhibit GH, prolactin and alpha-subunit mRNA, and a third was found to contain prolactin, TSH beta-subunit, alpha-subunit and LH beta-subunit mRNA, with GH mRNA below the limit of specific detection, indicating that the sample was composed of normal rather than adenomatous pituitary tissue. GH mRNA in individual dispersed cells derived from the latter declined to barely detectable levels over 287 h, both in cultures containing GRF (10 ng/ml) or GRF (10 ng/ml) plus somatostatin (10 ng/ml) and in controls, but increased fourfold in cultures containing GRF (10 ng/ml) plus cortisol (0.5 mumol/l). GH mRNA remained unchanged in both adenoma samples over 138 and 450 h, irrespective of the addition of GRF or GRF plus hydrocortisone. In these samples, somatostatin plus GRF had no consistent effect. These studies confirm that quantitative in-situ hybridization histochemistry can be used to investigate hormone gene regulation in small samples of human tissue and should enable us to define more clearly the level at which abnormal gene regulation occurs. PMID- 2908269 TI - Simultaneous endocardial and epicardial monophasic action potential recordings during brief periods of coronary artery ligation in the dog: influence of adrenaline, beta blockade and alpha blockade. AB - Local differences in the time course of recovery of excitability during the early phase of myocardial ischaemia are important in the genesis of arrhythmias. Catecholamines are known to encourage the formation of arrhythmias and adrenergic blockade is a recognised therapeutic regime. The purpose of this study was to compare the effect of short periods of coronary artery ligation on endocardial and epicardial repolarisation time, to assess any disparity between the two surfaces, and investigate the influence of catecholamines and adrenergic blockade. Simultaneous left ventricular endocardial and epicardial monophasic action potentials (MAPs) were recorded during short periods of left anterior descending coronary artery (LAD) ligation in 9 open chested dogs. Recordings were made during two 90 s periods of LAD ligation. Two further ligations were made during infusion of adrenaline (1 microgram.kg-1.min-1). Subsequently ligations were made after beta blockade with propranolol (0.25 mg.kg-1) and then in the presence of a combination of alpha blockade (phentolamine, 0.15 mg.kg-1) and beta blockade. MAP duration was measured at 90% repolarisation. LAD ligation produced a marked shortening of MAP duration epicardially with only minimal shortening endocardially, which resulted in a highly significant difference between the repolarisation times on the two surfaces. The disparity between surfaces tended to be augmented by adrenaline and was significantly minimised by either beta blockade alone or in combination with alpha blockade. Our results show rapid development of substantial regional differences in repolarisation time between endocardium and epicardium in response to "ischaemia".(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2908270 TI - Extensive fixed drug eruption induced by temazepam. PMID- 2908271 TI - [Evaluation of damage in subjects exposed to nephrotoxic substances]. AB - Nephritic functionality has been studies, making use of same nephritic enzymes dosage (NAG, AAP, alpha-glucosidase, lysozyme) in three groups of workers (varnishers, metallurgists, plastic manufacture employees) professionally exposed to nephritic damage, and in a control group made up of not professionally exposed to the same hazard subjects. The aim was to precociously detect possible nephritic damage, i.e. before classic nephritic functionality indexes were distorted. An increased enzymuria appeared in those subjects that were exposed to nephrotoxic hazard. Increased enzymuria have been found in only one subject of the control group. We deem it should be useful, to customarily measure out nephritic enzymes as trusted index of tabular damage, in hiring and pensionary control examinations. PMID- 2908273 TI - Immunoperoxidase assay for detection of specific IgG and IgA antibodies to human spermatozoa in infertile women. AB - A new immunoperoxidase antibody-membrane antigen (IPAMA) technique for the detection of IgG and IgA antibodies specific for sperm antigens is described. The technique utilizes as antigen sperm cells dried on glass slides and stored at -70 degrees C. Sera of 82 infertile women, 50 primiparas, 50 multiparas and 25 children were tested by IPAMA. Results obtained with the IPAMA test for sperm specific IgG are compared with the results obtained by the sperm immobilization test (SIT). By the IPAMA technique, 11 of 82 infertile women (13.4%) were positive for sperm-specific IgG antibodies, 12 (14.6%) for IgA antibodies and three (3.7%) for both. In the control groups only two of 125 subjects were positive for sperm-specific IgG and none for IgA antibodies. The difference in the prevalence of anti-sperm antibodies between the control groups and the infertility group was highly significant (P less than 0.001). There was agreement between the results of the IPAMA and SIT as to the presence or absence of antibodies in seven of the 11 IgG-positive sera in the infertility group. Four more sera were IgG positive by IPAMA only. The two positive sera in the control group were detected by both IPAMA and SIT. Since the IPAMA technique is simple, does not require special equipment and utilizes stored antigen, it seems that this method could be useful in mass screening of infertile couples. PMID- 2908272 TI - Therapeutic hypogonadism induced by a delayed-release preparation of microcapsules of D-Trp-6-luteinizing hormone-releasing hormone: a preliminary study in eight women with endometriosis. AB - Eight menstrually cycling women with proven endometriosis were treated with a delayed-release preparation of the superactive agonist D-Trp-6-LH-RH in biodegradable microcapsules, administered intramuscularly at intervals of 16 to 36 days for a period of 3 to 5 months. After the first injection which caused a transient stimulatory response, a sustained hypogonadal state, characterized by an estradiol (E2) level less than 50 pg/mL, was induced in all patients by day +14.7 (range 7.19). Subsequent injections caused no more stimulation, but a continuous decrease in E2 levels was observed. In all patients, E2 levels fell to zero after the second or third injection. Gonadotropins remained in the normal range throughout the course of treatment. Hot flashes and severe dyspareunia (related to vaginal dryness) were the main side effects. Resumption of normal pituitary-ovarian activity was documented in all patients after the last injection; the end of the hypogonadal state, ovulation and menses, occurred on days 41 (range 32-59), 58 (range 51-64) and 70 (range 65-76), respectively. All patients showed a clinical improvement. Our results demonstrate that a long lasting, reversible hypogonadism can be induced in cyclic women by intramuscular injections of D-Trp-6-LH-RH microcapsules at monthly intervals. This simple and convenient treatment should be useful in treating endometriosis and other conditions. PMID- 2908274 TI - Changes in sialic acid concentration in human saliva during the menstrual cycle. AB - Salivary sialic acid concentration was studied daily in 20 fertile women during the menstrual cycle. The Warren method was used and plasma LH and BBT were also determined. The sialic acid concentrations in saliva throughout the cycle showed a peak 4 or 5 days before the LH preovulation surge. This maximal peak showed a mean of 10.89 +/- 1.11 mg%. This method may be useful for predicting the pre- and postovulatory fertile period. PMID- 2908275 TI - Reappraisal of the postcoital test: a controlled study. AB - The test results of 34 couples, who were previously infertile, in whom a postcoital test (PCT) was performed during the cycle of conception were compared to the scores obtained in a group of patients with cervical factor only infertility (N = 55). Both the mucus scores and number of motile progressive sperm were significantly (P less than 0.001) higher in the previously infertile group compared to those with the cervical factor infertility. The present study suggests that overall, during the cycle of conception, women have PCT scores which are higher than those with cervical factor infertility. PMID- 2908276 TI - Parity and perinatal mortality amongst diabetics in a Nigerian Teaching Hospital. AB - The parity and the perinatal mortality of 226 married Nigerian female diabetics, aged 20 to 76 years (mean 47.1 years), and 226 married female nondiabetics matched for age and educational level with the diabetics were studied. There was no statistically significant difference between the diabetics and nondiabetics in terms of primary infertility, irrespective of age of onset of diabetes. In the group with one to four deliveries, the nondiabetics significantly outnumbered the diabetics (P less than 0.001) irrespective of age of onset of diabetes. In the group with seven to nine deliveries, only the diabetics of child-bearing age (P less than 0.01); and in the group with 10 or more deliveries, diabetics significantly outnumbered the nondiabetics irrespective of age of onset of diabetes (P less than 0.01). There was a statistically significant difference between the diabetics and nondiabetics in terms of the overall perinatal mortality (P less than 0.001). However, this difference was not significant in diabetics of childbearing age. In Nigeria, where large families are common and children often born in rapid succession, high parity appears not only to increase the chances of a woman developing diabetes in late life but also in early life. Effective birth control practice may thus help in reducing the incidence of diabetes amongst Nigerian women. Additionally, a programme extending to the rural areas aimed at early detection of diabetes and proper management of the pregnant diabetic by a team of medical personnel with special interest in diabetes will help in reducing the perinatal mortality in Nigerian diabetics. PMID- 2908277 TI - Semen biochemistry studies in men with macro-orchidism. AB - Biochemical analysis of semen was performed in six men with bilateral macro orchidism. It has been shown that marker levels of the seminal vesicle secretion (fructose) are higher, whereas marker levels of prostatic secretion (citric acid and calcium) are lower, in these men than in those of a control group of normal men. Whether the pathogenesis of these findings was due to a benign enlargement of the accessory sex glands or not remains to be elucidated. PMID- 2908278 TI - Changes in enzyme levels in human cervical mucus during the menstrual cycle. AB - Cervical mucus is a complex secretion produced by the endocervical epithelium. A comparative analysis of 30 enzymes was carried out on 15 women during their periovulatory period (days 10 to 16 of the menstrual cycle). Nine different enzymes were always found to be present in the cervical mucus. Changes in enzymatic activity were further studied in two of the women, one with a normal (27-day) and the other with a short (20-day) menstrual cycle. The data were compared with those for the same enzymes in the saliva of these two women. Each woman's ovulation time was determined through hormone measurements in urine and blood, as well as by recording basal body temperature and by Billing's method. Our results indicate that a maximum peak occurs for several enzymes during the periovulatory period. PMID- 2908279 TI - Immunoreactive prolactin in breast milk and plasma of women with hyperprolactinemia, galactorrhea and menstrual dysfunction. AB - Prolactin levels were measured by radioimmunoassay in paired breast milk and plasma samples of 11 hyperprolactinemic women with galactorrhea and various menstrual disorders (amenorrhea, n = 8; oligomenorrhea, n = 2; luteal phase defect, n = 1) before and during treatment with bromocriptine (Parlodel, Sandoz). Pretreatment levels of prolactin in the milk and plasma were 80 +/- 13 ng/mL (mean +/- SEM) and 47 +/- 7 ng/mL (P less than 0.05), respectively. While on treatment, the concentration gradient for prolactin remained in favour of the milk, with values for milk and plasma 59 +/- 11 and 29 +/- 3 ng/mL (P less than 0.01), respectively. Thus, bromocriptine lowered the prolactin concentrations in both breast milk and plasma. Since prolactin in milk is biologically active, these findings may be relevant to the initiation and maintenance of lactation in women with abnormal lactogenesis. PMID- 2908280 TI - Reversal of the anti-implantation effect of inhibin with progesterone in the hamster. AB - Inhibin, the gonadal peptide involved in regulation of follicle-stimulating hormone (FSH), exhibited anti-implantation activity in intact and ovariectomized pregnant hamsters. Administration of progesterone reversed the anti-implantation activity of inhibin. Studies were carried out to determine the effect of inhibin on the in vitro synthesis and release of progesterone by the corpora lutea of pregnant hamsters. Inhibin (10 micrograms) was observed to decrease progesterone release by 28%. The administration of exogenous progesterone (2 mg/day) was observed to overcome the anti-implantation effect of inhibin in ovariectomized, pregnant hamsters. These results indicate a possible action of inhibin to interfere with progesterone at the ovarian and/or uterine level in order to exhibit the anti-implantation activity in the hamster. PMID- 2908281 TI - Relative role of different types of aquatic plants in the production of Mansonia. PMID- 2908282 TI - [Introduction to the 17th Retinological Symposium]. PMID- 2908283 TI - Joint US-Sweden workshop: the role of university research in the future development of the biomedical industry. PMID- 2908284 TI - Beta-blockers, lipoproteins and non-insulin dependent diabetes. AB - In a study on 138 hypertensive non-insulin dependent diabetic subjects, factors influencing lipoproteins were assessed. Multiple regression analyses were carried out in order to assess the influence of beta-blocker antihypertensive therapy while making allowances for other confounding variables. In males, but not in females, on a beta-blocker for hypertension, total high density lipoprotein- (HDL ) and HDL-subfraction cholesterol were significantly lower while the serum triglyceride was increased, though not significantly. In male non-insulin dependent diabetics, regimens containing a beta-blocker may worsen an already abnormal lipoprotein profile and antihypertensive agents other than beta-blocking agents should be used if possible. PMID- 2908285 TI - Prevalence and levels of antibodies to the circumsporozoite protein of Plasmodium falciparum in an endemic area and their relationship to resistance against malaria infection. AB - A study on malaria transmission, prevalence of infection and anti-sporozoite antibodies was carried out in Burkina Faso (West Africa). The prevalence and the levels of antibodies to (NANP)3 were found to be related to the entomological sporozoite inoculation rates measured at the same time in a defined area. The major inducer of anti-(NANP)3 antibody production under field conditions is sporozoite inoculation by infected mosquitoes. Levels of antibodies to (NANP)3 vary considerably with age and transmission season. High levels of anti-(NANP)3 antibodies raised under field conditions might offer protection against small inocula of sporozoites. PMID- 2908286 TI - Permethrin-treated bed nets (mosquito nets) prevent malaria in Gambian children. AB - The incidence of clinical attacks of malaria was significantly less in Gambian children aged 1-9 years who slept in villages where all the bed nets (mosquito nets) were treated with permethrin than in children who slept in control villages with placebo-treated nets. Significant differences in changes in spleen size and in packed cell volume were also observed between the 2 groups during the course of a rainy season. No side effect was noted. Treatment of bed nets with insecticide is a form of malaria control that is well suited to community participation and can readily be incorporated into primary health care programmes. Insecticide-treated nets may be more effective in areas of seasonal or low intensity transmission than in areas with heavy perennial challenge. PMID- 2908287 TI - Biological evidence of genetic exchange in Entamoeba histolytica. AB - The demonstration of a new zymodeme of Entamoeba histolytica produced in culture from cloned isolates suggested possible genetic exchange in this parasite. We have attempted to substantiate that finding by using rats as biological hosts. Clones were made from 3 separate isolates of E. histolytica, each established in culture from liver pus or faeces. After enzyme characterization these clones, of zymodemes II, XIV and XIX, were paired in each of the 3 possible combinations and the mixtures injected into the caecum of rats. Clones of new or hybrid zymodemes were produced as well as the original parents, with one exception, the mixture of XIV and XIX, from which only one of the parents was recovered. The hybrids produced included zymodeme XX, observed previously, and zymodeme XI, a naturally occurring zymodeme that has in the past been recovered only from subjects with invasive amoebiasis. PMID- 2908288 TI - An immunological approach to the treatment of inherited life-threatening bone marrow defects. AB - The evidence that the human fetus at 15-22 weeks gestation is still immunoincompetent when judged by the generation of cytotoxic T cell responses is briefly reviewed. It suggests that it might be possible to induce immunological tolerance in the human fetus by the inoculation of allogeneic cells, thus offering a potential treatment for fetuses that have been shown to suffer from life-threatening inherited bone marrow disorders. Adult bone marrow or fetal liver thus transplanted could be expected to establish cellular chimerism and ameliorate the symptoms of the disease. Graft-versus-host disease (GVHD), brought about by mature lymphocytes present in adult bone marrow, poses the main threat. Rodent experiments have shown that GVHD can be avoided if T cell-depleted bone marrow is used in the induction of tolerance. This report summarises experiments in cynomolgus monkeys designed to test this approach rigorously by the inoculation of T-depleted paternal bone marrow cells into fetuses of different ages. Although it has become clear that tolerance can be induced there have been many in utero deaths, at least some of them from GVHD. Those fetuses that went to term were not chimeric. The possible reasons for these disappointing results are discussed. PMID- 2908289 TI - Subdural empyema: a rational management plan. The case against craniotomy. AB - A review of the management of 34 patients with subdural empyema treated at the Derbyshire Royal Infirmary has been undertaken. It is concluded that craniotomy has little part to play in the management of patients with this condition. With modern, improved antimicrobials and prompt burr hole lavage complete recovery should be obtained in the majority of cases. The treatment of the severely ill patient is discussed. PMID- 2908290 TI - Amplification of the epidermal growth factor receptor gene in biopsy specimens from human intracranial tumours. AB - Amplification and overexpression of proto-oncogenes are associated with the malignant nature of some human tumours. In this study we have determined the prevalence of amplification of the proto-oncogenes c-erb B1 (= epidermal growth factor receptor gene), c-erb B2 and c-myc in 44 human intracranial tumours (27 gliomas, six metastases to the brain and 11 meningiomas). None of the tumours had an amplified c-erb B2 gene and only two tumours had an amplified c-myc gene. Nineteen per cent (five out of 27) of the gliomas, 50% (three out of six) of the brain metastases and 0% (0 out of 11) meningiomas had an amplified EGF-receptor gene. Amplification of the EGF-receptor gene appeared to give a growth advantage when single-cell suspensions of the tumours were grown in agarose. PMID- 2908291 TI - Somatostatin 28-immunoreactive inputs to the paraventricular and supraoptic nuclei: principal origin from non-aminergic neurons in the nucleus of the solitary tract. AB - Immunohistochemical and axonal transport methods were used to chart the distribution of somatostatin-immunoreactive (SS-IR) fibres in the paraventricular (PVH) and supraoptic (SO) nuclei of the rat hypothalamus and to identify the cell group(s) from which they originate. Fibres and varicosities immunoreactive for SS 28 and/or SS-281-12 are found primarily in the parvocellular division of the PVH, though aspects of the magnocellular division, and of the SO, in which oxytocinergic neurons are clustered also receive moderate inputs. Combined retrograde transport-immunohistochemical studies indicated that these arise principally from non-catecholaminergic neurons in the lateral aspect of the commissural part of the nucleus of the solitary tract (NTS). SS-28 has been shown to act within the central nervous system to elicit both oxytocin and vasopressin secretory responses, and may be involved in mediating vasopressin secretory responses to haemorrhage. Direct SS-28-IR inputs to the magnocellular cell groups from the NTS, which receives primary visceral sensory inputs, are in a position to play a role in mediating oxytocin secretory responses to interoceptive stimuli; the pathway(s) and mechanism(s) which allow SS-28 to interact with vasopressinergic neurons are not clear. PMID- 2908292 TI - Localization of neuroactive substances in the rat parabigeminal nucleus: an immunohistochemical study. AB - The distribution of neurons and fibres that contain substance P, cholecystokinin 8, vasoactive intestinal polypeptide, corticotropin-releasing factor, calcitonin gene-related peptide, choline acetyltransferase, tyrosine hydroxylase, somatostatin, leucine-enkephalin, and neuropeptide Y was examined in the parabigeminal nucleus of the rat by immunohistochemistry. Many choline acetyltransferase-like immunoreactive or calcitonin-gene-related peptide-like immunoreactive neurons were observed in the dorsal, middle and ventral subdivisions of the parabigeminal nucleus. A few corticotropin-releasing factor like immunoreactive neurons were also seen in these three subdivisions. The double-immunostaining demonstrated that some choline acetyltransferase-like immunoreactive neurons in the dorsal and ventral subdivisions contained calcitonin-gene-related peptide. Fibres containing cholecystokinin-8, substance P or vasoactive intestinal polypeptide were abundant in the parabigeminal nucleus. Fibres containing cholecystokinin-8 were concentrated in the dorsal and ventral subdivisions, and the lateral margin of the middle subdivision, whereas many fibres containing substance P or vasoactive intestinal polypeptide existed in the lateral half of each subdivision. Fibres containing calcitonin-gene-related peptide or corticotropin-releasing factor were mostly observed around the immunoreactive neurons. Tyrosine hydroxylase-like immunoreactive fibres were scattered in the parabigeminal nucleus. PMID- 2908294 TI - Amino acid transport in established adult rat liver epithelial cell lines. AB - The capacities of Na+-dependent transport of alpha-aminoisobutyrate, glutamine and glutamate in four established and three transformed rat liver epithelial cell lines were found to be considerably higher than those of isolated and cultured hepatocytes. At least for transport systems A and G- this seemed to be due to elevated values of Vmax, whereas the values for Km were quite comparable to those of hepatocytes. In contrast to hepatocytes, however, no significant hormonal stimulation of amino acid uptake could be detected in the cell lines. Each normal cell line expressed a distinct pattern of transport capacities with respect to the three systems measured and this was not altered by chemical transformation of the lines. The individual patterns of the lines showed no similarity to presumptive patterns of subpopulations of liver parenchymal cells. In particular, there was no evidence for a direct relationship of one of the cell lines with a small subpopulation of parenchymal cells located adjacent to hepatic venules as revealed by additional measurements of glutamine synthetase, a marker enzyme for this particular subpopulation. It is concluded that established rat liver epithelial cell lines express features characteristic of normal hepatocytes with respect to amino acid transport, but have developed a distinct phenotype adapted to a rapid, hormone-independent growth in vitro. Alteration of their phenotype by transformation is not coupled with a further increase in amino acid transport capacity. PMID- 2908295 TI - Mechanisms of segmentation. Papers presented at a meeting of the British Society for Developmental Biology. Bristol, April 1988. PMID- 2908296 TI - Expression of homeobox gene Hox 1.1 during mouse embryogenesis. AB - Many of the genes controlling segmentation and pattern formation in Drosophila contain a conserved 183 bp sequence known as the homeobox. Homeobox sequences have been found in a range of metazoan species, including the vertebrates mouse and man. This striking conservation suggests that homeobox genes may play a fundamental role in developmental processes. If this is the case then it might be expected that vertebrate homeobox genes will be differentially expressed during embryogenesis and that the timing of their expression will coincide with major morphogenetic events. Here the spatial and temporal patterns of expression of murine homeobox genes will be explored, concentrating on the Hox 1.1 gene as an example. Using in situ hybridization to localize RNA transcripts, it has been found that Hox 1.1 is expressed in a region-specific manner during the formation and differentiation of the embryonic anteroposterior axis. Although striking patterns of expression of Hox 1.1 and other homeobox genes are seen in overtly segmented structures of the embryo (i.e. somites, prevertebral elements, neural tube and dorsal spinal ganglia) expression is also seen in tissues with no obvious segmental origin. The results suggest that homeobox genes probably do not play an exclusive role in segmentation in vertebrates, but are consistent with a role in the assignment of positional identity along the axis of the embryo. PMID- 2908293 TI - Neuronal phosphoproteins. Mediators of signal transduction. AB - This article summarizes some of our knowledge concerning intracellular protein phosphorylation pathways in nerve cells. It also summarizes, very briefly, recent direct experimental evidence involving intracellular injection of protein kinases, protein kinase inhibitors, and substrates, indicating that protein phosphorylation mediates the actions of a variety of neurotransmitters on their target cells. Finally, it summarizes in somewhat greater detail the results of studies of three different types of substrate proteins that appear to regulate different types of biological responses in nerve cells: synapsin I, a substrate protein present in virtually all nerve terminals, which appears to regulate neurotransmitter release from those nerve terminals; the acetylcholine receptor, the phosphorylation of which regulates its rate of desensitization in the presence of acetylcholine; and DARPP-32, the phosphorylation of which converts it into a very potent phosphoprotein phosphatase inhibitor that may be involved in the regulation by the neuromodulator dopamine of the effects of the neurotransmitter glutamate. The identification and characterization of additional neuronal phosphoproteins can be expected to lead to the clarification of numerous additional molecular mechanisms by which signal transduction is carried out in nerve cells. PMID- 2908297 TI - The interaction of proteins encoded by Drosophila homeotic and segmentation genes with specific DNA sequences. AB - The ANT-C gene cluster is part of a network of genes that govern pattern formation in the development of Drosophila. The ANT-C genes encode proteins that contain a conserved 60 amino acid sequence, the homeodomain. Here we show that the homeodomains encoded by two of the ANT-C loci confer sequence-specific DNA binding activity. The DNA sequence specificities of the Dfd and ftz homeodomains appear to overlap completely in vitro, indicating that differences in regulatory specificity among ANT-C and BX-C proteins (assuming that differences exist) must be a consequence of the nonconserved protein sequences found outside of the homeodomains. Deletions that remove sequences from either end of the ftz homeodomain abolish DNA-binding activity, consistent with the commonly held assumption that the homeodomain is a structural domain. The relevance of in vitro DNA-binding experiments to the regulatory function of ftz is supported by our finding that a temperature-sensitive ftz mutation that causes a pairwise fusion of embryonic segments also reduces the affinity of the ftz homeodomain for DNA. Restriction fragments containing ftz homeodomain binding sites were identified within a 90 kb stretch of DNA extending the Antp P1 and P2 promoters. Binding sites appear to be clustered near the P1 promoter but also occur near P2 and in the region between the two. The task remains of determining which of these sequences mediate regulation of Antp by ftz or by other genes that encode closely related homeodomains. PMID- 2908298 TI - Adrenergic receptor effects and antihypertensive actions of beta-adrenoceptor blocking agents with ancillary properties. AB - The acute antihypertensive effects and possible underlying mechanisms of 3 beta adrenergic-blocking drugs with alpha-blocking activity, i.e. labetalol, drugs with alpha-blocking activity, i.e. labetalol, nipradilol and arotinolol, were studied in conscious spontaneously hypertensive rats (SHR) and compared with the effects of prazosin, propranolol and hydralazine. Prazosin produced a dose dependent antihypertensive effect which paralleled inhibition of the pressor response to phenylephrine. Labetalol (30 mg/kg), nipradilol (30 and 100 mg/kg) and arotinolol (30 and 100 mg/kg) also produced a fall in blood pressure. However, inhibition of the pressor response to phenylephrine was not seen in association with the antihypertensive effect after the lower dose of nipradilol and arotinolol. Propranolol (100 mg/kg) did not lower blood pressure. These results suggest that a mechanism(s) other than an alpha-adrenergic-blocking effect plays a role in the acute antihypertensive effects produced by the lower dose of nipradilol and arotinolol. PMID- 2908299 TI - Therapeutic benefits and safety of carvedilol in the treatment of renal hypertension. An open, short term study. Carvedilol Renal Hypertension Study Group in Japan. AB - Carvedilol, a new beta-blocker with vasodilating activity, was given orally to 9 hypertensive inpatients with impaired renal function in a dosage regimen of 5 to 20mg once daily to evaluate its clinical efficacy and safety. Treatment with carvedilol produced a significant decrease in blood pressure from 172/101 to 150/87mm Hg (p less than 0.01), but it did not cause orthostatic hypotension. Heart rate was decreased from 74.3 to 72.8 beats/min, but the decrease was not statistically significant. Serum creatinine and BUN levels were unchanged and other laboratory parameters were within normal limits. There were no side effects in any of the patients during the trial. These results suggest that carvedilol is a useful and safe drug for the treatment of renal hypertension. PMID- 2908300 TI - Influence of carvedilol on blood glucose and glycohaemoglobin A1 in non-insulin dependent diabetics. AB - Pharmacological treatment of hypertension can, cause clinically significant alterations in endocrine function and glucose homeostasis. The aim of this study was to investigate the antihypertensive efficacy and the influence on carbohydrate metabolism of carvedilol and metoprolol in non-insulin-dependent diabetics with mild to moderate hypertension. The patients received either carvedilol 25mg twice daily or metoprolol 50mg twice daily for a period of 4 weeks; if diastolic blood pressure was over 90mm Hg at this time, the dosage was doubled for the subsequent 4 weeks. 49 of 89 enrolled patients completed the trial according to the protocol and were statistically evaluated. After 4 weeks of carvedilol treatment, 23 of 25 patients (92%) showed a good response to therapy (reduction of diastolic blood pressure below 90mm Hg). Doubling of dosage in the carvedilol group did not further increase the response rate after another month of treatment. The response rate after 4 and 8 weeks of metroprolol treatment was 79 and 83%, respectively. In both treatment groups, blood glucose concentrations were maintained within narrow limits. Glycated haemoglobin A1, which provides a profile of the mean blood glucose levels present during the preceding weeks, also remained unchanged. Oral antidiabetic medication taken by the patient remained constant and no hypoglycaemia was reported. When used in therapeutic doses in non-insulin-dependent diabetics, carvedilol is thus unlikely to cause a deterioration of carbohydrate metabolism. PMID- 2908301 TI - Progress in antihypertensive therapy with a multiple-action drug. AB - The beta-blockers in clinical use have been classified into 2 major divisions, nonselective or selective agents, and those with or without intrinsic sympathomimetic activity (ISA). These properties confer differing pharmacological properties with some relevance to the treatment of hypertension. A beta-blocker with significant beta 2-ISA can be regarded as a multiple-action drug. A third division of beta-blockers is a newer development; these agents, besides blocking the beta-receptor, possess important peripheral vasodilator activity. Labetalol was the first drug of this group and prizidolol followed, but has been withdrawn because of toxicity. Several other agents now under evaluation include bucindolol and medroxolol, and carvedilol and dilevalol (1 of the isomers of labetalol), which have been the most widely studied in hypertension. Combined action results in important haemodynamic differences compared with pure beta-blockade. Notably, peripheral resistance is reduced, and there is less reduction in, or no effect on, cardiac output. The 3 following mechanisms have been described as responsible for peripheral vasodilatation: alpha-receptor blockade, beta 2-agonism, and a dilator action independent of either the alpha- or beta-receptors. Evidence for these various mechanisms is more readily obtainable from animal experiments, but some confirmatory evidence has been obtained in man. Inhibition of alpha stimulation has been found with labetalol and to a small degree with medroxalol and carvedilol. beta 2-Mediated vasodilatation has been shown by dilevalol and medroxolol, and evidence of vasodilatation independent of alpha- or beta receptors has been obtained with carvedilol. More evidence is required to confirm the exact contribution of each of these mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2908302 TI - Analysis of the mechanism underlying the vasodilator action of carvedilol in pithed spontaneously hypertensive rats. AB - The present experiments were carried out to examine the vasodilator mechanism(s) of carvedilol by use of pithed spontaneously hypertensive rats (SHR). Animals were pithed and the dose-pressor response curves to various agonists were obtained 0.5 or 1 hour after oral administration of either carvedilol (30 mg/kg), labetalol (60 mg/kg), prazosin (0.1 mg/kg) or hydralazine (3 mg/kg). These doses of drugs caused approximately equihypotensive responses in the conscious state. Carvedilol significantly shifted the dose-pressor response curve to the right for phenylephrine but not for B-HT 920, angiotensin II and vasopressin. Labetalol and prazosin also significantly shifted the dose-response curve to the right for phenylephrine but not for angiotensin II. The rank order of inhibitory action on the phenylephrine response was prazosin greater than labetalol greater than carvedilol. In addition, carvedilol produced a slight but significant inhibition of the pressor responses to serotonin (5-hydroxytryptamine), which was nearly identical in magnitude to that seen with hydralazine. These results suggest that the vasodilator action of carvedilol is mainly attributed to alpha 1-adrenoceptor blockade, although additional non-adrenergic mechanism(s) of action cannot be excluded. PMID- 2908303 TI - Vasodilating mechanism and response to physiological pressor stimuli of acute doses of carvedilol compared with labetalol, propranolol and hydralazine. AB - There is conflicting evidence regarding the main mechanism of the vasodilating effect with carvedilol at therapeutic doses, and to examine this, single doses of carvedilol 50mg and 100mg were compared with labetalol 400mg, propranolol 160mg, propranolol 80mg plus hydralazine 50mg and placebo in healthy subjects. Dose response studies (required to increase heart rate or systolic blood pressure by 25 beats/min and 20mm Hg, respectively) were performed with phenylephrine, angiotensin and isoprenaline after each drug, and placebo administration and the effects of physiological pressor stimuli were compared. Phenylephrine systolic pressure dose-response curves were shifted by labetalol (dose ratio 2.4) and both carvedilol doses (dose ratios 50mg 1.9, 100mg 20.2). The slight shift to the right of the angiotensin dose-response curves with hydralazine plus propranolol (dose ratio 1.4) and carvedilol 50mg (dose ratio 1.4) was not significant. beta Blockade was greatest with propranolol 160mg, followed by carvedilol 100mg, propranolol 80mg plus hydralazine 50mg, carvedilol 50mg and was least with labetalol 400mg (isoprenaline dose ratios required to increase heart rate by 25 beats/min were 55.2, 27.2, 20.2, 14.2, 11.5, respectively). Blood pressure rise with cold pressor and isometric exercise was inhibited most by labetalol. At these acute doses carvedilol displayed some alpha-blockade, but the lower ratio of alpha-blockade to beta-blockade differed from that seen with labetalol, which may account for the different haemodynamic responses at rest and during physiological pressor stimuli with the 2 drugs. There was no definite evidence of direct vasodilator effect. PMID- 2908304 TI - Haemodynamic effects of new beta-blockers with vasodilatory properties in essential hypertension. AB - Six weeks of treatment with carvedilol, N-696, celiprolol, dilevalol, acebutolol, urapidil, doxazosin and altiopril reduced blood pressure with various changes in heart rate. Cardiac index decreased and total peripheral resistance index (TPRI) stayed at the pretreatment levels in the carvedilol, N-696 and acebutolol groups, whereas TPRI tended to decrease in the celiprolol (p less than 0.05), dilevalol (p less than 0.05), urapidil, doxazosin (p less than 0.05) and altiopril groups; cardiac index was unchanged in these groups. As carvedilol and N-696 have no beta 1-selectivity and no intrinsic sympathomimetic activity (ISA), their direct vasodilating property (and the possible alpha-blocking activity of carvedilol) may precipitate in minimising an increase in TPRI induced by vascular beta 2 blockade and suppressed cardiac pump function. Celiprolol and dilevalol, with beta 2-selective ISA, reduced cardiac index slightly and insignificantly, and decreased TPRI. These results indicate that ISA on vascular beta 2-receptors may induce vasodilatation and ISA on cardiac beta 2-receptors may counteract cardiac beta 2-blockade. Differences in haemodynamic responses between these drugs with ISA and vasodilators such as alpha-blocking agents (urapidil and doxazosin) and an ACE inhibitor, altiopril, may be attributable to manifestation of cardiac beta blockade as observed in the drugs with ISA. PMID- 2908305 TI - Dose-effect relationship of carvedilol in essential hypertension. An open study. AB - This study was performed to find the optimal dose of carvedilol, in terms of efficacy and safety, in Japanese patients with mild to moderate essential hypertension. 134 patients with blood pressure greater than 160/95 mm Hg after a 4-week placebo run-in period were initially given carvedilol 5mg once daily. The dose was increased to 10 and 20mg at 4-weekly intervals if the target blood pressure was not achieved. The duration of treatment was 12 weeks. After 12 weeks' administration, the average blood pressure was significantly (p less than 0.001) reduced from 170/101 to 150/91 mm Hg. The hypotensive activity of carvedilol 5mg was mild, but sufficient hypotensive effect was observed in 65% of patients receiving up to 20 mg/day. No significant postural changes in blood pressure were observed. Although heart rate was significantly decreased (77 to 66 beats/min, p less than 0.001), no patient was judged to have bradycardia. Side effects occurred in 5.2% of patients. Carvedilol 10 to 20mg once daily is considered to be an effective and safe treatment for essential hypertension. PMID- 2908306 TI - Effects of carvedilol on blood pressure in patients with mild to moderate hypertension. A dose response study. AB - Carvedilol 12.5, 25 and 50 mg was administered once daily for 4 weeks to patients with mild to moderate hypertension. The purpose of the study was to investigate the antihypertensive action of carvedilol when administered once daily and to investigate the pharmacokinetics of carvedilol in patients with mild to moderate hypertension. Measurable decreases in blood pressure (BP) occurred within 1 hour after the first dose. Peak decreases in supine diastolic blood pressure (DBP) were 9.0 +/- 6.8, 15.5 +/- 6.7, 14.7 +/- 10.6 and 22.5 +/- 7.6mm Hg (+/- SD) for the placebo, 12.5, 25 and 50mg carvedilol groups, respectively, and occurred between 3 and 7 hours after the dose. Administration of carvedilol once daily for 4 weeks kept supine DBP below baseline levels for 24 hours. Trough supine DBP after 4 weeks of treatment were 0.6 +/- 6.5, 7.3 +/- 7.9, 8.8 +/- 7.4 and 12.1 +/ 3.8mm Hg (+/- SD) below baseline. Serum levels of carvedilol were proportional to the dose. Peak serum levels were 39 +/- 27, 75 +/- 38 and 161 +/- 131 mu/L for carvedilol 12.5, 25 and 50mg. The kinetics of carvedilol did not change with repeated administration. Carvedilol was well tolerated; 2 patients experienced dizziness associated with postural hypotension after administration of the 50mg dose. Carvedilol 12.5, 25 and 50mg effectively reduced BP for 24 hours when administered once daily. PMID- 2908308 TI - Dental trauma in contact team sports. PMID- 2908309 TI - Xamoterol in patients with dilated cardiomyopathy: an increase in beta-receptors in lymphocytes. AB - Xamoterol, a partial-beta 1 agonist, was administered orally (100 mg, twice daily) to healthy volunteers (n = 8) and to patients with heart failure (n = 8) for one week. The density (Bmax) and affinity (Kd) of lymphocyte beta-receptors were lower in the patients with heart failure than in the healthy volunteers (Bmax = 931 +/- 214 vs 1466 +/- 373 sites/cell, and Kd = 0.60 +/- 0.11 vs 1.07 +/ 0.14 nM). During treatment with xamoterol, Bmax (7169 +/- 3768 and 7749 +/- 3807 sites/cell) and Kd (6.01 +/- 3.84 and 9.06 +/- 4.66 nM) increased strikingly (p less than 0.01) in both groups. For 12 months, xamoterol (100 mg bd) was given in the same manner to 10 patients with dilated cardiomyopathy. The long-term effects after three and 12 months were assessed. Xamoterol reduced the cardiothoracic ratio from 57 +/- 6% to 55 +/- 5% after three months and 54 +/- 5% after 12 months of treatment (both p less than 0.05), and increased exercise tolerance from 5 +/- 2 min to 7 +/- 2 min and to 7 +/- 2 min (p less than 0.01, p less than 0.05). Echocardiographic fractional shortening increased from 13 +/- 6% to 20 +/- 8% (p less than 0.01) and to 20 +/- 10% (p less than 0.05). Pulmonary wedge pressure during exercise at the same work load decreased from 40 +/- 12 mmHg to 25 +/- 9 mmHg (p less than 0.01) in three months; whereas pulmonary wedge pressures during exercise or at rest in 12 months were unchanged. Exercise heart rate decreased from 118 +/- 9 beats/min to 106 +/- 6 beats/min in three months (p less than 0.01), but was unchanged in 12 months. Bmax and Kd of the beta receptors increased from 1024 +/- 413 sites/cell and 0.67 +/- 0.27 nM to 1976 +/- 497 sites/cell and 1.60 +/- 0.42 nM (both p less than 0.01), respectively, in three months, and 1584 +/- 650 sites/cell (NS) and 1.21 +/- 0.54 nM (p less than 0.05), respectively, in 12 months. It is concluded that xamoterol improves exercise tolerance, hemodynamics and resolves subjective symptoms for certain patients with dilated cardiomyopathy by its actions as a beta-agonist and beta antagonist during longterm treatment. PMID- 2908310 TI - [Ocular symptoms in Takayasu syndrome. I]. PMID- 2908311 TI - [Double-blind study of the effects of sulfasalazine in patients with rheumatoid arthritis]. PMID- 2908307 TI - Response rate with respect to the blood pressure-lowering effect of the vasodilating and beta-blocking agent carvedilol. AB - The aim of this multicentre, double-blind, randomised, controlled study was to evaluate the antihypertensive effect and to determine the response rates, safety and tolerability of 3 doses of carvedilol (25, 50 and 100 mg) compared with those of pindolol 15 mg, in ambulatory patients with mild to moderate uncomplicated essential hypertension. Mean supine diastolic blood pressure was the primary efficacy variable. 205 subjects between 23 and 70 years of age were randomly assigned to receive an oral dose of carvedilol or pindolol once daily for 13 weeks after a placebo run-in period of up to 4 weeks. Before administration of the study medication, blood pressure was recorded at each visit by use of the cuff method, and heart rate was counted. The results showed similar reductions in mean supine diastolic blood pressure among all 4 treatments after 13 weeks. Carvedilol showed a good and similar response rate of approximately 84% at all doses. Heart rate was not significantly changed. The number of patients having adverse experiences possibly related to drug therapy was 4, 16 and 15 with 25, 50 and 100 mg carvediolol, respectively, and 9 with pindolol 15 mg. Dizziness was the most common side effect reported for all medications. In conclusion, carvedilol 25 mg appeared to be the optimum dose in the present study, displaying a high antihypertensive potency with few side effects. PMID- 2908312 TI - The reason for and the pattern of tooth loss in patients treated at Ga-Rankuwa Hospital. PMID- 2908313 TI - Kinetic analyses of transmitter release in neuromuscular transmission. AB - A majority of transmitter quanta in the nerve terminal is in a large pool of store (S), which can be utilized for release only after transformation into activated quanta (n) via two intermediate states called available quanta (A) and releasable quanta (N). Mobilization is a collective term applicable for aggregates of S----A, A----N and N----n conversions. In the present article, various electrophysiological procedures for kinetic analyses of the transmitter release in neuromuscular transmission were discussed to elucidate this not well understood process of mobilization. Especially, frequency augmentation, tetanic rundown and depression, and recovery from depression experiments were proposed to be very useful tools in identifying the drug effect on the mobilization process. Since d-tubocurarine, 2-(4-phenylpiperidino)cyclohexanol (AH5183) and Ba ions satisfied the above three criteria of drug action on mobilization, these were concluded to affect the mobilization of transmitter in neuromuscular transmission. PMID- 2908314 TI - Mitochondrial DNA polymorphism in four Sardinian villages. AB - Polymorphism of mitochondrial DNA has been studied in two highland (Desulo, Tonara) and in two lowland (Galtelli, Orosei) Sardinian isolates, formerly subjected to different selective pressure due to malaria, and in 103 individuals from Northern Italy (Bergamo area), where malaria never appeared to be endemic. Two mitochondrial restriction endonuclease patterns (morphs) never described before have been found, one in the Bergamo and Orosei samples, and the other one only in Orosei. Four new mitochondrial types (mitotypes) due to different combinations of morphs have been identified; two of them have been found only in Sardinia, but with such a low frequency that they cannot be defined as typical Sardinian mitotypes. One mitotype (BamHI-morph 3, MspI-morph 4, AvaII-morph 9 and HaeII-morph 1) showed a significantly higher frequency in the highland rather than in the lowland Sardinian villages or in the Bergamo area. Since this mitotype has been found at a relatively high frequency in Central and Southern Italy, while it has been reported to be rare in Caucasians of Central European origin and absent in other ethnic groups (Africans, Chinese, Japanese and Israeli Jews), we suggest it may represent an ancient Mediterranean type. The analysis of these data suggests that drift or other evolutive forces different from malaria might be the major cause of mitochondrial DNA variation in Sardinia. PMID- 2908315 TI - Enhancement of the autologous mixed lymphocyte reaction (AMLR) in children splenectomized after trauma. AB - Splenectomized individuals have been reported to have many immunological abnormalities. We have studied the proliferative response of T cells in AMLR of nine children who had undergone splenectomy after trauma. T cells from splenectomized patients showed increased proliferative response in AMLR as compared with that observed in parallelly studied controls (38.480 +/- 19.700 vs 11.160 +/- 3.760 dpm). The percentage of CD4 cells was diminished in the group of splenectomized patients. We found strong correlation between AMLR and time after splenectomy (r = -0.81, p less than 0.01). Possible mechanism of elevated AMLR following splenectomy and hypotheses on generation of AMLR are discussed. PMID- 2908316 TI - Multiple endocrine neoplasia. PMID- 2908317 TI - Molecular biology and regulation of the hypothalamic hormones. AB - Over the past twenty years, each of the five major hypothalamic releasing or release-inhibiting hormones has been sequenced and its gene structure determined. With the use of molecular biological techniques, such as in situ hybridization, Northern blot analysis or gene constructs for in vitro or in vivo transfection studies--together with 'traditional' neuroendocrinological techniques, such as immunocytochemistry, radio-immunoassay and portal vessel cannulation- investigators have been able to address major issues in neuroendocrine regulation. Several common themes have emerged: messenger RNA expression is uniformly present in neurons that are immunopositive for the specific hypothalamic hormone. Steady state RNA levels within the hypophysiotropic neuron groups are either increased or reduced by changes in specific target hormones that conform to predictions based on previous physiological data. Regulation by the requisite peripheral hormone is exquisitely anatomically specific and is not evident in extrahypophysiotropic regions. Determining the receptor or genetic basis of this specificity is a major focus of current research. Clarifying the apparently lesser role of afferent neural pathways to the hypothalamus in regulating releasing hormone mRNA levels is also an important challenge. Clinically, the measurement of levels of releasing hormones in the peripheral circulation appears to be of limited usefulness, except in rare cases of ectopic GRH or CRH secretion. For diagnostic purposes, each of the releasing hormones has specific utility in amplifying the release and measurement of pituitary hormones, both to clarify the overall physiological activity of the hypothalamic-pituitary target hormone axis and to further define the anatomic locus of any underlying disturbance. The usefulness of somatostatin as a diagnostic tool is presently limited, but the development of SS receptor antagonists might have significant impact in future clinical investigation. The molecular mechanisms of action of the hypothalamic hormones have been separated into those whose receptor-effector function is mediated by the cAMP-adenylate cyclase pathway(s), GRH and CRH, and those working through the phosphoinositide-protein kinase C cascade, GnRH and TRH. Each of the hormone receptors is coupled to intermediary G proteins, somatostatin uniquely to the inhibitory subclass. The mechanisms responsible for sensitization (priming) or desensitization are not fully understood but are presumably related to receptor down regulation and protein phosphorylation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2908318 TI - The molecular mechanisms of thyroid hormone action. PMID- 2908319 TI - Treatment of subdural empyema. PMID- 2908320 TI - Adhesion-promoting receptors on leukocytes. PMID- 2908321 TI - Do tyrosine hydroxylase-immunoreactive neurons in the ventrolateral arcuate nucleus produce dopamine or only L-dopa? AB - Dopamine (DA) was early demonstrated in the arcuate nucleus by means of the formaldehyde-induced histofluorescence method. In the present study we have investigated the distribution of cell bodies in the arcuate nucleus with antisera against tyrosine hydroxylase (TH), aromatic L-amino acid decarboxylase (AADC) and DA. The results indicate that TH-immunoreactive cells in the dorsomedial part of the arcuate nucleus also contain immunoreactivity for both AADC and DA. However, TH-positive cells in the ventrolateral arcuate nucleus lacked AADC- and DA immunoreactivity with the sensitivity of the present methods. The findings raise the question whether the ventrolateral cells synthesize L-DOPA or DA as endproducts. PMID- 2908322 TI - [Phenotypical curing of Streptococcus pneumoniae treated with amidase induced by the Dp-1 bacteriophage]. AB - A phage-associated murein hydrolase activity (PAL) induced in an autolysis defective mutant of Streptococcus pneumoniae infected with the bacteriophage Dp-1 has been recently isolated and purified to electrophoretic homogeneity as well as biochemically characterized as an endo-N-acetyl-muramyl-L-alanine amidase (1, 3, 4). The PAL and the inactive form (E-form) of the host cell autolysin show a remarkable biochemical similarity, although they differ in their immunological characteristics. The PAL was adsorbed onto a live, defective mutant of pneumococcus (cwl) and such cells reverted to the wild type phenotype ("cured" cells) in some important characteristics present in the wild type strain (R6), as: i) lysis of the culture in the stationary phase, ii) protoplast formation by hypertonic sucrose, and iii) bacteriolytic response against the penicillin in contrast with the bacteriostatic response of the "non-cured" cwl. The adsorbed enzyme segregates during growth of the "cured" cells. Our results demonstrate that PAL acts in the phenotypically "cured" cells in a similar way to that previously described for the host enzyme, and also confirm the finding that the autolysins play a direct role in the irreversible effects produced in S. pneumoniae by the betalactamic antibiotics. PMID- 2908323 TI - [Immunological aspects of Basedow's disease]. PMID- 2908324 TI - [The effects of antihistamines on the histamine content of blood in dogs with thermal injury of the respiratory tract]. PMID- 2908325 TI - Ectopic expression of homeotic genes caused by the elimination of the Polycomb gene in Drosophila imaginal epidermis. AB - The morphological patterns in the adult cuticle of Drosophila are determined principally by the homeotic genes of the bithorax and Antennapedia complexes. We find that many of these genes become indiscriminately active in the adult epidermis when the Pc gene is eliminated. By using the Pc3 mutation and various BX-C mutant combinations, we have generated clones of imaginal cells possessing different combinations of active homeotic genes. We find that, in the absence of BX-C genes, Pc- clones develop prothoracic patterns; this is probably due to the activity of Sex combs reduced which overrules Antennapedia. Adding contributions of Ultrabithorax, abdominal-A and Abdominal-B results in thoracic or abdominal patterns. We have established a hierarchical order among these genes: Antp less than Scr less than Ubx less than abd-A less than Abd-B. In addition, we show that the engrailed gene is ectopically active in Pc- imaginal cells. PMID- 2908326 TI - Pulpal reactions following experimental acute trauma of concussion type on immature dog teeth. PMID- 2908328 TI - Mosquitoes of Daman. PMID- 2908327 TI - [Effect of various beta-adrenolytic drugs and calcium channel blocker (nifedipine) on selected indicators of calcium-phosphorus metabolism in patients with hyperthyroidism and simple goiter]. AB - The study was aimed at evaluation of the effect of short-term treatment with one of the six beta adrenolytic drugs (propranolol, metoprolol, atenolol, pindolol, nadolol, acebutolol) and calcium antagonist nifedipine on the values of several parameters of calcium-phosphorus metabolism in 81 patients with hyperthyroidism (14 patients with Graves' disease, and 67 patients with toxic nodular goiter), and 82 patients with simple goiter. The patients studied have been divided into seven groups, each receiving one of the investigated drugs during four days. A significant decrease in the urinary excretion of hydroxyproline was found only in the patients with hyperthyroidism receiving propranolol. This effect of propranolol on hydroxyprolinuria was not related to the degree of lowering of serum T3 concentration observed in these patients. PMID- 2908329 TI - Evaluation of four azadirachtin rich fractions from neem, Azadirachta indica A. Juss (family: meliaceae) as mosquito larvicides. PMID- 2908330 TI - [Reconstruction of a missing lateral incisor]. PMID- 2908331 TI - Pharmacologic management of behavioral problems in adult dental patients with severe cognitive impairment. PMID- 2908333 TI - Trauma to permanent teeth of children, aged 8, 12 and 15 years, in Ireland. PMID- 2908332 TI - Epidemiological investigation on Japanese encephalitis outbreak in Uttar Pradesh during 1988. PMID- 2908335 TI - Extracellular and membranal bound calcium on the contraction of mesenteric arteries of the rat. PMID- 2908334 TI - [Relevance of urinary enzyme determination for the diagnosis and follow-up of kidney injuries and secondary kidney damage--results of a prospective study]. AB - In a prospective study we examined and confirmed the suitability of urinary enzyme determinations for the diagnosis and control of kidney injuries. Overall, 186 patients were included in the study. 68 patients had blunt lumbar, thoracic and abdominal traumata. Renal operations (n = 14), in particular nephropexy, served as clinical model. Moreover, analyses were performed in 15 polytraumatized patients, 20 patients with fractures of the extremities, 10 patients with thermic injuries, 10 operations on the intervertebral disks, 35 abdominal operations, 1 extirpation of brain tumour, 2 meniscectomies and 11 patients with renal diseases without surgical intervention. We determined the catalytic activities of alanine aminopeptidase (AAP), gamma glutamyltransferase (GGT) and alkaline phosphatase (AP) in the gel-filtered spontaneous urine. The urinary enzyme activities were related to the symptoms, laboratory findings and other parameters. With high sensitivity and without depending on the occurrence and duration of a haematuria the urine enzymes reacted to a traumatic damage to the renal parenchyma by an increased efflux of enzymes. The amount of information from intravenous urography was small. However, there was considerable agreement between nuclear medical findings (isotope nephrography and renal sequence scintigraphy) and enzymuria registered. The methods of investigation complement each other and should be employed in combination. A wide use of urinary enzyme diagnosis to identify mild and moderate renal injuries can be recommended. PMID- 2908336 TI - Biological evaluation of compounds for their physical dependence potential and abuse liability. XII. Drug testing program of the Committee on Problems of Drug Dependence, Inc. (1988). PMID- 2908337 TI - Dependence studies of new compounds in the rhesus monkey, rat and mouse (1988). PMID- 2908339 TI - Fimbriation of Actinobacillus actinomycetemcomitans. PMID- 2908338 TI - Actinobacillus actinomycetemcomitans fimbriae. PMID- 2908340 TI - [A new group of anxiolytic drugs with a mechanism of action different from that of benzodiazepine derivatives]. PMID- 2908341 TI - [Tolerance of classic 1,4-benzodiazepines]. PMID- 2908342 TI - [A new generation of antihistaminics (H1)]. PMID- 2908343 TI - [Features of anterior injured teeth in Zaire]. PMID- 2908344 TI - [Soldering and brazing of orthodontic wires]. PMID- 2908345 TI - [Intralingual ectopic tooth of traumatic origin]. PMID- 2908346 TI - [Treatment of an acute crisis of bronchial asthma in children]. PMID- 2908347 TI - [Bronchial asthma: intercrisis treatment]. PMID- 2908349 TI - Fetal treatment for thyrotoxicosis in non-thyrotoxic pregnant women. AB - Euthyroid or even hypothyroid pregnant women without antithyroid medication but with a history of treatment for thyrotoxicosis, almost always a subtotal strumectomy, may still produce thyroid-stimulating immunoglobulins. This can induce fetal and neonatal thyrotoxicosis. Without treatment this results in a high fetal and neonatal mortality and morbidity. Fetal treatment by administering antithyroid drugs during pregnancy improves this prognosis remarkably. A case is described, the literature is reviewed and guidelines for diagnosis and treatment are presented. PMID- 2908348 TI - [Evaluation and treatment of acute asthma]. PMID- 2908351 TI - T-cell selection in the thymus. AB - Differentiation of early thymocytes into mature T cells depends upon intrathymic T cell contact with major histocompatibility complex (MHC) molecules, i.e., H-2 molecules in mice. T cell recognition of H-2 molecules in the thymus has two consequences. First, some T cells undergo a process of positive selection which leads specifically-reactive immature thymocytes to survive and differentiate into mature functional T cells. Second, T cells with high affinity for H-2 molecules undergo negative selection (tolerance). We and others have argued that positive selection is controlled by thymic epithelial cells, especially cortical epithelium, whereas negative selection reflects contact with bone-marrow (BM) derived cells. This scheme appears to be an oversimplication because we have recently found evidence that a non-BM-derived component of the thymus, presumably epithelial cells, is highly tolerogenic for CD4+ cells. Whether tolerance of CD4+ cells is controlled by cortical epithelium or medullary epithelium is unclear. In this respect it is of interest that chronic injection of mice with cyclosporine A results in selective destruction of medullary epithelial cells and impaired induction of self tolerance. PMID- 2908352 TI - Analysis of CD4 and CD2 receptor function. AB - We have expressed the human CD4 and CD2 molecules in a murine hybridoma, 155.16, that responds to stimulation with human HLA-DR antigens by producing interleukin 2 (IL-2). When stimulated by HLA-DR expressing human cells, the CD4+ and CD2+ hybridomas produce significantly more IL-2 than the parent hybridomas, indicating that CD4 and CD2 are functional. We have used this model system to analyze the role of the CD4 and CD2 surface receptors in T cell activation. Different monoclonal antibodies (mAbs) against CD4 and CD2 were used to define regions of these molecules that may be important for ligand binding and function. Using anti CD4 mAbs in combination with anti-CD3 mAb, and measuring IL-2 production and mobilization of cellular calcium [( Ca2+]i), we have identified two regions of the CD4 molecule that appear to be important for CD4-dependent functions. Anti CD4 mAb Leu3a bound in the first immunoglobulin-like domain and appeared to enhance CD4-dependent functions. mAb OKT4F, which bound in or near the second immunoglobulin-like domain, inhibited CD4-dependent functions. The role of CD2 in T cell activation was analyzed by characterizing hybridomas that expressed wild type and mutated CD2 molecules. This analysis has shown that two regions of the external domain of CD2 are involved in binding of lymphocyte-function associated antigen-3 (LFA-3). Furthermore, binding of CD2 to LFA-3 enhanced T cell activation, and this enhancement was dependent on the cytoplasmic domain of the CD2 molecule. These results suggest that the CD2/LFA-3 interaction provides a stimulatory signal for T cell activation. PMID- 2908353 TI - Immune recognition and effector function in subsets of CD4 T cells. AB - T cells expressing the cell surface differentiation antigen CD4 are involved in most immune responses. Our studies address two issues about CD4 T cell responses to antigen: first, how does the T cell receptor come together with its ligand to generate an immune response, and what is the role of the CD4 molecule in this response? Second, are all CD4 T cells identical in their functional activity, and how does the activating signal determine the functional outcome of a response? Our studies outlined below suggest that the T cell receptor and its peptide: class II major histocompatibility complex (MHC) molecule ligand come together in a defined orientation determined in part by the binding of CD4 to both the T cell receptor and its ligand. Our studies suggest that the V beta chain is involved directly in MHC antigen recognition, binding self MHC with low affinity and non self MHC with high affinity. The selective effect of the Mls locus on V beta expression is believed to reflect the binding of the Mls protein directly to the V beta region. CD4 is described as a co-receptor, forming an inducible part of the T cell receptor and binding to the same class II MHC molecule as that receptor. Studies with both cloned lines and normal CD4 T cell populations suggest the existence of two separable subsets with definable function. One set appears to be specialized for the activation of the humoral immune response, while the other drives the cell-mediated immune responses, particularly those involving the activation of macrophages. These two subsets of CD4 T cells have differential activation requirements, seen particularly in the requirement for interleukin 1 (IL-1) in the activation and clonal expansion of CD4 T cells involved in humoral immunity. This requirement for IL-1 may also be observed in the priming of this subset of CD4 T cells. These studies demonstrate that the optimal activation of CD4+ T cells involves recognition of peptide fragments presented by class II MHC molecules and accessory signals derived from the antigen presenting cells. PMID- 2908354 TI - Immune mechanisms of tissue destruction in vivo. AB - In vivo rejection responses are initiated by specific T cell recognition of foreign histocompatibility antigens expressed by tissue allografts, but it is not certain if the effector mechanism mediating the actual tissue injury is also antigen specific. To directly assess the specificity of the effector phase of in vivo rejection responses, we constructed B6 less than----greater than A/J allophenic mice which are genetic mosaics whose individual cells express either H 2b or H-2a histocompatibility antigens, but not both. Trunk skin from B6 less than----greater than A/J allophenic mice was grafted onto immunoincompetent H-2b nude mice and allowed to heal and regrow hair that was both black and white, reflecting the genetic mosaicism of the allophenic grafts. One month after engraftment, the H-2b nude animals were reconstituted with syngeneic H-2b T cells reactive against H-2a allodeterminants. An obvious rejection response ensued involving antigen-nonspecific inflammatory destruction of the epidermis and complete hair loss. Despite the intensity of the nonspecific inflammatory response, the allophenic skin grafts survived Importantly, the allophenic grafts regrew hair and the predominant color of that hair was black, providing visual proof that syngeneic B6 melanocytes and hair follicle cells had not been destroyed. Thus, destruction of skin allografts is mediated by antigen specific effector T cells that assess individual cells within the dermis of the graft for expression of foreign histocompatibility antigens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2908355 TI - The role of the neu oncogene product in cell transformation and normal development. AB - p185neu, the protein product of the neu gene, is a tyrosine kinase receptor with structural similarity to the epidermal growth factor (EGF) receptor. The cognate ligand for the p185neu receptor remains unknown. We have defined: 1) stage and tissue-specific expression patterns of the neu gene product in developing tissues; 2) p185neu phosphorylation and the regulation of p185neu tyrosine kinase activity by EGF. 3) Synergistic interactions of cellular rat p185neu and EGF receptor leading to cell transformation; 4) structural and functional differences of normal and oncogenic p185neu. These observations explain some features of how p185neu is involved in normal development and neoplastic transformation. PMID- 2908356 TI - Correlation between toxin formation and diarrhoea in patients infected with Aeromonas. PMID- 2908357 TI - Comparison of four typing methods for Aeromonas species. PMID- 2908358 TI - [Traumatic injuries of the teeth]. PMID- 2908359 TI - [The measurements of somatostatin by radioimmunoassay]. PMID- 2908360 TI - [The development of a radioimmunoassay for somatostatin]. PMID- 2908361 TI - [Asthma patients: oral sequelae of adrenergic agonists]. PMID- 2908362 TI - A new sensitive method which unlike the Vogel test detects the anxiolytic effect of tofisopam. AB - A new, more sensitive than previously used anxiolytic test is described. The test consists in measuring of inhibition by punishment of drinking water necessary to swallow dry food by very hungry rats. This test reveals the anxiolytic properties of tofisopam, a clinically effective benzodiazepine anxiolytic, and of very low doses of chlordiazepoxide, both ineffective in the Vogel test, as well as anxiolytic properties of high doses of chlordiazepoxide and other anxiolytics, and confirms the lack of anxiolytic effects of major tranquilizers. The results suggest that chlordiazepoxide (and possibly other benzodiazepines) acts on two subgroups of benzodiazepine receptors, named BRI (high affinity) and BR2 (low affinity), while tofisopam acts specifically on BRI receptors. The new test is proposed as a tool for a search for drugs specifically acting on high affinity benzodiazepine BRI receptors. PMID- 2908363 TI - Substituted ergolines: potential antipsychotics with unique profile. I. Psychopharmacological characterization. AB - Different ergot structures (lumilysergol and lysergol) were chlorinated or brominated in the position 2, and the development of antidopaminergic activity was studied. The tested 2-halo-lysergols exerted neuroleptic-like action indicated by the suppression of conditioned avoidance response (CAR), and other effects characteristic of dopamine antagonists (cataleptogenic effect, prevention of amphetamine-induced toxicity, inhibition of L-DOPA-induced hyperactivity, lowering of spontaneous body temperature, antagonism of apomorphine-induced hypothermia). A second halogen substitution in the position 8 of the lysergol structure left the CAR suppression activity untouched, but abolished other dopamine antagonistic effects. This unique psychopharmacological profile refers to potential usefulness of the compounds in schizophrenia, and at the same time perhaps in particular forms of Parkinson's disease or tardive dyskinesia. PMID- 2908364 TI - EGYT-2509 a novel neuroleptic agent without extrapyramidal and endocrine side effects. AB - The dibenzodioxazocine derivative EGYT-2509 was effective in neuropsychopharmacological tests characteristic for neuroleptics and antiparkinsonian drugs. It interacted with dopaminergic compounds similarly to chlorpromazine and haloperidol, but in certain tests it showed different activity. Similarly to chlorpromazine and haloperidol it inhibited the lethal effect of amphetamine in grouped mice. The apomorphine-induced stereotypy was potentiated by lower, and antagonized by higher doses of EGYT-2509. The compound did not show cataleptogenic activity and even antagonized the catalepsy evoked by bulbocapnine. The in vitro potency of EGYT-2509 to block dopamine-mediated inhibition of prolactin release was weaker by three orders of magnitude than that of haloperidol. In preliminary human studies it did not affect the plasma prolactin level. It is concluded that EGYT-2509 is a new potential antipsychotic agent with minimal risk of extrapyramidal and endocrine side effects. PMID- 2908365 TI - Heterogeneity of presynaptic muscarinic receptors located on different tissue preparations. AB - Three different tissue preparations were used to demonstrate the heterogeneity of presynaptic muscarinic receptors that modulate neurotransmitter release. The presynaptic antimuscarinic potency of several muscarinic antagonists was characterized with the enhancement of the neurotransmitter release evoked by electrical stimulation on the guinea-pig ileum Auerbach plexus, the guinea-pig atrium and the rat brain cortex. Presynaptic muscarinic receptors located on the Auerbach plexus proved to be different of those present on the cortical cholinergic interneurons and on the sympathetic plexus of the guinea-pig atrium. PMID- 2908366 TI - The effect of (-) deprenyl (selegiline) on different behavioral changes induced by dopamine agonists in the rat. AB - The effect of (-) deprenyl was investigated both on the stereotyped behavior and on other types of activities induced by various dopamine (DA) agonists. (-) Deprenyl was given in a single dose, 1 h prior to the DA agonists. 1-2 mg/kg sc ( ) deprenyl decreased the stereotypy induced by amphetamine (AMPH, 2.5 mg/kg sc), but 20 mg/kg was needed to reduce the stereotypy-inducing effect of apomorphine (APO, 0.3 mg/kg sc). The stereotypy-inducing effect of phenyl-ethyl-amine (PEA, 40 mg/kg sc) was significantly enhanced by 0.25 mg/kg sc (-) deprenyl pretreatment. The PEA or AMPH-induced increase in the horizontal activity (locomotion) and the vertical activity (rearing) remained unchanged after a single dose of (-) deprenyl, showing that this drug acts primarily on the nigro striatal dopaminergic system. PMID- 2908367 TI - Berbanes: search for novel alpha-2 adrenoceptor antagonists. AB - We have previously described the alpha-2 adrenoceptor antagonist properties of berbanes and its stereoisomers. Of the compounds studied CH-38083 (2,3 methylenedioxy-11-betahydroxyalloberbane) has been selected for further analysis based upon its high affinity and selectivity for central and peripheral alpha-2 adrenoceptors. Structure activity relationship study revealed that the aromatic ring with its substituents at C-2 and C-3 positions, the nitrogen atom, the hydroxy group at C-11 position and the methoxycarbonyl group at C-12 position are important for the binding of the berbanes to the alpha-2 adrenoceptors. Using alloberbane derivatives for characterization of the alpha-2 adrenoceptors it was speculated that xylazine sensitive alpha-2 adrenoceptors in the rat vas deferens and in the guinea-pig ileum are similar, whereas xylazine sensitive and noradrenaline sensitive alpha-2 adrenoceptors of the guinea-pig ileum may belong to different subtypes. Correlation studies indicated that modification of the molecular structure of the alloberbanes can lead to either increased or decreased alpha-2 adrenoceptor antagonists activity without parallel changes in the alpha-1 adrenoceptor antagonist potency. The low affinity of CH-38083 for other receptor populations (muscarinic, histamine, dopamine receptors) makes this compound attractive for investigation of alpha-2 adrenoceptor-mediated neural processes in the central nervous system and periphery. PMID- 2908368 TI - [Immunoenzyme methods in the epidemiology, diagnosis and experimental study of hemorrhagic fever with renal syndrome]. PMID- 2908369 TI - The George M. Kober lecture. Basic immunology: the path to the delineation of the immunopathogenic mechanisms of HIV infection. PMID- 2908370 TI - Comparison of the insulin receptor gene and insulin binding in families with severe insulin resistance. PMID- 2908371 TI - Molecular genetics of the human beta-spectrin gene. PMID- 2908373 TI - Management of trauma to the primary dentition. PMID- 2908372 TI - The enzymatic correlate for the renal adaptation to chronic metabolic acidosis and metabolic alkalosis in rat nephron. PMID- 2908375 TI - [Traumatic injuries to the teeth in children]. PMID- 2908374 TI - [Pathophysiologic mechanisms of myocardial ischemia and an approach to drug therapy in patients]. PMID- 2908376 TI - [Alternative copper-aluminum alloys. Study of traction resistance. Effect of alloys on soldering]. PMID- 2908377 TI - [Duration of the therapeutic effect of a beta 2 stimulant (procaterol hydrochloride) in patients with asthmatiform bronchopathies]. PMID- 2908378 TI - [Protective action of broxaterol in bronchial spasm induced by ultrasonic mist]. PMID- 2908380 TI - Structure of suriclone, a benzodiazepine receptor agonist. AB - 6-(7-Chloro-1,8-naphthyridin-2-yl)-2,3,6,7-tetrahydro-4-methyl-7- oxo-5H-1,4 dithiino[2,3-c]-pyrrol-5-yl-1-piperazinecarboxylic++ + acid, C20H20C1N5-O3S2, Mr = 477.9, triclinic, P1, a = 8.7066 (3), b = 9.7665 (8), c = 14.2515 (16) A, alpha = 80.986 (9), beta = 75.168 (6), gamma = 65.884 (5) degrees, V = 1067.4 (2) A3, Z = 2, F(000) = 496, room temperature, Dm = 1.482, D chi = 1.487 g cm-3, lambda(Cu K alpha) = 1.54178 A, Ni filter, mu = 36.3 cm-1, R = 0.053, omega R = 0.070 for the 3538 reflections included in the refinement. Comparisons of the structures of the two enantiomers of suriclone and the active conformer of the 1,4 benzodiazepine anxiolytics allow the identification of the active form of suriclone as the R isomer. PMID- 2908379 TI - The molecular biology of pattern formation in the early embryonic development of Drosophila. PMID- 2908381 TI - Research on parasitic arthropods of the Lake Zarnowieckie environs carried out in 1981-1985. Part II. Mosquitoes (Diptera, Culicidae). AB - In the years 1981-1985 a total of 19,651 specimens mosquitoes were collected in the area of investigation--Lake Zarnowieckie environs. In that amount 15,072 specimens were identified. There were found 26 species belonging to 4 genera: Anopheles, Aedes, Culex and Culiseta. Some of the species found, such as Aedes cantans, Aedes punctor or Culex pipiens are troublesome pests and particularly aggressive to man, possible vectors of many diseases. In the cowsheds there were found 12 species, the most numerous were the specimens of Anopheles genera (92.1% of the collection). The species captured in the open area by means of the man bait were 17 in number. The highest aggressiveness to man was shown by Ae. punctor, Ae. cinereus, Ae. cantans and Ae. annulipes. In the water bodies among the preimaginal forms caught there identified were 22 species. The majority of them were: Culex pipiens and Aedes punctor. A seasonal activity of the Culicidae preimaginal forms was also observed. The considerable environmental changes caused by the construction of the nuclear power plant, and the work of the pump storage power plant are, as it seems, the main cause of the changes in the species domination observed in this region. Any finau conclusions, however, can be drawn after the further investigations are completed. PMID- 2908382 TI - [A histochemical study of the APUD cells in oral region on experimentally induced zinc-deficient mice, with special reference to the taste buds and the mast cells]. PMID- 2908383 TI - [Chronic Jaccoud polyarthritis and Takayasu arteritis]. PMID- 2908384 TI - [Alcohol and the central nervous system--fundamental neurochemical aspects of alcohol dependence]. PMID- 2908385 TI - [Molecular analysis of alpha-4 globin pseudogene polymorphism in mice]. PMID- 2908386 TI - [Neuropeptides and neoplasms]. PMID- 2908387 TI - [Successful autologous transplantation of circulating hematopoietic stem cells in acute myeloblastic leukemia]. PMID- 2908388 TI - [Protein C and protein S abnormalities]. PMID- 2908389 TI - [Genetic aspects of muscular dystrophy]. PMID- 2908390 TI - [Genetic aspects of Huntington's chorea]. PMID- 2908391 TI - [Genetic aspects of fragile X syndrome]. PMID- 2908392 TI - [DNA diagnosis of inborn errors of metabolism]. PMID- 2908393 TI - [Pedigree analysis on micro genetics]. PMID- 2908394 TI - [Phenylketonuria]. PMID- 2908395 TI - [Ornithine transcarbamylase deficiency]. PMID- 2908396 TI - [Argininemia (arginase deficiency)]. PMID- 2908397 TI - [Methylmalonic acidemia]. PMID- 2908398 TI - [Adenine phosphoribosyltransferase deficiency]. PMID- 2908399 TI - [Glucocerebrosidase deficiency--Gaucher's disease]. PMID- 2908400 TI - [Arylsulfatase A deficiency-metachromatic leukodystrophy]. PMID- 2908401 TI - [Genetic mutants of apolipoproteins and abnormalities of lipoprotein metabolism]. PMID- 2908402 TI - [Human growth hormone gene deletion]. PMID- 2908403 TI - [Multiple endocrine neoplasia type 2: mapping of the gene predisposing and alteration of genotypes in tumor]. PMID- 2908404 TI - [Molecular genetics of hemophilia B and vitamin K-dependent proteins]. PMID- 2908405 TI - Tolerance to the anticonvulsant effect of benzodiazepines. PMID- 2908406 TI - Multiple B2 kinin receptors in mammalian tissues. PMID- 2908407 TI - Fimbriae from the oral anaerobe Bacteroides gingivalis: a screening of clinical isolates from various places. PMID- 2908408 TI - Formation of the vertebrate neuromuscular junction. AB - The sequence of events leading to the formation of the NMJ based on the data presented in this chapter from rat, chick, and Xenopus muscle can be divided into three developmental stages, as shown in Table I. The essential components of the NMJ are acquired early. Acetylcholine is present and can be released from the growing nerve. Acetylcholine receptors are present in the muscle membrane and are functional even at the earliest times. These components of the junction--ACh release and functional ACh receptors--can develop independently of each other; i.e., cell culture studies have shown that nerve cells are capable of releasing ACh before their growing tips have come into contact with the postsynaptic muscle membrane. Conversely, muscle cells grown without nerve synthesize and incorporate in their membranes functional ACh receptors. This situation ensures that functional (table; see text) contacts can occur even at the earliest times. Local accumulation of ACh receptors is also detected at the earliest times of junction formation. Although cell culture studies have demonstrated that receptors can aggregate in the absence of nerve, it would appear that the nerve plays an important role in directing where the highest density of receptors will be localized. Acetylcholinesterase, identified both histochemically and electrophysiologically, occurs at the presumptive NMJ shortly after synaptic transmission and receptor clustering have begun, suggesting that these events may play a role in localizing cholinesterase. Although the studies on rat and chick muscle support this view, development of AChE on Xenopus muscle does not require prior exposure to nerve or muscle activity. The ultrastructural features characteristic of the adult NMJ also do not become apparent until after synaptic transmission and receptor clustering have been seen. However, detection of small regions of specialization could be easily overlooked at the ultrastructural level, particularly if the tissue has not been serially sectioned. The young tissue is more fragile (Gordon et al., 1974) and may be more susceptible to mechanical damage or alterations from the fixation procedures (Kullberg et al., 1977). For these reasons, results pertaining to when the ultrastructural specializations occur are difficult to interpret and must await identification of these structures by other means. A number of other changes occur at the NMJ late in development: (1) ACh receptors become metabolically more stable, (2) there is a conversion in the kinetics of the ACh receptor channel, and (3) junctional folds become apparent. The extent to which these changes occur varies among the different organisms discussed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2908409 TI - A study of central neurotransmitter mechanisms in morphine-induced 'Straub reaction' in mice: role of central dopamine receptors. AB - 1. The role of putative neurotransmitters was investigated in morphine-induced Straub reaction (SR) in albino mice. 2. Apomorphine (15 mg/kg) was also effective in inducing SR. However, in a smaller dose (0.2 mg/kg) it blocked SR induced by morphine. 3. Morphine-induced SR was potentiated by tranylcypromine, reserpine (acute effect), imipramine and L-dopa and blocked by reserpine (chronic effect), alpha-methyldopa, pimozide, chlorpromazine, haloperidol and metoclopramide. Prazosin and clonidine partially blocked morphine SR in high doses. 4. Propranolol, yohimbine, cyproheptadine and atropine were ineffective in blocking morphine SR. 5. The results indicate that morphine SR is mediated through release of DA in the CNS which excites central D2 receptors. Activation of central alpha 1-adrenoceptors might also play a minor role. PMID- 2908410 TI - Rilmenidine acts as a partial agonist at prejunctional alpha 2-adrenoceptors in guinea-pig atria. AB - 1. The present study was carried out to determine whether rilmenidine, a recently introduced antihypertensive agent which acts on alpha 2-adrenoceptors, has partial agonist activity on prejunctional alpha 2-adrenoceptors in guinea-pig atria. 2. Isolated preparations of guinea-pig atria were incubated with [3H] noradrenaline and the efflux of radioactivity induced by stimulation of intramural sympathetic nerves was used as an index of release of transmitter noradrenaline. 3. Rilmenidine (1 mumol/l) inhibited noradrenaline release evoked by short trains (five, 20 and 50 pulses) of sympathetic nerve stimulation and this inhibitory effect of rilmenidine was antagonized by the alpha 2-adrenoceptor antagonists, idazoxan (0.1 and 0.3 mumol/l) and rauwolscine (0.3 mumol/l) whereas it was not affected by the alpha 1-adrenoceptor antagonist prazosin (0.1 mumol/l). 4. On the other hand, rilmenidine (1 mumol/l) enhanced noradrenaline release evoked by long trains (150 and 300 pulses) of stimulation and this effect was also abolished by idazoxan (0.1 mumol/l). 5. These findings suggest that the effects of rilmenidine on transmitter release depend on the degree of auto inhibition: when the concentration of noradrenaline in the biophase of the prejunctional alpha 2-adrenoceptors is low, rilmenidine acts as an agonist, but when the concentration is high it acts as an antagonist. Thus, rilmenidine, like clonidine, is a partial agonist on prejunctional alpha 2-adrenoceptors in guinea pig atria. PMID- 2908411 TI - AIDS: interim guidelines. PMID- 2908412 TI - Handling the HTLV-III antibody positive blood donor. PMID- 2908413 TI - Schoolchildren and AIDS. PMID- 2908414 TI - The doctor's duty towards AIDS patients. PMID- 2908415 TI - AIDS and medical ethics. PMID- 2908416 TI - [Growing Clostridium on nutritional media with polyacrylamide gel]. PMID- 2908417 TI - [Clinical significance of changes in the number and function of adrenergic receptors]. PMID- 2908418 TI - [Progress in endocrinology]. PMID- 2908419 TI - [Flumazepil (Anexate) in the treatment of acute benzodiazepine poisoning. Preliminary report]. PMID- 2908420 TI - [Benzodiazepine receptor in the central nervous system and its natural and synthetic agonists and antagonists. Clinical uses]. PMID- 2908421 TI - [Self-regulation of nerve function]. PMID- 2908422 TI - [Gamma-glutamyltranspeptidase in newborn infants]. PMID- 2908423 TI - Insulin affects glucose uptake by muscle and mammary tissues of lactating ewes. AB - Effects of insulin on exchanges of glucose across skeletal muscle and mammary tissue were measured in short-term studies in lactating ewes. Insulin secretion was suppressed by a primed/continuous infusion of somatostatin, then insulin was administered by continuous intravenous infusion of doses that were increased, in a step-wise manner, from 0 to 2 U h-1. Plasma glucose was maintained essentially constant by frequent monitoring and intravenous administration of exogenous glucose. Somatostatin suppressed but did not completely inhibit insulin secretion as shown by maintenance of plasma concentration of C-peptide. As plasma insulin was increased, while arterial glucose was maintained stable, uptake of glucose by skeletal muscle increased and glucose uptake by the mammary gland decreased. These observations confirm the role of insulin in regulating glucose uptake by skeletal muscle and raise the possibility that insulin also regulates glucose uptake by the mammary gland. PMID- 2908424 TI - Effects of lys-beta-urogastrone in vivo. AB - Lys-beta-urogastrone, an analogue of human beta-urogastrone with an additional N terminal lysine, was shown to have similar effects in mice and sheep to mouse epidermal growth factor (mEGF). Lys-beta-urogastrone in doses of 0.18-3.24 micrograms g-1 body weight caused both precocious separation of eyelids and eruption of incisors in neonatal mice. In 17 sheep, intravenous infusion of the urogastrone analogue over c. 24 h led, towards the end of infusion, to erythema of the muzzle, caused reductions in voluntary food intake (with doses greater than or equal to 50 micrograms kg-1) and generally easier manual harvesting of the fleece (with infusions greater than or equal to 81 micrograms kg-1), with spontaneous shedding of the fleece (c. 14 days after infusions of greater than or equal to 116 micrograms kg-1). In five sheep infusions of 25, 38, 50, 83 and 118 micrograms kg-1 fleece-free body weight, plasma concentrations of lys-beta urogastrone were near maximal 20 h after the infusions started and were, respectively, 1.1, 1.7, 5.5, 18 and 79 micrograms l-1 plasma. Plasma concentrations of gastrin, somatostatin and pancreatic polypeptide were determined in these five sheep. Plasma gastrin rose sixfold by the end of infusions of 25 micrograms kg-1 of the urogastrone analogue, and tenfold with the higher doses of infusion. Although plasma somatostatin concentrations were variable, a consistent trend was observed; lower levels were apparent during the lys-beta-urogastrone infusions. There was no discernible trend in pancreatic polypeptide concentrations. PMID- 2908425 TI - Structure and dynamics of double helices in solution: modes of DNA bending. AB - The long range structure of DNA restriction fragments has been analysed by electro-optical measurements. The overall rotation time constants observed in a low salt buffer with monovalent ions is shown to decrease upon addition of Mg2+ or spermine. Since the circular dichroism and also the limiting value of the linear dichroism remain almost constant under these conditions, the effect is attributed to a change of the long range structure. According to a weakly bending rod model, the persistence length decreases from about 600 A in the absence of Mg2+ or spermine to about 350 A in the presence of these ions. The persistence length measured in the presence of Mg2+ is almost independent of temperature in the range of 10 to 40 degrees C. The nature of DNA bending is analysed by measurements of bending amplitudes and time constants from dichroism decay curves. The observed absence of changes in the bending amplitudes upon addition of Mg2+ or spermine, even though addition induces changes of the persistence length by a factor of 2, is hardly consistent with simple thermal bending. The combined results, including the remarkably small temperature dependence of persistence length and bending amplitude, can be explained by the existence of two bending effects: inherent curvature of DNA dominates at low temperature, whereas thermal bending prevails at high temperature. Analysis of bending amplitudes from dichroism decay curves according to an arc model provides an approximate measure for the degree of bending in restriction fragments. The model is consistent with the observed chain length dependence of bending amplitudes and provides an approximate curvature corresponding to a radius of about 400 A. Thus the curvature observed in restriction fragments is similar to that observed for high molecular DNA condensed into toroids by addition of ions like spermine. Particularly strong bending of DNA is induced by [Co(NH3)6]3+, indicated by an apparent persistence length of 200 A and an increased bending amplitude together with a reduced limit value of the linear dichroism. This effect is attributed to the high charge density of this ion and potential site binding. PMID- 2908426 TI - CC/GG contacts facilitate the B to A transition of DNA in solution. AB - Self-complementary decadeoxynucleotides, CCGATATCGG, CCAGATCTGG, CCCTGCAGGG, GGGGGCCCCC, were designed and synthesized to estimate the A-philic free energy of CC/GG contacts. First, regions of temperature-stability of the double-stranded conformation were determined for each 10-mer. Then, circular dichroism spectra were recorded for the B-family forms at different temperatures, counter-ion concentrations and trifluoroethanol contents. A cooperative change typical of the B-A transition is observed in the CD spectra at a trifluoroethanol content specific for each duplex. The positions of half-transition points were functions not only of the nucleotide sequence but of the duplex length as well: the B to A transitions were hindered in these 10-mers in comparison with a lengthy DNA. The B-phility value was estimated to be 3 kcal/mol of 10-mer. The B-A transition point was shown to drop with an increase in the number of CC/GG contacts in a duplex. The designed 10-mers made it possible to estimate quantitatively the A phility of CC/GG contact as compared with an average DNA: (FA-FB)CC = 0.2 Kcal/mol, (FA-FB)DNA = 0.7 Kcal/mol. PMID- 2908427 TI - Physical mechanism of ATP formation in biomembranes. AB - Membrane-bound and isolated H+ ATPases of various origin are able to synthesize ATP from ADP and Pi after a jump-like pH increase. In the course of this increase the pH of solution (or suspension) must cross a value corresponding to pK of certain acid groups in the catalytic component of ATPase. In the case of isolated soluble enzymes it is possible to obtain up to 10 ATP molecules per one pH jump per one enzyme molecule. A physical mechanism of this phenomenon as well as of oxidative and photosynthetic phosphorylation is suggested. PMID- 2908428 TI - Structure of the ABC ring synthon of dendrobine. AB - (1R,4S,8S,11R)-11-Methyl-3-[(R)-alpha-phenyl-ethyl]-3- azatricyclo[6.2.1.0(4.11)]undec-5-en-2-one, C19H23NO, Mr = 281.40, orthorhombic, P2(1)2(1)2(1), a = 9.534 (2), b = 11.055 (4), C = 14.372 (4) A, V = 1514.8 (8) A, Z = 4, Dx = 1.23 (163 K), Dm = 1.15 g cm-3 (295 K), lambda(Mo K alpha) = 0.71069 A, mu = 0.702 cm-1, F(000) = 608, T = 163 K, R = 0.0387 for 2310 reflections. The absolute configuration is assigned on the basis of internal comparison with the alpha-methylbenzylamine moiety. The tricyclic ring system is concave. The N appears to be sp2 hybridized [N is 0.0661 (1) A from the plane through C atoms bound to it] and conjugated through the carbonyl group [short C-N bond [1.351 (2) A]]. Ring strain appears to cause a slight increase in the C-C bond lengths of the center atom of the tricyclic ring system. The average bond length from this atom to the three other ring C atoms is 1.557 (1) A while the average bond length for all other sp3-C to sp3-C bonds is 1.529 (1) A. PMID- 2908429 TI - [Endodontic solutions to extensive periapical radiolucencies]. PMID- 2908430 TI - N-methyl-D-aspartate receptors in the spinal cord mediate pressor responses to stimulation of the rostral ventrolateral medulla in the rat. AB - 1. Activation of bulbospinal neurons projecting from the C1 area of the rostral ventrolateral medulla evokes a pressor response. The nature of the neurotransmitters involved in mediating this response at spinal cord level has not been established. 2. Amino acid antagonists were introduced into the spinal subarachnoid space to investigate the role of spinal amino acid receptors in mediating this pressor response in the anaesthetized rat. 3. Intrathecal administration of the amino acid receptor antagonists 2-amino-phosphono valeric acid (2APV), gamma-glutamyl glycine, kynurenate or glutamic acid diethylester (GDEE) attenuated the pressor responses to stimulation of the C1 area. These compounds have been shown to antagonize N-methyl-D-aspartate (NMDA) sensitive receptors. 4. Intrathecal administration of 2APV significantly attenuated the increase in blood pressure produced by injection of NMDA into the spinal subarachnoid space. 5. These results suggest that the pressor response produced by stimulation in the area of the C1 neurons in the rostral ventrolateral medulla of the rat is mediated at least in part by NMDA receptors in the spinal cord. PMID- 2908431 TI - Risk-benefit of specific antihypertensive regimens: relevance of metabolic and haemodynamic effects of alpha 1-blockers. AB - 1. Existing strategies for the control of high blood pressure have had a disappointing impact on coronary heart disease--the major cause of death in hypertension. 2. There is a need for more work to identify the relationship between blood pressure, atheroma and other risk factors. 3. A more aggressive approach to treatment may be indicated, especially in high risk groups. 4. In addition to treatment of blood pressure, other major risk factors (lipids and smoking) must be tackled. 5. Alternative treatment regimens with different mechanisms of action and/or effects on lipids should be evaluated in practice. 6. Selective alpha 1-blockers have potential haemodynamic advantages, improve the lipid profile and are well tolerated as first or second line therapy. PMID- 2908432 TI - Risk-benefits of antihypertensive drugs--beta-blockers. AB - 1. Beta-Blockers are of similar efficacy in the treatment of hypertension to other antihypertensive drugs of first choice; they have a wide spectrum of activity both alone and in combination. 2. Although beta-blockers first appear to worsen the haemodynamic changes of hypertension, subsequently peripheral resistance falls. The cardiovascular reflexes responsible for the responses of posture or other responses requiring normal functioning of alpha-mediated tone are not inhibited. 3. Important contra-indications are asthma and heart failure in susceptible subjects. Lipid soluble drugs have somewhat greater CNS side effects. 4. Triglyceride levels, notably an increase in VLDL and a fall in HDL occur from non-selective agents (less so from beta 1-selective agents) and there is a marginal effect from drugs with relatively high ISA. 5. In contrast to other antihypertensive drugs beta-blockers reduce the myocardial infarction rate in high risk patients (i.e. post-myocardial infarct). Results in primary prevention of mild hypertension have been less promising. 6. Those drugs which are lipid soluble and liver metabolized result in greater variation of plasma concentration after oral administration and some pharmacokinetic drug interactions. Once daily administration is possible with many beta-blockers. 7. beta-Blocking drugs have an established and proven place in the treatment of hypertension. PMID- 2908433 TI - The effect of epanolol on intra-arterial ambulatory blood pressure and baroreceptor heart rate reflex in essential hypertension. AB - 1. The effect of chronic treatment with epanolol, a new cardioselective beta adrenoreceptor antagonist with moderate beta 1-selective intrinsic sympathomimetic activity (ISA), on 24 h ambulatory intra-arterial blood pressure (24 h IABP) and the sino-aortic baroreceptor heart rate (SAB/HR) reflex was investigated in six hypertensive subjects. 2. All subjects demonstrated a greater than 10% reduction in mean arterial pressure with atenolol therapy (100 mg once daily) before entering a randomized, double-blind, placebo-controlled, crossover protocol with epanolol (100 mg twice daily for 4 weeks). 3. Epanolol treatment at this dose was not associated with significant reduction in systolic or diastolic 24 h IABP or heart rate. There was no change in SAB/HR reflex set point, sensitivity or latency with epanolol. 4. beta 1-selective ISA may be undesirable in beta-adrenoceptor antagonists used to treat hypertension. PMID- 2908434 TI - An analysis of the haemodynamic effects of tolbutamide in conscious dogs. AB - 1. In conscious chronically instrumented dogs, tolbutamide (5-45 mg/kg) induced significant dose-related increases in mean arterial pressure and left ventricular end-diastolic pressure. 2. Cardiac output was decreased while heart rate, d(LVP)/dt, and regional myocardial performance at the left ventricle were not significantly affected. Computed total peripheral resistance was increased. 3. Pretreatment with the alpha-antagonist phentolamine (1-1.5 mg/kg) abolished the pressor response. Furthermore, the pressor response to norepinephrine (0.1 microgram/kg) was enhanced by pretreatment with tolbutamide (45 mg/kg). 4. In an isolated tissue preparation using ring segments of canine femoral arteries, neither tolbutamide nor its major hepatic metabolites (carboxytolbutamide, p toluene-sulfonamide and p-toluene-sulfonylurea) caused any smooth muscle contraction. However, pretreatment of these tissues with 10(-4), 10(-3), or 10( 2) mol/l tolbutamide potentiated the contractile response to norepinephrine by up to 19% and to phenylephrine by up to 8%. 5. It was concluded that the pressor effect of tolbutamide arises by potentiating the alpha-adrenoceptor mediated vasoconstrictor action of circulating endogenous catecholamines. PMID- 2908435 TI - Modulation of adrenal catecholamine release by DA2 dopamine receptors in the anaesthetized dog. AB - 1. The effects of DA2 agonist, quinpirole (50 micrograms/kg, i.v.) and a DA2 antagonist, domperidone (50 micrograms/kg, i.v.) on the release of adrenal catecholamines were evaluated in the anaesthetized and vagotomized dog. 2. Stimulations (5 V pulses of 2 ms duration for 3 min) of the splanchnic nerve at frequencies of 1, 3 and 5 Hz were applied randomly before and after injection of the drug. 3. The results show that quinpirole reduces significantly the release of adrenaline at 1 and 3 Hz but not at 5 Hz, while the release of noradrenaline is reduced at 1 Hz but not at 3 and 5 Hz. Inversely, domperidone potentiates significantly the release of both catecholamines at 3 and 5 Hz, but not at 1 Hz. 4. There was no change in basal release of adrenal catecholamines, adrenal blood flow or heart rate after both drug treatments. 5. The mean arterial pressure was not affected by domperidone treatment but there was a significant reduction in basal mean arterial pressure after the injection of quinpirole. 6. There was no change in any of these parameters during electrical stimulation. 7. Therefore, these results strongly suggest that DA2 dopamine receptors are present at the level of the adrenal medulla and that their activation could mediate an inhibitory modulation on the adrenal catecholamines release within a certain range of electrical stimulation. PMID- 2908436 TI - Alpha 1-and alpha 2-adrenoceptors of the circular myometrium from the dioestrous guinea-pig. AB - 1. In order to investigate the nature of the alpha-adrenoceptors mediating contraction of circular myometrium from dioestrous guinea-pigs, the effects of several adrenoceptor antagonists upon log concentration curves to noradrenaline and phenylephrine have been examined. 2. In the presence of ICI 118,551 and nisoxetine both phenylephrine and noradrenaline produced concentration-dependent contractures of circular myometrium from virgin dioestrous guinea-pigs. Noradrenaline was the more potent and produced larger maximal contractions. Indomethacin (1 mumol/l) decreased the maximum effects of phenylephrine but not those of noradrenaline. Xylazine produced indomethacin-sensitive contractions which were not dose-related and which never exceeded 40% of those evoked by noradrenaline. Responses to xylazine and to noradrenaline, but not those to phenylephrine, were reduced in a low calcium solution. 3. Prazosin produced competitive antagonism of the effects of phenylephrine upon preparations of circular myometrium from virgin and parous dioestrous animals; pA2 values were both 8.1. Phentolamine also competitively antagonized the effects of phenylephrine (virgin animals, pA2=7.7). 4. Both prazosin and phentolamine antagonized the effects of noradrenaline upon preparations from virgin dioestrous animals, however, Schild plot analysis did not indicate a simple bimolecular interaction between agonist and receptors. In the presence of prazosin the alpha 2-adrenoceptor antagonist idazoxan produced dose-dependent parallel shifts in the positions of the log concentration-response curves to noradrenaline; the pA2 was 7.7. In the presence of idazoxan or of indomethacin prazosin competitively antagonized the effects of noradrenaline; the pA2 values were 8.5 and 8.2 respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2908437 TI - The effect of two sulphur-containing pesticides, fenitrothion and endosulfan, on glutathione (GSH) content and on GSH S-transferase and gamma-glutamyl transpeptidase activities in midgut gland of the American red crayfish Procambarus clarkii. AB - The glutathione (GSH) system of Procambarus clarkii (P.c.), the American red crayfish, is used as a marker of the effects of Fenitrothion (FT) and Endosulfan (ES), organophosphorus and organochlorinated insecticides, respectively. This system has been shown to be sensitive to different heavy metals poisoning, thus it has a double interest as marker for environmental contamination and as a potential source of xenobiotics or their metabolites to humans, since it is being fished commercially. The GSH content of the organ decreased 24 h after treatment with FT. FT promotes a 2-fold induction of GSH S-transferase (GST) activity at 6 h which is followed by a decrease of it at 24 h. The latter coincides with the decrease in GSH content. GST activity increases again over the control values at 48 h. Only the initial increase in GST activity is coupled with an increase in gamma-glutamyl transpeptidase (transpeptidase activity) (gamma-GT) activity. ES promoted a discrete increase in GSH concentration at the same time as a 2-fold increase in GST activity, again coupled with an increase in gamma-GT activity. The GST induction observed at 6 h with FT and 24 h with ES showed concentration dependency up to 1/4 of the reported LC50 of both pesticides. Higher concentrations showed no further effects on GST activity. The coupled control of the expression of GST and gamma-GT in the hepatopancreas of P.c. is discussed. PMID- 2908438 TI - Voluntary health agencies: experiential classes with class. PMID- 2908439 TI - Interim report of working group on strategies for pooling data in occupational epidemiological studies. PMID- 2908440 TI - Rainbow trout has two genes for growth hormone. AB - We report the primary structures of two mRNA species (GH1 and GH2), each predicted from the cloned cDNA and genomic gene sequences, that encode growth hormone in rainbow trout (Salmo gairdneri). Both GH1 and GH2 mRNA contain open reading frames comprising 630 nucleotides and encode 210 amino acid residues, of which 11 are variant. The translated regions of mRNA are flanked by a short 5' untranslated sequence, which is highly conserved, and a relatively long 3' untranslated sequence, which is highly divergent. The differences at the 3' untranslated regions suggest that the GH1 and GH2 mRNA originate from different loci. RNA blot analysis of trout pituitary RNA using an oligonucleotide probe specific for the GH2 sequence indicates that the cloned gene is expressed. The GH1 and GH2 mRNA likely are transcribed from two distinct loci, which were duplicated during tetraploidization of the salmonid genome between 50 and 100 million years ago. PMID- 2908441 TI - Changes in polyadenylation of lactate dehydrogenase-X mRNA during spermatogenesis in mice. AB - The expression of the mRNA for mouse testicular lactate dehydrogenase (LDH-X) was examined by RNA:cDNA hybridization in situ in the testis and by Northern analyses of meiotic and postmeiotic spermatogenic cell populations. Silver grains accumulated in cells inside the second layer from the periphery of the seminiferous tubule, confirming previous findings that LDH-X mRNA first appears in the spermatocyte and continues to accumulate until the late spermatid stage. Northern analyses showed that meiotic and postmeiotic cells contained 1.2 and 1.3 kb classes of hybridizing mRNA, respectively. RNase H digestion of oligo (dT) hybridized RNA and poly(U)-Sepharose column chromatography with differential elution by formamide revealed that the difference in size of the two classes of mRNAs was due to the poly(A) tail length of the LDH-X mRNA. When the distribution of the LDH-X mRNA was examined across polysome gradients, both mRNAs were partially associated with polysomes. These results suggest that the changes in the polyadenylation of LDH-X mRNA were associated with the meiotic division during spermatogenesis in the mouse. They raise the possibility that the stable accumulation of the LDH-X mRNAs in the postmeiotic cells is enhanced by poly(A) tails of increased length. PMID- 2908442 TI - Cortical cytoskeleton of giant moth eggs. AB - Unfertilized eggs of several species of giant moths contain a substantial cortical cytoskeleton. This structure is assembled during oogenesis, and contains actin as a major fibrillar component. The presence of actin was confirmed by gel electrophoresis and binding to phalloidin, DNase I, and a monoclonal antibody against cytoskeletal actin. Several lines of evidence suggest that the fat body is a source of the actin in the oocyte and that the transport and acquisition of actin by the ovary are similar to the mechanism of vitellogenin acquisition. A possible role for the cortical cytoskeleton in directing early embryogenesis is discussed. PMID- 2908443 TI - A persistent postsynaptic modification mediates long-term potentiation in the hippocampus. AB - Long-term potentiation (LTP) is a long-lasting enhancement of synaptic transmission that can be induced by brief repetitive stimulation of excitatory pathways in the hippocampus. One of the most controversial points is whether the process underlying the enhanced synaptic transmission occurs pre- or postsynaptically. To examine this question, we have taken advantage of the novel physiological properties of excitatory synaptic transmission in the CA1 region of the hippocampus. Synaptically released glutamate activates both NMDA and non-NMDA receptors on pyramidal cells, resulting in an excitatory postsynaptic potential (EPSP) with two distinct components. A selective increase in the non-NMDA component of the EPSP was observed with LTP. This result suggests that the enhancement of synaptic transmission during LTP is caused by an increased sensitivity of the postsynaptic neuron to synaptically released glutamate. PMID- 2908444 TI - Low- and high-voltage-activated calcium currents: their relationship to the site of neurotransmitter release in an identified neuron of Helisoma. AB - In this study we have characterized two types of Ca2+ currents in identified neuron B5 of Helisoma and have examined the relationship between these currents and neurotransmitter release. Neuron B5 contains low-voltage-activated (LVA) and high-voltage-activated (HVA) Ca2+ currents. These currents have distinct electrophysiological and pharmacological properties. To gain access to the site of neurotransmitter release, we used a model system in which somata that do not extend neurites assume the role of neurotransmitter release. Before somata gain the ability to release neurotransmitter, they contain LVA and HVA Ca2+ currents. After 3 days of culture, when spherical somata have gained the secretory capacity, only the HVA Ca2+ current is present. Experiments were also performed when neurite extension was permitted. These data indicate that neurons with processes have a differential distribution of Ca2+ currents. The soma, which does not release neurotransmitter, contains both LVA and HVA Ca2+ currents, while distal secretory processes contain only HVA current. PMID- 2908445 TI - The cell biology of the nerve terminal. PMID- 2908446 TI - Glutamate neurotoxicity and diseases of the nervous system. PMID- 2908447 TI - Expression of the Alzheimer amyloid precursor gene transcripts in the human brain. AB - An alternate form of the Alzheimer amyloid protein precursor mRNA that encodes a protease inhibitor domain has recently been reported. Oligonucleotide probes that differentiate between the two mRNAs are used to describe the expression of each amyloid precursor transcript in the human brain. RNA blot analyses show that one of the mRNAs is expressed selectively in the nervous system, that the two messages display different regional distributions in the adult human brain, and that the expression of the two mRNAs is differentially affected in Down's syndrome brain and in Alzheimer's disease frontal cortex. In situ hybridization shows that the two transcripts display the same laminar distribution in the adult cortex but that the transcripts differ significantly in their levels of expression in pyramidal cells of the hippocampus. PMID- 2908448 TI - Spatial regulation of homeobox gene fusions in the embryonic central nervous system of transgenic mice. AB - The spatially restricted expression of mammalian homeobox genes in teh embryonic central nervous system (CNS) provides an opportunity to study the basis of spatial gene regulation in mammalian development. Here, we define a regulatory region of the murine Hox 1.3 gene that mediates such a region-specific expression pattern. The Hox 1.3 gene contains two exons, encodes a putative protein of 270 amino acids, and is expressed preferentially in the spinal cord at midgestation. We have analyzed transgenic mice containing various Hox 1.3 DNA fragments fused to reporter sequences, such as a human growth hormone gene fragment or the E. coli lacZ structural gene. As shown by RNAase protection assays or by in situ analyses of beta-galactosidase activity, several hybrid genes are expressed in the embryonic central nervous system in a spatially restricted manner, along both the rostrocaudal and dorsoventral axes. A 912 nucleotide sequence located immediately upstream of the Hox 1.3 coding sequence is sufficient to direct expression to the dorsolateral cells of the brachial spinal cord. PMID- 2908449 TI - Immunological, morphological, and electrophysiological variation among retinal ganglion cells purified by panning. AB - Two different monoclonal antibodies to the Thy-1 antigen, T11D7 and 2G12, were used to purify and characterize retinal ganglion cells from postnatal rat retina. Although Thy-1 has been reported to be a specific marker for ganglion cells in retina, retinal cell suspensions contained several other types of Thy-1-positive cells as well. Nevertheless, a simple two-step "panning" procedure allowed isolation of ganglion cells to nearly 100% purity. We found that postnatal ganglion cells differed in antigenic, morphological, and intrinsic electrophysiological characteristics, and that these properties were correlated with one another. Minor variations of this panning protocol should allow rapid, high yield purification to homogeneity of many other neuronal and glial cell types. PMID- 2908450 TI - Interactions between entorhinal axons and target hippocampal neurons: a role for glutamate in the development of hippocampal circuitry. AB - A coculture system consisting of input axons from entorhinal cortex explants and target hippocampal pyramidal neurons was used to demonstrate that glutamate, released spontaneously from afferent axons, can influence both dendritic geometry of target neurons and formation of presumptive synaptic sites. Dendritic outgrowth was reduced in hippocampal neurons growing on entorhinal axons when compared with neurons growing off the axons. Presumptive presynaptic sites were observed in association with hippocampal neuron dendrites and somas. HPLC analysis showed that glutamate was released from the explants in an activity- and Ca2(+)-dependent manner. The general glutamate receptor antagonist D glutamylglycine significantly increased dendritic outgrowth in pyramidal neurons associated with entorhinal axons and reduced presumptive presynaptic sites. Tetrodotoxin and reduction of extracellular Ca2+ also promoted dendritic outgrowth and reduced the formation of presumptive synaptic sites. The results suggest that the neurotransmitter glutamate may play important roles in the development of hippocampal circuitry. PMID- 2908451 TI - [Autoimmune sensorineural hypoacusis]. PMID- 2908452 TI - [Soldering procedure in dentistry. Tips for beginners and experienced workers]. PMID- 2908453 TI - [Soldering technics for crowns and bridges]. PMID- 2908454 TI - A comparison of the long-term and short-term regulations of tyrosine hydroxylase activity. AB - The activity of tyrosine hydroxylase, the enzyme that catalyzes the rate-limiting step in catecholamine biosynthesis, increases in postganglionic sympathetic neurons following electrical stimulation of their afferent preganglionic input. Two types of changes in enzyme activity occur: an acute increase and a delayed and long-lasting increase. The pharmacological mechanisms involved in these transsynaptic effects and the biochemical mechanisms underlying the changes in tyrosine hydroxylase activity are discussed. PMID- 2908455 TI - Preparation of a highly coupled H(+)-transporting ATP synthase from pig heart mitochondria. PMID- 2908456 TI - Resolution and reconstitution of F0F1-ATPase in beef heart submitochondrial particles. PMID- 2908457 TI - Electron microscopy of single molecules and crystals of F1-ATPases. PMID- 2908458 TI - Use of monoclonal antibodies to purify oligomycin sensitivity-conferring protein and to study its interactions with F0 and F1. PMID- 2908459 TI - Purification and properties of the ATPase inhibitor from bovine heart mitochondria. PMID- 2908460 TI - Purification of the proton-translocating ATPase from rat liver mitochondria using the detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propane sulfonate. PMID- 2908461 TI - Rapid purification of F1-ATPase from rat liver mitochondria using a modified chloroform extraction procedure coupled to high-performance liquid chromatography. PMID- 2908462 TI - Purification of alpha and beta subunits and subunit pairs from rat liver mitochondrial F1-ATPase. PMID- 2908463 TI - Isolation and characterization of an inactivated complex of F1F0-ATPase and its inhibitory factors from yeast. PMID- 2908464 TI - Purification of F1F0 H(+)-ATPase from Escherichia coli. PMID- 2908465 TI - Use of lambda-unc transducing phages in genetic analysis of H(+)-ATPase mutants of Escherichia coli. PMID- 2908466 TI - Proton-conducting portion (F0) from Escherichia coli ATP synthase: preparation, dissociation into subunits, and reconstitution of an active complex. PMID- 2908467 TI - Preparation and reconstitution of F1F0 and F0 from Escherichia coli. PMID- 2908468 TI - Use of isolated subunits of F1 from Escherichia coli for genetic and biochemical studies. PMID- 2908469 TI - Analysis of Escherichia coli mutants of the H(+)-transporting ATPase: determination of altered site of the structural genes. PMID- 2908470 TI - Proton permeability of membrane sector (F0) of H(+)-transporting ATP synthase (F0F1) from a thermophilic bacterium. PMID- 2908471 TI - Rate constants and equilibrium constants for the elementary steps of ATP hydrolysis by beef heart mitochondrial ATPase. PMID- 2908472 TI - ATP formation in mitochondria, submitochondrial particles, and F0F1 liposomes driven by electric pulses. PMID- 2908473 TI - Synthesis of enzyme-bound adenosine triphosphate by chloroplast coupling factor CF1. PMID- 2908474 TI - Divalent azido-ATP analog for photoaffinity cross-linking of F1 subunits. PMID- 2908475 TI - Synthesis and use of an azido-labeled form of the ATPase inhibitor peptide of rat liver mitochondria. PMID- 2908476 TI - Benzophenone-ATP: a photoaffinity label for the active site of ATPases. PMID- 2908477 TI - Use of ADP analogs for functional and structural analysis of F1-ATPase. PMID- 2908478 TI - Modifiers of F1-ATPases and associated peptides. PMID- 2908479 TI - A nonlinear approach for the analysis of different models of protein-ligand interaction: nucleotide binding to F1-ATPase. PMID- 2908480 TI - Identification of essential residues in the F1-ATPases by chemical modification. PMID- 2908481 TI - Determination of the stoichiometry and arrangement of alpha and beta subunits in F1-ATPase using monoclonal antibodies in immunoelectron microscopy. PMID- 2908482 TI - Metachromatic leukodystrophy: report of four cases. PMID- 2908483 TI - A controlled trial of esmolol for the induction of deliberate hypotension. AB - Twenty-five patients scheduled for lumbar fusion or cerebrovascular surgery were enrolled in an open label treatment controlled study comparing blood pressure and heart rate responses during deliberate hypotension with either esmolol or nitroprusside during steady-state N2O/isoflurane anesthesia. The first 5 patients were empirically assigned to the esmolol group; the remaining 20 patients were randomized to receive either esmolol or nitroprusside. The target of 15% reduction in mean arterial pressure (MAP) from baseline determined during anesthesia was attained with esmolol 195 +/- 10 micrograms/kg/min (mean +/- SEM) for the group (n = 15) or nitroprusside 1.9 +/- 0.3 micrograms/kg/min for the nitroprusside group (n = 10). Nitroprusside use was associated with a 15.9 +/- 5.3% increase in heart rate compared to a 12.1 +/- 2.2% decrease in the esmolol group (p = 0.0001 between groups). Upon termination of the hypotensive infusions, nitroprusside patients had a MAP increase of 13.9 +/- 5.5% above baseline (p less than 0.05 compared to prehypotension) while the 7.4 +/- 3.5% increase in the esmolol group was not statistically significant. Although 30% of nitroprusside patients overshot their baseline MAP by more than 25%, no esmolol patients had this degree of rebound. One esmolol patient had a brief period of atrial premature contractions. No patient in either group suffered any adverse reaction to hypotension. It is concluded that in moderate doses esmolol is a safe and effective hypotensive agent during isoflurane anesthesia, with no reflex tachycardia and no significant potential for rebound hypertension. A MAP reduction of 30% from preanesthesia baseline was readily obtained with this combination. PMID- 2908484 TI - Dopamine and new dopamine analogs: receptors and clinical applications. AB - Division of dopamine (DA) receptors and alpha- and beta-adrenoceptors into two subtypes provides a pharmacological basis for the clinical use of DA and new DA receptor agonists in anesthesia and critical care medicine. First, differential receptor activation explains why three distinct cardiovascular and renal responses can be obtained at low, medium, and high infusion rates of DA. Low infusion rates, in which DA1 and DA2 receptors are activated, are being increasingly used to improve renal perfusion and to treat oliguric states. The medium dose range (activation of beta1-adrenoceptors) is used for treatment of heart failure. The high dose range (activation of alpha-adrenoceptors) is used for treatment of shock. Second, selective DA1 and relatively selective DA2 agonists and agonists with different combinations of DA and receptor activity other than DA have been synthesized and are being investigated for the treatment of congestive heart failure and hypertension. Some of these compounds could have advantages over DA for acute therapy. Future availability of these drugs in anesthesia and critical care settings will depend to a great extent on input from anesthesiologists concerning potential new uses and willingness to conduct clinical investigations. PMID- 2908485 TI - Clonidine and other alpha2 adrenergic agonists: strategies for the rational use of these novel anesthetic agents. AB - Clonidine and other clinically available alpha-2 adrenergic agonists reduce inhalational and narcotic anesthetic requirements while providing hemodynamic stability during stressful periods of surgery. Like the opiates, the alpha-2 adrenergic agonists are potent analgesics when given systemically, epidurally, or intrathecally. Their effects are reversed by alpha2 adrenergic antagonists. Newer and more selective alpha2 adrenergic agonists are more potent in their anesthetic action than the clinically available opiates. The important difference is that these agents do not appear to be respiratory depressants and do not have an addiction liability of the opioid type. They have anxiolytic properties and therefore can be potentially useful in the preanesthetic period. This drug class has the potential to provide many of the component effects required for perioperative care. For these reasons, the alpha2 adrenergic class of drugs should be important in the future of anesthesia. PMID- 2908486 TI - Inhibition of the cutaneous response to histamine by H1-blocking agents. Quantitative evaluation of microvascular changes in the skin after histamine challenge and a comparison of the effects of a single intake of cetirizine and terfenadine. AB - A controlled, randomized, double-blind, cross-over study was performed in 10 healthy volunteers in order to compare changes of cutaneous blood flow values (CBFV, laser Doppler flowmetry, Periflux, Perimed, S) in histamine-challenged skin before and after administration of a capsule containing either 10 mg cetirizine or 60 mg terfenadine. The overall pattern of the basal cutaneous wheal and flare response to the agonists (histamine: aqueous solution: Hsol, or Phazet: Hprick) and control saline solution, showed the expected range of clinical effects, i.e. Hsol greater than Hprick greater than saline. Similarly, the increase of CBFV on the flare area was higher around the histamine injections as compared with saline. Surprisingly, CBFV was decreased at the site of Hsol and Hprick injections as compared with the levels recorded at the control injections. The following changes were noted after intake of H1-blocking agents. (1) There was a reduction of the areas of wheal and flare at all injection sites after administration of the H1 blockers, this reduction being consistently greater under cetirizine than terfenadine. (2) CBFV, measured 1 cm from the site of Hsol injection (i.e., within the area of normal flare response), was decreased only with cetirizine. In the smaller flare area induced by Hprick, CBFV was equally suppressed by both drugs. (3) At the site of agonist injection, along with a reduction of the size of the wheal, we observed significant increases in CBFV after drug intake. Under these experimental conditions, this quantitative pharmacologic in vivo assay of agonist-antagonist interactions suggests that after initial administration of normally prescribed doses, cetirizine may possess more anti-H1 activity than terfenadine. PMID- 2908487 TI - Echocardiography at the American Heart Association Scientific Sessions: an editorial perspective. PMID- 2908488 TI - Viewpoint on the echocardiographic presentations at the American College of Cardiology Annual Scientific Sessions. AB - Overall, echocardiography was well represented at the American College of Cardiology Annual Scientific Sessions and accounted for input into almost 25% of all abstracts presented. This included not only specialized sessions, predominantly attended by echocardiographers, but the clinical and surgical sessions dealing with virtually any and all forms of heart disease. This is a versatility of which we can be justifiably proud. The newer technique of catheter mounted ultrasound transducers for intravascular imaging is exciting, and we all await further developments in this field. Finally, it would appear the ground is still fertile for investigation into left ventricular function as it relates to acute myocardial infarction in an era of evermore frequent intervention. PMID- 2908489 TI - Failure of expression of alpha-3-L-fucosyltransferase in human serum is coincident with the absence of the X (or Le(x)) antigen in the kidney but not on leucocytes. AB - The X antigen, beta Gal(1----4)[alpha Fuc(1----3)]beta GlcNAc-R, is mostly found in epithelial cells of the digestive tract, proximal convoluted tubules of the kidney, and granulocytes. The alpha-3-L-fucosyltransferase responsible for synthesis of this antigen is normally present in the serum, but we found 2 individuals, a mother and her daughter, who lack more than 90% of the serum fucosyltransferase. They are of African origin and are both Le(a-b-). The young girl suffers from a congenital kidney anomaly: oligomeganephronic hypoplasia. Her kidney tubules are devoid of X antigen. However, her mother and herself normally possess the X antigen on granulocytes and its sialylated form on monocytes. Anephric patients showed reduced serum alpha-3-L-fucosyltransferase activity, suggesting that the kidney contributes to an important fraction of serum enzymic activity. It, therefore, appears that there are distinct genetic controls governing expression of the X antigen in different body compartments. Possibly, different alpha-3-L-fucosyltransferases could be at work in kidney and leucocytes. PMID- 2908490 TI - Correlation of class I DNA TaqI and PvuII restriction HLA gene fragments with serologic HLA-C alleles. PMID- 2908491 TI - Polymorphism of immunoglobulin lambda constant region genes in populations from France, Lebanon and Tunisia. AB - Polymorphism of immunoglobulin lambda constant region (IGLC) genes has been studied in French, Lebanese and Tunisian people. The human IGLC polymorphisms appear as EcoRI restriction fragment length variations-8, 13, 18 or 23 kb-, these polymorphic fragments being related to a number of IGLC genes varying from six to nine per haploid genome. DNAs digested with the endonucleases EcoRI and HindIII were hybridized to a human IGLC probe and an immunoglobulin lambda intervening sequence region probe containing the J lambda 2 gene segment. Restriction fragments detected in Southern hybridizations were assigned to the IGLC locus map. Family studies allowed us to confirm the allelic nature of four of the different EcoRI restriction fragments observed. Frequencies of the corresponding alleles in French, Lebanese and Tunisian populations were determined and compared. The decrease of the 8-kb fragment (allele A1) frequency and, conversely, the increase of that of the 13-kb and 18-kb fragments (alleles A2 and A3) seemed to be correlated to a Negroid African contribution in the gene pool more important in Tunisia than in Lebanon. PMID- 2908492 TI - Southern blot analysis of major histocompatibility genes of lpr mice. AB - Several recent functional and immunofluorescent studies have suggested that abnormal major histocompatibility genes may be expressed in mice homozygous for the autoimmune disease-accelerating lpr (lymphoproliferation) gene. In an effort to establish the molecular basis of the expression of abnormal MHC molecules in these mice, we used MHC class I- and class II-specific cDNAs to probe endonuclease-digested genomic DNA from strains expressing lpr to look for restriction fragment length polymorphisms (RFLPs). The RFLP pattern of MRL/Mp lpr/lpr (MRL/lpr) DNA, as determined using five restriction enzymes, was identical to that of MRL/MP-+/+ and typical of the H-2k haplotype exhibited by C3H/HeSnJ and AKR/J, which are the two H-2k haplotype strains from which MRL was derived. DNA from C57BL/6-lpr/lpr (B6/lpr) exhibited a pattern similar to C57BL/6, again indicating that the lpr gene did not alter MHC genes, within the limitations of this approach. Because macrophages derived from lpr mice had been specifically reported to express altered MHC haplotypes, DNA was prepared from MRL/lpr peritoneal macrophages and Southern blotting was performed using probes for I-A beta and I-E beta. The patterns observed were typical of H-2k DNA. The data thus indicate that the abnormalities of MHC genes previously observed in lpr mice may be due to the influence of other genes on MHC gene products, but are probably not due to alterations in MHC genes themselves. PMID- 2908493 TI - Recent results in the physiology and pathophysiology of growth hormone secretion. PMID- 2908495 TI - Dental evidence of survived calamities in wild animals. PMID- 2908494 TI - [Neurosecretory dysfunction of growth hormone]. PMID- 2908496 TI - Subcutaneous tissue flaps in the limbs: an anatomical and clinical approach. AB - We present an anatomical study and clinical applications of a subcutaneous tissue flap in the limbs. This tissue, located between dermis and muscular aponeurosis, is an anatomical entity nourished by a well-developed vascular network. It is used mainly as a local flap able to bear a skin graft. Elastic, resistant, and well padded, it gives good coverage for soft tissue defects while leaving the surrounding skin untouched. In some circumstances, this simple technique can avoid delicate procedures, such as free flaps, or unsightly donor site defects after fasciocutaneous flaps. PMID- 2908497 TI - Extremity reconstruction using the "fillet of sole" flap. AB - Foot skin can be used in traumatic nonreplantable leg amputations as an immediate neurovascular free flap for proximal stump reconstruction. The thick, glabrous skin on the sole of the foot provides durable, sensate coverage. The flap is large, avoids a secondary donor site, and can survive on either the dorsalis pedis or posterior tibial artery if one preserves the connecting deep plantar branch of the dorsalis pedis artery. Two cases of immediate stump reconstruction using the "fillet of sole" flap are presented. PMID- 2908498 TI - [Solder melting torches]. AB - In this study about melting and torchs employed in solder in fixed prosthodontics, it's analysed the accurate melting, adequate quantity, as well as protection of adjacent tissues with an accurate anti-melting. The torch chosen is the oxyacetylene burner, because its greater calorific power. PMID- 2908499 TI - A simple, rapid method for the purification of poly A+ RNA. PMID- 2908500 TI - An inexpensive method of drying multiple agarose gels. PMID- 2908501 TI - High molecular weight DNA isolation by guanidine hydrochloride or guanidinium isothiocyanate treatment. PMID- 2908502 TI - Correlation of class I DNA Pvu II restriction HLA gene fragments with serologic alleles. AB - Restriction enzyme site polymorphisms for Pvu II endonuclease are examined in a panel of DNAs isolated from peripheral blood lymphocytes of HLA-typed individuals. 21 polymorphic bands are detected from a total of 39 restriction fragments analyzed, only 9 of them corresponding to common variable morphs. Three polymorph fragments only correlate with known HLA-A and -B serologic alleles. PMID- 2908503 TI - Variation in restriction fragment length and methylation pattern of rat MHC class I genes. AB - Rat MHC (RT.1) class I genes were analyzed by performing Southern blot analysis of digests of genomic DNA isolated from three inbred rat strains using a human derived HLA cDNA probe specific for class I genes. A large number of hybridizing restriction fragments indicated that the rat MHC is a large multigene family. Polymorphic class I DNA restriction fragments specific for the different haplotypes were found for three restriction enzymes used, indicating a high degree of restriction fragment length polymorphism of RT.1 class I genes. Analysis of the methylation state of class I RT.1 genes showed that they are hypermethylated to an extent that is haplotype specific. Furthermore, variation in number and size of Hpa II fragments were observed when comparing liver and spleen DNA from two rat strains sharing the same haplotype. This indicates methylation variation between these organs for RT.1 class I genes. PMID- 2908504 TI - Glycolipid-directed FH6 monoclonal antibody recognizes high molecular weight glycoprotein antigen carrying sialyl Lex-i determinant in the culture supernatant of PC-9 cells. AB - The properties of the antigen recognized by monoclonal antibody FH6 have been analyzed. FH6 was originally generated against a glycolipid, i.e. a difucoganglioside isolated from human colonic adenocarcinoma, and specifically reacts with sialyl Lex-i determinant. Several culture supernatants of human carcinoma cell line cells were found to have high levels of FH6-reactive antigen, and PC-9, a human lung carcinoma cell line was used for the analysis. A solid phase sandwich radioimmunoassay was performed to detect the antigen. The antigenic activity was extractable in 0.6 M PCA or 7% TCA, and was sensitive to mild alkaline treatment and to Pronase digestion. Most of the antigen was eluted in the void volume of a Sepharose CL-2B column, which indicates that its molecular weight is greater than several million. It was eluted from a DEAE cellulose column at a NaCl concentration in the range of 0.2-0.25 M. The immunoaffinity-purified antigen has a high carbohydrate content of more than 80%. These data indicate that the antigen recognized by FH6 in the culture supernatant of PC-9 is not a glycolipid, but a high molecular weight glycoprotein which could be referred to as a mucin, or a proteoglycan, which contains keratan-sulfate like glycosaminoglycan chains, as judged from the results of the glycosidase treatments. PMID- 2908505 TI - [Limb vasodilation provoked by stimulation of the carotid sinus. Importance of histaminergy in the dog]. AB - The vasodilator reflex induced by baroreceptor stimulation was studied on the hindlimbs of the dog. The reflex was induced by norepinephrine (1 microgram/kg) either by intravenous injection or by direct injection into the carotid sinus. In other experiences, the baroreceptor stimulation was obtained by distension of the sinus by rapid injection of 100 ml of physiological serum. The vascular response was studied by recording the hindlimbs blood flow. One of the limbs was previously pretreated by mepyramine and cimetidine (blockage of histaminergic H1 and H2 receptors). During the first minute after the baroreceptor stimulation, blood samples were collected from the venous blood of hindlimbs for histamine assay (fluorometric assay). Our results show: a much lower vasodilation on the limb pretreated by histamine antagonist, a significant increase during the reflex vasodilation of histamine blood levels measured in the efferent blood of hindlimbs. These results, obtained in experimental conditions as physiological as possible (blood perfusion of the limbs with "natural" hemodynamic parameters) permit to conclude that the vasodilation induced by baroreceptor reflex is at least partially histaminergic in the dog. PMID- 2908506 TI - [Treatment of rheumatoid arthritis: drugs which induce remission]. PMID- 2908507 TI - Factors affecting the natural history of human immunodeficiency virus infection. AB - Human immunodeficiency virus (HIV) establishes latent infection in CD4 lymphocytes and macrophages. It can destroy CD4 cells by direct virus cytotoxicity, indirectly through the host response against HIV-infected cells, or by both means. Cells of the macrophage lineage are generally not destroyed but can serve as a reservoir of virus. HIV also causes functional impairment in remaining infected and uninfected cells. After exposure to infection by sexual, blood or maternofetal contact, about half the contacts become infected with HIV. Factors influencing the inoculum derived from the infected person include type of contact, phase of infection and local factors enhancing HIV replication or excretion. In the exposed person, genetic factors and systemic or local events such as infection or inflammatory injury may influence relative susceptibility. After infection with HIV, a number of outcomes may be seen, including symptomless carriage, with or without lymphadenopathy, or symptomatic disease, including the AIDS-related complex, acquired immune deficiency syndrome and HIV encephalopathy. Infection, multiple pregnancy and infancy are associated with increased or more rapid progression to symptomatic disease; malnutrition and immunosuppressive drugs may exert a similar effect. Genetic factors appear to affect disease susceptibility. Mechanisms influencing progression can be divided into those affecting the rate of HIV replication, those that determine the host response to HIV, and those mediated by other immunosuppressive influences. The host's balance with HIV thus resembles that of a tightrope walker, any force tending to tip him towards a catastrophic and irretrievable decline. PMID- 2908508 TI - Prediction of the frequencies of restriction endonuclease recognition sequences using di- and mononucleotide frequencies. AB - The calculation of probabilities of nucleotide sequences from the frequencies of dinucleotides is described. The dinucleotide and mononucleotide frequencies used can be obtained from nearest neighbor analysis or from databank sequences. If dinucleotide and mononucleotide frequencies from nearest neighbor analysis are used, probabilities for oligonucleotides can be calculated for genomes in which there is little or no sequence data. Within a given genome, a broad range of probabilities for hexanucleotide palindromes with the same base composition is predicted and shown (14). PMID- 2908509 TI - Luciferase reporter gene vectors for analysis of promoters and enhancers. PMID- 2908510 TI - Taq I restriction polymorphism of HLA class-I genes, and hybridization with HLA-A and HLA-B specific probes. AB - Restriction enzyme site polymorphisms for Taq I endonuclease are examined in a panel of DNAs of HLA-typed individuals and families. Using a full-length DNA probe, 13 polymorphic bands were detected in a total of 31 restriction fragments analyzed. Only one of them (the 3.5-kb polymorphic band) correlated absolutely with serological allele B27, as already established. The A- and B-specific probes recognized only a very small subset (4 for the A probe, and 2 for the B probe) of the DNA fragments which were hybridized with the full-length DNA probe. For each of these two loci, a frequent polymorphism was described, which correlated with serologic haplotypes in several families studied. PMID- 2908511 TI - Ontogeny of human suppressor inducer T cell subset. AB - A T cell subset (T4+,2H4+) has recently been identified, which acts as an inducer of T8+ suppressor cells; however 2H4 molecules have not been detected in thymuses from normal individuals or on the surface of immature thymocyte clones. In the present study, T4+,2H4+ and T8+,2H4+ cells have been found in maternal and new born blood samples. However, only a small percentage of 2H4+ cells were detected in human fetal thymus, bone marrow, liver and spleen, thus suggesting that T cells acquire these molecules only in circulation and at a late stage of maturation. PMID- 2908512 TI - A 1.4-kb BamHI restriction fragment of genomic DNA correlates with the birdshot retinochoroidopathy susceptibility gene. PMID- 2908513 TI - Taq I polymorphism of HLA class I genes in an ankylosing spondylitis family. AB - A 3.5-kb HLA class I fragment is polymorphic in an ankylosing spondylitis (AS) family. All B27 AS patients show the 3.5-kb band, which is also present in B12 AS patients in this family. When hybridized with an HLA-B-specific probe, the polymorphic band is revealed in B12 patients, but not in B27 patients. PMID- 2908514 TI - Polymorphism of the complement C3 gene in the Lebanese population. AB - The C3 protein polymorphism was studied in 300 unrelated Lebanese. The gene frequencies were calculated and compared with other populations. DNA samples digested with various endonucleases were hybridized with a C3 probe, which was found to detect a frequent Sac I restriction fragment length polymorphism (RFLP) and a less frequent Taq I RFLP in the Lebanese population, as well as in the French populations. PMID- 2908515 TI - [Perspectives in the treatment of arterial hypertension: interventions at the dopaminergic system level]. PMID- 2908516 TI - The natural history of tolerance to the benzodiazepines. AB - Dependence on benzodiazepines following continued use is by now a well-documented clinical phenomenon. Benzodiazepines differ in their dependence potential. The present studies were aimed at examining the possibility that differential rates of tolerance development might account for differences in dependence risk. Four studies are reported. The first three studies concerned normal subjects. The development of tolerance over a fifteen day period was demonstrated for three different benzodiazepines (ketazolam, lorazepam and triazolam) using two paradigms. Tolerance in terms of a reduction in effectiveness of a repeated given dose was most notable for the benzodiazepine with a medium elimination half-life (lorazepam) for physiological, behavioural and subjective measures. In the case of the drug with the longest elimination half-life (ketazolam) reduction in effectiveness could only be assumed to be occurring if account was taken of the steady increase in plasma concentrations of active metabolites. For this drug it seemed that the physiological measures were those most likely to demonstrate the development of tolerance. Although triazolam showed few significant drug effects on this paradigm (testing being 12 hours after ingestion of this short half-life benzodiazepine), tolerance was seen to develop on some subjective measures. Using an alternative method of testing tolerance, assessing responses to a diazepam challenge dose, a high degree of tolerance on two-thirds of the measures was observed in subjects when pretreated with the benzodiazepine with the most marked accumulation of active metabolites (ketazolam). The other two drugs also led to tolerance development on a range of measures; this was more marked for lorazepam than triazolam. Blunting of the growth hormone response to diazepam was the most sensitive and reliable method of detecting tolerance to the benzodiazepines. Symptoms on discontinuation of the two weeks' intake of the benzodiazepines were marked for all the drugs but unrelated to either the tolerance induced or the elimination half-life of the particular drug. A further clinical study revealed that tolerance persisted in a group of long-term benzodiazepine users for between four months and two years following complete abstinence from the drug. These patients appeared to be less affected by diazepam in terms of its commonly observed subjective effects, regardless of their original medication. These ex long-term users of benzodiazepines were, however, more likely to manifest two specific types of effects--immediate 'symptom' reduction and exacerbation of 'withdrawal symptoms' over the subsequent week.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2908517 TI - [The physiopathology of migraine]. PMID- 2908518 TI - [Application of DNA analysis to the study of hereditary neurological diseases]. PMID- 2908520 TI - Agglutinogens and fimbriae of Bordetella pertussis. AB - Agglutinogen 2 (AGG2) of Bordetella pertussis is a fimbrial antigen and therefore a potential adhesin and acellular vaccine component. AGG2 was found to dissociate only under harsh conditions into the subunits of mol. wt. 22500 seen in SDS-PAGE. Results from studies of agglutinogen 3 (AGG3) are presented which confirm previous findings from this Laboratory that AGG3 is also a fimbrial protein but with a subunit mol. wt. of 22000. The amino acid sequence of AGG2, deduced from the nucleotide sequence of the gene encoding it, was used as a basis for synthesis of three peptides. Coupled to Keyhole Limpet Haemocyanin (KLH), the peptides were immunogenic in mice, inducing antibodies which bound well to homologous peptide in ELISA but poorly to intact fimbriae. Monoclonal and polyclonal serotype-specific antibodies failed to react significantly with the peptides or their KLH-conjugates. These results indicate that the synthetic peptides do not represent the serotype 2 epitope. Mice immunized with purified AGG2 or AGG3 were found to be protected against respiratory infection with B. pertussis. Results presented here indicate that this protection is, to a large extent, serotype-specific and that immunization of mice with AGG2 or AGG3 can lead to a change in serotype of the infecting strain. These results are analogous to findings from epidemiological studies of the protection induced in children by whole cell vaccines. They reaffirm the importance of both AGG2 and AGG3 as components of whole cell and acellular vaccines. PMID- 2908519 TI - Japanese clinical trials with Takeda acellular pertussis vaccine. AB - Japanese clinical trials with Takeda acellular pertussis vaccine revealed that infants 3 to 8 months of age reacted sufficiently to the vaccine: anti-PT ant-FHA levels after vaccination were as high as those observed with 2 year old children. No substantial difference in general reactions was noted between infants and 2 year old children. Less local reactions were noted in infants. PMID- 2908521 TI - U.S. clinical trials with Takeda acellular pertussis vaccine. PMID- 2908522 TI - Structural and functional properties of a 69-kilodalton outer membrane protein of Bordetella pertussis. AB - A-69-kDa outer membrane protein present on virulent Bordetella pertussis cells is recognized by the agglutinating monoclonal antibodies BPE3, BPD8, and BPE8. The amino acid composition of this protein, purified from heat extracts of B. pertussis BP353 cells, is different from that of the two major fimbrial antigens of B. pertussis, which is consistent with its being a nonfimbrial protein based on other criteria. Western blot analysis using the monoclonal antibody BPE3 demonstrated that a slightly larger but antigenically cross-reactive protein is also expressed by Bordetella bronchiseptica and Bordetella parapertussis. In addition, a large molecular weight species of about 180-kDa is found in outer membrane extracts of B. bronchiseptica which may represent a precursor form of the protein or indicate that the protein can exist as an oligomer. The monoclonal antibody BPD8 directed against the 69-kDa protein almost completely inhibited the enzymatic activity of adenylate cyclase purified from B. pertussis and also inhibited the intoxication of mammalian cells by this enzyme. Since little enzymatic activity was found associated with the purified 69-kDa protein, these data suggest a role for the 69-kDa protein in regulating the adenylate cyclase toxin of B. pertussis. An additional monoclonal antibody directed against the 69 kDa protein, BPE8, decreases lymphocytosis and delays death in mice receiving a respiratory challenge of virulent B. pertussis cells. These studies suggest that further investigation into the role of this protein as a protective antigen and vaccine candidate is warranted. PMID- 2908523 TI - The vir locus and phase-variation in Bordetella pertussis. AB - By a phenomenon known as phase-variation Bordetella pertussis is capable of changing between a virulent-phase in which multiple virulence-associated determinants are expressed, and an avirulent-phase in which the virulence associated determinants are not expressed. Mutations in the vir locus of B. pertussis have a similar effect. We have examined the state of the vir locus in each of a series of strains derived one from the other by phase-variation. We have found that a single base-pair change is associated with the change between the virulent and avirulent phases. This single base-pair change corresponds to a frameshift mutation in the vir locus. PMID- 2908524 TI - Molecular cloning and analysis of P. 69, a vir-controlled protein from Bordetella pertussis. AB - The cloning sequencing and analysis of an important antigenic component of Bordetella pertussis is described. The gene for P.69, in common with a variety of other so called "virulence" genes, (e.g., adenylate cyclase (AC), pertussis toxin (PT) and filamentous haemagglutinin (FHA)), is under control of the vir locus. The protein P.69 is externally localised on cells and protein preparations are protective as judged by the mouse intra-cerebral challenge test. The gene encoding the P.69 antigen was isolated by hybridization of mixed oligonucleotide probes against B. pertussis genomic DNA. These oligonucleotides were designed from the protein sequence data obtained from a cyanogen bromide digest of the P.69 protein. DNA sequence analysis reveals a G:C rich gene capable of encoding a protein of 910 amino acids and Mr of 93478, whose likely promoter and ribosome binding sites show little homology to their E.coli counterpart. In common with some of the genes in the PT operon the sequence 5'-CCTGG-3' was found 5' to the ATG initiation codon. At the 3', end 29 bases after the TAA stop codon, the sequence 5'GTTTTTCCT-3' was found in an equivalent position to the same sequence in the PT operon. Examination of the protein sequence reveals two regions with directly repeated elements (GGAVP)3(GGFGP)2 and (PQP)5. PMID- 2908525 TI - Bordetella pertussis pilin and pilin-like genes. AB - Bordetella pertussis fimbriae, which mediate the adherence of the microorganism to the epithelium of the respiratory tract, elicit a protective immunogenic response which could be taken advantage of for the creation of an acellular vaccine against pertussis. A few of the fimbrial proteins have been partially characterized by immunological means which recently the cloning and characterization of pilin and pilin-like genes are allowing us to study their structure, regulation of expression during the infectious cycle of Bordetella pertussis, and the basis for antigenic variation. In this communication we will review recent data on Bordetella pertussis pilin and pilin-like genes and their products, with particular emphasis on data most relevant to the design of an acellular vaccine. PMID- 2908526 TI - Bordetella pertussis adenylate cyclase: the gene and the protein. AB - Using the adenylate cyclase-calmodulin interaction as a tool, the B. pertussis cya gene was cloned in a cya defective E. coli strain harbouring a plasmid which expressed high levels of calmodulin. The determination of the nucleotide sequence of the gene showed that adenylate cyclase is synthesized as a large precursor of 1706 amino acids. The calmodulin-stimulated catalytic activity resides in the amino-terminal 400 amino acids whereas the 1300 amino acid carboxy-terminal part of the precursor is endowed with haemolytic activity. The catalytically active 43 kDa form of adenylate cyclase is organized in two domains: the N-terminal domain of 25 kDa harbors the catalytic site, and the 18 kDa C-terminal domain carries the main calmodulin-binding site. Immunological relatedness established between B. pertussis, B. anthracis and rat brain adenylate cyclases suggests a common evolutionary origin of a central domain of these calmodulin-stimulated enzymes. The secretion of the adenylate cyclase-haemolysin bifunctional protein (cyclolysin) requires the expression of three additional genes, contiguous to the cya gene. These four genes appear to form a single operon. The mechanism of secretion of the bifunctional protein should be similar to that described for E. coli alpha-haemolysin. PMID- 2908527 TI - Human T-cell immunity against Bordetella pertussis analyzed at clonal level. AB - Cloned peripheral blood T lymphocytes from an immune donor were grown in interleukin 2 and tested for proliferation in response to inactivated Bordetella species (B. pertussis, B. parapertussis and B. bronchiseptica) and mutants deficient for the expression of virulence-associated antigens. All the T-cell clones obtained were CD4+8- and recognized specifically the Bordetella antigens when presented by autologous B cells. On the basis of the responsiveness to the whole inactivated bacteria, it was possible to cluster the twelve clones obtained into four groups with the following specificity: 1) filamentous hemagglutinin (FHA): 2) B. pertussis specific antigens; 3) virulence-associated Bordetella specific antigens; 4) non-virulence-associated Bordetella specific antigens. Employing two new B. pertussis deletion mutants, clone 6 (representative of cluster 1), was found to recognize the C-terminus of FHA. Furthermore, 3 out of 4 clones of cluster 3 were specifically stimulated by the soluble 69,000 MW protein from the outer membrane of B. pertussis. Surprisingly, none of the twelve clones obtained by stimulation in vitro with whole inactivated bacteria recognized PT. Thus, PT does not seem to be the most representative antigen on the whole inactivated bacteria. However, when a new generation of clones was obtained using soluble PT as the in vitro stimulus, it was observed that 11 clones of this group recognized this antigen. Furthermore, the majority of them was against the subunit S1 of PT. Therefore, we can conclude that a T-cell memory against PT exists in a donor who has had pertussis several years before. In conclusion, these results provide useful information in the attempt to obtain a simplified acellular vaccine for whooping cough. PMID- 2908528 TI - Characterization and clinical study on the acellular pertussis vaccine produced by a combination of column purified pertussis toxin and filamentous hemagglutinin. AB - Bordetella Pertussis Tohama phase I was cultured in a 300-liter fermentor using a medium containing 0.1% heptakis (2,5-0-dimethyl) beta-cyclodextrin (MeCD). Pertussis toxin (PT) and filamentous hamagglutinin (FHA) were purified using affinity and ion exchange gel column chromatographies. Endotoxin contents of these antigens (10 micrograms PN/ml) were less than 10 ngLPS/ml. PT and FHA were independently treated with formalin in the presence of amino acid and were mixed at a protein concentration ratio of 1:4, the same ratio of our commercialized acellular pertussis vaccine. PDT vaccine containing 2 micrograms PN of PT and 8 micrograms PN of FHA per milliliter was prepared. This PDT vaccine satisfied all the items of the Japanese Minimum Requirements including potency and toxicity tests. Even after this vaccine was incubated for 4 weeks at 37 degrees C, no deaths of the inoculated mice were observed after challenge with 4 mg of histamine on the 4th and 12th day of the inoculation. Compared with the conventional vaccine, this new vaccine caused less swelling in the mouse footpad test. A field trial of our two vaccines, one manufactured by the conventional method (lot No. 21A) and the other produced by the new method (lot No. KC8702), revealed that children receiving KC8702 showed almost the same anti-PT and anti FHA antibody levels as those given 21A. Those who received KC8702 suffered from less local side effects such as redness, swelling or induration than those given 21A. Our new method for the production of acellular pertussis vaccine permits us the economical manufacturing of the vaccine with uniform quality in a closed system. PMID- 2908529 TI - Aerosol infection test for evaluation of pertussis vaccine. AB - Evaluation of acellular pertussis vaccine and components of B. pertussis was performed by the use of an in vivo assay system consisting of the mouse aerosol challenge test and the antibody responses in mice. Acellular pertussis vaccine (ACP), pertussis toxin (PT), filamentous hemagglutinin (FHA), fimbriae or whole cell vaccine (WPV) were challenged intrapulmonarily with B. pertussis. The number of colonies of B. pertussis in the lungs of the mice were counted. 1. Does response relationships were observed between the dose of the vaccines, APV or WPV, and B. pertussis colony counts in the lungs of mice injected with one of the vaccines or immunogens. Higher doses of the vaccines or immunogens resulted in reduced numbers of colonies of B. pertussis in the lungs of mice. 2. When the amounts of total protein nitrogen were in the same range, APV and a mixture of PT and FHA showed higher protective efficacy than PT or FHA alone. 3. Rises in antibody titers were observed in mice injected with APV, WPV, PT or FHA. PMID- 2908530 TI - Further characterization of Japanese acellular pertussis vaccine prepared in 1988 by 6 Japanese manufacturers. AB - In 1974, we published a paper entitled "Leukocytosis-Promoting Factor of Bordetella pertussis. Its Identity with Protective Antigen". A preparation which was purified from the culture supernatant of Bordetella pertussis phase I, Tohama strain by consecutive steps of ammonium sulfate fractionation and sucrose density gradient centrifugation showed leukocytosis-promoting, histamine-sensitizing and hemagglutinating activities. The preparation consisted of two proteins: pertussis toxin (PT) and filamentous hemagglutinin (FHA). After treatment with formalin, this preparation elicited strong mouse protective activity. Passive protection tests in mice with the anti-PT and anti-FHA sera also showed that these sera had protective activity. According to these findings, Japanese manufacturers have succeeded in preparing an acellular pertussis vaccine containing PT toxoid and FHA as main protective antigens on a large scale. Acellular pertussis vaccine was introduced in 1981 as purified pertussis vaccine in Japan. Characteristics of this vaccine have been reported elsewhere in the last eight years. Further characterization of Japanese pertussis vaccines which were produced in 1988 by six manufacturers was carried out. There was no fundamental difference among the six products; each vaccine consisted of PT toxoid and FHA as the main protective antigens. PMID- 2908531 TI - Effects of alpha-1 adrenergic blockade on regional flow in the ischemic heart. AB - Although ischemia induces strong coronary vasodilation, some vasoconstrictive tone persists in the ischemic myocardium. To assess whether this tone is mediated through alpha adrenergic receptors, coronary blood flow was measured with radioactive microspheres in the normal and in the ischemic left ventricular wall of the dog before and during alpha blockade with Trimazosin. Ischemia was accomplished by decreasing the coronary perfusion pressure to 22 +/- 1.4 mmHg. Heart rate and aortic pressure were kept constant in each experiment. Trimazosin significantly increased flow in the normal left ventricular wall, but to a greater extent in the subepicardium than in the subendocardium with a decrease of the inner/outer flow ratio from 1.38 +/- 0.12 to 1.20 +/- 0.11 (p less than 0.05). In the ischemic region, Trimazosin did not change total transmural flow, but flow decreased in the subendocardium and increased in the subepicardium with a decrease in the inner/outer flow ratio from 0.63 +/- 0.09 to 0.38 +/- 0.06 (p less than 0.01). These results show that a vasoconstrictive tone mediated through alpha-1 adrenergic receptors persists in the ischemic myocardium, the blockade of which is detrimental for the subendocardium. PMID- 2908532 TI - A rapid procedure for removal of excess linkers. PMID- 2908533 TI - Fitting of a binomial distribution to the number of chiasmata per bivalent. AB - Statistical tests on the distribution of the number of chiasmata per chromosome, collected from literatures, showed that they can be approximated by binomial distributions with one obligatory chiasma, i.e., B(N-1, p). N is proportional to the average number of chiasmata, while p is nearly constant for the species tested. PMID- 2908534 TI - Restriction fragment length polymorphism (RFLP): applications in human chromosome mapping and genetic disease research. PMID- 2908535 TI - [Burning mouth syndrome]. PMID- 2908536 TI - Hereditary factors in Takayasu disease. II. Various blood types. AB - As HLA studies suggest that the genetic factors contributing to the pathogenesis of Takayasu disease may be polygene, various red blood types, allotypes of serum protein and red blood cell enzyme polymorphisms in eighty-four patients with Takayasu disease were studied and their phenotypes and gene frequencies were compared with those in healthy Japanese. Statistically significant high frequencies of phenotypes and/or gene frequencies were confirmed in MNSs, Rh-Hr, Tf, Gc and Pi in Takayasu disease, as compared with those in controls. These characteristics of gene frequencies were more remarkable in patients who do not carry HLA Bw52. These data suggest that the genetic factors contributing to the pathogenesis of Takayasu disease are polygene and may be located in chromosome No. 1, 4 and 14. PMID- 2908537 TI - Restriction fragment length polymorphism of the human C3 complement gene. AB - A cloned gene-specific probe for human complement (C3) was hybridized to DNA samples digested with various restriction endonucleases. The C3 probe detects one restriction fragment length polymorphism (RFLP) that occurs frequently in the French population when DNAs are digested with Sac I. The corresponding DNA alleles can be readily used in linkage analysis of loci on chromosome 19, and such a polymorphism can be followed through myotonic dystrophy families. PMID- 2908538 TI - Association between a 10 kb Pvu II restriction fragment of genomic DNA with the hemochromatosis gene. AB - This study concerns the association between the hemochromatosis susceptibility gene and a 10 kb Pvu II HLA-class I specific restriction fragment. Forty Pvu II fragments are detected after hybridization with A3 or B7 probes, and 20 among them are polymorphic. The 10 kb polymorphic Pvu II fragment correlates absolutely with the A3 serological allele and patients with hemochromatosis, heterozygous or homozygous for A3, have the 10 kb Pvu II band. PMID- 2908539 TI - 500-MHz 1H-n.m.r. and conformational studies of fucosyloligosaccharides recognised by monoclonal antibodies with specificities related to Le(a), Le(b), and SSEA-1. AB - 500-MHz 1H-n.m.r. spectroscopy has been used to examine several fucosylated oligosaccharides in studies to characterise carbohydrate antigenic determinants recognised by monoclonal antibodies. Reduction of the oligosaccharides to give additional variants for analysis showed that oligosaccharides having an alpha-L fucosyl group linked to the reducing end residue have markedly different chemical shifts, and in some instances different antigenic activity, compared to their alditols. This information was incorporated into space filling molecular models of the oligosaccharides in order to predict the topography of atoms recognised by the antibody combining sites. These studies are an intermediate stage in the full characterisation of oligosaccharide conformation and molecular recognition by methods which accurately determine torsional angles and through-space internuclear distances. PMID- 2908540 TI - [Pharmacologic and therapeutic advancements in neurology]. PMID- 2908541 TI - [Prevention and treatment of hypermotive syndromes in patients needing dental care. 2. Treatment]. AB - In the present review the Authors describe the most common therapeutical protocols used in the treatment of the most complex cases of hyperreactivity and various therapeutical instrumental and pharmacological tools now available for the dentist to solve problems linked to hyperemotive patients undergoing odontoiatric therapy. PMID- 2908542 TI - [Incidence of orodental trauma in sports: soccer, water polo and cycling]. AB - The Authors analyze the incidence of the oral-dental traumas during the practise of three different sports: soccer, water polo and cycling, underlining the importance of the use of mouthguard as a specific oral protection. PMID- 2908543 TI - [Subdural empyema: medical treatment]. AB - A young man who initially presented right maxillary sinusopathy which was treated with antibiotics, developed meningeal syndrome in association with focal neurological signs followed by focal tonoclonic convulsions which subsequently became general. Computed tomography confirmed the presence of a left parasagittal and right frontal subdural empyema. Medical treatment with antibiotics, dexamethasone and anticonvulsants resulted in rapid clinical and radiologic improvement in both the sinuses and brain images. The diagnostic and therapeutic aspects are discussed and medical treatment recommended as the first step in the therapy of subdural empyema when there is no other critical neurological situation. PMID- 2908544 TI - [New therapeutic alternatives in Parkinson disease]. PMID- 2908546 TI - The treatment of congestive heart failure with diuretics and nondiuretic agents. PMID- 2908545 TI - [Continuous dopaminergic stimulation in Parkinson disease]. PMID- 2908547 TI - DNA restriction fragment length analysis of the human class II genes (DR,DQ) of bone marrow transplant donor-recipient pairs by DNA-DNA hybridization. PMID- 2908548 TI - RPA-2.10: an anti-CD2 monoclonal antibody that inhibits alloimmune responses and monitors T cell activation. PMID- 2908549 TI - Age-related alteration in the effect of Thy-1 antibody on autorosette formation. PMID- 2908550 TI - Human T cell activation: participation of Tll antigen (CD2, T,gp.50) in T cell accessory cell interactions. PMID- 2908551 TI - Three HLA-DR7 haplotypes defined by DQ specificities and DQ-beta restriction fragment length polymorphisms. PMID- 2908552 TI - A new approach to tissue typing in kidney transplantation: DNA typing. PMID- 2908553 TI - Southern analysis of HLA-DR: molecular cloning of a DR beta chain-specific fragment. PMID- 2908554 TI - Definition of HLA-DQ polymorphisms by RFLP and in serological and cellular assays. PMID- 2908555 TI - Effect of alteration of murine Ir-Thy-1 gene product on anti-Thy-1 response. PMID- 2908556 TI - Evolution and phylogenetic distribution of the specialized isozymes of 3-deoxy-D arabino-heptulosonate 7-phosphate synthase in superfamily-B prokaryotes. AB - Purple sulphur (Superfamily B) bacteria vary greatly in the isozyme number and regulatory properties corresponding to the initial step of aromatic amino acid biosynthesis, 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP) synthase. The signal evolutionary events that are responsible for generation of the three regulatory isozymes of DAHP synthase found in the contemporary Escherichia coli and other enteric bacteria have been deduced, starting from a common ancestor of all Superfamily-B organisms. This analysis of one prokaryotic grouping is a model for analogous studies of the evolutionary history of other biochemical pathways. It is also the beginning of an analysis that can be extended to include the entire assemblage of prokaryotic organisms. PMID- 2908557 TI - The International Commission on yeast and yeast-like microorganisms of the International Union of Microbiological Societies: its conferences and activities. PMID- 2908558 TI - Subunit structure and enzymic activity of pertussis toxin. AB - Pertussis toxin, an ADP-ribosylating toxin, interacts with vertebrate cells of many types and inhibits the ability of these cells to respond to certain hormones and neurotransmitters, resulting in a multitude of biological effects. The structure and mechanism of action of this toxin are described. PMID- 2908559 TI - Insulin and dexamethasone stimulate transcription of an amplified glutamine synthetase gene in Chinese hamster ovary cells. AB - We have investigated the regulation of glutamine synthetase (GS) mRNA synthesis in Chinese hamster ovary cell mutants which overproduce GS and contain an amplified GS gene. Specific mRNA synthesis was analyzed by measuring elongation of transcripts in isolated nuclei. Transcription was assayed by hybridization of newly synthesized [32P]RNA to a genomic GS clone. Nuclear transcript elongation was inhibited more than 90% by alpha-amanitin. The relative rates of GS mRNA synthesis in nuclei from cells incubated for 2 days with no additions, insulin, dexamethasone, or (Bu)2cAMP are 186, 419, 375, and 227 ppm, respectively. The insulin- and dexamethasone-mediated increases in GS transcription rate (2-fold) were associated with 3.7- and 5.8-fold increases in GS mRNA abundance. By contrast, alpha-tubulin gene transcription was not altered by insulin or dexamethasone; however, it was decreased by (Bu)2cAMP. PMID- 2908560 TI - [Treatment of acute pancreatitis with somatostatin and total parenteral nutrition in a chronic uremic patient undergoing hemodialysis]. PMID- 2908561 TI - Magnesium mediated change in physical state of phospholipid modulates membrane ATPase activity. AB - During reconstitution of pig heart mitochondrial H(+)-ATPase in soybean phospholipid liposomes by the cholate dialysis method, Mg2+ greatly enhanced 32Pi ATP exchange activity, ATPase activity and the sensitivity to oligomycin or DCCD of the reconstituted enzyme complex. The effect of Mg2+ on the lipid packing or fluidity of the reconstituted proteoliposomes was measured by means of spin labels, fluorescent probes and pyrene excimer formation efficiency. A difference in fluidity seemed to be localized near the polar faces of lipid bilayers of the reconstituted enzyme complex. Fluidity was less in the presence of Mg2(+) containing and the Mg2(+)-'free' samples. Based on the results obtained a hypothetical scheme was proposed for Mg2(+)-mediated change in the physical state of phospholipid modulates incorporating H(+)-ATPase in liposomes. It postulated that Mg2+ may play a role in altering the lipid fluidity of the bilayers, which would induce a change of conformation of F0 portion (buried in the lipid core) of H(+)-ATPase complex. Such change could be transmitted to the soluble F1 portion, the conformation of which is in turn altered, resulting in higher enzymatic activity. Such an assumption was further supported by the results of a series of biochemical and biophysical experiments. Similar to its effect in the reconstitution of porcine heart mitochondrial H(+)-ATPase in liposomes, Mg2+ may also enhance the enzyme activity of reconstituted cytochrome C oxidase, porcine kidney medulla Na,K-ATPase, Ca-ATPase from rabbit sarcoplasmic reticulum and chloroplast H(+)-ATPase, in liposomes. It may be inferred that the structure and function of many membrane proteins are similarly modulated by Mg2+.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2908562 TI - Magnesium fluxes in ventricular fibrillation and defibrillation in untreated and dibenzepine HC1 pretreated cats. AB - Serum magnesium concentration (S-Mg) was estimated in 12 anesthetized cats before and after central thoracotomy, during an electrically induced ventricular fibrillation (VF) and after defibrillation (DEF), and again, in the same experimental animals, after the administration of 3 mg/kg of dibenzepine HC1--a tricyclic antidepressant reported to facilitate spontaneous DEF--as well as during a subsequently induced VF and after the spontaneous DEF which followed. In the first part of the experiment, the surgery and the induction of VF caused no significant change of mean serum magnesium concentration (S-Mg) or serum calcium concentration (S-Ca), whereas the DEF was accompanied by Mg efflux (a significant increase of mean S-Mg from 0.824 mmol/l, SD 0.182, n = 12 to 0.991 mmol/l, SD 0.182, n = 12; P less than 0.05). In the second part of the experiment, following the administration of dibenzepine HCl there was Mg influx (a lowering of mean S Mg to 0.891 mmol/l, SD 0.160, n = 12; P less than 0.05). During VF in the pretreated cats, S-Mg remained unchanged, while S-Ca decreased significantly (P less than 0.05), followed by a rebound Ca++ efflux (a systematic rise of S-Ca) as the animals defibrilated spontaneously. Concomitantly, there was Mg efflux (a systematic rise of S-MG), the mean S-Mg rising from 0.879 mmol/l, SD 0.143, n = 9 to 1.083 mmol/l, SD 0.257, n = 7, ie to virtually the same value as that obtained after electrically induced DEF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2908563 TI - The International Union Against Cancer (UICC) and its Professional Education Program. AB - The International Union Against Cancer (UICC) is a world federation composed of 242 member organizations. One of its functions is organizing a quadrennial international cancer congress. The next congress will be held in Budapest in August, 1986. Other UICC programs include a Detection and Diagnosis Program, a Tumor Biology Program, a Public Education Campaign, Fellowships and Awards Program, Epidemiology and Prevention Program, Smoking and Cancer Program, Treatment and Rehabilitation Program, and the Professional Education Program. The latter produces a UICC Manual of Clinical Oncology, sponsors regional education meetings, offers consultation visits on request, and offers courses and training programs. The American activities are coordinated by the USA National Committee on the UICC, comprised of representatives of the United States members of the UICC. PMID- 2908564 TI - Serotonin and serotoninergic neurons. A radioautographic and immunocytochemical study of the nucleus raphe dorsalis and nucleus dorsomedialis hypothalami. AB - In an attempt to define cytophysiological criteria with which to establish whether or not a given neuron is serotoninergic, radioautography was combined with serotonin (5-HT) immunocytochemistry on the same sections from the nucleus raphe dorsalis (NRD) and/or nucleus dorsomedialis hypothalami (NDM) in rats subjected to intraventricular administrations of (3H)-5-HT or (3H)-dopamine (DA). All the (3H)-5-HT-accumulating neurons (cell bodies, dendrites and terminals) were found to be distinct from the (3H)-DA labeled ones and invariably immunostained for 5-HT in both regions studied. However, some immunoreactive neuronal elements within the area of tracer diffusion did not exhibit significant radioautographic labeling. In the NDM where 5-HT immunoreactive nerve cells could be detected only after intraventricular administration of 5-HT, these were found to be definitely distinct from the tyrosine hydroxylase immunoreactive and (3H) DA labeled neurons of the dopaminergic periventricular-arcuate complex. After immunostaining for GAD at the electron microscopic level, (3H)-5-HT labeled nerve cells and terminals were not found to exhibit any significant immunoreactivity. Associations between (3H)-DA labeled and GAD immunoreactive processes with 5-HT immunoreactive or (3H)-5-HT-accumulating neurons, respectively, could also be observed in the NDM. When considered as a whole along with previous observations by other authors indicating a probable synthesis of 5-HT within NDM neurons, our data suggest that a given neuron can be classified as serotoninergic on the sole basis of its ability to selectively take up exogenous 5-HT under experimental conditions compatible with non interspecific labeling of catecholaminergic neurons. They also provide valuable information on the neurochemical environment and possible control of central serotoninergic neurons. PMID- 2908565 TI - [Recent contributions concerning the development and distribution of dopaminergic innervation in the cerebral cortex of the rat]. AB - Tyrosine hydroxylase was used as an immunocytochemical marker of dopaminergic axons in the cerebral cortex either in fetuses or in postnatal life after lesion of the noradrenergic input. The lesion was controlled by the absence of dopamine beta-hydroxylase immunoreactivity. Fluorescence histochemistry also allowed the specific visualization of the dopaminergic system following uptake of exogenous amines in tissue sections in presence of selective high affinity transport inhibitors. Two main dopaminergic (DA) subpopulations reach the medial cortex of the rat: 1) a deep one, first detected in the anterior frontal cortex on day 16 of embryonic life, was well developed at birth and extended caudally in layer V and/or layer VI toward the splenium of corpus callosum; 2) a superficial one was detected in layer I of the anterior cingulate cortex (area 24) on postnatal day 3 to 5 and invaded layer III from day 6 to 14. The adult distribution pattern and striking varicose aspect were not reached until day 21 to 30. In addition to these medial fields, a dopaminergic innervation of low density was detected laterally along a dorsal sagittal strip which encompassed several distinct cytoarchitectonic areas in the sensorimotor and visual cortex (medial and lateral agranular field, area 18b) as well as in discrete zones of the retrosplenial granular 29c, b, and agranular 29d areas. Several characteristics of this newly observed DA input were similar to that of the superficial field described in the anterior cingulate cortex; these similarities suggested that the subpopulation of DA neurons which provides projections to the anterior cingulate cortex could also contribute to the motor and visual cortex and thus play a role in sensorimotor integration. A DA terminal field was also demonstrated in the temporal part (ventral and caudal) of the hippocampal formation, the subiculum especially the prosubiculum and the adjacent CA1 hippocampal field being the main targets. This DA terminal field in the hippocampal formation matches with the area which projects toward the accumbens nucleus. Thus, the hippocampo-striatal projections which represent a link of functional importance between the limbic and central motor systems, could be modulated by the dopaminergic meso-cortico-limbic pathway. The predictive values of these data in the ascent of the phylogenetic scale are further considered. PMID- 2908566 TI - [Current directions in the treatment of gastric and duodenal ulcers]. PMID- 2908568 TI - Malignant melanoma: biology, diagnosis, and therapy. PMID- 2908567 TI - Regulation of allied health practitioners. PMID- 2908569 TI - Fine needle aspiration biopsy of metastatic melanoma. PMID- 2908570 TI - Radioimmunoimaging of malignant melanoma with monoclonal antibodies. PMID- 2908571 TI - Flow cytometry in melanoma. PMID- 2908572 TI - Gangliosides as antigens of human melanoma. PMID- 2908573 TI - Randomized trials of heated perfusion of extremity melanoma. PMID- 2908574 TI - Vaccinia virus oncolysates in the treatment of malignant melanoma. PMID- 2908575 TI - Characteristics of cultured human melanocytes from different stages of tumor progression. AB - Based on the clinicopathological delineation of distinct steps of tumor progression in the melanocytic system, the in vitro behavior of melanocytes with increasing malignant potential has been investigated. Tumor progression in melanocytes is characterized by an increasing growth autonomy and decreased requirement but enhanced utilization of exogenously provided polypetide growth factors (EGF, IGF-I). The endogenous production of growth factors such as alpha TGF, PDGF, and bFGF by metastatic melanoma cells might contribute to their independence from exogenously provided factors. Although expression of some melanoma-associated antigens in vivo is detectable only on malignant cells, propagation of normal melanocytes in tissue culture leads to expression of the majority of these antigens. Many of these antigens can be grouped into functionally defined categories, including growth factor receptors, extracellular matrix proteins, and cell-substrate interacting antigens. One cell-substrate interacting antigen, the GD2/GD3 ganglioside, appears to play a critical role in the metastatic process of melanoma cells. The successful propagation and characterization of melanocytic cells of all stages of tumor progression in tissue culture provide a unique human experimental model for the study of mechanisms of malignant transformation. PMID- 2908576 TI - The cytogenetics of human malignant melanoma and premalignant lesions. PMID- 2908577 TI - The Ha-ras-1 oncogene and the molecular genetics of human melanoma. PMID- 2908578 TI - Epidemiologic aspects of intraocular malignant melanoma. PMID- 2908579 TI - Abnormal nevi, excess total nevi, and melanoma: an epidemiologic perspective. PMID- 2908580 TI - Intestinal lumen and mucosal microclimate H+ and NH3 concentrations as factors in the etiology of experimental amebiasis. AB - Axenically cultivated Entamoeba histolytica, trophozoites, strains HM-1:IMSS and HM-38, were suspended in solutions of NaCl, 330 mOsm, of varying pH and ammonium concentrations. Short-term viability was inversely proportional to the ammonia concentration of the medium and was independent of the ammonium concentration and pH. The NH3-induced ameba killing was associated with a cellular alkalosis and cell swelling. While short-term trophozoite viability was unaffected by changes in the medium pH over the range 5.5-8.0, long-term viability was reduced by high pH, and of three pH values tested (6.27, 7.27, and 8.27), trophozoite growth was greatest at the lower value. Chemotaxis was observed in media over the pH range 5.5-8.0, and attenuated chemotaxis was observed in trophozoites in media containing NH3 (0.1 mM). The cecal content total ammonia concentration and pH and the in vivo mucosal microclimate pH were measured in young adult male rats, hamsters, and gerbils. Ceca of the three rodent species were also inoculated with HM-38 trophozoites and 7 days later the cecal contents were studied for signs of amebic infection. Infections were absent in the rat, the species with highest luminal total ammonia concentration and mucosal microclimate pH. All gerbils were infected. This species had the lowest mucosal microclimate pH. The hamster, with the intermediate microclimate pH, had a low infection rate (1 of 5). It is proposed that when ammonium diffuses from the large intestinal lumen into a more basic mucosal microclimate, it is converted to ammonia, and the combination of this ammonia and the high microclimate pH threatens Entamoeba trophozoite viability and reduces the probability of a given ameba penetrating the mucus blanket and invading the mucosal epithelium. PMID- 2908581 TI - Leukocyte subsets in the granulomatous response produced after inoculation with Mycobacterium leprae-BCG in lepromatous patients. AB - Leukocyte subsets present in the granulomatous response produced after the inoculation of a mixture of Mycobacterium leprae and BCG in lepromatous leprosy patients were characterized in situ using monoclonal antibodies and an immunoperoxidase technique. The granuloma produced after M. leprae-BCG inoculation showed a distribution pattern similar to tuberculoid granulomas. T lymphocytes bearing the CD8 phenotype (T cytotoxic/suppressor) were sequestered to the periphery of the epithelioid tubercles and T helper-inducer CD4+ lymphocytes were distributed throughout the infiltrate. Langerhans cells CD1+ were increased in the epidermis, and in dermis they were localized mainly in the mantle surrounding the granuloma. Most of the dermal infiltrate produced after the inoculation or M. leprae-BCG expresses the HLA-DR antigen. Similarly, most keratinocytes were also positive to this MHC antigen. The granulomatous response to BCG was similar to the inoculation of a mixture of M. leprae-BCG, however acid fast bacilla were still present. The inoculation of M. leprae produced a macrophage granuloma with no clearing of the bacilla which resembles the lepromatous leprosy granuloma. PMID- 2908582 TI - Aerosol transmission of Hantaan and related viruses to laboratory rats. AB - Hantaan, Seoul, and Puumala viruses were transmitted to 12-16-week-old female Wistar Rattus norvegicus by inhalation. The rodent infectious dose for each virus by intramuscular inoculation and by inhalation was determined, as was the infectious dose for Vero E-6 cells by direct plaque assay. PMID- 2908583 TI - The management of pain in cancer: a guide to drugs and dosages. AB - Pain is a complex somato-psychic experience, and all pains do not respond equally to opioid analgesics. Muscle and deafferentation pains are best eased by alternative treatments. Bone pain responds best to the combined use of morphine and an NSAID. Nerve compression often necessitates the concurrent use of a corticosteroid. Few patients need neurolytic or neuro-ablative procedures. Opioid use is governed by three key principles: "By the mouth," "by the clock," and "by the ladder." Morphine remains the strong opioid of choice for most patients. Respiratory depression is not a problem, nor is tolerance. Addiction (psychological dependence) does not occur in patients with opioid responsive pains. PMID- 2908584 TI - What nononcologists need to know about MEN IIb. PMID- 2908585 TI - [New beta 2-adrenergic agonist agents]. PMID- 2908586 TI - [Chronic T-lymphocyte lymphatic leukemia. Clinico-pathologic assessment and new epidemiologic data related to cases correlated with HTLV-I in Italy]. PMID- 2908587 TI - Multidrug resistance. AB - The understanding of the mechanism(s) of multidrug resistance has increased at a rapid rate over the past year. Many new inhibitors, new agents equitoxic to MDR and sensitive cells, techniques for screening, and application to therapies will no doubt be within the grasp of the clinical oncologist over the next few years. However, whether in-vitro MDR is synonymous with clinical resistance is still an unanswered question, and other forms of resistance may be co-existing in patient tumors. PMID- 2908588 TI - Multidrug resistance. PMID- 2908589 TI - Influences of the microenvironment on B-cell responses of wasted mice: comparison of Peyer's patches and mesenteric lymph nodes. AB - Wasted mice bear an autosomal recessive mutation (wst/wst) that gives rise to neurologic abnormalities and immunologic deficiency evident as early as 21 days of age. Features of the immune deficiency include absence of plasma cells at mucosal sites, reduction in weight of thymus and spleen relative to body weight, and low serum levels of some immunoglobulin (Ig) isotypes. In these experiments, we have examined parameters of B-cell function in Peyer's patches (PP) and mesenteric lymph nodes (MLN) of wst/wst and age-matched control mice. Our results established the following abnormalities in PP but not MLN of wst/wst mice relative to controls: (1) reduced mitogenic responses to lipopolysaccharide, (2) decreased percentages of Ig+ cells, (3) increased percentages of B-cells bearing large amounts of surface Ig ("very bright" Ig+ cells), and (4) reduced levels of all Ig-specific messenger ribonucleic acids (mRNAs) except alpha-mRNA. The only immunologic abnormality consistently expressed in lymphocytes from both MLN and PP of wst/wst mice is reduced levels of IgA+ B cells and alpha-mRNA. Morphologic studies revealed no consistent abnormalities in lymph nodes, spleens, livers, or PP of wst/wst mice when compared to littermate controls. These results support the idea that some of the immunologic abnormalities reported in wst/wst mice are due to microenvironmental influences. Of the parameters examined in this report, only reduced IgA (mRNA levels and percentage of positive cells) is consistently observed in PP, MLN, and spleen. PMID- 2908590 TI - [Towards a new pharmacology of the synaptic transmission]. PMID- 2908592 TI - Immunologic approaches to the classification and management of lymphomas and leukemias. PMID- 2908591 TI - Somatostatin and glucose homeostasis in liver cirrhosis of the elderly. PMID- 2908593 TI - Immunologic approaches to the classification of lymphomas and lymphoid leukemias. PMID- 2908594 TI - Detection of central nervous system involvement in patients with leukemia or non Hodgkin's lymphoma by immunological marker analysis of cerebrospinal fluid cells. PMID- 2908595 TI - Detection of residual disease in acute leukemia using immunological markers. PMID- 2908596 TI - Radioimmunoscintigraphy of lymphoma with monoclonal antibodies. PMID- 2908597 TI - Radiolabeled antibodies in Hodgkin's disease. PMID- 2908598 TI - Monoclonal antibody therapy of lymphomas and leukemia. PMID- 2908599 TI - Autologous bone marrow transplantation in acute leukemia and lymphoma following ex vivo treatment with monoclonal antibodies and complement. PMID- 2908600 TI - Immunologic approaches to the classification of non-Hodgkin's lymphomas. PMID- 2908601 TI - Endocrine therapies in breast and prostate cancer. PMID- 2908602 TI - Preclinical studies and antitumor mechanism of action of LHRH analogues. PMID- 2908603 TI - Effects of estrogens and antiestrogens on cell proliferation: implications for the treatment of breast cancer. PMID- 2908605 TI - Progestational agents in the treatment of breast cancer. PMID- 2908606 TI - Luteinizing hormone-releasing hormone analogues in the treatment of prostate cancer. PMID- 2908604 TI - Flutamide and other antiandrogens in the treatment of advanced prostatic carcinoma. AB - The various clinical trials suggest that the qualitative and quantitative responses of patients with Stage D prostatic carcinoma to antiandrogens are similar to those achieved with conventional endocrine therapy. These antiandrogens appear generally safe and many avoid the increased risks of cardiovascular or thromboembolic complications seen with estrogen therapy. Further, flutamide appears to have a lesser adverse effect on libido and sexual potency than do alternative therapies. Antiandrogens offer an alternative mode of therapy for previously untreated patients with advanced prostatic cancer but have produced no convincing benefits in hormonally refractory patients. PMID- 2908607 TI - Luteinizing hormone-releasing hormone agonists in the treatment of breast cancer. PMID- 2908608 TI - Aromatase inhibitors as new endocrine therapy for breast cancer. PMID- 2908609 TI - Clinical use of aromatase inhibitors in the treatment of breast cancer. PMID- 2908610 TI - Aminoglutethimide: theoretical considerations and clinical results in advanced prostate cancer. PMID- 2908611 TI - Antiestrogen therapy for breast cancer: current strategies and future prospects. AB - The antiestrogen tamoxifen has had an enormous impact upon the therapy of breast cancer. It is the most widely used antihormonal therapy. The success of tamoxifen has stimulated broader applications of the drug (long-term adjuvant therapy and chemosuppression) and has spurred the development of toremifene, droloxifene, and zindoxifene. However, the clinical evaluation of tamoxifen as a chemosuppressive agent is not sufficiently advanced to be able to provide any conclusion about the success of this strategy. It may be a decade before a randomized clinical study can be analyzed and the value of chemosuppression assessed. In the near future, the clinical evaluation of new antiestrogens will provide additional information about the potential value of these drugs and will perhaps challenge our ideas about the mode of action of antiestrogens as antitumor agents. PMID- 2908612 TI - Microbiological quality of fresh pasta dumplings sold in Bologna and the surrounding district. AB - The microbiological quality of fresh pasta dumplings sold in Bologna and the surrounding district was evaluated. A total of 60 lots (300 subsamples) of fresh pasta dumplings, both 'home-made' and manufactured, were analysed for aerobic plate count (APC), coliforms (total and fecal), Staphylococcus aureus, Clostridium perfringens and Salmonella spp. Thirty one of the 39 lots of 'home made' pasta were found to exceed APC standards and six lots exceeded S. aureus standards. Five (24%) and six (29%) lots of the manufactured pasta were found to be unsatisfactory as regards APC standards and S. aureus standards respectively. The results obtained indicated that a high percentage of samples had a contamination of fecal origin. No Cl. perfringens or Salmonella spp. were found. PMID- 2908613 TI - Medullary carcinoma of the thyroid: differentiating the types and current management. AB - Medullary Ca of the thyroid (MCT) occurs in sporadic and familial form. When familial MCT is associated with pheochromocytoma and parathyroid adenoma or hyperplasia it is called multiple endocrine syndrome type IIa (MEN type IIa). When the syndrome is associated with mucosal neuromata or marfanoid habitus it is called MEN type IIb or type III. When familial MCT is not associated with the above tumors, it is called type IV. Measurement of serum calcitonin is the diagnostic method of choice. CEA is a better prognostic marker than calcitonin. When MCT is confined to the thyroid, total thyroidectomy is recommended. If lymph nodes are involved, lymph node neck dissection is required. I131 therapy and radiotherapy are ineffective. Optimal chemotherapy has not yet been established. PMID- 2908614 TI - Novel routes of opioid administration in the management of cancer pain. AB - Administration of opioids by less conventional routes may produce pain relief of more rapid onset, of longer duration, and fewer side effects in comparison with conventional oral or parenteral administration. This review will discuss the indications, efficacy, complications and potential advantages of these novel routes of administration. PMID- 2908615 TI - [Renal vasculitis: review of the literature and description of a clinical case]. PMID- 2908616 TI - Multiple signals in synaptic communication. Pharmacological and therapeutic relevance. PMID- 2908617 TI - Recent progress in the study of thyroid autoantigens. PMID- 2908618 TI - Immunotoxins. PMID- 2908619 TI - Immunotoxins. Introduction. PMID- 2908620 TI - Toxin structure. PMID- 2908621 TI - Genetic engineering of immunotoxins. PMID- 2908622 TI - Diphtheria-related peptide hormone gene fusions: a molecular genetic approach to chimeric toxin development. AB - There has been considerable effort in chemically conjugating a variety of plant and bacterial toxins to monoclonal antibodies that are directed to surface antigens on target cells. Coupling has been mediated through disulfide linkage, and the resulting conjugates are known generically as immunotoxins. In general, there are a few shortfalls to this approach. For example, since it is clear that not all surface antigens are internalized, one cannot predict the fate of a given IT once bound to its determinant on the surface of a target cell. In addition, in most instances one must activate the amino moiety of lysine residues with a heterobifunctional reagent in order to form disulfide linkage between the ligand and toxophore components. Since the number of reactive groups may be large, the disulfide linked conjugate molecules most likely represent a family of isomeric molecules rather than a defined protein. As a result, one cannot readily manipulate the fine structure of an IT in order to probe the mechanism of toxophore entry into the target cell. The approach that our group has taken toward the development of targeted cytotoxins, however, differs in a fundamental way: Rather than chemically coupling the ligand with toxophore through a disulfide bond, we have turned to genetic engineering in order to create gene fusions whose chimeric products are joined through a peptide bond. Thus, we have genetically constructed a family of fusion genes in which the receptor binding domain of diphtheria toxin has been deleted and replaced with DNAs encoding either alpha-MSH or IL-2. In each instance, it was known that the polypeptide ligand component of the fusion protein bound to specific receptors on target cells and was internalized by receptor mediated endocytosis. We reasoned, therefore, that the substitution of the diphtheria toxin receptor binding domain by these ligands should result in the formation of 'new' toxins whose action should be targeted toward selected eukaryotic cells that expressed either the alpha-MSH or IL-2 receptor. As along as the ligand component was exposed on the surface of the chimeric toxin, the molecule should bind to its receptor and be drawn into the cell by receptor-mediated endocytosis. Since the toxin related/peptide hormone fusion protein is the product of a chimeric gene, it is a single molecular species. This has allowed us to begin to probe by site-directed mutagenesis the structure of fragment B sequences that are required to facilitate the translocation of fragment A across the target cell membrane.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2908623 TI - Immunotoxins containing ricin. PMID- 2908624 TI - Pseudomonas exotoxin--immunotoxins. AB - Monoclonal antibodies can be coupled with PE to make very potent ITs. Two of these ITs (PE-HB21 and OVB-3-PE) have been shown to have antitumor activity in a nude mouse model of ovarian cancer. PE ITs are at least 10-fold more active than the corresponding RTA IT. Deletion analysis of the structural gene of PE has helped assign specific functions to different portions of the molecule. Current efforts are focused on making ITs with recombinant PE. PMID- 2908626 TI - Antibody-toxin conjugation. PMID- 2908625 TI - Immunotoxins containing single-chain ribosome-inactivating proteins. AB - We have summarized what is currently known about the distribution, biological role, and the mechanism of action of the single chain ribosome-inactivating proteins and described the purification of one of them, gelonin, as an example. ITs have been made with several of these proteins and, depending upon the antibody used for conjugation, these immunoconjugates can show specific in vitro cytotoxicity which is similar to that shown by equivalent ITs prepared with ricin A chain. The most potent of these conjugates have shown antitumor efficacy in a variety of animal tumor models, including both syngeneic rodent tumors and xenografts in nude or immunosuppressed mice. An important point needs to be addressed, however, before concluding that ITs containing single chain toxins will be clinically useful. A major problem with this approach is that it is likely that both the antibody and the toxin components of these conjugates will be immunogenic. Both antitoxin and antixenogenic immunoglobulin responses have been shown to occur in animals after infusion of IT, although it has not yet been clearly demonstrated that such antibody responses adversely effect the pharmacokinetics or the efficacy of immunoconjugates. Thus, preliminary enthusiasm over the efficacy of these new reagents must be tempered with the knowledge that their use in the clinic may be limited by the host immune responses or other as yet undefined factors. The fact that there are many immunologically distinct single chain ribosome-inactivating proteins does suggest one way of evading the antitoxin response, by a sequential treatment with a panel of immunoconjugates, each containing a different single chain toxin. PMID- 2908627 TI - Effect of chemical linkage upon the stability and cytotoxic activity of A chain immunotoxins. PMID- 2908628 TI - Structure-activity relationships in diphtheria toxin and Pseudomonas aeruginosa exotoxin A. PMID- 2908629 TI - Immunotoxins: selection of cell-surface antigens and their corresponding monoclonal antibodies. PMID- 2908630 TI - Hormone, lectin and toxin-toxin conjugates. PMID- 2908631 TI - Purification and biochemical characterization of immunotoxins. AB - Written on a plastic bottle of liquid soap in one of our bathrooms (JML) is the phrase 'Absolute cleanliness is next to Godliness!'. Perhaps absolute purity for ITs does not rank so highly, but the availability of purified ITs that contain no nonconjugated antibody or toxin, and no material of very high Mr (aggregates) is essential for a proper comparison of the biological activities of the component proteins with their nonconjugated counterparts. Purified and biochemically well defined ITs make it possible to perform quantitative binding assays, to evaluate receptor-mediated endocytosis and to do cytotoxicity tests in vitro and efficacy studies in vivo, without fear that competition by nonconjugated antibody is affecting the experimental result. This chapter illustrates some of the methods that in combination can be used to purify ITs, including affinity chromatography, gel filtration, and ion-exchange chromatography with buffers of carefully defined composition, using examples from our laboratory to illustrate the procedures. For further details concerning these methods, we would refer the reader to the excellent book by Scopes [40], Purification of Proteins: Principles and Practice, which contains much useful information of both a technical and a practical nature regarding methods for purification of proteins. PMID- 2908632 TI - Immunotoxin enhancers. PMID- 2908633 TI - Enhancement of immunotoxin action: manipulation of the cellular routing of proteins. PMID- 2908634 TI - How protein toxins enter and kill cells. PMID- 2908635 TI - Methods for quantifying immunotoxin efficacy. PMID- 2908636 TI - Kinetic analysis of cytotoxicity. AB - Several variables which influenced the cellular translocation rate of IT have been analyzed in different systems in an effort to improve the efficacy of ITs. Although some conflicting data were reported, several parameters for improving the efficacy of ITs were found: 1) IT was internalized faster when more target antigens were occupied by IT, implying that a highly expressed antigen would be a better target for IT treatment; 2) the nature of the target antigen had an important role in the translocation of IT, presumably directing the IT to different intracellular compartments; 3) small conjugates internalized faster than large conjugates, but the slow translocation of large conjugate was compensated for by adding more toxin molecules to the conjugate; and 4) the kinetics of intoxication by IT was accelerated with certain potentiators, however, in vivo use of these agents may be limited. PMID- 2908637 TI - Isolation and analysis of somatic cell mutants resistant to toxin conjugates. PMID- 2908638 TI - Immunotoxin therapy: assessment by animal models. PMID- 2908639 TI - Prevention of carbohydrate-mediated clearance of ricin-containing immunotoxins by the liver. PMID- 2908640 TI - Human immune response to immunotoxins. PMID- 2908641 TI - Clinical studies: solid tumors. PMID- 2908642 TI - Immunotoxins for ex vivo bone marrow purging in human bone marrow transplantation. PMID- 2908643 TI - Mechanism of action of ricin and related toxins on the inactivation of eukaryotic ribosomes. PMID- 2908644 TI - Toxin selection and modification--overview. PMID- 2908645 TI - Toxin selection and modification: utilization of the A chain of ricin. PMID- 2908646 TI - Human mammary epithelial cells in culture: differentiation and transformation. AB - Large quantities of normal and malignant human mammary epithelial tissues are readily available as surgical discard material. We have developed culture conditions that permit long term, active proliferation of these HMEC in a serum free medium. Thus, large pools HMEC can be stored frozen for repetition of experiments from the same individual's cell population, and for use of the same cell pool by multiple investigators. Of all the specimens that we have thus far examined, we have observed no instances of spontaneous transformation to immortality, nor any karyotypic abnormalities in the cells derived from reduction mammoplasties. However, exposure of normal HMEC to the chemical carcinogen, benzo(a)pyrene did lead to expression of an extended life in culture, and two instances of transformation to immortality. These two established cell lines contain some chromosomal abnormalities, yet retain a relatively stable karyotype upon continued passage in culture. Transformation to malignancy was achieved by exposing these cell lines to tumor viruses and oncogenes. Both the normal HMEC, and the HMEC transformed in vitro, are now being utilized to understand the factors controlling expression of mammary specific properties, response to and production of various growth factors, and the nature of the progressive events leading to malignancy. The maximal usefulness of this, and other human epithelial cell systems, for elucidating the mechanisms of normal and diseased human cellular physiology will require continued efforts to optimize the culture conditions so that they resemble as closely as possible the processes occurring in humans in vivo. PMID- 2908647 TI - Breast cancer: cellular and molecular biology. PMID- 2908648 TI - Control of human breast cancer by estrogen, growth factors, and oncogenes. PMID- 2908649 TI - Actions of pituitary prolactin and insulin-like growth factor II in human breast cancer. PMID- 2908650 TI - Structure and function of the pS2 gene and estrogen receptor in human breast cancer cells. AB - The role of estrogen in the growth of human breast cancers has been investigated at two levels. First, we have studied the pS2 gene, whose transcription is stimulated by estrogen in the human breast cancer cell line, MCF-7. The pS2 gene product is a small, secreted polypeptide currently of unknown function, but with structural features similar to some growth factors. The expression of the pS2 gene has so far been detected only in MCF-7 cells and some breast cancer biopsies. Preliminary studies indicate that pS2 is a potential marker for hormone dependent breast cancer. Ongoing studies will continue to focus on the implicated role of pS2 in the estrogen-mediated growth of breast cancers and its possible use as a marker for estrogen-dependent tumors. Second, we have analyzed the structure and function of the human ER. The receptor stimulates pS2 gene transcription by interacting with an ERE in the 5'-flanking region of that gene. A mutational analysis of the receptor protein has localized a DNA-binding domain, which determines target gene specificity, and a hormone-binding domain. These domains appear to be the only two regions of the receptor which are absolutely required for the transcription-activating function of the ER in transfection assays with reporter plasmids. The N-terminal region of the protein (regions A and B), which is necessary for increasing the efficiency of gene expression using the pS2 ERE, but not a vitellogenin ERE, may also play a role in transcription activation. Further progress in the characterization of the ER functional domains will require studies on target genes in a more physiological chromatin environment, as well as detailed physical analyses of receptor structure. PMID- 2908651 TI - The 52K cathepsin-D of breast cancer: structure, regulation, function and clinical value. PMID- 2908652 TI - Tumor invasion and metastases: biochemical mechanisms. PMID- 2908653 TI - Factors regulating basement membrane invasion by tumor cells. AB - Basement membranes serve as significant barriers to the passage of tumor cells but ones which metastatic cells can pass. This involves the production of a cascade of proteases leading to the activation of a specific collagenase that degrades the unique collagen network in basement membrane. Breast cancer cells, when estrogen dependent, show a requirement for estrogen for invasive activity. However, when these cells progress to an estrogen independent state and increased malignancy, they express an invasive phenotype constitutively. Studies with various anti-estrogens suggest that these responses are mediated via the estrogen receptor. Anti-estrogens lacking agonist activity suppress invasiveness as well as growth of the breast cancer cells. PMID- 2908654 TI - Heterogeneity of genetic alterations in primary human breast tumors. PMID- 2908655 TI - Regulation of development of the normal mammary gland by hormones and growth factors. PMID- 2908656 TI - MMTV as a model for gene expression in mammary tissue. PMID- 2908657 TI - The activation of cellular oncogenes by proviral insertion in murine mammary cancer. PMID- 2908658 TI - Steroid hormone regulation of cultured breast cancer cells. PMID- 2908660 TI - Tumor-associated growth factors in malignant rodent and human mammary epithelial cells. PMID- 2908659 TI - The role of epidermal growth factor in normal and neoplastic growth of mouse mammary epithelial cells. PMID- 2908661 TI - Different mechanisms are responsible for oncogene activation in human mammary neoplasia. PMID- 2908662 TI - Identification of oncogenes in breast tumors and their effects on growth and differentiation. PMID- 2908663 TI - Epidermal growth factor receptors in human breast cancer. PMID- 2908664 TI - The management of the neuropathic bladder in childhood. AB - The key factors in the management of the neuropathic bladder are an understanding of the pathophysiology and natural history of the bladder and urethral dysfunction, an understanding of the urodynamic investigation of such problems, and a realistic approach to treatment. Those children with good motivation, intelligence, mobility and manipulative skills can almost always be made continent by surgical means. Management otherwise is to control or contain incontinence as far as possible and to preserve upper tract function. PMID- 2908666 TI - [Nutritional goals and food guides in Latin America. Basis for their development. Workshop held in Caracas, Venezuela, November 22-28, 1987. Proceedings]. PMID- 2908665 TI - Effect of captopril in Takayasu's arteritis. PMID- 2908667 TI - Three proton-pumping ATPases in yeast. AB - Yeast cells contain three distinct proton-pumping ATPases associated with the mitochondrial, vacuolar or plasma membranes. This review discusses their respective structure and function. PMID- 2908668 TI - [Intra-abdominal cryptorchism. Our experience with 4 testicular autotransplantations]. PMID- 2908669 TI - The 7th International Congress of Pediatric Nephrology. September 7-12, 1986, Tokyo, Japan. Abstracts. PMID- 2908671 TI - International symposium on hereditary nephropathies. 6-8 October 1986, Heidelberg, Federal Republic of Germany. PMID- 2908672 TI - Anderson-Fabry disease--family linkage studies using two polymorphic X-linked DNA probes. AB - Anderson-Fabry disease is an X-linked lysosomal storage disorder due to alpha galactosidase A deficiency. In affected males there is a high mortality in early adult life due to renal failure and cardiovascular complications. We describe our preliminary results from genetic linkage studies in five families using two polymorphic DNA probes, DXS17 and DXYS1, mapping to an area on the long arm of the X chromosome between Xq13-22. DXS17 identified a Taql polymorphism closely linked to the disease locus in three families (lodmax Z = 4.23. at a recombination fraction decreases theta = 0.0). Restriction fragment length polymorphisms detected by DXYS1 were not linked. PMID- 2908670 TI - Prolonged survival in a child with renovascular hypertension from abdominal pulmonary Takayasu's arteritis. AB - Takayasu's disease is an inflammatory condition of the large arteries which comprises circulation to the head, extremities, and, less often, the abdominal viscera or lungs. A 10-year-old girl with renovascular hypertension secondary to Takayasu's arteritis has been followed for over 5 years. Her course is unusual in that (1) her disease is not related to tuberculosis; and (2) despite a persistently active disease course, she has been allowed to experience a fairly normal life-style through continued, extensive medical and surgical management. Vascular involvement has been documented by digital subtraction angiography; less invasive techniques were not useful for monitoring disease progression. PMID- 2908673 TI - XXIst annual meeting of the European Society for Paediatric Nephrology. Budapest, Hungary, September 3-5, 1987. Abstracts. PMID- 2908674 TI - Therapy of pemphigus. PMID- 2908675 TI - Treatment of pruritus. PMID- 2908676 TI - Recent preclinical studies on neurotransmitter function after ECS. PMID- 2908677 TI - Benzodiazepine dependence, withdrawal severity, and clinical outcome: effects of personality. PMID- 2908678 TI - Associations between Alzheimer's disease and RFLPs at the human amyloid beta protein gene locus. PMID- 2908679 TI - [New classes of drugs in psychiatry]. PMID- 2908680 TI - The AIDS paradox. PMID- 2908681 TI - AIDS and the single cell. PMID- 2908682 TI - Neurotransmitter and neuromodulator systems involved in vestibular compensation. PMID- 2908683 TI - [Ultrastructure of the normal vestibular end organ of the guinea pig]. PMID- 2908684 TI - Thyrotropin binding inhibiting antibody (TBIAb) in Graves' disease. PMID- 2908685 TI - [Determination of sublymphocyte basophilic cell in the nasal mucosa in patients with catarrhal maxillary sinusitis]. PMID- 2908686 TI - [Use of trazodone for postoperative pain]. PMID- 2908687 TI - Abstracts of the IV Biennial Winter Workshop on Schizophrenia. Badgastein, Austria, January 24-29, 1988. PMID- 2908688 TI - [Structure and function of human transplantation antigens]. AB - Human transplantation antigens encoded in the major histocompatibility complex (MHC) region play a key role in regulating the immune responses. Here, we will describe the summary of our analyses on the structure and function of the human MHC molecules, HLA antigens as follows. 1) The genomic organization of the HLA antigen region was examined by cosmid cloning and pulsed-field gel electrophoresis technique. The HLA antigen region spans over at least 3,000 kb, and constitutes a multigene family. 2) Genetic polymorphisms in the HLA gene region were analyzed by Southern hybridization with restriction endonuclease digested genomic DNA using the class II cDNAs as probes (RFLP) and found to be tightly associated with each allo specificity. 3) The functional expression of the HLA class II gene product were observed after transfer of their cloned genes into the mouse fibroblast and human lymphocytes. 4) Narcolepsy is completely associated with HLA-DR2 Dw2, but no difference in the sequence of the DQ beta 1 domain could be found between narcoleptic and healthy individuals. This fact suggests that narcolepsy is not caused by mutation in the DQ beta gene. Based on results, it was inferred that one or both of the two Asps within the second variable region in the first domain of the DR beta chain is directly correlated with predisposition to narcolepsy. PMID- 2908689 TI - 2nd Cardiovascular Pharmacotherapy International Symposium. October 18-22, 1987. Abstracts. PMID- 2908690 TI - Residues of some veterinary drugs in animals and foods. Joint FAO/WHO Expert Committee on Food Additives. PMID- 2908691 TI - Study of 47 DNA markers in five populations from four continents. AB - Forty seven DNA markers from 30 genes or chromosomal regions were investigated in five populations (Biaka and Mbuti Pygmies, Melanesians, Chinese and Caucasoids). Both the variation between populations (measured by FST) and between markers is highly significant. The average heterozygosity for all markers is .284 and the average FST is .145. There was no significant difference in the FST values, or in the average heterozygosity between known genes and random segments. The FST distance between all populations considered in pairs, and averaged over all loci favours a primary split between Eurasia and Africa, but this conclusion is neither statistically significant nor uncomplicated. Condensing the 47 markers into 30 "genes" where 10 were treated as haplotypes, it was found that the haplotypes always give higher FST's than the separate markers, although similar conclusions can be drawn. PMID- 2908692 TI - The p12f2/TaqI Y-specific polymorphism in three groups of Italians and in a sample of Senegalese. AB - The TaqI/p12f2 Y-specific RFLP was studied in 258 Italians (69 from North, 74 from Centre-South and 115 from Southern Sardinia) and in 65 Senegalese. The two allelic fragments of 10 and 8 kb characterizing this polymorphism were both found in the Italians but only the 10 kb band was found among the Senegalese. The observed frequency of the 8 kb allele was 32.4% in Central-Southern Italians, 17.4% in Northern Italians and 13.0% in Southern Sardinians. The last figure is significantly lower than that (34.3%) previously reported for a smaller sample of the same population. PMID- 2908693 TI - Restriction fragment length polymorphisms on the X chromosome in populations from Papua New Guinea, Thailand, northwestern Australia and China. AB - Allele frequencies for five polymorphic DNA sequences on the human X chromosome were established for four non-European populations, Australian Aborigines, Papua New Guineans, Thais and Han Chinese. The frequencies were used for genetic distance analysis which in general confirms the patterns found using other polymorphisms. PMID- 2908694 TI - [The incidence of amebiasis in abortion]. PMID- 2908695 TI - The Thy-1 glycoprotein: a three-dimensional model. PMID- 2908696 TI - The scrapie agent and the prion hypothesis. PMID- 2908697 TI - Effect of direct stimulation of renal nerves on urinary sodium and potassium excretion in rat. PMID- 2908698 TI - Electrophysiological effects mediated by the stimulation of cardiac beta 2 adrenoceptors with tulobuterol. AB - We studied the electrophysiological effects of the specific beta 2-agonist tulobuterol in the guinea-pig sinus node and in sheep cardiac Purkinje fibers. Stimulation of beta 2-adrenoceptors by tulobuterol resulted in a slight increase in the rate of firing of the sinus node. In Purkinje fibers, however, automaticity was not affected up to concentrations of 10(-6) M. Consistently, tulobuterol (10(-8)-10(-6) M) did not affect the pacemaker current studied under voltage-clamp conditions. In the same range of concentrations (10(-8)-10(-6)M) tulobuterol dose-dependently increased the contractile force of driven Purkinje fibers. Tulobuterol, at a very high concentration (10(-5) M), had membrane depressant effects as demonstrated by the block of automaticity induced in the spontaneously beating Purkinje fibers and by the reduction of the maximum rate of depolarization in driven preparations. Our results suggest that stimulation of beta 2-adrenoceptors with tulobuterol in sheep Purkinje fibers is associated with an inotropic rather than a chronotropic effect. On the whole, the data confirm the lack of cardiac side effects of tulobuterol. PMID- 2908699 TI - Angiotensin-converting enzyme inhibitors for cardiovascular therapy: recent advances at the Tenth World Congress of Cardiology Washington DC, September 14 19, 1986. PMID- 2908700 TI - Effect of propranolol on ventricular repolarization and refractoriness: role of beta-blockade versus direct membrane effects. AB - The purpose of this study was to define the role of beta-adrenergic blockade and direct membrane effects in the ability of dl-propranolol to alter ventricular repolarization and refractoriness in the intact heart. The effective refractory period (ERP) and the local Q-T interval were measured at an epicardial site in the left ventricle in 14 open-chest dogs anesthetized with alpha-chloralose. Beta adrenergic influences were eliminated in seven dogs (group 1) by stellate transection and nadolol (0.5 mg/kg IV), and enhanced in seven dogs (group 2) by stellate transection and stimulation of the left ansae subclavia. Each dog received an initial beta-blocking dose of propranolol (0.5 mg/kg) followed by a second, cumulative dose of 5.0 mg/kg. In group 1 dogs, there was no significant change in either the ERP or local Q-T interval in response to the first dose of propranolol. In group 2 dogs, left stellate stimulation significantly shortened the ERP (20 +/- 2 msec) and the local Q-T interval (17 +/- 4 msec). The first dose of propranolol prolonged these parameters to values not different from prestimulation control values. There was no change in the H-V interval, QRS complex duration, or diastolic threshold (DT) in either group after the initial propranolol dose. The second dose of propranolol significantly shortened the ERP (5 +/- 1 msec) and the local Q-T interval (11 +/- 2 msec) in both groups. This dose also significantly increased the DT, H-V interval, and QRS complex duration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2908701 TI - Pharmacologic treatment of hypertrophic cardiomyopathy: beta-blockade or calcium blockade or what? PMID- 2908702 TI - [Endocrine pathology frequently associated with sterility. Summarizing studies]. PMID- 2908703 TI - Task-related EEG alpha asymmetry in schizophrenic patients prior to and after neuroleptic treatment. AB - EEG was recorded from bilateral frontal, central, temporal, and parietal leads (referenced to or transformed to a vertex reference) during cognitive activity in 13 normal controls, ten schizophrenics, and eight patients with affective disorders. All subjects were male and right-handed, and patients had been free of psychotropic medications for at least 2 weeks. A verbal (copying text) and spatial (copying shapes) task were matched for stimulus presentation and motor output. The number and rate of correct responses were recorded for each normal subject and 11 of the patients. As reported by others, normal subjects manifested a significant difference in alpha asymmetry between the tasks, reflecting relatively greater alpha suppression over the left hemisphere during the verbal task compared to the spatial task (P less than 0.05). This effect was not significant in either patient group. However, analysis of seven schizophrenics after neuroleptic treatment revealed robust effects of task on alpha asymmetry similar to that present in the normal control group (P less than 0.02). The results suggest that abnormal task-related brain lateralization may be present in untreated schizophrenic patients, but it is state dependent and does not reflect permanent patterns of brain organization. PMID- 2908704 TI - Addition of reserpine to ongoing neuroleptic exposure in chronic schizophrenia. PMID- 2908705 TI - An open study of zuclopenthixol acetate in Viscoleo in patients with acute psychoses. PMID- 2908706 TI - Neuropeptide-dopamine interactions. III. Cyclo(His-Pro) and persistence of dopaminergic supersensitivity on withdrawal from one year continuous neuroleptic treatment. AB - When rats are given dopaminergic antagonists (neuroleptics) continuously for several days behavioral supersensitivity to dopaminergic agonists results. This supersensitivity, however, declines rapidly on neuroleptic withdrawal. The data presented here, however, are the first to show that the supersensitivity persists for a longer duration (greater than 100 days) if the neuroleptic is administered continuously for 1 year. Oral administration of 0.76 +/- 0.13 mg/kg/day cyclo(His Pro), a peptide exhibiting dopaminergic agonist-like properties, during neuroleptic withdrawal did not change the course of dopaminergic supersensitivity reversal. PMID- 2908707 TI - Introduction to the focussed section on molecular and cellular biology in hypertension. PMID- 2908708 TI - Comparative study of the effects of acebutolol, atenolol, d-propranolol and dl, propranolol on the alterations in energy metabolism caused by ischemia and reperfusion: a 31P NMR study on the isolated rat heart. AB - 31-P NMR spectroscopy data recorded for the isolated heart were analyzed, in conjunction with functional and biochemical variables, in order to investigate the effect observed for several different beta-adrenoceptor antagonists or the alterations provoked by global partial ischemia (37 degrees C, 24 minutes, 1% residual coronary flow) and reperfusion in the metabolism of the myocardium. During ischemia: intracellular acidosis, adenosine triphosphate (ATP) degradation, and inorganic phosphate (Pi) accumulation were found to be reduced whether the perfusion fluid contained: acebutolol 2.7 x 10(-5) M, atenolol 10(-5) M, d-propranolol 10(-5) M, or dl-propranolol 10(-5) M. On reperfusion metabolic and functional variables were variously affected by the different drugs, except the Pi level which was, in all series, significantly lower compared with control hearts. The adenylate charge and the glycogen stores were protected in the acebutolol, dl-propranolol, and d-propranolol groups. The ATP level was higher than in controls only in the acebutolol and atenolol groups. The intracellular pH recovered to values nonsignificantly different from preischemic values in the acebutolol and dl-propranolol-treated hearts only. The mechanical performance, expressed as the rate-pressure product, was unaltered by the ischemia-reperfusion sequence in the acebutolol and d-propranolol series, while decreasing significantly in controls and in the atenolol group. In dl-propranolol-treated hearts the mechanical activity, which in normoxic conditions was already halved during the effect of the drug, remained at this same level after ischemia. From these observations, it appears that the nonspecific properties of the drugs, as distinct from beta-blockade, play an important part in attenuating the ischemia induced alteration in myocardial metabolism. Thus, it can be postulated that (1) the metabolic effects of dl-propranolol probably result largely from the reduction of heart work induced by this drug; (2) the maintenance of energy metabolism associated with the preservation of the myocardial activity, as observed in the case of acebutolol and d-propranolol, is possibly a consequence of the existence of a membrane-stabilizing activity. PMID- 2908709 TI - Left ventricular function and beta-blockers: does intrinsic sympathomimetic activity have any influence during chronic therapy? AB - A study comparing the chronic effects of propranolol (n = 21) and pindolol (n = 19) on male patients with stable angina pectoris was performed. Left ventricular function was assessed by serial radionuclide ventriculography. Radionuclide ventriculography was performed at rest and during cold pressor test. Both drugs improved symptoms of angina pectoris by at least one division of the New York Heart Association classification. Cold pressor testing caused increases in heart rate and blood pressure in both groups throughout the study. At rest, pretreatment ejection fraction was similar in both groups. During propranolol treatment this rose sequentially from 49% to 55% at 26 weeks. No change in the resting ejection fraction occurred in those taking pindolol. The difference in response between the groups reached significance at 26 weeks. In those with subnormal left ventricular ejection fraction (less than 50%), resting ejection fraction improved significantly throughout treatment with propranolol rising from a basal value of 39% to 51% at 26 weeks. In comparison, pindolol caused no significant change. There is no apparent advantage to intrinsic sympathomimetic activity in terms of preservation or improvement of left ventricular performance in patients with stable angina pectoris prescribed beta-blockers for extended periods of time. PMID- 2908710 TI - The role of beta-receptor and calcium-entry-blocking agents in acute myocardial infarction in the thrombolytic era: can the results of thrombolytic reperfusion be enhanced? PMID- 2908711 TI - Recent advances in hypertension: 12th scientific meeting of the International Society of Hypertension, Kyoto, Japan, May 22-26, 1988. PMID- 2908712 TI - The effects of intravenous nifedipine on cardiac hemodynamics and contractility in patients with coronary artery disease in the presence or absence of beta adrenergic blockade. AB - We studied the acute effects of intravenous nifedipine on hemodynamics and left ventricular function of CAD patients without previous treatment (group 1) and of 10 CAD patients receiving acebutolol (9 mg/kg daily) and who had been shown to be adequately beta blocked (reduction in heart rate by 25%) (group 2). Intravenous nifedipine (15 micrograms/kg) significantly reduced systemic peripheral resistances in both groups: this was associated with decreased systolic blood pressure and increased left ventricular cardiac output with a slight nonsignificant increase of ejection fraction. There was a significant increase in heart rate in both groups, the chronotropic response to nifedipine being attenuated in patients receiving acebutolol. Left ventricular end-diastolic pressure did not change in the first group, but it was significantly decreased in the second group, with a concomitant increase of end-diastolic left ventricular volume, suggesting an amelioration of diastolic compliance. The effect of nifedipine on intrinsic myocardial contractility was quite different, depending on the presence of beta adrenergic blockade. When given to patients of group 1, nifedipine significantly increased dP/dtmax, Vcemax, and Vmaxd. The same indices, however, were significantly depressed when nifedipine was given to the patients of group 2 receiving acebutolol. This study shows that intravenous nifedipine can be usefully administered to patients with coronary artery disease who have been on adequate beta-blocking doses of acebutolol with relative safety. Under these conditions nifedipine increases cardiac output in association with arterial dilation, despite evidence for a negative inotropic effect. These data also suggest that such an intrinsic negative inotropic effect would normally be masked by compensatory sympathetic activity. PMID- 2908713 TI - Effect of calcium entry blockers on blood pressure and vasoconstrictor responses to alpha-1 adrenoceptor stimulation in conscious spontaneously hypertensive rats. AB - In order to investigate whether vascular alpha-1 adrenoceptor antagonism plays a role in the antihypertensive effect of verapamil, tiapamil, and nifedipine, we studied their potencies to inhibit K(+)-induced 45Ca2+ influx in rat isolated aorta and [3H]prazosin binding in rat brain membranes in vitro as well as their antihypertensive effect and functional alpha-1 adrenoceptor blockade in conscious spontaneously hypertensive rats (SHR) in vivo. Tiapamil proved 70 times less potent than verapamil in inhibiting calcium influx, but was equipotent in displacing [3H]prazosin. Nifedipine proved 10 times more potent than verapamil as calcium channel blocker but displayed negligible affinity for alpha-1 adrenoceptors in vitro. In conscious SHR, the three calcium channel blockers dose dependently reduced mean arterial pressure after oral administration. Only at maximal anti-hypertensive doses, the increases in diastolic pressure to intravenous injection of the selective alpha-1 adrenoceptor agonist cirazoline were temporarily suppressed by nifedipine, verapamil, and tiapamil. No relationship existed between the relative potencies as calcium channel blocker and affinities for alpha-1 adrenoceptor binding sites in vitro with functional vascular alpha-1 adrenoceptor blockade in vivo. The data do not support the hypothesis that vascular alpha-1 adrenoceptor blockade plays a significant role in the anti-hypertensive effect of verapamil and related calcium channel blockers. PMID- 2908714 TI - Calcium antagonists--adverse drug interactions. AB - In the clinical management of heart disease, calcium channel blockers are generally prescribed in combination with one or more anti-angina, antiarrhythmic, or antihypertensive agents. Two different mechanisms are involved in drug interactions: pharmacokinetic and pharmacodynamic. In the former, the disposition of one drug is altered by the action of another, causing an increase or decrease in its absorption or its modified distribution, metabolism, or excretion. In pharmacodynamic interactions, the physiologic effects of one drug interfere either directly or indirectly with those of another, for instance, by alterations in fluid or electrolyte balance. This effect may be antagonistic or additive. The present work outlines the possible adverse interactions between the three main calcium antagonists and other therapeutic agents, including digoxin, beta blockers and antiarrhythmic, anesthetic, antihypertensive, antiasthmatic, and antidiabetic drugs and contrast media. Knowledge of these effects is of major clinical importance in the treatment of cardiac patients. PMID- 2908715 TI - Hemodynamic responses to different levels of alpha-adrenergic interruption in congestive heart failure. AB - The effects of prazosin, clonidine, and indoramin on central and regional hemodynamic parameters and left ventricular performance were analyzed in a congestive heart failure population to compare the pharmacodynamic responses to different levels of alpha-adrenergic interruption in this condition. The sympathetic nervous system is blocked at the peripheral alpha1-receptor by prazosin, at central nervous system alpha-receptor sites (via alpha-adrenoceptor agonism) by clonidine, and at peripheral and central sites by indoramin. Prazosin and indoramin produced reductions in total systemic and pulmonary vascular resistances, mean systemic and pulmonary artery pressures, and pulmonary capillary wedge pressure with little change in heart rate. Both agents selectively increased hepatic blood flow. Clonidine also decreased pulmonary artery pressure and vascular resistance, but evoked negative inotropic and chronotropic activity and did not alter regional blood flow. In contrast to prazosin, indoramin and clonidine did not augment cardiac output or stroke volume. In the setting of congestive heart failure, the central and regional hemodynamic effects and the responses in left ventricular performance vary considerably depending on the site of alpha-adrenergic interruption. PMID- 2908717 TI - Modern concepts in the treatment of ischemic heart disease. Symposium held in Munich, West Germany, November 27-28, 1986. Proceedings. PMID- 2908716 TI - Effect on resting blood pressure and blood pressure homeostasis of short-term administration of the alpha 1-adrenergic receptor antagonist, trimazosin, in hypertension. AB - The effects of trimazosin on blood pressure and cardiovascular homeostasis were studied in 12 subjects with untreated essential hypertension of mild or moderate degree. After a 3-day placebo period, the subjects were given trimazosin at the dose of 50, 100, or 200 mg twice daily (7 am and 7 pm) according to a randomized, double-blind crossover protocol. Each treatment was prolonged for 3 days and separated from the subsequent treatment by a 2-day placebo period. Blood pressure (sphygmomanometry) and heart rate were measured at rest during various laboratory maneuvers on the first and third day of the initial placebo, on the first and third day of the drug periods, and on the second day of the intervening placebo periods. Compared to placebo values, trimazosin caused a reduction in systolic and diastolic blood pressure which was well sustained through the time between the morning and the evening administration of the drug and was accompanied by only a slight tachycardia. the antihypertensive effect was similar in the supine and upright position and in both instances it was greater for the 100 or 200 mg twice daily dose than for the 50-mg twice daily dose. The pressor and tachycardic responses to cold pressor test and to isometric and dynamic exercise were unaffected by the various doses of trimazosin whose antihypertensive effect was therefore similarly evident at rest and during behaviorally occurring blood pressure rises.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2908718 TI - According to MIAMI and ISIS-I trials, can a general recommendation be given for beta blockers in acute myocardial infarction? AB - The goal of early intervention of acute coronary occlusion by beta blockers is to reduce ultimate infarct size and to consequently reduce morbidity and mortality. Until 1986 small early intervention trials suggested that infarct size may be reduced by 25% if treatment was started within 6 to 10 hours after the onset of symptoms. At this time, an average of 80% of the infarct is fully developed. On the basis of previous trials, the reduction of infarct size has been associated with improvement of symptoms, prevention of infarct development, reduced occurrence of arrhythmias and reinfarctions, and earlier discharge from the hospital. Although the trials suggested some benefit in mortality, this issue has not been solved. The MIAMI trial randomized 5778 patients to blind treatment with metoprolol or placebo. ISIS-I randomized 16,027 patients to atenolol with an open label. No titration of the effect on lowering myocardial oxygen requirement was attempted. Both studies included less than 25% of all eligible patients. Exclusions were chiefly due to current beta blocker or calcium blocker treatment. Thus, the results obtained concern only a selected group of patients. In MIAMI only 15% received treatment within 6 hours, while in ISIS 38% were treated within 4 hours. It is therefore likely that in most patients the infarcts were completed before intervention was started. Thus, the two trials did not differentiate between primary and secondary effects on the acute myocardial infarct. Mortality was reduced by 13% (NS) and 15% (p less than 0.04), respectively, in MIAMI and ISIS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2908719 TI - Secondary prevention after myocardial infarction: effects of beta blocking agents and calcium antagonists. AB - Therapeutic interventions in patients with myocardial infarction, whether during the first hours after coronary occlusion or several days later, aim to reduce mortality and morbidity by several mechanisms: Prevention of fatal ventricular fibrillation, limitation of infarct size, and inhibition of platelet aggregation are some examples of such mechanisms. Results from early intervention trials with beta blocking agents, particularly from ISIS-I, suggest that 1-year mortality is significantly lower in selected patients randomized to active treatment. Late intervention studies also suggest a significant reduction in coronary mortality and morbidity with beta blockade, particularly when data are pooled. Studies with the calcium channel blockers nifedipine and verapamil were unable to demonstrate any beneficial effects of these drugs on mortality or reinfarction. In this review article, attention will be directed to the most recent information about the preventive value of beta adrenergic blocking drugs and slow calcium channel inhibitors. PMID- 2908720 TI - Hemodynamic effects of celiprolol at rest and during exercise; a comparison with enalapril. AB - The antihypertensive effects of once-daily administration of celiprolol 400 mg were compared with those of once-daily enalapril 20 mg in 20 mild to moderate essential hypertensives in a single-blind study in which the subjects were randomized to 2 weeks' treatment with either drug, preceded by 2 weeks of placebo administration. Supine and standing systolic blood pressure (SBP), diastolic pressure (DBP), and heart rate (HR) were measured at rest and during exercise (exercise bicycle with increasing work loads up to 100 watts) at the end of either period, 20 to 24 hr after drug or placebo administration. Compared to placebo, both celiprolol and enalapril reduced resting supine and standing SBP and DBP to a marked and similar extent; resting HR was unaffected by enalapril, while celiprolol produced modest reductions. During exercise, however, celiprolol significantly attenuated rises in SBP and HR, while enalapril did not. Indexes of cardiac function at rest obtained by echocardiography and systolic time intervals were unaffected by either drug. Thus, despite similar reductions by both drugs in resting blood pressures, celiprolol produced better antihypertensive effects during exercise than enalapril. PMID- 2908721 TI - Comparison of the effects of acute and chronic beta-blockade on infarct size in the dog after circumflex occlusion. AB - In order to compare the effects of acute and chronic beta-blockade on infact size, the left circumflex coronary artery was occluded for 6 hours in 33 anesthetized dogs. The dogs (18 to 22 kg) were divided into three groups; group 1 (N = 10) served as controls, group 2 received intravenous nadolol (average dose 1.25 mg/kg) just prior to coronary occlusion, and group 3 received oral nadolol (80 mg) twice daily for 16 days prior to coronary occlusion. To ensure equivalent degrees of beta-blockade at the time of occlusion, group 2 and 3 dogs were given incremental doses of intravenous nadolol to abolish the chronotropic response to isoproterenol (2 mu/kg IV). Left ventricular pressure, its first derivative (dP/dt), and heart rate were monitored. The anatomic risk region was determined antemortem by Evan's blue staining while the infarct zone was delineated postmortem by tetrazolium staining. Compared to Group 1, heart rate was 22% lower in group 2 and 15% lower in group 3 dogs 6 hours after occlusion (p less than 0.05). There were no differences among groups in peak left ventricular systolic pressure or mean arterial pressure. Infarct size as a function of the area at risk was 68 +/- 3% in group 1, 52 +/- 7% in group 2, and 44 +/- 8% in group 3. A significant difference was found only between groups 3 and 1. The data suggest that chronic beta-blockade provides greater protection against ischemic-induced necrosis than does acute beta-blockade. The greater protective effect of chronic beta-blockade may be due to chronic adaptive changes in either blood flow or metabolism. PMID- 2908722 TI - T-1583 and forskolin are similar in their cardiac effects and dissimilar in their vascular effects. AB - The cardiac and coronary vascular effects of T-1583, a selective beta 1 adrenoceptor full agonist, and forskolin, a direct activator of adenylate cyclase, were compared in isolated, blood-perfused papillary muscle, sinoatrial node, and atrioventricular (AV) node preparations of dogs. Both agents were injected intra-arterially. The two agents increased the force of contraction of the paced papillary muscle and the unpaced one, and the rate of automaticity of the latter. They increased sinus rate and accelerated AV nodal conduction. In producing these effects T-1583 was 50 to 80 times more potent than forskolin, indicating that both agents have similar cardiac profiles. At the doses that produced a 50% increase in the force of contraction of the papillary muscle, both agents produced about a 20% increase in sinus rate. Such degrees of force-rate separation were close to those obtained with most new positive inotropic agents with an inhibitory action on cyclic AMP phosphodiesterase. T-1583 differed distinctly from forskolin in that the former increased only slightly coronary blood flow, whereas the latter increased it greatly. Thus, forskolin is more coronary vasodilatory than positively inotropic, and more positively inotropic than positively chronotropic. T-1583 is a more positively inotropic than positively chronotropic and more positively chronotropic than coronary vasodilatory. PMID- 2908723 TI - HpaI polymorphism and the sickle gene in Nigerians. AB - The HpaI restriction fragment length polymorphism linked to the beta globin gene was studied in 181 Nigerian subjects. The beta s gene was found in the 13 kilobase (kb) HpaI fragment in 98.4 percent and in the remaining 1.6 percent of the cases in the HpaI 7.6 kb fragment. The majority of beta A genes (94.2%) were found in either the 7.6 or the 7.0 kb fragment whilst the remainders (5.8%) were in the 13.0 kb fragment. The rare, but not zero, associations of beta A with the 13 kb linkage and of beta s genes with the 7.6 kb fragment would lessen the accuracy in the prenatal diagnosis of sickle cell anaemia in this population through the use of the HpaI polymorphism. PMID- 2908724 TI - Synaptic organization of dopaminergic interplexiform cells in the goldfish retina. AB - The synaptic organization of dopaminergic interplexiform cells (DA-IPC) in the goldfish retina was studied by a combined double-label electron-microscopical (EM) immunocytochemical/autoradiographical study. DA-IPCs were labeled with antisera against tyrosine hydroxylase. The possibility of synaptic contact with GABAergic amacrine cells in the proximal inner plexiform layer (IPL) was studied by using 3H-GABA uptake. Most synaptic input and output from DA-IPC processes involved amacrine cell processes. In addition, synaptic interactions were observed between DA-IPC processes and bipolar cell terminals, other DA-IPC processes, very small dendrites in the IPL, ganglion cell and optic fiber layers (OFL), and cell bodies in the ganglion cell layer (GCL). Input and output synapses with GABAergic amacrine processes also were observed. Two-thirds of the DA-IPC boutons in the proximal IPL were involved in "junctional appositions," that is, the junctions appeared to be specialized but they were different than classical chemical synapses. The synaptic organization of DA-IPCs in the goldfish IPL appears to be far more complex than previously thought. Although earlier studies have attempted to explain the action of dopamine in terms of interaction only with amacrine cells, the present study shows that effects involving bipolar cells, other DA-IPCs, unidentified processes and cell bodies in the GCL and OFL must be considered as well. PMID- 2908725 TI - The effects of serotonin agonists and antagonists on the response properties of complex ganglion cells in the rabbit's retina. AB - Selective agonists and antagonists were employed to determine the role of indoleaminergic amacrine cells in the generation of the light-evoked responses and spontaneous activity of direction and orientation selective cells. Perfusion with 5-HT2 antagonists reduced the spontaneous activity and both the leading and trailing edge responses of ON/OFF direction selective cells. 5-HT1a agonists had a similar effect on this class of cell, namely, a reduction of light-evoked and spontaneous activity. Results from ON-center and OFF-center orientation selective cells were consistent with those obtained from direction selective cells in that no disruption of direction or orientation selectivity was observed during perfusion of these drugs. These data suggest that the indoleaminergic cells are not directly involved in the generation of the trigger features of complex ganglion cells, but may be facilitating synaptic transmission in the inner retina. This function is discussed relative to the connectivity of the rod bipolar cells and the putative indoleaminergic amacrine cells. The similarity of the effects of 5-HT1a agonists and 5-HT2 antagonists supports the hypothesis, developed during our prior studies of brisk ganglion cells, that these two receptor classes mediate antagonistic processes in the target neurons. PMID- 2908727 TI - Anesthesia and paralysis in experimental animals: report of a workshop held in Bethesda, Maryland, October 27, 1984. Organized by the Visual Sciences B Study Section, Division of Research Grants, National Institutes of Health. PMID- 2908726 TI - Suppression of cone-driven responses by rods in the isolated frog retina. AB - The sensitivity of rod- and cone-driven responses was studied in the isolated frog retina during the period of rapid dark adaptation following a conditioning flash which bleached a negligible amount of visual pigment. Following a conditioning flash, cone-driven b-wave responses were first enhanced and then depressed. The time courses of the enhancement and subsequent depression of cone drive responses varies greatly with the intensity and wavelength of the conditioning flash, but were identical when the conditioning flashes were matched for equal excitation of 502 nm rods. These changes in cone-driven response sensitivity were correlated with the desensitization and recovery of rods following the conditioning flash. When signal transmission from rods to second order cells was interrupted by the addition of L-glutamate, the conditioning flash did not produce the above-described enhancement and subsequent depression of long-wavelength receptor potential responses. The suppression of cone-driven response therefore appears to be due to a synaptically mediated influence from 502 nm rods which is maximal when the rods are in the dark-adapted state, with little or no contribution from 433 nm rods, and no involvement of the pigment epithelium. PMID- 2908728 TI - Clinical significance of thyrotrophin binding inhibitor immunoglobulins in patients with Graves' disease and various types of thyroiditis. PMID- 2908729 TI - Possible correlation between non-insulin dependent diabetes mellitus (NIDDM) and restriction fragment length polymorphism (RFLP) of the 5'-flanking region of insulin gene in Korean diabetic population. PMID- 2908730 TI - [Neurochemistry of the mesencephalic substantia nigra: interrelations between excitatory amino acids, N-methyl-D-aspartate type receptors and intrinsic neuronal systems]. AB - Recent studies have demonstrated the existence of cortico-nigral fibers in the brain which may use L-glutamic or L-aspartic acid as their transmitters. Such cortico-nigral neuronal pathway seems to functionally interact with intrinsic neuronal systems in substantia nigra (SN) by first activating different subtypes of excitatory amino acid (EAA) receptors. Particularly interesting are results showing that activation of N-methyl-D-aspartate (NMDA) subtype receptor may evoke the Ca(2+)-dependent release of dopamine from dendrites of nigro-striatal neurons. In addition, NMDA and other EAA receptors may influence the functional activity of gabaergic, glycinergic and peptidergic neurons located in SN. Acidic aminoacid-containing neurons in SN may thus play a pivotal role in determining the outflow information from SN to caudal motor-related as well as rostral limbic related areas in the brain. PMID- 2908731 TI - [Pharmacology-biochemistry and physiopathology of tardive dyskinesia: review of the latest findings and controversies]. AB - Tardive dyskinesia is described as a distinct neurological entity. Its probable etiology, pathophysiology and biochemical pharmacology are reviewed and discussed in the light of the latest findings. PMID- 2908733 TI - Production of suppressor factors induced by ultraviolet irradiation or cis urocanic acid requires Lyt-2+ lymphocytes. AB - Both ultraviolet (UV) irradiation and cis-urocanic acid (UCA) are reported to be associated with the suppression of contact hypersensitivity (CHS) and the induction of a soluble factor which suppresses leukocyte adherence inhibition (LAI) assays in vitro. The cellular origin of the suppressor factor (SF) has now been investigated in vivo and in vitro, using monoclonal antibodies against lymphocyte surface markers to deplete certain cell populations, namely T lymphocytes bearing the L3T4 (helper) and Lyt-2 (suppressor) markers. Depletion of Lyt-2+ cells from irradiated mice in vivo and from spleen cell cultures in vitro led to the elimination of detectable levels of SF. Depletion of L3T4+ cells had no such effect. Similarly, Lyt-2+ cells (but not L3T4+ cells) were shown to be necessary for the production of SF by normal spleen cells cultured with cis UCA. These data suggest that the production of SF following UV irradiation may be related to the action of cis-UCA on Lyg-2+ lymphocytes. PMID- 2908734 TI - Improved separation of multi-locus hypervariable DNA restriction fragments by field inversion gel electrophoresis and fragment detection using a biotinylated probe. AB - DNA probes to multiple hypervariable human genomic loci are potentially highly informative as regards individual genome identification and parentage studies. However the resultant Southern blot patterns are generally highly complex and their interpretation difficult, with one important limitation being the extent of fragment separation and resolution. The separation of large DNA restriction fragments in agarose gels may be improved, in comparison to separations obtained by conventional electrophoresis, by the use of field inversion techniques. This is demonstrated by the analysis of the complex human Satellite III related DNA polymorphism. Detection of the Satellite III related restriction fragments is achieved either by using a [35S]-labelled probe (228S) or by using the same probe in a convenient non-isotopic form constructed by the photobiotin process. In addition, the probe 228S is useful for sexing the human genome, by the identification of a Y-specific restriction fragment. PMID- 2908735 TI - The effects of field inversion electrophoresis on small DNA fragment mobility and its relevance to DNA polymorphism research. AB - The electrophoretic mobility of several DNA size markers of molecular lengths from 1.23 x 10(2) to 2.36 x 10(4) base pairs has been investigated in gels of 1% and 1.3% agarose (w/v) by field inversion gel electrophoresis (FIGE), in vertical slabs. Pulsing times studied were in the range of 0.3/0.1 ms to 300/100 ms. (Pulsing times are given in milliseconds, as X/Y, where X is the forward pulsing time and Y is the reverse time.) FIGE differentially retards DNA migration: this effect is more marked for shorter pulsing times, and varies as a function of molecular length of the DNA fragment, down to fragments as small as about 1.7 kb, with the pulsing times we used. Several FIGE conditions were found which generate improved resolution of DNA fragments in different size ranges. DNA separation improves by more than a factor of two for fragments of 23.1-9.4 kb (with 300/100 ms pulsing) and for fragments of 4.4-2.0 kb (3/1 ms). FIGE does not seem to have a marked resolution enhancing effect on DNA sized from 9.4-4.4 kb. An example of improved detection of closely spaced bands on Southern blots is shown. PMID- 2908732 TI - Properties of labetalol, a combined alpha- and beta-blocking agent, relevant to the treatment of myocardial ischemia. AB - Labetalol, a combined alpha-beta-adrenergic antagonist, is one of the new group of beta-adrenergic blockers reduces peripheral and coronary vascular resistances while preserving cardiac output. Unlike alpha-adrenergic blockers, labetalol tends to reduce heart rate during rest and exercise. The drug is a potent antihypertensive agent which has been used by mouth and by vein to treat mild, moderate, and severe hypertension, including hypertensive emergencies. Labetalol has a hemodynamic profile which makes it an attractive agent for treating myocardial ischemia. The drug reduces blood pressure, left ventricular wall tension, heart rate, and contractility while preserving or even augmenting coronary blood flow. Studies with labetalol in hypertensive patients with angina have shown it to be more effective than placebo in reducing angina attacks and blood pressure while improving exercise tolerance. The drug appears to have antianginal and antihypertensive effects comparable to atenolol and propranolol. Side effects of treatment are observed and most are related to alpha- and beta adrenergic blockade. Labetalol also appears to be effective for treatment of normotensive patients with angina and for silent myocardial ischemia. It has no apparent effects on serum lipids and lipoproteins. Labetalol appears to be a useful drug for treating the hypertensive heart and its many complications. PMID- 2908736 TI - [Celiprolol]. PMID- 2908737 TI - Immunologic abnormalities in patients with chronic delta infection. AB - Data reported in this paper emphasize the existence of close relationships between hepatitis delta patients and subjects affected by other viral diseases, first of all AIDS and related conditions. Some immunologic abnormalities characterizing initial stages of HIV infection (reduced CD4/CD8 ratio, based on increased CD8+ cells; B-cell polyclonal activation with the presence of circulating immune complexes) were found, in fact, also in delta patients. No statistically significant difference was observed by comparing delta vs no delta subjects. PMID- 2908738 TI - [Prevalence and prognostic significance of anti-HTLV-I and anti-HIV-2 antibodies in patients with HIV infection in the Roman region]. AB - A chronic coinfection with CMV, EBV etc. has been described in patients with HIV infection; recently a coinfection with other retroviruses has been described too. We have looked for the presence of antibodies to HTLV-I (anti HTLV-I) and to HIV 2 (anti HIV-2) in 135 HIV infected (HIV-positive) subjects living in Rome. They were 100 i.v. drug addicts, 24 homo/bisexuals, 4 partners of HIV-positive patients, 5 polytransfused and 2 without any known risk factor; 32 of them had a full-blown AIDS, 52 had ARC and 51 were symptom-free. Anti HIV, anti HTLV-I and anti HIV-2 were detected with ELISA method and confirmed by Western Blot (W.B.) technique. Antibodies to HTLV-I were found in 14 cases (10.4%) and antibodies to HIV-2 in 12 cases (8.9%). The contemporary presence of anti HIV, anti HTLV-I and anti HIV-2 was not found in any subjects. Our data fail to show a clear relationship among the coinfection with different retroviruses and the various risk factors for HIV infection and the HIV-related clinical picture (AIDS, ARC, etc.). PMID- 2908739 TI - [Vertical transmission of immunity against B. pertussis]. AB - Carrying out serological exams either from the blood of the woman in labor or from the umbilical cord at the moment of the birth, the AA. evaluate the rate of specific anti-pertussis antibodies which are transferred from the mother to the foetus through the placenta. The discovered rates are not quantitatively such to represent a protection from the infection. Certainly, through the breast feeding the newborn receives a further contribution in specific antibodies, but it is also true that the two mechanisms do not always produce additive results. Further, it is to be considered that this kind of protection has only a limited duration. The AA, conclude by hoping that in the near future there will be more efficacious vaccines free from the risk of serious complications, that today can be estimated at values of 1:300.000. PMID- 2908740 TI - Electron microscopy and image analysis of the complexes I and V of the mitochondrial respiratory chain. AB - The results of Section IV can be summarized in a simple ATP synthase model. This model implies that either the alpha or the beta subunits must be closer to the membrane. The work of Gao and Bauerlein (1987) indicates that the alpha subunits are closer to the membrane. Although the overall structure is more or less clear, important questions need to be clarified. First, the number and the arrangement of the subunits in the F0 part must be known. Second, the exact shape of F1, and particularly the shape of the large subunits needs to be elucidated. On the basis of fluorescence resonance energy transfer measurements by McCarty and Hammes (1987), a model was presented showing large oblong subunits. Such 'banana-shaped' subunits, which are also presented in the many phantasy models (e.g. Walker et al., 1982), are very unlikely in view of the electron microscopical results, although the large subunits do not need to be exactly spherical. The third and most interesting central question is on the changes in the structure that take place during the different steps in the synthesis of ATP. It can now be taken as proven that the energy transmitted to the ATP synthase is used to induce a conformational change in the latter enzyme, in such a way as to bring about the energy-requiring dissociation of already synthesized ATP (Penefsky, 1985 and reviewed in Slater, 1987). But the way in which the three parts of the ATP synthase are involved is completely unknown. It is rather puzzling that such a long distance exists between the catalytic sites, which are on the interface of the alpha and beta subunits and the F0 part where the proton movements occur, which, according to Mitchell's theory (1961), is the driving force for the synthesis of ATP. Perhaps alternative mechanisms such as the collision hypothesis formulated by Herweijer et al. (1985) are more realistic in describing the mechanism of ATP synthesis. It would bring the complexes I and V close together, not only in the artificial way treated in this paper, but in a useful way for energy conversion. PMID- 2908741 TI - 44th All-India Ophthalmological Conference. Proceedings of the Kanpur Conference- 1986. PMID- 2908742 TI - International meeting on the association between rheumatoid arthritis and mycobacterial infection. PMID- 2908743 TI - Evidence that Thy-1 and Ly-5 (T-200) antigens interact with sulphated carbohydrates. AB - Recent studies have demonstrated that lymphocytes express an array of cell surface receptors for sulphated polysaccharides (SP). Experiments were undertaken to determine the binding characteristics of these receptors and establish whether any known lymphocyte cell surface antigens interact with sulphated carbohydrates. It was found that murine thymocytes lack receptors for chondroitin-4-sulphate but express saturable, high affinity binding sites for heparin, fucoidan and dextran sulphate, with an apparent affinity constant range of 0.03-2.6 x 10(-9) mol/l. Binding inhibition experiments revealed one class of binding sites on murine thymocytes that is shared by heparin, fucoidan and dextran sulphate and another class of sites that is dextran sulphate-specific. The cell surface receptors for the SP were affinity-purified by applying detergent lysates of 125I-labelled thymocyte membranes to SP-coupled solid supports. It was found that the Thy-1 and Ly-5 (T-200 or leucocyte common antigen) molecules of murine thymocytes bind to sulphated carbohydrates, although the two molecules differed substantially in their reactivity with the four different SP tested. Furthermore, only subpopulations of the Thy-1 and Ly-5 molecules interacted with sulphated sugars. Four additional sulphated carbohydrate-binding molecules were also detected. It is suggested that the SP-binding molecules are involved in the interaction of lymphocytes with glycosaminoglycans on other cells and in the interstitial space. PMID- 2908744 TI - The effect of internal mammary artery grafting on the perioperative course. AB - Internal mammary artery (IMA) grafts are being used for myocardial revascularization with increasing frequency because of a higher 10-year patency rate and actuarial survival rate as compared to saphenous vein grafts. This study sought to evaluate whether IMA grafts are associated with an increased usage of blood and blood products, operating time, postoperative hospital stay, or incidence of reoperation due to bleeding. A total of 189 consecutive patients undergoing aortocoronary bypass procedures (group I, N = 59, with no IMA grafts; group II, N = 108, with single IMAs; and group III, N = 22, with double IMAs) were studied over 6 months. Significant differences were seen in their age (group I, 71.6 years; group II, 62.1 years; and group III, 57.1 years); cross-clamp time (62 minutes for group I, 65 minutes for group II, and 83.7 minutes for group III); and duration of operation (400 minutes for group I, 423 minutes for group II, and 501 minutes for group III). Use of blood products including packed red blood cells, fresh frozen plasma, and platelets during the operation and postoperatively was similar in all three groups. The duration of postoperative hospital stay was statistically similar for each group, being 16.6 days for group I, 13.1 days for group II, and 13.7 days for group III. The number of vessels grafted was statistically similar for groups I and II (3.1 and 3.3 vessels, respectively), but group III had a statistically larger number of vessels grafted (3.7 vessels). The reoperation rate for bleeding was similar for all three groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2908745 TI - [AIDS and human lymphocytes]. AB - HIV infection is no doubt the primary cause of AIDS. But the relationship between HIV and its host lymphocytes is fairly complicated. It has become clear that the host range of the viruses varies according to the clinical stage of the patients from whom viruses were isolated. Besides, the cause or mechanism of cell killing by HIV infection is not well-known. The density of CD4 molecules on the cell surface can not simply explain the phenomena, such as the level of virus growth, killing mechanisms of lymphocytes and host range of the virus. It is quite interesting to analyse which gene of the virus determines the characteristics of the virus. PMID- 2908746 TI - Review article: beta-adrenoceptor blockers for the treatment of portal hypertension. AB - beta-Adrenoceptor blockers always change splanchnic haemodynamics in cirrhotic patients. Azygous blood flow, as a measure of collateral circulation including that through varices, is always reduced, but the effects on portal pressure, whether measured directly or by the wedged hepatic venous pressure, are variable. The initial correlations between a 25% reduction of resting pulse rate and similar percentage reduction in the wedge-free hepatic venous gradient, has not been reproduced in subsequent studies. Therefore, to study the effect of changes in haemodynamic indices and the likelihood of variceal bleeding, direct measurements of such indices need to be made in clinical trials. At present there are no haemodynamic or clinical factors which can be used to select patients who will have a good therapeutic response to propranolol other than those documented in the first clinical trial of propranolol for the prevention of variceal re bleeding from Paris. Thus the hypothesis that beta-adrenoceptor blockers may lessen the incidence of bleeding in cirrhotics, by partially reducing portal pressure or flow or both, needs testing in further clinical studies. The selection criteria of the first clinical trial of propranolol in Paris need to be confirmed. Two subsequent trials, in which patients were not selected but in which many patients had similar clinical characteristics to the Paris patients, could not confirm a therapeutic effect of propranolol. No fatal complications due to propranolol administration have been reported in cirrhotic patients. Complications are reversible. Pharmacological treatment including beta adrenoceptor blockade appears ideal for trials of primary prevention of variceal bleeding. Some preliminary results including use in decompensated cirrhotics are encouraging. However, as for trials for prevention of re-bleeding, the design and analysis of such trials needs careful evaluation to take into account the outcome of patients who discontinue medication, whether due to simple noncompliance or due to side-effects, and also the influence of abstinence from alcohol on bleeding from varices. PMID- 2908747 TI - Omeprazole in peptic ulcers resistant to histamine H2-receptor antagonists. AB - Eighteen patients with duodenal, gastric or jejunal ulcers, resistant to at least 3 months treatment with histamine H2-receptor antagonists, singly or in combination with other anti-ulcer drugs, were treated with 40 mg omeprazole once daily for up to 8 weeks. All ulcers healed, the majority within two weeks. After ulcer healing patients were given maintenance therapy with high doses of cimetidine or ranitidine. Of 15 patients on maintenance therapy with H2-receptor antagonists, 12 (80%) developed a relapse after a period ranging from 3 to 52 weeks. Two patients were lost to follow-up. After re-healing on 40 mg omeprazole, two patients were given 20 mg omeprazole daily as maintenance therapy but relapses occurred again after 14 and 26 weeks respectively. After re-healing on 40 mg omeprazole, these two patients and one additional patient received maintenance therapy with 40 mg omeprazole daily. At present these three patients have been relapse-free for periods varying from 16 to 52 weeks. No side effects were registered during treatment with omeprazole. It is therefore concluded that omeprazole is highly effective in healing refractory peptic ulcers and that omeprazole maintenance therapy may be useful for prevention of relapse. Patients are sometimes seen with peptic ulceration which appears resistant to therapy with histamine H2-receptor antagonists, colloidal bismuth subcitrate, sucralfate or pirenzepine, either given as monotherapy for a prolonged period of time or as combination therapy. Usually the reason for such therapeutic failure remains obscure. Whether virtually total abolition of acid secretion will allow ulcer healing in these circumstances is unknown.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2908748 TI - The gastric proton pump, a target for neuroleptics and antidepressant drugs? AB - The antisecretory action of the antidepressant drugs trimipramine, doxepin and nortriptyline was studied in two different in-vitro test systems; the isolated and enriched guinea-pig parietal cell and the purified H+/K(+)-ATPase preparation. The effect of the antidepressants was compared with that of the neuroleptic agents chlorpromazine, triflupromazine, trifluperazine, haloperidol, fluspirilene and with that of the tricyclic anticholinergic agent pirenzepine. All neuroleptics and antidepressants inhibited acid formation in intact parietal cells with IC50 values in the nanomolar range. The inhibitory potency for each compound was identical regardless of whether histamine or db-cAMP was used as stimulant. Isolated H+/K(+)-ATPase, measured in the presence of 5 mmol litre-1 KCl, was inhibited by all psychotropic drugs with IC50 values in the micromolar range. EGTA did not affect the inhibitory potency at the H+/K(+)-ATPase, indicating that the action of the drugs does not depend on their calmodulin blocking activity. Pirenzepine was ineffective in both test systems. Kinetic studies done with nortriptyline, chlorpromazine and haloperidol showed a competitive type of inhibition with respect to K+ at low inhibitor concentrations. This competitive type was changed to a mixed type of inhibition with increasing inhibitor concentrations, demonstrating cooperative effects between drug binding and K+ activation of the enzyme. From these data it is suggested that antidepressants and neuroleptics act by an allosteric mechanism of action, and that the lipid solubility is a significant factor to establish enzyme inhibition. PMID- 2908749 TI - Review: long-acting somatostatin analogues. AB - This article reviews the chemistry, actions and chemical applications of somatostatin and its analogues. At present, their gastroenterological use should be considered in patients with the carcinoid syndrome and functioning pancreatic endocrine tumours; in endocrinology there is interest in their use for the management of patients with resistant acromegaly. With these possible exceptions, somatostatin analogues should at present be used only in the context of clinical trials. PMID- 2908750 TI - Adverse reactions to sulphasalazine and 5-amino salicylic acid in the same patient. AB - We report a patient who developed sulphasalazine-related hepatitis with a subsequent adverse reaction to rectal 5-amino salicylic acid, in the form of pain and fever without associated liver dysfunction, suggesting reactions to both components of sulphasalazine. Included is a review of the literature. Caution should be observed when prescribing 5-amino salicylic acid to sulphasalazine intolerant patients. PMID- 2908751 TI - The effects of roxatidine acetate (HOE-760) on 24-hour intragastric acidity in healthy volunteers: comparison with ranitidine and placebo. AB - In a series of double-blind randomized studies in normal volunteers using continuous intragastric pH monitoring, the effects of different dosage regimens of roxatidine, a new H2-receptor antagonist, were compared with placebo and ranitidine. Roxatidine acetate, 75 mg twice daily, decreased median 24 h gastric acidity from pH 1.6 to 3.2 and median nocturnal acidity from 1.5 to 3.0. Roxatidine acetate, 150 mg at bedtime, raised median 24 pH of the same 17 subjects to 2.4 and nocturnal pH to 5.9. In another series of experiments, 150 mg roxatidine acetate at bedtime was as effective as ranitidine 300 mg nocte raising median nocturnal pH (14 volunteers) from 1.4 to 6.65 compared to 6.7, respectively. However, when drugs were taken after the evening meal (post cenam nocte, pcn) roxatidine acetate 150 mg was less potent than ranitidine 300 mg with median night-time pH rising from 1.3 to 3.2 and 4.0, respectively, in 28 volunteers. Roxatidine acetate 300 mg pcn raised the pH to 4.9 suggesting that roxatidine is 1-2 times as potent as ranitidine, on a milligram-for-milligram basis. PMID- 2908752 TI - Somatostatin compared with cimetidine in the treatment of bleeding peptic ulcer without visible vessel. AB - In a randomized double-blind trial 100 patients with severe bleeding peptic ulcers were treated with an intravenous (i.v.) infusion of cimetidine or somatostatin. Only those patients in whom endoscopy performed within 6 h of admission showed non-arterial bleeding or signs of recent haemorrhage without a visible vessel entered the trial. The two treatment groups were well matched for age, sex, presence of underlying disease, prior ingestion of ulcerogenic drugs, tobacco habits, type of bleeding, haematocrit at admission, presence of hypovolaemic shock, source of bleeding and endoscopic findings. Four patients in each group were excluded after randomization. Further haemorrhage occurred in eight (17.3%) patients in the somatostatin group and in 10 (21.7%) in the cimetidine group, but the difference was not statistically significant. The number of surgical procedures, blood transfusion requirement, duration of hospitalization and mortality rates were similar in the two treatment groups. These results suggest that somatostatin does not improve the results obtained with cimetidine in patients with bleeding peptic ulcer, in whom the endoscopy discloses non-arterial bleeding or signs of recent haemorrhage without a visible vessel. PMID- 2908753 TI - Review: interactions between H2-antagonists and non-steroidal anti-inflammatory drugs. AB - Non-steroidal anti-inflammatory drugs (NSAIDs) are being prescribed increasingly with an H2-antagonist. This article reviews those published studies which have examined the potential for pharmacokinetic and, where appropriate, pharmacodynamic interactions between these classes of drugs. Studies involving the administration of a single dose of a NSAID to young healthy volunteers are of limited relevance in establishing the likely effect of an H2-antagonist on the blood concentrations of an NSAID in patients. Appropriate studies are those which will examine the effects of H2-antagonists on the steady-state pharmacokinetics of NSAIDs in patients with inflammatory joint diseases. More of such studies are required, particularly involving elderly patients. PMID- 2908754 TI - Inhibition of intestinal macrophage chemotaxis to leukotriene B4 by sulphasalazine, olsalazine, and 5-aminosalicylic acid. AB - Purified intestinal macrophages obtained at resections for colonic neoplasms were investigated for chemotaxis to leukotriene B4 (LTB4) by the Millipore filter assay and leading front technique. Possible inhibition by drugs effective in the treatment of chronic inflammatory bowel disease (sulphasalazine, olsalazine, its active moiety 5-aminosalicylic acid (5-ASA), and the 5-ASA metabolite N acetylated-5-ASA (ac-5-ASA)) was tested at therapeutic colonic concentrations of 0.01-10 mM. Leukotriene B4 at a dose of 10 nM was equipotent with casein (5 g litre-1) as regards chemoattraction of macrophages. Sulphasalazine, olsalazine and 5-ASA were potent inhibitors of macrophages chemotaxis to LTB4 with IC50 values of 0.43, 0.39 and 0.24 mM, respectively. These concentrations are below the lowest concentration of 5-ASA (2 mM) in the colonic lumen during conventional sulphasalazine treatment of patients with chronic inflammatory bowel disease. The inhibition of macrophage chemotaxis by these drugs may be important for this limitation of the local inflammatory process in chronic inflammatory bowel disease, and may in part explain the beneficial effect of systemic and local treatment with sulphasalazine. Leukotriene B4 appears to be an important inflammatory mediator for the activation of macrophages in colonic inflammation. PMID- 2908756 TI - The cost-effectiveness of maintenance therapy for duodenal ulceration with an H2 antagonist. AB - Data from several sources are used to quantify the expected direct medical costs of a recently healed duodenal ulcer patient prescribed an H2-antagonist (famotidine) for a 6-month period. These costs are compared to the expected direct medical costs associated with not using maintenance therapy. Our results indicate that the estimated direct cost of patients prescribed a 6-month regimen of an H2-antagonist (famotidine) is 30.3% lower than patients who receive no H2 antagonist therapy. Most of the savings result from a reduced risk of hospitalization and surgery. The results of the sensitivity analysis of four varying scenarios indicate that H2-antagonist maintenance therapy remains less costly even when the assumptions underlying the model are varied enormously. We conclude that the decision to withhold maintenance therapy with H2-antagonists should not be based on economics. PMID- 2908755 TI - Balsalazide in the maintenance treatment of patients with ulcerative colitis, a double-blind comparison with sulphasalazine. AB - Balsalazide (BSZ) is a pro-drug which releases 5-aminosalicylic acid (5ASA) and 4 aminobenzoyl-beta-alanine (an inert carrier) in the colon of various species including man. BSZ was compared with sulphasalazine (SASP) (both 1 g b.d. orally) in the maintenance of remission in patients with ulcerative colitis (UC). Seventy nine patients (53 male, 26 female), mean age 49 years (range 19-79 years), with UC were randomly allocated to either treatment (41 BSZ, 38 SASP) for 6 months. The groups were similar in respect of age, sex, duration and extent of disease. Seven patients defaulted (3 BSZ, 4 SASP) leaving 38 on BSZ and 34 on SASP. Two male patients, both receiving SASP, were withdrawn because of severe side effects. One of these patients, with an exfoliative rash, was maintained satisfactorily on open BSZ. Remission rates at 6 months (51% BSZ, 63% SASP) were not significantly different (life-table analysis P less than 0.1). Twelve patients (15%) reported troublesome side-effects (2 BSZ 5%, 10 SASP 26%, P = 0.017 Fisher Exact Test). Mean haemoglobin concentrations, similar on entry, increased after 6 months with BSZ (0.2 g/dl) but decreased with SASP (0.5 g/dl) (P less than 0.0002). BSZ was not significantly different from SASP in maintaining remission in patients with UC but had fewer side-effects. PMID- 2908757 TI - Double-blind study of an alpha 2 agonist in the treatment of irritable bowel syndrome. AB - A double-blind crossover trial of the alpha 2 agonist lidamidine hydrochloride in 72 patients with irritable bowel syndrome is reported. Lidamidine was found to have no significant effect on frequency and severity of abdominal pain or abdominal bloating. It did cause a statistically significant reduction in frequency of defaecation (P = 0.005), but this was of a degree unlikely to be of clinical importance. Although alpha 2 agonists inhibit gastrointestinal motility in animals this study suggests that lidamidine hydrochloride does not have a useful therapeutic role in irritable bowel syndrome. PMID- 2908758 TI - The role of H2-receptor antagonists in the prevention of NSAID-induced gastrointestinal damage. AB - Non-steroidal anti-inflammatory drugs (NSAIDs) induce gastric and duodenal damage in animals and humans. The possible protection afforded by cimetidine against acute and short-term NSAID-induced mucosal damage was evaluated in five studies. Cimetidine 200 mg once daily and 400 mg once daily was found to protect the gastric mucosa against damage induced by a single dose of aspirin 1300 mg; this protection was found to be independent of gastric acid secretion. Cimetidine 200 mg q.d.s. was found to protect the stomach and duodenum against damage induced by 14 days' treatment with aspirin 650 mg q.d.s. Duodenal and gastric damage induced during a 7-day treatment period with naproxen 500 mg b.d. was prevented by cimetidine 400 mg b.d.; this dose of cimetidine also provided significant duodenal protection against damage induced by 1 week of therapy with indomethacin 50 mg t.d.s. There is no correlation between upper gastrointestinal symptoms, or between mucosal prostanoids, and the presence or absence of mucosal damage. Cimetidine is therefore effective in the prevention of mucosal damage induced by short-term treatment with NSAIDs. PMID- 2908759 TI - Sudden cardiac deaths among psychiatric patients receiving neuroleptics. PMID- 2908760 TI - The mosquitoes of Sardinia: species records 35 years after the malaria eradication campaign. AB - 1. Thirty-five years ago malaria was eradicated from Sardinia by massive application of DDT directed against the mosquito vector species, Anopheles labranchiae, but the long-term effects on the mosquito fauna have not been investigated previously. 2. A 5-year mosquito survey (1980-85) involved in the inspection of 348 sites (plus 173 reinspections) and the processing of nearly 60,000 specimens. 3. Twenty-four species in six genera were identified from larval and adult collections. Species of the genera Culex (41%) and Aedes (22%) were more commonly encountered than Culiseta (18%) and Anopheles (17%) species. Orthopodomyia (1.6%) and Coquillettidia (0.6%) were far less frequent. 4. The species composition was similar to that described for the years of the eradication campaign, except for the genus Anopheles. Of the eight Anopheles species previously recorded, only four species were identified in collections of 1159 larvae from eighty-five positive sites. 5. Anopheles labranchiae was the most frequently collected species of its genus (49%), but was represented in only 12% of the total collections. Comparison with previous records indicated a progressive increase in sites positive for An.labranchiae over the past 35 years. 6. Anopheles hispaniola was not found, although it had apparently replaced An.labranchiae soon after the eradication campaign. An. labranchiae was common in the sites where the replacement phenomenon has been observed. PMID- 2908761 TI - Studies of house-entering habits of mosquitoes in The Gambia, West Africa: experiments with prefabricated huts with varied wall apertures. AB - The house-entering behaviour of nocturnal mosquitoes was studied in The Gambia. Mosquitoes were captured as they attacked man in the open and in experimental huts which comprised 1.8 m cube frames with corrugated iron roofs and plywood walls of various heights. Catches of all species were similar in the open and in a roofed, but unwalled, hut frame. The mosquitoes taken in catches in unwalled huts and others with wall heights of 0.6, 1.2 and 1.7 m (giving an 8 cm eaves level entry slit) fell into two categories. The first group, which included the endophilic species Anopheles gambiae Giles s.l., An. melas Theobald and Mansonia spp. were only slightly affected by increasing wall height, but the second group, including the exophilic mosquitoes Aedes spp., An. pharoensis Theobald, Cx poicilipes (Theobald) and Cx thalassius Theobald showed a very marked progressive exclusion. In comparisons of catches in two huts with 8 cm entry slits at eaves or ground level, large numbers of An. pharoensis found access through the ground level entry but not at eaves level. No consistent difference could be demonstrated for other species. It is concluded that the house-entering behaviour which distinguishes endophagic mosquito species includes at least two distinct responses: flight upwards to eaves level and the passage from outside to indoors. It is also suggested that house entry as a component in host-seeking behaviour and indoor resting are distinct, but not necessarily exclusive, behavioural traits. PMID- 2908762 TI - The relative efficacy of repellents against mosquito vectors of disease. AB - Laboratory tests of insect repellents by various different methods showed that An.stephensi Liston was consistently more susceptible than An.gambiae Giles, An.albimanus Wiedemann or An.pulcherrimus Theobald. The six repellents tested were di-ethyl toluamide (deet), di-methyl phthalate (DMP), ethyl-hexanediol, permethrin, citronella and cedarwood oil. Testing systems in which the mosquitoes were presented with a choice gave consistently lower ED50 values than when there was no choice, i.e. the standards of tolerance are not absolute but depend on the options available. In field tests in an experimental hut a curtain with a high dose of di-ethyl toluamide (deet) reduced biting in the hut but had to be re impregnated frequently. Deet-impregnated anklets gave about 84% protection against Culex quinquefasciatus Say for 80 days after one impregnation, in a trial in which the anklets were brought out of sealed storage and tested for 2 h nightly. Similar protection was found against An.funestus Giles but the protection against An.gambiae s.l., An. coustani Laveran and Mansonia spp. was not as good. There were highly significant differences between the four collectors' mosquito attractiveness but this varied highly significantly between the mosquito species. PMID- 2908763 TI - Antibodies that block stimulation by TSH or TSAb of thyroid hormone secretion in primary hypothyroidism. AB - Antibodies that inhibit the stimulation of the thyroid by TSH have been studied in 63 patients with primary hypothyroidism of whom 34 had thyroid atrophy and 29 goitrous Hashimoto's thyroiditis. The method used measured the secretion of tri iodothyronine (T3) from porcine thyroid slices incubated in vitro. The aims of the study were to assess the frequency and clinical correlates of blocking antibodies in an unselected series of patients, to establish their IgG nature and to examine their action in relation to the TSH receptor. Blocking antibodies were found in 25% of patients and occurred in association with both atrophic (32%) and goitrous (17%) hypothyroidism. These antibodies did not bind TSH (with one exception) nor did they inhibit binding of TSH to its receptor (also with one exception). Blocking-antibody activity was abolished by treatment of the serum with anti-hIgG or with protein A, and the activity was purified from serum by affinity chromatography on protein A sepharose-4B, thus establishing the IgG nature of the antibodies. The stimulation of T3 secretion by thyroid-stimulating antibodies was also blocked and in one case, where IgG did not block stimulation by bTSH, stimulation by hTSH was blocked. Antibodies blocking the action of TSH probably represent an important mechanism in the pathogenesis of primary hypothyroidism in some patients. PMID- 2908764 TI - Effect of naloxone, domperidone and idazoxan on the delay in gastric emptying induced by ileal lipid. AB - Studies were carried out on 22 healthy male volunteers to investigate whether intravenous administration of either the opiate antagonist, naloxone, or the dopamine antagonist, domperidone, or the alpha 2-adrenoreceptor antagonist, idazoxan, could reverse the delay in gastric emptying induced by ileal infusion of lipid emulsion. Ileal infusion of 50% lipid emulsion significantly delayed the rate of gastric emptying compared with ileal infusion of isotonic saline (P less than 0.01). Intravenous infusion of naloxone (20 micrograms kg-1 hour-1) or prior administration of either intravenous domperidone (20 mg) or idazoxan (0.2 mg kg 1) did not inhibit the delay in gastric emptying induced by ileal infusion of lipid emulsion. These observations indicate that feedback regulation of gastric emptying by ileal lipid does not appear to be mediated by either dopaminergic or enkephalinergic neurons, nor by alpha 2-adrenoreceptors. PMID- 2908765 TI - The effect of two alpha 2-adrenoreceptor agonists and an antagonist on gastric emptying and mouth to caecum transit time in humans. AB - Experiments were performed to investigate the effect of two alpha 2 adrenoreceptor agonists, clonidine and lidamidine, and a specific alpha 2 adrenoreceptor antagonist, idazoxan, on gastric emptying and mouth to caecum transit time (MCTT) of a radiolabelled meal in 27 healthy male subjects. Lidamidine (20 mg p.o.) and clonidine (0.3 mg p.o.), given alone had no significant effect on gastric emptying or MCTT suggesting that the anti diarrhoeal action of clonidine and lidamidine are unlikely to be explained by a slowing of small intestinal transit. Idazoxan (20 mg p.o.) reversed the effect of clonidine in 10 subjects, who showed a delay in MCTT after taking clonidine, but did not alter MCTT under basal conditions. These results suggest that although the sympathetic nervous system can influence upper gastrointestinal motility by an action on alpha 2-adrenoreceptors, this action does not exert a tonic influence on upper gastrointestinal motility under basal conditions. PMID- 2908766 TI - The impact of H2-receptor antagonists on the complications, morbidity and mortality of peptic ulcer disease. AB - The epidemiology and character of peptic ulcer has changed over the last 20 years, with only some of the change being due to the introduction of H2-receptor antagonists in the mid-1970s. There is evidence that duodenal ulcer was declining before this change in therapeutics. H2-receptor antagonists have, however, greatly reduced the morbidity and the time off work due to peptic ulcer disease. There is no strong evidence, however, that mortality due to peptic ulcer disease, which was already relatively small, has been reduced. The incidence of complications such as gastric haemorrhage, perforation and obstruction, may have increased in elderly patients. This may be associated with independent variables, such as increased use of non-steroidal anti-inflammatory drugs. PMID- 2908767 TI - What are the differences between the H2-receptor antagonists? AB - The H2-receptor antagonists which are used for ulcer therapy fall into four main structural classes. Cimetidine is an imidazole derivative; ranitidine belongs to the basically substituted furans, famotidine is a member of the guanidinothiazole group; and roxatidine belongs to the aminoalkylphenoxy series. Famotidine is the most potent, selective H2-receptor antagonist yet available for ulcer therapy. On a weight basis, famotidine is approximately eight times more potent than ranitidine and 40 times more potent than cimetidine. Cimetidine, ranitidine and famotidine are competitive antagonists, while the long-acting H2-receptor antagonists, e.g. loxtidine and lamitidine, are insurmountable H2-receptor blockers. Famotidine has a longer duration of action than either ranitidine or cimetidine. Because famotidine does not interact with cytochrome P-450 of the hepatic enzyme system, it does not appear to affect the metabolism of drugs metabolized by this system. The overall number of side-effects of the H2-receptor antagonists is in the range of 2-3% and no irreversible adverse effects are known. Famotidine has been found to be generally well tolerated. In a first post marketing study, the number of patients with side-effects was only 0.43%. Side effects such as headache, dizziness, constipation and diarrhoea have been observed only occasionally. Thus, famotidine is a safe and potent H2-receptor blocker of acid secretion. PMID- 2908768 TI - Developmental regulation of nodule-specific genes in alfalfa root nodules. AB - We have cloned alfalfa nodule-specific cDNAs that code for leghemoglobin (Lb), glutamine synthetase (GS), and three unidentified nodulins. Hybrid-select translation of nodule RNA followed by 2-D gel electrophoresis showed that the Lb specific cDNA corresponded to at least four Lb species of 12 kDa. One of the unidentified cDNA clones (N-32/34) corresponded to at least five polypeptides of 32-34 kDa; a second unidentified cDNA clone (N-14) corresponded to an individual polypeptide of 14 kDa. The in vitro translation product(s) of the RNA hybrid selected by the third unidentified cDNA clone (N-22) formed a single band at 22 kDa on a one-dimensional gel. Northern and dot blot analyses of RNA isolated from wild-type nodules and from defective nodules elicited by a variety of Rhizobium meliloti mutants showed that 1) RNAs corresponding to the Lb, nodule-specific GS, and three unidentified nodulins were coordinately expressed during the course of nodule development, and 2) all five nodulins were expressed in Fix- nodules that contained infection threads and bacteroids but were not expressed in nodules that lacked infection threads and intracellular rhizobia. PMID- 2908769 TI - In vivo and in vitro metabolism of 3,4-(methylenedioxy)methamphetamine in the rat: identification of metabolites using an ion trap detector. AB - Four biotransformation pathways of 3,4-(methylenedioxy)methamphetamine (MDMA) in the rat have been identified: N-demethylation, O-dealkylation, deamination, and conjugation (O-methylation, O-glucuronidation, and/or O-sulfation). The specific MDMA metabolites that have been identified are 3-hydroxy-4 methoxymethamphetamine, 4-hydroxy-3-methoxymethamphetamine, 3,4 dihydroxymethamphetamine, 4-hydroxy-3-methoxyamphetamine, 3,4 (methylenedioxy)amphetamine (MDA), (4-hydroxy-3-methoxyphenyl)acetone, [3,4 (methylenedioxy)phenyl]acetone, and (3,4-dihydroxyphenyl)acetone. All except 3,4 dihydroxymethamphetamine were present in the urine. The hydroxylated metabolites were excreted in the urine as the O-glucuronide and/or O-sulfate conjugates, but traces of free 4-hydroxy-3-methoxymethamphetamine and 4-hydroxy-3 methoxyamphetamine were also present in unhydrolyzed urine. N-Demethyl and 3-O methyl phenolic amine metabolites of MDMA were consistently present in brain, liver, blood, and feces. MDMA was metabolized by the 10000g rat liver supernatant to 4-hydroxy-3-methoxymethamphetamine, 3,4-dihydroxymethamphetamine, MDA, and [3,4-(methylenedioxy)phenyl]acetone. Also, the 10000g rat brain supernatant metabolized MDMA to 4-hydroxy-3-methoxymethamphetamine, 3,4 dihydroxymethamphetamine, 4-hydroxy-3-methoxyamphetamine, and MDA. PMID- 2908770 TI - Effects of aminothiols in 2-acetylaminofluorene-treated rats. I. Damage and repair of liver DNA, hyperplastic foci, and Zymbal gland tumors. AB - One hundred and seventy-nine male Wistar rats were divided into 6 groups and fed with a standard diet supplemented with 0.05% 2-acetylaminofluorene (2AAF) and/or 0.1% glutathione (GSH) or N-acetyl-L-cysteine (NAC). Each treatment cycle lasted for 3 weeks, followed by 1 week of standard meal. After 4 cycles, survival was 100% in the 3 control groups, and 86.0, 100 and 91.7%, in the groups receiving 2AAF, 2AAF plus GSH, and 2AAF plus NAC, respectively. After an additional 4-8 weeks, all the 5 surviving rats fed with 2AAF exhibited deforming ear tumors, which on histological examination were classified as sebaceous squamocellular carcinomas of Zymbal glands. No such tumors were detectable in control groups, nor in the 16 surviving rats fed with 2AAF plus GSH or NAC. In the liver, 2AAF produced significant DNA damage at the 3rd week of each cycle, which was partially repaired during the week of standard meal feeding. Moreover, 2AAF determined the appearance of gamma-glutamyl transpeptidase-positive foci, which tended to increase with time both in number and in size. GSH and NAC exerted similar protective effects on these phenomena, but only at early stages of the experimental model used. PMID- 2908771 TI - Viruses in the pathogenesis of systemic lupus erythematosus. AB - In spite of the lack of firm evidence implicating infectious agents, it is still likely that SLE requires an initiating event, probably environmental, and possibly infectious. In the setting of genetically determined perturbations of the immune system, an infectious trigger could be a trivial event clinically, and could be different in different patients. Once triggered, the immunologic abnormalities might be self-perpetuating so that the persistent infection and foreign antigens as found in hepatitis B vasculitis, might not be needed in SLE. Current evidence has not firmly implicated any specific microbial agents, but on a theoretical basis, the human retroviruses are particularly attractive candidates. PMID- 2908773 TI - Pattern formation: from theoretical models to molecular biology. AB - The field of pattern formation in biological systems is viewed, taking into consideration the major theoretical and experimental information. The basic idea which has emerged from the different theoretical models is that short range cell to-cell interactions could manifest the hierarchy of patterns. These interactions could actually be governed by simple signals in the cell surface. In the second part the experimental evidence is examined, namely, the genes that control pattern formation in Drosophila. The products of these genes display a variety of characteristics ranging from being molecules at the cell surface to regulatory proteins in the nucleus. The hypothesis is presented that molecules in the cytoplasm could connect the two parts. According to this, signals at the cell surface and subsequent cell-to-cell interactions should be of primary importance in the mechanisms that underlie morphogenesis. PMID- 2908772 TI - Counteraction by combined treatment with high dose of oestrogen and somatostatin of mammary growth suppression in mice. AB - The interaction between somatostatin (SMS) and high doses of oestrogen on mammary gland growth was examined in C3H/He virgin mice. Mammary gland growth was significantly suppressed by the subcutaneous implantation of pellets of oestradiol benzoate diluted to 1/1000 or 1/500 or by injection twice daily of 50ng SMS 201-995 between 25 and 55 days of age. However, the mammary gland growth of mice receiving SMS and oestrogen in combination was markedly stimulated compared to that of mice given the respective agents. These results indicate that the inhibitory effects of somatostatin and oestrogen on mammary growth were apparently counteracted by the treatment in combination. PMID- 2908774 TI - Clinical, morphopathological and toxicological studies in acute benzodiazepine poisonings. PMID- 2908775 TI - Use of the in situ and free internal thoracic artery for myocardial revascularization. PMID- 2908776 TI - Mosquito larvae survey in Ain-Ghosin village, Ismailia Governorate. PMID- 2908777 TI - IVth International Symposium on Cardiac Bioprostheses, April 14-17, 1988, Del Coronado, California. PMID- 2908779 TI - IVth International Symposium on Cardiac Bioprostheses, April 14-17, 1988, Del Coronado, California. PMID- 2908778 TI - IVth International Symposium on Cardiac Bioprostheses. PMID- 2908780 TI - Paternity testing: current status and review. PMID- 2908781 TI - Immune mechanisms in transfusion. PMID- 2908782 TI - Breeding-site productivity of the swamp forest mosquitoes Mansonia bonneae and Ma. dives in Sarawak, east Malaysia. AB - Studies on larval population densities and adult emergence rates of the Brugian filariasis vectors Mansonia bonneae Edwards and Ma. dives Schiner were conducted in freshwater swamp forest bordering the Sadong River, Serian District, Sarawak, East Malaysia, during 1984-85. Three species of aquatic host-plants in the Family Araceae were identified as supporting immature stages of the Ma. bonneae/dives complex. Proportions of positive plants were 4.7%, 6.5% and 3.4% with 6.4 +/- 2.6, 7.3 +/- 2.8 and 10.1 +/- 1.1 larvae per positive plant, respectively, for the plant species Homalomena cordata Schott, H. rostrata Griffiths and Hydrostemma motleyi (Hook. f.) Mabberley. These data indicate no significant preferences between the three types of host-plant. Detailed monitoring of the host-plant H. cordata revealed no significant monthly fluctuations in larval density per plant nor the proportion of positive plants. 11.6% of larvae were Ma. dives and 88.4% were Ma. bonneae. Mean daily yields of Ma. bonneae/dives adults per square metre of H. cordata vegetated water surface were 0.45 males plus 0.57 females during the wet season (December-February) compared with 0.2 males plus 0.31 females during the dry season (June-August). Thus output of adults per plant was approximately halved, and suitable breeding areas were further reduced, during the dry season. By extrapolation from these rates, a crude mean estimate for productivity of Ma. bonneae/dives females is 1.6 million per hectare per annum in swamp forest habitats vegetated with any of the host-plants studied. PMID- 2908783 TI - Diel activity patterns of blood-seeking anthropophilic mosquitoes in central Sweden. AB - 1. Blood-seeking diel activity cycles of mosquitoes are described from 24 h landing catches on human bait in a field and a forest habitat during June-August in central Sweden. 2. Daytime activity in the field was low or absent, whilst in the forest activity was relatively even throughout the diel. 3. In both habitats, activity peaks generally occurred about sunset and sunrise and were more distinct in the field than in the forest. 4. Data from this and other studies show that, in general, Aedes cinereus Meigen feeds at night in field-type habitats and Ae.communis (DeGeer) during the diurnal-crepuscular period in forest and woodland habitats. 5. Although abundant in the study area, Anopheles maculipennis Meigen sensu lato, Culex pipiens L., Cx torrentium Martini and Culiseta morsitans (Theobald) were not caught on the human bait. This is because, in central Sweden, An.maculipennis s.l. is mainly feeding in animal sheds whereas the others are ornithophagous. 6. Ae.geniculatus (Olivier) was recorded from central Sweden for the first time. 7. Blood feeding success (proportion of mosquitoes that managed to obtain blood from the human bait) was significantly greater in Ae.cinereus (14.9%) than in Ae.punctor (Kirby), Ae.communis and Ae.annulipes (Meigen) (2.8 0.7%). 8. The data are interpreted in relation to the transmission of Ockelbo disease (caused by Sindbis virus) and tularaemia in Sweden. PMID- 2908784 TI - Evaluation of permethrin-impregnated mosquito-nets against mosquitoes in China. AB - In Yishan County, Guangxi Province, China, where malaria and Brugian filariasis are transmitted by vectors belonging to the Anopheles hyrcanus Pallas group, a study was conducted from June to November 1986 to evaluate the effectiveness of permethrin-impregnated mosquito bednets to reduce man/vector contact. In three experimental villages a total of 246 mosquito nets were treated with permethrin EC at a dosage of 0.5 g/m2. Control bioassays (1 h exposure) of treated nets gave up to 100% mortality of Armigeres subalbatus (Coquillett), Anopheles sinensis Wiedemann and Culex tritaeniorhynchus Giles for up to 19 weeks. During 5 months evaluation in the villages, permethrin-impregnated mosquito-nets reduced the number of mosquitoes found inside nets by 99.3% for Culex quinquefasciatus Say, by 94.4% for Anopheles sinensis Wiedemann and by 75% for Anopheles lesteri anthropophagus Xu & Feng. This measure could thus be considered an appropriate means of controlling vectors in villages. PMID- 2908785 TI - Laboratory experiments on factors affecting oviposition site selection in Toxorhynchites amboinensis (Diptera: Culicidae), with a report on the occurrence of egg cannibalism. AB - Laboratory experiments tested the effects of water quality and the presence of conspecific and heterospecific immatures on oviposition by Toxorhynchites amboinensis (Doleschall). The females showed a highly significant preference for oak leaf infusion water over distilled water. When twenty starved third and fourth instar Tx.amboinensis larvae were present in the water, substantially fewer eggs were counted from pots containing these conspecifics, than from controls in which no larvae were present. Numbers of eggs from pots containing starved second instar larvae did not differ significantly from controls. Observations of larval behaviour while oviposition was occurring suggested that egg numbers were reduced in containers because of egg cannibalism with third and fourth instar larvae, and not because the larvae caused a deterrent effect. Subsequent experiments confirming the occurrence of substantial egg cannibalism by third and especially fourth instar larvae are described. As with larvae, the presence of Tx.amboinensis pupae in the water had little effect on oviposition. If placed in the water 24 h prior to test, pupae very slightly enhanced its attractiveness, but if introduced immediately before test there appeared to be a slight deterrent effect. With heterospecific larvae, twenty fourth instar Ae.aegypti larvae introduced into infusion water 24 h before test rendered the water slightly attractive, while water in which Ae.aegypti larvae had been reared for 48 h proved highly repellent. PMID- 2908786 TI - The functional response of Toxorhynchites rutilus rutilus to changes in the population density of its prey Aedes aegypti. AB - We present an analysis of the functional response of the predator Toxorhynchites rutilus rutilus (Coquillett) to changes in the density of the larvae of Aedes aegypti (L.) (Diptera: Culicidae). The experiment was replicated for five different ages, and at three different densities of the predator. The data were fitted to Rogers' (1972) random predator equation by non-linear least-squares in order to estimate searching efficiency and handling time for each experimental treatment. The data show that estimated searching efficiencies are highest at intermediate ages of the predator for all predator densities tested. Handling time declines exponentially with increasing predator age. There is a marked interference effect; searching efficiency decreases with increased predator density, and this is most pronounced at intermediate prey ages. Estimated handling times increase with predator density at a rate which declines with increasing predator age. PMID- 2908787 TI - Human alveolar macrophage activation: inhibition by forskolin but not beta adrenoceptor stimulation or phosphodiesterase inhibition. AB - Alveolar macrophages are the most numerous cells within human airways. They release inflammatory mediators following immunological challenge and have been implicated in the pathogenesis of asthma. beta-agonists and phosphodiesterase inhibitors are frequently used in the treatment of asthma and are potent inhibitors of human mast cells. We have examined the role of the beta-agonist, isoprenaline, the phosphodiesterase inhibitor Ro-20 1724, and the adenylate cyclase stimulator forskolin on the activation of human alveolar macrophages. This was assessed by monitoring the release of thromboxane B2 (TXB2), leukotriene B4, N-acetyl-beta-D-glucosaminidase (NAG), and superoxide (SO) following stimulation of the cells by opsonised zymosan or IgE/anti IgE complexes. Neither isoprenaline (1nM-10 microM) nor Ro-20 1724 (0.5-50 microM) alone or in combination had any inhibitory effect on release of these mediators. However, forskolin (0.1-100 microM) significantly inhibited release of both TXB2 and SO but not NAG. This result shows that human alveolar macrophages do not possess functional beta-receptors, although stimulation of adenylate cyclase with forskolin, inhibits some of the elements of macrophage activation. PMID- 2908788 TI - Symposium on the assessment of reproductive hazards in the workplace. PMID- 2908789 TI - XIII Symposium Neuroradiologicum. Stockholm, June 23-28, 1986. PMID- 2908790 TI - [Meeting of the XIX European Pancreas Club. Marseilles, 3-5 September 1987]. PMID- 2908791 TI - Hormonal and neurotransmitter interactions in the modulation of memory storage: involvement of the amygdala. AB - This chapter summarizes some of our recent studies examining the memory modulating effects of hormones and drugs affecting adrenergic, noradrenergic and opiate receptor systems. Our findings suggest that the effects of these treatments on memory involve activation of noradrenergic receptors within the amygdaloid complex. And, more generally, the findings support the view that the amygdala is involved in modulating the storage of recent experiences. PMID- 2908792 TI - Ibotenic acid-induced lesions of striatal target and projection neurons: ultrastructural manifestations in dopaminergic and non-dopaminergic neurons and in glia. AB - The cytological changes elicited by central microinjections of the excitotoxin, ibotenic acid (IBO) were examined in the adult rat striatonigral system using electron microscopic immunocytochemistry. The chemical markers included tyrosine hydroxylase (TH), a biosynthetic enzyme in dopaminergic neurons, and glial fibrillary acidic protein (GFAP). Both short (1-7 day) and long (30-60 days) term effects were evaluated at the site of IBO-injections in the striatum and more distally in the substantia nigra, which both contributes afferents and receives efferents from the striatum. In the neostriatum at every survival period examined, TH-labeled axonal processes appeared equally numerous in the control and IBO-injected hemispheres. However, the TH-labeled axons in the striatum ipsilateral to the IBO-injection were slightly enlarged, and generally lacked synaptic densities. In the early period the remaining neuropil showed signs of edema and contained perikarya and dendrites with vacuolar or dense cytoplasm as well as intact, unlabeled terminals. Numerous astrocytes, and apparently demyelinated axons were more commonly seen at the 7 day period. At 30 and 60 days, bundles of myelinated axons, unlabeled axon terminals, and astrocytes containing a variety of cytosomes and other cytoplasmic inclusions were in close apposition to TH-labeled axon terminals. These results suggest that the dopaminergic terminals may serve neuromodulatory functions with respect to glia or other afferent axons remaining after IBO-injections in the striatum. In the substantia nigra, homolateral to the injection, a dense type of degeneration was seen in a few perikarya and dendrites at 7 days of survival. At this stage, electron dense anterograde degeneration also was seen in terminals contacting both TH-labeled and unlabeled dendrites. The secondary long term changes in nuclear groups located distal to the primary lesion are characteristic of certain types of progressive human neuropathological disorders. PMID- 2908793 TI - Potent long-acting alkylated analogs of growth hormone-releasing factor. AB - Analogs of growth hormone-releasing factor-(1-29)-NH2 (GRF-29) involving derivatization with alkyl substituents at the N-terminus, with or without concomitant alkylation of basic amino acids within the peptide chain (lysine in positions 12 and 21), were synthesized using solid-phase methodology and tested for their ability to stimulate growth hormone release in pentobarbital and urethane-anesthetized rats and in 4-day primary cultures of rat anterior pituitary cells. N alpha-MeTyr1-GRF-29 was 40% as potent as GRF-29 15 min after injection of peptide into pentobarbital-anesthetized rats; N alpha-EtTyr1, Nle27 GRF-29 was 5 times more potent and N alpha-iPrTyr1-GRF-29 was 35 times more potent. Combining this latter modification with our previously reported superactive analog modification, D-Ala2, did not appreciably change potency. Analogs with larger alkyl groups, N alpha-cyclohexyl-Tyr1-GRF-29 were not superactive. However, N alpha-benzyl-Tyr1-GRF-29 was 73 times more potent than GRF-29. Most strikingly, the triisopropylated analog N alpha-iPrTyr1, N epsilon iPr-Lys12,21-GRF-29 was 106 times more active. Several analogs were tested in time course assays. All were long-acting as compared to GRF-29, with the triisopropylated analog having the longest duration of activity. In vitro potencies among the analogs with the higher in vivo activities were only slightly increased (2-4 X) with respect to GRF-29. The observed increases in in vivo potencies presumably occur due to enhanced resistance to enzymatic degradation following alkylation or through some other pharmacokinetic effect due to the increased lipophilicity of these analogs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2908795 TI - Diet and behavior: a multidisciplinary evaluation. Proceedings of a symposium. Arlington, Virginia, November 27-29, 1984. PMID- 2908794 TI - Keshan disease--an endemic mitochondrial cardiomyopathy in China. AB - Keshan disease (KD) is a cardiomyopathy endemic in certain areas of China, characterized by severe deterioration and multiple focal necrosis. In the present paper we describe abnormalities of the structure and function of myocardial mitochondria from patients with subacute Keshan disease. Activities of succinate dehydrogenase, succinic oxidase, cytochrome c oxidase, H(+)-ATPase and its sensitivity to oligomycin and the response of membrane potential to energization by ATP were significantly decreased. However, the spectrum of reduced-minus oxidized cytochromes in patients' mitochondria showed no obvious difference in the content of cytochrome c oxidase (aa3). There was also a marked decrease in lipid fluidity of affected mitochondria, and an abnormal amount of moderately electron dense amorphous inclusions. Electron-microscopic x-ray microanalysis and exposure to protein digestion reagent demonstrated that these inclusions are not Ca3(PO4)2, but are, probably, proteinaceous in nature. Affected mitochondria had markedly decreased selenium content. The defects in myocardial mitochondria from patients with chronic Keshan disease were less extensive than those in patients with subacute Keshan disease. We propose that Keshan disease be classified as a form of "mitochondrial cardiomyopathy". PMID- 2908796 TI - Diet and brain function. PMID- 2908797 TI - Neurotransmitter precursors: from animal experiments to human applications. PMID- 2908798 TI - Ways that foods can affect the brain. PMID- 2908799 TI - Effects of carbohydrates on mood and behavior. PMID- 2908800 TI - Biochemical regulation of brain function. PMID- 2908801 TI - [A new case of colitis caused by gold salts]. PMID- 2908802 TI - Procoagulant activity and thrombelastography in Korean hemorrhagic fever. AB - Twenty male patients with Korean hemorrhagic fever were evaluated with thrombelastography (TEG) to assess the changes in coagulation system, and the results were compared with those of conventional coagulation tests. Procoagulant activity in the plasma was determined by comparing the reaction time "r" of the normal plasma and that of the mixture of equal parts of the normal plasma and the patient's plasma. The TEG was found to be a useful measure of the changes in the coagulation profile, and provided instant accurate assessment of the patient's hemostatic function. Presence of the procoagulant activity was demonstrated in the plasma of the patients and indicated occurrence of active intravascular coagulation during the early stage of the disease. PMID- 2908803 TI - Treatment of anxiety with ketazolam in elderly patients. AB - In a multicenter, double-blind trial, 63 elderly patients who had experienced a generalized anxiety disorder for at least one month were randomly assigned to receive 15 mg of ketazolam (n = 31) or placebo (n = 32) daily for 15 days. At the end of this period, if their total scores on the Hamilton Anxiety Rating Scale had decreased by at least 25%, treatment was continued unchanged for a further 15 days. Patients who did not respond to treatment were given an additional 15 mg of ketazolam daily. During the initial 15 days, 83% of the ketazolam-treated patients and 43% of the placebo patients responded to treatment (P < 0.01). During the second 15-day period, the anxiety scores of the ketazolam-treated patients continued to decline significantly, whereas the placebo patients showed no improvement. According to the investigators' assessments of severity of anxiety and patients' ratings of treatment effectiveness, ketazolam was significantly superior to placebo. PMID- 2908804 TI - Properties of [3H]bunazosin binding in rat kidney. AB - Properties of alpha 1-adrenoceptor binding in the renal cortex of rats were studied with [3H]bunazosin as the radiolabeled ligand. Both temperature and incubation time influenced bunazosin receptor binding. Subcellular distribution of [3H]-bunazosin binding revealed that the membrane fraction (30,000 x g pellet) had the largest proportion of total binding sites. Pretreatment of membrane preparation at 56 degrees C for 30 minutes greatly decreased the specific binding of [3H]-bunazosin, though there was no significant effect of the pretreatment at 24 degrees C and 37 degrees C for 30 minutes. Among various cations, some divalent ions such as Cu++ and Zn++ greatly decreased bunazosin binding, whereas monovalent ions had no effect on specific binding. Results of Scatchard analysis suggested that the rat renal cortex membrane has single binding sites with an apparent dissociation constant of 0.38 +/- 0.06 nmol/L, though the rat medulla membrane has no potent binding activity with bunazosin. The displacement study revealed that various adrenergic agents inhibit [3H]bunazosin binding in dose dependent fashion; the rank order of potencies was bunazosin prazosin > phentolamine >> dl-norepinephrine > clonidine, yohimbine >> pindolol, propranolol. These findings reveal that bunazosin has specific receptor binding in the rat renal cortex, indicating that alpha 1-adrenoceptors exist in the rat renal cortex. PMID- 2908805 TI - Effect of age on the pharmacokinetics of orally and intravenously administered terazosin. AB - Terazosin, a new long-acting selective alpha 1-receptor antagonist, was studied in a crossover trial to assess the effect of age on oral and intravenous pharmacokinetics. Thirty healthy male and female volunteers between the ages of 23 and 75 years received 1-mg oral and intravenous doses of terazosin. For both routes of administration, the only pharmacokinetic variables significantly correlated with age were terminal elimination rate constant and the area under the plasma concentration-time curve (AUC). However, the differences in half-life and AUC between the youngest and oldest subjects were modest and not of practical clinical significance. There was no evidence of an enhanced pharmacologic or toxic effect in older subjects. From these data, we conclude that the dosage of terazosin does not need to be adjusted on the basis of age alone; the dose of terazosin is titrated in all patients to the lowest effective dose that is well tolerated. PMID- 2908806 TI - Quicker progress on slow diseases. PMID- 2908807 TI - Somatostatin-like immunoreactivity and somatostatin receptor binding in rat brain in pentylenetetrazol-induced kindling. AB - Kindling was induced in Sprague-Dawley rats by repeated injection of pentylenetetrazol (PTZ, 30 mg/kg, IP). Somatostatin-like immunoreactivity (SLI) and 125I-Tyr-somatostatin binding were measured in different areas of the brain in saline-injected controls, rats receiving PTZ but not kindled (prekindled rats), and kindled rats. Compared to SLI levels in controls, SLI increased (p < 0.01) in the frontal cortex, striatum (p < 0.05 in kindled rats), and hippocampus of both prekindled and kindled animals. Hypothalamic levels of SLI remained unchanged. Compared with the controls, no change was found in somatostatin receptor binding in the frontal cortex, striatum or hippocampus in prekindled or kindled animals. These results suggest that an increased level of somatostatin may be connected to the development and maintenance of kindling. PMID- 2908808 TI - 8th Annual Winter Neuropeptide Conference. Breckenridge, Colorado, January 17-23, 1987. PMID- 2908809 TI - Relationships between the FMRFamide-related peptides and other peptide families. AB - The relationships between peptide families are recognized in terms of structural similarity and immunological and biological activity. Most of the currently known FMRFamide-related peptides (FaRPs) of molluscs were tested in a radioimmunoassay (RIA) and in the two standard bioassays for FMRFamide: the radula protractor muscle of the whelk Busycon contrarium, and the isolated heart of the clam Mercenaria mercenaria. Some peptides were also tested on the heart of the snail Helix aspersa. The responses of the different assays to these peptides were generally similar, but substantial diversity precluded an absolute resolution of relationships, even among molluscan FaRPs. Nevertheless, this set of responses does constitute a standard against which to estimate the relative affinities of putative FaRPs from other animal groups. Many of the non-molluscan FaRPs (e.g., the pancreatic polypeptide-related peptides, gastrin/CCK, and the opioid peptides) are relatively inactive on the molluscan assays, but others (e.g., LPLRFamide, a peptide isolated from chicken brain; the opioid receptor-modulating peptides A18Fa and F8Fa; and gamma 1-MSH) were relatively potent. Several arthropod FaRPs have substantial FMRFamide-like sequence similarity and immunoreactivity, and they may be homologous members of the molluscan peptide family. However, those structural and functional aspects of peptide families that transcend phyletic lines probably reflect basic principles of binding between peptides and membrane proteins rather than homology. PMID- 2908810 TI - Structural aspects of gastrin/CCK-like insect leucosulfakinins and FMRF-amide. AB - The leucosulfakinins (LSKs), isolated from head extracts of the cockroach Leucophaea maderae, are sulfated neuropeptides with homology to gastrin and cholecystokinin. The undecapeptide LSK and decapeptide LSK-II stimulate contractions of the isolated cockroach hindgut. Several structural aspects of the two gastrin/CCK-like insect leucosulfakinins (LSKs) and their relation to FMRF amide are discussed. Replacement of the oxidation sensitive Met residue with isosteric norleucine leads to an analog with retention of biological activity. The Arg residue of the LSKs is critical for cockroach hindgut contractile stimulatory activity, as its introduction into gastrin II transforms the inactive peptide into an active analog. As demonstrated by the equipotent [His14,Arg16]gastrin II, the His8 and Asp5 residues of LSK are not critical for activity. The common C-terminal tetrapeptide of the LSKs ([8-11]LSK) is inactive. Taken together with a comparison of the two LSK structures, the data suggest that the LSK active core resides between [8-11]LSK and [4-11]LSK. This is confirmed by considerable activity displayed by the sulfate analog of LSK-II, which contains an extra sulfate group on the Ser2 residue in the N-terminal region. Homology between the LSKs and molluscan cardioacceleratory and rectum contractile neuropeptide FMRF-amide and Met-enkephalin-Arg6-Phe7 is discussed. The insect LSKs may represent a molecular evolutionary link between the vertebrate gastrin/CCK family and this mammalian enkephalin. PMID- 2908811 TI - Rat intermediate lobe in culture: dopaminergic regulation of POMC biosynthesis and cell proliferation. AB - The effects of the selective D-2 selective agonist, quinpirole, on biosynthesis of proopiomelanocortin (POMC) and cell proliferation rate of cultures of rat intermediate lobe (IL) have been examined. Primary cultures of rat IL were prepared by mechanically dispersing IL lobules in medium. Following a six day incubation, approximately 25% of the cells settled onto the culture plate and began to extend into a monolayer. Quinpirole markedly reduced immunoreactive beta endorphin levels in the medium and POMC mRNA in both the attached and floating lobules. The incorporation of 35S-methionine into 32 kDa POMC, a 18-22 kDa complex of proteins, a 16 kDa protein and a 15 kDa protein was decreased significantly in both the attached and floating lobules. In contrast, the proliferation in the floating, but not the attached, cells was inhibited by quinpirole. The floating IL lobule appears to provide a reasonably faithful model of the dopaminergic regulation of IL function in vivo, while the attached IL cells may provide an interesting tool to study the regulation of IL cell proliferation. PMID- 2908812 TI - Somatostatin inhibits the secretion of bombesin-like peptides from small cell lung cancer cells. AB - The effects of somatostatin (SRIF) on small cell lung cancer (SCLC) cell line NCI H345 was investigated. SRIF had no effects on the basal cAMP levels or the secretion rate of bombesin-like peptides. VIP (1 microM) increased the cAMP levels approximately 10-fold and the secretion rate of bombesin-like peptides 3 fold. SRIF and its analogues inhibited the increase in the cAMP levels and the secretion rate of bombesin-like peptides caused by VIP. The order of peptide potency was (D-Trp8)SRIF > SRIF-28 = (Tyr11)SRIF > SRIF. These data suggest that functional SRIF receptors may be present on SCLC cells. PMID- 2908813 TI - Co-localization of IGF-II receptors, IL-1 receptors and Thy 1.1 in rat brain. AB - The distribution of 125I-IGF-II and 125I-IL-1 binding to rat brain sections was determined with autoradiography, Thy 1.1 with radioimmunocytochemistry. The pattern of distribution of all three was found to be identical and almost the same as the pattern achieved by a Nissl stain. In preliminary studies excess IGF II was shown to inhibit the binding of radiolabeled IGF-II and IL-1 but not anti Thy 1.1. Similarly, IL-1 inhibited the binding of radiolabeled IL-1 and IGF-II but not anti-Thy 1.1. Anti-Thy 1.1 inhibited the binding of IGF-II and IL-1, but was not inhibited by either IGF-II or IL-1. The distribution data from this study indicates the IGF-II receptors, IL-1 receptors and Thy 1.1 are present on almost all neurons in the brain. The preliminary competition studies suggest that these factors may, under some conditions, function in a common biochemical cellular process to regulate each other's functions. Both IGF-II and IL-1 are growth factors and Thy 1.1 may play a role in synapse formation and cell adhesion. Perhaps, among other things, these growth factors and Thy 1.1 function in the development and maintenance of intercellular contacts within the brain. PMID- 2908814 TI - Cardiovascular responses in healthy subjects to a novel oral dopamine agonist, fenoldopam. AB - Two double-blind randomized crossover studies were carried out in healthy male subjects to determine the cardiovascular effects of fenoldopam and to assess whether they could be modified by metoclopramide. Blood pressure (BP) and heart rate (HR) were measured supine and upright, before and for up to 4 h after dosing. Single oral doses of fenoldopam 50, 100 or 150 mg or placebo were administered in one study. In the other study, subjects received 20 mg metoclopramide or placebo intravenously, 20 min before an oral dose of 100 mg fenoldopam or placebo. Fenoldopam produced decreases in diastolic BP and increases in HR indicative of an orally active systemic arteriolar vasodilator. Mean peak responses occurred 30-60 min after dosing and values had returned to pretreatment levels within 3-4 h. The decrease in diastolic BP was partially attenuated by pretreatment with metoclopramide. Thus, at least in part, the fall in BP following fenoldopam could be due to an interaction with dopamine receptors. PMID- 2908815 TI - Human vasodilator responses to a dopamine agonist: possible mechanisms. AB - The action of fenoldopam, a selective dopamine DA1 agonist, on resting forearm blood flow was studied in healthy male volunteers by venous plethysmography. Metoclopramide and (+/-) sulpiride were used as dopamine antagonists. Intra arterial fenoldopam over the range (100 ng/min to 1 microgram/min) produced a dose-related increase in forearm blood flow without evidence of systemic effects. The response to fenoldopam was not antagonized by metoclopramide or (+/-) sulpiride and neither antagonist alone altered resting forearm blood flow. It is unclear whether the effects of fenoldopam in the forearm vasculature are mediated through the vascular dopamine receptor. PMID- 2908816 TI - Celiprolol, a potent cardioselective beta 1-adrenoceptor antagonist with mild alpha 2-adrenoceptor antagonist properties. AB - Celiprolol is a cardioselective beta-adrenoceptor antagonist, with interesting propranolol-insensitive cardiostimulatory, vasodilatory and bronchodilatory effects. Recent reports suggest that mild alpha 2-adrenoceptor antagonism may contribute to these effects. The present investigation further explored the alpha 2 effects of celiprolol. In isolated electrically-stimulated rat atria celiprolol (1.0 and 10 mumol/l) significantly increased the release of [3H]-norepinephrine, consistent with the blockade of pre-junctional alpha 2-adrenoceptors. Evidence for post-synaptic alpha 2-adrenoceptor antagonist activity was obtained in studies of the effects of celiprolol on the pressor response to clonidine and either phenylephrine or methoxamine in perfused hind-limbs of dogs (pretreated with mecamylamine and propranolol) and pithed rats. In the dog, celiprolol (10 mg/kg) significantly inhibited the vasoconstrictor response of clonidine while in the rat higher doses were required (> or = 12.5 mg/kg). Celiprolol did not affect the pressor response induced by alpha 1-agonists. We conclude that celiprolol possesses a mild alpha 2-adrenoceptor blocking action which may contribute to its unconventional profile. PMID- 2908817 TI - Effects of beta-receptor blockade on carbohydrate metabolism. AB - The effects of beta-blockers on glucose tolerance, insulin secretion and peripheral insulin sensitivity were evaluated by oral glucose tolerance test and euglycaemic insulin technique in six normoglycaemic patients with primary arterial hypertension at the end of 3-week treatments with placebo (one tablet twice daily) and propranolol (80 mg twice daily). Body weight did not change during the study (83 kg at the end of placebo, 83 kg at the end of propranolol), while blood pressure (150 +/- 9/97 +/- 8 mmHg on placebo, 138 +/- 8/89 +/- 8 mmHg on propranolol, P < 0.01) and heart rate (66 +/- 9 beats/min on placebo, 60 +/- 5 beats/min on propranolol, P < 0.05) showed a significant fall on the beta blocker. No change was observed in glucose tolerance (incremental area for glucose 3462 +/- 1149 mg/dl per min on placebo, 3209 +/- 1695 mg/dl per min on propranolol), insulin secretion (incremental area for serum insulin 7579 +/- 4380 microU/ml per min on placebo, 7934 +/- 4351 microU/ml per min on propranolol) and peripheral insulin sensitivity (metabolic clearance rate 11 +/- 4 ml/kg per min on placebo, 13 +/- 6 ml/kg per min on propranolol). These data support the hypothesis that chronic treatment with adrenergic blocking agents does not induce any significant change in insulin secretion or peripheral insulin sensitivity. PMID- 2908818 TI - Cardiovascular effects of short-term selective alpha 1-adrenergic blockade with terazosin in patients with essential hypertension. AB - The effects of selective alpha 1-adrenergic blockade with the agent terazosin on blood pressure and cardiovascular pressor responsiveness as related to major pressor factors were assessed in 17 patients with mild to moderate essential hypertension (mean age +/- s.e.m. 48 +/- 2 years). As compared with a 2-week placebo period, terazosin, given during 8 weeks at a maximal daily dose of 10.5 +/- 1.7 mg, caused a fall of supine arterial pressure (from 153/103 +/- 3/2 to 143/96 +/- 4/2 mmHg; P < 0.05), and a marked blunting of cardiovascular pressor responsiveness to norepinephrine (NE) as judged from the pressor dose (from 0.43 +/- 0.05 to 12.74 +/- 2.93 mmol/kg per min, P < 0.05) and from the shift to the right (P < 0.01) of the correlation relating NE-induced increments of arterial pressure to the corresponding increases of plasma NE during NE infusion. Heart rate, body weight, exchangeable sodium, blood volume, NE plasma clearance, plasma epinephrine, renin, angiotensin (ANG) II and aldosterone levels, the relationships between the ANG II-induced increases in arterial pressure or plasma aldosterone and the concomitant increments of plasma ANG II during ANG II infusion as well as the heart rate responsiveness to isoproterenol did not change significantly after terazosin. The findings of the present study suggest that the fall of arterial pressure induced by selective alpha 1-adrenergic blockade in patients with essential hypertension is associated and probably explained by inhibition of alpha 1-mediated, noradrenergic-dependent vasoconstriction. PMID- 2908819 TI - Does beta 1-selective agonistic activity interfere with the antihypertensive efficacy of beta 1-selective blocking agents? AB - In order to investigate whether addition of beta 1-selective agonism can interfere with the antihypertensive efficacy of beta 1-selective adrenoceptor blockers, two separate studies were carried out to evaluate the effects on blood pressure and heart rate of three beta 1-selective blockers with or without varying degree of beta 1-selective agonism. In hypertensive patients at rest, the greatest blood pressure reduction and bradycardia were found with atenolol, a beta 1-selective blocker without any agonistic activity; a consistently smaller effect on blood pressure and heart rate was observed with Visacor (ICI 141 292), a beta 1-selective blocker with moderate beta 1-selective agonism, whereas no clinically relevant decrease in blood pressure occurred with Corwin (ICI 118 587), the beta 1-selective blocker with high beta 1-selective agonism. In contrast, during exercise-induced sympathetic activation, all three compounds reduced systolic blood pressure and heart rate to a similar degree. PMID- 2908820 TI - Compound ICI 118,551, a beta 2-adrenoceptor antagonist, lowers blood pressure. AB - Adrenaline may increase noradrenaline release and enhance sympathetic pressor effects through activation of pre-synaptic beta 2-adrenoceptors. Conversely, blockade of beta 2-receptors could lead to a fall in blood pressure. To test this hypothesis we performed a double-blind placebo controlled crossover study in nine patients with mild hypertension, comparing the effects of the beta 2-selective blocker ICI 118,551, 50 mg t.i.d. with those of propranolol, 80 mg t.i.d. Two hours after the first dose of ICI 118,551 or propranolol, plasma noradrenaline and blood pressure remained unchanged while heart rate and renin were reduced. After 1 week, blood pressure was significantly reduced by both drugs. The beta 2 selectivity of ICI 118,551 was confirmed by isoprenaline infusion studies. After 1 week of treatment ICI 118,551 had no effect on the beta 1-receptor mediated shortening of electromechanical systole (QS2I), the rise in systolic pressure and rise in renin, whereas these responses were blocked by a dose factor of eight after propranolol. ICI 118,551 and propranolol equally blocked the beta 2 receptor mediated fall in diastolic pressure and the rise in noradrenaline. We conclude that beta 2-selective blockade by ICI 118,551 lowers blood pressure. This finding is compatible with a role of pre-synaptic beta 2-receptors in blood pressure control. PMID- 2908821 TI - Comparison of calcium antagonists with other antihypertensive agents. AB - The demonstration that antihypertensive drug treatment reduces mortality and morbidity in mild hypertension has extended the indications for treatment. Verapamil, nitrendipine, angiotensin converting enzyme inhibitors and beta adrenoceptor blocking drugs are all equally effective in reducing blood pressure. The choice of drug depends on the presence or absence of specific contra indications and the occurrence of side effects in individual patients. PMID- 2908822 TI - Alpha 1- and alpha 2-adrenoceptor mediated vasoconstriction in the forearm: differences between normotensive and hypertensive subjects. AB - Alpha 1- and alpha 2-adrenoceptor mediated vasoconstriction were compared between 13 patients with essential hypertension and 13 normotensive controls, matched for age and sex. For this purpose changes in forearm blood flow induced by infusion of the selective alpha 1-adrenoceptor agonist methoxamine, the selective alpha 2 adrenoceptor agonist B-HT 933, the catecholamines adrenaline and noradrenaline and the alpha 2-adrenoceptor antagonist yohimbine were measured in both study groups. The catecholamines were infused together with propranolol to avoid beta adrenergic effects. Forearm blood flow was measured by plethysmography. All agonists produced a dose-dependent vasoconstriction which was more pronounced in the hypertensive subjects but no preference was found for either the alpha 1- or alpha 2-adrenoceptor mediated vasoconstriction. Yohimbine induced a greater vasodilatation in the normotensive subjects. The greater vasoconstriction in the hypertensive patients could be explained by structural vascular changes. No evidence was found for an important role of alpha 2-adrenoceptor mediated vasoconstriction in essential hypertension. PMID- 2908823 TI - [International Symposium on Occupational Injury of the Ulnar Nerve. Frauenau, 9 11 June 1985]. PMID- 2908824 TI - Differential tumor growth of blood-borne B16 melanoma variants in cerebral dura mater is related to tumor-host cell reactions. AB - Intracarotid injection of B16-B14b or B16-B15b melanoma cells, previously established from B16-F1 melanoma by in vivo selection fourteen- or fifteen-times, respectively, for brain surface colonization, preferentially produced tumor nodules in mice at brain surface sites, most frequently in the dura mater, followed by the leptomeninges and cerebral cortex. There was a marked difference, however, in tumor growth at these sites using the two B16 sublines. Intracarotid injection of B16-B14b cells rarely produced visible tumors, whereas B16-B15b cells formed deeply pigmented tumors up to 7 mm in diameter in the brain menings of almost all mice examined. Histologic and electron microscopic investigation revealed that B16-B14b tumors evoked dramatic immunocyte cell infiltration and granulomatous reactions, while B16-B15b tumors were accompanied by much less tumor-host cell reactions. Splenectomy or laparotomy 1-2 weeks before or after intracarotid injection of B16-B14b cells dramatically enhanced tumor growth in the dura mater without extensive tumor-host cell reactions. The results suggest that the differential growth of B16-B14b and B16-B15b tumor cells in the cerebral dura mater is based, in part, on the abilities of these melanoma cells to elicit host cell reactions. PMID- 2908825 TI - Dynamic heterogeneity: experimental metastasis studies with RIF-1 fibrosarcoma. AB - We have examined the metastatic behaviour of cells from a series of clones of RIF 1 fibrosarcoma, a recently derived murine tumour. The clones were grown to different sizes (small: 10(5)-10(6) cells and large approximately 2 x 10(7) cells) and their metastatic potential was quantified using an experimental metastasis assay. There was significant variability between the metastatic potential of clones derived from the same population. Furthermore large clones had higher metastatic efficiency (metastases/cell injected) than the small clones derived from the same population. The results from these experiments indicate that metastatic variants are generated during the growth of the clones. The mean effective rate of generation of metastatic variants was estimated using Luria Delbruck fluctuation analysis to be 1.7 x 10(-5)/cell/generation. The data described are consistent with a dynamic heterogeneity model of metastasis, in which the variant phenotypes are postulated to arise in growing tumour cell populations at a high rate but need not be stable in order to produce metastases. The results thus indicate that the model is applicable to a recently derived tumour as well as the extensively transplanted KHT sarcoma, B16 melanoma and OTF9 embryonal cell carcinoma. PMID- 2908826 TI - Inhibition of tumor metastasis by carrageenan-induced granulomas. AB - At -1, 0, +1 weeks from tumor inoculation, carrageenan-impregnated cotton sponges were subcutaneously implanted. Tumor BN472, a malignant adenocarcinoma, was transplanted in syngeneic Brown Norway female rats, either subcutaneously or intravenously. Plasma eicosanoid values (prostaglandin-E2, thromboxane-B2 and 6 keto-prostaglandin-F1 alpha) were determined as well as the cellular immune response (natural killer activity, concanavalin-A and phytohemagglutinin stimulation of spleen lymphocytes). Primary tumor growth and the number of tumor foci in the lungs were measured as parameters of tumor growth and dissemination. No statistically significant differences were observed in primary tumor growth. However, the number of metastatic foci in the lungs of rats in which the tumor was implanted subcutaneously, as well as those in which the tumor was inoculated intravenously, was significantly reduced in those that had carrageenan implanted one week after tumor inoculation. In all other carrageenan-treated groups only slightly reduced numbers of metastatic foci were seen. In those rats with a decreased number of tumor metastatic foci in the lungs, no correlation could be shown with either altered plasma prostaglandin levels, or cellular immune response. PMID- 2908827 TI - B16 melanoma spontaneous brain metastasis: occurrence and development within leptomeninges blood vessels. AB - Subcutaneous tumors initiated with mouse B16 melanoma clones G3.5 and G3.12 disseminated visible spontaneous brain metastases in 67 per cent and 32 per cent, respectively, of mice with extensive lung metastasis. Most brain metastases appeared as pigmented emboli within blood vessels of the leptomeninges overlying the cerebral cortex. Intravascular metastases consisted of tumor cell aggregates surrounded by fibrous material and generally contained viable cells that proliferated in culture. Some metastatic emboli apparently proliferated intravascularly to such an extent as to cause vessel disruption, permitting tumor invasion into the adjacent cerebral cortex. Cultured cells from G3.12 leptomenings metastases produced tumors that metastasized to a much greater extent than unselected G3.12 tumors, but brain metastasis still occurred only secondarily, after initial dissemination to the lungs. In contrast, G3.5 brain metastasis-derived populations formed tumors that ultimately metastasized to the brain to lesser extents than did unselected G3.5 tumors. One selected variant, G3.12/BM2, reproducibly formed visible and viable brain metastases in more than 80 per cent of tumor-bearing mice, and lethal or potentially lethal brain metastases in 10-15 per cent of mice. This variant may serve as a model for clinical brain metastasis. PMID- 2908829 TI - Classification of pancreatitis. AB - The diagnosis of acute and chronic pancreatitis should be made by histopathology, but this is usually impossible. Thus, the classification system proposed by the Cambridge and Marseille Symposia must suffice at the present time. Acute Pancreatitis: Diagnostic Criteria. 1. An elevation of plasma levels of pancreatic enzymes greater than ten standard deviations above the laboratory normal. 2. Evidence of acute pancreatitis from imaging, laparotomy, and/or autopsy. Clinical Classification. 1. Etiology where known (if unknown, this should be stated). 2. Degree of severity: (a) mild (no multisystem failure and uncomplicated recovery); (b) severe (multisystem failure and/or development of a complication that should be stated, for example, pseudocyst). Chronic Pancreatitis: Diagnostic Criteria. 1. Permanently impaired exocrine pancreatic function tests (greater than two standard deviations below the normal for the test). 2. Permanent morphological change in the gland. Clinical Classification. 1. Etiology where known (if unknown, this should be stated). 2. Pain present or absent. 3. Degrees of severity (mild, moderate, or severe changes in morphology and/or function). 4. COMPLICATIONS: cysts, portal hypertension, diabetes mellitus, and so forth. PMID- 2908828 TI - Organ distribution of experimental metastases of a human colorectal carcinoma injected in nude mice. AB - The metastatic behavior of the HT-29 human colorectal carcinoma cell line was studied following injection into nude mice by different routes. After intrasplenic injection, experimental metastases formed in the livers of most mice. Variant lines were established in culture from the liver lesions and from tumors growing at the site of injection, the spleen. Cells of the HT-29 LMM line exhibited slightly enhanced ability to form liver metastases compared with cells of the non-selected parent line. When injected i.v., the HT-29 cells produced only a few small experimental metastases in the lungs, but in most of the mice macroscopic tumors were found in various lymph nodes and the interscapular fat. Analyses of the distribution of IdUrd-labeled cells did not reveal a preferential localization of the HT-29 cells in sites where metastases subsequently formed. This suggested that the growth of the human colon carcinoma cells in those sites might be the result of a stimulatory interaction between the tumor and host cells as opposed to growth in sites such as the lungs, where numerous cells arrested after i.v. injection but only a few, small metastases were seen 60 days later. PMID- 2908830 TI - Dopamine effects on diaphragmatic strength during acute respiratory failure in chronic obstructive pulmonary disease. AB - STUDY OBJECTIVE: To assess the effects of dopamine, which has an inotropic effect on the myocardium and increases renal and splanchnic blood flow, on diaphragmatic contraction. DESIGN AND PATIENTS: We studied the changes in transdiaphragmatic pressure during electrical bilateral supramaximal stimulation of the phrenic nerves in eight patients with chronic obstructive pulmonary disease during acute respiratory failure. In three patients, changes in diaphragmatic blood flow were also evaluated. METHODS: All patients were intubated and artificially ventilated. Stimulated transdiaphragmatic pressure, cardiac output, evaluated with a Swan Ganz catheter, and diaphragmatic blood flow, evaluated by timed volume collections of left phrenic venous effluent (a catheter was introduced into the right femoral vein and advanced into the left inferior phrenic vein) were measured before dopamine infusion, every 10 minutes after the onset of dopamine infusion (10 micrograms/kg body weight.min during 30 minutes) and 15 minutes after the end of dopamine infusion. Arterial blood gases and pH were measured before and at the end of dopamine infusion. MEASUREMENTS AND MAIN RESULTS: Arterial blood gases and pH were maintained within normal range by mechanical ventilation throughout the study. With dopamine infusion, heart rate increased by 17% (P less than 0.001) and cardiac output by 40% (P less than 0.001) on the average. The increase in cardiac output was accompanied by a marked increase in diaphragmatic blood flow (30% on the average) in the three patients in whom it was measured (P less than 0.001). Diaphragmatic strength also increased significantly during dopamine administration. Transdiaphragmatic pressure for an identical phrenic stimulation increased by 30% (P less than 0.001) on the average. The changes in cardiac output, diaphragmatic blood flow, and transdiaphragmatic pressure persisted throughout the infusion period; all values returned to control values 15 minutes after the end of dopamine administration. CONCLUSIONS: Dopamine has a potent effect on diaphragmatic strength generation and diaphragmatic blood flow in patients with chronic obstructive pulmonary disease during acute respiratory failure. It is possible to improve diaphragmatic contraction in these patients by administering pharmacologic agents that augment diaphragmatic blood flow. PMID- 2908831 TI - Zidovudine-induced hepatotoxicity. PMID- 2908833 TI - Methotrexate and rheumatoid arthritis. PMID- 2908832 TI - Reversal of adrenal glucocorticoid dysfunction in a patient with disseminated histoplasmosis. PMID- 2908834 TI - Coagulase-negative staphylococcal bacteremia. Mortality and hospital stay. AB - OBJECTIVE: To determine the attributable mortality and the excess length of hospital stay resulting from coagulase-negative staphylococcal bacteremia. DESIGN: Matched historical cohort study. SETTING: Large university-based tertiary care center. PATIENTS: Of 171 patients with hospital-acquired coagulase-negative staphylococcal bacteremia identified by prospective surveillance of nosocomial infections from 1 July 1984 to 30 June 1987, 118 met criteria for the study and were matched to a control patient by age, sex, primary diagnoses, operative procedures, and date of admission. MEASUREMENTS AND RESULTS: Success was achieved in 621 of 650 (96%) variables used for matching. Staphylococcus epidermidis accounted for 92% of the bacteremias. Twenty cases (17%) had evidence of septic shock, and 10 had disseminated intravascular coagulation. The mortality rate in cases was 36 of 118 (30.5%) compared with 20 of 118 (16.9%) in controls. The attributable mortality was 13.6% (95% CI, 4.2 to 22.9) and the risk ratio for dying was 1.8 (95% CI, 1.2 to 2.7; P = 0.006). The median length of stay was 46 days for cases and 37.5 for controls (P = 0.0002). CONCLUSIONS: Coagulase negative staphylococci, the leading organisms causing hospital-acquired bacteremias, are associated with mortality in excess of that due to the underlying diseases alone. Moreover, they significantly prolong the length of hospital stay. These findings show the importance of coagulase-negative staphylococcal bacteremia in hospitalized patients. PMID- 2908835 TI - Cocaine and rhabdomyolysis. PMID- 2908836 TI - Nodular pneumonitis after cancer chemotherapy. PMID- 2908837 TI - Cardiac effects of inhaled typewriter correction fluid. PMID- 2908838 TI - Thrombotic thrombocytopenic purpura and human T-lymphotrophic virus, type 1 (HTLV 1) PMID- 2908839 TI - Syngeneic anti-idiotype monoclonal antibodies to murine anticarcinoembryonic antigen monoclonal antibodies. AB - BALB/c mice were immunized with either NP-3 or NP-4, two anticarcinoembryonic antigen murine monoclonal antibodies. Each animal produced anti-idiotype antibodies to the corresponding immunogen and no cross-reactivity between anti-NP 3 sera and anti-NP-4 sera was detected. Hybridomas were produced from these animals and two IgG1 anti-idiotype monoclonal antibodies were obtained: CM1 specific for NP-3 and CM11 specific for NP-4. CM1 and CM11 recognized determinants located within the antibody-combining site, since each anti-idiotype antibody inhibited the binding between the corresponding idiotype and carcinoembryonic antigens. Using an immunoblotting technique, neither CM1 nor CM11 reacted with isolated heavy or light chains of NP-3 or NP-4, whereas binding was observed with the intact molecule. This observation indicates that CM1 and CM11 are directed against conformational idiotypes resulting from the association of the variable regions of the heavy and light chains. Taken together, these results suggest that CM1 and CM11 might bear internal images of carcinoembryonic antigen epitopes, and that they are potential candidates as idiotype vaccines against colorectal tumors. PMID- 2908840 TI - Cytotoxicity and DNA damage caused by the azoxy metabolites of procarbazine in L1210 tumor cells. AB - Procarbazine, a chemotherapeutic hydrazine, is thought to be metabolized to an alkylating species similar to methyl carbonium ion by multistep reactions involving cytochrome P-450, monoamine oxidase, and cytosolic enzymes. The DNA damaging and cytotoxic potential of procarbazine and its metabolites in murine L1210 leukemia tumor cells in vitro was determined using alkaline elution techniques and extrapolation of growth curves. Neither procarbazine nor any of the chemical degradation products (except for the aldehyde derivative at high concentrations) caused significant amounts of DNA strand breakage. The primary enzymatic oxidation product, azo-procarbazine, did not produce strand breakage. However, exposure of the cells to either of the two isomers of azoxy-procarbazine led to significant DNA damage and cytotoxicity. DNA damage included both single strand breaks and alkali-labile sites. At equimolar concentrations, the azoxy 2 isomer of procarbazine caused 14 to 20 times more DNA damage than did the azoxy 1 metabolite. When cell growth is expressed as percentage survival of L1210 cells, the azoxy 2 isomer was approximately 7-fold more toxic than the azoxy 1 metabolite. The other metabolites tested showed little or no cytotoxicity. L1210 cells were shown to contain little or no cytochrome P-450 or monoamine oxidase activity, which may account for the lack of toxicity of the parent drug or the primary oxidative metabolite, azo-PCZ, to these cells. The conversion of procarbazine to the azoxy-procarbazine isomers in vivo must occur in cells which contain these enzymes, such as liver. However, the azoxy isomers of procarbazine were metabolized in L1210 cells, presumably leading to the DNA or cytotoxic damage observed. PMID- 2908841 TI - Metabolism of retinol and retinoic acid in N-methyl-N-nitrosourea-induced mammary carcinomas in rats. AB - This study was conducted to examine the in vivo uptake and metabolism of natural retinoids by N-methyl-N-nitrosourea-induced mammary carcinomas. In this study, endogenous retinol and retinyl esters were present in normal mammary epithelial cells, but were undetectable in N-methyl-N-nitrosourea-induced mammary carcinomas in rats as determined by high-pressure liquid chromatography. No differences were found in plasma levels of retinol, in liver retinyl esters, or total content of vitamin A between tumor-bearing and control animals. Administered labeled retinol was taken up and esterified by normal mammary epithelial cells. Tumor-bearing rats were given injections i.p. of either [3H]retinol or [3H]retinoic acid. Radioactivity increased progressively with time in liver and other tissues except in breast tumor, where the uptake fluctuated over the 8 days after the injection of [3H]retinol; in mammary tumors practically no metabolism of [3H]retinol occurred, while in other tissues extensive esterification was detectable. In contrast, in animals given injections of [3H]retinoic acid, the uptake and metabolism of the label in the breast tumors paralleled with those found in other tissues. Neither the activity of acyl coenzyme A:retinol acyl transferase nor the activity of retinyl ester hydrolase was altered in the mammary tumor compared to the normal mammary gland. On the other hand, a significant decrease in the retinal oxidase activity was found in tumor tissue compared to normal mammary tissue. Since no esterification of [3H]retinol occurred in vivo despite the presence of acyl coenzyme A:retinol acyl transferase activity, it is possible that a specific defect in the cellular uptake of retinol may exist in N-methyl-N nitrosourea-induced mammary carcinomas. PMID- 2908842 TI - Characterization of DNA damage and cytotoxicity induced in two human colon carcinoma cell lines by cyclodisone. AB - Cyclodisone is an active alkylating antitumor agent that is being considered for Phase 1 clinical trials in humans and is currently undergoing toxicological evaluation. Cyclodisone was found to be more toxic to human colon carcinoma cells of the Mer- phenotype (BE) than cells of the Mer+ phenotype (HT-29). DNA interstrand cross-links were observed in the sensitive cell line but only at concentrations which were extremely toxic. No DNA interstrand cross-links were observed in the resistant cell line. Total DNA cross-links, which reflect both DNA interstrand and DNA-protein cross-linking, were observed in either cell type but were greater in quantity and persisted longer in the sensitive BE cell line, when compared to those produced in the resistant HT-29 cell line. DNA strand breaks were also observed in both cell types and were found to be protein associated. The mechanism of action of cyclodisone would appear to be related to the presence of total DNA cross-links and might involve an, as yet, unidentified DNA-protein interaction. PMID- 2908843 TI - Human DNA damage induced by 1,2,4-benzenetriol, a benzene metabolite. AB - Reactivities of benzene metabolites (phenol, catechol, hydroquinone, 1,4 benzoquinone, 1,2,4-benzenetriol) and related polyphenols (resorcinol, pyrogallol, phloroglucinol) with DNA were investigated by a DNA sequencing technique using 32P 5'-end-labeled DNA fragments obtained from human c-Ha-ras-1 protooncogene, and the reaction mechanism was studied by UV-visible and electron spin resonance spectroscopies. 1,2,4-Benzenetriol caused strong DNA damage even without alkali treatment. Alkali-labile sites induced by 1,2,4-benzenetriol were base residues of guanine and adjacent thymine. Catalase, superoxide dismutase and methional inhibited the DNA damage completely, but sodium formate did not inhibit it. 1,2,4-Benzenetriol-induced DNA damage was inhibited by the addition of a Cu(I)-specific chelating agent, bathocuproine, and was accelerated by the addition of Cu(II). The addition of Fe(III) did not create any significant effects on 1,2,4-benzenetriol-induced DNA damage. Electron-spin resonance studies using spin traps demonstrated that addition of Fe(III) increased hydroxyl radical production during the autoxidation of 1,2,4-benzenetriol, whereas the addition of Cu(II) did not. The results suggest that DNA damage was caused by an unidentified active species which was produced by the autoxidation of 1,2,4-benzenetriol in the presence of Cu(II), rather than by hydroxyl radicals. The possibility that 1,2,4-benzenetriol-induced DNA damage is one of the primary reactions in carcinogenesis induced by benzene is discussed. PMID- 2908844 TI - Modulation of murine natural killer cells by a granulocytosis-inducing tumor. AB - The nonmetastatic neutrophilia-inducing murine mammary carcinoma CE1460 has been shown previously to have profound effects on hemopoiesis and lymphopoiesis. In this report we examined the effects of progressive growth of CE1460 on natural killer (NK) cell activity both in the bone marrow, the site of primary NK cell production, and in a peripheral site, the spleen. (BALB/c x CE)F1 mice were injected subcutaneously with trypsinized cells from in vivo passaged CE1460 or from B66, a BALB/c mammary carcinoma that does not induce neutrophilia. 3 days posttumor implantation, NK activity in bone marrow cells or spleen cells was greatly enhanced compared to normal controls. In B66 tumor-bearing mice, NK activity returned to normal by Day 7 and remained there through Day 14. In contrast, however, NK activity in CE1460 tumor-bearing mice decreased to only 10 20% of normal by Day 14. Excision of the tumor on Day 14, when WBC counts were three times normal, was followed by a rapid return of the WBC count to the normal range. NK activity in bone marrow and in spleen cells recovered somewhat but was still significantly suppressed 7 days after tumor excision. Limiting dilution analysis revealed a 3-5-fold decrease in frequency of NK precursors in bone marrow cells of mice bearing CE1460 for 7 or 14 days. The dramatic changes in NK activity observed in these experiments may reflect perturbation in production as well as an initial activation and subsequent suppression of mature NK cells. PMID- 2908845 TI - Two human monoclonal antibodies reacting with the major gangliosides of human melanomas and comparison with corresponding mouse monoclonal antibodies. AB - The fine specificity analysis of two human monoclonal antibodies (AbFCM1 and AbHJM1) reacting with gangliosides is described and their specificities are compared with analogous mouse monoclonal antibodies (mAbs). These two antibodies were generated from lymphocytes of melanoma patients by Epstein-Barr virus transformation followed by fusion with mouse myeloma NS-1. Using a wide variety of gangliosides, including N-glycolylneuraminic acid (NeuGc)-containing compounds, the precise structures recognized by these two antibodies were elucidated by enzyme-linked immunosorbent assay and immunostaining of thin-layer chromatograms. AbFCM1 reacted with N-acetylneuraminic acid (NeuAc)-type GM3, GD1a, sialylparagloboside, and GT1b in decreasing order of intensity. This antibody also reacted with (NeuAc-NeuGc-)-GD3 and -disialylparagloboside, but did not react with NeuGc-type GM3, GM2, sialylparagloboside, (NeuGc)2-GD3 and disialylparagloboside. The main epitope structures recognized by AbFCM1 are, therefore, NeuAc alpha 2----3Gal beta 1- and NeuAc alpha 2----8NeuGc alpha 2--- Gal beta 1-. These results are similar to the specificity of mouse mAb M2590. AbHJM1 reacted with NeuAc-type GD3 and disialylparagloboside, GD2, GD1b, GM3, and GT1b, in decreasing order of intensity. Among NeuGc-type gangliosides, this antibody reacts with (NeuAc-NeuGc-)-GD3 and -disialylparagloboside, but did not react with gangliosides containing only NeuGc. Consequently the epitope structure recognized by AbHJM1 is probably (R)-(NeuAc alpha 2----8Sialic acid alpha 2--- 3)Gal beta 1-. Mouse anti-GD3 mAbR24, in contrast, showed strong reactivity only with GD3 and -disialylparagloboside among NeuAc-type gangliosides, but showed a similar pattern to AbHJM1 in its reactivity with NeuGc-containing gangliosides. Although these two human monoclonal antibodies are not highly restricted in their specificities, they reacted best with the major gangliosides, GM3 and GD3, present in the majority of human melanomas. PMID- 2908846 TI - Expression of Tn, sialosyl-Tn, and T antigens in human colon cancer. AB - Mucin glycoproteins are major secretory products of the colon and contain O linked oligosaccharides synthesized on a polypeptide backbone. The initial step in the synthesis of O-linked oligosaccharides is the addition of N acetylgalactosamine to serine or threonine residues forming the Tn antigen. This substance can then receive additional carbohydrate residues such as sialic acid to form sialosyl-Tn antigen, or galactose to form T antigen. In the colon, the T antigen is an oncodevelopmental cancer-associated antigen but little is known about Tn and sialosyl-Tn expression. The present comparative immunohistochemical study was performed to analyze the expression of these antigens in fetal, normal adult, and malignant colorectal tissues with an aim toward elucidating whether Tn and sialosyl-Tn are also oncodevelopmental colon cancer-associated antigens and to gain insight into the earliest steps of mucin glycosylation in colonocytes. We used three reagents to detect Tn antigen (two monoclonal antibodies ETn1.01 and CU-1, and one lectin Vicia villosa), two reagents to detect sialosyl-Tn (monoclonal antibodies TKH2 and B72.3) and one to detect T antigen (monoclonal antibody AH9-16). Except for occasional reactivity with VVA and CU-1, cells of normal colonic mucosa did not express Tn, sialosyl-Tn, or T antigens. However, in the transitional mucosa immediately adjacent to cancer, all three antigens were expressed (ranging from 35 to 67% of cases depending upon the reagent). In colon cancers, the percentage of cases expressing each antigen were as follows: Tn 72 81%, sialosyl-Tn 93-96%, and T 71%. Unlike T antigen, which was preferentially expressed by moderately well- and well-differentiated adenocarcinomas, both Tn and sialosyl-Tn antigens were expressed by most histological subsets of colon cancers, including poorly differentiated adenocarcinomas and mucinous (colloid and signet ring cell type) carcinomas. The majority of cancers expressed both Tn and sialosyl-Tn, usually in association with T antigen. Only one cancer lacked all three antigens. Fetal colonic mucosal cells expressed all three antigens, particularly in goblet cell mucin. These results indicate that like T antigen, Tn and sialosyl-Tn are oncodevelopmental cancer-associated antigens in the colon. Moreover, Tn and sialosyl-Tn antigens appear to be useful markers of poorly differentiated adenocarcinomas and mucinous carcinomas: two histological subsets that often fail to express other cancer-associated antigens and that are often associated with a poor clinical outcome.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2908847 TI - Mutagenicity and tumorigenicity of dihydrodiols, diol epoxides, and other derivatives of benzo(f)quinoline and benzo(h)quinoline. AB - The mutagenic activities of benzo[f]quinoline, benzo[h]quinoline, and a number of their derivatives, including dihydrodiols, K-region oxides, diol epoxides, and tetrahydroepoxides, were assessed in strain TA 100 of Salmonella typhimurium. The dihydrodiol derivatives of benzo[f]quinoline and benzo[h]quinoline were also tested for tumorigenic activity in newborn mice. Benzo[f]quinoline was metabolically activated in the presence of rat liver S-9 preparation to products mutagenic to the bacterial system to a greater extent than was benzo[h]quinoline. However, trans-7,8-dihydro-7,8-dihydroxybenzo[f]quinoline was less mutagenic compared to trans-7,8-dihydroxy-7,8-dihydrobenzo[h]quinoline in the presence of rat liver homogenate. The data on the mutagenic activity of the dihydrodiol derivatives of benzoquinolines were consistent with the intrinsic mutagenicity of the corresponding epoxide derivatives, in that the bay-region diol epoxides and tetrahydroepoxide of benzo[h]quinoline exhibited considerably higher mutagenic activities compared to those of the corresponding derivatives of benzo[f]quinoline at equivalent doses. The K-region oxides of benzo[f]quinoline and benzo[h]quinoline were significantly less mutagenic than their corresponding bay-region diol epoxide and tetrahydroepoxide derivatives. The demonstration that benzo[f]quinoline is significantly more mutagenic than trans-7,8-dihydro-7,8 dihydroxybenzo[f]quinoline, a precursor to the weakly mutagenic bay-region diol epoxide, suggests that the bay-region diol epoxide formation is not the principal pathway for the metabolic activation of benzo[f]quinoline to a mutagen. On the other hand, the isomeric benzo[h]quinoline appears to exert its mutagenic effect via the formation of its bay-region diol epoxide. These results indicate that the position of a nitrogen heteroatom in phenanthrene (the analogous carbocyclic aromatic hydrocarbon) not only has a marked effect on the mutagenic activities of the diol epoxide derivatives, but also can alter the metabolic activation pathways of the parent hydrocarbon. Benzo[f]quinoline, benzo[h]quinoline, and their dihydrodiol derivatives were not tumorigenic in newborn mice. PMID- 2908848 TI - Incidence of adult T-cell leukemia/lymphoma among human T-lymphotropic virus type I carriers in Saga, Japan. AB - Using a population-based cancer registry, we tabulated 69 definite adult T-cell leukemia/lymphoma cases (36 males and 33 females) and 2.20 expected cases (0.95 for males and 1.25 for females) diagnosed from 1981 to 1983 in Saga, Japan. The number of human T-lymphotropic virus type I carriers was computed by applying sex and age-specific anti-human T-lymphotropic virus type I antibody positive rates among blood donors at the blood center in 1986 to the whole population of Saga Prefecture in 1982. The age-specific incidence rates among male human T lymphotropic virus type I carriers from 40 to 79 yr of age per 100,000 were significantly higher than those of female carriers (P less than 0.05), and the rates from 60 to 69 yr of age were the highest in both sexes. The annual crude incidence rates among carriers were 115.9 for males and 66.4 for females. The summary incidence rates with 95% confidence intervals were 115.9 (58.4 to 193.0) for males and 65.9 (30.0 to 115.9) for females. The cumulative risks were 4.5% (0.8 to 11.0) for males and 2.6% (0.3 to 7.0) for females. These morbidity figures were assumed to be underestimated partly due to the newly proposed clinical entity of adult T-cell leukemia/lymphoma. PMID- 2908849 TI - Breast cancer after multiple chest fluoroscopies: second follow-up of Massachusetts women with tuberculosis. AB - A second follow-up was conducted of 1742 women with tuberculosis who were treated in one of two sanatoria in Massachusetts between 1930 and 1956. One hospital treated only children under the age of 17. Patient follow-up was extended from 1975 through 1980, and an additional 18 breast cancers were identified from hospital records, death certificates, and responses to a mailed questionnaire. Vital status was established for 97% of the subjects. Among 1044 women who were examined an average of 101 times with X-ray fluoroscopies during lung collapse therapy, 55 breast cancers were observed in contrast to 35.8 expected, based on incidence rates from the general population. No excess was found for 698 women treated by other means (19 observed versus 22.8 expected). Excess breast cancer risk did not appear until 15 years after initial exposure and was present at the end of 50 years of observation. Risk appeared to decrease with increasing age at exposure. Estimates of radiation dose to the breast for individuals (mean = 96 rad) were based on the most current information for the numbers of fluoroscopies, reconstruction of exposure conditions, and absorbed dose calculations. The relation between dose and breast cancer risk was consistent with linearity up to 400 rads (4 Gy). For 10-year survivors, the absolute excess risk was 5.5/1 million woman-year-rad, the excess relative risk per rad was 0.73%, and the relative risk at 100 rad was 1.7. These data indicate that a woman's lifetime risk of breast cancer is influenced by events occurring in early reproductive life, that low-dose fractionated exposures are as effective as single exposures of the same total dose in inducing breast cancer, and that risk of radiogenic breast cancer persists for many years, and perhaps for life. PMID- 2908850 TI - Pharmacology studies of 1-beta-D-arabinofuranosylcytosine in pediatric patients with leukemia and lymphoma after a biochemically optimal regimen of loading bolus plus continuous infusion of the drug. AB - In an attempt to maximize the therapeutic index and to overcome the large variations in 1-beta-D-arabinofuranosylcytosine (ara-C) plasma levels and host toxicities that have been documented with standard HDara-C regimens (3 g/m2 over 3 h every 12 h x 8 or x12 doses), pediatric patients with acute lymphocytic leukemia or lymphoma in relapse were treated with a regimen of loading bolus followed immediately by continuous infusion of ara-C. In addition, patients received a single dose of etoposide (VP-16, 1 g/m2) prior to the ara-C administration. In four patients, total body irradiation was administered as part of a bone marrow transplantation preparative regimen after the ara-C administration. The regimen was designed to attain and maintain plasma steady state concentrations (Css) of ara-C three to four times the Km2 value of ara-C, which was determined with purified deoxycytidine kinase from the patients' tumor cells prior to treatment. Eight patients age 0.75 to 16 years with relapsed acute lymphocytic leukemia (three patients) or lymphoma (five patients, one with bone marrow involvement), received a test dose of 3 g/m2 ara-C injected over 1 h, and the plasma kinetics were determined. The peak plasma ara-C concentration of ara-C ranged from 57 to 199 microM with an average concentration of 103 +/- 49 microM; the half-lives of distribution (t1/2, alpha) and elimination (t1/2, beta) averaged 17 +/- 7 min and 4.04 +/- 3.1 h, respectively. The mean area under the plasma concentration time curve from 0 to 12 h (AUC0----12 h) of ara-C averaged 386.8 +/- 328.0 microMh (mean, +/- SD, n = 8). The peak concentration of uracil arabinoside averaged 501 +/- 123 microM, and it was eliminated with a t1/2, el of 2.3 +/- 0.6 h. The patients then received an individualized loading bolus (mean = 0.5 g/m2) followed by a continuous infusion regimen of ara-C (mean = 130 mg/m2/h), to achieve a Css in the range of 20 to 35 microM. The obtained plasma Css were similar to the desired ones, averaging in variation 10.7% +/- 8.2%. The percentage of variation of correlation of the AUC following the loading bolus plus the continuous infusion from 12 to 72 h was only 12.4% (mean = 2158 microMh, n = 8), whereas the percentage of variation of correlation of the AUC after the test dose of ara-C in the same patients was 84.8%.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2908851 TI - Metabolic oxidation of the carcinogens 4-aminobiphenyl and 4,4'-methylene-bis(2 chloroaniline) by human hepatic microsomes and by purified rat hepatic cytochrome P-450 monooxygenases. AB - Metabolic N-oxidation and ring-oxidation of carcinogenic arylamines by hepatic cytochromes P-450 are generally regarded as critical activation and detoxification pathways, respectively. Two arylamines with known human exposure, 4-aminobiphenyl (ABP) and 4,4'-methylene-bis(2-chloroaniline) (MOCA), have been examined as substrates for 10 different purified rat hepatic cytochromes P-450 and for human liver microsomal preparations from 22 individuals. Metabolites were analyzed by high-performance liquid chromatography and flow scintillation techniques. As reported for certain other carcinogenic arylamines, the isosafrole inducible isozyme, P-450ISF-G, had the highest catalytic activity for ABP N oxidation (13.6 nmol/min/nmol P-450), but P-450BNF-B, P-450UT-A, P-450UT-F, and P 450PB-B also showed appreciable activity. Ring-oxidation of ABP occurred only to a minor extent. In contrast, N-oxidation of MOCA was preferentially catalyzed by the phenobarbital-inducible enzymes, P-450PB-B and P-450PB-D (9.0 and 6.6 nmol/min/nmol P-450, respectively). MOCA ring-oxidation and methylene carbon oxidation showed varied cytochrome P-450 selectivity and accounted for 14 to 79% of total oxidation products. There was a 44-fold variation in rates of ABP N oxidation in the 22 human liver microsomal preparations, while rates of N oxidation of MOCA varied only 8-fold. Ring/methylene carbon-oxidation of MOCA accounted for 6-19% of total oxidation products in the case of the human microsomal preparations, whereas ring-oxidation of ABP accounted for less than 7% of total oxidation. In addition, there was a strong correlation (R = 0.90) between rates of ABP N-oxidation and phenacetin O-deethylation, which is considered a human genetic polymorphism. Moreover, both the ABP N-oxidation and phenacetin O-deethylation activities of human liver microsomes showed a good correlation (R = 0.72) with the levels of cytochrome P-450 immunochemically related to rat P-450ISF-G. These data indicate that specific inducible and constitutive cytochromes P-450 are involved in the metabolic activation and detoxification of the carcinogens ABP and MOCA. Therefore, individual profiles of cytochromes P-450, affected by both environmental and genetic factors, may be significant determinants of individual susceptibility to arylamine carcinogenesis. PMID- 2908852 TI - Effects of serum, transforming growth factor type beta, or 12-O-tetradecanoyl phorbol-13-acetate on ionized cytosolic calcium concentration in normal and transformed human bronchial epithelial cells. AB - Fluctuations in ionized cytosolic calcium ([Ca2+]i) are considered important signals for induction of growth or differentiation in mammalian cells. The resting concentrations of [Ca2+]i in normal and adenovirus 12-SV40 hybrid virus transformed (BEAS-2B) human bronchial epithelial cells were 63 +/- 15 nM (SD) and 44 +/- 15 nM, respectively. Eight % calcium-free fetal bovine serum rapidly caused a significant increase in [Ca2+]i, while causing both cell types to undergo squamous differentiation. When treated with 8% calcium-free fetal bovine serum, a serum-sensitive subclone of BEAS-2B cells exhibited a higher elevation of [Ca2+]i than a serum-resistant (i.e., not stimulated to differentiate by serum) subclone. However, a serum component involved in the induction of squamous differentiation, transforming growth factor type beta, did not increase [Ca2+]i in either normal cells or BEAS-2B cells. 12-O-Tetradecanoyl-phorbol-13-acetate, an exogenous inducer of squamous differentiation and activator of protein kinase C, did not increase [Ca2+]i, but did attenuate serum-induced elevation of [Ca2+]i. These results suggest that while an increase in [Ca2+]i is associated with serum-induced squamous differentiation, a cytosolic ionized calcium signal is not required for the initiation of the squamous differentiation pathway induced by either transforming growth factor type beta or 12-O tetradecanoylphorbol-13-acetate. PMID- 2908853 TI - Anticancer drugs as inhibitors of two polymorphic cytochrome P450 enzymes, debrisoquin and mephenytoin hydroxylase, in human liver microsomes. AB - To identify potential substrates for the debrisoquin and mephenytoin hydroxylation polymorphisms, we performed in vitro inhibition studies with human liver microsomes and the respective prototype substrates in the absence and presence of several anticancer drugs. (+)-Bufuralol 1'-hydroxylation (as the prototype reaction for the debrisoquin polymorphism) was tested at 5 microM substrate concentration and in the presence of cyclophosphamide (0 to 200 microM), teniposide (0 to 100 microM), vinblastine (0 to 220 microM), etoposide (0 to 200 microM), flavone acetic acid (0 to 1000 microM), or ifosphamide (0 to 200 microM). (S)-Mephenytoin 4-hydroxylation was tested at 60 microM substrate concentration and in the presence of the same drugs as above; vincristine was also tested at 0 to 200 microM. Teniposide competitively inhibited the 4 hydroxylation of (S)-mephenytoin, with a Ki of 12 microM (Km of the reaction = 65 microM). Etoposide and flavone acetic acid were weaker inhibitors of this reaction. The only agent to inhibit bufuralol hydroxylation was vinblastine, which did so with a Ki of 90 microM (Km of the enzyme for the substrate = 12 microM). We conclude that teniposide and high concentrations of flavone acetic acid could spuriously alter mephenytoin phenotype determination in cancer patients, and that teniposide deserves further investigation as a possible substrate for the genetically regulated mephenytoin hydroxylase. PMID- 2908854 TI - Effects of homoharringtonine on protein glycosylation in human bladder carcinoma cell T-24. AB - Rates of [3H]glucosamine and mannose incorporation into glycoproteins and dolichol-linked oligosaccharides in exponentially growing T-24 bladder cancer cells were examined after exposure to homoharringtonine (HHT). Two-h treatment of HHT (10 ng/ml) reduced [3H]glucosamine and mannose incorporation into the glycoproteins to 61% and 32% of controls. Concomitantly, respective sugar incorporation into dolichol-linked oligosaccharides was elevated 29% and 30% above control. The maximal inhibition of glycoprotein biosynthesis and stimulation of the lipid-linked oligosaccharides occurred within 2 to 4 h after exposure to 50 ng/ml of the drug. Prolonged drug exposure (greater than 8 h) resulted in generalized suppression of glycoprotein biosynthesis and lipid-linked oligosaccharide formation. The kinetic study indicated that the time course on reduction of glycoprotein biosynthesis and accumulation of dolichol-linked oligosaccharides paralleled the decline in protein synthesis. Further, the inhibition of glycoprotein synthesis and stimulation of dolichol-linked oligosaccharides were reversible 4 h after drug withdrawal. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis autoradiographic analysis of the [3H]mannose-labeled glycoprotein revealed no pronounced difference between HHT treated and control cells. These data suggest that the inhibition of glycosylation results from combined decrease of acceptors for glycoprotein biosynthesis with a simultaneous accumulation of the dolichol-linked oligosaccharides. Collectively these data may account for many of the HHT-induced bioresponses. PMID- 2908856 TI - Immunoanalytical detection of O4-ethylthymine in liver DNA of individuals with or without malignant tumors. AB - The detection and quantitation of carcinogen-DNA adducts in human cells are the key parameters in the molecular dosimetry of human exposure to environmental carcinogens. For investigating the possible relevance of alkylating N-nitroso compounds as causative agents in human carcinogenesis, we have quantitated O4 ethyl-2'-deoxythymidine (O4-EtdThd) in human liver DNA obtained from 33 autopsy specimens, i.e., 13 cases with primary liver cancer (LC), 8 with cancers other than liver cancer (OC), and 12 with noncancerous diseases (NC). None of the cases analyzed had a history of known occupational exposure to ethylating agents. The detection limit for O4-EtdThd was 3 X 10(-8) as a O4-EtdThd/dThd molar ratio in DNA, which was attained by the combination of prefractionation of DNA hydrolysates (= 20 mg of DNA/sample) by high performance liquid chromatography and competitive radioimmunoassay using anti-(O4-EtdThd) monoclonal antibody ER 01. Except for one case in each group, O4-EtdThd [or, alternatively, (an) unidentified structural modification(s) of DNA recognized by monoclonal antibody ER-01] was detected at mean (+/- SD) O4-EtdThd/dThd molar ratios of 39.9 +/- 40.2 x 10(-8), 53.5 +/- 74.0 X 10(-8), and 11.7 +/- 6.5 X 10(-8), respectively, in LC, OC, and NC. The difference of the O4-EtdThd content in DNA between LC and NC, or between LC + OC and NC, was statistically significant at P less than 0.05. These results suggest that humans are exposed to ethylating agents in vivo and that a premutagenic DNA lesion (O4-EtdThd) eventually accumulates in DNA, possibly to a biologically significant extent. PMID- 2908855 TI - Molecular analysis of spontaneous hypoxanthine phosphoribosyltransferase mutations in thioguanine-resistant HL-60 human leukemia cells. AB - We have measured the forward mutation rate at the hypoxanthine phosphoribosyltransferase (HPRT) gene of the human promyelocytic leukemia cell line HL-60 and have determined the molecular spectrum of spontaneous HPRT mutations in 45 independent 6-thioguanine-resistant HL-60 sublines. Four fluctuation tests using a total of 132 replicate HL-60 cultures revealed a mean forward mutation rate of HL-60 cells to thioguanine resistance of 1.7-6 x 10( 7)/cell/generation. Blot hybridization analysis of the X-linked HPRT gene using a human HPRT complementary DNA probe revealed abnormalities in HPRT gene structure and/or HPRT mRNA expression in 24 of 45 (53%) independent thioguanine-resistant HL-60 sublines. Six different classes of mutation were identified. The most prevalent (47%; 21 of 45 mutations) consists of mutations that are not detected by blot hybridization analyses and that do not disrupt HPRT mRNA production. These results suggest that a comparatively low forward mutation rate may be found in malignant human cells that exhibit both karyotypic and molecular evidence of genomic instability and that several different molecular classes of mutation may contribute to thioguanine resistance in HL-60, and perhaps in other, malignant human cells. The forward mutation assay system we have developed using the X linked HPRT gene of HL-60 cells may be useful for analyses of the mutagenic potential and molecular spectrum of mutations produced by chemotherapeutic agents, suspected human mutagens and carcinogens, and phagocyte respiratory burst oxidants in human cells. PMID- 2908857 TI - Cyclic changes in fluorescence polarization of a membrane probe during the cell cycle of an erythroid precursor cell line. AB - The membrane lipid bilayer of the K562 cell line undergoes marked changes during cell cycling. These changes can be detected by measuring the fluorescence polarization of the rod-like hydrophobic probe 1,6-diphenyl-1,3,5-hexatriene. Single-cell measurements were performed by flow microfluorometry on synchronized K562 cells. The fluorescence polarization of the probe increased after cell division and was maximal during the S phase. Concomitant with the transition from S to G2 and M phase was a decrease in fluorescence polarization. The data are interpreted as reflecting a minimal membrane lipid fluidity during the S phase and a maximal fluidity during the G2/M-phase of the above erythroid precursor cell line. PMID- 2908858 TI - Novel functions and cellular interaction of human lymphoid stromal cells with lymphoid cell lines in vitro. AB - Lymphoid stromal (SG) cells have been isolated from the lymph node of a patient with malignant lymphoma, and characterized by positive reaction with a monoclonal antibody against the T-zone stromal cells in human lymph nodes. B-acute lymphoblastic leukemia (BALL) cells showed prominent emperipolesis toward SG cells when they were cocultured, whereas T-acute lymphoblastic leukemia (TALL) cells attached firmly to the surface of SG cells. Autologous peripheral B and T cells behaved, respectively, in the same way as BALL and TALL cells. Both BALL and TALL cells while directly interacting with the SG cells were completely inhibited from incorporating [3H]thymidine, although radioactive grains were observed in 16.4%-12.4% of supernatant BALL and 13.8%-13.0% of supernatant TALL cells in each coculture. Furthermore the media conditioned by SG cells significantly increased the incorporation of [3H]thymidine into the TALL cells as much as 190% of the control. These results indicate that SG cells undergo tissue specific cellular interactions with B- and T-lymphoid cell lines but not with a myeloid cell line, and they can modify their growth by two distinct mechanisms. SG cells proved to be very useful in studying the effect of the lymphoid microenvironment on the proliferation of lymphocytes in vivo. PMID- 2908859 TI - Age-related variations of fat tissue fraction in normal human bone marrow depend both on size and number of adipocytes: a stereological study. AB - Studies dealing with the number or size of individual adipose cells in human bone marrow are lacking. To ascertain whether the age-related variations in fat tissue fraction depend on the size of individual adipocytes or their number or both, a stereological study of 20 normal human bone marrow specimens was performed. A total number of 17,039 adipose cell profiles was measured and two stereological parameters were obtained in each specimen: mean diameter and number of cells per mm3 of bone marrow. With increasing age, an increasing fat tissue fraction was observed (r = 0.61; p = 0.004). The fat tissue fraction correlated positively with the size (r = 0.81; p less than 0.001) and the number/volume (r = 0.59; p = 0.006) of adipocytes. The significance of both adipocyte size and adipocyte number/volume was confirmed by stepwise multiple regression, in which the size alone explained 66.2% of fat tissue fraction and both size and number/volume explained 97.2% of fat tissue fraction. These results are discussed from a pathophysiological point of view. PMID- 2908860 TI - Characteristics of megakaryocyte colony formation in normal individuals and in primary thrombocythemia: studies using an optimal cloning system. AB - Colony formation by megakaryocyte (MK) progenitors was studied in 36 normal individuals and in 26 patients with primary thrombocythemia (PT) using an improved plasma clot cloning system. MK colonies were identified by immunoperoxidase staining using a monoclonal antibody against human platelet glycoprotein IIb/IIIa complex. In normal individuals, a frequency of 194 +/- 23 MK colony-forming units (CFU-MK) per 5 X 10(5) bone marrow nonadherent mononuclear cells and 11 +/- 4 CFU-MK per 5 X 10(5) blood mononuclear cells was found. These CFU-MK grew as large (greater than 20 cells), mean (11-20 cells), small (3-10 cells), or mix-MK colonies (at least two MK) that comprised 15%, 23%, 62%, or 5% of all MK colonies in bone marrow and 0%, 8%, 92%, or 1% in peripheral blood, respectively. In PT, several abnormalities of MK colony formation were observed: 1) increased circulating CFU-MK numbers, 2) increased mix-MK colony formation, 3) spontaneous MK colony formation without phytohemagglutinin stimulated leukocyte-conditioned medium and normal serum, 4) decreased proportion of larger MK colonies (greater than 11 cells) in PT bone marrow, and 5) failure of PT plasma or serum to stimulate MK colony formation by normal marrow cells in a normal fashion. These results indicate some of the characteristics of quantitative and qualitative abnormalities of in vitro megakaryocytopoiesis in PT. PMID- 2908861 TI - Thymidine suicide and hydroxyurea kill ratios accurately reflect the proliferative status of stem cells (CFU-S). AB - We have previously found that on average 30% of hematopoietic stem cells (CFU-S) are in the S phase, which is at least three times the value published by others. Therefore, it seemed desirable to investigate the reliability of the methods used to measure the percentage of CFU-S in S phase. Various modifications of the [3H]thymidine suicide were tested and it could be demonstrated that results were not affected by them. Furthermore, results obtained with the [3H]thymidine suicide were compared to those obtained with methods utilizing hydroxyurea to kill CFU-S in S phase. The [3H]thymidine- and hydroxyurea-based methods gave parallel results. The parallel behavior validated all of these methods as reliable indicators of the turnover of CFU-S and presumably other stem cell populations. PMID- 2908862 TI - Antiproliferative effects of lipoxygenase inhibitors on malignant human hematopoietic cell lines. AB - Eicosanoids regulate a wide spectrum of cellular processes including cell proliferation. We have shown previously that lipoxygenase metabolites of arachidonic acid modulate normal human hematopoiesis by in vitro colony assays. In this study we investigated the role of lipoxygenase metabolites in regulating the proliferation of several malignant hematopoietic cell lines, including K562 and EM-2 (chronic myelogenous leukemia blasts), HL-60 (promyelocytic leukemia cells), and U937 (malignant histiocytes). Piriprost, a specific inhibitor of 5 lipoxygenase, inhibits proliferation of these cell lines up to 95% with 50% cell inhibition at approximately 3 x 10(-5) M. Other less specific lipoxygenase inhibitors such as caffeic acid, nordihydroguaiaretic acid, and BW755C have similar activity in a [3H]-thymidine incorporation assay. In contrast, indomethacin, which is a cyclooxygenase inhibitor, has no suppressive effect in these assays. Inhibition by these drugs is completely reversible. Several nonhematopoietic malignant cell lines do not appear to be affected by these drugs. Two specific lipoxygenase metabolites, leukotriene B4 and leukotriene D4, stimulate leukemia cell line proliferation to 150% of control levels when added directly to cell cultures. These data suggest that certain lipoxygenase products, perhaps leukotrienes, are critical for the proliferation of malignant hematopoietic cells in vitro. PMID- 2908863 TI - Decline in cycling of granulocyte-macrophage colony-forming cells with increasing age in mice. AB - The cycling state of granulocyte-macrophage progenitor cells (GM-CFC) was measured using the [3H]thymidine suicide technique in individual male B6D2F1 mice. The proportion of the GM-CFC population in S phase was found to decrease from 25%-35% at 1-6 months of age to about 10% in mice greater than 2 years old. PMID- 2908864 TI - Metoprolol-induced hepatitis: is the rate of oxidation related to drug-induced hepatotoxicity? PMID- 2908865 TI - Treatment of post-shunt portal systemic encephalopathy by embolization of the shunt. AB - Operative ligation of portosystemic shunts is effective in controlling chronic portosystemic encephalopathy (CPSE) but is associated with significant mortality. Review of the records of five patients with CPSE treated with radiologic occlusion procedures showed that these are suitable alternatives to surgery. Three patients had alcoholic cirrhosis, one had hepatic fibrosis from schistosomiasis, and one had post-necrotic cirrhosis. All had CPSE with progressive, severe cerebral impairment refractory to clinical treatment. Four patients had a spontaneous splenorenal shunt, and one had a surgically created mesocaval shunt (MCS). Partial splenic embolization was performed in two patients, direct shunt embolization was performed via percutaneous transhepatic portography in two other patients, and an MCS embolization was performed in one patient through the inferior vena cava. In four patients embolization controlled the CPSE. In the remaining patient it could not be evaluated because of his premature death from intraabdominal bleeding, a late complication of the procedure. Interventional radiologic procedures are effective in the control of CPSE in selected patients. PMID- 2908866 TI - Primary lymphoma of the liver: a more optimistic point of view. PMID- 2908867 TI - Differential location of hemopoietic colonies within liver acini of postnatal and phenylhydrazine-treated adult mice. AB - We have measured the location of embryonic and adult hemopoietic foci in the liver tissue of postnatal and adult phenylhydrazine-treated mice. Differentiation of acinar domains in liver tissue was made possible by carrying out succinate dehydrogenase histochemical reactions on liver cryostat sections. To determine the position of hemopoietic foci within the lobular gradient of the hepatocyte succinate dehydrogenase activity, this enzyme was measured in hepatocytes surrounding both portal and central veins and hemopoietic foci. Then, assuming the periportal succinate dehydrogenase activity value to be 1.00 +/- 0.2, succinate dehydrogenase activity around postnatal hemopoietic foci was 0.65 +/- 0.19, around phenylhydrazine-induced hemopoietic foci 0.83 +/- 0.24 and around central veins 0.44 +/- 0.11. Scaling the portal to central vein distance and taking 1 as the portal vein point and 0 as the central vein point, the relative position of hemopoietic foci, indirectly calculated from succinate dehydrogenase activity values, was 0.35 +/- 0.13 in postnatal livers and 0.73 +/- 0.12 in phenylhydrazine-treated adult livers. Hemopoietic foci frequencies varied according to both the origin and the liver acinar domain: in postnatal liver acini, it was 37.1% in zone 1, 22.8% in zone 2 and 40% in zone 3; in phenylhydrazine-treated adult acini, it was 89.4% in zone 1 and 10.6% in zone 2. Postnatal hemopoietic foci mainly occurred extrasinusoidally, between hepatocytes and reticular-like cells, whereas adult hemopoietic foci were mostly intrasinusoidal and closely associated to macrophage-like cells. Adult hemopoietic colonies PMID- 2908868 TI - Proline-incorporating cells in chronic active liver diseases. AB - The incorporation of 3H-proline in cells of liver biopsy specimens from patients with chronic active liver diseases has been studied by light and electron microscopic autoradiography. The labeled proline is incorporated by hepatocytes of the external rows of the residual liver lobule, by the cells of the proliferating bile ductule and very actively by the plasma cells localized at the boundary between the inflammatory infiltrate and the liver lobule. These plasma cells, which are often in close contact with the hepatocytes at the edge of the liver lobule, appear to be either negative or positive after the immunohistochemical tests for the k and lambda chains of immunoglobulins. Results are discussed in relation to both the synthesis of collagen and the role of the immunocompetent cells during the process of the piecemeal necrosis. PMID- 2908869 TI - Preferential covalent binding of acetaldehyde to the alpha-chain of purified rat liver tubulin. AB - Hepatic ethanol oxidation generates the reactive intermediate acetaldehyde, which binds to proteins. Previous work, using bovine brain tubulin as a model protein, has shown that acetaldehyde preferentially formed stable adducts on the alpha chain of the heterodimeric molecule. This binding resulted in functional impairment of the tubulin/microtubule system as evidenced by a decreased ability of adducted tubulin to form microtubules. Since tubulin/microtubules are believed to be very important cytoskeletal components of the hepatocyte and results with brain tubulin were interesting, our goal was to extend these studies to liver tubulin. We purified tubulin from rat liver by a polymerization-based cycle method followed by phosphocellulose chromatography. We then characterized the covalent binding of [14C]acetaldehyde to liver tubulin. Naturally forming and cyanoborohydride-stimulated stable adducts formed linearly with liver tubulin in a manner almost identical to that with brain tubulin. We also found that the alpha-chain of the native heterodimeric liver tubulin molecule was the preferred site of adduct formation at low acetaldehyde to protein ratios. These results confirm and extend our previous findings with the brain tubulin model and further suggest that the alpha-chain of tubulin may be a preferential site for acetaldehyde-adduct formation during ethanol oxidation in the liver. PMID- 2908870 TI - Reactivity of primary biliary cirrhosis sera with a human fetal liver cDNA clone of branched-chain alpha-keto acid dehydrogenase dihydrolipoamide acyltransferase, the 52 kD mitochondrial autoantigen. AB - Antimitochondrial autoantibodies recognizing 68 to 74 and 50 to 52 kD inner membrane mitochondrial antigens are characteristically present in sera of patients with primary biliary cirrhosis. The biochemical identification of the antigens, however, has remained elusive. We report herein that the 52 kD antigen is the dihydrolipoamide acyltransferase of the branched-chain alpha-keto acid dehydrogenase complex. This was demonstrated by three experiments through the use of recombinant fusion protein expressed in Escherichia coli from a cDNA insert encoding the human autoantigen. First, 33 of 37 primary biliary cirrhosis patients exhibiting reactivity toward the 50 to 52 kD mitochondrial antigen by immunoblotting also showed reactivity toward the recombinant fusion protein. Second, absorption of primary biliary cirrhosis sera with recombinant fusion protein, but not with an irrelevant recombinant clone, the F-specific rat liver antigen, was effective in absorbing out reactivity against the 50 to 52 kD mitochondrial antigen but not the 68 to 74 kD antigen. Third, complete removal of reactivity toward all four different isoelectric point polypeptides at 50 to 52 kD was observed in two-dimensional gel analysis. Furthermore, primary biliary cirrhosis sera were analyzed with mitochondria from three sources, rat liver, human placenta and bovine heart, in order to compare reactivity patterns and to determine precisely the comparative molecular weights of the autoantigens in the three species. The availability of recombinant autoantigens will provide improved diagnostic tests and, more importantly, will allow definite issues in primary biliary cirrhosis to be studied, including identification of immunodominant epitopes, the significance of autoantigen recognition and the establishment of autoreactive T cell clones. PMID- 2908871 TI - A simplified single stage total hepatectomy in the rat with maintenance of gastrointestinal absorptive function. AB - A technique is described to remove the entire liver in a single stage with preservation of intestinal absorptive function. An inverted V-shape polyethylene cannula, either heparin bonded or silicon coated, was inserted into the portal vein and inferior vena cava to maintain venous return from the splanchnic and lower caval regions of the anhepatic rat. Blood glucose fell at a rate of 7 to 11 mg per hr per total plasma volume (4% body weight), usually resulting in hypoglycemia within the initial 2 hr. Euglycemia could be maintained in the first 3 hr after hepatectomy with hourly intravenous infusions of 2.5 to 5 mg per 100 gm body weight of glucose. Larger infusions of glucose (10 to 12.5 mg per hr per 100 gm body weight) were necessary for normal levels at later times. A 0.5 gm per 100 gm rat weight intestinal glucose bolus restored euglycemia for at least a 2 hr interval. Intestinal absorption of cholesterol and oleic acid was demonstrated in the anhepatic rat, although the latter was not so efficiently absorbed as in the control. The plasma cholesterol decreased with time in the anhepatic rat. Prompt increases were observed in plasma free fatty acid and glycerol concentrations after hepatectomy. Progressive increases in both direct and indirect plasma bilirubin levels were noted after hepatectomy. With appropriate maintenance of blood sugar, survival of 36 hr was observed. This procedure for single stage total hepatectomy in the rat can be performed in less than 30 min. The model is particularly useful for studies of the influence of the liver on postabsorptive metabolism. PMID- 2908872 TI - Combination of ketanserin and verapamil or propranolol in patients with alcoholic cirrhosis: search for an additive effect. AB - Drugs reported to reduce portal pressure through different mechanisms were combined in the hope of either additive portal hypotensive effects in "responders," or inducing a portal hypotensive effect in "nonresponders" to the initial drug. Seven patients with alcoholic cirrhosis received verapamil, 10 mg i.v., and, 60 min later, ketanserin, 5 mg i.v. Verapamil decreased heart rate and increased free hepatic venous pressure but had no effect on hepatic venous pressure gradient or azygos blood flow. When combined with verapamil, ketanserin significantly diminished wedged hepatic venous pressure and hepatic venous pressure gradient. Ten other patients with alcoholic cirrhosis received propranolol, 15 mg i.v., and 45 min later, ketanserin, 5 mg i.v. In all patients, heart rate, cardiac index and azygos blood flow significantly decreased after propranolol. After propranolol alone, however, wedged hepatic venous pressure decreased in only five patients, responders. In five other patients, defined as nonresponders, propranolol did not decrease this pressure. The addition of ketanserin to propranolol induced further significant reduction in wedged hepatic venous pressure, hepatic venous pressure gradient and azygos blood flow. Among the five nonresponders, three had a reduced wedged hepatic venous pressure after ketanserin was combined. We conclude that verapamil does not reduce portal pressure or collateral blood flow in patients with alcoholic cirrhosis. The splanchnic hemodynamic effects of propranolol and ketanserin appear to be independent and additive, without significant systemic alteration. PMID- 2908873 TI - Long-term hemodynamic effects of ketanserin, a 5-hydroxytryptamine blocker, in portal hypertensive patients. AB - Ketanserin, a 5-hydroxytryptamine-2 receptor blocker, has been shown to decrease portal pressure in recent acute hemodynamic studies that have been performed both in experimental animals and portal hypertensive patients. The present study was designed to investigate the effects of chronic oral administration of ketanserin in portal hypertensive patients with cirrhosis. The mean baseline hepatic venous pressure gradient in the 13 patients with alcoholic cirrhosis who completed the study was 15.7 +/- 2.7 mmHg. It decreased significantly to 13.3 +/- 2.0 mmHg (p less than 0.001) after ketanserin was administered at a mean dose of 51 mg per day for a mean period of 32 days. This 14.6% reduction in hepatic venous pressure gradient resulted mainly from a decrease in mean wedged hepatic venous pressure (from 22.2 +/- 4.0 to 20.1 +/- 3.6 mmHg) and was accompanied by significant decreases in cardiac index (18.8%) and in mean arterial pressure (8.1%). However, changes in cardiac index or in mean arterial pressure were not predictive of modifications in the hepatic venous pressure gradient. Eight of 16 patients entered in the study developed side effects, the most significant being a reversible portosystemic encephalopathy, which occurred in three patients who had poor liver function. This study confirms evidence in favor of a role for 5 hydroxytryptamine in portal hypertension and adds a new group of agents for the chronic treatment of portal hypertensive patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2908874 TI - Analysis of the HLA-A10-crossreacting group of antigens by one-dimensional isoelectric focusing. AB - The antigens belonging to the HLA-A10 group, HLA-A25, -A26, -Aw34, and -Aw66, have been characterized serologically during the International Histocompatibility Workshops. However, it remains difficult to discriminate between the HLA-A26 antigen on the one hand and the HLA-Aw34 and -Aw66 antigens on the other on the basis of serology. In this paper, we compare the serologically defined antigens with the data obtained by one-dimensional isoelectric focusing. The results indicate that the serologically well-defined HLA-A25 antigen cannot be discriminated from the HLA-A26 antigen by one-dimensional isoelectric focusing. In contrast, this technique can indeed be used to discriminate between HLA-A26, Aw34 and -Aw66 antigens. In addition, the biochemical analysis suggests further heterogeneity of the HLA-Aw34 antigen. This antigen can be subdivided into three variants. PMID- 2908875 TI - A novel H-2K splice form: predictions for other alternative H-2 splicing events. AB - A large number of H-2K and H-2D cDNA clones from a C3HfB/HeN spleen cDNA library were extensively characterized. All H-2Dk cDNAs were shown to exhibit the short form of exon 8, consistent with the presence of a single lariat branchpoint site within intron 7. Twenty-five H-2Kkm2 cDNAs were found to bear a short exon 8, whereas only two clones were shown to carry the longer form of this exon. In one of the H-2Kkm2 cDNAs, a novel pattern of H-2 splicing was identified, in which an extra 15 nucleotides, derived from the 3' end of intron 5, were inserted between the intact and unaltered exon 5 and exon 6 sequences. Resulting from the apparent use of a cryptic splice acceptor site in place of the canonical intron 5 site, this insertion is predicted to generate an in-frame insertion of five nonpolar amino acid residues within a highly polar region of the intracytoplasmic domain of the H-2K polypeptide. The features of this novel splice form served as the basis for predicting additional rare, alternative H-2 pre-mRNA splicing events that might produce functionally relevant microheterogeneity in the encoded H-2 gene products. PMID- 2908876 TI - Twenty-six DR beta and 16 DQ beta chain IEF variants and their associated HLA-DR, HLA-DQ, and HLA-Dw specificities. PMID- 2908877 TI - The mouse mutation severe combined immune deficiency (scid) is on chromosome 16. PMID- 2908878 TI - Cloning and characterization of a BoLA class I cDNA clone. PMID- 2908879 TI - Regulation of expression of mouse C4 and Slp genes by non-H-2-linked genes. AB - C4 (the fourth complement component) and Slp (sexlimited protein) are two homologous plasma proteins encoded by genes in the S-region of the H-2 gene complex. We studied the genetic factors influencing the plasma levels of these proteins and their mRNA levels in liver. Considerable differences in both protein and mRNA levels were found between mouse strains carrying the same S-region allele on different genetic backgrounds, indicating a pretranslational effect of non-H-2-linked genes on the expression of the two S-region genes. The expression of Slp is androgen-dependent in the strains tested. However, testosterone treatment cannot increase the low levels of Slp caused by non-H-2-linked regulatory genes. In mice with Slp-negative S-region alleles we found liver mRNA hybridizing with Slp-specific oligonucleotides, indicating expression of the Slp gene in Slp-negative strains. Our data demonstrate the complexity of the regulation of the C4 and Slp genes and pave the way for the analysis of the regulatory factors involved. PMID- 2908880 TI - DNA repair, sensitivity to gamma radiation and to heat shock in lymphocytes from acute, untreated multiple sclerosis patients. AB - Increases in spontaneous sister chromatid exchange (SCE) and gamma radiation induced chromosome aberrations have been reported in peripheral blood lymphocytes (PBL) from multiple sclerosis (MS) patients, suggesting the presence of an abnormality in repair in this disease. We tested this hypothesis by measuring the ability to repair DNA and survival, after exposure to low (2-12 Gy) and high (100 Gy) gamma ray doses or to a high temperature (37-45 degrees C), of freshly isolated PBL from 15 patients affected by definite MS and 15 healthy subjects. The MS patients were untreated and in the acute phase of the disease. No significant difference was found between the two groups. We suggest that the previously reported genomic instability may be of viral origin and not due to a genetic defect in repair of DNA in these patients. PMID- 2908881 TI - Alpha-bungarotoxin blocking antibodies in neonatal myasthenia gravis: frequency and selectivity. AB - We have studied antibodies to the acetylcholine receptor (AChR) that inhibit alpha-bungarotoxin binding in 22 mothers with myasthenia gravis (MG) and in their 23 newborns. Of the 13 showing neonatal MG, seven of the mothers had detectable direct blocking antibodies, all 13 had decamethonium-dependent (DC) blocking, and nine had high titres of precipitating antibodies (greater than 40 nM). In those with symptom-free newborns, the corresponding figures were 2/10, 8/10 and 2/10; the mean titres of DC blocking and of precipitating antibodies were 5- and 3-fold lower than in the mothers of affected babies. Thus, blocking antibodies, in addition to high total antibody levels, may help to predict the occurrence of neonatal MG. However, the antibodies appear not to cross the placenta to the same extent in each case. 86, 69 and 84% of the maternal antibodies with precipitating, direct and DC blocking activities, respectively, were found in the myasthenic neonates versus 65, 28 and 44% in the unaffected. These data suggest (1) involvement of blocking antibodies in the pathogenesis of MG, and (2) variable placental transfer of anti-AChR antibodies, which makes neonatal affliction more difficult to predict. PMID- 2908882 TI - Canine distemper virus infectivity of various blood fractions for central nervous system vasculature. AB - In order to determine the infectivity of various viremic blood fractions for central nervous system (CNS) endothelia, viremic plasma, platelets and mononuclear cells were prepared from canine distemper virus (CDV)-infected dogs and infused into the right carotid arteries of CDV-naive gnotobiotic dogs. All blood fractions were infectious for endothelia as determined by indirect immunofluorescence examination for viral antigen in recipients. Virus-positive platelets, even though possessing only trace amounts (1.0 x 10(1) TCID50/ml) of in vitro titratable virus, were the most effective fraction for infection of vascular endothelium. These data confirm the important role of vascular endothelia in establishing CNS infection in this disease and implicate virus positive platelets and leukocytes in the initiation of this phenomenon. PMID- 2908883 TI - Internalization of horseradish peroxidase isozymes by pancreatic acinar cells in vitro. AB - We examined the uptake and fate of four horseradish peroxidase (HRP) isozymes (Type VI, VII, VIII, and IX) in isolated pancreatic acinar cells. The pattern of uptake was similar for all the isozymes examined, with the exception of Type IX. Very little Type IX HRP was internalized by the cells, and what endocytosis did occur was primarily from the apical cell surface in coated vesicles. In contrast, HRP Type VI, VII, and VIII appeared to be endocytosed largely at the basolateral cell surface. Initially, the tracer was found in smooth vesicles and tubules near the plasma membrane. The tubules resembled the basal lysosomes known to be present in these cells. At the early time points, HRP reaction product was also present in multivesicular bodies (MVBs). By 60 min, the HRP was localized in MVBs, vesicles, and tubules adjacent to the Golgi apparatus. By 12 hr after exposure to the isozymes, the tracer was present in small apical vesicles. At no time could reaction product be localized in the rough endoplasmic reticulum, Golgi saccules, or secretory granules. The results of this study suggest that the charge of a soluble-phase marker has little effect on its uptake or intracellular distribution. PMID- 2908884 TI - A minibead method for detection of membrane lectins. AB - Membrane lectins are being increasingly implicated in many biological phenomena. Previous methods for detection of these substances are applicable only to homogeneous cell populations. We have now developed a method that permits morphological identification of lectin-bearing cells in heterogeneous cell populations. Amide-modified latex minibeads (0.345 or 0.532 micron) were activated with glutaraldehyde and then covalently bound to p-aminophenyl derivatives of various sugars. When the probe thus constructed was incubated with cell systems known to bear well-defined membrane lectins (galactosyl receptors in hepatocytes, mannosyl receptors in macrophages), binding occurred and could be visualized by scanning electron microscopy. Binding was inhibited in the presence of excess soluble sugar, indicating the specificity of reaction. Incubation of a mixture of two different-sized probes with two different cell types led to segregation of the probes. This method also permits semiquantification of binding. PMID- 2908885 TI - Direct adrenal medullary catecholamine response to hypoxia in fetal sheep. AB - The present study was designed to investigate the direct response of fetal adrenomedullary cells to hypoxia, and the possible change in this responsiveness with maturation. Ovine fetal adrenomedullary cells, when exposed to 30 min of hypoxia induced by perfusing with Krebs-Henseleit solution equilibrated with 1% O2, released significantly greater amounts of total catecholamine into the perfusate, compared to basal conditions. After a 1-h control period, a second 30 min hypoxic episode stimulated a catecholamine response which was significantly smaller in magnitude than the first. Following the two hypoxic episodes, the cells were capable of responding to 50 mM KCl with a large increase in total catecholamine release. During the first hypoxic episode, the release of both norepinephrine and epinephrine was stimulated by equal magnitude. Fetal adrenomedullary cells obtained from fetuses at 100, 120, and 130 days gestation showed similar responsiveness to the same hypoxic stimulus, and these responses were not different from that observed in maternal adrenomedullary cells. On the contrary, responsiveness to KCl-induced depolarization was greatest in cells obtained from fetuses at 130 days gestation when compared to that in the younger fetuses. This increased responsiveness to KCl was accompanied by a greater catecholamine store in the adrenal medulla of the fetuses at this gestational age. These results suggest that ovine fetal adrenomedullary cells can respond directly to hypoxia by releasing catecholamines. This direct responsiveness became desensitized after repeated exposure. Finally, a decrease in direct responsiveness to hypoxia associated with maturation could be demonstrated. PMID- 2908886 TI - Effects of lactic acidosis on the function of cerebral cortical synaptosomes. AB - Synaptosomes exposed to anoxic insult produce lactate at a slow rate (measured over 60 min). No measurable damaging effects were produced by prolonged depolarisation, anoxic insult, or exogenous lactate (2-32 mM) either on the synaptic plasma membrane (as judged by release of lactate dehydrogenase and soluble proteins), or on synaptosomal phospholipases (as judged by choline release from membrane phospholipids). Potassium-stimulated acetylcholine release was decreased by incubation in the presence of lactate (2-32 mM), as was potassium- and veratrine-stimulated calcium uptake and the calcium content of depolarised synaptosomes. The intrasynaptosomal pH was also reduced but there was no stimulation of oxygen radical production (as judged by H2O2 generation) by exogenous lactate. The role that lactic acidosis may play in giving rise to the altered calcium homeostasis and decreased acetylcholine release from synaptosomes exposed to anoxic insult is discussed. PMID- 2908887 TI - Developmental expression of the glial fibrillary acidic protein mRNA in the central nervous system and in cultured astrocytes. AB - The expression of glial fibrillary acidic protein (GFAP)-mRNA during mouse brain development and in astroglial primary cultures has been investigated by using two approaches: Northern-blot evaluation using a specific cDNA probe, and cell-free translation associated with immunoprecipitation. During brain maturation (4-56 days postnatal), the GFAP-mRNA underwent a biphasic evolution. An increase was observed between birth and day 15 (i.e., during the period of astroglial proliferation), which was followed by a decrease until day 56 (i.e., during astroglial cell differentiation). At older stages (300 days), an increase was observed, which might reflect gliosis. During astroglial in vitro development (7 32 days in culture), the GFAP-mRNA showed similar variations. An increase, observed during the period of astroglial proliferation (7-18 days), was followed by a decrease which occurred in parallel to marked changes in cell shape, cell process outgrowth, and the organization and accumulation of gliofilaments. During the same culture period (7-32 days), alpha-tubulin mRNA, which was used as an internal standard, did not vary significantly. These results show that the increase of the GFAP protein and of gliofilaments observed both in vivo and in vitro during astroglial differentiation cannot be ascribed to an accumulation of the GFAP-mRNA. It might be that more than one mechanism regulates the levels of free and polymerized GFAP and of its encoding mRNA. PMID- 2908888 TI - Modulation of ganglioside biosynthesis in primary cultured neurons. AB - Murine cerebellar cells were pulse labeled with [14C]galactose, and the incorporation of radioactivity into gangliosides and neutral glycosphingolipids was examined under different experimental conditions. In the presence of drugs affecting intracellular membrane flow, as well as at 15 degrees C, labeled GlcCer was found to accumulate in the cells, whereas the labeling of higher glycosphingolipids and gangliosides was reduced. Monensin and modulators of the cytoskeleton effectively blocked biosynthesis of the complex gangliosides GM1, GD1a, GD1b, GT1b, and GQ1b, whereas incorporation of radioactivity into neutral glycosphingolipids, such as glucosylceramide and lactosylceramide, as well as GM3, GM2, and GD3 was either increased or unaltered. As monensin has been reported to interfere with the flow of molecules from the cis to the trans stacks of the Golgi apparatus, this result highlights at least one subcompartmentalization of ganglioside biosynthesis within the Golgi system. Inhibitors of energy metabolism affected, predominantly, the biosynthesis of the b-series gangliosides, whereas a reduced temperature (15 degrees C) more effectively blocked incorporation of radiolabel into the a-series gangliosides, a result suggesting the importance of GM3, as the principal branching point, for the regulation of ganglioside biosynthesis. PMID- 2908889 TI - Rat brain protein kinase C: purification, antibody production, and quantification in discrete regions of hippocampus. AB - Protein kinase C (PKC), a calcium- and phospholipid-dependent kinase, is highly enriched in rat brain, where it may function in signal transduction processes. We purified rat brain PKC to homogeneity by a three-column procedure of diethylaminoethyl-cellulose, phenyl-Sepharose, and protamine-agarose with a yield of 16% and a final specific activity of 9,600 pmol of [3H]phorbol-12,13 dibutyrate bound/mg of protein. The pure protein consisted of a doublet of 80 and 78 kilodaltons. Rabbit antibodies prepared against a beta-type PKC synthetic peptide sequence (RAKIGQGTKAPEEKTANTISK) showed high specificity and sensitivity for PKC and recognized only the 78-kilodalton form of PKC. Micropunches (300 microns in diameter) of rat hippocampal subregions were solubilized in sodium dodecyl sulfate (SDS) sample buffer, electrophoresed on SDS-10% polyacrylamide gels, and transferred to nitrocellulose. PKC was visualized by 125I-protein A autoradiography and quantified by densitometry. The highest concentrations of PKC were found in the CA1 pyramidal cell layer (0.43 +/- 0.04 OD), with the lowest amounts in the CA3 and CA4 pyramidal cell layers (0.11 +/- 0.02 and 0.085 +/- 0.006 OD, respectively). These results demonstrate a simple way of preparing antibodies against domains of PKC. We also describe a procedure for quantifying the relative amounts of PKC in discrete brain regions. PMID- 2908890 TI - Molecular characterization of an ependymin precursor from goldfish brain. AB - Ependymins are thought to be implicated in fundamental processes involved in plasticity of the goldfish CNS. Gas-phase sequencing of purified ependymins beta and gamma revealed that they share the same N-terminal sequence. Each sequence displays microheterogeneities at several positions. Based on the protein sequences obtained, we constructed synthetic oligonucleotides and used them as hybridization probes for screening cDNA libraries of goldfish brain. In this article we describe the full-length sequence of a mRNA encoding a precursor of ependymins. A cleavable signal sequence characteristic of secretory proteins is located at the N-terminal end, followed directly by the ependymin sequence. Also, two potential N-glycosylation sites were detected. A computer search revealed that ependymins form a novel family of unique proteins. PMID- 2908891 TI - Translational regulation of myelin protein synthesis by steroids. AB - Various steroids, including glucocorticoids, were observed to exert a direct effect on the rates of translation of several myelin-protein specific transcripts in a cell-free, reticulocyte lysate system. Hydrocortisone caused a twofold stimulation in the translation of mRNAs of myelin basic protein and proteolipid protein. It inhibited the translation of 2',3'-cyclic nucleotide 3' phosphodiesterase mRNA by 50%, and had no effect on the translation of a number of other mRNAs. The data suggest that steroid-mediated translational regulation may serve as a novel mechanism to modulate the expression of myelin protein genes at the translational level. PMID- 2908892 TI - Mitogenic effect of axolemma-enriched fraction on cultured oligodendrocytes. AB - An in vitro system has been devised to study the mitogenic effect of axolemma on cultured oligodendrocytes. Addition of axolemma-enriched fraction to cultured oligodendrocytes results in a dose-dependent mitotic response with an 11-fold stimulation at a membrane concentration of 200 micrograms/ml. The interaction between oligodendrocytes and axolemma is specific, as myelin-enriched fraction, astrocyte membrane, and red blood cell membrane showed little or no effect on the oligodendroglial proliferation under similar conditions. In addition, cultured astrocytes were tested with the same axolemma membrane, and no mitotic stimulation was observed. The mitogenicity of AEF membrane on cultured oligodendrocytes is sensitive to heat and trypsin treatment, suggesting that the axolemma mitogen may be a protein. PMID- 2908893 TI - Purified rat brain myelin contains measurable acyl-CoA:lysophospholipid acyltransferase(s) but little, if any, glycerol-3-phosphate acyltransferase. AB - Previous reports from several laboratories have demonstrated the presence of many lipid-metabolizing enzymes in myelin, including all the enzymes needed to convert diacylglycerol to phosphatidylcholine and phosphatidylethanolamine. Axonal transport studies had suggested the presence of additional enzymes which incorporate acyl chains into specific phospholipids of myelin. We report here evidence for one such group of enzymes, the acyl-CoA:lysophospholipid acyltransferases. At the same time, activity of acyl-CoA:sn-glycerol-3-phosphate acyltransferase was negligible in myelin. Oleoyl-CoA and arachidonoyl-CoA were both active substrates for transfer of acyl chains to lysophosphatidylcholine and lysophosphatidylinositol. Activity in myelin varied from 7 to 19% of microsomal activity, values well above the likely level of microsomal contamination as judged by microsomal markers. Additional evidence for a myelin locus came from assays at sequential stages of purification and from mixing experiments. Arachidonoyl-CoA was somewhat more reactive than oleoyl-CoA toward lysophosphatidylcholine; the myelin Km for these two CoA derivatives was 98 microM and 6.6 microM, respectively. Activity with lysophosphatidylinositol as substrate was approximately 40% of that with lysophosphatidylcholine in myelin, whereas activities with lysophosphatidylethanolamine and lysophosphatidylserine were considerably less. PMID- 2908894 TI - Sodium-dependent uptake of nucleosides by dissociated brain cells from the rat. AB - Sodium-dependent 3H-labeled nucleoside transport was studied using a mixed population of dissociated brain cells from adult rats. The accumulation of [3H]adenosine during brief (15-s) incubation periods was significantly greater in the presence of 110 mM Na+ than in its absence. This occurred at substrate concentrations that ranged from 0.25 to 100 microM. Similar findings were observed for the rapid accumulation of [3H]uridine. Kinetically, the rapid accumulation of [3H]adenosine in both the absence and the presence of Na+ was best described by a two-component system. In the presence of Na+, the KT and Vmax values for the high-affinity affinity component were 0.9 microM and 8.9 pmol/mg of protein/15 s, and those for the low-affinity component were 313 microM and 3,428 pmol/mg of protein/15 s, respectively. In the absence of Na+, the KT value for the high-affinity component was significantly higher (1.8 microM). [3H]Uridine accumulation was best described kinetically by a one-component system that in the presence of Na+ had KT and Vmax values of 1.0 mM and 2.6 nmol/mg of protein/15 s, respectively. As was found for [3H]adenosine, in the absence of Na+, the KT value was significantly higher (1.8 mM). The sodium-dependent transport of [3H]adenosine was inhibitable by ouabain and 2,4-dinitrophenol. Of the three nucleoside transport inhibitors tested, only nitrobenzylthioninosine demonstrated high affinity and selectivity in blocking the sodium component. Thus, high-affinity sodium-dependent nucleoside transport systems, in addition to facilitated diffusion systems, exist on brain cells from adult rats. PMID- 2908895 TI - Axolinin localization in the nervous tissue of squid revealed by monoclonal antibodies specific for axolinin: cellular and subcellular localization of axolinin in the squid neuron. AB - Cellular and subcellular distributions of axolinin, the 260-kilodalton (kD) microtubule-associated glycoprotein originally purified from squid axons, in various squid tissues such as optical lobes, bundles of small nerve fibers (fin nerves), giant stellate ganglia, skin, muscle, liver, and gill, were immunologically studied using monoclonal antibodies specifically recognizing the polypeptide chain of axolinin. The following results were obtained: (1) Axolinin is confined to squid neurons and skin; (2) axolinin is localized in the axon whereas another 260-kD microtubule-associated protein, MAP B, is localized in the cell bodies; and (3) axolinin is localized mainly in the peripheral part of the axoplasm of the squid giant axon. The last result has confirmed our previous conclusion obtained using polyclonal antisera against axolinin, which contain antibodies recognizing not only axolinin-specific epitopes but also nonspecific epitopes. The physiological importance of the localization of axolinin in axons and the skin is discussed based on its possible relationship to excitability function. PMID- 2908896 TI - Experimental increase of neurofilament transport rate: decreases in neurofilament number and in axon diameter. AB - In 2,5-hexanedione (2,5-HD)-induced axonal neuropathy, the rate of neurofilament (NF) transport increases in optic axons. To test the prediction that increases in the rate of polymer transport in any one locality of the axon lead directly to a decrease in the number of NF in that locality, NF and microtubules (MT) were quantitatively analyzed in axonal cross sections. In 2,5-HD axons the number of NF was 38% of that in control axons while the number of MT was not significantly changed; it appears that the drug treatment decreases NF number in the proximal axon regions, most directly through an increase in rate of NF transport. In those regions, the cross-sectional areas of the 2,5-HD-treated axons were 45% smaller than those of control axons; although the axons had shrunk in diameter, they retained their normal cylindrical shapes as measured by the index of circularity. Reduced internal expansive forces in the axon, working in conjunction with the normal external compressive forces, appear to reduce the radius of the axon. Quantitative analyses demonstrated that the average and the maximum lateral spacings between NF-NF, NF-MT, and MT-MT were all 30% larger in 2,5-HD-treated axons than in control axons. This suggests that polymers are relatively free to move laterally away from one another and to fill the available space within the axon. These observations are not consistent with models wherein 2,5-HD acts to crosslink the NF into an immobile network that can no longer advance within the axon. Instead, it appears more likely that 2,5-HD acts selectively on the interaction between some NF and the slow transport mechanism to increase the rate of NF transport. PMID- 2908897 TI - Morphologic alterations in rat brain following systemic and intraventricular methotrexate injection: light and electron microscopic studies. AB - To determine the morphological substrate of acute methotrexate (MTX) encephalopathy, light and electron microscopic studies were performed on rat brains after short-term intraperitoneal (IP) and intraventricular (IV) injections of MTX. In both models, Alzheimer type II astrocytosis was the initial and major pathologic alteration seen by light microscopy. The neurons, oligodendrocytes, myelin and endothelial cells were relatively spared. Ultrastructural studies showed pleomorphism and condensation of mitochondria, membrane-bound vacuoles, prominent stacks of sparsely granular, rough endoplasmic reticulum and progressive hydropic swelling of astrocytic perikarya and their processes. The astroglial alterations were reversible after cessation of the drug but persisted for a longer time with repeated IP administration. Gastrointestinal complications and overall mortality were also greater with higher doses and increasing frequency of IP MTX injection. White matter necrosis was noted only after IV injection of high-dose MTX. The neuropathologic changes of MTX leukoencephalopathy can be replicated in an animal model by IV injection of the drug. The reversibility of the changes that were seen following IP administration correlates with the transient neurologic deficits observed in some patients after high-dose systemic MTX therapy. The initially selective astroglial effect suggests that astrocytes might be a target for MTX toxicity, although other central nervous system components may also be adversely affected by the drug. PMID- 2908898 TI - Stimulation of glucose analogue uptake by cerebral microvessel endothelial cells by a product released by astrocytes. AB - Astroglial cells, both normal and neoplastic, secreted a product that stimulated glucose uptake by cerebral microvessel endothelial cells by 23% and 50%, respectively. Neither cerebral microvessel smooth muscle cells nor oligodendrocytes affected endothelial cell glucose uptake. The astrocytic product(s) did not affect glucose uptake by aortic endothelial cells. The effect on the cerebral microvessel endothelial cells increased with increasing time of exposure of the cells to the astroglial product(s), and required the constant presence of the astrocytic product to be maintained. The presence of a protein synthesis inhibitor during endothelial cell exposure to the astroglial conditioned medium blocked the stimulation of glucose uptake. Treatment of the astrocytic product with a protease destroyed its effectiveness. These results support the hypothesis that astrocytes induce the expression of at least one blood-brain barrier property by the cerebral microvasculature, and suggest that this induction may be produced by a protein released by the astrocytes. PMID- 2908899 TI - Cellular changes during repair of a cryogenic spinal cord injury in the rat: an electron microscopic study. AB - Cryogenic injury of adult, rat spinal cord was produced under controlled non invasive conditions to study repair and regeneration in adult, mammalian central nervous tissue in which tissue continuity and integrity are relatively preserved. Under these experimental conditions axons and myelin are destroyed, a matrix of glial cells is preserved, and regrowth of axons is apparent. Electron microscopic studies at 7, 15, 30 and 60 days post-injury demonstrate axonal structures indicative of regrowth, astrocytic structures which appear to provide support to both matrix and axons and myelination of axons by both oligodendrocytes and Schwann cells. These cellular events restore much of the normal structure within the injured area up to its junction with the Wallerian zone. In this junctional zone morphologic evidence may indicate continuing cellular activity, even at 60 days, in axons, astrocytes and myelinating cells. These studies suggest that under ideal conditions damaged axons may be capable of regeneration within the adult mammalian central nervous system and that this model provides an opportunity to define some of the mechanisms. PMID- 2908900 TI - Transpedicular screw fixation. AB - Spinal fixation employing transpedicular screws has recently been the focus of increased attention at various institutions throughout the world, but concerns about the safety and efficacy of transpedicular screws linger. This study was undertaken to address some of these concerns. The study included evaluation of the internal and external morphology of the vertebral pedicles, which revealed that adequate bone stock is generally available at T2, T7, T12, and L1-L5 spinal levels to accept screws in the 4-7-mm diameter range. The pedicle was observed to be composed of abundant cancellous bone internally with relatively thick cortical walls. The method of pilot hole preparation for pedicle screws was also examined. Screws inserted in pilot holes prepared with a 3.4-mm blunt probe (ganglion knife) resulted in higher pullout forces in eight of 10 trials as compared with those with pilot holes prepared using a 3.2-mm drill. Furthermore, the probes afford greater control of hole depth and alignment. Fatigue studies on three screw designs revealed a graduation of strength between a 7.0-mm pedicle screw, a 5.5-mm pedicle screw, and a modified 6.5-mm cancellous lag screw. The modified cancellous lag screw has an inherent stress riser that affected fatigue life. It was noted that extreme care must be exercised to prevent bending of the pedicle screws during implantation. If bending occurs one can expect a 50% reduction in the number of cycles to failure. PMID- 2908901 TI - Dynamic changes in the dimensions of the lumbar spinal canal: an experimental study in vitro. AB - The variation in the dimensions of the lumbar spinal canal under both flexion extension and axial compression-distraction was studied using computerized tomography (CT) scans in human cadaver lumbar spine specimens. In 3-mm-thick CT slices through the disk at L3-L4, the cross-sectional area of the spinal canal was reduced by around 40 mm2, corresponding to a 16% reduction of the initial area when the lumbar spines were moved both from flexion to extension and from distraction to compression. A corresponding reduction in the midsagittal diameter of the canal of 2 mm was found. During these motions, the ligamentum flavum did not appear to be a significant factor for the dynamic changes affecting the dimensions of the canal. This held true even after the disk had been excised in order to produce a total collapse of the disk space. PMID- 2908902 TI - An electron microscopic study of the changes observed in osteocytes under ischemic conditions. AB - The purpose of this study was to observe the process of ischemia in osteocytes using light and electron microscopy and to compare the changes in these ischemic osteocytes with those in other types of osteocytes (i.e., degenerative osteocytes in physiological states, steroid-induced lipid-accumulating osteocytes) that have been previously reported. Five female Japanese white rabbits were used in this study. Osteochondral chips were taken from one side of the femoral condyle, covered with Millipore filters, and then inserted into the other side of the knee joint. These tissues were examined after 12 h and after 2, 5, 8, and 14 days of ischemia under both light and electron microscopy. Under light microscopy, osteocytes and lacunae were classified into four types: normal osteocyte, pyknotic osteocyte, pale osteocyte, and empty osteocyte lacuna. The number of each type of osteocyte (or lacuna) in a settled area was counted. The ratio of normal osteocytes decreased significantly (p less than 0.001) after the second day of ischemia. Pyknotic osteocytes increased at 12 h (p less than 0.01) and 2 days (p less than 0.001) of ischemia. On the fifth day of ischemia, the percentage of pale osteocytes reached a peak. This was followed by a gradual increase in the number of empty lacunae. On the fourteenth day of ischemia, empty lacunae constituted greater than 40% of the cell types. When viewed by electron microscopy, these necrotic osteocytes were similar to the degenerative osteocytes that have been observed in physiological states and apparently different from lipid-accumulating osteocytes. The results suggested that there could be at least two types of necrotic processes in osteocytes that eventually lead to cell death. PMID- 2908903 TI - Internal deformations of intact and denucleated human lumbar discs subjected to compression, flexion, and extension loads. AB - Three rows of six evenly spaced 0.5 mm metal beads were implanted midsagittally into the discs of ten L4-5 human lumbar motion segments. The intradiscal bead displacements in response to compression, flexion, and extension loads were obtained by digitizing the bead positions from sagittal plane radiographs taken before and during the load application. Each disc was denucleated and the loading process was repeated. For the intact discs, in compression, the intradiscal bead displacements were predominantly anterior. In flexion, the beads in the center of the disc moved posteriorly whereas the beads closer to the periphery of the disc moved anteriorly. In extension, the central beads moved anteriorly and the beads closer to the periphery of the disc moved posteriorly. After denucleation, the bead displacements for compression and flexion implied an inward bulging of the inner wall of the annulus, despite outward bulging of the disc surface. We hypothesize that the inward bulging causes radial tensile stresses within the disc, leading to disruption of adjacent layers of annulus. PMID- 2908904 TI - Tibial anatomy and functional axes. AB - Articular geometry of the tibia has been studied in relation to the functional axis and extra-articular bone landmarks, using a Cartesian coordinate system. Thirty-one cadaver limbs were used, 26 of them paired. The donor age range was 61 to 89 years (17 females, 14 males), none of whom showed evidence of significant arthritic deterioration. Most linear parameters were greater in males than females (p less than 0.005), and correlations between these parameters were noted, e.g., tibial length versus plateau width (r = 0.7, p less than 0.01) with both genders combined. Gender differences occurred in only two of the angular parameters--tibial torsion (p less than 0.025) and foot rotation (p less than 0.005). For the latter, mean rotation was internal (-5 degrees) for males, and external (11 degrees) for females. No correlations between angular parameters were found. In the paired limbs, there was asymmetrical distribution of just two parameters--varus tilt of the tibial plateau margins (p less than 0.005) and lateral deviation of the tuberosity (p less than 0.025). The data complement a previous report on the femur. These studies are relevant to the kinematics of the lower limb, design and sizing of resurfacing components, and possibly to the pathogenesis of osteoarthritis. PMID- 2908905 TI - Ingredients of a successful grant application to the National Institutes of Health. AB - Many factors determine the scientific merit of an NIH research grant application. This paper is intended to help optimize the organization and logical development of investigators' research ideas so that grant applications will be evaluated by the reviewers in as favorable a light as possible. The ingredients of a successful grant application are good ideas, good science, and a good application. The research should be based on a significant hypothesis and, if possible, oriented towards uncovering an important biological mechanism. Specific methods should be directly related to each aim of the project. Likewise, the specific aims should be related to each hypothesis. All aspects of the application should be clear and focused. It is best to define all assumptions, limitations, and alternative approaches. In general, the best philosophy is for the applicant to address all possible problems before the reviewers. PMID- 2908906 TI - Blood indices of muscle injury associated with eccentric muscle contractions. AB - Serum muscle enzyme activities of eight healthy men (22-32 years old) were measured before and 48 h after separate bouts of repetitive concentric, eccentric, and isometric contractions of the lower leg anterior compartments. Serum creatine kinase and glutamic oxaloacetic acid transaminase levels were both elevated 2 days after the eccentric exercise regimen, exclusively (36 and 17%, respectively). Lactic dehydrogenase levels were not affected by any of the protocols. Delayed muscle soreness was exclusively reported from the eccentrically exercised limb. We suggest that the high tensions developed during eccentric exercise cause mechanical damage, possibly including sarcolemmal degeneration. Subsequently, muscle enzymes are released to the blood. We conclude that postexercise serum levels of some muscle enzymes, at the time of maximal soreness, are qualitative markers of muscle damage. PMID- 2908907 TI - Articular cartilage and intervertebral disc proteoglycans differ in structure: an electron microscopic study. AB - Articular cartilage and the intervertebral disc tissues have different material and biological properties and different patterns of aging and degeneration. To determine if the proteoglycans of these tissues differ in structure, we used the electron microscopic monolayer technique to compare baboon articular cartilage proteoglycans with baboon annulus fibrosus, transition zone, and nucleus pulposus proteoglycans. Intervertebral disc and articular cartilage proteoglycans differed significantly. Articular cartilage contained large proteoglycan aggregates formed from hyaluronic acid central filaments, multiple monomers, and large nonaggregated monomers. These molecules were identical to those of nasal cartilage, growth plate cartilage, chondrosarcomas, or menisci. In contrast, the intervertebral disc tissues contained only nonaggregated proteoglycan monomers and clusters of monomers without apparent central filaments. Intervertebral disc nonaggregated monomers were shorter and more variable in length than those from articular cartilage, and nucleus pulposus nonaggregated monomers were even shorter and more variable in length than transition zone and annulus fibrosus monomers. These observations suggest that significant differences in proteoglycan metabolism exist between articular cartilage and intervertebral disc. PMID- 2908908 TI - Electromyographic study of the anterior cruciate ligament-hamstrings synergy during isometric knee extension. AB - The purpose of this investigation was to determine the role the hamstrings group may play in augmenting passive articular mechanisms during activity in which anterior drawer force may detrimentally affect the anterior cruciate ligament (ACL). Nine male subjects performed non-weight-bearing isometric knee extension at 10% increments of maximum voluntary contraction (MVC). Electromyographic (EMG) signals were detected and recorded from the vastus lateralis, vastus medialis oblique, vastus medialis longus, and the long head of the biceps femoris. The EMG signals were rectified and integrated over 1000 ms and normalized to subject specific values. The data were subjected to a repeated-measures analysis of variance. The results demonstrated that expected significant increases in quadriceps excitation accompanied increases in knee extensor torque. Hamstrings excitation was not found to change significantly (total change = 3.4%). It was concluded that functionally adequate knees do not require posterior drawer force in excess of that provided passively by articular structures. PMID- 2908910 TI - Effects of indomethacin on bone ingrowth. AB - The effects of indomethacin, a nonsteroidal antiinflammatory agent, on bone ingrowth were studied using a rabbit animal model and a porous cylindrical implant system. Bone ingrowth was found to be independent of pore size in the range tested (0.6-1.0 mm). In the control (placebo-treated) group, there was a significant increase in bone ingrowth between the 2- and 8-week groups of animals. However, in the indomethacin-treated group, there was no increase in bone ingrowth with time. PMID- 2908909 TI - The effects of demineralized bone matrix and direct current on an "in vivo" culture of bone marrow cells. AB - Bone marrow cells (BMCs) from rabbit femora and tibiae were grown in diffusion chambers implanted in rabbit muscle. At 42 days 80% of the BMC chambers exhibited cartilage formation within them. Demineralized bone matrix added to the marrow cell suspension in the chamber accelerated the appearance and increased the number of chambers with cartilage. Mineralization of the cartilage also occurred earlier in the chambers with bone matrix. In a second experiment, a 5-microA direct current cathode in the bone marrow chamber increased the number of chambers containing cartilage from 50 to 80% at day 25. Mineralization also occurred earlier in the chambers with direct current. PMID- 2908911 TI - Nonlinear viscoelastic properties of articular cartilage in shear. AB - The strain dependence of the intrinsic viscoelastic properties of the cartilage matrix in shear was investigated. Stress relaxation experiments were performed on bovine articular cartilage at shear strains ranging from approximately 3% to 16%. The tissue was found to exhibit nonlinear strain-dependent viscoelastic behavior, with the nonlinearity occurring primarily in the short-time transient during stress relaxation. In addition, the equilibrium stress was found to fit a quadratic relation with strain. This relationship was noted to be nearly linear with strain from 3% to 16%. The instantaneous stress was seen to be highly nonlinear, and followed a cubic relationship with applied shear strain. Fung's quasilinear theory can be used to describe the stress relaxation response over the range of strains examined when a nonlinear regression is performed to determine an "average" normalized relaxation function. Alternately, strain dependence can be incorporated into the model to describe and predict more accurately the strain-dependent stress relaxation response. PMID- 2908912 TI - Treatment of antigen-induced arthritis in rabbits with dysprosium-165-ferric hydroxide macroaggregates. AB - Dysprosium-165-ferric hydroxide macroaggregates (165Dy-FHMA) was used as an agent of radiation synovectomy in an antigen-induced arthritis model in New Zealand white rabbits. Animals were killed up to 6 months after treatment. 165Dy-FHMA was found to have a potent but temporary antiinflammatory effect on synovium for up to 3 months after treatment. Treated knees also showed significant preservation of articular cartilage architecture and proteoglycan content compared with untreated controls, but only during the first 3 months after treatment. In animals killed 3 and 6 months after treatment there were only minimal differences between the treated and untreated knees, indicating that the antiinflammatory effects on synovial tissue and articular cartilage preservation were not sustained. PMID- 2908913 TI - Canine bone blood flow estimated with microspheres. AB - Blood flow rate in the periosteal and endosteal cortices of the diaphysis of long bones was determined in eight anesthetized adult dogs using the radioactively labeled microsphere method. The flow rate in endosteal and periosteal cortices is not significantly different unless the endosteal cortex contains cancellous bone from the medullary cavity. The highest flow rate is in the ulna, with 6.50 ml/min/100 g for the endosteal cortex and 5.15 ml/min/100 g for the periosteal cortex. The lowest flow rate is in the femur, with 2.89 ml/min/100 g for the endosteal cortex and 2.29 ml/min/100 g for the periosteal cortex. The results of this study indicate that variation of blood flow does exist between bones of dogs. However, the flow rates of individual bone on the left and right sides in the same dog are not significantly different. This indicates that the data are reproducible and reliable, and differences are not an inaccuracy of the radioactively labeled microsphere method. The results also demonstrate that there are no significant differences in bone blood flow as measured with small numbers (fewer than 400 microspheres per sample) and large numbers (more than 400 microspheres per sample) of microspheres. The adequate number of microspheres in each bone sample is 150-250. Therefore, a dose of 0.5 x 10(6) spheres/kg body weight can be sufficient. PMID- 2908914 TI - Mechanical properties of primate vascularized vs. nonvascularized patellar tendon grafts; changes over time. AB - Mechanical properties of patellar tendon autografts used to replace the anterior cruciate ligament (ACL) in the cynomolgus monkey were measured at four time periods up to 1 year. The ACL was replaced in each knee with the medial half of the patellar tendon: as a vascularized graft (VG) on one side and as a nonvascularized or free graft (FG) on the other. Postoperative care consisted of 4 weeks of cast immobilization at 30 degrees flexion followed by unrestricted activity in a large cage. Both grafts showed low stiffness and maximum force at 7 weeks (24% and 16% of ACL control values, respectively), increasing to 57% of control ACL stiffness and 39% of control maximum force by 1 year. Corresponding material properties, modulus and maximum stress, also increased over time, but at 1 year were only 34% and 26% of ACL values, respectively. The results indicate that retaining vascularity does not prevent significant reduction in graft properties that occur postoperatively, nor does it accelerate the return in strength and stiffness. Tissue stiffness, which returns earlier than maximum force and joint anteroposterior (AP) force displacement data, should be routinely reported in any healing study. Finally, in studies of this kind, the large variation in the results makes sampling only one or two animals from each time period unreliable. PMID- 2908915 TI - Prevention of ligament and meniscus atrophy by active joint motion in a non weight-bearing model. AB - This study describes the effect of active joint motion on the maintenance of ligament and meniscus mass in a non-weight-bearing model of disuse. Denervation and fixation models of immobilization have shown that resorption of isotope and atrophy of mass occurred for hard tissue (bone) and soft tissues (ligament, tendon, or meniscus). A unilateral ankle disarticulation model of disuse that maintains active knee motion without weight bearing was studied for 8 weeks in dogs that were chronically prelabeled with three different isotopes. The effects of non-weight-bearing without denervation or fixation were analyzed for the resorption of isotopes, and net atrophy of bone mass (femur or tibia) and soft tissue mass (collateral or cruciate ligaments, menisci). A large and similar loss of all three isotopes, as well as collagen and calcium mass occurred for whole femur and tibia; this indicated that mass loss was equivalent to bone resorption and suggests little replacement with new bone. No loss of isotope or mass per whole tissue occurred for the collateral and cruciate ligaments or menisci. The strength of the femur-anterior cruciate ligament-tibia complex was analyzed by a tensile failure test when a fast rate of deformation was applied; the results did not differ qualitatively or quantitatively between control and experimental limbs. The absence of weight bearing for 8 weeks resulted in marked bone atrophy without resorption or atrophy of soft tissues, or decrease of the mechanical strength for the femur-ligament-tibia complex. PMID- 2908916 TI - Gain in mass density of bone following strenuous physical activity. AB - A group of 223 military recruits aged 18-21 years underwent strenuous physical training for a period of 14 weeks. The absolute bone density of the distal tibia in both lower limbs was measured before the training period and at its end. The density was determined by the Compton scattering technique, which has been developed in our laboratory; this method provides the bone mass of all bone constituents per unit volume. The distribution curve of the bone density in both tibiae shifted to higher values at the end of the training period. The mean bone density in the right and left tibia increased significantly by 7.5%. This study indicates that following an intensive physical exercise regime, a significant increase in the mass density of bone can be obtained in young adults within a short period. PMID- 2908917 TI - Nonalcoholic carbonated beverage consumption and bone fractures among women former college athletes. AB - We report on data relating to nonalcoholic carbonated beverage consumption and bone fractures in 5,398 college alumnae, 2,622 former college athletes and 2,776 nonathletes, who responded to a detailed mailed questionnaire. A statistically significant association between nonalcoholic carbonated beverage consumption and bone fractures was found only in the former athletes, not the nonathletes. Among the athletes, the age-adjusted odds ratio (OR) for the association of drinkers (yes/no) with any fracture (yes/no) was 1.35, 95% confidence limits (CL) (1.14, 1.59). The dose-response relationship between the amount of carbonated beverages consumed daily and the number of bone fractures of the athletes was also statistically significant. Results of multiple logistic regression analysis, which included only alumnae greater than or equal to 50 years of age and which controlled for current exercise and other potential confounding factors, were as follows: (a) for athletes, the OR for the association of drinking nonalcoholic carbonated beverages and a first bone fracture at or after age 40 was 2.28, 95% CL (1.36, 3.84); (b) for all alumnae, a low milk diet was a risk factor for first bone fractures at or after age 40, OR = 1.92, 95% CL (1.15, 3.16); (c) former college athletes had a significantly lower risk of first fractures at or after age 40 than did nonathletes; OR = 0.63, 95% CL (0.40, 0.99). The deleterious effect of nonalcoholic carbonated beverage consumption on the risk of bone fractures has not been reported, as far as we know.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2908918 TI - Should inferences from observational study of treatment results be applied in osteosarcoma? PMID- 2908919 TI - Is alcohol consumption related to breast cancer? Results from the Framingham Heart Study. AB - We studied the relation between alcohol consumption and breast cancer among women in the Framingham Heart Study cohort. A total of 2,636 women aged 31-64 years provided information on alcohol consumption at the second biennial examination. They were followed for up to 32 years; during this period, breast cancer was diagnosed in 143 of these women. Alcohol intake was also assessed at 10 and 20 years of follow-up and every 2 years thereafter. In analyses using only baseline alcohol intake, the multiple risk factor-adjusted relative risk (RR) estimate of breast cancer for any drinking, compared with nondrinking, was 0.8 [95% confidence interval (CI), 0.5-1.1]. For three levels of alcohol intake (0.1-1.4 g/day, 1.5-4.9 g/day, and greater than or equal to 5.0 g/day), the baseline analyses yielded RRs (vs. nondrinking) of 1.0 (CI, 0.6-1.5), 0.7 (CI, 0.4-1.1), and 0.6 (CI, 0.4-1.0), respectively. In analyses incorporating repeated measures of alcohol, the comparable RRs were 0.9 (CI, 0.6-1.2) for any drinking (vs. nondrinking) and 0.7 (CI, 0.4-1.4), 1.1 (CI, 0.7-1.8), and 0.8 (CI, 0.5-1.2), respectively, for the three levels of intake (vs. nondrinking). Alcohol consumption was not associated with an increased risk of breast cancer in this cohort. PMID- 2908920 TI - Overexpression of N-ras oncogene and epidermal growth factor receptor gene in human glioblastomas. AB - Five human glioblastoma cell lines were analyzed for oncogene activation with a panel of probes. Abnormal expression of the epidermal growth factor receptor (EGFr) gene was detected in four of five lines; N-ras oncogene overexpression was found in all five cell lines. These results were subsequently confirmed with fresh brain tumor and nonneoplastic brain tissue biopsy samples; increased expression of the N-ras proto-oncogene was observed in five of five glioblastomas, all of which also showed EGFr gene overexpression, but not in well differentiated gliomas or in nonneoplastic brain tissue specimens. No significant differences in Ha-ras and Ki-ras expression were observed. Preliminary histochemical observations showed that intracellular levels of transforming growth factor alpha, a putative biochemical link between these two oncogenes, were significantly higher in glioblastoma cells than in controls. PMID- 2908921 TI - Chromosome 9p and hereditary cutaneous malignant melanoma. PMID- 2908922 TI - The ends of La Crosse virus genome and antigenome RNAs within nucleocapsids are base paired. AB - The three La Crosse virus genomes are found as circular structures in the electron microscope, and the RNA ends of at least the small (S) and medium (M) segments are highly complementary. When examined for psoralen cross-linking, about half of the S, at most 1 to 2% of the M, and none of the large (L) nucleocapsid RNAs could be cross-linked in virions or at late times intracellularly, under conditions in which each free RNA reacted completely. For the S segment, genomes and antigenomes first detected intracellularly could not be cross-linked at all, and their cross-linkability increased gradually with time. Antigenomes behaved similarly to genomes in all respects. It appears that the majority of all three segments are base paired at their ends and that the limited cross-linkability reflects the accessability of the RNA within nucleocapsids to psoralen. The gradual increase in cross-linkability may be important in persistent mosquito cell infection, in which it correlates with decreased S mRNA synthesis rates, and may be part of the mechanism which this infection becomes self-limiting. The implications of double-stranded RNA panhandles within nucleocapsids are discussed. PMID- 2908923 TI - Effect of mutations and deletions in a bicistronic mRNA on the synthesis of influenza B virus NB and NA glycoproteins. AB - The mRNA derived from influenza B virus RNA segment 6 is functionally bicistronic and encodes the NB and NA glycoproteins in different, overlapping reading frames. NB protein synthesis is initiated at the 5'-proximal AUG codon, and 4 nucleotides downstream there is a second AUG codon which is used to initiate NA protein synthesis. The nucleotide sequence context of the first AUG codon conforms closely with the established 5'-CC(A/G)CCAUGG-3' consensus sequence (M. Kozak, Nucleic Acids Res. 15:8125-8148, 1987), which should favor initiation of NB protein synthesis at this site, yet NB and NA are found to accumulate in approximately equal amounts in infected cells. To determine the features important for allowing initiation at the second 5'-proximal AUG codon, we made changes in the 5'-terminal region of the mRNA, including deletions, insertions, and site-specific mutations. The recombinant DNA molecules were expressed in eucaryotic cells, and the accumulation of NB and NA was quantitated. The data indicate that changes in the immediate sequence around the first AUG codon do not make a large difference in the amounts of NB and NA that accumulate, but that when the first AUG codon is displaced from its normal position it is now quite efficient at preventing downstream initiation events. In addition, the data indicate that an element of the B/NB/NA mRNA 5' untranslated leader region acts in cis to enhance the expression of NB and NA. PMID- 2908925 TI - Abortive replication of choleraphage phi 149 in Vibrio cholerae biotype el tor. AB - Choleraphage phi 149 adsorbed irreversibly to Vibrio cholerae biotype el tor cells, and 50% of the injected phage DNA bound to the cell membrane. Although no infectious centers were produced at any time during infection, the host macromolecular syntheses were shut off and the host DNA underwent chloramphenicol inhibitable degradation. Synthesis of monomeric phage DNA continued similar to that observed in the permissive host. However, the concatemeric DNA intermediates produced were unstable and could not be chased to mature phage DNA. Pulse labeling of UV-irradiated infected cells at different times during infection allowed identification of phage-specific proteins made in this nonpermissive host. Although most of the early proteins were made, only some of the late proteins were transiently synthesized. PMID- 2908924 TI - Construction and analysis of deletion mutations in the U5 region of Moloney murine leukemia virus: effects on RNA packaging and reverse transcription. AB - A collection of deletion mutations was generated in the U5 region of cloned DNA copies of Moloney murine leukemia virus or a related retrovirus. Cell lines expressing the mutant DNAs were generated by cotransformation, and the virions released were characterized biochemically. Deletions in the 5' part of U5 profoundly reduced packaging of the viral RNA into virions; one deletion in the 3' part of U5 did not block packaging but affected reverse transcription. One mutant with a deletion in the central part of U5 was fully viable and served to separate the two functional parts of U5. PMID- 2908926 TI - Identification of a U5-specific sequence required for efficient polyadenylation within the human immunodeficiency virus long terminal repeat. AB - Retrovirus mRNAs are normally polyadenylated within the proviral 3' long terminal repeat (LTR). The site of retrovirus transcript polyadenylation is flanked 3' by an LTR-specific sequence termed the U5 region, but the role of U5 in the determination of polyadenylation efficiency has not been addressed. We have used site-directed mutagenesis of a human immunodeficiency virus LTR to map U5 sequences which are required for efficient polyadenylation within the LTR. These LTR U5 region sequences display homology to a motif termed the G-T cluster, which is known to facilitate the efficient polyadenylation of mRNAs encoded by several cellular and viral genes. These results suggest that the LTR U5 region functions in vivo to permit efficient polyadenylation within the proviral 3' LTR. PMID- 2908927 TI - In vitro transcription of bacteriophage phi 29 DNA: inhibition of early promoters by the viral replication protein p6. AB - The effect of the phi 29 protein p6 on the in vitro initiation of transcription from the main phi 29 promoters was studied. Protein p6 interfered with the transcription from the early promoters C1 and C2, located at the right end of the phi 29 genome. Transcription initiated at the early promoters A1, A2b, and A2c and at the late promoter A3, located at the left region of the viral genome, was not affected by protein p6. These results suggest that protein p6 might play a dual role, acting as a negative modulator of some phi 29 early promoters apart from being a positive modulator of the viral DNA replication. PMID- 2908928 TI - Continent urinary reconstruction in ischiopagus tripus conjoined twins. AB - The principle of the continent urinary reservoir involves use of a variety of intestinal segments providing continence, a mechanism of antireflux and a catheterizable stoma in either an abdominal or pelvic location. This concept was used to create a continent urinary reservoir in a 3-year-old former ischiopagus tripus conjoined twin. The solitary renal unit had been drained into a hydrocolpos with an antirefluxing ureteral reimplantation at separation. The patient remained incontinent through the urogenital sinus. At subsequent reconstruction the posterior aspect of the hydrocolpos was tubularized as a vagina, while the remainder of the hydrocolpos was augmented with ileum to create a urinary reservoir. The conduit was constructed with imbricated ileum, in which myectomy had been performed to allow for easier imbrication and tubularization for a narrow neourethra. A second set of conjoined twins have been separated similarly. Of these twins 1 will undergo creation of a continent urinary reservoir in an identical fashion. This represents the first report of the use of hydrocolpos in the creation of a urinary reservoir. PMID- 2908929 TI - Arteriovenous malformation of the spermatic cord. AB - We report a case of an arteriovenous malformation of the spermatic cord, a lesion that to our knowledge has not been described previously. PMID- 2908930 TI - Recovery of function in a solitary kidney after intra-arterial thrombolytic therapy. AB - Renal artery thromboembolism is a rare event that most often occurs in patients with cardiac dysrhythmias. Surgical thromboembolectomy is risky and medical therapy with intra-arterial thrombolytic agents has become increasingly popular. Although successful clot dissolution has been well documented, renal function often is not recovered. We describe a patient with anuria from thromboembolism to a solitary kidney, treated with low dose intra-arterial streptokinase infusion. There were no adverse effects from therapy and renal function returned to a point where dialysis was no longer required. A review of the literature is included with special attention to various protocols for infusion. Early diagnosis and prompt initiation of therapy may result in clinically significant recovery of renal function. PMID- 2908931 TI - Total replacement of the suprarenal inferior vena cava with an expanded polytetrafluoroethylene tube graft in 2 patients with tumor thrombi from renal cell carcinoma. AB - Total replacement of the suprarenal inferior vena cava using an expanded polytetrafluoroethylene vascular graft was successful in 2 renal cell carcinoma patients with extended tumor thrombi densely adherent to the vena caval wall. Right radical nephrectomy in 1 patient and enucleation of the tumor in the solitary right kidney were performed concomitantly. Both patients are well without tumor recurrence and with good vena caval patency 14 and 6 months postoperatively. This procedure could be a safer mode of operation in cases of extended vena caval involvement by malignant tumors. Total reconstruction of the inferior vena cava enables more radical resection of the tumor. PMID- 2908932 TI - Repeat selective embolization of solitary kidney with renal cell carcinoma: case report. AB - Massive bleeding in a patient with metastatic carcinoma of a solitary kidney may be controlled with transcatheter embolization. Selective occlusion may be done sparing renal parenchyma uninvolved by tumor and avoiding dialysis. We report a case of successful repeated selective embolizations with an excellent quality of life for 18 months. PMID- 2908933 TI - Strictures in the ileal portion of ileocecal conduits in children and young adults. AB - Patients with ileocecal conduits are at risk for development of late complications. We present 3 patients who had strictures in the ileal portion of the ileocecal conduit, leading to deterioration of the upper urinary tract. The pathogenesis of these strictures appears to result from chronic inflammation. Long-term periodic upper urinary tract screening with ultrasonography is important for early detection of this complication. When new or increasing hydronephrosis is found a loopogram or antegrade pyelogram (if the ileocecal valve is competent) should be performed to evaluate the ileal portion of the ileocecal conduit. PMID- 2908934 TI - Arteriovenous malformations of the bladder. AB - We report a rare case of a localized arteriovenous malformation of the bladder mimicking a bladder tumor and presenting with gross hematuria. The mass was successfully resected transurethrally. PMID- 2908935 TI - Papaverine-induced fibrosis of the corpus cavernosum. AB - Intracorporeal papaverine self-injection is a new therapy for erectile dysfunction. Although reports of side effects are few, complications, such as priapism and fibrosis, have been described. We report a case of papaverine induced obliteration of the corpus cavernosum with resulting inability to place a penile prosthesis. PMID- 2908936 TI - Familial torsion of the spermatic cord. AB - Familial spermatic cord torsion is rare. We present the fifth recorded family with this condition. Due to awareness of the condition and its consequences on the part of the family there was minimal delay in presentation and early testicular salvage occurred in all 4 patients. PMID- 2908937 TI - Ureteral injuries complicating vascular surgery: is repair indicated? AB - We have managed 8 patients who sustained an iatrogenic ureteral injury during either placement or revision of a vascular graft. Primary repair was performed in all 5 patients diagnosed at injury. Persistent extravasation necessitating nephrectomy occurred in 2 of these patients. The diagnosis was delayed in 3 patients. Two patients underwent successful ureteral reconstruction and 1 required nephrectomy. Graft complications did not occur. Ureteral repair is recommended as the preferred method to manage ureteral injuries associated with vascular reconstruction. PMID- 2908938 TI - Pheochromocytoma of the prostate: an unusual location. AB - We report a case of pheochromocytoma of the prostate. The clinical presentation, diagnostic evaluation, therapy and pathological findings are discussed. PMID- 2908939 TI - Isolated pulmonary metastases from carcinoma of the prostate: a case report and deoxyribonucleic acid analysis using flow cytometry. AB - We report an unusual case of isolated metastatic prostate adenocarcinoma to the lung and compare the deoxyribonucleic acid content of the primary tumor to the metastases using flow cytometry. PMID- 2908940 TI - Extracorporeal shock wave lithotripsy and residual stone fragments in lower calices. PMID- 2908941 TI - Re: Features of 164 bladder ruptures. PMID- 2908942 TI - Urodynamic studies after intrathecal administration of baclofen and morphine in dogs. AB - The effects of intrathecally administered baclofen and morphine on the lower urinary tract dynamics of anesthetized dogs were investigated by means of cystometrogram and urethral pressure profile measurement. The experiments were performed prior to and 30, 60 and 90 minutes following intrathecal injection of either baclofen (0.03 mg./kg.), morphine (0.03 mg./kg.), or a mixture of the two (0.03 mg./kg. of each drug). Vesical pressure was significantly depressed after either baclofen (p less than 0.005) or morphine (p less than 0.005), while urethral pressure was decreased significantly only following baclofen (p less than 0.025). Administration of a baclofen/morphine admixture resulted in an additive reaction on the urethral pressure profile, compared with the changes brought about by each drug alone. Relaxation of the bladder and reduction in urethral resistance occurred 30 minutes post injection, increasing progressively after 60 and 90 minutes. The results demonstrated that baclofen, by its influence on cord neuron interaction, is capable of inhibiting the activity of the smooth muscle of the normal bladder and urethra, which in the case of the latter became more pronounced when both drugs were administered simultaneously by the intrathecal route. PMID- 2908943 TI - A method for studying pain arising from the urinary bladder in conscious, freely moving rats. AB - A new technique has been developed suitable for quantitative studies on physio pharmacology of pain arising from the urinary bladder in conscious freely-moving rats. The method involves the intravesical instillation of xylene or its vehicle (0.3 cc of silicone oil) through a catheter chronically implanted into the rat bladder. The instillation of xylene (10 to 100%) produced behavioural effects (licking of lower abdomen or perineal region, hind paws hyperextension) suggestive of visceral pain. All the behavioural responses produced by xylene instillation were prevented by extrinsic bladder denervation (pelvic ganglionectomy). Morphine HCl (two to five mg./kg. s.c., 30 min. before) or (+/-) baclofen (2.5-10 mg./kg. s.c., 60 min. before) reduced or abolished the response to xylene instillation, thus indicating that the action of analgesic drugs can be quantitated using the present model. PMID- 2908944 TI - The accuracy of a catheterized residual urine. AB - Residual urine is important in the evaluation of the urological patient. The gold standard to obtain this information is a catheterized specimen. We examined the accuracy of a catheterized value to ascertain whether the bladder was emptied completely. After the bladder was catheterized 10 ml. radiocontrast material were instilled into the bladder to allow radiographic documentation of complete evacuation. We found that 26 per cent of 515 patients evaluated had residual urine after routine attempts were made to evacuate the bladder fully. We conclude that a single residual urine estimate may be inaccurate and one should not always base therapeutic decisions upon any single such measurement. PMID- 2908945 TI - Effects of intravesical instillation of verapamil in patients with detrusor hyperactivity. AB - The effects of verapamil instilled intravesically were investigated in patients with detrusor hyperactivity of neurogenic and non-neurogenic origin. An intermittent, well reproducible cystometric technique with stepwise infusion of fluid was used. Verapamil produced a significant increase of the bladder capacity in patients with detrusor hyperreflexia, but not in patients with detrusor instability. The drug had no significant influence on any other cystometric parameter. It is suggested that pathophysiological differences between hyperactivity of neurogenic and non-neurogenic origin may be responsible for the difference observed. The possible diagnostic and/or therapeutic importance of the present findings remains to be established. PMID- 2908946 TI - Prevention of cancer at the urothelial enteric anastomotic site. AB - An animal model of ureterosigmoidostomy was employed to elucidate the etiology of urinary intestinal anastomotic cancer. One hundred ninety-four rats were divided into five groups: vesicosigmoidostomy rats fed water without drug (controls); those fed ammonium chloride, or sodium bicarbonate, or ascorbic acid; and, finally, vesicosigmoid interposition rats. A significantly decreased incidence of cancer was evident only in the bowel interposition group (p less than 0.001). Ascorbic acid and altered urinary pH were not prophylactic. Possible mechanisms are discussed. PMID- 2908947 TI - Experimental chemotherapy and radiotherapy to paratesticular rhabdomyosarcoma. AB - Experimental chemotherapy and radiotherapy were tried in transplanted tumors derived from a paratesticular embryonal rhabdomyosarcoma. There was no significant difference on the therapeutic effect between a combination chemotherapy composed of vincristine, actinomycin D and cyclophosphamide, so called "VAC" regimen, and a single therapy of radiation. However, morphologic analyses suggest that VAC is effective in embryonal rhabdomyosarcomas in which undifferentiated rhabdomyoblasts predominate, while radiotherapy is preferable for those containing variously differentiated rhabdomyoblasts. PMID- 2908948 TI - Ketoconazole: a possible direct cytotoxic effect on prostate carcinoma cells. AB - Ketoconazole has been recently used in the treatment of advanced prostatic cancer and is believed to exert its effect by inhibition of androgen production. In order to determine whether ketoconazole exerts an additional direct cytotoxic effect on prostate cancer cells, we studied its effect on human hormone independent prostate cancer cell lines (PC-3 and DU-145) in an in vitro clonogenic tumor assay. We showed that clinically achievable doses of ketoconazole caused greater than 90% suppression of tumor colony growth. PMID- 2908949 TI - Superficial bladder cancer treated with bacillus Calmette-Guerin: a multivariate analysis of factors affecting tumor progression. AB - A multivariate analysis was performed on data from 221 patients with superficial bladder tumors (papilloma in 30, grade II to III stage Ta in 51, grade II to III stage Tis in 111 and grade II to III stage T1 in 29) who were treated with intravesical bacillus Calmette-Guerin and followed for a minimum of 24 months or until progression. The purpose of this analysis was to identify prognostic variables predictive of tumor progression defined as muscle invasion, metastasis or endoscopically uncontrolled superficial bladder carcinoma involving the bladder and/or prostatic urethra. Variables examined before bacillus Calmette Guerin, and at 3 and 6 months after bacillus Calmette-Guerin included age, sex, race, purified protein derivative reaction, duration of disease, tumor category, tumor grade, multifocality, results of cytology, flow cytometry, cystoscopy, biopsy, prior chemotherapy and bacillus Calmette-Guerin treatment regimen. Significant variables (Cox regression analysis, p less than 0.07) for tumor progression were before bacillus Calmette-Guerin--stage T1 tumors and duration of disease less than 1 year, at 3 months after bacillus Calmette-Guerin--stage T1 tumor, duration of disease less than 1 year, positive cytology studies and multifocality, and at 6 months after bacillus Calmette-Guerin--stage T1 tumor, positive cytology and positive biopsy other than stage T1 tumors. Prognostic risk groups were best defined at 6 months after bacillus Calmette-Guerin, the probability of tumor progression thereafter being at 1, 3 and 5 years, respectively, as follows: for risk group 1 (T1 tumor)--71, 100 and 100 per cent, for risk group 2 (positive biopsy other than T1 plus positive cytology)--25, 79 and 100 per cent, for risk group 3 (either positive biopsy other than stage T1 or positive cytology studies)--18, 40 and greater than 81 per cent, and for risk group 4 (negative biopsy and negative cytology studies)--2, 11 and 26 per cent, respectively. Evaluation of patients with superficial bladder carcinoma at 6 months after intravesical bacillus Calmette-Guerin therapy identifies the probability of tumor progression. Patients at high risk for tumor progression require alternative treatment strategies, whereas low risk patients can be observed for further therapy if necessary. PMID- 2908950 TI - Cisplatin, cyclophosphamide and doxorubicin chemotherapy for unresectable urothelial tumors: the M.D. Anderson experience. AB - We reviewed retrospectively 97 patients treated with cisplatin, cyclophosphamide and doxorubicin chemotherapy at our hospital to evaluate predictive variables for response to chemotherapy and long-term survival free of disease. Histological subtype influenced response: 70 per cent of the patients with pure transitional cell carcinoma achieved an objective response (partial remission 31 per cent and complete remission 39 per cent), whereas 45 per cent of those with mixed tumors achieved response (partial remission 20 per cent and complete remission 25 per cent). Patients with nodal metastases only had an equal over-all response rate to those with visceral metastasis (64 versus 62 per cent) but patients with nodal metastases had a higher complete remission rate (45 versus 20 per cent). A total of 35 patients (36 per cent) achieved a complete response. In 17 of the 35 patients the duration of response was less than 100 weeks and 18 (51 per cent) have survived longer than 100 weeks. Of the 17 patients with a survival free of disease of less than 100 weeks 16 died of recurrent urothelial tumors and 1 died of a second primary tumor. Among the patients with a survival free of disease of longer than 100 weeks only 2 have had recurrent urothelial tumors; 72 per cent of the patients in this category remain free of disease. Patients with pure transitional cell carcinoma were represented in equal frequency among patients achieving a durable complete remission and those with a complete remission of less than 100 weeks. These data demonstrate the ability of cisplatin, cyclophosphamide and doxorubicin combination chemotherapy to achieve a complete remission and long-term survival free of disease among select patients with unresectable urothelial tumors. PMID- 2908951 TI - Adrenergic innervation of the striated muscle of the intrinsic external urethral sphincter from patients with lower motor spinal cord lesion. AB - The adrenergic innervation of smooth and striated muscle components of the intrinsic external urethral sphincter from patients with suprasacral lesions and detrusor-sphincter dyssynergia has been described previously, when no adrenergic nerves were found associated with striated muscle fibers. In our study the intrinsic external urethral sphincter from patients with lower motor neuron lesions and detrusor areflexia was studied histochemically using the glyoxylic acid method to visualize catecholamines. Varicose adrenergic nerves were demonstrated in the smooth muscle. Adrenergic nerve fibers also were found along the edge of individual striated muscle fibers as well as around striated muscle bundles. Blood vessels in both regions of the urethral sphincter were innervated by adrenergic nerves. We conclude that in patients with lower motor neuron lesions and detrusor areflexia there is a substantial invasion by adrenergic nerve fibers in relation to smooth and striated muscle in the urethra, although the function of the nerve fibers is not known. PMID- 2908952 TI - Internal urethrotomy as a complementary method after urethroplasties for posterior urethral stenosis. AB - Failure of the treatment of posterior urethral stenosis ranges from 10 to 30 per cent. Strictures secondary to pull-through or transpubic urethroplasty are difficult to manage. The management of these strictures is reviewed in 21 children and 84 adults. Of the 105 patients 69 had been treated previously by a perineal pull-through technique and 36 by transpubic urethroplasty. A total of 18 patients (10 in the transpubic and 8 in the pull-through groups) whose results were fair or poor underwent internal urethrotomy with the Sachse knife as a complementary treatment after posterior urethroplasty. Internal urethrotomy provided good results in 8 patients (80 per cent) in the transpubic group and 5 (62.5 per cent) in the pull-through group. None of the patients was incontinent and there was no symptomatic urinary infection postoperatively. PMID- 2908953 TI - Amyloidosis of the urethra. AB - Primary, localized amyloidosis of the urethra is rare. The patient usually presents with hematuria and the appearance of urethral carcinoma. However, the disease is benign and it is treated effectively with local removal. We report our experience with 5 cases. PMID- 2908954 TI - Side effects of self-administration of intracavernous papaverine and phentolamine for the treatment of impotence. AB - Beginning October 1985, 111 men agreed to enter a prospective study of the side effects of low dose papaverine/phentolamine therapy. A total of 46 men dropped out, 30 during the initial phase. The percentage of men with painless nodules almost consistently doubled from one followup examination to the next: 8 per cent at 1 month, 17 per cent at 3 months, 32 per cent at 6 months and 57 per cent at 12 months. The average injection frequency of those with nodules was 2 1/2 times higher than those without nodules. Of the men 41 per cent required an increased dose of medications during followup, and 40 per cent of 50 men had at least 1 abnormality of liver function, most of these involving mild to moderate elevations of alkaline phosphatase and lactic dehydrogenase. Priapism was not encountered during self-injection but it did occur twice in 329 physician administered injections. Careful regular monitoring of patients should continue as some patients enter the second year of treatment. PMID- 2908955 TI - Experience with the Hydroflex penile prosthesis. AB - Between July 1985 and September 1987 we implanted 51 Hydroflex* penile prostheses for treatment of erectile impotence, with a minimum followup of 6 months in all patients and more than 1 year in 43. There have been no mechanical failures and no major complications. Of 47 evaluable patients 38 (81 per cent) are satisfied with the prosthesis. The 9 dissatisfied patients include 3 men who still are experiencing some difficulty operating the pump mechanism and 6 who desired a fuller or stiffer erection than provided by the Hydroflex prosthesis. All of the latter 6 individuals have successfully engaged in intercourse with the Hydroflex device. The patient who previously received a Scott inflatable penile prosthesis may not be as content with the erect state of the Hydroflex device. It also is important to assure adequate distal corporeal length before placement of the Hydroflex prosthesis. PMID- 2908956 TI - Adrenal autotransplantation with attached blood vessels for treatment of Cushing's disease. AB - A case of Cushing's disease was treated successfully by staged total adrenalectomy, left adrenal autotransplantation with the attached blood vessels and pituitary irradiation. In the first stage the left adrenal gland was removed with its attached blood vessels intact, and adrenal autotransplantation then was performed. An end-to-end anastomosis was made between the adrenal central vein and the right inferior epigastric artery. The anastomosis between the right saphenous vein and the adrenal middle artery was accomplished by intussuscepting the artery into the vein followed by suturing. The second stage operation was total right adrenalectomy. Steroid replacement therapy was stopped 7 days postoperatively and all laboratory studies were normal. Two months after total right adrenalectomy the patient had a sensation of facial fullness. Plasma cortisol and 24-hour urinary 17-hydroxycorticosteroid levels were elevated. Part of the graft was excised with the patient under local anesthesia. The symptoms disappeared and the laboratory studies returned to normal. Pituitary irradiation was administered as supplementary treatment of Cushing's disease. This method for the treatment of Cushing's disease has proved feasible. The inguinal region is the optimal site for adrenal autotransplantation. PMID- 2908957 TI - Inflatable penile prostheses in patients undergoing cystoprostatectomy with urethrectomy. AB - When urethrectomy is indicated in the male patient in combination with cystoprostatectomy for diffuse transitional cell carcinoma, an additional challenge to reconstruction and sexual rehabilitation will be encountered. Inflatable penile prostheses were implanted in 19 patients who had undergone cystoprostatectomy with prophylactic urethrectomy. Of the patients 13 underwent cystoprostatectomy with en bloc urethrectomy and delayed placement of an inflatable penile prosthesis. The remaining 6 patients required urethrectomy and simultaneous implantation of an inflatable penile prosthesis 6 to 12 weeks after radical cystectomy. All 19 patients healed appropriately and had an adequate functioning prosthesis. However, results in patients in whom the glandular urethra could be preserved safely were far superior to those in patients requiring total urethrectomy. This was so because of easier and improved cylinder placement with better support to the glans, increased glandular sensation and a more acceptable penile appearance. The inflatable penile prosthesis can be used successfully in the cystourethrectomy patient with gratifying results, especially when the glandular urethra remains intact. PMID- 2908958 TI - Urological applications of human papillomavirus typing using deoxyribonucleic acid probes for the diagnosis and treatment of genital condyloma. AB - The use of deoxyribonucleic acid probes to examine the type of the human papillomavirus genome found in penile lesions is described at a technical level and in a clinical application. At least 40 different types of human papillomavirus have been identified and these types vary not only in their deoxyribonucleic acid base sequences but also in their clinical manifestations. Although deoxyribonucleic acid probes currently have a role only in a research setting, this study delineates the possible role of this technology in a clinical setting to detect subclinical intraurethral human papillomavirus. The results have widespread implications regarding the treatment of condyloma and the associated cervical dysplasia. In this series 25 grossly visible lesions were typed and 85 per cent contained human papillomavirus types 6 and 11. In contrast, microscopic lesions identified in the male partners of women with cervical dysplasia were shown to contain human papillomavirus types 16, 18 or 31 in 60 per cent of the cases. In addition, urethral brushings were obtained and were positive for human papillomavirus in 50 per cent of the cases despite normal urethroscopy. Human papillomavirus types 16, 18 or 31 accounted for 70 per cent of the positive urethral brushings. PMID- 2908959 TI - Radiographic assessment of the vesicourethral anastomosis directing early decatheterization following nerve-sparing radical retropubic prostatectomy. AB - Early decatheterization directed by postoperative gravity cystography in 55 consecutive radical prostatectomy patients is described. The catheter-free status was 22 per cent by postoperative day 8, 62 per cent by postoperative day 11 and 80 per cent by postoperative day 14. Cystograms performed beginning on postoperative day 7 identified 3 groups of patients and dictated their management: 1) no extravasation resulting in immediate catheter removal (36 patients), 2) moderate extravasation requiring repeat cystography leading to decatheterization by postoperative day 15 (9 patients) and 3) severe extravasation necessitating prolonged catheter drainage (8 patients). A decatheterization protocol is presented. PMID- 2908960 TI - Cause-specific actuarial survival analysis: a useful method for reporting survival data in men with clinically localized carcinoma of the prostate. AB - The primary objective of this retrospective 15-year survival analysis of 57 men with clinical stage B1 carcinoma of the prostate undergoing radical prostatectomy between 1951 and 1963 is to compute the cause-specific curve for these men and argue why it is a useful method to report survival data in men with clinically localized prostatic cancer. Historically, survival following radical prostatectomy and radiotherapy has been reported using all cause survival analysis. Cause-specific survival focuses on the impact of a disease process on survival, since men dying of causes unrelated to carcinoma of the prostate are considered lost to followup as of date of death of such unrelated causes. Cause specific survival analysis reduces the impact of age, medical condition and other risk factors on survival rates. The cause-specific 15-year actuarial survival rate in our patients was 86 per cent. The 95 per cent confidence interval for this 15-year survival rate was 76.9 to 90.1 per cent. Based upon this series of patients with clinical stage B1 carcinoma of the prostate who undergo radical prostatectomy one may state that the chance of death of carcinoma of the prostate within 15 years of surgery averages 14 +/- 5 per cent. The cause-specific survival curve reached a plateau at 10 years, indicating that most men who survive 10 years are cured of the disease. With the Cox model regression analysis, mortality in this series was related positively to age at operation when the outcome variable was death of all causes (p equals 0.003) but it was unrelated to age when the outcome variable was prostate cancer mortality (p equals 0.85). Cause-specific survival rates are a more precise indicator of the impact of a therapeutic modality on survival and, therefore, they are useful to report survival data in men with localized carcinoma of the prostate and other disease when death from competing causes is an important consideration. PMID- 2908961 TI - Microwave sterilization: a method for home sterilization of urinary catheters. AB - A standard microwave oven has been used to sterilize catheters used for intermittent self-catheterization. Catheters were incubated for 60 minutes in a suspension of microorganisms isolated from the urine of patients with urinary tract infections. Each catheter was removed from the suspension, placed in a paper bag and microwaved for 0 to 30 minutes. A control catheter was not microwaved. We tested 42 strains of microorganisms to determine the minimum microwaving time needed to sterilize the catheters. Representative urinary isolates of Escherichia coli, and Klebsiella, Proteus, Enterobacter, Pseudomonas, Staphylococcus, Streptococcus and Candida species were tested. Mean sterilization time for all strains was 13.0 minutes (standard deviation +/- 5.7 minutes), with a range of 4.0 to 28.6 minutes. Repeat sterilization in the microwave oven did not affect the integrity of the catheter. A water heat sink of constant volume was required. A home microwave oven may be used as a method to sterilize red rubber catheters for reuse. This technique makes aseptic intermittent self catheterization a practical possibility. PMID- 2908962 TI - Penile retractor. PMID- 2908963 TI - Treatment of congenital penile curvature due to disparate corpora cavernosa by the Nesbit technique: a rule of thumb for the number of wedges of tunica required to achieve correction. AB - Treatment of pure congenital penile curvature due solely to asymmetry of the corpora cavernosa as described by Nesbit lacks precision. Intraoperative verification of Nesbit correction by artificial erection after wedge excision may be impossible because leakage through the sutured corporeal incisions prevents full erection. We present a rule of thumb to calculate the number of 1 cm. wedges of tunica albuginea to be excised to correct an individual deformity. The number of such wedges required is equal to the measured difference in centimeters between the lengths of the asymmetric, concave and convex surfaces of the affected penis, between the pubis and mid glans. Results of application of this principle in 6 patients are presented. PMID- 2908964 TI - Urodynamic and clinical outcome of Kock pouch continent urinary diversion. AB - Urodynamic studies of the Kock pouch were conducted in 20 patients 3 to 36 months after radical cystectomy and urinary diversion for invasive bladder cancer. Functional pouch capacity, intrapouch pressure, maximal nipple pressure, maximal nipple closure pressure and functional nipple length with the pouch filled to capacity were measured. Intermittent involuntary pressure spikes resembling bowel peristaltic waves occurred in 5 patients (25 per cent). The mean functional pouch capacity was 280.0 +/- 119.2 ml. (standard deviation) and mean maximal intra pouch pressure was 41.0 +/- 11.0 cm. water in patients with involuntary pressure spikes. In patients without involuntary pressure spikes these values were 332.7 +/- 114.5 ml. and 11.6 +/- 4.8 cm. water, respectively. For all patients the mean maximal nipple pressure was 72.1 +/- 24.6 cm. water, the mean maximal nipple closure pressure was 58.8 +/- 23.1 cm. water and the mean functional nipple length was 3.4 +/- 0.9 cm. A functional nipple length of less than or equal to 2.5 cm. and/or a low maximal nipple closure pressure (less than 40 cm. water) correlated with a small functional pouch capacity (less than 200 ml.) in 5 patients. Clinically, these 5 patients also required frequent catheterization to provide continence. A maximal nipple closure pressure greater than 60 cm. water and an adequate functional nipple length (greater than 3.0 cm.) correlated with a rather large functional pouch capacity (more than 350 ml.). The degree of continence provided by the Kock pouch appeared to be determined by functional nipple length, maximal nipple closure pressure, functional pouch capacity and maximal intrapouch pressure. PMID- 2908965 TI - Diagnostic and therapeutic technology assessment. Percutaneous lumbar diskectomy for herniated disks. AB - Percutaneous diskectomy, particularly using Onik's nucleotome, has promise. It is too early, however, to decide if the percutaneous approach to reducing lumbar disk herniation will achieve a permanent place in the surgical armamentarium. Nevertheless, it is clear that patient selection is important. At the minimum, an adequate trial of conservative therapy must be followed by diagnostic imaging that documents a herniation that can be treated in this fashion and correlates with the patient's neurological signs and symptoms. If free fragments are found, a laminectomy of some sort will be required to remove the offending material. Patients who are at risk for general anesthesia or may be allergic to chymopapain were mentioned by the panel as special subpopulations for whom the procedure may be indicated despite the lack of wide experience with it. The rapidly rising popularity of automated percutaneous lumbar diskectomy via the nucleotome will hopefully be followed in the near future with larger studies with long-term follow-up. PMID- 2908966 TI - Nonsmokers' rights go international. PMID- 2908967 TI - 'Smokeless cigarette' draws plenty of heat. PMID- 2908968 TI - Environmental challenges to American medicine. PMID- 2908969 TI - Preventive medicine for the 21st century. PMID- 2908970 TI - Physicians should give injections. PMID- 2908971 TI - Amnesty International stands opposed. PMID- 2908972 TI - Do we condone the death penalty? PMID- 2908973 TI - Is the death penalty appropriate? PMID- 2908974 TI - First do no harm. PMID- 2908975 TI - Pet project. PMID- 2908976 TI - Boxing makes more headlines than usual and a lot of the news hasn't been good. PMID- 2908977 TI - If rabbits can regenerate the eye's lens, will science find a way for humans to do it? PMID- 2908978 TI - AIDS' economic, social impact heightens concern. PMID- 2908979 TI - Leads from the MMWR. State-specific estimates of smoking-attributable mortality and years of potential life lost--United States, 1985. PMID- 2908980 TI - Leads from the MMWR. Prevalence of oral lesions and smokeless tobacco use in Northern Plains Indians. PMID- 2908981 TI - Battlefield for the tobacco war. PMID- 2908982 TI - Premier 'smokeless cigarettes' can be used to deliver crack. PMID- 2908983 TI - Metastatic lung cancer in a young marijuana smoker. PMID- 2908984 TI - Toddler eats clonidine patch and nearly quits smoking for life. PMID- 2908985 TI - The effect of smoking on lactation and infantile colic. PMID- 2908986 TI - Are heavy smokers different from light smokers? PMID- 2908987 TI - Toward smoke-free VA hospitals. PMID- 2908988 TI - Warnings: smokers opt for the new, prefer carbon monoxide poisoning to fetal injury. PMID- 2908989 TI - Chain-chewin'. PMID- 2908991 TI - Cochlear implants are a contraindication to MRI. PMID- 2908990 TI - The warnings on cigarette packages are ineffective. PMID- 2908992 TI - One of at least three of a kind. PMID- 2908993 TI - Stuttering. PMID- 2908994 TI - Trends in cigarette smoking in the United States. The changing influence of gender and race. AB - Trends in the prevalence, initiation, and cessation of cigarette smoking are reported for the US population using weighted and age-standardized data from seven National Health Interview Surveys (1974 to 1985). The decline in prevalence was linear, with the prevalence for men decreasing at 0.91 percentage points per year to 33.5% in 1985 and the prevalence for women decreasing at 0.33 percentage points per year to 27.6% in 1985. For whites the rate of decline (percentage points per year) was 0.57, to 29.4% in 1985, and for blacks the decline was 0.67, to 35.6% in 1985. Smoking cessation increased among all gender-race groups from 1974 to 1985, with the yearly rate of increase (in percentage points per year) about equivalent for blacks (0.75) and whites (0.77), while it was higher in women (0.90) than in men (0.67). Smoking initiation decreased among young men ( 1.03), while it remained about the same in young women (+0.11). Initiation decreased at a more rapid rate in blacks (-1.02) than in whites (-0.35). We conclude that smoking prevalence is decreasing across all race-gender groups, although at a slower rate for women than men, and that differences in initiation, more than cessation, are primarily responsible for the converging of smoking prevalence rates among men and women. PMID- 2908995 TI - Trends in cigarette smoking in the United States. Educational differences are increasing. AB - National trends in smoking prevalence by educational category from 1974 through 1985 show that education has replaced gender as the major sociodemographic predictor of smoking status. Smoking prevalence has declined across all educational groups but the decline has occurred five times faster among the higher educated compared with the less educated. From 1974 to 1985, smoking prevalence among persons with less than a high school diploma declined to 34.2% (0.19 percentage points per year) whereas prevalence for persons with four years or more of college education declined to 18.4% (0.91 percentage points per year). Smoking cessation activity increased across all educational groups, but the rate of increase among the higher educated was twice that of lower-educated groups. Initiation of smoking among more-educated men decreased rapidly to 15% in 1985 but leveled off by 1987. Until 1985, less-educated young females were the only group in which smoking initiation was increasing. However, in 1987 a sudden and large decline in initiation among less-educated females occurred. The apparent recent changes in initiation patterns by educational level suggest that the converging of smoking prevalence between the genders may not continue. The large and widening educational gap in smoking suggests that health promotion priorities need to be reassessed. PMID- 2908996 TI - Trends in cigarette smoking in the United States. Projections to the year 2000. AB - Data from National Health Interview Surveys from 1974 through 1985 are used to project cigarette smoking prevalence to the year 2000. Smoking prevalence in the United States has declined at a linear rate since 1974. If this trend continues, in the year 2000, 22% of the adult population (40 million Americans) will be smokers. By the year 2000, the major inequalities in prevalence will occur among educational categories. At least 30% of those who have not proceeded beyond a high school education will be smokers, whereas less than 10% of college graduates will smoke. Among the other sociodemographic subgroups, smoking prevalence is expected to decrease by the year 2000 to 20% among men, to 23% among women, to 25% among blacks, and to 21% among whites. Between 1974 and 1985, approximately 1.3 million persons per year became former smokers, indicating considerable success in public health efforts to encourage people to stop smoking. However, in the early 1980s, approximately 1 million new young persons per year were recruited to the ranks of regular smokers. This is equivalent to about 3000 new smokers each day. Public health efforts need to focus more on preventing young people from starting to smoke, and such prevention efforts should particularly target less educated socioeconomic groups. PMID- 2908997 TI - Birth cohort analysis of prevalence of cigarette smoking among Hispanics in the United States. AB - To investigate historical trends of cigarette smoking among Mexican-Americans, Cuban-Americans, and Puerto Rican-Americans, we conducted a birth cohort analysis of smoking prevalence by using smoking histories of 8286 adults and adolescents from the 1982-1983 Hispanic Health and Nutrition Examination Survey. We constructed smoking prevalence curves for men and women among successive ten-year birth cohorts. Birth cohort-specific prevalence rates were higher for men than for women. Rates, however, decreased among successive cohorts of men. Conversely, rates increased among successive cohorts of Cuban-American and Puerto Rican American women. For example, peak rates among the 1911 through 1920 cohorts were 26% (Cuban-American women) and 25% (Puerto Rican-American women) compared with peak rates of 43% and 52%, respectively, among comparable groups from 1951 through 1960. These results demonstrate that despite a reduction of cigarette smoking among successive cohorts of Hispanic men, Hispanic women have made little progress or have actually increased their cigarette smoking. PMID- 2908998 TI - Comparing the prevalence of smoking in pregnant and nonpregnant women, 1985 to 1986. AB - The 1990 health objectives for the nation state that pregnant women should be only half as likely to smoke as nonpregnant women. To assess progress toward meeting this objective, we used cross-sectional data from the 26 states in the Behavioral Risk Factor Surveillance System in 1985 and 1986. We compared the prevalence of self-reported smoking among pregnant (N = 836) and nonpregnant (N = 18,025) women aged 18 to 45 years. Overall, pregnant women were 70% as likely to be current smokers as nonpregnant women (prevalence ratio, 0.7; 95% confidence interval, 0.6 to 0.8), while blacks showed the largest pregnancy-associated reduction in the prevalence of smoking (prevalence ratio, 0.5; 95% confidence interval, 0.3 to 0.9). Most of the difference in smoking prevalence occurred not because pregnant women were less likely to have ever smoked, but because pregnant women were more likely to have quit smoking than nonpregnant women. However, unmarried pregnant white women were 40% more likely to smoke than their nonpregnant counterparts (prevalence ratio, 1.4; 95% confidence interval, 1.1 to 1.7). We conclude from this analysis that the 1990 health objective for smoking among pregnant women is unlikely to be achieved. Clinicians providing care to pregnant women need to pay increased attention to smoking cessation. PMID- 2908999 TI - Reducing the illegal sale of cigarettes to minors. AB - This study reports on an effort to stop the illegal sale of cigarettes to minors. In Santa Clara County, Calif, 412 stores and 30 vending machines were visited by 18 minors aged 14 through 16 years with the intent to purchase cigarettes; they were successful at 74% of the stores and 100% of the vending machines. After an aggressive six-month campaign using communitywide media, direct merchant education, contact with the chief executive officers of chain stores and franchise operations owned by major companies, and grassroots work with community organizations, the percentage of stores with illegal over-the-counter sale of cigarettes to minors was reduced to 39%. Sales from vending machines were not reduced. While much remains to be accomplished in stopping the illegal sale of tobacco to minors, data from this study illustrate that a well-designed community and merchant education campaign can significantly reduce such sales. PMID- 2909000 TI - Recall and eye tracking study of adolescents viewing tobacco advertisements. AB - The warning on tobacco advertisements was required by the federal government, presumably as a health message to educate the public about the risks associated with tobacco use. Despite its potential public health role, there have been few published studies on the effectiveness of these warnings as a health message. The present study used well-accepted market research methods to examine adolescent viewing of tobacco advertisements. Sixty-one adolescents participated in the study. Eye tracking was used to study how participants viewed five different tobacco advertisements. The average viewing time of the warning amounted to only 8% of the total advertisement viewing time. In 43.6% of cases, the warning was not viewed at all. Following the advertisement viewing, participants were asked to identify the observed warnings within a list that included other simulated warnings. Subjects did only slightly better than random guessing in this test of recognition. Using market research criteria, the federally mandated warning must be viewed as an ineffective public health message in so far as adolescents are concerned. PMID- 2909001 TI - The Surgeon General's warnings in outdoor cigarette advertising. Are they readable? AB - Outdoor advertising media represent a major vehicle by which cigarette companies promote their products. We investigated the readability of the Surgeon General's warning in cigarette advertisements (ads) in two outdoor media: billboards and taxicab ads. In an experiment in metropolitan Atlanta under typical driving conditions, observers were able to read the entire health warning on 18 (46%) of 39 street billboards but on only two (5%) of 39 highway billboards. In contrast, the content of the ads (ie, brand name, other wording, and notable imagery) could be recognized under the same conditions on more than 95% of the billboards. In a similar study of 100 taxicab cigarette ads in New York City, observers were unable to read the health warning in any of the ads but were able to identify the brand name in all ads and notable imagery in 95% of the ads. Significant differences between the readability of the warning and identification of the advertising content persisted even when partially read warnings were considered to have been read. We conclude that the Surgeon General's warning is not readable in its current form in the vast majority of billboard and taxicab ads. Factors contributing to unreadability include the small size of the letters, the excessive length of the warnings, the distance between the viewers and the ads, and movement between the viewers and the ads. PMID- 2909003 TI - The silver anniversary. PMID- 2909002 TI - The making of a smoke-free medical center. AB - The concept of smoke-free medical facilities is in its formative stages, and such policies have received broad support. Although smoking has been restricted at Mayo Medical Center for many years, in 1986 it was decided that the medical center should become smoke free. This report summarizes the methods used in developing and implementing a smoke-free policy. This experience suggests that with proper planning, the implementation can be smooth. The message being given to patients and staff concerning the health risk of smoking is now more consistent, and there has been wide acceptance of the policy by staff and patients. It is concluded that such a policy can be effectively implemented, if it is well planned and supported. PMID- 2909004 TI - Routing a modern Pied Piper of Hamelin. PMID- 2909005 TI - Minority physician training: critical for improving overall health of nation. PMID- 2909006 TI - Preventing twists, turns on road to medical education from becoming permanent detours. PMID- 2909007 TI - Health educators turn to black community's leaders, organizations, other strengths. PMID- 2909008 TI - Research seeks to reduce toll of hypertension, other cardiovascular diseases in black population. PMID- 2909009 TI - From the Assistant Secretary for Health. PMID- 2909010 TI - From the Health Resources and Services Administration. PMID- 2909011 TI - Leads from the MMWR. Distribution of AIDS cases, by racial/ethnic group and exposure category, United States, June 1, 1981-July 4, 1988. PMID- 2909012 TI - Leads from the MMWR. Years of potential life lost due to cancer--United States, 1968-1985. PMID- 2909013 TI - Leads from the MMWR. Differences in death rates due to injury among blacks and whites, 1984. PMID- 2909014 TI - Pesticide residue in lanolin. PMID- 2909015 TI - Patients' and families' preferences for medical intensive care. PMID- 2909016 TI - Comparison of critical care by family physicians and general internists. PMID- 2909017 TI - Passionate kissing and microlesions of the oral mucosa: possible role in AIDS transmission. PMID- 2909018 TI - Susceptibility to influenza A in HIV-positive patients. PMID- 2909019 TI - Sliding injuries: the third base coach as prophylactic. PMID- 2909020 TI - The availability of proguanil for overseas travelers. PMID- 2909021 TI - Man-made death. PMID- 2909022 TI - Juvenile glaucoma, race, and refraction. AB - Of 68 patients who presented between the ages of 10 and 35 years with elevated intraocular pressure, 25 were classified as juvenile ocular hypertension and 43 as juvenile primary open-angle glaucoma. Blacks constituted a greater proportion of the primary open-angle glaucoma patients (47%) than of the ocular hypertensives (20%) and in both groups presented at younger ages than did whites. Myopia was present in 59% of the ocular hypertensives and 73% of the primary open angle glaucoma patients, of whom 39% had more than 6 diopters of myopia. All eyes of black patients with more than 3 diopters of myopia had glaucomatous defects compared with 52% of such eyes of white patients. Our data suggest that myopia is strongly associated with juvenile open-angle glaucoma and that young black patients with elevated intraocular pressure, especially when myopic, are more susceptible to glaucomatous damage than are whites. PMID- 2909024 TI - Representation of American blacks in clinical trials of new drugs. AB - Investigations that have revealed racial differences in drug response and disposition indicate the need for adequate representation of racial minorities in clinical drug trials. There is concern, however, that there may be a disproportionate use of racial and ethnic minorities in clinical research due to the inner city location of most university hospitals. To examine this issue, we reviewed the representation of American blacks in 50 recently published clinical trials of new drugs. This survey revealed that investigators do not seem to adequately take into account racial differences as a potential source of variability. It also was found that in the majority of studies, the proportion of black subjects is less than their proportion in the general population. This underrepresentation in clinical trials suggests that insufficient data exist to accurately assess the safety and efficacy of many new drugs in American blacks. PMID- 2909023 TI - HIV screening and counseling for intravenous drug abuse patients. Staff and patient attitudes. AB - At least one third of patients enrolled in a methadone maintenance treatment program are willing to comply voluntarily with screening for and counseling about human immunodeficiency virus (HIV). A questionnaire about knowledge, attitudes, and behavior concerning acquired immunodeficiency syndrome was answered anonymously by 79% (46) of the clinical staff and 67% (868) of the enrolled patients. On their own initiative, 21% of the patients had already received voluntary anonymous HIV screening and brief counseling, seldom discussing the result with the staff. Approximately 90% of the staff and a majority of the patients (72%) thought a voluntary HIV screening program should be offered to all patients. Almost all staff (98%), but only 50% of the patients, felt the HIV test results should be known to physicians, nurses, and counselors at the clinic. Few staff members (15%) believed that patients had changed their sex behavior; more (48%) felt that needle sharing was reduced. Patients believed methadone patients in general had changed their sex behavior (49.2%) and reduced needle sharing (62%) to prevent becoming infected. Patients reported statistically significant reductions both in number of sex partners and in personal needle sharing during the past year. PMID- 2909025 TI - Black student enrollment in US medical schools. AB - Blacks represent about 12% of the nation's population, but only 6% of the total medical school enrollment, 5% of medical school graduates, 5% of postgraduate trainees, 3% of physicians in practice, and 2% of medical school faculties. Addressing this underrepresentation of blacks in medicine not only is a matter of justice, equity, and national conscience but also has implications for the provision of quality physician care to this nation's minority and medically underserved populations. Black physicians are more likely to understand the cultural and social context of illness and disability among blacks and are also more likely to be able to communicate effectively with black patients. Black physicians are also more likely to practice in communities whose residents lack adequate access to medical care. An approach to addressing the problem of underrepresentation is proposed, consisting of activities at the precollege, college, and medical school levels. PMID- 2909026 TI - Access to medical care for black and white Americans. A matter of continuing concern. AB - A 1986 national survey of use of health services shows a significant deficit in access to health care among black compared with white Americans. This gap was experienced by all income levels of black Americans. In addition, the study points to significant underuse by blacks of needed medical care. Moreover, blacks compared with whites are less likely to be satisfied with the qualitative ways their physicians treat them when they are ill, more dissatisfied with the care they receive when hospitalized, and more likely to believe that the duration of their hospitalizations is too short. PMID- 2909027 TI - Glaucoma in blacks: where do we go from here? PMID- 2909028 TI - Community empowerment as a strategy for health promotion for black and other minority populations. PMID- 2909029 TI - Old bedfellows: ethics and obstetrics and gynecology. PMID- 2909030 TI - The relationship of one abnormal glucose tolerance test value and pregnancy complications. AB - While an abnormal oral glucose tolerance test (GTT) is known to be associated with an increased risk of pregnancy complications, the impact of one abnormal value is not clear. In 1986 we screened 4618 pregnant women for gestational diabetes at 24-28 weeks' gestation. Eighty-seven percent had normal results; of the 13% with abnormal screening tests, 139 had one abnormal value on the subsequent 3-hour oral GTT. These women were then compared with 725 randomly selected patients with a normal screening test. The frequency of chronic hypertension, cesarean section, 5-minute Apgar score below 7, preterm delivery, shoulder dystocia, congenital malformations, and perinatal mortality did not differ significantly between the groups. The incidence of macrosomia (birth weight above 4000 g) was significantly greater in the study group (18.0%) than in the control group (6.6%) (odds ratio 2.18; 95% confidence interval 1.77-5.37), a relationship that persisted after controlling for confounding risk factors by logistic regression modeling (odds ratio 2.55; 95% confidence interval 1.44 4.52). The incidence of preeclampsia/eclampsia was significantly greater in the study group (7.9%) than in the control group (3.3%) (odds ratio 2.51; 95% confidence interval 1.14-5.52), which also persisted after controlling for confounding risk factors using logistic regression modeling (odds ratio 2.81; 95% confidence interval 1.26-6.28). Our results suggest that patients with one abnormal value on an oral GTT during pregnancy are at risk for delivering macrosomic infants and developing preeclampsia/eclampsia. PMID- 2909031 TI - The effect of mode of delivery on the risk of intraventricular hemorrhage in nondiscordant twin gestations under 1500 g. AB - The effect of birth order, presentation, and mode of delivery on neonatal outcome in nondiscordant twin gestations under 1500 g was investigated. All neonates had echoencephalograms performed by the fourth day of life to diagnose the presence and severity of intraventricular hemorrhage. One hundred fifty-six sets of twins were included in the study, of which 59 were in a vertex/vertex presentation, 59 in vertex/nonvertex presentation, and 38 with twin A in a nonvertex presentation. Second twins were characterized by a higher incidence of respiratory distress syndrome (RDS): 66 versus 54% (P less than .05), and severe grades of intraventricular hemorrhage: 30 versus 19% (P less than .01). For vertex/vertex twins, cesarean delivery did not result in improved outcome. Rather, the incidence of RDS was significantly increased in neonates from this group delivered by cesarean birth: 67 versus 46% (P less than .01). Among twins in which at least one of the fetuses was in a nonvertex presentation, those born via cesarean delivery demonstrated a lower incidence of both severe grades of intraventricular hemorrhage and mortality. However, after multivariate analysis to correct for differences in birth weight between the groups, no advantage for cesarean delivery could be demonstrated. Therefore, differences in birth weight, rather than in mode of delivery, accounted for the differences in the neonatal outcome of nonvertex-presenting twins. PMID- 2909032 TI - Educating the obstetrician-gynecologist for the future. AB - Among the many factors that have altered the practice of obstetrics-gynecology are the following: the numbers of obstetrician-gynecologists, the increasing percentage of women entering the specialty, the expansion of ambulatory services with a simultaneous reduction in hospital admissions, a decrease in gynecologic surgical procedures, a stabilized number of total births with an anticipated increase in those to socially deprived and unmarried women, an increasing number of elderly women, general social and behavioral changes, and increasing outside control of practice. A proposal is presented for improving the education of residents and obstetrician-gynecologists in practice. PMID- 2909033 TI - Guidelines for assessment and treatment of sexual dysfunction. AB - This article presents a diagnostic and treatment planning guide that can be used when a patient complains of a sexual problem. The basic principles are summarized in the form of a grid. The axes of the grid represent "problem focus" and "influencing variables." The grid can be used to aid in diagnosis, to assess the severity of a sexual problem, to suggest a direction for treatment, and to guide referral. PMID- 2909034 TI - Methadone maintenance in pregnancy: consequences to care and outcome. PMID- 2909035 TI - Peritoneal cytology as an indicator of disease in patients with residual ovarian carcinoma. PMID- 2909036 TI - Management of genital herpes infection in pregnancy. PMID- 2909038 TI - Karyotypes of 1142 couples with recurrent abortion. PMID- 2909037 TI - The role of infection in the etiology of preterm birth. PMID- 2909039 TI - Malpractice--the syndrome of the 80s. PMID- 2909040 TI - Hysteroscopy with selective endometrial sampling compared with D&C for abnormal uterine bleeding: the value of a negative hysteroscopic view. AB - Hysteroscopic evaluation of 187 patients with abnormal uterine bleeding is reviewed. One hundred fifty-one patients had recent tissue sampling by a blind method. The hysteroscope with selected endometrial sampling was more accurate in 9.1% and less accurate in only 0.5% of patients. The specificity of both techniques with selected biopsies was 100%, but the sensitivity of hysteroscopy was greater (98%) than that of D&C (65%). Endometritis was the only condition missed by hysteroscopic viewing and selected biopsy. Those lesions missed by blind tissue sampling were uterine fibroids and endometrial polyps. Among 91 patients whose hysteroscopic view was negative, an abnormality was identified by tissue sampling in only one patient with endometritis. PMID- 2909041 TI - The clinical significance of pain and cognitive activity in latent labor. AB - We examined the relationship between pain and cognitive activity during the latent (less than or equal to 3 cm), mid-active (5-7 cm), and transition (greater than or equal to 8 cm) phases of labor and the concomitant efficiency of the latent, active, and descent phases in 115 nulliparous women. Patients provided subjective pain ratings and described their thoughts during each of the three phases. Higher levels of pain during the latent phase of labor were predictive of longer latent (r = 0.58) and active (r = 0.50) phases of labor. Distress-related thoughts during latent labor were predictive of longer latent (r = 0.31, P less than .01), active (r = 0.67), and second-stage (r = 0.61) labor. We found no relationships between pain and cognitive activity measured during active labor and efficiency of active labor or second stage of labor. Pain and cognitive activity assessed during the latent phase were also prognostic of obstetric outcome. Thirteen of 19 women (68.4%) who reported "horrible" or "excruciating" pain required instrumental delivery, compared with eight of 27 women (29.6%) in the "discomforting" pain group. Subjects in the "distress-related" cognitive group had 2.6 times the incidence of instrumental delivery, five times the incidence of abnormal fetal heart rate patterns, and four times the requirement for pediatric assistance for the neonate than subjects in the "coping" group. We conclude that latent labor is a critical phase in the psychobiology of labor and that pain and cognitive activity during this phase are important contributors to labor efficiency and obstetric outcome. PMID- 2909042 TI - Management of coexistent stress and urge urinary incontinence. AB - Fifty-two patients with objective evidence of pressure equalization incontinence and detrusor instability were evaluated retrospectively to compare nonsurgical modes of therapy with retropubic surgery. Based on the patient's desire for surgery and her overall medical condition, 27 women were treated primarily with retropubic urethropexy (modified Burch procedure) and 25 with various combinations of oxybutynin, imipramine, and estrogen. Thirty-two percent of the patients treated medically were cured and 28% were markedly improved, whereas 59% of patients treated surgically were cured and 22% improved. There was no statistically significant difference in the results between medical and surgical therapy. All failures in the surgically treated group were due to persistent detrusor instability after surgery. We identified no preoperative urodynamic criteria that consistently and accurately predicted surgical outcome in patients with combined stress and urge incontinence. Patients with combined stress incontinence and detrusor instability should initially be managed medically, as this will reduce the incidence of surgical intervention. PMID- 2909043 TI - Effect of dietary protein on glomerular filtration rate in pregnancy. AB - High dietary protein intake is known to increase glomerular filtration rate in the nonpregnant state. The effects of dietary protein on renal function in human pregnancy are not well known. We studied 392 patients with singleton uncomplicated pregnancies at gestational ages of 7-40 weeks. Creatinine clearance was correlated with protein intake estimated from 24-hour dietary recall during the same period. Creatinine clearances were significantly higher when dietary protein was more than 50 g than when it was less than 50 g (P less than .005). The short- or long-term significance of this finding is unclear. PMID- 2909044 TI - Inhibition of ovarian cancer cell proliferation in vivo and incorporation of 3H thymidine in vitro after follicle regulatory protein administration. AB - Follicle regulatory protein immunoreactivity and biologic activity were measured in ascites from a patient with juvenile granulosa cell tumor. Microscopic examination of immunohistochemical staining of a juvenile granulosa cell tumor with anti-follicle regulatory protein antisera showed homogeneous cytosolic expression of follicle regulatory protein throughout the tumor. Tumor cells were injected subcutaneously into nude mice. Partially purified follicle regulatory protein (50 micrograms/day) was then injected daily for 10 days, or for 25 days once the tumor became palpable. Treatment with follicle regulatory protein significantly slowed the rate of tumor growth with both treatments. To test the tissue specificity of the effect, a metastatic, well-differentiated endometrial adenocarcinoma was also grown in nude mice. Follicle regulatory protein treatment did not alter the rate of tumor growth. An in vitro clonigenic assay confirmed these in vivo results. Partially purified follicle regulatory protein had a biphasic effect on the proliferation of juvenile granulosa tumor cell but did not affect the proliferation of endometrial adenocarcinoma cells. Clonigenic assays were performed on five ovarian adenocarcinomas passaged in vitro, and these tumor cells exhibited a biphasic response to follicle regulatory protein. Immunoneutralization studies showed that this biphasic response was due to impurities in the follicle regulatory protein preparations. The longer the exposure of the tumor cells to follicle regulatory protein, the greater the degree of inhibition of proliferation. In summary, administration of follicle regulatory protein slowed tumor growth through a direct effect on the tumor cell rather than an indirect effect on the hormonal or immune status of the host. PMID- 2909045 TI - Sialyl Lewis-Xi antigen in patients with gynecologic tumors. AB - Sialyl Lewis-Xi antigen was measured by sandwich radioimmunoassay in sera from patients with various gynecologic tumors: 27 uterine myomas, 117 cervical cancers, 46 endometrial cancers, 54 benign ovarian cysts, and 47 ovarian cancers. Among the patients with uterine malignancies, only a few cases showed serum sialyl Lewis-Xi antigen values in excess of the cutoff limit. On the other hand, among the patients with ovarian cancers, serum sialyl Lewis-Xi antigen was elevated significantly in the following order: clinical stage I (44%), stage II (50%), and stage III (62%). The antigen level also correlated with the effect of treatment. However, serum sialyl Lewis-Xi antigen was elevated in 9% of patients with benign ovarian cysts and in 1.4% of normal volunteers. The lack of tumor specificity of sialyl Lewis-Xi antigen limits its diagnostic value for gynecologic malignancies, but serial measurement of this antigen may be useful in evaluating therapy and monitoring patients. PMID- 2909046 TI - Serum albumin reserve for bilirubin binding during pregnancy in healthy women. AB - The concentrations of serum albumin and albumin reserve for bilirubin binding were studied in 24 healthy women during and after pregnancy, using monoacetyl 4,4'-diamino-diphenylsulphone as a deputy ligand for bilirubin. In the first trimester, the serum albumin concentration was already diminished. Likewise, the serum reserve albumin for bilirubin binding was reduced gradually during pregnancy. These reductions were evident as early as the 20th week of gestation, and at delivery the level averaged 53% of the nonpregnant level. The reduction in bilirubin binding capacity was partly dependent on the decreasing serum albumin concentration, but a reduction in the albumin molecule's binding capability was also shown. This binding defect, which is also present in neonates, is not fully explained. The reduction in bilirubin binding capability probably reflects a reduced degree of protein binding for many protein-bound drugs during pregnancy, which may contribute to pharmacokinetic alterations in pregnancy. PMID- 2909047 TI - Disseminated intravascular coagulation and the syndrome of hemolysis, elevated liver enzymes, and low platelets in severe preeclampsia. AB - To clarify the role of disseminated intravascular coagulation (DIC) in women with the hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome, serial coagulation studies were performed prospectively in 18 patients. A semiquantitative DIC scoring system was used retrospectively to augment the diagnostic confidence of coagulopathy. At the time of admission to the hospital, three patients showed no evidence of DIC, eight had suspected DIC, and seven had manifest DIC. The intravascular coagulation process was progressive in all patients; upon delivery, eight patients proved to have suspected DIC and ten had manifest DIC. The laboratory criteria of DIC were found to agree with the degree of organ dysfunction. Patients with manifest DIC at delivery developed significantly more life-threatening maternal complications than did patients with suspected DIC (P less than .02). Conservative management was not possible in any patients who were admitted with overt DIC because of deterioration of maternal and fetal status. Application of a sensitive DIC scoring system may be valuable in managing patients with the HELLP syndrome and selecting patients who may be treated expectantly. PMID- 2909048 TI - Anatomy of the nasolabial fold: the keystone of the smiling mechanism. AB - The nasolabial fold is absent in the face of the newborn, disappears in the paralyzed face, but is retained in the face upon death. There is very little information in the literature on what makes up the fold. Four fresh cadavers were studied by taking a strip of facial tissue from each at right angles to the fold; all soft tissue layers through the face were included. Microscopic studies of the strips showed the fold to be made up of (1) dense fibrous tissue, (2) muscle fibers branching from the levator muscles of the upper lip, and (3) striated muscle bundles originating in the fold fascia. The studies also revealed the lip elevator muscles and the "fold muscles" coursing down the lip to traverse the orbicularis oris and insert into the dermis of the upper lip, the cutaneous vermilion junction, and vermilion. The smile is formed in stages, the first stage raising the lip to the fold by the levator muscles and the muscle bundles originating in the fold. The lip meets resistance at the fold because of cheek fat. The second stage involves the raising of the lip and fold upward by the levator muscles of the upper lip. Clinically, this study relates to reanimating the paralyzed face. PMID- 2909049 TI - Extensor digitorum brevis as an island flap in the reconstruction of soft-tissue defects in the lower limb. AB - The extensor digitorum brevis island flap is a versatile and robust flap able to provide adequate bulk and coverage in soft-tissue defects of the lower limb. The donor-site deformity is limited to the necessary scar needed to approach and rotate the muscle. An anatomic study was performed in 10 fresh cadavers and consisted of two parts: study of the muscle flap itself, and examination of skin vascularization. Methylene blue and Salmon's mass (radiopaque) were injected through the three main arteries of the leg. Muscle and cutaneous staining were noted. Clinical applications of this flap are reported. These resulted in successful healing of the defect with good aesthetic and functional results on both recipient and donor sites. Long-term follow-up was maintained for up to 21 months. PMID- 2909050 TI - The retaining ligaments of the cheek. AB - The zygomatic ligaments (McGregor's patch) anchor the skin of the cheek to the inferior border of the zygoma just posterior to the origin of the zygomaticus minor muscle. The mandibular ligaments tether the overlying skin to the anterior mandible. Both these ligaments are obstacles to surgical maneuvers intended to advance the overlying skin. They also restrain the facial skin against gravitational changes, and they delineate the anterior border of the "jowl" area. The platysma-auricular ligament is a thin fascial sheet that extends from the posterosuperior border of the platysma and that is intimately attached to the periauricular skin; it serves as a surgical guide to the posterosuperior border of the platysma. The anterior platysma-cutaneous ligaments are variable fascial condensations that anchor the SMAS and platysma to the dermis. They can cause anatomic disorientation with dissection of false planes into the dermis. These four ligaments are useful as anatomic landmarks during facial dissections. The tethering effects of the zygomatic and mandibular ligaments must be interrupted if a maximum upward movement of the facial skin is desired. PMID- 2909051 TI - Fasciocutaneous flaps: an experimental model in the pig. AB - No experimental studies have substantiated the claim that fasciocutaneous flaps are superior to skin flaps. Using fasciocutaneous flaps designed in the pig, both flap survival and blood flow were assessed. The forelimb and hindlimb fasciocutaneous flaps survived to 8.2 +/- 0.3 cm and 7.9 +/- 0.3 cm, respectively, compared with 7.3 +/- 0.3 cm and 6.7 +/- 0.3 cm for the comparable cutaneous flaps, a statistically significant finding (p less than 0.01). Random fasciocutaneous flaps survive 12 to 18 percent longer than skin flaps. Using the radioactive microsphere technique, blood flow was measured after flap elevation, and flap survival was estimated using fluorescein. Again, a significant difference in flap survival was found, but there was no significant difference in measured blood flow. This can be explained by the relatively large interval between blood flow measurements (2 cm) compared with the observed difference in survival length (1.0 +/- 0.3 cm). PMID- 2909052 TI - The effect of systemic isotretinoin on wound contraction in guinea pigs. AB - An experimental study was designed using Hartley guinea pigs to evaluate wound contraction on animals receiving systemic isotretinoin at a dose of 10 mg/kg. Half the animals received isotretinoin for 4 weeks before the surgery and for 2 weeks after the surgical procedure. A square of skin and panniculus carnosus measuring 200 mm2 was excised from the back of each animal, and the amount of wound contraction was determined by a computer program from the drawings on celluloid overlays done weekly. The animals on systemic isotretinoin had a significant delay in wound contraction when compared to control animals (p less than 0.001). When the medication was discontinued, all the animals had complete wound healing within a week. PMID- 2909053 TI - Effects of unrestricted motion on healing: a study of posttraumatic adhesions in primate tendons. AB - The effects of unrestricted motion on the surfaces of injured, healing tissue are largely speculative. To study this phenomenon, a new model employing 54 primate tendons and stereomorphometric image analysis was used to quantitate adhesion volume after a standardized surface injury. Three randomized groups (n = 18 per group) were studied: group I, incision/resection; group II, incision/resection plus ischemia; and group III, ischemia alone. The moving surfaces were observed at intervals from 1 week to 2 1/2 years using dissecting, light, and scanning electron microscopy. Fibroblasts were found to invade the traumatized segment from sources both intrinsic and extrinsic to the tendon, generating adhesive bands whose volume correlated with the degree of initial injury. The defect was ultimately effaced by scar, yet the continuous motion appeared to modify the healing by lengthening adhesive elements and by establishing a smooth, functional "neosheath" that coalesced from the overlying soft tissues. This proliferative response occurred in all specimens, peaked during the third week, and limited normal motion in only 12 percent. This model, the first to successfully study such surfaces in primates, also indicates that closure of the tendon sheath is unnecessary. PMID- 2909054 TI - Functional evaluation of complete sciatic, peroneal, and posterior tibial nerve lesions in the rat. AB - Quantification of peripheral nerve regeneration in animal studies of nerve injury and repair by histologic, morphologic, and electrophysiologic parameters has been controversial because such studies may not necessarily correlate with actual nerve function. This study modifies the previously described sciatic functional index (SFI), tibial functional index (TFI), and peroneal functional index (PFI) based on multiple linear regression analysis of factors derived from measurements of walking tracks in rats with defined nerve injuries. The factors that contributed to these formulas were print-length factor (PLF), toe-spread factor (TSF), and intermediary toe-spread factor (ITF). It was shown that animals with selective nerve injuries gave walking tracks that were consistent, predictable, and based on known neuromuscular deficits. The new formula for sciatic functional index was compared with previously described indices. The sciatic functional index, tibial functional index, and peroneal functional index offer the peripheral nerve investigator a noninvasive quantitative assessment of hindlimb motor function in the rat with selective hindlimb nerve injury. PMID- 2909055 TI - Cosmetic surgery: a theological comment. PMID- 2909056 TI - Bilateral thymus found in association with unilateral cleft lip and palate. AB - Ectopic localizations of the thymus have been reported in a variety of unusual sites, but not on the surface of the skin of the neck. As one can see in our case, the left neck mass (1.5 x 2 x 0.5 cm) and the right neck mass (4 x 4 x 0.5 cm), when added together in weight, also equal the total weight of the thymus at birth. Also, not being able to encounter the "sail sign" of the thymus gland on the chest x-ray proved to us that no other thymus gland was present. Because of these unusual findings, prior to excision of any congenital lesion in the neck, a biopsy should be done, and only after that should one proceed with the necessary surgical intervention. We are presenting this case because it is unique in this category. PMID- 2909057 TI - Primary nonmicrosurgical reconstruction following ear avulsion using the temporoparietal fascial island flap. AB - Primary ear reconstruction following avulsion using a temporoparietal fascial island flap based on the superficial temporal vessels is presented as a modification of an existing technique for the acute treatment of this difficult problem, offering a further alternative to established traditional nonmicrosurgical procedures. PMID- 2909058 TI - Carotid thrombosis following surgical release of temporomandibular ankylosis. AB - Temporomandibular ankylosis frequently involves massive bony proliferation which can approach the carotid artery at the base of the skull. During the resection of the bony ankylosis, the artery can be injured. The first such case is reported which led to a thrombosis and hemispheric stroke. PMID- 2909059 TI - Facial burns as a complication of office surgery lighting. AB - Three patients underwent rhytidoplasty in an office surgical facility under dual ceiling-mounted lights. Each patient incurred a third-degree burn on the left cheek. A particular combination of a specific defective light fixture and bulb appeared to be the causative factor. The risk of burning human tissue is enhanced when epinephrine is injected for vasoconstriction and the tissue is undermined. In addition, focusing dual lights on the surgical field increases the radiant energy delivered. The maximum radiant energy safe for human tissue should not exceed 25 mW/cm2. PMID- 2909060 TI - Surgical correction of Stahl's ear using the cartilage turnover and rotation method. AB - Various operative methods for the correction of Stahl's ear exist. We, however, have devised an alternative "turnover and rotation" procedure. In this procedure, the deformed cartilage itself is used in its original contour to form a new scaphoid fossa, thus simplifying the corrective procedure and establishing a reliable operative method in which reversion to the original state is thought to be highly unlikely. PMID- 2909061 TI - The bimanual examination for assessing instability in naso-orbitoethmoidal injuries. AB - A new technique is presented for examining patients suspected of having fractures in the naso-orbitoethmoidal region. It consists of a bimanual examination with a Kelly clamp intranasally and the opposite index finger externally. It has proven reliable in over 500 patient screenings to date. This technique is recommended as an addition to, and not a replacement for, the standard physical examination and radiologic evaluation of the maxillofacial trauma patient. PMID- 2909062 TI - A silicone template to facilitate cartilage grafting in the nose. AB - Silicone sheeting that has the thickness and consistency of septal cartilage for use as a template has been developed to facilitate cartilage grafting in the nose. This technique makes it easier to determine whether or not a graft will correct the deformity and how much autogenous material will be needed before the donor site is harvested. It also allows for more accuracy in the sizing and positioning of the grafts. PMID- 2909063 TI - Periosteal flaps and grafts in primary cleft repair: a follow-up study. AB - A long-term follow-up study of maxillary clefts operated on primarily with the maxillary periosteal flap (67 patients) and the free tibial periosteal graft (23 patients) showed a definite bone bridge in 64 versus 85 percent of the patients. Still, secondary bone grafting was indicated in both in over 70 percent. Lateral crossbite was observed in all and anterior crossbite (mostly dental) was seen in over 80 percent of both groups. There were no statistically significant differences in the cephalometric angular measurements between the groups. Inside the maxillary periosteal flap group the maxillary growth was more retarded in unilateral and especially bilateral complete clefts than in alveolar clefts only. The maxillary growth seemed to be on average better than in primarily bone grafted materials. The primary use of periosteum had been abandoned in our unit already in 1974, because it did not fulfill the expectations of prevention of maxillary collapse, lesser need for secondary bone grafting, and better midfacial growth. PMID- 2909064 TI - A convenient infant tourniquet. AB - A simple, readily available blood pressure cuff designed specifically for neonates, infants, and small children is recommended for use in hand surgery as a tourniquet. Most institutions that have pediatric medicine or surgical departments have these as stock, and thus the problem of illfitting standard cuffs can be avoided where a tourniquet is needed. PMID- 2909065 TI - Flash fluorometer made from off-the-shelf photographic equipment to measure tissue levels of fluorescein. AB - A device to measure fluorescein in tissue has been constructed from standard photographic equipment--an electronic strobe and a flashmeter both covered with interference filters. The instrument works well in the light and need not touch the area being measured, an advantage over existing fluorometers. The instrument has been used to measure the amount of dye in flaps in rats, pigs, and three humans. The results revealed that the amount of dye in a freshly made flap was rarely as much as in normal skin, and skin with less than 20 percent of the dye of control areas usually sloughed, although there were exceptions. In the future the instrument will be improved, and its readings will be compared to those obtained from radioactive microspheres, the present "gold standard" of techniques to measure vascularity. The instrument can be used to estimate the blood supply to any tissue and seems to be as reliable as the dermofluorometers already on the market. PMID- 2909066 TI - Aloe vera for burns. PMID- 2909067 TI - Aloe vera, salicylic acid, and aspirin for burns. PMID- 2909068 TI - Removing part of the dermis in reduction by the inferior pedicle technique. PMID- 2909069 TI - Periorbital myxedema. PMID- 2909070 TI - Liposuction cannula design problems. PMID- 2909071 TI - Intermaxillary fixation. PMID- 2909072 TI - Scleroderma after silicone augmentation mammaplasty: is there a causative relationship? PMID- 2909073 TI - Laser welding in microvascular surgery. PMID- 2909074 TI - Drain removal in the presence of a breast implant. PMID- 2909075 TI - Publication lag times in Plastic and Reconstructive Surgery. PMID- 2909076 TI - Repair of cleft lip with nonsurgical correction of nasal deformity in the early neonatal period. AB - Auricular cartilage is soft and plastic at birth, so that congenital auricular deformities can easily be corrected nonsurgically in the early neonatal period. However, as the infant grows older, the flexibility of the auricle decreases. Alar cartilage exhibits the same elasticity as auricular cartilage in the early neonate. When a cleft lip is repaired, typically when the infant is about 3 months of age, it becomes difficult to correct the nasal deformity without surgical intervention. However, based on our experience, there is a fair possibility of correcting the cleft lip nasal deformity with a nonsurgical procedure in the early neonatal period. We performed cleft lip repair accompanied by nonsurgical correction of the nasal deformity in 44 neonates aged 2 to 7 days. A special retainer was placed in the affected nostril for 3 months. Following observation of 31 infants for 12 months or longer, their nasal shapes and symmetry were considered superior to those conventionally operated on at about 3 months of age. Except for one nasal infection, there were no complications. PMID- 2909077 TI - An alternate strategy for reducing the large nasal base. AB - The position of the dorsum directly influences the apparent size of the nasal base: the higher the bridge, the smaller the nasal base seems. This powerful optical illusion provides the surgeon with an alternate strategy for creating harmony in the nose with a low, straight dorsum and a disproportionately large nasal base. Instead of reducing the lower nose, the surgeon can augment the upper nose (and make whatever nasal base changes are independently necessary). This alternate strategy limits the amount of nasal skeletal reduction necessary, thereby limiting the potential for postoperative change and soft-tissue distortion and directly increasing the surgeon's control over the result. PMID- 2909078 TI - En bloc cervical lipectomy for treatment of the problem neck in facial rejuvenation surgery. AB - The treatment of cervical fat in facial aesthetic surgery has received much attention in recent years. Suction lipectomy has become a very popular technique for removing cervical fat because it is easy to perform and results in few complications. This paper describes the en bloc excision of cervical fat in conjunction with rhytidectomy. The senior author has treated 1,000 patients over 17 years using this technique with a high degree of patient satisfaction and minimal morbidity. Although suction lipectomy alone may be indicated for the younger patient, our experience suggests that the en bloc excisional technique is the treatment of choice in the older patient in whom a rhytidectomy is also indicated. In contrast with suction lipectomy, we have found that the en bloc excision of cervical fat allows for more anatomic dissection and facilitates removal of greater amounts of fat and better redraping of the cervical skin. PMID- 2909079 TI - Surgical treatment of gynecomastia in the body builder. AB - The surgical correction of gynecomastia presents particular problems in the body builder who takes medical treatment of anabolic steroids. In 38 corrections, no fat suction was necessary and only an extensive surgical extirpation of the gland was performed. Superior cosmetic results were obtained with this treatment, with the only problem being increased bleeding in these patients who have very large chest-wall muscles and an enlarged circulation. PMID- 2909080 TI - Morphologic characterization of acute injury to vascular endothelium of skin after frostbite. AB - Cyclo-oxygenase inhibitors and free-radical scavengers protect the skin against necrosis induced by frostbite. However, the tissue component(s) that determine the evolution of skin necrosis and the mechanism of this pharmacologic protection are not precisely defined. We have studied freezing injury to rabbit ears by serial biopsies examined by light and electron microscopy. The morphologic evidence of skin injury due to freezing was localized exclusively in the endothelial cells, particularly in the arterioles. Within 1 hour, the entire microvasculature demonstrated endothelial damage. Intravascular platelet aggregation occurred just after thawing and closely paralleled the endothelial cell injury. Very few neutrophils were seen initially (at 10 minutes). By 1 hour, leukocyte aggregates were present, and they further increased at 6 hours. Swelling of the interstitium started 10 minutes after thawing, while extravasation of erythrocytes began to appear by 6 hours. Parenchymal elements of skin were relatively free of damage. In the ear cartilage, the chondrocytes showed evidence of damage immediately after freezing. The administration of superoxide dismutase (SOD) during thawing (reperfusion) did not qualitatively alter any of the initial morphologic changes induced by freezing. We conclude that the endothelial cell is the initial target of injury induced by freezing, an initial injury that is mediated by a non-free-radical-mediated mechanism. It is likely that this acute injury ultimately compromises blood flow and leads to skin necrosis. PMID- 2909081 TI - Salvage of jeopardized total-knee prosthesis: the role of the gastrocnemius muscle flap. AB - Total-knee arthroplasty has provided many patients with excellent long-term functional results. However, exposure of a total-knee replacement usually eventuates in failure. The relatively superficial location of the prosthesis, the need for early active motion, previous surgical incisions, and a variety of systemic factors may militate against early wound healing. Restoration of well vascularized soft-tissue cover can salvage an otherwise disastrous situation. The authors recommend early operative intervention upon observation of wound breakdown, devitalized skin edges, or significant subcutaneous infection leading to necrotic overlying skin. The operative procedure found to salvage the majority of prostheses consists of adequate debridement, antibiotic irrigation (of the joint, if exposed), and coverage with a well-vascularized muscle flap, preferably the medial gastrocnemius muscle. The operative technique and ultimate long-term outcome are reviewed based on experience with 10 consecutive patients presenting with a jeopardized knee prosthesis. Follow-up ranged from 1 to 6 years. Representative case histories are presented. PMID- 2909082 TI - Muscle-flap coverage of exposed endoprostheses. AB - A well-entrenched tenet in the orthopedic community is that dehiscent wounds overlying exposed endoprostheses should be treated by implant removal and delayed reconstruction. A new management protocol utilizing thorough soft-tissue debridement and myocutaneous or muscle-flap coverage was evaluated in four patients at the UCLA Medical Center who presented with exposed endoprostheses. These prostheses were placed for total-joint replacement or limb salvage surgery. All four prostheses and extremities were salvaged without the need for endoprosthesis removal or exchange, and no infections developed. The results suggest that late aseptic wound dehiscence with an exposed endoprosthesis need not be managed with prosthetic removal, arthrodesis, or amputation. This one stage procedure avoided infection, allowed early mobilization, and shortened hospitalization. PMID- 2909083 TI - Occult fractures of the proximal femur: MR imaging. AB - Coronal T1-weighted magnetic resonance (MR) images were obtained on a 1.5-T system in 23 patients in whom there was a high clinical suspicion of hip fracture although initial radiographs were normal. MR imaging correctly demonstrated fracture in nine of nine patients; the precise configuration of the fracture line was delineated in eight patients. MR imaging was useful in excluding fractures in 14 of 14 patients, who were subsequently followed up clinically for a minimum of 3 months. Radionuclide scans were positive in four of four patients with fractures and equivocal in one patient who was subsequently demonstrated to have no fracture. Additional imaging studies were requested by clinicians in all cases in which the bone scan was positive. The results of this study suggest that MR imaging can provide a rapid, cost-effective, and anatomically precise diagnosis of hip fracture in patients with normal or equivocal initial radiographs. The specificity of the diagnosis achieved can obviate supplemental imaging examinations, with their attendant additional expense and radiation exposure. PMID- 2909084 TI - MR imaging of the ankle: normal variants. AB - Thirty asymptomatic ankles were studied with high-resolution surface coil magnetic resonance (MR) imaging to identify normal structures. Several normal variants were demonstrated, including (a) Cortical irregularity of the posterior tibiotalar joint (should not be mistaken for osteonecrosis) in 27 of 30 cases; (b) normal posterior talofibular ligament with irregular and frayed superior edge simulating a tear in 13 of 30 cases; (c) normal navicular insertion of the posterior tibial tendon with heterogeneous signal intensity in 14 of 30 cases; (d) deltoid ligament inhomogeneity in seven of ten cases; and (e) fluid in the shared peroneal tendons sheath (may be confused with a longitudinal tendon tear) in three of 30 cases. Ankle imaging with the use of MR is still a relatively new procedure. Further investigation is needed to better define normal anatomy and normal variants. PMID- 2909085 TI - Quantitative dual-energy radiographic absorptiometry of the lumbar spine: in vivo comparison with dual-photon absorptiometry. AB - Quantitative dual-energy radiographic absorptiometry (DRA) and dual-photon absorptiometry (DPA) were compared to determine the best means of assessing bone density. Both methods were used to evaluate the lumbar spine in 107 women (aged 35-84 years [mean, 64 years]) referred for evaluation of osteoporosis risk. High correlation was documented between measurements derived by the two techniques, with a .95 linear regression coefficient for the total spine density measurement. Age-related regression equations were similar in slope but manifested different intercepts. Bone mineral density values derived with DRA were consistently lower than those obtained with DPA (conversion equation: DPA density = [1.067 X DRA density] + 0.163). Besides the inherent imperfections of each system, it was found that inaccurate identification of intervertebral spaces on the low resolution DPA images introduced errors in patient data. DRA may replace DPA as the dedicated projectional densitometric procedure of choice for technical reasons, but at present a conversion equation must be used to compare DRA data to DPA data. PMID- 2909086 TI - Image data compression in magnification hand radiographs. AB - A study was conducted on the use of an irreversible compression technique, Fourier quantization, to reduce the amount of digital data needed for an image. The effect of image compression was studied in radiographs obtained to diagnose subperiosteal bone resorption. Magnification radiographs of 44 hands were digitized to an array size of 4,096 X 4,096 X 12 bits. Selected subregions containing a single middle phalanx were compressed and reconstructed. A subset of the resultant 12-bit uncompressed and 8-, 7-, and 6-bit compressed images were read by four radiologists whose responses were analyzed with receiver operating characteristic (ROC) techniques. There were 81 images used in the ROC analysis, of which 48 were normal and 33 showed subperiosteal resorption. No statistically significant loss of diagnostic quality was detected for 8- or 7-bit compressed images, with average compression ratios of 16:1 and 28:1, respectively. Diagnostic quality was lost with 6-bit images, with an average compression ratio of 107:1. PMID- 2909087 TI - Bone and bone marrow changes in Gaucher disease: evaluation with quantitative CT. AB - The trabecular bone density and bone marrow fat content in eight patients with type 1 Gaucher disease were measured with the use of a modification of dual energy computed tomography (CT). The results were compared with those in published reports of single-energy quantitative CT measurements in healthy subjects and with dual-energy data obtained in studies of healthy premenopausal women and elderly osteopenic women. The trabecular bone mass was moderately decreased in patients with Gaucher disease. The bone marrow fat content was markedly diminished, presumably due to replacement of marrow fat by Gaucher cells. In healthy and osteopenic subjects single-energy quantitative CT values were lowered by the presence of marrow fat. Comparable single-energy measurements in patients with Gaucher disease reflect greater degrees of bone loss. Low levels of marrow fat may prove to be a valuable marker of the severity of marrow disease. PMID- 2909088 TI - Spinal cord compression in type I Gaucher disease. AB - Three patients with epidural compression of the spinal cord, a rare but serious complication of type I Gaucher disease, are described. In two cases the compression occurred at the lower thoracic region due to collapse of T-11 and T 12, respectively. In the third case, an epidural mass developed at the dorsal aspect of the cord at T-2, and T-2 and T-3 showed diffuse infiltration without collapse. In two cases the diagnosis was made with magnetic resonance (MR) imaging. In these cases MR imaging proved to be a safe, accurate method for demonstrating the nature and extent of disease within the spinal canal. PMID- 2909089 TI - Liver metastases: detection with MR imaging at 0.5 and 1.5 T. AB - Nineteen patients with known liver metastases were examined with two magnetic resonance (MR) pulse sequences at 0.5 T and three pulse sequences at 1.5 T. In addition, the patients were studied with computed tomography (CT) enhanced with ethiodized oil emulsion-13 (EOE-13). At 0.5 T a spin-echo (SE) 300/22 (repetition time/echo time, msec) sequence prospectively demonstrated 92.4% of the detectable liver metastases, while an SE 2,000/80 sequence showed 52.1% of the lesions. At 1.5 T, an SE 300/25 sequence depicted 68.3% and an SE 2,000/80 sequence 71.6%, while the more T1-weighted inversion recovery (IR) 2,000/600 (repetition time/inversion time, msec) sequence demonstrated 89.5% of the lesions. EOE-13 CT scans depicted 93.3%. These findings suggest that T1-weighted imaging is as successful at demonstrating liver metastases at 1.5 T with an IR 2,000/600 sequence as at 0.5 T with an SE 300/22 sequence. At both field strengths, MR imaging of the liver is comparable to state-of-the-art CT. PMID- 2909090 TI - Non-Hodgkin lymphoma: influence of lymphography, CT, and bone marrow biopsy on staging and management. AB - This prospective study assesses the contribution of lymphography (LAG), abdominal pelvic computed tomography (CT), and bone marrow biopsy to the staging and management of 168 consecutive cases of newly diagnosed non-Hodgkin lymphoma (NHL). LAG and/or CT influenced Ann Arbor clinical stage (CS) in 39 patients (23%) and Ann Arbor pathologic stage (PS) in 23 patients (14%) by detection of clinically inapparent retroperitoneal adenopathy and/or extranodal disease. LAG findings raised the CS in eight patients and the PS in six of the eight by showing adenopathy when the CT results were negative. By depicting extranodal disease, CT resulted in the CS being raised in an additional ten patients and the PS in six of the ten. Of the diagnostic tests assessed, bone marrow biopsy and/or cytology had the greatest influence on staging. Clinical staging that included LAG/CT resulted in the identification of only 30 patients with CS IV disease, whereas an additional 53 CS I through CS III patients had their disease stage raised to PS IV due to positive bone marrow biopsy/cytology results. However, 42 of the 53 patients already had advanced (CS III) disease. Initial case management was influenced by LAG, CT, or bone marrow biopsy/cytology results in 27 of 168 patients. LAG/CT results influenced management in 20 of 27 cases, while bone marrow biopsy/cytology results caused initial management changes in only seven of the 27 cases. PMID- 2909091 TI - Opacification of collecting ducts at urography. PMID- 2909092 TI - Evaluation of recurrent pyogenic cholangitis with CT: analysis of 50 patients. AB - The use of computed tomography (CT) was investigated in 50 patients with recurrent pyogenic cholangitis, 22 of whom had undergone prior choledochoenterostomy or sphincteroplasty. A spectrum of pathologic features was noted, including intrahepatic ductal dilatation (n = 50), common duct dilatation (n = 34), strictures (n = 11), intrahepatic calculi (n = 37), common duct calculi (n = 15), pneumobilia (n = 26), segmental atrophy (n = 18), and splenomegaly (n = 7). Unilobar disease existed in 14 patients. The left lateral segment was predominantly affected, with ductal dilatation (n = 23) and segmental atrophy (n = 13). During acute exacerbation, additional manifestations were observed: ductal wall enhancement (n = 4), segmental parenchymal enhancement (n = 9), hepatic abscess (n = 9), and biloma (n = 2). CT enables sensitive, complete evaluation of this disorder. It is valuable when results of ultrasonography are non-diagnostic and for planning hepatic resection, evaluating associated mass lesions, and guiding complex interventional procedures. PMID- 2909093 TI - Liver, spleen, and vessels: preliminary clinical results of CT with perfluorooctylbromide. AB - This phase 1-2 trial investigated the use of a 100% wt/vol emulsion of perfluorooctylbromide (PFOB) in computed tomography (CT) of 30 patients with metastatic cancer. Injection of 3 g/kg (maximum dose administered to these patients) provided an average liver enhancement of +31 HU on CT scans obtained after 48 hours. Maximum splenic opacification occurred immediately after injection; 1 g/kg, which allowed an immediate enhancement of +35 HU, appeared sufficient for the diagnosis of splenic conditions. Vascular opacification was insufficient for diagnostic purposes. In four patients with metastases, more lesions were seen with the use of PFOB with CT than with conventional CT. Adverse effects included five cases of low back pain that were reversible when the infusion rate was reduced. Fever and trembling were also noted 6 hours after injection in five patients. In all patients, symptoms regressed spontaneously within several hours. Clinically inapparent and dose-independent splenomegaly (volume increase of at least 20% on CT examinations) was noted in eight patients. PMID- 2909094 TI - Potential role of perfluorooctylbromide in the detection and characterization of liver lesions with CT. PMID- 2909095 TI - Gallstones: fragmentation with a tunable dye laser and dissolution with methyl tert-butyl ether in vitro. AB - The authors tested whether gallstone fragmentation with a tunable dye laser would speed dissolution with methyl tert-butyl ether (MTBE) and allow successful in vitro dissolution of calcified stones. Twelve sets of three stones matched for size and weight were obtained from 11 surgically resected human gallbladders and one common bile duct operation. Computed tomography was used to determine presence and distribution of calcium. One stone from each set was either chemically analyzed, mechanically fragmented with the laser, or left intact. Fragmented and intact stones were subjected to MTBE dissolution for 12 hours or until fragments were 2 mm or less in diameter. All five laser-treated, noncalcified gallstones dissolved completely, compared with four of five intact stones. All six laser-treated, calcified gallstones dissolved completely, compared with only one of six intact stones. The solitary calcified common bile duct stone, whether fragmented or intact, did not completely dissolve. Speed of dissolution was significantly faster for laser-treated stones (P = .04). The authors conclude that laser fragmentation of gallstones increases the speed of subsequent MTBE dissolution and allows successful dissolution of calcified gallstones. PMID- 2909096 TI - Left lobe of the liver: percutaneous biliary drainage. AB - Left-sided biliary drainage was performed in 89 of 678 (13%) patients undergoing percutaneous biliary drainage procedures during a 9-year period. The most common indication was Klatskin tumor, followed by sclerosing cholangitis, carcinoma of the gallbladder, postoperative benign stricture, and metastasis to the porta hepatis. Left-duct drainage was successful in 82 of the 89 patients (92%) in whom it was attempted. One patient sustained a major hemorrhage from a hepatic artery aneurysm, which was managed with transcatheter embolization. PMID- 2909097 TI - Perforated amebic liver abscesses: successful percutaneous treatment. AB - Perforation of hepatic amebic abscess is associated with high morbidity and may result in death. Traditional treatment has been emergency surgery. The authors report successful percutaneous drainage of perforated hepatic amebic abscesses in five severely ill patients. These perforations resulted in abscesses in the subhepatic space, pelvis, chest, right and left paracolic gutters, lesser sac, retroperitoneum, and flank. A total of ten intrahepatic abscesses also were drained in these patients. Catheter drainage lasted from 7 to 34 days and was combined with metronidazole therapy; the latter had been used for 1 week in two patients and in one patient for 2 days without success before drainage. Associated fistulas were demonstrated to the bile ducts, duodenum, and colon; all healed spontaneously. This experience suggests an expanded use of catheter drainage for perforation, a serious complication of amebic abscess. PMID- 2909098 TI - Idiopathic intracranial hypertension (pseudotumor cerebri): MR imaging. AB - Magnetic resonance (MR) imaging was performed on six patients with idiopathic intracranial hypertension (IIH). The patients were all women with a mean age of 27 years (range, 17-41 years). Six healthy women volunteers with a mean age of 33 years (range, 25-46 years) were studied for comparison. All six patients had elevated opening pressures at lumbar puncture. MR imaging demonstrated a partially empty sella in two patients, and one patient had signal aberration in the dural venous sinuses suggestive of slow flow. There were no white matter signal abnormalities, even in the periependymal space. Volumetric pixel analysis revealed significantly larger subarachnoid space volumes in patients than in control subjects, without a significant difference in ventricular volumes. No other intracranial abnormalities were found in any IIH patient or control subject. The results suggest that, in IIH, (a) although the subarachnoid spaces are enlarged, the wide range of normal values would limit the clinical use of these measurements and (b) the role of MR imaging, as with CT, is primarily in the exclusion of other diseases with clinical presentations similar to that of IIH. PMID- 2909099 TI - Idiopathic intracranial hypertension: pathogenesis and the role of MR imaging. PMID- 2909100 TI - Cocaine abuse: neurovascular complications. AB - In a review of the records of 3,712 drug abusers, 13 patients were identified with neurologic deficits attributable to the use of cocaine. Ischemic manifestations were the most frequent, occurring in seven (54%) patients, with a mean age of 34.2 years. Three (23%) patients had subarachnoid hemorrhage, and three (23%) had intracerebral hemorrhage. Three patients from other institutions were included in the analysis, for a total of 16 patients, (eight with cerebral ischemia, four with subarachnoid hemorrhage, and four with intracerebral hemorrhage). Of the six patients with head computed tomographic findings of cerebral infarction, five had subcortical infarcts. Two of the four patients who presented with a subarachnoid hemorrhage had a congenital intracranial aneurysm. One of the four patients with an intracerebral hemorrhage had an underlying arteriovenous malformation. The mechanism through which these complications occur is not completely understood. Factors that may play a role include the acute hypertensive response that occurs with cocaine use as well as disordered neurovascular control. PMID- 2909101 TI - Intradural spinal cord lesions: Gd-DTPA-enhanced MR imaging. AB - Twenty-five patients with suspected spinal cord neoplasms were studied with high field-strength magnetic resonance (MR) imaging (1.5 T) before and after administration of gadolinium diethylenetriamine-pentaacetic acid (DTPA) (gadopentetate dimeglumine). Five patients had enhancing, nonneoplastic lesions, including spinal dural arteriovenous fistulas (AVFs), cord infarction, and chronic arachnoiditis. Fifteen patients had proved spinal cord neoplasms, 13 intramedullary and two extramedullary. Four of the intramedullary tumors were detected only after Gd-DTPA administration; in five others, contrast material enhancement improved observer confidence. Gd-DTPA also demonstrated one dural AVF not detected on precontrast images. Regions of cord ischemia or infarction related to spinal dural AVF also enhanced in three patients. Advantages of Gd DTPA include the demonstration of small isointense intramedullary tumors and the ability to permit differentiation of tumor from adjacent cord syrinx and solid tumor from postoperative gliosis and arachnoid scarring. Gd-DTPA enhancement is a useful adjunct to high-resolution MR imaging of the spinal cord. PMID- 2909102 TI - Pituitary adenomas: possible role of bromocriptine in intratumoral hemorrhage. AB - Magnetic resonance (MR) images of 68 patients examined for adenomas of the pituitary gland were retrospectively reviewed for the presence of hyperintensity on T1-weighted images because of recent reports suggesting that bromocriptine treatment may affect T1 values. Twenty-seven patients were examined after either surgery or radiation therapy, 29 were receiving bromocriptine, and 22 had not received any treatment at the time of MR imaging. MR imaging criteria showed evidence of subacute or chronic intratumoral hemorrhage in 18 patients, five of whom had hemorrhage proved at surgery. Ten of the 18 patients were asymptomatic from the hemorrhage; eight had headaches, visual field cuts, or cranial nerve deficits. Although an increased frequency of intratumoral hemorrhage was noted in prolactinomas and macroadenomas and in patients undergoing bromocriptine therapy, the effect of bromocriptine on bleeding was the only significant correlation (P less than .01). PMID- 2909103 TI - Cardiac myxoma metastatic to the temporal bone. AB - Two metastases from an atrial myxoma occurred in the right common carotid artery distribution of a 34-year-old man. One metastasis caused the phenomenon of intracranial pseudoaneurysm in a distal branch of the middle cerebral artery. The other resulted in the unusual radiographic appearance of a tremendous, "bubbly" expansion of the temporal bone. PMID- 2909104 TI - Transalar sphenoidal encephaloceles: clinical and radiologic findings. AB - Two cases of occult basal encephalocele protruding through defects in the greater wing of the sphenoid bone are presented. The cases are unique in that they occurred in adults with non-localizing symptoms and were eloquently imaged by computed tomography (CT) and magnetic resonance (MR). While the theoretical existence of this type of encephalocele has been recognized, no documented cases of transalar sphenoidal encephalocele are known to have been reported in the radiology or surgery literature. PMID- 2909105 TI - Bilateral MR imaging with switched mutually coupled receiver coils. AB - The authors describe a system of bilateral mutually coupled receiver coils and its initial clinical use in magnetic resonance imaging of the knees and temporomandibular joints. Switched mutually coupled coils allow bilateral simultaneous imaging of paired structures without a penalty in signal-to-noise ratio because the coils can be alternated with each section acquisition. With this coil system, there is no restriction on placement or design of coils to prevent interaction. When combined with three-dimensional imaging techniques, switched coils allow simultaneous bilateral acquisition of multiple, contiguous sections through paired anatomic structures in a reasonable amount of imaging time. PMID- 2909106 TI - Whole-body echo-planar MR imaging at 0.5 T. AB - The ultra-high-speed echo-planar imaging technique produces instant snapshot magnetic resonance images in exposure times ranging from approximately 10 to 100 msec. A particular variant, the modulus blipped echo-planar single-pulse technique (MBEST), possesses two advantages: First, it makes the technique experimentally more robust; second, it introduces inherent T2 weighting in the images. The authors have used MBEST with an exposure time of 64 msec to explore the potential range of clinical applications in a series of normal volunteers. Applications include evaluation of the heart, renal function, and gastrointestinal tract. All images were obtained with proton resonances at 22 MHz. PMID- 2909107 TI - Comparison of cocurrent and countercurrent flow-related enhancement in MR imaging. AB - Patterns of flow-related signal loss and enhancement have been observed in fluid moving perpendicular to the imaging plane on multi-section-acquisition magnetic resonance images. These patterns depend on whether the flow is in the same direction (cocurrent) or opposite (countercurrent) to the direction of sequential section excitation. For a given velocity, flow-related enhancement penetrates deeper into the imaging volume with countercurrent flow than with cocurrent flow. The signal intensity of inner sections is generally greater with countercurrent flow than with cocurrent flow and depends on the velocity. These effects were investigated quantitatively with phantom studies and correlated with theoretical predictions. It was found that the limited penetration of flow-related enhancement with cocurrent flow is a consequence of recently saturated upstream protons flowing into the section to be excited. The flow-related enhancement penetrates farther with countercurrent flow, because inflowing spins have had a greater period of time to recover from the saturating effect of the radio frequency pulse. Because different laminae have different time intervals to recover magnetization, this also accounts for the observation of concentric rings representing laminar flow in the countercurrent direction. PMID- 2909108 TI - Nipple simulating a breast mass on a mammogram. AB - On a mediolateral mammogram obtained during routine screening, a mass was noted deep within the breast. However, no mass could be palpated, and additional views showed no mass. Observation of the patient during imaging demonstrated the nipple of the opposite breast was inadvertently projected onto the image. Radiologists should be aware of this cause of pseudotumor of the breast. PMID- 2909109 TI - Coaxial needles for repeated biopsy sampling. AB - A set of coaxial biopsy needles permits repeated tissue samples through an outer, larger needle that remains in place. The tract can be dilated from 23 to 16 gauge with the use of transfer rods, without loss of the initial position. The technique has been used successfully in six patients. PMID- 2909110 TI - Interactive real-time multiplanar CT imaging. AB - A new software program provides the real-time display of high-resolution computed tomographic reformation in the axial, coronal, sagittal, or oblique views. The advantages of this new technique over the standard multiplanar format include (a) larger image display format, (b) reconstruction of entire dataset for each of up to 192 sections, (c) real-time viewing, (d) interactive real-time oblique imaging, and (e) on-screen correlation of multiplanar and three-dimensional images. PMID- 2909111 TI - Medical malpractice claims in diagnostic radiology: update. PMID- 2909112 TI - Detection of asbestosis with high-resolution CT. PMID- 2909113 TI - Abnormal signal in deep white-matter infarction. PMID- 2909114 TI - MR imaging of transient osteoporosis. PMID- 2909115 TI - Reactions to ionic and nonionic contrast media. PMID- 2909116 TI - Transitional cell carcinoma of the upper urinary tract. PMID- 2909117 TI - Proposed list of abbreviations. PMID- 2909118 TI - Normal collecting ducts: visualization at urography. AB - In 21 of 636 patients with normal renal function and without obstruction of the upper urinary tract, urograms showed that contrast medium filled thin cylindrical structures in the renal pyramids with the same course as that of the collecting ducts. The prevalence of cylinders when the low-osmolality contrast medium iohexol was used was 21 of 158 studies (13.3%) and with the high-osmolality contrast medium amidotrizoate, two of 529 studies (0.4%). The cylinders were more distinct and more numerous with iohexol, while with amidotrizoate most cylinders appeared as striations. The cylinders appeared within 4 minutes from the start of contrast medium injection and remained distinct for 35-50 minutes. The diameter of the cylinders varied between 0.05 and 0.30 mm; their course was almost straight and closely followed the shape of the pyramid. The cylinders proved to consist of the highly opacified collecting duct lumina. Their configuration indicated that a single cylinder might be an individual collecting duct, but conclusive evidence was lacking. PMID- 2909119 TI - Anastomosed ureters: fluoroscopically guided transconduit retrograde catheterization. AB - Fluoroscopically guided, transconduit retrograde catheterization of ureters that have been diverted to a bowel conduit is often feasible in patients with patient ureteroenteral anastomoses who might otherwise require a percutaneous nephrostomy (PCN) for reasons other than high-grade anastomotic obstruction. This procedure was attempted on 14 occasions and successfully accomplished on 12. In 11 of these cases, retrograde catheterization obviated PCN to provide renal drainage for a partially obstructing ureteral stricture or obstructing renal calculi, to remove ureteral calculi, or to insert a new ureteral stent after an unsuccessful attempt to exchange an existing occluded retrograde ureteral stent. The procedure also obviated Whitaker testing. On one occasion the retrograde procedure greatly facilitated subsequent PCN in an obese patient with faintly opaque calyceal calculi. These procedures were accomplished with standard angiographic equipment and, in many instances, Teflon sheaths in the bowel conduit to stabilize catheters and guide wires. No complications were encountered. The two patients whose ureters could not be catheterized in retrograde fashion subsequently required PCN. PMID- 2909120 TI - Radiation-induced uterine changes: MR imaging. AB - To assess the capability of magnetic resonance (MR) imaging to demonstrate postirradiation changes in the uterus, MR studies of 23 patients who had undergone radiation therapy were retrospectively examined and compared with those of 30 patients who had not undergone radiation therapy. MR findings were correlated with posthysterectomy histologic findings. In premenopausal women, radiation therapy induced (a) a decrease in uterine size demonstrable as early as 3 months after therapy ended; (b) a decrease in signal intensity of the myometrium on T2-predominant MR images, reflecting a significant decrease in T2 relaxation time, demonstrable as early as 1 month after therapy; (c) a decrease in thickness and signal intensity of the endometrium demonstrable on T2 predominant images 6 months after therapy; and (d) loss of uterine zonal anatomy as early as 3 months after therapy. In postmenopausal women, irradiation did not significantly alter the MR imaging appearance of the uterus. These postirradiation MR changes in both the premenopausal and postmenopausal uteri appeared similar to the changes ordinarily seen on MR images of the nonirradiated postmenopausal uterus. PMID- 2909121 TI - Acute renal dysfunction in high-risk patients after angiography: comparison of ionic and nonionic contrast media. AB - A group of 145 high-risk patients who underwent angiography after administration of the nonionic contrast agent iohexol were monitored for the development of acute renal dysfunction. The results in this group were compared with those in 202 high-risk historical control subjects who had undergone angiography after administration of ionic contrast material. All patients in both groups received similar pre- and postangiographic treatment. A greater number of patients in the ionic group had preexisting renal disease, were of advanced age, and had received large volumes of contrast material. Acute renal dysfunction occurred in 20 of the 202 (10%) patients in the ionic group, compared with eight of the 145 (5.5%) patients in the nonionic group; this difference is not statistically significant. Five patients in the ionic group, but none of the patients in the nonionic group, ultimately required dialysis; this difference is not statistically significant. The findings suggest that a randomized trial in high-risk patients should be undertaken before a clinical advantage of the nonionic contrast agent iohexol with regard to renal function can be assumed. PMID- 2909122 TI - Mammography after prosthesis placement for augmentation or reconstructive mammoplasty. AB - Mammograms of 59 women who underwent placement of a prosthesis for augmentation or reconstructive mammoplasty were retrospectively reviewed. Free silicone was used in five women, retroglandular prostheses in 40, and subpectoral implants in 14. Abnormalities of prosthesis contour were seen only in eight women with retroglandular implants. In another four women, retroglandular prostheses became calcified. In women who received free-silicone injections, coarse calcifications developed in three, and gross nodularity with calcified silicone granulomas developed in one. Five palpable masses developed, three of which were malignant; four masses were in breasts augmented with a retroglandular prosthesis, and they could not be detected with mammography. The mass that developed in a woman with a subpectoral prosthesis could be seen at mammography. The only nonpalpable malignancy detected with mammography was in a breast with a retroglandular prosthesis and contained microcalcifications. The authors conclude that in women with retroglandular prostheses, masses may often be obscured on mammograms by compressed, dense glandular tissue. PMID- 2909123 TI - Residual breast carcinoma after biopsy: role of mammography in evaluation. AB - The records of 21 consecutive patients referred for breast-conservation treatment of early-stage mammary carcinoma contained insufficient histopathologic documentation of adequate resection margins after tumor excision at other hospitals. All patients underwent postbiopsy mammography before reexcision of the tumor bed. In 12 of the 21 cases, there was pathologic evidence of macroscopic or microscopic residual tumor. In seven of the 12 cases, there was no clinical or mammographic evidence to suggest residual carcinoma. The findings indicate that mammography is insufficient to evaluate the completeness of tumor excision in the absence of histopathologic documentation. PMID- 2909124 TI - Combination gel-inflatable mammary prosthesis: appearance at CT. AB - The combination gel-inflatable prosthesis is commonly used in breast reconstruction surgery following mastectomy for cancer. Since patients with this type of implant may be examined with computed tomography (CT) for possible pulmonary metastatic disease, recognition of the CT appearance is important in order to avoid the erroneous diagnosis of an infected prosthesis. A case is presented in which the CT appearance of a double-lumen prosthesis was misinterpreted as an infected prosthesis. PMID- 2909125 TI - HIV-associated lymphocytic interstitial pneumonia: radiologic manifestations and pathologic correlation. AB - The authors reviewed chest radiographs of 16 patients with biopsy-proved lymphocytic interstitial pneumonia (LIP) who also had acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC). Radiographs revealed fine reticular or reticulonodular infiltrates in the pulmonary interstitium in five patients, coarse reticulonodular infiltrates in two, and reticular or reticulonodular opacities with superimposed patchy alveolar infiltrates in nine. Pathologic examination of biopsy specimens revealed lymphocytes, plasma cells, and reticulum cells aggregated about the small arteries and compressing the distal airways. Throughout the course of AIDS or ARC, the radiographic findings of LIP remained stable in 12 of 16 patients. AIDS/ARC-related LIP appears to be a benign reaction of bronchial-associated lymphatic tissue to the human immunodeficiency virus (HIV). However, this indolent process cannot be correctly diagnosed based on radiographic findings alone; the use of lung biopsy is required to differentiate LIP from other infections. The authors suggest that patients with these radiographic findings, HIV seropositivity, but no other signs of opportunistic infection or neoplasia should be classified as having AIDS. PMID- 2909126 TI - Adrenal hemorrhage and renal vein thrombosis in the newborn: MR imaging. AB - Three newborn infants with flank masses underwent magnetic resonance (MR) imaging after ultrasound (US) indicated adrenal hemorrhage and/or renal vein and inferior vena cava thrombosis. MR imaging was valuable in defining the hemorrhagic nature of echogenic and hypoechoic suprarenal masses and in delineating thrombi within the renal veins and inferior vena cava. Two infants with renal parenchymal damage had abnormal radionuclide scans and abnormal corticomedullary distinction on MR images. The major role of MR imaging may be in the early course of these conditions, when added diagnostic specificity is likely to affect patient management. In most instances, size of hemorrhage and intravenous clots, as well as renal size, may be accurately followed with US, while radionuclide scanning remains necessary for evaluation of renal functional impairment. PMID- 2909127 TI - Computed arthrotomography as an adjunct to pediatric arthrography. AB - Computed arthrotomography was compared with conventional arthrography in ten cases and with both pluridirectional arthrotomography and conventional arthrography in five cases. Six elbows, five hips, three ankles, and one wrist were examined. Indications included pain, locking, congenital hip dislocation, posttraumatic joint deformity, and postinfectious joint deformity. Compared with conventional arthrography, computed arthrotomography provided additional information in ten of 15 (67%) cases and provided the same information in four cases. Arthrography and computed arthrotomography were complementary in one case. Compared with pluridirectional arthrotomography, computed arthrotomography provided additional information in two of five (40%) cases. In the remaining three cases, computed arthrotomography and pluridirectional arthrotomography provided equal information. In no case did pluridirectional arthrotomography provide additional information. Computed arthrotomography was useful in demonstrating loose bodies, differentiating air bubbles from loose bodies, and determining the intra- or extraarticular location of ossific densities. Computed arthrotomography appears to be a useful adjunct to arthrography in detecting loose bodies and in evaluating anatomically complex cases. PMID- 2909128 TI - Diverticular disease of the appendix. AB - A retrospective study of diverticular disease of the appendix was made in 3,343 consecutive instances of appendectomies. A 2 per cent incidence of diverticular disease was found. These instances were classified into four morphologic types: 1, acute diverticulitis; 2, acute appendicitis with acute diverticulitis; 3, acute appendicitis with diverticulum, and 4, appendix with diverticulum. Types 1, 2 and 3 were divided into subgroups with or without perforation. The elements of clinical behavior in each group were examined in detail. Diverticulitis of the appendix is presented as a clinically variant form of the inflamed appendix. Some followed the pattern of typical acute appendicitis. However, most were distinctive at a later age of onset, longer interval of disease, fewer or absent symptoms of the gastrointestinal tract, failure of typical abdominal pain progression, delay in surgical treatment and a remarkably high incidence of perforation. In a chi-square analysis of 56 patients with acute diverticulitis of the appendix compared with 2,503 patients with acute appendicitis, more than a fourfold incidence of perforation in acute diverticulitis was significant beyond the 0.001 level. These findings of variant behavior and high incidence of perforation are cautionary features of this frequently overlooked disease. PMID- 2909129 TI - Delayed debridement and external drainage of massive pancreatic or peripancreatic necrosis. AB - Thirty-six consecutive patients with massive tissue necrosis resulting from acute pancreatitis were initially managed nonoperatively. In each instance, a mass of necrotic tissue, bathed in fluid, became evident. Laparotomy was delayed unless a life-threatening complication developed. In no instance did the "cavitary necrosis" disappear prior to laparotomy. In five patients, laparotomy was avoided and a chronic pseudocyst evolved. Thirty-one patients required laparotomy, usually after a lapse of one to two months. The necrotic tissue was always retroperitoneal and was clearly demarcated from viable tissue. In most instances, the necrotic tissue was predominantly retroperitoneal adipose tissue. Under such conditions, the anatomic definition of the pancreas, per se, was not practical. The preoperative and operative diagnosis of secondary infection of the necrotic tissue was often difficult. The operation consisted of necrosectomy (debridement) and external drainage. The amount of necrotic tissue was often in excess of 1 kilogram. When necrosectomy was incomplete, secondary explorations and debridement were sometimes necessary. In retrospect, in only a few instances did necrosis and necrosectomy appear to have resulted in the loss of an appreciable amount of pancreatic tissue. One of the 36 patients died, giving a mortality rate that compares favorably with reports of earlier operative intervention. PMID- 2909130 TI - Long term results of treatment of Budd-Chiari syndrome by side to side portacaval shunt. AB - This is a report of a long term prospective study of 13 seriously ill patients with Budd-Chiari syndrome as a result of occlusion of the hepatic veins who were treated by side to side portacaval shunt from four to 78 weeks after the onset of symptoms and who were under observation for three to 16 years. The patient population was young, ranging in age from 19 to 45 years; seven were men and six were women. The presumed cause was the use of oral contraceptives in three, polycythemia rubra vera in two, Behcet disease in one patient and unknown in seven patients. All of the 13 patients had abdominal pain, marked ascites, hepatosplenomegaly, wasting and disturbed liver function. Diagnosis was based on the symptoms and signs: angiographic demonstration of hepatic vein occlusion and a patent inferior vena cava; pressure measurements that showed an inferior vena caval pressure that was normal or within the usual range for patients with massive ascites and an elevated wedged hepatic vein pressure that was much higher than the inferior vena caval pressure, and the results of biopsy of the liver showing centrilobular congestion and necrosis. Side to side portacaval shunt was very effective in decompressing the liver, reducing the mean corrected portal pressure from 240 millimeters of saline solution before to 7 millimeters of saline solution after the shunt. Operative survival rate was 92 per cent, and the long term survival rate for three to 16 years is 85 per cent. All of the survivors are free of ascites without requiring diuretic therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2909131 TI - Techniques and results in the management of anal and perianal Crohn's disease. AB - We reviewed our experience with 73 patients who had Crohn's disease and underwent local anorectal surgical procedures for perianal suppurative disease during a ten year period. All but one of these patients had intestinal granulomatous disease. The average length of follow-up study was 4.6 years. By using conservative, local anorectal surgical procedures and intensive medical treatment, we were able to establish adequate drainage of abscesses, reduce the inflammatory process and relieve symptoms. Extensive drainage procedures were avoided to preserve the anal sphincter. A sliding endorectal flap repair provided satisfactory results for rectovaginal fistulas and anterior anal fistulas. Proctectomy was eventually necessary in nine patients, the primary indication being severe perianal disease in five. By performing complete excision of the perineal disease at the time of proctectomy, we were able to achieve primary healing of the perineal wound in eight of these patients. Patients were classified according to five categories of results: healed after initial local treatment, eight patients; healed after more than one local treatment, 30 patients; incomplete healing with acceptable condition, 17 patients; healed after fecal diversion, nine patients, and required proctectomy, nine patients. The majority of patients with Crohn's disease and anal and perianal suppurative disease can be managed by meticulous drainage of sepsis and preservation of the anal sphincter. PMID- 2909132 TI - Left thoracotomy approach for resection of carcinoma of the esophagus. AB - One hundred and ten patients underwent gastroesophageal resections performed transdiaphragmatically by way of a left thoracotomy. Eighty-one patients had tumors distal to the inferior pulmonary vein and had en bloc dissections, while the remaining 29 had midthoracic tumors, which required a two-rib thoracotomy. There were 73 men and 37 women with a median age of 64 years (a range of 40 to 75 years). The postoperative mortality rate was 2.7 per cent, and morbidity, mainly caused by respiratory complications, occurred in 21 patients (19 per cent), with no patients requiring ventilatory support. There were no anastomotic leaks. Adequate analgesia was provided by the use of a subpleural catheter delivering a continuous infusion of bupivacaine. The left thoracotomy provides an effective method for undertaking esophageal resections with low mortality and morbidity rates. This approach should be more widely used in the surgical management of patients with intrathoracic esophageal tumors. PMID- 2909133 TI - Translumbar catheterization of the inferior vena cava for long term angioaccess. PMID- 2909134 TI - Clinical implications of anatomic variations of the splenic artery. AB - An aberrant course of the proximal splenic artery was observed in nine of 26 adult cadavers dissected for mapping of the lesser omentum. Such an aberrant course makes the artery vulnerable to iatrogenic injury. In view of this relatively high prevalence of splenic artery aberration, it is suggested that surgeons operating in the area of the lesser omentum should keep in mind the possibility of its occurrence and the dangers that it may present. PMID- 2909135 TI - Use of EEA stapler in reconstruction after gastric resection. AB - Herein is described our technique and experience with the EEA stapler in performing the Billroth I and II gastrectomies and Roux-en-Y reconstructive procedures. We did not perform a gastrotomy or an enterotomy to achieve the desired end to end or end to side anastomosis, thus avoiding another site to be closed later. In its single application, the EEA stapler gives a double layer of staggered staples, which results in a uniform and satisfactory healing. The removal of a ring of tissue with a central core, with examination for its completeness, assures a satisfactory anastomosis. The completed anastomosis can be examined under vision for any bleeding. As a final step, a TA 90 stapler is used at the desired line of transection of the stomach. This method of intestinal anastomosis shortens the operative time and creates a better anastomosis. We have performed these procedures upon 33 patients with good results. PMID- 2909136 TI - A simple method for preventing blood-borne contamination to operating room personnel during vascular reconstructive operations. AB - Although the risk of infection with hepatitis or HIV remains low, and the effectiveness of steps to reduce even this small risk is difficult to assess, the sequelae of the infection with either virus are often devastating. We described herein the use of a sterile Petri dish to inspect vascular anastomoses during arterial reconstructive operations. This simple, inexpensive precaution has been in use at the University of Cincinnati for two years and has proved so effective in preventing the contamination of operating room personnel with blood from a patient that it has recently become a routine part of all vascular reconstructive operations. PMID- 2909137 TI - Teaching laser bronchoscopy with laboratory models. PMID- 2909138 TI - Effect of felodipine on hyperventilation-induced ischemic attacks in variant angina pectoris. PMID- 2909139 TI - Right ventricular ischemia and proximal right coronary artery narrowing indicated by exercise ST-segment elevation in lead V1. PMID- 2909140 TI - Clinical application of deoxyribonucleic acid markers in a Utah family with hypercholesterolemia. PMID- 2909141 TI - Therapeutic efficacy and safety of oral propafenone for atrial fibrillation. PMID- 2909142 TI - Automatic implantable cardioverter defibrillator implantation for malignant ventricular arrhythmias associated with congenital heart disease. PMID- 2909143 TI - Pacemaker-induced ventricular tachycardia in normally functioning ventricular demand pacemakers. PMID- 2909144 TI - Differential effect of nicotine on plasma norepinephrine levels in normal humans and in patients with congestive heart failure. PMID- 2909145 TI - One-year follow-up after percutaneous double balloon mitral valvotomy. PMID- 2909146 TI - Mode of failure of the Hancock pericardial valve xenograft. PMID- 2909147 TI - Comparison of results of percutaneous balloon mitral valvotomy using single and double balloon techniques. PMID- 2909148 TI - Congenitally quadricuspid aortic valve: analysis of six necropsy patients. PMID- 2909149 TI - Predictors of sudden death in idiopathic dilated cardiomyopathy. PMID- 2909150 TI - Exercise capacity after acute aminophylline administration in angina pectoris. AB - Exercise-induced ischemia is generally attributed to an increase in myocardial demand in the presence of coronary stenosis limiting flow supply. An additional mechanism--the occurrence of coronary steal due to excessive endogenous adenosine release--has also been hypothesized. The effect of adenosine receptor blocking by aminophylline in effort ischemia was tested in 8 patients with stable effort induced angina pectoris, reproducible positive exercise stress tests and angiographically assessed coronary artery disease. Following double-blind, randomized intravenous infusion of aminophylline (3 mg/kg over 3 minutes) or placebo (20 ml of saline over 3 minutes), the patients underwent upright bicycle exercise stress tests on 2 consecutive days. After aminophylline, there was an increase in work tolerance (aminophylline 7.5 +/- 1.8 minutes of exercise vs placebo 5.4 +/- 1.5 minutes; p less than 0.05). There was a parallel increase in the ischemic threshold, evaluated with the rate-pressure product (mm Hg X beats/min X 100(-2)) at 0.1 mV of ST-segment depression (221 +/- 35 vs 184 +/- 20; p less than 0.01). Thus, at a dosage that should effectively inhibit adenosine receptors, aminophylline infusion exerts a beneficial effect on exercise-induced ischemia, possibly through the prevention of myocardial flow maldistribution elicited by excessive adenosine release during effort. PMID- 2909151 TI - Fistulous communications between a solitary coronary artery and the pulmonary arteries as the primary source of pulmonary blood supply in tetralogy of Fallot with pulmonary valve atresia. PMID- 2909152 TI - Echocardiographic evidence of pericardial effusion in severe chronic pulmonary hypertension. PMID- 2909153 TI - Doppler echocardiographic demonstration of pulmonary venous flow velocity in three patients with constrictive pericarditis before and after pericardiectomy. PMID- 2909154 TI - A multipurpose steerable catheter for left-sided cardiac catheterization. PMID- 2909155 TI - Dilated cardiomyopathy in multicore myopathy. PMID- 2909156 TI - Early detection and management of left ventricular free wall rupture during acute myocardial infarction. PMID- 2909157 TI - Hyperventilation and ergonovine tests in Prinzmetal's variant angina pectoris in men. AB - Hyperventilation and ergonovine tests were carried out in a group of 30 patients with variant angina to assess the sensitivity of the 2 tests and to correlate the response with spontaneous disease activity. Hyperventilation produced a positive response in 83% (25 of 30) and ergonovine in 93% (28 of 30) of the patients. After hyperventilation 22 of 25 showed ST-segment elevation, 2 ST depression and 1 T-wave pseudonormalization; after ergonovine ST-segment elevation developed in 23 patients, ST depression in 4 and T-wave pseudonormalization in 1. In all cases the electrocardiographic changes occurred in the same leads as during the spontaneous attacks. The incidence of chest pain and ventricular arrhythmias was similar during both tests; spontaneous remission of ischemia, however, was more frequent (48 vs 14%) after hyperventilation than after ergonovine. Acute ischemia developed at a mean of 218 +/- 112 seconds after the end of hyperventilation in 19 of 25 positive tests; at that time double product was not significantly different from basal values. The sensitivity of hyperventilation was similar (95 vs 100%) to ergonovine in the patients with greater than or equal to 1 daily attack, while in those with less than 1 daily attack the sensitivity of hyperventilation decreased to 55% compared to 77% with ergonovine. Thus, in variant angina the sensitivity of both tests correlates with disease activity. Hyperventilation is a safe provocative test with a sensitivity similar to ergonovine in patients with active disease; however, in patients with sporadic attacks hyperventilation has a lower sensitivity than ergonovine and therefore a limited diagnostic value. PMID- 2909158 TI - Invalidation of the resting electrocardiogram obtained via exercise electrode sites as a standard 12-lead recording. AB - The difficulty in interpreting the standard 12-lead electrocardiogram (ECG) due to the interference from muscle potentials produced by arm and leg motion makes it unsuitable during the exercise treadmill test. Likewise, the exercise lead placement ECG cannot substitute for the standard ECG due to significant errors in the former's diagnostic interpretation. This study compares the ECGs recorded via standard and exercise sites regarding frontal and horizontal plane axes, diagnosis and location of myocardial infarction and estimation of infarct size using the complete 54-criteria and 32-point Selvester QRS scoring system. The altered limb lead locations on the exercise ECG caused the QRS vectors to artifactually appear to be directed more inferiorly, posteriorly and rightward, producing a marked rightward mean frontal plane axis shift of +48 degrees (p less than 0.00001). No false positive or false negative anterior infarct was seen on the exercise lead placement ECG, whereas inferior and posterior infarcts were lost in 69% and 31% of patients, respectively. A false lateral infarct was seen in 19% of patients. Estimation of infarct size differed between the 2 ECG sets, with 11 patients increasing their infarct size by 3 to 9% and 14 others decreasing it by 3 to 15% on the exercise lead placement ECG. This study demonstrates that use of body torso positions for limb leads results in substantial QRS waveform variations that disqualify the exercise lead placement ECG as a "standard" recording. Such ECGs should therefore be labeled as "torso positioned" or "nonstandard" to prevent misuse for clinical and investigative purposes. PMID- 2909159 TI - Optimal sampling interval to estimate heart rate at rest and during exercise in atrial fibrillation. AB - To investigate the ideal sampling interval for the estimation of heart rate (HR) at rest and during exercise in atrial fibrillation (AF), maximal exercise testing with continuous electrocardiographic acquisition was performed in 10 patients with chronic AF (mean age 66 +/- 4 years) and 10 subjects in normal sinus rhythm (mean age 31 +/- 6 years). Measurements of HR were obtained at 9 different sampling intervals (1, 2, 3, 6, 10, 15, 20, 30 and 60 seconds) at rest and 7 different sampling intervals (1, 2, 3, 6, 10, 15 and 20 seconds) during the last 30 seconds of each minute during exercise. The HR obtained from each interval was compared with true HR (determined by a 4-minute sample at rest and by the last 30 seconds of each minute during exercise). Among patients with AF, large differences were observed between the HR obtained and true HR, both at rest and during exercise, using small sampling intervals. The mean of these differences ranged between 16 +/- 11 beats/min (range 14 to 22) using 1-second sampling intervals and 2.2 +/- 2.0 beats/min (range 1.6 to 4.4) using 20-second sampling intervals during progressive exercise. Variability of the HR obtained from a given random sample was also high when short sampling intervals were used among patients with AF. These observations were contrasted by subjects in normal sinus rhythm, among whom neither variability nor measurement error were influenced remarkably by changing the sampling interval or increasing HR. PMID- 2909160 TI - Isoproterenol induction of vasodepressor-type reaction in vasodepressor-prone persons. AB - The ability of isoproterenol to induce symptoms and laboratory findings of a vasodepressor reaction was tested in 48 patients, ages 17 to 74, divided into 4 groups according to the reason for their referral. Group 1 comprised 12 patients with vasodepressor syncope, group 2 had 8 patients with syncope of unknown origin, group 3 included 11 patients with syncope due to seizures in 2 and ventricular tachycardia in 9, group 4 had 17 patients with various arrhythmias not associated with syncope. Isoproterenol boluses were administered starting at 2 micrograms and increased in 2-micrograms steps to a maximum of 8 micrograms at 0 degree and +60 degrees. The responses at 0 degrees were all normal. At +60 degrees a vasodepressor reaction consisting of syncope or near syncope, hypotension and bradycardia was produced by isoproterenol (mean dose 6.0 +/- 0.26 micrograms) in 8 patients from group 1 (66.6%), 4 from group 2 (50%), 0 from group 3 and 4 from group 4 (23.5%). Three of the 4 patients in group 4 had a remote history of classic vasodepressor syncope. The overall sensitivity and specificity of the test were 73 and 85%, respectively, while the predictive accuracy of a test with positive or negative outcome were 69 and 89%, respectively. Muscarinic receptor blockade with atropine in 4 patients prevented isoproterenol-induced bradycardia but not hypotension or symptoms of fainting. Beta-adrenergic receptor blockade with propranolol inhibited all aspects of the isoproterenol-induced faint. Thus, the administration of isoproterenol during a passive upright tilt may identify persons who suffer from or are prone to a vasodepressor reaction. PMID- 2909161 TI - Cardiac electrophysiologic and hemodynamic correlates of neurally mediated syncope. AB - This study assessed the temporal relation of RR interval, AH interval and systemic blood pressure changes during induced symptomatic bradycardia hypotension episodes in 14 patients with recurrent syncope suspected of being neurally mediated. Upright tilt with isoproterenol reproduced symptoms in 9 of 14 patients (positive response) and was negative in 5 of 14 (negative response). Isoproterenol alone shortened supine RR intervals in all patients. With tilt, however, isoproterenol prolonged RR intervals in those with positive results (supine 519 +/- 124 ms vs tilt 845 +/- 212 ms, p less than 0.005) while further shortening RR intervals among negative responders (supine 436 +/- 90 ms vs tilt 377 +/- 82 ms, p less than 0.05). Similarly, tilt with isoproterenol prolonged AH intervals in patients with positive responses despite RR prolongation, while shortening AH in negative responders. Additionally, with combined tilt and isoproterenol, systemic arterial pressure decreased significantly in patients with positive responses (systolic 99 +/- 13 vs 57 +/- 13 mm Hg, p less than 0.001, diastolic 62 +/- 17 vs 28 +/- 9 mm Hg, p less than 0.001) but not in patients with negative responses. Further, onset of hypotension (42 +/- 14 seconds after tilt) preceded onset of RR interval prolongation (52 +/- 23 seconds after tilt). Syncope (142 +/- 72 seconds after tilt) coincided closely with nadir of systemic pressure (136 +/- 74 seconds) and both tended to precede maximum RR prolongation (152 +/- 87 seconds). Thus, the bradycardia and hypotension associated with neurally mediated syncope exhibit characteristic but distinctly different time courses, with arterial pressure changes developing earlier and coinciding more closely with symptom development. PMID- 2909162 TI - Treatment of symptomatic peripheral atherosclerotic disease with a rotational atherectomy device. AB - Narrowings 70 to 90% in diameter in 3 iliac, 4 superficial femoral and 2 popliteal arteries were crossed and atherectomized successfully in 6 patients using the Squibb Rotablator under angiographic guidance during surgical bypass procedures on these arteries. The Rotablator consists of a 1.25 to 4.5 mm diameter oblong burr with tiny diamond blades mounted on a flexible shaft, which tracks over a spring-tip guidewire and rotates at speeds greater than 120,000 rpm. All stenoses were reduced to less than or equal to 50% of the normal luminal diameter. No significant complications occurred. Of the 6 patients having the atherectomy procedure, 5 were reevaluated by duplex Doppler measurements 1.5 to 5.5 (mean 3.5) months after atherectomy and found to be patient with only mild residual flow disturbance. Repeat follow-up by angiography after a mean of 5.2 months, however, showed only 3 (37%) of the atherectomized segments in 3 patients to still be patent. All were symptomatically improved. Of the effluent particles analyzed, 90% were less than 8 microns in size, while only 5% reached 250 microns. With improvements in technique, the largest particles were 150 to 180 microns, constituting only 1.4% of effluent debris. Samples of the effluent from 2 patients were injected in vivo into the left coronary system of 2 pigs. There were no acute hemodynamic or electrocardiographic complications or pathologic evidence of muscle necrosis or vascular thrombosis 18 to 48 hours later. These preliminary results with respect to feasibility and safety of the Rotablator are promising. PMID- 2909163 TI - Left ventricular exercise echocardiographic abnormalities in apparently healthy men with exertional hypotension. AB - Of a total of 1,435 healthy untrained asymptomatic individuals referred for a routine periodic checkup, 23 subjects with exertional hypotension on upright bicycle stress testing were identified. All were male. This study assesses by means of echocardiography the responses to exercise of left ventricular (LV) volumes, ejection fraction and segmental LV contractility in these subjects. Exertional hypotension was defined as a decrease in systolic blood pressure to below the resting value at the end of stress test. Supine systolic blood pressure after exercise was significantly greater in the control group than in the study group (179 vs 121 mm Hg, respectively; p less than 0.001); there was no significant intra- or intergroup difference in the resting values. In the study group end-systolic volume was 37 ml at rest and 35 ml after exercise; ejection fraction varied from 65% at rest to 63% after exercise. The sex- and age-matched control group with a normal systolic blood pressure response to exercise showed a shift from 35 to 23 ml and 65 to 77%, respectively (p less than 0.01 and 0.001). Ejection fraction correlated well with radionuclide angiography values. Exertional hypotension was noted after both upright and supine exercise. The pattern of regional wall motion remained unchanged or was hypokinetic in 87% of the subjects; only 13% presented the normally expected hyperkinesia after exercise. This study demonstrates that exertional hypotension is accompanied by an abnormal LV performance. PMID- 2909164 TI - Limited assurances. PMID- 2909166 TI - Human genetics education in medical schools--forward ho! PMID- 2909165 TI - A dicentric recombinant 9 derived from a paracentric inversion: phenotype, cytogenetics, and molecular analysis of centromeres. AB - A 4-year-old girl with multiple malformations and severe developmental delay has been shown to have a karyotype of 46,XX-9,+rec(9),dup p,inv(9) (q22.1q34.3)mat, with duplication 9pter-q22.1 and deficiency 9q34.3-qter. This case confirms that a stable recombinant chromosome can result from a paracentric inversion. The recombinant was derived by two crossovers, one within the inversion loop and a second outside the inversion loop, between 9q21 and the beginning of the meiotic inversion at 9q22.1. In 87 cells the rec(9) had one Cd-positive primary constriction. In 13 cells the rec(9) had two primary constrictions; in 12 of these cells there was one Cd-positive centromere, and in one of these cells both primary constrictions were Cd-positive. Nuclear projections were observed in 10% of fibroblast interphase cells harvested in situ, suggesting that there was some spindle-fiber activity of the "latent" centromere. In situ hybridization with a centromere-specific probe (p82H) and a satellite III probe (L6) revealed no differences between the two C-band regions of the rec(9) and the normal 9 or inverted 9 chromosomes. PMID- 2909167 TI - Report of the Task Force on Teaching Human Genetics in North American Medical Schools. PMID- 2909168 TI - Toward an ideal human genetics curriculum in medical schools. PMID- 2909169 TI - On the genetics of prelingual deafness. AB - In view of the many discordant findings in previous studies regarding the genetics of prelingual deafness, family data (133 nuclear families and 25 pedigrees) were gathered from India. Analysis of these data has revealed that the defect is primarily genetic, which is in agreement with earlier findings. Segregation analysis was performed to compare various autosomal diallelic one locus and multilocus models. Our analysis revealed that the most parsimonious model for prelingual deafness is that it is controlled by recessive genes at a pair of unlinked diallelic autosomal loci. Individuals are affected if and only if they are recessive homozygous at both loci. The likelihood of the present data under this two-locus multiple recessive homozygosis model is at least 10(8) times higher than that of the one-locus models that were examined in previous studies. This model is also the best-fitting model among other plausible two-locus models. PMID- 2909170 TI - In touch: telephone message system for teenagers. PMID- 2909171 TI - Gonorrhea rates: what denominator is most appropriate? PMID- 2909172 TI - Comments on meta-analysis. PMID- 2909173 TI - Worksite health promotion. PMID- 2909174 TI - Potential for exposure to tick bites in recreational parks in a Lyme disease endemic area. AB - Eight recreational parks located in a Lyme disease endemic area of southern New York State were surveyed for the presence of ticks during the summer of 1985 by drag sampling. Ixodes dammini, the primary vector of Lyme disease in the northeast, was found in all but one park and accounted for 580 (91.8 per cent) of the 632 ticks collected. Of these, 18 per cent were larvae, 80 per cent were nymphs, and 2 per cent were adults. An I. dammini encounter distance, defined as the mean number of meters traveled before encountering a nymphal or adult I. dammini on a drag cloth, ranged from 36 m in high-risk parks, to infinity (no tick encounters). Generally, areas of high use presented higher encounter distances (lower risk) than those of the entire park. Two of the three parks with the highest annual attendance also had the highest I. dammini population indices as projected from our sampling regimen. These results indicate that recreational parks in Lyme disease endemic areas represent a substantial human risk for tick bites and Lyme disease. PMID- 2909175 TI - Frequency of worksite health promotion activities. AB - The first National Survey of Worksite Health Promotion Activities surveyed a random sample of all private sector worksites with 50 or more employees, stratified by number of employers, geographic location, and type of industry. The 1,358 completed interviews constituted a response rate of 83.1 per cent. Of responding worksites 65.5 per cent had one or more areas of health promotion activity with slightly more than 50 per cent of activities initiated within the previous five years. Overall prevalence by type of activity included health risk assessment (29.5 per cent), smoking cessation (35.6 per cent), blood pressure control and treatment (16.5 per cent), exercise/fitness (22.1 per cent), weight control (14.7 per cent), nutrition education (16.8 per cent), stress management (26.6 per cent), back problem prevention and care (28.5 per cent), and off-the job accident prevention (19.8 per cent). Mean number of activities across all worksites was 2.1 and for worksites with activities, 3.2. Activity frequency increased with worksite size, was highest in the western region (2.34) and lowest in the northeast (1.96), and varied considerably by industry type. The majority of worksites paid the entire cost of these activities. PMID- 2909176 TI - National trends in the use of preventive health care by women. AB - This study investigates national changes between 1973-74 and 1985 in women's use of three preventive health services based on data from the National Health Interview Survey. Smoothed proportions of women with recent preventive care were estimated using weighted least squares for subgroups categorized by age (20-39, 40-59, 60-79), race (White, Black), income (poor, nonpoor), and year of interview. Older women and Black women experienced the largest increases in recent use of clinical breast examinations and Pap tests. Between 1973 and 1985 changes in recent breast examination ranged from zero for White women ages 20-39 years to a 23 percentage point increase (95% CI = 17,30) for Black women ages 60 79 years. A similar pattern was found for Pap testing. Changes between 1974 and 1985 in recent blood pressure testing ranged from zero for women ages 20-39 years to an 8 percentage point increase (95% CI = 6, 10) for women ages 60-79 years. Despite the increases among older women, in 1985 recent use of breast exams and Pap tests remained lower among older women. Further, the poor remained less likely than the nonpoor to have recent preventive care (except blood pressure testing among older women). Most women without recent cancer screening tests had a recent physician contact, highlighting the need for greater emphasis on cancer prevention by health care providers. PMID- 2909177 TI - Resistance to sexual assault: who resists and what happens? AB - To determine who resists sexual assault and what happens, data were examined from a probability sample of 3,132 adult community residents of Los Angeles, California. Seventy-five per cent of the respondents reporting an assault (n = 365) indicated that they had attempted to resist their most recent assault; talking was the most frequently used resistance strategy. The strongest predictor to emerge in the multivariate analyses of resistance was timing of assault: respondents assaulted only in childhood were less likely to resist than either respondents assaulted only in adulthood, or respondents assaulted in both phases. Univariate analyses indicated that resistance reduced the probability of sexual contact, however multivariate analyses suggested that assailant use of force was the most important determinant of assault outcome. PMID- 2909178 TI - Breastfeeding trends in the Philippines, 1973 and 1983. AB - This paper examines comparable national surveys of breastfeeding from the Philippines carried out in 1973 and 1983. The probability of breastfeeding at selected infant ages is estimated, using the weighted life table. The conclusions are that a 5 per cent decline in the proportion of infants ever breast-fed occurred during the referenced period, and that median length of breastfeeding remained essentially the same. PMID- 2909179 TI - A recent increase of breastfeeding duration in Jakarta, Indonesia. AB - Comparison of breastfeeding practices from two similar surveys conducted in Jakarta, Indonesia shows an increase in breastfeeding duration from 14.4 months in 1976 to 19.8 months in 1983. This increase was predominantly among noneducated women (20.3 months among noneducated women versus 0.9 months among women with greater than elementary education). Among working women breastfeeding duration declined slightly (1.1 months). Unlike industrialized countries where increases in breastfeeding have occurred initially among the higher socioeconomic groups, recent increases in Jakarta have occurred initially among the lower socioeconomic groups. If breastfeeding practices among working or better educated women who delivered mostly in hospitals or clinics are to be improved, the breastfeeding promotion programs should be targeted to these groups. PMID- 2909180 TI - Cryptosporidiosis and surface water. AB - In the period July through October, 1986, 78 laboratory-confirmed cases of cryptosporidiosis were identified in New Mexico. To determine possible risk factors for development of this disease, we conducted a case-control study; 24 case-patients and 46 neighborhood controls were interviewed. Seventeen (71 per cent) of the 24 case-patients were females, seven (29%) were males; their ages ranged from 4 months to 44 years, median 3 years. There was a strong association between drinking surface water and illness: five of the 24 case-patients, but none of the 46 controls drank untreated surface water. Among children, illness was also associated with attending a day care center where other children were ill (odds ratio = 13.1). PMID- 2909181 TI - A prospective follow-up study of cancer mortality in relation to serum DDT. AB - Serum DDT and DDE levels were measured in 919 subjects in 1974 and 1975. Two hundred and nine of the subjects died, including 54 from cancer, during a 10-year prospective follow-up period. There was no relation between either overall mortality or cancer mortality and increasing serum DDT levels. There was weak evidence of a positive relation between respiratory cancer mortality and serum DDT. The literature on DDT and human cancer is reviewed, and it is concluded that the evidence does not support the opinion that DDT is a human carcinogen. PMID- 2909182 TI - Barriers to implementation of a prenatal care program for low income women. AB - By the middle of the second year of the Michigan Prenatal/Postpartum Care (PPC) program to provide pregnancy-related services to low income women who were ineligible for Medicaid or other insurance, only 25 per cent of the participating health departments were enrolling greater than 90 per cent of contracted potential clients. Using a survey of program directors and relevant state documents, we identified several barriers to successful implementation: institutional (program complexity, high levels of administrative concerns along with low levels of communication between local health departments and providers); economic (inadequate resources for provider reimbursement, outreach, transportation, high-risk pregnancies, or administrative overhead); psychological (servicing populations with multiple and hard to care for problems, potential discomfort of low income women with traditional providers); and informational (insufficient information about the program infiltrating the target community). PMID- 2909183 TI - A study of battered women presenting in an emergency department. AB - Medical records of female trauma patients were retrospectively reviewed prior to introducing a protocol for enhancing identification of battered women; 5.6 per cent of 359 female trauma patients were identified as having injuries caused by battering; 30 per cent of 412 patients following use of the protocol were so identified. Standardized protocols for identifying battered women among female trauma patients should be instituted in emergency departments. PMID- 2909184 TI - Tea and premenstrual syndrome in the People's Republic of China. AB - We evaluated the hypothesis that tea consumption causes premenstrual syndrome by studying 188 nursing students and tea factory workers in the People's Republic of China via questionnaires distributed in classes (nursing students) or during routine physical examinations (tea factory workers). Analysis of the data revealed that tea consumption is strongly related to the prevalence of premenstrual syndrome and that the effects are dose-dependent. PMID- 2909185 TI - Differences in the timeliness of diagnosis, breast and cervical cancer, San Francisco 1974-85. AB - Cancer registry data for San Francisco (1974-85) were used to identify women at greater risk of late diagnoses for breast and cervical cancers by age and ethnicity. For breast cancer, Black women were at greater risk for late diagnoses. For cervical cancer, women of all ethnic groups ages 50-69 years and Japanese and Filipino women were at greater risk for late diagnoses. PMID- 2909186 TI - Breast cancer incidence in young women by estrogen receptor status and race. AB - A population-based study was utilized to calculate breast cancer incidence rates in White and Black women, ages 30 to 54, according to tumor estrogen receptor status. Both racial groups had higher incidence curves for estrogen receptor negative breast cancer between ages 30 and 49. There was an excess of receptor negative cancer in young Black women, an observation that may help explain the racial disparity in breast cancer survival. PMID- 2909187 TI - Bowel function and breast cancer in US women. AB - We studied bowel function in relation to 123 breast cancer cases among 7,702 women from the US NHANES I Epidemiologic Follow-up Study. Results suggest a slight increased risk of breast cancer for both decreased frequency of bowel movements (relative risk = 1.5, 95% confidence interval = 0.8, 2.7) and firm stool consistency (RR = 1.8, 95% CI = 1.0, 3.2.) These observations are consistent with an hypothesized association between constipation and increased risk of breast cancer. PMID- 2909188 TI - X-ray examinations during pregnancy: National Natality Surveys, 1963 and 1980. AB - Based on 1963 and 1980 National Natality Surveys, the rate of medical x-ray examinations during pregnancy per 100 mothers fell 34.2 percent. A decrease in chest x-ray examinations accounted for almost all of the decline in total x-ray examinations. The reductions were greater for older mothers and those who were not White. While the number of births fell from 4,071,000 in 1963 to 3,612,000 in 1980, the number of pelvimetry examinations actually increased by 45,000. PMID- 2909189 TI - Records, recall loss, and recall bias in pregnancy: a comparison of interview and medical records data of pregnant and postnatal women. AB - To determine the agreement between interview-based and medical records data concerning illnesses and medications early in pregnancy, we compared the interviews of 202 women with the ongoing records collected during their pregnancies. Substantial underrecording of most transient illnesses was found. Fewer short-term illnesses were reported by postpartum women than sill-pregnant women, suggesting the potential for recall bias or loss. PMID- 2909190 TI - HIV seroprevalence in intravenous drug users: Los Angeles, California, 1986. AB - To estimate the seroprevalence and investigate risk behaviors for HIV (human immunodeficiency virus) infection in intravenous drug users in Los Angeles County, a stratified, random sample of 790 clients, enrolled in either methadone maintenance or detoxification programs, were studied. Thirteen study participants (1.8 per cent) were seropositive; of these, five were homosexual/bisexual males and three were female prostitutes. Ninety-five per cent of all participants reported sharing needles. Risk reduction education efforts must be expanded before the HIV antibody prevalence rate increases. PMID- 2909191 TI - An outbreak of syphilis on an Indian reservation: descriptive epidemiology and disease-control measures. AB - From January 1983 through January 1985, 88 cases of early adult syphilis and five cases of congenital syphilis were identified among residents of a southwestern Indian reservation. The male-to-female ratio of primary and secondary syphilis cases was 1.7: 1; over 90 per cent of women were of childbearing age. Using community health workers to determine the social circles of infected persons was effective in identifying persons at risk; treatment of partners of infected persons prior to development of seroreactivity contributed to the successful control of this outbreak. PMID- 2909192 TI - The continuing saga of Lyme disease. PMID- 2909193 TI - Malignant lymphoma. A study of 75 cases presenting in soft tissue. AB - We report 75 cases of malignant lymphoma presenting in soft tissue taken from the files of the Armed Forces Institute of Pathology. All histologic subtypes with the exception of lymphoblastic lymphoma were represented. Our findings indicate that virtually any soft tissue site may be involved; there is no sex predilection; and size is not helpful in predicting survival. Among the 55 patients for which race was known, there were no black patients. Thirty-three patients with extensive evaluations at the time of diagnosis had no evidence of disseminated disease, but eight of these exhibited widespread disease within 3 months of diagnosis, and seven of the eight died of disease (median survival, 4 months). The remaining 25 patients had much better outcomes; 18 of 19 with intermediate and high-grade lymphomas were alive and well at a median of 74 months after diagnosis. Some tumors exhibited a propensity for involvement of remote soft tissue sites. PMID- 2909194 TI - Relationship between length of longitudinal extension and maximal depth of transmural invasion in roentgenographically occult squamous cell carcinoma of the bronchus (nonpolypoid type). AB - This study was designed to verify our hypothesis that there are two different growth types in roentgenographically occult squamous cell carcinoma of the bronchus. Serial blocks prepared from the entire bronchial tree of 83 resected specimens of occult carcinoma were used for the evaluation of the relationship between the length of longitudinal extension and the maximal depth of transmural invasion. We prepared a length-depth diagram of 92 lesions, including multifocal carcinomas, which confirmed that there are at least two types: Most of these lesions are of the creeping type, which shows a marked superficial growth; the minority are of the penetrating type, which shows a marked downward growth. The diagram suggests that occult carcinoma has a propensity either for longitudinal growth along the bronchial lumen or for transmural growth into the bronchial wall at the time of occurrence. It is likely that the penetrating type grows rapidly and becomes advanced in a short time. Identification of longer lesions of the creeping type is occasionally problematical both at bronchoscopy and at surgical treatment. The stump is usually positive for carcinoma unless frozen sections or imprint specimens of the margin of resection are examined, because it is frequently difficult to identify the proximal end of extension by bronchoscopy. PMID- 2909195 TI - The prostatic capsule: does it exist? Its importance in the staging and treatment of prostatic carcinoma. AB - Pathologic evaluation of tumor extent in a radical prostatectomy specimen for prostatic adenocarcinoma is extremely important in staging and planning further therapy. We studied whole-organ sections of 50 prostate glands, obtained at either radical prostatectomy for adenocarcinoma or cystoprostatectomy for bladder cancer, to evaluate the so-called capsule of the prostate, the prostatic apex, and the surgical margins. The outer surface of the prostatic portion of the specimen was totally inked with different colors for the anterior, posterior, left, and right areas. Cross sections were processed for histologic examination, and the apex (distal 1.5 cm) was amputated and radially sectioned (like a cervical cone). We found that the "capsule" is made up of a band of concentrically placed fibromuscular tissue that is an inseparable component of the prostatic stroma. The outer surface of this tissue gives rise to a few bundles of fibromuscular stroma that penetrate and disappear into the periprostatic connective tissue stroma. The apex is sparse in glandular elements, particularly in the anterior portion, and the outer fibromuscular layer is no longer present. Thus we conclude that the prostate does not have a true capsule, but only an outer fibromuscular band. PMID- 2909196 TI - Deep penetrating nevus. AB - We report a clinical and histologic study of 70 patients, each with a single melanocytic lesion termed "deep penetrating nevus" (DPN). The lesions are most commonly found on the face, upper trunk, or proximal extremities of patients between the ages of 10 and 30 years. Typically they are darkly pigmented. Histologically they are characterized by loosely organized nests of pleomorphic pigmented cells that penetrate deep into the reticular dermis and often to the subcutaneous fat. Follow-up was obtained from 48 patients. It ranged from 1 to 23 years (mean, 7 years). Despite an initial histologic diagnosis of malignant melanoma in 29% of the cases, there were no local recurrences and no distant metastases. It is important to differentiate DPN from malignant melanoma. The characteristic histologic features of DPN also allow its differentiation from spindle cell and epithelioid cell nevi and blue nevi. PMID- 2909197 TI - Multiple branchial cleft-like cysts in Hashimoto's thyroiditis. AB - We report two cases of multiple intrathyroidal cysts in women with Hashimoto's thyroiditis. The cysts were lined by squamous and focally columnar epithelium, and they were surrounded by follicular lymphoid tissue and a fibrous capsule. They appeared similar to branchial cleft cysts of the lateral neck and were distinct from previously reported types of thyroid cysts. Although the histogenesis of these lesions is unclear, they are probably derived from developmental rests. A relationship between the cystic enlargement of these rests and the Hashimoto's disease seems likely. PMID- 2909198 TI - Serous cystadenocarcinoma of the pancreas: a new entity? AB - Microcystic cystadenoma of the pancreas is a well-recognized although rare pathological entity. All previously reported examples of this tumor have been uniformly benign in behavior. In this case report, we present a primary tumor of the pancreas that was histologically indistinguishable from microcystic adenoma, but which behaved in a malignant fashion. Metastases were found in the stomach and liver. We believe that this case represents a new entity, which we have termed "serous cystadenocarcinoma of the pancreas." PMID- 2909199 TI - C-cell hyperplasia of the thyroid in a patient with goitrous hypothyroidism and Hashimoto's thyroiditis. AB - A 63-year-old man with a goiter and primary hypothyroidism due to Hashimoto's thyroiditis was found to have hypercalcitonemia and, though hypothyroid, markedly elevated serum total and free T3 levels. The latter findings were attributable to circulating T3 autoantibodies and interference with radioimmunoassay. An infusion of calcium and pentagastrin resulted in abnormal increases in serum calcitonin levels. Because there was no evidence of a nonthyroidal cause for the hypercalcitonemia, the patient had a total thyroidectomy. Pathological examination of the thyroidectomy specimen revealed typical Hashimoto's thyroiditis and extensive C-cell hyperplasia symmetrically distributed throughout the upper and middle thirds of each lobe. The C cells stained strongly with immunoperoxidase stains for calcitonin, chromogranin, and CEA using absorbed polyclonal anti-CEA antibody. Less extensive staining for CEA was obtained using the monoclonal antibodies for CEA, 374/14, 250/183, and 431/31; only a few reactive cells were noted using 431/31. Postoperatively, serum calcitonin levels fell to normal and did not rise with a repeat calcium-pentagastrin infusion test. This patient appears to be the first instance of C-cell hyperplasia associated with Hashimoto's thyroiditis, while elsewhere an association with medullary thyroid carcinoma has been reported. These observations raise questions regarding a possible pathogenetic relationship between Hashimoto's thyroiditis and C-cell neoplasia. PMID- 2909200 TI - Capillaritis and pulmonary hemorrhage in Wegener's granulomatosis. PMID- 2909201 TI - Tall cell papillary carcinoma. PMID- 2909203 TI - Hypersensitivity pneumonitis treated with an electrostatic dust filter. AB - A 60-year-old woman had had recurrent acute migratory pneumonias for 9 months. The results of an evaluation, which included tests for serum precipitins, a transbronchial biopsy, and a bronchial provocation, confirmed a diagnosis of hypersensitivity pneumonitis caused by an Aspergillus species. The findings from gravity air cultures in the home showed a heavy infestation of mold. The installation of electrostatic dust filters in the return ducts of the central air conditioning system resulted in the lowering of mold colony counts to normal levels. This change in the environment enabled the patient to live at home without having the signs and symptoms of hypersensitivity pneumonitis, or a need for medication. Thirty months after the electrostatic dust filters were installed, total mold colony counts were still normal, the patient remained free of the signs and symptoms of hypersensitivity pneumonitis, and serum precipitins could no longer be demonstrated. The results of a bronchial challenge to Aspergillus species, however, remained positive; these positive results suggest that long-term memory immune mechanisms may play an important role in the pathogenesis of hypersensitivity pneumonitis and lessen the importance of precipitins in establishing a diagnosis. We report that electrostatic dust filters may be an effective treatment for patients with hypersensitivity pneumonitis when avoidance of the causative antigen cannot be easily and rapidly achieved. PMID- 2909202 TI - Recombinant human erythropoietin treatment in pre-dialysis patients. A double blind placebo-controlled trial. AB - STUDY OBJECTIVE: To determine the efficacy and safety of recombinant human erythropoietin (r-HuEPO) in predialysis renal patients. DESIGN: Randomized, double-blind, placebo-controlled trial for 8 weeks. SETTING: Inpatient and outpatient facility in the Clinical Research Center of a university-based hospital. PATIENTS: Fourteen adult subjects with renal insufficiency (mean serum creatinine, 473 mumol/L +/- 61 [6.2 +/- 0.8 mg/dL]) and anemia (mean hematocrit, 0.27 +/- 0.01). INTERVENTIONS: Recombinant human erythropoietin, 50, 100, or 150 IU/kg body weight or placebo given intravenously three times per week. MEASUREMENTS AND MAIN RESULTS: Subjects who received active r-HuEPO showed a dose dependent rise in hematocrit; mean hematocrit increased 41% from 0.27 +/- 0.01 to 0.38 +/- 0.01. At the same time, erythrocyte mass rose 43% from 13.7 +/- 0.6 mL/kg in the baseline state to 19.6 +/- 1.0 mL/kg after treatment. Maximal oxygen consumption during exercise increased 9% from 16.0 mL/min.kg +/- 1.8 to 17.5 mL/min.kg +/- 1.9. CONCLUSIONS: Recombinant human erythropoietin is effective and safe in ameliorating the anemia of pre-dialysis patients. PMID- 2909204 TI - Cardiovascular and renal toxicity of a nonionic radiographic contrast agent after cardiac catheterization. A prospective trial. AB - STUDY OBJECTIVE: To determine the incidence of cardiovascular and renal toxicity of a nonionic contrast agent when used for cardiac catheterization, and to assess the value of electrolytes and urinalysis results as predictors of nephropathy induced by a contrast agent. STUDY DESIGN: Nonrandomized trial using a criterion standard and a cohort analytic study with a 48-hour follow-up. SETTING: Referral based university hospital. PATIENTS: Convenience sample of patients having diagnostic cardiac catheterization. Renal function and clinical status were evaluated at baseline in 1,144 patients; at 24 hours in 1,077 (94%); and at 48 hours in 663 (57%). INTERVENTIONS: After patients received saline for hydration, coronary angiography and left ventriculography were done with iopamidol (average dose, 203 +/- 56 cc). MEASUREMENTS AND MAIN RESULTS: The definite and possible incidence of major acute cardiovascular complications from nonionic contrast media was 0.2% and 0.7%, respectively. The mean serum creatinine level increased 11.5 mumol/L from baseline at 24 hours (P less than 0.0001) and 16.8 mumol/L from baseline at 48 hours (P less than 0.0001). Results in a randomly selected training sample were studied to determine predictors of a rise in serum creatinine of 44.2 mumol/L or more. The baseline serum creatinine level and age were significant predictors of renal injury, but hypertension, diabetes mellitus, congestive heart failure, vascular disease, the volume of contrast agent injected or baseline values of urinary variables did not predict nephrotoxicity. In an independent validation sample, only the baseline serum creatinine level was confirmed as a predictor of nephrotoxicity, whereas age was not. A model that predicted contrast-induced nephropathy by the serum creatinine level showed an exponential increase in the risk for nephrotoxicity if the baseline level was 106.1 mumol/L or higher. CONCLUSIONS: Patients have a small but significant rise in serum creatinine after cardiac catheterization with a nonionic contrast agent. Baseline renal insufficiency is the only confirmed predictor of nonionic contrast induced nephrotoxicity. PMID- 2909205 TI - Health science information management and continuing education of physicians. A survey of U.S. primary care practitioners and their opinion leaders. AB - PURPOSE: To identify self-perceived problems in managing science information needs of U.S. primary practitioners and their opinion leaders. SAMPLE: A two stage random sample of the American Medical Association's "Masterlist of Physicians" to identify 625 office-based physicians, including general practice, family practice, internal medicine, obstetrics and gynecology, and pediatrics, and 100 physician opinion leaders. DATA COLLECTION: A formal telephone survey was completed for 79% of practitioners and 90% of opinion leaders sampled, using a pretested instrument applied by trained telephone surveyors. RESULTS OF DATA ANALYSIS: Both practitioners and opinion leaders claimed that published reviews were the most useful means of identifying their information needs. When asked about use of six recent clinical advances, that is, "markers," for example, hemoglobin-A1C for diabetic control, as many as one fifth to one half were not using or were not aware of such an advance. Less than 1 in 3 practitioners personally searched the literature when information was needed; 2 in 3 claimed literature volume was unmanageable; 9 of 10 practitioners and opinion leaders assessed the scientific value of literature obtained, primarily from their own experience, with less than 1 in 10 contacting research methods specialists. Respondents suggested various innovations to better manage their science information needs in the future. CONCLUSIONS: Primary practitioners require substantial help in meeting current science information needs. Increase in such resources as "validated reviews" or "expert networks" might help meet these needs. PMID- 2909206 TI - Primary bile duct lymphoma in the acquired immunodeficiency syndrome (AIDS). PMID- 2909208 TI - Myocarditis and endomyocardial biopsy. PMID- 2909209 TI - Autopsies and preventable deaths. PMID- 2909207 TI - Calcitriol in prolonged hypocalcemia due to the tumor lysis syndrome. PMID- 2909210 TI - Cocaine complications and pseudocholinesterase. PMID- 2909211 TI - Screening for diabetes mellitus. PMID- 2909212 TI - Septic arthritis in hemophilic patients and infection with human immunodeficiency virus (HIV) PMID- 2909213 TI - Treating disseminated Mycobacterium avium-intracellulare infection. PMID- 2909214 TI - Ciprofloxacin and delirium. PMID- 2909215 TI - Slow-release verapamil and hyperglycemic metabolic acidosis. PMID- 2909216 TI - Blood pressure screening in the workplace. PMID- 2909217 TI - Maternity and parental leave policy. PMID- 2909218 TI - Employee health practices. Relationships between attitudes, perceptions, and behaviors. PMID- 2909220 TI - Identifying a research agenda for nursing. PMID- 2909219 TI - Occupational health and safety content in baccalaureate nursing programs. PMID- 2909221 TI - Dealing with chemical dependency. PMID- 2909222 TI - Computed tomography of salivary glands in Sjogren's syndrome. AB - Three cases of Sjogren's syndrome, one with uncomplicated disease, and the other two complicated by pseudolymphoma and malignant lymphoma, respectively, are presented. Computed tomography can provide information useful in the diagnosis, detection of complications, and, therefore, management of Sjogren's syndrome. PMID- 2909223 TI - Spontaneous extracranial pneumatocele associated with mastoid hyperpneumatization. AB - Spontaneous extracranial pneumatoceles unassociated with trauma are rare. We report a case of spontaneous extracranial mastoid pneumatocele associated with exuberant pneumatization of the calvarium and mastoid. The patient presented with a compressible bulge over the base of the zygoma and superior to the pinna. Surgical exploration demonstrated a large air sac in continuity with nontraumatic bony defects of the tympanosquamous and tympanomastoid sutures. PMID- 2909224 TI - Itchy ear syndrome. PMID- 2909225 TI - Caution urged in treating 'steroid-dependent anosmia'. PMID- 2909226 TI - Pathologic quiz case 2. Leiomyosarcoma of the nasal cavity. PMID- 2909227 TI - Pathologic quiz case 1. Invasive aspergillosis of the maxillary sinus and nose. PMID- 2909228 TI - A word of caution. PMID- 2909229 TI - Sudden sensorineural hearing loss as a presentation of multiple sclerosis. AB - While auditory involvement in multiple sclerosis is not infrequent, sensorineural hearing loss as the initial manifestation of this disease is rare. Auditory brain stem evoked responses, speech audiometry, acoustic reflexes, and electronystagmography yield significant objective information concerning brain stem involvement. Magnetic resonance imaging objectively documents white matter demyelinization. The acute onset of the retrocochlear type of auditory dysfunction without other evidence of central nervous system involvement can be an early manifestation of this disease. Two patients with multiple sclerosis had sudden sensorineural hearing loss, with one patient experiencing this as the sole initial complaint. PMID- 2909230 TI - Human leukocyte antigen in childhood unilateral deafness. AB - Human leukocyte antigen frequencies were examined in 40 Japanese patients with severe unilateral sensorineural hearing loss found in childhood. Human leukocyte antigen-Bw54 was significantly increased in frequency. No statistically significant deviation in the Bw54 frequency was observed among several possible subgroups studied. Although this group of patients may have various causes, and underlying mechanism is still unclear, this preliminary study suggests that childhood unilateral deafness may be associated with a genetically determined factor(s). PMID- 2909231 TI - Middle-latency responses. I. Electrical and acoustic excitation. AB - The electrically evoked auditory brain-stem response has been used in the past to assess auditory system function with regard to cochlear prosthesis application. The brief latency of the response makes it susceptible to electrical artifact contamination, and waveform identification is often difficult. As a possible alternative for a noninvasive measure of system excitability, the middle-latency response (MLR), elicited by electrical stimulation, was investigated. Middle latency responses were recorded in response to acoustic and round-window electrical stimulation in albino guinea pigs. Acoustic and electrically evoked MLR waveforms were similar, as were their respective latency/intensity functions. Amplitude/intensity functions for the electric MLR showed greater variability than acoustically evoked MLR functions. The electric MLR is readily evoked and relatively insensitive to electrical artifact in the guinea pig. It is potentially a useful tool in assessing the integrity of auditory pathways and consequently in the development of diagnostic tests for cochlear implant candidates. PMID- 2909232 TI - Nasal symptoms associated with cocaine abuse during adolescence. AB - A questionnaire on cocaine-use patterns and associated adverse effects on the nasal passages was completed by 464 adolescents. The respondents were abusers of various nonintravenous drugs enrolled in seven modified outpatient treatment facilities for alcohol and other drug abuse in five geographic regions of the country. Three hundred thirty-six respondents (72%) noted that they had used cocaine one or more times prior to their entry into the treatment program. The 336 recovering cocaine users were divided into three groups: those who had used cocaine fewer than 25 times (203 [60%]); those who had used cocaine between 25 and 99 times (107 [32%]); and those who had used the drug daily plus at least 100 times total use of the drug (26 [8%]). Statistically, we found a highly significant difference between the first group and the other two groups for cocaine-associated symptoms, such as frequent sniffing, "sinus" problems, and diminished olfaction. Approximately 30% of those who had "snorted" cocaine at least 25 times but less than daily, vs 47% of those who used the drug daily, recalled that they had nasal membrane irritation with nasal crusts or scabs, recurrent nosebleeds, or both. The astute otolaryngologist should consider cocaine abuse as a cause of puzzling or recalcitrant rhinitis, even during teenage years. PMID- 2909233 TI - Office-based system for voice analysis. AB - There has been recent growing interest in the analysis of various electronically recorded signals as potential tools for objective assessment of vocal dysfunction. In the past, analysis of such signals required an expensive multitrack FM recorder, mainframe computer system, customized software, and significant time commitment. This report describes an adaptation of commercially available components that allow digital recording of multiple electronic signals, storage of data, and subsequent signal analysis using an inexpensive personal microcomputer system. Commercially available software for manipulation and examination signals is discussed as adapted for examination of glottographic and acoustic signals. The relatively inexpensive availability of similar computer systems will, hopefully, encourage assessment of the clinical applications of objective techniques of voice quality. PMID- 2909234 TI - Age-related changes in the internal branch of the rat superior laryngeal nerve. AB - This investigation was initiated to provide data on the ultrastructural basis for neurologic age-related changes in laryngeal sensory function. In the present study, an animal model (female Wistar rats: age range: young [Y], 3 to 5 months; old [O], 25 months; and very old [VO], 29 to 30 months) was used to examine systematically changes in the internal branch of the superior laryngeal nerve with age using electron microscopic morphometric techniques. Total fiber counts, fiber populations (size categories), and mean fiber size for myelinated and unmyelinated fibers did not change with age. Qualitative changes were consistent with segmental demyelination and axonal degeneration in the older animals. There was also a significant age-related increase in the volume fraction of adaxonal Schwann cell cytoplasm (Y, 0.019; O, 0.041; and VO, 0.042). Ultrastructural correlates of intracellular support and axonal transport showed a significant decrease in the numerical density of neurofilaments (Y, 0.126/micron2; O, 0.073/micron2; and VO, 0.078/micron2) in the older animals, but no change in the numerical density of microtubules. Energy metabolism correlates in the form of mitochondrial volume fraction did not change with age. There was a significant increase in the volume fraction of the intrafascicular extracellular space (Y, 0.224; O, 0.271; and VO, 0.301), indicating a late, age-related change in the extracellular environment. These changes could lead to decreased conduction velocity or complete fiber dysfunction. A number of these changes resembled those of aged human peripheral nerves already examined. PMID- 2909235 TI - Adenotonsillectomy. A safe outpatient procedure. AB - Traditionally, adenotonsillectomy in children and tonsillectomy in adults have been performed as inpatient procedures. Our experience with this procedure as outpatient started in 1975 at the University of Miami-Jackson Memorial Medical Center. From 1975 to 1987, 1428 cases performed in Florida and Cleveland were reviewed to evaluate the safety and efficacy of the technique used. Bismuth subgallate and epinephrine mixture for hemostasis is used without relying on electrocautery, ties, or suture technique to control bleeding. The incidence of immediate and delayed postoperative bleeding in a series of patients was extremely low (four [0.28%] of 1428 cases). Our technique has good hemostatic properties allowing vessels to contract and retract into the muscle of the tonsillar fossae and adenoid bed. Bismuth subgallate activates factor XII (Hageman factor) and, therefore, markedly accelerates the cascade of blood clotting. Outpatient adenotonsillectomy is safe, cost-effective, and minimizes psychologic implications, which may be an important factor, especially in children. Ambulatory adenotonsillectomy has not been well emphasized in the literature. PMID- 2909236 TI - Esophageal stethoscope. Another possible cause of vocal cord paralysis. AB - Hoarseness after endotracheal intubation can result from compression of the anterior branch of the recurrent laryngeal nerve as it passes behind the thyroid cartilage to innervate the lateral cricoarytenoid muscle. This usually occurs when the cuff of the endotracheal tube lies in the larynx instead of the trachea. When a nasogastric tube is positioned in the midline, resultant postcricoid inflammation can result in vocal cord immobility. This may result from neuropraxia of the posterior branch of the recurrent laryngeal nerve that innervates the posterior cricoarytenoid and interarytenoid muscles, or inflammatory spasm of the interarytenoid muscles themselves. We present a case of vocal cord paralysis after general anesthesia that may have been caused by an esophageal stethoscope. The mechanism for vocal cord immobility could be similar to that of a midline nasogastric tube with resultant postcricoid inflammation. We describe measures that can be taken to prevent vocal cord paralysis after intubation of the larynx or esophagus. PMID- 2909237 TI - Studies on DNA binding of caffeine and derivatives: evidence of intercalation by DNA-unwinding experiments. AB - Caffeine and derivatives are compounds with pleiotropic effects on the genetic material which are supposed to originate from drugs binding to DNA. Here we show, by using two different topological methods, that methylated oxypurines, at biologically relevant concentrations, unwind DNA in a fashion similar to known intercalators. Methylated oxypurines could be ranked by decreasing unwinding potency: 8-methoxycaffeine greater than 8-ethoxycaffeine greater than 8 chlorocaffeine greater than caffeine greater than theophylline. These findings confirm, with a different assay, interaction of caffeine with DNA and add additional support to an intercalative mode of binding of these drugs to DNA. PMID- 2909238 TI - Ornithine decarboxylase activity and the accumulation of its mRNA during early stages of liver regeneration. AB - The marked and well documented stimulation of hepatic ornithine decarboxylase (ODC; EC 4.1.1.17) in response to partial hepatectomy is at least to some extent attributable to an enhanced accumulation of the enzyme's mRNA. The stimulation of ODC activity was associated with an increased accumulation of two ODC-related mRNA species (2.1 and 2.6 kilobases; kb) as revealed by Northern blot hybridization analyses. The levels of the above-mentioned messages remained elevated for 6 h after partial hepatectomy, at which time the enzyme activity had returned to almost control levels. Furthermore, ODC protein levels remained relatively stable after the first peak of ODC activity, suggesting that posttranslational activity was responsible for the changes in ODC activity after the initial burst. In addition to the two mRNA species typical of mouse cells, rat tissues contained a third hybridizable message (1.6 kb). This smaller poly(A)+ RNA was never seen in samples obtained from mouse or human cells, but was always present in samples obtained from rat tissues. Interestingly this rat specific message appeared to be expressed in somewhat opposite manner to the other two mRNA species. PMID- 2909239 TI - Presence of pancreatic-type phospholipase A2 mRNA in rat gastric mucosa and lung. AB - The content of mRNA for a pancreatic-type phospholipase A2 present in rat gastric mucosa was much greater than that in pancreas. In lung the mRNA for this pancreatic-type phospholipase A2 was also detected, but less than in pancreas. Nucleotide sequence analysis showed that these pancreatic-type phospholipase A2 cDNAs derived from rat gastric mucosa and lung were completely identical to that from rat pancreas (Ohara et al. (1986) J. Biochem. 99, 733-739). This demonstrates that the pancreatic-type phospholipase A2 present in gastric mucosa and lung does not originate from pancreas. PMID- 2909240 TI - Deoxyribonuclease II purified from the isolated lysosomes of porcine spleen and from porcine liver homogenates. Comparison with deoxyribonuclease II purified from porcine spleen homogenates. AB - Porcine spleen DNase II (EC 3.1.22.1), one of the best-characterized DNases II, is subcellularly located in lysosomes because the enzyme is co-sedimented with two of the lysosomal marker enzymes, cathepsin D and acid phosphatase. The physicochemical properties, including the subunit structure, sensitivity to iodoacetate inactivation, native molecular weight and chromatographic behavior, of the DNase II purified from the isolated lysosomes of porcine spleen are indistinguishable from those of the same enzyme purified from the whole porcine spleen homogenate. DNase II can also be extracted from porcine liver with 0.05 M H2SO4 or 0.1 M NaCl and purified from either extract by a series of column chromatographies. The purified liver DNase II from either extract has the same subunit structure (alpha-chain, Mr 35,000 and beta-chain, Mr 10,000) as the purified DNase II of porcine spleen. The two liver extracts as well as the extracts of spleen and gastric mucosa contain DNase II with very similar properties on Sephadex G-100 gel filtration, on acid polyacrylamide gel electrophoresis under non-denaturing conditions, and on isoelectric focusing. The data strongly suggest that, for the same species of animal, the DNase II activities in various tissues are associated with protein molecules of identical structure. PMID- 2909241 TI - The protamine gene chromatin in developing trout testis exists in an altered state. AB - Micrococcal nuclease was used to probe the nucleosomal organization of the rainbow trout germ-line-specific protamine multi-gene family in testis and erythrocytes. In erythrocyte chromatin, the repressed protamine genes show a distinct nucleosomal repeat pattern. However, in early-stage testis chromatin, where the protamine genes are expressed, they lack a distinct nucleosomal repeat pattern, indicating that the disrupted chromatin structure is related to their transcriptional activity. Micrococcal nuclease-digested testis and erythrocyte chromatin was separated into soluble and insoluble fractions. Transcriptionally active/competent genes of testis that had been labeled by nuclear nick translation were enriched in the low-salt eluted, micrococcal nuclease-sensitive chromatin fraction. This fraction was not enriched in protamine DNA sequences. In testis, but not erythrocytes, protamine DNA sequences were slightly enriched in chromatin that fractionated with insoluble nuclear material, suggesting that transcriptionally active protamine gene chromatin has an insoluble character. Since the different protamine genes may not be simultaneously expressed, our results show the distribution of both transcriptionally active and inactive protamine genes. However, our observations indicate that the active germ-line specific protamine gene chromatin shares several, but not all, of the features associated with other active tissue-specific genes. PMID- 2909242 TI - Phosphorylation and guanine nucleotide exchange on polypeptide chain initiation factor-2 from Artemia embryos. AB - Eukaryotic initiation factor-2 (eIF-2) from Artemia embryos is able to exchange guanine nucleotides at the same rate in the presence or absence of Mg2+ when the reaction is carried out with either purified eIF-2 at 30 degrees C or less purified preparations at any temperature (10-30 degrees C). No exchange factor appears to catalyze this reaction. However, with purified eIF-2 at lower temperatures (10 degrees C) the exchange is clearly impaired by Mg2+ and this impairment is overcome by the guanine nucleotide exchange factor (GEF) of rabbit reticulocytes. Thus, Artemia eIF-2 is able to exchange guanine nucleotides by two alternative mechanisms that may reflect two states of the protein. Phosphorylation of the eIF-2 alpha subunit by the heme-controlled inhibitor (HCI) of rabbit reticulocytes abolishes the GEF-dependent reaction, but has no effect on the factor-independent one. The search for eIF-2 alpha kinases in Artemia embryo led to the detection of only one such enzyme, which was identified as a casein kinase type II. None of the exchange reactions is affected by the phosphorylation of the eIF-2 alpha subunit by this kinase, suggesting that, irrespective of the kind of mechanism for guanine nucleotide exchange that is actually operating in Artemia, it might not be a target for regulation by eIF-2 alpha phosphorylation. PMID- 2909243 TI - Interaction of DNA polymerases with phospholipids. AB - Effects of various phospholipids on the in vitro reactions of eukaryotic DNA polymerases alpha, beta and gamma were tested systematically. When phospholipids were added directly to the reaction mixture, neither stimulation nor inhibition was produced. However, when phospholipids were preincubated with enzymes in the absence of template-primer, some of them showed strong inhibition. Cardiolipin strongly inhibited the reactions of all three DNA polymerases and also of terminal deoxynucleotidyl transferase. Phosphatidylinositol selectively inhibited the reaction of DNA polymerase gamma. Phosphatidic acid moderately inhibited DNA polymerase alpha and strongly inhibited DNA polymerase gamma. The inhibition of DNA polymerase gamma by cardiolipin was nearly competitive with template-primer. Since the inhibition was reversed by the addition of 0.05% Triton-X 100 during preincubation, the phospholipid might interact with enzyme protein at the hydrophobic region in competition with template-primer. These results suggest a possible involvement of phospholipids in DNA replication in mitochondria and in nucleus through interaction with DNA polymerase. PMID- 2909244 TI - Carbamoylcholine-induced accumulation of inositol mono-, bis-, tris- and tetrakisphosphates in isolated cardiac myocytes from adult rats. AB - The effect of carbamoylcholine on the phosphoinositide cycle in isolated ventricular myocytes from adult rats was studied. Separation of the phosphoinositides by high-performance thin-layer chromatography showed a constant ratio of incorporation of myo-[2-3H]inositol into phosphatidylinositol, phosphatidylinositol 4-monophosphate and phosphatidylinositol 4,5-bisphosphate of cultured cardiac myocytes after at least 2 h. Carbamoylcholine caused a dose dependent and time-dependent accumulation of inositol mono-, bis- and trisphosphates, which was antagonized by atropine. Using anion-exchange HPLC the existence of inositol 1,4,5-trisphosphate, inositol 1,3,4-triphosphate and inositol 1,3,4,5-tetrakisphosphate was confirmed in rat ventricular myocytes. Inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate accumulated within 20 s, while inositol 1,3,4-trisphosphate, inositol 1,4-bisphosphate and inositol monophosphate increased within 5 min. PMID- 2909245 TI - Cyclic AMP-dependent protein kinases of Paramecium. I. Chromatographic and physical properties of the enzymes from cilia. AB - The cAMP-dependent protein kinases of the cilia of the protozoan Paramecium tetraurelia were resolved and characterized. Two cAMP-dependent activities were present in cilia; the two ciliary kinases resemble types I and II from vertebrate tissues. Part of the ciliary kinase activity (primarily type II) was released by freeze-thawing, but a significant amount remained particulate. Both kinases were found as aggregates of about 220 kDa and of about 70 kDa. A portion of the cAMP binding activity in ciliary extracts separated from kinase activity, and eluted at 36 kDa during gel filtration. Photoaffinity labeling with 8-azido-cAMP identified cAMP-binding proteins of 45-52 kDa in type II kinase from cilia, and of 43-46 kDa in type I kinase. The type II kinase was apparently autophosphorylated, causing a decrease in mobility during sodium dodecyl sulfate polyacrylamide gel electrophoresis. PMID- 2909246 TI - Cyclic AMP-dependent protein kinases of Paramecium. II. Catalytic and regulatory properties of type II kinase from cilia. AB - The type II cAMP-dependent protein kinase (cAMP-PK-II) from cilia of Paramecium, purified free of type I cAMP-PK (cAMP-PK-I) and of cGMP-dependent protein kinase (cGMP-PK), phosphorylated several basic proteins and a heptapeptide containing serine (Kemptide). The enzyme was partially inhibited by the protein kinase inhibitor (Walsh inhibitor), but only at relatively high inhibitor concentrations. Half-maximal activation of cAMP-PK-II occurred at 15-25 nM cAMP. Several cAMP analogs were tested for ability to bind and activate the enzyme. 8 bromo-cGMP, a potent activator of Paramecium cGMP-PK, was a poor activator of Paramecium cAMP-PK-II. Activation of cAMP-PK-II was influenced by the phosphorylation assay buffer. Phosphate buffers provided increased activation by cAMP but decreased total activity relative to that measured in Mops-Tris buffer. The kinase was cAMP-independent when the pH of the assay buffer was high. Preincubation of cAMP-PK-II with histones also activated the enzyme in the absence of cAMP. The cAMP-PK-II bound cAMP with a Kd of 23 nM, and bound cAMP was released with a biphasic time course, suggesting two non-identical binding sites. The properties of the cAMP-PK of this ciliated protozoan appear to be closely similar to those of vertebrates. PMID- 2909247 TI - Calmodulin binding to the intestinal brush-border membrane: comparison to other calcium-binding proteins. AB - The intestinal brush-border membrane contains a high concentration of calmodulin bound to a 105,000 dalton (105 kDa) protein. Binding of radioiodinated calmodulin to this protein does not require calcium but is inhibited by trifluoperazine and excess unlabelled calmodulin. Recent evidence suggests that the 105 kDa protein in conjunction with calmodulin may be involved in the regulation of calcium transport across the brush-border membrane. In this report, we evaluated the binding of the 105 kDa protein to other radioiodinated calcium-binding proteins including the vitamin D-dependent intestinal calcium-binding protein. We observed that troponin C and S100 beta protein both bound strongly to the 105 kDa protein. The binding of S100 beta was inhibited by EGTA, but was little affected by trifluoperazine and excess unlabelled S100 beta, whereas that of troponin C was inhibited by trifluoperazine and excess unlabelled troponin C, but was little affected by EGTA. Both troponin C and S100 beta bound to a large number of proteins to which calmodulin did not bind. The vitamin D-dependent calcium binding protein (calbindin) from chick intestine and rat kidney also bound to the 105 kDa protein, albeit more weakly than troponin C, S100 beta and calmodulin. The binding of the calbindins was increased by EGTA and was little affected by trifluoperazine and excess unlabelled calbindin. Parvalbumin, rat osteocalcin, and alpha-lactalbumin showed little binding to any brush-border membrane protein. Our results indicate that the 105 kDa calmodulin-binding protein of the intestinal brush border can bind to a variety of calcium-binding proteins all of which contain homologous regions thought to be the calcium-binding sites. Only the binding of troponin C resembles the binding of calmodulin, however, in being inhibited by trifluoperazine and excess unlabelled ligand. The functional significance of these observations in terms of regulating calcium transport across the brush-border membrane remains to be established. PMID- 2909248 TI - A growth-promoting factor for human myeloid leukemia cells from horse serum identified as horse serum transferrin. AB - A growth-promoting factor for human myeloid cells was purified to apparent homogeneity from horse serum by a combination of gel filtration, blue Sepharose affinity chromatography, Mono Q anion-exchange chromatography, Mono P chromatofocusing and sodium dodecyl sulfate polyacrylamide gel electrophoresis. The growth promoter was an iron-bound, single glycopolypeptide chain with a molecular weight of 84,000, an isoelectric point of 5.4 and an amino terminal sequence of Glu-Gln-Thr-Val-Arg-Trp-Cys-Thr-Val-Ser-Asn-His-Glu-Val-Ser-Lys-. According to the results of the amino acid sequence, iron binding ability and physicochemical properties, we identified the growth-promoting factor as horse serum transferrin. It was highly active in promoting the proliferation of a human monocytic leukemia cell line, THP-1, as well as of two other human myeloid cell lines, HL-60 and K-562. It had the same activity in proliferating THP-1 cells as 5% fetal calf serum-supplemented medium. Horse serum transferrin could be substituted for human or bovine serum transferrin. PMID- 2909249 TI - Biosynthesis and clearance of prothrombin in warfarin-treated rats. AB - The steady-state concentration of abnormal plasma prothrombin in warfarin-treated rats (10 mg/kg) was found to be approx. 6% of the plasma prothrombin level in normal rats. The clearance of abnormal plasma prothrombin in warfarin-treated rats was studied using either cycloheximide, to inhibit the synthesis, or vitamin K, to block the appearance of abnormal prothrombin in plasma. The clearance of abnormal plasma prothrombin corresponded to a half-life of approx. 6 h, which is similar to the half-life of normal plasma prothrombin. The de novo synthesis of prothrombin in warfarin-treated and normal rats was compared by measuring the incorporation of [3H]leucine into plasma prothrombin 90 min after an intravenous injection of the isotope. In warfarin-treated rats, accumulated prothrombin precursor was carboxylated and transported into circulation by injecting vitamin K 30 min after isotope administration. On comparing the incorporation of [3H]leucine into plasma prothrombin in warfarin-treated and normal rats, no significant difference in the de novo synthesis was detected. Our results suggest that the secretion of prothrombin in warfarin-treated rats is decreased to 6% of the normal rate. As the de novo synthesis is not affected by warfarin treatment, more than 90% of the newly synthesized prothrombin appears to be degraded intracellularly. PMID- 2909250 TI - Dielectric properties of mouse lymphocytes and erythrocytes. AB - In order to study the effect of the nucleus on dielectric behavior of the whole cell, permittivity (dielectric constant) and conductivity of mouse lymphocytes and erythrocytes were measured over a frequency range from 0.1 to 250 MHz. Erythrocytes (spherocytes) showed a single dielectric dispersion, which was explained by a single-shell model that is a conducting sphere covered with a thin insulating shell. On the other hand, lymphocytes showed a broad dielectric dispersion curve which was composed of two subdispersions. The high-frequency subdispersion, which was not found for erythrocytes, was assigned to the Maxwell Wagner dispersion of the nucleus occupying about 65% of the total cell volume. Analysis of the lymphocyte dispersion was carried out by a double-shell model, in which a shelled sphere, i.e., nucleus, is incorporated into the single-shell model. The following electrical parameters were consequently estimated; the capacitance of the plasma membrane, 0.86 microF.cm-2; the conductivity of the cytoplasm, 3.2 mS.cm-1; the capacitance and conductance of the nuclear envelope are, respectively, 0.62 microF.cm-2 and 15 S.cm-2, and the permittivity and conductivity of the nucleoplasm are 52 and 13.5 mS.cm-1. PMID- 2909251 TI - Use of formycin B as a general substrate for measuring facilitated nucleoside transport in mammalian cells. AB - Formycin B, a C-nucleoside analog of inosine, is not catabolized by human erythrocytes and mouse P388 leukemia cells and is only very inefficiently phosphorylated in these cells. This relative inertness allows the measurement of its transport into and out of the cells uncomplicated by metabolic conversions. We have measured the zero-trans and equilibrium exchange flux of formycin B in these cells by rapid kinetic techniques. The Michaelis-Menten constants and maximum velocities for formycin B transport in both types of cell were similar to those previously reported for uridine and thymidine. Nevertheless, the differential mobility of the substrate-loaded and empty carrier of human erythrocytes was less for formycin B than uridine as substrate. Formycin B influx was inhibited by other nucleosides in accordance with their affinities for the carrier, but unaffected by purines. The inhibition of formycin B influx by nitrobenzylthioinosine and dipyridamole was also identical to that observed with uridine as substrate (IC50 = 10 and 30 nM, respectively). Formycin B accumulated in both types of cell to 30-40% higher concentrations than were present in the medium. This concentrative accumulation was not due to active transport, metabolism or partitioning into membrane lipids. It seems to reflect binding of formycin B to intracellular components, but does not interfere significantly with measurements of its transport. PMID- 2909252 TI - Mechanism of action of the antimitotic drug 2,4-dichlorobenzyl thiocyanate: alkylation of sulfhydryl group(s) of beta-tubulin. AB - The compound, 2,4-dichlorobenzyl thiocyanate (DCBT) was previously shown to cause mitotic arrest, disruption of intracellular microtubules, and inhibition of tubulin polymerization, with resistance to the drug conferred by a mutation in a beta-tubulin gene (Abraham, I., Dion, R.L., Duanmu, C., Gottesman, M.M. and Hamel, E. (1986) Proc. Natl. Acad. Sci. USA 83, 6839-6843). We have now examined its mechanism of action in further detail and conclude that DCBT acts as a sulfhydryl alkylating reagent. A mixed disulfide forms between the 2,4 dichlorobenzyl mercaptan moiety of DCBT and protein sulfhydryl groups with release of cyanate anion to the medium. Gel filtration and dialysis of complexes of tubulin formed with either [nitrile-14C]DCBT, [35S]DCBT or [benzyl-3H]DCBT demonstrated persistent association of 35S and 3H with denatured tubulin, but no binding of 14C to the protein even under native conditions. With equimolar tubulin and DCBT, beta-tubulin is the predominant alkylated species. At high drug concentrations, superstoichiometric amounts of DCBT react with tubulin, and both subunits are alkylated almost equally. When extracts of drug-treated L1210 murine leukemia cells were examined by polyacrylamide gel electroporesis, we found that multiple proteins were alkylated by DCBT, but the most prominent radiolabeled band was that corresponding to beta-tubulin. Dithiothreitol partially reverses inhibition of tubulin polymerization by DCBT and removes almost all the 2,4 dichlorobenzyl mercaptan moiety covalently bound to tubulin. Mitotic arrest occurs with DCBT because tubulin is the cellular protein most sensitive to the agent, probably because of its high cysteine content (20/mol). PMID- 2909253 TI - Expression of glyoxalase, glutathione peroxidase and glutathione S-transferase isoenzymes in different bovine tissues. AB - (1) The tissue-specific expression of various glutathione-dependent enzymes, including glutathione S-transferase (GST), glutathione peroxidase and glyoxalase I, has been studied in bovine adrenals, brain, heart, kidney, liver, lung and spleen. Of the organs studied, liver was found to possess the greatest GST and glyoxalase I activity, and spleen the greatest glutathione peroxidase activity. The adrenals contained large amounts of these glutathione-dependent enzymes, but significant differences were observed between the cortex and medulla. (2) GST and glyoxalase I activity were isolated by S-hexylglutathione affinity chromatography. Glyoxalase I was found in all the organs examined, but GST exhibited marked tissue-specific expression. (3) The alpha, mu and pi classes of GST (i.e., those that comprise respectively Ya/Yc, Yb/Yn and Yf subunits) were all identified in bovine tissues. However, the Ya and Yc subunits of the alpha class GST were not co-ordinately regulated nor were the Yb and Yn subunits of the mu class GST. (4) Bovine Ya subunits (25.5-25.7 kDa) were detected in the adrenal, liver and kidney, but not in brain, heart, lung or spleen. The Yc subunit (26.4 kDa) was expressed in all those organs which expressed the Ya subunit, but was also found in lung. The mu class Yb (27.0 kDa) and Yn (26.1 kDa) subunits were present in all organs; however, brain, lung and spleen contained significantly more Yn than Yb type subunits. The pi class Yf subunit (24.8 kDa) was detected in large amounts in the adrenals, brain, heart, lung and spleen, but not in kidney or liver. (5) Gradient affinity elution of S-hexylglutathione Sepharose showed that the bovine proteins that bind to this matrix elute in the order Ya/Yc, Yf, Yb/Yn and glyoxalase I. (6) In conclusion, the present investigation has shown that bovine GST are much more complex than previously supposed; Asaoka (J. Biochem. 95 (1984) 685-696) reported the purification of mu class GST but neither alpha nor pi class GST were isolated. PMID- 2909254 TI - Parameters controlling the kinetics of ferric and ferrous hemeproteins reduction by hydrated electrons. AB - To clarify the processes of hemeproteins reduction, three classes of these proteins (ferric, ferrous and desFe) were reduced by hydrated electrons generated by pulse radiolysis. Spectral and kinetic investigations were made on alpha hemoglobin chain and myoglobin. Human alpha chain has been chosen to avoid all ferric contaminations and horse ferric myoglobin to eliminate all ferrous protein fractions. We have successively studied the influences of: the iron presence, its oxidation state (II and III), the protein charge and the iron-ligand nature (H2O, OH-, N3- and CN-). For alpha human hemoglobin chain without metallic ion or with ferrous iron, the reduction rates are the same: 1.1 +/- 0.2.10(10) M-1.s-1. In the case of horse ferric myoglobin, the reduction rates depend principally on the protein charge (from pH 6.3 to pH 9.5, the reduction rate of Mb(FeIII)N3- decreases from 2.5 +/- 0.5.10(10) M-1.s-1 to 1.2 +/- 0.2.10(10) M-1.s-1) and are also modulated by the equilibrium constant of the hemeprotein-ligand association (1.2 +/- 0.2.10(10) M-1.s-1 for Mb(FeIII)N3- and 0.8 +/- 0.2.10(10) M-1.s-1 for Mb(FeIII)CN-, at pH 9.8). PMID- 2909255 TI - Pre-steady-state kinetic study on the formation of compound I and II of ligninase. AB - The reaction between ligninase and hydrogen peroxide yielding Compound I has been investigated using a stopped-flow rapid-scan spectrophotometer. The optical absorption spectrum of Compound I appears different to that reported by Andrawis, A. et al. (1987) and Renganathan, V. and Gold, M.H. (1986), in that the Soret maximum is at 401 nm rather than 408 nm. The second-order rate constant (4.2.10(5) M-1.s-1) for the formation of Compound I was independent of pH (pH 3.0 6.0). In the absence of external electron donors, Compound I decayed to Compound II with a half-life of 5-10 s at pH 3.1. The rate of this reaction was not affected by the H2O2 concentration used. In the presence of either veratryl alcohol or ferrocyanide, Compound II was rapidly generated. With ferrocyanide, the second-order rate constant increased from 1.9.10(4) M-1.s-1 to 6.8.10(6) M 1.s-1 when the pH was lowered from 6.0 to 3.1. With veratryl alcohol as an electron donor, the second-order rate constant for the formation of Compound II increased from 7.0.10(3) M-1.s-1 at pH 6.0 to 1.0.10(5) M-1.s-1 at pH 4.5. At lower pH values the rate of Compound II formation no longer followed an exponential relationship and the steady-state spectral properties differed to those recorded in the presence of ferrocyanide. Our data support a model of enzyme catalysis in which veratryl alcohol is oxidized in one-electron steps and strengthen the view that veratryl alcohol oxidation involves a substrate-modified Compound II intermediate which is rapidly reduced to the native enzyme. PMID- 2909256 TI - Investigation of the active center of rat pancreatic elastase. AB - We have isolated rat pancreatic elastase I (EC 3.4.21.36) using a fast two-step procedure and we have investigated its active center with p-nitroanilide substrates and trifluoroacetylated inhibitors. These ligands were also used to probe porcine pancreatic elastase I whose amino acid sequence is 84% homologous to rat pancreatic elastase I as reported by MacDonald, et al. (Biochemistry 21, (1982) 1453-1463). Both proteinases exhibited non-Michaelian kinetics for substrates composed of three or four residues: substrate inhibition was observed for most enzyme substrate pairs, but with Ala3-p-nitroanilide, rat elastase showed substrate inhibition, whereas porcine elastase exhibited substrate activation. With most of the longer substrates, Michaelian kinetics were observed. The kcat/Km ratio was used to compare the catalytic efficiency of the two elastases on the different substrates. For both elastases, occupancy of subsite S4 was a prerequisite for efficient catalysis, occupancy of subsite S5 further increased the catalytic efficiency, P2 proline favored catalysis and P1 valine had an unfavorable effect. Rat elastase has probably one more subsite (S6) than its porcine counterpart. The rate-limiting step for the hydrolysis of N succinyl-Ala3-p-nitroanilide by rat elastase was essentially acylation, whereas both acylation and deacylation rate constants participated in the turnover of this substrate by porcine elastase. For both enzymes, trifluoroacetylated peptides were much better inhibitors than acetylated peptides and trifluoroacetyldipeptide anilides were more potent than trifluoroacetyltripeptide anilides. A number of quantitative differences were found, however, and with one exception, trifluoroacetylated inhibitors were less efficient with rat elastase than with the porcine enzyme. PMID- 2909258 TI - The ethics of physician-pharmaceutical company relationships. PMID- 2909257 TI - Inactivation of chicken liver mevalonate 5-diphosphate decarboxylase by sulfhydryl-directed reagents: evidence of a functional dithiol. AB - Chicken liver mevalonate 5-diphosphate decarboxylase (ATP:(R)-5 diphosphomevalonate carboxy-lyase (dehydrating), EC 4.1.1.33) is inactivated by methylmethanethiosulfonate and 5,5'-dithiobis(2-nitrobenzoate). The presence of the substrates ATP or mevalonate 5-diphosphate protect very effectively against inactivation. The inactivation is second order with respect to methylmethanethiosulfonate, with an inactivation rate constant of (7.6 +/- 0.1).10(-5) microM-2.s-1, implying that the modifier may be reacting with more than one thiol in the enzyme. The enzyme is also inactivated by a number of dithiol-specific reagents, suggesting the presence of a functional dithiol. The determined pKapp values for enzyme modification by methyl methanethiosulfonate and phenylarsine oxide are 7.3 +/- 0.1 and 7.6 +/- 0.3, respectively. From the data presented, it is concluded that the enzyme possesses a functional dithiol that is important for substrate binding. PMID- 2909260 TI - Choosing interns: an exercise in frustration. PMID- 2909259 TI - Medical dramas and the press: who benefits from the coverage? PMID- 2909261 TI - Not always on the level. PMID- 2909262 TI - The use of vitamin K in the perinatal period. PMID- 2909263 TI - Prenatal care: a comparative evaluation of nurse-midwives and family physicians. PMID- 2909264 TI - The Hippocratic Oath. PMID- 2909265 TI - Double-blinding in clinical trials. PMID- 2909266 TI - Treatment of parasitic infections: Canadian versus US recommendations [correction]. PMID- 2909267 TI - Fatigue and stress in medical students, interns and residents: it's time to act! PMID- 2909268 TI - Fatigue and concerns about quality of care among Ontario interns and residents. AB - In postgraduate medical training the heavy and irregular workloads are thought to result in fatigue and a potential decrease in the quality of care provided by interns and residents. We investigated these concerns among Ontario interns and residents. Information from 1805 house staff in all specialties and different years of postgraduate education suggested a relation between hours of work, fatigue and concerns about the quality of care. PMID- 2909269 TI - User's guide for self-monitoring of capillary blood glucose levels. PMID- 2909270 TI - The use of family medical practices by patients with drinking problems. AB - The annual rate of consultation with family physicians was compared between 108 problem drinkers and a matched group of control subjects; the first group contacted physicians about twice as often as the second one, especially because of psychosocial problems and acute injuries. However, this increased rate among the problem drinkers was also due to a higher prevalence of other health-related problems for which they sought care at least once. The results are discussed in terms of the need for more definitive interventions to identify alcohol abusers, to decrease their consumption and to improve their psychosocial and physical status. PMID- 2909271 TI - Hereditary site-specific colon cancer in a Canadian kindred. AB - A large kindred with colorectal cancer unaccompanied by polyposis coli and characterized by autosomal dominant inheritance has been identified in eastern Canada. Ten family members from three successive generations have presented 17 documented colorectal cancers. The clinical features of the kindred are characteristic of hereditary site-specific colon cancer (HSSCC) (Lynch syndrome I): absence of multiple polyposis, autosomal dominant inheritance, onset of colorectal cancer at an early age and a high incidence of synchronous and metachronous colorectal cancers. A unique feature of this family is the high incidence of sporadic adenomatous polyps in affected members and their relatives. Patients with HSSCC have been managed by means of segmental colectomy followed by annual colonoscopic surveillance. All five patients with localized (Dukes' stage A or B) cancer at initial diagnosis were alive and free of disease after 2 to 12 years of follow-up, although three had required further colonic resection for metachronous carcinomas. Five young family members without cancer have had sporadic adenomatous polyps removed and are being followed with annual colonoscopy. It is not known whether polypectomy will alter the subsequent incidence of colon cancer. Subtotal colectomy is recommended for patients with HSSCC because of the high incidence of multiple lesions. An aggressive screening protocol, including colonoscopy, is recommended for all adult first- and second degree relatives of patients with HSSCC. Identification of a biomarker, which is currently being sought in this kindred, would help identify those at greatest risk of development of cancer and allow earlier intervention. PMID- 2909272 TI - The search for a safer pertussis vaccine. PMID- 2909273 TI - System helps would-be interns, hospitals lose that long-distance feeling. PMID- 2909274 TI - Latest enrollment statistics indicate Canada will be producing fewer new MDs. PMID- 2909275 TI - A CMA position. Acquired immunodeficiency syndrome. AB - The following general principles serve as guidelines for various bodies, health care professionals and the general public. Specific aspects of infection with human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) that relate to physicians' ethical responsibilities as well as society's moral obligations are discussed. Such matters include the need for education, research and treatment resources; the patient's right to investigation and treatment and to refusal of either; the need to obtain the patient's informed consent; the right to privacy and confidentiality; the importance of infection control; and the right to financial compensation in the case of occupational exposure to HIV. PMID- 2909276 TI - Family physician in a box: a software review. PMID- 2909277 TI - On the outside, looking in. PMID- 2909278 TI - Canada one country among many grappling with MD-oversupply issue. PMID- 2909279 TI - New registry allows FPs to refer obstetrical patients to other FPs. PMID- 2909280 TI - Winnipeg suffered second chancroid outbreak, team reports. PMID- 2909281 TI - Pharmacokinetics of bestatin and oral activity for treatment of experimental metastases. AB - Bestatin is a low molecular weight aminopeptidase inhibitor originally isolated from culture filtrates of Streptomyces olivoreticuli. The serum pharmacokinetics in mice are dependent on route of administration, with a short t1/2 (1.69 min t1/2 alpha and 12.8 min t1/2 beta), but a high initial serum level following i.v. administration. When administered via the i.p., s.c., i.m., or p.o. routes of administration, bestatin had serum t1/2 beta s of 8.56, 16.91, 19.25, or 15.4 min, respectively. The maximum area under the curve (concentration X time) occurred following i.v. and i.m. administration, with a lower level following p.o. or i.p. administration. Bestatin had therapeutic activity for experimental metastases, not only following i.v., i.p., and i.m. routes of administration but also following oral administration. Because of its brief serum t1/2, bestatin's therapeutic activity depends on aggressive (either daily or twice daily injection, especially following p.o. administration) and high-dose administration. Thus, the rate-limiting aspect of bestatin's therapeutic activity appears to be associated with its pharmacokinetics. PMID- 2909282 TI - Comparative effect of rat and fetal calf serum on measurement of the natural tumoricidal activity of rat lymphocytes, macrophages and polymorphonuclear cells. AB - The effect of rat serum versus fetal calf serum on the in vitro natural cytolytic activity of rat lymphocytes, macrophages and polymorphonuclear cells against syngeneic tumour cells was compared. The cytolysis level mediated by the three varieties of effector cells was lower when rat serum was used instead of fetal calf serum to supplement the culture medium. This could explain in part the discrepancies found between in vitro and in vivo studies. PMID- 2909283 TI - Inhibition of murine hepatic tumor growth by liposomes containing a lipophilic muramyl dipeptide. AB - We have investigated the ability of liposomes containing a lipophilic muramyl dipeptide, N-acetylmuramyl-L-alanyl-D-isoglutamine glycerol dipalmitate (MDP-GDP) to activate Kupffer cell tumoricidal activity in situ and to inhibit the growth of experimental hepatic micrometastases of tumor cell line H-59, a liver-homing variant of the Lewis lung carcinoma. Liposomes prepared from distearoylphosphatidylcholine/dimyristoylphosphatidylglycerol (DSPC/DMPG) and containing MDP-GDP (1 mumol and 2 micrograms, respectively) were efficiently taken up by the liver after i.v. administration. A single i.v. injection of DSPC/DMPG liposomes containing MDP-GDP was capable of inducing Kupffer cell tumoricidal activity against H-59 tumor cells as measured in vitro. Control liposomes or 100 micrograms free MDP were ineffective in inducing Kupffer cell tumoricidal activity in situ. Two treatment regimens were evaluated in vivo: firstly, C57BL/6 mice were injected with tumor cell line H-59 and subsequently treated with multiple injections of liposomal MDP-GDP. Secondly, treatment with liposomal MDP-GDP was initiated prior to tumor cell injection and continued after tumor cell injection. The ability of liposomes containing MDP-GDP to reduce the number of hepatic micrometastases using the first protocol was related to the tumor cell inoculum, significant inhibition being observed at lower liver tumor burdens (less than 25 tumor nodules). Pretreatment of the mice prior to tumor cell challenge followed by treatment afterwards greatly enhanced the efficacy of liposomal MDP-GDP and brought about a highly significant inhibition of the growth of experimental metastases even at high liver tumor burdens (greater than 50 nodules). PMID- 2909284 TI - Melanin synthesis and the action of L-dopa and 3,4-dihydroxybenzylamine in human melanoma cells. AB - The toxicity and selectivity of 3,4-dihydroxybenzylamine (DHBA), an experimental antimelanoma agent that cannot enter the melanin pathway, broadly paralleled that of L-dopa in a panel of human melanoma cell lines sensitive or resistant to the latter drug. A human retinoblastoma cell line was found to be sensitive to both compounds. The toxicity and selectivity of both catechols were associated with inhibition of DNA synthesis; DHBA was more potent yet allowed a much greater degree of recovery compared with an equitoxic level of dopa. Dopa and DHBA had similar, dose-dependent effects on the cell cycle, arresting cells in S phase at low doses and in G1 at high doses. Replication of the DNA virus adenovirus was found to be inhibited by both agents. There was no difference between sensitive and resistant cell lines in the manganese or copper/zinc forms of superoxide dismutase, or in iron content and iron-binding capacity. Catechol toxicity was inhibited by the hydrogen peroxide scavenging agents pyruvate and methaemoglobin. Sensitivity to catechols did not correlate with melanin or tyrosinase content, rate of incorporation of tyrosine or dopa, intracellular levels of phenylalanine or tyrosine, or binding of a new monoclonal antibody directed against a melanosomal protein. These results indicate that DHBA and dopa exhibit selective toxicity for neural crest tumor cells independently of the melanisation pathway and of the superoxide scavenging system. PMID- 2909285 TI - Synthesis and antitumor activity of a series of (aminoethylpyrrolidine) platinum complexes. AB - A series of aminoethylpyrrolidine-platinum complexes were synthesized and partially characterized for chemical structure. The leaving groups in this series of complexes were varied in an attempt to identify cytotoxic, water-soluble aminoethylpyrrolidine-platinum complexes. The cytotoxic activity was tested in vitro against L1210 cells sensitive to cis-diamminedichloroplatinum(II) (L1210/0), L1210 cells resistant to cis-diamminedichloroplatinum(II) (L1210/DDP), and L1210 cells resistant to 1,2-diaminocyclohexane platinum (L1210/DACH). The complexes were also tested for in vivo antitumor activity against L1210/0 cells injected i.p. The results of these studies indicate that the aminoethylpyrrolidine-platinum complexes have moderate antitumor activity but are cross-resistant in L1210/DDP cells. The degree of antitumor activity was dependent on the characteristic leaving group of a given complex. PMID- 2909286 TI - Association of sorcin with drug resistance in L1210 cells. AB - L1210 sublines independently selected for resistance to teniposide (VM-26), etoposide (VP-16), doxorubicin (DOX), dactinomycin (DACT), or vincristine (VCR) express an anionic, 22-kDa protein that is not observed in extracts of parental L1210 cells. Antibody raised against sorcin, an acidic calcium-binding protein overproduced in many other cells resistant to these agents, cross-reacts with the 22-kDa polypeptide. The levels of the 22-kDa protein (sorcin) increase with the relative levels of drug resistance of the L1210 sublines. The appearance of sorcin in these various sublines further supports the notion that the overproduction of this protein is related to the general phenomenon of multidrug resistance rather than to specific drug resistance and that selection for resistance to teniposide produces L1210 sublines with multidrug resistance. PMID- 2909287 TI - Hydroxyurea potentiation of the antineoplastic activity of cyclophosphamide and 4'-(9-acridinylamino)methanesulfon-M-anisidide (AMSA) in the brown Norway rat myelocytic leukemia model. AB - The activities of hydroxyurea (HU), 4'-(9-acridinylamino)methanesulfon-M anisidide (AMSA) and cyclophosphamide (CY) were examined in the brown Norway rat myelocytic leukemia model in experiments designed to determine the synergy, optimal drug sequencing, and therapeutic index of combinations of these agents. A single dose of CY or four consecutive daily doses of AMSA produced increased survival in leukemic rats, with a positive-slope dose-response curve up to the maximum tolerated dose (MTD). HU at 1/2 MTD produced a minimal antileukemic effect but significantly potentiated the antineoplastic activity of 1/2 MTD of CY or AMSA with no significant toxic death rate. Drug-sequence experiments demonstrated that maximal synergy was achieved when HU was given immediately after CY but immediately before or during AMSA administration. No significant cure rate was seen with any CY/HU or HU/AMSA sequence. The three drugs given in the sequence of CY followed 3 days later by HU and AMSA simultaneously, however, was curative in the majority of rats with advanced leukemia, whereas other sequences were more toxic or less effective. Each of the drugs in these experiments was given at 1/2 of its single-agent MTD. HU significantly potentiates the antineoplastic effect of CY and AMSA in a drug-sequence-dependent manner in this model, apparently with an improved therapeutic index. PMID- 2909288 TI - Evaluation of the effect of furosemide on ultrafilterable platinum kinetics in patients treated with cis-diamminedichloroplatinum. AB - It has been reported that furosemide can prevent platinum nephrotoxicity by dilution of the toxic drug in the tubule or by another unknown mechanism. To evaluate its influence on ultrafilterable platinum pharmacokinetics, we undertook a randomized prospective trial of cis-diamminedichloroplatinum (CDDP) (80 mg/m2 by a 20-min infusion) administered to 20 patients with hydration-induced diuresis. Ten patients received 20 mg/m2 furosemide 1 h before CDDP administration, and 10 patients received no diuretic drug. Plasma and urinary pharmacokinetics of platinum and creatinine were compared in both groups of patients. Plasma total and ultrafilterable platinum was always higher in the furosemide group. However, protein binding, urinary concentrations, cumulative urinary excretion, renal clearance and creatinine clearance/renal clearance ratio (fractional clearance) were not statistically different. Moreover, the fractional clearance was successively lower, equal and higher than one in both groups. These results suggest that: (1) furosemide probably causes water depletion leading to a rise in plasma concentrations; (2) its protection by a pharmacokinetic interaction is doubtful, since all other parameters (especially urinary parameters) are not significantly modified; (3) renal clearance and fractional clearance suggest a bidirectional transport of platinum in the tubule not influenced by the diuretic drug. PMID- 2909289 TI - Dominance of resistance to the alkylating agent 1,2:5,6-dianhydrogalactitol in P388 mouse lymphoma hybrid cells. AB - Cultured P388/S mouse lymphoma cells resistant to 5-bromodeoxyuridine (BUdR) and deficient in thymidine kinase (TK-) were fused with P388/DAG cells resistant to 1,2:5,6-dianhydrogalactitol (DAG), an anticancer alkylating agent, and to 6 thioguanine (6-TG) and deficient in hypoxanthine phosphoribosyl-transferase (HPRT ). Sensitivity to DAG in the hybrid line was very close to that in the P388/DAG line, which means that resistance to DAG was inherited in a quasi-dominant manner. Hybrid cells showed cross-resistance, similar to that of the DAG resistant line, to two other hexitols, dibromodulcitol (DBD) and disuccinyldianhydrogalactitol (DisuDAG). PMID- 2909290 TI - Combination chemotherapy of cisplatin and 5-fluorouracil for advanced colorectal adenocarcinoma. AB - A total of 24 patients with advanced colorectal adenocarcinoma were entered into a phase I-II study of 5-fluorouracil (5-FU) and cisplatin, 21 of whom had previously received 5-FU. The starting dose of cisplatin was 20 mg/m2 diluted in 1000 cc normal saline, given over 20 h daily for 5 days, together with 600 mg/m2 5-FU diluted in 1000 cc fluid, given simultaneously over 20 h daily for 5 days. This regiment was given every 4 weeks. The dose-limiting toxicity was renal and cumulative. All 24 patients were evaluable for toxicity. Of 12 patients on the above-mentioned starting dose, 8 underwent a cisplatin dose reduction to 15 mg/m2 due to a progressive decrease in creatinine clearance following the second or third course of treatment. Of 12 patients who started cisplatin at 15 mg/m2 and 5 FU at 600 mg/m2, 11 were maintained at this dose. A WBC nadir count of less than 2000/mm3 was seen in four patients. Thrombocytopenia occurred in three patients who received 15 mg/m2 cisplatin and 600 mg/m2 5-FU. In all, 21 of the 24 patients had objectively measurable disease and were also evaluable for response as follows: 1 complete response, 2 partial responses, 1 case of stable disease, and 17 patients with progressive disease. PMID- 2909291 TI - Phase II trial of continuous-infusion iproplatin (CHIP) and 5-fluorouracil (5-FU) in advanced colorectal carcinoma. AB - Following the observation of antitumor activity for the combination of 5 fluorouracil (5-FU) and cisplatin in metastatic colorectal carcinoma, the combination of 5-FU and iproplatin was tested, also in colorectal carcinoma, in the hope of attaining equivalent activity without the nephrotoxicity observed with 5-FU/cisplatin. However, no responses were achieved with 5-FU/iproplatin. PMID- 2909293 TI - Reactive oxygen metabolites relax the lamb ductus arteriosus by stimulating prostaglandin production. AB - To determine whether oxygen metabolites can cause ductus relaxation, we used rings of fetal ductus obtained from 36 near-term lambs and measured the effects of the oxygen metabolites generated by the combination of hypoxanthine and xanthine oxidase. The oxygen metabolites produced by hypoxanthine plus xanthine oxidase caused relaxation of the ductus that was inhibited by catalase (hydrogen peroxide scavenger) but not by superoxide dismutase (superoxide anion scavenger). In addition, hypoxanthine plus xanthine oxidase produced a 14-fold increase in prostaglandin (PG) E2 production with only twofold increase in 6-keto-PGF1 alpha (the stable metabolite of PGI2). PGE2 is the most potent relaxant of the ductus arteriosus. The presence of either catalase or indomethacin blocked both the increase in prostaglandin production and the relaxation. We conclude that reactive oxygen metabolites relax the ductus arteriosus and oppose the normal constriction that occurs after birth. However, the vasoactive effects of reactive oxygen metabolites in the ductus appear to be mediated exclusively through the generation of PGE2. PMID- 2909292 TI - The pharmacokinetics and toxicity of the anthrapyrazole anti-cancer drug CI-941 in the mouse: a guide for rational dose escalation in patients. AB - CI-941 is a new synthetic DNA-binding agent selected for phase I clinical evaluation. The drug has broad-spectrum antitumour activity against a number of murine tumours and, in contrast to doxorubicin, is unlikely to induce cardiotoxicity by a free-radical-mediated mechanism. In this study the toxicity and pharmacokinetics of CI-941 were studied in the mouse to enable the implementation of a pharmacokinetically guided dose-escalation strategy in patients. Following a single i.v. bolus injection in mice, CI-941 induced dose dependent leukopenia. The white blood cell counts were suppressed on day 3 by 18%, 50% and 65% of control, at doses of 10, 15 and 20 mg/kg CI-941, respectively. Other toxicities such as weight loss, alopecia, diarrhoea and convulsions were observed at doses greater than 20 mg/kg. Lethality studies in female Balb-c mice resulted in an LD10 value of 20 mg/kg (95% confidence limits; range, 19-21 mg/kg) and an LD50 value of 22 mg/kg (95% confidence limits; range, 21-23 mg/kg). The pharmacokinetics of CI-941 were studied at four dose levels from 1/10 of the LD10 to the LD10 (20 mg/kg). The drug was rapidly cleared from the plasma (250-400 ml/min per kg) at a rate approaching the cardiac output of mice, displaying triphasic plasma pharmacokinetics. The area under the plasma CI 941 concentration vs time curve (AUC) was linear with respect to the dose, up to and including 15 mg/kg (AUC = 110 microM x min at 15 mg/kg), but became non linear at 20 mg/kg (AUC = 277 microM x min). Despite 80%-84% plasma protein binding, CI-941 was rapidly and extensively distributed into tissues, especially the kidney. Following i.v. bolus injections at doses of 1.5 and 15 mg/kg, elimination of the parent compound by urinary excretion accounted for 12%-18% of the delivered dose. A phase-I starting dose (based on that equivalent to 1/10 of the LD10 in the mouse) of 5 mg/m2 CI-941 is recommended for single administration schedules. In addition, a pharmacokinetically guided dose-escalation strategy, based on achieving a target AUC of 110 microM x min, is proposed. PMID- 2909294 TI - Arteriolar control of capillary cell flow in striated muscle. AB - This study tests the hypothesis that capillary perfusion is controlled in groups rather than at the level of the individual capillary. We measured cell flux (using cells labeled with substituted tetramethyl rhodamine isothiocyanate, XRITC) and vessel diameter in adjoining arterioles of the terminal vasculature of hamster cremaster muscle (Nembutal, 70 mg/kg i.p.) during rest and hyperemia (10( 4) M adenosine). In terminal arterioles (TAs), 32 of 68 vessels showed cell flux increases from rest to hyperemia exceeding 25 times (i.e., 47% of TAs were relatively unperfused at rest). In vessels feeding TAs (TAFs), 33 of 95 (34%) were relatively unperfused at rest. Cell flux heterogeneity in TAFs decreased significantly by 27% from rest to hyperemia; the corresponding decrease (16%) in TAs was not significant. Thus, unperfused TAFs are present in a proportion which reflects capillary recruitment in hamster cremaster (Sarelius et al, Am J Physiol 1981;241:H317) while TAs are not, and TAFs independently modulate flow distribution distally while TAs do not. The data therefore support the conclusion that TAFs control cell flow in the distal microvasculature. Analysis of normalized ranked maximal diameters showed that TAFs unperfused at rest tend to be the smaller vessels at any tissue site. PMID- 2909295 TI - Comparative effects of hypoxia and ischemia in the isolated, blood-perfused dog heart: evaluation of left ventricular diastolic chamber distensibility and wall thickness. AB - To compare the effects of hypoxia and ischemia on left ventricular (LV) diastolic function, we studied 17 isolated, isovolumic dog hearts by measuring LV diastolic chamber distensibility (LV end diastolic pressure at constant volume), wall thickness, and myocardial pH in response to hypoxia at constant coronary flow or pressure versus global ischemia (zero coronary blood flow). Hypoxic perfusates consisted of methemoglobin-containing red blood cells suspended in lactated Ringer's solution. Brief cross-clamping of the coronary perfusion line was used to assess the contribution of coronary turgor to chamber distensibility and wall thickness. With hypoxia, left ventricles showed a significant early (5 minutes) decrease in diastolic distensibility and an increase in wall thickness, at either constant coronary perfusion pressure or flow. The increase in wall thickness was independent of hypoxia-induced changes in coronary turgor. In contrast, global ischemia produced an early increase in LV diastolic chamber distensibility and a decrease in wall thickness. When global ischemia was continued beyond 60 minutes, a decrease in LV chamber distensibility developed. This diastolic contracture was not associated with an increase in LV wall thickness. Myocardial pH decreased slightly during 15 minutes of hypoxia and markedly with 15 minutes of global ischemia. Thus, LV diastolic chamber distensibility decreased during 15 minutes of hypoxia, while an increase in distensibility was seen during global ischemia of similar duration. During hypoxia, these changes were associated with increased LV wall thickness, at either constant coronary perfusion pressure or constant coronary flow. Prolonged ischemia led to diastolic contracture without an increase in wall thickness.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2909296 TI - Lesion of the area postrema region attenuates hypertension in spontaneously hypertensive rats. AB - To determine whether the area postrema contributes to the development of hypertension in spontaneously hypertensive rats (SHR), sham or electrolytic lesions of the area postrema (AP) were made in 4-week-old SHR and Wistar-Kyoto (WKY) controls. From weeks 5 through 16, systolic pressure was measured via tail plethysmography. While blood pressure rose markedly in sham-operated SHR, increases in pressure were small in AP-ablated SHR and similar to those seen in all WKY. Subsequent direct measurements of mean arterial pressure in the same rats showed a significant correlation (r = 0.87, p less than 0.01) with the pressure data acquired via weekly tail-cuff measurement, thereby confirming that hypertension in AP-ablated SHR had indeed been attenuated. Analysis of several hundred computer-acquired measurements of mean arterial pressure from each rat showed that AP ablation shifted the distribution of mean arterial pressure to a lower range in SHR but not WKY. Ablation of the AP also decreased resting heart rate in SHR but not WKY. Suppression of heart rate in response to intravenous phenylephrine was equivalent in sham-operated and AP-ablated rats, suggesting that baroreflex-mediated slowing of heart rate was not impaired. In response to intravenous angiotensin II, suppression of heart rate was similar in sham and AP ablated SHR, and actually was enhanced in AP-ablated WKY. Histological evaluation of the lesions indicated that visible damage to the adjacent nuclei of the solitary tracts was confined to a small portion of the commissural nucleus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2909297 TI - Vascular responses to vasopressin are tone-dependent in the cerebral circulation of the newborn pig. AB - The effects of lysine vasopressin (LVP) on pial arteriolar diameter and cortical periarachnoid fluid prostanoid concentrations were investigated in newborn pigs. Chloralose-anesthetized piglets were equipped with closed cranial windows over the parietal cortex for observation of pial arterioles and collection of cerebrospinal fluid (CSF) passing over the cerebral surface. Prostanoids in the CSF were determined by radioimmunoassay. LVP (10-1,000 microU/ml) elicited concentration-dependent increases in pial arteriolar diameter associated with increased levels of 6-keto-prostaglandin (PG)F1 alpha, PGE2, thromboxane B2, and PGF2 alpha. LVP-induced pial arteriolar dilation was unchanged after intravenous indomethacin (5 mg/kg). Conversely, LVP constricts pial arterioles previously dilated by physiological (hemorrhagic hypotension) and pharmacological (topically applied PGE2 or isoproterenol) intervention. This constriction is potentiated by indomethacin. Vascular and biochemical changes elicited by LVP were blocked by intravenous [1-(beta-mercapto-beta beta-cyclopentamethylene propionic acid),2,(O methyl)-Tyr-AVP] (5 micrograms/kg), a putative V1 receptor antagonist, whereas vascular effects of norepinephrine and U46619, a thromboxane A2 mimic, were unchanged. Therefore, the degree of vascular tone appears to influence responses of the newborn pig cerebral circulation to LVP. PMID- 2909298 TI - Electrophysiological and anatomic differences between canine hearts with inducible ventricular tachycardia and fibrillation associated with chronic myocardial infarction. AB - This study examined electrophysiological and anatomic differences between dogs with ventricular tachycardia (VT) and fibrillation (VF) inducible by programmed ventricular stimulation 7-21 days after left anterior descending coronary artery ligation. Of 106 dogs studied, 40 had inducible VT, 19 had inducible VF, and 47 had no inducible arrhythmias. Differences between these three groups of animals were examined with cardiac mapping (to determine ventricular activation time in sinus rhythm) and post-mortem pathology (to measure infarct size and to reconstruct the anatomy at the infarct edge). Animals with inducible VT had longer maximal epicardial activation time (127 +/- 8 msec) than did animals with inducible VF (91 +/- 8 msec, p less than 0.05) or animals with no inducible arrhythmias (75 +/- 2 msec, p less than 0.001). Delayed epicardial activation occurred in 90% of animals with VT, 42% of animals with VF, and in only 6% of animals with no inducible arrhythmias. Endocardial and myocardial activation times were similar for the VT and VF groups. Infarct size was 18 +/- 2% of the ventricles for the VT group, much higher than for the VF group (11 +/- 2%, p less than 0.001) or for the group with no inducible arrhythmias (9 +/- 1%, p less than 0.001). The maximum diameter of viable muscle bundles interdigitating with scar tissue at the infarct edge was much larger in animals with VT (2.4 +/- 0.2 mm) than in animals with VF (1.8 +/- 0.2 mm, p less than 0.05) or animals with no inducible arrhythmias (1.7 +/- 0.1 mm, p less than 0.01). Thus, when compared with animals with inducible VF, animals with inducible VT had longer epicardial activation time, larger infarct size and viable muscle bundles of larger diameter at the infarct edge. PMID- 2909299 TI - Measurement of lung microvascular pressure in the intact anesthetized rabbit by the micropuncture technique. AB - We have developed a micropuncture technique for the measurement of microvascular pressure in the intact lung of rabbit. We anesthetized 16 rabbits (halothane, 0.8%) and mechanically ventilated them through a tracheotomy. Then, we exposed the right lung by rib resection over the right anterior chest. We measured pulmonary artery, left atrial, and systemic pressures by direct catheterization and cardiac output by the thermodilution technique. For micropuncture, we stabilized the lung on a shelf and stopped ventilation for 3-4 minutes at an airway pressure of 7 cm H2O. We injected pancuronium intravenously to paralyze the diaphragm and intercostal muscles. Of the total pulmonary vascular pressure drop, 52% occurred in the microvascular segment between arterioles and venules of 20 micron diameter, 28% occurred in the arterial segment, and 20% occurred in the venous segment. We conclude that in the intact lung of rabbit, the major pressure drop occurs in the microvascular segment. PMID- 2909300 TI - Differential accumulation of diacyl and plasmalogenic diglycerides during myocardial ischemia. AB - The recent discovery of neutral active choline and ethanolamine glycerophospholipid specific phospholipase C in myocardium (Wolf RA, Gross RW. J Biol Chem 1985;260:7295) has demonstrated a novel catabolic pathway that potentially contributes to the accumulation of amphiphilic metabolites during myocardial ischemia. To assess the potential importance of this pathway, we quantified the temporal course of alterations in myocardial 1-0-alk-1'-enyl-2 acyl-sn-glycerol (AAG) and 1,2-diacyl-sn-glycerol (DAG) content during control and ischemic intervals in an isolated perfused Langendorf model. AAG accumulated over fivefold to 8.70 and 18.27 nmol/g dry in 20- and 60-minute ischemic rabbit hearts, respectively (p less than 0.02). The only AAG molecular species that was detected in substantial amounts in control or ischemic rabbit hearts was 1-0 hexadec-1'-enyl-2-acyl-sn-glycerol. Since this molecular species is enriched in plasmenylcholine these findings suggest that AAG production is likely mediated by phospholipase C-catalyzed hydrolysis of plasmenylcholine. In contrast to ischemia induced AAG accumulation, DAG content decreased during both control and globally ischemic perfusion intervals. In summary, these findings demonstrate that AAG, in contrast to DAG, accumulates during myocardial ischemia indicating that at least some metabolites of plasmalogen and diacyl phospholipids accumulate at differential rates during myocardial ischemia. PMID- 2909301 TI - Patterns of endothelial microfilament distribution in the rabbit aorta in situ. AB - The available data on F-actin microfilament distribution in vascular endothelial cells in vivo is limited. In this study, the appearance and distribution of endothelial cell microfilaments in the rabbit thoracic aorta, the abdominal aorta and its major arterial branch points, and the aortic bifurcation were examined. Perfusion fixed rabbit aortas were stained in situ for F-actin by infusing rhodamine phalloidin via a peristaltic pump into the aortas at a slow flow rate. This new technique resulted in excellent visualization of branch points and allowed for a precise description of the actin microfilament bundles in endothelial cells along flow dividers. In the thoracic and abdominal aorta, away from branch ostia, actin microfilaments were localized in two regions of the endothelial cells, as a prominent band that completely outlined the cell periphery, and also as short central stress fibers. The central stress fibers were more frequent and prominent in cells of the abdominal aorta. At branch sites and at the aortic bifurcation, long, thick microfilament bundles were present in endothelial cells extending from the tip of the flow divider to a few millimeters along the branch arteries, the aorta, and the iliac arteries. Peripheral actin, however, no longer completely surrounded the cells. The thick bundles were not prominent in endothelial cells located adjacent to the proximal lip of branches or at the iliac arteries opposite the flow divider. This study shows that endothelial cell F-actin microfilament distribution in vivo is well defined along the aortic-arterial system. The prominent central microfilament bundles and the reduced peripheral microfilaments seen at localized regions may reflect an adaptive response to elevated shear stress at these sites. PMID- 2909302 TI - Cardiovascular effects of neuropeptide Y in rat brainstem nuclei. AB - Central catecholaminergic neurons are involved in cardiovascular regulation. Neuropeptide Y (NPY) coexists with adrenaline and noradrenaline in the rat brain, and interactions among these substances have been studied. The purpose of this study was to investigate the possible role of NPY in central cardiovascular control. Male Sprague-Dawley rats were anesthetized with urethane, and blood pressure was monitored intra-arterially. Intramedullary microinjection (60 nl) of NPY (0, 46.5 fmol, 465 fmol, 1.5 pmol, and 4.65 pmol) was made into the nucleus tractus solitarii (NTS), into the area postrema, and into the C1 area in the rostroventrolateral medulla. Injection site was identified by L-glutamate administration and confirmed histologically. Unilateral injection of NPY into the NTS produced a prominent dose-related decrease in heart rate and systolic and diastolic blood pressure (-106 +/- 8 beats/min, -56 +/- 2 mm Hg, and -33 +/- 2 mm Hg, respectively after 4.65 pmol NPY, n = 7, p less than 0.001). Maximal changes occurred at 30 seconds and recovered in 10 minutes for blood pressure and 20 minutes for heart rate. Injection into the area postrema produced an initial increase in heart rate and mean blood pressure (+23 +/- 2 beats/min and +18 +/- 2 mm Hg) followed by a prolonged decrease in heart rate and mean blood pressure ( 14 +/- 4 beats/min and -15 +/- 2 mm Hg, respectively, n = 7, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2909303 TI - Load responsiveness of protein synthesis in adult mammalian myocardium: role of cardiac deformation linked to sodium influx. AB - Exposure of adult mammalian myocardium to increased hemodynamic loads augments cardiac protein synthesis, ultimately leading to hypertrophy of the affected chamber. This established relationship between loading conditions and protein synthesis was examined in terms of two questions. First, is there a basic difference between the anabolic effect of a passive load imposed on diastolic myocardium and that of an active load generated by systolic myocardium? This issue was addressed by measuring [3H]phenylalanine incorporation into muscle protein in either quiescent or contracting ferret papillary muscles, set at known isometric lengths. Myocardial protein synthesis increased in proportion to total muscle tension in each case, with an equivalent relation describing both quiescent and contracting muscles. Synthesis of two contractile proteins, actin and myosin heavy chain, were enhanced by muscle loading. Thus, a quantitative rather than qualitative difference between the anabolic effects of diastolic and systolic loading was demonstrated. Second, since increased sodium influx is an initial cellular response requisite to the growth-inducing activity of many substances, and since sodium entry through stretch-activated ion channels is stimulated by deformation of the sarcolemma, does cardiac deformation during increased loading promote sodium influx as a signal to increase anabolic activity? In either quiescent or contracting papillary muscles, the rate of 24Na+ uptake was found to increase with load. Streptomycin, a cationic blocker of the mechanotransducer ion channels, was without effect on protein synthesis in stimulated but slack muscles; however, it inhibited, in a dose-related manner, the augmented protein synthesis otherwise observed in contracting muscles developing tension. At 500 microM, streptomycin did not reduce active tension, but it did reduce the synthesis of both actin and myosin heavy chain. In a second pharmacologic approach, inotropic agents were chosen which uniformly increased muscle tension development but which had contrasting effects on sodium influx. Protein synthesis increased in the presence of Na+ influx enhancers, monensin or veratridine; however, protein synthesis decreased in the presence of amiloride, a sodium influx inhibitor. Thus, myocardial protein synthesis varied directly with sodium influx despite the positive inotropic effect observed with each of these agents. In addition, inhibition of protein synthesis by ouabain demonstrated that activation of the Na+ pump is required for the anabolic effect of load.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2909304 TI - "Reperfusion injury" by oxygen-derived free radicals? Effect of superoxide dismutase plus catalase, given at the time of reperfusion, on myocardial infarct size, contractile function, coronary microvasculature, and regional myocardial blood flow. AB - Do oxygen-derived free radicals, generated at the time of reperfusion, lethally injure viable, previously ischemic myocardium, damage vascular endothelium, and impair recovery of postischemic contractile function? To address these issues, 23 anesthetized open-chest dogs underwent 2 hours of left anterior descending coronary artery occlusion followed by 4 hours of reperfusion. Immediately prior to reflow, each dog was randomized to receive either the free radical scavenging agents superoxide dismutase (SOD) + catalase, or saline alone. SOD + catalase had no significant beneficial effect on infarct size measured by triphenyltetrazolium staining: area of necrosis averaged 38.5 +/- 6.1% vs. 46.3 +/- 6.2% of the area at risk in treated compared with control animals respectively (p = NS). Furthermore, infusion of SOD + catalase did not alter contractile function of the viable subepicardium: mean segment shortening (measured using sonomicrometry) at 4 hours postreperfusion was -23 +/- 5% of baseline, preocclusion values in controls dogs and -24 +/- 9% of preocclusion values in animals that received the scavenging agents. However, SOD + catalase treatment preserved the endocardial microvasculature (assessed by semiquantitative electron microscopic analysis) and enhanced regional myocardial blood flow after reperfusion. Specifically, mean score for microvascular injury was 0.41 +/- 0.14 vs. 0.10 +/- 0.08 (p less than 0.05) in control compared with SOD + catalase treated groups, and blood flow averaged 0.56 +/- 0.11 vs. 1.27 +/- 0.33 ml/min/g tissue (p less than 0.05), respectively, in the previously ischemic endocardium at 2 hours postreflow. Thus, SOD + catalase given at the time of reperfusion had no acute beneficial effect on either the extent of myocyte necrosis or postischemic contractile function in this canine model. SOD + catalase did, however, attenuate both endocardial vascular injury and the "low reflow" phenomenon. These data suggest that microvascular injury and low reflow following prolonged (2 hour) but transient coronary occlusion may be mediated by oxygen-derived free radicals generated at the time of reperfusion. PMID- 2909305 TI - Oxygen consumption and coronary reactivity in postischemic myocardium. AB - Coronary vascular responses in regions of reversible postischemic myocardial contractile dysfunction (stunned myocardium) were examined in chronically instrumented, awake dogs. Left anterior descending coronary artery blood flow and oxygen extraction, aortic and left ventricular pressures, and regional myocardial segment shortening were determined. Regional myocardial blood flow was measured with microspheres. Coronary reactive hyperemia and vasodilator reserve, and regional myocardial oxygen consumption were determined. Three sequential 10 minute left anterior descending coronary artery occlusions separated by 30-minute reperfusion periods resulted in progressive postischemic dysfunction so that 1 hour after the final coronary artery occlusion, myocardial segment shortening was reduced to 37% of baseline. Despite this decrease in contractile function, left anterior descending artery flow (19.6 +/- 2.6 vs. 18.4 +/- 3.0 ml/min), myocardial blood flow and the transmural distribution of flow measured with microspheres, and regional myocardial oxygen consumption were unchanged. Although the coronary vasodilator reserve in response to adenosine was unaltered (63 +/- 9 vs. 70 +/- 15 ml/min), the reactive hyperemia response to a 10-second coronary occlusion was decreased in intensity (debt repayment ratio = 474 +/- 78% vs. 322 +/- 74%; p less than 0.05) and duration (57 +/- 9.1 vs. 35 +/- 4.5 seconds; p less than 0.05), while the peak flow response was unchanged (57 +/- 6.8 vs. 60 +/ 7.1 ml/min). Thus, in the intact awake animal postischemic myocardial contractile dysfunction was not associated with decreased myocardial oxygen consumption and did not impair the normal relation between coronary blood flow and myocardial oxygen utilization. Although coronary vessels showed a normal ability to vasodilate in response to adenosine, coronary reactive hyperemia was reduced. PMID- 2909307 TI - Report of the AFCR Public Policy Committee: current issues in public policy. PMID- 2909306 TI - AIDS policy--local realities and federal responsibilities. PMID- 2909308 TI - AIDS: issues in developing national policy. PMID- 2909309 TI - Risk of right bundle-branch block and complete heart block during pulmonary artery catheterization. AB - The need for the prophylactic insertion of a pacemaker before pulmonary artery catheterization in patients with pre-existing left bundle-branch block (LBBB) is controversial. To determine the incidence of new right bundle-branch block (RBBB) and complete heart block during bedside pulmonary artery catheterization, 293 patients undergoing 307 pulmonary artery catheterizations were prospectively studied. Nine patients had pacemaker rhythms and 19 patients had an RBBB on their precatheterization ECGs and therefore were excluded from analysis. In the remaining 279 pulmonary artery catheterizations, eight (3%) were associated with the development of a new RBBB. None of the 14 patients with a pre-existing LBBB developed complete heart block. The incidence of complete heart block during pulmonary artery catheterization of patients with previous LBBB was not higher than the incidence of RBBB in patients without underlying conduction defects. Because of the rare but grave consequences of RBBB in patients with pre-existing LBBB, we recommend the use of standby external pacemakers and equipment for transvenous pacemaker insertion in these patients during pulmonary artery catheterization. We do not recommend prophylactic pacemaker insertion. PMID- 2909310 TI - Just say no. PMID- 2909311 TI - Unusual case of metabolic acidosis. PMID- 2909312 TI - Fat embolism syndrome with no evidence of pulmonary involvement. PMID- 2909313 TI - Simple method for ventilating transported newborn infants. PMID- 2909314 TI - Catheter-related infections. PMID- 2909315 TI - Sequential physiologic interactions in pediatric cardiogenic and septic shock. AB - We report that the pediatric cardiogenic shock and septic shock populations show similar hemodynamic and oxygen utilization physiologic relationships during aggressive intensive care therapy. We examined the mathematical relationships between vascular tone and flow, and oxygen utilization and oxygen delivery (DO2) in the early and middle stages of cardiogenic and septic shock. The fitted curves between cardiac index and systemic vascular resistance, and oxygen consumption (VO2) and DO2 were clinically and statistically similar in both shock populations. We found no evidence for decreased oxygen extraction in sepsis as compared to the cardiogenic shock population. In addition, it appears that the major determinant of VO2 in these populations is DO2, not oxygen extraction. We suggest that patients with cardiogenic or septic shock can be treated according to similar physiologic principles. PMID- 2909316 TI - Validation of two scoring systems which assess the degree of physiologic instability in critically ill newborn infants. AB - Modifications of the Physiologic Stability Index (PSI) and Therapeutic Intervention Scoring System (TISS) were used to evaluate the physiologic stability and need for therapeutic intervention in 55 infants hospitalized in the newborn ICU. After modifying the PSI to reflect neonatal physiology, we found that PSI scores correlated significantly with TISS values (r = .75, p less than .001) and Nursing Utilization Management Intervention System (NUMIS) classifications (r = .62, p less than .001). TISS values also correlated with NUMIS scores (r = .72, p less than .001). PSI and TISS scores increased significantly with each increase in NUMIS classification (p less than .001 for all comparisons). PSI and TISS scores decreased significantly between admission and either discharge (n = 41) or day 14 of hospitalization (n = 14, p less than .001). PSI and TISS scores were greater on days 1 and 5 in infants with hyaline membrane disease when compared with infants with transient tachypnea (p less than .001). Infants with PSI scores greater than or equal to 4 and TISS scores greater than or equal to 7 on day 1 took significantly longer to achieve adequate protein calorie intakes than infants with lower first-day scores (p less than .002). The modified PSI and the TISS scoring systems are both useful objective measurements of the degree of physiologic instability in newborn infants requiring intensive care, and both scores identify those at increased risk for nutritional morbidity. PMID- 2909317 TI - Use of ranitidine in children undergoing cardiopulmonary bypass. AB - Sixty children aged 6 wk to 10 yr were studied. The children were undergoing cardiopulmonary bypass (CPB) for correction of congenital heart defects. The aim of the study was to provide prophylaxis for stress-induced gastric ulceration by elevating the gastric pH to at least 3.5. Two infusion regimes of ranitidine were compared: 0.1 and 0.2 mg/kg.h. The period of study was from induction of anesthesia until the end of the first 24 h after surgery. Both regimes were effective. The 0.2-mg/kg.h infusion produced a significantly higher plasma concentration of ranitidine throughout the study period without any additional clinical benefit. Both regimes produced, within 3 h of cessation of CPB, a significant elevation in mean gastric pH to at least 5.3. This paper concludes that 0.1-mg/kg.h infusion of ranitidine is a safe and efficacious regime for the critically ill pediatric patient. PMID- 2909318 TI - Blood histamine concentrations are not elevated in humans with septic shock. AB - Histamine has been suggested as an important mediator of the cardiovascular abnormalities during septic shock. To determine if blood histamine levels were increased during human sepsis and septic shock, plasma histamine was measured using a very sensitive radioenzyme assay employing histamine N-methyltransferase (HNMT) in the following patient groups: normal controls (n = 76), nonseptic critically ill (n = 12), nonseptic shock (n = 2), sepsis without shock (n = 28), and septic shock (n = 41). Using this enzyme binding assay, all these groups had similar, normal plasma histamine concentrations, except those patients with septic shock whose mean histamine measurements were significantly reduced (p less than .002). This decrease was found to be due to an artifact of the assay: plasma contained a circulating inhibitor that falsely lowered the measured histamine level. Fractionation of septic shock plasma using molecular exclusion membranes and gel filtration revealed a 5000 MW inhibitory factor. After removal of this inhibitor from plasma, septic shock plasma histamine levels were normal. Thus, septic shock patients may have a circulating inhibitor of the HNMT enzyme, but plasma histamine concentrations are normal. Histaminemia is unlikely to play an important role in the pathogenesis of septic shock in humans. PMID- 2909319 TI - Pentoxifylline improves survival following hemorrhagic shock. AB - Pentoxifylline is an agent which improves microcirculatory blood flow, but its use as therapy for shock has not been reported. We performed this study to determine if pentoxifylline improves survival following experimental hemorrhagic shock. Anesthetized Sprague-Dawley rats were studied; the animals were subjected to hemorrhage and then resuscitated using lactated Ringer's solution, with either placebo or pentoxifylline added by random selecting. Animals were then observed for 3 days. There was significantly increased survival in pentoxifylline-treated animals (p less than .05). In additional experiments, animals received more aggressive fluid resuscitation; improved survival in the pentoxifylline group was noted almost immediately and persisted through the 72-h period. This was significant at the p less than .01 level. We conclude that pentoxifylline improves survival from hemorrhagic shock in this experimental model, and has additive survival value to fluid resuscitation. PMID- 2909320 TI - Dimethyl-prostaglandin E2 prevents stress ulceration with minimal complications. AB - Gastric mucosal damage produced by topical application of necrotizing agents is diminished by topical or systemic pretreatment with a variety of E and F prostaglandins. The rat restraint model of gastric mucosal injury is more analogous to clinical stress ulceration than are models using intragastric application of toxic solutions; however, previous use of prostaglandin E1 in the restraint model resulted in a prohibitive incidence of GI morbidity. The current study used the restraint model of stress ulceration to compare the effects of a more potent prostaglandin analogue, 16,16-dimethyl prostaglandin E2, with hyperosmolar glucose and antacids. All three agents afforded significant protection from grossly apparent mucosal lesions, alone and in combination. Although other physiologic effects of each agent differed, the only effect which correlated with prevention of mucosal lesions was suppression of gastric acidity. Since effective doses of cytoprotective prostaglandins did not produce notable morbidity in comparison with other agents, they may prove to be a useful adjunct to stress ulcer prophylaxis in clinical settings. PMID- 2909321 TI - High-frequency oscillatory ventilation of a canine bronchopleural fistula. AB - We hypothesized that during high-frequency oscillatory ventilation (HFOV) of a central bronchopleural fistula (BPF), gas flow through the fistula (Vleak) should vary with ventilatory frequency. In six pentobarbital-anesthetized, open-chested dogs, we inserted a cannula into the left lower lobe bronchus. After 30 min of HFOV at 5 Hz (fistula closed), they received four periods of HFOV (fistula open) at frequencies of 5, 10, 15, and 20 Hz. With the fistula open, we could adequately ventilate at all four frequencies. Vleak ranged between 5.1 +/- 0.7 and 4.1 +/- 0.7 L/min and it was not significantly different at any frequency by analysis of variance. Airway opening pressure (Pao) was 3.9 +/- 0.6 cm H2O with the fistula closed. Pao decreased significantly to 1.9 +/- 0.2 cm H2O during 5 Hz ventilation (fistula open). Pao at the other frequencies was similar to fistula closed ventilation. We believe that expiratory flow limitation at frequencies greater than 5 Hz may explain our findings. PMID- 2909322 TI - Noninvasive assessment of cardiac output by impedance cardiography in the newborn canine. AB - Currently, critical care monitoring of cardiac function in the newborn human consists mainly of measuring heart rate and BP. A noninvasive technique for assessing cardiac output routinely in the critically ill neonate would facilitate clinical management. Impedance cardiography (IC) is a noninvasive technique which measures stroke volume on a beat-by-beat basis. This study compared cardiac output as measured by thermodilution (TD) to that measured by IC in seven canine pups 6 to 7 days old weighing 0.66 to 0.86 kg. Cardiac output was altered by the withdrawal and reinfusion of blood. There were no significant differences between the two methods for either the absolute value of cardiac output (r = .96) or the percent change in cardiac output (r = .97). Coefficients of variation were 3.0% for TD and 3.6% for IC. These results indicate that IC can be used to assess serially cardiac function in the newborn. PMID- 2909323 TI - Pulse oximetry during low cardiac output and hypothermia states immediately after open heart surgery. AB - Two commercially available pulse oximeters were found to read reliably early during periods of low cardiac index (CI) and low peripheral temperature (Tp). The lowest mean CI and mean Tp values at which a reading could be obtained were 2.4 L/min.m2 and 26.5 degrees C, respectively. The highest mean systemic vascular resistance index was 2930 dyne.sec/cm5.m2. The reliability of one monitor was equally good both in a normal and low perfusion mode (i.e., when the monitor displayed a low-quality signal message). The use of locally applied vasodilating creme widened the physiologic limits within which reliable measurements could be obtained. All oximeters and sensors overestimated slightly the saturation as compared to the hemoximeter readings, possibly because of a high mean carboxyhemoglobin concentration that was found to be present. PMID- 2909324 TI - Pressure-augmented fluid administration: modified system and general results. AB - Rapid fluid infusion is generally augmented by compression devices (pumps) that take advantage of compressibility of modern plastic fluid containers. The most commonly used pumps are not the most effective pressure sources for driving pressure. This paper describes the experience at a Level I trauma hospital with a relatively new device that serves as a more efficient source of pressure for rapid fluid administration. This device, commercially manufactured but locally modified, increases capability with minimal expense and additional training. PMID- 2909325 TI - Fellowship programs in critical care medicine: 1989/1990. Compiled and edited by the Society of Critical Care Medicine. PMID- 2909326 TI - Investigation on the protective value of breathing masks in farmer's lung using an inhalation provocation test. AB - Six subjects with farmer's lung underwent double inhalation challenge tests, each lasting 60 min, using natural antigen exposure. Subjects underwent the tests first without and then with protection by a particle-filtering half mask. Our purpose was to determine whether and to what extent the use of such masks reduced or prevented symptoms in affected patients. Clinical assessment included general and pulmonary symptoms, HR, temperature, WBC count, R, ITGV, VC, TLC, PO2, DCO, and chest x-ray film. The unprotected challenge provoked late responses characteristic of extrinsic allergic alveolitis. In the challenge using the mask, all six patients reported to be completely free of symptoms. Compared with the test without a mask, a statistically significant reduction in the rise of temperature, WBCs, HR, R, TLC, and PO2 was observed. Compared with the initial values, a statistically significant reduced increase of temperature and leukocytes was demonstrated in the test using the mask. Pulmonary and systemic alterations were significantly reduced but not completely prevented by the application of the particle-filtering half mask. PMID- 2909327 TI - Effect of menses, estrogens and hemolysis on a serum-lectin-like factor in cystic fibrosis. AB - Twelve CF heterozygous and two CF homozygous women who were tested serially for the CF-lectin activities during one to two months of their menstrual cycles, were found consistently to have negative tests during menses. The specific hormonal alteration during menses that affects the assay is unknown. However, estrogenic medication administered without progesterone to postmenopausal heterozygous women also caused false-negative tests, suggesting that a balance between progesterone and estrogen is critical for the CF-lectin activity; mere depletion of these hormones alone does not interfere. The addition of estrogen in vitro also inhibited the CF-lectin activity at a physiologic concentration of 10(-6) M, and addition of an equivalent concentration of progesterone blocked this inhibitory effect. Future studies of the CF-lectin or its assay as a potential CF-carrier test must be limited to those women not menstruating at the time of blood drawing and not receiving estrogens. Hemolysis or contamination of the serum with RBC should invalidate that sample for testing, although the effect of RBC contamination can be circumvented with the addition of mannose. A more objective, simplified means of performing the CF-lectin assay is reported. A preliminary blind study taking these issues into consideration was 100 percent correct in detecting 16 CF patients and 17 obligate heterozygotes, and revealed 4 percent of 64 control subjects to have positive tests. The presence of this lectin-like factor may reflect the underlying biochemical defect responsible for this disease. PMID- 2909328 TI - Differences in plethysmographic lung volumes. Effects of linked vs unlinked spirometry. AB - Determination of absolute lung volumes in patients is most reliable when measured with body plethysmography. Many laboratories use data obtained with a spirometer not directly linked to the plethysmograph to calculate total lung capacity (TLC) and residual volume (RV) from thoracic gas volume (Vtg) measured at functional residual capacity (FRC) in the plethysmograph. The reliability of these calculations depends on the stability of FRC between these separate devices. We examined the differences in TLC and RV values calculated with linked and unlinked spirometers in 220 patients and found them statistically significant (p less than 0.05). Additionally, differences exceeding the 95 percent confidence intervals for repeated, linked determinations occurred in more than 5 percent of patients. The large-volume differences in TLC were often associated with differences in expiratory reserve volume (ERV) in the opposite direction, suggesting a shift in FRC. However, clinical diagnoses were infrequently (4/220) altered by these differences, and recognition of the shift in FRC should further reduce this error. Therefore, the unlinked method appears acceptable. PMID- 2909329 TI - Exercise testing in women with chest pain. Are there additional exercise characteristics that predict true positive test results? AB - Women have a notoriously high rate of false positive exercise test results. Since the exercise ST segment response has low specificity in predicting CAD in women, we examined additional exercise parameters in 200 women with a history of chest pain compatible with angina and having ST segment depression greater than or equal to 1 mm recorded during a Bruce treadmill test. All subsequently had coronary arteriography. Two groups were compared: group A (n = 80) with CAD (greater than or equal to 70 percent stenosis of one or more coronary artery) and group B (n = 120) with angiographically confirmed normal coronary arteries (normal or minimal placquing). The exercise criteria analyzed included: (1) chest pain during exercise, (2) percent target heart rate, (3) extent of ST shift, (4) morphology of the ST segment slope, (5) time to normalization of the ST segment, and (6) total exercise duration. Multivariate analysis (using a stepwise logistic regression model) identified four independent exercise variables associated with the likelihood of CAD: (absence of MVP, p = .003; exercise duration less than 5 min, p = .02; ability to reach target heart rate, p = .027; time to ST normalization greater than or equal to 6 min, p less than .001). False positive exercise test results were more likely to occur when the following exercise test variables were present: ability to exercise to stage 3 of the Bruce protocol and a rapid (less than or equal to 4 minutes) normalization of ST shift after cessation of exercise. Attention to these additional exercise variables allows more careful selection of women requiring more definitive (and expensive) testing. PMID- 2909330 TI - Pott's disease. A resurgent challenge to the thoracic surgeon. AB - Nineteen patients were treated at the Los Angeles County Harbor/UCLA Medical Center between 1971 and 1986 for tuberculosis of the spine. Fourteen were immigrants, a high-risk group. A high index of suspicion is required for Pott's disease, which occurs in fewer than 1 percent of patients with tuberculosis, often presents with nonspecific symptoms, and may result in permanent deformity or neurologic impairment. CT scan, the most useful diagnostic test, showed abnormal results in 11 of 11 patients. MRI, a newer modality, may provide even more information. Eight patients required operation in addition to antimicrobial therapy. Four had lesions between T3 and T10, where the spinal canal is narrow, of whom three (75 percent had neurologic involvement. All four underwent anterior approach (thoracotomy) for decompression, debridement, and spinal fusion. Fifteen had lesions between T11 and S2. Three (20 percent) had neurologic involvement but responded to medical treatment alone. Four underwent drainage of abscess or spinal fusion for deformity. Combined surgical and medical treatment gave excellent results in this series. PMID- 2909331 TI - Multicentricity of adenocarcinoma of the lung. AB - In a consecutive series of 62 lung resections for bronchogenic adenocarcinoma, 12 patients (19 percent) were found to have two or more adenocarcinomas on careful pathologic examination. These tumors all met the criteria for separate primary malignancy. In only two of the patients were the additional lesions suspected preoperatively. This incidence of multiple primary lung adenocarcinomas in apparently operable patients is several fold higher than would be anticipated from the literature. The phenomenon has important implications for preoperative radiologic evaluation, postoperative pathologic examination, assignment of TNM stage, and clinical follow-up of patients undergoing successful resection. PMID- 2909332 TI - Patterns and routes of tracheobronchial colonization in mechanically ventilated patients. The role of nutritional status in colonization of the lower airway by Pseudomonas species. AB - Tracheobronchial colonization by Gram-negative bacteria is common in mechanically ventilated patients. Pseudomonas sp are commonly isolated from the lower airways. We hypothesized that Pseudomonas sp would preferentially colonize the lower airway and would be more common in patients with poor nutritional status. We serially collected 75 pairs of upper and lower respiratory tract cultures from 14 patients treated with mechanical ventilation for at least one week, examined patterns of airway colonization and routes of bacterial entry for Pseudomonas sp and other enteric Gram-negative bacteria (EGNB), and related these findings to host-associated factors, including nutritional status. Pseudomonas sp were the most common species isolates taken from the lower airway, found in nine of 14 patients and in 41.3 percent of all cultures. In contrast to other EGNB, Pseudomonas sp were found significantly (p less than or equal to 0.05) more often in the tracheobronchial tree (31 of 75 cultures) than in the oropharynx (18 of 75 cultures). Primary colonization of the lower airway by Pseudomonas sp was found in four patients, while other EGNB never followed this pattern when subjects were studied with cultures taken every third day. A host-related factor related to lower airway colonization by Pseudomonas species was poor nutritional status, assessed by a multifactorial index (p less than or equal to 0.01). We conclude that in mechanically ventilated patients, Pseudomonas sp colonize the lower airway in a different pattern and by a different route from those of other EGNB. The findings that Pseudomonas sp preferentially colonize the tracheobronchial tree may be important for the design of strategies to prevent airway colonization. The recognition that poor nutritional status, a potentially modifiable host-related factor, favors lower airway growth of Pseudomonas sp suggests one direction for future infection-control efforts. PMID- 2909333 TI - Unsuspected hemodynamic alterations during endotracheal suctioning. AB - Endotracheal suctioning of intubated patients is associated with hemodynamic complications including arterial hypoxemia, cardiac arrhythmias, hypotension and even death. Prior investigations of this subject focus primarily on arterial hypoxemia. Our observations of ETS revealed significant falls in the mixed SvO2 and we postulated that alterations in VO2 or CO must be occurring. This study was then designed to determine the alterations in CO, VO2, SaO2 and the resulting effect on SvO2 during ETS. Ten critically ill intubated patients with pulmonary artery catheters in place, were studied during routine ETS by the nursing staff. We found that ETS produced a significant decrease in SvO2 which was predominantly due to an increased VO2 accompanied by an inadequate rise or even fall in CO. Alterations in SaO2 appeared to be modest and were insensitive indicators of alterations in SvO2. PMID- 2909334 TI - Rapidly progressive pneumonia in a patient with chronic obstructive pulmonary disease. PMID- 2909335 TI - Pulmonary function in long-term survivors of thoracoplasty. AB - Pulmonary function was assessed in 15 patients who had undergone thoracoplasty (TPL) approximately 30 years previously. Relation was noted to extent of TPL performed, side of TPL, age at TPL, and degree of secondary scoliosis. Test results showed mixed restrictive and obstructive defects. Although extent of TPL did not correlate with current lung function values, the restrictive defect was probably caused by a mixture of (a) compression of lung by TPL and (b) fibrosis from old pulmonary tuberculosis. The obstructive defect might have been due to the TPL procedure itself or to chronic bronchitis related to (a) previous pulmonary TB or (b) cigarette smoking, since 14 subjects were former or current smokers. That Dsb was relatively preserved suggests that pulmonary hypertension as a late sequela of TPL may be reactive (secondary to hypoxemia and respiratory acidemia) rather than obliterative. PMID- 2909336 TI - Respiratory diseases from hard metal or cobalt exposure. Solving the enigma. PMID- 2909337 TI - Expiratory mechanics before and after uncomplicated heart surgery. AB - In 12 mechanically ventilated anesthetized paralyzed patients undergoing cardiac surgery for either coronary bypass or for correcting valvular dysfunction volume, airflow, tracheal, esophageal, and transpulmonary pressures were measured. Respiratory system elastance and resistance were partitioned into their lung and chest wall components throughout tidal relaxed expiration. Measurements were performed prior to thoracotomy and just after rib cage closure. Before surgery, patients with valvular disease had significantly higher respiratory system and lung elastances and resistances than those with ischemic heart disease. After surgery, patients with valvular disease showed a decrease in respiratory system and lung resistances. Surgery strikingly modified chest wall resistive properties in both groups. Postoperatively, the mechanical properties of the respiratory system were very similar in valvular and ischemic patients. PMID- 2909338 TI - The safety factor for electroventilation measured by production of cardiac ectopy in the anesthetized dog. AB - The safety factor of electroventilation (ie, the ratio of the current required to produce an ectopic beat to the current required to produce an inspired volume of 225 ml, which is approximately twice tidal volume) was determined in 12 pentobarbital-anesthetized dogs using transthoracic electrodes positioned at the optimal electroventilation site. The optimal stimulation site for electroventilation was first determined using hand-held, stimulating electrodes. Then electrodes, 4.1 cm in diameter, were sutured bilaterally to the optimal stimulation site. The relationship between inspired volume and stimulus intensity was determined using a 0.8-s burst of stimuli (60/s) with a pulse duration of 0.1 ms. Using the same electrodes, the threshold current for producing ectopic beats was determined for single pulses ranging from 0.1 to 10 ms duration. In all dogs, the current required to produce an ectopic beat increased greatly as the pulse duration decreased. At 0.1 ms, the safety factor for electroventilation was calculated to be 25.8. PMID- 2909339 TI - Bronchoalveolar lavage plasmacytosis in a patient with a plasma cell dyscrasia. AB - A patient with serum monoclonal gammopathy, Bence-Jones proteinuria, and bone marrow plasmacytosis underwent fiberoptic bronchoscopic study for evaluation of interstitial lung disease. Bronchoalveolar lavage fluid contained 47 percent plasma cells, which were monoclonal by immunoperoxidase staining. This is the first time BAL plasmacytosis has been demonstrated in a patient with a plasma cell dyscrasia. PMID- 2909340 TI - Pulmonary artery thrombus detection by magnetic resonance imaging. AB - We report a patient in whom cardiac magnetic resonance imaging detected a clinically unsuspected pulmonary artery thromboembolus. Follow-up MRI after surgical removal of the thromboembolus showed normal pulmonary arteries. This case illustrates the potential utility of MRI in the detection and follow-up of central pulmonary artery thromboembolism. PMID- 2909341 TI - Severe pulmonary hypertension with diffuse smooth muscle proliferation of the lungs. Pulmonary tuberous sclerosis? AB - A 49-year-old man with normal intelligence and no cutaneous lesions had symptoms and signs of cor pulmonale. The chest roentgenogram showed an interstitial pattern. Hemodynamic studies revealed increased pulmonary arterial and wedge pressures. The patient died in shock, and the postmortem findings were a diffuse smooth muscle proliferation in the lungs as the cause of the pulmonary hypertension. We presume that this is a form of pulmonary tuberous sclerosis of which few cases are reported with such severe pulmonary hypertension as shown by our measurements. PMID- 2909342 TI - Pulmonary nodule mimicked by ECG lead artifact. AB - Recently, a new ECG lead has been introduced that can mimic a pulmonary nodule to the uninitiated. Alternatively, in those institutions where the lead is commonly seen, physicians may dismiss a real finding on the chest x-ray film as a lead "artifact." We describe the appearance of this new chest wall artifact. PMID- 2909343 TI - Pulmonary zygomycosis. A cause of positive lung scan diagnosed by bronchoalveolar lavage. AB - The diagnosis of pulmonary zygomycosis usually depends on the detection of fungal hyphae in biopsied tissue specimens. We describe a patient with a high probability lung scan and diffuse pulmonary infiltrates due to Zygomycetes diagnosed by the demonstration of nonseptate hyphae in bronchoalveolar lavage fluid. PMID- 2909344 TI - Late dissemination of pulmonary blastomycosis during ketoconazole therapy. AB - We report a patient with pulmonary blastomycosis who suffered relapse with dissemination of her disease after five months of apparent response to therapy with ketoconazole, 400 mg daily. Common causes of drug failure, including noncompliance and failure of absorption, were excluded, and there was no evidence of altered host immunity. Previous reports of relapse during and after ketoconazole therapy are reviewed; no previous case was found with recurrence near the end of a six-month period of apparently effective therapy. Close followup during the entire course of ketoconazole therapy for blastomycosis and following its completion is recommended. PMID- 2909345 TI - Unusual rib destruction in pleuropulmonary tuberculosis. AB - Two cases of pleuropulmonary tuberculosis had local rib destruction simulating malignancy. There was no superficial abscess formation which was the usual clinical feature of rib tuberculosis. Computerized tomography was valuable in demonstrating and assessing the extent of skeletal involvement. PMID- 2909346 TI - Bilateral rupture of diaphragm with delayed strangulation. AB - A 64-year-old woman presented in shock. The computed tomography (CT) scan confirmed rupture of the left diaphragm with strangulation. Three days after surgery, the patient developed herniation of abdominal contents on the right side with cardiorespiratory collapse. Marlex mesh was used to repair on the right side. Postoperatively, she needed partial gastrectomy for massive duodenal ulcer bleeding. A dual chamber pacemaker was used to correct the complete heart block. PMID- 2909347 TI - Solitary bronchial mucosal neuroma. AB - A 68-year-old man who had had cough and sputum for ten months was referred to our hospital because sputum cytologic findings were suggestive of lung cancer. Fiberoptic bronchoscopy and biopsy revealed mucosal neuroma of the bronchi. There were no signs suggesting pheochromocytoma or medullary thyroid carcinoma. To our knowledge, this is the first case of solitary mucosal neuroma of the bronchi to be reported. PMID- 2909348 TI - Sudden death and pacemakers. PMID- 2909349 TI - Clinical predictors of malignancy. PMID- 2909350 TI - Perfusion scan defects. PMID- 2909351 TI - Adverse effects of amiodarone at low doses. PMID- 2909352 TI - Cigarettes and caffeine. PMID- 2909353 TI - Occupational asthma from cobalt sensitivity in workers exposed to hard metal dust. AB - Eight asthmatic patients who had no history of asthma before starting work in a hard-metal plant and eight control subjects (three atopic, three nonatopic asthmatic, and two normal volunteers) without a history of exposure to hard metal dust were subjected to provocation tests, skin tests, radioallergosorbent tests (RAST) and Farr test with cobalt. Four of the eight patients were atopic, and seven showed bronchial hyperresponsiveness to methacholine (BHR). Patch and intradermal skin tests with cobalt chloride (CoCl2) could not discriminate the patients from control subjects. All patients had positive reactions to CoCl2 in the provocation tests; two developed immediate asthmatic reaction (IAR), four late asthmatic reaction (LAR), and two dual asthmatic reaction (DAR), while the control subjects showed no reaction. Evidence of specific IgE antibodies to cobalt-conjugated human serum albumin (Co-HSA) was presented by four patients (RAST score greater than 2) based on comparison of serum samples from 60 asthmatic patients and 25 asymptomatic workers in the same plant. Positive serum samples selectively bound 57Co, and the test was blocked by nonlabled cobalt sulfate (CoSO4). These findings suggest the development of hard metal-induced asthma from cobalt sensitivity. PMID- 2909354 TI - Bronchoalveolar lavage lipids in idiopathic pulmonary fibrosis. PMID- 2909355 TI - Factors determining in-hospital or late survival after aortic valve replacement. AB - To ascertain incremental risk factors for in-hospital and late mortality of patients undergoing AVR with the bovine pericardial valve, multiple variables were analyzed in a group of 240 patients undergoing AVR between 1977 and 1983. Follow-up totaled 12,023 patient-months (mean, 52.7 +/- 1.7 patient-months) and was 100 percent complete. Univariate analysis of incremental risk factors for in hospital mortality identified the following: age over 60 years (p = 0.015); and advanced preoperative NYHA class (p = 0.003). Multivariate analysis of risk factors for in-hospital mortality identified the following: age (p = 0.038); NYHA class (p = 0.018); and year of operation (p = 0.049). Incremental risk factors for late mortality were identified as age (p = 0.003), year of operation (p = 0.003), concomitant procedure (p = 0.047), and valvular lesion (regurgitation) (p = 0.053). Actuarial survival of patients (+/- SE) was 87 +/- 2 percent, 75 +/- 3 percent, and 61 +/- 5 percent at 2, 5, and 8.7 years, respectively. The actuarial survival of patients experiencing valve-related events was 62.6 +/- 10.1 percent at 8.7 years, compared to 55.4 +/- 7 percent for those who did not (p = 0.38). PMID- 2909356 TI - Hypermagnesemia. A potential complication during treatment of theophylline intoxication with oral activated charcoal and magnesium-containing cathartics. AB - Toxic reaction to theophylline compounds is common. Oral activated charcoal (OAC) is a widely accepted mode of therapy for management of moderate to severe cases of theophylline toxicity. Magnesium-containing cathartics are generally recommended in conjunction with OAC in the treatment of drug or toxin ingestions. We report two cases of hypermagnesemia complicating the treatment of theophylline toxicity with OAC and magnesium citrate. In both patients, the hypermagnesemia contributed significantly to morbidity or mortality. In light of these cases and after review of the literature, we suggest that sorbitol be considered the cathartic agent of choice in the treatment of theophylline toxicity with OAC. PMID- 2909357 TI - Sleep quality and pulmonary function in the healthy elderly. AB - Loss of sleep causes deterioration of pulmonary function and ventilatory responsiveness in normal humans and in patients with chronic obstructive pulmonary disease. To evaluate the effects of variations in sleep quality on breathing, we studied 48 healthy elderly volunteers (mean age, 70 years). Electroencephalographically derived indices of sleep quality were correlated with spirometric performance, MIP, MEP, and waking SaO2. We found significant correlations between several indices of sleep quality and the spirometric measurements in the group as a whole, and striking correlations between sleep quality and PFTs in those with sleep efficiency less than or equal to 70 percent. We conclude that sleep disturbance may be related to poor performance on PFTs. These results suggest that spirometry should be performed on well-rested patients. The results also point to sleep quality as a potentially important variable in the management of patients with pulmonary disease. PMID- 2909358 TI - Thrombosis: the major Hickman catheter complication in patients with solid tumor. AB - Major complications of Hickman catheter placement (thrombosis and infection) were determined in 168 patients with solid tumor (lung, 79; head and neck, 56; esophagus, 24; and miscellaneous, 9). Catheter-related thrombosis was clinically detected in 22 individuals and was detected at autopsy in six (total 17 percent). The 17 percent figure underestimates the true incidence of thrombosis since only 25 percent of study patients had autopsies. Patients with adenocarcinoma of the lung constituted a high risk group. Nine of 20 (45 percent) of these patients had thrombosis compared to 25, 9, and 16 percent of patients with squamous cell cancers of lung, head and neck and esophagus, respectively (p less than 0.002). Three patients with thrombosis had pulmonary emboli and two died. Thrombosis occurred despite daily heparin catheter flushing. INfections occurred in 11 patients. One had suspected endocarditis, one had a subcutaneous tunnel infection, and nine had exit site infections. All responded to local or systemic antibiotics. Better methods to prevent thrombosis are needed. PMID- 2909359 TI - Changes in phosphatidylglycerol in bronchoalveolar lavage fluids from patients with cryptogenic fibrosing alveolitis. AB - In view of recent evidence that changes in phospholipid components of pulmonary surfactant occur in bleomycin-induced pulmonary fibrosis, the aim of this study was to examine whether similar changes occur in patients with idiopathic pulmonary fibrosis. We have analyzed phospholipid profiles in bronchoalveolar lavage (BAL) fluids from a group of 32 patients with "lone" cryptogenic fibrosing alveolitis (CFA) compared with 17 control subjects. Prior to treatment, resembling the findings in bleomycin fibrosis, many CFA patients had decreased proportions of phosphatidylglycerol (PG) (percent of total phospholipid; median 10.5, range 0 to 35.1 compared with 18.2, range 9.6 to 24.2 for the control group of similar age range and smoking habits; p less than 0.01). Following the initial lavage, the patients were treated with prednisolone. The initial percentage of PG levels did not predict response to prednisolone, but serial lavage studies conducted in 14 patients suggest that an early and sustained increase in percentage of PG following commencement of prednisolone is associated with clinical improvement. The reasons for the proportional reductions in phosphatidylglycerol, and whether they result in functional deficiency of surfactant in CFA, need to be explored. PMID- 2909360 TI - Respiratory muscle performance in normal elderly subjects and patients with COPD. AB - We studied the reproducibility of tests of RM performance in normal elderly subjects and compared their performance with that of patients with COPD. The RM strength was measured as MIP and MEP. The RM endurance was measured using a two minute incremental threshold loading test. The max load, the average Ppk as %MIP at max load and the Pmean at max load were taken as measures of respiratory muscle endurance. The MIP, but not MEP, was less in COPD patients than in normal subjects (p less than 0.05). There was a small increase in between visits, in MIP in the normal subjects. All measures of RM endurance were much lower in the COPD group than in the normal elderly (p less than 0.05). We conclude that (1) RM strength and endurance are reproducible in normal elderly subjects and patients with COPD, (2) that COPD subjects have decreased RM strength and endurance compared with normal elderly subjects, and (3) that in COPD subjects RM endurance is compromised more than RM strength. PMID- 2909361 TI - Negative pressure ventilation. Effects on ventilation during sleep in normal subjects. AB - Negative pressure ventilation (NPV) is used for ventilatory support of patients with respiratory failure due to neuromuscular disorders and thoracic deformities, and to provide ventilatory muscle rest for patients with severe chronic airflow limitation. To determine whether NPV would result in episodes of upper airway obstruction during sleep, we studied five normal subjects on two consecutive nights with the first night serving as a control and NPV being administered on the second night. Ventilators were adjusted so as to reduce the peak phasic diaphragm electromyogram signal by at least 50 percent. All subjects demonstrated an increase in the total number of apneas + hypopneas per hour on NPV control nights. Although differences were not significant, there was a tendency to develop decreased sleep efficiency, sleep fragmentation and altered sleep architecture with NPV. We conclude that nocturnal NPV can induce sleep apneas and impair sleep quality in normal subjects. PMID- 2909362 TI - A sex-specific endogenous stimulatory rhythm regulating prolactin secretion. AB - In the rat, PRL secretion is under inhibitory control by tuberoinfundibular dopaminergic neurons. The levels of dopamine (DA) in hypophysial portal blood decline during surges of PRL secretion (e.g. suckling and cervical stimulation). However, this decline alone is not sufficient to account for the amount of PRL released. In this study we investigated the possible existence of an endogenous stimulatory rhythm for PRL secretion that may be masked by the tonic inhibitory tone of DA and unmasked by the DA-lowering effects of cervical stimulation. The PRL secretory response to pharmacological depression of DA-ergic tone was studied in ovariectomized (OVX) female, adult castrated (AC) male, neonatally androgen sterilized (TP) female, and neonatally castrated (NC) male rats. Since mated rats have serum PRL surges at 0300 and 1700 h, these groups were treated with 200 micrograms/kg domperidone (DOM), iv, at 0300 h, 1700 h, or the intersurge interval, 1200 h. Serial blood samples were collected immediately before and at frequent intervals after DOM injection. OVX female rats had significantly greater serum PRL responses to DOM at 0300 and 1700 h than at 1200 h. AC male rats secreted significantly less PRL in response to DOM compared to OVX rats, and their PRL responses to DOM were similar at all three times. TP female rats had PRL secretory responses similar to those of the OVX rats at 1200 h, and the responses at 0300 and 1700 h were similar. NC male rats had PRL secretory responses similar to those of AC male rats. There was no difference between the PRL secretory profiles at any time after DOM injection in NC rats. These data provide evidence for an endogenous stimulatory rhythm for PRL secretion that is specific to female rats. They further suggest that the neonatal steroid environment is critical for differentiation of some sexually specific characteristics. PMID- 2909363 TI - Stimulation of testosterone production in the cynomolgus monkey in vivo by deglycosylated and desialylated human choriogonadotropin. AB - Modifications of carbohydrate structures of hCG, such as deglycosylation or desialylation, have been shown to reduce the biological activity of the hormone derivatives in vivo. We posed the question of whether deglycosylated hCG (dg-hCG) and desialylated hCG (ds-hCG) would behave as agonists at the LH/CG receptor in the primate in vivo, as this would bear on their potential clinical utility as LH/CG agonists or antagonists. Thus, we administered large doses (approximately 3 nmol) of highly purified dg-hCG, ds-hCG, hCG, or normal saline as a rapid iv injection to adult male cynomolgus monkeys (n = 3/group). Mean areas under the curves of plasma T over the first 6 h achieved with dg-hCG and ds-hCG were about 5-fold, significantly (P less than 0.05) greater than that in the saline controls and not significantly (P greater than 0.05) different from that in hCG-injected animals. Despite comparable plasma T responses in the first 6 h, mean plasma concentrations of ds-hCG, dg-hCG, and hCG differed dramatically among the groups. Plasma ds-hCG and dg-hCG levels were undetectable by 15 and 180 min, respectively, while the mean plasma hCG level was more than 2.10 nmol/L at 360 min. These data indicate that 1) dg-hCG is a full agonist at the LH/CG receptor in the primate in vivo, despite having minimal intrinsic activity in the rat Leydig cell adenyl cyclase assay and being able to near-completely antagonize hCG action therein; and 2) ds-hCG is a full agonist in the monkey in vivo, capable of stimulating a full testicular response over 6 h, despite being cleared from the circulation in 15 min. We conclude that the signal transduction system at the monkey LH/CG receptor is capable of achieving full steroidogenesis despite dramatically shortened exposure to stimulus or exposure to a stimulus with markedly reduced adenyl cyclase-stimulating activity in vitro. PMID- 2909364 TI - Lactation elevates vasoactive intestinal peptide messenger ribonucleic acid in rat suprachiasmatic nucleus. AB - Vasoactive intestinal peptide (VIP) has been suggested to play a role in lactation; indeed several studies implied that VIP induces the release of PRL in the pituitary. Quantitative RNA studies from our laboratory show an increase in the VIP messenger RNA (mRNA) content in the hypothalamus of lactating rats. The purpose of this investigation is to determine which hypothalamic neurons are increasing the expression of VIP. A sensitive in situ hybridization assay employing synthetic oligodeoxynucleotide probes corresponding to specific exons of the VIP gene was used to study VIP gene expression at the neuronal level. We were able to detect VIP-encoding transcripts in various brain regions including the ventrolateral thalamus, neocortex, pyriform cortex, and hypothalamus with a particularly high concentration in the suprachiasmatic nucleus. When lactating animals were compared to non-lactating animals, a 2-fold increase was observed in VIP transcripts in the suprachiasmatic nucleus. Since the suprachiasmatic nucleus is not directly associated with the physiology of lactation, the response of the VIP gene to lactation may be, in part, indirect. Taken together, our results suggest that lactation and the expression of the VIP gene are interrelated. PMID- 2909365 TI - A novel hepatic nucleotide is correlated with the carbohydrate induction of messenger ribonucleic acid-S14. AB - To determine whether the rapid response of hepatic mRNA-S14 to carbohydrate feeding was associated with an alteration in a specific hepatic nucleotide, acid extracts of liver tissue were analyzed by ion-paired reverse phase HPLC. A nucleotide present in nanomoles per g quantity correlated with the induction of this mRNA by sucrose. Four hours after sucrose feeding the content of this compound was 7 times greater than that in fasted rats. Furthermore, the response was rapid, attaining maximal levels 30 min after feeding, and remaining elevated for at least 4 h. The content of this nucleotide also correlated with the content of mRNA-S14 in the steady state, with the lowest levels of both mRNA-S14 and this nucleotide in fasted rats, intermediate levels in rats maintained on a regular chow diet, and the highest levels in rats fed a 60% sucrose diet for 4 days. Lastly, while the response of mRNA-S14 to thyroid hormone and sucrose is synergistic, the thyroidal state does not influence the response of this compound to sucrose. Thus, the interaction of thyroid hormone and sucrose on mRNA-S14 is distal to the generation of this compound. Based on the UV spectrum, HPLC retention, and [3H]adenosine labeling, this compound contains adenine. However, it is not any of the common adenine-containing mono- or oligonucleotides. These data indicate that a novel hepatic nucleotide is induced by sucrose and raise the possibility that this nucleotide is responsible for the induction of carbohydrate responsive mRNAs. PMID- 2909366 TI - Hybridization in situ studies of angiotensinogen gene expression in rat adrenal and lung. AB - Both rat adrenal and lung contain low levels of angiotensinogen mRNA, as shown by Northern blot and nuclease S1 analyses of RNA extracted from these tissues. We sought to identify the cellular localization of angiotensinogen mRNA in these two tissues using hybridization in situ of tissues obtained from both control rats and rats administered a combination of dexamethasone, ethynylestradiol, and T3. For the adrenal of hormone-treated rats, angiotensinogen mRNA was identified in periadrenal fibroblast-like cells and brown adipose tissue. For control rats, positive hybridization was obtained for fibroblast-like cells immediately adjacent to the adrenal capsule, but not for periadrenal brown adipose tissue. No hybridization was obtained for cells of the adrenal cortex, medulla, capsule or vessels. For the lung of hormone treated, but not control rats, angiotensinogen mRNA was identified in perivascular and peribronchial fibroblast-like cells and brown adipose tissue in the lung hilum. No hybridization was obtained for pulmonary parenchyma, bronchi, or vessels. These results confirm the widespread tissue distribution of angiotensinogen mRNA, and provide further evidence for the formation of angiotensin within tissues by mechanisms independent of the circulating renin-angiotensin system. PMID- 2909367 TI - Estrogen regulation of prolactin gene transcription in vivo: paradoxical effects of 17 beta-estradiol dose. AB - We investigated in male rats the effects of a range of doses of 17 beta-estradiol on PRL gene transcription, the level of circulating estradiol, and the levels of nuclear and cytosolic forms of the anterior pituitary estrogen receptor. One hour after 17 beta-estradiol injection, transcription of the PRL gene was significantly stimulated by 0.1 micrograms and maximally stimulated by 1.0 microgram/animal. Lesser stimulatory effects were observed 1 h after injection of 10 or 100 micrograms. At this 1 h point, the level of circulating estradiol was linearly increased relative to the 17 beta-estradiol dose. The level of nuclear form estrogen receptor was increased from 8% of the total receptor content in control rats to 12%, 28%, 50%, and 64% of the total receptor content in rats that received 0.1, 1.0, 10.0, and 100 micrograms, respectively. The anterior pituitaries of rats injected with 100 micrograms 17 beta-estradiol contained 30% fewer measurable estrogen receptors than control rats. Thus, dose-dependent losses of transcriptional responsiveness and measurable estrogen receptor were observed 1 h after injection of the larger doses of 17 beta-estradiol. Twenty four hours after injection of the various doses of 17 beta-estradiol, PRL gene transcription was stimulated 1.3-fold in response to 0.1 microgram and approximately 2-fold in response to 1.0, 10, and 100 micrograms. At the 24 h point the circulating level of this hormone and the levels of nuclear and cytosolic forms of the estrogen receptor had returned to near their control values. This differing dose responsiveness at 1 and 24 h supports our previously reported observation that estrogen regulates PRL gene transcription in vivo through at least two independent mechanisms. PMID- 2909368 TI - Triiodothyronine transport into differentiated and undifferentiated mouse neuroblastoma cells (NB41A3). AB - The mechanism of T3 entry into cells was studied in undifferentiated NB41A3 neuroblasts and after differentiation with 0.5 mM sodium butyrate. In undifferentiated neuroblasts, cell uptake of labeled L-T3 at 2 h was reduced to 43% of the control value by excess L-T3, whereas only 5.9% of D-T3 uptake was saturable. After incubation of intact cells with labeled hormone, the nuclei contained 3.8% of the total cellular L-T3 and 4.3% of D-T3. Thus, L-T3 nuclear uptake was 3 times higher than D-T3. Kinetic analysis of the initial rate of uptake of L-T3 by the cells gave a Km of 1.25 nM and a maximum velocity of 2.38 fmol/min.10(6) cells. The initial rate of D-T3 uptake was not saturable. Inhibitors of ATP production (antimycin and oligomycin) as well as monodansylcadaverine virtually abolished saturable cell uptake and decreased nuclear uptake more than total cell uptake, suggesting that the saturable component of uptake into the cells is the major source of nuclear L-T3. After differentiation by butyrate, both cell uptake and nuclear uptake of L-T3 increased. The apparent affinity (Ka) of the nuclear T3 receptors was determined in intact cells and compared with the Ka measured with isolated nuclei. In undifferentiated cells, the apparent Ka was 3-fold higher than the true Ka, presumably due to a step-up in the free T3 concentration in the cytosol compared to that in the incubation medium. After butyrate exposure, the apparent nuclear Ka was decreased to less than 1.5 times the control value, but Ka in isolated nuclei was unchanged. The number of nuclear receptors, however, was increased by butyrate in both intact cell and isolated nuclei experiments. These results indicate that butyrate exerts separate effects on the number of nuclear receptors and saturable T3 transport in mouse neuroblasts. PMID- 2909369 TI - Ontogeny of prolactin secretion in the neonatal rat is regulated posttranscriptionally. AB - PRL-secreting cells first appear in appreciable numbers on day 4 of neonatal life in rats. In the present study, we attempted to ascertain whether the ontogenic appearance of PRL mRNA and hormone release were temporally coordinated or discordant. Our results show that the PRL gene is expressed at least 3 days before the onset of secretion in newborn rats. Moreover, steady state levels of PRL mRNA in neonates are at least as high as those found in 10-day-old rats, in which 15-17% of all pituitary cells secret the hormone. This apparent blockage of translation is attributable to a lack of association of PRL message with ribosomes in the neonate. Taken together, these data indicate that the ontogeny of PRL secretion in rats is regulated translationally as well as transcriptionally. PMID- 2909370 TI - Regulatory effects of insulin-like growth factors I and II on bone collagen synthesis in rat calvarial cultures. AB - Insulin-like growth factors I and II (IGF-I and -II) are polypeptides secreted by skeletal cells and are considered regulators of bone formation. IGF-I and -II were studied for their effects on collagen synthesis and degradation in cultures of intact fetal rat calvariae and on type I collagen transcript levels in osteoblast-enriched (Ob) cells from fetal rat parietal bone. IGF-I and -II increased [3H]proline incorporation into type I collagen independently of their effect on cell replication. IGF-I and -II also decreased collagen degradation in calvarial cultures. Both factors had similar actions, although IGF-I stimulated collagen synthesis at 10 nM, and IGF-II at 30 nM. In Ob cells, IGF-I and -II also increased [3H]proline incorporation into type I collagen, but the effect was seen at 100 nM, and neither factor decreased collagen degradation. Slot blot analysis of IGF-I- and IGF-II-treated cells, using a rat type I collagen cDNA probe, revealed an increase in type I collagen transcripts. In conclusion, IGF-I and -II increase bone collagen synthesis and decrease collagen degradation in cultures of intact calvariae; the effect on collagen synthesis correlates with an increase in transcript levels in Ob cells. PMID- 2909371 TI - Actions of an estradiol-17-fatty acid ester in estrogen target tissues of the rat: comparison with other C-17 metabolites and a pharmacological C-17 ester. AB - The C-17 fatty acid esters of estradiol (E2) are a unique family of nonpolar estradiol metabolites. They are potent long-acting estrogens that represent the natural analog of the synthetic esters used for estrogen therapy. We measured the uterotropic response and the formation of uterine nuclear estrogen receptors (ERn) produced by iv administration of a representative ester, E2-17-stearate, in comparison to E2, other natural C-17 conjugates of E2, E2-17-glucuronide, and E2 17-sulfate, and the pharmacological ester E2-17-cyclopentylpropionate. While E2 17-stearate produced a sustained and greater uterotropic response compared to E2, the maximal induction of ERn by the ester was only about one third of that induced by a similar dose of E2. However, the induction of ERn by E2-17-stearate was markedly sustained compared to that by E2. Furthermore, the initiation of the ERn response to E2-17-stearate was delayed. Since E2-17-esters do not bind to the ER, this delay is consistent with the requirement for hydrolysis of the esters before interaction with the ER. Neither of the ionic conjugates of E2 (sulfate and glucuronide) produced an increase in ERn concentrations or a uterotropic response. The synthetic ester cyclopentylpropionate, like E2, produced a rapid ERn response and a significantly shorter uterotropic response than the stearate ester. When the induction of ERn by E2-17-stearate was investigated in other target tissues there were no marked differences in the brain, pituitary, and liver. No blood-brain barrier was apparent for the formation of ERn, despite the fact that this steroidal ester circulates in the blood bound to lipoproteins. These findings suggest that this unusual family of steroidal esters has biological properties that differentiate them from other known estrogens, natural and synthetic, in terms of their ability to produce a slow-onset sustained estrogenic stimulus in a variety of different estrogen target tissues. PMID- 2909372 TI - Progestin receptors in brain and pituitary of 20-day-old fetal mice: an autoradiographic study using [125I]progestin. AB - The distribution of progestin target sites in the brain and pituitary of estrogen primed 20-day-old fetal mice was investigated by thaw-mount autoradiography. Three pregnant mice were each implanted sc with a Silastic tube containing estrogen on day 17 and ovariectomized on day 19 of gestation. Twenty-four hours after ovariectomy 10 fetuses (5 males and 5 females) were collected and each injected sc with 0.33 microgram/100 g BW [125I]progestin (SA, 2200 Ci/mM). For competition, two additional fetuses were injected with 20 micrograms R5020 1 h before (Z)-17 beta-hydroxy-17 alpha-(2[125I]iodovinyl)4-estren-3-one [( 125I]Progestin) to demonstrate that nuclear uptake and retention of radioactivity were specific for progestin. Two hours after injection of [125I]Progestin all fetuses were mounted, frozen, and sectioned in a cryostat. After 1-37 days of exposure, sections were developed and scanned for labeled cells. Cells with nuclear concentration were found in the male and female preoptic area, within certain nuclear groups in the basal hypothalamus, in the central gray of the midbrain, and in the pituitary. No labeling was detected in the cortex or amygdala. The results indicate that cells in certain regions of the brain and pituitary express progestin receptors at the end of gestation and suggest that progesterone is important for the normal development of these cells. PMID- 2909373 TI - Direct modulation by estradiol of the response of human bone cells (SaOS-2) to human parathyroid hormone (PTH) and PTH-related protein. AB - We have investigated the actions of 17 beta-estradiol (E2) on the production of cAMP stimulated by synthetic human PTH [hPTH-(1-34)], synthetic hPTH-related protein [hPTHrP-(1-34)], and vasoactive intestinal peptide (VIP) in human (SaOS 2) and rat (ROS 17/2.8) osteoblast-like osteosarcoma cells. In SaOS-2 cells, hPTH (1-34) (2.5 nM), hPTHrP-(1-34) (2.5 nM), and VIP (10-100 nM) stimulated the accumulation of cAMP markedly (greater than 20- to 30-fold in 1 h). Cells were preincubated in serum-free medium for 4-24 h, then in the absence or presence of E2 for 4 h before a 1-h stimulation with peptide hormone in the absence of E2. In SaOS-2 cells, pretreatment with E2 (10(-12)-10(-8) M) for 4 h inhibited by up to 50% the accumulation of cAMP stimulated by hPTH-(1-34) or hPTHrP-(1-34), but E2 had no inhibitory effect on VIP action. 17 alpha-Estradiol had no inhibitory action on hPTH- or hPTHrP-stimulated accumulation of cAMP at concentrations as high as 10(-8) M. Additional evidence against a nonspecific effect of E2 was the total lack of inhibition of cAMP accumulation stimulated by hPTH-(1-34) or hPTHrP (1-34) in ROS 17/2.8 cells at concentrations of E2 up to 10(-6) M. We conclude that E2 can act directly and rapidly in human osteoblast-like cells to modulate selectively the ability of hPTH and hPTHrP to enhance the production of cAMP. PMID- 2909374 TI - Testosterone raises neuropeptide-Y concentration in selected hypothalamic sites and in vitro release from the medial basal hypothalamus of castrated male rats. AB - Although neuropeptide-Y (NPY)-containing neurons are widely distributed in the hypothalamus, castration decreased NPY concentrations only in the median eminence (ME), arcuate nucleus (ARC), and ventromedial nucleus (VMN). We have now examined the effects of testosterone (T) replacement in 2-week castrated male rats on NPY levels in hypothalamic and preoptic area regions and in vitro NPY release in three experiments. In the first experiment we studied the effect of T on NPY concentration in castrated rats. Two-week castrated rats were implanted sc with T filled or empty Silastic capsules 30 mm in length. Ten days later rats were killed, and NPY levels were measured by RIA in microdissected sites. T implants raised serum T levels to the range found in gonad-intact rats and decreased serum LH levels to the basal range. Further, of the six brain sites examined, significant increases in NPY concentrations occurred selectively in the ME, ARC, and VMN of T-implanted rats. In the second experiment, the ability of T to reverse the effect of castration on NPY levels compared to those in intact (sham) rats was assessed. Again, castration decreased NPY levels in the ME, ARC, and VMN only, and replacement of physiological levels of T restored NPY levels approximately 100%, 127%, and 74% in the ARC, VMN, and ME, respectively. In the third experiment, the effect of castration and T implants (30-mm T capsules for 10 days) to 2-week castrated rats on the in vitro release of NPY from medial basal hypothalamus (MBH) was assessed. Basal NPY release was not significantly changed after castration and T replacement. However, in response to a 30-min pulse of KCl (45 mM) NPY release from the MBH of castrated rats was significantly reduced compared to that in intact and T-replaced castrated rats. These studies show that castration decreases and T replacement restores NPY levels selectively in three hypothalamic sites, viz. ME, ARC, and VMN, and KCl-induced NPY release from the MBH in vitro is decreased after castration and restored by T replacement, thereby suggesting that a local subset of androgen-concentrating neurons may regulate NPY levels and release in a site-specific manner. Further, these results are in line with our emerging view that gonadal steroids modulate neurosecretion not only of LHRH, but also of other functionally linked regulatory peptides. PMID- 2909375 TI - Glucocorticoid receptors and glucocorticoid effects in rat Sertoli cells. AB - In this report we demonstrate glucocorticoid receptors in seminiferous tubules of the rat testis, and that these receptors are localized in Sertoli cells and peritubular cells. The receptors had high affinity for [3H]dexamethasone (Kd = 0.5 - 1 x 10(-9) M), and similar Kd values were calculated from equilibrium analysis and from rate studies (k1 = 1.5 x 10(6) M-1 min-1 and k-1 = 1.4 x 10(-3) min-1, O C). Binding specificity was typical for glucocorticoid receptors (affinity: dexamethasone greater than corticosterone greater than cortisol approximately R5020 approximately progesterone greater than aldosterone = R1881 greater than 17 beta-estradiol approximately cortisone approximately testosterone greater than 5 alpha-dihydrotestosterone). The concentration of glucocorticoid receptors in rat seminiferous tubules revealed an age-dependent decrease, coinciding with the increase in the number of germ cells. Glucocorticoid receptor levels were higher in Sertoli cells from immature rats than in cells from adult rats. Cultured peritubular cells from immature rats contained levels of glucocorticoid receptors similar to cultured Sertoli cells from rats of the same age. With a nick-translated human glucocorticoid receptor complementary DNA probe, a messenger RNA (mRNA) species of approximately 7 kilobase was clearly detected in both Sertoli cells and peritubular cells. In peritubular cells, a smaller mRNA species (5 kilobase) was also clearly detectable. In mRNA from whole testis tissue, a similar developmental pattern as for dexamethasone binding was found. Dexamethasone caused a concentration-dependent stimulation of mRNA levels for androgen binding protein and for the cAMP-dependent protein kinase regulatory subunit type II beta in cultured immature rat Sertoli cells. On the other hand, mRNA levels for glucocorticoid receptor decreased, whereas mRNA levels for beta actin remained constant. This report documents for the first time the presence of glucocorticoid receptors and glucocorticoid effects in rat Sertoli cells, and is also the first demonstration of glucocorticoid receptors in peritubular cells of the rat testis. PMID- 2909376 TI - Aromatase activity in quail brain: correlation with aggressiveness. AB - Testosterone (T) triggers aggressive behavior in males of many vertebrate species; however, the neural and hormonal basis of individual differences in the frequency or intensity of aggressive behavior is still debated. Using the Japanese quail (Coturnix coturnix japonica), a species in which individuals exhibit a wide range of aggressiveness in nature and the laboratory, together with a newly devised test procedure for quantifying aggressiveness, we recently demonstrated that aggression is estrogen dependent. Here we extend these studies by testing the hypothesis that aromatization in brain is a rate-limiting step in the expression of individual differences in aggressiveness. Using procedures previously validated for this species, aromatase and 5 alpha- and 5 beta reductase activities were estimated in selected brain regions of reproductively active male quail by measuring conversion of [3H]androstenedione to [3H]estrone, [3H]5 alpha-androstanedione, and [3H]5 beta-androstanedione, respectively. In Exp 1, behaviorally inexperienced test birds were killed 90 sec after a single behavioral test. Aggressiveness of individuals in this group, as determined by pecking and locomotor activity in response to visualization of a conspecific, ranged 3- to 4-fold from high to low. Aromatase activity in the posterior hypothalamus (PHYP) was significantly higher in males rated high for aggressiveness than in animals rated low (1.04 vs. 0.59 pmol/h.mg protein; P less than 0.02). Similar differences were observed in the anterior hypothalamus/preoptic area (AHPOA) but were not significant. In Exp 2, sexually mature males were behaviorally tested eight times over 22 days and killed 24 h after the final test. Aggressiveness varied 5-fold from high to low, although the rating in a given bird remained constant with time and repeat testing. Aromatase activity in the AHPOA was significantly greater in birds rated high for aggressiveness than in low aggressiveness birds (3.77 vs. 2.80 pmol/h.mg protein; P less than 0.02). In addition, when AHPOA aromatase in all birds was plotted against behavioral intensity, there was a 2-fold variation and a significant positive correlation (r = 0.556; P less than 0.02). Similar differences were observed in PHYP, but these were of borderline significance. By contrast, aromatase levels outside the AHPOA and PHYP were unrelated to behavior. Moreover, in both Exp 1 and 2, 5 alpha- and 5 beta-reductase activities in AHPOA, PHYP, and other brain regions; plasma T, 5 alpha-dihydrotestosterone, and total estrogens; and relative testicular weights were not consistently related to aggression.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2909377 TI - Uptake of cortisol by the perfused rat liver: validity of the free hormone hypothesis applied to cortisol. AB - The mechanism by which cortisol in plasma enters hepatic cells was investigated using the isolated perfused rat liver. To determine whether hepatic uptake of cortisol from serum can be accounted for entirely by the pool of unbound (free) cortisol, we compared observed uptake rates with the equilibrium-free fraction of cortisol in serum and the rates of dissociation of cortisol from its serum binding proteins (determined using a rapid filtration assay based on transfer of [3H] cortisol to dextran-coated charcoal). More than 95% of the cortisol in both human and rat serum dissociated spontaneously from its binding proteins within 5 sec at 37 C. The fractional unidirectional hepatic uptakes of cortisol from pooled human serum and pooled rat serum were 59.4 +/- 5.4% and 59.5 +/- 1.0% (mean +/- SE), respectively, at the physiological flow rate of 1 ml/min.g liver. The corresponding free cortisol fractions in these sera were 4.53 +/- 0.15% and 8.16 +/- 0.23%, respectively. The fractional unidirectional hepatic uptake of cortisol from protein-free buffer averaged 99.9% (n = 5) at a flow rate of 3 ml/min.g liver. By calculating the appropriate rate constants and applying the Kety-Renkin-Crone equation to the above data, it can be shown that all of the cortisol taken up from serum by the perfused rat liver can be accounted for by the pool of free cortisol, which turns over very rapidly. The physiological significance of this finding is discussed in terms of a general mathematical model of hormone transport that delineates the conditions under which the free hormone hypothesis is and is not valid. PMID- 2909378 TI - Enhancement of cytosolic tyrosine kinase activity by propylthiouracil-induced hyperplasia in the rat thyroid. AB - Hyperplasia of the thyroid gland induced by propylthiouracil (PTU) is a well established model of rapid cell proliferation in vivo. Recent evidence indicates that tyrosine kinase activity is associated with growth factor receptors and oncogene protein products and may have an important regulatory action in the control of cell growth. Thus, we examined tyrosine kinase activity in rat thyroid membrane and cytosol preparations at rest and during PTU-induced hyperplasia. Although kinase activity was present in a crude microsomal membrane preparation, no change was observed during thyroid growth. In contrast, tyrosine kinase activity assayed with the artificial substrate poly(Glu,Na:Tyr) 4:1 was present in normal rat thyroid cytosol and increased 2- to 6-fold during the rapid phase of hyperplasia in the first 5-10 days of PTU treatment. It declined to control values by day 15, when the size and DNA content of the thyroid reached a plateau. Preincubation of the cytosolic preparations with several peptides known to bind to and activate growth factor receptor tyrosine kinases failed to enhance the activity, suggesting, along with the cytosolic localization, that the activity was distinct from these receptors. By gel filtration chromatography and polyacrylamide gel electrophoresis, tyrosine kinase activity was associated with a 55 kDa protein. Partial purification over a poly(Glu,Na:Tyr)4:1-Sepharose column, yielded a protein that appeared capable of autophosphorylation. It is suggested that this tyrosine kinase plays a role in mediating the growth promoting effects of this model of thyroid cell hyperplasia. PMID- 2909379 TI - Role of dopamine and vasoactive intestinal peptide in the control of pulsatile prolactin secretion. AB - The present studies were designed to obtain a detailed characterization of pulsatile PRL secretory patterns under basal conditions and to explore the role of dopamine (DA) and vasoactive intestinal peptide (VIP) in the genesis of PRL pulses. Adult intact male rats received chronic indwelling jugular canula and were bled at 3-min intervals for periods ranging from 90-150 min. Pulse analysis was performed using the algorithm Detect. Blockade of DA receptors with domperidone, pimozide, or haloperidol resulted in a 2-fold increase in PRL pulse frequency, with no change in pulse duration. All quantitative parameters, i.e. peak and trough values, pulse amplitude, and area under the pulse, were significantly increased after dopaminergic blockade. Blockade of endogenous VIP activity was achieved by passive immunization with a potent VIP antiserum. This treatment, by itself, did not modify basal PRL levels or PRL pulsatility parameters. However, when VIP antiserum was administered in combination with domperidone, a reduction in all quantitative pulse parameters was observed. Heterogeneity of PRL pulses was evaluated by frequency distribution analysis, using the area under the pulse divided by basal secretion, to evaluate the mass of hormone secreted per pulse normalized to the basal rate of secretion. Untreated animals presented pulses within a range of different masses. Dopaminergic blockade resulted in a great reduction in big mass pulses, and the distribution of pulses was restricted primarily to small mass pulses. The increased pulse frequency after dopaminergic blockade, therefore, results mainly from an increase in the appearance of small mass pulses. These results indicate that DA exerts a tonic inhibitory action on the frequency as well as the qualitative parameters of PRL pulses. They also suggest that big mass PRL pulses are dopaminergic in origin, i.e. they may result from temporary interruptions in DA activity. Small mass PRL pulses appear to result from other neural stimulatory inputs. Endogenous VIP enhances quantitative PRL pulse parameters, but this activity is only apparent after removal of DA inhibition. PMID- 2909380 TI - Distinct pulsatile prolactin secretory patterns during the estrous cycle: possible encoding for diverse physiological responses. AB - PRL levels during the estrous cycle have been reported to be low, with the notable exception of the afternoon proestrous surge. The present study was designed to evaluate the pulsatile pattern of PRL secretion during the low secretory phases of the cycle. Animals were bled at 3-min intervals for 150 min during proestrus morning (AM), estrus AM and evening (PM), metestrus AM, and diestrus AM and PM. Using the algorithm Detect, pulse frequency, duration, interval, peak and trough values, area under the pulses, and mean PRL levels were calculated. PRL secretion was pulsatile during all stages of the estrous cycle, although the pattern varied considerably among the different cycle stages. Pulse frequency was highest during estrus and lowest during diestrus. All quantitative pulse parameters (peak, trough, amplitude, and area under pulse) were also higher during estrus and lowest in diestrus. Analysis of area under the pulse using frequency distribution indicated that at least two subpopulations of pulses, i.e. small mass and large mass pulses, were observed in certain stages of the cycle. Small mass pulses were present at all stages of the cycle; while their frequency remained unchanged, changes in other parameters were observed at different stages which did not always correlate with changes in mean PRL levels. Big mass pulses, on the other hand, presented a clear change in pulse frequency with values rising progressively from diestrus PM through proestrus to peak at estrus. Between estrus PM and metestrus AM these big mass PRL pulses essentially disappeared. In contrast to the marked changes in frequency, big mass PRL pulses were remarkably homogeneous in other quantitative characteristics. The results indicate that distinct changes in PRL pulsatility patterns occur during the estrous cycle; these changes are related to both the pattern and the quality of PRL pulses. Based on the observations of a companion study (28) and other data, we suggest that the genesis of the big mass and small mass PRL pulses involves dopaminergic and nondopaminergic mechanisms, respectively. The timing and selectivity of the changes in PRL pulsatile patterns suggest that those patterns may encode different signals for expression of the diverse actions of PRL on reproductive tissues. PMID- 2909381 TI - Prostaglandin F2 alpha administered in vivo induces Ca2+-dependent protein phosphorylation in rat luteal tissue. AB - The present study was performed in order to further elucidate the mechanism of action of PGF2 alpha in luteolysis in the rat ovary. Seven days after priming with superovulatory doses of pregnant mare serum gonadotropin and human chorionic gonadotropin to induce luteal tissue formation, the rats were injected with a luteolytic dose of the prostaglandin F2 alpha analogue cloprostenol. The ovaries were then homogenized, a 30,000 x g supernatant and pellet were prepared, whereafter aliquots of the preparations were incubated in the presence of [gamma 32P]ATP with or without Ca2+. The phosphorylated proteins were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis and localized by autoradiography. The presence of Ca2+ caused an increased phosphorylation of a 45 kDa protein band in the particulate, but not in the cytosol, fraction. Furthermore, PGF2 alpha rapidly increased the 32P incorporation into the same protein band of 45 kDa. Thus, the PGF2 alpha-stimulated 32P incorporation was Ca2+-dependent and seen only in the particulate fraction. These results suggest that PGF2 alpha in its role as a luteolytic agent stimulates a Ca2+-dependent phosphorylation of a specific protein in luteal membranes of the rat ovary. PMID- 2909382 TI - The aged rat model of ovarian hormone deficiency bone loss. AB - Three studies were carried out. First, the effects of aging on the maturation of the female skeleton were assessed. Second, the hypothesis that has linked ovarian hormone deficiency bone loss to hypercalcemic suppression of the parathyroids leading to a decrease in 1,25-dihydroxyvitamin D synthesis and gut absorption of calcium was examined. Third, the effects of ovariectomy and a combination of ovarian hormone deficiency and low dietary calcium on bone and the calcium regulating hormones were evaluated. After 6 months, ovariectomy and a low calcium diet independently decreased the density of the ilium, the femur, and the fourth lumbar vertebra as well as the calcium content of the latter two. The effects of the two treatment regimens were additive and more marked in the vertebral bone. Ovariectomy lowered serum calcitonin only in animals fed a normal diet and had no effect on serum PTH and vitamin D metabolites, while a low calcium diet caused a significant increase in serum 1,25-dihydroxyvitamin D. In both dietary regimens ovariectomy resulted in about a 30% decrease in intestinal calcium absorption. A low calcium diet increased morphometric indices of bone formation and bone resorption as did ovariectomy, with resorption exceeding formation. The discussion of our findings led to the conclusion that the aged rat model of ovarian hormone deficiency bone loss qualifies for serious consideration as a practical convenient cost-effective animal model for exploring aspects of the pathogenesis and treatment of postmenopausal bone loss. PMID- 2909383 TI - Flow cytometric measurement of intracellular pH in B16 tumors: intercell variance and effects of pretreatment with glucose. AB - Flow cytometry was used to measure cytoplasmic pH (pHi) of B16 melanoma cells taken from tumor-bearing animals. We used a ratiometric method to allow measurements on an individual cell basis which were independent of cellular content of the pH indicator BCECF. In order to "freeze" any intercell variance which may have existed within the tumor mass, tumors were mechanically disaggregated in bicarbonate-free medium containing 0.5 mM amiloride at 4 degrees C and loaded with BCECF in choline chloride-based Earle's solution at 37 degrees C. Studies using cells grown in vitro showed that this protocol prevented acid load recovery during the 30-min period typically required between tumor excision and pHi measurement. A calibration curve was obtained by resuspending BCECF stained cells in a range of buffers containing the proton ionophore nigericin. The range of values for individual cells was estimated by comparing the coefficient of variation of the test sample with that obtained when nigericin was used to reduce all cells to the pHi of the calibration buffer. The average value for mean tumor cell pH was 7.32 +/- 0.05 SD. Pretreatment of animals with intraperitoneal glucose for one hour resulted in an average for mean pHi of 7.17 +/- 0.17 SD. Mean coefficient of variation was 8.7%, and in the presence of nigericin, 8.1%. These values indicate a variance in measured pHi of approximately +/- 0.4 pH units, but most of this results from experimental error rather than true intercell pHi variance. The method used here is capable of detecting reduction in mean tumour pHi caused by ip glucose, but incapable of precise estimation of individual cell values. Despite these uncertainties, the results suggest that the range of pHi within B 16 tumors is small. PMID- 2909384 TI - Growth in retinal glial cells in vitro is affected differentially by two types of cell contact-mediated interactions. AB - Contact among rabbit retinal glial cells in subconfluent culture was previously shown to stimulate DNA synthesis [J. M. Burke (1983) Exp. Cell Res. 146, 204 206]. In this study nonliving surface membranes and metabolic coupling were investigated as mediators of the contact-dependent phenomenon. To evaluate surface membranes, preparations of fixed glial cells and fixed fibroblasts of several types were added in varying numbers to sparse cultures of glia or fibroblasts. In agreement with published data, fibroblast proliferation was inhibited by the fixed cells in a dose-dependent manner. Growth in glial cells was similarly inhibited. Fixed cells of both types were approximately equally effective in suppressing proliferation in cells of both types. No number of fixed cells was identified which, when added to glial cultures, stimulated glial proliferation. In contrast, metabolic coupling among glial cells was associated with increased DNA synthesis. Coupling was detected radioautographically as a flux of labeled precursor molecules from a prelabeled to a recipient population of glial cells in coculture. The cocultures were secondarily incubated with [3H]thymidine to label the nuclei of S-phase recipient cells. In the cocultures there was a higher rate of nuclear labeling in coupled than in uncoupled recipient glial cells. The results suggest that growth in subconfluent retinal glial cell cultures is modulated differentially by two types of interactions which require cell contact: growth is inhibited by interaction among nonliving cell surfaces but stimulated by metabolic cooperation among living cells. PMID- 2909385 TI - Growth cone advance mediated by fibronectin-associated filopodia is inhibited by a phorbol ester tumor promoter. AB - In serum-supplemented medium, exposure to the tumor promoter 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA) increases the proportion of SH-SY5Y neuroblastoma cells with neurites and increases the average neurite length. In the present study, under serum-free conditions, PMA treatment had the opposite effects, i.e., retarded neurite sprouting and partially inhibited neurite elongation. This inhibition in neurite outgrowth was partially antagonized by the addition of serum fibronectin (FN) to the medium or substratum. In the absence of PMA, SH-SY5Y cells grown under serum-free conditions showed extensive neurite outgrowth as well as the capacity to secrete FN into their microenvironment and form FN-containing substratum-attachment sites. Immunogold labeling and whole mount transmission electron microscopy (WMTEM) demonstrated FN-containing contact pads at sites where filopodia attached to the substratum and focal plaques on the underside of growth cone margins. The appearance and abundance of FN-containing contact pads and focal plaques were increased by the addition of exogenous FN to defined medium. Focal plaques appeared in close association with microfilament bundles, and nearly always with bundles that projected into filopodia attached to the substratum by contact pads. A method for immunolabeling FN in the filopodial contact pads of living cultures provided more direct evidence that filopodia and contact pads have a major role in FN-mediated attachment and are central in determining growth cone shape and the rate and direction of advance. In support of this view, we show that PMA treatment retards neurite sprouting, alters growth cone morphology and motility, and eliminates the appearance of microfilament bundles, filopodia, and FN-containing substratum-attachment plaques. PMID- 2909386 TI - DNA amplification in arsenite-resistant Leishmania. AB - Arsenite-resistant variants of a trypanosomatid protozoan, Leishmania mexicana amazonensis, were selected in vitro by stepwise increases of sodium arsenite concentrations up to 30 microM in the culture medium. These variants were found to contain amplified DNA as extrachromosomal supercoiled molecules of about 69 kb. They originate from a single chromosome in the wild-type cells. There is evidence of chromosomal changes in these cells associated with the selection for arsenite resistance. The apparent absence of these circular molecules in the wild type and their loss from the drug-sensitive revertants suggest amplification of chromosomal DNA into these extrachromosomal circles as the mechanism of arsenite resistance. PMID- 2909387 TI - Glycoprotein glycans may not be necessary for the differentiation of skeletal myoblasts. AB - Previous work using glycosylation inhibitors has suggested that high-mannose type but not complex type oligosaccharides on the surface of cells may play a role in the differentiation of skeletal myoblasts. Earlier, we had shown that a concanavalin A-resistant mutant derived from an L6 myoblast line fails to differentiate in a medium containing 10% horse serum. Here we show that one such concanavalin A-resistant mutant (D-1) which was reported to have oligosaccharides of the type Man(3-5)G1cNAc2, shows significant fusion ability when grown in media containing 1% horse serum. Lowering the serum concentration did not alter the dolichol-phosphate mannosyltransferase activity in D-1 which remained at low levels compared to L6. The incorporation of [3H]mannose in D-1 was found to be 60% of L6 in 10% serum whereas in 1% serum the incorporation into D-1 was further reduced to 30% of L6. [3H]mannose-labeled ConA-binding proteins isolated from L6 were quantitatively and qualitatively similar in cells grown in either 10 or 1% serum. However, in D-1 cells a further decrease in the ConA-binding ability of these glycoproteins was observed. Biochemical differentiation also occurs in D-1 upon fusion in 1% serum as seen by the increase in mRNA levels of the muscle specific markers myosin light chain and troponin T. These results suggest the high-mannose type of oligosaccharides may not be involved in myoblast differentiation. PMID- 2909388 TI - Retinoic acid induces a specific membrane glycoprotein in human epithelial cell lines. AB - Retinoic acid (RA) inhibits growth, increases the cytokeratin content, and alters the cytoskeleton of the human cervical cell line NHIK 3025. Using RA-treated NHIK 3025 cells as immunogen we prepared murine monoclonal antibodies (IgG1) which recognized an RA-induced cell-surface antigen which could not be detected in untreated NHIK 3025 cells. Analysis of the Triton soluble proteins by SDS-gel electrophoresis and immunoblotting revealed that the cell-surface antigen is a 140-kDa glycoprotein (gp140). gp140 was also shown to be induced by RA in HeLa S3 cells and constitutively expressed in the human trophoblast cell line BeWo. gp140 was also detected in other human epithelial cell lines, but not in human hematopoietic cells. Expression of gp140 was induced in HeLa S3 cells by nanomolar concentrations of RA, and in NHIK 3025 cells by micromolar amounts (1 10 microM). The glycoprotein was detectable 3-6 h following exposure to RA and its expression was reversible upon removal of RA from the medium. Our results indicate that gp140 is a newly identified RA-inducible epithelial membrane glycoprotein which may represent a phenotypic differentiation marker for epithelial cells. PMID- 2909389 TI - Chromatin reorganization during emergence of malignant Friend tumors: early changes in H2A and H2B variants and nucleosome repeat length. AB - Serial examination of five newly derived Friend murine tumors during early subcutaneous passages showed continuing changes in chromatin composition and structure over the first 10 to 20 passages followed by a period of stabilization over the subsequent 20 passages. These changes were reflected in a decrease in two major histone variants, H2A.1 and H2B.2, with a coordinate increase in histone variants, H2A.2 and H2B.1, and a changing nucleosome repeat length (NRL). The absolute values differed among the five tumors, but all five showed the same general direction of change. There was no obvious relationship among the NRL, H2A, and H2B histone variant values. A low H2A.1/H2A.2 ratio was found in Friend tumors of high malignant potential. Cell lines derived in vitro also showed directional changes in the H2A and H2B variants similar to those of their tumor cell parents, but with different kinetics. Our findings suggest that Friend tumor establishment is accompanied by an early period of chromatin reorganization marked by changes in several parameters of chromatin structure. PMID- 2909390 TI - Effect of aging on populations of estrogen receptor-containing cells in the rat uterus. AB - Estrogen receptor-containing cells were identified in uteri of mature and senescent rats by means of quantitative autoradiography. Cell numbers and density were assessed in the various uterine layers. It was determined that despite decreases in receptor concentrations in endometrium, endometrial stroma, myometrium, and epithelium, no significant cell loss occurred in any region. Receptor content per cell clearly decreased with age in the endometrial stroma, while only in the myometrium was there any suggestion of cell loss in the absence of receptor loss from individual cells. Thus, age-related reductions in uterine estradiol receptor levels may be due to different mechanisms in different tissue regions. PMID- 2909391 TI - Low intensity microwave radiation effects on the ultrastructure of Chang liver cells. AB - Chang liver cells (CCL-13 ATCC) exposed to 2450 MHz microwaves of field intensities ranging from 5 to 20 mW/cm2 for different periods up to 2 h show distinct alterations in the cytomembrane ultrastructure. A 30-min exposure of 10 mW/cm2 produces well-defined cytoplasmic lesions which appear as clear areas of degenerated rough endoplasmic reticulum (RER). Extensive degeneration of RER along with fragmentation and vacuolation, disorganization of mitochondrial membranes and matrix, increased lysosomal activity, and in some cases disruptions of nuclear membrane are seen in longer exposures. Radiation at 20 mW/cm2 produces significant damage to cell membranes in short exposures and treatments of 30 min and longer exposures lead to total disruption of organized cell ultrastructure. The identity of many organelles is lost as the cells become highly heteropycnotic with numerous cytoplasmic projections. Short exposures of 5 mW/cm2 produce very few noticeable differences in ultrastructure. These results confirm earlier observations that membranes may be the primary targets of microwave radiation in cells. PMID- 2909392 TI - Cloning and sequence of a secretory protein induced by growth factors in mouse fibroblasts. AB - From a collection of 80 cDNAs representing genes that are induced by serum growth factors in quiescent mouse fibroblasts we have characterized a clone, N51, and demonstrated that it codes for a precursor of a secretory protein. N51 mRNA is rapidly induced by serum, including in the presence of cycloheximide, demonstrating that its induction does not require de novo protein synthesis. The mRNA has a short half-life of approximately 10-15 min and is dramatically prolonged in the presence of protein synthesis inhibitors. Purified growth factors such as platelet-derived growth factor and bombesin are strong inducers of N51 expression. However, epidermal growth factor, fibroblast growth factor, and the tumor promoter tetradecanoyl phorbol acetate have a negligible effect. Transcriptional analysis demonstrates that the increase in N51 mRNA levels after serum stimulation is in part due to the activation of gene transcription. PMID- 2909393 TI - Induction of the major inducible 68-kDa heat-shock protein after rapid changes of extracellular pH in cultured rat astrocytes. AB - Cultured rat astrocytes were exposed for 1 or 3 h to acidic medium (pH adjusted to 5.0, 5.5, or 6.0). Radioactive labeling for 3 h after exposure to acidic medium revealed increased synthesis of many proteins, including an inducible 68 kDa protein. Optimal extracellular (medium) pH for the induction of this 68-kDa protein was 5.5. Immunoblotting demonstrated that this 68-kDa protein induced by acidosis was the 68-kDa heat-shock protein previously described in cultured astrocytes. PMID- 2909394 TI - Production and response to an autologous growth factor isolated from human leukemia cells. AB - Human myeloid leukemia HL-60 cells have been shown to release into culture medium an activity that promotes the proliferation of these same HL-60 cells. The presence of additional culture supernatant containing growth-promoter activity accelerates the HL-60 growth rate as determined by cell counts and [3H]thymidine uptake. Isolation of this growth promoter has been performed with the serum-free supernatant of HL-60 cells using salt precipitation, DEAE-Sepharose ion exchange chromatography, and gel electrophoresis. The promoter activity was recovered from SDS-gel electrophoresis within the 60- to 85-kDa mol wt range where a single band of an apparent mol wt of 72,000 was demonstrated. The ability of HL-60 cells to respond to the growth promoter was significantly lost 4 h after exposure to differentiation-inducing activity, while production of the growth promoter was diminished only after 2-3 days following induction of differentiation. These results suggest that the growth-promoting mechanism is associated with the undifferentiated leukemic state. In addition, the role of an autocrine growth mechanism in maintaining the leukemic cells in an undifferentiated state is discussed. PMID- 2909395 TI - Relation between the rate of cell movement under agarose and the positioning of cells in heterotypic aggregates. AB - Single-cell suspensions prepared from 9-day-old chick tissues (skeletal muscle, liver, and neural retina) were used to investigate a possible relationship between intrinsic mobilities of different cell types and their positioning behavior in mixed (heterotypic) cellular aggregates. The relative mobilities of the three cell types, determined by comparing their ability to migrate under an agarose layer, was muscle greater than liver greater than neural retina. The gyratory shaker method was employed to produce heterotypic aggregates from mixed suspensions of muscle, liver, and neural retina cells and the tissue-specific positioning of cells after 24 h in culture was determined from histological and autoradiograph sections. The hierarchy for "inside" positioning of segregated cells was muscle greater than liver greater than neural retina cells, correlating with the rate of movement of these cells in the migration assay. The implication of the results is that relative speed of movement may determine the positioning of cells in heterotypic aggregates. PMID- 2909396 TI - Selective enrichment and biochemical characterization of seven human skin fibroblasts cell types in vitro. AB - The mitotic and postmitotic populations of the human skin fibroblast cell line HH 8 are heterogeneous when studied in vitro. There are reproducible changes in the frequencies of the mitotic fibroblasts (MF), MF I, MF II, MF III, and the postmitotic fibroblasts (PMF), PMF IV, PMF V, PMF VI, and PMF VII. For biochemical characterization, methods for selective enrichment of homogeneous populations of these seven fibroblast cell types have been established. Clonal populations with 95% purity for the mitotic fibroblasts MF I, MF II, and MF III can be raised in uniform clone types of fibroblasts (CTF) CTF I, CTF II, and CTF III. Pure clonal subpopulations of MF I type cells are present in mass populations in the range of 1-20 cumulative population doublings (CPD). Populations of mitotic fibroblasts represent nearly homogeneous populations of MF II (75-85% purity) in the range of 28-34 CPD and MF III (73-86% purity) in the range of 48-53 CPD. These populations can be easily expanded to up to 10(7)-10(8) cells. The spontaneous transition of MF III to PMF VI takes 140-180 days. In order to shorten this period and increase the proportion of distinct postmitotic types, mitotic fibroblast mass populations (CPD 30-32, MF II: 75-85% purity) have been induced by uv-irradiation to differentiate to nearly homogeneous populations of PMF IV, PMF V, PMF VI, and PMF VII within 4 to 36 days of culture. Using this method, 10(7) cells of one differentiation stage can be obtained. Spontaneously arising and experimentally selected or induced homogeneous clonal and mass populations of MF I, MF II, MF III, PMF IV, PMF V, PMF VI, and PMF VII express an identical differentiation-dependent and cell-type-specific [35S]methionine labeled polypeptide pattern. PMID- 2909397 TI - Metabolic behaviors of the core histones in proliferating Friend cells. AB - This study examines the turnover of the core histones in proliferating Friend cells. It was calculated that these proteins turn over with half-lives of 21.6 days for H2A, 13.8 days for H2B, 43.3 days for H3, and 138.6 days for H4. The significant differences in the half-lives of the four core histones indicate that the protein moiety of the nucleosome is not replaced as one entire unit but as a "mosaic" in which each component follows its own rate of replacement. In some experiments the turnover rates of the variants of H2A, H2B, and H3 were compared. The results did not indicate any differences among these histone variants, suggesting that they are not excluded from the mechanisms controlling histone turnover. Metabolic heterogeneity was discovered, however, when the turnover rates of the acetylated and nonacetylated molecules of histone H4 were followed: it appeared that the acetylated molecules are replaced 2.5 times faster. The comparison of the rate of replacement of the histones in proliferating and differentiated cells from one site and their level of acetylation from another suggests that this postsynthetic modification might be involved in the control of histone metabolism. Such a conclusion is supported also by a number of model experiments. PMID- 2909398 TI - Replication of Xenopus erythrocyte nuclei in a homologous egg extract requires prior proteolytic treatment. AB - Reactivation and reinitiation of DNA replication in quiescent frog erythrocyte nuclei has been analyzed following incubation in extracts prepared from activated Xenopus eggs. Nuclear decondensation and DNA synthesis only occurred if nuclei were pretreated with low doses of trypsin. This protease treatment did not digest histones, but did degrade several nonhistone proteins. Activated erythrocyte nuclei swell and begin DNA synthesis by 30 min after being mixed with the egg extract. In some extracts virtually complete genome replication was achieved in all nuclei after 2-3 hr. Addition of several protease inhibitors during sperm nuclear isolation significantly reduced the template efficiency of these preparations. We concluded that proteolytic alteration of nonhistone nuclear structural proteins may be a general mechanism which permits quiescent nuclei to reenter the replication cycle. Erythrocyte nuclei and egg extracts provide an excellent experimental system in which to investigate the processes of nuclear reactivation. PMID- 2909399 TI - Development and hormone regulation of androgen receptor levels in the sexually dimorphic larynx of Xenopus laevis. AB - Development of the sexually dimorphic larynx in African clawed frogs is controlled by secretion of androgenic steroids (D. Sassoon and D. Kelley, 1986, Amer. J. Anat. 177, 457-472). Adult laryngeal muscle shows high levels of androgen binding relative to other skeletal muscles and binding activity in males is three times that in females (N. Segil, L. Silverman, and D. Kelley, 1987, Gen. Comp. Endocrinol. 66, 95-101). To determine when androgen sensitivity and sex differences arise, we assayed [3H]dihydrotestosterone (DHT) binding activity in larynges from metamorphic and postmetamorphic male and female frogs. Scatchard analyses indicate that DHT binds to a saturable component with high affinity. At metamorphosis, male and female juveniles have average binding levels of 262 and 269 fmoles/mg protein, respectively, approximately 7 to 20 times their adult values. At 3 months postmetamorphosis (PM), sexually dimorphic binding levels are observed. Binding activity declines gradually in females from metamorphosis to 9 months PM. In males, levels of binding activity remain high throughout the first 6 months PM and then decrease to near adult levels by 9 months PM. Administration of exogenous DHT to 3 months PM juveniles decreases average binding activity from 180 (male) or 74 fmoles/mg (female) to 33.5 fmoles/mg in both sexes. Testosterone has a less pronounced effect on binding activity in males than DHT and is ineffective in females. We conclude that sexually dimorphic adult levels of androgen binding in larynx arise by differential decrease from initially high, sexually monomorphic levels and that high titers of circulating androgens normally present by 6 months PM in males are responsible for the marked decrease in binding activity observed during laryngeal development. PMID- 2909400 TI - The coelomic envelope of Xenopus laevis eggs: a quick-freeze, deep-etch analysis. AB - The extracellular matrix of Xenopus laevis oocytes was analyzed before and after meiotic maturation using quick-freeze, deep-etch, rotary-shadow electron microscopy. The perivitelline space (PS) of the meiotically immature oocyte contains a filamentous network which connects microvilli (MV) and follicle cell macrovilli to the folded oocyte surface below. The envelope overlying the PS is composed of bundles of large fibers which course between the tips of the MV. Spaces between these bundles contain smaller fibrils which secure the egg envelope to the microvillar tips. Meiotic maturation is accompanied by flattening of the oocyte plasma membrane, formation of an orderly array of MV, and elevation of the egg envelope. In the coelomic eggs, the reorganized envelope is composed of loosely bundled large fibers which course above the microvillar tips rather than between them. The spaces between these bundles contain small fibers similar to those seen in the meiotically immature oocyte. This reorganized envelope, however, will not bind sperm; further modifications must transpire during passage through the oviduct to render it sperm receptive. PMID- 2909401 TI - An embryo-lethal mutant of Arabidopsis thaliana is a biotin auxotroph. AB - Lethal mutants have been used in a variety of animal systems to study the genetic control of morphogenesis and differentiation. Abnormal development has been shown in some cases to be caused by defects in basic cellular processes. We describe in this report an embryo-lethal mutant of Arabidopsis thaliana that can be rescued by the addition of biotin to arrested embryos cultured in vitro and to mutant plants grown in soil. Mutant plants rescued in culture produced phenotypically normal seeds when supplemented with biotin but became chlorotic and failed to produce fertile flowers in the absence of biotin. Arrested embryos were also rescued by desthiobiotin, the immediate precursor of biotin in bacteria. Langridge proposed 30 years ago (1958, Aust. J. Biol. Sci. 11, 58-68) that the scarcity of plant auxotrophs might be caused by lethality prior to germination. The bio1 mutant of Arabidopsis described in this report clearly demonstrates that some auxotrophs in higher plants are eliminated through embryonic lethality. Further analysis of this mutant should provide valuable information on the nature of plant auxotrophs, the biosynthesis and utilization of biotin in plants, and the underlying causes of developmental arrest in lethal mutants of Arabidopsis. PMID- 2909402 TI - Timing in the regulation of neural crest cell migration: retarded "maturation" of regional extracellular matrix inhibits pigment cell migration in embryos of the white axolotl mutant. AB - In larvae of the white axolotl mutant (Ambystoma mexicanum), contrary to normal dark ones, trunk pigmentation is restricted because the epidermis is unable to support subepidermal migration of pigment cells from the neural crest (NC). This study examines whether the subepidermal extracellular matrix (ECM) is the defective component which prevents pigment cell migration in the white embryo. We transplanted subepidermal ECM, adsorbed in vivo on membrane microcarriers, from and to white and dark embryos in various combinations. White embryos have demonstrated normal NC cell migration along the medioventral pathway, and in order to test the effects of medial ECM on subepidermal migration, this ECM was similarly transplanted. Carriers with ECM attached were inserted subepidermally in host embryos at a premigratory NC stage. Control carriers without ECM and carriers with subepidermal ECM from white donors did not affect NC cell migration in white or dark embryos. In contrast, subepidermal ECM from dark donors triggered NC cell migration in the subepidermal space of both white and dark hosts. Remarkably, subepidermal ECM from white donors which were older than those normally used also stimulated migration in embryos of both strains. Likewise, medial ECM from white donors elicited migration in white as well as dark hosts. Pigment cells occurred among those NC cells that were stimulated to migrate in response to contact with ECM on carriers. These results indicate that the subepidermal ECM of the white embryo is transiently defective as a substrate for pigment cell migration, implying that "maturation" of the ECM is retarded beyond the times during which pigment cells are able to respond. In contrast, the medial ECM of the white embryo appears to mature normally. These findings suggest that the effect of the d gene is expressed regionally through the subepidermal ECM during a limited period of development. Hence, the action of the d gene seems to retard ECM maturation, bringing it out of phase with the migratory capability of the pigment cells. We propose that such a shift in relative timing of the developmental phenomena involved inhibits pigment cell migration in embryos of the white axolotl mutant and, accordingly, that the restricted pigmentation of the mutant larva is generated through heterochrony. PMID- 2909403 TI - Animal and vegetal teloplasms mix in the early embryo of the leech, Helobdella triserialis. AB - In embryos of the glossiphoniid leech, Helobdella triserialis, as in many annelids, cytoplasmic reorganization prior to first cleavage generates distinct animal and vegetal domains of yolk-deficient cytoplasm, called teloplasm. Both domains are sequestered to the D' macromere, progenitor of the definitive segmental tissues, during the first three rounds of cell division. And it has been believed that during the fourth round of cell division, the obliquely equatorial cleavage of macromere D' cleanly segregates animal teloplasm into an ectodermal precursor, cell DNOPQ, and vegetal teloplasm into a mesodermal precursor, cell DM. But here we report a hitherto unobserved cytoplasmic rearrangement between the second and the fourth divisions that seems to mix the animal and vegetal domains of teloplasm. The newly observed rearrangement consists of the movement of vegetal teloplasm toward the animal pole of cell D' between the second and the fourth cell divisions. Animal and vegetal teloplasms form a single pool of teloplasm in cell D' which is then divided between DM and DNOPQ at the fourth division. The movement of teloplasm was inferred by examination of embryos fixed and sectioned between the second and the fourth rounds of cleavage and was confirmed in living embryos microinjected with rhodamine 123, a fluorescent mitochondrial stain. PMID- 2909404 TI - The role of lateral migration in the formation of acetylcholine receptor clusters induced by basic polypeptide-coated latex beads. AB - During the formation of the neuromuscular junction, the nerve induces the clustering of acetylcholine receptors (AChR) in the postsynaptic membrane. This process can be mimicked by treating cultured Xenopus myotomal muscle cells with basic polypeptide-coated latex beads. Using this bead-muscle coculture system, we examined the role of lateral migration of AChRs in the formation of the clusters. First, we studied the contributions of the preexisting and newly inserted AChRs. After the cluster formation was triggered by the addition of the beads, preexisting receptors were immediately recruited to the bead-muscle contacts and they remained to be the dominant contributor during the first 24 hr. New AChRs, which were inserted after the addition of the beads, appeared at the clusters after a 4-hr delay and, thereafter, there was a steady increase in their contribution. After 24-48 hr, newly inserted AChRs could be detected at the bead induced clusters to the same extent as the preexisting AChRs. During this period, new receptors were continuously inserted into the plasma membrane, but there was no evidence of a local insertion at sites of new cluster formation. Concanavalin A (Con A) at a concentration of 100 micrograms/ml caused a fivefold decrease in the fraction of mobile AChRs and a large decrease in their diffusion coefficient. Pretreatment of cells with Con A suppressed clustering of preexisting AChRs, but left intact the contribution of the mobile newly inserted AChRs. Succinyl Con A, the divalent derivative of Con A which affected the mobility to a much less extent than Con A, had little effect on the clustering process. These results show that the formation of AChR clusters in Xenopus is mediated by lateral migration of AChRs within the plasma membrane and are consistent with the diffusion-trap hypothesis, which depicts freely diffusing AChR aggregating at the bead-muscle contacts where they bind to other localized molecular specializations induced by the beads. PMID- 2909405 TI - Cell lineage patterns in the shoot meristem of the sunflower embryo in the dry seed. AB - We mapped the fate of cells in the shoot meristem of the dry-seed embryo of sunflower, Helianthus annuus L. cv. Peredovic, using irradiation-induced somatic sectors. We analyzed 249 chlorophyll-deficient or glabrous (hairless) sectors generated in 236 plants. Most sectors observed in the inflorescence extended into vegetative nodes. Thus cell lineages that ultimately gave rise to reproductive structures also contributed to vegetative structures. No single sector extended the entire length of the shoot. Thus the shoot is not derived from one or a few apical initials. Rather, the position, vertical extent, and width of the sectors at different levels of the shoot suggest that the shoot is derived from three to four circumferential populations of cells in each of three cell layers of the embryo meristem. Sectors had no common boundaries even in plants with two or three independent sectors, but varied in extent and overlapped along the length of the shoot. Thus individual cells in a single circumferential population behaved independently to contribute lineages of different vertical extents to the growing shoot. The predicted number of circumferential populations of cells as well as the apparent cell number in each population was consistent with the actual number of cells in the embryo meristem observed in histological sections. PMID- 2909406 TI - Cloning of Tetrahymena genomic sequences whose message abundance is increased during conjugation. AB - A molecular and biochemical inquiry into protein regulation during Tetrahymena thermophila conjugation was carried out in two ways: a two-dimensional gel analysis of newly translated proteins and the molecular cloning of genes whose message abundance is increased. The two-dimensional gel analysis indicated that the synthesis of 32 predominantly basic proteins was stimulated in conjugating cells. The induction of these proteins could not be correlated with length of starvation or with mating type. The transcription pattern and molecular organization of three clones of T. thermophila genomic DNA, selected on the basis of differential hybridization to conjugating or control cell RNA, were investigated. Two of the clones, which were homologous to transcripts detected in conjugating cells, showed no rearrangements between micro- and macronuclear DNA. A third clone was divided into three segments. One segment was homologous to sequences limited to the micronucleus. A second segment hybridized to a large number of restriction fragments of micronuclear DNA digested with HindIII but to only two fragments of macronuclear DNA. A third segment, which was complementary to one transcript in conjugating cells and to two different transcripts in control cells, hybridized to two fragments in micronuclear DNA and one fragment in macronuclear DNA. PMID- 2909407 TI - Molecular analysis of a developmentally regulated gene required for Dictyostelium aggregation. AB - We have previously shown that the developmentally regulated gene D2 is induced during aggregation by pulses of cAMP, which act via the cell surface receptor and consequent signal transduction pathways (W. Rowekamp and R.A. Firtel, 1980, Dev. Biol. 79, 409-418; S.K.O. Mann and R.A. Firtel, 1987, Mol. Cell. Biol. 7, 458 469; S.K.O. Mann, C. Pinko, and R.A. Firtel, 1988, Dev. Biol., in press). In this manuscript, we compare the complete derived amino acid sequence for D2 to two cloned and sequenced eukaryotic esterases and examine the requirement of the D2 gene product for development. Amino acid sequence data comparisons suggest that D2 encodes a serine esterase with strong sequence identity to Torpedo acetylcholine esterase and a Drosophila esterase. The protein has a putative leader sequence, suggesting that it is shunted into vesicles. Using an antisense gene construct driven by a Discoidin I promoter, whose transcriptional activity depends on the growth conditions of the cells, we show that inhibition of D2 mRNA accumulation results in an abnormal developmental program that includes the absence of normal streaming and incomplete aggregate formation and subsequent development. We suggest that D2 encodes an esterase function required for proper aggregation and subsequent development. PMID- 2909408 TI - Evans blue treatment promotes blastomere separation and twinning in Lytechinus pictus embryos. AB - Demembraned Lytechinus pictus embryos briefly treated with the dye Evans Blue during the first cleavage division subsequently showed frequent blastomere disengagement leading to development of twinned embryos. Further development of twinned embryos was observed in hanging drops and in batch cultures. The timing of micromere production was disturbed in some twinned embryos, but this disturbance was not correlated with subsequent developmental problems. Many twinned embryos resulting from blastomere separation following Evans Blue treatment developed into small but normal-appearing plutei. PMID- 2909409 TI - Clonal origins of cells in the pigmented retina of the zebrafish eye. AB - Mosaic analysis has been used to study the clonal basis of the development of the pigmented retina of the zebrafish, Brachydanio rerio. Zebrafish embryos heterozygous for a recessive mutation at the gol-1 locus were exposed to gamma irradiation at various developmental stages to create mosaic individuals consisting of wild-type pigmented cells and a clone of pigmentless (golden) cells in the eye. The contribution of individual embryonic cells to the pigmented retina was measured and the total number of cells in the embryo that contributed descendants to this tissue was determined. Until the 32-cell stage, almost every blastomere has some descendants that participate in the formation of the pigmented retina of the zebrafish. During subsequent cell divisions, up to the several thousand-cell stage, the number of ancestral cells is constant: approximately 40 cells are present that will give rise to progeny in the pigmented retina. Analysis of the size of clones in the pigmented retina indicates that the cells of this tissue do not arise through a rigid series of cell divisions originating in the early embryo. The findings that each cleavage stage cell contributes to the pigmented retina and yet the contribution of such cells is highly variable are consistent with the interpretation that clonal descendants of different blastomeres normally intermix extensively prior to formation of the pigmented retina. PMID- 2909410 TI - Development of the enteric nervous system in the moth. I. Diversity of cell types and the embryonic expression of FMRFamide-related neuropeptides. AB - The enteric nervous system (ENS) of the larval moth Manduca sexta consists of two small ganglia and several nerve networks that lie superficially along the alimentary tract. Within this system are approximately 600 neurons that exhibit a spectrum of biochemical and morphological characteristics and that express these features in a definable sequence during development. The accessibility of both the neural and nonneural components of the moth ENS throughout embryogenesis makes it a potentially useful model in which to examine the developmental regulation of transmitter phenotype. In this paper, we have focused on the differentiation of the enteric plexus (EP) cells, a heterogeneous population of enteric neurons that are distributed across the foregut-midgut boundary. Unlike many neurons of the CNS in insects, the cells of the enteric plexus are not uniquely identifiable. While the total number of EP cells is constant, their locations vary significantly from animal to animal. However, several distinct classes of neurons can be identified within this population on the basis of morphology and transmitter phenotype, including one class that contains substances related to the molluscan peptide Phe-Met-Arg-Phe-amide (FMRFamide). Expression of this FMRFamide-like material within the enteric plexus is position specific, occurring only in neurons on the midgut and not in those on the foregut. FMRFamide-like immunoreactivity first appears in approximately one-third of these cells at 65% of development; this pattern is retained without apparent modification throughout subsequent embryonic and postembryonic development. In the following paper, we describe the sequence of stereotyped cell migration that precedes the expression of this peptidergic phenotype and that underlies the formation of the enteric plexus during embryogenesis. PMID- 2909411 TI - Development of the enteric nervous system in the moth. II. Stereotyped cell migration precedes the differentiation of embryonic neurons. AB - The enteric plexus is a discrete portion of the enteric nervous system (ENS) in the larval moth Manduca sexta. It consists of a stereotyped array of nerves extending across specific regions of both the foregut and midgut. Within these nerves are approximately 400 neurons (the EP cells), which do not appear to be uniquely identifiable but exhibit a spectrum of morphological and biochemical phenotypes. In this report we have described the morphogenetic events by which the enteric plexus is created during embryogenesis and have characterized the morphological differentiation of the EP neurons. In particular, we have demonstrated a prominent role for stereotyped cellular migration in the formation of this region of the ENS. The neurons of the enteric plexus arise from the dorsal epithelium of the foregut in the form of a dense, triangular packet. Between 40 and 65% of embryogenesis, the cells of this packet become progressively dispersed by a sequence of migratory events: an initial, slow phase of migration that is circumferentially directed around the foregut, and a rapid, dispersing phase by which the EP cells achieve their mature distributions across the foregut and midgut surface. These migratory phases occur along defined pathways on the gut and result in cellular translocations of up to 250 microns. In the early phase, some migrating neurons extend long axons in stereotyped directions, while others retain a simple bipolar morphology. Neurons of both morphological types are interspersed throughout the initial packet of cells and participate equally in the migratory process. Toward the end of migration, cells with the simpler morphology also extend axons along predictable pathways. Several additional subtypes subsequently differentiate in various regions within the plexus. The expression of specific peptidergic substances (related to the molluscan peptide Phe-Met-Arg-Phe-NH2, as described in the accompanying paper (P. F. Copenhaver and P. H. Taghert, 1988, Dev. Biol. 130, 70-84) commences within the EP cell population only after these migratory phases are complete and can be correlated with the outcome of cellular migration: only neurons that navigate onto the midgut regions of the plexus subsequently exhibit the peptidergic phenotype. This system should provide an excellent model with which to examine the mechanisms underlying the migratory process and the potential roles of cellular migration in regulating neuronal differentiation. PMID- 2909412 TI - Vasopressin in rats with genetic and streptozocin-induced diabetes. AB - Rats were administered streptozocin (STZ; 50 or 75 mg/kg i.v., tail vein) or vehicle. Approximately 2 wk later, venous and arterial catheters was implanted for subsequent (24 h later) vasopressin, electrolyte, and hemodynamic measurements. STZ-induced diabetic (STZ-D) rats demonstrated a dose-dependent increase in the plasma glucose concentration, plasma osmolality, and plasma vasopressin concentration. Mean arterial blood pressure (MABP) was unchanged, but heart rate was reduced. Diabetes-prone BB rats, maintained on or withdrawn from insulin treatment for 24-48 h, and diabetes-resistant rats were instrumented and studied as above. Spontaneous-diabetes-prone rats demonstrated increase in plasma glucose concentration and plasma osmolality similar to STZ-D rats but had significantly greater plasma vasopressin concentrations. The significant decrease in MABP observed in these animals probably contributed to the enhanced vasopressin response. We conclude that both osmotic and cardiovascular parameters play important roles in vasopressin secretion in diabetic rats. PMID- 2909413 TI - Regulation of carnitine palmitoyltransferase synthesis in spontaneously diabetic BB Wistar rats. AB - The long-term regulation of hepatic mitochondrial carnitine palmitoyltransferase (CPT) was studied in control, insulin-treated, and untreated spontaneously diabetic BB Wistar rats. The activity of CPT was elevated approximately twofold in the untreated diabetic rats. This corresponded to an approximately equivalent elevation in the immunoreactive CPT activity. mRNACPT was assayed by reticulocyte lysate translation and by dot blot to a CPT oligonucleotide probe. The level of mRNACPT was approximately proportional to the observed CPT activity. A cDNA probe to CPT was developed, and transcriptional activity for CPT was assessed in isolated hepatic nuclei. Again, transcription of CPT mRNA was approximately proportional to the observed activity. We therefore conclude that at least part of the long-term regulation of hepatic CPT in spontaneously diabetic BB Wistar rats is the product of increased de novo synthesis of CPT protein brought about by regulation at the transcriptional level. Additional control of the amount of CPT may be via the regulation of RNA processing and turnover and enzyme insertion into the mitochondrial membrane. PMID- 2909414 TI - Evidence for multifactorial origin of diabetes-induced embryopathies. AB - Serum factors characteristically altered in the diabetic state, e.g., glucose, ketone bodies (beta-hydroxybutyrate), and somatomedin inhibitors, induce dysmorphogenesis with or without growth retardation in rodent embryos in whole embryo culture. Furthermore, serum from diabetic animals, which contains combinations of altered factors, is teratogenic, thereby implying that the diabetic embryopathy is of a multifactorial origin. However, a detailed investigation with various combinations of factors at known concentrations to test this hypothesis has not been conducted. Therefore, we employed combinations of hyperglycemia (300 and 600 mg/dl; 16.6 and 33.3 mM), hyperketonemia (8 and 16 mM D-beta-hydroxybutyrate), and an 800- to 1000-Mr somatomedin-inhibitor serum fraction (at an amount equal to that found in 0.05 and 0.1 ml of serum from a diabetic rat per deciliter culture medium), which represented doses with low teratogenic potential, to determine if interactions of the factors could occur that would increase the risk of malformations in mouse embryos exposed in whole embryo culture during gastrulation and neurulation. The results demonstrate that glucose and D-beta-hydroxybutyrate can act synergistically to produce growth retardation and additively to induce malformations. The addition of the somatomedin inhibitor exacerbates the induction of malformations produced by the ketone body and glucose. Thus, the origin of the diabetic embryopathy may be multifactorial, involving several altered maternal factors. PMID- 2909415 TI - Kidney hemodynamics after ketone body and amino acid infusion in normal and IDDM subjects. AB - Little information is available on the hemodynamic response (renal reserve) of the diabetic kidney during an acute amino acid infusion, which has been shown to increase glomerular filtration rate (GFR) in normal humans. We recently found that the infusion of ketone bodies is able to raise GFR in both normal subjects and insulin-dependent diabetes mellitus (IDDM) patients. The aim of this study was to evaluate the renal reserve in 15 IDDM patients with a duration of diabetes of greater than 9 yr [8 with albumin excretion rate less than 15 micrograms/min (group 1) and 7 with albumin excretion rate greater than 100 micrograms/min (group 2)] and in 8 normal subjects during amino acid infusion (33 mumol.kg-1.min 1, Travasol 10% wt/vol solution containing 0.154 mM sodium chloride concentration; Travenol, Savage, MD) and during acetoacetic sodium salt (25 mumol.kg-1.min-1) infusion. Blood glucose was clamped at euglycemic levels. The infusion of sodium acetoacetate resulted in a 10- to 15-fold increase in circulating concentrations of ketone bodies, which were similar in magnitude in normal subjects and diabetic patients. The GFR peak increase above baseline after sodium acetoacetate infusion was 28% in normal subjects and 27% in group 1 and 19% in group 2 diabetic patients. The infusion of amino acid solution produced a three- to fivefold increase in plasma concentrations of amino acids in both normal subjects and diabetic patients. The GFR peak increase above baseline after amino acid infusion was significantly lower in diabetic patients (IDDM group 1: 5%, P less than .01; IDDM group 2: 6%, P less than .01) than in normal subjects (38%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2909416 TI - Influence of gender and menopause on gastric emptying and motility. AB - The aims of this study were to determine (a) if there are differences in gastric emptying rates of a mixed liquid and solid meal between men and women, (b) if menopausal status affects gastric emptying, and (c) whether differences in solid emptying rates are associated with alterations in postprandial antral motility parameters. A dual-isotope technique was used to measure gastric emptying in 20 men, 18 premenopausal women, 14 postmenopausal women, and 8 postmenopausal women taking estrogen and progesterone hormone replacement. A multilumen perfusion catheter was used to measure antral motility in 6 men and 6 premenopausal women. Premenopausal women, postmenopausal women, and postmenopausal women taking oral estrogen and progesterone had slower gastric emptying of liquids than did men (p less than 0.025, less than 0.05, and less than 0.025, respectively). Both premenopausal women and postmenopausal women taking sex hormone replacement therapy had slower emptying of solids than did men (p less than 0.025 and less than 0.05) but, in contrast to liquids, postmenopausal women not on hormone replacement emptied solids at a rate similar to that of men. There were no differences in postprandial antral motility parameters between men and premenopausal women. These findings support the hypothesis that sex steroid hormones have variable inhibitory effects on gastric emptying of a mixed meal and this should be considered when studying gastric emptying in disorders that occur predominantly in premenopausal women. PMID- 2909417 TI - Abnormal postcibal antral and small bowel motility due to neuropathy or myopathy in systemic sclerosis. AB - Two hypotheses were tested: first, the postcibal motility disorders occur in both the antrum and small bowel of systemic sclerosis patients with gastrointestinal symptoms; second, that dysmotility may result from a neuropathic stage in this disease. Upper gut perfusion manometry (3 h fasting, 2 h fed) was performed and compared with data from similarly studied healthy laboratory controls (n = 15). Only 1 of 8 scleroderma patients had an interdigestive motor complex during the 3 h fasting period [0.1 +/- 0.1 (SEM) for systemic sclerosis vs. 1.4 +/- 0.16 (SEM) for controls, p less than 0.05]; 2 other patients had fasting duodenal incoordinated bursts of phasic pressure activity in the duodenum or proximal jejunum. Distal antral motility index [MI = In (sum of amplitude x number of contractions + 1)] was lower (12.4 +/- 0.5, p less than 0.01) than that in controls (14.4 +/- 0.14); both the amplitude and frequency of antral pressure activity were lower (p less than 0.05) in systemic sclerosis. The intestinal fed pattern was characterized by reduced amplitude and frequency of contractions in 6 patients; 2 patients had excessive phasic or tonic small bowel pressure activity, or both. Thus, antral hypomotility is present in most symptomatic scleroderma patients; proximal small bowel postcibal motility is characteristically reduced; a minority of such patients have incoordianted fasting or postcibal hypermotility suggestive of a neuropathy. Manometry identifies the type and region of dysmotility in systemic sclerosis; our results suggest that there are neuropathic and myopathic stages of the upper gut involvement in systemic sclerosis. PMID- 2909418 TI - Role of muscarinic receptor subtypes in the regulation of migrating myoelectric complex in the dog. AB - The role played by muscarinic receptor subtypes in the regulation of the migrating myoelectric complex was investigated in 7 dogs chronically implanted with bipolar electrodes along the small intestine. Pirenzepine (3-300 micrograms/kg i.v.) and atropine (1-30 micrograms/kg i.v.) were used as selective and unselective antagonist, respectively. Atropine (30 micrograms/kg) significantly delayed the onset of the next complex. On the contrary, pirenzepine displayed a biphasic action: low doses (less than 100 micrograms/kg) shortened the cycle period, whereas at 300 micrograms/kg the drug behaved like atropine. Pirenzepine affected the cycle period in the low-dose range by reducing the length of phase I. Both atropine and pirenzepine impaired the migration of the ongoing complex, and significantly reduced the migration velocity of the following one. These findings suggest that the initiation of the migrating myoelectric complex in the dog is under an inhibitory influence mediated by the M1 muscarinic receptor subtype; on the other hand, M2 receptor activation is needed for the onset of the activity front. Finally, both receptor subtypes determine the normal migration of phase III. PMID- 2909419 TI - 7-Methyl bile acids: effects of chenodeoxycholic acid, cholic acid, and their 7 beta-methyl analogues on the formation of cholesterol gallstones in the prairie dog. AB - The purpose of this study was to compare the effects of the naturally occurring bile acids (chenodeoxycholic acid and cholic acid) with their 7-methyl analogues (3 alpha,7 alpha-dihydroxy-7 beta-methyl-5 beta-cholanoic acid and 3 alpha,7 alpha,12 alpha-trihydroxy-7 beta-methyl-5 beta-cholanoic acid) on gallstone formation and prevention and cholesterol metabolism in the prairie dog. Sixty animals were fed a semipurified diet, containing 0.4% cholesterol, with one of the following acids (0.1%): chenodeoxycholic, cholic, 3 alpha,7 alpha-dihydroxy-7 beta-methyl-5 beta-cholanoic, or 3 alpha,7 alpha,12 alpha-trihydroxy-7 beta methyl-5 beta-cholanoic acid. This concentration of dietary bile acids amounts to a dose of 27-30 mg/kg.day. After 8 wk, 89% of control animals had gallstones and 94% had cholesterol crystals. Chenodeoxycholic and 3 alpha,7 alpha-dihydroxy-7 beta-methyl-5 beta-cholanoic acids decreased the incidence of gallstones to 50%. Cholic acid and 3 alpha,7 alpha,12 alpha-tri-hydroxy-7 beta-methyl-5 beta cholanoic acid did not prevent gallstone formation. The liver cholesterol level was decreased by chenodeoxycholic acid, whereas cholic and 3 alpha,7 alpha,12 alpha-trihydroxy-7 beta-methyl-5 beta-cholanoic acids increased serum and liver cholesterol. Each administered bile acid became the predominant biliary bile acid and 7-methyl analogues did not increase secondary bile acids. Fecal analysis of radioactive metabolites using 14C-labeled 7-methyl analogues showed that these compounds are resistant to bacterial 7-dehydroxylation. It was concluded that 3 alpha,7 alpha-dihydroxy-7 beta-methyl-5 beta-cholanoic acid inhibited gallstone formation as effectively as chenodeoxycholic acid, whereas both cholic and 3 alpha,7 alpha,12 alpha-trihydroxy-7 beta-methyl-5 beta-cholanoic acids were not effective. The effects of 7-methyl analogues on the parameters of cholesterol metabolism that we studied were similar to those of their parent compounds, chenodeoxycholic and cholic acids. Thus, 3 alpha,7 alpha-dihydroxy-7 beta-methyl 5 beta-cholanoic acid but not 3 alpha,7 alpha,12 alpha-trihydroxy-7 beta-methyl-5 beta-cholanoic acid offers promise in cholelitholytic therapy for the prevention and possibly dissolution of cholesterol gallstones. PMID- 2909420 TI - Effect of FOY-305 (camostate) on severe acute pancreatitis in two experimental animal models. AB - Two models of severe acute pancreatitis were chosen and pancreatitis induced by sodium taurocholate and by a choline-deficient ethionine-supplemented diet, to evaluate the effectiveness of FOY-305 (camostate), a new synthetic trypsin inhibitor. Prophylactic administration of FOY-305 had a significantly favorable effect on the course of the sodium taurocholate-induced disease and on the survival rate of the treated group. A beneficial effect on the amylase and lipase content in serum and ascites was found, but no effect was observed on enzyme concentration in pancreatic tissue or on the degree of histologically detectable organ destruction. Therapeutic administration of FOY-305 had a significantly positive influence when infused directly, 5 and 30 min after the operation, whereas enzyme increase and organ destruction remained unaffected. FOY-305 showed a beneficial effect when given prophylactically or therapeutically at the beginning of the pancreatitis induced by a CDE diet, with no significant change in enzyme increase and degree of organ destruction. The favorable effect on survival time and rate in the early phase of these two severe experimental forms of pancreatitis may justify an evaluation of FOY-305 in a clinically controlled study. PMID- 2909421 TI - Role of the pancreas in the control of interdigestive gastrointestinal motility. AB - Our aim was to determine if the pancreas regulates the interdigestive motor patterns of the upper gut. Four dogs were prepared with gastric and intestinal manometry catheters and interdigestive (fasting) motility was measured before and after total surgical pancreatectomy. The characteristics of the gastric and intestinal migrating motor complex were very similar before and after pancreatectomy. The time intervals between successive migrating motor complexes in the antrum (145 +/- 11 vs. 135 +/- 15 min, mean +/- SE) or small intestine (133 + 10 vs. 137 +/- 16 min) were not significantly (p greater than 0.4) altered by pancreatectomy, but the antral motility index (the sum of the antral contractions in a 15-min period) was greater after pancreatectomy (53 +/- 6 vs. 27 +/- 4; p less than 0.05). Pancreatectomy led to undetectable plasma concentrations of pancreatic polypeptide, but had no effect on absolute concentrations of plasma motilin or on the cycling of plasma motilin in association with the duodenal migrating motor complex. We conclude that the pancreas and pancreatic polypeptide play little, if any, role in controlling canine interdigestive motility of the upper gut. PMID- 2909422 TI - Infarction of intestine with massive amyloid deposition in two patients on long term hemodialysis. AB - Two patients undergoing hemodialysis for 19 and 13 yr, respectively, developed intestinal infarction with extensive amyloid deposits in the muscle layer and blood vessels. In 1 patient the deposit reacted positively with antiserum to beta 2-microglobulin by immunohistochemical stain, and therefore was classified as beta 2-microglobulin in origin. The amyloid protein of the other patient remains unclassified. In patients with gastrointestinal symptoms who have been undergoing hemodialysis for long periods of time, amyloidosis of the intestine should be considered. PMID- 2909423 TI - Pancreatic pseudocyst as a cause for secondary achalasia. AB - Secondary achalasia is commonly due to cancer. Benign causes are rare and an association with pancreatitis has never been made. Our patient presented with clinical, manometric, endoscopic, and radiographic features of achalasia that occurred in conjunction with a pancreatic pseudocyst extending into the mediastinum. Documentation of this unique relationship was made on two occasions after episodes of complicated pancreatitis and was confirmed by restoration of normal esophageal function after drainage of the pseudocyst. Onset of dysphagia occurring in association with pancreatitis suggests the presence of a pseudocyst and secondary achalasia. PMID- 2909424 TI - Fatal hemorrhage from an arterio-portal-peritoneal fistula after percutaneous liver biopsy. AB - Exsanguinating hemorrhage complicated a percutaneous needle biopsy in a 64-yr-old woman with a probable collagen vascular disease. Angiography performed before Gelfoam embolization demonstrated a hepatic arterio-portal venous-peritoneal fistula, a lesion not previously described, to be a cause of the hemorrhage. Although surgery remains the treatment of choice, the role of selective hepatic arteriography and Gelfoam embolization in patients with serious hemorrhage who are poor surgical risks needs evaluation. PMID- 2909425 TI - The polyalbumin hypothesis: where is it in 1989? PMID- 2909426 TI - Extracorporeal shock-wave lithotripsy of common bile duct stones. PMID- 2909427 TI - Three cases of gastric spirochetelike organisms. PMID- 2909428 TI - Galactose clearance and hepatic blood flow. PMID- 2909429 TI - Breath hydrogen in celiac disease. PMID- 2909430 TI - Vagal branches for gastric acid secretion. PMID- 2909431 TI - Aspirin and colonic epithelium. PMID- 2909432 TI - Diagnostic value of esophageal balloon distention. PMID- 2909433 TI - [14C]D-xylose breath test for small intestinal bacterial overgrowth. PMID- 2909434 TI - Overflow theory of ascites formation. PMID- 2909435 TI - Chest pain and inability to belch. PMID- 2909436 TI - Phosphate transport in human jejunal brush-border membrane vesicles. AB - Phosphate transport was studied in isolated brush-border membrane vesicles prepared from human jejunum. Transport consisted of two components: passive diffusion across the brush border, and sodium-dependent, carrier-mediated uptake. Both carrier-mediated transport and passive diffusion of phosphate were significantly greater at pH 6.1 than at pH 7.4. Sodium-dependent uptake was saturable at both pH values; the apparent Km was not affected by pH, whereas Vmax was significantly greater at pH 6.1 (179.3 vs. 118.4 pM/mg per 15 s). Phosphate uptake was half-maximally stimulated by a sodium concentration of 34 mM at pH 7.4, and a sodium concentration of 76 mM at pH 6.1. At both pH values, Hill coefficients were greater than 1 and were unaffected by pH. Moreover, sodium dependent phosphate uptake was electroneutral at pH 7.4 and electrogenic at pH 6.1. These data suggest that at acid and neutral pH, both monovalent and divalent phosphate are transported across the human jejunal brush border membrane. The transport of each phosphate molecule is associated with the cotransport of two sodium ions. PMID- 2909437 TI - Splanchnic nerve activation inhibits the increase in duodenal HCO3- secretion induced by luminal acidification in the rat. AB - Acid exposure of the duodenal mucosa increased duodenal HCO3- secretion by approximately 60%. When the acid exposure was performed simultaneously with an arterial bleeding of 0.6 ml/100 g body wt (10% of the total blood volume), the increase in duodenal HCO3- secretion was totally abolished. When the acid exposure and bleeding procedures were performed at the same time in rats with bilaterally cut splanchnic nerves, alkaline secretion increased by 60%, as it did in the unbled rats. Direct electrical stimulation of the splanchnic nerves (10 Hz, supramaximal intensity) inhibited the stimulatory effect of duodenal acid exposure on alkaline secretion. Taken together, the data suggest that the sympathetic nervous system, because of splanchnic nerve activation, inhibits the acid-induced increase in duodenal HCO3- secretion. PMID- 2909438 TI - Steroid-related osteonecrosis in inflammatory bowel disease. AB - Osteonecrosis is a serious complication of steroid therapy characterized by death of all the cellular elements of bone. We describe a series of patients with steroid-induced osteonecrosis in inflammatory bowel disease. Seven of 161 patients (4.3%) treated with corticosteroids for inflammatory bowel disease over a 10-yr period developed osteonecrosis. The median age at the onset of inflammatory bowel disease was 20 yr and for osteonecrosis the median age was 28 yr. Patients had received steroids for a mean duration of 42 wk with a mean daily dose of 26 mg/day and a mean cumulative lifetime prednisone dose of 7 g. Osteonecrosis occurred within 6 mo of the last administration of steroid in all patients. It presented with joint pain in the hip or knee and was frequently mistaken for the arthralgia of steroid withdrawal or the arthropathy of inflammatory bowel disease. Multiple joints were involved in 6 of the 7 patients. Surgery for the joint disease was required in 4 of the 7 patients. The median duration of follow-up was 2 yr. Five of the 7 patients continued to have significant joint pain and disability that limited their activity. We conclude that inflammatory bowel disease predisposes to steroid-induced osteonecrosis. The age of patients is younger, and the dose and duration are considerably lower than that reported for steroid-induced osteonecrosis in other disease states. Bone scans or magnetic resonance imaging should be performed in patients with joint pain who are receiving or have recently received corticosteroid therapy. Early detection and treatment may prevent the crippling long-term complications of this disease. PMID- 2909439 TI - Hyaluronic acid and type III procollagen peptide in jejunal perfusion fluid as markers of connective tissue turnover. AB - Hyaluronic acid (hyaluronate, HA) and type III procollagen N-terminal peptide were measured in jejunal perfusion fluid in an attempt to elucidate the turnover of connective tissue components in the small bowel in health and disease. In healthy controls (n = 16) the average concentration of hyaluronic acid in jejunal perfusion fluid was 12.2 +/- 2 micrograms/L (mean +/- SEM); the mean serum concentration was 22 +/- 7 micrograms/L. The type III procollagen N-terminal peptide concentration in jejunal fluid was 0.12 +/- 0.02 micrograms/L; the mean serum concentration was 12 +/- 0.7 micrograms/L. The albumin concentration in perfusion fluid was, on average, 0.04% of the serum values. Patients with celiac disease (n = 7) and Crohn's disease (n = 10) had normal serum levels of HA and type III procollagen N-terminal peptide. The jejunal secretion rate of HA was significantly increased in both disease groups and on average about three times higher than that in controls. The secretion rate of type III procollagen N terminal peptide was not altered in celiac disease but increased more than three times in Crohn's disease. Habitual alcoholics investigated after alcohol withdrawal also had significantly increased jejunal secretion of HA but not of type III procollagen N-terminal peptide. In contrast, patients with alcoholic liver cirrhosis and similar ethanol intake had normal secretion of both substances. The findings of the study indicate that the secretion of HA into the jejunal lumen in health is considerable, possibly reflecting the rapid turnover of the intestinal mucosa. The enhanced jejunal secretion of HA in patients with celiac disease and Crohn's disease may be indicative of enhanced connective tissue response due to inflammation, but signs compatible with enhanced jejunal synthesis of type III collagen are only found in Crohn's disease. The HA secretion data in alcoholics might reflect (a) the active regeneration of the intestinal mucosa when ethanol is discontinued and (b) a possible role of the liver in this activity. PMID- 2909440 TI - Effect of iron on the guaiac reaction. AB - Most studies show that oral ingestion of iron does not cause a positive stool guaiac reaction. However, all in vitro studies show that iron does cause a positive guaiac reaction and some in vivo studies have shown a positive stool guaiac reaction in response to oral iron. This study examines this unresolved question. Twenty-five normal volunteers were given 900 mg of ferrous sulfate a day. Two Hemoccult II and two HemoQuant tests were obtained before and during iron therapy. All Hemoccult II tests were negative before and after oral iron. Four HemoQuant tests were slightly elevated before oral iron and one was slightly elevated after oral iron. Ferrous sulfate, 300 mg, was dissolved in 1 L of water. The solution was acidic (pH = 3.9) and produced a positive Hemoccult II test. When the solution was titrated with sodium hydroxide to a pH of greater than or equal to 6.0, iron precipitated out and the mixture no longer produced a positive Hemoccult II reaction. Our data show that ferric iron (Fe3+) in solution will give a positive guaiac reaction directly and ferrous iron (Fe2+) will give a positive guaiac reaction after hydrogen peroxide is added because it oxidizes Fe2+ to Fe3+. Iron solutions are acidic and when titrated toward a neutral pH, the iron is precipitated out and the solution is then guaiac-negative. Thus, our in vivo data confirm most previous in vivo studies; furthermore, the discrepancy between in vivo and in vitro studies can be explained as a pH-dependent phenomenon of in vitro iron solutions. Oral iron should not cause a positive guaiac reaction, and the HemoQuant results show no increase in occult blood loss in subjects on oral iron therapy. PMID- 2909441 TI - Natural history and epidemiologic studies of peptic ulcer disease in Japan. AB - Japanese research on the natural history and epidemiology of peptic ulcer disease is presented. Descriptive summaries from several national and regional studies provide information that may be useful for comparison with corresponding information from Western nations. PMID- 2909442 TI - Toward an epidemiology of gastropathy associated with nonsteroidal antiinflammatory drug use. AB - The thesis of this paper is that gastropathy associated with nonsteroidal antiinflammatory drugs (NSAIDs) is the most frequent and, in aggregate, the most severe drug side effect in the United States. This work is based on a consecutive series of 2400 patients with rheumatoid arthritis followed prospectively for an average of 3.5 yr by ARAMIS, the American Rheumatism Association Medical Information System. We present a preliminary exploration of the magnitude of the problem, the population at risk, and the patients within that population who are at particularly high risk. Patients on NSAIDs had a hazard ratio for gastrointestinal (GI) hospitalization that was 6.45 times that of patients not on NSAIDs. Characteristically, high-risk patients for GI hospitalization and GI death are older, have had previous upper abdominal pain, have previously stopped NSAIDs for GI side effects, and have previously used antacids or H2-receptor antagonists for GI side effects. They also are frequently on corticosteroids. In contrast, patients attributing relatively minor symptoms to the drug tend to be younger and more frequently female. Our preliminary analysis is univariate and, as these variables are interdependent, firm conclusions regarding the relative importance of these risk factors will require reevaluating our data base as it is expanded using multivariate analysis. The syndrome of NSAID-associated gastropathy can be estimated to account for at least 2600 deaths and 20,000 hospitalizations each year in patients with rheumatoid arthritis alone. PMID- 2909443 TI - Tamoxifen therapy in advanced/recurrent endometrial carcinoma. AB - Forty-nine patients with advanced/recurrent endometrial carcinoma were treated with Tamoxifen, 20 mg, twice daily. There were six complete and four partial responses (response rate = 20%). The median survival of responders was 34 months compared to 6 months in nonresponders. Toxicity was minimal. PMID- 2909444 TI - Percutaneous epidural catheterization for intractable pain in terminal cancer patients. AB - We examined the effects of long-term percutaneous epidural catheterization for pain relief in nine terminally ill gynecologic cancer patients. All patients were free of side-effects such as respiratory depression, nausea, vomiting, urinary retention, or pruritus. Analgesia was excellent in six patients. Puncture-site skin inflammation occurred in four patients. Catheter dislodgement occurred in three patients. Although percutaneous epidural catheters were well tolerated in a few patients for an extended period of time, the frequency of catheter problems demonstrate that other methods such as catheter tunneling or implantable systems should be considered for long-term epidural administration of narcotics. This method appears to be most effective in patients suffering from pain due to nerve root involvement. PMID- 2909445 TI - Adenoid cystic carcinoma of the cervix in women under age 40. AB - Adenoid cystic carcinoma of the cervix, traditionally associated with a poor prognosis, occurs in postmenopausal patients in the vast majority of cases reported. Only four cases have been reported in women less than age 40, and none in women less than age 30. Three new cases of adenoid cystic carcinoma of the cervix are reported in women aged 24, 27, and 38 years. All three patients were treated with radical pelvic surgery; lymph node metastases and vascular involvement were prominent. Adjuvant chemotherapy with cisplatin was used in two patients, one of whom has had long-term survival. A review of the literature is also presented. PMID- 2909446 TI - DNA ploidy, grade, and stage in prognosis of uterine cervical cancer. AB - A retrospective study of 56 cases of uterine cervical squamous carcinoma evaluated DNA content, histological grade, and clinical stage as indicators of prognosis. Minimum survivor follow-up was 24 months. Following standard radiation therapy, there were 40 cures and 16 treatment failures. DNA content was measured by flow cytometry of pretreatment biopsies removed from paraffin. There were 18 diploid cases and 38 aneuploid (67.9%). Aneuploid cases included 6 with very high G2-M peaks (greater than or equal to 15% of the cell sample). DNA ploidy correlation with prognosis was not statistically significant. However, both grading by a multiple parameter method (P less than 0.0133) and staging (P less than 0.0064) were significant prognostic factors. Higher grade and stage correlated with treatment failure. PMID- 2909447 TI - Advanced-stage endometrial cancer: contributions of estrogen use, smoking, and other risk factors. AB - The contributions of estrogen replacement therapy, smoking, and other risk factors to the development of advanced-stage (2-4) endometrial cancer were evaluated in a case-control study of women 40-69 years old from upstate New York. Eighty-four cases and 168 matched community controls were interviewed in person about estrogen exposure and other risk factors. Despite a statistically significant increase in risk with longer use of estrogen pills (P less than 0.05), estrogen exposure actually contributed little to the overall risk of advanced-stage endometrial cancer. Other physical conditions (increased weight, lower parity, diabetes) and socioeconomic factors (education, access to medical services) largely accounted for advanced-stage disease. The evidence in this study does not support the hypothesis that women who smoke have a lower risk than nonsmokers of developing advanced-stage endometrial cancer. PMID- 2909448 TI - Cholecystectomy accompanying major abdominal surgery for gynecologic cancer. AB - In a 66-month period 950 major abdominal operations were performed for known or suspected gynecologic malignancy. Thirty-five patients (3.6%), of whom 29 had proven gynecologic malignancy, underwent cholecystectomy for cholelithiasis known from prior evaluation or found incidentally during abdominal exploration. All cholecystectomies were performed through the original incision with no direct operative morbidity or mortality. Cholecystectomy accompanying gynecologic cancer surgery appears to be well tolerated if performed expeditiously, and avoids the potential of postoperative cholecystitis in this select group of patients. PMID- 2909449 TI - Gynecologic cancer in the very elderly. AB - Due to the increasingly elderly population of the United States, it was elected to review the experience at the Cleveland Clinic Foundation in treating women older than 75 years of age for gynecologic cancer. The charts of 114 patients were reviewed to study the presentation of primary cancers, the morbidity and mortality associated with therapies, and patient survival. Cardiovascular disease, including hypertension, and diabetes mellitus were the most common associated medical problems. 36% of patients had endometrial cancer, 25% cervical cancer, 19% vulvar cancer, 12% ovarian cancer and 7% vaginal cancers. Compared to data for patients of all ages in Annual Report on the Results of Treatment in Gynecologic Cancer (Vol. 18), patients with endometrial, cervical, and vulvar cancers were of a significantly more advanced stage than expected. Therapy was modified due to patient age or medical status in 42 patients. No postoperative mortality was encountered, although patients often required multiple prolonged hospitalizations. The projected overall survival rate (Kaplan-Meier Analysis) was 44% at 5 years. It is concluded that despite their advanced age and associated medical problems, very elderly patients can usually receive definitive cancer therapies, including surgery, after careful preoperative medical evaluation and therapy. PMID- 2909450 TI - Bone metastasis from cervix cancer. AB - Among 713 patients followed after treatment for cancer of the uterine cervix, 48 (6.6%) had a metastasis to the bone. The rates of metastasis in each of the four clinical stages were 11/273 (4.0%) in stage I, 16/243 (6.6%) in stage II, 13/162 (8.0%) in stage III, and 8/35 (22.9%) in stage IV, respectively. The most frequent site of metastasis was the vertebral column, particularly the lumbar spine (23 cases, 48%) followed by the pelvic bones. Pulmonary metastasis also frequently occurred. For 32 (67%), lesions of the bone were detected within 1 year after completion of the initial treatment, and 36 (75%) died within 1 year after detection of the metastasis. Those patients who survived over 2 years were those for whom the lesions of the bone had been treated by radiotherapy followed by chemotherapy. PMID- 2909451 TI - Continuous thoracic epidural analgesia for the control of pain associated with pleural sclerosis. AB - Successful use of nonnarcotic, thoracic epidural analgesia for the control of pain associated with pleural sclerosis was accomplished in three gynecologic oncology patients with severe respiratory compromise due to malignant pleural effusions. Excellent analgesia was obtained with no observed anesthetic complications. PMID- 2909452 TI - Uterine leiomyosarcoma--magnetic resonance imaging. AB - Magnetic resonance (MR) scanning shows great promise as an imaging tool to evaluate the pelvis as a result of contrast resolution and lack of ionizing radiation. For these reasons, it is assuming an important role in staging gynecologic neoplasms, and evaluating diseases in the gravid pelvis. A case of uterine leiomyosarcoma is presented in which MR imaging was able to delineate the extent and tissue characteristics of the lesion more precisely than CT scan. PMID- 2909453 TI - Adenocarcinoma of the endometrium and endometrioid carcinoma of the ovary associated with pregnancy. AB - Nine well-accepted cases of endometrial carcinoma associated with pregnancy have been reported. A 10th patient is added and the cases are briefly summarized. At the time of her definitive surgery 6 weeks postpartum, our patient was also found to have a Stage I endometrioid ovarian carcinoma. Nine of the 10 cases have been well-differentiated adenocarcinoma or adenoacanthoma and the lesions have tended to be focal with minimal or no invasion. Given the small number of patients, conclusions regarding prognosis and treatment are difficult to make. However, in younger patients with noninvasive adenocarcinoma of the endometrium, the adnexa may be spared. Endometrioid adenocarcinoma of the ovary, discovered incidentally in our patient, is associated with a concomitant adenocarcinoma of the endometrium in 5-29% of cases, but the present case in which the lesions coexisted with pregnancy appears to be the first such report in the literature. PMID- 2909454 TI - Stage II papillary clear cell adenocarcinoma of the vagina during observation in a diethylstilbestrol-exposed daughter. AB - Although many cases of Diethylstilbestrol (DES)-associated clear cell adenocarcinoma (CCA) of the cervix and vagina have occurred, few have arisen in patients whose initial gynecologic evaluation has revealed only nonmalignant DES related changes. We report a case of a 32-year-old lady who developed a stage II CCA after 8 years of thorough gynecologic examinations. This case substantiates the need for long-term gynecologic assessment in DES daughters. PMID- 2909455 TI - Urethral placement through a bilateral myocutaneous gracilis flap neovagina. AB - Malignant melanoma of the vagina is an uncommon genital tumor. When the lesion arises in the distal vagina, radical surgery has been the only treatment to produce long-term survivors. A total vaginectomy, vulvectomy, and bilateral groin node dissection is recommended to assure adequate margins. Sexual function is lost unless reconstruction is performed. The bilateral myocutaneous gracilis flap neovagina has been a successful plastic procedure after exenterative procedures that result in loss of bladder and/or rectum. The authors present a technique in which bladder function was preserved after creation of a gracilis flap neovagina in a patient with Stage I melanoma of the distal vagina. Placement of the distal urethra through the reconstructed gracilis flap neovagina resulted in preservation of urinary function and continence, primary closure of the vulvar defect, and satisfactory sexual function. Two and one-half years after surgery the patient has good bladder and vaginal function without significant sequel. PMID- 2909456 TI - Management of localized non-Hodgkin's lymphoma: the experience at St. Bartholomew's Hospital 1972-1985. AB - A retrospective study of 202 patients with clinical stage I and II non-Hodgkin's lymphoma managed at St. Bartholomew's Hospital between 1972 and 1985 was conducted. Patients were treated either with radiotherapy alone, radiotherapy and adjuvant chemotherapy, or chemotherapy (with or without adjuvant radiotherapy). At the onset of the study it was intended that all patients with localized NHL should be treated with involved field radiotherapy and adjuvant 'CVP'. As it became apparent that this was inadequate for some patients and too toxic for others a flexible approach was later adopted. Treatment selection depended on age, volume, distribution of disease and histological subtype. The actuarial 5 year overall survival for the whole group was 70 per cent. Death from lymphoma after 5 years was very rare. Increasing age and high grade histology were highly significant adverse prognostic factors by multivariate analysis. The results for patients with high grade and low grade histology were therefore analysed separately, as was the outcome for patients presenting with either gastrointestinal or skin lymphomas. During the latter part of the study period intensive chemotherapy was given as the initial treatment to patients with high grade histology and bulky, or stage II disease. Twenty out of 24 patients so treated achieved complete remission and only one has relapsed to date. These results are encouraging and probably explain the absence of a difference in prognosis between patients with stage I and IE disease and those with stage II and IIE disease observed over the whole period of the study. Remission was achieved in the overwhelming majority of patients with low grade histology for whom radiotherapy was selected as primary therapy. Duration of remission was better in patients who received adjuvant chemotherapy than in those treated with radiation alone, but no difference in overall survival was observed between these groups. Neither stage nor the presence of a follicular histological pattern correlated with prolonged survival in patients with low grade histology. PMID- 2909457 TI - Lymphoplasmacytoid and small cell centrocytic non-Hodgkin's lymphoma--a retrospective analysis from St Bartholomew's Hospital 1972-1986. AB - Lymphoplasmacytoid (lpc) and small cell centrocytic (scc) lymphoma are the two major sub-types of diffuse low grade non-Hodgkin's Lymphoma (NHL) within the Kiel classification. The presentation features and outcome for all 112 patients with these diagnoses (60 lpc, 52 scc) managed at St Bartholomew's Hospital between 1972 and 1986 are presented. The outcome for these patients is compared with that for patients with follicular and high grade lymphomas managed at this hospital during the same period. Nineteen of the 112 patients had localized (stages I-IIE) disease. In 18 of these cases the primary site of disease was extranodal, the gastrointestinal tract being involved in 12 cases. The survival for patients with localized disease was excellent. Eighteen are currently alive with median follow up of 8 years. Ninety-three patients had advanced disease. A high incidence of splenomegaly, hepatomegaly, bone marrow and peripheral blood involvement was observed in both histological subgroups. A monoclonal paraprotein band was detected in the serum of nearly 50 per cent of patients with advanced lpc lymphoma. Patients with advanced disease were treated with either chlorambucil or cyclophosphamide, vincristine and prednisolone (CVP). The outcome was similar for both histological groups. Survival for these patients was poor (median 40 months) with less than 20 per cent surviving 5 years. Advanced age, elevated aspartate transaminase and failure to respond to treatment were identified by multivariate regression analysis as adverse prognostic factors. PMID- 2909458 TI - Treatment of acute myeloid leukemia in the elderly: a clinical dilemma. AB - Fifty-four patients representing all the cases of acute myeloid leukemia in patients aged over 60 years, presenting to three adjacent hospitals, were studied. Only 26 of the 54 patients were considered suitable for remission induction with intensive combination chemotherapy which produced seven complete remissions (CR) (26 per cent). Eighteen of the 54 patients survived longer than three months--11 of these had received remission induction chemotherapy (five CRs), two low dose cytarabine, one vincristine and vitamin A and four supportive treatment alone. By six months all the patients who had received supportive treatment had died. Patients who received intensive chemotherapy spent 77 per cent of the first 90 days in hospital and half died in hospital. Patients receiving differentiating agents or supportive care spent more time at home (37 per cent, 34 per cent of the first 90 days, respectively) but had shorter overall survival. Assessment of clinical characteristics in an attempt to predict response to treatment and survival indicated that poor performance status and the presence of infection were the most important factors. Analysis was limited by the statistically small number in the group. At present there is no reliable method of predicting which patients will respond well to treatment with intensive chemotherapy. The clinical dilemma is whether to treat more intensively to benefit a minority, or to use supportive treatment to allow more time to be spent at home albeit with a shorter overall survival. PMID- 2909460 TI - Hard choices for Bush, hard times for hospitals. PMID- 2909459 TI - Pulsed high dose oral prednisolone in relapsed or refractory multiple myeloma. AB - Seventeen unselected patients with relapsed or refractory multiple myeloma were treated with oral prednisolone 60 mg per m2 for five consecutive days with nine day treatment-free intervals. Of the fourteen patients who completed at least six courses of treatment there were five good responses (Chronic Leukemia-Myeloma Task Force Criteria), five partial responses and four failures. Median survival (all seventeen patients) was between 19 and 20 months. Eight patients achieved plateau phase (median duration 9 months). Eleven patients showed improved performance status and four became free of transfusion support. The commonest side-effect was bacterial pulmonary infection. Peptic ulceration occurred in two patients despite prophylactic ranitidine. Other steroid-related side-effects were mild and well tolerated. This study provides further evidence for the efficacy of higher dose steroid regimens in relapsed or refractory myelomatosis and confirms that durable remissions may be achieved. Responders show a gratifying improvement in quality of life and are spared the many toxicities of combination cytotoxic chemotherapy. Further studies of high dose steroid regimens in first-line therapy, especially in patients with bone marrow suppression, are clearly merited. PMID- 2909461 TI - Finances will force rationing decisions in 1989. PMID- 2909462 TI - Outpatient demand and new technology will compound money problems in 1989. PMID- 2909463 TI - Hospital groups lead quality studies in 1989. PMID- 2909464 TI - Researchers shifting focus to neurology in 1989. PMID- 2909465 TI - The diversification success story continues: survey. PMID- 2909466 TI - Community hospitals swallow pediatric losses. PMID- 2909467 TI - Fraud charges and tax challenges will mark '89. PMID- 2909468 TI - States to revisit tough issues. PMID- 2909469 TI - Research and customer satisfaction top agenda. PMID- 2909470 TI - Labor versus management: the battle of 1989. PMID- 2909471 TI - Home care's future. PMID- 2909472 TI - Data to go. PMID- 2909473 TI - Home care kids. PMID- 2909474 TI - Home work. PMID- 2909475 TI - Competition lowers cost at California hospitals. Interview by Alden Solovy. PMID- 2909476 TI - Payment, practice, and GME reform key in 1989. PMID- 2909477 TI - Get vendor promises in writing, experts advise. PMID- 2909479 TI - Purchasing, product-line strategy meet in '89. PMID- 2909478 TI - Law and money spur HMO profit status changes. PMID- 2909480 TI - State budget woes may spark a battle for bucks. PMID- 2909481 TI - How to make the transition from CFO to CEO. PMID- 2909482 TI - Home health care: new challenges, new solutions. PMID- 2909483 TI - Staphylococcus saprophyticus urease: characterization and contribution to uropathogenicity in unobstructed urinary tract infection of rats. AB - We studied the biochemical properties of the urease of Staphylococcus saprophyticus and the possible role of the urease in experimental urinary tract infections. For this purpose, the nonhemagglutinating and nonadherent strain 9325, which was isolated from a case of symptomatic urinary tract infection, was used. The urease was shown to have a Km of 6.64 mM urea and a Vmax of 4.59 mumol NH3.min-1.mg-1. The enzyme was inhibited by acetohydroxamic acid in a noncompetitive manner. By means of Sephacryl S-300 column chromatography, we determined a mean molecular weight (+/- standard error of the mean) of 420,000 +/ 16,000. To assess the contribution of S. saprophyticus urease to uropathogenicity, a urease-negative mutant was constructed by nitrosoguanidine mutagenesis. In the rat model of ascending unobstructed urinary tract infection, higher numbers of CFU.gram of tissue-1 and more-severe lesions were detected with the parent strain. Moreover, bladder stones were found in animals infected with the urease-positive strain only. Interestingly, the difference in mean bacterial counts of the bladders was found to be significant by the Wilcoxon two-sample test (P less than 0.05), whereas that between the kidney bacterial counts was not. Immunoblot studies revealed a faint antibody response in rats infected with the mutant strain, although bacteria could still be detected in the kidneys after 7 days. Sera of animals challenged with the parent strain reacted strongly with many antigens of S. saprophyticus. Our data indicate that urease is a major factor for invasiveness of S. saprophyticus, especially in the tissue of the bladder, whereas persistence in the urinary tract and nephropathogenicity of this organism are governed by factors other than urease. PMID- 2909484 TI - Immunogenicity of two formulations of oral cholera vaccine comprised of killed whole vibrios and the B subunit of cholera toxin. AB - Two formulations of oral cholera vaccine were evaluated for safety and immunogenicity in adult volunteers in Thailand, an area with sporadic cholera outbreaks. One formulation consisted of 2 x 10(11) killed vibrios and 5 mg of cholera toxin B subunit, as was previously evaluated in North American volunteers, and the other consisted of 1 x 10(11) killed vibrios and 1 mg of B subunit, as was recently evaluated in a field trial in Bangladesh. Three doses of each formulation were given with citrate-bicarbonate buffer. Neither formulation had adverse effects. The formulations stimulated similar serum immunoglobulin G (IgG) and IgA responses to Vibrio cholerae lipopolysaccharide and cholera toxin and intestinal secretory IgA responses to lipopolysaccharide and toxin after three doses. The formulation containing twice the quantity of killed vibrios stimulated better vibriocidal responses, especially to Ogawa serotype. A formulation of oral vaccine containing more killed vibrios than were included in the vaccine studied in the Bangladesh field trial may provide greater protection against cholera. PMID- 2909485 TI - Effects of divalent cations and saccharides on Vibrio metschnikovii cytolysin induced hemolysis of rabbit erythrocytes. AB - Divalent cations and polysaccharides such as inulin and dextran reversibly inhibited hemolysis of rabbit erythrocytes caused by Vibrio metschnikovii cytolysin. On the basis of the 50% inhibitory doses, the cations were divided into two groups, group I (Cd2+, Cu2+, Ni2+, Sn2+, and Zn2+) and group II (Ba2+, Ca2+, Co2+, Mg2+, Mn2+, and Sr2+). Neither divalent cations nor polysaccharides interfered with the binding of toxins to the erythrocyte membrane. Group I cations disturbed tetramer formation of cytolysin on the cytolysin-lysed erythrocyte membrane, although group II cations and dextran did not affect the process. Erythrocytes treated with cytolysin in the presence of group II cations or dextran lysed after transfer to toxin- and inhibitor (group II cations or dextran)-free buffer at both 37 and 4 degrees C. However, erythrocytes treated in the presence of group I cations lysed at 37 degrees C but not at 4 degrees C, indicating that group I cations block the temperature-dependent lesion (tetramer) forming step subsequent to the binding of cytolysin to the erythrocytes. The cytolysin-treated erythrocytes swelled in a colloid osmotic manner, and the swelling was preceded by the binding and the lesion-forming steps. It is also suggested that the lysis of the erythrocytes proceeds in a temperature independent manner and that the cytolysin does not bind to the erythrocytes at 4 degrees C. These findings suggest that the sequence of V. metschnikovii cytolysin induced hemolysis is defined by three steps: (i) a temperature-dependent binding step, (ii) a temperature-dependent lesion-forming step, and (iii) a temperature independent lysis step. PMID- 2909486 TI - Sequence homology between tetanus and botulinum toxins detected by an antipeptide antibody. AB - The extent of immunological similarity between tetanus toxin and botulinum toxins A, B, C1, and E was studied by using 10 antibodies produced against synthetic peptides representing different sequences of tetanus toxin, mouse antitetanus serum, and human Tetanus Immune Globulin. Antibodies produced against the synthetic peptides recognized tetanus toxin in an enzyme-linked immunosorbent assay and on Western blots (immunoblots) but did not appear to recognize the native protein. One of the antitetanus peptide antibodies, which was produced against a peptide from the amino terminal, cross-reacted with three of the four botulinum toxins on immunoblots. This antibody, 1, reacted strongly with botulinum toxins B and C1 and weakly with E but did not recognize type A toxin. None of the other peptide antibodies cross-reacted with the botulinum toxins. Mouse antitetanus serum and human Tetanus Immune Globulin did not recognize any of the botulinum toxins on immunoblots. The amino-terminal region of the light chain of tetanus toxin and botulinum toxin types A, B, C1, and E are known to have sequence homology. Our data demonstrate that for tetanus toxin and botulinum toxin types B, C1, and E this region also has immunological homology. Type A, which has the least amount of homology with tetanus toxin in this region, does not share this immunological homology. These data also suggest that although the native structures of tetanus and botulinum toxins have relatively few common immunological determinants, the two toxins may contain short stretches of identical or very similar amino acid sequences. PMID- 2909487 TI - Candidacidal activities of proteins partially purified from rat epidermis. AB - Proteins with approximate molecular weights of greater than 300,000 (EP greater than 300K) and 49,000 (EP 49K) were partially purified from terminally differentiated cells of 2-day-old rat epidermis. They were extracted in 0.34 M sucrose containing 0.01 M citric acid and purified by Sephacryl S-300 chromatography followed by reverse-phase column chromatography. The major constituents of EP greater than 300K and EP 49K were focused around pH 10 to 11 by sucrose gradient isoelectric focusing. Both proteins were effective at inhibiting colony formation of Candida albicans and C. tropicalis, but neither inhibited the growth of C. parapsilosis. The effect was maximum below pH 5.0 and reduced considerably above pH 5.0. The activity of EP greater than 300K on C. albicans TIMM 1623 (group A) was much stronger than that of EP 49K, whereas both proteins similarly inhibited C. albicans TIMM 1604 (group B). Their effects against C. albicans TIMM 1623 were dose dependent and were activated after a longer preincubation time, and NaCl concentration influenced their potency. At a low salt concentration and a 60-min preincubation at pH 4.5, the 50% effective dose for EP greater than 300K was calculated to be 1.7 x 10(-9) M, whereas that for EP 49K was 1.8 x 10(-7) M. PMID- 2909488 TI - Intestinal multiplication of Mycobacterium paratuberculosis in athymic nude gnotobiotic mice. AB - In this study gnotobiotic mice were inoculated with a human isolate of Mycobacterium paratuberculosis (strain Linda; ATCC 43015) in an attempt to investigate the pathogenesis of intestinal paratuberculosis. Mycobacterium paratuberculosis-monoassociated nu/+ mice developed a persistent low-level intestinal infection but did not support progressive bacillary multiplication. In contrast, monoassociated nu/nu mice eventually harbored approximately 10(7) M. paratuberculosis per g of intestinal tissue. Acid-fast bacilli and granulomas were observed in the intestinal mucosa and livers of nu/nu but not nu/+ mice. Similar results were obtained after intragastric inoculation of M. paratuberculosis into nu/+ and nu/nu flora-defined mice. These observations suggest that the presence of an intact cellular immune system is important for limiting intestinal multiplication of M. paratuberculosis. The results of this study may be relevant to our understanding of the pathogenesis of Johne's disease in ruminants and of human inflammatory bowel diseases that have a mycobacterial etiology (e.g., some cases of Crohn's disease and Mycobacterium avium Mycobacterium intracellulare enteritis in patients with acquired immunodeficiency syndrome). PMID- 2909490 TI - Determination by western blot (immunoblot) of seroconversions to toxic shock syndrome (TSS) toxin 1 and enterotoxin A, B, or C during infection with TSS- and non-TSS-associated Staphylococcus aureus. AB - Serum antibody responses to toxic shock syndrome (TSS) toxin 1 (TSST-1) and staphylococcal enterotoxins A, B, and C were determined by western blot (immunoblot) analysis of acute- and convalescent-phase paired sera from 18 TSS- and 31 non-TSS-associated Staphylococcus aureus infections. Compared with non-TSS cases, seroconversion to TSST-1 was significantly more frequent among both menstrual (5 of 8 versus 1 of 31; P less than 0.001) and nonmenstrual (3 of 10; P less than 0.05) patients. Seroconversion to staphylococcal enterotoxin A was also more frequent among both menstrual (2 of 8 versus 0 of 31; P less than 0.05) and nonmenstrual (2 of 9; P less than 0.05) TSS patients. In general, patients with TSS associated with TSST-1-positive S. aureus were more likely to seroconvert exclusively to TSST-1 (4 of 12 versus 0 of 6; P = 0.16), whereas those associated with TSST-1-negative S. aureus were more likely to seroconvert exclusively to enterotoxins (3 of 6 versus 0 of 11; P less than 0.05). Concurrent seroconversions to multiple exoproteins were more frequent among both menstrual (3 of 8; P less than 0.05) and nonmenstrual (2 of 9; P less than 0.05) TSS patients compared with persons without TSS (0 of 31). These data suggest but do not prove that enterotoxins (especially staphylococcal enterotoxin A) in addition to TSST-1 may be involved in both menstrual and nonmenstrual TSS. Furthermore, since exposure to multiple exoproteins is more likely to occur during TSS associated than non-TSS-associated S. aureus infections, the possibility of additive or synergistic effects of these putative toxins in the pathogenesis of TSS should be further explored. PMID- 2909489 TI - Biological and immunological properties of the carboxyl terminus of staphylococcal enterotoxin C1. AB - Comparisons of recently published primary sequences of staphylococcal and streptococcal pyrogenic toxins prompted an evaluation of biological and immunological properties of the C terminus of staphylococcal enterotoxin C1. The 59 N-terminal amino acids were deleted from the toxin by digestion with trypsin. The resulting fragment (Mr, 20,659) contained the remaining 180 C-terminal residues. This fragment (Trp F1) consisted of two polypeptide chains (Trp F1a and Trp F1b) linked by cysteine residues. Trp F1 was mitogenic, pyrogenic, and enhanced susceptibility of rabbits to lethal endotoxin shock. In addition, this fragment contained at least one antigenic epitope that cross-reacted with enterotoxin B. PMID- 2909491 TI - Protein 20, an immunodominant surface antigen of Eimeria bovis. AB - Autoradiography identified six 125I-labeled proteins, ranging in molecular weight (Mr) from 20,000 to approximately 110,000, on the plasmalemma of Eimeria bovis sporozoites. Immunoblotting with bovine antiserum generated by intravenous inoculations of sporozoites and with immune serum generated by per os inoculations of oocysts revealed that protein 20 (i.e., 20,000 Mr) was an immunodominant antigen on the surface of E. bovis sporozoites. PMID- 2909492 TI - Protective role of serum antibody in immunity to chlamydial genital infection. AB - Female guinea pigs were injected intraperitoneally with pooled immunoglobulin derived from animals immunized to the chlamydial agent of guinea pig inclusion conjunctivitis. Genital infections in animals receiving pooled immunoglobulin from immune animals were markedly decreased with regard to the number of inclusions detected compared with control animals. These data indicated that serum-derived antibody was able to provide a degree of protection against a chlamydial genital tract infection. PMID- 2909493 TI - Isolation of a gene encoding a Chlamydia sp. strain TWAR protein that is recognized during infection of humans. AB - Chlamydia sp. strain TWAR is a unique Chlamydia sp. that causes acute respiratory disease. A gene bank consisting of TWAR isolate AR-39 DNA in pUC19 was screened with anti-AR-39 rabbit immune sera. Two positive clones were isolated that contained 7.3-kilobase (pLC1) and 14.9-kilobase (pLC2) plasmids. Restriction mapping and hybridization studies showed that both pLC1 and pLC2 contained a common 4.2-kilobase PstI fragment. Plasmids were used as templates of in vitro transcription-translation. All three plasmids had a novel protein product of ca. 75 kilodaltons not found in the vector alone. Western blots showed that this protein reacted with anti-TWAR rabbit immune sera and with human immune serum from an individual who had proven TWAR infection. Whole-cell lysates of TWAR demonstrated a protein having the same molecular weight and immunoreactivity as the recombinant gene product. This protein was also recognized by rabbit immune serum against Chlamydia psittaci or Chlamydia trachomatis. Southern hybridizations with the cloned fragment as a probe of digests of other Chlamydia spp. showed weakly hybridizing fragments. These results suggest that we have isolated a gene encoding a protein recognized during human TWAR infection that contains some sequences shared among Chlamydia spp. PMID- 2909494 TI - Radiocesium levels measured in breast milk one year after the reactor accident at Chernobyl. AB - One hundred-two samples of colostral milk, collected during spring of 1987, approximately one year after the reactor accident at Chernobyl, were measured for radiocesium contamination. The data showed a normal-type distribution with a mean contamination concentration of 16.4 Bq L-1. A weak correlation of the data to the mothers' diet was established by taking into account four of the main staples in the area. The corresponding transfer coefficient was deduced with a value of fm = 0.06 +/- 0.03 d L-1. The resultant effective dose received by breast-feeding infants was estimated, on the average, as 0.012 mrem d-1. PMID- 2909495 TI - Estimation of indoor 222Rn from concrete. PMID- 2909496 TI - Mortality of workers at the Hanford site: 1945-1981. AB - Analyses of mortality of workers at the Hanford Site were updated to include an additional three years of data (1979-81). Deaths occurring in the state of Washington in the years 1982-85 were also evaluated. Hanford workers continued to exhibit a strong healthy worker effect with death rates substantially below those of the general U.S. population. Comparisons by level of radiation exposure within the Hanford worker population provided no evidence of a positive correlation of radiation exposure and mortality from all cancers combined or of mortality from leukemia. Estimates of cancer risk due to radiation were negative, but confidence intervals were wide, indicating that the data were consistent with no risk and with risks several times larger than estimates provided by major groups concerned with risk assessment. Of 18 categories of cancer analyzed, a correlation of borderline statistical significance was identified for female genital cancers (p = 0.05), but was interpreted as probably spurious. The previously identified correlation for multiple myeloma persisted (p = 0.002). PMID- 2909497 TI - Estimation of the mean organ doses and the effective dose equivalent from Rando phantom measurements. PMID- 2909498 TI - More on very low radiation doses. PMID- 2909499 TI - Warning from the A-bomb study about low and slow radiation exposures. PMID- 2909500 TI - Chernobyl fallout on Alpine glaciers. AB - Measurements of the gross beta activity of snow samples from four Alpine glaciers contaminated by radioactive fallout from the Chernobyl nuclear accident and a gamma-spectrum analysis of selected samples are reported. The results are discussed with respect to possible risks to the population from using meltwater from these glaciers as drinking water. PMID- 2909501 TI - An assessment of soil-to-plant concentration ratios for some natural analogues of the transuranic elements. AB - A field study was conducted in an area of enhanced, natural radioactivity to assess the soil to edible vegetable concentration ratios (CR = concentration in dry vegetable/concentration in dry soil) of 232Th, 230Th, 226Ra, 228Ra, and the light rare earth elements (REE's) La, Ce and Nd. Twenty-nine soil and 42 vegetable samples consisting of relatively equal numbers of seven varieties were obtained from 11 farms on the Pocos de Caldas Plateau in the state of Minas Gerais, Brazil. This region is the site of a major natural analogue study to assess the mobilization and retardation processes affecting Th and the REE's at the Morro do Ferro ore body and U series radionuclides at a nearby open pit U mine. Thorium (IV) serves as a chemical analogue for quadrivalent Pu and the light REE's (III) as chemical analogues for trivalent Am and Cm. The geometric mean CR's (all times 10(-4] decreased as 228Ra (148) greater than 226Ra (76) greater than La (5.4) greater than Nd (3.0) = Ce (2.6) greater than 232Th (0.6), or simply as M (II) greater than M (III) greater than M (IV). These differences may reflect the relative availability of these metals for plant uptake. Significant differences were found in the CR's (for any given analyte) among many of the vegetables sampled. The CR's for the different analytes were also highly correlated. The reasons for the correlations in CR's seen among elements with such diverse chemistries as Ra-REE or Ra-Th are not clear but are apparently related to the essential mineral requirements or mineral status of the different vegetables sampled. This conclusion is based on the significant correlations obtained between the Ca content of the dried vegetables and the CR's for all of the elements studied. PMID- 2909502 TI - Migration of radionuclides controlled by several different migration mechanisms through a sandy soil layer. AB - Column experiments have been carried out on the migration of 60Co and 137Cs through a sandy soil layer in order to examine the migration of radionuclides controlled by several different migration mechanisms. Radionuclide concentration distribution between the effluent and the sandy soil layer was measured after 10 L of the solution containing the radionuclides were introduced into the column from the top of the layer at a constant flow rate. Most of the 60Co and 137Cs remained attached to the layer, and a small amount of each radionuclide; at concentrations of 0.3 and 0.1%, respectively; flowed out from the soil layer. The migration of the mobile fraction of these radionuclides is different from that expected of an ideal cation. These results suggest that the mobile fraction of these radionuclides migrates as non-cationic forms which are not adsorbed into the soil matrix by equilibrium ion exchange. PMID- 2909503 TI - International system of units. PMID- 2909504 TI - Sources for Pu in near surface air. AB - This paper provides evidence that most of the Pu in the near surface air today is due to resuspension. Vertical and particle size distribution in near surface air over a period of three years were measured. The seasonal variations of Pu in air and the influence of meteorological parameters on these variations are shown. Samples were taken before the Chernobyl accident in an area where only Pu fallout from the atmospheric nuclear tests of the early sixties occurs. The comparison of the behavior of Pu with other trace elements, which were also measured, showed similar behavior of Pu and elements like Ca, Ti and Fe in near surface air. This confirms that most Pu is resuspended because the main source for these elements in air is the soil surface. Resuspension factors and resuspension rate are estimated for all measured elements. A resuspension factor of 0.8 X 10(-8) m-1 and a resuspension rate of 0.09 X 10(-9) s-1 is calculated for Pu. PMID- 2909505 TI - Bioassay alpha spectrometry: energy resolution as a function of sample source preparation and counting geometry. AB - Alpha particle counting is based on the response of an electronic counting system to an incident alpha particle. Alpha spectrometry is used in our employee surveillance bioassay program to measure the concentration of isotopes of Am, Pu and U contained on sample source preparations. Nuclides of Am, Pu and U are separated from the sample matrix by anion exchange and are electroplated on a stainless steel disc (Gautier and Gladney 1986). The plated source diameter is 12.7 mm. A tracer is added to the sample before anion exchange as a quality control procedure to provide a measure of chemical yield. Tracer alpha-particle emissions are recorded in a preassigned calibrated area of the energy spectrum and chemical recovery is calculated by the ratio of tracer counts per second divided by the tracer activity in becquerels (Bq). Percent tracer recovery may also be calculated by introducing the average counting efficiency factor in the denominator. Tracer yield is then used to provide a reliable estimate of the sample's analyte counts that are recorded in other preassigned energy dependent areas of the spectrum. The tracer spectrum in the presence or absence of other nuclides also provides evidence of the performance characteristics of the alpha spectrometer, for example, chamber vacuum and electronics. Electroplated samples are counted in any one of 96 detectors. The backgrounds of these detectors are maintained at less than 3 counts per 70,000 s over a 190 keV energy window to provide a limit of detection of less than 0.37 mBq per sample at the 95% confidence level. In this paper, resolution of the photopeak is shown to be a function of the source to detector distance and a function of degraded alpha energies due to Fe or other extraneous materials on the plated surface. Since our program is concerned only with low activity samples (less than 0.2 Bq) we encounter no significant problem with tailing when the resolution is less than 50 keV FWHM. PMID- 2909506 TI - Practical neutron dosimetry with superheated drops. AB - The Superheated Drop Detector (SDD) is a new kind of neutron detector based on the same principle as that of the bubble chamber, except the superheated material is in drop form suspended by a gel or polymer as first described by Apfel (U.S. Patent 4,143,274). Previously, we have developed a theoretical model for the prediction of the threshold neutron energy to nucleate bubbles in our superheated materials and a model for the calculation of the energy dependent response function of SDD. The results of the theoretical calculations agree with the experimental measurements reasonably well. We found the measured response curve of one of our SDDs follows the same trend as the ideal ICRP dose equivalent response curve within 40% for neutrons of energy above 100 keV and within a factor of 10 below 100 keV. Therefore, it is possible to make a rem-response Superheated Drop Detector. We have further calibrated our SDD with 252Cf neutron sources (both bare and D2O moderated). The results are in reasonable agreement with our theoretical predictions, which proves that our model is valid not only for monoenergetic neutrons but also for neutrons from a radioactive source. The principles of operation of our detector, which can be used in neutron dosimetry, area monitoring, and neutron spectrometry, are discussed. PMID- 2909507 TI - Epithelial damage in rabbit corneas exposed to CO2 laser radiation. AB - Corneal injury thresholds are determined for conditions not previously explored for CO2 laser radiation, including multiple-pulse exposures and a systematic investigation of the effect of beam diameter on single-pulse damage thresholds. Multiple-pulse exposures from pulse trains up to 999 pulses, having pulse repetition frequencies between 1 and 100 Hz and individual pulse durations between 10(-3) and 0.5 s, were explored. Damage thresholds are discussed in terms of an approximate critical temperature model, the damage integral model and other empirical correlations. Single-pulse exposures are accurately correlated by an empirical critical temperature model in which the critical temperatures have a weak dependence on exposure duration. However, certain aspects of the single pulse damage data led us to propose a new thermal damage model that incorporates an endothermic phase transition as the damage mechanism. This physical model accurately correlates single-pulse damage for exposures between 10(-3) and approximately 10 s. PMID- 2909508 TI - The kinetics of ligand binding to plant hemoglobins. Structural implications. AB - The rates of reaction of oxygen, carbon monoxide, and nitric oxide with 14 plant hemoglobins have been determined by relaxation and stopped-flow methods. The combination rates for oxygen lie between 0.12 and 0.26 x 10(9)/M.s, for carbon monoxide between 0.01 and 0.07 x 10(9)/M.s, and for nitric oxide between 0.12 and 0.25 x 10(9)/M.s. The dissociation velocities for oxygen range from 5 to 25/s, and for CO from 0.005 to 0.011 s. The oxygen dissociation constants range only from 36 to 78 nM. Nanosecond relaxation experiments show large differences between the proteins. Five have known primary structures which correlate closely with the nanosecond relaxations and less immediately with the millisecond reactions. The relevant amino acid substitutions are concentrated in the C-E interhelical region. PMID- 2909509 TI - Purification and some properties of the small subunit of cytochrome b558 from human neutrophils. AB - We have attempted to purify the heme moiety of cytochrome b558 from human neutrophils. Cytochrome b558 was solubilized from the crude membrane fraction which was pretreated with both 1 M potassium phosphate buffer and 1% octyl glucoside at low ionic strength. The solubilization of cytochrome b558 was carried out efficiently with 1.6% octyl glucoside in the presence of 100 mM phosphate buffer. Solubilized cytochrome b558 was purified by hydroxylapatite, DEAE-Sephacel, and Mono Q fast protein liquid chromatography. The specific content of purified cytochrome b558 was 37 nmol/mg of protein. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of purified cytochrome b558 revealed a single band of 20,000 Da. The large subunit of cytochrome b558, which has been reported by others, could not be found in purified cytochrome b558 even with silver staining. The amino acid composition of the heme-containing moiety of cytochrome b558 was abundant in hydrophobic amino acids. The circular dichroism spectra of both oxidized and reduced b558-type cytochromes exhibited bilobed bands with wavelengths of crossover points closely corresponding to those of the maxima in the optical absorbance spectra at the Soret region. Furthermore, there were some differences in the shoulders and peak widths of CD spectra between oxidized and reduced b558-type cytochromes. These results indicate that this method provides the purification of the small subunit of human cytochrome b558 which is the heme-carrying subunit of cytochrome b558, and suggest that cytochrome b558 has heme-heme interaction and some conformational changes in the alternation of the redox state. PMID- 2909510 TI - Effects of dopamine beta-monooxygenase substrate analogs on ascorbate levels and norepinephrine synthesis in adrenal chromaffin granule ghosts. AB - Chromaffin granule ghosts from bovine adrenal medullae have been used to investigate the effects of prototypic dopamine beta-monooxygenase substrate analogs of two distinct classes on intravesicular reduced ascorbic acid (AscH2) levels and on norepinephrine synthesis. Phenyl-2-aminoethyl sulfide (PAES), a sulfur-containing substrate, was shown to concentrate within ghosts, a process that was time and ATP dependent, but reserpine insensitive. Dopamine beta monooxygenase oxygenation of PAES resulted in accumulation of the oxygenation product, PAESO, without affecting intravesicular levels of AscH2. Similarly, incubations of ghosts with phenyl-2-aminoethyl selenide (PAESe) also resulted in rapid, time- and ATP-dependent, but reserpine-insensitive uptake. However, oxygenation of PAESe by dopamine beta-monooxygenase within ghosts was found to cause a marked decrease in intravesicular AscH2, without buildup of the oxygenated product, phenyl 2-aminoethyl selenoxide. These results illustrate two basic differences between the consequences of PAES and PAESe turnover: while PAES accumulation proceeds concomitant with PAESO production and without AscH2 depletion, PAESe accumulation proceeds with a marked lowering of internal AscH2 but without observable product formation. Both PAES and PAESe were capable of competing with dopamine, the physiological substrate, for enzymatic oxygenation and/or vesicular uptake, and were capable of significantly reducing norepinephrine synthesis. In experiments where ghosts were preincubated with either PAES or PAESe with delayed addition of dopamine, it was clear that neither compound nor their oxygenated products interfered with electron transport via cytochrome b561. These results are consistent with the hypothesis that the physiological activity observed with both PAES and PAESe may be related to their ability to gain entrance to adrenergic neurons and decrease norepinephrine synthesis within neurotransmitter storage vesicles. PMID- 2909511 TI - The membrane-binding segment of dopamine beta-hydroxylase is not an uncleaved signal sequence. AB - Dopamine beta-hydroxylase exists in bovine adrenal medulla chromaffin granules in both soluble and membrane-bound forms. The mechanism by which membranous dopamine beta-hydroxylase is bound to granule membranes has been elusive. Recently, evidence that covalently attached phosphatidylinositol does not serve as an anchor for membranous dopamine beta-hydroxylase was reported (Stewart, L. C., and Klinman, J. P. (1988) J. Biol. Chem. 263, 12183-12186). It was suggested that an uncleaved signal sequence could serve as a mode of attachment for the membrane bound hydroxylase. Amino-terminal sequence analysis of purified bovine membranous dopamine beta-hydroxylase demonstrates that this form of the enzyme possesses an amino-terminal sequence similar to the soluble enzyme. Additionally, the 75- and 72-kDa bands of membranous dopamine beta-hydroxylase were electrophoretically eluted from a preparative sodium dodecyl sulfate-polyacrylamide gel and sequenced. Both bands had the amino-terminal sequence characteristic of the soluble bovine enzyme. These sequence results eliminate the possibility that an uncleaved signal sequence serves as the membrane anchor. PMID- 2909512 TI - A hepatocyte-specific basolateral membrane protein is targeted to the same domain when expressed in Madin-Darby canine kidney cells. AB - Different mechanisms for polarized sorting of apical and basolateral plasma membrane proteins appear to be operative in different cell types. In hepatocytes, all proteins are first transported to the basolateral surface, where sorting (probably signal-mediated) of apical proteins then takes place. In contrast, in Madin-Darby canine kidney (MDCK) cells, proteins are directly transported from the trans-Golgi network to their appropriate plasma membrane domain. In order to study the differences in the sorting requirements of the two cell types, we have expressed a hepatocyte-specific basolateral membrane protein, the asialoglycoprotein receptor H1, in MDCK cells. H1 was found to be specifically transported to the basolateral domain also in this heterologous system, suggesting that either the same basolateral targeting signal is operative in both cell types or, more likely, that basolateral transport occurs "by default," i.e. without the requirement for a sorting signal. PMID- 2909513 TI - Purification and properties of an N-acetylglucosamine-specific lectin from Psathyrella velutina mushroom. AB - A lectin in the fruiting bodies of Psathyrella velutina was purified by affinity chromatography on a chitin column and subsequent ion-exchange chromatography. P. velutina lectin (PVL) tends to aggregate irreversibly in buffered saline, but the addition of glycerol (10%, v/v) to lectin solutions was found to prevent aggregate formation. PVL is assumed to occur as a monomer of a polypeptide of Mr = 40,000 as determined by gel filtration and by gel electrophoresis in the presence of sodium dodecyl sulfate. PVL is specific for N-acetylglucosamine (GlcNAc). It was determined by equilibrium dialysis to have four binding sites/polypeptide molecule showing an average intrinsic association constant of K0 = 6.4 x 10(3) M-1 toward this sugar. The binding specificity of the lectin was studied by hemagglutination inhibition assays and by avidin-biotin-mediated enzyme immunoassays using various GlcNAc-containing saccharides. The results indicate that methyl N-acetyl beta-glucosaminide was a slightly better inhibitor than the corresponding alpha-anomer. PVL binds well to oligosaccharides bearing nonreducing terminal beta-GlcNAc linked 1----6 or 1----3 but poorly to those having a 1----4 linkage, such as N-acetylated chito-oligosaccharides. It also binds to the subterminal GlcNAc moiety when it is substituted at the C-6 position but does not interact with the moiety when substituted either at C-3 or C-4. Thus, these results show that PVL is quite different in its binding specificity from other GlcNAc-binding lectins of higher plants since they bind preferentially to beta-GlcNAc in 1----4 linkage and they have a high affinity for chitin oligosaccharides. PMID- 2909514 TI - Functional characterization of the rat growth hormone promoter elements required for induction by thyroid hormone with and without a co-transfected beta type thyroid hormone receptor. AB - We have extensively characterized the sequences of the rat growth hormone (rGH) promoter required for induction by T3 (thyroid hormone, 3,5,3'-L triiodothyronine) in a transient transfection system. Oligonucleotides containing portions of the rGH promoter sequence with various deletions and point mutations were placed upstream of the first 137 base pairs of the rGH promoter or the heterologous herpes virus thymidine kinase promoter in chloramphenicol acetyltransferase expression vectors. The rGH137 and thymidine kinase promoters show no or minimal response to T3 in the basal state. The constructs were tested in GH4C1 rat pituitary cells and COS cells (functionally deficient in thyroid hormone receptor) with and without a co-transfected plasmid expressing a beta type c-erbA gene coding for a functional T3 receptor. Oligonucleotides containing the T3 receptor binding site confer hormone-dependent induction in a manner that is independent of either orientation or variation in position on the helix relative to the promoter. Point mutations in the sequence -189 to -173 result in loss of T3 induction, and bases between -173 and -167 were also required for a full T3 response. The minimal length to confer T3 induction to the rGH promoter was 23 base pairs (-190 to -167). Point mutations creating a perfect duplication of 7 base pairs within the receptor binding site conferred 12-fold T3 response to the rGH137 promoter, 3-fold greater than the wild type rGH237 construct. T3 inductibility was also transferred to the thymidine kinase promoter by an oligonucleotide containing the sequence -200 to -157, demonstrating that cell type specific elements located 3' to 157 of the rGH promoter are not required for thyroid hormone responsiveness. PMID- 2909515 TI - Phytochrome chromophore biosynthesis. Treatment of tetrapyrrole-deficient Avena explants with natural and non-natural bilatrienes leads to formation of spectrally active holoproteins. AB - Etiolated Avena seedlings grown in the presence of 4-amino-5-hexynoic acid, an inhibitor of 5-aminolevulinic acid synthesis in plants, contain less than 10% of the spectrally detectable levels of phytochrome found in untreated seedlings (Elich, T.D., and Lagarias, J.C. (1988) Plant Physiol. 88, 747-751). In this study, incubation of explants from such seedlings with [14C]biliverdin IX alpha led to rapid covalent incorporation of radiolabel into a single 124-kDa polypeptide in soluble protein extracts. Immunoprecipitation experiments confirmed that this protein was phytochrome. Parallel experiments were performed with four unlabeled linear tetrapyrroles, the naturally occurring biliverdin IX alpha isomer, two non-natural isomers, biliverdin XIII alpha and biliverdin III alpha, and phycocyanobilin-the cleaved prosthetic group of the light-harvesting antenna protein C-phycocyanin. In all cases, except for the III alpha isomer of biliverdin, a time-dependent recovery of photoreversible phytochrome was observed. The newly formed phytochrome obtained after incubation with biliverdin IX alpha exhibited spectral characteristics identical with those of the native protein. In contrast, the spectral properties of phytochromes formed during incubation with biliverdin XIII alpha and phycocyanobilin differed significantly from those of the native chromoprotein. These results indicate that biliverdin IX alpha is an intermediate in the biosynthesis of the phytochrome chromophore and that phytochromes with prosthetic groups derived from bilatrienes having non natural D-ring substituents are photochromic. PMID- 2909516 TI - Thermodynamic and kinetic studies of the interaction of vesicular dipalmitoylphosphatidylcholine with Agkistrodon piscivorus piscivorus phospholipase A2. AB - The tryptophan fluorescence emission intensity at 340 nm of monomeric phospholipase A2 from Agkistrodon piscivorus piscivorus increased about 70% upon addition of dipalmitoylphosphatidylcholine small unilamellar vesicles (DPPC SUV) at 25 degrees C. The emission spectrum was also blue-shifted 6-8 nm, suggesting that the environment of 1 or more tryptophan residues had become less polar. This effect of SUV on the phospholipase A2 fluorescence was independent of Ca2+ at 25 degrees C, and the apparent association constant for the interaction was approximately 1.7 x 10(4) M-1. The apparent Km for hydrolysis of DPPC SUV was equal to the inverse of the estimated association constant. In the absence of Ca2+, the change in fluorescence intensity decreased with increasing temperature. Thermodynamic analysis of this reversible, temperature-dependent fluorescence change indicated that the A. p. piscivorus monomer phospholipase A2 interacts only with SUV in the true gel phase existing below the pretransition of gel to "ripple" phase lipid in the absence of Ca2+. In contrast, the fluorescence intensity change upon addition of SUV in the presence of Ca2+ was independent of temperature over the range of 25-48 degrees C. Under these conditions, hydrolysis of the lipid occurred concomitantly with the change in fluorescence which could not be reversed by the addition of EDTA. With a nonhydrolyzable analog of DPPC, however, the fluorescence changes upon mixing of SUV, Ca2+, and phospholipase A2 were reversible and temperature-dependent. Thus, the apparent irreversibility of the change in fluorescence observed with Ca2+ and DPPC SUV was correlated with hydrolysis of the vesicles. These results indicate that the magnitude of the initial interaction of enzyme with substrate is reversible, is Ca2+-independent, depends upon the lipid state, and is quantitatively correlated to the maximum rate of hydrolysis. PMID- 2909517 TI - Phosphorylation of glucocorticoid receptor-associated and free forms of the approximately 90-kDa heat shock protein before and after receptor activation. AB - Several lines of evidence have suggested that glucocorticoid receptor function may be regulated by phosphorylation-dephosphorylation reactions, and it has been proposed that dephosphorylation accompanies activation to the DNA-binding form. The phosphate content of the approximately 100-kDa steroid-binding protein has been determined directly and was found not to change during activation in intact cells (Mendel, D.B., Bodwell, J.E., and Munck, A. (1987) J. Biol. Chem. 262, 5644 5648). We have now determined the effect of interaction with the receptor and of activation on the phosphate content of the approximately 90-kDa heat shock protein (Hsp 90), which is thought to be a non-steroid-binding subunit of nonactivated glucocorticoid receptors that dissociates on activation. Monoclonal antibodies AC88 and BuGR2 were used to purify free Hsp 90 and cytosolic nonactivated glucocorticoid-receptor complexes, respectively, from WEHI-7 cells grown in the presence of 32Pi and [35S] methionine. Cell-free activation of the nonactivated receptor-antibody complexes immobilized on protein A-Sepharose minicolumns allowed the recovery of the Hsp 90 dissociated from the complexes during activation. Proteins were separated by denaturing polyacrylamide gel electrophoresis, and the 32P/35S ratio, which was used as a measure of the phosphate content relative to protein, was determined for the free, receptor associated, and dissociated forms of the Hsp 90, as well as for the approximately 100-kDa steroid-binding protein of non-activated and activated receptors. The three forms of the Hsp 90 had the same phosphate contents, as did the approximately 100-kDa steroid-binding protein before and after activation. Based upon these results, we conclude that no net change in the phosphorylation occurs when the Hsp 90 associates with the approximately 100-kDa steroid-binding protein to form nonactivated receptors and that neither protein component of nonactivated complexes is dephosphorylated when they dissociate during thermal activation under cell-free conditions. PMID- 2909518 TI - A monoclonal antibody against the platelet fibrinogen receptor contains a sequence that mimics a receptor recognition domain in fibrinogen. AB - The binding of fibrinogen to its platelet receptor, the glycoprotein IIb-IIIa complex, is mediated, in part, by an Arg-Gly-Asp (RGD) sequence within the fibrinogen A alpha chain. PAC1 is an IgM-kappa murine monoclonal antibody that binds to the platelet fibrinogen receptor, and its binding is inhibited by both fibrinogen and RGD-containing peptides. To identify the regions of PAC1 that interact with the fibrinogen receptor, we determined the mRNA sequences of PAC1 immunoglobulin heavy and light chain variable regions. Five out of the six complementarity-determining regions (CDRs) of PAC1 had entirely germline sequences with no regions of similarity to fibrinogen. However, CDR3 of the PAC1 heavy chain (H-CDR3) was very large and unique due to the insertion of a novel D region segment. H-CDR3 contained a sequence, Arg-Tyr-Asp (RYD), that, if present in the proper conformation, might behave like the RGD sequence in fibrinogen. A 21-residue synthetic peptide encompassing the H-CDR3 region inhibited fibrinogen dependent platelet aggregation as well as the binding of PAC1 (Ki = 10 microM) and fibrinogen (Ki = 5 microM) to activated platelets. The RYD region of H-CDR3 appeared to be central to its function, because substitution of the tyrosine with glycine increased the inhibitory potency of the peptide by 10-fold, while replacing the tyrosine with D-alanine or inverting the RYD sequence sharply reduced the inhibitory potency. Thus, the linear sequence, RYD, within H-CDR3 of PAC1 appears to mimic the RGD receptor recognition sequence in fibrinogen. This type of immunologic approach could be useful in studying the structural basis of other receptor-ligand interactions. PMID- 2909519 TI - Cysteine 288: an essential hyperreactive thiol of cytosolic phosphoenolpyruvate carboxykinase (GTP). AB - Phosphoenolpyruvate carboxykinase from the cytosol of rat liver has 13 cysteines, at least one of which is known to be very reactive and essential for catalytic activity (Carlson, G. M., Colombo, G., and Lardy, H. A. (1978) Biochemistry 17, 5329-5338). In order to identify the essential cysteine, this enzyme was modified with the fluorescent sulfhydryl reagent N-(7-dimethylamino-4-methyl-3 coumarinyl)maleimide. Incubation of phosphoenolpyruvate carboxykinase with a 10% molar excess of this maleimide at 0 degrees C results in the rapid and nearly complete loss of catalytic activity. Under these conditions, 1 mol of the maleimide is incorporated per mol inactivated enzyme. The substrate GDP provides almost complete protection against inactivation and modification, while phosphoenolpyruvate protects against the rate, but not the extent, of modification. The pH dependence of the rate of enzyme inactivation suggests that the modified residue has a pK alpha of approximately 7.0. Purification and sequencing of the labeled peptide identifies the hyperreactive essential cysteine as Cys-288. This cysteine lies between two putative phosphoryl-binding domains and within a hydrophobic sequence. PMID- 2909520 TI - Periodate-oxidized 3-aminopyridine adenine dinucleotide phosphate as a fluorescent affinity label for pigeon liver malic enzyme. AB - Treatment of 3-aminopyridine adenine dinucleotide phosphate with sodium periodate resulted in oxidation of the ribose linked to 3-aminopyridine ring and cleavage of the dinucleotide into 3-aminopyridine and adenosine moieties. These two moieties were separated by thin layer chromatography and were synergistically bound to pigeon liver malic enzyme (EC 1.1.1.40), causing inactivation of the enzyme. The inactivation showed saturation kinetics. The apparent binding constant for the reversible enzyme-reagent binary complex (KI) and the maximum inactivation rate constant at saturating reagent concentration (kmax) were found to be 1.1 +/- 0.02 mM and 0.068 +/- 0.001 min-1, respectively. L-Malate at low concentration enhanced the inactivation rate by lowering the KI value whereas high malate concentration increased the kmax. Mn2+ or NADP+ partially protected the enzyme from the inactivation and gave additive protection when used together. L-Malate eliminated the protective effect of NADP+ or Mn2+. Maximum and synergistic protection was afforded by NADP+, Mn2+ plus L-malate (or tartronate). Oxidized and cleaved 3-aminopyridine adenine dinucleotide phosphate was also found to be a competitive inhibitor versus NADP+ in the oxidative decarboxylation reaction catalyzed by malic enzyme with a Ki value of 4.1 +/- 0.1 microM. 3 Aminopyridine adenine dinucleotide phosphate or its periodate-oxidized cleaved products bound to the enzyme anticooperatively. Oxidized 3-aminopyridine adenine dinucleotide phosphate labeled the nucleotide binding site of the enzyme with a fluorescent probe which may be readily traced or quantified. The completely inactivated enzyme incorporated 2 mol of reagent/mol of enzyme tetramer. The inactivation was partially reversible by dilution and could be made irreversible by treating the modified enzyme with sodium borohydride. This fluorescent compound and its counterpart-oxidized 3-aminopyridine adenine dinucleotide may be a potential affinity label for all other NAD(P)+-dependent dehydrogenases. PMID- 2909521 TI - Analysis of DNA-RecA protein interactions involving the protein self-association reaction. AB - A method to analyze the DNA binding properties of RecA protein is developed to take into account the protein self-association reaction and is applied to reanalyze the interaction with chemically modified single-stranded DNA (epsilon DNA). Protein oligomerization is investigated by static light-scattering measurements and analyzed with the accumulated strain model. A coupled equilibrium between DNA binding and self-association of RecA is resolved considering that the complex formed between an m polymer (where m represents the number of units of the polymer) and DNA is identical to the complex resulting from the cooperative binding of m monomers. The cooperativity parameter thus determined is about 10(4), which is more than 100 times higher than the apparent parameter estimated without consideration of the protein oligomerization. This extremely high figure is in good agreement with the formation of large clusters of complex observed by electron microscopy. The apparent DNA binding constant depends upon the ratio of the DNA binding affinity and the self-association constant. For this reason, the variation of the DNA binding constant with the salt concentration is amplified, and the number of ion pairs formed between DNA and RecA obtained from the apparent salt dependence (11 ion pairs/monomer) has been overestimated. Only 2 ion pairs may be formed. PMID- 2909522 TI - Location of the antithrombin-binding sequence in the heparin chain. AB - The antithrombin-binding region of heparin is a pentasaccharide sequence with the predominant structure -GlcNAc(6-OSO3)-GlcA-GlcNSO3(3,6-di-OSO3)-Ido A(2-OSO3)- GlcNSO3(6-OSO3)-. By using the 3-O-sulfated glucosamine residue as a marker for the anti-thrombin-binding sequence, the location of this sequence within the heparin chain was investigated. Heparin with high affinity for antithrombin (HA heparin) contains few N-acetyl groups located outside the antithrombin-binding region, and cleavage at such groups was therefore expected to be essentially restricted to this region. HA-heparin was cleaved at N-acetylated glucosamine units by partial deacetylation followed by treatment with nitrous acid at pH 3.9, and the resulting fragments with low affinity for anti-thrombin (LA-fragments) were recovered after affinity chromatography on immobilized antithrombin. The LA fragments were further divided into subfractions of different molecular size by gel chromatography and were then analyzed with regard to the occurrence of the nonreducing terminal GlcA-GlcNSO3(3,6-di-OS-O3)- sequence. Such units were present in small, intermediate-sized as well as large fragments, suggesting that the antithrombin-binding regions were randomly distributed along the heparin chains. In another set of experiments, HA-heparin was subjected to limited, random depolymerization by nitrous acid (pH 1.5), and the resulting reducing terminal anhydromannose residues were labeled by treatment with NaB3H4. The molecular weight distributions of such labeled LA-fragments, determined by gel chromatography, again conformed to a random distribution of the antithrombin binding sequence within the heparin chains. These results are in apparent disagreement with previous reports (Radoff, S., and Danishefsky, I. (1984) J. Biol. Chem. 259, 166-172; Rosenfeld, L., and Danishefsky, I. (1988) J. Biol. Chem. 263, 262-266) which suggest that the antithrombin-binding region is preferentially located at the nonreducing terminus of the heparin molecule. PMID- 2909523 TI - Conserved and unique amino acid residues in the domains of the growth hormones. Flounder growth hormone deduced from the cDNA sequence has the minimal size in the growth hormone prolactin gene family. AB - Growth hormone (GH), prolactin (PRL), and placental lactogen (PL) constitute a protein family whose genes are considered to have evolved from a common ancestral gene. GHs isolated from various vertebrate species are known to possess highly conserved structural and functional features. In the present study we have cloned and sequenced flounder growth hormone (fGH) cDNA to predict the primary structure of the hormone. The preprotein of fGH is composed of 190 amino acids, and mature fGH is found to be extraordinarily small, having 171 or 173 amino acid residues. The estimated molecular masses of mature fGH are 19.4 to 19.7 kDa. This minimal size of fGH enabled an extended analysis of the essential domains and of amino acid residues required in hormone-specific activities. fGH conserves and shares 37 residues with 20 other vertebrate GHs. These common residues are seen to cluster in five distinct domains (GD1 to GD5). In human PL (hPL), which has low growth-promoting activity, 35 of these 37 residues are conserved, while the other 2 residues in the GD1 domain (Arg-16 and Leu-20) are replaced by Gln and Ala, respectively. In a less active variant of human GH, hGH-V, only 1 residue (His 21) of the 37 residues is replaced by Tyr. Besides these 3 residues, 6 other residues unique to the GHs and some PLs, that is, Ala-24 (GD1), Ser-54 (GD2), Ser 78 (GD3), Leu-106, Leu-116, and Asp-122 (GD4), appear to be important for specific binding of the GHs. The GD5 domain, at the carboxyl-terminal ends of the GHs is considered to be involved mainly in the formation and stabilization of GH molecules. PMID- 2909524 TI - A new folate antimetabolite, 5,10-dideaza-5,6,7,8-tetrahydrofolate is a potent inhibitor of de novo purine synthesis. AB - 5,10-Dideazatetrahydrofolate (DDATHF) is a new antimetabolite designed as an inhibitor of folate metabolism at sites other than dihydrofolate reductase. DDATHF was found to inhibit the growth of L1210 and CCRF-CEM cells in culture at concentrations in the range of 10-30 nM. The inhibitory effect of DDATHF on the growth of L1210 and CCRF-CEM cells was reversed by either hypoxanthine or aminoimidazole carboxamide. Growth inhibition by DDATHF was prevented by addition of both thymidine and hypoxanthine, but not by thymidine alone. 5 Formyltetrahydrofolate reversed the effects of DDATHF in a dose-dependent manner. DDATHF had no appreciable inhibitory activity against either dihydrofolate reductase or thymidylate synthase in vitro, but was found to be an excellent substrate for folylpolyglutamate synthetase. DDATHF had little or no effect on incorporation of either deoxyuridine or thymidine into DNA, in distinct contrast to the effects of the classical dihydrofolate reductase inhibitor, methotrexate. DDATHF was found to deplete cellular ATP and GTP over the same concentrations as those inhibitory to leukemic cell growth, suggesting that the locus of DDATHF action was in the de novo purine biosynthesis pathway. The synthesis of formylglycinamide ribonucleotide in intact L1210 cells was inhibited by DDATHF with the same concentration dependence as inhibition of growth. This suggested that DDATHF inhibited glycinamide ribonucleotide transformylase, the first folate dependent enzyme of de novo purine synthesis. DDATHF is a potent folate analog which suppresses purine synthesis through direct or indirect inhibition of glycinamide ribonucleotide transformylase. PMID- 2909525 TI - The amino acid sequence of rat liver glucokinase deduced from cloned cDNA. AB - Rat liver glucokinase (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1) was purified to homogeneity, cleaved, and subjected to amino acid sequence analysis. Forty-five percent of the protein sequence was obtained, and this information was used to design oligonucleotide probes to screen a rat liver cDNA library. A 1601 base pair cDNA (GK1) contained an open reading frame that encoded the amino acid sequences found in the peptides used to generate the oligonucleotide probes. A second cDNA was subsequently identified (GK.Z2), which is 2346 base pairs long and corresponds to nearly the entire glucokinase mRNA. Blot transfer analysis of hepatic RNA showed that glucokinase mRNA exists as a single species of about 2400 nucleotides. Four hours of insulin treatment of diabetic rats resulted in a 30 fold induction of this mRNA. GK.Z2 has a long open reading frame which, with the known partial peptide sequence, allowed us to deduce the primary structure of glucokinase. The enzyme is composed of 465 amino acids and has a mass of 51,924 daltons. Glucokinase has 53 and 33% amino acid sequence identities with the carboxyl-terminal domains of rat brain hexokinase I and yeast hexokinase, respectively. If conservative amino acid replacements are also considered, glucokinase is similar to these two enzymes at 75 and 63% of positions, respectively. The putative glucose- and ATP-binding domains of glucokinase were identified, and these regions appear to be highly conserved in the hexokinase family of enzymes. PMID- 2909526 TI - Human pepsinogen C (progastricsin). Isolation of cDNA clones, localization to chromosome 6, and sequence homology with pepsinogen A. AB - The entire pepsinogen C (PGC) coding sequence was determined by analysis of a series of five overlapping cDNA clones identified in a library constructed from human gastric mucosa poly(A+) RNA. A partial cDNA clone was initially identified using a 256-fold degenerate oligonucleotide probe for amino acid residues 4-12 of pepsin C, and subsequently 4 additional clones were identified upon rescreening with a probe complementary to the 5' region of the original cDNA clone. Northern analysis of gastric mucosa poly(A+) RNA with a PGC cDNA probe revealed an mRNA 1.5-kilobase species that was indistinguishable from that detected with a human pepsinogen A (PGA) cDNA probe. In contrast, the PGC and PGA cDNA probes detected distinct genomic restriction fragments indicating there was no detectable cross hybridization under high stringency conditions. The PGC gene was localized to human chromosome 6 by analysis of a panel of human x mouse somatic cell hybrids. The regions containing the active site aspartyl groups of PGC are conserved in relationship to several other aspartic proteinases. We propose that the absence of detectable immunologic cross-reactivity between the two groups of human pepsinogens, A and C, results from divergent evolution of sequences located on the surface of the zymogens in contrast to the strongly conserved active site regions located within the binding cleft of the enzymes that are inaccessible for antigenic recognition. PMID- 2909527 TI - Selective binding of L-thyroxine by myosin light chain kinase. AB - L-Thyroxine selectively inhibited Ca2+-calmodulin-activated myosin light chain kinases (MLC kinase) purified from rabbit skeletal muscle, chicken gizzard smooth muscle, bovine thyroid gland, and human platelet with similar Ki values (Ki = 2.5 microM). A detailed analysis of L-thyroxine inhibition of smooth muscle myosin light chain kinase activation was undertaken in order to determine the effect of L-thyroxine on the stoichiometries of Ca2+, calmodulin, and the enzyme in the activation process. The kinetic data indicated that L-thyroxine does not interact with calmodulin but, instead, through direct association with the enzyme, inhibits the binding of the Ca2+-calmodulin complex to MLC kinase. L [125I]Thyroxine gel overlay revealed that the 95-kDa fragment of chicken gizzard MLC kinase digested by chymotrypsin and all the fragments of 110, 94, 70, and 43 kDa produced by Staphylococcus aureus V8 protease digestion which contain the calmodulin binding domain retain L-[125I]thyroxine binding activity, whereas smaller peptides were not radioactive. Since MLC kinase is phosphorylated by cAMP dependent protein kinase (2 mol of phosphate/mol of MLC kinase), the effect of L thyroxine on the phosphorylation of MLC kinase also was examined. L-Thyroxine binding did not inhibit the phosphorylation of MLC kinase and, moreover, reversed the inhibition of phosphorylation obtained with the calmodulin-enzyme complex. These observations support the suggestion that L-thyroxine binds at or near the calmodulin-binding site of MLC kinase. L-Thyroxine may serve as a different type of pharmacological tool for elucidating the biological significance of MLC kinase mediated reactions. PMID- 2909528 TI - Characterization of the promoter region of the human transforming growth factor beta 1 gene. AB - The 5'-end of the human transforming growth factor-beta 1 gene (TGF-beta 1) was isolated from a human leukocyte genomic DNA library. Analysis of the transcriptional start sites of human TGF-beta 1 mRNAs by S1 mapping and primer extension revealed two major start sites 271 nucleotides from one another; several minor sites were also identified. DNA sequence analysis showed that the promoter region contains neither a "TATA" box nor a "CAAT" box, is very G+C rich, and contains 11 CCGCCC repeats. Seven putative binding sites for the transcription factor Sp1 were also identified. To determine the location of sites that may be important for the function of the TGF-beta 1 promoter, we joined the 5'-end of the TGF-beta 1 gene to the coding region for chloramphenicol acetyltransferase. The chimeric gene produced high levels of chloramphenicol acetyltransferase activity in transfected HT-1080, AKR-2B, and A-549 cells. Sequences responsible for both promotion and inhibition of transcription were located in the region extending from 1400 to 300 base pairs upstream of the first major TGF-beta 1 transcriptional start site. The 130-base pair fragment located between 453 and 323 base pairs upstream of this start site contains positive regulatory activity in all cells tested. A second promoter activity was identified in the region between the two major transcriptional start sites. These findings revealed a complex pattern of regulation of human TGF-beta 1 gene expression. PMID- 2909529 TI - Identification of a transcriptional enhancer in a mouse amyloid gene. AB - We have employed a mouse liver-derived cell line (BNL) to identify DNA sequences in the promoter of the serum amyloid A3 (SAA3) gene essential for expression. In both transient DNA transfection assays and BNL cells stably transformed with SAA3 fusion genes, deletion analysis of the SAA3 promoter indicates that sequences between -185 and -138 base pairs 5' to the transcription initiation site are essential for expression of heterologous genes. A 69-base pair sequence spanning this region markedly augmented expression of the bacterial chloramphenicol transacetylase gene regardless of orientation or position. The homology of this sequence with sequences in the promotors of other genes expressed by liver during inflammation suggests a common mechanism of regulation. PMID- 2909530 TI - Purification and characterization of acylation stimulating protein. AB - We have purified to homogeneity and analyzed the amino acid composition of a small (Mr 14,000), basic (pI 9.0) protein from human plasma. This has been named acylation stimulating protein (ASP) because it markedly stimulates triacylglycerol synthesis in human adipocytes. As well, it stimulates triacylglycerol synthesis in human skin fibroblasts cultured from normal individuals. Characteristic saturation curves for the cell metabolic responses to ASP were observed in both cell types with higher stimulation of oleate incorporation into triacylglycerol being observed in adipocytes. The stimulation of triacylglycerol synthesis was much greater with ASP than with insulin. Neither fatty acid binding protein nor albumin was able to mimic the ASP effect. PMID- 2909531 TI - Activation of the vaccinia virus nicking-joining enzyme by trypsinization. AB - The vaccinia virus nicking-joining (NJ) enzyme has been purified to homogeneity from a preparation of virus cores. The virus-specific DNA-dependent enzyme, which does not require ATP, is a single polypeptide of Mr 50,000 and possesses both endonuclease and ligase activities. The principal end product of the enzyme activity, following incubation with closed circular DNA of sufficient linking deficiency, is a linear DNA in which one of the termini has become cross-linked by the in vitro formation of a hairpin. The ability of the NJ enzyme to cross link DNA is significantly enhanced by in vitro proteolysis. The enzymatic properties of the proteolytic digestion product, a 44-kDa polypeptide, differ in several other ways from the intact NJ enzyme. In particular, the specific activity is enhanced and the ionic strength optimum is shifted toward higher salt concentrations. It is suggested that the purified 50-kDa species is a pronuclease that is activated by proteolytic processing. PMID- 2909532 TI - Isolation and characterization of a new immunomodulatory protein, ling zhi-8 (LZ 8), from Ganoderma lucidium. AB - A novel protein with mitogenic activity in vitro and immunomodulating activity in vivo has been isolated from the mycelial extract of an Oriental medicinal fungus, ling zhi (Ganoderma lucidium). This protein was named ling zhi-8 (LZ-8) and its biochemical and immunological properties are described. LZ-8 was purified by two chromatographic systems, gel filtration and followed by ion-exchange, using an in vitro bioassay measuring blast-formation stimulatory activity toward mouse spleen lymphocytes to monitor purification. Analysis by several types of electrophoresis revealed a single band, with the molecular weight differing slightly depending on the system employed. Under reduced conditions, sodium dodecyl sulfate polyacrylamide gel electrophoresis using the method of Laemmli, U.K. ((1970) Nature 227, 680-685) indicated an apparent Mr = 17,100, while under nonreduced conditions an apparent Mr = 17,500 was found; and, using Tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis, a value of apparent Mr = 13,100 was obtained. LZ-8 has an isoelectric point of 4.4, and sugar analysis indicated a low carbohydrate content (1.3%). Half-cysteine, histidine, and methionine were not detected from the analysis of amino acid composition after further purification of LZ-8 by reversed-phase high performance liquid chromatography. LZ 8 was capable of hemagglutinating sheep red blood cells, but no such activity was observed toward human red blood cells (A, B, AB, and O types). In vivo, LZ-8 prevents the production of systemic anaphylaxis reaction in mice if it has been administered repeatedly, and reduction of antibody production is the suggested mechanism. The mechanisms of hemagglutination of sheep red blood cells and of blast-formation stimulation of mouse spleen cells are also discussed. PMID- 2909533 TI - Propylbenzilylcholine mustard labels an acidic residue in transmembrane helix 3 of the muscarinic receptor. AB - Muscarinic acetylcholine receptors were purified from rat forebrain and labeled with [3H]N-(2-chloroethyl)N-(2',3'-[3H2]propyl)-2-aminoethylbenzilate. Cleavage of the labeled muscarinic acetylcholine receptors with a lysine-specific protease yielded labeled, glycosylated peptides about 130 and 200 residues in length, which came from different receptor sequences. The probable cleavage sites are in the second intracellular loop and in the second extracellular or third intracellular loop. The N-terminal 130 residues are disulfide-bonded to another part of the receptor structure, supporting the presence of a link between the second and third extracellular loops. The [3H]propylbenzilylcholine mustard receptor link is cleaved by nucleophiles, acids, and bases under denaturing conditions, suggesting modification of an acidic residue. Cyanogen bromide cleavage points to transmembrane helix 3 as the site of label attachment. PMID- 2909534 TI - The role of caldesmon in the regulation of receptor capping in mouse T-lymphoma cell. AB - Several complementary techniques, including immunocytochemical and immunobiochemical analyses, two-dimensional gel electrophoresis, and peptide mapping, were used in this study to examine the involvement of caldesmon in lymphocyte receptor capping. We have found a lymphoma 140-kDa polypeptide that is structurally similar to muscle caldesmon, suggesting that this polypeptide may be a lymphoma caldesmon. When lymphoma 140-kDa polypeptide is extracted from permeabilized cells using 25 mM MgCl2, capping is inhibited. Adding the 140-kDa protein or gizzard caldesmon back to the extracted cells restores their ability to cap. These findings suggest that actin-linked regulatory proteins such as caldesmon may be critically important to actomyosin-mediated contraction which, in turn, is responsible for collecting receptors into cap structures. PMID- 2909535 TI - Rapid purification and partial characterization of human platelet glycoprotein IIIb. Interaction with thrombospondin and its role in platelet aggregation. AB - Glycoprotein IIIb (also known as glycoprotein IV) is a major glycoprotein present on the surface of human platelets. Recent studies suggest that glycoprotein IIIb may be a receptor site for thrombospondin. Thrombospondin, a multifunctional adhesive glycoprotein released from stimulated platelets, plays an important role in the stabilization of platelet aggregates. In this study, a new method for the purification of glycoprotein IIIb is described. Glycoprotein IIIb was isolated from Triton X-114 platelet membrane extracts, under nondenaturing conditions, by tandem anion-exchange and size exclusion fast protein liquid chromatography. The purified glycoprotein had the same apparent molecular mass (88 kDa) under nonreducing or reducing conditions. The tryptic peptide map of the purified protein was identical to that of bona fide glycoprotein IIIb as isolated from two dimensional polyacrylamide gels of platelet membrane proteins. In addition, the purified glycoprotein was recognized by an anti-GPIIIb monoclonal antibody (OKM5). The purified glycoprotein specifically bound to thrombospondin in the presence of calcium. Monospecific anti-GPIIIb antibodies interfered with the expression of endogenous thrombospondin on thrombin-activated platelets and partially inhibited collagen- and thrombin-induced platelet aggregation without a significant effect on platelet secretion. Glycoprotein IIIb, by interacting with thrombospondin on the activated platelet surface, may play an important role in the platelet aggregation process. PMID- 2909536 TI - Human platelet glycoprotein Ia. One component is only expressed on the surface of activated platelets and may be a granule constituent. AB - Glycoprotein Ia (GP Ia) is a relatively minor component of human blood platelets thought to be a receptor involved in collagen-induced platelet activation. However, some difficulties exist with the definition of this glycoprotein. The expression of GP Ia on resting (prostacyclin analogue-treated) and thrombin activated platelets was compared by surface labeling with 125I-lactoperoxidase. Intact platelets or platelets solubilized in sodium dodecyl sulfate were labeled with periodate/[3H]NaBH4. Analysis on two-dimensional isoelectric focusing/sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels showed that GP Ia is very poorly labeled in resting platelets. After activation a new spot (GP Ia*) appears with the same relative molecular mass as GP Ia under reducing conditions. GP Ia and Ia* can be clearly separated by two-dimensional nonreduced/reduced gel electrophoresis. Therefore, two glycoproteins which have been termed GP Ia exist in platelets with similar molecular weight and pI under reducing conditions. One of these (GP Ia*) is only surface-labeled when platelets are activated, indicating that it is only exposed on the surface of activated platelets. Supernatant from activated platelets contains this glycoprotein as well as other granule components. This glycoprotein is missing in platelets from two patients with collagen-response defects. PMID- 2909537 TI - Human hypoxanthine-guanine phosphoribosyltransferase deficiency. The molecular defect in a patient with gout (HPRTAshville). AB - The genetic basis of hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency has been identified by nucleotide sequence analysis of HPRT cDNAs cloned from a patient with gout. A single nucleotide change was identified in two independent clones: an A to G transition at nucleotide 602. Confirmation of a mutation at this site was provided by RNase mapping analysis. The predicted consequence of this transition is an aspartic acid to glycine substitution at amino acid 201. We have designated this variant HPRTAshville. Prior to this report, enzyme activity in HPRTAshville had not been detected by routine assay. Using more sensitive techniques, including an in situ gel assay for HPRT activity, we were able to demonstrate electrophoretic, kinetic, and structural differences between HPRTAshville and normal HPRT. Electrophoretic migration of HPRTAshville has elevated Michaelis constants for 5-phosphoribosyl-1 pyrophosphate and hypoxanthine. Predicted secondary structural alterations may result from the aspartic acid to glycine substitution. PMID- 2909538 TI - Angiotensin II induces c-fos mRNA in aortic smooth muscle. Role of Ca2+ mobilization and protein kinase C activation. AB - Vasoconstrictors such as angiotensin II (Ang II) play an important role in the pathogenesis of hypertension. These agonists may be responsible for the abnormal vascular smooth muscle cell (VSMC) growth seen in hypertension, either indirectly as a consequence of elevating blood pressure or directly as a result of receptor mediated effects on VSMC growth. To investigate whether Ang II might directly initiate or modulate some of the "early" genetic programs associated with growth in VSMC, the expression of the proto-oncogene c-fos was studied in cultured rat aortic VSMC. Ang II rapidly induced the accumulation of c-fos mRNA, with maximal levels occurring at approximately 30 min. Induction of c-fos mRNA by Ang II was concentration-dependent, with a maximal response at 100 nM. Ang II induction of c fos mRNA was blocked by its competitive inhibitor, [sarcosine 1,isoleucine 8]angiotensin II. Induction of c-fos mRNA was not dependent upon Ang II stimulated intracellular alkalinization or activation of Na+/H+ exchange, but was dependent upon mobilization of intracellular Ca2+ and protein kinase C activation. Epidermal growth factor, a VSMC mitogen, also induced c-fos mRNA in VSMC, but by a mechanism different from that of Ang II. These results demonstrate that the vasoconstrictor hormone Ang II induces in VSMC one of the earliest genes, c-fos, associated with the proliferative response. PMID- 2909539 TI - Molecular cloning of the type 5, iron-containing, tartrate-resistant acid phosphatase from human placenta. AB - The type 5, iron-containing, tartrate-resistant acid phosphatase (TR-AP) constitutes a relatively minor intracellular isozyme of acid phosphatase in the human that is immunologically related to uteroferrin, a secreted progesterone induced protein of the porcine uterus. Here, the purification of small amounts of TR-AP from human placenta is described. When a placental lambda gt11 cDNA library was screened with two short 32P-labeled cDNA clones from within the coding region of uteroferrin, a 1412-base pair cDNA was identified that encodes the entire human TR-AP isozyme. This cDNA contains an open reading frame of 969 base pairs, corresponding to a protein of 323 amino acids. A putative signal sequence of 19 amino acids and two potential glycosylation sites are present. The deduced amino acid sequence of the human TR-AP is 85% identical to that of porcine uteroferrin (whose sequence is also reported here in complete form for the first time) and 82% identical to the corresponding regions of a partial amino acid sequence of a bovine spleen phosphoprotein phosphatase. Northern blotting techniques employing a labeled TR-AP cDNA probe revealed the presence of a 1.5-kilobase transcript in white cells from a patient with hairy cell leukemia, in human K562 erythroleukemic cells, and in Epstein-Barr virus-transformed human B-cells, but not in a human T-cell line. Culture of K562 cells in presence of 10(-8) M phorbol 12-myristate 13-acetate ester for 48-72 h enhanced TR-AP activity per cell about 30-fold and led to a corresponding increase in TR-AP mRNA levels. PMID- 2909540 TI - Post-transcriptional regulation of 3-hydroxy-3-methylglutaryl-CoA reductase mRNA in rat liver. Glucocorticoids block the stabilization caused by thyroid hormones. AB - Administration of dexamethasone to hypophysectomized rats treated with thyroid hormones blocked the increase in hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase mRNA and enzyme activity which occurred in response to thyroid hormone treatment. The rate of transcription of the rat liver HMG-CoA reductase gene measured by "run-on" assays in isolated nuclei was not diminished by dexamethasone. The half-life of HMG-CoA reductase mRNA was decreased from 12 15 to 2-3 h by dexamethasone treatment of hypophysectomized rats fed thyroid powder. Adrenalectomy caused the half-life of HMG-CoA reductase mRNA to increase from 3 to 10 h, suggesting that endogenous glucocorticoids also regulate reductase mRNA stability. Reductase mRNA levels were increased only 5-fold in thyroidectomized rats fed thyroid powder compared to a 20- to 40-fold increase in similarly treated hypophysectomized rats. In thyroidectomized rats, reductase mRNA had a half-life of only 1.5 h. Thyroid hormone treatment increased this to 4.5 h, significantly less than that of similarly treated hypophysectomized rats. Hydrocortisone, like dexamethasone, lowered reductase mRNA levels, but the biologically inactive analogue epihydrocortisone did not affect reductase mRNA or activity. These results suggest that glucocorticoids decrease the abundance of HMG-CoA reductase mRNA by stimulating its degradation. PMID- 2909541 TI - Phosphorylation of caldesmon prevents its interaction with smooth muscle myosin. AB - Caldesmon is known to bind to smooth muscle myosin. Ca2+/calmodulin-dependent phosphorylation of caldesmon completely blocks its interaction with myosin. Cleavage of caldesmon at its 2 cysteine residues by 2-nitro-5-thiocyanobenzoic acid (NTCB) occurs initially at one site to yield 108-kDa and 21.2-kDa peptides and subsequently at the second site within the 108-kDa peptide to yield 85-kDa and 23.5-kDa fragments. The 23.5-kDa peptide retains the ability to bind to myosin. The N-terminal (95 kDa) and C-terminal (42 kDa) chymotryptic peptides of caldesmon were isolated and digested with NTCB: the C-terminal actin- and calmodulin-binding peptide was not cleaved, indicating that it does not contain either of the cysteine residues, whereas the 95-kDa N-terminal peptide was cleaved at two sites to yield 56-kDa, 23.5-kDa, and 21.2-kDa fragments. The arrangement of NTCB fragments in caldesmon is, therefore: 21.2 kDa/23.5 kDa/85 kDa from N to C terminus. Digestion of phosphorylated caldesmon with NTCB suggested a single phosphorylation site in the 21.2-kDa peptide and three sites in the 23.5-kDa peptide. These results lead to the development of a model whereby caldesmon may cross-link actin to myosin and such cross-linking is blocked by phosphorylation of caldesmon. This mechanism may explain the formation of reversible "latch bridges" which permit force maintenance at low levels of myosin phosphorylation in intact smooth muscles. PMID- 2909542 TI - Dual mechanisms of platelet hormone receptor desensitization. Differential importance between agonists of protein kinase C-dependent and -independent pathways. AB - Several different agonists, among them alpha-thrombin, platelet-activating factor, vasopressin, thromboxane A2, and endoperoxides, activate platelets to aggregate and secrete granular contents. Each of these agents is thought to act by inducing the turnover of inositol phospholipids and generating the second messenger molecules inositol 1,4,5-trisphosphate and 1,2-diacylglycerol. However, within minutes, the action of these agonists desensitizes. We have studied the characteristics of this desensitization process for the agonists mentioned above in an attempt to clarify the mechanisms involved. Our results show that two different pathways of desensitization exist, one that is mediated by protein kinase C and another that is independent of this enzyme. In addition, the contribution of these pathways to desensitization differs for the agonists studied. Our data suggest that partial agonists and strong agonists differ in the rate at which the primary response is desensitized rather than in their ability to couple to phospholipase C. PMID- 2909543 TI - Synchronized oscillations in cytoplasmic free calcium concentration in confluent bradykinin-stimulated bovine pulmonary artery endothelial cell monolayers. AB - Bradykinin-evoked rises in [Ca2+]i were measured in fura-2-loaded bovine pulmonary artery endothelial cell monolayers by dual wavelength excitation fluorimetry. In monolayers seeded thinly and grown to confluence, bradykinin, in the presence of external Ca2+, evoked a rise in [Ca2+]i composed of an initial peak and subsequent oscillating plateau. In the absence of external Ca2+, bradykinin evoked a rise in [Ca2+]i which then returned to the basal value without oscillating. In monolayers seeded near confluent density, the bradykinin evoked peak in [Ca2+]i was followed by a steady plateau which showed no oscillation. The addition of the phorbol ester, phorbol 12,13-dibutyrate, to a monolayer during bradykinin-evoked oscillations abolished the oscillations and lowered [Ca2+]i partway back toward the basal level. The addition of the protein kinase C inhibitor, H7, did not abolish oscillatory activity, although the frequency of oscillation was reduced. These results indicate that synchronized oscillatory activity can occur in endothelial cell monolayers. It is suggested that these oscillations are dependent on intercellular coupling developed when the cells are grown to confluence and that the mechanism responsible for generating oscillations in [Ca2+]i requires extracellular Ca2+ and involves protein kinase C. PMID- 2909544 TI - Identification and regulation of a rat liver cDNA encoding farnesyl pyrophosphate synthetase. AB - CR39 is a cholesterol-repressible rat liver cDNA previously isolated by differential hybridization (Clarke, C.F., Tanaka, R.D., Svenson, K., Wamsley, M., Fogelman, A.M., and Edwards, P.A. (1987) Mol. Cell. Biol. 7, 3138-3146). To precisely identify the function of CR39 a fusion protein was constructed that contained the amino-terminal region of the bacterial protein anthranilate synthetase fused to the full length CR39 polypeptide. Affinity purified antisera directed against the fusion protein inactivated rat liver cytosolic prenyltransferase activity in vitro. In addition, affinity purified antisera made to purified chicken prenyltransferase cross-reacted with the fusion protein containing CR39. Rat hepatic prenyltransferase activity and enzyme mass were quantitated in animals fed diets or drugs known to alter endogenous cholesterol biosynthesis. Rats fed a diet supplemented with cholestyramine and mevinolin showed a 3.5-fold increase in activity and a 5.0-fold increase in mass of cytosolic prenyltransferase. A diet supplemented with cholesterol resulted in approximately a 4.0-fold decrease in hepatic enzyme activity and a 10-fold decrease in enzyme mass. Under these same dietary regimens the mass of prenyltransferase in the testes remained unchanged. We conclude that CR39 encodes the prenyltransferase of cholesterol biosynthesis, farnesyl pyrophosphate synthetase. Furthermore, in the liver this enzyme shows coordinate regulation with two other enzymes, 3-hydroxy-3-methylglutaryl-CoA reductase and 3-hydroxy-3 methylglutaryl-CoA synthase, in response to cholesterol feeding and hypocholesterolemic drugs. PMID- 2909545 TI - MG-160. A novel sialoglycoprotein of the medial cisternae of the Golgi apparatus [published eeratum appears in J Biol Chem 1989 Mar 5;264(7):4264]. AB - A monoclonal antibody (mAb 10A8), derived from mice immunized with fractions of the Golgi apparatus from rat brain neurons, was exploited to isolate and partially characterize a novel glycoprotein of 160 kDa apparent molecular mass which was localized by immunoelectron microscopy in medial cisternae of the Golgi apparatus of neurons, glia, pituitary cells, and rat pheochromocytoma (PC 12). The yield of immunoaffinity purified protein was 0.9 microgram/g of rat brain and represented 3% of the Golgi protein; the protein contained asparagine-linked carbohydrates and sialic acid and N-acetylglucosamine residues; unreduced protein had a greater electrophoretic mobility (130 kDa) consistent with the presence of intrachain disulfide bonds. The bulk of the glycoprotein resided within the membrane and/or luminal face of the Golgi cisternae. After extraction with Triton X-114, the glycoprotein was found in both aqueous and detergent phases. The monoclonal antibody did not inhibit the activities of Golgi enzymes or the uptake of nucleotide sugars by intact Golgi vesicles. The findings indicate that the 160 kDa glycoprotein is a specific constituent of medial Golgi cisternae. The results of this study lend support to the hypothesis that the distributions of glycosyltransferases in the Golgi apparatus are cell specific, since in neurons this sialic acid containing glycoprotein is found in medial rather than in trans and/or in the trans Golgi reticulum cisternae, where sialyltransferases have been localized in other cells. Alternatively, resident neuronal Golgi sialoglycoproteins may acquire sialic acid in trans elements of the apparatus and then shuttle back in medial cisternae. PMID- 2909546 TI - An upstream region of the rat luteinizing hormone beta gene binds estrogen receptor and confers estrogen responsiveness. AB - Regulation of gonadotropin gene expression by sex steroids may occur via direct effects on the pituitary and/or by indirect effects of steroid on the hypothalamus. To study direct estrogen regulation of the rat luteinizing hormone beta (LH beta) gene, we performed estrogen receptor-DNA binding studies and transient expression gene transfer experiments. Nitrocellulose filter binding studies were performed with purified estrogen receptor from calf uterus and labeled fragments of the LH beta gene. Dose-dependent specific binding to receptor occurred only with LH beta gene fragments containing a common 284-base region from -1388 to -1105 bases upstream from the transcriptional start site. This DNA region contained a 15-base imperfect palindromic region (GGACACCATCTGTCC) with sequence similarity to other estrogen-responsive elements. Biological function was tested by inserting portions of the 5'-flanking region of the gene next to the herpes simplex virus thymidine kinase promoter fused to the chloramphenicol acetyltransferase gene (LH beta-tkCAT) and performing gene transfer experiments with the pituitary GH3 cell line. Promoter activity in LH beta-tkCAT constructs containing LH beta gene sequences from bases -2013 to -613, or from bases -1388 to -613 in either orientation, exhibited stimulation with 17 beta-estradiol (E2) treatment; in contrast, constructs containing bases -885 to 613 were not regulated by E2. Positive regulation by E2 exhibited dose- and time dependent stimulation, with a maximum 2- to 6-fold effect achieved after 48 h of treatment with 10(-8) M E2. The estrogen receptor appeared to be required for this biological response. Stimulation of LH beta-tkCAT constructs did not occur in L cells with undetectable levels of E2 receptor, but did occur after cotransfection of an LH beta-tkCAT construct and an expression vector containing the human estrogen receptor cDNA. These studies demonstrate that a 5'-flanking region of the rat LH beta gene can bind to the estrogen receptor and that this region can confer hormonal responsiveness to a heterologous promoter. Thus, positive steroid regulation of luteinizing hormone may occur directly on the pituitary at the level of the LH beta gene. PMID- 2909547 TI - A 2.0-A structure of the blue copper protein (cupredoxin) from Alcaligenes faecalis S-6. AB - The structure of a blue copper protein, cupredoxin, from the potent denitrifying bacterium Alcaligenes faecalis S-6, has been determined and refined against 2 A x ray diffraction data. The agreement between observed and calculated structure factors is 0.159, and estimated errors in coordinates are 0.09-0.15 A. The protein folds in a beta sandwich similar to plastocyanin and azurin and includes features such as a "kink" and a "tyrosine loop" which have been noted previously for these proteins as well as immunoglobulins. The copper is bound by four ligands, in a distorted tetrahedral arrangement, with Cu-S gamma = 2.07 A (Cys 78), Cu-N delta 1 = 2.10 and 2.21 for His-40 and His-81, and Cu-S delta = 2.69 A (Met-86). Two of the ligands are further oriented by hydrogen bonds either to other side chains (Asn-9 to His-40), backbone atoms (NH...S) or a water molecule (to His-40). The methionine ligand has no extra constraints. The C-terminal loop containing three of the ligands is hydrogen-bonded to the strand containing His 40 by hydrogen bonds between the conserved residues Thr-79 and Asn-41. The pronounced dichroism of the crystal is a result of the orientation of the normal to the C beta-S gamma-Cu plane parallel to the crystallographic 6-fold axis. PMID- 2909548 TI - Evidence against the importance in the disease process of antibodies to bovine thyroid-stimulating hormone found in some patients with Graves' disease. AB - The antibody to TSH (TSH-Ab) found in some patients with Graves' disease may be either an antiidiotype (anti-id-Ab) to the TSH receptor antibody (TRAb) or the antigen (idiotype) for which the anti-id-Ab is in fact TRAb. Four groups have found antibodies to bovine TSH (bTSH-Ab) in Graves' disease patients in a TSH binding-inhibiting immunoglobulin (TBII) RRA that uses [125I]bTSH. In this assay serum samples containing bTSH-Ab give highly negative TBII values. The purpose of this study was to look for any clinical significance of potential idiotypic antiidiotypic network regulation related to bTSH-Ab. Twenty-one (0.49%) of 4285 Graves' disease patients had TBII values less than the mean -4 SD of normal subjects. In all 21, bTSH-Ab was found by incubation of [125I]bTSH with the patient's serum, and significant inhibition of binding of bTSH-Ab to bTSH by human TSH was found in only 3 of these serum samples. We investigated next whether the binding site of the anti-TSH-Ab mimicked the TSH receptor-binding site. Binding of [125I]bTSH to bTSH-Ab-positive serum was not inhibited by bTSH Ab-negative, thyroid-stimulating immunoglobulin-positive [(+)], and/or TBII(+) immunoglobulin G. In one patient with human TSH-Ab, TSH-Ab appeared and disappeared, and when TSH-Ab was negative, TBII was positive. Inhibition of [125I]bTSH binding to TSH-Ab by the same patient's serum when that patient was serum thyroid-stimulating immunoglobulin(+), TBII(+), and TSH-Ab-negative was sought but not found. Changes in serum TSH-Ab activity and disease activity were not correlated in this patient. In six untreated patients with Graves' hyperthyroidism with bTSH-Ab, the serum T3 and T4 concentrations and the time required to become euthyroid during antithyroid drug treatment were not significantly different from those in 52 such patients without bTSH-Ab. These data suggest that bTSH-Ab is not an anti-id-Ab to TRAb and that TSH-Ab does not directly modulate the activity of Graves' disease. PMID- 2909549 TI - Safe and effective treatment of osteoporosis with intermittent slow release sodium fluoride: augmentation of vertebral bone mass and inhibition of fractures. AB - The value of intermittent slow release sodium fluoride treatment in the management of osteoporosis was studied by a comprehensive metabolic and clinical assessment during a long term trial. Its effect was compared with that of a large dose of 1,25-dihydroxyvitamin D [1,25-(OH)2D] given for a short period preceding each fluoride treatment period in another group of randomly selected patients. The 24 patients in group I (3 idiopathic and 21 postmenopausal) received cyclic treatment in repeated 5-month cycles; each cycle was initiated by 1,25-(OH)2D (2 micrograms/day) for 2 weeks, followed for 3 months by sodium fluoride (slow release, 25 mg twice daily) with 25-hydroxyvitamin D (50 micrograms twice weekly) and calcium supplements (to bring total calcium intake to 1500 mg/day), and was concluded by 6 weeks of 25-hydroxyvitamin D and calcium supplementation without sodium fluoride. The 21 patients in group II (3 idiopathic and 18 postmenopausal) received the same treatment, except for the omission of 1,25-(OH)2D. In both groups, the serum fluoride level was maintained within 5-10 mumol/L (95-190 ng/mL) during fluoride treatment, and serum osteocalcin concentrations correlated positively with the duration of treatment. However, vertebral bone mineral content (L2-L4) did not increase significantly in group I, whereas it rose significantly in group II (fractional change, +0.031/2.4 yr in group I vs. + 0.118/2.9 yr in group II; P less than 0.005). Although bone histomorphometric analyses disclosed overall improvement in both groups, only group II had significant increases in the mineral apposition rate [0.5 +/- 0.2 (+/- SE) to 1.4 +/- 0.2 micron/day; P less than 0.05] and the adjusted apposition rate (0.2 +/- 0.1 to 0.7 +/- 0.1 micron/day; P = 0.04). The vertebral fracture rate significantly declined in both groups, but more so in group II. Excluding the first year of treatment, the fracture rate during treatment in group II of 0.03/patient yr was significantly lower than that of 0.28/patient yr in group I (P less than 0.05). The treatment was well tolerated in both groups; only 16% of patients had either gastrointestinal or rheumatic complications. We conclude that intermittent sodium fluoride treatment without 1,25-(OH)2D provides safe and effective treatment of osteoporosis, marked by formation of new adequately mineralized bone, a rise in vertebral bone mass, and reduced frequency of vertebral fractures. The addition of 1,25-(OH)2D treatment before initiation of each fluoride phase yielded a less favorable response. PMID- 2909550 TI - Effect of oral zinc administration on prolactin and thymulin circulating levels in patients with chronic renal failure. AB - High serum PRL and low zinc (Zn) levels are common findings in patients with chronic renal failure (CRF); in such patients serum Zn concentrations have been reported to be inversely correlated to serum PRL levels. Moreover, Zn regulates both thymus growth and the biological activity of the thymic hormone thymulin, and PRL-thymic interrelationships have been described. To determine whether hypozincemia alters serum PRL and plasma thymulin concentrations in CRF, 9 men with CRF treated by chronic hemodialysis were given 400 mg/day Zn sulfate, orally (4.96 meq/day Zn), for 6 months. Before treatment, serum PRL levels were significantly higher (P less than 0.001) in these patients than in normal men [mean, 28.7 +/- 20.7 (+/-SD) vs. 7.5 +/- 3.7 micrograms/L], and their serum PRL response to TRH (200 micrograms, iv) was impaired (mean maximal percent increase, 38.2 +/- 10.9 vs. 641 +/- 335; P less than 0.001). The plasma Zn-bound bioactive thymulin titer (1.3 +/- 0.7 1/log2), total thymulin titer (Zn-bound plus Zn unbound forms, 2.1 +/- 0.8 1/log2), and serum Zn (13.1 +/- 2.4 mumol/L) were lower (P less than 0.001) in men with CRF than in normal men. Zn therapy did not induce any significant change in basal and TRH-stimulated serum PRL levels, while serum Zn levels significantly increased, reaching the normal range after the first week of treatment (17.8 +/- 6.3 mumol/L). Plasma total thymulin increased rapidly, reaching normal levels after 1 week, but Zn-bound thymulin increased modestly during the first month of treatment and more after 3 and 6 months of treatment. There was no age-related difference in plasma thymulin levels during therapy. We conclude that oral Zn administration in patients with CRF significantly increases both total and Zn-bound thymulin, but does not modify basal and TRH-stimulated serum PRL levels. The observation that Zn supplementation markedly increased plasma thymulin levels in uremic patients suggests that Zn is a potent stimulus for thymic hormone synthesis, and it can reverse the age-related diminution of thymic activity in CRF patients. PMID- 2909552 TI - Effects of estrogens and calcium on calcitonin secretion in postmenopausal women. AB - The protective action of estrogens on bone mass may be mediated by an increase in calcitonin (CT) secretion. We reevaluated this hypothesis using a method for measuring CT in extracts of serum that allows sensitive specific measurement of CT monomer. We studied seven healthy postmenopausal women before and on the 7th and 28th days of each of three 4-week treatment periods: estrogen (estradiol valerate; 2 mg/day), calcium supplement (1500 mg/day), and estrogen plus calcium; the three cycles were separated by intervals of 4 weeks. Serum extractable CT (exCT) levels were measured before and after a short calcium stimulation test (2 mg Ca/kg in 5 min) to assess the C-cell secretory response on each day. Estrogen had the expected biological effects, decreasing (P less than 0.05) serum gonadotropin concentrations and fasting or 24-h urinary calcium excretion. The calcium supplement caused a significant increase in 24-h urinary calcium excretion. However, there was no increase in basal or stimulated serum exCT levels during any of the three cycles. On the contrary, basal serum exCT concentrations decreased slightly but significantly during estrogen treatment from 1.9 +/- 0.5 (+/- SE) to 1.5 +/- 0.4 ng/L on day 7 and 1.2 +/- 0.2 ng/L on day 28 (P less than 0.05). This decrease in basal exCT levels did not occur during the combined estrogen and calcium administration period, probably because the slight decrease in serum calcium induced by estrogen did not occur during combined estrogen and calcium administration. In summary, estrogens do not stimulate CT secretion; variations in serum exCT levels appear to be related to the changes in bone metabolism induced by estrogens. PMID- 2909551 TI - Regional adiposity patterns in relation to lipids, lipoprotein cholesterol, and lipoprotein subfraction mass in men. AB - Anatomical adipose tissue distribution patterns are reported to relate to plasma lipids and risk of cardiovascular disease. Waist to hip girth ratios (WHR) and subscapular 10 triceps skinfold thickness ratios (STR) were compared with percent body fat and body mass index values as correlates of plasma lipids and lipoprotein cholesterol and serum lipoprotein subfraction mass by analytic ultracentrifugation in 81 sedentary middle-aged men in a typical range of adiposity. WHR was significantly and positively correlated with plasma concentrations of triglycerides, cholesterol, and low and very low density lipoprotein (LDL and VLDL) cholesterol and inversely correlated with high density lipoprotein (HDL) cholesterol. STR followed these trends, though less strongly, in relation to plasma triglycerides, VLDL cholesterol, and HDL cholesterol. Pronounced differences were found between regional adiposity patterns in their relationships to lipoprotein subfractions, as determined by analytic ultracentrifugation. WHR was negatively correlated with HDL2 (flotation rate F(1.2) 3.5-9), positively with small LDL (S.f 0-7), intermediate density lipoprotein (S.f 12-20), and VLDL (S.f 20-400), while STR correlated with larger LDL (S.f 7-12) and larger VLDL (S.f 60-400). Overall adiposity was not significantly associated with plasma lipoprotein levels after adjusting for regional adiposity patterns. Plasma sex hormone-binding globulin and percent free testosterone were associated with regional adiposity, but did not account for the correlations between WHR and lipoproteins. WHR and STR are measures of fat distribution that correlate with plasma lipoprotein profiles consistent with cardiovascular disease risk and have different relationships to lipoprotein mass subfractions. PMID- 2909553 TI - Effects of growth hormone on the tempo of sexual maturation in female rhesus monkeys. AB - The signal that initiates and maintains the developmental change in LHRH and, consequently, LH secretion in primates, thus regulating the tempo of puberty, is not known. Given the close association between reproductive development and bone maturation, we examined the hypothesis that GH was involved in developmental increases in LH release, specifically by augmenting the decrease in estradiol (E2) negative feedback inhibition of LH that characterizes late puberty in primates. Recombinant human GH (rhGH; 250 micrograms/kg) was given (sc) three times weekly to immature female rhesus monkeys to determine if developmental increases in basal serum LH would occur at an earlier age, and if menarche and first ovulation also would be advanced. The study groups included intact females receiving rhGH (INT + GH; n = 5), intact control animals (INT; n = 6), ovariectomized females receiving E2 plus rhGH (E2OVX + GH; n = 5), and E2-treated ovariectomized control monkeys (E2OVX; n = 4). The females were studied from 20 months of age until their serum LH levels increased (E2OVX groups) or until the occurrence of first ovulation (intact groups). After 12 months of rhGH treatment, the crown-rump lengths were significantly increased, regardless of ovarian status, an effect maintained in the intact females through 21 months of treatment. The mean age at the time of the initial rise in serum LH was advanced by rhGH treatment in intact females (29.6 +/- 0.4 vs. 31.3 +/- 0.3 months), but not E2OVX females. Subsequent maturational elevations in LH secretion were similar in the E2OVS + GH and E2OVX animals even after an incremental increase in E2. Ages at menarche were similar in the INT + GH and INT groups, whereas first ovulation was significantly advanced in three of five INT + GH females (31.5 +/- 0.7 months) compared to that in INT females (43.5 +/- 0.3 months). The remaining INT + GH females ovulated at an age (42.4 +/- 0.4 months) similar to that of INT females. Those females that ovulated by 32 months had higher skeletal maturity scores than the later ovulating INT females, with the other INT + GH females being intermediate. Furthermore, rhGH resulted in a significant increase in serum E2 levels within 12 h of injection, which remained elevated through 24 h. This effect of rhGH on ovarian E2 secretion did not occur until females had shown elevations in basal serum LH.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2909554 TI - Increased deoxyribonucleic acid synthesis of autonomously functioning thyroid adenomas: independent of but further stimulable by thyrotropin. AB - The percentage of cells in the S/G2M fraction and the cytosol deoxythymidine kinase activity (TKA) were measured in autonomously functioning thyroid adenomas (AFTA) and paranodular tissue (PNT), with special regard to the impact of the patient's serum TSH concentration on DNA synthesis. The S/G2M fraction was determined by means of DNA flow cytometry, and TKA was determined by radioenzyme assay. The S/G2M fraction of AFTA (n = 15, median; 7.1%; range, 3.2-9.2%) exceeded the S/G2M fraction of normal thyroid tissue (n = 8; median, 2.8%; range, 2.3-4.0%; P = 0.008) and in 12 of 13 AFTA was 1.2- to 2.3-fold higher than the S/G2M fraction in the corresponding PNT (median, 4.0%; range, 2.5-6.7%; P = 0.0022). TKA of AFTA (n = 15; median, 681 microIU/mg; range, 432-854 microIU/mg) exceeded TKA of normal thyroid tissue (n = 8; median, 356 microIU/mg; range, 194 426 microIU/mg; P = 0.0001) and was 1.1- to 4.2-fold increased compared with TKA activity in the corresponding PNT (median, 430 microIU/mg; range, 162-570 microIU/mg; P = 0.001). In the absence of measurable serum TSH there was a constant increase in the S/G2M fractions and the TKA in AFTA vs. those in PNT. In patients treated with methimazole with serum TSH concentrations of 0.5 mIU/L or more, the S/G2M fraction and TKA in both AFTA and PNT were significantly higher than those in untreated patients with serum TSH concentrations of 0.5 mIU/L or less. In the majority of AFTA, functional autonomy and increased DNA synthesis are concomitant phenomena. Although TSH may stimulate DNA synthesis in both AFTA and PNT, measurable serum TSH concentrations are apparently not essential for DNA synthesis. PMID- 2909555 TI - Influence of antiopioids on luteinizing hormone pulsatility in aging men. AB - To investigate whether changes in opioid tone play a role in the age-associated changes in LH release in men, the influence of an antiopioid, naltrexone, on plasma LH levels and LH pulses was studied in a group of young and elderly normal men. The young and elderly men had similar basal LH pulse frequencies, but the frequency of high amplitude (greater than 2 IU/L) LH pulses, mean LH pulse amplitude, maximal LH pulse amplitude and pulse area, were lower in the elderly men. Naltrexone administration (40 mg at 0630 and 2200 h the day before blood sampling and at 0630 h, 30 min before starting frequent blood sampling at 10-min intervals for 12 h) to young men (n = 8) induced a significant increase in individual mean baseline plasma LH levels, LH pulse frequency, and the sum of LH pulse amplitudes. In elderly men (n = 11) only a borderline significant increase in baseline plasma LH levels occurred, and neither LH pulse frequency nor the sum of the amplitudes of LH pulses increased. We suggest that in elderly men either opioid tone or the response of the gonadotrophs to endogenous LHRH is decreased. PMID- 2909556 TI - ACC anniversary seminar. Introduction. PMID- 2909557 TI - Coil embolization to occlude aortopulmonary collateral vessels and shunts in patients with congenital heart disease. AB - Gianturco coils were used to embolize 77 vessels in 54 patients: 58 aortopulmonary collateral vessels, 14 Blalock-Taussig shunts, 3 arteries involved in pulmonary sequestrations and 2 venae cavae. Embolization resulted in total occlusion in 53 (69%), subtotal occlusion in 19 (25%) and partial occlusion in 3 (1 intentional). Two embolizations failed to reduce flow. Thus, 72 (95%) of 76 embolizations in which complete occlusion was the intended result resulted in total or subtotal occlusion. Analysis of the results demonstrates that completely occluded collateral vessels were longer and had a smaller diameter than did incompletely occluded vessels. Complications included six cases of inadvertent embolization to the pulmonary arteries (n = 5) or the aorta (n = 1); three were retrieved and three were left without symptoms. In addition, there was a case of severe hemolysis after intentional partial occlusion of a Blalock-Taussig shunt. The results demonstrate that coil embolization can be an effective procedure for managing a wide variety of aorto-pulmonary collateral vessels and shunts in children with congenital heart disease. PMID- 2909558 TI - Endomyocardial biopsy in hemochromatosis: clinicopathologic correlates in six cases. AB - Clinical and pathologic features of cardiac hemochromatosis diagnosed by endomyocardial biopsy in six men, aged 32 to 75 years (mean 52), are described. Echocardiography demonstrated left ventricular enlargement and marked global systolic dysfunction in five. Cardiac catheterization demonstrated normal coronary arteries, increased left ventricular end-diastolic pressure and decreased left ventricular systolic function in all five so studied. Stainable iron was present in all endomyocardial biopsy specimens from the five patients with decreased left ventricular systolic function. Histologically, iron was detected only within the sarcoplasm, and its extent varied inversely with ventricular function. Thus, cardiac hemochromatosis represents a storage rather than an infiltrative disease. These results indicate that stainable iron is consistently observed in endomyocardial biopsy specimens from patients with impaired left ventricular systolic function. Iron staining is recommended for endomyocardial biopsy specimens from patients with idiopathic cardiac dysfunction. PMID- 2909559 TI - Combined automatic implantable cardioverter-defibrillator and pacemaker systems: implantation techniques and follow-up. AB - The automatic implantable cardioverter-defibrillator (AICD) effectively prevents death due to ventricular tachycardia or ventricular fibrillation. Some patients who need an AICD also require cardiac pacing to treat symptomatic bradycardia, bradycardia after defibrillation, or to provide a rate floor to reduce the frequency of bradycardia-related ventricular arrhythmias. Some patients also can benefit from antitachycardia pacing. A mapping technique to implant a pacemaker and AICD sensing leads is presented. For patients with a pacemaker who later need an AICD, the left ventricle is mapped with use of the AICD rate-sensing electrodes to identify a site at which the minimal pacemaker stimulus and maximal ventricular electrogram amplitudes are recorded. An external cardioverter defibrillator that has amplifiers similar to those in the AICD is used to monitor the rate-sensing electrogram. For patients with an implanted AICD, pacemaker implantation is undertaken by mapping the right ventricle with the pacemaker lead while the AICD is in standby mode; the AICD beep monitor is then used to determine a site where pacemaker stimulus detection by the AICD does not occur. Eight patients underwent implantation of a combined AICD-pacemaker system (four ventricular antitachycardia pacemakers, three ventricular demand pacemakers and one atrial demand pacemaker). Neither inhibition of AICD arrhythmia detection nor double counting occurred. Satisfactory AICD-pacemaker function was shown in all patients postoperatively, and no pacemaker malfunction was observed. Thus, with currently available technology, a combined AICD-pacemaker system can be implanted with satisfactory function of both devices and without adverse device-device interactions. PMID- 2909560 TI - Combined automatic implantable cardioverter-defibrillator and pacemaker systems... PMID- 2909561 TI - Angiotensin-converting enzyme inhibition for congestive heart failure: achievements and potential. PMID- 2909562 TI - Clinical experience with sotalol in patients with drug-refractory ventricular arrhythmias. AB - Sixty-five patients with symptomatic, drug-refractory, sustained ventricular tachycardia or fibrillation were treated with oral sotalol (80 to 480 mg twice daily). Sotalol was withdrawn in 11 patients because of continued inducibility of ventricular tachycardia at the time of follow-up electrophysiologic study. Therefore, the clinical effectiveness of sotalol could be evaluated in 54 patients followed up for 11.5 +/- 6 months (range 0.2 to 25). The actuarial incidence of successful sotalol therapy was 54 +/- 13% at 6 months and 47 +/- 13% at 12 months. In 39 patients who underwent electrophysiologic testing while receiving oral sotalol, the drug prevented the reinduction of ventricular tachycardia/fibrillation in 8 (20%). During follow-up study, arrhythmia recurred in 1 (17%) of 6 patients whose ventricular tachycardia was noninducible with oral sotalol and in 8 (44%) of 18 with inducible tachycardia but who were continued on oral sotalol therapy. Adverse effects were noted in 28 patients (42%), requiring drug withdrawal in 13 (22%) and dose reduction after hospital discharge in 10 (15%). Exacerbation of ventricular arrhythmia occurred in six patients (9%), one of whom had associated hypokalemia. Sotalol is frequently useful in the control of intractable, life-threatening ventricular arrhythmias, and its efficacy appears to be predicted by programmed stimulation. However, there is a high rate of limiting side effects, which precludes its use in a large number of patients, and a substantial risk of arrhythmia exacerbation. PMID- 2909564 TI - Direct surgery for ventricular tachycardia: is nonguided misguided? PMID- 2909563 TI - Treatment of life-threatening ventricular arrhythmias with nonguided surgery supported by electrophysiologic testing and drug therapy. AB - Forty-six patients who had coronary artery disease, left ventricular aneurysm and life-threatening ventricular tachyarrhythmia underwent surgical treatment to eliminate or facilitate control of the arrhythmia. Surgery was performed without the assistance of intraoperative mapping techniques. Forty-three patients underwent preoperative or postoperative electrophysiologic testing, or both, and antiarrhythmic therapy was added, when indicated, postoperatively. The patients had a mean age of 63 years, a mean preoperative left ventricular ejection fraction of 27 +/- 9% and a mean preoperative left ventricular end-diastolic pressure of 23 +/- 9 mm Hg. Twenty-one patients (46%) underwent surgical treatment within 2 months of their last myocardial infarction. The overall operative mortality rate was 6.5% (three patients). Eighteen of the 43 operative survivors were discharged from the hospital on no antiarrhythmic therapy, whereas 25 received additional antiarrhythmic treatment. During a mean follow-up period of 36 months (range 2 to 88), there were 13 deaths; eight patients died suddenly, three died of congestive heart failure, one of myocardial reinfarction and one from a noncardiac cause. The overall cumulative cardiac mortality rate at 1, 2 and 3 years was 16, 22 and 35%, respectively, whereas the sudden cardiac death rate was 5, 12 and 20%, respectively. This experience suggests that high risk patients who undergo nonguided surgery for life-threatening ventricular arrhythmia and left ventricular aneurysm have a relatively low surgical mortality and a better long-term survival than previously reported. However, if utilized, such an approach must be systematically supported by perioperative electrophysiologic testing to determine the need for supplemental antiarrhythmic therapy. PMID- 2909565 TI - Effects of ventricular fibrillation and defibrillation on pacing threshold in the anesthetized dog. AB - The effects of transthoracic and internal defibrillation on the bipolar ventricular pacing threshold in 20 anesthetized dogs were examined. Ventricular pacing was accomplished with a computer-controlled, constant voltage pacemaker that permitted rapid determination of pacing threshold. Defibrillation at various energy levels was administered during ventricular pacing and after ventricular fibrillation of 5, 15, 30, 45, 60 or 120 s duration in the 20 dogs. Defibrillation during pacing or within 15 s after initiation of ventricular fibrillation did not significantly increase threshold, regardless of defibrillation energy or mode of delivery. Defibrillation after ventricular fibrillation lasting greater than or equal to 30 s increased (p less than 0.05) threshold determined 6 s after defibrillation. The increase in threshold (in volts) determined 6 s after defibrillation was an exponential function of fibrillation duration (30 s = 0.30 +/- 0.09 V; 45 s = 0.53 +/- 0.13 V; 60 s = 2.24 +/- 1.05 V), but was independent of defibrillation energy or mode of delivery. Threshold returned to control values 15 to 30 s after defibrillation. Cardiopulmonary bypass to maintain coronary perfusion prevented the increase in pacing threshold even after ventricular fibrillation of up to 2 min duration. Pacing threshold is not increased by transthoracic or internal defibrillation, but is increased by ventricular fibrillation of sufficient duration to create substantial myocardial hypoxemia. PMID- 2909566 TI - Prolonged abnormalities of left ventricular diastolic wall thinning in the "stunned" myocardium in conscious dogs: time course and relation to systolic function. AB - Myocardial reperfusion after reversible ischemia is known to be associated with prolonged abnormalities of systolic contractile function (myocardial "stunning"). However, no information is available regarding the recovery of diastolic function in the stunned myocardium in the conscious state. Accordingly, 10 conscious dogs instrumented with pulsed Doppler thickening probes underwent a 15 min occlusion of the left anterior descending coronary artery followed by 7 days of reperfusion. Regional systolic function was assessed as net systolic thickening fraction. Left ventricular regional diastolic properties were estimated from two variables: the mean rate to half end-diastolic thinning and the late diastolic thinning fraction. Both indexes of diastolic function remained severely impaired after restoration of flow. In general, the recovery of the mean rate to half end diastolic thinning and of the late diastolic thinning fraction paralleled the recovery of systolic thickening, but the impairment of the mean rate to half end diastolic thinning was more marked than that of the late diastolic thinning fraction. At 4 h of reperfusion, the values for the mean rate to half end diastolic thinning and the late diastolic thinning fraction (expressed as percent of baseline) were 57 +/- 5% (p less than 0.001 versus baseline) and 79 +/- 7% (p less than 0.05), respectively, whereas systolic thickening fraction averaged 52 +/- 10% (p less than 0.001). At 24 h, the mean rate to half end-diastolic thinning and the late diastolic thinning fraction were no longer significantly different from baseline, whereas systolic thickening fraction remained decreased at 82 +/- 4% (p less than 0.001) and returned to control values by 48 h. This study demonstrates the presence of profound, prolonged abnormalities of regional diastolic wall thinning after a brief episode of ischemia in the conscious state and expands the concept of myocardial stunning from the traditional notion of impaired systolic performance to that of a global derangement in mechanical function that involves both systolic and diastolic properties. PMID- 2909567 TI - Decreased coronary flow reserve after transient myocardial ischemia in dogs. AB - The effect of a transient (15 min) period of regional ischemia on coronary flow reserve in the postischemic myocardium was studied in 24 open chest dogs. Coronary flow was measured with electromagnetic flow probes, and flow reserve was determined during reactive hyperemia after 30 s coronary occlusions and during intracoronary infusions of adenosine. Measures of flow reserve after 15 min of ischemia were made after coronary flow returned to basal levels and flow reserve was then monitored for 1 h. All measures of coronary flow reserve were significantly reduced after transient ischemia: peak flows during reactive hyperemia and intracoronary adenosine infusions decreased by 20 and 24%, respectively, the peak/basal flow ratio by 16% and the repayment/debt ratio by 54%; minimal coronary vascular resistance during reactive hyperemia and intracoronary adenosine increased by 29 and 33%, respectively. Abnormal flow reserve was present for at least 1 h. No changes in flow reserve were detected in control animals over the same time period. Thus, a transient period of myocardial ischemia significantly decreases coronary flow reserve for a prolonged period of time. This "vascular stunning" must be considered when flow reserve is used to assess the functional significance of a coronary stenosis and could be the cause of variable exercise tolerance in patients with angina pectoris. PMID- 2909568 TI - Quantitation of myocardial perfusion by contrast echocardiography: analysis of contrast gray level appearance variables and intracyclic variability. AB - Hand-agitated diatrizoate meglumine/diatrizoate sodium (MD-76) was injected above the aortic valve in seven dogs during two-dimensional echocardiographic imaging to determine the ability of contrast appearance variables (i.e., peak background subtracted gray level intensity, time to peak contrast appearance and maximal slope of the contrast appearance curve) to predict myocardial blood flow. Regional perfusion was altered by a critical coronary stenosis (around the left anterior descending coronary artery) or by administering intracoronary adenosine (into the left circumflex coronary artery), or both. Changes in regional blood flow between control and interventions were compared with the changes in the contrast appearance variables. In addition, the ability of intracyclic variability of gray level intensity to predict myocardial perfusion was assessed. In the determination of absolute myocardial perfusion, background-subtracted peak gray level intensity and the maximal slope of the appearance curve demonstrated a fair correlation (r = 0.67 and 0.51, respectively, p less than 0.0001). However, time to peak contrast appearance did not correlate (r = 0.14, p = 0.31). Intracyclic variability of gray level intensity at control (before contrast injection) and after contrast injection also did not correlate with perfusion (r = 0.18 and 0.06, respectively). In the evaluation of relative changes in myocardial blood flow, the percent change in the maximal slope of the appearance curve correlated with the percent change in blood flow (r = 0.77, p less than 0.0001). Seven of the eight regions with greater than 3.5-fold increase in blood flow were identified by an increase in maximal slope of greater than 50%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2909569 TI - Ventricular defibrillation using biphasic waveforms: the importance of phasic duration. AB - Biphasic waveforms can be used to defibrillate the heart with less energy than that used by monophasic waveforms. In 14 anesthetized open chest dogs with large contoured defibrillation electrodes, the effect on defibrillation efficacy of varying the duration of the two phases of biphasic waveforms was studied. All combinations of 0, 1, 3.5, 6 and 8.5 ms duration were used for both the first and the second phase except for the meaningless case in which both durations were 0 ms. The 3.5-2 waveform (3.5 ms first phase and 2 ms second phase) was also tested. All the hearts were defibrillated with less than or equal to 5 joules using any of the 25 waveforms. However, biphasic waveforms with the second phase shorter than or equal to the first had significantly lower defibrillation thresholds than did those with the second phase longer than the first or than did monophasic waveforms of approximately the same total duration. A plot of defibrillation threshold current strength versus second phase duration for all biphasic waveforms with a 3.5 ms first phase did not produce a hyperbolic strength-duration curve as seen with monophasic waveforms. To verify these findings, defibrillation dose-response curves were obtained for the 3.5-2, 6-6 and 3.5-8.5 biphasic waveforms in another six dogs. The 50 and 80% successful voltage doses of the 3.5-8.5 waveforms were significantly higher than those of the other two waveforms, which were not different from one another.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2909570 TI - Shortening of ventriculoatrial intervals with left bundle branch block during orthodromic reciprocating tachycardia in three patients with a right-sided accessory atrioventricular pathway. AB - Previous studies of the effects of bundle branch block on ventriculoatrial (VA) intervals during orthodromic reciprocating tachycardia have focused on the timing of the atrial electrograms. However, left bundle branch block importantly affects the timing of initial ventricular activation, and this effect would also be expected to affect VA intervals during orthodromic reciprocating tachycardia. Presented here are three patients with a single right-sided accessory atrioventricular pathway exhibiting left bundle branch block during orthodromic reciprocating tachycardia. Each had shortening of the VA interval by 10 to 30 ms during left bundle branch block beats. This shortening was accompanied by a nearly equal increase in the HV interval, with the His bundle to atrial interval remaining constant. It is concluded that the timing of ventricular as well as atrial electrograms impacts on the VA intervals with left bundle branch block beats during orthodromic reciprocating tachycardia. With left bundle branch block, delay in initial left septal activation results in later onset of the QRS complex and, with right ventricular activation occurring normally, shortening of the VA interval occurs in patients with a right-sided pathway. PMID- 2909571 TI - Fluid dynamics model of mitral valve flow: description with in vitro validation. AB - A lumped variable fluid dynamics model of mitral valve blood flow is described that is applicable to both Doppler echocardiography and invasive hemodynamic measurement. Given left atrial and ventricular compliance, initial pressures and mitral valve impedance, the model predicts the time course of mitral flow and atrial and ventricular pressure. The predictions of this mathematic formulation have been tested in an in vitro analog of the left heart in which mitral valve area and atrial and ventricular compliance can be accurately controlled. For the situation of constant chamber compliance, transmitral gradient is predicted to decay as a parabolic curve, and this has been confirmed in the in vitro model with r greater than 0.99 in all cases for a range of orifice area from 0.3 to 3.0 cm2, initial pressure gradient from 2.4 to 14.2 mm Hg and net chamber compliance from 16 to 29 cc/mm Hg. This mathematic formulation of transmitral flow should help to unify the Doppler echocardiographic and catheterization assessment of mitral stenosis and left ventricular diastolic dysfunction. PMID- 2909572 TI - Doppler color flow evaluation of prosthetic mitral valves: experimental epicardial studies. AB - More than 300 epicardial Doppler color flow mapping studies on 23 different types of clinical and preclinical valves were performed after implantation in the mitral position in sheep. The transducers were placed directly on the heart to obtain the greatest possible resolution. Studies were performed in each animal under different hemodynamic conditions by varying heart rate and cardiac output. Eighty-six valves were studied late (20 to 52 weeks), whereas the remainder were studied early (0 to 10 days) after operation. The valves included 3 types of ball and cage valves, 3 types of disc and cage valves, 7 types of tilting disc valves, 1 type of bileaflet hemidisc mechanical valve, 13 types of porcine aortic valves and 5 types of bovine pericardial valves. The results of these studies were compared with those obtained in 40 studies of 20 native mitral valves. Doppler color velocity/flow profiles were imaged in real time with simultaneous electrocardiographic gating; the aortic flow was also displayed for the timing of velocity/flow events. Native normal mitral valves had no in-orifice flow disturbances and laminar low velocity/flow directed toward the left ventricular apex. Ball and cage and disc and cage valves had high velocity peripheral jets and vortices of velocity/flow reversals distal to the occluders. Tilting disc valves had differing velocity/flow patterns determined by their orientation in the mitral anulus. Bileaflet hemidisc valves had three jets, which decayed 1.5 cm downstream. Porcine aortic and bovine pericardial bioprosthetic valves had high velocity, turbulent, nonaxisymmetric jets (more severe for the latter).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2909573 TI - Spatial velocity distribution and acceleration in serial subvalve tunnel and valvular obstructions: an in vitro study using Doppler color flow mapping. AB - To evaluate the spatial distribution of flow velocities, turbulence and spatial acceleration in serial tunnel-valve obstruction, Doppler color flow mapping was performed in a pulsatile flow model with a tunnel obstruction (1.0 or 1.5 cm2) inserted at 2, 20 and 40 mm proximal to a mildly stenotic bioprosthetic valve studied at flow rates of 1, 2.7 and 4.9 liters/min. Measured pressure gradients were consistently higher across the tunnel (mean +/- SD 32.7 +/- 26.5 mm Hg) than across the tunnel plus valve (28.8 +/- 26.9 mm Hg, p less than 0.01). Doppler color flow map images were analyzed using a Sony RGB video-digitizing computer, providing numerical velocity assignments for the blue, red and green (variance) pixel components to allow the flow maps to be constructed into digital velocity maps and pseudo three-dimensional velocity maps. The maximal velocity stream extended distal to the tunnel (2 to 19 mm), and the length of this extension correlated well with the pressure gradient measured across the tunnel (r = 0.89), with a rapidly decelerating and turbulent spray area seen immediately distal to the valve. Pressure gradient calculated from the maximal velocity derived from the color flow map, which could only be estimated from the velocity maps for the 1.5 cm2 tunnel, correlated well with the gradient measured across the tunnel (18.0 +/- 14.1 versus 19.2 +/- 14.5 mm Hg, respectively, r = 0.98). Acceleration was seen proximal to both tunnels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2909574 TI - Guidelines for ambulatory electrocardiography. A report of the American College of Cardiology/American Heart Association Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (Subcommittee on Ambulatory Electrocardiography). PMID- 2909575 TI - Detection of amiodarone pulmonary toxicity. PMID- 2909576 TI - Dilated cardiomyopathy in myotonic dystrophy. PMID- 2909577 TI - Quantitative exercise thallium-201 variables versus cardiac catheterization. PMID- 2909578 TI - Elderly patients with hypertrophic cardiomyopathy: a subset with distinctive left ventricular morphology and progressive clinical course late in life. AB - This report describes a subgroup of 52 elderly patients with obstructive hypertrophic cardiomyopathy in whom certain clinical and morphologic features differed importantly from those of many other patients with this disease. Ages ranged from 60 to 84 years (mean 69) and 45 [87%] were women. Echocardiographic examination showed a relatively small heart, having only modest ventricular septal hypertrophy associated with marked distortion of left ventricular outflow tract morphology. By virtue of selection, left ventricular outflow tract size at end-diastole was substantially reduced, and anterior displacement of the mitral valve within the left ventricular cavity was particularly marked. Sizable deposits of calcium in the region of the mitral anulus, posterior to the mitral valve, appeared to contribute to the outflow tract narrowing. Systolic anterior motion of the mitral valve was severe (with apposition of the mitral valve and ventricular septum) in 32 patients and more moderate in 20. The mechanism by which systolic contact between the mitral valve and septum occurred in most patients appeared to differ from that observed more typically in many other patients with hypertrophic cardiomyopathy; in most elderly study patients, anterior excursion of the mitral valve leaflets was relatively restricted, and systolic apposition between the mitral valve and septum resulted from a combination of anterior motion of the mitral valve and posterior excursion of the septum. The vast majority (50 of 52) of the patients remained asymptomatic (or only mildly symptomatic) for most of their lives and often did not develop severe and intractable symptoms until the 6th or 7th decade (ages 56 to 81 years; mean 66). Of the 49 patients with at least 1 year follow-up study, only 12 had improvement with pharmacologic therapy; however, 14 of the 18 patients who underwent ventricular septal myotomy-myectomy or mitral valve replacement obtained symptomatic benefit from operation. In conclusion, obstructive hypertrophic cardiomyopathy in many elderly (and predominantly female) patients may assume a distinctive morphologic appearance and a progressive clinical course. This subgroup of patients appears to constitute an important segment of the disease spectrum of hypertrophic cardiomyopathy of cardiac disease in the elderly that previously has not been precisely defined nor fully appreciated. PMID- 2909579 TI - An acquired disease component in hypertrophic cardiomyopathy: new clinical clarifications. PMID- 2909580 TI - Radionuclide angiographic assessment of left ventricular diastolic filling in amyloid heart disease: a study of patients with familial amyloid polyneuropathy. AB - To assess left ventricular diastolic filling in amyloid heart disease, 17 patients with familial amyloid polyneuropathy and 20 normal subjects were examined by radionuclide angiography. None of the patients showed clinical evidence of restrictive cardiomyopathy. All but two patients had normal left ventricular ejection fraction. Peak filling rate was significantly lower and time to peak filling rate was significantly greater in patients than in normal subjects (2.60 +/- 0.52 versus 3.10 +/- 0.44 EDV/s, p less than 0.001, and 215 +/ 53 versus 147 +/- 18 ms, p less than 0.001, respectively). The mean left ventricular filling volume during rapid diastolic filling and atrial systole in patients was 54.5 +/- 19.5% and 44.2 +/- 21.6% of the stroke volume, respectively, compared with 83.8 +/- 6.6% (p less than 0.001) and 20.0 +/- 6.0% (p less than 0.001), respectively, in normal subjects. Although 10 of the 14 patients without clinical evidence of overt heart disease had normal ventricular wall thickness as well as normal ejection fraction, 8 of the 10 showed abnormal diastolic filling. In patients with familial amyloid polyneuropathy, indexes of diastolic filling were significantly related to ventricular wall thickness alone. The incidence and magnitude of abnormalities in time to peak filling rate and contribution of rapid filling as well as atrial systole to ventricular filling increased with age and duration of illness. Thus, abnormal diastolic filling can be seen even in the early stage of familial amyloid polyneuropathy and may be related to myocardial amyloid deposition as well as to fibrosis. Careful consideration should be given to age and duration of illness when diastolic filling is assessed in this disorder. PMID- 2909581 TI - Diastolic dysfunction in amyloid heart disease: restrictive cardiomyopathy or not? PMID- 2909582 TI - The St. Jude valve prosthesis: analysis of the clinical results in 815 implants and the need for systemic anticoagulation. AB - Between July 1979 and December 1984, 785 patients received 815 St. Jude Medical valve prostheses. Valve-related mortality in the follow-up period was due to thromboembolism in seven cases, anticoagulant-related hemorrhage in three and perivalvular leak in two. Freedom from valve-related death or reoperation at 3 years was 96.4% for aortic valve replacement and 98.3% for mitral valve replacement. The overall rate of thromboembolism was 2.6%/patient-year with warfarin, 9.2%/patient-year with antiplatelet medication and 15.6%/patient-year in patients with no anticoagulant therapy. One episode of thrombotic obstruction of a mitral valve, in a patient receiving no anticoagulant therapy, resulted in an occurrence rate of such obstruction of 0.22%/patient-year. Valve replacement with the St. Jude valve produced excellent clinical results, but long-term anticoagulation with warfarin was required to minimize thromboembolic complications. The use of antiplatelet agents alone provided inadequate protection. PMID- 2909583 TI - Aortic regurgitation: a common complication after surgery for hypertrophic obstructive cardiomyopathy. AB - Surgical ventriculomyectomy and ventriculomyotomy by the aortic approach are safe and effective methods of relieving symptoms and obstruction to left ventricular outflow in patients with hypertrophic obstructive cardiomyopathy. With the addition of Doppler ultrasound to the routine follow-up assessment of these patients an unexpectedly high occurrence of aortic regurgitation was found in the postoperative patients. Because aortic regurgitation has been reported to rarely accompany this condition, 67 patients with hypertrophic obstructive cardiomyopathy were studied clinically and with Doppler echocardiography for the presence and severity of aortic regurgitation. Severity of the regurgitation was quantitated by pulsed or color Doppler echocardiography according to the length and width of the regurgitant jet in at least two views. In 37 patients with hypertrophic obstructive cardiomyopathy who did not undergo surgery, aortic regurgitation was detected in only 1 (3%) by Doppler ultrasound and in none clinically. In 52 patients who did undergo surgery and were studied a mean of 7.8 years postoperatively, aortic regurgitation of trivial to moderate degree was common, being detected in 28 (54%) by Doppler ultrasound and in 6 (12%) clinically. In a subgroup of 22 patients who were studied preoperatively and again early postoperatively (mean 6 weeks), new aortic regurgitation was found in 8 (36%) and was graded as trivial in all. Aortic regurgitation is a common complication related to ventriculomyectomy and ventriculomyotomy in patients with hypertrophic obstructive cardiomyopathy. Although initially trivial, the regurgitation may progress in severity over time. The regurgitation has been well tolerated in all patients studied to date. PMID- 2909584 TI - Accuracy of cardiac output measured by continuous wave Doppler echocardiography during dynamic exercise testing in the supine position in patients with coronary artery disease. AB - To estimate the accuracy of cardiac output measured by continuous wave Doppler echocardiography from the suprasternal notch and the utility of this method for evaluating left ventricular function during dynamic exercise, simultaneous thermodilution and Doppler cardiac output were measured in 34 patients with coronary artery disease during multistage ergometer exercise in the supine position. Cardiac output was measured at rest and during each stage of exercise. Twenty-five of the 34 patients whose thermodilution curves were adequate for analysis were studied during exercise. The correlation coefficient for the two methods was 0.85 at rest and 0.84 during exercise. Differences between the two methods were not significant at rest but were significant during exercise, with the thermodilution method giving the higher values. Underestimation by the Doppler method is probably due to technical problems and changes in aortic diameter during exercise. The 25 patients were classified into two groups according to pulmonary artery wedge pressure at peak exercise. There were 11 patients in Group 1 pressure (greater than or equal to 20 mm Hg at peak exercise) and 14 in Group 2 pressure (less than 20 mm Hg at peak exercise). There were significant differences in the change in cardiac index and in peak aortic velocity from rest to peak exercise between the two groups. A significant linear correlation between the percent change in peak aortic velocity and in pulmonary artery wedge pressure from rest to peak exercise was observed (r = -0.66, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2909585 TI - Transesophageal Doppler color flow imaging in the detection of native and Bjork Shiley mitral valve regurgitation. AB - Regurgitant blood flow of mitral valves was studied by transesophageal Doppler color flow echocardiographic imaging in 11 healthy volunteers (Group 1), 25 cardiac patients with a native mitral valve (Group 2), 10 patients with a normally functioning Bjork-Shiley mitral prosthesis without clinical evidence of mitral regurgitation (Group 3) and 10 patients with angiographic or surgical evidence of Bjork-Shiley mitral valve regurgitation (Group 4). Holosystolic regurgitant color jets were classified as type I or type II. The data were compared with results obtained with precordial techniques, i.e., continuous wave and Doppler color flow echocardiographic imaging (Groups 1 to 4) and left ventricular angiography or surgery (Groups 2 and 4). In Group 1, transesophageal Doppler color flow imaging revealed no mitral regurgitant flow in 7 of the 11 patients and a type I jet in 4 patients that was detected in only 1 patient by precordial techniques. In Group 2, angiography showed no mitral regurgitation in 20 patients and documented mitral regurgitation in 5. Transesophageal Doppler color flow imaging detected in 4 of the 20 patients a type I jet that was not visualized with precordial techniques in 2 patients. Type II jets were detected by the transesophageal technique in all five patients with proven mitral regurgitation and were also visualized with precordial echocardiography. All patients in Group 3 showed two identical type I jets that were not detected with precordial echocardiography.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2909586 TI - Suggested guidelines for use by dietitians in the interpretation of indirect calorimetry data. PMID- 2909587 TI - Position of the American Dietetic Association: nutrition management of adolescent pregnancy. PMID- 2909588 TI - More reflections on the 100th monkey. PMID- 2909589 TI - Eating disorders: the clinical dietitian's changing role. PMID- 2909590 TI - The dietitian as the nutrition counselor: the 1989 Journal. PMID- 2909591 TI - Eating disorders among selected female student populations at UCLA. AB - Seven hundred sixteen female UCLA students--drawn from Primary Care Clinic, Women's Health Clinic, sorority, athletic team, dance major, and undergraduate psychology class populations--completed questionnaires regarding eating disorders symptoms and attitudes compatible with the diagnostic criteria published by the American Psychiatric Association in the Diagnostic and Statistical Manual, (3rd ed., DSM-III), the Eating Disorders Inventory, and related information. The purpose of the study was to determine the prevalence of eating disorders and eating disorder-related symptoms in particular subgroups for targeting intervention and prevention programs. Although between 7.5% and 46% of subgroup populations reported the presence of individual eating disorder-related symptoms, the prevalence of active eating disorders for the group as a whole at the time of the survey was 2.1%, with the prevalence of disorders at any time during life 4.8%, using DSM-III diagnosis. The Eating Disorders Inventory scores for the group as a whole were comparable with norms reported by other researchers in the literature. Primary Care Clinic attenders and dance majors reported the highest rates of symptoms and disorders, while athletes reported the lowest rates. PMID- 2909592 TI - Energy intake and dietary macronutrient content in women with anorexia nervosa and volunteers. AB - This study was designed to compare the dietary intakes of patients with anorexia nervosa and normal controls. Twenty-four patients hospitalized for treatment of anorexia nervosa were compared with 10 normal controls. Patients ate a self selected diet and maintained their admission weight to within 1.0 kg during this period (19 +/- 3 days). Food chosen by each subject was weighed before and after meals, and intake was determined to be the difference. Intakes of food energy, protein, fat, and carbohydrate were calculated. Patients were closely monitored to ensure that no disposal of food occurred. Patients with anorexia nervosa had a mean daily energy intake of 1,017 +/- 54 kcal (mean +/- SEM), significantly lower than the mean energy intake for controls (1,651 +/- 108 kcal). Similarly, mean intakes of macronutrients (41 +/- 4 gm protein, 34 +/- 2 gm fat, and 136 +/- 9 gm carbohydrate) were significantly lower for patients than for controls (68.5 +/- gm protein, 65 +/- 6 gm fat, and 204 +/- 13 gm carbohydrate). However, when protein, fat, and carbohydrate were assessed as a percent of total calories, there were no significant differences between patients and controls. There were also no significant differences in calories consumed per kilogram body weight. Underweight patients with anorexia nervosa who maintain their weight on an unrestricted hospital diet have energy intake per kilogram body weight and dietary macronutrient content indistinguishable from those of normal women. PMID- 2909593 TI - Relationship between nutrient intake, body mass index, menstrual function, and ballet injury. AB - The effects of inadequate nutrition, menstrual dysfunction, and low body weight on the injury rate of ballerinas were studied. Forty-nine female ballet dancers, mean age 18.7 years, completed food frequency and injury questionnaires. Subjects were placed in one of two groups: those with an intake less than 70% of the Recommended Dietary Allowances (RDA) for key nutrients and those with an intake greater than 70% of the RDA for key nutrients. Sixty-nine percent of the dancers had intakes less than 70% of the RDA and were randomly assigned to either a vitamin/mineral supplement or to placebo for 6 months. The remaining dancers with diets adequate (greater than 70% RDA) in key nutrients received no treatment. All groups were questioned monthly about the incidence, severity, and nature of ballet injuries. Information regarding menses and height and weight was obtained. There were no significant differences in the severity or type of injuries among the dancers in the supplement, placebo, or no treatment groups. Dancers with abnormal menses had more bone injuries (mean = 15.00) than normally menstruating dancers (mean = 4.97) (p less than .05). Dancers with a Body Mass Index less than 19.0 spent more days with a low-grade injury (mean = 24.05) than dancers with a greater BMI (mean = 11.63) (p less than .05). There appears to be a relationship between dance injuries and both BMI and menstrual function. PMID- 2909594 TI - Nutrition and growth retardation in 10 children with congenital deaf-blindness. AB - This study describes the nutritional intake, growth, and early food habits of 10 Norwegian children born deaf and blind. They were 1 girl and 9 boys aged 8 to 23 years. A 4-day dietary record, anthropometric measurements, and interviews with the parents were obtained. The children had energy intakes below or in the lower range of the reference values given in the Recommended Dietary Allowances (RDAs). Intakes of vitamins and minerals were acceptable when supplements were taken into account. Despite low physical activity, all pupils were thin. The interviews with the parents revealed early and serious feeding problems that arose at weaning. At the same time, growth retardation was registered for a majority of the pupils. All pupils were described as strikingly thin while growing up. We conclude that the early feeding problems were so pronounced that malnutrition may be considered a contributing factor to the growth retardation. PMID- 2909595 TI - The team concept in supervised practice: benefits for students and preceptors. AB - Economic pressures in health care today make it difficult for many practitioners to provide educational opportunities for dietetic students. Staff members at practice settings, with increased responsibilities on the job, stipulate limitations on the numbers of students and request that they be better prepared. Dietetic educators are faced with maintaining the quality of supervised practice, particularly for new students, in spite of reduced availability of practice settings and time limitations of staff preceptors. An option is the multiple assignment--a technique in which students function as a team. Three students, each with a set of specialized objectives, cooperate in the care of one patient: One is the doer, one is the resource person, and one is the evaluator. This methodology was adapted to dietetics, and a pilot project was conducted in a hospital setting. Three student teams (nine students), three clinical preceptors, and one faculty member participated. Students achieved at high levels and demonstrated great satisfaction in their supervised practice. For staff preceptors, the team approach reduced student-related time involvement by one half and promoted the quality of student performance. Guidelines for further application of the model are given. PMID- 2909596 TI - A nutrition/health training program for Peace Corps volunteers. AB - Nutrition and health education is a crucial component of the overall mission of the Peace Corps program. Individuals selected to work as Peace Corps volunteers need to be well prepared to perform this complex and challenging job in recipient countries. This article presents a model for a training program for Peace Corps trainees that was conducted over a 5-week period. The program was planned in accordance with some specific training guidelines that were provided by the Peace Corps. The trainees included nine women ranging in age from 22 to 61 years with diverse backgrounds; however, all had a BA/BS in a health-related discipline. Training curriculum included fundamental nutrition and health-related areas: basic nutrition, foods, clinical nutrition, maternal and child health, communicable diseases and sanitation, health strategies, and community development. Fifty percent of the curriculum was devoted to "hands-on" practical and clinical activities. Maternal and child health was emphasized in the training curriculum as this is an area of concern in all developing countries. The trainees were evaluated by weekly quizzes as well as completion of a special project involving applications of all their newly acquired skills. Implications of the training program are discussed. PMID- 2909597 TI - Southeast Asian renal exchange list. AB - More than 340,000 Southeast Asians (SE Asians) have immigrated to the United States since 1971. By 1984, 76,000 SE Asians had settled in California. In areas of the U.S. with large SE Asian populations, many foods specific to those people are readily available. Approximately 5% of the total U.S. population has medical problems that lead to kidney disease. Many SE Asian refugees have prior medical problems, such as hepatitis B, that may make them at significantly higher risk for kidney disease. A modified renal exchange list (excluding milk, carbohydrate supplement, and fat group) was developed. This list, made up of foods readily available and commonly eaten by the largest group of SE Asian immigrants, the Vietnamese, categorizes foods by protein, potassium, and caloric content. A separate list, indicating the phosphorus content of these foods, is also included. Asian grocery stores were visited to identify foods available for purchase by SE Asians. The foods were identified, and nutrient composition was found in food composition tables. Because the Vietnamese diet is high in potassium and sodium, planning renal diets poses problems for both patients and dietitians. Close monitoring of diet can retard the progression of renal disease. An exchange list such as this assists both dietitians and renal patients in this important task. PMID- 2909598 TI - Eating patterns and weight concerns of college women. PMID- 2909599 TI - Symptoms of anorexia nervosa in female university dietetic majors. PMID- 2909600 TI - Relationship of body image and dietary intake of competitive ice skaters. PMID- 2909601 TI - The yield of a home visit in the assessment of geriatric patients. AB - Elderly patients often have problems not easily detected during an office visit. We investigated the yield of a home visit by a geriatric nurse specialist as part of an interdisciplinary assessment process. Compared with the findings of an office-based assessment by a general internist, the home visit resulted in up to four new problems (median = 2, mean = 1.7, 95% confidence interval = 1.5-1.8) and one to eight new recommendations (median = 4, mean = 3.6, 95% confidence interval = 3.4-3.9). Twenty-three percent of the problems could have resulted in death or significant morbidity. The most frequent problems related to psychobehavioral difficulties (23.1% of problems involving 38.3% of patients), safety (21.6% of problems involving 35.7% of patients), and caregiver related problems (20.4% of problems involving 33.8% of patients). The most common recommendations related to safety (30.7% of recommendations involving 81.8% of patients), caregiver well being (19.8% of recommendations involving 52.6% of patients), and social issues (12.7% involving 33.8% of patients). Baseline clinical information did not predict the yield of the home visit in this sample. We conclude that an in-home assessment contributes unique and meaningful information to the geriatric assessment process. PMID- 2909602 TI - Benefit from admission to a geriatric assessment and rehabilitation unit. Discrepancy between health professional and client perception of improvement. AB - To determine differences in perception of benefit from a patient's admission to a geriatric Assessment and Rehabilitation Unit, we asked both medical and nursing staff (health team) and the patient and carer (clients) for their evaluation after discharge. The areas studied were functional ability, relief of the principal symptom, education about the principal problem, and development of coping skills. Of 94 patients studied, 58 patients were discharged to the community (52 to carers, 6 to live alone) and 36 to institutions. In the former group, the health team had a consistently higher perception of benefit than the clients (P less than .001). Factors positively predicting health team perception of benefit were a higher carer happiness, improvement in patient independence, and internalization of the patient's locus of control. A negative predictor was an increase in patients' responsibilities. Client perception of benefit was positively predicted by fewer problems with companionship and communication with others. The health team's perception rated the adequacy of patient education and development of coping skills more highly than did the clients. In the patients discharged to the community, their perception of benefit at 1 week was a good predictor of survival in the community to 6 weeks. The possible reasons for these differences in perception of benefit and their implications are discussed. PMID- 2909603 TI - Elderly patients admitted to the psychiatric unit of a general hospital. AB - Elderly psychiatric patients who are cared for in general hospital psychiatric settings have not been clearly characterized in the literature in terms of demographics, primary diagnoses, hospital course, and outcome. The authors reviewed charts of 168 patients over the age of 60 years admitted to a general hospital inpatient psychiatry unit over a 5-year period in order to develop a demographic and clinical profile of this patient population. Results indicated that the large majority of patients had affective syndromes; dementia was the second most common diagnosis. Length of stay correlated with severity of depressive illness, while a diagnosis of dementia was associated with a shorter hospitalization. Outcome measures showed favorable response to treatment in three fourths of this population of elderly psychiatric patients. These data suggest that the general hospital acute inpatient setting is well suited to care for the combined medical and mental illnesses of elderly psychiatric patients. PMID- 2909604 TI - Cortisol deficient state. A cause of reversible cognitive impairment and delirium in the elderly. AB - An elderly female who had suffered a stroke was admitted to the Jewish Institute for Geriatric Care (JIGC) for rehabilitation. Three years previously she was found to have a pituitary macroadenoma (prolactinoma) that was treated with radiation therapy. She had been on thyroid replacement for secondary hypothyroidism. Upon admission she was found to have severe cognitive impairment in association with a low plasma cortisol level. After treatment with prednisone there was a dramatic improvement in cognitive function and the patient was able to participate in a rehabilitation program. PMID- 2909605 TI - Do not resuscitate discussions in a hospital-based home care program. AB - Discussion of code status of a patient is usually raised in the inpatient setting, when patients are unable to participate because of their critical condition. In order to increase patient participation, code status was discussed in the homes of 37 chronically ill patients enrolled in a hospital-based home care program. Twenty patients or conservators did not want resuscitation performed in case of cardiac arrest. In this small, select group, outpatient code discussions benefited the patients, families, and health care providers. PMID- 2909606 TI - Valedictory. PMID- 2909607 TI - Salutatory. PMID- 2909608 TI - Agreement with Churchill: no rationing on the basis of age. PMID- 2909609 TI - Are too many drugs prescribed for the elderly after all? PMID- 2909610 TI - Anthropometric indicators and hip fracture. The NHANES I epidemiologic follow-up study. AB - A cohort of 3,595 white women aged 40-77 years was followed for an average of 10 years during which 84 new cases of hip fracture were identified. Triceps skinfold thickness and arm muscle area measured at baseline were examined as possible risk factors for hip fracture controlling for physical activity, height, menopausal status, calcium consumption, and smoking. Of these variables only arm muscle area, triceps skinfold thickness, and activity in recreation were independent predictors of hip fracture incidence using the Cox proportional hazards model. After adjustment, the estimated relative risk of hip fracture was approximately two for an increment of each anthropometric indicator (adjusted for the other) equivalent to comparing those at the 25th percentile to those at the 75th percentile (maximum width of 95% confidence intervals, 1.2-2.9). Risk of hip fracture was approximately two-fold for persons who reported little recreational exercise compared to persons who reported much recreational exercise (95% confidence interval, 1.2-3.2). Our findings are the first evidence from a prospective study that anthropometric indicators besides body mass index may have an independent relationship to risk of hip fracture. PMID- 2909611 TI - Historical note on hoarseness in mitral valve disease. PMID- 2909612 TI - Thyroid hormones: blood levels do not define status of metabolism. PMID- 2909613 TI - Antigen processing and intracellular Ia. Possible roles of endocytosis and protein synthesis in Ia function. AB - Anti-I-A mAb and monovalent Fab fragments were used to explore the cellular distribution and endocytosis of I-A in peritoneal exudate cells (PEC) and TA3 B lymphoma-hybridoma cells. TA3 cells contained 1.6 x 10(5) I-A sites/cell, 22 to 35% of which were intracellular. This intracellular pool was cycloheximide resistant. PEC contained 1.8 x 10(5) I-A sites/cell, 25 to 40% of which were intracellular. Upon adherence, however, the intracellular pool of I-A in PEC dropped to 2 to 11% of the total cellular I-A. Ag processing by TA3 cells was unaffected 3 h after abrogation of protein synthesis with cycloheximide, suggesting that newly synthesized I-A is not necessary for Ag processing in TA3 cells (post-synthetic processing and transport of I-A to the plasma membrane were complete by 2 h in TA3 cells with or without cycloheximide, as assessed by sequential immunoprecipitation of surface and intracellular I-A). In adherent PEC, however, cycloheximide markedly inhibited Ag processing, suggesting depletion of factors necessary for Ag processing. Ag processing may involve binding of processed Ag peptides to intracellular Ia derived to varying degrees from both endocytosis and new biosynthesis. To explore the possibility of I-A recycling, I-A endocytosis was demonstrated using mAb and monovalent Fab probes; internalization occurred within 5 min and peaked by 10 to 15 min with 15 to 35% of bound antibody in an intracellular compartment, resistant to an acid wash. Subcellular density gradient fractionation demonstrated that I-A and transferrin were processed exclusively in an endosomal fraction of relatively light density, whereas ligands of the mannose receptor were processed in light endosomes and in a distinct, denser population of endosomes, and accumulated in lysosomes. Thus, I A appears to be internalized into a specific population of endosomes that may play a central role in Ag processing. PMID- 2909614 TI - Analysis of the natural polymeric forms of human properdin and their functions in complement activation. AB - Many of the anomalies observed in studies or properdin may be explained on the basis of its ability to form a series of multi-subunit polymers and by differences in the functions of these forms of properdin. Dimers (P2), trimers (P3), tetramers (P4), and higher Mr polymers (Pn) of the 46,000-Da subunit were separated by gel filtration or by cation exchange chromatography of purified properdin. The specific activity of each form was measured in two assays. The native properdin activity of P4 was 10 times that of P2 (on a molar basis) with the order: P4 greater than P3 greater than P2 greater than Pn. During C activation P4 was found to be consumed first, P3 second, and P2 last, consistent with their measured specific activities. Assays for activated properdin showed that only Pn caused fluid phase C consumption when incubated in serum at normal concentrations. Pn accumulated during long term storage of purified P and freezing rapidly converted the smaller oligomers to Pn. The isolated oligomers were extremely stable, but did redistribute after denaturation-renaturation cycles by using low pH or guanidine. Renaturation after exposure of any species to denaturing conditions yielded mixtures of 20:54:26 (P4:P3:P2). This distribution was almost identical to that found in fresh normal human serum or plasma, suggesting that a distinct distribution of oligomers exists in blood that provides the C system with an apparently advantageous range of specific activities. PMID- 2909615 TI - Characterization of the enhanced susceptibility of paroxysmal nocturnal hemoglobinuria erythrocytes to complement-mediated hemolysis initiated by cobra venom factor. AB - When whole serum C is activated by cobra venom factor complexes (CoFBb), paroxysmal nocturnal hemoglobinuria (PNH) III E (the most C-sensitive type) are hemolyzed, but normal and PNH II E (the intermediately sensitive type) are not. Previous studies have shown that after exposure to CoFBb and serum, PNH III E bind relatively large amounts of the trimolecular C complex, C5b67, whereas normal and PNH II E bind virtually none. In the studies reported herein, we have observed that when normal and PNH III E are incubated with isolated C5, C6, and 125I-C7 in the presence CoFBb, the normal E bind more C5b-7 than the PNH cells. When C7-deficient serum is included in the reaction mixture, however, the PNH E are once again observed to bind much greater amounts of C5b-7. These observations suggest that plasma and membrane factors act in concert to restrict the assembly of the trimolecular C5b-7 complex on human E. PNH III E appear to be deficient in the membrane component of this inhibitory system. PMID- 2909616 TI - Antigen-triggered membrane potential changes in IgE-sensitized rat basophilic leukemia cells: evidence for a repolarizing response that is important in the stimulation of cellular degranulation. AB - We have studied Ag-induced membrane potential changes of rat basophilic leukemia cells by using the potential-sensitive dye, bis-(1,3 diethylthiobarbiturate)trimethineoxonol. A rapid membrane depolarization is triggered by a multivalent Ag, and it has a bell-shaped dose dependence that parallels the degranulation response but not the extent of cross-linking of the IgE-receptor complexes. As the temperature is reduced from 37 degrees C, this depolarization response slows and decreases in magnitude until complete inhibition is observed at 15 degrees C, similar to the temperature dependence previously observed for the Ag-stimulated rise in cytoplasmic Ca2+ and for degranulation. The results imply that a highly temperature-dependent step subsequent to Ag binding and cross-linking is necessary for the depolarization response. A partial return to the resting potential is seen to follow the depolarization response to Ag. This repolarization process is inhibited by quinidine.HCl and Ba2+ in parallel with an inhibition of the degranulation response. Repolarization is not affected by 4-aminopyridine or by the absence of K+ in the external buffer. These data suggest that the repolarization is caused by a previously uncharacterized K+ channel. PMID- 2909617 TI - Alterations in the antigenic structure of two major HSV-1 glycoproteins, gC and gB, influence immune regulation and susceptibility to murine herpes keratitis. AB - We previously demonstrated that anterior chamber (AC) injection of HSV-1 before or simultaneous with topical corneal HSV-1 infection resulted in cellular immune tolerance of HSV-1 Ag and a reduced frequency of corneal stromal lesions. In the present study, we have investigated the role of the HSV-1 cell-surface glycoproteins gC and gB in the induction of tolerance, and the resulting reduced susceptibility to HSV-1 corneal stromal disease. These studies utilized mutant strains of HSV-1 with deletion or point mutations in the gene coding for gC or gB. Groups of mice received topical corneal infections with wild-type HSV-1, followed by AC injection of the same eye with wild-type HSV-1 or a mutant strain. Varying the antigenic composition of the virus injected into the AC resulted in three distinct patterns of immune responsiveness. In agreement with our previous findings, AC injection of wild-type HSV-1 induced a state of HSV-1 specific tolerance that extended to both the delayed type hypersensitivity (DTH) and CTL responses. A mutant strain lacking gC (gC-) induced partial tolerance characterized by undetectable CTL activity but a normal DTH response. A mutant strain lacking gB (gB-) caused partial suppression of the CTL response and no reduction of the DTH response. Thus, whereas gB may be involved in CTL tolerance induction in this model, gC clearly is not involved. In contrast, both gC and gB must be present in the AC to induce detectable DTH tolerance. The latter interpretation was strengthened by the observation that AC injection of a mixture of gC- (expressing normal gB) and gB- (expressing normal gC) effectively suppressed the DTH response to wild-type HSV-1. A panel of mar mutants with individual point mutations affecting gC and gB was used to identify the epitopes responsible for induction of DTH tolerance. Two of the gC mutants failed to induce DTH tolerance to wild-type HSV-1 when injected into the AC, suggesting that the sites on the gC molecule that are altered by these mutations are important for the induction of DTH tolerance. Similarly, one of the mar mutants for gB uniformly failed to suppress the DTH response, while another had a variable effect. The unique pattern of cellular immune reactivity exhibited by the mice receiving simultaneous topical corneal infection with wild-type HSV-1 and AC injection of gC- (no CTL but normal DTH) was associated with significantly reduced susceptibility to HSV-1 corneal stromal lesions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2909618 TI - Structural relationships among the H-2 D-regions of murine MHC haplotypes. AB - The number of genes encoding functional Ag-presenting molecules in the D region of the murine MHC differs among haplotypes. For example, the H-2b D region contains a single "D/L" gene, H-2Db, whereas the d-haplotype encodes two, H-2Dd and Ld. Using D/L specific oligonucleotide probes, we have found that, as with H 2d, the q- and v-haplotypes contain two D/L genes, whereas the other haplotype examined have one. Hybridization analysis using cloned probes that map between H 2Dd and Ld revealed similar structures in each of the three haplotypes (d, q, and v) which have "duplicated" D regions. Two approaches were used to examine allelic relationships among the D/L genes. First, the 5' region of the H-2Db gene was sequenced, and found to be more similar to H-2Ld than to H-2Dd. Second, oligonucleotide probes that distinguish H-2Ld from H-2Dd revealed H-2Ld-related genes in several haplotypes, including the duplicated haplotypes H-2q and H-2v. Analogous probes specific for H-2Dd, however, did not detect similar sequences in the other haplotypes. We interpret these results to mean that the three duplicated D regions arose from a common duplication event, and share the five gene structure of the D region cluster defined in H-2d. However, subsequent events have generated sequence divergence at the D-locus. PMID- 2909619 TI - HLA-B51 and HLA-Bw52 differ by only two amino acids which are in the helical region of the alpha 1 domain. AB - Genes encoding the serologically cross-reactive HLA-B51 and HLA-Bw52 molecules were isolated and the exons sequenced. HLA-B51 genes obtained from Caucasian and Oriental individuals were identical. HLA-Bw52 differs from HLA-B51 by four nucleotide substitutions in exon 2 encoding the alpha 1 domain. These comprise one isolated silent substitution in codon 23 and a cluster of three coding substitutions in codons 63 and 67. Amino acid substitutions of N----E at position 63 and F----S at position 67 are the only differences between HLA-B51 and HLA Bw52 and these residues are postulated to form HLA-B51 specific epitopes. HLA-B51 could have been formed from HLA-Bw52 by the combination of a genetic exchange with HLA-B8 and a point mutation. Similarity of HLA-B51 and HLA-Bw52 with HLA Bw58 suggest they also share a common ancestor. PMID- 2909620 TI - Ultrastructural changes in red blood cells following pulsed irradiation in vitro. AB - The careful choice of a combination of laser parameters such as wavelength, pulse duration, and dose has provided a means for confining laser energy to specific targets within tissue such as oxyhemoglobin within the cutaneous microvasculature. In the process of achieving such vascular selectivity, certain ultrastructural changes in red blood cell (RBC) cytoplasm have been observed, such as the generation of intracytoplasmic electron-lucent spherical structures. These structures, ranging in size from 80 to 1000A, were seen in RBCs exposed to laser doses at and above threshold, and appeared to represent a morphologically novel form of highly-specific tissue injury. This in vitro study using RBC in phosphate buffered saline (PBS) was undertaken to better understand the mechanism(s) that could have been responsible for these unique morphologic changes. We conclude that the intracytoplasmic electron-lucent spherical structures seen within RBCs were heat-fixed molds formed around vaporized water bubbles and were not produced by the release of oxygen from the oxyhemoglobin moiety during 577-nm laser irradiation. PMID- 2909621 TI - A method for predicting steady-state rate of skin penetration in vivo. AB - A simple in vivo method was proposed for predicting the steady-state rate of penetration of drugs across the stratum corneum. Both the diffusion coefficient and the partition coefficient in the stratum corneum can be determined by the amounts of drug in the stratum corneum at two time intervals under transient conditions after transdermal drug application. The amount of drug entering the stratum corneum is determined by 20 strippings with an adhesive tape. The steady state rate of penetration was then calculated for the thickness of the stratum corneum and the concentration of the donor solution. The steady-state rates of penetration of ascorbic acid and estradiol across hairless mouse skin were evaluated from this in vivo approach and compared with those obtained from in vitro penetration experiment using excised hairless mouse skin. The data confirmed that the proposed in vivo method can predict the steady-state rate of penetration of these drugs across the stratum corneum in normal skin. PMID- 2909622 TI - Covalently bound lipids of human stratum corneum. AB - In the present study, we demonstrate that human stratum corneum contains covalently bound lipids accounting for 1.4% of the dry weight of the tissue. The major component (53.3% of the total by weight) is a ceramide (CER-A) consisting of 30 through 34-carbon omega-hydroxyacids amide-linked to sphingosine. The other bound lipids in human stratum corneum include fatty acids (12.7%), omega-hydroxy acids (9.4%), and a second, more polar, omega-hydroxyacid-containing ceramide (CER-B, 24.8%). The predominant omega-hydroxyacids in both ceramides, as well as the free hydroxyacid fraction, are the 30-carbon saturated and 32- and 34-carbon monoenoic species. The bound fatty acids consist largely of 14 through 22-carbon saturated species, but significant proportions of monoenoic species and linoleic acid are also present. Psoriatic scale contains a similar total concentration of the same covalently bound lipids, but the proportions of the individual bound lipids are different from those found in normal stratum corneum. It is suggested that the principal function of the covalently bound lipids in human stratum corneum is the formation of a lipid envelope on the outer surface of the keratinized cells. PMID- 2909623 TI - A new model for growth and filament production of Pityrosporum ovale (orbiculare) on human stratum corneum in vitro. AB - A new model for the production of hyphae in Pityrosporum ovale in vitro is described. P. ovale was cultured on human stratum corneum pieces placed directly on a culture medium. The highest number of hyphae (24%) was seen after 6 d of incubation at 37 degrees C in a microaerophilic environment. There was a variation between the strains tested. This model opened possibilities to study the filamentous form of P. ovale in vitro. The effect of antimycotics and variation in antigens may be investigated and compared to the yeast form. PMID- 2909624 TI - Influence of human dermal fibroblasts on epidermalization. AB - Using a method that allowed the reconstruction of simplified living human skin in vitro, we investigated the effects of collagen texture and dermal fibroblasts on epidermal growth. Like in vivo skin, our in vitro model comprised two tissues: a dermal equivalent and an overlying epidermis. It permitted measurement of epidermal growth and therefore evaluation of the effect of the dermal equivalent on this growth. Epidermal growth was enhanced when the collagen matrix had previously been reorganized by fibroblasts, and was greatest when living fibroblasts persisted in this matrix. On cell-free collagen gel and on collagen matrices containing dead fibroblasts, epidermal growth increased when the medium was conditioned by fibroblasts grown in monolayers. We conclude that the function of the fibroblasts is not only to synthesize and degrade the extracellular matrix, but also to regulate epidermalization; on the one hand by remodeling the collagen fibers, and on the other by secreting diffusible factors that promote epidermal growth. These results underline the importance of fibroblasts in dermo epidermal interactions, and show that the skin equivalent culture model provides a way to quantitatively study these interactions. PMID- 2909625 TI - Abstracts for the 1988 annual meeting of the Societe Francaise de Recherche Dermatologique. Grenoble, France, September 15,16, 1988. PMID- 2909626 TI - Epidemiology of Fogo Selvagem. PMID- 2909627 TI - Tissue amyloid P component in normal human dermis is non-covalently associated with elastic fiber microfibrils. AB - Tissue amyloid P component (TAP), a protein that crossreacts immunohistochemically with the normal plasma glycoprotein serum amyloid P component (SAP), is invariably associated with elastic fiber microfibrils in adult humans. We have investigated the nature of this association. Aliquots of minced, homogenized dermis, obtained following ethylenediamine tetraacetic acid (EDTA) separation of whole adult human skin, were extracted with different reagents, and the presence or absence of TAP in the pellet and in the supernatant following centrifugation was determined by SDS-PAGE and immunoblotting using anti SAP antibodies. TAP was extractable from dermis using reagents which disrupt non covalent bonds, including sodium dodecyl sulfate (SDS) and guanidine hydrochloride. TAP was not extracted by high molarity salt solutions, non-ionic detergents, or the reducing agents dithiothreitol and 2-mercaptoethanol. EDTA solution was similarly unsuccessful at eluting TAP from the dermal preparation, indicating that the association of TAP with elastic fiber microfibrils is not simply the result of Ca++-dependent binding. Collagenase solubilized some TAP, but this does not prove covalent linkage to elastic tissue of part of the TAP, because the apparent Mr of TAP extracted was identical to that of normal SAP subunits. We cannot completely exclude the possibility that a few subunits in each multimeric TAP molecule are covalently attached to the microfibrils. However, our findings that denaturing agents alone extracted most of the TAP from normal human dermis strongly suggest that the great majority of the dermal TAP is non-covalently bound to elastic fiber microfibrils. Thus TAP is not an integral constitutent of elastic fiber microfibrils. PMID- 2909628 TI - Increased androgen binding capacity in sebaceous glands in scalp of male-pattern baldness. AB - Sebaceous glands were isolated by manual dissection under a microscope from surgical specimens of scalp skin with male pattern baldness and skin specimens of hairy and bald scalp obtained at autopsy. The 800 X g pellet (nuclear fraction) and the 164,000 X g supernatant fraction (cytosol) of homogenates of the sebaceous glands were used for measurements of androgen binding characteristics, using dextran-coated charcoal and sucrose gradient methods. Scatchard plots showed high affinity binding for [3H]dihydrotestosterone (DHT) and [3H]methyltrienolone (R1881). Nuclei prepared from bald scalp contained greater total androgen binding capacity than nuclei of hairy scalp, although Kd values of type I binding were similar (0.68 vs 0.56 nM, respectively). On sucrose gradient, the binding protein from cytosol was found in the 7 to 8S density range. Androgen binding by cytosol of sebaceous glands of hairy scalp had Kd of 1.89 +/- .79 and 2.05 +/- .56 nM for DHT and R1881, respectively, and Bmax of 18.7 +/- 4.4 and 20.0 +/- 4.6 fmol/mg protein for DHT and R1881, respectively. Cytosol from sebaceous glands of bald scalp had Kd values approximately half those of hairy scalp, and Bmax values 50%-100% higher. The bound 3H labeled DHT and R1881 could be partially displaced by testosterone (40-50%), moxestrol (28-32%), promegestone (19-26%), and delta 4-androstenedione (6-12%), but not by dehydroepiandrosterone. These data demonstrate the presence of specific androgen binding protein in sebaceous glands, and that sebaceous glands of bald scalp have greater binding affinity and capacity for androgens than those in hairy scalp. This difference may explain the greater androgenic response in androgenic alopecia. PMID- 2909629 TI - Amphotericin B induces tumor necrosis factor production by murine macrophages. PMID- 2909630 TI - Cell-mediated immunity to recombinant human immunodeficiency virus (HIV) antigens in HIV-infected populations. PMID- 2909631 TI - Enteric disease in rabbits inoculated with stool filtrates from persons with chronic diarrhea. PMID- 2909632 TI - Diarrhea and Campylobacter infections in patients infected with the human immunodeficiency virus. PMID- 2909633 TI - Immunogenicity of a candidate live oral typhoid/cholera hybrid vaccine in humans. PMID- 2909634 TI - Genotypes of the group-specific component protein in black intravenous drug abusers. PMID- 2909635 TI - The incidence of bacteremia after skin surgery. PMID- 2909636 TI - Cutaneous infection caused by Flavobacterium meningosepticum. PMID- 2909637 TI - Deferoxamine treatment as a risk factor for zygomycete infection. PMID- 2909638 TI - A case report of Anaerobiospirillum causing septicemia. PMID- 2909639 TI - A histopathologic study of cerebral malaria in a rhesus monkey model. PMID- 2909640 TI - Penicillin-binding protein families: evidence for the clonal nature of penicillin resistance in clinical isolates of pneumococci. AB - In view of the worldwide emergence of penicillin-resistant pneumococci among clinical isolates it was of importance to examine a large number of strains to test the uniformity of the resistance mechanism. Among 160 clinical isolates of pneumococci (minimum inhibitory concentration [MIC], 0.005-16 micrograms/mL), susceptible strains showed a common pattern of five penicillin-binding proteins (PBPs) with high penicillin affinities (PBP 3 greater than 1A greater than or equal to 2A greater than 1B greater than 2B). PBPs 1A, 2A, and 2B (but not PBP 3) each showed distinct stepwise decreases in penicillin affinities parallel with increasing levels of antibiotic resistance. The number and molecular sizes of PBPs became variable in strains with MIC values greater than 1.0 microgram/mL; among 39 strains with a MIC of greater than or equal to 1.0 microgram/mL, 11 distinct and stable PBP patterns could be identified. Using PBP profiles, serotypes, and antibiotic resistance patterns, as well as data on isolation dates and sites, we identified at least three groups of resistant strains that showed clear indication of clonal origin. PMID- 2909641 TI - Clinical trials of antimicrobial agents following licensure. PMID- 2909642 TI - Enzyme-linked immunosorbent assays for Lyme disease: reactivity of subunits of Borrelia burgdorferi. AB - We prepared fractions of Borrelia burgdorferi, the etiologic agent of Lyme disease, from cultured spirochetes and used them as antigen in an enzyme-linked immunosorbent assay (ELISA) for IgG antibody. Polystyrene plates coated with an extract containing major proteins with apparent molecular masses of 34, 39, 59, and 68 kilodaltons had comparable sensitivity but greater specificity than plates coated with whole cells. Of the 33 serum specimens from individuals with Lyme disease that reacted with whole cells of B. burgdorferi in the class-specific ELISA, 30 (91%) remained positive when this extract was used. Cross-reactivity was minimal with antibody to treponemes. Use of subunit antigens may improve serological diagnosis of Lyme disease. PMID- 2909643 TI - An enzyme-linked immunoelectrotransfer blot assay and glycoprotein antigens for diagnosing human cysticercosis (Taenia solium). AB - An enzyme-linked immunoelectrotransfer blot (EITB) assay was developed for immunodiagnosing human cysticercosis. The assay uses lentil-lectin, affinity purified glycoprotein antigens. A battery of 532 serum and 46 cerebrospinal fluid (CSF) samples (148 cases of parasitologically confirmed cysticercosis, 54 healthy controls, and 18 types of heterologous infections [376 cases]) were used to ascertain the assay's efficacy. All but three of the samples from cases of confirmed cysticercosis were positive; none of the samples from healthy controls or heterologous infections reacted to any of the diagnostic bands. Thus, the assay is 98% sensitive and 100% specific. We identified seven major glycoprotein bands that are commonly recognized by virtually all serum and/or CSF samples from patients with confirmed cysticercosis. There was no significant difference in test performance when CSF was compared with serum. The EITB assay is highly reproducible and simple to perform, and the reagents (including the antigens blotted onto strips) are very stable. PMID- 2909644 TI - Effect of iron loading on transmembrane potential, contraction, and automaticity of rat ventricular muscle cells in culture. AB - The effect of iron loading on membrane potential and cellular contractility was examined in cultured heart cells obtained from newborn rat ventricles exposed to ferric ammonium citrate at iron concentrations of 20, 40, and 80 micrograms/ml for 24 hours. The main functional effect of iron loading was depression of the overshoot potential. Severe arrhythmias were encountered in two of eight studies with 40 micrograms/ml iron and in two of seven studies with 80 micrograms/ml iron, but they were not found in any of the 29 control studies (p less than 0.01). Iron loading also resulted in a significant enhancement of cellular LDH release, indicating a loss of cell membrane integrity. In vitro treatment of iron loaded cells with deferoxamine, a selective iron-chelating compound, resulted in a striking reversal of the iron-induced depression in the plateau phase of action potential, the disappearance of arrhythmias, and a reduction in LDH leakage. These favorable effects of deferoxamine lend support to the contention that the observed abnormalities following iron-loading were specific expressions of iron toxicity. Although these observations are consistent with iron-induced peroxidative damage to membrane lipid components, further studies are required in order to elucidate the nature of such a putative membrane effect of excess iron. PMID- 2909645 TI - Monophosphoryl lipid A blocks the hemodynamic effects of lethal endotoxemia. AB - Monophosphoryl lipid A (MPL) is a "nontoxic" derivative of lipid A. We hypothesized that, because of the structural similarity between MPL and the lipid A portion of lipopolysaccharide (a "toxic" moiety of endotoxin), hemodynamic events occurring during endotoxemia could be attenuated by administration of MPL. Lipopolysaccharide (LPS) from Salmonella minnesota wild type S and MPL from S. minnesota R595 were used for the study. Fifteen Sprague-Dawley rats were randomized to receive either (1) 0.50 mg LPS per 100 gm body weight intravenously, (2) 0.50 mg MPL per 100 gm body weight intravenously, or (3) 0.5 mg MPL per 100 gm body weight intravenously followed in 15 minutes by 0.50 mg LPS per 100 gm body weight intravenously. Arterial pressure, thermodilution cardiac output, and central venous oxygen saturation were measured before and 30 and 60 minutes after LPS administration. In LPS-treated animals, cardiac output decreased from 448 +/- 28 ml/kg/min to 336 +/- 15 ml/kg/min (p less than 0.02), and central venous oxygen saturation decreased from 71% +/- 1% to 62% +/- 2% (p less than 0.05). Mean arterial pressure decreased from 134 +/- 5 mm Hg to 90 +/- 6 mm Hg (p less than 0.01). In MPL-treated and MPL + LPS-treated animals, no significant changes were observed in cardiac output, central venous oxygen saturation, or arterial pressure. These data indicate that MPL is not associated with the adverse cardiovascular responses observed after LPS administration. Furthermore, administration of MPL blocks the development of acute circulatory failure during endotoxemia. PMID- 2909646 TI - Effects of diabetes on myocardial perfusion in the atherosclerotic monkey. AB - We examined the influence of diabetes on the severity of coronary atherosclerosis, as judged by coronary morphometric and blood flow studies. Cynomolgus monkeys were fed a coconut-peanut oil mixture plus cholesterol to induce the plaque lesions of atherosclerosis in nondiabetic (group 2) and diabetic monkeys (group 3). Group 1 consisted of chow-fed controls. After 18 months of hypercholesterolemia, the animals were anesthetized to assess myocardial blood flow, by use of radioactive microspheres. Transmural and inner/outer wall flow ratios were normal in the two lipid-fed groups in the basal state. Vasodilation after adenosine (0.45 mg/kg/min IV) elicited a more than threefold rise of transmural blood flow in group 1, and a significantly reduced increment in groups 2 and 3. The blood flow ratio was not different from unity in group 1 but declined to 0.69 +/- 0.03 in group 2 and 0.69 +/- 0.06 in group 3, with similar decrements of heart rate and aortic pressure. In contrast to results in group 1, left ventricular filling pressure rose and velocity of contractile elements declined to a similar extent in groups 2 and 3 after adenosine, consistent with myocardial ischemia. Morphometric measurements as well as chemical analyses were performed on the three major coronary arteries. The degree of intimal thickening and increase of cholesterol and collagen content were comparable in groups 2 and 3. Thus, in this model the plaque lesions of atherosclerosis did not appear to be intensified by diabetes. Moreover, the responses to adenosine in terms of myocardial underperfusion and mechanical dysfunction were comparable in the two experimental groups. PMID- 2909647 TI - Quantitation of component proteoglycans during long-term organ explant culture of human osteoarthritic hip cartilage. AB - Cartilage from 14 human osteoarthritic femoral heads was studied in vitro 1, 20, and 30 days after explantation to assess component proteoglycans. Newly synthesized proteoglycans labeled with tritiated-leucine or Na(2)35SO4 and existing, hexuronate-containing proteoglycans were eluted on Sepharose CL-2B (0.5 mol/L sodium acetate, pH 5.8) as four subpopulations with average partition coefficients ranging from 0.05 to 0.9. These subpopulations were comprised of proteoglycans aggregated to hyaluronic acid and principally nonaggregated proteoglycans. Although this distribution was stable to day 20, by day 30, 35SO4 labeled proteoglycan aggregate decreased and smaller proteoglycans increased in amount. With longer culture periods, the proteoglycan subpopulations contained fewer high-density proteoglycans, which were also decreased in size. PMID- 2909648 TI - Effects of bile duct ligation and dietary change on hepatic carbohydrate metabolism in rats. AB - Effects of bile duct ligation and dietary change on hepatic carbohydrate metabolism in rats were studied by analyzing the levels of fructose 2,6 bisphosphate (fructose-2,6-P2) and other metabolites. There was no significant difference in the levels of fructose-2,6-P2 and glycolytic intermediates between rats with and without bile duct ligation when rats were in a fed state. However, the levels of fructose-2,6-P2, hexose monophosphates, and triose phosphates increased and the level of plasma glucose decreased in rats with bile duct ligation in a starved state. The crossover analysis of gluconeogenic intermediates in rats with bile duct ligation showed accumulations of hexose monophosphates together with fructose-2,6-P2 in spite of the starved state of rats, indicating an impaired conversion of glucose 6-phosphate to glucose. Despite the activation of the fructose 6-phosphate-fructose 1,6-bisphosphate futile cycle as indicated by these findings, the energy charge levels were not reduced. The block at the level of glucose production may explain the relative predominance of insulin effect on glycolysis. PMID- 2909649 TI - Dietary protein and glomerular response to subtotal nephrectomy in the rat. AB - Renal tubules and glomeruli undergo hypertrophy after partial renal ablation. Glomerular and vascular scarring and progressive renal insufficiency may later occur. In the present studies, we have documented the filtration characteristics of glomeruli isolated from rats that had undergone subtotal nephrectomy and been fed a normal protein (NP) diet (24 gm protein per 100 gm chow) or a protein restricted (PR) diet (6 gm protein per 100 gm chow) and compared these glomeruli to those of sham-operated (SHAM) rats maintained on a normal diet. Body weight of SHAM rats increased by 30% during the 28 weeks of the study. Weight of NP rats did not change significantly, and weight of PR rats decreased by about 25%. Seven weeks after surgery, the glomeruli of NP rats were significantly larger and the ultrafiltration coefficients (Kf) were higher than those of SHAM rats; glomeruli of PR rats were of normal size but also had increased Kf. Twenty-eight weeks after surgery, the glomeruli of rats in each group were larger than at 7 weeks. Kf was no longer elevated in NP rats. Glomerular capillary hydraulic conductivity (Lp) was equal in all groups at 8 days but was increased at 7 weeks and decreased 28 weeks after surgery in NP rats. We hypothesize that glomerular hypertrophy occurs in response to renal ablation and that subsequent changes in the capillary wall lead to diminished Lp. Protein restriction in this model prevents both glomerular hypertrophy and a decrease in Lp. PMID- 2909651 TI - Modification of the oxygen affinity and intracellular hemoglobin concentration of normal and sickle cells by means of an osmotic pulse. AB - Important properties of red blood cells (RBCs), including oxygen affinity and intracellular hemoglobin concentration, may be modified by means of an osmotic pulse. The pulse is developed by rapid dilution of a suspension of RBCs to which dimethylsulfoxide has been added. The nature and degree of RBC modification is dependent on the composition of the diluent solution. The purpose of this investigation was to explore the dependence of these changes on diluent composition and to determine the stability of altered cellular properties with in vitro incubation. For both normal control RBCs (A cells) and RBCs from patients with sickle cell anemia (S cells), cells with increased volume and markedly decreased intracellular hemoglobin concentration (65% to 70% of control) or with normal volume and moderately decreased hemoglobin concentration (80% to 85% of control) were prepared. These modifications were accomplished with hemoglobin yields ranging from 60% to 90%, depending on the diluent used, the cell type, and the intensity of treatment. For the same degree of inositol hexaphosphate (IHP) incorporation into A cells, as shown by the shift in oxygen half-saturation pressure (P50), diluent formulations with constant total osmolality but varying IHP concentration gave the same degree of hemoglobin loss per cell. Posttreatment cell size, however, ranged from slightly smaller than control to approximately 20% larger. On incubation, the larger cells returned toward normal size, whereas those with normal posttreatment size remained constant. S cells showed the same general changes with treatment and incubation but with greater variation. The treated S cells exhibited markedly reduced morphologic sickling on deoxygenation. PMID- 2909650 TI - Application of an erythrocyte aluminum assay in the diagnosis of aluminum associated microcytic anemia in patients undergoing dialysis and response to deferoxamine therapy. AB - A method for measuring erythrocyte aluminum content was developed. Erythrocyte aluminum levels correlated with plasma aluminum concentrations in normal controls and in patients undergoing dialysis (r = 0.90, p less than 0.001). In vitro studies showed that erythrocyte aluminum concentrations were not altered by contamination of blood samples, which is a common problem with plasma determinations. The need for anticoagulation and rapid processing were disadvantages of this assay. In the dialysis population studied, the correlative data between mean cell volume and both plasma and erythrocyte aluminum levels (r = -0.50, p less than 0.001; and r = -0.69, p less than 0.001) and lack of correlation with serum ferritin suggested that aluminum overload and not iron deficiency was the cause of microcytic anemia. Patients undergoing continuous ambulatory peritoneal dialysis had lower plasma and erythrocyte aluminum levels and absence of microcytic anemia compared with patients undergoing hemodialysis. Therapy with deferoxamine in 13 patients with aluminum-related microcytic anemia resulted in a decrease in erythrocyte and plasma aluminum content in all patients (265.5 +/- 69.2 micrograms/L to 22.6 +/- 9.7 micrograms/L and 196 +/- 30 micrograms/L to 129 +/- 13.8 micrograms/L). The relatively smaller decrease in plasma aluminum levels suggested mobilization of aluminum from tissues other than erythrocytes. Aluminum chelation most probably occurred from premature erythrocytes, because in vitro studies showed that deferoxamine was unable to chelate aluminum from mature erythrocytes. Hemoglobin level, hematocrit measurement, and mean cell volume showed significant improvement (p less than 0.001). Ten patients showed normalized mean cell volume after 6.2 +/- 2 months of therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2909652 TI - Disappointment and promise in the pharmacologic treatment of obstructive sleep apnea. PMID- 2909653 TI - A unique insertion in the primary structure of bovine amyloid AA protein. AB - Amyloid fibrils were isolated from kidney tissue of a cow afflicted with renal failure caused by spontaneous reactive amyloidosis. These fibrils were reduced and alkylated, and the amyloid subunit protein was isolated on a column of Sepharose CL6B. The protein was fragmented with both trypsin and Staphylococcus protease, and the resultant peptides were separated by high-performance liquid chromatography. Sequence analysis gave the complete primary structure of the protein with overlaps of the tryptic peptides confirmed by the Staphylococcus protease peptides. Comparison of the bovine amyloid A (AA) amino acid sequence with human protein AA demonstrates complete invariability from human position 33 to 45 and a very high degree of homology from positions 16 to 29 and 46 to 63. These data indicate that these portions of the molecule may be significant factors in amyloid fibrilogenesis. The bovine AA protein shows a blocked amino terminus, as is the case with the dog and the cat AA proteins. In addition, this protein contains an insertion of nine amino acid residues between human positions 69 and 70. The existence of an additional six residues after position 76 makes the bovine AA an unusually large 90 amino acid peptide. These findings point to a high tolerance for mutation in the carboxyl end of the molecule. PMID- 2909654 TI - Sensitivity and predictive value of serum ferritin and free erythrocyte protoporphyrin for iron deficiency. AB - The sensitivity and predictive value of serum ferritin (SF) and free erythrocyte protoporphyrin (FEP) for iron deficiency (ID) was evaluated by studying 272 subjects with uncomplicated ID (174 with anemia and 98 without) in whom diagnosis was confirmed by the response to iron supplementation. Overall, the sensitivity, at 95% specificity, was 82% (79% in women, 94% in men) for SF and 61% (60% in women, 65% in men) for FEP. The sensitivity varied as a function of hemoglobin values, dropping from over 90% for both tests in the case of severe anemia, to approximately 70% for SF and less than 50% for FEP in the absence of anemia. The predictive value decreases more sharply for FEP than for SF with increasing hemoglobin levels. It is concluded that SF is preferable to FEP for the detection of ID, particularly in the absence of anemia. However, owing to the unsatisfactory predictive value at low prevalence, SF should be used as a screening test for ID without anemia only when the prevalence is at least 20%. PMID- 2909655 TI - Effect of salicylate on upper airway stability and pressure flow: relationship in anesthetized dogs. AB - Previous studies have shown that upper airway muscle activity is augmented in response to increased respiratory drive, thereby improving upper airway patency. In the present study we evaluated the effect of salicylate, a well-known respiratory stimulant, on upper airway stability and pressure-flow relationship. Multiple levels of airflow were used to assess pressure-flow relationship in the isolated airways of anesthetized dogs and to calculate the coefficients of Rohrer's equation P = K1V + K2V2. In addition, we measured the negative intraluminal pressure needed to collapse the upper airway. These measurements were repeated after intravenous administration of sodium salicylate, 250 mg/kg. Salicylate-induced hyperventilation was associated with increased alae nasi electrical activity. Resistance to airflow and K2 decreased significantly (p less than 0.01), suggesting dilation of the upper airway lumen. The intraluminal pressure under which upper airway collapse occurred became more negative in all dogs (from -5.0 +/- 0.8 to -8.5 +/- 1.3 cm H2O, p less than 0.01), indicating improved stability of the upper airway walls. These findings suggest that salicylate, and presumably other pharmacologic agents that stimulate ventilation, can improve both upper airway patency and upper airway stability. PMID- 2909657 TI - Role of the thymus in natural tolerance to an autologous protein antigen. AB - C5-deficient mice grafted with thymus from C5-sufficient donors and immunized with C5 failed to make humoral antibody to C5, suggesting that the transfer of thymus had induced tolerance. Irradiated C5-deficient hosts repopulated with lymphoid cells from thymectomized C5-deficient mice grafted with C5-sufficient thymus also failed to respond to immunization with C5, thus showing that the state of tolerance can be adoptively transferred. These results demonstrate that natural tolerance to self-protein antigen is "learned" in the thymus. PMID- 2909656 TI - A human serum mannose-binding protein inhibits in vitro infection by the human immunodeficiency virus. AB - In vitro infection by the human immunodeficiency virus (HIV) of CD4+ H9 lymphoblasts is inhibited by a mannose-binding protein (MBP) purified from human serum. In addition, MBP is able to selectively bind to HIV-infected H9 cells and HIV-infected cells from the monocyte cell line U937. These results indicate MBP most likely recognizes high mannose glycans known to be present on gp120 in the domain that is recognized by CD4 and thereby inhibits viral entry to susceptible cells. In support of this contention, recombinant gp120 binds directly to MBP; the binding is saturable, mannan inhibitable, removed by N-glycanase treatment, and dependent on divalent cations. PMID- 2909658 TI - Active and latent forms of transforming growth factor beta activity in synovial effusions. AB - We have evaluated the possible involvement of TGF-beta in rheumatoid arthritis by assay of 16 cell-free synovial fluids for the presence of its active and "latent" forms. Evidence has been obtained for TGF-beta-like activity in synovial effusions by four criteria: (a) TGF-beta receptor competition, (b) soft-agar colony formation of AKR-2B and NRK-49F indicator cells, (c) immunological neutralization of the biological activity, and (d) biochemical activation of a latent form. PMID- 2909659 TI - Evidence for a primary association of celiac disease to a particular HLA-DQ alpha/beta heterodimer. AB - Typing of DNA from 94 unrelated children with celiac disease (CD) with HLA-DQA1 and -DQB1 allele-specific oligonucleotide probes revealed that all but one (i.e., 98.9%) may share a particular combination of a DQA1 and a DQB1 gene. These genes are arranged in cis position on the DR3DQw2 haplotype and in trans position in DR5DQw7/DR7DQw2 heterozygous individuals. Thus, most CD patients may share the same cis- or trans-encoded HLA-DQ alpha/beta heterodimer. PMID- 2909660 TI - The low turning point. A control mechanism in the course of mental disorder. AB - Recent research has suggested that persons with severe mental disorders may have psychological control mechanisms that influence the course of their disorders. One mechanism that appears to be particularly significant is the low turning point. Based on data obtained as part of an intensive follow-along study, the low turning point process is described in this report. It is identified as involving three phases: a) an initial rigid focus on one coping mechanism for dealing with stress; b) relinquishing of that focus and decompensation; and c) reorganizing one's life more broadly. The functioning that emerges from this experience often appears to be more adaptive than that existing before its onset. Conceptual implications of this process are discussed. PMID- 2909661 TI - Early discontinuance of borderline patients from psychotherapy. AB - Sixty newly hospitalized patients with borderline personality disorder who began psychotherapy were followed for 6 months. Thirty-six discontinued their therapy- most often (N = 26) this was due to covert opposition, familial resistance, or angry dissatisfaction with treatment. The dropouts were healthier on some baseline measures than those who continued in therapy. Clinical implications that may diminish dropouts are discussed. PMID- 2909662 TI - Metamemory perceptions in depressions of young and older adults. AB - This research investigated how depression in two age groups related to responses on a metamemory questionnaire (MMQ), and to the correspondence between MMQ self reports and performance on memory tests. Forty-four younger and 56 older women were clinically assessed and completed both the MMQ and a series of experimental memory procedures. Data on 11 MMQ subscales were analyzed by analysis of variance, chi 2, and canonical correlation techniques. Compared with controls, depressed subjects tended to report more generalized and extensive memory difficulties, particularly in recent as opposed to remote memory, but were not deficient in basic metamemory knowledge and did not manifest different perceptions regarding age changes in memory or regarding its personal significance. There was no evidence for a differential impact of late-life depression on metamemory perceptions, reflected by the general absence of age-by depression interactions. Cumulatively, self-reports correlated .598 with objective measures, a relationship that did not vary as a function of age or depression. Reports about the retention of "important" information and about the use of recall strategies were identified as the only self-report measures reliably associated with performance. PMID- 2909663 TI - A pharmacokinetic study of high-dose continuous infusion cisplatin in children with solid tumors. AB - The pharmacokinetics of cisplatin were investigated in 14 patients, aged 10 months through 13 years who were affected by solid malignant tumors. High-dose cisplatin (40 mg/m2/d) was administered with repeated courses for five days as a continuous intravenous (IV) infusion. Total platinum (Pt) levels in plasma and urine and free (protein-unbound) Pt levels in plasma ultrafiltrate were determined by inductively coupled plasma atomic emission spectrometry (ICP-AES). Areas under the concentration v time curve (AUCs) for mean total and free Pt levels were calculated for the 120-hour period of infusion and for the 384 and 120 hours following its completion, respectively. Half-lives of total and free Pt in plasma were calculated for the 216 hours following completion of infusion in five patients at their first course. The fraction of the administered Pt dose excreted in urine as Pt was determined for the five-day period of infusion and seven-day period after its completion. A total of 36 courses were studied. Maximum average Pt levels were reached after 120 hours of infusion: at the first course, 3.22 and 0.17 micrograms/mL for total and free Pt, respectively. Platinum levels declined according to a biexponential model, with initial half-lives of 18.3 and 16.9 minutes, and terminal half-lives of 81.9 and 59.0 hours as determined for total and free Pt, respectively. In the second and third courses studied there was a progressive increase in mean Pt plasma levels. Consequently, the free drug exposure as measured by AUC increased in all patients with repeated courses: 47.7% for the second and 124.4% for the third course, when compared with the first. At the same time, the mean fraction of the dose excreted in the urine for the 12-day period considered, was 44.1% for the first course, 36.2% for the second, and 28.4% for the third. The progressive enhancement of tissue exposure to the free cytotoxic drug, resulting from a reduced renal clearance of Pt with sequential courses of cisplatin, produced mainly increased toxicity while therapeutic effect progressively diminished. PMID- 2909664 TI - Early responder myeloma: kinetic studies identify a patient subgroup characterized by very poor prognosis. AB - In order to assess the prognostic value of rapid tumor mass reduction in responding multiple myeloma (MM) patients, 100 consecutive patients were analyzed, and bone marrow plasma cell kinetic characteristics were evaluated at diagnosis. Forty-two patients obtained a tumor mass reduction greater than or equal to 50% with three cycles of chemotherapy and within 3 months (early responder myeloma [ERM]), and 23 in greater than 3 months (slow responder myeloma [SRM]). Survival rates in these two groups were not statistically different (P = .07). The labeling index (LI) of bone marrow plasma cells was significantly higher in ERM patients than in SRM patients (1.8 +/- 2.0 v 0.8 +/- 0.7, P = .006). The LI was used to separate the ERM patients into two well-defined subgroups. ERM patients with a LI greater than or equal to 2% showed a median survival of 16.4 months, whereas ERM patients with a LI less than 2% did not reach the median survival at 46.9 months (P less than .0044). Remission duration was also significantly different: 12.2 months in the high LI subgroup and 26.3 months in the low LI subgroup (P less than .0025). Early response itself does not correspond to shorter remission duration and shorter survival, but it is a poor prognostic factor if associated with a high plasma cell proliferative activity. PMID- 2909665 TI - The use of bone marrow aspirations and lumbar punctures at the time of diagnosis of retinoblastoma. AB - Lumbar punctures (n = 115) and bone marrow aspirations (n = 114) were performed as part of the routine initial diagnostic evaluation of 115 children with retinoblastoma. Three spinal fluid examinations were positive for tumor cells, and bone marrow smears of three children demonstrated clumps of tumor cells. Five of the six positive studies were in patients with stage IV (extraglobar) disease. These results show that demonstrable CSF or bone marrow involvement is so infrequent an event at diagnosis in patients without symptoms, signs, or histologic evidence of tumor dissemination (stages I-II) as to support a recommendation that these studies need not be performed routinely in such patients. If, after enucleation, there is evidence of extraglobar extension, or if patients have symptoms or signs of CNS or systemic spread (stages III or IV), both procedures should be performed to accurately stage disease and provide baseline measurements of tumor involvement for monitoring of response to chemotherapy and/or irradiation. These results have importance in terms of justification of invasive work-up of most (greater than 85%) affected children, and cost containment. PMID- 2909666 TI - Residual mass and gallium scanning. PMID- 2909667 TI - Leukemia risk following radiotherapy for breast cancer. AB - To evaluate further the relationship between high-dose radiotherapy and leukemia incidence, a nested case-control study was conducted in a cohort of 22,753 women who were 18-month survivors of invasive breast cancer diagnosed from 1935 to 1972. Women treated for breast cancer after 1973 were excluded to minimize the possible confounding influence of treatment with chemotherapeutic agents. The cases had histologically confirmed leukemia reported to the Connecticut Tumor Registry (CTR) between 1935 and 1984. A total of 48 cases of leukemia following breast cancer were included in the study. Two controls were individually matched to each leukemia case on the basis of age, calendar year when diagnosed with breast cancer, and survival time. Leukemia diagnoses were verified by one hematologist. Radiation dose to active bone marrow was estimated by medical physicists on the basis of the original radiotherapy records of study subjects. Local radiation doses to each of the 16 bone marrow components for each patient were reconstructed; the dose averaged over the entire body was 530 rad (5.3 Gy). Based on this dosage and assuming a linear relationship between dose and affect, a relative risk (RR) in excess of 10 would have been expected. However, there was little evidence that radiotherapy increased the overall risk of leukemia (RR = 1.16; 90% confidence interval [CI], 0.6 to 2.1). The risk of chronic lymphocytic leukemia, one of the few malignancies without evidence for an association with ionizing radiation, was not significantly increased (RR = 1.8; n = 10); nor was the risk for all other forms of leukemia (RR = 1.0; n = 38). There was no indication that risk varied over categories of radiation dose. These data exclude an association between leukemia and radiotherapy for breast cancer of 2.2-fold with 90% confidence, and provide further evidence that cell death predominates over cell transformation when high radiation doses are delivered to limited volumes of tissue. PMID- 2909668 TI - Estimating the risk of second primary tumors following cancer treatment. PMID- 2909670 TI - Axon regeneration through blood vessel allografts after cyclosporine treatment. AB - The present study describes the usefulness of blood vessel allografts to repair gaps in rat peripheral nerve after immunosuppression with cyclosporine. Isogeneic strains of rats with known histoincompatibility were used for this study. A 10-mm gap was created in the peroneal nerve of host Fischer rats. The gap was bridged by a 12-mm section of internal carotid artery removed from a Buffalo strain of rat. The host rats were divided into two groups. One group received no immunosuppression, whereas the other group was treated with cyclosporine. Untreated control rats immunologically rejected the allografted vessels and were unable to support host axonal regeneration through them. On the other hand, in cyclosporine-treated rats the allografted vessels survived. The regenerating host axons reorganized to form a functional nerve within the vessel conduit. The regenerated axons persisted even after rejection of the allografted vessel caused by cessation of immunotherapy. These results show that blood vessel allografts can serve as an effective conduit for reorganization of regenerated nerves and can bridge gaps in peripheral nerves. PMID- 2909669 TI - Prognostic indicators of laparotomy findings in clinical stage I-II supradiaphragmatic Hodgkin's disease. AB - Between July 1968 and July 1986, 915 patients with clinical stage (CS) I and II Hodgkin's disease limited to sites above the diaphragm underwent laparotomy and splenectomy at Stanford University. Fifteen percent were CS I, of whom 76% had cervical/supraclavicular disease, 13% axillary disease, and 9% mediastinal presentations. CS I patients were more likely to be male, were significantly older, and were significantly less likely to have nodular sclerosis (NS) histology than CS II patients. Twenty percent of CS I patients and 30% of CS II patients were pathologically upstaged. No CS I patients were upstaged to pathological stage (PS) IV. Univariate and multivariate analyses of presenting clinical characteristics were performed to predict staging laparotomy findings. CS I women, CS I patients with mediastinal-only disease, and CS I men with either lymphocyte predominance or interfollicular histologies were at low risk for having disease below the diaphragm (5%) or requiring chemotherapy (0%). CS II women who were less than 27 years old and had only two or three sites of disease were also at low risk for upstaging (9%) or requiring chemotherapy (2%). Mixed cellularity histology and male gender were associated with increased risk for subdiaphragmatic disease and require laparotomy; the presence of systemic symptoms was not correlated with laparotomy findings. These results confirm the importance of performing staging laparotomy for the majority of patients who present with supradiaphragmatic Hodgkin's disease if treatment programs are based on the presence and extent of subdiaphragmatic disease. Selected subgroups are at low risk for subdiaphragmatic disease and might be spared laparotomy if they are treated with mantle, paraaortic, and splenic irradiation. PMID- 2909671 TI - Synovial chondromatosis of the temporomandibular joint with intracranial extension. Case report. AB - The authors report the unusual presentation of an intracranial extension of synovial chondromatosis of the temporomandibular joint. The patient presented with a peripheral facial nerve paralysis and anacusis. Computerized tomography revealed the lesion, but fine-needle biopsy was inconclusive. Craniotomy with removal of the tumor was performed, and pathological studies confirmed the diagnosis. The facial nerve dysfunction was thought to be secondary to direct neural compression. PMID- 2909672 TI - Foramen magnum decompression in an infant with homozygous achondroplasia. Case report. AB - Homozygous achondroplasia is a rare yet distinct clinical entity. Most infants succumb to an early death as a result of respiratory compromise due to upper airway obstruction, thoracic cage deformity, and/or cervicomedullary compression. The successful cervicomedullary decompression of a 16-week-old infant with homozygous achondroplasia is described. This report suggests that homozygous achondroplasia is not universally fatal and that these infants are potentially viable if managed by aggressive respiratory and surgical measures. PMID- 2909673 TI - Atlanto-axial rotational limitation secondary to osteoid osteoma of the axis. Case report. AB - An unusual case of atlanto-axial rotational limitation secondary to an osteoid osteoma of the axis is presented. Transoral microsurgical resection followed by physical therapy improved the clinical symptoms. This case illustrates several unique problems within the cervical spine as well as the efficacy of the transoral approach to the axis. PMID- 2909674 TI - Magnetic resonance imaging of vascular compression in trigeminal neuralgia. Case report. AB - A case of trigeminal neuralgia is reported in which preoperative high-resolution magnetic resonance imaging demonstrated vascular compression of the trigeminal nerve. Surgery confirmed compression and indentation of the fifth nerve by a large branch of the superior cerebellar artery. Following microvascular decompression, the patient experienced no further pain. Magnetic resonance imaging may be useful in the evaluation of trigeminal neuralgia to identify a subgroup of patients who could benefit most from decompression. PMID- 2909675 TI - Preoperative diagnosis of Lhermitte-Duclos disease by magnetic resonance imaging. Case report. AB - Lhermitte-Duclos disease is a benign, presumably hamartomatous lesion of the cerebellum which presents clinically as a mass lesion. Pathologically, it consists of thickening of both the molecular and granular cell layers of the cerebral cortex which enlarges the folia but allows for preservation of the gyral pattern of the cerebellar cortex. Preoperative diagnosis with computerized tomography and other studies has not been possible, and even at surgery the diagnosis may be missed because of the preservation of the gyral pattern. The sensitivity of magnetic resonance imaging allows recognition of the cortical nature of the mass lesion, and especially the gyral pattern within the mass lesion, providing a diagnostic image which is unlikely to be confused with any other pathological process in the cerebellum. Preoperative diagnosis of Lhermitte Duclos disease allows surgeons to plan an appropriate decompressive procedure. PMID- 2909676 TI - Thermosensitive determination of patency in lumboperitoneal shunts. Technical note. AB - Surface cooling and thermistor recording over shunt tubing was used in 23 studies of cerebrospinal fluid shunt patency in 19 patients with lumboperitoneal shunts and normal-pressure hydrocephalus. Shunt patency was shown by downward reflection of the recording trace similar to that obtained for ventriculoperitoneal shunts. Obstruction was demonstrated by a flat-line recording or an upward deflection. PMID- 2909677 TI - Prophylactic parenteral antibiotics in neurosurgery. PMID- 2909678 TI - EKG artifacts during intraoperative evoked potential monitoring. PMID- 2909679 TI - Treatment of carotid sinus hypersensitivity. PMID- 2909680 TI - Treatment of oligodendrogliomas. PMID- 2909681 TI - MR imaging of subarachnoid hemorrhage. PMID- 2909682 TI - Cerebral blood flow response to acetazolamide. PMID- 2909683 TI - Hemangioblastomas of the central nervous system. A 10-year study with special reference to von Hippel-Lindau syndrome. AB - The findings of a 10-year study (1976 to 1986) conducted in southwest Germany on hemangioblastomas (HBL's) of the central nervous system (CNS) are presented. During that period, 47 HBL's were diagnosed and surgically removed in 44 patients, with a good postoperative survival rate and prognosis. The majority (83%) of these tumors were located in the cerebellum. By thorough clinical examination of the patients and careful evaluation of their family background, it was found that 23% of the HBL patients were afflicted with von Hippel-Lindau syndrome. In addition to the CNS tumors, 14 neoplastic or similar lesions were detected in other tissues. These included angiomatosis of the retinae, pheochromocytomas, pancreatic cysts, renal cysts, and renal carcinoma. The diagnosis of von Hippel-Lindau syndrome was thus established in seven families. The authors suggest the need for a screening program for patients with HBL of the CNS which is designed to confirm or exclude ocular or visceral lesions associated with von Hippel-Lindau syndrome. PMID- 2909684 TI - Lack of histopathological correlation of malignant ependymomas with postoperative survival. AB - It is widely believed that an important determinant of clinical behavior and prognosis in patients harboring an ependymoma is the histological grade of malignancy of the tumor. Excluding from the present analysis examples of ependymoblastoma (a highly cellular, embryonal tumor occurring in children, with a notably poor prognosis and a tendency to subarachnoid spread), an attempt was made to correlate 15 cases of histologically malignant ependymoma with clinical recurrence and postoperative patient survival times. Ten patients (67%) were alive from 15 months to 14 years after surgery (median survival time 8.8 years); one patient had a histologically benign recurrence 11 years after surgical resection. Five patients (33%) died from a local recurrence of their tumor; their postoperative survival times ranged from 13 months to 6 years (median 2.5 years). The prognosis of malignant ependymomas is therefore highly variable. No correlation was possible between the tumor's histological features, site, or likelihood of recurrence. This lack of clinicohistopathological concordance contrasts with the known correlations that exist in astrocytomas. PMID- 2909685 TI - Primary optic nerve sheath meningiomas. Report of nine cases. AB - Between 1979 and 1987 the authors treated nine cases of primary optic nerve sheath meningioma. The definitive treatment for these lesions is surgical resection, although no single best plan for optimal management has been determined. The data indicate that only small anterior tumors may be removed with preservation of useful vision. With posterior circumferential tumors, there have been no cases of tumor removal with preservation of vision. A management strategy directed toward preservation of vision is discussed. PMID- 2909686 TI - Multiple intracranial meningiomas. AB - The authors report 14 cases of multiple intracranial meningiomas representing 1.1% of all meningiomas operated on at their hospital in the past 35 years. Differentiation of multiple meningiomas, especially from meningiomatosis, must be strict. Since the introduction of computerized tomography scanning, the frequency of these cases has risen from 0.58% to 4.5% in the authors' meningioma series. Despite the multiplicity of sites, multiple meningiomas do not differ in prognosis from benign solitary meningiomas. PMID- 2909687 TI - Neurosurgical management of acute atlas-axis combination fractures. A review of 25 cases. AB - Combination atlas-axis fractures occur relatively frequently and have a higher incidence of neurological morbidity than isolated C-1 or isolated C-2 injuries. Patients with combination C1-2 fracture-subluxation injuries should be studied with thin-section computerized tomography. Appropriate treatment is determined by the type of axis fracture present and includes surgical and nonsurgical strategies. An experience with 25 patients with combination C1-2 fractures is presented, and management and follow-up guidelines are reviewed. PMID- 2909688 TI - Malignant astrocytomas of the spinal cord. AB - The authors review their experience with the operative management of 19 consecutive cases of malignant astrocytoma of the spinal cord. There was a male to female ratio of 1.1:1, and the median age of the population was 14 years (range 1 to 32 years). The median duration of symptoms prior to definitive diagnosis was 7 weeks. Radical excision was carried out in all cases, with 18 patients (95%) receiving radiotherapy and 10 patients (53%) receiving chemotherapy as well. To date, 15 (79%) of the 19 patients in this series have died, with a median survival period of 6 months following surgery. No patient improved after operation. Hydrocephalus was present in 11 patients (58%), seven of whom underwent ventricular shunting procedures. Dissemination of disease was found in 11 patients (58%). Extraneural metastases did not occur in the absence of a ventricular shunt. The authors conclude that malignant astrocytomas of the spinal cord are heralded by a short history followed by rapid neurological deterioration and usually death. The rationale for operation is discussed, and an aggressive approach utilizing adjuvant therapy directed at the entire neuraxis is suggested. PMID- 2909689 TI - Timing of operation for ruptured supratentorial aneurysms: a prospective randomized study. AB - A total of 216 patients with a ruptured aneurysm of the anterior part of the circle of Willis were enrolled into this prospective randomized study of timing of the operation after aneurysmal subarachnoid hemorrhage (SAH). Only patients in clinical Grades I to III (according to the classification of Hunt and Hess) who were admitted and randomly assigned to a treatment group within 72 hours after the SAH were included in the trial. The patients were randomly assigned to one of three operation groups: acute surgery (AS: 0 to 3 days after the SAH; day of SAH = Day 0), intermediate surgery (IS: 4 to 7 days after the SAH), or late surgery (LS: 8 days to an indefinite time after the SAH). Three patients (4.3%) in the IS group and six patients (8.6%) in the LS group died before surgery was undertaken. At 3 months post-SAH, 65 patients (91.5%) from the AS group were classified as independent compared to 55 (78.6%) from the IS group and 56 (80.0%) from the LS group. The management mortality rate in the AS group was 5.6% compared to 12.9% in the LS group. Of the 216 patients enrolled in the timing study, 159 were randomly assigned to an independent double-blind placebo-controlled trial of nimodipine in Grade I to III patients. A total of 79 patients received nimodipine and 80 placebo. When the nimodipine group and the no-nimodipine group (the 80 placebo-treated patients plus the 52 patients who were not entered into the nimodipine trial) were analyzed separately, a significant difference was seen in the outcome of the no-nimodipine group (dependent AS vs. dependent IS, p = 0.01). Nimodipine treatment was associated with a significant reduction of delayed ischemic deterioration (all operation group combined, nimodipine vs. no nimodipine p = 0.01; LS with nimodipine vs. LS with no nimodipine, p = 0.03). PMID- 2909690 TI - Nonhyperemic blood flow restoration and brain edema in experimental focal cerebral ischemia. AB - The effect of suppression of postischemic reactive hyperemia on the blood-brain barrier (BBB) and ischemic brain edema after temporary focal cerebral ischemia was studied in cats under ketamine and alpha-chloralose anesthesia. Regional cerebral blood flow (rCBF) was measured by a thermal diffusion method and a hydrogen clearance method. The animals were separated into three groups. In Group A, the left middle cerebral artery (MCA) was occluded for 6 hours. In Group B, the MCA was occluded for 3 hours and then reperfused for 3 hours; postischemic hyperemia was suppressed to the preischemic level by regulating the degree of MCA constriction. In Group C, the MCA was occluded for 3 hours and reperfused for 3 hours without suppressing the postischemic reactive hyperemia. The brain was removed and cut coronally at the site of rCBF measurement. The degree of ischemic edema was assessed by gravimetry in samples taken from the coronal section and correlated with the degree of BBB disruption at the corresponding sites, evaluated by densitometric determination of Evans blue discoloration. The findings showed that 1) ischemic edema was significantly exacerbated by postischemic hyperemia during reperfusion in parallel with the degree of BBB opening to serum proteins, and 2) suppression of postischemic hyperemia significantly reduced the exacerbation of ischemic edema and BBB opening. These findings indicate that blood flow may be restored without significant exacerbation of postischemic edema by the suppression of postischemic hyperemia in focal cerebral ischemia. PMID- 2909691 TI - Tumor-infiltrating lymphocytes and histocompatibility antigens in primary intracranial germinomas. AB - Subpopulations of tumor-infiltrating lymphocytes (TIL's) and the major histocompatibility complex (MHC) antigens of neoplastic cells were examined in three intracranial germinomas by an immunohistochemical method using monoclonal antibodies. About 70% to 80% of TIL's were T lymphocytes which were either infiltrating diffusely or in clusters, whereas 20% to 30% of TIL's were B lymphocytes which tend to cluster in tumor tissues. Examination of T lymphocyte phenotypes revealed both the cytotoxic/suppressor and helper/inducer T lymphocytes, as in other tumors. However, the existence of a considerable number of B lymphocytes in the TIL population was uncommon and seemed to be a characteristic feature of the intracranial germinoma, which might suggest a difference of host immune response to this neoplasm as compared to other tumors. On examination of the MHC antigens, no MHC class I or II antigens in the neoplastic cells were stained, while positive staining for both antigens was seen in the TIL and stroma tissues. From these findings, it was suggested that the degree of TIL infiltration might not be correlated with the expression of MHC antigens in neoplastic cells in cases of primary intracranial germinoma. PMID- 2909692 TI - Effect of lidocaine after experimental cerebral ischemia induced by air embolism. AB - To investigate possible approaches to the treatment of neural damage induced by air embolism and other forms of acute cerebral ischemia, somatosensory evoked potentials (SEP's) were measured after cerebral air embolism in the anesthetized cat. Air was introduced into the carotid artery in increments of 0.08 ml until the SEP amplitude was reduced to approximately 10% or less of baseline values. Either a saline or lidocaine infusion was begun 5 minutes after inducing cerebral ischemia. In the saline-treated group, SEP amplitude was reduced to 6.7% +/- 1.6% (mean +/- standard error of the mean) of baseline, with a return to 32.6% +/- 4.7% of baseline over a 2-hour period. In the lidocaine-treated group, SEP amplitude was reduced to 5.9% +/- 1.5%, with a return to 77.3% +/- 6.2% over a 2 hour period. The results suggest that lidocaine administration facilitates the return of neural function after acute cerebral ischemia induced by air embolism. PMID- 2909693 TI - Prolonged use of an implantable central venous access system in a child with severe hemophilia. PMID- 2909694 TI - Cat-scratch disease without adenopathy. PMID- 2909695 TI - Congenital muscular dystrophy and epidermolysis bullosa simplex. PMID- 2909696 TI - Comparison of dynamic and static measurements of respiratory mechanics in infants. AB - The objective of this study was to compare the conventional method of measuring respiratory mechanics, which requires the passage of an esophageal tube, with the occlusion technique, which is less invasive. Thirty-nine preterm infants who received mechanical ventilation on the first day were studied before discharge (mean +/- SD: postnatal age 67 +/- 23 days; weight 1790 +/- 300 gm), and 27 of them again at 1 year (weight 8.1 +/- 1.4 kg). Flows were measured through a nosepiece by pneumotachometry, tidal volume by integration of flow, esophageal pressure through a water-filled tube, and airway pressure directly at the nasal piece. Airway occlusion was performed at the end of inspiration, and the following relaxed exhalation was analyzed to give compliance (Crs) and resistance (Rrs) of the respiratory system. These values were compared with dynamic lung compliance (Cdyn) and expiratory resistance (Re) of the previous unoccluded breath. In the younger infants, dynamic and static measurements did not differ significantly and were well correlated (Cdyn/Crs, r = 0.91; Re/Rrs, r = 0.95). In the older infants, Crs was 80% of Cdyn (p less than 0.001), and Rrs was 24% higher than Re (p less than 0.001). The measurements were well correlated (Cdyn/Crs, r = 0.94; Re/Rrs, r = 0.91). The regression line Cdyn versus Crs had a slope (0.77) significantly less than 1; the regression Re versus Rrs had an intercept (13.8) significantly greater than zero. The lower Crs and higher Rrs values can be expected because the static determinations include the chest wall. In the more immature infants, the very compliant chest wall, in combination with an underestimation of Cdyn because of the higher breathing frequency of these infants, may obscure this difference. We conclude that the occlusion technique gives accurate and reproducible results, is easily applied, does not need the passage of an esophageal tube, and is well tolerated by the infants. PMID- 2909697 TI - Efficacy of fluorescent daylight, blue, and green lamps in the management of nonhemolytic hyperbilirubinemia. AB - The efficacy of fluorescent daylight, green, and blue lamps in reducing bilirubin levels was compared in two groups of infants with nonhemolytic hyperbilirubinemia: healthy infants in a term nursery and infants in an intensive care unit. The decline of serum bilirubin concentration was most rapid with the blue lamps, with the duration of exposure required being significantly shorter than that with the other two types of light in both groups. The rate of decline over the first 24 hours, as well as the overall rate of decline for the whole duration of phototherapy, was also significantly greater with the blue lamps, the rate being about twice that for the green lamps in the infants in the intensive care unit; the daylight lamps were intermediate in efficacy. The daylight lamps permitted easy clinical monitoring with minimal side effects, whereas the green and blue lamps were equally disturbing to the attending personnel. The green lamps caused severe erythema and tanning in the initial 200 hours of phototherapy. It appears preferable to use either daylight lamps, which permit enhanced clinical monitoring with adequate efficacy, or special blue lamps, which provide maximal therapeutic effect, rather than green lamps, which offer neither. PMID- 2909698 TI - Commentary on adolescent acquired immunodeficiency syndrome: the next wave of the human immunodeficiency virus epidemic? PMID- 2909699 TI - Evaluation of a testicular cancer curriculum for adolescents. PMID- 2909700 TI - Three-month-old infant with diarrhea, fever, and rash. PMID- 2909701 TI - Changing characteristics of childhood anemia. PMID- 2909702 TI - Query regarding biostatistical questionnaire. PMID- 2909703 TI - Withholding nutrition from newborn infants. PMID- 2909704 TI - Definition of perinatal asphyxia. PMID- 2909705 TI - Postnatal alteration in hematocrit and viscosity in normal infants and in those with polycythemia. PMID- 2909706 TI - Significance of opacification of the maxillary and ethmoid sinuses in infants. AB - To evaluate the incidence and significance of radiographic sinus opacification in infants, we performed computed tomography (CT) of the maxillary and ethmoid sinuses in conjunction with routine cranial CT in 100 infants from birth to 12 months of age. CT was performed for indications other than sinusitis. Prospective concurrent clinical history was obtained and physical examination of the upper respiratory tract was performed. Of 100 infants, 16 had hypoplasia of the maxillary sinuses; 81% (13/16) of these were less than 2 months of age. The antra showed progressive increase in size during the first year of life. Of the 100 infants, 70 had CT sinus opacification, including 67% of those without historical or physical evidence of upper respiratory tract infection. There was a positive correlation of CT findings between the maxillary and ethmoid sinuses in 80% of the infants older than 2 months of age but in only 49% of the younger infants. Radiographic sinus opacification in infants is of uncertain significance and is not diagnostic of upper respiratory tract infection, much less of sinusitis. PMID- 2909707 TI - Oligoantigenic diet treatment of children with epilepsy and migraine. AB - We studied the role of oligoantigenic diets in 63 children with epilepsy; 45 children had epilepsy with migraine, hyperkinetic behavior, or both, and 18 had epilepsy alone. Of the 45 children who had epilepsy with recurrent headaches, abdominal symptoms, or hyperkinetic behavior, 25 ceased to have seizures and 11 had fewer seizures during diet therapy. Headaches, abdominal pains, and hyperkinetic behavior ceased in all those whose seizures ceased, and in some of those whose seizures did not cease. Foods provoking symptoms were identified by systematic reintroduction of foods, one by one; symptoms recurred with 42 foods, and seizures recurred with 31; most children reacted to several foods. Of 24 children with generalized epilepsy, 18 recovered or improved (including 4 of 7 with myoclonic seizures and all with petit mal), as did 18 of 21 children with partial epilepsy. In double-blind, placebo-controlled provocation studies, symptoms recurred in 15 of 16 children, including seizures in eight; none recurred when placebo was given. Eighteen other children, who had epilepsy alone, were similarly treated with an oligoantigenic diet; none improved. PMID- 2909708 TI - Thyroid hormone metabolism and level of illness severity in pediatric cardiac surgery patients. AB - To define better the temporal relationship between alterations in thyroid hormone metabolism and changes in illness severity, we studied thyroid function in 12 children preoperatively and at 2, 12, 24, 48, and 72 hours after cardiac surgery. We then compared these findings with illness severity as assessed by a modification of the Therapeutic Intervention Scoring System (TISS). All patients had significant (p less than 0.01) reduction in serum T3 (mean 35% of baseline levels) and elevation in serum rT3 (mean 237% of baseline levels) in the postoperative period. Average correlation coefficients for the combined data were as follows: TISS and T3 levels, -0.63 +/- 0.17; TISS and rT3 levels, 0.51 +/- 0.18. Examination of individual patient data normalized to preoperative T3 and rT3 levels and compared with TISS scores demonstrated a lag in alterations of serum rT3 and T3 levels relative to illness severity during recovery from cardiac surgery. We conclude (1) the euthyroid sick syndrome occurs in all pediatric cardiac surgery patients, regardless of procedure complexity, (2) changes in rT3 levels parallel but follow changes in degree of therapeutic intervention, indicating that these alterations result from, and do not cause, increasing severity of illness, (3) rT3 levels return toward normal before T3 levels, which remain low beyond the critical postoperative period, and (4) clinical indicators of illness severity are fairly well inversely correlated with T3 levels, supporting an adaptive reduction in 5'-deiodinase activity during the postoperative period. PMID- 2909709 TI - Effect of thyroid hormone level on temperament in infants with congenital hypothyroidism detected by screening of neonates. AB - To determine the effect of congenital hypothyroidism and its treatment on infant behavior, we assessed temperament in 50 six-month-old infants with congenital hypothyroidism detected by means of screening of neonates. Intelligence and temperament were also evaluated at 12, 18, 24, and 36 months. More of these children were classified as "difficult" than children in the nonhypothyroid standardization sample. Temperamental difficulty was associated with increased nervous system sensitivity, reflecting more intense responses and a lower threshold of response to external stimulation. Greater temperamental difficulty was found to persist until at least age 2 years of age and to be associated with higher circulating triiodothyronine and thyroxine levels between 1 and 3 months of age. Our results suggest that behavioral features should be considered, as well as circulating hormone levels, in determining the proper dose of thyroid hormone replacement in infants with congenital hypothyroidism. PMID- 2909710 TI - Impaired antibody response to polysaccharides in association with functional asplenia. PMID- 2909711 TI - Bacterial contamination rates in voided urine collections in girls. PMID- 2909712 TI - Bacterial contamination rates for non-clean-catch and clean-catch midstream urine collections in uncircumcised boys. PMID- 2909713 TI - Perinatal/neonatal outreach. PMID- 2909714 TI - Assessment strategies for the outreach educator. PMID- 2909715 TI - The tertiary center and health departments in cooperation: the Duke University experience. PMID- 2909716 TI - Applying principles to practice in maternal-fetal transport. PMID- 2909717 TI - Perinatal outreach: liability issues. PMID- 2909718 TI - Back-transfer in neonatal care. PMID- 2909719 TI - Perinatal outreach education: linking hospital and community in the care of high risk infants. PMID- 2909720 TI - The clients of outreach. PMID- 2909722 TI - Medicinal chemistry: 1989 and beyond. PMID- 2909721 TI - Dynamic concepts for neonatal education: developing a combined medical and nursing education program. PMID- 2909723 TI - Design, synthesis, antineoplastic activity, and chemical properties of bis(carbamate) derivatives of 4,5-bis(hydroxymethyl)imidazole. AB - A series of bis(carbamate) derivatives of 1,2-substituted 4,5 bis(hydroxymethyl)imidazoles were prepared and evaluated against murine P388 lymphocytic leukemia. Electron-withdrawing substituents at either N-1 or C-2 gave rise to inactive compounds. However, electron-donating substituents gave active compounds and the 2-(methylthio)-1-methyl derivative 2i (carmethizole), as the bis(N-methylcarbamate), was found to be very active. The derivative 2i, referred to by the name carmethizole, was also shown to be active against the MX-1 mammary xenograft, the human amelanotic melanoma cell line (LOX) xenograft, the M5076 sarcoma, and L1210 lymphocytic leukemia. The solution stability, water solubility, pKa, and log P of carmethizole are also reported. PMID- 2909724 TI - Chemical and biological properties of a new series of cis-diammineplatinum(II) antitumor agents containing three nitrogen donors: cis-[Pt(NH3)2(N-donor)Cl]+. AB - A series of 32 cationic platinum(II) complexes of the form cis-[PtA2(Am)Cl]+, where A is a monodentate (NH3 or i-PrNH2) or A2 is a bidentate (ethylenediamine or 1,2-diaminocyclohexane) amine and Am is either a heterocyclic amine based on a pyridine, pyrimidine, purine, piperidine, or a saturated amine (RNH2) ligand, was prepared and screened against in vivo murine tumor models. Each compound was tested against Sarcoma 180 ascites (S180a) in mice, with 20 members of the series showing activity (ILS greater than 50%). Antitumor activity also was demonstrated in 4 of 16 compounds tested in the L1210 murine leukemia model (ILS greater than 25%) and in 3 of 3 tested in the P388 murine leukemia model (ILS greater than 30%). The most active and potent analogues of the series were obtained when A was NH3 and Am was N1-pyridine, N1-4-methylpyridine, N1-4-bromopyridine, N1-4 chloropyridine, N3-cytosine, or N7-2'-deoxyguanosine. Complexes containing chelating and saturated amine ligands (A), as well as two trans isomers of active cis analogues (trans-[Pt(NH3)2(Am)Cl]+, where Am = N1-pyridine or N1-4 methylpyridine), were inactive in the S180a screen. All complexes were characterized by means of elemental analysis, HPLC, and 195Pt NMR spectroscopy, and the structure of one analogue, cis-[Pt(NH3)2(N3-cytosine)Cl](NO3), was determined by using single-crystal X-ray diffraction methods. While members of this series of compounds demonstrate antitumor activity in vivo, these new agents are not classical analogues of cisplatin (i.e. cis-[PtA2X2] complexes), as they contain three nitrogen donors and only one leaving group. The results of these studies suggest that further work should be conducted to better define the limits of the structure-activity relationships among platinum(II) complexes. PMID- 2909725 TI - Benzodiazepine gastrin and brain cholecystokinin receptor ligands: L-365,260. PMID- 2909726 TI - Development of phosphonate derivatives of gadolinium chelates for NMR imaging of calcified soft tissues. AB - We have synthesized several classes of gadolinium (Gd) complexes for use as NMR contrast agents in the detection of soft-tissue calcification. Class I was made up of strongly chelated GdDTPA complexes with one carboxylate arm coupled to a phosphonate-containing molecule through an amide link. Class II complexes were formed by Gd with several aminophosphonates and phosphono carboxylic acids. Class III were Gd complexes of weak chelates containing no phosphonate. The calcium seeking ability of each complex was assessed by in vivo bone uptake. Tissue distribution in normal rats showed that only the complexes of GdDTPA modified with a diphosphonate group and GdEDTMP (EDTMP is ethylenediaminetetrakis(methylenephosponate] showed adequate bone localization at the concentrations required for NMR contrast enhancement (approximately 20% of a 100 mumol/kg dose). PMID- 2909727 TI - Rationale for the synthesis and preliminary biological evaluation of highly active new antitumor nitrosoureido sugars. AB - Various new nitrosoureido derivatives of di- or trideoxy sugars were synthesized. The influence of the hydroxyl substitution pattern, the configuration at the anomeric center, and the absolute configuration of the sugar moiety on the antitumor activity of a series of nitrosoureido derivatives of di- and trideoxy sugars was studied. All compounds showed a very significant activity in vivo against L1210 leukemia, B16 melanocarcinoma, and Lewis lung carcinoma. Methyl 3 [3-(2-chloroethyl)-3-nitrosoureido]-2,3-dideoxy-alpha-D-arabino- hexopyranoside, 24 (NSC 609224), was found to be the most active compound. When treated with 24 (NSC 609224) at 20 mg/kg on day 1, at least 90% of the L1210 leukemia and B16 melanocarcinoma bearing mice showed a survival of over 60 days for a LD50 value for this compound of 42 mg/kg. PMID- 2909728 TI - Quinazoline antifolates inhibiting thymidylate synthase: synthesis of four oligo(L-gamma-glutamyl) conjugates of N10-propargyl-5,8-dideazafolic acid and their enzyme inhibition. AB - The synthesis is described of four oligo(gamma-glutamyl) conjugates of N10 propargyl-5,8-dideazafolic acid containing a total of two, three, four, and five L-glutamic acid residues. The tert-butyl group was chosen as the carboxyl protecting group in order to obviate the use of alkali and thus the possibility of gamma----alpha transpeptidation. The starting material, di-tert-butyl glutamate, was coupled to N-(benzyloxycarbonyl)-L-glutamic acid alpha-tert-butyl ester via a mixed anhydride with isobutyl chloroformate. Hydrogenolysis of the benzyloxycarbonyl group in the product gave a carboxyl-protected diglutamate, which either was acylated with 4-[(benzyloxycarbonyl)amino] benzoyl chloride to give a protected aminobenzamide or was cycled further by using the above mixed anhydride/hydrogenolysis sequence into tri-, tetra-, and pentaglutamates. Each of the last named was also acylated, as above, to give a benzamide. The benzyloxycarbonyl group in the benzamides was removed by hydrogenolysis and the amino groups thus exposed were N-alkylated with propargyl bromide. The resulting proparglyamines were further alkylated with 2-amino-6-(bromomethyl)-4 hydroxyquinazoline hydrobromide to give the antifolate poly(t-Bu) esters. Deprotection with trifluoroacetic acid in the final step delivered the desired antifolates as their trifluoroacetate salts. The di- to pentaglutamates were, respectively, 31-, 97-, 171-, and 167-fold more inhibitory to WI-L2 human thymidylate synthase than the parent compound. PMID- 2909729 TI - 2,2-Difluoro-5-hexyne-1,4-diamine: a potent enzyme-activated inhibitor of ornithine decarboxylase. AB - 2,2-Difluoro-5-hexyne-1,4-diamine was prepared in an eight-step sequence from ethyl 2,2-difluoro-4-pentenoate and tested as an inhibitor of mammalian ornithine decarboxylase. It produces a time-dependent inhibition of the enzyme in vitro which shows saturation kinetics, with KI = 10 microM and tau 1/2 = 2.4 min. In rats, it produces a rapid, long-lasting, and dose-dependent decrease of ornithine decarboxylase activity in the ventral prostate, testis, and thymus. In contrast with the nonfluorinated analogue 5-hexyne-1,4-diamine (Danzin et al. Biochem. Pharmacol. 1983, 32, 941), 2,2-difluoro-5-hexyne-1,4-diamine is not a substrate of mitochondrial monoamine oxidase. PMID- 2909730 TI - Flavones. 2. Synthesis and structure-activity relationship of flavodilol and its analogues, a novel class of antihypertensive agents with catecholamine depleting properties. AB - (3-Phenyl-7-flavonoxy)propanolamines have been shown to exhibit antihypertensive activity in spontaneously hypertensive rats. Although they are structurally similar to classical beta-adrenergic blocking compounds, their activity is not due to inhibition of beta-adrenoceptors. In the present study, a series of simple flavonoxypropanolamines was prepared to further explore the structural requirements for the antihypertensive effect of these compounds. A structure activity relationship of these derivatives indicates that the position of the oxypropanolamine side chain, the hydroxy group of the side chain, steric bulkiness and length of N substituents, degree of the N-substitution, phenyl group at the 2-position of the chromone nucleus, and substituents of the phenyl group or B ring of the flavone play significant roles in imparting pharmacological effects. In addition, there is a good correlation between the antihypertensive activity and depletion of myocardial norepinephrine. Of these analogues tested, the most effective one was flavodilol. Only the 8-substituted analogue 6 was found to be a beta-antagonist. Flavodilol was chosen for in-depth pharmacological, toxicological, and clinical evaluation. PMID- 2909732 TI - Synthesis and biological evaluation of a monocyclic, fully functional analogue of compactin. AB - Compound 8, a monocyclic analogue of compactin, has been prepared and its efficacy as an inhibitor of 3-hydroxy-3-methylglutarylcoenzyme A reductase (HMGR) evaluated. The synthesis (Schemes I and II) requires seven steps starting with di (-)-menthyl fumarate and employs the useful RR-phosphonate reagent 14 to attach the mevinic acid side chain to aldehyde 13. A molecular mechanics study shows that the preferred conformations of 18 (a model for compactin) and 19 (a model for 8) are nearly identical. Compound 8 inhibits HMGR with IC50 = 320 microM, compared to a corresponding value of 32 nM for the compactin ketone, 5. The factor of 10,000 difference in the two inhibitors corresponds to a difference in binding energy of 5.45 kcal mol-1, or 1.36 kcal mol-1 for each of the four carbons of 5 that are missing in analogue 8. This quantitative difference is consistent with the idea that the decalin moiety of the mevinic acids play a purely hydrophobic role in binding the inhibitors to the enzyme. PMID- 2909731 TI - Phenolic metabolites of clomiphene: [(E,Z)-2-[4-(1,2-diphenyl-2 chlorovinyl)phenoxy]ethyl]diethylamine. Preparation, electrophilicity, and effects in MCF 7 breast cancer cells. AB - The triarylethylene antiestrogen clomiphene was previously shown to undergo biotransformation to an active metabolite, 4-hydroxyclomiphene, and to 3-methoxy 4-hydroxyclomiphene plus the respective regioisomers of these, 4 and 5. We now report the synthesis and further chemical and biochemical studies on 3-5. Coupling of 4-[2-(diethylamino)ethoxy]benzophenone with either 4 (benzyloxy)benzaldehyde or its 3-methoxy analogue 11b in the presence of titanium, followed by chlorination and deprotection of the intermediate triarylethylenes, gave 4 and 5, respectively. Condensation of benzylmagnesium chloride with the (2-methoxyethoxy)methyl (MEM) ether of 4-[2 (diethylamino)ethoxy]-3'-methoxy-4'-hydroxybenzophenone, followed by mild acid treatment, afforded deschloro 3 due to facile MEM ether hydrolysis. Acetylation of this, followed by chlorination and deacetylation, gave 3. Compounds 4 and 5 reacted readily with nucleophiles. In particular, 2-mercaptoethanol reacted with 4 to afford deschloro vinyl thioether 13 as suggested by NMR spectral studies, a result that implicated allene-quinone 14 as the electrophilic species produced in solution from 4. Antiestrogen binding sites and estrogen receptors from MCF 7 human breast cancer cells interacted with 3 and 5 with affinities comparable to those of tamoxifen and 1, respectively; 5 was shown not to bind irreversibly with these sites. Inhibition of MCF 7 cell proliferation by 3-5 at 5 microM concentrations (76%, 57%, and 49%, respectively, relative to drug-free controls) compared favorably to that observed with 5 microM 1 (80%). These results suggest that 3-5 as well as 2 may contribute to the antiestrogenic effects of 1. PMID- 2909733 TI - Interactions of thiol-containing androgens with human placental aromatase. AB - A series of thiol androgens were synthesized and investigated to characterize structural features important for the inhibition of aromatase. Analogues of androstenedione with thiol groups in either the 2 alpha-, 10 beta-, or 19 positions caused time-dependent inhibition of human placental aromatase. When their KI and kcat values were compared with those of 4-hydroxyandrost-4-ene-3,17 dione (4-OHa) and 10 beta-propargylestr-4-ene-3,17-dione (PED), the thiol androgen 10 beta-mercaptoestr-4-ene-3,17-dione (10 beta-SHnorA) proved to be the most potent suicide substrate. However, 19-mercaptoandrost-4-ene-3,17-dione (19 SHA) was the best all-around inhibitor. All compounds except 19-SHA exhibited normal type I P-450 difference spectra with partially purified/solubilized, human placental aromatase. The Ks values for the series of compounds compared qualitatively to the KI values determined from the time and concentration dependent inhibition experiments. 19-SHA induced split Soret peaks at 380 and 474 nm, which suggested binding of the 19-thiolate directly to the ferric iron of aromatase. This binding could be displaced by aminoglutethimide but not by androstenedione. The inhibitory activity of 19-SHA may be explained by two independent mechanisms: (1) suicide inactivation of aromatase in the ferrous state; and (2) a direct "hyper-type II" binding to the remaining portion of the cytochrome in the ferric state. A free thiol group was necessary for the suicide inhibitory activity of 19-SHA; time-dependent inactivation of aromatase by 19 (acetylthio)androst-4-ene-3,17-dione (19-SAcA) and 19-xanthogenylandrost-4-ene 3,17-dione (19-XanA) could be prevented if the microsomes were preincubated with a carboxyesterase inhibitor. Aromatase previously inactivated by either thiol androgens,4-OHA, or PED could not be reactivated after incubation with the disulfide reducing agent dithiothreitol, which suggests that a disulfide bond may not be involved in aromatase inactivation by these inhibitors. PMID- 2909734 TI - Synthesis and P-388 antitumor properties of the four diastereomeric 1-hydroxy-3,4 diaminocyclohexane-Cl2PtII complexes. AB - Synthesis and antileukemic activity in vivo of the four diastereomeric 1-hydroxy 3,4-diaminocyclohexane-Cl2PtII complexes (Cl2PtII-3a-d) are described. Respective bis(phenylmethyl) (1 alpha,2 alpha,4 beta)-, (1 alpha,2 alpha,4 alpha)-, (1 alpha,2 beta,4 beta)-, and (1 alpha,2 beta,4 alpha)-(4-hydroxy-1,2 cyclohexanediyl)bis(carbamates) (5a, 5b, 7a, 7b) were prepared by hydroboration oxidation of the bis(carbobenzoxyamino) derivatives (4,5) of cis- and trans-4,5 diaminocyclohexene. The relative stereochemistry of intermediates 5a and 5b was established by correlation with the alcohol obtained by NaBH4 reduction of bis(phenylmethyl) (1 alpha,2 alpha,3 alpha,4 alpha)-(3,4-epoxy-1,2 cyclohexanediyl)bis(carbamate) (8), the all-cis stereochemistry of which was unambiguously determined by X-ray crystallographic analysis. In the P-388 murine leukemia model these monohydroxycyclohexanediamine-PtII complexes were more effective than the PtII complexes of the related diol diamines 1a-e but were less active than the cisplatin positive control. PMID- 2909735 TI - Synthesis of acylguanidine analogues: inhibitors of ADP-induced platelet aggregation. AB - Routine screening of compounds for inhibition of ADP-induced platelet aggregation in vitro revealed that 1,1'-hexamethylenebis[3-cyclohexyl-3-[(cyclohexylimino) (4 morpholinyl) methyl]urea] (1) was active and represented the first example of a bis(acylguanidine) with possible antithrombotic activity. In order to develop a structure-activity relationship for this class of compounds, we synthesized a number of new bis(acylguanidines). These were tested in vitro, and several analogues were also active. Ex vivo testing revealed that compounds 22, 41, 58, and 70-73 were orally active in rats or guinea pigs. PMID- 2909736 TI - Hypoxia-selective antitumor agents. 1. Relationships between structure, redox properties and hypoxia-selective cytotoxicity for 4-substituted derivatives of nitracrine. AB - The nitroacridine derivative 9-[[3-(dimethylamino)propyl]amino]-1-nitroacridine (nitracrine) is selectively cytotoxic to hypoxic tumor cells in culture. However, the compound undergoes reductive metabolism too rapidly, with the reduction not being sufficiently inhibited by molecular oxygen in aerobic tissues, for it to demonstrate the same activity in vivo. In a search for derivatives with lower reduction potentials, we have synthesized and evaluated a series of derivatives bearing 4-substituents with a wide range of electronic properties. The one electron reduction potentials (E(1] of these compounds, when compared under conditions of equivalent ionization, were highly correlated with sigma p values. However, at pH 7 the influence of substituent electronic properties was modified by prototrophic equilibria, with the basic nature of the acridine limiting the extent to which ring substituent electronic effects can be used to modulate reduction potential of the 1-nitro group. Nevertheless, comparison of the kinetics of the killing of AA8 cells under hypoxia suggests that some metabolic stabilization of the compounds can be achieved by the use of electron-donating substituents, with such compounds retaining the hypoxia-selective toxicity of nitracrine in cell culture. However, the 4-substituted nitracrines show no clear relationship between E(1) and cytotoxic potency, in distinct contrast to simpler nitroheterocycles such as nitroimidazoles. PMID- 2909737 TI - 2-O-alkyltyrosine derivatives of 1-deamino-arginine-vasopressin: highly specific and potent antidiuretic agonists. AB - We report the solid-phase synthesis of eight 2-O-alkyltyrosine analogues of 1 deamino-arginine-vasopressin (dAVP) with enhanced antidiuretic agonistic specificity. These peptides are as follows: 1-deamino[2-O-methyltyrosine] arginine-vasopressin (dTyr(Me)AVP), 1-deamino[2-O-ethyltyrosine]arginine vasopressin (dTyr(Et)AVP), 1-deamino[2-O-methyltyrosine,8-D-arginine]vasopressin (dTyr(Me)DAVP), 1-deamino[2-O-ethyltyrosine,8-D-arginine]vasopressin (dTyr(Et)DAVP), 1-deamino[2-O-methyltyrosine,4-valine]arginine-vasopressin (dTyr(Me)VAVP), 1-deamino[2-O-ethyltyrosine,4-valine]arginine-vasopressin (dTyr(Et)VAVP), 1-deamino[2-O-methyltyrosine,4-valine,8-D-arginine]vasopressin (dTyr(Me)VDAVP), and 1-deamino[2-O-ethyltyrosine,4-valine,8-D arginine]vasopressin (dTyr(Et)VDAVP). All analogues were tested for antidiuretic, antivasopressor, and antioxytocic activities. Deamination, as was expected, significantly enhanced the antidiuretic properties of these analogues relative to their parent N-amino-O-alkyltyrosine peptides. With the exception of dTyr(Me)AVP, all of these analogues are antagonists of the vasopressor responses to AVP and of the uterine response to oxytocin. Thus they all exhibit high antidiuretic agonistic specificity. Due to its remarkable properties, dTyr(Me)VDAVP is a unique compound in this series. It appears to be the most potent antidiuretic agonist (1740 units/mg) and also a vasopressor antagonist and a potent oxytocin antagonist. It is thus a highly specific antidiuretic agonist. In general, all of these new analogues are highly specific and thus are potentially useful as pharmacological tools and clinical agents. PMID- 2909738 TI - Mitomycin C analogues with a substituted hydrazine at position 7. Synthesis, spectral properties, and biological activity. AB - A select number of mitomycin C derivatives with a substituted hydrazine group at position 7 were synthesized and tested for antineoplastic activity by using an in vivo test with murine P388 leukemia. Several of the adducts displayed activity comparable to that of mitomycin C. The X-ray-determined crystal structure of one of the derivatives (3f) is reported. PMID- 2909739 TI - Prostaglandin photoaffinity probes: synthesis and biological activity of azide substituted 16-phenoxy- and 17-phenyl-PGF2 alpha prostaglandins. AB - The development of a prostaglandin PGF2 alpha photoaffinity probe led to the synthesis and biological evaluation of azide-substituted 17-phenyl-18,19,20 trinorprostaglandin F2 alpha and 16-phenoxy-17,18,19,20-tetranorprostaglandin F2 alpha derivatives. Two approaches for the preparation of iodinated versions of these prostaglandins were evaluated: (1) iodination of a phenyl azide bearing an activating hydroxyl group and (2) iodination of an aniline precursor to the phenyl azide group and subsequent conversion of the aniline to the phenyl azide. In the first approach, 17-(4-azido-2-hydroxyphenyl)-18,19,20-trinorprostaglandin F2 alpha, 16-(5-azido-3-hydroxyphenoxy)-17,18,19,20-tetranorprostaglandin F2 alpha, and 16-(4-azido-2-hydroxyphenoxy)-17,18,19,20-tetranorprostaglandin F2 alpha were prepared by using the Corey synthesis, but were biologically inactive presumably as a result of the hydrophilic phenolic hydroxyl group. In the second approach, the iodination of a 17-(4-aminophenyl)-18,19,20-trinorprostaglandin F2 alpha derivative delivered 17-(4-azido-3-iodophenyl)-18,19,20-trinorprostaglandin F2 alpha, which exhibited competitive binding with natural [3H]PGF2 alpha to ovine luteal cells and to plasma membranes of bovine corpora lutea. [125I]-17-(4 Azido-3-iodophenyl)-18,19,20-trinorprostaglandin F2 alpha was utilized in a preliminary photoaffinity cross-linking experiment. PMID- 2909740 TI - Hypolipidemic 2-[4-(1,1-dimethylethyl)phenyl]-4H-3,1-benzoxazin-4-ones. Structure activity relationships of a novel series of high-density lipoprotein elevators. AB - The preparation and plasma lipid altering characteristics of a series of 4H-3,1 benzoxazin-4-ones are described. Hypocholesterolemic, hypotriglyceridemic, and high-density-lipoprotein elevating properties are found for derivatives bearing a 4-(1,1-dimethylethyl)phenyl group at the 2-position, and this activity is displayed in both hypercholesterolemic and in normolipidemic rats when the ring system is substituted at position 6 with hydrogen, methyl, chloro, or iodo groups, and is optimal when the 6-position is substituted by a bromine atom. Evidence is presented suggesting that a metabolite or degradation product is responsible for the changes in lipoprotein concentration observed with active molecules of this type. Synthesis of anticipated degradation products of the active molecules gave products displaying the expected in vivo activity, but no improvement in the narrow therapeutic margin of the best compound, 6-bromo-2-[4 (1,1-dimethylethyl)phenyl]-4H-3,1-benzoxazin-4-one, was obtained. PMID- 2909741 TI - Hypoxia-selective antitumor agents. 2. Electronic effects of 4-substituents on the mechanisms of cytotoxicity and metabolic stability of nitracrine derivatives. AB - The mechanism of cytotoxicity of a series of 4-substituted derivatives of 9-[[3 (dimethylamino)propyl]amino]-1-nitroacridine (nitracrine) has been studied, using a panel of DNA repair-defective mutants of the Chinese hamster ovary cell line AA8. Cell lines UV-4 and UV-5 were hypersensitive to nitracrine, with sensitivities approximately 10-fold greater than that of AA8, while EM-9 showed a hypersensitivity factor (HF) of about 2-fold. This pattern suggests the major cytotoxic lesions induced by nitracrine are bulky DNA monoadducts, rather than DNA interstrand cross-links as previously suggested. The desnitro analogue of nitracrine, which retains the intercalative potential of the latter but cannot be metabolically activated by nitro reduction, showed no hypersensitivity, indicating the specificity with which this panel of cell lines can discriminate different types of DNA damage. Several of the highly cytotoxic 4-substituted nitracrine derivatives showed HFs similar to that of the parent, but the less potent 4-dialkylamino and 4-COOMe derivatives showed much lower HFs for UV-4, suggesting that different mechanisms of cytotoxicity contribute. All compounds showed similar HFs under both aerobic and hypoxic conditions, indicating that hypoxia-selective toxicity in this series is due to a quantitative rather than qualitative change in the presence of oxygen. Rates of metabolic consumption of the compounds were measured under both aerobic and hypoxic conditions by bioassay against the sensitive UV-4 cell line. The results agreed well with previous inferences on metabolic stability derived from cell-killing kinetics and showed that electron-donating 4-substituents can be used to increase metabolic stability in vitro. Such stabilization may enhance the therapeutic utility of the nitroacridines in cancer therapy since rapid metabolism of nitracrine appears to prevent its activity against hypoxic cells in solid tumors. PMID- 2909742 TI - 5-Isoquinolinesulfonamide derivatives. 1. Synthesis and vasodilatory activity of N-(2-guanidinoethyl)-5-isoquinolinesulfonamide derivatives. AB - Two novel series of N-(2-guanidinoalkyl)-5-isoquinolinesulfonamides, 2 and 3, were prepared. Many of the compounds possessed vasodilatory activity when injected locally into the femoral artery of dogs. The most potent compound, 1 amidino-4-(5-isoquinolylsulfonyl)-1,4-perhydrodiazepine, 33, was comparable to diltiazem, which is used clinically as a vasodilator. PMID- 2909743 TI - 5-Isoquinolinesulfonamide derivatives. 2. Synthesis and vasodilatory activity of N-(2-aminoethyl)-5-isoquinolinesulfonamide derivatives. AB - A new series of aromatic sulfonamides, the N-(2-aminoethyl)-5 isoquinolinesulfonamide derivatives, 3, was synthesized from 5 isoquinolinesulfonic acid and shown to possess vasodilatory action. Vasodilatory activity was evaluated in vivo in terms of increases in arterial blood flow in dogs after local injection in the femoral and/or vertebral arteries. When the alkylene group between the two nonaromatic nitrogen atoms was ethylene, the most potent activity was obtained. Alkylations of either of the two nonaromatic nitrogens yielded more active compounds, although bulky or excessively long alkyl groups reduced the potency. Among these derivatives, 27 and 47 were equipotent to diltiazem, which is used clinically as a cardiovascular drug. These two compounds also had antihypertensive and vasodilatory activities when administered intravenously, although the activities were less than that of diltiazem when given by this route. PMID- 2909744 TI - Platelet activating factor antagonists: synthesis and structure-activity studies of novel PAF analogues modified in the phosphorylcholine moiety. AB - New analogues of platelet activating factor (PAF), in which the phosphate and trimethylammonium moieties were replaced with an acylcarbamoyl moiety and a quaternary cyclic ammonium group, were synthesized. Their biological activities as PAF antagonists were evaluated by the inhibition of PAF-induced rabbit platelet aggregation in vitro and protective effects on PAF-induced hypotension in rats and PAF-induced death in mice. Investigation of structure-activity relationships revealed that PAF antagonist activity is strongly influenced by the acyl substituent of the nitrogen atom on the carbamoyl group and the nature of the polar head group at the 3-position of the glycerin backbone. Among the compounds tested, 2-[[N-acetyl-N-[[2-methoxy-3-[ (octadecylcarbamoyl)oxy]propoxy] carbonyl]amino] methyl]-1-ethylpyridinium chloride (21, CV-6209) was one of the most potent compounds in the in vitro assay (IC50 = 7.5 X 10(-8) M) and the most potent and long-lasting in the in vivo assays. (R)-(-)-21 and (S)-(+)-21 were also synthesized, and no significant differences were observed in PAF antagonist activity in vitro and an inhibitory effect on PAF induced hypotension in vivo between (RS)-21 and its enantiomers. PMID- 2909745 TI - Acyclic analogues of 3'-azido-3'-deoxythymidine as potential antiviral agents. Nucleoside synthesis by Michael addition. AB - An acyclic derivative of 3'-azido-3'-deoxythymidine, (R,S)-1-[1-(2-hydroxyethoxy) 3-azidopropyl]thymine (2), has been synthesized by a path involving Michael-type addition. Related thymidine analogues lacking the C(3')-C(4') bond were similarly obtained. The method provides a versatile new route to nucleoside analogues. The new compounds were found to be essentially inactive against human immunodeficiency virus type 1 (HIV-1) and herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in vitro when tested up to 100 microM. PMID- 2909746 TI - 1',2'-seco-dideoxynucleosides as potential anti-HIV agents. AB - 1',2'-seco-2',3'-Dideoxycytidine (12), -guanosine (14), -adenosine (16), and inosine (18) were prepared from (R)-benzylglycidol as potential anti-HIV agents. When compared to ddAdo in protecting ATH8 cells, they were found to be inactive. PMID- 2909747 TI - Structure-activity relationships among methoctramine-related polymethylene tetraamines. Chain-length and substituent effects on M-2 muscarinic receptor blocking activity. AB - Several polymethylene tetraamines related to methoctramine (1) were prepared and evaluated for their blocking activity on M-2 muscarinic receptors in guinea pig atria and ileum. It turned out that antimuscarinic potency depends on the following parameters: (a) nature of the substituent on both inner and outer nitrogens and (b) carbon chain length separating the inner nitrogens as well as the inner and outer nitrogens. Optimum activity at cardiac M-2 muscarinic receptors was associated with the chain lengths present in 1, that is, eight methylenes between the inner nitrogens and six methylenes between the inner and outer nitrogens. With regard to the substituents, replacement of the benzylic moiety of 1 by a 2-furyl or a 5-methyl-2-furyl nucleus resulted in enhanced potency toward cardiac M-2 muscarinic receptors. In fact, furtramine (18) and mefurtramine (19) proved to be more potent and more selective than 1. Moreover, N methylation of the four nitrogens of 1 gave different effects: methylation of the outer nitrogens, giving 22, caused a significant decrease in activity whereas methylation of the inner nitrogens, yielding 23, resulted in an increase in activity in both atria and ileum. PMID- 2909748 TI - N6-bicycloalkyladenosines with unusually high potency and selectivity for the adenosine A1 receptor. PMID- 2909749 TI - Inhibition of 125I-labeled ristocetin binding to Micrococcus luteus cells by the peptides related to bacterial cell wall mucopeptide precursors: quantitative structure-activity relationships. AB - Quantitative structure-activity relationships (QSAR) of N-Ac amino acids, N-Ac dipeptides, and N-Ac tripeptides in inhibition of 125I-labeled ristocetin binding to Micrococcus luteus cell wall have been developed to probe the details of the binding between ristocetin and N-acetylated peptides. The correlation equations indicate that (1) the binding is stronger for peptides in which the side chain of the C-terminal amino acid has a large molar refractivity (MR) value, (2) the binding is weaker for peptides with polar than for those with nonpolar C-terminal side chains, (3) the N-terminal amino acid in N-Ac dipeptides contributes 12 times that of the C-terminal amino acid to binding affinity, and (4) the interactions between ristocetin and the N-terminal amino acid of N-acetyl tripeptides appear to be much weaker than those with the first two amino acids. PMID- 2909750 TI - Synthesis and anticonvulsant properties of 2,3,3a,4-tetrahydro-1H-pyrrolo[1,2 a]benzimidazol-1-ones. AB - A series of 2,3,3a,4-tetrahydro-1H-pyrrolo[1,2-a]benzimidazol-1-ones were synthesized and evaluated for anticonvulsant activity in DBA/2 mice against sound induced seizures and in rats against maximal electroshock-induced seizures. Most of the derivatives showed an anticonvulsant effect better than that of valproate, a commonly used anticonvulsant drug. Compound 3 possessed an anticonvulsant activity comparable to that of diphenylhydantoin in both tests and was selected for further studies. Structure-activity relationships are discussed. PMID- 2909751 TI - Community-based strategies for cancer prevention in an urban area: the Stockholm Cancer Prevention Program. PMID- 2909752 TI - Phase I trial of trimetrexate glucuronate on a five-day bolus schedule: clinical pharmacology and pharmacodynamics. AB - Trimetrexate glucuronate (TMTX), a nonclassical folate antagonist, has been evaluated clinically on several schedules. We have studied TMTX administered as an iv bolus for 5 consecutive days every 3 weeks in 35 patients with advanced solid tumors. Drug was given at doses ranging from 7.6 to 18.8 mg/m2. The maximal tolerated dose was 13.1 mg/m2 per day x 5 for patients without prior myelotoxic treatment and 7.6 mg/m2 per day x 5 for previously treated patients. Because of wide individual differences in drug tolerance, dose escalation in 25% increments is recommended for patients not experiencing toxic effects. The dose-limiting toxicity was neutropenia. Rash and mucositis were also significant. TMTX concentrations were measured 1 and 24 hours after each dose, and the data were fit by use of a one-compartment pharmacokinetic model. With this simplified sampling and modeling scheme, the mean total body clearance (+/- SD) of trimetrexate was 31 +/- 20 mL/min per m2 and the volume of distribution was 13 +/ 7 L/m2. Mean plasma concentrations 1 hour after a dose were 1.12, 2.43, 3.33, and 3.25 mumol/L at 7.6, 9.1, 10.9, and 13.1 mg/m2, respectively. The mean TMTX concentration (+/- SD) 24 hours after a dose was 114 +/- 87 nmol/L. The mean area under the concentration-versus-time curve at 13.1 mg/m2 was 2,266 mumol.min/L. The drug concentration 1 hour after the first dose and the area under the concentration-versus-time curve were highly correlated with leukopenia and thrombocytopenia (r = .6 and .65 and P = .0007 and .0001, respectively). The maximal tolerated dose on the daily x 5 schedule was 30% of the dose tolerated on an iv bolus schedule. The choice of drug schedule for clinical trials when murine and human pharmacokinetics differ is discussed. Phase II trials are under way with both the iv bolus and the daily x 5 schedules. PMID- 2909753 TI - Enhanced induction by high-cholesterol diet of remnant gastric carcinogenesis by N-methyl-N'-nitro-N-nitrosoguanidine in rats. AB - The influence of bile acids on the development of remnant gastric carcinoma was examined by investigating the incidence of carcinogenesis in noninbred male Wistar rats treated orally with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG; CAS 70-25-7; 1-methyl-3-nitro-1-nitrosoguanidine) and fed a diet containing 1% cholesterol. The high-cholesterol diet did not influence the incidence of carcinoma in the nongastrectomized, MNNG-treated groups of rats. However, in the gastrectomized groups, the incidence of carcinoma was significantly higher in the group given the high-cholesterol diet (60.6%) than in the group given a normal diet (35.5%). Histologically undifferentiated adenocarcinoma was recognized more frequently in the high-cholesterol-diet group. Three gastrectomized rats not treated with MNNG but fed the high-cholesterol diet developed remnant gastric carcinoma (13%), whereas none of the rats given the normal diet did. Because the fecal excretion of bile acids increased significantly in the rats fed the high cholesterol diet and the gastroduodenal reflux of bile acids was probably accelerated, the increase in the incidence of carcinogenesis in the remnant stomach was considered to be the result of the increase in the reflux of bile acids evoked by a high-cholesterol diet. PMID- 2909755 TI - Distribution and activity of antineoplastic drugs in a tumor model. AB - Antineoplastic drugs can be effective in solid tumors only if they can penetrate several cell layers and retain their activity in the tumor microenvironment. The capacity of several common chemotherapeutic agents to meet these requirements was evaluated in an in vitro tumor model, V79 Chinese hamster cells grown as spheroids. The delivery and toxicity of radioactively labeled 5-fluorouracil, lomustine, tetraplatin, and chlorambucil were determined by use of cell-sorting techniques to select cells as a function of their position (depth) within these spheroids, and the delivery and toxicity of doxorubicin (DOX) were evaluated on the basis of fluorescence intensity. Simultaneous measurement of drug level and toxicity in cells at the time of recovery from different depths within the spheroids led to the conclusion that drug delivery was a problem only for DOX. In contrast, several of the other agents showed a dissociation between cellular drug levels and activity, implicating a major role of the cellular microenvironment in modulating drug toxicity. PMID- 2909754 TI - Control of a murine plasmacytoma with doxorubicin-cisplatin: dependence on circadian stage of treatment. AB - In anticipation of the development of clinical chronotherapy and in order to pick clinical test times for doxorubicin and cisplatin trials, two large studies were performed on rats bearing a transplanted plasmacytoma. The circadian timing of each of two anticancer drugs given at precisely equal dose intensities was expected to improve therapeutic benefit over conventionally given (time unqualified) treatment. In each chronotherapeutic study, maximal benefit and minimal toxic effects were found when cisplatin was administered in the middle to latter part of the daily activity (dark) span, while doxorubicin was administered near the end of the daily resting (light) span for these nocturnally active rodents living on a 12-hour-12-hour or 8-hour-16-hour light-dark schedule. This was true whether doxorubicin or cisplatin was given first and whether there was a lag of only a few hours or a few days between the administration of these two agents. PMID- 2909756 TI - Development of a rapid chemosensitivity test for anticancer drugs with contact sensitive monolayers of Balb/3T3 cells. AB - We investigated whether lethally irradiated, contact-sensitive Balb/3T3 cell confluent monolayers, termed "cell mats," could be used for the screening of human tumors for sensitivity to anticancer drugs. Cell mats greatly inhibited the growth of normal Balb/3T3 cells and normal human fibroblasts but did not inhibit the growth of human tumor cells. To assess chemosensitivity of tumor cells, we measured the [14C]thymidine (dThd) incorporation by tumor cells that had been plated and then treated with various anticancer drugs on the cell mats. Although the [14C]dThd incorporation assay, when compared with the colony-formation assay, underestimated the toxicity of certain drugs, the assays gave similar results with regard to the degree of colony inhibition and to the decrease in [14C]dThd incorporation when various anticancer drugs were used at the same concentration ranges. Therefore, the method we used for measuring the isotope uptake in the cell mats could also be used to test for tumor-specific chemosensitivity. Because our results from this assay on various human tumor cells, including those from primary human tumors, can be obtained within 5 days, we believe that the system is potentially useful for testing anticancer drugs against human tumors in vitro. PMID- 2909757 TI - Reversal of 5-fluorouracil-induced myelosuppression by prolonged administration of high-dose uridine. AB - The effect of high-dose uridine on 5-fluorouracil (5-FU)-induced toxicity was investigated. Nine patients were treated weekly with 5-FU at increasing dosages. Five patients developed dose-limiting leukopenia, and four patients developed thrombocytopenia. At dose-limiting toxicity, 5-FU treatment was repeated and followed after 3 hours by intermittent iv infusion of uridine (2 g/m2 per hr) during 72 hours. Leukopenia was reversed for several weeks but thrombocytopenia was not. Side effects consisted of mild rises in body temperature. The pharmacokinetics of uridine were similar to those observed with single-agent uridine. Our data indicate that high-dose uridine can reduce the severity of 5-FU induced myelosuppression. PMID- 2909758 TI - Allium vegetables and reduced risk of stomach cancer. AB - Interviews with 564 patients with stomach cancer and 1,131 controls in an area of China where gastric cancer rates are high revealed a significant reduction in gastric cancer risk with increasing consumption of allium vegetables. Persons in the highest quartile of intake experienced only 40% of the risk of those in the lowest. Protective effects were seen for garlic, onions, and other allium foods. Although additional research is needed before etiologic inferences can be made, the findings are consistent with recent reports of tumor inhibition following administration of allium compounds in experimental animals. PMID- 2909759 TI - Perspective: what makes a cell run wild? PMID- 2909760 TI - Huge tobacco control project begun by NCI, ACS. PMID- 2909761 TI - New technique to diagnose eye cancer being tested. PMID- 2909762 TI - Ban to be lifted on research use of fetal tissue? PMID- 2909763 TI - Educating farmers, physicians who treat them, about rural life's potential health hazards. PMID- 2909764 TI - Increasing use of contact lenses prompts issuing of infection-prevention guidelines. PMID- 2909765 TI - Institute of Medicine panel suggests changes to revitalize National Institutes of Health. PMID- 2909766 TI - From the Food and Drug Administration. Interferon alfa approved for Kaposi's sarcoma. PMID- 2909767 TI - Leads from the MMWR. Relationship of syphilis to drug use and prostitution- Connecticut and Philadelphia, Pennsylvania. PMID- 2909768 TI - Leads from the MMWR. Premature mortality due to alcohol-related motor vehicle traffic fatalities--United States, 1987. PMID- 2909769 TI - Leads from the MMWR. Operational criteria for determining suicide. PMID- 2909770 TI - New York City's health care crisis: AIDS, the poor, and limited resources. PMID- 2909771 TI - Caring for the poor: the altruism of physicians. PMID- 2909772 TI - Doctors have feelings too. PMID- 2909773 TI - Organ procurement. PMID- 2909774 TI - Ulcerative colitis and diffuse interstitial lung disease: rare association or complete coincidence? PMID- 2909775 TI - The office measurement of cholesterol. PMID- 2909776 TI - Collection agencies: instant destruction of goodwill. PMID- 2909777 TI - Meta-analysis of alcohol and risk of breast cancer. PMID- 2909778 TI - Increasing incidence of tuberculosis in a prison inmate population. Association with HIV infection. AB - The incidence of tuberculosis (TB) among inmates of the New York State prison system increased from 15.4 per 100,000 in 1976 through 1978 to 105.5 per 100,000 in 1986. Matching of TB and acquired immunodeficiency syndrome registries indicated that the majority (56%) of inmates with TB reported in 1985 and 1986 had acquired immunodeficiency syndrome or human immunodeficiency virus infection; none were known to be human immunodeficiency virus seronegative. A case-control study examined 59 inmates with TB reported from 1984 through 1986 and 59 matched control inmates without TB. Inmates who reported street drug use were more likely to develop TB: odds ratio, 9.7; 95% confidence interval, 2.8 to 33.6 and odds ratio, 7.3; 95% confidence interval, 0.9 to 59.3 by unconditional and conditional logistic regression analyses, respectively. Although the majority of cases are thought to be due to reactivation of latent infection, phage typing of 16 Mycobacterium tuberculosis cultures suggested the possibility of inmate-to-inmate transmission in at least one cluster of three cases. It is of crucial importance that TB control measures be reinforced in the prison setting to counter the increased risk created by human immunodeficiency virus infection. PMID- 2909779 TI - Effect of smoking on the activity of ischemic heart disease. AB - Cigarette smoking has been causally linked to coronary heart disease. To investigate the effect of smoking on the activity of ischemic heart disease, 65 patients with chronic stable manifestations of coronary disease and a positive exercise tolerance test underwent continuous ambulatory monitoring to quantify the amount of ischemic ST segment depression during daily life. Twenty-four smokers were compared with 41 nonsmokers for frequency and duration of electrocardiographic signs of ischemia during 24 hours. A total of 4,968 hours of ambulatory monitoring were analyzed. The frequency of episodes was three times as often (median) and the duration of ischemia was 12 times longer (median duration, 24 vs 2 min/24 h) in smokers than nonsmokers. This finding remained statistically significant when a number of potentially confounding factors were controlled by means of logistic regression. This study shows that patients with coronary artery disease who smoke have significantly and substantially more active myocardial ischemia during daily life than patients who do not. PMID- 2909780 TI - Prevalence, detection, and treatment of alcoholism in hospitalized patients. AB - As part of an institution-wide program to enhance the education of physicians in diagnosing and treating alcohol dependence and abuse, a comprehensive survey was conducted in which all new admissions to the adult inpatient services of The Johns Hopkins Hospital were screened for alcoholism. The prevalence of screen positive alcoholism, by department, was as follows: medicine (25%), psychiatry (30%), neurology (19%), obstetrics-gynecology (12.5%), and surgery (23%). Detection rates by the house staff and faculty physicians caring for those patients who screened positively were less than 25% in surgery and obstetrics gynecology, between 25% and 50% in neurology and medicine, and greater than 50% in psychiatry. However, physicians were less likely to identify as alcoholic those patients with higher incomes, higher education, or private medical insurance; women; and those who denied heavy alcohol intake. Physician-instituted treatment rates for those patients diagnosed by the physician as having nonrecovered alcoholism were less than 50% in surgery and obstetrics-gynecology, between 50% and 75% in medicine and neurology, and 100% in psychiatry. The extent to which the physicians intervened while the patient was hospitalized correlated with the patient's reported change in alcohol use after discharge. Recommendations based on these data are being incorporated into the medical education curriculum. PMID- 2909781 TI - Passive transfer of HIV antibody by hepatitis B immune globulin. AB - Two newborns of mothers carrying hepatitis B and at high risk for human immunodeficiency virus (HIV) infection developed HIV-positive test results by enzyme-linked immunosorbent assay and Western blot tests after birth. Both had been administered hepatitis B immune globulin within 48 hours of birth. Serological tests detected HIV antibody as long as 17 days after birth. Both newborns had received lots of hepatitis B immune globulin containing antibody to HIV. While hepatitis B immune globulin cannot transmit HIV infection to recipients, physicians should be aware that administration of older lots of this preparation may result in transiently positive tests for HIV antibody in the recipients. Lots manufactured from screened plasma do not contain antibody to HIV. PMID- 2909782 TI - Tuberculosis in correctional institutions. PMID- 2909783 TI - Another smoking gun linking cigarettes and heart disease. PMID- 2909784 TI - A piece of my mind. On taking up the caduceus. PMID- 2909785 TI - A piece of my mind. The Benjamin birds. PMID- 2909786 TI - Is it time to include lipoprotein analysis in cholesterol screening? PMID- 2909787 TI - Cardiomyoplasty adds muscle to efforts to alleviate end-stage heart failure. PMID- 2909788 TI - Approval expected for 'prelude' to gene therapy. PMID- 2909789 TI - Leads from the MMWR. Hypothermia prevention. PMID- 2909790 TI - Lipid level alterations in the Helsinki Heart Study. PMID- 2909791 TI - The care of patients with AIDS: don't ignore the family practitioner. PMID- 2909792 TI - Enough about AIDS: another letter about AIDS. PMID- 2909793 TI - An 'amp' by any other name: the hazards of intravenous magnesium dosing. PMID- 2909794 TI - Corneal damage due to eye contact with chlorhexidine gluconate. PMID- 2909795 TI - Laugh if this is a joke. PMID- 2909796 TI - In-flight medical emergencies. PMID- 2909797 TI - The efficacy of acellular pertussis vaccine. PMID- 2909798 TI - Cocaine use and HIV infection in intravenous drug users in San Francisco. AB - We assessed risk factors for human immunodeficiency virus (HIV) infection in 633 heterosexual intravenous drug users. The HIV seroprevalence was 26% in blacks, 10% in Hispanics, and 6% in whites. Intravenous cocaine use significantly increased the risk of HIV infection, with a seroprevalence of 35% in daily cocaine users (odds ratio, 6.4; 95% confidence interval, 3.0 to 13.3). Black subjects were more likely to use cocaine regularly. Drug use in shooting galleries and sharing of drug injection equipment were also associated with HIV infection and were more common in cocaine users. By multivariate analysis, black race, daily cocaine injection by blacks and Hispanics, all other cocaine injection, heavy use prior to entry into methadone treatment by blacks, and use of drugs in shooting galleries were independent predictors of HIV infection. Methadone therapy was associated with substantial reductions in heroin use and some reduction in cocaine use, but 24% of cocaine users receiving methadone began or increased cocaine injection after entry into treatment. PMID- 2909799 TI - Evaluation of potentially preventable deaths among pedestrian and bicyclist fatalities. AB - The prehospital, emergency department, and in-hospital care of 84 patients who died following a pedestrian- or bicycle-motor vehicle collision in a four-county area was retrospectively reviewed using a systematic, detailed scoring system. The purpose of the study was to examine the effectiveness of an advanced paramedic-regionalized trauma care system and to examine the usefulness of a systematic evaluation tool in identifying preventable and possibly preventable deaths. Among the 84 deaths, one was judged to be preventable and 18 possibly preventable. The one preventable death occurred in the emergency department, while the possibly preventable deaths more commonly occurred after 48 hours and were due to central nervous system injury, sepsis, and multiple organ failure. Prolonged prehospital and emergency department time and failure to establish an airway were the most common problems identified as contributing to fatal outcome. The use of explicit criteria was demonstrated to be an effective addition to the analysis of trauma care systems. PMID- 2909800 TI - Harmful genital care practices in children. A type of child abuse. AB - Little attention has been paid in the literature to children's genital hygiene in recent years. We describe harmful genital care practices that produce physical and/or psychoemotional abnormalities in children. These practices comprise unusual and ritualistic handling and inspection of the child's genitals. Abnormalities produced include chronic and varied somatic complaints and behavioral anomalies, changes in genital anatomy, unnecessary medical diagnostic and therapeutic interventions, and, sometimes, overt sexual abuse. The practices need to be recognized as harmful to children, and effective intervention must be sought. PMID- 2909801 TI - A piece of my mind. Prairie wedding. PMID- 2909802 TI - Needle localization in occult breast lesions. AB - A series of 211 women underwent 211 preoperative needle localizations of nonpalpable breast lesions. All mammographic, operative, and pathological data were reviewed. Carcinoma occurred in 10%. Seventeen (81%) were invasive, and four (19%) were noninvasive. Forty-three percent of the cancers were minimal carcinoma (in situ or an invasive cancer measuring less than 5 mm in size with negative axillary nodes), and 48% were less than 1 cm. Overall, metastasis to axillary lymph nodes occurred in 10%. The mammographic findings of microcalcifications occurred in 81% of the malignant group and in 33% of the benign group. The combination of microcalcifications in association with an irregular density was only found in the malignant group. We conclude that 1) needle localization enables the early detection of stage I breast carcinoma and 2) the mammographic findings of microcalcifications in association with an irregular density occur only with malignancy in this series. PMID- 2909803 TI - Surgical salvage for recurrent "early" glottic cancers. AB - A 25-year retrospective study of 143 early (T1 and T2 N0) glottic cancer, patients was done to determine the recurrence rate following initial radiation therapy, the surgical salvage rate, and incidence of cervical lymph node metastases. Radiation therapy gave a 5-year cure rate of 78% for stage I and 57% for stage II. Total laryngectomy for recurrent squamous cell carcinoma had a 5 year salvage rate of 66% for stage I and 61% for stage II recurrent tumors. The overall 5-year cure rate with initial and second therapy for stage I and stage II glottic cancers was 93% and 83%, respectively. PMID- 2909804 TI - Tumor tissue is more sensitive to mitomycin C, carboquone, and aclacinomycin A than is adjacent normal tissue in vitro. AB - In tissues obtained from patients undergoing gastrectomy or colectomy, sensitivity to mitomycin C (MMC), carboquone (CQ), and aclacinomycin A (ACR) was examined in 20 tumors (15 gastric, 5 colorectal) and in the adjacent normal mucosal tissues, using the in vitro succinate dehydrogenase inhibition test. The succinate dehydrogenase (SD) activity decreased to a greater extent in the tumor tissues than in adjacent normal tissues, at rates of 80% for MMC, 80% for CQ, and 90% for ACR. There were no correlations between SD activities of tumor and adjacent normal tissue, r = 0.157 for MMC, r = 0.435 for CQ, and r = 0.375 for ACR. Normal tissues were sensitive to MMC in 25% of cases sensitive to MMC in the tumor tissues, 46% for CQ, and 38% for ACR. These results show that the antitumor effects of MMC, CQ, and ACR are relatively specific for tumor tissues and that the assay of chemosensitivity of normal tissues is meaningful for predicting the toxic effects of antitumor drugs on these tissues. PMID- 2909805 TI - Leiomyosarcomas of the extremities. AB - Leiomyosarcomas are uncommon malignant neoplasms that rarely arise in the extremities. We report on the clinical characteristics of 17 cases seen at the Memorial Sloan-Kettering Cancer Center over a 32 year period. Most neoplasms occurred in the lower extremities, and most of the tumors recurred after surgery alone, with several late recurrences. The overall prognosis was grim, with a median survival of 24 months. More aggressive multidisciplinary approaches to this disease are warranted. PMID- 2909806 TI - Advanced basal cell carcinoma and successful treatment with chemotherapy. AB - The patient presented in this report has a large basal cell carcinoma on the wrist and thigh. The lesion on the wrist was nonresectable without amputation. The patient showed an impressive response to chemotherapy with systemic cyclophosphamide, adriamycin, and intra-arterial cisplatin. The tumor could be excised by a simple excision on both sites and showed no residual tumor on the hand and only a microscopic focus on the thigh. The patient continues to be free of disease 3 years after the initiation of the therapy. PMID- 2909807 TI - Myelodysplasia, chemical exposure, and other environmental factors. AB - This paper describes a case-control study of the occupational and environmental exposures of patients with myelodysplasia. The methodology, first described in Canada for solid tumors, estimates lifetime exposures to a number of potential toxic hazards or carcinogens. This pilot study confirms that the methodology, with the use of questionnaires and interviews, can estimate exposures to specific chemicals and shows some significant associations with myelodysplasia, including exposure to petrol or diesel compounds. PMID- 2909808 TI - Serum and urine glycosaminoglycans in myeloid leukemia and myelodysplasia. AB - Urinary glycosaminoglycan excretion is increased in a variety of human diseases, including malignancy. We have measured serum and urine glycosaminoglycan levels by the carbazole method of uronic acid determination in patients with myeloid leukemia or myelodysplasia. Eleven patients were studied during active disease as well as eight in complete remission. Serum levels in patients with active disease did not differ significantly from 11 healthy volunteers with no hematological disease. In contrast, the median urine level for the patients with active disease was 7.6 mg uronate/g Creatinine (Creat) compared to 2.6 for controls (p less than 0.002). Interestingly, the eight patients in complete remission also had a significant increase in uronate excretion with a median of 7.3 (p less than 0.002). These results suggest that elevated urinary glycosaminoglycan levels in leukemia are not due to impaired ability of the liver to clear circulating glycosaminoglycans or overproduction by leukemic cells. The observed increase in glycosaminoglycan excretion may be due to altered bone marrow matrix metabolism that is often not reversed by the achievement of hematologic remission. PMID- 2909809 TI - Cytogenetically unrelated clones in hematological neoplasms. AB - We have reviewed literature data on 6,306 cases of hematological neoplasia--acute and chronic lymphatic and myeloid leukemias (CML excepted), myelodysplastic and chronic lymphoproliferative and myeloproliferative disorders, and malignant lymphomas--with the goal of quantitatively ascertaining how often cytogenetically unrelated clones occur in these diseases. Unexpectedly wide variations were found: in ANLL, unrelated clones were present in 1.1% of the 2,506 known cases with chromosome abnormalities characterized with banding technique; in the various myelodysplastic (MDS) and chronic myeloproliferative (CMD) disorders (total number of cases 1,299) the frequency was 4.3% and in lymphatic malignancies 1.3% (total case number 2,501). In the latter group the proportions varied between 0.4% and 0.6% in ALL and malignant lymphoma (ML) to as much as 6.2% in CLD and 7.3% in CLL. Some karyotypic abnormalities were encountered more often than would be expected from their general frequency in the various diseases. This discrepancy was particularly evident in MDS and CMD, where 5q- was found in slightly less and +8 in somewhat more than half of the 56 cases. Furthermore, these two aberrations were found as the only changes in the two coexisting clones in one-fourth of the material. Although if viewed in isolation these data would undoubtedly be best explained by assuming a multicellular origin of the neoplasm, it is entirely possible that what are cytogenetically perceived as unrelated clones could be subclones with some invisible aberration in common. If so, this interpretation indicates that changes like +8 and 5q-, both of which are common rearrangements in bone marrow neoplasms, are actually secondary changes that develop during tumor progression. PMID- 2909810 TI - Distinct antigen expression related to DNA ploidy in a case of biphenotypic leukemia. AB - Three cell populations with different DNA indices were demonstrated in a case of biphenotypic terminal transferase (TdT)/myeloid-positive acute leukemia which had developed from a pre-leukemic diploid population also expressing biphenotypic features. At the time of development of acute leukemia, flow-cytometric analysis revealed expression of TdT by the diploid, the tetraploid, and the near-triploid cells, but only the tetraploid cells carried the myeloid-specific M2 antigen. Cytogenetic analysis showed four stemlines, diploid, tetraploid, tetraploid with del(2), and near-triploid with del(2) and variable chromosome losses. In vitro treatment with retinoic acid induced the expression of the M2 antigen by the diploid cells as well. This in vitro result is consistent with a myeloid differentiation commitment of the pluripotent leukemic stem cell. PMID- 2909811 TI - Human plasma thrombopoietin. PMID- 2909812 TI - Endoscopic paranasal sinus surgery: indications and considerations. AB - Recently, American otolaryngologists have become increasingly interested in endoscopic paranasal sinus surgery. This trend has been beneficial, because it has enhanced the understanding of the anatomy and pathophysiology of the sinuses. However, as with the introduction of any new surgical technique, it takes both time and experience to acquired the skills necessary to perform this procedure. To evaluate the state of endoscopic sinus surgery, we analyzed the experience of one of the authors with 100 consecutive patients undergoing therapeutic endoscopic sinus surgery over 23 months. With an average follow-up of 5 months (range: less than 1 month to 20 months), 14 patients had minor complications. The most common complication was synechia between the middle turbinate and the lateral nasal wall (six patients), resulting in revision surgery in four patients. Eighty-three patients were judged as having significantly improved after surgery, while ten were improved but had one episode of sinusitis postoperatively. The results of this series suggest that endoscopic paranasal sinus surgery is an efficacious advance in the treatment of sinusitis, given the limitations discussed in this report. PMID- 2909813 TI - A new needle and technique for MRI-guided aspiration cytology of the head and neck. PMID- 2909814 TI - An alternative to the transpalatal maxillary nerve block. PMID- 2909815 TI - Apneic anesthesia for laryngoscopy. PMID- 2909816 TI - Pyoderma gangrenosum involving the head and neck. PMID- 2909817 TI - Hemorrhagic tonsillitis. AB - Eleven patients with acute and/or chronic tonsillitis, who presented with a spontaneous tonsillar hemorrhage are reported and discussed. Two patterns of hemorrhage were noted: 1. diffuse, parenchymal bleeding and 2. localized bleeding from dilated surface vessels. Pharyngeal culture for group A beta-hemolytic Streptococcus was positive in six patients (55%). Monospot, heterophile antibodies, complete blood cell count, prothombin time, partial thromboplastin time, and viral studies did not consistently demonstrate any abnormality. Two patients, however, did have an elevation in liver enzymes. In five patients, the bleeding stopped spontaneously; in five patients the bleeding was controlled with local chemical cautery. In two patients, Avitene was used for hemostasis. One other patient's bleeding was controlled by electrocautery while the patient was under anesthesia for endoscopic evaluation of hemoptysis. Two patients required blood transfusions; one of these patients had a history of factor IX deficiency. Four case histories are discussed in detail to illustrate the varied clinical presentation and some pitfalls in diagnosing and managing this rarely reported complication of tonsillitis. Possible mechanisms for the pathophysiology include increased tonsillar blood flow, necrosis of tonsillar surface cells, and trauma to dilated surface vessels. No common bacterial or viral etiology could be determined in this rare, but potentially serious, complication of tonsillitis. PMID- 2909818 TI - Space-occupying orbital lesions: can critical increases in intraorbital pressure be predicted clinically? AB - Thirteen cadaver orbits were studied to determine whether noninvasive clinical measurements of globe excursion could be used to predict intraorbital pressure. Intraorbital pressure measurements, exophthalmometry, and orbitonometry (which measures resistance to globe retrodisplacement) were performed at 1-ml increments to 12 ml of added orbital volume. Orbitonometry, performed with forces of 100, 200, and 300 g, yielded both E (global position) and Y (retrodisplacement) values. Plots of orbital pressure against percentage of excursion, a function of orbital retrodisplacement (that is, orbital pressure versus [(E0 - E300)/E0] x 100), for 131 paired values over all orbits yielded a function with low percentage of excursion values associated with high intraorbital pressures. This relationship reflected both the proptosis and the increased orbital tension produced by added volumes. Comparison of clinical orbitonometry data with such experimental data may allow predictions about which patients are threatened by critical intraorbital pressure levels and may benefit from orbital decompression surgery to preserve vision. PMID- 2909819 TI - Facial nerve function following irradiated cable grafts. AB - Facial nerve cable grafting preceding postoperative radiation therapy in patients undergoing facial nerve resection for malignant disease remains controversial. Twelve cases of postoperatively irradiated facial nerve cable grafts are reviewed in detail. Of nine patients with long-term evaluations, all have shown some return of facial nerve function, with seven having moderate to excellent return of function, as documented on videotapes and shown in still photographs. We conclude that cable grafting is the treatment of choice, even though postoperative radiation therapy is planned. Cable grafting should almost always result in facial function that is clearly superior to the function provided by static or dynamic slings. PMID- 2909820 TI - Long-term follow-up and recent observations on 305 cases of orbital decompression for dysthyroid orbitopathy. AB - Dysthyroid exophthalmopathy (orbitopathy) results from an enlargement of extraglobal orbital structures, producing ocular proptosis, optic nerve compression, and corneal exposure. Treatment with corticosteroids and radiation may be beneficial; refractory cases require surgical decompression of the orbit. Transantral orbital decompression was described by Walsh and Ogura and has been performed in over 350 patients at this institution. A review of 305 patients with long-term follow-up was performed. Visual acuity improved or was maintained at preoperative levels in over 95% of the patients, with ocular recession ranging from 1 to 12 mm (average: 4 mm). Postoperative ocular balance of relative exophthalmos was to within 1 mm in 76% of the patients and to within 2 mm in approximately 90% of the patients. Normal postoperative extraocular muscle balance was present in 99 patients. Immediate postoperative diplopia was noted in 206 patients. Long-term follow-up revealed that in 137 of these patients, diplopia resolved or responded to conservative management. Extraocular muscle surgery was required for correction in 69 patients. Twenty-seven patients had postoperative complications. These included 16 patients with hypesthesia of the infraorbital nerve, 5 patients with sinusitis, 3 patients who had incomplete decompression, 2 patients with oral antral fistulae, and 1 patient who had CSF rhinorrhea. Five patients, despite surgery, radiation, and steroid therapy progressed to blindness. We conclude that this procedure is effective and carries few complications. Orbital imaging, using computed tomography or magnetic resonance sequence with reconstructive capabilities, permits early diagnosis and treatment of dysthyroid compression optic neuropathy. PMID- 2909821 TI - Injection of fat for soft tissue augmentation. AB - Perinephric rabbit fat was divided into small particles with scissors and razor blades and then injected subcutaneously into the donor rabbit. The injected fat was compared with surgically implanted fat. Subcutaneous augmentation with both types of fat resulted in similar findings. Grossly, 40% of injection and implantation sites were palpable after 16 to 36 weeks of observation. Histologically, fat was present at practically every site, but with a variable amount of fat cell destruction. This study demonstrates that the author's method for dividing and injecting fat produces comparable results in terms of soft tissue augmentation to those obtained by surgically implanting fat. Although injected fat does not fulfill the criteria as the ideal substance for soft tissue augmentation, fat injection may prove to be a clinically useful means for improving body contour. PMID- 2909822 TI - Chronic sinusitis and woodworking as risk factors for cancer of the maxillary sinus in northeast Japan. AB - In the period 1983 to 1985, 66 patients presented to six Japanese university hospitals with squamous cell carcinoma of the maxillary sinus. Using self administered questionnaires, a case-control study was conducted to examine history of nasal diseases, occupational exposures, and other possible risk factors for this disease. For each patient, two controls were selected from the general population, matched to the patient by sex, age (+/- 5 years), and district of residence. A history of chronic sinusitis was associated with a 2.3 fold increase in risk (p = 0.05). A high relative risk was also observed in males with an occupational history of woodworking or joinery, particularly when these jobs involved sanding or lathing practices (RR = 7.5, p = 0.02). No association between cigarette smoking and maxillary sinus cancer was observed in this study and no evidence was found that indoor air pollution in the home is involved in cancer development. PMID- 2909823 TI - Changes in pharyngeal properties after uvulopalatopharyngoplasty. AB - Uvulopalatopharyngoplasty is a commonly used modality for surgical treatment of snoring and obstructive sleep apnea. Although this procedure is thought to alter pharyngeal properties, its effect on pharyngeal mechanics has not been studied. The acoustic reflection technique was used to measure pharyngeal area at functional residual capacity and residual volume before and after uvulopalatopharyngoplasty in eight patients referred because of loud snoring. We also calculated the lung volume dependence of pharyngeal area, defined as the percent change in pharyngeal area between functional residual capacity and residual volume, normalized to the area at functional residual capacity. This parameter, which may be related to pharyngeal collapsibility, was obtained before and after uvulopalatopharyngoplasty. Preoperative sleep studies showed that one patient had obstructive sleep apnea (apnea index greater than 10). Uvulopalatopharyngoplasty resulted in a significant increase (p less than 0.01) in pharyngeal area (from 3.14 +/- 0.71 cm2 to 4.25 +/- 1.07 cm2) and residual volume (from 2.49 +/- 0.53 cm2 to 3.91 +/- 0.83 cm2). Following uvulopalatopharyngoplasty, the pharynx became stiffer, as manifested by a reduction in lung volume dependence of pharyngeal area from 19 +/- 12% to 8 +/- 13% (p less than 0.05). Six patients, including the patient with obstructive sleep apnea, reported improvement in snoring. Two patients reported worsening in snoring. One of the two was found to have reduction in pharyngeal area and lung volume dependence of pharyngeal area, and an increase in apnea index from 3 to 33. In selected snorers, uvulopalatopharyngoplasty results in improvement in snoring with a concomitant increase in pharyngeal area and a tendency toward lower pharyngeal collapsibility. PMID- 2909824 TI - Usher syndrome: an otoneurologic study. AB - Usher syndrome is an autosomal recessive disorder characterized by severe hearing loss or deafness and retinitis pigmentosa. Eleven families with 25 affected members were studied. The test battery included genetic studies, clinical examination, audiological, ophthalmologic, and otoneurological tests, and magnetic resonance imaging. Sixteen affected persons had profound hearing loss or were considered anacusic, with absent bilateral vestibular responses. These patients had varying degrees of retinitis pigmentosa. These 16 patients were considered to have type I Usher syndrome. Nine persons were diagnosed as Usher type II with a moderate to profound hearing loss, normal vestibular function, and retinitis pigmentosa of varying degree. Magnetic resonance imaging was normal in all cases. Otoneurological tests indicated no central nervous system disturbances. The conclusion is that hearing loss and balance problems in Usher syndrome are due to inner ear damage with no evidence of central nervous system disturbances. Furthermore, the ataxia seen in Usher type I is due to a combination of retinitis pigmentosa and bilateral peripheral vestibular deficiency. PMID- 2909825 TI - Congenital nasal pyriform aperture stenosis. AB - Congenital nasal pyriform aperture stenosis is an unusual and previously undescribed cause of nasal airway obstruction in the newborn. The nasal pyriform aperture is narrowed due to bony overgrowth of the nasal process of the maxilla. This anomaly may produce signs and symptoms of nasal airway obstruction in newborns and infants similar to those seen in bilateral posterior choanal atresia. Computed tomography confirms the diagnosis and delineates the anomaly. A series of six patients with nasal pyriform aperture stenosis is presented. Four patients were treated with surgical enlargement of the nasal pyriform aperture via a sublabial approach. One patient was repaired via a transnasal approach, and one patient did not undergo surgical intervention. Follow-up reveals normal nasal airway and facial growth in all patients. Mildly symptomatic patients with congenital nasal pyriform aperture stenosis may be treated expectantly, while severely symptomatic patients benefit from repair via the sublabial approach. PMID- 2909826 TI - The firing properties of second-order vestibular neurons in correlation with the far-field recorded vestibular-evoked response. AB - Action potentials of the second-order vestibular neurons of ten cats were recorded, both in rest and responding to sinusoidal and intense impulse acceleration stimuli. The data were compared with the far-field recorded vestibular-evoked response induced by the same impulse stimuli. It was found that the irregular (kinetic) neurons, which had a phase lead relative to head velocity, were capable of responding to these impulses with a latency as short as 3.5 msec after the start of head acceleration. It is assumed, therefore, that these neurons are the generators of the second wave of the vestibular-evoked response, having a similar latency. A high correlation was found between the latency of the first peak in the poststimulus time histogram in response to acceleration impulses and the phase of the response to sinusoidal rotations. The regular (tonic) vestibular neurons did not respond to acceleration impulses and probably did not contribute to the vestibular-evoked response. PMID- 2909827 TI - Homozygous hypobetalipoproteinemia with spared chylomicron formation. AB - Thirteen members of a family carrying a gene for pedigree of hypobetalipoproteinemia were analyzed for lipoprotein compositions, apolipoprotein (apo) B levels, and apo B isoforms. Judging from low density lipoprotein (LDL)-cholesterol (Chol) and apo B levels, a 75-year-old proband, a father who died of unknown fever, thrombopenia, and anemia, and his wife were heterozygous for hypobetalipoproteinemia. The proband had ataxic movement of hands and gait disturbance in later life. Three of four living siblings had extremely low levels of LDL-Chol (6 mg/dL) and LDL-apo B (2 mg/dL), and were postulated to have homozygous hypobetalipoproteinemia. Electrophoresis revealed marked deficiency of apo B-100, although trace amounts were noted in LDL. In contrast, apo B-48 was present in chylomicrons obtained after a fatty meal in the two patients with homozygous hypobetalipoproteinemia, indicating a selective deficiency of apo B-100 but not apo B-48. The defect in these patients seemingly is different from abnormal apo B-37 reported recently for a family with hypobetalipoproteinemia. Clinically, acanthocytotic red blood cells (8% to 12%), fatty liver, and low levels of serum lipid-soluble vitamins A and D were noted in homozygotes. One heterozygous sibling had 26 mg/dL LDL-Chol and 5 mg/dL LDL-apo B levels. All seven subjects in the third generation had low levels of Chol (85 to 140 mg/dL), LDL-Chol (40 to 63 mg/dL) and LDL-apo B (10 to 20 mg/dL). They also showed mild acanthocytosis (0.5% to 2%) and a decrease of fat-soluble vitamins in plasma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2909828 TI - Splanchnic and peripheral release of 3-methylhistidine in relation to its urinary excretion in human infection. AB - The present investigation was undertaken in order to determine the release of 3 methylhistidine (3MH) from the splanchnic region and from the leg, and the contributions these make to the increase in urinary 3MH excretion in infection. Thirteen febrile patients with infection were investigated. After an overnight fast, hepatic vein, femoral vein, and radial artery catheterizations were performed. Splanchnic and leg blood flows were determined by dye dilution technique. Plasma 3MH was analyzed by a modified HPLC method. The release of 3MH from the leg was 0.064 +/- 0.007 mumol/min (+/- SE) and from the splanchnic region 0.012 +/- 0.013 mumol/min. These releases of 3MH constitute 27% +/- 2% and 8% +/- 6% of the individual urinary excretions, respectively. With increasing degree of catabolism, measured as individual 3MH increase above baseline excretion or as the 3MH to creatinine ratio (3MH:Cr), the relative contribution to urinary excretion from the leg was increased (individual increase, P = 0.08; 3MH:Cr, P less than 0.01). Since this contribution was not decreased in the more catabolic patients, as would have been expected if the increase in urinary 3MH originated elsewhere, it is concluded that skeletal muscle is the source, and these results thus validate the use of urinary 3MH excretion as a marker of myofibrillar protein catabolism in infected patients. PMID- 2909829 TI - Heme inhibits cartilage metabolism and growth in vitro. AB - The present study was designed to investigate the potential role of heme as a direct inhibitor of cartilage metabolism and growth. We used the embryonic chick pelvic rudiment bioassays and the hypophysectomized rat cartilage sulfation bioassay, both sensitive to growth factors and growth inhibitors. In the chick bioassay pelvic rudiment growth was inhibited when heme was added to the culture medium at 0.1 mmol/L (after five days in culture, cartilage weight 224% +/- 11% of initial with normal serum, but 141% +/- 3% of initial with serum plus heme 0.25 mmol/L); the heme-induced growth inhibition was promptly reversible when cartilages were placed in heme-free medium. This was due, at least in part, to heme-induced inhibition of (1) [35S] sulfate incorporation into proteoglycans by as little as 0.05 mmol/L heme (66% +/- 5% of assay buffer); (2) [14C] leucine incorporation into proteins by greater than or equal to 0.05 mmol/L heme (85% +/- 6% of assay buffer); and (3) [3H] uridine incorporation by greater than or equal to 0.10 mmol/L heme (50% +/- 4% of assay buffer). In the rat cartilage sulfation bioassay (the literature "standard" bioassay for skeletal growth studies) a dose dependent inhibition of [35S] sulfate incorporation occurred with greater than or equal to 0.01 mmol/L added heme (82% +/- 3% of assay buffer). Heme caused a dose dependent and reversible inhibition of cartilage metabolism and growth, and it may have a novel role in the pathophysiology of growth retardation associated with some chronic disease. PMID- 2909830 TI - Hepatic metabolic alterations in rats treated with low-dose endotoxin and aspirin: an animal model of Reye's syndrome. AB - The administration of a sublethal dose of endotoxin (LPS) followed one hour later by a low dose of aspirin (LPS + ASA) to fasted rats leads to biochemical perturbations similar to Reye's syndrome. In this study hepatic energy metabolism was assessed in freeze-clamped liver samples (12 hours posttreatment) obtained from (250 to 300 g Sprague-Dawley) rats. The administration of aspirin alone to fasted rats did not significantly alter the hepatic levels of adenine nucleotides, total ketones, or acyl-CoA thioesters as compared to controls. In contrast, in both LPS and LPS + ASA samples, there were declines in ATP/ADP ratio (P less than .005), total ketones (P less than .001) and acetyl CoA (P less than .005) compared to their respective controls. A striking alteration in acyl-CoA thioesters was observed in LPS + ASA-treated animals. Unlike control, aspirin, or LPS-treated animals, LPS + ASA-treated animals accumulated relatively large amounts of unusual CoA esters, including propionyl-CoA, (iso)butyryl-CoA, beta methylcrotonyl-CoA, and isovaleryl-CoA, metabolites of the branch chain amino acid and odd-chain fatty acid oxidation pathways. The acyl-CoA profile is similar to that obtained in patients with Reye's syndrome. Like human patients with Reye's syndrome, these rats showed hyperammonemia, compromised fatty acid oxidation, and accumulation of branched chain amino acid oxidation metabolites. Accumulation of these intermediates with LPS + ASA is a possible mechanism for the potentiation of Reye's syndrome by aspirin. These findings provide biochemical evidence that sublethal doses of LPS + ASA administered to fasted rats produces an animal model of Reye's syndrome. PMID- 2909831 TI - Repeated ingestion of aspartame-sweetened beverage: effect on plasma amino acid concentrations in individuals heterozygous for phenylketonuria. AB - It has been suggested that excessive use of aspartame (APM) (N-L-alpha-aspartyl-L phenylalanine methyl ester) might grossly elevate plasma aspartate and phenylalanine concentrations in individuals heterozygous for phenylketonuria (PKUH). In study 1 six adult PKUH (three males; three females) ingested three successive 12-oz servings of beverage at 2-h intervals. The study was carried out in two parts in a randomized crossover design. In one arm the beverage was not sweetened. In the other the beverage provided 10 mg APM/kg body weight per serving. The addition of APM to the beverage did not significantly increase plasma aspartate concentration but did increase plasma phenylalanine levels 2.3 to 4.1 mumol/dL above baseline values 30 to 45 min after each dose. The high mean plasma phenylalanine level after repeated APM dosing (13.9 +/- 2.15 mumol/dL) was slightly, but not significantly, above the normal postprandial range for PKUH (12.6 +/- 2.11 mumol/dL). In study 2 six different adult PKUH ingested beverage providing 30 mg APM/kg body weight as a single bolus. The high mean plasma phenylalanine concentration and the phenylalanine to large neutral amino acid ratio were significantly higher when APM was ingested as a single bolus than when ingested as a divided dose. PMID- 2909833 TI - Differential catecholamine responses to dietary intake: effects of macronutrients on dopamine and epinephrine excretion in the rat. AB - Sympathetic nervous system (SNS) function responds to changes in diet in animals and humans; whether alterations in peripheral dopaminergic activity or in adrenal medullary secretion also occur with dietary manipulation is unclear. The present studies in rats demonstrate that casein supplementation of a lab chow diet raised urinary excretion of dopamine (DA) and epinephrine (E); both sucrose and lard feeding suppressed urinary DA, though only lard appeared to exert any effect on E excretion (reduction). Addition of tyrosine to the chow diet in an amount equivalent to the tyrosine content of casein increased DA output comparably to that seen in casein-fed rats, but did not reproduce the effects of casein on E excretion. Oral administration of carbidopa, an inhibitor of 3,4 dihydroxyphenylalanine (DOPA) decarboxylation in kidney reduced the DA response to casein, but chemical sympathectomy, which lowered urinary norepinephrine (NE), and adrenal denervation, which diminished E excretion, did not. Thus, the patterns of response of the peripheral dopaminergic system in kidney and of the adrenal medulla to short-term nutrient and tyrosine ingestion are distinct from those observed for the SNS and for each other, suggesting that all three peripheral catecholamine systems may be governed by separate regulatory mechanisms. PMID- 2909832 TI - Cystinuria in dogs: comparison of the cystinuric component of the Fanconi syndrome in basenji dogs to isolated cystinuria. AB - Two animal models for cystinuria have been examined: the Basenji dog with Fanconi syndrome and cystine stone-forming dogs of various breeds. Brush-border membranes were isolated from these animals and uptake of D-glucose and L-cystine was characterized. Experiments with isolated brush-border vesicles from Basenji dogs with cystinuria as a component of the Fanconi syndrome showed diminished sodium dependent D-glucose uptake but no decrease in L-cystine uptake even though the cystine defect in vivo was as high as 94% (ie, 6% reabsorption). In contrast, brush-border vesicles isolated from the kidney of a cystine stone-forming dog (Welsh Corgi) with a cystine defect of only 16% (ie, 84% reabsorption) had decreased uptake of cystine compared to values found for Beagle and Basenji vesicles. Thus, cystinuria found in Basenji dogs with the Fanconi syndrome differs from that in classic stone-forming cystinuric dogs. The alteration responsible for the cystinuria of Basenji dogs with Fanconi syndrome does not appear to have a membrane locus and may reflect altered energetics for transport, which are not detected in isolated vesicles. The cystine defect in cystinuric stone-forming dogs does appear to be reflected in the isolated membrane. PMID- 2909834 TI - Response to chest pain--why delayed? PMID- 2909835 TI - Ventilator-dependent children. AB - The issue of the ventilator-dependent child is a relatively-new one in Australia. Ventilator-dependent children pose complex and unique ethical, medical, economic and psychological problems. The experience of two Australian centres that are involved with the care of ventilator-dependent children is reported. Most of these children now are being cared for at home. Aspects of home care are outlined. After the initial period, the technical aspects are not a problem for most parents for whom the major issues are the provision and funding of nursing support. The complex ethical issues that are involved are discussed. It is concluded that undergoing ventilation at home rather than in a hospital appears to make the best of an otherwise almost-intolerable situation for ventilator dependent children, but that much more information is required about the outcome for these children and the long-term psychosocial impact of this treatment. PMID- 2909836 TI - Infant feeding--a clinical perspective. PMID- 2909837 TI - Familial colorectal cancer and the screening of family members. AB - A case-control study was undertaken of the family histories of colorectal cancer in 128 patients with colorectal cancers and those of 61 patients with colorectal adenomas and matched surgical control patients who were attending a regional surgical service in Western Australia. One family with multiple polyposis of the colon was excluded from the study. A history of colorectal cancer in one or more first-degree relatives was associated with a relative risk of colorectal cancer of 2.5 (95% confidence interval, 0.8 to 8.0), of adenoma of 2.0 (95% confidence interval, 0.5 to 8.0) and of any colorectal neoplasm of 2.3 (95% confidence interval, 0.9 to 5.6). Four patients with colorectal cancer and one patient with colorectal adenoma had more than one first-degree relative with colorectal cancer, whereas no control subject gave this history. The five families that were represented by these cases each showed some other features of non-polyposis familial colorectal cancer. It was estimated that familial factors could explain 60% of colorectal cancer in persons with a family history of the disease in a first-degree relative and 5% of colorectal cancer in the population as a whole. Haemoccult II tests were posted to 629 living first-degree relatives of the patients with colorectal cancers and adenomas; 44% of these relatives returned the completed tests. Four relatives with positive results of tests both before and after dietary restriction were investigated; all four subjects had colorectal adenomas. In addition, one subject had a short segment of ulcerative colitis. A further mailing of Haemoccult II tests one year later gave a 39% response rate; no further cases of colorectal neoplasia were found. One relative developed carcinoma of the caecum 10 months after a negative result in the first round of Haemoccult screening. Persons with two or more first-degree relatives with colorectal cancer, with or without other features of non-polyposis familial colorectal cancer, are at a high risk of the development of colorectal cancer. The comparatively-poor response to an offer of Haemoccult II testing and its known insensitivity and lack of specificity suggest that it is not a satisfactory method of screening these high-risk subjects. PMID- 2909838 TI - Long-term mechanical ventilation of patients in Australia. PMID- 2909839 TI - Tuberculous mastoiditis and laryngitis: a case report. AB - A case of miliary tuberculosis is presented. The patient was an Asian immigrant, and presented to hospital with acute mastoiditis with apparent secondary cerebellar abscess formation. He later developed laryngeal tuberculosis, which required a tracheostomy, and a cerebral tuberculoma. PMID- 2909840 TI - Nine-year survival in a case of untreated peritoneal mesothelioma. AB - A patient with malignant mesothelioma of the peritoneum, which has been untreated except for regular paracentesis for effusions, has remained alive and generally well for nine years. The poor prognosis that usually is ascribed to this disease may not be applicable universally. PMID- 2909842 TI - Ionizing x-radiation. PMID- 2909841 TI - The Nambour survey of skin cancer. PMID- 2909843 TI - Pre-eclampsia. PMID- 2909844 TI - Salmonellal arteritis. PMID- 2909845 TI - Perianal sepsis: drainage and fistulotomy or drainage only? PMID- 2909846 TI - Gonococcal conjunctivitis in Central Australia. PMID- 2909847 TI - Killing the dying. PMID- 2909848 TI - Chronic asthma. PMID- 2909849 TI - Attitudes to withdrawal bleeding. PMID- 2909850 TI - Availability of skull-base surgery in Australia. PMID- 2909851 TI - Cytotoxic-drug extravasation. PMID- 2909852 TI - Factors influencing prescribing. PMID- 2909853 TI - Mammography. PMID- 2909854 TI - Accuracy of mammography in an Australian community setting. PMID- 2909855 TI - Buspirone overdose. PMID- 2909856 TI - Dangers of illegible prescriptions. PMID- 2909857 TI - Ethics and drug trials. PMID- 2909858 TI - Time to lower cholesterol. PMID- 2909859 TI - Clomiphene citrate. PMID- 2909860 TI - The availability of heroin. PMID- 2909861 TI - Factors influencing the time from onset of chest pain to arrival at hospital. AB - One hundred patients who were admitted to a coronary-care unit were interviewed to determine the time interval from the onset of chest pain to their arrival at the Emergency Department of Royal Prince Alfred Hospital. Forty-nine per cent of patients took longer than two hours and 29% took longer than four hours to arrive at hospital; the patient who reported the longest time interval reached hospital 72 h after the onset of chest pain. Most of the delay between the onset of symptoms and arrival at hospital was a result of the time that the patients took to decide to seek medical attention. Once this decision was made, there was relatively-little delay before hospital presentation in patients who went directly to hospital. However, those patients who contacted a doctor rather than going directly to hospital took significantly longer to arrive at hospital, with a median total time to reach hospital of 212 min compared with 85 min for those who went directly to hospital (P = 0.002). Time delays of this magnitude compromise the efficacy of interventions such as thrombolytic therapy. There should be continuing public education to encourage patients with chest pain to seek early medical attention and, in metropolitan areas, patients with chest pain should be advised to proceed directly to hospital. PMID- 2909862 TI - Activation of mouse peritoneal macrophages by mannophosphoinositides of mycobacteria. AB - Peritoneal macrophages isolated from mannoside-methylated bovine serum albumin (MBSA)-immunized mice showed significantly enhanced phagocytosis of Mycobacterium smegmatis compared to control or MBSA-immunized groups. Immune macrophages also exhibited bacteriostatic activity against M. smegmatis. Pretreatment of mycobacteria with mannoside antibodies did not further alter the phagocytosis and bacteriostatic effect of immune macrophages. PMID- 2909863 TI - Intermediate adenovirus strains of subgenus D occur in extensive variety. AB - Eight intermediate adenovirus strains of seven serotypes, some of them related in their neutralizing or hemagglutinating antigens to new candidate serotypes, are presented in their serological properties and DNA fragment patterns with four endonucleases (BglII, BstEII, HindIII, SmaI). For characterization and strain comparison, an intensive serological identification is more meaningful than DNA restriction analysis. The intermediate strains were related in neutralization to types 28, 33, 37, 38, 44, or 46, in hemagglutination-inhibition to types 9, 13, 30, 45, or the hemagglutinin variant Hy. PMID- 2909864 TI - Molecular analysis of spontaneous and ethyl methanesulphonate-induced mutations of the hprt gene in hamster cells. AB - Independent spontaneous or ethyl methanesulphonate (EMS)-induced mutants lacking HPRT enzyme activity were analysed for changes in hprt gene structure. Of 21 spontaneous mutants, 6 had total gene deletions, 2 had partial gene deletions, and 13 were indistinguishable from wild-type by Southern analysis. In contrast a sample of 23 EMS-induced mutants, each of which showed potentially interesting characteristics (e.g. high reversion frequency, X-chromosome rearrangement), showed no detectable hprt gene changes. RNA isolated from 59 mutants with presumptive point mutations (13 spontaneous, 46 EMS-induced) was analysed on dot blots for changes in the amount of hprt mRNA. A wide range of mRNA levels was found, from mutants with undetectable amounts to those with more than wild-type amounts. However, Northern blots of all these mutant RNAs revealed only one (EMS induced) mutation with a change in hprt mRNA size. Taken with our previously published data on these mutants, it is argued that they represent a broad range of mutational types, and that the hprt gene mutation system provides a sensitive means of distinguishing mutational spectra of different DNA-damaging agents. PMID- 2909865 TI - Lethal and mutation frequency responses of Spiroplasma citri cells to UV irradiation. AB - The effect of UV irradiation on viability and mutant colony frequency in the Mollicute Spiroplasma citri was investigated at 3 phases of growth. The first UV induced mutants obtained in Mollicutes were selected: xylitol-resistant (XylR) and arsenic acid-resistant mutants (ArsR). Lethal and mutation frequency responses of S. citri cells increase with the age of the cell cultures. In all UV irradiated populations, light exposure slightly increases the number of survivors and decreases the induced mutation frequency; liquid holding conditions increase the number of both survivors and mutant colonies. This suggests that, in UV irradiated S. citri cells maintained under liquid holding conditions, there is no dark reactivation but induction of an error-prone repair system of the SOS type. In S. citri, the error-free light and dark repair systems are inefficient. Results allow the development of a method to select UV-induced mutations usable as markers in genetic studies of Spiroplasma cells. PMID- 2909866 TI - Long-term, low-dose benzo[a]pyrene-induced mutation in human lymphoblasts competent in xenobiotic metabolism. AB - We have studied the mutagenic effects of benzo[a]pyrene (BP) administered in a long-term, low-dose fashion to metabolically competent human lymphoblastoid cells. A continuous dose as low as 0.02 microM for 20 days produced a significant increase in mutant fraction at the 6TG-resistance (HGPRT) locus. The slope of the mutant fraction over time in the 0.02 microM BP-treated culture was twice that observed in the untreated concurrent control; 0.02 microM therefore represents the doubling dose of BP for gene mutation in this cell line. For higher doses of 0.1, 0.5 or 1 microM BP, the rate (or efficiency) of induced mutation was considerably higher for the first 5 or 6 days of exposure than for the last 14 15. This did not appear to be due to a growth disadvantage against early-arising mutants. Comparison to previously published data in the same cell system (Crespi and Thilly, 1984) revealed that the long-term , low-dose protocol (0-1 microM for up to 20 days) was significantly more efficient at inducing mutations than a short-term, high-dose protocol (0-10 microM for 1 day). PMID- 2909867 TI - Micronucleus formation in 2-cell embryos after in vitro X-irradiation of mouse spermatozoa. AB - Mouse spermatozoa were exposed in vitro to various X-ray doses and added to a medium containing superovulated oocytes. The percentage of fertilized oocytes was determined 24 h after sperm addition and 2-cell embryos were investigated for micronucleus formation. The fertilization rate was drastically decreased after exposure to 470 cGy whereas smaller doses had no effect. The dose-response relationship for micronucleus formation per embryo was linear-quadratic and the number of embryos with micronuclei increased linearly with dose. The distribution of micronuclei among 2-cell embryos showed a significant overdispersion relative to the Poisson distribution after sperm irradiation for doses above 188 cGy. PMID- 2909868 TI - Case-control cytogenetic study in offspring of mothers treated with bromocriptine during early pregnancy. AB - The distribution of modal and non-modal karyotypes was examined in mitoses of lymphocyte cultures of 31 children who had been exposed to bromocriptine in utero, and in 31 matched controls. No mosaicism was diagnosed. Furthermore, no more hypomodal cells occurred in the study group than in the control group. PMID- 2909869 TI - Repair capacity of fertilized mouse eggs for X-ray damage induced in sperm and mature oocytes. AB - To study the repair capacity of fertilized mouse eggs for X-ray damage induced in sperm and mature oocytes, the potentiating effects of 3 well-known repair inhibitors, arabinofuranosyl cytosine (ara-C), 3-aminobenzamide (3AB) and caffeine, on the frequency of induced chromosome aberrations were examined in eggs fertilized with X-irradiated sperm or in eggs irradiated with X-rays at the mature oocyte stage immediately before fertilization. Gametic treatment, fertilization and embryo culture were carried out in vitro. Ara-C treatment was done only in the pre-DNA replication period, while treatment with 3AB and caffeine was continuous from fertilization to the first-cleavage metaphase. The induction of chromosome aberrations by exposing sperm or oocytes to X-rays was remarkably potentiated by post-treatment incubation in the presence of each of the 3 inhibitors. This result indicates the possibility that X-ray damage induced in sperm or oocytes is reparable in the fertilized eggs and that various types of repair processes are involved. PMID- 2909870 TI - Constitutive heterochromatin polymorphism and chromosome damage in viral hepatitis. AB - The frequencies of chromosomal aberrations and sister-chromatid exchanges (SCEs) were scored in relation to constitutive heterochromatin in 100 patients with viral hepatitis B, 100 patients with viral hepatitis A and 100 age- and sex matched normal controls. 23.4%, 15% and 4% of the cells showed chromosomal aberrations in patients with hepatitis B, hepatitis A and normal controls respectively. Non-random involvement of chromosomal aberrations were also noted in chromosome 1 of patients with hepatitis B and A as compared to normal controls. The frequencies of SCEs (mean +/- S.D.) were found to be 10.40 +/- 2.83 in hepatitis B and 8.70 +/- 2.34 in hepatitis A. These values were significantly higher than the SCE frequency (mean +/- S.D.) of 5.88 +/- 2.25 observed in normal controls (P less than 0.001). The intra-chromosomal distribution of SCEs revealed a relatively increased incidence of SCEs in chromosome 1 of patients with hepatitis B and A as compared to normal controls. Analysis of constitutive heterochromatin polymorphism showed chromosome 1 qh+ to be the most frequent variant in patients with hepatitis B and A as compared to normal controls. The increased involvement of C-band variant 1 qh+ in patients with hepatitis B and A as compared to normal controls may indicate that extra heterochromatin offers additional sites for viral integration. PMID- 2909871 TI - Normal uracil-DNA glycosylase activity in Bloom's syndrome cells. AB - Cells from patients with Bloom's syndrome, a rare human disease with autosomal recessive mode of inheritance, exhibit cytological abnormalities involving DNA metabolism. Bloom's syndrome is characterized by a greatly increased cancer frequency which may reflect a specific defect in DNA repair and replication. Evidence has recently been presented of the existence in Bloom's syndrome of an abnormality of the DNA ligase involved in semiconservative DNA replication. Another abnormality, in the excision-repair pathway of Bloom's syndrome cells, is reportedly due to an aberrant immunological reactivity of the DNA-repair enzyme uracil-DNA glycosylase. In this investigation we show, however, that the catalytic activity of uracil-DNA glycosylase appears to be normal in Bloom's syndrome lymphoblastoid cells. PMID- 2909872 TI - Frequency and distribution of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced structural chromosome aberrations in fibroblasts from sarcoma and non-Hodgkin's lymphoma patients. AB - The frequency and distribution of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) induced structural aberrations, i.e., chromatid and chromosome gaps, breaks, and exchanges, were studied in fibroblasts from 16 patients with sarcoma, 15 with non Hodgkin's lymphoma (NHL), and 14 controls. The mean frequencies of aberrant cells, and gap, break, and gap + break events per 100 cells were 22.9, 5.1, 28.6, and 33.7 in the sarcoma group; 19.1, 5.0, 22.5, and 27.5 in the NHL group; and 23.5, 6.1, 33.5, and 39.6 in the control group. None of the differences between the groups were statistically significant. The distribution of MNNG-induced aberrations was non-random (P less than 0.001) in all 3 groups. Eight, 11, and 17 chromosome bands in the sarcoma, NHL, and control groups, respectively, were particularly break-prone. Only 2 hot spots in the sarcoma group (1p32, 11q23), and 3 in the NHL group (1p36, 3q25, 6p21), coincided with the 25 and 60 bands known to be involved in primary rearrangements in sarcomas and NHL. We conclude that neither the frequency nor the distribution of MNNG-induced chromosomal aberrations indicates any latent chromosomal instability in sarcoma and NHL patients. PMID- 2909873 TI - The pathophysiology of urinary incontinence among institutionalized elderly persons. AB - Although 1 million institutionalized elderly persons have urinary incontinence, little is known about the causes of this problem. We conducted clinical and physiologic studies to determine the causes of established incontinence in a representative sample of 605 institutionalized elderly persons (mean age, 89 years), of whom 40 percent were chronically incontinent of urine. Detailed urodynamic studies in 94 of the 245 incontinent patients (77 women and 17 men; 38 percent) showed that detrusor overactivity was the predominant cause in 61 percent, with concomitant impaired detrusor contractility present in half these patients. Other causes among women were stress incontinence (21 percent), underactive detrusor (8 percent), and outlet obstruction (4 percent). Among the relatively few men in this sample, outlet obstruction accounted for 29 percent of the cases. In 35 percent of the patients, at least two coexisting probable causes of incontinence were identified. Diagnoses among patients with impaired mobility or mentation differed little from those in unimpaired patients. We conclude that the pathophysiology of incontinence in this population is complex; that detrusor hyperreflexia with normal contractility ("uninhibited bladder") accounts for the minority of cases (29 percent), even among patients with dementia; and that the causes of incontinence are as diverse in severely impaired elderly persons as in those who are unimpaired. PMID- 2909874 TI - Thin-basement-membrane nephropathy in adults with persistent hematuria. AB - Thin-basement-membrane nephropathy, also called benign recurrent hematuria, is characterized by diffuse thinning of the glomerular basement membrane and by hematuria. To determine the incidence of thin-basement-membrane nephropathy among patients with idiopathic hematuria, we conducted a prospective study in the nephrology units of three large hospitals in the Netherlands. Eighty normotensive adults without azotemia underwent renal biopsy because of recurrent macroscopic hematuria (n = 26) or persistent microscopic hematuria (n = 54). Idiopathic IgA nephropathy was found in 27 of the 80 patients. Light microscopical examination showed that 42 patients had normal renal tissue. The remaining 11 patients had mesangioproliferative glomerulonephritis (n = 5), interstitial nephritis (n = 3), or focal global glomerulosclerosis (n = 3). Tissue from the 42 patients whose renal biopsy specimens were normal when examined with light microscopy was analyzed morphometrically with electron microscopy to determine the thickness of the glomerular basement membrane. Two subsets of patients were identified by this analysis. In 18, thin-basement-membrane nephropathy was found (mean basement membrane thickness [+/- SE], 191 +/- 28 nm; normal, 350 +/- 43 nm); all but one of these 18 patients had microscopic hematuria, which persisted during follow-up (median duration, 50 months). (Of the 54 patients who presented with microscopic hematuria, 17 [31 percent] had thin-basement-membrane nephropathy.) The thickness of the glomerular basement membrane was normal in the other 24 patients (361 +/- 69 nm); during follow-up, hematuria disappeared in all 13 of these patients who had macroscopic hematuria, and hematuria resolved in 5 of the 11 patients who had microscopic hematuria. We conclude that in patients with persistent microscopic hematuria, the incidence of thin-basement-membrane nephropathy is similar to that of idiopathic IgA nephropathy. Morphometric analysis of the thickness of the glomerular basement membrane should be included in the workup of adults with persistent microscopic hematuria that is not of urologic origin. PMID- 2909875 TI - Malformations due to presumed spontaneous mutations in newborn infants. AB - We conducted hospital-based surveillance of congenital malformations to determine the rate of apparently spontaneous single mutations leading to recognized phenotypes. Through surveillance of 69,277 infants with gestational ages of at least 20 weeks, we identified 48 infants (0.07 percent) with major malformations, with phenotypes that suggested that the malformations were due to single mutant genes. Family studies suggested that 11 of these infants (10 with autosomal dominant disorders and 1 with an X-linked condition) were affected as the result of a new (spontaneous) genetic mutation. The spontaneous mutation rates per gene were 0.7 x 10(-5) and 1.44 x 10(-5) for the disorders in which one and two infants were affected, respectively. In addition, 5 of the 10 infants with autosomal recessive malformations had negative family histories, but we were unable to infer the presence of spontaneous mutations in these cases. Because the family history was negative in 44.4 percent of the infants with disorders considered due to autosomal or X-linked genes, counseling should include the understanding that genetic disorders often occur unexpectedly among children of healthy parents. PMID- 2909876 TI - Treatment of diversion colitis with short-chain-fatty acid irrigation. AB - A condition known as diversion colitis frequently develops in segments of the colorectum after surgical diversion of the fecal stream; it persists indefinitely unless the excluded segment is reanastomosed. The disease is characterized by bleeding from inflamed colonic mucosa that mimics the bleeding of idiopathic inflammatory bowel disease, and it may culminate in stricture formation. We hypothesized that this condition is caused by the absence of luminal short-chain fatty acids, the preferred metabolic substrates of colonic epithelium. We studied four patients with diversion colitis, none of whom had evidence of Crohn's, idiopathic ulcerative, or infectious colitis. The excluded segment of the rectosigmoid contained negligible concentrations of short-chain fatty acids. When D-glucose was instilled, it did not undergo appreciable anaerobic fermentation. Instillation of a solution containing short-chain fatty acids twice daily resulted in the disappearance of symptoms and the inflammatory changes observed at endoscopy, over a period of four to six weeks. Remission has been maintained for up to 14 months (in one patient) by instillation daily to twice weekly. Administering enemas containing isotonic saline, or omitting treatment for periods of two to four weeks during the regimen, by contrast, did not produce any improvement or rapid relapse of the colitis. Histologic observation revealed a distinctive type of mucosal inflammation that resolved more slowly and less completely than the gross appearance of the inflamed mucosa. From these preliminary studies we infer that diversion colitis may represent an inflammatory state resulting from a nutritional deficiency in the lumen of the colonic epithelium, which is effectively treated by local application of short-chain fatty acids, the missing nutrients. PMID- 2909877 TI - Through thick and thin. PMID- 2909878 TI - Continuous improvement as an ideal in health care. PMID- 2909879 TI - Fraud in biomedical research. PMID- 2909880 TI - Pathogenesis of diabetic neuropathy. PMID- 2909881 TI - Direct visualization of mycobacteria in blood culture. PMID- 2909882 TI - Inadequacy of current labeling of nonophthalmic drops. PMID- 2909883 TI - Recurrent syphilitic uveitis. PMID- 2909884 TI - Brain donation. PMID- 2909886 TI - History of 'biotechnology'. PMID- 2909885 TI - Waiting for the amniocentesis. PMID- 2909887 TI - Primer availability. PMID- 2909888 TI - Splicing a spliceosomal RNA. PMID- 2909889 TI - Sickle cell anaemia. A simple disease with no cure. PMID- 2909890 TI - Seal vaccination success. PMID- 2909891 TI - Female transfer and inbreeding avoidance in social mammals. AB - In most social mammals, males leave their natal group to breed in other groups whereas females commonly remain in the same group throughout their lives. In a few species however, females usually transfer between groups during adolescence. The functional significance of sex differences in dispersal and their connection, if any, to the avoidance of inbreeding is disputed. Here I show that in polygynous mammals where females commonly remain to breed in their natal group, their average age at first conception typically exceeds the average period of residence of adult males in breeding groups. In contrast, where females usually transfer to breed in other groups, the average residence of breeding males or of resident male kin groups typically exceeds the average age of females at first conception. These results support the suggestion that female mammals commonly transfer to avoid inbreeding with their father or other close relatives, although female dispersal may also occur for other reasons. PMID- 2909892 TI - Duchenne muscular dystrophy gene product is not identical in muscle and brain. AB - Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder resulting in progressive degeneration of the muscle. It affects about 1 in 3,500 male children. Becker's muscular dystrophy is a less severe disease allelic to DMD. Some 30% of DMD patients suffer from various degrees of mental retardation. The giant DMD gene spans about 2,000 kilobases and codes for a 14-kilobase messenger RNA and a protein of molecular weight 427,000. DMD mRNA is most abundant in skeletal and cardiac muscle and less so in smooth muscle. We reported that the expression of the gene is developmentally regulated during the differentiation of primary muscle cultures and in myogenic cell lines in a way similar to the expression of muscle-specific genes such as myosin light chain 2 and skeletal muscle actin. Similar results have been obtained with human primary myogenic cells. Significant levels of DMD mRNA are found in brain tissue. Here we show that the transcript of the DMD gene and the amino terminal of the encoded protein differ in brain and muscle. The 5' ends of these mRNA species are derived from different exons. The results suggest that the two mRNA types are transcribed from different promoters. PMID- 2909893 TI - The pseudoautosomal boundary in man is defined by an Alu repeat sequence inserted on the Y chromosome. AB - The Y chromosome, which in man determines the male sex, is composed of two functionally distinct regions. The pseudoautosomal region is shared between the X and Y chromosome and is probably required for the correct segregation of the sex chromosomes during male meiosis. The second region includes the sex-determining gene(s), the presence of which is necessary for the development of testes. The two regions have contrasting genetic properties: the pseudoautosomal region recombines between the X and Y chromosome; the Y-specific region must avoid recombination otherwise the chromosomal basis of sex-determination breaks down. The pseudoautosomal region is bounded at the distal end by the telomere and at the proximal end by X- and Y-specific DNA. We have found that the proximal boundary was formed by the insertion of an Alu sequence on the Y chromosome early in the primate lineage. Proximal to the Alu insertion there is a small region where similarity between the X and Y chromosomes is reduced and which is no longer subject to recombination. PMID- 2909894 TI - The gene for the U6 small nuclear RNA in fission yeast has an intron. AB - The small nuclear RNAs (snRNAs) are a class of metabolically stable small RNAs present in the nuclei of eukaryotic cells. In mammalian cells, there are six major molecular species (U1 to U6 snRNA), which are complexed with proteins, forming small nuclear ribonucleoprotein particles, snRNPs. Of these, the U1, U2, U4, U5, U6 snRNPs are thought to participate in pre-mRNA splicing as part of the spliceosome. Here, we describe the characterization of the gene coding for the Schizosaccharomyces pombe U6 snRNA. Unexpectedly, the Schiz. pombe U6 RNA gene was found to contain an intron-like sequence of 50 base pairs. Northern blot analysis and RNA sequencing revealed that this intron-like sequence is precisely removed from the transcript. The mature U6 RNA of Schiz. pombe has 77% sequence homology with the mammalian U6 RNA. In Schiz. pombe, it is possible that U6 RNA is not only involved in pre-mRNA splicing, but is also a splicing substrate. This is the first report of an intron in a snRNA gene. PMID- 2909895 TI - Structure of the membrane-pore-forming fragment of colicin A. AB - Colicins are antibiotic proteins produced by and active against sensitive Escherichia coli and closely related bacteria. They can adsorb to specific receptors located at the external surface of the outer membrane of sensitive cells, and are then translocated to their specific targets within these cells. The largest group of colicins comprises those which can form voltage-dependent channels in membranes, thereby destroying the cell's energy potential. Colicin molecules are organized in structural domains, each domain carrying one function associated with the toxin's lethal activity. The pore-forming activity seems to be located at the carboxyl terminus. A thermolytic fragment comprising amino acids 389-592 from colicin A has pore-forming properties very similar to those of the entire molecule. This fragment is soluble in aqueous medium and spontaneously inserts into lipid bilayers. We have determined the structure of the pore-forming fragment of colicin A by X-ray crystallography and refinement at 2.5 A resolution. The protein consists of ten alpha-helices organized in a three-layer structure. Two of the helices are completely buried within the structure and form a hydrophobic hairpin loop similar to that proposed for signal sequences which function in translocation. We present a model for insertion of the protein into lipid bilayers the features of which may be applicable in other biological systems involving protein insertion or translocation across membranes. PMID- 2909896 TI - Evaluation of thermography in the diagnosis of selected entrapment neuropathies. AB - We studied 20 normal subjects, 22 patients with carpal tunnel syndrome, and 15 with ulnar neuropathy at the elbow to compare the diagnostic accuracy of infrared thermography with that of conventional electrodiagnostic studies. We found abnormal thermograms in 55% of patients with carpal tunnel syndrome and 47% with ulnar neuropathy, using 2.5 SD from the normal mean as criteria for abnormality. The abnormalities consisted of either an increase in interside temperature difference in the fingers and hands or an alteration of the normal thenar hypothenar temperature gradient in the fingers. The sensitivity of thermography was considerably lower than that of conventional electrodiagnostic methods. Moreover, the thermographic abnormalities were nonspecific, and could be misleading as they did not reliably identify the side of lesion or distinguish between median or ulnar nerve involvement. Thus, thermography is not helpful in the diagnosis of these two common entrapment neuropathies. PMID- 2909897 TI - Post-traumatic tremor. AB - We present seven cases of tremor caused by mild head injury without loss of consciousness. The interval between head trauma to onset of symptoms was 1 to 4 weeks. A posture and kinetic tremor of the hands and head occurred unassociated with other neurologic signs. Myoclonic-like jerking was frequently present. Neuroimaging studies were normal. Clonazepam administration resulted in tremor reduction in three patients and propranolol decreased tremor in one patient. A tremor, similar to essential tremor, can be a rare complication of head trauma. PMID- 2909898 TI - Is ischemia implicated in chronic multifocal demyelinating neuropathy? AB - We describe a patient with chronic multifocal demyelinating neuropathy associated with persistent conduction block. Multifascicular lesions in sural nerve included a complete loss of myelinated fibers, demyelination, remyelination, onion bulb formation, and axonal attenuation. On the basis of these morphometric results we hypothesize that nerve ischemia may be involved in the pathogenesis of chronic multifocal demyelinating neuropathy. PMID- 2909899 TI - Guidelines on the vegetative state: commentary on the American Academy of Neurology statement. PMID- 2909900 TI - Position of the American Academy of Neurology on certain aspects of the care and management of the persistent vegetative state patient. Adopted by the Executive Board, American Academy of Neurology, April 21, 1988, Cincinnati, Ohio. PMID- 2909901 TI - Neurologic fragments. II. Remarks on anosognosia, confabulation, memory, and other topics; and an appendix on self-observation. AB - This is an account of an informal presentation of personal views and opinions concerning behavioral phenomena--anosognosia, confabulation, memory and amnesia, perseveration and agitation, plus a few interesting brief case histories that make a neurologic point. Finally, the practice of self-observation is recommended for neurologists, and a few examples from personal experience are described. PMID- 2909902 TI - Seizures in progressive supranuclear palsy. AB - Among 62 patients with progressive supranuclear palsy (PSP) seen over a 9-year period, we encountered seven who had seizure phenomena. We suggest that PSP patients have seizures more frequently than has been appreciated. PMID- 2909903 TI - Monozygotic twins concordant for the narcoleptic syndrome. AB - We report the first documented monozygotic twins who both had the narcoleptic syndrome. We assessed monozygosity by HLA antigens and by blood groups. In contrast to virtually all other narcoleptics, they had HLA-DQ1 instead of HLA DR2; this helped to localize the gene, and perhaps explains its greater expressivity in these than in other twins. PMID- 2909904 TI - Usefulness of a writing aid in writer's cramp. PMID- 2909905 TI - Spasm of the near reflex associated with metabolic encephalopathy. PMID- 2909906 TI - Swinging flashlight test. PMID- 2909907 TI - Alpha coma with sedative overdose. PMID- 2909908 TI - Stroke in patients with fusiform vertebrobasilar aneurysms. AB - We studied seven patients with brainstem infarction and large fusiform vertebrobasilar (VB) aneurysms to clarify the clinical, radiologic, and pathologic features. All presented with pontine infarcts; one also had a cerebellar infarct. VB TIAs preceded brainstem infarction in four patients. Angiography and CT documented VB fusiform aneurysmal dilatation. Four had intraluminal thrombi and one had severe basilar artery stenosis. Two distinct clinical pictures emerged: unilateral pontine infarcts with favorable outcome, presumably related to obstruction of a pontine penetrating artery at its origin from the posterior wall of the aneurysmal basilar artery, and major fatal bilateral pontine infarcts from basilar artery occlusion. Two patients came to autopsy. One had thrombus in the dilated basilar artery and a posterior cerebral artery branch embolus with hemorrhagic occipital infarction; the other had basilar artery thrombus with aneurysmal rupture and subarachnoid hemorrhage. Fusiform VB aneurysms caused brainstem stroke by intraluminal thrombus, local embolism, atherostenosis, and obstruction of paramedian penetrating arteries. Subarachnoid hemorrhage is an uncommon complication. PMID- 2909909 TI - Bilateral infarction of the medullary pyramids in humans. AB - We report the detailed clinical and pathologic account of a patient with an ischemic infarction restricted to both medullary pyramids. Although prevailing neurophysiologic teachings would predict a flaccid paralysis, the patient's pure motor quadriplegia was eventually associated with spasticity. PMID- 2909910 TI - Orthostatic hypotension as a risk factor for symptomatic occlusive cerebrovascular disease. AB - Thirteen patients presented with brief, repetitive, stereotyped transient ischemic attacks, large artery atherostenoses or occlusions with impaired collateral flow to a cortical perfusion borderzone, and orthostatic hypotension (OH). OH was caused by diabetes mellitus, aging, and treatments for ischemic heart disease and hypertension. Medical management of OH often eliminated the need for stroke prevention measures such as surgery or anticoagulation. Focal cerebral hypoperfusion from the combination of occlusive vascular disease and OH may be an underreported, treatable cause of TIA and stroke. PMID- 2909911 TI - Sympathotonic orthostatic hypotension: a report of four cases. AB - We describe four patients with sympathotonic orthostatic hypotension, a syndrome in which the decrease in blood pressure associated with standing is accompanied by tachycardia. The patients in this series had experienced either a viral infection or rapid weight loss prior to the onset of their orthostatic intolerance. Vasomotor reflexes and norepinephrine production were normal, and analysis of palmar autonomic surface potentials indicated that the sympathetic innervation of the upper extremities was intact. The amplitudes of the plantar autonomic surface potentials, however, were decreased although still within the normal range. The latencies of plantar autonomic surface potentials were slightly prolonged. Although most autonomic function tests are normal in sympathotonic orthostatic hypotension, mild abnormalities in the plantar autonomic surface potentials may indicate a neuropathy that primarily affects low thoracic or lumbar sympathetic neurons. PMID- 2909912 TI - CSF acetylcholinesterase levels are reduced in multiple system atrophy with autonomic failure. AB - Diminished CSF levels of acetylcholinesterase in patients with multiple system atrophy attended by autonomic failure suggest that CNS cholinergic involvement may occur in this disorder. The lack of correlation between the low enzyme levels and low CSF levels of monoamine metabolites in these patients indicates that the acetylcholinesterase reduction is not directly related to disruption in these neurotransmitter systems. Normal CSF acetylcholinesterase levels in those patients with pure autonomic failure are consistent with functional integrity of central cholinergic pathways and support a pathophysiologic involvement limited to the peripheral nervous system. PMID- 2909913 TI - Tumor-associated aphasia in left hemisphere primary brain tumors: the importance of age and tumor grade. AB - Although one-quarter of patients with primary brain tumors have language disturbances at the time of initial presentation, the factors contributing to their aphasia are not clear. A group of 32 patients with primary tumors of the left hemisphere was collected retrospectively and the relationship between clinical, radiographic, and pathologic factors and tumor-associated aphasia was examined. We assessed language function before beginning any treatment including steroids. The factor that best predicted language disturbance was greater patient age; the only other significant factor was tumor grade. Tumor size made a nearly significant impact, but tumor location within the left hemisphere did not correlate with aphasia. PMID- 2909914 TI - Left precentral gyrus and Broca's aphasia: a clinicopathologic study. AB - We describe an autopsied case in which a circumscribed lesion involving the left precentral gyrus caused mild but lasting Broca's aphasia. The patient developed nonfluent speech and writing disturbances (consistent with mild Broca's aphasia) following malignant lymphoma of the brain. After subtotal resection of the tumor and whole brain irradiation, his language disturbances continued without remarkable change for 3 years until his death. A neuropathologic study indicated that the lesion responsible for the patient's aphasia was restricted to the lower one-third of the precentral gyrus in the left hemisphere. As for the relationship between the left precentral gyrus and Broca's aphasia and its allied syndrome (ie, aphemia), we concluded that in Broca's aphasia the lower part of the precentral gyrus plays a more important role than previously assumed. PMID- 2909915 TI - Thalamic dementia and motor neuron disease. AB - A 46-year-old woman developed a progressive neurologic disorder over the course of 30 months which was characterized by profound dementia complicated by a motor neuron disorder that became evident 10 months prior to death. Postmortem examination of the nervous system disclosed extensive neuronal loss and gliosis of the thalamus, predominantly involving the dorsomedial nuclei, as well as severe degeneration of the corticospinal tracts, spinal anterior horns, and hypoglossal nuclei. The disease could not be transmitted to experimental animals by intracerebral inoculation of the patient's brain tissue. This case represents a unique dementing disorder, possibly familial, with associated motor neuron disease. PMID- 2909916 TI - Deficiency of pyruvate dehydrogenase complex (PDHC) in Leigh's disease fibroblasts: an abnormality in lipoamide dehydrogenase affecting PDHC activation. AB - Several groups have reported abnormalities of the pyruvate dehydrogenase complex (PDHC) in cultured cells or other tissues from patients with Leigh's disease (subacute necrotizing encephalomyelopathy). We therefore undertook studies to elucidate the molecular basis of the defect of PDHC in cultured skin fibroblasts from two patients with Leigh's disease. The deficit of total PDHC activity in homogenates of Leigh's disease fibroblasts could be restored by adding exogenous lipoamide dehydrogenase (LAD, E3), the third component of PDHC. The LAD in these Leigh's disease cells had a markedly reduced ability (less than 20% of normal LAD) to reconstitute with other PDHC components to form active enzyme complex. A polyclonal antibody to pig heart LAD inhibited LAD activity in control cells more efficiently than in Leigh's disease cells. Other mitochondrial enzyme activities and growth of these two Leigh's disease cells appeared normal. These results suggest that the deficiency of PDHC in these two patients with Leigh's disease was due to a structural abnormality of the LAD component of PDHC. PMID- 2909917 TI - Reciprocal inhibition in patients with hand cramps. AB - We studied inhibition of median nerve H-reflex produced by radial nerve stimulation in both arms of 14 patients with hand cramps and 15 normal volunteers. Median nerve stimulation was delivered 1 and 0.5 msec before and 0, 0.5, 1, 2, 10, 20, 30, 50, 75, 100, 200, 500, and 1,000 msec after radial nerve stimulation. Recordings were from surface electrodes positioned over flexor carpi radialis. We identified three periods of attenuation of median nerve H-reflex amplitude in the control group. When radial nerve conditioning stimuli were delivered simultaneously, 10 and 75 msec before median nerve test stimuli, H reflex amplitude diminished to 47%, 61%, and 69%. In the patient group we also found three periods of attenuation at the same delays, but the amount of attenuation was significantly less than in controls. Dividing the patients into two groups, dystonic hand cramp and simple hand cramp, both showed less inhibition than the control group, but the abnormality was greater in the dystonic cramp group. This test is the first to demonstrate physiologic disturbance in patients with hand cramps. PMID- 2909918 TI - The rostral basilar artery syndrome: diagnosis, etiology, prognosis. AB - Vascular occlusive disease of the rostral basilar artery (RBAS) causes a myriad of clinical signs and symptoms reflecting rostral brainstem-diencephalic and posterior hemispheric dysfunction. To help define the clinical profile, we prospectively studied 61 patients with clinical/neuroimaging evidence of RBAS during a 7-year period. Fourteen patients mirrored classic descriptions: severe visual, oculomotor and behavioral signs without prominent motoric dysfunction, uniformly poor prognosis, and intimate association with hypertension and prior episodes of vertebrobasilar ischemia (VBI). In contrast, 47 individuals had a reversible syndrome with excellent short-term functional recoveries, and were distinguished by a lower frequency and severity of hypertension, a greater incidence of arrhythmias in the young, and no history of VBI. All patients had important neurobehavioral abnormalities including an invariable acute confusional state. Diagnosis required the integrated assessment of neurobehavioral, ophthalmologic, and imaging tests. The clinical syndrome is more common and etiologically diverse than previously reported and is frequently unrecognized in the young and elderly who present with acute confusion. PMID- 2909919 TI - Experimental meningeal carcinomatosis selectively depresses local cerebral glucose utilization in rat brain. AB - Using quantitative autoradiography, we investigated the effect of meningeal carcinomatosis on local cerebral glucose utilization (LCGU). A rat model of meningeal carcinomatosis using Walker 256 tumor was used. LCGU was evaluated using 14C-2-deoxy-D-glucose according to the Sokoloff method. Thirty-one neuroanatomic structures were evaluated, both separately and as part of five functional or neuroanatomic groups: olfactory, auditory, visual, limbic, and white matter. The relationship between tumor and LCGU of underlying brain was examined. Compared with controls, there was no global change of LCGU in the experimental group that applied to all structures. However, mean LCGU was significantly depressed in olfactory cortex, temporal cortex, olfactory tubercle, amygdala, caudate/putaman, inferior colliculus, medial geniculate, anterior commissure, and corpus callosum, and the functional groups that make up the olfactory and auditory systems. There was no correlation between extent of regional tumor burden and degree of depression of LCGU in underlying structures. In meningeal carcinomatosis, tumor results in selective regional depression of LCGU. This occurs both in structures underlying tumor and those anatomically remote, but in certain cases, functionally related to structures subadjacent to tumor. These data may help to explain the diversity of neurologic dysfunction seen in patients with meningeal cancer. PMID- 2909921 TI - AIDS update--a roundup of news and trends. PMID- 2909922 TI - The day I "quit" nursing. PMID- 2909920 TI - Short-term outcomes of skull fracture: a population-based study of survival and neurologic complications. AB - All Olmsted County, Minnesota, residents who experienced brain injury from 1935 through 1979 were identified and their medical records reviewed for survival and neurologic outcome. Minimum inclusion criteria included loss of consciousness or post-traumatic amnesia or neurologic evidence of brain injury or skull fracture. Of 4,660 cases identified, skull fractures were observed in 28%. Over half of brain-injured patients who died did so within 24 hours of trauma; among 1-day survivors, subsequent survival was moderately impaired, especially in older individuals. Mortality was lowest in subjects without a skull fracture and increased with fracture severity. Associated neurologic injuries, complications, and deficits were generally more common in patients with skull fracture than those without and were much more frequent with more severe skull fractures. The types of neurologic deficits differed little between those with and without fractures, except that subjects with complicated skull fractures had higher proportions of special sensory deficits and multiple deficits. PMID- 2909923 TI - "Please let me go". PMID- 2909924 TI - Helping Scotty live on. PMID- 2909925 TI - Myths and facts about burns. PMID- 2909926 TI - Action stat! Ruptured bladder. PMID- 2909927 TI - Performing CPR on adults. PMID- 2909928 TI - Today's poisons--how to keep them from killing your patients. PMID- 2909929 TI - Septic shock--how to detect it early (continuing education credit). PMID- 2909930 TI - My most unforgettable patient. Darlene's legacy. PMID- 2909931 TI - Pregnant? Take these precautions. PMID- 2909932 TI - Whatever happened to the right to refuse treatment? PMID- 2909933 TI - A new program for reducing patient falls. PMID- 2909934 TI - A question of privacy. Should you protect a patient from himself? Ethics grand rounds. PMID- 2909935 TI - "How do I ask?" Requesting tissue or organ donations from bereaved families. PMID- 2909936 TI - Breaking the vicious circle of noncompliance. PMID- 2909937 TI - Brush up on antibacterial agents. PMID- 2909938 TI - An in-depth look at deep vein thrombosis. PMID- 2909939 TI - Dealing with demanding patients. PMID- 2909941 TI - A reasonable alternative ... RCTs ... no, thank you! PMID- 2909940 TI - A more acceptable solution. PMID- 2909942 TI - Nurse's failure to follow physician's orders. PMID- 2909943 TI - Just what are doctors' orders, anyway? PMID- 2909944 TI - The economic impact of universal precautions on a surgical unit. PMID- 2909945 TI - Allocating nursing resources in ambulatory care. PMID- 2909946 TI - Documentation: communicating professionalism. PMID- 2909947 TI - They shoot horses don't they? PMID- 2909948 TI - The hospital as wellness educator. PMID- 2909949 TI - Implementation of a skin care committee. PMID- 2909951 TI - Guidelines for management of two problems in home healthcare to ensure nursing care--effective at a better price. PMID- 2909950 TI - Nurse-to-nurse staff development. PMID- 2909952 TI - The economics of comparable worth. PMID- 2909953 TI - Role of the staff nurse in developing clinical policy. PMID- 2909954 TI - Rehabilitative care: who teaches paraprofessionals? PMID- 2909955 TI - A pressure sore task force. PMID- 2909956 TI - Surfactant replacement therapy: impact on hospital charges for premature infants with respiratory distress syndrome. AB - Surfactant replacement therapy for neonatal respiratory distress syndrome has the potential to reduce morbidity and mortality of very premature infants. To investigate whether surfactant replacement therapy will also reduce hospital charges for these infants, we compared the hospital charges incurred by a group of patients treated with surfactant with charges of control patients. Mortality in the surfactant-treated group (8%) was significantly decreased compared with the control patients (29%). Average daily hospital charges in the surfactant treated patients were 25% less than for the control patients. Most of the savings in daily hospital charges were due to a 52% reduction in daily charges for laboratory, x-ray, respiratory therapy, and other ancillary services. Similarly, ancillary charges for the first full week of hospitalization were significantly reduced by $1,883 for patients who received surfactant therapy. Analysis of the charges for the entire hospitalization revealed that surfactant-treated patients had a significantly smaller proportion of their charges that resulted from ancillary services and an increased proportion due to room charges. The average total hospital charges for the two groups were similar, but the total hospital charges to produce a surviving infant were $18,500 less in the surfactant-treated group than the charges to produce a survivor from the control group. It is likely that, in addition to a reduction in neonatal mortality and morbidity from respiratory distress syndrome, surfactant replacement therapy may also significantly reduce charges for ancillary services for these patients. In this way, surfactant therapy may be cost-effective by improving survival without increasing overall hospital costs. PMID- 2909957 TI - Mucocutaneous and invasive candidiasis among very low birth weight (less than 1,500 grams) infants in intensive care nurseries: a prospective study. AB - To determine whether mucocutaneous candidiasis presages the development of invasive candidiasis and to assess factors influencing the development of mucocutaneous candidiasis and invasive candidiasis among infants requiring neonatal intensive care, all infants admitted to our neonatal intensive care unit during a 47-month period were prospectively examined twice weekly for mucocutaneous candidiasis. Because 16 of 18 (89%) infants in whom invasive candidiasis (defined by positive cultures of blood, CSF, deep tissue or greater than or equal to 2 supra-pubic urine aspirates) developed had birth weights less than 1,500 g, further analysis was focused toward the very low birth weight group. Of 358 very low birth weight infants hospitalized for less than three days and serially studied until discharge from the neonatal intensive care unit, mucocutaneous candidiasis developed in 28 (7.8%), invasive candidiasis developed in 16 (4.5%), and in 323 there was no evidence of mucocutaneous candidiasis or invasive candidiasis. Although many risk factors were shown by univariate analysis to be significantly more common among those with invasive candidiasis and mucocutaneous candidiasis, adjustment for the covariant effects of duration of hospitalization and gestational age revealed that only prolonged duration of antibiotic therapy and duration of endotracheal intubation were significantly associated with invasive candidiasis. Invasive candidiasis developed later in nine of 28 (32%) infants with mucocutaneous candidiasis despite nystatin therapy of mucocutaneous candidiasis in all nine (median duration of therapy before invasive candidiasis, nine days). Very low birth weight infants in whom mucocutaneous candidiasis develops are at significantly greater risk of invasive candidiasis developing later than those in whom mucocutaneous candidiasis did not develop (9/28 v 7/330, P less than .001). PMID- 2909958 TI - Urine output measurement in premature infants. PMID- 2909959 TI - Miseducation: young children at risk. PMID- 2909960 TI - American Academy of Pediatrics Committee on Sports Medicine: Anabolic steroids and the adolescent athlete. PMID- 2909961 TI - American Academy of Pediatrics Committee on Drugs: SI units. PMID- 2909962 TI - American Academy of Pediatrics Committee on Adolescence: Adolescent pregnancy. PMID- 2909963 TI - American Academy of Pediatrics Committee on Adolescence: Counseling the adolescent about pregnancy options. PMID- 2909964 TI - American Academy of Pediatrics Committee on Adolescence: Care of adolescent parents and their children. PMID- 2909965 TI - American Academy of Pediatrics Committee on Nutrition: Indications for cholesterol testing in children. PMID- 2909966 TI - American Academy of Pediatrics Committee on Practice and Ambulatory Medicine: Office-based medication dispensing in pediatric practice. PMID- 2909967 TI - Haemophilus influenzae type b vaccine. PMID- 2909968 TI - Hair shampooing technique and pediatric vulvovaginitis. PMID- 2909969 TI - Theophylline, school performance, and the Food and Drug Administration. PMID- 2909970 TI - Discharge pack study. PMID- 2909971 TI - Adolescent medicine. PMID- 2909972 TI - Social competence and behavioral adjustment of children who are long-term survivors of cancer. AB - Relatively little is known about the special needs of long-term survivors of childhood cancer or the factors that make this growing population vulnerable to chronic psychologic disorders. We therefore surveyed 183 children who had been treated for cancer at St Jude Children's Research Hospital and were free of the disease for greater than or equal to 2 years after completing therapy. Parental responses to the Child Behavior Checklist, a standardized inventory of social competence and behavioral problems, were analyzed in relation to demographic and medical variables, as well as the children's appearance and functional status. School-related problems and somatic complaints of undetermined origin were increased fourfold relative to age- and gender-adjusted rates for peer groups in the general population. The presence of functional but not cosmetic impairments increased the risk of academic and adjustment problems. An older age at evaluation, treatment with cranial irradiation, and residence in a single-parent household were also associated with an increased risk of psychologic problems. General pediatricians must eventually assume responsibility for the extended follow-up care of children who have survived a malignancy. Their awareness of the high-risk groups described in this report should facilitate more timely identification of problems and referral of the children to appropriate services. PMID- 2909973 TI - Parental perceptions of health status and psychologic adjustment of children with asthma. AB - The relationship between severity of illness and psychologic adjustment was evaluated in 46 children with asthma. Two measures of the severity of asthma were used: the first, a composite objective measure based on clinical history and the second, parental estimates of the severity of their child's illness. Psychologic adjustment was measured by the Health Resources Inventory, a parental report of childhood behavior. Parental estimates of severity were correlated significantly with the objective measure of severity (r = .39; P less than .01), although a concordance value of 54% indicated marked lack of agreement between parental and objective ratings. As a group, children in this study achieved apparently normal adjustment scores, although scores ranged widely across all categories of severity. Children whose parents ranked their asthma as mild or severe had significantly lower adjustment scores (F = 3.28; P less than .05) than did those children rated by their parents as having moderate asthma. Children's ranks on the composite objective measure of severity were not associated with their adjustment scores, although children with greater use of medication had lower adjustment scores than did children with little or moderate medication use (P less than .05). The relationship of severity of illness to psychologic adjustment is complex. Children at all levels of severity may demonstrate problems of adjustment, suggesting that attention to psychologic risk should not be limited only to children with severe asthma. PMID- 2909974 TI - Infant-feeding practices and their relationship with diarrheal and other diseases in Huascar (Lima), Peru. AB - Longitudinal studies of the feeding practices and morbidity from infectious diseases of 153 Peruvian newborns from an underprivileged, periurban community were completed during their first year of life. Feeding practices were assessed by monthly questionnaires, and illnesses were identified by thrice-weekly, community-based surveillance. All infants were initially breast-fed, but only 12% were exclusively breast-fed at 1 month of age. At 12 months of age, 86% of children still received some breast milk. Incidence and prevalence rates of diarrhea in infants younger than 6 months of age were less among those who were exclusively breast-fed compared with those who received other liquids or artificial milks in addition to breast milk. The diarrheal prevalence rates doubled with the addition of these other fluids (15.2% v 7.1% of days ill, P less than .001). Infants for whom breast-feeding was discontinued during the first 6 months had 27.6% diarrheal prevalence. During the second 6 months of life, discontinuation of breast-feeding was also associated with an increased risk of diarrheal incidence and prevalence. Upper and lower respiratory tract infections occurred with lesser prevalence among exclusively breast-fed younger infants. The prevalences of skin infections by category of feeding practice were not as consistent, but exclusively breast-fed infants tended to have fewer skin infections during the initial months of life and older infants who continued to breast-feed had fewer infections than those who did not. None of the results could be explained by differences in the socioeconomic status of the infants' families. PMID- 2909975 TI - Child abuse by drowning. AB - Drowning as a form of subtle fatal child abuse is difficult to distinguish from accidental immersion or from sudden unexpected natural death when the circumstances of immersion are concealed. Homicidal drownings are unwitnessed, usually occurring in the home, and the victims are young, either infants or toddlers. Accidental drownings are more likely to involve toddlers or older children in public areas such as swimming pools, drainage ditches, lakes, and rivers. This is especially true in rural areas. In cities, bathtubs remain a major site of accidental childhood drownings. Perpetrators of deliberate drownings often fit the sociopathologic profile of a child abuser. Because there is often a survival interval between immersion and death, pathologic findings consistent with postimmersion syndrome suggest the cause of death. Foreign material in the lungs, if immersion was other than in clear tap water, and injuries of the face are other positive correlating factors. A thorough investigation of the circumstances and cooperation between the investigating agency and the pathologist are essential to determine the correct manner of death in these cases. PMID- 2909976 TI - Neonatal hyperparathyroidism: the natural course in the absence of surgical intervention. AB - The case of a premature infant with the onset of hypercalcemia and apparent primary hyperparathyroidism in the immediate neonatal period is presented. Although the treatment in most such cases has been parathyroidectomy, this infant was managed medically and survived infancy without apparent complications. We believe her disorder represents the neonatal manifestations of familial hypocalciuric hypercalcemia. Her course supports the contention that this disorder may be self-limited in some infants and that appropriate medical management can preclude the need for surgical intervention in selected cases. PMID- 2909977 TI - Dietary replacement in preschool-aged hyperactive boys. AB - A 10-week study was conducted in which all food was provided for the families of 24 hyperactive preschool-aged boys whose parents reported the existence of sleep problems or physical signs and symptoms. A within-subject crossover design was used, and the study was divided into three periods: a baseline period of 3 weeks, a placebo-control period of 3 weeks, and an experimental diet period of 4 weeks. The experimental diet was broader than those studied previously in that it eliminated not only artificial colors and flavors but also chocolate, monosodium glutamate, preservatives, caffeine, and any substance that families reported might affect their specific child. The diet was also low in simple sugars, and it was dairy free if the family reported a history of possible problems with cow's milk. According to the parental report, more than half of the subjects exhibited a reliable improvement in behavior and negligible placebo effects. In addition, several nonbehavioral variables tended to improve while the children received the experimental diet, particularly halitosis, night awakenings, and latency to sleep onset. PMID- 2909978 TI - Morbidity for survivors of extracorporeal membrane oxygenation: neurodevelopmental outcome at 1 year of age. AB - Extracorporeal membrane oxygenation is an important technology in the treatment of high-risk infants whose long-term outcome is being followed prospectively at our institution. The extracorporeal membrane oxygenation procedure allows temporary cardiopulmonary support for critically ill full-term neonates who are refractory to maximum ventilatory and medical management as a consequence of severe persistent pulmonary hypertension. The technique necessitates both the permanent ligation of the right common carotid artery and jugular vein and systemic heparinization. The survivors constitute a unique group of high-risk infants, from the standpoint of the hypoxic-ischemic insults preceding extracorporeal membrane oxygenation and the risks associated with the procedure. Our results indicate that most of our survivors are developing normally at 1 year. Major morbidity, in terms of either significant developmental delay (Bayley mental and motor indices less than 70) or significant neuromotor abnormality, occurred in only 10% of these infants. Poor outcome was associated with major intracranial hemorrhage and chronic lung disease. Ligation of the right carotid artery and jugular vein was not associated with a consistent lateralizing lesion. Long-term follow-up through school age is essential. PMID- 2909979 TI - Ureaplasmal pneumonia and sepsis associated with persistent pulmonary hypertension of the newborn. AB - Ureaplasma urealyticum was isolated from the lower respiratory tract of three infants with persistent pulmonary hypertension of the newborn. In one, cultures positive for U urealyticum were obtained on multiple occasions from trachea, blood, and pleural fluid prior to the infant's death on postnatal day 6. Autopsy findings confirmed the presence of severe pneumonia and the organism was again recovered from multiple sites. A second infant had no apparent predisposing factors for development of persistent pulmonary hypertension of the newborn but U urealyticum and Staphylococcus epidermidis were recovered from the trachea antemortem and from lung tissue obtained during autopsy on the 12th postnatal day. The third infant had persistent pulmonary hypertension of the newborn and a pulmonary infiltrate within hours after birth with tracheal cultures positive for both U urealyticum and Mycoplasma hominis. Erythromycin was given for ten days, and the infant gradually improved. Prolonged ventilation with supplemental oxygen was necessary, and chronic lung disease developed. This is the first report of neonatal ureaplasmal pneumonia with sepsis and persistent pulmonary hypertension of the newborn as well as the first time a microorganism other than streptococci has been specifically implicated in the pathogenesis of persistent pulmonary hypertension of the newborn. Respiratory infections with U urealyticum or other bacteria should be considered as possible causative or contributory factors in infants with persistent pulmonary hypertension of the newborn. PMID- 2909980 TI - Feeding and urine cotinine values in babies whose mothers smoke. AB - In Canada, 8% to 20% of infants are breast-fed by mothers who smoke. To determine whether breast-feeding increases infants' exposure to tobacco smoke products, urinary cotinine excretion was measured in 172 babies, 33 of whom were breast fed. A milk sample was taken from the mothers who were breast-feeding, and cotinine was measured with gas chromatography. The breast-fed babies had a median cotinine to creatinine ratio of 433 ng/mg, whereas the bottle-fed babies' median was 200 ng/mg (P less than 10(-4)). Similar differences were observed after adjustment for the number of cigarettes smoked by the mother and by other smokers in the home in the previous 24 hours. The correlation coefficient between the number of cigarettes smoked by the mother and the breast milk cotinine concentration was significant (r = .69, P = 2 X 10(-4)). Moreover, urine cotinine values from the breast-fed babies increased with higher concentrations of cotinine in the mother's milk (r = .56, P = .02). These results provide evidence that breast-feeding increases exposure to tobacco smoke components in infants whose mothers smoke. This is yet another argument for strongly encouraging women who smoke to stop smoking during pregnancy and lactation. PMID- 2909981 TI - Preductal and postductal transcutaneous oxygen tension measurements in premature newborns with hyaline membrane disease. AB - Pre- and postductal transcutaneous oxygen tension (tcPO2) was measured in 23 preterm infants with hyaline membrane disease to estimate the degree of right to left ductal shunting. The study was done during the first 24 hours of life and the data were recorded continuously. The studies were 11.9 +/- 4.0- hours long, (mean +/- SD) and the difference between the pre- and postductal tcPO2 (delta TcPO2) was measured every 100 seconds. Of 9,872 determinations, the delta tcPO2 was less than or equal to 15 mm Hg in 90.1%, 16 to 29 mm Hg in 9.3%, and greater than or equal to 30 mm Hg in 0.6%. It was concluded that large differences between pre- and postductal oxygen tension are rare in infants with hyaline membrane disease. The results of this and other published data suggest that it is unlikely that measurement of PaO2 in the descending aorta or tcPO2 below the ductus places infants at an increased risk of having retinopathy of prematurity develop. PMID- 2909982 TI - Back to the bases. PMID- 2909983 TI - Memory in a neuron. PMID- 2909984 TI - Schizophrenic results. PMID- 2909985 TI - Modification of protein synthesis initiation factors and the shut-off of host protein synthesis in adenovirus-infected cells. AB - A substantial body of data, largely derived from study of cell extracts, indicates that protein synthesis in adenovirus-infected cells requires VA RNAI at late times of infection to prevent the activation of a protein kinase known as DAI, and the consequent phosphorylation of the alpha-subunit of initiation factor eIF-2. To verify this conclusion, we have measured the steady-state levels of eIF 2 alpha phosphorylation in cells infected with wild-type virus (Ad2) and a mutant that produces no VA RNAI (Ad5dl331). Consistent with the proposed mechanism, the alpha-subunit was very highly phosphorylated (approximately 90%) at late times of infection with Ad5dl331. Surprisingly, eIF-2 alpha phosphorylation also increased (to approximately 30%) at late times of infection with Ad2, suggesting that VA RNA and DAI might be involved in the selective translation of viral mRNA and the shut-off of host cell protein synthesis during the late phase. In agreement with this model, host protein synthesis shut-off is defective in cells expressing low levels of DAI. PMID- 2909986 TI - Characterization of novel populations of MVM virions containing covalent DNA protein complexes. AB - Virions of minute virus of mice were purified by sedimentation in sucrose gradients and chromatography on DEAE-cellulose columns and shown to consist of single-stranded viral DNA and the viral capsid polypeptides VP-1 (83 kDa) and VP 2 (64.5 kDa). A 63-kDa polypeptide distinct from the viral capsid polypeptide VP 3 (61.4 kDa) was found in some virion preparations. Virions sedimented at 135 and 110 S. The genomic single strands associated with purified 135 and 110 S virions were covalently bound to a protein as judged by the anomalous electrophoretic mobility of the DNA in agarose gels at pH 12.5. The protein was removed from the DNA by Pronase but remained bound after heating at 98 degrees in the presence of 0.1% sodium dodecyl sulfate. Nuclease digestion of the purified DNA-protein complex released several polypeptides ranging in size from 58 to 65 kDa. Restriction enzyme analysis of the purified DNA protein complex following its conversion to a duplex RF DNA in vitro showed that the protein was attached to the 5' termini of the DNA. PMID- 2909987 TI - Virus-ribosome complexes from cell-free translation systems supplemented with cowpea chlorotic mottle virus particles. AB - When particles of cowpea chlorotic mottle virus (CCMV) were added to cell-free extracts from wheat germ, the encapsidated viral genome was translated into polypeptides similar to the translation products specified by unencapsidated viral RNA (as shown before by M.J. Brisco, R. Hull, and T.M.A. Wilson, 1986, Virology 148, 210-217). The rate of protein synthesis observed upon addition of virus particles was much slower than that of extracted RNA and the quantity of protein formed was only 10% of that of extracted RNA. Using sucrose and cesium chloride gradient analysis, virus-ribosome complexes, containing up to four ribosomes per virus particle, were isolated from translation mixtures supplemented with CCMV particles. These complexes, with densities intermediate of those of virus (1.36 g cm-3) and ribosomes (1.58 g cm-3), were analyzed and quantified in the electron microscope. Less than 5% of the particles was found in association with ribosomes. To verify whether these complexes were involved in the process of cotranslational disassembly, tobacco mosaic virus was analyzed with the same techniques and methods. The results found for TMV were similar to those found for CCMV except that virus-ribosome complexes with up to 20 ribosomes per virus particle were observed. The implications of the process of virion directed translation for the structure of the particle as well as the role of this process in vivo are discussed. PMID- 2909989 TI - The use of sulfite to study the mechanism of membrane fusion induced by E1 of Semliki Forest virus. AB - In this study we have used 35S-labeled sulfite to modify the disulfide bonds of the proteins at the cell surface of Semliki Forest-infected Aedes albopictus cells before and after low pH treatment. This reagent specifically cleaves disulfide bonds and concomitantly reacts with the newly formed cysteines, thereby labeling the respective protein. Treatment of the infected cells with sulfite led to inhibition of the fusion activity only when applied after low pH exposure. These cells exhibited substantial incorporation of the label into the viral E1 glycoprotein as compared to the E2 glycoprotein. These results provide direct evidence for the low pH-induced conformational change of E1 during the generation of its fusogenic potential. PMID- 2909988 TI - Studies on the mechanism of the antiviral activity of ribavirin against reovirus. AB - We have examined the mechanism by which ribavirin inhibits the multiplication of reovirus. At a concentration of 12.5 microM (3 micrograms/ml) ribavirin inhibits viral multiplication, ssRNA formation, dsRNA formation, and protein synthesis by about 90%; when much higher concentrations are used for brief periods of time, the primary target of ribavirin is seen to be viral ssRNA synthesis. When the effect of ribavirin triphosphate (RTP) was tested on the in vitro transcription by cores of the dsRNA genome segments into plus-stranded RNA, elongation, that is, the formation of intact mRNA molecules, was found to be inhibited to the greatest extent; initiation was at least 2.5 times less sensitive, and cap formation and methylation were almost unaffected. The inhibition of elongation and initiation was not competitive with respect to any of the four nucleoside triphosphates. Remarkably, the transcription of plus strands into minus strands by immature reovirus particles (the replicase reaction) was insensitive to RTP. A model is proposed that envisages RTP binding to a site close to the catalytic site of the transcriptase. This binding is postulated to inhibit the helicase function of the transcriptase and lower its affinity for template RNA so that the likelihood of premature termination is greatly increased. The helicase activity is not, of course, necessary for the transcription of plus strands into minus strands, which would account for the differential sensitivity of the transcriptase and the replicase to RTP. PMID- 2909990 TI - Identification of the 5' end of the rubella virus subgenomic RNA. AB - The 5' end of the subgenomic RNA of rubella virus was determined by primer extension. The Maxam-Gilbert sequence ladder of the primer extension product contained a determinable sequence which was colinear with the complement of the sequence of the genomic RNA through nucleotide 3325 from the 3' end of the genomic RNA and a pair of bands in every lane above the determinable sequence. These results indicated that synthesis of the subgenomic RNA is initiated internally on the minus-polarity genome-length RNA template and that the length of subgenomic RNA is 3327 nucleotides excluding the poly(A) tail. There are thus 77 nucleotides between the 5' end of the subgenomic RNA and the first AUG, which is the initiation codon for the structural protein open reading frame. The initiation site of rubella virus subgenomic RNA synthesis is 20 nucleotides downstream from a block of 28 nucleotides which shares homology with the nucleotide sequence which is conserved at the subgenomic RNA initiation site in the Alphaviruses, the other genus of Togaviruses. PMID- 2909992 TI - A symposium: The role of phosphodiesterase III inhibitors in contemporary cardiovascular medicine. April 9, 1988, New York, New York. PMID- 2909991 TI - Assignment of wound tumor virus nonstructural polypeptides to cognate dsRNA genome segments by in vitro expression of tailored full-length cDNA clones. AB - Presumptive full-length cDNA clones of 9 of the 12 wound tumor virus double stranded RNA genome segments were tailored for efficient in vitro expression by a recently described strategy [Z. Xu, J.V. Anzola, and D.L. Nuss (1987) DNA6, 505 513]. In vitro synthesized polypeptides specified by synthetic transcripts corresponding to the tailored cDNAs comigrated in polyacrylamide gels with in vivo synthesized viral-specific polypeptides. This analysis confirmed the functional integrity of the tailored cDNA clones and identified cognate genome segments which encode all five viral non-structural polypeptides as well as four structural polypeptides; two which comprise the capsid, one located in the viral core and one associated with the outer protein coat. PMID- 2909993 TI - Observations on the intracoronary administration of milrinone and dobutamine to patients with congestive heart failure. AB - A direct intracoronary infusion technique was used to characterize the mechanisms of action of milrinone, a new phosphodiesterase inhibitor. Because of the small quantity of drug infused, it is possible to achieve a therapeutic concentration of drug in the heart with little or no systemic accumulation. Because loading conditions are largely unaffected during intracoronary drug infusion, it is possible to use left ventricular +dP/dt as a convenient measure of changes in contractility. Intracoronary milrinone infusion caused a dose-related increase in +dP/dt associated with a substantial improvement in left ventricular pump function. In addition, there is a small decrease in heart rate, which appeared to be secondary to reflex withdrawal of sympathetic tone, since it was associated with a decrease in plasma norepinephrine. Measurement of forearm vascular resistance and forearm venous capacitance by plethysmography indicated that although there was no significant decrease in forearm vascular resistance during intracoronary drug infusion, there was a small increase in venous capacitance. Subsequent intravenous administration of milrinone caused a substantial further improvement in left ventricular pump function, associated with a substantial decrease in left- and right-sided cardiac filling pressures and forearm vascular resistance, and an increase in forearm venous capacitance. These findings suggest that reflex sympathetic withdrawal may contribute to the venous dilation that occurs with milrinone, but that the major effects of milrinone on vascular tone are due to a direct vascular action of the drug. Intracoronary infusion of dobutamine has also demonstrated a substantial decrease in the inotropic response to beta-adrenergic stimulation in patients with congestive heart failure, presumably because of down-regulation of beta-adrenergic receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2909994 TI - Effects of phosphodiesterase inhibition on skeletal muscle vasculature. AB - The pathophysiology of the syndrome of congestive heart failure (CHF) includes 2 major components that closely interact. The first one is a reduction in ventricular performance, which is manifested initially during exercise and is later present at rest. The second one involves abnormalities of the peripheral circulation and organs, which become gradually more prominent and lead ultimately to symptoms. The exercise capacity of patients with chronic CHF is limited not only by an inadequate increase in cardiac output and an excessive increase in ventricular filling pressure, but also by a fixed vasodilatory response to exercise. Although the role of increased activity of the sympathetic and renin angiotensin-aldosterone systems in the derangements of the peripheral circulation has been extensively investigated, the structural abnormalities of the arterial wall have received little emphasis in patients with CHF. Chronic reduction of the cardiac output may lead to endothelium-dependent reduction in arterial diameter and vasomotor response, which may in turn increase systemic vascular resistance and further reduce cardiac output. Therapeutic agents should be characterized by their acute and chronic effects not only on ventricular performance, but also on the peripheral circulation. More specifically, when one is concerned with the effect of a therapeutic intervention on exercise capacity, evaluation of its direct and indirect effects on the skeletal muscle vasculature is particularly important. Accordingly, the effects of phosphodiesterase inhibition on vascular smooth muscle tone and skeletal muscle vasculature are reviewed. In addition, the potential of phosphodiesterase inhibition to reverse structural abnormalities of the arterial wall is discussed. PMID- 2909995 TI - Electrophysiology of phosphodiesterase inhibitors. AB - Phosphodiesterase inhibitors appear to uniformly enhance atrioventricular node conduction, although milrinone seems to have the least effect. Except for digoxin, this effect on atrioventricular node conduction is similar to that noted with other inotropic agents. Other electrophysiologic effects vary among patients, with enoximone being more theophylline-like in response. Because none of these drugs do not have an adverse effect on His-Purkinje conduction, they are safe to use in patients with intraventricular conduction disturbances. Significant proarrhythmia is uncommon, but can occur. The mechanisms causing these electrophysiologic changes are not well defined, but the changes may occur because of increased concentrations of cytosol cyclic adenosine monophosphate secondary to phosphodiesterase inhibition, increased cytosol calcium levels secondary to increased cyclic adenosine monophosphate, or reflex adrenergic stimulation secondary to the peripheral vasodilating effects of these drugs. PMID- 2909996 TI - Effect of intravenous metoprolol on left ventricular performance in Q-wave acute myocardial infarction. AB - To determine the effects of intravenous metoprolol on left ventricular (LV) function in acute myocardial infarction (AMI), 16 patients were studied within 48 hours of Q-wave AMI (mean ejection fraction 47 +/- 6%, mean pulmonary artery wedge pressure 22 +/- 6 mm Hg) with high fidelity pressure and biplane cineventriculography before and after intravenous metoprolol (dose 12 +/- 4 mg). Heart rate decreased from 90 +/- 13 to 74 +/- 11 beats/min (p less than 0.001), pulmonary arterial wedge pressure and LV end-diastolic pressure were unchanged (22 +/- 6 to 21 +/- 6 and 27 +/- 8 to 26 +/- 8 mm Hg, respectively), despite impaired LV relaxation (P = Poe-t/T) after intravenous metoprolol (T from 59 +/- 13 to 72 +/- 12 ms, p less than 0.001). Peak systolic circumferential LV wall stress decreased after beta-adrenergic blockade (330 +/- 93 to 268 +/- 89 g/cm2, p less than 0.05) and LV contractility decreased (dP/dtmax from 1,480 +/- 450 to 1,061 +/- 340 mm Hg/s, p less than 0.001). The ejection fraction decreased (48 +/ 7 to 43 +/- 7%, p less than 0.05) due to an increase in LV end-systolic volume (85 +/- 19 to 93 +/- 19 ml, p less than 0.05) since LV end-diastolic volume was unchanged (161 +/- 30 to 163 +/- 30 ml, difference not significant). In patients with Q-wave AMI, intravenous metoprolol reduces the major determinants of myocardial oxygen demand including heart rate, contractility and peak systolic wall stress. Further, despite decreased heart rate, (+)dP/dtmax, ejection fraction, isovolumic relaxation, LV end-diastolic pressure and end-diastolic volume remain unchanged. PMID- 2909997 TI - External cardiac programmed stimulation for noninvasive termination of sustained supraventricular and ventricular tachycardia. AB - To examine the feasibility of using a noninvasive temporary pacemaker for termination of well-tolerated supraventricular (SVT) and ventricular tachycardia (VT), a standard external demand pacemaker was modified to allow stimulation with single or multiple extrastimuli and overdrive pacing. To evaluate the efficacy, safety and tolerance of external cardiac programmed stimulation, a standard arrhythmia termination protocol was used in 223 tachycardias in 22 patients. The technique of external cardiac programmed stimulation was used in 209 episodes of SVT in 13 patients. It terminated 95% of the episodes with success in 19 of 20 episodes of atrioventricular nodal reentrant tachycardia and 179 of 189 episodes of atrioventricular reciprocating tachycardia. Of 198 episodes of SVT terminated by the technique 168 (85%) were terminated by a single extrastimulus and 28 (14%) by double extrastimuli. Only 2 episodes of SVT required overdrive pacing for termination. External cardiac programmed stimulation did not result in atrial fibrillation or arrhythmia acceleration. Of 14 episodes of sustained monomorphic VT 5 were terminated by external cardiac programmed stimulation. One tachycardia was terminated by a single extrastimulus, 1 by double extrastimuli and 3 by overdrive pacing. Arrhythmia acceleration occurred once and was terminated by endocardial pacing. On 27 separate occasions patient evaluation of maximal discomfort included 4 ratings of mild, 10 of moderate, 11 of severe and 2 of intolerable discomfort. External cardiac programmed stimulation is effective and safe in patients with well-tolerated sustained supraventricular or ventricular arrhythmias. PMID- 2909998 TI - Usefulness of isoproterenol during atrial fibrillation in evaluation of asymptomatic Wolff-Parkinson-White pattern. AB - The asymptomatic individual with a Wolff-Parkinson-White (WPW) pattern is considered at risk for ventricular fibrillation if a rapid ventricular response (shortest RR interval less than or equal to 250 ms) is observed during induced atrial fibrillation (AF) in the laboratory. It has been suggested that isoproterenol administration during AF may more accurately define the patient at risk. Consequently, the effect of isoproterenol on ventricular response during AF was studied in 21 asymptomatic individuals with WPW pattern to assess the potential of isoproterenol to identify patients at risk for sudden death. An electrophysiologic study that included elective induction of AF was performed. The shortest and mean RR intervals between 2 consecutive preexcited and normal QRS complexes, the average RR interval and the proportion of preexcited QRS complexes were measured in the control state and after bolus injections of isoproterenol (0.5, 1.0, 2.0 and 4.0 micrograms) during AF. Both atrioventricular nodal and accessory pathway conductions were enhanced proportional to isoproterenol dose. Isoproterenol had a greater effect on the atrioventricular node, as reflected by significantly greater changes in the shortest RR between normal complexes (339 +/- 70 vs 255 +/- 21 ms, mean +/- standard deviation, p less than 0.001) than the shortest RR between preexcited complexes (264 +/- 39 vs 219 +/- 34 ms, p less than 0.001) and a decrease in percentage of preexcited complexes (65 +/- 37 vs 50 +/- 33%, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2909999 TI - Echocardiographic and clinical predictors for outcome of elective cardioversion of atrial fibrillation. AB - Previous studies have suggested that success of elective direct-current cardioversion for atrial fibrillation (AF) can be predicted from clinical features and M-mode echocardiographic left atrial diameter. We evaluated clinical variables as well as M-mode and 2-dimensional echocardiographic measurements of atrial size in 85 patients undergoing electrical cardioversion for AF. Of 65 patients who were initially converted to sinus rhythm, 45 (69%) and 38 (58%) remained in sinus rhythm at 1 and 6 months, respectively. No historical feature predicted initial success, although patients with cardiomyopathy or pulmonary disease underlying their AF had significantly lower success rates compared with those having other etiologies. Furthermore, no M-mode or 2-dimensional echocardiographic measurements of atrial size predicted initial success of cardioversion. Maintenance of sinus rhythm at 1 month was related to short duration of AF before cardioversion (less than 3 months vs greater than 12 months, p less than 0.05). Left atrial area and long axis dimension by 2 dimensional echocardiography were significantly larger in patients remaining in sinus rhythm than in those who had reverted to AF at 1 month (28 +/- 7 vs 24 +/- 5 cm2 and 65 +/- 9 vs 59 +/- 8 mm, respectively, both p less than 0.05), but overlap was great. No significant difference in atrial dimensions was noted at 6 month follow-up. It appears that, although no clinical or echocardiographic variable predicts initial success for cardioversion of AF, duration of AF does predict maintenance of sinus rhythm 1 month after initial success.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2910000 TI - Response in oxygen uptake and ventilation during stair climbing in patients with chronic heart failure. AB - To examine the level of muscular work and ventilatory response to stair climbing (mobile Stairmaster staircase, 1 step/2.5 s), respiratory gas exchange, ventilation, heart rate and arterial pressure were monitored in patients with chronic heart failure and their response compared with that of normal individuals. Aerobic capacity (maximal oxygen uptake) and anaerobic threshold during treadmill exercise were also determined and used to ascertain the metabolic cost of stair climbing. No differences were observed in the response of mean arterial blood pressure between the 12 patients and 10 normal subjects during exercise or recovery. However, the heart rate and oxygen consumption obtained during exercise were significantly lower in the patients with chronic heart failure than in the normal subjects (p less than 0.05). All patients with a maximal oxygen uptake less than 20 ml/min/kg during treadmill exercise had an oxygen uptake during stair climbing that exceeded their anaerobic threshold and, consequently, they attained a significantly (p less than 0.01) higher level of ventilation during exercise and recovery. This was not the case for those patients with greater aerobic capacity. Therefore, it is concluded that stair climbing for the 12 patients with heart failure and moderate to moderately severe impairment in aerobic capacity represents strenuous anaerobic exercise. The resultant excess ventilation may explain the limiting sensation of dyspnea that is frequently experienced by these patients during and after stair climbing. PMID- 2910001 TI - Right ventricular myocardial function after atrial switch operation for transposition of the great arteries. AB - Postoperative right ventricular (RV) myocardial function was evaluated in 6 patients who underwent atrial switching for simple transposition of the great arteries (TGA). The average age at study was 5.5 years. RV function was evaluated at rest and during administration of methoxamine by cardiac catheterization and RV angiography. The data were compared with left ventricular function in a control group, which consisted of 6 patients, 3 with functional murmur and 3 with pulmonary valvar stenosis. During stress, the TGA group showed a significant increase in end-diastolic pressure, minute work index and end-diastolic and end systolic volume indexes, along with a significant decrease in ejection fraction. The control group also showed an increase in these variables except for ejection fraction during stress, which did not change. The slope of the work-function curve for the TGA group was lower than that for the control group (p = 0.02). The TGA group had a lower slope of the peak systolic pressure-volume relation than the control group (p = 0.005). There was no significant correlation between the slope of the peak systolic pressure-volume relation and age at repair or study. This study shows that RV pump dysfunction observed in postoperative TGA patients may be caused by depressed myocardial function. PMID- 2910002 TI - Differences in effects of aerobic exercise training on blood lipids in men and women. PMID- 2910003 TI - Relation of left ventricular ejectional flow velocity to volume ejection rate. PMID- 2910004 TI - Optimal Doppler measurement of left ventricular ejection time. PMID- 2910005 TI - Effect of repeated reperfusion on the size of experimental myocardial infarction. PMID- 2910006 TI - Holter monitoring versus treadmill exercise test in the detection of myocardial ischemia. PMID- 2910007 TI - Alcohol use and supraventricular arrhythmia. PMID- 2910008 TI - Nomenclature for the use of balloon catheters. PMID- 2910009 TI - Parental transmission of congenital heart disease. PMID- 2910010 TI - Fatal acute spontaneous endometritis resulting from Clostridium sordelli. AB - Intrauterine clostridial infections have historically been associated with puerperal sepsis, often subsequent to instrumented abortions. Isolated reports have been associated with a malignant neoplasm or degenerating leiomyoma, most often after instrumentation, radiation therapy, or chemotherapy. In these cases, well-known risk factors or obvious niduses for growth and causation of disease were identified. The authors report a case of fatal spontaneous endometritis resulting from Clostridum sordellii, which, to their knowledge, has not been previously reported in the literature. Characteristics of this rare virulent human pathogen are discussed. PMID- 2910011 TI - Necessary comment. PMID- 2910012 TI - Dual parameter analysis of myeloma cells by flow cytometry. DNA content of cells containing monotypic cytoplasmic immunoglobulin. AB - Dual-parameter flow cytometric analysis of monotypic cytoplasmic immunoglobulin (CIg) and DNA content on 15 myeloma marrows allowed S-phase determination of the CIg(+) tumor separately from the CIg(-) hematopoietic cell pool. The median percentage of the CIg(+) cells in S-phase was 2% compared with 5% for the CIg(-) cells. The median survival of patients with more than 2%, and those with 2% or less CIg(+) S-phase cells was 2 months and more than 13 months, respectively, from the time of study. Ploidy analysis identified four patterns of plasma cell DNA content: entirely hyperdiploid, entirely diploid, combined diploid and tetraploid stemlines, and tumors containing diploid and aneuploid CIg(+) cells. A monotypic CIg(+) double stemline myeloma was distinguished from two aneuploid tumors containing admixed normal, diploid polyclonal plasma cells. This technique provides an improved and expedient means for determining the proliferating fractions of myeloma cells and enhances recognition of double stemline tumors and clonal evolution in myeloma. PMID- 2910013 TI - Frequency of occurrence of diagnostic cytologic parameters in basal cell carcinoma. A retrospective review of 25 cases. AB - Twenty-five cases of cytologic preparations from basal cell carcinomas documented by subsequent tissue material were obtained. The cases were retrospectively analyzed to evaluate the frequency of occurrence of various features that could either be helpful or misleading in the diagnosis. These features included peripheral palisading, Bowenoid nuclei, and keratinized cells. Results from the study include the fact that a major criterion for the histologic diagnosis of basal cell carcinoma (peripheral palisading) could seldom be appreciated in the cytology preparations. Large clusters of cells with crowded nuclei were found in every case and thus represent a useful cytologic parameter. However, because of the frequent absence of peripheral palisading, the study suggests there could be diagnostic confusion with lesions of small cell squamous carcinoma. PMID- 2910014 TI - A comparative study of variables affecting the bleeding time using two disposable devices. AB - A number of variables affect the result of the bleeding time, the most frequently used test assessing primary hemostasis. Although the test is now usually performed with one of several commercially available disposable devices, most previous studies of the bleeding time have evaluated only the original template device described nearly 20 years ago. Therefore, we compared two commonly used bleeding time devices (Surgicutt and Simplate) with regard to multiple variables affecting the test in 40 hematologically normal young adults. Bleeding time was performed by the modified Ivy method according to the manufacturers' instructions in both horizontal (transverse) and vertical directions, before and two hours after a test dose of 650 mg of aspirin was administered. With both horizontal and vertical incisions, Simplate bleeding time values were greater than with the Surgicutt device (P = 0.0025). Bleeding time in the horizontal direction was greater than vertical with both devices (P = 0.0001). Values in males and females were not significantly different. Aspirin sensitivity, the difference between preaspirin and postaspirin values, was greatest with the use of the Surgicutt device in the horizontal position (mean postaspirin value 8.0 minutes). Both devices produced a reproducible uniform incision, caused minimal discomfort, and resulted in little or no scarring. The authors conclude that the results with Surgicutt and Simplate devices were comparable in many respects but that a horizontal Surgicutt bleeding time might be most sensitive in detecting disorders of primary hemostasis. Comparative studies of different bleeding time devices in normal subjects are necessary in order to accurately assess their clinical utility. PMID- 2910015 TI - Myelodysplasia with bone marrow lymphocytosis and fibrosis mimicking recurrent Hodgkin's disease. AB - Myelodysplastic syndromes and acute leukemias after treatment for Hodgkin's disease (HD) are well recognized. Preleukemic changes are commonly seen. Three patients from the authors' files are found with myelofibrosis and bone marrow lymphocytosis after treatment for HD. Although somewhat unusual, the clinical impression initially was, in each case, isolated recurrence of HD involving the bone marrow, 6 to 11 years after initial diagnosis. In each case, after single or multiple marrow aspirates and biopsies were done, the differential between HD involving the marrow and myelodysplasia with myelofibrosis and lymphocytic infiltrates was made. The absence of diagnostic Reed-Sternberg (RS) cells was useful in diagnosing the latter. All three patients died of causes related to cytopenias, with two having progressed to overt acute nonlymphocytic leukemia. Myelofibrosis with lymphocytic infiltrates in the marrow, without diagnostic RS cells, in patients' status after treatment for HD, should alert one to the possibility of myelodysplasia. PMID- 2910016 TI - Nucleoli of blood monocytes in malignant lymphoma. A morphometric study. AB - Morphometric methods were used to study the nucleolar ultrastructure of blood monocytes in 23 patients with Hodgkin's disease, 12 patients with non-Hodgkin's lymphoma, and 20 normal subjects. Nucleolar volume (Vn), surface area (Sn), volume fraction within the nucleus (VVn), surface-to-volume ratio, and number of nucleolar profiles per section were measured. The results were examined with the use of multivariate and univariate analyses of variance, and significant differences between the patient and normal groups were found. Compared with the normals, values for Vn, Sn, VVn and number of profiles per section were 16-20% smaller in the Hodgkin's monocytes and 19-32% smaller in those of the patients with non-Hodgkin's lymphoma. The changes in nucleolar ultrastructure may be related to the known mononuclear phagocyte dysfunction in patients with lymphoma. PMID- 2910017 TI - Reproducibility in quality control of protein (Western) immunoblot assay for antibodies to human immunodeficiency virus. AB - The protein (Western) immunoblot assay (IB) for antibodies to human immunodeficiency virus, like other laboratory procedures, sometimes gives variable results. In the Transfusion Safety Study, indistinguishable aliquots of four quality control (QC) samples have been routinely submitted for IB with each group of patient specimens. A false negative IB result was obtained for 1.7% of 179 assays of two known positive (QC) standards and a false positive result for 2.0% of 101 assays of two known negative (QC) standards. In addition, a test panel of 24 samples was sent on a single occasion to three widely used laboratories. A false positive result was reported by one laboratory and a false negative by a second. Although generally reliable, IB results may occasionally be in error. There is much more technical variability in the relative frequencies of antigen-antibody bands than has been recognized. These interlaboratory and intralaboratory comparisons show quality control checks are essential for all laboratories, and more than one specimen should be tested if its applicability to a specific patient is questionable. Specific bands are sufficiently inconstant for the same specimen to make appearance or disappearance on successive specimens prognostically unreliable. PMID- 2910018 TI - Does determination of serum aspartate aminotransferase contribute to the diagnosis of acute myocardial infarction? AB - Values for total lactate dehydrogenase (LD), LD isoenzymes, and serum aspartate aminotransferase (AST) were determined in 150 patients with acute myocardial infarction (AMI) and 130 non-AMI patients 24, 48, and 72 hours after admission. The authors assessed the diagnostic yield of a single determination of AST, LD, and three LD isoenzymes tests: LD-1 greater than LD-2; LD-1 greater than 90 U/L; LD-1/LD greater than 0.4. They also assessed the diagnostic accuracy of combined determination of AST with LD and AST with each of the above three LD isoenzymes tests. The efficiency of single determination of AST was better than that of LD (88% vs. 80%, 48 hours after admission). The most efficient single test for diagnosing AMI was the LD-1 greater than 90 U/L test (92%, 48 hours after admission). The efficiency of the combined AST/LD test was better than that of a single determination of each of the two enzymes (90% vs. 88% and 80%, 48 hours after admission). The highest efficiency was achieved, however, with combined determination of AST and any of the three LD isoenzymes tests. It was found to be more efficient than single determination of each of the LD isoenzymes tests (95.5 96% vs. 89-92.5%) and more efficient than the combined determination of the AST/LD test (95.5-96% vs. 89-90%). The authors conclude that AST should be determined in every patient with suspected AMI because its determination may contribute to the diagnostic yield of LD isoenzymes tests, especially in patients with AMI admitted 48-72 hours after onset of symptoms, when creatine kinase declined to near normal values. PMID- 2910019 TI - Spirochetes in the spleen of a patient with chronic Lyme disease. AB - A 54-year-old man had intermittent evening fever, arthralgia, transient erythematous macular eruption on the skin, and splenomegaly of two year's duration. Immunofluorescence tests for Borrelia burgdorferi serum antibodies had positive results, but G-penicillin treatment was ineffective. Splenectomy with lymph node biopsy was performed to rule out lymphoproliferative disorders. Borrelia-like spirochetes were identified histologically in the spleen; this finding was consistent with persistence of B. burgdorferi organisms in inner organs in chronic Lyme disease. PMID- 2910020 TI - Hepatic granuloma resulting from Enterobius vermicularis. AB - A nodule of the liver was incidentally noted during left colectomy for a large villous adenoma in a 74-year-old man. Microscopic examination disclosed a granuloma of the liver containing numerous Enterobius vermicularis ova and a cross-section of the nematode. This is the fourth reported case of hepatic oxyuriasis and the second case reported in North America. PMID- 2910021 TI - An American Board of Orthodontics case report. A combined face mask-orthognathic surgical approach in the treatment of skeletal open bite and maxillary deficiency. AB - This case report is presented following the specifications of the American Board of Orthodontics. The patient had a true skeletal open bite with maxillary and mandibular asymmetry. She was treated with an orthognathic surgical approach and face mask therapy to stabilize the postsurgical result. PMID- 2910022 TI - Mandibular displacement and dentitional changes during orthodontic treatment and growth. AB - Mandibular displacement during orthodontic treatment and/or growth is usually analyzed through cephalometric superposition on the cranial base. Evaluation of mandibular movement in relation to the maxillary base has considerable value because the occlusion of the teeth is associated directly with the position of the maxillary and mandibular basal bones. The method of superimposition is outlined and applied to a number of treated malocclusions. Incorporation of this method in the study of treatment results is suggested. PMID- 2910023 TI - Cause of early skeletal relapse after mandibular setback. AB - The present study was undertaken to examine the factors that might be responsible for the skeletal relapse occurring during the period of intermaxillary fixation after mandibular setback osteotomy. Fifteen patients, treated for absolute mandibular prognathism by modified sagittal split ramus osteotomy and fixation by skeletal suspension wiring, were evaluated cephalometrically by reference to the degree of postsurgical superior shift of the gonial region of the distal segment as a parameter of relapse since such a shift was evident despite the use of wiring. It was found that the degree of inadvertent anteroposterior rotation of the proximal segment at surgery, rather than the extent and pattern of surgical repositioning of the distal segment, was significantly correlated with the degree of shift. This result emphasizes the justification of preserving the proximal segment in its exact original anatomic site, in addition to the use of skeletal fixation, to ensure predictable stability after mandibular setback osteotomy. PMID- 2910024 TI - Postretention evaluation of stability and relapse--mandibular arches with generalized spacing. AB - Assessment of cases that had been out of retention a minimum of 10 years and had displayed generalized spacing of anterior teeth before treatment showed consistent reduction of arch length and intercanine width into adult years. Intercanine width constriction typically occurred while arch length decreased in every case, both width and length reduction being progressive with time. Crowding was minimal for the majority of cases; few demonstrated the severe crowding more typical of cases with pretreatment crowding. PMID- 2910025 TI - Reliability of maximum static work efforts by the human masseter muscle. AB - To study the reliability of nonfatiguing maximum voluntary static work efforts by the masseter muscle, six healthy subjects exercised teeth clenching in centric occlusion. Maximum voluntary teeth clenching was performed for 10 seconds on 2 different days, each with two trials, and maximum static work efforts (without artificial feedback-control) were quantified by integrated surface electromyography. Reliability was determined by factorial analyses of variance and intraclass correlations. Data reduction showed that maximum voluntary static work efforts were reproduced reliably during the four different trials. PMID- 2910026 TI - Changes in the maxillary and mandibular tooth size-arch length relationship from early adolescence to early adulthood. A longitudinal study. AB - The purpose of this study was to determine the association between the changes in maxillary and mandibular tooth size-arch length discrepancies (TSALD) and various dentofacial variables for 18 male and 14 female subjects with normal occlusion. All subjects were participants in the Iowa Longitudinal Growth Study and records were evaluated at two stages of dental development: stage I, when the permanent second molars initially erupted into occlusion (X age = 13.3 years); and stage II, at early adulthood (X age = 26.0 years). The following sets of variables were evaluated: mesiodistal crown diameters of single and groups of permanent teeth, dental arch widths and lengths, curve of Spee, maxillary and mandibular anterior and total crowding or spacing, anterior tooth rotations, and various cephalometric dentofacial parameters. Student's t test were used to compare subjects with the most and least changes. Regression analyses also were used to assess the relationships between these parameters and the changes in the maxillary and mandibular tooth size-arch length relationship. The most consistent finding from the t test comparisons is the significantly greater reduction in the available arch length in the group with the most TSALD at early adulthood. No other variables were found to be consistently different in the comparisons between the two groups. The results of the regression analysis indicated that a number of dentofacial variables are associated with the changes in the maxillary and mandibular TSALD--for example, the mesiodistal diameter of different teeth and the changes in anterior and posterior facial heights. The clinical implications of the present findings are discussed. PMID- 2910027 TI - Modeling longitudinal mandibular growth: percentiles for gnathion from 6 to 15 years of age in girls. AB - Growth of the cephalometric landmark gnathion is modeled mathematically with multilevel statistical techniques. The findings, pertaining to a mixed longitudinal sample (N = 772) of 105 girls, 6 to 15 years of age, provide the most accurate descriptions of longitudinal mandibular growth presently available. Polar, rather than rectangular, coordinates are used to better distinguish between the amount and direction of growth. The velocity curve for sella-gnathion includes growth spurts during childhood (7.5 years) and adolescence (12.7 years). Growth direction of gnathion changes regularly throughout the age range, indicating a relative increase of vertical over horizontal growth. These reference standards serve as a basis for comparing and better understanding abnormal growth patterns. PMID- 2910028 TI - The effect of cortisone on the eruption rate of root-resected incisors in the rat. AB - It is generally thought that the periodontal ligament plays a key--perhaps even exclusive--role in tooth eruption. The present study was designed to test the hypothesis that the fundus also may contribute to the process. To this end the effect of cortisone on the eruption rate of root-resected mandibular incisors was examined in male albino rats. Half of the animals received daily injections of cortisone; the other half were given normal saline. Impeded and unimpeded eruption rates were measured at 3-day intervals and tested for between- and among means differences by repeated-measures analysis of variance (ANOVA). In contrast to the acceleration commonly seen in intact incisors, cortisone produced no change in the eruption rate of root-resected incisors. It was concluded therefore that the accelerative effect of cortisone is mediated by the fundus, rather than the periodontal ligament. Further, it is hypothesized that early eruption is controlled by cellular proliferation within the fundus; however, once the tooth enters the oral cavity and becomes functional, the periodontal ligament matures and becomes the dominant factor in subsequent eruption. PMID- 2910029 TI - A comparison of the Ricketts and Tweed-type arch leveling techniques. AB - The purpose of this study was to compare the effectiveness and long-term stability of arch leveling and overbite correction carried out by the Ricketts and modified Tweed techniques. The sample comprised 60 Class II, deep bite, low angle adolescent nonextraction cases, 30 each from the offices of Robert Ricketts and Fred Schudy, with cephalograms taken before and immediately after treatment and an average of more than 4 years after treatment. Both techniques were successful in overbite correction, producing only minimal increases in mandibular plane angle and anterior facial height. Mandibular incisors in the Ricketts group demonstrated more flaring and anterior bodily movement during treatment, with a greater amount of posttreatment uprighting and overbite relapse than the Schudy group. The Ricketts group demonstrated slightly more than 1 mm of true lower incisor intrusion; this change was relatively stable after treatment. Both techniques produced similar amounts of mandibular molar extrusion during treatment; these changes remained stable after treatment. PMID- 2910030 TI - Infection control in orthodontic practice. PMID- 2910031 TI - Attitudes to publicly funded orthodontics in the United Kingdom. PMID- 2910032 TI - Dental education. PMID- 2910033 TI - Why are there no educators with PhD degrees in pediatric departments? PMID- 2910034 TI - Failure of electrocardiographic monitoring to detect cardiac arrest in patients with pacemakers. AB - Two children with cardiac pacemakers are described who experienced cardiorespiratory arrest not detected by the electrocardiographic (ECG) monitor. The pacemaker stimuli were interpreted by the monitor as a QRS complex with inhibition of the heart rate alarm, demonstrating the need for reliable non-ECG monitoring in patients with pacemakers. A review of all deaths in children with pacemakers in the last ten years also shows the high association of respiratory failure in patients with congenital heart disease and a pacemaker, underscoring this need. Various non-ECG monitoring modalities are discussed. Finally, analysis of the ECG monitor characteristics contributing to inappropriate sensing of the pacemaker stimulus was performed, showing the direct relation between the pacemaker stimulus amplitude seen by the monitor and the monitor sensitivity with inappropriate sensing, and the inverse relation between the monitor bandwidth and inappropriate sensing. Recommendations for monitor adjustment when monitoring patients with pacemakers are provided. PMID- 2910036 TI - PhD faculty in the clinical department. PMID- 2910035 TI - Single umbilical artery. A report of 159 cases. AB - We retrospectively reviewed the records of 56,919 infants born from 1966 through 1986 to determine the incidence, significance, and possible associations of single umbilical artery (SUA). One hundred fifty-nine infants were affected. The sex distribution was approximately equal. Fourteen infants (8.8%) were twins who were discordant for SUA. The smallest twin was the one affected in all but two cases. Of the 159 infants, 16 were stillborn and 19 died neonatally. The mean birth weight of all infants with SUA was 2.47 kg, and the mean gestational age was 35.9 weeks. Young primipara and older multipara mothers were more commonly affected. There was an increased incidence of SUA associated with maternal diabetes, epilepsy, toxemia, antepartum hemorrhage, hydramnios, and oligohydramnios. Twenty-six (16.4%) of the associated placentas had anomalies. Seventy-one infants (44.7%) had other congenital malformations. The presence of these malformations was associated with increased mortality. Screening for renal anomalies with ultrasonography or intravenous pyelography was performed in 27 patients and yielded positive results in five (18.5%). We recommend that renal ultrasonography be performed on all infants with SUA. PMID- 2910037 TI - Discretion advised when lowering the serum lipid levels of children. PMID- 2910038 TI - Health status of children in self-care. AB - Are children in self-care more obese, do they miss more school days, and do they make more visits to the school health office than children not in self-care? We undertook a cross-sectional survey of students in ten public elementary schools in Tucson over a two-year period in an attempt to answer these questions. The sample included 503 fifth-grade students, 137 in self-care and 366 not in self care. Demographic information and data on school absences were obtained from school records. Physical examinations were performed at school. Obesity was assessed using the body mass index calculation, in which body mass index = (body weight in kilograms)/(height in meters). Every visit to the school health office during the 1985-1986 and 1986-1987 school years was recorded for each child. There were no differences in age between those in the self-care and adult-care groups. Boys were more likely to be in self-care, as were non-Hispanic children. There were no differences in weight, body mass index, school days missed, or visits to the school health office between children in self-care and those in adult care. Our findings suggest that, by the criteria used in this study, 11 year-old children in self-care do not suffer more ill health than their counterparts in adult care. PMID- 2910039 TI - Diagnostic value of testosterone therapy in boys with delayed puberty. AB - A brief course of testosterone injections is known to be an effective treatment for boys with constitutional delayed puberty. In this study, data from seven boys at least 14 years old who received testosterone enanthate (100 mg intramuscularly monthly for four months) were analyzed to see if linear and testicular growth responses could be useful diagnostically in excluding growth hormone deficiency (GHD) and isolated gonadotropin deficiency, two conditions that are often difficult to distinguish from constitutional delayed puberty. During four months of testosterone therapy, growth rate increased from 4.0 +/- 1.0 cm/y to 10.7 +/- 2.3 cm/y, and was greater than 8 cm/y in all patients. Since testosterone-induced stimulation of linear growth is largely GH-mediated, the large increase in growth rate in all boys is considered indicative of GH sufficiency. Testis length, which did not increase during testosterone therapy, increased by 0.6 to 0.8 cm in every patient (from 2.7 +/- 0.3 cm to 3.4 +/- 0.4 cm) over the following four months, indicating normal gonadotropin secretion and normal pubertal progression; in contrast, the increase in serum testosterone concentrations after discontinuation of testosterone treatment was more variable. It is concluded that the growth response to a four-month course of testosterone is helpful in excluding GHD in boys with delayed puberty, and an additional four months of follow-up is sufficient to document the onset of puberty, thereby eliminating the possibility of isolated gonadotropin deficiency. PMID- 2910040 TI - Ectrodactyly, ectodermal dysplasia, and clefting associated with thymic aplasia. PMID- 2910041 TI - Reprint requests. How and why they were made. AB - Of the 457 reprint requests that I received over a two-year period, 432 (94.5%) came in the form of preprinted postcards and the remainder came in the form of letters. Only 235 (51.4%) were signed. There were 450 (98.5%) requests for one copy of the article and seven (1.5%) requests for more than one copy. Three hundred ninety-five (86.4%) requests were for one article, and 62 (13.6%) requests were also for any other previous articles on the subject. None of the reprint requests arrived with a self-addressed stamped envelope. One hundred twenty-seven (27.8%) requests came with a return address stick-on label. Most reprint requests were in English and came from the United States and countries in eastern Europe. A questionnaire was sent to each of the 457 persons who requested a reprint to determine how and why the request was made. There were 259 (56.7%) replies available for analysis. One hundred ninety-three (74.5%) reprint requests were made by the individuals requesting the reprint and 59 (22.8%) were made by their secretaries. The majority (81.1%) learned about the article and address from Current Contents. Forty-four (17%) had read the article (or abstract) before the reprint request was made. The two most common reasons given for the request were the unavailability of the journal and the high quality of the reprint. Two hundred fifty-six (98.8%) of the persons requesting reprints found them very useful. PMID- 2910042 TI - Passive freebase cocaine ('crack') inhalation by infants and toddlers. AB - Cocaine and its principal metabolite, benzoyl ecgonine, were isolated from the urine of four hospitalized children who had been exposed to the smoke of freebase cocaine ("crack") used by their adult caretakers. Two of the children had transient neurological symptoms (drowsiness and unsteady gait) and two had seizures whose cause could not be determined by laboratory investigation. Passive cocaine inhalation may have caused or contributed to these symptoms. Children in the care of adults who abuse freebase cocaine should be considered at risk not only for disruption of their social environment but also for the effects of cocaine toxicity. PMID- 2910043 TI - Haemophilus B polysaccharide vaccine. Antibody kinetics in 17- to 71-month-old children. AB - The antibody response to polysaccharide vaccines is well known to be age variable, with younger infants or children responding less dependably and with lower antibody levels. The fate of these induced antibodies over time is less well understood. We studied the antibody kinetics of beta-Capsa 1, a Haemophilus B polysaccharide vaccine, in 185 children aged 17 to 71 months. Ninety percent of the children vaccinated at age 2 years or older achieved reportedly immune serum antibody levels three weeks after vaccination; 45% vaccinated at age 18 months achieved such levels. In six months, the antibody levels fell significantly in all children. In those vaccinated at age 18 months, the levels six months after vaccination were not significantly different from those prior to vaccination. Our study raises the possibility that antibody kinetics may be as critical a consideration as immediate antibody response in deciding the proper clinical use of a polysaccharide-based vaccine. PMID- 2910044 TI - Epidemic methicillin-gentamicin-resistant Staphylococcus aureus in a neonatal intensive care unit. AB - Between October 1985 and August 1986, 49 isolates of methicillin-resistant Staphylococcus aureus (MRSA) were obtained from 26 neonates in the neonatal intensive care unit (NICU) at the Medical University Hospital, Charleston, SC. Sites of MRSA isolation were the respiratory tract (33%); nasopharynx (12%); gastrointestinal tract (12%); eye (8%); blood (6%); and catheter tips, wounds, or umbilicus (29%). Very low birth weight was a significant risk factor for MRSA acquisition. All isolates had the same phage type (47/54/75/83A), antibiogram, and whole-cell protein profile. Agarose gel electrophoresis of all 49 isolates disclosed a plasmid level of approximately 45 X 106 daltons (45 megadaltons) in ten different isolates and no plasmid DNA in 39 isolates. Cultures of NICU personnel failed to disclose MRSA carriers and environmental cultures for MRSA were negative. Ten selected isolates showed lower minimal bactericidal concentrations for hexachlorophene than for chlorhexidine. Standard infection control measures such as contact isolation, hand washing with chlorhexidine, and cohorting (when possible) failed to contain the epidemic. Ultimately, eradication of MRSA from the NICU was associated with the institution of hexachlorophene hand washing. PMID- 2910045 TI - Psychosocial determinants of compliance in adolescents with iron deficiency. AB - The relationship between selected psychosocial variables and compliance was studied in 71 adolescents prescribed medication for iron deficiency. The mean compliance rate in the study group was 67%. Home pill counts were highly correlated with the other methods of measuring compliance, ie, change in serum ferritin level and urinary assay for tracer riboflavin. Statistically significant predictors of compliance included adverse side effects, initial estimate by the adolescent as to his probable level of compliance, and frequency of family reminders to take the medication. There was no significant correlation between self-esteem, locus of control, or most variables of the Health Belief Model and the level of patient compliance. Our findings suggest that home pill counts are an accurate method of assessing compliance and that instituting family reminders may be helpful in those adolescents who are potentially non-compliant. PMID- 2910046 TI - Household electrical injuries in children. Epidemiology and identification of avoidable hazards. AB - The medical records of all children with household electrical injuries were reviewed. The children were seen from 1980 to 1986 at The Children's Hospital of Philadelphia and The Johns Hopkins Hospital, Baltimore. Injuries occurred predominantly in children younger than age 6 years, most commonly while meals were being prepared. The most frequent cause of injury was oral contact with electrical cords or cord sockets, or contact with wall sockets either directly or via conductive foreign objects such as keys or pins. Data reported to the Consumer Product Safety Commission were also analyzed and corroborated our findings. We suggest a series of prevention strategies based on these data. A new wall outlet cover design is described. PMID- 2910047 TI - Differential effects of intrauterine and postnatal brain growth failure in infants of very low birth weight. AB - We investigated the contribution of brain growth failure to outcome in infants of very low birth weight (VLBW; less than 1.5 kg) who were appropriate for gestational age (AGA; n = 379) or small for gestational age (SGA; n = 102). Growth was assessed at birth, term, and 8 and 20 months' corrected age and results of a Bayley Mental Developmental Index (MDI) and neurologic examination were evaluated at 20 months of age. Both groups had similar 20-month MDI scores (93 vs 90) and similar rates of neurologic impairment (14% vs 10%). More SGA infants (25%) than AGA infants (14%) had a subnormal head circumference at 8 months' corrected age, indicating failure to catch up in head growth. Subnormal head size at 8 months predicted the 20-month MDI score for both groups. However, multivariate analysis indicated that, whereas subnormal 8-month head size was directly associated with the MDI score in AGA children, in SGA children 8-month head size was not significantly related to the MDI score when neonatal illness, neurologic impairment, socioeconomic status, and race were controlled for. We conclude that in AGA VLBW infants, subnormal head size at 8 months results from major neonatal illness and has adverse later effects. In SGA infants, subnormal head size at 8 months has many causes, including growth retardation in utero, which may not have an adverse effect on outcome; if subnormal head size is superimposed with neonatal illness, a poorer outcome is likely. PMID- 2910048 TI - The pediatrician as a consultant. AB - The time has come for pediatricians to assert themselves as consultants. They should be able to take care of most illnesses and children. The pediatrician should decide when help by a subspecialist is needed. The parents should not be expected to be the "brokers" for various specialty services. A tentative list of conditions every pediatrician should be able to handle with confidence is included. PMID- 2910049 TI - Otologic manifestations in congenital velopharyngeal insufficiency. AB - A study of ear disease in children with congenital velopharyngeal insufficiency (VPI) was undertaken. A retrospective chart analysis of 80 cases of VPI formed the basis of this review. Thirty-seven percent of the children had evidence of middle ear disease, with middle ear effusion and recurrent otitis media being the most frequent findings. Thirty-one percent had abnormal audiograms, with 20% having a conductive or mixed hearing loss. Overall, 46% of the children had otologic manifestations, indicating the need for the pediatrician and the otolaryngologist together to be actively involved in the evaluation and treatment of this group of children, starting in early infancy. PMID- 2910050 TI - Pulmonary function in preterm infants following treatment with intravenous indomethacin. AB - Pulmonary function tests, including measurements of arterial blood gas levels, total pulmonary compliance, and arterial-alveolar oxygen ratios, were performed in 38 ventilator-dependent preterm infants with respiratory distress syndrome who weighed less than 1500 g at birth. Twenty-seven had a physiologically significant patent ductus arteriosus (PDA). Twelve were assigned at random to receive three doses of intravenous indomethacin, 0.2 mg/kg per dose, on the fourth day of life. This treatment resulted in ductal closure in seven infants by the seventh day of life. Another concurrently observed group of 15 infants with PDA received no indomethacin. A third group of 11 infants lacked evidence of a PDA. Pulmonary function in the infants who received indomethacin did not differ significantly from that in the other two groups. PMID- 2910051 TI - Reported sexual behaviors and self-esteem among young adolescents. AB - Six hundred seventy-seven adolescents in grades 7 through 9 of a blue-collar, midwestern junior high school responded to a survey of sexual behavior and self esteem. The focus of this study was on the relationship between sexual experience and self-esteem. Fifty-five percent of the students reported having had at least one coital experience; 7% reported having intercourse about once a week. The proportion of sexually experienced adolescents increased with age; 28% of 12-year olds, 52.7% of 13-year-olds, 60.1% of 14-year-olds, 73.6% of 15-year-olds, and 90% of 16-year-olds reported having intercourse on at least one occasion. More boys of all ages were sexually active than girls. Six percent of students had had, or were suspicious of having had, a sexually transmitted disease; 7.8% were involved in a pregnancy. The average of the self-esteem scores for girls was significantly lower than the average for boys. There was an interaction effect between gender and coital history for self-esteem. Girls who reported having had intercourse had lower self-esteem scores than those who did not. On the other hand, self-esteem of sexually experienced and inexperienced boys did not differ, nor did self-esteem of virginal boys and girls. Boys and girls with a history of sexually transmitted diseases had lower self-esteem than all others. Pregnancy, on the other hand, did not seem to affect self-esteem of the sexually experienced adolescents. This cross-sectional study does not permit determination of whether the lower average self-esteem among certain girls was antecedent to or a consequence of sexual experience. PMID- 2910052 TI - Radiological case of the month. Pneumomediastinum and subcutaneous emphysema caused by diabetic hyperpnea. PMID- 2910053 TI - Safety of newborn discharge in less than 36 hours in an indigent population. AB - The safety of a moderately early newborn discharge program and the ability to follow up within 48 hours of release was evaluated in an indigent population from our institution. A retrospective chart review of 2000 consecutive admissions to our normal newborn nursery was conducted to determine the following: (1) length of nursery stay; (2) reason for extension of nursery stay beyond 36 hours; (3) documentation of outpatient follow-up within 48 hours of discharge for infants released within 36 hours of birth; and (4) incidence of and reason for readmission to the hospital within one week of initial discharge. A total of 1091 infants (54.6%) were discharged within 24 to 36 hours of birth, with documentation of outpatient follow-up in 994 (91.1%). Twenty-five (2.3%) of the early discharges required readmission within seven days of initial discharge compared with a 0.89% incidence among infants hospitalized greater than 48 hours. Twenty-four of the 25 readmissions did have outpatient follow-up, and no serious complications occurred. The data demonstrate that moderately early neonatal discharge can be safely accomplished in an indigent population with the aid of a successful outpatient follow-up program. PMID- 2910054 TI - Regression of Q waves following acute myocardial infarction. AB - The predictors and effects of Q wave regression following acute Q wave myocardial infarction were examined in 1965-1982 in 127 Japanese-American men who participated in a prospective epidemiologic study of cardiovascular disease. Of these 127 men, 53 (42%) showed total regression of Q waves, 17 (13%) showed partial regression, and 57 (45%) showed no Q wave regression following acute myocardial infarction. Age at myocardial infarction and location of myocardial infarction did not predict which men would undergo Q wave regression. Q wave status after myocardial infarction (total, partial, or no regression) did not predict survival or recurrence of myocardial infarction. This study found that a substantial proportion of acute myocardial infarction cases undergo Q wave regression, indicating that clinicians and investigators alike require additional evidence to identify people with previous myocardial infarction. PMID- 2910055 TI - A comparison of several measures of exposure to arsenic. Matched case-control study of copper smelter employees. AB - To explore the relation between respiratory cancer mortality and exposure to airborne arsenic, methods of conditional logistic regression analysis are applied to a matched case-control study of copper smelter employees in Montana. With follow-up data for the period 1938-1977, several measures of arsenic exposure are compared. For men first employed prior to 1925, three measures--the category of maximum arsenic exposure, cumulative arsenic exposure, and time-weighted average arsenic exposure--are good predictors of respiratory cancer mortality. Within this group, there was a significantly elevated relative risk of respiratory cancer mortality associated with medium and heavy exposure to arsenic. For men first employed during 1925-1947, time-weighted average exposure to arsenic (adjusted for age at first employment) is the best predictor. In this group, men with heavy arsenic exposure and initially employed at 16.9 years had a relative risk of 6.0 in comparison to the baseline group with only light exposure to arsenic and initially employed at 31.9 years. No particular advantage is found in lagging exposures 10 years prior to death of the case in each matched set. PMID- 2910056 TI - The impact of confounder selection criteria on effect estimation. AB - Much controversy exists regarding proper methods for the selection of variables in confounder control. Many authors condemn any use of significance testing, some encourage such testing, and other propose a mixed approach. This paper presents the results of a Monte Carlo simulation of several confounder selection criteria, including change-in-estimate and collapsibility test criteria. The methods are compared with respect to their impact on inferences regarding the study factor's effect, as measured by test size and power, bias, mean-squared error, and confidence interval coverage rates. In situations in which the best decision (of whether or not to adjust) is not always obvious, the change-in-estimate criterion tends to be superior, though significance testing methods can perform acceptably if their significance levels are set much higher than conventional levels (to values of 0.20 or more). PMID- 2910057 TI - Hepatitis A outbreak on a floating restaurant in Florida, 1986. AB - In April and May 1986, the largest reported foodborne outbreak of hepatitis A in Florida state history occurred among patrons and employees of a floating restaurant. A total of 103 cases (97 patrons and six employees) were identified. The exposure period lasted 31 days (March 20-April 19), making this the most prolonged hepatitis A outbreak to occur in a restaurant that to date has been reported to the Centers for Disease Control. The exposure period was divided into time intervals (peak, early, late, and total) for calculation of food-specific attack rates. The authors showed that green salad was an important vehicle of transmission for each phase of the exposure period, with the highest adjusted odds ratio for the three-day peak exposure interval (March 28-30), 6.8 (p = 0.001). Non-salad pantry items and mixed bar drinks were also identified as vehicles of transmission; both were more important during the early interval of the exposure period than during the late interval. Two of six infected employees worked in the pantry and may have sequentially infected patrons. Though rare, this outbreak suggests that hepatitis A infection among employees may allow for transmission to patrons for prolonged periods of time. Prevention of such outbreaks requires prompt reporting of ill patrons with rapid identification of infected employees and correction of food handling practices. PMID- 2910058 TI - An explosive point-source measles outbreak in a highly vaccinated population. Modes of transmission and risk factors for disease. AB - In 1985, 69 secondary cases, all in one generation, occurred in an Illinois high school after exposure to a vigorously coughing index case. The school's 1,873 students had a pre-outbreak vaccination level of 99.7% by school records. The authors studied the mode of transmission and the risk factors for disease in this unusual outbreak. There were no school assemblies and little or no air recirculation during the schooldays that exposure occurred. Contact interviews were completed with 58 secondary cases (84%); only 11 secondary cases (19%) of these may have had exposure to the index case in the classrooms, buses, or out of school. With the use of the Reed-Frost epidemic model, only 22-65% of the secondary cases were likely to have had at least one person-to-person contact with the index case during class exchanges, suggesting that this mode of transmission alone could not explain this outbreak. A comparison of the first 45 cases and 90 matched controls suggested that cases were less likely than controls to have provider-verifiable school vaccination records (odds ratio (OR) = 8.1) and more likely to have been vaccinated at less than age 12 months (OR = 8.6) or at age 12-14 months (OR = 7.0). Despite high vaccination levels, explosive measles outbreaks may occur in secondary schools due to 1) airborne measles transmission, 2) high contact rates, 3) inaccurate school vaccination records, or 4) inadequate immunity from vaccinations at younger ages. PMID- 2910059 TI - On the measurement of susceptibility in epidemiologic studies. AB - Although relative effects of risk factors (relative risks) are commonly used in epidemiologic studies of disease, these measures do not provide estimates of the proportion of persons who are "susceptible" to the risk factor. Susceptibility may be defined under a simple sufficient cause model as the underlying factor (or set of factors) sufficient to make a person contract a disease following exposure. The authors derive simple estimates of the proportion of susceptibles in a population based on relative risk, and disease and exposure frequencies. The proportion of susceptibles increases with increasing disease frequency and relative risk but declines at high exposure frequency. For many chronic diseases with a lifetime risk in the range of 1-10 per cent, rare exposures suggest the presence of a large proportion of susceptibles, whereas common exposures suggest fewer susceptibles in the population. The estimation of the proportion of susceptibles is important in the search for genetic and environmental factors that interact with measured risk factors in etiologic studies of disease. PMID- 2910060 TI - The basis for interpreting family history. PMID- 2910061 TI - Ordinal regression models for epidemiologic data. AB - Health status is often measured in epidemiologic studies on an ordinal scale, but data of this type are generally reduced for analysis to a single dichotomy. Several statistical models have been developed to make full use of information in ordinal response data, but have not been much used in analyzing epidemiologic studies. The authors discuss two of these statistical models--the cumulative odds model and the continuation ratio model. They may be interpreted in terms of odds ratios, can account for confounding variables, have clear and testable assumptions, and have parameters that may be estimated and hypotheses that may be tested using available statistical packages. However, calculations of asymptotic relative efficiency and results of simulations showed that simple logistic regression applied to dichotomized responses can in some realistic situations have more than 75% of the efficiency of ordinal regression models, but only if the ordinal scale is collapsed into a dichotomy close to the optimal point. The application of the proposed models to data from a study of chest x-rays of workers exposed to mineral fibers confirmed that they are easy to use and interpret, but gave results quite similar to those obtained using simple logistic regression after dichotomizing outcome in the conventional way. PMID- 2910062 TI - A program to calculate sample size, power, and least detectable relative risk using a programmable calculator. AB - A program for the Hewlett Packard 41 series programmable calculator that determines sample size, power, and least detectable relative risk for comparative studies with independent groups is described. The user may specify any ratio of cases to controls (or exposed to unexposed subjects) and, if calculating least detectable relative risks, may specify whether the study is a case-control or cohort study. PMID- 2910063 TI - A computer program for incidence density sampling of controls in case-control studies nested within occupational cohort studies. AB - A nested case-control study is a case-control study performed with a cohort study. The nested case-control design is useful because the number of study subjects for whom risk factor information is needed is smaller than in the original cohort study. The approach is especially helpful when collection of data is expensive or time consuming, as when it is necessary to contact subjects or next of kin. Selection of controls in nested case-control studies is best performed with a method called "incidence density" sampling. An approach to incidence density sampling that yields a valid estimate of the rate ratio is sampling without replacement from noncases at the time of case occurrence. To implement this approach, a system of computer programs was written that randomly selects a user defined number of controls for each case. The case-control data produced by this program can be analyzed by conditional logistic regression. PMID- 2910064 TI - Fetal loss associated with two seasonal sources of electromagnetic field exposure. AB - We have studied two sources of electromagnetic fields where exposure is highly seasonal (ceiling cable electric heat and electrically heated beds). Because many potential confounders could not be addressed, we can make no valid statement about overall differences in abortion rates between those exposed and those not exposed to these seasonal sources. However, by analyzing seasonal trends, we have minimized the problem of unaddressed confounders because we did not look at a difference between the user and nonuser groups, but rather at a difference within the user group during months of higher exposure compared with months of lower exposure. Thus, each user group provides its own control. The function of the nonuser control group is simply to assure that any seasonal trend found in the user group is not just a general seasonal variation in reported fetal loss that can be found equally well in the nonuser population. Using this technique, we found that each user group reported fetal loss disproportionately often during the season when electromagnetic field exposure was increasing. PMID- 2910065 TI - Re: "Statistical modelling of lung cancer and laryngeal cancer incidence in Scotland, 1960-1979". PMID- 2910066 TI - Re: "Effects of passive smoking in the Multiple Risk Factor Intervention Trial". PMID- 2910067 TI - Re: "US prevalence of occupational pleural thickening: a look at chest x-rays from the first National Health and Nutrition Examination Survey". PMID- 2910068 TI - Assessment of the working lifetime risk of exposure in an occupational cohort. PMID- 2910069 TI - Age, period, and cohort models. Non-overlapping cohorts don't resolve the identification problem. AB - Age, period, and cohort models have generally been applied to rates from tabulated national statistics, and it is known that such models suffer from an identification problem. When individual records, including date of birth, are available, however, a unique solution has been proposed which uses non overlapping cohorts. We have shown that the identification problem exists in continuous time, so that even perfect information on the three variables will fail to resolve it. It is important to recognize clearly the assumptions that are implicit in the non-overlapping cohort formulation of the age-period-cohort model. The value of the solution proposed depends critically on their appropriateness or otherwise. It should always be remembered that the assumptions determine much of the final solution, including the apportionment of trend to the different components, age, period, or cohort. PMID- 2910070 TI - Cigarette smoking and breast cancer. AB - The relation between cigarette smoking and the risk of breast cancer in women was investigated in a population-based case-control study conducted in Adelaide, Australia during 1982-1984. Cases were identified through the South Australian Central Cancer Registry, and, for each case, one age-matched control was selected from the electoral register; in all, 451 case-control pairs were enrolled. Overall, no clear association was found between ever or current smoking and breast cancer risk. In a subgroup analysis, premenopausal ex-smokers were observed to have an increased risk (estimated odds ratio = 2.3). The absence of a protective effect of cigarette smoking on breast cancer risk may reflect the relatively weak estrogen dependence of breast cancer, or the nature of its hormone dependence. PMID- 2910071 TI - Precursors of essential hypertension. The role of body fat distribution pattern. AB - Progression from normotension between 1964 and 1972 to essential hypertension by age 55 years was documented in 1,031 adult members of the Kaiser Permanente Medical Care Program (Northern California region) from computerized multiphasic health checkup records and medical record review. Each case was matched to a persistently normotensive control on age, sex, race, number, and dates of multiphasics. In 609 pairs with baseline measurements of subscapular and triceps skinfolds, mean interval from baseline to the case's first hypertensive multiphasic was 5.7 years, and mean age at onset of hypertension was 47 years. Baseline measures of body mass index, subscapular skinfold, and triceps skinfold were each predictive of development of hypertension (odds ratios 3.85, 3.75, and 2.29 respectively, comparing highest with lowest quintiles, p less than 0.0001 for each). When both skinfolds were included in the same model, subscapular skinfold was highly predictive and triceps skinfold was no longer related to risk. When the authors controlled for overall obesity (body mass index), subscapular skinfold remained highly predictive (p less than 0.0001). In 330 pairs who also had skinfold measurements at the hypertensive multiphasic, weight gain was a strong predictor of hypertension. Increase in subscapular skinfold conferred a small increase in risk in women only. The authors conclude that centrally deposited body fat increases risk for developing essential hypertension independent of the overall level of obesity, while peripherally deposited fat does not. PMID- 2910072 TI - Marital status and mortality in middle-aged Swedish men. AB - In a large primary prevention trial among middle-aged men in Gothenburg, Sweden, register data were used to establish marital status, alcohol abuse, and economic problems for nearly all of the study population in 1970-1973. Married men had a higher participation rate in the examinations for the trial than non-married men, with non-married alcoholic men having the lowest participation rates. Among the participants, 26% of divorced men, but only 5% of married men were registered with the social authorities for alcohol problems. Serum cholesterol, body mass index, and diabetes were not associated with marital status, but smoking was more common among widowers and divorced men. Nonfatal myocardial infarction was not related to marital status among participants, after a mean follow-up of 11.8 years. Death from coronary heart disease was more common in non-married men in univariate analysis, but not when other risk factors were taken into consideration. In participants, married men had a mortality rate of 9%, compared with 20% for divorced men. After adjustment for other risk factors, including registration for alcohol problems, smoking, and occupational class, the association between marital status and total mortality was still highly significant. Among nonparticipants in the trial, 13% of married men were registered for alcohol problems, compared with 41% of divorced men. Nonparticipants had higher all-cause mortality, 18% for married men and 33% for divorced men. PMID- 2910073 TI - An investigation of report bias in a case-control study of pregnancy outcome. AB - The role of report (recall) bias in case-control studies of possible reproductive hazards was investigated in a study of women who gave birth at the Royal Victoria Hospital, Montreal from September 1983 to May 1985. Women were questioned twice (early in pregnancy; after delivery) about exposures that might influence pregnancy outcome. The two sets of responses of case mothers, control mothers, and mothers of infants of intermediate health status were then compared. Similar inconsistencies in the reporting of 39 exposure variables were common in all three groups, with postdelivery deletion of previous reports more frequent than addition of new information. Changes in reporting were not associated with pregnancy outcome, maternal concern about the baby or maternal sociodemographic characteristics. Odds ratios of exposure estimated from the two sets of data did not differ importantly. Moreover, there was no postdelivery trend to increases, or decreases, in the estimates of the odds ratios. The data do not provide evidence of biased reporting of exposures. PMID- 2910074 TI - Leisure time physical activity in the Framingham Offspring Study. Description, seasonal variation, and risk factor correlates. AB - Self-reported leisure time physical activity was analyzed for 1,598 men and 1,762 women aged 20-69 years in the Framingham Offspring Cycle 2 exam in 1979-1983. Walking for pleasure was generally the most common physical activity for both sexes throughout the year. Substantial seasonal variation was noted for the most common activities: gardening, carpentry, lawn mowing, golf, and running for men; and gardening, swimming, health club exercise, dancing, and bicycling for women. Both sexes expended more kilocalories in physical activities in summer than in winter (p less than 0.001). Frequency of participation in activities sufficient to induce perspiration was associated with frequency of participation in at least one hour of conditioning (greater than or equal to 7.5 kilocal/minute) activities per week (p less than 0.001). Based on age-adjusted mean levels, higher high density lipoprotein cholesterol, lower heart rate, lower body mass index and fewer cigarettes smoked per day were consistently observed across four quartiles of increasing physical activity levels (p less than 0.01). Men who participated in at least one hour of conditioning activities per week had significantly different mean levels for these four risk factors than men who reported less than one hour of such activities per week (p less than 0.001). Results substantiate previous reports of an inverse relation between physical activity levels and cardiovascular risk, and suggest seasonal variation in activity levels should be considered in future studies which explore the relation between physical activity and cardiovascular disease. PMID- 2910075 TI - Age-related change in anti-carbohydrate antibody levels. AB - It has been proposed that immunity declines with age. Most evidence for this hypothesis has been obtained from cross-sectional samples of unrelated populations that differ in age, antigen exposure, and morbidity. In the present study, the authors used serum samples collected repeatedly from the same persons in longitudinal studies. Two representative samples of the population in Goteborg, Sweden were obtained; the first was studied at ages 38, 50, and 62 years, and the second at ages 70, 75, 79, and 81 years, respectively. The phosphorylcholine determinant of pneumococcal teichoic acid and the B blood group determinant were selected as model polysaccharide antigens. The results demonstrate a consistent decline in individual antibody levels in the decades before age 70 years but not later. Antibodies to phosphorylcholine and blood group B were highly parallel, suggesting that the decline was a general phenomenon for antibodies to polysaccharide antigens. PMID- 2910076 TI - Pulmonary function as a predictor of coronary heart disease. AB - The role of pulmonary function as an independent predictor of coronary heart disease was examined in 1965-1983 in a cohort of Japanese-American men. As part of the Honolulu Heart Program, the authors measured pulmonary function in 5,924 men aged 45-68 years who were free of coronary heart disease at baseline examination and followed them for 15-18 years for the development of nonfatal myocardial infarction and fatal coronary heart disease. Per cent predicted forced expiratory volume in one second (%PFEV1) was significantly inversely related to coronary heart disease incidence in the total cohort after adjusting for age (p less than 0.0001) and then for all known coronary heart disease risk factors (p = 0.0004). However, when examined by smoking status, %PFEV1 was a predictor of coronary heart disease only among past and current smokers, and not for men who had never smoked cigarettes (p = 0.36). The association between pulmonary function and coronary heart disease can be explained by cigarette smoking, which leads to both lung impairment and coronary heart disease incidence. PMID- 2910077 TI - Hemoglobin Southampton (Casper): characterization of the base mutation. AB - Hemoglobin Casper is characterized by the substitution of cytidine for thymidine in condon 106 of the beta globin gene. This substitution results in the creation of a new restriction site for Msp I but not for the isoschizimer Hpa II. The restriction pattern following digestion with Msp I reveals a 9.9-kb fragment not seen in normal individuals or following digestion of Casper DNA with Hpa II. This finding confirms the predicted base mutation and indicates that the cytidine in the newly acquired CpG site is methylated. PMID- 2910078 TI - Biochemical assays of hemoglobin in normal human erythroid clones. AB - Quantitation of small amounts (2-3 micrograms) of hemoglobin (Hb) was achieved by each of three spectrophotometric techniques. An assay employing benzidine base consistently underestimated Hb at this level and gave a wide scatter of results at higher values. The cyanmethemoglobin method was at the limit of its sensitivity and suffers from the disadvantage of having high optical densities in the blank samples. By contrast, pyridine hemochromogen can be detected accurately with 200 ng of Hb (equivalent of 6,000 mature erythrocytes), and the regression line with this technique virtually passes through the origin. Furthermore, the extinction coefficient of pyridine hemochromogen in the Soret band is 13.5-fold greater than that of cyanmethemoglobin. In normal human erythroid clones, generated in vitro from bone marrow cells, mean cell hemoglobin (MCH) values were determined after various intervals of culture. The MCH after 5, 7, 10, and 14 days were 11.8, 15.8, 26.6, and 34.4 pg, respectively, by the pyridine hemochromogen method. Reaction product was also identified in granulocyte macrophage clones, presumably reflecting the content of other heme proteins such as catalase and cytochromes. Account must be taken of this non-Hb material in computing true MCH values for erythroid cells. PMID- 2910079 TI - Ovarian relapse in a young woman with acute lymphoblastic leukaemia. AB - Bilateral ovarian relapse in a young woman with acute lymphoblastic leukaemia (ALL) was treated by oophorectomy and intensive chemotherapy. She remains well off therapy 97 months following diagnosis and 45 months from ovarian relapse. PMID- 2910080 TI - Validation of survival-predictive models in myelodysplastic syndromes. PMID- 2910081 TI - Myelodysplastic syndrome and secondary acute leukemia after treatment of essential thrombocythemia with melphalan. PMID- 2910082 TI - Brucellosis and sinus histiocytosis with massive lymphadenopathy. PMID- 2910083 TI - Leukemic synovitis. PMID- 2910084 TI - Theophylline toxicity subsequent to ranitidine administration: a possible drug drug interaction. PMID- 2910085 TI - Low-dose amiodarone-induced pneumonitis: evidence of an immunologic pathogenetic mechanism. PMID- 2910086 TI - Carcinoma of the colon presenting as Streptococcus equinus bacteremia. PMID- 2910087 TI - Streptomycin-induced fever confirmed by rechallenge. PMID- 2910088 TI - Diarrhea in patients infected with the human immunodeficiency virus. PMID- 2910089 TI - Progressive disseminated histoplasmosis in patients with acquired immunodeficiency syndrome. PMID- 2910090 TI - Treatment of antibiotic-associated Clostridium difficile colitis with oral vancomycin: comparison of two dosage regimens. AB - PURPOSE: High-dose (500 mg orally four times daily) vancomycin is considered by many investigators to be the most effective treatment for antibiotic-associated Clostridium difficile colitis. However, a lower dosage of 125 or 150 mg given three or four times a day has become popular, has been shown to be effective, and is less expensive than the high-dose regimen. We therefore decided to compare two vancomycin dosage regimens in a randomized trial. PATIENTS AND METHODS: The study involved 46 hospitalized patients with serious underlying diseases complicated by C. difficile diarrhea or colitis. Patients were assigned (according to a table of random numbers) to treatment with either 125 or 500 mg of vancomycin orally four times daily for an average of 10 days. RESULTS: No significant differences in measurable responses to the two regimens were noted. There were no treatment failures. The mean duration of diarrhea after initiation of therapy was about four days, and almost all patients had no diarrhea after one week. The organism continued to be demonstrated in the stools of about 50 percent of patients for the first few weeks after completion of therapy, and nine (20 percent) patients developed a recurrence of their diarrheal illness. Vancomycin was well tolerated by all patients. CONCLUSION: Since the dose of 125 mg appeared to be as effective as the 500-mg dose, which is more expensive, the 125-mg dose is preferred when vancomycin is used in treatment of this disease, unless the patient is critically ill. PMID- 2910091 TI - Prediction of amiodarone-induced pulmonary toxicity. PMID- 2910093 TI - Esophageal dysfunction and chest pain in patients with mitral valve prolapse: a prospective study utilizing provocative testing during esophageal manometry. AB - PURPOSE: The cause of chest discomfort in patients with mitral valve prolapse (MVP) remains unknown. Our aim was to determine prospectively the incidence of esophageal disorders and abnormal responses to edrophonium chloride and esophageal acid infusions in patients with MVP and troublesome non-ischemic chest pain. PATIENTS AND METHODS: After coronary artery disease was excluded, 20 patients with MVP and chest pain underwent esophageal manometry and provocative testing with edrophonium chloride and acid infusion. Seven patients with MVP but without chest pain served as control subjects; they also underwent esophageal manometry with provocative testing. RESULTS: Esophageal manometry revealed esophageal disorders in 16 patients: diffuse esophageal spasm in 14 patients, nutcracker esophagus in one, and hypotensive lower esophageal sphincter in one. Esophageal motility was normal in four patients. Injection of edrophonium and acid infusion tests evoked typical chest discomfort in three of 18 and five of 19 patients, respectively. In six of seven control subjects with MVP but with no chest discomfort, esophageal motility was normal and provocative testing did not produce chest discomfort (p less than 0.05 versus results in patients). CONCLUSION: Esophageal disorders were common and may account for chest discomfort in certain patients with MVP and persistent chest pain syndromes. PMID- 2910092 TI - Hypertriglyceridemia in the acquired immunodeficiency syndrome. AB - PURPOSE: A relationship between the induction of hypertriglyceridemia by cytokines and the cachexia seen in chronic infection has been proposed by other investigators. Since patients with the acquired immunodeficiency syndrome (AIDS) often experience progressive tissue wasting, we decided to examine serum lipid levels and body cell mass in patients with AIDS. PATIENTS AND METHODS: Serum lipid levels and body cell mass were measured in 32 patients with the acquired immunodeficiency syndrome (AIDS), eight asymptomatic subjects who were anti-human immunodeficiency virus (HIV) antibody positive, and 17 heterosexual and homosexual control subjects who did not have antibodies to HIV. RESULTS: Mean triglyceride concentrations and the prevalence of hypertriglyceridemia (50 percent) were significantly increased in patients with AIDS compared with control subjects (p less than 0.002 and p less than 0.005, respectively), whereas the mean triglyceride levels of HIV-positive subjects were intermediate. There were no differences in cholesterol levels among the three groups. Using total body potassium adjusted for height and age (KHT) as a measure of body cell mass, 16 of 32 patients with AIDS but none of the HIV-positive or control subjects had significant depletion of body cell mass. There was no direct relationship between triglyceride levels and KHT among AIDS or HIV-positive subjects. In patients with AIDS, mean triglyceride levels and the prevalence of hypertriglyceridemia were similar in the presence and absence of wasting. CONCLUSION: Hypertriglyceridemia is a common finding in AIDS and is independent of the degree of wasting. PMID- 2910094 TI - Increased serum cortisol binding in chronic active hepatitis. AB - PURPOSE: A high serum cortisol concentration, apparently due to increased cortisol-binding globulin (CBG), was found in a patient (index case) with chronic active hepatitis (CAH). We therefore performed further studies to determine whether increased cortisol binding is generally associated with CAH. PATIENTS AND METHODS: Serum samples were obtained from 15 hospitalized patients with long-term liver function test elevations but no evidence of cirrhosis, 15 normal subjects without a history of hepatitis, four healthy pregnant women, and 10 alcoholic patients with stigmata of cirrhosis. Serum cortisol binding was measured by an adaptation of a previously described charcoal uptake method. Thyroxine-binding globulin (TBG) and sex hormone-binding globulin were determined by radioimmunoassays. RESULTS AND CONCLUSION: Charcoal uptake of 125I cortisol from sera of normal subjects and additional patients with CAH revealed that increased serum cortisol binding by a saturable site, presumably CBG, was associated with CAH. Cortisol binding was significantly correlated with immunoassayable TBG, suggesting that in CAH, similar mechanisms may be responsible for increasing the serum concentrations of CBG and TBG. PMID- 2910095 TI - Serial lung function testing in patients treated with amiodarone: a prospective study. AB - PURPOSE: Amiodarone has proven to be effective in many cases of cardiac arrhythmias, refractory ventricular tachycardia, and ventricular fibrillation. Pulmonary toxicity is a possible side effect of the drug, with a reported incidence of 2 to 15 percent per year. To determine the effect of amiodarone on lung function, we prospectively studied serial lung function tests in a cohort of 91 patients with refractory cardiac arrhythmias treated with this agent. PATIENTS AND METHODS: Spirometry and carbon monoxide diffusing capacity (DLCO) were measured at zero, three, six, 12, 18, and 24 months, with a mean follow-up of 351 days. RESULTS: For the whole population taking a mean dose of amiodarone of 367 mg daily (range: 136 to 512 mg), there was no accelerated rate of decline in spirometric indices or DLCO. Analysis of lung function changes by multivariate analysis demonstrated that an accelerated decline in DLCO values occurred in elderly patients (p less than 0.05) but not in patients with pre-existing lung disease or cigarette smokers. In four patients (4.5 percent), clinical evidence of amiodarone pulmonary toxicity developed that was associated with a fall in DLCO of greater than 20 percent. All four patients recovered after the drug was stopped. Another 15 patients, without clinical evidence of pulmonary toxicity, had a sustained decline in DLCO of greater than 20 percent. These 15 patients remained asymptomatic over the next 11 months without interruption of therapy. A greater than 20 percent fall in DLCO was a sensitive test for clinically evident amiodarone pulmonary toxicity, but had a positive predictive value of only 21 percent. CONCLUSION: An isolated fall in DLCO, in the absence of clinical evidence of toxicity, does not necessitate stopping amiodarone. An unchanged DLCO value appears to be a reliable negative predictor of pulmonary toxicity. PMID- 2910096 TI - Elevation of plasma neuropeptide Y levels in congestive heart failure. AB - PURPOSE: Our objectives were to assess whether plasma neuropeptide Y (NPY) levels are elevated in patients with congestive heart failure (CHF) and whether or not NPY levels can serve as a reliable indicator of sympathetic activity in CHF. PATIENTS AND METHODS: Plasma levels of the sympathetic neurotransmitters norepinephrine and epinephrine and of the sympathetic co-transmitter NPY were measured in 17 patients with CHF and 14 healthy control subjects at rest and after maximal exercise. RESULTS: Under resting conditions, plasma NPY and norepinephrine levels were elevated in patients with CHF compared with control subjects (551 +/- 48 pg/ml versus 311 +/- 22 pg/ml, p less than or equal to 0.001 for NPY, and 306 +/- 73 pg/ml versus 124 +/- 22 pg/ml, p less than or equal to 0.02 for norepinephrine). Plasma NPY correlated better with plasma norepinephrine than with epinephrine, indicating its origin from sympathetic nerve terminals. Acute stimulation of sympathetic activity by dynamic exercise increased plasma norepinephrine levels in control subjects and patients with CHF, but did not significantly alter the mean plasma NPY value in the latter group. CONCLUSION: NPY may play a role in the pathophysiology of CHF. PMID- 2910097 TI - Non-Hodgkin's lymphoma in a population with or at risk for acquired immunodeficiency syndrome: indications for intensive chemotherapy. AB - PURPOSE: An increased risk of malignancies, including Kaposi's sarcoma and non Hodgkin's lymphoma, is found in patients infected with the human immunodeficiency virus type 1 (HIV-1). Treatment of such patients may be complicated by their underlying immunodeficiency, especially when aggressive regimens are used. Clinical presentation and treatment outcomes were assessed in 31 patients with non-Hodgkin's lymphoma who had or were at risk for infection with HIV-1 at a single community institution. PATIENTS AND METHODS: Lymphomas presented in advanced stages and involved extranodal sites. Twenty-six patients received therapy (two radiation, one surgery), and a total of 23 patients received chemotherapy. RESULTS: A 52 percent response rate was seen with the use of chemotherapy. A history of opportunistic infections, or Kaposi's sarcoma, or both impacted negatively on the ability to achieve a complete response. Sixty-four percent of the 11 patients who received an intensive chemotherapeutic regimen, MACOP-B (methotrexate, Adriamycin, cyclophosphamide, vincristine, prednisone, bleomycin) had complete remissions. Overall median survival for 23 patients who received chemotherapy was seven months. Patients achieving complete responses had a median survival of 20 months. CONCLUSION: Our results support intensive chemotherapy for patients with lymphoma and HIV-1 infection. PMID- 2910098 TI - Does the DNR order need life-sustaining intervention? Time for comprehensive advance directives. PMID- 2910099 TI - Hedge against extinction. PMID- 2910100 TI - Miss Alice and me. PMID- 2910101 TI - Surviving the stages of peer consultation. PMID- 2910102 TI - OSHA's new standard for hospitals' chemical hazards. PMID- 2910103 TI - Nurses improved their economic health in 1988; new attack on health benefits foreseen in 1989. PMID- 2910104 TI - Schools fear new shortage of faculty as salaries stall. PMID- 2910105 TI - Red blood cell transfusion risks. PMID- 2910106 TI - Nurse...or Scarlet Pimpernel? PMID- 2910107 TI - '89 salary update. PMID- 2910108 TI - Planning in advance for critical care. PMID- 2910109 TI - Great head nurses. PMID- 2910110 TI - Better breast milk for preemies? PMID- 2910111 TI - Managing nutrition problems in advanced cancer. PMID- 2910113 TI - Case for selective cholangiography. PMID- 2910112 TI - Who really manages hospitals? PMID- 2910114 TI - Development of an improved double-lumen biliary catheter for cholangiography. PMID- 2910115 TI - Does vasoactive intestinal polypeptide mediate the pathophysiology of bowel obstruction? AB - We hypothesized that bioactive peptides might be released into the portal circulation and mediate pathophysiologic alterations accompanying small bowel obstruction. We studied this question in a subacute canine small bowel obstruction model using 50 percent diameter occlusion. Control animals underwent sham laparotomy. Vasoactive intestinal peptide (VIP), peptide YY, and gastrin were measured in portal and systemic plasma by specific radioimmunoassays at 24 hour intervals as the obstruction progressed to completion over 5 days. All peptides in both groups demonstrated portal and peripheral gradients. In control dogs, peptide concentrations did not change postoperatively but VIP increased markedly in obstructed dogs, demonstrating a median portal level of 95 pmol/liter at 96 hours compared with 31.5 pmol/liter in control animals. These portal VIP levels are known to cause hypersecretion and splanchnic vasodilation in experimental models. The release of vasoactive compounds such as VIP may mediate local pathophysiology in human small bowel obstruction. A similar explanation of the systemic effects is consistent with the known cardiopulmonary bioactivity of VIP. PMID- 2910116 TI - Early evaluation and therapy for caustic esophageal injury. AB - Forty-one patients with caustic ingestion were reviewed. Eighty-three percent were children, all of whom suffered accidental injury. Liquid drain cleaner was the agent in 57 percent and was responsible for all esophageal burns. Symptoms and physical findings were unreliable in predicting the extent of injury. Endoscopy was performed in most patients within 36 hours of ingestion and accurately estimated the risk of subsequent esophageal stricture formation. Steroid administration had no influence on the development of strictures. Esophageal strictures developed in 22 percent of the patients. One-third were successfully managed by periodic dilation, whereas the remaining two-thirds required esophagectomy and reconstruction. Early endoscopic evaluation was the best means of assessing the degree of injury after caustic ingestion. Routine steroid administration had no apparent clinical benefit. PMID- 2910117 TI - Urgent biliary decompression after endoscopic retrograde cholangiopancreatography. AB - Acute cholangitis complicating diagnostic endoscopic retrograde cholangiopancreatography (ERCP) is potentially fatal. Among 323 consecutive patients with proved biliary obstruction, 21 (7 percent) developed acute cholangitis after examination. Four patients underwent emergency surgery for the control of sepsis with two deaths. Of the 21 parameters chosen for evaluation, malignant obstruction, fever (higher than 37.5 degrees C) within 72 hours before the procedure or when afebrile, and an increased aspartate transaminase level of 70 IU or more were the independent predictive factors identified by multivariate analysis. An increased temperature should be regarded as an absolute contraindication to examination unless followed by immediate ductal drainage. Since the risk of septic complications is minimal when none of the risk factors are present, routine urgent biliary decompression after ERCP is probably unnecessary for these selected patients. For patients with malignant obstruction or other risk factors, early elective surgical drainage is advisable. When surgery is not feasible, nonoperative drainage of the obstructed biliary system as a preventive measure might be considered. PMID- 2910118 TI - Impact of radiolabeled antibody imaging on management of colon cancer. AB - One hundred patients with known or suspected colorectal cancer were studied by radioimmunoconjugate scintigraphy prior to operation. Study subjects received murine monoclonal anticarcinoembryonic antigen labeled with indium 111 (Indacea). Sensitivity of imaging was 76 percent for primary tumors, 44 percent for hepatic metastases, 38 percent for extrahepatic abdominal metastases, and 78 percent for extraabdominal metastases. Seventeen of 46 patients (37 percent) with known or suspected hepatic metastases and no evidence of extrahepatic disease by conventional imaging methods had extrahepatic metastases at exploratory surgery. Nine of the 17 patients had disease accurately predicted by the Indacea scanning. The management of each of these nine patients was, or could have been, modified by the scan findings and unnecessary surgery eliminated. A number of patients without post-operative disease had an unexplained increase in plasma carcinoembryonic antigen level due to production of human antimouse antibody. The addition of excess mouse immunoglobulin to the plasma prior to assay blocked this artifactual increase. PMID- 2910119 TI - Failure of antioxidant therapy (polyethylene glycol-conjugated catalase) in acute pancreatitis. AB - Previous studies have demonstrated that intravenous catalase infusion protects against the formation of pancreatic edema in cerulein-induced acute pancreatitis; however, polyethylene glycol (PEG)-conjugated catalase given as a bolus was not protective. Using radiolabeled catalase and PEG-catalase in subtherapeutic tracer doses, the pancreas tissue distributions of each were determined in rats with and without pancreatitis. Rats with cerulein-induced pancreatitis developed tissue concentrations of catalase within the pancreas that were three times those of PEG catalase. The relatively low levels of PEG-catalase in the pancreas outside of the vascular compartment suggest that the failure to prevent edema formation may result from inability of PEG-catalase to reach extravascular sites of injury because of the large molecular size. PMID- 2910120 TI - Gastric restrictive operations for morbid obesity. AB - Gastric restrictive surgery has evolved over the past decade as the treatment of choice for morbid obesity. We reviewed our experience with 289 patients who underwent gastric surgery for morbid obesity. Comorbid diseases included respiratory insufficiency in 19 percent of the patients, hypertension in 36 percent, diabetes in 15 percent, arthritis in 30 percent, and heart disease in 6 percent. Operative mortality was 0. The follow-up rate was 93 percent. Overall mortality was 1 percent, with no death directly attributed to the operative procedure. Weight loss was studied over the 6-year study period. Four to 6 years postoperatively, overall weight loss was 50 to 64 percent of excess weight. The treatment failure rate 12 to 18 months postoperatively was 5 percent. The experience with gastric restrictive surgery in 12 centers involving 5,178 patients was reviewed and compared with our results. Overall operative and late mortality rates were quite similar to observed death rates for nonobese men and women between 25 and 64 years of age. These data suggest that gastric surgery for morbid obesity results in a significant reduction in health risk. PMID- 2910121 TI - Treatment of chronic alcoholic pancreatitis by pancreatic resection. AB - Forty-one patients with chronic pancreatitis caused by alcoholism were selected for resective surgery on the basis of clinical criteria and findings on pancreatography. Five patients had Whipple resections, 32 had 80 percent resections, and 7 had total pancreatectomies (3 previously had subtotal pancreatectomies). One perioperative and three late deaths accounted for the overall mortality of 10 percent. Complete freedom from pain on long-term follow up was achieved in all of the patients who had total pancreatectomy, in half of the patients who had 80 percent resection, and in only one of five patients who had Whipple resection. Diabetes occurred in only one patient after Whipple resection, in nearly half of the patients after 80 percent pancreatectomy, in a gradually accelerating manner, up to 5 years, and in all patients after total resection, where it was frequently complicated by recurrent alcoholism. Jaundice was a rare complication of disease progression in the overall treatment group; none of these patients presented with cholestasis preoperatively. Recurrent alcoholism was reported in 32 percent of the patients and contributed to two deaths. PMID- 2910122 TI - Pigment gallstone formation and altered ion transport. AB - Feeding corn and alfalfa to young prairie dogs resulted in formation of gallstones composed of 45 percent cholesterol, 30 percent bile pigments, and 25 percent calcium bilirubinate in half of the animals. This diet also resulted in increased gallbladder bile concentrations of calcium, phospholipids, and cholesterol. Although the cholesterol saturation index was significantly increased compared with control subjects, it remained less than 1. In addition to the changes in biliary lipid composition, the corn and alfalfa-fed animals had significantly decreased transepithelial potential difference and short-circuit current when compared with control animals. These are changes in gallbladder mucosal function similar to those that have been reported in humans with gallstones. This model may therefore prove to be of great value in studying the pathogenesis of noncholesterol gallstones. PMID- 2910123 TI - Down-regulation of pancreatic growth and gallbladder contractility by bile salts. AB - Luminal sequestration of bile salts with cholestyramine and the oral administration of bile salts represent current forms of therapy for some diseases. We have recently reported that secretion of these salts exerts negative feedback control on the release of cholecystokinin (CCK). The purpose of this study was to examine the effects of long-term alterations of luminal concentrations of bile salts on CCK target organs, the pancreas and gallbladder. The bile salt pool in adult guinea pigs was either enriched by feeding 0.5 percent sodium taurocholate or depleted by feeding 2 percent cholestyramine. Pancreatic growth, gallbladder contractility, the concentration of cholecystokinin receptors in the gallbladder muscle, and meal-stimulated plasma levels of cholecystokinin were significantly stimulated by feeding the bile salt sequestrant cholestyramine to guinea pigs. Administration of the bile salt taurocholate produced the opposite effects. Inhibition of CCK release by bile salts and up-regulation of CCK receptors by CCK may be the mechanisms responsible for the actions of bile salts on CCK target organs. PMID- 2910124 TI - Endogenous opiates in the mediation of early meal-induced jejunal absorption of water and electrolytes. AB - The purpose of this study was to investigate the role of endogenous opiates in mediating meal-stimulated jejunal absorption. Jejunal Thiry-Vella loops, 25 cm long, were studied in awake conditioned dogs, using luminal perfusion with carbon 14 polyethylene glycol. Fluxes of water, sodium, and chloride were calculated every 15 minutes over a 1-hour basal period, followed by a 3-hour experimental period. The animals were divided into four groups: control, naloxone, meal, and meal plus naloxone. In the control and naloxone groups, the fluxes did not change over the 4-hour observation period. Meal alone immediately stimulated the absorption of water and electrolytes in the Thiry-Vella loop (p less than 0.05). The addition of naloxone infusion to the meal stimulus resulted in significantly reduced absorption during the first hour after the meal (p less than 0.05). We concluded that endogenous opiates play a role in meal-stimulated jejunal absorption. PMID- 2910125 TI - Transduodenal sphincteroplasty and transampullary septotomy for primary sphincter of Oddi dysfunction. AB - We examined 29 patients without stone disease or pancreatic ductal ectasia who underwent transduodenal sphincteroplasty and transampullary septotomy for symptoms of biliary colic or pancreatitis. The combination of biliary symptoms and a fibrotic ampulla of Vater portends a favorable surgical outcome in virtually all such patients. Patients with pancreatitis did worse overall, perhaps due to the existence of unappreciated subclinical parenchymal disease not related to sphincter dysfunction. Although endoscopic retrograde cholangiography was sensitive in demonstrating abnormalities of the pancreaticobiliary system, its specificity as a predictor of good results was poor. It seems prudent to temper one's enthusiasm for sphincteroplasty in the patient with pancreatitis, whereas patients with biliary symptoms, the postcholecystectomy syndrome, or both will usually benefit significantly from this procedure. PMID- 2910126 TI - Roux-Y gastrectomy for chronic gastric atony. AB - The aim of this study was to determine the clinical outcome after Roux-Y gastrectomy for chronic gastric atony. Forty patients (11 men, 29 women; age 47 +/- 12 years) presented with severe chronic gastric atony: 32 patients had postvagotomy atony, 6 had idiopathic atony, and 2 had diabetic gastroparesis. The patients underwent either extensive subtotal or near-total gastrectomy and Roux-Y gastrojejunostomy. No early postoperative mortality occurred. Among the 39 patients followed for a mean of 32 months, 31 patients (79 percent) had fewer symptoms postoperatively than preoperatively, with 26 patients (66 percent) improving at least one Visick grade postoperatively and 22 patients (56 percent) going from grades III and IV preoperatively to grades I and II postoperatively. In contrast, 13 patients (33 percent) did not improve after operation. We concluded that extensive subtotal Roux-Y gastrectomy and near-total Roux-Y gastrectomy were safe procedures that led to improvement in two-thirds of the patients with chronic gastric atony; however, one-third of patients did not have improvement. PMID- 2910127 TI - Splanchnic neural regulation of pancreatic polypeptide release in the isolated perfused human pancreas. AB - The isolated perfused human pancreas was employed as a model in which electrical stimulation of the celiac mixed neural bundle was performed in the presence and absence of selective neural antagonists. Stimulation of the celiac neural bundle in the presence of hyperglycemia resulted in augmentation of pancreatic polypeptide release. Cholinergic stimulation appears to predominate, whereas beta adrenergic fibers stimulate pancreatic polypeptide-cell secretion, and alpha adrenergic fibers inhibit pancreatic polypeptide release. During euglycemia, both cholinergic stimulation and gastric inhibitory polypeptide infusion resulted in a marked release of pancreatic polypeptide. These stimulatory effects were additive, which suggests a linked hormonal and neural mechanism of pancreatic polypeptide release after a meal. In this in vitro human model, our data confirm that the splanchnic innervation of the pancreas has a potent regulatory role in pancreatic hormone release in man. PMID- 2910128 TI - The alkaline shift in gastric pH after cholecystectomy. AB - Previous studies using cholescintigraphy and measurement of bile salts in gastric juice have demonstrated that duodenogastric reflux is increased after cholecystectomy, a factor that may contribute to postoperative complaints in some patients. We studied 24-hour continuous gastric pH in healthy subjects, patients with cholelithiasis, and patients who had undergone cholecystectomy. Cholecystectomy decreased the percentage of time that gastric pH is below 2 and increased the time it is above 4 and 6. Furthermore, there was a greater increase in the more alkaline pH values in patients who were symptomatic than in those who were asymptomatic. The results demonstrated that cholecystectomy is associated with an alkaline shift in the 24-hour gastric pH profile that is most marked in symptomatic patients. This suggests that gastric alkaline episodes may be related to some postcholecystectomy symptoms. PMID- 2910129 TI - Effects of aspirin and acetic acid on intracellular pH in necturus gastric mucosa. AB - Intracellular microelectrode techniques were employed to examine the effects of luminal aspirin and acetic acid on intracellular pH and cell membrane potential in the surface epithelial cells of Necturus antrum. Antral mucosa was mounted in a modified Ussing chamber, and intracellular pH was determined from the difference between the potentials recorded by intracellular conventional and pH sensitive microelectrodes. Under neutral conditions (pH7), aspirin (5 mM) hyperpolarized (-7.5 +/- 1 mV, p less than 0.0001) and acetic acid (5 mM) depolarized (+4 +/- 0.08 mV, p less than 0.001) cell membrane potential. Neither agent had any significant effect on intracellular pH. Under acidic conditions (pH 4.5), aspirin (5 mM) reduced the intracellular pH from 6.99 +/- 0.03 to 6.87 +/- 0.04 (p less than 0.001) and depolarized cell membrane potential from -36.7 +/- 1.5 to -30.3 +/- 1.6 mV, p less than 0.001). Similarly, acetic acid (5 mM) acidified the cells (-0.20 +/- 0.02, p less than 0.001) and depolarized cell membrane potential (+9.6 +/- 1.9 mV, p less than 0.01). These changes suggest that, in the absence of luminal acid, small organic acids, such as aspirin and acetic acid, may have complex effects on the ionic conductances of the surface cell membranes without altering intracellular pH. In contrast, under acidic conditions, these agents increase the permeability of the apical cell membrane-to acid back-diffusion from the gastric lumen. PMID- 2910130 TI - Does delayed gastric emptying contribute to gastroesophageal reflux disease? AB - We studied 76 patients with symptoms of heartburn, regurgitation, or both and 38 asymptomatic control subjects by measuring the gastric emptying of technetium-99m labeled oatmeal. In addition, we performed 24-hour esophageal pH monitoring and manometric studies of the esophagus on all study participants. Endoscopy was performed on all patients. Patients with proved reflux on 24-hour pH monitoring, in comparison to those without reflux and the control subjects, had a shorter lower esophageal segment with a lower pressure and more esophagitis. Delayed gastric emptying occurred with equal frequency in patients with and without reflux. Esophageal reflux was not associated with delayed gastric emptying. Delayed emptying was associated with less esophagitis than found in those with normal gastric emptying, suggesting that the prolonged presence of food in the stomach may have a buffering effect on gastric acidity. We concluded that delayed emptying is not a major factor in the pathophysiology of gastro-esophageal reflux disease and that therapy aimed at speeding gastric emptying cannot be supported by our results. PMID- 2910131 TI - Supersaturation of canine gallbladder bile with calcium bilirubinate during formation of pigment gallstones. AB - Analogous to cholesterol gallstones forming in bile supersaturated with cholesterol, pigment gallstones may form in bile supersaturated with calcium bilirubinate. We tested this hypothesis in a dietary model of pigment gallstones. The concentration of ionized calcium (Ca++) and unconjugated bilirubin (UCB) was measured in 15 normal dogs and in 15 dogs with pigment gallstones induced by 6 weeks of a methionine-deficient diet. Although there was minimal change in the gallbladder's ability to acidify or concentrate bile, both [Ca++] and [UCB] markedly increased. These values were compared with equilibrium concentrations in model bile solutions. In all normal bile, the [UCB] was equal to or lower than the mean [UCB] concentration of model bile solutions with comparable [Ca++]. However, in all but one bile sample from dogs with pigment gallstones, the [UCB] exceeded this concentration and was therefore supersaturated with calcium bilirubinate. This supports the hypothesis that calcium bilirubinate precipitation is important in the formation and growth of pigment gallstones. PMID- 2910132 TI - Weight loss with vertical banded gastroplasty and Roux-Y gastric bypass for morbid obesity with selective versus random assignment. AB - In a previous study, Roux-Y gastric bypass was found to be significantly more effective than vertical banded gastroplasty for weight loss in morbid obesity, especially for patients addicted to sweets, probably as a result of dumping syndrome symptoms. This study evaluated the ability to selectively assign nonsweet eaters to vertical banded gastroplasty and sweet eaters to gastric bypass. Compared with random assignment, the percentage excess weight lost at 2 years improved significantly with both groups combined. In the vertical banded gastroplasty group, the percentage increased from 41 +/- 19 to 55 +/- 19 percent. With selective assignment, the percentage excess weight lost with gastric bypass was still better than that with vertical banded gastroplasty. Weight loss with gastric bypass was still superior to that of vertical banded gastroplasty but at the expense of more complications. Gastric bypass was ineffective in 19 percent of the super obese patients. A combined restrictive, malabsorptive procedure may be necessary in such persons. PMID- 2910133 TI - Dose-response relationships for edrophonium and neostigmine as antagonists of moderate and profound atracurium blockade. AB - To measure the ability of neostigmine and edrophonium to reverse moderate and profound atracurium blockade, dose-response relationships were established for these reversal agents given at 1% and 10% twitch height recovery. Eighty-five ASA I and II adult patients received atracurium, 0.4 mg/kg, during a thiopental nitrous oxide-enflurane anesthetic. Train-of-four stimulation was applied every 12 seconds, and the force of contraction of the adductor pollicis muscle was recorded. Edrophonium, 0.1, 0.2, 0.4, or 1 mg/kg; neostigmine, 0.005, 0.01, 0.02 or 0.05 mg/kg; or no reversal agent was given when there was either 1% or 10% recovery of the first twitch response. With profound blockade, the slope of the edrophonium dose-response relationship was significantly flatter (P less than 0.05) than that of neostigmine. The dose of neostigmine required to achieve 80% first twitch recovery (ED80) after 10 minutes was 0.013 +/- 0.003 mg/kg (mean +/- SEM) if given at 10% recovery, and 0.032 +/- 0.004 mg/kg if given at 1% recovery. The ED80 for edrophonium was 0.22 +/- 0.04 mg/kg and 1.14 +/- 0.33 mg/kg, respectively. These values corresponded to neostigmine:edrophonium potency ratios of 16.6 +/- 3.5 and 35.3 +/- 8.9 at 90% and 99% blockade respectively (P less than 0.006). We conclude that the relative potency of neostigmine is greater than that of edrophonium for antagonism of profound atracurium blockade. PMID- 2910134 TI - Thromboxane mediation of pulmonary hemodynamic responses after neutralization of heparin by protamine in pigs. AB - Protamine neutralization of heparin is often associated with severe hemodynamic side-effects, including pulmonary hypertension and systemic hypotension. Because prostanoids may be involved, the authors studied the role of arachidonic acid metabolites, especially thromboxane A2, in this process. During anesthesia with enflurane and fentanyl, four groups of pigs were studied: Group 1 (n = 10) received heparin (250 IU/kg), followed by protamine (100 mg) after 15 minutes to neutralize the heparin. The same protocol was used in group 2 (n = 11), except that the thromboxane A2 receptor antagonist BM 13.177 (10 mg/kg) was infused 5 minutes before the protamine. The protocol for group 1 was also used for group 3 (n = 7) except that these animals were pretreated with indomethacin (10 mg/kg). Animals in group 4 (n = 10) were given protamine only (100 mg). Pulmonary artery pressure and pulmonary vascular resistance increased significantly in group 1 after protamine neutralization of heparin. This was accompanied by significant increases in plasma concentrations of the cyclooxygenase products thromboxane B2, 6-keto-prostaglandin F1 alpha, and prostaglandin F2 alpha. Cyclooxygenase products increased to comparable degrees in group 2, but without hemodynamic effects. Leukocyte counts decreased comparably in both groups. Hemodynamic reactions, as well as changes in plasma prostanoid levels were absent in group 3, and group 4, but leukocyte counts were less affected in animals that received protamine alone. The results indicate that the hemodynamic side-effects of protamine are mediated by prostanoids and that thromboxane A2 release is the pivotal step, because side effects were effectively prevented by pretreatment with a thromboxane receptor antagonist.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2910135 TI - Paravertebral somatic nerve block: a clinical, radiographic, and computed tomographic study in chronic pain patients. AB - The spread of solution after a standardized paravertebral injection was studied to determine the precision and predictability of paravertebral spread. The spread of 5 ml of a solution of radiological contrast medium (sodium iothalamate) and local anesthetic mixture after 45 (34 thoracic, 11 lumbar) paravertebral injections was studied in 31 patients by radiography and computed tomography and correlated with the clinical effects. Spread confined to the paravertebral area occurred after only eight (18%) injections. Spread was epidural after 31 (70%) injections and exclusively so in 14 (31%) injections. Mean sensory loss was greater after epidural spread, but a wide range of sensation loss was observed with all patterns of spread. Intrapleural spread occurred after three injections, as did spread into the psoas muscle. In addition, measurements were made of 114 paravertebral spaces in 20 patients by means of computed tomography. Dimensional factors identified as possibly leading to complications of a paravertebral injection included narrow width of the thoracic transverse processes (mean, 3.18 cm; range, 2.1-4.2 cm) and the wide range in paravertebral dimensions. The distance from bony landmarks to pleura frequently fell outside the limits recommended by many standard texts. We conclude that the spread of a small volume of solution after paravertebral injection is imprecise and unpredictable. Neurolytic and diagnostic paravertebral injections performed without the aid of radiological imaging and contrast media should be regarded as hazardous and interpreted with extreme caution. PMID- 2910136 TI - Chronically administered progesterone decreases halothane requirements in rabbits. AB - The MAC for halothane is 25% lower in pregnant than that in nonpregnant ewes. The reason for this is uncertain, but changes in both steroidal and endogenous opiate have been implicated. This study was undertaken to assess the effect of exogenous progesterone on minimal alveolar concentrations (MAC) of halothane in ovariectomized rabbits. Minimal alveolar concentration of halothane was determined in 84 female rabbits, 37 intact (group A), 20 ovariectomized and injected with inert carrier peanut oil (group B), and 27 ovariectomized and injected with progesterone in peanut oil (group C). Minimal alveolar concentration in group A, 1.68 +/- 0.06% (mean +/- SEM), did not differ significantly from that in group B rabbits, 1.77 +/- 0.06%. However, MAC in progesterone-treated rabbits, 1.48 +/- 0.06%, was significantly lower than the MAC of the other two groups (P less than 0.01). Plasma progesterone concentrations in group A, B, and C were 5.28 +/- 0.62 ng/ml, 6.83 +/- 2.00 ng/ml, and 37.33 +/- 4.25 ng/ml, respectively. These results suggest that experimental treatment with progesterone can reduce the amount of halothane required to produce anesthesia and may explain the phenomenon of decreased need of inhalation anesthetic in human parturients. PMID- 2910137 TI - Unilateral Horner's syndrome associated with interpleural catheter injection of local anesthetic. PMID- 2910138 TI - Effect of epidural and intrathecal morphine on the length of hospital stay after cesarean section. PMID- 2910139 TI - Glossal pulse oximetry. PMID- 2910140 TI - Electroencephalographic burst suppression in elderly and young patients anesthetized with isoflurane. AB - The electroencephalograms of seven elderly (70-85 years) and seven younger patients (23-31 years) anesthetized with a concentration of isoflurane sufficient to produce burst suppression were studied. Anesthesia in these unpremedicated subjects was induced by inhalation of nitrous oxide, isoflurane, and oxygen. Tracheal intubation was facilitated with succinylcholine and the lungs were next ventilated with oxygen and isoflurane to produce an end-tidal concentration of 1.7%. Isoflurane concentration was determined by infrared analysis of expired gas collected from a Teflon catheter inserted through the endotracheal tube. After 25 minutes at steady state, the EEG was recorded for 5 minutes prior to surgical stimulation. Arterial blood pressure, temperature, and ventilation were maintained at normal values. In elderly patients the EEG had both a greater proportion of total time in electrical silence (76.0 +/- 10.8% vs 37.6 +/- 15.4%; P less than 0.01) and a greater number of isoelectric periods (19.7 +/- 8.1 vs 10.7 +/- 5.4; P less than 0.05). This demonstrates a discrete alteration with age in the central nervous system sensitivity to isoflurane. PMID- 2910141 TI - Subacute cor pulmonale due to tumor embolization to the lungs. AB - Six patients with subacute cor pulmonale due to tumor embolization to the lungs were reported from China. Five of the 6 patients suffered from progressive unrelenting dyspnea; 4 had completely normal cardiopulmonary findings on physical examination. Four of the 5 patients who had chest roentgenograms showed diffuse bilateral mottling of the lungs with no evidence of cardiomegaly. At autopsy right ventricular hypertrophy was present in all. The pathologic findings in the lungs consisted of multiple microscopic tumor emboli distributed diffusely in the pulmonary arterioles and/or perivascular lymphatics; the lumen of these vessels was obliterated with or without hyperplastic endarteritis. Although the outcome of this not uncommon clinicopathologic entity is generally fatal, early diagnosis followed by prompt effective therapy for the underlying primary neoplasm has been reported to prolong survival. PMID- 2910142 TI - Indirect, noninvasive evaluation of pressure wave transmission in essential hypertension. AB - Blood pressure, carotid-femoral and brachioradial pulse wave velocities were measured in 123 male subjects: 32 normal subjects and 91 age-matched patients with sustained essential hypertension. The ratio between brachioradial (BR) and carotid-femoral (CF) pulse wave velocities was used as a marker of pressure wave amplitude changes from the aorta to the brachial artery. The ratio was similar in normotensive and hypertensive subjects and decreased with age to the same extent in both populations. In older subjects, the decrease in the ratio indicated that the amplitude of pulse pressure was quite similar in the aorta and the brachial artery whether the subjects were normotensives or hypertensives. The study provided evidence that adaptive changes occur in the arterial (aortic) wall in hypertension, for the effects of age on pressure wave transmission are similar in normal subjects and hypertensive patients. Such findings may be of prime importance in understanding the brachial blood pressure readings of patients with hypertension. PMID- 2910143 TI - What do medical students know about in-hospital radiation hazards? AB - A questionnaire (eight multiple-choice questions) administered to 49 fourth-year medical students from the Limburg State University in the Netherlands shows that several misunderstandings, misconceptions, and erroneous beliefs exist in regard to in-hospital radiation hazards. The authors conclude that it is unlikely that ignorance about this subject is restricted to Dutch medical students. PMID- 2910144 TI - Effects of exercise training on biochemical and biomechanical properties of rat aorta. AB - The authors studied the effect of prolonged physical exercise on the mechanical properties of rat aorta in relation to the amounts and qualities of arterial connective tissue fibrous proteins. Twelve male rats were divided into two groups: 6 sedentary rats (S) and 6 training rats (T), which were forced to swim from nine weeks to twenty-five weeks of age. The ultimate tensile stress and the ultimate tensile extension ratio of ring specimens at the descending thoracic aorta were larger in T than in S (192.3 +/- 47.9 g/mm2, mean +/- SD, vs 147.8 +/- 26.0, p less than 0.05; 3.52 +/- 0.13 vs 3.18 +/- 0.27, p less than 0.05; respectively). The elasticity parameter, calculated by fitting stress-strain curves to exponential function in the stress level of 0-20 g/mm2, was lower in T than in S (1.79 +/- 0.15 vs 2.13 +/- 0.24, p less than 0.01). The contents of elastin (alkali-insoluble elastin preparation) and collagen were higher in T than in S (0.44 +/- 0.11 g/g dry aorta vs 0.30 +/- 0.06, p less than 0.05; 0.15 +/- 0.04 g/g dry aorta vs 0.11 +/- 0.04, NS, respectively). Although the aortic calcium content did not significantly change in the training rats (T 1.17 +/- 0.23 mg/g dry aorta, S 0.95 +/- 0.34), the content of calcium in elastin was lower in T than in S (1.75 +/- 0.51 mg/g dry elastin vs 2.63 +/- 1.00, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2910145 TI - Atrioventricular block in accidental hypothermia--a case report. AB - The finding of second-degree and high-grade atrioventricular block in a patient with severe accidental hypothermia is described. Additional findings included atrial fibrillation, severe sinus bradycardia, and prominent J (Osborn) waves. This case represents, to the authors' knowledge, the first report of advanced spontaneous AV block not induced by atrial pacing in severe accidental hypothermia. Reversal of the block, and other characteristic changes, suggest a relationship to low temperature. PMID- 2910146 TI - Microvasculopathy may precede idiopathic cerebral calcifications--case report. AB - Cerebral and cerebellar calcifications were discovered by computerized tomography (CT) in a man who presented with a dementing illness characterized by progressive memory loss, irritability, and dystonia. He had no known family. Magnetic resonance imaging showed areas of absent signal corresponding to the calcifications and areas of high-intensity signal on the T2-weighted images without counterpart on the CT. These are postulated to be static liquid pools secondary to endothelial membrane incompetence and leakage of plasma-derived fluid. PMID- 2910147 TI - Polymorphic ventricular tachycardia. AB - The case of a patient with torsade de pointes in the setting of congenital complete heart block is described. Lack of recognition of this polymorphic ventricular tachycardia resulted in therapy that potentiated the dysrhythmia. After correct recognition, and directed therapy, the patient responded appropriately. The clinical settings, recognition, and management options available for torsade de pointes are discussed to familiarize the emergency physician with this important and unique dysrhythmia. PMID- 2910148 TI - Who's stressing whom? PMID- 2910149 TI - Attending coverage revisited. PMID- 2910150 TI - Academic productivity or petulant work aversion? PMID- 2910151 TI - Digoxin-immune Fab fragments. PMID- 2910152 TI - Epinephrine dosage & arrest duration. PMID- 2910153 TI - Electromechanical dissociation. PMID- 2910154 TI - Sublingual nifedipine in the treatment of hypertensive crisis associated with monoamine oxidase inhibitors. PMID- 2910155 TI - Comparing the short-board technique. PMID- 2910156 TI - No adverse reaction. PMID- 2910157 TI - Massive pulmonary thromboembolism after antifibrinolytic therapy. PMID- 2910159 TI - Prevalence of in-flight medical emergencies on commercial airlines. AB - In-flight medical emergencies were evaluated among passengers arriving at Los Angeles International Airport (LAX) from October 1985 through March 1986. All emergency department, LAX first-aid station, and paramedic records were examined. There were 8,735,000 passenger arrivals at LAX during the study period; 260 passengers (0.003%) developed medical complaints in flight, and of these 260, 115 (44.2%) had symptoms that lasted for more than one hour. Only 20 (8%) had in flight physician assistance. One hundred thirty-seven (52.6%) passengers required only first-aid station treatment or signed out against medical advice, 123 (47.3%) were triaged to the ED, and 25 (9.6%) were admitted to the hospital. Seven passengers had fatal events while in flight. Most of the illnesses encountered did not require advanced medical treatment. We conclude that while in flight medical illnesses occur more frequently than believed by airlines, true emergencies are rare. The rarity of true in-flight medical emergencies coupled with low physician availability bring into question the benefit of any comprehensive medical kit on airliners. PMID- 2910158 TI - Financial analysis of an inner-city helicopter service: charges versus collections. AB - Trauma centers are now being perceived as financial burdens because of recent changes in trauma reimbursement for the Medicare Prospective Payment System population and the perception that collection rates are lower among trauma patients. We examined the demographic and clinical factors associated with the collection experience in a series of 114 trauma patients transferred by helicopter from the accident site to an inner-city trauma center. Factors affecting payment at 30, 60, 90, and 180 days included patient age, insurance class, and discharge status. While not as high as the collection rate for the facility as a whole, we found an average 71.2% collection rate for trauma patients at 180 days. As long as trauma reimbursement continues to be cost based for nonMedicare patients, collection rates remain an important consideration in determining the financial viability of trauma centers. PMID- 2910160 TI - The critically ill child in the pediatric emergency department. AB - A retrospective study of the charts of all critically ill patients visiting our pediatric emergency department over an 18-month period was conducted to determine age, diagnosis, time of presentation to the pediatric ED, Physiologic Stability Index (PSI) and Therapeutic Intervention Scoring System (TISS) score, and eventual outcome. Eighty percent of critically ill patients were less than 6 years old. Of these patients, 35% had neurological problems, 23% had lower airway disease, and 15% had upper airway obstruction. Forty-one percent of children presented during the day shift, 33% during the evening shift, and 26% at night. One hundred fifteen patients survived to discharge from the intensive care unit; eight patients died. A statistically significant difference in retrospectively assigned PSI scores in nonsurvivors (18.1 +/- 6.5) compared with those in survivors (5.2 +/- 3.5) was observed. There was also a statistically significant difference in retrospectively assigned TISS scores in nonsurvivors (32.4 +/- 3.2) compared with those in survivors (13.5 +/- 2.1). Implications for physicians involved in the emergency care of critically ill children and for designs of pediatric advanced life support programs are outlined. PMID- 2910161 TI - Attending coverage in academic emergency medicine: a national survey. AB - We surveyed the 66 accredited emergency medicine residency programs in the United States during 1986 on the issue of attending coverage. Responses were received from 411 residents and 288 faculty; this accounted for 42% of the residents and 56% of the faculty from the 56 responding programs. Seventy-three percent of emergency medicine residency programs had 24-hour attending coverage. According to residents, faculty from programs with 24-hour coverage spent a greater percentage of their shift doing primary patient care than faculty from programs without 24-hour coverage (35% vs 17%, respectively, P less than .0001), and a smaller percentage of their shift educating residents (21% vs 30%, respectively, P less than .0001). Ninety-five percent of faculty and 71% of residents thought that the quality of patient care was better when faculty were present in the ED (P less than .0001). Sixty-one percent of residents and 60% of faculty did not think that 24-hour attending coverage in academic emergency medicine should be mandated. The impact of night-time attending coverage in emergency medicine residency programs on patient care, resident education, and faculty development is unclear and minimally studied. PMID- 2910162 TI - Effect of crystalloid infusion on hematocrit and intravascular volume in healthy, nonbleeding subjects. AB - We evaluated the effect of IV crystalloid administration on hematocrit in 28 healthy, nonbleeding volunteers. Normal saline boluses of 10, 20, and 30 mL/kg were delivered at a mean rate of 115 +/- 4 mL/min, followed by a continuous infusion of either 1 or 5 mL/kg/hr. Hematocrit values determined immediately after bolus infusion declined from baseline a mean +/- SEM of 4.5 +/- 0.6 (P less than .001), 6.1 +/- 0.4 (P less than .001) and 6.3 +/- 0.6 points (P less than .001) in the 10, 20, and 30 mL/kg groups, respectively. Twenty minutes into the maintenance infusion, hematocrits had risen 1.5 +/- 0.8 (P = .03), 2.4 +/- 0.4 (P = .004) and 2.3 +/- 0.7 points (P = .005) when compared with post-bolus hematocrits in the 10, 20, and 30 mL/kg groups, respectively. These data show that in healthy, nonbleeding subjects, crystalloid infusion may cause significant changes in hematocrit. Calculations reveal that approximately 60% of infused saline, when delivered as a bolus, will diffuse from the intravascular space within 20 minutes of administration. PMID- 2910163 TI - Liquid automatic dishwashing detergents: a profile of toxicity. AB - The recent introduction of liquid automatic dishwashing detergents (LADDs) has resulted in numerous calls to poison information centers and, subsequently, a large number of referrals to emergency departments. As with their traditional granular counterparts, LADDs contain alkaline builders that contribute to the pH of these products. Exposure to granular automatic dishwashing detergents has been associated with caustic injury similar to the pathology produced by other alkaline corrosives. Do LADDs produce similar toxicity? There is no published information that profiles the toxic manifestations associated with exposure to LADDs. To determine their toxicity, all LADD exposures reported to a regional poison information center over a 12-month period were collected. One hundred ninety-two human exposure cases were reviewed. Pediatric patients accounted for 76% of the exposures; 76% were ingestions, 12% were dermal exposures, and 12% were ocular exposures. Seventy-nine percent of the patients were exposed to a full-strength product, and 21% contacted a dilute product or one that had already been through the dishwashing cycle. Of the patients who ingested a LADD, 91.1% remained asymptomatic, 8.2% had minor symptoms, and only one (0.7%) suffered moderate toxicity. In contrast, 91.3% of all patients who had an ocular exposure developed minor or moderate toxicity (73.9% vs 17.4%). Of dermal exposures, 69.6% were asymptomatic, and those with symptoms were the result of inappropriate use. Overall, 78.7% remained asymptomatic, 18.2% developed minor toxicity, and 3.1% developed moderate toxicity. Small oral and dermal exposures usually do not result in toxicity and do not necessitate referral to an ED. Ocular exposures are associated with a high incidence of at least minor toxicity and require ED evaluation. PMID- 2910164 TI - A new quantitative measurement for surgical needle ductility. AB - Because surgical needle ductility is such an important factor in the selection of surgical needles, a new curved needle ductility test instrument was devised to measure the ductility of needles from three commercial manufacturers. The superior ductility of needles made by one manufacturer was related to the specific alloy, stainless steel ASTM 45500, used in their production. The ASTM 45500 stainless steel has a significantly greater tensile and yield strength than the other stainless steel alloys, accounting for its superior ductility. PMID- 2910165 TI - Defibrillation safety in emergency helicopter transport. AB - Rotary aircraft play a growing role in the transport of critically ill patients who may require emergency treatment, including defibrillation, during transport. The close quarters and proximity of vital electronic equipment have generated concern among personnel carrying out defibrillation in the air. We address the chief safety issues in helicopter defibrillation by providing measurements of the transient leakage current resulting from contact with a paddle and tested in flight electronic interference and survey the defibrillation experience of helicopter programs. Our data show that airborne defibrillation is safe. A maximum of 1.5 mA of transient leakage current was measured from a standard battery-powered defibrillator, well within the accepted safety standard of 50 mA. In flight, there was no interference with the avionics or medical equipment, and adequate clearance was available for personnel. Of the helicopter programs surveyed, 69 (87%) had defibrillated in flight without incident. We conclude that defibrillation can be performed in the helicopter without hesitation whether on the ground or in the air, provided standard defibrillation precautions are observed. PMID- 2910166 TI - Postpartum abdominal pain. PMID- 2910167 TI - Psychological consequences of blunt head trauma and relation to other indices of severity of injury. AB - To investigate the relationship between APACHE II, Injury Severity Score (ISS), Glasgow Coma Score (GCS), and behavioral outcome, a group of 39 patients who had been admitted on an emergency basis with a traumatic head injury were selected from the Neuropsychology Registry for study. Except for subtle personality and cognitive changes, all of the patients were making good neurological recoveries. The Halstead-Reitan Neuropsychological Test Battery, which has been shown to be accurate in identifying brain-damaged patients, was used as the measure of outcome. The age of the patients ranged from 16 to 49 years (mean, 25.6; SD, 9.3). The patients' educational levels ranged from elementary school to college (mean, 11.6 years of education; SD, 1.5). Halstead Impairment Indexes (HII) ranged from 0.0 to 1.0 (mean, 0.6; SD, 0.26). APACHE II scores were calculated using the worst values, obtained during the first 24 hours. These scores ranged from 5 to 35 (mean, 16; SD, 7). APACHE II was found to not significantly correlate with HII (r = 0.21, P greater than .05). ISS was calculated for each patient and ranged from 5 to 70 (mean, 27; SD, 13). ISS was found to significantly correlate with HII (r = 0.38, P less than .01). GCS ranged from 3 to 15 (mean, 9.3; SD, 3.4). Of all the correlations, GCS was the most strongly correlated with outcome as measured by the HII (r = -0.44, P less than .01). Our data emphasize that head-injured patients have subtle cognitive dysfunction even when apparently recovering well and demonstrate the need for formal psychological evaluation in all patients with injury significant enough to warrant hospitalization. PMID- 2910168 TI - Fulminant bacterial meningitis without meningeal signs. AB - Common clinical practice relies on the absence of neck stiffness or other meningeal signs to rule out meningitis in the alert, healthy adult. The literature does not address this specifically but implies that meningeal signs are reliable and usually present in awake patients, except infants, the elderly, and the immunosuppressed. In the following three cases two adults and a 4-year old child, none of them immunosuppressed, presented with bacterial meningitis with no meningeal signs. In the first case, mental status was completely normal; in the second, there was only minor lethargy attributed to pain medication. In the third, lethargy was attributed to head trauma. In all three the diagnosis of meningitis was delayed up to 19 hours; lumbar puncture was performed while meningeal signs were still absent and cerebrospinal fluid analysis was grossly abnormal. All three patients had Streptococcus pneumoniae meningitis, and all three suffered massive brain damage within 24 hours of presentation and eventually died. Although the true incidence of absent meningeal signs in meningitis is unknown, the condition is rare. Clinicians cannot rely on the absence of neck stiffness to rule out meningitis, even in healthy and awake adults, and lumbar puncture should be performed whenever there is serious consideration of that diagnosis. PMID- 2910169 TI - Severe epinephrine-propranolol interaction. AB - A 53-year-old man presented to the emergency department with posterior pharyngeal edema. He had taken a long-acting propranolol product the previous evening that had been prescribed for migraine headaches. After administration of epinephrine subcutaneously in the ED, he developed a severe adverse reaction, characterized by profound hypertension and bradycardia. This potentially serious drug interaction is described, and relevant literature is reviewed. PMID- 2910170 TI - Nurses call for action by Congress. PMID- 2910171 TI - Change is operative word for 101st Congress. PMID- 2910172 TI - President's perspective. Ingredients of power: a government perspective. PMID- 2910173 TI - Nursing's agenda calls for accessible care. PMID- 2910174 TI - ANA is leader in AIDS advocacy and activism. PMID- 2910176 TI - Division of Governmental Affairs profiled. PMID- 2910175 TI - Nursing is political asset, say four RNs. PMID- 2910177 TI - SNAs educate RNs on passenger safety. PMID- 2910178 TI - Begin 1989 by planning for insurance needs. PMID- 2910179 TI - Bowen Commission issues report on shortage. PMID- 2910181 TI - Groups voice opposition to AMA plan for RCTs. PMID- 2910180 TI - Move to stop RCT loses in AMA House. PMID- 2910182 TI - Congress needs to hear nursing's views. PMID- 2910183 TI - Video nasopharyngoscopy: a comparison of fiberscopic, telescopic, and microscopic documentation. AB - Video nasopharyngoscopy is a most valuable method of documenting the anatomy and pathophysiology of the nasopharynx. Such a permanent record is useful for diagnosis, patient counselling, resident teaching, and the monitoring of therapy in nasopharyngeal disorders. To evaluate the various techniques for assessment of the nasopharynx, the authors have attempted to systematically compare flexible and rigid endoscopes and mirror examination during video recording. The pros and cons of 1) transnasal fiberscopic, 2) transnasal telescopic, 3) transoral telescopic, and 4) transoral microscopic mirror examination methods for video nasopharyngoscopy are discussed. PMID- 2910185 TI - Management of patients with glottic and subglottic stenosis resulting from thermal burns. AB - A series of 11 laryngeal burn patients is reviewed. Various methods of laryngeal burn management are detailed, including steroid usage, laser therapy, and reconstruction with local flaps, grafts, and stents. PMID- 2910184 TI - Utility of near-total laryngectomy for supraglottic, pharyngeal, base-of-tongue, and other cancers. AB - This report emphasizes the utility of the near-total laryngectomy for those patients in whom conventional conservation surgery is an option but may be oncologically or physiologically unsafe. The near-total operation can be offered for supraglottic cancer, pharyngeal cancer, and, more commonly, primary glottic cancer with cord fixation. Its application is described for patients who are candidates for conventional conservation surgery but are compromised physiologically by age or poor general health and for patients in whom tumor extent would not permit safe conventional conservation surgery. PMID- 2910186 TI - Advantages of the rotary door flap in laryngotracheal reconstruction: is skeletal support necessary? AB - Most attempts at laryngeal reconstruction have sought to reestablish skeletal support. Bone and cartilage grafts have been used for this purpose, but they have often failed to maintain position in the larynx and/or trachea following reconstruction, and they tend to be reabsorbed. The rotary door flap can provide an undelayed, one-stage epithelial resurfacing of the larynx and trachea while simultaneously restoring luminal support without the need for transfer of cartilage or bone. Luminal support for the trachea is provided by the bulk, turgor, and anterior traction of the intact sternohyoid muscle, which serves as the carrier for the rotated skin island. During inspiration the intact muscle, whose points of attachment are anterior to the plane of the larynx and trachea, contracts and tends to open the airway to provide dynamic luminal support. The need for internal stenting is minimized. The technique is described and experience in 20 patients is presented. PMID- 2910187 TI - Surgical correction of dysphonia due to bowing of the vocal cords. AB - This report reviews laryngoplastic techniques for correction of bowing of the vocal cords, with special consideration to the anatomic details of the anterior commissure. I present a new technique in which the glottic gap is closed by bilateral medialization. This technique may be superior to those described previously, since the correction achieved at the time of surgery is maintained by the placement of Silastic. PMID- 2910188 TI - Endoscopy and the KTP/532 laser for nasal sinus disease. AB - One hundred twenty-eight patients have undergone nasal/sinus operations using endoscopes and the KTP/532 laser. The pathologic processes have included turbinate dysfunction, nasal ethmoid polyps, hereditary hemorrhagic telangiectasia, granulomatous disease (sarcoid), nasal granulation secondary to cocaine abuse, and nasal papilloma. Early follow-up indicates rapid healing with minimal crusting, edema, scar formation, and complications and good resolution of disease. PMID- 2910189 TI - Laryngeal framework surgery in the management of spasmodic dysphonia. Preliminary report. AB - Spasmodic dysphonia continues to be a management problem for otolaryngologists. Selective lysis of the recurrent laryngeal nerve has been useful in the management of this disease. Reported long-term results, however, reveal that spasm recurs in approximately 40% to 50% of initially successful patients in spite of persistence of the unilateral vocal fold paralysis. Although some of these failure can be recaptured with subsequent laser surgery, the overall "cure" rate does not exceed 70%, even in the best hands. The contributions of Isshiki, LeJeune, and Tucker have demonstrated that tension in the vocal folds can be adjusted by laryngeal framework surgery. Experience with 16 patients suffering from adductor spasmodic dysphonia suggests that laryngeal framework surgery is useful in the management of this disorder. PMID- 2910190 TI - Computed tomography in patients with laryngeal carcinoma: a clinical perspective. AB - Among the various diagnostic modalities that have been recommended for preoperative assessment of the patient with laryngeal carcinoma is computed tomography. While good overall correlation between CT findings and operative findings has been noted, a significant number of false positives and false negatives have been found, particularly with regard to cartilage invasion and lymphadenopathy. We compared the findings of direct laryngoscopy, palpation of the neck, and CT with pathologic specimens in 29 patients who underwent surgery for carcinoma of the larynx. We found that CT scanning underestimated the extent of neoplastic involvement in over half the cases. With respect to cartilage invasion we determined a significant number of false-negative findings. Computed tomographic scanning was equivalent to palpation in predicting cervical metastasis. Our findings indicate that the role of CT scanning may be more limited than previously acknowledged, particularly in patients for whom nonconservation surgery is planned. PMID- 2910192 TI - Ventral cleft of the larynx in an adult. Case report. AB - Congenital clefts of the larynx are rare and usually found dorsally. This case report describes a patient with a partial anterior nonfunsion, or ventral cleft, of the thyroid cartilage. This was first noted on computed tomography of the larynx used for delineation of carcinoma and was confirmed by horizontal whole mount histologic sections of the resected larynx. The thyroid cartilage suggested arrested fusion of the laminae in the middle to late embryonic period. This patient had an adult form of this rarely reported anomaly and the first, to our knowledge, detected with CT scan. PMID- 2910191 TI - Squamous cell carcinoma of the thyroid: a diagnostic dilemma. AB - Four cases of primary squamous cell carcinoma of the thyroid gland are reported. Thorough evaluation confirmed these lesions to be of primary thyroid origin rather than from metastasis or direct invasion from contiguous structures. These cases illustrate the aggressive nature of the disease and the propensity for local and distant metastases. The clinicopathologic data presented here underscore the challenge in diagnosis and treatment of this rare entity. PMID- 2910193 TI - Voice restoration following laryngectomy: the role of primary versus secondary tracheoesophageal puncture. AB - A protocol was established at our institution to compare a series of primary and secondary tracheoesophageal punctures using the Singer-Blom voice prosthesis. Over a 24-month period, 20 primary and 18 secondary punctures were performed. Voice production, fluency of voice, and functional use were graded. Our data support the use of both primary and secondary voice restoration following laryngectomy. PMID- 2910194 TI - Detection of gastroesophageal reflux in the head and neck: the role of scintigraphy. AB - Patients with gastroesophageal reflux (GER) present to the head and neck specialist with a myriad of nonspecific complaints that may be manifestations of pharyngoesophageal or upper airway involvement. Numerous diagnostic tests for GER have been used in the past with varying success. In the present study, gastroesophageal scintigraphy using 99mtechnetium-sulfur colloid was used to evaluate 28 patients with head and neck manifestations of GER. The role of gastroesophageal scintigraphy as an accurate and noninvasive method of detecting GER is discussed in the context of other current diagnostic modalities. PMID- 2910195 TI - Newer techniques of laryngeal reinnervation. AB - We relate the experience obtained in the use of the right superior laryngeal nerve (motor branch)--cricothyroid muscle pedicle flap in dogs in an attempt to reinnervate the right posterior cricoarytenoid muscle (PCA). The right vocal cord was paralyzed by severance and removal of 2.5 cm of the right recurrent laryngeal nerve. Evaluation 6 months postoperatively revealed the vocal fold remobilization on the right side to have an average of about one half the mobility of the left, normal side. After the recurrent laryngeal and superior laryngeal nerves on the left were severed, the vocal cord mobility dropped to only about one fourth. This suggests that the dogs had contralateral reinnervation. Nevertheless, the right vocal cord mobility, driven only by the right superior laryngeal nerve, was enough to secure an adequate airway without the need for a tracheotomy. This experiment was statistically significant on comparison with a control group. Electromyographic studies as well as PCA histochemistry were performed. PMID- 2910196 TI - Posterior subglottic cyst. PMID- 2910197 TI - Practice of facial plastic surgery. PMID- 2910198 TI - Two cases of thyroid malignancy. PMID- 2910199 TI - The perpetual lessons of syphilis. PMID- 2910200 TI - Patchy alopecia in a young girl. Tinea capitis (most likely a Trichophyton tonsurans infection). PMID- 2910201 TI - Bowen's disease and internal malignant disease. PMID- 2910202 TI - Exacerbation of psoriasis. PMID- 2910203 TI - Scalp infestation with Phthirus pubis. PMID- 2910204 TI - Unilateral Muehrcke's lines following trauma. PMID- 2910205 TI - From the MMWR. Recommendations for diagnosing and treating syphilis in HIV infected patients. PMID- 2910206 TI - Pigmented guinea pig skin irradiated with Q-switched ruby laser pulses. Morphologic and histologic findings. AB - Q-switched ruby laser pulses cause selective damage to cutaneous pigmented cells. Repair of this selective damage has not been well described. Therefore, using epilated pigmented and albino guinea pig skin, we studied the acute injury and tissue repair caused by 40-ns, Q-switched ruby laser pulses. Gross observation and light and electron microscopy were performed. No specific changes were evident in the albino guinea pigs. In pigmented animals, with radiant exposures of 0.4 J/cm2 or greater, white spots confined to the 2.5-mm exposure sites developed immediately and faded over 20 minutes. Delayed depigmentation occurred at seven to ten days, followed by full repigmentation by four to eight weeks. Regrowing hairs in sites irradiated at and above 0.4 J/cm2 remained white for at least four months. Histologically, vacuolation of pigment-laden cells was seen immediately in the epidermis and the follicular epithelium at exposures of 0.3 J/cm2 and greater. Melanosomal disruption was seen immediately by electron microscopy at and above 0.3 J/cm2. Over the next seven days, epidermal necrosis was followed by regeneration of a depigmented epidermis. By four months, melanosomes and melanin pigmentation had returned; however, hair follicles remained depigmented and devoid of melanocytes. This study demonstrates that selective melanosomal disruption caused by Q-switched ruby laser pulses leads to transient cutaneous depigmentation and persistent follicular depigmentation. Potential exists for selective treatment of pigmented epidermal and dermal lesions with this modality. PMID- 2910207 TI - Anaphylactic symptoms due to chlorhexidine gluconate. AB - Six patients who developed urticaria, dyspnea, and anaphylactic shock due to topical application of chlorhexidine gluconate solution are described. Chlorhexidine gluconate was confirmed as the causative agent of type I hypersensitivity by intradermal, scratch, and epicutaneous tests. To prevent life threatening adverse reactions, it seems important to use chlorhexidine gluconate on wound surfaces at a concentration of 0.05%, as recommended by the manufacturer; chlorhexidine gluconate may not be suitable for application to mucous membranes. PMID- 2910208 TI - The mineralization of elastic fibers and alterations of extracellular matrix in pseudoxanthoma elasticum. Ultrastructure, immunocytochemistry, and X-ray analysis. AB - Histologic paraffin sections of pseudoxanthoma elasticum (PXE)-involved skin of forearm and axilla were used for histochemistry and immunohistochemical and analytical electron microscopy to study the progressive mineralization in the dermis of patients with PXE. The von Kossa technique identified mineral deposits throughout the reticular PXE dermis. X-ray analysis revealed patterns of calcium and phosphorus deposition in the von Kossa-positive areas, and the immunohistochemical staining using monoclonal antibodies identified increased chondroitin-6-sulfate in these areas when compared with normal skin. Scanning transmission electron microscopy observation combined with X-ray dot mapping show calcium and phosphorus to be codistributed within the mineralized area. This study confirms by new methods the increase in chondroitin-6-sulfate, alterations in elastin and collagen, and a high calcium and phosphorus elemental distribution matching the mineralized area in the PXE dermis. PMID- 2910209 TI - Failure of erythromycin to cure secondary syphilis in a patient infected with the human immunodeficiency virus. AB - The case presented here involves a 32-year-old homosexual man with human immunodeficiency virus seropositivity and secondary syphilis. Because of possible penicillin allergy, he was initially treated with erythromycin base by mouth. During four weeks of therapy, his cutaneous lesions worsened as did his systemic symptoms. Following desensitization and parenteral penicillin therapy, his cutaneous lesions and symptoms rapidly resolved. His VDRL titer fell appropriately. PMID- 2910210 TI - Post-traumatic parotid fistulae and sialoceles. A prospective study of conservative management in 51 cases. AB - The management of parotid sialoceles and fistulae have been unsatisfactory in the past, and numerous methods of treatment with varying success and morbidity have been described. The present prospective study reports results of conservative therapy in 51 patients over a 3-year period. In 50 patients, the injury healed upon conservative management. During the early phase of the study, a limited conservative regimen through which the patients received nothing orally for 5 days only was used. During the latter part of the study, patients were administered nothing orally until complete healing of the injury. In terms of the time it took for healing of the injury, the differences of the two regimens (24 +/- 4 vs. 9.4 +/- 0.9 days) was highly significant (p less than 0.001). The response to conservative management depended on the severity of injury as demonstrated by sialography. Injury to minor intraparotid ducts (G1) healed in significantly less time compared with that to a major intraparotid duct (G2) or ductal injuries (p less than 0.001). There was no difference between the healing of G2 injury (10.3 +/- 1.8 days) and partial ductal transections (10.5 +/- 2.2 days) (p greater than 0.05). There was a significantly greater delay in healing with complete duct transections (21.5 +/- 3.7 days) compared with partial duct transections and G2 injuries (10.2 +/- 2.1 days) (p less than 0.01). There was no difference in the mean period for healing between salivary fistulae and sialoceles (p greater than 0.05). It is concluded that a new classification of parotid fistulae based on sialographic findings has prognostic and therapeutic value. Furthermore, the excellent results achieved with conservative therapy in this study suggest that it may be the initial treatment of choice for parotid fistulae. PMID- 2910211 TI - Chronic TNF infusion causes anorexia but not accelerated nitrogen loss. AB - It has been proposed that many of the physiologic and metabolic changes that occur during critical illness and malignancy are mediated by the cytokine tumor necrosis factor alpha/cachectin (TNF). To test this hypothesis, a study of the metabolic responses that occurred during 5 days of continuous intravenous (I.V.) infusion of TNF both in rats and tumor-bearing humans was conducted. TNF administration was associated with anorexia, fluid retention, acute phase responses, and negative nitrogen balance. In both species, changes in nitrogen balance were related to the onset of anorexia and not to the development of hypermetabolism and accelerated net tissue breakdown. TNF may represent the primary afferent stimulus inducing many of the metabolic changes that occur during critical illness, but it is not solely responsible for the accelerated net proteolysis that occurs in these patients. PMID- 2910212 TI - Pancreatic lymphoma. Is surgery mandatory for diagnosis or treatment? AB - From 1982 to 1986, nine patients with non-Hodgkin's lymphoma primarily involving the pancreas were managed at the Johns Hopkins Medical Institutions. This group of nine patients represents 2.2% of patients with non-Hodgkin's lymphoma (nine of 402) and 4.9% of all patients presenting with pancreatic malignancies (nine of 182) at the Johns Hopkins Medical Institutions during this period. Computed tomography (CT) scan findings of a large pancreatic mass (6 cm) with extrapancreatic extension and significant retroperitoneal lymph node enlargement suggested lymphoma. Diagnosis was established by radiographically-guided needle biopsy in four patients, by laparotomy in four, and by peripheral lymph node biopsy in one. In five jaundiced patients, initial chemotherapy with the nonhepatotoxic agents cyclophosphamide and prednisone resulted in marked tumor regression, allowing for early resolution of jaundice and subsequent addition of more aggressive adriamycin containing combination chemotherapy. Overall, complete remission has occurred in six of nine patients, with a median survival of 24 months (range 4-69 months). It is concluded from this experience that the majority of patients with pancreatic lymphoma can be managed without surgery. Excellent control of symptoms, including jaundice, as well as long-term remission, can be obtained with chemotherapy alone. The only role for surgery in this setting may be to aid in establishing the diagnosis when percutaneous biopsy is nondiagnostic. PMID- 2910213 TI - Pancreatography after recovery from massive pancreatic necrosis. AB - Massive retroperitoneal necrosis may follow life-threatening acute pancreatitis. At delayed operation, the surgeon may not be able to delineate dead pancreas from dead adipose tissue. The question arises: has "gloved hand" debridement resulted in pancreatectomy? The histologists report only "necrotic debris, of uncertain origin." To obtain objective data, pancreatography was performed in 13 patients, 10 weeks to 23 months after onset of massive pancreatic necrosis. Each patient had required delayed laparotomy for debridement and external drainage at some earlier stage of their illness. Pancreatography was correlated with the clinical assessment of diabetes and steatorrhea. Except in specific cases involving internal fistulae, pancreatography has not been previously reported in such patients. The results demonstrate that the main pancreatic duct usually maintained its normal length and configuration. Necrosis or stricture of the main duct, if it occurred, was more likely to be followed by diabetes. Steatorrhea was clinically detected in a single patient only. The necrotic tissue, up to several kilograms in wet weight, is largely dead adipose tissue. The pancreas, especially its head, is resistant to necrosis, much more resistant than is the retroperitoneal fat. PMID- 2910214 TI - The need for definitive therapy in the management of perforated gastric ulcers. Review of 202 cases. AB - A retrospective study of 202 patients who presented to three Louisiana hospitals with perforated gastric ulcers was performed. Patients were treated surgically, medically, or were not treated. Only those patients with gastric ulcers were included in the study, not those with "channel ulcers" or peptic ulcers. The mortality rate of the 185 patients who were treated with operation was 18%. Of those patients treated nonoperatively, the mortality was 95% (one survivor). There was a definite difference in mortality among those patients treated with definitive operative procedures (11.3%) versus those patients treated with nondefinitive surgery (22.9%). This difference was consistent even in the presence of purulent exudate in the abdominal cavity and among those patients presenting in shock. The mortality among those patients who presented with a initial blood pressure of 90 mmHg or less were defined as being in shock, and the mortality in this subgroup was 52.8%. The mortality among those patients who had purulent fluid within the abdominal cavity was about the same, regardless of type of surgical procedure. The patients who underwent nondefinitive procedures required subsequent operative treatment in 25.7% of cases. Also noted was the lack of correlation between symptoms of ulcer disease and perforation. Those patients treated with definitive surgery (57%) and those treated with nondefinitive surgery (41%) reported no symptoms consistent with ulcer disease before operation. PMID- 2910215 TI - Plasma-amino acid profiles in sepsis and stress. AB - Sepsis has been associated with specific plasma amino acid patterns. Sixty-five patients were prospectively investigated as to whether these patterns are indeed sepsis specific, or specific for metabolic stress without concomitant sepsis, or associated with the presence of organ failure. Virtually all aminoacid levels were decreased by 10-30% (p less than 0.05), whereas cystine and phenylalanine were significantly elevated. These changes were more pronounced in severe sepsis. Organ failure was not associated with significantly altered amino acid profiles. No differences were found between sepsis and stress without signs of sepsis. In addition, imminent death was not associated with aberrant amino acid profiles. We conclude that sepsis and metabolic stress are associated with changes in plasma amino acid profiles, but that such changes are aspecific and therefore poor indicators of disease severity. PMID- 2910216 TI - A phase II study of the efficacy of diamminedichloroplatinum (cisplatin) for the control of locally recurrent and intransit malignant melanoma of the extremities using tourniquet outflow-occlusion techniques. AB - A phase II trial was conducted with 15 patients (mean age of 65.7 years) with locally recurrent or intransit melanoma of the extremities. After total outflow occlusion with pneumatic tourniquet, the cell-cycle nonspecific anti-neoplastic agent cis-diamminedicholoroplatinum (CDDP) was infused intra-arterially in a mean dose of 26.7 mg/m2 per infusion (2.6 infusions per patient). The aim of this study was to determine the efficacy of CDDP infusion for control of intransit and recurrent melanoma of the extremities. Three to four weeks postinfusion, all visible residual disease was resected. Partial remissions were observed in ten patients (67%); five patients achieved stable disease status. No patient had complete regression of disease. At an average follow-up interval of 18.3 months (range 4-44 months), the mean local/regional disease-free survival was 14.8 months. Eighty per cent of patients (twelve of 15) had local/regional control of disease at an average follow-up of 14.8 months after CDDP infusion and surgical resection. Of five melanoma-related deaths, three patients had had no local/regional recurrence at the time of their demise. Three compartment syndromes resulted as a complication of the infusional therapy and occurred within 1-3 days of the treatment. In vitro growth of melanoma from lymph nodes draining the infused area was seen in all subjects studied. Outgrowth from tumor within the tourniquet infusion area was observed in two patients, both of whom experienced recurrences clinically at 24-months' postinfusion. Pharmacokinetic data of total CDDP concentrations from tissue and blood (n = 4) were available from pretreatment to 1 hour post-therapy. Biopsy data from patients pre- and post treatment suggest substantial tumor uptake of CDDP as compared to local or distal normal skin, with minimal CDDP loss to the systemic circulation. Pharmacologic and clinical data of this phase II trial suggest that intraarterial infusion with tourniquet outflow-occlusion augments tumor tissue levels of CDDP within the infused extremity and enhances local control of high-risk and intransit disease. PMID- 2910217 TI - Predicting mortality based on body composition analysis. AB - The role of the Nae/Ke ratio (the ratio of exchangeable sodium to exchangeable potassium) was examined as a nutritional marker in surgical patients in relation to anthropometrical and biochemical indexes by its ability to identify patients at risk for mortality after hospitalization. In 73 patients with sepsis and malnutrition (Training Group, Madrid) the following were determined: percentage of recent weight loss, triceps skin fold, midarm muscle circumference, serum albumin, serum transferrin, delayed hypersensitivity skin test response, total lymphocytes, and Nae/Ke ratio by multiple isotope dilution. The predictive power of Nae/Ke ratio was so strong (F = 105.1; p less than 0.00001) that it displaced anthropometric, biochemical, and immunologic variables from the linear equation derived from stepwise discriminant analysis using hospital mortality as the dependent variable. A theoretical curve of expected deaths was developed, based on an equation obtained by logistic regression analysis: Pr/death/ = 1/(1 + e[11.8-5.2 Nae/Ke]). Pre- and post-test probabilities on that curve allowed us to determine two cut-off values, Nae/Ke ratios of 1.5 and 2.5, which were markers for nonrisk and mortality, respectively. The model was tested in a heterogeneous data base of surgical patients (n = 417) in another hospital (Validation Group, Montreal). For patients exhibiting an abnormal Nae/Ke ratio (greater than 1.2) and a greater than 10% of probability of death, 54 deaths were expected and 53 observed (X2 = 1.8 NS). Two tests confirmed the basic agreement between the model and its performance, a G statistic of -0.704 and the area beneath the "receiver operating-characteristic" (ROC) curve (Az = 0.904 + 0.0516 for the Madrid group vs. Az = 0.915 + 0.0349 for the Montreal group, NS). It was concluded from this analysis that, compared with the usual anthropometric measurements, the Nae/Ke ratio, if available, is the best method for identifying malnourished patients at risk of dying. PMID- 2910218 TI - Problems associated with the EEA stapling technique for esophagojejunostomy after total gastrectomy. AB - Since November 1980, the EEA stapling device has been used to create an end-to side esophagojejunostomy in 238 patients who underwent total gastrectomy. Failures in the stapling technique were divided into two groups: immediate and delayed. Immediate failures were observed and corrected at the time of surgery. In ten cases, the muscular layer of the esophagus was disrupted, and in three the mucosal layer of the jejunum was disrupted. There were 18 delayed complications: eight cases of anastomotic leakage (3.4%), and ten of stenosis (4.2%). The leakage in one case was classified as major, and those in the other seven as minor. Of the ten stenosis cases, there were five of membranous stricture, four of granular stricture, and one of narrowing after major leakage healing. Only this last case required further surgical treatment. The other nine were successfully dilated either endoscopically or by bougienage. PMID- 2910219 TI - Lithium treatment and serotoninergic function. Neuroendocrine and behavioral responses to intravenous tryptophan in affective disorder. AB - Evidence suggests that lithium treatment alters serotoninergic (5-HT) function in laboratory animals and humans. Since 5-HT function may be abnormal in patients with affective disorders, we studied 23 such patients by measuring responses to intravenous infusion of the 5-HT precursor tryptophan before and during short term (less than one week) or long-term (greater than three weeks) lithium treatment. The prolactin response to tryptophan was significantly enhanced after short-term lithium treatment; long-term lithium treatment had no effect. Other studies have shown that the prolactin response to tryptophan is also enhanced after long-term tricyclic antidepressant treatment in depressed patients and after short- and long-term lithium treatment in healthy subjects. The present findings suggest that lithium treatment enhances 5-HT function, but that homeostatic responses of the 5-HT system to long-term lithium treatment may differ in patients with affective disorder and healthy subjects. PMID- 2910220 TI - Clomipramine in obsessive-compulsive disorder. Further evidence for a serotonergic mechanism of action. AB - Data from several previous studies link clomipramine's potent serotonergic effects to its clinical efficacy in reducing the symptoms of obsessive-compulsive disorder (OCD). To investigate this relationship further, we administered the serotonin (5-HT) receptor antagonist, metergoline, and placebo to ten patients with OCD in a crossover study carried out under double-blind, random-assignment conditions. In a previous study of untreated patients with OCD, we found no differences in the behavioral response to single-dose administration of metergoline or placebo. In the present study, patients with OCD receiving clomipramine hydrochloride on a long-term basis (with an average 40% lessening in OC symptoms) responded to a four-day period of administration of metergoline with significantly greater self- and observer-rated anxiety compared with the four-day placebo period. Obsessive-compulsive symptoms also tended to be greater during the metergoline phase, with significant drug-time interactions for both OC symptoms and anxiety peaking on day 4 of the metergoline phase. As anticipated, metergoline lowered plasma prolactin concentrations (providing evidence of physiologically significant 5-HT antagonism) but did not alter plasma clomipramine concentrations. These data further support the hypothesis that clomipramine's therapeutic behavioral effects in OCD are mediated via serotonergic mechanisms. PMID- 2910221 TI - Eating behavior of women with bulimia. AB - To obtain objective information about binge- and non-binge-eating behavior, 12 women with bulimia and ten women without eating problems (controls) were asked to eat four meals in a structured laboratory setting, on separate nonconsecutive days. The same instructions were given to both groups. On two days, they were asked to eat a normal amount, and on two days, they were asked to eat as much as they could, ie, to binge. For each type of instruction, they were given a single- and a multiple-course meal. The patients ate significantly more than the controls when asked to binge, both on the multiple-course meals that they rated as typical of binges and on the single-course meals. When they were asked to eat normally, there was no significant difference in intake between patients and controls on either single- or multiple-course meals. After all meals, hunger ratings of patients were significantly higher than hunger ratings of controls. There was also a significant positive correlation between intakes of single- and multiple course binge meals and an inverse correlation between intake of multiple-course binge meals in bulimic patients and their rating of how well they controlled their eating. Thus, a structured laboratory eating situation can be used to reveal differences between bulimic and normal individuals and has the potential for assessing clinical status and exploring mechanisms responsible for binge eating. PMID- 2910222 TI - Changes in melatonin levels but not cortisol levels are associated with depression in patients with eating disorders. AB - Disturbances were studied in the nocturnal circadian pattern of serum melatonin and plasma cortisol levels in 33 female patients with an eating disorder (anorexia nervosa, n = 11; bulimia nervosa, n = 12; or both, n = 10) and in ten female control subjects of comparable age. Blood samples were obtained hourly from 8 PM to 6 AM under controlled darkness. Serum melatonin levels in all patient groups were initially similar to those of control subjects. When patients were divided according to depression status, those with concurrent major depression had significantly lower nocturnal melatonin values than the nondepressed group. Weight did not appear to influence melatonin levels. In contrast, all patient groups had significantly higher nocturnal levels of plasma cortisol than control subjects, and neither weight nor depression separated patient groups on profiles of plasma cortisol. PMID- 2910223 TI - State of hepatitis B virus DNA in hepatocytes of patients with noncarcinomatous liver disease. Its special relationship with necroinflammatory activity and the stage of disease. AB - By Southern blot hybridization, the state of hepatitis B virus (HBV) in the liver was investigated by utilizing needle biopsy specimens of 59 patients with hepatitis B surface antigen-positive noncarcinomatous liver disease. The tissue HBV DNA revealed a replicative form in 23 patients with chronic active hepatitis (48%) and an integrated form in 23 (48%) of these 48 patients. A liver with a replicative form was more frequently associated with hepatitis Be antigen (HBeAg), serum HBV DNA, and expression of hepatitis B core antigen than one without it. Integration of HBV DNA was more common in the anti-hepatitis Be phase or in the absence of necroinflammatory activity, and its frequency of occurrence roughly paralleled progression of liver disease: early, 21%; advanced, 56%; and cirrhotic stage, 61%. PMID- 2910224 TI - Eosinophils in skin lesions of erythema multiforme. AB - To investigate the controversy regarding the presence of eosinophils in skin lesions of erythema multiforme, we undertook a retrospective clinicopathologic study of 19 recent cases that fulfilled clinical and histopathologic criteria for the disease. At least a few eosinophils were observed in 13 of 19 cases, and in four cases there were more than three per high-power field, qualifying as "tissue eosinophilia." Immunofluorescence studies in three cases with eosinophils failed to show the linear basement membrane zone fluorescence characteristic of bullous pemphigoid. Giemsa stains revealed that mast cells were present in lesions both with and without eosinophils. The only clinical features that distinguished patients with tissue eosinophilia from those without were an older age of incidence and a longer duration of disease prior to biopsy. Drugs were implicated as a causative factor in some patients both with and without eosinophils, but all four patients with tissue eosinophilia were believed to have drug-induced disease. We conclude that eosinophils do occur in skin lesions of erythema multiforme and are occasionally numerous. PMID- 2910225 TI - Juvenile granulosa cell tumors of the ovary. AB - The clinical and pathologic features of 13 cases of juvenile granulosa cell tumor were studied. Patients' ages ranged from 6 months to 56 years (median age, 17 years). Only one patient was postmenopausal. Three premenarchal patients had isosexual development. Five of seven postmenarchal patients had menstrual abnormalities, and two patients demonstrated virilization. Ascites was present in two patients. All patients had unilateral stage I tumors, ranging from 2.5 to 24.5 cm in greatest dimension (mean greatest dimension, 12.2 cm). Characteristic histologic features included nodular architecture, follicle formation, abundant interstitial and intrafollicular acid mucopolysaccharide-rich fluid, irregular microcysts, individual cell necrosis, and high mitotic activity (mean activity, 11 mitotic figures per ten high-power fields). The interstitial mucinous fluid consisted predominantly of hyaluronic acid. Immunohistochemical staining in five cases showed prominent positivity for vimentin (four cases), isolated cytokeratin AE1/3-positive cells (two cases), and nonreactivity for carcinoembryonic antigen and milk fat globule-2. Ultrastructurally, epithelial cells that resembled granulosa cells of the nonneoplastic preovulatory follicle and occasional cells with steroidogenic organelles were also found. Follow-up of ten patients revealed no tumor recurrences from six months to 33 years (mean, 9.5 years) after operation. PMID- 2910226 TI - Extra-adrenal myelolipoma. AB - Extra-adrenal myelolipomas are rarely reported lesions, with only 18 cases found in the world literature. We report a series of three cases, all occurring in women in an age range of 68 to 83 years (mean, 77 years). One patient presented with a pelvic mass while the other two cases were incidental findings at autopsy. All lesions were presacral in location, encapsulated, and not attached to adjacent structures. Sizes ranged from 6 to 12 cm in greatest dimension and from 72 to 330 g. Color was a variegated yellow to red-brown. Microscopically, all were composed of mature fat and focal collections of normal hematopoietic elements. The nature of these lesions is not known but most authors favor a choristomatous origin. They must be distinguished from extramedullary hematopoietic tumors seen in patients with severe anemias, myeloproliferative disorders, and skeletal disease. PMID- 2910227 TI - Pseudoepitheliomatous hyperplasia in Spitz nevi. A possible source of confusion with squamous cell carcinoma. AB - The presence of epithelial hyperplasia in Spitz nevi has been recognized almost from the time of Spitz's first description of the distinctive lesion that bears her name. However, the fact that this hyperplasia can acquire pseudoepitheliomatous features and thus lead to a mistaken diagnosis of squamous cell carcinoma is not widely appreciated. This report describes six examples of this phenomenon. PMID- 2910228 TI - Clinical diagnosis is not a source of bias in selection for necropsy. AB - Recent reports have suggested a minimal difference in demographics between hospital deaths undergoing necropsy and those that do not. In order to assess whether the clinical diagnosis at death influenced the decision to request necropsy in deaths occurring in the hospital, a 10% sample of all adult necropsies at the University of Kansas Medical Center (Kansas City) from 1962 through 1981 was obtained. These patients (cases) were matched by age, race, sex, and date of death to hospital deaths not undergoing necropsy (controls). The charts were reviewed, and the primary diagnosis at death was ascertained and categorized into one of the 14 categories of the International Classification of Diseases. There were 412 case-control pairs, with 237 men and 175 women in each group. Most patients were classified under the headings Circulatory (142 cases vs 140 controls) and Neoplasm (143 cases vs 148 controls), followed by Respiratory (21 cases vs 33 controls) and Digestive (44 cases vs 28 controls). Overall, no statistically significant differences were observed between cases and controls. There were no gender-specific differences in all but two of the categories. In men, the controls had more patients classified under the heading injury (19 vs seven). In women, the control group had more patients classified under the heading Respiratory (14 vs four). Because of multiple comparisons, these findings could have occurred by chance. These data suggest that the primary diagnosis at death is not a source of bias in the selection for necropsy. Consequently, necropsy-selection bias, if it exists, may be due to other factors, such as the complexity of the patient's clinical course. PMID- 2910230 TI - Primary choriocarcinoma of the lung in a man. AB - A case of nongestational, extragonadal choriocarcinoma in a middle-aged man is described. Autopsy examination confirmed that the tumor originated in the lung. The trophoblastic origin of the tumor was documented by immunoperoxidase staining for human chorionic gonadotropin. PMID- 2910229 TI - Lectin histochemistry in adrenocortical hyperplasia and neoplasms with emphasis on carcinoma. AB - Lectin binding analysis of Con A, SBA, PNA, WGA, HPA, RCA-I, DBA, and UEA-I was performed in two cases of normal human adrenal gland, four cases of adrenocortical hyperplasia, six cases of adrenocortical adenoma, and seven cases of adrenocortical carcinoma to examine the differences of lectin binding properties. No lectins were bound specifically to adrenocortical cells. Binding of RCA-I was observed in some carcinoma cells focally but not in benign counterparts. With WGA and Con A, the cytoplasmic binding became apparent in the cells manifesting hypercorticism. In adrenocortical carcinoma, various WGA and Con A binding patterns were intermingled, but no specific patterns were identified. The focal nature of RCA-I binding, and no specific WGA and Con A binding properties in carcinoma, suggest that diagnosis of malignant neoplasm must still largely rely on clinical, hormonal, and structural criteria in adrenocortical neoplasms. PMID- 2910231 TI - Medulloblastoma with cartilaginous differentiation. AB - We describe the histologic, immunocytochemical, and electron microscopic features of a medulloblastoma containing cartilage that occurred in the left cerebellar hemisphere of a 57-year-old man. By light microscopy, highly cellular areas of the tumor typical of medulloblastoma showed evidence of both glial and neuroblastic differentiation. The tumor also contained foci of mature and immature cartilage. Transitions were observed between the cartilaginous foci and the more densely cellular regions of the tumor. No frankly teratomatous features or mesenchymal components other than cartilage were present. We postulate that the production of cartilage within this neoplasm most likely resulted from the metaplastic transformation of preexisting mesenchymal elements within the tumor or from multipotential neural crest-derived ectomesenchymal cells. Alternatively, the cartilage could have been produced directly by the neuroectodermal cells themselves, possibly related to a capacity for the latter to produce a chondroid ground substance. PMID- 2910232 TI - Fatal iatrogenic salicylate intoxication in a long-term user of enteric-coated aspirin. AB - A 64-year-old woman, who was taking long-term enteric-coated aspirin therapy for rheumatoid arthritis, was prescribed approximately twice her normal dosage (7.1 g daily) during a ten-day convalescence following surgery. Although she presented with features mimicking sepsis, biochemical analysis, ie, a spuriously high carbon dioxide content, suggested salicylate intoxication (admission salicylate concentration, 5.13 mmol/L). She died on the third day after admission. Autopsy showed no major source of infection except for bronchopneumonia. Long-term users of a high-dose aspirin are at risk for potential salicylate intoxication. The metabolism of salicylate, particularly its excretion kinetics, can make small upward dosage adjustments hazardous. Salicylate has widespread metabolic effects that can mimic other medical conditions, leading to delayed diagnosis of salicylate intoxication. Increased mortality and morbidity may result. PMID- 2910233 TI - Gastrointestinal arterial fibromuscular dysplasia of childhood. PMID- 2910234 TI - Ganglioneuromatous proliferation associated with juvenile polyposis coli. AB - A case of nonfamilial juvenile polyposis coli was associated ganglioneuromatous proliferation in the polyps is described. The ganglioneuromatous proliferation was characterized by clusters of mature ganglion cells and nerve fiber bundles in the lamina propria and submucosa of the juvenile polyps. The patient had no history of von Recklinghausen's disease or multiple endocrine neoplasia syndrome, type 2b. The implications of this peculiar finding are discussed and the literature is reviewed. PMID- 2910235 TI - Role models in pathology. A new look at an old issue. AB - Recent trends indicate that pathology is becoming a less attractive specialty to US medical graduates. This article discusses role models as an important but underutilized tool in medical education, and pathology education, in particular. Historically, the term role model has been used to describe a hero or a good teacher. Social scientists who study specialty choices in medicine, however, consider role model to be a much more heterogeneous concept. The information gained from these studies, therefore, needs to be sorted out carefully if erroneous conclusions about role models are to be avoided. For example, personality traits and attitudinal assessment studies encourage, unfortunately, either a totally passive stance toward recruitment, or a selective approach to those students who fit the specialty profile. However, there is no available evidence to support such approaches in pathology. Indeed, faculty role models have consistently been found to be influential recruiters into specialties that are not well known to the students (eg, pathology). Many different types of role models are present in pathology. Two important types are clinical consultants and physician-researchers. Positive faculty role models are an effective way to remove false impressions and negative assumptions about the practice of pathology, and they should be used more explicitly in recruiting efforts. PMID- 2910236 TI - The flip side of tumor immunity. AB - A large amount of data suggest that tumors are, to some degree, dependent for their growth on a positive level of immune reaction, a level that is unique for each tumor. Each tumor gradually adjusts its immunogenicity to the level that will, in the immunologic context of its own particular host, maximize its growth. Thus, it follows that immunosuppression may be as likely as immunoaugmentation to have a therapeutic effect. PMID- 2910237 TI - Recombinant human tumor necrosis factor alone and with chemotherapeutic agents. Effect on nude mouse-supported human bladder cancer heterografts. AB - Although studies done in tissue culture (in vitro) have shown synergism between recombinant human tumor necrosis factor (rhTNF) and chemotherapeutic agents, whether such synergism exists in a complex in vivo environment with acceptable toxic side effects has not been determined, to our knowledge. The effect of rhTNF alone and in combination with cisplatin, etoposide, doxorubicin, or dactinomycin on the growth of heterotransplants of human bladder transitional cell carcinoma was studied using a modified subrenal capsule assay in athymic nude mice. Only etoposide potentiated rhTNF cytotoxicity; no increase in host toxicity was noted. Variably enhanced toxic side effects were seen with other combinations. It is concluded that rhTNF combined with etoposide may have potential clinically exploitable therapeutic "synergism" in the treatment of advanced bladder cancer. PMID- 2910238 TI - Squamous cell carcinoma arising in previously burned or irradiated skin. AB - Squamous cell carcinoma (SCC) arising in previously burned or irradiated skin was reviewed in 66 patients treated between 1944 and 1986. Healing of the initial injury was complicated in 70% of patients. Mean interval from initial injury to diagnosis of SCC was 37 years. The overwhelming majority of patients presented with a chronic intractable ulcer in previously injured skin. The regional relapse rate after surgical excision was very high, 58% of all patients. Predominant patterns of recurrence were in local skin and regional lymph nodes (93% of recurrences). Survival rates at 5, 10, and 20 years were 52%, 34%, and 23%, respectively. Five-year survival rates in previously burned and irradiated patients were not significantly different (53% and 50%, respectively). This review, one of the largest reported series, better defines SCC arising in previously burned or irradiated skin as a locally aggressive disease that is distinct from SCC arising in sunlight-damaged skin. An increased awareness of the significance of chronic ulceration in scar tissue may allow earlier diagnosis. Regional disease control and survival depend on surgical resection of all known disease and may require radical lymph node dissection or amputation. PMID- 2910239 TI - Is limb-sparing surgery applicable to neurogenic sarcomas of the extremities? AB - The presentation, treatment, and outcome of 12 patients with high-grade neurogenic sarcoma (NS) of the extremity were compared with those of 21 patients with high-grade extremity soft-tissue sarcoma of nonneural origin in a retrospective study from January 1976 to January 1988. Pain and neurologic deficit were more common in the NS group. Limb-sparing surgery was carried out with equal frequency in both groups. Local recurrence was six times more frequent in the NS group at three-year follow-up (59% vs 10%). Width of resection margin was the dominant prognostic variable bearing on local control after limb-sparing surgery. Anatomic and functional constraints tended to limit resection margin in patients with NS arising from mixed motor-sensory or predominantly motor nerves. PMID- 2910240 TI - Patterns of recurrence after resection of osteosarcoma of the extremity. Strategies for treatment of metastases. AB - We studied recurrence patterns in 255 patients with high-grade osteosarcoma of the extremity and the efficacy of the treatment of these recurrences. One hundred seven patients developed metastatic disease: 77 had isolated pulmonary metastases, 17 had simultaneous metastases to lung and elsewhere, and 13 had metastases to other sites. Of the 77 patients with metastases confined to the lung, 51 (66%) underwent thoracotomy for resection of the metastases, and 13 (17%) are long-term disease-free survivors. Patients with simultaneous metastases to lung and other sites, and patients with metastases to sites other than lung, have a poor prognosis with only one long-term disease-free survivor in these groups. Thoracotomy has a limited role in the treatment of metastatic disease. Improvements in aggressive, systemic chemotherapy are essential for improving the prognosis in these patients. PMID- 2910242 TI - Debridement of wounds with Dakin's solution. PMID- 2910241 TI - Clinical experience with regional pancreatectomy for adenocarcinoma of the pancreas. AB - Twenty patients with adenocarcinoma of the pancreas underwent a regional pancreatectomy, including resection of the pancreas, regional lymphadenectomy, duodenectomy, antrectomy, and sleeve resection of the portal vein. Three patients required mesenteric arterial reconstruction. Adjunctive radiotherapy was administered to 17 patients, with 11 patients receiving intraoperative radiation and six patients receiving postoperative external-beam-radiation. Complications developed in 11 patients (55%), including infectious and septic events (five patients), biliary or enteric fistulas (two patients), mesenteric vascular thrombosis (two patients), and other complications (two patients). Four patients (20%) suffered treatment-related deaths. The overall median survival was 12.0 months. Survival at one year was 50% and, at three years, 10%. Two patients died of causes unrelated to cancer at 18 and 39 months, and one patient remains alive and free of disease 50 months following therapy. Morbidity and survival did not differ among patients who received intraoperative, conventional postoperative, or no radiation therapy. Although occasional patients may benefit with survivals of longer than three years, regional pancreatectomy carries major morbidity and produces little survival benefit for most patients with pancreatic cancer. PMID- 2910243 TI - Cancer surveillance after augmentation mammoplasty. PMID- 2910244 TI - The prognostic significance of lymph node metastases after preoperative chemotherapy for locally advanced breast cancer. AB - We compared the prognostic value of surgical lymph node staging after preoperative chemotherapy relative to other patient and tumor variables in 136 patients with locally advanced breast cancer (T3-4 and/or N2-3) who received preoperative chemotherapy followed by mastectomy and axillary dissection as part of a prospective protocol. Univariate analysis revealed that the number of metastatic lymph nodes, clinical tumor stage at presentation, clinical and pathologic response, and menopause status were significant variables associated with survival and disease-free survival, but clinical node stage at presentation and estrogen receptor status were not. The number of metastatic lymph nodes had more prognostic value than the other factors, and when evaluated by multivariate regression, surgical node staging added significantly more information to the remaining variables. Surgical staging is an important component of treatment for patients with breast cancer undergoing preoperative chemotherapy because it can provide an accurate and quantitative method for subgrouping patients with different survival rates and it can be used to compare results between preoperative chemotherapy trials. PMID- 2910245 TI - A comparison of palpable and nonpalpable breast cancers. AB - Chi-square statistics were used to compare prognostic factors of 60 patients with nonpalpable breast cancer (NPBC) and 112 patients with palpable breast cancer. Noninvasive cancers were more frequent, tumor size was smaller, and nodal metastasis was significantly less frequent in the NPBC group. However, the frequency of nodal metastasis was similar when adjusted for size and grade. There was no significant difference in the incidence of age and menopausal status of the patients, histologic types, hormone receptor status, and histologic/nuclear grade between these two groups. The findings were consistent with the hypothesis that NPBCs are potentially lethal tumors and that mammograms detect them earlier, ie, these tumors are smaller, localized, and, therefore, more curable. PMID- 2910246 TI - Results of surgical excision of one to 13 hepatic metastases in 98 consecutive patients. AB - Metastatic carcinoma to the liver is generally considered to be associated with a poor prognosis, with five-year survival of only 20% to 30% after resection of solitary lesions. Ninety-eight consecutive patients underwent the surgical removal of one to 13 metastatic lesions from the liver. A rising carcinoembryonic antigen level was considered an indication for reexploration. All gross tumor was removed in every patient; 66 had more than one metastasis. Survival was unexpectedly high: 91 of 98 were alive at 12 months, 50 (70%) of 71 at 13 to 24 months, 23 (66%) of 36 at 25 to 36 months, 14 (74%) of 19 at 37 to 48 months, six (60%) of ten at 49 to 60 months, four (80%) of five at 61 to 72 months, and two (50%) of four 73 to 84 months after resection of multiple liver metastases. The procedure appears to be a safe and, in some patients, beneficial surgical technique for the removal of multiple hepatic metastases. PMID- 2910247 TI - Experimental liver metastasis. Implications of clonal proclivity and organ specificity. AB - "Spontaneous" lung metastases develop in over 50% of the animals bearing subcutaneous isografts of WB-2054, a rat colon carcinoma. A metastatic variant has been developed by "Fidler" type in vivo selection, yielding 100% lung metastasis. In a five-week assay to test the organ specificity of this lung metastatic variant, however, "experimental" liver and lung metastases could be induced in 100% and 60% of animals on portal venous and intravenous injections, respectively. The results demonstrate selection of a metastatic variant from heterogeneous primary tumor, and suggest at least two interacting mechanisms: (1) mechanical (the anatomy of the blood-borne metastatic pathways) and (2) biologic (factors intrinsic to primary tumor subpopulations that can be selected for metastatic proclivity). In addition, liver metastases were successfully established from colon tumors induced by cecal wall injection of tumor cells. Such a spontaneous liver metastasis model will be useful to study the specific mechanisms involved during metastasis of colon cancer to the liver. PMID- 2910248 TI - Intra-abdominal recurrence of colorectal cancer detected by radioimmunoguided surgery (RIGS system). AB - Since 1986, 32 patients with metastatic colorectal cancer have undergone second look radioimmunoguided surgery (RIGS system). The primary tumor was located in the right and transverse colon in 11 patients, left and sigmoid colon in 16, and rectum in five. The carcinoembryonic antigen level was elevated in 30 patients (94%); all patients underwent a computed tomographic scan of the abdomen and pelvis. The overall sensitivity of the computed tomographic scan was 41% (abdomen other than liver, 27%; liver, 58%; and pelvis, 22%). The RIGS system identified recurrent tumor in 81% of the patients. The most common site of metastasis was the liver (41%), independent of the primary location. Local/regional recurrences alone accounted for 40% of all recurrences. In six patients (18%), recurrent tumor was found only with the RIGS system. The RIGS system is more dependable in localizing clinically obscure metastases than other methods, and carcinoembryonic antigen testing remains the most accurate preoperative method to indicate suspected recurrences. PMID- 2910249 TI - Rationale for aggressive colonoscopy in patients with colorectal neoplasia. AB - The role of colonoscopy in patients with colorectal neoplasia is not well established. The results of colonoscopy, from 1982 through 1987, in 42 patients with cancers who underwent preoperative colonoscopy (group 1), 64 patients with benign polyps (group 2), and 51 patients who were examined only postoperatively (group 3) were reviewed. These results indicated that (1) approximately one third of all findings would have been missed if endoscopy had been performed to only 60 cm; (2) there was a high incidence of synchronous lesions (33.3%) in group 1 and 34.4% in group 2); (3) 57% of patients with synchronous cancer and 63.6% of patients with synchronous polyps developed metachronous lesions, compared with 10.7% and 11.9% of patients with a single lesion; (4) there was a higher incidence of metachronous lesions seen in group 3, compared with group 1; and (5) the median interval for noting metachronous lesions in patients who underwent colonoscopy preoperatively was approximately 18 months. These findings endorsed preoperative colonoscopy and aggressive follow-up in patients with colorectal tumors. PMID- 2910250 TI - Prospective phase I trial of conservative management of low rectal lesions. AB - The purpose of this study was to assess and function and to compare the morbidity of local excision and postoperative radiotherapy for rectal adenocarcinoma with the morbidity of abdominoperineal resection. A posterior parasacral approach was used for local excision. All patients had negative margins, and all but one were continent after completion of radiotherapy. Seven patients (29%) had either a wound infection or a fistula in the local excision group. No local failures occurred, although follow-up was only 13 months. Thirteen (50%) of the 26 patients who underwent an abdominoperineal resection developed at least one complication. Combined treatment that spares the rectal sphincters may be preferable in selected patients with low rectal cancer, if long-term disease-free survival is maintained. PMID- 2910251 TI - Staging renal carcinoma. What is sufficient? AB - We retrospectively reviewed the roentgenographic and pathologic staging of 64 patients with renal cell carcinoma to assess the role of the various staging modalities (ie, angiography, venacavography, bone scanning, ultrasound, computed tomography [CT], and magnetic resonance imaging). Specific attention was directed at detecting vena cava thrombus and metastatic bone disease, factors with a significant impact on the therapeutic approach. The findings support the role of CT as the principle tool for overall staging and the observation that venacavography is not indicated if CT has excluded caval thrombus. Similarly, routine bone scans are not warranted in the absence of an elevated alkaline phosphatase level or bone pain. The key to the more efficient utilization of imaging resources is understanding the capabilities of the technology available. PMID- 2910252 TI - Natural killer sensitivity of colorectal carcinoma targets. Correlation with degree of differentiation. AB - Lymphocytes with natural killer (NK) ability recognize a wide range of target cells; however, the mediators of specific target recognition are still largely unknown. Despite the diversity of the NK target repertoire, it is typified by cells of relatively immature phenotype. The purpose of this study was to determine if colorectal carcinoma (CRC) targets were sensitive to spontaneous lysis by fresh human NK effector cells and to observe the role of CRC differentiation in this process. Results demonstrated that poorly differentiated CRC targets were susceptible to NK-mediated lysis whereas CRC targets with more differentiated structure were NK resistant. In addition, chemical induction of a more mature CRC phenotype confers NK resistance on a previously NK-susceptible target. This maturation-related modulation of NK sensitivity can provide a model with which to further study interaction between NK cells and CRC targets. PMID- 2910254 TI - Agenesis of the corpus callosum and limbic malformation in Apert's syndrome. PMID- 2910253 TI - Cachectin activity in the serum of cachectic, tumor-bearing rats. AB - Cachectin/tumor necrosis factor has been postulated to be a possible mediator of cancer cachexia. Using a sensitive bioassay, we attempted to detect circulating cachectin activity in the serum of sarcoma-bearing rats and to correlate levels with measurements of cachexia and the extent of disease. In addition, we resected the tumor to determine the time course of reversal of cachexia and the disappearance of cachectin activity in the serum. Circulating cachectin activity was not detectable in the serum of non-tumor-bearing rats or in tumor-bearing rats until 28 days after implantation. With evidence of food intake and body weight decline, cachectin activity became detectable in the serum and levels increased as cachexia and tumor burden increased. Serum cachectin activity levels correlated directly with tumor burden and inversely with food intake and body weight change. After resection of the tumor, food intake and body weight increased and serum cachectin activity became undetectable. Serum triglyceride levels were higher in cachectic tumor-bearing rats than in pair-fed non-tumor bearing controls, and levels decreased after tumor resection as cachectin activity decreased. The results suggest that cachectin is a humoral mediator of cachexia in this rat-tumor model. PMID- 2910255 TI - Angiography in pure motor hemiparesis due to meningovascular syphilis. PMID- 2910256 TI - Plasma physostigmine concentrations after controlled-release oral administration. PMID- 2910257 TI - Magnetic resonance imaging in moyamoya disease. PMID- 2910258 TI - Talking to comatose patients. PMID- 2910259 TI - A community-based study of parental age at the birth of patients with dementia of the Alzheimer type. AB - The association of dementia of the Alzheimer type (DAT) with parental age at the birth of patients who develop DAT was investigated in a community-based study in Japan. Both maternal and paternal ages of patients who have developed DAT are significantly higher than those in controls and multi-infarct dementia. This study suggests that advanced age may become a cause of chromosome abnormality, and advanced parental age at subjects' birth may be a possible risk factor in DAT. PMID- 2910260 TI - Neuropsychological test findings in subjects with leukoaraiosis. AB - Focal periventricular white-matter changes (leukoaraiosis) have been identified incidentally on brain imaging in normal healthy individuals and more commonly in the elderly and in hypertensive individuals. It has been suggested that leukoaraiosis represents the early stages of Binswanger's leukoencephalopathy, a dementing process thought to be related to hypertensive cerebrovascular disease. To test this hypothesis, extensive neuropsychological tests were administered to 50 consecutive normotensive, middle-aged, healthy volunteers. Ten subjects (20%) had white-matter changes on magnetic resonance scans; 40 subjects (80%) had normal scans. The differences observed on neuropsychological testing between subjects with and without leukoaraiosis were not significant. While this study argues against a link between leukoaraiosis and dementia, prospective longitudinal studies are needed to determine the value of leukoaraiosis in predicting future cognitive decline. PMID- 2910261 TI - Altered norepinephrine metabolism in Shapiro's syndrome. AB - We studied a 66-year-old woman with spontaneous periodic hypothermia (Shapiro's syndrome) to determine the mechanisms that result in increased plasma norepinephrine (NE) levels. In comparison with age-matched control subjects, compartmental analysis of NE kinetics revealed an increased NE release rate into the extravascular compartment and decreases in NE clearance and volume of distribution of NE in the intravascular compartment. Clonidine therapy was associated with an initial dramatic decrease in the frequency of diaphoretic episodes as well as with a fall in NE release rate and increases in NE clearance and volume of distribution. We conclude that increased NE release and decreased plasma NE clearance result in elevated plasma NE levels in Shapiro's syndrome. Clonidine, which was associated with changes in NE kinetics, may provide effective treatment for this disorder. PMID- 2910262 TI - The spinal accessory nerve in childhood hemiplegia. AB - Fifteen of 17 children with hemiplegia were found to have weakness of the trapezius muscle but a normally functioning sternocleidomastoid muscle. Very few other cranial nerve-mediated deficits were found. The difference between the two muscles, both supplied by the spinal accessory nerve, may depend on a phylogenetic basis, with the former behaving like an appendicular muscle and the latter like an axial muscle. PMID- 2910263 TI - Lexical agraphia in Alzheimer's disease. AB - We studied spelling in 11 patients with senile dementia of the Alzheimer type (SDAT), and their performance was contrasted with that of normal controls. A consistent and specific pattern of linguistic agraphia was identified in the group with SDAT. Although patients with SDAT spelled regular words and nonwords as well as controls, they performed significantly worse when they spelled irregular words. These findings indicated an impairment of the lexical spelling system, consistent with the diagnosis of lexical agraphia. Our observations suggested a loss of word representations from the orthographic lexicon in SDAT and/or an inability to access these representations. However, phonological spelling (phoneme-grapheme conversion) was largely spared. PMID- 2910264 TI - Tendon reflex asymmetry by voluntary mental effort in healthy subjects. AB - The effect of voluntary mental influences on the tendon reflexes was examined in healthy subjects. The patellar reflexes were evoked by a method comparable with the clinical examination, and the reflexes were recorded by surface electrodes. Eighteen subjects were instructed to increase and then decrease the right patellar reflex by mental effort, without contracting any muscles. Most subjects increased the reflex in both conditions. Subsequently, ten subjects were instructed to increase the right patellar reflex and decrease the left by mental effort. Measurement showed reflex asymmetry in seven subjects consistent with the instruction. The experiment was repeated in another 20 subjects with symmetric reflexes at rest. Ten of these subjects were, after random assignment, instructed to increase either the right or the left knee jerk. All subjects (and an additional 15 asymmetric control subjects) were examined by a neurologist without knowledge of the instruction. Three of the ten instructed subjects were correctly judged to be asymmetric, but the agreement between instruction and neurologic judgment was not statistically significant. Mentally induced reflex asymmetry is possible, and may be clinically relevant in some cases. PMID- 2910265 TI - Etiology and mortality of status epilepticus in children. A recent update. AB - We reviewed the medical records of 218 episodes of status epilepticus in 193 children who were admitted to the hospital between 1983 and 1987. Of the episodes, 61% were in boys and 39% in girls, with an age range of 1 month to 14 years (average, 3.2 years). The majority of episodes (73%) occurred in patients who were less than 5 years old, with 61% less than 3 years old and 28% less than 1 year old. Status epilepticus as the initial seizure occurred in 71% of episodes. In patients under 1 year of age, 75% of episodes were associated with acute causes (bacterial meningitis in 28% and electrolyte disorders in 30%), and 23% were idiopathic (19% associated with fever). In children less than 3 years old, 47% of episodes had an acute cause, 9% had a previously known seizure disorder, and 32% were idiopathic (30% associated with fever). In patients older than 3 years, 28% of episodes were associated with acute causes, 38% were known epileptics, and 13% were idiopathic (11% had fever). Overall mortality was 6%, with 1% of all episodes ending in death during the presenting seizure. We conclude that the etiology of status epilepticus is age related, with acute causes being more common in patients with a younger age at presentation. When our data are compared with other large studies in children, it appears that mortality associated with status epilepticus has decreased. PMID- 2910266 TI - Chronic isolated sixth nerve palsies. AB - Twenty-seven cases of chronic isolated abduction deficit, seen in 25 years of neuro-ophthalmology consultation, were reviewed. "Isolated" was defined as the lack of any other neurologic or ophthalmologic findings for at least six months. Cases were further subdivided into the categories of true and pseudo-abducens paresis. The origin, diagnosis, and management of long-standing abducens palsies were determined. Cases of pontine glioma, chordoma, chondrosarcoma, and meningioma that presented as an isolated abducens palsy and remained undiagnosed for at least six months were reviewed. PMID- 2910267 TI - Acute failure of forebrain with sparing of brain-stem function. Electroencephalographic, multimodality evoked potential, and pathologic findings. AB - We describe a case of acute failure of forebrain with preservation of brain-stem function following cardiopulmonary arrest. This condition is distinguished from persistent vegetative or noncognitive states. Multimodality evoked potentials showed electroretinograms but no cerebral potentials to flash stimulation of both eyes; normal electrocochleograms and brain-stem auditory-evoked potentials to click stimulation of both ears; and Erb's point, N13, and P14 but no cortical responses to electrical excitation of both median nerves. Pathologic alterations consisted of pseudolaminar necrosis involving the whole cerebral cortex and other forebrain regions, with relative preservation of brain stem and spinal cord. Close correspondence existed between electrophysiologic, clinical, and major neuropathologic alterations. PMID- 2910268 TI - Gentamicin toxicity in the primate retina. AB - To study the toxic effect of aminoglycoside antibiotics in the primate retina, gentamicin sulfate was injected into the center of the vitreous cavity of Cebus navrigatus monkeys. At a dose of 1000 to 3000 microgram, a picture consistent with apparent macular infarction appeared on fundus examination and fluorescein angiography by three days and gradually faded by 21 days. While light and electron microscopic examination of the retina showed no primary vascular lesions, striking damage to the inner retinal layers, mainly the nerve fiber layer, ganglion cell layer, and the inner plexiform and nuclear layer, was seen. Less severe effects in the outer retinal layers and the retinal pigment epithelium occurred. These observations suggest that the neurotoxic effect of intravitreal gentamicin was sufficient to cause a complete shutdown of the regional blood flow, perhaps by the mechanism of granulocytic plugging of the capillary bed. Although this toxic effect occurred at doses considerably in excess of what has been recommended for clinical use in humans, the "safe" dose of intravitreal gentamicin, nevertheless, remains to be established unequivocally. PMID- 2910269 TI - Photoablation of ocular melanoma with a high-powered argon endolaser. AB - We studied the use of a 15-W argon blue-green laser in the treatment of choroidal melanoma in a rabbit model. Greene melanoma cells were used to produce 2- to 4-mm thick tumors posteriorly in the suprachoroidal space in pigmented rabbits. Endophotocoagulation delivered through a 600-micron fiberoptic probe was performed to ablate the tumor tissue and a surrounding margin of normal tissue. A vitreous cutter was used simultaneously to remove liberated necrotic debris. The effect of the laser on tumor and normal ocular tissue was evaluated by light microscopy and the extent of the proliferative response by tritiated thymidine radioautography. Application of 100 to 400 pulses of laser energy using treatment parameters of 12 to 14 W of power and 0.1-s pulses resulted in complete ablation of melanoma tissue, overlying retina, and choroid. There was no substantial intraoperative or postoperative hemorrhage. Material liberated during the laser treatment was found to be nonviable. The effect of the laser on tissue appeared localized to within approximately 1.25 mm of the margin of the central lesion. The high-energy argon laser seems to offer a means of effectively ablating melanoma tissue via an internal resection approach. PMID- 2910270 TI - Response of pig retinal pigment epithelium to laser photocoagulation in organ culture. AB - Laser photocoagulation was applied in vitro to organ culture exoplants of porcine retinal pigment epithelium (RPE) attached to Bruch's membrane. Four-millimeter round buttons of eye wall containing RPE, choroid, and sclera were treated with 25 spots from the argon blue-green laser using 300 mW of power, a 500-micron spot size, and 0.1-s duration. Laser photocoagulation disrupts individual RPE cells acutely and lifts damaged RPE cells from Bruch's membrane. Treated areas become covered with irregular mounds of RPE cells within seven days. The acute damage and subsequent repair of the RPE in organ culture mimic the response of the RPE following laser photocoagulation in vivo. Thus, the morphologic response of the RPE to laser photocoagulation is an intrinsic property of this tissue that does not depend on the presence of the overlying retina. PMID- 2910271 TI - Ultrastructural location of extracellular matrix components in the optic nerve head. AB - The distributions of laminin and collagen types I through V were determined in optic nerve heads of cynomolgus monkeys using colloidal gold immunoelectron microscopy. Collagen types I and III localized to striated collagen fibrils in arterial walls throughout the optic nerve head and to fibrils comprising the core of the lamina cribrosa beams and optic nerve septa. Collagen type IV and laminin localized to basement membranes of all blood vessels and to basement membranes of astrocytes that lie between the laminar beams and line the optic nerve septa and pia mater. Collagen type V was detected both in striated collagen fibrils and in vascular and astrocyte basement membranes. These results provide a detailed understanding of the optic nerve head extracellular matrix distribution and illustrate a sensitive method for future study of its role in glaucomatous optic nerve damage. PMID- 2910272 TI - Malignant melanoma of the choroid with vitreal seeding. PMID- 2910273 TI - Excimer laser instrumentation and technique for human corneal surgery. AB - The design and development of the instrumentation utilized during the clinical and histopathologic evaluations of the first human eyes treated by argon fluoride excimer laser radiation are described. The laser, optical, alignment, measurement, and control subsystems required for this research were constructed to create a laser beam that has an axially symmetric energy distribution, can be calibrated and measured, can be aligned with the target tissue, and can be manipulated to excise surface tissue. The use of this excimer laser system has demonstrated that a nonuniform superficial lamellar keratectomy can be produced to excise areas of opacified, scarred, or abnormal cornea or to create a new anterior corneal curvature in attempts to correct refractive errors. PMID- 2910275 TI - Use of ophthalmic ointment to separate adhesive. PMID- 2910274 TI - Application of minute amounts of glue to the cornea. PMID- 2910276 TI - Genetic subtypes in retinitis pigmentosa. PMID- 2910277 TI - Increase in short-term fluctuation may be a clue for differentiating dystrophic from acquired defects in anterior visual pathways. PMID- 2910278 TI - Interest in the report of a new treatment. PMID- 2910279 TI - Optic disc rim area, pallor, and nerve fiber course. PMID- 2910280 TI - Rhodococcus equi endophthalmitis. Case report. PMID- 2910281 TI - Visual disturbance resulting from intranasal steroid injection. Case report. PMID- 2910282 TI - The Ethics Committee of the American Academy of Ophthalmology. PMID- 2910283 TI - Trends of the ophthalmic literature from 1955 to 1985. PMID- 2910284 TI - Bilateral anterior transposition of the inferior obliques. AB - Sixty-one children with bilateral overaction of the inferior oblique muscle with concurrent or previous infantile esotropia received bilateral inferior oblique recessions with anteriorization to a point 2 to 4 mm anterior to the lateral end of the inferior rectus insertion. Subsequent reoperation for recurrent overaction of the inferior obliques was needed in only one case. Also, substantial reduction in dissociated vertical deviation (DVD), when present, and almost complete absence of subsequent need for surgery for DVD among the 61 children of this series were new findings. Only one of the 61 required subsequent surgery for manifest DVD. In another series of 60 infantile esotropes of similar ages drawn from the same practice who had previously had no inferior oblique surgery, nine needed surgery for DVD. This difference (one of 61 vs nine of 60) was significant. PMID- 2910285 TI - Management of monocular congenital cataracts. AB - From 1971 through 1985, a diagnosis of monocular congenital cataract was made in 14 consecutive patients. All patients had a visually significant cataract that was documented at birth or within 2 months of age. All patients were followed up long enough to report distance linear recognition acuity. Excellent visual acuity (V/A) correlated with earlier surgery, earlier contact lens fit, and excellent amblyopia therapy compliance. The oldest age for attainment of excellent or good V/A was 17 weeks. Patching therapy was based on the binocular fixation pattern. The patching program consisted of 50% occlusion until the age of 2 months and gradually increased to 100% occlusion after the age of 7 months. Six patients (43%) attained excellent V/A (greater than 20/50), with three patients (21%) attaining good V/A (20/60 to 20/100) and five patients attaining poor V/A (less than 20/100). PMID- 2910286 TI - Ocular manifestations of the congenital varicella syndrome. AB - Three children developed the congenital varicella syndrome following a maternal varicella infection during the second trimester of pregnancy. Systemic findings included a bulbar palsy, mild hemiparesis, cicatricial skin lesions, developmental delay, and learning difficulties. Ocular findings included chorioretinitis, atrophy and hypoplasia of the optic discs, a congenital cataract, and Horner's syndrome. Electroretinograms and pattern-reversal visual evoked potentials recorded from the four eyes with chorioretinitis were attenuated and degraded. Two of the children had been misdiagnosed as having congenital toxoplasmosis. Chorioretinal scars probably occur more frequently with the congenital varicella syndrome than has been previously recognized and should be included in the differential diagnosis of congenital chorioretinal scars. Hypoplasia of the optic disc may develop after an intrauterine varicella infection during the 16th week of gestation. Children with the congenital varicella syndrome should be examined by an ophthalmologist to exclude ocular abnormalities. These abnormalities are often subtle and difficult to diagnose correctly. PMID- 2910287 TI - Tonic upgaze in infancy. A report of three cases. AB - Episodic conjugate tonic upgaze unassociated with seizures or downgaze palsy was noted in three infants during the first months of life. With age, the episodes became shorter and less frequent and were most notable during periods of fatigue or illness. This phenomenon may be analogous to transient tonic downward deviation of the eyes in healthy infants. PMID- 2910288 TI - Lens fluorescence in relation to metabolic control of insulin-dependent diabetes mellitus. AB - The correlation of blue-green lens fluorescence to the metabolic control of insulin-dependent diabetes mellitus was studied in 36 patients in whom the level of glycosylated hemoglobin A1c (HbA1c) had been followed from the onset of diabetes. Good metabolic control (22 patients, all with mean HbA1c levels, less than 7.0% and, thus, low blood glucose concentrations) was associated with less lens fluorescence and a higher lens transmittance than poor metabolic control (14 patients, all with mean HbA1c levels, greater than 9.7%). It appears that in diabetes, an increase in lens fluorescence and a decrease in lens transmittance are delayed by good metabolic control, and that the determination of lens fluorescence provides information about the long-term control of diabetes. PMID- 2910289 TI - Various stages of optic neuritis assessed by subjective brightness of flicker. AB - In the Aulhorn flicker test, the subjective brightness of a steady field is matched to that of a flickering field at 50 to 0 Hz. The test gives pathologic values only for active optic neuritis (ON) and gives normal results for normal eyes and eyes with subsided ON and other diagnoses, with a specificity of 98% and a sensitivity of 85.5%. Characteristic variations of the curves of subjective brightness during the course of ON allow a subtle assessment of five different disease stages, and there is a clear distinction between various disease patterns, ie, acute, chronic, recurrent, diminishing, and subsided ON. This distinction is impossible on the basis of visual evoked potentials. The test can be done easily and quickly without major technical equipment, even in an ophthalmologist's office. PMID- 2910290 TI - Chemotactic activity of aqueous humor. A cause of failure of trabeculectomies? AB - The chemoattractant activity for ocular fibroblasts of the aqueous humor of patients undergoing glaucoma surgery was evaluated in 48-well microchemotaxis chambers and compared with control specimens from patients undergoing cataract extractions. All specimens were chemoattractant, but those from patients who had previously undergone glaucoma surgery that had failed were of significantly greater activity than the controls'. This chemoattractant activity is primarily chemotactic. It consists of heat-stable and heat-labile components. The predisposition of a patient to sustain failed glaucoma drainage surgery may be related to the chemoattractant activity of his aqueous humor, since strongly chemoattractant aqueous humor may encourage fibrosis at the operation site. PMID- 2910291 TI - Treatment of carotid-cavernous sinus fistulas using a detachable balloon catheter through the superior ophthalmic vein. AB - Four consecutive patients with carotid-cavernous sinus fistulas that could not be treated by the standard techniques of endoarterial balloon occlusion or embolization were successfully treated by advancement of a detachable balloon catheter through the ipsilateral superior ophthalmic vein. Under angiographic monitoring, the balloon was passed into the cavernous sinus, inflated to close the fistula, and detached. Three of the patients had a spontaneous fistula, and one had a traumatic fistula that had previously been trapped unsuccessfully. All patients had complete resolution of symptoms and signs after occlusion of the fistula. There were no intraoperative or postoperative complications. The transvenous approach to the cavernous sinus through the superior ophthalmic vein is a safe, effective treatment of carotid-cavernous sinus fistulas, whether they are direct or dural in nature. PMID- 2910292 TI - Minocycline levels in tears of patients with active trachoma. AB - We determined minocycline levels in human tears and plasma samples using high performance liquid chromatography. In the first study, we determined the trough tear and plasma levels of minocycline in patients with active trachoma 24 hours after an oral dose. After a single dose of minocycline, the mean concentration of the drug in tear samples was 189 +/- 58 ng/mL and corresponding plasma levels were 578 +/- 290 ng/mL. In a second study, we monitored the pharmacokinetics of the drug in tear and plasma samples of healthy nonfasting adults. Tear and plasma samples were collected at 1 through 6, 12, 24, 48, 72, and 96 hours. The pharmacokinetics study revealed that 48 hours following a single 200-mg dose of minocycline, the mean tear level of minocycline was 68 ng/mL, which is above the in vitro minimal inhibitory concentration required for Chlamydia trachomatis and other susceptible organisms. PMID- 2910293 TI - A comparison of retrobulbar and periocular anesthesia for cataract surgery. AB - Complications of retrobulbar anesthesia are rare but significant. Periocular anesthesia has been advocated as an alternative to retrobulbar injections. In a prospective, randomized, masked study of 79 consecutive cataract extractions with intraocular lens implantations, 40 patients received retrobulbar injections and 39 patients received periocular injections. In every instance, the volume of the injection was 5 mL. No significant difference in surgeon's assessment of akinesia and anesthesia was found. Supplemental anesthesia was required in eight (21%) of the patients who received retrobulbar injections and in 11 (28%) of the patients who received periocular injections. A significant increase in chemosis was found with periocular injections. There was one complication with retrobulbar anesthesia and none with periocular anesthesia. No significant difference in patient assessment of comfort was found. The efficacy of periocular anesthesia appears to be comparable to that of retrobulbar anesthesia. PMID- 2910294 TI - The ultrastructural pathological features of congenital microcoria. A case report. AB - We describe the light microscopic, immunohistochemical, and electron microscopic findings in a sporadic case of congenital microcoria in a 72-year-old man with senile cataract. We demonstrated a lack of myofilaments and desmin in the stromal cytoplasmic processes of the anterior pigmented cells of the iris, although other features of muscle differentiation were present in these few surviving cell processes that normally form the pupil dilator muscle. Degenerative changes in anterior pigment cells and iris stromal atrophy were thought to be late secondary features of microcoria. The findings suggest that congenital microcoria results from a defect of intermediate filaments in the terminal fetal stages of differentiation of the anterior pigmented epithelial cell of the iris, with absence of myofilaments and consequent failure of development of a functional dilator pupil muscle. PMID- 2910295 TI - Binding of pirprofen to human serum albumin studied by dialysis and spectroscopy techniques. AB - The interaction of pirprofen with human serum albumin (HSA) was investigated by equilibrium dialysis and spectroscopic (UV absorption, fluorescence, CD, NMR) techniques. It was found that HSA binds pirprofen nonstereospecifically. The binding of pirprofen depends upon the N-B conformational change of albumin. Chloride ions appear to displace the drug from its binding site. The thermodynamic parameters suggest that the interaction may be explained by electrostatic as well as hydrophobic forces. The absorption spectral changes which accompanied the binding of pirprofen to HSA implied that the aromatic portion of drugs was inserted into the hydrophobic crevice in the protein, while the carboxyl group of the drug interacted with a cationic site on the albumin surface. The NMR data indicated that the pyrroline ring and propionic acid parts may be the major binding site for HSA. A specific binding site for pirprofen on the HSA was found to be site II, benzodiazepine site, using fluorescence probes and drug markers. In addition, from the binding data with modified HSA, it seems that Tyr-411 is specifically involved in pirprofen binding. PMID- 2910296 TI - Effect of 4-methylpyrazole on ethanol-induced decrease in rat plasma amino acids. AB - It has been shown earlier that an acute dose of ethanol causes an immediate decrease in the concentration of most plasma amino acids, and that this decrease involves both beta-adrenergic and adrenocortical mechanisms. In this work is shown that the oxidation of ethanol also plays an important role in the amino acid decreasing effect. Male rats were pretreated with 4-methylpyrazole, an inhibitor of liver alcohol dehydrogenase, in doses causing an 85% inhibition of the ethanol elimination. In this group the ethanol-induced decrease in amino acids was much less pronounced than in a control group pretreated with saline. PMID- 2910297 TI - Comparative cytotoxicity, DNA synthesis inhibition and drug incorporation of eight anthracyclines in a model of doxorubicin-sensitive and -resistant rat glioblastoma cells. AB - We have compared the growth inhibition, DNA synthesis inhibition and cell incorporation of eight anthracyclines in a model of doxorubicin-sensitive and resistant rat C6 glioblastoma cells. The anthracyclines studied were both the reference molecules (daunorubicin, doxorubicin) and the new drugs recently introduced in clinical use or in trials (epirubicin, idarubicin, pirarubicin, esorubicin, rubidazone, 4'-deoxy-4'-iododoxorubicin). We have shown that the in vitro growth inhibition was correlated with the LD50. The new anthracyclines were more potent than the reference drugs in the sensitive cells and the resistance patterns revealed a reduced cross resistance of idarubicin, pirarubicin and 4' deoxy-4'-iododoxorubicin towards the doxorubicin-resistant line. DNA synthesis inhibition occurred for much higher doses than growth inhibition in sensitive cells, but for similar doses in resistant cells. This suggests that different mechanisms could be involved in the mechanism of growth inhibition in sensitive and resistant cells. For similar exposures, reduction of drug incorporation was a general feature in the resistant line when compared to the sensitive one. However, no correlation was shown, for the various drugs, between the reduction of incorporation and the resistance factor. Moreover, the intracellular concentration required for growth inhibition is much higher in resistant cells than in sensitive cells, suggesting that increased drug efflux might not be the only mechanism to explain drug resistance. PMID- 2910298 TI - Pulmonary disposition of the potent glucocorticoid budesonide, evaluated in an isolated perfused rat lung model. AB - Budesonide is a potent glucocorticoid developed for the local treatment of respiratory disorders such as bronchial asthma and allergic rhinitis. We now report the lung disposition of 3H-budesonide administered either via the air passages or via the pulmonary circulation using isolated perfused and ventilated rat lungs. A rapid initial absorption was found after intratracheal administration of a clinically relevant dose of the drug. However, about half of the given dose was slowly released into the lung perfusate. The lung uptake of budesonide from the pulmonary circulation was relatively high (lung extraction ratio about 0.12). These data points to a high lung affinity for budesonide. The drug was not biotransformed in the lung. The high lung affinity and absence of lung metabolism can be important factors to explain the good therapeutic effects seen with budesonide in the clinic. PMID- 2910299 TI - Chromatographic characterization of neurotoxic esterase. AB - Neurotoxic esterase (neuropathy target enzyme, NTE) is an enzyme whose irreversible inhibition is the apparent first step in the induction of organophosphorus-induced delayed neuropathy. NTE is an integral membrane protein and thus must be solubilized before isolation can be attempted. This study describes solubilization of active chicken brain NTE with the nondenaturing detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) and characterization of the detergent-solubilized enzyme by gel exclusion chromatography. When detergent-solubilized membranes were chromatographed on Sepharose gel exclusion media, NTE activity eluted with an apparent molecular weight of 880-970 kD. When [3H]diisopropylphosphorofluoridate-radiolabeled membranes and unlabeled microsomal membranes were CHAPS-solubilized, combined and chromatographed on Sepharose 4B, NTE activity coeluted with two radiolabeled proteins (Mr = 148 kD and Mr = 112 kD using sodium dodecyl sulfate-polyacrylamide gel electrophoresis with reducing conditions). Another radiolabeled protein (Mr = 92 kD) coeluted exclusively with inhibitor-resistant esterase activity. This study provides strong evidence that the 148 and 112 kD proteins are subunits of a multicomponent NTE complex. PMID- 2910301 TI - Hemoglobin catalysis of a monooxygenase-like aliphatic hydroxylation reaction. PMID- 2910300 TI - In vitro inhibition of hepatic steroid hydroxylation by tamoxifen, a series of tamoxifen analogues and related compounds. AB - The in vitro inhibition of the cytochrome P-450 (P-450) isozyme specific positional hydroxylation of androst-4-ene-3,17-dione (androstenedione) by the alkylamino containing compounds trans- and cis-tamoxifen, 4-hydroxytamoxifen, N desmethyltamoxifen, SKF 525-A and the non-alkylamino containing compounds tamoxifen metabolite E, and tamoxifen analogue U-23469 was assessed in pooled hepatic microsomes isolated from untreated male rats. P-450 IIA 1-mediated androstenedione 7 alpha-hydroxylation appeared refractory to inhibition, with the lowest I50s being approximately 200 microM (cis- and and trans-tamoxifen, 4 hydroxytamoxifen). (According to the recently recommended nomenclature for cytochromes P-450 (Nebert DW and Gonzalez FJ, Ann Rev Biochem 56: 945-993, 1987), rat hepatic cytochromes P-450 UT-A, PB-B, PCN-E and UT-F are encoded by genes IIC 11, IIB 1, IIIA 1/2 and IIA 1, respectively. I50s toward the P-450 IIC 11-, IIB 1 , and IIIA 1/2-catalysed reactions, androstenedione 16 alpha-, 16 beta- and 6 beta-hydroxylations, respectively, were generally in the range 70-190 microM. However, metabolite E exhibited a rather specific and potent capacity to inhibit androstenedione 16 alpha-hydroxylase activity (I50 = 18 microM). Since a number of alkylamine compounds have been shown to sequester microsomal P-450 as an inactive metabolite intermediate (MI), the tamoxifen analogues were investigated for their in vitro MI complexation capacity. However, spectral binding studies revealed that the incubation of these compounds with NADPH-fortified microsomal fractions did not result in MI complex formation. In binding experiments conducted with oxidised microsomal fractions it was apparent that most of the tamoxifen analogues are type I ligands of quite high affinity for ferric P-450 (Ks range 10-60 microM). It seems unlikely that MI formation is involved in the observed inhibition of androstenedione hydroxylation by tamoxifen and congeners. Instead, and in contrast to the situation observed with SKF 525-A, it would appear that the inhibitory capacity of the tamoxifen analogues is more closely related to type I binding capacity with ferric P-450. A finding of particular interest is that metabolite E, in which the alkylamino side-chain is absent, elicited a type I interaction of high capacity. The maximal absorbance change of the type I interaction of this compound with microsomal P-450 was about three fold greater than the other compounds.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2910302 TI - Effects of maternally administered cimetidine during lactation on the development of drug metabolizing enzymes in mouse pups. PMID- 2910303 TI - Effect of glutathione depletion on morphine toxicity in mice. PMID- 2910304 TI - Prevention by antioxidants of oxidative damage to rabbit kidneys subjected to cold ischaemia. PMID- 2910305 TI - Thermodynamic studies on the interactions of di-substituted anthraquinones with DNA. PMID- 2910306 TI - Partial characterization of an enzyme that hydrolyzes sarin, soman, tabun, and diisopropyl phosphorofluoridate (DFP). AB - The properties of a rat liver enzyme that hydrolyzes organophosphorus (OP) inhibitors of cholinesterases were studied. The rates of hydrolysis of OP inhibitors were determined by continuous titration of released hydrogen ions, using a pH stat method. Centrifugation of homogenates at 205,000 g for 30 min demonstrated that the activity was in the soluble fraction. Hydrolysis of sarin, soman, and diisopropyl phosphorofluoridate (DFP), but not of tabun, was stimulated by the addition of Mn2+ and Mg2+. Hydrolysis of sarin greater than soman greater than tabun greater than DFP. Unlike other OP hydrolases that preferentially hydrolyze the non-toxic isomers of soman, this enzyme hydrolyzed all four soman isomers at approximately the same rate. This result was obtained in vitro by gas chromatographic analysis of enzyme-catalyzed soman hydrolysis and confirmed in vivo by demonstrating reduced toxicity in mice of soman partially hydrolyzed by this enzyme. Km and Vmax were determined by fitting V vs [S] to a hyperbolic function using regression analysis. Km values ranged from 1.1 mM for soman to 8.9 mM for tabun. Vmax values ranged from 54 nmol/min/mg protein for DFP to 2694 for sarin. The enzyme was stable for at least 2 months at -90 degrees but was inactivated by heating at 100 degrees for 5 min. Elution profiles from gel filtration by high pressure liquid chromatography showed that the hydrolytic activity for the OP inhibitors eluted in a single peak, suggesting that a single enzyme was responsible for the observed hydrolysis. Further purification and characterization of this enzyme should prove useful for the development of methods for detection, detoxification, and decontamination of these cholinesterase inhibitors. PMID- 2910307 TI - Effects of adriamycin and etoposide on the replication of adenovirus 5 in sensitive and resistant human tumour cells. AB - Adenovirus is a potential probe for identifying and understanding drug sensitivity in primary, nonproliferating cultures of human normal and tumour cells but the scope and limitations of such an approach first need to be evaluated in established cell lines. For this purpose we have identified an ovarian tumour cell line (CI-80-13S) with natural resistance to adriamycin, etoposide and crosslinking agents compared with other human tumour lines. Resistance to adriamycin correlated poorly with resistance to etoposide in these cell lines (r = 0.05). Adenovirus replication in drug-treated cells (viral capacity) was found to be differentially inhibited in sensitive cells when the drug was administered to cells simultaneously with infection (adriamycin) or 20 hr after infection (etoposide). Viral capacity could not be inhibited by more than 90% in sensitive cells. In contrast, no such plateau was exhibited in the dose-responses of cell survival or inhibition of cellular DNA synthesis, both of which distinguished sensitive from resistant cells. Adenovirus was not inactivated by preincubation with high doses of adriamycin or etoposide, thus confirming that no functionally-relevant damage is directly induced by these agents in DNA. Uptake of adriamycin and etoposide was similar in sensitive and resistant cells and both agents blocked cells in the G2 phase of the cell cycle. Protein-linked DNA was induced in sensitive cells. The results indicate that (a) these drugs have two dose-dependent effects in cells, one of which does not inhibit replication of adenovirus; and (b) inhibition of adenovirus replication could in principle be used to predict sensitivity to adriamycin and etoposide. PMID- 2910308 TI - Perturbation of liver microsomal calcium homeostasis by ochratoxin A. AB - The effect of ochratoxin A on hepatic microsomal calcium sequestration was studied both in vivo and in vitro. The rate of ATP-dependent calcium uptake was inhibited by 42-45% in ochratoxin A intoxicated rats as compared to controls. In the presence of NADPH, addition of ochratoxin A (2.5 to 100 microM) caused a concentration-dependent inhibition of calcium uptake (28-94%) by untreated rat liver microsomes. The rate of NADPH-dependent lipid peroxidation, measured as malondialdehyde formed, was also greatly enhanced by ochratoxin A. Various agents that inhibited ochratoxin A enhanced lipid peroxidation were also able to block the destruction of calcium uptake activity. Lipid peroxidation enhanced by ochratoxin A was also accompanied by leakage of calcium from calcium-loaded microsomes. These results suggest that ochratoxin A disrupts microsomal calcium homeostasis by an impairment of the endoplasmic reticulum membrane probably via enhanced lipid peroxidation. PMID- 2910309 TI - Presence of cytosolic aldehyde dehydrogenase isozymes in adult and fetal rat liver. AB - A colony of Wistar-strain rats bred at Purdue University was composed of animals with two different isozyme patterns of liver cytosolic aldehyde dehydrogenase (EC 1.2.1.3, ALDH) as determined by isoelectric focusing. One cytosolic isozyme pattern had a major activity band with a pI = 5.8 and a minor activity band at pI = 6.2. The other pattern contained three major isozymes with pI values of 5.3, 5.4 and 5.6 along with the pI 6.2 isozyme and a trace of the 5.8 one. The 5.8 and 6.2 isozymes were recognized by antibodies produced against horse and beef liver cytosolic ALDH, whereas the set of three (5.3-5.6) were not. The cytosolic isozymes were inhibited by low levels of disulfiram and had Km values for acetaldehyde in the 100 microM range, properties typical for cytosolic ALDHs. All animals contained the same isozymes of liver mitochondrial ALDH. These were a major activity with a pI = 5.2 and minor activities associated with isozymes of pI = 6.4 and 6.6. These isozymes were recognized by antibodies produced against pure horse and beef liver mitochondrial ALDHs. Both cytosolic and mitochondrial ALDHs were found in fetal liver as early as day 15 of gestation. The total activity for mitochondrial ALDH increased between day 15 and day 21 whereas that for cytosolic ALDHs remained relatively constant during development. It appeared that both cytosolic and mitochondrial ALDH were present by at least the third trimester and could afford the fetus some protection against the toxic action of endogenous or exogenous aldehydes. PMID- 2910310 TI - A novel form of cytochrome P-450 in beagle dogs. P-450-D3 is a low spin form of cytochrome P-450 but with catalytic and structural properties similar to P-450d. AB - A form of cytochrome P-450, P-450-D3, cross reactive with antibodies to rat P 450d was purified from liver microsomes of polychlorinated biphenyl (PCB)-treated female Beagle dogs to an electrophoretic homogeneity. Judging from the result of sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE), the molecular weight of P-450-D3 was estimated to be 54,000. The oxidized form of P 450-D3 showed a peak at 416 nm indicating that the cytochrome is mostly in a low spin state. The carbon monoxide bound reduced form of P-450-D3 showed a peak at 448 nm. In a reconstituted system, P-450-D3 catalyzed drug oxidations including benzphetamine and aminopyrine N-demethylations, 7-ethoxycoumarin and p propoxyaniline O-dealkylations, and aniline and benzo(a)pyrene hydroxylations. The rate of aniline hydroxylation catalyzed by P-450-D3 was similar to that catalyzed by P-450c which is a low spin form of cytochrome P-450 purified from liver microsomes of PCB-treated rats, whereas the catalytic activities of P-450 D3 for 7-ethoxycoumarin O-deethylation and benzo(a)pyrene hydroxylation were considerably lower than those of P-450c. The amino terminal portion of P-450-D3 was found to be highly similar to those of P-450d, human P3-450 and P3-450 when four amino acid deletions were tentatively inserted between fifth and sixth amino acids from the N-terminal, but not that of P-450c which is a low spin form of cytochrome P-448 purified from rat liver microsomes. These results indicate that Beagle dogs possess a low spin form of cytochrome P-450 with spectral properties similar to P-450c but with catalytic and structural properties similar to P-450d. PMID- 2910312 TI - Bilateral absence of the ulna in twins as a manifestation of the split hand- split foot deformity. AB - Bilateral absence of the ulna and ulnar rays in twin female infants are described as a manifestation of the split hand--split foot deformity (ectrodactyly). Family history revealed the father had a unilateral split hand. Given the wide variability of expression of this disorder and the availability of prenatal diagnosis, there is a need for obstetricians and pediatricians to recognize parents with this malformation and appreciate the potential for severely affected offspring. PMID- 2910311 TI - Increased hepatic retinal dehydrogenase activity after phenobarbital and ethanol administration. AB - Cytosolic retinal dehydrogenase (EC 1.2.1.36, retinal: NAD+ oxidoreductase) activity was measured by assessing the conversion of retinal to retinoic acid by HPLC. In vitro, acetaldehyde, chloral hydrate and disulfiram were found to be inhibitors, whereas 95% of the activity remained in the presence of cyanide or in the absence of oxygen. In rats, retinal dehydrogenase activity prevailed over that of retinal oxidase. By contrast, in deermice, 80% of retinal oxidation was due to the oxidase rather than the retinal dehydrogenase activity in a normal strain (ADH+) as well as in one lacking alcohol dehydrogenase (ADH-). In ADH- deermice, retinal oxidase activity was greater than in ADH+ animals. In vivo, in the rat, chronic ethanol administration resulted in a significant increase of the dehydrogenase activity in the liver, but not in other tissues. After phenobarbital administration, hepatic retinal dehydrogenase activity was increased 8-fold, but no extrahepatic induction was observed. Conversely, feeding rats with a diet devoid of the precursor for the substrate (retinal) by replacing retinyl acetate with an equivalent amount of retinoic acid resulted in decreased retinal dehydrogenase activity. Under conditions in which retinal dehydrogenase activity is rate-limiting for the metabolism of retinal to retinoic acid, its induction after phenobarbital or ethanol administration may contribute to hepatic vitamin A depletion. PMID- 2910313 TI - Maternal, cord, and neonatal carnitine correlations and lipid profiles of various birthweight infants. AB - The carnitine, acylcarnitine, and triglyceride concentrations were determined in the average for gestational age neonates of various birthweights and gestational ages and their corresponding maternal and umbilical cord plasma. Forty-two infants were divided into one of four groups based on birthweight: Group 1, less than 1000 gm; group II, 1001 to 1510 gm; group III, 1511 to 2500 gm; and group IV were term infants who served as the reference group. Results indicated that there was an overall decrease of total carnitine and nonesterified carnitine with advancing gestational age (r = -0.4418, p less than 0.01). Furthermore, there were three distinct phases of plasma carnitine concentrations from 24 weeks to term. The plasma carnitine profile of the neonates less than 1500 gm was strongly correlated (r = 0.73) to their maternal plasma carnitine profile and that of term neonate to their umbilical cord plasma. Acylcarnitine and triglycerides were not significantly correlated. PMID- 2910314 TI - Measures to enhance performance of an atraumatic cesarean section in prematurity. AB - Cesarean sections performed for the delivery of the premature infant are known to be prone to dangers to the fetus, primarily due to contraction of the incised but as yet undelivered uterus upon the fetus, which thus entraps it. Reported is our technique for performing a cesarean section in prematurity, describing two simple yet helpful measures-halothane administered to the mother and controlled entrance to the amniotic sac, after having completed the whole uterine incision without rupturing the membrances. These measures are designed to avoid or at least, it is hoped, to reduce the occurrence of the previously mentioned severe complication. PMID- 2910315 TI - Influence of the fetal scalp electrode stimulation test on fetal heart rate and body movements in quiet and active behavioral states during labor. AB - Thirty women were studied to examine the effect of fetal scalp stimulation on fetal heart rate (FHR) accelerations and gross body movements in quiet and active fetal behavioral states during the active phase of labor. Stimulation was performed by five consecutive tractions of the fetal scalp electrode. Fetal response in terms of fetal movements and FHR accelerations occurring within 15 seconds after stimulation was observed in all fetuses of the active state group. In the quiet state group 14 of 15 fetuses responded with body movements and in 12 fetuses FHR accelerations were observed. Subsequently, most of the fetuses returned to the quiet state. We suggest that a normal and healthy fetus is expected to respond to the fetal scalp electrode stimulation test even in the quiet behavioral state. PMID- 2910316 TI - Anesthesia for perinatal surgery. AB - A 30 year gravida 3 para 2002 woman presented at 28 weeks' gestation with polyhydramnios. Ultrasound revealed a single fetus with a large anterior neck mass. With halothane general anesthesia providing uterine relaxation and maintaining placental and umbilical blood flow, an otolaryngologist attempted to secure the airway. We discuss the rationale for our anesthetic management and suggest its use in similar situations in which surgical intervention may be required in the immediate perinatal period. PMID- 2910317 TI - Increased neonatal urinary ammonia: a marker for in utero caloric deprivation? AB - The decline in the urinary urea to ammonia ratio represents a simple measure of nutritional status in the adult. We examined the relationship of this ratio to nutrient-related fetal growth retardation. Levels of ammonia and urea nitrogen were measured in the first voided urine and cord blood from 15 term infants exhibiting a wide range of growth. Analysis by multiple regression with neonatal ponderal index as the primary dependent variable revealed a significant correlation between lowered ponderal index and decreased urinary urea and ammonia. The correlation was primarily a function of increasing ammonia levels, with no relationship between fetal leanness and urinary urea. Comparable cord artery and vein ammonia suggest that placental ammoniagenesis was not a major determinant of observed elevations in urinary ammonia. Confirmation of the striking correlation between increased urinary ammonia and lowered neonatal ponderal index may afford a simple test for the identification of nutrient related growth retardation. PMID- 2910318 TI - Diagnosis and management of susceptibility to malignant hyperthermia in pregnancy. AB - A case of susceptibility to malignant hyperthermia, diagnosed by muscle biopsy during the first trimester of pregnancy, is presented. Pertinent medical history that might raise this suspicion is reviewed. The pathophysiology of malignant hyperthermia is discussed. Recent reports documenting the placental transfer of dantrolene and complications associated with dantrolene administration during labor are described. The pharmacology of dantrolene sodium is presented. Guidelines regarding the management of labor and delivery in patients susceptible to malignant hyperthermia are outlined. Suggestions for counseling patients and their children with this syndrome are reviewed. PMID- 2910319 TI - Sepsis with Citrobacter diversus in sick newborns. AB - Citrobacter diversus has been increasingly recognized as a cause of life threatening neonatal meningitis with frequent abscess formation. This condition is associated with high mortality and extremely poor prognosis. We report our experience with C. diversus septicemia without meningitis in critically ill newborns. Thirteen patients with mean birthweight 1530 +/- 925 gm and mean gestational age 31.3 +/- 3.5 weeks were affected. They were compared with a group of infants affected by Escherichia coli sepsis, matched for weight, gestational age, and age at diagnosis. The groups did not differ in the incidence of perinatal complications, peripheral white blood cells, platelet count, and death rate. Hypotension was more frequently found in E. coli sepsis (p less than 0.05). All C. diversus isolates were resistant to gentamicin but sensitive to cephalosporins. C. diversus has become the most common nosocomial pathogen in our unit. Plasma profile analysis suggests that two different strains of C. diversus were involved in the outbreak reported here. Therapy for suspected C. diversus septicemia should include cephalosporins whenever resistance to aminoglycosides is demonstrated. PMID- 2910320 TI - Histologic examination of the placenta in the growth-retarded fetus. AB - This investigation was undertaken to determine whether histologic examination of the placenta contributed to a better understanding of the cause of intrauterine fetal growth retardation. Placentas were examined of 151 liveborn infants whose birthweights were in the lower 10th percentile for gestational age. One or more histologic aberrations were found in 139 (92%) cases, in contrast to one or more antenatal risk factors (primarily hypertension) in 77 (51%) cases or a gross placental abnormality (primarily abruption) in 46 (30%) cases. Compared with placentas belonging to appropriately sized fetuses, histologic signs of uteroplacental vascular insufficiency, chronic inflammation, and hemorrhagic endovasculitis were significantly more common in the study group. The primary histologic condition was supportive of prior clinical impressions in 61 (40%) cases, contradictory in 23 (15%) cases, or solely contributory to explaining the growth retardation in 55 (36%) cases. Placental histologic examination may clarify a cause for delayed fetal growth, especially after a normotensive pregnancy. PMID- 2910321 TI - Evaluation of a risk-scoring system for prediction of preterm labor. AB - A scoring system was used prospectively to screen 7329 patients for risk of preterm labor over a 6-year period. When 15.8% of patients (1156 of 7329) were scored as high risk, sensitivity was 42.4% (multiparas, 55.2%, nulliparas, 29.8%) and positive predictive value was 22.8%. The incidence of preterm labor increased with increasing risk score; gestational age at delivery was negatively correlated with risk score. Analysis of individual factors revealed that more than half were not of predictive value in the population under investigation. A simplification of the system, defining 12 of the factors as major (high risk) and six as minor (2 or more indicates high risk) yielded a high risk group of 14.1%, sensitivity of 41.0%, and positive predictive value of 24.6%. Thus, although risk scoring does predict a substantial proportion of patients with preterm labor, its sensitivity is less than ideal. No advantage was gained with a larger and more complex system. Planning for preterm birth prevention programs should include recognition of the limitations of risk scoring, consideration of simplified systems, and investigation of additional biochemical or biophysical screening methods. PMID- 2910322 TI - Micropenis and congenital adrenal hypoplasia. AB - Micropenis is often an early sign of congenital hypopituitarism. It has also been associated with congenital adrenal hypoplasia in infants with anencephaly and pituitary agenesis. This report is on two infants with micropenis and congenital adrenal hypoplasia. One presented with a similar clinical course and postmortem findings to previously reported cases of adrenal hypoplasia and pituitary agenesis. The other patient represents the first reported case of an infant with micropenis and congenital adrenal hypoplasia in the absence of pituitary agenesis. The histologic patterns of adrenal hypoplasia, as well as the etiologic and clinical implications of its association with micropenis, are discussed. PMID- 2910323 TI - Factors causing hyperkalemia in premature infants. AB - In order to clarify the causative factors of hyperkalemia in premature infants, 48 newborn infants less than 2000 gm birthweight were examined during the first 48 hours of life. They were divided into two groups: group A (n = 19), which had more than 7 mEq/liter of serum potassium level, was defined as a hyperkalemic group; group B (n = 29) had less than 6.9 mEq/liter of serum potassium level throughout this study period. In group A hyperkalemia occurred on the first day of life and continued throughout the study period. Five of group A infants had arrhythmia, one of whom died from cardiac arrest on the second day of life. Laboratory findings (serum creatinine, creatine phosphokinase, electrolytes, blood gas analysis, calorie balance, and renal function) were compared between the two groups. On the first day of life, serum creatinine and creatine phosphokinase concentrations were significantly elevated and calorie intake was decreased in group A when compared with group B. On the second day of life, calorie intake, urine volume, creatinine clearance, and base excess were significantly decreased in group A. A significant decrease was observed in the serum calcium level in group A on the second day of life when compared with admission data. These data suggest that neonatal hyperkalemia may occur in the sick newborn infants with renal dysfunction when combined with metabolic acidosis and catabolic state. PMID- 2910324 TI - Antihypertensive therapy in pregnancy directed by noninvasive hemodynamic monitoring. AB - Invasive and noninvasive investigations suggest that the hemodynamics of pregnant hypertensive patients are heterogeneous. Nineteen pregnant patients were evaluated before changes in antihypertensive therapy. Cardiac output was measured by Doppler technique. Blood pressure was measured by automated cuff. Systemic vascular resistance was calculated. Two distinct groups were identified on the basis of differences in cardiac output (p less than 0.0001) and systemic vascular resistance (p less than 0.0001). Those with high resistances were treated with hydralazine. A modest antihypertensive effect was achieved (-6.9 mmHg, p = 0.01), but systemic vascular resistance was dramatically reduced, (-534 dyne.sec.cm-5, p less than 0.0001) and was associated with a compensatory increase in cardiac output (2.0 liters/min, p less than 0.0001). Those with a high cardiac output were treated with atenolol. An antihypertensive effect was achieved, (-17.0 mm Hg, p = 0.008), which was associated with a reduction in cardiac output (-2.8 liters/min, p less than 0.0001). PMID- 2910325 TI - Delivery following cesarean section and perinatal mortality. AB - The perinatal mortality in 1498 patients with one or more previous cesarean section scars delivered between 1972 and 1982 was analyzed. Repeat elective cesarean section was performed in 654 (44%) patients and 844 (56%) were subjected to a "trial of scar." Successful vaginal delivery occurred in 702 (83%) patients and 142 (17%) had emergency repeat operations. There were 46 perinatal deaths, giving a perinatal mortality rate (PMR) of 30.3/1000. It was lowest in patients who electively had a cesarean section (10.6/1000). The corrected PMR was twice as high in the trial of scar group. The PMR for the overall hospital population (27,072 babies) during the study period was 22.5/1000. There were four perinatal deaths in association with dehiscence of the uterine scar. The PMR in trial of scar patients decreased from 40/1000 to less than 20/1000 without a major change in policy. Meanwhile the unit cesarean section rate increased from 5 to 10%, but the repeat section rate was consistent at around 38.5%. Regional analgesia was used in 192 patients, for repeat section in five and trial of scar in 187. Oxytocin was given to 546 (65%) patients. Scar rupture is considered the major contraindication to a trial of scar, but emphasis was not laid on the possible increased perinatal mortality with this procedure before the 1980s. In view of the improvement in the PMR and the added risk to the mother with cesarean delivery, we advocate a policy of trial of scar with informed consent in selected cases. PMID- 2910326 TI - Delivery following cesarean section and perinatal mortality. PMID- 2910327 TI - Use of continuous arteriovenous hemofiltration (CAVH) for renal failure in a neonate. PMID- 2910328 TI - [Short-latency somatosensory evoked potentials and auditory brainstem responses in children with brainstem lesions]. PMID- 2910329 TI - [Early morphological diagnosis of twitcher mice by the clipped tail]. PMID- 2910330 TI - [Prognostic evaluation of psychomotor development in infants by multimodal evoked potentials]. PMID- 2910331 TI - [Three cases of mucolipidosis III with significant differences in clinical pictures--reevaluation of the classification of mucolipidosis II and III]. PMID- 2910332 TI - [A case of neurenteric cyst diagnosed by magnetic resonance imaging]. PMID- 2910333 TI - [A case of partial ornithine transcarbamylase deficiency]. PMID- 2910334 TI - [A case of craniodiaphyseal dysplasia]. PMID- 2910335 TI - [A typical case of type I schizencephaly--MRI and clinical findings]. PMID- 2910336 TI - [Changes in cerebrospinal fluid neuron-specific enolase (NSE), S 100 protein and creatine kinase BB (CK-BB) levels in newborn infants with post hemorrhagic hydrocephalus]. PMID- 2910337 TI - [Intelligence and regional cerebral blood flow in children with Moyamoya disease]. PMID- 2910338 TI - You'll know you're a night nurse when.... PMID- 2910339 TI - CEU your jewish patient is dying.... AB - This article offers the nurse information needed for planning the care of Jewish patients and their families during the dying and mourning process - whether that patient is Orthodox, Conservative, or Reform. PMID- 2910340 TI - Now playing! Dilemma at Reality Windows, Inc. A burlesque on a critical issue in nursing. PMID- 2910341 TI - So you want to be promoted? AB - This article offers guidelines for the nurse who has promotion in mind and wants to maximize chances for goal attainment. PMID- 2910342 TI - Role modeling as a teaching strategy. AB - This article provides several ideas for using role modeling as a strategy for teaching clinical nursing, as well as suggestions for improving the effectiveness of this technique. Ideas were compiled from the literature and the author's experience in practice and teaching. PMID- 2910343 TI - How to survive the shift. PMID- 2910344 TI - Family care that works. PMID- 2910345 TI - A special breed. PMID- 2910346 TI - When you're the patient.... PMID- 2910347 TI - The N-acetylneuraminic acid content of five forms of human transferrin. AB - Five isoforms of human serum transferrin were separated by isoelectric focusing and their N-acetylneuraminic acid content was determined. The forms differed in isoelectric point by about 0.1 of a pH unit with the structural differences situated in the carbohydrate parts. Each form had one sialic acid molecule (NANA) less than the next most acidic form. GLC-MS showed that the most abundant form with isoelectric point 5.5 had two two-branched carbohydrate chains, each having the galactoses covered by terminal sialic acid. The form with isoelectric point 5.4 had one three-branched and one two-branched carbohydrate chain, and all branches terminated with a sialic acid residue. The form with isoelectric point 5.6 had a terminal galactose on one of its two two-branched carbohydrate chains. Comparison of the sialic acid content of the five transferrin forms and their carbohydrate structures showed that some of the forms expose terminal galactose without attracting the asialoglycoprotein receptors on hepatocytes. PMID- 2910348 TI - Proton nuclear magnetic resonance study of the histidine residues of pituitary bovine growth hormone. AB - The pKa value of histidines 20, 22 and 170 of pituitary bovine growth hormone (pbGH) and their C2H deuterium exchange rates have been determined by high resolution 1H-NMR spectroscopy. Partial assignment of these parameters indicate that His-170 is a surface residue with a half-life for deuterium exchange at the C2H position of approx. 36 h and a pKa value of 5.68 +/- 0.11. A reversible conformational change of pbGH has also been characterized in terms of the involvement of either histidines 20 or 22. At or near physiological pH values, one of these residues is expelled from a buried, hydrophobic position to become fully solvent-exposed. The disparity in pKa values between histidines 20 and 22 (4.67 +/- 0.20 and 5.94 +/- 0.10, in some combination) has been shown by computer modeling, to be compatible with these residues residing in an alpha-helical region of the protein. PMID- 2910349 TI - Rat liver S-adenosylhomocysteinase. Spectrophotometric study of coenzyme binding. AB - Rat liver S-adenosylhomocysteinase, a homotetramer, was resolved by treatment with acid ammonium sulfate into apoenzyme and NAD. The apoenzyme thus prepared retained a tetrameric structure but differed in the mobility on nondenaturing polyacrylamide gel electrophoresis. The inactive apoenzyme was reactivated upon incubation with NAD. The restoration of activity paralleled with the tight binding of NAD to apoenzyme, and full activity was obtained when 4 mol of NAD were bound per mol of apoenzyme. The kinetics of reconstitution were apparently biphasic and suggest the existence of two conformers in a slow equilibrium, one of which binds the coenzyme rapidly while the other does so very slowly, if at all. In addition to NAD, apoadenosylhomocysteinase tightly bound nicotinamide hypoxanthine dinucleotide, 3-acetylpyridine adenine dinucleotide and nicotinic acid-adenine dinucleotide. NADP was not bound. Catalytic activity was found only with the enzyme reconstituted with NAD or nicotinamide hypoxanthine dinucleotide. The spectral change observed on interaction of apoadenosylhomocysteinase with NAD was similar to those seen with adenine nucleotides, and was largely approximated by the addition of dioxane to aqueous solutions of adenine nucleotides. By comparison of the difference spectra, it is suggested that the adenine portion of the coenzyme is bound in the hydrophobic pocket of the protein, and that the binding is accompanied by perturbation of tryptophan residue of the protein. PMID- 2910350 TI - Time-resolved fluorescence studies on NADH bound to mitochondrial malate dehydrogenase. AB - Time-resolved fluorescence studies on the emission of NADH bound to porcine heart mitochondrial malate dehydrogenase [S)-malate:NAD+ oxidoreductase, EC 1.1.1.37), in the presence and absence of saturating levels of hydroxymalonate, were carried out. The lifetime of NADH bound in the ternary complex was determined to be 9.5 ns compared to 1.74 ns as reported in the literature. Steady-state and dynamic polarization data indicated a Debye rotational relaxation time in the range of 106-109 ns for the dimeric enzyme. This value is significantly larger than that calculated for a spherical protein and is consistent with the asymmetric dimer found by crystallographic studies. PMID- 2910351 TI - The amino acid sequence of S-antigen: N-terminus and uveitogenic peptides. AB - Bovine S-antigen purified in the presence of proteinase inhibitors contained a protein (30%) having an acetylated N-terminus (Ac-Met-Lys-Ala-Asn-Lys-Pro-Ala...) and a protein (70%) having an N-terminus unblocked but four residues less (Lys Pro-Ala-Pro-Asn-His-Val-Ile-Phe...). Sequencing studies showed that uveitogenic peptides produced by chymotryptic digestion of S-antigen derived from the C terminal half of the protein. PMID- 2910352 TI - Proliferation and maturation of human erythroid progenitors in liquid culture. AB - Hemopoiesis is studied in vitro mainly in semisolid culture, where hemopoietic progenitors develop into discrete colonies. We describe a liquid culture system that supports the proliferation and maturation of human erythroid progenitors. We seeded mononuclear cells from the peripheral blood (PB) of patients with beta thalassemia in liquid medium in the presence of conditioned medium from human bladder carcinoma cells. Seven days later, RBCs, normoblasts, granulocytes, and monocytes disappeared, and the number of lymphocytes dropped considerably. In contrast, erythroid colony-forming cells increased fourfold to tenfold. The next step entailed the removal of colony-stimulating factor (CSF) and CSF-secreting cells, the exclusion of macrophages by harvesting nonadherent cells, and the lysis of T lymphocytes by treatment with monoclonal rat antihuman lymphocyte antibodies (CAMPATH-1) and complement. Reculture of the remaining cells in liquid medium supplemented with recombinant erythropoietin (EPO) resulted in the exclusive development of erythroid cells, with myeloid cells reduced to less than 2%. Stainable hemoglobin (Hb) appeared on day 3, with over 85% of the population containing hemoglobin by day 11 and the cell number increasing from 0.2 X 10(6) to 3 X 10(6) mL. By permitting the manipulation of culture conditions and components and increasing the cell yield, the liquid system may facilitate quantitative analysis of growth kinetics as well as biochemical and immunologic characterization of the developing erythroid cell. PMID- 2910353 TI - Dual role of fibronectin in hematopoietic differentiation. AB - The adhesive glycoprotein fibronectin provides anchorage for fibroblasts and hematopoietic progenitor cells in vitro. Fibronectin also demonstrates growth factor activity for fibroblasts; however, there is no available information regarding its role as a hematopoietic growth factor. To distinguish growth factor activity of fibronectin from its anchorage activity for hematopoietic progenitors, we assessed the ability of purified human plasma fibronectin to promote human bone marrow erythroid, granulocyte-macrophage (GM) and mixed granulocyte-erythroid-macrophage-megakaryocyte (GEMM) colony formation in liquid suspension, methylcellulose, and fibrin clots under serum-free conditions. Addition of fibronectin to methylcellulose cultures, or to cultures formed in fibrin clots, using fibrinogen depleted of fibronectin by preadsorption over gelatin-Sepharose and clotted with thrombin, resulted in up to a twofold enhancement of proliferation of erythroid burst-forming units (BFU-E), erythroid colony-forming units (CFU-E), and CFU-GEMM. This effect was concentration dependent up to a fibronectin supplement of 100 micrograms/mL. By contrast, CFU GM proliferation was not affected by the addition of fibronectin to the cultures. Fibronectin-adherent marrow cells overlaid with liquid medium formed both early and late-appearing erythroid colonies, whereas similarly cultured plastic adherent marrow cells did not. Erythroid colony formation was observed in cultures of fibronectin-adherent marrow cells overlaid with methylcellulose but not in cultures of plastic-adherent marrow cells under the same conditions. Finally, the erythroid growth-promoting activity of fibronectin was inhibited by arginyl-glycyl-aspartyl-serine (RGDS), a tetrapeptide that competitively blocks the interaction of fibronectin with its receptor. We conclude that fibronectin plays a dual role in hematopoiesis: providing (a) anchorage for erythroid and primitive progenitors, and (b) as a proliferative stimulus for these hematopoietic cells. Both activities may be mediated by the cell adhesion domain of the molecule. PMID- 2910354 TI - Stimulation of erythropoietin gene transcription during hypoxia and cobalt exposure. AB - Erythropoietin, a plasma glycoprotein produced primarily by the kidney, is a growth and differentiation factor for erythroid progenitor cells. Production of renal erythropoietin is regulated by modulation of mRNA levels in response to changes in tissue oxygenation. Exposure to cobalt, a nonphysiologic stimulus for erythropoietin production, also acts by inducing mRNA accumulation. To determine whether variations in erythropoietin mRNA levels result from enhanced transcription of the erythropoietin gene, in vitro transcription reactions were performed using isolated rat kidney cell nuclei. Quantitation of specific nuclear RNAs labeled during in vitro transcription revealed active erythropoietin gene transcription in kidney nuclei from anemic-hypoxic and cobalt-treated animals while erythropoietin transcriptional activity was undetectable in normal kidney nuclei. Time course studies showed that stimulation of transcription begins between two and four hours following cobalt treatment and parallels the kinetics of mRNA and plasma erythropoietin accumulation. These results indicate that tissue hypoxia and cobalt exposure specifically enhance erythropoietin gene expression. This increase in erythropoietin production is regulated at least in part at the level of gene transcription. PMID- 2910355 TI - Alpha-tocopherol, an effective inhibitor of platelet adhesion. AB - Platelet adhesiveness was tested ex vivo in a group of six normal individuals receiving varying doses of alpha-tocopherol. Adhesion to glass slides coated with fibronectin, collagen, fibrinogen, or plasma proteins was studied by perfusing platelet-rich plasma through a flow chamber that allowed time- and space-resolved observations of platelet adhesion. Platelet adherence was measured in an area of parallel flow lines and low shear rate under standardized conditions before and after dietary supplementation with vitamin E at doses of 200 and 400 IU/d. Platelet adherence differed in magnitude depending on the adhesive surface. There was a distinct preference of platelets to adhere to sites that had been previously occupied. A remarkable decrease in platelet adherence was observed after vitamin E supplementation. The average decrease in adhesion after 2 weeks of 200 IU vitamin E was 75%. After 2 weeks of 400 IU vitamin E, platelet adhesion was reduced by 82%. The inhibitory activity of alpha-tocopherol was dose dependent and correlated well with the increase in alpha-tocopherol concentration in platelets after supplementation. Scanning electron microscopy revealed a striking decrease of pseudopodium formation in alpha-tocopherol-enriched platelets. Our results suggest that vitamin E may also be an effective antiadhesive agent in vivo. PMID- 2910356 TI - Hepatitis B virus DNA in the serum of Sardinian blood donors negative for the hepatitis B surface antigen. AB - The high endemicity of hepatitis B virus (HBV) infection and liver disease in Sardinia led us to assess the occurrence of HBV DNA in 1,411 sera of two selected groups of hepatitis B surface antigen (HBsAg)-negative blood donors: 793 with abnormal serum alanine aminotransferase (ALT) and 618 with normal serum ALT values (determined during routine testing of their blood donation). HBV DNA sequences were detected by dot-blot hybridization in 68 of 793 subjects (9%) with abnormal ALT but only in three of 618 subjects (0.5%) with normal ALT. HBV-core antibody (anti-HBc) was detected in 338 of 793 subjects (43%) with abnormal ALT as well as in 125 of 618 subjects (20.2%) with normal ALT. Among the 71 subjects positive for serum HBV DNA, 22 (31%) were positive for anti-HBc, while 49 (69%) were negative for all serologic markers of HBV infection. Thus, a high frequency of anti-HBc in apparently healthy HBsAg-negative individuals and a high prevalence of serum HBV DNA in the absence of immunologic markers of HBV infection suggest the existence of genetic variants of HBV that may be responsible for some of the presumed NANB hepatitis encountered in Sardinia and possibly other areas of high endemicity for HBV. PMID- 2910357 TI - Abnormalities of cytoplasmic Ca2+ in platelets from patients with uremia. AB - Uremic patients have a hemorrhagic tendency, often associated with prolonged bleeding times and decreased platelet function in vitro. Whether these defects result from abnormalities in plasma factors affecting platelet activity, platelet surface receptors, intracellular platelet mediators, or other aspects of platelet behavior is unknown. To examine the possibility that the abnormality in platelet function may result from aberrations in Ca2+ homeostasis, blood was obtained from 29 patients with severe uremia. The platelets were washed, loaded with the Ca2+ sensitive probes indo-1 and aequorin, gel-filtered, and resuspended in either plasma or buffer. Of the 29 patients, seven had template bleeding times prolonged to 11 minutes or more, but platelet aggregation in plasma was not consistently impaired in these patients. However, in aequorin-loaded platelets from the patients with long bleeding times, the highest elevation of cytoplasmic calcium [( Ca2+]i) in response to the Ca2+ ionophore A23187, arachidonate, adenosine diphosphate (ADP), or epinephrine was lower than that seen in platelets from both uremic patients with less prolonged bleeding times and normal volunteers. The reduced [Ca2+]i response was associated with decreased aggregation of gel filtered platelets suspended in buffer. Suspending washed aequorin-loaded uremic platelets in normal plasma for 20 minutes did not reverse the decreased agonist induced rise in [Ca2+]i; platelets from a normal donor resuspended in uremic plasma aggregated and produced a normal increase in [Ca2+]i in response to agonists. We conclude that the platelet defect seen in some patients with uremia is associated with a decreased rise in platelet [Ca2+]i after stimulation and that this is a manifestation of an intrinsic platelet defect. PMID- 2910358 TI - Heparin binds to human monocytes and modulates their procoagulant activities and secretory phenotypes. Effects of histidine-rich glycoprotein. AB - The binding of heparin to human monocytes and the monocytoid cell line U937 was characterized. Heparin binding was rapid, specific, saturable, and reversible. There was a single class of heparin binding sites, with an apparent dissociation constant of 0.19 mumol/L and 1.9 x 10(6) sites per cell. The binding was not dependent on the anticoagulant property of heparin. Analysis of surface-iodinated cell lysates by heparin affinity chromatography revealed a major 120 Kd cell surface heparin-binding protein. Histidine-rich glycoprotein, a potent heparin antagonist found in human plasma and platelets, decreased the affinity of heparin for cell binding. Cell surface bound heparin was functionally active and markedly accelerated the inactivation of thrombin by antithrombin III. Heparin induced the release of two monocyte secretory proteins of 160 and 17 Kd. Our study supports the thesis that heparin and related glycosaminoglycans interact with monocytes and macrophages, as well as endothelial cells and smooth muscle cells, and play an important and complex role in blood vessel wall biology. PMID- 2910359 TI - Histidine-rich glycoprotein does not interfere with interactions between antithrombin III and heparin-like compounds on vascular endothelial cells. AB - The role of histidine-rich glycoprotein in controlling heparin-like compounds on the endothelial cell surface is still unclear. The effects of this heparin neutralizing protein on the interaction between antithrombin III and cultured porcine aortic endothelial cells were examined. Displacement of 125I-labeled antithrombin III specifically bound to endothelial cells by unlabeled histidine rich glycoprotein was much less potent than that by unlabeled antithrombin III. One hundred-fold molar excess of histidine-rich glycoprotein displaced specific 125I-antithrombin III binding only by 20%. Furthermore, the endothelial cell mediated acceleration of thrombin inactivation by antithrombin III was diminished by protamine sulfate, but was not affected by histidine-rich glycoprotein even at a histidine-rich glycoprotein/antithrombin III molar ratio of approximately 7:1. These data indicate that histidine-rich glycoprotein does not interfere with the interaction of endothelial cell heparin-like compounds with antithrombin III. Thus, it may not play an important role in the modulation of anticoagulant activity of endothelial cells in vivo, suggesting that the commonly accepted view of the probable function of this protein is erroneous. PMID- 2910360 TI - Isolation of Reed-Sternberg cells from lymph nodes of Hodgkin's disease patients. AB - This study describes a simple and relatively rapid method of purifying Reed Sternberg (R-S) cells and their morphologic variants from the lymph nodes of patients affected by Hodgkin's disease. Our initial studies defined the optimal procedure for a quantitative disaggregation of Hodgkin's lymph nodes and the densities of R-S cells in several donors. These preliminary steps were helpful in the development of strategies for selectively concentrating R-S cells by density gradient centrifugation. We layered a single-cell suspension over Percoll of appropriate density, centrifuged these samples for 15 minutes, and collected a fraction enriched in R-S cells. Most of the R-S cells were distributed between densities of 1.060 and 1.072, with a peak at approximately 1.066 g/mL. R-S cells are denser than many mononuclear cells present in the lymph nodes of Hodgkin's patients and lighter than reactive cells such as eosinophils, mast cells, and neutrophils. However, the ranges of densities of these cell types overlap, making purification of R-S cells by isopyknic centrifugation impossible. Nevertheless, when this enriched fraction is further processed by velocity sedimentation in order to take advantage of the larger size of R-S cells as compared with all other cells, a substantial purification is achieved. We used three different velocity-sedimentation chambers to find the optimal conditions for obtaining the highest purity with a high final yield. The cells isolated by this method are viable, appear to be morphologically normal, and have been further characterized biologically. PMID- 2910361 TI - Vitamin D metabolite-mediated hypercalcemia and hypercalciuria patients with AIDS and non-AIDS-associated lymphoma. AB - Fifteen patients with lymphoma and hypercalcemia (greater than or equal to 11.0 mg/dL) were identified by screening the serum chemistry profile obtained from patients upon admission to the Los Angeles County/USC Medical Center. Seven of the 15 (47%) possessed a frankly elevated serum concentration of 1,25 dihydroxyvitamin D [1,25-(OH)2-D]. An additional patient with severe hypercalcemia (16.2 mg/dL) had a serum 1,25-(OH)2-D concentration in the midnormal range, not a suppressed value. To examine the potential existence of hypercalciuria in absence of overt hypercalcemia, prospective screening of 23 normocalcemic patients with lymphoma was undertaken. Four of the 23 patients (17%) had increased fractional urinary calcium excretion rates (0.35 +/- 0.3 mg calcium/100 mL glomerular filtrate [GF], mean +/- SE; normal, less than 0.16 mg/100 mL GF); two of the hypercalciuric patients had a frankly elevated serum 1,25-(OH)2-D concentration. Of the 19 hypercalcemic/hypercalciuric lymphoma patients identified, none had an elevated serum immunoreactive parathyroid hormone concentration. Fourteen of the 19 hypercalcemic/hypercalciuric patients (74%) suffered from B-cell neoplasms, three had Hodgkin's lymphoma, and two had adult T-cell leukemia/lymphoma. All hypercalcemic/hypercalciuric patients had widespread disease (stage III or IV). Six patients, four with hypercalcemia and two with hypercalciuria, had acquired immunodeficiency syndrome (AIDS). These data suggest that the deregulated synthesis of a 1,25-(OH)2-D-like metabolite is a common cause of hypercalcemia and hypercalciuria in patients with lymphoma including patients with AIDS-associated tumors. PMID- 2910362 TI - In vivo cell growth and pharmacologic determinants of clinical response in acute myelogenous leukemia. AB - A predictable increase in the proliferative rate of malignant cells remaining after initial cytoreduction in vivo forms the rationale for timed sequential therapy (TST) with 1-B-D-arabinofuranosylcytosine (ara-C) for adult acute myelogenous leukemia (AML). The relationship between in vivo leukemic cell growth, intracellular ara-C metabolism, and clinical response to ara-C-containing TST was evaluated by comparing AML marrow cell growth kinetic and biochemical pharmacologic determinants obtained before therapy (day 0) and at the predicted peak of in vivo postdrug residual tumor proliferation (day 8). Serial measurements of DNA synthesis and net intracellular ara-C metabolism demonstrated marked increases in both determinants in day 8 residual tumor when compared with the pretreatment cells for newly diagnosed adults achieving complete remission but not for TST-refractory patients. The interrelationship of AML cell proliferation and biochemical pharmacology together quantitate cytotoxicity measured by both achievement and duration of remission and serve to predict eventual clinical outcome in response to TST with ara-C where both growth and favorable pharmacokinetics are intrinsic to the success of the drug schedule. PMID- 2910363 TI - Protooncogene expression and the clinical characteristics of acute nonlymphocytic leukemia: A Leukemia Intergroup pilot study. AB - Northern blot analysis was used to assess the level of expression of five protooncogenes and histone H3 in the bone marrow cells of patients with acute nonlymphocytic leukemia (ANLL). The relationship between the level of gene expression and the clinical characteristics of the disease and response to therapy was studied. The levels of expression of c-myc and c-myb are weakly correlated and are unrelated to French-American-British (FAB) type of ANLL. The levels of expression of c-fms, c-fes, and c-fos are highly correlated with each other and are highest in leukemia with a monocytic component (c-fms v FAB = .71, c-fes v FAB = .75). High levels of c-myc expression are associated with a high probability of not responding to remission induction therapy (P = .004). The converse is true for c-fms expression levels. High levels of expression of c-myc or c-myb are associated with short remissions (P = .059 and .065, respectively), perhaps because they are associated with a high capacity for leukemic cell self renewal and/or an inability of leukemic cells to differentiate in response to chemotherapy. PMID- 2910364 TI - Prognostic impact of cytogenetic abnormalities in patients with de novo acute nonlymphocytic leukemia. AB - Detailed cytogenetic analyses were performed on specimens from 198 patients with de novo acute nonlymphocytic leukemia (ANLL), including high-resolution banding studies in 79 patients. One hundred ninety-two patients received induction therapy with daunorubicin and cytosine arabinoside (Ara-C) with an overall complete response rate (CR) of 63%. Responding patients received repetitive cycles of Ara-C-based intensification therapy. Clonal abnormalities were detected in 69% of the patients with specimens adequate for cytogenetic analysis. Certain cytogenetic changes were closely associated with French-American-British (FAB) morphology, age, and outcome: t(8;21) (closely associated with FAB M2), t(15;17) (associated with FAB M3), and abn 16q22 (associated with FAB M4EOS) tended to occur in younger patients and were associated with favorable outcomes in terms of both CR rate and long-term disease-free survival. In contrast, 19% of patients who had -5/5q- and or -7/7q- and seven patients with trisomy 8 were older, had a poor prognosis, and usually failed to achieve remission (CR) because of chemotherapy-resistant leukemia. The adverse effect on CR rate and duration in this group of patients was independent of age, and there was no association with particular morphologic subtypes. These data suggest that cytogenetic findings should influence future therapeutic choices. In particular, patients with abnormalities associated with poor responses may be considered for investigational approaches and may also provide insights into mechanisms of drug resistance. PMID- 2910365 TI - Immunophenotype-karyotype associations in human acute lymphoblastic leukemia. AB - The present study is a detailed analysis of the cytogenetic features of leukemic cells from 104 immunologically classified acute lymphoblastic leukemia (ALL) (78 B lineage and 26 T lineage) cases. Clonal chromosomal abnormalities were found in marrow blasts from 77 of 104 (74%) cases. Hyperdiploidy was much more frequent in B-lineage ALL cases, whereas normal diploidy was more common in T-lineage ALL cases. Fifty-nine of 104 cases (46 of 78 B-lineage ALL and 13 of 26 T-lineage ALL cases) had structural chromosomal abnormalities. Structural abnormalities involving 2p11, 7p13, 7p22, proximal q arm of 7 (7q11 or 7q22), 11q23-24, and translocations involving 12p11-13 appeared to be B-lineage specific. By comparison, structural abnormalities involving 7p15, 7q32, and 14q11 displayed T lineage specificity. Structural abnormalities involving 9p22-p23 or 14q32, del (6)(q21-q23), del (12)(p11-p13), and the Philadelphia chromosome were found in B lineage as well as T-lineage ALL cases. This study expands the current knowledge about immunophenotype-karyotype associations in ALL. PMID- 2910367 TI - Jaw involvement in Burkitt's lymphoma. PMID- 2910368 TI - Age as a prognostic factor in multiple myeloma. PMID- 2910366 TI - Inactivation of Friend erythroleukemia virus and Friend virus-transformed cells by merocyanine 540-mediated photosensitization. AB - The Friend virus complex was used as a model to study the effects of merocyanine 540 (MC 540)-mediated photosensitization on enveloped viruses. Simultaneous exposure to the lipophilic dye MC 540 and white light inactivated cell-free virus, cell-associated virus, and virus-transformed cells. When used under experimental conditions that are known to preserve most mature blood cells, at least some coagulation factors, and a significant portion of the pluripotent hematopoietic stem cell compartment, MC 540-mediated photosensitization reduced virus titers by greater than or equal to 4 log and the concentration of in vitro clonogenic erythroleukemia cells by greater than or equal to 5 log. Animals that received a single intravenous injection of photosensitized virus were resistant to a subsequent challenge with live virus. High sensitivity to MC 540-mediated photosensitization appears to be a property that is shared by other enveloped viruses. Thus, photosensitization mediated by MC 540 may be of benefit in the sterilization of blood products (in particular, cellular products), the production of vaccines, and selected areas of antiviral therapy. PMID- 2910369 TI - High-dose intravenous methylprednisolone for immune thrombocytopenic purpura. PMID- 2910370 TI - Suppressive effects in vivo of purified recombinant human H-subunit (acidic) ferritin on murine myelopoiesis. AB - Purified recombinant human heavy-chain (acidic) ferritin (rHF) was assessed in vivo in mice for effects on the proliferation (percentage of cells in S-phase) and absolute numbers of granulocyte-macrophage (CFU-GM), erythroid (BFU-E), and multipotential (CFU-GEMM) progenitor cells in the femur and spleen and on the nucleated cells in the marrow, spleen, and blood. rHF significantly decreased cycling rates and absolute numbers of marrow and splenic hematopoietic progenitors and marrow and blood nucleated cellularity. These effects were apparent in BDF1, C3H/Hej and DBA/2 mice and were dose dependent, time related, and reversible. Suppressive effects were noted within three hours for progenitor cell cycling, within 24 hours for progenitor cell numbers, and within 48 hours for circulating neutrophils. Additionally, hematopoietic progenitor cells in DBA/2 mice infected with the polycythemia-inducing strain of the Friend virus complex (FVC-P) were insensitive to the in vivo administration of rHF. These studies demonstrate activity of rHF in vivo on myelopoiesis of normal but not FVC P-infected mice. Since rHF suppresses hematopoietic progenitor cell proliferation from normal donors in vitro and from normal mice in vitro and in vivo but does not suppress progenitor cells from patients with leukemia in vitro or from mice with FVC-P-infection in vitro or in vivo, rHF may be useful as a candidate adjunct molecule for the protection of normal hematopoietic progenitor cells during chemotherapy. PMID- 2910372 TI - Nurses unified against RCT threat. PMID- 2910371 TI - Survival of recombinant erythropoietin in the circulation: the role of carbohydrates. AB - Recombinant human erythropoietin produced in transfected Chinese hamster ovary cells is glycosylated much the same way as the erythropoietin present in human urine. To determine the role of carbohydrates in the stability of recombinant human erythropoietin in vivo, [125I]-labeled recombinant erythropoietin was intravenously infused into rats. The erythropoietin was slowly cleared from the blood with a half-life of approximately two hours. Asialoerythropoietin, which was produced by treatment of recombinant human erythropoietin with sialidase, was found to be cleared rapidly from circulation within ten minutes. These data suggest that the galactose binding protein of hepatic cells is involved in the clearance of asialoerythropoietin. Erythropoietin also contains N-glycans with a few N-acetyllactosamine repeats, which can be enriched by tomato lectin affinity chromatography. The lectin-bound fraction was cleared to a larger extent than was the unfractionated erythropoietin, while the component that did not bind the lectin was found to be stable in the circulation. Authentic N-acetyllactosamine repeats (polylactosaminoglycans) prepared from erythrocytes were similarly rapidly cleared from the circulation to the liver, and this clearance was inhibitable with asialo-alpha 1-acid glycoprotein. These results suggest that (a) the sialic acid of the recombinant erythropoietin is necessary for this glycoprotein hormone to circulate stably and (b) glycoproteins with more than three lactosaminyl repeat units may be cleared by the galactose binding protein of hepatocytes. PMID- 2910373 TI - The challenge of putting new knowledge into practice. PMID- 2910374 TI - Fate of the gallbladder with cholelithiasis after endoscopic sphincterotomy for choledocholithiasis. AB - Endoscopic sphincterotomy is the treatment of choice for choledocholithiasis after cholecystectomy. Its role has been expanded to treat choledocholithiasis in patients with gallbladders still in place. The authors report their experience with endoscopic sphincterotomy, with emphasis on the safety of the procedure, in high-operative-risk patients with choledocholithiasis and gallbladder in situ. Stones were successfully removed in 72 of 75 patients (96%); 1 required an emergency operation and 2 an elective one. Complications included bleeding, pancreatitis and cholangitis; there were no associated deaths. Follow-up of 54 of the patients, who had associated cholelithiasis at the time of endoscopic sphincterotomy, showed that 14 died of causes unrelated to the biliary tract. Of the others, 14 underwent cholecystectomy for failure of endoscopic sphincterotomy (2), acute cholecystitis (4) or persistent biliary tract symptoms (8). The other 26 patients were well after a mean follow-up of 30.4 months; 1 had mild biliary tract symptoms. Ultrasonography in 16 of the 26 patients showed persistent cholelithiasis in 12. Life-table analysis revealed a 15% probability of acute cholecystitis within 5 years of endoscopic sphincterotomy. PMID- 2910375 TI - Acute scrotal pain in children: prospective study of diagnosis and management. AB - Forty-eight boys were assessed for an acutely painful scrotum. Thirty-six (75%) of them underwent radionuclide scanning of the scrotum; the average age of this group was 11 years. The scan revealed epididymitis in 19 cases, spermatic cord torsion in 9, appendix testis torsion in 7 and acute hernia-hydrocele in 1. The diagnosis was confirmed at operation in all nine cases of spermatic cord torsion. Boys who had epididymitis received antibiotics only; all were available for short term follow-up, and 16 were also assessed at a mean of 6 months after infection. Only one boy had testicular atrophy; he had undergone repair of an inguinal hernia, which could not be ruled out as a cause. Bacteriuric epididymitis occurred in three boys; two had known predisposing genitourinary anomalies, the third had no abnormalities. Boys who had nonbacteriuric epididymitis were investigated by renal and pelvic ultrasonography or voiding cystourethrography; no important abnormalities were detected. This prospective study indicates that radionuclide scanning can reliably differentiate spermatic cord torsion from other acute scrotal disease. PMID- 2910376 TI - An adrenalin rush. PMID- 2910377 TI - Diurnal variation in admission to hospital of women in labour. AB - In women having spontaneous labour or premature rupture of the membranes there is a marked diurnal variation in times of admission to hospital. Analysis of 4755 nulliparous women with single pregnancies in cephalic presentation at term, indicated that they presented in labour or with premature rupture of the membranes nearly twice as frequently during the night as during the evening. The peak hours for delivery were late morning and afternoon. The authors discuss previously published reports of similar findings and of a diurnal variation in maternal hormone levels in humans and experimental animals. The potential clinical importance of this phenomenon is considered. PMID- 2910378 TI - Surgical treatment of post-traumatic kyphosis: a report of 16 cases. AB - Thoracic and lumbar spine fractures may lead to symptomatic progressive kyphosis for which surgery remains a controversial treatment. Sixteen patients with kyphosis were treated surgically at the Sacre-Coeur Hospital in Montreal between 1979 and 1985. The mean follow-up was 38 months. Initially, treatment of the fractures varied. On average the post-traumatic kyphosis was surgically corrected 34 months later. The corrective procedure consisted of staged anterior and posterior fusion with instrumentation (six patients), posterior fusion with instrumentation (five), staged anterior fusion, posterior osteotomy and fusion with instrumentation (four), posterior osteotomy and fusion with Harrington instrumentation (one). Anterior decompression was also performed in 5 of the 10 patients who had anterior fusion. There was no major perioperative complication. Pain was relieved in 13 patients and 9 of 11 had substantial neurologic improvement. Two patients had nonunion of posterior grafts, but these united after revision. The mean loss of correction in the early postoperative period was 3.5 degrees. The authors conclude that surgical treatment of post-traumatic symptomatic progressive kyphosis is effective and safe. PMID- 2910379 TI - Perioperative chemotherapy for primary sarcoma of bone. AB - Preoperative chemotherapy for primary osteosarcoma has usually been accompanied by a prolonged delay between withdrawal before operation and resumption after. This is because animal studies showed impaired wound healing associated with perioperative chemotherapy. Clinical studies, however, have not shown this to be the case. The authors describe their experience in eight patients who had osteosarcoma and Ewing's sarcoma of the extremities and received one to three cycles of chemotherapy preoperatively. Chemotherapy consisted of Adriamycin, cis platinum and vincristine. Definitive surgery on the primary tumour was done 1 to 4 days after the last dose. Amputation was performed on seven patients and tumour resection for limb salvage on one. No wound healing or infectious complications were encountered. The ensuing course of chemotherapy was not delayed by the surgical procedure. The authors conclude that it is feasible to combine neoadjuvant chemotherapy and early surgery in the management of high-grade primary bone sarcoma. PMID- 2910380 TI - Above-knee femoropopliteal reconstruction with polytetrafluoroethylene: a good alternative to saphenous vein bypass. AB - Over 6 1/2 years, 64 femoropopliteal bypasses were done on 55 patients, using polytetrafluoroethylene (PTFE). The PTFE was chosen because previous surgery or small diameter prohibited the use of saphenous vein. The distal anastomoses were always placed above the knee. Patency rates were 92% at 1 month, 76% at 1 year, 72% at 2 years and 59% at 3 years, and then reached a plateau of 55% at 4 years. When autogenous vein is not available, PTFE is the material of choice for femoropopliteal reconstruction. The results compare favourably with those using saphenous vein in an above-knee situation. PMID- 2910381 TI - A plea for standard methods of reporting studies on lower extremity ischemia. PMID- 2910382 TI - Adrenal myelolipomatous nodules mimicking adrenal neoplasms: report of three cases. AB - The authors describe three cases of adrenal myelolipoma. In the first two, unilateral adrenal masses, assumed to represent adrenal neoplasms, were found during urologic examination; the correct diagnosis was made by frozen-section examination during operation. The third case involved bilateral adrenal lesions diagnosed at autopsy in a patient suspected to have metastatic cancer. Histologic, immunohistochemical and electron microscopic studies revealed polyclonal lesions composed of hematopoietic cells and fat cells. Radiologic recognition and fine-needle biopsy of these lesions are important to avoid unnecessary surgery in asymptomatic cases. Since the lesions cannot be regarded as true neoplasms, the authors suggest that the name myelolipoma should be replaced by the term myelolipomatous nodule. PMID- 2910383 TI - Complications and functional results after limb-salvage surgery and radiotherapy for difficult mesenchymal neoplasms: a prospective analysis. AB - Wide resection with adjuvant radiotherapy is generally accepted as the optimal treatment for patients with extremity soft-tissue sarcomas. However, there is a subset of patients with "difficult" tumours who sustain such marked loss of function from limb-salvage procedures that amputation might offer a superior functional alternative. To evaluate this issue, the authors prospectively designated 19 of 52 patients registered in Toronto's Princess Margaret Hospital Prospective Sarcoma Database in 1986 as "difficult" cases, on the basis of tumour size and anatomical location. Complications and functional results of wide resection and adjuvant radiotherapy were documented. The most frequent complication was related to wound healing (8 of 19 patients). Functional analysis at 1 year follow-up demonstrated that all 19 patients had results superior to those that would be expected with amputation. PMID- 2910384 TI - Primary omental torsion. PMID- 2910385 TI - Immediate thrombosis of carotid endarterectomy. PMID- 2910386 TI - Anteromedial (perineal) dislocation of the hip: a case report. AB - Anteromedial (perineal) dislocation of the hip is rare. The authors describe the case of a 13-year-old girl whose femoral head was dislocated into the vagina as a result of a motor vehicle accident. The hip could not be reduced by traction but was pushed through the vagina with moderate ease. When the patient was placed in the lithotomy position, the hip redislocated and further reduction was required. The vagina and soft tissues were repaired and the hip joint was irrigated and closed over a drain. Antibiotics were given for 10 days. The girl recovered completely. PMID- 2910387 TI - Potential danger. PMID- 2910388 TI - Prenatal care: a comparative evaluation of nurse-midwives and family physicians. PMID- 2910389 TI - AIDS testing: mathematical models. PMID- 2910390 TI - Junk mail. PMID- 2910391 TI - Dermatophytosis in institutions for the elderly. PMID- 2910392 TI - Simple solution to snoring. PMID- 2910393 TI - Should Canadians support NAMDA or MASA? PMID- 2910394 TI - Ensuring a heart-healthy pilot population [correction]. PMID- 2910395 TI - Human immunodeficiency virus type 2. PMID- 2910396 TI - The decision not to resuscitate: talking with patients and families. PMID- 2910397 TI - Pediatric manpower in Canada: a cross-country survey. AB - Health care costs and government cutbacks in Canadian training posts have caused concerns about physician manpower. To determine the present pediatric manpower situation a cross-country survey was undertaken of all pediatricians and their practice patterns. Of the 2060 recipients of a questionnaire 5% were found to not be pediatricians. Of the remaining 1960, 69% returned a completed questionnaire. Overall, 70% of the pediatricians were men, although among those less than 35 years of age 49% were women. Across Canada 37% of the pediatricians practised primary care, 25% secondary care and 38% tertiary care. There were wide regional differences in practice patterns, with large numbers of primary care pediatricians in Winnipeg, Toronto, Ottawa and the province of Quebec; few pediatricians in the Maritimes and the remainder of western Canada practised primary care. Non-Canadian graduates accounted for 33% of the pediatricians and represented a considerable proportion of tertiary care pediatricians. Cutbacks in numbers of pediatric training positions and restrictions on immigration of foreign pediatricians may lead to unexpected deficiencies in the availability of some types of pediatric practitioners, especially those in tertiary care. PMID- 2910398 TI - The value of pulmonary function tests in the management of acute asthma. AB - We examined the influence of the forced expiratory volume in 1 second (FEV1) on the decision to admit or discharge patients who present with acute bronchospasm due to asthma and the ability of the FEV1 to predict the need for admission or the likelihood of relapse after discharge. The FEV1 was recorded at presentation before treatment and immediately after a decision to admit or discharge had been made. Of the 96 patients 10.4% were admitted, 10.4% were discharged but suffered a relapse, and 79.2% were discharged and did not suffer a relapse. The FEV1 had a low positive predictive value (47%) for admission or relapse when it was 0.7 L/min or less at presentation and 2.1 L/min or less before discharge or admission. The FEV1 did not alter the decision to admit or discharge in 97% of the cases. We believe that the FEV1 fails to identify patients who should be admitted or those who will likely suffer a relapse; however, patients with a final FEV1 greater than 2.4 L/min may be discharged with confidence. PMID- 2910399 TI - Rates and outcome of pregnancies achieved in the first 4 years of an in-vitro fertilization program. AB - Between Feb. 1, 1984, and Dec. 31, 1987, 578 couples were treated in the in-vitro fertilization (IVF) program at University Hospital, London, Ont. The 160 confirmed pregnancies resulted in 86 deliveries and the birth of 108 babies. There were 20 spontaneous abortions, 12 ectopic pregnancies, 11 presumptive pregnancies, 4 neonatal deaths and 1 stillbirth. At the time of writing, 41 pregnancies of 20 weeks' gestation or more were in progress. Except for a high cesarean section rate the obstetric outcome of pregnancies achieved with IVF does not appear to be different from that expected for a group of infertile couples treated with conventional therapies. The pregnancy rates varied according to the denominator used. PMID- 2910400 TI - Hypercholesterolemia. PMID- 2910401 TI - There are fewer doctors sitting in new Parliament. PMID- 2910402 TI - Care in the air: quality of airline medical kits varies widely. PMID- 2910403 TI - It's a sad day for medicine in Ontario. PMID- 2910404 TI - After rocky start, plans for international AIDS conference move ahead. PMID- 2910405 TI - CMA will launch major strategic planning exercise, board decides. PMID- 2910406 TI - Canada's doctors--who they are and what they do: lessons from the CMA's 1986 manpower survey. PMID- 2910407 TI - Hurricane Gilbert devastated Carribean medical school. PMID- 2910408 TI - Queen's aims to become the little school that could. Interview by David Helwig. PMID- 2910409 TI - Biologic and cytogenetic characteristics of leukemia in infants. AB - Clinical features, leukemic cell characterization, chromosomal findings, and treatment outcome were analyzed in a retrospective study of 30 cases with acute leukemia of infancy, 24 infants with acute lymphoblastic leukemia (ALL), and six cases with acute nonlymphoblastic leukemia (ANLL). Extensive bulky disease with organomegaly, central nervous system (CNS), and skin involvement were prominent features at diagnosis with a higher frequency in ANLL as compared to ALL. Four of six ANLL patients were classified as monocytic or myelomonocytic. In the ALL group nine of 24 (36%) were non-L1 morphology and six of 17 (33%) were common ALL antigen (CALLA) negative, the majority of them (five of six) were included in the non-L1 group. Immunophenotyping revealed four cases with early B-cell (three patients: Ia+B4+, and one patient: Ia+) and two cases with T-cell. Mixed lineage leukemia was found in five infants. Heavy chain immunoglobulin gene rearrangement was present in six cases tested, two CALLA+, two with Ia+B4+, and two were undifferentiated mixed lineage leukemia. Chromosomal aberrations were detected in ten of 18 patients, mostly in ANLL and CALLA negative ALL. Translocations were detected in six patients, involving 4q21-23 and 11q23 in three and two cases, respectively. The probability of five-year DFS were 27% for the whole group. The worst prognosis was observed in infants younger than 6 months of age, in whom the leukemia cell characteristics was compatible with stem cell: ANLL, very early pre B, or undifferentiated mixed type. The chromosomal aberrations found in all cases included translocation with the seemingly nonrandom breakpoints at 4q21 and 11q23, and breakpoints that corresponded to known fragile sites. This finding may be suggestive of an underlying genetic predisposition associated with the poor prognosis of leukemia of infancy. PMID- 2910410 TI - Cytogenetic findings and prognosis in neuroblastoma with emphasis on marker chromosome 1. AB - The relationship between cytogenetic findings and prognosis in 51 pediatric patients with neuroblastoma is described. Patients were classified into the following four groups based on karyotypic findings: (1) near diploidy, 42 to 47 chromosomes (n = 11); (2) hyperdiploidy, 50 to 56 chromosomes (n = 4); (3) near triploidy, 60 to 77 chromosomes (n = 33); and (4) hypotetraploidy, 80 to 83 chromosomes (n = 3). Patients with near diploid or hypotetraploid karyotypes also had several structural abnormalities including marker chromosome 1, with or without double minutes (DM) or homogeneously staining regions (HSR). Most of these patients were 1 year of age or older and had advanced tumors. The patients who were in the hyperdiploid or near triploid category had few structural abnormalities; all of them, except one, were younger than 1 year of age, had localized tumors, and are long-term, disease-free survivors. Kaplan-Meier analysis of survival rates disclosed a significant difference favoring the latter group (P less than 0.001). N-myc gene amplification was found in five patients of the former group but in no patients of the latter group. The presence or absence of DM or HSR in the former group had no statistically demonstrable effect on survival. However, the presence of marker chromosome 1 appears to indicate a poor prognosis. Five patients with Stage IV-S disease had near triploid abnormalities similar to findings in patients with localized tumors. We propose that localized and Stage IV-S neuroblastomas can be classified as one disease category, and that patients with near diploid or hypotetraploid karyotypes are clinically distinct from those having hyperdiploid or near triploid karyotypes. We consider that chromosomal pattern is a more influential prognostic factor than age, disease stage, or N-myc gene amplification. PMID- 2910411 TI - Value of venous catheterization and calcitonin studies in the treatment and management of clinically inapparent medullary thyroid carcinoma. AB - Seventeen patients with medullary thyroid carcinoma (MTC) underwent venous catheterization (VC) for sampling and serum calcitonin (CT) assay. The VC was performed either after an initial treatment in order to detect cervical recurrences and metastases (16 patients) or to prove abnormal CT thyroid secretion before any treatment (one patient). In 16 of the 32 tumoral localizations suspected by VC (50%), a tumoral focus was proven. For selective/peripheral CT gradient value superior to 2.50, 12 localizations of 12 (100%) were proven and for CT gradient value between 1.50 and 2.50, four localizations of 15 (26.6%) were proven. In six patients with exclusive cervical MTC secreting sites, treatment induced a total remission in two cases (12%) and improved in four cases (23%). The authors conclude that VC has a real value to localize MTC secreting sites. A total remission or an improvement can be obtained after treatment when VC detects exclusive cervical tumors. PMID- 2910412 TI - Selection of hormone-responsive advanced breast cancer with a cytoplasmic estrogen receptor assay. Analysis of 100 cases. AB - One hundred women with advanced breast cancer were treated with endocrine therapy alone and the clinical response was correlated with the estrogen receptor status of the tumor as determined by a fluorescent histochemical assay designed to estimate the percentage of cancer cells with high cytoplasmic estrogen binding activity. Using clinical response rates as the standards for measurement, this histochemical method showed an 84% sensitivity, a 74% specificity, a 76% positive predictive value and an 82% negative predictive value. These results indicate that the histochemical assay may serve as a supplementary means to identify hormone-responsive mammary carcinomas and as a research tool to study the biology of this group of tumors. PMID- 2910413 TI - The percentage of aneuploid cells is significantly correlated with survival in accurately staged patients with stage 1 resected squamous cell lung cancer and long-term follow up. AB - Previous studies have shown that ploidy is an important prognostic determinant in lung cancer, but in those studies followup was restricted to three years, while patients with Stage 1, 2 and 3 disease and with different histological subtypes were included. Theoretically, these factors could have influenced the findings, especially since aneuploidy strongly correlated with the stage of disease. Because of this, tumor ploidy was studied in surgically resected stage 1 (T1/2, N0M0) squamous cell lung cancer patients with a minimal followup of 6 years. All patients were accurately staged by mediastinal lymph node mapping. Fifty-two from a group of 1539 patients with lung cancer diagnosed between 1980 and 1986 inclusive, fulfilled these criteria. Of these tumors, 23 (44%) were diploid with a 6-year survival of 53% and 29 (56%) were aneuploid with a 6-year survival of 48%. Although diploidy tended to be associated with local relapse of the tumor and aneuploidy with distant metastases, the difference was not significant and neither showed a survival advantage. However, within the aneuploid tumors, there was a significant correlation between the percentage of aneuploid cells and survival, defined as event-free or time to death. Seventeen patients with a percentage of more than 10 had a worse outcome (12 died, 6 years survival 35%), than to the other 12 patients with less than 10% aneuploid cells (2 died, 6-year survival 78%) (Mantel-Cox = 6.04, P = 0.01). This implies that in patients with accurately staged and histologically proven Stage 1 squamous cell lung cancer and long-term follow up, DNA content classified as diploid and aneuploid is not a prognostic factor for survival, but the percentage of aneuploid tumor cells is correlated with the prognosis. PMID- 2910414 TI - Atypical cysts and carcinomas of the kidneys in the phacomatoses. A quantitative DNA study using static and flow cytometry. AB - Reported are the pathologic features of atypical cysts and/or renal cell carcinomas found in the kidneys of four patients having either tuberous sclerosis or Hippel-Lindau disease. In addition, cellular DNA contents of the cells lining the atypical cysts and comprising the carcinomas were quantitated using both static and flow cytometric techniques. These studies showed that cysts lined by atypical epithelial cells are frequently present in renal parenchyma adjacent to the renal carcinomas, and that the cytologic features of atypical cells lining the cysts were essentially the same as the cytologic features found in the adjacent well-differentiated, renal cell carcinomas. DNA quantitative studies revealed that both the renal cell carcinomas and the atypical cyst lining cells had the same DNA indices and were essentially DNA euploid. In this patient group these findings are consistent with the hypothesis that the atypical cyst lining cells evolve into the renal cell carcinomas; however, they do not prove this proposed but likely sequence. PMID- 2910415 TI - Early liver metastases in patients with medullary carcinoma of the thyroid gland. AB - In 13 patients who had been thyroidectomized for medullary carcinoma (MCT), basal and pentagastrin-stimulated immunoreactive calcitonin (iCT) concentrations were measured in a peripheral vein and concomitantly in hepatic veins as well as in the superior and inferior caval veins. The basal concentrations of iCT in serum from the antecubital vein ranged from normal values (less than 0.50 micrograms/1) to grossly elevated (greater than 100 micrograms/1). Intravenous pentagastrin injections (0.5 micrograms/kg) stimulated transiently calcitonin secretion in all patients and peak concentrations occurred in peripheral venous blood and in the inferior caval vein after 3 to 5 minutes. In all patients peak iCT values in the hepatic vein occurred at 1 to 2 minutes and were much higher than in samples taken from other veins. Only three patients showed metastases to liver as judged by conventional clinical and laboratory examinations. Two patients with nonthyroid, malignant disease did not show an increase in serum iCT concentration of hepatic veins. The authors conclude that MCT may spread early to the liver. The presence of liver metastases is an important prognostic factor in patient evaluation and can be demonstrated by measuring iCT in hepatic veins before and during pentagastrin stimulation. PMID- 2910416 TI - Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases. AB - Two of the most important prognostic indicators for breast cancer are tumor size and extent of axillary lymph node involvement. Data on 24,740 cases recorded in the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute were used to evaluate the breast cancer survival experience in a representative sample of women from the United States. Actuarial (life table) methods were used to investigate the 5-year relative survival rates in cases with known operative/pathologic axillary lymph node status and primary tumor diameter. Survival rates varied from 45.5% for tumor diameters equal to or greater than 5 cm with positive axillary nodes to 96.3% for tumors less than 2 cm and with no involved nodes. The relation between tumor size and lymph node status was investigated in detail. Tumor diameter and lymph node status were found to act as independent but additive prognostic indicators. As tumor size increased, survival decreased regardless of lymph node status; and as lymph node involvement increased, survival status also decreased regardless of tumor size. A linear relation was found between tumor diameter and the percent of cases with positive lymph node involvement. The results of our analyses suggest that disease progression to distant sites does not occur exclusively via the axillary lymph nodes, but rather that lymph node status serves as an indicator of the tumor's ability to spread. PMID- 2910417 TI - Malignant melanoma with metastasis to adenocarcinoma of the prostate. AB - Tumor-to-tumor metastases are uncommon despite the fact that the presence of two or more malignancies in a single patient is not a rare occurrence. The most frequent donor tumors are the lung, prostate, and thyroid gland, whereas renal cell carcinoma is by far the most common recipient. In this report we describe a patient dying of metastatic malignant melanoma and locally advanced prostate cancer in which the melanoma metastasized to the prostatic adenocarcinoma. The prostatic primary was well differentiated and stained positively with prostate specific antigen and prostatic acid phosphatase, whereas the melanoma contained abundant melanin pigment and stained positively for S-100 protein. This is the second reported instance of prostatic carcinoma as the recipient in a case of tumor-to-tumor metastases and the first in the English language literature. PMID- 2910418 TI - Hyperthermic isolated regional perfusion in the treatment of extremity melanoma in children and adolescents. AB - From 1973 to 1982 six children and eight adolescents with extremity melanomas were treated by local excision and adjuvant hyperthermic isolated regional perfusion with Melphalan (L-phenylalanine mustard, manufactured by Burroughs Wellcome Company, Research Triangle Park, NC). The median Breslow thickness of the melanomas was 2.7 mm (range, 1 to 15 mm). According to the M.D. Anderson classification, nine patients were in Stage IA and five were in Stage IIIB. The median follow-up period was approximately 10 years. Distant metastases developed in three patients (21%) (one patient was in Stage IA [11%] and two patients were in Stage IIIB [40%]). In two cases the development of distant metastases was preceded by local recurrence (14%). The 5-year survival rate was 93%. The 10-year survival rate was 81%. The high survival rate, even for patients with unfavorably thick melanomas, seems to be attributable to isolated regional perfusion. PMID- 2910419 TI - Sexual dysfunction and treatment for early stage cervical cancer. AB - Assessment of sexual frequency, function, and behavior, as well as martial happiness and psychological distress was performed for 61 women with early stage, invasive cervical cancer at the time of diagnosis. Cancer treatment was radical hysterectomy alone for 26 women and radiotherapy with or without surgery for 37. Followups took place at 6 and 12 months after cancer therapy. Women's sexual satisfaction, capacity for orgasm, and frequency of masturbation remained stable, whereas frequency of sexual activity with a partner and range of sexual practices decreased significantly by one year. Women who received irradiation with or without surgery resembled women who underwent radical hysterectomy alone at 6 months. By one year, however, the radiotherapy group had developed dyspareunia, which was reflected in gynecologist ratings at pelvic examination. The women receiving radiotherapy also had more problems with sexual desire and arousal, and were less likely to resume several daily life activities. Cancer treatment modality was not related to marital happiness or stability, however. PMID- 2910420 TI - Long-term vocational adjustment of cancer patients diagnosed during adolescence. AB - Long-term vocational achievements of 40 survivors of cancer diagnosed during adolescence were examined and compared with 40 healthy sex-matched and age matched controls. Patients' ages at diagnosis ranged from 13 to 19 years (mean, 16.15). Study subjects had survived cancer for over 5 years and were on no cancer therapy. Assessment measures included the Rand General Well-Being Scale, the Rand Functional Limitations and Physical Abilities Batteries, and a semistructured interview. The relation of physical disability and limitations caused by cancer to patients' achievements also was evaluated. Although cancer patients, on the average, were more concerned about their health and reported lower general spirits than controls, no differences were found between control and study groups with regard to overall general well-being. More cancer patients than controls reported that their health limited their ability to engage in vigorous activities. A greater functional deficit was found among unemployed than employed cancer patients. Employers and co-workers often were aware of the patient's diagnosis (85% and 67%, respectively). Cancer patients reported disease-related discrimination in hiring (7.4%), induction into the military (66.7%), and obtaining health, life, and disability insurance (31.5%). There was no significant relationship between health status and employment. Nevertheless, cancer patients had a higher average income than controls. Sixty-four percent of patients believed that changes in certain physical features of the workplace were necessary to facilitate readjustment to the job. Despite the disabilities experienced by cancer patients and generally negative public attitudes, long-term survivors have a good outlook on life and are competitive members of the workplace and society. PMID- 2910421 TI - A comparison of two regimens for high-risk acute lymphocytic leukemia in childhood. A Pediatric Oncology Group Study. AB - Four hundred thirty patients with high-risk acute lymphoid leukemia were entered on the acute leukemia in childhood protocol (AlinC 12) of the Pediatric Division of the Southwest Oncology Group (now the Pediatric Oncology Group) between 1976 and 1979. This study was a prospective randomized comparison of two regimens that had as their primary differences: (1) an intensification period with Cytoxan (cyclophosphamide) and asparaginase after induction; (2) a period of intravenous methotrexate before initiating maintenance; and (3) in the regimen that had those two additions, triple-drug chemoprophylaxis of the central nervous system (CNS) using methotrexate, hydrocortisone, and cytosine arabinoside as compared to cranial irradiation and intrathecal methotrexate. All patients received vincristine and prednisone induction, 6-mercaptopurine and methotrexate maintenance, and vincristine and prednisone pulse intensification. There was no significant difference in the rate of bone marrow relapse. However, overall disease-free survival favored the arm with intensification and chemoprophylaxis because of a lesser incidence of extramedullary relapse. Thus, for treatment 1 versus treatment 3 the two-sided P values were for overall disease-free survival 0.16; bone marrow relapses 0.13; all CNS relapses 0.04; and all extramedullary disease relapses 0.013. It is concluded that intensification as delivered in this protocol protects against testicular relapse and that chemoprophylaxis is adequate prophylaxis against isolated CNS relapse. PMID- 2910422 TI - A randomized study of inpatient versus outpatient continuous infusion chemotherapy for patients with locally advanced head and neck cancer. AB - This study was designed to evaluate the safety, reliability, and patient acceptance of outpatient continuous intravenous infusion (CVI) chemotherapy. Twenty-two patients with locally advanced head and neck cancer received induction chemotherapy with methotrexate, cisplatin and a 5-day CVI of 5-fluorouracil (5 FU). Patients were randomized to receive the 5-FU portion of cycle 1 either by a standard inpatient CVI chemotherapy delivery device (standard pump) or by the Infusor (Baxter Healthcare Corporation, Deerfield, IL), a portable chemotherapy delivery system that provides a constant flow of drug over a period of 24 hours. For cycle 2, patients crossed over to the alternative drug delivery method. Patients receiving chemotherapy via the Infusor could choose to be either inpatients or outpatients. Daily plasma concentrations of 5-FU were determined during the first two cycles of chemotherapy. There was no significant difference in the mean steady state plasma 5-FU levels achieved with either drug delivery method (329.7 +/- 95.8 ng/ml for infusor cycles vs. 352.8 +/- 114.9 ng/ml for standard pump cycles). Clinical toxicities consisted primarily of mucositis for both methods of drug delivery. Eight patients declined to receive CVI chemotherapy as outpatients citing as reasons fear of malfunction of the device, inconvenience of the frequent clinic visits necessitated by daily monitoring of plasma 5-FU concentrations, and restrictions in daily home activities. Eleven patients underwent CVI chemotherapy via Infusor as outpatients. All reported outpatient CVI chemotherapy as convenient and effective and, when eligible, chose it again in subsequent cycles. A comparison of estimated costs revealed reductions in daily costs of +366.00 (+2,200.00 per cycle) for outpatient chemotherapy. Outpatient CVI chemotherapy is a reliable drug delivery method that was accepted by a majority of patients in this study. These factors may help to establish outpatient CVI chemotherapy as a viable alternative to hospitalization. PMID- 2910423 TI - Decreased cardiac toxicity of doxorubicin administered by continuous intravenous infusion in combination chemotherapy for metastatic breast carcinoma. AB - Two hundred and seventy-four consecutive patients with measurable metastatic breast cancer, without prior exposure to cytotoxic agents were treated with tamoxifen, 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC). The initial 133 patients received doxorubicin by bolus IV administration and for the next group of 141 patients doxorubicin was administered via a central venous catheter over a 48-hour (79 patients) or 96-hour (62 patients) continuous infusion schedule. Patients treated with bolus doxorubicin had this agent discontinued usually when 450 mg/m2 were reached; for patients in the infusion group treatment was continued until evidence of progressive disease or clinical or subclinical cardiac dysfunction developed. The complete remission rate was 21% the partial remission rate, 59%. There were no differences in response rate, response duration, or survival duration between groups of patients treated with doxorubicin by bolus, 48-hour or 96-hour infusion FAC. The incidence of moderate and severe nausea and vomiting was lower in the group of patients treated with infusion FAC as compared to bolus FAC (P less than 0.001); however, the incidence of mucositis was higher in the infusion group than in the bolus group (P less than 0.001). Doxorubicin administered by continuous infusion schedules was less cardiotoxic than when administered by bolus, as shown by a greater than 75% decrease in the frequency of clinical congestive heart failure at cumulative dosages greater than or equal to 450 mg/m2 (P = 0.004). Doxorubicin administered as a 48-hour or 96-hour continuous IV infusion is safer, and better tolerated than doxorubicin administered by bolus. PMID- 2910424 TI - A combination of intraarterial chemotherapy, preoperative and postoperative radiotherapy, and surgery as limb-saving treatment of primarily unresectable high grade soft tissue sarcomas of the extremities. AB - The localization and size of a high-grade soft tissue sarcoma of an extremity are generally the limiting factor in limb-saving surgery. Since 1982 nine patients with a high-grade soft tissue sarcoma of an extremity, which usually requires amputation, have been treated by intraarterial chemotherapy, preoperative and postoperative radiotherapy, and surgery. The limb was saved in eight patients (89%). During a median follow-up of 24 months (mean follow-up 32 months, range 12 to 64 months) one local recurrence and four distant metastases were diagnosed. Three patients developed complications due to the intraarterial chemotherapy, a motor and sensory neuropathy of the sciatic nerve was diagnosed in one patient, and two patients developed a flexion contracture of the knee. The results obtained in this small series show that the combination of intraarterial doxorubicin, preoperative and postoperative radiotherapy, and surgery is feasible in limb-saving treatment of primarily "unresectable" high-grade soft tissue sarcomas of the extremities without increasing the risk of a local recurrence. PMID- 2910425 TI - Effect of cumulative courses of intraarterial cis-diamminedichloroplatin-II on the primary tumor in osteosarcoma. AB - Preoperative chemotherapy with intraarterial cis-diamminedichloroplatin-II (CDP) and mannitol diuresis was administered to the primary tumor in 42 patients with osteosarcoma. The dose was 150 mg/m2 and more than 90% of the infusions were administered during a 2-week period. On occasion this period was extended to 3 weeks because of temporary renal insufficiency or logistical circumstances. Definitive surgical specimens were prepared by means of an arteriogram-directed plane of dissection with mapping and random sections. Histologically, tumor destruction was evaluated in terms of necrosis, inflammatory response, and fibrovascular regeneration. Quantification of the percent of tumor necrosis was as follows: less than 40% (consistent with spontaneous necrosis and/or no chemotherapy effect); 40% to 60% (possible chemotherapy effect); 60% to 90% (chemotherapy effect--partial response); and 90% to 100% (complete response). Therapeutic efficacy also was correlated with the number of CDP courses (one to three, four to five, and six to seven) and tumor subtype. Significant therapeutic effect (greater than 60% destruction) was observed with four or more CDP courses (one of nine tumors [one to three courses] versus 26 of 33 tumors [four to seven courses] [P = 0.01]). More than 60% of the tumor destruction was observed in the following subtypes: osteoblastic (22 of 28), fibroblastic (three of six), and telangiectatic (two of five). These data demonstrate that four or more courses of intraarterial CDP are required to achieve optimum effects and that osteoblastic osteosarcoma is highly responsive. PMID- 2910426 TI - Mediastinoscopy incision site metastasis. Implications for radiotherapeutic treatment. AB - The risk of iatrogenic tumor seeding from mediastinoscopy is low. Reported is a case of mediastinoscopy incision site metastasis treated palliatively. The implications for radiotherapy treatment are discussed. PMID- 2910427 TI - Dose-response and failure pattern for bulky or barrel-shaped stage IB cervical cancer treated by combined photon irradiation and extrafascial hysterectomy. AB - From 1975 to 1987, 80 patients with bulky or barrel-shaped Stage IB cervical cancer were treated with preoperative irradiation and Cs-137 intracavitary implant therapy, before a planned extrafascial abdominal hysterectomy, using a consistent treatment policy. Of the hysterectomy specimens obtained, 37% were positive histologically at 89 +/- 2.3 days after the start of radiotherapy and at 4 to 6 weeks after the completion of radiation therapy. Sixty-three percent were negative after a total external and internal cervix irradiation dose of 9642 cGy at point T. The average point A dose contributed by intracavitary therapy was 2104 cGy. The survival rate at 5 years was 84%: At 10 years the survival rate was 78%. The failure pattern was analyzed for patients who had positive and negative specimens. The patients with positive specimens failed pelvically or pelvically and distantly. Patients with negative specimens failed in extrapelvic or distant metastatic sites. Preoperative radiotherapy led to excellent local and pelvic control of tumor, and the failures became predominantly distant metastases. The combined radiosurgical therapy was tolerated well and allowed surgical staging of disease. This permitted earlier and selective consideration of adjunctive therapy (i.e., paraaortic irradiation, chemotherapy, or chemoradiotherapy). The dose response data give insight into the effects of photon radiotherapy on bulky or barrel Stage IB cervical cancers and correlate histologic status with failure pattern, outcome, and long-term survival. PMID- 2910428 TI - Preoperative cutaneous lymphoscintigraphy in malignant melanoma. AB - To identify the regional lymph node basins cutaneous lymphoscintigraphy with technetium 99m rhenium sulfide colloid (99mTc-ReS) was performed in 45 patients and with technetium 99m antimony sulfide colloid (99mTc-Sb2S3) in seven patients after excisional biopsy of the primary tumor. All patients had skin tumors located in the face or neck or on the trunk with 47 cases of cutaneous malignant melanoma and 5 cases of benign or premalignant lesions. In 48 patients the scintiscans 1 hour after perilesional injection of the tracer colloid clearly showed the lymphatic drainage patterns from the tumor sites, of them 25 patients demonstrated unidirectional drainage, whereas the remaining 23 patients had multidirectional drainage to two or three lymph node groups. There were technical difficulties in performing the examinations in four patients. The authors recommend cutaneous lymphoscintigraphy as a safe, simple and reliable technique for mapping the lymphatic drainage preoperatively in patients with Stage I cutaneous malignant melanoma of axial localization. PMID- 2910429 TI - Pyrimidine nucleotide synthesis is more extensive in poorly differentiated than in well-differentiated human gastric carcinoma. AB - In tissues obtained from patients undergoing gastrectomy, the activities of 12 enzymes involved in pyrimidine nucleotide synthesis: cytidine triphosphate (CTP) synthetase, deoxycytidine monophosphate (dCMP) deaminase, thymidine monophosphate (dTMP) kinase, uridine (Urd), deoxycytidine (dCyd) and thymidine (dThd) kinases, Urd, deoxyuridine (dUrd) and dThd phosphorylases, cytidine (Cyd) and dCyd deaminases, and DNA polymerase were examined in the eight-well-differentiated and 12 poorly differentiated gastric cancer tissues and the ten normal tissues. These cases were clinically advanced and serosal invasions were evident. Activities of these enzymes were higher in the poorly differentiated tissues than the well differentiated type and in the normal tissues. Significant differences were noted between the poorly differentiated and well-differentiated types, in dTMP kinase (P less than 0.02), dThd kinase (P less than 0.05), dThd phosphorylase (P less than 0.01), and DNA polymerase (P less than 0.05). The authors' findings show that the level of pyrimidine nucleotide synthesis, in both de novo and salvage pathways, is higher in the poorly differentiated gastric cancer tissues than in the well-differentiated type and suggest that antitumor drugs have an increased susceptibility in cases of poorly differentiated gastric carcinoma. PMID- 2910430 TI - Conservative treatment of distal rectal cancer by local excision. AB - From 1954 through 1982, 57 patients with invasive, distal rectal cancer had a full-thickness local excision with curative intent. Prognostic criteria and need for further treatment were based on the histopathologic results of the operative specimen. The overall 5-year survival rate was 83.4%. The rectal cancer-specific mortality rate was 10.5%. None of the 27 patients without adverse prognostic factors died from rectal cancer, and for this group local excision alone was sufficient treatment. The only single factors associated with an adverse outcome were mucinous characteristics and full-thickness invasion. Ulceration alone and penetration into the muscularis propria alone were not adverse factors. In the presence of multiple adverse prognostic factors, mucinous characteristics or full thickness penetration, local excision was inadequate treatment and an abdominal perineal resection was necessary. PMID- 2910431 TI - High-dose cyclophosphamide in the treatment of refractory lymphomas and solid tumor malignancies. AB - Twenty-two patients with refractory solid tumors or lymphoma were treated with a single course of high-dose cyclophosphamide (120 mg/kg intravenously [IV] over 2 days) whereas three patients received two courses each. Marrow infusion was not used. In the 22 courses evaluable for tumor response there were 14 responses (64%) of which 11 were partial responses (PR) (50%) and three complete responses (CR) (14%). In the 12 evaluable courses given in patients with lymphoid malignancies a partial response was obtained in seven (58%) and complete response in two (17%) for an overall response rate of 75%. The median duration of response was short: 2 months (range, 1-12 months). Twenty-seven courses were evaluable for toxicity. All patients had nadir polymorphonuclear leukocytes counts less than 500/mm3 with median time to recovery to a level greater than 500/mm3 of 9 days (range, 6-21 days). The median nadir platelet count was 30,000/mm3. One patient had prolonged thrombocytopenia of 225 days. There were two toxic deaths related to leukopenia, one secondary to Pneumocystis carinii pneumonia, and the second from probable sepsis and cholecystitis. Nineteen patients had previously received cyclophosphamide in standard doses. In the patients with lymphoid malignancies who had previously received cyclophosphamide, 22% achieved a CR with an overall response rate of 78%. High-dose cyclophosphamide may be given with acceptable toxicity in heavily pretreated patients. Given the short response duration in patients with progressive disease, the optimal results of such high-dose cyclophosphamide may be achieved when it is employed earlier in the natural history of the disease in conjunction with other alkylators, or as consolidation therapy. PMID- 2910432 TI - Characterization of a human ovarian carcinoma cell line with estrogen and progesterone receptors. AB - The potential significant therapeutic and prognostic roles for the sex steroid receptors in ovarian cancer are recognized. The authors present in detail the biochemical, morphologic, cytogenetic, and growth characteristics of an ovarian carcinoma cell line, BG-1, which has functional estrogen and progesterone receptors (23 and 300 fmol/mg protein, respectively) in clinically significant levels. In particular, BG-1 has a DNA index of 1.14, a stable karyotype with specific translocations, and produces and secretes CA 125 into the media. PMID- 2910433 TI - Differences in prognostic factors between leukemia and lymphoma type of adult T cell leukemia. AB - Prognostic factors affecting the survival of adult T-cell leukemia (ATL) patients were analyzed in three groups: total cases, leukemia type cases, and lymphoma type cases. Factors found to be important overall, i.e. for total cases, were leukocyte count, ATL cell ratio in the peripheral blood, serum calcium levels and lactate dehydrogenase (LDH) level. Of those, LDH level proved not significant when evaluated separately for leukemia type or lymphoma type cases. Leukocyte count and ATL cell ratio were significant in leukemia type patients, whereas it was serum calcium level that was significant in lymphoma type; there were mutually exclusive sets of factors for the two groups. Thus, prognostic factors for ATL patients should be considered separately for each type of the disease. PMID- 2910434 TI - Acute nonlymphocytic leukemias of childhood. Inter-observer variability and problems in the use of the FAB classification. AB - The French-American-British (FAB) classification system and some recent modifications were applied to 486 children with a diagnosis of acute nonlymphocytic leukemia (ANLL) to determine the distribution of the subtypes in children, to document the extent of inter-observer variation in assigning subtypes, and to examine the reasons for the differences. The distribution of FAB subtypes of childhood ANLL was similar to that reported for adults. In the initial year of the study, the inter-observer concurrence between the institutional diagnosis and the reviewing pathologists was 50%, but in the more recent years, concurrence between institutions and the review pathologist has approached 80%, averaging around 73% for the entire study. Many problems remain to be solved with this classification system, including the imprecision in wording, the subjectiveness of the interpretation, errors due to the random distribution of cells, and the current lack of evidence that certain FAB subtypes, such as M1 and M2, differ significantly in terms of biological behavior and prognosis. PMID- 2910435 TI - Pineocytomas. AB - Six cases of histologically proven pineocytoma are reported. The diagnosis was established by surgery in five cases and at autopsy in one. All patients received focal radiation therapy (4500 to 5400 cGy). Two patients had local recurrences at 1 and 48 months and subsequently died of tumor. A third patient died of Alzheimer's disease 29 years after the initial presentation. Three patients are alive with no evidence of disease at 21+, 52+, and 84+ months after treatment. Tumor dissemination occurred after a local recurrence in one patient. We found no evidence of recurrence outside the irradiated field unless there was an initial recurrence at the primary tumor site. We recommend postoperative staging for all patients with pineocytoma and focal radiation therapy if local disease alone is found. Craniospinal radiation therapy appears to be justified only if tumor dissemination is documented on staging tests. PMID- 2910436 TI - Breast carcinoma and plasma 17-beta-estradiol binding. AB - The data relating to plasma steroid binding and transport (usually measured with dehydrotestosterone) are controversial. The plasma E2 binding of 79 breast carcinoma patients, 19 premenopausal and 60 postmenopausal, were compared to 46 controls, 21 premenopausal and 25 postmenopausal. In this study the authors removed the endogenous steroids with charcoal, incubated the plasma with 17-beta E2 in non-saturation conditions, and used ammonium sulfate to precipitate the complex. The authors chose 17-beta-E2 as ligand because the plasma steroid binding system has not been shown to be homogeneous and because this binding function may vary independently for the different steroids. In these patients, the E2 binding was significantly (P less than 0.01) increased (85 +/- 11 pg/ml and 73 +/- 13 pg/ml in premenopausal and postmenopausal) compared to the normal controls (59 +/- 7 pg/ml and 58 +/- 5 pg/ml in premenopausal and postmenopausal women. It is still unclear whether this is a primary increase of the binding capacity or a reaction of the host for sequestering excess circulating E2. However, the small percentage of false-positives and false-negatives suggests that E2 binding could be used as a tumor marker in breast carcinoma. PMID- 2910437 TI - Serum glutathione-S-transferase-pi as a tumor marker for gastrointestinal malignancies. AB - A glutathione-S-transferase-pi (GST-pi) immunoradiometric assay was devised as a potential marker for serodiagnosis of malignant disease. Elevated serum GST-pi levels were observed in patients with various gastrointestinal malignancies including gastric, esophageal, colonic, pancreatic, hepatocellular, and biliary tract cancers. Patients with benign gastrointestinal diseases had normal GST-pi, but some patients with chronic hepatitis and cirrhosis had slightly elevated levels. Over 80% of patients with Stage III or IV gastric cancer and even about 50% of those with Stage I and II had elevated serum GST-pi. After surgery serum GST-pi levels returned to normal. Resected stomach cancers were immunohistochemically positive for GST-pi. During chemotherapy of colonic, gastric, and hepatocellular cancers with a series of different drugs, GST-pi changed in a biphasic manner; increases during initial phases of therapy may reflect acquisition of drug resistance by the tumor. In general, serum GST-pi assays provide a sensitive and reliable marker for gastrointestinal malignancies. PMID- 2910438 TI - Symptoms potentially influencing weight loss in a cancer population. Correlations with primary site, nutritional status, and chemotherapy administration. AB - A nutritional assessment including determination of symptoms potentially influencing weight loss was prospectively performed on 254 consecutive cancer patients with favorable performance scores (Eastern Cooperative Oncology Group [ECOG] level 0 to 2). Primary cancer sites included the following: non-small cell lung (n = 93), colon (n = 50), prostate (n = 23), oropharyngeal (n = 18), breast (n = 15), gastrointestinal (n = 13), and other (n = 42). Thirty-nine percent of patients had received no prior chemotherapy or radiation therapy. Common symptoms in the population were abdominal fullness (61%), taste change (46%), constipation (41%), mouth dryness (40%), nausea (39%), and vomiting (27%). Current caloric intake was surprisingly similar in 170 patients with weight loss (percent usual body weight [PUBW], less than or equal to 95%) compared with 84 without weight loss (PUBW, greater than 95%; 31.4 +/- 1.5 versus 30.5 +/- 2.1 kcal/kg/d, respectively). Symptoms identified by multivariate analysis as occurring significantly more frequently in populations with weight loss included abdominal fullness (P less than 0.001), taste change (P less than 0.002), vomiting (P less than 0.005), and mouth dryness (P less than 0.02). There was no difference in frequency of symptoms between patients with or without prior chemotherapy. These results indicate that gastrointestinal/oral symptoms potentially influencing weight loss are prevalent early in the course of cancer patients with unresectable disease, regardless of current nutritional status, caloric intake, or prior therapy experience. PMID- 2910439 TI - Suprasellar germinomas in childhood. A reappraisal. AB - Germinomas in childhood may arise in both the suprasellar and pineal region, and outcome has been reported to be worse for suprasellar germinomas with a 5-year survival rate of 20% as compared to 60% for pineal germinoma. To determine the factors impacting on outcome, the results of a uniform treatment approach were evaluated and included primary surgical debulking (PSD) and systemic craniospinal axis radiation (CSRT) for suprasellar germinomas. Between 1976 and 1985 ten consecutive patients (seven females, three males) with the pathologically confirmed diagnosis of suprasellar germinoma were treated. Outcome was compared to four male patients with pineal germinoma treated over the same time period and series of patients reported in the literature. At diagnosis the mean age of patients with suprasellar germinoma was 13.9 years (range, 8.9 to 9.4 years). Symptoms were present for a mean of 18 months (range, 2 to 72 months) prior to diagnosis and included diabetes insipidus, anterior pituitary dysfunction, decreased vision, headache, vomiting, and diplopia. Staging studies, including myelography (n = 4) and cerebrospinal fluid cytology (n = 7), disclosed dissemination in only one child. Surgical treatment included biopsy in three cases, partial resection in five, and total resection in two; no permanent postsurgical complications were noted. The mean radiation therapy dose to the tumor site was 4953 cGy (range, 4400 to 5250 cGy) and to the spine 3354 cGy (range, 3000 to 4000 cGy). Patients were followed for a mean period of 5.1 years (range, 1.9 to 10.5 years). One patient with SG who did not receive treatment initially developed a pineal tumor after diagnosis; she was treated with PSD and CSRT and is asymptomatic 5 years later. All the remaining patients are alive and remain disease-free. Surgical resection and CSRT results in excellent disease control for children with suprasellar germinomas, and outcome is similar to those patients with pineal germinoma. PMID- 2910440 TI - The problem of neck relapse in early stage supraglottic larynx cancer. AB - We reviewed the records of 104 patients with Stage T1NO or Stage T2NO epidermoid carcinoma of the supraglottic larynx treated between 1965 and 1979. In 79 patients, surgery was the only type of initial treatment. These 79 patients are the subjects of this report. Forty-eight (61%) of these patients were treated by total laryngectomy, whereas 31 (39%) had a partial laryngectomy. An elective unilateral radical neck dissection was performed on 31 patients considered at high risk, but metastatic disease was found in the dissected side of the neck histologically in only 32% (ten of 31) of these patients. The minimum follow-up period was 5 years and the maximum was 20 years. Twenty-nine percent of the patients (23 of 79) experienced a neck relapse. The neck relapse rate was the same whether the patients did or did not have an elective radical neck dissection. Among the patients who experienced a neck relapse, 65% (15 of 32) have died of the cancer. Among those who did not experience a neck relapse, none (zero of 56) have died of the cancer (P less than 0.01). These results indicate that in surgically treated patients with early stage supraglottic larynx cancer, neck relapse was the major cause of failure associated with death from cancer. Strategies for decreasing the relapse rate are discussed. PMID- 2910441 TI - Combined effect of family history and reproductive factors on breast cancer risk. AB - This study evaluated the combined effect of a family history of breast cancer and each of three reproductive factors on breast cancer risk in the sisters of 404 breast cancer patients. The patients had a family history of breast cancer in a sister and mother or in two sisters. Risks were highest in sisters who had menarche at an early age or who first gave birth at a late age whether the patient had unilateral or bilateral disease, and with low parity only when the patient had bilateral disease. The bilateral group may have included a higher fraction of hereditary forms of breast cancer than the unilateral group. Because similar findings have been reported previously for breast cancer patients in general, the current results suggest that these reproductive factors have an effect on breast cancer risk independent of a family history of the disease. It is important, therefore, that the combined effects of these risk factors be taken into account when counseling women about their breast cancer risks. PMID- 2910442 TI - Coincidence of fundic glandular hyperplasia and carcinoma of the stomach. AB - Eight patients with stomach cancer are described who had also a striking glandular hyperplasia of the fundic mucosa adjacent and remote from the tumor. Five of the eight patients were young women (30 to 37 years of age). The tumors were poorly differentiated carcinomas and six of the eight patients have died of their disease. None of the patients had clinical evidence of endocrine dysfunction including the Zollinger-Ellison syndrome. Immunohistochemistry revealed cells with endocrine differentiation in five of eight tumors, and in two tumors gastrin producing cells were found. Five of seven patients showed increased numbers of antral G-cells. In two patients numerous endocrine (chromogranin-positive) cells were present in the fundic mucosa, specific products of which could not be identified with the antigens tested. No satisfactory explanation exists for this coincidence and its apparent predominance in young female patients. It may be that endocrine substances are responsible for this fundic hyperplasia and that they may also act as promotors of tumor growth. PMID- 2910443 TI - Small bowel carcinoma in Crohn's disease. Distinguishing features and risk factors. AB - An 86-year-old woman who developed small bowel adenocarcinoma 40 years following in-continuity bypass of a 60-cm segment of regional ileitis represents the 22nd reported patient with this complication of bypassed Crohn's disease. Her case demonstrates several of the typical clinical features of such cancers: late recrudescence of disease following a 40-year period of relative quiescence; delayed diagnosis due to misinterpretation of the clinical picture (intestinal obstruction, abdominal mass, intraabdominal abscess, and fistula formation) as due to inflammatory bowel disease; and an exceedingly poor prognosis with rapid widespread local dissemination and death. Histologically, severe dysplasia was demonstrated both in close proximity to and at a distance from the lesion. The increasing number of case reports of adenocarcinoma arising at the site of long standing Crohn's disease, many with dysplasia within areas of diseased bowel, is further evidence that Crohn's disease is a precancerous condition. Physicians must continue to search for methods of earlier diagnosis to improve the prognosis of small bowel carcinoma in Crohn's disease. PMID- 2910444 TI - Peritoneal carcinomatosis in nongynecologic malignancy. A prospective study of prognostic factors. AB - Regional recurrence of malignant tumors in the peritoneal cavity usually signifies a poor prognosis for the host and often results in gastrointestinal complications requiring surgical intervention. One hundred patients with nongynecological malignancies found with peritoneal carcinomatosis were followed prospectively. The most common primary tumors were colorectal (N = 45) and pancreatic (N = 20) carcinoma. When associated with pancreatic carcinoma, 65% of patients had liver metastases and 60% had ascites. The presence of ascites was associated with poor survival, with no patient surviving past 30 days. Ascites was also a sign of poor prognosis in patients with colorectal carcinoma. Among possible prognostic factors in colorectal carcinoma patients, only disease-free interval, presence of lung metastases, and ascites showed statistically significant correlations with survival. Peritoneal carcinomatosis in sarcoma (N = 7) and breast cancer (N = 6) patients had median survival of 12 and 7 months, respectively. Surgical intervention for gastrointestinal complications in peritoneal carcinomatosis can provide significant palliation, with a few exceptions such as in patients with pancreatic or gastric carcinoma, ascites, and poor performance status. PMID- 2910445 TI - Adenocarcinoma of the prostate in cystoprostatectomy specimens removed for bladder cancer. AB - The prostate glands of 84 men undergoing cystoprostatectomy for bladder cancer were examined by whole-mount sections at 4-mm to 5-mm intervals to identify unsuspected prostate adenocarcinoma (PCa). Of 72 white patients with entirely normal digital rectal examinations (DRE), 33 (46%) were found to have PCa, including 12 (17%) who had a Gleason score of 6 or greater and seven (10%) who had penetration through the prostatic capsule. These observations are consistent with previous studies in autopsy populations but allow a more appropriate comparison with morphologic data generated from radical prostatectomy specimens. If these data can be extended to the age-matched general population, treatment at a 1% mortality rate for all white men 60 to 74 years of age with a PCa with a Gleason score of 6 or greater could cause between 6190 and 30,951 deaths, in contrast to 7335 deaths expected from the cancer. These data stress the need for a control group in a study designed to evaluate the benefit of early diagnosis and treatment of PCa. PMID- 2910446 TI - Dysplastic nevi. Markers for increased risk for melanoma. AB - A total of 452 white patients, classified into four dysplastic nevi groups, were followed prospectively by repetitive, complete cutaneous examinations using total body photographs taken on entry into the study. Sixteen patients (3.5%) developed 18 newly diagnosed malignant melanomas (MM) during an average follow-up period of 27 months. Twelve of the 18 MM were in situ, and all of the six primary invasive MM diagnosed prospectively in this follow-up were less than 0.89 mm in Breslow thickness, implying an excellent prognosis. Compared with reference populations, the number of MM detected significantly exceeded the number estimated to occur in the comparable age-matched control groups. These data support the concept of repetitive follow-ups of all groups of patients with dysplastic nevi. PMID- 2910447 TI - Physical and psychosocial functioning and adjustment to breast cancer. Long-term follow-up of a screening population. AB - The effects of age, recency of breast cancer (BC) diagnosis, and severity of the disease on adjustment outcomes were investigated in a sample of 349 women from the 10,056 women screened for BC by the University of Michigan Breast Cancer Detection Demonstration Project between 1974 and 1981. In the 1985 follow-up, data were collected from the 173 surviving BC patients who had invasive BC, and from a matched control group of 176 women who were asymptomatic of BC. Fifty-five percent of the BC patients were 5 years past diagnosis and treatment at the time of data collection. The BC patients group as a whole did not differ from the asymptomatic control group on indicators of mental health, social and psychological well-being, or physical functioning. However, the BC group reported a greater number of diagnosed medical conditions that limited their activities, and taking more medications, than the asymptomatic group. Within the BC group, severity and recency of the cancer had strong independent adverse effects on several of the indicators of mental health and physical functioning. Advanced age had the same main effects in both groups: greater number of medications and diagnosed medical conditions that cause limitations in activities, but, in contrast, better mental health and well-being. Age had interactive effects with the recency and with severity of BC: more recent and severe cases of BC appeared to produce particularly serious difficulties in psychological adjustment for younger patients, and particularly serious medical problems and physical difficulties in adjustment for older patients. PMID- 2910448 TI - A longitudinal analysis of psychological adaptation among survivors of cancer. AB - This longitudinal study examined the psychological adaptation of newly diagnosed cancer patients. Findings showed a decline in patient's mental health status over time. Initial psychological status and other psychosocial factors, and not illness-related factors, were predictive of subsequent adaptation. Two psychologically vulnerable patient groups were identified: those who remained distressed over time and those whose mental health status declined over time. PMID- 2910449 TI - Inhibition of experimental metastasis and extracellular matrix degradation by butanol extracts from B16-F1 murine melanoma. AB - We previously demonstrated that noncytolytic butanol extraction of B16 melanoma cells can increase the number of experimental lung metastases, and that brief incubation of the extracted cells with the extracted moieties reduces metastatic phenotype. This study examined the possibility that the extracted components are endogenous inhibitors of tumor cell surface-associated, degradative enzymes. The activity was found to be tumor associated, since only tumor extracts could reduce the number of experimental lung metastases of a variety of solid tumors. The activity in crude butanol extracts of B16-F1 that modulated the metastatic phenotype of extracted B16-F10 was partially purified by preparative isoelectric focusing and high-performance gel permeation chromatography. Incubation of extracted B16-F10 cells with low (Mr 2,000-10,000) molecular weight materials focusing in the pH 5.6 to 5.8 region of the preparative isoelectric focusing gradient significantly reduced the number of experimental lung foci. Ampholines alone had no effect. Evidence that the extracted moiety might be an endogenous enzyme inhibitor was obtained with the use of the subendothelial matrix degradation assay, wherein B16-F10 cells digest 35S-labeled heparan sulfate proteoglycan. The same materials that reduced the metastatic potential of butanol extracted B16-F10 cells also inhibited extracellular matrix degradation by 30 to 85%, as well as the activity of partially purified heparanase (endo-beta glucuronidase). The metalloproteinase inhibitor 1,10-phenanthroline and the heparanase inhibitor heparin partially (30 to 50%) blocked extracellular matrix degradation. Conversely, inhibitors of serine, thiol, acid, and other proteases had little or no effect on extracellular matrix degradation. These data provide evidence that an endogenous, heat-stable inhibitor of cell surface degradative enzymes such as heparanase may play a role in hematogenous metastasis, and support the hypothesis that butanol extraction activates some of these surface enzymes by removing the endogenous inhibitors. PMID- 2910450 TI - Transport and metabolism of 1-beta-D-arabinofuranosylcytosine in human ovarian adenocarcinoma cells. AB - 1-beta-D-Arabinofuranosylcytosine (araC) is an effective drug in the i.p. therapy of ovarian carcinoma but little is known of its transport and metabolism in this tumor. Influx of araC at 1 microM into cultured human ovarian carcinoma cells (CI 80-13S) was largely inhibited by nanomolar concentrations of the nucleoside transport inhibitor, nitrobenzylthioinosine, while the residual influx (approximately 10%) was inhibited only by micromolar concentrations of nitrobenzylthioinosine. There was a two fold greater density of specific [3H]nitrobenzylthioinosine binding to the nucleoside transporters on the ovarian than on cultured human leukemic cells (RC2a). Calculated turnover rates of the nucleoside transporter for 1 microM araC were 5-fold less in ovarian than in leukemic cells. The major metabolic product of araC was 1-beta-D arabinofuranosylcytosine 5'-triphosphate (araCTP) which accumulated in the ovarian cells to levels half those achieved in the leukemic cells. AraC was the major product of araCTP degradation in ovarian cells consistent with a pathway (araCTP--------araCMP----araC) which is different from that previously found in leukemic cells (araCTP--------araCMP----araUMP----araU). Despite these differences, ovarian carcinoma cells show substantial accumulation of araCTP from extracellular araC. PMID- 2910451 TI - Differential effects on growth, homocysteine, and related compounds of two inhibitors of S-adenosylhomocysteine catabolism, 3-deazaadenosine, and 3 deazaaristeromycin, in C3H/10T1/2 cells. AB - The growth of nontransformed (Cl 8) and malignant (Cl 16) C3H/10T1/2 mouse embryo fibroblasts was inhibited by 3-deazaadenosine (c3Ado) (LD50 = 195 microM for Cl 8 and 30 microM for Cl 16 cells) and 3-deazaaristeromycin (c3Ari) (LD50 about 36 microM for Cl 8 and 9 microM for Cl 16 cells). Both compounds inhibited in a dose dependent manner S-adenosylhomocysteine (AdoHcy) catabolism and homocysteine production, measured as homocysteine egress, and c3Ari was most potent in this respect. c3Ado gave rise to its congener, 3-deazaadenosylhomocysteine (c3AdoHcy). Addition of homocysteine thiolactone (Hcy-tl) to the medium enhanced AdoHcy (and c3AdoHcy) accumulation but did not affect the cell growth at concentrations of inhibitor less than 10 microM. At high concentrations (30-300 microM) both compounds were cytotoxic and decreased cell count when added during midexponential growth. When Hcy-tl was supplemented under these conditions it partly rescued the malignant cells exposed to c3Ari, did not affect the cytotoxicity of this agent towards the nontransformed cells, but greatly potentiated the cytotoxicity of c3Ado against both cell types. Differential metabolic effects were also observed in that high concentrations of c3Ado, but not c3Ari, induced build-up of c3AdoHcy and modulated cellular glutathione level. Growing cells contained the highest amount of glutathione, and in such cells c3Ado induced a significant increase in glutathione whereas the cytotoxic combination of c3Ado plus Hcy-tl decreased the amount of the reduced form. Quiescent confluent cells, which were less sensitive to the toxic effect of c3Ado, contained low glutathione, and under these conditions neither c3Ado alone nor in combination with Hcy-tl affected cellular glutathione. Remarkably, Hcy-tl alone induced an increase in glutathione in nondividing cells. These data suggest that homocysteine or some agents affecting homocysteine metabolism may modulate glutathione metabolism, but differently in dividing and nondividing cells. PMID- 2910452 TI - Induction of erythroid differentiation of K562 human leukemic cells by herbimycin A, an inhibitor of tyrosine kinase activity. AB - Herbimycin A, a benzoquinonoid ansamycin antibiotic, is found to reduce intracellular phosphorylation by tyrosine protein kinase. The human chronic myelogenous leukemia cell line K562 expresses a structurally altered c-abl protein with tyrosine kinase activity. When K562 cells are induced to undergo erythroid differentiation by hemin, reduction in the intracellular level of tyrosine phosphorylation occurs. In order to understand the relationship between induction of differentiation and reduction of tyrosine phosphorylation by the c abl gene product, the effect that herbimycin A, a selective inhibitor of intracellular tyrosine kinase activity, exerts on the differentiation of K562 cells was examined. Reduction of tyrosine phosphorylation in K562 cells by herbimycin A was observed within 1 h. Noncytotoxic concentrations of herbimycin A induced erythroid differentiation of K562 cells but not of murine erythroleukemia 745A cells. The other human myeloid leukemia cell lines (HL-60, THP-1, and U937) tested were not induced to undergo cell differentiation by this antibiotic. Herbimycin A and the other well-known inducers such as hemin, butyric acid, Adriamycin, and 1-beta-D-arabinofuranosylcytosine had additive or more than additive effects on induction of erythroid differentiation of K562 cells. With respect to inhibition of cell growth, the sensitivity of K562 cells to herbimycin A was highest in the human leukemia cell lines we tested. Noncytotoxic concentrations of herbimycin enhanced the antiproliferative effect of Adriamycin or 1-beta-D-arabinofuranosylcytosine on K562 cells. Combination therapy with herbimycin A and its derivatives may be considered for use in the treatment of some types of leukemia where tyrosine kinase activities are implicated as determinants of the oncogenic state. PMID- 2910453 TI - Antitumor activity and murine pharmacokinetics of parenteral acronycine. AB - The lipophilic antitumor alkaloid acronycine (ACRO) was solubilized in the cosolvent system used for etoposide. ACRO in this etoposide diluent (VPD) was found to be cytotoxic (less than or equal to 50% colony formation in soft agar) in fresh human tumors from patients with renal cell cancer, ovarian cancer, uterine cancer, and metastatic tumors of unknown primary. In P-glycoprotein positive, multidrug-resistant (MDR) cell lines, ACRO in VPD was active in MDR Chinese hamster ovary cells but not against MDR L1210 murine leukemia cells, 8226 human myeloma cells, or human CCRF-CEM lymphoblasts. In mice, ACRO in VPD was active in two solid tumor models and an i.p. MOPC-315 plasmacytoma model. ACRO i.p. in 10% VPD (v/v%) produced significant tumor growth delays in (a) nude mice bearing human MCF-7 breast cancer xenografts and (b) C57BL mice bearing colon 38 tumor. In MOPC-315-bearing mice, a single i.p. ACRO dose of 25 mg/kg was as effective as melphalan (15 mg/kg) at prolonging life span. Finally, ACRO pharmacokinetics was evaluated in mice given single 25-mg/kg doses i.p. or p.o. The oral bioavailability of an ACRO solution in VPD was only 50% but both i.p. and p.o. regimens achieved plasma levels greater than 1.0 micrograms/ml. The plasma half-life was just under 2 h. These results show that parenteral ACRO in VPD comprises a cytotoxic antitumor agent with improved bioavailability over p.o. administration. ACRO is active in vitro against several human solid tumors but is cross-resistant in 3 of 4 MDR tumor cell lines. The prior clinical activity of p.o. ACRO in myeloma and the new results in MOPC-315 plasmacytomas in mice suggest that ACRO in VPD could have activity against human multiple myeloma. PMID- 2910454 TI - Augmentation of release of cytotoxin from murine bone marrow and peritoneal macrophages by tumor transplantation. AB - Cytotoxin release by bone marrow-adherent cells and peritoneal macrophages was transiently augmented by i.p. inoculation of syngeneic tumor cells, but not normal cells. These effects were maximal 24-48 h after tumor transplantation. The cytotoxin released from bone marrow-adherent cells obtained 24 h after tumor inoculation had a molecular weight of about 70,000. Peritoneal macrophages obtained 24 h after tumor inoculation released mainly a cytotoxin with a molecular weight of about 55,000, whereas 48-h peritoneal macrophages released both Mr 55,000 and 70,000 cytotoxins. Activities of these three cytotoxins were inhibited by the addition of rabbit anti-murine tumor necrosis factor antibody. No change in expression of antigens on cells producing the cytotoxin was detected in bone marrow-adherent cells obtained 24 h after tumor inoculation, compared to normal bone marrow-adherent cells. However, expression of surface antigens of peritoneal macrophages obtained 24 h after tumor inoculation differed from that of peritoneal macrophages obtained 48 h later. Antigen expression of 48-h peritoneal macrophages producing the cytotoxin was similar to that of 24-h bone marrow-adherent cells producing the cytotoxin. Taken together with the cytotoxin data, it appears that some cells in 48-h peritoneal macrophages may originate from 24-h bone marrow macrophages. These data suggest that the local tumor burden stimulates the central macrophages in bone marrow as well as the local macrophages and that stimulated macrophages in bone marrow may then mobilize to the local site of the tumor transplantation. PMID- 2910455 TI - Progression and selection in heterogeneous tumor composed of androgen-responsive Shionogi carcinoma 115 and its autonomous subline (Chiba subline 2). AB - Shionogi Carcinoma 115 (SC 115) is an androgen-dependent mouse tumor, and Chiba subline 2 (CS 2) is its androgen-independent subline which differs from SC 115 in cell size, amount of androgen receptors, and karyotype. To shed light on the mechanism of clonal selection of androgen-independent tumors, mixed tumors with SC 115 and CS 2 were prepared, and growth of these tumors was examined in vivo and in vitro. When the mixed tumor was transplanted in mice, CS 2 showed a predominant growth over SC 115. In a culture of mixed tumor cells, however, CS 2 showed no selective growth advantage. The suppressive interaction which occurred in vivo was due neither to transferable substances, nor to some immunological factor(s). It may be, at least partially, attributable to necrosis formation in SC 115, which developed with an increase in the size of the tumor. PMID- 2910456 TI - Cell proliferation induced by uracil-calculi and subsequent development of reversible papillomatosis in the rat urinary bladder. AB - The sequence of cellular alterations in urinary bladder epithelium associated with uracil-induced reversible urolithiasis was investigated in male F344 rats. Initial changes were submucosal edema with occasional mucosal erosion or ulceration which appeared on Day 2 of uracil administration. Simple hyperplasia of bladder epithelium was already evident at this time and calculus formation was noted as early as Day 4. Labeling indices in the bladder epithelium assessed by bromodeoxyuridine incorporation were about 32% on Day 4 and then gradually decreased to 6% at Week 8 and 4% at Week 25 of chronic treatment. Histologically, a direct progression from simple hyperplasias, through papillary hyperplasias to papillomatosis, accomplished by Week 5, was evident. Dysplastic lesions were also apparent by Week 25. Topographically, papillomatosis was composed of marked interconnecting mucosal ridges of relatively uniform width. No polyp-like protrusions were present and the vascular pattern revealed by resin perfusion casting demonstrated that these mucosal lesions were supported by a uniform plexus of capillary vessels. After withdrawal of uracil from the diet the labeling index dropped dramatically to 0.002% after 1 week and urolithiasis and papillomatosis had disappeared by Weeks 2 and 3, respectively. The findings suggest that papillomatosis associated with uracil-calculi is a hyperplastic rather than a neoplastic response and that induction of putative neoplastic lesions is directly related to prolonged vigorous cell proliferation. PMID- 2910457 TI - Clonal growth of tumors on tissue-specific biomatrices and correlation with organ site specificity of metastases. AB - We have found that neoplastic transformation alters the ability of cells to grow on substrata of tissue extracts, "biomatrices", enriched in extracellular matrix. Tumor cells were able to survive and grow at lower densities and on more types of biomatrices than normal cells. When plated at high densities (greater than 10(5) cells/60 mm dish), tumor cells attached with equal efficiency and grew at similar rates and to equivalent saturation densities on biomatrices derived from all tissues. However, at low (10(2)-10(4)/60-mm dish) seeding densities, the tumor cells grew only on certain types of biomatrix. For the various hepatoma and mammary carcinoma cell lines tested, the tissue specificity in clonal growth on biomatrices correlated with their organ site specificity for metastasis in vivo in immunosuppressed, athymic nude mice. Analysis of the effects of purified matrix components (adhesion proteins, collagens, glycosaminoglycans) indicated that only the glycosaminoglycans influenced density-dependent survival and growth of tumor cells with effects that differed with respect to the cell's metastatic potential. The results indicate that the ability of tumor cells to colonize specific tissues represents, in part, regulation of low density survival and growth by extracellular matrix and are suggestive that one of the matrix components responsible may be proteoglycans or their glycosaminoglycan chains. PMID- 2910458 TI - Immortal epithelial cells of normal C3H mouse liver in culture: possible precursor populations for spontaneous hepatocellular carcinoma. AB - Long-term culture of primary hepatocytes derived from normal young male C3H/HeNJclMTV+ (C3H) and C57BL/6NJcl (C57) mice, respectively known for very high and low incidences of spontaneous hepatoma, resulted in development of multiple slowly growing epithelial colonies in the C3H case, the number of colonies being increased five-fold when 1.5 mM phenobarbital was added to the culture medium. On the other hand, the primary culture cells from C57 mouse liver gave rise to such epithelial colonies only very rarely, even with phenobarbital. Immunohistochemical investigation revealed alpha-fetoprotein and/or albumin production by the colony cells and ultrastructural analysis also revealed some hepatocytic features in them. Subculturing of individual colonies gave rise to cell lines which could be repeatedly passaged. Two of five lines implanted into athymic nude mice manifested tumorigenicity, the resultant neoplasms being diagnosed as a trabecular hepatocellular carcinoma and an adenocarcinoma. The experimental data suggest that the colony-forming immortal epithelial cells possibly represent early phase precursors of spontaneous mouse hepatocellular carcinomas. This culture system is expected to be useful for future elucidation of the mechanisms underlying spontaneous mouse hepatocarcinogenesis. PMID- 2910459 TI - Normal hepatocytes exhibiting histone H3 with antibody accessible sites that are cryptic in carcinogen-altered hepatocytes. AB - A Mr 14,000 polypeptide (p14), identified as liver fatty acid binding protein, in normal liver cytosol was shown previously to be the principal target of the carcinogen, N-2-fluorenylacetamide (2-acetylaminofluorene), early during hepatic carcinogenesis in rats. Immunohistochemical analyses using rabbit antiserum against pure p14/liver fatty acid binding protein revealed marked increases in the levels of the protein in cytoplasm specifically during mitosis in normal and regenerating hepatocytes, and throughout the cell cycle in hyperplastic and malignant hepatocytes brought about by carcinogen, N-2-fluorenylacetamide (2 acetylaminofluorene) or 3'-methyl-4-dimethylaminoazobenzene. Present also in normal hepatocytes was a nuclear antigen that was not detected in the hyperplastic hepatocytes, benign hepatocytic adenomas, and hepatocellular carcinomas produced by these carcinogens. The nuclear antigen was discerned to be a Mr 17,000 polypeptide (p17) in extracts of normal liver nuclei and nucleosomes. In the present study, the p17 was purified by high-performance liquid chromatography and identified as being the three variants of histone H3, based on common molecular size, amino acid composition, electrophoretic migration in Triton-acetic acid-urea gels, and Western blot and histochemical reactions using affinity-purified antibodies. The histone H3 of all tested organs reacted specifically with the antiserum in Western blots following sodium dodecyl sulfate gel electrophoresis. In contrast, in a survey of 23 normal rat organs, nuclei of virtually only hepatocytes were reactive immunohistochemically. In view of the exceptional immunohistochemical reactivity of nuclei of normal hepatocytes, attributable to accessible histone H3, and the lack of such reaction in carcinogen-altered hepatocytes, the collected evidence indicates that normal hepatocytes contain uniquely available histone H3 sites that become cryptic during the chemical carcinogenesis. PMID- 2910460 TI - In situ hybridization analysis of interstitial C-heterochromatin in marker chromosomes of two human melanomas. AB - Two distinct marker chromosomes, presenting with intercalated C- and distamycin A Dapi-positive regions, were observed in a metastatic and a primary melanoma. To establish the origin of these heterochromatic sequences, we performed in situ hybridization analysis using specific probes for human repetitive DNA. The marker of the primary melanoma, m2, a der 16 chromosome resulting from the translocation of the 1q12-qter segment to band q23 of chromosome 16, showed specific hybridization with Sau3A but not with EcoRI sequences at the interstitial C-band. Thus the origin of this region from the normal chromosome 1 pericentromeric heterochromatin, containing both EcoRI and Sau3A sequences, could be established. On the other hand, the marker of the metastatic melanoma, m1, a der 1 chromosome showing an abnormally banded region inserted between 1q11 and 1q21-qter, failed to give any hybridization signals at the C- and distamycin A-Dapi-positive band when the same EcoRI and Sau3A probes were used. Furthermore, no hybridization was observed using either a probe for SatIII-specific sequences (QP23), mapping to chromosome 9 heterochromatic block, or LS6BB, a ribosomal DNA probe. From these data we speculate that more complex molecular rearrangements may have occurred during the transposition of heterochromatin from its original site to m1. The heterochromatin change found in m1 may be related to advanced stages of malignancy. PMID- 2910461 TI - Cytogenetic analysis of ten human seminomas. AB - A cytogenetic analysis of ten seminomas has been carried out after direct harvesting of the tumor cells. Modal chromosome numbers ranged from 63 to 112. These numbers were in agreement with flow cytometric determination of the DNA content of the tumors. Eight tumors had at least one copy of an i(12p) among other chromosomal abnormalities. Two seminomas lacked the i(12p). PMID- 2910462 TI - Rare clonal karyotypic variants in primary cultures of human breast carcinoma cells. AB - Cytogenetic analyses were performed on 40 previously untreated primary human breast carcinomas, four untreated breast metastases, nine human breast fibroadenomas, and ten normal human mammary tissues, all in primary culture. The results revealed predominantly normal diploid cells with abnormal clones in two of 40 primary carcinomas and one of four metastases. 3p deletion [del(3)(p14 21)], similar to that associated with small cell lung cancer, was found in a primary tumor from a patient with bilateral breast cancer. In addition, a clone with t(1;4) was found in another primary breast carcinoma, while a t(1;5) clone was found in a metastatic tumor. PMID- 2910463 TI - Conversion to the terminally differentiated state during treatment of NG108-15 neural tumor cells with 1-beta-D-arabinofuranosylcytosine in defined medium. AB - Differentiation of cells of the neural tumor hybrid cloned cell line NG108-15 begins stochastically upon transfer to a serum-free defined medium (A. Krystosek, J. Cell. Physiol., 125: 319-329, 1985). Such cultures in N2 medium contain both proliferating and neurite-forming cells (which are not mutally exclusive subpopulations). Addition of 1-beta-D-arabinofuranosylcytosine (ara-C) to NG108 15 cells in N2 medium yielded cultures with a highly differentiated appearance. Investigation of the nature of this effect revealed that ara-C did not increase the probability that cells would enter the differentiation pathway; it did, however, completely abolish proliferation. The early kinetics of neurite formation were similar in control and treated cultures. This was followed by a phase in which ara-C-treated cells underwent continuous rapid maturation including normalization of nucleolar features. Loss of proliferative potential of treated cells was tested in a drug-free serum challenge protocol. Permanently postmitotic cells (i.e., cells which failed to divide even once) were shown to accumulate with time of ara-C pretreatment; this represented 59% of total cells at day 3 and 94% at day 7 of treatment. Thus, the bulk of the population can commit to terminal differentiation. Even among the minority of cells capable of 1 2 rounds of division in the challenge incubation, cessation of proliferation was more likely than continuous colonial growth, suggesting that a profound phenotypic alteration had occurred. The results show that advanced morphological maturation and the step(s) of terminal neuronal differentiation can be achieved in this cell line in response to a cancer chemotherapeutic agent and that this drug is a more complete inducer than compounds which modulate the cyclic AMP system. PMID- 2910464 TI - AIDS-related secular trends in cancer in Los Angeles County men: a comparison by marital status. AB - Data from the population-based cancer registry for Los Angeles County, an area with high risk of AIDS, were used to evaluate secular trends of Kaposi's sarcoma (KS), non-Hodgkin's lymphoma, and other possibly AIDS-related cancers in men aged 18 to 54. Marital status was used as a surrogate for homosexual behavior to compare the proportional incidence rates for the pre-AIDS era, 1972 to 1979, to those for 1980 to 1982 and 1983 to 1985. Both absolute incidence and proportional incidence of KS continue to increase sharply, although in absolute numbers, KS is making a smaller contribution to the total number of AIDS cases as the Los Angeles County epidemic progresses. For never-married men the proportional incidence rate of KS in 1983 to 1985 was nearly 100-fold greater than that of 1972 to 1979 and 7-fold greater than that of 1980 to 1982. High-grade lymphomas show statistically significant secular increases in both never-married and ever married men, but only the rates of Burkitt's lymphomas have increased to a greater extent in never-married men. A small but significant increase of central nervous system lymphomas is seen in both marital status groups. There is no evidence of any AIDS-related increases in Hodgkin's disease, leukemia, testicular cancer, anal cancer, liver cancer, oral cancer, multiple myeloma, or malignant melanoma. As of 1985, cancer, as a manifestation of AIDS, is still apparently limited to KS and high-grade lymphomas (particularly Burkitt's) in Los Angeles County. PMID- 2910465 TI - 4-demethoxydaunorubicin (idarubicin) in combination with 1-beta-D arabinofuranosylcytosine in the treatment of relapsed or refractory acute leukemia. AB - We conducted a Phase I-II trial of 4-demethoxydaunorubicin (idarubicin, IDR) in combination with 1-beta-D-arabinofuranosylcytosine (ara-C) in 51 patients with relapsed or refractory acute nonlymphocytic leukemia, acute lymphocytic leukemia, or chronic myelogenous leukemia in blast crisis. Only 1 of 12 patients treated at the first dose level (idarubicin, 10 mg/m2/day for 3 days and ara-C, 25 mg/m2 i.v. bolus followed by 200 mg/m2 continuous infusion daily for 5 days) achieved aplasia and complete remission. The dose of idarubicin was subsequently increased to 10 mg/m2/day for 4 days with the ara-C dose held constant. Complete remission incidence for this dose schedule was: 7 of 31 patients with acute nonlymphocytic leukemia, 0 of 5 patients with acute lymphocytic leukemia, 0 of 1 patient with chronic myelogenous leukemia in blast crisis, and 1 of 2 patients with biphenotypic leukemia. Nonhematological toxicity included nausea, vomiting, mucositis, and abnormal liver function tests. Detailed pharmacological studies were performed to determine whether ara-C altered IDR metabolism or that of its main metabolite, 13-hydroxyidarubicinol or IDR clearance. A high degree of variability among patients was apparent and no consistent effect could be demonstrated. In summary, 9 of 37 patients (24%) with relapsed or refractory ANLL, including 1 patient with biphenotypic leukemia, achieved remission. We conclude that idarubicin in combination with ara-C is an active combination in patients with relapsed or refractory leukemia. PMID- 2910466 TI - Expression of nucleolar antigen p145 in bone marrow cells of patients with myeloid leukemias. AB - The expression of a cell cycle-related nucleolar protein (p145) antigen was examined in the bone marrow aspirates of 45 individuals, three of whom had no malignant disease; 30 had a diagnosis of acute myeloid leukemia (AML), and 12 suffered from chronic myeloid leukemia (CML). While no evidence of p145 expression was found in the three normal bone marrow samples, it was noted to be the highest in patients with active leukemia, be they AML or blastic crisis of CML. There was a direct correlation between the percentage of blasts and the percentage of p145-positive cells in all patients. Double labeling with tritiated thymidine and p145 in AML patients with active leukemia showed that the majority of S-phase cells contained p145. Myeloblasts in both chronic phase and blastic crisis of CML expressed p145. Nine of 12 AML patients studied during remission had less than 5% p145-positive cells, but three showed 11%, 16%, and 33% positive cells. Since functionally/morphologically, these marrows were normal, the appearance of p145 may indicate a proliferative abnormality preceding maturation arrest and development of relapse. Thus we conclude that p145 is more commonly associated with immature cells and may serve as an early indicator of relapse in AML, but requires further study with larger numbers of patients. PMID- 2910467 TI - Clinical significance of gastrin receptors in human colon cancers. AB - We have measured gastrin receptors (GR) in surgical specimens from 67 patients with primary colon cancers in order to determine the clinical significance of GR in colon cancer. GR analysis was performed on these specimens, and 22 cancers (32.8%) had no detectable GR. Thirty-eight cancers (56.7%) had high-affinity (Kd less than 1.0 nM) levels of GR. Seven cancers (10.4%) had only low-affinity GR (Kd greater than 1.0 nM). Twenty patients (29.9%) had cancers with GR greater than 10 fmol/mg protein. Mean GR content was significantly greater (11.8 +/- 2.9 fmol/mg protein) in Dukes' Stage A and B cancers when compared to Stage C and D cancers (6.2 +/- 1.6 fmol/mg protein). A significantly greater percentage (52.4%) of patients in the early stages (A and B) had tumors with greater than 10 fmol/mg protein compared to patients with more advanced (C and D) cancers (19.6%). GR content did not correlate with histological differentiation, patient age, or preoperative carcinoembryonic antigen levels. No difference in the GR content was noted between left and right colon cancers or in patients of different sex or race. GR content of normal colon mucosa correlated with the GR content of colon cancers from the same surgical specimen, suggesting that these tumors maintain their normal complement of GR. In the early period of follow-up, 12 of 43 (28%) Stage C and D patients with GR less than 10 fmol/mg protein have died, whereas all 8 Stage C and D patients with GR greater than 10 fmol/mg protein are alive. GR content of colon cancers may have prognostic significance and may identify a group of patients with colon cancer that may benefit from hormonal therapy with antigastrin drugs. PMID- 2910468 TI - Tumor-associated mucin-type glycoprotein (CA54/61) defined by two monoclonal antibodies (MA54 and MA61) in ovarian cancers. AB - Two monoclonal antibodies, MA54 and MA61, were established by immunizing with culture medium supernatants of a lung adenocarcinoma cell line, and a double determinant sandwich enzyme immunoassay system was developed by using these two monoclonal antibodies. The antigen recognized by this assay (CA54/61) was found to be often high in the sera of several cancers. The antigen recognized by MA54 (CA54) or MA61 (CA61) proved to be carbohydrate chain on a high molecular weight mucin-type glycoprotein, and CA54 has NeuAc alpha 2-6galactose in the terminal residue. CA54/61 was frequently found in the sera of ovarian cancer patients, the positive rate being 67, 64, 40, and 78% in serous, mucinous, endometrioid, and mesonephroid cancers, respectively, when the cut off value was set at mean + 4 SD. Since the positive rate of CA125, which is now the most widely used for the diagnosis of ovarian cancers, is rather low (approximately less than 50%) in mucinous cystoadenocarcinoma, CA54/61 will be of clinical value. In addition, CA61 was detected immunohistochemically in the fetal red blood cells with nuclei, indicating its oncodevelopmental character in nature. PMID- 2910469 TI - Workshop report from the Division of Cancer Etiology, National Cancer Institute, National Institutes of Health. Protease inhibitors as cancer chemopreventive agents. AB - This workshop was organized to discuss the current state of research on anticarcinogenic protease inhibitors with regard to their potential use as human cancer chemopreventive agents. Previous studies have indicated that protease inhibitors can be powerful anticarcinogenic agents for animals and cells in culture and that human populations known to have high concentrations of protease inhibitors in the diet have low overall cancer mortality rates. In the workshop discussions, emphasis was placed on certain dietary protease inhibitors, such as the soybean-derived Bowman-Birk inhibitor and chymotrypsin inhibitor 1 from potatoes and some of the highly purified protease inhibitors of microbial origin provided by the Japan Society for the Promotion of Science, which have already been shown to contain anticarcinogenic activity in laboratory studies. Potential adverse side effects of dietary protease inhibitors were also considered, specifically, their possible effects on the pancreas and in causing decreased growth rates in young organisms. It was pointed out that the pancreata of a few species, notably rats and chicks, are extraordinarily sensitive to dietary protease inhibitors. Rats fed diets containing high concentrations of soybean derived protease inhibitors (raw soy flour) had enlarged pancreata; increased pancreatic growth is thought to accelerate cancer development in the pancreas. The effect of raw soy flour on the growth of the rat pancreas has not been shown to occur in most other species tested (examples include hamsters, mice, dogs, pigs, and monkeys) and is not expected to occur in humans. There is no evidence that dietary protease inhibitors have adverse effects on the human pancreas. In fact, it has been observed that human populations with high levels of dietary protease inhibitors have decreased rates of pancreatic cancer. Dietary concentrations of protease inhibitors which have been shown to be anticarcinogenic have not produced decreased growth rates in animals or any type of pancreatic pathology. In general, there was a high level of enthusiasm at the workshop for the further development of protease inhibitors as chemopreventive agents. Recommendations for future research include: (a) research and development of sources of protease inhibitors; (b) analysis of human foods for protease inhibitor content; (c) evaluation of cancer incidence data in relation to protease inhibitor content and characteristics in the diet of human populations; (d) animal studies on the efficacy of protease inhibitors in cancer prevention; and (e) studies on the mechanism of action of anticarcinogenic protease inhibitors. PMID- 2910470 TI - Reduced cytotoxicity of the lysosomotropic detergent N-dodecylimidazole after differentiation of HL60 promyelocytes. AB - The sensitivity of the human promyelocytic cell line HL60 to killing by the lysosomotropic detergent N-dodecyl imidazole (C12-Im) has been investigated in the exponential and stationary growth states and before and after differentiation induced by suitable effector molecules. Undifferentiated HL60 cells were more sensitive to killing by C12-Im in the rapid (exponential) phase of growth than in the stationary phase, in keeping with our observations on many other cell lines. Differentiation into granulocytes induced by dimethyl sulfoxide, or into macrophages induced by phorbol ester, resulted in a further dramatic decrease in sensitivity to C12-Im, as compared to undifferentiated HL60 cells in stationary phase. Viable cells remaining after treatment with C12-Im (60 micrograms/ml, 2 h) were: 0% for exponentially growing undifferentiated cells; 16% for stationary undifferentiated cells; 41% for differentiated granulocytes; and 29% for differentiated macrophages. Treatment with the cysteine cathepsin inhibitor L trans-epoxysuccinylleucylamido(4-guanido)butane (E64) conferred resistance to C12 Im, showing that, in these cells, as previously demonstrated for Chinese hamster ovary fibroblasts, cysteine proteases were major cytotoxic agents involved in killing by C12-Im. Cell cathepsin B + L activity levels were dramatically reduced in those cells differentiated into granulocytes (11.2 units/mg of protein) and into macrophages (9.8 units/mg of protein) as compared with undifferentiated HL60 promyelocytes in stationary phase (30.4 units/mg of protein), correlating well with reduced sensitivity to C12-Im in the differentiated cells. PMID- 2910471 TI - Tyrosine kinase activity in breast cancer, benign breast disease, and normal breast tissue. AB - Tyrosine specific protein kinase activity was determined in 70 specimens of the human mammary gland. These included 28 cancers of the breast, 21 benign breast diseases, and 21 normal breast tissues. We measured tyrosine kinase activity in the cytosol fraction and in the membrane fraction of the homogenates. In addition cytosolic aldolase activity was measured. Tyrosine kinase activity was determined using poly(glutamic acid:tyrosine = 4:1) as an artificial substrate. Cancers of the breast exhibited considerable higher tyrosine kinase activities in both cytosol and membrane fractions, compared to benign breast tumors (P less than or equal to 0.001). Benign tumors demonstrated increased activities in cytosol in comparison to normal breast tissues (P less than 0.001). Furthermore, there appears to be a strong association of an enhanced expression of activity of tyrosine kinase in cytosol of primary carcinomas and early systemic relapse. In combination with aldolase activity a nearly complete discrimination is achieved between malignant specimens on one hand and benign and normal tissues on the other. PMID- 2910472 TI - Antitumor activity of murine neutrophils demonstrated by cytometric analysis. AB - The cytostatic and cytolytic activities of activated polymorphonuclear neutrophils (PMNs) against YAC-1 lymphoma target cells were examined using multiparameter flow cytometric analysis. PMNs were resolved from tumor cells by 90 degrees light scatter. The number of surviving tumor cells was determined by adding a known concentration of fluorescent latex particles to the fixed cell suspension immediately prior to analysis and counting the particles simultaneously with the cells. Cell cycle progression of the YAC-1 target was studied by dual parameter analysis of DNA content and bromodeoxyuridine incorporation into tumor cell DNA either prior to or following addition of PMNs. The results indicate that activated PMNs effectively kill tumor cells within the first 24 h of coculture. However, between 24 and 48 h, tumor cells which escape destruction resume growth and eventually reach a growth rate greater than control cells. PMID- 2910473 TI - Involvement of platelet membrane glycoprotein Ib and glycoprotein IIb/IIIa complex in thrombin-dependent and -independent platelet aggregations induced by tumor cells. AB - Involvement of platelet membrane glycoproteins (GP) in interactions between platelets and tumor cells was studied by using two human tumor cell lines and two monoclonal antibodies against platelet membrane GP. HMV-I cells derived from vaginal melanoma induced platelet aggregation in heparinized plasma, which was not followed by coagulation. M7609 cells derived from colon adenocarcinoma also induced platelet aggregation in heparinized plasma, which, on the contrary, was followed by coagulation. Aggregating activities of the HMV-I cells were abolished by pretreatment with neuraminidase or trypsin, but M7609 activity was not labile to these enzymes. Aggregations induced by M7609 were inhibited by hirudin or MD805, while those by HMV-I were not. M7609 cells dose dependently shortened the recalcification time of normal as well as Factor IX-deficient plasmas, while they were not effective in shortening the time of Factor II- or Factor VII-deficient plasmas. The procoagulant activity of HMV-I cells was 1000 times less than M7609 on the basis of cell numbers. When human platelets were preincubated with monoclonal anti-GPIb or anti-GPIIb/IIIa complex antibodies, neither cell line could cause aggregations. These findings suggest that both GPIb and the GPIIb/IIIa complex on the platelet surface are involved in the thrombin-dependent and -independent platelet aggregations induced by tumor cells. PMID- 2910474 TI - Comparison of portal and peripheral blood levels of carcinoembryonic antigen, CA 19-9, and CA 125 tumor-associated antigens in patients with colorectal and pancreatic cancer. AB - Synchronous serum specimens from the systemic and portal circulations of 43 patients with gastrointestinal cancer were assayed for levels of carcinoembryonic antigen, CA 19-9, and CA 125 tumor-associated antigens. The number of patients having a mean ratio of portal to systemic levels greater than 1 and the observed quantity of tumor-associated antigens were significant for carcinoembryonic antigen and CA 125 only in patients with colorectal cancer. No correlations were noted with the surgical stage of disease or with high or low (normal) levels of the three tumor-associated antigens. These findings suggest that peripheral concentrations of these antigens are in equilibrium with shedding from tumors and that hepatic clearance of a single pass does not significantly alter peripheral concentrations. PMID- 2910475 TI - Fecal diglycerides as selective endogenous mitogens for premalignant and malignant human colonic epithelial cells. AB - Diglycerides (DGs) have been found in fecal extracts at concentrations which induce mitogenesis of adenoma and some carcinoma cells but not normal cells in primary culture. DGs containing stearic, oleic, palmitic, and myristic acid side chains were found in fecal extracts from each of eight subjects. Synthetic 1,2 DGs, containing the fatty acids found in endogenous fecal DGs, induced mitogenesis in cultures of premalignant cells from each of 13 adenomas, covering all histological classes, and in cultures from two of four carcinomas. The potent adenoma mitogen, dimyristin, had no mitogenic activity on cultures of normal colonic epithelial cells from seven different subjects. These results suggest DGs may act as endogenous mitogens in the development of human colon cancer. The extent of adenoma mitogenesis was correlated with the chain length of the saturated R-groups: 16 greater than 14 greater than 12 greater than 10 greater than 8 much greater than 18. DGs with oleic acid residues, C18:1, were among the most active, while substitution of even one fatty acid residue with a stearic acid residue, C18:0, reduced or eliminated mitogenic activity. Dimyristin also induced enhanced levels of urokinase secretion from carcinoma cells, in parallel to the phorbol ester tumor promoter, 12-O-tetradecanoylphorbol-13-acetate. These results imply that DGs found in the colon induce a selective growth of benign colonic tumors and some carcinomas, and may enhance the invasive capacity of carcinomas, while leaving normal cells unaffected. PMID- 2910477 TI - Chlorambucil pharmacokinetics and DNA binding in chronic lymphocytic leukemia lymphocytes. AB - Chlorambucil (CLB) uptake by chronic lymphocytic leukemia lymphocytes was studied using a radiometric and a newly developed high-performance liquid chromatography assay. CLB labeled with 14C in either the chloroethyl group or phenyl ring was used with identical results. Drug accumulation by the cells was found to peak at 30 s, was independent of temperature, and was proportional to medium CLB concentration over a wide range. Efflux from cells loaded with CLB and resuspended in drug-free medium was nearly complete at 30 s. The metabolic inhibitors 2-deoxyglucose and NaN3, the nitrogen mustard transport inhibitor hemicholinium-3, and another alkylating agent, melphalan, had no effect on drug uptake. We conclude that CLB enters and exits chronic lymphocytic leukemia lymphocytes by simple diffusion. Cells from 17 patients with all stages of chronic lymphocytic leukemia were studied including three with CLB-resistant disease, and no heterogeneity was found in the peak cell-associated CLB content or in metabolite pattern on high-performance liquid chromatography. These findings make it unlikely that transport or cellular drug metabolism are factors in drug resistance. Drug-DNA binding was found to be temperature-sensitive and increased with time of incubation. Gel filtration of DNA before and after enzymatic digestion indicated the presence of drug-DNA adducts. High-performance liquid chromatography analysis of digested DNA and DNA treated by neutral thermal hydrolysis suggested the presence of multiple adducts. Most of the radioactivity was found as purine adducts. Studies with CLB labeled at two different sites revealed the presence of the phenyl group and ethyl chains in the adducts. A survey of patients showed increased drug-DNA binding in cells from patients with clinical CLB resistance. PMID- 2910476 TI - Inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced DNA adduct formation and tumorigenicity in the lung of F344 rats by dietary phenethyl isothiocyanate. AB - F344 rats fed diets containing phenethyl isothiocyanate (PEITC, 3 mumol/g diet), a cruciferous vegetable component, before and during treatment with the tobacco specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), developed about 50% fewer lung tumors than NNK-treated rats fed control diets. NNK-induced liver and nasal cavity tumors in rats were, however, not affected by this dietary treatment. The effects of PEITC diets on the formation of DNA adducts by NNK were also investigated in these target tissues. DNA methylation and pyridyloxobutylation by NNK were both decreased by 50% in lung of rats fed PEITC diets compared to that of rats fed control diets, but the levels of DNA methylation were not affected in liver and nasal mucosa. These results correlated with those from the carcinogenicity bioassay, suggesting that DNA alkylations could be used as indicators for screening inhibitors of NNK tumorigenesis. A slight increase in the number of tumors of the exocrine pancreas was observed in PEITC-fed rats with or without NNK treatments. However, these incidences were not statistically significant when compared to the control groups. The potential toxicity of PEITC at concentrations ranging from 0.75 mumol to 6 mumol/g diet was evaluated in a 13-week study. The only toxicity caused by this treatment was minimal fatty metamorphosis in the liver. Considering the widespread human exposure to NNK through tobacco use, it is of practical importance to demonstrate inhibition of lung tumors induced by this carcinogen. These results provide a basis for studies designed to discover agents of better efficacy for the prevention of NNK-induced tumorigenesis. PMID- 2910478 TI - Correlation between growth inhibition and intranuclear doxorubicin and 4'-deoxy 4'-iododoxorubicin quantitated in living K562 cells by microspectrofluorometry. AB - Intranuclear drug concentration in cells treated with doxorubicin (DXR) or with 4'-deoxy-4'-iododoxorubicin (IDX) was measured by means of a quantitative microspectrofluorometric technique recently developed by us. Resolution of free and bound drug contributions in fluorescence emission spectra, as collected from a microvolume of single living cell nuclei, provided concentration data with about 10% indetermination. Uptake of DXR and IDX into the nucleus of K562 cells and DXR-resistant K562/DXR cells could then be studied with a sensitive, nondestructive technique. Growth inhibitory concentrations of K562 and K562/DXR cells, when measured with respect to drug content in the medium, differed by a factor of 25 in the case of DXR and by a factor of three in the case of IDX. By contrast, intranuclear drug concentrations measured at corresponding growth inhibitory concentrations are found to be nearly constant, i.e., independent of cellular-resistant phenotype and of anthracycline structure. This result supports an identical mechanism of action for the two drugs, most probably targeted to the nucleus, and ascribes to intracellular transport the different potency of the two drugs in the two cell lines. PMID- 2910479 TI - Tumor cell dissemination patterns and metastasis of murine mammary carcinoma. AB - Quantitative studies on the distribution kinetics of isotope-labeled cells from spontaneous murine mammary tumors injected intravenously or arterially showed that cells were rapidly distributed to all organs examined and indicated that the distribution patterns of metastases from such tumors are not primarily determined by the dose of cells delivered to each organ. The preferential colonization of certain organs is therefore considered to depend as much on differential survival and growth of the disseminated tumor cells in unfamiliar metabolic microenvironments, as on vascular sieving effects in organ capillary networks. Further experiments involved transplantation of pieces of nonpulmonary tissue containing trapped mammary tumor cells into syngeneic mice, followed by observation of the animals for several months. From these studies it is concluded that the absence of tumor colonies in extrapulmonary sites after i.v. inoculation is due to their inability to thrive in the organs concerned and not to early death of the original host from heavy pulmonary tumor growth. These results provide further evidence strengthening the conclusion emerging from several independent lines of investigation (Potter et al., Invasion Metastasis, 3: 221 233, 1983; Tarin et al., Cancer Res., 41: 3604-3609, 1981; Tarin et al., Cancer Res., 44: 3584-3592, 1984; Horak et al., J. Natl. Cancer Inst., 76: 913-922, 1986; Nicolson et al., Int. J. Cancer, 38: 289-294, 1986; Naito et al., Invasion Metastasis, 7: 16-29, 1987) that the growth of disseminated tumor cells is inhibited or even abrogated by many of the organs in which the cells sequester after vascular dissemination. PMID- 2910480 TI - Detection of somatic mutations at the glycophorin A locus in erythrocytes of atomic bomb survivors using a single beam flow sorter. AB - A modified method was developed for measuring the frequency of variant erythrocytes at the glycophorin A locus using a single beam cell sorter (SBS). Fluorescein- or phycoerythrin-labeled monoclonal antibodies specific for the M or N glycophorin A alleles were used for the SBS assay. To prevent contamination of nucleated cells in the sorting windows, the nucleated cells in the fixed erythrocyte sample were stained with propidium iodide before flow sorting. Blood samples were obtained from atomic bomb survivors who were heterozygous for the MN blood type, and the frequencies of the hemizygous and homozygous variant of the M or N glycophorin A allele were measured by the SBS. For the three types of variants, hemizygotes for M and N allele (No and Mo) and homozygotes for M allele (MM), the variant frequency measured by the SBS correlated well with that previously determined by a dual beam cell sorter. Variant frequencies of the No, Mo, and MM cell types in atomic bomb survivors determined by SBS measurements were found to increase with radiation dose (DS86, kerma) as well as with the frequency of chromosome aberrations in lymphocytes. PMID- 2910481 TI - Effect of novobiocin on the antitumor activity and tumor cell and bone marrow survivals of three alkylating agents. AB - Our previous in vitro studies demonstrated marked synergy with alkylating agents when novobiocin was present during and after alkylating agent exposure. To determine whether this effect is observed in vivo, novobiocin was administered daily for 3 days prior to alkylating agent treatment, during alkylating agent treatment, and for 2 days after completion of alkylating agent treatment. When combined with cis-diamminedichloroplatinum(II), 1,3-bis(2-chloroethyl)-1 nitrosourea, or cyclophosphamide, there was significant enhancement of the growth delay of the FSaIIC fibrosarcoma implanted s.c. in C3H mice when compared with alkylating agents alone. In a second assay using ex vivo studies of tumor cells exposed in vivo, single doses of 100 mg/kg of novobiocin followed by cis diamminedichloroplatinum(II) resulted in a 3- to 4-fold increase in tumor cell killing by cis-diamminedichloroplatinum(II). At a dose of 100 mg/kg of 1,3-bis(2 chloroethyl)-1-nitrosourea there was about a 7-fold increase in tumor cell kill upon addition of novobiocin. Cyclophosphamide showed a dose response effect with novobiocin, reaching 13-fold at a dose of 300 mg/kg of cyclophosphamide. In all cases bone marrow elements were affected less than were neoplastic cells, suggesting that the combination of novobiocin and alkylating agents may be a clinically useful strategy. PMID- 2910482 TI - Mouse retroviral sequences acquired by cell lines after passaging through nude mice detected by hybridization of the fms probe pSM3. AB - The expression of a large RNA transcript, 8.5 to 9.5 kilobases, possibly related to the fms oncogene in mouse, rat, and human tumor cells, has been described in the literature. However, the pSM3 fms probe used to detect this gene transcript contains a significant amount of the pol gene of the Susan McDonough strain of feline sarcoma virus from which it was derived. Using a fms probe which does not contain any viral pol sequences, no such "fms-related" transcripts were detected in cell lines previously reported to express the large transcripts. These cell lines did express a large 9.5-kilobase transcript which hybridized to a probe for murine leukemia virus. Partial sequence analysis of the 9.5-kilobase transcript detected with the pSM3 probe in transformed rat cells indicated sequence homology with AKV murine leukemia virus. Thus, the presence of large RNA transcripts, interpreted by us and others as being related to the oncogene fms, appears to be due to the expression of mouse retroviral sequences which hybridize to the viral pol region contained in the pSM3 fms probe. In the case of rat and human cells, such sequences appear to be acquired after the cells have been passaged in nude mice. These results should serve as a reminder of the important biohazard and data interpretation implications for investigations in which cells transfected with retroviral vector constructs are injected into nude mice, because rescue of the recombinant sequences in these cells could occur following infection by endogenous murine retroviral particles. PMID- 2910483 TI - 1,2-Dimethylhydrazine-induced alterations in N1-acetylspermidine levels and spermidine N1-acetyltransferase activity in rat colonic mucosa. AB - To determine whether alterations in the "reverse" or "conversion" pathway for putrescine formation were involved in the induction of colonic tumors by 1,2 dimethylhydrazine, male albino rats of the Sherman strain were given injections s.c. of this agent (20 mg/kg body weight/week) or diluent for 5, 10, 15, and/or 26 weeks. Animals were sacrificed at each of these time periods and polyamine levels, including N1- and N8-acetylspermidine, as well as the activities of ornithine decarboxylase, spermidine N1-acetyltransferase and polyamine oxidase were measured and compared in rat proximal and distal colonic mucosa of each group. The results of these studies demonstrated that: (a) N1- and N8 acetylspermidine levels were similar in the control and treated proximal colonic segments at all time periods examined; (b) N1- and N8-acetylspermidine levels were also similar in the control and treated distal colonic segments at 5 and 10 weeks; (c) at 15 weeks the level of N1-acetylspermidine, but not N8 acetylspermidine, however, was increased in the treated distal colonic segment secondary to increases in the activity of spermidine N1-acetyltransferase; and (d) at 26 weeks, the level of N1-acetylspermidine remained higher in treated distal "uninvolved" colonic tissue and were markedly elevated in colonic tumors in both segments. Based on these findings, it would appear that the reverse pathway for putrescine formation may be involved in the 1,2-dimethylhydrazine induced malignant transformation process of the rat colon. PMID- 2910484 TI - Clonal chromosome abnormalities in tumor cells from patients with sporadic renal cell carcinomas. AB - The karyotype of 75 sporadic, nonpapillary renal cell carcinomas was analyzed using chromosome banding techniques. Sixty-five tumors had near-diploid stemlines, and ten had near-triploid or near-tetraploid stemlines. Aberration of chromosome 3 was detected in 71 cases. The nonrandom changes on chromosome 3 were monosomy 3, terminal deletions, or unbalanced translocations; the 3p13-pter segment was identified as the minimal common deletion. The rearrangement of chromosome 3p was the only karyotype change in 13 tumors. Abnormalities of chromosome 5 resulting in trisomy for the 5q22-qter region were found in 36 cases, while the loss of 14q22-qter segment was observed in 34 tumors. Trisomy for chromosome 7 was detected in 17 cases, and monosomy 8 and 9 occurred 14 times each. Our data show that more than one specific chromosomal site may be involved in the development of human renal cell carcinomas. PMID- 2910485 TI - Progression of transplanted SJL/J lymphomas attributed to a single aggressive H 2Ds-negative lymphoma. AB - Spontaneously arising, H-2Ds-positive SJL/J lymphomas have been reported to become irreversibly more aggressive and H-2Ds-negative upon successive transplantation in syngeneic mice. In an effort to determine whether this process was one of tumor progression, we sought to: (a) establish whether a clonal relationship exists between readily transplantable aggressive SJL/J lymphomas and their respective indolent predecessors; and (b) identify genetic events critical to the process of acquisition of increased malignancy. Examination of putatively distinct, aggressive, H-2Ds-negative lymphomas, including the long term transplantable line RCS5, revealed them to have the same heavy and light immunoglobulin chain gene rearrangement patterns, a characteristic karyotype marked by nine chromosomal abnormalities, and approximately ten newly acquired ecotropic murine leukemia proviruses at similar genomic sites. Independent, spontaneously arising H-2Ds-positive lymphomas, in early transplant, were found to be genetically distinct from the respective more malignant H-2Ds-negative tumors to which they gave rise during successive transplantation. The data are interpreted as indicating that the aggressive H-2Ds-negative tumors in this study originated from a common source, most likely the RCS5 tumor, rather than through progression of separate spontaneously arising SJL/J lymphomas. It cannot be concluded which of the multiple genetic abnormalities of the H-2Ds-negative tumors were critical to their highly malignant phenotype. However, chromosomal abnormalities and newly acquired murine leukemia proviruses are discussed as to the roles they might play in SJL/J lymphomas. PMID- 2910486 TI - Chromosomal changes in mature residual teratomas following polychemotherapy. AB - A cytogenetic analysis of 13 mature residual teratomas following chemotherapy revealed modal chromosome numbers ranging from 52 to 85, in agreement with the flow cytometric determination of the DNA content of the tumors. At least one copy of an i(12p) was present in 12 tumors. One tumor, however, lacked that marker. The comparison between the chromosomal abnormalities found in mature residual teratomas following chemotherapy and those from primary testicular nonseminomas suggests that residual teratomas result from selection of clones from the primary tumor with a less abnormal karyotype. PMID- 2910487 TI - Cyclosporin A and verapamil enhancement of daunorubicin-produced nucleolar protein B23 translocation in daunorubicin-resistant and -sensitive human and murine tumor cells. AB - It has recently been shown that anthracycline antibiotic-resistant tumor cells are less responsive to daunorubicin-stimulated B23 nucleolar phosphoprotein translocation than drug-sensitive cells. Since cyclosporin A and verapamil reverse primary acquired and secondary cross-resistance to daunorubicin, we investigated the effect of these agents on nucleolar B23 translocation in sensitive and resistant tumors. We compared modified to baseline B23 phosphoprotein distribution between predominantly nucleolar, mixed nucleolar nuclear, or nuclear immunofluorescence using a monoclonal anti-B23 antibody in parental drug-sensitive and multidrug-resistant acute lymphatic leukemia and in daunorubicin-sensitive and -resistant murine hepatoma. Our experiments show that cyclosporin A and verapamil alone have no effect on B23 phosphoprotein translocation, but that the addition of either agent to sensitive parental or resistant tumor sublines markedly enhances daunorubicin-stimulated translocation. This effect correlates with the correction of impaired daunorubicin inhibition of RNA synthesis by cyclosporin A and verapamil in the resistant sublines. Our observations suggest that nucleolar B23 phosphoprotein is an important site in the modulation of anthracycline antibiotic antitumor activity. PMID- 2910488 TI - Relationship between extracellular matrix interactions and degree of differentiation in human colon carcinoma cell lines. AB - Human colon carcinoma cell lines that vary in their degree of differentiation were examined for their ability to interact with extracellular matrix components. For this purpose, established cell lines were classified on the basis of several criteria that relate to degree of differentiation. These criteria include histology of the original tumor, histology of xenografts, in vitro morphology, and carcinoembryonic antigen expression. On this basis, the cell lines used were either moderately well or poorly differentiated. The poorly differentiated cell lines adhered to surfaces coated with laminin or reconstituted basement membrane extract (Matrigel) to a significantly greater extent than the moderately well differentiated lines with the exception of one moderately well differentiated line that was derived from a highly aggressive signet ring cell carcinoma. In addition, the poorly differentiated cell lines exhibited considerable spreading on laminin and Matrigel after adherence that was not evident for the moderately well differentiated lines. The adherence of these cell lines on fibronectin coated surfaces did not correlate as well with differentiation although, in general, poorly differentiated cell lines adhered better than moderately well differentiated lines. None of the cells that adhered to fibronectin exhibited the extensive spreading seen on laminin. The specificity of tumor cell interactions with extracellular matrix glycoproteins was examined using synthetic peptides which correspond to sequences within these proteins that are recognized by cell surface receptors. The pentapeptide YIGSR-NH2 significantly inhibited the adherence and spreading of the tumor cell lines on laminin, but not on fibronectin. The peptide RGDS, however, did not inhibit tumor cell interactions with laminin although it did inhibit their interactions with fibronectin. Thus, the interactions of colon carcinoma cells with laminin and fibronectin are probably mediated by separate receptors. Taken together, the data demonstrate that cells derived from colon carcinomas exhibit considerable variation in their ability to interact with extracellular matrix components, and that this variability is related to the degree of differentiation of original tumor. PMID- 2910489 TI - Monoclonal antibodies to a rat colon carcinoma: model for monoclonal antibody therapy of solid tumors. AB - Tumor progression, lung metastasis, and death occur in tumor-bearing BD IX syngeneic rats in a fashion similar to the course of patients with metastatic colon cancer. In an effort to establish a relevant model for monoclonal antibody (MoAb) therapy of tumors, we generated murine MoAb against DHD/TR, a dimethylhydrazine-induced rat colon carcinoma which has been adapted to cell culture. Murine MoAb 17B10 E4 (E4) reacts with the TR tumor and shows weak immunoperoxidase reactivity with normal rat tissues. Murine MoAb 5F7 D3 (D3) reacts with the tumor and a variety of normal rat epithelia. Both are IgG2a and mediate cytotoxicity by rat peripheral blood mononuclear cells. 18D5 F6 (F6) also reacts with the tumor and normal tissues but is an IgG2b and does not mediate cytotoxicity in the presence of rat effector cells. Iodinated E4 and D3 antibodies retained their immunoreactivity. E4 revealed 9.8 x 10(5) antigenic sites per TR cell, with an affinity constant of 9.35 x 10(7) M-1, while D3 demonstrated 2.5 x 10(6) antigenic sites and an affinity constant of 4.2 x 10(7) M-1. Immunoblotting showed that the antigens recognized by D3 and E4 are glycoproteins with molecular weights of 27,000 and 66,000, respectively. F6 failed to react with its antigen present in the blot. This rat colon carcinoma and the monoclonal antibodies described here may provide experimental data useful for implementing monoclonal antibodies in cancer therapy. PMID- 2910490 TI - Androgen dependency of a tumor produced by a cell line derived from androgen responsive Shionogi carcinoma 115. AB - An androgen-dependent tumor (SCC8 tumor) was obtained by inoculating an androgen responsive cell line derived from the androgen-responsive Shionogi carcinoma 115 (SC115) into mice and then treating the mice with testosterone propionate (TP) at a pharmacological dose (400 micrograms/day). The SCC8 tumor differed in histological appearance from the SC115 tumor and its growth was less stimulated by androgen than that of the SC115 tumor. However, its growth was completely androgen dependent; SCC8 tumors did not develop in castrated mice and regressed when TP treatment was discontinued. The decreased sensitivity of the SCC8 tumor seemed to be attributable in part to its rapid metabolism of testosterone to metabolites with lower androgenic actions. The effects of TP at doses of 0, 100, 200, and 400 micrograms/day on cell division and cell death in SCC8 tumors of medium size were examined by measurements of the mitotic index and the retention of 5-[125I]iodo-2'-deoxyuridine incorporated into the whole tumor. TP increased the mitotic index dose dependently and at all doses reduced the decrease in the retention of 5-[125I]iodo-2'-deoxyuridine. These results suggest that steroids may not only stimulate cell division but also reduce cell death in steroid dependent tumors. PMID- 2910491 TI - Cancer in Costa Rica. AB - Data from the national tumor registry of Costa Rica for the years 1979-1983 have been used to calculate incidence rates for the major cancer sites by age, sex, urban-rural residence, and geographic region. Recent trends in mortality rates are also presented. Results are compared with data from elsewhere in Latin America, U.S.A., Europe, and Japan. Stomach cancer is the most frequent neoplasm in Costa Rica; although rates are declining, they are second only to those observed in Japan. There are marked variations in risk by region, suggesting important environmental influences in etiology. The cervix is the major female site; rates are declining in young women, probably due to the introduction of screening programs, although these do not seem to account for the geographic variations in invasive cancer incidence. Breast and prostate cancer show moderate rates, while those for colon and rectum cancer are low; increases in mortality rates for these sites are small, and involve mainly the older age groups. In contrast, rates of lung cancer are increasing dramatically in both sexes. In the childhood age group, very high incidence rates are observed for two neoplasms: Hodgkin's disease and acute lymphocytic leukemia. PMID- 2910492 TI - Auditory function in pediatric osteosarcoma patients treated with multiple doses of cis-diamminedichloroplatinum(II). AB - Serial auditory evaluations were performed in 54 pediatric patients (5 to 18 yr) treated with cis-diamminedichloroplatinum(II) for osteosarcoma. Each course of cis-diamminedichloroplatinum(II) comprised 150 mg/m2 and was administered initially at two weekly intervals for seven courses (3 mo) and subsequently at three monthly intervals for 15 to 21 mo. Overall, 604 courses were administered, and observations were conducted from diagnosis to 6 yr. Bilateral hearing loss was detected in all patients. The loss varied from mild (20 to 40 dB) to profound (greater than 90 dB). Initial losses occurred in the higher frequencies and were also greater at these frequencies. Significant loss was first observed after 300 mg/m2 for frequencies over 4000 Hz and gradually shifted to incorporate the lower frequencies. Hearing loss was permanent. PMID- 2910493 TI - Expression of Lewisa, Lewisb, Lewisx, Lewisy, siayl-Lewisa, and sialyl-Lewisx blood group antigens in human gastric carcinoma and in normal gastric tissue. AB - A panel of 6 mouse monoclonal antibodies detecting blood group antigens of the Lewis systems and their sialylated derivatives have been used to define the immunoanatomic distribution of these antigenic structures within the normal human gastric mucosa and in gastric cancer tissues. The reagents employed detect the following blood group specificities: Lewisa, Lewisb, Lewisx, Lewisy, sialylated Lewisa, and sialylated Lewisx. We have analyzed the presence of these antigens in histologically normal gastric mucosa and in gastric carcinoma from 61 patients by the immunoperoxidase method. In addition, we simultaneously examined the blood group and secretor status in 31 of the 61 individuals studied. Immunohistochemical analysis revealed that these antigenic systems are differentially expressed in cell types and cell layers of the normal gastric epithelium. Major differences were observed in surface epithelia and in deep glands including Brenner's gland of the gastroduodenal junction, mainly in the pronounced expression of Lewisa and Lewisb antigens in the former and the expression of Lewisx and Lewisy in the latter. In secretor individuals, Lewisb was the dominant antigen in the surface epithelium, and in nonsecretors, Lewisa was observed in the surface epithelium, Lewisx and Lewisy were both detected in the deep glands and in Brenner's glands regardless of the secretor status. The expression of sialylated derivatives in normal gastric tissues was considerably reduced but was consistent with the expression of their precursors in normal gastric epithelium. In gastric cancers, more pronounced expression of Lewisa and sialylated Lewisa was observed in secretor individuals and acted as a tumor associated antigen. Comparison of the plasma level of sialylated Lewisa and its tissue expression demonstrated that the shedding of the antigen into interstitial stroma correlated with the detection of the antigen in serum. These studies confirmed the importance of blood group antigens as normal differentiation antigens. Examination of secretor status clarified the mechanism of Lewisa and Lewisb antigen expression in gastric surface epithelium. Alterations in the expression of these antigens and an increase of sialylated derivatives in gastric cancers demonstrated that these blood group antigens are useful tools for the analysis of histogenesis and organogenesis in the stomach and its neoplastic and nonneoplastic diseases. PMID- 2910494 TI - Comparative pharmacokinetics and alkylating activity of fractionated intravenous and oral ifosfamide in patients with bronchogenic carcinoma. AB - 20 patients with advanced non-small cell lung cancer were treated with ifosfamide and mesna 1.5 g/m2 daily for 5 days; 10 received the drug by mouth and 10 i.v. Both schedules resulted in a reduction in the elimination half-life with an increased total and nonrenal clearance of ifosfamide over the 5-day period. Oral administration resulted in an unacceptably high incidence of encephalopathy(5/10) which was not seen in the i.v. group. In two patients this encephalopathy manifested itself as coma which lasted for 24 to 48 h but was fully reversible and in the other three cases as somnolence occurring for more than 50% of the patients' waking hours. Nadir blood counts and response rates were similar in both arms. The encephalopathy suggests that there are metabolic differences between the i.v. and oral routes and that a metabolite rather than the parent drug is responsible for this syndrome. In addition it was shown that the total and nonrenal clearance of the drug was significantly less when the drug was administered orally. None of the pharmacokinetic parameters either singly or in combination predicted for ifosfamide toxicity. No correlation between the creatinine clearance and ifosfamide renal clearance was demonstrated suggesting tubular reabsorption of the drug. In conclusion, ifosfamide cannot be given orally at the conventionally employed i.v. doses. PMID- 2910495 TI - The MerR heavy metal receptor mediates positive activation in a topologically novel transcription complex. AB - Several physical and chemical signals from the extracellular environment are known to be transduced into changes in gene expression through multiple step pathways; however, mechanisms for triggering cellular responses to heavy metal stress have yet to be elucidated. We demonstrate here one such mechanism that employs a single heavy metal receptor protein, MerR, to directly activate transcription of the bacterial mercuric ion resistance operon. The mercuric ion MerR complex and E. coli RNA polymerase holoenzyme synergistically bind to the metal responsive promoter in an unprecedented spatial relationship to form transcriptionally competent complexes. The activator binds adjacent to and overlaps with the polymerase molecule between the consensus -35 and -10 promoter regions. Our results support a model for transcriptional activation that includes both effector-induced protein-protein interactions and activator-induced alteration in DNA structure. PMID- 2910496 TI - Mouse RNAase MRP RNA is encoded by a nuclear gene and contains a decamer sequence complementary to a conserved region of mitochondrial RNA substrate. AB - Using complementary oligonucleotide probes, we have isolated the nuclear gene for the RNA moiety of RNAase MRP; it is present as a single copy and encodes an uncapped primary transcript of 275 nucleotides. Direct sequence analysis revealed that the 136 nucleotide RNA that copurifies with RNAase MRP represents the 3' half of the 275 nucleotide primary transcript. The 5'-flanking region of the gene has putative transcriptional control elements homologous to the promoters of RNA polymerase II-transcribed U-series snRNA genes; however, the coding region possesses a box A sequence and terminates at four T residues, both features characteristic of polymerase III-transcribed genes. A decamer sequence, 5'-CGA CCCCUCC-3', complementary to a conserved sequence adjacent to the enzymatic cleavage site on the mitochondrial RNA substrate, is present in the RNAase MRP RNA. Isolation of a nuclear gene for the RNA component of a mitochondrial enzyme implies that nucleic acids can be transported across mitochondrial membranes. PMID- 2910497 TI - SV40 large T antigen binds preferentially to an underphosphorylated member of the retinoblastoma susceptibility gene product family. AB - Extracts of monkey cells (CV-1P) synthesizing SV40 large T antigen (T) were immunoprecipitated with monoclonal antibodies to T or p110-114Rb, the product of the retinoblastoma susceptibility gene (Rb). While a family of p110-114Rb proteins can be detected in anti-Rb immunoprecipitates, only one member of this family, p110Rb, was found in anti-T precipitates of these extracts. Identical results were obtained with extracts of CV-1P cells which had been previously mixed in vitro with highly purified T. The p110-114Rb family is composed of two sets--p110Rb, an un- or under-phosphorylated species, and pp112-114Rb, a group of overtly phosphorylated proteins. Thus, T bound preferentially to the un- or underphosphorylated member of the family. In addition, T failed to alter the relative abundances of these species. These results suggest a model in which the growth suppression function of Rb is down modulated either by phosphorylation or T antigen binding. PMID- 2910498 TI - The helical repeat of nucleosome-wrapped DNA. PMID- 2910499 TI - The cell surface of mouse dendritic cells: FACS analyses of dendritic cells from different tissues including thymus. AB - The surface of dendritic cells from mouse spleen, thymus, and epidermis has been compared with a panel of monoclonal antibodies and the FACS. A method was first developed to isolate populations of large, adherent, thymic dendritic cells that were greater than 90% pure. These were released by collagenase digestion and separated from adherent macrophages after overnight culture. Enrichment was based on the facts that most macrophages remained plastic adherent and rosetted strongly with antibody-coated erythrocytes. As in spleen, thymic dendritic cells were stellate in shape, had abundant class I and II MHC products, lacked many standard macrophage and lymphocyte markers, and actively stimulated the mixed leukocyte reaction. Most spleen and thymic dendritic cells could be lysed by the 7D4 mAb, to the low-affinity IL-2 receptor, and complement but the levels of 7D4 by FACS were low and sometimes not above background. Differences among dendritic cells from different tissues were noted with other mAb. Adherent dendritic cells from thymus all expressed the J11d "B cell" antigen and the NL145 interdigitating cell marker, but lacked the 33D1 spleen dendritic cell antigen. Eighty to ninety percent of spleen dendritic cells were J11d-, NL145-, 33D1+ but the remainder expressed the J11d+, NL145+, 33D1- thymic phenotype. The latter phenotype also was identical to that of epidermal Langerhans' cells. We postulate that the major 33D1+ cell in spleen represents a migratory stage in which dendritic cells are moving from tissues to lymphoid organs. PMID- 2910500 TI - The effect of phorbol esters on tumor cell sensitivity to macrophage-mediated cytostasis. AB - Macrophage-mediated cytostasis was measured in a mouse syngeneic system where EL4 thymoma cells were found to be inhibited by C57B1/6 mouse macrophages. When tumor cells were pretreated with TPA, they became resistant to macrophage-mediated stasis. Nonelutriated as well as elutriated cells enriched in G1/early S and late S were sensitive to macrophage-mediated stasis. However, when elutriated cells were treated with TPA, cells enriched in G1/early S were rendered resistant to the cytostatic activity of macrophages whereas cells enriched in late S were not. The TPA effect on tumor cell susceptibility to stasis was found to be reversible and a nontumor-promoting phorbol ester, alpha-PDD, was ineffective. PMID- 2910501 TI - Kinetics of changes in peritoneal cell populations following acute inflammation. AB - The kinetics of macrophage (M phi) recruitment to the peritoneum following the induction of acute inflammation by thioglycollate broth (TG) was evaluated after prelabeling resident M phi with the fluorescent cell tracking dye, PKH-1. Most of the PKH-1-labeled resident M phi disappeared from the recoverable peritoneal cell population within the first hour after injection of TG. This disappearance coincided with the inflammatory influx of neutrophils (PMNs) and was sustained for at least 5 days after administration of TG, although the PMN number had returned to resident levels by this time. PKH-1-labeled peritoneal M phi were observed again in most animals at 7 days after injection of TG. The number of labeled M phi recovered at 7 days was approximately twice the number of resident peritoneal M phi in control animals which did not receive the TG broth. These additional M phi may include progeny of either the resident M phi or other local M phi precursors, such as omental M phi, which were labeled by the PKH-1 injection. PMID- 2910502 TI - Early human decidual cells exhibit NK activity against the K562 cell line but not against first trimester trophoblast. AB - The susceptibility of cultured first trimester human trophoblast cells to lysis by NK cells has been studied. Trophoblast cells are resistant to lysis by NK cells from both peripheral blood and decidua. However, decidual cells extracted by enzymatic disaggregation do exhibit cytotoxicity against the NK-sensitive cell line K562. The relevance of these findings to successful implantation of the blastocyst is discussed. PMID- 2910503 TI - Rat lymphokines control the migration of nonsensitized lymphocytes. AB - We investigated whether mediators released from rat splenic mononuclear cells could control the in vitro migration of nonsensitized resting rat lymphocytes. Rat splenocytes stimulated with concanavalin A, other mitogens, or histamine release three lymphokines that alter rat lymphocyte migration. A positive chemokinetic factor, termed lymphocyte chemoattractant factor (LCF), has a molecular weight (MW) between 50 and 70 kDa. Two negative chemokinetic lymphokines can also be identified; lymphocyte migration inhibitory factor (LyMIF, MW 25-45 kDa) and a high MW inhibitor (HWMI, MW greater than 70 kDa). Lymphokines were destroyed by heat as well as by treatment with neuraminidase and trypsin. The action of LCF and LyMIF was prevented by phenylmethylsulfonylfluoride, a specific serine esterase inhibitor, and the action of LyMIF was also blocked by alpha-L-fucose. The discovery of these mediators provides the opportunity to study the importance of such chemokinetic lymphokines in animal models of disease. PMID- 2910504 TI - Lymphokine-activated killer cells in rats: generation of natural killer cells and lymphokine-activated killer cells from bone marrow progenitor cells. AB - The coculture of rat bone marrow cells with recombinant interleukin-2 induced the generation of cells mediating natural killer (NK) activity and subsequent lymphokine-activated killer (LAK) activity depending upon the dose of IL-2 and time of culture. NK activity was detected as early as 4 to 5 days after the addition of IL-2 and could be evoked with as little as 5 to 50 U/ml. The induced NK cells had large granular lymphocyte (LGL) morphology and expressed 0X8 and asialo GM1 surface markers but did not express 0X19 or W3/25 markers. LAK activity was detected only after 5 days of culture, and required above 100 U/ml IL-2. Cells mediating LAK activity also expressed 0X8 and asialo GM1 but not 0X19. The generation of detectable NK and subsequent LAK activity was due to induction of early progenitor cells and not contaminating mature LGL/NK cells within the bone marrow population since of removal of such mature NK cells with L leucine methyl ester (L-LME) did not affect the subsequent generation of either activity. Moreover, the removal of actively dividing cells as well as mature NK cells from the bone marrow by treatment with 5-fluorouracil (5-FU) in vivo enriched the remaining bone marrow population for both NK and LAK progenitor cells. The phenotype of the L-LME- and 5-FU-resistant NK and LAK progenitor cells within populations of bone marrow was determined by antibody plus complement depletion analysis. Although treatment of normal bone marrow with anti-asialo GM1 + C reduced the induction of NK and LAK activity in 5-day cultures, treatment of 5-FU marrow with anti-asialo GM1 + C did not affect either activity. Treatment with a pan-T cell antibody + C did not affect the development of NK or LAK activity under any conditions. Thus, the 5-FU-resistant NK/LAK progenitors were asialo GM1 negative but became asialo GM1+ after induction by IL-2. Finally, evidence that bone marrow-derived LAK cells were generated directly from the IL-2 induced NK cells was obtained by treating the IL-2-induced LGL/NK cells with L LME.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2910505 TI - Effects of protein kinase C (PK-C) activators and inhibitors on human large granular lymphocytes (LGL): role of PK-C on natural killer (NK) activity. AB - The role of protein kinase C (PK-C) in the early metabolic events involved in human natural killer (NK) cell activation has been studied through the action of PK-C-specific activators and inhibitors. Highly purified human large granular lymphocytes (LGL) were treated for 1 hr with the diacylglycerol analog 1-oleoyl-2 acetyl glycerol (OAG) (10(-4)-10(-5) g/ml) or with 12-O-tetradecanoylphorbol-13 acetate (TPA) (10(-8)-10(-10) g/ml), both specific activators of PK-C. Both these agents consistently increased NK activity against K562 target cells. Suboptimal doses of either OAG or TPA also synergized with Ca2+ ionophores to augment spontaneous cytotoxic activity. Pretreatment of LGL with 1-(5 isoquinolinesulfonyl)-2-methylpiperazine dihydrocloride (H7) (5-40 microM), a potent PK-C inhibitor, greatly reduced NK activity in a time- and dose-dependent fashion. By contrast, N-(2-guanidinoethyl)-5-isoquinolinesulfonamide hydrochloride (HA 1004), a potent cAMP- and cGMP-dependent PK inhibitor with almost no effect on PK-C, marginally reduced NK activity. Moreover, almost complete NK activity inhibition was observed when H7 (10 microM), but not HA 1004 (50 microM), was present in the NK assay. Finally, 48 hr stimulation of LGL with TPA (10(-6) g/ml), a treatment able to inactivate most of the PK-C cellular pool, almost completely abrogated NK activity. This functional evidence was supported by phosphorylation of several endogenous substrates which occurs within 5 min in TPA-treated LGL. Two proteins of 70 and 56 kDa have been identified as major PK-C substrates, together with other phosphorylated proteins with MW ranging from 177 to 43 kDa. H7, but not HA 1004, almost completely inhibited the TPA-induced phosphorylation of all of these proteins in the NK cells. These data strongly suggest that selective activation of PK-C plays an essential role in the mechanisms of NK cell activation. PMID- 2910506 TI - Prospective evaluation of chronic cardiotoxicity due to high-dose epirubicin or combination chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil. AB - In a prospective study the left ventricular ejection fraction (LVEF), right ventricular ejection fraction (RVEF), systolic blood pressure, ECG, and heart rate were recorded at rest and during submaximal work to compare the cardiotoxic effect of epirubicin with a combination chemotherapy without known cardiotoxicity. A total of 14 females with advanced breast cancer were treated with epirubicin at a median cumulative dose of 827 mg/m2 (range, 550-1244). These patients had previously received cyclophosphamide, methotrexate, and 5 fluorouracil (CMF) or cyclophosphamide alone as adjuvant treatment, or CMF for advanced disease. The control group consisted of 11 females with advanced breast cancer given CMF only. The systolic blood pressure at rest as well as during submaximal work was significantly lower (P less than 0.05) after treatment in the epirubicin group than in the CMF controls. With regard to LVEF, the median value of 54% at rest was significantly lower after treatment in the epirubicin group than in the controls (59%). There was a significant fall in LVEF at rest and during exercise in the epirubicin group, whereas no such changes were found in the CMF controls after treatment. The RVEF was unaffected. In the epirubicin treated group one patient developed fatal congestive heart failure, and in the remaining 13 patients treatment was discontinued due to progression of the cancer and not to cardiotoxicity. Thus, the cardiotoxicity of epirubicin changed the clinical outcome in only 1 of 14 patients with advanced breast cancer. PMID- 2910507 TI - Enhanced cutaneous radiation effects following high-dose busulfan therapy. AB - Fifteen patients received irradiation after combined chemotherapy with high-dose busulfan followed by autologous or allogeneic bone marrow transplantation. Of nine patients irradiated between day 30 and day 70 after their engraftment, seven developed an increased radiation response in the skin: four showed enhanced reactions during irradiation, and three had a total or severe definitive alopecia more than 16 months after CNS irradiation. Six patients were irradiated after day 70; they had either normal reactions or none at all within the cutaneous radiation portals. The possibility that busulfan might be a radiosensitizer is raised. PMID- 2910508 TI - A new anticancer agent (LY186641) interferes with creatinine assay. AB - The administration of a diarylsulfonylurea, LY186641, which is presently undergoing a multicentric phase I clinical trial as an anticancer agent, produces major analytical interference with commonly used creatinine analysis techniques. We confirm that this interference is caused by a metabolite rather than the parent compound and propose an alternative, interference-free method. PMID- 2910509 TI - Fanconi syndrome after ifosfamide. AB - A 2-year-old boy developed the Fanconi syndrome 1 year after being treated successfully for a neuroblastoma. This is probably an unusual complication of ifosfamide. PMID- 2910510 TI - Phase II study of a new alkylating agent (PTT-119) in resistant-relapsed non Hodgkin's lymphomas. AB - In a phase II study we evaluated the effect and toxicity of a new alkylating agent, PTT-119, in 26 patients with non-Hodgkin's lymphomas (NHL) resistant to or relapsed after other chemotherapy. PTT was scheduled by escalating the dose from 2.0 to 3.3 mg/kg every 3 weeks. Among 21 evaluable patients with NHL, 12 (57%) showed a good response (CR + PR) to PTT-119. Tolerance was acceptably good; no major side effects related to liver, cardiac, or renal toxicity were recorded. The most commonly recorded side effects were nausea and vomiting, alopecia, and phlebitis; diarrhea and drug-related fever were rarely seen. This report indicates a potential usefulness for PTT-119, a non-cross-resistant alkylating agent, in the treatment of NHL. PMID- 2910511 TI - Failure of response to ifosfamide in squamous cell bronchogenic carcinoma. PMID- 2910512 TI - Evaluation of response to chemotherapy in retinoblastoma heterotransplanted to the eyes of nude mice. AB - The role of chemotherapy in the treatment of retinoblastoma (RB) is unsatisfactory and clinical research is severely limited. A xenograft model for testing chemotherapeutic and other agents has been developed by the heterotransplantation of human RB cells into the anterior chamber of the nude mouse eye. A grading system for visually monitored tumor growth was designed to allow serial observations and documentation of the response to therapy in the model. This method of monitoring compared favorably with histopathologic, photographic, or other criteria in the reproducible, sequential evaluation of tumor status. Six chemotherapeutic agents [vincristine (VCR), doxorubicin (DOX), actinomycin D (ACT-D), dimethyltriazeno-imidazole carboxamide (DTIC), cyclophosphamide (CPM), and diaziquone (AZQ)] were then tested in the model against a patient-derived xenograft line. Results were expressed as the delay in tumor progression judged by serial grading. CPM produced a consistent response in all treated tumors, as did DTIC to a lesser, more variable extent. In 3 of 10 tumors treated with CPM and in 1 of 18 treated with DTIC, complete responses were maintained for at least 20 weeks. VCR, DOX, and ACT-D were ineffective, producing patterns of tumor progression no different from those in the control group. AZQ was most effective, producing responses far exceeding those of conventional agents. The model allows quantitative documentation of the response to therapy in heterotransplanted human RB. Further testing of new agents and combinations is warranted. AZQ may be active against RB. PMID- 2910513 TI - Tumor and serum tamoxifen concentrations in the athymic nude mouse. AB - The athymic nude mouse has been used as an in vivo model for pharmacologic studies of the antiestrogen, tamoxifen. Serum and tumor tamoxifen and metabolite concentrations were examined during and after 100 and 1000 micrograms/day doses injected s.c. Tamoxifen and tamoxifen metabolites were quantitated by high performance liquid chromatography. Tamoxifen was detected in tumors after a dose of 100 micrograms/day, although serum concentrations were not detected. At a dose of 1000 micrograms/day, tumor tamoxifen and its active metabolites were detected in high concentrations ranging up to greater than 6 mmol/g tissue. Serum tamoxifen metabolites were not detected at either dose. In summary, high doses of tamoxifen were required in the nude mouse to obtain clinically relevant serum concentrations, and significant tumor levels were achieved at doses that resulted in undetectable serum levels. The relationship between serum tamoxifen concentrations, tumor tamoxifen levels, and the biologic activity of the drug requires further study. PMID- 2910514 TI - Neurotoxicity and dermatotoxicity of cyanomorpholinyl adriamycin. AB - The highly lipophilic cyanomorpholinyl adriamycin (CMA) is the most potent antineoplastic anthracycline yet described. CNS distribution and toxicity were examined after i.v. administration of CMA to mice. At doses greater than or equal to 0.1 mg/kg, a neurotoxic syndrome including ataxia, hypokinesia, and tremors appeared. At doses of less than or equal to 0.05 mg/kg, which have been reported to be antineoplastic, no neurotoxicity was observed. On histopathologic examination, no changes were observed in the brain, spinal cord, or dorsal root ganglia. Unlike adriamycin (ADR), which rapidly appears in the nuclei of several tissues, CMA showed no fluorescence, suggesting a different cellular microcompartmentalization. The i.d. injection of CMA disclosed a 200-fold increase in toxicity compared with that of adriamycin. In comparisons of CMA and ADR, neurotoxicity and cardiotoxicity occurred equally only at higher doses; however, the dermatotoxicity and antineoplastic activity of CMA were increased several hundred-fold. PMID- 2910515 TI - Relevance of the hydrolysis and protein binding of melphalan to the treatment of multiple myeloma. AB - Experiments to determine the hydrolysis and protein binding of melphalan (L phenylalanine mustard, L-PAM) were carried out in vitro for therapeutic concentration of the drug: the decrease in L-PAM concentration in plasma and whole blood during 24 h incubation at 37 degrees C was only 5% due to hydrolysis. Serum protein binding was about 90%, whereby 60% and 20% of this binding was due to interactions with albumin and acid alpha 1-glycoprotein, respectively. Immunoglobulins did not participate in the binding of L-PAM. The covalently bound part of L-PAM in serum was 30% in the concentration range of 1-30 micrograms/ml. The binding of dihydroxymelphalan (DOH) in serum did not exceed 20%. Glucocorticoids used in combination with L-PAM for treating multiple myeloma did not influence its protein binding. Our study with 35 sera from 15 patients with multiple myeloma shows that high levels of paraproteins do not increase but may decrease the binding of L-PAM, resulting in an elevated concentration of free drug. PMID- 2910517 TI - High-dose melphalan dosage adjustment: possibility of using a test-dose. AB - Previous pharmacokinetic studies of i.v. high-dose melphalan (HDM) have demonstrated large interindividual variations in the pharmacokinetic parameters. We therefore studied the possibility of using a test dose of the drug to determine the level of a subsequent therapeutic dose. This study was undertaken to establish whether the pharmacokinetics of melphalan were linear and reproducible within the same patient and determine whether a linear extrapolation could be carried out from the test dose. The first eight patients were studied on two occasions separated by 2 hours (repeatability stage). Although reasonable evidence for linear pharmacokinetics was obtained from these patients, the data suggested a number of factors that might have introduced errors. Therefore, the second group of ten patients were treated on a slightly different protocol on two occasions 24 h apart (linearity stage). The ratios of the two doses ranged from 1 to 8 (repeatability stage) and from 2.6 to 10 (linearity stage). During both stages there was a good correlation between the AUC measured for the second infusion and that predicted from the first (r = 0.929 and r = 0.943, respectively). We conclude that a test dose can be used to determine the subsequent dose of melphalan necessary to produce a desired AUC. PMID- 2910516 TI - In vitro evidence for dose-dependent cytotoxicity as the predominant effect of low dose Ara-C on human leukemic and normal marrow cells. AB - To determine whether cytosine arabinoside (Ara-C) has a differentiating effect in vitro, marrow cells from nine patients with acute non-lymphocytic leukemia or myelodysplastic syndrome and eight non-leukemic controls were exposed to drug concentrations comparable to those achieved in vivo with low-dose Ara-C therapy. In soft agar cultures, the predominant effect of Ara-C at concentrations between 10(-8) M and 10(-6) M was cytotoxicity with a dose-dependent decrement in Colony Forming Unit of the granulocyte and monocyte lineage (CFUg/m) at 14 days. Growth in liquid cultures containing Giant Cell Tumor(GCT)-conditioned media without Ara C resulted in a significant increment in the recovery of mature cells at day 10 from the non-leukemic cultures (P = 0.03), while only a minor increase was found in the leukemic cultures (P = 0.09). All liquid cultures exposed to greater than or equal to 10(-9) M Ara-C showed a marked reduction in the immature proliferating cell pool, with a concomitant increase in the percentage of mature non-dividing cells at 10 days. However, the absolute number of differentiated cells recovered remained constant or decreased in all non-leukemic and eight of nine leukemic cultures, compared with cultures without Ara-C. Enhanced recovery of differentiated cells was also never observed in any culture exposed to the relatively non-toxic 10(-9) M Ara-C. These in vitro findings support clinical observations suggesting that cytotoxicity rather than differentiation is the major mechanism involved in the therapeutic effect of low-dose Ara-C in acute leukemia and myelodysplasia. PMID- 2910518 TI - The effects of acetaminophen, antipyrine and phenacetin on rat urothelial cell proliferation. AB - Abuse of combination analgesics containing phenacetin, antipyrine (phenazone) and caffeine have been associated with urinary tract tumors. Phenacetin and antipyrine have been shown to be promoters of urinary tract carcinogenesis and antipyrine is also a weak urinary tract carcinogen. Acetaminophen, the main metabolite of phenacetin, is one of the most commonly used analgesics in the USA. In the present study, the dose-related effect on the cell proliferation of the urothelium was evaluated in male Sprague-Dawley rats by autoradiography. Nine groups of twenty, 6-week old rats were treated with 0.5%, 1.0% or 1.5% of acetaminophen, antipyrine or phenacetin in the diet. A tenth group of rats received control diet without added chemicals. Ten rats from each group were killed after each of 6 and 12 weeks of feeding. There was a dose-related increase in the labeling index in the urothelium of the bladder and kidney, particularly after 6 weeks of drug administration. In particular, the 1.0% and 1.5% dose levels of antipyrine and phenacetin showed a marked proliferative effect on the urothelium. In the bladder after 6 weeks, the labeling indices were significantly increased. After 12 weeks, although numerically increased, the indices were not statistically significant. In the renal pelvic urothelium the labeling index was significantly increased in antipyrine and phenacetin treated rats at doses of 1.0% and 1.5%. After 12 weeks the majority of rats treated with 1.5% antipyrine and phenacetin had labeling indices greater than or equal to 2-fold than the control rats both in the kidney and bladder. The increased labeling indices were associated with urothelial hyperplasia, in particular after 6 weeks. In the rats treated with antipyrine there were significant degenerative changes in the urothelial cells expressed as marked vacuolization. The vacuolization is considered to be a toxic effect and the beginning of cell death. Thus cell death with regeneration may be responsible for the increased labeling index in the antipyrine groups. High doses of antipyrine were also associated with renal papillary necrosis in 50% of the rats. PMID- 2910519 TI - Effect of growth state, tumor promoters, and transformation upon intercellular communication between C3H/10T1/2 murine fibroblasts. AB - Diminished intercellular communication has been associated with heightened sensitivity of cultured cells to morphological transformation and enhancement of transformation by tumor promoters. Microinjection of Lucifer yellow dye was employed to evaluate intercellular communication between transformable C3H/10T1/2 murine fibroblasts under a variety of culture conditions. Intercellular communication assayed by dye transfer from injected cells to surrounding cells in contact occurred in logarithmically growing cultures, declined to very low levels as confluence was attained, and then resumed upon the formation of mature confluent monolayers. Dye-transfer networks of 50 or more cells resulted from injection of single monolayer cells. Freeze-fracture electron microscopy confirmed the presence of gap junction structures in confluent cultures. Treatment with the initiating agent N-methyl-N'-nitro-N-nitrosoguanidine and/or the tumor promoter 2,3,7,8-tetrachlorodibenzo-p-dioxin did not inhibit intercellular communication between C3H/10T1/2 cells during 6-week transformation experiments. The tumor promoter 12-O-tetradecanoylphorbol-13-acetate produced a transient inhibition of dye-coupling upon first introduction to cultures and prolonged the period of diminished dye-coupling at the attainment of confluence, but did not inhibit subsequent interactions between monolayer cells. A simple relationship thus could not be established between levels of dye-coupling within monolayers and focus formation events. Curiously, although the cells of foci in early phases of development did not exhibit dye-transfer capacity, dye-coupling was observed in mass cultures of most transformed cell lines cloned from foci. Co cultivation of communication-competent transformed cells with nontransformed cells to produce reconstructed foci generally resulted in a cessation of dye transfer by transformed cells. An often reversible loss of communication competence thus accompanies the growth of transformed C3H/10T1/2 cells as foci and may constitute an adaptive response which facilitates focus growth in the presence of intercellular communication between monolayer cells. PMID- 2910520 TI - Tobacco-specific nitrosamines in mainstream smoke of West German cigarettes--tar alone is not a sufficient index for the carcinogenic potential of cigarette smoke. AB - Fifty-five types of commercial cigarettes on the West German market were analyzed for tobacco-specific nitrosamines (TSNA) in mainstream smoke. The cigarettes included filter and nonfilter cigarettes with very high, high, medium, low and ultra-low tar and nicotine yields. The observed range for N'-nitrosonornicotine was from 5 to 625 ng/cigarette and for 4-(methylnitrosoamino)-1-(3-pyridyl)-1 butanone from not detected (less than 4 ng/cigarette) to 432 ng/cigarette. The highest TSNA values were obtained for nonfilter cigarettes made of dark tobaccos and the lowest values for nonfilter Oriental-type cigarettes. Relatively high TSNA yields were also observed in filter cigarettes with moderate and lower tar deliveries. The results demonstrated that there is no correlation between TSNA and tar deliveries in mainstrain smoke. The TSNA deliveries in mainstream smoke depended on the actual tobacco composition. According to these results the tar delivery, although crucial, is not a sufficient index for the biological activity and the carcinogenic potential of cigarette smoke. PMID- 2910521 TI - Promotion by sodium barbital of renal cortical and transitional cell tumors, but not intestinal tumors, in F344 rats given methyl(acetoxymethyl)nitrosamine, and lack of effect of phenobarbital, amobarbital, or barbituric acid on development of either renal or intestinal tumors. AB - Comparative effects of four barbiturates, phenobarbital (PB), amobarbital (AB), sodium barbital (NaBB), and barbituric acid (BA) on the development of neoplasms in the intestinal tract and other organs were investigated in rats following initiation with methyl(acetoxymethyl)nitrosamine (DMN-OAc). Four-week-old F344/NCr male rats were given a single i.p. injection of 0.05 nmol DMN.OAc in 5 ml sterile phosphate buffered saline/kg body weight. Two weeks after DMN.OAc treatment, the animals were provided with either tap water or drinking water containing 500 p.p.m. of PB, NaBB, AB, or BA for the remaining experimental period. Control groups received a single i.p. injection of 5 ml of sterile phosphate buffer/kg body weight and 2 weeks later were given either tap water or drinking water containing 500 p.p.m. of one of the barbiturates listed above. Rats were killed at 52 weeks or 80 weeks after DMN.OAc injection. DMN.OAc induced multiple intestinal tumors that occurred mostly in the mucosa of the small intestine, especially the terminal ileum. None of the barbiturates had any effect on either incidence or multiplicity of intestinal tumors. PB significantly enhanced the development of hepatocellular tumors as well as thyroid follicular cell neoplasms in DMN.OAc initiated rats, while the subsequent administration of NaBB, but not other barbiturates, resulted in the development of renal cortical and pelvic transitional cell tumors. This is the first demonstration of promotion of carcinogenesis in renal pelvic transitional epithelium, a cell type not previously recognized as vulnerable to initiation by DMN.OAc given i.p. NaBB without prior administration of DMN.OAc induced severe nephropathy and focal hyperplasia of both renal cortical tubular and pelvic transitional cell epithelium. No such effects were observed with either PB, AB, or BA. Our results failed to confirm the earlier findings of others that intestinal epithelial carcinogenesis could be promoted by continuous oral administration of NaBB. However, these results strongly support and extend our previous conclusions that some barbiturates have broad organ specificities and promote epithelial carcinogenesis in more than one organ and tissue. PMID- 2910522 TI - Tumor promoting activities of ethylphenylacetylurea and diethylacetylurea, the ring hydrolysis products of barbiturate tumor promoters phenobarbital and barbital, in rat liver and kidney initiated by N-nitrosodiethylamine. AB - The ring hydrolysis products of the multi-tissue tumor promoting barbiturates, phenobarbital (PB) and barbital (BB), were fed to F344/NCr male rats previously given a single initiating injection of N-nitrosodiethylamine. Ethylphenylacetylurea (EPAU) and diethylacetylurea (EEAU), derived, respectively, from PB and BB, both promoted development of hepatocellular adenomas, but were much weaker in this respect than PB. Both acetylureas were also selective inducers of P-450IIB1-mediated benzyloxyresorufin O-dealkylase activity, but both were much less potent inducers than PB. Neither EPAU nor EEAU had an effect on tumor development in the thyroid, unlike both PB and, as shown previously, BB. EEAU, but not EPAU, strongly promoted development of renal cortical epithelial tumors. The opening of the barbiturate heterocyclic ring and the subsequent decarboxylation to yield the dialkylacetylurea analogs thus resulted in compounds displaying a marked reduction in liver tumor promoting activity. EEAU appears to possess an ability to promote renal neoplasms similar to that of its parent compound, BB. Ring opening appears to be accompanied by loss of promoting activity for thyroid follicular epithelium. PMID- 2910523 TI - 32P-postlabeling analysis of 1-nitropyrene-DNA adducts in female Sprague-Dawley rats. AB - The 32P-postlabeling technique was used to qualitatively establish the pattern of DNA adduct formation in mammary tissue and liver following administration of 1 nitropyrene to female Sprague-Dawley rats. 1-Nitropyrene (100 mg/kg b.w.) was administered by gavage in trioctanoin and the rats were sacrificed 24 h later. DNA was isolated from mammary fat pads and liver, enzymatically hydrolyzed to deoxyribonucleoside-3'-monophosphates and then converted to [5'-32P]3',5' bisphosphates. The polyethyleneimine-cellulose (PEI-cellulose) TLC 32P fingerprints revealed the presence of multiple putative adducts in the mammary fat pads and in the livers. To investigate the role of nitroreduction in the formation of these adducts, calf thymus DNA was incubated with [3H]1-nitropyrene in vitro in the presence of xanthine oxidase. The DNA was isolated and analyzed by the 32P-postlabeling technique. A major adduct spot was detected and confirmed as N-(deoxyguanosin-8-yl)-1-aminopyrene. This adduct cochromatographed with a minor in vivo adduct of DNA obtained from mammary fat pads and livers. However, the major adducts detected in vivo did not appear to originate from simple nitroreduction of 1-nitropyrene. The results of this study suggest that other metabolic pathways, such as ring oxidation, or ring oxidation followed by nitroreduction, may be responsible for the putative 1-nitropyrene-DNA adducts observed in mammary fat pads and livers of female Sprague-Dawley rats. PMID- 2910524 TI - Neuroendocrine dysdifferentiation and bombesin production in carcinogen-induced hepatocellular rat tumours. AB - Primary rat hepatocellular tumours, induced by a combination of diethylnitrosamine and 2-acetylaminofluorene, were examined for the presence of neuroendocrine peptides by immunocytochemical methods. Two-thirds of the tumours showed positive immunostaining for either neuron-specific enolase (NSE), protein S-100 or bombesin. NSE was commonly observed both in hepatocarcinomas and in neoplastic nodules, whereas protein S-100 was more frequently seen in carcinomas (49% positive) than in nodules (13% positive). Bombesin, previously shown to function as an autocrine growth factor in small-cell carcinoma of the lung, was present in neurosecretory granules in 13% of the nodules and 29% of the carcinomas. Normal, preneoplastic and peritumorous liver tissue, including the frequent atypical foci present in the latter two categories, was uniformly negative for all neuroendocrine markers. The foci, like the nodules and carcinomas, generally stained positively for the liver tumour marker glutathione S-transferase type P (GSTP). The results suggest that dysdifferentiation of altered hepatocytes in a neuroendocrine direction may be a common, late event in liver carcinogenesis which could possibly contribute to tumour formation, e.g. by establishing autocrine or paracrine circuits. PMID- 2910525 TI - The initiator tRNA acceptance assay as a short-term test for carcinogens. 4. Results with 20 mycotoxins. AB - The activity of 20 mycotoxins was tested by the recently developed initiator tRNA acceptance assay for carcinogens. With the exception of citrinin, all compounds carcinogenic for rodents stimulated the charging of tRNA with L-methionine. In three out of four non-carcinogenic mycotoxins the test was negative. Five carcinogenic mycotoxins were negative in mutagenicity tests but positive in the acceptance assay indicating that also non-mutagenic carcinogens may be detected by the latter procedure. PMID- 2910526 TI - Concomitant reversion of the characteristic phenotypic properties of a cell line of Bloom's syndrome origin. AB - The fibroblast strain GM3498 and the lymphoblastoid line GM4408 have been established from the same Bloom's syndrome patient, as confirmed by DNA hybridization with hypervariable probes and isoenzyme analysis. Strain GM3498, but not GM4408, exhibits a high frequency of spontaneous sister chromatid exchange, hypersensitivity to ethyl methanesulphonate and an anomalously low level of DNA ligase I activity. We conclude that GM3498 is representative of Bloom's syndrome, whereas GM4408 is a revertant cell line. These data agree with a model in which a malfunctioning DNA ligase I is the primary cause of the syndrome. PMID- 2910527 TI - In vivo distribution of a carcinogenic hepatic peroxisome proliferator: whole body autoradiography of [14C]ciprofibrate in the mouse. AB - The distribution of radiolabel in male mice was studied by whole-body autoradiography at intervals after oral administration of [14C]ciprofibrate, a carcinogenic hepatic peroxisome proliferator. Radioactivity was rapidly taken up by the liver and to a lesser extent by the brown fat within 9 h after oral dosing of ciprofibrate. The radioactivity levels in blood, interstitial fluid and fat decreased during the first 3 days after dosing, but the liver remained densely labeled. Between 3 and 27 days after dosing, liver exhibited a stippled pattern as a result of heavier labeling apparently around the central veins. The relatively low levels of radiolabel in extra-hepatic tissues observed after oral dosing, together with the prolonged retention in this region of the liver, is consistent with the hepatotropic effects (i.e. hepatic peroxisome proliferation and development of liver tumors) exerted by this compound. PMID- 2910528 TI - Molecular mechanics simulations on covalent complexes between polycyclic carcinogens and B-DNA. AB - We present molecular mechanics simulations on models of covalent complexes between the diol-epoxides of the carcinogens benzo[a]pyrene, benzo[e]pyrene and benzo[c]phenanthrene and a DNA pentamer d(GCGCG).d(CGCGC). In all the models, the carcinogen diol-epoxides lie in the minor groove with alkylation to the exocyclic amino group of the guanine. The theoretical calculations on the benzo[a]pyrene adducts to the pentamer are qualitatively consistent with the experimentally observed relative reactivities between various isomers. The adduct with the (+)trans isomer, which is the most carcinogenic of the benzo[a]pyrene stereoisomers, is calculated to be the energetically most favored. The relative energetic preferences in the adducts of benzo[e]pyrene diol-epoxides to the pentanucleotide parallel those of benzo[a]pyrene. However, there is no obvious explanation for the lack of biological activity in the diol-epoxides of the former carcinogen from the theoretical calculations. In the case of adducts with the diol-epoxides of benzo[c]phenanthrene, the energetically most favored structures are isomers with significant biological activity. The distortions in the double helix are more significant in the complexes with the diol-epoxides of this carcinogen compared to those in the complexes with the diol-epoxides of the other two carcinogens. PMID- 2910529 TI - Unsaturated lipids and intestinal bacteria as sources of endogenous production of ethene and ethylene oxide. AB - Studies of adducts to hemoglobin (Hb) have revealed levels of hydroxyethylations of i.a. N-terminus (valines) in knowingly unexposed animals and persons (non smokers). This paper describes some exploratory experiments with mice, carried out with the aim of tracing the origin of these background levels. It is shown that the hydroxyethylvaline content in Hb is higher in animals fed unsaturated lipids and lower in bacterium-free as compared to control animals. Lipid peroxidation and metabolism of intestinal bacteria, giving rise to ethene, precursor of ethylene oxide, are thus indicated to be sources of observed background hydroxyethylations. PMID- 2910530 TI - Detection by 32P-postlabeling of thymidine glycol in gamma-irradiated DNA. AB - The 32P-postlabeling method has been adapted for the analysis of thymidine-cis glycol-3'-phosphate (cis-dTGp,cis-5,6-dihydroxy-5,6-dihydrothymidine-3'-phosphat e). Cis-dTGp was isolated and purified from normal nucleotides by phenylboronate affinity chromatography and phosphorylated by T4 polynucleotide kinase in presence of 1 mM BeCl2 at pH 7.5. These modifications of the postlabeling method resulted in a 5'-phosphorylation of dTGp with a labeling efficiency of up to 20% whereas the natural nucleotides were almost completely dephosphorylated at the 3' position under these conditions. The reaction products, containing radio-labeled thymidine-cis-glycol-3',5'-bis-[5'-32P]phosphate (cis-*pdTGp), were separated by two-dimensional anion-exchange TLC on polyethyleneimine cellulose sheets. Boric acid was added in the second dimension in order to selectively retard cis glycols. The method was applied to gamma-irradiated nucleotides and calf thymus DNA. In the nucleotide mixture, 330-99,000 thymine glycol (TG) moieties were detected per 10(6) thymines (T) in a dose range of 14-1000 Gy respectively. In DNA, these values ranged from 400 to 2700 TG/10(6) T. The data are in good agreement with methods using radiochemical and immunological techniques. Non irradiated DNA showed a background level of 10TG/10(6) T. This practical limit of detection was higher than can be achieved with the postlabeling technique, indicating that the present method might be a sensitive alternative for a determination of oxidative DNA damage. PMID- 2910531 TI - Structure-activity studies of chemical carcinogens: use of an electrophilic reactivity parameter in a new QSAR model. AB - Electrophilic reactivity data for 142 compounds were obtained from the literature, and were used to establish the contribution of different functional groups and molecular determinants to this property. An equation containing approximately 20 molecular determinants was derived (r = 0.89); this provided a system for estimating the electrophilic reactivity for other compounds on the basis of their molecular structure. The contribution of the estimated electrophilicity to the structure-activity relationship (SAR) studies of carcinogens was tested. In a previous work, we studied a set of 137 carcinogens and non-carcinogens belonging to different chemical classes, and established an SAR on the basis of four physical-chemical descriptors. The mathematical model consisted of a pattern recognition method specifically designed by us for the non linear situations typical of large non congeneric sets of chemicals. The addition of the estimated electrophilicity parameter increased the overall performance of the system (from the previous 85-90% retrospective correct classification). In particular, the estimated electrophilicity remarkably contributed to the identification of carcinogens (their correct classification increasing from the previous 86% to 97%). The derived SAR was tested by applying it to 11 human carcinogens not included in the training set. Their carcinogenicity was correctly predicted for 10 chemicals out of 11. PMID- 2910532 TI - Variations in catechol O-methyltransferase activity in rodent tissues: possible role in estrogen carcinogenicity. AB - Catechol-O-methyltransferase (COMT) [EC 2.1.1.6] is a ubiquitous cytosolic enzyme which has a pertinent role in the inactivation of both natural and synthetic catechol estrogens in mammalian tissues. We have compared the COMT activity in mouse, hamster and rat kidney, liver and red blood cells and examined the kinetic characteristics of this enzyme in the latter two species using various catechol estrogens as substrates. Results presented here indicate that the ratios of COMT activity in the kidney versus the liver of the rat and mouse are nearly identical, 0.48-0.52, whereas there is a 29-fold ratio between the level of COMT activity in these two tissues in the hamster. In red blood cells, the level of COMT activity is 4- and 12-fold lower in the hamster compared to mouse and rat, respectively. When the kinetic characteristics of this enzyme were assessed in the hamster and rat kidney and liver, except for 2-hydroxymoxestrol which had an apparent Km value of 15-48 microM, the other catechol estrogen substrates exhibited Km values ranging from 1-10 microM. Generally, the Vmax values were markedly higher in the rat kidney and liver than those observed in corresponding hamster tissues. The significantly lower COMT activity in the hamster liver and red blood cells suggests that under chronic estrogen treatment at high doses, the concentration of catechol estrogens in these tissues may exceed the capacity of COMT to effectively catalyse their O-methylation into inactive metabolites. The resulting accumulation of catechol estrogens may contribute to the estrogen carcinogenicity observed in the hamster liver and kidney. Additionally, when 2 hydroxyestrone was used as a substrate, the estrogen-induced renal carcinoma exhibited only 8.6% of the COMT activity found in the normal kidney. PMID- 2910533 TI - Induction of rat intestinal carcinogenesis with single doses, low and high repeated doses of 1,2-dimethylhydrazine. AB - We investigated seven different procedures for chemical induction of rat colonic carcinogenesis using: repeated high doses (i) weekly 10 x 15 mg/kg, (ii) quarterly 8 x 15 mg/kg; repeated low doses (iii) weekly 27 x 1.5 mg/kg, (iv) quarterly 8 x 5 mg/kg, (v) quarterly 8 x 1 mg/kg; and single injections of 1,2 dimethylhydrazine (DMH) at (vi) 1 x 40 mg/kg or (vii) 1 x 20 mg/kg. Rats had typical histological precancerous lesions of the colon (dysplasia) and intestinal carcinomas in the six groups receiving a total dose of more than 8 mg/kg DMH. With doses of greater than 120 mg/kg, rats had more cancers, particularly intestinal carcinomas and significantly reduced survival. Rats receiving a single injection of 20 or 40 mg/kg also had histological lesions and colonic carcinomas. The group receiving a 40 mg/kg total dose in a single injection had a significantly higher frequency of colonic lesions per rat and a higher incidence of rats with colonic lesions than groups receiving the same total dose but fractionated. Control rats and groups injected with an 8 mg/kg total dose had no cancers, nor pre-cancerous histological lesions. Thus the carcinogenesis is dose related, but for the same final dose a single injection gives more histological colonic lesions than several recurrent injections; however, the number of colonic carcinomas and the survival did not vary. This lack of correlation between the number of dysplasia and the number of adenocarcinomas may indicate that dysplasia is not always the precursor lesion of adenocarcinoma. With repeated low doses, we obtained colonic adenocarcinomas after a long period of latency in old rats, thus producing an experimental model with characteristics similar to those found in humans. PMID- 2910534 TI - An endogenous colon mitosis inhibitor reduces the increased cell proliferation in colonic epithelium induced by dietary cholic acid and treatment with 1,2 dimethylhydrazine. AB - We have recently purified and identified a tripeptide (pGlu-His-GlyOH) in mouse intestinal extracts which reversibly inhibits normal colonic epithelial cell renewal in mice. We also found a similar response to a single injection of the peptide during bile-acid-induced hyperproliferation in the colonic epithelium. To investigate the effect of repeated injections of the same dose of the inhibitor under various pathological conditions of the colonic mucosa we either fed mice low-calcium cholic acid diet, treated the animals with a single injection of the colon carcinogen 1,2-dimethylhydrazine (DMH), or gave both treatments. The peptide reduced the mitotic rate and the labelling indices in the colonic epithelium during the first 5 days of feeding the low-calcium cholic acid diet, and the size of the proliferative compartment was reduced. Proliferating cells were found significantly closer to the base of the crypts in the peptide-treated animals. The mitotic rate was also reduced by each of repeated peptide injections during the first 72 h in the DMH-treated animals; the labelling indices at 48 and 72 h only. By feeding DMH-treated animals low-calcium cholic acid diet, similar results were obtained. However, in all carcinogen-treated animals the tripeptide had no effect on the size and localization of the proliferating cells in the colonic crypts. PMID- 2910535 TI - Cyclophosphamide induced DNA strand breaks in mouse embryo cephalic tissue in vivo. AB - Pregnant C3H mice were exposed to teratogenic doses of cyclophosphamide (CPA), on the 11th day after copulation. The effects of this agent on embryonal cephalic DNA strand breaks were assessed between 3 and 40 h after drug administration. Administration of 15, 30 and 60 mg CPA/kg body weight resulted in conversion of 23, 30 and 44% of the DNA to the single-stranded form, respectively. No detectable DNA damage was evident 3 h after drug administration, but after 6 h significant DNA damage had occurred, reaching a maximum after 9 h. However, no evidence of DNA strand breaks was present at 22, 30 and 40 h after CPA treatment, suggesting that these lesions had been repaired. These findings demonstrate that cephalic DNA damage induced by CPA in the developing mouse embryo occurs in a time and concentration dependent manner, and provide some insight into the kinetics of formation and removal of DNA strand breaks caused by CPA in vivo. PMID- 2910536 TI - Eicosanoids and multistage carcinogenesis in NMRI mouse skin: role of prostaglandins E and F in conversion (first stage of tumor promotion) and promotion (second stage of tumor promotion). AB - When applied to NMRI mouse skin in vivo, phorbol esters such as 12-O tetradecanoylphorbol-13-acetate (TPA) and 12-O-retinoylphorbol-13-acetate (RPA) have been found to induce two early waves of prostaglandin E2 (PGE2) synthesis after 15 and 90 min and a delayed accumulation of prostaglandin F2 alpha (PGF2 alpha) after 2 h. With respect to PGF2 alpha formation different activities of both agents were observed, in that TPA but not RPA induced additional PGF2 alpha waves after 4 and 17 h. Functionally, PGE2 was previously shown to be an endogenous mediator of the TPA- or RPA-induced epidermal hyperproliferation and hyperplasia. A functional role of PGF2 alpha could be attributed to the post initiation stages of tumor development in initiated mouse skin, i.e. the conversion stage (stage I of tumor promotion) elicited by two TPA applications and the promotion stage (stage II of promotion) brought about repetitive RPA treatments. PGF2 alpha, appearing as one distinct biosynthetic wave 3-4 h after TPA application seems to be critically involved in the conversion steps since (i) inhibition of its accumulation by indomethacin led to an inhibition of tumor formation, (ii) the inhibitory effect of indomethacin could be reversed by PGF2 alpha and (iii) RPA was not able to give rise to the accumulation of PGF2 alpha 4 h after application as obtained by TPA treatment. Moreover, RPA-induced promotion of DMBA- and TPA-treated mouse skin was inhibited by indomethacin. The inhibitory effect of indomethacin on papilloma formation was again reversed by PGF2 alpha treatment concomitant with RPA. PMID- 2910537 TI - Reactions of stereoisomeric non-bay-region benz[a]anthracene diol epoxides with DNA and conformations of non-covalent complexes and covalent adducts. AB - The reactions of the non-bay-region diol epoxides racemic trans-8,9-dihydroxy anti-10,11-epoxy-8,9,10,11-tetrahydrobenz[a]an thracene (anti-BA-10,11-DE) and racemic trans-8,9-dihydroxy-syn-10,11-epoxy-8,9,10,11-tetrahydrobenz[a]ant hracene (syn-BA-10,11-DE) with native double-stranded DNA in aqueous solutions (5 mM sodium cacodylate buffer, pH 7.0, 23 degrees C) was investigated utilizing various spectroscopic techniques. The results of linear dichroism experiments suggest that both diastereomers form non-covalent, intercalative complexes with DNA prior to undergoing chemical reactions; the association constant for the anti stereoisomers is about twice as large (850 +/- 100 M-1) as that for the syn diastereomers, thus qualitatively paralleling the behavior established previously for the bay-region diol epoxides of benzo[a]pyrene and benz[a]anthracene. The reaction rates of both anti- and syn-BA-10,11-DE are significantly accelerated in the presence of DNA, and the fraction of diol epoxide molecules which bind covalently to DNA is 13 +/- 2% and 3 +/- 1% respectively; these levels of covalent binding are lower by factors of about two respectively, than in the case of the bay-region diol epoxides of benz[a]anthracene. The phenanthrenyl residues in the covalent anti-BA-10,11-DE-DNA adducts are tilted with their long axes closer to the average orientations of the normals to the DNA bases; in contrast, the adducts derived from the binding of the syn diastereomers, appear to be characterized by intercalative-type conformations; however, the overall degrees of orientations are weak in the cases of these non-bay-region diol epoxide-DNA adducts. Nevertheless, these adduct conformations resemble those derived from the highly tumorigenic anti and the less active syn diasteromers of benzo[a]pyrene and benz[a]anthracene, thus providing one additional example to the previously observed correlations between adduct structure and biological activity. PMID- 2910538 TI - Transcardiac serotonin concentration is increased in selected patients with limiting angina and complex coronary lesion morphology. AB - Serotonin is released by activated platelets and may act as a mediator to initiate or sustain certain unstable syndromes of ischemic heart disease in humans. To determine whether or not serotonin concentration increases across the coronary bed in patients with severe, limiting angina, we measured central aortic and coronary sinus serotonin concentrations by a sensitive radioenzymatic assay in 39 patients with coronary artery disease and 13 patients with minimal or no coronary artery lesions as detected by arteriography. Although no difference existed in the mean aortic or coronary sinus serotonin concentrations between these two groups, elevated coronary sinus serotonin concentrations were detected in 23% of those with coronary artery disease. The coronary sinus and aortic serotonin concentration difference was greater in patients with significant coronary artery disease (0.6 +/- 6.62 ng/ml) compared with patients without significant coronary artery disease (-5.6 +/- 10.32 ng/ml) (mean +/- SD) (p less than 0.05). Further analysis revealed that patients with eccentric, irregular coronary artery lesions or intraluminal filling defects had a significantly elevated coronary sinus and aortic serotonin difference (3.1 +/- 5.54 ng/ml) compared with those with smooth concentric lesions (-1.9 +/- 6.61 ng/ml) (p less than 0.02). These data suggest that serotonin is released into the coronary circulation of some patients with coronary artery disease, especially those with frequent angina and complex coronary lesions. Although serotonin may be released in some patients with coronary artery disease, the specific pathophysiologic role of serotonin in the development or perpetuation of certain coronary syndromes in humans remains to be determined. PMID- 2910539 TI - Superoxide dismutase reduces reperfusion arrhythmias but fails to salvage regional function or myocardium at risk in conscious dogs. AB - To determine if oxygen free radical scavengers administered before coronary artery reperfusion can limit reperfusion arrhythmias, increase the return of regional function in ischemic myocardium, and reduce tissue necrosis at 1 week after 90-minute coronary artery occlusion and reperfusion, conscious dogs were treated with superoxide dismutase (SOD) and catalase before and for 1 hour after coronary artery reperfusion. Another group was treated with recombinant SOD (rSOD) because the commercially available SOD and catalase contained endotoxin. The conscious dogs were studied 3-4 weeks after implanting left ventricular pressure gauges, ultrasonic wall thickness gauges in the posterior left ventricular wall, left atrial catheters, and arterial catheters, Doppler flow transducers, and hydraulic occluders on the left circumflex coronary artery. The only beneficial effect observed was that the number of arrhythmic beats per minute in the rSOD-treated group was significantly lower (p less than 0.05) when compared with a control group after coronary artery reperfusion. Treatment neither increased the amount of recovery of wall thickening in the ischemic zone nor reduced infarct size when expressed either as a percentage of the area at risk or as a function of collateral blood flow in the ischemic zone. For example, infarct size as a percentage of the area at risk was 32.6 +/- 5.8%, 37.4 +/- 6.4%, 28.3 +/- 5.1% in the control, SOD and catalase-, and rSOD-treated groups, respectively. Thus, although treatment with oxygen free radical scavengers invoked a transient reduction in the number of reperfusion arrhythmias, this treatment in conscious dogs failed to improve regional myocardial dysfunction or reduce the amount of necrosis when compared with a control group. The lack of a sustained salutary effect may indicate that longer periods of treatment with free radical scavengers are required in chronic preparations. PMID- 2910540 TI - Local platelet activation causes vasoconstriction of large epicardial canine coronary arteries in vivo. Thromboxane A2 and serotonin are possible mediators. AB - The goal of the present study was to demonstrate that intracoronary platelet deposition may trigger intense vasoconstriction of large epicardial coronary arteries in vivo and that this is largely mediated by thromboxane A2 and serotonin released by activated platelets. Cyclic flow variations (progressive declines in blood flow followed by sudden restorations of flow) due to recurrent intracoronary platelet activation and thrombus formation were induced by damaging the endothelium and placing a cylindrical constrictor on the left anterior descending coronary artery (LAD) in open-chest, anesthetized dogs. Coronary diameters were measured in vivo by means of ultrasonic crystals sutured on the LAD immediately distal to the constrictor (LAD1) and 1 cm below (LAD2) and on the circumflex coronary artery (Cx). Coronary artery diastolic diameters were measured continuously before and during cyclic flow variations and after they were abolished by administration of LY53857, a serotonin-receptor antagonist (group 1, n = 7), or SQ29548, a thromboxane-receptor antagonist (group 2, n = 7). During cyclic flow variations, at the nadir of coronary flow, LAD1 (a site of maximal platelet accumulation) cross-sectional area decreased by 52 +/- 10% and 38 +/- 6% in group 1 and 2 animals, respectively (p less than 0.001 compared with values recorded during a brief LAD occlusion obtained by a suture snare), whereas LAD2 (a site of minimal or no platelet accumulation) cross-sectional area did not differ from that recorded during the brief LAD occlusion. SQ29548 abolished cyclic flow variations in seven of seven dogs and LY53857 in six of seven, but they affected the increased coronary vasoconstriction differently: LAD1 cross sectional area increased by 32 +/- 6% of the control value in SQ29548-treated animals, whereas it returned to baseline dimension values in the LY53857-treated group as these interventions also abolished the cyclic flow variations. We conclude that a marked coronary vasoconstriction may be triggered by local platelet deposition and that thromboxane A2 and serotonin are mediators of this vasoconstriction. PMID- 2910541 TI - Influence of contractile state on curvilinearity of in situ end-systolic pressure volume relations. AB - Although in situ end-systolic pressure-volume relations (ESPVRs) are approximately linear throughout a limited load range, they often yield seemingly "negative" volume axis intercepts (V0) and V0 shifts with inotropic interventions. We tested whether or not these findings could stem from in situ ESPVR nonlinearity, and we examined the physiologic meaning and limitations of linearized ESPVR variables frequently used for assessing contractile state. Continuous left ventricular pressures and volumes were obtained by micromanometer and conductance (volume) catheters in six open-chest dogs. Left ventricular loading was varied throughout a wide range by rapid left atrial hemorrhage into a reservoir. Propranolol and verapamil were administered to reduce inotropic state, with heart rate maintained by atrioventricular sequential pacing. ESPVRs were fit to nonlinear [Pes = a(Ves-V'0)2 + b(Ves-V'0)] and linear (Pes = Ees (Ves-V0)] models. Contractile state was assessed by the slope of the ESPVR at V'0 (b, of nonlinear model) and by two other ESPVR model-independent measures: the slope of the dP/dtmax and end-diastolic volume relation, and the slope of the stroke work and end-diastolic volume relation. ESPVR was frequently curvilinear, and a significant correlation existed between the extent of nonlinearity (a) and contractile state. Volume intercepts derived from linear fits to the high load ESPVR range were mostly negative and were dependent on changes in Ees. V0 estimates derived from the low load portion were positive and relatively insensitive to Ees. Thus, in situ ESPVR displays contractility-dependent curvilinearity. The contractility range throughout which ESPVRs are essentially linear is typical for isolated hearts, but the range represents low values for in situ ventricles. Despite curvilinearity, Ees determined in situ throughout limited load ranges can accurately assess inotropic state; however, comparisons between ESPVRs should consider potential nonlinearity, and if possible, they should be made within similar end-systolic pressure ranges. PMID- 2910542 TI - Nonuniformity of the transmural distribution of coronary blood flow during the cardiac cycle. In vivo documentation by contrast echocardiography. AB - This study was performed to examine the transmural (endocardial vs. epicardial) heterogeneity of myocardial blood flow during the cardiac cycle (systole vs. diastole). Twenty-four contrast echocardiographic injections were performed in seven open-chest anesthetized dogs either into left anterior descending or circumflex coronary artery or into the aortic root. Two-dimensional echocardiography in short-axis view was performed and was digitized off-line into a 256 x 256 pixel matrix with 256 gray levels/pixel. All end-diastolic and end systolic frames before and to peak contrast were analyzed. A region of interest corresponding to the most intensely opacified myocardial segment was traced, the mean videodensity measured, and the frame of initial contrast appearance detected. The region of interest was divided into three equal parallel layers corresponding to the endocardial, midcardial, and epicardial myocardium. When the echocardiographic contrast effect initially appeared in diastole, the increment in videodensity was greater for the endocardium (131 +/- 48%) than for the epicardium (71 +/- 37% of the increment in videodensity of the entire wall) (p less than 0.05). This inhomogeneity subsequently disappeared in the following end systolic frame. When the initial echocardiographic contrast effect appeared in systole, intensity was higher in epicardium (136 +/- 83%) than in endocardium (60 +/- 60%) (p less than 0.05). However, in the following diastole, intensity was not significantly different for the two layers. Thus, myocardial contrast echocardiography demonstrates that coronary blood flow is primarily subendocardial in distribution during diastole and subepicardial during systole. PMID- 2910543 TI - Mitral valve prolapse and regurgitation. PMID- 2910544 TI - Guidelines for ambulatory electrocardiography. A report of the American College of Cardiology/American Heart Association Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (Subcommittee on Ambulatory Electrocardiography). PMID- 2910545 TI - In vivo measurement of thromboxane B2 and 6-keto-prostaglandin F1 alpha in humans in response to a standardized vascular injury and the influence of aspirin. AB - The effects of smoking, aspirin ingestion, and sex differences on bleeding times and bleeding time thromboxane B2 and 6-keto-prostaglandin (PG)F1 alpha production were examined. Nonsmoking men produced more thromboxane B2 (3.99 +/- 0.76 ng/ml) than nonsmoking women (2.13 +/- 0.24 ng/ml). Female smokers produced more thromboxane B2 (5.01 +/- 0.97 ng/ml) than nonsmoking women. Twenty-four hours after a single dose of 600 mg aspirin, in vitro production of thromboxane B2 in response to collagen fell by 95%, whereas in vivo production of thromboxane B2 and 6-keto-PGF1 alpha in bleeding time blood fell by 87% and 66%, respectively. Subjects with the lowest absolute levels of thromboxane B2 24 hours after aspirin were also those with the longest postaspirin bleeding times. Recovery of 6-keto PGF1 alpha production was faster than recovery of thromboxane B2 production, but 6-keto-PGF1 alpha production for most subjects was still below basal 72 hours after aspirin. The influence of two different doses of long-term aspirin (80 mg every other day and 325 mg daily) on the in vivo production of thromboxane B2 and 6-keto-PGF1 alpha was studied in normals and diabetics. After 14 days of 80 mg aspirin every other day, thromboxane B2 and 6-keto-PGF1 alpha production were both substantially inhibited (93% and 78%, respectively). After 14 days of 325 mg aspirin daily, thromboxane B2 production was similarly substantially inhibited (93%), whereas 6-keto-PGF1 alpha was significantly less affected (only 45% inhibition). Study of a second group of five normal subjects confirmed that 6 keto-PGF1 alpha production was significantly inhibited 24 hours after the first dose of 325 mg aspirin but was not significantly less than basal after 14 days of 325 mg aspirin. The results suggest that 325 mg aspirin daily is more antithrombotic compared with 80 mg every other day due to the superior preservation of prostacyclin production. PMID- 2910546 TI - Predicting ventricular tachycardia cycle length after procainamide by assessing cycle length-dependent changes in paced QRS duration. AB - To determine if paced cycle length-dependent changes in the QRS duration correlate with the change in ventricular tachycardia (VT) cycle length after procainamide, we measured the QRS duration during sinus rhythm and during right ventricular pacing before and after procainamide (mean concentration, 9.9 micrograms/ml) in 18 patients with morphologically identical VT induced at both study periods. Pacing was performed at 600 msec or the longest cycle length that allowed for uninterrupted capture and at a cycle length that was within 50 msec of the VT cycle length observed during the control study (mean, 313 +/- 51 msec). After procainamide, the VT cycle length increased from 285 +/- 62 to 368 +/- 70 msec (percent change, 30 +/- 13%). The QRS duration during sinus rhythm increased from 125 +/- 25 to 145 +/- 29 msec (percent change, 16%). The QRS duration at both paced cycle lengths was the same in the baseline state (191 +/- 26 msec). However, the change in QRS duration after procainamide at the shorter paced cycle length compared to a 39 +/- 13 msec (18%) increase at the longer paced cycle, p less than 0.001. There was a significant correlation between the percent change in QRS duration at the shorter paced cycle length and the percent change in VT cycle length (r = 0.84, p less than 0.001) with the relation expressed by the regression equation: percent change in VT cycle length = -2.8 + 1.16 x percent change in QRS duration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2910547 TI - Importance of aortic baroreflex in regulation of sympathetic responses during hypotension. Evidence from direct sympathetic nerve recordings in humans. AB - Arterial baroreceptors in the carotid sinus and aortic arch regions reflexly regulate heart rate and peripheral vascular responses during changes in arterial pressure. The relative influence of these two arterial baroreflex pathways on the control of these autonomic responses is debatable. Recent studies in our laboratory demonstrate that the aortic baroreflex produces substantial and sustained inhibition of efferent sympathetic nerve activity to muscle (MSNA) during increases in arterial pressure. The regulation of MSNA by these two baroreflexes in humans during hypotension, and particularly the role of the aortic baroreflex, remains undefined. We therefore performed a new series of studies to assess the relative influence of the aortic and carotid baroreflexes on MSNA responses during sustained decreases in arterial pressure. In eight normal male subjects, aged 23 +/- 1 years (mean +/- SEM), we directly measured mean arterial pressure, heart rate, central venous pressure, and MSNA (microneurography) during hypotension (combined aortic and carotid baroreceptor deactivation) produced by intravenous infusion of sodium nitroprusside and during nitroprusside infusion with superimposed application of external neck suction. Neck suction was applied at levels sufficient to maintain transmural carotid sinus pressure above control levels (carotid baroreceptor activation) while the aortic baroreflexes remained deactivated. Central venous pressure was maintained constant with volume infusion. We also studied responses of these same subjects to direct carotid baroreceptor deactivation with the application of external neck pressure. During neck pressure alone, there was a reflex increase in mean arterial pressure; thus, during this portion of the protocol, we achieved carotid baroreceptor deactivation with some aortic baroreceptor activation. Nitroprusside infusion (combined aortic and carotid deactivation) decreased mean arterial pressure from 90.8 +/- 3.1 to 77.8 +/- 1.1 mm Hg (p less than 0.01) with concomitant increases in heart rate from 62.6 +/- 3.0 to 89.7 +/- 6.1 beats/min (p less than 0.001) and in MSNA from 273.8 +/- 43.0 to 950.6 +/- 133.5 units (p less than 0.001). During continued nitroprusside infusion with superimposed neck suction (aortic baroreceptor deactivation and carotid baroreceptor activation), mean arterial pressure decreased to 70.3 +/- 1.9 mm Hg (p less than 0.001 vs. control), heart rate decreased to 82.5 +/- 6.5 beats/min (p less than 0.01 vs. control or vs. nitroprusside alone), but MSNA remained markedly increased at 889.7 +/- 105.1 units (p less than 0.001 vs. control; p = NS vs. nitroprusside alone).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2910548 TI - Flow-mediated and reflex changes in large peripheral artery tone in humans. AB - Studies of peripheral blood vessels in humans have focused primarily on regulation of blood flow and vascular resistance, which are thought to reflect small vessel caliber. Recent studies in animals have identified flow-mediated and neurogenic changes in large artery diameter. This study tested for flow-mediated dilatation and reflex constriction of the brachial artery in humans. A dual crystal pulsed Doppler system was used to measure brachial artery diameter and blood flow proximal to the antecubital fossa. To test for flow-mediated dilatation, flow through the brachial artery was altered by an occluding cuff placed on the forearm distal to the site of brachial artery flow and diameter measurement. Control blood flow was 123 +/- 20 ml/min, and brachial artery diameter was 4.74 +/- 0.17 mm (mean +/- SEM). By inflating the distal occluding cuff (distal circulatory arrest), flow was reduced through the brachial artery to 21 +/- 5 ml/min (p less than 0.005), and brachial artery diameter was reduced to 4.35 +/- 0.20 mm (p less than 0.001). By deflating the distal occluding cuff after 10 minutes (reactive hyperemia), brachial artery flow was increased to 358 +/- 55 ml/min (p less than 0.001), and diameter was increased to 5.6 +/- 0.19 mm (p less than 0.001). These interventions did not change systemic arterial pressure and, as measured in three subjects, caused only small changes in local brachial artery distending pressure. Thus, both increased and decreased brachial artery blood flow produced significant changes in brachial artery diameter without altering arterial distending pressure. These data provide evidence for flow-mediated dilatation in humans.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2910549 TI - Four nonisotopic immunoassays of free thyroxin evaluated. AB - We evaluated four new nonisotopic immunoassays of free thyroxin (FT4)--Amerlite FT4 (Amersham International), Magic Lite FT4 (Ciba Corning Diagnostics), Stratus FT4 (Dade--Baxter Travenol), and FT4 Enzelsa (Compagnie ORIS Industrie)--by comparison with two FT4 radioimmunoassays: Amerlex and Sclavo. Inter- and intra assay coefficients of variation were less than 10% in the working range and there was no significant interaction between the tracer conjugate and albumin. All methods except Enzelsa gave results equivalent to those obtained with the Sclavo chromatographic technique. In a population consisting of 325 euthyroid subjects and 111 hyperthyroid and 61 hypothyroid patients without any treatment, we observed slight overlaps between the hyperthyroid and euthyroid populations and diagnostic sensitivities were approximately 0.95 and 0.80 for hyperthyroidism and hypothyroidism. In specific populations (69 patients with chronic renal failure, 20 patients in intensive-care, 17 patients treated with heparin, and 27 pregnant women), results were quantitatively similar to those obtained by the Sclavo assay. We conclude that these nonisotopic methods are a valid alternative to current radioisotopic commercial methods. PMID- 2910550 TI - Evaluation of a radioimmunoassay of urinary cortisol without extraction. AB - We evaluated the Kallestad "Quanticoat" cortisol RIA for direct (no extraction) measurement of urinary free cortisol, which requires no solvent extraction. An analytical-recovery study showed a linear regression of y (measured) = 0.65x (added) + 37.5 micrograms/L (Sy.x = 21.4 micrograms/L, r = 0.978, n = 48). Recovery appeared to vary with the urine used and with the concentrations of cortisol added. Within- and between-run CVs were less than or equal to 4.1% and less than or equal to 3.8%, respectively. Cross reactivities were low, except for prednisolone (20.5%). This no-extraction method gave higher values for urinary free cortisol than did either an RIA method involving extraction or an HPLC method. A comparison study with the HPLC (x) and with the method involving extraction (x') gave the following Deming-debiased regression equations: y = 1.60x + 68.8 (Sy.x = 34.4, n = 29) and y = 1.33x' + 0.69 (Sy.x = 40.3, n = 66), respectively. We conclude that the no-extraction method may give misleading results for patients' diagnosis or management if this cross reactivity is not taken into account. PMID- 2910551 TI - Improved determination of vanadium in biological fluids by electrothermal atomic absorption spectrometry. AB - We made sensitive and accurate electrothermal atomic absorption spectrometric measurements of vanadium in small volumes of serum. The wet-digested sample was extracted into an organic solvent, with N-benzoyl-N-(o-tolyl)hydroxylamine (BTA) as the chelating reagent. After evaporating the solvent, we dissolved the residue in acetic acid, and injected a 60-microL aliquot into a graphite furnace. In this way we could measure vanadium concentrations as low as 80 ng/L in 4 mL of serum. The within-run CV was 3.3% for serum, 7.7% for urine. Analytical recoveries of vanadium added to serum and urine were 90.3% and 90.8%, respectively. We measured vanadium concentrations in sera from 64 healthy persons (group 1), 15 nondialyzed uremic patients (group 2), and 11 hemodialyzed patients (group 3). The highest concentration of vanadium in group 1 was 240 ng/L; about 60% of the values for this group were less than 80 ng/L. In group 3, the vanadium concentrations were extremely high (15 +/- 14.2 micrograms/L, mean +/- SD), less so (but still above normal) in group 2 (1.58 +/- 3.16 micrograms/L). PMID- 2910552 TI - Clinical and analytical evaluation of different methods for measurement of creatine kinase isoenzyme MB. AB - We evaluated the clinical and analytical performance of the new immunochemiluminometric assay (ICMA; Ciba Corning) for measurement of creatine kinase isoenzyme MB (CK-MB), and compared it with three other methods: immunoradiometric assay (IRMA; International Immunoassay Labs); immunoinhibition assay (Seradyn); and an immunoinhibition/column method (Du Pont). Intra-test precision for all kits was good. We evaluated 32 patients' samples by all four methodologies. Only one of the four methods (aca, Du Pont) showed evidence of linearity. Efficiency in the diagnosis of myocardial injury in our study ranged from 53% (Seradyn) to 96% (Du Pont). We evaluated serial specimens from 20 separate patients by the IRMA and the ICMA to determine whether myocardial injury could be diagnosed earlier by the ICMA. In patients with acute myocardial infarction, the ICMA displayed positive values earlier and longer than the IRMA, suggesting that the ICMA is suited for screening for myocardial damage in hospitalized patients. PMID- 2910553 TI - Effects of various serum proteins on quantification of fructosamine. AB - We determined fructosamine concentrations with the CentrifiChem 600 centrifugal analyzer and the Hitachi 737 discrete analyzer. Reference intervals agreed with the most recently published results, and values in fasting patients were significantly correlated with glycated hemoglobin, plasma glucose, albumin, beta- and gamma-globulins, IgG, IgA, IgM, and total protein. Partial correlation analysis showed that only fructosamine and IgA were dependently related. In a group of nondiabetic patients with pathological values for IgA concentrations, 79.4% had pathological values for fructosamine. These results throw doubt on the clinical value of fructosamine determinations if serum IgA is not taken into account. PMID- 2910554 TI - Improved method for calculating calcium fractions in plasma: reference values and effect of menopause. AB - Multiple linear regression analysis showed that total calcium was significantly and positively related to albumin, globulin, anion gap, and bicarbonate in plasma from 556 normal postmenopausal women. The residual constant of 1.21 mmol/L approximated the normal mean for ionized calcium in plasma. The coefficients derived from the multiple regression analysis were used to calculate ionized calcium from total calcium and ligand concentrations in a series of 105 clinical cases in whom ionized calcium was measured with the calcium electrode. The regression equation was y = 1.00x -0.0039 mmol/L, where x is measured and y calculated Ca2+ (r = 0.78, P less than 0.001). The protein-bound, ultrafiltrable, and complexed fractions of the calcium were also calculated for plasma from 69 normal young men, 66 normal young women, and 305 normal postmenopausal women. The increased plasma calcium in the postmenopausal group was accounted for by an increase in the complexed fraction, due to increases in plasma bicarbonate and anion gap. PMID- 2910555 TI - Turbidimetric latex immunoassay of placental lactogen on microtiter plates. AB - In this latex immunoassay for human placental lactogen, microtiter plates are used as the reaction vessel and the absorbance at 405 nm is measured to quantify the reactions. This 30-min assay necessitates only one serum dilution and two pipetting steps. The calibration curve extends from 0.5 to 15 mg/L. CVs range from 4.2% to 7.0% for within-run determination and from 7.0% to 11.2% for between run determinations. A correlation coefficient of 0.949 was obtained for 84 sera when the method was compared with a commercial radioimmunoassay. PMID- 2910556 TI - Effect of ether or ketamine anesthesia on rat uterine estrogen and progesterone receptors. AB - Rat uterine estrogen receptors (ER) and progesterone receptors (PR) have been used as controls in ER and PR assays of breast tumors. Stunning or decapitation of experimental animals without prior anesthesia is no longer acceptable as a method of killing. Thus, we compared the effects of two anesthetics on the concentration of rat uterine ER and PR. Rats were killed by one of three methods: (a) stunning, (b) ether anesthesia followed by decapitation, or (c) ketamine anesthesia followed by decapitation. ER and PR concentrations were determined by titration assay, with dextran-coated charcoal separation, and quantified by Scatchard analysis. No significant differences were found in mean receptor concentrations or dissociation constants for the three groups. The results indicate that there is no residual effect of diethyl ether or ketamine hydrochloride on the binding of either estrogen or progestin to their respective receptors. The use of decapitation after either ether or ketamine anesthesia is appropriate for measuring ER and PR receptors in rat uteri. PMID- 2910557 TI - Differences between values for plasma and serum in tests performed in the Ektachem 700 XR Analyzer, and evaluation of "plasma separator tubes (PST)". AB - We measured 25 analytes in plasma and serum from the same blood specimen, using the Kodak Ektachem 700 XR Analyzer. For 22 of the analytes, values for plasma were practically the same as those for serum; for the other three, differences between concentrations in plasma and serum were significant, both statistically and medically. Values for the same analytes in plasma from regular heparinized tubes were essentially indistinguishable from those for plasma obtained by use of Plasma Separator Tubes (PST). PMID- 2910558 TI - Evaluation of the IFCC reference method for alanine aminotransferase: spurious blank ALT activity due to contamination of D-alanine with L-alanine, and recommendations for a correction. AB - During an evaluation of the IFCC reference method for alanine aminotransferase (ALT, EC 2.6.1.2), we noted that the specimen blank activity reaction was markedly increased. Experience with five different lots of D-alanine from four commercial sources indicated that substantial and varying negative bias (up to 10%) could be introduced into the blank-corrected ALT activity, depending on the lot of D-alanine used. Although the IFCC procedure for ALT mentions the possibility of this L-alanine contamination, we believe that the degree of contamination in commercial reagents is underestimated. Analyzing the five lots of D-alanine for L-alanine, we found the magnitude of negative bias to be correlated directly with L-alanine contamination. Here, we describe a quick, sensitive assay based on coupled reactions of L-amino acid oxidase/peroxidase for quantifying L-alanine in the concentration range of 0-15 mmol/L without a sample dilution step. Results by this alternative L-alanine assay agreed well with those recommended in the IFCC ALT procedure. Further examination suggested an even simpler solution to the L-alanine contamination problem, because we found no difference in the blank-corrected ALT activity determined in Tris HCl buffer, with or without D-alanine (free of L-alanine). We therefore propose that D alanine be omitted from the IFCC reference ALT procedure. PMID- 2910559 TI - Fibronectin is unsuitable as a tumor marker in pleural effusions. AB - We studied 75 patients with nonmalignant pleural effusions (50 with pneumopathy, 16 with pulmonary tuberculosis, and nine with congestive heart failure) and 33 patients with malignant pleural effusions. We selected 105 mg/L as the most suitable cutoff concentration of fibronectin for distinguishing between the two groups. We found high concentrations of fibronectin in 21 of the 33 patients with malignant pleural fluid but also in 37 of the 75 patients with nonmalignant pleural fluid. Evidently, measuring fibronectin in pleural fluid will not help in differentiating nonmalignant from malignant pleural fluids (diagnostic accuracy: 55%). PMID- 2910560 TI - Salivary progesterone excellently reflects free and total progesterone in plasma during pregnancy. AB - To see if saliva is a valid substitute for plasma in assay of progesterone even when concentrations of hormone and binding proteins are fluctuating, we determined the concentrations of total and free progesterone in plasma and salivary progesterone in specimens from 36 women volunteers during the course of pregnancy and six weeks postpartum, using a highly specific RIA for total progesterone after extraction and chromatographic purification of the steroid. The free fraction in plasma was determined via equilibrium dialysis, followed by the same RIA analysis for progesterone in the dialysate. Despite the dramatic increases in concentrations of total progesterone and binding proteins in plasma during pregnancy, we found highly significant correlations between total and free progesterone in plasma and salivary progesterone in the group as a whole as well as individuals (P less than 0.001 in almost all cases). The proportion of free progesterone in plasma and of salivary progesterone relative to total progesterone in plasma remained constant at approximately 1% and 0.5%, respectively, whereas during the postpartum period there was much more variance. Evidently salivary progesterone is a very good alternative to plasma as a sample for use in follow-up during pregnancy. PMID- 2910561 TI - One-step protocol for assays of total and direct bilirubin with stable combined reagents. AB - We describe an improved colorimetric method for assays of total and direct bilirubin in serum. Bilirubin reacts with diazotized sulfanilic acid in an acidic medium to form a blue azopigment. Total bilirubin is assayed in the presence of reaction accelerators (caffeine, urea, and citric acid), direct bilirubin in their absence. The azo compound so formed is read at the same wavelength (570 nm) in both assays. A sample blank is run in parallel. Standard curves are linear for total and direct bilirubin concentrations up to 513.0 and 256.5 mumol/L, respectively. The method is characterized by (a) use of the same protocol for both assays, i.e., a one-step procedure with short reaction time (5 min at room temperature), and (b) use of a single working solution, which, refrigerated, is stable for one month. The method is reliable, yields results that compare closely with those of the classical Jendrassik--Grof method, is suitable for routine use, and lends itself to automation. PMID- 2910562 TI - A labile enzyme in fresh human serum interferes with the assay of carboxypeptidase N. PMID- 2910563 TI - Serum glycated beta-lipoprotein determined by agarose-gel electrophoresis with nitroblue tetrazolium coloration. PMID- 2910564 TI - A new pitfall in plasma amino acid analysis. PMID- 2910565 TI - Immunoturbidimetry of prealbumin (transthyretin) in a microcentrifugal analyzer. PMID- 2910566 TI - Sugar-chain analysis of alkaline phosphatase by lectin affinity chromatography in serum from a patient with osteosarcoma. PMID- 2910567 TI - Reference intervals for two bone-derived enzyme activities in serum: bone isoenzyme of alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TR-ACP). PMID- 2910568 TI - Calibration of 125I immunoassay measuring cyclosporin A. PMID- 2910569 TI - Effect on results of temperature at which Reflotron strips are stored. PMID- 2910570 TI - Bence Jones immunoglobulins in the urine of patients with multiple sclerosis. PMID- 2910571 TI - Units for peptide hormones. PMID- 2910572 TI - Precision of measurement of glycated hemoglobin by affinity chromatography on regenerated columns. PMID- 2910573 TI - Fructosamine: matrix problems with standards based on protein matrices. PMID- 2910574 TI - Total digoxin-like immunoreactive factor(s), total bilirubin concentration, and birth weight in neonates. PMID- 2910575 TI - Errors in a report: thyroid dysfunction detection strategy. PMID- 2910576 TI - Effect of citrate on the urinary excretion of calcium and oxalate: relevance to calcium oxalate nephrolithiasis. AB - Studies in 24 recurrent oxalate stone-formers have shown that values for urinary calcium excretion for this group on at-home diets vary significantly (P less than 0.001) more than values for creatinine excretions. By placing stone-formers on controlled in-hospital diets and measuring their calcium excretions, we were able to predict probable outpatient hypercalciuria (greater than 7.5 mmol/day) with a sensitivity of 95% and a specificity of 95%. In this study, the renal loss of calcium during low-calcium diets was proportional to the absorptive hypercalciuria during high-calcium diets. Calcium loading experiments in fasted stone-formers and normal subjects indicated that citrate, at citrate:calcium molar ratios ranging from 0.12 to 1, stimulated urinary calcium excretion more than did calcium carbonate loading alone. In addition, citrate also significantly (P less than 0.05) increased the excretion of urinary oxalate by two normal subjects for a given load of calcium oxalate. Malabsorption of citrate and possibly other hydroxycarboxylic acids may thus predispose to oxalate nephrolithiasis by promoting calcium and oxalate absorption. PMID- 2910577 TI - Alkaline phosphatase isoenzymes of liver and bone origin are incompletely resolved by wheat-germ-lectin affinity chromatography. AB - We used wheat-germ-lectin affinity chromatography as a tool to investigate the structure of alkaline phosphatase (ALP, EC 3.1.3.1) and to obtain fractions enriched in either bone or liver ALP activity. Liver and bone isoenzymes in serum samples were incompletely resolved except that the activity in the nonretained fraction (fraction 1) always represented pure liver isoenzyme and constituted a larger percentage of total activity in pooled sera with increased liver ALP activity than in pooled sera with increased bone activity. In contrast, a more avidly retained ALP activity, presumably with high glycosylation, was found in human serum with high activity of bone ALP. Using a solid-phase immunoassay, we examined the fractions obtained from the wheat-germ-lectin-Sepharose 4B column to determine whether the isoenzyme preference of the monoclonal antibody was markedly influenced by the degree of glycosylation. Whether samples contained high proportions of liver or of bone isoenzyme activity, the nonretained fraction contained a higher percentage of liver ALP, whereas the more strongly bound fraction contained a higher percentage of bone ALP. Except for eluted fractions that either contained no detectable N-acetylglucosamine or the highest percentage of it, the avidity of the liver-isoenzyme-specific monoclonal antibody for ALP seemed to be independent of the degree of glycosylation, suggesting that the epitope for monoclonal antibody may be expressed in some structure other than the carbohydrate moieties. PMID- 2910578 TI - Liquid-chromatographic determination of acetylated hemoglobin. AB - In this liquid-chromatographic assay for acetylated hemoglobin in human blood, glycated hemoglobins in hemolysates are first removed by affinity chromatography on boronate-agarose columns. Acetylated hemoglobin in the nonretained fraction is determined by cation-exchange chromatography. The absorbance of the effluent is monitored at 415 nm. The mean within-assay CV was 8.5%, the between-assay CV 17%. The mean proportion of acetylated hemoglobin in 20 pregnant, nondiabetic women was 1.9%, and in 17 alcoholics it was 2.7%. Rapid and reproducible, this method is suitable for use in routine determination of acetylated hemoglobin. PMID- 2910579 TI - An improved radioimmunoassay of C-peptide and its application in a multiyear study. AB - A commercial radioimmunoassay (RIA) for human proinsulin C-peptide was modified to improve its ruggedness and specificity, to decrease the influence of specimen matrix, and to shorten "hands-on" time. In the new protocol, we prepare calibrators in a C-peptide-free serum pool, prepared by treatment with activated charcoal (biological matrix), instead of in a defined matrix. This yielded essentially 100% analytical recoveries for C-peptide concentrations up to 300 pmol/L, a broader analytical range. We also corrected calibrators and unknown samples for nonspecific binding (NSB). Decreasing the concentration of ethanol (from 950 to 880 mL/L) for differential precipitation of the antigen-antibody complex resulted in an NSB of less than 10%, while maintaining high bound/total count percentages for samples and calibrators. C-peptide is thermally unstable without aprotinin at -20 degrees C and with or without aprotinin at 4 degrees C or above, but multiple freeze-thaw cycles do not affect C-peptide in serum. The modified C-peptide assay was applied to plasma from a multiyear study (fasting and post-carbohydrate-challenge subjects). During the four years of the study CVs ranged from 1.9% to 8.6% for replicate analyses of C-peptide in samples with concentrations less than or equal to 500 pmol/L. Between-run CVs were 3.8% to 8.2%, total CVs 3.8% to 10.7%. PMID- 2910580 TI - High-performance liquid-chromatographic analysis for serotonin and tryptamine excreted in urine after oral loading with L-tryptophan. AB - We describe a method used for determining serotonin and tryptamine in urine after oral loading with their precursor amino acid. Several factors affecting prepurification and chromatographic separation of both indoleamines were optimized, including sample extraction and mobile-phase composition. Under optimal conditions, serotonin and tryptamine are extracted from urine samples together with an internal standard, and then they are separated by reversed-phase chromatography followed by native fluorescence detection. The analytical procedure is simple enough to apply to routine analysis and performable at low cost. Sensitivity and selectivity of the method are satisfactory enough to determine urinary serotonin and tryptamine. By pursuing urinary excretion of serotonin and tryptamine after oral loading with L-tryptophan (30 mg per kilogram body weight), our method proves that urinary excretion of both indoleamines increases immediately after loading and reaches a maximum in about 45 min. PMID- 2910581 TI - Increased concentrations of heparin cofactor II in diabetic patients, and possible effects on thrombin inhibition assay of antithrombin III. AB - We compared concentrations of antithrombin III (AT-III) in plasma, as determined by an immunological method and by a functional thrombin inhibition method, in the presence of heparin in 160 blood samples from Type I diabetics. Although the correlation was highly significant (P less than 0.001) between the results obtained by the two methods, our data demonstrated that results by the thrombin inhibition assay, 121 (SD 15)%, expressed as percentages of the results for a normal plasma pool, were significantly (P less than 0.001) higher than by the immunoreactive method, 104 (SD 15)%, indicating an overestimation of functionally active AT-III. Concentrations of functionally active AT-III determined by a factor Xa inhibition assay, 105 (SD 13)%, were in the same range as immunoreactive AT-III. Addition of IgG antiserum to normal pooled plasma quenched only about 90% of the AT-III activity determined by the thrombin inhibition assay, but all of the AT-III activity determined by a factor Xa inhibition assay. These results demonstrate that the factor Xa inhibition assay is more specific for the determination of AT-III than the thrombin inhibition assay. We suggest that the high concentrations of heparin cofactor II, 117 (SD 17)%, might have caused an overestimation of AT III in this group of patients with diabetes Type I, and should not be overlooked in other clinical situations. PMID- 2910582 TI - Adenosine and dopamine simultaneously determined in urine by reversed-phase HPLC, with on-line measurement of ultraviolet absorbance and electrochemical detection. AB - This assay method allows the simultaneous determination of adenosine and dopamine in 0.5 mL of human urine within approximately 35 min, by using isocratic, reversed-phase, high-performance liquid chromatography coupled with an on-line detector for ultraviolet absorbance and electrochemical activity. The analytes were rapidly separated on an affinity column packed with phenylboronate-bonded silica. Mean recoveries for adenosine, 2-chloroadenosine (internal standard), dopamine, and (+/-)-isoproterenol (also an internal standard) were 91%, 99%, 88%, and 104%, respectively. The calibration curves for adenosine and dopamine were linear (r = 0.999, P less than 0.01) over the respective concentration ranges of 0.10 to 2.00 mg/L and 0.05 to 1.00 mg/L. Analytical precisions, assessed by the within-day and the day-to-day CVs, were 4.5% and 6.5% for adenosine, and 5.1% and 6.6% for dopamine, respectively. The mean (+/- SD) concentrations of adenosine (1.27 +/- 0.73 mg/L) and dopamine concentrations (0.38 +/- 0.25 mg/L) measured in urine from 19 healthy subjects agreed well with those previously reported. PMID- 2910583 TI - Preparation of fecal samples for assay of volatile fatty acids by gas-liquid chromatography and high-performance liquid chromatography. AB - We describe a procedure for preparing fecal samples for determination of volatile fatty acids (VFAs) by gas-liquid chromatography (GLC) and "high-performance" liquid chromatography (HPLC). The simple, one-step procedure involves only ultrafiltration through a membrane with a molecular-mass cutoff of 3000 Da. As revealed by the GLC chromatograms, ultrafiltration appears to be as effective as steam distillation in sample clean-up. It also enables higher, more reproducible analytical recoveries of long-chain VFAs. The VFA content of the filtrate can also be measured by HPLC. Use of the ion-exclusion mechanism completely resolves isobutyric acid and butyric acid on a cation-exchange column. The mean (+/- SD) percentage distribution values of VFAs (measured by GLC) from five healthy subjects were 56.0 +/- 3.5 (acetic acid), 17.0 +/- 5.3 (propionic acid), 2.9 +/- 1.5 (isobutyric acid), 18.8 +/- 5.8 (butyric acid), 2.3 +/- 1.2 (isovaleric acid), and 2.9 +/- 0.8 (valeric acid). PMID- 2910584 TI - Automated determination of cholinesterase activity in plasma and erythrocytes by flow-injection analysis, and application to identify subjects sensitive to succinylcholine. AB - This automated spectrophotometric method for determination of cholinesterase activity in erythrocytes and plasma is based on measurement of the choline produced at 30 degrees C by the hydrolysis of acetyl-, butyryl-, or succinylcholine. Blanks, standards, and samples are prepared by a Gilson robotic unit. Use of flow-injection analysis for detection allows use of smaller volumes of reagent and sample. We applied this method to the study of 91 healthy subjects and members of two families with succinylcholine sensitivity. Results with use of the three different substrates for determination of activity in plasma correlated well (r greater than 0.94). Results for plasma and erythrocytes from healthy subjects are lower in women less than 50 years old than in women greater than 50 years or men. Values for plasma obtained with succinylcholine substrate (range: 31 to 100 U/L) allow detection of very sensitive subjects--AA phenotypes (less than 10 U/L)--but do not distinguish the UA from the UU phenotype. PMID- 2910585 TI - An immunoassay of human band 5 ("tartrate-resistant") acid phosphatase that involves the use of anti-porcine uteroferrin antibodies. AB - We describe an immunoassay for human band-5 acid phosphatase in which antibodies to porcine uteroferrin, immobilized on Sepharose particles, are used. Band-5 acid phosphatase is the tartrate-resistant isoenzyme normally expressed in tissue macrophages such as osteoclasts and alveolar macrophages. The immunoassay is similar in reproducibility and sensitivity to assays based on inhibition by d tartrate. However, compared with the latter, the greater specificity of the immunoassay makes it markedly less susceptible to errors arising from the presence of non-band-5 acid phosphatases, e.g., from prostate. PMID- 2910586 TI - Thermal inactivation of L-thyroxin. AB - We assessed the extent of inactivation of L-thyroxin induced by exposure to heat in the presence of two vehicles. Preparations of L-thyroxin in the dry powder form, or dispersed in the solvents propylene glycol (water-like) or ethoxylated castor oil (oil-like), were heated at temperatures ranging from 65 to 160 degrees C, for 5- to 15-min periods. Heating L-thyroxin to a temperature below that of cooked bovine ground meat (72 degrees C) produced less than 10% degradation. Thermal degradation was pronounced only above 90 degrees C, and was almost completed at 160 degrees C. L-Triiodothyronine was the only thermal degradation product identified after L-thyroxin was heated at 125 degrees C. In a separate experiment we measured the melting point of L-thyroxin, 148.81 degrees C. This value agrees closely with the observed thermal sensitivity. We conclude that L thyroxin is not significantly degraded under conditions encountered during cooking of ground bovine meat for short times at moderate temperatures. PMID- 2910587 TI - Effects of retinoids on human thymus-dependent and thymus-independent mitogenesis. AB - The effects of all-trans-retinoic acid (RA), 13-cis-retinoic acid, and N-(4 hydroxyphenyl)retinamide on the mitogenic responses of various populations of human lymphocytes have been evaluated. Superoptimal concentrations of mitogens allowed the greatest RA-induced potentiation of lymphocyte proliferation. All three retinoids at concentrations as low as 5 x 10(-14)M significantly potentiated the proliferation of adenoidal and tonsillar lymphocytes stimulated by pokeweed mitogen (PWM). However, the responses of adenoidal and tonsillar lymphocytes to Staphylococcus aureus Cowan strain A were not potentiated by retinoids. Retinoids also caused significant potentiation of proliferation of PWM stimulated peripheral blood lymphocytes (PBL). However, endpoint concentrations of retinoids required to significantly potentiate PBL proliferative responses to PWM were much higher than required for potentiation of adenoidal or tonsillar lymphocytes. PBL responses to concanavalin A (Con A) were significantly potentiated by retinoid concentrations as low as 10(-8) to 10(-10) M. Retinoid potentiated responses were also observed wi Con A-stimulated thymocytes, but the endpoint concentrations required for significant potentiation were 10-fold higher than required to potentiate PBL responses to Con A. These data indicate that the sensitivity of lymphocytes to the retinoid-mediated potentiation of mitogenesis depends on the lymphoid compartment from which the cells are obtained. Tonsillar and adenoidal lymphocytes were the most responsive of the lymphocytes tested to the retinoid-induced potentiation of PWM responses. In addition, retinoids appear to selectively potentiate T cell-dependent proliferative activity. PMID- 2910588 TI - International Symposium on Immunoregulation in Clinical Diseases. Florence, Italy, May 26-27, 1988. Part 2. Proceedings. PMID- 2910589 TI - Pathways of kinin formation and role in allergic diseases. AB - We have developed new assays for the assessment of the plasma kinin forming system which have increased sensitivity and specificity. We utilize double antibody ELISA assays for quantitation of complexes of activated Hageman factor C1 inhibitor, kallikrein-C1 inhibitor, and kallikrein-alpha 2-macroglobulin which reflect activation of each enzyme. The fraction of cleaved high-molecular-weight kininogen is determined by immunoblotting using a monoclonal antibody to the light chain, and bradykinin is determined by radioimmunoassay. Activation of the Hageman factor-dependent pathway of kinin formation can occur when plasma is in contact with initiating surfaces or when C1 inhibitor function is diminished. The latter mechanism can occur in hereditary angioedema, in which the protein is absent or dysfunctional, or when plasma is diluted so that the effect of inhibitors is diminished and Hageman factor autoactivation is facilitated. Thus apparent "spontaneous" generation of bradykinin is seen upon incubation of plasma of hereditary angioedema patients under conditions in which normal plasma is unaffected. Studies of late-phase reactions have used a cutaneous model in which induced blisters are unroofed and challenged with antigen or buffer control using chambers which can be changed hourly. A time course of mediator release is obtained by assay of the blister fluids. Whereas most histamine is released during the first half hour, significantly elevated levels of activated Hageman factor and kallikrein complexes with C1 inactivator are seen in antigen challenged sites between 4 and 6 hr. The presence of such complexes correlated with the presence of late-phase reactions rather than the histamine values or the magnitude of the immediate reaction. Although late-phase reactions are characterized by cellular infiltration, release of a variety of inflammatory low molecular-weight mediators, and deposition of fibrin, activation of the Hageman factor-dependent pathway of kinin formation is also likely to be contributory. PMID- 2910590 TI - Nursing and technology: moving into the 21st Century. PMID- 2910591 TI - Glenohumeral movements of the involuntary inferior and multidirectional instability. AB - The glenohumeral movements of the involuntary inferior and multidirectional instability were studied by means of cineradiography. Using the devised two parameters, i.e., the shoulder center edge and glenoid angles, the author compared the glenohumeral movements of the normal shoulder with the involuntary inferior and multidirectional instability of the shoulder. The glenohumeral movements of the involuntary inferior and multidirectional instability showed not only an excessive excursion and sliding motion but also a deterioration of the scapular abduction and external rotation, with the arm progressively abducted. These phenomena were especially remarkable at the maximum elevation of the arm. The roentgenogram of the overhead view of the shoulder joint indicates whether or not there is an involuntary inferior and multidirectional instability, and whether or not these parameters can be useful for diagnosis of shoulder lesions. PMID- 2910592 TI - Position of shoulder arthrodesis measured with Moire photography. AB - A new method for measuring the position of a shoulder arthrodesis is presented. With Moire photography and two mirrors, it is possible to find the neutral position of the scapula and to record the position of the humerus with great accuracy. PMID- 2910593 TI - Subtrochanteric fractures of the femur. Results of treatment with the 95 degrees condylar blade-plate. AB - The results were retrospectively analyzed of 47 subtrochanteric fractures of the femur treated with a 95 degrees condylar blade-plate to establish whether two different surgical techniques yielded different results. Before 1981, treatment consisted of extensive visualization of the fracture lines, permitting anatomic reduction of all fragments, stable internal fixation with the blade-plate, and optional autologous bone grafting as recommended by the AO group. Twenty-four fractures were treated accordingly and constituted Group I of this study. In 1981, visualization of the fracture lines was abandoned, especially at the medial cortex; an indirect reduction technique was used to gain optimal alignment and stability without aiming at anatomic reduction, and bone grafting was discontinued. Twenty-three patients were treated accordingly and constituted Group II. The use of prophylactic antibiotics as a routine for all major trauma was instituted at the time the surgical technique was changed. Thus, only two of the 24 patients in Group I received antibiotics as opposed to 20 of the 23 patients in Group II. Average time to bony union for those fractures that healed primarily was 5.4 months in Group I and 4.2 months in Group II. Delayed or nonunion was 16.6% in Group I and 0% in Group II, and the infection rate was 20.8% versus 0% in the two groups. The four cases with a delayed union were aseptic, but three of the four nonunions were infected. The functional end result was comparable for both groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2910594 TI - Epidemiology of hip fractures in Siena, Italy, 1975-1985. AB - A survey of 1567 fractures of the proximal end of the femur due to minor trauma occurring in elderly people was performed. The fracture incidence rate per 100,000 individuals in the population at risk was calculated. Hip fracture prevailed in women with a sex ratio of women to men of 3.81; in both sexes the incidence was more closely related to age than any other factor. The incidence rate of fracture increased significantly in women during the period from 1975 to 1985, whereas there was no significant increase in men during this time. This change may be related to the continuing trend toward a greater proportion of elderly women in the population. The incidence rate in men showed a long-cycle periodic behavior correlated with the long-cycle trend of cloud cover and rainfall; it is possible that precipitation and a greater occurrence of femoral fractures might be interrelated in men. This parallelism was not evident in women. In women the rise in fracture rate was not continuous but decreased periodically. The zeniths of fracture incidence were preceded two years by a decrease in temperature and an increase in cloud cover and rainfall, suggesting a possible relationship between fractures and the diminution of ultraviolet radiation. PMID- 2910595 TI - Lateral facet syndrome of the patella. Lateral restraint analysis and use of lateral resection. AB - Thirty-eight knees in 34 patients with an average age of 22 years were diagnosed as having lateral facet syndrome (LFS), a painful compressive arthropathy of the lateral facet of the patella. This diagnosis was based on the physical findings of tenderness at the lateral patellofemoral joint line, tenderness over the vastus lateralis obliquus (VLO) tendon just above the patella, a positive medial apprehension test, and marked resistance to medial patellar displacement with the knee flexed 30 degrees. The most common complaints were patellar pain with activity, pain with prolonged knee flexion, intermittent knee swelling, and giving way. At surgery, the VLO, the lateral retinaculum (LR), and the anterior fibers of the iliotibial tract (ITT) were sequentially divided from the lateral border of the patella. Each was temporarily reattached to a cuff of soft tissue left on the patella using surgical clamps to determine its contribution to lateral restraint. The VLO was found to be the primary restraint in one-half of the knees. In one-third of the knees, all three of the structures contributed equally. In six knees, the primary restraint was the anterior fibers of the ITT, whereas the LR was the primary restraint in only two. The distal ends of these three structures were then resected to prevent rescarring and retethering. At a minimum follow-up period of two years, 87% had satisfactory relief of their patellar pain, had returned to normal activities, and had no or minimal physical findings of LFS. The procedure is recommended for patients who have failed other procedures and in those whose symptoms cannot be controlled by activity modification, exercises, bracing, or medication. PMID- 2910596 TI - Revision of septic total knee arthroplasty. AB - Nine patients with septic total knee arthroplasties (TKA) were treated between 1980 and 1984; six were gram-positive infections and three were gram-negative. Initial treatment included the maintenance of all solidly fixed components. Patients with loose components were treated with removal of all prosthetic material and subsequent reimplantation after a six-week course of antibiotics. At follow-up examination six of nine patients had satisfactory results. One patient maintained his original femoral and tibial components and one patient required a knee fusion to treat his recurrent gram-negative infection. Overall, complications were associated with chronic infection, gram-negative infection, and abnormalities of the extensor mechanism. PMID- 2910597 TI - Total condylar knee arthroplasty in osteoarthritis. A four- to six-year follow-up evaluation of 103 cases. AB - One hundred and three consecutive total condylar knee prostheses in patients with gonarthrosis inserted from 1979 to 1981 have been prospectively followed for four to six years. According to the New York Hospital for Special Surgery Knee Rating Scale, 58 knees (56%) were rated excellent; 34 (33%), good; seven (7%), fair; and four (4%), poor at the latest follow-up evaluation. The median preoperative score was 57 points and the median postoperative score 87 points. Thirteen knees (13%) had a radiolucency with a width of 2 mm or more beneath one or more of three tibial zones. In only one case did this represent a clinical loosening. Six knees (6%) had complications requiring reoperation. One deep infection was treated with an arthrodesis, one patellar button was revised after a traumatic patellar fracture, and three superficial skin necroses were surgically managed. Moreover, in one mechanically loosened tibial component, a revision has been planned. No complications were fatal. The modified total condylar I prosthesis is an excellent prosthetic design with a low failure rate in gonarthrosis. PMID- 2910598 TI - Early changes in gait and maximum knee torque following knee arthroplasty. AB - Fourteen knees in 11 individuals were studied before knee arthroplasty and at three and six months following surgery. Eleven of these knees were further evaluated at 12 months following surgery. At each evaluation, kinematic, electromyographic, and force plate data were gathered during level walking. Maximum knee extension and flexion torques were also determined. The greatest improvement in gait was noted in the first three postoperative months when velocity increased 13% and stride length increased 14%. After six months gait changes were negligible. Maximum knee torques in the osteoarthritic population were decreased at three months, then returned to preoperative levels at six months. In the rheumatoid population, maximum knee torques steadily increased up to six months following surgery. Gait abnormalities that persist at six months and beyond following knee arthroplasty appear to be most related to the presence of arthritis in joints other than in the operated knee(s). PMID- 2910599 TI - An experimental study of the redistribution of patellofemoral pressures by the anterior displacement of the anterior tuberosity of the tibia. AB - Using a series of miniature piezoelectric transducers constructed by the authors, a study was made of the effect of anterior displacement of the tuberosity of the tibia on the distribution of pressures in the patellofemoral joint. Proportionally, the most efficient displacements are those set at 1 cm; after this, and as advancement of the tuberosity is increased, the overall pressure continues to decrease progressively (although more slowly) because there are zones that, according to their situation, receive increased instead of decreased pressures. Consequently, values even higher than those of the original situation are reached. This is the case of the proximal part of the patella, particularly on its lateral facet. This situation can affect the results in cases where the lesion is preferentially located on the proximal part. In these cases it may be enough to advance 1 cm with which overall decompressions close to 50% of the pressure that initially affected the patellofemoral joint are obtained. In very evolved cases or when the lesions are located centrally or distally, it may be worthwhile to advance maximally in spite of the possible complications, seeking the greatest decompression effect that intense advancements can achieve. PMID- 2910600 TI - Subtalar dislocations. AB - Subtalar dislocations are uncommon injuries. In an effort to obtain accurate information, eight recent major series (more than five patients) were summarized, including the experience at the authors' institution between 1975 and 1985 (12 patients). Medial dislocations predominated (79.5%), lateral injuries accounted for 17% of cases, and posterior (2.5%) and anterior (1%) dislocations were infrequent. Associated fractures with medial (55%) and lateral (72%) dislocations were common. Open injuries with lateral dislocations (25%) were more common, and avascular necrosis was uncommon (4%-5%). Males predominated (81%). It was evident that symptomatic subtalar instability occurred in younger patients treated with shorter periods of immobilization. PMID- 2910601 TI - Ankle fractures treated using biodegradable internal fixation. AB - In order to reduce the resources needed for the removal of metallic fixation devices in fracture treatment, absorbable implants of biodegradable synthetic polymers were developed using self-reinforced lactide-glycolide copolymer and polyglycolide. In a prospective study 102 patients with displaced unimalleolar or bimalleolar fractures of the ankle were managed using internal fixation devices consisting of cylindrical biodegradable implants 3.2 or 4.5 mm in diameter and 50 or 70 mm in length. After open reduction of the fracture a channel was drilled from the tip of the malleolus into the cancellous bone through the fracture surfaces. A biodegradable rod of the same diameter was then tapped into the drill channel to fix the fracture. Postoperatively, the ankle was immobilized by a plaster cast for six weeks. An anatomic initial reduction was achieved in 93 patients (91%). A slight secondary displacement occurred in four patients. In six patients a sinus formation yielding remnants of the degrading implant was seen two to four months after the operation. This minor complication did not influence the union of the fracture or functional recovery. At the one-year follow-up examination there was no change in the ability to participate in sports and other physical activities in 89 patients (87%). The biodegradable fixation method is now the routine approach of the department in treating displaced unimalleolar and bimalleolar ankle fractures. New clinical applications for the implants are under trial. PMID- 2910602 TI - Reconstruction of neglected Achilles tendon rupture with Marlex mesh. AB - Reconstruction of the neglected Achilles tendon rupture was performed with marlex mesh on six patients. Marlex mesh was folded into three layers and sandwiched between both ruptured ends that were divided horizontally into two layers in moderate tension. All of the patients showed satisfactory function with a mean follow-up period of 3 years (range, 2.4-3.7 years). The operative procedure is simple because there is no need to harvest healthy tendon or fascia as the donor and there is less adhesion with neighboring tissues and minimal signs of foreign body reactions. PMID- 2910603 TI - Familial diffuse cystic angiomatosis of bone. AB - Twelve cases of diffuse cystic angiomatosis of bone are presented in a family over four generations. The inheritance pattern of the disease appears to be one of an autosomal dominant distribution with no skipped generations and equal sex distribution. Individuals affected are clinically asymptomatic. All blood parameters are normal. Roentgenographically, the lesion occurs throughout the length of long bones and is osteolytic, with a thin sclerotic rim. The cortex of the bone is rarely involved and shows no periosteal reaction. Growth plate closure and remodeling are unaffected. The natural history is of increasing sclerosis, resulting in complete obliteration of the cyst with irregular reactive trabeculations. Although it resembles more serious conditions, the condition can be diagnosed clinically and radiographically, making invasive tests and treatment unnecessary. PMID- 2910604 TI - Prosthetic usage following major lower extremity amputation. AB - There were 157 patients following major lower extremity amputation who were evaluated to determine functional prosthetic ambulation. Twenty-eight patients were evaluated in the amputee clinic and found not to be candidates for prosthetic fitting. Forty-one patients were fit with a prosthesis but did not become functional prosthetic ambulators. Eighty-eight patients became functional prosthetic ambulators. Of all above-the-knee amputees, 46% became functional prosthetic ambulators. Only 19% of bilateral lower extremity amputees became functional prosthetic ambulators. Of all below-the-knee amputees, 66% became functional ambulators. The presence of coronary artery disease decreased the ambulatory potential in above-the-knee or bilateral amputees but not in below-the knee amputees. A screening method for elderly, dysvascular amputees should be instituted prior to prosthetic fitting. PMID- 2910605 TI - Submuscular transposition of the ulnar nerve. AB - A retrospective study of 26 submuscular ulnar nerve transpositions was performed with the specific use of grip and pinch analysis to evaluate this form of objective testing. Twenty-six patients were treated by submuscular transposition of the ulnar nerve between 1981 and 1985 and were followed an average of 21 months. Preoperative and postoperative analysis consisted of subjective questioning, clinical examination, quantitative two-point discrimination, quantitative pinch and grip analysis, and electromyographic (EMG) and nerve conduction velocity (NCV) evaluation. Many of the patients suffered from associated problems such as alcohol abuse, diabetes mellitus, and concurrent Guyon's canal compression, which adversely affected the outcome. Subjectively, 62% were improved, 31% were no better, and 7% were worse. Clinical examination demonstrated 46% improved, 35% no better, and 19% worse. Quantitative two-point discrimination was better in 59%, unchanged in 26%, and worse in 15%. Quantitative pinch and grip analysis revealed 28% improved, 56% with little improvement, or the same, and 16% worse, while EMG/NCV showed one-third of the patients in each category postoperatively. Quantitative pinch and grip analysis provided good preoperative and postoperative documentation, which is absent from previous studies in the literature concerning ulnar nerve transportation. PMID- 2910606 TI - Degenerative joint disease in ballet dancers. AB - Forty-four retired dancers were studied with regard to degenerative joint disease in the lower limbs. Six cases of coxarthrosis were found, significantly more than expected in the general population. In addition, there were four cases of tibio femoral arthrosis, six of knee osteophytosis, four of patellofemoral arthrosis, three of chondrocalcinosis, and one of bilateral ankle arthrosis. More than one half of the dancers had arthrosis in the metatarsophalangeal joints. PMID- 2910607 TI - Accessory nerve palsy following thoracotomy. AB - A previously unreported cause of 11th cranial nerve palsy is described in a 53 year-old man. Dysfunction of the trapezius branch of the spinal accessory nerve occurred following median sternotomy and was documented by electromyography. This injury resulted in dysfunction of the trapezius muscle with loss of support of the shoulder girdle and pain. The injury may have been due to stretching from sternal retraction or injury secondary to internal jugular venous cannulation. PMID- 2910608 TI - Percutaneous lumbar discectomy. Review of 100 patients and current practice. AB - In a prospective study, 100 patients with 102 herniations of the nucleus pulposus at L2-L3, L3-L4, L4-L5, and L5-S1 and unremitting radicular pain were treated by percutaneous lumbar discectomy. Ninety-three patients were available for follow up examination. Three patients had died, and four patients could not be located for this review, but all had been followed for more than one year postoperatively and were judged to have had an excellent result at the time of the last follow-up examination. Fifty-nine patients have been followed for longer than two years postoperatively, with a maximum follow-up period of six years. Evaluations were based on modified MacNab criteria and patient interview, questionnaire, and examination. Eighty-one patients (87%) were judged to be successes, since they were pain-free and had returned to gainful employment and their preinjury activity levels. Twelve patients' operations (13%) were judged to be failures and required repeat surgical procedures at the level of the presenting pathologic condition. Three patients (not included in the follow-up group) died of unrelated causes; they had been followed for a minimum of 15 months postoperatively and were previously judged to have had an excellent result. No major complications, including superficial or deep infections, discitis, or neurovascular compromise, were encountered. Meticulous selection of patients for percutaneous lumbar discectomy is the key to success with the method. PMID- 2910609 TI - Extracorporeal hemolysis in orthopedic patients. Report of two cases. AB - Two patients who had extracorporeal hemolysis of their blood transfusions are reported. In both cases, accidental overheating and hemolysis of the transfused blood caused a gross hemoglobinuria. Because the etiology of the hemolysis was not readily apparent at the time, both patients were managed as though they had had an acute hemolytic transfusion reaction. Because there was no activation of the complement cascade by antigen-antibody complexes, both patients suffered no ill effects. Differentiation of extracorporeal hemolysis from hemolytic transfusion reactions requires a careful inspection of all blood administration equipment, as well as an analysis of the untransfused blood in both bag and tubing. Patients undergoing orthopedic procedures account for 15% of all blood transfused in the United States. Awareness of adverse effects of transfusion is therefore important to orthopedic surgeons. PMID- 2910610 TI - Distal screw targeting of interlocking nails. AB - Successful placement of the distal interlocking screws into the Grosse-Kempf nail is a demanding procedure due in part to deformation of the nail during insertion and to inaccuracy of the targeting device supplied with the system. The authors suggest an alternative approach. After placement of the nail in a tibia or femur, a Kirschner wire (K-wire) is directed through the distal transfixation hole under fluoroscopic control. A second Grosse-Kempf nail is placed alongside the limb with the K-wire passing through the corresponding distal hole. The more proximal hole on the nail serves as a targeting guide for a more proximal wire. Once correct placement of the wires is confirmed roentgenographically, the near cortex is opened with a cannulated drill passed over the wires. The wires are removed, the opposite cortices are drilled, and the screws are placed. In 25 consecutive distally locked nailings (eight tibiae and 17 femora), the technique was easily mastered, decreasing the roentgenogram exposure when compared to freehand techniques. PMID- 2910611 TI - The tension-stress effect on the genesis and growth of tissues. Part I. The influence of stability of fixation and soft-tissue preservation. AB - To evaluate the optimum conditions for osteogenesis during limb lengthening and to study the changes in soft tissues undergoing elongation, a series of experiments were performed on the canine tibia. The experiments used the transfixion-wire, Ilizarov circular external skeletal fixator in configurations of differing stability of fixation in combination with a second variable, i.e., preservation of the periosteum, bone marrow, and medullary blood supply. Both increased fixator stability, and maximum preservation of the periosseous and intraosseous soft tissues enhanced bone formation during limb lengthening. To assess the role that the direction of the elongation vector plays in osteogenesis, canine tibiae were widened rather than lengthened in a second series of experiments using an Ilizarov apparatus modified for lateral distraction. The new bone formed parallel to the tension vector even when perpendicular to the bone's mechanical axis. As in longitudinal lengthening, damage to the bone marrow inhibits osteogenesis occurring by the influence of a lateral tension-stress vector. In a third series of experiments, half- and full circumference cortical defects were created in canine tibiae to study the osteogenic potential of the marrow. New bone formed rapidly, even when the marrow was separated from the surrounding periosseous soft tissues by a sheet of polyvinyl chloride, attesting to the importance of marrow element preservation during osteotomy for limb lengthening. PMID- 2910612 TI - Mycobacterium marinum flexor tenosynovitis. AB - Four culture-positive cases of flexor tenosynovitis of the hand caused by Mycobacterium marinum are reported. The organisms were cultured at 32 degrees. All patients were treated with a combination of flexor tenosynovectomy and antimycobacterial treatment with ethambutol and rifampin. The length of antimycobacterial treatment ranged from nine to 22 months. All four patients responded to treatment with cessation of signs of infection, increased range of motion, and complete wound healing. PMID- 2910613 TI - Adamantinoma of the tibia masked by fibrous dysplasia. Report of three cases. AB - Three cases of adamantinoma of the tibia associated with and mimicking fibrous dysplasia or osteofibrous dysplasia are reported in children aged three, nine, and 16 years. The roentgenographic features were typical of intracortical fibrous dysplasia (osteofibrous dysplasia). These entities are not two distinct diseases, but rather are different histologic expressions of essentially the same process, which varies depending on location (predominantly intracortical or medullary) and age. Adamantinoma in children under ten years of age is not as rare as reported in the literature and was found in two of 14 cases in our files (14.3%). In some cases the fibrous dysplasialike component predominates over the scarce epithelioid islands of tumor cells and consequently is not recognized as adamantinoma. That may explain the frequent recurrences after incomplete excisions of supposed intracortical fibrous dysplasia lesions in young children. An extensive histopathologic study of the biopsy and/or surgical specimen by a specialized pathologist is therefore advisable. PMID- 2910614 TI - Preoperative embolization in the treatment of osseous metastases from renal cell carcinoma. AB - Metastatic lesions due to renal cell carcinoma are frequently hypervascular. This study reports the results of preoperative embolization of skeletal metastases from hypernephroma. Reported for the first time in the English literature is the use of this technique for preoperative devascularization of metastatic lesions to the spine in eight patients. Effective devascularization was achieved in all peripheral lesions. Blood loss for peripheral lesions averaged 940 cc and compared favorably to 20 nonembolized cases, in whom average blood loss was 1975 cc. Spinal embolization requires careful identification and preservation of any segmental arteries that supply the anterior spinal artery. Effective spinal devascularization was achieved in six of eight patients. In two patients significant bleeding occurred as a result of incomplete embolization. This series supports the growing evidence for the efficacy and safety of selective arterial embolization in the preoperative control of hemostasis in patients with metastatic hypernephroma. Embolization of spinal metastases, although technically demanding, has been effective in devascularizing these lesions without serious neurologic complications. PMID- 2910615 TI - Mycobacterium terrae osteomyelitis and septic arthritis in a normal host. A case report. AB - A 48-year-old previously healthy white man had progressive painful swelling of his proximal index finger and the proximal interphalangeal (PIP) joint. A biopsy revealed Mycobacterium terrae septic arthritis and osteomyelitis. Six months of therapy with isoniazid, rifampin, and ethambutol were not accompanied by any improvement and amputation was necessary. PMID- 2910616 TI - Calcar-collar contact and valgus-varus positioning did not affect loosening in their series. PMID- 2910617 TI - Does percutaneous nucleotomy with discoscopy replace conventional discectomy? Eight years of experience and results in treatment of herniated lumbar disc. AB - Percutaneous nucleotomy was first described in 1975 by Hijikata in Japan. In 1979 the present authors adopted this method for the treatment of lumbar disc herniation and modified Hijikata's original instruments. Since 1982 additional intradiscal optical control has been included by means of an adapted arthroscopic kit for more accurate and effective removal of the nucleus pulposus under direct view. This procedure is called discoscopy. Between 1979 and late 1987, the method was applied to 109 patients with lumbar disc herniation. The indications included lumbar sciatica that (1) was resistant to conservative treatment and (2) in which myelography and/or examination by computed tomography proved a disc protrusion without dislocation in the spinal canal. The level most affected was L4-L5. Major operative complications encountered were one vascular lesion and two cases of secondary spondylodiscitis. Clinical results in patients with other additional causes of sciatica, such as spondylolisthesis or relapse of disc herniation, were nearly as favorable as in isolated first-time disc herniation. The overall success rate was 72.5% (79/109 patients). PMID- 2910618 TI - Early experience with percutaneous lateral discectomy. AB - Seventeen patients were treated by percutaneous lumbar discectomy for a herniated disc and sciatica. The criteria for inclusion in this series included: (1) a protruding disc in the lumbar area causing neural compression; (2) persistent sciatica; (3) failure of conservative treatment; (4) magnetic resonance imaging, computer tomographic, or myelographic confirmation of the protrusion; and (5) chronic low-back pain with definite evidence of a protruding disc at the appropriate level. The only contraindication to the procedure is the presence of an extruded fragment. There were ten male and seven female patients, with an average age of 40 years. The operation was performed under local anesthesia and by the method of Hijikata. Six cases were at L5-S1, nine at L4-L5, four at L3-L4, and one at L2-L3. Fourteen of 16 patients were relieved of their symptoms. One operation was aborted due to the inability to pass the cannula beneath arthritic facet joints. One complication occurred early while using general anesthetic. An L5 nerve root was injured, causing a permanent drop foot. Major possible complications include infection, nerve root injury, and vascular injury. The success rate with an average follow-up period of six and one-half months was 87.5%. PMID- 2910619 TI - Percutaneous automated discectomy. A new approach to lumbar surgery. AB - An automated technique for percutaneous lumbar discectomy applies the principle of suction cutting. The indications are leg pain greater than back pain (sciatica) and failure of all conservative therapy. The typical neurological and roentgenographic abnormalities of a contained herniated lumbar disc are mandatory. The procedure is performed with a Nucleotome (Surgical Dynamics, San Leandro, California) that is a specially designed, 2-mm blunt-tipped suction cutting device inserted via a posterolateral approach into the affected disc using fluoroscopic control. The results that can be expected with the technique are similar to chymopapain and are in the 70% success range. Automated percutaneous discectomy has a demonstrably low morbidity and can be performed under local anesthesia on an outpatient basis. PMID- 2910620 TI - Automated percutaneous discectomy at the L5-S1 level. Use of a curved cannula. AB - Previously, a major limitation to percutaneous disc decompression to relieve symptoms of sciatica was the inability to approach the L5-S1 level. Obstruction by the iliac crest prevented the instrumentation from entering the L5-S1 disc space. In this paper, the authors describe a curved cannula which can be placed down to the L5-S1 disc space over a straight trocar that has been anchored at the annulus. The cannula bends the flexible aspiration probe back into the plane of the disc so that it is no longer obstructed by the sacral end plate. Using this system, the L5-S1 disc space was successfully removed in 90% of 30 cases. PMID- 2910621 TI - Early experience with automated percutaneous lumbar discectomy in the treatment of lumbar disc herniation. AB - Seventeen patients with symptomatic lumbar disc herniation were treated with automated percutaneous lumbar discectomy employing local anesthetic in an outpatient setting. Operative technique included (1) intravenous sedation and single-dose antibiotics, (2) prone oblique patient positioning for initial needle placement, and (3) postdiscectomy interspace lavage with bupivacaine hydrochloride. There were no postoperative complications and the procedure was well-tolerated by all patients. Although results have thus far been less successful than previously reported, with improved patient selection by means of routine magnetic resonance imaging (or computed tomographic discography in select cases), success rates (nine of 17 patients) might approach those achieved by chemonucleolysis. The successful response of four patients with so-called midline L4-L5 discs has been particularly encouraging, and it may be that percutaneous lumbar discectomy will be an effective and a reasonable treatment alternative for this particular subgroup of patients. PMID- 2910622 TI - Percutaneous nucleotomy. A new concept technique and 12 years' experience. AB - Lumbar disc herniations and degenerations are very prevalent lesions, and many surgical approaches have been adopted for these conditions. However, the results of conventional or extensive operations have not always been satisfying. In 1975, the author developed the technique of percutaneous nucleotomy in an effort to avoid the major surgeries then employed. Fenestration of the annulus and partial resection of the nuclear substance are achieved percutaneously by a posterolateral approach. Intradiscal pressure is reduced considerably, and relief of irritation of the nerve root or the pain receptors around the disc is obtained. The extraction of the herniated portion of the disc is not achieved by the procedure. However, the amount of herniated disc substance may be reduced by disc decompression with suction. The procedure can be done in a radiology department under local anesthesia and requires 30 to 60 minutes. Of 136 cases followed, 72% of the patients are satisfied. The concept and theoretical considerations, surgical instruments, details of improved technique, results, and complications of percutaneous nucleotomy are introduced and compared with the original technique. PMID- 2910623 TI - Percutaneous removal of herniated lumbar discs. 50 cases with ten-year follow-up periods. AB - L4-L5 herniated discs documented by myelogram were removed percutaneously from 50 patients, under local anesthesia and X-ray control, and the patients were followed for ten years. Forty-three patients (86%) had relief of sciatica and sensory deficit. However, only one out of eight patients who had had motor neurological deficit had return of normal power and relief of sciatica from this procedure. The best clinical results were in those patients who felt improvement and relief of pain in the leg at the time of the removal of the disc material. The best clinical results were in patients with a major bulge of the disc and decompression of the nerve root. Patients with sequestration of the disc do not uniformly respond well to this procedure. There were no significant complications. Percutaneous excision of herniated L4-L5 lumbar discs, under local anesthesia, is a safe and valid procedure to reduce patient morbidity and hospital stay, and it does not prejudice the outcome of a formal laminectomy if it should fail. PMID- 2910624 TI - Clinical commentary. Some thoughts on the treatment of beta hemolytic streptococcal infections. PMID- 2910625 TI - Astasia-abasia. A conversion reaction. Prognosis. AB - Twenty-seven children and adolescents were diagnosed as having astasia-abasia on the basis of a conversion reaction between 1965 and 1979. Follow-up information was obtained by questionnaire or a telephone interview from all but one patient over periods ranging from 5 to 22 years. Twenty-two patients thought that they were in good health, but nine patients had some minor complaints, such as leg weakness or stomach pains. Major symptom substitution had not occurred. No organic illness had been missed. One patient was in psychiatric care, two additional patients seemed to have continued mental problems, and one patient was in jail after having killed his parents. PMID- 2910626 TI - Congenital lobar emphysema. The roles of CT and V/Q scan. AB - An infant with congenital lobar emphysema of the left upper lobe presented with unusually severe mediastinal shift and underwent computed tomography (CT) and radionuclide V/Q scans. The V/Q scan confirmed the non-functioning nature of the hyperinflated lobe while the CT scan depicted the abnormal anatomy as well as the normal morphologic characteristics of the remaining lung thus allowing for safe and appropriate surgical management. PMID- 2910627 TI - Crisis intervention for bereavement support. A model of intervention in the children's school. AB - A crisis intervention consultation service to the schools for bereavement support for children is described. Examples are offered of the author's experience in providing this service to children from the pre-kindergarten to senior high level, at private, parochial, and public schools. These requests were generally in response to tragic deaths of fellow students and significant adults, including teachers, parents, and friends. Suggestions are outlined for pediatric and mental health consultants who may wish to offer similar services within their communities, with particular emphasis on issues to address in program planning and implementation. PMID- 2910628 TI - Articles on child abuse. PMID- 2910629 TI - High prevalence of Trichomona infections in adolescents. PMID- 2910630 TI - Use of povidone-iodine in umbilical cord care. PMID- 2910631 TI - Breastfeeding among low-income, high-risk women. AB - Data from a state supported project providing multidiscipline (clinical social work, nursing, nutrition, obstetrics, and pediatrics) assistance to low-income women judged to be at high perinatal risk by medical and social history were analyzed regarding infant feeding decisions. Data from 2,124 subjects delivered from 1976 to 1985 were available for analysis. The population tended to be single (77%), black (66%), poorly educated (63% less than a high school education), and young (mean age 21.8 years). Thirty-six percent were primiparas. The decision to breastfeed was associated with white race, older maternal age, higher educational level, marriage, and earlier utilization of prenatal care. Prenatal infant feeding plans were compared with actual postpartum decisions for 1,168 women. Only 3 percent of those initially planning to bottle feed changed their minds postpartum and breastfed although 31 percent of those initially planning to nurse ultimately chose artificial feeding. Ten percent of women were initially undecided; one-third of this group ultimately breastfed, two-thirds bottle fed. Overall the percentage of women in the project who were breastfeeding rose from 15 percent to 22 percent from the early to later years of the project (p less than 0.0001). PMID- 2910632 TI - Ovarian cysts in precocious puberty. AB - We describe a 7-year-old girl with precocious puberty in whom a single large cyst (5 cm) and several small cysts (8-10 mm) in the single remaining ovary were detected by the ultrasound examination. Endocrinological examinations confirmed the diagnosis of central precocious puberty. Pathologic findings after the removal of the cystic lesions revealed that the large cyst was derived from degenerated follicular cysts and the small cysts were identical to follicular cysts: all were considered to have been formed by gonadotropin stimulation. In general, surgical removal of an ovarian follicular cyst in central precocious puberty is inappropriate. However, in this unusual patient who had a degenerated large cyst, surgery seemed to be appropriate because of a previously removed teratoma in the contralateral ovary. PMID- 2910633 TI - The pharmacodynamics of diphenhydramine-induced drowsiness and changes in mental performance. AB - The time course of diphenhydramine concentrations and effects on both mental performance and subjective feelings of drowsiness were assessed in 15 healthy men. Subjects received single oral doses of diphenhydramine, 50 mg, and placebo in this double-blind crossover study. Diphenhydramine plasma concentrations and central nervous system actions were assessed for 24 hours after each treatment. Cognitive impairment was assessed with an automobile driving simulator and digit symbol substitution scores, whereas drowsiness was self-assessed on a visual analog scale. Diphenhydramine produced significant feelings of drowsiness for up to 6 hours after the dose, whereas significant mental impairment was apparent for only 2 hours. Despite the difference in duration of these effects, drowsiness and mental impairment have parallel slopes when effects are related to diphenhydramine concentrations. These data suggest that although the apparent diphenhydramine concentration thresholds to produce drowsiness are lower (30.4 to 41.5 ng/ml) than those needed to produce mental impairment (58.2 to 74.4 ng/ml), these effects have profiles consistent with their being manifestations of the same pharmacologic effect. PMID- 2910634 TI - Once-daily dosing decreases renal accumulation of gentamicin and netilmicin. AB - The pathogenesis of aminoglycoside nephrotoxicity is intimately related to the extent of drug accumulated in the renal cortex. In the framework of searching for preventive measures of aminoglycoside-induced nephrotoxicity, we investigated the influence of dosage regimen on the renal cortical accumulation of gentamicin and netilmicin in humans. Patients with a tumor partly involving one kidney, with normal renal function, and scheduled for nephrectomy received one dose of either gentamicin (4.5 mg/kg) or netilmicin (5 mg/kg) as a single short-term infusion or as 24-hour continuous infusion. Treatment started 24 hours before surgery. Serum aminoglycoside pharmacokinetics were examined during treatment and renal cortical tissue was sampled at the moment of operation for drug determination. The short term infusion schedule yielded cortical concentrations of 103.2 +/- 36.3 and 137.4 +/- 34.6 micrograms/gm for gentamicin and netilmicin, respectively. Tissue levels after continuous infusion were 158.1 +/- 52.9 and 178.5 +/- 21.8 micrograms/gm for gentamicin and netilmicin, respectively. For each aminoglycoside, a single short-term infusion resulted in significantly lower renal drug levels than did a continuous infusion of the same dose. From the nephrotoxicity point of view, these data support the administration of gentamicin and netilmicin as once-daily injections. This also supports the appropriateness of further studies to determine clinical efficacy of once-a-day dosing for aminoglycosides. PMID- 2910635 TI - In vitro characterization of the human cytochrome P-450 involved in polymorphic oxidation of propafenone. AB - Propafenone is a new class 1 antiarrhythmic agent. The drug is extensively metabolized. 5-Hydroxylation and N-dealkylation constitute major metabolic pathways. Recently it has been demonstrated that the in vivo metabolism of propafenone is controlled by the debrisoquin/sparteine polymorphism. To elucidate which of the above metabolic reactions is catalyzed by cytochrome P-450db1, the formation of 5-hydroxypropafenone and N-desalkylpropafenone was studied in the microsomal fraction of four human kidney donor livers previously characterized with regard to their ability to hydroxylate the beta-adrenergic antagonist bufuralol. The l'hydroxylation of bufuralol is catalyzed by the P-450db1 responsible for polymorphic debrisoquin/sparteine oxidation. The formation of 5 hydroxypropafenone but not N-desalkylpropafenone was closely related to bufuralol l'hydroxylation. Incubation with LKM1 antibodies, which selectively recognize P 450db1, inhibited 5-hydroxypropafenone formation completely whereas N dealkylation was unimpaired. Propafenone was a strong competitive inhibitor of bufuralol l'hydroxylation. Thus it can be concluded that 5-hydroxypropafenone is formed by the cytochrome P-450 isozyme involved in polymorphic bufuralol oxidation. PMID- 2910636 TI - Dextromethorphan O-demethylation in liver microsomes as a prototype reaction to monitor cytochrome P-450 db1 activity. AB - Liver dextromethorphan O-demethylation to dextrorphan is associated with the debrisoquin type of oxidation phenotype in humans. We studied dextromethorphan oxidation in vitro using human liver microsomes to investigate the kinetics of the polymorphic monooxygenase (cytochrome P-450 db1) and factors that may influence its activity. In microsomal preparations from six extensive metabolizers the reaction parameters were: Michaelis-Menten constant = 3.4 +/- SD 1.0 mumol/L and maximum rate of metabolism = 10.2 +/- 5.3 nmol x mg P-1 x hr-1, vs 48 mumol/L and 2.2 nmol x mg P-1 x hr-1, respectively in microsomes prepared from the liver of one poor metabolizer. The reaction was inhibited by nonspecific monooxygenase inhibitors such as SKF 525-A (Ki = 100 nmol/L) and cimetidine (Ki = 40 mumol/L), by known substrates of the polymorphic isozyme such as [+]-bufuralol (Ki = 7.5 mumol/L), debrisoquin (Ki = 25 mumol/L), and sparteine (Ki = 45 mumol/L), and by the selective cytochrome P-450 db1 inhibitor quinidine (Ki = 15 nmol/L). This assay permits in vitro screening for candidate substrates or inhibitors of the polymorphic isozyme. PMID- 2910637 TI - Altered protein binding of etoposide in patients with cancer. AB - Etoposide plasma protein binding (PB) is reported to be 94% based on in vitro studies using normal human serum albumin (SA). Etoposide PB in 17 patients with cancer receiving etoposide (50 to 100 mg/m2) and in plasma of 14 volunteers was determined by equilibrium dialysis with 3H-etoposide. The unbound fraction (Fu) in patients with cancer was 0.139 +/- 0.099 compared with 0.043 +/- 0.0036 in plasma from normal volunteers (p less than 0.0009; t test). Etoposide binding ratio (BR) was correlated directly with SA (r2 = 0.83; p less than 0.05). In the population with cancer Fu was significantly correlated with bilirubin (r2 = 0.837; p less than 0.05). In a multivariate analysis, SA and bilirubin were significant predictors of Fu (r2 = 0.93; p less than 0.05). This study corroborates previous reports of etoposide PB in normal human serum and demonstrates altered PB in patients with abnormal serum albumin or bilirubin levels. PMID- 2910638 TI - Intravascular mixing and drug distribution: the concurrent disposition of thiopental and indocyanine green. AB - The dispositions of concomitantly administered indocyanine green (ICG) and thiopental were determined in 12 patients undergoing general anesthesia and surgery. These were best characterized by a two-compartment ICG model and a four compartment thiopental model, chiefly because of data obtained from frequent early arterial blood samples. The models had a common central volume (V1), and the peripheral ICG compartment was the subset of a peripheral thiopental compartment. The two-compartment ICG model described its mixing within the intravascular space. The traditional VC of three-compartment models of thiopental disposition is described by the present four-compartment model as an initial distribution volume, V1, codetermined by ICG as central blood volume, and a rapidly equilibrating peripheral volume, V4. The combined simultaneous ICG thiopental model more clearly reflects physiology than do the results of earlier curve-fitting techniques and may be useful in studying the pharmacokinetic basis of altered reactivity to thiopental. PMID- 2910639 TI - Propranolol's metabolism is determined by both mephenytoin and debrisoquin hydroxylase activities. AB - The relative contributions of the debrisoquin and mephenytoin isozymes of hepatic cytochrome P-450 to the stereoselective metabolism of propranolol have been studied in a panel of volunteers of known oxidative phenotypes. Six subjects were extensive metabolizers of both debrisoquin and mephenytoin (EM). Four subjects were poor metabolizers of debrisoquin but rapid for mephenytoin (PMD). Five subjects were poor metabolizers of mephenytoin but rapid for debrisoquin (PMM), and one individual had a deficiency for both test compounds (PMD/M). Partial metabolic clearances of each propranolol enantiomer to 4-hydroxypropranolol (4-OH P), the sulfate, and glucuronide conjugates of 4-OH-P, naphthoxylactic acid (NLA) and propranolol glucuronide, were estimated after a single oral dose of racemic propranolol (80 mg). The partial metabolic clearance of both enantiomers to total 4-OH-P in the PMD group was 75% less than in the EM and PMM groups, indicating the contribution of the debrisoquin isozyme to this route of metabolism. The R/S ratios for the clearance to 4-OH-P were similar between EM and PMD (2.5 +/- 0.5 vs 2.5 +/- 0.4, respectively), implying that the different enzymes involved in ring hydroxylation (i.e., the debrisoquin isozyme and other hydroxylases) have similar stereoselective preferences. The partial metabolic clearance to NLA was 55% less in the PMM group than in the EM and PMD groups, indicating that S mephenytoin 4-hydroxylase contributes to the metabolic conversion of propranolol to NLA. The R/S ratios for the clearance to NLA were close to unity in all groups. The partial metabolic clearance to propranolol glucuronide also did not exhibit stereoselectivity and was similar in all groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2910640 TI - Oral dipyridamole increases plasma adenosine levels in human beings. AB - Plasma adenosine levels in five healthy volunteers for 5 consecutive days showed far less intrasubject than intersubject variation (p less than 0.0001), indicating that plasma adenosine levels are relatively constant during this period. Plasma adenosine levels were then measured in a different group of five healthy subjects for a 5-day control period and during a 5-day course of oral dipyridamole at a dose of 100 mg every 6 hours. Intrasubject comparisons showed that plasma adenosine levels were significantly higher during the 5 days of dipyridamole administration than during the control period (p = 0.017) and that this increase was most significant after 48 hours of drug (p less than 0.001) administration. The average increase was 0.133 mumol/L (60%) with a range of 0.063 to 0.197 mumol/L (37% to 212%) during the last 3 days. A significant positive correlation was noted between plasma adenosine and dipyridamole levels (p = 0.001). We conclude that adenosine levels are relatively stable for an individual and are maximally increased after 2 days of oral dipyridamole. PMID- 2910641 TI - Slow-paying patients. PMID- 2910642 TI - Record release. General guidelines. PMID- 2910643 TI - Project to address adverse outcomes of diabetes and pregnancy. PMID- 2910644 TI - March toward nursing excellence. PMID- 2910645 TI - Vascular changes in the human endometrium following the administration of the progesterone antagonist RU 486. AB - Eleven healthy women were assigned to one of two groups. They received 50 mg RU 486 orally per day either on cycle days 7 to 10 (preovulatory group n = 5) or on cycle days 20 to 23 (postovulatory group, n = 6). An endometrial biopsy was taken on the fourth day of the RU-treatment in the preovulatory group and on the second (n = 2) or fourth (n = 4) treatment day in the postovulatory group. Biopsies from 34 untreated women representing matched samples from early and mid preovulatory phase (n = 10) and mid and late postovulatory phase (n = 24) were used as control. The ultrastructure of the endometrial capillaries was investigated by morphometric methods. The administration of RU 486 during the preovulatory phase did not modify the vascular structure. However, when given in the postovulatory phase, necrosis occurred in the capillary endothelial cells with and without regressive changes of the adjacent stroma. The area and diameter of the capillary lumen and the area of the adventitia was smaller than in the control material (p less than 0.01). The result of the study suggests that RU 486, when administered in the postovulatory phase, directly affects the capillary vessels of the endometrium. PMID- 2910647 TI - Lack of metabolic effects of a triphasic formulation containing norethindrone in normal women studied prospectively. PMID- 2910646 TI - Effect of low-dose oral contraceptives on natural killer cell activity. AB - Several reports indicate an association between oral contraceptives and increased infection rates. One mechanism that could explain this increased infection rate is a decrease in immune function. A study comparing T cell subsets showed no differences in numbers between oral contraceptive users and controls. In this study, natural killer cell activity was compared in women before and 3 and 6 months after oral contraceptive use. There was a statistically significant decrease in NK cell activity after three months. There was no further decrease by six months and the differences were no longer significant due to greater variability. No infections were reported during the study period. Thus, the observed reduction in NK activity was either physiologically insignificant or the previously reported increase in infections may be the result of non-immunological factors. PMID- 2910649 TI - Virus inactivation in plasma products. PMID- 2910648 TI - Plasma reduced and total ascorbic acid in healthy women: effects of smoking and oral contraception. AB - This is the first report of both reduced (RAA) and total (TAA) plasma ascorbic acid levels in women who smoke and are on oral contraception. 155 normal healthy subjects were investigated. A study questionnaire was completed including age, method of contraception, smoking status, and food intake at breakfast, prior to attending the clinic. Biochemical assays were promptly carried out without knowledge of subject's clinical or dietary status. One-way analysis of variance revealed that oral contraception per se, barrier or IUD methods have no effect on plasma ascorbic acid levels. The mean values (mg/dl +/- SD) for plasma RAA between smokers and nonsmokers were 0.512 +/- 0.241 and 0.601 +/- 0.263; and that for TAA were 0.565 +/- 0.232 and 0.682 +/- 0.231, respectively. Significant decreases in both plasma RAA (p less than 0.05) and TAA levels (p less than 0.001) were observed in smokers. Age was an interacting variable. No association of smoking or oral contraceptive use was seen with RAA or TAA levels among women less than 26 years, but decreases in both RAA and TAA levels were evident among smokers aged 26 years or older. The present study emphasizes the total exposure to smoking, e.g., pack years, is a significant confounding variable in the study of plasma ascorbic acid levels. PMID- 2910651 TI - Strategies to produce virus-safe blood derivatives. PMID- 2910650 TI - Virus inactivation by addition of neutralizing antibodies. AB - This study has shown that the principle of virus neutralization by specific antibodies is feasible at least in the case of hepatitis B. Virus neutralization is our preferred method since it entails no loss of functional activity and no risk of induction of neo-antigens in the plasma derivatives. Although double blind clinical trials have not been performed, this study--in combination with some other studies - brought the conclusive evidence that virus neutralization in the case of hepatitis B transmission is efficacious. The suggested occurrence of side effects related to the formation of immune complexes during or after administration is not borne out by more than 7 years of experience with neutralized plasma derivatives with no reported side effects. Whether this method is useful for other viruses will depend on the availability of specific neutralizing antibodies. PMID- 2910652 TI - Virus inactivation/elimination in therapeutic protein concentrates. AB - Concern for virus transmission from intravenous biological products, derived from natural and biotechnological sources, has prompted us to investigate various methods for virus inactivation while preserving the biological activity of the therapeutic entity. This concern is currently acute regarding the presence of HIV in purified human plasma protein concentrates. Four different methods of virus removal (1) heating in solution; (2) use of lipid solvents; (3) low pH treatment, and (4) partitioning during purification, are reported for various plasma proteins that have been spiked with model viruses. General virus inactivation strategies for therapeutic protein concentrates are discussed. PMID- 2910653 TI - Inactivation of viruses with 1,10-phenanthroline. PMID- 2910654 TI - Epidemiology of constipation in the United States. AB - In the present study, the epidemiology of constipation in the United States and an assessment of its impact on national health are presented. This analysis was based on four different surveys, i.e., the National Health Interview Survey, the National Hospital Discharge Survey, the National Ambulatory Medical Care Survey, and the Vital Statistics of the United States. These surveys have estimated that over 4 million people in the United States have frequent constipation, corresponding to a prevalence of about 2 percent. Constipation was the most common digestive complaint in the United States, outnumbering all other chronic digestive conditions. Cathartics and laxatives were prescribed to 2 to 3 million patients yearly by general and family practitioners or internists. In 92,000 annual hospitalizations, constipation was listed among the discharge diagnoses. About 900 persons die annually from diseases associated with or related to constipation. Constipation was three times more common in women than men. It showed a marked increase after the age of 65 years. It appeared to affect nonwhites 1.3 times more frequently than whites. In addition, constipation was more frequent in people living in the South than elsewhere in the United States, and in people from families with low income or brief education of the head of family than in people from families with high income or a high educational level of their family head. These data suggest that there are other factors involved in the cause of constipation in addition to dietary fiber content and psychogenic influences. The frequent occurrence of constipation and its impact on public health stress the need for further studies devoted to the epidemiology and basic pathophysiology of this condition. PMID- 2910655 TI - Site distribution of carcinoma of the large intestine. Retrospective study of 600 cases. AB - The site distribution of large-bowel adenocarcinomas was studied in a retrospective study compromising 600 patients. These patients were divided into two groups according to the year of their operation; group A included patients operated upon between 1978 and 1982, and group B patients were operated upon between 1983 and 1987. Comparing these two five-year periods, a statistically significant increase in the incidence of right colon tumors was noted (P less than 0.05). There was no difference in the distribution pattern of the carcinomas according to sex or age between the two groups (P less than 0.1). The shift to the right of large-bowel neoplasms may indicate the need for an alteration of the diagnostic procedures concerning this disease, with more emphasis given to total colonoscopy and or double-contrast barium enema. PMID- 2910657 TI - A model to evaluate acute and chronic stress in the colonic mucosa of rats. AB - The effect of acute and chronic stress on the colonic mucosa of the rat was investigated at various time intervals, ranging from one day to eight weeks. The amount of DNA synthesized by the mucosa was used as a marker of time-related events. A total of 75 Sprague-Dawley rats were investigated. Acute stress was considered for rats briefly plunged (psychic stimulus) or swimming for two hours (physical stimulus). Chronic stress was determined when rats were briefly plunged or swam for two hours for periods ranging from one to eight weeks. "Sham transported" rats were used as controls. DNA in the descending colon decreased significantly in rats swimming for two weeks, but increased (even for plunged rats) at four and eight weeks. In the ascending colon, a substantial increase in DNA content was found in rats plunged or swimming for eight weeks. The descending colon appears to be quantitatively more affected by various stressors than the ascending colon. It is apparent that, in control rats, the mucosa of the descending colon differs from the ascending colon. Fluctuations in the colonic DNA synthesis throughout the experiment suggest that this phenomenon may be connected to compensatory mechanisms toward cell adaptation to stress conditions. The model may prove of value in studies of the therapeutic abrogation of the fluctuations of the DNA replication of the colonic mucosa during the acute and chronic phases of a given stress. PMID- 2910656 TI - Metronidazole vs. erythromycin, neomycin, and cefazolin in prophylaxis for colonic surgery. AB - A prospective, double-blind, randomized study was undertaken to compare perioperative parenteral metronidazole and erythromycin, One neomycin, and cefazolinhundred fifty-five patients were randomized into two groups by the pharmacy department. The resulting difference between the overall septic complication rate in patients receiving erythromycin, neomycin, and cefazolin (10.9 percent) and the rate in patients receiving metronidazole alone (31.9 percent) was significant. This indicates that an antibiotic to cover aerobic bacteria should be added to the regimen when metronidazole is used. PMID- 2910658 TI - Safe resection for diverticular disease of the colon. AB - A retrospective study of 83 patients undergoing surgery for diverticular disease over two years at a colorectal specialty hospital was undertaken to assess the safety of resection. No patient had free perforation. Eighty-nine percent of 46 patients with neither abscess nor fistula underwent resection and primary anastomosis, the remainder undergoing other resectional therapy; there was no mortality in this group. Of the 37 patients with abscesses, fistulas, or both, all had resections with or without primary anastomoses and one of these 37 patients died (2.7 percent mortality). In the entire series of 83 patients, the operative mortality was 1.2 percent, although 69 percent had morbidity. Resection can be performed safely for diverticulitis, and primary anastomosis can be safely added in uncomplicated and selected complicated cases. PMID- 2910659 TI - Sphincter repair for fecal incontinence. AB - Twenty-seven patients who had sphincter repair by one surgeon over the last ten years were reviewed. Previous surgery, childbirth, and perineal trauma were the most common causes. Twelve patients had been treated previously using an anal continence device (N = 6), postanal repair (N = 5), and rectopexy (N = 1). A covering colostomy was used in ten patients. At the initial operation only 7 patients were rendered completely continent, 13 others were improved, but results were poor in the other 7. Four of the 7 patients were rendered completely continent after secondary operations. Maximum anal pressure and maximum squeeze pressure did not change significantly after surgery; however, preoperative maximum squeeze pressure in patients who achieved complete continence was significantly greater than in those that did not. Poor results usually were associated with severe obstetric trauma. PMID- 2910660 TI - Topography of the inferior rectal artery: a possible cause of chronic, primary anal fissure. AB - The authors believed that it might be possible to explain the local frequency of the anal fissure at the posterior commissure by an anatomic relationship, and examined the blood supply of the anus. The inferior rectal artery is demonstrated by postmortem angiography and by manual preparations (N = 41) and histologic study after angiography of the vessels (N = 10). The blood supply at the different sites of the anal canal are demonstrated by a morphometric study (N = 20). The inferior rectal artery presents two variants in the postmortem angiographies, type 1 (85.4 percent) and type 2 (14.6 percent). In type 1, the posterior commissure is less perfused than the other sections of the anal canal. In addition, the blood supply may be more compromised by contusion of the vessels passing vertically through the muscle fibers of the sphincter ani internus muscle during increased sphincter tone. The role of topography in the pathogenesis of the primary anal fissure is illustrated in a model. PMID- 2910661 TI - Quantitative electron microscopic study on grades of atypia in adenomas of the human large bowel. AB - Clarification of the ultrastructural features of the three different grades of histologic atypia of adenomas (i.e., mild, moderate, and severe atypia) with reference to carcinoma of the human colon and rectum was undertaken using electron microscopic quantitative analysis. Ten normal epithelia, 36 adenomas (14 with mild atypia, 13 with moderate atypia, and 9 with severe atypia) and 14 carcinomas (well-differentiated adenocarcinoma) were examined with light and electron microscopes. Although it has been generally accepted that malignant transformation of an adenoma gradually proceeds with increasing atypia, using light microscopy, ultrastructural quantitative analysis clearly revealed that fine features of individual atypia did not correspond with histologic grades of atypia. Ultrastructural changes occurred abruptly in moderate atypia and showed similar cellular characteristics to carcinoma cells. Mild atypia was almost similar in appearance to normal epithelial cells. Striking changes in the moderate atypic cells were plane apposition of the cell membrane, decrease of the desmosomes, and increase of the lysosomes. These atypical cells were assumed to play a significant role in the adenoma-carcinoma sequence. Therefore, radical surgical therapy would be required for moderate atypic adenoma of the large bowel that is difficult to remove endoscopically. PMID- 2910662 TI - Traumatic perforation of ileal pouch. Report of a case. AB - A 28-year-old woman with a previous history of restorative proctocolectomy for complicated ulcerative colitis had acute onset of severe abdominal pain that was diagnosed at another hospital as a perforated peptic ulcer. Careful history taking revealed that she had blunt trauma to the abdomen one day before admission. Laparotomy detected a perforation hole at the afferent loop of the ileal pouch. Debridement and primary closure of the perforation, with temporary decompression of the pouch, resulted in a good outcome. With the increasing popularity of selecting restorative proctocolectomy for the treatment of polyposis coli and ulcerative colitis, more and more pouches will be constructed. Possible perforation of the ileal pouch should be considered when such patients present with a perforated hollow viscus. With appropriate management, the pouch can be saved. Review of the literature revealed no similar reports. PMID- 2910663 TI - Seminal vesicle-rectal fistula. Report of a case. AB - A previously unreported complication of low anterior resection of the rectum, seminal vesicle-rectal fistula, was encountered one month after surgery in an elderly patient with adenocarcinoma of the midrectum. Antibiotic-induced colitis in the immediate postoperative period led to anastomotic leakage with abscess formation and ensuing fistulization to the surgically denuded right seminal vesicle. Pneumaturia, bacteriuria, and right testicular pain were treated by cutaneous vasostomy and antimicrobial therapy. Despite recurrent low-grade urinary sepsis controlled by alternating courses of various antimicrobials, and radiation therapy for local tumor recurrence, the patient remained reasonably healthy until his death two years later due to stroke associated with cerebral metastases. PMID- 2910664 TI - Kaposi's sarcoma of the colon in a young HIV-negative man with chronic ulcerative colitis. Report of a case. AB - In the United States, visceral Kaposi's sarcoma most commonly occurs in association with the acquired immune deficiency syndrome (AIDS). The authors report a unique case of primary colonic Kaposi's sarcoma in a young heterosexual HIV-negative man with chronic ulcerative colitis. PMID- 2910665 TI - Povidone-iodine enema as a preoperative bowel preparation for colorectal surgery. A bacteriologic study. AB - To evaluate the effects of povidone-iodine (PI) enema on the bacterial flora of colorectal mucosa, the authors studied 113 patients who were candidates for colorectal surgery. The study of the rectum included 72 patients. Total bacterial concentrations after a PI enema (N = 44) were significantly lower than after a simple water enema (N = 12, P less than 0.001), or than after a water enema associated with intravenous metronidazole (N = 16, P less than 0.01). The study of the colon included 41 patients. Total bacterial concentrations did not differ after a PI enema (N = 24) than after a water enema (N = 11); both groups were associated with intravenous metronidazole. In contrast, both preparations significantly reduced bacterial concentrations when compared with oral administration of polyethyleneglycol (N = 6, P less than 0.01). Similar results were observed in rectal and colonic studies, when analysis was restricted to the anaerobic flora. PI is an antiseptic that, when administered alone in an enema or in association with metronidazole, significantly reduces bacterial concentrations in the mucosa of the colon and rectum. It may be proposed as a simple preoperative preparation for colorectal surgery. PMID- 2910666 TI - Neuromuscular and vascular hamartoma of the small bowel. AB - Neurovascular and muscular hamartoma is an unusual benign neoplasma of the small intestine. The clinical and pathological features of this lesion, which we recently encountered in a 91-year-old male, are the subject of this report and are discussed in the context of previously described cases. PMID- 2910667 TI - Clinicopathological study of a patient with idiopathic villous atrophy and small vessel alterations of the ileum. AB - Ileal villous atrophy with normal proximal small intestinal mucosa is a rare lesion observed in a few diseases. We report here a case of unknown etiology. A 49-year-old woman presented with chronic diarrhea and steatorrhea due to bile acid malabsorption which was strikingly improved by a low-fat diet. Villous atrophy was total or subtotal, but enterocyte alterations were minimal. Crypts were hyperplastic and the lamina propria was infiltrated by lymphocytes and plasma cells mainly synthesizing IgM. These alterations were associated with the presence in the submucosa, and occasionally in the mucosa, of numerous convoluted nonectasic capillary tufts. Thrombi consisting of pure platelet aggregates were found in the capillary tufts and adjacent small vessels, whose walls were either normal or hyalinized. The patient suffered for many years from attacks of Raynaud's phenomenon and platelet aggregation was depressed in the presence of collagen. Thrombi disappeared after aspirin treatment, but the other lesions persisted at the time of death from an unrelated cause. PMID- 2910668 TI - Crohn's disease complicated by idiopathic central serous chorioretinopathy with bullous retinal detachment. AB - A case of idiopathic central serous chorioretinopathy with bullous retinal detachment occurring in a patient with Crohn's disease is described. This rare eye condition (36 reported cases in the world's literature) has previously been seen in association with ulcerative colitis, and its occurrence in a patient with Crohn's disease suggests that it may represent another ophthalmologic complication of inflammatory bowel disease. PMID- 2910669 TI - Intestinal neuronal degeneration in a patient with chronic idiopathic intestinal pseudoobstruction. AB - Neuropathological examination of the gut in a patient with chronic idiopathic intestinal pseudoobstruction and temporal lobe epilepsy showed a degeneration of Auerbach's and of Meissner's plexus. The extent of generative changes increased in an aboral to oral direction. Neuronal degeneration was characterized by ballooning of the cytoplasm of the ganglial cells, by a hyperargyrophilia, a shortening and dilation of cell processes, and a progressive fragmentation and loss of axons. In rectal biopsies, a PAS-positive granular material was detected in the cytoplasm of ballooned ganglial cells. A severe peripheral neuropathy with fiber degeneration in the posterior columns and axonal lesions within ventral nerve roots and a more recent fiber degeneration in the lateral columns corresponding to the picture of subacute combined degeneration of the spinal cord and a symmetrical Ammon's horn sclerosis was present. This case of progressive intestinal neuronal degeneration of unknown origin is a newly described condition leading to chronic idiopathic intestinal pseudoobstruction. PMID- 2910670 TI - Intestinal disaccharidases assessed in congenital asucrasia by differential urinary disaccharide excretion. AB - A patient with congenital asucrasia was investigated using in vivo differential urinary disaccharide excretion. Impaired hydrolysis of sucrose and isomaltose, but normal lactase activity, were demonstrated and confirmed by in vitro estimation. The technique of differential disaccharide excretion can now be used to assess three disaccharidases simultaneously, in vivo, including isomaltase. PMID- 2910671 TI - Plugged liver biopsy in patients with impaired coagulation. AB - Histology is of paramount importance in the investigation of hepatic disease but conventional percutaneous liver biopsy is contraindicated when coagulation is significantly impaired. We have used a modified percutaneous approach with plugging of the needle track in 100 patients with vitamin K-resistant prolongation of prothrombin time up to 12 sec above control values or platelet counts as low as 20 X 10(9)/liter. All were successful, and there were no serious complications. The technique is straightforward and is a feasible alternative to the more complex transvenous approach. PMID- 2910672 TI - Inadvertent diagnosis of pheochromocytoma after endoscopic premedication. AB - Hypertensive crisis in a patient with pheochromocytoma can be induced by endoscopy premedication. Opiates, glucagon, and metoclopramide are commonly used in the gastrointestinal laboratory and capable of releasing catecholamines from a pheochromocytoma. Patients who have just had endoscopy can display untoward effects such as nausea, weakness, and diaphoresis. Such patients should probably have their blood pressure carefully recorded. Although hypotension is expected, endoscopists should be alert to the finding of severe hypertension and consider pheochromocytoma. The need for this becomes even greater considering that primary gastrointestinal endoscopy is often being done in doctor's offices away from hospitals and more acute resuscitative resources. In the case reported, a life threatening hypertensive crisis was induced by fentanyl. The hypertensive crisis was correctly ascribed to pheochromocytoma, enabling institution of lifesaving treatment. PMID- 2910673 TI - Chlamydial ascites. AB - Currently, Chlamydia is a major cause of pelvic inflammatory disease (PID), which can be complicated by perihepatitis. Our patient presented with ascites secondary to Chlamydia infection and responded well to treatment with tetracycline. Since Chlamydia infection is becoming more prevalent in the United States, it should be considered in the differential diagnosis of ascites in all young sexually active females. PMID- 2910674 TI - Humoral hypercalcemia complicating adenosquamous carcinoma of the proximal colon. AB - Hypercalcemia as a complication of carcinoma of the colon is uncommon (1). It usually occurs in the presence of anorectal or rectal carcinoma that metastasizes to the lumbosacral vertebrae (2-4). Hypercalcemia complicating colon carcinoma in the absence of bone metastases--so-called humoral hypercalcemia of malignancy or paraneoplastic hypercalcemia--is rare. Only two such cases associated with adenocarcinoma of the colon (5,6) and two cases associated with adenosquamous carcinoma of the distal colon (rectum and sigmoid) (7) have been reported. We describe the first reported case of an adenosquamous carcinoma of the cecum and ascending colon that was accompanied by severe humoral hypercalcemia. The hypercalcemia was associated with a parathyroid hormone (PTH)-like substance. PMID- 2910675 TI - Clostridium difficile colitis secondary to intravenous vancomycin. AB - Nearly every known antibiotic has been implicated as a cause of Clostridium difficile colitis. We report the first case resulting from monotherapy with intravenous vancomycin. The patient was on chronic hemodialysis and was treated with intravenous vancomycin for presumed cervical osteomyelitis. After 29 days of therapy he developed abdominal pain and diarrhea and his stool was found to contain both C. difficile and cytotoxin. The patient responded with symptomatic and microbiological recovery to withdrawal of the drug and treatment with oral metronidazole. The prolonged elevation of serum vancomycin levels in patients with renal failure may predispose them to the development of C. difficile colitis. PMID- 2910676 TI - Nifedipine and gastric emptying. PMID- 2910677 TI - Relationship of biliary pressure to cholangiovenous reflux during endoscopic retrograde balloon catheter cholangiography. AB - In 32 patients undergoing endoscopic retrograde cholangiography with a balloon catheter, culture of bile, biliary pressure at maximal visualization of the biliary tract with iodinated contrast medium, serum iodine concentrations, and blood cultures before and after the procedure were obtained. There was a significant increase in the serum iodine concentration in five of nine patients (55.6%) with pressure between 22 cm H2O and 30 cm H2O and in nine of 13 patients (69.2%) with pressure above 30 cm H2O, while it remained low in 10 patients with pressure below 22 cm H2O. Two patients showed positive blood culture after the procedure, which yielded the same organisms as found in the bile. The biliary pressures in these two patients were 30.4 cm H2O and 38.0 cm H2O. These data suggest that during retrograde balloon catheter cholangiography: (1) cholangiovenous reflux of contrast medium develops with biliary pressure higher than 22 cm H2O, (2) the indicence of the cholangiovenous reflux increases as the pressure is elevated, and (3) regurgitation of bacteria occurs with pressure greater than 30 cm H2O. These findings are noteworthy because the number of patients who need direct cholangiography is increasing. PMID- 2910678 TI - Species-specific effects of neurotensin on gallbladder contraction in vitro. AB - We have previously shown that an in vivo administration of neurotensin (NT) stimulates contraction of dog gallbladder (GB), but produces dilatation of GB in humans. The objective of this study was to examine the effect of NT on human, dog, guinea pig, and rabbit GB in vitro, in order to delineate direct versus indirect actions of NT in different species and to evaluate the structure activity relationships of NT. The effect of NT on the canine sphincter of Oddi (SOD) was also examined in vitro. Isolated longitudinal strips of GB from the four species given above and SOD from dogs were suspended in oxygenated Krebs buffer, and the isometric tension responses to various doses of NT, NT 8-13, NT 1 11, and xenopsin (XP) were determined. All the NT homologs, except NT 1-11, stimulated contraction of the dog GB and SOD in a dose-dependent manner. NT also caused dose-related stimulation of GB contraction from guinea pigs but did not stimulate or depress the contractile activity of human and rabbit GB strips. These results suggest that NT action on GB contraction is species-specific. Tetrodotoxin did not modify the contraction of dog GB and SOD in response to NT, indicating that NT mediates its contractile effects directly. The relaxing effect of NT on GB of humans in vivo, as previously reported by us, thus appears to be an indirect action.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2910679 TI - Effect of tamoxifen on hepatic regeneration in male rats. AB - A number of metabolic changes within the liver occur concurrent with hepatic regeneration. These processes suggest that the administration of an antiestrogen might alter the rate of hepatic regeneration. To examine this question, male Wistar rats were treated with tamoxifen (0.1 mg/rat/day or 1.0 mg/rat/day) or vehicle for three days prior to and after partial hepatectomy, and the anatomic and biochemical process of hepatic regeneration was assessed. Tamoxifen administration caused a dose-dependent decrease in the hepatic cytosolic estrogen receptor activity and, conversely, a dose-dependent increase in cytosolic androgen receptor activity. Despite these changes in baseline hepatic sex steroid receptor status, all receptor activities were comparable between the three groups within 24 hr of partial hepatectomy. Moreover, no differences in any of the parameters assessing hepatic regeneration following partial hepatectomy were evident: liver-body ratio, ornithine decarboxylase activity, and thymidine kinase activity. This lack of effect of tamoxifen treatment on hepatic regeneration suggests either that estrogens do not play a role in the modulation of liver growth after partial hepatectomy or that, once initiated, the regenerative process per se determines a series of events that regulate hepatocellular sex hormone receptor status independent of extrahepatic stimuli. PMID- 2910680 TI - Chronic alcoholism and evolution of pain and prognosis in chronic pancreatitis. AB - To evaluate the influence of chronic alcoholism on clinical features of chronic pancreatitis in Japan, pain evolution, pancreatic insufficiency, and long-term prognosis were studied by comparing chronic alcoholic pancreatitis (N = 88) with idiopathic pancreatitis (N = 67). The 155 patients with known course of the disease over three years were followed-up further for five more years, and pain evolution was evaluated once at the start and once at the end of the follow-up period. At the time of diagnosis, severe pain (59 vs 33%, P less than 0.001), pancreatic calcification (63 vs 31%, P less than 0.001), advanced exocrine pancreatic insufficiency (72 vs 60%, NS), and overt diabetes (48 vs 17%, P less than 0.001) were more common in alcoholic than in idiopathic pancreatitis, respectively. Pain evolution was similar in both pancreatitis, and the pain decreased with time. The rate of abstinence was higher in groups with pain relief than without in alcoholic pancreatitis. Cumulative mortality rate during the five years was higher in alcoholic than idiopathic pancreatitis (26 vs 10%, P less than 0.01). These results suggest more favorable evolution of the disease can be expected by abstinence from alcohol. PMID- 2910681 TI - Effect of intravenous glucagon and glucagon-(1-21)-peptide on motor activity of sphincter of Oddi in humans. AB - Glucagon-(1-21)-peptide, the peptide containing the amino acid sequence (1-21) of glucagon, has the same spasmolytic effect as the complete molecule, without its metabolic action. The effect of glucagon and glucagon-(1-21)-peptide on sphincter of Oddi motor activity was evaluated in 20 patients undergoing ERCP and endoscopic biliary manometry. Glucagon produced a nonsignificant decrease in basal pressure, but significantly reduced both frequency and amplitude of phasic activity of the sphincter of Oddi. Glucagon-(1-21)-peptide showed no effect on basal pressure and amplitude of phasic activity, but provoked a significant reduction of frequency of phasic contraction. PMID- 2910682 TI - Accuracy of abbreviated manometry in detecting esophageal motility abnormalities. AB - We determined whether an abbreviated motility study that is commonly employed in clinical esophageal manometrics was as accurate as an extended manometric evaluation in detecting abnormalities in the esophageal body. One hundred patients underwent both abbreviated (stationary catheter, 10 wet swallows) and extended manometries (stepwise catheter withdrawal, 62 +/- 1 wet swallows). Classification by the two techniques was identical in 83 patients. Abbreviated manometry failed to recognize nine abnormal motility patterns. The abbreviated method was least accurate in the identification of intermittent and focal motility abnormalities (sensitivity = 0.50). Misclassifications were related to catheter position and not solely to differences in the total number of swallows. Of the individual wave parameters measured by each method, detection of multipeaked contraction waves was the most discrepant (R = 0.59). These findings indicate that abbreviated esophageal manometry is reasonably well correlated with a more extended method in detecting esophageal motility disorders and, because of its relative simplicity, appears appropriate for use in clinical practice. Errors related to stationary recording port positions may interfere with the overall accuracy of the abbreviated technique. PMID- 2910683 TI - Reliability of 24-hour home esophageal pH monitoring in diagnosis of gastroesophageal reflux. AB - Twenty-four-hour home esophageal pH monitoring is proposed in order to study gastroesophageal reflux (GER) so that prolonged use of costly hospital equipment and staff can be curtailed and the diagnostic accuracy of the examination improved. Eighty-six patients affected by GER symptoms and 20 healthy volunteers underwent 24-hr home esophageal pH monitoring, x-rays, and endoscopy of the upper gastrointestinal tract to investigate reliability of outpatient recording. Fifteen more patients consecutively underwent out- and inpatient recording to detect possible differences between these methods in the two daily periods. Outpatient monitoring was well tolerated in 94.7% of the patients; 14.3% of them markedly reduced their routine activities. The range of normality of outpatient recording does not differ from that of inpatients. In the 15 patients who consecutively underwent out- and inpatient monitoring, no significant differences were reported. The sensitivity of 24-hr home esophageal pH recording is 0.85, the specificity 1, the accuracy for negative prediction 0.68, and the accuracy for positive prediction 1. The reliability of 24-hr home esophageal pH monitoring is comparable to inpatient recording. It allows hospital cost reduction and is also better tolerated by patients but has not greatly improved the diagnostic accuracy of the gastroesophageal reflux pH monitoring. PMID- 2910684 TI - Stress induces alteration of esophageal pressures in healthy volunteers and non cardiac chest pain patients. AB - The present study was designed to explore the relationship between psychological stress and esophageal motility disorders. Nineteen non-cardiac chest pain patients (10 with the nutcracker esophagus and nine with normal baseline manometry) and 20 healthy control subjects were administered two acute stressors: intermittent bursts of white noise and difficult cognitive problems. The results indicated that the esophageal contraction amplitudes and levels of anxiety related behaviors of non-cardiac chest pain patients and control subjects were significantly greater during the stressors than during baseline periods. All patients demonstrated significantly greater (P less than 0.01) increases in contraction amplitude and anxiety-related behavior during cognitive problems than during the noise stressor. The nutcracker esophagus patients showed a greater increase in contraction amplitude during the problems (23.50 +/- 9.42 mm Hg, X +/ SE) than control subjects (P less than 0.01), while the amplitude changes of chest pain patients with normal baseline manometry were not significantly greater than that of control subjects (9.00 +/- 1.91 mm Hg). The present results identified an increase in contraction amplitude as the primary esophageal response to stress. The possible interaction of esophageal contraction abnormalities, psychological stress, and the perception of chest pain is discussed. PMID- 2910685 TI - Sjogren's syndrome. Its contribution to neuropsychiatric syndrome in patients with primary biliary cirrhosis. AB - The neuropsychiatric status of patients with primary biliary cirrhosis (PBC) was contrasted to that of patients with PBC and accompanying Sjogren's syndrome and to a matched group of normal controls. The subjects with PBC + Sjogren's syndrome had a more profound impairment on a battery of psychometric tests than did the subjects with PBC alone. In addition, they more frequently met the criteria for a psychiatric diagnosis of anxiety disorder than did those with PBC alone. PMID- 2910686 TI - Mentors, masters, and excellence in practice. PMID- 2910687 TI - Understanding the management process and financial and managerial accounting. Part III. Managerial accounting: financial ratio analysis. PMID- 2910688 TI - Implantable insulin infusion pumps: a case presentation. AB - A case is presented of a young woman implanted with a programmable implantable medication system (PIMS). Implanted insulin pumps have been the subject of research for over a decade but have encountered a series of obstacles ranging from design problems to insulin aggregation to catheter blocking from omental tissue. Many of these problems, but not all, have been overcome. Implanted insulin pumps are still in a developmental phase. Glucose sensing is not yet available. Nevertheless, PIMS has demonstrated in this case that it can safely and effectively control insulin-dependent diabetes for over 1.5 years. PMID- 2910689 TI - Experiences with diabetes mellitus and implantable insulin pump therapy: a summary of interview data. AB - A semistructured interview was used to elicit information from 23 implantable insulin pump recipients regarding their concerns about having diabetes mellitus, their decision to receive an implantable insulin pump, and their experiences with the pump. Findings indicated that subjects had present and future concerns about having diabetes mellitus and that they wanted an implantable insulin pump primarily to achieve better control of their diabetes. Subjects said their health generally improved after pump implantation and that the pump had minimal interference with their social lives. Although 16 subjects identified concerns about the pump, all subjects said they would decide again for pump implantation. PMID- 2910690 TI - Self-monitoring of blood glucose by adolescents with diabetes: technical skills and utilization of data. AB - Two studies of adolescent patients were conducted to determine their technical skills and utilization of data obtained by self-monitoring of blood glucose (SMBG). In Study 1, direct observations of 58 adolescents revealed an overall SMBG technical accuracy score of 82%. Most frequent errors were not cleaning fingers (45%), not placing blood on strips correctly (21%), and wiping strip at wrong time (14%). Technical performance was inversely correlated with blood glucose concentration, but was unrelated to other variables. In Study 2, a questionnaire was used to determine SMBG practices among 64 adolescents. Although the majority of patients reported doing daily SMBG, most did not record results in logbooks every time or utilize such data for self-management. No significant relationships were found between SMBG behaviors and other variables. We conclude that periodic evaluation and retraining are required for maintenance of SMBG skills and that methods to enhance utilization of SMBG data be developed for this patient population. PMID- 2910691 TI - The use of goal setting by physicians in the treatment of diabetes. AB - Although physicians commonly report that they use goals in introducing diabetic regimens, little is known about exactly which aspects of established goal-setting techniques are used. This exploratory study sought to ascertain if and how medical doctors employ goal setting in presenting regimens to their patients. Six physicians (second-year metabolism fellows or endocrinologists) were asked to describe their treatment of a "typical" diabetic patient. The responses were analyzed for use of the elements of systematic goal setting. The results indicated that while the physicians had target outcomes in mind they made little use of the key elements of established goal-setting techniques. PMID- 2910692 TI - The art and science of successful teaching (continuing education credit). AB - Many health care professionals don't teach because they were never taught how to organize and present teaching material. To do this effectively requires knowledge of how to assess learner needs, develop a teaching plan, conduct a class, and evaluate both learner progress and program effectiveness. Equally as important are the interpersonal skills, attitudes, and techniques used by the teacher to capture student interest and facilitate learning. This paper describes both the art and science of teaching effectiveness to help the health care provider who was not born a good teacher to become one. PMID- 2910693 TI - The Diabetes Research & Education Foundation: an accessible resource for diabetes educators. PMID- 2910694 TI - A diabetes nurse educator's view of the hospital and burnout. PMID- 2910695 TI - [Cor triatriatum in adulthood]. AB - Cor triatriatum was diagnosed in a 32-year-old woman (Case 1) and a 36-year-old man (Case 2). The definitive diagnosis in Case 1 was made by transthoracic 2-D echocardiography, in Case 2 (after a chance finding) only after additional transoesophageal echocardiography. Colour Doppler echo in Case 1 provided information on the number and localization of membrane openings, while in Case 2 simultaneous measurement of maximal flow velocity and normal right-sided pressures indicated that the anomaly was haemodynamically insignificant owing to the size of the central opening in the membrane (maximal diameter 2.1 cm). In Case 1, abnormal haemodynamic findings on right-heart catheterization provided the indication for surgery and the membrane was successfully removed. Postoperatively the patient was much improved and cardiac catheterization demonstrated normal values. PMID- 2910696 TI - [Granulomatous colitis with pseudopolyp in schistosomiasis]. AB - A 26-year-old Arab had epigastric pain and bloody mucous stools. At coloscopy distal proctitis and a polyp at the rectosigmoid junction were discovered. The polyp had granulomatous inflammatory changes and eggs of Schistosoma mansoni with a characteristic egg shell, central miracidium and lateral spine. Bilharziasis should be considered in the differential diagnosis of chronic inflammatory disease of the intestines. PMID- 2910697 TI - [Nosebleed as the first indication of the HELLP syndrome]. PMID- 2910698 TI - [Anaphylactic reaction to volume substitute agents]. PMID- 2910700 TI - [Retard morphine in the long-term therapy of severe tumor pain]. AB - 35 patients with severe cancer pain received oral retard morphine. Pain reduction was achieved in each case; duration of effectiveness was between 8 and 12 hours. Mean daily dose was 230 mg morphine, but in individual cases the maximal daily dose had to be over 800 mg. The Karnofsky index of physical capacity was increased in all patients. The main side effect was constipation, which actually increased in the course of treatment. On the other hand, nausea and vomiting decreased after a few weeks. No dependence developed in any of the patients. This form of morphine medication thus was effective over long periods and it has become an important part in the range of strongly effective analgesics. PMID- 2910699 TI - [Elimination of aluminum via continuous ambulatory peritoneal dialysis]. AB - Aluminum concentrations in the dialysate and serum of 14 patients on CAPD were measured every six months. Additionally, in ten of the patients Al elimination was measured after a bolus ingestion of 1800 mg aluminium-chloride-hydroxide complex. There was no significant difference between serum Al concentrations initially (47.3 +/- 8.2 micrograms/l), at six months (55.4 +/- 9.5 micrograms/l), and after 12 months (44.3 +/- 10.1 micrograms/l) although the Al concentration in the dialysate had been decreased from 16.6 +/- 2.3 micrograms/l to 1.5 +/- 0.2 in the last six months. The Al concentrations in the effluent dialysate were 14.5 +/ 1.3 micrograms/l initially, 15.6 +/- 1.2 micrograms/l after six months and 11.9 +/- 2.6 micrograms/l after 12 months. During kinetic studies a constant rise of serum Al concentration was found until the fifth hour, from 29.9 +/- 2.5 to 42.5 +/- 4.0, and a decline after 24 hours to 32.4 +/- 3.0 micrograms/l. The quantity of Al eliminated was 41.1 +/- 8.7 micrograms/24 h, equivalent to 1.2% of the ingested dose. In patients with residual renal function, renal Al clearance was almost double the peritoneal one. These results indicate that Al elimination by CAPD is not efficient and ingestion of Al-containing phosphate binders can result in Al accumulation. PMID- 2910701 TI - [Para-aortic pseudoaneurysm following aortic valve replacement. Its diagnosis by magnetic resonance tomography]. AB - Para-aortic pseudoaneurysms after prosthetic replacement of an aortic valve was diagnosed by magnetic resonance imaging (MRI) in two patients and confirmed at surgery. The abscesses had not been visualized in either case by computed tomography and echocardiography, but in one it had been demonstrated by angiography. MRI can thus precisely define site and extent of a para-aortic pseudoaneurysm after aortic valve replacement without any interference by artefact, noninvasively and without use of contrast media. PMID- 2910702 TI - [New principles of pharmacotherapy. The 1988 Nobel Prize for Medicine]. PMID- 2910703 TI - Induction of chromosomal aberrations by hypotonic culture conditions is independent of the S-phase in V79 hamster cells. AB - A deviation from physiological osmolality (300 mOsm/kg H2O) can lead to genotoxic effects. A 30-min treatment of V79 hamster cells with hypotonic sodium chloride of 60 mOsm/kg H2O or with diluted culture medium of the same osmolality induces extraordinarily high frequencies of chromosomal aberrations. In this study, multiple fixation times over a 24-hr period were used to identify cells in various stages of the cell cycle at the time of treatment and to find out whether or not hypotonic conditions are able to induce aberrations in all cell cycle stages. Because of the aberration pattern observed, it is suggested that hypotonic treatment acts as an S-independent agent, like X-rays or restriction endonucleases. Whether the aberrations originate from directly induced DNA damage or from a release of DNase after lysosomal breakdown is discussed. PMID- 2910704 TI - DNA strand breakage in normal and solar ultraviolet-sensitive ICR 2A frog cell lines exposed to solar ultraviolet wavelengths. AB - ICR 2A frog cells and two solar ultraviolet (UV)-sensitive cell lines, DRP 36 and DRP 153, were irradiated with 150 kJ/m2 of the UV radiation produced by a fluorescent sun lamp, the radiation from which was passed through a sheet of 48A Mylar (DuPont, Wilmington, DE) to eliminate wavelengths shorter than approximately 315 nm. The irradiated cultures were also exposed to photoreactivating light (PRL), resulting in the removal of most of the pyrimidine dimers induced by the sun lamp UV irradiation, and then incubated 0-4 hr. At the end of the incubations, the cells were subjected to the alkaline elution assay. In these elutions, the cell lysates were either treated with proteinase K (proK) to eliminate any DNA-protein crosslinks (DPC) that may be present in the cells, or left untreated with proK. For the ICR 2A cells, the level of apparent DNA single-strand breaks (ssb) detected in elutions using proK increased with the incubation time after irradiation and remained high. However, when the DNA was eluted without proK pretreatment, the number of ssb fell rapidly. In contrast, the levels of ssb decreased in the DRP 36 and DRP 153 cells regardless of the use of proK in the elutions. Hence, this differential response in ssb induction may be indicative of a system involved with recovery following irradiation with solar UV wavelengths. PMID- 2910705 TI - Prediction of outcome in human in vitro fertilization based on follicular and stimulation response variables. AB - Since in vitro fertilization (IVF) pregnancy rates have reached a plateau in recent years, there is need for a system of assessment, which could provide a guide for improvements. The follicular characteristics, the response to stimulation, the quality of sperm used for insemination, and the embryonic human chorionic gonadotropin production of 222 women who had undergone routine IVF treatment have been analyzed. Models, predictive of IVF outcome, have been developed using these parameters in various combinations. The results have shown that follicular health and maturity are critical to IVF outcome and that certain patterns of response to ovarian stimulation are associated with the more frequent occurrence of oocytes capable of normal embryonic development after fertilization. PMID- 2910706 TI - Effects of the severity of tubo-ovarian disease and previous tubal surgery on the results of in vitro fertilization and embryo transfer. AB - The purpose of this study was to evaluate the ovarian response and in vitro fertilization/embryo transfer (IVF-ET) results in patients with tubal infertility and two ovaries, according to (1) the degree and extent of pelvic disease (isolated tubal or tubo-ovarian) and (2) previous adnexal surgical procedures. A total of 549 patients who underwent 1031 IVF-ET cycles were evaluated. Significant findings were as follows: (1) No differences were found in the number of preovulatory oocytes, fertilization rates, or serum estradiol levels in the follicular phase between any classes of tubo-ovarian disease. (2) Patients with a "frozen pelvis" had significantly fewer follicles aspirated than those in any other category, although they had equivalent numbers of preovulatory oocytes retrieved and pregnancy rates. (3) Patients with previous bilateral tubal ligation had higher pregnancy rates than patients with severe tubo-ovarian disease. (4) The type of prior pelvic surgical procedure had no effect on IVF-ET outcome. Although patients with no cause of infertility other than tubal ligation had better results, these patients had previously proven fertility. We conclude that neither the stage of tubo-ovarian disease nor any history of pelvic adhesions or tubal surgery has a significant impact on the efficiency of IVF-ET. PMID- 2910707 TI - In vitro fertilization/embryo transfer in the United States: 1987 results from the National IVF-ET Registry. AB - This is the second annual report of the U.S. Registry of IVF-ET and related practices. The present report describes the 1987 experiences of 96 U.S. member clinics with respect to treatments and outcomes. During 1987, 14,647 in vitro fertilization (IVF) and/or gamete intrafallopian transfer (GIFT) stimulation cycles were performed; there were 490 frozen embryo and 60 donor oocyte transfers. Ninety percent of the clinics had at least one delivery, and overall, a total of 1858 babies were born. The overall clinical pregnancy rates were 16% for IVF (based on 8725 retrievals), 25% for GIFT (based on 1968 retrievals), and 28% for IVF and GIFT in combination (based on 199 retrievals). The results for each procedure are described in detail. PMID- 2910708 TI - Evaluation of high vaginal insemination at oocyte recovery in patients undergoing in vitro fertilization. AB - The value of high vaginal insemination at the time of oocyte recovery for in vitro fertilization (IVF) has been assessed. A previous study reported a dramatic increase in the incidence of pregnancy in women after high vaginal insemination (53%) compared with those without insemination (23%). Of 306 patients undergoing IVF, 97 (32%) became pregnant and 20 (21%) miscarried. Those patients with tubal damage numbered 187. Sixty (33%) became pregnant and 10 (17%) miscarried. The data were assessed according to the numbers of conceptuses replaced, the age of the patient, and whether a spontaneous luteinzing hormone surge or human chorionic gonadotropin was a trigger for ovulation, each with a significant effect on the outcome of treatment. No significant effect of the use of high vaginal insemination was found. PMID- 2910709 TI - Partial zona dissection of the human oocyte: a nontraumatic method using micromanipulation to assist zona pellucida penetration. AB - Partial zona dissection (PZD), a method using mechanical force to open the human zona pellucida, and zona drilling, which uses acidic Tyrode's (AT) medium, were compared in 1-day-old oocytes prior to reinsemination. The incidences of monospermy and polyspermy were 13/54 (24%) and 14/54 (26%) following PZD and 6/46 (13%) and 8/46 (17%) following the use of AT medium. This compared favorably with conventional reinsemination: 15/161 (9%) monospermy and 4/161 (3%) polyspermy. Three of the 27 PZD embryos became blastocysts, while none of the AT-exposed embryos developed satisfactorily. Eleven male-factor couples had some of their oocytes randomly treated with PZD prior to insemination; each of the patients had non-micromanipulated control oocytes. Monospermic fertilization and cleavage (23/34; 68%) doubled (P less than 0.05) when PZD was compared with the control oocytes (10/30; 33%). Replacing two PZD and a single control embryo in two patients resulted in twin pregnancies. A third twin pregnancy was established following replacement of only micromanipulated embryos. PMID- 2910710 TI - Effect of indomethacin on the vascular architecture of preovulatory ovine follicles: possible implication in the luteinized unruptured follicle syndrome. AB - Ovarian follicles sometimes fail to rupture and accumulate large quantities of fluid, yet undergo luteinization and form a steroidogenically competent luteal structure, the luteinized unruptured follicle syndrome. This condition can be mimicked in mammals by administration of indomethacin, an inhibitor of biosynthesis of prostaglandins. Blockade of ovulation by this drug is exerted at the follicular level. Ovulatory failure in sheep given a single intramuscular injection of indomethacin after induction of a surge of of luteinizing hormone was associated with follicular hyperemia as assessed by scanning electron microscopic examination of microcorrosion vascular casts and light microscopic quantification of follicular vascular space. The apical stigma of control (ovulatory) follicles was ischemic. The luteinized unruptured follicle syndrome appears to be the consequence of a chronic follicular inflammatory-like reaction involving inhibition of synthesis of prostaglandins. PMID- 2910711 TI - Determining proportions of human X and Y sperm with a recombinant deoxyribonucleic acid probe carrying a homologous sequence of sex chromosomes. AB - A molecular sexing assay method for human sperm DNA has been described, which is particularly suitable for estimating proportions of X and Y sperm in a large number of sample points. The method should have general applicability for testing any mammalian sperm species, since it is based on probing the homologous DNA sequences that are known to be present probably in all mammalian sex chromosomes. PMID- 2910712 TI - Clinical improvements of specific seminal deficiencies via intercourse with a seminal collection device versus masturbation. AB - In the present study of 50 patients, it was determined that those with seminal deficiencies in masturbated samples showed greater improvement in semen parameters with I-SCD use than the nondeficient groups with which they were compared. The use of I-SCD in oligospermia and OTA Syndrome is therefore indicated, both diagnostically and therapeutically. The subjective rating of sexual stimulation elicited when I-SCD was used was far superior than with masturbation. It is believed the success of I-SCD is due, in part, to this greater degree of sexual stimulation, presumably by added loading of the vas deferens prior to ejaculation. PMID- 2910713 TI - Etiology of miscarriage in polycystic ovary syndrome. PMID- 2910714 TI - Effectiveness of varicocelectomy. PMID- 2910715 TI - Pelvic disease classifications. PMID- 2910716 TI - Gender preselection. PMID- 2910717 TI - Oral clomiphene citrate and vaginal progesterone suppositories in the treatment of luteal phase dysfunction: a comparative study. AB - Oral clomiphene citrate (CC) and vaginal progesterone suppositories (PS) are common treatment modalities in luteal phase dysfunction (LPD). Little is known regarding the relative efficacy of these agents. To study the use of CC and PS in the management of LPD, a retrospective cohort study of patients presenting with infertility was undertaken. Sixty-five patients in whom LPD was diagnosed and corrected, as judged by endometrial biopsies, were studied; 35 were treated with PS and 30 with CC. Using Student's t-tests and chi-square analyses, the two treatment groups were demographically comparable. Using life-table analysis, no one therapeutic approach proved superior. Clomiphene citrate and PS are comparable treatment modalities in the setting of LPD given correction of endometrial lag. PMID- 2910718 TI - Serum CA-125 in women with endometriosis and chronic pelvic pain. AB - Since serum CA-125 concentrations are increased in women with endometriosis, the authors evaluated CA-125 levels to determine whether this serum test would be useful in differentiating between pelvic pain due to endometriosis and other causes. During a 30-month period, 163 women who had had pelvic pain for at least 3 months had a CA-125 level obtained prior to surgery. Serum CA-125 was measured by an immunoradiometric assay. Of the 82 women with endometriosis, 66 (80%) had CA-125 concentrations greater than or equal to 16 U/ml (95% upper limit). The frequencies of elevated levels in minimal, mild, moderate, and severe endometriosis were 52, 86, 100, and 100%, respectively. Of the 81 women without endometriosis, 5 (6%) had elevated concentrations. With the use of serum CA-125 determinations for the detection of endometriosis, the sensitivity was 80%, the specificity was 94%, and the accuracy was 93% when the prevalence of endometriosis was 50%. The authors conclude that determination of CA-125 levels may assist in the evaluation and treatment of women with chronic pelvic pain. PMID- 2910719 TI - Synthesis and secretion of proteins by postpartum human oviductal tissue in culture. AB - An explant culture system that used labelled leucine and two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) with fluorography was used to identify specific de novo synthesized and released polypeptides by the human postpartum oviduct. Both ampulla and isthmus tissue in culture exhibited de novo synthesis and release of a large number of polypeptide subunits. Immunoglobulins A and G appear to be the major proteins produced in the ampulla. In addition, two complexes of acidic (pI less than 5) polypeptide subunits are found primarily in ampulla culture medium. Two families of proteins (Mr 51,000 and 60,000) are released by the isthmus but appear to be minor in the ampulla cultures. PMID- 2910720 TI - Human oviductal fluid proteins. III. Identification and partial purification. AB - The role of the macromolecular constituents of human oviductal fluid (hOF) in reproductive physiology is poorly understood. Oviductal fluid contains proteins derived by transudation from serum and those synthesized and secreted by the tubal mucosa. In this communication, we describe purification of hOF-specific proteins. As a first step, serum proteins were removed with an immunoaffinity gel. Fractionation of the proteins unique to hOF was accomplished with DEAE cellulose chromatography. One of these proteins was obtained in a highly purified state after gel filtration on G-75 Sephadex. This protein of 54 kDa molecular weight had a pI of 4.5 and contained carbohydrate. We propose that this hOF glycoprotein be designated "human oviductin I" (hOV I). PMID- 2910721 TI - Proud to be a nurse. PMID- 2910722 TI - Managing home and career. PMID- 2910723 TI - Should nurses carry malpractice insurance? PMID- 2910725 TI - Management can gain ideas by "walking around". PMID- 2910724 TI - The expanding and contracting role of the LPN. PMID- 2910726 TI - Management--supporting staff to foster patient care. How to use staff empowerment. PMID- 2910727 TI - Management--supporting staff to foster patient care. Impromtu speech inspires congeniality. Interview by Adella V Beil. PMID- 2910728 TI - Management--supporting staff to foster patient care. Solution to collaboration mandate: university and hospital form partnership. PMID- 2910729 TI - Management--supporting staff to foster patient care. Time management--key to survival. PMID- 2910730 TI - Management--supporting staff to foster patient care. Center for the promotion of nursing sets goals. PMID- 2910731 TI - Management--supporting staff to patient care. Solving staffing problems: a twelve hour success story. PMID- 2910732 TI - Geriatric dentistry. PMID- 2910733 TI - Health needs of the elderly. AB - As the percentage of older persons in the American population increases--as it steadily will over the next several generations--health care and related financing programs must adapt accordingly. Priorities must be refocused away from hospital-based acute treatment and more toward home- and community-based care for chronic illnesses, long-term diseases, and disabilities. Also, prevention and holistic treatment must augment the more traditional illness orientation of contemporary American health care. PMID- 2910734 TI - Enhancing the dental office environment for the elderly. AB - Today, health care is the nation's third largest industry. One of the fastest growing segments of this market is the delivery of office-based health services to keep our elderly at home, preventing unnecessary institutionalization. Oral health care and regular dental monitoring are important factors for maintaining the older person in the community. An office staff and physical plant supportive to the needs of older persons will encourage this growing population to maintain consistent contact with the dental practitioner. PMID- 2910735 TI - Rational pharmacotherapy for the elderly. AB - Aging is accompanied by normal physiologic changes. Paralleling these changes, disease further contributes to a decline in optimal organ-system function. Many of these changes produce significant alterations in pharmacodynamics and pharmacokinetics that are relevant to safe and effective pharmacotherapy in the elderly. As aging is accompanied by disease, chronic disease states lead to polypharmacy and drug-drug interactions. Drug therapy may cause further decline in organ-system functions, precipitate or exacerbate preexisting disease, and produce drug-induced illness. Consequently, pharamcotherapy in the elderly should only be instituted following comprehensive dentomedical assessment. Use as few drugs as possible. Prescribe the lowest therapeutic dose. Assess the patient's response frequently for compliance, drug effects, and toxicity. Discontinue unnecessary medications. PMID- 2910736 TI - Oral manifestations of drug therapies in the geriatric patient. AB - Oral manifestations of drug therapies in the geriatric patient must be considered in a multifactorial approach. A logical pattern of individual "normality" must be perceived, and variation from this pattern, with the aid of both physical examination and adequate drug history, will enable the clinician to interpret protean manifestations of untoward actions of chemotherapeutic agents in and about the oral cavity. PMID- 2910737 TI - Heterogeneity of pH in the aqueous cytoplasm of renal proximal tubule cells. AB - Heterogeneity of cytosolic pH was studied with compounds that distribute between the cytosol and mitochondrial matrix in fundamentally different ways, i.e., according to the extent of ionization or according to the function of H+-coupled transport systems. Results show that the average cytosolic pH is considerably more alkaline than the region to which mitochondria are exposed. Because mitochondria are localized predominantly in the basal region, the results are consistent with a transcellular pH gradient within the cytosol of proximal tubule cells. Experiments analyzing the effects of inhibiting efflux of HCO3- at the basal surface and Na+-H+ exchange at the apical surface support the interpretation that the function of these systems contributes to the transcellular pH gradient. The existence of a heterogeneity in pH within the cytosol has important implications concerning the function and regulation of numerous cell processes. PMID- 2910738 TI - Cytosolic-free Ca2+ and cell killing in hepatoma 1c1c7 cells exposed to chemical anoxia. AB - Exposure of cultured hepatoma 1c1c7 cells to KCN and iodoacetate, to produce chemical anoxia, caused a rapid and sustained increase in cytosolic-free Ca2+ concentration, which was associated with depletion of intracellular ATP and glutathione. These changes occurred before the loss of cell viability and were accompanied by the appearance of plasma membrane blebs. Pretreatment of the cells with the Ca2+ chelators Quin 2 or BAPTA markedly delayed both the onset of blebbing and loss of cell viability, but did not affect KCN- and iodoacetate induced loss of ATP and glutathione. Together, these results strongly suggest that a sustained increase in cytosolic Ca2+ concentration plays an important role in killing of hepatoma cells by chemical anoxia. PMID- 2910739 TI - Occurrence of platelet-activating factor (PAF) in normal rat stomach and alteration of PAF level by water immersion stress. AB - We detected platelet-activating substance in gastrointestinal areas, which was confirmed to be platelet-activating factor (PAF) on the basis of the following findings: 1) it comigrated with authentic PAF on thin-layer chromatography; 2) it did not aggregate PAF-desensitized platelets; and 3) its activity was completely antagonized by the receptor antagonists CV3988 and L-652,731. The level of PAF was determined with a bioassay method based on the release of [3H]serotonin from washed rabbit platelets. In the normal rat stomach, the level of PAF was high in the antrum (940 +/- 200 nmol PAF/mol phosphorus of original phospholipids), especially in the antral mucosa (1801 +/- 426 nmol/mol phosphorus of original phospholipids). The stomach PAF level was significantly altered by water immersion stress. Stress for a period of 1 h was associated with a decrease in the antral PAF level to 39 +/- 7% of that of untreated controls. This low PAF level persisted during stress. On the other hand, in the corpus, stress for periods of 1 and 3 h was associated with decreases in the PAF content, and further stress (7 h) resulted in restoration of the PAF level to normal. Furthermore, 7 h of stress was associated with distinct hemorrhagic lesions, which were prevented by CV3988 infused i.v. before the stress. This is the first report of an association between a decrease of the endogenous PAF level in animal tissues and tissue damage. PMID- 2910740 TI - This is FASEB. PMID- 2910741 TI - Radiographic and manometric correlation in achalasia with apparent relaxation of the lower esophageal sphincter. AB - We compared the clinical, radiographic, and manometric findings in 10 patients with atypical achalasia showing complete lower esophageal sphincter (LES) relaxation to 39 patients with classic achalasia (i.e., incomplete LES relaxation). Those with atypical achalasia were younger (46.1 vs 60.6 years), had dysphagia of shorter duration (18.7 vs 45.7 mos), had lost less weight (8.2 vs 21.5 lbs), and had less esophageal dilatation (2.8 vs 3.9 cm). However, the mean LES pressures (34.5 vs 37.7 mmHg) and the esophagogastric junction calibers (4.5 vs 4.8 mm) were similar. Radionuclide esophageal emptying studies were done in 15 patients (6 with atypical achalasia; 9 with classic achalasia) and were abnormal in all. Most patients in both groups (90 and 92%) responded well to pneumatic dilatation. We conclude that achalasia with apparent LES relaxation may represent an early form of this motor disorder and that the radiographic findings remain characteristic except for less dilatation of the esophagus. PMID- 2910742 TI - Enteroclysis in the diagnosis of intestinal obstruction in the early postoperative period. AB - Intestinal obstruction in the early post-operative period may be difficult to diagnose clinically and on plain abdominal radiographs with failure to distinguish obstruction from ileus. During the last 11 years we have examined 14 patients with the enteroclysis technique (small bowel barium enema) for suspected early postoperative small intestinal obstruction. Evidence of obstruction was demonstrated in all cases, the site of obstruction was clearly shown in most patients, and the cause identified in 5. PMID- 2910743 TI - Grey Turner's sign and Cullen's sign in acute pancreatitis. AB - Four patients with acute pancreatitis presenting with Grey Turner's sign or Cullen's sign have been studied by computed tomography (CT). These observations help confirm the precise anatomic pathways by which the extravasated pancreatic enzymes and their effects lead to these cutaneous discolorations. Grey Turner's sign is produced by spread from the anterior pararenal space to between the two leaves of the posterior renal fascia and subsequently to the lateral edge of the quadratus lumborum muscle. Communication may be established to the posterior pararenal space and to the structures of the flank wall. The lumbar triangle, a site of anatomic weakness on the flank wall, may serve as a structural predisposition. Cullen's sign can be seen to be secondary to the tracking of liberated pancreatic enzymes to the anterior abdominal wall from the inflamed gastrohepatic ligament and across the falciform ligament. Another more direct pathway may be extension from inflammatory changes of the small mesentery or greater omentum to the round ligament, and then to properitoneal fat deep to the umbilicus. PMID- 2910744 TI - Computed tomography of retained abdominal sponges and towels. AB - The diagnosis of retained sponges and towels a year or more after surgery is often very difficult. We describe the computed tomographic (CT) findings in 4 patients with this complication; 2 cases of retained sponges and 2 cases of retained towels. While the CT appearance of the retained sponges was not specific, the particular appearance of the retained towels had not been previously described. This appearance is characteristic enough to suggest the correct diagnosis before reoperation. PMID- 2910745 TI - Liver function tests in patients with computed tomography demonstrated hepatic metastases. AB - One hundred patients with computed tomographic (CT) evidence of liver metastases (and confirmation by biopsy or progression of disease) had serum levels of alkaline phosphatase, serum glutamic oxaloacetic transaminase, and serum glutamic pyruvic transaminase measured within two weeks of scanning. All three enzymes were within the normal range in 33% of patients. Even with advanced involvement (defined as three or more metastatic lesions over 3 cm in diameter), 20% of patients had normal levels of all three liver enzymes. Although liver function tests (LFTs) (enzyme levels) are inexpensive and simple to perform, they failed to detect a significant number of patients with liver metastases. PMID- 2910746 TI - Magnetic resonance imaging in hemochromatosis: extrahepatic iron deposition. AB - The magnetic resonance (MR) appearance of the liver in hemochromatosis has been previously described. We report a case in which iron deposition in the pancreas, spleen, and lymph nodes is demonstrated by MR. PMID- 2910748 TI - Clinical use of a nonferromagnetic needle for magnetic resonance-guided biopsy. AB - Five patients who had liver lesions detected by magnetic resonance (MR) and/or computed tomography (CT) were biopsied using MR guidance with a specially designed nonferromagnetic needle. The 20-gauge needle was constructed from Type 316 stainless steel in order to maximize needle visibility and minimize needle tip artifact. In all cases adequate tissue was obtained for diagnosis and no side effects were observed during the biopsy or on clinical follow-up despite the fact that the needle was within the patient in MR for an average of 30 min. PMID- 2910747 TI - Esophageal carcinoma multiplex with gastric metastasis. AB - We describe here the radiographic findings in a patient with multiple synchronous squamous carcinomas of the esophagus with a large metastasis to the gastric cardia. Radiographic documentation of this constellation of tumor involvement has not previously been reported. The mechanisms of esophageal metastasis are reviewed. PMID- 2910749 TI - Computed tomographic evaluation and staging of cecal carcinoma. AB - The preoperative computed tomographic (CT) scans of 14 patients with biopsy proven primary adenocarcinoma of the cecum were reviewed to assess clinical presentation, CT findings, and value of staging by CT. The correlation of CT evidence for tumor invasion beyond the bowel wall with histopathology had predictive value of negative examination of 33% with sensitivity of 78%. More importantly, the correlation of metastatic nodal involvement by CT had predictive value of negative examination of 22% with sensitivity of only 12%. Of chief concern was the involvement of pericolic and mesenteric nodal chains that were not discernible by CT. Computed tomographic tumor staging was accurate in 57% of cases and upgraded in 43%. This study concludes that, although predictive values of positive CT examination are high, CT tends to underestimate disease extent. PMID- 2910750 TI - The value of double-contrast barium enema in amebic colitis. AB - We report here our findings on the double-contrast barium enema given to 8 patients with amebic colitis and a comparison is made with endoscopic features. A definite diagnosis of amebic colitis was made by fecal examination or by endoscopic biopsy. Radiologic findings included fine marginal serration, aphthoid ulcers, minute barium flecks, marginal defects, loss of haustration, and deformities of the bowel. Aphthoid ulcers and marginal defects are both characteristic of amebic colitis. The double-contrast barium enema is most useful for differentiating amebiasis from other forms of colitis. PMID- 2910751 TI - Pneumatosis coli: is there a relationship with sigmoid colon redundancy? AB - Pneumatosis coli (PC) is a process characterized by gas-filled cysts in the wall of the large intestine. The barium enema examinations of 14 patients with idiopathic PC were assessed: 93% involved the sigmoid colon, and 84% of patients with sigmoid pneumatosis had sigmoid colon redundancy in comparison to 14% of the control population (p less than 0.001). It is proposed that the sigmoid cysts result in redundancy by affecting the mesentery and colon length. This redundancy may account for the increased risk of sigmoid volvulus in this condition. PMID- 2910752 TI - Glucagon-induced small bowel air reflux: degrading effects on double-contrast colon examination. PMID- 2910754 TI - Colonoscopic screening of persons with suspected risk factors for colon cancer: II. Past history of colorectal neoplasms. AB - Colonoscopic screening has been recommended for all persons who have had a colorectal adenoma or carcinoma. Such persons have been assumed to be at increased risk of having additional, asymptomatic colorectal neoplasms, the removal of which would reduce morbidity and mortality from colorectal cancer. In this prospective study, initial colonoscopy was performed on 544 asymptomatic subjects with past histories of colorectal index lesions ranging from small tubular adenomas to invasive cancers. In 402 subjects whose worst index lesion was an adenoma, the prevalence of neoplasms detected at colonoscopy, above the reach of the rigid sigmoidoscope, increased with age, male sex, black race, and the number and size of their index adenomas. In 142 subjects whose worst index lesion was invasive cancer, colonoscopy findings were marginally related to age and white race. A subgroup of 133 subjects whose worst index lesion was a single, small (less than 10 mm) tubular adenoma and who had no first-degree relatives with colorectal cancer had only a 3% prevalence of advanced colonic neoplasms (tubular adenomas greater than or equal to 10 mm in diameter; tubulovillous, villous, or severely dysplastic adenomas; or invasive cancers) found on colonoscopy--no greater than would be expected in the general population. Subgroups of the remaining 411 subjects, who had advanced or multiple index lesions, had prevalences of advanced neoplasms ranging from 8% to 18%. These findings indicate that for persons whose only risk factor is a single small tubular adenoma, current screening guidelines could be modified to recommend techniques less costly and less invasive than colonoscopy. PMID- 2910753 TI - Jejunal interposition. AB - Seventeen cases of jejunal interposition for distal esophageal lesions, primarily achalasia, eventuated in excellent clinical function in almost all patients. These results compare favorably with other reported series of the same procedure. The radiologic appearance of the anastomosis with the few complications that occur, however, have not been emphasized and are presented in this paper. PMID- 2910755 TI - Effects of prepro-vasoactive intestinal polypeptide-derived peptides on net fluid flux in small intestine of anesthetized rats. AB - Intravenous infusion of low doses of vasoactive intestinal polypeptide, peptide histidine valine-42, and peptide histidine methionine (and the rat equivalent, peptide histidine isoleucine) into anesthetized rats caused a reduction in net absorption of fluid from the small intestine. Larger doses caused a net fluid secretion. At the same nominal infusion rates, peptide histidine valine-42 appeared to be the most potent. In terms of plasma concentrations achieved, however, vasoactive intestinal polypeptide was approximately six times more active than the other two human peptides. If confirmed in humans, these results would suggest that peptide histidine methionine and peptide histidine valine may be as important as vasoactive intestinal polypeptide in causing the watery diarrhea seen in the Verner-Morrison syndrome in which plasma levels of all three peptides are raised. PMID- 2910756 TI - Mechanism of ethanol-induced jejunal microvascular and morphologic changes in the dog. AB - To study the mechanism of morphologic and microvascular effects of intraluminal ethanol, we perfused jejunal segments of the dog with 6% (wt/vol) ethanol for 0 (control), 10, 20, 30, 60, and 90 min, and measured the time-dependent changes in (a) the prevalence of villi with epithelial damage (i.e., villi with intact blebs plus those with broken blebs) and those without epithelial damage (undamaged villi), (b) the height of the villus core and the patency of lacteals, (c) jejunal albumin loss, and (d) permeability of microvessels of the villus tip by colloidal carbon vascular labeling. We found that (a) the prevalence of villi with epithelial damage or with intact bleb increased progressively during the first 20 min of ethanol perfusion and then declined gradually; (b) the height of the villus core and the patency of lacteals in the undamaged villi and in those with intact bleb decreased during the first 20 min and then gradually increased; and (c) jejunal albumin loss and the prevalence of villi with carbon labeling increased for the first 30 min, after which the former declined gradually whereas the latter remained at a plateau. These findings suggest that contraction of the villus core and compression of the lymphatics are the primary cause of ethanol induced epithelial damage, which is accentuated by increased microvascular permeability and consequent protein leakage. The mechanism of recovery of most parameters, in spite of continuous ethanol perfusion, remains to be investigated. PMID- 2910757 TI - Correlation of ultrastructural aberrations with dysplasia and flow cytometric abnormalities in Barrett's epithelium. AB - Barrett's esophagus develops as a complication of chronic gastroesophageal reflux and predisposes patients to the development of dysplasia and adenocarcinoma of the esophagus. Because light microscopy of dysplasia in Barrett's esophagus shows diminished or absent mucus, we used transmission electron microscopy to compare cytoplasmic organelles required for mucus production in dysplastic and nondysplastic esophageal columnar epithelium. These observations of the rough endoplasmic reticulum, Golgi apparatus, and secretory granules were correlated with histologic interpretations and flow cytometric measurements of abnormalities of DNA content. Ultrastructural abnormalities included depletion and alteration of organelles required for mucus biosynthesis. These abnormalities often were accompanied by cells with markedly distended rough endoplasmic reticulum and massive accumulation of cytoplasmic glycogen aggregates. All 9 patients who had Barrett's dysplasia with or without early adenocarcinoma had ultrastructural abnormalities, as did 3 of 8 patients whose biopsy histology was indefinite for dysplasia. Abnormalities measured by flow cytometry correlated well with the presence of these ultrastructural aberrations. All 9 patients with Barrett's dysplasia with or without early adenocarcinoma had abnormalities observed by electron microscopy and aneuploidy or increased G2/tetraploid fractions measured by flow cytometry. Two of the 3 patients whose biopsies were indefinite for dysplasia and who had ultrastructural abnormalities also had aneuploidy or increased G2/tetraploid fractions. Neither ultrastructural nor flow cytometric abnormalities were found in the remaining 5 patients whose biopsies were indefinite for dysplasia, in 19 of 22 patients with Barrett's specialized metaplasia, or in any of the 7 patients with gastroesophageal reflux disease without Barrett's specialized metaplasia. Two of the 22 patients with Barrett's specialized metaplasia had distended rough endoplasmic reticulum in rare cells, and one other had an aneuploid cell population. We conclude that neoplastic progression in Barrett's esophagus is associated with abnormalities of cytoplasmic organelles required for mucus production. With few exceptions, these ultrastructural aberrations correspond to the presence of dysplasia or of aneuploidy or increased G2/tetraploid fractions. Electron microscopy and flow cytometery detect abnormalities associated with the development of dysplasia and cancer in Barrett's esophagus that may be biologically significant. PMID- 2910758 TI - Effects of cimetidine on gastric alcohol dehydrogenase activity and blood ethanol levels. AB - Chronic use of cimetidine and alcohol are commonly associated, but studies on their interactions are the subject of controversy. To investigate this question, a small ethanol dose (0.15 g/kg body wt) was randomly administered on 2 consecutive days either orally or intravenously to 6 normal volunteers, before and after 1 wk of oral administration of 400 mg of cimetidine twice daily. Although cimetidine did not change the areas under the curve of blood ethanol concentrations after intravenous administration, those after oral alcohol intake were twice as large with cimetidine than without. Similar effects were reproduced in rats after intravenous administration of cimetidine (50 mg/kg body wt). In vitro, cimetidine was a noncompetitive inhibitor of gastric alcohol dehydrogenase activity at concentrations as low as 0.01 mM, 100-fold lower than those needed to inhibit the hepatic dehydrogenase. These results indicate that gastric alcohol dehydrogenase activity governs, in part, the systemic bioavailability of ethanol. Consequently, systemic effects of alcohol may be exacerbated in patients receiving cimetidine. PMID- 2910759 TI - Delayed healing of acetic acid-induced gastric ulcers in rats by indomethacin. AB - We examined the mechanism by which repeated administration of indomethacin significantly delays the natural healing of experimental gastric ulcers induced in rats. Gastric ulcers were produced 5 days after injecting 20% acetic acid (0.03 ml) into the submucosal layer of the gastric wall of the antral-oxyntic border. The natural healing of the acetic acid-induced ulcers was extensively delayed by administering indomethacin (1 mg/kg) subcutaneously once daily for 2 or 4 wk. Subcutaneous administration of natural prostaglandin E2 (1 or 3 mg/kg) twice daily for 2 and 4 wk, together with indomethacin, significantly prevented the delay of ulcer healing. Prostaglandin E2 (3 mg/kg) administered twice daily for 2 wk also significantly accelerated the natural healing of the ulcers. A single administration of prostaglandin E2 (1 or 3 mg/kg) significantly reduced histamine-stimulated gastric acid secretion for 4 h in acute fistula rats with 1- or 2-wk-old ulcers, treated with or without daily indomethacin (1 mg/kg). Endogenous prostaglandin E2 levels in the gastric mucosa of normal rats were significantly reduced for at least 12 h after a single or repeated administration of indomethacin (1 mg/kg) for 2 or 4 wk. Gastric mucosal prostaglandin E2 levels in rats with ulcers (5 days after acetic acid injection) were also markedly reduced by indomethacin. This reduction significantly reverted toward control levels after administration of exogenous prostaglandin E2 (3 mg/kg). These results suggest that endogenous prostaglandin E2 plays an important role in the healing process of gastric ulcers. PMID- 2910760 TI - Rectosigmoid motility and myoelectric activity in progressive systemic sclerosis. AB - Colon motility and myoelectric slow wave activity were compared in 10 patients with progressive systemic sclerosis and 18 controls. Recordings were made in the rectosigmoid and rectum, 25-30 cm and 10-15 cm from the anal margin, respectively, during two 4-min baselines and in response to stepwise distention of the colon with an air-filled balloon. During baseline, the motility (activity index, defined as cumulated areas of all waves divided by recording time) of the rectosigmoid was similar in patients with progressive systemic sclerosis (0.38 +/ 0.61 in baseline 1, 0.86 +/- 1.33 in baseline 2) and controls (1.15 +/- 2.02 in baseline 1, 0.77 +/- 1.01 in baseline 2). Rectal motility was also similar during baseline in patients with progressive systemic sclerosis (1.43 +/- 2.56 in baseline 1, 1.65 +/- 2.47 in baseline 2) and controls (0.56 +/- 0.80 in baseline 1, 0.62 +/- 0.94 in baseline 2). Patients showed a lower tolerance for balloon distention of the colon (average, 130 vs. 184 ml) and a greater amount of contractile activity than controls after balloon distention (rectosigmoid activity index, 1.05 +/- 1.24 vs. 0.07 +/- 0.14; rectal activity index, 2.75 +/- 3.71 vs. 0.13 +/- 0.31). Maximum tolerable volume of balloon distention was inversely correlated to complaints of diarrhea in patients. Slow wave myoelectric activity did not differentiate patients from controls. These findings suggest that diarrhea, and possibly other gastrointestinal symptoms associated with progressive systemic sclerosis, may be due to decreased compliance of the bowel. PMID- 2910761 TI - Influence of cholecystokinin antagonist on the effects of cholecystokinin and bombesin on azaserine-induced lesions in rat pancreas. AB - Both cholecystokinin and bombesin have been shown to promote pancreatic carcinogenesis in the azaserine-rat model. The present study was undertaken to discriminate between the effects of cholecystokinin and bombesin and to establish the modulating properties of the specific cholecystokinin receptor antagonist CR 1409 on pancreatic carcinogenesis. After initiation with 30 mg/kg of azaserine, six groups of 15 Wistar rats were treated for 16 wk with cholecystokinin, bombesin, or gelatin (control), some in combination with CR-1409. Doses of cholecystokinin (2.5 micrograms/kg) and bombesin (10 micrograms/kg) were chosen that rendered approximately equal plasma cholecystokinin levels. Both cholecystokinin and bombesin were found to stimulate pancreatic growth, whereas CR-1409 only inhibited the growth-promoting effect of cholecystokinin significantly. Furthermore, both peptides stimulated the development of putative preneoplastic lesions, whereas CR-1409 only inhibited the effect of cholecystokinin significantly. It is concluded that (a) CR-1409 inhibits the promoting effect of cholecystokinin on pancreatic growth and azaserine-induced early pancreatic lesions and (b) the effects of bombesin cannot be fully ascribed to stimulation of the secretion of endogenous cholecystokinin. PMID- 2910762 TI - A dog model for acetaminophen-induced fulminant hepatic failure. AB - The development of a large animal model of fulminant hepatic failure produced with acetaminophen that should be useful in the development and evaluation of potential medical therapies for the important clinical problem of fulminant hepatic failure is described. Acetaminophen in dimethyl sulfoxide (600 mg/ml) given as three subcutaneous injections, with the first dose (750 mg/kg body wt) being given at noon, the second dose (200 mg/kg body wt) being given 9 h later, and the third dose (200 mg/kg body wt) being given 24 h after the initial dose consistently produces fulminant hepatic failure in dogs. The dimethyl sulfoxide vehicle, injected intramuscularly, does not influence either animal survival or hepatic function in control-treated dogs. No deaths occur within the first 36 h. By 72 h after initial drug administration, the mortality is 90%. Histopathological and biochemical investigations demonstrate a high degree of hepatocellular necrosis in nonsurviving animals without appreciable damage to the kidneys, lungs, or heart. The drug schedule and preparation outlined avoids the administration of large volumes of vehicle and results in prolonged high levels of acetaminophen in the blood sufficient to induce severe hepatic injury. Ranitidine (120 mg/kg body wt i.m.) given 30 min before each acetaminophen dose significantly reduces the mortality and hepatic necrosis produced using this model. This model satisfies all criteria established by Miller et al. for the production of a suitable large animal model of fulminant acute hepatic failure. PMID- 2910763 TI - Intestinal malabsorption of vitamin E in primary biliary cirrhosis. AB - We studied intestinal absorption of vitamin E in 26 adults with primary biliary cirrhosis (PBC) and 6 control subjects. Seven (27%) PBC patients were vitamin E deficient based on the ratio of serum vitamin E to serum total lipid concentrations. An oral vitamin E tolerance test was performed in all patients and control subjects using a loading dose of 2000 IU alpha-tocopheryl acetate with measurement of serial serum vitamin E concentrations over 24 h. Vitamin E absorption was expressed as the maximal rise in serum vitamin E above baseline, the area under the oral tolerance test curve, and these two values divided by the fasting total serum lipid concentration. Absorption of vitamin E was significantly impaired in all PBC patients vs. control subjects (p less than 0.01), in vitamin E-deficient vs. vitamin E-sufficient PBC patients (p less than 0.05 to p less than 0.01), and in PBC patients with serum vitamin E levels below 10 micrograms/ml vs. those with serum vitamin E levels above 10 micrograms/ml (p less than 0.01). Vitamin E absorption was inversely related to stage of PBC, serum cholylglycine, total bilirubin, cholesterol, alkaline phosphatase, aspartate aminotransferase, and prothrombin time. Patients with serum vitamin E below 10 micrograms/ml, serum total bilirubin above 3 mg/dl, serum cholylglycine above 600 micrograms/dl, or serum alkaline phosphatase above 1000 IU/L had severe malabsorption of vitamin E and would be at high risk for the development of vitamin E deficiency. Therefore, vitamin E supplementation should be considered not only in patients in whom overt vitamin E deficiency is present, but also in PBC patients meeting these criteria. PMID- 2910764 TI - Functional and structural changes in parotid glands of alcoholic cirrhotic patients. AB - The parotid gland function and structure was studied in 30 patients with biopsy proven alcoholic cirrhosis and in 43 age- and sex-matched alcoholic and nonalcoholic control subjects. Mean simulated parotid saliva flow rate was significantly (p less than 0.05) lower in patients with alcoholic cirrhosis as compared with alcoholic and nonalcoholic control subjects. A similar reduction was observed in mean basal parotid saliva flow rate in patients with alcoholic cirrhosis that reached statistical significance (p less than 0.05) in comparison with nonalcoholic control subjects. In addition, the concentration of sodium, bicarbonate, and total proteins in stimulated parotid saliva was significantly (p less than 0.005) lower in patients with alcoholic cirrhosis as compared with the two groups of control subjects. Sialograms in 6 patients with alcoholic cirrhosis did not reveal any obstructive lesion in the primary parotid duct or its branches. Histology of salivary tissue revealed an increase in the interstromal fatty infiltration, edema, and fibrosis without evidence of inflammatory reaction in 5 patients as compared with the control subjects. These data provide evidence for marked parotid gland dysfunction in patients with alcoholic cirrhosis presumably due to metabolic derangement and altered parotid gland structure. PMID- 2910765 TI - Gas explosion during diathermy gastrotomy. AB - The first report of rupture of the stomach due to diathermy-elicited gas explosion during gastrotomy in a patient with intestinal ischemia resulting in obstruction and jejunal and gastric dilatation is presented. In the obstructed stomach or small bowel, a proliferation of hydrogen- and methane-producing bacteria can occur, leading to the accumulation of these combustible gases in explosive concentrations. In cases of gastrointestinal tract obstruction, the diathermy knife should not be used in entering the gastrointestinal lumen. PMID- 2910766 TI - Ileostomy and ileal carcinoma. PMID- 2910767 TI - Effects of nonsteroidal antiinflammatory drugs on gastric and duodenal mucosa. PMID- 2910768 TI - Dissociation of pepsinogen and acid secretion. PMID- 2910769 TI - Physicians not exempt from 'forced retirement'. PMID- 2910770 TI - Common upper airway disorders in the elderly and their management. AB - The elderly patient may infrequently present with symptoms or signs of disorders of the upper airway. Once a malignancy or other life-threatening illness has been excluded by a thorough history and physical examination, the physician should then consider one of the common upper airway disorders associated with aging. PMID- 2910772 TI - Conversation with ... William R. Hazzard, MD: Is cholesterol worth worrying about?. Interview by Richard L. Peck. PMID- 2910771 TI - Hypothermia and heat stroke: protecting the elderly patient. AB - Temperature regulation disorders in the elderly are both common and life threatening, yet often go unrecognized. Diagnosis and appropriate management depend largely on a clinician's high index of suspicion. Reviewed are the reasons why the elderly are more susceptible to such disorders, important diagnostic clues, restorative treatments and, most important, practical measures to prevent elderly patients from being exposed to the extremes of heat and cold. PMID- 2910773 TI - Radical hysterectomy with pelvic lymph node dissection for treatment of cervical cancer: a clinical review of 954 cases. AB - Nine hundred fifty-four patients, who received a radical hysterectomy and a bilateral pelvic lymphadenectomy, were included in this study which ran from January 1971 to December 1986. The subjects, by in large, ranged in age from 41 to 60. Of these cases, 62.5% were in clinical stage IB, while 26.2% were in stage IIA. Urinary tract fistula formations occurred in 2.4% of the cases and substantially decreased from 6.1% during 1971-1978 to 0.9% in the subsequent period from 1979 to 1986. The operative mortality rate was 0.4%. The follow-up included 438 cases that came from 1971 to 1981, and each was evaluated over a period of 5 years. Of these cases, 28 patients were lost during the follow-up period and were presumed to have died from cancer. The absolute 5-year survival rates for the patients in stage IB, stage IIA, and IIB were 86.1, 71.7, and 60.1%, respectively. The respective 5-year survival rates for patients with stage IB LN(-) and LN(+), i.e., without or with lymph node metastasis, were 87.7 and 73.1%. The survival rates for patients with stage IIA LN(-) and LN(+) were 79.8 and 40.9%, respectively. In retrospect, the 5-year survival rates seem to be related to age, parametrial involvement, and histological type. This study shows that because of improving surgical techniques and anesthesia, acceptable operative morbidity and mortality, as well as favorable 5-year survival rates, radical surgery seems to be the treatment of choice for patients with early invasive uterine cervical, and especially for younger women. PMID- 2910774 TI - Prognostic factors in squamous cell carcinoma of the vulva: a multivariate analysis. AB - Based on 124 patients with squamous cell carcinoma of the vulva treated at the 1. Frauenklinik der Universitat Munchen from 1971 to 1980, the influence of pretreatment characteristics on survival was assessed. The patients underwent a simple vulvectomy with local and inguinal irradiation. All histologic specimens were worked up in the same manner, and all available specimens were reverified. Follow-up lasted from at least 2 up to 12 years post-treatment, with no dropouts. Using the Cox model of multivariate analysis, five pretreatment characteristics were found to most strongly influence survival: age, dissociated tumor growth, lymphatic spread, tumor thickness, and ulceration. These pretreatment characteristics were implemented in an algorithm for survival-oriented prognostic forecasting. Survival data as predicted from this algorithm correlated well with observed survival data. The validity of these prognostic factors needs to be examined in further studies using comparable patient populations and study designs. PMID- 2910776 TI - Endometrial stromal sarcoma: a report of nine cases. AB - Nine cases of endometrial stromal sarcoma are described. Four of the patients were categorized as having a uterine endolymphatic stromal myosis (ESM) with less than 10 mitoses per 10 HPF and five patients as having an endometrial stromal sarcoma (ESS) with more than 10 mitoses per 10 HPF. Another prognostic distinction based on the degree of stromal differentiation is also discussed. The symptomatology, diagnostic means, clinical features, and treatment are described. PMID- 2910775 TI - In vitro sensitivity of ovarian cancer as determined by a short-term biochemical assay: comparison between primary and metastatic sites in the same patient. AB - Tumor sensitivity of ovarian cancer to cytotoxic drugs in vitro was examined between paired samples taken from the primary tumor and its metastases in the same patient. A 3-hour assay of primary cultures of the tumor was used to determine cellular response to the drugs by measurement of the incorporation of [3H]thymidine. Although there was variability, a reasonable correlation was found between the primary tumor and its different metastases, between the different metastases, and between the different tumor sites and cells from the peritoneal fluid. However, there was discordance between some of the pairings; the rate varied between 12 and 42% when the criterion was greater than 20% inhibition. Consistent drug sensitivity for all sites tested was present in only 8 of the 18 patients. Because of the discordance in some pairings, attempts should be made to sample all metastatic tumors, particularly those which cannot be removed completely by surgery. The discordant subgroup may be a source of false-negative and false-positive results of the assay. PMID- 2910777 TI - Characterization of human ovarian and endometrial carcinoma cell lines established on extracellular matrix. AB - Six cell lines were established from four patients with advanced carcinoma of the ovary and from one patient with carcinoma of the endometrium. These lines were established from fresh tumor material maintained initially on culture dishes coated with an extracellular matrix (ECM) produced by bovine corneal endothelial cells. Two of the six lines continue to require ECM as a substrate for optimal growth while the remaining four lines will proliferate on ECM or plastic substrate. Four cell lines transplanted into athymic nude mice were tumorigenic and maintained histologic and karyotypic similarities between the patient's original tumor, the cell line, and the transplantable tumor. Furthermore, in vitro degradation of ECM was grossly apparent by those cell lines which formed nude mice xenografts. Tumor cells were characterized by cytology, transmission electron microscopy, karyology, substrate requirements, steroid binding protein analysis, and morphological appearance in culture. PMID- 2910778 TI - Human breast tumors: a comparison between the biochemical method of measuring estrogen and progesterone receptors and that of an immunohistochemical method. AB - In a series of 94 human mammary carcinomas, the determination of total estrogen (ER) and progesterone (PR) receptors by a single saturating dose method (5 nM for ER, 10 nM for PR) using dextran-coated charcoal was compared to an immunohistochemical method utilizing ER monoclonal antibody (ER-ICA test). There was a good correlation expressed in positive terms between the ER-ICA test and the biochemical determination of ER (94% of concordance) with a statistical value of P less than 0.01 being found between the concentration of ER (biochemical) and the percentage of labeled cells (ER-ICA). The ER-ICA test complements the ER and PR (biochemical) and is particularly useful for ER determinations on small tumor specimens as no additional tissue other than that from the biopsy is required. PMID- 2910779 TI - Comparative study of intravenous and intraarterial cis-platinum on intratumoral platinum concentration in carcinoma of the cervix. AB - In order to define the influence of intraarterial administration of cis-platinum in tumors of the cervix, a preliminary crossover study was performed to measure and compare the intratumoral concentrations (ITC) of platinum obtained respectively after intravenous (iv) and intraarterial (ia) (both bilateral hypogastric arteries) injection. The results in nine patients demonstrate that higher (P = 0.05) intratumoral concentrations are obtained after intraarterial injection of cis-platinum: 10; 3.7-23.7 ng Pt/mg of dry tissue after ia (median; range) 6.9; 4.1-23.6 ng Pt/mg tissue after iv. This difference is probably too small to be of clinical significance and a comparative clinical trial does not seem to be warranted. The results also show a large intersubject variation in intratumoral platinum concentration which are reproducible in patients whatever route of administration is used. Thus the observed differences in ITC are more related to the variability of the tumor properties than to the route of administration. PMID- 2910780 TI - The relationship of steroid receptor expression to nuclear DNA distribution and clinicopathological characteristics in epithelial ovarian tumors. AB - Tumor specimens from 92 patients with ovarian carcinoma were analyzed for estrogen receptor (ER), progesterone receptor (PR), proliferative fraction, and ploidy. Seventy-one percent of tumors were either ER+ (greater than 5 fmole/mg protein) or PR+ (greater than 10 fmole/mg protein) with 27% of tumors overall being both ER+ and PR+. There was no significant relationship between receptor expression and stage, grade, or histological subtype. Thirteen percent of diploid tumors were receptor negative in contrast to 38% of aneuploid tumors (P less than 0.01). There was no significant association between ER status and ploidy, but 60% of diploid tumors were PR+ in contrast to 33% of aneuploid tumors (P less than 0.02). Eleven percent of tumors overall were both ER rich and PR rich and comprised 23% of diploid and 5% of aneuploid tumors (P less than 0.01). Receptor negative tumors had a median S phase of 18.8% which was significantly higher than the median S phase of 12% in receptor-positive tumors (P less than 0.02). A similar analysis was also performed on specimens from 9 patients with borderline epithelial ovarian tumors and 12 with benign epithelial ovarian tumors. Up to 50% of benign and borderline epithelial tumors had measurable receptors, but all were diploid with a relatively low S phase fraction. The functional significance of steroid receptor expression in ovarian cancer is unclear, but the association with ploidy and proliferative activity particularly in patients with malignant ovarian tumors may allow better identification of prognostic subsets and aid in selection of patients for hormonal therapy. PMID- 2910781 TI - Neuron-specific enolase as a serum marker for immature teratoma and dysgerminoma. AB - Neuron-specific enolase (NSE) was measured with an enzyme-immunoassay in sera from 54 patients with malignant (24 cases) and benign (30 cases) germ cell tumors of ovarian origin. Serum NSE contents were clearly raised above control value (greater than 10 ng/mg) in 4 of 8 patients with immature teratomas and 5 of 6 with dysgerminomas. NSE was also measured in nine cell lines of germ cell tumors. Among these cell lines, high NSE contents were detected in the cell extracts and culture supernatants from PA-1 and Tera-II lines. In immunohistochemical study, widespread positive staining for NSE was shown in dysgerminomas, whereas the immunostaining was confined to neural elements in both an immature teratoma and xenograft tumors derived from PA-1 and Tera-II lines in nude mice. These findings suggest that serum NSE measurements are of diagnostic value not only for immature teratomas but also for dysgerminomas. PMID- 2910783 TI - Propensity of retroperitoneal lymph node metastasis in patients with stage I sarcoma of the uterus. AB - Information in the literature about the incidence of nodal spread and its clinical implication in stage I sarcoma of the uterus is limited. The purpose of this study is to provide additional information derived from surgical staging of 20 patients who were treated by primary surgery to include total abdominal hysterectomy, bilateral salpingo-oophorectomy, and selective biopsy of paraaortic and pelvic nodes. Nine out of 20 patients (45%) of this small series had lymph node metastases either to both pelvic and paraaortic nodes (6) or pelvic nodes alone (3). This high rate of nodal involvement was associated with deep myometrial invasion, uteri sounding larger than 8 cm, patients older than 65 years, and leiomyosarcoma. In 12 of 20 patients, clinical staging was an underestimate. In a follow-up from 2 to 12 years, all 9 patients with positive nodes succumbed to their diseases. This result indicates that incidence of nodal spread in stage I sarcoma of the uterus is a frequent occurrence and is related to ultimate survival. Furthermore, it suggests that lymphatic permeation might precede hematogenous spread in early sarcoma of the uterus. PMID- 2910782 TI - A randomized comparison of a rapid versus prolonged (24 hr) infusion of cisplatin in therapy of squamous cell carcinoma of the uterine cervix: a Gynecologic Oncology Group study. AB - In this study, 331 patients with advanced or recurrent squamous cell carcinoma of the cervix no longer amenable to control with surgery or radiotherapy were randomized to receive cisplatin 50 mg/m2 as either a continuous infusion over 24 hr or a more rapid infusion at a rate of 1 mg/min. Antiemetic therapy was standardized for the initial course of both regimens as metoclopramide 60 mg at the time of and at 3 and 6 hours after initiation of cisplatin. The overall frequency of objective regression of disease was 18%; the response rate in each regimen was essentially identical. The continuous infusion regimen was associated with a significantly greater percentage of patients who experienced no nausea and vomiting (34% versus 18%, P = 0.002). Other adverse effects included nephrotoxicity, peripheral neuropathy, myelosuppression, and ototoxicity. Both the frequency and severity of these were essentially the same for each regimen. PMID- 2910784 TI - Malignant struma ovarii. AB - Malignant struma ovarii is a very rare tumor, with considerable disagreement concerning the necessary histologic features for malignancy. The prognosis with patients with a malignant struma ovarii is difficult to make because of inadequate follow-up of the reported cases and long clinical courses. In most cases the patients responded well to surgical treatment but sometimes patients have died from malignant struma ovarii, in particular, if there is metastasis. There is evidence that radioactive iodine is effective in treating metastatic struma. The present case reports the use of intraperitoneal chronic phosphate for metastatic intraperitoneal disease, with thyroid suppression. Long-term follow-up will be necessary to properly evaluate this therapy. Prophylactic administration of thyroid hormone should be considered in cases of malignant struma ovarii. PMID- 2910785 TI - A study of cis-platinum and ifosfamide in alkylating agent-resistant ovarian cancer. AB - Twenty patients with advanced epithelial ovarian carcinoma who had failed alkylating agent treatment were given cisplatin 60 mg/m2 together with ifosfamide 4 g/m2 and mesna 6 g/m2 every 4 weeks for 4-6 cycles. The overall response rate was 45% and the complete response rate 20%. The median time to disease progression was 9 months and 4 of the 9 responding patients are alive at more than 2 years. WHO Grade 3 or 4 myelosuppression was seen in 7 patients, nephrotoxicity in 4, and encephalopathy in 1 patient. Nausea and vomiting of moderate severity (WHO Grade 3) was seen in the majority of patients. While a dose escalation of 25% of both drugs was possible in 4 patients, myelosuppression became limiting at the higher dose. The combination of cisplatin and ifosfamide is effective in relapsed ovarian cancer even in this group of patients with heavy pretreatment. PMID- 2910786 TI - The effect of the alpha-emitting radionuclide lead-212 on human ovarian carcinoma: a potential new form of therapy. AB - To improve response and survival of patients with ovarian carcinoma noncross resistant forms of therapy must be developed. alpha-emitting radionuclides may be therapeutically useful since they can directly ionize with energies of 5 to 9 MeV, penetrate only a few cell diameters, and transfer a high amount of energy. The purpose of this study was to determine the effect of the alpha-emitter, lead 212 (212Pb), complexed to sulfur in a nude athymic mouse model (NIH:OVCAR-3) containing human ascites and solid epithelial ovarian carcinoma. Thirty-six nude mice 28 to 32 days old were injected with 10(7) to 10(8) carcinoma cells from donor mice. After 4 weeks, six groups of six nu/nu athymic BALB-C mice were intraperitoneally injected with 70, 50, 20, 5 microCi of 212Pb sulfur colloid, sulfur colloid, or saline. Tumor necrosis with a decrease in ascites and a dose related survival were noted with doses of 50, 20, and 5 microCi. With 70 microCi acute gastrointestinal toxicity developed. These experiments form the basis for further investigations and the development of alpha-emitting radiocolloids which may be of therapeutic efficacy in the treatment of intraperitoneal ovarian carcinoma. PMID- 2910787 TI - Second-look procedures in ovarian cancer patients receiving six vs. nine courses of platinum, adriamycin, cytoxan (PAC) chemotherapy: the SCPMG experience 1982 1985. AB - From July 1, 1982, through December 31, 1985, 100 patients with Stage I, II, or III ovarian cancer, who were clinically NED following primary chemotherapy, underwent second look laparotomy. A prospective, nonrandomized study was set up among the various institutions within the Southern California Kaiser Permanente Medical Group. Those patients being treated at the Tertiary Oncology center received six courses of PAC while patients treated at other centers received nine courses of PAC. There was no selection as to severity of disease. Patients with Stage IV disease were not subjected to second-look procedures. Twenty patients with Stage I disease received other than PAC chemotherapy. Eighty patients with Stage II and III disease received PAC chemotherapy; 39 had six courses and 41, nine courses or more of PAC. Standard second-look procedure was performed and the status of the second-look procedure was the determining factor of response. Eighteen of the 39 patients (46%) who received six courses and 26 of 41 patients (63%) who received nine courses of chemotherapy had negative second-look procedures. Sixty-five patients had Stage III ovarian cancer, 34 with six courses of therapy and 31 with nine courses of therapy. There was no statistical difference in the incidence of positive or negative second-look procedures between the groups. The therapeutic index of six courses of PAC chemotherapy was in our hands, higher than with nine courses, since there was no observed difference in the status of the second-look and there was significantly more toxicity with the nine courses of therapy. PMID- 2910788 TI - Cervical carcinoma: a comparison of four potential biochemical tumor markers. AB - A longitudinal study of circulating immune complexes (CIC), cancer antigen 125 (CA125), carcinoembryonic antigen (CEA) and a sub-fraction of the TA-4 squamous cell carcinoma tumor-associated antigen (SCC) has been undertaken in 38 patients with cervical carcinoma. Pre- and post-treatment values have been compared with those obtained in well-defined clinical remission and relapse phases of their disease. Each tumor marker was assessed in terms of "lead time" before clinically obvious recurrent disease became evident. The data from the four subjects with adenocarcinoma of the cervix gave equivocal results and no firm conclusions could be drawn. However, for the 34 patients with squamous cell carcinoma the medium value (data was skewed) for SCC was elevated above normal in the presenting pretreatment sera (4.5 ng/ml) and significantly fell to 2.5 ng/ml post-treatment (P less than 0.01). A similar pattern was not apparent for CIC, CEA, or CA125 data. When results were examined for an individual patient, of those with recurrent squamous cell lesions who died, 12/24 demonstrated elevated, and rising SCC values before clinical evidence of the disease and a further 6 (25%) at the time recurrence was clinically evident. This information gave lead times of between 2 and 52 months (median 13 months) for 75% of patients. Only 1 subject had values which remained in the normal range (less than 2 ng/ml) even though their disease was progressive. Similarly of the subjects still in clinical remission 8/9 had values within the normal range. The data for CIC, CA125, and CEA were not individually useful as a marker. Furthermore, combining the data from all analytes to give a panel of potential markers did not improve the prognosis already evident with SCC alone. It has therefore been concluded that SCC is a useful biochemical marker of the progression of squamous cell carcinoma of the cervix. PMID- 2910789 TI - Pulmonary lymphangitic carcinomatosis secondary to cervical carcinoma: a case report. AB - Pulmonary lymphangitic carcinomatosis is a rare form of metastatic cervical cancer. A patient with persistent squamous cell carcinoma of the cervix presented with symptoms suggestive of pulmonary embolism and right heart failure. Pulmonary lymphangitic spread of the cancer was found postmortem. The pathogenesis of pulmonary lymphangitis carcinomatosis is reviewed and diagnostic evaluation discussed. PMID- 2910790 TI - Uterine tumors in ataxia-telangiectasia. AB - Roughly one-third of patients with ataxia-telangiectasia (AT) develop malignant tumors, usually of lymphoid origin. AT patients also exhibit progeric changes. We describe three patients, between the ages of 27 and 32 years, with uterine tumors: one with a frank leiomyosarcoma and chronic T-cell leukemia, one with a multilobulated leiomyoma of uncertain malignant potential, and one with an unremarkable leiomyoma. Thus, the spectrum of tumors in AT patients beyond adolescence includes nonlymphoid malignancies and precocious, benign leiomyomas. PMID- 2910791 TI - Familial 46,XY pure gonadal dysgenesis and gonadoblastoma/dysgerminoma: case report. AB - The case reports of two sisters admitted for evaluation of primary amenorrhea are presented. Gynecological and endocrinological investigations and chromosomal analysis led to the diagnosis of familial 46,XY gonadal dysgenesis. Both sisters underwent bilateral salpingo-oophorectomy and hysterectomy. Histological examination revealed dysgenetic gonads with gonadoblastoma and dysgerminoma. Five years after treatment by surgery and irradiation the patients are well and free of recurrence. These cases again confirm the risk of malignancy and the necessity of prophylactic gonadectomy in all patients with gonadal dysgenesis and Y chromosomal material. PMID- 2910792 TI - Hospital profits flatten to pre-PPS levels. PMID- 2910793 TI - Insurers, HMOs and BC/BS plans talk about AIDS. PMID- 2910794 TI - Maryland quality program eases data pitfalls. PMID- 2910796 TI - Competition brings era of integrated computer systems. PMID- 2910795 TI - Financial systems still lag behind users' needs. PMID- 2910797 TI - Breakthroughs in hospital finance. PMID- 2910798 TI - Psychologists' staff privileges in dispute. PMID- 2910800 TI - CEO recognizes importance of content workforce. PMID- 2910799 TI - 'Center of excellence' name tag carries clout. PMID- 2910801 TI - CEOs cautioned to watch Stark's referral bill. PMID- 2910802 TI - Managed care, indemnity insurance products blur. Interview by Michele Robinson. PMID- 2910803 TI - University PPO bets quality care will cost less. PMID- 2910804 TI - Generic drugs: boon or bust for quality? PMID- 2910805 TI - Employers and insurers to seek preset prices. PMID- 2910806 TI - Limited use for product management in hospitals. PMID- 2910807 TI - Stable rates predicted; trouble spots remain. PMID- 2910808 TI - Info systems critical to 1989 planning, success. PMID- 2910810 TI - Customer perception counts in quality assurance. PMID- 2910809 TI - How to use an executive-recruitment firm. PMID- 2910811 TI - Urinary electrolytes and blood pressure in three Yi farmer populations, China. AB - The relation between blood pressure and urinary electrolytes, including sodium, potassium, calcium, and magnesium were examined in male farmers of the Yi nationality who live in three separate communities in Sichuan and Yunnan provinces in China, where the lifestyles, habits, and living conditions are very different. One of these three communities was unacculturated and had the lowest average blood pressure as well as the lowest prevalence rate of hypertension in China; one was acculturated and had the highest average blood pressure; and the third was moderately acculturated with its average blood pressure between the other two. Blood pressure was taken on each of 3 days and corresponding 24-hour urine specimens were collected to measure potassium, sodium, calcium, magnesium, urea nitrogen, and creatinine. Ecological and individual-based data correlation analyses were employed to study the relations among age, body mass index, some related indexes of electrolyte derivatives, and blood pressure. Multiple regression analyses were used to explore the relation of blood pressure to the above indexes, adjusted for age, body mass index, urea nitrogen and creatinine, and geographical differences. Statistically significant correlation analyses showed that systolic blood pressure was positively associated with sodium creatinine, calcium-creatinine, sodium-potassium, calcium-magnesium, and urea nitrogen and creatinine ratios; negatively associated with potassium-creatinine and magnesium-creatinine ratios. The ridge regression analysis selected only calcium-magnesium ratio as a predictor of systolic blood pressure. PMID- 2910812 TI - A gene for high urinary kallikrein may protect against hypertension in Utah kindreds. AB - The inheritance of 12-hour overnight total urinary kallikrein excretion and its association with family history of essential hypertension were studied in 405 normotensive adults and 391 youths in 57 Utah pedigrees. Total urinary kallikrein excretion was highly familial with 51% of the total variance attributable to a dominant allele for high total urinary kallikrein excretion and 27% attributable to the combined effects of polygenes and shared family environment. An estimated 28% of the population has one or two copies of the dominant allele for high total urinary kallikrein excretion (2.3 SD units higher than the low homozygotes). About 83% of the population could be assigned to one of the two genotypic populations. Individuals with the high total urinary kallikrein excretion genotype were significantly less likely to have one or two hypertensive parents (relative odds = 0.56, p = 0.042). We conclude that a dominant allele expressed as high total urinary kallikrein excretion may be associated with decreased risk of essential hypertension. Further studies should be performed to confirm this finding and to test for interactions between this apparently protective gene and other genetic and environmental determinants of essential hypertension. PMID- 2910813 TI - Comparison of variability of urinary sodium, potassium, and calcium in free living men. AB - The variability of 24-hour urinary sodium, potassium, and calcium excretion was studied in a sample of 22 Neapolitan men with mild blood pressure elevation. On 5 days within a 1-month period, 24-hour urine specimens were collected by each subject. The estimated ratio of intraindividual-to-interindividual variance was 1.12 for urinary sodium, 2.46 for urinary potassium, and 0.52 for urinary calcium. Based on these values, five 24-hour urine collections are necessary to reduce to less than 10% the diminution of the correlation coefficient between urinary sodium and another related variable; this number is substantially lower than that found in previous studies in a North American population sample, but similar to the one reported for Chinese population samples. Ten urinary collections are needed for potassium excretion. A different and more favorable situation is observed for 24-hour calcium excretion, as only two collections are necessary for the adequate characterization of individuals in a population. PMID- 2910814 TI - Thromboxane synthase inhibition enhances action of converting enzyme inhibitors. AB - Mean arterial blood pressure was measured over a 24-hour period from the femoral artery of conscious, unrestrained spontaneously hypertensive rats. Oral administration of the angiotensin converting enzyme inhibitor CGS 16617 significantly lowered mean arterial pressure. In contrast, both the thromboxane synthase inhibitor CGS 12970 and the thromboxane receptor antagonist BM 13505 lacked an antihypertensive action in the spontaneously hypertensive rat. When administered concurrently, the thromboxane synthase inhibitor CGS 12970 potentiated the antihypertensive action of the angiotensin converting enzyme inhibitor CGS 16617. This effect was not observed with the thromboxane receptor antagonist BM 13505. In addition to CGS 16617, CGS 12970 also potentiated the hypotensive effect of two structurally dissimilar angiotensin converting enzyme inhibitors, benazapril HCL and captopril. Indomethacin blocked the thromboxane synthase inhibition-induced potentiation of the antihypertensive action of angiotensin converting enzyme inhibitors. The thromboxane synthase inhibitor CGS 12970 had no effect on the hypotension induced by hydralazine, indicating that the hypotension is not a nonspecific action related to the fall in blood pressure. These results may suggest that converting enzyme inhibition augments the levels and actions of a hormone that stimulates prostaglandin formation. It is well established that thromboxane synthase inhibitors eliminate the formation of the vasoconstrictor thromboxane A2 and allow reorientation of eicosanoid production toward the formation of vasodilating prostaglandins, which could enhance the antihypertensive action of angiotensin converting enzyme inhibitors. PMID- 2910815 TI - Regenerative electrical activity and arterial contraction in hypertensive rats. AB - Isolate tail arteries from spontaneously hypertensive rats-stroke prone strain (SHRSP) display oscillatory contractile responses to norepinephrine. These oscillations are not observed in tail arteries from normotensive Wistar-Kyoto rats (WKY). The mechanism underlying these oscillatory contractions was investigated by simultaneous measurement of isometric force development and membrane potential (Em) from tail artery strips in vitro. After equilibration in physiological salt solution containing 1.6 mM calcium (37 degrees C), resting Em was not different between WKY (-52 +/- 1.1 mV) and SHRSP (-52 +/- 0.4 mV). Norepinephrine (3 x 10(-7) M) produced a similar degree of depolarization in tissues from the two strains (WKY = (-42.5 +/- 0.9, SHRSP = -41 +/- 0.8). However, while Em recordings from WKY arteries were quiescent, those from SHRSP displayed bursts of electrical spiking activity that were temporally associated with the rising phase of oscillations in contractile force. The frequency and duration of these bursts of action potentials increased with the concentration of norepinephrine. Action potentials were not observed in calcium-free solution or in presence of nifedipine (3 x 10(-7) M). Releasing the passive stretch on the tissues caused a decrease in the rate of spiking. These studies demonstrate catecholamine-induced regenerative electrical activity in tail arteries from SHRSP that is dependent on extracellular calcium. This activity is unique to tail arteries from this strain. PMID- 2910816 TI - Systemic and regional hemodynamic effects of dietary calcium supplementation in mineralocorticoid hypertension. AB - This study was undertaken to determine the systemic and regional hemodynamic effects of long-term dietary calcium supplementation in mineralocorticoid (DOC) salt hypertension. Systemic and regional hemodynamic measurements were determined by the radioactive microsphere technique in conscious and unrestrained rats (kidneys intact) with DOC-salt-induced hypertension that were pair-fed either a normal calcium (0.6% by weight, n = 12) or a calcium-supplemented (high-calcium) diet (2.5% by weight, n = 12). After 7 to 8 weeks, there were no differences in weight, heart rate, or cardiac output between the two groups. In contrast, the high-calcium rats had a significantly lower mean blood pressure (125 +/- 4 mm Hg, mean +/- SEM) than the normal calcium rats (143 +/- 5 mm Hg); this finding appeared to result predominantly from a reduction in total peripheral resistance. The high-calcium rats had a higher renal blood flow (7.8 +/- 0.5% vs. 6.2 +/- 0.4% cardiac output; p less than 0.05) and lower renal (14.3 +/- 1 vs. 19.3 +/- 2 mm Hg/min/ml/g tissue; p less than 0.05) and jejunal vascular resistance than did the normal calcium rats. Two additional identical groups of normal calcium-and high-calcium-DOC-salt rats (n = 12 each) were also studied. In these rats, serum ionized calcium decreased significantly (p less than 0.05) from baseline in both groups. Urinary sodium increased in both groups but did not differ significantly. In conclusion, dietary calcium supplementation attenuates the rise in peripheral vascular resistance that accompanies DOC-salt hypertension. This attenuated resistance appears to be relatively selective and is noted particularly in the renal vasculature. PMID- 2910817 TI - [Education at your service]. PMID- 2910818 TI - The right to perform grey area acts. PMID- 2910819 TI - Modifications to the Professional Code. PMID- 2910820 TI - [Homes for the aged in Quebec: not only a matter of enough money]. PMID- 2910821 TI - [Anti-arrhythmia agents]. PMID- 2910822 TI - The value of screening as an approach to cervical cancer control in Iceland, 1964 1986. AB - The effect of screening for cervical cancer on time trends in incidence and mortality from that disease, and the occurrence of pre-invasive cervical lesions during the period 1964-1986, were analyzed. After commencement of screening in 1964 all the above parameters increased for a short initial period but then fell markedly. From 1980, coinciding with a sharp rise in regular attendance rate, there was an increase in incidence up to 1984, followed by a decrease. The rate of pre-invasive stages also increased from 1980, but appears to be levelling off. The cervical cancer mortality rate decreased significantly during the study period. In more recent years, a shift in the occurrence of cervical cancer and pre-invasive lesions from older to younger women has been observed. Screening still appears to be effective in the control of squamous-cell carcinomas of stages I B and over, but not of adeno- and adenosquamous carcinomas. PMID- 2910823 TI - Drug resistance in KHT fibrosarcoma cell lines with different metastatic ability. AB - We have shown previously that tumor cell variants able to form experimental metastases can be generated stochastically in mouse cell lines at high rates and that, in B16 melanoma cell lines, resistance to drugs is associated with metastatic ability. Recently, we reported on the ability of two lines of KHT fibrosarcoma cells derived from individual experimental lung metastases to generate metastatic variants. The KHT 35LI cell line maintained a relatively stable high metastatic ability while the parallel line KHT 3LIc possessed a high metastatic ability when first cultured from the lung but rapidly lost this ability and became a line with a metastatic ability similar to the KHT parental line. Subsequent rate analysis indicated that the rate of generation of metastatic variants was higher for KHT 35LI cells compared to KHT 3LIc or KHT parental cells. Here we examined the ability of these two fibrosarcoma cell lines to generate variants resistant to the drugs methotrexate (MTX) and N (phosphonacetyl)-L-aspartate (PALA). We observed that the highly metastatic KHT 35LI cell line is more resistant to these two drugs than the KHT 3LIc or the parental KHT cell lines. Cloning studies indicated that the likely reason for this increased resistance is that the KHT 35LI cell line generates variants resistant to a given concentration of MTX or PALA at higher rates than the KHT 3LIc or KHT parental cell lines. Since resistance to MTX and PALA usually arises from gene amplification, the results suggest that KHT 35LI cells possess increased ability to amplify their DNA. The association between the rates of generation of both drug-resistant and metastatic variants supports the hypothesis that the mechanism of gene amplification may be involved in the generation of both phenotypes. PMID- 2910824 TI - Hyposialylation of high-molecular-weight membrane glycoproteins parallels the loss of metastatic potential in wheat-germ agglutinin-resistant Friend leukemia cells. AB - From the highly metastatic in vivo-passaged Friend leukemia cells (FLC), WGA resistant (WR) tumor cell variants were selected. These WR FLC had lost their capacity to metastasize when injected i.v. or s.c. into DBA/2 mice. We have characterized the plasma membrane glycoproteins of the different FLC types by: (i) metabolic labelling with (3H)-galactose; (ii) surface labelling with galactose oxidase-borohydride; (iii) direct binding of (125I)-lectins on glycoproteins separated by SDS-PAGE. The ensemble of these approaches showed that the 100- to 200-kDa glycoproteins of in vivo-passaged FLC and WR FLC exhibited a very similar distribution of the terminal galactose in their oligosaccharide moieties. In contrast, the expression of terminal sialic acid was reduced in WR FLC with respect to in vivo-passaged counterparts as appreciated by: (i) binding experiments with (125I)-WGA; (ii) cathodic shift of the 100- to 200-kDa glycoproteins in 2-dimensional electrophoresis studies, and (iii) thiobarbituric acid assay after FLC treatment with neuraminidase. Moreover, binding experiments with (125I)-LPHA, (125I)-ConA and (125I)-WGA (after Smith degradation) indicated that, in the 100- to 200-kDa region, virtually identical asparagine-linked tri- or tetra-antennary complex-type oligosaccharides were expressed in both cell types. We conclude that the sialylation of high-molecular-weight surface glycoproteins (particularly in the 150-kDa region) is strongly associated with the metastatic potential of FLC, especially to the liver. PMID- 2910825 TI - Characterization of a metastasis-deficient lectin-resistant human melanoma mutant. AB - A mutant (3S5), almost completely deficient in pulmonary metastatic ability in nude mice, was recently isolated from a human malignant melanoma cell line (MeWo). The WGA-resistance (WGAr) phenotype of 3S5 cells was accompanied by a collateral hypersensitivity to the lectin BSII (Bandeiraea simplicifolia), similar to that observed previously in class-I non-metastatic WGAr recessive genetic mutants isolated from a highly metastatic mouse tumor. The lectin resistance/sensitivity profile of 3S5 cells was completely stable in tissue culture for 9 months when the cells were grown in the absence of WGA. Twenty independent clones of 3S5 were analyzed and all manifested a similar lectin resistance pattern, and severe deficiency in pulmonary metastatic ability following i.v. or s.c. inoculation, when compared to the parent MeWo cells. Some heterogeneity in metastasis was noted, especially with respect to occasional extrapulmonary spread. The majority of the small number of metastases obtained after i.v. inoculation of 3S5 cells maintained the lectin-resistance profile and deficient metastatic potential characteristic of 3S5 cells upon re-inoculation into other nude mice. The results provide further evidence that cell-surface glycosylation changes can significantly after metastatic potential, including that of human tumors. PMID- 2910826 TI - Action of recombinant alpha interferon against experimental and spontaneous metastases in a murine model. AB - The therapeutic potential of rHuIFN-alpha A/D, a hybrid human IFN molecule with equal activity on murine cells, was studied in experimental and spontaneous metastatic models of a murine colon carcinoma COLON 26. rHuIFN-alpha A/D inhibited experimental pulmonary metastases of COLON 26 and prolonged the survival of BALB/c mice. Dose scheduling, survival and tumour-cell clearance studies showed that the first 5 days were critical in the inhibition of pulmonary metastases. However, it is unlikely that lung NK cells were involved in the anti metastatic effect of rHuIFN-alpha A/D because inhibition of pulmonary metastases and a decrease in radio-labelled tumour-cell survival was seen in BALB/c mice depleted selectively of their NK cells by prior treatment with rabbit antiasialoGMI serum. Although rHuIFN-alpha A/D stimulated NK-cell activity in BALB/c mice, it was ineffective in abrogating the NK suppressant action of rabbit anti-asialoGMI serum on murine lung NK cells. Thus, IFN may mediate its early antimetastatic effect via a mechanism independent of NK-cell stimulation. IFN also inhibited the development of lung metastases from s.c. COLON 26 tumors in normal, NK-depleted and T-cell-deficient mice. PMID- 2910827 TI - Effects of activators of protein kinase C, including bryostatins 1 and 2, on the growth of A549 human lung carcinoma cells. AB - Phorbol esters such as 12-O-tetradecanoylphorbol-13-acetate (TPA) inhibit the growth of A549 human lung carcinoma cells at non-toxic concentrations, whereas 1 oleoyl-2-acetylglycerol and 1,2-dioctanoylglycerol, synthetic analogues of the physiological ligands of protein kinase C (PKC), do not. Experiments were conducted to test the hypothesis that other activators of PKC are capable of interfering with A549 cell growth. The non-phorboid tumour promotor mezerein mimicked the growth-inhibitory effect of TPA in that it arrested growth for 5 days, after which cells proliferated again in the continued presence of the agent. TPA was 20 times more potent as a growth inhibitor than was mezerein. Bryostatin 1 at 10 nM and bryostatin 2 at 100 nM also arrested A549 cell growth and inhibited DNA replication as measured by incorporation of [methyl-3H] thymidine into cells. Inhibition of DNA synthesis to between 90 and 75% of control values developed during the first hour of incubation of the cells with TPA, mezerein or the bryostatins. The extent of inhibition changed little during the subsequent 5 hr of incubation, after which it increased further to reach maximal values within 12 hr. At concentrations above those which caused maximal growth inhibition, the bryostatins abolished both their own inhibition of DNA synthesis and the anti-replicative effect of TPA and mezerein. The results show that activators of PKC other than phorbol esters are capable of inhibiting the growth of A549 cells. The bryostatins not only interfere with A549 cell growth but can also counter the growth-inhibitory effect of PKC activators, presumably via interaction with a target separate from the phorbol ester receptor site. PMID- 2910828 TI - Coffee, alcohol, smoking and cancer of the pancreas: a case-control study. AB - A hospital case control study on smoking, alcohol and coffee consumption as risk factors for pancreatic cancer, in which 161 cases were matched to 268 control patients, was conducted in France between 1982 and 1985. The results showed no association between tobacco or alcohol consumption and cancer of the pancreas, whereas coffee consumption was associated with an increased risk [OR of 2 or more cups per day vs. less: 2.27 (1.11-4.64) and 1.45 (0.82-2.55) among females and males respectively]. A dose-response relationship was observed with coffee consumption in both sexes, stronger among females than among males: the linear increase estimates were 2.00 (1.22-3.29) and 1.32 (0.91-1.92) respectively. No interaction was found between coffee and tobacco, whereas the effect of coffee appeared to be limited to non-drinkers of alcohol. PMID- 2910829 TI - Incidence of male breast cancer in Scandinavia, 1943-1982. AB - Male breast cancer incidence was examined in a collaborative study of data from the cancer registries in Denmark, Finland, Norway and Sweden, comprising a total of 1,529 cases diagnosed from 1943 to 1982. Effects of age, time of diagnosis, birth cohort and country of residence were evaluated by using statistical models of the multiplicative Poisson type. The logarithm of incidence increased linearly with the logarithm of age and had a slope of about 5. In Denmark, male breast cancer incidence increased significantly with time, about 1% per year. No significant time effects were observed in the other countries. A significant effect of birth cohort appeared in Sweden only, but there was no particular trend in incidence by year of birth. In relation to Denmark, the risk of male breast cancer was lower in Sweden, Norway and Finland, the relative risk estimates with 95% confidence intervals being 0.82(0.72-0.94), 0.72(0.61-0.84) and 0.53(0.43 0.64) respectively. The variation within Scandinavia is similar for female breast cancer, pointing to common factors being involved in the etiology of breast cancer in both sexes. PMID- 2910830 TI - Elevated cerebrospinal fluid fibronectin concentration at diagnosis indicates poor prognosis in children with acute lymphoblastic leukemia. AB - We investigated whether the concentration of fibronectin (FN) in the cerebrospinal fluid (CSF) could be used for identifying patients with subclinical blast-cell infiltration in the central nervous system (CNS) and an increased risk of CNS relapse later in the course of their leukemia. Our series comprised 36 children with newly diagnosed acute lymphoblastic leukemia (ALL). The mean follow up time was 54 months (range 5 to 96 months). The median concentration of CSF-FN at diagnosis was 2.24 mg/l (range 0.78 to 7.04 mg/l). The 3-year continuous complete remission rate for the 16 patients with CSF-FN concentrations less than or equal to 2 mg/l was 93% as compared with 37% for the 19 patients with CSF-FN greater than 2 mg/l (p = 0.001). When multivariate analysis was performed, the CSF-FN concentration retained its prognostic significance. When all relapses were considered as failures, the relative risks of relapse for patients with CSF-FN less than or equal to 2 mg/l and greater than 2 mg/l were I and 15.8 (95% confidence limits 1.8-135.6, p less than 0.02), respectively. If only CNS relapses (isolated and combined) were considered as failures, relative risks for the above-mentioned groups were I and 11.6 (1.4-99.5, p less than 0.05), respectively. We conclude that determination of the CSF-FN concentration may provide a new means of evaluating the CSF in children with ALL and may prove to be a sensitive indicator of leukemic CNS infiltration. PMID- 2910831 TI - Soft-tissue sarcoma, non-Hodgkin's lymphoma and other cancers in New Zealand forestry workers. AB - Several studies have suggested that forestry workers are at increased risk for certain types of cancer including soft-tissue sarcoma (STS) and non-Hodgkin's lymphoma (NHL). We now report a series of national case-control studies based on the New Zealand Cancer Registry (NZCR). These involved 19,904 male patients with cancer for the period 1980-1984 who were aged 20 years or more at the time of registration. For each cancer site, the registrations for the remaining sites formed the control group. Current or most recent occupational titles were coded. There was an increased risk for STS (OR = 3.24) in forestry workers which was confined to men under 60 years of age at registration. An elevation in risk for NHL (OR = 1.84) was due to an increase in risk for lymphosarcoma and reticulosarcoma (ICD 200) (OR = 3.18). Acute myeloid leukemia was also associated with forestry work, although the estimate of risk was imprecise (OR = 2.24). Among other cancer sites, an increase in risk of neoplasia of the upper gastro intestinal tract (ICD 150, 151, 152) was demonstrated. Odds ratios were elevated for cancer of the esophagus (OR = 1.77), stomach (OR = 2.22), small intestine (OR = 5.22), gall-bladder (OR = 4.13) and pancreas (OR = 1.79), as well as for nasopharyngeal cancer (OR = 5.56). These increases in cancer risk were not present in sawmill workers in New Zealand during the same period. The factors responsible for the increased cancer risks in forestry workers remain unclear and require further study. PMID- 2910832 TI - Immunosuppressive activity of human neuroblastoma tumor gangliosides. AB - Gangliosides are shed in substantial amounts by some tumors, including human neuroblastoma, and these molecules modulate experimental tumor formation in vivo. We now demonstrate that neuroblastoma tumor gangliosides have potent immunoregulatory activity. Gangliosides of every one of 17 tumors studied were highly inhibitory for the normal in vitro human lymphoproliferative responses to the soluble antigen, tetanus toxoid; 30 nmol ganglioside/ml caused 43% to greater than 99% inhibition and the mean concentration causing 50% inhibition was only 17.3 nmol/ml. Furthermore, gangliosides isolated from clinically more aggressive tumors (Stage III or IV) were up to twice as immunosuppressive as those of the generally less aggressive tumors (Stage I or II) (p less than 0.05). Taken together with the lack of immunosuppressive activity of normal plasma gangliosides, the potent activity of neuroblastoma gangliosides supports the hypothesis that one mechanism by which these shed molecules may act to enhance tumor formation in vivo is through abrogation of the host cellular immune response at the site of tumor formation. PMID- 2910833 TI - Chromosomal aberrations in lymphocytes of patients treated with melphalan. AB - Chromosome lesions detected in lymphocytes from 14 patients previously treated with melphalan, a bifunctional alkylating agent, have been analyzed on R-banded preparations. In comparison to controls, there was no significant increase of chromatid-type lesions, but chromosome-type lesions were quite frequent, affecting 21.5% of metaphases, on the average. Reciprocal translocations represent 54%, unbalanced translocations 15%, deletions 19% and inversions 6% of all rearrangements. Most of these would not have been detected without the use of chromosome banding. The distributions of affected chromosomes and chromosome bands were not random. Almost all imbalances resulting from rearrangements lead to losses but not to gains. The distribution of the abnormal chromosomes has been compared to that observed in controls and in in vitro experiments, and to the characteristic pattern of malignant cells from patients affected by secondary acute leukemia (ANLL). PMID- 2910834 TI - Glycosphingolipids in lectin-resistant variants of mouse Lewis lung carcinoma cells. AB - Neutral glycolipids and gangliosides from murine Lewis lung carcinoma cell line LL2 and its lectin-resistant variants, differing in metastatic properties, were studied by fast-atom-bombardment mass spectrometry (FAB-MS), exoglycosidase treatment and an immunostaining procedure. The neutral glycolipids identified in all cell lines studied included CMH, CDH, CTH, asialo GM2, globoside and a glycolipid with a preliminary structure of Hex-Hexl-4HexNAc-Hex-Hex-Cer. The major gangliosides were GM3, GM2, GM1 and GD1a. No qualitative differences in glycosphingolipid expression were found between the metastatic cell lines (LL2 and LL2AAA) and the weakly metastatic variants (LL25, LL28, LL230 and LL2RCA II). Some quantitative differences were observed between the cell lines, e.g., in the level of ganglioside-bound sialic acid, which was not apparently correlated with the metastatic capacities. PMID- 2910835 TI - Inability to predict postdexamethasone cortisol levels by serum sodium levels. AB - Each of 42 hospitalized patients with unipolar major depression received a dexamethasone suppression test (DST) and had blood drawn for serum sodium and potassium tests within 3 days of admission. Unlike the patients in an earlier report by Tollefson et al., these patients showed no correlations between the DST results and the serum sodium levels. Although the DST identified depressive subtypes accurately, the serum sodium levels did not predict the DST results in this study. PMID- 2910836 TI - Fear episodes due to limbic seizures with normal ictal scalp EEG: a subdural electrographic study. AB - The authors present the case of a 13-year-old girl with episodes characterized by either staring with preserved consciousness or fear in whom functional illness was suspected. Video-EEG telemetry revealed no changes during 30 of 32 attacks. Subdural electrode recordings revealed epileptiform discharges in 30 of 37 episodes. The discharge was always localized to the electrodes recording from the inferomedial temporal region, with electrodes over the lateral convexity of the same temporal lobe showing no background changes. Although the detailed pathophysiology of panic attacks remains to be clarified, the authors point out that their case and other epileptic case studies are consistent with the possibility that excessive neuronal activity in medial temporal lobe structures is a necessary element of the underlying mechanism. PMID- 2910837 TI - Anabolic-androgenic steroid dependence. AB - The authors believe that this is the first published case report of a patient whose dependence on a combination of anabolic and androgenic steroids meets the DSM-III-R criteria for psychoactive substance dependence. Tolerance, withdrawal symptoms, and the use of steroids to alleviate withdrawal symptoms occurred. An uncontrolled pattern of steroid use continued, despite adverse consequences, such as severe mood disturbance, marital conflict, and deterioration of the patient's usual values. Clinicians should be alerted to the possibility of dependence when asked to prescribe anabolic or androgenic steroids and should suspect steroid use among athlete patients who have mood or psychosocial disturbances. PMID- 2910838 TI - Tolerance to phenelzine and subsequent refractory depression: three cases. AB - Three patients with major depression superimposed on chronic dysthymia were treated with phenelzine. After an initial excellent response, each patient relapsed and developed a severe chronic depression that was refractory to other treatments. The implications for the long-term effects of phenelzine treatment are considered. PMID- 2910839 TI - Tricyclics: adequate trials and plasma levels. PMID- 2910840 TI - Death by Freon. PMID- 2910841 TI - Analysis of calcium homeostasis in activated human polymorphonuclear leukocytes. Evidence for two distinct mechanisms for lowering cytosolic calcium. AB - The stimulation of polymorphonuclear leukocytes (PMNs) by chemoattractants triggers a rapid rise in cytosolic free calcium concentration(s) ([Ca2+]i), which quickly returns to base line, suggesting a role for calcium removal in the homeostasis of activated PMNs. To investigate cytosolic calcium homeostasis, PMNs were treated with a fluoroprobe and ionomycin to induce a sustained elevation of [Ca2+]i. The cells were then stimulated, and attenuation of the fluorescence signal was measured as an indication of calcium loss from the cytosol. The formyl peptide chemoattractant N-formyl-methionyl-leucyl-phenylalanine (fMLP), phorbol myristate acetate (PMA), and 1,2-dioctanoyl-sn-glycerol, but not the inactive phorbol ester 4 alpha-phorbol didecanoate, induced a dose-dependent decrease in [Ca2+]i in ionomycin-pretreated cells. However, the decline in [Ca2+]i caused by PMA was sustained and occurred following a lag time, whereas the response to fMLP was immediate, lasted approximately 2 min, and then was followed by a return of [Ca2+]i to its initial level. The restoration of [Ca2+]i required extracellular calcium. Varying the ionomycin concentration allowed studies at different initial [Ca2+]i, which in untreated PMNs was approximately 135 nM. In contrast to fMLP, PMA did not lower calcium at concentrations below 200 nM. The decline in [Ca2+]i induced by fMLP, but not PMA, was blocked by pertussis toxin. In contrast, the decrease in [Ca2+]i caused by PMA and 1,2-dioctanoyl-sn-glycerol, but not fMLP, was inhibited by the protein kinase C antagonists staurosporine, H-7, and sphingosine. These results suggest that formyl peptide chemoattractants transiently stimulate an activity which lowers [Ca2+]i to normal intracellular levels. Activation of this process appears to be independent of protein kinase C. An additional cytosolic calcium lowering activity, dependent on protein kinase C, operates at [Ca2+]i above 200 nM. Thus, activated PMNs can use at least two processes for attentuation of elevated cytosolic calcium levels. PMID- 2910842 TI - Novel O-linked carbohydrate chains in the cellulase complex (cellulosome) of Clostridium thermocellum. 3-O-Methyl-N-acetylglucosamine as a constituent of a glycoprotein. AB - Alkaline borohydride treatment of the cellulosome of Clostridium thermocellum yielded two major oligosaccharide-alditols, namely D-Galp-beta(1----4)-D-GalOH and (formula; see text) The compounds, isolated via gel permeation chromatography and high performance liquid chromatography, were analyzed by monosaccharide analysis, methylation analysis, gas-liquid chromatography/mass spectrometry, fast atom bombardment/mass spectrometry, and one- and two-dimensional 500-MHz (COSY, HOHAHA, ROESY) 1H NMR spectroscopy. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis combined with blotting technology indicated that the tetrasaccharide is mainly associated with one of the cellulosome subunits. PMID- 2910843 TI - Enzymatic conversion of prostaglandin H2 to prostaglandin F2 alpha by aldehyde reductase from human liver: comparison to the prostaglandin F synthetase from bovine lung. AB - The primary structure of prostaglandin (PG) F synthetase from bovine lung shows 62% similarity with that of human liver aldehyde reductase (EC 1.1.1.2) (Watanabe, K., Fujii, Y., Nakayama, K., Ohkubo, H., Kuramitsu, S., Kagamiyama, H., Nakanishi, S., and Hayaishi, O. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 11 15). We therefore purified human liver aldehyde reductase to homogeneity and compared the immunological and catalytic properties of aldehyde reductase and PGF synthetase. Although both enzymes belong to a group of aldoketoreductases and their molecular weights are essentially identical, aldehyde reductase had no cross-reactivity to anti-PGF synthetase antiserum. Furthermore, there was a difference in the substrate specificity for reduction of PGs between the two enzymes. Aldehyde reductase catalyzed the reduction of PGJ2, delta 12-PGJ2, PGH2, or PGA2, but not that of PGB2, PGD2, or PGE2, whereas PGF synthetase reduced PGD2. The optimum pH, Km value for PGH2, and the turnover number were 6.5, 100 microM, and 3.1 min-1, respectively. The PGH2 9,11-endoperoxide reductase activity of aldehyde reductase was not affected in the presence of a substrate such as p-nitrobenzaldehyde, DL-glyceraldehyde, or 9,10-phenanthrenequinone, suggesting that PGH2 9,11-endoperoxide and other substrates are reduced at different active site(s). The reaction product formed from PGH2 by this enzyme was identified as PGF2 alpha by gas chromatography/mass spectrometry. These results suggest that aldehyde reductase is not exactly identical to PGF synthetase in terms of its immunological property and substrate specificity for PGs, but that this enzyme is also involved in the direct conversion of PGH2 to PGF2 alpha similar to PGF synthetase. PMID- 2910844 TI - Synthesis of single-stranded plasmid pT181 DNA in vitro. Initiation and termination of DNA replication. AB - The origin of replication of plasmid pT181 is nicked by the plasmid-encoded RepC protein. The free 3'-hydroxyl end at the nick is presumably used as primer for leading strand DNA synthesis. In vitro replication of pT181 was found to generate single-stranded DNA in addition to the supercoiled, double-stranded DNA. The single-stranded DNA was circular and corresponded to the pT181 leading strand. Recombinant plasmids were constructed that contain two pT181 origins of replication in either direct or inverted orientation. In vitro replication of the plasmid carrying two origins in direct orientation was shown to generate circular, single-stranded DNA that corresponded to initiation of replication at one origin sequence and termination at the other origin. These results demonstrate that the origin of pT181 leading strand DNA replication also serves as the site for termination of replication. Interestingly, the presence of two origins in inverted orientation resulted in initiation of replication at one origin and stalling of the replisome at the other origin. These results suggest that RepC can reinitiate replication at the second origin by nicking partially replicated, relaxed DNA. These data are consistent with the replication of pT181 by a rolling circle mechanism and indicate that single-stranded DNA is an intermediate in pT181 replication. PMID- 2910845 TI - Anomalies in the translocation and processing of glycophorin precursors in murine erythroleukemia cells. AB - Analogues of human glycophorins have been identified in many species, including mouse. In murine erythroleukemia cells three mature glycophorins (gp-2, gp-3, 34K) and four putative precursors (21K, 23K, 26K, and 27K) are expressed. Pulse chase labeling experiments suggest that 21K and 23K are the precursors of the gp 3 doublet of proteins 29K and 30K. Precursor-product relationships were not found for 26K, 27K, 34K, and gp-2. Two experimental approaches, i.e. cell-free translation and subcellular distribution, have identified processing anomalies in the glycophorins. First, signal sequences, if present, are apparently not cleaved upon translocation across the endoplasmic reticulum membrane; second, the 26K and 27K putative precursors are inefficiently translocated. The majority accumulates in the cytosol or associates with the endoplasmic reticulum membrane without acquiring protection against V8 protease. Only a minority (approximately 10%) is properly translocated. PMID- 2910846 TI - Interphotoreceptor retinoid-binding protein. Gene characterization, protein repeat structure, and its evolution. AB - The gene for bovine interphotoreceptor retinoid-binding protein (IRBP) has been cloned, and its nucleotide sequence has been determined. The IRBP gene is about 11.6 kilobase pairs (kb) and contains four exons and three introns. It transcribed into a large mRNA of approximately 6.4 kb and translated into a large protein of 145,000 daltons. To prove the identity of the genomic clone, we determined the protein sequence of several tryptic and cyanogen bromide fragments of purified bovine IRBP protein and localized them in the protein predicted from its nucleotide sequence. There is a 4-fold repeat structure in the protein sequence with 30-40% sequence identity and many conservative substitutions between any two of the four protein repeats. The third and fourth repeats are the most similar pair. All three of the introns in the IRBP gene fall in the fourth protein repeat. Two of the exons, the first and the fourth, are large, 3173 and 2447 bases, respectively. The introns are each about 1.5-2.2 kb long. The human IRBP gene has a sequence that is similar to one of the introns from the bovine gene. The unexpected gene structure and protein repeat structure in the bovine gene lead us to propose a model for the evolution of the IRBP gene. PMID- 2910847 TI - In vitro synthesis, phosphorylation, and localization on 48 S initiation complexes of human protein synthesis initiation factor 4E. AB - Complementary DNA for human eukaryotic initiation factor 4E (eIF-4E) was transcribed in vitro and the transcripts used to direct protein synthesis in a cell-free reticulocyte translation system. The predominant translation product was 25 kDa, was bound to a m7GTP-Sepharose affinity column, and was specifically eluted with m7GTP. Both phosphorylated (P) and unphosphorylated (U) forms of eIF 4E were synthesized, and the P/U ratio increased as a function of incubation time in the reticulocyte lysate system. Both forms were quantitatively retained on m7GTP-Sepharose. When translation reactions were resolved on sucrose density gradients, the 35S-labeled eIF-4E sedimented predominantly at 3-4 S. However, in the presence of edeine or guanylyl imidodiphosphate, both of which cause accumulation of 48 S initiation complexes, eIF-4E was detected in the 48 S region. In the presence of sparsomycin, used to accumulate 80 S initiation complexes, no eIF-4E was observed in the 80 S region. No change in the eIF-4E distribution was caused by m7GTP. These results are consistent with a model whereby eIF-4E is transferred to the 43 S initiation complex together with mRNA and is released from the initiation complex when the 60 S ribosomal subunit joins. PMID- 2910848 TI - Multiple protein-DNA interactions within the human interferon-beta regulatory element. AB - High efficiency nuclear protein extracts were prepared from uninduced and recombinant interferon (IFN-alpha 2-primed Sendai virus-induced HeLa S3 cells and analyzed for DNA binding proteins specific for the human interferon-beta regulatory element (IRE). Analysis of protein-DNA interactions by a gel electrophoresis DNA binding assay resolved three complexes (designated A, B, and C) specific for the IRE probe (-79 to -36) in uninduced and induced cells. Competition studies using greater than a 100-fold molar excess of unlabeled DNA fragments representing different IFN-beta promoter sequences localized the DNA binding domain to the region -79 to -64 (P1 probe), a region previously shown to be essential for virus-inducible gene expression. Other adjacent IFN-beta segments including the negative regulatory element (-65 to -30) as well as the SV40 enhancer, c-fos serum-responsive element, and IFN-alpha 1 promoter fragment (-131 to -71) were unable to compete for the IRE binding protein. The 16-base pair enhancer core (P1 probe) specifically bound similar amounts of protein from uninduced and induced extracts; a synthetic tetrahexamer, AAGTGA, competed efficiently for the binding to the P1 region. Competition studies indicated that adjacent upstream IFN-beta DNA sequences -94 to -78 (P5) also contained a sequence motif capable of binding the P1 protein. In vitro transcription of the IFN-beta template in the HeLa nuclear extracts was partially inhibited when increasing amounts of competitor IRE fragment were added to the reaction. These results demonstrate that multiple DNA sequence motifs within the IFN-beta regulatory element interact to bind transcription regulatory proteins which are present in normal and virus-infected HeLa cells. PMID- 2910849 TI - Protein kinase C located in rat liver nuclei. Partial purification and biochemical and immunochemical characterization. AB - In the rat liver homogenate, maximal protein kinase C activity was found at two calcium concentrations (1.75 and 3.5 mM). Subcellular fractionation of the liver homogenate revealed that the protein kinase C activity requiring 1.75 mM calcium was present only in the cytosolic and particulate subcellular fractions. The protein kinase C activity requiring 3.5 mM calcium concentration was mainly located in the rat liver nuclei preparation. About 19% of the liver homogenate protein kinase C activity requiring 3.5 mM calcium was present in the nuclei. Goat anti-rat brain protein kinase C antibodies revealed a single immunoreactive band at 80-82 kDa in the rat liver nuclear, particulate, or cytosolic fractions. Based on the ratio of plasma membrane marker enzyme activity determined in the nuclear preparation, the purity of the isolated nuclei was ascertained. Rat liver nuclear protein kinase C activity has been partially purified. The purification steps sequentially employed were Triton X-100 extraction of isolated nuclei, DEAE cellulose chromatography, Phenyl-Superose, and Mono Q (fast protein liquid) chromatography. The final purification step revealed, by silver nitrate staining on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, two protein bands at 80 and 66 kDa, respectively. These findings provide definitive data regarding the nuclear location of protein kinase C. The nuclear location of protein kinase C may lead to an understanding of the molecular pathway involved in signal transduction from the plasma membrane to the nucleus. PMID- 2910850 TI - Phosphatidylethanolamine levels and regulation of phosphatidylethanolamine N methyltransferase. AB - The activity of phosphatidylethanolamine (PE) N-methyltransferase in liver microsomes, measured using endogenous microsomal PE as a substrate, was elevated 2-fold in the choline-deficient state. However, methyltransferase activity assayed in the presence of a saturating concentration of phosphatidyl-N-mono methylethanolamine or microsomal PE was unchanged by choline deficiency. Accompanying the increase in methyltransferase activity in liver homogenates and microsomes were increased PE concentrations and an increased PE to phosphatidylcholine ratio. The concentration of other phospholipids was unchanged. Immunoblot analysis of choline-deficient and choline-supplemented rat liver microsomes using a rabbit polyclonal anti-PE N-methyltransferase antibody revealed that the amount of enzyme protein was unaltered. The regulation of methyltransferase by PE levels was also investigated in cultured hepatocytes obtained from choline-deficient rat livers. Supplementation of deficient hepatocytes with 200 microM methionine resulted in a 50% reduction in cellular PE levels over a 12-h period. PE N-methyltransferase activity assayed with endogenous PE was also reduced by 50%, but phosphatidyl-N-monomethylethanolamine dependent activity was unchanged. A 4-h supplementation with choline did not affect PE levels or methyltransferase activity. Either methionine or choline supplementation resulted in net synthesis of cellular phosphatidylcholine. Immunoblotting of membranes from methionine-supplemented hepatocytes revealed no change in enzyme protein, a further indication that enzyme mass was constitutive, and activity was regulated by the concentration of PE. PMID- 2910851 TI - Fine mapping of the chromatin structure of a cell cycle-regulated human H4 histone gene. AB - We have observed changes in the chromatin structure of a human histone gene promoter that may be functionally related to variations in transcription during the cell cycle. A detailed analysis of the chromatin structure of a cell cycle dependent human H4 histone gene and its flanking sequences was performed using DNase I, S1 nuclease, and restriction endonucleases. This gene was previously shown to have a DNase I- and S1-sensitive site for which the boundaries varied with the cell cycle, and we have now precisely mapped these modifications. During S phase, the entire coding region of this gene and the 5'-flanking region up to approximately -600 base pairs are sensitive to both DNase I and S1, while during mitosis/G1, accessibility to these enzymes is greatly decreased in regions from 250 to -600 base pairs and downstream of +100 base pairs. DNase I- and S1 hypersensitive sites in the proximal promoter region (which contains two sites of protein-DNA interaction as well as sequence elements necessary for the correct initiation of transcription) are present throughout the cell cycle, as is an additional site sensitive to both DNase I and S1, located at -700 to -800 base pairs. Restriction enzyme analysis confirmed the general openness of the promoter region and relative insensitivity of the 3'-flanking region, while salt wash experiments indicated several discrete sites in the promoter that are candidates for regulatory interactions. The chromatin structure of the proximal promoter region of this H4 gene is different during early S phase when it is maximally transcribed, as indicated by the ability of a high salt wash to render this region inaccessible to the restriction enzyme MspI only at this time of the cell cycle. PMID- 2910852 TI - Interactions among serum vitamin D binding protein, monomeric actin, profilin, and profilactin. AB - Human serum vitamin D binding protein (hDBP), a 58-kDa inter-alpha-globulin, is known to bind, monomeric actin (G-actin) in equimolar quantities. Using monoclonal and polyclonal anti-hDBP antibodies, hDBP, and radioiodinated actin, we developed a reliable saturation assay for actin bound to hDBP. By utilizing this assay, kinetic analysis, and ultracentrifugal sedimentation in sucrose gradients, these proteins' binding affinities (Kd = 10(-9) M) were demonstrated to be 10- to 100-fold greater than earlier estimates. At 4 degrees C, hDBP has an association rate constant of 2.2 x 10(4) M-1 s-1 and a rate of dissociation displaying a t1/2 of 22 h. This high affinity binding was largely unaffected by conditions favoring actin filament formation (1 mM MgCl2 and/or 50 mM KCl), by the range of pH from 6.8 to 8.6 or by temperatures from 4 to 37 degrees C. Compared with ATP-alpha-actin, a 2-fold decrease of binding affinity was observed for the nonmuscle isoactins (beta,gamma), ADP-G-alpha-actin, and N' ethylmaleimide-modified G-alpha-actin. The 25-hydroxyvitamin D3 and 1 alpha,25 dihydroxyvitamin D3 holo-sterol forms of hDBP bound actin in a manner indistinguishable from the apo-sterol hDBP. The common polymorphisms of hDBP (DBP1 slow, DBP1 fast, and DBP2) were shown to have an equal avidity for G-actin binding. Human platelet profilin competed with hDBP for binding to G-actin, but was 1000-fold less potent (Ki = 1.9 microM). When platelet profilactin was incubated with hDBP, profilin was liberated and hDBP-actin complexes formed. DNase I, which forms a triprotein complex with hDBP-G actin, did not alter the affinity of binding of actin by hDBP. The very high affinity binding observed, which was largely unaffected by the state of G-actin, pH, and ionic conditions, appears to support a constitutive role for plasma DBP in the sequestration of actin monomers, as well as actin from actin-profilin complexes, that are liberated during cell injury. PMID- 2910853 TI - Identification and characterization of a factor that binds to two human sarcomeric actin promoters. AB - A gel mobility shift assay was used to examine nuclear extracts of muscle and nonmuscle cell lines for a factor or factors that interact with the functional promoter segment of both the human cardiac and skeletal alpha-actin genes. A single major band of altered mobility was seen with nuclear extracts from C2 myoblasts and myotubes and L8 myoblasts and myotubes as well as several non muscle cell lines. Competition experiments with nuclear extracts from both muscle and non-muscle cells localized the region of binding to a 10-base pair sequence of the cardiac alpha-actin gene containing the functional CArG box promoter domain. Similar results and binding site specificities were obtained with a DNA fragment from the human skeletal alpha-actin promoter. The CArG box binding factor was shown to be distinct from a CAAT box binding factor. A molecular weight of 67 kDa for the CArG box binding factor was determined by photoaffinity labeling of the complex and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Protease treatment resulted in a smaller fragment that still bound the cardiac alpha-actin promoter fragment and may represent a structurally distinct DNA-binding domain. We discuss how muscle-specific expression of the sarcomeric alpha-actin genes might be achieved with a ubiquitous transcription factor. PMID- 2910854 TI - Purification and characterization of a 40 S ribosomal protein S6 kinase from vanadate-stimulated Swiss 3T3 cells. AB - Recently we have identified a mitogen-activated S6 kinase from Swiss 3T3 cells (Jeno, P., Ballou, L. M., Novak-Hofer, I., and Thomas, G. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 406-410). Here we describe the detailed purification of this enzyme from high-speed supernatants (400,000 x g) of vanadate-treated cell extracts. The enzyme is purified through six sequential steps including cation- and anion-exchange, sizing, and affinity chromatography. At each step, the enzyme behaves as one entity and, on the final step of purification, is revealed on silver-stained sodium dodecyl sulfate-polyacrylamide gels as a single protein of Mr 70,000. As reported earlier, the overall purification factor is 3,000-fold, and the specific activity of the homogeneously purified enzyme is 0.6 mumol/min/mg of protein. However, recovery of total activity is only 0.2%. This large loss of activity appears to be due to freeze-thawing the enzyme between each step of purification. The purified kinase does not phosphorylate casein, histones 2A and 3S, or phosvitin. It has a Km for ATP of 28 microM and a broad optimum for Mg2+ between 5 and 20 mM. Mn2+ does not affect the basal level of kinase activity, and at concentrations as low as 1 mM, it completely suppresses the effect of 20 mM Mg2+ on kinase activity. The relationship of this enzyme to two other purified S6 kinases is discussed. PMID- 2910855 TI - Regulation of low density lipoprotein receptor gene expression in human lymphocytes. AB - Cholesterol homeostasis is maintained by coordinate regulation of endogenous synthesis and exogenous uptake of lipoprotein cholesterol by low density lipoprotein (LDL) receptors. In the lymphocyte, limiting the availability of exogenous cholesterol is known to increase the rate of endogenous sterol biosynthesis. However, the effect of cholesterol deprivation on the expression and regulation of the LDL receptor gene has not been delineated in lymphocytes. Here, LDL receptor mRNA was detected in freshly isolated human peripheral mononuclear cells. LDL receptor mRNA levels increased by 3-fold during a one-h in vitro culture in lipoprotein-deficient medium and by 6-fold during a 2-h incubation. Actinomycin D blocked the synthesis of LDL receptor mRNA in these cultures. However, neither cycloheximide nor LDL or oxygenated sterols suppressed the increase in LDL receptor mRNA levels observed after a 2-h incubation. The increase in LDL receptor mRNA was maintained for 24 h of culture in the absence of LDL. Ongoing gene transcription and not mRNA stabilization accounted for this expression. Inhibition of protein synthesis with cycloheximide completely prevented the sustained increase in LDL receptor mRNA levels measured after 24 h. Low concentrations of LDL (5 micrograms of cholesterol/ml) and oxygenated sterols also suppressed the level of LDL receptor mRNA measured after a 24-h incubation. These data show that the initial upregulation of LDL receptor gene expression is independent of protein synthesis and not suppressed by either LDL or oxygenated sterols. In contrast, the continued transcription necessary for the maintenance of steady-state levels of LDL receptor mRNA requires synthesis of new protein and is regulated by LDL and oxygenated sterols. PMID- 2910856 TI - Molecular cloning, characterization, and expression of a human 14-kDa lectin. AB - Full length cDNAs coding for a 14-kDa beta-galactoside binding lectin have been isolated from HL-60 cells and human placenta. Oligonucleotide probes based on a pentapeptide present in several partial sequences of homologous human lectins were used to screen a lambda GT10 HL-60 cDNA library. The HL-60 cDNA clones that were isolated were used to design a synthetic primer representing the 3' untranslated region of the HL-60 lectin. This primer was then used to synthesize a lambda GT10 human placenta cDNA library, and restriction fragments of the HL-60 cDNA clones were used to screen the library. The cDNA clones for both HL-60 and placenta lectin had identical sequences with short 5'- and 3'-untranslated regions and coded for a 135-amino acid protein which lacks a hydrophobic signal peptide sequence. Biochemical data show that, despite the presence of a possible N-linked glycosylation site, the protein is not glycosylated. Northern and Southern blot analyses indicate that the 14-kDa lectin is encoded for by a single gene. The lectin cDNA was expressed in Escherichia coli and biologically active protein was purified from cell lysates by affinity chromatography. PMID- 2910857 TI - Multiplicity of heme oxygenase isozymes. HO-1 and HO-2 are different molecular species in rat and rabbit. AB - We report on the detection and characterization of two forms of heme oxygenase in rabbit tissues and provide data suggesting that heme oxygenases in rat and rabbit are not identical and constitute a group of heterogenous proteins. Certain molecular properties, however, are shared by the isozymes in rat and rabbit; the predominant form of the enzyme in control liver and testis is HO-2, in the liver HO-1 is the inducible form, and in the brain HO-1 is not detectable. HO-1 was purified from liver of rabbits treated with bromobenzene to near homogeneity with a specific activity of 8,270 nmol of bilirubin/mg/h and compared with a homogenous preparation of rat HO-1 with a specific activity of 6,220, also obtained from bromobenzene-treated animals. Rat and rabbit HO-1, on sodium dodecyl sulfate-polyacrylamide gel, had molecular weights of 30,000 and 30,700, respectively. Rabbit HO-2 was partially purified from testis to a specific activity of 386 nmol of bilirubin/mg/h and compared with a purified preparation of rat testis HO-2 with a specific activity of 5,700. Using Western immunoblotting, rabbit HO-2 displayed intense cross-reactivity with antibody raised in rabbit to sodium dodecyl sulfate-denatured rat HO-2, and had a substantially larger molecular weight than the rat HO-2 (42,000 versus 36,000). Rabbit HO-1 did not cross-react with antibody to rat HO-1 which was also raised in rabbit. Unlike the rat enzymes, rabbit HO-1 and HO-2 did not differ in thermolability. It is speculated that HO-1 in rat and rabbit, and possibly HO-2, have evolved from divergent evolution of a common ancestral gene(s). PMID- 2910858 TI - Platelet-derived growth factor-inducible gene JE is a member of a family of small inducible genes related to platelet factor 4. AB - The platelet-derived growth factor-inducible gene JE was found to encode a 148 residue basic (pI = 10.4) secretory protein which shows striking similarity to the gene products of a family of small inducible genes (SIG), LD78, TCA3, IP10, 3 10C, 9E3/pCEF4, and gro/MGSA, and to several of the proteins secreted from platelet alpha-granules. Members of the SIG family have spatially conserved cysteine residues that vary in distance by only one amino acid residue as well as conserved proline residues at analogous sites. Hydrophilicity plots show alternating hydrophobic and hydrophilic domains which are similar for all members of the SIG family except IP10 and platelet factor 4, which show similarities to each other. The genomic organization of SIG family members is similar in the location of the splice junctions and the number of introns and exons, suggesting that they were derived from a common ancestor. The collective evidence suggests that a family of inducible cytokines, which are mitogenic or chemotactic, may act as intercellular coordinators of diverse responses designed to combat infection and promote the healing and regeneration of injured tissue. PMID- 2910859 TI - Biogenesis of the somatogenic receptor in rat liver. AB - Certain structural characteristics, in particular the type of oligosaccharide chains associated with the rat liver somatogenic (GH) receptors, were studied in different isolated organelles involved in receptor biosynthesis, maturation, and binding, with the use of ligand-affinity cross-linking, incubation with various oligosaccharide chain-cleaving enzymes, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In an endoplasmic reticulum-enriched fraction, a somatogenic receptor with Mr 33,000, after correction for bound ligand (assuming a 1:1 binding ratio of ligand to receptor) was found to contain N-linked high mannose oligosaccharide chain(s). In an intermediate density fraction, enriched in cis Golgi, a major receptor of Mr 43,000 was found to contain N-linked complex type of oligosaccharide chains. In a low density membrane fraction, containing trans Golgi complex membranes and endocytic vesicles, three receptors of Mr 95,000, 55,000, and 43,000 were found. These three receptors contain N-linked complex type oligosaccharide chains. Neuraminidase treatment resulted in a decrease of the Mr 95,000 and 43,000 receptors to Mr 81,000 and 39,000, respectively. Two specific somatogenic receptors of Mr 95,000 and 43,000 containing N-linked complex type of oligosaccharides were found in an isolated plasma membrane enriched fraction. When isolated hepatocytes were analyzed, the Mr 95,000 receptor was found to be the major labeled species. Two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis (first dimension nonreducing and the second dimension reducing conditions), showed that the Mr 43,000 receptor is contained within the Mr 95,000 receptor. The data suggest that the Mr 33,000 receptor found in endoplasmic reticulum constitutes a precursor to the Mr 43,000 receptor and that the Mr 43,000 receptor is complexed with an unknown subunit during transport through the Golgi complex to form an Mr 95,000 receptor present on the cell surface. PMID- 2910860 TI - Role of intracellular pH in secretion from adrenal medulla chromaffin cells. AB - The role of intracellular pH in stimulus-secretion coupling was investigated in cultured bovine adrenal medullary chromaffin cells. NH4Cl (1-25 mM) did not affect basal catecholamine or ATP release but markedly inhibited nicotine- or high K+-induced release by up to 60%. The inhibition had a rapid onset (less than 1 min) and was maximal at about 5 mM NH4Cl. The effect of NH4Cl was largely sustained over 20 min and was reversed upon NH4Cl removal. Sodium propionate did not affect secretion but partially reversed the inhibition by NH4Cl in a concentration-dependent manner. Methylamine (10 mM) produced a similar, but slower, inhibition than NH4Cl. Monensin (1-10 microM) inhibited catecholamine secretion by 30-60%, and its effect was reduced in the presence of NH4Cl. Using the fluorescent Ca2+ probe Fura-2, we found that the increase of [Ca2+]i following stimulation was not altered by concentrations of NH4Cl which inhibited secretion maximally. Measurement of cytosolic pH (pHi) with the fluorescent probe 2',7'-bis-carboxyethyl-5(6)-carboxyfluorescein (BCECF) revealed an alkalinization by NH4Cl (2.5-25 mM) of 0.1-0.23 pH units and acidification by sodium propionate (10-20 mM) of 0.2-0.25 pH units, with intermediate combined effects. Monensin (1 microM) caused a cytosolic acidification of 0.26 pH units. All pHi changes were partly recovered in 15 min. Fluorescence quenching measurements using the weakly basic fluorescent probe acridine orange indicated the accumulation of the probe into acidic compartments, presumably the chromaffin granules, which was strongly reduced by both NH4Cl and monensin. From these findings we conclude that the pH of the chromaffin granule modulates secretion by affecting some step in the secretory process unrelated to the rise in [Ca2+]i. PMID- 2910861 TI - Cyclopentenylcytosine triphosphate. Formation and inhibition of CTP synthetase. AB - Cyclopentenylcytosine (CPEC) is phosphorylated in L1210 cells with CPEC triphosphate as the major metabolite. Partially purified uridine-cytidine kinase catalyzes the initial phosphorylation of cyclopentenylcytosine with an apparent Km of 196 +/- 9 microM, and cyclopentenylcytosine is a competitive inhibitor of cytidine phosphorylation by this enzyme with a Ki value of 144 +/- 14 microM. Examination of the CTP synthetase activity in extracts of L1210 cells revealed a dose-dependent decrease on exposure of cells to CPEC. Synthesis of CPEC triphosphate by an enzymatic method permitted direct examination of the inhibition of partially purified CTP synthetase. CPEC triphosphate inhibited bovine CTP synthetase with a median inhibitory concentration of 6 microM, whereas CPEC mono- and diphosphates were ineffective. CTP synthetase showed a classical Michaelis-Menten hyperbolic plot of velocity and UTP concentration in the presence of saturating concentrations of ATP and glutamine, but CPEC triphosphate induced sigmoidal kinetic plots. The Hill coefficient was calculated to be 3.2. PMID- 2910862 TI - The function of gamma-glutamylcysteine and bis-gamma-glutamylcystine reductase in Halobacterium halobium. AB - gamma-Glutamylcysteine and bis-gamma-glutamylcystine reductase appear to function in the halobacteria in a fashion analogous to GSH and glutathione reductase in other cells. Bis-gamma-glutamylcystine reductase (GCR), a NADPH-dependent dimer of Mr 122,000 recently purified to homogeneity from Halobacterium halobium (Sundquist, A.R., and Fahey, R.C. (1988) J. Bacteriol., 170, 3459-3467), was found to be highly specific for bis-gamma-glutamylcystine and to be present in cell extract at a level sufficient to maintain gamma-glutamylcysteine predominantly in its thiol form [( thiol]/[disulfide] approximately 50). Bis gamma-glutamylcystine reductase is similar to glutathione reductase in many respects; GCR demonstrated a FAD:subunit stoichiometry of 1, inhibition by heavy metal ions, and a pH optimum near neutrality. However, GCR exhibited no activity with GSSG and was most active at salt levels exceeding 2 M. A turnover number of 1,700 mumol min-1 mumol-1 FAD and apparent Km values of 0.8 mM for bis-gamma glutamylcystine and 0.29 mM for NADPH were determined for GCR. The effect of salt on the autoxidation rates of gamma-glutamylcysteine, GSH, and Cys was also studied. In the absence of added salt, Cys oxidized more rapidly than gamma glutamylcysteine, which in turn oxidized more rapidly than GSH. The presence of 4.3 M chloride (K+ and Na+) significantly slowed the autoxidation of all three thiols. The rate of autoxidation of gamma-glutamylcysteine in 4.3 M chloride proved slower than that of GSH in the absence of added chloride. Thus, gamma glutamylcysteine is at least as stable under halophilic conditions as GSH is under nonhalophilic conditions, explaining why halobacteria utilize gamma glutamylcysteine rather than GSH. PMID- 2910863 TI - Relative effectiveness of various ions on the solubility and crystal growth of lysozyme. AB - Crystallization conditions for hen egg white lysozyme in the presence of various ions were determined at pH 4.5 and 18 degrees C. The corresponding solubility curves show that the main effects are due to anions in the following order: SCN- greater than NO3- greater than Cl- greater than citrate2- greater than CH3COO- approximately H2PO4- greater than SO4(2-). This is in the reverse order of the lyotropic series of Hofmeister. As a consequence, SCN- precipitates and crystallizes lysozyme at low concentration, whereas sulfate is ineffective even at high concentrations. Crystals obtained with each salt were characterized by x ray diffraction. Lysozyme thiocyanate and nitrate crystals belong to the monoclinic system, whereas all the others have a tetragonal lattice. PMID- 2910864 TI - Prostaglandin and fatty acid omega- and (omega-1)-oxidation in rabbit lung. Acetylenic fatty acid mechanism-based inactivators as specific inhibitors. AB - Terminal acetylenic fatty acid mechanism-based inhibitors (Ortiz de Montellano, P. R., and Reich, N. O. (1984) J. Biol. Chem. 259, 4136-4141) were used as probes in determining the substrate specificity of rabbit lung cytochrome P-450 isozymes of pregnant animals in both microsomes and reconstituted systems. Lung microsomal and reconstituted P-450 form 5-catalyzed lauric acid omega- and (omega-1) hydroxylase activities were inhibited by a 12-carbon terminal acetylenic fatty acid, 11-dodecynoic acid (11-DDYA), and an 18-carbon terminal acetylenic fatty acid, 17-octadecynoic acid (17-ODYA). Rabbit lung microsomal lauric acid omega hydroxylase activity was more sensitive to inhibition by 11-DDYA than was (omega 1)-hydroxylase activity. In reconstituted systems containing purified P-450 form 5, both omega- and (omega-1)-hydroxylation of lauric acid were inhibited in parallel when either 11-DDYA or 17-ODYA was used. These data suggest the presence of at least two P-450 isozymes in rabbit lung microsomes capable of lauric acid omega-hydroxylation. This is the first report indicating the multiplicity of lauric acid hydroxylases in lung microsomes. Lung microsomal prostaglandin omega hydroxylation, mediated by the pregnancy-inducible P-450PG-omega (Williams, D. E., Hale, S. E., Okita, R. T., and Masters, B. S. S. (1984) J. Biol. Chem. 259, 14600-14608) was subject to inhibition by 17-ODYA only, whereas 11-DDYA acid was not an effective inhibitor of this hydroxylase. We have recently developed a new terminal acetylenic fatty acid, 12-hydroxy-16-heptadecynoic acid (12-HHDYA), that contains a hydroxyl group at the omega-6 position. We show that 12-HHDYA possesses a high degree of selectivity for the inactivation of rabbit lung microsomal prostaglandin omega-hydroxylase activity which cannot be obtained with the long chain acetylenic inhibitor, 17-ODYA. In addition, 12-HHDYA has no effect on lauric acid omega- or omega-1-hydroxylation or on benzphetamine N demethylation. The development of this new terminal acetylenic fatty acid inhibitor provides us with a useful tool with which to study the physiological role of prostaglandin omega-hydroxylation in the rabbit lung during pregnancy. PMID- 2910865 TI - A family of glycoinositol phospholipids from Leishmania major. Isolation, characterization, and antigenicity. AB - The glycolipids of the protozoan Leishmania major strain LRC-L119 belong to a class of glycoinositol phospholipids (GIPL) that show partial structural homology to the phosphatidylinositol-containing glycolipid membrane anchors of several eukaryotic proteins and the lipid moiety of L. major lipophosphoglycan. The GIPLs were the only glycolipids detected and were purified by octyl-Sepharose and thin layer chromatographies. Analysis of the native and dephosphorylated glycolipids (GIPLs 1-6) by gas chromatography-mass spectrometry revealed that the glycan moieties have between 4 and 10 saccharide residues and all contain mannose, galactose, and non-N-acetylated glucosamine. Some of the GIPLs also contain glucose (GIPL-6) and hexose monophosphate residues (GIPL 4-6). The presence of an inositol phospholipid moiety in all the GIPLs is indicated by the identification of 1 myo-inositol monophosphate residue/molecule and their susceptibility to phosphatidylinositol-specific phospholipase C. However, heterogeneity in the lipid moieties is indicated by differences in the compositional analysis and the behavior of the GIPLs on the thin layer chromatography after mild alkali hydrolysis or phospholipase A2 treatment. These results demonstrate that GIPLs 1 4 contain 1-alkyl-2-acylglycerol composed of saturated unbranched alkyl chains with carbon chain lengths of 18-26 and acyl chains of myristate, palmitate and stearate, whereas GIPL-5 and -6 contain lyso-alkylglycerol composed of mainly C24:0 and C26:0 alkyl chains. Analysis of the products of nitrous acid deamination demonstrates that these glycerolipids are present as alkylacylphosphatidylinositol (GIPLs 1-4) and 1-O-alkylglycerophosphoinositol (GIPL-5 and -6), respectively. GIPL-2 and -3 are labeled on the surface of living promastigotes with galactose oxidase/NaB[3H]4. These GIPLs also react with three monoclonal antibodies that recognize the surface of promastigotes and amastigotes of L. major and other Leishmania spp. PMID- 2910866 TI - Decreasing extracellular Na+ concentration triggers inositol polyphosphate production and Ca2+ mobilization. AB - Removing extracellular Na+ (Na+o) evoked a large increase in cytosolic free Ca2+ concentration ([Ca2+]i in human skin fibroblasts. Decreasing [Na+]o from 120 to 14 mM caused the half-maximal peak increase in [Ca2+]i. Removing Na+o strongly stimulated 45Ca2+ efflux and decreased total cell Ca2+ by about 40%. Bradykinin caused changes in [Ca2+]i, total Ca2+, and 45Ca2+ fluxes similar to those evoked by removing Na+o. Prior stimulation of the cells with bradykinin prevented Na+o removal from increasing [Ca2+]i and vice versa. Na+o removal rapidly increased [3H]inositol polyphosphate production. Loading the cells with Na+ had no effect on the increase in 45Ca2+ efflux produced by Na+o removal. Therefore, decreasing [Na+]o probably stimulates a "receptor(s)" which is sensitive to extracellular, not intracellular, Na+. Removing Na+o also mobilized intracellular Ca2+ in smooth muscle and endothelial cells cultured from human umbilical and dog coronary arteries, respectively. PMID- 2910867 TI - Biochemistry of terminal deoxynucleotidyltransferase. Identification and unity of ribo- and deoxyribonucleoside triphosphate binding site in terminal deoxynucleotidyltransferase. AB - Terminal deoxynucleotidyltransferase is the only DNA polymerase that is strongly inhibited in the presence of ATP. We have labeled calf terminal deoxynucleotidyltransferase with [32P]ATP in order to identify its binding site in terminal deoxynucleotidyltransferase. The specificity of ATP cross-linking to terminal deoxynucleotidyltransferase is shown by the competitive inhibition of the overall cross-linking reaction by deoxynucleoside triphosphates, as well as the ATP analogs Ap4A and Ap5A. Tryptic peptide mapping of [32P]ATP-labeled enzyme revealed a peptide fraction that contained the majority of cross-linked ATP. The properties, chromatographic characteristics, amino acid composition, and sequence analysis of this peptide fraction were identical with those found associated with dTTP cross-linked terminal deoxynucleotidyl-transferase peptide (Pandey, V. N., and Modak, M. J. (1988a). J. Biol. Chem. 263, 3744-3751). The involvement of the same 2 cysteine residues in the crosslinking of both nucleotides further confirmed the unity of the ATP and dTTP binding domain that contains residues 224 237 in the primary amino acid sequence of calf terminal deoxynucleotidyltransferase. PMID- 2910868 TI - Structures of neutral O-linked polylactosaminoglycans on human skim milk mucins. A novel type of linearly extended poly-N-acetyllactosamine backbones with Gal beta(1-4)GlcNAc beta(1-6) repeating units. AB - O-Linked oligosaccharides were isolated from human skim milk mucins and from mucin-derived glycopeptides by reductive beta-elimination. The released alditols were fractionated by DEAE-Sephadex chromatography and purified by high performance liquid chromatography on primary amine bonded phase. The structures of the major neutral oligosaccharide alditols could be established by fast atom bombardment and electron impact mass spectrometry, combined with methylation analysis, 500-MHz 1H nuclear magnetic resonance spectroscopy, and endo-beta galactosidase (from Bacteroides fragilis, EC 3.2.1.103) digestion (where n = 0 3): (formula; see text) Major O-glycosidically linked oligosaccharides on skim milk mucins are of the Gal beta(1-3)[GlcNAc beta(1-6)] GalNAc core type 2 and exhibit linearly extended backbone chains of the poly N-acetyllactosamine type comprizing up to at least four repeating units, which are linked by the hitherto unknown sequence GlcNAc-beta(1-6) Gal rather than GlcNAc beta(1-3)Gal. A considerable portion of neutral alditols is represented by branched isomers of the linear species, which are distinguished by their content of 3,6-disubstituted galactose and their partial resistance to endo-beta-galactosidase digestion. PMID- 2910869 TI - Kinetics of activation of phospholipase C by P2Y purinergic receptor agonists and guanine nucleotides. AB - Membranes prepared from [3H]inositol-labeled turkey erythrocytes express a phospholipase C that is markedly stimulated by stable analogs of GTP (Harden, T. K., Stephens, L., Hawkins, P. T., and Downes, C. P. (1987) J. Biol. Chem. 262, 9057-9061). We now report that P2-purinergic receptor-mediated regulation of the enzyme occurs in the membrane preparation. The order of potency of a series of ATP and ADP analogs for stimulation of inositol phosphate formation, i.e. 2 methylthioadenosine 5'-triphosphate (2MeSATP) greater than adenosine 5'-O-(2 thiodiphosphate) greater than adenosine 5'-O-(3-thiotriphosphate) greater than ATP greater than 5'-adenylyl imidodiphosphate approximately ADP greater than alpha, beta-methyleneadenosine 5'-triphosphate greater than beta, gamma methyleneadenosine 5'-triphosphate, was consistent with that for the P2Y purinergic receptor subtype. Agonist-stimulated effects were completely dependent on the presence of guanine nucleotide. Activation of phospholipase C by guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) occurred with a considerable time lag. The rate of activation followed first order kinetics and was markedly increased by increasing concentrations of a P2Y receptor agonist; in contrast, the rate of activation at a fixed agonist concentration was independent of guanine nucleotide concentration. Addition of guanosine 5'-O-(2-thiodiphosphate) (GDP beta S) prior to addition of agonist and GTP, 5'-guanylyl imidodiphosphate (Gpp(NH)p), or GTP gamma S blocked in a concentration-dependent manner the stimulatory effect of guanine nucleotide. GDP beta S, added subsequent to preactivation of membranes with 2MeSATP and GTP gamma S or Gpp(NH)p had only small inhibitory effects on the rate of inositol phosphate production observed over the subsequent 10 min. In contrast, addition of GDP beta S to GTP-preactivated membranes resulted in a rapid return of enzyme activity to the basal state within 60 s. Taken together, the data are consistent with the idea that P2Y receptor activation increases the rate of exchange of GTP and GTP analogs for GDP on the relevant guanine nucleotide regulatory protein. Once the active enzymic species is formed, hydrolysis of guanine nucleotide reverts the enzyme to the inactive state. PMID- 2910870 TI - Characterization of tyrosylprotein sulfotransferase from rat liver and other tissues. AB - The sulfoconjugation of tyrosyl residues is a widespread post-translational modification of biologically active peptides and proteins. In this paper we describe the characterization of a rat liver tyrosylprotein sulfotransferase that is capable of catalyzing the transfer of a sulfate moiety from 3' phosphoadenosine 5'-phosphosulfate (PAPS) to the synthetic polymer, poly (Glu6,Ala3,Tyr1) (EAY; Mr 47,000) using a simple filter paper assay. Following sucrose density gradient centrifugation and comparison with known subcellular marker enzyme activities, rat liver tyrosylprotein sulfotransferase activity was shown to have a distribution similar to the Golgi enzyme, galactosyltransferase. Using the enriched Golgi preparation, rat liver tyrosylprotein sulfotransferase displayed a pH optimum of 6.7 and required the presence of 20 mM Mn2+ for maximal activity. Co2+ (20 mM) was able to produce 26% of the maximal stimulation observed with Mn2+, whereas other metal ions, such as Mg2+, Ca2+, and Co2+, were not effective in stimulating tyrosylprotein sulfotransferase activity. Whereas tyrosylprotein sulfotransferase activity was observed in the native membrane bound state, EAY sulfation was maximally enhanced 3-fold when assayed in the presence of Lubrol Px. Under the optimal conditions for assaying the sulfation of EAY by a rat liver enriched Golgi fraction, significant degradation of the sulfate donor, PAPS, was observed. The addition of both NaF and 5'-AMP to the incubation mixture was found to effectively prevent PAPS degradation and increase the amount of product formed in the assay by 10-fold. Using the optimized conditions for the sulfation of EAY by rat liver tyrosylprotein sulfotransferase, membrane-bound sulfotransferase activity was also observed in the crude microsomal pellets of a variety of rat tissues, including lung, pituitary, and cerebellum, as well as in livers from different species. PMID- 2910871 TI - Mechanism of vitamin A movement between rod outer segments, interphotoreceptor retinoid-binding protein, and liposomes. AB - Vitamin A movement between rod outer segment (ROS) membranes, interphotoreceptor retinoid-binding protein (IRBP), and liposomes was examined by two different methods. Equilibrium exchange of all-trans-retinol was followed by assessing the transfer of [3H]retinol from liposomes to ROS membranes as compared to a nontransferable marker, [14C]triolein. In the absence of IRBP, a rapid, spontaneous transfer of [3H] retinol to the ROS membranes occurred. In the presence of 2 microM IRBP, retinol transfer decreased by approximately one-half, whereas a similar concentration of bovine serum albumin had no effect on this spontaneous transfer. Kinetics of retinol transfer between single unilamellar vesicles were determined by the method of fluorescence energy transfer. The first order rate constant for this transfer was 0.85 s-1 at 22 degrees C at either pH 7.4 or pH 2.8. This rate was not affected by varying the concentration of acceptor vesicles 50-fold or by varying their concentration 10-fold at a constant ratio of donor-to-acceptor vesicles. The presence of IRBP as an additional acceptor did not change the rate. The transfer was temperature-dependent with an activation energy of 7.8 kcal/mol. The transfer rate appeared to be an increasing exponential function of ionic strength since high concentrations of NaCl decreased the transfer rate significantly. The transfer rate of retinol from IRBP to single unilamellar vesicles also followed first order kinetics with a rate constant of 0.11 s-1 at 22 degrees C, which was approximately 8 times slower than that of transfer between vesicles. We conclude that the transfer of all-trans retinol between liposomes and membranes can be accomplished rapidly via the aqueous phase, and that IRBP retards rather than facilitates this transfer process. PMID- 2910872 TI - Cetacean relaxin. Isolation and sequence of relaxins from Balaenoptera acutorostrata and Balaenoptera edeni. AB - The tendency toward extremely high variability among relaxins derived from purportedly closely related species has come to an abrupt end with the discovery of quasi-porcine relaxin in the minke whale (Balaenoptera acutorostrata) and the Bryde's whale (Balaenoptera edeni). An aqueous abstract of the corpora lutea of the two baleen whales contained significant amounts of relaxin-like activity as determined by a mouse bioassay and by cross-reactivity with anti-pig relaxin antibodies. The activity could be isolated and purified to homogeneity. Sequence analysis revealed that both whale relaxins differed from each other by about 3 residues, whereas the relaxin of B. edeni differed at only one position from that of pig relaxin. The similarity appears to include even the chain length heterogeneity observed at the C-terminal end of the B chain in porcine relaxin which is produced by a peculiar mode of connecting peptide removal from the pro hormone. This finding may well represent one of the better documented challenges to the current paradigm of molecular evolution. PMID- 2910873 TI - The molecular mechanism of the neutral-to-base transition of human serum albumin. Acid/base titration and proton nuclear magnetic resonance studies on a large peptic and a large tryptic fragment of albumin. AB - In order to obtain a better understanding of the neutral-to-base (N-B) transition of human serum albumin, we performed acid/base titration experiments and 500-MHz 1H NMR experiments on albumin and on a large peptic (residues 1-387) and large tryptic (residues 198-585) fragment of albumin. The acid/base titration experiments revealed that Ca2+ ions induce a downward pK shift of several histidine residues of the peptic (P46) fragment and of albumin. By contrast, Ca2+ has very little influence on the pK of histidine residues of the tryptic (T45) fragment. In albumin, the pH-dependent His C-2 proton resonances, observed with 1H NMR experiments, have been allotted the numbers 1-17. It proved possible to locate these resonances in the P46 and the T45 fragments. A correspondence was found between the number of histidines detected by the acid/base titration and by the 1H NMR experiments. The results of the experiments lead us to conclude that in domain 1 at least the histidines corresponding to the His C-2 proton resonances 1-5 play a dominant role in the N-B transition. The Cu2+-binding histidine residue 3 (resonance 8) of the albumin molecule is not involved in the N-B transition. In addition, we were able to assign His C-2 proton resonance 9 to histidine 464 of the albumin molecule. The role of the N-B transition in the transport and cellular uptake mechanisms of endogenous and exogenous compounds is discussed. PMID- 2910874 TI - Intracellular compartmentation of deoxycytidine nucleotide pools in S phase mouse 3T3 fibroblasts. AB - We labeled mouse 3T3 fibroblasts, synchronized in G0 or S phase, from [3H]cytidine or [3H]deoxycytidine and measured the flow of isotope into and through deoxycytidine nucleotide pools, including the two deoxyliponucleotides dCDP choline and dCDP ethanolamine. Compared to G0 cells, S phase cells had much larger pools with a 20-40-fold faster turnover. The dCTP pool of S phase cells during steady state conditions attained a 6-fold higher specific activity than the pool of G0 cells when labeled from cytidine but a 10-fold lower specific activity when labeled from deoxycytidine. The dCTP pool of G0 cells showed a slow but measurable turnover indicating a limited amount of de novo synthesis also in resting cells. The labeling pattern of dCTP and deoxyliponucleotides of G0 cells was compatible with a simple precursor-product relationship. In S phase cells, however, dCDP choline had a 4-6 times higher specific activity during steady state conditions than dCTP and dCMP when the cells were labeled with [3H]deoxycytidine. We suggest that 3T3 cells contain two distinct intracellular dCTP pools, one labeled preferentially from cytidine and used for DNA replication, the other labeled from deoxycytidine and used for deoxyliponucleotide synthesis. We speculate that the latter pool during S phase may be temporarily sequestered in the cell's membrane fraction before equilibration with the much larger dCTP pool originating in S phase cells from the reduction of CDP. PMID- 2910875 TI - Mapping replicational sites in the eucaryotic cell nucleus. AB - We have used fluorescent microscopy to map DNA replication sites in the interphase cell nucleus after incorporation of biotinylated dUTP into permeabilized PtK-1 kangaroo kidney or 3T3 mouse fibroblast cells. Discrete replication granules were found distributed throughout the nuclear interior and along the periphery. Three distinct patterns of replication sites in relationship to chromatin domains in the cell nucleus and the period of S phase were detected and termed type I (early to mid S), type II (mid to late S) and type III (late S). Similar patterns were seen with in vivo replicated DNA using antibodies to 5 bromodeoxyuridine. Extraction of the permeabilized cells with DNase I and 0.2 M ammonium sulfate revealed a striking maintenance of these replication granules and their distinct intranuclear arrangements with the remaining nuclear matrix structures despite the removal of greater than 90% of the total nuclear DNA. The in situ prepared nuclear matrix structures also incorporated biotinylated dUTP into replication granules that were indistinguishable from those detected within the intact nucleus. PMID- 2910876 TI - Analysis of the calcium-modulated proteins, S100 and calmodulin, and their target proteins during C6 glioma cell differentiation. AB - We have analyzed the levels, subcellular distribution, and target proteins of two calcium-modulated proteins, S100 and calmodulin, in differentiated and undifferentiated rat C6 glioma cells. Undifferentiated and differentiated C6 cells express primarily the S100 beta polypeptide, and the S100 beta levels are four-fold higher in differentiated compared to undifferentiated cells. Double fluorescent labeling studies of undifferentiated cells demonstrated that S100 beta staining localized to a small region of the perinuclear cytoplasm and colocalized with the microtubule organizing center and Golgi apparatus. Analysis of differentiated C6 cells demonstrated that S100 beta distribution and S100 beta binding protein profile changed significantly upon differentiation. In addition, the brain-specific isozyme of one S100-binding protein, fructose-1,6-bisphosphate aldolase C, can be detected in differentiated but not undifferentiated C6 cells. While changes in the subcellular distribution of calmodulin were not observed during differentiation, calmodulin levels and calmodulin-binding protein profiles did change. Altogether these data suggest that S100 beta and calmodulin regulate different processes in glial cells and that the regulation of the expression, subcellular distribution, and target proteins of S100 beta and calmodulin during differentiation is a complex process which involves multiple mechanisms. PMID- 2910877 TI - Activation of the cell wall degrading protease, lysin, during sexual signalling in Chlamydomonas: the enzyme is stored as an inactive, higher relative molecular mass precursor in the periplasm. AB - During the mating reaction in Chlamydomonas reinhardtii mating type plus and mating type minus gametes adhere to each other via adhesion molecules on their flagellar surfaces. This adhesive interaction induces a sexual signal leading to release of a cell wall degrading enzyme, lysin, that causes wall release and degradation. In this article, we describe the preparation of a polyclonal antibody against the 60,000-Mr lysin polypeptide excised from SDS-PAGE gels. After absorption of the IgG with cell walls to remove antibodies against a carbohydrate epitope common to several Chlamydomonas glycoproteins, the immune IgG reacted with the 60,000-Mr polypeptide, and a 47,000-Mr species that we show here was immunologically cross-reactive with the 60,000-Mr molecule. By use of several fractionation methods including ion exchange and molecular sieve chromatography, sucrose gradient centrifugation, and affinity chromatography, we showed that the 60,000-Mr antigen copurified with lysin activity, thereby demonstrating that the antibody was indeed directed against the enzyme. Immunoblot experiments on suspensions of nonmating and mating gametes showed that the 60,000-Mr antigen was missing in the nonmating gametes. Instead, they contained a 62,000-Mr antigen that was not present in suspensions of mating gametes that had undergone sexual signalling. Furthermore, nonmating gametes whose walls were removed with exogenously added lysin did not contain either form of the antigen. We also found that the 62,000-Mr form of the antigen, which could be released from gametes by freeze-thawing, did not have wall degrading activity. These results indicate that lysin in gametes is stored in the periplasm as a higher relative molecular mass, inactive precursor and also that sexual signalling induces conversion of this molecule to a lower relative molecular mass, active enzyme. This may be a novel example of processing of an extracellular protease induced by cell contact. PMID- 2910878 TI - A unique cytoskeleton associated with crawling in the amoeboid sperm of the nematode, Ascaris suum. AB - Nematode sperm extend pseudopods and pull themselves over substrates. They lack an axoneme or the actin and myosins of other types of motile cells, but their pseudopods contain abundant major sperm protein (MSP), a family of 14-kD polypeptides found exclusively in male gametes. Using high voltage electron microscopy, a unique cytoskeleton was discovered in the pseudopod of in vitro activated, crawling sperm of the pig intestinal nematode Ascaris suum. It consists of 5-10-nm fuzzy fibers organized into 150-250-nm-thick fiber complexes, which connect to each of the moving pseudopodial membrane projections, villipodia, which in turn make contact with the substrate. Individual fibers in a complex splay out radially from its axis in all directions. The centripetal ends intercalate with fibers from other complexes or terminate in a thickened layer just beneath the pseudopod membrane. Monoclonal antibodies directed against MSP heavily label the fiber complexes as well as individual pseudopodial filaments throughout their length. This represents the first evidence that MSP may be the major filament protein in the Ascaris sperm cytoskeleton. The large fiber complexes can be seen clearly in the pseudopods of live, crawling sperm by computer-enhanced video, differential-interference contrast microscopy, forming with the villipodia at the leading edge of the sperm pseudopod. Even before the pseudopod attaches, the entire cytoskeleton and villipodia move continuously rearwards in unison toward the cell body. During crawling, complexes and villipodia in the pseudopod recede at the same speed as the spermatozoon moves forward, both disappearing at the pseudopod-cell body junction. Sections at this region of high membrane turnover reveal a band of densely packed smooth vesicles with round and tubular profiles, some of which are associated with the pseudopod plasma membrane. The exceptional anatomy, biochemistry, and phenomenology of Ascaris sperm locomotion permit direct study of the involvement of the cytoskeleton in amoeboid motility. PMID- 2910880 TI - Localization of basic fibroblast growth factor to the developing capillaries of the bovine retina. AB - The basic fibroblast growth factor (FGF) is a potent mitogen that has vascular endothelium as one of its principle target cells. Recent work has provided both the complete amino acid sequence of basic FGF and the nucleotide sequence of the genes for both human and bovine basic FGF. Although capillary endothelial cells have been shown to produce basic FGF in vitro and to deposit basic FGF in their extracellular matrix in vitro as well, no direct evidence yet exists for the distribution of basic FGF in vivo. Antipeptide antibodies were prepared against a 15-amino-acid sequence from the amino terminus of basic FGF in order to avoid cross-reactivity with acidic FGF, a protein with 55% overall homology to basic FGF. After affinity purification, these antisera were used to localize the basic fibroblast growth factor in the fetal and adult bovine retina. Immunoreactive material was found in capillaries of the inner nuclear layer, a capillary network undergoing development during the third trimester in the fetal bovine eye. Although the resolution of the technique does not permit a unique assignment of cellular localization, the presence of stain immediately adjacent to the lumen of capillaries suggests that capillary endothelial cells may produce the basic fibroblast growth factor in vivo during vascular development. PMID- 2910881 TI - Decreased susceptibility of cultured smooth muscle cells from SHR rats to growth inhibition by heparin. AB - Smooth muscle cell proliferation is regulated through the coordinated action of growth inhibitors and growth factors/mitogens; a specific heparin-epidermal growth factor (EGF) complementation has been proposed (Reilly et al., 1987, J. Cell. Physiol., 131:149-157). In culture, vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) proliferate more rapidly than VSMC from control Wistar Kyoto rats (WKY). We observed that, compared with WKY-derived VSMC, cells from SHR were markedly less susceptible to growth inhibition both by heparin and its homopolysaccharide analogue pentosan polysulphate (PPS). SHR derived VSMC exhibited a reduced capacity for binding of [3H]heparin to specific extracellular surface receptors, whereas affinities for heparin were comparable between both VSMC isolates. The early (0-2 hr at 37 degrees C) kinetics of internalization did not differ between SHR- and WKY-derived VSMC, but both internalized equivalent proportions (approximately 10%) of initially surface bound heparin. VSMC from SHR exhibited a greater capacity, without a changed affinity, for [I125]EGF binding than VSMC from WKY. Pre-exposure of VSMC to heparin or PPS decreased, in a time-dependent manner, the EGF binding capacity for both SHR and WKY (by 40-50% after 72 hr). However, in absolute terms, the EGF binding capacity of VSMC from SHR exposed to heparinoids was similar to that of nonexposed VSMC from WKY. PMID- 2910879 TI - Primary structure of the brain alpha-spectrin. AB - We have determined the nucleotide sequence coding for the chicken brain alpha spectrin. It is derived both from the cDNA and genomic sequences, comprises the entire coding frame, 5' and 3' untranslated sequences, and terminates in the poly(A)-tail. The deduced amino acid sequence was used to map the domain structure of the protein. The alpha-chain of brain spectrin contains 22 segments of which 20 correspond to the repeat of the human erythrocyte spectrin (Speicher, D. W., and V. T. Marchesi. 1984. Nature (Lond.). 311:177-180.), typically made of 106 residues. These homologous segments probably account for the flexible, rod like structure of spectrin. Secondary structure prediction suggests predominantly alpha-helical structure for the entire chain. Parts of the primary structure are excluded from the repetitive pattern and they reside in the middle part of the sequence and in its COOH terminus. Search for homology in other proteins showed the presence of the following distinct structures in these nonrepetitive regions: (a) the COOH-terminal part of the molecule that shows homology with alpha actinin, (b) two typical EF-hand (i.e., Ca2+-binding) structures in this region, (c) a sequence close to the EF-hand that fulfills the criteria for a calmodulin binding site, and (d) a domain in the middle of the sequence that is homologous to a NH2-terminal segment of several src-tyrosine kinases and to a domain of phospholipase C. These regions are good candidates to carry some established as well as some yet unestablished functions of spectrin. Comparative analysis showed that alpha-spectrin is well conserved across the species boundaries from Xenopus to man, and that the human erythrocyte alpha-spectrin is divergent from the other spectrins. PMID- 2910882 TI - Growth-related changes of oxygen consumption rates of tumor cells grown in vitro and in vivo. AB - Growth-related changes of oxygen consumption rates of tumor cells, grown in vitro or in vivo, were investigated. For in vitro investigations, L929 and DS carcinosarcoma cells were cultured in artificial media. For in vivo studies, DS carcinosarcoma cells were implanted into the abdominal cavity of Sprague-Dawley rats (ascites tumor, containing malignant cells, leukocytes, lymphocytes, and macrophages). Oxygen uptake was measured photometrically. Parameters of the extracellular medium judged to possibly influence the respiratory activity of tumor cells were monitored at different growth stages (glucose, lactate, and amino acid levels, oxygen and carbon dioxide partial pressures, and pH values). The results obtained clearly show that the oxygen uptake of tumor cells grown in vitro decreased as quiescence developed. In contrast, the respiratory activity of in vivo DS-carcinosarcoma ascites cells increased as tumor growth reached plateau phase. The differences observed cannot be attributed solely to changes of the environmental conditions monitored. It is likely that an increased respiration rate of activated host cells might profoundly contribute to the elevation of the respiratory capacity of DS-carcinosarcoma ascites tumors grown in vivo. These data provide evidence that solid tumors in vivo can increase their O2 uptake at an enhanced O2 availability not only due to an enlarged tumor volume with adequate O2 supply but also due to an elevation of the respiratory activity of different cell populations within a tumor. PMID- 2910883 TI - Butyric acid causes morphological changes in cultured chondrocytes through alterations in the extracellular matrix. AB - Butyric acid induces characteristic changes in the morphology of chick embryo chondrocytes. Chick embryo chondrocytes when cultured in the absence of butyrate exhibit a spherical morphology and synthesize cartilage-specific chondroitin sulfate proteoglycan (CSPG). When these cultures are initiated and maintained in the presence of butyric acid, chondrocytes exhibit a mesenchymal morphology, a 90% reduction in the synthesis of CSPG, and a 75% reduction in DNA synthesis. The reduced synthesis of CSPG and DNA was shown not to be dependent on the morphological change. Chondrocytes require CSPG in order to express a spherical morphology, since including chondroitinase ABC in the culture media caused the cells to spread. In addition, the treatment of chondrocytes with purified CSPG prior to culture in media containing butyric acid resulted in spherical cells. The butyrate-induced spreading was shown to require either serum or fibronectin and could be prevented with antiserum against chick cell-surface fibronectin (cFn). Cell-surface fibronectin, which was present on both spherical and flattened chondrocytes, organized into fibrils beneath cells which spread. Increased fibronectin synthesis was not responsible for the butyrate-induced morphological change. From this evidence, it is concluded that the mechanism by which butyrate alters the morphology of these cells in culture involves inhibiting CSPG synthesis, thus preventing CSPG accumulation in the extracellular matrix (ECM). The absence of CSPG in the ECM allows fibronectin to mediate spreading of chondrocytes in culture. PMID- 2910884 TI - Interaction of heparin with human basic fibroblast growth factor: protection of the angiogenic protein from proteolytic degradation by a glycosaminoglycan. AB - Fibroblast growth factors (FGF) are a family of heparin-binding angiogenic polypeptide mitogens. In the presence of heparin, recombinant human basic fibroblast growth factor (bFGF) is fully protected from tryptic digestion and partially protected from chymotryptic digestion. Complete protection of bFGF by heparin is achieved at ratios of growth factor:heparin of approximately 10 or less (w/w). The protection requires bioactive bFGF because inactivated bFGF is rapidly degraded by trypsin or chymotrypsin in the presence of heparin. The bFGF heparin interaction forms hydrophobic complexes which become insoluble in aqueous buffers at bFGF:heparin ratios of 8 to 10 (w/w). The heparin was found to bind up to a tenfold excess of bFGF on a weight basis. bFGF in the presence of heparin is as active as bFGF alone in inducing 3H-thymidine incorporation into Swiss 3T3 fibroblast DNA. PMID- 2910885 TI - Stochastic model for mast cell proliferation in culture of murine peritoneal cells. AB - We recently identified two types of mast cell colonies derived from murine peritoneal cells: type 1 and type 2. Type 1 mast cell colonies consisted of berberine sulfate(+)- safranin(+) connective tissue-type mast cells (CTMC) and were derived from mature CTMC in the heaviest fraction obtained by Percoll density gradient centrifugation. In contrast, type 2 mast cell colonies consisted of alcian blue(+)- berberine sulfate(-)- safranin(-) mucosal mast cells (MMC) and were derived from immature progenitors in low density fractions. We replated a total of 60 type 1 and 60 type 2 mast cell colonies and examined their capability for producing secondary colonies. Although all of the primary colonies yielded secondary colonies, the replating efficiencies of individual colonies varied over a wide range. Cumulative distributions of secondary colonies from both type 1 and type 2 primary colonies could be fitted well by gamma distributions obtained by computer simulation. These findings are in agreement with the stochastic model for CTMC- and MMC proliferation. Cytological analyses of secondary colonies from primary type 1 colonies revealed heterogeneous distributions of alcian blue(+)- safranin(-)- berberine sulfate(-) mast cells, suggesting that transdifferentiation from mature CTMC to safranin(-)- berberine sulfate(-) mast cells is also governed by stochastic mechanisms. PMID- 2910886 TI - Altered formation of DNA replication intermediates in cells growing in different culture conditions. AB - In human melanoma cells one can detect two discrete DNA replication intermediates, 10-kb DNA intermediates and Okakzaki fragments. Both intermediates are seen when cells are rapidly growing in medium supplemented with fetal calf serum. When the medium is supplemented with newborn calf serum, one can detect Okakzaki fragments but not 10-kb DNA intermediates. In contrast we do not detect changes in the replicon sizes in the two media. PMID- 2910887 TI - Superoxide dismutase activities of differentiating clones from an immortal cell line. AB - We have studied superoxide dismutase (SOD) levels in the X-REF-23 rat embryo fibroblast cell line. X-REF-23 is an immortal cell line that maintains a nontransformed phenotype throughout its known lifespan. Low-passage X-REF-23 cells undergo spontaneous differentiation into muscle and adipose cells, while high-passage X-REF-23 cells undergo little or no differentiation. SOD activities were measured in subclones of X-REF-23, which differentiate into muscle (AMC subclone) or adipose (AMB-J) cells, as well as the parental nondifferentiating X REF-23 cells. Total SOD activity increased in all three cell lines with time in culture. Cu-ZnSOD was induced in the AMB-J and the X-REF-23 cells with time in culture, whereas the AMC cells showed no induction. MnSOD activity was induced during the time period in which differentiation occurred in the two differentiating clones. In contrast, MnSOD was not induced in this time period in the nondifferentiating X-REF-23 cell line. However, MnSOD activity was induced in the latter cell line at a much later time. Levels of immunoreactive MnSOD correlated quite well with MnSOD activity in all three cell lines. The nondifferentiating X-REF-23 cells, but not the two differentiating cells lines, showed a large increase in cell organelles with time in culture. In particular, an increase in very small mitochondria was observed; these mitochondria often showed evidence of disorganization. PMID- 2910888 TI - Plasma membrane lipid organization and the adherence of differentiating lymphocytes to macrophages. AB - Changes in the packing of phospholipids in the plasma membrane of lymphocytes occur during differentiation within primary and secondary lymphoid organs. As they differentiate, lymphocytes interact with a variety of reticuloendothelial cells, including macrophages. To investigate a possible relation between these two phenomena, the strength of the interactions between lymphocytes and macrophages was measured in vitro as a function of the tightness of packing of phospholipids on the lymphocyte surface. Strength of adherence was measured by the ability of lymphocytes to remain adherent to macrophages when subjected to increasing centrifugal forces. Phospholipid packing was assessed using the fluorescent lipophilic probe merocyanine 540 (MC540), which preferentially binds to bilayers in which the lipids are more loosely packed. Three subpopulations of murine thymocytes were resolved with respect to strength of adherence to peritoneal or thymic macrophages. To determine whether these subpopulations corresponded with the three classes of cells distinguishable by MC540 fluorescence, populations enriched for staining or non-staining cells, and cells sorted on the basis of MC540 fluorescence intensity, were examined. The least fluorescent cells were the least strongly adherent; the most fluorescent cells were the most strongly adherent; and cells of intermediate fluorescence had intermediate adherence. When splenic lymphocytes were examined with respect to adherence to peritoneal or splenic macrophages, similar patterns of fluorescence and adherence were seen. These results suggest that the organization of the plasma membrane lipid bilayer of lymphocytes may be involved in their interactions with macrophages during primary and secondary differentiation. The adherence signal for lymphocytes thus may be similar to that proposed for other blood cells. PMID- 2910889 TI - Immunodetection and quantitation of the two forms of transforming growth factor beta (TGF-beta 1 and TGF-beta 2) secreted by cells in culture. AB - Transforming growth factor beta (TGF-beta), a potent modulator of cell growth, differentiation, and the expression of extracellular matrix components in a variety of cell types, exists as two distinct homodimers (TGF-beta 1 and TGF-beta 2), sharing 71% sequence homology. Radioreceptor and previously described radioimmunological assays using rabbit antibodies have not been able to distinguish between these two forms. We have developed antisera in turkeys against native TGF-beta 1 and TGF-beta 2, each of which specifically blocks both the receptor binding and biological activity of each of these peptides. With these immunological reagents we describe sensitive and specific immunological assays for TGF-beta 1 and TGF-beta 2 in complex biological fluids. Using these assays we show that both TGF-beta 1 and TGF-beta 2 are secreted by a variety of cultured cells, but that some cells secrete predominantly either TGF-beta 1 or TGF-beta 2 while others secrete both peptides in nearly equal amounts. Our results demonstrate that the expression of each of the two forms of TGF-beta is independently regulated. PMID- 2910890 TI - L-ascorbic acid 2-phosphate stimulates collagen accumulation, cell proliferation, and formation of a three-dimensional tissuelike substance by skin fibroblasts. AB - Proliferation of human skin fibroblasts was stimulated significantly by the presence of L-ascorbic acid 2-phosphate (Asc 2-P). The presence of Asc 2-P (0.1 1.0 mM) in the culture medium for 3 weeks enhanced the relative rate of collagen synthesis to total protein synthesis 2-fold as well as cell growth 4-fold. Coexistence of L-azetidine 2-carboxylic acid (AzC), an inhibitor of collagen synthesis, attenuated both effects of Asc 2-P in a dose-dependent manner. Supplementation of the medium with Asc 2-P also accelerated procollagen processing to collagen and deposition of collagen in the cell layer. Among the acidic glycosaminoglycans (GAG), another major component of extracellular matrix (ECM), deposition of sulfated forms was increased by the additive. Electron microscopic observations showed multilayered, rough endoplasmic reticulum-rich cells surrounded by dense ECM. These results indicate that Asc 2-P is useful in culture systems as a long-acting vitamin C derivative and also that it promotes reorganization of a three-dimensional tissuelike substance from skin fibroblasts in culture by stimulating collagen accumulation in the fibroblasts. PMID- 2910891 TI - Measurement of blood-brain hexose transport with dynamic PET: comparison of [18F]2-fluoro-2-deoxyglucose and [11C]O-methylglucose. AB - Blood-to-tissue transport of [18F]2-fluoro-2-deoxyglucose (FDG) and [11C]O methylglucose (CMG) was compared by dynamic positron emission tomography in four patients with recent ischemic infarcts and in three patients with intracerebral tumors. Local blood volume, tracer transport from tissue to blood, and FDG phosphorylation rates were also determined. A regional analysis of parametric images showed a close correlation of FDG and CMG transport rate constants in pathological tissue. Transport rates of FDG and CMG showed correspondingly less asymmetric remote effects than FDG phosphorylation rates. Transport rate constants were consistently higher for FDG than for CMG in pathological and normal tissue, in accordance with the higher affinity of carrier enzymes to FDG. There was a significant correlation between fitted regional blood volume values and correspondence of average absolute values with both tracers. It is concluded that dynamic FDG PET for measurement of cerebral glucose metabolism is also useful to measure alterations of hexose transport and local blood volume in pathological tissue. PMID- 2910892 TI - Hypothesis: vasoconstriction contributes to amaurosis fugax. AB - Platelets play a critical role in the pathophysiology of amaurosis fugax. Emboli to retinal vessels apparently produce amaurosis but, in addition, we propose that augmented vasoconstrictor responses and vasospasm may contribute to amaurosis. In this study we tested the hypothesis that constrictor responses of retinal vessels to serotonin, which is released when platelets aggregate, are potentiated in experimental atherosclerosis. Blood flow to the retina was measured in normal and atherosclerotic cynomolgus monkeys. In normal monkeys, infusion of serotonin did not alter flow to the retina. In atherosclerotic monkeys, infusion of serotonin reduced retinal blood flow (in milliliters per minute per 100 g) from 66 +/- 7 (mean +/- SE) to 5 +/- 2. Infusion of serotonin in atherosclerotic monkeys abolished the retinal response to light. Thus, atherosclerosis greatly potentiates constrictor responses to serotonin in the retinal circulation and produces a profound but reversible impairment of retinal function. We propose that altered responses to vasoactive substances that are released by platelets may contribute to the pathogenesis of amaurosis fugax. PMID- 2910893 TI - Effects of traumatic brain injury on regional cerebral blood flow in rats as measured with radiolabeled microspheres. AB - To clarify the effect of experimental brain injury on regional CBF (rCBF), repeated rCBF measurements were performed using radiolabeled microspheres in rats subjected to fluid-percussion traumatic brain injury. Three consecutive microsphere injections in six uninjured control rats substantiated that the procedure induces no significant changes in hemodynamic variables or rCBF. Animals were subjected to left parietal fluid-percussion brain injury of moderate severity (2.1-2.4 atm) and rCBF values were determined (a) prior to injury and 15 min and 1 h following injury (n = 7); and (b) prior to injury and 30 min and 2 h following injury (n = 7). At 15 min post injury, there was a profound reduction of rCBF in all brain regions studied (p less than 0.01). Although rCBF in the hindbrain had recovered to near-normal by 30 min post injury, rCBF in both injured and contralateral (uninjured) forebrain areas remained significantly suppressed up to 1 h post injury. At 2 h post injury, recovery of rCBF to near normal values was observed in all brain regions except the focal area of injury (left parietal cortex) where rCBF remained significantly depressed (p less than 0.01). This prolonged focal oligemia at the injury site was associated with the development of reproducible cystic necrosis in the left parietotemporal cortex at 4 weeks post injury. Our results demonstrate that acute changes in rCBF occur following experimental traumatic brain injury in rats and that rCBF remains significantly depressed up to 2 h post injury in the area circumscribing the trauma site. PMID- 2910894 TI - Fructose-1,6-bisphosphate protects astrocytes from hypoxic damage. AB - To determine the effects of glucose and fructose-1,6-bisphosphate (FDP) on hypoxic cell damage, primary cultures of astrocytes were incubated for 18 h in an air-tight chamber that had been flushed with 95% N2/5% CO2 for 15 min before it was sealed. Cultures containing 7.5 mM glucose without FDP or FDP without glucose showed evidence of significant cell injury after 18 h of hypoxia (increased lactate dehydrogenase content in the culture medium; cell edema and disruption by phase-contrast microscopy). Cultures exposed to glucose + FDP had normal lactate dehydrogenase concentrations and appeared normal microscopically. Maximal protection of hypoxic cells occurred at 6.0 mM FDP. Lactate concentrations of the culture medium of hypoxic cells increased 2.5 times above normoxic control values when glucose was present, but neither FDP alone nor glucose + FDP caused the lactate concentrations to increase further. This implies that anaerobic glycolysis was not increased by adding FDP to the medium. Cell volumes (water space) measured with [14C]-3-0-methyl-D-glucose were normal with glucose + FDP in the culture medium of hypoxic cells but were significantly larger than normal when glucose alone was present. Increases in cell volume paralleled changes in lactate dehydrogenase in the culture medium. Uptake of [14C]FDP occurred rapidly in normoxic cells and was maximal after 5 min of incubation. The data indicate that the presence of glucose + FDP in the culture medium protects primary cultures of hypoxic astrocytes from cell damage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2910895 TI - The deoxyglucose method in the ferret brain. I. Methodological considerations. AB - In the brain of the anesthetized ferret, the 2-deoxyglucose (2-DG) transfer rate constants required to determine cerebral glucose utilization by the deoxyglucose method were calculated from regional gray matter time-radioactivity curves measured for 180 min after tracer injection. Results suggest that loss of metabolized tracer from brain occurs at a rate of about 1%/min for the first 180 min after injection if the rate constant of the rate-limiting step for loss of metabolized tracer (k4*) represents a first-order kinetic process. A simulation experiment shows that, whether k4* is assumed to be 0 or 0.01 min-1, has a negligible influence on glucose utilization rates obtained in conventional 45 min autoradiographic experiments provided that the entire analysis, including lumped constant determination, is carried out in a consistent way. The 2-DG lumped constant for k4* = 0 is 0.54, and 0.68 for k4* = 0.01 min-1. PMID- 2910896 TI - The deoxyglucose method in the ferret brain. II. Glucose utilization images and normal values. AB - To measure cerebral glucose utilization with the autoradiographic deoxyglucose method, the tracer transfer rate constants and lumped constants must be known. 2 Deoxyglucose (2-DG) and fluorodeoxyglucose (FDG) constants were determined in 18 gray and white matter brain structures of the anesthetized ferret. The ferret is a domestic carnivore particularly suitable for deoxyglucose studies because of its small brain size and low body weight. The average gray matter rate constants for tracer transfer across the blood-brain barrier are similar for 2-DG and FDG in the ferret brain (K*1 = 0.21 ml/g/min and k*2 = 0.39 min-1). The rate constant for the rate-limiting step of tracer phosphorylation, k*3, is 1.6 times higher for FDG than for 2-DG (0.21 vs. 0.13 min-1). Loss of metabolized tracer is about 1-1.5%/min throughout the ferret brain for both tracers as estimated for a 180 min experimental period. Taking into account this loss, the lumped constant is 0.92 for FDG and 0.68 for 2-DG. Glucose utilization values in the brain of the anesthesized ferret range from 33 mumol/100 g/min in the corpus callosum to 104 mumol/100 g/min in the caudate nucleus. Representative glucose utilization images of coronal sections of the ferret brain are shown. Brain structures are identified on the same slices counterstained with thionin. PMID- 2910897 TI - Cerebral carbohydrate metabolism during severe ischemia in fetal sheep. AB - The effect of cephalic hypotension on brain metabolism was studied in 10 unanesthetized, normoxic (PaO2 greater than 17 mm Hg), late-gestation fetal lambs. Perfusion pressure (cephalic arterial minus sagittal venous pressure) was 40 +/- 1 mm Hg (SEM) during control and was reduced to 10 +/- 1 by occlusion of the Grachio-cephalic artery. Cerebral blood flow was measured with microspheres, and arterial and sagittal vein blood samples were analyzed for oxygen content, glucose, and lactate. During the occlusion, oxygen consumption decreased from 125 +/- 8 to 95 +/- 4 (p less than 0.05) (all values mumol 100 g-1 min-1), and glucose uptake increased from 20 +/- 3 to 25 +/- 1 (p less than 0.05). During the control period, there was no net lactate flux; during the occlusion, lactate excretion was 5.7 +/- 1.4 (p less than 0.005). The control glucose and oxygen uptakes demonstrated a normal 6:1 molar ratio; however, during the occlusion, 9.4 mumol 100 g-1 glucose min-1 were taken up in excess of expected aerobic glucose metabolism. If all of this glucose were anaerobically metabolized to lactate, three times the measured efflux would be produced. The transport properties of the fetal blood-brain barrier may be important factors in perinatal brain injury. PMID- 2910898 TI - Nimodipine prevents hyperglycemia-induced cerebral acidosis in middle cerebral artery occluded rats. AB - The effects of acute moderate hyperglycemia on local cerebral pH (LCpH) and local cerebral blood flow (LCBF) were studied in rats infused with glucose before middle cerebral artery (MCA) occlusion, and compared with findings in MCA occlusion alone. The effects of nimodipine infusion on LCBF and LCpH in MCA occluded hyperglycemic rats were also studied. LCpH and LCBF were determined simultaneously by a double-label autoradiographic technique. Hyperglycemia was induced by an intraperitoneal injection of 2 g/kg D-glucose before MCA occlusion. Nimodipine-treated rats received the drug as an intravenous infusion of 0.5 micrograms/kg/min starting 15 min after occlusion, and ending at decapitation 4 h postocclusion. Cortical LCpH of five structures in the MCA territory of hyperglycemic rats varied between 6.64 +/- 0.04 and 6.72 +/- 0.02 (mean +/- SEM). These values were significantly lower than LCpH in the same ischemic structures in the control rats, which varied between 6.76 +/- 0.04 and 6.82 +/- 0.03 (p less than 0.05 for four of five structures). Cortical LCpH of hyperglycemic nimodipine treated rats ranged between 6.94 +/- 0.02 and 7.05 +/- 0.02, indicating significant elevations in LCpH (p less than 0.001) compared with the untreated ischemic hyperglycemic animals. LCBF in the ischemic structures was not modified by hyperglycemia or nimodipine treatment. This suggests that nimodipine, by mechanisms other than improvement in blood flow, can prevent the enhanced cerebral tissue acidosis produced by hyperglycemia before incomplete focal ischemia. PMID- 2910899 TI - Transient blood-brain barrier permeability following profound temporary global ischaemia: an experimental study using 14C-AIB. AB - The influence of reperfusion after profound incomplete forebrain ischaemia on blood-brain barrier (BBB) permeability to a small protein tracer was studied in male Sprague-Dawley rats. The mean cortical blood to brain transfer constant (Ki) for 14C-amino isobutyric acid (AIB) was significantly greater at 3 and 6 h of reperfusion, 2.5 times the mean values of controls (p less than 0.05) (2.5 microliter g-1 min-1 and 1.0 microliters g-1 min-1 respectively), but had returned to control values after reperfusion for 24 h. Analysis of distribution of Ki values showed that following 15 min and 30 min of profound ischaemia, there was a significant increase in transfer of AIB across the blood-brain barrier (BBB) after recirculation for up to 6 h, though there was no evidence of protein extravasation as assessed by Evans Blue (EB) dye. After 24 h of reperfusion, the BBB to AIB was restored, and Ki values had returned to control values. It is concluded that following transient global ischaemia, the BBB may recover rapidly. PMID- 2910900 TI - Effect of acute electrode placement on regional CBF in the gerbil: a comparison of blood flow measured by hydrogen clearance, [3H]nicotine, and [14C]iodoantipyrine techniques. AB - Regional cerebral blood flow (rCBF) was compared in the gerbil by means of [3H]nicotine, [14C]-iodoantipyrine, and hydrogen clearance techniques. In agreement with other studies, nicotine and iodoantipyrine methods gave virtually identical results. With these methods, it was observed that a reduction in blood flow occurred shortly after insertion of an electrode into the striatum for hydrogen clearance measurement, affecting rCBF throughout the impaled hemisphere. The reduction was moderate (30%) in the striatum and hippocampus, but much greater (70%) in cortical regions. Identical deficits were observed following brief penetrations involving only cortex. Following chronic electrode placement in the striatum, regional blood flow values obtained with [3H]nicotine returned to the control range within 6 h. Blood flow estimates obtained in the striatum with the implanted electrode increased with a similar time course, so that by 6 24 h, hydrogen clearance gave values indistinguishable from control values obtained with [3H]nicotine. These results clearly demonstrate that reduction of CBF subsequent to electrode placement can account for the low values frequently obtained with the hydrogen clearance method in small animals. The distribution of the deficit and the time course of its recovery are similar to blood flow changes associated with spreading depression. While mechanisms responsible for this effect remain to be fully identified, chronic implantation is a practical solution that allows the continued use of hydrogen clearance as a convenient method for repeated measurement of blood flow in the same animal. PMID- 2910901 TI - Quantitative measurements of regional glucose utilization and rate of valine incorporation into proteins by double-tracer autoradiography in the rat brain tumor model. AB - We examined the rate of glucose utilization and the rate of valine incorporation into proteins using 2-[18F]fluoro-2-deoxyglucose and L-[1-14C]-valine in a rat brain tumor model by quantitative double-tracer autoradiography. We found that in the implanted tumor the rate of valine incorporation into proteins was about 22 times and the rate of glucose utilization was about 1.5 times that in the contralateral cortex. (In the ipsilateral cortex, the tumor had a profound effect on glucose utilization but no effect on the rate of valine incorporation into proteins.) Our findings suggest that it is more useful to measure protein synthesis than glucose utilization to assess the effectiveness of antitumor agents and their toxicity to normal brain tissue. We compared two methods to estimate the rate of valine incorporation: "kinetic" (quantitation done using an operational equation and the average brain rate coefficients) and "washed slices" (unbound labeled valine removed by washing brain slices in 10% trichloroacetic acid). The results were the same using either method. It would seem that the kinetic method can thus be used for quantitative measurement of protein synthesis in brain tumors and normal brain tissue using [11C]-valine with positron emission tomography. PMID- 2910902 TI - Identification of a single nucleotide change in the hypoxanthine-guanine phosphoribosyltransferase gene (HPRTYale) responsible for Lesch-Nyhan syndrome. AB - Complete deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) causes the Lesch-Nyhan syndrome. Previous characterization of a mutant form of HPRT, HPRTYale, from a subject with the Lesch-Nyhan syndrome revealed normal mRNA and protein concentrations, no residual catalytic activity, and cathodal migration upon PAGE. We have cloned and sequenced HPRTYale cDNA. The nucleotide sequence of full-length HPRTYale cDNA revealed a single nucleotide substitution compared with normal HPRT cDNA: G----C at nucleotide position 211. This transversion predicts substitution of arginine for glycine at amino acid position 71, explaining the cathodal migration of HPRTYale. Chou-Fasman secondary structure analysis predicts a change in the probability of beta-turn formation in the region containing the mutation. Inclusion of the bulky arginine side chain in place of glycine probably disrupts protein folding as well. Cloning mutant forms of cDNA allows identification of specific mutations, provides insight into mutational mechanisms, and facilitates structure-function analysis of mutant proteins. PMID- 2910903 TI - Adaptation of the distal convoluted tubule of the rat. Structural and functional effects of dietary salt intake and chronic diuretic infusion. AB - We studied the effects of dietary NaCl intake on the renal distal tubule by feeding rats high or low NaCl chow or by chronically infusing furosemide. Furosemide-treated animals were offered saline as drinking fluid to replace urinary losses. Effects of naCl intake were evaluated using free-flow micropuncture, in vivo microperfusion, and morphometric techniques. Dietary NaCl restriction did not affect NaCl delivery to the early distal tubule but markedly increased the capacity of the distal convoluted tubule to transport Na and Cl. Chronic furosemide infusion increased NaCl delivery to the early distal tubule and also increased the rates of Na and Cl transport above the rates observed in low NaCl diet rats. When compared with high NaCl intake alone, chronic furosemide infusion with saline ingestion increased the fractional volume of distal convoluted tubule cells by nearly 100%, whereas dietary NaCl restriction had no effect. The results are consistent with the hypotheses that (a) chronic NaCl restriction increases the transport ability of the distal convoluted tubule independent of changes in tubule structure, (b) high rates of ion delivery to the distal nephron cause tubule hypertrophy, and (c) tubule hypertrophy is associated with increases in ion transport capacity. They indicate that the distal tubule adapts functionally and structurally to perturbations in dietary Na and Cl intake. PMID- 2910904 TI - Identification of persistent defects in insulin receptor structure and function capillary endothelial cells from diabetic rats. AB - Insulin actions and receptors were studied in capillary endothelial cells cultured from diabetic BB rats and their nondiabetic colony mates. The endothelial cells from diabetic rats of 2 mo duration had persistent biological and biochemical defects in culture. Compared with normal rats, endothelial cells from diabetic rats grew 44% more slowly. Binding studies of insulin and insulin like growth factor I (IGF-I) showed that cells from diabetic rats had 50% decrease of insulin receptor binding (nondiabetic: 4.6 +/- 0.7; diabetic: 2.6 +/- 0.4% per milligram protein, P less than 0.01), which was caused by a 50% decrease in the number of binding sites per milligram protein, whereas IGF-I binding was not changed. Insulin stimulation of 2-deoxy-glucose uptake and alpha aminoisobutyric acid uptake were also severely impaired with a 80-90% decrease in maximal stimulation, in parallel with a 62% decrease in insulin-stimulated autophosphorylation (P less than 0.05). 125I-insulin cross-linking revealed an 140-kD alpha subunit of the insulin receptor similar to that in cells from nondiabetic rats, although bands at greater than 200 kD were also detected. The molecular weight of the insulin receptor beta subunit (by SDS-PAGE) was smaller in cells from diabetic than from normal rats (88-90 vs. 95 kD). Neuraminadase treatment of the partially purified insulin receptors decreased the molecular weight of the insulin receptors from nondiabetic rats to a greater degree than its diabetic counterpart. In contrast, Northern blot analysis of insulin receptor mRNAs using human cDNA probes revealed two species of 9.4 and 7.2 kb with no difference in mRNA abundance between cells from diabetic and nondiabetic rats. We conclude that the exposure of capillary endothelial cells to a diabetic milieu in vivo can cause specific and persistent changes in the insulin receptor and insulin action. PMID- 2910905 TI - Thyroxine transport and distribution in Nagase analbuminemic rats. AB - The postulate that thyroxine (T4) in plasma enters tissues by protein-mediated transport or enhanced dissociation from plasma-binding proteins leads to the conclusion that almost all T4 uptake by tissues in the rat occurs via the pool of albumin-bound T4 (Pardridge, W. M., B. N. Premachandra, and G. Fierer. 1985. Am. J. Physiol. 248:G545-G550). To directly test this postulate, and to test more generally whether albumin might play a special role in T4 transport in the rat, we performed in vivo kinetics studies in six Nagase analbuminemic rats and in six control rats, all of whom had similar serum T4 concentrations and percent free T4 values. Evaluation of the plasma disappearance curves of simultaneously injected 125I-T4 and 131I-albumin indicated that the flux of T4 from the extracellular compartment into the rapidly exchangeable intracellular compartment was similar in the analbuminemic rats (51 +/- 21 ng/min, mean +/- SD) and in the control rats (54 +/- 15 ng/min), as was the size of the rapidly exchangeable intracellular pool of T4 (1.13 +/- 0.53 vs. 1.22 +/- 0.36 micrograms). This latter finding was confirmed by direct analysis of tissue samples (liver, kidney, and brain). We also performed in vitro kinetics studies using the isolated perfused rat liver. The single-pass fractional extraction by normal rat liver of T4 in pooled analbuminemic rat serum was indistinguishable from that of T4 in pooled control rat serum (10.9 +/- 3.3%, n = 3, vs. 11.4 +/- 3.4%). When greater than 98% of the albumin was removed from normal rat serum by chromatography with Affi-Gel blue, the single-pass fractional extraction of T4 (measured by a bolus injection method) did not change (16.3 +/- 2.1%, n = 5, vs. 15.2 +/- 2.5%). These data provide the first valid experimental test of the enhanced dissociation hypothesis and indicate that there is no special, substantive role for albumin in T4 transport in the rat. PMID- 2910906 TI - Unequal decrease in bone density of lumbar spine and ultradistal radius in Colles' and vertebral fracture syndromes. AB - We measured bone mineral density (BMD) at the lumbar spine (LS-BMD) and ultradistal radius (UDR-BMD) in 42 postmenopausal normal women and in 108 postmenopausal osteoporotic women (55 with vertebral fracture, 34 with Colles' fracture, and 19 with both fractures). By receiver operating characteristic analysis, LS-BMD was better than UDR-BMD (P less than 0.01) as an indicator of vertebral fracture; the converse was true for Colles' fracture (P less than 0.01). Although UDR-BMD and LS-BMD were lower in each of the three fracture groups than in controls (P less than 0.01), the pattern of bone loss differed (P less than 0.001, analysis of variance): with vertebral fracture, LS-BMD decreased relatively more than UDR-BMD; with Colles' fracture, UDR-BMD decreased relatively more than LS-BMD; and with both fractures, decreases in LS-BMD and UDR-BMD were similar. We conclude that both types of fracture are caused by excessive bone loss but the difference in bone loss at the two sites is a major factor in determining which will fracture. PMID- 2910907 TI - Muscle cell differentiation is associated with increased insulin receptor biosynthesis and messenger RNA levels. AB - Muscle is a major tissue for insulin action. To study the effect of muscle differentiation on insulin receptors, we employed cultured mouse muscle BC3H-1 and C2 cells. In both cell lines differentiation from myoblasts to myocytes was associated with a 5-10-fold increase in specific 125I-insulin binding to intact cells. When 125I-insulin binding was carried out on solubilized myocytes and myoblasts, 125I-insulin binding to myoblasts was low. After differentiation the number of insulin receptors increased 5-10-fold. In contrast to insulin binding, insulin growth factor I receptor binding was elevated in myoblasts and was decreased by 50% in myocytes. Specific radioimmunoassay of the insulin receptor indicated that the increase in insulin binding to myocytes was due to an increase in insulin receptor content. Studies employing [35S]methionine indicated that this increase in insulin-binding sites reflected an increase in insulin receptor biosynthesis. To study insulin receptor gene expression, myoblast and myocyte mRNA was isolated and analyzed on Northern and slot blots. Differentiation from myoblasts to myocytes was accompanied by a 5-10-fold increase in insulin receptor mRNA. These studies demonstrate, therefore that differentiation in muscle cells is accompanied by increased insulin receptor biosynthesis and gene expression. PMID- 2910908 TI - Regulation of glucose transporter-specific mRNA levels in rat adipose cells with fasting and refeeding. Implications for in vivo control of glucose transporter number. AB - Fasting in the rat is associated with a rapid and progressive decrease in insulin stimulated glucose transport activity in adipose cells, which is not only restored to normal, but increased transiently to supranormal levels by refeeding. The mechanisms for these changes in glucose transport activity appear to involve alterations in both glucose transporter number and intrinsic activity (glucose turnover number). In this study, we use the human hepatoma Hep G2 glucose transporter complementary DNA clone to examine the molecular basis for these alterations. Extractable RNA per adipose cell is decreased 35% with 3 d of fasting and increased to 182% of control with 6 d of refeeding after 2 d of fasting. This parallels changes in adipose cell intracellular water, so that total RNA/water space remains relatively constant. When the changes in total RNA/cell are taken into account, Northern and slot blot analyses with quantitative densitometry reveal a 36% decrease in specific glucose transporter mRNA level in cells from the fasted rats. The mRNA level in cells from the fasted/refed rats is restored to normal. These observations correlate closely with previous measurements of glucose transporter number in adipose cell membrane fractions using cytochalasin B binding and Western blotting. The levels of specific mRNAs for tubulin and actin on a per cell basis show similar but more dramatic changes and mRNAs encoding several differentiation-dependent adipose cell proteins are also significantly affected. Thus, the levels of mRNA for multiple adipose cell genes are affected by fasting and refeeding. In particular, this demonstrates that in vivo metabolic alterations can influence the level of a glucose transporter mRNA in adipose cells. This may have implications for the regulation of glucose transporter number and glucose transport activity. PMID- 2910909 TI - Inhibition of activated protein C by platelets. AB - Activated protein C (APC), an anticoagulant that acts by inactivating Factors Va and VIIIa, is dependent on a suitable surface for its action. In this study we examined the ability of human platelets to provide this surface and support APC mediated anticoagulant effects. The activity of APC was examined in three systems: the Factor Xa recalcification time of Al(OH)3 adsorbed plasma, studies of thrombin generation in recalcified plasma, and assessment of the rate of inactivation of purified Factor Va. In comparison with phospholipid, intact platelets required significantly greater concentrations of APC to achieve a similar degree of anticoagulation. When washed platelet membranes were substituted for intact platelets, adequate support of APC was observed and the anticoagulant effect was similar to that obtained with phospholipid. Platelet releasate obtained by stimulation of platelets with thrombin and epinephrine contained an inhibitor that interfered with the ability of phospholipid and washed platelet membranes to catalyze the anticoagulant effects of APC. A noncompetitive inhibition was suggested by Dixon plot analysis of the interaction between platelet releasate and APC. The activity of the platelet APC inhibitor was immediate and was not enhanced by heparin, distinguishing it from the circulating protein C inhibitor. The presence of this inhibitor in the platelet and its release with platelet stimulation emphasizes the procoagulant role of this cell. PMID- 2910910 TI - Cytoplasmic pH regulation and chloride/bicarbonate exchange in avian osteoclasts. AB - Osteoclasts resorb bone by first attaching to the bone surface and then secreting protons into an isolated extracellular compartment formed at the cell-bone attachment site. This secretion of protons (local acidification) is required to solubilize bone hydroxyapatite crystals and for activity of bone collagen degrading acid proteases. However, the large quantity of protons required, 2 mol/mol of calcium, would result in an equal accumulation of cytosolic base equivalents. This alkaline load must be corrected to maintain cytosolic pH within physiologic limits. In this study, we have measured cytoplasmic pH with pH sensitive fluorescent compounds, while varying the extracellular ionic composition of the medium, to determine the nature of the compensatory mechanism used by osteoclasts during bone resorption. Our data show that osteoclasts possess a chloride/bicarbonate exchanger that enables them to maintain normal intracellular pH in the face of a significant proton efflux. This conclusion follows from the demonstration of a dramatic cytoplasmic acidification when osteoclasts that have been incubated in bicarbonate-containing medium are transferred into bicarbonate-free medium. This acidification is absolutely dependent on and proportional to medium [Cl-]. Furthermore, acidification is inhibited by the classic inhibitor of red cell anion exchange, 4,4' diisothiocyanatostilbene-2,2'-disulfonate, and by diphenylamine-2-carboxylate, an inhibitor of chloride specific channels. However, the acidification process is neither energy nor sodium dependent. The physiologic importance of chloride/bicarbonate exchange is demonstrated by the chloride dependence of recovery from an endogenous or exogenous alkaline load in osteoclasts. We conclude that chloride/bicarbonate exchange is in large part responsible for cytoplasmic pH homeostasis of active osteoclasts, showing that these cells are similar to renal tubular epithelial cells in their regulation of intracellular pH. PMID- 2910911 TI - Duodenal iron proteins in idiopathic hemochromatosis. AB - This study was undertaken to assess the relationship between iron absorption and the concentration of duodenal iron proteins in normal subjects and patients with idiopathic hemochromatosis (IH). Biopsies were obtained endoscopically from the duodenum in 17 normal subjects, 3 of whom were mildly iron deficient, and 7 patients with untreated IH. The absorption of both heme and nonheme iron was increased in IH despite a 20-fold elevation in serum ferritin. Immunoassays using MAb were used to measure transferrin, H-rich ferritin, and L-rich ferritin in mucosal samples. Mucosal transferrin concentrations in normal subjects did not correlate with either iron status or iron absorption, indicating that mucosal transferrin plays no physiological role in iron absorption. Mucosal transferrin was significantly lower in IH, presumably because of a decrease in mucosal transferrin receptors. Mucosal H and L ferritin concentrations were directly related to body iron stores and inversely related to iron absorption in normal subjects. In IH, mucosal H and L ferritin failed to increase in parallel with the serum ferritin, but were appropriate for the level of iron absorption. The relationship of mucosal H/L ferritin in IH did not differ from that observed in normal subjects. Our findings indicate that the major abnormality in duodenal iron proteins in IH is a parallel decrease in the concentration of H- and L-rich ferritin. It is not evident whether this is the result or the cause of the absorptive abnormality. PMID- 2910912 TI - Fibrinogen-independent platelet adhesion and thrombus formation on subendothelium mediated by glycoprotein IIb-IIIa complex at high shear rate. AB - Platelet adhesion and thrombus formation on subendothelium, studied at a shear rate of 2,600 s-1, were inhibited by two synthetic peptides known to interact with GPIIb-IIIa. One peptide (HHLGGAKQAGDV) corresponds to the carboxyl terminal segment of the fibrinogen gamma-chain (gamma 400-411) and the other (RGDS) contains the amino acid sequence Arg-Gly-Asp (RGD) common to fibronectin, von Willebrand factor, vitronectin and the alpha-chain of fibrinogen. Neither platelet adhesion nor thrombus formation were decreased in a patient with severe congenital fibrinogen deficiency and this was equally true when his blood was further depleted of the small amounts of fibrinogen present utilizing an anti fibrinogen antibody. In normal subjects, adhesion and thrombus formation were inhibited by the Fab' fragments of a monoclonal anti-GPIIb-IIIa antibody (LJ CP8), which interferes with the interaction of platelets with all four adhesive proteins in both the fluid and solid phase. However, another anti-GPIIb-IIIa antibody (LJ-P5) that had minimal effects on the interaction of platelets with fibrinogen, but inhibited to varying degrees platelet interaction with other adhesive proteins, was equally effective. The findings demonstrate that, at a shear rate of 2,600 s-1, adhesive proteins other than fibrinogen are involved in GPIIb-IIIa-mediated platelet adhesion and thrombus formation on subendothelium. In addition, since LJ-P5 inhibited the binding of soluble von Willebrand factor and vitronectin, these adhesive proteins may be involved in platelet thrombus formation. In contrast to the results obtained at a shear rate of 2,600 s-1, fibrinogen could play a role in mediating platelet-platelet interactions with weak agonists or lower shear rates. PMID- 2910913 TI - Biliary copper excretion by hepatocyte lysosomes in the rat. Major excretory pathway in experimental copper overload. AB - We investigated the hypothesis that lysosomes are the main source of biliary copper in conditions of hepatic copper overload. We used a rat model of oral copper loading and studied the relationship between the biliary output of copper and lysosomal hydrolases. Male Sprague-Dawley rats were given tap water with or without 0.125% copper acetate for up to 36 wk. Copper loading produced a 23-fold increase in the hepatic copper concentration and a 30-65% increase in hepatic lysosomal enzyme activity. Acid phosphatase histochemistry showed that copper loaded livers contained an increased number of hepatocyte lysosomes; increased copper concentration of these organelles was confirmed directly by both x ray microanalysis and tissue fractionation. The copper-loaded rats showed a 16-fold increase in biliary copper output and a 50-300% increase in biliary lysosomal enzyme output. In the basal state, excretory profiles over time were similar for biliary outputs of lysosomal enzymes and copper in the copper-loaded animals but not in controls. After pharmacologic stimulation of lysosomal exocytosis, biliary outputs of copper and lysosomal hydrolases in the copper-loaded animals remained coupled: injection of colchicine or vinblastine produced an acute rise in the biliary output of both lysosomal enzymes and copper to 150-250% of baseline rates. After these same drugs, control animals showed only the expected increase in lysosomal enzyme output without a corresponding increase in copper output. We conclude that the hepatocyte responds to an increased copper load by sequestering excess copper in an increased number of lysosomes that then empty their contents directly into bile. The results provide direct evidence that exocytosis of lysosomal contents into biliary canaliculi is the major mechanism for biliary copper excretion in hepatic copper overload. PMID- 2910914 TI - Antagonism of thyroid hormone action by amiodarone in rat pituitary tumor cells. AB - A thyroid hormone antagonist has not been previously described. A number of thyroid hormone analogues have been shown to compete with [125I]triiodothyronine ([125I]T3) for binding to the intranuclear thyroid hormone receptor and to have agonist activity proportional to their affinities for the receptors. We report that the benzofuran amiodarone acts as a competitive antagonist to thyroid hormone action as defined by its dose-dependent ability to (a) bind to the thyroid hormone receptor and (b) inhibit T3-induced increases in growth hormone mRNA levels in a cultured rat pituitary cell line, GC cells. Like T3 itself, amiodarone also decreases transport of [125I]T3 across GC cell membranes. An analysis of the amiodarone structure suggests that this compound has certain similarities to T3. These findings hold promise for the development of other thyroid hormone antagonists for clinical use and for understanding thyroid hormone action. PMID- 2910915 TI - Novel tool for the study of cholecystokinin-stimulated pancreatic enzyme secretion. AB - The molecular events that mediate cholecystokinin (CCK)-stimulated pancreatic secretion are not well defined because of the complex receptor-binding and concentration-response characteristics of this hormone. Functional models of receptor occupancy initiating the cascade leading to secretion have been complicated by the inhibition of secretion effected by supramaximal concentrations of CCK. Recent report of a CCK analogue that does not exhibit supramaximal inhibition led us to synthesize a similar analogue that could also be radiolabeled for studies of receptor binding and affinity labeling, and for studies of second messenger activity. This probe, D-Tyr-Gly-[(Nle28,31)CCK-26-32] phenethyl ester, was a fully efficacious secretagogue with no supramaximal inhibition, and, unlike native hormone, bound to a single class of sites present on both acini and membranes. Occupation of this site correlated well with stimulation of secretion. Evidence that this was indeed a CCK-binding site were the abilities of CCK and the antagonist L-364, 718 to inhibit binding of this analogue. Affinity labeling confirmed the identity of the site mediating secretory stimulation as a Mr = 85,000-95,000 protein. Whereas the nonhydrolyzable guanosine triphosphate analogue, 5'-guanylyl-imidodiphosphate, was a potent inhibitor of CCK binding, it had no effect on binding of this secretagogue, suggesting that a novel cascade not involving a guanine nucleotide binding protein mediates CCK stimulation of pancreatic secretion. PMID- 2910916 TI - Evidence that insulin-like growth factor I increases renal plasma flow and glomerular filtration rate in fasted rats. AB - The mechanisms whereby growth hormone may increase renal plasma flow (RPF) and GFR are not known, but circumstantial evidence has implicated insulin-like growth factor I (IGF-I) as a mediator of this effect. This study examined whether an infusion of IGF-I will increase RPF and GFR, whether this effect occurs quickly, and if this effect is dependent on eicosanoids or peptide hormones known to affect renal function. Rats fasted for 3 d to reduce IGF-I and IGF-I plasma binding proteins were anesthetized; then the rats received an intravenous injection of 25 micrograms/kg IGF-I, and an infusion of 25 micrograms/kg IGF-I within 20 min. Controls received infusion of the vehicle. RPF (para aminohippurate clearances), GFR (inulin clearances), renal vascular resistance (RVR), mean arterial blood pressure (MABP), plasma IGF-I, and glucose concentrations were measured repeatedly. At the end of the 20-min infusion, plasma IGF-I tended to be increased in the animals that received IGF-I (P = 0.069), but did not increase in the control rats. IGF-I induced a significant and sustained fall in RVR and rise in RPF and GFR without any change in MABP. A small, transient, but significant decrease in plasma glucose concentrations was observed during IGF-I but not during vehicle infusion. Indomethacin, but not somatostatin, blocked the renal response to IGF-I infusion. Thus, IGF-I infusion increases RPF and GFR and reduces RVR in fasted rats. This effect requires the presence of eicosanoids but does not seem to require other peptide hormones suppressed by somatostatin. PMID- 2910917 TI - Alternative splicing of human glucose-6-phosphate dehydrogenase messenger RNA in different tissues. AB - Different forms of glucose-6-phosphate dehydrogenase (G-6-PD) have been described in different tissues. Moreover, the directly determined amino acid sequence amino end of the red cell enzyme does not exactly match the sequence deduced from cDNA isolated from HeLa cells or lymphoblasts. We have therefore investigated the sequence of cDNA from sperm, granulocytes, reticulocytes, brain, placenta, liver, lymphoblastoid cells, and cultured fibroblasts. A novel human cDNA, which has extra 138 bases coding 46 amino acids, was isolated from a lymphoblastoid cell library. Sequencing of genomic DNA amplified by the polymerase chain reaction (PCR) revealed that the extra sequence was derived from the 3'-end of intron 7 by alternative splicing. This longer form of mRNA was also detected in sperm and granulocytes. Sequence analysis using PCR-amplified cDNA revealed that the 5'-end of the coding sequence of G6PD mRNA in reticulocytes is identical to those in other tissues. PMID- 2910918 TI - Effects of combined estrogen and progestin administration on plasma lipoprotein metabolism in postmenopausal women. AB - Treatment of postmenopausal women with low doses of estradiol-17 beta (1 mg/d) and dl-norgestrel (0.075 [corrected] mg/d) significantly reduced fasting serum levels of low density lipoprotein (LDL) cholesterol and lowered very low density lipoprotein (VLDL) triglycerides in four of five subjects. To explain these results, the kinetics of VLDL and LDL apolipoprotein (apo) B turnover were studied by injecting autologous 125I-labeled VLDL and 131I-labeled LDL into subjects before discontinuing long-term (4-yr) treatment with the estradiol-17 beta and dl-norgestrel and again 7 wk after stopping treatment. The 24% mean decrease in VLDL apo B pool size during treatment was associated with a significant increase in VLDL apo B fractional catabolic rate (15 +/- 1 vs. 11 +/- 1 pools/d), whereas production rate was similar to control (24 +/- 3 vs. 21 +/- 2 mg/kg per d). There was a significant 25% mean decrease in LDL apo B pool size (27 +/- 2 vs. 36 +/- 3 mg/kg) due to a significant decrease in total (8.3 +/- 0.3 vs. 11 +/- 1 mg/kg per d) and independent (3.3 +/- 0.5 vs. 6.6 +/- 0.8 mg/kg per d, P less than 0.05) LDL apo B production. Estradiol-17 beta together with dl norgestrel lowered plasma VLDL by enhancing their clearance and LDL by reducing their production. PMID- 2910919 TI - Splanchnic and renal exchange of infused fructose in insulin-deficient type 1 diabetic patients and healthy controls. AB - Fructose raises blood glucose and lactate levels in normal as well as diabetic man, but the tissue origin (liver and/or kidney) of these responses and the role of insulin in determining the end products of fructose metabolism have not been fully established. Splanchnic and renal substrate exchange was therefore examined during intravenous infusion of fructose or saline in six insulin-deficient type I diabetics who fasted overnight and in five healthy controls. Fructose infusion resulted in similar arterial concentrations and regional uptake of fructose in the two groups. Splanchnic glucose output increased threefold in the diabetics but remained unchanged in controls in response to fructose infusion, and the arterial glucose concentration rose more in diabetics (+5.5 mmol/liter) than in controls (+0.5 mmol/liter). Splanchnic uptake of both lactate and pyruvate increased twofold in response to fructose infusion in the diabetics. In contrast, a consistent splanchnic release of both lactate and pyruvate was seen during fructose infusion in controls. In diabetics fructose-induced hyperglycemia was associated with no net renal glucose exchange, while there was a significant renal glucose production during fructose infusion in the controls. In both groups fructose infusion resulted in renal output of lactate and pyruvate. In the diabetics this release corresponded to the augmented uptake by splanchnic tissues. In two diabetic patients given insulin infusion, all responses to fructose infusion were normalized. Fructose infusion in diabetics did not influence either splanchnic ketone body production or its relationship to splanchnic FFA inflow. We conclude that in insulin-deficient, mildly ketotic type I diabetes, (a) both the liver, by virtue of lactate, pyruvate, and fructose derived gluconeogenesis, and the kidneys , by virtue of fructose-derived lactate and pyruvate production, contribute to fructose-induced hyperglycemia; (b) outcome of hepatic fructose metabolism; and (c) fructose does not exert an antiketogenic effect. These data suggest that while total fructose metabolism is not altered in diabetics, intermediary hepatic fructose metabolism is dependent on the presence of insulin. PMID- 2910920 TI - Insulin-like growth factor I mediates selective anabolic effects of parathyroid hormone in bone cultures. AB - PTH was studied for its effects on bone formation in cultured rat calvariae. 0.01 10 nM PTH stimulated [3H]thymidine incorporation into DNA by up to 4.8-fold. Although continuous treatment with PTH for 24-72 h inhibited [3H]proline incorporation into collagen, transient (24 h) treatment enhanced [3H]proline incorporation into collagen 24-48 h after the hormone was removed. The collagen stimulated by PTH was type I and the effect was observed in the periosteum-free bone and was not blocked by hydroxyurea. Furthermore, treatment with 1-100 nM PTH for 24 h increased insulin-like growth factor (IGF) I concentrations by two to fourfold, and an IGF I antibody prevented the PTH stimulation of collagen synthesis, but not its mitogenic effect. In conclusion, continuous treatment with PTH inhibits calvarial collagen, whereas transient treatment stimulates collagen synthesis, and the stimulatory effect is mediated by local production of IGF I. PMID- 2910921 TI - Reduction of dietary phosphorus absorption by phosphorus binders. A theoretical, in vitro, and in vivo study. AB - Antacids used to decrease phosphorus absorption in patients with renal failure may be toxic. To find more efficient or less toxic binders, a three-part study was conducted. First, theoretical calculations showed that phosphorus binding occurs in the following order of avidity: Al3+ greater than H+ greater than Ca2+ greater than Mg2+. In the presence of acid (as in the stomach), aluminum can therefore bind phosphorus better than calcium or magnesium. Second, in vitro studies showed that the time required to reach equilibrium varied from 10 min to 3 wk among different compounds, depending upon solubility in acid and neutral solutions. Third, the relative order of effectiveness of binders in vivo was accurately predicted from theoretical and in vitro results; specifically, calcium acetate and aluminum carbonate gel were superior to calcium carbonate or calcium citrate in inhibiting dietary phosphorus absorption in normal subjects. We concluded that: (a) inhibition of phosphorus absorption by binders involves a complex interplay between chemical reactions and ion transport processes in the stomach and small intestine; (b) theoretical and in vitro studies can identify potentially better in vivo phosphorus binders; and (c) calcium acetate, not previously used for medical purposes, is approximately as efficient as aluminum carbonate gel and more efficient as a phosphorus binder than other currently used calcium salts. PMID- 2910922 TI - Subcortical cerebral hemorrhages associated with cocaine abuse: CT and MR findings. AB - Four young individuals with histories of heavy cocaine abuse occurring several hours to days before the development of acute symptoms of severe headaches, disorientation, and subsequent stupor were shown to harbor subcortical cerebral hemorrhages. Thorough workup of these patients revealed no underlying pathology (i.e., arteriovenous malformations) or other possible causes such as hemorrhage into a tumor. It is well known that heroin, ephedrine, and methamphetamine use may result in cerebral vasculitis, but only one case study in the literature has reported on cerebral vasculitis with ischemic stroke secondary to cocaine abuse. The possibility of heavy cocaine use should be considered, along with the previously mentioned drugs, when a young, previously healthy person presents with a deep cerebral hemorrhage. PMID- 2910923 TI - CT appearance of mycotic abdominal aortic aneurysms. AB - The CT appearance of three cases of infected aortic aneurysms is reported with clinical and pathological correlation. Two of our cases had unique features: the disappearance of aortic calcifications, and an irregular, thickened aortic wall with peripheral enhancement. The nonspecific clinical presentation and high mortality make mycotic aneurysm an important consideration in the differential diagnosis of abnormal soft tissue contiguous with the aorta. PMID- 2910924 TI - MR imaging of anterior cruciate ligament repair. AB - Magnetic resonance (MR) imaging is an accurate means of analyzing disruptions of the native anterior cruciate ligament (ACL). Various techniques may be used to repair a disrupted ACL. A common repair is the MacIntosh lateral-substitution over-the-top repair in which a strip of fascia lata from the iliotibial band is used as a "neoligament." The results of 27 MR examinations of 17 athletes with this repair were analyzed to determine the appearance of the neoligament on MR. Thirteen of the 17 patients had returned to full athletic activity and four were capable of strenuous activity. Examinations were made at both 0.5 and 1.5 T in varied extents of external rotation from 0 to 20 degrees, and at variable time intervals after surgery from 1 to nearly 40 months. Only two patients clinically required postrepair arthroscopy, but both had normal repairs. Neoligaments were classified as well-defined (n = 6 studies), ill-defined (n = 10), and not discernible (n = 11), based on clarity of appearance. Reasons for this variable appearance include the variable presence of fibrous and fatty tissue investing the neoligament. We conclude that the normal neoligament, unlike the normal active ACL, has a variable appearance, including nonvisualization on MR and that criteria used in evaluating the native ligament will be inadequate to assess the repair. PMID- 2910926 TI - Serial MR studies in Menkes disease. AB - We describe a characteristic combination of findings in a patient with Menkes disease who was serially imaged with magnetic resonance over 2 months. Abnormal intracranial vessels were demonstrated as was the progression of white matter disease. PMID- 2910925 TI - Sarcoidosis of the pineal region: CT and MR studies. AB - An isolated sarcoid involvement of the pineal region is reported. This case is of interest because of an unusual clinical onset, an exceptional location, and a positive response to radiotherapy after unsuccessful steroid therapy. The evolution of this case as shown by CT and magnetic resonance studies is discussed. PMID- 2910927 TI - MR findings in Meige syndrome. AB - A 65-year-old woman was diagnosed clinically to have Meige syndrome in the oromandibular dystonic clinical variant of Marsden. On magnetic resonance imaging a reduced signal intensity in the head of the caudate nuclei, more prominent on the right, and in both putamina was shown. PMID- 2910928 TI - Sneddon syndrome: CT, arteriography, and MR imaging. AB - We report a rare case of Sneddon syndrome, which consists of livedo reticularis and cerebrovascular lesions. The syndrome is characterized by occlusions of medium-sized arteries manifest particularly in the extremities and in the cerebrum. The spectrum of neuroradiological findings in this clinical entity are illustrated and discussed. PMID- 2910929 TI - Myxoma of the heart presenting with recurrent episodes of hemorrhagic cerebral infarction: MR findings. AB - A case of surgically proven left atrial myxoma presented with multiple episodes of cerebral infarctions, both ischemic and hemorrhagic, documented on serial CT and magnetic resonance (MR). Magnetic resonance studies showed, as well, dilated blood vessels in the hemorrhagic areas, proven by angiography to represent mycotic aneurysms. One of these lesions was surgically removed and confirmed to represent a combination of hematoma, infarction, myxomatous nodules, and underlying mycotic aneurysms, as shown on MR scans. This case demonstrates a known delayed neurologic complication of cardiac myxoma that can occur long after resection of the tumor. PMID- 2910930 TI - Computed tomography of mediastinal hematoma secondary to unusual esophageal laceration: a Boerhaave variant. AB - The Boerhaave syndrome is classically considered a panmural perforation of the distal esophagus secondary to forced vomiting or retching. A variant of the syndrome is described in which only the outer longitudinal muscle layer of the esophagus was torn, and in this case most of the usual radiological findings were absent. The clinical, radiological, and surgical findings are discussed. PMID- 2910931 TI - Benign mediastinal cysts: pointed appearance on CT. AB - A case of bronchogenic cyst and two cases of pericardial cysts are presented. Our report illustrates the diagnostic utility of a pointed contour and the dependence of contour on position on CT in establishing the cystic nature of mediastinal mass. PMID- 2910932 TI - Osler-Weber-Rendu disease: MR findings in the liver. AB - We report the magnetic resonance (MR) findings in the liver of a patient with known Osler-Weber-Rendu disease, a rare disorder characterized by arteriovenous malformations involving multiple organ systems. To the best of our knowledge, the MR findings in liver involvement have not been previously reported. PMID- 2910933 TI - Uncomplicated portal venous gas associated with duodenal perforation following ERCP: CT features. AB - Visualization of portal venous air in adults is usually an ominous sign of impending death. The case reported below demonstrates portal vein gas with a benign course in a patient with a duodenal perforation following endoscopic retrograde cholangiopancreatography. PMID- 2910934 TI - Pancreatic pseudotumor in pancreas divisum: CT characteristics. AB - We report a case in which a focally spared area of pancreatic tissue in a gland otherwise replaced by fat created a "pseudomass" mimicking neoplasm on sonography and CT. The "pseudomass" appearance was related to the anomalous ductal anatomy in pancreas divisum. The spared area of pancreas creating a "pseudomass" was drained by the dorsal duct and the remainder of the pancreas that had undergone relative fatty replacement was drained by the ventral duct. PMID- 2910935 TI - CT diagnosis of bowel herniation at pelvic fracture site. AB - We report the rare, but potentially fatal, complication of bowel herniation through a pelvic fracture. Findings on CT led to detection of this abnormality. PMID- 2910936 TI - Contrast material in posterior vaginal fornix mimicking bladder rupture: CT features. AB - Abdominopelvic CT of a 22-year-old woman who sustained blunt abdominal trauma revealed a collection of contrast material posterior to the bladder. This CT appearance was interpreted as evidence of bladder rupture, despite previously performed normal retrograde cystography. Subsequent urologic studies confirmed the absence of bladder injury. Retrospective review of CT revealed that collection was within the vagina. This case demonstrates an important false positive CT diagnosis of bladder rupture and confirms the importance of retrograde cystography for the diagnosis of bladder rupture. PMID- 2910937 TI - Computed tomography of elephantiasis neuromatosa. AB - A case of an unusually symmetric and grotesque elephantiasis neuromatosa of the trunk is presented. Computed tomography demonstrated the extent of the disease, which is essential if surgery is planned. PMID- 2910938 TI - MR image of localized giant cell tumor of the tendon sheath involving the knee. AB - A case of giant cell tumor of the tendon sheath is presented. The CT and magnetic resonance appearances are described, correlated with pathologic findings, and compared with those of villonodular synovitis. PMID- 2910939 TI - Sternocleidomastoid fibrosis in congenital muscular torticollis: MR appearance. PMID- 2910940 TI - Computed tomography of cervical epidermoid cysts. PMID- 2910941 TI - Stereoscopic MR imaging. AB - The visual fusion of two projection or slice-selective magnetic resonance (MR) images taken at two oblique angles imparts three-dimensional (3D) information within the projection or slice. This approach to 3D MR is rapid and straightforward, requiring only two oblique images and, at most, only a simple optical stereoscope for viewing. Stereoscopic images of the vascular system of a rat were obtained using the intravascular contrast agent albumin-(Gd diethylenetriaminepentaacetic acid). Stereoscopic images of the human head showing CSF distribution were acquired using a long echo time sequence. These images illustrate the potential clinical applications of this technique. PMID- 2910942 TI - High quality zoomed MR images. AB - A zooming technique based on zero filling of the Fourier space is presented for high quality magnification of magnetic resonance magnitude images. Comparison with conventional linear interpolation methods on two clinical examples indicates that Fourier magnification is preferable because it avoids image artifacts and provides superior image quality. It is recommended that this technique become the standard method of magnification on all imagers. PMID- 2910943 TI - Gantry tilt technique for CT-guided biopsy and drainage. AB - An angled approach to percutaneous biopsy or drainage using CT guidance is often required to avoid transgressing vital intervening structures. We describe a simple technique for CT-guided angled biopsy. By tilting the CT gantry off the axial plane, CT scans can be obtained that directly demonstrate the appropriate angle of approach while avoiding intervening structures. The gantry tilt technique provides direct visualization of the pathway of the needle tract; direct visualization is not possible with previously described techniques such as stereotactic biopsy or the triangulation technique. The gantry tilt technique is a practical, simple means for performing angled CT biopsy or aspiration in many cases. PMID- 2910944 TI - MR imaging of lytic changes in Paget disease of the calvarium. AB - The authors present two patients with Paget disease, both showing lytic changes in the calvarium. On T1 contrast sequences, the first patient demonstrated an extraaxial soft tissue mass in the temporooccipital region. This abnormality was hypointense to the adjacent normal diploic tissue. The second patient demonstrated a hypointense frontal abnormality on the T1-weighted sequence. Intracranial extension of this lesion was associated with lysis in otherwise mixed signal pagetoid bone. The first patient had osteoclastic Paget disease or osteoporosis circumscripta. The second patient had sarcomatous degeneration. PMID- 2910945 TI - Gadolinium-DTPA enhanced MR imaging of spinal dural arteriovenous fistulas. AB - To evaluate the role of magnetic resonance (MR) in the diagnosis of dural arteriovenous (AV) fistulas and the resulting myelopathy, the MR examinations of 11 patients with symptoms and signs of slowly progressive myelopathy of the lower spinal cord have been reviewed. Patients with intradural or extradural AV malformations were excluded. Six patients have been examined without the use of a contrast agent. The other five patients were studied prior and after intravenous administration of gadolinium-diethylenetriamine pentaacetic acid (DTPA). Serpentine linear areas of low signal due to flow void effects within the subdural space have been detected in seven patients. The T1-weighted sagittal images and T2-weighted sagittal and axial images demonstrated signal intensity changes within the center of the cord due to prolongation of T1 and T2 relaxation times. In addition, a relatively abrupt increase of the sagittal and transverse diameters of the lower thoracic cord was found in all cases. In nine patients T1 weighted, proton-density and T2-weighted sagittal images presented "blurred" margins of the lower thoracic cord. After intravenous administration of Gd-DTPA (0.1 mmol/kg), contrast enhancement was present not only within these vessels but also within the lower spinal cord. There was only slight enhancement of the cord immediately after injection of the contrast agent, but significant enhancement was observed 40-45 min later. PMID- 2910946 TI - CT demonstration of spinal epidural emphysema complicating bronchial asthma and violent coughing. PMID- 2910947 TI - CT characteristics of orbital pseudotumors and other orbital inflammatory processes. AB - Orbital pseudotumor is a nonspecific inflammatory process of unknown etiology that may mimic a true orbital neoplasm, specifically lymphoma. It exhibits a highly variable clinical and radiographic presentation. Thirty-nine patients with a presumptive diagnosis of orbital inflammatory disease were examined with CT and evaluated with respect to 13 findings associated with inflammatory disease of the orbit. Pseudotumor was included as part of the differential diagnosis in 25 patients. Twenty-one cases received a final (clinical) diagnosis of pseudotumor. The remainder were comprised of a broad range of orbital inflammatory conditions. Key radiographic features required to entertain or exclude the diagnosis of pseudotumor included establishing the presence of an orbital mass, extraocular muscle enlargement, bony erosion, enhancement, and associated paranasal sinus disease. PMID- 2910948 TI - Pulmonary lymphangioleiomyomatosis: CT and pathologic findings. AB - We present two cases that illustrate the appearance of pulmonary lymphangioleiomyomatosis on high resolution CT. Both patients had numerous thin walled cystic airspaces of varying sizes distributed diffusely throughout the lungs. Most of the lung parenchyma surrounding the cystic spaces was normal. This pattern correlated closely with the surgical and pathologic findings and is distinct from other diffuse lung diseases. PMID- 2910949 TI - Recurrent esophageal carcinoma at thoracotomy incisions: diagnostic contributions of CT. AB - Three cases of surgical implantation of esophageal carcinoma during esophagogastrectomy are presented. The CT and radiographic appearance is demonstrated. A possible etiology and method for decreasing the risk of surgical spread of tumor are discussed. PMID- 2910950 TI - Gadolinium-phthalein complexone as a contrast agent for hepatobiliary MR imaging. AB - Gadolinium-phthalein complexone (Gd-PC) was developed as a hepatobiliary magnetic resonance (MR) contrast agent. Phthalein complexone is one of the iminodiacetic acid derivatives and a structural analogue of bromosulfophthalein. Gadolinium-PC substantially enhanced signal intensity of normal functioning livers on T1 weighted MR images. Contrast enhancement of rabbit liver and gradual accumulation of high intensity bile in the gallbladder were observed after intravenous injection of 0.05 and 0.1 mmol/kg Gd-PC. However, 0.1 mmol/kg of Gd-DTPA caused little effect on liver MR. PMID- 2910951 TI - Computed tomography of unusual calcified pancreatic tumors. AB - Two unusual pancreatic tumors, a pancreatic fibroma and a solid and papillary neoplasm of the pancreas, are described. Both appeared to be heavily calcified on CT examination, a feature that has not been reported. PMID- 2910952 TI - Effects of lithotripsy on rat kidney: evaluation with MR imaging, histology, and electron microscopy. AB - Magnetic resonance (MR) imaging at 1.5 T was used to evaluate the effects of extracorporeal shock wave lithotripsy (ESWL) in 30 rats and the findings on T1- and T2-weighted (spin echo 600/22, 1,600-2,000/90) images were compared with histology and scanning microscopy. The observed pathologic changes increased in severity with the number of shock waves given (500-5,000 15 kV). Post-ESWL MR findings in 54 kidneys included perirenal and subcapsular fluid (n = 30), diffuse loss of corticomedullary junction definition (n = 28), intrarenal foci of increased (n = 7) or decreased (n = 6) signal intensity, focal indentation of the renal contour (n = 5), and loss of distinction between the renal, splenic, or hepatic contour (n = 7). The subcapsular and intrarenal findings corresponded pathologically to areas of hemorrhage and hematoma formation--the contour changes to foci of renal scarring or perirenal adhesions. Electron microscopy demonstrated marked alterations of the renal tubules and vasculature. The study shows the feasibility of assessing the nature and chronology of renal damage post ESWL in a rat model by MR. PMID- 2910953 TI - Bladder involvement in Crohn disease: role of CT in detection and evaluation. AB - A retrospective review of 275 consecutive patients with symptomatic Crohn disease to determine the frequency and type of bladder involvement yielded 14 cases. All 14 patients had a long standing history of Crohn disease with other positive radiologic features at the time of detection of bladder involvement. Patients were categorized into two groups based on the CT findings: Group I (n = 4) had focal bladder wall thickening adjacent to an extravesical soft tissue mass and/or focal bowel wall thickening; Group II (n = 10) had fistula formation with intravesical air with associated focal bowel wall thickening and/or extravesical soft tissue mass. Bladder involvement in Crohn disease is a progressive pathological process that can result in formation of an enterovesical fistula. The patient may come to radiologic attention at any stage in the course of the disease. Computed tomography is a sensitive and noninvasive method of evaluating the bladder and can be used to identify patients in the prodromal stage who are at risk of developing enterovesical fistulae. Timely intervention may prevent frank perforation into the lumen of the bladder by an inflammatory mass. PMID- 2910954 TI - Difference in amounts between titratable acid and total carboxylic acids produced by oral streptococci during sugar metabolism. AB - The acid produced by the resting cells of Streptococcus mutants NCTC 10449 and HS 6 and S. sanguis ATCC 10556 during sugar metabolism was estimated with a pH-stat and a carboxylic acid analyzer. Lactic, formic, acetic, pyruvic, and carbonic acids were detected in the reaction mixtures, but propionic, citric, succinic, iso-butyric, butyric, iso-valeric, and valeric acids were not detected. The amount of titratable acid estimated by alkaline titration with the pH-stat was larger than the amount of total carboxylic acids estimated with the carboxylic acid analyzer. The difference in quantity between the titratable and the total carboxylic acids increased significantly with an increase in the period of incubation with sugar. Moreover, the value of the alkaline titration of standard lactic, formic, acetic, and pyruvic acids was equal to the amount analyzed with the carboxylic acid analyzer. The results indicated that these two streptococci produced not only these carboxylic acids but also other acid(s), possibly non carboxylic acid(s), during their sugar metabolism. PMID- 2910955 TI - Characterization of one phenotype of human periodontal granulation-tissue fibroblasts. AB - Human granulation-tissue fibroblasts were cultured from oral chronic inflammatory lesions and compared with fibroblasts of healthy gingival connective tissue with respect to cell-surface sialoglycoproteins, and the synthesis of extracellular matrix components. Granulation-tissue fibroblasts exhibited a slower growth rate and larger size than their controls. Their cell-surface sialoglycoproteins resembled those of the control cells, except that the relative amount of glycoproteins in the 140-kd region was lower. The ratio of mRNAs for pro alpha l (I) and pro alpha l (III) collagen chains was decreased in granulation-tissue fibroblasts, although electrophoretic fractionation of the proteins did not reveal consistent differences in type I/type III collagen ratio. Granulation tissue fibroblasts secreted into the culture medium a dermatan sulfate proteoglycan with a lower molecular weight. After digestion with chondroitinase ABC, the molecular weight of the core protein appeared to be identical with that of the control fibroblasts, suggesting a difference in the glycosylation of the core protein. These results support the theory that granulation-tissue fibroblasts represent a distinct phenotype of fibroblastic cells. PMID- 2910956 TI - Electron probe micro-analysis for subsurface demineralization and remineralization of dental enamel. AB - A quantitative study of fluoride distribution profile changes in dental enamel was conducted by means of electron probe micro-analysis (EPMA). Fluoride deposited hydroxyapatite powders were chosen as fluoride standards, and analytical conditions were optimized. The lower limit of detection for fluoride was estimated to be 270 ppm, with an accelerating voltage of 5 kV, a specimen current of 40 nA, and a counting time of 40 seconds. Fluoride profiles in fluoride-treated dental enamel, which exhibited intact surface layers and subsurface demineralization, were determined. The results were also compared with those of an acid-abrasion method, and reasonable consistency was found between these two methods, although the acid-abrasion procedure yielded a slightly lower fluoride content in the initial layers, followed by a higher content of fluoride in the deeper layers. The precision of fluoride profile data obtained from EPMA permits further studies to be conducted on the kinetics of subsurface demineralization and intact surface layer formation ("white spot" formation) which is observed during the acid challenge of dental enamel. PMID- 2910957 TI - Quantitative study of fluoride transport during subsurface dissolution of dental enamel. AB - Previous studies using bovine dental enamel as a model have shown that surface and subsurface dissolution of enamel may be governed by micro-environmental solution conditions. We have now investigated the demineralization phenomenon more rigorously with the primary objective of developing a method for deducing solution species concentration profiles as a function of time from appropriate experimental data. More specifically, in this report, a model-independent method is described for determination of the pore solution fluoride gradients in bovine enamel during subsurface demineralization. Microradiography was used to determine the mineral density profiles, and an electron microprobe technique to determine total fluoride (F) profiles associated with the enamel. In each case, matched sections of bovine enamel were exposed to partially saturated acetate buffers at pH = 4.5 containing 0.5 ppm F for various periods of time (from six to 24 hours). The treated enamel was found to have an intact surface layer and subsurface demineralization. The extent of the demineralization and the depths of the lesions increased with time in all cases. The data were first used to calculate (a) the total F gradients in the enamel at various times, and (b) the local uptake rate of F as a function of time and position. Then, by manipulation of the equations describing the uptake and transport of F, we calculated the pore diffusion rate of F and the micro-environmental solution F concentration in the aqueous pores as a function of time and of distance from the enamel surface. It was also possible to calculate an intrinsic F diffusion coefficient in the pores, which was about 1.0 X 10(-5) cm2/sec, in good agreement with reported values. 14C sucrose uptake and release experiments with identically prepared demineralized enamel sections were also conducted to provide an independent check on the assumed dependence of porosity on mineral density. The results of this investigation, especially the outcomes relative to this new method for determination of pore solution F gradients during acid attack of the dental enamel, should be valuable in future studies of the mechanism(s) of the action of F in inhibiting dental enamel demineralization. PMID- 2910958 TI - Jaw pain and stiffness levels after repeated maximum voluntary clenching. AB - Ten normal male volunteers performed six maximum voluntary isometric jaw-closing muscle contractions within an 80-minute experimental period. Each individual contraction was sustained until maximum pain tolerance was reached. Before and one, two, three, and seven days after the experiment, the following measures were made: (1) superficial masseter and anterior temporalis muscle tenderness (pain threshold), (2) jaw movement (opening and lateral excursion), and (3) current pain level for the right and left sides of the jaw. In this study, measures of current jaw pain, muscle pain threshold, maximum active opening, and maximum lateral excursions showed no significant post-experimental changes. These results challenge the idea that sustained isometric clenching in healthy male subjects could be used as a model for chronic or even subacute muscle pain, as has been suggested by previous investigators. PMID- 2910960 TI - 66th AADS annual session. American Association of Dental Schools. San Francisco, California, March 12-15, 1989. Abstracts of educational research and new educational programs presentations. PMID- 2910959 TI - Influence of milk and food on fluoride bioavailability from NaF and Na2FPO3 in man. AB - Aqueous solutions of NaF and sodium monofluorophosphate (MFP) were given to fasting young adults in an intra-individual cross-over study. Plasma fluoride (F) levels were measured by use of a F-ion-sensitive electrode, and eight-hour profiles of F concentrations in plasma were determined. F availability and pharmacokinetic data were identical for both substances. Furthermore, the same subjects were given tablets containing 2 mg F, either as NaF or as MFP, under different experimental regimens: (a) on a fasting stomach, (b) together with milk, or (c) together with breakfast and milk. Equal F availabilities were observed for both substances. Plasma peak levels were reduced when the tablets were taken together with food. Intake of milk reduced F availability by 30% compared with the fasting stomach experiment; this effect was abolished when milk was taken as part of the breakfast. It is suggested that formation of Ca salts and entrapment of F in coagulation products of milk are important factors causing reduction of F availability, and that prolonged stay of the chyme after concomitant ingestion of food allows F to become liberated from bound forms and coagulation products by digestion processes. PMID- 2910961 TI - Liposuction under local anesthesia. PMID- 2910963 TI - Narrow versus wide margins in malignant melanoma. AB - Although wide surgical excision is the accepted treatment for thin malignant melanomas, there is reason to believe that narrower margins may be adequate. A randomized prospective study to assess the efficacy of narrow excision (excision with 1-cm margins) for primary melanomas no thicker than 2 mm was conducted at the National Institute of Health in Milan, Italy, and five other countries. Narrow excision was performed in 305 patients and wide excision (margins of 3 cm or more) in 307 patients. The major prognostic criteria were well balanced in the two groups. The mean thickness of the melanomas was 0.99 mm in the narrow excision group and 1.02 mm in the wide-excision group. The subsequent development of metastatic disease involving regional nodes and distant organs was not different in the two groups (4.6% and 2.3%, respectively, in the narrow-excision group as compared with 6.5% and 2.6% in the wide-excision group). Disease-free survival rates and overall survival rates (mean follow-up period was 55 months) were also similar in the two groups. Only three patients had a local recurrence as a first relapse. All had undergone narrow excision, and each had a primary melanoma with a thickness of 1 mm or greater. PMID- 2910962 TI - Cystic tumors of the neck. PMID- 2910964 TI - Topical minoxidil used before and after hair transplantation. AB - A 2% solution of topical minoxidil was applied on the recipient bald scalp of 16 patients aged 25 to 52 years with Hamilton classifications of androgenetic alopecia from III to VI. Therapy was begun 4 weeks before surgery, was interrupted for 3 weeks, and was started again and continued for 3 months. Four millimeter donor grafts were inserted into 3.5-mm recipient sites. Follow-up utilizing macrophotography was done for 3 months on 4 grafts near a tattooed area. In 71% of the 64 grafts, partial or total hair is still growing without the shedding that usually occurs 2-4 weeks after transplantation. Topical minoxidil seems to be an adjunct for a better evolution of grafts after hair transplantation surgery. PMID- 2910965 TI - Scarring following herpes simplex infection of postsurgical cutaneous sites. AB - Herpes simplex type 1 produces a perilabial vesicular eruption that normally resolves without scarring. Three cases of herpetic infection associated with different dermatologic surgical procedures are presented. Those procedures involving reduction of cutaneous macrovascular blood supply via undermining or flap creation were followed by clinical scarring. None of the recognized etiologies of tissue compromise (bacterial infection, tension, host vascular disease, excessive inflammation, or edema) could be identified. It is speculated that in the immunocompetent host, small vessel injury secondary to herpes simplex may eventuate in scarring if the subdermal vascular network is significantly compromised. Prophylactic oral acyclovir may be useful in select instances where tissue blood supply is judged clinically tenuous and the frequency of herpetic infection at the surgical site judged worrisome. PMID- 2910966 TI - Treatment of chromomycosis by cryosurgery with liquid nitrogen: a report on eleven cases. AB - Cryosurgery with liquid nitrogen was used to treat 11 cases of chromomycosis, 5 with localized lesions and 6 with generalized ones. Freezing time varied from 30 seconds to 4 minutes and the number of cycles from 1 to more than 40. All 5 cases with localized lesions responded extremely well to treatment, with no relapse for up to 53 months. Three patients with generalized lesions attained clinical and mycologic remission for up to 26 months, while 3 had significant improvement without cure. Cryosurgery with liquid nitrogen is therefore an effective treatment for chromomycosis, especially for cases presenting with localized lesions. PMID- 2910967 TI - The perialar arc rotation skin flap. AB - The perialar arc rotation skin flap is an excellent reconstructive option for defects of the lateral nose that do not significantly involve the ala. Design of this new skin flap and potential intraoperative problems are discussed. Use of microlipoextraction for some "trap door" skin flap deformities is presented. PMID- 2910968 TI - Verrucous hemangioma and angiokeratoma circumscriptum: clinical and histologic differential characteristics. AB - It is important, from a prognostic and therapeutic point of view, to make a correct diagnosis between verrucous hemangioma (VH) and angiokeratoma circumscriptum. The former needs a large and deep exeresis, while the latter responds to the common means of physical therapy. Two cases of verrucous hemangioma are reported that have allowed us to review the clinical and histologic differential characteristics of the two forms. PMID- 2910969 TI - Giving due credit for the design of a hemostat for hair transplantation. PMID- 2910970 TI - Hearing impairment as a determinant of function in the elderly. AB - This clinical, practice-based study explores the research question: Is there a relationship between hearing loss and functional disturbance in elderly patients? We analyzed the impact of hearing impairment on 153 patients over 65 years of age screened in primary care practice. Functional and psychosocial impairment were measured using the Sickness Impact Profile (SIP), a standardized measure for assessing sickness related dysfunction. Hearing level was determined with pure tone audiometry. Multiple linear regression was used to adjust for patient case mix differences and other clinical variables. After adjustment, a 10 dB increase in hearing loss was found to result in a 2.8 point increase in Physical SIP scores (95% confidence interval = 1.8-3.8), a 2.0 point increase in psychosocial SIP scores (95% confidence interval = 0.8-3.2) and a 1.3 point increase in overall SIP scores (95% confidence interval = 0.1-2.5). Poor hearing was associated with higher SIP scores and increased dysfunction. Thus, hearing impairment is an important determinant of function in the elderly. PMID- 2910971 TI - Clinical significance of sleep-disordered breathing in Alzheimer's disease. Preliminary data. AB - In a study of 15 probable Alzheimer's patients and 12 healthy elderly control subjects, Alzheimer's patients had a significantly higher apnea index (patients versus controls, mean +/- SD: 6.3 +/- 6.6 vs 1.8 +/- 2.7, P less than .05) and greater maximal duration of apnea (patients versus controls, median: 50.0 vs 28.5 seconds, P less than .001), but no significant increase in oxyhemoglobin desaturation compared with controls. (The accepted normal threshold for abnormality is an apnea index more than 5.) Although three of seven psychometric tests (odd-even, category retrieval, face-hand test) showed diurnal effects on one or more of their subscores, with Alzheimer's patients having significantly poorer scores at the AM than at PM testing, overnight change scores in the psychometric tests were not significantly correlated with severity of sleep disordered breathing. Further, only 18.1% of the disruptive (ie, requiring intervention) nocturnal behaviors of the Alzheimer's patients were temporally linked to sleep-disordered breathing. The current data suggest that sleep disordered breathing in nonmedicated Alzheimer's patients is relatively mild and is not a predictor of either overnight mental status changes, of disruptive nocturnal behaviors, or of daytime behavioral fluctuations. Additional studies of more severely demented patients and possibly of sleeping pill effects would be useful in further evaluating the role of sleep apnea in Alzheimer behavioral changes. PMID- 2910972 TI - Correlation of estimated renal function parameters versus 24-hour creatinine clearance in ambulatory elderly. AB - This study evaluates the correlation between estimated renal function parameters (ie, creatinine clearance by the Cockcroft-Gault and Lott-Hayton formulas, serum creatinine and blood urea nitrogen) and 24-hour creatinine clearance in 15 young and 15 elderly subjects. Correlation coefficients (r) for the elderly group comparing Cockcroft-Gault and Lott-Hayton against 24-hour creatinine clearance were 0.73 (P less than .005) and 0.60 (P less than .02) respectively, and r for the young subjects were 0.37 (P greater than .05) and 0.57 (P less than .05), respectively. In 13 elderly subjects with creatinine clearance of 60 mL/minute or less, four (31%) had blood urea nitrogen of 20 mg/dL or less and 13 (100%) had serum creatinine between 1.0-1.5 mg/dL. We conclude that the formulas of Cockcroft-Gault and Lott-Hayton are valid in ambulatory elderly patients who are functionally independent without severe underlying disease, have normal body weight and are not on medication affecting renal function. Furthermore, in this select elderly population, an apparently normal serum creatinine (1.0-1.5 mg/dL) and blood urea nitrogen (20 mg/dL or less) may frequently represent a 24-hour creatinine clearance of 60 mL/minute or less. PMID- 2910973 TI - Acute confusion in elderly medical patients. AB - The acute confusional state (delirium) is a common presentation for a wide variety of medical conditions in the elderly. This paper reports a prospective study of acute confusion in elderly people admitted to general medical services in two acute care hospitals in Edmonton, Alberta. Eighty patients were studied, ranging in age from 65-91. Acute confusion was seen in one-fourth of these patients, who tended to be older, more ill, more likely to have chronic cognitive impairment and a higher mortality rate. In patients admitted with confusion, infection and congestive heart failure predominated. In those who developed confusion after hospitalization, iatrogenic disease was more common. Confusion was a sensitive sign of physical illness, and its resolution accompanied recovery. A diagnosis of the cause of the confusion state could be made in 22 of 24 cases. These findings support the aggressive investigation and treatment of acute confusion in the elderly. PMID- 2910974 TI - Survival after cancer surgery of elderly patients in New Mexico, 1969-1982. AB - To examine the effects of advancing age, sex, and ethnicity on estimated 30-day survival after surgery for cancer, we reviewed population-based data on 16,130 cancer cases collected by the New Mexico Tumor Registry from 1969-1982. For surgery at most sites, mortality increased with increasing age. The highest mortality was observed for sites requiring laparotomy or thoracotomy. Sex and ethnicity (Hispanic versus non-Hispanic white) had little effect on short-term survival. Comparison of short-term survival for two time periods, 1969-1975 and 1976-1982, showed a strong trend of improving survival for many sites. PMID- 2910975 TI - Penile encrustation due to a condom catheter. AB - We report a 68-year-old man with penile encrustation caused by a condom catheter used for urinary incontinence. High-resolution x-ray crystallographic analysis of the encrustation revealed struvite [MgNH4PO4.6H2O] and apatite [Ca5(PO4)3(OH)]. Physicians should be aware that penile encrustation may occur as a complication of condom catheter use. The problem of encrustation is discussed. A brief review of condom catheter complications is presented. PMID- 2910976 TI - Occult temporal arteritis: a cause of complete blindness. PMID- 2910977 TI - Re: "Decisions to leave home". PMID- 2910978 TI - Acute myocardial infarction in the elderly. PMID- 2910979 TI - Postcard reminders and influenza vaccination. PMID- 2910980 TI - Corrections re: Chemstrip LN. PMID- 2910981 TI - Direct assessment of ADL in Alzheimer's disease. PMID- 2910982 TI - Asymptomatic bacteriuria and incontinence. PMID- 2910983 TI - Message to biologists from the GSA taskforce on minority issues in gerontology. PMID- 2910984 TI - Serum androgen levels in senescent Cr1:CD-1 (ICR)BR mice: effects of castration and testosterone treatment. AB - Serum levels of dehydroepiandrosterone, androstenedione, testosterone, and dihydrotestosterone were measured in intact, orchiectomized and orchiectomized androgen-treated CD-1 mice. Although dehydroepiandrosterone was not detectable in the serum of old mice, approximately half of the very substantial serum concentration of this hormone found in the mature mice appeared to be of adrenal origin. In contrast to dehydroepiandrosterone, serum levels of testosterone and, when detectable, the other androgens, were the same in mature and senescent intact males. Serum levels responded similarly to castration and testosterone replacement. Seminal vesicle weights reflected the similar serum androgen levels found in both age groups. The results indicate that there is neither an age associated decline in the serum concentration of testosterone nor an apparent alteration in the hepatic and/or peripheral metabolism of testosterone in aging CD-1 male mice. PMID- 2910985 TI - Evidence for the glycation hypothesis of aging from the food-restricted rodent model. AB - Glucose has been proposed as a mediator of aging processes by means of glycation reactions resulting in advanced glycosylation end-products, thereby altering protein and DNA function. Testing this provocative concept has a high priority in gerontologic research. In this study, food restriction of rats--a procedure which markedly retards aging processes--was used to test the glycation hypothesis. Food restricted rats were found to have a sustained plasma glucose concentration and percentage glycosylation of hemoglobin significantly lower than those of ad libitum fed rats. These findings are consistent with and provide support for the glycation hypothesis. PMID- 2910986 TI - Small intestinal crypt cell proliferation rates are increased in senescent rats. AB - Our previous studies implied that intestinal epithelial cell replication might be increased in senescent rats. Duodenal, jejunal, and ileal crypt cell production rates (CCPR) were measured in 3-4-mo and 26-28-mo female fed control, 3-day starved and 1-day refed, and in 4-5-mo and 26-28-mo male fed Fischer rats, using the vincristine-induced metaphase arrest technique. Fed aging rats had greater proximal intestinal crypt cell numbers which fell less during starvation than those of young controls. Metaphase accumulation also was higher in aging rat duodenum and jejunum, and CCPR were 30-100% more than in young rats. Starvation reduced CCPR by more than 40% in the duodenum of young, but only by 10% in older animals. Crypt proliferative patterns demonstrated a broadened proliferative zone in aging rats. These combined results directly demonstrate that small intestinal cell production is enhanced in senescent rats and that the nutritional controls of proliferation are blunted. PMID- 2910987 TI - Health status of aged minorities: directions for clinical research. PMID- 2910988 TI - Sleep fragmentation in patients from a nursing home. AB - Institutionalized elderly persons are said to have very disturbed sleep, yet few studies have collected empirical data on the sleep of these patients. We recorded sleep in 200 patients (131 females and 69 males; mean age = 81.9 years, SD = 8.6) in a skilled nursing facility. A modified Respitrace-Medilog portable recording system was used. In recordings averaging 15.4 hours, the patients were asleep for 7 hours, 58 minutes and awake for 7 hours, 28 minutes. To obtain that amount of sleep, the patients spent an extended time in bed during the day, for they averaged no more than 39.5 minutes of sleep per hour in any hour of the night, and 50% woke up at least 2 to 3 times per hour. In summary, although nursing home patients slept on average only one hour longer than independently living elderly, they had to spend substantially more time in bed to obtain the same amount of sleep. PMID- 2910989 TI - Effects of aging and beta-adrenergic-blockade on standing-induced QT/QS2 changes. AB - In order to evaluate whether the changes in the electrical systole/electromechanical systole ratio (QT/QS2) may reflect the effects of beta adrenergic stimulation on the heart, we studied the variations of this ratio induced by active standing. We studied 45 healthy volunteers aged 15 to 82 years, subdivided into three groups; Group 1 (mean age 22 +/- 4 years), Group 2 (mean age 44 +/- 6 years), and Group 3 (mean age 74 +/- 6 years). Fifteen subjects repeated the test after propranolol administration (0.1 mg/kg iv). Resting QT/QS2 ratio increased slightly, but not significantly, with age. Upright position significantly increased QT/QS2 ratio in all groups. Changes in heart rate (r = .43), electromechanical systole (r = .55) and QT/QS2 were significantly correlated with age. Propranolol prevented the increase in QT/QS2 ratio induced by active standing. Therefore, QT/QS2 changes induced by standing are correlated with age and are inhibited or reduced by beta-blockade. QT/QS2 changes can be used to monitor adrenergic activity, even if their value is limited by the overlapping responses of the individual cases. PMID- 2910990 TI - Impaired sympathetic nervous system response to cognitive effort in early Alzheimer's disease. AB - Sympathetic nervous system responses to a cognitive challenge and a physiologic stimulus (upright posture) were compared in 10 patients with early Alzheimer's Disease and a group of healthy older adults. Plasma catecholamine and cardiovascular responses to upright posture were similar in the two groups. However, sympathetic activation during mental effort was impaired in the patient group; this difference did not appear to be attributable to motivational factors. Alzheimer's Disease is associated with a defect in sympathetic nervous system function that is specifically linked to cognitive effort and appears early in the course of the disease. PMID- 2910991 TI - Race, ethnicity, and psychological theory and research. PMID- 2910992 TI - Age-related differences in three-dimensional spatial memory. AB - This study focused on understanding age differences in spatial memory within a framework relating stimulus qualities to performance. It was hypothesized that elderly adults' spatial memory would be more disadvantaged, relative to young adults, with abstract, meaningless objects than with everyday objects. The study examined differences in memory for the horizontal, vertical, and depth dimensional planes of space in a 4 x 4 x 4 plexiglass cube. College students and community-dwelling adults studied and later reconstructed a three-dimensional arrangement of common or abstract objects located in a compartmentalized cube so that relocation errors could be independently measured within the horizontal, vertical, and depth dimensions. The principal findings were that (a) the magnitude of object displacement in the relocation task was greater for older adults; (b) young and elderly adults differed primarily in terms of large rather than small displacement errors; (c) the locations of meaningless items were more difficult to remember for both age groups; and (d) displacement errors in the vertical dimension were greater than the horizontal and depth dimensions, although this effect was only significant with meaningful items. PMID- 2910993 TI - Age differences in body consciousness. AB - Physical changes associated with the aging process have both private and public components, and this study investigated the degree to which elderly persons attend to these changes. Sixty subjects, elderly (n = 30) and young (n = 30), equated in terms of physical health, education, and depression, were compared on measures of private body consciousness, public body consciousness, and body competence. Results indicated that healthy elderly persons are more conscious of their external physical appearance and are more positive in their self evaluations of body competence than are young subjects. PMID- 2910994 TI - A longitudinal study of neuropsychological performance by hypertensives and normotensives: a third measurement point. AB - The neuropsychological test performance of hypertensive and normotensive subjects was compared at three times of measurement over a 10-year period. The tests used were among those that are most sensitive to brain impairment in the Halstead Reitan battery. In addition to individual test measures, a widely used clinical index of battery-wide performance--the Average Impairment Rating (AIR)--was used. Hypertensives exhibited lower mean levels of performance on the AIR at all times of measurement. However, the Blood Pressure Group x Time of Measurement interactions were not statistically significant, indicating that hypertensives and normotensives did not exhibit a differential rate of change (decline or improvement) over time. Hypertensives also performed more poorly for a measure of learning set formation (categories test) and two tests of memory for forms experienced by touch only (tactile perception memory and localization tests). However, Blood Pressure x Time of Measurement interactions were not observed for these measures. PMID- 2910995 TI - Behavioral treatments and pharmacotherapy: acceptability ratings for elderly individuals. AB - Two studies compared acceptability ratings of a positive behavioral treatment (differential reinforcement of incompatible behavior), a mildly aversive behavioral procedure (time-out), and pharmacotherapy used for older adults. In Study 1, college students were presented with descriptions and asked to rate the treatments of case clients who were depicted as either young or elderly, cognitively intact or impaired, and engaging in physical aggression, verbal abuse, or noncompliance. The respondents in Study 2 were adults aged 30-49, and senior center participants aged greater than or equal to 60 who were asked to evaluate only the scenarios involving elderly case clients. The Treatment Evaluation Inventory and a Semantic Differential Scale were used to assess acceptability. Results showed that: (a) college students rated medication higher for elderly case clients, and the behavioral treatments higher when applied with children; (b) adult and elderly respondents assigned the highest acceptability ratings to the differential reinforcement of incompatible behavior procedure, followed by medication and time-out; (c) all respondents assigned differential acceptability ratings depending on the behavior problem described, with more severe problems generally warranting more invasive treatments; (d) acceptability ratings of treatments did not differ as a function of cognitive capacity of case clients. Implications of these results for clinicians employing behavioral interventions with elderly clients are discussed, and suggestions are made for additional research. PMID- 2910996 TI - Age differences in processing expository and narrative text. AB - A dual-task procedure was used to examine the effects of text genre on prose processing, comprehension, and recall in 20 young (18-33 years) and 20 old (65-80 years) adults. Response latencies on a secondary task provided an index of cognitive capacity used in reading narrative and expository passages. Both groups recalled more of narratives than of expository passages, although old subjects recalled less than young. Also, the narrative protocols of both age groups showed a greater difference for recall of main ideas as compared to details. Age differences in the pattern of text genre effects were found on measures of comprehension, capacity utilization, and processing efficiency. It appears that the narrative genre facilitated most measures of performance and partially compensated for some limitations in the older group. PMID- 2910997 TI - Reexamining the double jeopardy to health thesis. AB - The purposes of this article are twofold: (a) to clarify the evaluation of the double jeopardy thesis and (b) to evaluate two apparently contradictory sets of results on the double jeopardy to health derived from the same data (National Council on the Aging, 1975). The results offer no support for the double jeopardy thesis based on a subjective assessment of health problems. Both logistic regression analysis and multiple discriminant analysis were used to estimate the relationships among the variables considered. PMID- 2910998 TI - The health impact of living with a cognitively impaired elderly spouse: depressive symptoms and social functioning. AB - The purpose of this study was to identify the social and psychological consequences of living with a cognitively impaired spouse among community dwelling elderly individuals. The study sample consisted of 318 spouse pairs drawn from a representative sample of noninstitutionalized elderly individuals. Our principal findings were that: (a) Cognitive impairment in wives is significantly (p less than .05) associated with depressive symptomatology in husbands, whereas cognitive impairment in husbands is only weakly (p greater than .20) associated with depressive symptomatology in wives; (b) Decreased participation in social/leisure activities is selectively related to spouses' level of cognitive functioning among both men and women; (c) The relationship between wives' cognitive impairment and husbands' depressive symptoms is influenced by perceived availability of financial support from friends and relatives, but not by ADL limitations in wives, lack of emotional or instrumental support from wives, household responsibilities among husbands, or lack of participation in social/leisure activities in husbands. PMID- 2910999 TI - Minority aging research: opportunity and challenge. PMID- 2911000 TI - Orderly endings: do men know when they will retire? AB - In order to describe the subjective (as opposed to the statistical) predictability of the retirement event, this study examined the timing of men's retirement relative to their own expectations. On-time and off-time retirements were assessed in a panel of older workers, participants in the VA Normative Aging Study, who were surveyed about work and retirement in 1978, 1981, and 1984. Over spans of two years, 66 percent of workers accurately predicted their eventual date of retirement (+/- 1 year), and 40 percent were exact to within three months. However, approximately one-third of workers did not accurately foresee their date of retirement, having either unfulfilled plans or unanticipated retirements. From a life course perspective, we interpret retirement as an orderly event when two-thirds of a sample can retire as planned. From a practical perspective (e.g., an interest in program development or research design), retirement is not orderly enough when one-third of exits are unscheduled. PMID- 2911001 TI - Relative contributions of help by employed and nonemployed sisters to their elderly parents. AB - The relationship between daughters' employment status and involvement in the provision of services to old parents was examined using information collected from 50 pairs of sisters whose employment status differed. The Wilcoxon matched pairs, signed-ranks test was used to assess whether employment status affected perceptions of parents' needs, relative contributions to parents, and relative contributions when parents' health status was poorer. Nonemployed sisters contributed relatively more tangible services than their employed sisters when parents' health status was poorer. Qualitative analysis of the interviews indicated that although nonemployed sisters usually took disproportionate responsibility for medical appointments and day-time emergencies and care, employed sisters were expected to contribute in other ways. That the significance of individual attributes of family members makes sense only within the family context is stressed. PMID- 2911002 TI - Stress and religious involvement among older blacks. AB - We conducted this study in a nationwide sample of older Black Americans to determine whether religious involvement helps to reduce the negative impact of stressful life events. The major outcome measures were self-esteem and feelings of personal control. Three models of the stress process were evaluated empirically: the suppressor, moderator, and distress-deterrent models. The data provided support for the distress-deterrent model only. The findings from this model indicated that although life stress to erode feelings of self-worth and mastery, these negative effects were offset or counterbalanced by increased religious involvement. PMID- 2911003 TI - Rapid localization of carbon 14-labeled molecules in biological samples by ion mass microscopy. AB - We report here on the ability of secondary ion mass spectrometry (SIMS) to provide rapid imaging of the intracellular distribution of 14C-labeled molecules. The validity of this method, using mass discrimination of carbon 14 atoms, was assessed by imaging the distribution of two molecules of well-known metabolism, [14C]-thymidine and [14C]-uridine, incorporated by human fibroblasts in culture. As expected, 14C ion images showed the presence of [14C]-thymidine in the nucleus of dividing cells, whereas [14C]-uridine was present in the cytoplasm as well as the nucleus of all cells, with a large concentration in the nucleoli. The time required to obtain the distribution images with the SMI 300 microscope was less than 6 min, whereas microautoradiography, the classical method for mapping the tissue distribution of 14C-labeled molecules, usually requires exposure times of several months. Secondary ion mass spectrometry using in situ mass discrimination is proposed here as a very sensitive method which permits rapid imaging of the subcellular distribution of molecules labeled with carbon 14. PMID- 2911004 TI - Cytochemical demonstration of increased phospholipid content in cell membranes in chlorphentermine-induced phospholipidosis. AB - We recently introduced a novel cytochemical approach to high-resolution cytochemistry of phospholipids in biological tissues. The technique consists of adsorption of bee venom phospholipase A2 to colloidal gold particles (PLA2-gold complex) and subsequent application of this complex for localization of the enzyme substrate, i.e., glycerophospholipids. In the present study, this technique was applied at the post-embedding level, in both light (LM) and transmission electron microscopy (TEM), to investigate drug-induced phospholipidosis, an experimental disorder in which the lysosomal catabolism of phospholipids is inhibited. Rats received one week of daily treatment (40 mg IP/kg) with chlorphentermine (CP), a cationic amphiphilic drug known to induce phospholipidosis in several tissues. Glutaraldehyde- and osmium-fixed lung and kidney tissues from both treated and control animals, were embedded in Epon and sections processed for labeling by PLA2-gold. In CP-treated specimens the presence of large osmiophilic inclusions in several cell types of lung parenchyma and kidney cortex confirmed the onset of phospholipidosis. These inclusions were densely labeled by PLA2-gold at both LM and TEM levels. Two general types of abnormal inclusions were distinguished on the basis of their ultrastructure and labeling pattern by PLA2-gold, suggesting different content or configuration of phospholipids. Moreover, quantitative evaluation of labeling density over various membrane compartments in lung alveolar cells evidenced significantly increased phospholipid content after CP treatment. In type II pneumocytes, such increases were measured in membranes of the RER, Golgi complex, outer and inner nuclear envelope, and the basolateral and apical domains of the plasma membrane. In capillary endothelial cells, the basal and luminal domains of the plasma membrane also showed an increase in labeling density. These results further demonstrate the potential usefulness of the PLA2-gold technique for in situ ultrastructural localization of phospholipids in normal and pathological tissues. PMID- 2911005 TI - Intracellular binding of wheat germ agglutinin by Golgi complexes, phagosomes, and lysosomes of Paramecium multimicronucleatum. AB - The compartments of the Paramecium digestive system were investigated with wheat germ agglutinin (WGA). By use of cryosectioning or Lowicryl K4M embedding combined with pulse-chase studies and WGA-gold labeling, WGA binding sites were located on membranes of the phagosome-lysosome system, including all four stages of digestive vacuoles, the discoidal vesicles, acidosomes, and lysosomes. In addition, the contents of lysosomes, cisternae at the trans face of Golgi stacks, and coated and uncoated blebs and vesicles at the putative trans Golgi network bind to WGA. Crystal-containing vacuoles characteristic of mid-log to stationary phase cultures are enclosed by heavily labeled membranes. Alveoli underlying the plasma membrane sometimes contain binding sites, particularly on their outer membranes. Ciliary membranes previously shown to be labeled with WGA-FITC are negative in frozen thin and Lowicryl K4M sections. The presence of WGA binding sites on the trans face of the Golgi stack is the first indication in ciliated protozoa, such as Paramecium, of probable Golgi complex involvement in glycosylation similar to that in higher organisms. WGA-labeled coated vesicles in the endoplasm apparently lose their coats and coalesce to form lysosomes. Our study shows that WGA can be used as a specific intracellular marker of all digestive system membranes and of lysosomal content. These results support and extend our published scheme of membrane flow and recycling in Paramecium by providing another means of demonstrating membrane relationships. PMID- 2911006 TI - Comparison of fixatives for maximal retention of radiolabeled glycoconjugates for autoradiography, including use of sodium sulfate to release unincorporated [35S] sulfate. AB - Previous studies have used [35S]-sulfate as a specific marker to autoradiographically localize sulfated glycosaminoglycans, proteoglycans, and glycoproteins. Embryonic chicks were labeled with [35S]-sulfate, followed by previously reported routine fixation and processing techniques. Subsequent processing revealed loss of radiolabeled macromolecules and retention of unincorporated label in the tissue, using these procedures. Biochemical analysis after various fixation and processing procedures demonstrated that an additional agent, such as cetylpyridinium chloride, was necessary in the fixative to retain the highly aqueous soluble sulfated macromolecular components. Molecular sieve chromatography was used to monitor digestate solutions for the identity of glycosaminoglycans and proteoglycans as indicated by selective enzymatic removal. Retained unincorporated [35S]-sulfate could be completely removed by rinsing the tissue in dehydration solutions containing exogenous sodium sulfate. This new procedure ensures the quantitative retention of sulfate labeled macromolecules in fixed tissue with the complete removal of unincorporated radiotracer, both of which are necessary for meaningful autoradiography. PMID- 2911007 TI - Ultracytochemistry of calmodulin binding sites in myocardial cells by staining of frozen thin sections with colloidal gold-labeled calmodulin. AB - Calmodulin (CaM) has been implicated as a multifunctional regulator of Ca2+ in the cytoplasm of cells. We have recently introduced biologically active colloidal gold-labeled CaM as a marker for identifying potential CaM binding sites (unoccupied by endogenous CaM at the time of fixation) by electron microscopy and have stained frozen thin sections of rat cardiac muscle with this conjugate. In the presence of Ca2+, gold particles indicating CaM binding sites were found localized on the sarcoplasmic reticulum, mitochondria, and gap junctions. Control tissue sections treated with EGTA or exposed to excess amounts of unlabeled native CaM before staining showed no binding. We believe that cytochemistry of potential CaM binding sites revealed by staining with labeled exogenous CaM is useful in correlating known biochemical reactions of CaM with particular cell activities. PMID- 2911008 TI - Demonstration of immunoreactive sites on cartilage after in vivo administration of biotinylated anti-type II collagen antibodies. AB - Administration of biotinylated monoclonal antibodies provides the basis of a simple technique for identifying immunoreactive sites in vivo. Biotinylated anti type II collagen antibodies were injected intraperitoneally into normal DBA/1 mice. The mice were sacrificed after 96 hr and the front paws removed and decalcified to allow tissue sectioning before snap-freezing. Binding of antibodies in vivo was visualized with affinity cytochemical staining using avidin-biotin-peroxidase complexes. Specific binding of antibodies to cartilaginous structures was seen after injection of 20-500 micrograms biotinylated monoclonal or polyclonal anti-type II collagen antibodies, but not after injection of a biotinylated control antibody. This technique should further the detection and localization studies of tissue components involved in the dynamics of physiological and pathological processes. PMID- 2911009 TI - The xid mutation affects hemopoiesis in long term cultures of murine bone marrow. AB - Cells of the humoral immune system are particularly affected by a mutation at the X chromosome linked immunodeficiency disease (xid)locus. Although B cells are made in normal numbers, they fail to become phenotypically and functionally diverse. Consequently, poor antibody responses are mounted to certain types of Ag. There have been some indications that other types of hemopoietic cells may be influenced by the mutation and development of the humoral immune system is unusually dependent on the presence of T lymphocytes. We now describe an analysis of the lympho-hemopoietic environment studied with long term bone marrow cultures. Contrary to expectations, cultures initiated with cells from homozygous female or hemizygous male mice with the mutant allele established more quickly than normal. The accelerated initial growth pattern was clearly linked to the xid mutation. Artificial mixtures of marrow exhibited intermediate growth kinetics. Experiments with H-2 congenic and T6 chromosome marked cells did not reveal an intrinsic dominance of growth in nonadherent xid cells. Similar results were obtained with culture conditions which favored production of myeloid or lymphoid cells. These findings would be consistent with subtle changes in the bone marrow microenvironment resulting from the xid mutation. The pedigree of the mouse strains had a significant influence on lymphopoiesis in long term bone marrow cultures. Lymphocytes of BALB/c origin dominated over CBA/H background cells in cultures established from mixtures of the two, but this did not correlate with any functional deficiency in CBA/H stromal cells. In fact, establishment of an adherent layer was a rate-limiting step in initiating long term cultures and this could be achieved with a low dose inoculum of CBA/H marrow. Even more dramatic effects were found in hemopoietic cells from doubly defective C3H.nu/nu-xid mice. The bone marrow of these athymic animals contained normal numbers of granulocyte/macrophage progenitors. However, lymphoid cultures could not be reproducibly established with their cells and myelopoiesis was never observed in vitro. The relatively simple conditions which pertain in culture make it possible to appreciate effects of mutations and pedigree on hemopoiesis which are unremarkable in intact animals. PMID- 2911010 TI - Two steps in the intracellular transport of IgD are sensitive to energy depletion. AB - The secretory pathway of murine IgD can be dissected by the use of carbonylcyanide m-chlorophenylhydrazone (CCCP), which inhibits two distinct steps of intracellular transport. The newly synthesized IgD that accumulates at the first step contains high mannose type oligosaccharides which are partially trimmed. The IgD arrested at this step is less processed than the IgD arrested by treatment with monensin. The properties of this biosynthetic intermediate are consistent with inhibition of Ig passage from the endoplasmic reticulum to the Golgi complex. A second CCCP-sensitive step exists in the biosynthesis of IgD, and is characterized by delta-chains that are resistant to endoglycosidase H and contain galactose. This indicates that this second step occurs during or after the passage through the trans-Golgi compartment. The galactose-containing oligosaccharides of the delta-chains arrested at this step do not contain fucose (as do mature, secreted delta-chains). Fucosylation is not inhibited by CCCP, nor is the secretion of fucose-containing delta-chains. These results show that terminal sugars are added to secretory IgD in at least two transport compartments, separable by their sensitivity to CCCP. The inhibition of the secretory pathway at both steps is reversible; upon removal of the drug the arrested IgD is processed normally and is secreted. The sensitivity to CCCP probably reflects transport steps that are sensitive to even partial depletion of ATP, because treatments with other inhibitors of oxidative phosphorylation yield similarly arrested Ig molecules. Thus, by using the protonophore CCCP, we demonstrate two energy-requiring steps in IgD transport which seem to be at two transitions in the secretory pathway. One step is during the passage from the endoplasmic reticulum to the mid-Golgi compartment and the other step is during Ig passage through the trans-Golgi, or subsequent transport to the cell surface. PMID- 2911011 TI - The murine complement receptor gene family. Analysis of mCRY gene products and their homology to human CR1. AB - The mouse genome contains two sets of gene sequences which are highly homologous to the gene encoding the human C3b/C4b receptor (CR1). These genes, termed murine CRY (mCRY) and murine CRX (mCRX) reside on murine chromosomes 1 and 8, respectively. Analysis of cDNA isolated by using these sequences as probes indicates that there are two related but distinct mRNA which are expressed in a wide variety of murine tissues including spleen, liver, lung, and brain. Both of these transcripts encode proteins which should contain a signal sequence for membrane insertion, a transmembrane/cytoplasmic tail region for membrane anchoring, and five extracellular domains made up of 60 amino acid consensus repeat sequences. The difference between the two is the presence of an additional exon of 129 bp immediately 3' of the signal sequence. This additional exon does not encode a 60 amino acid repeat. The sizes of the mature proteins predicted from the cDNA sequences are 43,998 Mr and 48,680 Mr; however, antisera raised against carboxy-terminal sequences detects a 70,000 Mr protein from murine fibroblasts suggesting a high degree of post-translational modification of the mature protein. A comparison of these murine gene sequences with a partial human CR1 sequence suggests that the human CR1 gene evolved by direct duplication of the ancestral coding sequences contained within these murine genes including those sequences important for membrane anchoring and cytoplasmic protein attachment. PMID- 2911012 TI - Recurrent somatic mutations in mouse antibodies to p-azophenylarsonate increase affinity for hapten. AB - Two mouse mAb specific for the hapten p-azophenylarsonate and encoded by the same combination of germ-line V, D, and J genes differ 200-fold in affinity for hapten. We determined the amino acid sequences of the V regions of the high affinity antibody and compared them to the published sequences of the low affinity antibody which is not somatically mutated. Of 19 amino acid substitutions, two, Ile57 and Thr58 in the H chain, also occur, either alone or together, in other somatically mutated antibodies specific for p azophenylarsonate; these antibodies have been independently isolated. Introduction of either one of these mutations alone into the low affinity antibody by oligonucleotide-directed mutagenesis increased the antibody affinity for hapten three- to fourfold, whereas introduction of both mutations together conferred an eightfold increase in affinity. These results support the hypothesis that somatic mutations are selected on the basis of the affinity for antigen that they confer, and suggest that even relatively small increases in affinity may be selected, probably in a sequential manner. PMID- 2911013 TI - Identification of carboxypeptidase and tryptic esterase activities that are complexed to proteoglycans in the secretory granules of human cloned natural killer cells. AB - Human cloned 35S-labeled NK cells were disrupted by nitrogen cavitation, and their secretory granules were obtained by filtration through 5-micron and 3 micron membrane filters followed by Percoll density-gradient centrifugation. These granule preparations, which contained 35S-labeled chondroitin sulfate A proteoglycans, were sonicated and were analyzed for carboxypeptidase activity and tryptic serine esterase activity. A carboxypeptidase activity that digested angiotensin I to des-Leu-angiotensin I, Ile-His-Pro-Phe to Ile-His-Pro and Phe, and hippuryl-L-phenylalanine to hippuric acid and Phe was detected in the granules of these NK cells. As determined by cleavage of the tetrapeptide, the pH optimum of the carboxypeptidase was 7.0. As assessed by the cleavage of N benzyloxycarbonyl-L-lysine thiobenzyl ester (BLTe), the granule preparations also contained a serine esterase with trypsin-like specificity that had a pH optimum of 8.5. When the isolated secretory granules were disrupted and chromatographed on columns of Sepharose CL-2B in PBS, greater than 60% of the BLTe serine esterase activity and essentially all of the carboxypeptidase activity filtered as a macromolecular complex with approximately 8% of the 35S-labeled proteoglycans. Whereas treatment with 4 M urea or nonionic detergent failed to disrupt the macromolecular complex, the serine esterase activity was dissociated from the macromolecular complex in the presence of 3 M NaCl, demonstrating an ionic interaction with the proteoglycans. No difference was observed in the disaccharide composition of the chondroitin sulfate glycosaminoglycans of the 35S labeled proteoglycans that were complexed with the enzymes as compared to those that were not complexed. These studies indicate that the secretory granules of human NK cells contain serine esterase activity and carboxypeptidase activity, both of which have neutral pH optima, and both of which are bound to protease resistant chondroitin sulfate proteoglycans. PMID- 2911014 TI - Dual mechanisms in priming of the chemoattractant-induced respiratory burst in human granulocytes. A Ca2+-dependent and a Ca2+-independent route. AB - After interaction with so-called priming agents, the respiratory burst in human granulocytes does not become activated, but is enhanced upon subsequent stimulation with the chemoattractant FMLP. Investigating the mechanism of the priming reaction, we found that a transient rise in the cytosolic free calcium concentration [( Ca2+]i) suffices to irreversibly prime human granulocytes. Thus, platelet-activating factor (PAF) induced a transient increase in [Ca2+]i and primed the cells to an enhanced respiratory burst upon subsequent interaction with FMLP. Artificially, the transient rise in [Ca2+]i was mimicked by addition and subsequent removal of the Ca2+ ionophore ionomycin; this treatment too, primed the respiratory burst of the granulocytes. The priming induced by ionomycin was completely abolished when [Ca2+]i changes were buffered during exposure of the cells to the ionophore. The priming induced by PAF was only partially inhibited under [Ca2+]i-buffering conditions during priming, indicating that multiple pathways exist in the priming of granulocytes by PAF. PMID- 2911015 TI - Structural requirements for IgM assembly and cytolytic activity. Effects of mutations in the oligosaccharide acceptor site at Asn402. AB - Glycosylation of IgG occurs at asparagine 297 of the gamma H chain and is necessary for the normal capacity of IgG to activate the classical pathway of complement-dependent cytolysis. IgM is glycosylated at five sites in the constant region of the mu H chain, of which glycosylation at asparagine 402 seems analogous to the glycosylation of IgG. In order to assess the importance of glycosylation at asparagine 402 for IgM cytolytic activity, we have used site directed mutagenesis to produce IgM which is not glycosylated at this position. In particular we have tested the effects of substituting Gln for Asn 402 and Thr Gly for Gly 403-Thr 404 in the third constant region domain. We tested the effects of these substitutions by expressing the mutant mu genes in hybridoma cells which produce the hapten-specific kappa-chain. The normal mu-chain is glycosylated at Asn 402, and, as expected, these mutations appear to abrogate glycosylation of the mutant mu-chains at position 402 and do not affect the hapten affinity of the IgM. However, both of these mutations cause the increased production of monomeric rather than polymeric IgM: the ratio of monomeric to polymeric IgM is 0.21, 3.5, and 10.3 for wild-type IgM, IgM-Gln 402, and IgM-Thr 403-Gly 404, respectively. The wild-type and mutant polymeric IgM preparations were compared for their capacity to promote complement-dependent cytolysis: IgM Gln 402 and IgM-Thr 403-Gly 404 have approximately 31% and 4%, respectively, of the capacity of wild-type IgM. PMID- 2911016 TI - Binding of monomeric and aggregated immunoglobulin to enzymes. A source of artefact in antibody assays. AB - Pepsinogen has previously been shown to bind non-specifically to immune complexes and aggregated immunoglobulins. We demonstrate here using a solid-phase immunoassay that immunoglobulins aggregated by heat or glutaraldehyde bind non specifically to several different enzymes. Some of these, including pepsinogen (marketed as pepsin), hyaluronidase and trypsin, are used in the breakdown of tissues or biochemical preparations during the preparation of antigens. Contamination of impure antigens by enzyme is likely to lead to products which bind non-specifically to immune complexes. This can cause misidentification of complexes as antibodies. We recommend that all tests for specific antibody involving the use of antigens prepared by these or other enzymes should include a control with aggregated immunoglobulin substituted for the test serum. PMID- 2911017 TI - Specific and sensitive detection of purified HLA molecules in an ELISA using mouse, rabbit and human anti-HLA antibodies. AB - An ELISA detecting anti-HLA antibodies of rabbit, mouse or human origin was developed using plates coated with HLA molecules purified on affinity columns. The sensitivity of the assay was optimal when coating was performed in PBS, pH 7.8 at 4 degrees C for 6-16 h and using a serum incubation period of 16 h at 4 degrees C. The optimum protein concentration for coating was estimated to be 1 micrograms/ml. With monoclonal anti-HLA sera, antipeptide antibodies from mice or rabbit and human alloantisera, this method appeared to be highly sensitive, very specific and reproducible. PMID- 2911018 TI - A single step centrifugation method for the enrichment of veiled cells from canine afferent lymph. AB - Veiled cells (VC) present in the afferent lymph of dogs with chronic lymphoedema could be enriched from 6% to about 50% VC by density gradient centrifugation on 15% metrizamide or discontinuous Percoll gradients. The recovery of VC was about 40% from 0.22 +/- 0.07 X 10(6) VC/ml of lymph. The cells were strongly Ia positive and had cytoplasmic S 100 protein. They were also strongly ATP-ase positive and showed heterogeneity in acid phosphatase, peroxidase and non specific esterase activity. Low density VC from canine afferent lymph were able to stimulate both blood and lymphatic lymphocytes in autologous mixed leukocyte reaction when present at concentration as low as 5% of cultured cells. PMID- 2911019 TI - Effect of fibronectin on antigen-induced lymphoproliferation and antibody synthesis in rats. AB - Macrophages are important positive and negative regulators of both primary and secondary antibody responses, and their activity may, in turn, be controlled by soluble mediators secreted by other cells. Fibronectin is a 440,000 dalton normal constituent of plasma and extracellular membranes that acts through macrophages to inhibit mitogen- and alloantigen-stimulated lymphoproliferation. We examined the effect of Fn on the antigen-stimulated lymphoproliferative and antibody responses in cells from trinitrophenol-derivitized keyhole limpet hemocyanin (TNP KHL) primed rats. Fn in concentrations equivalent to normal plasma levels inhibited TNP-KLH-stimulated lymphoproliferation by unseparated lymph node leukocytes. When the experiment was repeated using purified lymph node T cells and added thioglycollate-induced peritoneal exudate macrophages or splenic adherent macrophages, Fn alone and TNP-KLH alone stimulated lymphoproliferation, but in combination they were strongly inhibitory. The effect was not due to decreased lymphocyte viability in the presence of both TNP-KLH and Fn. Nor was it due to complexes between TNP-KLH and Fn or to a simple alteration in the kinetics of lymphoproliferation. Fn had to be present with the TNP-KLH within the 1st hour of incubation. If macrophages were coincubated with TNP-KLH and Fn for 24 h, washed, and added to enriched T cells, inhibition was equivalent to that seen with continuous coculture. Similarly, coculture of TNP-KLH and Fn inhibited both total immunoglobulin and TNP-KLH-specific antibody synthesis at optimal concentrations of splenic adherent cells. However, at suboptimal levels of splenic macrophages, the combination was synergistic, stimulating more total immunoglobulin synthesis than either TNP-KLH or Fn alone. These data suggest that the inhibitory effect was dependent upon the concentration and phenotype of macrophages present in culture. PMID- 2911020 TI - Biosynthesis of proteochondroitin sulfate by HL-60 human promyelocytic cells. AB - Human promyelocytic cells (HL-60) were labeled with 35S-sulfate and either 3H glucosamine or 3H-serine as precursors. Accumulation of 35S-labeled macromolecules was approximately linear for up to 96 h, with a mean cell:medium ratio of 5.5:1, although activity/10(5) viable cells reached a plateau level after 24 h. Virtually none of the cell-associated proteoglycan was removed by trypsinization, consistent with a predominantly intracellular localization. Proteoglycan heterogeneity was investigated by DEAE-Sephacel chromatography, isopyknic CsCl gradient centrifugation, and gel filtration chromatography. HL-60 cells appeared to synthesize a single proteoglycan species, Kav = 0.46 on Sepharose CL-4B and Kav = 0.32 on Sepharose CL-6B, recovered primarily from the high-density fractions of a dissociative CsCl gradient (rho greater than 1.40 g/l). Degradation products of lower charge density, lower buoyant density, and lower hydrodynamic size were also present, mainly in the cell pellets. The major proteoglycan was found to contain chondroitin sulfate chains of average Mr = 14.5 kD, yielding virtually 100% 4-sulfated disaccharides on digestion with chondroitinase ABC. The proteoglycan was resistant to trypsin, chymotrypsin, plasmin, and papain, and the core protein Mr was approximately 20 kD by molecular sieve chromatography. Induction of HL-60 cells with 0.15 dimethyl sulfoxide (DMSO) resulted in differentiation to a more mature granulocytic phenotype and was associated with a reduction in 35S-sulfate incorporation to 45% of control values or 32%, expressed as activity/10(5) cells. Proteoglycans synthesized by DMSO-treated cells were identical to those from untreated cells in terms of hydrodynamic size, glycosaminoglycan Mr, and sulfation. PMID- 2911021 TI - Polyclonal anti-idiotypes influence macrophage chemotaxis in coxsackievirus induced murine myocarditis. AB - Investigation into the mechanism(s) whereby monocytes-macrophages are mobilized to the myocardium of coxsackievirus (CVB3)-infected mice was approached by assessing the role of anti-idiotypic antibodies against specific antiviral IgG molecules. Balb/c mice preinoculated with polyclonal anti-idiotypic, syngeneic antibodies resulted in significantly decreased myocarditis after virus challenge. On the other hand, oil-induced peritoneal exudate cells obtained from virus exposed animals demonstrated increased chemotaxis in the presence of polyclonal anti-Id preparations, whereas peritoneal exudate cells from normal animals did not. Specificity of the anti-Ids as confirmed by the binding of the syngeneic anti-anti-idiotypic antibodies (antibody 3) to solubilized viral antigen(s) and Fab fragments prepared from the anti-idiotypic antibodies. Paradoxic biological effects of anti-Id, demonstrated in vitro and in vivo, suggest possible and subtle immunoregulation of the macrophage effector arm by anti-idiotypes during the course of virus infection. PMID- 2911022 TI - Source of methyl groups in brain and nerve tissue in the rat. AB - Previous studies that demonstrated that mouse brain accumulated significantly more radioactivity from subcutaneously administered 5-methyltetrahydrofolate labelled in the methyl group compared to the label in the folate moiety are open to two interpretations. The methyl group could have been transferred to another compound (probably methionine) prior to its transport into the brain. Alternatively, if plasma 5-methyltetrahydrofolate per se is significantly involved in the provision of methyl groups to brain and nerve tissue it would be expected that the folate moiety would be returned to the plasma to complete the cycle and thus would appear not to have been taken up. In this article, using competition experiments that exploit the differences in the mechanism of transport of methionine and 5-methyltetrahydrofolate into brain and nerve, evidence is presented that in the rat the methyl group of 5 methyltetrahydrofolate is transported after its conversion to methionine. PMID- 2911023 TI - Basal lipid peroxidation in substantia nigra is increased in Parkinson's disease. AB - Polyunsaturated fatty acid (PUFA) levels (an index of the amount of substrate available for lipid peroxidation) were measured in several brain regions from patients who died with Parkinson's disease and age-matched control human postmortem brains. PUFA levels were reduced in parkinsonian substantia nigra compared to other brain regions and to control tissue. However, basal malondialdehyde (MDA; an intermediate in the lipid peroxidation process) levels were increased in parkinsonian nigra compared with other parkinsonian brain regions and control tissue. Expressing basal MDA levels in terms of PUFA content, the difference between parkinsonian and control substantia nigra was even more pronounced. Stimulating MDA production by incubating tissue with FeSO4 plus ascorbic acid, FeSO4 plus H2O2, or air alone produced lower MDA levels in the parkinsonian substantia nigra, probably reflecting the lower PUFA content. These results may indicate that an increased level of lipid peroxidation continues to occur in the parkinsonian nigra up to the time of death, perhaps because of continued exposure to excess free radicals derived from some endogenous or exogenous neurotoxic species. PMID- 2911024 TI - Distribution of activity converting 4-aminobutyraldehyde to gamma-aminobutyric acid in subcellular fractions of mouse brain. AB - The subcellular distribution of activity of 4-aminobutyraldehyde dehydrogenase (ABAL-DH) was studied in mouse brain. ABAL-DH was localized mainly in the crude mitochondrial fraction; most of the activity in this fraction was found in the subfraction containing synaptosomes, and the remainder was in the mitochondrial fraction. After osmotic disruption of synaptosomes, most of the activity was located in the synaptic cytosol, and the remainder was in the synaptic mitochondria. Sucrose density subfractionation of synaptosomes revealed that gamma-aminobutyric acid, glutamic acid decarboxylase, and ABAL-DH localized in a denser region of gradient fraction than the region containing acetylcholinesterase and choline acetyltransferase. PMID- 2911025 TI - Diurnal variation in the function of serotonin terminals in the rat hypothalamus. AB - The high-affinity binding of [3H]imipramine is associated with the serotonin (5 hydroxytryptamine; 5-HT) transporter in the brain and in platelets. In the rat hypothalamus it has been reported that the density of these sites is increased in the dark period of the day, and this could result in an alteration in the release of 5-HT. The electrically evoked release of [3H]5-HT was thus studied in preloaded hypothalamic slices prepared from rats kept under 12:12 h light/dark or dark/light schedules. The fractional release of [3H]5-HT evoked by electrical stimulation, but not by the 5-HT releasing agent fenfluramine, was significantly decreased during the dark period when compared with the light period. The effects of the 5-HT reuptake blocker citalopram, of the two 5-HT autoreceptor agonists 5 methoxytryptamine and RU 24969, and of the 5-HT autoreceptor antagonist methiothepin on the release of [3H]5-HT were the same in both groups of rats. In conclusion, the release of [3H]5-HT from prelabelled rat hypothalamic slices is decreased during the dark period of the day. This modification is not reflected by changes in the effects of citalopram, an inhibitor of 5-HT reuptake, to modify the overflow of [3H]5-HT. The sensitivity and efficacy of agonists of the 5-HT autoreceptor are the same during the light and dark periods of the day. PMID- 2911026 TI - Ganglioside composition of normal and mutant mouse embryos. AB - The enrichment of gangliosides in neuronal membranes suggests that they play an important role in CNS development. We recently found a marked tetrasialoganglioside deficiency in twl/twl mutant mouse embryos at embryonic day (E)-11. The recessive twl/twl mutants die at embryonic ages E-9 to E-18 from failed neural differentiation in the ventral portion of the neural tube. In the present study, we examined the composition and distribution of gangliosides in twl/twl mutant mouse embryos at E-12. The total ganglioside sialic acid concentration was significantly lower in the mutants than in normal (+/-) embryos. The mutants also expressed significant deficiencies of gangliosides in the "b" metabolic pathway (GD3, GD1b, GT1b, and GQ1b) and elevations in levels of gangliosides in the "a" metabolic pathway (GM3, GM2, GM1, and GD1a). These findings suggest that the mutants have a partial deficiency in the activity of a specific sialyltransferase in the b pathway. Regional ganglioside distribution was also studied in E-12 normal mouse embryos. The ganglioside composition in heads and bodies was similar to each other and to whole embryos. Total ganglioside concentration and the distribution of b pathway gangliosides were significantly higher in neural tube regions than in nonneural tube regions. These findings suggest that b pathway gangliosides accumulate in differentiating neural cells and that the deficiency of these gangliosides in the twl/twl mutants is closely associated with failed neural differentiation. PMID- 2911027 TI - Effect of chronic nicotine treatment on nicotinic autoreceptor function and N [3H]methylcarbamylcholine binding sites in the rat brain. AB - It has been reported that N-methylcarbamylcholine (MCC), a nicotinic agonist, binds to central nicotinic receptors and causes an increase of acetylcholine (ACh) release from certain central cholinergic nerve terminals. The present experiments determine whether these two phenomena change in response to the chronic administration of nicotine, a procedure known to result in an increase in nicotinic binding sites. Chronic nicotine caused a brain region-specific up regulation of [3H]MCC sites; binding increased in the frontal cortex, parietal cortex, striatum, and hippocampus, but not in the occipital cortex or cerebellum. The effect of nicotine was selective to nicotinic binding sites, because muscarinic sites, both M1 ([ 3H]pirenzepine) and M2 ([3H]ACh), were unaffected by chronic nicotine treatment. MCC increased the release of ACh from the frontal cortex and hippocampus by a calcium-dependent mechanism; MCC did not alter ACh release from striatum or occipital cortex of control animals. The MCC-induced increase in ACh release was not apparent in those animals which had been treated with nicotine. There was a partial recovery of nicotinic autoreceptor function when animals were allowed to recover (4 days) following chronic nicotine treatment, but the density of binding sites remained increased compared to control. Chronic nicotine did not change the potassium-evoked release of ACh from the frontal cortex or hippocampus, but decreased this measure from striatum. It also decreased the ACh content of the striatum, but not that of the cortex or the hippocampus; the activity of choline acetyltransferase was not altered in any of the regions tested.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2911029 TI - Highly basic 30- and 32-kilodalton proteins associated with synapse formation on polylysine-coated beads in enriched neuronal cell cultures. AB - Neuronal proteins involved in axonal outgrowth and synapse formation were examined in an enriched neuronal cell culture system of the cerebellum. In rat cerebellar cell cultures, 98.9% of the cells are neurons and the remaining 1.1% of the cells are flat nonneuronal cells. These enriched neuronal cultures, examined with two-dimensional gel electrophoresis, showed protein patterns similar to those of neonatal cerebellum, but very different patterns from glial enriched cultures. High levels of a neuronal membrane acidic 29-kilodalton (kD) protein were found. It has been shown previously that neuronal cultures incubated with polylysine-coated beads will develop numerous presynaptic elements on the bead surface. We report here that isolation of the beads from enriched neuronal cell cultures incubated with [35S]methionine showed, with two-dimensional nonequilibrium pH gradient gel electrophoresis (2D-NEPHGE), levels of a basic 32 kD protein (pI 8) note detected in cultures alone, and increased levels of a 30 kD protein (pI 10). When culture medium was examined with 2D-NEPHGE, three acidic proteins were identified that were secreted by the cultured neurons. In summary, a neuronal enriched cell culture system was used with isolated polylysine-coated beads to identify basic 30-kD and 32-kD proteins that may be involved in synapse formation. PMID- 2911028 TI - Transition metals, ferritin, glutathione, and ascorbic acid in parkinsonian brains. AB - The regional distributions of iron, copper, zinc, magnesium, and calcium in parkinsonian brains were compared with those of matched controls. In mild Parkinson's disease (PD), there were no significant differences in the content of total iron between the two groups, whereas there was a significant increase in total iron and iron (III) in substantia nigra of severely affected patients. Although marked regional distributions of iron, magnesium, and calcium were present, there were no changes in magnesium, calcium, and copper in various brain areas of PD. The most notable finding was a shift in the iron (II)/iron (III) ratio in favor of iron (III) in substantia nigra and a significant increase in the iron (III)-binding, protein, ferritin. A significantly lower glutathione content was present in pooled samples of putamen, globus pallidus, substantia nigra, nucleus basalis of Meynert, amygdaloid nucleus, and frontal cortex of PD brains with severe damage to substantia nigra, whereas no significant changes were observed in clinicopathologically mild forms of PD. In all these regions, except the amygdaloid nucleus, ascorbic acid was not decreased. Reduced glutathione and the shift of the iron (II)/iron (III) ratio in favor of iron (III) suggest that these changes might contribute to pathophysiological processes underlying PD. PMID- 2911030 TI - pros-methylimidazoleacetic acid in rat brain: its regional distribution and relationship to metabolic pathways of histamine. AB - pros-Methylimidazoleacetic acid (p-MIAA; 1-methylimidazole-5-acetic acid), an isomer of the histamine metabolite, tele-methylimidazoleacetic acid (t-MIAA), is present in brain and CSF. Its relationship to histamine synthesis and catabolism was assessed in brains of rats. p-MIAA distribution in brain regions was heterogeneous although the concentrations in regions with the highest (hypothalamus) and the lowest (medulla-pons) levels differed less than four-fold. There was no significant correlation between the regional distributions of p-MIAA with those of histamine or its metabolites. pros-Methylhistidine (1 g/kg, i.p.) produced a 20-fold increase in mean levels of p-MIAA and up to a 50-fold increase in levels of pros-methylhistamine (p-MH), a putative intermediate; levels of histamine and its metabolites were unaltered. L-Histidine (1 g/kg, i.p.) or alpha fluoromethylhistidine (100 mg/kg, i.p.), the irreversible inhibitor of histamine synthesis, did not alter the levels of p-MIAA in brain. Like the levels of t MIAA, the levels of p-MIAA were unaltered after probenecid administration. Contrary to its effects in lowering t-MIAA levels, pargyline (75 mg/kg, i.p.) produced a slight rise in levels of p-MIAA in all regions. These findings suggest that, in brain, the metabolic pathways of histamine are independent of pathways that generate p-MIAA. Further, since brain is capable of p-MH formation, its use as an internal standard in analytical methods merits caution. PMID- 2911031 TI - Effects of vitamin A and its analogs on nonenzymatic lipid peroxidation in rat brain mitochondria. AB - Vitamin A (retinol) and some of its analogs exhibited varying degrees of inhibition on induced iron and ascorbic acid lipid peroxidation of rat brain mitochondria. Malonyldialdehyde production was used as an index of the extent of in vitro lipid peroxidation. The fat-soluble vitamins retinol, retinol acetate, retinoic acid, retinol palmitate, and retinal at concentrations between 0.1 and 10.0 mmol/L inhibited brain lipid peroxidation. Retinol and retinol acetate were the most effective inhibitors. It is concluded from this study that retinol and its analogs can be considered as potential antioxidant factors, more potent than some of the well-known antioxidants such as alpha-tocopherol and butylated hydroxytoluene. PMID- 2911032 TI - Effects of hypoglycaemia and hypoxia on the intracellular pH of cerebral tissue as measured by 31P nuclear magnetic resonance. AB - Changes in high-energy phosphate metabolites and the intracellular pH (pHi) were monitored in cerebral tissue during periods of hypoglycaemia and hypoxia using 31P nuclear magnetic resonance spectroscopy. Superfused brain slices were loaded with deoxyglucose at a concentration shown not to impair cerebral metabolism, and the chemical shift of the resulting 2-deoxyglucose-6-phosphate (DOG6P) peak was used to monitor the pHi. In some experiments with low circulating levels of Pi, the intracellular Pi was visible and indicated a pH identical to that of DOG6P, an observation validating its use as an indicator of pHi in cerebral tissue. The pHi was found to be unchanged during moderate hypoglycaemia; however, mild hypoxia (PO2 = 16.4 kPa) and severe hypoglycaemia produced marked reductions from the normal of 7.2 to 6.8 and 7.0, respectively. Hypoglycaemia caused a fall in the level of both phosphocreatine (PCr) and ATP, whereas hypoxia affected PCr alone, as shown previously. However, the fall in pHi was similar during the two insults, thus indicating that the change in pH is not directly linked to lactate production or to the creatine kinase reaction. PMID- 2911033 TI - Choline acetyltransferase activities in single spinal motor neurons from patients with amyotrophic lateral sclerosis. AB - Activities of choline acetyltransferase (ChAT) were microassayed in individual cell bodies of motor neurons, isolated from freeze-dried sections after autopsy of lumbar spinal cords from four patients with sporadic amyotrophic lateral sclerosis (ALS) and four control patients with nonneurological diseases. Numerous large neurons were found in the anterior horn at the early degeneration stage of ALS, but the cell bodies atrophied and decreased in number at the late advanced stage. The small, atrophied neurons were very fragile and were easily destroyed during the isolation procedure with a microknife. The average activity, expressed on a dry weight basis, of 58 ALS neurons was lower than that of 67 control neurons. The large, well-preserved neurons at the early nonadvanced stage had markedly lower ChAT activities than control neurons. The specific activity gradually increased with the progress of atrophy but did not return to the control level. PMID- 2911034 TI - Electroconvulsive shock (ECS) and the adenosine neuromodulatory system: effect of single and repeated ECS on the adenosine A1 and A2 receptors, adenylate cyclase, and the adenosine uptake site. AB - The effect of a single electroconvulsive shock (ECS) (30 min and 24 h after treatment) and repeated ECS (10 once-daily) on the adenosine neuromodulatory system was investigated in rat cerebral cortex, cerebellum, hippocampus, and striatum. The present study examined the adenosine A1 receptor using N6 [3H]cyclohexyladenosine ([3H]CHA), the A2 receptor using 5'-N [3H]ethylcarboxyamidoadenosine ([ 3H]NECA), adenylate cyclase using [3H]forskolin, and the adenosine uptake site using [3H]nitrobenzylthioinosine ([3H]NBI). At 30 min after a single ECS, the Bmax of the [3H]NBI binding in striatum was increased by 20%, which is in good agreement with the well-known postictal adenosine release. The Bmax of [3H]forskolin binding in striatum and cerebellum was increased by 60 and 20%, respectively. In contrast to earlier reported changes following chemically induced seizures, [3H]CHA binding was not altered postictally. At 24 h after a single ECS, there were no changes for any ligand in any brain region. Following repeated ECS, there was a 20% increase of [3H]CHA binding sites in cerebral cortex, which lasted for at least 14 days after the last ECS. [3H]Forskolin binding in hippocampus and striatum was 20% lowered 24 h after 10 once-daily ECS but had already returned to control levels 48 h after the last treatment. Evidence is provided that the upregulated adenosine A1 receptors are coupled to guanine nucleotide binding proteins and, furthermore, that this upregulation is not paralleled by an increase in adenylate cyclase activity as labeled by [3H]forskolin. PMID- 2911035 TI - Oxidation of N-methyl-1,2,3,4-tetrahydroisoquinoline into the N-methyl isoquinolinium ion by monoamine oxidase. AB - N-Methyl-1,2,3,4-tetrahydroisoquinoline (NMTIQ) was found to be oxidized by monoamine oxidase (MAO) into N-methylisoquinolinium ion, which was proved to inhibit enzymes related to the metabolism of catecholamines, such as tyrosine hydroxylase, aromatic-L-amino acid decarboxylase, and MAO. NMTIQ was oxidized by both types A and B MAO in human brain synaptosomal mitochondria. Oxidation was dependent on the amount of MAO sample and the reaction time. Enzyme activity with respect to NMTIQ reached optimum at a pH of approximately 7.25, as was the case with other substrates. Type A MAO had higher activity for this substrate than type B. The Km and Vmax values of the oxidation by types A and B MAO were 571 +/- 25 microM and 0.29 +/- 0.06 pmol/min/mg protein, and 463 +/- 43 microM and 0.16 +/- 0.03 pmol/min/mg protein, respectively. The Vmax values of types A and B MAO for NMTIQ were much smaller than those for other substrates such as kynuramine. NMTIQ was the first tetrahydroisoquinoline shown to be oxidized into the isoquinolinium ion by MAO in the brain. PMID- 2911036 TI - Evidence for distinct 5-hydroxytryptamine2 binding site subtypes in cortical membrane preparations. AB - 5-Hydroxytryptamine (5-HT) displays a sixfold higher affinity for 5-HT2 binding sites labeled by [3H]ketanserin in rat (IC50 = 200 +/- 40 nM) and human (IC50 = 190 +/- 50 nM) cortex than for 5-HT2 sites in bovine cortex (IC50 = 1,200 +/- 130 nM). The Hill slopes of the 5-HT competition curves are 0.67 +/- 0.04 in rat, 0.69 +/- 0.08 in human, and 0.96 +/- 0.02 in bovine cortex. Scatchard analysis of (+/-)-[3H]4-bromo-2,5-dimethoxyamphetamine ([3H]DOB) binding in the rat indicates a population of binding sites with a KD of 0.38 +/- 0.04 nM and a Bmax of 1.5 +/- 0.05 pmol/g tissue. In contrast, specific [3H]DOB binding cannot be detected in bovine cortical membranes. These data indicate that species variations exist in 5 HT2 binding site subtypes and that [3H]ketanserin appears to label a homogeneous population of 5-HT2 binding site subtypes in bovine cortex. PMID- 2911037 TI - Assessment of the purity of d,l HM-PAO from diastereomeric mixtures using NMR techniques. AB - We have shown that 1H NMR can serve as a suitable analytical tool for the assessment of relative amounts of d,l and meso HM-PAO isomers in a diastereomeric mixture and for the determination of the purity of either one of the two diastereomers alone. Therefore, we believe that this method will be useful for quality control in both academic and government regulatory laboratories as well as for radiopharmaceutical manufacturers. In addition, this analytical tool can provide rapid screening of possible suitable stereospecific reducing agents for the preferential formation of the d,l HM-PAO diastereomer without the necessity of completely working up the reduction reaction mixture. PMID- 2911038 TI - Discrepant sulfur colloid and radioparticle liver uptake in superior vena cava obstruction: case report. AB - The presence of collateral venous channels connecting the upper extremity veins and portal vein via the paraumbilical veins is considered the probable explanation for the observed scintigraphic hepatic "hot spot". This is seen in [99mTc]sulfur colloid liver imaging and perfusion lung imaging with 99mTc radiolabeled particles injected into an antecubital vein in the presence of superior vena caval (SVC) obstruction. The typical distribution is one of focal uptake centrally, anteriorly, and inferiorly. An unusual pattern is described in this report and mechanisms proposed for the "diffuse homogeneous" hepatic uptake also observed in a patient with SVC obstruction undergoing a perfusion lung scan. PMID- 2911039 TI - The use of radionuclide cisternography in the diagnosis of pleural cerebrospinal fluid fistulae. AB - Radionuclide cisternography (RNC) is an excellent method of studying cerebrospinal fluid (CSF) dynamics and fistulous communications. Two patients are described in which pleural cerebrospinal fluid fistulae were found by this technique. In addition, marking the area presurgically reduced operating room time in one patient. Such communications are important to locate since they can cause significant loss of CSF as well as provide a pathway for pathogens to enter the central nervous system. PMID- 2911040 TI - Excretion of radioiodine in breast milk. PMID- 2911041 TI - Excretion of radioiodine in breast milk. PMID- 2911042 TI - Forearm blood flow measurements using technetium-99m human serum albumin following brachial arteriotomy. AB - A simple, low cost method for measuring forearm blood flow during reactive hyperemia has been developed. Subjects are seated with hands and forearms over a large field-of-view gamma camera. Blood pressure cuffs inflated above the elbows isolate the blood in the forearms and hands and induce a hyperemic response. The remaining blood pool is labeled with technetium. The rate of increase of activity following release of the cuffs is measured from the gradient of time-activity curves and is calibrated for flow by counting a venous blood sample. The technique has been applied to a group of normal controls and to symptomatic and asymptomatic patients following right brachial arteriotomy. Forearm blood flow in normal subjects was 32.9 +/- 6.4 ml/100 ml/min and for subjects with occlusion of the brachial artery was 6.4 +/- 2.1 ml/100 ml/min. The method is simple, widely available, and reproducible. The good signal to noise ratio allows it to be used in cases of very low flow either as an aid to diagnosis or to measure treatment response. PMID- 2911043 TI - Improved radiolabeled monoclonal antibody uptake by lavage of intraperitoneal carcinomatosis in mice. AB - The effect of peritoneal lavage with saline on tumor and systemic uptake of intraperitoneally administered tumor-specific (131I-5G6.4) and nonspecific (125I UPC-10) radiolabeled monoclonal antibodies was evaluated in a nude mouse model of human intraperitoneal ovarian carcinomatosis (IP3 model). Peritoneal lavage at 2 or 6 hr postintraperitoneal antibody injection significantly improves intraperitoneal tumor/nontumor uptake ratios of specific antibody apparently by limiting systemic exposure to antibody. This enhancement tends to be more dramatic if lavage is performed within 2 hr, rather than 6 hr, of intraperitoneal antibody administration, though both times result in significant improvements in target/background ratios over no lavage. Twenty-four-hour tumor/nontumor ratios for specific antibody 5G6.4 generally are 1.5-fourfold higher following lavage than those achieved in control animals, without decreasing absolute tumor uptake of specific radiolabeled antibody. By contrast, nonspecific antibody UPC-10 binding is lower in tumor and normal tissues following lavage, with no lavage induced improvement in tumor/nontumor ratios seen. Peritoneal lavage is a simple method to allow for specific antibody binding to accessible intraperitoneal tumors yet to limit systemic exposure thus increasing the therapeutic margin. This method may have considerable applicability in the enhancement of intraperitoneal immunoconjugate delivery to intraperitoneal tumors. PMID- 2911044 TI - Rapid blood clearance of biotinylated IgG after infusion of avidin. AB - The techniques of immunotherapy and radioimmunoimaging suffer from the problem of background: intravenously injected antibodies remain in the circulation much longer than it is necessary for effective binding to the target. Various approaches, including the postinjection of second antibodies, were explored to overcome the problem with some success. The phenomenon of a 100-fold more rapid blood clearance of biotinylated immunoglobulins after postinjection of an equivalent dose of avidin is described. The concentration of 125I-labeled biotinylated IgG in the circulation of rats slowly decreased to 20% of initial in 24 hr. Avidin injection at any interval during this period induced 90-95% reduction of radioactivity in blood in 15 min. Up to 70% of the radioactivity was recovered in the liver. Avidin-induced blood clearance of biotinylated immunoglobulins may find applications in immunotherapy and radio- or nuclear magnetic resonance immunoimaging. PMID- 2911045 TI - Dual tracer autoradiographic study with thallium-201 and radioiodinated fatty acid in cardiomyopathic hamsters. AB - To investigate the usefulness of myocardial scintigraphy with radioiodinated 15 (p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) in cardiomyopathy, quantitative dual tracer autoradiographic study with 201Tl and [125I]BMIPP was performed in 27 cardiomyopathic Bio 14.6 Syrian hamsters and eight normal hamsters. Furthermore, 16 Bio 14.6 Syrian hamsters aged 21 days were divided into verapamil-treated (during 70 days) and control groups (respectively, n = 8), and autoradiography with 201Tl and [125I]BMIPP was performed. Quantitative autoradiography demonstrated an uncoupling of 201Tl and [125I]BMIPP distributions and a regional heterogeneity of [125I]BMIPP distribution in cardiomyopathic hamsters aged more than 2 mo, while normal hamsters showed only mild heterogeneity of [125I]BMIPP distribution without an uncoupling of tracers. Age matched comparison between normal and cardiomyopathic hamsters (5-8 mo old) demonstrated that a difference between their [125I]BMIPP distributions are more marked than that between their 201Tl distributions. Furthermore, [125I]BMIPP visualized effects of verapamil on cardiomyopathy more distinctly than did 201Tl. In conclusion, myocardial imaging with [123I]BMIPP could be useful for investigating cardiomyopathy and evaluating the efficacy of therapeutic intervention in patients with cardiomyopathy. PMID- 2911046 TI - CNO and CEO decision-making patterns and compatability: Part 2, Using the MBTI. PMID- 2911047 TI - Preventing drug dependency: Part 2, Educating and supporting staff. AB - Nurse administrators can respond to the chemical abuse problem in one of two ways. They can deny it, ignore it, avoid confrontation, and terminate the employee. Such action jeopardizes both the nurse and patients. Alternatively, nurse administrators can deal with the problem by recognizing its prevalence in society, educating their personnel, providing support systems for staff, and establishing controls. By choosing this latter course of action, nurse managers evidence humanity and concern for patients, the profession, and individual practitioners. PMID- 2911048 TI - Self concept: improving the image of nursing. PMID- 2911049 TI - Developing investigators who will generate clinically relevant science. PMID- 2911050 TI - Computers: meeting the challenge of the information age. PMID- 2911051 TI - Choosing your treatments with care. PMID- 2911052 TI - Prognostic evaluation of ameloblastoma based on histologic and radiographic typing. AB - Ninety-one patients with ameloblastoma of the mandible were studied. Among the 23 patients treated with radical surgery the recurrence rate was 8.7%, whereas the rate of 45.65% in the 68 conservatively treated patients. The prognoses of the patients treated by conservative surgery were analyzed based on the histologic and radiologic criteria of each lesion. The recurrence rate was significantly higher in the follicular type (56.8%) than in the plexiform type (32.3%). Recurrence was seen more frequently in the multilocular or soap bubble type (60.7%) than in the unilocular type (35.0%). When the recurrence rate was compared between patients aged less than 20 years and patients aged greater than or equal to 20 years, younger patients had better prognoses. It was concluded that there is a prognostic value in the histologic, radiographic, and age factors. PMID- 2911053 TI - The relationship between cervical cysts and tonsillar carcinoma in adults. AB - An investigation of the clinical results in 42 patients with lateral cervical cysts is presented. Fine needle aspiration biopsy suggested malignancy in three cases. After surgical removal, another six cases of malignancy were revealed by histologic examination. In six of the nine cases of malignancy, an ipsilateral tonsillar carcinoma was found on routinely performed tonsillectomy. However, the clinical appearance of the tonsils was normal in four of these patients. Analysis of all patients according to age revealed that the malignancy rate was 80% among those aged greater than 40 years. It is suggested that tonsillectomy for histologic examination should be performed routinely when lateral cervical cysts are removed in adults. PMID- 2911054 TI - Magnetic resonance imaging of partial temporomandibular joint disc displacement. AB - Unilateral magnetic resonance imaging (MRI) of the symptomatic temporomandibular joint (TMJ) was performed on 55 patients. The position of the articular disc in relation to the condyle was established on sagittal images. Particular attention was paid to partial or complete anterior positioning of the disc. MRI was correlated with clinical and, in 33 cases, surgical findings. The concept of partial anterior displacement may be useful in relation to treatment planning. PMID- 2911055 TI - An assessment for auriculotemporal syndrome following temporomandibular joint surgery through the preauricular approach. AB - Twenty temporomandibular joints (TMJs) were operated on for the correction of arthrographically confirmed internal derangements using a modified preauricular approach. Postoperatively, three of the 20 patients tested exhibited auriculotemporal syndrome as deduced from a starch-iodine test. The manifestation was subclinical and consisted of sweating only over the distribution of the auriculotemporal and great auricular nerves in response to a gustatory stimulus. The response was variable from patient to patient. PMID- 2911056 TI - Cephalometric norms for orthognathic surgery in black American adults. AB - Normal values for the Cephalometrics for Orthognathic Surgery (COGS) analysis for American black adults were developed in this study. The cephalometric radiographs of 33 black American adults with ideal dentitions were analyzed, and a statistical description of their hard and soft tissue cephalometric measurements is presented. In addition, mean values for black American adults were compared with those of white American adults. In black subjects, there was greater maxillary skeletal prognathism, skeletal lower face height, skeletal facial convexity, lower incisor proclination, anterior dental heights, upper and lower lip lengths, and soft tissue thickness of the lips and chin than in white subjects. There was less nasal depth and projection, less bony chin depth, and a smaller nasolabial angle in black subjects. The results of this study may be useful in providing racially specific cephalometric values for diagnosis and treatment planning for orthognathic surgery in American black adults. PMID- 2911057 TI - The in vivo behavior of gentamicin-PMMA beads in the maxillofacial region. AB - Gentamicin-PMMA beads were placed in maxillofacial wounds of ten dogs, and gentamicin levels from wound drain sites, serum, and urine were measured by radioimmunoassay. The results indicate extremely high wound and modest urine levels (which decrease exponentially) concurrently with negligible serum levels of gentamicin. The results of this study of a highly vascularized area were similar to other studies in which beads were placed in avascular areas. PMID- 2911058 TI - Malpractice litigation: the deposition. AB - A deposition is an important tool in the discovery process that can strengthen or weaken a defendant's position. It is critical that defendants understand the purposes and strategy of a deposition so that they can prepare themselves adequately. PMID- 2911059 TI - Anaphylactoid reaction to vancomycin: report of a case. AB - Although vancomycin produces excellent prophylaxis against staphylococci, the danger of hypotension, whether secondary to anaphylactoid response or myocardial depression, exists. Therefore, recommendation for the use of vancomycin before dental procedures must include the precaution of administration in a dilute solution over 30 minutes, with frequent monitoring of BP and heart rate. PMID- 2911060 TI - Myoglobinuria and elevated serum enzymes associated with partial glossectomy under enflurane anesthesia in a patient with muscular dystrophy. PMID- 2911061 TI - Spontaneous removal of foreign bodies from the maxillary sinus: report of a case. PMID- 2911062 TI - Treatment of a mandibular fracture in a neonate. AB - The treatment and long-term follow-up of mandibular fracture in a neonate have been presented. Early treatment can prevent the need for later extensive and expensive reconstructive surgery. PMID- 2911063 TI - Chondroma of the tongue. PMID- 2911064 TI - A simplified technique for percutaneous rigid fixation of sagittal ramus osteotomies. PMID- 2911065 TI - Modification of the interocclusal splint for orthognathic surgery. PMID- 2911066 TI - Temporomandibular joint retractors. PMID- 2911067 TI - Parish nursing's pioneer. A JCN interview. PMID- 2911068 TI - Profile of a young movement. PMID- 2911070 TI - Church nurse--caring for a congregation. PMID- 2911069 TI - Nursing's only hope. PMID- 2911071 TI - At the breaking point. When should an overworked nurse bail out? PMID- 2911072 TI - Visiting granddaddy one last time. PMID- 2911073 TI - American Public Health Association Resolution 8701: irrational response to the fear of the spread of the virus that causes AIDS. PMID- 2911074 TI - Oral hygiene instruction and health risk assessment in dental practice. AB - We studied oral hygiene instruction given to 109 patients in 19 Washington State dental practices to investigate the extent to which therapists targeted their efforts toward patients with high disease risk. Patients were examined prior to instruction and prophylaxes. Therapists' instructions were tape-recorded and their content analyzed: therapists' expectations were scored. There were no statistically significant associations between patients' initial plaque levels and the process/content of the oral hygiene instructions delivered. On average, therapists spent 9.4 minutes of each prophylaxis session discussing oral hygiene. Therapists were judged more genuine with those patients for whom they had higher expectations of compliance, i.e., those with less plaque and low disease risk. We conclude that dental practitioners were not employing effective risk assessment strategies in selection of patients most in need of intensive instructional efforts. PMID- 2911075 TI - How effective is oral hygiene instruction? Results after 6 and 24 weeks. AB - We studied the clinical effectiveness of oral hygiene instruction given to 71 "high" plaque patients in 19 Washington State dental practices to determine the extent of plaque reduction. Patients were examined prior to instruction and prophylaxis. Therapist instructions were tape-recorded and content analyzed, and therapists' expectations were scored. Patients were surveyed as to oral health behaviors and general health habit characteristics. Only 20 of 71 (28%) initially "high" plaque patients had reduced mean plaque scores to 1.0 or less at six weeks. An additional 13 percent had deteriorated plaque levels at 24 weeks. We concluded that therapists did not consistently follow principles of effective instruction and often overestimated their effectiveness. Determinants of relapse involve the educational process, the patients' oral status, and patients' life situations. PMID- 2911076 TI - Oral health knowledge and sources of information among elementary schoolchildren. AB - The dental health knowledge and sources of health information of 848 elementary schoolchildren (aged 9-12) in southwestern Michigan were assessed. Demographic parameters (education level, percent below poverty level, median income level) of the area were similar to state and national averages. The children were found to have some knowledge of caries and periodontal disease prevention, yet basic misconceptions were evident. More than one-third of the children thought that plaque should only be removed by a dentist. While 75 percent of the subjects knew that fluoride protected teeth from decay, only 4 percent of the children identified fluoridated water as the best source of this preventive agent. Knowledge of pit and fissure sealants was limited. Extent of correct dental knowledge was not related to age, sex, or mean DMFS scores. Children who answered the most questions correctly named parents and family as their source of information; dentist's office was the second most frequently mentioned source. Findings suggest a need to correct basic misinformation about dental health and to inform children about current efficacious preventive agents. PMID- 2911077 TI - Uses and abuses of the news release/press conference. PMID- 2911078 TI - Oral health knowledge and attitudes of elementary schoolteachers in Michigan. AB - Teachers at elementary schools in two areas (urban and rural) of Michigan were surveyed to determine their sources of information about oral health and their knowledge and attitudes about dental diseases and disease prevention. Questionnaires were completed by 404 teachers (62% response rate). More than 80 percent of respondents from both areas were female. Demographic characteristics that were significantly different between groups included: median ages of urban and rural respondents (P less than .01), median numbers of years in teaching (P less than .01), and median years in residence (P less than .03). Despite these differences, responses to the questionnaire varied little. For both groups, the most frequently cited sources of information about dental health were dentist's office (82%), followed by magazines and books (74%). The teachers considered preventing tooth decay as the most important reason for good oral hygiene. When asked to rank the effectiveness of ten methods of preventing caries in children, teachers ranked efficacious methods such as fluoridated water and pit and fissure sealants lower than making regular dental visits and reducing intake of sugared foods. Asked to rank the most effective method for children to receive fluoride, urban respondents ranked fluoridated water first, while rural respondents ranked this measure third. Findings suggest that teachers' knowledge about oral health and current methods of prevention is incomplete, is inaccurate in some instances, and varies little by geographic area. PMID- 2911079 TI - Health ecology and dental education. PMID- 2911080 TI - Assessment of a dental disease prevention program after three years. AB - This assessment compared routine data on selected clinical services provided within the Oklahoma City Area of the Indian Health Service during the first six months of fiscal year 1984, prior to implementation of a program emphasizing oral health promotion and disease prevention, to comparable data from 1987. The assessment revealed: similar absolute numbers of routine examinations and completed treatment among children; a 10 percent increase in total visits for persons of all ages, accomplished with comparable numbers of dental personnel; and an increase in the percent of services that were preventive, as well as a concomitant decrease in basic restorative services. The ratio of pit and fissure sealants to one-surface amalgam restorations was reversed dramatically. Although counts of services rendered do not measure oral health status directly, some conclusions are warranted. Clinical dental personnel can be reoriented to devote an increased proportion of available patient care time to primary preventive services, accomplishing a substantial increase in these services. That increase is associated with a corresponding decrease in the proportion of basic restorative services. PMID- 2911081 TI - Eruption pattern of permanent molars: implications for school-based dental sealant programs. AB - Dental caries remains a prevalent, chronic disease of childhood. The preponderance of dental caries is located on the pit and fissure surfaces of teeth, an area where dental sealants are most effective in preventing this malady. In the school year 1987-88, 4,879 Ohio schoolchildren participated in an assessment of dental health. Grades chosen for this assessment included 1, 2, 3, 6, 7, 8, and 11. This study focuses on eruption of first and second permanent molars in development of a timing strategy for placement of occlusal sealants in a school-based program. An eruption score was developed for the determination of the first or second molar eruption status for each child. The data were analyzed for grade, sex, race, locale, fluoridation status, and percent of children on free or reduced-cost lunch programs. Analyses were performed on 2,215 children in grades 1-3 and 1,840 children in grades 6-8. Fifty-seven percent of first graders had all first permanent molars sufficiently erupted for sealant placement on the occlusal surface. Likewise, 23.6 percent of sixth graders had sufficient occlusal exposure on the second molar. Females showed an earlier eruption pattern than males for both first (P less than .05) and second (P less than .001) molars. Black children preceded white children only in the eruption of the second molar (P less than .001). This study provides dental public health decision makers with state-specific information on the earliest time to initiate a school-based occlusal sealant program.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2911082 TI - Interaction between anti-Gal and human tumor cells: a natural defense mechanism? PMID- 2911083 TI - Smoking policies among private employers and public agencies in Texas: a statewide analysis. AB - The present study examined the prevalence, correlates, and perceived impact of smoking policies among private employers and public agencies in Texas. An identical survey instrument was administered to two groups of Texas employers: a random sample of private industries and all state agencies (excluding universities). Response rates were 62% (n = 420) for private industries and 73% (n = 130) for public agencies. Fifty-two percent of state agencies and 53% of private employers reported having a smoking policy, with the majority of policies having been implemented since 1986. Concern about employees' health or comfort was the most important reason for implementing a policy for both state agencies and private employers. Both groups believed that implementation of a policy resulted in fewer complaints from employees and less smoking in the workplace but had less impact on productivity or morale. This study on the prevalence of smoking policies in the workplace is the first to document that the majority of surveyed employers have a restrictive smoking policy in place. In addition, this study found minimal differences in the prevalence, rationale, and perceived benefits of smoking policies between private employers and state agencies. PMID- 2911084 TI - Reduction of tumor blood flow by flavone acetic acid: a possible component of therapy. AB - Flavone acetic acid (FAA) is active against normally refractory murine sc tumors. Clinical studies are disappointing despite achievement of plasma profiles associated with the antitumor murine activity in man. To clarify the mechanism of action, we have followed histologic changes, tumor blood volume, and drug concentrations in a well-differentiated, slow-growing cystic adenocarcinoma in mice. FAA causes massive tumor necrosis beginning 2 hours after treatment. Tumor plasma volumes are reduced by 2 hours after treatment and tumor blood vessels are shutdown, which suggests that tumor vasculature plays a role in the dramatic response of sc tumors in pure-strain male NMRI mice. PMID- 2911085 TI - Selective mutagenic activation by cytochrome P3-450 of carcinogenic arylamines found in foods. AB - Heterocyclic arylamines found in cooked foods including fish and beef are potent mutagens and carcinogens. The purpose of this investigation was to determine the specificity of cytochromes P1-450 and P3-450 toward the metabolic activation of these arylamines. We used a novel mutagenicity test system which combined human cells expressing either recombinant cytochrome P1-450 or P3-450 with Salmonella typhimurium to score mutants. Cytochrome P3-450, a single isoform of the cytochrome P-450 supergene family, bioactivated these food mutagens. Cytochrome P1-450 showed little or no activation of these arylamines but was the isoform predominantly responsible for the activation of the aromatic hydrocarbon benzo[a]pyrene-7,8-diol. This assay system should serve to define the specificities of individual cytochromes P-450 in the metabolic activation of carcinogens. PMID- 2911086 TI - Pressure wave injuries to rat dorsal root ganglion cells in culture caused by high-energy missiles. AB - A high-energy missile impact in an extremity of an animal creates a shock wave which is rapidly dispersed as a burst of oscillating pressure waves that traverses the entire body causing local, regional, and distant injuries. The present study was performed on dorsal root ganglion (DRG) cells, cultured for 3 weeks, to elucidate the cellular mechanism for damage of nerve cells, using a simplified test system. A model system was developed allowing exposure of DRG cultures to a burst of high-frequency oscillating pressure waves, comparable to those recorded in animals after high-energy missile extremity impact. The pressure waves were induced by impact of a high-energy missile in a rubber tube filled with water, in which nerve cell cultures were kept in a closed rubber glove filled with tissue culture medium. The pressure waves had a duration of 0.5 1.5 ms and a frequency spectrum ranging from 0-250 kHz. Within minutes the neurites showed changes in their microtubules. In addition, varicosities, enriched with tubulin immunoreactive material, became irregularly studded along the nerve cell processes. Scattered DRG cells were initially permeable to the marker complex Evans-blue albumin (EBA), used as an indicator of the ability of the plasma membranes to exclude proteins. After 6 hr, however, almost every DRG neuron was intensely stained by EBA. Concomitantly, there was swelling of the nerve cell cytoplasm and organelles, and, to a variable extent, neurofilament tangles were observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2911087 TI - Repair of the isolated cut flexor digitorum profundus tendon under intravenous regional anaesthesia. AB - Intravenous regional anaesthesia proved to be an effective anaesthetic agent for the repair of isolated cut flexor digitorum profundus tendons. Twenty-five patients underwent primary repair, of whom 20 were assessed 1 year later. Overall results were satisfactory regarding movement at the distal joint. Five of the cases were missed at initial examination and the repair carried out longer than 1 week from the injury. In view of the generally accepted poor initial diagnosis in the Emergency Department for the isolated flexor tendon lesion, exploration under a simply performed local anaesthetic block has advantages where the diagnosis is in doubt. The main operative problem with this technique was the venous ooze which occurred during the operation, and this could be a contraindication to its use for more complicated hand surgery. PMID- 2911088 TI - Secondary infection of post-traumatic pulmonary cavitary lesions in adolescents and young adults: role of computed tomography and operative debridement and drainage. AB - Secondary infection of post-traumatic cavitary lung lesions is unusual. This report describes the clinical course of four patients who sustained severe blunt chest trauma and developed pulmonary pseudocysts that became foci for systemic sepsis. All four patients were adolescents or young adults. Hemophilus species and aerobic Gram-negative rods were the predominant pathogens recovered. Computed tomography of the chest was instrumental in establishing the diagnosis in each case. Despite appropriate antibiotic therapy, all four patients remained septic for weeks. One of the patients died as a result of this infectious process. One patient underwent successful operative debridement and drainage of the involved lung and pleural space. Because infected traumatic pseudocysts may not respond like typical lung abscesses to appropriate antibiotic management, early exploratory thoracotomy should be considered in those patients with prolonged fever and pulmonary deterioration. PMID- 2911089 TI - Mitral and tricuspid valve rupture from blunt trauma sustained during a motor vehicle collision. AB - The incidence of mitral valve injury resulting from blunt trauma is low. This report presents the case of a 36-year-old male who survived the rupture of both his mitral and tricuspid valves after striking the steering wheel during a motor vehicle accident. Echocardiograms were used to make the diagnosis. PMID- 2911090 TI - Rupture of the liver and right hemidiaphragm presenting as right hemothorax. AB - A young man hit by a car while riding his motorcycle presented with reversible hypotension, a compression fracture of C6, fractures of the left femur and of ribs 9-12 on the right, and right hemothorax. A falsely negative peritoneal lavage delayed laparotomy, which, when done, demonstrated two right diaphragmatic rents with bleeding into the right chest from a severe liver injury. Presentation of this case demonstrates that while peritoneal lavage is an excellent way to exclude intraperitoneal hemorrhage following blunt abdominal trauma, false negative results may occur in the setting of hemorrhage with diaphragmatic rupture. PMID- 2911091 TI - A unique closed abduction-external rotation ankle fracture. AB - A unique closed abduction-external rotation ankle fracture with a combined medial malleolar fracture and avulsion of the deltoid ligament is presented. Thorough literature search has not revealed a similar case. This report is well documented with an operative photograph, radiographs, and a 20-month followup. A mechanical basis for such an injury pattern is described. The magnitude and complexity of the injuring forces applied to the ankle region in road trauma may lead--as in this presentation--to unusual injury combinations. PMID- 2911092 TI - Triple dislocations in the index finger. AB - A dislocation of both interphalangeal joints in a single finger is a rare injury. Although there have been some reports in the English-language literature of such injuries (4, 6, 7, 12) and one report of a double dislocation in the thumb (3), we found no published case studies of triple dislocations in the same digit. PMID- 2911093 TI - Acromioclavicular dislocation associated with fracture of the coracoid process. AB - Two cases of acromioclavicular dislocation associated with fracture of the coracoid process are described. This association is unusual and the coracoid fracture may only be recognised on an axillary radiograph of the shoulder. Both the cases were treated conservatively, with good results. The management and outcome of other cases described in the literature are reviewed and discussed. PMID- 2911094 TI - Repair of suprahepatic caval lesions under extracorporeal circulation in major liver trauma. AB - A case of major hepatic injury with associated juxtahepatic trauma is reported. Repair of the injuries was effected with the aid of extracorporeal circulation. This aided exposure of the bleeding site while at the same time minimizing blood loss. Hypothermia is an added benefit of this approach, decreasing the risk of hepatic ischaemia. PMID- 2911095 TI - Acute carpal tunnel syndrome in a patient taking coumadin. AB - This is a case report of a 66-year-old female who had been taking coumadin for 4 weeks for deep vein thrombosis. She developed acute carpal tunnel syndrome following minor trauma to her wrist. After conservative therapy failed to relieve her symptoms she underwent release of her carpal tunnel with resolution of her symptoms. While there are many patients taking coumadin, its association with acute carpal tunnel syndrome is quite rare: we were only able to find only one other reported case in the literature. While one is tempted to treat these patients conservatively, operative therapy may be indicated. PMID- 2911096 TI - The 'occult' compartment syndrome. AB - Two cases of compartment syndromes after tibial fractures are presented in patients who had no sensation in the involved compartments. The absence of any clinical symptoms in these patients emphasizes the need for routine monitoring of intra-compartmental pressure in this select group of patients. PMID- 2911097 TI - The 'occult' compartment syndrome. PMID- 2911098 TI - Outcome of acetabular fractures: a 7-year follow-up. AB - A 10-year series of 75 acetabular fractures has been reviewed. Traffic accidents (61%) and falls from heights (20%) were the most common etiologic factors. In 80% of the patients multiple injuries were recorded. Seventeen patients were treated operatively. Forty-three patients were examined clinically and radiologically at an average of 7 years after the accident. The outcome of posterior wall fractures was usually good. Most of the fair and poor results occurred in the group of transverse fractures, in which conservative treatment did not accurately align the fracture dislocation. Operative treatment is suggested in both-column fractures and severely dislocated transverse fractures. PMID- 2911099 TI - Lethal horse-riding injuries. AB - Riding accidents can be of a serious nature. Knowledge of risk factors is of essential value in the prevention of injuries. From the years 1969 through 1982 a series of 53 lethal riding injuries is analysed with reference to the rider, the horse, and the environment. Craniocerebral injuries dominate in this series, indicating the importance of adequately protecting helmets. Among the victims the female sex is dominating before the age of 25 and the males above this age. Older horses are less frequently involved in these accidents than younger ones. A long training period for riders under surveillance of a teacher is of outmost importance. Outdoor riding should be recommended only to experienced riders. PMID- 2911100 TI - The epidemiology of trauma in an intensive care unit in Bahrain. AB - Injuries resulting from trauma are over-represented in Bahrain's intensive care unit beds. Using data from 1984 and 1985, this study examines the most severe etiologic agents and high-risk population groups among ICU trauma patients. Road traffic accidents were the principal cause of admission, accounting for 57% of all injury admissions. Most occurred in pedestrians suffering from severe head injury. Poisonings were the second largest category, followed by falls. In comparison with medical cases admitted to the ICU during the same 2-year period, the trauma cases included a disproportionate number of children and males in their most productive years of life, further adding to the economic burden which injuries have inflicted on this small country. The authors call for a new approach, namely passive prevention such as environmental modifications and legislation and tertiary prevention such as improvement of the country's underutilized ambulance service. PMID- 2911101 TI - Chest injuries sustained in severe traffic accidents by seatbelt wearers. AB - In Finland during the period 1972-1985, there occurred 3,468 severe traffic accidents in which one or more of the drivers or passengers sustained an injury leading to a fatal outcome within 30 days. Of the victims who had been wearing seatbelts, 207 had fatal and 73 had severe chest injuries. The four leading causes of fatalities resulting from chest injuries were ruptures of the aorta (37%), ruptures of the heart (28.4%), and bilateral lung contusions (31.1%) or lacerations (15.5%). Seatbelt wearers with heart ruptures more often had concomitant rib fractures, lung injuries, and sternum fractures than those who had sustained ruptures of the aorta. The side of rib fractures was associated with the victim's location in the car, drivers seated on the left having more right-sided and right front passengers more left-sided rib fractures. In addition to chest injuries, 87% of the victims had other concomitant injuries, the most common abdominal injuries being liver injuries (40.2%) and spleen ruptures (26.5%). In seatbelt wearers chest injuries with a fatal outcome appear to be caused by impacts of exceptional severity, since in more moderate accidents seatbelt wearing has proved to save lives. PMID- 2911102 TI - Treatment of acute penetrating injuries of the spine: a retrospective analysis. AB - A retrospective review of 160 cases of penetrating spinal injury (PSI) was undertaken to assess the benefits and risks of operative treatment. Criteria for operation included incomplete deficits, worsening neurological status, and associated visceral perforation. Of the 160 cases, 142 had gunshot wounds (GSW) and 18 had stab wounds (SW). Laminectomy, with or without intradural exploration, was undertaken in 23% of cases. No significant differences in outcome were found between the surgical and nonsurgical groups. Meningitis, CSF leakage, and wound infections were complications that occurred more often in the surgically treated group (22%) than the conservatively managed group (7%). It has not been possible to demonstrate a benefit of surgery in PSI in this retrospective study. A prospective study is proposed that would allow better control of the variables affecting outcome. PMID- 2911103 TI - The effect of viable omentum on early bile leakage and healing of liver lacerations. AB - In order to determine if omental tissue accelerates the healing of liver lacerations, simulated bile leakage and collagen biosynthesis were studied in 53 rabbits. After creating a standardized complex liver laceration, hemostasis was obtained by vessel ligation and electrocoagulation. The wound was either left open (OP) or viable omentum sutured to its base (OM). Simulated bile leakage was noted in all of eight animals (four OM, four OP) studied on day of injury. None of 18 OM and two of 17 OP animals demonstrated extravasation of dye from the wound on the second and third postinjury day (N.S.). The ratio of mRNA for alpha 1(I) procollagen/actin, used as an indicator of wound healing, was 56.3 +/- 7.8 for OM and 50.6 +/- 12.1 for OP at the wound edge, and 63.5 +/- 18.6 and 69.2 +/- 7.5, respectively, for RNA isolated from the scar (N.S.). For alpha 1(III) procollagen mRNA, the ratio was 23.9 +/- 3.5 for OM and 22.4 +/- 8.3 for OP at the wound edge, and 32.4 +/- 6.5 and 31.8 +/- 7.9, respectively, for RNA isolated from the scar (N.S.). There was no difference in the scar hydroxyproline content between the two repair methods. In this model of hepatic injury and repair, bile leakage was minimal by the second postinjury day with both repair methods. Placing the omentum in liver lacerations did not contribute to accelerated wound healing as measured by simulated bile leakage and collagen biosynthesis. PMID- 2911104 TI - A microcomputer program for coding external cause of injury. AB - The publication of Injury in America emphasized a renewed interest in the scientific study of trauma. Collection and analysis of population-based data were viewed as necessary prerequisites for the establishment and evaluation of injury prevention programs. While it was noted that there is an existing broad-based gathering of injury mortality information, it was also made clear that there is a paucity of systematically collected morbidity data. A fundamental step toward correcting this deficiency is to identify and adopt a uniform system for coding causes of injury morbidity that is compatible with the large body of mortality data currently being collected. This paper describes a microcomputer-based program, which is intended to aid in the selection of External Cause of Injury Codes (E-codes). It is designed for coding both fatal and nonfatal injury causes and is appropriate for use in the hospital setting. The system is a modification of the one currently used for coding all injury deaths in the United States. PMID- 2911105 TI - The use of P.O.P. integrated transfixation pins as an improvisation on the Hoffmann's apparatus: contribution to open fracture management in the tropics. AB - With consideration to the relatively high complication rate of internal fixation methods in the management of open fractures, 16-36% (17), the use of 'fixateur externe' or Hoffmann's apparatus is widely accepted as the best method of management. We do not have this valuable apparatus in our hospital due to the socioeconomic constraints typical of developing countries. We found a valuable improvisation in the use of Bohler's transfixation methods and even to the extent of achieving osteotaxis and ambulation. The management method is described with our positive experiences of its use in 28 cases of open fractures and other bone and joint afflictions. The advantages and disadvantages of the method are discussed. The method is recommended as a valuable substitute for the 'fixateur externe.' PMID- 2911106 TI - Renal trauma and hypertension. AB - A retrospective study (1972-1983) was made of 622 consecutive patients who suffered renal trauma, in order to assess the incidence and prevalence of post traumatic renal hypertension. In 435 (76%) of the 569 survivors long-term followup data and blood pressure recordings were obtained, 13 months to 12 years after trauma (mean, 5.6 years). Renal trauma could not be linked to an increased incidence of hypertension: on first control, only 94 patients (21%) demonstrated a casual elevated blood pressure (greater than 140/90 mm Hg). The presence of a fixed hypertension was validated in only 14 patients. Twelve of them were extensively screened in the Department of Internal Medicine. In none of these patients could a definite relationship between hypertension and renal trauma be documented. Furthermore, an extensive review was done of 223 cases of post traumatic renal hypertension reported in the literature from 1951 until 1984. Careful analysis of these previously described cases (71 publications) leads us to criticize the widespread accepted cause-effect condition with regard to post traumatic renal hypertension. It is concluded that adequate management of renal injuries with early diagnosis and individualised surgical treatment can prevent this extremely rare complication. PMID- 2911107 TI - Quantitative measurement of bleeding following hypertonic saline therapy in 'uncontrolled' hemorrhagic shock. AB - The effect of small volume hypertonic saline in "uncontrolled" hemorrhagic shock (UCHS) induced by partial resection of the tail was studied in rats. The rats were divided into three groups: in group 1 (n = 15) 10% of the terminal portion of the animal's tail was resected to induce UCHS. In group 2 (n = 14) UCHS was induced as in group 1 and after 5 min 5 ml/kg NaCl 0.9% (NS) was infused intravenously. In group 3 (n = 22) UCHS was induced as in group 1 and after 5 min, 5 ml/kg NaCl 7.5% (HTS) was infused intravenously. Resection of the animal's tail was followed by bleeding of 3.5 +/- 0.3 ml within 5 min, fall in MAP to 63 +/- 4 torr (p less than 0.001) and pulse to 300 +/- 18 per min (p less than 0.05). The amount of bleeding, fall in MAP, and pulse after 5 min were similar in the three groups. Further blood loss after 60 min in group 1 was 3.7 +/- 0.8 ml, in group 2, 2.9 +/- 0.5 ml, and in group 3, 6.5 +/- 0.8 (p less than 0.01). Increased bleeding in group 3 showed two peaks: an early peak of 1.3 +/- 0.2 ml after 15 min (p less than 0.05) and a late peak of 1.2 +/- 0.4 ml at 45 min (p less than 0.05) and 1.7 +/- 0.5 ml at 60 min (p less than 0.01). MAP fell after 60 min to 54 +/- 7 torr in group 1 (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2911108 TI - Zero-time prehospital i.v. AB - Advances in prehospital stabilization and resuscitation of traumatized victims continue to have an impact on morbidity and mortality. Certain aspects of Advanced Trauma Life Support still remain controversial. Recent reports have questioned the usefulness of IV's started in the prehospital phase both because of delay in transport and because of the actual or theoretical lack of adequate volume infusion during transport. If IV lines can be started while an accident victim is en route to the hospital with no delay in transport, then much of the argument against prehospital IV's becomes irrelevant. From October 1985 through November 1986 we prospectively studied IV access attempts in 350 consecutive patients. Overall IV's started at the scene were 77% successful (n = 70) and en route 81% (n = 213) of attempts were successful. Of those with BP less than 100 mm Hg, there were 66% successful on-scene attempts and 72% successful en-route attempts. Protocols for IV administration in non-trapped patients should initiate IV access only en route to the hospital while the ambulance is moving. Even if delay at the scene is minimal, it is not possible to justify any delay, since IV's can be successfully instituted en route. PMID- 2911109 TI - Evidence of increased gluconeogenesis during hemorrhage in fed and 24-hour food deprived rats. AB - Food withdrawal 24 hr before hemorrhage has been shown to increase experimental post-hemorrhage mortality, and survival is associated with the degree of hyperglycemia. Lack of hyperglycemic response has been attributed to depleted glycogen reserves after 24-hr food withdrawal. To investigate the effect of short term food deprivation on glucose metabolism during hemorrhagic stress, glucose production (rate of appearance, Ra), glucose uptake (rate of disappearance, Rd), glucose clearance, and glucose recycling were investigated in fed and 24-hr food deprived rats under basal conditions, and during hemorrhagic hypotension using 3 H3-U-C14-glucose. During hemorrhage, blood glucose levels were higher in fed rats. Hemorrhage induced a decrease in glucose clearance irrespective of nutritional state in both 24-hr starved animals and rats in the postprandial state. Calculated glucose recycling increased in both groups after hemorrhage. The results indicate that hemorrhagic stress induces a rapid increase in gluconeogenesis, as reflected by increased glucose recycling. PMID- 2911110 TI - Carotid artery injuries: experience with 124 cases. AB - This is a retrospective study of 124 patients with carotid injuries. The common carotid artery was injured in 84% of the patients. Associated trauma to the internal jugular vein was present in 26%. Most patients (56%) were dead on arrival to the hospital and of those who were operated on, the mortality was 22% (overall mortality, 66%). All operative mortalities had severe shock or neurologic deficits on admission. We performed repair on all patients with preoperative neurologic deficits and the mortality was 64%. The use of a shunt did not influence the prognosis. We believe that there is no place for an emergency angiogram in order to diagnose a carotid injury or to plan the operation. PMID- 2911111 TI - The injury potential and lethality of stab wounds: a Folsom Prison Study. AB - The morbidity and mortality of stab wounds is unknown since much of the data is unobtainable. Folsom Prison, a closed system with respect to population at risk and medical care, represents a unique situation where all stab wounds and subsequent care are accounted for. A retrospective review of stabbing incidents at Folsom Prison identified 751 wounds in 270 prisoners. Overall mortality was 3%. Thirty-five per cent of the victims were hospitalized. The overall chance of serious injury, defined as an assault victim requiring more than cleansing and suturing of his wounds, was 25%. The most common procedures were tube thoracostomy (performed 36 times) and celiotomy (performed 31 times). We believe that this is the first study of its kind involving a closed population to accurately assess the overall morbidity and mortality of stab wounds. The 3% mortality and the 25% requiring a procedure beyond suturing reflects the low injury potential long clinically suspected in stab wounds. PMID- 2911112 TI - Evidence for a ligation step in the DNA replication of the autonomous parvovirus minute virus of mice. AB - Newly replicated DNA of the autonomous parvovirus minute virus of mice was pulse labeled with 32PO4 during the time of maximal viral DNA replication in highly synchronized A9 cells. The subsequent processing of viral DNA-protein complexes was monitored during a chase period with no label. Several distinct classes of duplex replicative-form and progeny single-stranded DNA molecules were characterized and found to accumulate at different times during infection. Analysis of the terminal structures associated with these various forms provided new insights into the mechanism by which viral DNA replicates and, in particular, suggested that interstrand ligation occurs during this process. PMID- 2911113 TI - Drosophila S virus is a member of the Reoviridae family. AB - The S character of Drosophila simulans, the absence or malformation or both of bristles and other cuticular structures, was described by Comendador (Drosophila Inf. Serv. 55:26-28, 1980). Its characteristics (maternal transmission, low pathogenicity, and sensitivity to temperature) suggested the existence of a virus as the causative agent. Indeed, reoviruslike particles were found in subcuticular cells of S individuals, and its association with S phenotypic expression was shown. This virus was called Drosophila S virus (DSV) (C. Louis, M. Lopez-Ferber, N. Plus, G. Kuhl, and S. Baker, J. Virol. 62:1266-1270, 1988). We report here the purification and analysis of some properties of DSV particles, the morphology (spherical, 60 nm in diameter with an electron dense central core and less dense shell) and genome composition (double-stranded RNA divided into segments), which classify DSV as a new member of the family Reoviridae. PMID- 2911114 TI - Arrangement of repetitive sequences in the genome of herpesvirus Sylvilagus. AB - Herpesvirus sylvilagus is a lymphotropic (type gamma) herpesvirus of cottontail rabbits (Sylvilagus floridanus). Analysis of virion DNA of herpesvirus sylvilagus has revealed that the genome consists of one stretch of about 120 kilobase pairs of internal, unique DNA flanked by a variable number of 553-base-pair tandem repeats. The G + C content of the repetitive DNA is extremely high (83%), as determined by sequencing. The organization of the herpesvirus sylvilagus genome is, therefore, similar to that of the primate lymphotropic viruses herpesvirus saimiri and herpesvirus ateles. PMID- 2911115 TI - Genome structure of cottontail rabbit herpesvirus. AB - The genome structure of a herpesvirus isolated from primary cultures of kidney cells from the cottontail rabbit Sylvilagus floridanus was elucidated by using electron microscopy and restriction enzyme analysis. The genome, which was about 150 kilobase pairs long and which had an average G + C composition of 45%, consisted of two regions with unique base sequences (54 and 47 kilobase pairs) enclosed by reiterations of a 925-base-pair sequence with a variable copy number. The internal repeats were in opposite polarity with respect to the terminal repeats, and both unique regions underwent inversion. The nucleotide sequence of the repeat unit was determined, and virion DNA termini were precisely localized within this sequence. Elements showing homology with the cleavage-packaging signals common to other herpesviruses were detected. The data indicate that this virus is different from the previously described herpesvirus sylvilagus. PMID- 2911116 TI - Adenovirus early region 4 is essential for normal stability of late nuclear RNAs. AB - H2dl808 is a deletion mutant of adenovirus type 2 lacking most of transcriptional early region E4. In most normal adenovirus host cells this virus displayed a complex mutant phenotype that included a dramatic reduction in the level of cytoplasmic late RNA, a corresponding defect in late protein synthesis, and a 5- to 10-fold defect in viral DNA accumulation. H5dl1004 is a deletion mutant of adenovirus type 5 that also lacks a portion of E4. It exhibited a reduction in levels of cytoplasmic late RNAs that was somewhat less severe than that of H2dl808 and a corresponding late protein synthetic defect but no defect in the production of viral DNA. In addition to the defect in the accumulation of late cytoplasmic mRNAs, HeLa cells infected by either H2dl808 or H5dl1004 showed substantially reduced levels of viral RNAs in their nuclei at late times after infection. Both mature mRNAs and apparent mRNA precursors were affected. The late transcription rates of the deletion mutant viruses were similar to that of wild type virus. These results suggest that the underaccumulation of RNA in H2dl808- and H5dl1004-infected cells is caused by a reduction in the stability of viral RNA in the nucleus, and they implicate E4 products in a novel aspect of the regulation of viral gene expression. PMID- 2911117 TI - Redundant control of adenovirus late gene expression by early region 4. AB - A series of human adenovirus type 5 derivatives carrying deletion mutations in early region 4 (E4) were constructed and characterized with respect to viral late protein synthesis, viral cytoplasmic late message accumulation, viral DNA accumulation, and plaquing ability. Viral late protein synthesis was essentially normal in cells infected by mutants expected to produce either the E4 open reading frame (ORF) 3 product or the E4 ORF 6 product. In cells infected by mutants lacking both ORF 3 and ORF 6, late protein synthesis was dramatically reduced. The basis for this reduction appears to be a concomitant reduction in cytoplasmic late message levels. Our results suggest that the products of ORFs 3 and 6 are redundant, since they are individually able to satisfy the requirement for E4 in late gene expression. Two of the mutants examined were defective for viral late protein synthesis but showed no measurable defect in viral DNA accumulation. The defect in late gene expression is not, therefore, a reflection of a primary defect in viral DNA synthesis. Finally, mutants expected to express ORF 3 or ORF 6 formed plaques with normal or only modestly reduced efficiency, whereas mutants expected to express neither ORF formed plaques with an efficiency less than 10(-6) that of wild-type virus. Thus, plaque-forming ability reflected late protein synthetic ability, suggesting that among these mutants late protein synthetic proficiency is the principle determinant of plaquing efficiency. PMID- 2911118 TI - Characterization of human immunodeficiency virus type 2 envelope glycoproteins: dimerization of the glycoprotein precursor during processing. AB - Four glycoproteins with apparent molecular weights of 300,000, 140,000, 125,000, and 36,000 (gp300, gp140, gp125, and gp36) were detectable in human immunodeficiency virus type 2 (HIV-2)-infected cells. gp125 and gp36 are the external and transmembrane components, respectively, of the envelope glycoproteins of HIV-2 mature virions. gp300 and gp140 are only detectable in virus-infected cells. They have identical isoelectric points, suggesting that gp300 might be a dimeric form of the immature precursor, gp140. The purified gp300 can be dissociated in a slightly acidic buffer to give rise to monomers of 140,000 molecular weight. Such dissociated monomers and the purified gp140 showed identical patterns of polypeptides after partial proteolysis with Staphylococcus aureus V8 protease. Pulse-chase experiments indicated that gp300 is formed after synthesis of gp140 and before the detection of the mature external envelope glycoprotein, gp125. These results were confirmed by using various inhibitors of glycosylation and inhibitors of trimming enzymes. Dimer formation of the envelope glycoprotein precursor was also observed in cells infected with simian immunodeficiency virus (SIV), a virus closely related to HIV-2. On the other hand, the envelope glycoprotein precursor of HIV-1 did not form a dimer during its processing. Therefore, dimer formation seems to be a specific property of HIV 2 and SIV envelope gene expression. Such transient dimerization of the glycoprotein precursor might be required for its efficient transport to the Golgi apparatus and for its processing. PMID- 2911119 TI - Infection of human peripheral blood mononuclear cells with a temperature sensitive mutant of measles virus. AB - A stable temperature-sensitive mutant of measles virus (MV ts38) was used to study the mechanism of virus-mediated immune suppression of peripheral blood mononuclear cells in vitro. Both unstimulated and phytohemagglutinin-stimulated cultures released infectious virus at 32 degrees C, whereas no virus was released at 37 degrees C, although both viral RNA and viral proteins were synthesized. However, the response of the lymphoid cells to phytohemagglutinin, concanavalin A, and herpes simplex virus antigen was decreased in the presence of MV ts38 at 37 degrees C. The viability of infected cells was not diminished, therefore excluding cell death as a reason for immunosuppression. Interleukin 2 did not play a role in the inhibitory effect of MV ts38. Antibodies to alpha interferon partially reversed the inhibitory effect of the virus infection on lymphocyte mitogenesis, thus implying that alpha interferon plays a role in the immunosuppression. Depletion experiments indicated that adherent cells play a greater role in the measles virus-induced immunosuppression than nonadherent cells. However, monocyte maturation to macrophages had no effect on the degree of immunosuppression. PMID- 2911120 TI - Fine structure mapping of five temperature-sensitive mutants in the 22- and 147 kilodalton subunits of vaccinia virus DNA-dependent RNA polymerase. AB - We have mapped the temperature-sensitive (ts) lesions of three mutants, ts51, ts53, and ts65, and two other mutants, ts7 and ts20, to regions on the vaccinia virus genome that encode the 147- and 22-kilodalton subunits of the viral DNA dependent RNA polymerase, respectively. Plasmid and bacteriophage clones from the HindIII J region and the region spanning the HindIII J-H junction were used in marker rescue experiments to map the mutations. Sequence analysis of the region encoding the 22-kilodalton subunit in the wild-type, ts7, and ts20 viruses revealed a single base change in the mutants compared with that in the wild-type virus. The identification of these RNA polymerase mutants provides us with tools to understand transcription and its regulation in vaccinia virus. PMID- 2911121 TI - Detailed phenotypic characterization of five temperature-sensitive mutants in the 22- and 147-kilodalton subunits of vaccinia virus DNA-dependent RNA polymerase. AB - We have carried out detailed phenotypic characterization of five temperature sensitive (ts) mutants of vaccinia virus, the ts lesions of which have previously been mapped to two different subunits of the viral RNA polymerase. We have also attempted to determine the mechanism of temperature sensitivity in these mutants. Phenotypic characterization of each of the mutants showed that at the nonpermissive temperature, all five mutants exhibited normal levels of early viral mRNA and protein synthesis, but for an extended period of time, all mutants accumulated normal levels of DNA in abnormally large pools in the cell cytoplasm; all mutants were defective in the synthesis of late viral mRNA and proteins and in viral morphogenesis. In an attempt to address the mechanism of temperature sensitivity in these mutants, we measured the effect of a temperature shift on the ability of the mutants to direct late viral protein synthesis. If infected cells were shifted down from a nonpermissive temperature late during infection, late protein synthesis was initiated after a lag period of 1 to 2 h. If infected cells were shifted up from a permissive temperature early during infection, late protein synthesis continued to be defective. If infected cells were shifted up to the nonpermissive temperature after late protein synthesis had commenced, late protein synthesis was maintained at the nonpermissive temperature at the level observed when the temperature was shifted up. We interpret these results to mean that once a functional RNA polymerase has been assembled at the permissive temperature during a mutant infection, it remains functional at the nonpermissive temperature, but that the ts mutants are defective in the assembly of a newly synthesized RNA polymerase at the nonpermissive temperature. This interpretation implies that the virion RNA polymerase is responsible for early viral transcription and that a newly synthesized RNA polymerase transcribes late viral genes. PMID- 2911122 TI - Characterization of bovine respiratory syncytial virus proteins and mRNAs and generation of cDNA clones to the viral mRNAs. AB - We have characterized the proteins and mRNAs of bovine respiratory syncytial (BRS) virus strain 391-2 and constructed cDNA clones corresponding to 9 of the 10 BRS virus mRNAs. The proteins of BRS virus-infected cells were compared with the proteins from human respiratory syncytial (HRS) virus-infected cells. Nine proteins specific to BRS virus-infected cells, corresponding to nine HRS virus proteins, were identified. Only a BRS virus polymerase protein remains to be identified. The BRS virus G glycoprotein showed major antigenic differences from the HRS virus G glycoprotein by immunoprecipitation and Western (immuno-) blot analysis, whereas the BRS virus F, N, M, and P proteins showed antigenic cross reactivity with their HRS virus counterparts. Analysis of RNAs from BRS virus infected cells showed virus-specific RNAs which had electrophoretic mobilities similar to those of mRNAs of HRS virus but which hybridized poorly or not at all with HRS virus-specific probes in Northern (RNA) blot analysis. To analyze the BRS virus RNAs further, cDNA clones to the BRS virus mRNAs were generated. Nine separate groups of clones were identified and shown to correspond to nine BRS virus mRNAs by Northern blot analysis. A 10th BRS virus large mRNA was identified by analogy with the HRS virus polymerase mRNA. These data show that like HRS virus, BRS virus has 10 genes coding for 10 mRNAs. PMID- 2911123 TI - Molecular genetic analysis of vaccinia virus DNA polymerase mutants. AB - To further our understanding of the structure and function of the vaccinia virus DNA polymerase, we have performed fine genetic analysis of three mutants with lesions in the polymerase gene. By performing marker rescue analysis with DNA fragments of decreasing size, each lesion was localized to within 500 base pairs of DNA. The relevant regions of the mutant alleles were then cloned and subjected to DNA sequence analysis, which allowed the assignment of a single nucleotide and amino acid change to each mutant. As well as providing structure-function correlations germane to an understanding of polymerase activity, these data have provided insights into the frequency and possible mechanisms of viral homologous recombination. PMID- 2911124 TI - Form-determining functions in Sindbis virus nucleocapsids: nucleosomelike organization of the nucleocapsid. AB - Purified intact Sindbis virus nucleocapsids were treated at different pH values or with various concentrations of divalent cations, cation chelators, salt, or formamide. The resulting structures were examined by velocity sedimentation, electron microscopy, and protein-protein cross-linking. Changes in each of the test conditions led to alterations in the sedimentation profile of treated nucleocapsids. Appropriate concentrations of formamide or divalent cations generated beaded strandlike structures similar in morphology to those generated from adenovirus cores and nucleosomes. The capsid protein and RNA remained associated with each other at NaCl concentrations less than or equal to 1 M or after treatment of the structures with alkaline pH up to and including pH 10.7. Protein and RNA were dissociated by salt concentrations of greater than 1 M, suggesting that the arginine-rich, amino-terminal portion of the capsid protein is responsible for binding the RNA. Protein-protein cross-linking also indicated that the capsid proteins remained associated in small aggregates under some of the conditions that caused dissociation of the nucleocapsid and suggested the presence of more than one type of protein-protein interaction in the nucleocapsids. Collectively, these data suggest that, like histones and adenovirus core proteins, the Sindbis virus capsid protein serves to package segments of the genome into nucleoprotein beads which are capable of interacting with each other to form the nucleocapsid structure. PMID- 2911125 TI - Liver-specific expression of hepatitis B virus is determined by the combined action of the core gene promoter and the enhancer. AB - The hepatitis B virus (HBV) enhancer and the core gene promoter regulate the expression of the core and polymerase genes, as well as of the 3.5-kilobase pregenomic RNA. RNA analysis and chloramphenicol acetyltransferase gene expression by plasmids carrying the HBV enhancer linked to the heterologous beta globin or simian virus 40 early promoter demonstrated that the HBV enhancer is 3- to 20-fold preferentially expressed in human liver cells. Core gene promoter activity was mapped to a 100-base-pair fragment which was shown to be sufficient for accurate initiation of transcription. The partial tissue specificity of this promoter was demonstrated by transient transfection into various cell lines with a plasmid containing the core gene promoter linked to the heterologous simian virus 40 enhancer. When the HBV core gene promoter was examined under the control of the HBV enhancer, there was high tissue specificity in that activity could be observed only in differentiated human liver cells. These results suggest that the strict tissue specificity of HBV gene expression is determined by the combinatorial action of these two elements. PMID- 2911127 TI - Transactivation of human immunodeficiency virus promoter by human herpesvirus 6. AB - Patients with acquired immunodeficiency syndrome (AIDS) are often infected with a number of other heterologous viruses in addition to the initial human immunodeficiency virus (HIV) infection, and these agents could act as potential reactivating agents of latent HIV. A new antigenically distinct herpesvirus, designated human herpesvirus 6 (HHV-6), has recently been isolated from patients with AIDS and has been shown to infect a number of different human cells, specifically human T cells, B cells, and glial cells. Since these are some of the same cells that harbor the AIDS virus, it is quite important to determine any interaction between this new herpesvirus and HIV. In this report, we demonstrate that HHV-6 can trans-activate the HIV promoter in human T-cell lines as measured by the expression of the bacterial gene chloramphenicol acetyltransferase. This indicates that stimulation of HIV gene expression by HHV-6 could play a role in HIV pathogenesis. PMID- 2911126 TI - Modulation of ppp(A2'p)nA-dependent RNase by a temperature-sensitive mutant of vaccinia virus. AB - Activation of the ppp(A2'p)nA (2-5A)-dependent RNase was investigated during the abortive infection of BSC40 cells by a temperature-sensitive mutant of vaccinia virus, ts22. At the nonpermissive temperature, ts22 has an abortive late phenotype. At the onset of late-viral-gene expression, viral mRNA is degraded and rRNA is cleaved into discrete fragments in the absence of prior interferon treatment (R. F. Pacha and R. C. Condit, J. Virol. 56:395-403, 1985). Concomitant with rRNA cleavage, an increase in 2-5A occurred late during infection. Discrete 18S- and 28S-rRNA degradation products from BSC40 cells infected with ts22 at the nonpermissive temperature comigrated in denaturing agarose gels with rRNA cleaved fragments produced by the activation of 2-5A-dependent RNase in uninfected cells transfected with exogenous 2-5A. An increase in 2-5A levels and a similar discrete and characteristic degradation of rRNA were observed in BSC40 cells infected with wild-type vaccinia virus in the presence of isatin-beta thiosemicarbazone. The results show that the ts22 lesion and the action of isatin beta-thiosemicarbazone may affect the same pathway, leading to the activation of latent 2-5A-dependent RNase and resulting in indiscriminate RNA degradation and inhibition of viral replication. PMID- 2911128 TI - Effect of Sindbis virus infection on induction of heat shock proteins in Aedes albopictus cells. AB - When Aedes albopictus cells (clone C7) were infected with Sindbis virus, the production of cytopathic effect CPE depended largely on the conditions under which the cells were cultured. We observed marked inhibition of cellular RNA and protein synthesis, as well as a loss of the ability to induce heat shock proteins, e.g., hsp70, under conditions which led to cytopathic effect. Infected cells in which heat shock proteins could no longer be induced contained much lower amounts of hsp70 mRNA after heat shock than did mock-infected cells which were similarly treated. It is suggested that this decreased level of hsp70 mRNA is due to a failure of these cells to synthesize hsp70 mRNA after heat shock. PMID- 2911129 TI - Plaque size phenotype as a selectable marker to generate vaccinia virus recombinants. AB - In this report, we provide a new method for selection of vaccinia virus recombinants expressing foreign genes. The method is based on the use of the gene encoding the viral 14,000-molecular-weight envelope protein that rescues the small-plaque-size phenotype of a vaccinia virus variant to large-plaque-size virus. Selection of recombinants is easily obtained after visual inspection of large viral plaques. PMID- 2911130 TI - Short-term and midterm results of an all-autogenous tissue policy for infrainguinal reconstruction. AB - Saphenous vein is the optimal conduit for infrainguinal vascular reconstruction. In instances in which this vein is unavailable or of "poor quality," reliance has been placed on a variety of prosthetic materials for bypass grafting. However, long-term patency with these prosthetic grafts has been disappointing. In January 1985 we instituted a policy of using exclusively autogenous tissue for infrainguinal arterial reconstruction. During the ensuing 3-year period, 203 patients underwent 266 arterial operations below the inguinal ligament, with a prosthetic graft used in only 11 instances (4%). No patient was denied surgery for limb salvage because of a lack of available autogenous vein. Thirty-three percent of procedures were performed for failure of prior revascularization and 73% for limb salvage. The 3-year cumulative primary patency rate for all autogenous procedures was 72%. Procedures were divided into those that used greater saphenous vein (patency 77%) vs autogenous alternatives such as bypass with arm vein or lesser saphenous vein, vein patch angioplasty, and endarterectomy (patency 64%). The operative mortality rate was 1.4% and the 3 year limb salvage rate was 89%. Autogenous infrainguinal reconstruction can be performed in almost every instance with acceptable results, suggesting that the need for prosthetic bypass grafts in the lower extremity is less than has been previously reported. PMID- 2911131 TI - Internal carotid artery occlusion: effect of contralateral flow reduction in inducing symptoms. AB - Cerebral ischemic attacks ipsilateral to an occluded internal carotid artery (ICA) continue in more than 16% of patients. With common carotid artery compression on the side of ICA occlusion in 53 patients, the mean (+/- SEM) ophthalmic systolic pressure/brachial systolic pressure (OSP/BSP) ratio fell from 0.58 +/- 0.013 to 0.42 +/- 0.020 (p less than 0.001), without any cerebral ischemic symptoms. Compression of the contralateral patent common carotid artery resulted in the ophthalmic systolic pressure/brachial systolic pressure ratio dropping from 0.67 +/- 0.012 to 0.29 +/- 0.017 (p less than 0.001) on the patient side and from 0.58 +/- 0.013 to 0.48 +/- 0.018 (p less than 0.001). Twenty-six of 53 patients (49%) developed ischemic symptoms in response to compression of the remaining patent ICA system. In contrast, only 8 of 122 patients (6.5%) without ICA occlusion developed any symptoms of cerebral dysfunction (p less than 0.001). This study suggests embolic events rather than flow reduction may be of greater importance in the production of new symptoms and that contralateral flow is critical to normal cerebral function in half the population with ICA occlusion. PMID- 2911132 TI - Results of supraceliac aortic clamping in the difficult elective resection of infrarenal abdominal aortic aneurysm. AB - We have used clamping of the aorta above the celiac axis (SC) in 30 of 431 elective resections of infrainguinal abdominal aortic aneurysms (AAA) during the past five years as an alternative to a difficult aortic cuff dissection. The results of SC clamping in these 30 patients are compared with the results of 379 routine aneurysm resections with infrarenal (IR) clamping and 22 additional aneurysm resections where the clamp was placed immediately above the renal arteries. These difficult cuff dissections occurred in 12 patients with inflammatory AAA, in 11 patients with juxtarenal AAA, and in seven patients with recurrent or noninfected false AAA of the proximal cuff. Patients with ruptured or suprarenal aneurysms and those undergoing combined operation for a visceral ischemic syndrome and an aneurysm were excluded from this study. Patients with SC clamping had similar operative mortality rates, comparable renal function, and frequency of cardiac events as patients with IR clamping. Blood loss was slightly higher in the SC group (p = 0.07) and serum aspartate amino transferase (AST) levels were three times higher than in the IR group; however, this was of no clinical significance. In contrast, those 22 patients whose aortas were clamped immediately above the renal arteries (AR) had higher perioperative mortality rates (2% IR, 3% SC vs 32% AR) and a higher incidence of kidney failure requiring dialysis (1% IR, 3% SC vs 23% AR). The mean values of serum creatinine and blood urea nitrogen were also significantly higher in the AR group when compared with both the IR and the SC groups (IR: 25 and 1.5 mg/dl, respectively; SC: 27 and 1.8 mg/dl; AR: 41 and 3.5 mg/dl). The single most important risk factor accounting for the differences between clamping above the celiac artery and clamping above the renal arteries was the presence of atherosclerotic debris in the nonaneurysmal, juxtarenal aortic segment. Clamping the aorta with juxtarenal atherosclerosis caused either atheroembolization to kidneys, legs, and intestine or injury to the aorta, renal arteries, or both; it was the cause of morbidity in all five cases of kidney failure requiring dialysis and accounted for all seven of the deaths in the AR group. SC clamping does not add risk to the patient undergoing resection of an infrarenal AAA and is the preferred method of achieving proximal control of the infrarenal aorta when a a hazardous cuff dissection is likely.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2911133 TI - Effects of thoracic aortic occlusion and cerebrospinal fluid drainage on regional spinal cord blood flow in dogs: correlation with neurologic outcome. AB - We studied the effect of thoracic aortic occlusion and cerebrospinal fluid (CSF) drainage on regional spinal cord blood flow and its correlation with neurologic outcome. Using isotope-tagged microspheres, we determined blood flow to the gray and white matter of five regions of the spinal cord in dogs: group I (control), group II (cross-clamp only), group III (cross-clamp plus CSF drainage). At 60 minutes after thoracic aortic occlusion in group II, median gray matter blood flow (GMBF) in the lower thoracic and lumbar cord decreased from 23.1 and 27.0 ml/100 gm/min at baseline to 4.0 and 2.5 ml/100 gm/min, respectively. The addition of CSF drainage improved GMBF during aortic cross-clamping in the lower thoracic and lumbar cord to 11.3 (p less than 0.05) and 15.1 ml/100 gm/min (p less than 0.03), respectively. After removal of the aortic cross-clamp, median blood flow more than tripled from baseline blood flow in group II, whereas CSF drainage prevented significant reperfusion hyperemia. Both low GMBF during cross clamping and reperfusion hyperemia were associated with a worse neurologic outcome. In group II, no dog was neurologically normal, and more than 60% of the dogs had spastic paraplegia. In contrast, almost 60% of dogs in group III were normal, and none had spastic paraplegia (p less than 0.001). We conclude that CSF drainage in dogs during thoracic aortic occlusion maintained spinal cord perfusion above critical levels, diminished reperfusion hyperemia, and improved neurologic outcome. PMID- 2911134 TI - Abnormalities of lymphatic drainage in lower extremities: a lymphoscintigraphic study. AB - Chronic lower-leg edema in patients with venous disorders was studied by means of lymphoscintigraphy. Lymphatic patterns of flow were evaluated prospectively in 26 patients with technetium 99m antimony trisulfide colloid injected subcutaneously in the interdigital web spaces on the feet. Most patients in this study had postphlebitic syndrome, and all of these patients had abnormal lymphoscintigraphic flow patterns. Nine had evidence of lymphatic obstruction, and one had an enhanced flow pattern. Three patients had veins used for distal arterial bypass, and all these veins showed decreased lymphatic flow. Two patients with Klippel-Trenaunay syndrome (congenital varicose veins associated with limb elongation, a capillary nevus, and an abnormal deep venous system) had obstruction to lymphatic flow, and two others had normal and enhanced patterns. Normal studies were seen in four of five patients who had veins used for coronary artery bypass grafting. The finding of decreased lymphatic flow in patients appears to be the result of the length of time from an episode of deep venous thrombosis, the occurrence and number of episodes of cellulitis and lymphangitis, and mobilization of the vein for use in distal arterial bypass surgery. This study shows that the edema attributed previously to primary venous disorders may have a significant lymphatic component. The degree of lymphatic obstruction can be determined by lymphoscintigraphy with technetium-labeled antimony trisulfide colloid. PMID- 2911135 TI - Fibrinolytic treatment of residual thrombus after catheter embolectomy for severe lower limb ischemia. AB - Intraoperative intraarterial fibrinolytic therapy (IIFT) was employed in 28 patients with acute limb ischemia. In 17 patients, significant residual calf thrombus was demonstrated by completion arteriography after standard balloon catheter thromboembolectomy, whereas in 11, pretreatment arteriography was not obtained. With the patient systemically heparinized, a bolus of fibrinolytic agent was instilled into the distal vessels below an inflow occlusion clamp. Among the 17 patients under angiographic control, arteriography was repeated after 30 minutes and a second bolus was injected if significant residual thrombus was still present. Successful lysis was achieved in 88% of these 17 limbs and streptokinase (SK) and urokinase (UK) were equally effective. The dosage of SK varied between 50,000 and 150,000 units (seven patients) and of UK between 35,000 and 150,000 units (21 patients). Serum fibrinogen levels declined significantly after IIFT (t test; p less than 0.05), but the average level remained within the normal range. Major bleeding developed in two patients, both of whom received SK and underwent a concomitant major abdominal vascular procedure, with a severe fall in fibrinogen values to 10 and 17 mg/dl. A minor groin hematoma occurred in one patient treated with UK. There was a significant difference in the incidence of bleeding between SK (2/7) and UK (1/21) (chi 2; p less than 0.05). Compartment syndrome developed in six limbs (21%). Amputation was required in two patients (7%). There was no correlation between prolongation of ischemia time as a result of IIFT and the incidence of compartment syndrome.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2911136 TI - Intraarterial urokinase increases skeletal muscle viability after acute ischemia. AB - Administration of intraarterial fibrinolytic agents has been recommended after balloon catheter thrombectomy to reduce retained thrombus and to improve the patency of collateral vasculature. However, the potential for improvement in the viability of skeletal muscle after ischemia as a result of this therapy has not been evaluated. We investigated the effect of intraarterial urokinase (UK) on the salvage of ischemic skeletal muscle in a bilateral, in vivo, isolated gracilis muscle model. In six anesthetized dogs each gracilis muscle was subjected to 5 hours of ischemia by temporary occlusion of the gracilis artery. Before reperfusion, the experimental muscle received an intraarterial infusion of UK (30,000 units) whereas the control muscle received saline solution. Each muscle was then reperfused for 90 minutes. Triphenyltetrazolium chloride staining demonstrated infarction of 20.2% +/- 8.1% in control muscles compared with 8.6% +/- 6.2% in UK-infused muscles (p less than 0.01). Control muscles gained significantly more weight from edema (33.6 +/- 5.9 gm) than UK-infused muscles (18.2 +/- 4.1 gm; p less than 0.05). Coagulation studies confirmed that an isolated fibrinolytic effect occurred on the experimental side. These studies suggest that intraarterial UK may be a useful adjunctive therapy after revascularization of the acutely ischemic limb and that further clinical trials are recommended. PMID- 2911137 TI - Jugular-axillary vein bypass for salvage of arteriovenous access. AB - Stenosis or occlusion of the subclavian vein can cause incapacitating upper extremity swelling and venous hypertension in the patient with an arteriovenous (AV) access. A case of subclavian vein occlusion is reported that was treated with internal jugular-axillary vein bypass. This procedure resulted in salvage of the access and rapid resolution of the associated upper extremity swelling. It was concluded that jugular-axillary vein bypass should be considered in patients who have massive upper extremity edema resulting from a functioning AV access and ipsilateral subclavian vein occlusion. Patients undergoing creation of an AV access who have had previous temporary subclavian catheters or previous early failure of an AV access should have phlebography before surgery. PMID- 2911138 TI - Abdominal aortic and multiple iliac aneurysms associated with crossed-fused ectopia of the kidney: a case report and review. AB - We report the first case of an infrarenal abdominal aortic aneurysm associated with crossed-fused ectopia of the kidney. This is the second most common fusion defect of the kidney with an incidence in the general population of 1 in 1000. The different types of crossed renal ectopia with and without fusion are described. The renal artery anomalies associated with crossed renal ectopia are emphasized. Abdominal ultrasonography or CT scanning must be used to uncover renal anomalies before surgery so that a selective preoperative aortogram can be obtained to determine the location of the arterial supply to the kidneys. PMID- 2911139 TI - Direct noninvasive monitoring of spinal cord motor function during thoracic aortic occlusion. PMID- 2911140 TI - Renal artery aneurysm: selective treatment for hypertension and prevention of rupture. AB - Thirty-nine patients with renal artery aneurysm (RAA) were seen over a period of 15 years. Among 20 women and 19 men, 31 were found to have solitary aneurysms, and eight had multiple RAA. Thirty-three patients had diastolic hypertension; nine of them proved to be of renovascular origin. Of the 18 patients who underwent RAA resection, 13 had reconstruction for treatment of hypertension, three had a solitary functional kidney, one had recurrent flank pain, and one had resection for prevention of rupture in a woman of childbearing age. Six of the 18 patients had aneurysmorrhaphy with primary repair or patching, seven had a resection with an aortorenal bypass, and five patients had six ex vivo renal reconstructions with multiple anastomoses. Nephrectomy was performed in two patients with RAA rupture at the time of childbirth and in one patient with hypertension and RAA in a poorly functioning kidney. Reconstructive procedures for documented renovascular hypertension in seven patients resulted in improvement in all cases. Blood pressure improved in only six of 10 patients operated on with hypertension and no lateralization of renovascular studies. Eighteen patients were observed for one to 16 years without surgery, and none experienced rupture. Resection of RAA is indicated to treat patients with renovascular hypertension, patients with hypertension and a solitary functional kidney, and selected patients with severe hypertension and to prevent rupture in women who may become pregnant. Other patients with asymptomatic RAA can be safely observed clinically without serial arteriograms and without fear of rupture.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2911141 TI - Does compliance mismatch alone cause neointimal hyperplasia? AB - To define the relationship between compliance mismatch and the development of neointimal hyperplasia, one 3 cm segment of common iliac artery was externally banded in seven dogs, thereby fixing the arterial diameter at end diastole. To quantify compliance, end-diastole diameter and its change with pulse pressure were measured by induction angiometry. This technique uses intravascular soft trifilar wire probes introduced through distally placed polytetrafluoroethylene sidearms. Compliance was checked in the banded and contralateral undissected unbanded control iliac arteries at 3 and 6 months, at which times the vessels were fixed by perfusion, excised, and examined histologically. Sustained (6 month) compliance mismatch was successfully induced within the banded segments (p less than 0.0001), and no compliance mismatch was seen in the control segments (p = 0.357). The intima of all banded vessels was virtually indistinguishable from that in controls grossly and histologically. Mild focal intimal thickening, less than 3 cell layers thick involving less than 5% of the vessel circumference, was typically seen in both banded and control vessels (range 6.57 +/- 6.80 micron to 38.86 +/- 57.16 micron). In marked contrast, at the sites of the polytetrafluoroethylene-to-femoral artery anastomosis, near-occlusive neointimal hyperplasia (1714 +/- 415.47 micron) was seen in all animals. Residual lumen area in the banded and control vessels was only minimally abnormal (range 98.65% +/- 2.18% to 99.96% +/- 0.08%). These data indicate that compliance mismatch alone is an insufficient stimulus for the development of neointimal hyperplasia in the canine model. PMID- 2911142 TI - Renovascular hypertension in children. Surgical repair with special reference to the use of reinforced vein grafts. AB - Surgical correction of renovascular hypertension in children is especially challenging because there is high incidence of bilateral renal artery lesions and stenosis of the abdominal aorta. Seventeen patients with severe hypertension, whose ages ranged from 2 to 16 years (mean 10.2 years), had surgical repair of these lesions from 1974 to 1987. Twenty-nine renal artery lesions were repaired. Twelve (71%) were bilateral, five (29%) were unilateral, and eight patients (47%) had abdominal aortic lesions (midaortic stenosis). Twenty-eight saphenous vein grafts and one splenorenal graft were used to bypass the renal artery lesions. The midaortic lesions were bypassed with Dacron grafts from the superceliac aorta to the aortic bifurcation. No operative deaths occurred. Nineteen of the 28 vein grafts were reinforced with a 6 mm diameter tubular Dacron mesh to prevent aneurysmal degeneration seen in three of nine unsupported vein grafts. Follow-up arteriograms were available in 15 patients up to 11 years after operation (mean 5.0 years). There has been no aneurysmal dilatation in the 19 mesh-supported grafts. The ratio of vein graft diameter to the diameter of the native aorta was 1.25 +/- 0.38 (+/- standard deviation) in unsupported grafts and 0.65 +/- 0.09 in mesh-supported grafts, representing a 92% increased diameter in the unsupported grafts. Three vein grafts (10.3%) required percutaneous transluminal angioplasty for late postoperative vein graft stenoses, but no stenotic lesions have developed at the aortic suture lines. One graft occluded 7 years postoperatively after replacement of an aneurysmal vein graft, and one early postoperative graft occlusion occurred, for a graft failure rate of 7%. Seventy-six percent of patients (13 of 17) are normotensive without medication, and 24% (4 of 17) are considered improved with hypertension controlled with a lower dose of medication. Our results attest to the safety and efficacy of this complicated surgery. Saphenous veins, supported by external Dacron mesh, appear to be a suitable graft material for renal reconstruction in this population. PMID- 2911144 TI - The risk of stroke with occlusion of the internal carotid artery. AB - Reports of all cervicocephalic arteriograms (n = 1836) performed at one institution during a 10-year period were reviewed and the patients were classified into three groups according to the indication for arteriography. Group I included all patients with symptoms or findings compatible with occlusive disease of the carotid or vertebral artery (n = 806). Group II included patients with cerebrovascular symptoms unrelated to carotid or vertebral disease (e.g., patients with subarachnoid hemorrhage) (n = 367). Group III consisted of patients with no evidence of cerebrovascular disease (e.g., patients with primary and metastatic brain tumors) (n = 663). One hundred ten atherosclerotic occlusions of the internal carotid artery (ICA) were found in 106 patients in group I. Fifty one percent of these patients had a history of stroke before arteriography, 24% had transient ischemic attacks (TIAs) or amaurosis fugax (AF), and 12% had nonhemispheric symptoms. Only 13% (1.7% of group I patients) were without symptoms. Ninety-one percent of the strokes and 75% of the TIAs or AF were ipsilateral to the ICA occlusion. Seventy-six percent of patients with stroke and 80% with ipsilateral TIAs or AF vs only 29% of patients without symptoms had contralateral stenosis of 60% diameter reduction or greater (p less than 0.003). No occlusions of the ICA occurred in groups II or III. Three hundred forty-six patients in groups II and III were more than 60 years of age. Assuming either Poisson or binomial distributions, the incidence of silent ICA occlusion in the population at large older than 60 years was estimated at less than 1% (p less than 0.03). PMID- 2911143 TI - Carotid endarterectomy in the elderly population: a statewide experience. AB - The practice of carotid endarterectomy (CEA) was examined in all Medicare patients undergoing operation in the state of Kentucky during 1983 and during the first 6 months of 1984. CEA was performed 738 times on 705 patients in 1983 by 98 surgeons in 41 hospitals. The average age of patients was 71 years, and only 15% had no symptoms of carotid disease. The stroke rate was 3.7%, and the combined stroke and mortality rate was 5.7%. In a follow-up period in 1984, the combined stroke and mortality rate was 4.3%. Patients who showed no symptoms of carotid disease had a combined stroke and mortality rate of 2.8%. Surgeons performing fewer than three CEAs per year had a tendency toward a higher complication rate than had surgeons performing more than 12 CEAs a year. Most stroke complications appeared as isolated events and did not seem to represent a practice pattern based on our follow-up into 1984. PMID- 2911145 TI - Particle size distribution of lipoproteins from human atherosclerotic plaque: a preliminary report. AB - It is commonly believed that low-density lipoproteins (LDLs) carry cholesterol into the artery wall. In addition, some epidemiologic studies have suggested that triglyceride-rich lipoproteins, such as very-low-density lipoproteins (VLDLs), may be much less important than LDLs in atherogenesis. To determine if VLDLs or their metabolic remnants could have a direct role in the formation of atherosclerotic plaque, we examined lipoproteins isolated from endarterectomy specimens. Atherosclerotic plaque was obtained from eight subjects who underwent aortoiliac endarterectomy (4), aortic aneurysm repair (2), or visceral/renal endarterectomy (2). Plaques were washed extensively, minced, and incubated with a buffered saline solution. Lipoproteins were recovered from this solution via a selected-immunoaffinity column by means of a polyclonal antibody to human LDL (apolipoprotein B-100). Particle sizing from electron photomicrographs of negatively stained specimens indicated that 8% of the lipoprotein particles were the size of plasma VLDL (350 to 800 nm). Thirty-six percent were the size of plasma VLDL remnant particles (250 to 350 nm), and 56% were consistent in size with plasma LDL (175 to 250 nm). We conclude that VLDL- and VLDL remnant-sized particles appear to comprise a significant percentage of the lipoproteins found in human atherosclerotic plaque and could have a direct role in the atherosclerotic process. PMID- 2911146 TI - Spontaneous lysis of deep venous thrombi: rate and outcome. AB - Ultrasonic duplex scanning was used to study the rates at which lysis of thrombi, valvular incompetence, and symptoms of the postthrombotic syndrome (edema) developed in 21 patients after deep venous thrombosis (DVT). Lysis of thrombi occurred rapidly in most patients. In 11 of 21 patients (53%), recanalization occurred in all segments by 90 days after presentation. In four patients, extension of the initial DVT occurred between 30 and 180 days, despite treatment with warfarin. Valvular incompetence developed in 13 patients during the study period. The number of patent venous segments with incompetent valves increased from the initial presentation to 180 days, at which time 25% of patent segments contained incompetent valves. Valvular incompetence developed in previously thrombosed segments that were initially competent after recanalization and in segments not previously thrombosed. This suggested that although incompetence may occur as a result of a direct effect of the thrombus on the valve, other mechanisms must also be involved. Patients with edema early after DVT (from 7 to 30 days) were more likely to have residual occlusion than valvular incompetence. The late development of edema (from 90 to 270 days) was more closely correlated with valvular incompetence. PMID- 2911147 TI - Normal endothelial function and decreased vasoreactivity of experimental arterial grafts. AB - During autogenous vascular grafting endothelial cell damage inevitably occurs. In this study we examined the functional and morphologic integrity of experimental arterial grafts. The right external iliac artery was grafted into the right carotid artery of 12 male New Zealand white rabbits. The left external iliac artery was used as the control artery. Four weeks after surgery, isometric tension studies were performed on rings of control artery and arterial graft. Control arteries and arterial grafts precontracted with norepinephrine demonstrated endothelium-dependent relaxation of 28.3% +/- 5.6% and 16.1% +/- 1.7%, respectively, in response to acetylcholine (5 x 10(-6) mol/L). Both control arteries and arterial grafts contracted in response to norepinephrine, histamine, and serotonin. The median effective dose (ED50) of norepinephrine was 4.1 +/- 1.3 x 10(-7) mol/L for control arteries and 62.1 +/- 17.9 x 10(-7) mol/L for arterial grafts (p less than 0.005). Similarly, arterial grafts were less sensitive to histamine; the ED50 of histamine for control arteries was 4.6 +/- 1.3 x 10(-7) mol/L and 51.4 +/- 13.0 x -7 mol/L for arterial grafts (p less than 0.005). In contrast, reactivity to serotonin was unaltered. The ED50 was 4.1 +/- 1.3 x 10( 7) mol/L for control arteries and 4.5 +/- 1.3 x 10(-7) mol/L for arterial grafts. Scanning and transmission electron microscopy revealed a largely intact endothelial surface. These data are markedly different from our previous findings with vein grafts in which serotonin supersensitivity was associated with an absence of endothelium-mediated relaxation to acetylcholine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2911149 TI - Once again, mice come to research's rescue, this time as infection models in AIDS studies. PMID- 2911148 TI - Epidemiologists aim at new target: health risk of handgun proliferation. PMID- 2911150 TI - Artificial lenses under development to focus on near, as well as more distant, objects. PMID- 2911151 TI - Pregnancy Dx? Rx may now include condoms. PMID- 2911152 TI - Leads from the MMWR. Death investigation--United States, 1987. PMID- 2911153 TI - Leads from the MMWR. Impact of homicide on years of potential life lost in Michigan's black population. PMID- 2911154 TI - Leads from the MMWR. Update: influenza activity--worldwide. PMID- 2911155 TI - Chronic fatigue. PMID- 2911156 TI - Bondage, dominance, irrigation, and Aeromonas hydrophila: California dreamin'. PMID- 2911157 TI - Decisions to limit care. PMID- 2911158 TI - Fish oil. PMID- 2911159 TI - Fish oil and SI units. PMID- 2911161 TI - The quality of care is unmeasurable: an equation, a paralogism, a paraphrasis, a quackery ... and a reply. PMID- 2911160 TI - Spanish medicine. PMID- 2911162 TI - What happened? You can tell me: I'm a provider. PMID- 2911163 TI - Dorsal penile nerve block for circumcision. PMID- 2911164 TI - Glaucoma presenting as hiccups. PMID- 2911165 TI - Methemoglobinemia following neonatal circumcision. PMID- 2911166 TI - Invasive pneumococcal disease in an Alaska native population, 1980 through 1986. AB - From 1980 through 1986, one hundred fourteen Alaska Native patients from the Yukon-Kuskokwim Delta had community-acquired invasive pneumococcal disease confirmed by isolates of Streptococcus pneumoniae from normally sterile body sites. The annual bacteremia rates per 100,000 persons were 105 cases for all ages, 1195 cases for infants under 2 years of age, and 130 cases for adults over 59 years of age. These were six to 34 times higher than rates reported for other US populations. The most common underlying conditions in infants diagnosed before 24 months of age were previously diagnosed anemia and pneumonia, while alcoholism and anemia were most common in adults. The case-fatality rate for infants under 2 years of age was 3.2%, and the case-fatality rate for adults over 59 years of age was 30%. Serotyping of more than half the isolates identified 96% of these isolates to be present in the currently available pneumococcal polysaccharide vaccine. The pneumococcal disease rates reported herein are likely to be underestimates since most diseases that occur in this region are treated at the village level without laboratory confirmation. PMID- 2911167 TI - Risk of developing AIDS in HIV-infected cohorts of hemophilic and homosexual men. AB - The latency period and/or incidence of the acquired immunodeficiency syndrome (AIDS) may differ in persons infected with the human immunodeficiency virus by different routes or having different "cofactors." We compared 79 hemophilic men in Pennsylvania and 117 homosexual and bisexual men in California, all having known dates of infection and long postinfection observation periods, to examine these hypotheses. By 1987, twenty-one percent of the hemophilic and 27% of the homosexual men had developed AIDS. However, seroconversion patterns differed for the two groups, and when this was taken into account, the conditional odds ratio for AIDS was 1.20. Kaplan-Meier survival analysis showed no significant difference in the cumulative proportion with AIDS, from time of infection. These results are limited by the small size and geographically localized nature of our study populations, but they suggest that currently the relative length of human immunodeficiency virus infection is of primary importance in comparing disease outcome for different populations. PMID- 2911168 TI - Pregnancy and travel. AB - The special problems of travel during pregnancy have become clinically important as more women are traveling to remote places for business or recreation. Optimal maintenance of fetal and maternal health under these circumstances entails specific considerations for which data, unfortunately, remain incomplete. Nevertheless, questions regarding immunizations, antimalarials, therapy for traveler's diarrhea, and even the risks of high altitude or vigorous exercise for the pregnant woman may be examined clinically. With a few important exceptions, sufficient information is available to ensure relatively safe travel in pregnancy provided precautions are taken and preparations are made. PMID- 2911169 TI - Incidence of acute mountain sickness at intermediate altitude. AB - The incidence of acute mountain sickness was determined by questionnaire in 454 individuals who attended week-long continuing medical education programs at ski resorts in the Rocky Mountains with base elevations of about 2000 m. As a control group, 96 individuals who attended continuing medical education programs at sea level in San Francisco completed similar questionnaires. Study subjects were classified as having acute mountain sickness when they reported three or more of the five possible cardinal symptoms: headache, insomnia, dyspnea, anorexia, and fatigue. Only symptoms with an intensity of at least grade 2 (moderate) out of 5 were analyzed. Acute mountain sickness-like symptoms occurred in 25% of subjects at 2000 m compared with 5% of subjects at sea level. The incidence of acute mountain sickness at 2000 m was greatest among subjects who had come from lower altitudes. Half of the subjects with symptoms took medication. The duration of symptoms was short, with 90% of all symptoms that were reported occurring in the first 72 hours. Acute mountain sickness is common at intermediate altitudes, and it is frequently severe enough to prompt self-medication. PMID- 2911170 TI - Effects of dexamethasone on the incidence of acute mountain sickness at two intermediate altitudes. AB - To test the value of dexamethasone acetate for ameliorating acute mountain sickness (AMS), we conducted a double-blind, randomized study that compared the effects of 4 mg of dexamethasone acetate or a placebo (given every six hours for six doses beginning at the time of exposure) at 2700 and 2050 m. Study subjects, who were recruited from health professionals who attended continuing medical education programs at ski resorts in the Rocky Mountains, were classified as having AMS when they reported three or more of the five usual symptoms (headache, insomnia, dyspnea, anorexia, and/or fatigue) on a single day. All symptoms with an intensity of at least grade 2 (moderate) out of 5 were analyzed. At 2700 m, there was a 50% decrease in the mean AMS symptom score in the dexamethasone group (0.94 +/- 1.11 vs 1.84 +/- 1.44 [mean +/- SD]) and the incidence of AMS was 20% of that in the control group (3/38 vs 14/35). At 2050 m, there was no difference between dexamethasone and a placebo in the mean AMS symptom score (1.52 +/- 1.50 vs 1.24 +/- 1.33) and the incidence of AMS (5/25 vs 4/25). Dexamethasone ameliorates the usual symptoms of AMS at 2700 m but not at 2050 m. PMID- 2911171 TI - Innovations in monoclonal antibody tumor targeting. Diagnostic and therapeutic implications. PMID- 2911172 TI - Supporting the health care team in caring for patients with AIDS. PMID- 2911173 TI - The international congress on peer review in biomedical publication. PMID- 2911174 TI - The JAMA Journal Club. PMID- 2911175 TI - A piece of my mind. Belinda, asleep without dreams. PMID- 2911176 TI - Twenty years of medical advances. PMID- 2911177 TI - Animal rights activists distort issues. PMID- 2911178 TI - Animals in research: many alternatives exist. PMID- 2911179 TI - United States and Canadian Academy of Pathology. (United States-Canadian Division of the International Academy of Pathology). Annual meeting. San Francisco, March 5-10, 1989. Abstracts. PMID- 2911180 TI - Society for Pediatric Pathology. Annual meeting. San Francisco, CS, March 4-6, 1989. Abstracts. PMID- 2911181 TI - Type X collagen in avian tibial dyschondroplasia. AB - Tibial dyschondroplasia (TD) is an abnormality of the growth plate of growing chicks characterized by the presence of a mass of nonvascularized, nonmineralized cartilage. To determine if the morphologic changes observed in TD lesions are accompanied by biochemical abnormalities of the cartilage matrix, we performed quantitative and qualitative analyses of collagen in affected cartilage, placing special emphasis on the study of type X collagen, a recently described molecular species that may play a role in endochondral ossification. Collagen from TD lesions of 25-day-old chicks and from growth plate cartilage of normal age matched chickens and from hypertrophic cones of 1-day-old chicks was sequentially extracted, purified and characterized. No differences were noted in total collagen content and extractibility between these tissues. Determination of the relative amounts of the various collagens extracted showed that type X collagen in the TD lesion was markedly reduced since it was less than half of that found in pure hypertrophic cartilage. These results are consistent with previous morphologic and biochemical studies which suggest a failure of the chondrocytes to fully achieve maturation and hypertrophy. No differences were demonstrated in the CNBr peptide patterns or amino acid composition of type X collagen from normal or TD and hypertrophic cartilages, suggesting that the low content of type X collagen in TD lesion was due to alterations in type X collagen metabolism rather than to structural abnormalities in these molecules. PMID- 2911182 TI - X-radiation-induced differentiation of xenotransplanted human undifferentiated rhabdomyosarcoma. AB - A serially xenotransplantable strain of undifferentiated embryonal rhabdomyosarcoma originating from the nasal cavity of a 42-year-old woman has been established in our laboratory. After radiotherapy for the tumor donor, distinct rhabdomyoblastic differentiation of the undifferentiated sarcoma cells appeared in the primary lesion, and it is a reasonable assumption that X irradiation has a certain potentiality to induce morphologic differentiation of tumor cells. To study this possibility, tissue fragments of undifferentiated embryonal rhabdomyosarcoma that had grown to more than 10 mm after being transplanted to nude mice were selectively irradiated in situ. The degree of rhabdomyoblastic differentiation according to radiation dose was evaluated by light and electron microscopy and by immunostainability for myoglobin, creatine phosphokinase-MM, and desmin. Distinct morphologic differentiation of undifferentiated sarcoma cells could be induced by repeated X-irradiations at several-week intervals. PMID- 2911183 TI - Leukemic cell-endothelial cell interactions in leukemic cell dissemination. AB - In some human and experimental leukemias and lymphomas, the pattern of metastasis can be correlated with the homing sites of the normal progenitor cells. In vitro binding assays and homing experiments with murine lymphoma cell lines suggest that the nonrandom distribution of metastasis could be determined by specificity of cell-endothelium binding. A single subcutaneous inoculum of L2C cells in strain II guinea pigs resulted in a predictable stereotyped pattern of metastasis. Leukemic cell infiltrates were mainly observed around veins at specific locations in each organ: in brain, the most superficial leptomeningeal veins; in liver, veins of the portal triads; in lung, peribronchial veins; in kidney, veins of the renal columns; in adrenal gland, capsular veins and veins of the medulla. Those vessels also showed intense leukemic cell binding and diapedesis. This would suggest that the leukemic infiltrates were the result of transvenular traffic in these regions. Because leukemic cells were both in the intra- and extravascular compartments, the direction of the cell migration could not be determined. When L2C cells were injected into the right auricle of normal guinea pigs, leukemic cell binding occurred almost exclusively in veins located in areas of metastasis predilection. In addition, extravasation by diapedesis occurred in high endothelial venules in lymphoid organs, peribronchial veins and veins in the portal triads. Neither leukemic cell binding nor diapedesis occurred at the sinusoidal or capillary levels; extravasation in these vessels results from intravascular proliferation and secondary damage of the vessel wall, not by diapedesis. Our data suggest the existence in several organs of the guinea pig of a widely distributed, yet discrete, system of venular endothelial cells specialized in the traffic of leukemic cells. PMID- 2911184 TI - Progression to cancer in Barrett's esophagus is associated with genomic instability. AB - Barrett's esophagus is a condition in which metaplastic columnar epithelium replaces squamous esophageal epithelium as a consequence of chronic gastroesophageal reflux. Patients with this condition are at increased risk for the development of adenocarcinoma. To better understand the progression to adenocarcinoma in this disease, we studied abnormalities in DNA content of epithelial cells in Barrett's esophagus. Using flow cytometry, we examined the spatial distribution of abnormal nuclear DNA contents (aneuploidy) in the esophagi of 14 patients with Barrett's adenocarcinoma. Multiple (2 to 14) populations of aneuploid cells were seen in 12 of the 14 cases. Some early carcinomas appeared to be associated with a single aneuploid population of cells. Surrounding dysplastic epithelium often contained multiple, different overlapping aneuploid populations. These data suggest that neoplastic progression in Barret's esophagus is associated with a process of genomic instability which leads to evolution of multiple aneuploid populations, with the ultimate development of a clone of cells capable of malignant invasion. Thus, detection of multiple aneuploid populations of cells in Barrett's esophagus may indicate a high risk of cancer. Barrett's esophagus provides a unique and readily accessible model for the study of neoplastic progression in human epithelial malignancy. PMID- 2911185 TI - Asynergy of right ventricular wall motion in man. AB - Canine studies have shown a correlation between instantaneous segmental lengths in the right ventricular free wall and chamber volume, pressure, and stroke work. To determine whether such correlations exist in intact man, we studied the temporal relationships between chord dynamics in various regions of the right ventricle in 21 heart transplant recipients with apparently normal right ventricular function. Patients were examined by biplane radiography while performing various maneuvers (e.g., Valsalva maneuver). Computer-aided analysis of biplane radiograms of five surgically inserted radiopaque tantalum right ventricular myocardial markers was used to calculate interpoint chord lengths at 33 msec sampling intervals. Two patterns of right ventricular chord asynergy were defined: (1) An akinetic chord had an amplitude of less than 2.0 mm during the course of at least one beat; (2) an out-of-phase chord was more than a quarter period out of phase from the average curve (derived from all concurrently measured marker pairs during each maneuver) for at least one beat. Considering all chords (n = 978), 60 chords (6.1%) were akinetic and nine chords (0.9%) were out of phase. Excluding the outflow tract markers (n = 581), 33 chords (5.7%) were akinetic and five chords (0.9%) showed out-of-phase movement. During some maneuver, at least one akinetic chord occurred in 57% of patients and out-of phase chords in 33% of patients. Most right ventricular regions were implicated in asynergic motion, including the right ventricular free wall, acute margin, and outflow tract. The frequency and distribution of asynergy in right ventricular chord dynamics observed in this study suggests that changes in a single right ventricular dimension may not accurately reflect global right ventricular events. PMID- 2911186 TI - A new technique for use of an anomalous subclavian artery for a systemic pulmonary arterial shunt. AB - Anomalous subclavian arteries were used as interposition grafts for systemic pulmonary arterial shunts in three infants and children with good early and long term results. This is the first report of the use of an anomalous subclavian artery as an interposition graft for a systemic-pulmonary arterial shunt. The advantages and effectiveness of the technique are discussed. PMID- 2911187 TI - Gangrene of the lung. AB - Case histories of four patients with gangrene of the lung are presented. All of these patients had characteristic radiographic features of the disease. Two patients had resection and survived. One patient who spontaneously coughed up necrotic tissue via the bronchus survived. One patient who died of an acute myocardial infarction was found at autopsy to have the characteristic pathologic findings of gangrene of the lung. PMID- 2911189 TI - Acquired immunodeficiency syndrome, a complication of cardiothoracic surgery. AB - We identified 13 patients who contracted acquired immunodeficiency syndrome or human immunodeficiency virus-related disease after a cardiothoracic operation. The operations were performed between January 1981 and November 1984, and the diagnosis of human immunodeficiency virus-related disease was established from 26 to 54 months after operation. The survival time from diagnosis ranged from 8 days to 14 months in the 10 patients who have died. A clinical illness developed in three of the patients immediately postoperatively that was consistent with primary human immunodeficiency virus mononucleosis. The clinical features included a wide variety of opportunistic infections, but an abnormally high percentage of the patients first showed symptoms of dementia or neoplastic disease. In many patients, the diagnosis was not suspected for a prolonged period of time. On the basis of the prolonged incubation period, the incidence of this disease is likely to increase for several more years. PMID- 2911188 TI - Unusually low mortality of penetrating wounds of the chest. Twelve years' experience. AB - Within a 12-year period ending in March 1984, 1109 patients with penetrating thoracic injuries were treated at King-Drew Medical Center located in south central Los Angeles. The average age of the patients was 28.1 years. There were 607 stab wounds and 502 gunshot wounds. Antibiotic prophylaxis was prescribed only for the 428 patients who had laparotomy, thoracotomy, and pulmonary contusion with hemoptysis. Of the 1109 patients, 105 had cardiac injuries. All patients with cardiac trauma underwent thoracotomy, and the mortality rate was 18.1%. Specifically, the mortality rate of gunshot wound of the heart 24.5% and that of stab wound of the heart, 11.5%. In contrast, of the 1004 patients without cardiac injuries, only 115 required thoracotomy and the mortality rate in this group was 0.8% (8/1004). The mortality rate was 69.6% in patients who had a thoracotomy in the emergency room but only 2.8% in patients who had a thoracotomy in the operating room within the first 24 hours after admission. In the 242 patients who had associated abdominal injuries, the mortality rate was 2.1% (5/242), as compared with 2.5% (22/867) for those who had isolated chest injuries. In the entire group, the incidence of complications was 5.1%, of which 1.8% were infectious complications. The presence of associated abdominal injuries did not influence the outcome. The mortality rate in noncardiac thoracic injuries is very low compared with that of cardiac injury. Because of the complexity of the injury, gunshot wound of the heart has the highest mortality rate. PMID- 2911190 TI - Development of a new experimental model for total exclusion of the right heart without the aid of cardiopulmonary bypass. AB - A new experimental model for the total exclusion of the right heart was successfully developed in mongrel dogs without the use of cardiopulmonary bypass. A Y-shaped conduit was constructed with tube grafts spirally stented on the exterior (10 mm in diameter), and each upper limb of the conduit was provided with a 30F cannula. The foot of the conduit was anastomosed with the main pulmonary artery in an end-to-side way with a side clamp. After a closed atrioseptostomy was performed with a special knife of our design, the upper limbs of the graft were connected to the superior and inferior venae cavae by a cannulation method. The operative procedure was completed by tightening the occluding snares around the venae cavae and ligating the root of the pulmonary artery and azygos vein. Thus, without any use of the right atrium, venous blood from the venae cavae was totally diverted to the pulmonary circulation via the conduit, and only the coronary venous return was shunted to the left atrium. Five consecutive dogs tolerated the operative procedure. No pressure gradients were observed between the pulmonary arteries and venae cavae. The circulation with this model was able to be sufficiently sustained with mean pulmonary arterial pressures of about 25 mm Hg, and no significant changes were shown in the left ventricular pump function from the preoperative state. However, the decrease in the mean pulmonary artery pressure to 20 mm Hg resulted in severe circulatory failure, and two of the five dogs succumbed to this condition. Our new model will be useful for studying the hemodynamic characteristics of the circulation after operations that result in total exclusion of the right heart. PMID- 2911191 TI - Balloon electric shock ablation. Effects on ventricular structure, function, and electrophysiology. AB - We have recently developed a transatrial balloon approach for intraoperative endocardial mapping of ventricular tachycardia, which can be performed in the intact ventricle. In selected patients, we have eliminated the arrhythmia by passing a series of electric currents through specific beads on the balloon array. The goal of this new technique, balloon electric shock ablation, is to create a homogenous scar in the subendocardial target area identified by mapping. Experimental data exist on the effects of catheter delivery of electric discharges to the myocardium, but no data are available on the effects of balloon electric shock ablation. We have performed balloon electric shock ablation in animals (nine cathodal shocks of 100 J given through a 4 cm2 electrode grid). Ventricular function was assessed at 6 weeks and compared with function after a simple ventriculotomy and with function in control animals having no operation. Gated nuclear ventriculograms were obtained during volume loading. Myocardial performance and diastolic pressure volume relationships were determined for the three groups. After balloon electric shock ablation or ventriculotomy, left atrial pressures were increased at similar end-diastolic volumes, which indicated decreased ventricular compliance. The trend reached statistical significance (compared with data from control animals) only in the group undergoing balloon electric shock ablation. Myocardial performance (stroke work index/end-diastolic volume relationship) was unchanged in the three groups. In the long-term balloon electric shock ablation preparation, an electrophysiologic study (including burst pacing) failed to induce ventricular arrhythmias. At 6 weeks, the lesion created by balloon electric shock ablation was a layer of homogenous mature scar with sharply defined borders. There was no evidence of additional injury to the surrounding myocardium or to the mitral valve apparatus. These studies show that delivery of a series of electric shocks through a 1 cm balloon grid of electrodes can create an area of homogeneous, electrically inert scar and that this procedure when performed in healthy dog hearts has no significant effect on the structure and function of the rest of the left ventricle. PMID- 2911192 TI - Local excision of pulmonary nodular (coin) lesion with noncontact yttrium aluminum-garnet laser. AB - Local excision of pulmonary nodular lesions with the noncontact mode of the neodymium: yttrium-aluminum-garnet laser was done in 14 patients. This was achieved through a conventional limited thoracotomy and then by evaporation/fulguration of 0.5 to 1 cm of the healthy parenchyma surrounding the lesion, which produced a bloodless incision. In 10 patients the lesion was a primary (N = 7) or secondary (N = 3) malignant tumor. The remaining four had a benign nodule. Preoperative radiology has demonstrated a solitary nodule in all 14 patients, but at operation in four patients (three with benign and one with malignant disease) there were two nodules. In each of these four patients the smaller nodule was evaporated entirely, without excision of normal pulmonary tissue. There were no hospital deaths or postoperative complications. One patient died 8 months postoperatively (carcinomatosis); the other 13 remain alive and well between 2 and 25 months after treatment. We believe that local excision of nodular pulmonary lesions with the laser should be considered whenever possible, particularly in high-risk patients, those with limited respiratory function, and in the elderly. PMID- 2911193 TI - Intraoperative evaluation of ventricular tachycardia. PMID- 2911194 TI - Aortic arch thrombosis in the neonate. PMID- 2911195 TI - Surgical resection of high cervical esophageal carcinoma with malignant tracheoesophageal fistula: a case report. PMID- 2911196 TI - Elective deep hypothermia with total circulatory arrest: changes in plasma creatine kinase BB, blood glucose, and clinical variables. AB - Serial measurements of a marker of brain ischemia, creatine kinase isoenzyme BB, were performed in arterial and internal jugular venous blood from 20 infants younger than 1 year of age before and during the first 20 hours after deep hypothermic total circulatory arrest procedures. A two-site monoclonal method was used, and the results were analyzed in relation to age, size, type of cardiac lesion, hemoglobin level, blood glucose level, pH, and duration of the total circulatory arrest. The creatine kinase BB concentrations increased after the arrest, more so in venous than in arterial blood, from 3.2 +/- 0.5 ng/ml to 17.5 +/- 4.5 in arterial blood and from 3.5 +/- 0.5 ng/ml to 18.1 +/- 5.8 in venous blood. Arterial-venous concentration differences correlated with venous concentrations (r = 0.92, p less than 0.01). The duration of the arrest correlated with creatine kinase BB concentrations during reperfusion with correlation coefficients between 0.50 to 0.90 depending of what sequence of the 20-hour sampling period was analyzed. The best correlation was obtained during the first 4 hours of reperfusion. Age, size of the child, and preoperative cyanosis correlated with postoperative creatine kinase BB but were less important than the arrest time, blood glucose level (r = 0.62, p less than 0.01), pH (r = 0.78, p less than 0.01), and hemoglobin level (r = 0.76, p less than 0.01) during reperfusion. It is suggested that a different control of blood glucose level and pH during reperfusion may be of importance to reduce biochemical signs of cerebral dysfunction after deep hypothermic total circulatory arrest procedures. PMID- 2911197 TI - Functional and metabolic protection of the neonatal myocardium from ischemia. Insufficient protection by cardioplegia. AB - The effects of ischemia and cardiac arrest by cardioplegia on the mechanical function and energy metabolism of the ventricular myocardium of the neonatal guinea pig were investigated in the isolated perfused heart preparation and compared with these effects in the adult guinea pig. Whereas reperfusion after ischemia resulted in better recovery of mechanical function and a higher adenosine triphosphase content in the neonatal myocardium than in the adult, recovery from cardiac arrest induced by St. Thomas' Hospital cardioplegic solution was not as good in the neonatal myocardium as in the adult. Contracture developed in the neonatal myocardium on administration of the cardioplegic solution, but did not in the adult. This was considered to be the reason that the protective effect of the cardioplegic solution was inferior in the neonatal myocardium to that in the adult. PMID- 2911199 TI - Postinfarction ventricular septal defect. An efficacious technique for early surgical repair. AB - Between December 1982 and June 1987, seven consecutive patients (52 to 77 years old) underwent early surgical repair of postinfarction ventricular septal defect. The defect was diagnosed 3 to 10 days after the myocardial infarction. A new repair technique was used which stresses that no part of the infarcted septum be resected. This technique consists of a transinfarction incision in the left ventricle, placement of a fine Dacron fabric patch that covers all the infarcted septum and closes the ventricular septal defect, and placement of a second Dacron fabric patch that reinforces the infarcted anterior wall of the heart and supports the buttressed double suture closure of the left ventriculotomy. One very ill patient of this series died during the operation (mortality rate 14.3%). Three patients required the help of intraaortic balloon counterpulsation postoperatively, and five needed inotropic drug support. None of the patients had excessive bleeding. Two initial patients had a small left-to-right interventricular shunt. Postoperative angiographic studies and Doppler echocardiography confirmed the existence of a nonsignificant residual ventricular septal defect in these two patients and showed good geometry of the left ventricle with no aneurysm formation in all six survivors. This technique seems to be efficacious. It can be expeditiously performed, and the risks of postoperative complications related to the technique appear to be minimal. PMID- 2911198 TI - Difference in the mechanical response to a cardioplegic solution observed between the neonatal and the adult guinea pig myocardium. AB - We attempted in two types of preparations to delinate the difference in responses to St. Thomas' Hospital cardioplegic solution between the neonatal and the adult guinea pig myocardium. Isolated guinea pig hearts were perfused with Langendorff's method and the tension of the papillary muscle of the right ventricle was recorded. Continuous infusion of St. Thomas' Hospital cardioplegic solution (37 degrees C) for 30 minutes resulted in a significantly higher elevation of the resting tension (development of contracture) in the neonatal myocardium than in the adult. The recovery of normal contractile tension after the resumption of perfusion with normal Krebs-Ringer bicarbonate solution was smaller in the neonate with increases in the myocardial water and calcium contents. The membrane potential of the papillary muscle preparation was recorded by means of conventional glass microelectrodes. There was no significant difference in the control values of the resting membrane potential and in the degree of depolarization during exposure to St. Thomas' Hospital cardioplegic solution between the neonate and the adult. Thus the greater elevation of the resting tension produced in the neonatal myocardium by St. Thomas' Hospital cardioplegic solution was not due to a greater depolarization of the surface membrane. PMID- 2911200 TI - Leaflet fracture in Edwards-Duromedics bileaflet valves. AB - Two cases of leaflet fracture in the Edwards-Duromedics valve at 36 and 38 months after implantation are reported. Both patients were immediately reoperated on and recovered well. In one valve an older housing fracture with partial tissue ingrowth was noted beside a recent transverse leaflet fracture. In the other valve the leaflet was fractured near the pivot mechanism. All larger embolized parts were detected in the iliac artery region by computed tomographic scan and were subsequently removed. Problems in diagnosis and the importance of immediate reoperation, even without exact diagnosis, are discussed. Technical evaluation of the valve revealed crack growth and arrest, giving evidence of fatigue fracture. Scanning electron microscopic examination revealed several areas of pitting and erosion. Although the exact cause of mechanical disruption remains speculative, pyrolytic carbon seems to have the characteristic of fatigue fracture as well as erosion damage. A connection between the two might exist. PMID- 2911201 TI - Mechanical failure of the Bjork-Shiley valve. Updated follow-up and considerations on prophylactic rereplacement. AB - The early production series of the 29 to 31 mm 70-degree convexo-concave (CC70) Bjork-Shiley heart valves constitutes a subgroup of CC70 values with an extra high risk of outlet strut fracture. The hazard function for mechanical failure among these valves has remained almost constant over a 7-year follow-up period, and the 7-year actuarial incidence of mechanical failure among these valves is 12.5%. Selected patients with these valves will be considered for prophylactic rereplacement. PMID- 2911202 TI - Effects of desferrioxamine on normal and leukemic human hematopoietic cell growth: in vitro and in vivo studies. AB - The iron chelator desferrioxamine (DFO) has been previously shown to be an S phase inhibitor of cell proliferation. To investigate its potential as an antileukemic drug, we first studied the effects of DFO on the in vitro growth of normal human hematopoietic progenitors (CFU-GM and BFU-E) and clonogenic cells from human leukemic cell lines. Then we evaluated the effects of DFO on progression of leukemia refractory to conventional therapy in two individuals. Micromolar concentrations of DFO determined a dose-dependent inhibition of normal progenitor growth, with inhibitory dose 50% (ID50) for CFU-GM and BFU-E being 6.7 and 5.5 microM/liter, respectively. Marked inhibitory effects were observed on clonogenic cells from HL-60 (ID50 = 1.4 microM/liter) and U-937 (ID50 = 3.6 microM/liter) human leukemic cell lines grown in semisolid medium. When DFO was given intravenously to a patient with lymphoid blast crisis of chronic myelogenous leukemia, a marked reduction in circulating blast count was observed. On the contrary, no in vivo effect was observed in a patient with acute nonlymphocytic leukemia having transfusional iron overload. We conclude that: (a) DFO is an inhibitor of both normal and leukemic myeloid cell proliferation in vitro; (b) our limited in vivo observations and a previous case study suggest that intravenous administration of DFO to patients with normal to low plasma iron may result in leukemic cytoreduction in vivo. PMID- 2911203 TI - Prognostic value of immunological markers in acute myeloblastic leukemia. AB - In order to investigate the prognostic value of immunologic markers together with the most relevant clinical and hematological disease characteristics in acute myeloblastic leukemia (AML), the reactivity of blast cells from 102 patients with AML was analyzed with a panel of twenty monoclonal antibodies. The univariate analysis showed that five parameters had an adverse effect on both complete remission (CR) and survival: advanced age (greater than 60 years), anemia (hemoglobin concentration (Hb) less than 10g/dl), the expression of the antigens detected by the anti-megakaryocytic antibodies (CDw41/CDw42), the monocytic antibodies (CD14), and the CD9 (FMC56, FMC8) antigen. In addition, the failure to obtain CR had a significant adverse effect on survival (p less than 0.0001). Multivariate analysis showed that only age and Hb had a significant influence on CR while for predicting survival the most important independent prognostic factors were: CR, age, number of platelets and reactivity with the CD9 antibody. These results show that immunological markers could represent a valuable tool in the assignment of risk categories in AML patients. PMID- 2911204 TI - Phase II trial of intermediate dose ARA-C (IDAC) with sequential mitoxantrone (MITOX) in acute myelogenous leukemia. AB - Forty-seven patients with primary refractory, relapsed, and previously untreated, poor risk AML were entered into a phase II study of intermediate dose ARA-C (IDAC) (1 g/m2 i.v. over 6 hr, daily for 6 days) with sequential mitoxantrone (MITOX) (6 mg/m2 i.v. bolus 3 hr after the end of each ARA-C infusion). Overall, complete remission was induced in 31 patients (66%), and 1 additional patient entered a partial remission. Seven patients (15%) died of infection during marrow hypoplasia. Response to IDAC + MITOX was influenced by sensitivity to previous therapy: patients with primary refractory and early relapse AML responded less well to the regimen (CR rate 28% and 33%, respectively), as compared to those with previously untreated (CR rate 64%) or late relapse disease (CR rate 85%). Sixteen patients continue in CR at 1-12+ months. Except for the expected severe myelosuppression, the regimen was well tolerated with minimal extramedullary toxicity. The data indicate that the sequential combination of IDAC and MITOX is an effective and tolerable regimen for AML. Consideration should be given to applying this program at earlier stages of AML therapy. PMID- 2911205 TI - Comparative trial of cytarabine and thioguanine in combination with amsacrine or daunorubicin in patients with untreated acute nonlymphocytic leukemia: results of the L-16M protocol. AB - Ninety-six patients with de novo acute nonlymphocytic leukemia (ANLL) were randomized to receive either daunorubicin (50 mg/m2, IV) on days 1-3; cytarabine (Ara-C) (25 mg/m2, IV) bolus, followed by 160 mg/m2 as a continuous IV infusion daily for 5 days and 6-thioguanine (6-TG) (100 mg/m2 po) every 12 hr daily for 5 days (DAT); or amsacrine (190 mg/m2, IV) on days 1-3 with Ara-C and 6-TG at the above doses (AAT). Patients achieving complete remission (CR) then received two courses of consolidation therapy with the same combination that had induced remission but at slightly reduced total doses. Patients less than or equal to age 40 with an HLA-identical sibling donor underwent allogeneic transplantation, usually after consolidation therapy. The remaining patients were then randomized to receive either maintenance therapy (alternating cycles of vincristine/methotrexate, cyclophosphamide/6-TG, daunorubicin/hydroxyurea and Ara C/6-TG) or no further treatment. Ninety-two patients were evaluable for response. Twenty-five of the 46 patients (54%) who received DAT and 32 of the 46 patients (70%) who received AAT achieved CR (p = 0.13). When patients were stratified by age, however, remission induction advantage with AAT became statistically significant (p = 0.03). Additionally, more patients achieved CR following one course of AAT than following one course of DAT (48% vs 28%, p = 0.03). Overall survival in the AAT group was improved as well (p = 0.01). Too few patients were randomized on the maintenance arm of the protocol to make interpretation meaningful. Non-hematologic toxicity was generally comparable in both arms. In conclusion, patients with de novo ANLL who received AAT had a higher remission incidence and slightly longer survival compared to patients who received DAT. Further investigation of this drug combination in untreated patients with ANLL is warranted. PMID- 2911206 TI - Clonal immunoglobulin gene rearrangements in primary mediastinal clear cell lymphomas. AB - Cells from two patients with primary mediastinal tumors of clear cell type were characterized by immunological and molecular biological techniques. In both cases a B cell immunophenotype was suggested by the positive staining for the B1 (CD20), B4 (CD19), Leu 14 (CD22), as well as staining with other B monoclonal antibodies by immunohistochemistry. However, no definitive evidence for the expression of Ig light or heavy chains at the protein level was found. Southern blot analysis of Ig heavy and light chain gene rearrangements revealed clonal B cell populations in both cases. There was no indication of a somatic joining of T cell receptor (TCR) genes using probes for TCR beta and or TCR gamma genes. Thus, our results suggest a clonal B cell origin of clear cell lymphomas in the mediastinum. PMID- 2911207 TI - Human long-term bone marrow cultures (HLTBMCs) in myelomatous disorders. AB - Human long-term bone marrow cultures (HLTBMCs) were established with bone marrow (BM) collected from five patients with myelomatous disorders (four with multiple myeloma, one with plasma cell leukemia). In all cases, up to at least 6 weeks of culture, there was a persistence of the monoclonal plasma cell population in the adherent layer of the culture. In some cultures proliferating plasma cells could be demonstrated by the Ki-67 monoclonal antibody. In all instances a paraprotein could be shown in the conditioned medium. This study demonstrates that malignant plasma cells, in analogy to their normal counterparts, have an affinity for the BM stroma and suggests that their long-term survival might be enhanced by their interaction with it. PMID- 2911208 TI - Comparison of human long-term bone marrow cultures (HLTBMCs) established from fresh and post-cryopreservation bone marrow samples from living and cadaver donors. AB - Human long-term bone marrow cultures (HLTBMCs) were established from thawed post cryopreservation, as well as from cadaver donor bone marrow (BM) samples. The longevity was similar in the different series of HLTBMCs examined. CFU-GM could be cultured out of cadaver donor BM. This indicates that previously healthy people, under the conditions generally accepted as suitable for organ donation, could become suitable donors for allogeneic BM transplantation. PMID- 2911209 TI - Contemporary adolescent norms for the Minnesota Multiphasic Personality Inventory -one perspective. PMID- 2911210 TI - Serodiagnosis of Wegener's granulomatosis: pathobiologic and clinical implications. PMID- 2911211 TI - Superficial granulomatous pyoderma. PMID- 2911212 TI - Pepto-bismol and salicylate levels. PMID- 2911213 TI - Quinacrine-associated mania. PMID- 2911214 TI - Superficial granulomatous pyoderma: clinicopathologic spectrum. AB - Superficial granulomatous pyoderma is a form of pyoderma gangrenosum characterized by superficial ulceration and a chronic course. Histopathologic examination shows a granulomatous response. We report two new cases of superficial granulomatous pyoderma in detail and briefly review the clinical data of five previous cases included in a recent series. These lesions typically begin as single furunculoid papules that most commonly occur on the trunk and that may arise at sites of surgical treatment or other pathergic stimuli. The lesions progress to superficial ulcers with a relatively clean base and vegetative borders. Tetracycline, minocycline, sulfapyridine, dapsone, and intralesionally administered corticosteroids have been effective anti-inflammatory agents, producing healing and allowing avoidance of the use of systemic corticosteroids in the management of most patients with superficial granulomatous pyoderma. PMID- 2911215 TI - Idiopathic granulomatosis manifesting as fever of unknown origin. AB - Twenty patients with fever of unknown origin were found to have idiopathic granulomatosis of the liver, lymph nodes, spleen, or bone marrow. At the time of initial examination, these patients had persistent or recurrent fever and pronounced constitutional symptoms but few physical findings. The most common laboratory abnormalities were increased erythrocyte sedimentation rate in 18, abnormal results of liver function tests in 12, anemia in 11, and hypergammaglobulinemia in 10. Of the 20 patients, 14 required corticosteroids at the beginning of the illness for control of symptoms, especially fever. After 5 to 10 years of follow-up, an alternative diagnosis had been established in 5 of the 20 patients. Of the remaining 15 patients with fever and idiopathic granulomatosis, 6 are still receiving corticosteroids. Corticosteroid treatment did not result in progression or dissemination of an unrecognized infection. No clinical or laboratory abnormality helped to predict the need for long-term corticosteroid treatment. PMID- 2911216 TI - Carbon monoxide diffusing capacity of the lungs determined by single-breath and steady-state exercise methods. AB - We measured carbon monoxide diffusing capacity of the lungs (DL,CO) by both the resting single-breath (SB) and steady-state (SS) exercise methods in 95 patients referred for pulmonary function testing. A 10-second breath-holding method was used for the SB test. DL,CO (SS) was measured during the last minute of a 3 minute exercise test on a 9-inch step. Results of the two methods showed good agreement, the SB-SS difference averaging -0.70 (SD, 3.39) ml/min per mm Hg. The difference between the two methods was not correlated with other measurements of pulmonary function except minute ventilation during the exercise performed in the DL,CO (SS) procedure. In a separate study of laboratory personnel, the day-to-day variabilities of the two tests were similar (SD, 1.4 ml/min per mm Hg). Alveolar volume obtained by helium dilution during the SB test was comparable to total lung capacity (TLC) estimated by multiple-breath nitrogen washout in patients without severe airway obstruction. In severe airway obstruction, the mean SB alveolar volume was 13.8% less than the TLC by nitrogen washout, a difference that may be useful as an indicator of inefficiency of gas mixing in the lungs. We conclude that the SB and SS exercise methods provide similar estimates of DL,CO in patients referred to a pulmonary function laboratory. PMID- 2911217 TI - Does having more time after retirement change the demand for physician services? AB - Various aspects of the demand for ambulatory services of physicians have been studied by researchers, but so far the effect of increased availability of nonwork time due to retirement on demand has not been examined. This study investigated whether discouraging early retirement (which was the intent of the 1983 Amendments to the Social Security Act) will reduce the use of medical services because persons who continue to work have less time than retirees for visits to doctors. This study found that, for men whose health does not interfere with work and who have had no in-hospital care in the study year, retirement does not increase the demand for ambulatory services when compared with being a part time or full-time employee. However, compared with full-time self-employment, retirement increases the probability of using any physician services in the year by 14% and the number of physician visits by two visits. Although the self employed have more control over their work time than employees, they may be more affected than employees by the loss of output and earnings associated with absence from the workplace. PMID- 2911218 TI - Practice changes in response to the malpractice litigation climate. Results of a Maryland physician survey. AB - Data from a 1987 survey of Maryland physicians in three specialties (internal medicine, family or general practice, and obstetrics-gynecology) were used to study the types of changes physicians have made in their practices during the last 2 years as a result of the current malpractice litigation climate. Overall, 51% reported making some type of practice change. The practice changes that physicians reported reflect both risk-reduction (e.g., increased use of tests) and risk-avoidance (e.g., cutting back high-risk patients) strategies, although risk-reduction actions were reported more frequently. Raising patient fees was also reported. Specialty predicts whether or not physicians make each type of change; in particular, obstetrician-gynecologists are more likely to report practice changes of all types. Prior litigation experience does not, in general, predict practice changes. The implications of the types of changes reported for access to care and costs of care were considered. PMID- 2911219 TI - Methods of analyzing physician practice patterns in hypertension. AB - A principal method of studying physician practice patterns has been to examine physicians' responses to brief written cases. We have compared this method with practice patterns of the same physicians derived from chart audit. Subjects were 98 family practice residents for whom data were available in actual patient encounters for the workup of asymptomatic hypertension. Short, carefully structured case reports using four cues were designed and a checklist similar to the one used for test ordering in practice was employed. Chart reviews and billing encounter forms were used for comparison. Results indicated residents ordered fewer tests in clinical practice, due, in part, to practice constraints not represented in the written cases. Physicians tend to make the diagnosis of hypertension incrementally in practice, with no one visit adequately representing the point of diagnosis. Studies based on data bases using a patient encounter as the unit of analysis in chronic disease such as hypertension may spuriously underestimate the actual number of tests ordered for the workup. Judgment cases may better reflect the patterns of use of information in a well-defined problem. Prediction of number of tests ordered in the clinical setting has not been established in this case. PMID- 2911220 TI - Psychiatric severity of illness. A case mix study. AB - This study was undertaken to determine if a measure of severity of illness for psychiatric patients, the Psychiatric Severity of Illness Index, could produce psychiatric case mix groups that are more homogeneous with respect to resource use than the diagnosis-related groups (DRGs). Psychiatric Severity of Illness data were collected on 1,672 cases in ten hospitals of various types. Of these cases, 1,418 had enough information in the medical record to be scored using the Psychiatric Severity Index, 1,173 of which were in MDC 19 (mental diseases and disorders). We found that four Psychiatric Severity of Illness groups explained between 34% and 50% of the variation in length of stay of the combined hospital data in MDC 19, whereas nine DRGs explained between 6% and 14%. DRGs subdivided by Psychiatric Severity of Illness groups explained between 40% and 54% of the variation in length of stay. The implications of these results for cross-hospital comparisons are discussed. PMID- 2911221 TI - Substitution between prescribed and over-the-counter medications. AB - Using data from the Health Insurance Experiment (HIE), this article examines use of over-the-counter drugs (OTC) in a general, nonelderly population. Families from six areas of the country were assigned to health insurance plans that varied in the amount of medical care cost sharing. Thus, the out-of-pocket prices of OTC relative to prescription drugs were experimentally varied. The sites were chosen to represent markets with differing access to physician services. Multivariate methods were used to relate OTC use (collected from bi-weekly health diaries) to cost sharing and demographic variables. The empirical results do not support the expectation that people assigned less generous insurance for prescription drugs substitute OTC for prescriptions. People with complete insurance coverage purchased more of both types of drugs, suggesting OTC are an adjunct to formal medical care, rather than a substitute for it. Better educated and more knowledgeable consumers used more OTC drugs and spent more of their drug budget on OTC products. That there was greater OTC drug use in HIE sites with poorer access to formal medical care suggests there was some substitution between formal care and self-care with OTC drugs. Overall, however, better financial access to formal care promotes rather than substitutes for OTC use. PMID- 2911222 TI - Diagnosis and prevalence of obesity. AB - Obesity is a condition of increased adipose tissue mass. Many techniques are available for measurement of body fat, but none is available widely for clinical purposes. The new technique of bioelectrical impedance may change this in the future. For now, relative weight and BMI are used as indices of obesity, which may be defined as a BMI greater than 30 kg per m2. This corresponds to a relative weight approximately 120 per cent above desirable. According to this definition, obesity exists in 10 to 12 per cent of adult men and women in the United States and Canada. PMID- 2911223 TI - Physiological regulation of body weight and the issue of obesity. AB - The relationship described here between resting energy expenditure and the body weight set-point provides a framework for assessing an animal's regulatory status. Procedures based on this relationship have been used to evaluate the status of rats whose obesity was either of dietary or hypothalamic origin. In dietary obese rats, the body weight set-point appears to have elevated. Their normal rate of energy expenditure at an elevated weight, as well as their active adjustments of expenditure in defense of their obesity, supports this conclusion. Hypothalamic obese rats, in contrast, neither expend energy at a rate normal for their body mass nor display the adjustments in expenditure appropriate to defending their obesity. From these observations, a distinction is drawn between regulated and unregulated forms of obesity. It is suggested that weight disorders in humans, particularly obesity, may be amenable to similar sorts of analysis and categorization, eventually leading to the development of therapies appropriate to the specific type or form indicated. PMID- 2911224 TI - [Progress of alcohol consumption and alcohol-related damages in Sweden]. PMID- 2911225 TI - [A cultural shock upon returning to Sweden with its drinking habits after a year in Arabic countries]. PMID- 2911226 TI - [Improve the rights and care of abused children]. PMID- 2911227 TI - [Future drug committees--institutions for cooperation and information]. PMID- 2911228 TI - [Screening of cancer in ulcerative colitis]. PMID- 2911229 TI - [It is not proved that the HIV/AIDS risk influences the sex behavior of the population]. PMID- 2911230 TI - [Increased knowledge after every survey]. PMID- 2911231 TI - [Amalgam poisoning--a medical reality]. PMID- 2911232 TI - [Is it possible to teach high school pupils resuscitation?]. PMID- 2911233 TI - [Acute aortic occlusion--management and prognosis]. PMID- 2911235 TI - [Functional respiratory disorders as significant differential diagnosis in asthma]. PMID- 2911234 TI - [Acute and chronic renal artery occlusion--etiology and therapeutic possibilities]. PMID- 2911236 TI - [Have buying restrictions any place in Swedish alcohol policy?]. PMID- 2911237 TI - [Support integrity of nurses]. PMID- 2911238 TI - [Height and weight--a question of interpretation?]. PMID- 2911239 TI - [Laparotomy is a better method in the treatment of intra-abdominal infections]. PMID- 2911240 TI - [The unsolved case of ulcerations in the small intestine--what happened later on?]. PMID- 2911241 TI - [Good results after non-pharmacologic treatment of hypertension provided by health centers]. PMID- 2911242 TI - [Non-pharmacologic treatment is an effective method in hypertension]. PMID- 2911243 TI - [How long is the necessary duration of antibiotic treatment?]. PMID- 2911244 TI - [Medical ethics. Ethical problems of psychiatric surgery from the philosophical point of view]. PMID- 2911245 TI - [Favourable surgery of cervical neck instability in rheumatism]. AB - A team project commenced 20 years ago can now present results of 150 surgical stabilising procedures for cervical neck instability in rheumatoid arthritis. The favourable results indicate widened indications. MR examination demonstrated regression of soft tissue swelling ("pannus") after surgery, which possibly contributed to the good results. PMID- 2911247 TI - [The fight against doping intensifies. Only the careless get caught today]. PMID- 2911246 TI - [Fertility surgery. A method for estimating pregnancy outcome]. PMID- 2911248 TI - Comments on a commentary. PMID- 2911249 TI - On the clinical significance of hindsight bias. PMID- 2911250 TI - Dexamethasone for bacterial meningitis in children. PMID- 2911252 TI - The Viralizer for the common cold. PMID- 2911251 TI - Tiopronin for cystinuria. PMID- 2911253 TI - Ataxia-telangiectasia: a variant with altered in vitro phenotype of fibroblast cells. AB - The clinical and cellular phenotype of ataxia telangiectasia (AT) has been extensively documented in numerous patients of different ethnic groups and is characterized by several specific laboratory hallmarks, such as chromosomal instability, profound radiosensitivity and radioresistant DNA synthesis. Several recent reports have, however, shown variations on this theme. This article describes 2 Turkish siblings with AT, who showed a typical but somewhat more prolonged clinical course of the disease and altered characteristics of fibroblast cells, compared to the 'classical' AT cellular phenotype. Fibroblast strains derived from these patients showed a normal cellular life span, moderate degrees of chromosomal instability and sensitivity to the lethal effects of X rays and neocarzinostatin, and lack of radioresistant DNA synthesis. A compilation of the literature on 'AT variants' and 'AT-like' syndromes shows that in addition to the internal variability of AT, this disease occupies a limited segment within a large spectrum of clinical and cellular features, which are common to a variety of syndromes. Each of these syndromes covers a different segment in this spectrum. The genetic basis of this family of disorders might be complex. PMID- 2911254 TI - Shuttle vector system for the analysis of mutational events in mammalian chromosomal DNA. AB - cDNA of the human hprt gene was introduced into the BamHI cloning site of the retroviral shuttle vector pZipNeoSV(X)1. The mouse cell line 2TGOR, a hypoxanthine phosphoribosyltransferase-deficient derivative of Balb/c 3T3, was transformed with the vector and some stably transformed HATrNEOr clones were established. One of the clones, VH-12, contained a single copy of the vector integrated stably into a chromosome in a proviral form. From this clone, we were able to recover efficiently the vector sequence preserving its intact structure by use of COS cell fusion. The relatively small size of the hprt cDNA (657 base pairs for the coding region) allowed quick determination of the entire DNA sequence. It was also notable that use of 6TG NEO double selection for mutant isolation could eliminate the 6TGr derivatives of VH-12 cells which arose from loss of the total vector sequence or from some epigenetic event, because such alterations would lead to inactivation of the neo gene as well as the hprt cDNA. The properties of our shuttle vector system were particularly useful for analysis of the molecular mechanisms of mutational events in chromosomal DNA of mammalian cells. PMID- 2911255 TI - The role of short-lived lesions in the induction of micronuclei in rat liver by ethylnitrosourea and methyl methanesulphonate: the importance of experimental design. AB - Rats received single injections of ethylnitrosourea (ENU) or methyl methanesulphonate (MMS) at the peak of DNA synthesis after partial hepatectomy. Hepatocytes were isolated 1-4 days later, and analysed for presence of micronuclei. With both chemicals, frequencies of micronucleated hepatocytes were increased in a dose-dependent manner, but ENU proved to be both more effective (6 times; based on molar dose) and more efficient (18 times; based on total DNA alkylation) than MMS. In general, the micronucleus frequency was relatively low at 1 day after injection, then increased to reach a maximum at days 2 or 3 (depending on the dose), after which it decreased strongly in case of MMS or remained stable in the case of ENU. The result with ENU is interpreted as a balance between loss and/or dilution of micronucleated hepatocytes and simultaneous formation of new ones. The present observations are in line with our earlier conclusion that ENU, in contrast with MMS, is able to induce persistent preclastogenic lesions in rat hepatocytes. ENU also proved to be more effective and efficient than MMS with respect to the formation of micronuclei in bone marrow cells. Our results with ENU and MMS indicate that administration of the genotoxin at the peak of DNA synthesis after partial hepatectomy, instead of before hepatectomy, increases the sensitivity of the liver micronucleus assay at least in the case of directly acting chemicals. PMID- 2911256 TI - Gene deletion, a mechanism of induced mutation by arabinosyl nucleosides. AB - 9-beta-D-Arabinofuranosyl-2-fluoroadenine (F-ara-A) and 9-beta-D arabinofuranosyladenine (ara-A) are purine nucleoside analogues which are incorporated into nucleic acids. This study demonstrates the mutagenic properties of F-ara-A and ara-A and provides evidence for mechanisms by which the arabinosyl nucleosides induce mutation. At the drug dosages that evoked exponential cell killing, F-ara-A and ara-A caused a significant increase in the number of 6 thioguanine-resistant mutants in Chinese hamster ovary cells. Southern analyses showed that 15 of 16 drug-induced mutants had lost all or part of the HPRT gene, whereas no loss of the gene was found in 4 spontaneous mutants. We conclude that both F-ara-A and ara-A induced mutation predominantly by causing deletion of genetic material. The remarkable frequency of gene deletion among these drug induced mutations is discussed with respect to possible mechanisms of action of arabinosyl nucleosides in mutational studies. PMID- 2911257 TI - Chromosome malsegregation and embryonic lethality induced by treatment of normally ovulated mouse oocytes with nocodazole. AB - The mouse egg is ovulated with its nucleus arrested at the metaphase-II stage of meiosis. Sperm entry triggers the completion of the second meiotic division. It has been speculated that damage to the meiotic spindle of normally ovulated eggs at around the time of sperm entry could result in chromosome malsegregation and the death of conceptuses with numerical chromosome anomalies. This hypothesis was tested using nocodazole, a microtubule inhibitor. Nocodazole was administered either to maturing preovulatory oocytes or to normally ovulated eggs at one of the following stages: (1) the time of sperm entry, (2) early pronuclear stage, (3) pronuclear DNA synthesis, (4) prior to first cleavage division, (5) early 2 cell stage, or (6) prior to the second cleavage division. Little or no effect was observed for treatment times other than the time of sperm entry, when the egg is being activated to complete the second meiotic division. Remarkably high frequencies of embryonic lethality, expressed at around the time of implantation, were induced at this stage. Cytogenetic analysis of first cleavage metaphases of zygotes treated at the time of sperm entry revealed a high incidence of varied numerical chromosome anomalies, with changes in ploidy being predominant. PMID- 2911258 TI - Lack of effect of maternal age on UV-induced DNA repair in mouse oocytes. AB - Oocytes at the dictyate stage from young (8-14 weeks) and old (12-15 months) BALB/c mice were manually isolated and UV-irradiated. They were cultured for 1 h in medium containing tritiated thymidine and chased for a further hour in cold thymidine medium before being incubated for 18-20 h in medium with no added thymidine. Oocytes which had developed to metaphase II were analysed following autoradiography. Pooled results from 14 replicate experiments revealed no significant age-related difference between the mean corrected grain count per cell [159.2 +/- 8.5 (86 cells) for young mice and 164.6 +/- 9.8 (70 cells) for the old animals]. Thus in the female mouse the oocyte's capacity to repair UV induced damage is apparently maintained at a high level throughout reproductive life. PMID- 2911259 TI - Effects of 50-hertz electromagnetic fields on proliferation and on chromosomal alterations in human peripheral lymphocytes untreated or pretreated with chemical mutagens. AB - Cultivation of human peripheral lymphocytes (HPL) in the presence of 50-Hz electromagnetic fields (EMFs) does not alter the spontaneous frequencies of sister-chromatid exchanges (SCE) and of chromosomal aberrations (CA), but leads to an enhancement of the cell cycle progression of HPLs in vitro. Pretreatment of HPLs with trenimon (TRN), diepoxybutane (DEB), or methylnitrosourea (MNU) in the G0 phase of the cell cycle results in dose-dependent elevations of the SCE frequencies. In some cases culturing of HPLs pretreated with MNU or TRN in the presence of EMFs led to significantly higher frequencies of SCEs when compared to cells cultivated in the absence of EMFs. Since we did not use multiple fixation times these data may rather result from differential influences on HPL subsets than from EMF exposure. PMID- 2911260 TI - Fetal anomalies produced subsequent to treatment of zygotes with ethylene oxide or ethyl methanesulfonate are not likely due to the usual genetic causes. AB - Earlier studies in this laboratory revealed that ethylene oxide (EtO) or ethyl methanesulfonate (EMS) induced high frequencies of midgestation and late fetal deaths, and of malformations among some of the surviving fetuses, when female mice were exposed at the time of fertilization of their eggs or during the early pronuclear stage of the zygote. Effects of the two mutagens are virtually identical. Thus, in investigating the mechanisms responsible for the dramatic effects in the early pronuclear zygotes, the two compounds were used interchangeably in the experiments. First, a reciprocal zygote-transfer study was conducted in order to determine whether the effect is directly on the zygotes or indirectly through maternal toxicity. And second, cytogenetic analyses of pronuclear metaphases, early cleavage embryos, and midgestation fetuses were carried out. The zygote transplantation experiment rules out maternal toxicity as a factor in the fetal maldevelopment. Together with the strict stage specificity observed in the earlier studies, this result points to a genetic cause for the abnormalities. However, the cytogenetic studies failed to show structural or numerical chromosome aberrations. Since intragenic base changes and deletions may also be ruled out, it appears that the lesions in question induced in zygotes by the two mutagens are different from conventional ones and, therefore, could be a novel one in experimental mammalian mutagenesis. Alternatively, the mechanism could involve a non-mutational 'imprinting' process that caused changes in gene expression. PMID- 2911261 TI - Detection of 6-thioguanine resistance in human peripheral blood lymphocytes (PBL) of industrial workers and lung cancer patients. AB - Human peripheral blood lymphocytes (PBL) were selected for 6-thioguanine (6-TG) resistance in short-term (42-h) cultures in 110 high-cancer-risk industrial workers, 131 primary lung cancer patients and 96 low-risk controls. The lymphocytes were cultured and stimulated by phytohemagglutinin (PHA). A labeling index (LI) was scored using light microscope autoradiography, based on the lymphocyte's ability to incorporate tritiated thymidine with or without selective agent 6-TG. The number of 6-TG-resistant cells increased in the high-occupational cancer-risk group of vinyl chloride- and mixed organic industrial dust (MOID) exposed workers as well as in the primary lung cancer patients. The results were compared with the low-occupational-cancer-risk groups and with samples taken from the 70 healthy individuals and 26 hospitalized, non-cancerous controls. In both risk-exposed groups the frequency of 6-TG-resistant lymphocytes was significantly higher (p less than 0.01) than in the controls. These results suggest that the original Strauss and Albertini (1977, 1979) method can be used to study qualitative risk assessment in carcinogen- or mutagen-exposed occupational groups. PMID- 2911262 TI - Radiosensitivity of lymphocytes from patients with Alzheimer's disease. AB - The response after gamma-irradiation of lymphocytes from 8 patients with Alzheimer's disease (AD), 3 patients with Huntington's disease and 13 normal subjects to stimulation by phytohaemagglutinin (PHA) was assayed by incorporation of [3H]thymidine. The response of non-irradiated cells was found to be significantly lower in AD cells than in age-matched normals but not significantly lower in old normals than in young normals. However, the response of irradiated cells to PHA, expressed as a percentage of that in non-irradiated cells, was found to be similar in AD patients, young and old normals and in HD patients. PMID- 2911263 TI - Photoreactivation rescue and dark repair demonstrated in UV-irradiated embryos of the self-fertilizing fish Rivulus ocellatus marmoratus (Teleostei; Aplocheilidae). AB - The effects of photoreactivation (PR) rescue and dark repair on the survival of UV-irradiated embryos of the hermaphroditic fish (Rivulus ocellatus marmoratus) are reported. When UV-irradiated embryos were illuminated by photoreactivating light (PRL) from fluorescent lamps, survival at the hatching stage was markedly increased. The maximum recovery to UV damage was shown by embryos that were exposed to PRL for at least 6 h after UV irradiation. The effect of PRL decreased 30 min after UV irradiation and no PR rescue was detected beyond 96 h. Treatment with 2 mM caffeine for 48 h after UV irradiation increased the sensitivity of the embryos in the dark. The above results demonstrate that Rivulus embryos have an efficient PR system and a caffeine-sensitive dark repair capacity. PMID- 2911264 TI - Nuclear DNA synthesis is blocked by UV irradiation in Dictyostelium discoideum. AB - We have used a thymidine auxotroph of the simple eukaryote, Dictyostelium discoideum and alkaline sucrose gradients of isolated nuclei to study alterations in DNA synthesis following irradiation of replicating haploid cells with 254 nm UV light. Three responses were characterized using pulse-chase protocols: (1) Lags in DNA synthesis as measured by the amount of label incorporated were 4, 9, and 20 h after 10, 50, and 200 J/m2. (2) The DNA synthesized during a 15-min pulse immediately after irradiation was of lower single strand molecular weight: 7, 3.5, and 3 x 10(6) dalton after 0, 50, and 200 J/m2. (3) The time required for maturation of the nascent DNA to full-sized single strands of about 2 x 10(8) dalton was 45-50 min for unirradiated cells, 3 h after 10 J/m2, and 20 h after 200 J/m2. The DNA of the irradiated cells did not mature uniformly during these delays; instead, a period of no increase in size was followed by a rapid, nearly control rate of maturation. We conclude: (a) at least some UV lesions block elongation of replicons; (b) the elongation of the replicons and their subsequent joining to yield mature high molecular weight DNA occurs after most of the lesions are repaired; (c) the timing of the different aspects of recovery suggest that initiation of replication is also inhibited. PMID- 2911265 TI - Existence and expression of photoreactivation repair genes in various yeast species. AB - Photoreactivation repair (Phr) activities in cell extracts of 13 different yeast species were measured by the Haemophilus influenzae transformation assay. Five species including Schizosaccharomyces pombe showed no or low enzymatic activity. In contrast to the other species, chromosomal DNAs of these 5 species did not show detectable hybridization using a DNA fragment of the photolyase PHR1 gene of Saccharomyces cervisiae as a probe even at a low stringency condition. When the PHR1 gene was attached to the 5'-flanking sequence of the iso-1-cytochrome c (CYC 1) gene of S. cerevisiae and introduced into S. pombe cells, the transformants acquired a high Phr activity, indicating that the PHR1 gene alone can provide a Phr-negative species with this repair activity and the light-absorbing cofactor(s) must be present in S. pombe. Our results also demonstrated that the 5'-flanking sequence of the S. cerevisiae CYC-1 gene works in S. pombe as a regulatory element. PMID- 2911266 TI - Protective role of potentially lethal damage repair in the neoplastic transformation of Balb/c 3T3 cells treated with N-methyl-N'-nitro-N nitrosoguanidine. AB - To determine the role of repair of potentially lethal damage (PLD) in the initiation process of neoplastic transformation, Balb/c 3T3 cells treated with N methyl-N'-nitro-N-nitrosoguanidine (MNNG) were temporarily exposed to conditioned medium obtained from density-inhibited Chinese hamster cell cultures, as a post treatment for the induction of PLD repair. With or without this exposure, cell survival and transformation frequencies were simultaneously determined by colony formation and focus-formation assays, respectively. Temporary exposure to conditioned medium resulted in a 20-30% increase in cell survival compared with no exposure. Post-treatment with conditioned medium resulted in a 60-65% reduction in transformation frequencies. At the molecular level, the repair of MNNG-induced single-strand breaks of DNA occurred much more rapidly in conditioned medium. These data suggest that PLD repair reduces the in vitro neoplastic transformation through excision repair operative during the cessation of DNA replication. Thus, PLD repair appears to be preventive against neoplastic fixation in initiation of neoplastic development. PMID- 2911267 TI - Enhancement of UV-induced mutagenesis and sister-chromatid exchanges by nickel ions in V79 cells: evidence for inhibition of DNA repair. AB - With regard to contradictory results concerning the mutagenicity of nickel compounds in short-term assays, especially in bacterial test systems, Chinese hamster V79 cells were used to measure mutagenicity, comutagenicity and the induction of sister-chromatid exchanges (SCEs) by NiCl2. We confirmed the induction of mutations at the HGPRT locus as well as SCEs. In addition, NiCl2 shows a pronounced comutagenic effect towards UV. When using confluent cultures or resting cells due to serum deprivation, where more time is given for repair processes, the comutagenic effect is higher compared to logarithmically growing cells (10 and 4 times, respectively, compared to twice). Hence, we attribute this enhancement in mutagenicity to inhibition of DNA repair. Also the increase in induced SCEs after combined treatment with UV and NiCl2 supports this thesis. Furthermore, NiCl2 enhances the cyto-toxicity of cis-DDP about 12-fold. Since no comutagenic effect is observed in combination with MMS, we suggest that the inhibition of DNA repair by Ni(II) applies to all DNA changes that are repaired by the 'long-patch' excision repair system. This inhibition may occur via replacement of other divalent metal ions essential in repair and regulation processes. PMID- 2911268 TI - Chromosomal instability in an oxygen-tolerant variant of Chinese hamster ovary cells. AB - Background levels of chromosomal aberrations and sister-chromatid exchanges (SCEs) were determined in CHO-99 cells, an oxygen-tolerant variant substrain of Chinese hamster ovary (CHO-20) cells capable of stable proliferation under an atmosphere of 99% O2/1% CO2, a level of hyperoxia at which cultured mammalian cells normally cannot survive. The mean chromosomal aberration frequency in CHO 99 cells was as high as 1 aberration per cell (mainly chromatid and chromosome gaps and breaks) versus 0.05 aberration/cell in CHO-20 cells, while the SCE frequency was 1.7- to 2.1-fold increased. While most aberrations were apparently distributed at random over the chromosomes, up to 31% of the aberrations appeared to be involved in site-specific fragility at a homologous site in chromosomes Z3 and Z4. Immediately upon shifting CHO-99 cells to air-equilibrated conditions their SCE frequency decreased to the control level, whereas the aberration rate persisted at a still elevated level of 0.16-0.31 aberration per cell, even after a culture period of 14 weeks under normoxia. This indicates that at least part of the chromosomal instability is a constitutional property of the variant cells, i.e., not directly dependent upon hyperoxic stress. In CHO-99 X CHO-20 hybrids the occurrence of chromatid-type aberrations and fragile site but not that of chromosome-type aberrations was suppressed under normoxic conditions, suggesting that chromatid-type aberrations and fragile site expression on the one hand and chromosome-type aberrations on the other hand are mediated by different constitutional defects in CHO-99 cells. No gross alterations in (deoxy)ribonucleoside triphosphate pools were detected in CHO-99 cells that could be held responsible for their chromosomal instability. In addition, no increased level of DNA damage was detected by the technique of alkaline elution. The excessive chromosomal instability in CHO-99 cells, as observed under hyperoxic conditions, may originate from reactive intermediates giving rise to DNA double strand breaks and/or a type of DNA lesion that is resistant to the conditions of the alkaline elution technique. However, alternative mechanisms based upon reactive species interfering with DNA replication/repair processes cannot be excluded. PMID- 2911269 TI - Human lymphocytes aged in vivo have reduced levels of methylation in transcriptionally active and inactive DNA. AB - The amount of 5-methylated cytosine (5 mC) in the sequence CmCGG has been measured in DNA extracted from uncultured peripheral blood human lymphocytes obtained from 24 young (mean age 25) and 22 old (mean age 75) individuals. When compared with the young group the old group had significantly reduced levels of 5 mC in total genomic DNA, in transcriptionally active DNA, and in genomic DNA from which transcriptionally active sequences had been removed. In both the young and old groups transcriptionally active DNA contained 10% less 5 mC than the residual 'inactive' DNA. These results indicate that loss of genomic DNA methylation may be involved in aging in vivo and underscore the association of gene regulation with the distribution of methylation in DNA. PMID- 2911270 TI - Age-associated changes in DNA methylation and mRNA level of the c-myc gene in spleen and liver of mice. AB - Age-associated changes in DNA structure and mRNA level were studied for the c-myc gene in spleen and liver of mice at 2, 14 and 26 months of age. Neither amplification nor rearrangement of the gene was detected in either tissue at any age. However, a significant alteration was observed in the methylation profile. The profile of the gene and its vicinity was determined using various methylation sensitive restriction enzymes. In both tissues, the gene had an unmethylated domain ranging from -2 kb upstream of the 5' end of the first exon to the 3' end of the first intron. It was flanked by partially methylated regions, where age dependent changes as well as tissue specificity were observed. In the spleen, age related hypomethylation was observed at both the 3' and 5' sides of the domain. In contrast, hypermethylation was found in the liver only at the 3' side. The steady-state level of c-myc mRNA showed a drastic decrease in liver from youth to middle age, while splenic mRNA changed little. The correlation between the changes of mRNA and DNA methylation is discussed. PMID- 2911271 TI - Age and strain dependence of O6-methylguanine DNA methyltransferase activity in mice. AB - The activity of the DNA repair protein O6-methylguanine DNA methyltransferase (MT) was compared in liver extracts from female ICR and male C57BL/6 mice at various ages (3-130 weeks old). Similar patterns of overall enzyme activity were observed in both strains with O6-MT activity being relatively low in young mice (3 or 8 weeks old). However, the activity significantly increased after adolescence (middle age), thereafter decreasing with old age (over 100 weeks old) to a level equivalent to that found in young mice. In an additional strain difference study, O6-MT activities in liver extracts from 4 strains of mice were compared at 5 and 30 weeks of age. Although a similar age-associated increase of enzyme activity in adolescence was confirmed in all 4 strains investigated, the closed-colony ICR mice differed from the inbred strains in demonstrating significantly higher levels of O6-MT activity in females than in males. However, the same tendency was also observed in a comparison of the sexes in 30-week-old C3H/HeN, C57BL/6 and BALB/c mice. PMID- 2911272 TI - Chromatin and nucleolar changes in Xeroderma pigmentosum cells resemble aging related nuclear events. AB - Xeroderma pigmentosum (XP) is a hereditary disease characterized by a defect in the excision-repair mode of ultraviolet light damage and a high incidence of skin tumors. Cultured fibroblasts from normal and XP cells at low population doubling times were compared by induction of mild spreading of their nuclear constituents in a highly alkaline solution containing detergent and formaldehyde. In each XP culture a certain fraction (10-80%) of the nuclei were abnormal (50-80% in cell lines from children with XP-C disorders and 10-35% from embryonic and adult XP cells). Although their chromatin threads appeared normal in structure, they were separated by intervals up to 5 times the normal spacing. In all XP cells having this abnormal spacing in the chromatin, fibrils of nucleolar origin were approximately doubled in thickness, denser and less tufted, and nucleolar granules were few and dispersed. We suggest that this study reveals an abnormal weakness of the chromatin in some XP cells which results in the breakage of some DNA fibers in our preparative alkaline conditions. This weakness may be related to single-stranded breaks induced by metabolism of a high level of active oxygen species. These nuclear changes in XP cells are similar to those which have been associated with normal or pathologic senescence. PMID- 2911273 TI - Nicotinamide adenosine dinucleotide level in dimethylsulfate-treated or UV irradiated mouse epidermis. AB - The level of nicotinamide adenosine dinucleotide (NAD) has been determined in the epidermis of 30 mice. Its value is 0.63 +/- 0.15 microgram/mg protein. Upon treatment with dimethylsulfate (DMS), the level of NAD drops in a dose-dependent fashion. This diminution is reversible when low doses of DMS are used. Upon irradiation with ultraviolet light, the level of NAD drops in the irradiated epidermis, the threshold of saturation being below 1200 J/m2. There is also a drop in the level of NAD in the epidermis protected against irradiation with a black rubber sheet. PMID- 2911274 TI - Mitochondrial DNA rearrangements are correlated with a delayed amplification of the mobile intron (plDNA) in a long-lived mutant of Podospora anserina. AB - A new long-lived mutant of Podospora anserina has been isolated and characterized. Its longevity is maternally inherited as revealed by reciprocal crosses. A molecular analysis resulted in the identification of an amplified DNA species (designated pAL2-1) with homology to mitochondrial DNA (mtDNA). The presence of this DNA species is correlated with mtDNA rearrangements and a delayed amplification of the mobile intron (plDNA). PMID- 2911275 TI - Frequencies of chromosomal aberrations in smokers exposed to pesticides in cotton fields. AB - Blood samples were collected from 50 smokers who were exposed to the pesticides DDT, BHC, endosulfan, malathion, methyl parathion, monocrotophos, quinolphos, dimethoate, phosphomidon, cypermethrin and fenvelrate. Samples were also collected from 20 non-smokers (control I) and 27 smokers (control II) who were unexposed to pesticides. Control II showed a significant increase in chromosomal aberrations when compared to control I. There was a significant increase in total chromosomal aberrations in smokers exposed to pesticides when compared to unexposed populations. PMID- 2911276 TI - Fixed and temporary fluctuations in the cell cycle of monomorphic lines of Trypanosoma brucei gambiense. AB - The growth rate of a cloned, monomorphic strain of Trypanosoma brucei gambiense can be changed in both fixed and environmentally induced ways. The purpose of this study was to determine which phases of the cell cycle were affected by these changes in generation time. A slow-growing cloned line of T. b. gambiense and its fast growing, cloned derivative, were collected from immunosuppressed mice at low parasitemias. The percentages of cells in G1, S, and G2-M phases were determined by cytophotometric measurements of nuclear DNA. The percentages of cells in late G2-M and D phases were established by light microscopy. Over 70% of the fixed reduction of generation time in the cell cycle of the fast growing trypanosome occurred during G1, the remainder in G2. Apparently, the parasite had genetically altered a metabolic pathway necessary for both the initiation of DNA replication and karyokinesis. Both fast and slow growing trypanosomes significantly decrease their growth rates at high parasitemia levels in immunosuppressed rodents. To determine which phases of the cell cycle were affected, nuclear DNA of T. b. gambiense collected at low and high parasitemias were compared. Over 60% of the increase occurred during the S-phase, the remainder in G1. Apparently, DNA replication was affected by the parasite load. Finally, these monomorphic strains of T. b. gambiense, like tumors, apparently do not have a noncycling (G0) phase or a restriction point in G1 since slow growing trypanosomes in either optimal or suboptimal conditions did not accumulate in a diploid state or proceed through S to D phases in a constant length of time. PMID- 2911277 TI - Cysteine-rich variant surface proteins of Giardia lamblia. AB - Surface antigenic variation was previously demonstrated in vitro and in vivo using Giardia lamblia isolate WB. To determine whether other isolates undergo similar changes, isolates GS and N were cloned and exposed to cytotoxic anti isolate sera or monoclonal antibodies (MAbs) specific to particular surface antigen. The surviving Giardia (progeny) and clones showed different surface antigens as judged by resistance to cytotoxicity, loss of antigens determined by surface radiolabeling, and failure of MAbs to recognize epitopes by immunoprecipitation. The major varying surface antigens incorporate large amounts of [35S]cysteine compared to [35S]methionine. Surface antigenic variation occurs commonly in Giardia isolates, and the major surface antigens appear to comprise a family of cysteine-rich proteins. PMID- 2911278 TI - Schistosoma mansoni and its intermediate host Biomphalaria glabrata express a common 39 kilodalton acidic protein. AB - Two Schistosoma mansoni proteins of 43 and 39 kDa (Sm43 and Sm39) were shown to react with rabbit antibodies produced against Biomphalaria glabrata proteins. Two dimensional gel electrophoresis of miracidial proteins indicated that Sm43 and Sm39 were acidic proteins (pI 4.8 and 4.9 respectively) and were in vitro translated from miracidial messenger RNA in the same molecular forms. Sm43 and Sm39 were expressed by all parasite stages of S. mansoni. Using anti-Sm43 and anti-Sm39 mouse sera, we demonstrated that both parasite proteins were antigenically related and cross-reacted with a unique 39 kDa (pI 4.9) protein from B. glabrata (Bg39). Cross-reactive components were found in fresh water and land snails but not in vertebrate tissues, suggesting that the 39 kDa protein was specific for invertebrates. PMID- 2911280 TI - Predicted structure of a major Schistosoma mansoni eggshell protein. AB - The complete sequence for a major Schistosome mansoni eggshell protein gene has been determined from a genomic DNA fragment. The use of an open reading frame encoding a glycine-rich polypeptide was confirmed by in vitro translation of schistosome mRNA in the presence of [3H]glycine and comparison with the amino acid composition of purified, schistosome eggshells. Apart from the extraordinary abundance of glycine and tyrosine which are evenly distributed throughout the polypeptide chain, the most striking features of the deduced amino acid sequence are the presence of five well-conserved tandem repeats of 16-18 residues in the N terminal region and the asymmetrical distribution of charged residues. Acidic residues (Asp) are confined to the N-terminal region, while basic residues (Lys, His), with the exception of a single histidine, are found in the C-terminal region. A model structure composed of short anti-parallel beta-strands is proposed, in which glycines and residues with small side chains lie within the strands and tyrosines and cysteines are arranged at the bends, where they would be available for cross-linking. Four such strands form one of the tandem repeats which are predicted in turn to form a stack of five closely packed beta-sheets, each of three strands and linked by the more variable fourth strand. The C terminal region may form a similar but less compact structure. The ordered structure demonstrated by birefringence studies of the schistosome eggshell [Kusel, J. (1970) Parasitology 60, 79-88] could be formed by packing of the polypeptides such that the N-terminal domain contributes counter ions or cross links to the C-terminal domain of adjacent molecules. PMID- 2911279 TI - Qinghaosu does not affect the major thermotropic phase transition in model membranes of dipalmitoylphosphatidylcholine. AB - The effect of the antimalarial agent qinghaosu (artemisinin) on the major thermotropic phase transition in bilayer membranes of dipalmitoylphosphatidylcholine has been studied by differential scanning calorimetry and by the use of fluorescent probes (pyrene excimer formation and depolarization of diphenylhexatriene fluorescence). Addition of up to 40 mol% qinghaosu to dipalmitoylphosphatidylcholine bilayer caused no observable effect on the temperature or enthalpy of the phase transition. The results suggest that the antimalarial action of qinghaosu is not due to a direct effect on the lipid structure of the parasite membrane. PMID- 2911281 TI - Release of the variant surface glycoprotein during differentiation of bloodstream to procyclic forms of Trypanosoma brucei. AB - Investigations on the turnover of the membrane-form variant surface glycoprotein (mfVSG) of Trypanosoma brucei during cultivation in vitro of the monomorphic variant clones MIT at 1.2 and MIT at 1.4 showed that bloodstream forms slowly released the surface coat into the medium (time required to decline to half the initial amount, t50% = 32 +/- 3 h). VSG appeared in the medium in its soluble form (sVSG) which lacked the dimyristoylglycerol membrane anchor as judged by electrophoretic mobility and exposure of the cross-reacting determinant. The total VSG in the culture was very stable with a t50% = 189 +/- 24 h, compared to the other cellular proteins with a t50% approximately 28 h. Coat release during differentiation of bloodstream forms to procyclic cells could be distinguished from this turnover both by its more rapid kinetics (t50% = 13 +/- 1 h) and by the appearance in the medium of a predominant proteolytic fragment in addition to sVSG. Coat release during the transition to procyclic forms was not inhibited by the lysosomotropic agents ammonium chloride or chloroquine, by the proton ionophore monensin, or by the protease inhibitor tosyl-L-lysine chloromethyl ketone. The experiments demonstrate that coat release during differentiation is a specific cellular event distinct from simple turnover. The possibility is discussed that VSG release under both conditions occurs by endocytosis of mfVSG, degradation by a phospholipase C or a protease or both in a non-acidic intracellular compartment and recycling to the surface by exocytosis. PMID- 2911282 TI - A national health program for the United States. A physicians' proposal. AB - Our health care system is failing. Tens of millions of people are uninsured, costs are skyrocketing, and the bureaucracy is expanding. Patchwork reforms succeed only in exchanging old problems for new ones. It is time for basic change in American medicine. We propose a national health program that would (1) fully cover everyone under a single, comprehensive public insurance program; (2) pay hospitals and nursing homes a total (global) annual amount to cover all operating expenses; (3) fund capital costs through separate appropriations; (4) pay for physicians' services and ambulatory services in any of three ways: through fee for-service payments with a simplified fee schedule and mandatory acceptance of the national health program payment as the total payment for a service or procedure (assignment), through global budgets for hospitals and clinics employing salaried physicians, or on a per capita basis (capitation); (5) be funded, at least initially, from the same sources as at present, but with all payments disbursed from a single pool; and (6) contain costs through savings on billing and bureaucracy, improved health planning, and the ability of the national health program, as the single payer for services, to establish overall spending limits. Through this proposal, we hope to provide a pragmatic framework for public debate of fundamental health-policy reform. PMID- 2911283 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 2-1989. A 59-year-old woman with asthma and multiple pulmonary nodules. PMID- 2911284 TI - Universal health insurance: its time has come. PMID- 2911286 TI - Do physicians have an obligation to treat patients with AIDS? PMID- 2911285 TI - Technology and the allocation of resources. PMID- 2911287 TI - Diltiazem and mortality and reinfarction after myocardial infarction. PMID- 2911288 TI - Release of endogenous digitalis-like factor with sodium loading. PMID- 2911289 TI - Treatment of ethylene glycol poisoning with intravenous 4-methylpyrazole. PMID- 2911290 TI - Recognizing the alcoholic patient. PMID- 2911291 TI - Critical care medicine. PMID- 2911292 TI - Teenagers' concerns about nuclear war. PMID- 2911293 TI - Patterns of transmission in measles outbreaks in the United States, 1985-1986. AB - Since the licensing of measles vaccine in 1963, the incidence of reported measles in the United States has declined to less than 2 percent of previous levels. To characterize the current epidemiology of measles in the United States, we analyzed measles outbreaks that occurred during 1985 and 1986. There were 152 outbreaks (defined as five or more cases related epidemiologically), which accounted for 88 percent of the cases reported during those two years. There were two major types of outbreaks: those in which most of the cases occurred among preschool-age children (those under 5 years of age) (26 percent) and those in which most of the cases occurred among school-age persons (those 5 to 19 years of age) (67 percent). The outbreaks among preschool-age children ranged in size from 5 to 945 cases (median, 13); a median of only 14 percent of the cases occurred in vaccinated persons, and a median of 45 percent of the cases were classified as preventable according to the current strategy. Outbreaks among school-age persons ranged in size from 5 to 363 cases (median, 25); a median of 60 percent of the cases occurred in vaccinated persons, and a median of only 27 percent of the cases were preventable. The outbreaks among preschool-age children indicate deficiencies in the implementation of the national measles-elimination strategy. However, the extent of measles transmission among highly vaccinated school-age populations suggests that additional strategies, such as selective or mass revaccination, may be necessary to prevent such outbreaks. PMID- 2911294 TI - Rapid emergence of a focal epidemic of Lyme disease in coastal Massachusetts. AB - We describe a focal epidemic of Lyme disease, which spread from a nature preserve and affected an adjacent community of permanent residents in coastal Massachusetts. The attack rate from 1980 through 1987 was 35 percent among 190 residents living within 5 km of the nature preserve and was greatest (66 percent) among those living closest to the preserve. The risk of infection bore little relation to sex or age. Late Lyme disease, which clustered near the preserve, occurred mainly in residents infected early in the epidemic who did not have a history of erythema migrans and did not receive antibiotic therapy. All the residents with serologic evidence of infection had early or late clinical manifestations of Lyme disease, or both, during the period of study. The seasonal risk of infection was bimodal--greatest in June, with a secondary peak in October -and corresponded to periods of increased transmission. In the nature preserve, the density of the vector tick, Ixodes dammini, exceeded that in other New England sites. The zoonosis rapidly became endemic, and the severity of its impact correlated with the abundance of deer. This epidemic of Lyme disease demonstrated that outbreaks can be focal and can spread rapidly within a community of permanent residents. PMID- 2911295 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 3-1989. A 23-year-old man with recurrent bouts of abdominal pain and vomiting. PMID- 2911296 TI - A closer look at radiocontrast-induced nephropathy. PMID- 2911297 TI - The maturing of geriatrics. PMID- 2911298 TI - HIV infection in sexual partners of HIV-seropositive patients with hemophilia. PMID- 2911299 TI - Increased risk of Lyme disease for cat owners. PMID- 2911300 TI - The pressure to keep prices high at a walk-in clinic. PMID- 2911301 TI - Hired help: a physician's experiences in a for-profit staff-model HMO. PMID- 2911302 TI - Salaried physicians and economic incentives. PMID- 2911303 TI - For-profit medicine: a reassessment. PMID- 2911304 TI - How accurate are hospital scales? PMID- 2911305 TI - Oncologist-induced vomiting: the Igvid syndrome? PMID- 2911306 TI - Nosocomial acquisition of Clostridium difficile infection. AB - We studied the acquisition and transmission of Clostridium difficile infection prospectively on a general medical ward by serially culturing rectal-swab specimens from 428 patients admitted over an 11-month period. Immunoblot typing was used to differentiate individual strains of C. difficile. Seven percent of the patients (29) had positive cultures at admission. Eighty-three (21 percent) of the 399 patients with negative cultures acquired C. difficile during their hospitalizations. Of these patients, 52 (63 percent) remained asymptomatic and 31 (37 percent) had diarrhea; none had colitis. Patient-to-patient transmission of C. difficile was evidenced by time-space clustering of incident cases with identical immunoblot types and by significantly more frequent and earlier acquisition of C. difficile among patients exposed to roommates with positive cultures. Of the hospital personnel caring for patients with positive cultures, 59 percent (20) had positive cultures for C. difficile from their hands. The hospital rooms occupied by symptomatic patients (49 percent) as well as those occupied by asymptomatic patients (29 percent) were frequently contaminated. Eighty-two percent of the infected cohort still had positive cultures at hospital discharge, and such patients were significantly more likely to be discharged to a long-term care facility. We conclude that nosocomial C. difficile infection, which was associated with diarrhea in about one third of cases, is frequently transmitted among hospitalized patients and that the organism is often present on the hands of hospital personnel caring for such patients. Effective preventive measures are needed to reduce nosocomial acquisition of C. difficile. PMID- 2911308 TI - Case records of the Massachusetts General Hospital. Weekly Clinicopathological exercises. Case 4-1989. Sudden onset of abdominal pain and hematemesis in a 56 year-old woman. PMID- 2911307 TI - Use of psychoactive medication and the quality of care in rest homes. Findings and policy implications of a statewide study. AB - Rest homes have become a major component of the health care system for frail elderly persons and deinstitutionalized psychiatric patients. Although psychoactive medications are frequently used in rest homes, there is little detailed information about the extent of such use, its supervision, or its effects. In a survey of a random sample of 55 rest homes in Massachusetts, we found that 55 percent of the residents were taking at least one psychoactive medication. Antipsychotic medications were being administered to 39 percent; of these, 18 percent were receiving two or more such drugs. In a follow-up investigation, we studied 837 residents in 44 rest homes with particularly high levels of antipsychotic-drug use. About half the residents had no evidence of participation by a physician in decisions about their mental health during the year of the study. A third of the residents had performance deficits on mental status testing that indicated serious cognitive impairment, although the causal relation of such impairment to medication use could not be determined. Six percent had evidence of moderate or severe tardive dyskinesia, probably as a side effect of medication. An assessment of staff competence revealed a low level of comprehension of the purpose and side effects of commonly used psychoactive drugs. We conclude that psychoactive drugs are widely used in rest homes, with little medical supervision or understanding by staff members of their possible side effects. PMID- 2911309 TI - Do bacteria cause chronic polyarthritis? PMID- 2911310 TI - Performing arts medicine. PMID- 2911311 TI - What have we learned about the treatment of idiopathic membranous nephropathy with steroids? PMID- 2911312 TI - Acute HIV infection after acupuncture treatments. PMID- 2911313 TI - Transmission of HIV infection from a woman to a man by oral sex. PMID- 2911314 TI - Antibodies to Strongyloides stercoralis in healthy Jamaican carriers of HTLV-1. PMID- 2911315 TI - Lack of antibodies to Borrelia burgdorferi in patients with amyotrophic lateral sclerosis. PMID- 2911316 TI - Retinopathy of prematurity and bilirubin. PMID- 2911317 TI - Immunoreactivity of ceroid lipofuscin storage pigment in Batten disease with monoclonal antibodies to the amyloid beta-protein. PMID- 2911318 TI - Topical administration of 5-aminosalicylic acid: a therapeutic proposal for the treatment of pouchitis. PMID- 2911319 TI - Ciprofloxacin-induced vasculitis. PMID- 2911320 TI - Informed consent in interhospital patient transfer. PMID- 2911321 TI - Association of asthma with serum IgE levels and skin-test reactivity to allergens. AB - We investigated the association of self-reported asthma or allergic rhinitis with serum IgE levels and skin-test reactivity to allergens in 2657 subjects in a general-population study. Regardless of the subjects' status with respect to atopy or their age group, the prevalence of asthma was closely related to the serum IgE level standardized for age and sex (P less than 0.0001), and no asthma was present in the 177 subjects with the lowest IgE levels for their age and sex (greater than 1.46 SD below the mean). The log odds ratio increased linearly with the serum IgE level after we controlled for possible confounders and the degree of reactivity to skin tests. In contrast, allergic rhinitis appeared to be associated primarily with skin-test reactions to common aeroallergens, independently of the serum IgE level. We conclude that asthma is almost always associated with some type of IgE-related reaction and therefore has an allergic basis, although not all the allergic stimuli that cause asthma appear to have been included in the battery of common aeroallergens we used to assess atopic status. These findings challenge the concept that there are basic differences between so-called allergic ("extrinsic") and nonallergic ("intrinsic") forms of asthma. PMID- 2911323 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 5-1989. A 27-year-old Greek woman with portal-vein thrombosis and an epigastric mass. PMID- 2911322 TI - Abnormalities in parathyroid hormone secretion and 1,25-dihydroxyvitamin D3 formation in women with osteoporosis. AB - We investigated the parathyroid hormone-1,25-dihydroxyvitamin D3 (1,25(OH)2D) axis in osteoporosis by administering phosphate to 8 postmenopausal women with osteoporosis (49 to 78 years old) and to 10 normal women matched for age (50 to 74 years). All subjects responded with a similar increase in the serum phosphorus concentration (women with osteoporosis, 1.15 +/- 0.06 to 1.79 +/- 0.09 mmol per liter; controls, 1.14 +/- 0.05 to 1.73 +/- 0.08 mmol per liter) and a fall in the ionized calcium concentration (women with osteoporosis, 1.12 +/- 0.03 to 1.06 +/- 0.03 mmol per liter; controls, 1.17 +/- 0.01 to 1.11 +/- 0.02 mmol per liter). Parathyroid hormone levels rose 2.5-fold in the control group (15.4 +/- 2.2 to 37.9 +/- 6.1 pg per milliliter) but increased by only 43 percent in the group with osteoporosis (14.8 +/- 2.8 to 21.2 +/- 4.1 pg per milliliter), an increase similar to that previously reported in young normal subjects (53 percent). In healthy older and younger subjects, the levels of 1,25(OH)2D did not change; in the subjects with osteoporosis, however, they decreased significantly (50 percent). We conclude that older women require a greater parathyroid hormone stimulus than younger women to maintain vitamin D homeostasis, because of an age related decline in the formation of 1,25(OH)2D in response to parathyroid hormone, and that in osteoporosis the age-appropriate parathyroid hormone response to the same hypocalcemic signal is diminished. Our results are consistent with the presence of an abnormality in parathyroid hormone secretory function in osteoporosis in addition to the universal decline in 1,25(OH)2D responsiveness associated with aging. PMID- 2911324 TI - The regulation of discovery and drug development. PMID- 2911325 TI - The National Leadership Commission's health care plan. PMID- 2911326 TI - Mandatory testing for HIV in federal prisons. PMID- 2911327 TI - Needle-stick injury. PMID- 2911328 TI - Common inheritance of susceptibility to colonic adenomatous polyps and associated colorectal cancers. PMID- 2911329 TI - Microscopic nephrocalcinosis in cystic fibrosis. PMID- 2911330 TI - Diethylcarbamazine and human loiasis. PMID- 2911331 TI - Reliability of home pregnancy-test kits in the hands of laypersons. PMID- 2911332 TI - Making laboratory reports easier to read. PMID- 2911333 TI - Malpractice insurance: caught by the tail. PMID- 2911334 TI - Animal care at Stanford. PMID- 2911335 TI - Paying back student loans. PMID- 2911336 TI - Removing cockroaches from the auditory canal: a direct method. PMID- 2911337 TI - Lamarck, Dr. Steele and plagiarism. PMID- 2911338 TI - UNESCO chemical arms conference opens in Paris. PMID- 2911339 TI - President-elect Bush gets some free advice on science policy. PMID- 2911340 TI - FDA sceptical about link between breast cancer and the pill. PMID- 2911341 TI - More money needed for human genome mapping project. PMID- 2911342 TI - Complacent reviewing. PMID- 2911343 TI - HIV and Kaposi's sarcoma in mice. PMID- 2911344 TI - Parasitology. Seventy-five years of solicitude. PMID- 2911345 TI - Sexual selection. Is bigger always better? PMID- 2911346 TI - Immunology. MHC meets mother's milk. PMID- 2911347 TI - The recent excitement about neural networks. AB - The remarkable properties of some recent computer algorithms for neural networks seemed to promise a fresh approach to understanding the computational properties of the brain. Unfortunately most of these neural nets are unrealistic in important respects. PMID- 2911348 TI - The bicoid protein is a positive regulator of hunchback transcription in the early Drosophila embryo. AB - A gradient in concentration of the protein product of the bicoid gene is a determinant of the anterior-posterior axis of Drosophila embryos. By binding upstream of the segmentation gene hunchback the bicoid protein controls its transcription, thereby translating maternal pattern-generating information into differential activation of zygotic gene expression. PMID- 2911349 TI - Urea excretion as a strategy for survival in a fish living in a very alkaline environment. AB - Ammonia is toxic to all vertebrates. It can be converted to the less toxic urea, but this is a metabolically expensive process found only in terrestrial vertebrates that cannot readily excrete ammonia and marine fish that use urea as an osmotic filler. Freshwater fish mostly excrete ammonia with only a small quantity of urea. It seems the ornithine cycle for urea production has been suppressed in all freshwater teleosts except for some airbreathers which, when exposed to air, increase urea synthesis via the cycle. Here we show that the tilapia fish Oreochromis alcalicus grahami, the only fish living in Lake Magadi, an alkaline soda lake (pH = 9.6-10) in the Kenyan Rift Valley, excretes exclusively urea and has ornithine-urea cycle enzymes in its liver. A closely related species that lives in water at pH 7.1 lacks these enzymes and excretes mainly ammonia with small amounts of urea produced via uricolysis. It dies within 60 min when placed in water from Lake Magadi. We suggest that urea production via the ornithine-urea cycle permits O. a. grahami to survive the very alkaline conditions in Lake Magadi. PMID- 2911350 TI - Female choice selects for a viability-based male trait in pheasants. AB - Recent theory on sexual selection suggests that females in species without paternal care choose mates by their secondary sexual characters because these indicate genotypic quality which will be transmitted to the offspring. These ideas are not yet empirically supported as data quantifying the relationship between female mate choice and female reproductive success are lacking. Only in one case, in Colias butterflies, has it been demonstrated unequivocally that females choose 'good genotypes' as mates and there is only one study, on Drosophila, demonstrating that mate choice increases one component of offspring fitness. Spur length of male pheasants (Phasianus colchicus) correlates with various fitness-related properties. We here present the first experimental field data showing that female pheasants select mates on the basis of male spur length and that female mate choice correlates with female reproductive success. PMID- 2911351 TI - Differential activation of myotube nuclei following exposure to an acetylcholine receptor-inducing factor. AB - A glycoprotein purified from chick brain, of relative molecular mass 42,000, increases the rate of appearance of acetylcholine receptors (AChRs) on the surface of chick myotubes. RNase protection assays have shown that this AChR inducing activity (ARIA) increases the amount of mRNA encoding the alpha-subunit of the AChR, with little or no effect on the amounts of gamma- and delta-mRNAs2. Here, we report that the mRNAs encoding the alpha- and gamma-subunits of the receptor detected by in situ hybridization are concentrated around nuclei in cultured myotubes. Consistent with previous results, ARIA selectively increased the amount of alpha-subunit mRNA, but we now find that all nuclei were not activated to the same extent, with a substantial number not responding at all. Assuming that ARIA is released by motor nerve terminals, our results indicate that only a subset of muscle nuclei are capable of contributing to the accumulation of AChRs at developing neuromuscular junctions. PMID- 2911352 TI - The mucosal vascular addressin is a tissue-specific endothelial cell adhesion molecule for circulating lymphocytes. AB - Tissue position-dependent or address-dependent expression of cell adhesion molecules has been proposed to play a part in cellular positioning in a variety of systems, for example during neural development, the metastasis of neoplasms, and the tissue-specific homing of lymphocytes. The extravasation of blood-borne lymphocytes is regulated by interactions with the endothelium of specialised venules, such as the high endothelial venules (HEV) in organized lymph nodes and mucosal lymphoid tissues. At least three separate lymphocyte-HEV recognition systems have been described, one mediating tissue-selective lymphocyte interactions with HEV in peripheral lymph nodes, another in mucosal lymphoid organs, and a third in inflamed synovium. We have previously identified a tissue specific 'vascular addressin' in the mouse which is selectively expressed by venules mediating lymphocyte-homing into mucosal tissues. To determine whether this addressin is a specific adhesion molecule for lymphocytes, we have isolated it by monoclonal antibody-affinity chromatography and inserted it into supported phospholipid planar membranes. Lymphocytes bind to membranes containing the addressin, but not to phospholipid bilayers or to control glycophorin reconstituted membranes. Only those lymphocytes and lymphoma cell lines capable of binding to mucosal HEV adhere well to the isolated addressin; peripheral lymph node HEV-specific or HEV-non-binding cell lines do not bind. Binding is blocked by anti-addressin antibody MECA-367. We conclude that the mucosal vascular addressin is a tissue-specific endothelial cell-adhesion molecule for lymphocytes, and suggest that it could regulate lymphocyte traffic into mucosal tissues by mediating attachment of blood-borne cells to endothelium. PMID- 2911353 TI - An Fc receptor structurally related to MHC class I antigens. AB - Maternal immunoglobulin G transmitted to the fetus or newborn provides humoral immunity for the first weeks of mammalian life. Fc receptors on intestinal epithelial cells of the neonatal rat (FcRn) mediate the uptake of IgG from milk. Affinity-purified FcRn is resolved by SDS-PAGE into components of relative molecular masses 45,000-53,000 (p51) and about 14,000 (p14). We report the identification of the smaller component as beta 2-microglobulin. Association of beta 2-microglobulin with p51 was confirmed by crosslinking in intestinal epithelial cell brush borders. We have cloned a cDNA encoding the presumptive Fc binding subunit, p51, and its predicted primary structure has three extracellular domains and a transmembrane region which are all homologous to the corresponding domains of class I major histocompatibility complex (MHC) antigens. This is the first time a function has been assigned to an MHC antigen-related molecule. PMID- 2911355 TI - AAU issues guidelines on dealing with scientific fraud. PMID- 2911354 TI - Coexistence of A- and B-form DNA in a single crystal lattice. AB - It is well known that DNA can exist in a variety of conformations which can be interconverted by relatively mild changes in conditions. The in vivo conformation of DNA is usually thought to be the B form, but there is recent evidence that other conformations may be important in DNA-protein recognition. Different fragments of DNA crystallized under virtually identical conditions can form A, B or Z helices. A fragment that adopted an A conformation in a crystal was found in the B conformation in solution, whereas NMR spectroscopy of A-DNA films revealed the presence of a substantial amount of disordered B-DNA. Until now, however, a DNA fragment of a given sequence has not been crystallized in more than one global conformation. We report here an X-ray diffraction study of crystals of the DNA octamer dGGBrUABrUACC. In addition to a 'framework' of A-DNA, which gives discrete X-ray reflections, there are partially disordered B-DNA helices, recognized by their diffuse scattering features. PMID- 2911356 TI - Indo-French agreement stresses vaccines. PMID- 2911357 TI - Anonymous peer refereeing. PMID- 2911358 TI - Polyhedra for helical proteins. PMID- 2911359 TI - Gene transcription. Waves of DNA supercoiling. PMID- 2911360 TI - Vertebrate neurobiology. Sound localization mechanisms. PMID- 2911361 TI - History revealed from bones. PMID- 2911362 TI - Circadian rhythms: mutant hamster in a hurry. PMID- 2911363 TI - Dominance of South American marsupials. PMID- 2911364 TI - Selective action of artificial membranes. PMID- 2911365 TI - Fitness costs of gestation and lactation in wild mammals. AB - Like a number of plants, some mammals commonly produce more progeny than they can afford to rear, terminating investment in some or even all of their offspring once the resources available for breeding are known. Adaptive interpretations of juvenile wastage rely on the argument that the costs of gestation are small compared to those of feeding offspring. Though energetic evidence supports this conclusion, it is unsafe to assume that the relative costs of gestation and lactation to the mother's survival and future reproductive success follow the same pattern because lactation commonly coincides with the period of maximum food availability. Controlling for individual variation, we show that in wild red deer (Cervus elaphus L) any costs of gestation to the mother's subsequent survival and reproductive success are slight compared to those of lactation. PMID- 2911366 TI - The potential role of pathogens in biological control. AB - It is now well established that pathogens such as viruses, fungi bacteria and protozoans can have profound effects on the dynamics of their invertebrate host populations. Theoretical models of invertebrate host-pathogen interactions which assume uniform structure of the pathogen population may reasonably explain the oscillatory behaviour observed in some systems, but do not adequately describe the existence of more constant populations found in other host-pathogen interactions. An examination of the literature relating to these relatively stable systems suggests that the common thread is the eventual transmission of some of the more protected, longer-lived stages of the pathogen occurring in reservoirs, such as the soil, host cadavers on trees, or the live host itself. In this letter, I propose a new theoretical model which incorporates this population structure and accounts for the range of dynamics observed in natural systems. In particular, I show that host populations may be regulated to low and relatively constant densities if sufficient numbers of pathogens are trans-located from pathogen reservoirs to habitats where transmission can occur. An understanding of pathogen reservoirs may be of value in the design of biological control programmes and may greatly increase the effectiveness of pathogens as biological control agents. PMID- 2911367 TI - Induction of endogenous IFN-alpha and IFN-beta genes by a regulatory transcription factor, IRF-1. AB - Interferons (IFNs) have an important role in cell growth and differentiation. The most well-known function of IFNs is their antiviral activity; viral infections result in induction of the transcription of the IFN-alpha and IFN-beta genes. Recently we isolated the gene encoding a transcription factor, IRF-1, that may play a part in the induction of IFN genes. Interestingly, the IRF-1 gene itself is virus-inducible, suggesting the importance of de novo production of IRF-1 in IFN gene induction. Here we show that high-level expression of the cloned mouse IRF-1 gene in monkey COS cells results in the induction of endogenous IFN-alpha and IFN-beta genes without viral stimulation. Furthermore, we demonstrate the induction of these genes by an IRF-1/yeast GAL4 chimaeric transcription factor. This may be the first demonstration of the specific induction of silent chromosomal genes by transfection of a single transcription factor gene in mammalian cells. PMID- 2911368 TI - Identification of specific binding proteins for a nuclear location sequence. AB - The nuclear envelope is a selective barrier against the movement of macromolecules between the nucleus and cytoplasm. Nuclear proteins larger than relative molecular mass 20,000-40,000 are probably actively transported across the envelope through the nuclear pore complex and are directed by specific nuclear location sequences (NLS) in the proteins. NLS mediate the nuclear import of isolated nuclear proteins after microinjection into whole cells and the nuclear accumulation of chimaeric proteins or of non-nuclear proteins conjugated to synthetic peptides. The best-characterized NLS is the simian virus 40 large T antigen sequence. We have identified two proteins of rat liver by chemical cross linking that interact with a synthetic peptide containing this sequence: this interaction is specific for a functional NLS, is saturable, and high affinity. The binding proteins are present in a post-mitochondrial supernatant, in nuclei and in a nuclear envelope fraction, which is consistent with a role in the transport of nuclear proteins from the cytoplasm to the nucleus. PMID- 2911369 TI - Mutation rates differ among regions of the mammalian genome. AB - In the traditional view of molecular evolution, the rate of point mutation is uniform over the genome of an organism and variation in the rate of nucleotide substitution among DNA regions reflects differential selective constraints. Here we provide evidence for significant variation in mutation rate among regions in the mammalian genome. We show first that substitutions at silent (degenerate) sites in protein-coding genes in mammals seem to be effectively neutral (or nearly so) as they do not occur significantly less frequently than substitutions in pseudogenes. We then show that the rate of silent substitution varies among genes and is correlated with the base composition of genes and their flanking DNA. This implies that the variation in both silent substitution rate and base composition can be attributed to systematic differences in the rate and pattern of mutation over regions of the genome. We propose that the differences arise because mutation patterns vary with the timing of replication of different chromosomal regions in the germline. This hypothesis can account for both the origin of isochores in mammalian genomes and the observation that silent nucleotide substitutions in different mammalian genes do not have the same molecular clock. PMID- 2911370 TI - Soviet nuclear dissent. PMID- 2911371 TI - More criticism for NIH over 'summary' cut of grants. PMID- 2911372 TI - NIH gives the go-ahead on genetic experiment. PMID- 2911373 TI - Vet schools to close. PMID- 2911374 TI - Guidelines produced for the use of transgenic animals in research. PMID- 2911375 TI - HIV a problem for Indian blood banks. PMID- 2911376 TI - Testing of in vitro embryos approved. PMID- 2911377 TI - Another blow for creationism in California. PMID- 2911378 TI - AIDS test law. PMID- 2911379 TI - Lessons from eugenic history. PMID- 2911380 TI - Suffer the animals. PMID- 2911381 TI - What, if anything, is Prochloron? PMID- 2911382 TI - Moving in on plant genes. PMID- 2911383 TI - Setting radiation standards. PMID- 2911384 TI - X-chromosome reactivation and ageing. PMID- 2911385 TI - Misidentified cell. PMID- 2911386 TI - A mutation that changes cell movement and cell fate in the zebrafish embryo. AB - The study of developmental patterning has been facilitated by the availability of mutations that produce changes in cell fate, in animals such as Caenorhabditis elegans and Drosophila melanogaster. We now describe a zygotic lethal mutation in the zebrafish, Brachydanio rerio, that also changes how particular embryonic cells develop. Severe pattern deficiencies are observed that are restricted to a single body region, the trunk. The mutation may directly affect mesoderm, as somites do not form in the trunk. Head and tail structures, including tail somites, are relatively undisturbed. The earliest detected expression of the mutation is during gastrulation, when movements of mesodermal cells occur incorrectly. We injected prospective trunk mesodermal cells with lineage tracer dye and observed that in mutants these cells may enter a new body region, the tail, and there may express a new fate appropriate for the changed position. PMID- 2911387 TI - Nerve growth factor regulates expression of neuropeptide genes in adult sensory neurons. AB - Nerve growth factor (NGF) is a trophic molecule essential for the survival of sympathetic and sensory neurons during ontogeny. The extent to which NGF is involved in the maintenance or regulation of the differentiated phenotypes of mature peripheral neurons is much less clear, however. Biochemical analysis of the actions of NGF upon peripheral neurons has been hampered by the lack of a preparation of neuronal cells that are responsive to NGF but do not require it for survival. We report here that in adult dorsal root ganglion neurons, which can be isolated, enriched and maintained in culture in the absence of neuronal growth factors, the expression of mRNAs encoding the precursors of two neuropeptides, substance P and calcitonin gene-related peptide is regulated by NGF. Our results provide the first direct evidence of a continuous dynamic role for NGF in regulation of peptide neurotransmitter/neuromodulator levels in mature sensory neurons. PMID- 2911388 TI - Genetically haploid spermatids are phenotypically diploid. AB - Because chromosomal homologues segregate from one another during meiosis, spermatids are genetically different. Post-meiotic gene expression could lead to gametic differences, some of which might lead to preferential transmission of certain alleles over others. In both insects and mammals, however, all the cells derived from a single spermatogonial cell develop within a common syncytium formed as a result of incomplete cytokinesis at each of the mitotic and meiotic cell divisions. It has been proposed that the intercellular bridges connecting the cells, which are about 1 micron in diameter, permit the sharing of cytoplasmic constituents, thus ensuring the synchronous development of a clone of cells and gametic equivalence between haploid spermatids. By analysing the product of a transgene which is expressed exclusively in post-meiotic germ cells in hemizygous transgenic mice, we have shown that genetically distinct spermatids share the product of the transgene and hence can be phenotypically equivalent. PMID- 2911389 TI - The relationship of a prochlorophyte Prochlorothrix hollandica to green chloroplasts. AB - It is generally accepted that chloroplasts arose from one or more endosymbiotic events between an ancestral cyanobacterium and a eukaryote. Such an origin fits well in the case of the chloroplasts of rhodophytes that, like cyanobacteria, contain chlorophyll a and phycobilin pigments. The green chloroplasts from higher plants, green algae, and euglenoids however, contain chlorophyll b as well as chlorophyll a, and lack phycobilins. Consequently, it has been suggested that they arose independently of the rhodophyte chloroplasts, from an ancestral prokaryote containing that complement of pigments. The 'prochlorophytes' Prochloron didemni (an exosymbiont on didemnid ascidians) and Prochlorothrix hollandica (a recently discovered, free-living, filamentous form) have been suggested to be modern counterparts of the ancestor of the green chloroplasts because they are prokaryotes that also contain both chlorophylls a and b, and lack phycobilins. We report here a 16S rRNA-based phylogenetic analysis of P. hollandica. The organism is found to fall within the cyanobacterial line of descent, as do the green chloroplasts, but it is not a specific relative of green chloroplasts. Thus, similar pigment compositions do not necessarily reflect close evolutionary relationships. PMID- 2911390 TI - Declining trends in mortality from cerebrovascular disease at ages 10-65 years: a test of validity. AB - Recent reports of declining trends in mortality rates from cerebrovascular disease are based on underlying cause of death as stated on the death certificate, and may contain inaccuracies because death certificates are often completed without reference to all information in medical records, and because of changes in coding conventions and diagnostic fashion. This is a report of trends in mortality rates from cerebrovascular disease in Baltimore, Md., during 1950 1970 using data validated by reference to individual medical records from 19 hospitals. Overall accuracy of death certificate diagnoses did not change markedly during the study period. Death rates from subarachnoid hemorrhage increased in white women, but decreased in white men and in nonwhites of both sexes. Death rates from other cerebrovascular diseases declined in most sex and color groups, a result which cannot be attributed to errors in death certificate diagnoses. The increasing rates of subarachnoid hemorrhage observed in white women deserve further attention. PMID- 2911391 TI - Conditions associated at death with specific types of completed stroke in patients with and without hypertension: a case-control study. AB - Potential risk factors for various types of stroke were studied using a case control study design. All 1978 US death certificates for which the registered underlying cause of death was subarachnoid hemorrhage (SAH), cerebral hemorrhage (CH), or cerebral infarction (CI) were identified. The frequency with which other conditions appeared on the death certificates of cases with and without hypertension was compared with controls. These data provide new information, such as the occurrence of peripheral vascular disease in association with SAH, the risk of CH in epileptic and cirrhotic patients, and the association of benign neoplasms of the nervous system, motor neuron disease, and 'paralysis agitans' with CI. PMID- 2911392 TI - Risk of multiple sclerosis in relation to industrial activities: an ecological study in four European countries. AB - The pattern of industries, in terms of workers in any individual industry in relation to total population, was compared with multiple sclerosis (MS) risk, as reported in previous communications in Norway, Denmark, Sweden and Switzerland. A great number of correlations with MS was found but, when intercorrelations were considered, paper manufacturing appeared to be the most closely associated with MS. The possible relevance of these findings in view of the methodological limitations is discussed. PMID- 2911393 TI - Descriptive epidemiologic survey of head injury in the Army: 1983 hospitalized cases. AB - A descriptive epidemiologic study of head injury cases that were discharged from army medical facilities during fiscal year 1983 was performed. For the diagnosis of concussion, the male and female rates were approximately equal between the ages 18-24 and 25-34 and for the total, ages 18-34. For the diagnosis of other intracranial injury and the total of all head injuries, males between ages 18-24 and 18-34 had statistically significantly higher rates than females. Cases were reviewed from Walter Reed Army Medical Center to test the hypothesis that alcohol and drug abuse were underreported risk factors for military personnel sustaining head injuries. PMID- 2911394 TI - Jugular vein distension: trouble in the heart's right side. PMID- 2911395 TI - Emergency interventions. PMID- 2911397 TI - A faith that moved hands. PMID- 2911398 TI - Maintaining a nasogastric tube. PMID- 2911399 TI - Of lullabies--and lifelines. PMID- 2911400 TI - Ciprofloxacin and norfloxacin--potent oral antiinfectives. PMID- 2911401 TI - Where you stand in the eyes of the law (continuing education credit). PMID- 2911402 TI - Remembering Danny. PMID- 2911403 TI - Dealing with serious depression in cancer patients. PMID- 2911404 TI - Performing CPR on children. PMID- 2911405 TI - Cocaine--the deadliest addiction. PMID- 2911406 TI - Discharge planning: the sooner, the better. PMID- 2911408 TI - Out of uniform. PMID- 2911407 TI - Insights on death & dying. PMID- 2911409 TI - Rush to judgment. PMID- 2911410 TI - Myths & facts about i.v. therapy. PMID- 2911411 TI - Think twice about sensory loss. PMID- 2911412 TI - Power in nursing: images and reality. Interview by Lyndon Keene. PMID- 2911413 TI - Single registration: NZNA's view. PMID- 2911415 TI - Financial planning for women. PMID- 2911414 TI - Individual employment contracts: beware. PMID- 2911416 TI - Killing the habit. PMID- 2911417 TI - Dying with dignity. PMID- 2911418 TI - Working for workers' health. PMID- 2911419 TI - Cocaine abuse during pregnancy: maternal and fetal implications. AB - Cocaine abuse during pregnancy has been reported to be associated with a variety of fetal complications and with preterm labor. In this cohort study, pregnancy outcome and health status of infants born to 53 cocaine abusers were compared with those of another group of 100 unexposed women and their infants. Significantly more (P less than .05) pregnancies of abusers were associated with preterm labor. In addition, significantly more (P less than .05) infants had complications at birth (ie, meconium, tachycardia). Infants born to cocaine abusers also had significantly lower (P less than .05) birth weight than infants of controls, and an excess of congenital cardiac anomalies (P less than .01). PMID- 2911420 TI - Twice a cesarean, always a cesarean? AB - The cesarean delivery rate has quadrupled during the past two decades, resulting in considerable attention focused on alternatives to cesarean birth. One option, vaginal birth after one previous cesarean, has come to be recognized as an acceptable alternative to routine elective repeat cesarean delivery. The purpose of this report was to evaluate whether women with two previous cesareans can safely undergo a trial of labor. Between July 1, 1982 and June 30, 1986, data were collected prospectively on all women with previous cesareans. Those with a known classical incision or a medical or obstetric contraindication to a trial of labor were excluded from an attempted vaginal delivery. During this period, 67,784 patients were delivered, of whom 6250 (9.2%) had had a previous cesarean. Of the 6250 previous-cesarean patients, 1088 (17.4%) had had two previous cesareans; of these, 501 (46%) underwent a trial of labor and 346 (69%) delivered vaginally. Whereas the overall rate of uterine dehiscence was 3%, the rate in those women who attempted a vaginal delivery was 1.8%, versus 4.6% in those who did not. Overall, oxytocin was used in 284 (57%) and was associated with a dehiscence rate of 2.1%, versus 1.4% in the no-oxytocin group. Successful vaginal delivery was related significantly to the use of oxytocin and to a previous vaginal delivery. Trial of labor in patients with two previous cesareans appears to be a reasonable consideration. PMID- 2911421 TI - Changes in the pattern of uterine contractility in relationship to coitus during pregnancies at low and high risk for preterm labor. AB - This is a preliminary, prospective study of uterine contractility in response to sexual intercourse. The study population consisted of 30 pregnant subjects. Group I included 15 women treated for an episode of preterm labor with intravenous and oral tocolysis in this pregnancy, and group II was a matched control group of low risk volunteers. The availability of home uterine tocodynamometric systems permitted monitoring of uterine contractility for three 60-minute time periods related to coitus. A significant increase in uterine contractility in the immediate postcoital period was observed for the high-risk women, but not for the controls. This increased uterine activity subsided spontaneously within 2-3 hours, returning to baseline. These initial preliminary observations of uterine response to coitus in a home environment are interesting; however, further research is suggested to establish their clinical implications. PMID- 2911422 TI - Erythrocyte and plasma magnesium during teenage pregnancy: relationship with blood pressure and pregnancy-induced hypertension. AB - A prospective study of 53 nulliparous teenagers was conducted to determine differences in erythrocyte and plasma magnesium concentrations between subjects who had normal full-term deliveries (normal pregnant group) and those who developed pregnancy-induced hypertension. Magnesium content of monthly blood samples was determined by atomic absorption spectrophotometry. Socioeconomic data and information on use of supplements, medicines, tobacco, and alcohol were obtained by interview and medical chart review. Erythrocyte magnesium levels in both groups remained stable during pregnancy, whereas plasma magnesium showed a slight decline (P less than .08). Plasma and erythrocyte magnesium did not differ significantly between the normal pregnant (N = 30) and pregnancy-induced hypertension (N = 12) groups. Overall, mean arterial pressure was not significantly related to plasma or erythrocyte magnesium values. Within the pregnancy-induced hypertension group, there was a slight (P less than .05) inverse relationship between mean arterial pressure and plasma magnesium. The two groups were similar for socioeconomic characteristics, gynecologic age, previous use of oral contraceptives, and use of tobacco and magnesium-containing supplements. Pregnancy-induced hypertension subjects reported more alcohol use than did normal pregnant subjects (P less than .02). In conclusion, there was no evidence of magnesium depletion among teens who developed pregnancy-induced hypertension, by measurement of erythrocyte or plasma magnesium. PMID- 2911423 TI - Meconium in the amniotic fluid and fetal acid-base status. AB - Of 323 pregnancies with meconium-stained amniotic fluid at 36-42 weeks' gestation, 68 (21%) had a pH less than 7.20 in umbilical arterial blood, 21 (7%) had a pH less than 7.15, and only three newborns (0.9%) had true metabolic acidemia. At birth, of the 74 newborns with normal electronic fetal heart rate (FHR) tracings, eight (11%) had an umbilical arterial pH less than 7.20. There was a significantly higher frequency of acidemia (defined as pH less than 7.20) in newborns with both baseline and periodic FHR abnormalities. Although there was a significant difference (P less than .05) in the frequency of meconium found below the cords in these neonates with an umbilical artery pH less than 7.20 compared with those with values exceeding 7.20, there was no significant difference in the frequency of clinical meconium aspiration syndrome. We conclude that meconium-stained amniotic fluid correlates poorly with infant condition at birth as reflected by umbilical cord acid-base measurements. PMID- 2911424 TI - Umbilical cord blood serosurvey for human immunodeficiency virus in parturient women in a voluntary hospital in New York City. AB - The potential spread of the human immunodeficiency virus (HIV) to childbearing women in areas of high acquired immunodeficiency syndrome (AIDS) endemicity is a major public health concern. As a private institution providing obstetric care to such a population of women, we undertook an anonymous HIV cord blood serosurvey to estimate the number of childbearing women at our institution at risk for perinatal transmission of the virus and to assess the success of our voluntary screening program to identify seropositive women. Between November 1987 and January 1988, cord blood samples from all clinic deliveries were analyzed for the presence of HIV antibody. For each sample obtained, the mother's age and site of prenatal care were known. Overall, 2.7% (six of 224) of the samples tested were seropositive; two of the 34 samples (5.9%) from teenage mothers were seropositive. All positive samples were from women who received prenatal care; none were identified through a voluntary screening program based on patient self acknowledged risk-behavior assessment. This confirms that risk factor history elicited by personal interview is not a reliable screening tool for initiating HIV antibody counseling and testing. The high seropositive rate in teenagers is disturbing and needs further assessment. PMID- 2911425 TI - Evaluation of maternal perception of sound-provoked fetal movement as a test of antenatal fetal health. AB - Maternal perception of sound-provoked fetal movement was correlated with the results of nonstress cardiotocography in 1097 women with obstetric or medical antenatal risk factors. Ninety-two percent of the mothers felt fetal movements with the stimulus; all but three had a reactive non-stress test (NST). These three women were taking multiple antihypertensive drugs and were less than 33 weeks' gestation. Of 88 patients with no maternal perception of sound-provoked fetal movement, ten had nonreactive NSTs. Ultrasound confirmed the absence of fetal movement to the stimulus. The outcome in nine of these ten cases suggested some evidence of fetal compromise. Maternal perception of sound-provoked fetal movement correlated well with the results of the NST; the sensitivity (76.9%), specificity (92.8%), and negative predictive value (99.7%) were all high, although the positive predictive value was only 11.4%. Maternal perception of sound-provoked fetal movement may suffice as an inexpensive and simple method of evaluating antenatal fetal well-being in risk situations. When the mother is doubtful or does not feel the sound-provoked fetal movement, NST is indicated to evaluate the fetal health. PMID- 2911426 TI - Atypical luteinizing hormone rise and associated fertilization failure in non male factor in vitro fertilization patients. AB - The purpose of this investigation was to analyze fertilization failure in non male factor infertility in vitro fertilization (IVF) patients. Twenty-five nonfertilized IVF patients were compared with 57 successfully fertilized IVF patients. Patients were matched for age, ovulation-induction protocol, and cycle. The two groups were similar with respect to infertility etiology, peak estradiol, and total oocytes retrieved at laparoscopy. There was a greater incidence of primary infertility (64 versus 49%) and mean years of infertility (5.4 +/- 0.4 versus 4.6 +/- 0.3) in the nonfertilization group, although these differences were not statistically significant. Most important, the nonfertilization patients had a greater incidence of an atypical LH rise prior to hCG administration (60 versus 18%; P less than .001) and fewer mature oocytes (2.0 +/- 0.3 verus 3.4 +/- 0.3; P less than .01). Stepwise linear regression analysis yielded four primary factors for predicting fertilization failure: infertility duration, primary infertility, number of mature oocytes, and presence of LH rise. These findings help characterize several potential factors other than oligozoospermia that are associated with nonfertilization, and support LH monitoring in IVF and gamete intrafallopian tube transport patients. PMID- 2911427 TI - Hysteroscopic metroplasty: six years' experience. AB - Seventy patients who underwent hysteroscopic metroplasty for uterine septa during a 6-year period were reviewed for subsequent gynecologic problems and obstetric outcome. Complete follow-up was obtained for 1 year in 60 patients and through the first pregnancy in 64. The 70 patients were divided into three groups based on obstetric history prior to surgery: 1) 40 with only first-trimester losses, 2) 15 whose histories included second-trimester losses or premature delivery, and 3) 15 with primary infertility. Long-term follow-up indicated no significant gynecologic abnormalities. Comparison of preoperative and postoperative obstetric outcomes indicated the following: 1) Hysteroscopic metroplasty was very effective in treating patients with septa and a history of first-trimester abortion; 2) patients with first-trimester loss and either second-trimester abortion or preterm birth benefited from metroplasty but were still at risk for preterm labor; and 3) hysteroscopic metroplasty does not "cure" unexplained infertility. When compared with abdominal metroplasty for efficacy, morbidity, and cost, hysteroscopic metroplasty appears to be the treatment of choice in patients with uterine septa associated with pregnancy loss. Those patients with a history of second-trimester loss and third-trimester preterm delivery continue to require close monitoring in subsequent pregnancies. PMID- 2911428 TI - Ectopic pregnancy and recurrent spontaneous abortion: two associated reproductive failures. AB - The association between spontaneous abortion and ectopic pregnancy was evaluated in a case-control study conducted on 161 women (cases) with recurrent spontaneous abortions (two or more consecutive spontaneous abortions) and 170 control subjects who delivered normal infants. The risk of ectopic pregnancy in women with a history of recurrent spontaneous abortion was about fourfold that of controls (relative risk adjusted for age and number of pregnancies = 4.3; 95% confidence interval 1.4-14.7). This association was confirmed by comparing the observed number of extrauterine pregnancies in women with recurrent spontaneous abortions with the expected number computed from regional data on the frequency of ectopic pregnancies; the estimated relative risk was 3.7, with a 95% confidence interval of 2.2-7.0. The present report found an association between spontaneous abortions and ectopic pregnancies, suggesting some common risk/etiologic factors for these two reproductive failures. PMID- 2911429 TI - Pathologic aspects of the umbilical cord after percutaneous umbilical blood sampling. AB - Percutaneous umbilical blood sampling (cordocentesis) appears to be a valuable new procedure for prenatal diagnosis. In order to evaluate whether focal injury of the umbilical vessels caused by the needle puncture is potentially harmful, we completely examined 50 umbilical cords collected between 1 hour and 20 weeks after cordocentesis. Macroscopic evidence of the needle entry was found in 37 cases, including one giant hematoma of the cord. Within 48 hours after the procedure, microscopic examination of transverse sections taken at the puncture site revealed distinct perforation of the vessel wall, associated in four cases with a small hematoma encircling the vessel. One week after cordocentesis, the vessel wall was partially reformed. There were no histologic differences between needle entry in a vein or in an artery. No thromboses of the umbilical vessels were found. PMID- 2911430 TI - The acute effect of cordocentesis with or without fetal curarization and of intravascular transfusion upon umbilical artery waveform indices. AB - The systolic/end-diastolic ratio (S/D) and pulsatility and resistance indices were calculated before and after diagnostic cordocentesis in 46 fetuses, after 19 intravascular transfusions in eight fetuses, and on two occasions 45 minutes apart in eight controls. The fetus was paralyzed with pancuronium (0.3 mg/kg sonographic estimate of fetal weight) for diagnostic cordocentesis on 19 occasions (intravascularly in 17 and intramuscularly [IM] in two). Pancuronium (intravascularly in 16; IM in three) and furosemide (4 mg/kg intravenously) were administered during each transfusion. There were no significant differences between the first and second measurements for any of the three indices in the control group. Significant reductions were documented in the S/D ratio (P less than .0001), the pulsatility index (P = .043), and the resistance index (P less than .0001) after diagnostic cordocentesis. Pancuronium administration did not alter the magnitude of the decline, nor was there an association between the decline and the volume of blood removed. Significant relationships were observed between the magnitude of the decline and several respiratory blood gas measurements. As in the diagnostic cordocentesis group, there were significant reductions in each Doppler index after transfusion (S/D ratio, P = .003; pulsatility index, P = .002; resistance index, P = .0001). In addition, there was a significant relationship between gestational age and S/D ratio (r = 0.70, P = .002) in fetuses undergoing intravascular transfusion. The S/D ratio was most sensitive to changes in fetal oxygenation. We conclude that both diagnostic cordocentesis and intravascular transfusion as performed at the University of Iowa acutely lower the studied Doppler waveform indices. PMID- 2911431 TI - "Madame A is a 30-year-old housewife, gravida X, para Y ...". PMID- 2911432 TI - Fine-needle aspiration of inguinal lymph nodes in gynecologic practice. AB - Palpable inguinal lymph nodes are a common finding in gynecologic patients. Assessment of such nodes is especially important in the clinical staging of pelvic cancers. To determine the accuracy, safety, and usefulness of fine-needle aspiration in this setting, we retrospectively reviewed pathologic and clinical data from 62 consecutive aspirates of inguinal lymph nodes in 48 gynecologic patients, of whom 42 had cancer. Aspirates from 37 patients yielded diagnostic material. Aspirated tumor cells consistently reflected the primary tumor histology. Tumors included carcinomas of the vulva, vagina, and cervix, and carcinomas and mixed mesodermal cancers of the corpus and ovary. Node excision and clinical observations provided adequate follow-up for 19 positive and 15 negative aspirates, and identified no false positives and two false negatives. The role of fine-needle aspiration varied with the tumor type and stage. It provided the first microscopic diagnosis of cancer in six patients and the first diagnosis of metastasis in six others. Decisions concerning surgery, radiation ports, and chemotherapy frequently depended on the results of fine-needle aspiration. There were no complications from the procedure. Fine-needle aspiration is an accurate, safe, and useful method for assessing clinically suspicious inguinal nodes. PMID- 2911433 TI - Pleuroamniotic shunting for decompression of fetal pleural effusions. PMID- 2911435 TI - The intrauterine device and pelvic inflammatory disease revisited: new results from the Women's Health Study. PMID- 2911434 TI - Birth asphyxia: does the Apgar score have diagnostic value? PMID- 2911436 TI - Fetal choroid plexus cysts. PMID- 2911437 TI - Comparison of image layer location among panoramic machines of the same manufacturer. AB - The central plane of the image layer was located in several panoramic machines of the same manufacturer by making radiographs of a spherical test object placed in different positions. A round image indicated that the test object was at the central plane. The inconsistency of the location of the central plane in machines tested indicates the need for establishing a quality assurance test to verify image-layer location before patient exposure. PMID- 2911438 TI - The effect of patient movement on resolution. AB - The effect of long exposure time on patient movement and resulting radiographic resolution was simulated and then measured by visual-light photographic techniques for four radiographic projections. A mathematic relation was then derived to transform these measurements to the maximum resolutions that could have been obtained with radiographs under similar conditions. The results indicate that radiographs of rigid structures such as bones and teeth can be taken with reasonable resolution at exposure times much longer than normally used in clinical practice. It was also found that radiographs taken with the film rigidly fixed to the object being studied will exhibit remarkably less blurring from patient motion than radiographs taken when the patient and the film are not coupled. In addition it was found that motion artifacts are reduced to a minimum when the plane of the film is perpendicular to the radiation beam. PMID- 2911439 TI - A classification of temporomandibular joint disk morphology. AB - Disk morphology has been recognized as an important feature of internal derangements of the temporomandibular joint and as a suspect in functional impediments. A classification of disk shapes was devised by means of corrected lateral cephalometric arthrotomograms and histopathologic sagittal sections. Five basic shapes were identified: bow tie (normal), straight, funnel, bulge, and Y. Statistical analyses were performed. The normal condyle-disk-fossa relationship and slight-to-moderate disk displacement occurred with disk shape 1 (bow tie). Severe disk displacement without reduction occurred predominantly with disk shape 4 (bulge). Beaking of dye in the anterior recess of the inferior joint space was an indicator of abnormal disk morphology and displacement. PMID- 2911441 TI - Treatment of severe microstomia caused by swallowing of caustic soda. AB - Treatment of severe microstomia caused by swallowing of caustic soda is presented. The oral cavity was severely constricted because of mucosal adhesions. We used a free forearm flap for reconstruction of the oral cavity and vermilion flaps at the oral commissure, with satisfactory results. A technique is presented, and the problems with respect to the reconstruction of the oral cavity are discussed. PMID- 2911442 TI - Technical improvements in the sagittal split ramus osteotomy. AB - This article addresses the potential sources of morbidity associated with the sagittal split ramus osteotomy. Refinements in the instrumentation and technique are described; these enhance the exactness of the procedure, thereby minimizing the complications and improving the stability of the surgical result. PMID- 2911440 TI - Long-term follow-up after occlusal treatment to correct abnormal temporomandibular joint disk position. AB - Fifteen patients with temporomandibular joint disk displacement in whom a normal condyle-disk relationship could be established were treated with occlusal changes to maintain the disk in a recaptured position. Occlusal changes were achieved by prosthodontics in 11 patients and by orthodontics in four patients. Follow-up after about 3 years showed that joint function was improved, intensity of pain was reduced, and joint and muscle tenderness were less frequent than before treatment. Intermittent locking, use of analgesics, sleep disturbances, and absence from work because of temporomandibular joint symptoms were also less frequent. Radiographic examination performed in 11 patients at follow-up demonstrated anteroinferior condylar position in the majority of the patients, but only minor hard tissue changes. Arthrography showed the disk to be in a correct position relative to the condyle in 82% (9 of 11) of the patients. These results suggest that permanent change of the occlusion with the objective of eliminating abnormal disk position may be effective treatment for disk displacement when conventional methods of treatment have failed to alleviate the symptoms. The extent of dental treatment needed to maintain the disk in a correct position should, however, be considered relative to the severity of the symptoms. PMID- 2911443 TI - An interesting condylar fracture revealed by use of computed tomography. A case report. PMID- 2911444 TI - Oral erythema multiforme: clinical observations and treatment of 95 patients. AB - Erythema multiforme is a chronic, inflammatory mucocutaneous disease that can occur in both genders at any age. Although the cause remains obscure, a wide range of antigens and factors, including herpesvirus and other infections, has been suggested as triggering the disease. In the present study of 95 patients, we found that patients with oral involvement alone tend to predominate over those who have oral and lip, or oral, lip, and skin disease. There were also more women than men. Our study further confirmed that erythema multiforme cannot be characterized solely as a disease that is cyclical and self-limiting. The dramatic response to corticosteroids and to the immunoregulating agent levamisole, as well as the fact that patients with erythema multiforme are otherwise essentially healthy, suggests that erythema multiforme may be caused by a transient autoimmune defect, possibly triggered by multiple factors. Because 19 patients with oral candidiasis responded to antifungal therapy, a possible antigenic role for these organisms is suggested. PMID- 2911445 TI - Cross-infection control: attitudes of patients toward the wearing of gloves and masks by dentists in the United Kingdom in 1987. AB - Dental patients in the United Kingdom were surveyed in February 1987 with respect to their views on whether dentists should wear gloves and/or masks. Most patients believed that gloves should be worn and few saw no need for either. Patients receiving care in a dental hospital were more enthusiastic than those seen in general practice in the belief that dentists should wear gloves and/or a mask. PMID- 2911446 TI - Spindle and epithelioid cell nevus of tongue at an unusual site. AB - A case of spindle and epithelioid cell nevus of the tongue is presented. It shows unusual and distinctive desmoplasia and cells containing melanosomes identified by histochemical and electron microscopic techniques. We believe this is the second case, but the first fully documented report, of this unusual nevus of tongue reported in the literature. PMID- 2911447 TI - Chronic pulmonary histoplasmosis with an oral lesion. AB - Histoplasmosis is a fungal disease resulting from inhalation of airborne spores of the organism Histoplasma capsulatum. The disease is endemic to the Ohio and Mississippi river valleys. Oral lesions are not common, but when present, they are usually associated with the severe disseminated form of histoplasmosis. This particular case is presented as an example of chronic pulmonary histoplasmosis in which a localized gingival lesion represented the initial clinical manifestation of the disease. Diagnosis was based on a positive biopsy and the results of chest radiographic examination. If, as in this case, serologic, hematologic, and physical examination results are negative, the biopsy of suspicious lesions is of paramount importance to the clinical differential diagnosis. PMID- 2911448 TI - Respiratory epithelium in an apical periodontal cyst of the mandible. AB - A cyst attached to the apex of a mandibular canine was partly lined with respiratory epithelium. This is an interesting observation for two reasons: (1) The few well-documented instances of this type of epithelium in apical periodontal cysts have been in the maxilla, where a plausible source for the respiratory epithelium for most of them was a breach in the floor of the maxillary sinus. (2) The mandibular location of the cyst reported here indicates that the respiratory epithelium within it was derived through proliferation and metaplasia of the rests of Malassez. PMID- 2911449 TI - Oral epithelial dysplasia in vitamin B12 deficiency. AB - Widespread soreness and focal ulceration of the oral mucosa developed in a woman with vitamin B12 deficiency shortly after hydroxocobalamin therapy had commenced. An oral mucosal biopsy showed disordered epithelial maturation with marked cytologic atypia. However, during the next month of treatment, the patient's oral mucosa became clinically and histologically normal. Pathologists should be aware that vitamin B12 deficiency may be associated with epithelial changes similar to those associated with premalignancy. PMID- 2911450 TI - Management of endodontic pain with nonsteroidal anti-inflammatory agents: a double-blind, placebo-controlled study. AB - The ability of two nonsteroidal anti-inflammatory agents--piroxicam and diclofenac--to control endodontic pain was compared with that of a placebo control in a double-blind study of 267 patients requiring endodontic therapy. Endodontic treatment was carried out over three visits with an interval of 5 to 7 days between each two consecutive visits. All patients were clearly instructed to take the medication only if they experienced pain, between the visits or postoperatively, for 3 consecutive days. The patients subjectively rated their pain on a scale of 1 to 4 as none, mild, moderate, or severe. The ratings were done preoperatively and at 2, 4 and 8 hours after the initial dose of medication was taken, as well as on the second and third days. Statistical analysis of the data revealed that both piroxicam and diclofenac significantly reduced the mean pain score at the end of all observations and were significantly superior to the placebo until the end of the study. More than 90% of the patients treated with piroxicam and more than 80% of the patients treated with diclofenac showed complete relief of pain. Overall, piroxicam was clearly more effective than diclofenac or the placebo. It provided more consistent relief of pain, beginning 2 hours after the initial dose, and it continued to do so at every interval thereafter. Diclofenac required longer time to reach maximum effectiveness. Piroxicam's superiority was greater at the first and second days after the initial dose of medication was taken. With respect to side effects, piroxicam was better tolerated by the patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2911451 TI - [Simultaneous occurrence of palmar and plantar fibromatosis]. PMID- 2911452 TI - [Hyponatremia caused by water intoxication induced by diuretics]. PMID- 2911454 TI - Wondering where the real power is? Look in the mirror. PMID- 2911453 TI - AARP voices concerns over RCT proposal. PMID- 2911455 TI - Nursing's presence and potential in alternative delivery systems. PMID- 2911456 TI - [Endoscopy or trial treatment of patients with dyspepsia?]. AB - The predictive value of dyspeptic symptoms is low. Upper GI endoscopy is the diagnostic gold standard, giving optimal basis for adequate drug treatment and may have a positive influence on the prognosis of non ulcer dyspepsia. Accordingly, endoscopy tends to be recommended at an early stage of chronic dyspepsia. Age above 40 years, pains relieved by food or antacids, night pains, smoking and male sex enhances the probability of an organic disease and thus the need for endoscopy. Trial treatment is recommended if the waiting period for endoscopy exceeds two weeks. Patients previously endoscoped may often be treated in accordance with earlier diagnosis and drug experience when relapsing. Drug choice when there is no firm diagnosis, should be determined by the symptom pattern. Two weeks of treatment failure necessitates endoscopy. Individual trial packages containing both the active drug and placebo could improve decision making in clinical practice. PMID- 2911457 TI - [Altitude sickness]. AB - The interest in mountain tracking and climbing has increased and there is a need for knowledge of altitude-related diseases. About one million non-acclimatized individuals annually frequent areas around 2,000 to 3,000 m above sea level and incur unpleasant symptoms in the form of acute altitude sickness or potentially fatal conditions such as pulmonary and/or cerebral oedema. Headache is the most prominent sign of acute altitude sickness but fainting fits, loss of appetite, hesitant gait, euphoria, or confusion also occur. Dyspnoea, cyanosis at rest, and a dry cough are signs of pulmonary oedema. Cerebral oedema may be feared when inexperienced climbers are afflicted by severe headaches, vomiting, and hesitant gait. Coma ensues relatively soon. Treatment consisting in descent to lower altitude, administration of oxygen, and possible medicinal therapy is effective if immediately introduced. PMID- 2911458 TI - [Irregularity of the work load and long on-duty periods are the worst problems in the working environment for physicians in the Scandinavian countries]. PMID- 2911459 TI - About the residents' working conditions in the USA. PMID- 2911460 TI - [Endocytosis, intracellular transport and sorting of proteins]. AB - A complicated interaction between outgoing and incoming protein transport occurs in eucaryotic cells. The incoming protein transport commences when protein molecules (ligands) cleave to specific glycoprotein- or glycolipid-receptors on the cell surfaces for endocytosis thereby. This can proceed in two types of membrane vesicle. Endocytosed ligands and receptors are transported from the surface of the cell to its endosomal system where a dissociation of the ligand from its receptor and sorting with regard to its next destination may occur. There are a good many possibilities of intracellular transport, depending on which ligand/receptor complex is at issue. Thus ligands and receptors can be transported back to the cell surface (recycling), across e.g. a polarized epithelial cell (transcytosis) to the lysosomes, and to the cell's Golgi apparatus. Apart from a large number of physiological ligands, viruses and diverse bacterial and plant toxins are also endocytosed. This allows scope for a therapeutic use of endocytosis. PMID- 2911461 TI - Nucleotide sequence of both reciprocal translocation junction regions in a patient with Ph positive acute lymphoblastic leukaemia, with a breakpoint within the first intron of the BCR gene. AB - Breakpoints on chromosome 22 in the translocation t(9;22) found in Philadelphia positive acute lymphoblastic leukaemia patients fall within two categories. In the first the breakpoint is localized within the breakpoint cluster region of the BCR gene, analogous to the chromosome 22 breakpoint in chronic myeloid leukaemia. The second category has a breakpoint 5' of this area, but still within the BCR gene. We have previously shown that these breakpoints occur within the first intron of the BCR gene and cloned the 9q+ junction from such a patient. We have now determined the sequences around the breakpoints on both translocation partners from this patient as well as the germline regions. The chromosome 9 ABL sequence around the breakpoint shows homology to the consensus Alu sequence whereas the chromosome 22 BCR sequence does not. At the junction there is a 6 bp duplication of the chromosome 22 sequence which is present both in the 9q+ and in the 22q- translocation products. Possible mechanisms for the generation of the translocation are discussed. PMID- 2911462 TI - Isolation of the Xenopus homolog of int-1/wingless and expression during neurula stages of early development. AB - We have isolated the Xenopus homolog (Xint-1) of the mouse protooncogene int-1 from a neurula stage 17 cDNA library. The deduced protein sequence of Xint-1 includes 371 amino acids. The Xint-1 protein is more similar to the mammalian int 1 product (69%), than to the Drosophila counterpart of int-1, wingless (50%). Xint-1 shares several characteristics of secreted proteins with the other int-1 homologs: it has a hydrophobic leader, multiple conserved potential N-linked glycosylation sites and is rich in cysteine residues. All 23 cysteines are conserved in the three proteins. Xint-1 is transiently expressed during the neurula stages of early Xenopus development. PMID- 2911463 TI - Different liver nuclear proteins binds to similar DNA sequences in the 5' flanking regions of three hepatic genes. AB - The proximal promoter region of the human transferrin gene contains an hepatocyte specific cis-element (PRI, nucleotides -76 to -51) whose DNA sequence is homologous to a sequence (nucleotides -89 to -68) present in the transcriptionally essential 5' region of the human antithrombin III gene and to another hepatocyte-specific sequence (A domain) of the human alpha 1-antitrypsin gene promoter. The results reported here lead to the conclusion that the liver trans-acting factor Tf-LF1, binding to the transferrin PRI cis-element interacts with the homologous antithrombin III region, but is different from the transcription factor LF-A1 interacting with the A domain of the alpha 1 antitrypsin promoter. The distal region DRI (nucleotides -480 to -454) of the human transferrin gene promoter presents in its core the same 10 nucleotide-long sequence as the PRI cis-element. We have previously shown that the liver protein Tf-LF2, binding to the DRI element is different from the Tf-LF1 trans-acting factor. In this paper we also show that Tf-LF2 is different from the transcription factor LF-A1 interacting with the alpha 1-antitrypsin promoter. The results allow us to conclude that at least three distinct liver nuclear proteins bind to different subsets of 5' DNA regions containing similar sequences. These sequences are present in genes expressed essentially in liver. PMID- 2911464 TI - Mouse thymidine kinase: the promoter sequence and the gene and pseudogene structures in normal cells and in thymidine kinase deficient mutants. AB - The mouse genome carries one gene and two pseudogenes for cytoplasmic thymidine kinase. The overall structure of these genes was determined with the help of cosmids and lambda phage clones and the upstream sequence containing the promoter was determined. The data allow an allocation of bands seen in the complex patterns of genomic Southern blots obtained from the DNA of wild type cells and of thymidine kinase deficient mutants to the gene as well as to the two pseudogenes. The much used LTK cell line was found to lack the entire gene but to retain the pseudogenes. Two other TK cell lines had DNA patterns indistinguishable from the wild type. Whereas the LTK line did not produce any TKmRNA, the two other mutants had normal amounts of TKmRNA but no cytoplasmic TK activity. PMID- 2911465 TI - Inhibition of human immunodeficiency virus (HIV-1) replication by synthetic oligo RNA derivatives. AB - Several synthetic 2'-O-methyl-RNA oligomers and their derivatives have been evaluated for inhibitory effect against HIV-induced cytopathic effect and expression of the virus specific antigen in cultured MT-4 cells. In this study, oligo(2'-O-methyl)ribonucleoside phosphorothioates showed a potent inhibitory activity with size dependency (25-mer showed it at 1 microM), but by contrast both 2'-O-methylribo- and deoxy-oligomers with normal phosphate linkages failed to inhibit. However, it should be noted that the patched oligo(2'-O methyl)ribonucleotide (20-mer), in which five linkages at 5'- and three linkages at 3'-ends of normal phosphates were replaced with thiophosphates, has recovered the substantial inhibitory effect. These results show that the size of oligomer and phosphorothioate linkages, probably resistant to exolytic nucleases, are essential for exhibiting antiviral activity. PMID- 2911466 TI - 5' flanking and first intron sequences of the human beta-actin gene required for efficient promoter activity. AB - We have identified a CCAAT box element that is required for the efficient transcription of the human beta-actin gene. Both in vivo transient transfection assays in cultured HeLa cells and in vitro run-off transcription assays in HeLa whole cell extracts demonstrated the requirement of this element for efficient promoter activity. A gel mobility shift assay revealed a Hela nuclear factor that specifically interacted with the beta-actin CCAAT element in vitro; mutation of the first three base pairs of the CCAAT pentanucleotide abolished binding of this factor. Competition gel shift experiments revealed that three sequence elements located within the beta-actin promoter, each containing a CC(A/T)6GG motif similar to that contained within the c-fos serum response element, were able to bind a different nuclear factor, serum response factor (SRF). One of these CC(A/T)6GG motifs is contained within a first intron fragment that enhanced transcription from a heterologous promoter in vivo. PMID- 2911468 TI - Psoralen covalently linked to oligodeoxyribonucleotides: synthesis, sequence specific recognition of DNA and photo-cross-linking to pyrimidine residues of DNA. AB - The psoralen derivative 4,5',8-trimethylpsoralen was covalently linked to the 5' terminus of an 18mer oligodeoxyribonucleotide in the course of solid phase synthesis using phosphoroamidite chemistry. The derivative was introduced as a phosphitylation compound in the last cycle of the oligomer synthesis. The reagent was prepared by 4'-chloromethylation of 4,5',8-trimethylpsoralen, introduction of a linker by ethanediol and phosphitylation with chloro-[(beta-cyanoethoxy)-N,N diisopropylamino]-phosphine. After oxydation and deprotection the 5'-psoralen modified oligodeoxyribonucleotide was characterised by HPLC. Hybridisation of the psoralen-modified oligomer to a complementary single stranded 21mer followed by irradiation at 350 nm revealed a photo-cross-linked double-stranded DNA fragment analysed on denaturing polyacrylamide gels. The cross-link could be reversed upon irradiation at 254nm. PMID- 2911467 TI - A 12 megabase restriction map at the cystic fibrosis locus. AB - We have constructed a physical map of the chromosomal region containing the cystic fibrosis locus using seven DNA markers and pulsed-field gel electrophoresis methods. The map includes cleavage sites for 8 rare-cutting restriction enzymes and spans over 12 megabases (Mb) of DNA, with one unlinked probe covering an additional 5 Mb. To our knowledge, this is the largest segment of human DNA which has been restriction-mapped to date. We can identify thirteen putative HTF islands spaced at intervals of 0.3-3.2 Mb. The region between loci D7S8 and MET, where the CF gene lies, includes 1.4-1.9 Mb of DNA. PMID- 2911469 TI - Two tissue-specific factors bind the erythroid promoter of the human porphobilinogen deaminase gene. AB - We have studied the erythroid-specific promoter of the human gene coding for Porphobilinogen Deaminase (PBGD) by DNaseI footprinting, gel retardation and methylation interference assays. We show that this promoter, which is inducible during MEL cell differentiation, contains three binding sites for the erythroid specific factor NF-E1 and one site for a second erythroid-specific factor, which we name NF-E2. NF-E1 is a factor that also binds the promoter and the enhancer (present in the 3' flanking region) of the human beta-globin gene. NF-E2 has not yet been described and although it binds to a sequence containing the Ap1 consensus, it appears to be different from Ap1. PMID- 2911470 TI - A test of 'polymerase handover' as a mechanism for stimulating initiation by RNA polymerase I. AB - On the tandemly linked ribosomal genes of Xenopus laevis, the RNA polymerase transcribes past the 3' end of the 40S coding region and terminates at T3 just upstream of the gene promoter. The close proximity of T3 to the gene promoter, and the functional interdependence of these two elements, has led to the suggestion that polymerase terminating at T3 might be passed directly to the gene promoter. Such a mechanism might be necessary to maintain the characteristic high rate of transcription initiation seen on the ribosomal genes. We have performed a direct test of this model by introducing chain-terminating psoralen adducts into a circular plasmid containing a single gene promoter with its attendant T3 region upstream. We find that the psoralen adducts can completely prevent polymerase from traveling around the template circle (and thus prevent polymerase from approaching the promoter from upstream) without affecting the rate of transcription initiation at the gene promoter. This result suggests that recycling of polymerase from T3 to the promoter is not a significant mechanism in maintaining high initiation rates. PMID- 2911471 TI - Solvent interactions stabilising nucleic acid conformers. AB - The transition of oligonucleotides from the B to the A conformation has been studied by the use of simple geometric calculations aimed at finding possible hydration sites which could stabilize these conformations. The method involves the classification of equally spaced grid points, surrounding the oligonucleotide, into groups depending on whether a water molecule, so placed, could form single, multiple or nil contacts to polar oligonucleotide atoms. The occurrence of the multiple, and therefore bridging, sites is more extensive for the 'A' than the 'B' conformation. Thus, more general evidence is presented in support of the economy of hydration hypothesis in which phosphate groups, in the low humidity 'A' form, have been seen to be bridged by single water molecules. Similar calculations for the 'Z' DNA conformation show a different preference for multiple bridging sites. PMID- 2911473 TI - Cloning and nucleotide sequence of an ovine prolactin cDNA. PMID- 2911472 TI - An extremely polymorphic locus on the short arm of the human X chromosome with homology to the long arm of the Y chromosome. AB - A genomic DNA clone named CRI-S232 reveals an array of highly polymorphic restriction fragments on the X chromosome as well as a set of non-polymorphic fragments on the Y chromosome. Every individual has multiple bands, highly variable in length, in every restriction enzyme digest tested. One set of bands is found in all males, and co-segregates with the Y chromosome in families. These sequences have been regionally localized by deletion mapping to the long arm of the Y chromosome. Segregation analysis in families shows that all of the remaining fragments co-segregate as a single locus on the X chromosome, each haplotype consisting of three or more polymorphic fragments. This locus (designated DXS278) is linked to several markers on Xp, the closest being dic56 (DXS143) at a distance of 2 cM. Although it is outside the pseudoautosomal region, the S232 X chromosome locus shows linkage to pseudoautosomal markers in female meiosis. In determining the X chromosome S232 haplotypes of 138 offspring among 19 families, we observed three non-parental haplotypes. Two were recombinant haplotypes, consistent with a cross-over among the S232-hybridizing fragments in maternal meiosis. The third was a mutant haplotype arising on a paternal X chromosome. The locus identified by CRI-S232 may therefore be a recombination and mutation hotspot. PMID- 2911474 TI - The nucleotide sequence of cDNA for a Drosophila ribosomal protein with homology to rat ribosomal protein S26. PMID- 2911475 TI - The complete cDNA sequence of mouse elongation factor 1 alpha (EF 1 alpha) mRNA. PMID- 2911476 TI - Nucleotide sequence of 5S ribosomal RNAs of 'Amphibacillus xylanus' and Clostridium carnis. PMID- 2911477 TI - Novel cDNA sequence possibly generated by alternative splicing of a mouse glucocorticoid receptor gene transcript from Shionogi carcinoma 115. PMID- 2911478 TI - Nucleotide sequence of a gene cloned from Bacillus thuringiensis subspecies entomocidus coding for an insecticidal protein toxic for Bombyx mori. PMID- 2911479 TI - Sequence criteria for Z-DNA formation: studies on poly d(ACGT). PMID- 2911480 TI - An efficient procedure for the isolation of recombinant baculovirus. PMID- 2911481 TI - A rapid procedure for colony screening using nylon filters. PMID- 2911482 TI - A simple method for direct cloning and sequencing cDNA by the use of a single specific oligonucleotide and oligo(dT) in a polymerase chain reaction (PCR). PMID- 2911483 TI - Nucleotide sequence of a uniquely expressed human T cell receptor beta chain variable region gene (V beta) in Sjogren's syndrome. PMID- 2911484 TI - c2X75, a derivative of the cosmid vector c2XB. PMID- 2911485 TI - The nucleotide sequence of 5.8S rRNA from the moss Mnium rugicum Laur. PMID- 2911486 TI - Protein sequence homology between plant 4-coumarate:CoA ligase and firefly luciferase. PMID- 2911487 TI - Nucleotide sequence of a pseudogene for rat ornithine decarboxylase. PMID- 2911488 TI - Refined crystal structure of an octanucleotide duplex with I.T. mismatched base pairs. AB - The structure of the synthetic deoxyoctamer d(GGIGCTCC) has been determined by single crystal X-ray diffraction techniques to a resolution of 1.7A. The sequence crystallises in space group P6(1), with unit cell dimensions a = b = 45.07, c = 45.49A. The refinement converged with a crystallographic residual R = 0.14 and the location of 81 solvent molecules. The octamer forms an A-DNA duplex with 6 Watson-Crick (G.C) base pairs and 2 inosine-thymine (I.T) pairs. Refinement of the structure shows it to be essentially isomorphous with that reported for d(GGGGCTCC) with the mispairs adopting a "wobble" conformation. Conformational parameters and base stacking interactions are compared to those for the native duplex d(GGGGCCCC) and other similar sequences. A rationale for the apparent increased crystal packing efficiency and lattice stability of the I.T octamer is given. PMID- 2911490 TI - Upstairs, downstairs. PMID- 2911489 TI - GATAAG; a cis-control region binding an erythroid-specific nuclear factor with a role in globin and non-globin gene expression. AB - An erythroid-specific nuclear protein factor binds to a sequence motif (GATAAG) which is present in the promoter region of the mouse alpha and beta major globin genes, and in the erythroid-specific promoter of the human porphobilinogen deaminase (PBG-D) gene. The protein activity is conserved across species, being found in mouse erythroleukaemia (MEL) cells, chicken erythrocytes, the human erythroid K562 and KMOE cell lines, but not in a variety of non-erythroid mouse tissues or in HeLa cells. Functional analysis of this element in the alpha globin gene promoter by stable transfection experiments show that the GATAAG motif resides in a 68 bp sequence which has a stimulatory effect on transcription in mouse erythroleukaemia but not fibroblast cells. The GATAAG motif is conserved in the promoters and 3' enhancers of a variety of globin and non-globin genes implying that it is a cis-element involved in the tissue-specific up-regulation of several genes that are co-expressed during erythroid cell differentiation. PMID- 2911491 TI - Updating nursing's image. PMID- 2911492 TI - Nursing's image on the university campus. AB - Our study found that the faculty sampled held a different and more positive view of nursing than the one presented by the media. Nurses were perceived as educated, autonomous and compassionate individuals whose role is vital in health care. These findings might be explained by the high degree of personal contact that the sample had with nurses. It is possible that personal contact with nurses may mediate against the negative media image of nursing. As one respondent wrote, "Nursing care after recent surgery certainly erased all stereotyped notions...." The implications are tremendous for the role of the nurse in every encounter with the public. Nursing's energies might be best directed toward promoting nursing, not as it is portrayed in the media world of make-believe, but as it is lived by real nurses and their clients. Nurses must convey an image of caring, competent professionals who are capable of addressing society's health care needs. In the words of another respondent, "Unfortunately, the American public does not know the reality of professional nursing and the nurses have been treated unfairly, far from what they deserve.... I hope the American public will look on nursing as one of the most respectable professions and give the nurses credit for their efforts, devotion, and knowledge...." PMID- 2911493 TI - What high school texts say about nursing. PMID- 2911494 TI - Work behaviors of nursing faculty. PMID- 2911495 TI - Surviving nursing's enrollment slump. PMID- 2911496 TI - Relocating faculty to an outreach site. AB - Although relocation and added job responsibilities necessitate a tremendous adjustment, the ensuing career opportunities can be personally challenging and invigorating. Pioneering an outreach effort adds a stimulating dimension to teaching. The increase in responsibility brings with it an increase in accountability. The result is an autonomy rarely found in the academic realm. PMID- 2911497 TI - Whistle-blowing by nurses: a matter of ethics. PMID- 2911498 TI - Infant mortality and public health nursing: a history of accomplishments, a future of challenges. PMID- 2911500 TI - Rationing health care violates our ethical code. PMID- 2911499 TI - Educational level and job performance. PMID- 2911501 TI - Student attitudes toward treating AIDS patients. PMID- 2911502 TI - Are you a doctor or a nurse? PMID- 2911503 TI - "Must" reading. PMID- 2911504 TI - ANA and collective bargaining. PMID- 2911505 TI - Nursing: a job or a commitment? PMID- 2911506 TI - Stress process among mothers of infants: preliminary model testing. AB - Maternal employment, cesarean birth, and infant difficultness were used to test the mediating effect of perceived stress and the stress-buffering role of health practices on maternal identity. One hundred seventy-three mothers returned a parenting survey that focused on: stressors, perceived stress, health practices, maternal identity, and a demographic profile. Work status and infant difficultness were related to perceived stress. Neither had direct effects on maternal identity, but were related to it through the mediating effects of perceived stress. While health practices did not show buffering effects between stressors and perceived stress, these did contribute additively to the prediction of stress perception. Also, health practices contributed additively to the prediction of identity. Notable among the health practices predicting identity were self-actualizing expression, nutrition, interpersonal support, and stress management. These findings support a stress process model of parenting in which: (a) effects of stressors on maternal identity are mediated by perception of stress, and (b) health practices contribute positively and directly to maternal identity. PMID- 2911507 TI - A test of two explanatory models of women's responses to battering. AB - Two theoretical models, grief and learned helplessness, were compared for relative explanatory applicability for responses of women to battering. Ninety seven battered women were compared with 96 nonbattered women who were also having serious problems in an intimate relationship with a man. The two groups were similar on the majority of model variables, including self-esteem (TSCS), self care agency (DSCAI), self-blame, depression (BDI), and control in the relationship. Both groups scored significantly below normative groups in self esteem. The battered women had more frequent and severe physical symptoms of stress and grief and had thought of or tried more solutions to the relationship problems. Both models had significant explanatory power, especially for battered women, and were equally applicable for formulating theory and nursing care interventions. PMID- 2911508 TI - A meterstone. PMID- 2911509 TI - Appraisals of bereavement, coping, resources, and psychosocial health dysfunction in widows and widowers. AB - The purpose of the study was to test a model, based on Lazarus and Folkman's (1984) stress-coping framework, on widowed persons' psychosocial health dysfunction after conjugal bereavement. Older widows (n = 100) and widowers (n = 59) were identified through church burial records and interviewed using the Ways of Coping Checklist, Sickness Impact Profile, and questionnaires to assess appraisal of bereavement and resources. Path analysis indicated that lower threat appraisal, more problem-focused and less emotion-focused coping, greater resource strength, and younger age had direct effects on reducing psychosocial health dysfunction, explaining 30% of the variance. Higher threat appraisal influenced the use of more problem- and emotion-focused coping strategies. Greater resource strength directly influenced lower threat appraisal. Sex and type of death affected psychosocial health dysfunction through their effect on resource strength. PMID- 2911510 TI - Perceived and received support: effects on health behavior during pregnancy. AB - The effects of several measures of social support on three health behavior practices during pregnancy--abstinence from alcohol, cigarettes, and caffeine- were explored. Both specificity of support and the distinction between perceived and received support were examined. The sample consisted of 529 pregnant women who completed written questionnaires and telephone interviews. Analyses showed that specific perceived and received support were significant and largely independent predictors of all three behaviors. General social support, however, was not a significant predictor of any of the behaviors. Although others have found perceived support rather than received support to be the critical component of social support in its stress-buffering effects on health, this study offers evidence that received support is also important for facilitating positive health behaviors. PMID- 2911511 TI - An evaluation of two indirect methods of blood pressure measurement in ill patients. AB - Direct (intraarterial) and two indirect (using a mercury sphygmomanometer [MS] and an automatic [auscultatory] device) methods of blood pressure measurement were compared in intensive care patients (N = 32). One trained observer blind to both automatic and direct measurements obtained all indirect MS measurements. All direct and indirect measurements were made on the same arm. Direct measurements were obtained from 10-second strip chart recordings. In normotensive patients both indirect measurements of systolic blood pressure (SBP) underestimated the direct SBP; however, only the SBP value obtained with the automatic device (106 mm Hg) was significantly different, p less than .05, from the direct SBP value (120 mm Hg). No significant difference was noted between methods in measurement of normotensive diastolic blood pressure. In hypertensive patients direct SBP was significantly greater, p less than .05, from both values obtained by indirect measurement. In patients without hypotension the automatic device may be substituted for the MS and direct blood pressure methods. The automatic device may offer the advantage of decreasing observer bias and variability in blood pressure measurement. PMID- 2911512 TI - Interactional styles of nurse practitioners and physicians regarding patient decision making. AB - The purpose of this study was to describe interactional styles used by nurse practitioners and physicians in their attempts to influence patients' decision making. The ethical concepts of paternalism, maternalism, and shared decision making (operationalized as command, consequence, and concordance, respectively) formed the conceptual framework for the analysis of the interactions. Videotaped interactions of 85 physicians and 42 nurse practitioners in either joint or solo practice were analyzed. Tests of a priori hypotheses using hierarchical log linear modeling yielded the following significant results: Males and physicians in solo practice used more command statements and fewer consequence statements than females and nurse practitioners in solo practice, who used fewer command statements and more consequence statements. All groups used more command/consequence statements than concordance statements. PMID- 2911514 TI - Re: 'Perceived self-care agency: a LISREL Factor Analysis of Bickel and Hanson's Questionnaire'. PMID- 2911515 TI - The potential uses of pilot work. PMID- 2911513 TI - Examination of a survey methodology: Dillman's Total Design Method. PMID- 2911516 TI - Management of doxorubicin extravasation. PMID- 2911517 TI - Cancer rehabilitation. Facilitating early rehabilitation in limb-salvage patients. PMID- 2911518 TI - Sexual rehabilitation of the amputee. PMID- 2911519 TI - Discussing sexuality. PMID- 2911520 TI - Setting goals in rehabilitation. PMID- 2911521 TI - Use of the wheelchair in encouraging mobility. PMID- 2911522 TI - Lactation following breast irradiation. PMID- 2911523 TI - An understudied population: the homeless. PMID- 2911524 TI - Nutrition and cancer: educating the public through a health fair. AB - Minnesota has a high incidence of dietary-associated cancer, including colorectal, breast, and prostate. To increase public awareness of cancer risks and health benefits of dietary behaviors, the Metro Minnesota Chapter of the Oncology Nursing Society (ONS) participated in a public education health fair. Supported by a Special Project Funding Grant from the ONS, 42 chapter members assisted more than 700 Metro area residents at seven locations to assess and improve their diet according to the American Cancer Society (ACS) guidelines. To evaluate the effectiveness of the project, a postcard survey was sent to 200 (29%) names randomly drawn from raffle entries. Seventy-five surveys were returned (38%). Ninety-five percent found the assessment helpful in evaluating their diet, and 80% made dietary changes in the two weeks following the health fair. Results indicate that nurses should continue to educate the public about the relationship between diet and cancer. Recommendations for further consideration include assessment of long-term effects of the health fair education format and provision of a brochure about ONS. Benefits included community education and ONS member participation in a chapter activity. PMID- 2911525 TI - Breast reconstruction using tissue expanders. AB - Breast reconstruction options are available to virtually all women undergoing mastectomy. Breast reconstruction may increase the woman's self-esteem and foster a more positive body image. Tissue expansion provides a means of developing breast symmetry with minimal surgical intervention. It can be used when the skin and soft tissue remaining after mastectomy are of good quality but inadequate quantity. The nurse's role encompasses physical and psychological support and patient education. PMID- 2911526 TI - Septic shock: special needs of patients with cancer. AB - Septic shock results in activated coagulation, cell injury, metabolic changes, and altered blood flow through the microcirculation. If left untreated, the end result is multiple organ failure and death. Patients with cancer are at increased risk of developing shock because of both host-related and treatment-related risk factors. Nursing cognizance of high-risk patients should promote close observation for signs and symptoms of early septic shock. Septic shock may be managed on the unit but signs of impending circulatory collapse and respiratory failure may warrant transferring the patient to the intensive care unit (ICU). Nursing measures include assessment, patient teaching, monitoring of all body systems, and special attention to the patient's psychosocial needs. PMID- 2911527 TI - Cancer survivors at work: job problems and illegal discrimination. AB - Approximately 25% of the five million people in the United States with a cancer history experience disparate treatment in employment solely because of their medical histories. Many employers do not realize that more than half of the people diagnosed with cancer in 1988 in the United States will overcome their illness, that cancer is not contagious, and that cancer survivors have relatively the same productivity rates as other workers. Decisions to deny employment opportunities to cancer survivors that are based on misconceptions about cancer instead of the individual's ability to perform the job may violate the survivor's legal rights. Discrimination against individuals with a history of cancer, who are qualified for jobs, violates most federal and state laws that prohibit employment discrimination based on actual or perceived disabilities. Health professionals, as well as survivors themselves, must take action on three fronts to combat cancer-based discrimination: public and professional education, individual and group advocacy, and appropriate use of legal remedies. PMID- 2911528 TI - Assessment of hope in patients with cancer: development of an instrument. AB - Hope has been identified as a vital component to individuals with cancer. This study focused on development of a reliable and valid instrument to measure hope following a stressful event as exhibited in a sample of well adults and a sample of patients with cancer. A review of the literature provided a conceptual framework for this study and the development of the Nowotny Hope Scale. Six dimensions of hope were identified and became the subscales for the instrument: confidence in the outcome, possibility of a future, relates to others, spiritual beliefs, comes from within, and active involvement. The sample consisted of 306 adults, both well and with cancer. Cronbach coefficient alpha for the scale was 0.90. Six factors were derived by principal components analysis. Study results established the instrument's initial reliability and validity. The hope scale, showing that hope is a measurable quantity, could be used in the assessment phase of the nursing process. PMID- 2911529 TI - The relationship between level of hope and level of coping response and other variables in patients with cancer. AB - This descriptive study investigated the relationship between hope using the Herth Hope Scale and coping using the Jalowiec Coping Scale in 120 adult patients undergoing chemotherapy in hospital, outpatient, and home settings. Also analyzed were length of time since diagnosis, family and job responsibilities, and religious convictions in relation to the level of hope and coping. The study found a significant relationship (p less than 0.05) between level of hope and level of coping among subjects in all three settings. In addition, strength of religious convictions and performance of family role responsibilities were significantly related to the variables of hope and coping regardless of setting. Length of time since diagnosis and performance of job role responsibilities were not significantly related to either the levels of hope or coping. PMID- 2911530 TI - Nurses' perspectives on the meaning of hope in patients with cancer: a qualitative study. AB - This study focused on developing an understanding of the meaning of hope for patients with cancer by eliciting vivid descriptions of hopeful cancer patients from clinical nurse specialists. The qualitative methodology for this study was based on one form of grounded theory. An inductive approach was applied to the development of generalized knowledge about the concept of hope. A conceptual model of hope was derived from critical attributes of hope identified within descriptions of hopeful cancer patients. Six oncology clinical nurse specialists were interviewed about their clinical experience with patients with cancer who were hopeful. Interviews were documented through process recordings. Attributes of hope were isolated and coalesced into six subthemes: goal setting, positive personal attributes, future redefinition, meaning in life, peace, and energy. Thematic analysis was used to develop a conceptual model of hope. Energy emerged as a strand running through each of the six subthemes and served as a focal point in the description and model of hope. Each of the subthemes described a component of the process whereby energy was exchanged, transformed, or moved, resulting in the preservation or loss of hope. This study generates a new way of viewing the patient with cancer and suggests several approaches for fostering hope. PMID- 2911531 TI - Why hope now? PMID- 2911532 TI - Ergotism masquerading as arteritis. PMID- 2911533 TI - Extreme pyrexia during bretylium administration. AB - Body temperatures exceeding 41.1 degrees C (106 degrees F) occur with relatively few conditions. In the unusual case reported here, the patient's temperature reached 42.3 degrees C (108.2 degrees F) during intravenous administration of bretylium for refractory ventricular fibrillation. The temperature started to drop as soon as the infusion was stopped and was close to normal within four hours. This appears to be the first report of extreme pyrexia resulting from use of this agent. PMID- 2911534 TI - Delirium in the elderly. A commonly misunderstood disorder. PMID- 2911535 TI - Health hazards of working with ceramics. Recommendations for reducing risks. AB - Ceramics artists are at risk for pulmonary disease, heavy metal poisoning, and other toxic reactions caused by exposure to clays, glazes, and kiln emissions. Stringent personal hygiene, awareness of hazardous materials, and appropriate safety measures may reduce the health risks of repeated exposures. PMID- 2911536 TI - Paraneoplastic syndromes. How to recognize the remote neurologic effects of cancer. AB - Neurologic paraneoplastic syndromes occur in patients with all forms of malignancy. Their effects on the central and peripheral nervous systems are devastating. A neurologic abnormality may be the first manifestation of malignancy or can occur late in the course of the disease. Early recognition can lead to effective treatment of a paraneoplastic syndrome and a potential cure of the underlying cancer. PMID- 2911537 TI - Fine-needle aspiration biopsy. Diagnosis of cancerous masses in the office. AB - Fine-needle aspiration biopsy is a rapid, inexpensive, atraumatic, and accurate way of diagnosing many cancers. It can be applied to any palpable mass. Deep lesions can also be sampled if visualization is guided by computed tomography, ultrasound, or fluoroscopy. Proper technique is essential in obtaining biopsy material, and interpretation of the smear requires special training. Patients accept the procedure, and even a repetition of it if necessary, very well. PMID- 2911538 TI - Major burns. What to do at the scene and en route to the hospital. AB - Patients with major burns should be transported by whatever conveyance seems appropriate to a facility capable of caring for such injuries. At the scene of the accident and en route to the hospital, adherence to standard principles of trauma care allows optimal resuscitation. Once rescuers have assessed the depth and extent of burns and conferred with hospital personnel, they need to do relatively little in the way of initial wound treatment except to prevent further injury and decrease pain. Careful, concise documentation is necessary to assure a continuum of good patient care. PMID- 2911539 TI - Hospital care of major burns. AB - The burn patient initially requires many of the same measures as any other trauma patient. Both depth and surface extent of the burn injury should be evaluated. Evaluation for smoke inhalation is important, since this is prevalent and life threatening among burn victims. A treatment plan begins with a realistic appraisal of the probability of survival. Once goals of management have been established, treatment is aimed at both physiologic and aesthetic rehabilitation. PMID- 2911540 TI - Treating minor burns. Ice, grease, or what? AB - Minor burns are common but require early and appropriate care to avoid infection and scarring. Damage can be arrested by immersing the burn in cold water as soon as possible. The goals of care are then to remove dead tissue and protect viable tissue during healing. Very superficial burns require only application of an emollient to limit inflammation and pain and prevent desiccation. Partial thickness burns that are clean and superficial may benefit from use of a biosynthetic bilaminar membrane dressing, which forms a skin substitute while protecting the wound. A patient with an infected wound or one on a primary area (hands, feet, face, or perineum) may have to be hospitalized to ensure proper care. PMID- 2911541 TI - Exercise during pregnancy. Guidelines and controversies. PMID- 2911543 TI - School phobia. Sometimes a child or teenager has a good reason. AB - School phobia is a syndrome of childhood characterized by marked anxiety about attending school or by absence from school. In most cases, the underlying cause is separation anxiety. Somatic complaints may accompany the refusal to attend school. The physician should first help parents to return the child to school as soon as possible and then try to determine and alleviate the cause of the phobia. The prognosis is relatively good in preadolescent children and relatively poor in older children. PMID- 2911542 TI - Antidepressants and the cardiac patient. Selecting an appropriate medication. PMID- 2911544 TI - Testing for human immunodeficiency virus. What to do if the result is positive. PMID- 2911545 TI - Joint pain. It isn't always arthritis. AB - When a history of trauma or overuse is absent in a patient presenting with pain and stiffness in a joint, bursitis and tendinitis should be considered, especially if the patient is elderly. Appropriate questioning can narrow the differential diagnosis, and physical examination confirms the impression gathered by history taking. Treatment may include one or more injections of a local anesthetic (with or without a long-acting corticosteroid), use of an oral corticosteroid or nonsteroidal antiinflammatory agent, and in some cases, surgery. PMID- 2911546 TI - Diabetic foot ulcers. What can be done to prevent and control them. PMID- 2911547 TI - Laboratory tests in the elderly. What is abnormal? AB - Comparison of studies on the elderly is difficult. This study is one of the largest done on healthy, ambulatory persons aged 65 and up. Findings indicate that most laboratory values in elderly persons fall in the normal range. A significantly abnormal test result should raise the suspicion of underlying disease. A small percentage of patients show an abnormality on specific tests (ie, for glucose, calcium, serum lipids). Changes in a few test values are to be expected with aging: These include an increase in alkaline phosphatase, a decrease in serum phosphorus, a decrease in creatinine clearance without a concomitant rise in serum creatinine, and an increase in postprandial glucose level. Vitamin deficiencies and decrease in serum albumin are usually the result of chronic malnutrition rather than aging. PMID- 2911548 TI - Muscarinic poisoning from medications and mushrooms. A puzzling symptom complex. AB - A mixture of signs and symptoms can occur with muscarinic poisoning from medications or mushrooms. Manifestations may vary even among persons who ingested mushrooms grown in the same patch and gathered at the same time. Confusion can occur if mushroom poisoning is attributed to a suspected species rather than to the toxin suggested by signs and symptoms. Accurate diagnosis depends on clinical suspicion and recognition of muscarinic manifestations, notably diaphoresis, salivation, bladder cramping, diarrhea, and difficulty with visual accommodation. Muscarinic toxicity due to medications necessitates an adjustment in drug dosage. In mushroom poisoning that produces primarily muscarinic effects, atropine is the treatment of choice. PMID- 2911550 TI - Use of lozenges may cause dry mouth. PMID- 2911549 TI - Reduce stress with a leisurely lunch. PMID- 2911551 TI - Modified vs conventional circumcision. PMID- 2911552 TI - Yet another hazard of smoking. PMID- 2911553 TI - Otitis media. Update on a common, frustrating problem. AB - Otitis media is extremely common in infants and young children and has important ramifications for the children, their families, and society in general. The essential elements of management are early diagnosis, adequate therapy with appropriate antibacterial agents, and conscientious follow-up to promptly detect and treat potential and actual complications. The primary care physician who treats young children is the critical health-care provider in the diagnosis of otitis media, initial treatment, and timely referral when appropriate. PMID- 2911554 TI - Management of basal cell carcinoma. Which option is best? AB - Basal cell carcinoma, the most common type of skin cancer, can be treated successfully by a variety of methods. The most commonly employed techniques are curettage with electrodesiccation, scalpel excision, Mohs' chemosurgery, cryosurgery, and radiation therapy, all of which have advantages and disadvantages. The primary care physician needs to be aware of available forms of therapy, problems with recurrent lesions, and the importance of adequate follow up. PMID- 2911555 TI - Don't treat nurses as if they were invisible. PMID- 2911556 TI - Using the laboratory effectively without running up the bill unnecessarily. PMID- 2911557 TI - Three-dimensional structures of proteins in solution by nuclear magnetic resonance spectroscopy. AB - Nuclear magnetic resonance (NMR) spectroscopy has emerged in recent years as a powerful method for the determination of three dimensional structures of small proteins in solution. Major cornerstones towards these advances were the introduction of two dimensional NMR experiments in combination with high field superconducting magnets, as well as the development of computational procedures to convert NMR derived distances into a 3D structure. This article outlines the methodology employed and illustrates its applicability based on a variety of examples. PMID- 2911558 TI - Structural studies on the allergen Der p1 from the house dust mite Dermatophagoides pteronyssinus: similarity with cysteine proteinases. AB - A major allergen (Der p1) has been purified to homogeneity from faecal particles from the house dust mite Dermatophagoides pteronyssinus. Reversed-phase microbore HPLC was employed to fractionate and purify a number of tryptic peptides generated from approximately 20 nmol of purified Der p1. N-Terminal amino acid sequence analyses were performed on the intact polypeptide and six tryptic peptides yielding 89 unique assignments; this corresponds to 40% of the molecule. These data are compared with the cDNA-deduced amino acid sequence of the Der p1 allergen. There is extensive similarity between the N-terminal amino acid sequence of Der p1 and the cysteine proteases actinidin and papain. A low Mr protein (approximately 17,000) was resolved from S-carboxymethyl Der p1 by gel permeation chromatography. Edman degradation of the first 24 residues of this material revealed no similarity with Der p1. It is not clear whether this component is a low Mr disulfide-linked chain derived from Der p1 or represents an unidentified mite component. PMID- 2911559 TI - Creation of a nuclear magnetic resonance data repository and literature database. AB - We believe the need exists for an organized and accessible repository of protein nuclear magnetic resonance data. The structure and dynamics of hundreds of proteins are being investigated by NMR. NMR data currently are spread throughout the world and often are not published for lack of journal space. Difficulties in locating, obtaining, and correlating these data with protein structures limits their usefulness to the scientific community. In time, the data may become lost or ignored. To provide a collection point for the results of protein NMR studies and a uniform means of distributing these data, we propose that a data bank be created consisting of two databases: a comprehensive and thoroughly indexed database for the NMR literature and a data repository for the storage of extensive protein NMR data sets. Our current specifications for the types of information to be stored in the NMR databases and their organization for dissemination are defined. The design is intended to be flexible, capable of expanding to include new techniques, new forms of data, and biopolymers other than proteins. This is a proposal to the community of NMR spectroscopists. Only through the active cooperation and support of those in the field of NMR spectroscopy can the proposed data bank succeed. PMID- 2911560 TI - Protein sequence database of the protein identification resource (PIR). PMID- 2911561 TI - Structure of the human insulin receptor gene and characterization of its promoter. AB - The human insulin receptor gene, INSR, and its promoter region have been isolated and characterized. The gene spans greater than 120 kilobase pairs (kbp) and has 22 exons. All introns interrupt protein coding regions of the gene. The 11 exons encoding the alpha subunit of the receptor are dispersed over greater than 90 kbp, whereas the 11 exons encoding the beta subunit are located together in a region of approximately 30 kbp. Three transcriptional initiation sites have been identified and are located 276, 282, and 283 bp upstream of the translation initiation site. In addition, a 247-bp fragment from the promoter region possessing 62.6% of the maximal promoter activity has been identified. This promoter-active fragment lacks a TATA-like sequence but has two possible binding regions for the transcriptional factor Sp1. Comparison of the exon structure of the tyrosine kinase domain of the INSR with the corresponding regions of the human SRC, ROS, and ERBB2 (NGL) protooncogenes indicates that the exon-intron organization of this region has not been well conserved. PMID- 2911562 TI - Rate, origin, and bidirectionality of Caulobacter chromosome replication as determined by pulsed-field gel electrophoresis. AB - Cell division in Caulobacter crescentus yields progeny cells that differ with respect to cell structure and developmental program. Chromosome replication initiates in the daughter stalked cell but is repressed in the daughter swarmer cell until later in the cell cycle. To study cell-type-specific DNA initiation, chromosome replication was directly analyzed by pulsed-field gel electrophoresis. Analysis of Dra I restriction fragments of DNA taken at various times from synchronized cell cultures labeled with 2'-deoxy[3H]guanosine has allowed us to determine the origin of DNA replication, the rate and direction of fork movement, and the order of gene replication. The first labeled Dra I fragment to appear contains the site of replication initiation. Based on the correlation of the physical and genetic maps derived by Ely and Gerardot [Ely, B. & Gerardot, C. J. (1988) Gene 68, 323-333], the origin was localized to a 305-kilobase fragment containing the rrnA gene. Furthermore, the sequential replication through unmapped Dra I fragments has enabled us to localize their positions on the genome. The order of appearance of labeled restriction fragments revealed that the chromosome replicates bidirectionally at a fork movement rate of 21 kilobases per minute. PMID- 2911563 TI - RNA polymerase II is capable of pausing and prematurely terminating transcription at a precise location in vivo and in vitro. AB - By using the minute virus of mice, we have shown that in vivo and in vitro RNA polymerase II pauses or prematurely terminates transcription at a specific location 142-147 nucleotides downstream from the P4 promoter. The attenuated RNA was found and mapped in vivo in A9 cell late after infection in both the nuclear and cytoplasmic fractions, and the terminal nucleotide was shown to have a 3' OH group. The 3' end of the attenuated RNA is capable of forming a hairpin structure that is followed by a stretch of uridines. To distinguish whether the attenuated RNA is formed as a result of processing, pausing, or termination and to dissect structural elements, factors, or mechanisms that are involved in its formation, we used in vitro systems: isolated nuclei and cell-free extracts from HeLa cells. The results of the in vitro studies show that the attenuated RNA is a result of pausing or termination and not processing. Additionally, a salt-soluble factor and RNA secondary structure were implicated in the process of termination. PMID- 2911564 TI - Limit-cycle oscillations and chaos in reaction networks subject to conservation of mass. AB - A cyclic network of autocatalytic reactions involving an unbuffered cofactor and a number of components subject to conservation of mass displays a surprising richness of dynamical behaviors. Limit-cycle oscillations are possible over a wide range of parameter values. Additionally, a cascade of period-doubling bifurcations leading to chaos can coexist with a multiplicity of stable steady states. These results draw attention to the role of unbuffering as a feedback in biochemical systems. PMID- 2911565 TI - Protein secondary structure prediction with a neural network. AB - A method is presented for protein secondary structure prediction based on a neural network. A training phase was used to teach the network to recognize the relation between secondary structure and amino acid sequences on a sample set of 48 proteins of known structure. On a separate test set of 14 proteins of known structure, the method achieved a maximum overall predictive accuracy of 63% for three states: helix, sheet, and coil. A numerical measure of helix and sheet tendency for each residue was obtained from the calculations. When predictions were filtered to include only the strongest 31% of predictions, the predictive accuracy rose to 79%. PMID- 2911566 TI - Circadian regulation of bioluminescence in Gonyaulax involves translational control. AB - A 10-fold circadian variation in the amount of luciferin binding protein (LBP) in the marine dinoflagellate Gonyaulax polyedra is reported. This protein binds and stabilizes luciferin, the bioluminescence substrate. In early night phase, when bioluminescence is increasing and LBP levels are rising in the cell, pulse labeling experiments show that LBP is being rapidly synthesized in vivo. At other times, the rate of LBP synthesis is at least 50 times lower, while the rate of synthesis of most other proteins remains the same. The LBP mRNA levels, as determined by in vitro translations and by RNA (Northern) hybridizations, do not vary over the daily cycle, indicating that circadian control of bioluminescence in this species is mediated by translation. PMID- 2911567 TI - Chromatin architecture and nuclear RNA. AB - The maintenance of normal chromatin morphology requires ongoing RNA synthesis. We have examined the role of RNA in chromatin organization, using selective detergent extraction of cells, RNA synthesis inhibitors, and enzymatic digestion of nuclear RNA. Comparison of extracted and unextracted cells showed that the important features of chromatin architecture were largely unchanged by the extraction procedure. Normally, chromatin was distributed in small heterochromatic regions and dispersed euchromatic strands. Ribonucleoprotein granules were dispersed throughout the euchromatic regions. Exposure to actinomycin led to the redistribution of chromatin into large clumps, leaving large empty spaces and a dense clustering of the remaining ribonucleoprotein granules. When the nuclei of extracted cells were digested with RNase A, there was a rearrangement of chromatin similar to but more pronounced than that seen in cells exposed to actinomycin. The inhibitor 5,6-dichloro-1-beta-D ribofuranosylbenzimidizole also inhibits RNA synthesis but by a different mechanism that leaves no nascent RNA chains. The drug had little effect on chromatin after brief exposure but resembled actinomycin in its effect at longer times. We also examined the structure of the nuclear matrix to which most heteronuclear RNA remains associated. Pretreatment of cells with actinomycin or digestion of the nuclear matrix with RNase A caused the matrix fibers to collapse and aggregate. The experiments show a parallel decay of chromatin and of nuclear matrix organization with the depletion of nuclear RNA and suggest that RNA is a structural component of the nuclear matrix, which in turn may organize the higher order structure of chromatin. PMID- 2911568 TI - Macromolecular organization of human centromeric regions reveals high-frequency, polymorphic macro DNA repeats. AB - To analyze the macromolecular organization of human centromeric regions, we used alpha-satellite, or alphoid, repetitive DNA sequences specific to the centromeres of human chromosomes 6 (D6Z1), X (XC), and Y (YC-2) and the technique of pulsed field gel electrophoresis. Genomic DNA from 24 normal, unrelated individuals was digested and separated into fragments ranging from 23 kilobases (kb) to 2 megabases (Mb) in length. Digestion with 12 different restriction enzymes with 4- to 8-base-pair recognition sequences and hybridization with alphoid sequences revealed chromosome-specific hybridization patterns. Similarities in the organization of the centromeric regions of the three chromosomes included NotI, SfiI, and SalI fragments of greater than 2 Mb and Sau3A1 and Alu I fragments of less than 150 kb. Each restriction enzyme with a 6-base-pair recognition sequence (Ava II, BamHI, HindIII, Hpa I, Pst I, Sal I, Sst I, and Xba I) detected polymorphic DNA fragments of 50 kb to 2 Mb. Forty percent or more of the individuals screened revealed a unique hybridization pattern with these enzymes and at least one of the three chromosome-specific alphoid probes. Five individuals differed from one another in hybridization pattern for each of the three enzymes HindIII, HpaI, and SstI and for each of the three centromeric probes. All 24 individuals could be distinguished on the basis of unique hybridization patterns with only two enzymes and one chromosome-specific alphoid probe. Family studies showed that these polymorphisms are inherited. The high frequency of these macro restriction fragment length polymorphisms illustrates the high degree of variability of the centromeric region among normal individuals and demonstrates its usefulness for DNA fingerprinting and pericentromeric mapping by linkage analysis. PMID- 2911569 TI - Expression and replication of hepatitis B virus genome in transgenic mice. AB - We produced transgenic mice by microinjecting a partial tandem duplication of the complete hepatitis B virus (HBV) genome into fertilized eggs of C57BL/6 mice. One of eight transgenic mice was a high producer for HBV surface antigen (HBsAg) and HBV e antigen (HBeAg) in the serum. The HBV genomes were transmitted to the next generation and these F1 mice also produced HBsAg and HBeAg. mRNAs of 3.5, 2.1, and 0.8 kilobases were detected in the livers and the kidneys of these mice. In addition, a 0.8-kilobase RNA was detected in the testis. Single-stranded and partially double-stranded HBV DNAs were shown to be produced in the cytoplasm of the liver and kidneys. These HBV DNAs were associated with the core particles, indistinguishable from nucleocapsid produced in an infected human liver. Viral genome DNA was detected in the serum. These results demonstrate that the HBV genome integrated into the mouse chromosome acted as a template for viral gene expression, allowing viral replication. Thus, these transgenic mice should be useful for detailed studies of the replication and expression of HBV and for pathological studies of hepatitis, including the development of hepatocellular carcinoma. PMID- 2911571 TI - Processing at the carboxyl terminus of nascent placental alkaline phosphatase in a cell-free system: evidence for specific cleavage of a signal peptide. AB - Alkaline phosphatase is anchored to the plasma membrane by a carboxyl-terminal phosphatidylinositol glycan moiety. To investigate the biosynthesis of mature alkaline phosphatase, nascent human placental alkaline phosphatase was expressed in a cell-free system and used as substrate for in vitro processing by microsomal extracts. By monitoring the processed product with three site-directed antibodies, it was shown that microsomal extracts from CHO cells that contain other recognized processing activities also remove the carboxyl-terminal signal peptide from the preproenzyme in an apparently selective manner. This peptidase like cleavage may be brought about by the action of a specific transamidase acting on the nascent protein in the absence of an appropriate phosphatidylinositol glycan cosubstrate. PMID- 2911570 TI - Rapid typing of tandemly repeated hypervariable loci by the polymerase chain reaction: application to the apolipoprotein B 3' hypervariable region. AB - The 3' flanking region of the apolipoprotein B (apoB) gene contains a hypervariable region consisting of a variable number of tandemly repeated short A + T-rich DNA sequences (VNTRs). We present a general method that utilizes the polymerase chain reaction to rapidly and accurately type this and other VNTR loci. We use tailored oligonucleotides and thermostable Taq polymerase to amplify the targeted region. The amplification products are directly visualized after agarose gel electrophoresis. Twelve alleles were readily identified in a sample of 125 unrelated individuals. The alleles differ with respect to the length of the amplified gene region. This genetic variability is inherited in an autosomal codominant manner. DNA sequence data indicate that individual alleles differ in the number of repeat units and the sensitivity of the technique is such that alleles differing in length by only 32 base pairs are readily distinguishable. A system of nomenclature based on the number of repeat units is suggested; an allele containing 37 repeat units is designated 3' beta 37, one containing 35 units is 3' beta 35, and so on. The frequency distribution of the 12 apoB VNTR alleles is bimodal with peaks at 37 and 47 repeat units and a nadir near 43 repeat units. We estimate that the 3' apoB VNTR locus has a heterozygosity index of 0.75 and a polymorphic information content of 0.73. It is a highly informative marker for genetic linkage studies on chromosome 2 and clinical and epidemiological studies involving the apoB gene. The high sensitivity and inexpensive nature of this technique make it superior to traditional Southern blot analysis for typing the 3' apoB VNTR. The method described is also directly applicable for rapid typing of other VNTRs in the human genome. PMID- 2911572 TI - Mapping to molecular resolution in the T to H-2 region of the mouse genome with a nested set of meiotic recombinants. AB - We describe a meiotic fine-structure mapping strategy for achieving molecular access to developmental mutations in the mouse. The induction of lethal point mutations with the potent germ-line mutagen N-ethyl-N-nitrosourea has been reported. One lethal mutation of prime interest is an allele at the quaking locus on chromosome 17. To map this mutation, quaking(lethal-1), we have intercrossed hybrid mice that carry distinct alleles at many classical and DNA marker loci on proximal chromosome 17. From this cross we have obtained 337 animals recombinant in the T to H-2 region. This number of crossovers provides a mapping resolution in the size range of single mammalian genes if recombinational hot spots are absent. DNA samples obtained from these recombinant animals can be used retrospectively to map any restriction fragment length polymorphism in the region. This set of DNA samples has been used to map the molecular marker D17RP17 just distal of quaking(lethal-1). With the nested set of crossover DNA samples and appropriate cloning techniques, this tightly linked marker can be used to clone the quaking locus. PMID- 2911573 TI - Insect immunity: isolation from immune blood of the dipteran Phormia terranovae of two insect antibacterial peptides with sequence homology to rabbit lung macrophage bactericidal peptides. AB - We have isolated from the hemolymph of immunized larvae of the dipteran insect Phormia terranovae two peptides that are selectively active against Gram-positive bacteria. They are positively charged peptides of 40 residues containing three intramolecular disulfide bridges and differ from one another by only a single amino acid. These peptides are neither functionally nor structurally related to any known insect immune response peptides but show significant homology to microbicidal cationic peptides from mammalian granulocytes (defensins). We propose the name "insect defensins" for these insect antibiotic peptides. PMID- 2911574 TI - Sequence investigation of the major gastrointestinal tumor-associated antigen gene family, GA733. AB - The monoclonal antibody-defined, tumor-associated antigen GA733 was purified from the SW948 human colorectal carcinoma cell line and its partial amino acid sequence was determined. By using a synthetic oligonucleotide probe, two recombinants were isolated from a total human genomic library. We prove the existence of a family of GA733 genes. One of the genomic isolates is demonstrated to be an intronless gene, which is transcribed in pancreatic carcinoma cell lines and in placenta. The GA733 proteins were observed to contain sequences homologous to a repeat unit occurring 10 times in thyroglobulin and once in the HLA-DR associated invariant chain. A more evolutionarily distant relationship was found with the alpha chain of the interleukin 2 growth factor receptor. PMID- 2911575 TI - Protection of rhesus monkeys from fatal Lassa fever by vaccination with a recombinant vaccinia virus containing the Lassa virus glycoprotein gene. AB - Lassa fever is an acute febrile disease of West Africa, where there are as many as 300,000 infections a year and an estimated 3000 deaths. As control of the rodent host is impracticable at present, the best immediate prospect is vaccination. We tested as potential vaccines in rhesus monkeys a closely related virus, Mopeia virus (two monkeys), and a recombinant vaccinia virus containing the Lassa virus glycoprotein gene, V-LSGPC (four monkeys). Two monkeys vaccinated with the New York Board of Health strain of vaccinia virus as controls died after challenge with Lassa virus. The two monkeys vaccinated with Mopeia virus developed antibodies measurable by radioimmunoprecipitation prior to challenge, and they survived challenge by Lassa virus with minimal physical or physiologic disturbances. However, both showed a transient, low-titer Lassa viremia. Two of the four animals vaccinated with V-LSGPC had antibodies to both Lassa glycoproteins, as determined by radioimmunoprecipitation. All four animals survived a challenge of Lassa virus but experienced a transient febrile illness and moderate physiologic changes following challenge. Virus was recoverable from each of these animals, but at low titer and only during a brief period, as observed for the Mopeia-protected animals. We conclude that V-LSGPC can protect rhesus monkeys against death from Lassa fever. PMID- 2911576 TI - Cloning and expression of the gene cluster encoding key proteins involved in acetyl-CoA synthesis in Clostridium thermoaceticum: CO dehydrogenase, the corrinoid/Fe-S protein, and methyltransferase. AB - Acetogenic bacteria fix CO or CO2 by a pathway of autotrophic growth called the acetyl-CoA (or Wood) pathway. Key enzymes in the pathway are a methyltransferase, a corrinoid/Fe-S protein, a disulfide reductase, and a carbon monoxide dehydrogenase. This manuscript describes the isolation of the genes that code for the methyltransferase, the two subunits of the corrinoid/Fe-S protein, and the two subunits of carbon monoxide dehydrogenase. These five genes were found to be clustered within an approximately 10-kilobase segment on the Clostridium thermoaceticum genome. The proteins were expressed at up to 5-10% of Escherichia coli cell protein, and isopropyl beta-D-thiogalactopyranoside had no effect on the levels of expression, implying that the C. thermoaceticum inserts contained transcriptional and translational signals that were recognized by E. coli. The methyltransferase is expressed in E. coli in a fully active dimeric form with a specific activity and heat stability similar to the enzyme expressed in C. thermoaceticum. However, both the corrinoid/Fe-S protein and carbon dioxide dehydrogenase, although expressed in high amounts and with identical subunit molecular weights in E. coli, are inactive and less heat stable than are the native enzymes from C. thermoaceticum. PMID- 2911577 TI - Human anti-endoplasmic reticulum antibodies in sera of patients with halothane induced hepatitis are directed against a trifluoroacetylated carboxylesterase. AB - Previous studies have demonstrated that patients with halothane-induced hepatitis have serum antibodies that are directed against novel liver microsomal neoantigens and have suggested that these neoantigens may play an immunopathological role in development of the patients' liver damage. These investigations have further revealed that the antibodies are directed against distinct polypeptide fractions (100 kDa, 76 kDa, 59 kDa, 57 kDa, 54 kDa) that have been covalently modified by the reactive trifluoroacetyl halide metabolite of halothane. In this paper, the trifluoroacetylated (TFA) 59-kDa neoantigen (59 kDa-TFA) recognized by the patients' antibodies was isolated from liver microsomes of halothane-treated rats by chromatography on an immunoaffinity column of anti-TFA IgG. Antibodies were raised against the 59-kDa-TFA protein and were used to purify the native protein from liver microsomes of untreated rats. Based upon its apparent monomeric molecular mass, NH2-terminal amino acid sequence, catalytic activity, and other physical properties, the protein has been identified as a previously characterized microsomal carboxylesterase (EC 3.1.1.1). A similar strategy may be used to purify and characterized neoantigens associated with other drug toxicities that are believed to have an immunopathological basis. PMID- 2911578 TI - Characterization and expression of a cDNA encoding the human androgen receptor. AB - We report the isolation of a cDNA that encodes the complete human androgen receptor. The cDNA predicts a protein of 917 amino acids with a molecular weight of 98,918. Introduction of the cDNA into heterologous mammalian cells caused expression of high levels of a protein that binds dihydrotestosterone with the affinity, specificity, and sedimentation properties characteristic of the native human androgen receptor. Comparisons with the amino acid sequence of previously cloned steroid hormone receptors revealed a high degree of sequence conservation with the progesterone, glucocorticoid, and mineralocorticoid receptors in the putative hormone and DNA-binding domain regions. PMID- 2911579 TI - Marked in vivo antiretrovirus activity of 9-(2-phosphonylmethoxyethyl)adenine, a selective anti-human immunodeficiency virus agent. AB - 9-(2-Phosphonylmethoxyethyl)adenine (PMEA) is a potent and selective inhibitor of the replication of human immunodeficiency virus (HIV) in vitro in human T lymphocyte MT-4, H9, and ATH8 cells. PMEA also inhibits Moloney murine sarcoma virus (Mo-MSV)-induced transformation of murine C3H embryo fibroblasts. Moreover, PMEA causes a dose-dependent suppression of tumor formation and associated mortality in mice inoculated with Mo-MSV. At a dose of 50 or 20 mg/kg per day PMEA effected a 90-100% protection of the mice against Mo-MSV-induced tumor formation and mortality. Even with a PMEA dose as low as 1 to 5 mg/kg per day, tumor formation was significantly delayed and the survival rate was significantly enhanced. In parallel experiments, azidothymidine exhibited a comparable inhibitory effect on Mo-MSV-induced tumor formation and associated death only at a 25-fold higher dose than PMEA. Because PMEA has stronger in vivo antiretrovirus potency and selectivity than azidothymidine and various other compounds currently being subjected to clinical trials, PMEA studies should be pursued to assess the potential of this compound in the treatment of acquired immunodeficiency syndrome (AIDS) and other retrovirus infections in humans. PMID- 2911580 TI - Visual responses of neurons in somatosensory cortex of hamsters with experimentally induced retinal projections to somatosensory thalamus. AB - These experiments investigate the capacity of thalamic and cortical structures in a sensory system to process information of a modality normally associated with another system. Retinal ganglion cells in newborn Syrian hamsters were made to project permanently to the main thalamic somatosensory (ventrobasal) nucleus. When the animals were adults, single unit recordings were made in the somatosensory cortices, the principal targets of the ventrobasal nucleus. The somatosensory neurons responded to visual stimulation of distinct receptive fields, and their response properties resembled, in several characteristic features, those of normal visual cortical neurons. In the visual cortex of normal animals and the somatosensory cortex of operated animals, the same functional categories of neurons occurred in similar proportions, and the neurons' selectivity for the orientation or direction of movement of visual stimuli was comparable. These results suggest that thalamic nuclei or cortical areas at corresponding levels in the visual and somatosensory pathways perform similar transformations on their inputs. PMID- 2911581 TI - High-level erythroid expression of human alpha-globin genes in transgenic mice. AB - The human alpha 1-globin gene was fused downstream of two erythroid-specific DNase I super-hypersensitive sites that are normally located upstream of the human beta-globin locus. This construct was injected into fertilized mouse eggs, and expression was analyzed in 16-day fetal livers and brains. All 11 fetuses that contained intact copies of the transgene expressed correctly initiated human alpha-globin mRNA in the erythroid fetal liver but not in brain. Levels of expression ranged from 4% to 337% of endogenous mouse beta-globin mRNA. A human alpha-globin construct that did not contain super-hypersensitive sites was not expressed. These results demonstrate that human beta-globin locus activation sequences can stimulate high levels of human alpha-globin gene expression in erythroid tissue of transgenic mice. The results also provide a foundation for experiments designed to coexpress human alpha- and beta-globin genes in transgenic mice and suggest a feasible approach for production of a mouse model for human sickle cell disease. PMID- 2911582 TI - Sex- and hormone-dependent antigen immunoreactivity in developing rat hypothalamus. AB - Morphological sex differences in adults can result from differential gonadal steroid exposure during critical perinatal periods. This study describes the use of a monoclonal antibody we have developed to study mechanisms of sexual differentiation of brain structure and function. Used as a marker in immunocytochemistry, antibody AB-2 revealed subsets of cells, including radial glia, transiently during the perinatal period. Peak reactivity in radial glia was on embryonic day 19 in males and on postnatal day 1 in females. On postnatal day 1, AB-2 immunoreactivity in radial glia was 2-fold greater in females than in males. Greater activity was detected in males on one side of the brain than the other (2- to 4-fold, depending on the region). To test the hormone dependence of this sex difference, pregnant rats were injected with testosterone propionate to expose fetal females to androgen on embryonic day 18. This resulted in lower levels of AB-2 immunoreactivity in radial glia of the treated female offspring on postnatal day 1 relative to control females, and the pattern was bilaterally asymmetric, approaching that of males. Thus the difference between sexes in immunoreactivity with AB-2 as a marker was hormone dependent in a predictable manner. Whether this marker is revealing a sex difference in accessibility of antigen by immunocytochemistry or a sex difference in intrinsic antigen levels is not yet resolved. In either case these results support the hypothesis that certain hormone-dependent molecular events occur transiently during development. PMID- 2911583 TI - Aldosterone stimulates K secretion across mammalian colon independent of Na absorption. AB - K transport across guinea pig (Cavia porcellus) distal colon was measured in vitro using isotopically determined unidirectional fluxes. Aldosterone stimulated electrogenic Na absorption, as measured by amiloride-sensitive short-circuit current (Isc), and reduced net K absorption from +2.5 +/- 0.2 microEq/cm2 per hr to +0.8 +/- 0.3 microEq/cm2 per hr (mean +/- SEM). Amiloride addition to the mucosal solution did not enhance net K absorption, as expected if inhibiting active Na absorption would reduce active K secretion as in the distal nephron. The amiloride-insensitive Isc was -1.0 +/- 0.2 microEq/cm2 per hr (mean +/- SEM) and was inhibited by mucosal addition of Ba, a K channel blocker. Addition of bumetanide to the serosal solution also inhibited this negative Isc, and K transport returned to the control level of net absorption. Thus, the amiloride insensitive, negative Isc is consistent with active K secretion stimulated by aldosterone. This stimulation of an active K secretory pathway by aldosterone occurred without altering the active K absorption pathway that also is present. These results indicate that the aldosterone-stimulated K secretory pathway operates independently of the amiloride-sensitive Na absorption pathway, which also is stimulated by aldosterone. PMID- 2911584 TI - Structure of human neutrophil elastase in complex with a peptide chloromethyl ketone inhibitor at 1.84-A resolution. AB - Human neutrophil elastase (HNE) has been implicated as a major contributor to tissue destruction in various disease states, including emphysema. The structure of HNE, at neutral pH, in complex with methoxysuccinyl-Ala-Ala-Pro-Ala chloromethyl ketone (MSACK), has been solved and refined to an R factor of 16.4% at 1.84-A resolution. Results are consistent with the currently accepted mechanism of peptide chloromethyl ketone inhibition of serine proteases, in that MSACK cross-links the catalytic residues His-57 and Ser-195. The structure of the HNE-MSACK complex is compared with that of porcine pancreatic elastase in complex with L-647,957, a beta-lactam inhibitor of both elastases. The distribution of positively charged residues on HNE is highly asymmetric and may play a role in its specific association with the underlying negatively charged proteoglycan matrix of the neutrophil granules in which the enzyme is stored. PMID- 2911586 TI - Submission of sequences. PMID- 2911585 TI - Heme oxygenase is the major 32-kDa stress protein induced in human skin fibroblasts by UVA radiation, hydrogen peroxide, and sodium arsenite. AB - We have shown that UVA (320-380 nm) radiation, hydrogen peroxide, and sodium arsenite induce a stress protein of approximately 32 kDa in human skin fibroblasts. The synthesis and cloning of cDNA from arsenite-induced mRNA populations have now allowed us to unequivocally identify the 32-kDa protein as heme oxygenase. By mRNA analysis we have shown that the heme oxygenase gene is also induced in cultured human skin fibroblasts by UVA radiation, hydrogen peroxide, cadmium chloride, iodoacetamide, and menadione. The known antioxidant properties of heme catabolites taken together with the observation of a high level of induction of the enzyme in cells from an organ not involved in hemoglobin breakdown strongly supports the proposal that the induction of heme oxygenase may be a general response to oxidant stress and constitutes an important cellular defense mechanism against oxidative damage. PMID- 2911587 TI - Submission of data to GenBank. PMID- 2911588 TI - Complete assignment of neurophysin disulfides indicates pairing in two separate domains. AB - The pairing of the 14 half-cystine residues of bovine neurophysin was established by sequential proteolytic digestion. Purified released peptides and the residual disulfide-linked core were monitored at each step by use of amino acid analysis, gas-phase sequencing, and mass spectrometry. The approach included application of gas-phase sequencing to assign disulfide pairs in peptides containing multiple disulfides. The results demonstrate that neurophysin disulfides are paired in two distinct domains--an NH2 domain (residues 10-54) containing four disulfides and a COOH domain (residues 61-85) containing three disulfides. The specific disulfide bridges are Cys-10 to Cys-54, Cys-13 to Cys-27, Cys-21 to Cys-44, Cys-28 to Cys 34, Cys-61 to Cys-73, Cys-74 to Cys-79, and Cys-67 to Cys-85. The results place the internally duplicated segments of neurophysin (residues 12-31 and 60-77) in separate domains. Disulfide-pairing patterns within each domain are homologous with the exception of the Cys-10 to Cys-54 bond, which is unique to the NH2 domain and which links the two ends of this domain together. The potential role of the Cys-10 to Cys-54 bond in organizing the hormone-binding site is discussed. PMID- 2911589 TI - Identical structural changes in inherited albumin variants from different populations. AB - Alloalbuminemia is rare and has a cumulative frequency of only approximately 1 in 3,000 in Europeans and Japanese. The worldwide ethnic and geographic distribution of certain albumin genetic variants appears to be nonrandom. Moreover, we have found that structurally identical variants may occur at different frequencies in ethnically distinct populations, presumably owing to independent mutations. In this study, albumin B and two types of proalbumins, which as a group are the most common European albumin variants, have also been found in Asians. We have identified the amino acid substitution characteristic of albumin B (glutamic acid ---lysine at position 570) in alloalbumins from six unrelated individuals of five different European descents and also in two Japanese and one Cambodian. The two types of proalbumins most common in Europe (Lille type, arginine----histidine at position -2; Christchurch type, arginine----glutamic acid at position -1) also occur in Japan. These results provide evidence for independent mutations at single sites in the albumin genome. The clustering of these and of several other amino acid exchanges in certain regions of the albumin molecule suggests two possibilities: that certain sites are hypermutable or that mutants involving certain sites are more subject to selection than mutants involving others. PMID- 2911590 TI - Analysis of the sequence-specific interactions between Cro repressor and operator DNA by systematic base substitution experiments. AB - We measured quantitatively the binding affinities of purified Cro repressor to the chemically synthesized wild-type and mutant OR1 operators, consisting of all three possible base-pair substitutions and of thymine to uracil substitutions at each base-pair position of the 17-base-pair operator sequence. The sequence specific interactions between Cro repressor and the operator DNA occur at the symmetrically disposed outer 7-base-pair positions of each half operator and at the central base-pair position. The binding of Cro is almost symmetrical with respect to the pseudo-twofold symmetry of the binding site. The binding free energy changes calculated from the affinity changes are mostly additive for specific Cro binding. Also the binding affinities of Cro to the operators or any other DNA sequences can be predicted by simple addition of free energy changes of single base substitutions. We isolated cro mutants by site-directed mutagenesis and studied their DNA binding to the wild-type and base-substituted mutant operators. The sequence-specific contacts derived from such studies are significantly different from the models proposed by Ohlendorf et al. [Ohlendorf, D. H., Anderson, W. F., Takeda, Y. & Matthews, B. W. (1982) Nature (London) 298, 719-723] and by Hochschild et al. [Hochschild, A., Douhan, J., III, & Ptashne, M. (1986) Cell 47, 807-816]. PMID- 2911591 TI - ATP stimulates Ca2+ uptake and increases the free Ca2+ concentration in isolated rat liver nuclei. AB - Addition of ATP to a highly purified fraction of rat liver nuclei incubated with submicromolar concentrations of Ca2+ and trace amounts of 45Ca2+ resulted in the rapid accumulation of 45Ca2+ in the nuclei. This was associated with an increase in intranuclear free Ca2+ concentration as measured with the fluorescent dye 1-[2 (5-carboxyoxazol-2-yl)-6-aminobenzofuran-5-oxy]-2-(2'-a mino-5'- methylphenoxy)ethane-N,N,N',N'-tetraacetic acid (fura-2). Inhibitors of microsomal and mitochondrial Ca2+ translocases had no effect on nuclear Ca2+ sequestration, indicating that it was distinct from previously known intracellular Ca2+-transporting systems. Ca2+ uptake and the associated increase in intranuclear free Ca2+ concentration were prevented by calmidazolium, a potent calmodulin antagonist. Partial characterization of the ATP-stimulated nuclear Ca2+ uptake showed that maximal rates of Ca2+ uptake and increase in intranuclear free Ca2+ level occurred at concentrations of Ca2+ normally present in the cytosol of mammalian cells. Together, these results show that a distinct, ATP- and calmodulin-dependent Ca2+ uptake system exists in liver nuclei. This system may play an important role in the regulation of intranuclear Ca2+-dependent processes. PMID- 2911592 TI - Mitochondrial damage in muscle occurs after marked depletion of glutathione and is prevented by giving glutathione monoester. AB - Skeletal muscle degeneration associated with mitochondrial damage was found after marked depletion of glutathione produced by administration to mice of buthionine sulfoximine, an irreversible inhibitor of gamma-glutamylcysteine synthetase. No mitochondrial damage was found in heart. These studies show that in the absence of applied stress (such as ischemia, drug toxicity), very marked depletion (to approximately 3% of the controls) of glutathione must occur before skeletal muscle mitochondria are affected and thus suggest that muscle has a large excess of glutathione. Depletion of glutathione followed a biphasic pattern in skeletal muscle and heart, probably reflecting, in the slow phase, loss of glutathione from mitochondria. Skeletal muscle degeneration did not occur when glutathione monoisopropyl ester was given together with buthionine sulfoximine; it did occur, however, when glutathione was given together with buthionine sulfoximine. Administration of the glutathione monoester (but not of glutathione) prevented the marked decline of mitochondrial glutathione produced by buthionine sulfoximine in skeletal muscle and increased the level of glutathione in heart mitochondria to values higher than the controls. The findings suggest that glutathione monoesters may be useful agents for protection of heart and skeletal muscle against toxicity. PMID- 2911593 TI - Expression of apolipoprotein B mRNAs encoding higher- and lower-molecular weight isoproteins in rat liver and intestine. AB - Two B apolipoproteins (apo) are present in human plasma, designated apoB-100 and apoB-48, and represent translational products from mature apoB mRNAs that differ by a single base. Either the glutamine codon encoded by the single-copy apoB gene at nucleotide 6666 is transcribed and translated to produce apoB-100 or an RNA editing mechanism substitutes a uracil for cytosine, altering this glutamine codon (CAA) to a stop codon (UAA), prematurely terminating translation to produce apoB-48. In the present report, editing of rat apoB transcripts was evaluated by amplification of RNA with the polymerase chain reaction by use of primers based on the apoB cDNA cloned from a rat liver cDNA library. The combined results of this study show that (i) a single copy of the apoB gene exists in the rat; (ii) the rat apoB gene encodes only the glutamine codon for the synthesis of apoB of higher molecular weight (apoBH); (iii) rat apoB transcripts undergo RNA editing; (iv) apoBH and apoB of lower molecular weight (apoBL) in the rat represent structural equivalents of apoB-100 and apoB-48 in humans, respectively; (v) RNA editing occurs in both the liver and intestine of the rat; (vi) rat hepatic apoB RNA is more extensively edited than is human hepatic apoB RNA, which is consistent with the marked increase in apoBL secretion by the rat liver when compared with human; and (vii) the definitive identification of apoBH mRNA as well as apoBL mRNA in the rat intestine provides a mechanism for the biosynthesis of both apoBH and apoBL by the rat intestine. PMID- 2911594 TI - Creation of phosphorylation sites in proteins: construction of a phosphorylatable human interferon alpha. AB - A phosphorylation site was introduced into human interferon alpha A (IFN-alpha A) by site-specific mutation of the coding sequence. Three slightly different phosphorylation sites were created by using the predicted amino acid consensus sequences for phosphorylation by the cAMP-dependent protein kinase. The resultant modified interferons (IFN-alpha A-P) were expressed in Escherichia coli and purified. The purified proteins exhibit antiviral activity on bovine and human cells similar to that of the unmodified IFN-alpha A. The IFN-alpha A-P proteins can be phosphorylated by the catalytic subunit of cAMP-dependent protein kinase with [gamma-32P]ATP to high specific activity (2000-5000 Ci/mmol; 1 Ci = 37 GBq) with retention of biological activity. The 32P-labeled IFN-alpha A-P proteins bind to cells and can be covalently bound to the IFN-alpha/beta receptor with a bifunctional reagent as can human IFN-alpha A. The introduction of phosphorylation sites into proteins provides a procedure to prepare a large variety of radioactive proteins for research and clinical use. PMID- 2911595 TI - Behavioral evolution and biocultural games: vertical cultural transmission. AB - We consider an evolutionary game model in which strategies are transmitted culturally from parents to offspring rather than inherited biologically. Our analysis yields two noteworthy results. First, biocultural games show a greater diversity of dynamical behaviors than their purely biological counterparts, including multiple fully polymorphic equilibria. Second, biocultural games on average exhibit greater equilibrium strategy diversity because of the countervailing influences of cultural transmission and natural selection. Therefore, knowledge of a strategy's influence on Darwinian fitness is not sufficient to infer the evolutionary consequences of biocultural games. Further, our results suggest that cultural transmission in the presence of natural selection may be an important mechanism maintaining behavioral diversity in natural populations. PMID- 2911596 TI - Three-dimensional structure of Fab R19.9, a monoclonal murine antibody specific for the p-azobenzenearsonate group. AB - The crystal structure of Fab R19.9, derived from an anti-p-azobenzenearsonate monoclonal antibody, has been determined and refined to 2.8-A resolution by x-ray crystallographic techniques. Monoclonal antibody R19.9 (IgG2b kappa) shares some idiotopes with a major idiotype (CRIA) associated with A/J anti-p azobenzenearsonate antibodies. The amino acid sequences of the variable (V) parts of the heavy (VH) and light (VL) polypeptide chains of monoclonal antibody R19.9 were determined through nucleotide sequencing of their mRNAs. The VL region is very similar to that of CRIA-positive anti-p-azobenzenearsonate antibodies as is VH, except for its third complementarity-determining region, which is three amino acids longer; it makes a loop, unique to R19.9, that protrudes into the solvent. A large number of tyrosine residues in the complementarity-determining region of VH and VL, with their side chains pointing towards the solvent, may have an important function in antigen binding. PMID- 2911597 TI - Increased clearance of plasma cholesterol after injection of apolipoprotein E into Watanabe heritable hyperlipidemic rabbits. AB - Apolipoprotein E (apoE) is known to play an important role in lipoprotein metabolism. We have studied the effect of apoE on the metabolism of plasma cholesterol by injecting apoE intravenously into rabbits deficient in low density lipoprotein receptors [Watanabe heritable hyperlipidemic (WHHL) rabbits]. Approximately 30 mg of apoE was injected per rabbit; a total of five WHHL rabbits were used. One hour later, plasma cholesterol levels fell 8.3% (from 488 +/- 192 to 446 +/- 174 mg/dl). After 3 hr, cholesterol levels had fallen by 19% (to 392 +/- 152 mg/dl). The reduced levels were maintained for at least 8 hr after injection of apoE. Cholesterol in very low density lipoproteins (VLDLs) and intermediate density lipoproteins fell rapidly during the first 2 hr after injection, followed by a reduction in the low density lipoprotein cholesterol level. Changes in apolipoprotein B levels in each lipoprotein fraction were very similar to those of cholesterol. Plasma apoE levels 3 min after injection were elevated 3-fold to 22.8 +/- 6.3 mg/dl and returned to initial levels 8 hr after injection. The rate of removal of intravenously injected 125I-labeled VLDL that had been incubated with apoE was 3-fold higher than that of unmodified VLDL. From these results, we conclude that the injected apoE is incorporated into VLDLs and that VLDL particles carrying more apoE are removed from the blood more rapidly, resulting in reduced formation of low density lipoprotein and lowered cholesterol levels. PMID- 2911598 TI - Evidence for increased in vivo mutation and somatic recombination in Bloom's syndrome. AB - The glycophorin A assay was used to estimate the frequency of mutations that accumulate in vivo in somatic cells of persons with Bloom's syndrome (BS). This assay measures the frequency in persons of blood type MN of variant erythrocytes that lack the expression of one allelic form of glycophorin A, presumably due to mutational or recombinational events in erythroid precursor cells. Samples of blood from persons with BS showed dramatic 50- to 100-fold increases in the frequency of variants of three types, those with a hemizygous phenotype, those with a homozygous phenotype, and those with what appears to be partial loss of the expression of one locus. The high frequency of homozygous variants, genetic evidence for altered allelic segregation of a specific biochemical locus, provides evidence for increased somatic crossing-over in vivo in BS. An increased generation of functional hemizygosity and homozygosity in their somatic cells may play an important role in the extreme cancer risk of persons with BS. PMID- 2911599 TI - De novo amplification within a "silent" human cholinesterase gene in a family subjected to prolonged exposure to organophosphorous insecticides. AB - A 100-fold DNA amplification in the CHE gene, coding for serum butyrylcholinesterase (BtChoEase), was found in a farmer expressing the "silent" CHE phenotype. Individuals homozygous for this gene display a defective serum BtChoEase and are particularly vulnerable to poisoning by agricultural organophosphorous insecticides, to which all members of this family had long been exposed. DNA blot hybridization with regional BtChoEase cDNA probes suggested that the amplification was most intense in regions encoding central sequences within BtChoEase cDNA, whereas distal sequences were amplified to a much lower extent. This is in agreement with the "onion skin" model, based on amplification of genes in cultured cells and primary tumors. The amplification was absent in the grandparents but present at the same extent in one of their sons and in a grandson, with similar DNA blot hybridization patterns. In situ hybridization experiments localized the amplified sequences to the long arm of chromosome 3, close to the site where we previously mapped the CHE gene. Altogether, these observations suggest that the initial amplification event occurred early in embryogenesis, spermatogenesis, or oogenesis, where the CHE gene is intensely active and where cholinergic functioning was indicated to be physiologically necessary. Our findings demonstrate a de novo amplification in apparently healthy individuals within an autosomal gene producing a target protein to an inhibitor. Its occurrence in two generations from a family under prolonged exposure to parathion indicates that organophosphorous poisons may be implicated in previously unforeseen long-term ecological effects. PMID- 2911600 TI - Retinal dopamine and form-deprivation myopia. AB - Investigation of retinal neurochemistry in a well-defined chick model of form deprivation myopia indicated that dopamine and its metabolite 3,4 dihydroxyphenylacetic acid are reduced in myopic as compared to control eyes. The reduction in retinal dopamine is evident only during light adaptation and is accompanied by a decreased rate of dopamine biosynthesis. To test whether the alteration in dopamine metabolism is related to eye growth, agents known to interact with dopamine receptors were administered locally to deprived eyes. Remarkably, the expected growth in the axial dimension was reduced, while that in the equatorial dimension was not. Therefore retinal dopamine may participate in the pathway linking visual experience and the postnatal regulation of the eye's growth in the axial dimension. The mechanism for control of chick eye growth in the equatorial dimension remains unknown. PMID- 2911601 TI - Identification of the convulsant opiate thebaine in mammalian brain. AB - The convulsant opiate thebaine, an intermediate of morphine biosynthesis, was purified from bovine brain to homogeneity by gel filtration and high-performance liquid chromatography (HPLC) monitored by a radioimmunoassay. The immunoreactive material behaved identically to standard thebaine in two HPLC systems and was confirmed to be thebaine by combined gas chromatography/mass spectrometry. To our knowledge, the presence of thebaine in mammalian tissue has not been demonstrated previously. Codeine and morphine were also found to exist in ovine brain. The presence of thebaine in ovine brain provides strong evidence that morphine and codeine, in various mammalian tissues, are of endogenous origin and actually biosynthesized from a precursor. PMID- 2911602 TI - Angiotensin II receptors in paraventricular nucleus, subfornical organ, and pituitary gland of hypophysectomized, adrenalectomized, and vasopressin-deficient rats. AB - Angiotensin II has been implicated in the regulation of adrenocorticotropin and vasopressin secretion. Angiotensin II may influence the secretion of these hormones either directly at the pituitary gland or by increasing corticotropin releasing hormone or vasopressin release from cells that are located in the paraventricular hypothalamic nucleus. Pituitary hormone release may also be influenced by circulating angiotensin II through receptors outside the blood brain barrier in the subfornical organ. We have used alterations in angiotensin II receptors in hypophysectomized, adrenalectomized, and vasopressin-deficient Brattleboro rats as indicators of the activity of angiotensin II in the regulation of adrenocorticotropin and vasopressin secretion. Angiotensin receptor number in the paraventricular nucleus and the subfornical organ, but not in the anterior pituitary gland, was significantly decreased by adrenalectomy, and this effect was reversed by corticoids. Vasopressin deficiency decreased angiotensin receptors in the subfornical organ and increased them in the anterior pituitary gland but did not affect angiotensin II binding in either magnocellular or parvocellular subnucleus of the paraventricular nucleus. Our results suggest that angiotensin II may have a corticoid-dependent role in the regulation of corticotropin-releasing hormone secretion, which could be important in the adaptation to elevated corticosterone secretion in stress. PMID- 2911605 TI - Swimming-induced suppression of rat pineal melatonin is prevented by pretreatment with calcium channel blockers. AB - Young adult male rats were treated with isoproterenol during the day to induce high levels of pineal N-acetyltransferase (NAT) activity and melatonin. Roughly 2 hr later when pineal NAT activity and melatonin levels were elevated, animals were given either an injection of a calcium channel blocker, i.e., either nifedipine or verapamil, or diluent. The rats were then forced to swim for 10 min in room temperature (22 degrees C) water. Fifteen minutes after swimming onset, pineal glands were collected for measurement of NAT activity and melatonin. Swimming caused a dramatic reduction in pineal melatonin content without influencing NAT activity. Nifedipine substantially and verapamil completely blocked the drop in pineal melatonin levels due to swimming without influencing NAT activity. The results suggest that calcium may be somehow directly or indirectly involved in melatonin release from the rat pineal gland. PMID- 2911606 TI - Intestinal uptake of fluorescent microspheres in young and aged mice. AB - Rhodamine B-labeled synthetic latex particles (microspheres), 1.8 micron in diameter, were administered by gavage 5 days per week to young (24 days) and aged (18 months) mice. After 25 days (19 gavages), the particles were assayed in solubilized tissues by depositing them on filters and counting under fluorescence microscopy. Aged mice exhibited significantly more fluorescent particle accumulation in Peyer's patches but significantly less in lungs than young mice. Mesenteric lymph nodes and Peyer's patch-free intestinal segments contained measurable latex, but differences between young and aged animals were not significant. Liver contained only trace amounts of latex, and spleen and kidney were latex free in both young and aged animals. Nonquantitative observations on KOH-glycerol-cleared whole Peyer's patches and slices of liver, lung, and mesenteric lymph node were similar. PMID- 2911603 TI - Peripheral nerve damage facilitates functional innervation of brain grafts in adult sensory cortex. AB - The neural pathways that relay information from cutaneous receptors to the cortex provide the somatic sensory information needed for cortical function. The last sensory relay neurons in this pathway have cell bodies in the thalamus and axons that synapse on neurons in the somatosensory cortex. After cortical lesions that damage mature thalamocortical fibers in the somatosensory cortex, we have attempted to reestablish somatosensory cortical function by grafting embryonic neocortical cells into the lesioned area. Such grafts survive in adult host animals but are not innervated by thalamic neurons, and consequently the grafted neurons show little if any spontaneous activity and no responses to cutaneous stimuli. We have reported that transection of peripheral sensory nerves prior to grafting "conditions" or "primes" the thalamic neurons in the ventrobasal complex so that they extend axons into grafts subsequently placed in the cortical domain of the cut nerve. In this report we present evidence that the ingrowth of ventrobasal fibers leads to graft neurons that become functionally integrated into the sensory circuitry of the host brain. Specifically, the conditioning lesions made prior to grafting produce graft neurons that are spontaneously active and can be driven by natural activation of cutaneous receptors or electrical stimulation of the transected nerve after it regenerates. Furthermore, oxidative metabolism in these grafts reaches levels that are comparable to normal cortex, whereas without prior nerve cut, oxidative metabolism is abnormally low in neocortical grafts. We conclude that damage to the sensory periphery transsynaptically stimulates reorganization of sensory pathways through mechanisms that include axonal elongation and functional synaptogenesis. PMID- 2911604 TI - Alternative mRNA splicing generates multiple forms of peptidyl-glycine alpha amidating monooxygenase in rat atrium. AB - Peptidyl-glycine alpha-amidating monooxygenase (PAM; EC 1.14.17.3) catalyzes the conversion of a variety of glycine-extended peptides into biologically active alpha-amidated product peptides in a reaction dependent on copper, ascorbate, and molecular oxygen. We have isolated and sequenced cDNAs representing the two major classes of PAM mRNA in the adult rat heart atrium. The two types of cDNA, rPAM-1 and rPAM-2, are identical except for the deletion of a 315-base-pair segment within the protein coding region in rPAM-2, suggesting that rPAM-1 and rPAM-2 arise by alternative splicing. Northern analysis using a cDNA probe derived from within the 315-base-pair region deleted in rPAM-2 visualized the larger of the PAM mRNAs in adult rat atrium and not the smaller, indicating that the presence or absence of this 315-nucleotide segment is a major feature distinguishing the two size forms of PAM mRNA. The 105 amino acid segment that distinguishes the two forms of atrial PAM contains a consensus N-glycosylation site and a paired basic amino acid site of potential importance in endoproteolytic processing. Comparison of the nucleotide sequences of rat, frog, and bovine PAM cDNAs reveals an extremely well conserved segment in the 3' untranslated region. The high degree of conservation in amino acid sequence throughout the catalytic, intragranular, and cytoplasmic domains of rat atrium, bovine pituitary, and frog skin PAM suggests that both the catalytic and noncatalytic domains of the protein subserve important functions. PMID- 2911607 TI - Effect of acute and chronic vanadate administration on sugar transport in rat jejunum. AB - Vanadate is known to have an insulin-like action which stimulates sugar transport in some systems like adipocytes and muscle cells, but in other systems it inhibits sugar transport by decreasing the activity of (Na+ +K+)-ATPase. To evaluate whether these two opposing actions may influence sugar transport across the intestine, we studied the effects of acute and chronic vanadate administration on the uptake of glucose, galactose, and 3-O-methylglucose in isolated rat intestinal cells. The sugar uptake measurements were also coupled by determinations of rubidium-86 uptake as a measure of the activity of the Na-K pump. Both acute and chronic vanadate administration reduced rubidium uptake by the cells but the reduction did not uniformly influence the uptake of the three sugars in question which were stimulated by the acute exposure of the cells to vanadate. Glucose uptake was also stimulated by chronic vanadate administration, but the uptakes of galactose and 3-O-methylglucose were respectively unaffected or inhibited by chronic vanadate. The findings suggest that the effect of vanadate on sugar transport is dependent on the net difference between two actions of vanadate: (i) stimulation of a receptor site (possibly an insulin receptor site) in the intestinal cell membrane and (ii) inhibition of the Na-K pump. During acute vanadate exposure, the stimulation of the receptor site was very likely a dominant feature which overwhelms the inhibition of the pump. Chronic exposure to vanadate led, on the other hand, to only a limited degree of stimulation of the receptor site and the inhibition of the Na-K pump became evident in the uptake measurements of galactose and 3-O-methyl-glucose. Glucose uptake, however, was stimulated by chronic vanadate ingestion due, very likely, to an increase in the metabolism of this sugar which occurred only with prolonged exposure of the rat intestine to vanadate. PMID- 2911608 TI - Lysozyme-induced inhibition of the lymphocyte response to mitogenic lectins. AB - Both human lysozyme (HL) and hen egg white lysozyme (HEWL) inhibited the proliferative response of peripheral blood lymphocytes to T cell mitogens such as the lectins phytohemagglutinin and concanavalin A. This inhibition was observed both when HL or HEWL was added to the lymphocyte cultures in combination with phytohemagglutinin or concanavalin A and when lymphocytes were pretreated with either lysozyme and extensively washed prior to culture with mitogens. Under both conditions, the effects were strictly dose dependent; the lysozyme concentrations yielding maximal inhibitory effect were 5 micrograms/ml for HL and 1 microgram/ml for HEWL, while both lower and higher concentrations were less effective. Specific antilysozyme rabbit sera completely prevented the inhibitory effects of both HL and HEWL on the proliferative response of lymphocytes to phytohemagglutin or concanavalin A. Chitotriose (a lysozyme inhibitor) caused a strong reduction in the inhibitory effects of the two lysozymes on the lymphocyte response to either lectin. HL and HEWL also were found to markedly inhibit the polyclonal B cell proliferation and differentiation induced by pokeweed mitogen and T cells. A less marked inhibition was also obtained when T cells, but not B cells, were pretreated with HL or HEWL. Again, as in the experiments with T cell mitogens, the effects were dose dependent and 5 micrograms/ml HL and 1 microgram/ml HEWL proved to be the most effective concentrations. The possible mechanisms by which lysozyme inhibits the lymphocyte response to mitogenic lectins are considered and discussed. The enzymatic activity seemed to perform an essential function, as shown by the loss of effect when the heat- or trypsin-inactivated lysozymes were used and by the fact that only the enzymatically active compound, among certain semisynthetic derivatives of HEWL, inhibited the lymphocyte response to the mitogens. However, the cationic properties of the lysozyme molecule appeared to be essential too, since enzymes with a similar specificity of action showed effects similar to those observed with HL or HEWL only when they carried a strong positive charge. It is suggested that lysozyme, which is naturally secreted by monocytes and macrophages, might interact with lymphocyte surface receptor sites and participate in the complex mononuclear phagocyte-lymphocyte interactions and in the modulation of lymphocyte activation. PMID- 2911609 TI - Effect of maternal glucose concentration on uteroplacental glucose consumption and transfer in pregnant sheep. AB - The present study was designed to measure the relationships between maternal arterial glucose concentration [( GI]A) and fetal arterial glucose concentration [( GI]a), uteroplacental glucose consumption (UPGC), and the rate of uteroplacental glucose transfer to the fetus (UPGT) in pregnant sheep in late gestation. [GI]A was controlled by a glucose clamp technique and the glucose flux rates of the uteroplacenta were quantified by the Fick principle. [GI]A varied from 1.81 to 154.7 mg/dl; [GI]a was directly related to [GI]A: [GI]a = 0.374 [GI]A + 1.81, r = 0.873, P less than 0.001. Fetal arterial blood oxygen content decreased with [GI]A (P less than 0.05) and fetal arterial blood lactate concentration increased with [GI]A (P less than 0.001). There was no significant effect of [GI]A on the rates of uteroplacental lactate production, uteroplacental oxygen consumption, fetal oxygen consumption, or uterine or umbilical blood flow. Both UPGC and UPGT were directly related to [GI]A: UPGC = -2.221 x 10(-3) chi 2 + 0.646 x -6.016, r = 0.80; UPGT = -1.208 x 10(-3) chi 2 + 0.405 x -2.416, r = 0.90. UPGC and UPGT were approximately parallel over the range of [GI]A studied (UPGC = 1.19 UPGT + 3.79, r = 0.764). These results demonstrate the importance of UPGC to maternal-fetal glucose homeostasis and indicate that factors regulating uteroplacental glucose consumption and transfer to the fetus become limiting at comparable levels of [GI]A and [GI]a. The estimated kinetic constants for UPGC represent the metabolism of glucose by the uteroplacental tissues, but the estimated kinetic constants for UPGT represent the metabolism of glucose by the fetus as well as the transfer of glucose by the uteroplacenta to the fetus. PMID- 2911610 TI - Oxidative metabolism of cocaine: comparison of brain and liver. AB - Norcocaine (NC) and N-hydroxynorcocaine (NHNC), products of the oxidative metabolism of cocaine, were examined in plasma, brain, and liver of mice injected intraperitoneally with cocaine. Plasma levels of NHNC were altered in vivo by inhibiting esterase activity with diazinon and chloral hydrate or activating esterase activity with phenobarbital, and activating the microsomal P-450 system with phenobarbital. Changes in plasma concentrations of NHNC resulted in similar changes in brain, which were often different from those in liver. After intracisternal administration of cocaine to mice, no appreciable amount of NC or NHNC could be detected in brain; the same results were obtained upon intracisternal and intraventricular administration to rats. Microsomal preparations from mouse brain were found to be considerably less active than those from liver in converting NC to NHNC. We conclude that the cerebral oxidative metabolism of cocaine is not appreciable and that most of the NC and NHNC found in the brain after systemic cocaine administration is derived from plasma rather than formed centrally by brain microsomal enzymes. PMID- 2911611 TI - Evaluation of an anti-inflammatory factor derived from hyperimmunized cows. AB - An anti-inflammatory factor isolated from milk of hyperimmunized cows was analyzed in vitro and in vivo. Macrophages collected from lacteal secretions of a unimmunized nonlactating cow showed increased ability to kill phagocytosed Staphylococcus aureus when incubated with the anti-inflammatory factor. Mice injected intraperitoneally with 10 mg/kg of anti-inflammatory factor demonstrated an increased LD50 to S. aureus when challenged intraperitoneally. Injected mice also demonstrated significantly (P less than 0.05) less mammary inflammation and involution and increased clearance of S. aureus when challenged intramammarily. Quantitative histologic analysis of mammary tissues from mice injected with anti inflammatory factor demonstrated significantly (P less than 0.05) more lumen, less interalveolar connective tissue, and less leukocytic infiltration compared with control mice. Mammary glands of mice injected with anti-inflammatory factor and challenged with S. aureus also contained fewer colony-forming units than control mice. The product appeared to exert its effect on the nonspecific defense system via modulation of leukocyte function. PMID- 2911612 TI - Composition of proteoglycans in the aortas of copper-deficient rats. AB - Copper deficiency adversely affects the extracellular matrix of the arterial wall, leading to cardiovascular lesions. To study the lesions resulting from copper deficiency, the composition of proteoglycans from aortas of copper deficient rats was compared with proteoglycans of aortas from copper-supplemented rats. Copper deficiency in rats was verified by copper levels in adrenal glands (mean +/- SE, 0.37 +/- 0.07 vs 1.03 +/- 0.17 micrograms/g wet wt in supplemented rats). The proteoglycans were isolated from the aorta by extraction with 4 M guanidine-HCl and by digestion of the tissue with elastase. The proteoglycans were purified by CsCl isopycnic centrifugation and fractionated by gel filtration. The fractions were characterized for molecular size and glycosaminoglycan composition. Total uronate in the aortas from copper-deficient rats was 25% greater than in aortas from copper-supplemented rats, and the proteoglycans from copper-deficient rat aortas were of greater molecular size. Among the glycosaminoglycans the concentration (microgram/mg tissue) of isomeric chondroitin sulfates, particularly dermatan sulfate, was greater in copper deficient animals than in copper-supplemented animals. These observations are similar to earlier findings in experimental atherosclerosis and to a response of cardiovascular connective tissue to injury. PMID- 2911613 TI - Pelvic exercise and gait in hemiplegia. AB - The purpose of this study was to describe and compare the gait of 20 patients with hemiplegia secondary to cerebrovascular accident (CVA) before and after a treatment regimen of resisted pelvic motions. Ten women and 10 men were studied, with a mean age of 48 years and a mean duration post-CVA of two months. Nine subjects (45%) were right hemiplegic, and 11 subjects (55%) were left hemiplegic. Treatment consisted of four sets of five repetitions each of manually resisted pelvic anterior-elevation and posterior-depression movements on the involved side. An insole footswitch system, knee electrogoniometer, and force walking aid were used in gait analysis performed before treatment, immediately after treatment (posttest 1), and 30 minutes after treatment (posttest 2). Results showed significant overall improvement in gait in posttest 1 (p less than .005) compared with the pretest. This improvement, however, was not maintained in posttest 2. Ten patients improved overall in posttest 1; only 4 patients also showed improvement in posttest 2. The major improvements seen immediately after treatment were observed in stance stability and limb advancement in the involved limb. More research is needed to identify an optimum treatment with carry-over using this technique. PMID- 2911614 TI - Salary, education, and managerial-level differences of physical therapists in Maryland. AB - The purpose of this study was to determine whether differences existed between a random sample of male and female physical therapists on selected factors. These factors included salary, managerial level, number of courses taken in management or administration, years of work experience in physical therapy, and years of seniority in an organization. A self-reported questionnaire was sent to 400 licensed physical therapists in Maryland who were also American Physical Therapy Association members. Data were analyzed on the 244 respondents using chi-square tests, t tests, and critical ratios. Results showed that female physical therapists, when employed full time in Maryland as department managers, on average, earned significantly less than their male counterparts. A significant difference existed between male and female department managers for full-time work experience in physical therapy. Neither the number of management courses taken nor seniority in an organization were significantly different for male and female physical therapists, regardless of managerial level. Conclusions were that differences existed on several factors between male and female physical therapy department managers and that schools preparing physical therapists for entry into the profession should assess the need for management preparation. PMID- 2911615 TI - Impact of physical therapy weekend coverage on length of stay in an acute care community hospital. AB - This study compares the length of hospital stay of a group of patients treated in a community hospital during a period of five-day-a-week physical therapy coverage with the length of stay of a similar patient group treated during a period of seven-day-a-week physical therapy coverage. Comparisons of length of stay were made between the two groups and between subgroups based on diagnosis (stroke or orthopedic disorder) and surgical versus nonsurgical status. Multiple regression analysis was used to control for other factors influencing length of hospital stay. The mean length of stay was shorter for the seven-day-a-week group, and in a few subgroups the difference in length of stay was statistically significant. The results of this study suggest that weekend physical therapy may help reduce length of hospital stay. This finding should interest individuals concerned with the cost-effective use of physical therapy, especially under hospital reimbursement systems such as the Medicare diagnosis-related group. PMID- 2911616 TI - Resistance exercise effects on aging skeletal muscle in rats. AB - The purpose of this study was to determine whether a resistance exercise program could be initiated successfully at progressively older ages in rats. Forty female Sprague-Dawley rats, 7 to 10 in each age group (21, 24, 27, and 30 months, respectively), performed 60 manually resisted chin-ups (three sets of 10 repetitions each twice daily) for three months. Twenty controls, 5 in each age group, were followed for three months but not exercised. Before the experimental period began, the rats' left palmaris longus (PL) muscle was removed, weighed, frozen, sectioned, and stained. After the three-month period, the right PL muscle was removed and the same tissue preparation procedure was followed. Muscle fiber types I and II were identified on photomicrographs, and areas of each fiber type measured. No significant change in muscle wet weight or fiber size occurred in the controls. Significant increases (p less than .01) in type II muscle fiber area occurred for the 21-, 24-, and 30-month-old rats that exercised. No histological evidence of exercise-related harm was observed in tissues from exercised rats. Results indicate that resistance exercise can be introduced successfully to an aging or aged rat without doing harm. Studies are needed to determine whether similar results can be achieved for elderly humans. PMID- 2911617 TI - Relationship between multiple predictor variables and normal knee torque production. AB - The purpose of this study was to develop predictive models relating isokinetic knee testing performance to anthropometric and demographic variables. The subjects were 134 healthy volunteers (70 female, 64 male) between the ages of 10 and 80 years. The investigators measured subjects' peak knee flexion and extension torque production at two angular velocities. Stepwise regression analyses were used to examine the relationship between each torque-dependent variable and the following potential predictor variables: age, sex, side of lower extremity dominance, height, weight, percentage of body fat, and thigh girth. The investigators generated two sets of models designed to predict preinjury knee strength. Clinicians can use one set of models by assessing predictor variables before or immediately following injury. The second set of models involves the assessment of predictor variables postinjury, excluding an assessment of percentage of body fat and thigh girth. The results indicated that peak knee torque production can be predicted with statistically significant accuracy (multiple R = .78-.87). The predictive models generated in this study can be used to establish muscle strength goals for patient rehabilitative programs. PMID- 2911618 TI - Description of adult rolling movements and hypothesis of developmental sequences. AB - Physical therapists frequently evaluate and teach patients to roll from a supine to a prone position. The purposes of this study were 1) to describe the rolling movements of adults and 2) to determine whether the movement patterns used to roll might represent different developmental steps within three body regions. Thirty-six healthy adult subjects were videotaped during 10 trials of rolling from a supine to a prone position. Written descriptions of each subject's movements were reduced to general categorical descriptions of movement patterns for three body regions (upper extremities, lower extremities, and head and trunk). Stage theory criteria were used in an attempt to order the movement patterns into developmental sequences. The most common combination of movement patterns was used to describe adults' rolling action. Although stage theory criteria were not met, developmental sequences of movement patterns were proposed for the three body regions. Subjects were quite variable in their rolling movements. The most common form of rolling occurred in less than 12% of the subjects' trials. The descriptions of adults' rolling action gathered in this study provide physical therapists with a variety of movement patterns for teaching patients to roll. PMID- 2911619 TI - Exercise programs for patients with post-polio syndrome: a case report. AB - Several authors have reported on post-polio syndrome, indicating a decline in muscle strength in individuals years after the onset of poliomyelitis. These reports include suggestions that strenuous exercise programs are contraindicated and may have deleterious effects for patients with post-polio syndrome. The purpose of this case study was to examine the effects of an aggressive, six-week isokinetic exercise program on a 59-year-old patient with post-polio syndrome. Peak torque values were assessed before and during the exercise program, and 6 and 22 weeks following cessation of the exercise program. The results indicate no deleterious effects secondary to the exercise program. The authors suggest future research strategies to investigate the efficacy of exercise programs for patients with post-polio syndrome. PMID- 2911620 TI - Cutaneous blood supply of the penis. AB - Twelve male cadaver specimens were injected with a latex solution to define the cutaneous blood supply of the penis. The cutaneous blood supply of the penile shaft is derived solely from a pair of axial arteries running in the dartos layer. Additional deep perforating arteries from the dorsal penile artery and corporal vessels supply the glans and subcoronal region. An understanding of this anatomy allows one to develop safely a variety of penile skin flaps for difficult reconstructive problems. PMID- 2911622 TI - Exogenous laminin induces regenerative changes in traumatized sciatic and optic nerve. AB - Laminin is an extracellular matrix component which can promote neuritic elongation in vitro and has been implicated in the promotion of nerve regeneration in vivo. The present study was undertaken to determine if implantation of Elvax pellets containing exogenous laminin distal to site of lesion could promote regenerative responses in vivo in the adult rat peripheral (sciatic) and central (optic) nerve. In peripheral nerve preparations, Elvax pellets containing laminin or collagen were assessed for their ability to "lure" transected axons into 5-mm-long silicone tubes. In optic nerve studies, laminin pellets were inserted distal to site of nerve crush, and the extent of axonal elongation 2.5 mm to the injury site was assessed. Laminin-containing pellets appeared to support appreciable axonal elongation in both systems. This effect was dose-dependent and not exerted by collagen pellets, substrate-free pellets, or pellets containing irradiated laminin. Collagen IV had some beneficial effect in peripheral, but not central, nerve preparations. PMID- 2911621 TI - Projection geometry and stress-reduction techniques in craniofacial surgery. AB - Since 1981, we have been able to modify the mathematical patterns of projection geometry to reshape the skull in craniofacial surgery. Unlike burring, morcellization, rotation, and plate switching, this technique actually changes the shape of individual sections of the skull by changing their radius of curvature. The technique is an adaptation of the principles used by engineers to build complex structures such as ships' hulls, airfoils, and domes. The result is a rigid form of the desired shape that becomes permanent with healing. This has several advantages: 1. An increase in the level of safety of craniofacial procedures for remodeling the skull. This is so because there is no need to dissect normal areas as in the standard plate-switching techniques. 2. Decreased operating room time. 3. An increased range of surgical manipulations. No longer is the surgeon limited to the shape of the material present. 4. Relief of edge pressure on the frontal lobes during scalp closure. 5. Creation of a solid bony form over which the pericranial scalp flap can be draped to form new layers of bone. PMID- 2911623 TI - The oculocardiac reflex in blepharoplasty surgery. AB - The oculocardiac reflex (OCR), a previously undescribed phenomenon in aesthetic blepharoplasty surgery, involves intraoperative bradycardia exceeding 10 percent of the preoperative heart rate or any dysrhythmia during ocular manipulation. It is a trigeminal-vagal-mediated reflex arc. The oculocardiac reflex was noted to occur in 25 of 100 patients (25 percent) undergoing blepharoplasty. A data sheet designed and distributed for use in the operating room identified a reflex-prone patient (RPP) as a young, anxious female, with a cardiac history, operated on under light anesthesia with aggressive fat pad resection. The oculocardiac reflex was more likely to occur in a reflex-prone patient during traction on the medial fat pads and in the left eye. Despite anticipating the fatigue phenomenon in those patients who exhibited a profound bradycardia (35 to 40 beats per minute), it was necessary to release traction in order to permit the heart rate to return to normal. Awareness and treatment of this potentially life-threatening oculocardiac reflex are necessary. Careful patient surveillance and monitoring are mandatory. PMID- 2911624 TI - The subcutaneous forehead lift. AB - A limited experience (27 patients, all female) is presented utilizing the subcutaneous approach to forehead lifting. This approach has been little utilized and has been condemned in the literature for being dangerous. However, no difficulties in wound healing or alopecia have been encountered, and the procedure has the advantages of more effectively removing the vertical and transverse wrinkles in the glabellar region, raising the brows, and preserving sensation to the scalp posterior to the incision. PMID- 2911625 TI - Anatomy of the buccal fat pad and its clinical significance. AB - Interest in the anatomy of the buccal fat pad was aroused by two clinical cases where the fat pad was involved by pathology. In one, there was an extensive lipoma of the buccal fat pad which had been unsuccessfully operated on on two previous occasions. The reason for the lack of success was incomplete removal of the fat pad. In the second case, there was an arteriovenous malformation involving the fat pad which necessitated complete removal. Fresh cadaver dissections were carried out to accurately determine the anatomy. Particular attention was paid to the temporal extension, since this area is frequently disregarded. PMID- 2911626 TI - Anatomy of the frontal branch of the facial nerve: the significance of the temporal fat pad. AB - The anatomy of the temporal region, with reference to the frontal branch of the facial nerve, was examined in 12 fresh cadaver dissections. In all dissections, the frontal branch traveled in a constant plane along the undersurface of the temporoparietal fascia and was quite superficial as it crossed the zygomatic arch. The deep temporal fascia and superficial temporal fat pad are anatomically important structures which adjoin the periosteum of the zygomatic arch and lie deep to the frontal nerve. Based on these relationships, a safe method of dissection within the temporal region is formulated. PMID- 2911627 TI - The prominent mandibular angle: preoperative management, operative technique, and results in 42 patients. AB - A prominent mandibular angle is considered to be unattractive in the Orient because it gives the face a square and muscular appearance. While described infrequently in the United States, this entity is commonly encountered in the Orient owing to different facial characteristics and different aesthetic sensibilities. We present a retrospective study of 42 female patients who presented requesting the reduction of a prominent mandibular angle for cosmetic reasons. We describe our approach, which utilizes formal planimetry, cephalometric tracings, and Panorex mandibular radiographs. We utilize the intraoral approach and use an oscillating saw to resect the predetermined segment of bone. In 18 of the 42 patients, we resected muscle as well. We also describe using the preauricular incision in a patient undergoing a concomitant rhytidectomy. Our cosmetic results have been generally satisfactory, with only one inaccurate osteotomy. We had three infections which resolved without sequelae. PMID- 2911628 TI - Plantar fibromatosis: an isolated disease. AB - Plantar fibromatosis is a relatively uncommon benign disease characterized by bilateral nodular thickening of the plantar fascia similar in appearance to the disease which occurs in the palm of the hand. Descriptions of plantar fibromatosis in the literature were usually included as a part of a syndrome described as ectopic diseases of Dupuytren. Isolated case reports have described Dupuytren-like contractures of the plantar fascia but often suggested a relationship with palmar lesions. We have recently treated four patients with isolated plantar fibromatosis without other stigmata of Dupuytren's disease. These patients were treated by removal of all the involved plantar fascia with a wide margin of normal-appearing fascia. PMID- 2911629 TI - Effect of a high-intensity static magnetic field on sciatic nerve regeneration in the rat. AB - The effect of a high-intensity static magnetic field on peripheral nerve regeneration is evaluated in rat sciatic nerve. Forty-four rats underwent sciatic nerve repair using polyethylene nerve guides. Postoperatively, the animals were exposed to a 1-tesla magnetic field for 12 hours per day for 4 weeks with appropriate controls. Our results demonstrate that a 1-tesla static magnetic field has no statistically significant effect on nerve regeneration as determined by myelinated axon counts and electrophysiologic studies. Also, the specific orientation of the sciatic nerve with respect to the magnetic field has no influence on axonal growth or nerve conduction. Periods of restraint of 12 hours per day for 4 weeks significantly inhibit weight gain but have no effect on peripheral nerve regeneration. PMID- 2911630 TI - Analysis of fibrogenic processes in denervated tissues of spinal cord injury patients. AB - To test the hypothesis that altered collagen metabolism is a contributing factor in the apparent delayed wound healing in denervated regions of spinal cord injury (SCI) patients, a tissue implant (PVA) was used to directly measure collagen deposition. Sterile PVA implants were placed subcutaneously in the inner aspect of the upper arm above the cord injury (innervated) and in the inner aspect of the upper leg below the cord injury (denervated) of 20 spinal cord injury patients and compared to eight healthy volunteers. On day 14, the implants were removed and analyzed histologically by trichrome stain and biochemically for hydroxyproline as a measure of collagen deposition. No remarkable histologic differences were observed in the sponge material removed from the upper regions compared to the lower denervated regions of the spinal cord injury patients. Sponges from both areas were infiltrated with fibroblasts containing well developed rough endoplasmic reticulum and large quantities of trichrome-positive collagen. Likewise, upper and lower histology of controls was identical and nondistinguishable from the corresponding sections obtained from the spinal cord injury patients. Quantitation of the hydroxyproline in the arms of the spinal cord injury patients (n = 20) showed 4.3 +/- 0.7 nmol hydroxyproline per milligram of sponge compared to 4.1 +/- 0.4 nmol/mg in the denervated regions of the lower limb. The hydroxyproline content in the arms of control volunteers was 5.2 +/- 0.7 nmol/mg compared to 3.9 +/- 0.8 nmol/mg in the leg (n = 8). These observations suggest that fibrogenic processes in denervated regions are not reduced significantly compared to innervated regions. PMID- 2911631 TI - The lack of effect of pentoxifylline on random skin flap survival. AB - The effects of pentoxifylline on skin flap survival were studied in rabbits. A total of 40 rabbits had caudally based single-pedicle flaps measuring 4 x 14 cm raised on the mid dorsum of each animal. Twenty of these rabbits were given intraperitoneal injections of pentoxifylline in doses of 24 mg/kg per day beginning 48 hours prior to flap construction and continued daily for 7 days postoperatively. The remaining 20 control rabbits received intraperitoneal injections of saline in equal volumes as the experimental groups. At the end of 7 days, viable flap length was visually inspected and measured in all 40 rabbits. There was no significant difference in skin flap viability in rabbits treated with pentoxifylline compared to the control group. PMID- 2911632 TI - Computer-aided analysis of Z-plasties. AB - Various Z-plasties were evaluated with a mathematical analytical method called the finite-element method. The lengthening and shortening effects on the skin proved to depend on the tip angle. Serial Z-plasties diminished the stress concentration after pairs of flaps had been transposed. Subdivided Z-plasties proved to be the most effective for lengthening. The finite-element method provided a good simulation of Z-plasties on a skin with complex properties. The lengthening and shortening effects on anisotropic skin were influenced not by the degree but by the direction of the anisotropy, whereas the total force required for transposing the two flaps was vice versa. The finite-element method was found to be useful for finding analytical solutions for biomechanical skin problems. PMID- 2911633 TI - Overobliging and underappreciated. PMID- 2911634 TI - Angioleiomyomas of the extremities: report of a case and review of the Mayo Clinic experience. AB - Angioleiomyomas are rare smooth-muscle tumors that occur anywhere in the body. We present the case of a 46-year-old woman with a 3-year history of a painless angioleiomyoma in the right-hand fourth web space with the typical histologic features of tortuous vascular channels and thick muscular walls. In the 39 cases of angioleiomyoma of an extremity treated at the Mayo Clinic, we found a male-to female ratio of 1:2.2, a mean age of 52 years, and pain as the presenting symptom in 67 percent of the patients. The lesions usually were less than 1 cm in diameter, and they decreased significantly in size with increasing patient age. Simple excision was curative. Angioleiomyoma should be considered in all patients with nodular lesions of an extremity. PMID- 2911635 TI - Malignant hyperthermia crisis. AB - Clearly the malignant hyperthermia crisis offers a significant challenge in the well cosmetic surgical patient. Aggressive early treatment is mandatory in these cases. Any delay can be disastrous. At times, the crisis may be aborted due to such therapy, leaving some doubt as to the current diagnosis. With such a disease entity, this is the hopeful scenario. PMID- 2911636 TI - One-stage reconstruction of a large upper lid defect in a newborn. AB - Full-thickness defects of the upper eyelids require immediate reconstruction to ensure protection of the cornea. A technique is described for a one-stage reconstruction of a large congenital defect of upper eyelid in a newborn. The reconstruction was composed of a mucosa-lined transpositional musculocutaneous flap. The advantages of this method over previous methods are discussed. PMID- 2911637 TI - Correction of the nasal tip deformity following repair of unilateral clefts of the upper lip. PMID- 2911638 TI - Bilobed flap in the release of postburn mentosternal contracture. AB - We have described in brief detail our experience with bilobed flaps in the release of postburn mentosternal synaechia. We have found this method handy, and it gives very good results. We reckon that this method has a prominent place in the release of this contracture, particularly in children who cannot provide adequate free-skin flaps for revascularization and in centers where the procedure is technically impossible. PMID- 2911639 TI - The modeling of skin expanders. AB - In this paper we present mathematical models of tissue expanders of several shapes. Within the restrictions of the models, relations are given between surface-area gain and volume of the expanders. It is shown that for the most frequently used expander shapes, the relevant formulas are simple and do not require computer facilities. It is discussed that the approach unavoidably leads to considerable overestimation of the area gain but may serve as a necessary starting point for further research. Furthermore, the rate of overestimation appears to follow such a regular pattern that it can quite easily be compensated for by means of a correcting factor. PMID- 2911641 TI - Continuing medical education. PMID- 2911640 TI - Charity, plastic surgery, and malpractice. PMID- 2911642 TI - Closing a difficult defect of the scalp. PMID- 2911643 TI - Medicine and charity, then and now. PMID- 2911644 TI - Involutional entropion revisited. PMID- 2911645 TI - The porcine gracilis musculocutaneous flap model. PMID- 2911646 TI - Skin punch biopsy in selected burn patients. PMID- 2911647 TI - The use of YAG-tipped contact laser in removing orbital lymphangiomas. PMID- 2911648 TI - Xomed nasal splints. PMID- 2911649 TI - Use of the expander for estimating required volume for breast reconstruction. PMID- 2911650 TI - Aneurysms and the sleeve technique for vessel anastomosis. PMID- 2911651 TI - Peer review for publication. PMID- 2911652 TI - Poor quality of clinical research in radiology: another indictment. PMID- 2911653 TI - Fine-needle aspiration of clinically occult breast lesions. PMID- 2911654 TI - MR imaging of treated mediastinal Hodgkin disease. PMID- 2911655 TI - Outpatient brachiocephalic angiography. PMID- 2911656 TI - Suspected recurrent rectosigmoid carcinoma after abdominoperineal resection: MR imaging and histopathologic findings. AB - Eleven patients who underwent abdominoperineal resection for rectosigmoid carcinoma were examined with magnetic resonance (MR) imaging for suspected recurrent tumor in the presacral space. There were 12 suspected masses in the 11 patients. Ten lesions were malignant, and in two lesions only nonneoplastic inflammatory tissue was found. The signal intensity (SI) of each lesion relative to that of muscle was determined visually and correlated with the histologic findings at surgery or biopsy. The SIs of malignant and benign lesions were indistinguishable. All lesions showed areas of high SI that correlated with carcinoma and tumor necrosis or with non-neoplastic inflammation and edema. Areas of low SI corresponded to reactive fibrous tissue (desmoplastic reaction) with small islands of tumor or to nonneoplastic fibrosis. MR imaging can be useful in determining the extent of suspected tumors, but SIs on T2-weighted images do not permit histologic diagnosis. In particular, distinction of benign from malignant tissue is difficult in tumors with a desmoplastic reaction. PMID- 2911657 TI - Acute myocardial ischemia and reperfusion: MR imaging with albumin-Gd-DTPA. AB - The utility of a macromolecular, intravascular contrast agent, albumin-gadolinium diethylenetriaminepentaacetic acid (DTPA), for the differentiation of acutely ischemic and reperfused myocardium on magnetic resonance (MR) images was investigated. Regional, reversible myocardial ischemia was produced in rats and confirmed. After reperfusion, flow to the compromised myocardial segment returned to baseline. Normal myocardium could not be differentiated from ischemic myocardium on nonenhanced MR images (n = 12). After 5 minutes of myocardial ischemia and after administration of albumin-Gd-DTPA, the ischemic zone involving the free wall of the left ventricle was characterized by the absence of significant enhancement. Normal myocardium appeared homogeneously enhanced (by 145%). This pattern persisted for up to 1 hour of myocardial ischemia. In six rats that underwent myocardial reperfusion after 5 minutes of ischemia, the normal and reperfused myocardium became isointense. Radiotracer studies with albumin-Gd-153-DTPA confirmed the decreased distribution of contrast agent to the ischemic myocardium, possibly due to decreased blood pool or a blocked primary delivery system in the ischemic myocardium. PMID- 2911658 TI - Gated cardiac MR imaging and P-31 MR spectroscopy in humans at 1.5 T. Work in progress. AB - The authors describe a technique to acquire gated cardiac proton magnetic resonance images and localized hydrogen-1 and phosphorus-31 spectra with a doubly tuned surface coil probe. The probe reduces study time because the need to exchange imaging and spectroscopy coils is eliminated, while at the same time the sensitivity of singly tuned coils is retained. In addition, the probe enhances the ability of the investigator to localize cardiac spectra spatially and temporally during the cardiac cycle. Spectra were acquired from the left ventricular myocardium in five volunteers, and systolic and diastolic gated P-31 spectra were shown. PMID- 2911659 TI - Intraoperative arteriography: comparison of conventional screen-film with photostimulable imaging plate radiographs. AB - This prospective study compared images obtained with a photostimulable imaging plate with matched images obtained with a conventional screen-film combination in 26 patients undergoing intraoperative arteriography. Diagnostic accuracy of the two techniques was assessed objectively, and image quality was assessed subjectively. In 16 patients (62%), the radiation exposure was reduced by 50% for the imaging plate technique by decreasing the mAs level generally used for the screen-film combination. Because of the dynamic range of the imaging plate system, no repeat examinations were necessary, while 12% of the screen-film studies had to be repeated because of over- or under-penetration. Imaging plate studies required 6% more time for processing than screen-film studies. Receiver operating-characteristic analysis indicated no difference in diagnostic accuracy between the two imaging techniques. Subjective evaluation also revealed no difference in observer preference for imaging plate or screen-film studies. The imaging plate technique is an excellent alternative to screen-film studies in the operating room. PMID- 2911660 TI - Interstitial lymphangiography: initial clinical experience with a dimeric nonionic contrast agent. AB - Interstitial lymphangiography performed with intradermal injection of a new nonionic dimeric contrast agent was used to examine 34 normal lower extremities and 35 lower extremities with proved lymphedema. An infusion pump was used to inject 2 mL of the contrast agent into the intradermal interdigital space at a rate of 0.1 mL/min. In all normal extremities, the injection deposit appeared homogeneous, and one to five lymph vessels could be identified. Diffusion of contrast agent into perilymphatic tissue occurred 30-40 cm proximal to the injection site; inguinal lymph nodes were, therefore, not routinely visualized. The findings at interstitial lymphangiography were abnormal in all extremities with advanced lymphedema. The results indicate that interstitial lymphangiography with the use of a nonionic dimeric contrast agent allows morphologic assessment of lymphatic vessels and facilitates the diagnosis of lymphatic obstructive disease. PMID- 2911661 TI - Ergotism as a consequence of thromboembolic prophylaxis. AB - Vasospasm related to ergot intoxication is unusual. The authors report the case of 15-year-old boy who developed vasospasm necessitating amputation, due to an ergot derivative prescribed for thromboembolic prophylaxis. The importance of prompt angiographic recognition and therapy is stressed. PMID- 2911662 TI - Quality assessment of randomized controlled trials of contrast media. AB - Numerous randomized controlled trials (RCTs) have been conducted to define the relative benefits of low-osmolality contrast media (LOM) and high-osmolality contrast media (HOM). Because of the clinical and economic significance of the conclusions drawn from these RCTs, the authors used a standardized instrument to evaluate the quality of study design and data analysis of 100 RCTs published between 1982 and 1987 that compared LOM and HOM. The mean quality score (+/- standard deviation) was 39 +/- 12 (maximum possible score, 100). The largest number of patients studied in any RCT was 435; the smallest was five. A majority of the RCTs received high scores on three attributes of quality, intermediate scores on seven, and low scores on nine. These results underscore the difficulty of designing, performing, analyzing, and reporting high-quality RCTs. Nevertheless, limitations in study design and data analysis need to be considered when interpreting results of these RCTs. Future RCTs comparing LOM and HOM should be performed with greater attention to basic elements of good study design and data analysis. PMID- 2911663 TI - Mortalities associated with use of a commercial suspension of polyvinyl alcohol. AB - Two cases of symptomatic neonatal hepatic arteriovenous malformation (AVM) are presented. Both were treated with percutaneous transcatheter embolization and a commercially available polyvinyl alcohol suspension. Both infants died soon after AVM embolization. The results of laboratory examination of particle-size homogeneity of this commercial suspension demonstrate marked inhomogeneity of particle size very probably contributed to the death of these patients. A protocol has been developed to help determine appropriate particle size in individual cases; this may help prevent such catastrophic results during transcatheter embolization. PMID- 2911664 TI - Breast hamartomas: variable mammographic appearance. AB - The mammograms of 17 women with pathologically proved breast hamartomas were reviewed. Abnormal masses were detected on 12. Nine women had masses with benign features. Two of these had findings considered classic for hamartoma. In three cases, the appearance of the mass was suggestive of carcinoma. The breasts were very dense in four of five women without detectable mass. The findings suggest that the classic mammographic appearance of breast hamartomas is less common than previously reported, which may be explained by earlier detection of small hamartomas. PMID- 2911665 TI - Residual mediastinal masses in Hodgkin disease: prediction of size with MR imaging. AB - Eighteen patients with mediastinal involvement of Hodgkin disease were examined with magnetic resonance (MR) imaging before and during therapy to find out if size of residual masses could be predicted from the MR characteristics of the tumor at diagnosis. After the first treatment, a significant decrease in T2 values and signal intensity ratios of tumor to fat and tumor to muscle was found in all patients. There was no significant change in T1 values. The relative decrease in tumor size correlated well with signal intensity ratios and poorly with T2 values of the original tumor. No correlation with T1 values was found. The authors conclude that size of the residual mass can be predicted from the initial size of the tumor and the signal intensity ratios at diagnosis. Since the degree of low signal intensity in the tumor before treatment probably reflects the amount of fibrotic tissue, these results support the hypothesis that residual masses after treatment are remnants of the fibrotic stroma of the original tumor. PMID- 2911666 TI - Laryngospasm-induced pulmonary edema. AB - Pulmonary edema after relief of airway obstruction due to laryngospasm is an uncommon but recognized entity. The authors report a case of a previously healthy young man who developed pulmonary edema after relief of laryngospasm following extubation of the trachea. Pulmonary edema after relief of acute airway obstruction should be included in the differential diagnosis of noncardiogenic pulmonary edema in the appropriate clinical setting. PMID- 2911667 TI - Complications of automatic implantable cardioverter defibrillators: radiographic, CT, and echocardiographic evaluation. AB - Automatic implantable cardioverter defibrillators (AICDs) were studied in three groups: (a) Serial radiographs were reviewed in 51 clinic patients. Twenty of 96 (21%) AICD patches distorted with time. (b) Thirty-six postoperative computed tomographic (CT) scans of asymptomatic patients revealed that pericardial fluid collections were frequent during the month after surgery but rare beyond that. Echocardiography was insensitive for these collections. CT also demonstrated dense fibrosis around some distorted patches, months after surgery. (c) Five other patients with pericardial infection had distorted patches, and the four studied with CT had fluid beneath their patches. (d) A case of constrictive pericarditis had distorted patches but was not diagnosed with CT. The authors conclude that distorted patches may indicate postoperative complications and that CT is the imaging modality of choice. PMID- 2911668 TI - Comparison of information-preserving and information-losing data-compression algorithms for CT images. AB - Data compression increases the number of images that can be stored on magnetic disks or tape and reduces the time required for transmission of images between stations. Two algorithms for data compression are compared in application to computed tomographic (CT) images. The first, an information-preserving algorithm combining differential and Huffman encoding, allows reconstruction of the original image. A second algorithm alters the image in a clinically acceptable manner. This second algorithm combines two processes: the suppression of data outside of the head or body and the combination of differential and Huffman encoding. Because the final image is not an exact copy, the second algorithm is information losing. Application of the information-preserving algorithm can double or triple the number of CT images that can be stored on hard disk or magnetic tape. This algorithm may also double or triple the speed with which images may be transmitted. The information-losing algorithm can increase storage or transmission speed by a factor of five. The computation time on this system is excessive, but dedicated hardware is available to allow efficient implementation. PMID- 2911669 TI - Reduction of T2* dephasing in gradient field-echo imaging. AB - Fast gradient field-echo imaging is becoming more common in morphologic studies but is not as widespread as might be hoped because of its susceptibility to local field inhomogeneities that lead to spin dephasing (reducing T2 to T2*) and geometric distortion (frequency misregistration). These problems are manifested in both the in-plane and section-select directions. The authors show that reversal of many of these adverse effects is possible through the acquisition of the gradient field echo in a three- and four-dimensional mode for a fixed echo time (TE), since phase-encoding leads to the capture of the echo within the sampling window. This echo centering is shown to be equivalent to the reduction of dephasing across a pixel. Improvements are also obtained by reducing TE to as short a value as possible. PMID- 2911670 TI - Anxiety in patients undergoing MR imaging. AB - To determine and quantify the major sources of anxiety for patients undergoing magnetic resonance (MR) imaging and to suggest means by which to eliminate or diminish their negative effects, the authors studied anxiety in 46 subjects. Of these, 20 randomly selected subjects who successfully completed the examination participated in exit interviews. Six subjects who terminated the examination before completion also completed exit interviews. Pre-imaging and postimaging questionnaires (state-trait anxiety inventory) were administered to measure anxiety in the 20 other subjects. Anxiety was associated with the constrictive dimensions of the magnet bore, examination duration, coil noise, and temperature within the bore. Preparation at the point of referral was consistently absent, incomplete, or misleading. Patients used identifiable strategies to cope with the examination: blinding, breathing relaxation techniques, visualization of pleasant images, and performance of mental exercises. PMID- 2911671 TI - Lymphangiomas in children: MR imaging. AB - Seventeen lymphangiomas in 15 patients were imaged with magnetic resonance (MR) to define the nature, extent, and anatomic relationships of these lesions. The MR and pathologic findings were then compared to determine the histologic basis for the signal-intensity characteristics of these lesions. The signal intensity of 13 lesions was similar to or slightly less than that of muscle on T1-weighted images and greater than that of fat on T2-weighted images. This appearance correlated with the presence of ectatic lymphatic channels containing clear fluid on histologic section. Four lymphangiomas had high signal intensity, approximately equal to that of fat, on T1-weighted images, reflecting the presence of clotted blood or small cystic spaces with a higher ratio of fat to fluid. Sixteen of 17 lesions had visible septations on MR images. The authors' experience suggests that most lymphangiomas have a characteristic appearance on MR images. The information obtained with MR imaging can help in providing a preoperative diagnosis, in planning surgical resection, and in defining recurrence. PMID- 2911672 TI - Ileocolic intussusception: new sign on the supine cross-table lateral radiograph. AB - The ability to detect ileocolic intussusception on the supine cross-table lateral radiograph of the abdomen in infants was prospectively evaluated in 12 cases (including two recurrences) over a 2-year period. The intussusceptions (including one recurrence) were directly depicted on five radiographs as a homogeneous water density mass producing a convex interface with bowel gas at the anterior part of the abdomen. In another four patients, the intussusception produced an inappropriate craniocaudal separation of gas-filled bowel loops in the upper part of the abdomen, caudal to the liver shadow. The intussusception was prospectively recognized on the supine cross-table lateral radiograph in nine of 12 cases. PMID- 2911673 TI - Isthmic spondylolysis of the lumbar spine: MR imaging at 1.5 T. AB - The appearance on magnetic resonance (MR) images of the normal pars interarticularis in 13 patients was reviewed and contrasted with that of the pars in eight patients with spondylolysis. The pars defect usually had an intermediate signal intensity with all pulse sequences; however, this intensity was somewhat variable depending on the exact ratio of cartilage, fat, and fluid within each bone defect. The pars defect was best seen with spin-echo 600/20 (repetition time msec/echo time msec) images. In three cases, out-of-phase images showed the spondylolysis best, because of extension of fat to the borders of the defect. The sagittal view allowed one to separate spondylolysis from the joint space of posterior facets since the orientation of the defects is perpendicular to the facets; thus, a common pitfall encountered with cross-sectional axial imaging techniques is avoided. MR imaging poorly delineated bone fragments around the defect, which may produce nerve root impingement, but revealed other numerous complications that occur with spondylolysis, including spondylolisthesis and herniation of the disk above. PMID- 2911674 TI - Structure, function, and degeneration of bovine hyaline cartilage: assessment with MR imaging in vitro. AB - The basic magnetic resonance (MR) imaging pattern of normal and degenerated hyaline articular cartilage was studied in vitro in 40 fresh bovine patellae. With the use of an ample spectrum of strongly T1- to T2-weighted sequences, two zones of cartilage with different signal intensities were observed in all specimens. A superficial cartilaginous layer in the MR image with higher water content and longer T1 and T2 correlated with the tangential and transitional zones of normal articular cartilage, whereas a second MR imaging zone with shorter T1 and T2 was identified in the depth of the articular cartilage. Different functional properties in pressure resistance were observed in the two layers. In early cartilage degeneration without thinning, there was increased hydration of the superficial cartilage layer. This study suggests that strongly T1- and T2-weighted images are indispensable for evaluating details in articular cartilage degeneration. PMID- 2911675 TI - Axial bone density in rheumatoid arthritis: comparison of dual-energy projection radiography and dual-photon absorptiometry. AB - The usefulness of dual-energy projection radiography (DEPR) in the evaluation of rheumatoid arthritis was compared with that of dual-photon absorptiometry (DPA). Bone density measurements of the lumbar spine and the proximal femur were obtained with DPA in 75 patients (45 women and 30 men). For comparison, the bone density of the lumbar spine was measured with DEPR in a subset of 52 patients (33 women and 19 men). High correlation was documented between DEPR and DPA measurements of the lumbar spine. No significant relationship between bone density and age was observed, in contrast to the known relationship in healthy subjects regardless of sex, site of measurement, or measurement technique. Bone density values in the spine and the proximal femur were significantly reduced for both sexes as compared with matched normative data. Interlevel variation in lumbar vertebral density as measured with DEPR was not significantly different in patients with rheumatoid arthritis as compared with control subjects. Significant correlation between bone density determination and body weight, as well as duration of menopause, was noted, whereas duration of disease, functional status, and cumulative corticosteroid dose were not predictive. Rheumatoid arthritis did not appear to influence the relationship between DEPR and DPA measurements of the spine, and neither method nor site of measurement exhibited a consistent advantage in discriminating patients with rheumatoid arthritis from healthy control subjects. PMID- 2911676 TI - Depth insufficiency of the proximal trochlear groove on lateral radiographs of the knee: relation to patellar dislocation. AB - The depth of the trochlear groove was frequently noted to be insufficient in knees with patellar instability, particularly in the proximal portion of the trochlea. To confirm this observation, the depth of the trochlear groove of the femur was measured on lateral radiographs of 218 knees: 40 knees in 20 asymptomatic subjects, 116 knees in 69 patients undergoing radiography for various symptoms (96 without and 20 with patellar subluxation, determined on axial radiographs), and 62 knees in 34 patients who underwent surgery for recurrent dislocation or subluxation of one or both patellae (40 treated and 22 contralateral knees). In the 40 knees that had been operated on, the proximal trochlear depth (measured 1 cm below the upper limit of the trochlear groove) was 2.74 mm +/- 1.35, in contrast to 5.94 mm +/- 1.74 in the asymptomatic subjects and 5.84 mm +/- 1.53 in the patients with symptoms but no patellar instability. Recognition of depth insufficiency in the proximal portion of the trochlea should prompt a search for patellar instability. Axial views made with 30 degrees of knee flexion and lateral rotation of the leg are particularly helpful. PMID- 2911677 TI - Frostbite injury: prediction of tissue viability with triple-phase bone scanning. AB - Triple-phase bone scans were obtained in seven patients within 48 hours of admission for frostbite injuries. Three patterns of perfusion imaging and delayed bone imaging were observed: hyperemic blood flow with normal early blood pool and normal delayed bone images; absent blood flow and absent early blood pool depiction, but depiction of bone in delayed images; and absent perfusion and absent blood pool depiction, with no bone uptake in the delayed images. The first pattern indicated mild ischemia that required no surgical treatment, the second indicated ischemia with occasional superficial tissue infarction that required minor debridement, and the third pattern indicated deep-tissue and bone infarction that required amputation. The triple-phase bone scan is a useful indicator of tissue viability as early as 2 days after cold injury and appears to have a clinical role in the evaluation of frostbite injuries. The perfusion and blood pool images demonstrate the ischemic tissue at risk, while the delayed bone scan images demonstrate the extent of deep-tissue and bone infarction. PMID- 2911678 TI - Body fat distribution measured with CT: correlations in healthy subjects, patients with anorexia nervosa, and patients with Cushing syndrome. AB - Computed tomography (CT) was used to study fat distribution in three groups of women of comparable age: 39 healthy volunteers, 15 patients with anorexia nervosa, and seven with Cushing syndrome. Patients with anorexia nervosa had a fivefold decrease in subcutaneous fat and only a twofold decrease in intraabdominal fat compared with the values for the volunteers. Patients with Cushing syndrome had less than a twofold increase in subcutaneous fat and greater than a fivefold increase in intraabdominal fat compared with values for the healthy subjects. These findings suggest that fat in different body compartments responds differently to disease processes and that CT can be used to measure these changes. PMID- 2911679 TI - Head and neck lesions: MR-guided aspiration biopsy. AB - Aspiration biopsy guided with computed tomography (CT) has long been a valuable tool in the evaluation of head and neck disease. The ability to obtain diagnoses without the need for surgery has had a significant effect on patient treatment. Magnetic resonance (MR) imaging is now rapidly replacing CT as the primary imaging study for many head and neck diseases. The standard stainless steel needles used for CT-guided biopsy are unsuitable for MR-guided biopsy because significant ferromagnetic artifacts obscure the underlying anatomy. A new needle has recently been designed specifically for use with MR imaging. This needle has far less magnetic susceptibility and therefore does not cause significant image distortion. The authors describe the use of this needle in MR-guided aspiration biopsy of a variety of lesions in the head and neck. PMID- 2911680 TI - Criteria for classifying normal and degenerated lumbar intervertebral disks. AB - The purpose of this study was to develop criteria for distinguishing normal and degenerated lumbar intervertebral disks. Cryomicrotome sections from and magnetic resonance images of 31 cadavers were reviewed. The immature nucleus pulposus, found up to age 2 years; the transitional nucleus pulposus, found in teenagers; and the adult nucleus pulposus were associated with an intact anulus fibrosus without tears except for small concentric or transverse tears in the periphery of the anulus fibrosus. Discoloration of the nucleus pulposus, diminishing disk height, and diminishing signal intensity were associated consistently with a radial tear of the anulus fibrosus. The severely degenerated nucleus pulposus was associated also with a radial tear or complete disruption of the anulus fibrosus. The results suggest that intervertebral disk normally progresses from the immature to the transitional to the adult nucleus pulposus. When a radial tear develops in the anulus there is shrinkage and disorganization of fibrocartilage in the nucleus pulposus and replacement of the disk by dense fibrous tissue and cystic spaces. PMID- 2911681 TI - Intraspinal synovial cysts: MR imaging. AB - Juxtaarticular intraspinal synovial cysts are unusual lesions of the spine associated with facet arthropathy. These lesions can cause radicular symptoms and may masquerade clinically as other, more common entities. Synovial cysts have been detected at myelography and have been well characterized at computed tomography as posterolateral epidural masses, typically at L4-5. Six synovial cysts of the lumbar spine were demonstrated on magnetic resonance (MR) images. The signal-intensity patterns of these lesions are variable. MR imaging can be used to document the presence of hemorrhage within the cyst, which may relate to the exacerbation of symptoms. Air-filled synovial cysts may be difficult to detect and distinguish from facet arthropathy. PMID- 2911682 TI - Recurrent postoperative sciatica: evaluation with MR imaging and enhanced CT. AB - Magnetic resonance (MR) imaging and computed tomography enhanced with intravenous iodine injection (ECT) were prospectively compared in 80 patients in the diagnosis of recurrent postoperative sciatica. Diagnostic accuracy was determined with surgical verification. Isolated fibrosis was considered a contraindication to surgery. A decision to operate was made in 56 of the 80 patients on the basis of MR imaging findings; in 21 of the 56, the decision was also made on the basis of ECT findings. Of the 80 patients, 45 underwent surgery, In all but one of these patients, the diagnosis made on the basis of MR imaging findings was confirmed with surgical analysis. The only surgical finding that did not agree with MR imaging findings was a calcification of the common posterior ligament. The 21 diagnoses of disk herniation based on ECT findings were confirmed surgically, but among the 24 diagnoses of fibrosis made with the help of ECT, there were actually 19 recurrent herniations, four herniations with fibrosis, and one herniation at the level above the previously resected disk. MR imaging seems to be the investigation of choice in diagnosing the cause of recurrent postoperative sciatica. PMID- 2911683 TI - Pelvic actinomycosis associated with intrauterine devices. AB - The authors describe two women with pelvic pain, long-term use of an intrauterine device, and a pelvic mass due to Actinomyces israelii. The diagnostic imaging findings were nonspecific but included mass effect and mucosal irregularity of the rectosigmoid colon at barium enema examination and complex masses and inflammatory changes at computed tomography and magnetic resonance imaging. Radiologists should be aware of the imaging findings of this potentially lethal but curable condition. PMID- 2911684 TI - Catheter for endoluminal bipolar electrocoagulation. AB - An interventional catheter was designed that can induce controlled endoluminal tissue lesions by means of bipolar radio-frequency (RF) electrocoagulation under fluoroscopic guidance. The technique was used to obtain safe and reproducible percutaneous occlusion of the porcine cystic duct by reactive endoluminal scar formation. The new triple-lumen, 7-F, polyethylene catheter contains two insulated active wires and accommodates a 0.038-inch steerable guide wire, which facilitates insertion and placement of the active catheter tip under fluoroscopic control. The coagulation technique is relatively simple and requires only a small, portable bipolar RF generator and ammeter. PMID- 2911685 TI - Hepatic transcatheter arterial embolization with gastroduodenal artery blocking by finger compression. AB - Hepatic transcatheter arterial embolization was performed in two patients by blocking the gastroduodenal artery with finger compression on the abdominal surface. The embolizing material, which was injected into the common hepatic artery, did not enter the gastroduodenal artery. No postoperative complications were experienced. This method may be useful for patients in whom superselective catheterization of the proper hepatic artery is not feasible. PMID- 2911686 TI - Manual compression device for fluoroscopy. AB - A device for manual compression and palpation during supine fluoroscopy has been designed. It enables effective use of the physiologic grasping and lever force potentials of the hand and wrist. The device permits optimal fluoroscopic palpation and compression techniques and prevents direct exposure to the lead gloved hand. PMID- 2911687 TI - Patellofemoral joint: 30 degrees axial radiograph with lateral rotation of the leg. AB - A method for axial radiography of the patellofemoral joint has been developed that combines a forced lateral rotation of the leg with 30 degrees flexion of the knee. This view can be obtained without any special device and is definitely superior to the 45 degrees routine axial view in the detection of lateral subluxation of the patella. It should be obtained when patellar instability is suspected. PMID- 2911688 TI - The procrustean bed and the self-anointed raters. AB - Taking the lead from a published rating of radiology/nuclear medicine journals in which, surprisingly, Radiology ranks number 3, the author critically analyzes the formalized statistics-based assessment of the diagnostic radiologic activities. The specific ranking in question is shown to result from an inconsistent treatment of the primary data. Generalizing the discussion, he argues that the radiodiagnostic process, based on image evaluation, is not a suitable candidate for rigidly codified statistical appraisal. Attempts at obtaining by such methods meaningful and timely information on the respective values of rapidly changing radiodiagnostic techniques are not likely to succeed. PMID- 2911689 TI - Can the newer interventional procedures replace cholecystectomy for cholecystolithiasis? PMID- 2911690 TI - Decreased breast cancer mortality through mammographic screening. PMID- 2911691 TI - Clinical history, radiographic reporting, and defensive radiologic practice. PMID- 2911692 TI - Impact of clinical history on fracture detection with radiography. PMID- 2911693 TI - Is reform needed in the book review process? PMID- 2911694 TI - Excellent anxiolytic effect achieved with low doses of Versed. PMID- 2911695 TI - A nurse-managed multiple sclerosis clinic: improved quality of life for persons with MS. AB - Multiple sclerosis (MS) is a complex disease, the symptoms of which may wax and wane on a daily basis. Conventional treatment for MS patients may involve numerous trips to a variety of clinics, physicians, and rehabilitation settings. This article describes a nurse-managed MS clinic which employs an interdisciplinary and holistic approach to treatment of MS patients with the goal of improving their quality of life and coordinating their health care. In this article, the services of the clinic are described, emphasizing the roles of the nurse practitioner (clinic manager), rehabilitation nurse specialist, and nursing director of the hospital-based home care program. A case study example of the interdisciplinary nature of this clinic's program with one MS patient is included. PMID- 2911696 TI - Falls in the rehabilitation setting: incidence and characteristics. AB - A prospective six-month study was conducted to determine a high-risk index for medical rehabilitation patients who fall. Variables studied for all patients included demographics, medical conditions, associated symptoms, orthostatic blood pressure measurements, physical function, posture control, proprioception, use of physical restraints, and medications, A detailed examination of the fall events was also conducted. Of the 143 patients studied, 46 (32%) fell at least once, making a total of 84 falls. Impaired ability to follow directions, impaired judgment, impaired proprioception, presence of physical restraints, use of major tranquilizers, use of sedatives, and presence of psychiatric diagnosis were all individually associated with patients who fell. Males fell more than females. Logistic regression identified altered proprioception as the only major predictor of falling. Of those who fell, only 26% called for assistance prior to the fall. Sixty-eight percent of the falls were from wheelchairs. Importantly, no patients had serious injury or morbidity from the falls. PMID- 2911697 TI - Hyponatremia in spinal cord injured persons. PMID- 2911698 TI - A personal view of independent living. PMID- 2911699 TI - Determinants of well-being in primary caregivers of spinal cord injured persons. AB - A study of well-being in middle-aged and elderly spinal cord injured persons (Decker & Schulz, 1985) found that long-term coping was facilitated by the presence of a primary support person or caregiver. The purpose of this study was to identify the determinants of life satisfaction and depression in 67 primary caregivers of middle-aged and elderly spinal cord injured persons. The study revealed that the availability of social support and feelings of control over one's life were important determinants of caregivers' well-being. In addition, those caregivers spending more time each day assisting the disabled person and feeling burdened by these responsibilities experienced more depression and less life satisfaction. In working with spinal cord injured persons, rehabilitation nurses must consider the well-being of the spinal cord injured person/primary caregiver dyad as an important focus of nursing assessment and intervention. PMID- 2911700 TI - Relationship between self-concept and successful rehabilitation. AB - One hundred fifty-seven spinal cord injured (SCI) individuals from three SCI centers were tested to investigate the relationship between self-concept and adjustment to rehabilitation. It was hypothesized that strong positive correlations would be found that neither time since injury nor level of injury would be a factor. The Tennessee Self-Concept Scale (TSCS) provided a measure of self-concept. Criteria for differentiating adjustment into a six-point scale was used by nurses to assess rehabilitation success. Thirteen subsets of the TSCS correlated significantly with the nurses assessment. A norm deviate score from the TSCS showed P less than .001. Variables of sex, inpatient/outpatient and time since injury were not significant; however, level of injury was slightly significant. PMID- 2911701 TI - I can't be calm about nursing's image. PMID- 2911702 TI - Taking charge. How to get people to follow your lead. PMID- 2911703 TI - Patient's advocate. When divorce complicates care. PMID- 2911704 TI - The anemias: causes and courses of action (continuing education credit). PMID- 2911705 TI - How to take nursing skills on the road. PMID- 2911706 TI - Zidovudine: flawed champion against AIDS. PMID- 2911707 TI - Are your i.v. chemo skills up-to-date? PMID- 2911708 TI - Managing an implanted infusion device. PMID- 2911709 TI - When the bile duct is blocked. PMID- 2911710 TI - The new risks of home care. PMID- 2911711 TI - Detecting the hidden UTI. PMID- 2911712 TI - Petition on Dugway facility. PMID- 2911713 TI - FDA approval of HTLV-I tests. PMID- 2911714 TI - Universities fight animal activists. PMID- 2911715 TI - NIH scientists agonize over technology transfer. PMID- 2911716 TI - NSF opens high-speed computer network. PMID- 2911717 TI - Is it chaos, or is it just noise? PMID- 2911718 TI - Neurotoxicity creates regulatory dilemma. PMID- 2911719 TI - Protein structure determination in solution by nuclear magnetic resonance spectroscopy. AB - Knowledge of three-dimensional protein structures is one of the foundations of protein design and protein engineering. Nuclear magnetic resonance spectroscopy was recently introduced as a second method for protein structure determination, in addition to the well-established diffraction techniques with protein single crystals. This new approach enables one to carry out detailed structural studies of proteins in solution and other noncrystalline states, which may be similar or identical to the physiological environment, and promises new insights into the dynamics of protein molecules and the protein-folding problem. PMID- 2911720 TI - Phylogenetic meaning of the kingdom concept: an unusual ribosomal RNA from Giardia lamblia. AB - An analysis of the small subunit ribosomal RNA (16S-like rRNA) from the protozoan Giardia lamblia provided a new perspective on the evolution of nucleated cells. Evolutionary distances estimated from sequence comparisons between the 16S-like rRNAs of Giardia lamblia and other eukaryotes exceed similar estimates of evolutionary diversity between archaebacteria and eubacteria and challenge the phylogenetic significance of multiple eukaryotic kingdoms. The Giardia lamblia 16S-like rRNA has retained many of the features that may have been present in the common ancestor of eukaryotes and prokaryotes. PMID- 2911721 TI - Pavlovian conditioning of rat mucosal mast cells to secrete rat mast cell protease II. AB - Antigen (egg albumin) injections, which stimulate mucosal mast cells to secrete mediators, were paired with an audiovisual cue. After reexposure to the audiovisual cue, a mediator (rat mast cell protease II) was measured with a sensitive and specific assay. Animals reexposed to only the audiovisual cue released a quantity of protease not significantly different from animals reexposed to both the cue and the antigen; these groups released significantly more protease than animals that had received the cue and antigen in a noncontingent manner. The results support a role for the central nervous system as a functional effector of mast cell function in the allergic state. PMID- 2911722 TI - Structural origins of high-affinity biotin binding to streptavidin. AB - The high affinity of the noncovalent interaction between biotin and streptavidin forms the basis for many diagnostic assays that require the formation of an irreversible and specific linkage between biological macromolecules. Comparison of the refined crystal structures of apo and a streptavidin:biotin complex shows that the high affinity results from several factors. These factors include the formation of multiple hydrogen bonds and van der Waals interactions between biotin and the protein, together with the ordering of surface polypeptide loops that bury the biotin in the protein interior. Structural alterations at the biotin binding site produce quaternary changes in the streptavidin tetramer. These changes apparently propagate through cooperative deformations in the twisted beta sheets that link tetramer subunits. PMID- 2911723 TI - Gating of retinal transmission by afferent eye position and movement signals. AB - Vision in most vertebrates is an active process that requires the brain to combine retinal signals with information about eye movement. Eye movement information may feed forward from the motor control areas of the brain or feed back from the extrinsic eye muscles. Feedback signals elicited by passive eye movement selectively gate retinal outflow at the first relay, the dorsal lateral geniculate nucleus. The gating predominantly facilitates retinogeniculate transmission immediately after eye movement and inhibits transmission when a new steady-state eye position is achieved. These two gating effects are distributed in a complementary fashion across the dorsal lateral geniculate nucleus such that the spatiotemporal activity profile could contribute to object detection and localization. PMID- 2911724 TI - Progress at AAAS. PMID- 2911725 TI - The holly oak shell. PMID- 2911726 TI - Orangutan tool use. PMID- 2911727 TI - Science and the lame-duck budget. PMID- 2911728 TI - Europe bans boeuf a l'estradiol. PMID- 2911730 TI - Genome project under way, at last. PMID- 2911729 TI - Leadership and AIDS. PMID- 2911731 TI - "Fragile X" syndrome and its puzzling genetics. PMID- 2911733 TI - Observation of individual DNA molecules undergoing gel electrophoresis. AB - Individual DNA molecules undergoing agarose gel electrophoresis were viewed with the aid of a fluorescence microscope. Molecular shape and orientation were studied in both steady and pulsed electric fields. It was observed that (i) DNA macromolecules advanced lengthwise through the gel in an extended configuration, (ii) the molecules alternately contracted and lengthened as they moved, (iii) the molecules often became hooked around obstacles in a U-shape for extended periods, and (iv) the molecules displayed elasticity as they extended from both ends at once. A computer model has been developed that simulates the migration of the molecules in a rotating-field gel electrophoresis experiment. PMID- 2911732 TI - Molecular sorting in the secretory pathway. AB - Proteins can be secreted from animal cells by either a constitutive or a regulated pathway; those destined for regulated secretion are actively sorted into dense-core secretory granules. Although sorting is generally assumed to be accomplished by specific carriers, the nature of these carriers remains elusive. In this study, peptide hormones were used as affinity ligands to purify a set of 25-kilodalton proteins from canine pancreatic tissue. Their ligand specificities and patterns of expression have the characteristics of sorting carriers. PMID- 2911734 TI - A new cluster of genes within the human major histocompatibility complex. AB - A 435-kilobase (kb) DNA segment, which is centromeric to HLA-B in the human major histocompatibility complex, was isolated by chromosome walking with overlapping cosmids. Within the cloned region, the genes for the tumor necrosis factors (TNFs) alpha and beta and HLA-B were 210 kb apart. The human homolog of a mouse gene, B144, was located next to TNF alpha. Moreover, the presence of additional genes was suggested by a large cluster of CpG islands. With cosmid probes, several distinct transcripts were detected in RNA samples from a variety of cell lines. Altogether, five novel genes were identified by isolation of corresponding complementary DNA clones. These "HLA-B-associated transcripts" (BATs) were mapped to different locations within a 160-kb region that includes the genes for TNF alpha and TNF beta. The presence of the genes for BAT1 and BAT5 in the vicinity of HLA-B again raises the question of which gene in this region determines susceptibility to ankylosing spondylitis. PMID- 2911735 TI - High-level recombinant gene expression in rabbit endothelial cells transduced by retroviral vectors. AB - By virtue of its immediate contact with the circulating blood, the endothelium provides an attractive target for retroviral vector transduction for the purpose of gene therapy. To see whether efficient gene transfer and expression was feasible, rabbit aortic endothelial cells were infected with three Moloney murine leukemia virus-derived retroviral vectors. Two of these vectors carry genes encoding products that are not secreted: N2, containing only the selectable marker gene neoR, and SAX, containing both neoR gene and an SV40-promoted adenosine deaminase (ADA) gene. The third vector, G2N, contains a secretory rat growth hormone (rGH) gene and an SV40-promoted neoR gene. Infection with all three vectors resulted in expression of the respective genes. A high level of human ADA expression was observed in infected endothelial cell populations both before and after selection in G418. G2N-infected rabbit aortic endothelial cells that were grown on a synthetic vascular graft continued to secrete rGH into the culture medium. These studies suggest that endothelial cells may serve as vehicles for the introduction in vivo of functioning recombinant genes. PMID- 2911736 TI - Dynamic expression pattern of the myc protooncogene in midgestation mouse embryos. AB - The c-myc protooncogene in mouse embryos was shown by RNA in situ hybridization to be preferentially expressed in tissues of endodermal and mesodermal origin. Most organs developing from the ectoderm, such as skin, brain, and spinal cord, displayed low levels of c-myc RNA. The thymus represented the only hematopoietic organ with high c-myc expression. In organs and structures strongly hybridizing to c-myc probes, for example the fetal part of the placenta, gut, liver, kidney, pancreas, submandibular glands, enamel organs of the molars, and skeletal cartilage, the level of expression depended on the stage of development. Expression was observed to be correlated with proliferation, particularly during expansion and folding of partially differentiated epithelial cells. PMID- 2911737 TI - Mental rotation of the neuronal population vector. AB - A rhesus monkey was trained to move its arm in a direction that was perpendicular to and counterclockwise from the direction of a target light that changed in position from trial to trial. Solution of this problem was hypothesized to involve the creation and mental rotation of an imagined movement vector from the direction of the light to the direction of the movement. This hypothesis was tested directly by recording the activity of cells in the motor cortex during performance of the task and computing the neuronal population vector in successive time intervals during the reaction time. The population vector rotated gradually counterclockwise from the direction of the light to the direction of the movement at an average rate of 732 degrees per second. These results provide direct, neural evidence for the mental rotation hypothesis and indicate that the neuronal population vector is a useful tool for "reading out" and identifying cognitive operations of neuronal ensembles. PMID- 2911738 TI - Predation on ocean krill. PMID- 2911739 TI - Habitat compartmentation and environmental correlates of food chain length. PMID- 2911740 TI - Cornell cat study. PMID- 2911741 TI - Asking America about its sex life. PMID- 2911742 TI - A corrosive fight over California's toxics law. PMID- 2911743 TI - Troubles encountered in gene linkage land. PMID- 2911744 TI - Prevalence and patterns of same-gender sexual contact among men. AB - The prevalence and patterns of same-gender sexual contact among men are key components of models of the spread of HIV infection and AIDS in the U.S. population. Previous estimates by Kinsey et al. from data collected between 1938 and 1948 have been widely criticized for inadequacies of sample design. New lower bound estimates of prevalence developed from data from a national sample survey conducted in 1970 indicate that minimums of 20.3 percent of adult men in the United States in 1970 had sexual contact to orgasm with another man at some time in life; 6.7 percent had such contact after age 19; and between 1.6 and 2.0 percent had such contact within the previous year. Although these estimates incorporate adjustments for missing data, the likelihood of underreporting suggests that these estimates might be lower bounds on the prevalence of same gender sex among men. Two sets of alternative estimates are derived to assess the sensitivity of these estimates to the assumptions made in imputing values to missing data. Detailed estimates are presented by frequency of contact, age, education, and marital status; and supporting estimates are derived from a 1988 national survey. Data from both the 1970 and 1988 surveys indicate that never married men are more likely than other men to have had same-gender sexual contacts within the last year. The 1970 survey also indicates, however, that approximately half the men estimated to have such contacts are found among the more numerous population of currently or previously married men. PMID- 2911745 TI - Pheromone-mediation of host-selection in bont ticks (Amblyomma hebraeum koch). AB - The bont tick, Amblyomma hebraeum, is the principal vector to southern African ruminants of heartwater (Cowdria ruminantium infection). The role of feeding male ticks, which emit an aggregation-attachment pheromone, in attracting unfed ticks to cattle was investigated. Calves infested with feeding male ticks were more attractive to unfed adult ticks than were uninfested calves. The presence of the pheromone on previously infested cattle apparently allows unfed ticks to discriminate between hosts on which these parasites have fed successfully (suitable hosts) and those on which they have not (potentially unsuitable hosts). The use of acaricides is thus unlikely to reduce bont tick populations in areas where adequate numbers of alternate (wild) hosts are present. Also, cattle so treated may lose their resistance to heartwater through lessened exposure to infected ticks. PMID- 2911746 TI - The perception of intention. AB - Classical work on the perception of causality in humans is extended to the perception of intention. Two experiments explored the sensitivity of preschool children to intentional events that can be stated in terms of time and distance only. In habituation-dishabituation of attention tests, preschool children differentiated between intentional movement patterns of two balls and the nonintentional control events where the movements were desynchronized. Also, reversal of the roles of the balls produced more recovery of attention in the intentional case than it did in the nonintentional case. PMID- 2911747 TI - Direct observation of native DNA structures with the scanning tunneling microscope. AB - Uncoated double-stranded DNA dissolved in a salt solution was deposited on graphite and imaged in air with the scanning tunneling microscope (STM). The resolution was such that the major and minor grooves could be distinguished. The pitch of the helix varied between 27 and 63 angstroms in the images obtained. Thus the STM can be useful for structural studies of a variety of uncoated and isolated biomolecules. PMID- 2911748 TI - Increased expression of DNA cointroduced with nuclear protein in adult rat liver. AB - DNA and nuclear proteins were transferred into cells simultaneously at more than 95% efficiency by means of vesicle complexes. The DNA was rapidly transported into the nuclei of cultured cells, and its expression reached a maximum within 6 to 8 hours after its introduction. Moreover, when the plasmid DNA and nuclear protein were cointroduced into nondividing cells in rat liver by injection into the portal veins of adult rats, the plasmid DNA was carried into liver cell nuclei efficiently by nuclear protein. The expression of the DNA in adult rat liver, on introduction of the DNA with nuclear protein, was more than five times as great as with nonnuclear protein. PMID- 2911749 TI - Isolation and expression of functional high-affinity Fc receptor complementary DNAs. AB - Human and murine mononuclear phagocytes express a high-affinity receptor for immunoglobulin G that plays a central role in macrophage antibody-dependent cellular cytotoxicity and clearance of immune complexes. The receptor (FcRI) may also be involved in CD4-independent infection of human macrophages by human immunodeficiency virus. This report describes the isolation of cDNA clones encoding the human FcRI by a ligand-mediated selection technique. Expression of the cDNAs in COS cells gave rise to immunoglobulin G binding of the expected affinity and subtype specificity. RNA blot analysis revealed expression of a 1.7 kilobase transcript in macrophages and in cells of the promonocytic cell line U937 induced with interferon-gamma. The extracellular region of FcRI consists of three immunoglobulin-like domains, two of which share homology with low-affinity receptor domains. PMID- 2911750 TI - The involvement of platelet activating factor in ovulation. AB - Follicle rupture during ovulation is associated with inflammation-like changes. Because platelet activating factor (PAF) participates in the inflammatory process, the effect of a PAF-specific antagonist, BN52021, on the ovulatory response was tested in rats. BN52021, administered locally, inhibited follicle rupture in rats stimulated to ovulate with human chorionic gonadotropin (hCG). In addition to suppressing rupture of the follicles, this antagonist suppressed the hCG-stimulated increase in ovarian collagenolysis and vascular permeability. The inhibition of ovulation of BN52021 could be reversed by simultaneous administration of PAF. Furthermore, PAF partially reversed the blockage of ovulation by inhibitors of eicosanoid synthesis. Collectively, these results suggest the involvement of PAF in ovulation. Its role seems to be closely related to the metabolism of arachidonic acid. Thus, modulation of PAF action may serve as an additional target for regulation of reproduction via its action on ovulation. PMID- 2911752 TI - Evolution and family homicide. PMID- 2911751 TI - Plasticity and differentiation of embryonic retinal cells after terminal mitosis. AB - The relation between terminal mitosis and the events that determine the developmental fate of embryonic precursor cells is not well understood. This relation has now been investigated with [3H]thymidine autoradiography to determine the time of cell birth and with a culture system that allows the testing of the developmental potential of cells isolated from the chick embryo retina. Contrary to the situation in vivo, where neuronal differentiation always precedes photoreceptor differentiation, photoreceptor differentiation occurs prematurely and precedes neuronal differentiation when precursor cells are isolated from the retina at early embryonic stages. Thus, cells born by embryonic day 5 (ED-5) give rise predominantly to photoreceptors when isolated for culture on ED-6 but develop mainly as neurons when isolated on ED-8. This suggests that retinal precursor cells retain after terminal mitosis the capacity to develop either as neurons or as photoreceptors. Moreover, photoreceptor differentiation appears to represent a constitutive or "default" pathway that precursor cells follow in the absence of neuron-inducing signals. PMID- 2911753 TI - Human gene transfer test approved. PMID- 2911754 TI - Are neural nets like the human brain? PMID- 2911755 TI - Inbreeding costs swamp benefits. PMID- 2911756 TI - Selective loss of hippocampal granule cells in the mature rat brain after adrenalectomy. AB - Adrenalectomy of adult male rats resulted in a nearly complete loss of hippocampal granule cells 3 to 4 months after surgery. Nissl and immunocytochemical staining of hippocampal neurons revealed that the granule cell loss was selective; there was no apparent loss of hippocampal pyramidal cells or of gamma-amino butyric acid (GABA)-, somatostatin-, neuropeptide Y-, calcium binding protein-, or parvalbumin-containing hippocampal interneurons. The hippocampal CA1 pyramidal cells of adrenalectomized animals exhibited normal electrophysiological responses to afferent stimulation, whereas responses evoked in the dentate gyrus were severely attenuated. Corticosterone replacement prevented both the adrenalectomy-induced granule cell loss and the attenuated physiological response. Thus, the adrenal glands play a role in maintaining the structural integrity of the normal adult brain. PMID- 2911757 TI - Evidence that the leucine zipper is a coiled coil. AB - Recently, a hypothetical structure called a leucine zipper was proposed that defines a new class of DNA binding proteins. The common feature of these proteins is a region spanning approximately 30 amino acids that contains a periodic repeat of leucines every seven residues. A peptide corresponding to the leucine zipper region of the yeast transcriptional activator GCN4 was synthesized and characterized. This peptide associates in the micromolar concentration range to form a very stable dimer of alpha helices with a parallel orientation. Although some features of the leucine zipper model are supported by our experimental data, the peptide has the characteristics of a coiled coil. PMID- 2911758 TI - Emergency cardiac maneuvers. PMID- 2911759 TI - Economics of trauma in a small academic medical center. AB - The recent changes in the mechanisms of health care funding have complicated trauma care and trauma center development. Hard data are needed on the current financial position of trauma care to plan for the future. To reduce the cost of trauma care without sacrificing the quality, we must know how the trauma dollar is spent. We reviewed the records of 100 random admissions to the trauma service of our institution in 1985. The records were examined for length of stay (LOS), intensive care unit length of stay (ICU-LOS), total hospital bill, types of third party coverage, and overall collection rate. The hospital bill was broken down to identify the origins of trauma costs. To provide a control group, 100 patients admitted to the general surgical service and 100 other admissions were also analyzed. Trauma patients had greater LOS, ICU-LOS, total bills, and costs per day. Blunt trauma resulted in a greater LOS than penetrating trauma, but similar total bills. The collection rate from the blunt trauma patients was significantly greater. The greatest differences between trauma patients and others in resource utilization are the result of longer ICU-LOS and greater use of blood products. We did not identify any sites of potentially significant cost cutting that would not compromise patient care. PMID- 2911760 TI - Clostridial bloodstream infections. AB - In a ten-year review at a large community teaching hospital clostridia accounted for less than 1% of all positive bloodstream isolates (26 episodes in 25 patients). All but one of the isolates were clinically significant. Twenty-two patients (88%) had a serious underlying medical condition, and 17 of the episodes (65%) were associated with a bowel source; twelve patients (48%) died of their infection. Clostridial bloodstream infections are particularly clinically significant in patients with serious underlying disease. PMID- 2911761 TI - Elderly patients' satisfaction with care under HMO versus private systems. AB - In one community, 100 elderly persons (25 HMO and 75 private patients) completed a 20-item scale that measured satisfaction with medical care. Data on demographics, health care utilization, and self-assessed health status also were collected to determine whether these variables would relate to HMO membership. Satisfaction scores were compared between HMO and private care groups by multivariate analysis of variance. Satisfaction with the doctor-patient relationship and convenience of care was higher in the private care group, whereas satisfaction with cost was higher in the HMO group. Interestingly, the HMO group evaluated private care and HMO care similarly. The private group rated HMO care less favorably. Additional comments reveal specific areas of satisfaction/dissatisfaction. PMID- 2911762 TI - Fever and abdominal pain in a southeast Asian man. AB - Oriental cholangitis is a common illness among immigrants from Southeast Asia. It is distinct from typical western cholangitis, and it is easily misdiagnosed unless a high index of suspicion is maintained. After stabilization with appropriate antimicrobial therapy, surgical drainage of the biliary tree is often advocated. PMID- 2911763 TI - Humor and the physician. PMID- 2911764 TI - Teaching the informed consent process to residents. AB - We believe the focus and emphasis of this committee on informed consent is unique, and that the development of an informed consent teaching process for residents will focus on the moral and ethical issues regarding informed consent. Even more important, we believe we will emphasize the patient care aspects of informed consent and also teach residents their responsibilities for long-term patient care with regard to patients' satisfaction and understanding of their disease process. PMID- 2911765 TI - Cocaine-associated rhabdomyolysis and acute renal failure. AB - We have described four male patients, aged 21 to 39 years, who had rhabdomyolysis and acute renal failure during parenteral cocaine use. This complication has only recently been attributed to cocaine. Their illnesses behaved clinically like nonoliguric acute tubular necrosis, though renal biopsies were not done. No permanent nerve, muscle, or kidney damage resulted. PMID- 2911766 TI - Avulsion of the nongravid uterus due to pelvic fracture. AB - I have reported the case of a 21-year-old woman who was thrown from her car, sustaining multiple severe closed pelvic fractures with avulsion of the uterus at the corpocervical junction. Laparotomy showed massive hemoperitoneum due to avulsion of the uterus. After subtotal hysterectomy, she was placed in skeletal traction, and later had open reduction and internal fixation with a cancellous iliac bone graft. At two-month follow-up, she was ambulatory on crutches, and x ray films showed a stable pelvis with healing of the fractures. PMID- 2911767 TI - Stercoraceous perforation of the right colon. AB - We have reported a case of stercoraceous perforation of the right colon with peritonitis. Stercoraceous perforation should be considered in patients with an acute condition of the abdomen, radiologic evidence of a perforated viscus, and a long-standing history of constipation. The condition is rare and has a high mortality. The treatment of choice is always surgical. PMID- 2911768 TI - Health perceptions and medical care opinions of inner-city adults with sickle cell disease or asthma compared with those of their siblings. AB - Inner-city adults (n = 108) with a chronic disease (sickle cell disease or asthma) and their unaffected siblings (n = 50) were interviewed and ratings of health perceptions and opinions about medical care were compared. Persons with a chronic disease reported unfavorable ratings of their health (P less than .001). Their siblings reported moderately favorable health perceptions but much worry and concern about their health. When compared with the asthma subgroup, persons with sickle cell disease reported more adverse ratings of health outlook susceptibility to illness, sickness orientation, humaneness of medical care, and satisfaction with medical care (P less than .05). These observations demonstrate low health perceptions in adults with two chronic medical conditions and more negative perceptions in persons with sickle cell disease. They indicate possible opportunities for improving medical care for patients with these conditions to achieve better perceptions of health, outlook, and medical services. PMID- 2911769 TI - Pellegrini-Stieda syndrome mimicking acute septic arthritis. AB - This case illustrates the potential severity of an uncommon and generally benign condition of the knee--the Pellegrini-Stieda syndrome. The regional bone scan clearly showed the etiologic role of the inflamed ligamentous attachment site. Therapy should include joint rest, nonsteroidal anti-inflammatory agents, and possibly ice for symptomatic relief. PMID- 2911770 TI - Resolution of secondary amyloidosis 14 years after adequate chemotherapy for skeletal tuberculosis. AB - Despite available chemotherapy, survival of patients with skeletal tuberculosis and secondary amyloidosis for more than five years is extremely unusual. We have described a patient with inadequately treated tuberculous osteomyelitis and later concomitant pulmonary tuberculosis and secondary amyloidosis. After a prolonged course of antituberculous chemotherapy, the patient was found to be cured of the tuberculosis and to have complete resolution of the amyloidosis 14 years after the diagnosis. PMID- 2911771 TI - A simple test for detecting CSF. PMID- 2911772 TI - Listeria monocytogenes sepsis from an infected indwelling i.v. catheter in a patient with AIDS. PMID- 2911773 TI - Coronary thrombolysis in rural hospitals. PMID- 2911775 TI - Trauma, the scourge of modern society. PMID- 2911774 TI - Use of NSAIDs in long-distance runners: a risk factor for sudden death? PMID- 2911776 TI - An assessment of framelapse videography of the effect of cryopreservation on human sperm motility. AB - Sixteen sperm specimens collected from regular healthy donors at Groote Schuur Hospital Sperm Bank were assessed subjectively by phase contrast light microscopy and the results were compared with assessments made by framelapse videography. The same specimens were frozen and thawed and re-assessed by framelapse videography and the results compared with the pre-freeze assessments. The objective cryosurvival was found to be 53%. The subjective assessment varied by an average of 20% from the videographic method. Framelapse videography was found to be a practical reproducible method for assessment of sperm motility where accuracy is essential. PMID- 2911777 TI - Seminal carnitine, epididymal function and spermatozoal motility. AB - The carnitine content of semen from azoospermic subjects and subjects with either impaired motility or forward progression is reported. Within the azoospermic group, the values were not significantly different between those with testicular failure or obstruction. The patients with impaired motility (less than 40%) or impaired forward progression (less than 3) had a lower mean seminal carnitine content than those with good motility and forward progression (P less than 0.05). Seminal carnitine concentration was not an index of epididymal patency and could not be regarded as useful for locating the level of obstruction in the epididymis. Since carnitine plays an important role in the maturation process when sperm acquire motility, it would seem that seminal carnitine might be an indicator of epididymal dysfunction. PMID- 2911778 TI - Changes in sperm motility, morphology and concentration induced by the swim-up procedure. AB - Fifteen semen samples from normal donors were washed twice in Earle's medium by centrifugation and allowed to swim up into overlayered Earle's medium. Aliquots of 0.2 ml were drawn before and after the swim-up, for assessment of sperm motility, morphology and concentration. The percentage of sperm showing progressive motility improved by an average of 54.02 +/- 45.97%, and sperm with the normal morphology increased by 63.8 +/- 31.01%. Head and tail abnormalities decreased by 47.17 +/- 21.3% and 89.37 +/- 16.1% respectively. There was no statistical change in acrosomal abnormalities. Sperm concentration was reduced by 89.02 +/- 7.4%. It is concluded that the standard swim-up technique resulted in an overall improvement in sperm quality, but that the technique was not effective in reducing the acrosomal abnormalities. PMID- 2911779 TI - Influence of the swim-up procedure on acrosome damage induced by freezing human semen. AB - Twenty frozen semen samples from normal donors were thawed, washed in Earle's medium, and allowed to swim up using standard techniques. The samples were evaluated before and after the swim up for progressive motility and concentration. Morphologically normal sperm were assessed for acrosomal integrity according to the relative percentages of normal, damaged or lost acrosomes. The motility improved by 75.07 +/- 90.38%, the count was reduced by 97.1 +/- 1.9%, but there was no significant change in the frequencies of the different types of acrosome state. It was concluded that although the swim-up technique is successful in reducing most major morphological abnormalities, influence over the frequencies of secondary acrosomal abnormalities could not be demonstrated. PMID- 2911780 TI - [By his letters shall the doctor be known]. AB - The furnishing of information by doctors who refer patients to a hospital, be it by telephone or by letter, is of the greatest importance. Unfortunately, there are a great many doctors who underestimate the value of this serious responsibility towards the patient and as a result provide no or insufficient data. PMID- 2911781 TI - [Symptomatic treatment of the malignant carcinoid syndrome with octreotide]. AB - Intractable diarrhoea and flushing due to the malignant carcinoid syndrome is seldom relieved by conservative medical treatment. Octreotide (Sandostatin; Sandoz) is a long-acting analogue of somatostatin and a powerful inhibitor of endogenous peptide release. A patient with severe diarrhoea and flushing due to the malignant carcinoid syndrome, in whom symptomatic control with octreotide was achieved, is described, and the value of octreotide treatment in the malignant carcinoid syndrome is discussed. PMID- 2911782 TI - Why marathon runners collapse. PMID- 2911783 TI - Haematological reference values in adult blacks at sea level. PMID- 2911784 TI - Nasomaxillo-acrodysostosis. AB - Thirteen patients with nasomaxillo-acrodysostosis are described. Some have the facial appearance of this syndrome only, although the others are more severely affected, with skull, eyes, ears, vertebrae and peripheral extremity involvement. The features of the 13 patients were studied and compared with those described in the literature as belonging to 'maxillonasal dysostosis' and 'acrodysostosis'. It seems certain that there is in fact only one syndrome, which differs only in extent of involvement. PMID- 2911785 TI - Thoracic trauma. PMID- 2911786 TI - Epidemiology of chest trauma. AB - Chest trauma ranks third behind head and extremity trauma in major accidents in the United States. The motor vehicle accident is the most common etiology (70 per cent). Within the thorax, the chest wall itself is the most often injured. Many of these injuries are of moderate severity and rarely require surgical intervention. The majority of chest trauma requires careful surveillance to identify those patients who require operative correction. Improvement in vehicle safety, moderation of speed, and continued education should reduce the incidence and severity of chest trauma. PMID- 2911787 TI - Pulmonary contusion. Evaluation and classification by computed tomography. AB - In thoracic trauma, as in all of medicine, diagnosis precedes therapy. Over the past 5 years, we have liberally used chest CT examinations to improve diagnosis in the severely injured patient. This approach has significantly increased our diagnostic yield and permitted early diagnosis and treatment of unsuspected injuries. Confidence in our method of quantitation has helped us to assess the severity of pulmonary parenchymal injuries. Correlation of the CT findings with histologic study has changed our concept of pulmonary contusion from that of interstitial disease to that of pulmonary laceration with blood pneumonia. PMID- 2911788 TI - Cannulation of inferior vena cava for long term central venous access. AB - Nineteen patients had a Silastic (silicone rubber) catheter placed into the inferior vena cava (IVC) by way of a vein of a lower extremity. All patients needed long term venous access but had conditions precluding access to the superior vena cava (SVC) or access sites of the upper torso. Precautions regarding operative technique for the placement of the catheter include incisions through healthy skin, maintenance of aseptic technique at the site of access, an atraumatic subcutaneous tunnel at least 25 centimeters in length and a long acting local analgesic effect. Catheters were in situ for a total of 2,215 days (a mean of 111 days per catheter). Catheters were also used to administer intravenously medications, blood and blood products, chemotherapeutic agents, parenteral nutrition and for sampling of blood. Four complications occurred: one instance each of catheter sepsis and infection of the subcutaneous tract and two of thromboses of the IVC. No deaths occurred. The complication rate was 0.18 per cent per catheter-day. Long term access to the IVC is feasible without undue concern in conditions in which access to the SVC is precluded but long term central access is essential. PMID- 2911789 TI - Late results of immediate primary end to end repair in accidental section of the common bile duct. AB - The late results of 43 patients with accidental section of the common bile duct are presented. Injuries located high at the hepatic duct were three times more frequent than those located more distally. A complete section occurred in 36 while incomplete section was observed in seven patients. The final results of end to end repair revealed good late results in eight while 29 had a benign stricture four years postoperatively. PMID- 2911790 TI - Massive splenomegaly. AB - A 16 year review of 391 splenectomies performed at New England Medical Center was done to evaluate the morbidity and mortality of patients with drained splenic weights greater than 1,000 grams. Thirty-six met the criteria for study. Twenty men and 16 women with an average age of 55.4 years were identified. Myeloproliferative disorders were the most predominant cause of massive splenomegaly. Pancytopenia and hemolytic complications of the disease processes were the most acute indications for operations. The average time between diagnosis and operative intervention was 42 months. An average of 10 units of blood products were required to correct preoperative coagulopathy. Eleven of 36 patients had postoperative complications. Eight of 21 with drains and an equal number of patients with preliminary splenic arterial ligation had complications. Eight-one per cent of all complications were infection related. Complication increased the length of stay 11 days. The 30 day mortality rate was 11.1 per cent. Sepsis was the major cause of mortality. Closed drainage system provided no demonstrable benefit nor appeared to be the cause of sepsis. No episodes of pulmonary embolic phenomenon or peripheral venous thrombosis were demonstrated. Elective splenectomy in patients with smaller spleens was performed without operative mortality and with 3 per cent morbidity rate. For patients with massive splenomegaly, the average survival time was 28.5 months. The majority of these patients died from complications of the disease. Preoperative coagulopathy, failure to demonstrate a hematologic response to splenectomy and reoperation were clear predictors for decreased long term survival periods.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2911791 TI - An experimental study of susceptibility to infection after hemorrhagic shock. AB - Hemorrhagic shock has been associated with an increased risk of infection after injury. The immediate and long term effects of hemorrhagic shock without tissue injury on the susceptibility of an animal to infection and the efficacy of antibiotic prophylaxis to prevent infection in this setting were examined. Sprague-Dawley rats were subjected to hemorrhagic shock (LD15) by bleeding to a mean arterial pressure of 45 millimeters of mercury for 45 minutes and were resuscitated with shed blood and normal saline solution. In one experiment, dorsal wounds were inoculated one hour before or after shock with either 10(6), 10(8) or 10(10) Staphylococcus aureus. In a second experiment, rats were infected at one hour, or one, three or five days after shock with 10(6), 10(7) or 10(8) S. aureus. Equivalent numbers of rats received cefamandole nafate prior to bacterial challenge. Hemorrhagic shock increased the susceptibility to wound infection at all inocula. Infection increased whether rats were wounded before or after shock, and this effect was sustained for up to three days. Antibiotic prophylaxis was of limited value in reducing the incidence of wound infection after shock. PMID- 2911792 TI - Hemodynamic and metabolic alterations during experimental sepsis in young and adult rats. AB - Cecal ligation and puncture (CLP) has been extensively used as a model of sepsis in adult rats. It is not known if the response to sepsis is similar in young and adult rats. This investigation was done to compare hemodynamic and metabolic alterations in young (four to six weeks of age, 60 to 90 grams) and adult (12 to 14 weeks of age, 270 to 340 grams) rats after CLP. In one series of experiments, survival rate was determined for 96 hours, and in other experiments, mean arterial blood pressure (MAP), heart rate (HR), white blood cell count, hematocrit, platelets, plasma glucose, lactate, amino acids, blood urea nitrogen (BUN), blood and peritoneal cultures and resting energy expenditure (REE) were determined eight and 16 hours after CLP. Levels of glycogen in liver and muscle were determined 16 hours after CLP. Mortality rate was similar in young and adult rats. MAP was stable throughout the course of sepsis, with no significant differences between the two groups of rats. HR was higher in young rats at all times studied. The adult rats became hyperglycemic after CLP while the young were hypoglycemic eight hours after CLP but normalized at 16 hours. Plasma lactate and BUN were similar in the two groups of rats, and no alterations were seen during sepsis. Both young and adult rats became hypoaminoacidemic after CLP. The phenylalanine to tyrosine ratio increased in a similar manner during sepsis in both experimental groups. REE was higher in young than in adult rats, but no significant changes were observed during the course of sepsis in either group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2911793 TI - Resectional surgical procedures for carcinoma of the head of the pancreas. AB - Of a total series of 103 patients with preoperatively diagnosed carcinoma of the head of the pancreas (including ampullary carcinoma, carcinoma of the distal part of the common bile duct and pancreatic duct and acinar cell carcinoma), 78 underwent pancreatic resection. The remaining 25 had palliative surgical treatment, either a gastric or biliary bypass, and are not included in the present study. Three of the 78 patients who underwent pancreatic resection died, and ten patients required early reoperation. Predictive criteria could be formulated for the prognosis and outcome of the patients with carcinoma of the head of the pancreas. The most reliable index for survival time of the patients proved to be the radicality of the resection, which was directly related to the differentiation of the primary tumor. Forty-three of 48 patients who underwent radical resection are alive, with a survival time ranging from three to 49 months. Eleven of 23 patients who underwent palliative resection are alive, with a survival time ranging from two to 29 months. Of 44 patients with well or moderately differentiated adenocarcinoma who underwent radical resection, 38 are alive, with a survival time ranging from six to 41 months (mean of 29 months). PMID- 2911794 TI - A multidisciplinary approach to reducing morbidity and operative blood loss during resection of carotid body tumor. AB - Seven carotid body tumors in six patients were successfully managed using a multimodality approach that included the vascular surgeon, head and neck surgeon and angiographer. Five tumors were managed with preoperative subselective embolization of tumor vessels. Two required vascular reconstruction. The mean operative blood loss was 332 milliliters. All of the patients survived, and the only morbidity was one instance of transient vocal cord paresis. Surgical resection remains the treatment of choice for carotid body tumors. After angiographic embolization, a combined surgical approach by both the vascular surgeon and the head and neck surgeon reduces the associated morbidity and blood loss during resection. PMID- 2911795 TI - Percutaneous endoscopic gastrostomy made easier. AB - The use of a Fogarty catheter instead of a silk suture in performing an endoscopic gastrostomy offers several advantages. It avoids the problems of stomach deflation, the stomach slipping off the intravenous cannula, the troublesome passage of a soft suture through a small caliber tube and grasping a soft mobile object in the stomach. PMID- 2911796 TI - Supraceliac aortorenal bypass with saphenous vein for renovascular hypertension. PMID- 2911798 TI - Combined endoscopic and fluoroscopic balloon dilatation of a complex proximal jejunal stricture. AB - Dilatation of esophageal strictures has been practiced for many years. More recently, balloon dilatation, with endoscopic guidance, has been applied to the stomach and the colon. The small bowel has been less accessible to the endoscope, and, as far as we have been able to determine, balloon dilatation of jejunal strictures has not been reported. We present a patient who was referred to us after curative resection of two abdomino-pelvic malignancies, external beam irradiation to the abdomen and pelvis, and multiple later operations for bowel obstruction and dehiscence of intestinal anastomoses. The bowel obstruction and anastomotic dehiscence occurred during the present hospitalization and resulted finally in the development of a high-output proximal jejunal fistula. The area of stricture, as seen by means of barium contrast, had two separate components with an associated acute angulation. We report the combined use of endoscopic and fluoroscopic manipulation and balloon dilatation of this complex stricture. PMID- 2911797 TI - Optimal hypothermic preservation of arrested myocardium in isolated perfused rabbit hearts: a 31P NMR study. AB - The purpose of this study was to (1) relate myocardial high-energy phosphate stores to functional recovery after ischemia and reperfusion, (2) assess the bioenergetics and functional influence of clinically relevant myocardial hypothermia, and (3) examine tissue pH as an independent indicator of postischemic recovery of function. Rabbit hearts were perfused via a modified Langendorff technique, monitored for developed pressure (DP) and left ventricular end-diastolic pressure (LVEDP) via an isovolumic left ventricular balloon catheter, and placed in a Brucker NMR magnet (4.7 tesla) to measure phosphocreatine (PCr), adenosine triphosphate (ATP), and pH. Hearts underwent 1 hour of global ischemia at 7 degrees, 17 degrees, 27 degrees and 37 degrees C initiated by one dose of K+ cardioplegia followed by 30 minutes of reperfusion. After reperfusion, DP (expressed as a percentage of preischemic control) and LVEDP (mm Hg) in 7 degrees and 17 degrees C hearts were no different (96 + 5% vs 97 +/- 3%; 5 +/- 2 mm Hg vs 6 +/- 2 mm Hg; p = NS), but were better (p less than 0.01) than 27 degree hearts (72 +/- 6%, 17 +/- 6 mm Hg) and 37 degree hearts (31 +/- 7%, 60 +/- 6 mm Hg). PCr was severely depleted in all groups. ATP was 90 +/- 7% and 87 +/- 5% of preischemic control in the 7 degree and 17 degree hearts, which was significantly better than the 68 +/- 3% and 21 +/- 3% in the 27 degree and 37 degree groups (p less than 0.01). The pH at end ischemia was 6.83, 6.89, 6.54, and 5.86 for the 7 degree, 17 degree, 27 degree, and 37 degree hearts, respectively (7 degrees vs 27 degrees or 37 degrees, p less than 0.01; 17 degrees vs 27 degrees or 37 degrees, p less than 0.01). Linear regression of DP on end ischemic ATP (EIATP) and end-ischemic pH revealed: DP = 0.96 (EIATP) + 20 (r = 0.92) and DP = 60 (pH) -317 (r = 0.86). We conclude that (1) end-ischemic ATP predicts recovery of ventricular function, and, furthermore, there appears a threshold ATP concentration (80% of control) below which full recovery of function will not occur; (2) end-ischemic pH predicts recovery of ventricular function; (3) 7 degrees C hypothermic ischemia does not cause a clinically significant cold injury; and (4) in a single-dose crystalloid cardioplegia model, end-ischemic pH is linearly related to recovery of function (r = 0.86). PMID- 2911799 TI - High-compression elastic stockings. PMID- 2911800 TI - Aortoiliac reconstruction. PMID- 2911801 TI - Histologic features predictive of an increased risk of early local recurrence after treatment of breast cancer by local tumor excision and radical radiotherapy. AB - A histopathologic review was undertaken of 293 patients with breast cancer treated by local tumor excision and radical radiotherapy. In a 6-year period, there were 37 local treatment failures with 16 deaths, and an additional 20 patients died without local recurrence. Pathologic data were available for 272 patients. Multivariate analysis indicated that the pathologic features in an invasive tumor most predictive for local recurrence were the combination of a high proportion of intraduct carcinoma with extensive necrosis (comedocarcinoma). Of 18 patients with these features, nine have had early local recurrence (a risk of 50% with these features vs 10% in those without), and four have died (a risk of 22% against 12%). Despite the short follow-up, the results already appear significant, and the study is ongoing. The importance of comedonecrosis in the intraduct component as a prognostic indicator in invasive carcinoma of the breast is not widely recognized and might constitute a relative contraindication to conservative treatment of the breast. PMID- 2911802 TI - Exposure of the left hepatic duct through the hilum or in the umbilical of the liver: anatomic limitations. AB - Anastomosis to the left hepatic duct approached by dissecting the hilar plate is the most reliable method of drainage of the left side of the liver in that longitudinal incision of the left hepatic duct allows a long cholangiojejunostomy. However, the anatomy is not satisfactory in 30% of cases for adequate drainage of the left side of the liver. To further clarify this surgically important area, 107 vasculobiliary casts were reviewed with regard to the anatomy and relationship between the left biliary ductal and left portal venous systems. In cases in which anatomy is unfavorable for adequate drainage by anastomosis to the left hepatic duct in the hilum, several options are available. The anterior portion of the main portal fissure may be opened to gain wide access to the superior aspect of the biliary plate and reach a posterior duct that is more suitable for anastomosis. An anastomosis to an anterior duct may also be possible with this approach. If left portal ducts are inaccessible by division of the main portal fissure because of a retroportal location, then an anastomosis in the anterior portion of the umbilical fissure may give adequate drainage. Therefore a cholangiogram is imperative before any anastomosis in the hilum or the anterior portion of the umbilical fissure. PMID- 2911803 TI - Fatigue and cardiac and endocrine metabolic response to exercise after abdominal surgery. AB - Subjective feeling of fatigue was quantified before and 20 days after elective uncomplicated abdominal surgery in 16 otherwise-healthy patients and compared with changes in heart rate and various hormonal and substrate responses to a 10 minute bicycle exercise (65% of preoperative maximal work capacity) preoperatively and postoperatively. Postoperatively, fatigue increased (p less than 0.001) from 3.0 +/- 0.5 to 5.3 +/- 0.5 arbitrary units (mean +/- SEM). Heart rate, plasma catecholamines, and serum growth hormone, lactate, alanine, and glycerol values always increased, whereas serum insulin values decreased in response to exercise (p less than 0.01). During exercise, only heart rate (p less than 0.01) and lactate (p less than 0.05) values were higher postoperatively compared with preoperatively. Increase in fatigue postoperatively correlated significantly to increase in heart rate (p less than 0.01) and correlated positively, but not significantly, to increase in plasma levels of noradrenaline (p = 0.08), growth hormone (p = 0.09), and alanine (p = 0.08) during exercise, but not to increase in serum lactate values (p greater than 0.8). Thus, after uncomplicated surgery, there was increased fatigue and amplified metabolic and cardiovascular response to a given absolute work load. These findings are similar to those observed during detraining and suggest a therapeutic role of exercise in the treatment of postoperative fatigue. PMID- 2911804 TI - Large bile duct stones treated by endoscopic biliary drainage. AB - One hundred five patients with obstructive jaundice and cholangitis (49 patients), referred for diagnostic endoscopy, were found to have inextractable bile duct stones. Median age was 76 years and three quarters were more than 72 years of age. Insertion of an endoprosthesis with or without a sphincterotomy relieved jaundice in 94% and settled cholangitis in 90%. Antibiotic cover during the procedure seems essential inasmuch as pyrexia and septicemia occurred in 6 of 57 cases where it was not given. One case was lethal. Another patient died of acute pancreatitis. The patients were old. One quarter died before the follow-up, 1 to 5 years after the initial intervention. The results indicate that the combination of endoscopic sphincterotomy, insertion of an endoprosthesis, and, if feasible, stone extraction on a later occasion when the acute phase of the illness had subsided brought the disease sufficiently under control among three quarters of the patients with large common duct stones or stenoses in the biliary tract. One quarter of the patients were treated surgically. This was accomplished without mortality, but morbidity was not negligible. A policy with a surgical approach restricted to selected cases with persistent symptoms in spite of sufficient endoscopic drainage is recommended. PMID- 2911805 TI - Crystalloid versus colloid fluid resuscitation: a meta-analysis of mortality. AB - Controversy persists over the best choice of fluid to use for resuscitation. A number of published articles promote the use of either colloid or crystalloid fluids. Most of the arguments for use of one fluid or the other are based on cardiopulmonary data collected during and after fluid resuscitation. Although many studies report the mortality rate of patients treated with both fluids, none have critically analyzed this most important aspect of therapy. Meta-analysis is a relatively new statistical method whereby data from a number of clinical trials can be pooled to produce more reliable data. In this study meta-analysis was used to pool mortality data from reports of eight previously published, randomized, clinical trials, in which the efficacy of crystalloid and colloid fluid resuscitation was compared. The overall treatment effect when the data from all the clinical trials were pooled showed a 5.7% relative difference in mortality rate in favor of crystalloid therapy. When the data from only those studies using trauma patients were pooled, the overall treatment effect showed a 12.3% difference in mortality rate in favor of crystalloid therapy. However, when data from studies that used nontrauma patients were pooled, there was a 7.8% difference in mortality rate in favor of colloid treatment. In patients with trauma who are septic and in whom the capillary leak syndrome leads to adult respiratory distress syndrome, it may be assumed that colloid resuscitation would be no better than crystalloid resuscitation. In this study the meta-analysis of published data showed that this form of treatment is deleterious. In patients who are nonseptic or having elective surgery, however, the basement membrane is intact, and meta-analysis of data in this setting showed that treatment with colloids would be efficacious. PMID- 2911807 TI - Texas' nursing shortage: situation & solutions. PMID- 2911806 TI - Self-rated psychiatric symptoms in patients operated on because of primary hyperparathyroidism and in patients with long-standing mild hypercalcemia. AB - Self-rated psychiatric symptoms were investigated in 30 patients referred for surgery because of primary hyperparathyroidism (HPT) (serum calcium, 2.87 +/- 0.21 mmol/L) in 38 subjects detected in a health screening, with 15 years of mild hypercalcemia and probable HPT (serum calcium, 2.66 +/- 0.09 mmol/L), and in 38 normocalcemic control subjects. The psychiatric symptomatology was evaluated by use of the Hopkins Symptom Checklist (HSCL-56), a self-rating symptom scale. The patients with verified HPT had the highest mean HSCL score, 89.1 +/- 20.1 before surgery, compared with 76.6 +/- 17.0 (p less than 0.01) in the health survey hypercalcemic patients and 73.8 +/- 16.0 (p less than 0.001) in the controls. The factors for anxiety, depression, and cognitive symptoms were the most pronounced in the HPT patients and were also increased among the mildly hypercalcemic persons of the health survey, compared with the controls. Somatic symptoms such as headache, back pain, chest pain, and weakness were equally common in HPT and in the controls, and measurements of isometric muscle strength of knee extension did not demonstrate reduction of muscle strength in the health survey hypercalcemic patients. Follow-up of the HPT patients 1 year after parathyroid surgery revealed a marked improvement in mental health (HSCL score 73.2 +/- 13.7, p less than 0.001). In the health survey hypercalcemic patients, neither the psychiatric symptomatology nor the muscle strength were influenced by 6 months of oral vitamin D therapy (alphacalcidol). The results demonstrate that psychiatric symptoms are experienced frequently by patients with HPT and minimum to moderate increases in the serum calcium level and that these disturbances are reversed by parathyroid surgery. PMID- 2911808 TI - National Commission reports: nurses yearn time for nursing. PMID- 2911809 TI - [Hospitals and primary health care]. PMID- 2911810 TI - [Day surgery--yesterday and today]. PMID- 2911811 TI - [Vascular surgery in Norway]. PMID- 2911812 TI - [Vascular surgery in Norway in 1986]. AB - A questionnaire on vascular surgical activity in 1986 was sent to all Norwegian surgical departments (80). 78 units responded. Vascular surgery is not performed in the two hospitals who did not respond. Altogether 3,509 vascular operations were performed in 1986 (844 operations per million inhabitants). By comparison, 2,529 operations were performed in 1981, 2,039 in 1978 and 1,100 in 1975. The largest increase was recorded in operations for abdominal aortic aneurysm, carotid artery stenosis, arterial emboli and angio-access surgery. Elective vascular operations were performed in 41 departments, whereas an additional 16 did emergency vascular surgery only. 34% of the operations were performed by members of the junior staff. Differences between the five health regions have decreased since the investigation in 1981. The highest activity was observed in Health Region V, where 986 operations were performed per million inhabitants. Vascular surgical activity is increasing in Norway. This must be taken into account when estimating the number of residencies and staff positions for vascular surgery. The increasing need for vascular surgery should also influence priorities in our national health system. PMID- 2911813 TI - [Insurance and cancer. Low utilization of contributions]. PMID- 2911814 TI - [An epidemic of ectopic pregnancies in Ostre Akershus. Looking for possible causes]. AB - During the period 1969 to 1985, 640 women with a confirmed diagnosis of ectopic pregnancy were admitted to Sentralsykehuset i Akershus. The case histories were reviewed for possible predisposing factors. From 1969 to 1985 the frequency of ectopic pregnancy increased threefold in relation to the number of conceptions in the same region. Until 1978 the major part of this increase was observed among women with IUCD in situ. Women who had previously undergone surgery on the uterine tubes accounted for the greater part of the increase in extrauterine pregnancies after 1976. A large year-to-year variation was found among women with neither of the above predisposing factors. However, a rising frequency of ectopic pregnancies was also observed in this group. It appears that the risk of ectopic pregnancy is greater among women using IUCD than among women using other methods of contraception. PMID- 2911815 TI - [Isolation of Staphylococcus in Northern Norway. Identification and effects of antibacterial agents]. AB - 53 Staphylococcus aureus and 100 Staphylococcus epidermidis consecutive routine isolates were collected from hospitalized (H) and non-hospitalized (NH) patients in Northern Norway. A coagulase slide test for rapid identification of the cell bound coagulase of S. aureus was just as sensitive as slower tests such as the tube test for free coagulase, anaerobic acid production from mannitol, and the DNase test. Close to 80% of S. aureus isolates showed beta-lactamase production. There was no difference in sensitivity between S. aureus strains isolated from H patients and NH patients respectively. All strains were sensitive to erythromycin, oxacillin, cephalothin, tetracyclin, trimethoprim, gentamicin, clindamycin, vancomycin, and rifampicin. Most isolates showed strong sensitivity to other cephalosporins than cephalothin (although less sensitive to 3. generation cephalosporins), fucidic acid and chloramphenicol. Thus, with exception of the first generation penicillins, in our region S. aureus is still strongly sensitive to most antimicrobial agents used both in hospital and in ambulatory practice. Approximately 50% of the 68 S. epidermidis isolates from urine showed beta-lactamase activity, as against almost 80% of other clinical specimens. Urine isolates were fairly often trimethoprim resistant (29.4%) and had a slightly higher resistance than S. aureus had to several antimicrobial agents. There was no difference in the resistance pattern among urinary isolates from H patients and from NH patients respectively. S. epidermidis isolates from 32 other clinical specimens from H patients showed a substantially higher pattern of resistance compared with urine isolates. Resistance against gentamicin was found in 40.6%, and against oxacillin in 9.4%. Gentamicin resistant strains were also resistant to several other broad spectrum agents. All strains were highly sensitive to vancomycin and clindamycin. PMID- 2911816 TI - [Diathermy in surgery]. AB - Unskilled handling of surgical diathermia units exposes patients, operators and assistants to unnecessary risks. This article briefly reviews the equipment's technical potential, possible risks of complication, and how risk factors can be eliminated by proper handling. Important issues are risk of local accidental burns and of unintended stimulation of muscles and nerves, precautions when treating patients with a pacemaker or metallic implant, and specific problems connected to endoscopy. PMID- 2911817 TI - [Surgical treatment of pancreatic injuries]. AB - Major pancreatic traumas are not frequent, and diagnosis often difficult. In a retrospective study we found 11 verified cases of pancreatic trauma treated in the period 1977-86. Three were penetrating and eight blunt trauma victims. Five patients suffered serious lesions in other organs. Laparotomy was performed in nine patients. One patient died, due to other lesions. The patients can be separated clinically into two groups. In the first group emergency laparotomy is indicated because of bleeding or peritonitis, most often due to lesions in other abdominal organs. In the other group the initial symptoms and clinical signs are sparse, and the diagnosis is based on repeated clinical examinations, ultrasound CT, peritoneal lavage and repeated amylase determinations. Contusions and minor lacerations without injury to the duct are treated with revision and canalization. Resection and pancreatico-jejunostomy should be considered when the pancreas is heavily lacerated with damage to the duct system. PMID- 2911818 TI - [Heterosexual transmission of HIV--a predominantly female problem?]. AB - Heterosexual dissemination of HIV is increasing in Norway. Women are apparently more exposed than men. 70% of Norwegian HIV-cases attributed to domestic heterosexual transmission are women. The two groups of sexual partners that most frequently infect Norwegian women with HIV are drug abusers and men from countries with a high prevalence of the disease. Physicians ought to be aware of this increase in heterosexual HIV-contamination, especially among younger women, so that they can undertake the public-health measures needed to delimit the spread of the disease. In particular, they should include sexual anamnesis in their examination of all cases where HIV-infection is a possibility. PMID- 2911819 TI - [A questionnaire study of day care. Big differences and unused possibilities among Norwegian hospitals]. AB - We have studied the use of day care surgery in surgical, gynecological and ENT departments in Norwegian hospitals. A questionnaire was sent to 129 departments at 79 hospitals. The response rates were 95.3% and 98.7%. We asked about 28 diagnoses and procedures and whether day care surgery was used systematically. We also asked how day care surgery was organized, how the operations were registered, how the patients were informed about the different procedures and if they had to pay part of the fee themselves. Many departments always hospitalize patients for minor and intermediate surgery, and there are big differences between the hospitals in regard to the extent of day care surgery. Many hospitals do not make full use of available resources because day care surgery is not organized as an alternative to hospitalization. PMID- 2911820 TI - [Day care. A seminar about why and how]. AB - We describe a seminar on day care surgery and give a summary of the lectures and discussions. Updated waiting lists, good administration of waiting lists, and good planning of the operations are important for successful day care surgery. Many departments hospitalize patients for minor and intermediate surgery, such as hernia and varicose veins, which could have been treated by day care surgery. The general health of the patients and their social conditions are important when choosing between day care surgery and hospitalization. The distance to the hospital and the patients' age are less important. It is essential to inform the patients properly about the procedures. Day care surgery gives good medical results and a high quality of care at lower cost than hospitalization. Patients who can be treated by day care surgery should be given this opportunity. PMID- 2911821 TI - [Salt and blood pressure--one more time]. PMID- 2911822 TI - Validity of cerebral arterial blood flow calculations from velocity measurements. PMID- 2911823 TI - Effect of nimodipine on canine cerebrovascular responses to 5-hydroxytryptamine and potassium chloride after exposure to blood. AB - The stainless steel cannula inserting method was used to investigate the blocking effects of nimodipine on vascular responses to intraluminal administration of 5 hydroxytryptamine (5-HT) or potassium chloride (KCl) before and after application of abluminal blood containing thrombin in isolated and perfused canine basilar arteries. A transient elevation of perfusion pressure was observed initially, and during the course of the experiment the perfusion pressure gradually increased. Nimodipine significantly depressed both transient and prolonged changes of perfusion pressure. Dose-dependent vasoconstriction induced by 5-HT was significantly enhanced, while that evoked by KCl was significantly attenuated for up to 8 hours after the application of blood. Pretreatment with nimodipine inhibited vasoconstriction to 5-HT less effectively than to KCl both before and after application of blood. The proportion of the 5-HT-induced vasoconstriction, which was sensitive to nimodipine, was reduced after application of blood, while no such change was observed in the responses to KCl. It is suggested that the augmentation of cerebrovascular responses to 5-HT in the early stage of subarachnoid hemorrhage may be mediated mainly by changes in intracellular calcium utilization rather than by the increase of calcium influx through nimodipine-sensitive channels. PMID- 2911824 TI - Model of electrocardiographic changes seen with subarachnoid hemorrhage in rabbits. AB - We developed a new method for introducing drugs into the basal cistern of rabbits. With minimal surgical invasion, we used either the opening of the craniopharyngeal duct to access the chiasmatic cistern or the suture between the basisphenoid and basioccipital bones to access the interpeduncular cistern. With our method, 0.5 ml contrast medium injected into three rabbits was determined roentgenographically to remain in the basal cistern; histologically, all the brain tissue remained intact. Intracisternal injection of 0.5 ml physiological saline into five rabbits had no effect on the cardiovascular system. In 23 rabbits, injection of 0.5 ml 0.1% prostaglandin F2 alpha led to a variety of electrocardiographic changes, including sinus bradycardia (in 43.5%), premature atrial contractions (in 17.4%), and premature ventricular contractions (in 39.1%). In 15 rabbits with severe changes, arrhythmia was followed by ST depression (in 30.4%), ST elevation (in 8.7%), T wave inversion (in 4.3%), ventricular tachycardia (in 17.4%), or ventricular fibrillation (in 4.3%). Intracisternal injection of 0.5 ml 1.0% lidocaine into the 23 rabbits was very effective in overcoming bradycardia and arrhythmias. We conclude that the clinical features of electrocardiographic changes seen in patients with subarachnoid hemorrhage are reproducible in this rabbit model. PMID- 2911825 TI - Effect of lidocaine on forebrain ischemia in rats. AB - We examined the effect of lidocaine on ischemic neuronal injury in the rat forebrain ischemia model. Cerebral ischemia was achieved with bilateral carotid artery occlusion and controlled hypotension to a mean of 50 torr for 10 minutes. Perfusion-fixation was performed 7 days after ischemia, subsequent to which the brains were sectioned coronally and stained with hematoxylin and eosin. Ischemic neuronal injury was quantitatively expressed (after direct counting) as a percentage of total neurons, that is, ischemic neurons divided by (ischemic neurons + normal neurons). Predictably, the selectively vulnerable hippocampal areas exhibited the most marked neuronal injury. In the CA1/CA2 sectors, lidocaine-treated rats demonstrated less injury (34 +/- 14%) than untreated (64 +/- 9%) or saline-treated (70 +/- 10%) rats. However, these superficially pronounced numerical differences were not of statistical significance (p greater than 0.05). In the CA3 sector, neuronal injury in lidocaine-treated rats (31 +/- 14%) was significantly different at p less than 0.05 from the untreated (80 +/- 5%) but not the saline-treated (59 +/- 13%) group. We conclude that lidocaine may have an only marginal beneficial effect on forebrain ischemia in rats. PMID- 2911826 TI - Extracranial carotid artery disease in patients with arterial limb embolism. PMID- 2911827 TI - Multiple small-vessel occlusions in systemic lupus erythematosus. PMID- 2911828 TI - Intraluminal thrombus in the cerebral circulation. PMID- 2911829 TI - Decline in US stroke mortality. Demographic trends and antihypertensive treatment. AB - Stroke mortality has been falling rapidly in this country since 1973. To investigate age-race-sex effects on stroke mortality, we studied US vital statistics during 1950-1972 and 1973-1981 in 55-64-, 65-74-, and 75-84-year-old race-sex groups. The accelerated rate of decline in stroke mortality since 1973 has had a substantial public health impact, with greater than 200,000 fewer stroke deaths than would otherwise have occurred. For all groups, stroke mortality declined at a greater rate (p less than 0.05) in 1973-1981 than during 1950-1972. The rates of decline during 1973-1981 were greater with increasing age (p less than 0.05) and were more substantial for younger blacks. There were no consistent differences in the rate of decline by sex. The greater rate of decline in absolute stroke mortality in the older age groups and blacks was explained by higher baseline mortality in these groups. Overall, stroke mortality decreased by approximately 2%/yr in 1950-1972 and by approximately 7%/yr after 1973. Rank order of average annual percent decline after 1973 by age-race-sex groups did not correspond to rates of change in treatment or control of hypertension obtained from three national surveys. The accelerated rate of decline after 1973 may have resulted from improved antihypertensive therapy, but our findings fail to confirm this hypothesis and suggest that treatment of hypertension may not be the principal reason for the decline in stroke mortality. PMID- 2911830 TI - Infrequency of blacks among patients having carotid endarterectomy. AB - We reviewed demographic data on patients having 2,256 carotid endarterectomies in eight large hospitals in North Carolina to determine the frequency of blacks among these patients. Blacks comprised only 4.6% of the patients having carotid endarterectomy even though they comprised 26% of all patients discharged and 22% of the general population of the state. Data from the National Inpatient Profile of the Commission on Professional and Hospital Activities, which represents patients discharged from short-term, nonfederal hospitals throughout the United States, show that nationwide, blacks comprise only 2.7% of the patients having carotid endarterectomy, whereas they comprise 12.0% of all patients discharged, 12.1% of the general population, and 10.7% of patients discharged following Class I surgical procedures. Blacks have only 67 carotid endarterectomies per 100,000 patients discharged; this rate is five or more times higher in whites. Among black patients having carotid endarterectomy, women predominate, whereas men predominate among white patients having carotid endarterectomy (p = 0.006). The underrepresentation of blacks among patients having carotid endarterectomy lends support to the concept that carotid vascular disease in blacks is distributed intracranially rather than extracranially as opposed to the extracranial rather than intracranial distribution in whites. PMID- 2911831 TI - Indium-111-labeled platelet scintigraphy in carotid atherosclerosis. AB - We evaluated platelet accumulation in carotid arteries by means of a dual radiotracer method, using indium-111-labeled platelets and technetium-99m-labeled human serum albumin, in 123 patients (92 men, 31 women; median age 60 years). Sixty patients had symptoms of transient ischemic carotid artery disease, and 63 patients with peripheral arterial occlusive disease served as controls. Antiplatelet treatment with acetylsalicylic acid was taken by 53 of the 123 patients. In 36 of the 60 symptomatic patients, platelet scintigraphy was repeated 3-4 days after carotid endarterectomy. Comparison of different scintigraphic parameters (platelet accumulation index and percent of the injected dose of labeled platelets at the carotid bifurcation) showed no significant differences between symptomatic and asymptomatic patients, and the severity of stenosis and the presence of plaque ulceration also had no influence on the parameters. There was no difference between patients with a short (less than 4 weeks) or long (greater than 4 weeks) interval from the last transient ischemic attack to scintigraphy and no difference between patients with or without antiplatelet treatment. Classifying the patients according to plaque morphology judged by high-resolution real-time ultrasonography also demonstrated no differences. No significant correlation was found between any scintigraphic parameter and other platelet function parameters such as platelet survival time, platelet turnover rate, and concentration of platelet-specific proteins. Quantification of platelet deposition after carotid endarterectomy in 36 patients demonstrated a significant increase of the median platelet accumulation index and the percent injected dose index. There were no significant differences between patients receiving high-dose (1.0 g/day) or low-dose (1.0 g/day) acetylsalicylic acid in scintigraphic results.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2911832 TI - Sex difference in antithrombotic effect of aspirin. AB - A number of clinical trials suggest that the antithrombotic effect of aspirin is limited to men. To test the possibility that this is due to a sex difference in the inhibitory effect of aspirin on platelet behavior, we studied whole-blood platelet aggregation in men and women and in male patients with carcinoma of the prostate receiving hormone therapy. The in vitro inhibitory effect of aspirin on so-called spontaneous platelet aggregation induced by stirring whole blood and monitored by the decrease in the number of singleton platelets was greater in men (mean +/- SD inhibitory ratio 1.54 +/- 0.30 in men, 1.23 +/- 0.22 in women; p less than 0.001). The inhibitory effect of aspirin was reduced in orchiectomized male patients and was restored by the addition of testosterone to blood samples. Estradiol had no detectable influence on the inhibitory effect of aspirin. Testosterone thus seems to influence platelet aggregation and its inhibition by aspirin as assessed by whole-blood in vitro aggregometry. Possible mechanisms for this effect of testosterone and its relevance to the choice of antithrombotic therapy are discussed. PMID- 2911833 TI - Whole blood platelet function in acute ischemic stroke. Importance of dense body secretion and effects of antithrombotic agents. AB - We studied platelet function in whole blood, a situation that better reflects the in vivo state, from 85 patients with acute ischemic stroke and from 19 healthy controls. Patients receiving no antithrombotic drugs demonstrated increased platelet dense body secretion without an associated increase in platelet aggregation, thus raising the possibility that dense body secretion may be of separate importance in cerebral infarction. Our results also suggest that dense body secretion may occur independently of aggregation. Heparin and heparin plus warfarin were ineffective in reducing the high level of dense body secretion seen in acute cerebral infarction, whereas treatment with aspirin plus dipyridamole inhibited both dense body secretion and platelet aggregation. It seems worthwhile to investigate the usefulness of antiplatelet drugs in the treatment of acute ischemic stroke wherein clinical outcome is correlated with the extent of suppression of platelet dense body secretion. PMID- 2911834 TI - Morbidity and mortality in the Systolic Hypertension in the Elderly Program (SHEP) pilot study. AB - The pilot study of the Systolic Hypertension in the Elderly Program was a randomized, double-blind, placebo-controlled trial of drug therapy for isolated systolic hypertension. It followed 551 elderly participants with untreated blood pressures of greater than 160/less than 90 mm Hg for an average of 34 months. Mean age of the participants was 72 years; 63% were women, and 82% were white. Pretreatment blood pressures averaged 172/75 mm Hg. Participants were randomly assigned to treatment with chlorthalidone or placebo as Step I medication. Blood pressures at annual visits averaged 141/68 and 157/73 mm Hg for the drug-treated and placebo-treated groups, respectively, with 60% and 33% of the survivors on blinded medication having systolic blood pressures of less than 160 mm Hg at their last annual visit. All-cause mortality rates for the drug-treated and placebo-treated groups were 25.4 and 22.7 deaths per 1,000 participant-years of risk, and rates for definite "first stroke" were 8.3 and 12.8 per 1,000 years of risk. Differences between groups were significant for systolic and diastolic blood pressure but not for death or stroke rates. A full-scale study has begun to determine the effects of drug therapy for isolated systolic hypertension on stroke and mortality rates. PMID- 2911835 TI - Blood velocity in the middle cerebral artery and regional cerebral blood flow during carotid endarterectomy. AB - Blood flow velocity in the middle cerebral artery, determined by transcranial Doppler ultrasonography, was monitored during 31 carotid endarterectomies. Electroencephalogram (EEG) was also monitored, and regional cerebral blood flow (rCBF) was measured. The relation between rCBF and mean velocity was dependent on the rCBF level; the correlation was strong if rCBF was less than 20 ml/100 g/min but weak if rCBF was greater than that level. Ipsilateral EEG suppression was related to a rCBF threshold of 9 ml/100 g/min and to a mean velocity threshold of 15 cm/sec; the rCBF threshold was more specific for EEG change. Postischemic hyperemia was evident in measurements of mean velocity but not of rCBF. These disparities between mean velocity and rCBF seemed to be due to three factors: 1) disproportionately high mean velocity in patients with stenosis of the middle cerebral artery, 2) a nonlinear relation between mean velocity and rCBF, and 3) the anatomically different regions of the brain in which mean velocity and rCBF are measured. The velocity measurement appeared to be relatively more sensitive than rCBF to hemodynamic events in the corpus striatum and internal capsule. PMID- 2911836 TI - Clinical and radiologic features of lacunar versus nonlacunar minor stroke. AB - We determined the angiographic presence of extracerebral and intracerebral arterial disease in 122 patients with minor stroke within the carotid territory; we excluded patients with a recognized cardiac source of emboli. Based on clinical features and computed tomographic findings, patients were classified as having lacunar infarcts (n = 61), nonlacunar infarcts (n = 53), and infarcts of indeterminate type (n = 8). Severe carotid bifurcation disease (greater than or equal to 50% stenosis or occlusion) was significantly more common in nonlacunar than in lacunar infarcts, on both the ipsilateral (p less than 0.001) and the contralateral (p less than 0.01) sides; 79% of the patients with nonlacunar infarcts had severe carotid bifurcation and/or middle cerebral artery disease on the ipsilateral side compared with 3.3% of the patients with lacunar infarcts. Our data underscore the need for classification of patients by the underlying mechanisms in future studies of treatment of ischemic stroke. PMID- 2911837 TI - Clustering of strokes in association with meteorologic factors in the Negev Desert of Israel: 1981-1983. AB - Clinical observations of the apparent clustering of daily stroke admissions to a regional hospital in an arid climate prompted our investigation of possible meteorologic factors associated with stroke admissions. Daily hospitalization and meteorologic data were studied for 895 patients with stroke admitted to Soroka Medical Center, Beer-Sheva, Israel, during 1981, 1982, and 1983. The average daily incidence of stroke was about twice as great on relatively warm days as on relatively cold ones. This increase may be explained by increases in thromboembolic mechanisms secondary to physiologic changes in response to heat. When heat waves are predicted, information on the added risk for stroke needs to be disseminated to both the population and to health care providers so preventive measures can be instituted. Special attention should be devoted to air conditioning and adequate consumption of liquids, and antiplatelet aggregation medication such as aspirin should be considered. PMID- 2911838 TI - Beneficial effect of nimodipine on metabolic and functional disturbances in rabbit hippocampus following complete cerebral ischemia. AB - We investigated the effects of intravenous application of nimodipine on the neurophysiologic, biochemical, and morphologic consequences of 15 minutes of global cerebral ischemia in seven rabbits. In vivo dialysis of the hippocampus was used to determine changes in extracellular concentrations of extracellular calcium and amino acids and blood-brain barrier permeability. Ischemia without treatment produced a rapid disappearance of electroencephalographic activity, a decrease in the concentration of extracellular calcium, the release of neuroactive amino acids, and leakage of methionine to the tissue fluid, plus a significant increase of the blood-brain barrier permeability to fluorescein. Except for permeability and electroencephalographic activity, these parameters normalized during 45 minutes of recirculation; permeability and activity failed to normalize completely during 3 hours of recirculation. After 3 hours of recirculation, morphologic changes in the CA1 hippocampal area were observed. Treatment with nimodipine significantly enhanced electroencephalographic activity recovery and normalization during recirculation, reduced the decrease in extracellular calcium concentration, and prevented the increased permeability of the blood-brain barrier. Nimodipine protected the CA1 area from early morphologic changes and reduced leakage of methionine from brain cells. The beneficial cytoprotective effect of nimodipine, probably related to normalization of calcium homeostasis and blood-brain barrier permeability after ischemia, may reflect both vascular and cellular sites of action. PMID- 2911839 TI - Nilvadipine attenuates ischemic degradation of gerbil brain cytoskeletal proteins. AB - We have previously demonstrated that transient cerebral ischemia induces marked decreases in concentrations of cytoskeletal proteins and have suggested putative involvement of calpain in the decrease of microtubule-associated protein 2 (MAP2) content. We examine the effect of nilvadipine, a new calcium channel blocker, on protein degradation in gerbil brains after 5 minutes of bilateral carotid artery occlusion and compare this effect with those of nimodipine and nicardipine. By densitometric quantification of the electrophoretically separated soluble proteins, mean +/- SEM MAP2 content in the hippocampus (14.4 +/- 1.8 micrograms/mg protein) was depleted (5.4 +/- 0.5 micrograms/mg, p less than 0.01) 4 days after ischemia; this depletion was significantly inhibited by 1 or 10 mg nilvadipine/kg/day. MAP2 content was also depleted in vitro when normal nonischemic brain extract was incubated with calcium, but this degradation was not inhibited by the calcium channel blockers. Our results suggest that calcium channel blockers do not act directly on calpain but act at the calcium channels of neurons and may suppress activation of the enzyme and attenuate ischemic degradation of cytoskeletal protein. We found nilvadipine to be the most potent drug among those studied, and we believe it could be useful for the treatment of cerebral ischemia. PMID- 2911840 TI - Focal ischemia enhances choline output and decreases acetylcholine output from rat cerebral cortex. AB - Choline concentration is rate limiting in the synthesis of acetylcholine. There is a negative arteriovenous difference for choline concentration across the brain, indicating the steady output of choline from this organ. Cerebral ischemia may increase extracellular choline concentration by interfering with its removal by the circulation and by enhancing its net production from phospholipids. We tested this hypothesis in six rats subjected to middle cerebral artery occlusion. We determined choline and acetylcholine output from the ischemic cerebral cortex by analyzing their concentrations in the fluid contained in cortical cups by gas chromatography-mass spectrometry. Mean +/- SEM choline output over 40 minutes before ischemia (baseline value) was 31.1 +/- 1.6 pmol/min/cm2. During ischemia, mean +/- SEM choline output rose to 100.8 +/- 13, 97.3 +/- 12.7, 100 +/- 22.4, and 93.1 +/- 16.9 pmol/min/cm2 in four consecutive 10-minute periods, respectively. Mean +/- SEM acetylcholine output was 15.6 +/- 1.1 before and 5.9 +/- 1.2, 8.3 +/- 2.6, 8.6 +/- 2.1, and 13.7 +/- 4.6 pmol/min/cm2 in the four 10 minute collection periods during ischemia. All four choline values and the first acetylcholine value during ischemia were significantly different from their respective baseline values. We conclude that ischemia induces an increase in extracellular choline concentration with possible implications for acetylcholine metabolism. The attending transient decline in acetylcholine output may be due to impaired release due to local hypoxia or to decreased acetylcholine synthesis. PMID- 2911841 TI - Tetramethylpyrazine for treatment of experimentally induced stroke in Mongolian gerbils. AB - Tetramethylpyrazine, a drug originally isolated from the rhizome of Ligusticum walliichi, has been used routinely in China for the treatment of stroke and angina pectoris. We evaluated this drug by testing its effectiveness in increasing the survival rate in a stroke model using Mongolian gerbils. Our results indicate that tetramethylpyrazine can increase survival rate only if it is administered before the induction of cerebral ischemia. Since we administered the drug intraperitoneally, it is possible that pretreatment was necessary to increase its effective concentration in the blood. Receptor binding studies indicated that tetramethylpyrazine was inactive against a variety of pharmacologically active receptors. PMID- 2911842 TI - Interaction between digoxin and propafenone. AB - The pharmacokinetic and pharmacodynamic interactions between digoxin and propafenone were investigated in 10 hospitalized patients with heart disease and cardiac arrhythmias. During steady state (0.25 mg/day) the glycoside was combined with 600 mg of propafenone daily for 1 week. The mean +/- SD serum digoxin concentration (SDC) was 0.97 +/- 0.29 ng/ml before and 1.54 +/- 0.65 ng/ml (p less than 0.003) during propafenone administration. Propafenone induced a mean decrease in 31.1 and 31.7% in total and renal digoxin clearances, respectively. The increase in SDCs was accompanied by a decrease in heart rate (HR) and shortening of QTC (QT interval corrected for HR). In patients receiving digoxin and propafenone simultaneously, the SDCs should be monitored and the digoxin dose reduced if there is evidence of toxicity. PMID- 2911843 TI - A rapid analysis of nafcillin using high-performance liquid chromatography. AB - A simple, rapid, and reproducible high-performance liquid chromatography method is described for the measurement of nafcillin using an internal standard (IS), 5 (p-hydroxyphenyl)-5-phenylhydantoin. A one-step protein precipitation was used for preparation of nafcillin and IS. The mobile phase included 0.02 M ammonium acetate buffered solution and acetonitrile (75:25 vol/vol). An Ultrasphere ODS reversed-phase column was used and the detector was set at 224 nm. The retention time of IS and nafcillin was 4.8 and 6.6 min, respectively. The absolute recovery for nafcillin ranged from 95-98%. The intraday coefficient of variation for the assay was 3.5% at nafcillin concentrations of 1.0 and 60 micrograms/ml. The interday coefficient of variation was 7.1 and 3.1% at the nafcillin concentrations of 1.0 and 60.0 micrograms/ml, respectively. The major advantages of this method include the single-step extraction and the use of a small volume (50 microliter) of serum samples for nafcillin measurement. The serum concentrations of nafcillin in a pediatric patient were determined to demonstrate the application of this method. PMID- 2911844 TI - Interpretation of excessive levels of inhaled tobramycin. PMID- 2911845 TI - A useful microscale method for monitoring furosemide by high-performance liquid chromatography? PMID- 2911846 TI - Interference of spironolactone metabolites in a digoxin radioimmunoassay. PMID- 2911847 TI - The need for a loading dose of gentamicin in neonates. AB - We studied pharmacokinetic variables in 100 neonates to evaluate the need for a loading dose of gentamicin. The mean volume of distribution for gentamicin in this population was .542 +/- .205 L/kg. Forty-five percent of these patients would not achieve peak serum concentrations of greater than or equal to 5 micrograms/ml after one dose of 2.5 mg/kg. A loading dose of 4 mg/kg would result in a level of greater than or equal to 5 micrograms/ml in 92% of the patients. After this study, a 4 mg/kg loading dose was initiated at our institution. Peak and trough concentrations at steady state were compared in 50 patients receiving a loading dose and 40 patients who had not received a loading dose. No significant differences were found in peak or trough concentrations after three or more doses, verifying that a loading dose does not affect steady-state concentrations. Because gentamicin toxicities are related to accumulation over time, whereas therapeutic efficacy may be related to early attainment of therapeutic peak serum concentrations, we recommend a loading dose of 4 mg/kg in all neonates beginning gentamicin therapy. PMID- 2911848 TI - Fluctuations of carbamazepine concentrations during the day for two slow-release preparations. AB - Fluctuations in the carbamazepine (CBZ) concentration during the day were studied using the profiles of 88 patients on slow release CBZ preparations. Blood was taken at 800, 1100, 1400, 1700, 2000, 2200 and 800 hr of the following day. The CBZ dosage was divided into two equal doses and administered at 800 and 2000 h. The influence of different factors on the fluctuations in the CBZ concentration during the day was studied. The fluctuation correlated negatively (r = -0.51, p less than 0.001) with the level-dose ratio LDR (CBZ morning concentration-CBZ dose per body weight ratio). The co-medication and preparation had no additional significant influence on fluctuations in the CBZ concentration during the day. The maximal CBZ serum concentration during the day can be described for most patients as a function of the CBZ morning concentration and the level-dose ratio using a suitable regression equation (r = 0.93, standard error of estimate = 1.2 mg/L). PMID- 2911849 TI - Prediction of individual dosage requirements for lignocaine: a validation study for Bayesian forecasting in Japanese patients. AB - The performance of the Bayesian feedback method for predicting lignocaine dosage developed by Vozeh et al. was evaluated in 53 Japanese patients, treated for either suppression or prophylaxis of ventricular arrhythmias, with respect to accuracy, precision, efficiency, and safety. The lignocaine serum concentrations at 12 h (C12) and 24 h (C24) after continuous infusion was started were predicted and compared retrospectively using the early concentration at 2-4 h (C2-4). The mean of the prediction error (PE) and the root mean-squared error (RMSE) were used as a measure of accuracy and precision. The 95% confidence interval of PE for C12 included zero, but those of PE for C24, whether C2-4 was used alone or in combination with C12, were less than zero, meaning that the prediction of C24 was significantly biased. The RMSE for C12 (13.2%) was less than that for C24 (16.2%), but the difference was not statistically significant. The fraction of measurements lying within the statistically approximate 68% prediction interval (+/- 1 SD) was used to evaluate the estimate of the SD of prediction. The fraction of measurements inside the prediction interval was significantly larger than the expected 68% for both C12 and C24 (p less than 0.05), showing that the estimate of the size of the PE is biased on the safer side. The clinical effects of lignocaine were also evaluated from the viewpoints of suppression of number of ventricular premature beats, prevention of more severe grades of arrhythmias, and toxicity. At least the appearance of toxicity, which four patients exhibited, was related to the lignocaine serum concentration (greater than 6 micrograms/ml). PMID- 2911850 TI - Clinical pharmacology of continuous infusion doxorubicin. AB - Fifteen patients were studied during short-term (5 days at 10-15 mg/m2/day) or long-term (5-104 days at 3 mg/m2/day) doxorubicin infusion. Levels of doxorubicin and metabolites in serum and 24-h timed urine collections were determined by high performance liquid chromatography. Quantifiable anthracycline levels were identified in serum of 5 of 6 patients (6 courses) receiving drug at 10 mg/m2/day. In 5 courses, total anthracycline levels were 10-80 ng/ml, whereas levels as high as 370 ng/ml were observed in a patient with hepatorenal failure. No detectable serum levels of anthracycline were seen in patients receiving long term doxorubicin therapy. Although analysis of 24-h timed urine collections revealed that doxorubicin was the predominant anthracycline, the extent of urinary elimination showed considerable interpatient variation (1.0-52.5% of the infused dose/24-h period on the short-term protocol and 5.3-57.2%/24-h period on the long-term protocol). Metabolic processing of doxorubicin administered by continuous infusion was found to be similar to that of drug given by bolus administration and showed no change in pattern with time. However, a greater variability in serum and urinary anthracycline levels was seen among patients on infusion schedules than has been noted with bolus drug treatment. PMID- 2911851 TI - The impact of a therapeutic drug monitoring program for phenytoin. AB - The current study was performed to document the cost savings and need for a therapeutic drug monitoring program for phenytoin. The methodology employed a prospective, randomized, crossover design that utilized two control and two therapeutic drug monitoring phases. The therapeutic drug monitoring program significantly decreased the average number of assays performed per patient from 2.14 to 0.61. Withdrawal of the program resulted in a significant increase in the average number of assays performed per patient (from 0.61 to 2.41), the average number of assays drawn incorrectly (from 0.39 to 1.89), and in the average number of assays used inappropriately (from 0.50 to 2.07). Withdrawal of the program was also associated with a significant increase in the average number of readmissions (from 0 to 0.19) within 3 months of discharge. Reinstitution of the program was associated with a significant decrease in the average number of readmissions (from 0.19 to 0.03) within 3 months of discharge. The cost savings from decreasing the number of assays performed was estimated to be $100.00 for the first year. PMID- 2911852 TI - Aminoglycoside dosing in pediatric patients. AB - We assessed the performance of a predictive algorithm for dosing aminoglycoside antibiotics in 75 pediatric patients and Bayesian feedback in 36. The absolute errors for peak and trough concentrations were 1.83 and 0.80 micrograms/ml, respectively, which seem clinically acceptable for most patients. However, the algorithm had significant negative bias for both peaks and troughs. Implementation of Bayesian feedback eliminated bias in a second set of concentrations and significantly decreased its magnitude for both peaks (p = 0.028) and troughs (p = 0.005). This method may allow more accurate dosing of aminoglycoside antibiotics in pediatric patients, though it would most likely be improved by better definition of population parameters and their variability. PMID- 2911853 TI - Comparison of aminoglycoside concentrations measured in plasma versus serum. AB - The terms "serum concentration" and "plasma concentration" are often used interchangeably in therapeutic drug monitoring, but few studies have addressed the comparability of serum and plasma drug concentrations. Before implementing a change in the procedure for measuring aminoglycoside concentrations in our institution, we prospectively compared values for tobramycin and gentamicin concentrations measured in serum and plasma. For the 208 samples that were tested, plasma aminoglycoside concentrations were significantly lower than those in serum. This relationship was similar for tobramycin and gentamicin, and was unaffected by the presence of concurrent therapy with ticarcillin. This difference, while statistically significant, was not, in our estimation, of sufficient magnitude to be of clinical importance. Plasma aminoglycoside concentrations may be considered equivalent to serum concentrations and, owing to the shorter processing time involved, appear to be the preferred medium for measuring these values. PMID- 2911854 TI - Erythromycin effects on multiple-dose carbamazepine kinetics. AB - To determine the effects of erythromycin on multiple-dose carbamazepine pharmacokinetics, seven healthy male volunteers were given 300-400 mg of carbamazepine each morning for 17 consecutive days. All subjects were given a placebo erythromycin form every 6 h on days 12, 13, and 14, then changed to erythromycin base 250 mg every 6 h for the final 3 days. Serial blood samples were drawn after the morning doses on days 14 and 17. Analysis of carbamazepine and carbamazepine-10,11-epoxide concentrations were made by high-performance liquid chromatography. Pharmacokinetic analysis showed carbamazepine half-life and 24-h postdose concentration to increase significantly (p less than 0.05) and oral clearance to decrease (p less than 0.05) during erythromycin administration. Decreases in carbamazepine-10,11-epoxide Cmax (p less than 0.001), area under the concentration-time curve0-24 (p less than 0.001), and carbamazepine-10,11-epoxide to carbamazepine ratio (p less than 0.01) also occurred during carbamazepine dosing. Erythromycin significantly inhibits the epoxide-diol metabolic pathway by which carbamazepine is transformed to carbamazepine-10,11-epoxide. Wide individual variability in this interaction should serve to warn practitioners of the unpredictability of this interaction. PMID- 2911855 TI - Isocratic separation of phenytoin metabolites by high-performance liquid chromatography from human and animal microsomes and urine. AB - A rapid and simple high-performance liquid chromatography analytical method is described for the quantitative determination of phenytoin and five of its metabolites--phenytoin dihydrodiol, catechol, methoxycatechol, para hydroxyphenytoin, and meta-hydroxyphenytoin--in biological materials. Following ethyl acetate extraction and incubation with beta-glucuronidase, samples were passed through a C18 Sep-Pak cartridge. The eluate was chromatographed on a reverse-phase 10 cm C18 Radial Nova-Pak (5 micron) column using a mobile phase of isopropanol:water (20:80) at a flow rate of 1.4 ml/min and monitored at 235 nm. Total chromatographic analysis time was 23 min, with complete baseline resolution of all metabolites. Five different columns and 10 different mobile phase conditions were studied to determine the best system. The 10-cm C18 Radial Nova Pak (5 micron) gave the best resolution, reproducibility, and durability. This method should prove applicable for clinical use as well as for research purposes. PMID- 2911856 TI - Improved liquid chromatographic fluorescence method for estimation of plasma sotalol concentrations. AB - This article reports a modified liquid chromatographic fluorescence assay that has proved in our laboratory to give robust performance for the purposes of therapeutic drug monitoring. The sample preparation involves extraction of alkalinized plasma into 1-pentanol/chloroform and back extraction into HCl. Acceptable reproducibility and accuracy data are presented over the concentration range normally encountered in patient samples. The detection limit (25 ng/ml) is approximately one-tenth the lowest calibration standard used in our laboratory for quantitating patient pre-dose specimens, making the method applicable to pharmacokinetic studies. PMID- 2911857 TI - High-performance liquid chromatographic determination of trimethoprim in serum. AB - A procedure for determining trimethoprim in serum is reported. It employs the same high-performance liquid chromatographic system described previously for measurement of anticonvulsants, barbiturates, theophylline, caffeine, acetaminophen, and chloramphenicol in serum. The sample preparation for trimethoprim is nearly identical. As a method extension, quantitation of serum trimethoprim on clinical specimens can be easily accommodated as required. PMID- 2911858 TI - Determination of caffeine in saliva by high-performance liquid chromatography: new sampling method for saliva using filter paper. AB - We report an assay method for the determination of salivary caffeine concentrations by high-performance liquid chromatography. A simple, new method for collecting mixed saliva using a piece of filter paper has been developed. An arbitrary amount of saliva is absorbed and a fixed amount of internal standard is added. The mean coefficient of variation of measurements repeated by changing both volumes absorbed and caffeine concentrations of saliva was 5.6% with this method. The detection limit was determined to be 0.5 microgram/ml. Precision of measurements and recoveries did not depend upon the volume of saliva absorbed. Four volunteers were given a capsule of 230 mg caffeine, and saliva was collected by the ordinary method using chemical stimulation with citric acid and by our filter paper absorption methods; the methods were compared. Salivary caffeine concentrations were always lower than plasma concentrations, and there were no big differences between two methods, although salivary concentrations measured by our method was higher, with a significant difference at 1.5 h after dosing. From the practical viewpoint this method would be convenient and sufficiently accurate. PMID- 2911859 TI - Establishment of a system to standardize acceptability criteria for alanine aminotransferase activity in donated blood. AB - A multilaboratory study was conducted to develop a system for standardizing alanine aminotransferase (ALT) acceptability criteria ("cutoffs") for donated blood. Without standardized cutoffs, each laboratory must develop its own cutoff, and this may not make optimal use of ALT testing to reduce transmission of non-A, non-B hepatitis (NANB). Defining an ALT acceptability criterion in absolute terms is necessary because relative cutoffs based on local donor populations may be affected by the prevalence of NANB in each community. This study involved 16 laboratories using 23 different analytic systems. The ALT results of the analysis of a plasma reference sample could be used to translate mathematically a single, absolute cutoff to units applicable to each analytic system. The distribution of ALT results in 1.4 million donations from across the country was established; basing the cutoff on this sample avoids the problems inherent in using a local donor base to establish a cutoff. We propose the implementation of a system to standardize ALT acceptability criteria to an activity level defined by analysis of a nationwide donor sample. PMID- 2911860 TI - Vancomycin-induced red cell aggregation. AB - Vancomycin, an antibiotic similar in structure to ristocetin, is used to treat staphylococcal infections. However, vancomycin-induced hemagglutination complicated red cell (RBC) serologic testing in the blood bank. At concentrations greater than 3.0 mg per ml, vancomycin caused spontaneous macroscopic red cell (RBC) aggregation; concentrations of 2.0 and 2.5 mg per ml were associated with weakly positive aggregation with anti-IgG and polyspecific antiglobulin reagents negative with anti-complement; and concentrations less than 1.5 mg per ml had no apparent effect. Ficin-treated RBCs demonstrated negative reactions with the antiglobulin reagents. Vancomycin-induced aggregation was reversed partially with 0.2 M trisodium citrate, and supernatant transfer studies showed that normal RBCs retained a significantly (p less than 0.025) greater percentage of vancomycin than did ficin-treated RBCs. Vancomycin causes the aggregation of RBCs, which can be a source of confusion in the blood bank. The mechanism(s) through which vancomycin enhances aggregation may be related to its polycationic properties and to its direct protein binding to the RBC membrane, although other nonimmunologic mechanisms may be operative. PMID- 2911861 TI - Mood states in the volunteer blood donor. AB - Mood changes across time were evaluated as they applied to the process of volunteer blood donation. Measures of mood (from the Mood Adjective Check List) were taken before and at three different intervals after blood donations by 245 college students. Anxiety scores were significantly higher before blood donation, and elation scores showed a significant increase following donation. Veteran donors experienced significantly less discomfort before donation. These findings imply that blood donations can be viewed as an "opponent-affective process," in which initial, mildly aversive feelings lead to positive aftereffects. Current findings suggest that blood donation can be explained, in part, by a self serving, addictive process. PMID- 2911862 TI - How should we test the tests? PMID- 2911863 TI - Paternity testing with an absent mother. The probability of exclusion of red cell surface antigen, Gm, Hp, and HLA systems in North American whites and blacks. AB - Blood tests in cases of disputed paternity can be extremely useful even when the mother's blood sample is not available. The mean probability of exclusion (A) of red cell surface antigen, Gm, Hp, and HLA systems was determined in this situation for North American whites and blacks by creating pairs of a man and an unrelated child. In whites, the most valuable of the systems investigated to indicate nonpaternity for false fathers were HLA, Rh, Fy, and MNSs, in that order. HLA, MNSs, and Gm were the most valuable systems in blacks. With all of the genetic systems used in this study, the combined probability of exclusion (CPE) of men falsely accused of paternity, in cases where the mother is absent, is approximately 95 percent for whites and 92 percent for blacks. Since only indirect exclusions are possible without the mother, the common test panel of HLA and red cell antigens may not always allow an adequate study. Extended testing is recommended to include additional genetic systems in order to achieve an average combined probability of exclusion of at least 95 percent. PMID- 2911864 TI - Bone marrow processing in the blood bank. PMID- 2911865 TI - An undetectable source of technical error that could lead to false negative results in enzyme linked immunosorbent assay of antibodies to HIV-1. AB - Since the institution of routine testing for antibodies to Human Immunodeficiency Virus (HIV) using the enzyme-linked immunosorbent assay (ELISA), the specificity and sensitivity of this assay system has received significant scrutiny. During previous use of this methodology, we have quantified rates of false biological positive results using commercial kit assays in a normal donor population. In this study, we have identified a potential source for false negative results. Using multiple lots of two different commercial ELISA kits, the absorbance readings at the test end point could not differentiate between normal non reactive donor samples and blanks containing no sample. These results occur using normal donor samples, even though the assays could distinguish between blank wells and the manufacturers' "normal controls", provided with the assay. Our findings suggest that a technical pipetting error is presently undetectable, either visually or by statistical methods, and could permit an untested, potentially HIV-1 positive, unit to be released into the transfusable blood supply. A possible solution is suggested. PMID- 2911866 TI - Risk factors of HIV-seropositive subjects detected through blood donation in France, 1985-1988. PMID- 2911867 TI - An unusual complication of FFP infusion: coagulation in the infusion set. PMID- 2911868 TI - Aluminum from glass vials contaminates albumin. PMID- 2911870 TI - Risk factors for sensitization by blood transfusions. Comparison of the UW/Madison and UC/San Francisco donor-specific transfusion experience. AB - We have tested the predictive model for risk of sensitization by donor-specific transfusions developed at the University of California, San Francisco for its applicability to the DST experience at UW/Madison. Patient sample sizes between the two groups were similar (n = 249 for UW/Madison, n = 261 for UCSF) and the two groups of patients had similar compositions in terms of mean age, ABO type, baseline panel-reactive antibody, and pregnancy rate. The two groups differed in that the UW/Madison group had a higher percentage of males, diabetic patients, previously transplanted patients, and 0 haplotype-matched (2 HLA-mismatched related and unrelated) recipients. In addition, all the UW/Madison patients received azathioprine (AZA) whereas only half the UCSF group was given AZA. Despite these differences, application of the UCSF model for prediction of sensitization by DST gave remarkably similar results in our patient population, with pregnancy, prior transplant, baseline PRA, and HLA antigen sharing giving similar odds ratios and P values. However, when female sex was included in the model along with the other variables, the significance of pregnancy risk disappeared. We have developed an alternative multivariate model using stepwise logistic regression that identifies baseline PRA greater than 40%, female sex, and prior transplant as significant risk factors for sensitization, while number of HLA (A, B, DR) antigens shared and increasing recipient age significantly decreased risk of sensitization by DST. PMID- 2911869 TI - Infection with human immunodeficiency virus in the Pittsburgh transplant population. A study of 583 donors and 1043 recipients, 1981-1986. AB - We performed a retrospective serologic survey of 583 organ donors and 1043 transplant recipients for antibodies to human immunodeficiency virus type 1 (HIV 1). Two (0.34%) of the 583 donors and 18 (1.7%) of the 1043 recipients had HIV-1 antibodies by enzyme immunoassay and by Western blot. Two of 5 seropositive recipients tested also had blood cultures positive for HIV-1. Seven (0.7%) of the 1043 transplant recipients had antibodies to HIV-1 before transplantation; 2 of these had hemophilia A, and 5 had previous transfusions. Eleven (1.3%) of 860 recipients followed for 45 days or more seroconverted to HIV-1 a mean of 96 days after transplantation. Likely sources of HIV-1 infection for 3 of these 11 recipients included a seropositive organ donor in 1 patient and high-risk blood donors in 2 patients. A definite source of HIV-1 infection was not found for the other 8 recipients, 3 of whom seroconverted to HIV-1 after institution of blood donor screening for HIV-1 antibodies. Seroconversion to HIV-1 was less common in kidney recipients than in liver, heart, or multiple-organ recipients (P less than 0.02). Nine (50%) of the 18 HIV-1 seropositive transplant recipients died a mean of 6 months after transplant surgery, and 9 (50%) are still alive a mean of 43 months after transplantation. AIDS-like illnesses occurred in 3 of the dead and 1 of the living patients and included pneumocystis pneumonia (3 cases), miliary tuberculosis (1 case), and recurrent cytomegalovirus infection (1 case). These data suggest that the course of HIV-1 infection is not more severe in transplant recipients receiving cyclosporine than in other hosts and that, despite screening of blood and organ donors, a small number of transplant recipients will become infected with HIV-1. PMID- 2911872 TI - Histocompatibility antigen expression by myocytes. PMID- 2911871 TI - Selective depletion of Kupffer cells in mice by intact ricin. PMID- 2911873 TI - Enhancement of thyroid allograft survival following organ culture. Alteration of tissue immunogenicity. AB - Hyperbaric oxygen (95%, O2, 25 psi, 48-hr culture) resulted in prolonged thyroid allograft (B10.A) survival in both primary and sensitized recipients (B10.AQR). Recipients receiving noncultured thyroid allografts uniformly rejected the graft by 35 days, while 100% of cultured grafts survived. Noncultured thyroid grafts transplanted to skin-graft-primed recipients were rejected by 21 days. In contrast, 86% of cultured grafts transplanted to primed recipients were still functioning at 35 days. Donor spleen cells or peritoneal exudate cells transferred at the time of thyroid transplant were unable to stimulate cultured allograft rejection. Allografts histologically examined 35 days after transplant revealed, in some grafts, focal cellular infiltrates adjacent to normal, uninfiltrated tissue. To determine if tissue modification was the mechanism of prolonged allograft survival, hyperbaric-oxygen-cultured thyroids were examined for MHC class I expression. Immunoperoxidase staining with monoclonal antibody to MHC class I molecules showed that cultured thyroids were unstained in contrast to fresh thyroids that were uniformly stained. Cytotoxic T lymphocytes specific for H-2Kk administered 10 days following thyroid transplant were unable to eliminate cultured grafts (80% survival) but completely destroyed noncultured grafts. These results indicate that hyperbaric oxygen culture altered MHC class I expression such that it was no longer detectable by monoclonal antibody or cytotoxic T lymphocytes. Thus, the mechanism, explaining graft prolongation after hyperbaric culture in addition to passenger cell depletion, may be alteration of graft antigenicity such that the graft is no longer perceived as foreign. PMID- 2911874 TI - Acceptance of murine thyroid allografts by pretreatment of anti-Ia antibody or anti-dendritic cell antibody in vitro. AB - A new method for thyroid allografts in mice was established. Thyroids of C67BL/6J mice were treated with collagenase, and the follicles were isolated using a Percoll density gradient technique. These follicles were treated with anti-Ia antibody (Ab) or anti-DC Ab plus complement in order to eliminate DCs. The follicles were then mixed with agarose and transplanted under the left renal capsule of BALB/c mice. One hundred days after transplantation, acceptance of the grafts was verified by both histological study and the incorporation of 125I into the grafts. Allografts treated with C were rejected, whereas allografts treated with Ab plus C were accepted. When nontreated thyroids of C57BL/6J mice were grafted under the right renal capsule of BALB/c mice that had accepted DC depleted thyroids of C57BL/6J mice, the nontreated thyroids were rejected. These findings indicate that DCs play a crucial role in the rejection of mouse thyroid allografts, and that the depletion of DCs permits allografts to be accepted without inducing donor-specific tolerance. Our method presented here may be developed as a viable strategy for the treatment of patients with congenital or acquired hypothyroidism. PMID- 2911875 TI - Graft-versus-host disease in fully allogeneic small bowel transplantation in the rat. AB - Small bowel and its mesentery contain considerable amounts of lymphoid tissue that can mediate graft-versus-host disease in small bowel transplant (SBT) recipients. Present studies determined the existence of GVHD in a fully allogeneic SBT model and examined the effect of donor pretreatment with ALS in eliminating GVHD. Adult male Lewis (Lew) rats received orthotopic small bowel transplants from untreated (LewxBN)F1 (LBNF1) donors (group 1) or Brown Norway (BN) donors that were untreated (group 2) or pretreated with ALS (days -2 and -1) (group 3). All recipients were treated with cyclosporine 15 mg/kg/day i.m. on days 0-6 postoperatively. Animals were weighed and examined daily for signs of rejection and GVHD. No animals in groups 1 or 3 showed any physical signs of GVHD, but all of those in group 2 had characteristic weight loss, diarrhea, and dermatitis between 4 and 6 weeks postoperatively, from which they all recovered. Histologic examination of skin and spleen at this time confirmed the presence of GVHD. The relative spleen weight [( spleen weight/body weight] x 100) of group 2 animals was also significantly greater than that of unoperated control Lew animals. Spleen cells obtained from group 2 animals at the time of subclinical GVHD, but not cells from group 1 or 3 animals, caused enlargement of popliteal lymph nodes when they were injected into the footpads of Lew rats. This study shows that GVHD can manifest itself in recipients of a fully allogeneic small bowel transplant even when rejection is prevented by effective immunosuppression with CsA. However, combined use of recipient treatment with CsA and pretreatment of donor animals with ALS eliminates all manifestations of GVHD. PMID- 2911876 TI - [Diagnosis and treatment of vesico-intestinal fistula]. AB - In a retrospective study of 28 patients with vesico-intestinal fistula, the maximal diagnostic latency was eight years. The most common causes were diverticulitis (16 patients) and carcinoma of the colon (4 patients). Recurrent urinary tract infections with pneumaturia and/or faecaluria were found in 23 patients. The diagnosis was most accurately confirmed by cystoscopy and barium enema which showed evidence of a fistula in 20 patients. Patients suffering from diverticulitis were managed with excellent results while surgical intervention in malignancy was associated with brief survival. Diverting colostomy as a sole procedure in patients with infravesical obstruction involves the risk of rectal miction. PMID- 2911877 TI - [Effect of posture on the diuretic treatment of decompensated cirrhosis and heart failure]. AB - The diuretic effect of the supine position was evaluated in six patients with cirrhosis and ascites and six with congestive cardiac failure. All patients received 1 mg bumethanide intravenously and were randomly assigned to either bed rest in the supine position or normal daily activity in the upright position for the next six hours. The diuretic response was similar in patients with heart failure and cirrhosis, and was significantly greater in the supine than in the upright position: mean 1,133 v 626 ml/6 h (p less than 0.01). The natriuresis was similarly greater during recumbency: mean sodium 96 v 45 mmol (mEq)/6 h (p less than 0.01), and the excreted potassium in six hours was similar in both postures. The glomerular filtration rate was 100 and 66 ml/min (p less than 0.01) and the heart rate 76 and 83 beats/min (p less than 0.05) in the supine and upright positions, respectively. Plasma concentrations of noradrenaline, renin, and aldosterone rose significantly during the upright position. The results suggest that the attenuated response to intravenous bumethanide in the upright position and during normal daily activity may be due to the activation of several, homoeostatic mechanisms which may reduce the excretion of water and salt. PMID- 2911878 TI - [Is earlier diagnosis of oral cancer possible?]. AB - Study of patients with oral carcinomas from the Finsen Institute in a five-year period, shows the survival to be significantly correlated to the tumour stage on referral. In order to improve the prognosis for these patients, earlier diagnosis and earlier referral for treatment to the oncological centre are necessary. PMID- 2911879 TI - [Long-term results of ileorectal anastomosis in the treatment of ulcerative colitis]. AB - During the period 1951 to 1987, ileorectal anastomosis in one or two seances, depending upon the activity of the disease, was carried out in 63 patients with ulcerative pancolitis. It is concluded that the operative procedure seen in relation to recent continence-retaining types of operation and despite the relatively great frequency of convertion of 20% will still constitute an alternative in surgical treatment of patients with ulcerative colitis. PMID- 2911880 TI - [CT in children with epilepsy. The value of cerebral CT in children with epilepsy]. AB - In a retrospective material of 66 children with epilepsy, computed tomographic scanning had been undertaken in 30 cases. Abnormal computed tomographic findings were observed in five children in the form of cerebral tumour or sequelae of head injuries or perinatal asphyxia. All five children had focal EEG changes but none of these as the only positive finding. The investigation had therapeutic consequences in one case only, viz the case where computed tomographic scanning confirmed the clinical suspicion of tumour. The value of computed tomographic scanning in children with epilepsy is discussed, particularly in children with focal EEG changes. PMID- 2911881 TI - [Whipple's resection in cancer of Vater's ampulla and the pancreatic head]. AB - A review is presented of 62 Whipple's resections between 1962 and 1984 for adenocarcinoma of the choledocho-duodenal junction (CDJ) and pancreatic head (PH). The operation was radical in 17 patients with CDJ (94%) and in 34 patients with PH cancer (77%). The cumulative 5-year survival rates were 22% and 9%, respectively. The overall perioperative mortality was 23%, but was lowered to 11% during the last five years. Histology, size of tumour and age also influenced survival. Sixteen of the 32 radically operated patients who survived more than three months had a period without pain. Whipple's resection is still the only hope for cure in otherwise fit patients with CDJ or PH cancer, estimated to be radically resectable by pre- and peroperative investigations. The operation should be centralized in a few departments. PMID- 2911882 TI - [Severe adverse effects of low-dose carbimazole treatment in hyperthyroidism. A retrospective study of 476 patients]. AB - A material of 476 hyperthyroid patients treated with carbimazole and 69 patients treated with PTU in the period from 1978 to 1986 were studied retrospectively. The antithyroid treatment was given in low dosage without supplementary thyroxine. The total frequency of adverse effects, defined as symptoms leading to discontinuance of the treatment, was 8.0% for carbimazole and 2.9% for PTU. There were no cases of agranulocytosis in the group treated with carbimazole, and one case in the group treated with PTU. No relationship between age and adverse effects could be demonstrated. The relationship between adverse effects and dosage is discussed, and it is concluded that low dosage treatment with carbimazole has a very low frequency of adverse effects in terms of agranulocytosis and toxic hepatitis. PMID- 2911883 TI - [The legislation concerning insight into medical records. A questionnaire study]. AB - A prospective questionnaire investigation including 105 patients was undertaken during the period 28.9.1987 to 15.11.1987 to investigate how much the patients knew and employed the legislation concerning insight into case records. PMID- 2911884 TI - [Aspiration pneumonia caused by an alternative drug]. AB - A case of aspiration pneumonia caused by an alternative drug in a 86-year old women is presented. Complications in the form of acute myocardial infarction with pulmonary oedema and left bundle branch block led to the death of the patient. PMID- 2911885 TI - [Pindborg tumor in the maxillary sinus. An unusual case of atypical facial pain]. AB - A woman aged 40 years had experienced left-sided facial pain for some months. Dental treatment did not result in any improvement. X-ray of the maxillary sinus revealed a tooth in the left maxillary sinus. At operation, this was shown to be a calcified epithelial odontogenic tumour (Pindborg tumour). PMID- 2911886 TI - [Crush accidents in mechanical revolving doors]. AB - During recent years, mechanical revolving doors have become commoner. A hitherto unnoticed traumatic mechanism resulted in a case of crushing endangering life in a revolving door of this type is presented. Prophylactic measures are suggested. PMID- 2911887 TI - [Generalized argyria due to the use of eyedrops containing silver nitrate]. AB - This paper describes a case of generalized argyria secondary to the excessive use of eye-drops containing silver nitrate. The diagnosis was confirmed by a skin biopsy showing deposits of metallic silver in the dermis. PMID- 2911888 TI - [Tension pneumoperitoneum]. AB - A case of tension pneumoperitoneum is presented. The importance of immediate intervention is emphasized. PMID- 2911889 TI - [Basic cancer biology]. PMID- 2911890 TI - [Ureteral stenosis following radiotherapy of uterine cervix cancer]. AB - Stricture of the ureter following irradiation therapy for cancer of the uterine cervix is observed in 0.2-2.8% of all patients. The incidence in the literature is reviewed. The etiology, anatomical localization, time of development and the diagnostic problems are discussed. Old and more recent methods of treatment are mentioned and two cases treated with JJ-catheters are reported. PMID- 2911891 TI - [Congenital laryngo-tracheo-esophageal cleft]. AB - A typical case of congenital laryngo-trachea-esophageal cleft (LTEC) is presented with a Review of the literature. LTEC is a rare congenital anomaly caused by defective fusion of the septum between larynx/trachea and hypopharynx/esophagus. The septum is formed by fusion of two lateral folds growing medially in very early foetal life. Fusion progresses in a cranial direction. Disturbances in septum formation result in LTEC. The disease gives respiratory problems with aspiration and excessive salivary production. The diagnosis is best made by intubating the larynx and examining the postcricoid region and anterior wall of the esophagus endoscopically. Stapling of the stomach, tracheostomy and secondary operative closure of the cleft has proved effective in the treatment of LTEC. PMID- 2911892 TI - [Obstruction of the larynx caused by an oncocytic papillary cystadenoma]. AB - A case of oncocytic papillary cystadenoma in the larynx in an elderly woman forms the basis for a discussion of the causes of, the symptoms and diagnosis of chronic obstructive conditions of the upper respiratory tract. PMID- 2911893 TI - [Late postoperative wound infection]. AB - In a retrospective study during the last ten years of postoperative wound infections, six cases of late infections were found with a maximum latency of 30 years. A combination of non-absorbable suture materials together with underlying disease seems to have initiated the late formation of wound abscesses. The use of non-absorbable suture seems to involve a life long risk of infection. PMID- 2911894 TI - [Sacrococcygeal teratoma]. AB - A rare case of sacrococcygeal teratoma in a newborn infant is reported. The clinical appearance is described, and the necessity of early detection and surgical removal of this potentially malignant tumour is emphasized. PMID- 2911895 TI - [Fish oil preparations]. PMID- 2911896 TI - [Gallbladder polyps in the normal population]. PMID- 2911897 TI - [AIDS epidemiology]. PMID- 2911898 TI - [Imipenem/cilastin (Tienam)]. PMID- 2911899 TI - [Cancer epidemiology in Denmark]. PMID- 2911900 TI - [Fish oils]. PMID- 2911901 TI - [Nocturnal erectile activity in erectile dysfunction. An examination of nocturnal penile tumescence and rigidity]. AB - The historical background for the use of sleep-related erections (nocturnal penile tumescence) to distinguish organogenic from psychogenic impotence is reviewed. A commercially available system for continuous, non-invasive measurement of penile tumescence and rigidity is presented. PMID- 2911902 TI - [Prognosis in severe alcoholic intoxication]. AB - Out of 489 patients admitted to the poisoning treatment centre in 1986, 122 had serum ethanol values of greater than or equal to 66 mmol/l (0.3 per cent). 55% of the patients were men and 45% women. 69.1% of this fraction was in the age range 30-49 years. Verbal contact could be achieved in 69.9%. 4.9% of the selected patients had systolic blood pressures of less than 90 mmHg. 0.8% had rectal temperatures of less than 36.5 degrees C. Aspiration of the gastric contents was performed in 63%. Tracheal tubes were inserted in 6.6% and three of the patients required ventilation. A woman of 36 years with a serum ethanol value of 0.32% died. 58.5% were alcohol addicts, among these 64% were males. 53% had psychiatric histories. The average stay was 1.0 days. Signs of serious poisoning were rare and therapeutic problems moderate. Contrary to what might be expected, no excess of non-abusers was found among the patients without verbal contact. The importance of close observation of persons with severe alcohol poisoning is emphasized. PMID- 2911903 TI - [Use of alternative forms of treatment by patients attending a pediatric outpatient clinic. A questionnaire study]. AB - A questionnaire investigation was sent to 402 patients attending a paediatric outpatient clinic. 94% replied. 31% had received alternative treatment. At the time of the investigation 8% were receiving treatment. In 70% of the children receiving alternative treatment, the reason for this treatment was identical with the diagnosis in the outpatient clinic. No sex differences were observed in seeking alternative treatment. The frequency was lowest for children aged 0-1 years (21%) and highest for children aged 6-7 years (42%). Fewest of the children came from social group V (25%) and the most numerous were from social group II (38%). 49% had paid less than 1,000 Danish crowns (approximately 80 pounds: -) and 9% had paid more than 2,000 Danish crowns (approximately 160 pounds: -) for the treatment. In 60% of the children, alternative treatment was sought on prompting from the family and friends. The commonest reasons for treatment were asthma/allergy (47%) and back/joint symptoms (11%). The commonest forms of treatment were osteopathy (50%), zone therapy (19%) and homeopathy (18%). 41% of the children receiving alternative treatment received orthodox medical treatment simultaneously. 77% of these continued the orthodox treatment prescribed by their practitioner unchanged. Thus, the patients thus sought manual and technical forms of therapy, frequently as a supplement rather than a genuine alternative to the treatment prescribed by the practitioner. PMID- 2911904 TI - [Acyclovir in the treatment of facial palsy due to zoster virus]. AB - The varicella zoster virus (VZV) is the cause of 7-10% of the cases of atraumatic facial palsy. In untreated cases, recovery is only partial. Out of five patients, treatment with acyclovir resulted in complete recovery after three weeks in four in whom treatment was commenced within three days of the onset of the palsy. In one patient in whom treatment was commenced more than four days after the onset of the palsy, only partial recovery had occurred after one year. PMID- 2911905 TI - [Brachial plexus injuries after catheterization of the internal jugular vein]. AB - During a period of 17 months, four cases of lesions to the brachial plexus after cannulation of the internal jugular vein were observed in the Department of Thoracic Surgery in Odense Hospital. Other possible complications are mentioned and a method of catheterization with the fewest possible complications is reviewed. Patients who have been submitted to catheterization of the internal jugular vein should be observed with particular attention to nerve lesions. These symptoms usually regress within a relatively short period. PMID- 2911907 TI - [Immersion in a bath despite a safety bath chair]. AB - A case of submersion is described. A mother left her child aged 8 1/2 months sitting in a "safety bath chair" in a full bath and found the child lying under the water shortly afterwards. The infant was hypotonic for a brief period but rapidly recovered without sequelae. Use of a "safety bath chair" gives a false sense of security and its use is warned against. PMID- 2911906 TI - [Alpine skiing--a hand injury despite safety hand grips]. AB - During a fall, a skier sustained two fractures of the metacarpal bones despite special safety hand grips on the ski-sticks. Altered design of these grips is recommended as a prophylactic measure. PMID- 2911908 TI - [Accidental strangulation in a perambulator--again]. AB - Three cases of accidental strangulation of children in prams are described. One of the cases has been described previously. The reason for the strangulation lies in the construction of the pram, so that the actual lower frame is collapsible, and when this occurs, the handle is folded over the collapsed frame. In the cases described, the security mechanisms were insufficient and the children were strangled between the handle and the bassinet. This construction is considered unsuitable and prams with different constructions are recommended. PMID- 2911909 TI - [Anterior dislocation of the shoulder caused by electric shock]. AB - Dislocation of the shoulder caused by electric shock is extremely rare and is frequently diagnosed late in the course of the condition. Late diagnosis and treatment make reduction difficult and increase the risks of permanent injuries. A case of unilateral anterior dislocation of the shoulder after a shock of 380 volts is presented here. The dislocation was diagnosed immediately and both reduction and recovery were uneventful. PMID- 2911910 TI - [Insects for human consumption]. PMID- 2911911 TI - [Diagnosis and treatment in general practice. I. The course of illness in primary health service]. AB - The purpose of this review is to present an outline of the use of the unifying concepts of "episodes of medical care" and "episodes of illness" in recent research. The review focuses on theoretical and methodical problems connected with the use of these concepts in research related to general practice. The concept of "episodes of medical care" has been accepted as a valid and useful method of clustering discrete units of services into cohesive entities in previous literature. The concept of "episodes of illness" is, on the other hand, not yet fully defined and further development of this concept is suggested in the paper. The major methodical problem in connection with the use of these concepts is how to define when an episode starts and ends. Three typical examples on how research workers have dealt with this problem are presented and the consequences their choice of definitions have on the results from such studies are outlined. The concept of "episodes of medical care" has hitherto been used mostly in various utilization and morbidity studies in the primary health care sector and psychiatry. In the last decade the concept has also been used especially in American research in connection with studies focussing on the performance of medical care systems. The concept of "episodes of illness" has only been used in connection with relatively few population studies. PMID- 2911912 TI - [Diagnosis and treatment in general practice. 2. Episodes of medical care of health problems during a period of 3 months]. AB - The object of this article is to describe the working process in general practice. One hundred general practices were selected at random in the County of Copenhagen. Fifty-five general practices participated and registered the contacts during the period 13.9.1982 and the next three months for a random sample of group I patients from the low income group of the Danish Health Insurance and born on the 13th of a month. Where each contact is concerned, the individual health problems were registered together with the form of contact, the reason for contact, the wishes of the patient and the doctor's actions and also the diagnosis. Thirty-six % of the low income insurance group men and 37% of the women had at least one contact with general practice in the course of the three month period. Seventy-nine episodes of medical care per 100 persons were found in a period of investigation of three months and women had nearly twice as many episodes of medical care as the men. In 59% of the episodes of medical care, the patients had at least one symptom. In 22% of the episodes of medical care, the patients were referred to other persons or instances. In 73% of the episodes of medical care, the general practitioner established the final diagnosis. PMID- 2911913 TI - [Diagnosis and treatment in general practice. 3. Reasons for contact and diagnoses in episodes of medical care]. AB - The object of this article is to describe the reasons for contact and the diagnoses in general practice by following the course of health problems in a random sample of patients (group 1 in the National Health Insurance System) for three months. In 55 general practices in the County of Copenhagen, all contacts concerning a given health problem in the single individuals were registered. This totalled 1,974 episodes of medical care in approximately 1,200 persons who formed 47% of the random sample. This investigation assessed the various classifications of reasons for encounter with primary health care as regards employability for central coding, information value and agreement with the general medical disease model. Employing the Reason for Visit Classification (USA) supplemented by classifications elaborated by the authors, three dimensions of the concept of "reasons for encounter" could be described: symptoms, the patient's wishes for contact with the doctor and reasons for the current problem. Health problems are described as episodes of one or more contacts. In single-contact episodes, the symptoms and diagnoses are most frequently those of respiratory diseases whereas multi-contact episodes are most frequently found where musculo-skeletal diseases are concerned. It is concluded that a multi-dimensional description of the reasons for contact and a description of the disease pattern on the basis of episodes of medical care can provide more differentiated knowledge about health problems in general practice. PMID- 2911914 TI - [Diagnosis and treatment in general practice. 4. General practitioners' knowledge of their patients]. AB - The object of this work is to describe aspects of general practitioners' knowledge of their patients and to analyse the connection between this knowledge and certain activities involving the patients in the practice (examination in the practice, prescription of medicine, information and referral). Fifty-five practices with a clientele of 81,600 patients in the lower income group of the Danish National Health Insurance over the age of 15 years participated. A random sample of 1/30 of the insured persons were characterized by the practice prior to a period of observation of three months on the basis of the doctors' knowledge of the persons. During the period of observation, all practice-patient contacts were registered. The characteristics of the patients included: curation of attachment to the practice, degree of knowledge, previous problems etc. Contact data included information about diagnoses, symptoms, patient's wishes, prescriptions, referrals, information given and examinations in the practice. During the three months, a total of 1,974 episodes of medical care occurred. We did not find any connection between the duration of knowledge (as a measure of knowledge) and the number of abovementioned activities in the practice. This investigation, however, cannot exclude such a connection. Information is still required to illustrate the significance of the knowledge of the patients for the solution of their problems and, in particular, for the course of their health problems. PMID- 2911915 TI - [Diagnosis and treatment in general practice. 6. Attitudes of general practitioners--a study in Copenhagen County]. AB - We assume that general practitioners' (GPs) attitudes have considerable significance for their daily work, partly because the "free enterprise" structure permits GPs a fair degree of work autonomy, partly because several studies point to notable variations in GP behaviour which have not been explained by other variables. General practitioners seem to have developed an official professional ideology which differs in some respects from the ideology of other doctors. The core issues of Danish GP ideology, according to commission reports, textbooks and research can be summarized into four main principles: 1. A holistic (bio-psycho social) model of disease, 2. The GP as a family doctor, 3. The GP as a "gate keeper" (the central referral role) and 4. General practice as a "free enterprise". We mailed attitude questionnaires to a random sample of 100 practices in the county of Copenhagen. The purpose of the study was to establish the extent to which GPs would agree to the above ideology, and also to look for systematic differences between groups of doctors. The response rate was 76%. We found overall agreement to the family doctor principle among GPs which is in accordance with earlier studies. Attitudes to the "free enterprise" principle of practice organization were favorable in a similarly homogeneous way, and a significant minority favored even further liberalization. Disagreements were more pronounced concerning the holistic (bio-psychosocial) model of disease. Just over half of respondents adhered fully to the model, but doctors from high-income areas were significantly less enthusiastic than other doctors about the model. Similarly, most general practitioners favored the "gate-keeper" role.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2911916 TI - [Familial isolated thrombocytopenia. A family with autosomal dominant heredity]. AB - Thrombocytopenia as a hereditary isolated phenomenon is recognized in an X-linked recessive form and also an autosomally dominant form. Investigation of a family with the autosomally dominant form is presented. This condition is important in the differential diagnosis in cases of suspected immune thrombocytopenia as the autosomally dominant form does not respond to splenectomy. PMID- 2911917 TI - [Severe toxic hepatitis during flutamide (Eulexin) treatment]. AB - A case of severe toxic hepatitis in a patient with metastatic prostatic cancer treated for three months with flutamide (Eulexin) combined with an LHRH analogue, goserelin (Zoladex) is described. The patient developed severe liver failure with jaundice, ascites and severe encephalopathy. The condition reversed after discontinuation of flutamide. Less severe, but otherwise similar, adverse reactions have been reported in the literature, and the importance of considering the drug as a potential hepatotoxin is stressed. PMID- 2911918 TI - [Serious risk of anesthetic systems built over a Hafnia-D-system or a 3-way scuttle. Erroneous assembling of anesthetic systems might cause fatal pulmonary damage]. PMID- 2911919 TI - [Muscular dystrophy and exercise--benefit of harm?]. PMID- 2911920 TI - [Confusio congenialis epidemica]. PMID- 2911921 TI - [Physicians should not only treat patients. They should sell health]. PMID- 2911922 TI - Mortality in prostatic carcinoma. AB - One hundred forty-seven patients definitively irradiated for biopsy-proved adenocarcinoma of the prostate from December, 1975, to March, 1979, have either died after a median survival of forty-five months or have been followed up for a minimum of seven years. Seventy-six patients (52%) are currently alive, 62 of them with no evidence of disease. Seventy-one patients (48%) have died, 28 without disease. In addition, 12 patients died with prostatic carcinoma but of other causes. In assessing the characteristics of those patients who remain disease-free following treatment, a significant difference in disease control was seen based on tumor stage, histologic differentiation, pelvic lymph node status, and whether or not tumor was present microscopically at rebiopsy. Of those deceased patients with recurrent prostate cancer, more than one-half had distant metastasis only. In all, 61 percent of patients had no further evidence of prostatic carcinoma after definitive irradiation, 20 percent had distant metastasis alone, and only 18 percent had locally recurrent disease along with distant disease spread. PMID- 2911923 TI - Use of prostaglandin E1 for papaverine-failed erections. AB - The use of prostaglandin E1 is introduced as a pharmacologic agent that can produce artificial erections in patients who have failed the initial papaverine test or who were on self-injection programs and later lost rigidity. PMID- 2911924 TI - Penile prosthesis surgery: review of ten-year experience and examination of reoperations. AB - Our ten-year experience from September, 1975, to December, 1985, with 417 penile prostheses in 290 patients is presented. Arteriosclerosis and diabetes mellitus were the two most common causes of impotence in our patient population. The Scott inflatable penile prosthesis accounted for the majority of all implants and all device failures. Complications leading to device failure and/or reoperation occurred in 36 percent of all prostheses. However, including repairs, 91 percent of patients were left with a functional prosthesis. Examination of reoperated patients showed an average increase in corporeal length of 1.67 cm with repeat prosthesis operations (p less than 0.001). No increase in incidence of prosthesis failure could be shown after multiple reoperations. PMID- 2911925 TI - Use of retrograde lavage catheter during ESWL treatments. AB - Use of a retrograde lavage catheter utilizing a Water-Pik for the removal of stone fragments during an extracorporeal shock-wave lithotripsy (ESWL) treatment is described. Three of 4 patients treated to date have been essentially stone free at the end of their ESWL treatment. Urinary extravasation and ureteral stricturing have not occurred. PMID- 2911926 TI - Role of epididymis in sperm maturation. AB - One hundred ninety patients with obstructive azoospermia caused by bilateral epididymal blockage have been followed up for four years or longer after undergoing "specific tubule" vasoepididymostomy. When anastomosis was required in the corpus epididymis, the "patency" rate was 78 percent, and the overall pregnancy rate was 56 percent. The pregnancy rate for "patent" cases was 72 percent, indicating that a high fertility rate can be obtained with sperm that have not transited the full length of corpus epididymis. By contrast, with vasoepididymostomy to the caput epididymis there was a 73 percent "patency" rate, but the overall pregnancy rate was only 31 percent. The pregnancy rate for "patent" cases was 43 percent. Sperm from the corpus epididymis have a higher rate of fertility than sperm from the caput epididymis, but sperm from proximal areas of the corpus have no less fertility than sperm from the distal corpus epididymis. The most remarkable observation is that in almost half the cases sperm that have never journeyed beyond the caput epididymis seem to be capable of causing pregnancy. PMID- 2911928 TI - Giant vesical calculus formed around arterial graft incorporated into bladder. AB - A case is described of a giant vesical calculus formed around an arterial graft incorporated into the bladder. Awareness that a variety of foreign bodies may serve as a nidus for a calculus is necessary to prevent catastrophic consequences. PMID- 2911927 TI - Invasive adenocarcinoma of bladder response to cisplatinum, methotrexate, and vinblastine chemotherapy. AB - Primary invasive adenocarcinoma of the bladder was diagnosed in a fifty-two-year old male with a two-month history of irritative voiding symptoms. He was treated with three courses of cisplatinum, methotrexate, and vinblastine with marked regression of tumor shown radiographically and cystoscopically. Subsequent prostatocystectomy and ileal loop diversion revealed invasive tumor through the bladder wall to regional lymph nodes. The patient had two postoperative courses of the same chemotherapeutic regimen and is without evidence of disease recurrence at one year. PMID- 2911929 TI - Late appearance of perineal implantation of prostatic carcinoma after perineal needle biopsy. AB - A case is reported of a patient with carcinoma of the prostate and perineal tumor implant five years after perineal needle biopsy. This is the second case of the rare complication in which the implant appeared years after the biopsy. He was treated with wide excision of the tumor. PMID- 2911930 TI - Tissue expansion of underdeveloped scrotum to accommodate large testicular prosthesis. A technique. AB - A contracted empty scrotum in a young man will not accept an artificial testis satisfactorily using any of the standard techniques. Previous operative scars, as from a failed orchiopexy, have often added to the difficulties. Greatly enlarging the scrotum by gradual distention of a tissue expander implanted in the contracted side has been successful in overcoming this problem, both cosmetically and functionally. PMID- 2911931 TI - Single fill bladder evacuation. PMID- 2911932 TI - Magnetic extraction of intravesical foreign body. PMID- 2911933 TI - Post-traumatic unilateral hydronephrosis with hypertension treated by embolization. AB - A case of post-traumatic renal hypertension secondary to unilateral hydronephrosis is presented. The patient was treated with embolization of the renal artery and remains normotensive two years after the procedure. PMID- 2911934 TI - Urologic aspects of tethered cord. AB - Tethered cord syndrome, a form of spinal dysrhaphism, may involve vesical neurologic dysfunction. We present herein 60 cases of tethered cord syndrome, including 24 patients who underwent preoperative urodynamics studies. Preoperative cystometrography revealed areflexic bladders in 71 percent of cases and hyperreflexic bladders in 29 percent. Eight patients had serial pre- and postoperative urodynamics testing. Slight improvement was noted in postoperative urodynamics studies performed on 4 of 6 areflexic bladders and in the only hyperreflexic bladder studied. In addition, of the 3 patients in the serial urodynamics groups who had urinary symptoms preoperatively, 2 noted clinical improvement postoperatively. The urologist's role is important in the early detection, evaluation, and treatment of tethered cord syndrome and the neuropathic bladders that may result. PMID- 2911935 TI - Nosocomial urinary tract infection. PMID- 2911936 TI - Urethral profilometry in Scott artificial urinary sphincter. PMID- 2911938 TI - Comparison of maternal to fetal transfer of 3,5,3'-triiodothyronine versus thyroxine in rats, as assessed from 3,5,3'-triiodothyronine levels in fetal tissues. AB - Thyroxine (T4) is transferred from the mother to the hypothyroid rat fetus late in gestation, mitigating T4 and T3 deficiency in fetal tissues, the brain included. We have now compared the effects of maternal infusion with T3. Normal and thyroidectomized rats were started on methimazole (MMI) on the 14th day of gestation, given alone, or together with a constant infusion of 0.45 micrograms (0.69 nmol) T3 or of 1.8 microgram (2.3 nmol) T4/100 g per day. Maternal and fetal samples were obtained at the 21st day of gestation. The doses of T3 and T4 were biologically equivalent for the dams, as assessed from maternal plasma and tissue T3, and plasma TSH levels. MMI blocked the fetal thyroid; T4 and T3 levels were low in all fetal tissues, and fetal plasma TSH was high. Maternal infusion with T4 mitigated both T4 and T3 deficiency in all fetal tissues, the brain included, and decreased fetal plasma TSH. In contrast, infusion of T3 normalized fetal plasma T3 and increased the T3 levels in several tissues, but not in the brain. Neither did it decrease the high fetal plasma TSH levels. The results show that when the fetus is hypothyroid, T3 crosses the rat placenta at the end of gestation, but does not affect all tissues to the same degree. In contrast to the effects of maternal T4, maternal T3 does not alleviate the T3 deficiency of the brain or, presumably, of the thyrotrope. Thus, end-points of thyroid hormone action related to TSH release should not be used to measure transfer of maternal T3 to the fetal compartment. Moreover, T4 should be given, and not T3 to protect the hypothyroid fetal brain. PMID- 2911937 TI - Effects of repetitive administration of growth hormone-releasing hormone on growth hormone secretion, insulin-like growth factor I, and bone metabolism in postmenopausal women. AB - This study sought to determine whether GH response to synthetic GHRH was impaired in 13 postmenopausal (55-71 years) as compared with that in 8 eugonadal women and whether IGF-I and bone metabolism were consequently depressed. Thereafter, the effects of daily iv injections of 80-micrograms GHRH-44 for 8 days were studied in the same postmenopausal group. In addition to significantly higher basal IGF-I and osteocalcin levels (P less than 0.005) in eugonadal as compared with the postmenopausal women, the administration of one GHRH-44 injection resulted in significantly higher 120-min postinjection GH maximum peak and cumulative responses in the former group as well (P less than 0.005). Highly significant correlations were observed between 17 beta-estradiol plasma levels and either GH maximum peak or cumulative responses to GHRH-44 when both groups were pooled together, but not when considered independently. In postmenopausal women, a correlation was found between both age and duration of menopause and GH responses. Repeated GHRH-44 injections in postmenopausal women induced a significant increase in GH response (P less than 0.001) as well as in IGF-I levels from day 4 to 8. No phospho-calcium parameters were modified except for a significant rise in osteocalcin from day 2 to 8. These data indicate an age related loss of sensitivity of somatotrope cells to GHRH-44 in postmenopausal women, partly corrected by repeated daily GHRH-44 injections. As a consequence of the GHRH-induced increase in GH secretion, IGF-I was also enhanced and may be responsible for a stimulatory effect on bone formation, as shown by the osteocalcin increase, uncoupled from bone resorption. PMID- 2911939 TI - Growth hormone (GH) responsiveness to GHRH in normal adults is not affected by short-term gonadal blockade. AB - The effects of changes in circulating gonadal steroids on GH secretion elicited by GHRH challenge (1 microgram/kg) in normal adults volunteers (aged 18-24 years), were evaluated in 10 women and 10 men before and after gonadal blockade was achieved by a GnRH agonist (1500 micrograms/day by nasal spray for 40 days). To see if the effect of testosterone on GH secretion was dependent on its aromatization to estradiol (E2), GHRH tests were performed in 7 normal men prior to administration of testosterone enanthate (250 mg im), 8 days after this treatment had began, and again after E2 receptor blockade with tamoxifen (30 mg for 2 days plus 10 mg on the third day 2 h before the GHRH test, po) administered 8 days after testosterone enanthate. The study of the functional status of the somatotropes at the time of GHRH testing was made according to our previous postulate. Short-term gonadal blockade did not affect the parameters of GH response to GHRH in neither women nor men. Thus, the functional blockade of the gonads may be advisable as an adjunct therapy in the treatment of hypothalamic GH deficiency during the peripubertal stage. In the other group of men, administration of testosterone enanthate significantly increased GHRH-elicited GH release, but this was reverted after E2 receptor blockade. Since the hypothalamic somatotrope rhythm was altered by both these pharmacological manipulations, it appears that testosterone acts on GH release mainly at the suprapituitary level, and that this action is secondary to its aromatization to E2. PMID- 2911940 TI - Naloxone affects the release of cortisol, but not of vasopressin or oxytocin, in dehydrated sheep. AB - Ovariectomized ewes (N = 7) were dehydrated for 24 h and then given iv injections of saline vehicle or 8 or 64 mg naloxone hydrochloride in saline. Blood samples were taken by jugular venepuncture before and after dehydration and at intervals during the 90 min period directly following naloxone treatment. Plasma concentrations of AVP, OT and cortisol were measured by radioimmunoassay. Plasma AVP levels and osmolality increased with dehydration, OT concentrations showed no consistent change, and cortisol levels were unaffected. After administration of naloxone, AVP and OT concentrations did not alter. The sampling procedure increased plasma cortisol levels and the duration of this response was prolonged by the 64 mg dose of naloxone. PMID- 2911941 TI - A correlative study between glucocorticoid receptor levels in human mononuclear leukocytes and biochemical data in Cushing's disease. AB - We determined glucocorticoid receptors in human mononuclear leukocytes in 9 patients with Cushing's disease, in order to correlate them with laboratory data. Receptors were measured by a whole-cell assay method, after incubation with [3H] dexamethasone in the presence or absence of excess unlabelled hormone. In Cushing's disease, there were 4425 +/- 364 sites/cell (N = 9), similar to in the controls: 4473 +/- 476 (N = 10); average Kd was 2.42 +/- 0.52 nmol/l (N = 3) similar to in the controls: 2.0 +/- 0.20 nmol/l (N = 3). In Cushing's patients we found significant negative correlations between basal glucocorticoid receptors and: 1) morning blood cortisol (r = -0.67, P less than 0.05), and 2) 17-ketogenic steroids after 2 mg of dexamethasone (r = -0.85, P less than 0.01). No correlations were observed with afternoon blood cortisol, free urinary cortisol, basal and post-8-mg dexamethasone 17-ketogenic steroids, TRH-TSH area, urinary calcium, plasma glucose, or systolic blood pressure. CONCLUSIONS: In Cushing's disease, a subtle receptor down-regulation may exist, as suggested by the inverse relationship between glucocorticoid receptors and morning blood cortisol. Secondly, the relationship between basal receptors and 17-ketogenic steroids after 2 mg of dexamethasone suggests that glucocorticoid receptors in human mononuclear leukocytes could reflect the sensitivity of the nervous system pituitary-adrenal axis to dexamethasone inhibition. PMID- 2911942 TI - Properties of 5'-deiodinase of 3,3',5'-triiodothyronine in rat skeletal muscle. AB - To characterize rT3 5'-deiodinase (5'D) in rat skeletal muscle, the effects of altered thyroid status and PTU on rT3 5'D were studied. rT3 5'D activity was measured by incubating homogenates of rat skeletal muscle with [125]rT3, iodine labelled in the outer ring, in the presence of 20 mmol/l DL-dithiothreitol. This activity was observed to increase significantly 24 h after a single sc injection of T3 (75 micrograms/kg). The increase following the daily administration of this drug (15 or 75 micrograms/kg) for 3 and 14 days was dependent on the dose and number of previous days of injection. A significant decrease in activity was observed 2 weeks after thyroidectomy. The addition of 0.1 mmol/l 6-n-propyl-2 thiouracil (PTU) to the incubation medium in vitro caused a marked reduction in the activity in homogenates of skeletal muscle from hypothyroid, euthyroid and hyperthyroid rats. PTU, present at 0.05% in the drinking water for 2 weeks virtually abolished it. The properties of rT3 5'D in rat skeletal muscle thus appear to be essentially the same as those of type I enzyme with respect to response toward altered thyroid status and PTU. PMID- 2911943 TI - The metabolic clearance rate, serum half-time and apparent distribution space of authentic biosynthetic human growth hormone in growth hormone-deficient patients. AB - We studied the metabolic clearance rate (MCR) serum half-time (t1/2) and apparent distribution space (DS) of unlabelled, authentic, biosynthetic human growth hormone (B-hGH) in 9 GH-deficient patients by means of the constant iv infusion to equilibrium technique. B-hGH was infused for 3 h at a rate of 33 ng.kg-1.min-1 after which the disappearance from serum of GH was followed for 1 h. The mean +/- SEM values for MCR, t1/2 and DS were: 2.3 +/- 0.6 ml.kg-1.min-1, 21.1 +/- 1.7 min and 67.6 +/- 14.6 ml/kg, respectively. The disappearance of GH was monoexponential for the first 30 min, during which 75% of the GH had been cleared. The disappearance rate during the last 30 min of the observation period was somewhat lower, still approximately 90% of the GH had been eliminated after 60 min. PMID- 2911944 TI - Adult education strategies important for nurses. PMID- 2911945 TI - Mother-preterm infant relationships in the NICU. PMID- 2911946 TI - What nurses are saying about nursing. Part One. PMID- 2911947 TI - Addiction among nurses: facing the issue. PMID- 2911948 TI - Sympathetic vascular control of the pig nasal mucosa (III): Co-release of noradrenaline and neuropeptide Y. AB - The overflows of noradrenaline (NA) and neuropeptide Y like immunoreactivity (NPY LI) and vascular responses upon sympathetic nerve stimulation were analysed in the nasal mucosa of pentobarbital anaesthetized pigs. In controls, a frequency dependent increase in NA overflow was observed whereas detectable release of NPY LI occurred only at 6.9 Hz. Parallel decreases in blood flow in the sphenopalatine artery and vein and in nasal mucosa volume (reflecting blood volume in the venous sinusoids) were observed. The laser Doppler flowmeter signal (reflecting superficial blood flow) increased upon low and decreased upon high frequency stimulation. Twenty-four hours after reserpine pretreatment and preganglionic decentralization, the NA overflow was abolished while a frequency dependent release of NPY-LI occurred. Forty, 60 and 80% of the vasoconstrictor responses then remained upon stimulation with a single impulse, 0.59 and 6.9 Hz, respectively. Both the vasoconstriction and NPY-LI overflow, however, were subjected to fatigue upon repeated stimulation. In reserpinized animals release of NPY-LI and vasoconstrictor responses were larger upon stimulation with irregular bursts at 0.59 Hz compared to effects seen at stimulation with continuous impulses. Pre-treatment with the alpha-adrenoceptor antagonist phenoxybenzamine or the monoamine reuptake inhibitor, desipramine, enhanced NA overflow by 2-3 and 1.5 times at 0.59 and 6.9 Hz, respectively. Phenoxybenzamine significantly reduced the nerve-evoked vascular responses while the release of NPY-LI at 6.9 Hz was increased. Desipramine increased the functional responses but reduced the NPY-LI overflow. During tachyphylaxis to the vasoconstrictor effects of the stable adenosine 5'-triphosphate (ATP) analogue alpha-beta methylene ATP (mATP) in controls, the vasoconstrictor responses as well as the NA and NPY-LI overflow to nerve stimulation were unmodified. In reserpinized animals, however, the vascular responses and the overflow of NPY-LI were reduced after mATP tachyphylaxis. These data show that both NA and NPY are released upon sympathetic nerve stimulation in the nasal mucosa in vivo and this release seems to be regulated via prejunctional alpha-adrenoceptors. The lack of effect of mATP tachyphylaxis under control conditions makes it less likely that ATP serves as a major mediator of the large nonadrenergic vasoconstrictor component. PMID- 2911949 TI - Vagally mediated vasodilatation by motor and sensory nerves in the tracheal and bronchial circulation of the pig. AB - A new in vivo model is described in which anaesthetized pigs were used to study vascular responses in the bronchial, upper tracheal and laryngeal circulation upon electrical stimulation of the vagal or superior laryngeal nerves. Vagal or superior laryngeal nerve stimulation increased blood flow in the bronchial artery and the superior laryngeal artery, respectively. After pre-treatment with atropine the vasodilatory response in the bronchial artery upon stimulation was not modified while the increase in blood flow in the superior laryngeal artery was reduced. The ganglionic blocking agent chlorisondamine further reduced the nerve stimulation evoked decrease in vascular resistance in the superior laryngeal artery, but did not influence the response of the bronchial artery. Capsaicin induced a marked increase in blood flow both in the bronchial and superior laryngeal arteries after pre-treatment with atropine, guanethidine and chlorisondamine. After capsaicin tachyphylaxis, the vasodilatation upon nerve stimulation in the bronchial artery and the smaller remaining decrease in vascular resistance in the superior laryngeal artery were strongly reduced. Thus, antidromic stimulation of afferent C fibres may increase blood flow via release of vasodilatory peptides such as tachykinins and calcitonin gene-related peptide. The present findings show that local blood flow in the larynx and upper trachea is regulated by cholinergic and non-cholinergic parasympathetic mechanisms and a small capsaicin sensitive, sensory component. On the other hand, the vagal control of the bronchial circulation seems to exclusively involve capsaicin sensitive sensory nerves. PMID- 2911950 TI - The influence of antihypertensive treatment on the mesenteric arterial structure in spontaneously hypertensive rats. A morphometric study. AB - Spontaneously hypertensive rats (SHR) and stroke-prone spontaneously hypertensive rats (SHRSP) were treated with a combination of a beta 1-blocker (metoprolol) and a calcium antagonist (felodipine) from 1 to 4 or from 4 to 6 months of age. The main trunk and peripheral branches of the mesenteric arterial tree were fixed by immersion and embedded in plastic. The total length of the internal elastic membrane and the media area were measured in cross-sectioned arteries. The ratio between media thickness (m) and luminal radius (ri) was then determined for a calculated, standardized condition, assuming a smooth and circular internal elastic membrane. The treatment caused a significant decrease in blood pressure and a reduction in m/ri ratios in the mesenteric arterial trunk as well as in mesenteric arterial branches when initiated in young as well as in adult SHR and SHRSP, i.e. the therapy efficiently prevents as well as reverses hypertensive arterial changes. The m/ri ratios in the superior mesenteric arterial trunks were significantly smaller in treated 4-month-old SHR and SHRSP than in WKY, although their blood pressures were not fully normalized. There was a marked increase in luminal radius in the young treated rats, possibly secondary to a therapy-induced increase in splanchnic blood flow. PMID- 2911951 TI - A possible ionic basis for dendritic release of dopamine in the guinea-pig substantia nigra. PMID- 2911952 TI - Preoperative evaluation of the elderly patient. AB - Elderly patients are more likely to require surgery and to experience surgical complications than are younger patients. However, age should not be the sole factor in the decision for or against surgery. The surgical risk can be estimated on the basis of both age-related and disease-associated changes in the individual patient. Preoperative evaluation of the elderly patient requires assessment of cardiopulmonary and renal function, immune function, nutritional status and overall homeostatic capacity. PMID- 2911953 TI - Vasectomy technique. AB - Vasectomy is a safe and effective method of male sterilization. The procedure and necessary follow-up care can usually be performed in an office setting. Failure of the procedure may be due to incorrect identification of the vas, recanalization or presence of an accessory vas. PMID- 2911954 TI - The automatic implantable cardioverter-defibrillator. PMID- 2911955 TI - Anorexia nervosa in adulthood. AB - Family physicians and other primary care physicians can work with psychotherapists to provide effective treatment for adult women with anorexia nervosa. The major contributions of family physicians include evaluation and treatment of medical complications and supportive reinforcement of long-term psychotherapy. Family physicians can reassure patients that permanent physical disability can be avoided with successful treatment. PMID- 2911957 TI - New AIDS programs may improve system. PMID- 2911956 TI - Common questions about withdrawal of life support. AB - The case of William Drabick in California reflects mainstream legal trends and answers several common questions about life support. The Drabick court concluded that court intervention is usually not necessary before life support is withdrawn; that formal legal documents are not necessary; that the prior wishes of a patient must be considered in any decision; that when there have been no prior wishes, a surrogate must act in the patient's best interest, and that a court-appointed conservator is not always necessary. PMID- 2911958 TI - Vascular skin lesions associated with AIDS. PMID- 2911959 TI - Toxoplasma peritonitis in AIDS. PMID- 2911960 TI - Patient-controlled analgesia improves pain relief. PMID- 2911961 TI - HIV testing. PMID- 2911962 TI - Cancer risk factors. PMID- 2911963 TI - Managing the difficult patient. PMID- 2911964 TI - Comparison of three techniques for percutaneous balloon aortic valvuloplasty of aortic stenosis in adults. AB - Three different techniques for percutaneous balloon aortic valvuloplasty h have been described: retrograde single balloon, retrograde double balloon, and antegrade techniques. This report describes our experience using the three techniques in twenty-five consecutive procedures. All techniques resulted in a significant decrease in transvalvular pressure gradient and an increase in calculated aortic valve area, without significant difference among the three. There was no increase in the degree of aortic regurgitation after valvuloplasty by any of the techniques. Vascular complications occurred only with the retrograde double balloon technique. Cardiac tamponade during balloon inflation occurred with both the retrograde single and double balloon techniques. Three deaths occurred; two during the antegrade technique and one after the retrograde double balloon technique. Thus, balloon aortic valvuloplasty can be effectively performed using any of the three techniques. However, the differing techniques have inherent advantages in specific situations, as well as potential complications. PMID- 2911965 TI - Improved low energy defibrillation efficacy in man with the use of a biphasic truncated exponential waveform. AB - The standard implantable defibrillator waveform is a truncated exponential of approximately 6 msec duration. This study compares the defibrillation efficacy of a standard monophasic truncated exponential to a biphasic 12 msec truncated exponential waveform in 21 patients undergoing automatic implantable cardioverter defibrillator (AICD) surgery. For the biphasic waveform, the polarity was reversed and remaining capacitor voltage was attenuated by 75% after 6 msec. Two hundred thirty episodes of VF were induced with 115 "matched pairs" of monophasic and biphasic waveforms of identical initial capacitor voltages given over a range from 70 to 600 V (0.35 to 25.7 joules). The biphasic waveform was superior to the monophasic waveform (p less than 0.006), especially for "low energy" defibrillation. For initial voltages less than 200 V, the percent successful defibrillation was 28% for the monophasic waveform versus 64% for the biphasic waveform and from 200 to 290 V (energies less than 6.4 joules) it was 45% versus 69%. There was no difference in the two waveforms in time to the first QRS complex or in the blood pressure following defibrillation. This study shows that a 12 msec biphasic truncated exponential is superior to a 6 msec monophasic waveform for defibrillation in man, especially at energies less than 6.4 joules. The waveform can be achieved in an implanted device without any increase in capacitor size or in battery energy consumption. PMID- 2911966 TI - Pulsed Doppler echocardiographic determination of the time course of left ventricular filling: validation with cineangiography. AB - Several noninvasive techniques are used to evaluate left ventricular diastolic function, but none has optimally characterized the time course of left ventricular filling. We have developed a method to characterize left ventricular filling, by integrating Doppler measurements of flow velocity across the mitral valve. The purpose of the present study was to compare this new method with contrast left ventriculographic assessment of left ventricular filling. Pulsed Doppler studies were obtained within 24 hours of left ventriculography in 15 patients: three normal subjects, seven with coronary disease, two with mitral stenosis, and three with dilated cardiomyopathy. Patients with myocardial infarction, regional wall movement abnormalities, or aortic regurgitation were excluded. Doppler-derived relative left ventricular filling was compared to filling from right anterior oblique left ventriculograms. Doppler and angiographic filling curves were qualitatively different in normal subjects and in patients with mitral stenosis and cardiomyopathy. For individual patients, however, the Doppler and angiographic filling curves were qualitatively similar, with a strong correlation between Doppler and angiographic estimates of percent filling (r = 0.95; p less than 0.001). These preliminary observations suggest that Doppler echocardiography may provide a reliable assessment of the time course of left ventricular diastolic filling. Further studies are warranted and should include more patients with diverse cardiac abnormalities. PMID- 2911967 TI - Semiquantitative evaluation of aortic regurgitation by Doppler echocardiography: effects of associated mitral stenosis. AB - The accuracy of pulsed and continuous wave (CW) Doppler methods for evaluating aortic regurgitation (AR) was compared in patients with and without mitral stenosis (MS), with aortic root angiography as a gold standard. AR was diagnosed with pulsed Doppler echocardiography, by the detection of broad frequency spectral patterns in the isovolumic relaxation time. If these indications were present, AR was graded by examining the extent of diastolic turbulence in the left ventricular cavity (flow mapping method). With CW Doppler echocardiography, AR was diagnosed by the detection of a peak velocity of greater than 2 m/s; if this velocity was attained, AR was graded by measuring the time from the peak velocity to half the peak velocity (half-time method). The angiographic grade corresponded to that determined by the pulsed and CW Doppler methods in 37 and 37 of 46 patients without MS, respectively. Angiographic grade corresponded to the grade determined by the pulsed and CW Doppler methods in 13 and 17 of the 23 patients with MS, respectively. Eight of 10 discrepancies between pulsed Doppler and angiographic grades were due to overestimation of AR by the flow mapping method, apparently because the transmitral jet produces diastolic turbulence in the left ventricular cavity independent of AR. On the other hand, three of six discrepancies between CW Doppler and angiographic grades were due to the incapability of detecting signals of AR by CW Doppler echocardiography. Thus both the pulsed and the CW Doppler methods are useful to evaluate AR in patients without MS. In patients with MS, however, AR is most accurately diagnosed by the detection of AR signals in the isovolumic relaxation time by pulsed Doppler echocardiography, and the degree of AR is more accurately assessed by the CW Doppler half-time method. PMID- 2911968 TI - Ambulatory sudden cardiac death: mechanisms of production of fatal arrhythmia on the basis of data from 157 cases. AB - The study of the tapes of ambulatory patients who died while wearing Holter devices allows us to know the terminal electrical events of death in these cases and which are the electrical triggering mechanisms leading to the terminal event. From the evaluation of seven published series with 10 or more cases, we can see that the most frequent causes of sudden death are ventricular tachyarrhythmias (84% of cases) and bradyarrhythmias (16%). VF was the most frequent ventricular tachyarrhythmia, usually secondary to VT. The rest were due to torsades de pointes in patients often without heart disease but who were taking antiarrhythmic drugs. The VT leading to VF was often preceded by sinus tachycardia or new atrial tachyarrhythmia. Only a small percentage of patients presented ischemic ST changes. In patients who died due to bradyarrhythmias, this was more often due to sinus depression than to atrioventricular block. PMID- 2911969 TI - The noninvasive evaluation of syncope of suspected cardiovascular origin. AB - We have reviewed all available noninvasive diagnostic studies for the evaluation of syncope of suspected cardiovascular origin. This eight-step diagnostic approach covers the majority of available syncopal etiologies. In patients evaluated for syncope, we believe a complete noninvasive evaluation should be performed (if clinically indicated) before performing invasive electrophysiologic studies. PMID- 2911970 TI - Sudden death and silent myocardial ischemia. AB - Recent research indicates that silent myocardial ischemia may play a role in sudden cardiac death. To what extent treatment can reduce occurrence of silent ischemia remains to be assessed. Three classes of silent ischemia patients are identified: type 1--totally asymptomatic; type 2--post myocardial infarction; and type 3--noninfarcted with both silent ischemia and angina. An index of prognostic risk (PR), showing the percent of adverse events attributable to silent ischemia, is calculated to measure the potential impact of successful treatment of silent ischemia on population mortality. Type 1 individuals' PR is estimated at a low 3.8%, suggesting that screening the general asymptomatic population would be unproductive. Type 2 patients exhibit an 80% PR. We lack the empirical information to estimate type 3 patients' PR, but silent ischemia is a recognized adverse prognostic factor in the subgroup exhibiting unstable angina. These results suggest that successful treatment of silent ischemia might favorably influence coronary artery disease patient outcomes. PMID- 2911971 TI - Doppler echocardiographic assessment of the effect of balloon aortic valvuloplasty on left ventricular systolic function. AB - In order to evaluate the effects of balloon aortic valvuloplasty on left ventricular systolic function and ejection dynamics, Doppler echocardiographic studies were performed on 29 patients before and following valvuloplasty. Continuous wave aortic velocity signals were digitized and (with catheterization laboratory before and after valvuloplasty valve areas) were used to calculate: stroke volume; ejection time; ejection rate; time to 25%, 50%, and 75% ejection; accelerative (onset systole to peak velocity) ejection volume, time, and rate; and decelerative (peak velocity to end systole) ejection volume, time, and rate. Following valvuloplasty, there were no significant changes in heart rate; time to 25%, 50%, and 75% ejection; accelerative ejection time; and decelerative ejection time. There were significant increases in stroke volume, total ejection rate, accelerative ejection volume, decelerative ejection volume, accelerative ejection rate, and decelerative ejection rate, and a significant decrease in total ejection time. Balloon aortic valvuloplasty has a significant effect on the dynamics of left ventricular ejection. There is an increase in stroke volume and a decrease in ejection time, with relatively little effect on early systole, and a more pronounced effect in late systole. There are significant increases in accelerative and decelerative ejection volumes and rates, and a decrease in the time required for the last 25% of ejection. By improving the mobility of calcified leaflets, balloon aortic valvuloplasty may reduce the forces opposing forward blood movement during the decelerative phase of aortic ejection. PMID- 2911972 TI - Angiographic demonstration of plaque fissure associated with acute coronary occlusion. PMID- 2911973 TI - Coronary thrombosis induced by coronary spasm without myocardial infarction. PMID- 2911974 TI - Recurrent myocardial infarction and sudden death after sport. PMID- 2911975 TI - Postpartum myocardial infarction in a patient with intermittent ventricular preexcitation. PMID- 2911976 TI - Color Doppler findings in ventricular septal dissection following myocardial infarction. PMID- 2911977 TI - Balloon dilatation of a stenotic dura mater mitral bioprosthesis. PMID- 2911978 TI - An unusual artifactual cause of apparent atrial flutter. PMID- 2911979 TI - Effect of body position on the diagnostic accuracy of the electrocardiogram. PMID- 2911980 TI - Interatrial septal thickening preventing percutaneous mitral valve balloon valvuloplasty. PMID- 2911981 TI - Detection and management of patients with silent myocardial ischemia. PMID- 2911982 TI - Hypertension in the elderly: focus on nicardipine. Proceedings of a symposium. May 26, 1988, Kyoto, Japan. PMID- 2911983 TI - The potential use of nicardipine in cerebrovascular disease. AB - The efficacy of intravenous nicardipine in the prevention of vasospasm after subarachnoid hemorrhage has been investigated in a dose escalation study in 67 patients admitted within 1 week of subarachnoid hemorrhage. Favorable outcomes were noted in 52 patients (78%). Vasospasm was found by arteriography in 31 patients (46%). A dose-related trend was noted. At the lower dose levels, angiographic spasm was observed in 68% and symptomatic vasospasm in 27% of 34 patients. Only eight of 33 patients (24%) treated at the highest dose level (approximately 10 mg/hr) developed arteriographic evidence of vasospasm. Symptomatic vasospasm was diagnosed in only two of 33 patients (6%) treated with this dose. No deaths from vasospasm occurred. Verification of changes in tissue calcium has been obtained from the rat middle cerebral artery occlusion model, and we concluded that nicardipine administered after permanent occlusion may offer protection against cerebral ischemia in this animal model. Nicardipine uptake was greater at the infarct site than in surrounding tissue, with the highest concentration in the area of maximal ischemia. Nicardipine appears to affect changes in Ca2+ more than other ions: it significantly reduced Ca2+ accumulation in the territory of the middle cerebral artery by 60% at 6 hours, and significantly reduced Na+ and K+ shifts in the same territory by 40% and 50%, respectively, at 6 hours. Although much research remains to be done, a wide role for the dihydropyridines in a number of cerebrovascular conditions is emerging. PMID- 2911984 TI - Echophonocardiography in patients undergoing percutaneous mitral balloon valvotomy (PMV): the learning curve of PMV. AB - Percutaneous mitral balloon valvotomy (PMV) was performed in 10 female patients with mitral stenosis; their mean age was 31 +/- 1 years. All patients underwent echophonocardiography (Echophono) before and less than 24 hours after PMV1. Cardiac catheterization and Echophono were repeated 10 and 22 months after PMV1. Eight patients with suboptimal results (defined as a post-PMV mitral valve area [MVA]/less than 1.0 cm2 and mean gradient greater than/10 mm Hg) underwent repeat PMV (PMV2) 10 months after PMV1. The Echophono data are correlated with clinical and hemodynamic changes produced by PMV1 and PMV2. MVA increased from 0.6 +/- 0.1 to 1.1 +/- 0.01 cm2 (p = 0.0009) when PMV1 was performed with a mean effective balloon dilating area (EBDA) of 5 +/- 0.19 cm2. MVA increased from 1.0 +/- 0.1 to 1.7 +/- 0.2 cm2 (p = 0.0002) when PMV2 was performed with larger EBDA (6.4 +/- 0.34 cm2). Two factors related to the learning curve account for the superior result of PMV2: (1) use of larger EBDA and (2) optimal position of the balloons parallel to the long axis of the left ventricle. PMV1 resulted in Echophono changes consistent with decreased severity of mitral stenosis: shortening of Q-S1 from 93 +/- 4 to 82 +/- 4 msec (p less than 0.05) and (Q-S1)-(S2-OS) from 1.8 +/- 0.8 to -0.9 +/- 0.6 (p less than 0.01); prolongation of S2-OS from 75 +/- 5 to 91 +/- 5 msec (p less than 0.05) and increase of EF slope from 7 +/- 1 to 17 +/- 4 mm/sec (p less than 0.05). Compared with PMV1, post PMV2 Echophono showed a further decrease in the severity of mitral stenosis: Q-S1 decreased to 78 +/- 3 msec and (Q-S1)-(S2-OS) decreased to -0.5 +/- 0.3 msec. S2-OS increased to 86 +/- 5 msec and EF slope increased to 22 +/- 4 mm/sec. The hemodynamic and Echophono changes produced by PMV1 and PMV2 persisted at the corresponding follow-up studies. There was no evidence of restenosis. Thus Echophono is a simple, low cost method helpful in the evaluation and follow-up of patients undergoing PMV. PMID- 2911985 TI - Nicardipine in the elderly hypertensive: a review of experience in the United Kingdom. AB - Clinical trials in the United Kingdom have supported those conducted elsewhere in showing that nicardipine is an effective antihypertensive drug in the elderly, with a tendency to produce lower diastolic blood pressure than in younger patients. Side effects are mainly related to vasodilation and are no more common than in younger patients. Nicardipine does not cause any chronic activation of the sympathetic nervous system or the renin-angiotensin system. PMID- 2911986 TI - The clinical performance of nicardipine in elderly hypertensive patients with concomitant diseases. AB - The efficacy and tolerance of nicardipine were evaluated in 2184 ambulatory hypertensive patients with or without concomitant diseases in a 24-week Italian multicenter study. Of the total patient group 1083 had one or more concomitant diseases (diabetes mellitus, coronary heart disease, cardiac failure, mild renal failure, chronic cerebrovascular disease, obstructive lung disease, and peripheral vascular disease); of these patients, 419 were aged over 65 years. Patients were seen on an outpatient basis and after a 2- to 4-week washout period were admitted to the study. The initial nicardipine dose of 20 mg three times a day was titrated in subsequent weeks; thereafter a second antihypertensive drug was added if seated diastolic blood pressure was not reduced below 90 mm Hg. The nicardipine-based therapy significantly lowered seated blood pressure in the whole population (mean 185/102 to 152/86 mm Hg) without clinically and statistically significant differences between the patient subgroups with concomitant diseases. There were no changes in either symptoms, or biochemical and instrumental tests of the concomitant diseases. The incidence of side effects was low; in particular, there was no orthostatic hypotension. Nicardipine-based treatment is therefore effective, safe, and well tolerated in elderly hypertensive patients with concomitant disease. PMID- 2911987 TI - Enzymatic estimation of the extent of irreversible myocardial injury early after reperfusion. AB - To determine whether the extent of infarction can be estimated enzymatically soon after reperfusion, the rate of increase of creatine kinase (CK) activity in plasma early after coronary recanalization was compared with infarct size in 18 dogs and 10 patients. In dogs, reperfusion was initiated 2 to 4 hours after coronary occlusion. CK activity was measured in serial plasma samples and infarct size was assessed histochemically at 24 hours. A substantial and consistent fraction of the total CK appearing in plasma over 24 hours (cumulative CK) appeared in plasma soon after reperfusion, i.e., 21 +/- 2% (SE) within 30 minutes and 38 +/- 3% within 1 hour. The rate of increase of plasma CK activity correlated closely with infarct size when CK release was measured during the first 30 minutes (r = 0.92) or 60 minutes (r = 0.92) after reperfusion (n = 18). Similarly, in patients the rate of increase of CK activity measured within 2.5 hours of the time of reperfusion was closely related to infarct size delineated by positron emission tomography 1 to 2 weeks later (r = 0.93). Thus the rate of appearance of CK in plasma early after reperfusion reflects the extent of irreversible injury ultimately sustained and provides a criterion likely to be useful for prospective identification of patients at high risk after coronary recanalization. PMID- 2911988 TI - Myocardial salvage after regional beta-adrenergic blockade. AB - The aim of the study was to determine whether regional beta-adrenergic blockade via the coronary sinus limited myocardial damage after coronary artery occlusion in the canine model. Accordingly, open-chest anesthetized dogs were randomly allocated to one of three groups: a control group and groups treated with propranolol (in doses of 0.02, 0.2, and 2.0 mg/kg) given either intravenously or via the coronary sinus. The hypoperfused zone (i.e., risk area) and the extent of myocardial damage were assessed by autoradiography and triphenyltetrazolium chloride staining, respectively. Myocardial damage expressed as a percent of the hypoperfused zone was 84 +/- 5% in the control group (n = 9) and 78 +/- 7% (0.02 mg/kg, n = 7, NS), 63 +/- 6% (0.2 mg/kg, n = 7, p less than 0.05), and 62 +/- 7% (2.0 mg/kg, n = 9, p less than 0.02) in the groups receiving intravenous propranolol and 73 +/- 6% (0.02 mg/kg, n = 7, NS), 58 +/- 7% (0.2 mg/kg, n = 7, p less than 0.01), and 44 +/- 9% (2.0 mg/kg, n = 9, p less than 0.001) in groups receiving propranolol via the cardiac veins. There was a significant enhancement of myocardial salvage with increasing doses of propranolol delivered via the cardiac veins (linear regression trend, p less than 0.05). In contrast, myocardial damage expressed as a percent of the hypoperfused zone remained comparable with propranolol doses of 0.2 and 2.0 mg/kg administered intravenously (linear regression trend, NS). IN CONCLUSION: (1) regional beta-adrenergic blockade via the cardiac veins afforded significant myocardial salvage and (2) the regional administration of propranolol resulted in significant reduction of myocardial damage in a dose-dependent fashion. PMID- 2911989 TI - Amelioration by beta-adrenergic blockade of regional myocardial dysfunction induced by coronary artery occlusion after, but not before collateral development in conscious dogs. AB - Effects of beta-adrenergic blockade on regional myocardial dysfunction induced by coronary artery occlusion were studied in chronically instrumented, conscious dogs before (n = 8) and after (n = 7) collateral development. Intravenous atenolol or propranolol produced no beneficial effects on systolic shortening in the area rendered ischemic during 2 minutes of circumflex occlusion, before collateral development. After the collateral development by repetitive 2-minute coronary occlusions, regional asynergy recovered to the preocclusive level during 2 minutes of occlusion. Both atenolol and propranolol significantly improved the peak reductions of regional shortening by 19 +/- 9% and 18 +/- 9%, respectively (p less than 0.05 versus without beta-blockade). These beneficial actions of beta blockade were again noted during atrial tachypacing at matched heart rates of 160 +/- 11 beats/min. Thus the beneficial effects of beta-blockade on regional asynergy during coronary occlusion depend on the level of functional state of the collaterals and cannot be totally accounted for by the reduction in heart rate or by the cardioselectivity. PMID- 2911990 TI - Regional metabolism during coronary occlusion, reperfusion, and reocclusion using phosphorus31 nuclear magnetic resonance spectroscopy in the intact rabbit. AB - Few studies have examined metabolic consequences of coronary occlusion and reperfusion using phosphorus31 nuclear magnetic resonance (31P-NMR) in an intact animal model. Accordingly, we developed a model to study serial changes in myocardial metabolism in the intact open-chest rabbit. Ten animals underwent 20 +/- 2 minutes of regional coronary occlusion and 60 +/- 10 minutes of reperfusion followed by reocclusion. Cardiac-gated 31P-NMR spectra were obtained with a regional surface coil over the ischemic area during baseline, occlusion, reperfusion, and reocclusion conditions. Phosphocreatine fell with both the initial and second ischemic insults to 65% +/- 5% of baseline for the first occlusion (p less than 0.01) and tended to decrease to 89% +/- 8% of baseline for the second occlusion (p = 0.07), with normal levels reattained in the intervening period of reperfusion (99% +/- 5% of baseline, p = NS). Concordant inverse changes were seen with inorganic phosphates. At occlusion levels of inorganic phosphates were 135% +/- 10% of baseline (p less than 0.05) and 139% +/- 10% of baseline at reocclusion (p less than 0.05). Levels of adenosine triphosphate decreased during occlusion to 78% +/- 9% of baseline and were significantly lower than baseline during the second occlusion (75% +/- 5% of baseline, p less than 0.01). The ratio of phosphocreatine to inorganic phosphates, when compared with values at baseline, decreased at occlusion (49.6% +/- 4.7% of baseline, p less than 0.01) and at reocclusion (64.7% +/- 4.9% of baseline, p less than 0.01), with a normal ratio reattained in the intervening period of reperfusion (93.3% +/ 3.1% of baseline, p = NS). We conclude that reperfusion restores levels of phosphocreatine and adenosine triphosphate while returning levels of inorganic phosphates to baseline. Deleterious changes in high-energy phosphate metabolism are not potentiated by reocclusion in this model. 31P-NMR spectroscopy holds promise as a technique to noninvasively monitor intracellular biochemical processes serially during various interventions in the intact animal model. PMID- 2911991 TI - Right ventricular infarction: diagnostic value of ST elevation in lead III exceeding that of lead II during inferior/posterior infarction and comparison with right-chest leads V3R to V7R. AB - The diagnostic accuracy of ST elevation in lead III exceeding that of lead II (ratio III/II greater than 1) in the diagnosis of right ventricular infarction was investigated in 24 autopsied patients with inferior/posterior myocardial infarction on ECG. The results were compared with the diagnostic accuracy of ST elevation greater than or equal to 1 mm in right-chest leads V3R to V7R recorded in the same patients. All had left ventricular infarction documented at autopsy, and 17 (71%) had concomitant right ventricular involvement. The highest specificity (100%) and positive predictive value (100%) were calculated for the right-chest leads, whereas values for ratio III/II greater than 1 were 88% and 91%, respectively. The differences were not statistically significant. It is concluded that differences in ST elevation in leads III and II can be the basis for a diagnosis of right ventricular involvement in ECG-diagnosed inferior/posterior infarction. The diagnosis, however, may be achieved more easily with right-chest leads. PMID- 2911993 TI - A symposium: The goals of antihypertensive therapy--what really counts? March 26, 1988, Atlanta, Georgia. Proceedings. PMID- 2911992 TI - Time-related decrease in sensitivity to ergonovine in patients with variant angina. AB - Eighteen patients with variant angina, a positive ergonovine test, and a favorable response to calcium antagonists were studied by serial ergonovine tests and Holter monitoring to assess the long-term changes in response to ergonovine and the relationship with the spontaneous activity of the disease. The number of patients with a positive test decreased from 18 of 18 in the acute phase to 12 of 18 (66%) at 3 months, 10 of 17 (59%) at 6 months, and five of 17 (29%) at 12 months. The mean dose level of ergonovine associated with a positive response and the percentage of positive tests with ST segment depression increased progressively during follow-up. The results of the ergonovine test were well correlated with the spontaneous activity of the disease in 94%, 83%, 76%, and 71% of the patients at initial observation and at 3, 6 and 12 months, respectively. Thus in patients with variant angina and a favorable response to calcium antagonists, a time-related decrease in sensitivity to ergonovine develops during follow-up. In most patients the response to ergonovine is well correlated with the spontaneous activity of the disease; thus the ergonovine test may be a useful tool in the assessment of the natural evolution of vasospastic angina. PMID- 2911994 TI - Postmarketing surveillance in 70,898 patients treated with a triamterene/hydrochlorothiazide combination (Maxzide) AB - A postmarketing surveillance study on triamterene 75 mg/hydrochlorothiazide 50 mg was conducted by the Philadelphia Association of Clinical Trials on 70,898 patients. These patients received either a whole table (71% of patients) or half tablet (25.2% of patients); 61.3% of all patients continued to take the same dose throughout the 4-week study. The most frequent adverse reactions were generally nonspecific and typical of therapy with a diuretic. The withdrawal rate due to adverse events was significantly lower (p less than 0.005) with the smaller (4.4%) than with the larger (5.6%) dosage. Although not statistically significant overall, reported adverse reactions also favored a lower dose. In general, adverse reactions occurred more frequently in those taking concomitant medications. No significant difference relating to dose was detected in the percentage of initially normokalemic patients who became hyper- or hypokalemic by the end of the study. Older patients tended to achieve goal blood pressure more frequently than did younger patients. These results suggest that the potential for the development of thiazide-induced hypokalemia and other adverse effects appears to be greatly reduced by the use of a potassium-sparing agent combined with a thiazide diuretic, without incurring a greatly increased risk of hyperkalemia and without sacrificing efficacy. PMID- 2911995 TI - Creation of a regional medical-nutrition education network. AB - The Southeastern Regional Medical-Nutrition Education Network (SER-MEN) was developed to coordinate and improve nutrition education in a consortium of the medical schools in Alabama, Florida, Georgia, and South Carolina. SERMEN's central office is at the Medical College of Georgia with the testing office at the University of Alabama at Birmingham. Students, faculty, and consultants in nutrition, education, and computer networking work together on projects on each campus that are coordinated and planned through semiannual meetings. A standardized examination was developed with the Nutrition Test-Item Bank to assess nutrition knowledge at various years of medical students from network schools. Each SERMEN school is connected to a microcomputer system at the central office that provides access to a data base of nutrition education and resources on each campus for developing curricula and syllabi. Funding has been provided by societies, foundations, and government agencies. PMID- 2911996 TI - Relationship of vitamin A and vitamin E intake to fasting plasma retinol, retinol binding protein, retinyl esters, carotene, alpha-tocopherol, and cholesterol among elderly people and young adults: increased plasma retinyl esters among vitamin A-supplement users. AB - We studied the relationships of supplemental and total vitamin A and supplemental vitamin E intake with fasting plasma biochemical indicators of vitamin A and vitamin E nutritional status among 562 healthy elderly people (aged 60-98 y) and 194 healthy young adult (aged 19-59 y) volunteers. All subjects were nonsmokers. For the young adults, plasma retinol was significantly greater in males than in females (p less than 0.01); retinol was not related to supplemental vitamin A intake for either group. Fasting plasma retinyl esters demonstrated a significant increase with vitamin A supplement use. For supplemental vitamin A intakes of 5001-10,000 IU/d, a 2.5-fold increase over nonusers in fasting plasma retinyl esters was observed for elderly people (p less than 0.05) and a 1.5-fold increase for young adults (p greater than 0.20). For elderly people, greater fasting plasma retinyl esters were associated with long-term vitamin A supplement use (greater than 5 y) and biochemical evidence of liver damage. Elderly people who take vitamin A supplements may be at increased risk for vitamin A overload. PMID- 2911997 TI - Vitamin E supplementation in very-low-birth-weight infants: long-term follow-up at two different levels of vitamin E supplementation. AB - This study evaluates the need of vitamin E supplementation in very-low-birth weight infants by long-term follow-up of plasma vitamin E status during the first 15 mo of life, with two different levels of supplementation. The subjects were 51 newborn infants with birth weights less than or equal to 1520 g. During hospitalization the infants were fed human milk. On the third day of life oral vitamin E supplementation of less than or equal to 10 mg/d was started in all infants. In addition, 23 infants selected at random were given intramuscular vitamin E (20 mg/kg/d) during the first 3 d. The data indicate that the 10 mg/d supplement resulted in an adequate plasma concentration of vitamin E. After cessation of supplementation at age 3 mo, the risk of low plasma vitamin E levels increased. Although intramuscular administration resulted in long-lasting increments in mean plasma vitamin E values, some later levels in these infants were marginal. PMID- 2911998 TI - Biotin transport in the human intestine: inhibition by anticonvulsant drugs. AB - The effect of the anticonvulsant drugs carbamazepine and primidone on the transport of biotin in the human intestine was examined with purified brush border membrane vesicles (BBMVs) and basolateral membrane vesicles (BLMVs). Both agents inhibited biotin transport in BBMV in a concentration-dependent manner. The inhibition by both carbamazepine and primidone was competitive (inhibition constant [Ki] of 4.70 and 2.25 mmol/L, respectively) and appeared to be specific because the transport of D-glucose was not affected by different concentrations of these pharmacologic agents. The transport of biotin in BLMV was not affected by carbamazepine or primidone. These results demonstrate that carbamazepine and primidone are competitive inhibitors of biotin transport in the human intestine and that the inhibitory effect is directed toward the substrate transport system at the brush border membrane of the enterocyte. These findings may relate to possible impairment of biotin status in patients on long-term therapy with anticonvulsant agents. PMID- 2911999 TI - Iron absorption in man: ascorbic acid and dose-dependent inhibition by phytate. AB - The dose-dependent inhibitory effect of sodium phytate on iron absorption was studied in man by serving wheat rolls containing no phytates and rolls to which various amounts (seven dose levels between 2 and 250 mg expressed as phytate phosphorus) were added just before serving. Fe in the two kinds of rolls was labeled with two radioisotopes of Fe (55Fe, 59Fe) and the rolls were served on alternate days. The inhibition of Fe absorption was strongly related to the amount of phytate added; 2 mg inhibited absorption by 18%, (p less than 0.001), 25 mg by 64% (p less than 0.001), and 250 mg by 82% (p less than 0.001). The addition of ascorbic acid significantly counteracted the inhibition whereas the corresponding effect of meat was less well defined and only seen at the highest phytate level. The marked inhibition of Fe absorption by phytates and the significant counteracting effect of ascorbic acid have wide nutritional implications. PMID- 2912000 TI - Iron, copper, and zinc status: response to supplementation with zinc or zinc and iron in adult females. AB - Response of iron, copper, and zinc status to supplementation with Zn or a combination of Zn and Fe was assessed in adult females in a 10-wk study. Group Z received 50 mg Zn/d as Zn gluconate; group F-Z received 50 mg Fe as ferrous sulfate monohydrate in addition to the Zn. For Group Z, serum ferritin, hematocrit, and erythrocyte Cu,Zn-superoxide dismutase (ESOD) were significantly lower (p less than 0.05) after 10 wk supplementation compared with pretreatment levels. Serum Zn increased (p less than 0.01) but no change occurred in serum ceruloplasmin, hemoglobin, or salivary sediment Zn with treatment. For Group F-Z ESOD decreased with treatment as did salivary sediment Zn (p less than 0.05). Serum ferritin and serum Zn increased significantly, but hemoglobin, hematocrit, and ceruloplasmin were not affected by this treatment. Supplementation with Zn poses a risk to Fe and Cu status. Inclusion of Fe with Zn ameliorates the effect on Fe but not on Cu status. PMID- 2912002 TI - Clinical nutrition accreditation. PMID- 2912001 TI - Manganese retention in man: a method for estimating manganese absorption in man. AB - Whole-body retention of 54Mn was studied in man by measurements in a sensitive whole-body counter after intake of an extrinsically labeled infant formula. Reproducible retention figures at day 10 were observed after repeated administrations to six subjects; 2.3 +/- 1.1, 3.3 +/- 3.1, and 2.4 +/- 1.4% (means +/- SD) for three separate occasions. Interindividual variation of manganese retention after intake of the same labeled diet was, however, shown to be substantial. Retention at day 10 was 2.9 +/- 1.8% (means +/- SD) and varied from 0.6 to 9.2% when measured in 14 healthy subjects. Large interindividual variations in rate of excretion were observed. The retention measurements for days 10-30, however, could be closely fitted to a single exponential function for each individual. The results regarding intraindividual and interindividual variation in Mn retention indicate that factors influencing Mn absorption can be identified only by repeated administrations using each subject as his/her own control. PMID- 2912004 TI - Estimation of lean body mass by bioelectrical impedance. PMID- 2912003 TI - Relationship of blood pressure, calcium intake, and parathyroid hormone. PMID- 2912005 TI - Body fat distribution and weight loss in obese women. PMID- 2912006 TI - The Surgeon General's Report on Nutrition and Health: policy implications and implementation strategies. AB - The Surgeon General's Report on Nutrition and Health was developed primarily as an authoritative source of information on which to base nutrition policy decisions. It presents a comprehensive review of the evidence that links diet to chronic disease, states the consensus of the Public Health Service on the policy implications of that evidence, and recommends specific dietary changes to reduce disease risk. It identifies reduction of fat consumption as the primary dietary priority and distinguishes recommendations appropriate for the general public from those for special populations. Its consensus on the scientific basis of diet disease relationships establishes a foundation from which to develop policies and programs to implement the report's recommendations. The federal role in implementation is necessary and desirable but not sufficient. Leadership and commitment from the state, local, private, and voluntary sectors are also essential for creation of an environment that promotes improved food choices by individuals. PMID- 2912007 TI - Reliability of fat-free mass estimates derived from total-body electrical conductivity measurements as influenced by changes in extracellular fluid volume. AB - Our study addresses the concern that the relationship between total-body electrical conductivity (TOBEC) measurements and the fat-free mass (FFM) or total body water (TBW) of an individual is altered if significant fluid and electrolyte changes occur. Body composition and TOBEC measurements were obtained from 11 healthy miniature piglets before and after an intraperitoneal injection of physiological saline. The procedure expanded the extracellular fluid (ECF) volume by 11.8-34.1%, which represented an average increase in TBW of 7.9%. The linear regressions that related the preinjection and postinjection estimates of TBW or FFM to the corresponding transformed TOBEC signals were the same. Thus, the prediction equations derived for the untreated piglets accurately predicted both TBW and FFM in the piglets whose volume was expanded. These data suggest that prediction equations derived from healthy subjects should be equally valid for subjects with altered fluid status. PMID- 2912008 TI - Changes in fat-free mass during weight loss measured by bioelectrical impedance and by densitometry. AB - A group of 13 apparently healthy, premenopausal obese women (134-196% ideal weight) volunteered in a weight reduction study for 8 wk on a 4200 kJ (1000 kcal) diet. Before and after the weight reduction period body composition was measured by densitometry and by the bioelectrical impedance method. Changes in fat mass and fat-free mass were calculated. Mean weight loss was 10.0 +/- 2.8 kg and loss of fat-free mass was measured to be 2.3 +/- 1.7 kg (23%) by densitometry and 0.6 +/- 1.9 kg (6%) by impedance measurements. The underestimation of the change in fat-free mass measured by the impedance method could be due to losses of water bound to glycogen after the weight-reduction period. For this reason the impedance method may be not applicable in studies in which changes in glycogen stores can be expected. PMID- 2912009 TI - Accuracy of heart-rate monitoring and activity diaries for estimating energy expenditure. AB - The accuracy of heart-rate monitoring and activity diaries for measuring energy expenditure in free-living individuals was studied in 12 women. Estimates of energy expenditure were calculated from heart-rate monitoring by use of four different prediction equations to describe the relationship between heart rate and energy expenditure. Estimates of energy expenditure from activity diaries were calculated using both individually measured and published values for the energy cost of activities. Energy intake adjusted for changes in body-energy stores was used as a reference. Heart-rate monitoring overestimated group energy expenditure from 2 to 9% and the errors in estimating individual energy expenditure ranged from -53 to 67%. Activity diaries underestimated group energy expenditure by 2-6% and the errors in estimating individual energy expenditure ranged from -39 to 56%. Heart-rate monitoring and activity diaries may prove useful for estimating the energy expenditure of groups but not individuals. PMID- 2912010 TI - Normal caffeine consumption: influence on thermogenesis and daily energy expenditure in lean and postobese human volunteers. AB - Single-dose oral administration of 100 mg caffeine increased the resting metabolic rate of both lean and postobese human volunteers by 3-4% (p less than 0.02) over 150 min and improved the defective diet-induced thermogenesis observed in the postobese subjects. Measurements of energy expenditure (EE) in a room respirometer indicate that repeated caffeine administration (100 mg) at 2-h intervals over a 12-h day period increased the EE of both subject groups by 8-11% (p less than 0.01) during that period but had no influence on the subsequent 12-h night EE. The net effect was a significant increase (p less than 0.02) in daily EE of 150 kcal in the lean volunteers and 79 kcal in the postobese subjects. Caffeine at commonly consumed doses can have a significant influence on energy balance and may promote thermogenesis in the treatment of obesity. PMID- 2912011 TI - Gastric acid secretion, gastrin release, and gastric emptying in humans as affected by liquid meal temperature. AB - We investigated the effect of the temperature of a liquid meal on intragastric temperature, gastric acid secretion, gastrin release, and gastric emptying in normal human subjects. Coffee (360 mL) was infused into the stomach through a nasogastric tube at 58 (steaming hot), 37, or 4 degrees C (ice cold). Intragastric temperature, measured by an intragastric temperature sensor attached to the nasogastric tube, returned to body temperature 16.7 +/- 2.7 min after the hot meal and 23.8 +/- 1.1 min after the cold meal. Gastric acid secretion increased after hot, warm, and cold coffee but the initial temperature of the meal had no effect on gastric acid secretion. The temperature of the meal also had no effect on serum gastrin concentrations, which increased significantly after all the meals. Gastric emptying of hot, warm, or cold coffee meals was similar. These findings indicate that over a wide temperature range, the temperature of a liquid meal has little effect on gastric function in humans. PMID- 2912012 TI - Nonlipid formula components and fat absorption in the low-birth-weight newborn. AB - The relationship between nonlipid formula components and fat absorption in newborns is largely uninvestigated. Two formulas of identical fat blend but different protein quality and acid-base properties were fed to two groups of babies from birth and during 3-5 d balance periods in the third week of life. Babies receiving a formula of higher acidity containing predominantly curd protein absorbed a significantly lower percentage of their fat and nitrogen intake than babies receiving a curd-and-whey protein formula (fat absorptions of 73 +/- 11.0 and 85 +/- 8.0%, means +/- SD, p less than 0.04; N absorptions of 90 +/- 3.0 and 93 +/- 1.0%, p less than 0.03, respectively). The feces of the curd formula babies contained a smaller proportion of long-chain, saturated fatty acids and a larger proportion of shorter-chain and unsaturated fatty acids. Fatty acid type and triglyceride structure are not the only factors influencing fat absorption in newborns. Other formula components may need modification to achieve maximum fat absorption. PMID- 2912013 TI - Evaluation of urinary 3-methylhistidine excretion in infection by measurements of 1-methylhistidine and the creatinine ratios. AB - When 3-methylhistidine (3MH) excretion is used as an indicator of myofibrillar protein catabolism, there are restricting factors, such as meat intake, incorrect 24-h urine collections, and a large interindividual variation in basal excretion. 1-Methylhistidine (1MH) was previously suggested as an indicator of meat intake. We studied the basal urinary excretion of 1MH and whether this was influenced by infection and we compared the use of 3MH vs the 3MH:creatinine ratio (3MH:Cr) in detecting changes during infection. The basal excretion of 1MH was 84.9 mumol/24 h and its creatinine molar ratio (1MH:Cr) was 7.4 x 10(-3) with no change during infection. Because 1MH:Cr was significantly increased in 4 of 14 patients, their 3MH values were considered influenced by meat intake and thus discarded. Among the remaining 10 patients, 9 showed a significant individual increase in 3MH:Cr during infection compared with only 4 in 3MH. This was due to a higher precision in 3MH:Cr despite the concomitant significant increase in urinary creatinine excretion. PMID- 2912014 TI - Calorie-restricted low-fat diet and exercise in obese women. AB - The effects of caloric restriction and exercise on body composition, resting metabolic rate (RMR), and maximal oxygen uptake (VO2 max) were studied for 16 wk in 26 premenopausal obese women. Exercise (X) vs nonexercise (NX) was crossed with a low-fat, ad libitum-carbohydrate (AL) diet vs a restricted (R) (800 kcal) low-fat, high-carbohydrate diet in a 2 x 2 factorial design. Subjects were randomly assigned to one of the four treatment groups. Body-weight and percent fat losses were significant (p less than 0.05) in all groups but greater in subjects assigned to the R diet (p less than 0.05) and/or X (p less than 0.10) groups. Exercise increased (p less than 0.01) VO2 max but neither exercise nor diet influenced fat-free mass or RMR (kcal.m-2.h-1), both of which remained unchanged over time. A program similar to that followed by the ALX group is recommended for long-term weight control and overall health. PMID- 2912015 TI - Decreased caloric intake in normal-weight patients with bulimia: comparison with female volunteers. AB - Patients with bulimia (binge-purge syndrome) frequently complain that they consume a very restrictive diet to avoid gaining weight. To investigate this claim, 23 hospitalized bulimic patients were assessed daily for body weight, caloric intake, macronutrient diet content, activity measures, and body composition estimates during weight-stable periods. Bulimic patients ate fewer kilocalories per kilogram body weight (22.1 +/- 4.6 kcal/kg) than did age-matched normal women (29.7 +/- 6.5 kcal/kg) but had similar activity levels and body composition. Clinical variables, such as history of laxative abuse, anorexia, or obesity, and physiological characteristics, such as body weight, activity level, or dietary content, could not account for this difference in caloric consumption. Bulimic patients tended to eat a diet lower in fat and higher in protein than did control subjects. These results agree with observations of increased efficiency of caloric utilization in obese patients and support patient complaints of a tendency to gain weight easily. PMID- 2912016 TI - Sustained depression of the resting metabolic rate after massive weight loss. AB - To assess potential long-term effects of weight loss on resting metabolic rate (RMR), the RMRs of seven obese women were measured by indirect calorimetry before weight loss, during a protein-sparing modified fast, and for 2 mo while at a stable reduced weight. Body composition was also determined at each interval. RMR significantly decreased 22% (p less than 0.01) with initiation of the modified fast. RMR values during the modified fast and during the maintenance diet at stable reduced weight were not different and all were significantly lower than the prediet RMR. Loss of lean tissue could not account for the decrease because changes in RMR per fat-free mass paralleled the total RMR reduction. A sustained decrement in RMR accompanied weight loss and persisted for greater than or equal to 8 wk despite increased caloric consumption and body weight stabilization. PMID- 2912017 TI - Phase II study of diaziquone in untreated advanced gastric carcinoma. A Southwest Oncology Group Study. AB - Twenty-nine patients with a diagnosis of advanced adenocarcinoma of the stomach with gross unresectable or measurable residual disease and no prior therapy were entered into a study utilizing diaziquone (AZQ) in an intermittent 3-week schedule of 40 mg/m2. Of 28 eligible patients, 1 (4%) experienced a partial response, 7 (25%) had stable disease of no response, and 18 (64%) developed increasing disease. Two (7%) were unevaluable. Median survival was 3.8 months. Major toxicities were myelosuppression and gastrointestinal, 11 of which were considered to be life-threatening. AZQ used as a single intermittent agent appears to have no significant activity to warrant use in untreated advanced gastric carcinoma. However, recognizing the short plasma half-life of AZQ, significant responses by other schedules of administration are not precluded. PMID- 2912018 TI - Oral idarubicin in measurable gastric cancer. AB - Seventeen patients with advanced gastric adenocarcinoma, previously untreated with chemotherapy, have been included in a Phase II study with idarubicin (IDA), 15 mg/m2/day, orally, for three consecutive days every 3 weeks. All cases had measurable disease. Sixteen of 17 patients are evaluable for response. Complete or partial responses were not observed. Two patients had partial response less than 50%, one patient no change, and the remaining 13 patients disease progression. The median leukocytes and platelets nadir was 3600 and 186,000/mm3, respectively. Gastrointestinal toxicity was mild. The median total cumulative dose of IDA was 90 mg/m2 (range 45-180 mg/m2). Clinical cardiac toxicity was not observed. IDA, at the dose and by the route used, is not active in gastric cancer. PMID- 2912019 TI - Radiation therapy for squamous cell carcinoma of the supraglottic larynx. AB - Sixty-five patients with invasive squamous cell carcinoma of the supraglottic larynx received irradiation with curative intent between 1975 and 1984, with a 5 year actuarial survival of 48% and a local control rate of 70%. Five-year survivals for clinical Stages I, II, and III + IV were 60, 53, and 52%, respectively; local control rates were 88, 76, and 63%, respectively. These patients included one treated with preoperative irradiation, 35 treated with surgery followed by postoperative irradiation, and 29 treated with radiation therapy alone. In the surgery plus irradiation group, 5-year local control was 93% for clinical Stages I + II (14 patients), and 61% for clinical Stages III + IV (21 patients). Three patients had pathologic Stage II disease, with the remainder demonstrating a higher pathologic than clinical stage. Multiple positive nodes predisposed to local/regional recurrence, while no relationship could be established between recurrence and extracapsular nodal spread, positive margins, emergency tracheostomy, total versus less-than-total laryngectomy, radiation field size, radiation dose, or delay until radiation therapy, probably because of patient numbers. Six patients, five with positive nodes, developed distant metastases, and three developed second primary tumors outside the head and neck region. In the radiation therapy alone group, 5-year local control rates were 86, 59, and 53% for clinical Stages I (7 patients), II (11 patients), and III + IV (11 patients), respectively. However, three of four Stage II local/regional failures were surgically salvaged for periods greater than 30 months, for an ultimate Stage II local control of 89%. No relationship could be established between local control and radiation dose or field size, again probably because of small patient numbers. Three patients developed distant metastases, and eight developed second malignancies, one within the irradiated volume. Fifteen patients developed acute toxicity during irradiation, and there were eight chronic complications, five requiring surgery; toxicity was more common in the group treated with radiation alone. Radiation therapy alone with surgical salvage is an effective, function-preserving treatment for clinical Stages I and II carcinoma of the supraglottic larynx, and appears to yield local control and survival comparable with that of combined irradiation and surgery in more advanced disease. PMID- 2912020 TI - Phase II trial of N-methylformamide in advanced renal cancer. AB - N-methylformamide (NMF) (800-1,000 mg/m2 i.v. day 1) was given to 14 patients with measurable, advanced renal cell carcinoma in this Phase II trial. Treatment was repeated every 28 days. Significant toxicities included drug-induced hepatitis along with moderate nausea and vomiting. No objective responses were seen although several patients had stable disease with treatment for prolonged periods. NMF is not an active agent in renal cell cancer when administered by this schedule. PMID- 2912021 TI - Neoadjuvant or definitive alternating chemotherapy and radiotherapy for infiltrating bladder cancer. AB - Thirty-two patients with infiltrating bladder cancer were treated with transurethral resection followed by one course of alternating chemoradiotherapy before radical cystectomy (group A, 20 patients) or two courses as definitive procedure (group B, 12 patients). One course consisted of: cisplatin 20 mg/m2 i.v. and 5-fluorouracil 200 mg/m2 i.v. for 5 consecutive days, the first and the fourth weeks; radiotherapy 20 Gy in 10 fractions in the second and third weeks. At the seventh week the same integrated therapy was restarted in group B. All 32 patients were evaluable for toxicity after the first course: no grade IV toxicity was observed. Significant increase in hematological toxicity was observed in 12 patients who received the second course of chemoradiotherapy: two patients had grade IV toxicity, and five patients had grade III. Fifteen patients of group A underwent radical cystectomy: 40% had a pathological (p) complete response (CR) and 13.3% a partial response Five patients in group A did not receive either the second course of therapy or cystectomy because of age (three patients), vascular obliteration (one patient) and enteritis (one patient). Actuarial disease-free survival in group A is 78% at 21 months. All patients of group B obtained clinical (c) CR and all but one have no evidence of disease at a median follow-up of 10 months (range 6-13). The high pCR and cCR obtained in patients of group A and group B, respectively, appears promising. A longer follow-up and a larger number of patients is required to determine the role of this integrated treatment. PMID- 2912022 TI - A phase II trial of intermittent leukocyte interferon and high dose chlorambucil in the treatment of non-Hodgkin's lymphoma resistant to conventional therapy. AB - Thirteen patients with advanced non-Hodgkin's lymphoma who previously failed conventional chemotherapy protocols were treated with a combination of alpha interferon (IFN) 6,000,000 units i.m. days 1-5 and 8, plus chlorambucil (CLB) 16 mg/m2 days 5-9 repeated every 4 weeks. There were five complete responses (CRs) and one partial response (PR) (46% total responses) with mean duration of remission of 456+ days. Responses were obtained in low and intermediate grade lymphomas. Toxicity was acceptable and easily managed. It is unlikely that IFN alone using this low dose intermittent schedule is responsible for the remissions. The combination of the two agents appears to be an effective treatment modality. IFN may be functioning as a biological response modifier when used in combination with a cytotoxic agent. PMID- 2912023 TI - The case in developing countries for routine postoperative radiotherapy after mastectomy in patients with histologically positive axillary nodes. PMID- 2912024 TI - Phase II trial of spirogermanium and vindesine in malignant glioma. AB - Fifty-four adults with recurrent malignant glioma were treated on an Eastern Cooperative Oncology Group (ECOG) trial. All had previous radiation therapy, and 70% had previous chemotherapy. They were assigned to either vindesine 3 mg/m2 weekly or spirogermanium 80 mg/m2 three times weekly with escalation to 120 mg/m2. The response was 4% to vindesine, and 8% to spirogermanium. The duration of response was 53 days for a patient who had clinical improvement only, but greater than 151 days and greater than 1066 days for two patients who had achieved a greater than 50% reduction in tumor size by computed tomography (CT). The toxicities were hematologic for vindesine and neurologic for spirogermanium. Neither agent seems to have sufficient efficacy to warrant further trials in previously treated glioma patients. PMID- 2912025 TI - Cardiac response to upper gastrointestinal endoscopy. AB - In 54 subjects, cardiac function was investigated during upper gastrointestinal endoscopy with a Holter electrocardiorecorder. The heart rate of patients who were premedicated with an anticholinergic agent increased more than did that of patients who received no premedication. In the group who received no anticholinergic premedication, sinus tachycardia was evident during endoscopy, but the only clinically important change was in one patient who converted to atrial flutter from atrial fibrillation. The heart rate increased during endoscopy among patients undergoing the procedure for the first time, but it did not increase in the patients who had previously undergone endoscopy. These results show that endoscopy is a relatively safe examination from the view point of cardiac risk when performed without the administration of an anticholinergic agent, but that cardiac patients should be monitored carefully. The endoscopist should also take into consideration the psychological state of the examinees. PMID- 2912026 TI - The ileum is the major site of absorption of vitamin B12 analogues. AB - Non-cobalamin vitamin B12 analogues constitute a significant percentage of total corrinoids in human serum. The source and means of absorption of analogues and their significance are largely unknown. We studied the sites of production and absorption of B12 analogues by measuring serum vitamin B12 and analogues in 93 patients with various gastrointestinal diseases: pernicious anemia (PA), ileal resections, ileitis, Crohn's colitis, ulcerative colitis, and irritable bowel syndrome (IBS). Patients with PA had normal analogue levels that were unchanged or that rose during cessation of B12 administration. Patients with IBS, Crohn's colitis, ulcerative colitis, and total colectomies had B12 analogues in the normal range. Patients with diseased or resected ileums had low B12 and analogues. These data suggest that serum B12 analogues are absorbed in the ileum by a mechanism independent of intrinsic factor, and that colonic bacteria and endogenous metabolism of vitamin B12 do not contribute significantly to their level. PMID- 2912027 TI - Fecal fat concentration in the differential diagnosis of steatorrhea. AB - Many approaches have been proposed to differentiate between steatorrhea due to pancreatic insufficiency and intestinal disease. Bo-Linn and Fordtran recently suggested that fecal fat concentration (FFC) is a useful screening test for this distinction. Our aim was to validate their result in a large group of patients. Fecal fat concentrations were calculated for 613 fecal fat tests in 538 patients. Included were 88 patients with pancreatic steatorrhea (13 pancreatic carcinoma, 6 cystic fibrosis, and 69 chronic pancreatitis) and 525 with nonpancreatic steatorrhea. The mean FFC of patients with pancreatic disease (15.0 +/- 1.9 g%, mean +/- SEM) was significantly higher than that of patients with other diseases causing malabsorption (8.9 +/- 0.3 g%, p less than 0.001). Forty-two percent of patients with pancreatic steatorrhea had an FFC below 10 g%. The overlapping of the FFC of steatorrhea due to pancreatic disease and that produced by celiac disease, gastric resection, and other conditions suggests that this approach does not differentiate between pancreatic and intestinal steatorrhea. PMID- 2912028 TI - Cigarette smoking in Crohn's disease. AB - Crohn's disease is a chronic disease of unknown etiology. Previous reports have suggested that cigarette smoking may be associated with the development of Crohn's disease. To examine this association, we conducted a case-control study of patients referred to a single practice over a 7-month period. The cigarette smoking habits of 115 patients with Crohn's disease were compared with the cigarette-smoking exposure of 109 patients with the irritable bowel syndrome. Patients with Crohn's disease were more likely to smoke at the time of symptom onset than were irritable bowel syndrome controls (age and sex adjusted odds ratio 3.71, 95% confidence interval 1.93-7.13). After the diagnosis of Crohn's disease, patients were less likely to quit smoking (odds ratio 0.35, 95% confidence interval 0.18-0.69) than controls. This study demonstrates an association and a temporal relationship between cigarette smoking and Crohn's disease. For the exposure to be considered an etiologic factor for disease, biologic plausibility and pathophysiologic mechanisms require elucidation. PMID- 2912029 TI - Rectosigmoid motility in patients with quiescent and active ulcerative colitis. AB - We studied the pathophysiology of diarrhea in ulcerative colitis by evaluating and comparing rectosigmoid motility before, during, and after a 900-cal meal in healthy subjects, patients with quiescent ulcerative colitis, and patients with active ulcerative colitis. Three intraluminal pressure transducers were used for recording of rectosigmoid motility. Motility during fasting, eating, and after eating a meal was similar in patients with quiescent disease and controls. Motility increased significantly during eating in controls, but not in patients with quiescent disease. In patients with active colitis, motility was significantly reduced during fasting, eating, and after eating, compared with controls. Motility increased significantly during eating in patients with active disease. Propagated activity was similar in the three study groups; therefore, the decreased motility was due to decrease in segmental contractions. These findings suggest that diarrhea in patients with active colitis may be related to the loss of normal segmental contractions which delay distal stool transport. PMID- 2912030 TI - Bilateral ureteral obstruction: an unusual complication of pancreatitis. AB - A case of bilateral ureteral obstruction associated with alcoholic pancreatitis in a 40-yr-old male patient is reported. Although pancreatitis complicated by pseudocyst formation has been known to involve intra- and extraabdominal organs, bilateral ureteral obstruction has not been reported. We postulated that in the case reported herein, periureteral fat necrosis involving both ureters was the primary etiological mechanism. PMID- 2912031 TI - Heterotopic pancreas: gastric outlet obstruction secondary to pancreatitis and pancreatic pseudocyst. AB - Heterotopic pancreas, usually a silent gastrointestinal anomaly, may become clinically evident when complicated by a pathologic process. We report a unique case in which pancreatitis and pseudocyst formation in an antral lesion produced gastric outlet obstruction. The nature of heterotopic pancreas, its diagnosis, and management are discussed. PMID- 2912032 TI - Idiopathic benign stricture of the common bile duct. AB - An unusual case of idiopathic benign stricture of the intrapancreatic portion of the common bile duct is described. Because of the absence of a history of pancreatitis or an operation upon the biliary tract, the obstruction was thought to be due to malignancy. However, histologic studies of tissues removed by pancreaticoduodenectomy established that the lesion was a benign stricture. PMID- 2912033 TI - Hepatoportal arteriovenous fistula treated with detachable balloon embolotherapy. AB - Hepatic artery to portal vain fistulas were first reported in 1892. Symptoms of portal hypertension usually occur within weeks to months, once the fistula develops. Various attempts at surgical occlusion and embolization, with varying results, have been reported. This report is of a 33-yr-old woman who, 23 yrs after an automobile accident, was admitted with ascites and diagnosed as having a right hepatic artery-to-portal vein fistula (RHAPVF), which was successfully occluded via detachable balloon embolic therapy. The ascites resolved within 3 days of the embolotherapy, and subsequent follow-up revealed no recurrence of ascites during the next 18 months. PMID- 2912034 TI - Severe hemolysis after distal splenorenal shunt. AB - We report a case of severe hemolysis after distal splenorenal shunt. Hemolysis was suddenly recognized at the time splenorenal venous anastomosis was completed, and it continued on the operative day and the first postoperative day. After the shunt, the intraoperative splenic venous blood flow was approximately double its previous level, as measured by electromagnetic flowmeter. Angiographic partial splenic embolization was performed on the second postoperative day, and then hemolysis stopped suddenly. This suggested that hemolysis after distal splenorenal shunt was related to increased splenic blood flow and acceleration of erythrocyte destruction. PMID- 2912035 TI - Gross hematuria following sclerotherapy of esophageal varices in patients with cystic fibrosis. AB - We report two patients with portal hypertension secondary to cystic fibrosis who developed transient gross hematuria following injection sclerotherapy of esophageal varices. Both patients developed this complication within 6 h of sclerosing sessions during which sodium morrhuate was used. Each cleared her hematuria within 4 days without developing oliguric renal insufficiency. Subsequent sclerotherapy was associated with no untoward effects. These are the only two pediatric patients among 40 whose varices we have sclerosed who have developed gross hematuria at the time of sclerotherapy, and they are our only two patients undergoing sclerotherapy who have had cystic fibrosis. The factors rendering them vulnerable to renal or urinary tract insult in the absence of other systemic complications are unclear. However, the therapeutic endoscopist should be cognizant of this potential adverse reaction when performing sclerotherapy. PMID- 2912036 TI - Metastatic hypernephroma to the ampulla of Vater: an unusual cause of malabsorption diagnosed at endoscopic sphincterotomy. PMID- 2912037 TI - Aeromonas hydrophila colitis presenting as medically refractory inflammatory bowel disease. PMID- 2912038 TI - Collagenous enterocolitis or colitis? PMID- 2912039 TI - Body weight and prognostic indicators in breast cancer. Modifying effect of estrogen receptors. AB - The relations of body weight, height, and Quetelet index to axillary node involvement at diagnosis, estrogen receptor status, and histologic features of the primary tumor were examined in 656 patients with a newly diagnosed infiltrating breast carcinoma first treated in Quebec City from July 1982 to December 1984. Node involvement increased with body weight and Quetelet index. This association was more regular and much stronger among patients with estrogen receptor-positive tumors than among those with estrogen receptor-negative breast cancers. Among patients with estrogen receptor-positive tumors, the percentage with involved nodes at diagnosis increased regularly from 32.9% among lean patients (Quetelet index less than 21 kg/m2) to 65.6% among obese women (Quetelet index greater than 27 kg/m2). This trend was seen even after adjustment for age and tumor size. In contrast, among patients with estrogen receptor-negative breast cancers, the association of weight and Quetelet index with node involvement were weak and irregular. The modifying effect of estrogen receptor status on the relation of obesity to node involvement was apparent in pre- and post-menopausal women. Body weight and Quetelet index were not related to estrogen receptor status or to any of the measured histologic features of breast tumors including nuclear grade, histologic grade, tubule formation, mitotic activity, and size of nucleus of cancer cells. These findings suggest that the observed deleterious effect of obesity on breast cancer prognosis is unlikely to be an artifact of delayed diagnosis in overweight patients. It may be due to hormonal changes associated with increases in body weight. PMID- 2912040 TI - Breast cancer before age 45 and oral contraceptive use: new findings. AB - The relation between the risk of breast cancer before 45 years of age and oral contraceptive use was examined in a case-control study conducted in New York, Philadelphia, Baltimore, and Boston from 1983 to 1986 of 407 patients with breast cancer and 424 controls. With allowance for confounding, for ever use, the multivariate relative risk estimate was 2.0 (95% confidence interval (CI), 1.4 2.9). For less than 10 years of use, the estimate approximated 2.0 in all categories of duration, including less than three months; for 10 or more years of use it was 4.1 (95% CI, 1.8-9.3). The association was apparent in virtually all subgroups examined, including younger and older women, and women at low and high underlying risk of breast cancer. Contrary to some previous reports, the association was not stronger for use before a first term pregnancy or at an early age. The results suggest that oral contraceptive users, particularly those with very long durations of use, may be at increased risk of breast cancer. However, information bias, particularly for short-term use, could not be ruled out. There may also have been selection bias if oral contraceptive users were under more intensive medical surveillance. It has not been possible to reconcile the findings of the various studies to date, including the authors' earlier results showing no association. The latter results were derived from data collected using methods almost identical to those used in the present study. PMID- 2912041 TI - High density lipoprotein cholesterol levels among US adults by selected demographic and socioeconomic variables. The Second National Health and Nutrition Examination Survey 1976-1980. AB - The distribution of serum high density lipoprotein cholesterol (HDL cholesterol) levels was determined on a nationally representative sample of 9,625 adults aged 20-74 years, as part of the Second National Health and Nutrition Examination Survey, 1976-1980 (NHANES II). Mean HDL cholesterol levels were higher in women compared with men (an age-adjusted difference of 8.9 mg/dl for whites and 4.4 mg/dl for blacks). HDL cholesterol levels were higher in blacks compared with whites (an age-adjusted difference of 7.4 mg/dl for men and 2.8 mg/dl for women). All differences were statistically significant (p less than 0.01). These relations remained after stratification by age, income, poverty index, education, body mass index, alcohol consumption, cigarette smoking, and physical activity. For whites, HDL cholesterol levels were highest in the highest category of earnings, whereas blacks generally had lower levels of HDL cholesterol with increased earnings. In a multivariate model, important predictors of higher HDL cholesterol levels were being female, being black, and reporting a higher frequency of alcohol consumption. Less strongly related were age, years of education, and reported high physical activity. Smoking and body mass index were strongly negatively related to HDL cholesterol levels. The findings in this national study support previous findings in selected populations in the United States. PMID- 2912042 TI - Methods and prevalence of non-insulin-dependent diabetes mellitus in a biethnic Colorado population. The San Luis Valley Diabetes Study. AB - The San Luis Valley Diabetes Study was undertaken to determine the prevalence, risk factors, and complications of non-insulin-dependent diabetes mellitus in Hispanics and Anglos (non-Hispanic whites), using a geographically based case control design. The study was conducted in two southern Colorado counties that include 43.6% Hispanic and 54.9% Anglo persons. Medical practice records were reviewed to identify medically diagnosed diabetics. Controls without diabetes were identified by a two-stage random sample of households. Diabetics (n = 343) and controls (n = 607) attended a clinic where an oral glucose tolerance test or current hypoglycemic therapy confirmed or diagnosed non-insulin-dependent diabetes mellitus. The age-adjusted prevalence of confirmed non-insulin-dependent diabetes mellitus was 21/1,000 in Anglo males and 44/1,000 in Hispanic males, accounting for non-response. For Anglo females, the prevalence was 13/1,000 compared with 62/1,000 for Hispanic females, accounting for nonresponse. Previously undiagnosed non-insulin-dependent diabetes mellitus was also higher among Hispanics. There was a 2.1-fold excess of confirmed non-insulin-dependent diabetes mellitus among Hispanic males and a 4.8-fold excess among Hispanic females, consistent with the excess non-insulin-dependent diabetes mellitus among Hispanics reported from comparable studies. Non-insulin-dependent diabetes mellitus is a major chronic disease problem for persons of Hispanic ethnicity. PMID- 2912043 TI - Large fluctuations in body weight during young adulthood and twenty-five-year risk of coronary death in men. AB - The hypothesis that large fluctuations in weight during young adulthood are associated with increased risk of coronary heart disease was investigated by comparing the 25-year mortality of three groups of middle-aged men with distinctly different patterns of self-reported weight during young adulthood: 98 men who reported large gains and large losses, 133 who reported large gains and no losses, and 178 who reported no substantial change in weight. They were selected from a cohort of 2,107 men aged 40-56 years who participated in the Western Electric Study from 1957 through 1983. The 25-year crude risk of coronary death was 26% in the "gain and loss" group, 15% in the "gain only" group, 14% in the "no change" group, and 17% in the remaining 1,550 men. After adjustment for age and major coronary risk factors, the relative risk of coronary death in the gain and loss group as compared with the no change group was 2.0 (95% confidence interval 1.2-3.5). Risk of death from cancer was highest in the gain only group, and risk of death from all causes combined was lowest in the no change group. These results support the concept that large changes in weight during young adulthood increase the risk of coronary disease and of cancer. PMID- 2912044 TI - An outbreak of influenza A/Taiwan/1/86 (H1N1) infections at a naval base and its association with airplane travel. AB - In late October 1986, an outbreak of influenza-like illness was detected at the Naval Air Station in Key West, Florida. Between October 10 and November 7, 1986, 60 active duty personnel reported experiencing a respiratory illness characterized by fever, cough, sore throat, and myalgia. Influenza A/Taiwan/1/86 (H1N1) virus was recovered from three symptomatic patients. Forty-one (68%) of 60 case-patients belonged to a 114-person squadron that had traveled to Puerto Rico for a temporary assignment from October 17-28, 1986. Among squadron members, the attack rate for persons previously vaccinated with the 1986-1987 trivalent influenza vaccine and for those unvaccinated was the same (37%). Transmission of infection among squadron personnel appeared to have commenced in Key West and continued in a barracks in Puerto Rico and aboard two DC-9 aircraft that transported the squadron back to Key West on October 28. There was no evidence that the outbreak spread to the surrounding civilian communities in Puerto Rico or Key West. This was the first reported outbreak of respiratory illness due to influenza A/Taiwan/1/86 (H1N1) in the continental United States in the 1986-1987 influenza season. PMID- 2912045 TI - Congenital rubella syndrome in the United States, 1970-1985. On the verge of elimination. AB - The National Congenital Rubella Syndrome Registry, a passive surveillance system, and the Birth Defects Monitoring Program, a newborn hospital discharge data set, are used to monitor the incidence of congenital rubella syndrome in the United States. Reports to the registry contain clinical and laboratory data which allow cases to be classified into six categories according to the likelihood of having congenital rubella syndrome. The monitoring program records newborn discharge diagnoses, without detailed information, of a nonrandom sample of about one fourth of the births in the United States annually. To evaluate the two systems and to estimate the actual incidence of congenital rubella syndrome, the authors collected hospital discharge summaries on all cases as reported by the monitoring program from 1970-1985 and classified them by the registry criteria. Of the 392 cases reported to the monitoring program during 1970-1985, 24% (n = 93) could be classified as confirmed or compatible compared with 79% (n = 415) of the 526 cases reported to the registry (rate ratio = 3.3; 95% confidence interval (CI) 2.9-3.8). Diagnosis of congenital rubella syndrome was made during the neonatal period for 68% (263 of 389) registry cases for whom such data were available. When the Lincoln-Peterson capture-recapture method of estimating population size for independent surveillance systems was used, an estimated 1,064 confirmed and compatible cases (95% CI 668-1,460) diagnosed during the neonatal period occurred during 1970-1979, for an average of 106 cases per year. During 1980-1985, an estimate of 122 neonatal confirmed and compatible cases (95% CI 8-236) occurred, for an average of 20 cases per year. A downward secular trend in the incidence of congenital rubella syndrome beginning in 1980 was observed. The registry detected 22% of all neonatal confirmed and compatible cases, the monitoring program detected 8%, and the two systems combined detected a total of 28%. The results indicate that congenital rubella syndrome may be on the verge of elimination in the United States. PMID- 2912046 TI - Bacteriuria in pregnancy. Frequency and risk of acquisition. AB - A total of 3,254 pregnant women attending two antenatal clinics in Goteborg, Sweden, were screened for bacteriuria. The coverage of the pregnant population in the areas served by the two clinics was estimated to be 88%. Of the women who were registered at the two clinics, 99% took part in at least one screening; 71% were screened during each of the three intervals. The high frequency of screening of the women made it possible to estimate the risk of acquiring bacteriuria during pregnancy. This risk increased with the duration of pregnancy from 0.8% of bacteriuric women in the 12th gestational week to 1.93% at the end of pregnancy. The risk of onset of bacteriuria was highest between the ninth and 17th gestational weeks. The 16th gestational week was the optimal time for a single screening for bacteriuria calculated as the number of bacteriuria-free gestational weeks gained by treatment. PMID- 2912047 TI - Factors associated with past household exposure to tobacco smoke. AB - With data that were obtained in a private census in Washington County, Maryland, in 1963, the prevalence of household exposure to tobacco smoke was determined, and factors associated with passive smoke exposure were identified among 48,342 white adults. In 1963, 52% of men and 72% of women were exposed to smoke from others at home. Smokers of both sexes were more likely to live with other smokers than were nonsmokers. However, 30% of men who never smoked and 64% of women who never smoked lived with smokers. Marriage was a primary determinant of exposure for women but not for men, with 75% of married women who did not smoke exposed but only 38% of unmarried women who did not smoke exposed. Conversely, among men who did not smoke, exposure was more common among those who were not married than among those who were married. After control for other factors associated with exposure, exposure prevalence increased with years of school among men who did not smoke but decreased with years of school among women who did not smoke. Exposure prevalence also varied slightly with housing quality and location of residence. Smoking by spouse was an accurate reflection of household exposure for women but not for men; 88% of the exposure among women who did not smoke was contributed by the spouse, whereas only 62% of exposure among men who did not smoke was from the spouse. PMID- 2912048 TI - Papanicolaou test coverage without a cytology registry. AB - Because of problems in following women over time, it is difficult to assess the degree of Papanicolaou test coverage among the general population. In a region with no cytology register or recall system, the authors used data from Manitoba's universal health insurance plan to determine the actual number of women tested and the number of tests per woman from 1970 to 1984 inclusive. By cross-sectional analysis, the proportion screened annually was found to be highest for women aged 25-34 years (50-57%) and decreased with increasing age. The proportion screened annually for women over 25 remained essentially unchanged over the 15 years (34 39%). From a probability sample of women aged 35-64 years (n = 17,711), it was found that 91% had at least one test and 78% had three or more tests over 15 years. Untested women tended to be single, older, and from rural or remote areas. To assess multiple testing, the authors used the cross-sectional data to determine the number of women with two or more tests per year. About 4% of women had two or more tests annually, and 60% of these were accompanied by a diagnosis suggestive of an abnormal gynecologic condition. On the basis of published recommended schedules for Papanicolaou testing, the authors conclude that the widespread testing in Manitoba shows that the voluntary system has been working fairly well. High rates of coverage were achieved but with a degree of overtesting for some women. PMID- 2912049 TI - Selection of neighborhood controls for a study of coronary artery disease. AB - This report describes the selection process for a neighborhood control group recruited between February 1985 and July 1986 to augment a hospital-based case control study investigating the relation of traditional and nontraditional risk factors to coronary artery atherosclerosis. A total of 219 cases with angiographically defined coronary artery disease residing within a 60-mi (96-km) radius of Winston-Salem, NC, were assigned to surveyors to be matched. Thirty seven per of the study population were rural, 92% were white, 58% were male, and 52% were older than 50 years of age. One hundred and eighty-seven controls were age-(+/- five years), sex-, and race-matched pairwise to cases. After locating the residence of the case, the surveyor systematically visited neighboring households to ascertain eligibility status of residents. To achieve a match, a maximum of three visits was made to the neighborhood; up to 25 households were surveyed per visit. Refusal rate was less than 5% of eligible matches. Young white urban males were the easiest to match, while rural females, especially older persons, were the most difficult. Average time to complete an assignment included 129 minutes for travel, 237 minutes for surveying the neighborhood, and 62 minutes for clerical tasks. Average distance traveled was 85 mi (136 km) per case. As expected, the time and distance to complete a case were greater in rural than urban areas. The average cost per case was $122.97. PMID- 2912050 TI - A study of repeatability of dietary data over a seven-year period. AB - A repeatability study of dietary intake has been carried out using 94 control subjects from a previously reported case-control study of diet and colorectal cancer. Dietary histories readministered on average seven years after an initial interview were used to estimate intake of various macro- and microdietary components. Comparisons of current intake with intake of seven years previously yielded good reliability for macrocomponents among subjects reporting no dietary change during the time period. Reliability was poorer for microcomponents and for subjects reporting a dietary change. Comparisons were also made between diet measured seven years previously with subjects' recall of that diet. It is concluded that current diet is at least as reliable a measure of past diet as that assessed by a questionnaire addressed to the past period. PMID- 2912051 TI - Estimating the morbidity risk of illness from survey data. AB - A method is proposed for using survey data to estimate lower and upper bounds for the lifetime risk of an illness (morbidity risk). The mathematical model used, which is based on a three-state Markov process, assumes that the illness is irreversible, but allows differential mortality. The data required include information on age at onset collected from prevalent cases, and an estimate of the magnitude of differential mortality, which ordinarily must come from published research. The method is illustrated using data from a community survey of psychiatric illness conducted in Edmonton, Alberta, Canada. PMID- 2912052 TI - Epidemiologic programs for computers and calculators. A microcomputer program for multiple logistic regression by unconditional and conditional maximum likelihood methods. AB - A frequent procedure in matched case-control studies is to report results from the multivariate unmatched analyses if they do not differ substantially from the ones obtained after conditioning on the matching variables. Although conceptually simple, this rule requires that an extensive series of logistic regression models be evaluated by both the conditional and unconditional maximum likelihood methods. Most computer programs for logistic regression employ only one maximum likelihood method, which requires that the analyses be performed in separate steps. This paper describes a Pascal microcomputer (IBM PC) program that performs multiple logistic regression by both maximum likelihood estimation methods, which obviates the need for switching between programs to obtain relative risk estimates from both matched and unmatched analyses. The program calculates most standard statistics and allows factoring of categorical or continuous variables by two distinct methods of contrast. A built-in, descriptive statistics option allows the user to inspect the distribution of cases and controls across categories of any given variable. PMID- 2912053 TI - A dietary and risk factor questionnaire and analysis system for personal computers. AB - The authors report the adaptation of a dietary and risk factor questionnaire and analysis system for use with IBM (or compatible) personal computers. This system includes a flexible computer-assisted interview program which may be modified to suit investigator needs while preserving a standard output format. It also includes a nutrient analysis program for calculation of usual dietary intake. Each of these two major components has its own set of utilities and options, so that investigators may tailor the system to particular research areas. The nature and capabilities of the two main programs are described, as well as the development of the underlying system and the general flow of data in the system. PMID- 2912054 TI - Re: "Animal product consumption and subsequent fatal breast cancer risk among Seventh-day Adventists". PMID- 2912055 TI - Re: "Occupational working conditions and preterm birth: a reliable scoring system". PMID- 2912056 TI - Re: "Epidemiology of rabies virus variants: differentiation using monoclonal antibodies and discriminant analysis". PMID- 2912058 TI - National Kidney Foundation, 18th annual scientific meeting. Abstracts. PMID- 2912057 TI - Re: "Evaluation of two food frequency methods of measuring dietary calcium intake". PMID- 2912059 TI - Proceedings from the International Symposium on Preventing the Kidney Disease of Diabetes Mellitus: Public Health Perspectives. Washington, DC, December 16-18, 1987. PMID- 2912060 TI - The problem of diabetic renal failure in the United States: an overview. AB - Native Americans, blacks, and other minorities are at high risk for diabetic renal failure, most of which is caused by non-insulin-dependent diabetes. Many of these patients receive care in publicly supported health programs. Recent evidence of the efficacy of hypertension control in slowing the decline in renal function and our ability to detect those at highest risk for renal deterioration with inexpensive microalbuminuria tests suggest major opportunities for concerted efforts to reduce the incidence of end-stage renal disease. Guidelines for management of high-risk patients are needed to translate effective management strategies into routine clinical practice. PMID- 2912061 TI - The predictive value of microalbuminuria. AB - An elevated urinary albumin excretion (termed microalbuminuria) has been proposed as a predictor for later development of clinical diabetic nephropathy (hypertension, falling glomerular filtration rate [GFR], and urinary albumin excretion greater than 300 mg/24 h). However, review of the original reports on the predictability of microalbuminuria revealed a concomitant presence of elevated BP and a propensity to falling GFR. Thus, the predictability of microalbuminuria rests on the added evaluation of BP and GFR. Additional investigation is needed to address the possibility that microalbuminuria and either a rising BP or a falling GFR or both indicates established diabetic nephropathy rather than predicting its development. PMID- 2912062 TI - 'Microalbuminuria' and diabetes: a critique--assessment of urinary albumin excretion and its role in screening for diabetic nephropathy. AB - Abnormal albumin excretion in the range not previously detectable by routine clinical methods can now be readily quantified, and has been shown to predict the development of clinically significant nephropathy in insulin-dependent diabetes mellitus (IDDM) and to predict excess mortality in non-insulin-dependent diabetes mellitus (NIDDM). Albuminuria of this degree has been inappropriately called "microalbuminuria," a misleading term which should be abandoned. In IDDM, persistent minimal elevation of albumin excretion predicts the development of more severe proteinuria and clinical diabetic nephropathy, which frequently progresses to renal failure. In NIDDM, the predictive value for renal failure remains to be established, but excess mortality occurs in those with abnormal albumin excretion, suggesting that it is an indicator of generalized vascular disease. However, the normal range of albumin excretion in older subjects is not well established. The relationship of glomerular injury to mildly elevated albumin excretion is uncertain. Several means of reducing the excretion rate have been described, but whether these can halt or prevent progression of glomerular injury is unknown. Thus, at the present time detection of mildly elevated albumin excretion and intervention to reduce the incidence of diabetic nephropathy or other diabetes-related complications fail to meet generally accepted criteria for prescriptive screening. However, such measurements of albumin excretion provide an important tool for research into the natural history and pathogenesis of diabetic nephropathy. PMID- 2912063 TI - Biologic variation of urinary albumin: consequences for analysis, specimen collection, interpretation of results, and screening programs. AB - Studies on the analytic and biologic variability of albumin concentration, albumin/creatinine ratio, and albumin excretion rate in first morning, random, and 24-hour urine specimens from healthy subjects suggest that (1) first morning specimens are preferred, (2) results should be expressed as albumin concentration, (3) assay of creatinine confers little advantage, (4) an analytical precision of coefficient of variation (CV) less than 18% is satisfactory, and (5) semiquantitative or qualitative analyses are suitable for screening programs. The intraindividual variation of albumin concentration in first morning specimens from diabetics is such that no threshold value gives the desired 100% nosological sensitivity. However, a threshold value of 30 mg/L confers 100% specificity, and a single abnormal result therefore requires initiation of therapy. Patients with negative results should continue to be monitored regularly. PMID- 2912064 TI - New parameters to monitor the progression of diabetic nephropathy. AB - The possible differential elimination of the anionic IgG4 and of the other cationic IgG molecules whose pH differs but whose other characteristics are similar, has been hypothesized as a possibly useful parameter in monitoring preclinical diabetic nephropathy. An enzyme-linked immunosorbent assay method has been developed, based on a sandwich technique with subclass-specific antiimmunoglobulin monoclonal antibodies, which detects about 2 ng/mL IgG4. A sensitive radioimmunoassay method has been used to detect IgG. Normoalbuminuric, microalbuminuric, and macroalbuminuric patients, together with normal control subjects, were included in the cross-sectional study. Whereas IgG levels were elevated, as expected, in macroalbuminuric patients, it was interesting to note that IgG4, but not total IgG, levels were elevated in microalbuminuric patients. The IgG4/IgG ratio was increased almost to the same extent in microalbuminuric and macroalbuminuric patients. These findings are strongly in favor of the selective elimination of the acid medium-sized protein, IgG4, in incipient diabetic nephropathy. The measurement of immunoglobulin subclasses in the urine appears to be a promising parameter to characterize and subgroup diabetic patients with preclinical diabetic nephropathy. PMID- 2912065 TI - Alternate-day prednisone therapy in children with IgA-associated nephritis. AB - IgA nephropathy (IgAN) leads to renal failure in up to 30% of affected children and adults. There is currently no consensus on therapy in IgAN. Six patients with risk factors for disease progression were identified based on clinical or histologic findings. These patients were treated with alternate-day prednisone for 12 to 60 (mean, 36) months and followed for 28 to 60 (mean, 54) months. Follow-up biopsies were available in four patients. At last examination all treated patients had normal urinalysis and serum creatinine level. Follow-up biopsies showed stable or improved glomerular histology in three of four patients. One patient had a slight worsening of the interstitial disease. No steroid toxicity was observed. The outcome of these treated patients was compared with that of 15 comparable patients from another center who received no treatment and with patients from two published clinical pathology series. A normal urinalysis was found at follow-up in all treated patients, compared with one of 15 untreated patients (P = 0.003). None of the patients in the published series with comparable disease had normal urinalysis at follow-up. End-stage renal disease or renal insufficiency occurred in seven of 15 untreated and no treated patients (P = 0.19). The data strongly support the need for a prospective control trial of prednisone therapy in IgAN. PMID- 2912066 TI - Genetic testing of identity and relationship. PMID- 2912067 TI - Galactocerebrosidase activity in somatic cell hybrids derived from twitcher mouse/control human fibroblasts is associated with human chromosome 17. AB - Somatic cell hybrids derived from twitcher mouse cells and from control human fibroblasts were selected by two different methods. One method utilized 6 thioguanine-resistant twitcher cells as a parental line and the other used neomycin-resistant control human fibroblasts as a parental line so that hybrid lines could be selected in either HAT or in G-418 medium, respectively. The hybrid lines were analyzed for galactocerebrosidase activity. Since the twitcher cell lines are deficient in galactocerebrosidase activity, the presence of this activity in these hybrid lines depends upon the presence of human chromosome contents. Both galactocerebrosidase-positive and -deficient hybrid lines were analyzed for their human chromosome contents by the use of isozyme markers. In hybrids derived from both selection methods the expression of galactocerebrosidase activity was associated with the presence of human chromosome 17 marker isozymes. This was confirmed cytogenetically by means of trypsin-banded Giemsa staining of intact human chromosome 17 in three galactocerebrosidase-positive hybrid lines. PMID- 2912068 TI - Identifying pedigrees segregating at a major locus for a quantitative trait: an efficient strategy for linkage analysis. AB - Having found evidence for segregation at a major locus for a quantitative trait, a logical next step is to identify those pedigrees in which major-locus segregation is occurring. If the quantitative trait is a risk factor for an associated disease, identifying such segregating pedigrees can be important in classifying families by etiology, in risk assessment, and in suggesting treatment modalities. Identifying segregating pedigrees can also be helpful in selecting pedigrees to include in a subsequent linkage study to map the major locus. Here, we describe a strategy to identify pedigrees segregating at a major locus for a quantitative trait. We apply this pedigree selection strategy to simulated data generated under a major-locus or mixed model with a rare dominant allele and sampled according to one of several fixed-structure or sequential sampling designs. We demonstrate that for the situations considered, the pedigree selection strategy is sensitive and specific and that a linkage study based only on the pedigrees classified as segregating extracts essentially all the linkage information in the entire sample of pedigrees. Our results suggest that for large scale linkage studies involving many genetic markers, the savings from this strategy can be substantial and that, compared with fixed-structure sampling, sequential sampling of pedigrees can greatly improve the efficiency for linkage analysis of a quantitative trait. PMID- 2912069 TI - Two point mutations are responsible for G6PD polymorphism in Sardinia. AB - The human X-linked gene encoding glucose 6-phosphate dehydrogenase (G6PD) is highly polymorphic; more than 300 G6PD variants have been identified. G6PD deficiency in different geographical areas appears to have arisen through independent mutational events, but within the same population it may also be heterogeneous. One example is the island of Sardinia, where careful clinical and biochemical studies have identified four different G6PD variants. We cloned and sequenced the four G6PD variants from Sardinia and found that only two mutations are responsible for G6PD deficiency in this area: one mutation is the cause of the G6PD Seattle-like phenotype, a milder form of G6PD deficiency; the other mutation is responsible for all forms of very severe G6PD deficiency in Sardinia and, possibly, in the Mediterranean. PMID- 2912070 TI - Lowe oculocerebrorenal syndrome: DNA-based linkage of the gene to Xq24-q26, using tightly linked flanking markers and the correlation to lens examination in carrier diagnosis. AB - The Lowe syndrome (LS), or oculocerebrorenal syndrome, has been studied using DNA based linkage analysis, and the findings have been correlated with the result of a thorough ophthalmologic examination. It was found that the LS gene was linked to markers in the Xq24-q26 region and that the locus DXS42 was the most closely linked marker, giving a LOD score of 3.12 at zero recombination distance. Combined with earlier data, this forms the basis for carrier detection and prenatal diagnosis by using tightly linked flanking markers. A summary of our and other data suggests that the loci DXS17, DXS11, DXS87, and DXS42 are located on the proximal side, and DXS86 and DXS10 on the distal side of the Lowe locus. In isolated cases of LS the question of whether the mother is a carrier of the mutation arises. It was found that a lens examination with slit-lamp illumination and a count of the total number of lenticular opacities is a reliable method of ascertaining the carrier state. PMID- 2912072 TI - Requirements for submission of manuscripts. PMID- 2912071 TI - The economics of clinical genetics services. III. Cognitive genetics services are not self-supporting. AB - We investigated the amount of time required to provide, and the charges and reimbursement for, cognitive genetics services in four clinical settings. In a prenatal diagnostic center, a mean of 3 h/couple was required to provide counseling and follow-up services with a mean charge of $30/h and collection of $27/h. Only 49% of personnel costs were covered by income from patient charges. In a genetics clinic in a private specialty hospital, 5.5 and 2.75 h were required to provide cognitive services to each new and follow-up family, respectively. The mean charge for each new family was $25/h and for follow-up families $13/h. The amount collected was less than 25% of that charged. In a pediatric genetics clinic in a large teaching hospital, new families required a mean of 4 h and were charged $28/h; follow-up families also required a mean of 4 h, and were charged $15/h. Only 55% of the amounts charged were collected. Income from patient charges covered only 69% of personnel costs. In a genetics outreach setting, 5 and 4.5 h were required to serve new and follow-up families, respectively. Charges were $25/h and $12/h, and no monies were collected. In all clinic settings, less than one-half of the total service time was that of a physician, and more than one-half of the service time occurred before and after the clinic visit. In no clinic setting were cognitive genetics services self supporting. Means to improve the financial base of cognitive genetics services include improving collections, increasing charges, developing fee schedules, providing services more efficiently, and seeking state, federal, and foundation support for services. PMID- 2912073 TI - Reduced serum inhibition of platelet-activating factor activity in preeclampsia. AB - We determined in normal nonpregnant (group 1) women, normal pregnant (group 2) women, and patients with preeclampsia (group 3) the serum inhibition of platelet activating factor activity, the presence of detectable amounts of platelet activating factor in the blood, and platelet responsiveness in vitro to platelet activating factor, and to other agonists (adenosine diphosphate, collagen, and ristocetin), and prostacyclin (prostaglandin I2). In patients with preeclampsia (group 3) the serum inhibition of platelet-activating factor activity was significantly lower than that in groups 1 and 2. However, no detectable amounts of platelet-activating factor were observed. The mean values of platelet aggregation induced by platelet-activating factor, adenosine diphosphate, collagen and ristocetin, and the prostaglandin I2-inhibitory concentration of 50% which is inversely correlated with platelet sensitivity to prostaglandin I2, were not significantly different between groups 2 and 3. It is suggested that in preeclampsia the defect in serum inhibitory potential of platelet-activating factor--induced platelet aggregation may contribute to the disturbance in the homeostatic balance between proaggregant and antiaggregant substances. PMID- 2912074 TI - Fetal premature atrial contractions associated with hydralazine. AB - Echocardiography documented fetal premature atrial contractions after maternal hydralazine treatment for hypertension. No signs of fetal congestive heart failure were noted, and other tests of fetal surveillance remained reassuring. The arrhythmia spontaneously subsided after discontinuation of hydralazine. A possible cause-and-effect relationship of hydralazine and premature atrial contractions has not been previously reported. PMID- 2912075 TI - The biologic significance of cytologic atypia in progestogen-treated endometrial hyperplasia. AB - Eighty-five menopausal women (mean age 56 years) with endometrial hyperplasia without (65 patients, group 1) and with cytologic atypia (20 patients, group 2) were followed up prospectively from 2 to 12 years (mean 7 years) to shed insight into their respective response to oral medroxyprogesterone acetate therapy. In group 1 9 of 65 patients (14%) had persistence, 4 (6%) had recurrence, and none developed carcinoma. In group 2 10 of 20 patients (50%) had persistence and 5 had recurrence with cytologically atypical disease. Five of 20 patients (25%) developed adenocarcinoma at 2 to 7 years (mean 5.5 years) after starting medroxyprogesterone acetate therapy. The data suggest that most women with hyperplasia respond to progestogenic therapy and are not at increased risk of developing cancer. The patients with an unfavorable response to medroxyprogesterone acetate and a significant elevation in cancer risk can be identified on the basis of cytologic atypia. PMID- 2912076 TI - Detection of bacterial vaginosis in Papanicolaou smears. AB - In a prospective study of 145 women, bacterial vaginosis was clinically diagnosed in 46 women. Compared with clinical diagnosis of bacterial vaginosis, detection of so-called clue cells in Papanicolaou smears showed a sensitivity of 90% and a specificity of 97%. The positive and negative predictive values were 94% and 95%, respectively. The study results indicate that demonstration of clue cells in Papanicolaou smears is a useful method for identification of women with probable bacterial vaginosis. This provides a basis for the use of archival material in retrospective studies with regard to possible links between bacterial vaginosis and development of cervical cancer. PMID- 2912077 TI - Abnormal fetal heart rate patterns and placental inflammation. AB - Can acute inflammation in the placental membranes, amniotic fluid, or both, predispose to the development of abnormal fetal heart rate patterns? One hundred cases in which bradycardia was noted were compared with 48 cases in which abnormal fetal heart rate patterns did not occur. Case and control subjects were matched to provide an equivalent risk of developing ascending infection in the two groups. Fetoplacental weight ratio and the presence of other placental diseases were also considered. The presence of acute inflammation in the umbilical cord (p = 0.03), amnion (p = 0.01), and choriodecidua (p = 0.03), and higher grades of inflammation in chorionic plate (p = 0.03) were linked to the presence of abnormal fetal heart rate patterns. No other placental factors were associated with increased risk of fetal bradycardia. The association of abnormal fetal heart rate patterns with acute inflammation suggests that intra-amniotic inflammation is important in the genesis of fetal bradycardias. The inflamed amniotic fluid could alter fetal metabolism via effects on the pulmonary or gastrointestinal systems or effects on umbilical and chorionic vessels. PMID- 2912078 TI - Case-fatality rates for tubal sterilization in U.S. hospitals, 1979 to 1980. AB - To update a 1977 to 1978 case-fatality estimate for tubal sterilization in U.S. hospitals, we reviewed the medical records of women reported by the Commission on Professional and Hospital Activities to have died after tubal sterilization procedures in 1979 or 1980. We project that the most reasonable case-fatality rate estimate is slightly greater than 9 per 100,000 sterilizations if all deaths associated with the procedure are considered. Rate estimates that assume minimum and maximum numbers of all associated deaths in our sample are approximately 6 per 100,000 and 10 per 100,000 sterilizations, respectively. However, when only deaths that can be attributed to sterilization per se are considered, the most reasonable case-fatality rate is estimated at between 1 and 2 per 100,000 procedures, a lower rate than previously reported. Rate estimates that assume minimum and maximum numbers of attributable deaths in our sample are approximately 1 per 100,000 and 5 per 100,000 sterilizations, respectively. These results further indicate that death attributable to tubal sterilization is rare. PMID- 2912079 TI - The preterm nonstress test: effects of gestational age and length of study. AB - The application of the nonstress test between 24 and 32 weeks' gestation has been limited by high rates of "false" nonreactivity in normal fetuses, by use of term criteria, and the lack of age-appropriate interpretative standards. To establish such standards, we studied 30 normal fetuses undergoing 90-minute fetal heart rate recordings at 2-week intervals from 24 to 32 weeks' gestational age. Using a specially programmed computer we quantified (1) baseline fetal heart rate, (2) incidence of 10- and 15-beat accelerations, and (3) incidence of fetal heart rate decelerations. With a criterion of three 15-beat accelerations per 30 minutes 91% of tests were reactive within 90 minutes. A criterion of three 10-beat accelerations per 30 minutes was associated with 100% reactivity within 60 minutes. Suitable interpretative criteria may be established for nonstress tests before 32 weeks' gestation by extending the testing time or by decreasing the minimum amplitude required of fetal heart rate accelerations. PMID- 2912081 TI - Appraising a clinical journal article in obstetrics and gynecology. AB - Although some physicians have the opportunity to participate in a journal club during residency, many infrequently receive formal instruction on how to critically evaluate a journal article. Systematic guidelines for appraising a clinical journal article are presented and illustrated with examples. Considering each guideline in its respective order may lead to a better understanding of what the literature may offer one's practice. PMID- 2912080 TI - Effects of estrogen on urethral function in women with urinary incontinence. AB - In a prospective study, 2 gm of conjugated estrogen vaginal cream was administered daily for a total of 6 weeks in a group of 11 postmenopausal women with urodynamically proved genuine stress incontinence. Midurethral cytologic studies and a complete clinical and urodynamic evaluation were performed twice at 6-week intervals. Clinically, six of the 11 patients (54.5%) were cured or improved significantly after estrogen treatment, whereas the other five patients (45.5%) were clinically unchanged. The favorable clinical response correlated with urodynamic findings of increased urethral closure pressure and improved abdominal pressure transmission to the proximal urethra (p less than 0.05); in the patients who had a poor clinical response to estrogens, no significant changes in urethral dynamics were noted. Changes in urethral cytologic findings also correlated well with clinical and urodynamic findings. Patients with a favorable response to estrogen showed a maturation change from transitional to intermediate squamous epithelium (p less than 0.02), whereas nonresponders showed no significant changes in urethral cells. PMID- 2912082 TI - Correlation of human spermatozoa heparin binding with the zona-free hamster egg in vitro penetration assay. AB - The purpose of our research was to determine whether heparin-binding characteristics of human spermatozoa are related to fertilizing potential, as determined by the hamster egg in vitro penetration assay. Penetration rates were standardized (hamster egg in vitro penetration assay index) by comparison with semen from fertile controls in each bioassay. Saturation of heparin-binding domains was achieved in 100% of raw ejaculates (prewash), but in only 53% of "swim-up" (postwash) samples. The dissociation constants ranged from 0.31 to 48.75 nmol/10(6) cells, and binding site concentrations from 0.47 to 20.82 x 10(17) binding sites/cell. Heparin-binding affinity was significantly greater in prewash compared with postwash samples (p less than 0.01). In prewash samples the number of binding sites differed significantly between subjects having low and high penetration indices (5.67 +/- 1.05 vs 2.01 +/- 0.34 x 10(17) binding sites/cell, p less than 0.05). In prewash samples, binding affinity for heparin significantly correlated with hamster egg in vitro penetration assay indices (R2 = 0.142, p less than 0.05). In contrast, the number of binding sites in prewash samples was negatively correlated with hamster egg in vitro penetration assay indeces (R2 = 0.201, p less than 0.05). These data indicate that the heparin binding assay may prove to be a rapid, sensitive, and inexpensive means of assessing fertilizing potential of human spermatozoa. PMID- 2912083 TI - Umbilical artery creatine kinase brain-band isozyme as a predictor of neonatal periventricular-intraventricular hemorrhage. AB - In low-birth-weight neonates, an elevation in the percentage of creatine kinase brain-band isozyme in the umbilical artery was significantly correlated with future development of neonatal grade III and grade IV periventricular intraventricular hemorrhage, when compared with levels in those neonates who did not show periventricular-intraventricular hemorrhage or who developed grade I and grade II periventricular-intraventricular hemorrhage (p = 0.025). In these neonates the relative levels in maternal venous, umbilical arterial, and umbilical venous samples indicated that the source of the isozyme was fetal. PMID- 2912084 TI - An obstetric analysis of fifty consecutive pregnancies after transfer of cryopreserved human embryos. AB - This report describes the obstetric outcome in 50 pregnancies resulting from the transfer of human embryos that had been cryopreserved for up to 2 years. The duration of cryopreservation did not influence the pregnancy rate after thawed embryo transfer. Thirty-one babies have been born from 28 pregnancies and a further seven pregnancies are currently in the second and third trimesters. Twenty-eight percent of the pregnancies failed to progress beyond the first trimester. One pregnancy was terminated at 22 weeks' gestation because of severe fetal malformation. Important antenatal events included premature uterine activity in six patients although only one patient with a singleton pregnancy ultimately was delivered prematurely. Retroplacental hemorrhage occurred in four patients but was of clinical consequence in only one. There was a high incidence of breech presentation at term in singleton pregnancies (12%). The cesarean section rate in this series was 21%. An international registry of cryopreserved pregnancies would facilitate data collection in this relatively new clinical field. PMID- 2912085 TI - Diagnosis of trisomy 18 in monozygotic twins by cordocentesis. AB - The incidence of monozygotic twins with trisomy 18 is 1 in 1,000,000 births. We report a case diagnosed prenatally with lymphocyte culture from fetal blood samples obtained by cordocentesis. Fetal growth lag and structural malformations detected by ultrasonography indicated chromosomal abnormality. A saline solution infusion technique ensured that cordocentesis obtained a sample from each twin. PMID- 2912086 TI - A functional and structural study of the innervation of the human uterus. AB - We characterized the innervation of human myometrial tissues by electrical field stimulation and electron microscopy. Nerve-specific parameters (pulse duration 0.6 msec) were used for electrical field stimulation to selectively activate intrinsic nerves. In specimens from nonpregnant, nonparous women (n = 6), tetrodotoxin (10(-6) mol/L) significantly reduced the response to electrical field stimulation by 70%. Contractions to electrical field stimulation were also inhibited to 60% by atropine (10(-5) mol/L) as well as by guanethidine (10(-5) mol/L) and phentolamine (10(-5) mol/L). Propranolol (10(-5) mol/L) had no detectable effect. We obtained similar results from about 50% of the specimens from nonpregnant, parous women (n = 15). The contractile responses of specimens from the term pregnant uterus (n = 13) to electrical field stimulation were not influenced by tetrodotoxin. Ultrastructurally we found nerve profiles in close proximity to muscle cells. About 30% of nerve varicosities in tissues from nonpregnant, nonparous patients could be classified as adrenergic (small, dense cored vesicles), 53% as cholinergic (small, agranular vesicles), and about 17% as indeterminant (sometimes large, dense-cored vesicles). However, nerve varicosities were rarely observed in term pregnant specimens. These results indicate the presence of tetrodotoxin-sensitive, excitatory innervation of human myometrium consisting of alpha-adrenergic and cholinergic components. Furthermore, denervation may be nearly complete at term and recovery of innervation occurs at a considerable length of time after delivery. PMID- 2912087 TI - Pharmacodynamic study of maturation and closure of human umbilical arteries. AB - The contractile effects of 19 factors on isolated human arterial segments at term pregnancy were quantified, and 14 contractile agents were similarly applied to preterm (23 to 35 weeks) umbilical arteries. Responses to potassium chloride were used to normalize the data. At comparison with the term vessel, the preterm artery contracted more to angiotensin II and arachidonic acid and was more sensitive to oxytocin. Contractions were greater in term arteries to vasopressin, norepinephrine, prostaglandin D2, and prostaglandin E2 but similar in both group of arteries to bradykinin, histamine, acetylcholine, and prostaglandin F2 alpha. Neuropeptide Y, linoleic acid, uridine triphosphate, and thrombin were ineffective. Hyperoxia inconsistently induced weak, short-lived contractions. Contractions to cooling manifested marked desensitization and tachyphylaxis. Serotonin was the only agonist that displayed the pharmacodynamic features most likely to be important for closure: potency, efficacy, and long duration of action (greater than 2.5 hours). It was postulated that cellular elements surrounding umbilical vessels are primary sources of vasoactive agents that are important to closure of the fetoplacental circulation at birth. PMID- 2912088 TI - The effect of estrogen on placental delivery after fetectomy in baboons. AB - In baboons, the placenta remains in situ and functional with respect to the potential for aromatization after removal of the fetus (fetectomy). Fetectomy therefore was used to study effects of the fetus and estrogen on placental delivery. By term, serum estradiol levels in untreated, intact baboons had increased to 4 to 8 ng/ml, and fetoplacental delivery occurred on day 184 +/- 1 (mean +/- SE). Fetectomy at midgestation resulted in a nondetectable serum estradiol level and a marked decline in progesterone level; however, placentas were maintained in situ and were delivered on day 171 +/- 6. After fetectomy therefore the initiation of placental delivery and, presumably, myometrial contractility did not require an elevation in estrogen. Administration of estradiol (1 to 10 mg/day) to baboons after fetectomy resulted in normal serum estradiol concentrations, but placental delivery was prevented. When estrogen was discontinued on days 215 to 250, the serum estradiol level declined, and placental delivery occurred on day 262 +/- 18, a value greater than in intact baboons or untreated baboons after fetectomy (p less than 0.001). Thus estrogen prevented placental delivery in baboons after fetectomy. PMID- 2912089 TI - Calcium ion-dependent regulation of uterine smooth muscle thin filaments by caldesmon. AB - Native thin filaments were extracted from rabbit uterus by the procedure of Marston and Smith. The protein content was actin, tropomyosin, and caldesmon in molar ratios of 1:0.2:0.03. Some filamin, myosin, and calcium-binding protein were also present. The thin filaments activated skeletal or smooth muscle myosin magnesium adenosine triphosphatase at least 30-fold. Activation was regulated by Ca2+; maximum observed Ca2+ sensitivity was greater than 10 times. The thin filaments were dismantled into component proteins by the method of Smith and Marston. Actin and actin-tropomyosin-activated myosin magnesium adenosine triphosphatase, but the activation was not Ca2+-regulated. Added caldesmon inhibited adenosine triphosphatase activation by as much as 80%, with 50% inhibition at 1 caldesmon per 50 actin. Caldesmon inhibition was not Ca2+ dependent, but inhibition could be reversed by further addition of Ca2+ and calmodulin. It is concluded that the thin filaments of uterine smooth muscle are Ca2+ regulated and that this regulatory system could be involved in control of uterine smooth muscle contractility. A mechanism for thin filament regulation, mediated by caldesmon, is proposed. PMID- 2912090 TI - Blunted vasoreactivity in pregnant guinea pigs is not restored by meclofenamate. AB - Pregnant women show a reduced pressor responsiveness to angiotensin II, but the mechanism responsible in unclear. We sought to determine whether reduced pressor responsiveness was due to decreased vasoreactivity and the involvement of increased vasodilator prostaglandin production in decreases observed. We found that pregnancy decreased systemic vascular resistance and the systemic vascular resistance response to angiotensin II infusion but not to phenylephrine hydrochloride infusion in awake, unstressed guinea pigs. The decreased systemic vascular resistance response to angiotensin II in the pregnant animals was accompanied by a reduced pressor response. Contractility to phenylephrine hydrochloride and norepinephrine was reduced in aortic rings isolated from pregnant, compared with nonpregnant, guinea pigs. Treatment with meclofenamate, a prostaglandin synthesis inhibitor, did not restore vasoreactivity in either the pregnant animal or the isolated vessel to levels observed in the nonpregnant state. We concluded that pregnancy reduced systemic vascular resistance and vasoreactivity but that mechanisms other than increased vasodilator prostaglandin production were likely responsible. PMID- 2912091 TI - Antibiotics in treatment of chorioamnionitis. PMID- 2912092 TI - The oral glucose tolerance test with one abnormal value. PMID- 2912093 TI - Management of pregnancy in diethylstilbestrol-exposed patients. PMID- 2912094 TI - Effects of progestins on estrogen-induced lipoprotein changes. PMID- 2912095 TI - Maternal temperature during labor. PMID- 2912096 TI - Second-assessment procedure for ovarian epithelial carcinoma. PMID- 2912097 TI - Mixed cord compression. PMID- 2912098 TI - Inactivation of prostaglandins in human decidua vera (parietalis) tissue: substrate specificity of prostaglandin dehydrogenase. AB - Prostaglandin dehydrogenase catalyzes the initial reaction in the inactivation of prostaglandin E2 and F2 alpha. To address the potential importance of this enzyme in regulating the tissue levels of active prostaglandins, we evaluated the kinetic properties of prostaglandin dehydrogenase in uterine decidua vera tissue of women. Specifically, we characterized the enzyme activity under optimal in vitro conditions in cytosolic fractions of uterine decidua vera tissue obtained at term and compared the substrate and cosubstrate specificities of prostaglandin dehydrogenase in cytosolic fractions of decidual tissues. The incubation conditions were optimized with either prostaglandin E2 or F2 alpha and nicotinamide-adenine dinucleotide or nicotinamide-adenine dinucleotide phosphate as substrates to ensure linearity of product formation with time of incubation and protein concentration. The apparent Michaelis-Menten constant of nicotinamide adenine dinucleotide-dependent prostaglandin dehydrogenase for prostaglandin E2 was 5.5 mumol/L. The apparent Michaelis-Menten constant of nicotinamide-adenine dinucleotide phosphate-dependent prostaglandin dehydrogenase for prostaglandin F2 alpha was 15 mumol/L. Prostaglandin E2 serves as a better substrate for prostaglandin dehydrogenase than does prostaglandin F2 alpha, irrespective of the cosubstrate. In cytosolic fractions of decidual tissues, the specific activity (apparent Vmax) of nicotinamide-adenine dinucleotide-dependent prostaglandin dehydrogenase was greater than that of nicotinamide-adenine dinucleotide phosphate-dependent prostaglandin dehydrogenase. In addition, we found that in decidual tissue obtained before or after the onset of labor, the specific activity of prostaglandin dehydrogenase varied widely. In tissues obtained after delivery by cesarean section, no significant differences were apparent in the specific activity of the enzyme before (9.3 to 125.8 nmol/min/mg protein) and after (27.8 to 103.4 nmol/min/mg protein) the onset of labor. In cytosolic fractions of decidual tissue obtained after vaginal delivery, the specific activity of nicotinamide-adenine dinucleotide-dependent prostaglandin dehydrogenase ranged from undetectable levels to 38.4 nmol/min/mg protein. We speculate that nicotinamide-adenine dinucleotide-dependent prostaglandin dehydrogenase in decidua serves to regulate the levels of bioactive prostaglandins in decidua vera tissue and the amounts of prostaglandins (and metabolites) produced in decidua or fetal membranes that reach myometrium and fetal membranes and enter maternal blood and amniotic fluid. PMID- 2912099 TI - Antepartum improvement of abnormal umbilical artery velocimetry: does it occur? AB - Absence of end-diastolic velocity on umbilical artery velocimetry suggests extreme elevation of placental vascular resistance and is associated with adverse pregnancy outcome. This study was undertaken to assess whether antepartum improvement of abnormal umbilical artery waveforms occurs. Thirty-one fetuses identified with absence of end-diastolic velocity between July 1985 and December 1987 at Women's Hospital underwent sequential umbilical artery velocimetry at 1- to 3-day intervals. The presence of end-diastolic velocity on subsequent scans was considered an improvement in waveforms. The mean diagnosis-to-delivery interval (20.5 +/- 4 days), gestational age at delivery (32.5 +/- 1.2 weeks), and birth weight (1440 +/- 210 gm) were significantly higher in five fetuses that showed improvement in waveforms, compared with the 26 fetuses that did not show improvement in waveforms (9.5 +/- 3.5 days, 29.5 +/- 0.9 weeks, and 940 +/- 70 gm, respectively). Ten perinatal deaths occurred, for a perinatal mortality rate of 32.3%. There was significant perinatal morbidity in the overall group as judged by intrauterine growth retardation, meconium, 5-minute Apgar scores less than 7, and cesarean section for fetal distress. We conclude that although absence of end-diastolic velocity is associated with adverse pregnancy outcome, antepartum improvement in umbilical artery waveforms occurred in 15% of the fetuses studied and was associated with an improvement in perinatal outcome. Factors that influenced this improvement, though unclear, might be related to maternal bed rest or medication and require further investigation. PMID- 2912100 TI - Effect of ovarian endometriosis on ovulation in rabbits. AB - To study the relationship between endometriosis and ovulatory dysfunction, we induced ovarian endometriosis in the rabbit model Adipose tissue was placed in the contralateral ovary as a control. Ovulation was induced with human chorionic gonadotropin, and ovulation points were counted before and after induction of endometriosis. Periovarian adhesions were graded, and ovaries were histologically examined. A significant decrease in the number of ovulation points was observed in ovaries with endometrial tissue (p = 0.001) but not in ovaries that contained adipose tissue (p = 0.095). Periovarian adhesions decreased the number of ovulation points (p less than 0.01) in ovaries that contained adipose or endometrial tissues. Multivariate analysis demonstrated that an increase in adhesion severity was correlated with a decrease in the number of ovulation points (p less than 0.05), but endometrial tissue was not (p = 0.45). We conclude that, in the rabbit model, minimal ovarian endometriosis impairs ovulation primarily through a mechanism related to periovarian adhesions. PMID- 2912101 TI - Progesterone antagonist (RU 486) for cervical dilation, labor induction, and delivery in monkeys: effectiveness in combination with oxytocin. AB - A progesterone antagonist (RU 486), combined with oxytocin, was effective in achieving cervical dilation, labor induction, and early delivery in near-term monkeys. Effects of RU 486 included accelerated flow of colostrum and transiently enhanced weight gain in infants. No overt toxicity on fetuses, mothers, or newborns was detected with the use of a single oral dose of 25 mg. PMID- 2912102 TI - Vascular catecholamine sensitivity during pregnancy in the ewe. AB - Four pregnant and four castrated ewes were chronically instrumented for the measurement of external iliac blood flow to test the hypothesis that pregnancy alters alpha-adrenergic sensitivity in a major regional circulation. Complete dose-response curves were generated to methoxamine, phenylephrine, and norepinephrine. Pregnancy was associated with no change in methoxamine sensitivity, an increase in phenylephrine sensitivity, and a decrease in norepinephrine sensitivity. These differential changes in drug sensitivity suggest (1) the alpha 1-receptor population is functionally similar between the two groups of animals, (2) uptake 1 is inhibited, and (3) either catechol-O methyltransferase activity is increased or the alpha 2- or beta-receptor population changes in this circulation during pregnancy. These data illustrate the complexity of the change in the adrenergic system during pregnancy. PMID- 2912103 TI - Surrogacy and Shakespeare: the Merchant's contract revisited. AB - Despite measures intended to assure that adequate information, reasonable understanding, and willing participation are involved in surrogacy contracts, questions of economic coercion remain for surrogate mothers. Surrogate contracts have been voided in several states. Nevertheless, obstetricians may be caught between their wish to help the infertile couple desirous of a baby through surrogacy and the ethical and legal questions about the use of surrogacy as a medical treatment. Obstetricians should not be placed in the position of Portia in The Merchant of Venice, that of an arbiter of an unethical contract. Obstetricians should not prescribe or acknowledge surrogacy as a medical treatment and should not knowingly participate in contracts that lead to surrogate pregnancy. PMID- 2912105 TI - Cesarean section: the House of Horne revisited. AB - In 1983, obstetricians from Dublin, Ireland, alleged that the perinatal mortality rate in the United States could be achieved with a cesarean section rate of approximately 5%. We responded in 1985 that population and infant outcome differences precluded such a low rate of cesarean sections at Parkland Memorial Hospital. The Dublin obstetricians responded 3 years later that it was unfair to compare obstetric services for only 1 year (1983). We respond again. PMID- 2912104 TI - Thyrotoxicosis complicating pregnancy. AB - During the 12-year period from 1974 through 1985, nearly 120,000 women were delivered of infants at Parkland Hospital, and pregnancy was complicated by overt thyrotoxicosis in 60 of them (1:2000). Initial treatment was based on clinical assessment, and propylthiouracil was usually given in doses of 300 to 800 mg daily. In compliant women seen by midpregnancy, euthyroidism was achieved by a mean of 8 weeks; however, the daily dose was decreased to less than or equal to 150 mg by delivery in only 10%. Metabolic status at delivery correlated directly with pregnancy outcome, and women treated earlier in pregnancy were more likely to be euthyroid at delivery and to have good outcomes. Diagnosis of thyrotoxicosis antecedent to pregnancy was associated with earlier treatment, and 80% of 28 such women were euthyroid by delivery. Conversely, 32 women with a first diagnosis during pregnancy had the preponderance of morbidity, including five of six stillbirths and six of seven cases of heart failure. This group was characterized by a relative delay in gestational age at diagnosis. Preterm delivery, perinatal mortality, and maternal heart failure were more common in women who remained thyrotoxic despite treatment and in those who were never treated. Although we infrequently achieved maintenance doses recommended by most, because there were minimal adverse effects from therapy described here and because uncontrolled thyrotoxicosis caused significant maternal and perinatal morbidity, aggressive medical therapy seems appropriate, especially when pregnancy is advanced. PMID- 2912106 TI - Respiratory failure in asthma during the third trimester: report of two cases. AB - We are reporting the cases of two pregnant women with life-threatening asthma, who required mechanical ventilation of the lungs and later were delivered of healthy infants. Maintenance of an adequate PaO2 is essential in such cases. To accepted asthma therapy, we added a warm metaproterenol-saline solution irrigation and suction, which functions like bronchoalveolar lavage to facilitate recovery. PMID- 2912107 TI - Gynecologic screening examinations: does the obstetrician-gynecologist's spouse comply? AB - The practicing obstetrician-gynecologist has certainly moved toward more active teaching and encouragement of preventive medical measures during the past decade. The purpose of this study was to determine how these measures espoused by the practitioner are applied in the physician's family setting. To accomplish this, 5000 questionnaires were sent to actively practicing obstetrician-gynecologists. Questions pertained to health habits as well as social and demographic issues. The results revealed that preventive medical practices, which have a high impact on morbidity and mortality, were not practiced to a significant degree by the spouses of obstetrician-gynecologists. Approximately 17% of the spouses did not have yearly Papanicolaou smears. Women older than 55 years of age were less likely to have this screening test than their younger cohorts. Only 65% perform breast self-examination, and 36% did not have screening mammography performed when recommended. In the postmenopausal group, 57% of the spouses did not receive estrogen replacement therapy, whereas 32% had both estrogen- and progesterone replacement therapy and 11% took estrogen alone. Contraceptive measures used by respondents indicated essentially equal distribution among methods available. The majority of the physicians who responded indicated they did not smoke (84%), did not use illegal drugs (99%), and used alcohol occasionally or not at all (71%). PMID- 2912108 TI - Gravidic macromastia: case report. AB - Gravidic macromastia is a rare condition. Breast enlargement in pregnancy is influenced by several hormones, including ovarian steroids and somatotropic or lactogenic polypeptide hormone. Evaluation showed minimal reactive stromal and periductal fibrosis. The treatment is surgical. PMID- 2912109 TI - Recurrent thromboembolism in pregnancy and puerperium. Is there a need for thromboprophylaxis? AB - By sending a questionnaire (response rate 93%) to 321 women with a history of venous thromboembolism and previous coagulation tests, 72 patients were identified who had a total of 87 pregnancies after the thromboembolic episode. The main aim of the study was to analyze the influence of prophylaxis during pregnancy and delivery on the development of further thromboembolic complications. During pregnancy there was no difference in frequency of thromboses between the group given prophylaxis (n = 20) and the group not receiving it (n = 67). At delivery the frequency of thrombosis was 5.3% among the 57 women given prophylaxis and 11.1% among the 30 without prophylaxis, a difference that is not significant. The implication of these findings is discussed both concerning the indications for giving prophylaxis and concerning the problem of designing relevant prophylactic trials. PMID- 2912110 TI - Trabecular repopulation by anterior trabecular meshwork cells after laser trabeculoplasty. AB - To study further the transient increase in trabecular cell division within the first two days after laser trabeculoplasty in human corneoscleral explant organ cultures, we used a pulse-chase protocol in which immediately after laser treatment 3H-thymidine was added to the culture medium for 48 hours (the pulse period). Fresh medium without radiolabel was then added for variable times (the chase period) before termination of the experiment. Autoradiography was used to follow changes in the regional distribution of the cells that divided during the pulse period and had 3H-thymidine-labeled DNA. Laser-treated explants, evaluated after a pulse with no chase, showed a fourfold increase in cell division (P less than .001) over nontreated controls. Nearly 60% of this cell division was localized to the anterior, nonfiltering region of the trabecular meshwork where it inserts into the cornea beneath Schwalbe's line. Trabecular cell division in other regions of the meshwork was not increased over controls at this time. After seven or 14 days of chase without radiolabel, the regional distribution of radiolabeled cells changed in laser-treated explants but not in controls. By 14 days, only 26% of the labeled cells remained in this anterior insert region, while 60% were found in the region of the burn sites. Macroautoradiography of whole explants corroborated these observations. Our data support the hypothesis that laser trabeculoplasty causes early cell division by a population of cells in the anterior meshwork; these new cells then migrate and repopulate the burn sites over the next few weeks. PMID- 2912111 TI - Intraocular pressure after cardiopulmonary bypass surgery. AB - The ocular effects of cardiopulmonary bypass surgery were prospectively studied in 46 patients. We examined preoperative and post-operative visual acuity, intraocular pressure, body weight, fluids infused during surgery, hematocrit, and cardiopulmonary bypass time. On the first postoperative day mean intraocular pressure increased 2.1 mm Hg (P = .003) from baseline preoperative levels. Over the first postoperative day intraocular pressure increased in 29 (63%) of the patients. Three patients (7%) had a greater than 10 mm Hg rise. The mean intraocular pressure returned to baseline by the third postoperative day. Patient weight increased from preoperative levels an average of 9.3 lbs (P less than .0001) on day 1 and 6.5 lbs on day 3. Mean hematocrit decreased 11.3% (P less than .0001) on day 1 from baseline and remained at that level through day 3. None of the patients complained of visual dysfunction during the course of this study and none showed more than a two-line decrease in near visual acuity. The increase in intraocular pressure did not correlate with the postoperative weight gain or hemodilution. However, the medications necessary after cardiac surgery may be a significant confounding variable. This study demonstrates that one cause of ocular problems from cardiopulmonary bypass surgery may be related to the dynamics of intraocular pressure. PMID- 2912112 TI - Intractable diplopia after vision restoration in unilateral cataract. AB - Twenty-four patients lost their ability to fuse when their binocular function was disrupted for at least 2 1/2 years by a unilateral traumatic cataract or a unilateral traumatic cataract followed by uncorrected aphakia. Three patients were 6 years old, one was 8 years old, and the remaining 20 patients were aged 10 years or older at the time of the injury. All patients had intractable diplopia when the cataract was removed and the aphakia corrected. Aniseikonia was not the cause of this inability to fuse and the insertion of an intraocular lens provided no relief. The prognosis for the elimination of diplopia, other than by occlusion of one eye, was poor. PMID- 2912113 TI - Nd:YAG laser photodisruption of hemorrhagic detachment of the internal limiting membrane. AB - We used a Q-switched Nd:YAG laser to create an opening in the internal limiting membrane in three eyes with hemorrhagic detachment of the internal limiting membrane. In all instances, after membranotomy blood was rapidly cleared from the preretinal space resulting in prompt improvement in visual acuity. No retinal injury was observed. Nd:YAG laser photodisruption may be useful in the treatment of some cases of subinternal limiting hemorrhages. PMID- 2912114 TI - Subretinal hemorrhage in atrophic age-related macular degeneration. AB - In eight eyes of eight patients we retrospectively studied the outcome of subretinal hemorrhage occurring in areas of atrophy of retinal pigment epithelium and choriocapillaris secondary to age-related macular degeneration. These patients were followed up for one to 20 months after the initial appearance of the hemorrhage. No subretinal new vessels were associated with these hemorrhages, which resolved over one to 15 months. Our findings indicated that hemorrhages occurring within areas of atrophy are not necessarily associated with subretinal new vessels, and that this type of hemorrhage has a good prognosis for resolution. PMID- 2912115 TI - Irregular astigmatism after radial and astigmatic keratotomy. AB - Eleven eyes of six patients, who had been referred for management of irregular astigmatism after receiving crossed incisions for myopic astigmatism, had moderate to marked irregular corneal astigmatism with marked flattening in the meridians of intersecting incisions. All six patients had a decrease in best corrected visual acuity with spectacles after surgery. Visual acuity with spectacles was 20/40 in five of 11 eyes; with contact lenses it reached 20/40 in ten of 11 eyes. However, two patients could not wear the contact lenses because of lens decentration caused by the marked distortion in corneal topography. Even with contact lenses, visual acuity could only be improved to 20/25 or better in six of 11 eyes. PMID- 2912116 TI - Edema of the corneal stroma induced by cold in trigeminal neuropathy. AB - A patient with a left sensorimotor trigeminal neuropathy was found to have edema of the corneal stroma induced by cold. Examination at room temperature demonstrated an anesthetic left cornea with minimal injection of the left eye and multiple punctate epithelial erosions. Corneal thickness, mean endothelial cell size, coefficient of variation of cell size, endothelial permeability to fluorescein, and aqueous humor flow rate, measured at room temperature were similar in the two eyes. After 47 minutes in a cold room at 4 C, the corneal thickness in the left eye increased from 0.55 to 0.65 mm, whereas that of the right eye remained at 0.55 mm. During the period of maximum swelling, the left cornea had clinical stromal edema with folds in Descemet's membrane but no epithelial edema. After return to room temperature there was a gradual return to normal corneal thickness over three hours. Fluorophotometry showed no evidence of increased endothelial permeability during corneal swelling in the left eye. Specular microscopy after 15 minutes of cold exposure demonstrated many swollen and irregular endothelial cells with darkened areas between cells in the left eye. Sensory nerve deficiency in the human cornea can produce an abnormal sensitivity to cold, resulting in defective control of corneal hydration. This study suggests that this effect may be on the endothelium. PMID- 2912117 TI - Rapid streptococcal antigen detection in experimental keratitis. AB - We assessed the role of commercially available immunodiagnostic procedures in comparison to Gram stain and culture in experimental bacterial keratitis. Rabbit corneas were inoculated with Streptococcus pneumoniae, S. pyogenes, S. faecalis, or Haemophilus influenzae. Corneal scrapings were processed before and during antibacterial therapy using a coagglutination assay to detect pneumococcal capsular antigen (Phadebact Pneumococcus test) and an enzyme immunoassay to detect group A streptococcal cell-wall antigen (TestPack Strep A test). In untreated infected eyes, both immunoassays were highly specific and as sensitive as Gram stain for detection of the respective microorganisms. For S. pneumoniae keratitis, the sensitivity of coagglutination was 82% and Gram stain, 73%. For S. pyogenes keratitis, the sensitivity of enzyme immunoassay was 100% and Gram stain, 62%. Immunoassays and Gram stain were less sensitive than culture during antibacterial therapy. Successful clinical application of the coagglutination assay in a patient with pneumococcal keratitis permitted early use of specific cephalosporin treatment. PMID- 2912118 TI - DNA cell cycle studies in uveal melanoma. AB - We histologically studied uveal melanomas treated with surgery only (enucleation or ciliochoroidectomy), low-dose (20 Gy) preenucleation radiation followed by enucleation, or enucleated melanomas after high-dose (50 to 80 Gy) charged particle beam therapy. There was significantly less bromodeoxyuridine uptake in irradiated vs nonradiated melanomas (P less than .0001). Similarly, tissue culture growth of irradiated tumors was significantly less (P less than .007). These data demonstrate destruction of reproductive integrity of helium ion irradiated melanomas. The incorporation of bromodeoxyuridine and fine needle aspiration biopsy techniques may be useful in the delineation of successfully irradiated tumors from tumors with apparent growth secondary to radiation vasculopathy. PMID- 2912119 TI - Effects of carbachol and acetylcholine on intraocular pressure after cataract extraction. AB - We compared the effect of carbachol and acetylcholine on intraocular pressure 24 hours after extracapsular cataract extraction. All agents were administered intracamerally at the time of surgery. Sixty patients scheduled for routine extracapsular cataract extraction and intraocular lens implantation were randomly assigned into one of three treatment groups: (1) carbachol, (2) acetylcholine, or (3) 0.5% balanced salt solution (placebo). Baseline intraocular pressures were determined the day before surgery, and postoperative pressures were measured approximately 24 hours after surgery. The group intraocular pressures averaged over preoperative and postoperative values were 21.06 mm Hg in the acetylcholine group, 19.36 mm Hg in the control group, and 17.30 mm Hg in the carbachol group. The average difference between preoperative and postoperative intraocular pressure measurements for the three groups were 7.33 mm Hg for the acetylcholine group, 8.73 mm Hg for the control group, and 2.20 mm Hg for the carbachol group. Only carbachol was significantly different from placebo on statistical subsequent testing. Carbachol is suggested as the agent of choice both for achieving intrasurgical miosis and prophylaxis of increasing intraocular pressure after cataract surgery. PMID- 2912120 TI - Contralateral trochlear nerve paresis and ipsilateral Horner's syndrome. AB - Two patients had paresis of the trochlear nerve contralateral to the site of lesions in the brainstem. Both patients had ipsilateral blepharoptosis and miosis suggesting oculosympathetic paresis from involvement of the descending sympathetic tract, adjacent to the fourth cranial nerve nucleus and its fascicles, in the caudal mesencephalon. Cerebral antiography documented an arteriovenous malformation of the brainstem in Case 1. Magnetic resonance imaging disclosed a lesion of high signal intensity on T2-weighted images involving the dorsal mesencephalon in Case 2. Involvement of the superior cerebellar peduncle produced ipsilateral dysmetria and ataxia. Lesions involving the fourth cranial nerve nucleus or its fascicles, before decussation in the superior medullary velum, and adjacent sympathetic fibers may produce an ipsilateral Horner's syndrome and contralateral superior oblique muscle paresis. PMID- 2912121 TI - The expanding ophthalmologic spectrum of Lyme disease. PMID- 2912122 TI - Pseudotumor cerebri syndrome associated with Lyme disease. PMID- 2912123 TI - Magnetic resonance imaging of retrobulbar changes in optic nerve position with eye movement. PMID- 2912124 TI - Discordance of accommodative esotropia in monozygotic twins. PMID- 2912125 TI - Sudden unilateral visual loss after autologous fat injection into the glabellar area. PMID- 2912126 TI - Staphylococcus aureus conjunctivitis and sepsis in a neutropenic patient. PMID- 2912127 TI - Iridoschisis associated with syphilitic interstitial keratitis. PMID- 2912128 TI - Ocular myasthenia gravis associated with autoimmune hemolytic anemia and Hashimoto's thyroiditis. PMID- 2912129 TI - Nasolacrimal drainage system obstruction after orbital decompression. PMID- 2912130 TI - Modulation of angiotensin II binding sites in neuronal cultures by mineralocorticoids. AB - Previous studies have determined that mineralocorticoid hormones are able to increase the number of angiotensin II (ANG II)-specific binding sites in rat diencephalon and in neuronal cultures and also increase the drinking response elicited by centrally injected ANG II. In the present study, we have examined the specificity and mechanisms of this mineralocorticoid action. In neuronal cultures from the hypothalamus and brain stem (H/BS), both D-aldosterone and deoxycorticosterone acetate (DOCA) caused significant time- and dose-dependent increases in 125I-labeled ANG II-specific binding. This effect was not mimicked by the synthetic glucocorticoid dexamethasone, or by testosterone, beta-estradiol or progesterone. However, the steroid corticosterone induced a moderate increase in [125I] ANG II binding. This may have occurred as a result of its high affinity for the mineralocorticoid type I receptor. DOCA was ineffective in increasing [125I]ANG II specific binding both in neuronal cultures prepared from the cerebellum and in pure astrocytic glial cultures, indicating that this mineralocorticoid effect is specific both for neurons and for certain brain regions. The increase in [125I]ANG II-specific binding elicited by DOCA was abolished by cotreatment with the mineralocorticoid receptor blockers mespirenone or ZK97894 and by cotreatment with cycloheximide. Taken together, these observations suggest that the mineralocorticoid-induced increase in [125I]ANG II specific binding in H/BS neuronal cultures is a specific event, which is mediated via mineralocorticoid type I receptors and which requires protein synthesis. PMID- 2912131 TI - Improved propagation in myometrium associated with gap junctions during parturition. AB - The hypothesis that gap junction (GJ) formation between myometrial cells at term improves electrical coupling was tested. We measured the spread of electrical excitation from six extracellular electrodes aligned on uterine strips in either the longitudinal (axial) or transverse (circumferential) direction. Spontaneous bursts propagated over the entire 15-mm recording distance in the axial direction at both preterm and parturition and showed some characteristics of a system of coupled relaxation oscillators. However, individual spikes within the bursts propagated further and with higher velocity at parturition than at preterm. In the circumferential direction, both bursts and individual spikes propagated further at parturition than before. Propagation in this axis at parturition appeared to require an intact circular muscle layer. Spikes evoked by electrical stimulation also propagated further and with higher velocity in both axes at parturition. Electron microscopy showed many GJs between uterine smooth muscle cells during parturition, but few and sometimes no GJs at preterm. Thus improved propagation was associated with increased GJ contact between myometrial cells, consistent with the hypothesis that gap junction formation at term improves electrical coupling. PMID- 2912132 TI - Relationship between cytosolic free Ca2+ and Na+-Ca2+ exchange in aortic muscle cells. AB - We examined the relationship between extracellular Na+ ([Na+]o) and cytosolic free Ca2+ ([Ca2+]i) in primary and passaged cultures of aortic muscle cells. Removing [Na+]o increased [Ca2+]i by approximately 10-fold in cells that were Na+ loaded. Decreasing [Na+]o from 140 to 32 mM caused the half-maximal increase in [Ca2+]i. [Ca2+]i exhibited a sigmoidal dependence on [Na+]o. Mg2+, a competitive inhibitor of Na2+-Ca2+ antiport in these cells, antagonized the increase in [Ca2+]i produced by lowering [Na+]o. High K+ decreased the potency of Mg2+ 6.5 fold as previously reported for Na+ gradient-dependent 45Ca2+ influx. In contrast to the Na+-loaded cells, removing [Na+]o caused no detectable change in [Ca2+]i in cells with normal Na+ even though the calculated electrochemical driving force for Na+-Ca2+ exchange was large enough to almost maximally increase [Ca2+]i in the Na+-loaded cells. We conclude that Na+-Ca2+ antiport activity is latent in the unstimulated cell at basal intracellular Na+ and Ca2+. PMID- 2912133 TI - Metabolic alterations induced in cultured skeletal muscle by stretch-relaxation activity. AB - Avian pectoralis muscle cells differentiated in vitro are mechanically stimulated by repetitive stretch-relaxations of the cell's substratum. Their metabolic response to mechanical activity is determined by measuring rates of [3H]deoxy-D glucose uptake and lactate efflux. These two metabolic parameters show a similar biphasic response to mechanical stimulation. During the first 4-6 h of activity, [3H]deoxy-D-glucose uptake and lactate efflux increase 34 and 26%, respectively; at 8 and 24 h of activity, [3H]deoxy-D-glucose uptake and lactate efflux are no longer elevated relative to control values. With continued activity beyond 24 h, their rates are again significantly elevated (150 and 93% by 48 h, respectively). The long-term increases in [3H]deoxy-D-glucose uptake and lactate efflux occur independently of medium growth factors. Protein synthesis is required for the short-term increase in [3H]deoxy-D-glucose uptake, but muscle electrical activity is not required for either short- or long-term increases in [3H]deoxy-D-glucose uptake because both occur in the presence of tetrodotoxin. This new model system allows for the analysis of mechanically induced metabolic alterations in aneural skeletal muscle cells under the defined conditions of tissue culture. PMID- 2912134 TI - Temperature-controlled perfusion apparatus for microscope using transparent conducting film heater. AB - We describe a novel temperature-controlled perfusion apparatus for electrophysiological studies on isolated cells or membrane patches. The apparatus uses a transparent conducting film of indium-tin-oxide as a heating element. The film heater deposited on a glass sheet allows us to construct a structurally simple apparatus that is able not only to heat directly the bath chamber but also to preheat the perfusion solution on the stage of an inverted microscope. The structure ensures a uniform temperature in a bath chamber that has a working area of approximately 6 X 12 mm2 and a capacity of 1 ml. A control unit, designed for operation of the apparatus, regulates the temperature of the bathing solution without introducing electrical noise in a range from ambient temperature to greater than 37 degrees C with an accuracy within +/- 1 degree C. The apparatus is 12 mm in height and designed to fit on the stage of a standard inverted microscope. Since the bath chamber for perfusion experiments is readily interchanged with others, the apparatus can be used widely in microscopic studies of various cells in static solutions. PMID- 2912135 TI - Response of aequorin-loaded platelets to activators of protein kinase C. AB - The protein kinase C activators phorbol ester 12-myristate 13-acetate (PMA) and 1 oleyl-2-acetylglycerol (DAG) cause platelet aggregation, secretion, and a rise in aequorin-indicated cytoplasmic Ca2+ ([Ca2+]i), but the importance of this action to platelet activation by these agonists has not been established. We found that the previous addition of PMA or DAG either enhanced or inhibited the platelet response if thrombin was subsequently added, depending on the latter's concentration. The effects of PMA or DAG on the response to thrombin were obtained only if the agonists were added in concentrations sufficient to elevate [Ca2+]i themselves. A [Ca2+]i rise also occurred after the second agonist (thrombin), but its magnitude did not necessarily correlate with subsequent aggregation, secretion, or the activation of protein kinase C as reported by the phosphorylation of a 47-kDa protein (p47). The protein kinase C inhibitor sphingosine inhibited aggregation and p47 phosphorylation caused by PMA or DAG alone or with thrombin, but the [Ca2+]i rise in response to the first agonist was not affected. PMA-induced aggregation and p47 phosphorylation were inhibited by quin2, which also inhibited protein kinase C activity in a cell-free system. We conclude that a rise in aequorin-indicated [Ca2+]i is necessary for PMA or DAG to activate platelets or to alter the subsequent platelet response to thrombin; this [Ca2+]i rise may be a prerequisite for activation of protein kinase C. PMID- 2912136 TI - Electrogenic Na+-ascorbate cotransport in cultured bovine pigmented ciliary epithelial cells. AB - The high level of ascorbic acid (AA) in the aqueous humor of many mammals suggests an active transport of AA across the double-layered ciliary epithelium from blood to aqueous humor. We used [14C]AA to study AA uptake in bovine pigmented ciliary epithelial cells in tissue culture. We observed a 40-fold intracellular accumulation of AA, which was dependent on extracellular Na+. With labeled dehydroascorbate (DHA, the oxidized form of the vitamin) in the medium, there was a 20-fold intracellular accumulation of the label. However, the time course of DHA uptake was different compared with AA uptake and was not Na+ dependent, suggesting different transport systems for AA and DHA. AA uptake was inhibited by 1 mM phloretin and in the presence of isoascorbate. Furthermore, AA uptake was markedly reduced when intracellular Na+ was elevated by preincubation with ouabain or amphotericin B. With increasing AA concentration, Na+-dependent AA uptake exhibited first-order saturation kinetics with half-maximal uptake at 76 microM AA. Na+ dependence of AA uptake revealed a sigmoidal curve of Na+ dependent AA uptake vs. Na+ concentration with a half-maximal AA uptake at 45.4 mM Na+. The slope of the Hill plot from these data was 1.94, suggesting a transport system translocating two or more Na+ for one AA. This stoichiometry implies electrogenicity of the transporter. We, therefore, measured membrane potentials using conventional microelectrodes. Addition of 200 microM AA resulted in a depolarization of the membrane voltage by 4.9 +/- 0.5 mV (n = 22), which was absent in Na+ free medium and was markedly reduced by phloretin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2912137 TI - Capillary and size interrelationships in developing rat diaphragm, EDL, and soleus muscle fiber types. AB - The effects of maturation on the interrelationship between skeletal muscle fiber area and capillarization was investigated in specific fiber types (I, IIa, IIb, IIc) of male Wistar rats at seven developmental periods ranging from 8 to 85 days postnatal. Fiber type specific developmental properties were compared in three different muscles, the diaphragm (DIA), extensor digitorum longus (EDL), and soleus (SOL), which are known to differ widely in function. All fiber types in each of the three muscles examined exhibited large increases in area (FA), the magnitude and time course of the increase being related to both the type of fiber and the muscle in which the fiber was located. For type I fibers, areas increased from 3- to 18-fold (SOL greater than EDL greater than DIA), whereas in type IIa fibers, area increased ranged between 5- to 11-fold (SOL greater than EDL greater than DIA). Growth rates in IIb fibers were more homogeneous between muscles ranging from 11- to 14-fold. Capillarization, as indicated by the capillary contacts per fiber (CC), increased in all fiber types regardless of muscle origin. These increases ranged between 1.7- and 2.2-fold for type I fibers, between 2.4- and 2.5-fold for type IIa fibers, and between 2.0- and 3.0-fold for type IIb fibers. In general, capillary density expressed as the ratio of the number of capillary contacts divided by the fiber area (CC/FA) progressively declined in all fiber types with age. The rate of the decline in CC/FA was mediated in large part by the changes in fiber area.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2912138 TI - Inhibition of colonic Na+ transport by amiloride analogues. AB - The potency of several amiloride analogues to inhibit electrogenic Na+ transport in colon from dexamethasone-treated rats was compared. Short-circuit current (Isc) across the colonic mucosa and 22Na+ uptake into membrane vesicles derived from colonic enterocytes was determined in dexamethasone-treated rats. Kinetic analysis of inhibition of Isc and 22Na+ uptake revealed the presence of a high- and low-affinity amiloride pathway. One pathway had a high affinity [(Ki-Isc; Ki uptake] to benzamil (15.5 nM; 5.4 nM), phenamil (19.4 nM; 7.0 nM), 3',4' dichlorobenzamil (29.0 nM; 25.2 nM), and amiloride (115 nM; 12.4 nM) but a much lower affinity to 5-(N-ethyl-N-isopropyl)amiloride (EIPA) (greater than 100 microM; greater than 9.9 microM) and 5-(N-propyl-N-butyl)-2'-4'-dichlorobenzamil (PBDCB) (greater than microM; greater than 32.8 microM). The high-affinity pathway accounted for 75-83% of the transport of Na+. The second pathway had nearly the same low affinity for each of the analogues (e.g., amiloride Ki-Isc 1 microM; Ki uptake 4 microM) and accounted for only 15-25% of the transport of Na+. The results demonstrate that the structure-inhibitory pattern of these amiloride analogues for the high-affinity pathway is the pattern observed in other electrogenic Na+-transporting epithelia and that this pharmacological profile is preserved in membrane vesicles derived from colonic enterocytes. In addition, the potency of EIPA and benzamil to inhibit electroneutral Na+ transport across the colon from normal rats (i.e., not treated with dexamethasone) was also investigated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2912139 TI - Volume-sensitive, Cl-dependent K transport in resealed human erythrocyte ghosts. AB - Potassium influx and efflux in Cl and NO3 media were measured in resealed ghosts prepared from human red cells. Cl-dependent K influx was three times that in intact cells and, as in intact cells, was partially supported by Br but not by thiocyanate (SCN). In other properties, this flux differed from that in intact cells: substitution of N-methylglucamine for Na did not decrease but rather increased Cl-dependent K influx, the affinity for external K was reduced, with a Km of 21.3 +/- 12.5 mM, and inhibition by furosemide and bumetanide was incomplete. Furosemide at 1 mM inhibited Cl-dependent influx by 26 and 51% at 4 and 20 mM K, respectively. Bumetanide inhibited Cl-dependent K influx by 0 and 55% at concentrations of 10 microM and 1 mM, respectively, in 4 mM K, with no further inhibition at 20 mM K. Neither the magnitude nor the properties of the flux were altered by preparing ghosts in the presence of 1,4-dithiothreitol, indicating that sulfhydryl oxidation was not responsible for the altered flux in ghosts. Treatment with N-ethylmaleimide (NEM) either before or after ghost preparation did not increase Cl-dependent K influx. However, Cl-dependent influx in ghosts could be augmented by increasing ghost volume or ATP content. Resealed human erythrocyte ghosts thus exhibit a volume- and ATP-sensitive, Cl-dependent K flux that differs substantially from the putative Na-K-Cl cotransport in intact cells in that it is independent of Na, is relatively resistant to furosemide and bumetanide, and has a low affinity for K.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2912140 TI - Ion microprobe analysis of mouse calvariae in vitro: evidence for a "bone membrane". AB - It is not clear whether the bone mineral is in passive physicochemical equilibrium with the extracellular fluid (ECF) or is separated from it by a metabolically active partition, a so-called "bone membrane." We used a sensitive high spatial resolution scanning ion microprobe utilizing secondary ion mass spectrometry to compare the relative concentrations of 23Na, 39K, and 40Ca on the surface, subsurface, and cross section of cultured live bone with the concentrations in similar regions of dead bone. Calvariae from neonatal mice were dissected and either incubated for 24 h (live) or subjected to 3 freeze-thaw cycles to kill the bone cells prior to incubation (dead). The live bone has abundant surface Na and K relative to Ca and the Na/K is approximately unity. With dead bone there is a dramatic fall in the K/Ca and an increase in the Na/K. These findings are most consistent with an egress of bone K after cell death. Flux measurements indicate a net influx of Ca into the dead bone. The marked change in relative ion concentrations with cell death indicates that live bone is not in passive physiochemical equilibrium with the surrounding medium. There appears to be a metabolically active partition, a so-called bone membrane, between the mineral and the culture medium that utilizes bone cells to maintain ion gradients. PMID- 2912141 TI - Regulation of branched-chain 2-oxo acid dehydrogenase activity during exercise. AB - The levels of the branched-chain amino and oxo acids were measured in muscle and plasma after exercise and 10 min postexercise. Leucine was increased in both muscle and plasma after exercise and 10 min postexercise. The muscle levels of the branched-chain oxo acids were not increased immediately after exercise but were increased 10 min postexercise. Exercise caused a large increase in the plasma levels of the oxo acids of leucine and isoleucine that was further increased 10 min postexercise. The activity of branched-chain 2-oxo acid dehydrogenase (BCOAD) was increased immediately after exercise but returned to the control value by 10 min postexercise. The lack of correlation between the muscle and plasma levels of the branched-chain amino and oxo acids and BCOAD activity suggests that these amino and oxo acids are not the primary physiological regulators of BCOAD activity during exercise. On the other hand, an excellent correlation was found between the muscle ATP level and BCOAD activity, with the ATP content decreasing in tandem with an increase in BCOAD activity during exercise and decreasing during the recovery period after exercise. PMID- 2912143 TI - Ca2+ concentration influences the hepatic extraction of bioactive human PTH-(1 34) in rats. AB - The regulation of bioactive human parathyroid hormone [hPTH-(1-34)] hepatic extraction was studied in vitro by means of an isolated rat liver perfusion system. A standard buffer containing 20% red blood cells, 2% albumin, and variable concentrations of hPTH-(1-34) and Ca2+ was used in nonrecirculation experiments. Hepatic blood flow was kept constant at approximately 1.8 ml.g liver 1.min-1. hPTH in portal and hepatic veins was measured by a radioimmunoassay specific for hPTH-(1-34), and the results obtained were validated by gel chromatography analysis of the hormone measured. Results are expressed as mean +/ SD of five to six different experiments. In normocalcemic conditions (Ca2+ approximately 1.2 mmol/l), the hepatic extraction ratio of hPTH remained stable at 0.357 +/- 0.011 and 0.370 +/- 0.010 for hPTH-(1-34) concentrations of 0.156 +/ 0.002 and 1.314 +/- 0.014 pmol/ml; it decreased to 0.145 +/- 0.013 (P less than 0.001) for a hPTH-(1-34) concentration of 5.817 +/- 0.167 pmol/ml. Kinetics analysis of the normocalcemic data disclosed a Vmax of 1.971 +/- 0.18 pmol.min 1.g liver-1 and a Km of 1.410 +/- 0.39 pmol/ml. When hPTH-(1-34) concentration was kept stable with varying Ca2+ concentrations, elevated (1.62 +/- 0.01 mmol/l) Ca2+ gave an hepatic extraction ratio similar to normocalcemic conditions (0.335 +/- 0.014 vs. 0.357 +/- 0.011 mmol/l), whereas it significantly decreased in hypocalcemia (0.78 +/- 0.01 mmol/l) to 0.219 +/- 0.014 mmol/l (P less than 0.001). Kinetics were similar to normocalcemic conditions when Ca2+ concentration was elevated but appeared modified by hypocalcemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2912142 TI - Effect of thyroid status on catecholamine stimulation of thyroxine 5'-deiodinase in brown adipocytes. AB - We examined type II 5'-iodothyronine deiodinase activation by adrenergic agonists in dispersed brown adipocytes from euthyroid and hypothyroid rats. In euthyroid cells, basal deiodinase activity was 30-100 fmol I-.h-1.10(6) cells-1 and increased four- to fivefold during exposure to norepinephrine, an effect that was enhanced by alprenolol. In cells from hypothyroid rats, norepinephrine caused a three- to fourfold greater deiodinase stimulation than occurred in euthyroid cells but alprenolol inhibited the response. In euthyroid cells, phenylephrine caused greater stimulation than did norepinephrine, but this was inhibited by alprenolol. Isoproterenol and 8-bromoadenosine 3',5'-cyclic monophosphate (8 BrcAMP) inhibited the phenylephrine response but were modestly stimulatory alone. Although both alpha 1- and beta-adrenergic agonists increased deiodinase activity modestly in hypothyroid cells, in combination they caused a marked synergistic stimulation. This synergism was induced by 8-BrcAMP and forskolin, as well as by isoproterenol. The stimulation of deiodinase in both cell types was due to an increase in Vmax without an alteration in the Km and required mRNA synthesis. The markedly greater deiodinase response of the hypothyroid brown adipocyte to catecholamines may serve to enhance the impaired thermogenic response of this tissue to cold exposure. PMID- 2912144 TI - Prostaglandins augment muscarinic responses in the rabbit cecum. AB - Effects of prostaglandin E2, F2 alpha, and synthetic thromboxane A2 (PGE2, PGF2 alpha, and STA2, respectively) on electrical and mechanical responses of the rabbit cecum were investigated. Transmural electrical stimulation evoked an excitatory junction potential (EJP) and contraction, events that were inhibited by 1 microM atropine or 0.3 microM tetrodotoxin. Indomethacin (up to 30 microM) modified neither the membrane potential nor the muscle tone but did inhibit amplitudes of the EJP and the twitch contraction. In the presence of 30 microM indomethacin, PGE2 (below 1 nM) had no effect on the membrane potential or muscle tone, while PGE2 (above 10 nM) contracted the cecal tissues, without depolarization. PGE2 enhanced the twitch contraction and restored the EJP in the presence of 30 microM indomethacin. Acetylcholine (0.1-3 microM) depolarized the membrane, but in the presence of 30 microM indomethacin, this depolarization was inhibited. PGE2 (0.1-100 nM) prevented these inhibitory actions of indomethacin. PGF2 alpha (0.1-100 nM) had weaker actions than PGE2 while STA2 (0.1-100 nM) had no effect on muscarinic responses. Thus muscarinic responses are augmented by primary prostaglandins. PMID- 2912145 TI - Sphincteric action of the diaphragm during a relaxed lower esophageal sphincter in humans. AB - We studied the effects of involuntary and voluntary contraction of the diaphragm on esophagogastric junction (EGJ) pressure during esophageal distension in healthy human volunteers. The EGJ pressure was monitored using a Dent sleeve device. Along with the pressure we concurrently monitored diaphragm electromyogram (EMG) using intra-esophageal bipolar electrodes that were placed on the nonpressure sensing surface of the sleeve device. Graded esophageal distensions were performed by graded inflations of a 2-cm-diameter balloon that was positioned 7 cm above the EGJ. The graded esophageal distensions caused a graded increase in the amplitude of lower esophageal sphincter (LES) relaxation (end-expiratory EGJ pressure). In a majority of the subjects, esophageal distension had no effect on spontaneous inspiratory EGJ pressure increase and diaphragm EMG. During sustained LES relaxation of greater than 70% induced by sustained esophageal distention, graded voluntary contractions of the diaphragm induced proportional increases in the EGJ pressure and diaphragm EMG. The EGJ pressure and diaphragm EMG were similar during diaphragmatic contraction both before and during esophageal distension. During a maximal and sustained diaphragm contraction, esophageal distension had no effect on the EGJ pressure. We conclude that there are two distinct sphincteric mechanisms at the EGJ, the LES and crural diaphragm, and they respond differently to distension of the distal esophagus. PMID- 2912146 TI - Saturated fatty acid diet prevents radiation-associated decline in intestinal uptake. AB - Adult female Sprague-Dawley rats were fed isocaloric semipurified diets containing a high content of either polyunsaturated (P) or saturated (S) fatty acids; these diets were nutritionally adequate, providing for all known essential nutrient requirements. On day 3 after beginning S or P, one group of animals was exposed to a single 6-Gy dose of abdominal radiation, and the other half was sham irradiated. S or P diets were continued for a further 14 days. Brush-border membrane purification and sucrase-specific activities were unaffected by diet or by abdominal irradiation. In rats fed P, irradiation was associated with an increase in jejunal brush-border membrane total phospholipid and the ratio of phospholipid to cholesterol; these changes were not observed in animals fed S. In irradiated rats, ileal brush-border membrane phospholipid per cholesterol was high in animals fed S compared with P. In irradiated animals fed P, there was reduced jejunal and ileal uptake of several medium- and long-chain saturated and unsaturated fatty acids and cholesterol, and the ileal uptake of higher concentrations of glucose was reduced in irradiated animals fed P. In contrast, lipid uptake was similar in control and irradiated animals fed S except for cholesterol uptake, which was reduced. Ileal uptake of higher concentrations of glucose was increased in irradiated animals fed S. Quantitative autoradiography failed to demonstrate any change in the distribution of leucine or lysine transport sites along the villus 1 or 2 wk after abdominal irradiation or in response to feeding S or P. Also, these differences in transport achieved by feeding S to radiated animals were not explained by variations in the animals' food consumption or intestinal mucosal surface area. Thus the use of short-term feeding with a saturated fatty acid diet in the prevention of acute irradiation damage to the intestine warrants further investigation in humans. PMID- 2912147 TI - Influence of distension on absorption and villous structure in rat jejunum. AB - In urethan-anesthetized rats the appearance rates of urea (U), antipyrine (A), and alpha-methyl-D-glucoside (MG) in the venous blood of perfused jejunal segment were measured in the undistended state and after elevation of the intraluminal pressure up to 10 cmH2O. Serosal and inner cylindrical surface area of the jejunal segment were enlarged by maximally 100 and 150%, respectively. The absorption rates, however, increased only by 34 (U), 28 (A), and 26% (MG). The increase of the supravillous diffusion resistance contributed only partially to this effect. The "cylindrical" permeability coefficient (Pcyl, average permeability coefficient related to inner cylindrical area, neglecting villous structure) decreased by 39, 57, and 50%, respectively. Due to circular stretching, broad intervillous spaces were formed that covered finally approximately 40% of the mucosal surface area. The additional intervillous diffusion resistance in these spaces was more effective than the absorption through the lateral surface of the villi. Thus the overall permeability of the mucosa, i.e., Pcyl, was reduced. Calculations based on a simplified model of the mucosa confirmed the experimental results. PMID- 2912149 TI - Central neurotensin affects rat gastric integrity, prostaglandin E2, and blood flow. AB - The aim of this study is to define the effect(s) of centrally administered neurotensin (NT) on gastric mucosal integrity, prostaglandin E2 (PGE2) generation, and blood flow during stress induced by cold-water restraint (CWR) in rats. Intracerebroventricular (icv) NT reduced macroscopic and microscopic damage. The former effect was dose dependent and was totally blocked by indomethacin pretreatment. Gastric mucosal PGE2 increased 27 and 30% at 30 and 60 min, respectively, in nonrestrained rats given icv NT. PGE2 generation was reduced in control rats during CWR but was maintained in CWR rats treated with icv NT. Gastric mucosal blood flow (GMBF) was significantly reduced in control rats during CWR. Mucosal blood flow was maintained at nonrestraint levels in the presence of icv NT during CWR; however, this effect was abolished by parenteral indomethacin pretreatment. Similarly, intravenous 16,16-dimethyl-PGE2 (200 micrograms.kg-1.h-1) maintained GMBF of non-CWR levels as well as preventing the macroscopic damage normally associated with CWR. These data suggest a protective role for central NT on the gastric mucosa, mediated, at least in part, by PGE2 generation and gastric mucosal blood flow. PMID- 2912148 TI - Relation between biliary glutathione excretion and bile acid-independent bile flow. AB - Glutathione efflux into bile of the fluorocarbon-perfused isolated rat liver was altered with eight different agents (L-buthionine-[S,R]-sulfoximine, cefamandole, sodium arsenite, phenobarbital, furosemide, nitrofurantoin, aminopyrine, and benzylamine), and correlations were established between bile flow and biliary excretion of 1) glutathione, 2) endogenous bile acids, and 3) glutathione plus bile acids. Biliary efflux of endogenous bile acids was relatively low (0.5-5 nmol.min-1.g liver-1) and was minimally affected by these agents. Biliary glutathione excretion in control livers was between 4 and 9 nmol.min-1.g-1 and in treated livers ranged from 1 to 21 nmol.min-1.g-1. For each of the various interventions, an increase or decrease in glutathione excretion was always accompanied by a change in bile flow in the same direction; however, these changes were not always directly proportional when comparisons were made between treatment groups. Nevertheless, when bile flow (microliter.min-1.g-1; ordinate) was plotted against glutathione excretion into bile for the pooled data, a significant correlation was observed that was adequately described by a straight line: y = 0.071 chi + 0.72 (r2 = 0.62, P less than 0.001). A similar function described the relation between bile flow and the sum of bile acids and glutathione in bile: y = 0.077 chi + 0.55 (r2 = 0.62, P less than 0.001). In contrast, the taurocholate- or glycocholate-induced choleresis had only minimal effects on glutathione efflux. These findings support the hypothesis that glutathione is one of the osmotic driving forces in bile acid-independent bile formation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2912150 TI - Cholecystokinin in pig plasma: release of components devoid of a bioactive COOH terminus. AB - Using radioimmunoassays specific for different sequences of cholecystokinin (CCK), we studied the intestinal release of CCK in pigs. After stimulation by intraduodenal infusion of HCl, plasma CCK concentrations, measured with an antiserum specific for the sulfated, bioactive sequence of CCK, increased from 1.4 +/- 0.7 to 42.7 +/- 11.7 pM in portal plasma and from 0.5 +/- 0.3 to 12.3 +/- 1.5 pM in peripheral plasma. The concentrations measured with an antiserum specific for the NH2-terminal sequence 5-10 of CCK-33 were considerably higher, increasing from 64 +/- 17 to 139 +/- 14 pM in portal plasma and from 69 +/- 7 to 102 +/- 9 pM in peripheral plasma. Chromatography suggested that the NH2-terminal immunoreactivity consisted of large CCK fragments devoid of the bioactive COOH terminal octapeptide, i.e., desocta and/or desnona CCK-58, CCK-39, and CCK-33. The bioactive forms in both portal and peripheral plasma comprised CCK-58-, CCK 33-, CCK-22-, CCK-12-, and CCK-8-like forms. Generally, the CCK-22-like component predominanated, but although CCK-8 was more abundant than CCK-33 in portal plasma, these forms occurred in equal amounts in peripheral plasma. Large amounts of NH2-terminal immunoreactivity were also found in the venous effluent of the isolated perfused duodenum after stimulation with gastrin-releasing peptide; the venous perfusate contained mainly CCK-22- and CCK-8-like material, which together constituted greater than 80% of the bioactive CCK components. Both duodenal and jejunal mucosa contained components resembling NH2-terminal fragments as well as large amounts of intact CCK-58 and CCK-33.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2912151 TI - Effect of coinfusion of cholic acid and sulfated cholic acid on bile formation in rats. AB - The effect of combined infusion of sulfated cholic acid and nonsulfated cholic acid on bile formation was investigated. The data show that the secretion of sulfated cholic acid is slower and does not share the same transport mechanism(s) as nonsulfated cholic acid. Sulfated cholic acid significantly increased bile flow and reduced the secretion of biliary phospholipids, cholesterol, and protein associated with the secretion of exogenous nonsulfated cholic acid, only when they were infused in a ratio higher than 2:1 (sulfated:nonsulfated). Thus it is concluded that sulfated bile acids may protect the liver against the toxic effect of high concentration of bile acids. The relevance of these findings to human cholestasis remains to be determined because sulfated bile acids do not predominate in serum during cholestasis. PMID- 2912152 TI - Reduction of 7-ketolithocholic acid by human liver enzyme preparations in vitro. AB - The formation of chenodeoxycholic and ursodeoxycholic acids from 7 ketolithocholic acid by human liver preparations was examined in vitro. Liver preparations were incubated with 7-ketolithocholic acid at pH 5.5 in a sodium potassium-phosphate buffer containing NADPH or NADH. The products formed were analyzed by gas chromatography and gas chromatography-mass spectrometry. Results showed that chenodeoxycholic and ursodeoxycholic acids could be formed from 7 ketolithocholic acid by human liver enzyme(s). The enzyme(s) required NADPH but not NADH as coenzyme and was localized largely in the microsomes. The conjugated 7-ketolithocholic acid, especially the taurine conjugated, was predominantly reduced to chenodeoxycholic acid, whereas the unconjugated 7-ketolithocholic acid was not reduced well to either chenodeoxycholic acid or ursodeoxycholic acid. Thus the reduction of 7-ketolithocholic acid by human liver enzyme(s) was found to be dependent on whether the substrate was conjugated or not. PMID- 2912153 TI - Uptake of bumetanide into isolated rat hepatocytes and primary liver cell cultures. AB - Uptake of bumetanide into rat liver cells was investigated using isolated hepatocytes and primary cell cultures. The kinetics of [3H]-bumetanide uptake revealed two saturable components in addition to an unsaturable component. Saturable bumetanide uptake consists of a high-affinity, sodium-dependent uptake and a low-affinity transport system. Bumetanide uptake into isolated rat hepatocytes is energy dependent and temperature sensitive. At low temperatures, bumetanide uptake is due to diffusion with a permeability coefficient of 1.16 x 10(-6) cm/s. In primary liver cell cultures, uptake of bumetanide decreases rapidly over 3 days. AS-30D ascites hepatoma cells do not take up bumetanide but bind small amounts of the loop diuretic. Hepatocytes metabolized bumetanide extensively. The metabolites were secreted into the surrounding incubation buffer. Two hydroxylated and at least one conjugated biotransformation product could be separated by thin-layer chromatography. Isolated rat hepatocytes possess carrier proteins for uptake of bumetanide and very likely also for uptake of other loop diuretics like furosemide, piretanide, and torasemide. Several inhibitors of multispecific transport systems in the kidney and liver were tested as potential inhibitors of hepatocellular bumetanide or furosemide uptake. Probenecid, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, iodipamide, digitoxin, bile acids, and bromosulfophthalein inhibited uptake of loop diuretics. Inhibition by taurocholic acid was competitive with a Ki of 24 microM. Taurocholic acid inhibited [3H]bumetanide uptake in the presence but not in the absence of Na+. Deoxycholic acid and bromosulfophthalein were noncompetitive inhibitors of hepatocellular bumetanide uptake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2912154 TI - Zinc absorption in human small intestine. AB - We determined the intestinal site of zinc absorption in humans and investigated the interaction between intestinal absorption of zinc and other solutes using the triple-lumen steady-state perfusion technique. Twenty-one healthy subjects participated in the study. During intestinal perfusion of a balanced electrolyte solution containing 0.1 mM zinc acetate, zinc absorption occurred throughout the entire small intestine. However, the jejunum had the highest rate of absorption (357 +/- 14 nM.min-1.40 cm-1) compared with the duodenum (230 +/- 33 nM.min-1.40 cm-1) and ileum (84 +/- 10 nM.min-1.40 cm-1). Over a range of zinc concentrations infused into the jejunum (0.1, 0.9, and 1.8 mM) there were linear increases in the rate of zinc absorption (P less than 0.05). Intestinal absorption of zinc was significantly stimulated by the addition of glucose (20 mM). Zinc absorption increased from 459 +/- 39 to 582 +/- 45 nM.min-1.40 cm-1 (P less than 0.05). Conversely, zinc (0.9 mM) also enhanced the absorption of glucose, which was increased from 293 +/- 43 to 447 +/- 27 microM.min-1.40 cm-1 (P less than 0.05). The enhanced absorption of zinc or glucose was not accompanied by any increase in absorption of water and sodium. In contrast, increasing the concentration of zinc in the perfusate resulted in decreased absorption of sodium and water in a dose related manner. In conclusion, our study demonstrated that zinc absorption is concentration dependent and occurs throughout the small intestine. The jejunum has the highest rate of absorption of zinc. The interactions between absorption of zinc and other solutes suggest that the transport process of zinc is carrier mediated. PMID- 2912155 TI - Tubular handling of neurotensin in the rat kidney as studied by micropuncture and HPLC. AB - Micropuncture studies were performed to assess the reabsorption and metabolism of the vasoactive peptide neurotensin (NT) in individual nephron segments and compare it to the handling of the closely related peptide bradykinin (BK). Rat proximal and distal convoluted tubules were microinfused with [3H]NT or [3H]BK. In a second set of experiments, [3H]NT and its metabolites in the ureteral urine were separated and characterized using high-performance liquid chromatography (HPLC) technique. The urinary recovery of 3H-labeled material was 31% when proximal tubules were microinfused with [3H]NT and 94% when distal tubules were infused. For proximal tubules the label recovered in the ureteral urine consisted exclusively of metabolites of NT and appeared as tyrosine, NT1-11, probably NT9 13, and two uncharacterized products. For distal tubules, 9% chromatographed as intact NT in the urine and except for the proportion the metabolites were almost identical to those found when proximal tubules were microinfused. Following microinfusion of [3H]BK into proximal tubules, the urinary recovery of 3H-labeled material was 19%. There was no correlation between fractional reabsorption of 3H labeled material and proximal tubular length when [3H]NT or [3H]BK was microinfused. In vitro incubation studies with rat ureteral urine showed extensive degradation of NT yielding tyrosine, NT1-6, probably NT9-13, NT, and two uncharacterized products. In contrast, there was no detectable breakdown of BK over a 32-min period. Finally, [3H]NT was incubated in rat serum, and these experiments also showed degradation of the peptide but not to the extent as when incubated in ureteral urine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2912156 TI - Regulation of organic osmolyte concentrations in tubules from rat renal inner medulla. AB - Glycerophosphorylcholine, inositol, and sorbitol were measured in rat kidney homogenates and tubules from inner medulla and papilla by enzymatic spectrophotometric techniques. Organic osmolytes exhibited their highest concentrations in the papillary tip. In contrast to glycerophosphorylcholine and sorbitol, inositol was of similar high concentrations in inner and outer medulla. Freshly prepared inner medullary tubules maintained tissue osmolyte concentrations under control, antidiuretic, and furosemide diuretic conditions. When tubules were incubated in vitro over 90 min, tubular organic osmolyte concentrations decreased as a function of extracellular NaCl, but not urea concentrations. Organic osmolyte disappearance from cells was quantitatively recovered from the medium. In contrast, medium lactate dehydrogenase activity did not rise in parallel and tubular ATP remained constant. Glucose up to a concentration of 200 mM increased tubule and medium sorbitol. The results obtained indicate that glycerophosphorylcholine, sorbitol, and inositol rapidly adapt their intracellular concentrations to extracellular NaCl osmolality by a change in tubular plasma membrane permeability. In addition sorbitol levels are regulated by the extracellular glucose concentration. PMID- 2912157 TI - Correlation of structure and function in developing proximal tubule of guinea pig. AB - Unlike the case in rat, rabbit, and other species in which nephron formation continues into the newborn period, nephrogenesis in the guinea pig is completed well before the time of birth. Therefore, the marked increase in proximal tubule reabsorption that occurs during the postnatal period in that species can be attributed entirely to an increase in the absorptive capacity of existing nephron units. The purpose of the present morphometric studies was to correlate that change in proximal tubule function with changes in the apical and basolateral cell membrane surface areas. The apical and basolateral membrane surface densities were found to be approximately equal to each other and to remain constant throughout development. Because of increasing tubule volume, however, both membranes doubled in size between 1 and 3 wk of age and eventually increased by a factor of 3.5 in the adult. At the same time, there was little change in the length of tight function complexes measured in the plane of the luminal surface. Using previously published functional data and tubule length data, a good correlation was found between absolute absorption and total basolateral membrane surface area throughout the entire period of development in proximal tubules. Absorption per unit area of basolateral membrane was approximately 0.55, 0.41, 0.56, and 0.42 X 10(-6) nl.min-1.micron-2 in the 1st, 2nd, and 3rd wk, and in adult animals, respectively, and thus was similar to that reported for proximal tubule segments of adult rabbit and juvenile to adult rat. PMID- 2912158 TI - K activity of CCD principal cells from normal and DOCA-treated rabbits. AB - We used liquid ion exchanger and conventional microelectrodes to evaluate the effects of mineralocorticoids on the intracellular K activity (aiK) and K transport properties of principal cells (PC) of isolated cortical collecting ducts (CCDs). Hoffman modulation optics and electrophysiological methods were used to identify PC. K activity was measured with two single-barreled electrodes. We found that aiK of PC from deoxycorticosterone acetate (DOCA)-treated rabbits (97.6 mM) was not different from controls (94.8 mM). The driving forces for K transport across the basolateral membrane favored cell to bath (reabsorption) in PCs from controls and bath to cell (secretion) in PCs from DOCA-treated rabbits. However, the driving force for K secretion across the apical membrane was not significantly different between the two groups. We used the intracellular aiKs and bath ion substitutions (gluconate for Cl and K for Na) to evaluate the effects of DOCA on the ion-selective properties of the basolateral membrane of PC. DOCA increased PK/PCl from 0.33 to 0.89. Our conclusion was as follows: in PC of control rabbits K is above electrochemical equilibrium across the basolateral membrane. However, the basolateral K conductance is probably too small for significant K recycling. In PC of DOCA-treated rabbits the aiK is below electrochemical equilibrium across the basolateral membrane and the K conductance is increased. These effects enhance K secretion across this border while maintaining cell K constant. PMID- 2912159 TI - Low-conductance K channels in apical membrane of rat cortical collecting tubule. AB - Low-conductance, K-selective channels were identified in the apical membrane of the rat cortical collecting tubule (CCT) by use of the patch-clamp technique. Isolated, split tubules were bathed in K gluconate medium to depolarize the cell while keeping the intracellular K concentration high. With the patch-clamp pipette containing predominantly either Na+ or Li+ but no K, outward currents were observed through channels that had a single-channel conductance (g) of 9 pS and a probability of being open (Po) of greater than 0.9, independent of the voltage (+/- 40 mV) applied to the pipette (Vp). Similarly, only outward currents were observed when the patch was excised into high-K solution, implying a high selectivity of the channel for K+. When 1 mM BaCl2 was added to the pipette, Po decreased to 0.36 at Vp = 0; however, g was not changed but the channels flickered rapidly between open and blocked states; Po decreased as Vp was made positive, and increased as Vp was made negative. With the pipette filled with KCl + 1 mM Ba, the channels conducted K+ in both directions. The inward currents (at positive Vp were larger than the outward currents (at negative Vp) and g near Vp = 0 increased to 25 pS. When the pipette was filled with RbCl + 1 mM Ba the inward and outward currents were similar in magnitude, suggesting that the channels can conduct Rb, although not as well as K. With the tubules bathed in NaCl Ringer solution and the pipette containing KCl, inward currents were observed that could be attributed to the same pathway for K.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2912160 TI - Intrarenal vasoconstriction during hyperchloremia: role of thromboxane. AB - The role of thromboxane (Tx) in chloride-induced renal vasoconstriction was studied in Munich-Wistar rats. Hyperchloremia (induced by changing an intra aortic, super-renal infusion of 1.2 M Na acetate to 1.2 M NaCl) reduced the glomerular filtration rate (GFR) by 31 +/- 3% (P less than 0.001; n = 27), and the clearance of p-aminohippurate (CPAH) by 36 +/- 4% (P less than 0.01). The Tx synthetase antagonists (25 mg/kg) UK-38,485 or OKY-046 prevented these changes. Pretreatment with indomethacin (5 mg/kg) also prevented Cl-induced changes in GFR and CPAH and blunted (P less than 0.05) the Cl-induced increase in renal vascular resistance (RVR, vehicle +55 +/- 11%, n = 8, indomethacin +27 +/- 7%, n = 6). Hyperchloremia reduced the hydraulic pressures (mmHg) in the outer cortical efferent arteriolar star vessels (PEA, 23.9 +/- 1.6 vs. 17.9 +/- 0.9; P less than 0.01) and proximal tubules (PT, 21.1 +/- 1.5 vs. 15.8 +/- 1.4; P less than 0.01) but not in the glomerular capillaries (PGC, 47.0 +/- 2.5 vs. 49.5 +/- 2.2; NS). Therefore the hydraulic pressure drop across the glomerular capillaries (PGC - PT) increased (24.9 +/- 2.8 vs. 34.6 +/- 2.9; P less than 0.02). UK-38,485 prevented significant Cl-induced changes in these pressures. The calculated resistances of the afferent and efferent arterioles both increased during hyperchloremia (+56 +/- 19%; P less than 0.05 and +195 +/- 66%; P less than 0.01, respectively) but were blunted after UK-38,485 (+23 +/- 8 and +21 +/- 10%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2912161 TI - In vivo generation of hydrogen peroxide by rat kidney cortex and glomeruli. AB - The purpose of this study was to demonstrate in vivo generation of hydrogen peroxide by rat renal cortex and glomeruli. Aminotriazole irreversibly inactivates catalase only in the presence of hydrogen peroxide, and previous studies have shown that aminotriazole-mediated inhibition of catalase is a measure of in vivo changes in the hydrogen peroxide generation. Aminotriazole injected intraperitoneally caused a dose-dependent (0.1-1 g/kg) and a time dependent (15, 30, 60, 90, 120 min) inhibition of the catalase activity in renal cortex. We confirmed that catalase inactivation by aminotriazole was due to formation of a catalase-hydrogen peroxide intermediate (compound I) because catalase inactivation was prevented by ethanol (2 g/kg), a competitive substrate for compound I. The specific activity of catalase in the glomeruli [0.27 +/- 0.026 k/mg protein (where k is the first-order reaction rate constant), n = 5] was significantly lower than the specific activity in the tubules (1.04 +/- 0.15 k/mg protein, n = 5) obtained from the same rats. The residual catalase activity (RCA) in the glomeruli (0.05 +/- 0.01 k/mg protein) was 19% of control values at 90 min after aminotriazole injection (1 g/kg). Taken together these data provide evidence for in vivo generation of hydrogen peroxide by rat renal cortex and glomeruli under normal conditions. Aminotriazole-mediated inhibition of catalase has been used in previous studies as a measure of in vivo changes in the hydrogen peroxide generation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2912162 TI - Effect of renal perfusion pressure on renal interstitial hydrostatic pressure in rats. AB - The purpose of this study was to investigate the hypothesis that changes in renal perfusion pressure may be transmitted to the renal interstitium and cause alterations in renal interstitial hydrostatic pressure and sodium excretion. A method that utilizes a chronically implanted polyethylene matrix that allows for direct continuous measurement of renal interstitial hydrostatic pressure, and agrees well with subcapsular measurement in rats, was developed. Renal interstitial hydrostatic pressure, fractional excretion of sodium, and urine flow rate were 3.0 +/- 0.3 mmHg, 0.35 +/- 0.13%, and 19.44 +/- 3.00 microliter/min, respectively, when renal perfusion pressure was 101 +/- 0.8 mmHg. When renal perfusion pressure was increased to 123 +/- 0.9 mmHg renal interstitial hydrostatic pressure, fractional excretion of sodium, and urine flow rate increased significantly to 5.8 +/- 0.6 mmHg, 1.29 +/- 0.29%, and 50.76 +/- 8.83 microliter/min, respectively, in anesthetized male Sprague-Dawley rats. These changes occur despite a well-autoregulated glomerular filtration rate and renal blood flow. In conclusion, increasing renal perfusion pressure caused a significant increase in renal interstitial hydrostatic pressure as measured directly by the implanted polyethylene matrix method and was associated with a significant increase in sodium excretion. PMID- 2912163 TI - Differential permeabilities of rat renal brush-border and basolateral membrane vesicles. AB - Potassium chloride permeability and relative ionic conductances of rat renal cortical brush-border (BBMV) and basolateral (BLMV) membrane vesicles were examined using the fluorescent probe 3,3'-dipropylthiadicarbocyanine iodide [diS C3-(5)]. Vesicles were simultaneously isolated and separated by free-flow electrophoresis. These studies demonstrated that neither BBMV nor BLMV equilibrated in 100 mM KCl despite prolonged incubation. In both, an inwardly directed KCl gradient was sustained for 3 h. The low intravesicular KCl concentration of BLMV was confirmed utilizing the response of electrogenic Na+ dependent [3H]glutamine transport to variations in the membrane potential. Chloride conductance was significantly less than potassium conductance in BBMV and BLMV. Consequently, an inside-positive potential was maintained across both membranes. BLMV were significantly more fluid, less permeable, had a lower relative chloride conductance, and maintained a greater inside-positive potential than BBMV. The KCl permeabilities of BBMV and BLMV were inversely related to endogenous membrane copper content and were significantly reduced by exogenous copper. Permeability did not correlate with membrane magnesium content, nor was it affected by exogenous magnesium. These studies suggest that endogenous copper as well as intracellular factors may regulate the permeabilities of the brush border and basolateral membranes of proximal tubule cells in vivo. PMID- 2912164 TI - Bicarbonate reabsorption by the kidney of the newborn rabbit. AB - Bicarbonate reabsorption by the immature kidney in response to acute acid-base changes was assessed in 50 anesthetized newborn rabbits before the end of nephrogenesis. The normal newborn rabbit (age 5-12 days) is in a state of hypochloremic metabolic alkalosis (PHCO3-, 31.9 +/- 0.6 mmol/l; PCl-, 83.1 +/- 1.0) and excretes a hypertonic (Uosmol = 578 +/- 41 mosmol/kgH2O), alkaline (UpH = 7.40 +/- 0.15) urine containing 50 +/- 9 mmol/l Cl- and 13 +/- 4 mmol/l Na+. The alkalosis is probably generated by an alkaline load contained in the mother's milk and maintained by a state of chloride wasting and volume contraction. In this alkalotic model, bicarbonate reabsorption, expressed per milliliter glomerular filtration rate (GFR), correlates positively with arterial CO2 pressure (PaCO2). The ability of the immature kidney to reclaim filtered bicarbonate in response to an elevation of the plasma carbon dioxide tension remains unlimited up to PaCO2 of 110 mmHg (y = 20.7 + 0.15 x, r = 0.82, P less than 0.001). Hypercapnia is associated with a marked fall in GFR, so that the positive correlation between bicarbonate reabsorption and PaCO2 vanishes when the bicarbonate reabsorption rate is expressed in absolute terms. Bicarbonate reabsorption is strongly dependent on the filtered load during both acutely induced metabolic acidosis and alkalosis. The acid-base state of the newborn rabbit is in sharp contrast with that of most animal species, and the renal handling of bicarbonate as a function of GFR does not show signs of tubular immaturity. PMID- 2912165 TI - Glomerular responses to platelet-activating factor in the rat: role of thromboxane A2. AB - In view of its role as a pro-inflammatory mediator in glomerular injury, we investigated the renal cortical microcirculatory responses to the intrarenal arterial administration of platelet-activating factor (PAF) in the anesthetized euvolemic Munich-Wistar rat. Close arterial administration of PAF led to dose dependent reductions in renal plasma flow rate (RPF), glomerular filtration rate (GFR), and filtration fraction (FF), in the absence of hypotension or hemoconcentration. Single-nephron (SN) plasma flow rate (QA), SNGFR and SNFF also fell [126 +/- 7 to 101 +/- 6 nl/min (P less than 0.005), 40.6 +/- 2.1 to 21.5 +/- 2.5 nl/min (P less than 0.005), and 0.33 +/- 0.03 to 0.21 +/- 0.03 (P less than 0.025)]. PAF increased pre- and postglomerular arteriolar resistances [2.32 +/- 0.14 to 2.73 +/- 0.19 (P less than 0.005) and 1.32 +/- 0.13 to 1.45 +/- 0.10(10)dyn.s.cm-5 (P less than 0.05)]. PAF infusion also led to a dramatic reduction in the mean value for the glomerular capillary ultrafiltration coefficient, Kf [0.058 +/- 0.012 to 0.020 +/- 0.003 nl.s-1.mmHg (P less than 0.025)]. PAF-induced changes in renal hemodynamics were abolished in the presence of the cyclooxygenase inhibitors, indomethacin and ibuprofen. When administered concomitantly with a thromboxane A2 (TxA2) receptor antagonist, PAF led to significant increases in RPF and GFR. In isolated glomeruli, PAF stimulated the biosynthesis of TxB2 in a dose-dependent manner. Thus PAF depresses rat glomerular function by inducing contraction of arteriolar and mesangial smooth muscle. These effects are likely mediated via the secondary release of TxA2. PMID- 2912166 TI - Renal metabolism of the oxidized form of ascorbic acid (dehydro-L-ascorbic acid). AB - We evaluated whether specific transport and metabolic properties exist in rat and guinea pig kidney for handling the immediate oxidative product of ascorbic acid, dehydro-L-ascorbic acid. Isolated tubules were used to measure uptake of 10 microM [14C]-dehydro-L-ascorbic acid over an 8-min incubation period. Uptake did not show dependence on the bathing media electrolyte composition but was inhibited to some extent by glucose. In tubules of both animal species the majority of 14C label present in the tissue extract was in the reduced form. No degredative enzymatic effect on dehydro-L-ascorbic acid is evident. Thirty-six percent of the [14C]dehydro-L-ascorbic acid reduced by the tubules was released during an 8-min incubation. Recently formed ascorbic acid is not substantially bound to cellular components. A factor necessary for dehydro-L-ascorbic acid reduction in renal cortex was found primarily in the 55-70% ammonium sulfate fraction. It is retained by mol wt 12,000 dialysis tubing, is heat labile, pH sensitive, inhibited by thiol reagents, and is most active in the presence of NADPH and glutathione. It has a molecular weight between that of blue dextran and cytochrome c as indicated by gel chromatography. We suggest that a cytosolic enzyme functions in reduction of dehydro-L-ascorbic acid and thereby is important in maintaining the redox state of ascorbic acid derived from the glomerular filtrate or from peritubular fluid. PMID- 2912167 TI - Role of renal interstitial hydrostatic pressure in the pressure diuresis response. AB - The present study examines the role of renal interstitial hydrostatic pressure (RIHP) in the pressure-diuretic and -natriuretic response. The relationships between RIHP, sodium excretion, and renal perfusion pressure (RPP) were determined in antidiuretic and volume-expanded (VE) rats with an intact or decapsulated kidney. RIHP was measured by use of the implanted capsule technique. RIHP increased significantly from 7.5 +/- 0.8 to 12.0 +/- 1.4 mmHg in VE animals and from 3.3 +/- 0.4 to 5.2 +/- 0.7 mmHg in antidiuretic rats after RPP was varied from 100 to 150 mmHg. The pressure-natriuretic response of the antidiuretic rats was blunted compared with that observed in the VE rats. Decapsulation of the kidney in VE rats lowered RIHP and reduced, but did not eliminate, the pressure-natriuretic response. To determine whether this residual response was related to changes in interstitial pressure in the medulla, cortical (CIHP) and medullary interstitial hydrostatic pressures (MIHP) were simultaneously measured in VE rats with an intact or decapsulated kidney. In control rats CIHP and MIHP were similar at all levels of RPP studied. In rats with the renal capsule removed MIHP was higher than CIHP and rose significantly from 6.7 +/- 0.8 to 9.2 +/- 0.8 mmHg when RPP was varied from 100 to 150 mmHg. These results indicate that pressure diuresis and natriuresis is accompanied by changes in RIHP and the response is modulated by the basal level of RIHP. These findings suggest that changes in MIHP may serve as an intrarenal signal for this response. PMID- 2912168 TI - Cyclosporine nephrotoxicity: blood volume, sodium conservation, and renal hemodynamics. AB - Glomerular filtration rate (GFR) and renal blood flow (RBF) are depressed by chronic cyclosporine treatment. We examined the hypothesis that depletion of extracellular or intravascular fluid volume contributes to the renal vasoconstriction of early cyclosporine nephrotoxicity (CCN). Control and CCN rats were given 10 mg/kg cyclosporine A or vehicle intramuscularly daily for 7 days. The effects of extracellular volume expansion, both acute (AVE, 10% body wt saline) and chronic (CVE, 10% body wt/day saline ip, 10 days including cyclosporine A treatment period), on renal hemodynamics were measured. In CCN, AVE completely normalized GFR and RBF, whereas CVE partially prevented the development of CCN. Renal autoregulatory ability was depressed in CCN but was largely restored by AVE. Intravascular volumes were measured with Evans blue and 51Cr-labeled red cells. Plasma and red cell volumes were reduced by 24% in CCN, indicating circulatory hypovolemia. Acute repletion of the deficit in blood volume by acute administration of an isoncotic solution (1.8 ml/100 g body wt of 5% albumin in isotonic saline) restored GFR and RBF to levels similar to those in control rats. Extracellular fluid volume, estimated as inulin space, was similar in both CCN and control groups. A metabolic study (7 day) showed stool Na loss in CCN to be twice that in controls but both groups remained in sodium balance. We conclude that the renal vasoconstriction produced in the rat by short-term cyclosporine treatment is, at least in part, prerenal in origin and related to the development of circulatory hypovolemia. PMID- 2912169 TI - Electrophysiology of collecting duct H+ secretion: effect of inhibitors. AB - Segments of the outer medullary collecting duct were isolated from the inner stripe of the rabbit kidney (OMCDi), perfused in vitro, and impaled across their basolateral membranes with voltage-recording microelectrodes. The disulfonic stilbene 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS) (10(-4) M) and the carbonic anhydrase inhibitor acetazolamide (10(-4) M) depolarized the lumen-positive transepithelial voltage (VT) toward 0 mV when added to the bath solution. Concurrently, the basolateral membrane voltage (Vbl) hyperpolarized. The hyperpolarization of Vbl, which averaged 19.3 +/- 2.9 mV (n = 11) for SITS and 22.7 +/- 3.5 mV (n = 11) for acetazolamide, was not due to an alteration in the ionic selectivity of the basolateral membrane, which was highly Cl- selective. The hyperpolarization of Vbl could best be explained by a decrease in the intracellular [Cl-], and the associated shift in the emf for Cl- (ECl) across the basolateral membrane. The decrease in intracellular [Cl-] could be attributed to inhibition of a Cl-HCO3 antiporter in the basolateral membrane. SITS appeared to inhibit this antiporter directly, whereas the effect of acetazolamide was indirect, probably secondary to a decrease in the intracellular [HCO3-]. Finally, both SITS and acetazolamide induced or unmasked an electroneutral K+-coupled transport system in the basolateral membrane. PMID- 2912170 TI - Role of BBM lipid composition and fluidity in impaired renal Pi transport in aged rat. AB - Renal tubular phosphate (Pi) transport is impaired in the aged rat. The decrement in Pi transport is manifested as a decrease in the Vmax of the luminal brush border membrane (BBM) sodium-dependent Pi transport. In the present study we determined the potential role of alterations in cortical BBM lipid composition and fluidity in the age-related phosphaturia observed in rats. In the aged rat there are significant increases in the BBM cholesterol (Chol, 504 vs. 422 nmol/mg protein in adult, P less than 0.01) and sphingomyelin (Sph, 41.8 vs. 37.5 mol% in adult, P less than 0.01) and a decrease in the BBM fluidity [increase in fluorescence anisotropy of diphenylhexatriene (DPH), rDPH, 0.221 vs. 0.215 in adult, P less than 0.01]. The BBM lipid compositional and fluidity alterations may also play an important role in the impaired renal adaptation to a low-Pi diet in the aged rat. In the adult rat the renal adaptation to a low-Pi diet is associated with a decrease in BBM Chol (370 to 307 nmol/mg protein, P less than 0.01) and an increase in fluidity (decrease in rDPH 0.207 to 0.201, P less than 0.05). In the aged rat the renal adaptation to a low-Pi diet is incomplete and is associated with impaired ability to lower BBM Chol (441 to 429 nmol/mg protein, P = NS) and to increase fluidity (rDPH 0.211 to 0.211, P = NS). The results of this study therefore suggest that in the aged rat the increase in BBM Chol and Sph content, and the decrease in BBM fluidity play an important role in the impaired renal tubular Pi transport and adaptation to a low-Pi diet. PMID- 2912171 TI - Pressor responses to vasopressin in pigs and sheep with DOCA hypertension. AB - Pressor responses to vasopressin were determined in pigs and sheep during three experimental periods: 1) before deoxycorticosterone acetate (DOCA) treatment, 2) 21 days after DOCA implantation (100 mg/kg) when a stable hypertension had developed, and 3) after reversal of the hypertension by removing the implant in the sheep or by decreasing the dietary sodium intake in the pigs. The infusion of lysine (LVP) or arginine (AVP) vasopressin into pigs and sheep, respectively, resulted in dose-dependent increases in plasma vasopressin concentration. The levels of plasma LVP or AVP achieved by these infusions were not altered in any of the experimental periods. The administration of vasopressin resulted in dose dependent increases in mean arterial blood pressure. However, pigs required five times more LVP than sheep required AVP to achieve similar pressor responses. The pressor responsiveness to vasopressin was attenuated when either species was made hypertensive. This effect was reversed when normal blood pressure was restored by reducing sodium intake in the pigs or by removing the DOCA implant from the sheep. These data establish that an increased pressor response to vasopressin does not contribute to DOCA hypertension in pigs or sheep. PMID- 2912172 TI - Sympathetic outflow to resting muscles during static handgrip and postcontraction muscle ischemia. AB - Simultaneous microneurographic recordings were made of muscle sympathetic activity (MSA) in the radial and the peroneal nerves of seven healthy subjects during 2-min static handgrip (30% of maximal voluntary contraction) followed by 2 min of forearm ischemia induced by arterial occlusion. At rest sympathetic burst frequency was similar in both nerves, but relative burst strengths differed between the two neurograms, suggesting that sympathetic outflows to arm and leg were not identical. Both radial and peroneal MSA were unchanged during the first minute of handgrip and increased to a similar degree during the second minute. Thus previously reported differences in vascular resistance between forearm and calf during static handgrip cannot be explained by differences in MSA to arm and leg muscles. During forearm ischemia after handgrip, peroneal MSA remained at the same level as during the second minute of handgrip but there was a further increase of radial MSA. This shows that stimulation of chemosensitive endings in forearm muscles induces differentiation of sympathetic neural outflow to muscles in the leg and the contralateral arm. PMID- 2912173 TI - Heart rate and blood pressure changes during sleep-waking cycles and cataplexy in narcoleptic dogs. AB - Cataplexy is the abrupt loss of muscle tone experienced by narcoleptics. It is usually precipitated by strong emotions or athletic activity. It has been hypothesized that cardiovascular variables have a role in the triggering of cataplexy. In the present study, we have utilized the narcoleptic canine model to directly investigate changes in heart rate and blood pressure in relation to cataplectic episodes. We found that heart rate increased 18% on average in the 20 s preceding cataplexy onset and then fell during cataplexy. Thus, from a cardiovascular standpoint, cataplexy can be subdivided into two very different periods, the cataplexy onset period with very high and declining heart rate, and the period greater than or equal to 10 s after onset, with greatly reduced heart rate. Heart rate at cataplexy onset was significantly higher than heart rate in rapid-eye-movement (REM) sleep, non-REM sleep, and quiet waking. Blood pressure did not markedly change before the onset of spontaneous cataplexies but decreased significantly during cataplexy. Although blood pressure increases did not precede spontaneous cataplexies, sudden increases in blood pressure, induced pharmacologically or by obstruction of the descending aorta, triggered cataplexy in the most severely affected subjects. A hypothesized role for cataplexy as a homeostatic reflex, triggered by interactions between blood flow, central chemoreceptors, and atonia control mechanisms in the medial medulla, is discussed. PMID- 2912174 TI - Role of prostanoids in cerebrovascular responses during seizures in piglets. AB - We examined the role of prostanoids to bicuculline-induced seizures in newborn pigs. Using the closed cranial window method and radioimmunoassay for prostanoids, we found that pial arterioles dilated during seizures; this dilation was associated with increased cortical periarachnoid cerebrospinal fluid (CSF) levels of prostaglandin E2, 6-ketoprostaglandin F1 alpha, prostaglandin F2 alpha, and thromboxane B2. Using radioactive microspheres, we found cerebral blood flow (CBF) increased dramatically during seizures in piglets. To examine the effects of pharmacological blockade of cyclooxygenase, we determined CBF in piglets pretreated with indomethacin (5 mg/kg) and in a corresponding group of piglets made hypothermic to be sure preseizure CBF values were similar. In the hypothermic group, CBF increased during seizure, but the increase in CBF during seizure in the indomethacin group was reduced dramatically in all brain areas. We conclude that 1) bicuculline-induced seizures result in pial arteriolar dilation and increased CBF; 2) CSF levels of prostanoids increase during seizures; and 3) pretreatment with indomethacin severely blunts increases in CBF during seizures. PMID- 2912175 TI - Microvascular rarefaction and tissue vascular resistance in hypertension. AB - The purpose of this study was to quantitatively estimate the relative contribution of arteriolar rarefaction (disappearance of microvessels) and arteriolar constriction to the increases in total peripheral resistance and changes in the patterns of flow distribution observed in hypertension. A mathematical model of the hamster cheek pouch intraluminal microcirculation was constructed based on data from the literature and observations from our own laboratory. Separate rarefaction and constriction of third-order (3A) and fourth order (4A) arterioles were performed on the model, and the results were quantified based on the changes of the computed vascular resistance. The degree of increase in resistance depended both on the number and the order of vessels rarefied or constricted and also on the position of those vessels in the network. The maximum increases in resistance obtained in the model runs were 21% for rarefaction and 75% for constriction. Rarefaction, but not constriction, produced large increases in the degree of heterogeneity of blood flow in the various vessel orders. These results demonstrate that vessel rarefaction significantly influences tissue blood flow resistance to a degree comparable with vessel constriction; however, unlike constriction, microvascular rarefaction markedly altered blood flow distribution in our model of the hamster cheek pouch vascular bed. These findings conform with the hypothesis that a significant component of the increase in total peripheral resistance in hypertension may be due to vessel rarefaction. PMID- 2912176 TI - Transfer function analysis of autonomic regulation. I. Canine atrial rate response. AB - We present a useful technique for analyzing the various functional components that comprise the cardiovascular control network. Our approach entails the imposition of a signal with broad frequency content as an input excitation and the computation of a system transfer function using spectral estimation techniques. In this paper, we outline the analytical methods involved and demonstrate the utility of our approach in studying the dynamic behavior of the canine cardiac pacemaker. In particular, we applied frequency-modulated pulse trains to either the right vagus or the cardiac sympathetic nerve and computed transfer functions between nerve stimulation rate and the resulting atrial rate. We found that the sinoatrial node (and associated automatic tissue) responds as a low-pass filter to fluctuations in either sympathetic or parasympathetic tone. For sympathetic fluctuations, however, the filter has a much lower corner frequency than for vagal fluctuations and is coupled with a roughly 1.7-s pure delay. We further found that the filter characteristics, including the location of the corner frequency and rate of roll-off, depend significantly on the mean level of sympathetic or vagal tone imposed. PMID- 2912177 TI - Transfer function analysis of autonomic regulation. II. Respiratory sinus arrhythmia. AB - An efficient new technique was developed to investigate heart rate control at all physiologically relevant frequencies by using respiratory activity as a frequency probe of the autonomic nervous response. The transfer function from respiratory activity to heart rate was determined during 6-min periods in which the respiratory rate was voluntarily controlled in a predetermined but erratic fashion. Changes in posture were used to manipulate autonomic balance. Respiratory sinus arrhythmia was determined to be a frequency-dependent phenomenon with the magnitude and phase characteristics of a low-pass filter. In agreement with previous work, at typical respiratory frequencies (greater than 0.15 Hz) increases in heart rate occurred simultaneously with the onset of inspiratory activity; however, at frequencies less than 0.15 Hz the phase relationship was quite different, such that increases in heart rate preceded inspiration. Between 0.15 and 0.45 Hz, the transfer magnitude was consistently lower while the subjects were in the upright posture than when in the supine posture, but below 0.15 Hz, it was equal in both postures. A model for respiratory modulation of heart rate, based on the atrial rate response characteristics determined in the companion paper [Am. J. Physiol. 256 (Heart Circ. Physiol. 25): H142-H152, 1989], suggests that the magnitude and phase characteristics of the subjects in the supine and upright postures differ because of relatively increased sympathetic outflow in the upright posture. A precise and efficient characterization of respiratory sinus arrhythmia can yield considerable insight into the autonomic regulation of the heart. PMID- 2912178 TI - Thoracic duct lymph flow and its measurement in chronically catheterized sheep fetus. AB - A method was developed for chronic catheterization of the left thoracic lymph duct at the base of the neck in the sheep fetus, which did not disrupt the other major lymphatic vessels that join the venous circulation at the same location. The lymphatic catheter was connected to a catheter in a jugular vein when lymph flow was not being recorded, so that the lymph continuously returned to the fetal circulation. Special consideration of catheter size to minimize flow resistance and treatment to prevent clotting were required. Individual animals were maintained up to 17 days with lymph flow continuing. In 13 fetuses averaging 128 days gestation (term = 147 days) at the time of catheterization, lymph flow rate was measured for 1 h each day for the first 7 postsurgical days with an on-line computer technique that continuously calculated lymph flow rate. Lymph flow averaged 0.64 +/- 0.17 (SD) ml/min in fetuses weighing 2.3-4 kg and tended to undergo a nonsignificant increase with time. Lymph and plasma protein concentrations did not change with time. In individual fetuses, large spontaneous variations in lymph flow rate occurred over periods of several seconds to a few minutes. Analysis showed that these variations in flow rate were not associated with fetal breathing movements. Thus the present study describes a technique for studying the dynamics of lymph flow in the unanesthetized sheep fetus in utero over a time period limited primarily by the length of gestation. In addition, it appears that thoracic duct lymph flow rate in the fetus per unit body weight averages three to four times that in the adult. PMID- 2912179 TI - Regional venous outflow, blood volume, and sympathetic nerve activity during severe hypoxia. AB - We examined the dynamic changes in venous outflow from the splanchnic, coronary, and remaining other vascular beds and changes in systemic blood volume (SBV) in response to severe hypoxia (PO2 = 17 mmHg) in dogs using cardiopulmonary bypass and a reservoir. Splanchnic venous outflow, which also includes renal outflow in this study, decreased by 40%, and coronary venous outflow increased by 400% at 3.5 min after initiating severe hypoxia. Severe hypoxia caused a marked decrease in SBV of 23 +/- 1 and 9 +/- 2 ml/kg in spleen-intact and splenectomized dogs, respectively. The decrease in SBV was attenuated by 60 (P less than 0.01) and 83% (P less than 0.01) after the carotid and aortic chemoreceptor denervation (which was accompanied by baroreceptor denervation) and after hexamethonium infusion (10 mg/kg), respectively. Sympathetic efferent nerve activity revealed a tremendous augmentation, which began to rise at a PO2 of 40 mmHg before chemoreceptor denervation and at a PO2 of 22 mmHg after denervation. These results show that severe hypoxia causes a marked decrease in SBV, 60% of which is caused by active splenic contraction, and suggest that the sympathetic efferent nerve activity, which is augmented by the stimulation of chemoreceptors as well as the central nervous system, contributes greatly to those hypoxic changes. PMID- 2912180 TI - Effects of hemodilution on gastric and intestinal oxygenation. AB - To determine the effects of hemodilution on gastric and intestinal oxygenation, isolated segments of canine stomach and small bowel were perfused by a pressurized reservoir with blood at hematocrits of 40 and 20%. Arteriovenous O2 difference, blood flow, and arterial and venous pressures were monitored continuously as perfusion pressure was reduced in 30-mmHg steps from 180 to 30 mmHg. O2 consumption was calculated as the product of the steady-state arteriovenous O2 difference and blood flow at each perfusion pressure. Gastric and intestinal O2 uptake were relatively well maintained over most of the pressure range when the hematocrit was set at 40%. After hemodilution, gastric O2 uptake decreased significantly only at 90 and 60 mmHg, but intestinal O2 uptake was significantly reduced except at 30 mmHg. When gastric and intestinal O2 uptake were plotted as a function of blood flow, the O2 uptake vs. blood flow relationship were shifted down and to the right by hemodilution. Hemodilution also linearized the O2 uptake vs. blood flow relationship in the intestine. However, when O2 uptake was plotted as function of O2 delivery, the gastric O2 uptake vs. delivery curves at the two hematocrits were superimposed on each other, but the O2 uptake vs. delivery curves for the intestine diverged except at low rates of O2 delivery. We conclude that by reducing the O2-carrying capacity of the blood, hemodilution adversely affects gastric and intestinal oxygenation. Our results also indicate that hemodilution lowers gastric O2 uptake by reducing O2 delivery; however, hemodilution lowers intestinal O2 uptake not only by reducing O2 delivery but also by impairing O2 extraction. PMID- 2912181 TI - Filtration coefficient in cat hindlimb using protein concentration changes. AB - The maximum value of capillary filtration coefficient (CFC) in maximally vasodilated cat skeletal muscle is disputed. It was hypothesized that the wide range of reported values was caused by the inability of gravimetric and volumetric measurements of tissue volume to separate transcapillary filtration from vascular volume changes. Consequently, we developed a method of measuring filtration rates from changes in venous protein concentration using Evan's blue labeled albumin in the isolated hindlimb (pentobarbital sodium anesthesia). The filtration coefficient (PFFC) calculated from these filtration rates after a step in venous pressure should not be influenced by vascular volume changes. When the perfusate flow rate through the hindlimb was greater than 15 ml.min-1.100 g muscle-1, PFFC was 0.0085 +/- 0.0015 (SD, n = 8) ml.min-1.mmHg-1.100 g muscle-1. PFFC was observed to be unvarying from 1 to 12 min after the venous pressure elevation, in contrast to CFC values, which fall during the same period. It is argued that the difference between CFC and PFFC values is caused by vascular volume changes. PMID- 2912182 TI - Magnesium and reperfusion of ischemic rat heart as assessed by 31P-NMR. AB - Isolated rat heart perfusion and high-resolution phosphate-31 nuclear magnetic resonance (31P-NMR) spectroscopy were used to elucidate the effects of Mg during reperfusion of the ischemic myocardium. After an ischemic period of 9 min, the hearts were reperfused with 0, 0.6, or 2.4 mM Mg during the entire 24-min reperfusion period or with 15 mM Mg during the first 12 min before returning to the physiological concentration of 0.6 mM during the last 12 min. Free intracellular Mg calculated by 31P-NMR rose during ischemia and fell gradually during reperfusion. The two groups reperfused with 15 mM Mg exhibited a significantly enhanced rate of recovery of adenosine triphosphate, creatine phosphate, intracellular pH, and coronary flow rate than the three other groups. Myocardial potassium was significantly higher, and inorganic phosphate was significantly lower at the end of the reperfusion period in these groups. The hearts reperfused with 0 mM Mg presented a significantly higher frequency of ventricular fibrillation (VF) than the other groups. It is concluded that reperfusion with high Mg improves the postischemic recovery of metabolism and function in the rat heart, whereas a Mg-free reperfusion solution increases the frequency of VF. PMID- 2912183 TI - Circulatory effects of PAF-acether in newborn piglets. AB - Platelet-activating factor (PAF-acether) is a lipid mediator that can exhibit potent vasoconstrictor influence in the pulmonary vessels. Therefore, the release of PAF-acether during inflammatory conditions in newborns might cause deleterious increases in pulmonary vascular tone. Thirty-four anesthetized open-chest newborn piglets were given 0.01-1 nmol PAF-acether iv. In separate experiments, animals were untreated or treated with either indomethacin (a cyclooxygenase inhibitor), SQ 29548 (a thromboxane receptor blocker), or LY 171883 (a leukotriene receptor blocker). The primary hemodynamic change was a 67 to 1,537% increase in the pulmonary vascular resistance index (PVRI) (P less than 0.01): mean pulmonary artery pressure (PAP) rose significantly at all doses tested, whereas only the largest dose consistently decreased cardiac index. Treatment with indomethacin or SQ 29548 prevented the decrease in cardiac index and attenuated the PAF-acether induced rises in PAP and PVRI. Vehicle and LY 171883 had no effect. The inhibitory influence of indomethacin and SQ 29548 suggests that an important component of PAF-acether's pulmonary vasoconstrictor action is mediated (at least in the newborn piglet) by cyclooxygenase products, most likely thromboxane. PMID- 2912184 TI - Ischemia-induced and reperfusion-induced arrhythmias: importance of heart rate. AB - The relationship between heart rate and ischemia-induced and reperfusion-induced arrhythmias was studied using 573 isolated rat hearts. Hearts (12/group), subjected to 7 min of coronary occlusion and 10 min reperfusion, were paced at 300, 330, 360, 390, 420, 480, or 540 beats/min. Pacing either throughout the experiment or during ischemia alone led to a rate-dependent increase in the incidence of reperfusion-induced ventricular fibrillation (VF) from 25% in the unpaced hearts to greater than 90% when the rate was 420 beats/min or higher. However, pacing during reperfusion alone did not increase the incidence of reperfusion-induced VF. In separate hearts, the right atrium was removed to permit examination of both low and high rates (167 +/- 2, 240, 336 +/- 3, or 480 beats/min throughout the experiment) over a wide range of durations of occlusion (3, 5, 7, 10, 15, 20, or 40 min). Ischemia-induced VF incidence was critically dependent on heart rate, low rates being protective. During reperfusion, the incidence of VF was also highly rate dependent if reperfusion was initiated within 10 min of the onset of ischemia (ranging from 8% when rate was 167 +/- 2 beats/min to 100% when rate was 480 beats/min) but was unrelated to heart rate when reperfusion occurred at later times (ranging from 33 to 50% when ischemia duration was 40 min). Heart rate can therefore influence susceptibility to ischemia- and reperfusion-induced arrhythmias, probably as a result of an effect on the rate of development of ischemic injury. PMID- 2912185 TI - Attenuated microvascular alterations in coarctation hypertension. AB - Arteriolar vasoconstriction, structural reductions in dilated diameter, and rarefaction have been observed in vascular beds with chronic renal hypertension. To determine their pressure or flow dependence, these functional and structural parameters were studied in the developing and chronic stages of coarctation hypertension in the cremaster muscle, a normotensive skeletal muscle bed that is protected from the effects of elevated microvascular pressures. Hypertension was produced in rats by placing a silver clip around the abdominal aorta above the branches of the renal arteries. In hypertensive rats, resting diameters were reduced in second-order arterioles after 4 and 8 wk, in third-order arterioles after 2, 4, and 8 wk, and in fourth-order arterioles after 4 and 8 wk, vs. controls. Vascular tone was elevated in second-order arterioles after 2, 4, and 8 wk and in third- and fourth-order arterioles after 8 wk in hypertensive rats. No increases in medial-intimal area were found at any stage of hypertension in any arteriolar order. The density of small arterioles (3rd-5th orders) was reduced by 20% in hypertensive rats at 8 wk but was unchanged at the other time periods. These arteriolar alterations, especially the absence of structural reductions in diameter, are attenuated compared with those observed in one-kidney, one-clip hypertension and suggest that most of the arteriolar alterations that occur in renal hypertension are pressure or flow dependent. PMID- 2912186 TI - Influence of nonuniformity on rate of left ventricular pressure fall in the dog. AB - We examined the influence of nonuniformity in regional ventricular function on the rate of left ventricular pressure fall in 10 anesthetized dogs. Ultrasonic segment gauges were implanted in the midwall of the anterior, lateral, and posterior left ventricle. In seven dogs, nonuniformity was produced by infusing isoproterenol (0.4 microgram/ml) into the mid-left anterior descending coronary artery at low flow (0.5 +/- 0.7 ml/min) and high flow (1.5 +/- 1.2 ml/min) rates, for total doses of 0.1 +/- 0.1 and 0.3 +/- 0.2 micrograms, respectively. This produced a dose-dependent increase in anterior segment shortening so that shortening was completed earlier and marked segment lengthening occurred during isovolumic relaxation. Lateral and posterior segments were not directly stimulated. The heart rate, left ventricular end-diastolic pressure, and peak systolic pressure remained constant. However, tau, the time constant of left ventricular pressure fall, increased from 32 +/- 8 to 37 +/- 10 ms with the low dose, and from 35 +/- 6 to 49 +/- 12 ms with the high dose of isoproterenol. Similar results occurred in two dogs when isoproterenol was infused into the proximal, mid, or distal left anterior descending and in three dogs with infusions in the left circumflex coronary artery. We conclude that nonuniformity of regional left ventricular function is an important and independent factor regulating the rate of pressure fall in the intact ejecting left ventricle. PMID- 2912187 TI - Adrenergic receptors of adrenal medullary vasculature. AB - The present study evaluates possible effects of adrenal catecholamines, released by splanchnic nerve stimulation, on adrenal medullary blood flow (MQ) and adrenal catecholamine secretion (CS). Twelve pentobarbital-anesthetized mongrel dogs were subjected to three identical splanchnic nerve stimulations (5 V, 20 Hz, for 3 min) at 30-min intervals, and MQ (radiolabeled microsphere technique) and CS (high-performance liquid chromatography) were measured before and during each nerve stimulation. Animals were assigned to one of three groups and administered either saline, pindolol (1 and 4 mg/kg), or prazosin (1 and 4 mg/kg) before the second and third nerve stimulation, respectively. In the saline control group, each nerve stimulation resulted in similar increases in MQ and CS. Pindolol attenuated nerve stimulation-induced increases in MQ and CS by 50%, but had no effect on medullary catecholamine concentration. Prazosin augmented nerve stimulation-induced MQ, CS, and medullary catecholamine concentration by 35%. These data suggest that adrenal adrenergic receptors modulate elicited CS and mediate changes in adrenal medullary vascular tone. PMID- 2912188 TI - Oxygen exchange in the microcirculation of hamster retractor muscle. AB - We determined percent hemoglobin oxygen saturation (SO2) in arterioles and venules of the hamster retractor muscle at rest. We found that SO2 decreased from 69.9 +/- 1.4% (SE) in large input arterioles (first order, 1A, ID = 60 +/- 3 micron) to flow-weighted values of 56.7% in small arterioles (4A, ID = 20 +/- 1 micron), 51.3% in small venules (4V, ID = 28 +/- 1 micron), and to 50.6 +/- 1.0% in large venules (1V, ID = 147 +/- 13 micron). Thus approximately two-thirds of the net decline in SO2 for this tissue occurred by diffusion of oxygen from arterioles, whereas only about one-third occurred by diffusion from capillaries. Furthermore, no net shunting of oxygen from the arterioles to the venules was detected as evidenced by the absence of any significant change in venular SO2. By determining the SO2 at upstream and downstream ends of arterioles in four consecutive branching orders (1A-4A), we found that the decrease in SO2 per unit length (delta SO2/L) increased approximately 20-fold from 1A to 4A. This increase in delta SO2/L was directly proportional to estimated luminal minus tissue oxygen tension and inversely proportional to red blood cell flow. PMID- 2912189 TI - Relation between phosphate metabolites and oxygen consumption of heart in vivo. AB - The relation between induced increases in cardiac work and phosphate metabolites was investigated in the canine heart in vivo to evaluate the role of ATP hydrolysis products, ADP and inorganic phosphate (Pi), in the control of myocardial oxygen consumption (MVO2). In these studies, myocardial blood flow and oxygen consumption were simultaneously measured with the 31P-nuclear magnetic resonance (NMR)-detected phosphate metabolites. Three protocols were used to increase myocardial work: pacing, epinephrine, and phenylephrine infusions. When these protocols were used, no or only slight changes in myocardial ATP, Pi, and creatine phosphate were observed with a greater than threefold increase in MVO2. The calculated intracellular free Mg concentration, ADP, and pH were also only slightly affected by these increases in work. These data indicate that a simple model involving the feedback of cytosolic ADP and Pi to the mitochondria regulating respiration is inadequate to explain respiratory control in vivo. These data suggest that some other parameters or cooperativity effects involving the phosphate metabolites must play a role in the feedback between respiration and work in the heart in vivo. PMID- 2912190 TI - Measurement of osmotic reflection coefficient for small molecules in cat hindlimbs. AB - Capillary osmotic reflection coefficients (sigma) for NaCl, urea, sucrose, and raffinose were measured in the isolated, perfused cat hindlimb using the osmotic transient technique. sigma were determined from the ratio of the maximum rate of transcapillary absorption [delta Jv(max)] to the increase in the osmotic pressure (25-35 mosmol/kg H2O) in the arterial inflow (delta pi a) produced by adding one of the molecules to an albumin-electrolyte perfusate containing isoproterenol (greater than 10(-7) M). delta Jv (max) was determined from organ weight and delta pi a from perfusate osmolalities. For each molecule, the delta Jv(max)/delta pi a ratio increased monotonically with perfusate flow rates (Q) to Q greater than 100 ml.min-1.100 g-1. This ratio was independent of the size of the delta pi a. Apparent sigma values were calculated by dividing these ratios by the capillary hydraulic capacity determined in other studies. At low Q, apparent sigma was comparable to the approximately 0.1 values found by others in skeletal muscle. At the highest Q, apparent sigma for these molecules were at least 0.5. These data are consistent with at least 50% of transcapillary water flow moving through a water-exclusive pathway. PMID- 2912191 TI - Relative importance of four pressoregulatory mechanisms after 10% bleeding in rabbits. AB - Four physiological mechanisms are known to be important for recovery of arterial pressure (AP) after acute hemorrhage. These are the sino-aortic baroreflex (SA), the vagally mediated cardiopulmonary baroreflex (CP), the renin-angiotensin system (RA), and the vasopressin system (VP). We evaluated in anesthetized rabbits the relative importance of these mechanisms by repeating rapid, 10% arterial hemorrhage (6.5 ml/kg) once before and once after eliminating one of them and comparing the posthemorrhage hypotension. The study was conducted in two series. In the first series, we randomly grouped 24 rabbits into four groups, i.e., a sinoaortic baroreceptor-denervated group (SA) a vagotomized group (CP), a renin-angiotensin-blocked group (RA), and a vasopressin-blocked group (VP). In control conditions, AP fell to 88% at 2 min and 92% at 6 min after completing the hemorrhage. Significantly greater hypotension (e.g., 74% at 6 min) occurred only in the SA group. In the second series, we randomly classified 18 rabbits into three groups, i.e., an autonomic ganglion-blocked group (AB) plus a RA group and a VP group as before. Hypotension significantly greater than control (68% opposed to 91% at 6 min) occurred only in the AB group. We submit that as far as restoration of arterial pressure after rapid, mild hemorrhage in the rabbit is concerned, the arterial baroreceptor reflex system plays a far more important role than the vagally mediated cardiopulmonary baroreflex, the vasopressin system, or the renin-angiotensin system triggered directly by a fall in renal arterial pressure. PMID- 2912192 TI - Distribution of perfusate flow during vasodilation in isolated guinea pig heart. AB - The purpose of this study was to determine the effect of vasodilation on the distribution of perfusate flow in the isolated guinea pig heart. Hearts were perfused retrogradely through the aorta with oxygenated Krebs-Henseleit buffer solution at 37 degrees C. Regional myocardial flows were measured with 15-micron radioactive microspheres. Each heart was subdivided into 45 pieces (average size 44 mg), and heterogeneity of flow was quantified as the relative dispersion (standard deviation/mean). Under control conditions at a perfusion pressure of 46 mmHg (60 cm water), the relative dispersion of left ventricular (LV) flow was 30 +/- 2% (n = 8). Vasodilation was induced via infusion of dipyridamole (10(-5) M). When flow was held constant at the resting value, relative flow dispersion increased to 43 +/- 6% (n = 8). When perfusion pressure was held constant and flow allowed to increase, relative dispersion fell to 20 +/- 5% (n = 5). Heterogeneity for the heart as a whole was higher than for the left ventricle but followed the same pattern with vasodilation. In a separate series of hearts (n = 5) equipped with LV balloons but without microsphere flow measurements, vasodilation at constant flow decreased LV pressure development, dP/dt, and O2 consumption. Vasodilation at constant pressure increased O2 consumption, but did not increase LV pressure or dP/dt. We conclude that vasodilation in this preparation will increase flow heterogeneity during constant-flow perfusion but decrease heterogeneity during constant-pressure perfusion. Furthermore, increased flow heterogeneity can compromise ventricular function. PMID- 2912193 TI - Errors in microsphere determination of cardiac output: a computer simulation in fetal sheep. AB - Through use of a compartmental model, we simulated the measurement of cardiac output and distribution by means of radioactively labeled microspheres in fetal lambs with weights between 0.5 and 3 kg. A systematic error in measured cardiac output caused by artifactual changes in blood volume caused by the injection and withdrawal of fluids during the procedure was less than 5% for fetal weights greater than or equal to 1 kg but increased for fetal weights less than 1 kg and when hypovolemia was simulated at all fetal weights. Sensitivity analysis disclosed no significant effect of changes in vascular resistance. We examined the effects of recirculation of microspheres and found no significant increase in error in the measured value of cardiac output due to 20% recirculation of all spheres entering a single isolated organ system; however, errors between 7 and 14% were observed with simulations of 20% recirculation in more than one compartment simultaneously. Recirculation also introduced significant errors in the measured distribution of cardiac output in certain cases. The effect on the measured cardiac output of a temporary change in the true cardiac output was dampened by the artifactual blood volume changes mentioned above and the fact that the measurement is a time-weighted average. We also evaluated four different experimental designs. We conclude that the microsphere technique provides a remarkably reliable means of quantifying cardiac output and individual organ flow in the fetus. The nonrandom errors inherent in the procedure examined in this study are of the order of 10%, which is likely to be less than the moment-to moment variation in the true cardiac output. PMID- 2912194 TI - Hypoxic reperfusion attenuates postischemic microvascular injury. AB - The results of several recent studies have demonstrated that reactive oxygen metabolites are responsible for a major portion of ischemia/reperfusion (I/R) injury in skeletal muscle. Presumably, the cytotoxic oxidants are produced during reperfusion when molecular oxygen (the source of the reactive oxygen metabolites) is reintroduced to the tissues. The purpose of this study was to test the hypothesis that molecular oxygen must be provided at reperfusion to produce I/R injury in skeletal muscle. Isolated, maximally vasodilated (papaverine) canine gracilis muscles were reperfused, after 4 h of inflow occlusion, from reservoirs containing autologous blood equilibrated with either 95% O2-5% CO2 or 95% N2-5% CO2 gas mixtures. Arterial PO2 fell from approximately 120 mmHg to less than 3-5 mmHg, during the use of nitrogen. The solvent drag reflection coefficient for total plasma proteins (sigma f) and total vascular resistance was determined for the following conditions: control (no ischemia), reperfusion with oxygenated blood after 4 h ischemia; and reperfusion (after 4 h ischemia), first with anoxic blood and then oxygenated blood. Reperfusion with oxygenated blood, after 4 h of ischemia, significantly reduced solvent drag reflexion coefficient (sigma f) from 0.93 +/- 0.02 to 0.63 +/- 0.02, indicating a dramatic increase in vascular permeability. Total vascular resistance increased from 6.1 +/- 1.1 mmHg.ml 1.min.100 g during the preischemic period to 12.9 +/- 3.0 mmHg.ml-1.min.100 g during normoxic reperfusion. In muscles reperfused with anoxic blood, sigma f averaged 0.82 +/- 0.06, whereas vascular resistance increased by 56 +/- 13%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2912195 TI - A rate-sensitive component to the myogenic response is absent from bat wing arterioles. AB - The responses of three sequential branching orders of arterioles in the bat wing to rapid and slow changes in transmural pressure were studied. Arterial and venous pressures to the wing were elevated simultaneously by pressurizing a box containing the body of the animal, while the wing was exposed to atmospheric pressure. Box pressure was elevated from 0 to +48 mmHg at two rates: 24 and 0.6 mmHg/s. During this time, continuous recordings of hydrostatic pressure and diameter were made in single arterioles using intravital microscopic techniques. Second-order arterioles and arcuate arterioles from skin and skeletal muscle constricted in response to elevated transmural pressure but did not show an enhanced response to rapid pressure changes. There was a trend for terminal arterioles to show a transient peak constriction during rapid stretch, but this response was always associated with a biphasic change in arteriolar pressure. These results suggest that the transient arteriolar resistance changes associated with rapid transmural pressure increases in previous experiments may be primarily a result of transient pressure changes in small arterioles. We find no evidence that arterioles in this preparation exhibit a rate-sensitive component to their myogenic response. PMID- 2912196 TI - Characterization of adenosine receptors in human pulmonary arteries. AB - We have characterized the effects of adenosine, the A1-receptor agonist N6-(L-2 phenylisopropyl)-adenosine (PIA) and the A2-receptor agonist 5'-(N-ethyl) carboxamido-adenosine (NECA), in isolated human pulmonary vessels. Fresh human lung tissue was obtained from nine patients, and small pulmonary arteries (200 400 micron ID) were dissected and mounted in an organ bath. The effects of the adenosine antagonist 8-phenyltheophylline (8-PT) and endothelial denudation were also studied. Adenosine, NECA, and PIA (1-300 microM) all caused a dose-dependent vasodilation with log EC30 values of -4.31, -4.31, and -3.53, respectively. 8-PT (10 microM) caused a rightward shift of the adenosine dose-response curve, significantly decreasing the effect of adenosine (pKB = 6.3). Mechanical removal of endothelial cells had no significant effect on adenosine-mediated vasodilation. We also compared the effects of adenosine on eight large (7-10 mm ID) and eight small (200-400 micron ID) arteries and found no significant difference in the sensitivity to adenosine between these vessels. Our findings suggest that the pulmonary vasodilator effects of adenosine in humans are mediated through A2 receptors that are localized to vascular smooth muscle. Adenosine may function as a regulator of pulmonary vascular tone in humans and may have therapeutic potential. PMID- 2912197 TI - Electrical and mechanical responses of rat saphenous vein to short-term pressure load. AB - The magnitude and mechanism of myogenic response of vascular smooth muscle (SM) in rat distal saphenous vein was assessed from SM membrane potential (Em) measured in situ and in vitro with glass microelectrodes and from active and passive stress and strain calculated from changes in vessel diameter measured in vitro via videomicroscopy. Elevation of intraluminal pressure from 2.2 +/- 0.2 (SE) mmHg (control) to 15 +/- 0.8 mmHg for 1 h in a series of in vitro vessel segments perfused with physiological salt solution at 0.2 ml/min induced a maintained and reversible depolarization of 18 +/- 0.9 mV. A 7.6 +/- 0.4-mmHg pressure increase induced a 12.9 +/- 1.2-mV depolarization in a second series. In a third series, 5-mmHg pressure increments induced significant increments in active isometric stress and isobaric strain. Opening an acute, reversible in situ femoral artery to saphenous vein shunt caused a 4- to 5-mmHg venous pressure elevation, a 10-fold increase in venous blood flow, and a 12.1 +/- 0.9-mV venous SM depolarization. Thus a short-term pressure load causes sustained, reversible venous SM cell depolarization both in vitro and in situ, coupled with active strain and stress generation in the vein wall. These results support our hypothesis that SM of peripheral veins can contribute to an intrinsic capacity autoregulation. PMID- 2912198 TI - Single-beat evaluation of left ventricular inotropic state in conscious dogs. AB - Two competing left ventricular elastic-resistive (ER) models were used to predict parameter values from pressure, volume, and time data of a single ejective beat in conscious dogs during control, enhanced (dobutamine), and decreased (propranolol) inotropic states. The animals were instrumented with three pairs of microcrystals and a transducer to measure intraventricular volume and pressure. Results showed that with the ER nonlinear model (ERNL), parameter values in all animals lay within the physiological range. These were the slope (Emax) and the intercept (V0) of the isovolumic end-systolic pressure-volume relationship (ESPVR), the slope of the end-diastolic pressure-volume relationship (Ed), the time to Emax (Tmax), the normalized time to end of activation (A), and the resistive constant (K). In the two models, the normalized SE of the estimate of data fitting was below 0.2 Emax, as estimated from a single beat, responded to changes in contractility in a significantly more consistent fashion than the slope of ESPVRs (Ees) generated by preload maneuvers in conscious dogs. Single beat estimated Tmax and K with the ERNL model did also respond consistently to contractility changes, whereas with the elastic resistive linear (ERL) model, K did not reproduce the experimental findings with decreased inotropic state. We conclude that 1) the ERNL model can be employed to assess contractility changes in conscious dogs from data of a single ejective beat, and 2) these changes are better indicated by single-beat estimated Emax than by Ees calculated from conventional ESPVRs. PMID- 2912199 TI - Alterations of coronary blood flow and reserve with aging in Fischer 344 rats. AB - To determine whether aging affects the coronary circulation, left and right ventricular coronary blood flow and vascular resistance at rest and after maximal vasodilation were measured by left atrial injection of radioactive microspheres in conscious, unrestrained male Fischer 344 rats at 4, 12, and 20 mo of age. As a function of age, maximal coronary blood flow per 100 g of tissue decreased by 43% in the left ventricle at both 12 and 20 mo, whereas a 44 and a 47% reduction was found in the right side of the heart at the same time intervals. Minimal coronary vascular resistance per 100 g of myocardium increased by 56 and 36% in the left ventricle and by 48 and 44% in the right at 12 and 20 mo, respectively. No change was found in total minimal coronary resistance for either ventricle despite an increase in myocardial mass. Maximal coronary blood flow per 100 g to the endocardium was depressed more than epicardial flow, leading to a 24% reduction in the endocardial-to-epicardial flow ratio at 20 mo. Coronary vascular reserve per 100 g, expressed as the increase in coronary blood flow during maximal coronary vasodilation, was greater in the right than in the left ventricle at all ages. It is concluded that the changes in coronary hemodynamics associated with maturation and aging are comparable with those seen in pressure overload hypertrophy with an increased vulnerability potential of the myocardium to ischemic episodes, particularly of the subendocardial region of the left ventricle. PMID- 2912200 TI - Shunting of leukocytes in rabbit tenuissimus muscle. AB - Leukocyte distribution was studied in 58 arterioles and capillaries constituting eight networks in the fascia adjacent to the rabbit tenuissimus muscle. Fluorescence video microscopy (acridine red) and digital image processing were used to visualize the leukocytes. Leukocyte concentration in the transverse arterioles leaving the muscle proper to irrigate the fascia was significantly elevated to 143 +/- 13% (mean +/- SE) of the systemic count. Leukocytes were found to further accumulate along the arteriolar tree, reaching 244 +/- 16% of systemic in the most remote branches. Leukocyte accumulation in the connective tissue can be calculated to lead to a decrease of leukocyte concentration in muscle capillaries to 89% of the systemic value. This shunting effect may be important in preventing leukocyte-induced capillary obstruction. At individual arteriolar bifurcations, leukocytes were found to preferentially enter the downstream branch with higher flow rate (regression coefficient 1.11 +/- 0.04, n = 100). This preferential distribution is quantitatively sufficient to account for the observed leukocyte distribution in the network. PMID- 2912201 TI - Ventricular function and fatty acid metabolism in neonatal piglet heart. AB - Studies in which subcellular systems were used suggest that neonatal myocardium has a sharply limited capacity to metabolize fatty acids. The relationship of these findings to the intact heart was tested on piglets, 8 h to 12 days of age. Left ventricular (LV) performance, O2 consumption (MVO2), and fatty acid (FA) uptake and oxidation were measured. Hearts were perfused at 70 cmH2O pressure with buffer containing 2% bovine serum albumin, insulin (100 microU/ml), 5 mM glucose, and 1.5 mM lactate. 14C-labeled palmitate was added (net FA, 0.5 mM). Washed erythrocytes were used to assure adequate O2 delivery. LV end-diastolic pressure (EDP) was controlled with a fluid-filled balloon. FA oxidation was estimated by measuring 14CO2 production. Hearts less than 24 h (group I, n = 6), those approximately 3 days (group II, n = 5), and those 6-12 days of age (group III, n = 10) were compared. Measurements at a low EDP (2-4 cmH2O) and at a higher EDP (7-9 cmH2O) were compared. At the low EDP, rates of FA oxidation for groups I III averaged 30.0 +/- 3.0, 31.4 +/- 2.9, and 50.2 +/- 2.6 nmol.min-1.g-1, respectively. These values increased to 43.8 +/- 3.7, 42.6 +/- 2.5, and 63.8 +/- 4.0 nmol.min-1.g-1, respectively, at the higher EDP level (P less than 0.01 for each group). Thus within a few hours of birth, pig hearts are able to oxidize long-chain FA, and the rate of oxidation is linked to mechanical function. However, both the oxidation rate and the percentage of MVO2 accounted for by FA oxidation are greater in older hearts. PMID- 2912202 TI - Thermal acclimation induces adaptive changes in subcellular structure of fish skeletal muscle. AB - Stereological analyses of electron micrographs were used to quantify physiologically important ultrastructures of slow-twitch oxidative (red) and fast twitch glycolytic (white) muscle fibers from striped bass (Morone saxatilis) acclimated to 25 and 5 degrees C. The fraction of cell volume occupied by the mitochondria [volume density, Vv (mit,f)] of red fibers increases from 0.286 +/- 0.018 to 0.448 +/- 0.024 between 25 and 5 degrees C; Vv (mit,f) of white fibers increased from 0.027 +/- 0.003 and 0.040 +/- 0.004 at 25 and 5 degrees C, respectively. Because of a concomitant increase in the mass of oxidative muscle, acclimation from 25 to 5 degrees C results in an increase in total mitochondrial volume per 100 g body wt from 2.58 to 6.73 cm3 in oxidative muscle and from 2.46 to 3.40 cm3 in fast glycolytic muscle. Mitochondria of red fibers are in more clustered arrays after cold acclimation. Size and cristae surface densities of individual mitochondria are not affected markedly by acclimation, suggesting true cold-induced proliferation rather than enlargement of organelles. Harmonic means of intermitochondrial spacing in red fibers decreases from 2.64 to 1.43 micron between 25 and 5 degrees C. This reduces diffusion path lengths between sarcoplasmic and mitochondrial compartments proportionately, compensating for decreases in diffusivity of aqueous solutes. Intracellular lipid droplets of red fibers markedly increase in volume density from 0.006 +/- 0.003 at 25 degrees C to 0.079 +/- 0.014 at 5 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2912203 TI - Bright morning light advances the human circadian system without affecting NREM sleep homeostasis. AB - Eight male subjects were exposed to either bright light or dim light between 0600 and 0900 h for 3 consecutive days each. Relative to the dim light condition, the bright light treatment advanced the evening rise in plasma melatonin and the time of sleep termination (sleep onset was held constant) for an average approximately 1 h. The magnitude of the advance of the plasma melatonin rise was dependent on its phase in dim light. The reduction in sleep duration was at the expense of rapid-eye-movement (REM) sleep. Spectral analysis of the sleep electroencephalogram (EEG) revealed that the advance of the circadian pacemaker did not affect EEG power densities between 0.25 and 15.0 Hz during either non-REM or REM sleep. The data show that shifting the human circadian pacemaker by 1 h does not affect non-REM sleep homeostasis. These findings are in accordance with the predictions of the two-process model of sleep regulation. PMID- 2912204 TI - Two-phase change of sympathetic rhythms in brain ischemia, Cushing reaction, and asphyxia. AB - The present study was designed to determine the extent to which the brain stem neural networks, normally capable of synchronizing the sympathetic nerve discharge (SND) into 2- to 6- and 10-Hz rhythmic fluctuations, contribute to the control of autonomic reactions during brain hypoxia and/or hypercapnia. Vertebral, cardiac, and renal nerve discharges were recorded electrophysiologically in 34 anesthetized, curarized, and artificially ventilated cats. The sympathetic nerve responses to cerebral ischemia (elicited by reducing the blood supply to the brain), intracranial pressure elevation (Cushing reaction), and systemic asphyxia were tested with special focus on the rhythmic structure of the SND. It has been found that there are two phases of SND changes during cerebral ischemia differing mainly in the frequency content of the signals and less in the compound action potential amplitude. During the first phase the rhythmic generators controlling the tonic sympathetic outflow are more strongly activated, which is reflected in a stronger, more regular, and more widespread manifestation of these rhythms on the efferent neurograms. After some time the normal SND structure abruptly changes to a desynchronized activity with loss of the three main sympathetic rhythms and responsiveness to baroreceptor reflex activation. The same stereotyped changes can be observed regardless of the way in which the brain hypoxia and/or hypercapnia has been produced. Nor does the denervation of peripheral baro- and chemoreceptors substantially alter the general pattern of the responses. PMID- 2912205 TI - Intracranial ethanol and ambient anoxia elicit selection of cooler water by goldfish. AB - Goldfish were either subjected to anoxia for 5 h at 10 degrees C, normoxia for 5 h at 10 degrees C, or were implanted with an intracranial microinjection cannula. All groups were subsequently tested in a temperature gradient. The previously anoxic goldfish selected cooler temperatures (12.8 +/- 1.0 degrees C; mean +/- SE) than the corresponding normoxic control group (17.5 +/- 0.7 degrees C) for the first 20 min in the gradient. Intracranial microinjections of 0.0475 ng ethanol in 0.2 microliter 0.7% NaCl led to the immediate selection of water 8.7 +/- 1.5 degrees C below that of base-line levels, whereas control animals injected with 0.7% NaCl selected water 0.9 +/- 1.0 degree C cooler. Increased effects were obtained with higher concentrations of ethanol. The effective site was limited to the anterior aspect of the nucleus preopticus periventricularis; injections into 54 other loci were without effect. Goldfish tolerate anoxia by the conversion of lactate to ethanol, which diffuses across the gills. As the lost ethanol cannot be oxidatively metabolized, this process is energetically inefficient. Because the concentration of the ethanol injections was considerably lower than reported ethanol concentrations in the tissues of anoxic goldfish, endogenously produced ethanol may have induced the selection of cooler water by the anoxic goldfish. This alteration in thermoregulatory behavior would lead to a lower metabolic rate, significantly increasing survival time during anoxia. PMID- 2912206 TI - Antidiuretic and pressor actions of vasopressin in age-dependent DOCA-salt hypertension. AB - The role of antidiuretic and pressor effects of vasopressin (VP) in deoxycorticosterone acetate (DOCA)-salt hypertension was studied in young and adult Brattleboro rats. The antidiuretic VP action was a necessary prerequisite for the development of severe DOCA-salt hypertension. The insufficient expansion of extracellular fluid volume in DOCA-salt-treated VP-deficient (DI) rats was associated with the attenuation of their hypertensive response, although they had highly increased blood volume and extracellular sodium. Chronic [deamino]-D arginine vasopressin supplementation that restored volume and distribution of body fluids in DI rats permitted the full development of DOCA-salt hypertension. Blood pressure response to DOCA-salt treatment was always greater in young than in adult Brattleboro rats (even in animals lacking pressor or both VP effects). In animals in which antidiuretic VP effects were present, the pattern of body fluid response to DOCA-salt treatment was also age dependent. There was a tendency to intravascular expansion in young hypertensive rats, whereas an increase of interstitial fluid volume was found in adult animals. The elimination of VP pressor action lowered systemic resistance much more in adult than in young hypertensive rats. We conclude that 1) in adult but not in young rats antidiuretic VP effects are essential for the occurrence of blood pressure response to DOCA-salt treatment, 2) the restoration of body fluids due to antidiuretic VP action enables the development of hypertension in both age groups of DI rats, and 3) pressor VP effects contribute to the maintenance of hypertension, especially in adult animals. PMID- 2912207 TI - Rare fatty acids in brown fat are substrates for thermogenesis during arousal from hibernation. AB - Because brown adipose tissue lipids are the preferred substrate for thermogenesis during arousal from hibernation, the fatty acid composition of brown fat lipids was followed during cold acclimation and during a hibernation bout. In control golden hamsters (living at 22 degrees C), the fatty acid composition of the white adipose tissue closely resembled that of the food, but brown adipose tissue contained more animal-derived fatty acids. As an effect of acclimation to cold, the fatty acid composition of brown adipose tissue changed to resemble that of the food, and no marked differences between white and brown adipose tissue were then evident. During a hibernation bout, a major part of the fatty acids accumulated in brown fat during entry into hibernation consisted of "rare" acids, such as homo-gamma-linoleic acid. Homo-gamma-linoleic, together with eicosadienoic acid and lignoceric acid, was preferentially utilized during the early phase of arousal. During this phase, "bulk" fatty acids, such as linoleic acid, were spared, whereas in late arousal, linoleic acid was the preferred substrate. It was concluded that rare fatty acids are of quantitative significance in brown adipose tissue during hibernation and arousal. PMID- 2912208 TI - Adrenal and sympathetic catecholamines in exercising rats. AB - The effects of adrenodemedullation and/or adrenoceptor agonists and antagonists on plasma epinephrine (E) and norepinephrine (NE) concentrations during exercise were investigated in rats. Exercise consisted of strenuous swimming against a countercurrent for 15 min in a pool with water of 33 degrees C. Before, during, and after swimming, blood samples were taken through a permanent heart catheter. E was not detectable in plasma of adrenodemedullated (Adm) rats. A marked reduction in the normal exercise-induced increase in plasma NE concentrations occurred in both Adm rats as well as in intact rats injected with the beta 2 selective adrenoceptor antagonist ICI 118551. Intravenous infusion of either E or the beta 2-selective agonist fenoterol restored the increase in plasma NE in Adm rats. Injection of the alpha 2-selective antagonist yohimbine in combination with infusion of the beta 2-selective agonist fenoterol into Adm rats caused an enormous increase in plasma NE. It is concluded that all NE in plasma as released during exercise originates from the peripheral nerve endings of the sympathetic nervous system. Adrenal E influences the release of NE via activation of presynaptic beta 2-adrenoceptors. PMID- 2912209 TI - Hyperprolactinemia prevents short photoperiod-induced changes in brown fat. AB - Previous studies demonstrated that short photoperiod exposure significantly decreases circulating prolactin levels. The present study investigated the possibility that concomitant changes in brown fat tissue mass, protein content, thermogenic capacity, and carcass composition are dependent on this change in prolactin levels. Male golden (Syrian) hamsters were sham operated and exposed to a short (10L:14D) or long (14L:10D) photoperiod. A third group was implanted with exogenous pituitaries under the right kidney capsule and exposed to a short photoperiod. In experiment I, 4 wk of short- vs. long-photoperiod exposure did not result in significant changes in circulating prolactin levels, nor was there an increase in brown fat mass, protein content, or thermogenic capacity. Four weeks of short-photoperiod exposure did significantly increase carcass lipid content. However, this increase did not occur in hamsters exposed to 4 wk of short photoperiod but made hyperprolactinemic (implanted with two exogenous pituitaries). Ten weeks of short photoperiod significantly reduced circulating prolactin levels. Concomitantly, brown fat mass, protein content, and thermogenic capacity, as well as carcass fat, were increased. These short-photoperiod-induced changes were not observed in similarly exposed hamsters that were made hyperprolactinemic via two implanted pituitaries. In experiment II, similar changes in brown fat and body composition occurred in sham-operated hamsters exposed to 10 wk of short photoperiod. These changes were prevented in hamsters exposed to 10 wk of short photoperiod but made hyperprolactinemic via only one implanted pituitary. These results suggest that decreased prolactin is a necessary condition for the increased brown fat mass, protein content, and thermogenic capacity that occurs when golden hamsters are exposed to short photoperiod. PMID- 2912210 TI - Effects of bombesin on food intake and gastric acid secretion in cats. AB - The brain and gut peptide bombesin has been reported both to stimulate gastric secretion and to induce satiety. To understand how the peripheral administration of bombesin affects food intake and whether gastric mechanisms are involved, a comparative study of the doses of bombesin active on gastric secretion, gastric emptying, and food intake was undertaken in cats provided with a gastric fistula and a denervated Heidenhain pouch. The smallest dose of intravenous bombesin that stimulated significantly basal acid secretion (20 pmol.kg-1.h-1) by the gastric fistula also enhanced meal-stimulated acid secretion by the Heidenhain pouch (+138%, P less than 0.01), delayed gastric emptying of a liquid protein meal ( 30%, P less than 0.01), and suppressed food intake when the test meal was allowed to reach the stomach (-15%, P less than 0.01). Conversely, in sham-feeding experiments, the same dose of bombesin increased food intake (+35%, P less than 0.01). In full-day experiments conducted in nonfasted cats, bombesin decreased both the food intake in the 4-h period after the infusion and the daily food intake, whereas octapeptide cholecystokinin induced a transient satiety but did not decrease daily food intake. These results indicate that in cats the interaction of bombesin with "pregastric" mechanisms is not sufficient to induce satiety and that a relation could exist between the effects of bombesin on gastric secretion, emptying, and food intake. A single class of receptors might be involved in these peripheral effects of bombesin. PMID- 2912211 TI - Morphological dynamics of ureteral transport. I. Shape and volume of constituent urine fractions. AB - Ureteral transport was studied in 50 urinary systems by urography with video recording in the upright and recumbent positions using low-osmolality and high osmolality contrast media. Morphometry and volumetry were applied to right urinary systems in which the urine-filled segments had a circular cross section at maximum peristaltic distension. The filling of the lumbar segment was composed of four fractions, each entering that segment by a specific mechanism: 1) the residual urine left behind by the preceding contraction ring, 2) the postcontraction injection from the pyelocalyceal system, 3) the extraperistaltic flow, and 4) the peristaltic injection produced by the pyelocalyceal contraction rings. The variations in the precontraction filling by fractions 1-3 and in the volume of fraction 4 gave rise to four types of transport. The junction between the lumbar and pelvic segments constituted a constant point of resistance to flow that prevented fractions 1-3 from entering the pelvic segment, the peristaltic injection into that segment being determined solely by the resistance at the junction and the volume of the bolus in the lumbar segment. Extraperistaltic flow to the bladder constituted a separate type of transport. PMID- 2912212 TI - Cardiovascular responses to intrathecal vasopressin in conscious and anesthesized rats. AB - Increases in mean arterial pressure and heart rate have been documented after the intrathecal administration of [Arg8]vasopressin (AVP) in rats. Prior studies in our laboratories with conscious rats indicated that these cardiovascular changes were associated with a marked hindlimb sensorimotor dysfunction. In this study, which represents the first systematic comparison of the effects of intrathecal AVP in conscious and anesthesized rats, we demonstrate that in conscious male Sprague-Dawley rats 1) the motor dysfunction induced by intrathecal AVP is accompanied by a rise in mean arterial pressure that is significantly greater than that produced by an equal intravenous dose of AVP, and 2) both paralytic and pressor effects of intrathecal but not intravenous AVP are blocked by the intrathecal administration of the V1-receptor antagonist d(CH2)5[Tyr(Me)2]AVP (V1 ANT) but are not blocked by intravenous phenoxybenzamine, hexamethonium, or [Sar1, Thr8]angiotensin II, an angiotensin II antagonist. In contrast, in anesthesized rats the arterial pressor response to intrathecal AVP was blocked by intrathecal V1-ANT, intravenous hexamethonium, and intravenous phenoxybenzamine. Furthermore, conscious but not anesthesized rats exhibited a tachyphylaxis to intrathecal AVP. These results indicate that intrathecal AVP produces both the cardiovascular changes and the sensorimotor deficits through interactions with centrally located V1-receptors. In addition, sympathetic catecholaminergic mechanisms mediate the rise in mean arterial pressure produced by intrathecal AVP in anesthesized rats, but they do not in conscious rats. PMID- 2912213 TI - Skeletal muscle calcium uptake in bacteremic rats. AB - To determine whether cellular Ca2+ regulation is altered in bacteremic rat skeletal muscle, 45Ca2+ uptake was measured in soleus muscles 12 h after an intraperitoneal bacterial (Escherichia coli) injection. Some rats received diltiazem (2.4 mg/kg iv) 10 h after bacterial injection to determine whether calcium blockers could inhibit changes in Ca2+ regulation. Cellular exchangeable Ca2+ was measured in soleus muscles incubated for 5 min to 4 h in Krebs-Ringer bicarbonate (KRB) media (pH 7.4) containing 45Ca2+ (1.5 muCi/ml) and subsequently "washed" in La3+-containing, Ca2+-free KRB media. Bacteremia had no effect on steady-state exchangeable Ca2+, but it significantly reduced the time required to reach half-maximal uptake compared with controls. Diltiazem treatment returned the half-maximal Ca2+ uptake toward control values in bacteremic rat muscles. Depolarization of soleus muscles with high K+ (60 mM) transiently increased Ca2+ uptake in control and bacteremic rat muscles, although the increase was significantly greater (P less than 0.05) in bacteremic rat muscles. The altered skeletal muscle Ca2+ regulation may be due to excessive stimulation of Ca2+ messenger systems, sarcolemmal Ca2+ channels, and/or Ca2+ release from the sarcoplasmic reticulum in response to bacteremia. PMID- 2912214 TI - Central action of acidic fibroblast growth factor in feeding regulation. AB - A phasic increase in activity similar to that of acidic fibroblast growth factor (aFGF) was detected in the cerebrospinal fluid of rats after feeding or after an intraperitoneal injection of glucose. This FGF-like activity in the cerebrospinal fluid was bioassayed in two systems: depression of the feeding response of Hydra and DNA synthesis-stimulating activity in BALB/c 3T3 cells after fractionation on a heparin affinity column. Dynamic feeding-related changes in activity of aFGF, basic FGF, and other growth factors were detected by both bioassay systems. Intracerebroventricular microinfusion of aFGF suppressed food intake in rats. Central infusion of inactivated aFGF, or peripheral administration of aFGF, in doses equivalent to or higher than those administered centrally was without effect. Electrophoretically applied aFGF specifically suppressed the activity of glucose-sensitive neurons in the lateral hypothalamus. Glucose-insensitive neurons were only slightly affected. The results suggest that aFGF may participate in the regulation of feeding at the level of the central nervous system. PMID- 2912215 TI - Adrenergic receptors on cerebral microvessels: pericyte contribution. AB - R224-R230, 1989.--[125I]iodocyanopindolol ([125I]ICYP) and [3H]rauwolscine were used to quantitate, respectively, the beta- and alpha 2-adrenergic receptors in freshly isolated bovine cerebral microvessels and in pericyte cultures derived from these microvessels. Morphological and immunocytochemical criteria distinguished the pericytes from endothelial cells. Competitive binding studies established the specificity of the radioligand binding. The maximal number of binding sites (Bmax) for [125I]ICYP in the pericytes constituted only 8% of that in the microvessels (3.5 +/- 1.3 vs. 44.4 +/- 6.6 fmol/mg protein). In contrast, the Bmax for [3H]rauwolscine in the pericytes was 50% of that in the microvessels (55.4 +/- 11.8 vs. 111.1 +/- 9.5 fmol/mg protein). The dissociation constants for both [125I]ICYP and [3H]rauwolscine were similar in the two preparations. No alpha 1-adrenergic receptors, as defined by the specific binding of [3H]prazosin, were identified either in the pericytes or microvessels. Overall, our results suggest that pericytes contribute minimally to the total beta-adrenoceptor number of cerebral microvessels, and thus the beta-adrenoceptors must be located predominantly on endothelial cells. However, the contribution of pericytes to the total alpha 2-adrenoceptor number of the microvessels may be substantial. PMID- 2912216 TI - Contribution of neurogenic mechanisms to control of intrinsic heart rate. AB - Altered autonomic tone as well as humoral factors can change the intrinsic rate of the cardiac pacemaker. To study the relationships of neurogenic and humoral factors on intrinsic heart rate (IHR) we used sinoaortic deafferentation (SAD) to increase sympathetic activity, lesion of nucleus ambiguus to reduce central parasympathetic activity, and one-kidney, one-clip (1K1C) renal hypertension to transiently increase the activity of the renin-angiotensin system and the combination of 1K1C hypertension with SAD. In conscious rats, IHR was determined using combined blockade with atropine and propranolol. Rats with 1K1C hypertension (7th day) showed increased mean arterial pressure (MAP), heart rate (HR), and IHR. Rats with SAD (4th day) demonstrated increased MAP and HR, but in contrast, had decreased IHR. Lesion of nucleus ambiguus increased HR and decreased IHR. When 1K1C hypertension was combined with SAD an additional increase in MAP and HR occurred, whereas IHR was reduced compared with renal hypertension alone. These data suggest that IHR is influenced greatly by autonomic tone and that the tachycardia in renal hypertension is linked to increased IHR that is dependent on integrity of the baroreflex. PMID- 2912217 TI - Relationship between respiratory state and intracardiac shunts in turtles. AB - Injection of radioactively labeled microspheres and blood O2 analysis from central vascular sites was utilized to assess intracardiac shunts in the unanesthetized and unrestrained turtle, Pseudemys scripta, at 15 degrees C. Both methods indicated a simultaneously occurring right-to-left (R-L) and left-to right (L-R) shunt during ventilation and apnea. During ventilation, the O2 method estimated a R-L shunt of 24%. In contrast, injection of microspheres during ventilation estimated a R-L shunt of 65%, which was significantly greater than the value determined from the O2 method. During apnea, both methods indicated a significantly larger R-L shunt. Estimates of the R-L shunt from O2 analysis were between 60 and 90% of the venous return. The R-L shunt estimated from the O2 content of left aortic arch blood was significantly greater than the value determined from right aortic arch blood. During apnea, the microsphere method estimated a R-L shunt of 79%, which was in the intermediate range calculated by the O2 method using two aortic arches. Our results verify previous reports of significant differences in R-L shunt levels between ventilation and apnea during the normal ventilatory cycle of turtles. PMID- 2912218 TI - Release of hypothalamic cholecystokinin in cats: effects of nutrient and volume loading. AB - Systemic cholecystokinin (CCK) suppresses food intake in various species and has therefore been proposed to act as a satiety factor. Because CCK is also present in the hypothalamus and furthermore meets neurotransmitter criteria, the hypothesis was tested whether CCK participates in the transmission of satiety messages at the lateral hypothalamic (LH) level. The results of this study demonstrate that in halothane-anesthetized cats, neurons located in the LH will indeed release CCK-like material after a carbohydrate-protein meal in a time dependent fashion. This release, as water loads demonstrate, is most likely due to volumetric distension rather than to the nutrient content. The releasable CCK does not originate from peripheral sources, since intravenously infused CCK octapeptide (CCK-8) does not appear in the perfusate. The release occurs only in discrete neurons and is not universal to CCK-releasing systems within the LH, and also, CCK-releasing systems are not present at all locations. The molecular form of CCK in feline hypothalamus is the COOH-terminal octapeptide (CCK-8) as shown by high-performance liquid chromatography. No gastrin-17 is present. CCK-8 is also the predominant form found in meal-induced as well as in KCl-induced CCK released from hypothalamic neurons. These results suggest a correlated role for hypothalamic CCK in the termination of food intake. PMID- 2912219 TI - Biomechanical and biochemical changes in lumbar vertebrae of rapidly growing rats. AB - Although growth-related biochemical, morphological, and biomechanical properties of rat cortical bone have been investigated, similar properties of immature rat vertebral bone have not been well characterized. Information about these properties is necessary, however, for comparative analyses of rat vertebral bone adaptation. Thus a method was developed to characterize growth-related differences in immature rat vertebral bone. The centra of sixth lumbar vertebrae (L6) of 44-day-old and 54-day-old male Sprague-Dawley rats were compressed to 50% of their initial height at a 50%/s strain rate while immersed in a potassium phosphate buffer solution (pH 7.4, 37 degrees C). Structural and material properties for the 54-day-old group that were significantly greater than those for the 44-day-old group included load, stress, and energy at the proportional limit; initial maximum load and stress; and load and energy at 50% strain. The structural stiffness of L6, as well as its elastic modulus, was significantly greater in the older animals. The calcium concentrations and calcium-to-collagen ratios in 54-day-old vertebrae were significantly greater than in younger animals. These results indicated that the specimen preparation and testing protocol developed for rat vertebrae produced reliable biomechanical results, even with the relatively small size of rat vertebrae bodies, and that the quantity and quality of the matrix of immature rat vertebral bone changed significantly during this period of rapid growth. Our test protocol will be useful for investigating the responses of rat vertebral bone to exercise, disease, and spaceflight. PMID- 2912220 TI - Brain stem mechanisms and the inhibition of angiotensin-induced drinking. AB - The present studies examine the effect of lesions of the ventrolateral region of the lateral parabrachial nucleus (VLLPBN) and of the area postrema and medial region of the nucleus of the solitary tract (AP/mNTS) on water intake induced by intracerebroventricular administration of angiotensin II (ANG II) and of the cholinergic receptor agonist, carbachol. Water intake was measured in rats with bilateral electrolytic lesions of the VLLPBN or thermocautery ablation of the AP/mNTS after intracerebroventricular delivery of ANG II (50 and 100 ng/2 microliter), carbachol (100 and 250 ng/2 microliter), and isotonic saline (2 microliter). Rats with lesions of the VLLPBN drank significantly more water during a 30-min test period to both doses of ANG II, but not to carbachol, than did sham lesion rats. Similarly, AP/mNTS lesion rats drank significantly more than sham lesion animals in response to the high dose of ANG II but not to carbachol. These results suggest that the previously reported exaggerated drinking responses to systemically administered ANG II demonstrated by rats with either VLLPBN or AP/mNTS lesions is not the result of a direct peripheral action of the octapeptide. Furthermore, the similarity of the induced drinking responses produced by these two lesions suggests that the AP/mNTS and the VLLPBN may be linked in a common thirst-mediating pathway. PMID- 2912221 TI - Prolactin stimulates food intake in a dose-dependent manner. AB - Lactation in the rat is marked by pronounced hyperphagia and suppression of brown fat (BAT) thermogenic capacity. We previously examined the possibility that elevated prolactin levels mediate these changes. The present study evaluated the effect of varying prolactin levels on food intake, BAT mitochondrial GDP binding, and carcass adiposity. Female rats were injected daily for 10 days with ovine prolactin at one of three doses: high = 3.0, medium = 1.0, or low = 0.3 micrograms/g body wt. Controls were injected with 0.9% NaCl. A group of uninjected rats served as an additional control. Cumulative food intake was significantly elevated in a dose-dependent manner in the prolactin-treated animals relative to the saline-injected and uninjected controls. Compared with the saline controls, the mean cumulative food intake was greatest at the high dose (20% increase), intermediate at the medium dose (17%), and smallest at the low dose (12%). Prolactin-treated rats gained significantly more weight during the experiment than did controls. Despite the hyperphagia in the prolactin treated rats, no significant differences in BAT mitochondrial GDP binding were observed among the five groups. These data indicate that elevated prolactin levels stimulate food intake in a dose-dependent manner and that this hyperphagia is not accompanied by an increase in BAT mitochondrial GDP binding. PMID- 2912222 TI - Sleep patterns in the genetically obese Zucker rat: effect of acarbose treatment. AB - Sleep patterns were continuously recorded in the genetically obese Zucker rat. Under normal feeding conditions, Zucker rats showed large amounts of slow-wave sleep (SWS) and normal amounts of pardoxical sleep (PS). In addition, both SWS and PS were equally distributed throughout the nychthemeron. When acarbose (an alpha-glucosidase inhibitor that slows absorption of glucose, reduces plasma insulin, and increases plasma somatostatin) was added to food pellets, the daily duration of SWS was markedly decreased, whereas PS was significantly increased. These results clearly show that sleep in the Zucker rat differs substantially from that classically observed in normal lean rats. In addition, they suggest that anomalies of insulin and somatostatin production and/or levels may cause the sleep disturbances observed in Zucker rats. PMID- 2912223 TI - Morphological dynamics of ureteral transport. II. Peristaltic patterns in relation to flow rate. AB - To study in the human the conditions for the flow regimes inherent in urinary systems with a dependence of the contraction interval on urine flow rate (boluses in-contact, leaky-bolus, and open-tube flow regimes), 50 urinary systems were examined at low and high flow rates. Morphometry and volumetry were applied to eight urinary systems. The bolus frequently contacted the preceding contraction ring but the mechanisms differed categorically from that conventionally postulated. Thus the contraction interval proved independent of flow rate, leading to boluses in contact not only at high but also at low flow rates, which is impossible in flow-dependent urinary systems. Likewise, contact proved possible with small as well as large boluses. Furthermore, the contact was invariably interrupted at the points of resistance to flow, the total contact period being only 4% of the ureteral transit. Leaky-bolus flow and open-tube flow were absent. The flow regimes as conventionally defined thus proved to be absent from and inconsistent with normal human urinary transport. PMID- 2912224 TI - Brown fat thermogenesis during hibernation and arousal in Richardson's ground squirrel. AB - The thermogenic activity [mitochondrial guanosine 5'-diphosphate (GDP) binding] and capacity (uncoupling protein concentration, cytochrome oxidase activity) of brown adipose tissue have been investigated at different phases of the seasonally linked hibernation cycle in Richardson's ground squirrel. The amount of axillary brown adipose tissue and the total mitochondrial content of the tissue were substantially greater in hibernating squirrels than in squirrels caught posthibernation in April or May; cold acclimation induced qualitatively similar differences. The specific mitochondrial concentration of uncoupling protein was high under all conditions (compared with other species), differing little between hibernating, posthibernating, and cold-acclimated squirrels. The thermogenic capacity of brown adipose tissue in Richardson's ground squirrels is therefore modulated almost exclusively by changes in the mitochondrial content of the tissue. Mitochondrial GDP binding was increased on cold acclimation, but similar binding levels were observed in hibernating and posthibernation (May) animals. GDP binding and the GDP-sensitive component of acetate-induced mitochondrial swelling were increased during the early stages of arousal from hibernation. These changes, which indicate an activation of the thermogenic proton conductance pathway in arousal, occurred without an alteration in the specific mitochondrial concentration of uncoupling protein. Increased GDP binding during arousal is clearly due to the unmasking of binding sites, reflecting an acute activation of preexisting uncoupling protein. PMID- 2912225 TI - Differential effects of cooling in hibernator and nonhibernator cells: Na permeation. AB - Unidirectional Na influx is less inhibited by cooling in guinea pig red blood cells than in ground squirrel cells. To isolate the source of this difference, component pathways of 24Na entry were estimated by use of selective inhibitors (ouabain, bumetanide, amiloride). Amiloride slightly inhibited influx in ground squirrel cells at every temperature between 37 and 5 degrees C. Amiloride did not consistently inhibit Na influx at 37 degrees C in guinea pig cells but caused a 44% inhibition at 25 degrees C and a 35% inhibition at 5 degrees C. Cytoplasmic acidification caused an increase in amiloride-sensitive influx in guinea pig cells, which was greater at 20 degrees C than at 37 degrees C; cytoplasmic acidification decreased amiloride-sensitive Na influx in ground squirrel cells at 37 degrees C and had no effect at 20 degrees C. PMID- 2912226 TI - Gastric emptying changes are neither necessary nor sufficient for CCK-induced satiety. AB - If gastric emptying plays a significant role in the satiety produced by exogenous cholecystokinin octapeptide (CCK-8) then 1) the effects on emptying and feeding should share similar kinetics and 2) peptides that inhibit emptying should also inhibit feeding. In the first experiment, CCK-8 (5.6 micrograms/kg) injected immediately before the introduction of an intragastric load (10 ml saline) or presentation of a test meal (15% sucrose) produced a rapid inhibition of both emptying and feeding. In contrast, the same dose administered 15 min before testing caused no inhibition of emptying, even though it retained the ability to reduce meal size. In experiment 2, the abilities of the peptides pentagastrin (100 micrograms/kg), bombesin (8 and 16 micrograms/kg), and secretin (2.86, 14.3, and 28.6 micrograms/kg) to reduce food intake and inhibit emptying were tested. Pentagastrin influenced neither food intake nor gastric emptying. Bombesin caused a small transient delay in emptying but a large and sustained eating suppression. However, a high dose of secretin caused no significant reduction of food intake, in spite of the fact that it inhibited emptying to the same degree as 1.4 micrograms/kg CCK-8, which does reduce intake. These results suggest that the inhibition of emptying by CCK is not sufficient to explain the satiety effect of CCK-8. PMID- 2912227 TI - Differences in perinatal NaCl exposure alters blood pressure levels of adult rats. AB - To determine the effect of differences in NaCl intake early in development on adult blood pressure levels, adult Sprague-Dawley female rats were maintained on diets containing either 0.12, 1.0, or 3.0% dietary NaCl throughout pregnancy and lactation. The offspring were continued on these same diets to 30 days postpartum. Thereafter, all offspring were maintained on the same stock diet containing 1% NaCl. Beginning at 60 days, systolic blood pressure and heart rate were measured weekly for the next 6 wk by tail-cuff plethysmography in lightly etherized rats. Mean arterial pressure (MAP) and heart responses to the subcutaneous sequential administration of 100 micrograms/kg angiotensin II and 15 micrograms/kg isoproterenol were then obtained from the catheterized femoral or carotid artery in awake unrestrained rats. Rats raised on 3% NaCl diet had significantly higher base-line MAPS (127.1 mmHg) than rats raised on the 1% (117.4 mmHg) or 0.12% (115.8 mmHg) salt diets. The highest salt group was also significantly more responsive to the pressor effects of angiotensin II (+46.4 mmHg) and the depressor effects of isoproterenol (-41.4 mmHg) than the mid- (+35.6 and -32.2 mmHg) and low- (+26.9 and -32.5 mmHg) salt groups. Thus there is a sensitive period early in ontogenesis of the normotensive Sprague-Dawley rat during which blood pressure and blood pressure responsiveness to angiotensin II and isoproterenol may be influenced permanently by dietary NaCl. PMID- 2912228 TI - Systemic vascular autoregulation amplifies pressor responses to vasoconstrictor agents. AB - Experiments were performed in seven conscious dogs to evaluate the contribution of total systemic autoregulation to the increase in mean arterial pressure (MAP) produced by the intravenous administration of pressor agents. Each dog was instrumented for the measurement of aortic pressure, central venous pressure, and cardiac output, and all dogs received hexamethonium to block autonomic ganglionic transmission. Angiotensin II (ANG II), arginine vasopressin (AVP), or norepinephrine (NE) were titrated over a 15- to 20-min period until MAP was increased to a new steady-state value approximately 50-55% above the normotensive control. Then while a constant infusion of the pressor agents was maintained, MAP was controlled via a gravity reservoir for 15-min periods at either the hypertensive value or at the animal's normotensive value. With all three pressor agents, total peripheral resistance (TPR) was greater when MAP was controlled at the hypertensive value than when the vasculature was protected from the elevated pressure by controlling MAP at the normotensive value. Thus a portion of the increase in TPR during the infusion of ANG II, AVP, or NE was due to autoregulatory-mediated vasoconstriction elicited by the increase in MAP. The fractions of the increases in TPR and MAP contributed by primary vasoconstriction vs. autoregulation were determined from the pressure-flow relationships. The pressure-induced increases in TPR accounted for 74% of the total increase in MAP produced by AVP, 62% of the pressor response to NE, and 34% of the response to ANG II. These results demonstrate that the direct vasoconstrictor effects of pressor agents can be significantly amplified by secondary autoregulatory responses. PMID- 2912230 TI - Correction to a 1980 article on CSF lactate and age. PMID- 2912229 TI - Self-induced water intoxication and alcohol abuse. AB - According to Feighner criteria, alcohol abuse was significantly more common among 17 schizophrenic male inpatients with self-induced water intoxication than among 17 matched schizophrenic control inpatients. The alcohol abuse had begun 8-22 years before the diagnosis of water intoxication. PMID- 2912231 TI - Clomipramine for bowel obsessions. PMID- 2912232 TI - Mania associated with high percentage of inhibition of monoamine oxidase. PMID- 2912233 TI - Acute distress after switch from Norpramin to generic desipramine. PMID- 2912234 TI - Diet-induced panic symptoms. PMID- 2912235 TI - DST response and pre-DST sodium levels. PMID- 2912236 TI - Polydipsia, hyponatremia, and psychosis. PMID- 2912237 TI - More on idiosyncratic reaction to naltrexone. PMID- 2912238 TI - Alcoholism and responsibility. PMID- 2912239 TI - Lying and the paranoid personality. PMID- 2912240 TI - Training in empathy. PMID- 2912241 TI - Certainty in medicine. PMID- 2912242 TI - In reluctant defense of dualism in psychiatry. PMID- 2912243 TI - Induction of mania by antidepressants. PMID- 2912244 TI - Basal ganglia calcification and organic mood disorder. PMID- 2912245 TI - Confidentiality in consultation-liaison psychiatry. PMID- 2912246 TI - Misconceptions about mentally ill patients. PMID- 2912247 TI - Pitfalls of inductivism. PMID- 2912248 TI - The current status of psychiatric education in alcoholism and drug abuse. AB - The authors conducted a survey of psychiatric education in alcoholism and drug abuse in the United States. Ninety-seven percent of 106 undergraduate training programs and 91% of 169 residency programs offered curriculum units in this field. Most of these programs also provided supervised clinical care. Areas of reported faculty dissatisfaction included problems with attitude and interest of psychiatric faculty and with the amount of curriculum time allotted. The authors conclude that although the amount of curriculum time devoted to training in alcoholism and drug abuse is growing, further investment in developing faculty and fellowships is warranted to increase the quality of teaching commitment. PMID- 2912249 TI - Treatment of cocaine-induced panic disorder. AB - The authors describe 10 patients who developed panic attacks only after substantial cocaine use. The timing of the onset of symptoms, i.e., after 1-6 years of cocaine use, and the fact that only one patient had a first-degree relative with panic disorder were more suggestive of acquired than primary panic disorder. The patients' atypical symptoms and responses to medications may be explained in terms of limbic-neuronal hyperexcitability induced by cocaine through a kindling mechanism. PMID- 2912250 TI - Observations of interactions of depressed women with their children. AB - Dysfunctional interactions between mothers with major affective disorders and their children may contribute to the children's high risk of disorder. This study investigated the behavior of mothers with recurrent unipolar depression, bipolar disorder, or chronic medical illness and of normal subjects toward their children during a directly observed conflict discussion task. In addition, lifetime history of depression, current mood, and chronic stress were investigated as predictors of maternal interaction. Unipolar depressed women displayed relatively more negative, less positive, and less task-focused behaviour toward their children. Current mood and chronic stress, more than psychiatric history, contributed to the prediction of interaction style. PMID- 2912251 TI - Use of DSM-III axis IV in clinical practice: rating etiologically significant stressors. AB - This study compared the etiologically significant stressors listed on DSM-III axis IV (severity of psychosocial stressors) with life events elicited by the Psychiatric Epidemiology Research Interview (PERI). Multiaxial evaluations of a diagnostically heterogeneous group of 362 patients were made, and all patients were subsequently administered the PERI by interviewers blind to the clinical assessments. The results indicated that axis IV functions well as a shorthand method for identifying the more severe psychosocial stressors. However, the DSM III requirement that the stressor be important in the development or exacerbation of the current disorder resulted in discrepancies between the axis IV and PERI assessments. PMID- 2912252 TI - Religious beliefs and practices among 52 psychiatric inpatients in Minnesota. AB - The authors studied the religious beliefs, practices, and experiences of 52 psychiatric inpatients. The rate of belief in the major tenets of faith (God, the Devil, and an afterlife) was uniformly high and in accord with national and local public poll results. Patients with depressive and anxiety disorders tended to score lower than those with other diagnoses on a wide variety of indexes of religion. The authors conclude that religion is an important factor in most patients' lives and that individual inquiry and systematic research into this neglected area are both feasible and important. PMID- 2912253 TI - Subspecialty training in alcoholism and drug abuse. PMID- 2912254 TI - Psychiatric resident dismissal: a national survey of training programs. AB - The authors report on a nationwide survey of psychiatric residency training directors who responded to a questionnaire designed to elicit information on the magnitude of the problem of unacceptable performance by residents. One hundred six program directors reported on 5,591 internship or residency positions from 1981 to 1985. A total of 184 residents (3.3%) were prematurely terminated or persuaded to resign; departmental deliberations were held on an additional 139 residents (2.5%). Reasons for dismissal and indications during the selection process that a trainee might prove problematic are discussed. A provocative finding was that 37% of terminated residents were accepted into other psychiatry training programs. PMID- 2912255 TI - Quantification of corpus callosum and ventricles in schizophrenia with nuclear magnetic resonance imaging: a pilot study. AB - Twelve chronic schizophrenic patients and 12 normal control subjects underwent magnetic resonance imaging of the brain. The schizophrenic patients had a significantly smaller corpus callosum area and higher ventricle-brain ratio than the control subjects. PMID- 2912256 TI - Salus populi. PMID- 2912257 TI - Four studies of mental health commitment. PMID- 2912258 TI - An empirical comparison of the stone and dangerousness criteria for civil commitment. AB - Massachusetts civil commitment criteria were compared in an emergency setting with a set of criteria developed by Dr. Alan Stone. Contrary to expectations, the Stone criteria proved to be more restrictive in a sample of 503 patients. Few patients would be newly committable under the Stone criteria; of the 35 patients committable under the Stone standard, 32 also met the current Massachusetts criteria for commitment. The clinical and policy implications of the adoption of the Stone criteria are discussed. PMID- 2912259 TI - Commitment: the consistency of clinicians and the use of legal standards. AB - The reliability and validity of the application of legal criteria for commitment were investigated as part of a larger study. Evaluations of 411 patients by 96 different clinicians showed good interrater reliability for assessment of dangerousness and committability. A strong relationship between ratings of committability and ratings of dangerousness suggests that clinicians were conforming to the logic of the commitment law. Discrepant cases involved patients who desired voluntary admission or whose commitment was completed elsewhere. Results suggest fair application of commitment standards but that two issues of statutory interpretation confused participating clinicians. PMID- 2912260 TI - An empirical study of emergency commitment. AB - The authors examine the emergency commitment process in one Oregon county and present data that document the impact of a local detention facility. The study reconfirms the dependence of commitment processes on the mental health system in which they occur, illustrates the relative inability of specific laws to determine the actual nature of commitment processes, provides support for the concept of community care for the people involved, and points to the need for additional research to clarify the effects of commitment procedures. PMID- 2912261 TI - Civil commitment standards and patient mix in England/Wales, Italy, and the United States. AB - Although England/Wales, Italy, and the United States share a common policy of deinstitutionalization, their mental health systems differ considerably. Each country's civil commitment standards define patient eligibility criteria along one of two primary dimensions--need for treatment or degree of dangerousness. These differential selection criteria result in mental health systems serving different subgroups of the total population. The criteria in England/Wales target older women; in the United States, younger men; and in Italy, a group balanced in age and sex. Implications for the current debate on civil commitment policies are considered. PMID- 2912262 TI - Premorbid sociosexual functioning and long-term outcome in schizophrenia. AB - Chronic schizophrenic patients with the most severe social deterioration have been shown to differ from other chronic schizophrenic patients with respect to measures of left-to-right ventricular asymmetry, negative symptoms, and response to haloperidol treatment. In the current study, the authors investigated the social antecedents of these characteristics of very poor outcome schizophrenia in 69 chronic schizophrenic patients. Poor premorbid sociosexual functioning was associated with more severe left-to-right ventricular asymmetry, greater severity of negative symptoms, fewer positive symptoms, and worse current social functioning. These data suggest that factors associated with severe social deterioration in the end stage of schizophrenia are also associated with premorbid sociosexual impairment. PMID- 2912263 TI - Hierarchy of characteristics associated with depressive symptoms in an urban elderly sample. AB - In contrast to the uncertainty about the prevalence and importance of late-life depressive disorders, a consistent pattern of risk factors for depressive symptoms has been shown by studies using the Center for Epidemiologic Studies Depression Scale (CES-D). The authors surveyed a representative sample of 2,137 elderly community residents with the CES-D and found a hierarchy of characteristics associated with substantial levels of depressive symptoms: illness, disability, isolation, bereavement, and poverty. If these findings are confirmed by prospective studies, addressing modifiable factors in the emergence, persistence, and remission of depressive symptoms might extend the independent survival of older adults. PMID- 2912264 TI - Parents' attitudes and patients' behavior: a prospective study. AB - The authors studied the behavior of 67 psychiatric inpatients and the attitudes of their parents toward their hospitalization. They found that certain parental concerns at admission correlated with particular aspects of patient behavior and ability to engage in treatment during the first 6 weeks of hospitalization. These findings have implications for the management of inpatient treatment. PMID- 2912265 TI - Social phobic symptoms in patients with panic disorder: practical and theoretical implications. AB - Of 35 patients with DSM-III-R diagnoses of panic disorder, 16 also received diagnoses of social phobia, and 15 of these 16 reported past episodes of major depression. Only nine of the 19 panic patients without social phobia had histories of depression. The panic patients with histories of depression had significantly higher self-ratings of social anxiety and avoidance, but not agoraphobic fear and avoidance, than those without histories of depression. Panic disorder and social phobia may coexist in many cases, and the presence of social phobia may be associated with a higher morbid risk for major depression in this population. PMID- 2912266 TI - Childhood sexual histories of women with somatization disorder. AB - The author interviewed 60 women with somatization disorder and 31 women with primary affective disorders who were matched for race, age at interview, and level of education to obtain their childhood sexual development histories. The two groups of women reported similar sexual experiences at similar ages, except that significantly more women with somatization disorder had been molested as children. PMID- 2912267 TI - High prevalence of obsessive-compulsive symptoms in patients with Sydenham's chorea. AB - The 20-item Leyton Obsessional Inventory--Child Version was completed by children and adolescents who had had Sydenham's chorea (N = 23) or rheumatic fever without chorea (N = 14). The Sydenham's chorea subjects had significantly more obsessive thoughts and compulsive behaviors and significantly greater interference from these behaviors. Three Sydenham's chorea patients but no rheumatic fever patients had substantial obsessional interference and met criteria for obsessive compulsive disorder when interviewed by telephone. This suggests that obsessive compulsive disorder, at least in some patients, may be due to basal ganglia dysfunction. PMID- 2912268 TI - Water excretion and plasma vasopressin in psychotic disorders. AB - To investigate the pathogenesis of water intoxication in psychotic disorders, a standard water load test was given to 23 unmedicated patients with schizophrenic or schizoaffective disorders. Levels of plasma arginine vasopressin were measured concurrently. Compared with 28 healthy volunteers, the psychotic patients had significantly smaller cumulative urine output and higher minimum urine osmolalities. Patients whose current illness had lasted less than 24 weeks exhibited the most severe antidiuretic state and also had the highest plasma arginine vasopressin levels. Water intoxication in acute exacerbations of psychosis may develop as a result of impaired excretory mechanisms. PMID- 2912269 TI - Continuing in treatment as a form of selection bias. AB - Panic patients who continued treatment (N = 12) did not have symptom scores significantly different from those of patients who declined or discontinued treatment (N = 12) but they did have lower pretreatment MHPG levels. Continuing in treatment may itself cause selection bias for biochemical variables under study. PMID- 2912270 TI - Ventricle-brain ratio and alogia in 19 young patients with chronic negative and positive schizophrenia. AB - In a group of 19 young patients with chronic mixed (both negative and positive) schizophrenia, the authors found that alogia was the only symptom to show a significant relationship to ventricle-brain ratio. PMID- 2912271 TI - Autoimmune thyroiditis and panic disorder. AB - Contrary to reports on depression, the prevalence of antithyroid antibodies was not significantly higher in 38 patients with panic disorder than in 38 matched control subjects. Autoimmune thyroiditis is not commonly associated with panic disorder but may play a role in some specific clinical circumstances. PMID- 2912272 TI - DSM-III subclassification of dissociative disorders applied to psychiatric outpatients in India. AB - In subclassifying 62 cases of DSM-III dissociative disorders in India, the authors found that 56 (90.3%) fell into the atypical subcategory. These cases could be easily separated into two additional subcategories, simple dissociative disorder and possession disorder, by using specified diagnostic criteria. PMID- 2912273 TI - Dangerously aggressive behavior as a side effect of alprazolam. PMID- 2912274 TI - Delirium in runners. PMID- 2912275 TI - Should dementia be recorded on axis II? PMID- 2912276 TI - Anticoagulant therapy for aggressive dementia patients. PMID- 2912277 TI - Patients' surreptitious taping of forensic psychiatric examinations. PMID- 2912278 TI - Psychoanalysis in the Soviet Union. PMID- 2912279 TI - Occult thyroid dysfunction in refractory depression. PMID- 2912280 TI - Deficit or negative syndrome? PMID- 2912281 TI - Imipramine and clonazepam for panic disorder. PMID- 2912282 TI - Unilateral ECT: medications and monitoring. PMID- 2912283 TI - Ethical concerns about new socioeconomic trends in mental health care. PMID- 2912284 TI - Videotape recording of assaultive inpatients. PMID- 2912285 TI - Need for geriatric psychiatrists. PMID- 2912286 TI - Effects of diagnosis and context on dangerousness. PMID- 2912287 TI - Countertransference and supervision. PMID- 2912288 TI - Decision making in the emergency room. PMID- 2912289 TI - Abstracts of papers and posters presented at the International Anesthesia Research Society, 63rd congress. Lake Buena Vista, Florida, March 4-8, 1989. PMID- 2912290 TI - A change in format for Anesthesiology. PMID- 2912291 TI - Effects of methemoglobinemia on pulse oximetry and mixed venous oximetry. AB - The performance of three commercially available pulse oximeters was assessed in five anesthetized dogs in which increasing levels of methemoglobin were induced. Hemoglobin oxygen saturation in each dog was monitored with three pulse oximeters (Nellcor N-100, Ohmeda 3700, and Novametrix 500) and a mixed venous saturation pulmonary artery catheter (Oximetrix Opticath). Arterial and mixed venous blood specimens were analyzed for PaO2, PaCO2, and pHa using standard electrodes. An IL 282 Co-oximeter was used on the same specimens to determine oxyhemoglobin and methemoglobin as percentages of total hemoglobin. Methemoglobin levels of up to 60% were induced by intratracheal benzocaine. As MetHb gradually increased while the dogs were breathing 100% inspired oxygen, the pulse oximeter saturation (SpO2) overestimated the fractional oxygen saturation (SaO2) by an amount proportional to the concentration of methemoglobin until the latter reached approximately 35%. At this level the SpO2 values reached a plateau of 84-86% and did not decrease further. When, at fixed methemoglobin levels, additional hemoglobin desaturation was induced by reducing inspired oxygen fraction, SpO2 changed by much less than did SaO2 (regression slopes from 0.16 to 0.32). Thus, at high methemoglobin levels SpO2 tends to overestimate SaO2 by larger amounts at low hemoglobin saturations. Plots of SpO2 versus functional saturation (oxyhemoglobin/reduced hemoglobin plus oxyhemoglobin) show an improved but still poor relationship (regression slopes from 0.32 to 0.46). The Oximetrix Opticath pulmonary artery catheter behaves similarly but provides somewhat better agreement with functional saturation than do the pulse oximeters in the presence of methemoglobinemia. Pulse oximetry data (SpO2) should be used with caution in patients with methemoglobinemia. PMID- 2912292 TI - Hyperbilirubinemia does not interfere with hemoglobin saturation measured by pulse oximetry. AB - This prospective clinical study evaluated the influence of high bilirubin plasma levels on the Nellcor pulse oximeter readings (SpO2). Twenty-nine icteric patients (mean total bilirubin 19.2 mg/dl, range 2.3-84.3 mg/dl) were compared with 46 controls. The difference between SpO2 and oxyhemoglobin percentage of hemoglobin (HbO2corr) or fractional saturation as measured by a seven wavelengths Corning Co 2500 Co-oximeter and corrected for the spectral error induced by hyperbilirubinemia in that co-oximeter was greater in icteric patients (bias and precision: 2.9% +/- 2.2% vs. 1.7% +/- 2.7%, P less than 0.03). However, icteric patients had also higher corrected carboxyhemoglobin levels (CoHbcorr) (1.8% +/- 0.7% vs. 1.3% +/- 0.8%, P less than 0.005) due to production of carbon monoxide during the catabolism of hemoglobin. Pulse oximeters read most of CoHb as oxyhemoglobin. After correcting SpO2 for carboxyhemoglobin in both groups of patients, the 99% confidence limits from the obtained regression line were the same in icteric patients (-0.81%, 1.03%) as in controls (-0.89%, 1.08%). There was thus no demonstrable direct influence of high bilirubin plasma levels on SpO2 as measured by a Nellcor pulse oximeter. PMID- 2912293 TI - Evaluation of a blood gas and chemistry monitor for use during surgery. AB - An observational study was performed to evaluate a new blood gas and chemistry monitor (GEM-6 Diamond Sensor Systems, Ann Arbor, Michigan) in nine patients during cardiac surgery. Paired blood samples were analyzed by the instrument under test and by standard clinical laboratory instruments. The differences between the measurements of the new and the standard instruments are summarized as follows (mean +/- standard deviation, units of measure, number of samples): pH (-0.039 +/- 0.02, 154); PCO2 (2.63 +/- 1.8 mmHg, 154); venous PO2 (-2.0 +/- 3.0 mmHg, 72), hematocrit (4.7 +/- 2.7%, 98), potassium (0.18 +/- 0.13 mmol, 100), and ionized calcium (0.195 +/- 0.11 mmol, 100). Because the differences in arterial PO2 measurements were markedly heteroscedastic, a logarithmic transformation was employed, which upon retransformation gave the test instrument's 95% confidence limits as within 5.1% below to 46% above the nominal value on 82 samples. However, on the 14 samples having nominal values below 165 mmHg (the upper limit of the calibrated range of the GEM-6) the 95% confidence limits were from 5.4% below to 23.6% above the nominal reading. No failures of the test instrument occurred during the evaluation, and quality control standards run before, midway through, and again after sampling from each patient all gave readings within the manufacturer's tolerance. For all variables except hematocrit and ionized calcium, this instrument matches the values from the laboratory well enough over the clinically important range to supplant it for intraoperative monitoring purposes. PMID- 2912294 TI - Effect of intercostal nerve blockade on respiratory mechanics and CO2 chemosensitivity at rest and exercise. AB - Lower intercostal and abdominal muscles interact with other respiratory muscles to produce inspiration as well as expiration. Intercostal nerve blockade from T6 T12 was produced in seven healthy males to study its effect on: 1) supine pulmonary function, 2) inspiratory effort, 3) hypercapnic ventilatory response, including mouth occlusion pressures with and without an expiratory load, and 4) ventilation during progressive exercise on a cycle ergometer. Studies during control and blocked states were performed on different days. Lower chest and abdominal wall paralysis was documented with electromyography. Findings include a minimal decrease in peak expiratory flows with intercostal blockade (P = 0.02), but no other changes in supine resting pulmonary function tests, inspiratory effort, or hypercapnic ventilatory response slopes. Minute ventilation, respiratory rate, and VT/TI during exercise were also minimally increased, indicating an increase in the drive to breathe, which was unrelated to a change in metabolic rate. During exercise, total time to exhaustion was decreased following intercostal nerve blockade. Bilateral intercostal nerve blockade produced minimal decreases in peak expiratory flow at rest in supine subjects. During seated exercise, there was a slight increase in respiratory drive, probably due to minor alterations in the mechanics of breathing induced by intercostal blockade. The authors conclude that, in healthy young subjects, intercostal nerve blockade does not exert a clinically significant adverse affect on pulmonary mechanics and that ventilatory function is well-maintained even at extremes of ventilatory demand. PMID- 2912295 TI - Treatment of isorhythmic A-V dissociation during general anesthesia with propranolol. PMID- 2912296 TI - Fiberoptic endobronchial intubation for resection of an anterior mediastinal mass. PMID- 2912297 TI - Postpartum seizure after epidural blood patch and intravenous caffeine sodium benzoate. PMID- 2912298 TI - Caudal epidural anesthesia in an infant with epidermolysis bullosa. PMID- 2912299 TI - Pain of delayed traumatic splenic rupture masked by intrapleural lidocaine. PMID- 2912300 TI - Dose-response relationship for succinylcholine in a patient with genetically determined low plasma cholinesterase activity. PMID- 2912301 TI - Determination of decay constants from time-varying pressure data. PMID- 2912302 TI - Succinylcholine and trismus. PMID- 2912303 TI - An infant model to facilitate endotracheal tube fixation in the pediatric ICU patient. PMID- 2912304 TI - An alternative method for management of accidental dural puncture for labor and delivery. PMID- 2912305 TI - High-pressure uterine displacement. PMID- 2912306 TI - Midazolam in a malignant hyperthermia-susceptible patient. PMID- 2912307 TI - Air entrainment through a multiport injection system. PMID- 2912308 TI - A tracheal tube extension for emergency tracheal reanastomosis. PMID- 2912310 TI - Appropriate facilitation of intravenous regional techniques in RSD. PMID- 2912309 TI - The relationship between malignant hyperthermia and neuroleptic malignant syndrome. PMID- 2912311 TI - Comparison of hemodynamic, electrocardiographic, mechanical, and metabolic indicators of intraoperative myocardial ischemia in vascular surgical patients with coronary artery disease. AB - To compare mechanical, electrocardiographic, and metabolic indices of myocardial ischemia, the cardiokymogram (CKG), the V5 ECG, left anterior descending coronary artery territory lactate extraction, and pulmonary capillary wedge pressure (PCWP) were measured in 53 vascular surgical patients with coronary artery disease. Measurements were performed preoperatively and at four specific intraanesthetic intervals: after tracheal intubation, before surgery, and 10 and 30 min after incision. Measurements and sampling sequence took 5-7 min, and therapy for the probable cause of ischemia was instituted following completion of this sequence. Myocardial ischemia was defined as type II or III CKG, 0.1 mV or greater horizontal or downsloping depression of V5 ECG ST segment, 0.2 mV or greater elevation of V5 ECG ST segment, or myocardial lactate production. Thirty nine patients (74%) had a total of 89 episodes of myocardial ischemia. Seventy four episodes (83%) were detected by the CKG, 31 (44%) were evident on the ECG, and 13 (15%) by evidence of lactate production. The concordance among the indices of myocardial ischemia was poor. Patients with an abnormal preoperative ECG experienced a greater number of ischemic episodes (P less than 0.001). Elevation of PCWP or the presence of A-C or V-waves greater than 5 mmHg above the mean did not individually reflect ischemia reliably. Intraoperative myocardial ischemia is common in vascular surgical patients and is most sensitively detected by ventricular wall motion abnormality. PMID- 2912312 TI - Changing perspectives in monitoring oxygenation. PMID- 2912313 TI - Transurethral resection of the prostate, serum glycine levels, and ocular evoked potentials. AB - Complications of transurethral resection of the prostate (TURP syndrome) when glycine is used as the irrigating fluid include cardiovascular and central nervous system abnormalities that occasionally include transient blindness. Serum sodium, glycine, potassium, chloride, ammonia, osmolality, carbonate, and blood urea nitrogen of 17 patients having TURP and 10 having cystoscopic examination were measured. Electroretinograms and visually evoked potentials (VEPs) were recorded in the preanesthetic preparatory area and in the recovery room immediately after surgery. Four patients reported visual aberrations coincident with increases in serum levels of glycine from a mean before surgery of 137.7 +/- 45.1 to 7,812.2 +/- 2,486.6 microM/l, mean +/- SD, after TURP. These patients also showed a reduction of serum sodium from 138 +/- 4.5 to 122 +/- 8.6 mEq/l that correlated significantly with serum levels of glycine (rho = -0.81). There were no statistically significant changes of serum ammonia and osmolality. Electroretinograms consistently demonstrated complete loss of oscillatory potentials. Thirty hertz flicker-following was also abolished. VEPs were more variably affected with prolongation of component "P100" latency found in both groups and probably resulting from sedative effects of diazepam. Patients experiencing the TURP syndrome showed abolishment of 30 Hz flicker-following in their VEPs. The elevated serum levels of glycine may contribute directly to visual aberrations resulting from glycine's role as an inhibitory transmitter in the retina. PMID- 2912314 TI - Studies in animals should precede human use of spinally administered drugs. PMID- 2912315 TI - Determination of intra-abdominal pressure using a transurethral bladder catheter: clinical validation of the technique. AB - The determination of intra-abdominal pressures (IAP) may be useful in many clinical situations. The authors recently demonstrated in the canine model a close correlation between actual IAP and the bladder pressure measurements obtained from a transurethral catheter. The purpose of this study was to clinically validate this technique. The authors studied 16 patients, and compared IAP in three positions (supine, with compressions, and semi-erect) utilizing both direct intraperitoneal pressure monitoring and the pressure obtained with a transurethral bladder catheter. Their results demonstrated a linear relationship between the two methods described, with a mean r value of 0.95 in the supine and semi-erect positions, and 0.99 with abdominal compressions (P less than 0.0001). The authors conclude that transurethral monitoring of bladder pressure offers a safe, simple, and highly accurate method for evaluating IAP at the bedside. Studies evaluating the indication for its use in the operating room and intensive care settings appear warranted. PMID- 2912317 TI - The influence of dextrose administration on neurologic outcome after temporary spinal cord ischemia in the rabbit. AB - The influence of dextrose administration on neurologic outcome after temporary spinal cord ischemia was examined in New Zealand white rabbits. Spinal cord ischemia was produced by infrarenal balloon occlusion of the aorta in unanesthetized animals. Animals were observed for 3 days for neurologic evaluation. Fasted animals received intravenous dextrose, 0.5 g.kg-1, or placebo before a period spinal cord ischemia. The dextrose was administered as either a bolus of a 50% solution (D50) 15 min before ischemia or as an infusion of a 5% solution (D5W) over 90 min before ischemia. With either mode of administration, preocclusion plasma glucose level was moderately increased as compared with that in animals that received lactated Ringer's solution in equivalent volume, i.e., for the D50 bolus: 291 +/- 82 (SD) versus 166 +/- 67 mg.dl-1 (P less than 0.005); and for D5W infusion: 177 +/- 38 versus 137 +/- 13 mg.dl-1 (P less than 0.01). With either mode of administration, neurologic outcome was poorer (P less than 0.025) at 72 h in the animals that had received dextrose. For example, of the 10 animals that received D5W by infusion, nine were paraplegic (unable to walk) 72 h after ischemia, whereas only three of 10 control animals were paraplegic. The adverse effect of an increased blood glucose level has been demonstrated previously for cerebral ischemia. The present results are the first demonstration that increased plasma glucose may result in a worsened neurologic outcome after spinal cord ischemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2912316 TI - Epidural clonidine analgesia in obstetrics: sheep studies. AB - Epidural clonidine administration produces analgesia by a nonopiate, spinal mechanism, and offers advantages over other epidural agents for labor analgesia. To examine clonidine's acute maternal and fetal effects, the authors injected clonidine, 300 micrograms, epidurally in seven chronically prepared, near term ewes. Unlike epidural saline injection, clonidine increased maternal and fetal serum glucose (by 178 +/- 30% and 190 +/- 30%, respectively; mean +/- SEM, P less than .01) 1 h following injection. Maternal and fetal serum cortisol and arterial blood gas tensions were unchanged following clonidine. Epidural clonidine injection produced minor decreases (10-15%) in heart rate in ewe and fetus, without altering maternal and fetal blood pressure, intra-uterine pressure, or uterine blood flow. Maternal and fetal serum clonidine concentrations peaked at 58 +/- 8 and 73 +/- 5 min following injection, respectively, and declined with similar half-lives. Heart rate correlated negatively with serum clonidine concentration in both ewe and fetus (P less than .05). Apart from hyperglycemia, which does not occur in humans, these results in sheep suggest that epidurally administered clonidine does not adversely affect the fetus and may be evaluated as an analgesic in obstetrics. PMID- 2912318 TI - Tachyphylaxis to local anesthetics does not result from reduced drug effectiveness at the nerve itself. AB - Possible development of tachyphylaxis to local anesthetics in the nerve itself (time-dependent change in axonal conduction properties) was studied in the aortic nerve of eight rabbits anesthetized with urethane. The nerve was immersed in Tyrode solution with or without bupivacaine at pH 7.4 and 38 degrees C in a trough molded from the surrounding tissues. After control measurements the nerve was exposed to increasing bupivacaine concentrations until complete nerve block at minimal blocking concentration. Subsequently, bupivacaine concentrations were reduced and kept constant for 4 h (partial block). Finally, intact nerve function was confirmed after bupivacaine washout with Tyrode solution. For quantification total nerve activity was recorded continuously and related to drug concentrations. Two findings argue against the occurrence of tachyphylaxis at the nerve itself: 1) nerve activity decreased rather than increased over time in the presence of constant bupivacaine concentrations during partial block; and 2) for the same bupivacaine concentration, nerve activity during partial block was always lower than during the initial blocking experiments. Thus, drug effectiveness increased rather than decreased over time, which cannot be reconciled with the theory that tachyphylaxis might be mediated by changes in axonal conduction properties. PMID- 2912319 TI - Comparison of the effects of halothane on skinned myocardial fibers from newborn and adult rabbit. I. Effects on contractile proteins. AB - The effect of halothane on maximal and submaximal Ca2+-activated tension development of the contractile proteins of newborn and adult cardiac muscle from rabbits was determined. Right ventricular muscle was removed from newborn and adult rabbits, and the sarcolemma was disrupted (skinned) by homogenization. Fiber bundles were dissected from the homogenate and mounted on tension transducers. Fiber bundles were alternately immersed in relaxing solution [( Ca2+] less than 10(-9) M) and contracting solutions (various [Ca2+] from 10(-5.6) to 10(-3.8) M), which were saturated with 100% N2 alone or with three concentrations of halothane-N2 mixture. In the absence of halothane, newborn skinned myocardial fibers were slightly more sensitive to submaximal Ca2+ concentrations than were adult myocardial fibers. [Ca2+] required for 50% maximum tension were 10(-5.43) M and 10(-5.31) M, respectively (P less than 0.05). Halothane (1-3%) decreased the maximal Ca2+-activated tension (at [Ca2+] = 10( 3.8) M) similarly in adult and newborn myocardial fibers in a dose-dependent fashion. Tension was reduced by 5.9% for each 1% increase in halothane concentration. Halothane also decreased the sensitivity of adult myocardial skinned fibers to submaximal Ca2+ concentrations (10(-5.6) M to 10(-5.0) M) by shifting the Ca2+-tension response curve to the right. Only 3% halothane decreased the sensitivity of newborn myocardial skinned fibers to Ca2+. The authors conclude that halothane causes less depression of Ca2+ activation of the contractile proteins in newborn than adult rabbit myocardium and that this effect of halothane cannot account for greater negative inotropy of halothane in the newborn. PMID- 2912320 TI - Regional differences in left ventricular wall motion in the anesthetized dog. AB - Data regarding left ventricular function suggest that the extent of shortening may differ between regions. This study was undertaken to determine the effects of negative inotropic drugs used during anesthesia on different areas of the left ventricle. Forty mongrel dogs were anesthetized and instrumented for measurement of global and regional function. Regional function in the short axis of the basal and apical territories of the left ventricle was assessed by subendocardial sonomicrometry. Three different interventions were performed: In the first group 67% N2O, replacing 67% N2, was added to opiate anesthesia; in the second group halothane was given by stepwise increases in inspired concentration to 2%; in the third group verapamil (60 micrograms.kg-1.h-1) was infused during isoflurane anesthesia. Apical and basal segmental shortening were compared. During baseline conditions and with agents in concentrations that caused minimal myocardial depression (67% N2O or 1.0% as opposed to 0.5% halothane) differences in systolic shortening between regions were statistically significant. Further myocardial depression affected the apex significantly more than the base: when substantial myocardial depression was induced by halothane (1.5 or 2%) or verapamil, differences in regional function were abolished. Thus, the apical region of the left ventricle is more dynamic and more sensitive to negative inotropic interventions than the basal region. This should be borne in mind when segmental myocardial function is evaluated. PMID- 2912321 TI - Additives contained in drug formulations most frequently prescribed in Switzerland. AB - The presence of substances known to induce pseudoallergic reactions was investigated by means of a questionnaire to the manufacturers of 1,467 frequently administered formulations. Benzoates were found in 15% of the formulations, sorbates in 5.5%, sulfites in 3.8%, and benzalkonium in 3.0%. The occurrence of the seven artificial colours studied was as follows: indigotin 7.8, erythrosine 7.4, sunset yellow 6.6, tartrazine 4.9, quinoline yellow 2.8%, ponceau (new coccine) 2.6, and amaranth 1.7%. A significant risk of exposure to preservatives and dyes likely to induce asthma, urticaria, or other pseudoallergic reactions exists for all individuals taking commercial drug products. PMID- 2912322 TI - Effect of an aerosol delivery system on bronchodilator activity. AB - Metered dose inhalers (MDIs) are often used incorrectly by patients who find difficulty using MDI for drug inhalation. The study was performed in 11 asthmatic patients in four days in order to evaluate the efficiency of a new Drug Delivery System (DDS-InspirEase) for metered dose inhalers. Clenbuterol was administered via DDS and via conventional MDI in a randomized manner. On the first two days, DDS and MDI were used by patients without any physician's help. On the subsequent days, clenbuterol was administered via DDS and via conventional MDI directly by the physician. FEV1 and MEF75 values were measured 15', 30', one hour, and two hours post-drug inhalation. Statistical analysis (ANOVA) showed that clenbuterol delivered by DDS, administered by patients or by physician, produced a greater increase in FEV1 values (P less than .05) and MEF75 values (P less than .01) in comparison to the conventional MDI on each test day. No significant differences existed between physician or patient administration of clenbuterol with DDS and MDI. The results showed a greater bronchodilator effect obtained by clenbuterol delivered by DDS. PMID- 2912323 TI - Analysis of indoor environment and atopic allergy in urban populations with bronchial asthma. PMID- 2912324 TI - Two rapid methods for determination of serum theophylline concentrations: a comparison. AB - Two methods for determining serum theophylline concentrations were compared against a standard laboratory assay. Each method was evaluated for ease of use, accuracy, and precision. Although both methods were found to be easy to use, there were major differences between the assays in both accuracy and precision. PMID- 2912325 TI - Inability to elicit vagal responses from the acid-infused esophagus of pigs. AB - Acid application in the esophagus and esophageal distension were undertaken in pigs. One group (n = 9) had operatively induced esophagitis. The other group (n = 7) was normal. We found no discrepancy between the groups neither in inspiratory pressure nor in expiratory PCO2 nor in plasma concentrations of pancreatic polypeptide. The results indicate inability to elicit vagal responses from the acid-infused esophagus of pigs. PMID- 2912326 TI - The superiority of combination beclomethasone and salbutamol over standard dosing of salbutamol in the treatment of chronic asthma. AB - We studied the clinical effect of a combination aerosol containing salbutamol and beclomethasone dipropionate in comparison to doubling the standard dose of salbutamol from an inhaler. Fifty-seven patients completed the double-blind, crossover study. They were treated with either an aerosol of 100 micrograms beclomethasone dipropionate and 200 micrograms salbutamol or 400 micrograms salbutamol alone. Both regimens were administered four times a day for 4 weeks. The patients showed significant improvement in FEV1, PEFR, and symptom scores after treatment with beclomethasone dipropionate and salbutamol compared with pre trial values and with treatment with double the dose of salbutamol. The patients demonstrated a clear preference for treatment with the combination of beclomethasone dipropionate and salbutamol. Regular treatment with beclomethasone dipropionate in addition to salbutamol as a combination inhaler provides much better control of asthma than merely increasing the dose of salbutamol in those patients poorly controlled on standard doses of inhaled bronchodilators. PMID- 2912328 TI - Mycobacteria and AIDS mortality. PMID- 2912327 TI - Recurrent swelling, abdominal pain, and vomiting in a 72-year-old male. PMID- 2912329 TI - Prostaglandin E1 in the adult respiratory distress syndrome. Benefit for pulmonary hypertension and cost for pulmonary gas exchange. AB - Prostaglandin E1 (PGE1) has been reported to improve survival in patients with the adult respiratory distress syndrome (ARDS). However, the effects of this pulmonary vasodilating compound on gas exchange have been little documented. We therefore measured hemodynamics, blood gases, and the distributions of ventilation-perfusion ratios (VA/Q), using the multiple inert gas elimination technique, at baseline and during infusion of PGE1 0.02 to 0.04 microgram.kg 1.min-1 in six patients with pulmonary hypertension secondary to ARDS ventilated with 10 cm H2O positive end-expiratory pressure. PGE1 decreased systemic arterial mean pressure (-16%) and pulmonary arterial mean pressure (-15%) and increased cardiac index (+20%) and heart rate (+11%). Arterial PO2 decreased from 99 +/- 6 to 77 +/- 8 mm Hg (p less than 0.01, mean +/- SEM) with no change in mixed venous PO2 and in O2 consumption. PGE1 increased true shunt from 21 +/- 4 to 32 +/- 5% of total blood flow (p less than 0.01) with no significant modification in the pattern of VA/Q distribution. Thus, in ARDS, pulmonary hypertension is reduced by PGE1 at the price of a deterioration in pulmonary gas exchange. The clinical relevance of these findings remains to be evaluated. PMID- 2912330 TI - Enhancement of hypoxic pulmonary vasoconstriction by low dose almitrine bismesylate in normal humans. AB - The effect of almitrine bismesylate on hypoxic pulmonary vasoconstriction (HPV) remains controversial. We therefore investigated in a double-blind, placebo controlled, randomized design the effects of low dose of almitrine bismesylate (4 micrograms/kg/min given intravenously) on blood gases, pulmonary hemodynamics, and ventilation-perfusion (VA/Q) distributions in normal subjects breathing a hypoxic mixture (FIO2, 0.125), room air (FIO2, 0.21), and oxygen (FIO2, 1.0) in a random sequence. In the placebo group (7 subjects), no change was recorded. In the almitrine group (10 subjects), arterial PO2 improved during hypoxia (from 42 +/- 2 to 47 +/- 1 mm Hg, p less than 0.05, mean +/- SEM) and normoxia (from 99 +/ 3 to 104 +/- 2, p less than 0.05). Pulmonary arterial mean pressure and pulmonary vascular resistance index increased with almitrine during hypoxia, respectively, from 20 +/- 1 to 23 +/- 1 mm Hg (p less than 0.01) and from 207 +/- 22 to 283 +/- 35 dyne.s.cm-5.m2 (p less than 0.01), and during normoxia, respectively, from 12 +/- 1 to 14 +/- 1 mm Hg (p less than 0.05) and from 90 +/- 11 to 137 +/- 13 dyne.s.cm-5.m2 (p less than 0.05). The VA/Q distribution improved during hypoxia, with a shift of the blood flow distribution to better oxygenated lung units with higher VA/Q ratios. We conclude that in normal humans low dose of almitrine improves gas exchange by an enhancement of HPV. PMID- 2912331 TI - Nifedipine reduces pulmonary pressure and vascular tone during short- but not long-term treatment of pulmonary hypertension in patients with chronic obstructive pulmonary disease. AB - We evaluated in patients suffering from COPD-related pulmonary hypertension whether nifedipine therapy lowers acutely and chronically pulmonary vascular pressure and resistance and whether pulmonary transmural pressure may be further lowered by the combined use of nifedipine and oxygen. Changes of the pulmonary vascular tone were determined on the pulmonary driving pressure/flow curve, which was generated by upright exercise. Fifteen patients with COPD and mean pulmonary pressure greater than or equal to 20 mm Hg were studied at control (Week 0) and after 1 wk of nifedipine treatment (180 mg daily, Week 1). It was possible to pursue the same nifedipine daily dosage for 2 months in 10 patients, who were re evaluated after 8 wk of treatment and after nifedipine withdrawal the following week. At Week 1, mean pulmonary transmural pressure was reduced (32.8 +/- 4.1 versus 27.3 +/- 2.8 mm Hg, mean +/- SE, p less than 0.05) via active pulmonary vasodilation because the pulmonary driving pressure/flow curve was shifted right and downward. Both mean transmural pulmonary pressure lowering effect and active pulmonary vasodilatation regressed during long-term nifedipine treatment. Oxygen reduced pulmonary transmural pressure (32.8 +/- 4.1 versus 28.6 +/- 2.9 mm Hg, p less than 0.05, Week 0); however, this effect always disappeared during nifedipine treatment. We conclude that nifedipine should not be used as long-term treatment for COPD-related pulmonary hypertension and that nifedipine inhibits the oxygen capability to reduce pulmonary pressure. PMID- 2912332 TI - Diltiazem, verapamil, and nifedipine inhibit theophylline-enhanced diaphragmatic contractility. AB - The ability of theophylline to limit diaphragmatic fatigue and to improve contractility appears to be dependent upon alterations in calcium metabolism. The mechanism responsible for these actions, however, remains unclear. We used perfused, contracting, intact rat diaphragm to measure the influence of therapeutic theophylline levels (10(-4) M) on tension development, in the presence or absence of the three most commonly used calcium channel blocking agents, or in the absence of calcium. Concentrations of diltiazem (10(-4) M), verapamil (10(-5) M), or nifedipine (10(-6) M) sufficient to completely block transmembrane calcium channels, were used. During the experiment, each diaphragm preparation was subjected to one of two fatiguing procedures: one to mimic that encountered during tachypnea and one to mimic that encountered during increased respiratory resistance. Our findings showed that therapeutic levels of theophylline were related to statistically significant (p less than 0.0005) increases in diaphragmatic contractility under control conditions and to statistically significant reductions in the sensitivity of the preparation to fatigue. All three calcium channel blockers negated the positive influence of theophylline. Zero calcium also prevented theophylline from enhancing the contractile properties of the diaphragm. It is our conclusion that theophylline enhances the contractile properties of the diaphragm by altering the transmembrane movement of calcium. Calcium antagonists, in turn, inhibit the beneficial effects of theophylline on diaphragm function. PMID- 2912333 TI - The bacteriology of bronchiectasis in Hong Kong investigated by protected catheter brush and bronchoalveolar lavage. AB - Bacteria often colonize the lower respiratory tract of patients with bronchiectasis. Although the role of these bacteria in the pathogenesis of the disease is uncertain, their accurate identification is important for epidemiologic and treatment purposes. Therefore, the aims of this study were: (1) to identify these bacteria in patients with bronchiectasis without cystic fibrosis using the protected catheter brush (PCB) in order to avoid oropharyngeal contamination, and (2) to compare the results of bronchoalveolar lavage (BAL) with PCB. Quantitative culture was performed on PCB and BAL specimens obtained from the most severely affected lobes of 23 patients with bronchiectasis. Results of PCB showed no significant growth (less than 10(3) colony-forming units [cfu]/ml) in nine patients and 17 significant isolates (greater than 10(3) cfu/ml) in the rest: H. influenzae, 5; P. aeruginosa, 4; K. ozaenae, 2; S. aureus, 2; P. fluorescens, 1; S. pneumoniae, 1; Veillonella, 1; and coag.-ve Staph., 1. For BAL, the results were the same (20 isolates) regardless of whether 10(4) or 10(5) cfu/ml was chosen as the cutoff point. More organisms were cultured from BAL specimens, and these included all but one of the organisms cultured from PCB. We conclude that the bacteriology of bronchiectasis in Hong Kong is different from that reported in sputum studies in the West (mainly H. influenzae, S. pneumoniae, and S. aureus), and with 10(4) cfu/ml as the cutoff point, BAL gives comparable results to PCB. PMID- 2912334 TI - Mechanism of rib cage inspiratory muscle recruitment in diaphragmatic paralysis. AB - Paralysis of the diaphragm promotes an increase in the activation of the rib cage inspiratory muscles, and previous studies have suggested that this compensation is primarily due to vagal mechanisms (6). To test this hypothesis, we have assessed the effect of diaphragmatic paralysis on the electrical response of 19 parasternal intercostal muscles in eight anesthetized, vagotomized, spontaneously breathing dogs in the supine posture. Complete diaphragmatic paralysis was induced by section of the C5, C6, and C7 phrenic nerve roots in the neck. With the animals breathing room air, diaphragmatic paralysis resulted in a mean 94% increase in the peak height of integrated parasternal activity (p less than 0.001) associated with a 14 mm Hg decrease in arterial PO2 (p less than 0.05) and an 8 mm Hg increase in arterial PCO2 (p less than 0.001). The augmented parasternal activity was unrelated to the duration of inspiration and persisted when the animals were given a hyperoxic gas mixture. Thus the rib cage inspiratory muscles still compensate for diaphragmatic paralysis in the absence of vagal signals and of hypoxemia. This compensation probably results from the considerably augmented CO2 load placed on the extradiaphragmatic muscles. PMID- 2912335 TI - Voluntary versus reflex regulation of maximal exercise flow: volume loops. AB - We determined the efficiency with which maximal exercise ventilatory output could be mimicked voluntarily. Five normal subjects exercised to maximal volitional effort and flow:volume and pressure:volume loops, and end-expiratory lung volume (EELV) and breathing pattern were measured. All subjects increased expiratory flow rate and reduced EELV sufficiently so that the forced vital capacity loop was approximated during at least some portion of expiration, but the generation of pleural pressure remained effective, i.e., equal to or only slightly in excess of that required to produce maximal expiratory flow (Pmax). Subsequently, while at rest, subjects used visual feedback and were able to closely mimic the flow:volume, EELV, and breath-timing achieved in maximal exercise; however: (1) expiratory pressures were excessive and usually exceeded average Pmax; (2) abdominal expiratory muscle activity was increased, as indicated by positive shifts in expiratory gastric pressure; and (3) total ventilatory work was increased 15 to 40% greater than that achieved in maximal exercise. Maximal voluntary efforts (MVV) caused EELV to increase and ventilatory work was increased 20 to 300% greater than during maximal exercise. We conclude that accurate determination of maximal effective ventilatory output available for maximal exercise or precise quantitation of the metabolic cost of producing maximal exercise ventilation requires replication of the pressure:volume, breath timing, and EELV characteristics achieved in maximal exercise. PMID- 2912336 TI - Long-term follow-up of symptoms, pulmonary function, respiratory muscle strength, and exercise performance after botulism. AB - Respiratory muscle weakness occurs commonly at presentation in patients with botulism. Although clinical improvement occurs over several months, symptoms such as fatigue and dyspnea persist in many patients in the long term. To determine whether continued respiratory muscle weakness might contribute to these symptoms, we compared lung function tests, respiratory muscle strength, and exercise performance in 13 patients 2 years after type B botulism. We found that residual symptoms including dyspnea and fatigue were common in botulism patients at 2 years postintoxication. Lung function tests had returned to normal in all patients. Maximal inspiratory and expiratory pressures were similar between botulism patients and control subjects. Evaluation of individual results showed evidence of inspiratory muscle weakness in four of 13 patients with botulism (Plmax less than 65% predicted). Maximal oxygen consumption and maximal workload during exercise were reduced in botulism patients in comparison to control subjects. During exercise, botulism patients had a more rapid and shallow breathing pattern and a higher dyspnea score at a given minute ventilation in comparison to control subjects. Reasons for premature exercise termination in botulism patients were multifactorial. Although respiratory muscle weakness may have been contributory in some patients, most appeared to be limited by reduced cardiovascular fitness, leg fatigue, or reduced motivation. PMID- 2912337 TI - Effect of salicylate on upper airway dilating muscles in anesthetized dogs. AB - It is well documented that salicylate given in large doses stimulates ventilation. As increased ventilatory drive is often associated with augmented upper airway dilating muscle activity, we evaluated in anesthetized dogs the effect of salicylate on the electrical activity of three upper airway muscles, the alae nasi, the genioglossus, and the posterior cricoarytenoid. The electromyograms of these muscles were compared with those of the diaphragm before and at 15-min intervals after intravenous salicylate administration (250 mg/kg). Salicylate induced a gradual increase in ventilation and in the electrical activity of all muscles examined (p less than 0.001). Compared to baseline activity, salicylate increased the electrical activity of the genioglossus more than that of the diaphragm (p less than 0.01). The increase in upper airway muscle activity was observed also in vagotomized dogs, and was not accounted for by changes in arterial blood gases or pH. Increases in upper airway muscle electrical activity were associated with a significant decrease in upper airway resistance to airflow (mean reduction of 62 +/- 7% SE, p less than 0.01). The preferential increase in genioglossus electrical activity and the decrease in upper airway resistance observed in this study with salicylate suggest that salicylate, and possibly other pharmacologic agents that stimulate ventilation, may improve upper airway patency. PMID- 2912338 TI - Spirometric abnormalities in young smokers correlate with increased chemiluminescence responses of activated blood phagocytes. AB - Spirometric values determined from the flow-volume loops of 60 healthy young smokers (mean age, 28 +/- 0.6 yr) were correlated with measurements of the release of extracellular and intracellular reactive oxidants (RO) as determined by luminol-enhanced chemiluminescence (LECL) from peripheral blood activated with the synthetic chemotactic tripeptide FMLP combined with cytochalasin B (CB). Fractionation and reconstitution experiments revealed that LECL originated predominantly from polymorphonuclear leukocytes (PMNL). Circulating total leukocyte counts and serum thiocyanate levels were also determined. The data were analyzed using Spearman's correlation coefficient and by multiple regression analysis. Cigarette smoking was associated with elevated intracellular and especially extracellular LECL responses, the latter being strongly correlated (p less than 0.0001) with cigarettes smoked per day, serum thiocyanate levels, circulating leukocytes, and PMNL counts. Abnormalities of the spirometric parameters FEV1/FVC, FEF50/FVC, FEF25, FEF25-75, and FEF75-85 correlated best with extracellular LECL (p less than 0.0002 to p less than 0.0001), but also with pack-years (p less than 0.006 to p less than 0.0001), cigarettes smoked per day (p less than 0.008 to p less than 0.0002), thiocyanate levels (p less than 0.04 to p less than 0.002) and leukocyte counts (p less than 0.03 to p less than 0.002). According to stepwise multiple regression analysis of the data the combination of the independent variables extracellular LECL, pack-years, and numbers of circulating PMNL accounts for 35.6% of the variation in lung function in the group of cigarette smokers, with LECL being the most important contributor (26%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2912339 TI - Effect of inhaled leukotriene C4 on cardiopulmonary function. AB - The changes in transcutaneous oxygen saturation (SaO2%) and airway responses to inhaled histamine and leukotriene C4 (LTC4) were examined in 10 asthmatic patients, and the effect of inhaled LTC4 (16 nmol) on cardiopulmonary hemodynamics was examined in seven nonasthmatic patients undergoing diagnostic cardiac catheterization. In asthmatic patients, LTC4 produced oxygen desaturation on two occasions. At a lower dose (2.0 nmol) LTC4 produced a marked fall in SaO2% that lasted less than 15 min and occurred in the absence of significant bronchoconstriction as measured by changes in FEV1, FEF25-75, and SGaw. At a higher cumulative dose (7 nmol), LTC4 caused prolonged oxygen desaturation with slow recovery and this was associated with significant bronchoconstriction. In contrast, histamine inhalation produced a single response with a fall in both FEV1 and SaO2% of short duration. The dose-response characteristics of LTC4 and histamine on oxygen desaturation in asthmatic patients appear to differ significantly and probably are dependent on relative sensitivities of pulmonary vascular and bronchial smooth muscle to these agonists. A single inhaled dose of LTC4 in nonasthmatic subjects produced a marked drop in PaO2 with significant increase in AaPO2, and this was associated with a mean (SEM) decrease in FEV1 of 14% (2.5) from the baseline. The mean cardiac output fell by 15% (3.4) without significant changes in blood pressure and heart rate. There was no electrocardiographic evidence of myocardial ischemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2912340 TI - Association of cigarette smoking with decreased numbers of circulating natural killer cells. AB - To investigate the relationship between cigarette smoking and the level of circulating natural killer (NK) cells, we studied 282 subjects from a population based, stratified random sample of healthy persons. NK cells were enumerated by flow cytometry using the monoclonal antibody anti-Leu 11A. Cigarette smokers had a significantly lower proportion of NK cells than did subjects who had never smoked (5.5 +/- 0.3% versus 7.4 +/- 0.4% of lymphoid cells; p = 0.0002). NK cells were also decreased among ex-smokers (5.6 +/- 0.4%; p = 0.002), including subjects who had not smoked for more than 20 yr. The white blood cell and lymphocyte counts were increased in smokers compared with those in never smokers (p less than 0.0001). In contrast to NK cells, the smoking-related changes in leukocyte count were not present in ex-smokers, even those who had stopped smoking within the past year. Multivariate analysis confirmed that both current and past smokers had significant decreases in both the number and proportion of NK cells after controlling for age, sex, and lymphocyte count. These data indicate that cigarette smoking is associated with a decrease in the number and proportion of circulating NK cells, and that this effect is present many years after smoking cessation. This quantitative NK cell deficit may contribute to the elevated risk of malignancy in this population. PMID- 2912341 TI - Biosynthesis of the third and fifth complement components by isolated human lung cells. AB - Increasing research efforts have been directed at determining the contribution of locally synthesized (cell-derived) complement in host defense and inflammation. In the studies presented here, we determined the ability of a continuous cell line of type II pneumocytes (A549) and a cell line of human lung fibroblasts (WI 38) to produce complement components in vitro. Complement biosynthesis by A549 pneumocytes and WI-38 fibroblasts was demonstrated by incorporation of [35S]methionine into immunoprecipitable complement proteins. Using this technique, A549 pneumocytes were demonstrated to synthesize Clr, Cls, C4, C3, C5, C6, C7, C8, C9, Factor B, Factor H, Factor I, and C1s inactivator. In comparison, WI-38 fibroblasts were shown to synthesize Cls, C4, C3, C5, C6, C8, and C9. Because previous work has demonstrated the central role of C3, C5, and their activation products in regulating lung inflammation and tissue injury, we further investigated the production of C3 and C5 by both lung pneumocytes and fibroblasts using enzyme-linked immunospecific assays. A549 cells cultured in the presence of 15% fetal bovine serum (FBS) produced antigenic C3 (135 ng C3/ml/24 h) at a greater rate than did identical cells maintained in serum-free culture conditions (70 ng C3/ml/24 h). Similarly, antigenic C5 production by A549 pneumocytes was greatest in the presence of FBS when compared with cells maintained in serum-free culture conditions (245 ng C5/ml/24 h versus 155 ng C5/ml/24 h).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2912342 TI - Alveolar macrophage proliferation in situ after thoracic irradiation of rats. AB - Saline lavage was performed on rat lungs at weekly intervals for as long as 6 wk after thoracic irradiation (24 Gy). The number of alveolar macrophages recovered by lavage was significantly increased compared with that in control animals beginning at 4 wk after irradiation (p less than 0.05). Autoradiographic analysis of macrophages recovered demonstrated an increased labeling index compared with that in control animals beginning 3 wk after irradiation (p less than 0.05). Macrophage proliferation in vivo was also assessed by injecting rats with vincristine and evaluating macrophages recovered by lung lavage for arrested mitoses. The number of arrested mitoses noted was significantly increased in rats at 4 wk after irradiation compared with that in control animals (p less than 0.05). These data indicate that after high dose thoracic irradiation there is an expansion of the alveolar macrophage population that is due at least in part to increased local proliferation of alveolar macrophages. PMID- 2912343 TI - A 16-month study of the development of genetic emphysema in tight-skin mice. AB - The tight-skin (tsk) mouse has been recently proposed as a model of genetically determined emphysema. In the present study, the development of this lung lesion was investigated morphometrically in both male and female tsk mice from 4 days to 16 months of age. "Pallid" (pa) mice with a closely related genetic background served as controls. Despite small differences in the mean linear intercept seen at 1 and at 16 months, both male and female tsk mice were found to be similarly susceptible to the development of the emphysematous lesion. Three main phases were observed in the evolution of the emphysema. The first phase, from 4 days to 2 months after birth, included enlargement of the peripheral lung units, already evident at 4 and at 15 days, and destruction of the lung parenchyma, which occurred between 15 days and 1 month and rapidly progressed for as long as 2 months. A second phase of stabilization or of mild progression of the emphysematous lesion occurred between 2 and 8 months of age. A third phase, in the advanced age between 8 and 16 months, included a further exacerbation of the parenchymal destruction. At 16 months of age, the lungs of the pa mice also showed some patchy areas of air-space enlargement with destruction of the alveolar septa. PMID- 2912344 TI - Long-term follow-up of drug abusers with intravenous talcosis. AB - Six patients who injected talc containing drugs intended for oral use were assessed over a period of ten or more years from the time of initiation of this habit. Despite discontinuation of the drug abuse, all developed severe respiratory disability and three died from their disease. An evolving spectrum of roentgenographic and functional patterns is considered to be virtually diagnostic of this disorder. Roentgenographically, an initial diffuse, pin-point micronodularity subsequently becomes associated with conglomerates, usually in the upper lobes, closely resembling the progressive massive fibrosis (PMF) of the pneumoconioses. The lower lobes, on the other hand, become relatively translucent, in some instances with bulla formation and the development of pneumothorax. Pulmonary function, initially with both restrictive and obstructive features, eventually becomes markedly obstructive with hyperinflation and air trapping. At this late stage, pathologic examination reveals emphysema in addition to the granulomatous inflammation and fibrosis surrounding the talc particles in the pulmonary interstitium. PMID- 2912345 TI - The mechanics of airway narrowing in asthma. AB - This study was designed to determine the potential importance of airway wall thickening in the pathogenesis of the excess airways narrowing of asthma. The airways in postmortem specimens of lung obtained from 18 patients who suffered from asthma were compared to similar airways from 23 patients without asthma. Each airway was projected onto a digitizing board of a microcomputer to trace the internal and external perimeter of the airway and to calculate the submucosal and mucosal thicknesses. The relaxed length of the airway smooth muscle and the shortening required to occlude the airway lumen were calculated. These data show that the wall area was greater (p less than 0.001) in the membranous and cartilaginous airways of asthmatic patients and the airway smooth muscle shortening required to occlude the lumen was less in asthmatic than nonasthmatic airways (p less than 0.001). The increased wall area was due to increased areas of epithelium, muscle, and submucosa. We conclude that the walls of the airways of patients with asthma are thickened by chronic inflammation and that this thickening could be as important as smooth muscle shortening in determining the airway responsiveness of these patients. PMID- 2912346 TI - Provocation test coupled with bronchoalveolar lavage in diagnosis of propranolol induced hypersensitivity pneumonitis. AB - A 59-yr-old man was given over a 30-month period a cumulative dose of 36 g of propranolol for treatment of angina pectoris. He then presented with respiratory disease, having all the clinical, radiologic, and functional characteristics of interstitial pneumonitis. No other cause of pneumonitis was found. Bronchoalveolar lavage (BAL) showed a lymphocytic alveolitis with lymphocyte subset inverted ratio. After a 9-wk period of drug withdrawal, clinical and radiologic improvement was observed along with resolution of BAL abnormalities. Propranolol therapy was resumed for 6 wk and induced the recurrence of BAL abnormalities. Propranolol treatment was finally stopped, and 15 wk later, clinical symptoms abated, chest roentgenogram and pulmonary function tests were improved, and BAL data returned to normal. This observation seems to exemplify the possible diagnostic value of coupling provocation test with BAL cell data in some hypersensitivity pneumonitis induced by drugs. In addition, these data support the role of a cell-mediated immunologic mechanism in the pathogenesis of propranolol-induced pneumonitis. PMID- 2912347 TI - Acute eosinophilic pneumonia: a hypersensitivity phenomenon? AB - A previously healthy young man presented with acute respiratory distress and diffuse bilateral infiltrates on chest radiograph. Eosinophilic pneumonia was diagnosed by bronchoalveolar lavage and confirmed by transbronchial lung biopsy. There was no evidence of an infectious etiology, and the patient rapidly improved with corticosteroid therapy. Most cases of eosinophilic pneumonia reported previously have followed a chronic course. The case presented here was acute in onset, suggesting a hypersensitivity reaction. High levels of bronchoalveolar lavage eosinophils indicate the diagnosis but not the etiology of eosinophilic pneumonia. PMID- 2912348 TI - Cavitary pulmonary metastases in angiosarcoma. Diagnosis by transthoracic needle aspiration. AB - An unusual case of cavitary pulmonary metastases from an angiosarcoma of the scalp is described. Transthoracic needle aspiration biopsy of one of the cavitary nodules was successful in establishing the diagnosis. PMID- 2912349 TI - Maximal static respiratory pressures in the normal elderly. AB - To determine if a relationship exists between maximal static respiratory pressures measured at the mouth and age greater than 55 yr, and if so, whether regression equations can be derived that accurately reflect this, we measured maximal inspiratory (Plmax) and expiratory (PEmax) pressures in 64 normal women and 40 normal men older than 55 yr of age. We found no relationship between PImax and PEmax and age greater than 55 yr (all r squared values less than 0.14). We tested the reproducibility of our measurements of PImax and PEmax in 13 and 12 subjects, respectively, on three separate occasions. Repeated measures analysis showed no significant differences in these measurements. Using the measurements obtained in this large study, we calculated 95% confidence limits for PImax and PEmax values in men and women older than 55 yr of age. The 95% confidence limits for PImax in men were 55 to 161 cm H2O, and 26 to 124 cm H2O in women. The 95% confidence limits for PEmax in men were 90 to 256 cm H2O, and 46 to 184 cm H2O in women. We conclude that given the large interindividual variation, a cross sectional study such as this or other previous studies may not be able to reveal age-dependent changes unless very large numbers are used, and even then potential for bias exists. However, with the small intraindividual coefficients of variation in repeated measurements of PImax and PEmax, a longitudinal study may provide more pertinent information. PMID- 2912350 TI - Lymphocyte populations in lung tissue, bronchoalveolar lavage fluid, and peripheral blood in rats at various times during the development of silicosis. AB - Inflammatory cells and lymphocyte populations were examined in the bronchoalveolar lavage (BAL) fluid, lung tissues, and peripheral blood from rats at various times after the intratracheal instillation of silica. In lavage fluid, there was a rapid initial increase in the percentage and number of polymorphonuclear leukocytes (PMN), which slowly decreased during the course of the experiment. In addition, compared to controls, there was an increased number and percentage of lymphocytes throughout the 75 days of the experiment. The lymphocytic populations, which were determined by an indirect immunofluorescence method with monoclonal antibodies to lymphocyte surface markers, showed a predominance of the T-helper phenotype from Day 14 through the end of the experiment (Day 75). The number of PMNs obtained from collagenase digest of the lung was increased over control levels up to Day 7 after silica administration and remained at a relatively constant level until Day 14, after which time they decreased slightly in number. The total number of lymphocytes peaked on Day 14, with cells of the T-helper phenotype predominating after this time. In the peripheral blood, T-helper cells from silicotic rats were significantly increased over control rats on Days 7 and 14 but returned to normal control values after this time. The lymphocyte subsets in the BAL, but not in the peripheral blood, more closely reflect the lymphocyte patterns in the lung. The results of these experiments suggest that T-helper cells may play an important role in the inflammatory-fibrotic events in the lungs of rats with silicosis. PMID- 2912351 TI - Glasnost and communication. PMID- 2912352 TI - The effects of controlled oxygen therapy on ventricular function in patients with stable and decompensated cor pulmonale. PMID- 2912353 TI - Worsening oxygenation in the mechanically ventilated patient. PMID- 2912354 TI - Bronchoalveolar lavage cell and lymphocyte phenotype profiles in healthy asbestos exposed shipyard workers. AB - The cellular and lymphocyte phenotypic composition of bronchoalveolar lavage (BAL) fluid and peripheral blood (PB) from 15 healthy, nonsmoking, asbestos exposed shipyard workers (AEW) and 10 nonsmoking, age-matched unexposed workers (UEW) were compared. None of the AEW had clinical, radiographic, or physiologic evidence of asbestosis, but six had radiographic evidence of pleural plaques and/or thickening. The mean duration of asbestos exposure was 16.3 +/- 2.3 yr, and the mean period since exposure was 10.8 +/- 0.5 yr. All but three of the AEW and none of the UEW had asbestos bodies detected in the first 20 ml of BAL fluid recovered (0.1 to 35 asbestos bodies/ml). The AEW had a significantly higher mean percentage (19.1 +/- 2.8% versus 9.7 +/- 1.6%) and concentration (31.6 +/- 5.2 x 10(3) cells/ml versus 14.7 +/- 2.5 x 10(3) cells/ml) of BAL lymphocytes compared with that in the UEW, with an increased mean concentration of each phenotype measured. In PB, the mean lymphocyte concentration was also higher in the AEW than in the UEW (2.0 +/- 0.3 x 10(3) cells/ml versus 1.5 +/- 0.3 x 10(3) cells/ml), but the difference was not statistically significant, and there was no increase of any phenotype measured. BAL lymphocytosis did not correlate with exposure history or BAL asbestos body count, but was greater in AEW with pleural abnormality (30.1 +/- 2.9% versus 11.8 +/- 1.6%). BAL concentrations of CD-20, CD 3, and CD-4, but not of CD-8 cells were significantly increased compared with those in the AEW without pleural abnormality. Further longitudinal studies are needed to determine the prognostic significance of these findings. PMID- 2912355 TI - The epidemiology of disseminated nontuberculous mycobacterial infection in the acquired immunodeficiency syndrome (AIDS). AB - We analyzed cases of disseminated nontuberculous mycobacterial infection (DNTM) in patients with AIDS reported to the Centers for Disease Control. Between 1981 and 1987, 2,269 cases were reported. In 96% of cases, infection was caused by M. avium complex (MAC). The number of cases has risen steadily since 1981, but the rate as a percentage of AIDS cases has remained stable at 5.5%. DNTM was seen less frequently in AIDS cases with Kaposi's sarcoma than in other AIDS cases (p less than 0.01). Rates of DNTM were lower in Hispanics and declined with age but were not significantly different by patient sex or means of acquiring HIV infection. Rates of disseminated MAC varied by geographic region from 3.9% to 7.8% (p less than 0.0001). As assessed by helper/suppressor T-cell ratios, AIDS patients with DNTM were not more immunologically impaired than those with other opportunistic infections. Life table analysis revealed that AIDS patients with DNTM survived a shorter time (median, 7.4 months) than did other AIDS patients (median, 13.3 months; p less than 0.0001). We conclude that DNTM is acquired by unpreventable environmental exposures. Because DNTM adversely affects survival of AIDS patients, effective therapeutic agents must be vigorously sought. PMID- 2912356 TI - Can mild bronchospasm reduce gastroesophageal reflux? AB - During attacks of asthma, changes in the transdiaphragmatic pressure gradient may impair the antireflux barrier and provoke gastroesophageal reflux (GER). If GER triggers asthma and asthma causes GER, a vicious circle could arise with an increase in the severity of asthma symptoms. The aim of this investigation was to determine whether postprandial reflux in asthmatics with GER disease is increased during histamine-induced bronchospasm and also if theophylline increases GER during provoked episodes of bronchospasm. Ten patients with chronic asthma and pathologic GER were challenged with either histamine or saline in randomized order with and without their regular dose of oral slow-release theophylline. FEV1 was recorded at regular intervals during the hour of provocation, and acid reflux (pH less than 4) was monitored by antimony pH electrodes in the esophagus. GER was not more pronounced during the provoked bronchospasm period irrespective of theophylline treatment or not. It seems unlikely that mild bronchospasm provokes reflux in patients with asthma and GER. It would appear that mild bronchospasm is rather protective against gastroesophageal reflux. PMID- 2912358 TI - Response of normal infants to inhaled histamine. AB - The age at which nonspecific bronchial hyperresponsiveness (BHR) is first seen in humans is unknown, though both genetic and environmental factors have been implicated in its development. The current study aimed to establish whether BHR to histamine can be demonstrated in normal infants. Twelve infants, mean age of 7.8 months (range, 3 to 18 months), were studied. None had any history of a previous significant respiratory illness. Respiratory function was monitored using the maximal flow at function residual capacity (VmaxFRC) obtained with the forced expiratory flow-volume technique. Histamine was inhaled in doubling concentrations from 0.125 to 8 g.L-1. A greater than 30% fall in VmaxFRC was considered a response. All infants responded to histamine, the geometric mean concentration for their response being 1.4 g.L-1. Associated transient changes for the group were an increase in respiratory rate (p less than 0.02) and a fall in SaO2 (p less than 0.001). Forced expiratory flow-volume curves were concave in all infants after the last dose of histamine. We speculate that humans are born with "bronchial hyperresponsiveness" and that genetic or environmental factors determine which infants lose it thereafter. PMID- 2912359 TI - Screening for endometrial cancer: is it effective? PMID- 2912357 TI - Short-term pulmonary function change in association with ozone levels. AB - As part of the ongoing Harvard Six Cities study of the respiratory effects of air pollution, repeated measurements of pulmonary function (FVC, FEV75, MMEF, and Vmax75) were taken at approximately weekly intervals in a population of 154 school children living in Kingston and Harriman, Tennessee. A series of as many as six measurements were obtained for each child over approximately a 2-month period beginning in February 1981. Concurrent measurements of ambient ozone, and fine particle and fine sulfate concentrations were obtained at a site near the study community. The maximal hourly ozone concentration observed during the study was 78 ppb. Child-specific linear regressions were fit that related short-term pulmonary function changes to air pollution or temperature. We found that decrements in FVC, FEV75, MMEF, and Vmax75 were associated with ozone, but not with particulate levels. Decrements in FVC, MMEF, and Vmax75 were also associated with temperature. Although slopes of pulmonary function on ozone varied across children, in general there was no evidence that this variation represented heterogeneity of response as opposed to random estimation errors. In addition, no evidence was found that individual response to ozone was related to sex, presence of asthma, respiratory illness before 2 yr of age, or the MMEF/FVC ratio, a rough surrogate for airway size. We conclude that ambient exposures to ozone at levels well below the National Ambient Air Quality Standard of 120 ppb are associated with transient decreases in lung function, the long-term significance of which is uncertain. PMID- 2912360 TI - Increased lung water and ascites after massive cocaine overdosage in mice and improved survival related to beta-adrenergic blockage. AB - STUDY OBJECTIVE: To determine the effect of massive cocaine intoxication on lung water and ascites accumulation and the effect of beta- and alpha-adrenergic blockade on survival in massive cocaine intoxication in the mouse. DESIGN: The effect of massive cocaine intoxication on lung water, ascitic fluid accumulation, and survival following LD 100 doses of intravenous cocaine with and without alpha and beta-adrenergic blockade was determined. INTERVENTIONS: Cocaine hydrochloride (0.15 mg/g body weight) was administered intravenously with no other interventions; with propranolol hydrochloride intravenously (0.5 mg per mouse) before and after cocaine; and with phentolamine intravenously (10.5 micrograms per mouse) before cocaine. MEASUREMENTS AND MAIN RESULTS: Intravenous cocaine hydrochloride resulted in an increase in lung water (saline controls, 4.17 +/- 1.3 [standard deviation] mg water per g mouse; cocaine hydrochloride, 5.94 +/- 0.9 mg water per g mouse; P less than 0.002). Cocaine hydrochloride always resulted in the accumulation of transudative ascitic fluid (saline controls, no measurable ascitic fluid; cocaine administration, 20.2 +/- 12.9 micrograms per mouse; ascitic fluid protein concentration, 23.5 +/- 8.5 g/L). Propranolol hydrochloride administered before or after intravenous cocaine hydrochloride resulted in a striking reduction in mortality (84 of 84 mice without propranolol died [mortality = 100%]; 7 of 39 mice with propranolol died [mortality = 18%]; P less than 0.001). CONCLUSIONS: Massive cocaine intoxication is associated with increased lung water and transudative ascites. Fluid accumulation is not prevented by either alpha- or beta-adrenergic blockers. Propranolol, administered either before or after cocaine, sharply reduces mortality. The results should be extrapolated to treatment in humans with caution. PMID- 2912361 TI - Low-density lipoprotein (LDL) distribution shown by 99mtechnetium-LDL imaging in patients with myeloproliferative diseases. AB - STUDY OBJECTIVE: To image and identify by noninvasive methods the sites of low density lipoprotein (LDL) catabolism in patients with myeloproliferative disease in whom chronic hypocholesterolemia was previously reported. STUDY DESIGN: The 99mTechnetium-LDL (Tc-LDL) distribution in patients with myeloproliferative diseases was compared with that in normal subjects. The Tc-LDL distribution was also compared with the distribution and organ uptake of a macrophage-seeking radiotracer. 99mTc-sulfur colloid (Tc-SC). SETTING: Major metropolitan referral center and institutional practice. PATIENTS: Three normal subjects, two patients with polycythemia vera, two with post polycythemia myeloid metaplasia, and one with agnogenic myeloid metaplasia. The patients were being managed with hydroxyurea or phlebotomy. INTERVENTION: Ten mCi of Tc-LDL (homologous) was injected intravenously. MEASUREMENTS AND MAIN RESULTS: Gamma camera images of Tc LDL biodistribution and organ uptake were obtained 4 hours after injection of the tracer. In normal subjects, the Tc-LDL was predominantly taken up by the liver, with relative nonvisualization of spleen and central or peripheral marrow. Patients with myeloproliferative disease showed marked splenic uptake of Tc-LDL. Peripheral bone marrow uptake extended to the lower tibia in two patients with post-polycythemia myeloid metaplasia. Splenic and bone marrow uptake paralleled that of Tc-SC. Hypercellularity of central and peripheral marrow at the sites of Tc-LDL uptake was confirmed by biopsy specimens. The Tc-LDL uptake, however, was not correlated with collagen fibrosis. CONCLUSIONS: These results indicate that spleen and bone marrow are sites of LDL catabolism in patients with myeloproliferative disease and suggest the role of macrophages in the hypocholesterolemia and accelerated LDL catabolism of myeloproliferative disease. PMID- 2912362 TI - Chronic lymphocytic leukemia: recommendations for diagnosis, staging, and response criteria. International Workshop on Chronic Lymphocytic Leukemia. PMID- 2912363 TI - Fatal delayed hemolytic transfusion reaction without previous blood transfusion. PMID- 2912364 TI - The sand-trap hazard in magnetic resonance imaging. PMID- 2912365 TI - Upper gastrointestinal endoscopy. PMID- 2912366 TI - Nonsteroidal anti-inflammatory drugs and peptic ulcer. PMID- 2912368 TI - Nomenclature for pulmonary findings. PMID- 2912367 TI - Better housestaff schedules. PMID- 2912369 TI - Correction: Gastric function in the acquired immunodeficiency syndrome (AIDS) PMID- 2912370 TI - Selective induction of heme oxygenase-1 isozyme in rat testis by human chorionic gonadotropin. AB - A radioimmunoassay was developed to assess the response of testicular HO-1 to agents known to increase the microsomal heme oxygenase activity. Treatment of rats with human chorionic gonadotropin (hCG) increased the microsomal heme oxygenase activity in rat testis. The following data suggest that the increase was specific to the HO-1 isozyme: (a) The elution profile of heme oxygenase activity from a DEAE-Sephacel column showed an increase in the HO-1 peak, but not in the HO-2 peak, (b) the Western immunoblot of the testis microsomes showed an increase in HO-1 protein, and (c) the amount of HO-1 protein that was present in the microsomes, when measured by radioimmunoassay, was doubled. Using radioimmunoassay, it was shown that other agents known to increase the testicular heme oxygenase, sodium arsenate and sodium arsenite, also increased the microsomal content of HO-1. An inhibitor of the testicular microsomal heme oxygenase activity, cadmium, also increased the microsomal HO-1 protein. The findings suggest that inducibility of HO-1 extends to tissues other than the liver, in this instance, the testis, and further support the possibility that HO 1 is the only inducible form of heme oxygenase. PMID- 2912371 TI - Uridine-5'-phosphate synthase: evidence for substrate cycling involving this bifunctional protein. AB - Uridine 5'-phosphate (UMP) synthase contains two sequential catalytic activities for the synthesis of orotidine 5'-phosphate (OMP) from orotate (EC 2.4.2.10, orotate phosphoribosyltransferase) and the decarboxylation of OMP to form UMP (EC 4.1.1.23, OMP decarboxylase). Previous kinetic studies had indicated that partial channeling of OMP might occur [T.W. Traut and M.E. Jones (1977) J. Biol. Chem. 252, 8374-8381]; in the presence of a nucleotidase, there was no measurable formation of orotidine from OMP under conditions where OMP was maintained at a steady-state concentration [T.W. Traut (1980) Arch. Biochem. Biophys. 200, 590 594]. Recently claims were made that (i) the steady-state activities of UMP synthase could be modeled by Michaelis-Menten kinetics, and (ii) the nucleotidase activity in Ehrlich ascites cells was insufficient to degrade any significant amount of OMP [R.W. McClard and K.M. Shokat (1987) Biochemistry 26, 3378-3384]. The present studies show that UMP synthase has cooperative kinetics toward OMP, and that a substrate cycle involving orotate phosphoribosyltransferase, cytoplasmic nucleotidase, and uridine phosphorylase maintains the cyclic interconversion: orotate----OMP----orotidine----orotate, etc. It is therefore the complex steady-state kinetics of UMP synthase in the presence of OMP, and the existence of a substrate cycle that account for the results which were interpreted as channeling in the earlier studies. PMID- 2912372 TI - Menstrual cycle-associated alteration of sulfogalactosylceramide in human uterine endometrium: possible induction of glycolipid sulfation by sex steroid hormones. AB - The human uterine endometrium is a tissue in which cell proliferation and differentiation are strictly controlled by sex steroid hormones, and these hormone-controlled cellular events occurring in association with the menstrual cycle of the uterine endometrium should be accompanied by characteristic molecular and metabolic changes. To characterize the menstrual cycle at the molecular level, we analyzed the glycolipids of human uterine endometrium in the proliferative and secretory phases of the menstrual cycle. Neutral glycosphingolipids from uterine endometrium comprised globo-series glycosphingolipids, such as GlcCer, LacCer, Gb3Cer, and Gb4Cer, and the relative concentrations remained constant in the two phases. However, in the case of acidic glycosphingolipids, although the concentrations of sialoglycosphingolipids remained at constant levels in the two phases, sulfatide, I3-SulfoGalCer, dramatically increased from the proliferative to the secretory phase, amounting to 7-17 nmol/g dry weight in the proliferative phase and 115-245 nmol/g dry weight in the secretory phase. Since sulfatide was the only glycolipid that changed in association with the menstrual cycle, it is likely that the sulfotransferase responsible for the synthesis of sulfatide might be induced by sex steroid hormones, estrogen and progesterone, and that sulfatide might play an essential biological role in the secretory phase of the menstrual cycle in the uterine endometrium. PMID- 2912373 TI - Methoxyflurane acts at the substrate binding site of cytochrome P450 LM2 to induce a dependence on cytochrome b5. AB - Rabbit cytochrome P450 isozyme 2 requires cytochrome b5 to metabolize the volatile anesthetic methoxyflurane but not the substrate benzphetamine [E. Canova Davis and L. Waskell (1984) J. Biol. Chem. 259, 2541-2546]. To determine whether the requirement for cytochrome b5 for methoxyflurane oxidation is mediated by an allosteric effect on cytochrome P450 LM2 or cytochrome P450 reductase, we have investigated whether this anesthetic can induce a role for cytochrome b5 in benzphetamine metabolism. Using rabbit liver microsomes and antibodies raised in guinea pigs against rabbit cytochrome b5, we found that methoxyflurane did not create a cytochrome b5 requirement for benzphetamine metabolism. Methoxyflurane also failed to induce a role for cytochrome b5 in benzphetamine metabolism in the purified, reconstituted mixed function oxidase system. Studies of the reaction kinetics established that in the absence of cytochrome b5, methoxyflurane and benzphetamine are competitive inhibitors, and that in the presence of cytochrome b5, benzphetamine and methoxyflurane are two alternate substrates in competition for a single site on the same enzyme. These results all indicate that the methoxyflurane-induced cytochrome b5 dependence of the mixed function oxidase cytochrome P450 LM2 system is a direct result of the interaction between methoxyflurane and the substrate binding site of cytochrome P450 LM2 and suggest the focus of future studies of this question. PMID- 2912374 TI - Heart mitochondrial creatine kinase revisited: the outer mitochondrial membrane is not important for coupling of phosphocreatine production to oxidative phosphorylation. AB - The state of mitochondrial creatine kinase (CKmi-mi) in intact dog heart mitochondria and mitoplasts and the mechanism of its functional coupling with the oxidative phosphorylation system have been reinvestigated under different osmotic conditions and ionic compositions of the medium. It has been established that in a medium which mimics the cardiac cell cytoplasma, dissociation of CKmi-mi from the membrane of mitoplasts increases when the mitoplasts are swollen due to hypoosmotic treatment. It was shown by EPR that hypoosmotic treatment results in the enhancement of the mobility of phospholipids in the membrane bilayer. It has been also shown that when CKmi-mi is detached from the inner membrane in intact mitochondria in isotonic KCl solution, the effects of the coupling between CKmi mi and oxidative phosphorylation via ATP/ADP translocase disappear in spite of the presence of CKmi-mi in the intermembrane space and intactness of the outer mitochondrial membrane. Therefore, this coupling cannot be explained by the "compartmented coupling" mechanism or "dynamic adenine nucleotide compartmentation" in the intermembrane space due to diffusion limitation for adenine nucleotides through the outer mitochondrial membrane, as has been supposed by several authors (F.N. Gellerich et al. (1987) Biochim. Biophys. Acta 890, 117-126; S.P.J. Brooks and C.H. Suelter (1987) Arch. Biochem. Biophys. 253, 122-132). The data obtained show that the displacement of the enzyme from the membrane results in significantly increased sensitivity of the coupled processes of aerobic phosphocreatine synthesis to inhibition by the product, phosphocreatine. Thus, all results show that under physiological osmotic and ionic conditions CKmi-mi remains firmly attached to the inner mitochondrial membrane and effectively coupled with ATP/ADP translocase due to intimate dynamic interaction between those proteins. PMID- 2912375 TI - Characteristics of an adenosine A1 binding site in human placental membranes. AB - Binding sites were solubilized from human placental membrane using 1.5% sodium cholate and were assayed using polyethylene glycol precipitation. These soluble binding sites had properties of an adenosine A1 binding site. 2 [3H]Chloroadenosine and N-[3H]-ethylcarboxamidoadenosine (NECA) binding were time dependent and reversible. Scatchard plots indicate two classes of binding sites with Kd values of 6 and 357 nM for 2-chloro[8-3H]adenosine and 0.1 and 26 nM with [3H]NECA. The specificity of [3H]NECA binding was assessed by the ability of adenosine analogs to complete for binding sites. Using this approach the estimated IC50 values were 60 nM for (R-PIA), 160 nM for S-PIA, 80 nM for NECA, and 20 nM for 2-chloroadenosine. Binding of [3H]NECA to the soluble sites is inhibited to 48% of the control value by 100 microM guanylyl-5'-imidodiphosphate (Gpp(NH)p). The IC50 value for NECA binding to the soluble binding site was increased from 80 nM to 1500 by Gpp(NH)p. There was a shift of binding affinity from a mixture of high and low affinity to only low affinity with 100 microM Gpp(NH)p. Despite these alterations a NECA prelabeled molecular species of 150 kDa did not decrease in molecular weight upon the addition of 100 microM Gpp(NH)p during high-performance liquid chromatography on a Superose 12 column. Other evidence to support the concept of preferential solubilization and assay of a small population of A1 binding sites was obtained. Following solubilization adenosine A2-like binding sites could be detected only in reconstituted vesicles. The existence of small amounts of A1 binding sites in intact human placental membranes was directly demonstrated using the A1 agonist ligand N6 [3H]cyclohexyladenosine and the A1 antagonist ligand 8-[3H]cyclopentyl-1,3 dipropylxanthine. JAR choriocarcinoma cells have "A2-like" membrane binding sites. In contrast to placental membranes, only A2-like binding sites could be solubilized from JAR choriocarcinoma cells. These observations indicate that human placental membranes contain adenosine A1 binding sites in addition to A2 like binding sites. These sites are guanine nucleotide sensitive, but do not shift to a lower molecular weight form upon assumption of a low affinity state. PMID- 2912376 TI - Fish muscle cytoskeletal network: its spatial organization and its degradation by an endogenous serine proteinase. AB - The extraction of white croaker skeletal myofibrils with KI rendered a residue in which a network of longitudinal and transverse filaments could be observed by scanning electron microscopy. A trypsin-like serine proteinase isolated from the same muscle was able to produce a complete and rapid disruption of the network, while major myofibrillar proteins were only slightly modified. This fact suggests that the disassembly of the cytoskeletal network may be an early event in the proteolysis of myofibrils. Desmin was not attacked by the proteinase under the assayed conditions, which indicates that some other unidentified component of the network would be the primary target of the action of the enzyme on myofibrils. PMID- 2912377 TI - Evaluation of equilibrium constants from precipitin curves: interaction of alpha crystallin with an elicited monoclonal antibody. AB - A simple procedure, based on the precipitin curve and the antibody:antigen ratios of the precipitates, is described for evaluation of the intrinsic association constant (k) governing the interaction between a multivalent antigen and a bivalent antibody. Its application is illustrated with a study of the interaction between alpha-crystallin and an elicited monoclonal antibody, which is shown to exhibit essentially identical affinities (k = 9 X 10(4) M-1) for the alpha m and alpha c forms of the antigen. PMID- 2912378 TI - Binding of ions and hydrophobic probes to alpha-lactalbumin and kappa-casein as determined by analytical affinity chromatography. AB - The technique of analytical affinity chromatography was extended to characterize binding of ions and hydrophobic probes to proteins. Using the immobilized protein mode of chromatography, alpha-lactalbumin and kappa-casein were covalently attached to 200-nm-pore-diameter controlled-pore glass beads and accommodated for high-performance liquid chromatography. The existence of a high affinity binding site (Kdiss = 0.16 microM) (site I) for calcium ion in alpha-lactalbumin was confirmed by chromatography of [45Ca2+]. In addition, chromatography of the hydrophobic probes, 1-(phenylamino)-8-naphthalene-sulfonate (ANS)2 and 4,4'-bis[1 (phenylamino)-8-naphthalenesulfonate (bis-ANS) indicated that Ca2+ bound to a second site (presumably the zinc site or site II) with weaker affinity. Dissociation constants obtained for apo-alpha-lactalbumin were about 80 microM for ANS and 4.7 microM for bis-ANS in the absence of sodium ion. Addition of Ca2+ initially caused a reduction in surface hydrophobicity (lowered affinity for the probe dyes) followed by an increase at higher Ca2+ concentrations (greater than 0.5 mM), suggesting that occupancy of site II restores an apo-like conformation to the protein. Moreover, the effect of Zn2+ was similar to that observed in the higher Ca2+ concentration range, whereas Na+ apparently bound to site I. A calcium binding site of moderate affinity also exists in kappa-casein (Kdiss = 15.6 microM). A cluster of negative charges, probably including the orthophosphate group, most likely comprise this binding site. By preventing self association, analytical affinity chromatography permits microscale characterization of ligand equilibria in proteins that are unaffected by protein protein interactions. PMID- 2912379 TI - Deamidation of calmodulin at neutral and alkaline pH: quantitative relationships between ammonia loss and the susceptibility of calmodulin to modification by protein carboxyl methyltransferase. AB - Measurements of ammonia release provide the first direct evidence that calmodulin becomes extensively deamidated during incubations at 37 degrees C, pH 7.4 or pH 11. A stoichiometry of 0.5 mol of NH3 released/mol of calmodulin is observed after 2 h at pH 11 or after 8-9 days at pH 7.4. These treatments also increase the ability of calmodulin to serve as a substrate for the isoaspartate-specific protein carboxyl methyltransferase from bovine brain. The stoichiometries of methylation are highly correlated with the stoichiometries of ammonia release. Deamidation and increased methyl-accepting capacity also occur in parallel for seven other proteins (aldolase, bovine serum albumin, cytochrome c, lysozyme, ovalbumin, ribonuclease A, and triosephosphate isomerase) upon incubation at pH 11. However, in comparison to calmodulin, these other proteins show very little deamidation and increased methylation capacity following incubation at pH 7.4. Deamidation of calmodulin at pH 7.4 is unaffected by the addition of 10(-7) M Ca2+; however, at 4 X 10(-6) M Ca2+, the rate of deamidation is inhibited by approximately 70%. The Ca2+-protection effect is consistent with the suggestion (B. A. Johnson, N. E. Freitag, and D. W. Aswad, (1985) J. Biol. Chem. 260, 10913 10916) that deamidation occurs preferentially at Asn-60 and/or Asn-97, each of which resides in a distinct Ca2+-binding domain. PMID- 2912380 TI - Asparagine catabolism in rat liver mitochondria. AB - A large portion of mitochondrial asparagine (Asn) is degraded by asparagine amino transferase to produce alpha-ketosuccinamate (alpha KSA), which is then hydrolized by omega-amidase to produce oxaloacetate (OAA) and ammonia. This is in contrast to the catabolism in the cytosol, where the main catabolic route for Asn occurs initially via asparaginase-catalyzed hydrolysis to form aspartate and ammonia. Mitochondrial production of OAA from Asn was followed by monitoring the decrease in the rate of succinate oxidation (which is inhibited by OAA) in both coupled and uncoupled mitochondria. Rapid OAA production was found to be dependent on the presence of both Asn and glyoxylate, and was eliminated by the aminotransferase inhibitor, aminooxyacetate (AOX). HPLC separation and quantitation of alpha-keto acids and amino acids allowed direct observation of the proposed mitochondrial pathway. Studies using L-[U-14C]Asn in mitochondria yielded labeled carbon in alpha KSA, OAA, and CO2 when either an alpha-keto acid or glyoxylate was provided. The extent of the labeled carbon in these products was greatly influenced by factors that affected the citric acid cycle and oxidative phosphorylation. Carbon dioxide production from Asn alone, even in the presence of AOX, suggested the existence of at least one additional Asn catabolic pathway in the rat liver mitochondria which does not involve alpha KSA as an intermediate. PMID- 2912381 TI - Ethanol causes decreased partitioning into biological membranes without changes in lipid order. AB - One of the adaptive responses of cell membranes to chronic ethanol consumption is the acquisition of a resistance to fluidization or disordering of the lipids by ethanol in vitro and a reduced partitioning of ethanol into the membrane (membrane tolerance). The degree to which the effects on partitioning and lipid disordering share common features has not previously been explored and in addition the relevance of the value of lipid order in the absence of added ethanol (baseline lipid order) to membrane tolerance has not been established. The location in the bilayer and the nature of the modification underlying these effects is also unknown. The effect of chronic ethanol treatment was examined using 5-doxyl decane as a model hydrophobic compound. Its partitioning into the membranes was determined by utilizing its ability to quench fluorophores (1,6 diphenyl-2,3,5-hexatriene and 3- and 12-anthroyl stearates) by collisional quenching. The partition coefficient of 5-doxyl decane into the bilayer central region was reduced as a result of the chronic ethanol treatment. The effect could also be demonstrated in vesicles of phospholipids and was lost 4 days after withdrawal of the ethanol from the diet. These results closely parallel those relating to resistance to lipid disordering and suggest that both techniques detect a common modification. Lipid order was assessed using fluorescence anisotropy measurements of a range of fluorophores, including those used to determine the partitioning properties of the membrane. No effect of chronic ethanol treatment on lipid order was found, either in the intact membranes or in vesicles of extracted phospholipids. This suggests that changes in baseline order are not critical features of membrane tolerance in liver microsomes. In addition it appears that the altered partitioning of the 5-doxyl decane into the central region of the membrane is not related to lipid order changes in this region. The reduced partitioning of 5-doxyl decane may be a reflection of a redistribution in the lipid bilayer, perhaps due to modifications in other locations in the membrane, such as the lipid head group region. PMID- 2912382 TI - Purification and characterization of human lysosomal membrane glycoproteins. AB - Two human cell lysosomal membrane glycoproteins of approximately 120 kDa, hLAMP-1 and hLAMP-2, were identified by use of monoclonal antibodies prepared against U937 myelomonocytic leukemia cells or blood mononuclear cells. The two glycoproteins were purified by antibody affinity chromatography and each was found to be a major constituent of human spleen cells, representing approximately 0.05% of the total detergent-extractable protein. Both molecules were highly glycosylated, being synthesized as polypeptides of 40 to 45 kDa and cotranslationally modified by the addition of Asn-linked oligosaccharides. NH2 terminal sequence analysis indicated that each was approximately 50% identical to the corresponding mLAMP-1 or mLAMP-2 of mouse cells. Electron microscopic studies of human blood monocytes, HL-60, and U937 cells demonstrated that the principal location of these glycoproteins was intracellular, in vacuoles and lysosomal structures but not in the peroxidase-positive granules of monocytes. Transport of the proteins between organelles was evidenced by their marked accumulation in the membranes of phagolysosomes. A fraction of each glycoprotein was also detected on the plasma membrane of U937 and HL-60 cells but not on a variety of other tissue culture cells. This cell-surface expression may be differentiation related, since the proteins were not detected in the plasma membrane of normal blood monocytes and their expression on U937 and HL-60 cells was reduced when the cells were treated with differentiating agents. Cell-surface expression of both glycoproteins was markedly increased in blood monocytes but not in U937 cells after exposure to the lysosomotropic reagent methylamine HCl, indicating differences in LAMP-associated membrane flow in these cell types. PMID- 2912383 TI - Adriamycin-dependent release of iron from microsomal membranes. AB - Microsomes incubated with NADPH and the cardiotoxic anticancer drug adriamycin reductively release their bound nonheme iron, which is accounted for by ferritin and an as yet uncharacterized nonferritin pool. The reaction is mediated by one electron reduction of adriamycin to semiquinone radical and subsequent reoxidation of this radical at the expense of membrane iron to regenerate adriamycin and promote Fe2+ release. The semiquinone radical of adriamycin can also reoxidize at the expense of molecular oxygen to form superoxide. However, superoxide dismutase does not inhibit Fe2+ release, indicating either that superoxide is not involved in iron reduction or that superoxide reacts at sites which are sterically inaccessible to the enzyme. It is proposed that the reductive mobilization of membrane-bound iron may mediate the therapeutic or toxic effects of adriamycin, irrespective of the superoxide dismutase content of the target cells. PMID- 2912384 TI - Inhibition of Na+-dependent phosphate transport by group-specific covalent reagents in rat kidney brush border membrane vesicles. Evidence for the involvement of tyrosine and sulfhydryl groups on the interior of the membrane. AB - The effects of tyrosine- and sulfhydryl-specific reagents on the Na+-dependent transport of phosphate in brush border membrane vesicles prepared from rat renal cortex were investigated. This study is the first to show that the tyrosine specific reagents 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole and tetranitromethane inactivate the transporter in a concentration- and time-dependent fashion while the membrane impermeant tyrosine reagent, N-acetylimidazole, has no effect on phosphate uptake. The membrane permeant sulfhydryl reagent N-ethylmaleimide also caused a time- and concentration-dependent inactivation of this transport process but the membrane impermeant reagents 7-chloro-4-sulfobenzo-2-oxa-1,3-diazole and eosin-5-maleimide had little effect on phosphate uptake. The inhibitory effects of both tyrosine- and sulfhydryl-specific reagents were additive, but no protection from inactivation by tyrosine-specific reagents could be achieved by preincubation of the vesicles with the substrates of the transporter or with competitive inhibitors of the transport process. These results suggest that the amino acids modified by these agents are located either within the membrane or on the cytosolic surface of the transporter. These residues may not participate in substrate binding, but may be important for the conformational change of the transporter necessary for the translocation of phosphate across these membranes. This study also shows that Na+-dependent phosphate transport can be inactivated by other reagents which covalently modify histidine, carboxyl, and amino groups on proteins. PMID- 2912385 TI - Adenosine triphosphate hydrolysis by purified rubisco activase. AB - Activation of ribulose bisphosphate carboxylase/oxygenase (rubisco) in vivo is mediated by a specific protein, rubisco activase. In vitro, activation of rubisco by rubisco activase is dependent on ATP and is inhibited by ADP. Purified rubisco activase hydrolyzed ATP with a specific activity of 1.5 mumol min-1 mg-1 protein, releasing approximately stoichiometric amounts of ADP and Pi. Hydrolysis was highly specific for ATP-Mg and had a broad pH optimum, with maximum activity at pH 8.0-8.5. ATPase activity was inhibited by ADP but not by molybdate, vanadate, azide, nitrate, or fluoride. Addition of rubisco in either the inactive or activated form had no significant effect on ATPase activity. Incubation of rubisco activase in the absence of ATP resulted in loss of both ATPase and rubisco activation activities. Both activities were also heat labile, with 50% loss in activity after 5 min at 38 degrees C and complete inhibition following treatment at 43 degrees C. Both activities showed a sigmoidal response to ATP concentration, with half-maximal activity at 0.053 mM ATP. Rubisco activation activity was dependent on the concentrations of both ATP and ADP. The results suggest that ATPase activity is an intrinsic property of rubisco activase. PMID- 2912386 TI - [Future prediction of cancer deaths in Japan]. AB - The number of cancer deaths and age-adjusted cancer death rates up to 2000 in Japan were predicted based on cancer death rates in 1972-1986. A simple linear regression model (y = a + bt, where t is calendar year and y is cancer death rate per 100,000 population) was fitted to the sex-age specific cancer mortality rates from 1972 to 1986 and cancer death rates in 1990, 1995 and 2000 were predicted by extrapolation method. The number of future cancer deaths was estimated after taking into account future population in Japan. The age-adjusted cancer rates up to 2000 were also estimated. The present study revealed that the numbers of deaths from stomach cancer (both sexes), uterine cancer and esophageal cancer (females) would keep declining, while all other cancers would increase in the future. The total number of cancer deaths in 2000 was estimated to be about 310,000 which is 1.62 times that of the total cancer deaths in 1986 (191,654). It was estimated that in 2000, lung cancer would rank top accounting for 22.2% of all cancer deaths, followed by cancers of the large intestine, liver, stomach, pancreas, biliary tract, leukemic, lymphoma and breast. PMID- 2912387 TI - [Technics in molecular biology in cancer research. DNA blot . hybridization]. PMID- 2912388 TI - [The combined effect of cisplatin and aclarubicin on human lymphocytes in vitro]. AB - The combined effect of cisplatin (CDDP) and aclarubicin (ACR) which was reported to inhibit the repair of the sublethal and the potentially lethal X-ray damages, was studied with human lymphocytes. The cell kinetics during administration of CDDP or ACR were analysed by flow cytometry. CDDP at the concentration of 0.5 microgram/ml had no effect on the cell progression. ACR blocked the cell progression at G1 period at the concentrations of 100 and 200 ng/ml, but the number of dead cells was not increased. When these two agents were combined, the number of dead cells increased more than 10 times compared to that of ACR alone. In conclusion, it was found that the combination of CDDP with ACR had a synergistic effect. PMID- 2912389 TI - [Chemo-sensitivity of a human salivary adenocarcinoma cell line to several anti cancer drugs and enhancement of the antitumor effects by combination with filipin or verapamil]. AB - A human salivary adenocarcinoma cell line, HSGc, was tested for the chemosensitivity and compared with a human squamous cell carcinoma cell line, KB. From IC50 values of anti-cancer drugs on the cells, it was found that HSGc was sensitive to CDDP, 5-FU and DTIC but resistant to ADM, MTX, VCR, PEP and MMC as compared to KB. The chemosensitivity of HSGc was in agreement with previously reported clinical data on the therapeutic results of salivary gland tumors. This suggests that HSGc may be an useful model for understanding the biological response of salivary adenocarcinoma cells to anti-cancer drugs. We further examined the combined effects of filipin and verapamil with these anti-cancer drugs. Filipin was found to enhance cell-killing effect of 5-FU and PEP on HSGc, while the combination of filipin with either DTIC or PEP was also effective on KB. Verapamil was effective in combination with 5-FU, VCR or PEP on HSGc and with DTIC, VCR or PEP on KB. Especially the most predominant enhancement on HSGc was observed in combination of filipin or verapamil with PEP. These findings suggest that even low-sensitive drug, PEP, is also useful when combined with either filipin or verapamil. PMID- 2912390 TI - Technique and results with a roller pump left and right heart assist device. AB - During the last 10 years we have inserted a roller pump-driven left heart assist device in 72 patients and a right heart assist device in 7 patients for profound heart failure after a variety of cardiac surgical procedures. In addition a percutaneous left heart assist device (transseptal insertion of left atrial cannula via a femoral vein) was employed in 5 patients with profound cardiogenic shock after acute myocardial infarction. Thirty patients (41.7%) were weaned from the left heart assist device and 21 (29.2%) were discharged from the hospital. Two patients (40.0%) were weaned from the right heart assist device, but both later died during the postoperative period. Of the 5 patients in whom a percutaneous left heart assist device was inserted, 4 underwent successful emergency percutaneous transluminal coronary angioplasty, but all 5 patients died. Causes of death included severe coagulopathy, irreversible extensive myocardial infarction and cardiac failure, refractory arrhythmias, severe "shock" lung, and multisystem failure. In summary, satisfactory results can be achieved with a roller pump-driven left and right heart assist device for severe postoperative heart failure. Further experience should be obtained with the percutaneous technique to assess its efficacy in treating patients with acute myocardial infarction and cardiogenic shock. PMID- 2912391 TI - Use of the Pierce-Donachy ventricular assist device in patients with cardiogenic shock after cardiac operations. AB - In spite of recent improvements in cardiac surgery, a small percentage of patients have severe postcardiotomy ventricular failure refractory to drugs and the intraaortic balloon. In our experience, the Pierce-Donachy external pneumatic ventricular assist device has proved to be one of the most effective devices for these patients. Since 1981, 30 patients aged 15 to 71 years (mean age, 52 years) with profound cardiogenic shock refractory to conventional therapy after cardiotomy were supported with the Pierce-Donachy ventricular assist device. Fourteen required left ventricular support, 7 needed right ventricular support with an intraaortic balloon, and 9 had biventricular assistance. Duration of support ranged from three hours to 22 days (mean length, 3.6 days). Seven of the first 11 patients seen died in the operating room of bleeding, biventricular failure, or both. However, 16 patients (53%) had improved cardiac function, 15 (50%) were weaned, and 11 (37%) were discharged. Of the last 19 patients in the series, 47% survived. Factors affecting survival were myocardial infarction (75%) and renal failure (90%). Common complications were bleeding (73%) and biventricular failure (83%). PMID- 2912392 TI - Current status of permanent total artificial hearts. AB - Pneumatic total artificial heats, although demonstrating utility as temporary mechanical circulatory support devices, have not demonstrated a great deal of promise as permanent cardiac replacements. The increasing number of patients who would be candidates for total heart replacement suggests a large role for a permanent implantable total artificial heart. To that end, the Pennsylvania State University is developing an electric motor-driven total artificial heart; the results with implants in calves are encouraging. In this device, a roller-screw mechanism is used to translate the rotation of a brushless direct-current motor into rectilinear motion of a pusher-plate assembly, which in turn empties the blood sacs. The total artificial heart of the future will function under automatic control without percutaneous leads, and this should provide the patient with a nearly normal life-style. Although further experimental efforts are necessary to prepare the device for clinical trials, the technology to provide a safe and reliable electric blood-pump system is at hand. PMID- 2912393 TI - The asymptomatic child a long time after the Mustard operation for transposition of the great arteries. AB - We studied 36 asymptomatic children 7.7 +/- 2.5 years after a Mustard operation. Fifteen children had sinus rhythm on all electrocardiograms made during follow up. Only 2 had normal 24-hour Holter recordings throughout follow-up, 6 had periods of supraventricular tachycardia, and 3 had periods of atrial flutter. The electrophysiological evaluation of sinus node function was normal in 5 of the 31 children who were studied. The behavior of the atrial myocardium was electrophysiologically abnormal in most of the children. Atrioventricular node function, on the contrary, was normal in nearly all of the children. Eleven children had normal hemodynamics. Four had severe or complete obstruction of the superior vena cava, 1 had a severe pulmonary venous obstruction, 3 had a severe left ventricular outflow tract obstruction, and 2 had a large left-to-right shunt. Only 3 children had normal hemodynamic and electrophysiological studies. We conclude that the absence of symptoms and a normal routine examination of children a long time after a Mustard operation does not exclude hemodynamic and electrophysiological abnormalities, which can sometimes be severe. In view of these disappointing results, we decided to replace the Mustard operation with the arterial switch operation in children with transposition of the great arteries. PMID- 2912394 TI - Use of a total wash-out method in an open heart operation. AB - Pathological cold agglutinins may induce hemolysis in patients who need hypothermic cardiopulmonary bypass and blood transfusion. A simple technique, termed the total wash-out method, was used in a patient with high thermal amplitude, moderate-titer cold agglutinin before hypothermic cardiopulmonary bypass. The patient's cold agglutinin titer decreased abruptly after operation. None of the preoperative hemolysis phenomena were found during her 6 months of follow-up. PMID- 2912395 TI - Circulatory Support 1988. Topical meeting of the Society of Thoracic Surgeons. February 6-7, 1988, St. Louis, MO. PMID- 2912396 TI - Circulatory Support 1988. Patient selection. PMID- 2912398 TI - Circulatory Support 1988. Intraoperative management. PMID- 2912399 TI - Circulatory Support 1988. Bleeding and anticoagulation. PMID- 2912400 TI - Circulatory Support 1988. Other postoperative complications. PMID- 2912401 TI - Infectious disease among Ethiopian immigrants in Israel. AB - From 1980 to 1985, 14,465 refugees arrived in Israel from Ethiopia. Typhoid fever, tuberculosis, or malaria was present in 1.8% to 9% of immigrants; as many as 93% were infested with intestinal parasites. Extreme malnutrition was common, and serologic evidence of syphilis and hepatitis B was frequently encountered. A program for diagnosis, therapy, and immunoprophylaxis following the massive influx of African refugees is described. PMID- 2912402 TI - Estrogen replacement therapy. A survey of women's knowledge and attitudes. AB - Because the significant health risks related to postmenopausal osteoporosis can be reduced by estrogen replacement therapy (ERT), this study assessed women's attitudes toward ERT to assess factors that might increase its use. Results showed that women taking ERT were more likely to know that decreased estrogen levels lead to osteoporosis, to perceive that menopause is a medical condition, to believe that natural approaches to menopause are less preferable, to be seeing a gynecologist for care, and to believe that women should take ERT for hot flashes. The study suggests that a systematic educational approach could influence women's willingness to take ERT, especially if the recommended therapy does not cause withdrawal bleeding. PMID- 2912403 TI - Results of a television-advertised public screening program for colorectal cancer. AB - We report the results of a free, television-advertised mass screening program for colorectal cancer using stool guaiac kits. A total of 57,000 test kits were picked up and 29,619 (53%) were returned; 3.9% (1165) of the tests were positive. Ninety-three percent of persons with a positive screen sought medical evaluation after screening. Detailed follow-up was available on 744 persons. Fifty-eight persons had large-bowel carcinomas diagnosed, 80% of which were localized. One hundred sixty persons had adenomatous polyps removed. Forty percent of cancers and 58% of polyps were detected in persons with only one or two positive test slides out of a total of six. In 33% of persons with a positive screen, the diagnostic workup consisted of a repeated stool guaiac test and/or sigmoidoscopy only. A major drawback to improving the results of mass screening programs for colorectal cancer is the limited gastrointestinal workup conducted by physicians in many persons with a positive fecal occult blood test. PMID- 2912404 TI - Diagnostic studies for systemic necrotizing vasculitis. Sensitivity, specificity, and predictive value in patients with multisystem disease. AB - Forty patients with multisystem disease and suspected systemic necrotizing vasculitis were evaluated with a protocol designed to confirm the diagnosis with sequential testing. All patients underwent initial laboratory testing. Subsequent studies were individualized to the patient starting with "safe" tests (skin, muscle, rectal biopsies) and progressing to "invasive" tests (arteriography, kidney and lung biopsies). No single laboratory study was found to have adequate predictive value. Skin biopsy, rectal biopsy, and arteriography were insensitive, nonspecific, or had poor predictive values. Muscle biopsy was the most valuable safe procedure (sensitivity, 50%; specificity, 100%; predictive value, 100%; predictive value of negative biopsy, 76%; efficiency, 64%). A diagnostic approach to the patient with possible systemic necrotizing vasculitis is described. PMID- 2912405 TI - Community- and hospital-acquired pneumonia associated with Chlamydia TWAR infection demonstrated serologically. AB - Serum specimens from 198 patients with pneumonia hospitalized in Seattle between October 1980 and April 1981 were retrospectively tested for antibody against a recently described Chlamydia organism called TWAR. They had been previously tested for antibody for some viruses and Mycoplasma. Twenty (10%) had serologic evidence of recent TWAR infection. The hospital records of the patients with acute TWAR antibody and an equal number of matched controls were examined for clinical characteristics, laboratory tests, treatment, and course during the hospital stay. It was not possible clinically or roentgenographically to distinguish pneumonia associated with TWAR antibody from pneumonia in the controls. Nine of 20 patients with TWAR antibody acquired pneumonia during their hospital stay. The mode of transmission in the hospital was not determined. All the patients with hospital-acquired pneumonia had been intubated, and all had had some surgical procedure. Ten of 20 control patients had onset of their pneumonia in the hospital. Fifteen (11%) of 142 of the patients with pneumonia had evidence of influenza A virus infection. The clinical characteristics of their pneumonias were similar to those of the patients with acute TWAR antibody. PMID- 2912406 TI - Reported illness and compliance in US travelers attending an immunization facility. AB - Two hundred fourteen international travelers were retrospectively interviewed by telephone. The incidence of diarrhea was found to be highest in East Africa (44%) and Southeast Asia (42%). Other reported illnesses were rare, the highest incidence occurring in China with four upper respiratory tract infections reported among ten travelers. Antimalarial compliance was assessed and found to be age-related, with noncompliance reported in 41% of patients younger than 40 years and in only 19% of patients older than 40 years. Eight of 35 women who were receiving chloroquine phosphate reported menstrual irregularities. Further investigation of this possible association is underway. We continue to stress compliance with antimalarial medication. PMID- 2912407 TI - Constrictive pericarditis presenting as pleural effusion of unknown origin. AB - Despite the known association of pleural effusion with constrictive pericarditis, the presentation of constrictive pericarditis as pleural effusion of unknown origin has, to our knowledge, never been described. After evaluating such a case, we retrospectively analyzed all cases of established constrictive pericarditis seen in this institution in the last six years. The clinical and laboratory features of this cohort of 30 patients are similar to those of other reported series. Pleural effusion was present in 18 (60%) of 30 cases. In six (12%) of the 18 cases, pleural effusion was a major component of the clinical presentation, and in three (10%) of these six cases, the persistence of pleural effusion of unknown origin was the indication for referral to this institution. Analysis of pleural fluid in four cases revealed three exudates and one transudate. We believe this is the first report of unexplained pleural effusion as the presenting manifestation of constrictive pericarditis, and this diagnosis should be added to the list of causes of unexplained pleural effusion. PMID- 2912408 TI - Protein intake and kidney function in humans: its effect on 'normal aging'. AB - The effect of dietary protein on kidney function expressed by creatinine clearance was studied in healthy subjects following a "normal" unrestricted protein diet and compared with a group of vegetarians maintained on a long-term low-protein diet. Both groups had similar kidney function and displayed the same rate of progressive deterioration in renal function with age. These results suggest that, in contrast with the important therapeutic effect of low-protein intake on the progressive deterioration of kidney function in diseased kidneys, such a diet does not significantly affect kidney function with "normal aging" in healthy subjects. PMID- 2912409 TI - Improved safety of glucagon testing for pheochromocytoma by prior alpha-receptor blockade. A controlled trial in a patient with a mixed ganglioneuroma/pheochromocytoma. AB - The glucagon stimulation test has been superseded in recent years by the clonidine suppression test because it can provoke dangerous increases in blood pressure in patients with pheochromocytomas. We describe the first patient in whom a pheochromocytoma was diagnosed by a glucagon test, after which the blood pressure (but not the plasma catecholamine) response to a second injection of glucagon was blocked by pretreatment with phenoxybenzamine. After the tumor (which contained both pheochromocytoma and ganglioneuroma tissue) was removed, a third glucagon test result was negative. This experience suggests that patients with normal plasma catecholamine levels who are suspected of harboring a pheochromocytoma may be accurately diagnosed, but potentially dangerous increases in blood pressure may be minimized, by performing the glucagon test after alpha adrenergic blockade. PMID- 2912410 TI - Diltiazem and sinus arrest in connection with atenolol and digoxin. PMID- 2912411 TI - Exercise in controlling serum lipid levels. PMID- 2912412 TI - Pitting edema and hypertrophic pulmonary osteoarthropathy. PMID- 2912413 TI - Disseminated gonococcal infection. PMID- 2912414 TI - Training of family members of high-risk cardiac patients in cardiopulmonary resuscitation. Skills performance and need for physician recommendations. PMID- 2912415 TI - Effects of nandrolone decanoate and antiresorptive therapy on vertebral density in osteoporotic postmenopausal women. AB - Conventional antiresorptive therapy for osteoporosis can delay bone loss, but secondary inhibition of bone formation appears to prevent an increase in bone density. Recently, anabolic steroid therapy has been shown to increase total body calcium and forearm density in osteoporotic patients, perhaps by causing an increase in bone formation. It is not known if these agents affect vertebral density. We have measured vertebral mineral density in 71 postmenopausal osteoporotic women before and after treatment with either the anabolic steroid nandrolone decanoate or antiresorptive therapy. After a mean treatment period of 14 months, there was a mean increase of 20% in vertebral mineral density in the former group, and no significant change in the latter group. The difference in the time-weighted mean rates of change between the two groups was significant. The results suggest that nandrolone decanoate therapy increases bone formation. PMID- 2912416 TI - Can family members of high-risk cardiac patients learn cardiopulmonary resuscitation? AB - The immediate delivery of bystander-administered cardiopulmonary resuscitation (CPR), coupled with the rapid delivery of advanced cardiac life support, can significantly reduce mortality from out-of-hospital cardiac arrest. Because the majority of sudden cardiac deaths occur in the victim's home with family members present, family members of cardiac patients at high risk for sudden death are the logical focus of CPR training. However, previous research has shown that only a small minority of family members of cardiac patients actually learn CPR and that health care professionals have failed to recommend CPR training in this population, in part due to concerns about their ability to learn CPR. The purpose of this study was to describe learning capabilities in this population and to identify characteristics of unsuccessful learners. To this end, we taught CPR to 83 family members of cardiac patients who were at risk for sudden cardiac death. Subjects had no CPR training within the past two years. Eighty-one percent of the subjects successfully learned CPR. Of the demographic and psychological characteristics examined, only gender, age, and depression were significant in explaining differences in CPR skills attainment ability. The elderly, the depressed, and males were more likely to be unsuccessful in demonstrating adequate CPR skills. Our results suggest that the majority of family members of cardiac patients can learn CPR successfully. Specific training strategies may need to be developed and tested to enhance CPR training in those family members of cardiac patients predicted to have difficulty learning CPR. PMID- 2912417 TI - Intensive care unit patient follow-up. Mortality, functional status, and return to work at six months. AB - Six months after hospital discharge, we followed up 1545 patients who had received care in the general medical-surgical intensive care unit (ICU) of a tertiary care hospital. Vital status could not be ascertained for 200 of these patients. Of the 1345 former ICU patients for whom a determination of vital status could be made, 1261 (94%) were alive and 84 (6%) had died. Of those known to be living, 887 (70%) responded to a questionnaire regarding employment, functional, and social status. A large proportion of survivors less than 40 years of age had returned to work. Younger patients admitted to the hospital for elective surgery reported as much compromise of physical and psychological activity as did older patients admitted for emergency reasons. Older survivors reported an increase of interaction with family members and a decrease of social interaction with those other than family. PMID- 2912418 TI - Influenza A among hospital personnel and patients. Implications for recognition, prevention, and control. AB - An outbreak of influenza A/Philippines H3N2 at a 1156-bed Veterans Administration Hospital involved 118 hospital personnel and 49 patients. Prospective surveillance methods that had been established within the hospital were not useful in identifying the number of involved individuals. Community indicators of influenza, which were reviewed retrospectively, would not have identified circulating influenza in this population. Control of the outbreak was accomplished using a creative approach that immunized over a third of the physician and nursing staff. This immunization program was successfully used in subsequent years to increase personnel compliance with the Immunization Practices Advisory Committee recommendations to annually immunize hospital personnel. PMID- 2912419 TI - A comparison between a conventional and a fiberoptic flow-directed thermal dilution pulmonary artery catheter in critically ill patients. AB - Invasive hemodynamic monitoring is frequently required in the management of patients in intensive care units. A fiberoptic flow-directed thermal dilution pulmonary artery catheter capable of continuously monitoring the mixed venous saturation, while more expensive than a conventional pulmonary artery catheter, theoretically could result in better patient care, and might be cost-effective if it resulted either in fewer blood tests being ordered or in less time in the intensive care unit. To test this hypothesis, we designed a randomized trial in our Medical Intensive Care Unit to compare a standard pulmonary artery catheter with a fiberoptic catheter. Twenty-six patients received a standard catheter and 25 patients received the fiberoptic catheter. There were no statistical differences between the groups in age, time in the intensive care unit, number of tests ordered, hours of mechanical ventilator therapy, hours of vasoactive drug therapy, or mortality rate. The only statistically significant differences between the groups were that (1) the fiberoptic catheter required a longer insertion time and (2) there were more technical problems in consistently obtaining the wedge pressure in the patients with the fiberoptic catheters. We conclude that routine substitution of a fiberoptic catheter for the standard pulmonary artery catheter is not indicated. PMID- 2912420 TI - The Apoprotein and Antibody Standardization Program. The Apoprotein and Antibody Standardization Program Planning Committee. PMID- 2912422 TI - Dietary fish oil increases conversion of very low density lipoprotein apoprotein B to low density lipoprotein. AB - Dietary fish oils, which are rich in omega-3 fatty acids, are known to produce a marked lowering of very low density lipoprotein (VLDL) triglyceride concentrations, but they have a less marked effect on low density lipoprotein (LDL) cholesterol. Our previous apolipoprotein (apo) B kinetic studies in miniature pigs demonstrated that conversion of VLDL apo B to LDL apo B accounted for 15% to 20% of total VLDL apo B catabolism. In addition, 75% to 80% of LDL apo B was derived independent of plasma VLDL or intermediate density lipoprotein (IDL) apo B catabolism. The present studies were carried out to determine if fish oil diets influenced: 1) the conversion of VLDL to LDL, and 2) the pathways of LDL apo B synthesis. Autologous 125I-VLDL and 131I-LDL were injected into four pigs after both a corn-oil (30 g/day for 18 days) and a Maxepa (30 g/day for 18 days) dietary period. Analysis of apo B specific activity curves demonstrated that fish oil reduced the VLDL pool size by 38% (p less than 0.05) due to an increase in fractional catabolic rate (0.83 +/- 0.13 vs. 0.48 +/- 0.03 hr-1), as the synthesis rate was unaffected. However, the proportion of VLDL apo B converted to LDL increased significantly (56 +/- 7% vs. 17 +/- 3%, p less than 0.01) whereas the proportion cleared directly decreased (46 +/- 5% vs. 83 +/- 3%, p less than 0.005). Fish oil reduced total LDL apo B synthesis (0.6 +/- 0.1 vs. 1.1 +/- 0.2 mg/hr/kg, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2912421 TI - Apolipoprotein E2(Arg158----Cys) frequency in a hyperlipidemic French-Canadian population of apolipoprotein E2/2 subjects. Determination by synthetic oligonucleotide probes. AB - An underlying cause of type III hyperlipoproteinemia is the presence of variant forms of apolipoprotein (apo) E that are defective in binding to apo B,E low density lipoprotein receptors. This disorder is associated almost exclusively with the apo E2/2 phenotype. However, structural and functional heterogeneity have been demonstrated within this phenotype. The apo E2(Arg158----Cys) variant, displaying 1% of normal apo E3 binding activity, is the most defective known form. In this study, we describe a method in which a pair of 19-mer synthetic oligonucleotide probes were used to distinguish between DNA coding for arginine or cysteine at position 158 in apo E. The specificity of the probes was demonstrated by using DNA from subjects whose apo E protein sequence or phenotype was known. The probes were used to screen a French-Canadian population of 34 apo E2/2 subjects to determine the frequency of the apo E2(Arg158----Cys) variant. All 34 subjects, most of whom displayed clinical or biochemical features of type III hyperlipoproteinemia, were found to be homozygous for apo E2(Arg158----Cys), strongly suggesting that this variant is the most common form of apo E2 within this ethnic and clinical population. In addition, the utility of this approach in detecting new apo E mutants was demonstrated when DNA from one of the apo E3/3 control subjects, whose family has a history of hyperlipidemia and coronary artery disease, reacted with both probes. This result suggests that this subject is heterozygous for normal apo E3 and a new apo E3 variant that is likely to be functionally equivalent to apo E2(Arg158----Cys). PMID- 2912423 TI - Intralipid infusion abolishes ability of human serum to cholesterol-load cultured macrophages. AB - Intralipid is widely used for intravenous alimentation and contains triglyceride emulsion particles and phospholipid liposomes. After infusion, triglyceride emulsion particles resemble chylomicron remnants and thus may be atherogenic. On the other hand, intravenous infusion of phospholipid liposomes produces regression of experimental atherosclerosis and abolishes the ability of hypercholesterolemic rabbit plasma to cholesterol-load cultured macrophage foam cells. To determine the net effect of intralipid infusion on cellular cholesterol balance, J-774 macrophages were incubated for 18 hours with human serum obtained before, during, and after a 6-hour infusion of 10% Intralipid. Compared to serum free medium, pre-infusion serum increased cellular unesterified cholesterol by 76% and cholesteryl ester by 78%. In contrast, serum obtained after the 6-hour infusion reduced cellular unesterified cholesterol by 23% and cholesteryl ester by 15%. Serum obtained 18 hours after the end of the infusion still showed impaired cholesterol-loading ability. Mouse peritoneal macrophages incubated with these serum samples behaved similarly. Compared to pre-infusion serum, postinfusion serum inhibited cellular uptake of 125I-low density lipoprotein and 125I-very low density lipoprotein by 50% and 80%, respectively, and also enhanced the efflux of cellular cholesterol by 46%. We conclude that the ability of human serum to cause cholesterol accumulation in cultured macrophages is abolished by an infusion of Intralipid. This effect is mediated by a reduction in cholesterol uptake by the cells and by an increase in cell cholesterol efflux. If similar events occur in the arterial wall, Intralipid infusion might inhibit foam cell formation in vivo. PMID- 2912425 TI - International Symposium on Familial Hypercholesterolemia. Oslo, Norway, August 28 29, 1987. Proceedings. PMID- 2912424 TI - Structure of apolipoprotein B-100 of human low density lipoproteins. AB - We have analyzed low density lipoproteins (LDL) apolipoprotein (apop) B structure by direct sequence analysis of LDL apo B-100 tryptic peptides. Native LDL were digested with trypsin, and the products were fractionated on a Sephadex G-50 column. The partially digested apo B-100 still associated with lipids was recovered in the void volume (designated trypsin-nonreleasable, TN, peptides). The released peptides (designated trypsin-releasable, TR, peptides) in subsequent peaks were repurified on two successive high-performance liquid chromatography (HPLC) columns. The TN peak was delipidated and redigested with trypsin, and the resulting peptides were purified on two successive HPLC columns. Using this approach, we sequenced over 88% of LDL apo B-100, extending and refining our previous study (Nature 1986;323:738-742) which covered 52% of the protein. TN peptides made up 31%, and the TR peptides, 34% of the apo B-100 sequence; 23.7% were found under both TN and TR categories. Based on its differential trypsin releasability, apo B-100 can be divided into five domains: 1) residues 1----1000, largely TR; 2) residues 1001----1700, alternating TR and TN; 3) residues 1701--- 3070, largely TN; 4) residues 3071----4100, mainly TR and mixed; and 5) residues 4101----4536, almost exclusively TN. Domain 1 contained 14 of the 25 Cys residues in apo B. Domain 4 encompassed seven N-glycosylation sites, and contained the putative receptor binding domains. All 19 potential N-glycosylation sites were directly sequenced: 16 were found to be glycosylated and three were not. Three pairs of disulfide bridges were also mapped. Finally, a combination of cDNA sequencing, direct mRNA sequencing, and comparison of published apo B-100 sequences allowed us to identify specific amino acid residues within apo B-100 that seem to represent bona fide allelic variations. Our study provides information on LDL apo B-100 structure that will be important to our understanding of its conformation and metabolism. PMID- 2912426 TI - Optimal nutritional therapy in treatment of hyperlipoproteinemias. AB - Nutritional therapies should play a key role in the treatment of elevated blood lipids. However, lack of adherence to these therapies has limited their widespread application. The contemporary challenge is to design care programs that maximize the potential for compliance. In this article, compliance is defined, and the factors that support patient adherence are described. The conditions necessary to produce behavioral change are outlined and related to program components. Finally, the selection of dietary goals and therapeutic eating patterns that provide the basis for the definition of these behavioral changes necessary for compliance are presented. PMID- 2912428 TI - Treatment of familial hypercholesterolemia with drugs in children. AB - We assessed plasma lipid levels in children and adolescents who were on various drug regimens and who were attending a specialized lipid treatment center. All subjects had familial hypercholesterolemia (FH), and the study group included 30 subjects with heterozygous (He) and three with homozygous (Ho) FH. In the 30 He FH subjects treated with 5 to 30 g/day of a bile-acid-binding resin, plasma lipid levels were still substantially above optimal (less than or equal to 50th percentile for age and sex), although statistically significant (p less than 0.001) reductions in total and low density lipoprotein (LDL) cholesterol of 15% and 21% compared with baseline were achieved. In eight subjects who received resin plus niacin, additional reductions in total and LDL cholesterol of 15% and 17%, respectively, were achieved. Even though the combination therapy produced reductions in total, LDL, and LDL/high density lipoprotein cholesterol of 29%, 37%, and 47%, respectively, compared with baseline, resulting absolute levels were still well above optimal. Six subjects with severe He FH received a 3 hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor (lovastatin, 80 mg/day or simvastatin, 40 mg/day), and substantial total and LDL cholesterol reductions on the order of 35% and 41%, respectively, were found compared with diet alone. The decreases were substantially greater than those achieved with either resin or resin plus niacin. In a number of these subjects, absolute lipid levels were approaching optimal levels. In the three Ho FH subjects, the response to HMG CoA reductase inhibitors was variable but generally poor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2912427 TI - Effects of combined therapy with lovastatin and colestipol in heterozygous familial hypercholesterolemia. Effects on kinetics of apolipoprotein B. AB - This investigation was carried out in 10 male patients with heterozygous familial hypercholesterolemia to determine the effects of combined drug therapy with lovastatin and colestipol on the kinetics of apolipoprotein B (apo B) in low density lipoproteins (LDL) and very low density lipoproteins (VLDL). Drug treatment produced reductions in plasma total cholesterol and LDL cholesterol averaging 41% and 48%, respectively. Levels of LDL apo B declined by only 34%, which resulted in a reduction in LDL cholesterol/apo B ratios. The major change in LDL apo B kinetics was a marked increase in fractional catabolic rate for LDL apo B, while production rates for LDL apo B were not changed. Combined drug therapy likewise produced a striking reduction in VLDL cholesterol. This change was associated with an increased clearance of a slowly catabolized fraction of VLDL apo B. Production rates for total VLDL apo B were unchanged. Overall, the combination of lovastatin and colestipol reduced plasma cholesterol and lipoprotein fractions to an acceptable range, and the primary mechanism appeared to be via an increase in the activity of LDL receptors and not by a reduction in production rates of lipoproteins. PMID- 2912429 TI - Plasmapheresis in familial hypercholesterolemia. AB - Twelve years' experience confirms that plasma exchange beneficially influences the course of homozygous familial hypercholesterolemia. Pilot studies with low density lipoprotein (LDL) apheresis using a dextran sulphate affinity column suggest that this procedure has advantages over plasma exchange, which it may eventually replace. Combination therapy with lovastatin and LDL apheresis is currently being assessed as a means of inducing regression of coronary lesions. Preliminary results of a pilot study in four patients with heterozygous familial hypercholesterolemia are encouraging. PMID- 2912431 TI - Lipoprotein metabolism in familial hypercholesterolemia. AB - Low density lipoprotein (LDL) receptor deficiency, which causes homozygous familial hypercholesterolemia (FH), is accompanied by a gross disturbance in the metabolism of apolipoprotein (apo) B-containing lipoproteins. Not only is plasma LDL increased, but also the less dense lipoproteins (of very low and intermediate density) accumulate to a similar extent. Only the largest triglyceride-rich subfraction of very low density lipoprotein (VLDL) is not affected. The metabolic disturbance is characterized by oversynthesis of apo B and a defect in its clearance along the length of the delipidation cascade from VLDL to LDL. This phenomenon leads to delayed transit of particles through the system, extending the residence time of the B protein in the plasma by three- to fourfold. Receptor deficiency, therefore, results in accumulation of a number of lipoprotein species that have been implicated in the pathogenesis of atherosclerosis. PMID- 2912430 TI - Evolution and progression of atherosclerotic lesions in coronary arteries of children and young adults. AB - In an autopsy study of the evolution of atherosclerotic lesions in young people, we obtained the coronary arteries and aortas of 1160 male and female subjects who died between full-term birth and age 29 years. In this article, we report the light and electron microscopic observations of the coronary arteries of 565 of these subjects in which we fixed the coronary arteries by perfusion with glutaraldehyde under pressure. From birth, the intima was always thicker in the half of the coronary artery circumference opposite the flow-divider wall of a bifurcation (eccentric thickening). In cases where we found lipid in the intima, there was always more in eccentric thickening. Isolated macrophage foam cells in the intima of infants were the earliest sign of lipid retention. These cells occurred in 45% of infants in the first 8 months of life but decreased subsequently. At puberty, more substantial accumulations of macrophage foam cells reappeared in more children. Foam cells were now accompanied by lipid droplets in existing smooth muscle cells and by thinly scattered extracellular lipid. Sixty five percent of children between ages 12 and 14 years had such lesions. An additional 8% of children had progressed beyond this early stage and had developed advanced preatheroma or atheroma stages. Such advanced lesions, located only in areas of eccentric thickening, were characterized by the addition of massive extracellular lipid that displaced normal cells and matrix and, thus, damaged and weakened the arterial wall.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2912432 TI - Identification of low density lipoprotein receptor abnormalities by assaying functional receptors on proliferating lymphocytes. AB - Lymphocyte proliferation stimulated by mitogenic lectins is dependent on exogenously supplied cholesterol when endogenous cholesterol synthesis is blocked with the specific inhibitor mevinolin. Lymphocytes from patients homozygous for familial hypercholesterolemia (FH) lack low density lipoprotein (LDL) receptors, and, therefore, these patients cannot use LDL cholesterol to support proliferation when endogenous sterol synthesis is blocked. Thus, LDL receptors are required for the uptake of exogenous lipoprotein cholesterol by proliferating lymphocytes. As a result, the number of functional receptors can be assessed when endogenous sterol synthesis is inhibited and when limiting concentrations of LDL are employed to support lymphocyte proliferation. Lymphocytes from patients heterozygous for LDL receptor abnormalities can be distinguished from normal lymphocytes since the former require twice the concentration of LDL for proliferation. By contrast, in hyperlipidemia not caused by FH, lymphocyte LDL receptor activity is normal, indicating that plasma cholesterol levels do not account for abnormalities in LDL receptor function assayed in this way. Therapy with cholesterol-lowering drugs, however, can alter lymphocyte LDL receptor activity in patients with heterozygous FH. Patients with heterozygous FH respond to therapy with mevinolin and a bile-acid-binding resin by lowering plasma cholesterol levels. In some patients, treatment with cholesterol-lowering plasma cholesterol levels. In some patients, treatment with cholesterol-lowering plasma cholesterol agents is also associated with normalization of functional lymphocyte LDL receptor activity, thereby providing direct evidence that therapy can alter LDL receptor expression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2912433 TI - Clinical features of familial hypercholesterolemia. AB - The clinical consequences of familial hypercholesterolemia (FH) result from its metabolic peculiarities that persist from very early childhood, leading to the accumulation of cholesterol in the form of xanthomas in skin and tendons and atheromatous lesions in the arterial wall, in particular, in the aorta and the stem of coronary arteries. Plasma cholesterol concentration markedly increases during the suckling period, soon attaining a level near 1000 mg/dl in homozygotes and 200 to 400 mg/dl in heterozygotes. By age 50, about 80% of FH males suffer from ischemic heart diseases, while only 20% to 30% of the females are moderately affected by coronary atherosclerosis. In addition to the low density lipoprotein (LDL) cholesterol level, higher triglyceride and lower high density lipoprotein (HDL) cholesterol levels correlate with an increased risk of ischemic heart diseases. A very important problem is that most of these patients do not feel themselves to be seriously ill until a severe myocardial infarction (often leading to sudden death) takes place during the third to fifth decades of life. Among the different types of receptor mutations, the incidence of ischemic heart diseases was much higher and more extensive among patients with the receptor negative type than among those with the receptor-defective type with a residual receptor activity. PMID- 2912434 TI - Genotypic and phenotypic variation in familial hypercholesterolemia. AB - Familial hypercholesterolemia is characterized by an increase in low density lipoprotein (LDL) cholesterol, tendon xanthomata, and premature atherosclerosis. In homozygotes, phenotypic expression of the disorder is dominated by genotypic variation at the LDL-receptor gene locus, with other influences, like gender, exerting relatively little effect. In contrast, phenotypic variation in heterozygotes is influenced not only by the nature of the underlying gene mutation but also by gender, diet, and other forms of genetic polymorphism, including the apolipoprotein E genotype. PMID- 2912435 TI - Progression of coronary atherosclerosis in patients with probable familial hypercholesterolemia. Quantitative arteriographic assessment of patients in NHLBI type II study. AB - A computer-assisted method for quantitatively assessing progression and regression of coronary atherosclerosis has been applied, in a fully blinded fashion, to a set of 116 5-year-interval coronary arteriograms obtained between 1972 and 1981 in the National Heart, Lung, and Blood Institute (NHLBI) Type II Study. Coronary changes are described in 54 of these patients who had tendinous xanthomata and hypercholesterolemia consistent with the diagnosis of familial hypercholesterolemia. Among 468 patent lesions of all degrees of severity and among 25 total occlusions identified on the initial arteriogram, 11% progressed by the 95% confidence criterion for assessing change in percent stenosis (+/- 17%), and 1% regressed by using the same criterion. Among 54 patients, 50% had progression only, 6% had regression only, and 4% had mixed progression and regression. Because half of these patients were treated with cholestyramine, these frequencies may underestimate the natural history of their disease progression. Comparable frequencies were obtained by using the 95% confidence criterion for change in stenosis resistance (Rp ratio outside range, 0.35 to 2.9). In properly obtained arteriograms, the Rp parameter is physiologically relevant and is a sensitive index of lesion change with a high signal-to-noise ratio; we advocate its use for detection of progression and regression. Morphologic features, including luminal irregularity and ulceration, increased the likelihood of progression by 1.8- to 5-fold. Surprisingly, significant arterial flexing at the site of the lesion predicted anatomic stability. A lumen narrowed by visible thrombus was 100-fold more likely to regress than were those without it. The initial severity of stenosis correlated strongly with new total occulusion and with disease progression as assessed by Rp change. Because lesion specific features are important determinants of lesion change, intervention trials that statistically account for the contributions of lesion morphology are likely to provide a more insightful assessment of the therapeutic benefit. PMID- 2912436 TI - The agony and the ecstasy. PMID- 2912437 TI - Amoxycillin with clavulanic acid. PMID- 2912438 TI - Sharing research ideas. PMID- 2912439 TI - Nurse and the law. PMID- 2912440 TI - The third age. PMID- 2912441 TI - Staurosporine, a protein kinase C inhibitor interferes with proliferation of arterial smooth muscle cells. AB - Staurosporine (10 ng/ml and more), a protein kinase C inhibitor, inhibited the serum-stimulated growth of smooth muscle cells. This inhibitory effect proved to be linked to the inhibition of transition from the G0 to the S phase of the cell cycle, as measured by 5-bromodeoxyuridine incorporation into the nuclei. As this inhibitory effect of staurosporine was restricted to the first 10 hours of the stimulation, reactions which are essential for the signal transduction may be associated with actions of protein kinase C. The possibility that staurosporine may inhibit cell growth via inhibition of this step warrants further attention. PMID- 2912442 TI - Reversibility of the thermal transitions of chloroplast thylakoid membranes. AB - Thylakoid membranes from cucumbers and peas have been examined by high sensitivity differential scanning calorimetry. Data was collected during both heating and subsequent cooling scans in order to observe reversibility. Cucumber thylakoids exhibited almost no reversibility; a very small reversible exothermic peak was observed at approximately 12 degrees C in cooling scans. However, thylakoids from peas had reversible transitions at 50 and 68 degrees C, as well as other transitions which were visible as shoulders in a second heating scan. When pea grana thylakoids were unstacked, the high temperature transitions were sharpened and their reversibility was enhanced. This is the first report of chloroplast thylakoid membranes exhibiting reversible high temperature transitions. The results indicate that considerable variation can occur in the calorimetric profiles of thylakoids from different plants. PMID- 2912443 TI - Distal His----Arg mutation in bovine myoglobin results in a ligand binding site similar to the abnormal beta site of hemoglobin Zurich (beta 63 His----Arg). AB - Carbon monoxide binding to a myoglobin mutant with distal arginine in place of histidine has been examined. The mutant is derived from a cDNA clone for Mb mRNA from fetal bovine skeletal muscle. The mutation only slightly perturbs visible/Soret spectra whereas the infrared spectrum of liganded CO is greatly modified to become nearly identical to Hb Zurich beta-subunit spectrum. The mutant IR spectra differ substantially from spectra of wild-type MbCO and normal HbCO beta-subunit. For both the Mb and the Hb the distal His----Arg mutation increases the affinity for CO and reduces the number of observed conformers. These results demonstrate that this mutation greatly reduces the differences between Mb and Hb in the structure and properties of its ligand binding sites. PMID- 2912444 TI - Intrasubstrate steric interactions in the active site control the specificity of the cAMP-dependent protein kinase. AB - The cAMP-dependent protein kinase catalytic subunit phosphorylates serine residues more efficiently than threonine residues in synthetic peptides. In marked contrast, both amino acids are phosphorylated at similar rates when contained within the appropriate intact protein substrate. The structural basis for the discriminatory behavior observed in small peptides has been investigated and found to be a result of intrapeptide steric interactions in the vicinity of the threonine alcohol moiety. Leu-Arg-Arg-Gly-Thr-Leu-Gly, which is nearly free of these interactions, is phosphorylated at a rate that is almost comparable to its serine-containing counterpart. PMID- 2912445 TI - Identification and tissue distribution of messenger RNA for the growth hormone receptor in the rabbit. AB - Rabbit liver, a rich source of specific growth hormone (GH) receptors, contains three mRNA transcripts (4.2-4.5 kb, 3.1-3.2 kb, and 1.8-2.0 kb) which hybridize strongly to oligonucleotide probes complementary to nucleotide sequences in the extracellular and cytoplasmic regions of the rabbit liver GH receptor. The approximately 4.5 kb transcript was the most abundant and showed some sex difference (male greater than female) and a significant, approximately 2 fold increase in late pregnancy - observations consistent with changes seen in the specific 125I-hGH binding capacity of rabbit liver membranes prepared from the same tissue samples. The approximately 4.5 kb mRNA species, but not the smaller transcripts, was also detected, at lower abundance, in rabbit kidney, heart and lung but not in mammary gland, which is known to lack 125I-GH binding activity. These studies have identified the nature of the mRNA transcripts coding for the GH receptor in recognized/potential GH target tissues in the rabbit. The regulation of the major GH receptor mRNA in rabbit liver appears to broadly reflect known changes in expressed receptor protein. PMID- 2912446 TI - Suppression of TNF-stimulated proliferation of diploid fibroblasts and TNF induced cytotoxicity against transformed fibroblasts by TGF-beta. AB - Human transforming growth factor-beta (TGF-beta) dose-dependently inhibited proliferation of WI-38 cells, normal human diploid fibroblasts, stimulated by tumor necrosis factor (TNF). Inhibition occurred at 1 ng/ml concentration of TGF beta. Also, TGF-beta dose-dependently suppressed cytotoxicity of TNF against L 929 cells, murine transformed fibroblasts. The concentration of TNF required for 50% cytolysis of L-929 cells was changed from 30 ng/ml to 350 ng/ml by 10 ng/ml TGF-beta. This suppression was abolished when L-929 cells were treated with actinomycin D or cycloheximide, suggesting that TGF-beta might inhibit the action of TNF via de novo protein synthesis. This response was not due to down regulation of TNF receptors nor to alteration of the affinity of TNF for its receptor. PMID- 2912447 TI - Increased dolichol content in glucocorticoid-sensitive human T-cell leukemia line grown in the presence of dexamethasone. AB - Two cell lines, derived from human T-cell acute leukemia, one glucocorticoid sensitive (CEM-C7) and the other glucocorticoid resistant (CEM-C1) were grown in the presence of 1 x 10-7 M dexamethasone and were analyzed for their dolichol content. After 24 hrs of incubation, dolichols became significantly elevated in the sensitive but not in the resistant line. Lovastatin, the specific inhibitor of cholesterol synthesis did not affect dolichol levels in either of the two cell lines. The results raise the possibility that dolichol accumulation might be involved in the early stages of the glucocorticoid-induced apoptosis (directed cell killing). PMID- 2912448 TI - Identification of the clathrin-binding domain of assembly protein AP-2. AB - The clathrin binding domain of the assembly protein AP-2 has been identified by proteolytically cleaving AP-2 into 2 discrete moieties, termed light and heavy mero-AP (LM-AP and HM-AP), and testing their ability to bind to clathrin assembled into cage structures or to clathrin trimers immobilized on Sepharose. The smaller product (LM-AP), which contains 20-40-kD fragments of the parent 100 kD polypeptides and which comprises two small appendages in the native AP-2 molecule, did not significantly interact with clathrin under either condition. In contrast, the HM-AP complex, which forms the larger central mass of the native AP 2 structure and contains uncleaved 50-kD and 16-kD polypeptides as well as 60-66 kD fragments of the parent 100-kD polypeptides, retained binding activity for both dissociated and assembled clathrin. PMID- 2912449 TI - Antibody-mediated targeting of differentiation inducers to tumor cells: inhibition of colonic cancer cell growth in vitro and in vivo. A preliminary note. AB - A differentiation inducer (sodium butyrate) encapsulated in liposomes that are in turn covalently linked to anti-Lex monoclonal antibody, SH1 (IgG3 isotype), was successfully targeted to human colonic adenocarcinoma HRT-18 and HT29 cells expressing Lex antigen in vitro as well as in vivo in athymic nu/nu mice. Tumor cell growth was significantly inhibited and was associated with changes in cell morphology and increases in membrane-bound alkaline phosphatase and gamma glutamyltranspeptidase, indicating the occurrence of butyrate-induced differentiation. PMID- 2912450 TI - Polyamines are sufficient to drive the transport of the precursor of ornithine carbamoyltransferase into rat liver mitochondria: possible effect on mitochondrial membranes. AB - The polyamines spermidine, spermine and putrescine, by themselves, at physiological concentrations, induce the transport of the precursor of ornithine carbamoyltransferase into isolated rat liver mitochondria. The presence of polyamines in the transport medium results in the approach of both mitochondrial membranes, suggesting a possible role of these molecules in the transport of the precursor of ornithine carbamoyltransferase into mitochondria, by the formation and/or stabilization of mitochondrial structures involved in the transport system. PMID- 2912451 TI - TPA- and agonist-induced force development in myometrium from pregnant and non pregnant rats. AB - In myometrium from pregnant rats, 100 nM-TPA elevated resting tension and initially slightly enhanced the contraction induced by 138 mM-KCl. After 20 min this force development significantly declined. In saponin-treated skinned myometrial cells from pregnant rats, 100 nM-TPA enhanced the contraction induced by 0.3 microM-Ca2+, but reduced that induced by 1 microM-Ca2+. These findings suggest that the excitatory and inhibitory actions of TPA on the myometrium are probably due to its action on the contractile proteins. In myometrium from non pregnant rats, TPA affected neither the resting tension, nor the amplitude of the evoked contractions, nor the Ca2+-induced contractions in skinned myometrium. While TPA only affected tension development in pregnant rats, both 1 mM-carbachol and 90 nM-oxytocin induced a tonic contraction in Ca-free solution independently of the hormonal status of the rats. The latter finding makes it unlikely that activation of protein kinase C is involved in the agonist-induced tonic force development in Ca-free solution. PMID- 2912452 TI - Tumor necrosis factor enhances replication of human immunodeficiency virus (HIV) in vitro. AB - The effect of tumor necrosis factor (TNF) on the replication of human immunodeficiency virus type 1 (HIV-1) was investigated in several T4 lymphocyte cell lines. TNF markedly enhanced the cytopathogenicity of HIV-1, virion associated reverse transcriptase (RT) activity in the cell culture supernatant, and viral antigen expression in MOLT-4 cells as early as 3 days after HIV-1 infection. A slight increase in RT activity was also observed in the supernatant of H9 cell cultures exposed to TNF. However, TNF did not increase either RT activity in MT-4 cell supernatants or viral antigen expression in HUT-78 cells. Thus, TNF is able to stimulate the replication of HIV-1 in de novo infected T4 cells although not all T4 cells seem to be sensitive to this stimulatory effect. PMID- 2912453 TI - alpha B subunit of lens-specific protein alpha-crystallin is present in other ocular and non-ocular tissues. AB - alpha-Crystallin, a tissue specific structural protein of the ocular lens, is known to be composed of two subunits, alpha A and alpha B. By using a specific antibody in an immunoblotting procedure we have found that one of the subunits, alpha B is present in a number of non-lenticular tissues including the retina, heart, skeletal muscle, skin, brain, spinal cord and lungs. Interestingly, in the rat, this protein is present in significantly higher concentrations in adult than in fetal tissues and, with the exception of the lens, fetal and adult heart has the highest concentration among the tissues examined. That the protein in question is, in fact, alpha B, was confirmed a) by the remarkable similarity of Staphylococcus aureus protease peptide maps of the protein in the heart and purified alpha-crystallin and b) by the sequence analysis of a rat heart cDNA clone identified by the alpha B antibody. Based on these observations we conclude that while alpha A has a tissue-specific role, alpha B is a polypeptide of independent function not restricted to the ocular lens. PMID- 2912454 TI - A novel citrulline-forming enzyme implicated in the formation of nitric oxide by vascular endothelial cells. AB - An enzyme in homogenates of porcine vascular endothelial cells forms L-citrulline from L-arginine. This enzyme is soluble and NADPH-dependent. In addition, the enzyme is inhibited by NG-monomethyl-L-arginine, suggesting that it is involved in the formation of nitric oxide by vascular endothelial cells. PMID- 2912455 TI - Staurosporine, a protein kinase C inhibitor, attenuates Ca2+-dependent stretch induced vascular tone. AB - The effects of protein kinase C inhibition by staurosporine was studied on Ca dependent tone of the rabbit facial vein. Tone was produced either by stretch or by readmission of Ca2+ in a non-depolarizing Ca2+-free salt solution. Stretch induced tone was inhibited by staurosporine. When tissues were incubated in a Ca2+-free solution, staurosporine (50 nM) inhibited the contractile responses produced by readmission of Ca2+. These observations suggest that maintenance of stretch-induced extracellular Ca2+-dependent tone may be regulated by protein kinase C. PMID- 2912456 TI - Antibody-antigen binding in organic solvents. AB - We describe, for the first time, the action of antibodies in anhydrous organic solvents. It has been demonstrated that the binding of a hapten, 4-aminobiphenyl, to the immobilized monoclonal antibody 2E11 is strong and specific not only in water but also in a variety of non-aqueous media. Further, the strength of interaction between antibody and hapten has been related to the hydrophobicity of the solvent: the more hydrophobic the solvent, the weaker the protein-ligand interaction. PMID- 2912457 TI - Treatment of chronic knee synovitis with arthroscopic synovectomy after failure of intraarticular injection of radionuclide. AB - Although satisfactory results have been obtained with conventional synovectomy of the knee, there are frequent complications, and a long period of rehabilitation is necessary after this surgery. We performed arthroscopic synovectomy of the knees of 30 patients (33 knees), 22 of whom had rheumatoid arthritis. These patients underwent the procedure after failure to respond to an intraarticular injection of either osmic acid or yttrium 90. The operated knee was moved 3-5 hours after the arthroscopy, and the patients walked the next day. No rehabilitation was needed. The followup period ranged from 6 months to 36 months, with an average of 17.7 months. Except for 1 patient with severe arthritis, all patients experienced improvement. Results were rated as "good" or "very good" in 27 knees. Six months after synovectomy, the patients were asked to rate their improvement; the mean +/- SEM degree of improvement was 79.1 +/- 22.9%. All patients had significant improvement in the range of motion of the knee. One patient required manipulation of the knee (while under anesthesia) soon after the arthroscopy. There were no other complications. There was no detectable radiographic evidence of disease progression in 24 patients who were seen 1 year after the procedure or in 9 patients who were seen 2 years after the arthroscopy. Thus, arthroscopic synovectomy appears to be an effective and simple treatment for chronic knee synovitis, and has a low morbidity rate. PMID- 2912458 TI - Arthroscopic synovectomy by rheumatologists: time for a new look. PMID- 2912459 TI - Folic acid treatment in methotrexate-treated rheumatoid arthritis patients: comment on the article by Furst and Kremer. PMID- 2912460 TI - Comment on the article by Weinblatt et al. PMID- 2912461 TI - Rheumatoid arthritis: rheumatoid factors, immune complexes, and C-reactive protein are raised shortly after the onset of symptoms. PMID- 2912462 TI - Multiple autoimmune diseases in a predisposed patient. PMID- 2912463 TI - Development and evaluation of a scale to measure perceived self-efficacy in people with arthritis. AB - There is evidence that the psychological attribute of perceived self-efficacy plays a role in mediating health outcomes for persons with chronic arthritis who take the Arthritis Self-Management Course. An instrument to measure perceived self-efficacy was developed through consultation with patients and physicians and through study of 4 groups of patients. Tests of construct and concurrent validity and of reliability showed that the instrument met appropriate standards. Health outcomes and self-efficacy scores improved during the Arthritis Self-Management Course, and the improvements were correlated. PMID- 2912464 TI - Insulin-like growth factor stimulation of chondrocyte proteoglycan synthesis by human synovial fluid. AB - We investigated the role of insulin-like growth factors (IGFs) as regulating factors of cartilage metabolism in human synovial fluid (SF), using a bovine explant culture system that was shown to respond to recombinant IGF-1 in vitro. SF from rheumatoid arthritis (RA) patients and from control patients was found to stimulate chondrocyte proteoglycan synthesis in bovine articular cartilage. A monoclonal antibody directed primarily against IGF-1 (and to some extent, IGF-2) partially blocked the stimulatory action of serum and totally blocked the stimulation by SF. These findings indicate that IGFs are major regulating factors of cartilage proteoglycan synthesis in human SF. In addition, we measured serum and SF levels of IGF-1 in RA patients and control patients, using a radioimmunoassay. No difference in immunoreactive serum IGF-1 was detected between patients and controls. The IGF-1 levels in SF were consistently lower than in serum, for both patient groups. No differences in IGF-1 concentration were found between RA and non-RA SF. The relevance of these data with respect to joint inflammation is discussed. PMID- 2912465 TI - Relative role of genetic and environmental factors in disease expression: sib pair analysis in ankylosing spondylitis. AB - Forty-two sib pairs concordant for ankylosing spondylitis (mean disease duration 20.1 years) were assessed to define the relative role of genetic and environmental factors in determining age and calendar year of disease onset, systemic features, functional outcome and prognosis, and radiologic progression. Twenty-seven pairs were of the same sex (male/male n = 21, female/female n = 6). The correlation coefficient was not significant for age at onset (rs = 0.235), but was much higher for calendar year of onset (rs = 0.702, P less than 0.01). These data were confirmed by two-way analysis of variance: between sibs, the F probability was 0.07 for age at onset (41 degrees of freedom, F ratio 1.6) and was less than 0.001 for calendar year of onset (41 degrees of freedom, F ratio 5.45). Thus, it is suggested that environmental factors play the greater role in the timing of onset. Concordance for the presence or absence of uveitis was only 43%, again suggesting that genetic factors are less significant than the environment. Conversely, genetic factors are more important in influencing prognosis. A disability and pain index revealed that sibs had a closer score than expected by chance alone (P = 0.035); also, the correlation coefficient for blinded radiologic analysis (pelvic and lumbar views) was significant for pairs of sibs (rs = 0.859, P less than 0.01), but was not significant for random pairs of subjects (rs = -0.144). In contrast, within-sib pair and random subject-pair analyses of hip radiographs revealed rs = -0.111 and -0.033, respectively, neither of which was significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2912466 TI - Sensitivity, specificity, and predictive value of abdominal fat aspiration for the diagnosis of amyloidosis. AB - Samples of abdominal fat aspirates from 73 patients were sent to us for staining and interpretation. Ten samples were positive for amyloid. We calculated the sensitivity, specificity, and predictive value of the procedure based on the findings and the clinical information and other biopsy data about these patients. Using the results from more traditional biopsies as the "gold standard," sensitivity was 57%, specificity was 100%, and the predictive value was 100% for positive findings in the abdominal fat aspirate. Although the sample size in this study was relatively small, the procedure was found to be a minimally invasive test of high clinical utility. PMID- 2912467 TI - The beneficial outcomes of the arthritis self-management course are not adequately explained by behavior change. AB - Evaluation of the Arthritis Self-Management Course revealed significant positive changes in the practice of behaviors that were taught and in health outcomes. However, utilizing a variety of statistical techniques, we were able to demonstrate only weak associations between changes in behavior and changes in health status. This suggests the need to examine the mechanisms by which health education affects health status. PMID- 2912468 TI - Eosinophilic fasciitis in a pair of siblings. AB - Two siblings, a 38-year-old woman and a 33-year-old man, developed eosinophilic fasciitis within a period of 6 months. They were found to have identical HLA-A, B, DR, and DQ antigens, raising the possibility of a genetic influence in the development of this disease. No common environmental factors close to the time of onset were identified; however, the possibility of a common, remote environmental factor cannot be discounted. PMID- 2912469 TI - Comparison of the geometric and the contrast models of similarity by presentation of visual stimuli to the left and the right visual fields. AB - In this study we investigated by means of the "same-different" decision task the process of comparing visual stimuli (schematic faces, familiar objects, houseplants, and nonsense figures) when presented for 100-150 msec to the right or to the left visual hemifields. The analysis of incorrect "same" responses showed that the addition of a common component (e.g., glasses, buttons) to a pair of nonidentical stimuli increased the percentage of incorrect same responses whereas the addition of the same component to one stimulus only in the pair decreased the percentage of incorrect "same" responses. This pattern, which is in accordance with Tversky's contrast model of similarity, is incompatible with any geometric model. Second, for schematic faces the results revealed that the left hemisphere is more sensitive to common than to distinctive features, whereas the right hemisphere is more sensitive to distinctive than to common features. No such interaction was obtained for the other type of stimuli. The implications of these results for models of similarity and the difference between the present findings and the findings of Sergent (1984) are discussed. PMID- 2912470 TI - Evidence for cerebral asymmetries in a finger sequencing task. AB - Visual input was lateralized using a specially designed contact lens system. Subjects performed a sequence of two keypresses in response to a light stimulus with either the left or the right hand in a choice reaction time paradigm. Two choice reaction time conditions were used: (A) hand certainty, sequence uncertainty and (B) hand uncertainty, sequence certainty. Reaction time (RT) results indicate that there are no significant differences between the left and right hemisphere in selecting a sequential response in either of the two conditions. Interfinger time (IFT) results show a relative left eye (right hemisphere)-left hand advantage when there was hand certainty, sequence uncertainty and a relative left eye (right hemisphere) disadvantage for both hands when there was hand uncertainty, sequence certainty. The RT results do not support the concept of a center in the left hemisphere for selection of the components of a two-element sequential keypress, prior to movement initiation. However, the IFT results indicate that there are differences in the processing ability of the left and right hemispheres in a sequencing task, after movement initiation. PMID- 2912471 TI - Hemispheric asymmetries in interpreting forms vs colors in ambiguous patterns. AB - Prior to receiving briefly lateralized presentations of ambiguous visual patterns (Rorschach inkblots), 28 normal right-handed males heard two words, each describing a different interpretation of the pattern, e.g., one word might describe an interpretation based on attending to shapes or forms (form choices) and the other might describe an interpretation based on attending to chromatic color (e.g., color choices). Color choices were more frequent than form choices on left-hemisphere (LH) presentations of the patterns, and form choices were more frequent than color choices on right-hemisphere (RH) presentations. These results were interpreted as consistent with the theory that the LH's favored mental representation is semantic (i.e., frequent choices of concepts associated with names of colors in the patterns) and the RH's favored representation is imaginal (i.e., frequent choices of concepts associated with difficult-to-label forms in the patterns). PMID- 2912472 TI - Stimulus intensity, attentional instructions, and the ear advantage during dichotic listening. AB - The present experiment was designed to investigate the effects of the following two variables on the identification of dichotically presented CV syllables: (1) the relative difference in intensity levels of the stimuli presented to the two ears and (2) the instructions to attend to both ears or to focus attention on one ear. As expected for a verbal task, more CV's were identified from the right ear than from the left ear. Furthermore, identification of stimuli presented to one ear improved when (1) those stimuli were relatively higher in volume than the stimuli presented to the other ear and (2) when subjects were instructed to focus attention on only that ear rather than distribute attention across both ears. Of particular importance is the finding that the effects of relative stimulus intensity are the same under conditions of focused attention as under conditions of divided attention. This finding is inconsistent with an attention explantation of the relative intensity effects. Instead, the results are consistent with a model of dichotic listening in which ear of stimulus presentation and relative stimulus intensity influence a perceptual stage of information processing and attentional instructions influence a subsequent response selection stage. PMID- 2912473 TI - Childhood prosopagnosia. AB - K.D. has been unable to recognize people's faces since sustaining cerebral injury in infancy. Investigation of this disorder carried out when K.D. was aged 8 to 11 years showed that although her basic visual abilities were impaired, they were no poorer than those of other children who recognized faces without difficulty. K.D. had learned to read, but had not regained ability to recognize people's faces; instead she relied primarily on voices as a cue to person recognition. There was no evidence of any degree of overt or covert recognition of familiar faces, and K.D. also experienced problems in visual object recognition. She could, however, classify a visual input as a face, was able to perceive and imitate facial expressions, and was able to perform face matching tasks to an extent limited by her use of a feature by feature matching strategy. It is suggested that K.D.'s impairment affected higher order perceptual abilities, and is in a number of respects comparable to the impairments found in adult prosopagnosic patients. PMID- 2912474 TI - Duplex perception: some initial findings concerning its neural basis. AB - Duplex perception is the simultaneous perception of a speech syllable and of a nonspeech "chirp," and occurs when a single formant transition and the remainder (the "base") of a synthetic syllable are presented to different ears. The current study found a slight but nonsignificant advantage for correct labeling of the fused syllable when the chirp was presented to the left ear. This advantage was amplified in the performance of a "split-brain" subject. A subject with a left pontine lesion performed at chance level when the chirp was presented to her left ear. These findings suggest that some, if not complete, ipsilateral suppression does occur in the dichotic fusion procedure, and that identification of the fused syllable is maximal when the left hemisphere fully processes the linguistic characteristics of the base (through contralateral presentation), and at least minimally processes the frequency transition information of the chirp (through ipsilateral presentation). PMID- 2912475 TI - Selective spatial attention and length representation in normal subjects and in patients with unilateral spatial neglect. AB - The aim of this study was to assess whether perceptual representation along the horizontal axis is affected by hemispace position of the stimulus or by orienting attention to one side. Ten control subjects and 10 right brain damaged patients with left unilateral spatial neglect (USN) were asked to bisect lines of five lengths in three space positions (left, center, right) and under three cueing conditions (no cue, left cue, right cue). Normal controls showed significant displacement of bisection opposite to the side of hemispace presentation and toward the side of cueing. USN patients showed a bisection error toward the right end which increased with lines placed in the left hemispace and decreased with lines placed in the right hemispace and when attention was oriented toward the left side. We conclude that (1) In absence of cues normal subjects tend to overestimate the portions of space closer to their body midline; (2) both normal and USN patients tend to overestimate portions of space that they direct their attention to; (3) USN patients' performance without cueing is consistent with an attentional shift toward the right hemispace implying a gradient of overestimation of the right-most portions of space. A common neural substratum for directing attention and space representation can explain these findings. PMID- 2912476 TI - Memory for action events in Alzheimer-type dementia: further evidence of an encoding failure. AB - The purpose of the present research was to examine the nature of the encoding problem in patients with dementia of the Alzheimer type (DAT) using a nonstrategic memory task, namely the recall of action events or subject-performed tasks (SPTs). The first experiment investigated the retention of SPTs and the verbal descriptions of action events in patients with mild-to-moderate DAT, young, and old adults. While the healthy older adults showed significantly higher recall for SPTs than for verbal descriptions, the DAT patients failed to exhibit this effect. A follow-up study replicated this same pattern using SPTs and tasks performed by the experimenter. As the multimodal and contextually rich encoding environment present in SPTs had no effect on the patients' retention, this suggests that manipulations designed to enhance encoding in this population will be unsuccessful. The relevance of the results to (1) memory compensation in the aged, and (2) the development of mnemonic training programs for the elderly are discussed. PMID- 2912477 TI - Memory for internally generated words in Alzheimer-type dementia: breakdown in encoding and semantic memory. AB - The "generation effect" is a phenomenon in which words that are generated by the subject are remembered better than words which are read. The present experiments examined this effect in patients with mild-to-moderate dementia of the Alzheimer type (DAT), healthy elderly adults, and young adults under a variety of different encoding and retrieval conditions. Experiment 1 employed an intentional learning task with multiple study/test trials using the same list of words. While both the young and elderly adults exhibited higher recall for internally generated words than read words, the DAT patients failed to demonstrate the effect even after repeated exposures to the same stimulus list. Experiment 2 replicated this same pattern of results using an incidental learning paradigm with both recall and recognition tests. Various explanations as to why the DAT patients failed to show the generation effect were discussed with particular emphasis placed on the role of semantic memory and encoding failure. PMID- 2912478 TI - Permeability studies on protective gloves used in dental practice. AB - The recent guidelines issued by the DHSS and the BDS recommend that to prevent cross-infection gloves should be worn by dentists and their assistants whilst treating all patients. Little information is available on the permeability of the various types of glove available; this pilot study was therefore conducted, to test five commonly used brands of gloves for permeability to air, electrolytes, dye and bacteria. Tests were carried out before and after using the gloves for varying periods. From these studies it was found that only one brand of glove passed all the tests before wearing. After wearing the gloves for up to 3 hours, between 20% and 50% of the gloves, depending on type, allowed bacteria to pass across the glove. The visual test was less critical than the ion passage and bacterial tests, in that some gloves without obvious perforations allowed ions and bacteria to pass through. PMID- 2912479 TI - Acute herpetic stomatitis: referrals to Leeds Dental Hospital 1978-1987. AB - The clinical data of 102 patients referred to Leeds Dental Hospital from 1978 to 1987 with acute herpetic stomatitis confirmed by laboratory investigations were analysed. No gender difference was found. Differences in age distribution were marked. Only 5% of patients were aged less than 11 years, whereas the majority of cases (51%) occurred during the third decade. Statistical analysis confirmed a general trend for the mean age of patients to have increased progressively over the 10-year period. PMID- 2912480 TI - Psychiatric disorders in a dental clinic. AB - This paper describes the psychiatric disorders seen in 138 consecutive attenders at a psychiatric clinic in a dental hospital. The disorders were rated using a standardised interview, and assigned a diagnosis in accordance with a multiaxial classification known as the DSM-III. The rate of psychiatric disorder seen in these patients was over 90% and the implications of this are discussed. PMID- 2912481 TI - Resorption of a first permanent molar. AB - A case is presented of an unerupted maxillary second premolar causing the severe resorption of a first molar tooth. This case underlines the need for adequate radiographic evidence before recommending the extraction of teeth for the relief of crowding. PMID- 2912482 TI - Beginning to work together. AB - Ten people met for the first time as trainees after lunch on Thursday, 4 February, 1988 at an hotel near Ipswich. They were to live and work together until teatime on Saturday. Twelve trainers joined them from late afternoon on Friday, staying on after the trainees left, until lunchtime on the Sunday. The occasion was the start of the 1988 vocational training schemes for East Anglia and North East Thames Regions. In this article, J. K. Horrocks and W. R. Allen given an account of what happened during this time, and how people felt about it. PMID- 2912483 TI - Community orthodontic services: a local review. AB - A review is presented of orthodontic treatment and working conditions in one area of the Community Dental Service over a typical period of one year (1984). Treatment totals, case load, working facilities and schedules are discussed, drawing comparisons with the hospital service and specialist practice and with previously published surveys of orthodontics in the community service. An estimate of the size of school population likely to support a full-time community orthodontist is made together with the number of referring practitioners. Comments are also made on the range of treatment provided, patients' attitudes, cooperation and such problems as missed appointments. A short section is devoted to actual timings of specific procedures in orthodontics, followed by discussion of the hospital attachment for community orthodontists, with some recommendations on working conditions and comments on career structure. PMID- 2912484 TI - Spare a thought for the resident hospital dental surgeon. PMID- 2912485 TI - Remuneration for oral mucosa screening. PMID- 2912486 TI - 'Dental sedation. A review'. PMID- 2912488 TI - Relativity theory for dentists. PMID- 2912487 TI - Cash incentive for MCCD qualifier. PMID- 2912489 TI - Unprofessional conduct. PMID- 2912490 TI - Observations on the substrate specificity of prostaglandin hydroxylases of monkey seminal vesicles and sheep vesicular glands. AB - Prostaglandin (PG) 19-hydroxylase of monkey seminal vesicles metabolizes PGE1 and PGE2 to their 19-hydroxy metabolites, while PGE2 20-hydroxylase of ram vesicular glands metabolizes PGE2 to 20-hydroxy-PGE2. The purpose of the present study was determine whether PGF2 alpha is a substrate of these enzymes. Deuterated 20 hydroxy-PGF2 alpha was employed as an internal standard to study the hydroxylation of PGF2 alpha (0.2 mM) by microsomes of monkey (Macaca fascicularis) seminal vesicles in the presence of NADPH, and the biosynthesis was compared with the hydroxylation of PGE2 under identical conditions. 19-Hydroxy PGF2 alpha was formed at a rate of 3.5% of the formation of 19-hydroxy-PGE2. Microsomes of ram vesicular glands also hydroxylated PGE2 more efficiently than PGF2 alpha, which was converted to both 20-hydroxy-PGF2 alpha and 19-hydroxy-PGF2 alpha at a combined rate of 5% of the biosynthesis of 20-hydroxy-PGE2 under the same conditions. 20-Hydroxy-PGF2 alpha was demonstrated in ram semen, but the concentration was low (0.1 microM) in comparison with 20-hydroxy-PGE2 (24 microM). The two genital PG hydroxylases thus metabolize PGF2 alpha much less efficiently than PGE2. This finding may suggest that 19-hydroxy- and 20-hydroxy PGF2 alpha in seminal fluids also could be formed by other mechanisms, e.g., from 19-hydroxy- and 20-hydroxy-PGE2 by the PGE 9-keto reductase enzyme. PMID- 2912491 TI - Altered acyl chain compositions of alkylacyl, alkenylacyl, and diacyl subclasses of choline and ethanolamine glycerophospholipids in rat heart by dietary fish oil. AB - The effects of dietary fish oil containing n - 3 polyunsaturated fatty acids on the fatty acid compositions of the alkylacyl and alkenylacyl species of choline glycerophospholipids (CGP) and ethanolamine glycerophospholipids (EGP) were studied in rat heart and compared with the corresponding diacylglycerophospholipids. After a 7 week feeding period, all phospholipid classes from the fish oil group exhibited much higher levels of the n - 3 polyunsaturated fatty acids including eicosapentaenoic acid (20:5(n - 30)), docosapentaenoic acid (22:5(n - 3)) and docosahexaenoic acid (22:6(n - 3)), as well as lower levels of the n - 6 series (18:2, 20:4, 22:4 and 22:5), relative to animals given sunflower seed oil-enriched in 18:2(n - 6). However, the docosahexaenoic acid rather than eicosapentaenoic acid provided a much greater contribution to the n - 3 accumulation (fish oil group) in the ether-containing CGP, as indicated by the 20:5(n - 3)/22:6(n - 3) molar ratios of 0.32, 0.26 and 0.56 in the alkylacyl, alkenylacyl and diacyl classes, respectively. In addition to accumulating very high levels of docosahexaenoic acid (e.g., 47.2 mol% of fatty acids in alkenylacylglycerophosphoethanolamine of fish oil group), both ether-linked classes of EGP exhibited significantly higher levels of docosapentaenoic acid than the diacylglycerophosphoethanolamine (GPE) and all classes of CGP. These findings may bear relevance to possible beneficial effects of dietary fish oil on pathophysiological states (including myocardial ischemia) in cardiac tissue and their mediation via platelet-activating factor, 1-alkyl-2 acetylglycerophosphocholine (PAF) and arachidonic acid (20:4(n - 6))-derived eicosanoids. PMID- 2912492 TI - Interaction of lipid peroxidation products with nuclear macromolecules. AB - The interaction of lipid peroxidation products with nuclear macromolecules was investigated in rat liver nuclei labelled with [3H]arachidonic acid. Lipid peroxidation reactions were driven both non-enzymatically and enzymatically by the addition of ascorbate-Fe2+ or NADPH-ADP-Fe3+, respectively, to the incubation mixtures. The extent of peroxidation was evaluated by the formation of thiobarbituric acid chromophore and of radioactive hydrophilic peroxidation products. The results obtained show that: (1) nuclear membrane lipid peroxidation products formed during incubation interact with DNA and total nuclear proteins; (2) non-enzymatic lipid peroxidation processes induced a 40% larger association of peroxidation products to DNA compared to processes driven enzymatically, whereas the corresponding interaction with total nuclear proteins was similar in both peroxidation systems; (3) the radioactivity associated with histones decreased during incubation in the presence of ascorbate-Fe2+ or NADPH-ADP-Fe3+, and increased in control samples (no additions); (4) inhibition of lipid peroxidation by the iron chelator Desferrioxamine B prevented the association of peroxidation products to nuclear macromolecules; (5) the levels of radioactivity found in DNA after 180 min of incubation would represent the formation of 0.6-1.0 adducts per 10(6) DNA bases. The results obtained provide evidence for an interaction between lipid peroxidation products and chromatin in the interior of the cell nucleus. PMID- 2912493 TI - Circulating and liver-bound salt-resistant hepatic lipases in the golden hamster. AB - The serum of male golden hamsters was found to contain a circulating triacylglycerol hydrolase activity (serum lipase). In vitro, the enzyme activity was slightly activated by 1 M NaCl (+20%) and inhibited by rat serum (-29%). The hamster liver contained an enzyme with similar characteristics (liver lipase). This enzyme was released into the circulation after intravenous administration of heparin. Both lipase activities were further characterized and compared. The serum lipase had a pH optimum of 9, which was higher than that of the liver enzyme (pH 8.0). The serum enzyme did not bind to Sepharose-heparin columns in contrast to the liver lipase, which could be eluted from the column with 0.75 M NaCl. A polyclonal antibody preparation raised against the heparin-releasable salt-resistant lipase from rat liver inhibited both the hamster serum enzyme and the liver enzyme completely. The affinity of the antibodies towards the hamster enzymes was lower than the affinity towards the rat liver enzyme, but similar with that towards the hamster enzymes in the serum and the liver. A panel of five monoclonal antibodies raised against the rat enzyme did not bind either of the hamster enzymes. If the hamsters were fed a normal lab chow, the lipase activity in the serum amounted up to 110 +/- 20 mU (mean +/- S.D., n = 16) per ml serum (about 600 mU per animal), the liver contained 200 +/- 41 mU per g tissue (total about 800 mU per animal). In animals fed a cholesterol-enriched diet, the serum activity increased by 82% and the liver activity by 27%. PMID- 2912494 TI - Polar lipids and fatty acids of Pseudomonas cepacia. AB - The polar lipids and fatty acids produced by the reference strains for seven different O serogroups of Pseudomonas cepacia have been identified. Similar results were obtained for all strains. Contrary to a previous report, the only significant phospholipids in this species are phosphatidylethanolamine and bis(phosphatidyl)glycerol, which contributed 57-83% and 17-43%, respectively, of the total lipid phosphorus. The former lipid was found as two chromatographically distinct fractions. In the less polar fraction and in bis(phosphatidyl)glycerol, the major fatty acids were hexadecanoic acid, cis-9,10-methylenehexadecanoic acid, cis-octadec-11-enoic acid, and cis-11,12-methyleneoctadecanoic acid. In the more polar fraction of phosphatidylethanolamine, the fatty acid in one position is a 2-hydroxy acid, mainly 2-hydroxyhexadecenoic acid, 2-hydroxyhexadecanoic acid, 2-hydroxyoctadecenoic acid, or 2-hydroxymethyleneoctadecanoic acid. Compared with other phospholipids, this fraction of phosphatidylethanolamine was depleted in cis-9,10-methylenehexadecanoic acid. Each strain also produced two ornithine amide lipids. In the major lipid, 3-hydroxyhexadecanoic acid was amide bound to the alpha-amino group and was itself probably esterified by a 2-hydroxy acid, mainly 2-hydroxyoctadecenoic acid or the derived cyclopropane acid. In the minor ornithine amide lipid, the ester-bound acids were mainly methyleneoctadecanoic acid and hexadecanoic acid. The unusual lipid profiles of P. cepacia are of chemotaxonomic interest. PMID- 2912495 TI - Formation of bis(monoacylglycero)phosphate by a macrophage transacylase. AB - Formation of bis(monoacylglycero)phosphate (BMP) from lysophosphatidyl[U 14C]glycerol was studied in rabbit pulmonary alveolar macrophages. The majority of the activity was found in the particulate fraction (lysosome-enriched) sedimenting between 2000 and 12,000 rpm and it was maximal at pH 4.5. The activity in this fraction was stimulated by 2-mercaptoethanol and additional lipids from the fraction and inhibited by 5 mM CaCl2, 0.5 mM acyl-CoA, 1.0 mM chlorpromazine and by detergents, whereas chloroquine, cholesterol and butanol had no effect. The activity was retained by the particles after repeated freezing and thawing. After treatment with n-butanol, most of the activity was lost, but 84% could be recovered in the aqueous phase if the butanol-extracted lipids were added back giving an activity of 266 nmol/h per mg of protein. Lipids most effective in restoring activity were the total lipids extracted by butanol from the particulate fraction, fractions of the total lipids containing phospholipids and phosphatidylcholine from both native and commercial sources, with native BMP and commercial phosphatidylglycerol and sphingomyelin having a much smaller effect. The complexity of the lipid requirements was further indicated by the finding that addition of pure lipids to the total lipid extract reduced the efficacy of the latter. A direct transfer of [14C]oleic acid to BMP from labelled macrophage microsomal lipids was catalyzed by the soluble enzymes as was transfer from dioleoylphosphatidylcholine in the presence of lysophosphatidylglycerol. The particulate enzyme also catalyzed the transfer of [14C]oleic acid from 2 oleoylphosphatidylcholine to BMP in the presence of lysophosphatidylglycerol. These findings indicate that the transacylase involved in conversion of lysophosphatidylglycerol to BMP utilizes complex lipids other than phosphatidylinositol as acyl donors and has complex requirements for lipids as physicochemical activators. They further suggest that the transacylation might be catalyzed by lysosomal phospholipase A2. PMID- 2912496 TI - Stimulation of surfactant secretion by vasopressin in primary cultures of adult rat type II pneumocytes. AB - The current study examined the effect of vasopressin on the secretion of phosphatidylcholine, the principal component of pulmonary surfactant, from adult rat alveolar type II pneumocytes in primary culture. Vasopressin stimulated secretion in a time- and dose-dependent manner. At a concentration of 10 nM, vasopressin stimulated release by 6-fold over the basal secretory rate. The concentration producing half the maximal response for vasopressin-induced secretion was 0.4 nM. The stimulation of phosphatidylcholine release by vasopressin was duplicated by the vasopressin fragment, amino acids 4 through 9. [Lys8]vasopressin and the selective vasopressin-2 agonist [deamino-8-D Arg]vasopressin did not stimulate surfactant secretion effectively. The vasopressin- and fragment-induced secretion was inhibited by the vasopressin-1 receptor antagonist d(CH2)5TDAVP and the protein kinase C inhibitor, tetracaine, but not by the beta-adrenergic antagonist alprenolol. Vasopressin did not activate adenylate cyclase, which suggests that stimulation by vasopressin was independent of cyclic AMP. When vasopressin and isoproterenol were added concomitantly, the effects on phosphatidylcholine secretion were additive. This suggests that these two secretagogues operate via separate mechanisms. PMID- 2912497 TI - Prostaglandin-E2 9-ketoreductase from swine kidney. Production of antisera and application to development of a radioimmunoassay. AB - Prostaglandin-E2 9-ketoreductase (PGE2-9-KR, EC 1.1.1.189), the enzyme which catalyzes the reaction from prostaglandin E2 (PGE2) to prostaglandin F2 alpha (PGF2 alpha), was purified 580-fold from swine kidney. The molecular mass of the enzyme determined by SDS-gel electrophoresis was 33 kDa. Antiserum against the purified enzyme was raised in three rabbits. The antiserum was able to precipitate PGE2-9-KR from swine kidney and to crossreact with pGE2-9-KR from several reproductive organ tissues, such as rabbit ovary, rabbit corpus luteum, rabbit endometrium and human decidua vera. When swine kidney PGE2-9-KR was labelled with 125I and incubated with affinity-purified antiserum in the presence of increasing amounts of unlabelled enzyme, competitive binding of the unlabelled enzyme to the antibody was observed. A radioimmunoassay for the quantitation of the enzyme was developed. The standard curve was linear from 5 to 500 ng enzyme. The intra- and interassay coefficients of variation were 6.4 and 13.2%, respectively. The assay may be useful for the quantitation of PGE2-9-KR in several tissues under various physiological conditions. PMID- 2912498 TI - Synthesis, modification, and flotation properties of rat hepatocyte apolipoproteins. AB - We have studied apolipoprotein synthesis, intracellular modification and secretion by primary adult rat hepatocyte cultures using continuous pulse or pulse chase labeling with [35S]methionine, immunoprecipitation and two dimensional isoelectric focusing/polyacrylamide gel electrophoresis. The flotation properties of the newly secreted apolipoproteins were studied by discontinuous density gradient ultracentrifugation and one- and two-dimensional polyacrylamide gel electrophoresis. These studies showed that rat hepatocyte apoE is modified intracellularly to produce minor isoproteins that differ in size and charge. One of these minor isoproteins represents a monosialated apoE form (apoE3s1). Similarly, apoCIII is modified intracellularly to produce a disialated apoCIII form (apoCIIIs2), whereas newly synthesized apoA-I and apoA-IV are not glycosylated and overlap on two-dimensional gels with the proapoA-I and the plasma apoA-IV form, respectively. Both unmodified and modified apolipoproteins are secreted into the medium. Separation of secreted apolipoproteins by density gradient ultracentrifugation has shown that 50% of apoE, 80% of apoA-I, and more than 90% of apoA-IV and apoCIII are secreted in a lipid-poor form, whereas apoB 100 and apoB-48 are 100% associated with lipids. ApoB-100 floats in the VLDL and IDL regions, whereas apoB-48 is found in all lipoprotein fractions. ApoE and small amounts of apoA-I, apoA-IV and apoCIII float in the HDL region. Small amounts of apoE and apoCIII are also found in the VLDL and IDL regions, and apoE in the LDL region. Ultracentrifugation of nascent lipoproteins in the presence of rat serum promoted flotation of apoA-I and apoA-IV in the HDL fraction and resulted in increased flotation and distribution of apoE and apoCs in VLDL, IDL and LDL regions. These observations are consistent with the hypothesis that intracellular assembly of lipoproteins involves apoB-48 and apoB-100 forms, whereas a large portion of apoA-I, apoCIII and apoA-IV can be secreted in a lipid poor form, which associates extracellularly with preexisting lipoproteins. PMID- 2912499 TI - Nonenzymatically glycated serum albumin: interaction with galactose-specific liver lectins. AB - The possible interaction of galactose/glucose-specific liver lectins with nonenzymatically glycated human serum albumin was analyzed. The binding activity of the asialoglycoprotein receptor on hepatocytes and of the corresponding lectin on Kupffer cells was determined using freshly isolated liver cells from Wistar rats. Nonenzymatically glucosylated or galactosylated human serum albumin (HSA) did not inhibit lectin binding in a competitive adhesion assay (less than 15% inhibition). In contrast, lactosylated HSA strongly interacted with the two liver lectins (more than 80% inhibition). Lectin binding increased with lactosylation reaching a maximum at 44-49 mol D-galactose bound per mol HSA. In conclusion, at least in certain cases, nonenzymatically glycated proteins may interact with endogenous lectins. PMID- 2912501 TI - Parathyroid hormone degradation by chymotrypsin-like endopeptidase in the clonal osteogenic UMR-106 cell. AB - Parathyroid hormone (PTH) -degrading activity was studied using osteoblast-like UMR-106 cells. PTH-degrading activity was assessed by the amount of PTH fragments produced in the medium after exposure of intact human PTH-(1-84) to UMR-106 cells. PTH immunoreactivity recovered in trichloroacetic acid-soluble products of the medium and in fractions eluted from reverse-phase high-performance liquid chromatography (HPLC) was measured by radioimmunoassay using an antibody specific for the mid-region and C-terminus of PTH. In this study, intact UMR-106 cells but not extracellular enzymes cleaved human PTH(1-84) into fragments which were released into the medium (in a time- and temperature-dependent fashion). HPLC analysis of the PTH fragments depicted three immunoreactive peaks (peaks 1, 2 and 3) besides intact PTH, indicating a limited PTH-hydrolyzing activity of the cells. Furthermore, a 1000-fold molar excess of either hPTH-(3-34) or [Nle8,Nle18,Tyr34]hPTH-(3-34)amide inhibited PTH-degrading activity by 63% and 80% of control, respectively, whereas neither calcitonin, vasopressin nor growth hormone suppressed it. Additionally, HPLC analysis of the samples treated with [Nle8,Nle18,Tyr34]hPTH-(3-34)amide showed a reduction of the three peaks, suggesting an involvement of PTH receptor in the production of PTH fragments. This PTH-degrading activity was strongly inhibited by phenylmethylsulfonyl fluoride and chymostatin, but not by soybean trypsin inhibitor, elastatinal or inhibitors of cysteine, aspartic or metalloproteinases, indicating that it is due to a seryl chymotrypsin-like endopeptidase. Chymotrypsin-like activity seems to be solely responsible for PTH-degrading activity in intact UMR-106 cells, since all three PTH fragments were predominantly suppressed in the presence of chymostatin. Further analysis of chymotrypsin-digested products of hPTH-(1-84) eluted from HPLC exhibited five fragments detected by ultraviolet absorbance at 210 nm, three of which were measurable by PTH radioimmunoassay, each corresponding to the three PTH fragments produced by UMR-106 cells. To explore the cleavage sites of PTH further, amino acid analysis of chymotrypsin-cleaved products was performed. The results strongly support the view that the chymotrypsin-like enzyme in UMR-106 cells cleaved the hormone between residues 23 24 and 34-35, to produce, at least, hPTH-(24-84) and -(35-84). Our present study indicates that a chymotrypsin-like endopeptidase is solely responsible for limited hydrolysis of PTH by intact UMR-106 cells. PMID- 2912500 TI - The cyanogen bromide fragment I of asialoorosomucoid is transported more efficiently than asialoorosomucoid in rat hepatocytes. AB - Cultured rat hepatocytes internalized and degraded 125I-labeled asialoorosomucoid (125I-ASOR) through asialoglycoprotein receptor at rates about half that of its cyanogen bromide fragment I (125I-ASCNBr-I). Reduction and carboxymethylation of the fragment resulted in decreased rates of internalization and degradation which were still greater than those of 125I-ASOR. In the presence of 5 microM colchicine, degradation of all three ligands was inhibited. However, the intracellular level of 125I-ASOR at steady state remained unchanged, while those of the fragments increased continuously. Study of the binding of these ligands to hepatocytes at 4 degrees C indicated that there was no significant difference in binding parameters between ASOR, ASCNBr-I and RC-ASCNBr-I (reduced and carboxymet ASCNBr-I). Studies of the fate of these ligands preloaded in the cell at 37 degrees C indicated that a higher fraction of the internalized ASOR than of the fragments was released by diacytosis. In contrast to ASOR, diacytosis of the fragments was not enhanced by colchicine. Studies of the distribution of intracellular ligands by Percoll density gradient centrifugation indicated that they were internalized initially into two early endosomal compartments of d = 1.037 g/ml and d = 1.045 g/ml. In the presence of colchicine, accumulation of the ligands in a third endosomal compartment of d = 1.08-1.095 g/ml was revealed, while in the presence of leupeptin accumulation of the ligands in lysosomes was observed. The results of a kinetic analysis indicated that both cyanogen bromide fragments were transported to all these compartments more rapidly than was ASOR. It appears that they are internalized and degraded more rapidly than ASOR due to a more efficient sorting of the internalized ligand into the pathway of lysosomal degradation. PMID- 2912502 TI - Uptake of ferritin and iron bound to ferritin by rat hepatocytes: modulation by apotransferrin, iron chelators and chloroquine. AB - Rat liver ferritin is an effective donor of iron to rat hepatocytes. Uptake of iron from ferritin by the cells is partially inhibited by including apotransferrin in the culture medium, but not by inclusion of diferric transferrin. This inhibition is dependent on the concentration of apotransferrin, with a 30% depression in iron incorporation in the cells detected at apotransferrin concentrations above 40 micrograms/ml. However, apotransferrin does not interfere with uptake of 125I-labeled ferritin, suggesting that apotransferrin decreases retention of iron taken up from ferritin by hepatocytes by sequestering a portion of released iron before it has entered the metabolic pathway of the cells. The iron chelators desferrioxamine (100 microM), citrate (10 mM) and diethylenetriaminepentaacetate (100 microM) reduce iron uptake by the cells by 35, 25 and 8%, respectively. In contrast, 1 mM ascorbate increases iron accumulation by 20%. At a subtoxic concentration of 100 microM, chloroquine depresses ferritin and iron uptake by hepatocytes by more than 50% after 3 h incubation. Chloroquine presumably acts by retarding lysosomal degradation of ferritin and recycling of ferritin receptors. PMID- 2912503 TI - Phosphorus-31 and water proton relaxation in living erythrocytes. Application to uremia. AB - We measured the spin-lattice and spin-spin relaxation times (T1 and T2, respectively) and the nuclear Overhauser effect (NOE) of 31P nuclei of 2,3 diphosphoglycerate (2,3-DPG) in living erythrocytes. The relaxation of water protons was also studied. Phosphorus relaxation is pH-dependent due to a modification of the binding of 2,3-DPG to hemoglobin. We compared the results obtained with normal and uremic erythrocytes. In uremic erythrocytes the 31P relaxation rates are increased, but the intraerythrocytic pH variation in uremic erythrocytes cannot itself explain this increase. A possible role of dialysable substances may explain the increased relaxation rate. PMID- 2912504 TI - Partial structure and hormonal regulation of rabbit liver inhibitor-1; distribution of inhibitor-1 and inhibitor-2 in rabbit and rat tissues. AB - Inhibitor-1 purified from rabbit liver could not be distinguished from the skeletal muscle protein by chromatographic, electrophoretic and immunological criteria. Amino acid sequences comprising 68% of rabbit liver inhibitor-1 were identical to the skeletal muscle protein indicating that they are products of a single gene. Total inhibitor-1 activity in heat-treated rabbit liver extracts was similar to that in skeletal muscle extracts, and the phosphorylation state of inhibitor-1 increased from 14% to 42% in rabbit liver in vivo after an intravenous injection of glucagon. Monospecific antibodies to rabbit skeletal muscle inhibitor-1 recognised a single major protein of identical electrophoretic mobility (26 kDa) in each rabbit tissue examined (skeletal muscle, liver, brain, heart, kidney, uterus and adipose). The antibodies also recognised a single major (30 kDa) protein in the same rat tissues, except liver. The results show that while there are interspecies differences in apparent molecular mass, inhibitor-1 is likely to be the same gene product in each mammalian tissue. Inhibitor-1 was not detected in rat liver, either by activity measurements or immunoblotting, irrespective of the age, sex or strain of the animals. Immunoblotting also failed to detect inhibitor-1 in mouse liver, although it was present in guinea pig, porcine and sheep liver. The absence of inhibitor-1 in rat liver indicates that phosphorylation of this protein cannot underlie the increased phosphorylation of hydroxymethylglutaryl-CoA reductase observed after stimulation by glucagon. Monospecific antibodies to rabbit skeletal muscle inhibitor-2 recognised a 31 kDa protein in each rabbit tissue, and a 33 kDa protein in all rat tissues including liver. The results suggest that inhibitor-2 is the same gene product in each mammalian tissue. PMID- 2912505 TI - Modulation of prostaglandin E2 catabolism and action by fuel substrates in rat hepatocytes. AB - The hepatic level of prostaglandins will reflect the balance between synthesis of prostaglandins and their rapid catabolism via beta-oxidation by hepatocytes. In the present study we examined the effect of physiological fuel substrates on the breakdown and action of prostaglandin E2 (PGE2) in isolated rat hepatocytes. Palmitic acid (0.32 mM), a long-chain fatty acid, inhibited the rate of PGE2 breakdown (10(-7) M) by approx. 80%. As the palmitic acid concentration was increased from 0 to 0.8 mM, the percentage of PGE2 remaining in the incubation 5 min following prostaglandin addition was raised from approx. 10% to over 98%. Octanoic acid (0.8 mM) also inhibited PGE2 catabolism, while butyric acid (0.8 mM) and pyruvic acid (2.5 mM) were without effect. The inhibition of glucagon stimulated glycogenolysis by PGE2 was increased in the presence of 0.6 mM palmitic acid, consistent with decreased PGE2 catabolism. These studies demonstrate that changes within the range of free fatty acid concentrations seen physiologically in vivo may dramatically alter PGE2 catabolism and, therefore, the effect of PGE2 to modulate hormonal action in the liver. PMID- 2912506 TI - Specificity determinants of maize casein kinase-IIB are related to but distinct from those of rat liver casein kinase-2. AB - The site specificity of maize seedling casein kinase-IIB, a type-2 casein kinase exhibiting an unusually low Mr, has been studied with the aid of model acidic peptide substrates for rat liver casein kinase-2. Like the animal enzyme, casein kinase-IIB also readily phosphorylates peptides SEEEEE, SEAEEE and SEEEAE, but not SEEAEE. Maize seedling casein kinase-IIB, however, is almost inactive toward peptides SAEEEE, SAEEEEE and SAAEEEEE which are good substrates for liver casein kinase-2. This indicates that casein kinase-IIB requires acidic residues not only at position +3, similar to rat liver casein kinase-2, but also at position +1, where the animal enzyme tolerates a neutral residue. This and other differences outlined in this report support the view that protein kinases of the same type from different sources may have significant differences in their substrate specificity. PMID- 2912507 TI - Effects of ATP reduction on the pattern of force development and myosin light chain phosphorylation in intact arterial smooth muscle. AB - The effect of reduction of ATP content on phosphorylation of the 20 kDa light chain of myosin (MLC) and force development in intact carotid arterial smooth muscle was investigated. With reduction of ATP to 23% of control by treatment with 2-deoxyglucose there was reduction in basal, in peak and 30 min MLC phosphorylation during contraction (P less than 0.001). The rate of force development was reduced, but maximal force was the same as control. By treatment with 50 microM iodoacetate, the resting ATP content was unchanged but fell to 22% after 30 min contraction. Basal MLC phosphorylation was the same as control, but peak (P less than 0.001) and 30 min phosphorylation were lower (P less than 0.005), even though the rate and magnitude of force development were greater. The results indicate that neither rate nor magnitude of force development correlate with MLC phosphorylation. Basal and initial MLC phosphorylation may play a cooperative role in contractile function. PMID- 2912508 TI - Triiodothyronine, thyroxine, and TSH response to dexamethasone in depressed patients and normal controls. AB - In view of recent investigations concerning alterations of thyroid function in depression, the pre- and postdexamethasone levels of T3, T4, and TSH of 14 patients during depression and after recovery were studied, in addition to those of 27 healthy controls. A reduction of T3 and TSH levels was shown to be dependent on the depressive state, with a tendency to lower T4 levels after recovery. Dexamethasone had a pronounced suppressive effect on TSH levels in healthy controls and in patients after recovery, but not during the depressive episode. These results point to an inadequate suppressibility of the hypothalamo pituitary-thyroid (HPT) axis to dexamethasone during depression. There are close interrelations between the hypothalamo-pituitary-adrenal (HPA) and the HPT axes that are possibly affected during depressive illness. PMID- 2912509 TI - Psychotic symptoms and the longitudinal course of senile dementia of the Alzheimer type. AB - Delusions, misidentifications and hallucinations occur frequently throughout the course of senile dementia of the Alzheimer type (SDAT). Rates of psychosis among subjects with moderate to severe SDAT range from 42% to 84% in our study group; at least half of persons with SDAT with no prior psychiatric history will display psychosis at some point during the course of dementia. Furthermore, psychotic symptoms are associated with accelerated cognitive deterioration, but not with increased mortality. PMID- 2912510 TI - Serum thyroxine change and clinical recovery in psychiatric inpatients. AB - Serum free thyroxine (FT4), total thyroxine (TT4), and Brief Psychiatric Rating Scale (BPRS) measurements were obtained following hospital admission and at 2 week intervals during hospitalization in 80 male psychiatric inpatients with a variety of major psychotic and affective disorders. A strong correlation between the range values for BPRS sum and for FT4 (p less than 0.005) and TT4 (p less than 0.001) levels indicated that change in overall symptom severity was linked to change in thyroxine levels during clinical recovery. We found the relationship not to be a simple one, but to require definition of criteria for three patient subgroups for each hormone, taking into account the initial absolute thyroxine level, as well as the direction and magnitude of hormonal change during recovery. The hormonally defined "good recovery" subgroup included patients with high initial thyroxine levels that then fell substantially, patients with low initial thyroxine levels that then rose substantially, and patients with initial thyroxine levels in the middle range that subsequently changed substantially. The hormonally defined "poor recovery" subgroup included those patients not meeting these criteria. The degree of clinical improvement in the hormonally defined good recovery group was significantly greater by almost twofold than the poor recovery group both for FT4 (p less than 0.04) and TT4 (p less than 0.02). These findings suggest that a "normalizing" principle underlies the relationship between clinical recovery and thyroxine levels and that both FT4 and TT4 levels within the normal range appear to have clinical significance in either reflecting or contributing to the course of a variety of psychiatric disorders and possibly having a role in pathogenesis. PMID- 2912511 TI - EEG sleep in young depressives: first and second night effects. AB - The sleep electroencephalogram (EEG) of young, drug-free, recurrently depressed outpatients was analyzed for 2 nights and was compared to age-matched controls using a variety of standard and computerized measures of sleep activity. On the first night, young depressives showed significantly greater difficulty in falling asleep and decreased sleep efficiency. Sleep architecture differences between the young depressives and controls were highlighted by increased percentages of Stage 2 sleep and major decreases in Stages 3 and 4 (delta wave) sleep among the depressives, as indicated by either period analyses or spectral analysis. The greatest differences in delta wave activity during night 1 were found in the first two (non-rapid eye movement (NREM) periods as measured by period analysis (NREM period 1, p less than 0.04; NREM period 2, p less than 0.001--average delta wave count) or by spectral analysis for the first 100 min of sleep (0.5-2.0 Hz). In contrast to the NREM sleep findings, various REM variables, including REM latency did not significantly distinguish the two subject groups for either night 1 or 2. Stepwise discriminant analysis demonstrated that night 1 sleep latency and delta wave counts during the second NREM period correctly classified 100% of all 16 individuals studied. The only differences between the young depressed patients and controls that remained on night 2 were significant reductions in slow-wave sleep as quantified by the computerized methods. Taken together, these findings suggest that the EEG response of young outpatients to the first night's stay in a sleep laboratory may be a useful tool for the diagnosis of depression in this age group. In addition, the use of computerized methods in this study point to an underlying deficit in delta sleep waveforms as being a prominent feature of the sleep of young depressed subjects. PMID- 2912512 TI - Biophysics Society: program and abstracts, thirty-third annual meeting. February 12-16, 1989, Cincinnati, Ohio. PMID- 2912513 TI - The place of the dream in psychotherapy. AB - The dream assumed an exceptional place in clinical practice beginning with Freud's extraordinary use of dream interpretation in his early presentations of psychoanalytic theory. Early students of analysis misconstrued this emphasis on the dream in theoretical exposition to apply to clinical practice as well. Eventually this difference was clarified, but there is still something exceptional about the dream in clinical practice that survives clarifications of this early misapprehension. The author reviews the historical issues, identifies the exceptional aspects of the dream in psychoanalytic practice, discusses some problems this phenomenon creates for the analyst, and describes several stereotypical attitudes toward the practice of dream interpretation. PMID- 2912514 TI - Acting out of separation conflicts in borderline pathology. An empirical case study. AB - The acting out of highly conflictual fantasies and feelings that develop around separations from significant others is a typical and challenging phenomenon for psychotherapists who treat borderline patients. The authors present a case study of a hospitalized 27-year-old woman with borderline pathology. Their account focuses on her experience and enactment of separation conflicts that emerged in psychotherapy (in dreams and transference) and in the inpatient milieu. To quantify and study the phenomena, the authors used an observational scheme and an acting-out scale. PMID- 2912515 TI - Adolescent gangs in the hospital. AB - Gang formation is common among adolescents, and the sociological dynamics of this phenomenon have been studied in depth. However, gang formation on mental health treatment units has not been extensively addressed. In this setting, gang members may disrupt treatment, threaten the safety of patients and staff, and leave the facility without receiving effective treatment. This impact motivated the authors to look beyond psychoanalytic and sociological models for an explanation of this phenomenon. After reviewing the literature and describing gang formation in a hospital, they apply a paradigm of moral development theory and suggest therapeutic interventions. PMID- 2912516 TI - The time limit in brief psychotherapy. AB - The time limit in psychoanalytically oriented brief psychotherapy has been construed as a motivation for the patient and the therapist to work more efficiently in therapy and as a stimulation of the patient's unconscious conflicts relating to separation and loss. The authors show that the time limit, in addition to the above functions, affects all focal conflicts in brief psychotherapy, whether or not they relate to separation issues. The time limit helps both patient and therapist to examine aspects of the patient's focal conflicts that tend to perpetuate symptoms or maladaptive patterns of behavior- that is, the primary gain of the symptom--and may therefore play a crucial role in the efficacy of brief psychotherapy. The authors also discuss implications for technique. PMID- 2912517 TI - Rorschach correlates of treatment difficulty in a long-term psychiatric hospital. AB - There are no studies of the use of the Rorschach test to predict possible treatment difficulties with hospitalized psychiatric patients. To explore this area, the authors assessed the Rorschach protocols of 114 patients using 19 example-anchored rating scales. They conducted a factor analysis of the scales and correlated the resulting factor scores with the extent and type of treatment difficulty. Although there were few significant findings, the Rorschach factors of Dysphoric Affect, Mirroring, and Depreciation may warrant further investigation of their predictive value for treatment difficulty. Rorschach measures of severity of psychological disturbance, inability to represent aggression in ideation, and depreciation may help treaters anticipate types of treatment difficulty. PMID- 2912518 TI - Types of institutional transference. AB - Institutional transference is a common clinical phenomenon. The patients in whom it was originally described represent but one subset of this entity. The author describes four types of patients who manifest institutional transference and demonstrates how and why it develops. He notes that institutional transference does not preclude transference and emotional attachment to an individual clinician, and emphasizes that understanding which type of institutional transference appears in a patient aids the diagnosis and treatment of that patient. PMID- 2912519 TI - Low-dose cytosine arabinoside in acute non-lymphoblastic leukemia. AB - Eighteen previously untreated patients with acute non-lymphoblastic leukemia (ANLL) were treated with cytosine arabinoside (Ara-C) in low doses (10 mg/m2 every 12 hours) subcutaneously for 3 weeks. Complete remission (CR) was achieved in four patients (22.2%), and myelosuppression was observed in nearly all of them. Thrombocytopenia (20 X 10(3)/microliters) was pronounced in the third week of treatment and six patients (33.3%) needed platelet support. Contrary to earlier claims, our experience suggests that treatment with low-dose Ara-C is associated with significant cytopenias. Ara-C does not obviate the need for intensive supportive care and CR rates are no longer better. Low-dose Ara-C does not seem to be a choice in previously untreated ANLL patients who otherwise have a high probability of achieving a CR with standard multidrug chemotherapy protocols. PMID- 2912521 TI - High-dose cisplatin for locally advanced or metastatic head and neck cancer. A phase II pilot study. AB - High-dose cisplatin (40 mg/m2 every day X5) was administered to 14 patients (11 men, three women) with locally advanced or metastatic head and neck cancer not curable by surgery or refractory to previous chemotherapy and/or radiation therapy. All 14 patients were evaluable for toxicity; one patient was inevaluable for response due to early death. A total of 24 courses of therapy were administered. The dose-limiting toxicity was myelosuppression with 73% of patients experiencing Grade III or IV neutropenia. Grade II or above thrombocytopenia occurred in 30% of the patients. Renal and neurologic toxicity was minimal. Two patients experienced laryngeal edema from vigorous hydration with one of them requiring a tracheostomy for respiratory compromise. Partial responses were seen in six patients (46%). Two of the six patients had received previous treatment with standard dose cisplatin. Two patients achieved long-term responses (54+, 44+ months, respectively). Both of these patients were previously untreated, inoperable (T4N3M0, T3N1M0), and subsequently received radiation therapy after two cycles of chemotherapy. Median duration of response in the remaining responders was 3 months (range, 3-10 months). High-dose cisplatin may benefit selected patients with inoperable, advanced head and neck tumors. However, further randomized trials need to be conducted before firm conclusions can be established. PMID- 2912520 TI - Low-dose continuous infusion 5-fluorouracil. Evaluation in advanced breast carcinoma. AB - Low-dose continuous infusion 5-fluorouracil (LDCI-FU) was administered to 28 women with advanced breast carcinoma. Daily doses ranged from 175 to 250 mg/m2. The LDCI-FU was delivered continuously until the appearance of toxicity and was reinstituted at a 20% dose reduction after toxicity completely resolved. Patients with a median age of 56 years and a median performance status of 60% (Karnofsky) had been previously treated with combination chemotherapy. Complete responses were observed in two patients with soft tissue metastases. Thirteen patients experienced partial responses with a median duration of response of 4+ months. Partial responses were predominantly observed in soft tissue disease; however, five patients with visceral metastases experienced partial tumor regression. Median survival for the study group was 4+ months. Hormonal receptor status did not predict response to LDCI-FU. Toxicities included stomatitis, ten patients; hand-foot syndrome, eight patients; mild leukopenia, two patients; moderate thrombocytopenia, two patients; diarrhea, three patients; ataxia, three patients. Catheter-related toxicities of sepsis and/or thrombosis occurred in six patients. Because of the demonstrated activity in previously treated patients (53% response rate), LDCI-FU should be investigated in combination chemotherapy regimens in untreated breast cancer patients. PMID- 2912522 TI - Jaundice and intrahepatic cholestasis following high-dose megestrol acetate for breast cancer. AB - High-dose megestrol acetate, a synthetic progestin, has been advocated recently in treating patients with metastatic breast carcinoma; no significant increase in adverse effects has been reported. This report describes a patient with jaundice and intrahepatic cholestasis after high-dose megestrol acetate therapy. This cholestatic lesion may have a pathogenesis similar to that observed with estrogens and oral contraceptives. PMID- 2912523 TI - Prognostic factors for relapse after complete response in patients with metastatic germ cell tumors. AB - Among 216 patients with metastatic germ cell tumors who achieved a complete response (CR) to cisplatin-based chemotherapy (CT), 38 have experienced a relapse. Prognostic factors for time to relapse from time of response were considered using the Cox proportional hazards model. Compared with patients who responded to CT and did not require surgery and patients whose surgery showed only either necrotic debris or mature teratoma, those who required surgery for residual tumor after CT were at much higher risk for relapse, although their residual tumor was totally resected. Of the 19 patients who required this surgery, eight have experienced a relapse. Other prognostic factors for relapse included lactate dehydrogenase (LDH) and human chorionic gonadatropin (hCG) at the time of initial CT. Although those who require surgery for residual tumor after CT receive additional CT, there is still a high risk of relapse. PMID- 2912524 TI - High concentrations of chromium in lung tissue from lung cancer patients. AB - The pulmonary chromium content was determined by plasma atomic emission spectrometer (DCP-AES) from 53 lung cancer and 43 control patients, and compared with smoking habits, severity of emphysema and occupational history. The chromium content from the lung cancer patients was higher than that from the smoking (P less than 0.025) or nonsmoking control patients (6.4 +/- 4.3, 4.0 +/- 4.0, and 2.2 +/- 0.6 microgram/g dry weight, respectively). A positive correlation between the pulmonary chromium and smoking time (P less than 0.025) and the severity of emphysema (P less than 0.001) was found in the control but not in the cancer patients. The difference in the pulmonary chromium content was greatest between those lung cancer and control patients who were light smokers or had mild emphysema. This group of lung cancer patients included subjects with occupational exposure to chromium. The possibility of occupational cancer should be considered especially with light smokers. The grade of emphysema and metals such as chromium accumulating from tobacco could serve as objective indicators of smoking. PMID- 2912525 TI - Nucleolar organizer regions in Spitz nevi and malignant melanomas. AB - Nucleolar organizer regions (NOR) are loops of DNA that transcribe ribosomal RNA; they can be easily identified in formalin fixed paraffin embedded tissue using a silver (Ag) method. It has been suggested that the number of AgNOR per cell can differentiate between benign and malignant melanocytic lesions of skin. We have studied 29 Spitz nevi (SN) and 39 invasive malignant melanomas (MM) by the same silver method. SN showed between 1.0 and 1.6 AgNOR per cell with a mean of 1.2. MM counts ranged from 1.2 to 4.2 with a mean of 2.0. It is concluded that the AgNOR method cannot reliably differentiate SN from MM; however, a count of more than 2.0 AgNOR per cell would favor a diagnosis of MM rather than SN. PMID- 2912526 TI - Characterization of pyruvate kinase from human rhabdomyosarcoma in relation to immunohistochemical and morphological criteria. AB - We have compared the pyruvate kinase (PK) isoenzyme pattern of three rhabdomyosarcomas with foetal skeletal muscle tissue of 19 and 23 weeks of gestation, together with adult muscle in relation to immunohistochemical and morphological criteria. In foetal tissue of 19 weeks of gestation a focal immunopositivity for desmin and myoglobin was observed, whereas in tissue of 23 weeks an overall positivity for these proteins was present. Two of the three neoplasms were poorly differentiated and of the alveolar subtype. They were desmin immunoreactive. Some large spindle-shaped cells expressed myoglobin. The third one was more differentiated in microscopic characteristics and all cells showed immunoreactivity for desmin and myoglobin. In the foetal tissues five forms of pyruvate kinase isoenzymes were present with K2M2 as the predominant form. In adult muscle tissue only M4 was present. The tumors were characterized by a profound shift to the K-type, whereas the M4-type was not expressed at all. A difference in isoenzyme composition of pyruvate kinase was found between the morphologically less differentiated tumors and the more differentiated tumor; in the latter more M-subunits were expressed. PMID- 2912527 TI - Prognostic relevance of urinary neopterin in non-Hodgkin's lymphomas. AB - Neopterin excretion levels were assessed in 66 consecutive patients affected by non-Hodgkin's lymphomas (NHL). The logarithm of the mean value of the whole series was 2.71 (log [mumol neopterin/mol creatinine]), significantly higher (P less than 0.001) than the control value (2.12). Fifty-six of 66 patients had a raised excretion of neopterin in amounts statistically related to the stage of disease. The mean value (2.51) of patients in Stages I-II was lower than the mean value (2.86) of patients in Stage III-IV (P less than 0.001). The 2-year probability of survival was 64% for patients in Stages I-II and 34% for patients in Stages III-IV. However, patients with lower neopterin excretion (less than 2.65) fared better than patients with higher neopterin excretion, regardless of the stage. Longitudinal analysis showed a trend toward a correlation between response to therapy and neopterin excretion. In NHL, the raised neopterin excretion appears to be a consequence of activation of the host immune system rather than a product of the malignant cells. But this excessive activation of the monocytes-macrophages, as reflected by urinary neopterin levels, is not accompanied by a better outcome. In conclusion, although neopterin cannot be considered a typical tumor marker, nevertheless it is an useful prognostic marker in NHL. PMID- 2912528 TI - S-100 protein-positive dendritic cells in colorectal adenocarcinomas. Distribution and relation to the clinical prognosis. AB - Dendritic cells (DC) in 121 colorectal adenocarcinomas were investigated immunohistochemically, using anti-S-100 protein antibody. S-100(+)DC were recognized among the malignant cells and/or around the tumor and differed in distribution either from lysozyme-positive macrophages or from neuron-specific enolase-positive neural tissue. Patients with many S-100(+)DC (more than 30 cells per 10 high-power fields) in the tumor survived longer than did those with few such cells (less than 30 cells), most often with no metastases (P less than 0.001). The grade of S-100(+)DC infiltration was related to both density of lymphocytic infiltration in the primary tumor and the degree of paracortical hyperplasia in the regional lymph nodes (P less than 0.05). Dendritic cells, therefore, as antigen-presenting cells, conceivably mediate cell immunity in a tumor with lymphoid infiltration and in the regional lymph nodes. The number of S 100(+) DC in the primary colorectal carcinomas represents one aspect of such a series of antitumor immunoreaction, in vivo. PMID- 2912529 TI - Giant-celled glioblastoma of brain. A clinico-pathological and radiological study of ten cases (including immunohistochemistry and ultrastructure). AB - Giant-celled glioblastoma multiforme is characterized by bizarre multinucleated giant cells with abundant eosinophilic cytoplasm, paucity of vascular endothelial proliferation, and increased reticulin fibers. It is considered by Rubinstein to be a variant of glioblastoma multiforme and by Zulch to be of mesenchymal origin. We studied retrospectively ten cases of giant-celled glioblastoma to correlate clinical and pathological features including immunohistochemistry and ultrastructure, radiology and survival time. Seven men and three women ranging in age from 23-75 years had variable clinical presentations and well defined lesions on computed tomography (eight patients). Well-defined at surgery, the tumor was located in temporal (six patients), frontal (three patients), and parieto occipital (one patient) lobes. Besides characteristic histology, glial-fibrillary acidic protein was positive in all, along with intracytoplasmic fibrils on electron microscopy. Three patients died within 3 days of surgery. Of the surviving seven treated with radiation and/or chemotherapy, three had a survival time of more than 36 months and four less than 15 months. Our study identifies this tumor to be of astrocytic lineage, with temporal lobe predilection, and overall a longer survival rate than glioblastoma multiforme. PMID- 2912530 TI - An index for estimating the probability of lymph node metastasis in rectal cancers. Lymph node metastasis and the histopathology of actively invasive regions of cancer. AB - We examined resected specimens from 40 cases of advanced rectal cancer to determine the extent of microtubular cancer nests and undifferentiated cancer cells (budding). We investigated the relationship between this budding and lymphatic invasion (ly), venous invasion (v), and lymph node metastasis (n), respectively. Moreover, we examined the relationship between ly, budding, and n in the preoperative biopsy specimens of 112 patients, including those of the 40 cases mentioned above. The degree of budding, which was abundant in the actively invasive region, showed a strong correlation with the degree of ly and the existence of n in the resected specimens. Also, budding was recognized in a relatively large portion of the biopsy specimens (52 of 112 [46.4%]) and lymph node metastasis was found in 41 of 52 specimens (78.8%). In 57 specimens, neither ly nor budding was found, and 16 of these specimens (28.1%) had positive lymph nodes. These results implied that the degree of budding in the actively invasive region can be a great help in predicting the presence of n. The presence or absence of budding in preoperative biopsy specimens also can be an important factor (along with the degree of differentiation and ly) in estimating the probability of n. PMID- 2912531 TI - Clinical and histopathologic characteristics of early lesions of subungual malignant melanoma. AB - Twenty-one Japanese cases of subungual malignant melanoma were investigated clinically and histologically. In the majority of the cases, the initial sign of the disease was confirmed to be melanonychia striata. Five cases of Clark's Level I melanoma were found in the series. Melanonychia striata had appeared as the initial sign in these five cases. Melanonychia striata is frequently observed in persons who are not white and is attributed to various local and systemic causes. Detailed clinical analysis of the five cases of early subungual melanoma showed that melanonychia striata with the following characteristics may increase the risk of early subungual melanoma developing: it is noticed during adulthood, it is broader than 6 mm, it is brownish with variegated shades or homogenously black, and it is accompanied by periungual pigmentation (Hutchinson's sign). Detection of early lesions of subungual melanoma is beneficial not only for the improvement of prognosis, but also for the preservation of the affected phalanx. PMID- 2912532 TI - Muscle cramps in cancer patients. AB - We prospectively evaluated 50 cancer patients with new complaints of muscle cramps. Neurologic examination and laboratory evaluation identified disorders related to neural, muscular, or biochemical abnormalities in 41 (82%) patients. Abnormalities were confined mainly to the peripheral nervous system and included peripheral neuropathy in 22 patients, root and plexus pathology in 17 patients (six with leptomeningeal metastases), and polymyositis in two patients. Hypomagnesemia accounted for muscle cramps in only one patient. Identifiable causes of muscle cramps were related mostly either to metastatic or nonmetastatic complications of the underlying malignancy (14 patients) or to complications of its treatment (21 patients). Cramps, or rather complaints of cramps, were the presenting symptom of recognizable and previously unsuspected neurologic dysfunction in 64% (27 of 42) of the identified causes. Therefore, we conclude that muscle cramps in cancer patients may not be a benign complaint and that they usually mark the presence of an identifiable neurologic disorder. The use of simple clinical and laboratory measures is rewarding in the evaluation of these patients and leads to diagnosis in the majority of them. PMID- 2912533 TI - Metoclopramide versus metoclopramide and lorazepam. Superiority of combined therapy in the control of cisplatin-induced emesis. AB - Sixty-four patients treated with cisplatin-containing regimens were entered into a randomized, double-blinded study examining the antiemetic efficacy of metoclopramide with and without lorazepam for control of cisplatin-induced emesis. Metoclopramide was administered to all patients at 2 mg/kg, intravenously, 30 minutes before chemotherapy and 1.5, 3.5, and 5.5 hours posttreatment. Patients randomized to receive combined antiemetic therapy were administered lorazepam at 2 mg/m2 (maximum, 4 mg dose) intravenously, 30 minutes before chemotherapy. Those patients not receiving lorazepam were given normal saline placebo. Degree of nausea and number of vomiting episodes were recorded on a data flow sheet with a visual analogue scale. Drug toxicities were evaluated before each administered dose. Patients receiving both metoclopramide and lorazepam experienced significantly less vomiting episodes (P less than 0.05) and nausea (P less than 0.01) when compared to patients given metoclopramide alone. Forty-four percent of those receiving the combined therapy reported no nausea or vomiting episodes compared to only 22% receiving metoclopramide alone. Sedation was significantly more common in patients receiving lorazepam (88%) as opposed to patients receiving only metoclopramide (43%), P less than 0.01. Amnesia was seen in 25% receiving lorazepam. No significant difference in diarrhea, dystonia, or disinhibition was observed between the two arms. The authors conclude that the combination of lorazepam and metoclopramide was superior to metoclopramide alone in the prevention of cisplatin-induced nausea and vomiting, with sedation and amnesia more commonly observed in the combined regimen. PMID- 2912534 TI - Expanded role for fine needle aspiration of the prostate. A study of 335 specimens. AB - In 279 patients, 335 cytologic samples were obtained from the prostate and correlated with histology obtained by core needle biopsy in 189 cases. Approximately 6% of the cytologic specimens were inadequate for diagnosis. The unconfirmed positive rate for malignancy was 1.6%, the false-negative rate was 27.9%, and the accuracy rate was 89.6%. Granulomatous inflammation was diagnosed in 19 cases, and three cases of tumors other than acinar carcinoma of the prostate were encountered. Based on our experience, cytologic criteria for the diagnosis of prostatic adenocarcinoma are described. PMID- 2912535 TI - Is there an increased incidence of adenomatous polyps in breast cancer patients? AB - Using flexible proctosigmoidoscopy, the incidence of adenomatous polyps was studied in 161 patients previously operated on for breast cancer and also in 147 hospitalized controls not presenting with colorectal symptoms. The acceptance and tolerance of the examination were good in both populations. The mean age and length of the colons explored were not statistically different for the two groups. The incidence of adenomas was high in the breast cancer group (14.2%) in comparison to the control group (4.7%) (P less than 0.01). This strong incidence especially concerned very small polyps with a diameter smaller than 3 mm. There were also two polyps with superficial carcinomas in the breast cancer group. Breast cancer does indeed seem to represent a condition with a high risk of colorectal adenomas. Our results prompt us to propose the adoption of systematic screening measures and a surveillance schedule as soon as the breast cancer is found. PMID- 2912537 TI - [The Nurses' Association of New Brunswick and AIDS]. PMID- 2912536 TI - Side effects and emotional distress during cancer chemotherapy. AB - Chemotherapy side effects, patient distress, and patient-practitioner communication were evaluated in an inception sample of 238 patients with breast cancer or malignant lymphoma. Participants were interviewed at five points during their first six cycles of therapy, and a subsample kept brief daily symptom diaries. Nausea, hair loss, and tiredness were each experienced by more than 80% of patients. By cycle 6, 46% of patients had thoughts about quitting therapy, but only a few had told medical staff. Patients' ratings of the objective difficulty of treatment increased over time, varied by treatment regimen, and were predicted by the experience of side effects, with the number of different side effects serving as the best predictor. In contrast, emotional distress was less sensitive to the directly assessable characteristics of treatment. Communication between patient and practitioner was found to be inadequate in a number of respects (i.e., patients did not fully anticipate the toxicities of treatment and did not report their concerns to medical staff). Communication may be impeded by inaccuracies in a patient's recall of treatment difficulties and by a patient's inability or unwillingness to attend to all presented information. More frequent opportunities for patient-practitioner discussion are necessary. PMID- 2912538 TI - I have AIDS. PMID- 2912539 TI - Children and tobacco. PMID- 2912540 TI - Nurses' smoking behavior. PMID- 2912541 TI - Nursing up North. PMID- 2912542 TI - Neonatal heel puncture. PMID- 2912543 TI - [Care of persons with cognitive deficiencies]. AB - Care of those with cognitive deficits. Even a decade ago, articles on aging and those with cognitive deficits attracted relatively little attention. Now, educators, health care professionals and researchers alike consider the aged and maintenance of their autonomy to be priorities. Yet in spite of the good intentions of these groups, there will be no significant changes in care of the elderly and those with cognitive deficits without the cooperation and commitment of health care administrators, say these authors. As such, they raise questions about the way health institutions and more precisely care services and units are administered. The article also examines how history affects the organization of care--in particular, daily care. It is written in administrative terminology. PMID- 2912544 TI - [Prevention, why resist it?]. AB - Prevention, why resist it? Based on a 1988 speech the author gave to infection control professionals in Montreal, this article draws a parallel between individuals' resistance to change and their reaction to infection control programs. Gladly, many of the same well-honed techniques that help change along can be applied to infection control efforts, he says. Analyzing the implementation of an infection control program for AIDS in a health center, the author emphasizes do's and don'ts and explores appropriate and inappropriate approaches to leadership, conflict prevention and problem solving. To sell your program, he says, you must also sell yourself; you must be convincing and credible. PMID- 2912545 TI - Effects of human bone marrow stroma on the growth of human tumor cells. AB - As some tumors metastasize frequently to marrow we modified the clonogenic assay for human tumor cell growth by culturing tumor cells in the presence of human bone marrow stromal cells. In a bilayer soft agar assay, human tumor cells which had been passaged in nude mice were plated in the agar overlayer on an underlayer containing a suspension of trypsinized human bone marrow stromal cells. These marrow stromal cells stimulated the growth of tumor cells in a dose-dependent fashion, with a growth peak at a stromal cell density of 5-10 x 10(5)/ml. The maximal stimulation of tumour cell growth was 13-fold. We evaluated clonal growth of six separate tumors of five different histological types (small and large cell bronchogenic carcinoma; mammary carcinoma; malignant melanoma; pleural mesothelioma) and demonstrated that in 9 of 11 experiments tumor cell colonies formed in the absence of stromal cells, but colony growth was markedly stimulated by stromal cells in every case. Stromal stimulation persisted after irradiation of the stromal cells with 10 Gy. Growth of five fresh human tumor samples was similarly stimulated by the presence of human bone marrow stromal cells. Tumor cell colonies were characterized morphologically by Pappenheim stain and immunologically for surface antigens by peroxidase-antiperoxidase immunostaining utilizing monoclonal antibodies (carcinoembryonic antigen 26/3/13 and 26/5/1, EMA, HEA125, Sam 2 and Sam 10) which detected epithelial cell antigens. Colonies consisted of cytologically malignant cells which expressed epithelial cell antigens. Thus, the tumor cell origin of colonies from mammary carcinoma and bronchogenic small cell, large cell, and adenocarcinoma was proven. This tumor stem cell assay permits further analyses of human tumor cell biology and may be useful for testing drug sensitivity. PMID- 2912546 TI - Resistance to neoplastic transformation induced by nonterminal differentiation. AB - Cell clones derived from undifferentiated 3T3 T mesenchymal stem cells show a low rate of spontaneous transformation but can be efficiently transformed by a variety of carcinogens. In contrast, it is now reported that cell clones derived from nonterminally differentiated 3T3 T stem cells are highly resistant to neoplastic transformation induced by physical and chemical carcinogens. Differentiation-induced resistance to neoplastic transformation is evident in both in vitro and in vivo transformation assays and can be stably expressed for greater than 50 population doublings. These results establish that resistance to neoplastic transformation can be regulated in mammalian stem cells by the process of nonterminal differentiation. PMID- 2912547 TI - Modulation of growth and epidermal growth factor receptor activity by retinoic acid in human glioma cells. AB - The growth-inhibitory activity of beta-all-trans-retinoic acid (RA) was examined on seven cultured human gliomas and cells derived from one normal brain. Response in monolayer cultures was heterogenous: three cell lines were completely resistant whereas five cell lines were growth inhibited with 50% inhibitory dose ranging from greater than 10(-5) to 1 x 10(-8) M. Two glioma cell lines capable of forming colonies in soft agar exhibited dose-dependent sensitivity to RA induced growth inhibition, whereas another cell line was not affected by RA under either growth condition. Cell cycle analysis of the glial-derived cells has shown that the RA-sensitive cells accumulated in the G0-G1 phase. The cell surface expression of epidermal growth factor (EGF) receptors displayed by the various cells was either slightly increased or not affected by RA. In addition, the affinity of binding was slightly decreased in some sensitive cells. The activity of EGF receptor as assessed by immunocomplex-kinase assays revealed a dose dependent decrease in autophosphorylation activity that appeared to correlate with the growth inhibition. The decrease in phosphokinase activity represented a dose-dependent inhibition of phosphorylation on tyrosine residues on EGF receptor as well as several other substrates. Furthermore, the autophosphorylation of either RA-treated or untreated EGF receptors occurred on similar amino acid residues. These results demonstrate that RA exhibits a heterogeneous growth inhibitory activity against human glioma cells and suggest that the effects of RA may be mediated, at least in part, by modulation of EGF receptor phosphotyrosine kinase activity. PMID- 2912548 TI - Study of the ability of phenacetin, acetaminophen, and aspirin to induce cytotoxicity, mutation, and morphological transformation in C3H/10T1/2 clone 8 mouse embryo cells. AB - Use of the analgesic compounds acetylsalicylic acid (aspirin), phenacetin, and acetaminophen has been correlated with increased risk of renal cancer in humans. Hence, we studied these compounds for ability to induce cytotoxicity, mutation to ouabain resistance, and morphological transformation in cultured C3H/10T1/2 clone 8 (10T1/2) mouse embryo cells. All three compounds were cytotoxic from 0.5-mg/ml to 2-mg/ml concentrations as evidenced by decreased plating efficiency. None of the compounds induced detectable base substitution mutations to ouabain resistance even at cytotoxic concentrations. Aspirin did not induce morphological transformation. Both phenacetin and acetaminophen induced low but concentration dependent numbers of atypical, weak type II morphologically transformed foci; at equimolar concentrations, phenacetin was 1.1- to 3.0-fold more active in inducing these foci. Neither phenacetin nor acetaminophen was cotransforming with 3 methylcholanthrene, and neither compound promoted cell transformation when added to 3-methylcholanthrene-initiated 10T1/2 cells. The focus-inducing potency of both compounds was increased by addition of an Arochlor-induced hamster liver S9 fraction as an exogenous metabolizing system. However, seven putative metabolites of phenacetin and acetaminophen that were tested--N-hydroxyphenacetin, p phenetidine, p-aminophenol, p-nitrosophenol, benzoquinone, acetamide, and N acetyl-p-benzoquinoneimine--were inactive in transformation assays at the concentrations reducing plating efficiency of treated cells to 50% of the plating efficiency of nontreated (control) cells. Several acetaminophen- and phenacetin induced foci were cloned, expanded into cell lines, and characterized. These cell lines stably formed type II foci when maintained at confluence for 2 to 4 wk in reconstruction experiments with nontransformed 10T1/2 cells; however, they did not exhibit significantly increased saturation density compared to 10T1/2 cells, and they did not grow in soft agarose. These results suggest that metabolic intermediates of high concentrations of phenacetin and acetaminophen induce a low frequency of nonneoplastic morphological transformation of 10T1/2 mouse embryo cells. PMID- 2912549 TI - Analgesics, cigarette smoking, and other risk factors for cancer of the renal pelvis and ureter. AB - Results from a population-based case-control study of cancer of the renal pelvis and ureter are reported. Telephone interviews were conducted with 187 residents of Los Angeles County diagnosed with cancer of the renal pelvis and ureter over a 4-year period ending December 31, 1982, and with individually sex-, age- and race matched neighborhood controls. The major risk factor identified for cancer of the renal pelvis and ureter was cigarette smoking. Subjects who smoked more than 25 years had a relative risk of 4.5 of developing these tumors, compared to nonsmokers (P less than 0.0001). Heavy use of over-the-counter analgesics was also associated with a significant increase in risk; it appears that an elevated risk was conveyed by all the major active constituents of those compounds currently marketed in the United States, aspirin, caffeine, and acetaminophen. Persons who had used these drugs for 30 consecutive days at any time in their life preceding diagnosis had twice the risk of developing cancer of the renal pelvis or ureter compared to persons not reporting such use (P less than 0.01). Heavy coffee drinkers (greater than or equal to 7 cups/day) had a 1.8-fold increase in risk compared to nondrinkers. Although risk tended to increase with increasing consumption, this result was not statistically significant. The risk associated with heavy coffee consumption was reduced to 1.3 after adjusting for smoking. Nine cases compared to no controls reported a first degree relative with kidney cancer. A history of kidney stones was associated with an increased risk of cancer of the ureter (relative risk = 2.5) that was not, however, statistically significant. PMID- 2912550 TI - Coffee consumption and digestive tract cancers. AB - The relationship between coffee drinking and the risk of digestive tract neoplasms was analyzed in a case-control study of 50 cases of cancer of the mouth or pharynx, 209 of the esophagus, 397 of the stomach, 455 of the colon, 295 of the rectum, 151 of the liver, 214 of the pancreas, and 1944 control subjects admitted for acute, non-digestive tract disorders. There was no significant or consistent association between coffee and cancers of the mouth or pharynx, esophagus, stomach, liver, or pancreas. In particular, for pancreatic cancer, the multivariate relative risks for the intermediate and upper tertiles were 1.05 and 1.01, respectively. There were significant inverse trends in risk with measures of coffee consumption for colon and rectal cancers, the multivariate relative risks according to tertiles of coffee consumption being 0.86 and 0.64 for colon and 0.97 and 0.66 for rectum. This apparent protection is in agreement with some (but not all) previous epidemiological evidence and finds a possible biological interpretation in terms of interference on bile secretion, causing reduced bile acid and neutral sterol concentrations in the bowel. In conclusion, the results of this study, the major interest of which lies in the opportunity of drawing up an overall pattern of risk for various digestive neoplasms, offer further reassurance as regards the effects of coffee on digestive tract carcinogenesis. PMID- 2912551 TI - Classification of lung cancer patients and controls by chromatography of modified nucleosides in serum. AB - A wide spectrum of modified nucleosides has been quantified by high-performance liquid chromatography in serum of 49 male lung cancer patients, 35 patients with other cancers, and 48 patients hospitalized for nonneoplastic diseases. Data for 29 modified nucleoside peaks were normalized to an internal standard and analyzed by discriminant analysis and stepwise discriminant analysis. A model based on peaks selected by a stepwise discriminant procedure correctly classified 79% of the cancer and 75% of the noncancer subjects. It also demonstrated 84% sensitivity and 79% specificity when comparing lung cancer to noncancer subjects, and 80% sensitivity and 55% specificity in comparing lung cancer to other cancers. The nucleoside peaks having the greatest influence on the models varied dependent on the subgroups compared, confirming the importance of quantifying a wide array of nucleosides. These data support and expand previous studies which reported the utility of measuring modified nucleoside levels in serum and show that precise measurement of an array of 29 modified nucleosides in serum by high performance liquid chromatography with UV scanning with subsequent data modeling may provide a clinically useful approach to patient classification in diagnosis and subsequent therapeutic monitoring. PMID- 2912552 TI - Enhancement of experimental gastric carcinogenesis induced in spontaneously hypertensive rats by N-methyl-N'-nitro-N-nitrosoguanidine. AB - The incidence, number, and histological types of gastric cancers induced by N methyl-N'-nitro-N-nitrosoguanidine and the tissue norepinephrine concentration of the gastric wall were investigated in spontaneously hypertensive rats and in control Wistar Kyoto rats and Wistar rats. All rats were given drinking water containing 25 micrograms/ml of N-methyl-N'-nitro-N-nitrosoguanidine for 25 weeks. During Week 52, the incidence and number per rat of gastric cancers were significantly greater in spontaneously hypertensive rats than in Wistar Kyoto and Wistar rats. All tumors induced in the glandular stomach were adenocarcinomas, but no significant difference was found in the histological types of adenocarcinoma in the three strains of rats. At Weeks 15, 30, and 52, norepinephrine concentrations in the fundic and antral portion of the gastric walls and labeling indices in the antral and fundic mucosa were significantly higher in spontaneously hypertensive rats than in Wistar Kyoto and/or Wistar rats. These findings indicate that increased sympathetic nervous system activity enhances the development of gastric cancers, but immunological dysfunction in spontaneously hypertensive rats may contribute to the increased susceptibility to gastric cancer. PMID- 2912553 TI - Purification and characterization of cytochrome P-450 induced by benz(a)anthracene in mouse skin microsomes. AB - Topical application of benz(a)anthracene to mouse skin elicited a 2-fold increase in cytochrome P-450 content, with accompanying increases in monooxygenase activities such as benzo(a)pyrene hydroxylation, 7-ethoxycoumarin O-deethylation, and acetanilide 4-hydroxylation, in the microsomes. A major form of cytochrome P 450 was purified from skin microsomes of mice treated with polycyclic aromatic hydrocarbon. A specific content of 1.95 nmol/mg of protein, which corresponded to 48-fold purification from the microsomes, was observed. The purified protein produced a single major band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis having a molecular weight of 55,000. Using Western blotting, the band immunochemically cross-reacted with antibody which had been raised against rat liver cytochrome P-450MC-1. The purified preparation efficiently catalyzed benzo(a)pyrene hydroxylation and 7-ethoxycoumarin O-deethylation when reconstituted with NADPH-cytochrome P-450 reductase. These activities were inhibited by 7,8-benzoflavone as well as anti-cytochrome P-450MC-1 antibody, but not by P-450PB-1 antibody. The results indicate that, in mouse skin microsomes, a cytochrome P-450 induced by benz(a)anthracene is enzymatically and immunochemically similar to rat liver cytochrome P-450MC-1. It is suggested that this enzyme plays an important role in the activation of carcinogenic polycyclic aromatic hydrocarbons. PMID- 2912554 TI - Examination of urokinase protein/transcript levels and their relationship with laminin degradation in cultured colon carcinoma. AB - Conditioned medium derived from the colon cancer cell lines was ineffective in solubilizing immobilized radiolabeled laminin. However, substantial degradation was observed in the presence of plasminogen and could be largely blocked by preincubation with polyclonal anti-urokinase antibody. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of the solubilized products generated either by the conditioned medium or by authentic urokinase supplemented with plasminogen yielded identical results. Analysis of the spent medium for urokinase by an enzyme-linked immunosorbent assay method revealed a similar profile to that achieved with the laminin degradation assays for the six cell lines tested. However, Northern analysis of urokinase-specific mRNA indicated that protein levels could not be entirely predicted by steady-state levels of the transcript. In a previous study, undifferentiated colon cancer cell lines expressed larger amounts of the plasminogen activator into the conditioned medium compared with their well-differentiated counterparts. However, these earlier studies were performed using cells grown in defined medium which lacked epidermal growth factor (EGF). EGF has been reported to affect plasminogen activator levels. Consequently, to investigate the role of EGF in the modulation of urokinase protein/activity, cell types representative of well- and poorly differentiated colon cancer were examined for their sensitivity of expression to this growth factor. In the absence of EGF, primitive cell types secreted, on average, 5 times more urokinase than their well-differentiated counterparts. In response to EGF, however, well-differentiated cell lines exhibited 4- to 6-fold increases in these parameters while the primitive cell lines were refractory to the peptide. Consequently, the differences in urokinase protein expressed by the well- and poorly differentiated groups of cells were abolished by the presence of EGF. The expression of a well-differentiated phenotype by colon cancer cell types in vivo probably depends to some extent on laminin within a basement membrane. The data presented herein are consistent with the idea that depletion of this glycoprotein from a basement membrane by urokinase-dependent mechanisms may contribute to the undifferentiated phenotype seen with many of these malignancies. PMID- 2912555 TI - Excretion and metabolism of mitoxantrone in rabbits. AB - The hepatic clearance of mitoxantrone was evaluated in rabbits using both bile duct cannulated animals and freshly isolated hepatocytes in suspension or in primary culture. Mitoxantrone metabolic behavior was assessed by high-performance liquid chromatography using a method which specifically resolved mitoxantrone from its mono- and dicarboxylic acid derivatives. Excretion of mitoxantrone in bile and urine was studied over a 6-h period of observation following i.v. bolus injection of 0.04, 0.20, and 1.0 mg [14C]mitoxantrone/kg. Bile route represented the main excretion pathway for mitoxantrone and its metabolites--mainly the monocarboxylic acid derivative. Biliary excretion was very rapid (maximum biliary concentration achieved 9 to 18 min following drug administration) and amounted to 29.5 +/- 9.3%, 27.6 +/- 7.9%, and 28.3 +/- 3.8% of administered drug, respectively. Urinary excretion amounted to 7.3 +/- 0.2%, 7.1 +/- 4.6%, and 6.0 +/- 1.5%, respectively. Both biliary and urinary excretions of mitoxantrone and its metabolites remained linear over the range of concentrations routinely used in clinic. Metabolism of mitoxantrone was first studied using rabbit hepatocytes in suspension. Since metabolic rate was slow under these incubation conditions (observation period, 1 h), mitoxantrone metabolism was investigated in primary cultures of rabbit hepatocytes. Mitoxantrone was rapidly accumulated within the cells and metabolized to its various metabolites which rapidly effluxed in the extracellular medium. After a 48-h exposure of hepatocytes to a broad range of mitoxantrone concentrations (1 to 20 microM), it could be seen that (a) drug accumulation and metabolism did not exhibit saturation processes, (b) mitoxantrone was the main intracellular form, while (c) metabolites rapidly effluxed in the extracellular compartment and (d) the monocarboxylic acid derivative represented the main extracellular metabolite. This data demonstrates the important role played by the liver in the pharmacokinetic behavior of mitoxantrone and suggests a careful drug monitoring in patients with severe liver dysfunction. PMID- 2912556 TI - Sensitization of noncycling human diploid cells to X-irradiation by pretreatment with 9-beta-D-arabinofuranosyladenine. AB - The interactions between X-irradiation and 9-beta-D-arabinofuranosyladenine (ara A) were studied in confluent, density-inhibited cultures of normal human diploid fibroblast cell strain AG1522. ara-A (0.1 to 3.0 x 10(-3) M) was added to the cultures either 2 or 24 h prior to irradiation. The cells were subcultured at low density to measure the surviving fraction either immediately after irradiation, or they were returned to the incubator in the continued presence of ara-A for an additional 4 or 24 h. In cells subcultured immediately after irradiation, pretreatment with ara-A greatly enhanced cell killing by X-rays in a concentration-dependent fashion. The D0 of the survival curve decreased from 143 cGy to 74 or 49 cGy following pretreatment with 1.0 or 3.0 x 10(-3) M ara-A, respectively. ara-A by itself had little effect on the cloning efficiency of nonirradiated cells at concentrations up to 10(-3) M, but higher levels were cytotoxic. When subculture was delayed for 4 or 24 h, the enhancement in survival reflecting potentially lethal damage recovery was not reduced by continuing incubation with ara-A at concentrations up to 10(-3) M. Higher levels significantly inhibited potentially lethal damage repair, as well as producing marked sensitization. With 24-h delayed subcultivation, the D0 of the survival curve decreased from 324 cGy to 63 cGy following incubation with 3.0 x 10(-3) M ara-A. These results indicate that pretreatment with nontoxic concentrations of ara-A can markedly sensitize human cells to the lethal effects of X-rays. This effect appears to be independent of its ability to inhibit postirradiation cellular recovery processes. PMID- 2912557 TI - Promotion by neurotensin of gastric carcinogenesis induced by N-methyl-N'-nitro-N nitrosoguanidine in Wistar rats. AB - The effects of neurotensin on the incidence and histology of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine were investigated in Wistar rats. Rats were given 100 or 200 micrograms per kg of body weight of neurotensin s.c. every other day in depot form after 25 wk of p.o. treatment with the carcinogen. Prolonged alternate-day administration of neurotensin at 200 micrograms per kg of body weight resulted in a significant increase in the incidence of gastric cancers of the glandular stomach by Wk 52. However, it did not influence the histological appearance of the gastric cancers. Furthermore, it caused a significant increase in the labeling indices of the epithelial cells of the antrum and of gastric cancers. In contrast, the administration of neurotensin at 100 micrograms per kg of body weight had a slight, but not significant, influence on the development of gastric cancers. These findings indicate that neurotensin promotes gastric carcinogenesis, and that this effect may be related to its effect in increasing proliferation of epithelial cells in the antral mucosa and in gastric cancers. PMID- 2912558 TI - Studies on the control of gene expression of the carcinoembryonic antigen family in human tissue. AB - The control of expression of genes of the carcinoembryonic antigen family was investigated in 22 specimens of malignant and nonmalignant human colonic tissues. These surgical specimens included seven colonic adenocarcinomas that were compared with normal adjacent colonic mucosal tissues from the same individual. mRNA preparations from all colonic tissues expressed three bands of 3.5, 3.0, and 2.6 kilobases on Northern blots probed with carcinoembryonic antigen (CEA) complementary DNA probe while normal liver and spleen were negative. The major band of 3.0 kilobases was 6 to 10 times more intense in the colon tumor specimens than in the matched normal mucosa. However, the tumor/normal ratios of immunoreactive CEA in these pairs varied from 2- to greater than 100-fold. Furthermore, there was no direct proportionality between mRNA levels and gene product expression, suggesting that the known variations in CEA expression in human colonic tissues result from both transcriptional and posttranscriptional control mechanisms. Southern blots of DNA from these specimens did not reveal any gene rearrangements or amplifications accompanying expression. Finally, Southern blots of DNA digested with methylation-sensitive endonucleases and probed with a genomic DNA fragment upstream of CEA gene coding regions demonstrated that CEA expression is correlated with a decreased level of methylation in the 5' region of the CEA gene. PMID- 2912559 TI - Monoclonal antibody against human colonic sulfomucin: immunochemical detection of its binding sites in colonic mucosa, colorectal primary carcinoma, and metastases. AB - Previous studies using metabolic labeling of fresh colonic mucosa and colorectal carcinoma with [35S]sulfate followed by biochemical analysis demonstrated that the amount of a sulfated high-molecular-weight glycoprotein expressed in primary colorectal carcinoma was lower than that in normal mucosa, and that the amount further decreased in liver metastases. This suggested that this sulfated molecule represented a sulfomucin previously defined by histochemical reactivity with a cationic dye. We have extracted and partially purified this high-molecular-weight sulfated glycoprotein from normal human colonic mucosa. We immunized mice with the partially purified sulfomucin and generated hybridomas. One cloned hybridoma, designated as 91.9H, produced a monoclonal antibody strongly reactive with a component which migrated at an identical position as the metabolically [35S]sulfate-labeled high-molecular-weight glycoprotein after polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The reactive molecules appeared to have a polydisperse nature with a molecular weight ranging between 400,000 and 900,000. The [35S]sulfate-labeled high-molecular-weight glycoprotein was bound to Staphylococcus Protein A-agarose coated with this monoclonal antibody but did not bind to unconjugated Protein A-agarose. The immunoprecipitated substance also migrated at an apparent molecular weight range of 400,000 to 900,000. The reactivity of monoclonal antibody 91.9H with the extracts of normal mucosa, colorectal primary carcinoma, and metastasis was compared by dot blot assay on a nitrocellulose membrane. This antibody was more reactive with the extracts of mucosa adjacent to carcinoma tissues than with the carcinoma extracts. Primary tumors showed higher reactivity than metastases in most of the cases. These results strongly suggest that this antibody is specific to colonic sulfomucins or at least to mucins closely related to colonic mucins previously identified by metabolic labeling with [35S]sulfate. PMID- 2912560 TI - Expression of the tumor-specific and calcium-binding protein oncomodulin during chemical transformation of rat fibroblasts. AB - An in vivo-in vitro approach to studying neoplastic development in carcinogen exposed rat fibroblasts was evaluated. In the model described, oncomodulin (Mr 12,000; pI 3.9), a tumor-associated and Ca2+-binding protein, was used as a specific marker of malignant transformation. A rapidly proliferating granulation tissue was exposed in vivo or in vitro to potent carcinogens like N-methyl-N' nitro-N-nitrosoguanidine and procarbazine. As an endpoint of transformation anchorage independent (AI) colony formation in the soft agar assay was chosen. Exposure to various doses of N-methyl-N'-nitro-N-nitrosoguanidine in vivo or in vitro, or to procarbazine in vivo, led to induction of AI, transformed cells. Exposure of the cells to various doses of procarbazine in vitro produced neither formation of AI cells in the agar nor expression of oncomodulin in extracts of the exposed cell population. Almost all of the chemically induced AI cell lines tested have been found to be tumorigenic in athymic mice. In contrast, a very low rate (zero to two colonies per 10(6) cells tested) of spontaneous AI populations derived from untreated cells. None of these control AI colonies yielded tumors. In our transformation assay the appearance of neoplastic phenotypes seems very rapid, probably due to the increased cell division at the time of carcinogen exposure. Expression of oncomodulin was found in extracts of transformed cells harvested from agar colonies, derived from carcinogen-exposed granulation tissue, but not from normal, untreated fibroblasts, as shown by two-dimensional polyacrylamide gel electrophoresis and high-performance liquid chromatographic analysis, as well as 45Ca2+-transblot electrophoresis. The presence of oncomodulin in extracts of transformed cells correlates well with the chemically induced colony formation in the soft agar assay. Oncomodulin might be a suitable neoplastic marker to study chemical carcinogenesis. PMID- 2912561 TI - Comparison of DNA-protein cross-links induced by 4'-(9-acridinylamino) methanesulfon-m-anisidide and by gamma-radiation. AB - The antitumor agent 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA) inhibits topoisomerase II activity through the formation of a complex of DNA and covalently bound enzyme which, upon protein denaturation, yields DNA breaks (single strand breaks). In the present study, this complex served as a standard for analysis of radiation-induced DNA-protein cross-links (DPC). Following the treatment of exponentially growing mouse L929 cells with 0-100 ng/ml of m-AMSA for 1 h, a linear dose-dependent increase was found in the amount of DNA retained on nitrocellulose filters during subsequent analysis. This result indicates that the assay can detect DPC that have a single protein bound to each DNA fragment. The results of fractionation of nuclear DNA show that m-AMSA induces 20- to 45 fold more DPC in nuclear matrix-associated DNA than in the majority distal loop DNA, supporting the notion that topoisomerase II is located at the nuclear matrix. The frequency of single strand breaks induced by m-AMSA, which should be equal to the frequency of DPC, was determined by alkaline elution. Results of the alkaline elution assay could be correlated with the percentage of DNA retained on nitrocellulose filters; i.e., 1% DNA retention corresponded to 2560 DPC per log phase L929 cell, which has been determined to have a DNA content of 22.25 pg. Using this standard curve, DPC induced by gamma-irradiation in air were estimated to be formed at a frequency of 133 DPC/cell/Gy, a frequency approximately 3% that of gamma-ray-induced single strand breaks. The radiation dose response for DPC production was unaffected by the high levels of DPC present in cells previously treated with m-AMSA. In addition, DPC induced by m-AMSA were rapidly reversed after the removal of the drug, in contrast to a slower removal of DPC induced by gamma-radiation. These observations suggest that although m-AMSA and gamma radiation both preferentially induce DPC with matrix-attached DNA, they produce independent types of DPC. PMID- 2912562 TI - In vitro hepatotoxicity of SR 4233 (3-amino-1,2,4-benzotriazine-1,4-dioxide), a hypoxic cytotoxin and potential antitumor agent. AB - SR 4233 (3-amino-1,2,4-benzotriazine-1,4-dioxide) is presently undergoing investigation as an antitumor agent because of its high selective toxicity for hypoxic cells in vitro and in vivo. It has been found to be 15 to 200 times more toxic to hypoxic rodent and human cell lines than their normoxic counterparts. We investigated the toxicity of SR 4233 in primary cultures of hepatocytes under various oxygen tensions, ranging from 1% to 20% oxygen. The 50% lethal dose of SR 4233 was found to be 50 times lower in hepatocyte monolayers at 1% O2 versus 20% O2. Even at 4% O2, a concentration that prevails in the pericentral area of the liver under conditions of normal blood flow, SR 4233 was an order of magnitude more toxic than at 20% O2. All samples were analyzed for metabolites, and metabolism was found to be dependent on both the SR 4233 concentration and the oxygen tension. Formation of the major metabolite SR 4317 occurred to the greatest extent at the lowest oxygen concentration and the highest SR 4233 concentration. Very little metabolism occurred at 10 to 20% O2, which is in agreement with data in Chinese hamster ovary cells under aerobic conditions. PMID- 2912563 TI - Inhibition of experimental liver tumor growth in mice by liposomes containing a lipophilic muramyl dipeptide derivative. AB - The ability of liposomes containing a synthetic lipophilic muramyl dipeptide derivative, N-acetylmuramyl-L-alanyl-D-isoglutamyl-sn-glycerol dipalmitate (MDP GDP), to inhibit the growth of experimental B16-F1 melanoma liver metastases in syngeneic C57BL/6 mice has been determined. Multiple i.v. injections of distearoylphosphatidylcholine:dimyristoylphosphatidylglycerol liposomes (1 mumol, 10:1 molar ratio) containing 0.1 to 1 microgram of MDP-GDP given at 3- to 4-day intervals after seeding the livers with tumor cells resulted in a significant inhibition of the number of experimental B16 liver metastases. Control liposomes or free MDP (100 micrograms) failed to affect the number of experimental metastases. A single prophylactic injection of liposomes containing MDP-GDP was equally effective in eliciting a reduction in the number of experimental liver metastases. The ability of liposomal MDP-GDP to inhibit the growth of liver metastases correlated with its ability to induce Kupffer cell tumoricidal activity against the tumor cell targets; activation of C57BL/6 Kupffer cell activity in vitro was most effective with liposomal MDP-GDP, followed by liposomal MDP and free MDP. Only liposomal MDP-GDP and liposomal MDP were able to induce Kupffer cell tumoricidal activity in situ, free MDP being inactive. Liposomal muramyl dipeptide therapy using lipophilic derivatives would appear to be an effective treatment for hepatic metastases derived from primary tumors. PMID- 2912565 TI - Evolutionary trends in cardiovascular catheterization. PMID- 2912564 TI - Toxicity of intrathecally administered cytotoxic drugs and their antitumor activity against an intrathecal Walker 256 carcinosarcoma model for meningeal carcinomatosis in the rat. AB - Meningeal carcinomatosis in humans is refractory to most attempts at therapy and has a grave prognosis. As part of a search for new agents to treat meningeal carcinomatosis, the toxicity of a series of antitumor agents administered through an implanted catheter directly into the cerebrospinal fluid (CSF) of the lumbar spinal cord of 200-g rats has been examined. The highest non-toxic dose (HNTD) of the agents producing no signs of histological damage, motor dysfunction, or neurobehavioral changes was bleomycin (80 micrograms), cytarabine (640 micrograms), dacarbazine (1 microgram), doxorubicin (20 micrograms), 5 fluorouracil (150 micrograms), methotrexate (1000 micrograms), mitomycin C (10 micrograms), and triethylene phosphoramide (800 micrograms). No toxicity was observed at the highest dose that could be administered because of limited solubility of 1,3-bis(2-chloroethyl)-1-nitrosourea (100 micrograms), or diaziquone (70 micrograms). The rat model gave reasonable prediction of the toxicity of antitumor agents that have been administered intra-CSF to humans but with a tendency to underpredict toxicity. The antitumor activity of the agents administered intra-CSF at the HNTD against a Walker 256 carcinosarcoma model for meningeal carcinomatosis in the rat was examined. Diaziquone, doxorubicin, methotrexate, and mitomycin C gave a 25% or greater increase in lifespan and diaziquone and mitomycin C gave some long-term survivors. BCNU, bleomycin and 5 fluorouracil gave less than a 25% increase in lifespan. When mitomycin C was administered intra-CSF at the HNTD and diaziquone at the limit of solubility daily for 4 days there was no toxicity and an increase in survival of Walker 256 carcinosarcoma tumored animals compared to animals administered a single daily dose. Intrathecal diaziquone was more active against meningeal Walker 256 carcinosarcoma than i.v. diaziquone. Intravenous methotrexate had no activity against meningeal Walker 256 carcinosarcoma. We conclude that intra-CSF administration of some anticancer agents such as diaziquone and mitomycin C at doses that do not produce toxicity can significantly increase the survival of rats with experimental meningeal carcinomatosis. PMID- 2912566 TI - Practical considerations in pericardiocentesis. PMID- 2912567 TI - Percutaneous radial artery approach for coronary angiography. AB - Percutaneous entry into the distal radial artery and selective coronarography using a French 5 sheath and preshaded catheters were attempted in 100 patients with a normal Allen test. Cannulation of the radial artery was not possible in ten patients, and selective catheterization of the coronary arteries was unsuccessful in two. Manipulation of catheters presented no problem, and arterial spasm was rarely observed, only before the use of a 23-cm-long sheath. Only two complications without symptoms were observed: arterial dissection of the brachial artery in one patient and occlusion of the radial artery in another. With experience, this approach may become as effective and possibly safer than the transbrachial entry. PMID- 2912568 TI - Variability and reproducibility of quantitative left ventricular angiography. AB - To evaluate the reproducibility of left ventricular angiography for the assessment of left ventricular (LV) function and regional wall motion, two ventriculographies were performed in the 30 degrees right anterior oblique (RAO) projection, at 15-minute intervals, in 19 patients undergoing coronary angiography. Heart rate, left ventricular systolic pressure, and end-diastolic pressure were measured 15 minutes after the first angiography returned to the baseline values (71.0 +/- 14.1 vs. 72.2 +/- 15.5 beats/minute, 153.6 +/- 18.0 vs. 152.8 +/- 19.9 mm Hg, 21.7 +/- 8.6 vs. 20.9 +/- 7.3 mm Hg, respectively). Global and regional LV performance was analyzed by two observers with a computer assisted technique. Intraobserver mean variation of end-diastolic volume and ejection fraction was less than 3% of the control value. Interobserver mean variations for the same parameters were less than 4% of control values. For both observers, there was no significant variation of LV end-diastolic volume and ejection fraction from one study to the other. Under stable hemodynamic conditions, the mean observed variations were, depending on the observer, 5-6% of the control value for LV end-diastolic volume and 5% for ejection fraction. Analysis of segmental wall motion was also highly reproducible. The mean intraobserver variation (% of control value) of wall motion ranged from 4.4% to 9.2%, depending on the sectors studied. The mean interobserver variation, whatever the sector, ranged from 6.9% to 13.5%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2912569 TI - Administration of nifedipine. PMID- 2912570 TI - The state of plant molecular biology: is there a second chance for Ag schools? PMID- 2912571 TI - Autonomous replication in mouse cells: a correction. PMID- 2912572 TI - Germ line transmission and expression of a corrected HPRT gene produced by gene targeting in embryonic stem cells. AB - The deletion mutation in the HPRT-deficient mouse embryonic stem (ES) cell line E14TG2a has been corrected by gene targeting. The presence of plasmid sequences in the correcting vector DNA did not affect the frequency of correction. We have characterized three different HPRT gene structures in correctants. Cells from one corrected clone have been introduced into mouse blastocysts, and germ line transmission of the ES cell-derived corrected gene has been achieved. The corrected gene has the same pattern of expression as the wild-type gene, with the characteristic elevated level of expression in brain tissue. Hence, we have demonstrated the feasibility of introducing targeted modifications into the mouse germ line by homologous recombination in ES cells. PMID- 2912573 TI - On the maternal transfer of 4-aminobiphenyl in rats. AB - The potential for 4-aminobiphenyl (4-ABP) to be transferred from circulating blood into the milk of lactating Sprague-Dawley rats was determined. The distribution of 14C-labeled 4-ABP into milk was examined at time intervals of less than 1, 20, 60, 120, 240 and 480 min after i.v. dose administration. Elimination of radioactivity from blood and milk was determined to be biphasic. The levels of 4-ABP and/or metabolites were lower in milk than in blood at all time points examined. The levels of radioactivity detected in blood declined less rapidly than in milk. That is, the percent of the dose per ml of blood declined from 0.81-0.45, while the percent of the dose per ml of milk declined from 0.38 0.06 during the 8 h time period. The radioactivity present in milk was partially extractable with ethyl acetate with 43% of the radioactivity being extractable at the earliest time point while only 16% was extractable after 8 h. The level of radioactivity associated with the protein precipitate of the milk samples increased from 4-21% within 4 h after treatment. The potential of 4-ABP or its metabolites to exert a genotoxic effect on newborn pups via maternal transfer was also examined. Dams were treated on day 1 post partum and then daily with 4-ABP (10 mg/kg) in corn oil or corn oil alone for 2 weeks. Each experimental group had four liters of pups each containing 5 pups. Pups were sacrificed at 15 days of age, separated by sex and the levels of 4-ABP:DNA adducts in liver determined using 32P-postlabeling. DNA adduct profiles were similar between male and female pups with total adduct levels of 332 and 338 fmol of adducts/mg of DNA, respectively. These results indicate that the genotoxic effects of 4-ABP can be transmitted from exposed dams to the nursing offspring. PMID- 2912574 TI - Enhancement of methylnitrosourea-induced skin tumorigenesis and carcinogenesis in hairless mice by pretreatment with a mitosis-inhibiting epidermal pentapeptide. AB - Two groups of 48 hr/hr mice (24 males, 24 females) were pretreated i.p. with 0.03 nmol of a synthetic epidermal mitosis-inhibiting pentapeptide (EPP), pGlu-Glu-Asp Ser-GlyOH, dissolved in bovine serum albumin solution (BSA) at -6, -3 and 0 h before a topical skin application of 1 mg N-methyl-N-nitrosourea (MNU) in 100 microliters reagent-grade acetone. A control group was pretreated with three solvent injections only -6, -3 and 0 h before application. The results were also compared with a large, historical control group of 333 animals treated once with 1 mg MNU and without any pretreatment. The production of benign and malignant skin tumours was recorded and the results were assessed statistically. There was no statistically significant difference between the large control group without pretreatment and the actual control group pretreated with BSA. Pretreatment with EPP led to significant enhancement of the number of tumour-bearing animals with time and to a very significant increase in the total number of tumours. The group pretreated with EPP also developed more malignant skin tumours. The results are in agreement with earlier findings after i.p. pretreatment with crude skin extracts, hydroxyurea, or when MNU was applied in relation to diurnal rhythms in epidermal cell proliferation. They are also consistent with the assumption that EPP is one of the active growth-inhibitory substances in the epidermal extracts, and support the hypothesis that epidermal basal cells may be more sensitive to MNU-induced carcinogenesis when the rate of cell proliferation is low, because then more cells are in late G1 or early S phase where MNU binding to DNA may be relatively strong. PMID- 2912575 TI - Fluorescence and mass spectral evidence for the formation of benzo[a]pyrene anti diol-epoxide-DNA and -hemoglobin adducts in humans. AB - Highly specific methods are required to detect and quantitate carcinogen macromolecular adducts in humans who are exposed to complex mixtures of chemical carcinogens. High performance liquid chromatography and fluorescence spectroscopy have been used successfully to detect and identify residues of benzo[a]pyrene 7,10/8,9-tetrahydrotetrol (BP-7,10/8,9-tetrol) that were released upon mild acid hydrolysis of human DNA or hemoglobin. Synchronous fluorescence spectroscopy data indicate that levels of benzo[a]pyrene-diol-epoxide-DNA (BPDE-DNA) adducts as high as 1.54 fmol BPDE/micrograms DNA are formed (1 adduct in 5 million nucleotides) in peripheral blood lymphocytes of coke-oven workers; these data were subsequently corroborated by gas chromatography/mass spectroscopy single ion monitoring analysis (m/z 404+). Additionally, among lung cancer patients, 5 samples of tumor DNA were found to be negative and 1 of 4 samples of corresponding lung tissue was found to be positive. Extraction and purification of BP-7,10/8,9-tetrol from the hemoglobin of smokers suggested levels of bound carcinogen in excess of 1 ng BPDE/gm of hemoglobin. High performance liquid chromatography combined with synchronous fluorescence spectroscopy provides a highly specific method for the detection of covalently bound BP residues in both human hemoglobin and DNA. PMID- 2912576 TI - Effect of sulfite on the covalent reaction of benzo[a]pyrene metabolites with DNA. AB - Sulfur dioxide (SO2) potentiates the carcinogenicity of polycyclic aromatic hydrocarbons. To investigate the mechanism of SO2 cocarcinogenesis, the effect of sulfite, the hydrated form of SO2, on the covalent reaction of benzo[a]pyrene (BaP) metabolites with DNA in vitro was measured. [14C]BaP was incubated with rat lung or liver post-mitochondrial supernatant (S9), an NADPH generating system, calf thymus DNA and sodium sulfite (0-20 mM). In the presence of lung S9, covalent reaction increased linearly from 0.66 to 1.20 pmol BaP metabolites per mg DNA with increasing sulfite concentrations. Addition of sulfite to rat liver S9 also increased BaP-DNA adduct formation with BaP-DNA adducts increasing from 80 to 120 pmol per mg DNA. Sulfite altered the amount and pattern of BaP metabolites formed by either lung or liver enzyme preparations. BaP was metabolized more extensively and the amount of water soluble BaP metabolites formed increased significantly with sulfite present. With lung S9, the amount of BaP-tetrols, diols, and phenols increased slightly. With liver S9, diol and phenol formation was significantly lower while tetrol formation was unchanged. Incubation of rat lung S9 with sulfite resulted in formation of glutathione S sulfonate (GSSO3H), a known inhibitor of glutathione S-transferases mediating the conjugation of glutathione (GSH) and BaP epoxides. Our results suggest that sulfite may, by altering the overall metabolic activation and detoxication of BaP, or by reacting directly with DNA, subsequently affect the covalent reaction of BaP metabolites with DNA. These are offered as possible mechanisms to explain the cocarcinogenic effect of SO2. PMID- 2912577 TI - Effect of a Prudhoe Bay crude oil on hepatic and renal peroxisomal beta-oxidation and mixed-function oxidase activities in rats. AB - The effect of oral administration of a Prudhoe Bay crude oil (PBCO) to male rats (PBCO, 2.6 g/kg body weight, daily) for 5-12 days on hepatic and renal microsomal monooxygenase activities and peroxisomal beta-oxidation has been investigated. PBCO administration leads to liver enlargement. This is associated with induction of microsomal cytochrome P-450 levels (1.6- to 2.0-fold) and dependent mixed function oxidase activities (7-ethoxyresorufin-O-deethylase and 7 pentoxyresorufin-O-depentylase, representing cytochrome P-450I and cytochrome P 450IIB isoenzymes respectively, 9- to 15-fold; omega-oxidation of lauric acid representing the cytochrome P-450IVA1 isoenzyme, 1.4- to 1.5-fold) along with peroxisomal beta-oxidation (palmitoyl CoA oxidation, 2- to 5-fold). It was observed that rats exposed to PBCO showed an increase in renal microsomal cytochrome P-450 content (1.6- to 2.3-fold), cytochrome P-450I activity (5- to 8 fold) and omega-oxidation activity (1.3- to 1.4-fold). However, renal peroxisomal beta-oxidation was unaltered. Serum total triglycerides were lowered by 41-46% after PBCO exposure. These results suggest that induction of peroxisomal beta oxidation and possibly mono-oxygenases may be related to the carcinogenic/tumorigenic potential of crude oil. PMID- 2912578 TI - Supplementation with selenium, vitamin E and their combination in gynaecological cancer during cytotoxic chemotherapy. AB - The biochemical responses to 8-week supplementary treatment with selenium and/or vitamin E were evaluated in 41 patients with gynaecological cancer during cytotoxic chemotherapy, in Finland, a selenium-deficient country. After the control course of 1-day treatment with cytostat agents, 11 patients received a combination of selenium and vitamin E (sodium selenate, 200 micrograms/day + vitamin E, 300 mg/day), 11 received selenium (sodium selenate, 200 micrograms/day) and seven received vitamin E (300 mg/day) as supplementary therapy, while 12 patients had no supplementary drugs. Sodium selenate alone and combined with vitamin E significantly increased the serum selenium levels, but the activity of serum glutathione peroxidase (GSH-Px) increased significantly only in the selenium- and vitamin E-treated patients with low initial GSH-Px activity. The cytotoxic chemotherapy did not change the activity of GSH-Px, while the concentrations of lipid peroxides decreased. Sodium selenate alone or with vitamin E did not modify this decrease. Sodium selenate alone significantly decreased the capacity of the platelets to produce thromboxane A2; it increased high-density lipoprotein cholesterol levels and prevented the cytotoxic chemotherapy-associated increase of creatine kinase. Selenium supplementation might thus be beneficial during cytotoxic chemotherapy in ovarian cancer patients with low selenium levels. PMID- 2912579 TI - Determination of S-phenylmercapturic acid in the urine--an improvement in the biological monitoring of benzene exposure. AB - In an inhalation study rats were exposed to different doses of benzene, ranging from 1 to 500 p.p.m. The urine was sampled during the inhalation period of 8 h and for 24 h after exposure. S-Phenylmercapturic acid (S-PMA) in the urine was determined by amino acid analysis. Phenol was measured by gas chromatography/mass spectrometry. In both cases the correlation between benzene uptake and the excretion of the urinary metabolites was significant at the level of P = 0.01. The same significant correlation (P = 0.01) was demonstrable after i.p. administration of benzene at doses between 0.7 and 140.0 microliters/kg body weight. In the case of two collectives of workers who were exposed to air concentrations of up to 0.15 p.p.m. for 8 h and of up to 1.13 p.p.m. for 12 h respectively, the amount of S-PMA in the first urine samples after the shift was significantly higher than in samples collected at the beginning of the shift (P = 0.01). In the first collective the mean values and the standard deviations of the S-PMA concentrations in the samples at the beginning of the shift were 12.0 +/- 16.7 compared with 48.5 +/- 64.5 micrograms/g creatinine at shift end. In the second collective they were 25.1 +/- 25.1 compared with 70.9 +/- 109.2 micrograms/g creatinine. The level of significance of the difference between the concentration values of S-PMA at the beginning and end of the shift was P = 0.01. The phenol concentration did not differ significantly. These results suggest that S-PMA can be regarded as a useful indicator for monitoring individuals and collectives exposed to benzene at levels even less than 1 p.p.m. PMID- 2912580 TI - Tumour-promoting and hyperplastic effects of phorbol and daphnane esters in CD-1 mouse skin and a synergistic effect of calcium ionophore with the non-promoting activator of protein kinase C, sapintoxin A. AB - Using an 18 week two-stage protocol we have compared the tumour-promoting properties of a range of phorbol and daphnane esters on female CD-1 mice. The induction of epidermal hyperplasia in this mouse strain by these compounds has also been assessed by comparison with the standard phorbol ester, 12-O tetradecanoylphorbol-13-O-acetate (TPA). Two compounds, sapintoxin D (SAP D) and thymeleatoxin A (TA) (a daphnane structurally related to the second-stage promoter mezerein) were shown to be second-stage promoters using 5 nmol TPA as a first-stage promoter and 0.2 mumol 7,12-dimethylbenz[a]anthracene (DMBA) as initiator. Both compounds at a dose of 17 nmol were hyperplasiogenic. Two further derivatives, sapintoxin C (SAP C) and 4 alpha-sapinine (alpha-SAP) were inactive as promoters and hyperplastic agents. 4 alpha-sapinine, which prevents in vitro stimulation of protein kinase C (PKC), by 12-O-tetradecanoylphorbol-13-O-acetate (TPA) failed to inhibit significantly TPA-induced promotion and hyperplasia at a dose of 20 nmol and 100 nmol respectively. Sapintoxin A (SAP A), a potent activator of PKC, was neither a complete nor second-stage promoter at doses of up to 20 nmol. A series of in vivo and in vitro experiments which were carried out to determine the metabolic fate of this compound under experimental conditions showed that SAP A was not metabolized to any significant extent up to 48 h. When SAP A was co-administered with sub-hyperplastic doses of the calcium ionophore A23187 (5 micrograms and 10 micrograms) tumours appeared in a dose-dependent manner. This combination was also hyperplasiogenic in mouse skin. SAP A may be a useful probe for studying the involvement of PKC isozymes in tumour promotion and cell proliferation. PMID- 2912581 TI - Transfection of a human cytochrome P-450 gene into the human lymphoblastoid cell line, AHH-1, and use of the recombinant cell line in gene mutation assays. AB - We have demonstrated that the human cytochrome P1-450 gene can be transfected into the AHH-1 human lymphoblastoid cell line using the pHEBo vector and hygromycin selection. The transfected gene was expressed when regulatory sequences derived from the herpes simplex virus thymidine kinase gene were incorporated in appropriate orientations. Gene expression was monitored at the enzyme level using assays for 7-ethoxyresorufin deethylase, 7-ethoxycoumarin deethylase and benzo[a]pyrene hydroxylase activities. Bulk transformed cell populations had 2- to 3-fold more of these enzyme activities compared with control populations. Subclones of the bulk population expressing still higher levels of 7-ethoxyresorufin deethylase activity were also obtained. Expression of the transfected cytochrome P1-450 gene was stable for 20-30 days in the presence of hygromycin B. The transformed cell populations were found to be suitable for use in gene locus mutation assays and the mutagenicity of aflatoxin-B1 and 2 acetylaminofluorene (AAF) were examined. Aflatoxin-B1 was found to be 2-3 times more mutagenic to cells bearing the transfected cytochrome P1-450 activity as compared with control cells. In contrast, no difference in AAF mutagenicity was observed. Analysis of the AAF metabolite profile indicated that cells expressing the transfected cytochrome P1-450 gene produced 8-fold more N- and 7-hydroxy-AAF than control cells. The similarity in mutagenic responses between control cells and cells bearing the transfected cytochrome P1-450 gene may be due to the low deacetylase activity of AHH-1 cells. These observations indicate that this vector and expression system are suitable for introducing novel metabolic activities into the AHH-1 cell line. PMID- 2912582 TI - Effect of chronic dietary ethanol consumption on the initiation and promotion of chemically-induced esophageal carcinogenesis in experimental rats. AB - Preliminary dose finding studies showed that 22 mg/kg of N nitrosomethylbenzylamine (NMBZA) delivered over 5 days did not induce esophageal lesions, but 18 mg/kg administered over a period of 2 or 3 weeks did induce these lesions. Based on these results, Sprague-Dawley rats were treated with 2.5 mg/kg NMBZA three times a week for 3 weeks to initiate esophageal carcinogenesis. The experimental animals were administered isocaloric ethanol diet either before and during NMBZA initiated carcinogenesis, or after initiation as a tumor promoter. The esophagi of rats that died or who were terminated at 18 months of age were examined for nodules and tumors. When ethanol was administered before and during initiation, the mean frequency of esophageal lesions was 8.04 +/- 3.04/rat with an average size of 1.44 +/- 0.27 mm versus 12.41 +/- 2.12/rat and 0.92 +/- 0.17 mm respectively for the controls. Only three out of 13 of the ethanol-fed rats had tumors (mainly squamous papillomas) versus 10 out of 26 of the control-fed animals. Ethanol consumption before and during initiation, therefore, decreased the incidence of esophageal nodules and tumors. With ethanol administered as a promoter, on the other hand, while incidence of the total lesions was not affected appreciably, the incidence of tumors was remarkably increased. With ethanol promotion the mean frequency of lesions was 8.75 +/- 1.07/rat with an average size of 1.02 +/- 0.09 mm versus 10.94 +/- 1.49/rat and 1.32 +/- 0.13 mm respectively for the controls. In this case, the ethanol-consuming rats had tumors in 14 out of 75 animals versus one small tumor in 32 of the controls. The results indicate that the occurrence of esophageal tumors is inhibited by simultaneous ethanol administration, but promoted when ethanol is administered post-initiation ostensibly by allowing extensive dysplastic proliferation of the carcinogen-induced lesions. PMID- 2912583 TI - The molecular structures of 11-methyl and 1,12-dimethylbenz[a]anthracene: purely theoretical semi-empirical AM1 calculations are able to predict accurate structures of these polycyclic hydrocarbons. AB - Semi-empirical self consistent field calculations are reported on 11-methyl and 1,12-dimethylbenz[a]anthracene using the AM1 method. Comparison of the results of complete geometry optimizations with experimental X-ray structures shows that it is now possible to compute the structure of these large molecules with errors in bond lengths of less than 0.02 A and in bond angles of less than 1.5 degrees. PMID- 2912584 TI - Hydrolysis of bisphenol A diglycidylether by epoxide hydrolases in cytosolic and microsomal fractions of mouse liver and skin: inhibition by bis epoxycyclopentylether and the effects upon the covalent binding to mouse skin DNA. AB - Synergistic interactions have been reported in the carcinogenicity of two epoxy resin components to mouse skin. A mixture of bisphenol A diglycidylether and bis epoxycyclopentylether was highly carcinogenic, despite the fact that neither compound gave positive results when applied individually. To elucidate the mechanism of this synergistic interaction we have investigated the effects of bis epoxycyclopentylether upon the hydrolysis and DNA-binding of bisphenol A diglycidylether. This glycidylether was rapidly hydrolysed by microsomal and cytosolic fractions of mouse liver and skin. In three different mouse strains the specific epoxide hydrolase activities were 28.3-48.5; 33.0-38.8; 7.9-10.2 and 0.85-0.98 nmol/mg protein/min for liver microsomal and cytosolic and skin microsomal and cytosolic fractions respectively. This is the first demonstration of an epoxide hydrolase activity in skin cytosolic fractions. Bis epoxycyclopentylether inhibited the microsomal activities. This inhibition appeared to be slightly more effective with microsomal fractions from liver. The effect of this inhibition upon the binding of bisphenol A diglycidylether to mouse skin DNA was investigated using bisphenol A diglycidylether radiolabelled at two different positions. When high doses of bisphenol A diglycidylether were applied to the mouse skin one major DNA adduct was observed which was identified as a glycidaldehyde adduct. This adduct was not detectable at the lowest bisphenol A diglycidylether dose tested, unless bis epoxycyclopentylether was applied simultaneously. These findings suggest that glycidaldehyde may be formed from bisphenol A diglycidylether. At low doses, however, the epoxide groups are hydrolysed before glycidaldehyde can be formed, unless the epoxide hydrolase is inhibited. Such inhibition and the associated increased production of glycidaldehyde may account for the potentiation of the carcinogenic response in the epoxide mixture. PMID- 2912585 TI - Hypersensitivity of human tumor xenografts lacking O6-alkylguanine-DNA alkyltransferase to the anti-tumor agent 1-(4-amino-2-methyl-5-pyrimidinyl)methyl 3-(2-chloroethyl)-3-nitros ourea. AB - Human tumor cell strains having different activities of O6-alkylguanine-DNA alkyltransferase (ATR) were transplanted into nude mice and chemotherapeutic responses of tumor xenografts were compared after intraperitoneal injection of the anti-tumor drug 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3 nitrosourea (ACNU). The tumor strains used were four Mer+ strains possessing high ATR activity and three Mer- strains lacking this activity. Included in these Mer+ strains was a clone 5'dD which expresses the Escherichia coli ATR in Mer- HeLa cells and thus shows the Mer+ phenotype. All the Mer- tumor xenografts were much more sensitive than tumors of Mer+ strains, including the clone 5'dD; after the highest ACNU dose (three injections of 50 mg/kg), some Mer- tumors disappeared completely and the growth of other tumors was severely retarded, whereas all Mer+ tumors continued to grow. These results demonstrate that ATR activity in tumor cells is a major determinant of tumor response to ACNU, and further suggest that measurement of ATR activity in biopsy specimens may provide a useful guide to predict the response to chemotherapy. PMID- 2912587 TI - Dose-dependence and stability of cisplatin binding to tissue DNA and blood proteins in rats. AB - Two experiments were carried out by using atomic absorption spectroscopy on the stability and dose-dependence of cisplatin [cis-diamminedichloroplatinum (II)] binding to blood proteins and tissue DNA of male Han/Wistar rats. The dose dependence was studied by injecting 17 rats i.p. either with cisplatin (4.4, 8.0 or 11.0 mg/kg) or 0.9% NaCl (controls). The Pt concentrations in blood proteins (plasma proteins and hemoglobin) and DNAs of different tissues (kidney, liver, lung and testis) were measured 24 h after the treatment. The binding of cisplatin to blood proteins and tissue DNAs correlated with each other and the dose. The stability was studied by treating 17 rats i.v. with 8.0 mg cisplatin/kg. The Pt concentrations in kidney, liver and lung DNA were determined 5 h, 1, 3 or 5 days after the treatment. The disappearance of Pt was faster in kidney DNA than in liver or lung DNA; in 5 days the Pt concentration in kidney DNA decreased by 63% while the Pt content in liver or lung decreased by 40%. Both of these experiments showed that the binding of cisplatin to kidney DNA exceeded the other tissue DNAs examined. Testicular DNA showed the lowest level of binding. The present animal data suggest that the platination level of blood proteins may be used as a measure of Pt concentration in tissue DNA. PMID- 2912586 TI - Activation of the food-derived mutagen 2-amino-1-methyl-6-phenylimidazo[4,5 b]pyridine by rabbit and human liver microsomes and purified forms of cytochrome P-450. AB - The specificity of rabbit cytochrome P-450 involved in the mutagenic activation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) was assessed using control and induced rabbit liver and lung microsomes, and six purified forms of cytochrome P-450. The number of revertants produced/2.5 micrograms PhIP by control rabbit liver was 260 +/- 196/10 micrograms of microsomal protein (mean +/ SD; n = 3), and this increased to 1265 +/- 248 when 2,3,7,8-tetrachlorodibenzo-p dioxin (TCDD)-induced liver microsomes were used as the activation source in the Ames test. Microsomes form phenobarbital-, rifampicin- and acetone-pretreated rabbits showed no increase in activity over controls. Control lung microsomes did not activate PhIP to a mutagen, whereas TCDD-induced lung microsomes produced 1443 +/- 136 (mean +/- SD; n = 4) Ames/Salmonella revertants/100 micrograms protein. In reconstitution experiments cytochrome P450 forms 4 and 6 were found to be efficient activators of PhIP to a mutagen Form 6 was 3.1-fold more active than form 4 and produced 4577 revertants/10 pmol with a 20-min preincubation step in the Ames test. Cytochrome form 5 produced 17 revertants/10 pmol and forms 2, 3b and 3c were not active in metabolizing PhIP to a mutagen. A highly significant statistical correlation existed between the capacity of control and induced liver microsomes to activate PhIP to a mutagen and their cytochrome P-450 form 4 (r = 0.97, r2 = 0.94) and form 6 (r = 0.95, r2 = 0.90) content. These data strongly support the involvement of polycyclic hydrocarbon-inducible forms of cytochrome P450 in the activation of PhIP in the rabbit. Anti-rabbit forms 4 and 6 IgGs recognized proteins in seven human liver microsomes of comparable mol. wt to rabbit cytochrome P-450 forms 4 and 6. However, no correlation existed between the content of these proteins and the capacity of human liver microsomes to activate PhIP. PMID- 2912588 TI - Comparative tumorigenicity of 6-nitrochrysene and its metabolites in newborn mice. AB - The tumorigenic activities of 6-nitrochrysene and its metabolites were evaluated in the newborn mouse model. Groups of mice were treated with the appropriate compounds in DMSO by i.p. injections on the 1st, 8th and 15th day of life. Seven hundred nmol/mouse of 6-nitrochrysene induced significant incidences and multiplicities of lung tumors in both sexes; only males were susceptible to liver tumor induction. At 100 nmol/mouse, 6-nitrochrysene had significant tumorigenicity in both lung and liver but was less active than at the higher dose. Administration of 100 nmol/mouse of 6-nitrochrysene, only on day 1, caused about the same tumor yield as was observed after treatment with 700 nmol/mouse given over 3 days. Among the metabolites of 6-nitrochrysene which were tested at 100 nmol/mouse, 6-nitrosochrysene and 6-aminochrysene were significantly less active in the lung and in the liver than 6-nitrochrysene. In the lung, trans-1,2 dihydro-1,2-dihydroxy-6-nitrochrysene and trans-1,2-dihydro-1,2-dihydroxy-6 aminochrysene had activities comparable to those observed in mice treated with equimolar doses of 6-nitrochrysene. In the liver, trans-1,2-dihydro-1,2-dihydroxy 6-nitrochrysene was more active than 6-nitrochrysene based on the number of tumors per mouse. These observations support our hypothesis that 6-nitrochrysene is metabolically activated by ring-oxidation to trans-1,2-dihydro-1,2-dihydroxy-6 nitrochrysene, followed by nitro-reduction to trans-1,2-dihydro-1,2-dihydroxy-6 aminochrysene and, finally, oxidation to a diol-epoxide. PMID- 2912589 TI - Inhibition of the induction of ornithine decarboxylase activity by 12-O tetradecanoylphorbol-13-acetate in mouse skin by sphingosine sulfate. AB - We investigated the effect of sphingosine sulfate on the induction of ODC (ornithine decarboxylase) activity by TPA (12-O-tetradecanoylphorbol-13-acetate) in mouse skin. When applied topically to the shaved skin of SENCAR mice at dosages of 10-40 mumol per animal, 30 min before the superficial application of 8.5 nmol of TPA, sphingosine sulfate dramatically inhibited the induction of ODC activity by the tumor promoter. Significant inhibition of TPA-induced ODC activity was observed at 4, 6 and 8 h after TPA treatment in separate studies. The results indicate that sphingosine sulfate is an effective inhibitor of ODC induction by TPA in mouse skin. PMID- 2912590 TI - Genotoxic effects of intragastrically administered benzo[a]pyrene in rat liver and intestinal cells. AB - The genotoxic effects of intragastrically administered benzo[a]pyrene (BaP) were studied in isolated rat liver and intestinal cells. We found that BaP was unable to induce unscheduled DNA synthesis in rat parenchymal liver cells in vivo. In contrast, alkaline elution showed that at 5 h after administration of BaP a considerable number of alkali-labile sites was present in the DNA of both intestinal cells and parenchymal liver cells, but not in that of non-parenchymal liver cells. The possibility is discussed that these sites were induced by radical intermediates, generated during the metabolization of BaP. PMID- 2912591 TI - Development of neoplastic phenotype following transfection of HNF cells with sarcoma DNA. AB - DNA isolated from chondrosarcoma cells effectively transformed NIH-3T3 cells and human foreskin fibroblasts. The transfected NIH-3T3 cells, directly implanted three or four passages later, formed progressively growing tumors (greater than or equal to 2.0 cm in diameter) subcutaneously in nude mice. No metastasis was evident upon pathological examination of the tumor bearing mice. Transfected human foreskin fibroblasts that exhibited anchorage independent growth formed only small tumors in nude mice (less than 0.6 cm in diameter). The transfected human cells which exhibited anchorage independent growth reacted with the monoclonal antibody 345.134S, specific for an epitope expressed by human sarcoma cells. The transfected NIH-3T3 cells did not exhibit reactivity with the same monoclonal antibody. Southern blot analysis of the DNA prepared from the transfected NIH-3T3 cells, that developed as a progressively growing tumor in a nude mouse, revealed the presence of human repetitive DNA sequences. PMID- 2912592 TI - Peroxidative in vitro metabolism of diethylstilbestrol induces formation of 8 hydroxy-2'-deoxyguanosine. AB - The generation of superoxide and hydroxyl radicals is known to be implicated in the hydroxylation of 2'-deoxyguanosine (dG) at the C-8 position and of guanine base residues in DNA. It was also shown previously that in the presence of horseradish peroxidase, hydrogen peroxide and Fe3+ - EDTA complex, diethylstilbestrol (DES) induces single strand breaks in DNA, caused by the production of superoxide anion (O2-) and hydroxyl (OH.) radicals. By means of high-pressure liquid chromatography and electrochemical detection a strong indication is adduced that dG is oxidized to 8-hydroxy-2'-deoxyguanosine during peroxidative in vitro metabolism of DES, which might be at the basis of DES induced cell transformation. PMID- 2912594 TI - Regional differences in the in vivo synthesis and degradation of myosin subunits in rabbit ventricular myocardium. AB - To test for regional differences in the rates of synthesis and degradation of contractile proteins during normal physiological growth of the heart in vivo, fractional rates of protein accumulation and synthesis were assessed for total protein, myosin heavy chain, myosin light chain, phosphorylatable myosin light chain, and actin in the right and left ventricular free walls of growing, New Zealand White rabbits. Fractional rates of protein accumulation were determined from regional protein content growth curves of total and individual myofibrillar proteins measured in 82 animals ranging from 1 day to 9 weeks of age. In vivo right and left ventricular fractional rates of protein synthesis were determined by the [3H]leucine constant infusion method in 9-week-old rabbits. At this age, right and left ventricular fractional accumulation rates for total protein, myosin subunits, and actin were found to be identical, thus allowing for the comparison of the effect of regional hemodynamic load on protein degradation independent of its effect on growth. Total protein and individual myofibrillar protein fractional degradative rates were then derived as the difference between fractional rates of synthesis and accumulation. The results indicate increased fractional synthesis and degradation of myosin heavy chain and light chains, but not actin, in the left compared to the right ventricular free wall. Accelerated left ventricular replacement of myosin subunits may be related to regional differences in hemodynamic load. These results help explain the apparent increase in the in vivo rate of myocardial protein degradation observed in several experimental models of ventricular hypertrophy. PMID- 2912593 TI - Protection against polycyclic aromatic hydrocarbon-induced skin tumor initiation in mice by green tea polyphenols. AB - Green tea is a popular beverage in China and Asia and has been shown to possess antipyretic, diuretic and several other pharmacological activities. The major constituents of green tea are polyphenols which have been found to possess antioxidant and antimutagenic properties. In this study green tea polyphenols (GTP) were evaluated as an anti-initiating agent against the skin tumorigenicity induced by polycyclic aromatic hydrocarbons (PAHs) in mice. In a complete skin tumorigenesis protocol using 3-methylcholanthrene the topical application of GTP to female BALB/c mice resulted in substantial protection against the onset and subsequent development of tumors. In the two-stage skin tumorigenesis protocol using 7,12-dimethylbenz[a]anthracene (DMBA) as the initiating agent followed by twice weekly applications of 12-O-tetradecanoylphorbol-13-acetate; (TPA) as tumor promoter, topical application of GTP to female SENCAR mice afforded significant protection against skin tumorigenicity. Oral feeding of GTP in drinking water to female SENCAR mice also protected against skin tumorigenesis in DMBA - TPA treated animals. GTP when administered topically or orally significantly inhibited PAH - DNA adduct formation in epidermis after topical application of [3H]benzo[a]pyrene or [3H]DMBA. Our results suggest that GTP has substantial anti skin-tumor-initiating activity against PAHs and could prove useful in protecting against some forms of human cancer. PMID- 2912596 TI - Effect of reduced energy metabolism and reperfusion on the permeability and morphology of the capillaries of an isolated rete mirabile. AB - The effects of reduction in energy metabolism were explored in the eel rete mirabile, an organ composed predominantly of capillaries. In vitro experiments showed that glycolysis is the major pathway of energy production in this capillary tissue, and that iodoacetate, KCN, and low PO2 in combination markedly reduce its ATP generation. When in situ energy generation was inhibited by this combination during countercurrent perfusion of the arterial and venous capillaries of the rete, an approximate doubling of the intercapillary barrier permeability for human [125I]albumin, [14C]sucrose, and 22Na was found. Structural damage was evident, but the intercellular junctions remained intact. The effect of cessation of flow for 30 minutes, followed by reperfusion, was then explored. Stasis alone altered the structure, chiefly of the venous capillary endothelium, but not the permeability of the intercapillary barrier. Stasis with a hypoxic medium containing the inhibitors of energy generation, followed by reperfusion with oxygenated control medium, resulted in a progressive breakdown of the intercapillary barrier, with a threefold to fourfold increase in solute (labeled albumin, sucrose, and sodium) permeability, evolving during early reperfusion, but no change for labeled water permeability. Morphologically, the endothelial cells, especially those in venous capillaries, showed substantial damage; they appeared vacuolated, their cytoplasm was extracted, and cytoplasmic and membrane debris were found in the lumen; intercellular junctions remained intact. Local pericyte detachment with interstitial edema also appeared. Thus, stasis and reperfusion amplified the effects of reduction in energy generation and hypoxia on both permeability and morphological change. PMID- 2912595 TI - Electrophysiological properties of cultured dog myocytes obtained by endomyocardial biopsy. AB - Right ventricular cardiac tissue (10-20 mg wet weight) was obtained from anesthetized adult dogs by endomyocardial biopsy. The biopsy could be repeated in one dog every 2 weeks for up to 3 months. Fifty to 200 cardiomyocytes, dispersed with collagenase and trypsin, were collected by centrifugation of the cells with 50% polysucrose-sodium diatrizoate solution (Ficoll-Paque). Single cardiomyocytes were suspended in a minimum essential medium containing 20% fetal bovine serum and 8-bromoadenosine 3': 5'-cyclic monophosphate (0.1 mM) for up to 3 weeks. Approximately 70-80% of the cultured cardiomyocytes were rod shaped after 24 hours (10-20% after 7 days). Cytoplasmic organelles of the cultured cells, examined with a transmission electron microscope, were within the normal range of canine heart morphology in vivo. Resting membrane potential of the cells was about -80 mV when superfused with a Krebs' solution containing 4.7 mM potassium ions. The action potential lasted for 300 msec and had a peak amplitude of about 120 mV. Voltage-clamp experiments demonstrated the presence of an inward calcium current (congruent to 0.9 nA at +9 mV), which was facilitated by isoproterenol (0.1-1 microMs). The background potassium current showed typical inward rectification at potentials more negative than -80 mV. The results indicate that morphological, electrophysiological, and pharmacological properties of the cultured cardiomyocytes were intact. We propose that the culture techniques we have developed can be useful for repeated investigation on functional aspects of cardiac muscles in myocardial disease. PMID- 2912597 TI - Long-term versus intrabeat history of ejection as determinants of canine ventricular end-systolic pressure. AB - We studied the effect of ejection on end-systolic pressure in isolated heart preparations. Ejecting beats were compared with isovolumic beats having the same volume as at end systole. While holding end-systolic volume constant, various stroke volumes, including negative stroke volumes (volume injected during systole), were imposed using a predetermined volume command. After switching contraction mode between ejecting and isovolumic, we measured the immediate and steady changes in end-systolic pressure. In the first isovolumic beat after switching from steady-state ejecting beats, the change in end-systolic pressure was variable, depending on the stroke volume. The end-systolic pressure of the ejecting beat exceeded that of the isovolumic beat on average by up to 18 mm Hg with small stroke volume, but the ejecting end-systolic pressure became lower than isovolumic with either large stroke volume (stroke volume/end-systolic volume less than 0.96) or with negative stroke volume. During the transient phase following a switch from ejecting to isovolumic, the end-systolic pressure gradually decreased to a steady state. Consequently, even in steady state, ejecting end-systolic pressure exceeded isovolumic pressure over a significant range of stroke volume (stroke volume/end-systolic volume less than 1.18). After returning contraction mode from isovolumic back to ejecting, we observed responses that were a mirror image. These results indicated that in addition to negative uncoupling effect, ejection exerts positive effects on ventricular end systolic pressure that are manifest both quickly and gradually. We hypothesized that the mechanism responsible for the positive effect is length-dependent activation via the larger volume (both at the initiation of contraction and averaged over a cardiac cycle) of a beat that ejects compared to one held isovolumic at end-systolic volume. The results with volume injection were consonant with this concept. PMID- 2912598 TI - End-systolic pressure as a balance between opposing effects of ejection. AB - Ejection has previously been thought to exert only negative effects on end systolic left ventricular pressure, via mechanisms like shortening deactivation and the force-velocity relation. Whether ejection also exerted a positive influence on pressure generation was tested by comparing two successive beats: 1) the last beat of steady-state ejection versus 2) a totally isovolumic contraction at the end-systolic volume. In 12 isolated, blood-perfused canine hearts loaded with a simulated arterial system, ejecting end-systolic pressure exceeded isovolumic pressure by approximately 10 mm Hg when ejection fraction was 0.3. With both higher and lower ejection fractions, the excess of ejecting end systolic pressure was smaller; beyond an ejection fraction of roughly 0.5, the trend reversed so that ejecting end-systolic pressure fell below isovolumic pressure. The maximum excess in ejecting end-systolic pressure was quite variable (1-17 mm Hg), but the pattern of its variation with ejection fraction was consistent. A correlate of the positive effect of ejection on ventricular pressure was found in the timing of end systole. For an ejection fraction of 0.4, the systolic duration of ejecting beats was approximately 45% longer than in isovolumic beats (range, 23-67%). Potentially, a positive effect of ejection might be due to a residual influence of the stronger activation of cardiac myofilaments early in ejecting systole during which the sarcomeres were at longer lengths than in the isovolumic beat at end-systolic volume (length-dependent activation). A hypothetical model based on this mechanism reproduced both of the positive effects of ejection that were observed: excess end-systolic pressure and prolonged duration of systole. Thus, the approximate load independence of end systolic pressure could result from the counter balance between opposing influences of ejection. PMID- 2912599 TI - Effects of calcium channel antagonists on carotid sinus baroreflex control of arterial pressure and heart rate in anesthetized dogs. AB - Our study was designed to determine whether the calcium channel antagonists verapamil, diltiazem, and nifedipine and the nitrate vasodilator sodium nitroprusside modulate carotid sinus (CS) baroreflex control of mean arterial pressure (MAP) and heart rate (HR). Pentobarbital-anesthetized, vagotomized dogs were surgically prepared for reversible vascular isolation of the CS regions. Open-loop performance of the CS baroreflex was determined under control conditions and after intravenous infusion of each agent for 20 minutes at four rates (nitroprusside: 0.3-10 micrograms/kg/min; verapamil and diltiazem: 1-30 micrograms/kg/min; nifedipine: 0.1-3 micrograms/kg/min). With the CS baroreflex loop closed, each vasodilator decreased MAP from control (nitroprusside: 127 +/- 3 to 69 +/- 5 mm Hg; verapamil: 137 +/- 7 to 86 +/- 5 mm Hg; diltiazem: 137 +/- 9 to 100 +/- 5 mm Hg; nifedipine: 140 +/- 6 to 109 +/- 7 mm Hg). Each compound also caused a dose-dependent downward shift in the open-loop CSP-MAP relations. The higher doses of each vasodilator also depressed the total range of control of MAP (i.e., maximum MAP minus minimum MAP) by the baroreflex and significantly attenuated the peak open-loop MAP/CSP gains (nitroprusside: 1.21 +/- 0.19 to 0.56 +/- 0.12; verapamil: 1.36 +/- 0.16 to 0.64 +/- 0.10; diltiazem: 1.52 +/- 0.34 to 0.89 +/- 0.11; nifedipine: 1.35 +/- 0.20 to 0.83 +/- 0.14) but did not alter the CSP at which the peak gain was manifest. Only verapamil and diltiazem significantly shifted downward the CSP-HR relations, whereas none of the drugs affected the total range of baroreflex control of HR (i.e., maximum HR minus minimum HR) or the peak open-loop HR/CSP gains. Our results suggest that 1) it is unlikely that calcium channel antagonists act directly on the baroreceptors or the neural components of the baroreflex loop (i.e., afferent, central and efferent nerves) because they impair CS baroreflex control of MAP but not HR and 2) the impairment of MAP control is predominantly due to a nonspecific blunting of adrenergic vasoconstriction. PMID- 2912600 TI - Duration of ischemia is vital for collateral development: repeated brief coronary artery occlusions in conscious dogs. AB - The effects of two types of repeated transient coronary artery occlusions on collateral development were examined in chronically instrumented, conscious dogs. A 2-minute coronary occlusion at 32-minute intervals (group 1, n = 11) or a 15 second occlusion at 4-minute intervals (group 2, n = 7) were repeated day and night without interruption. In both groups, the total duration of coronary occlusions each day was the same (90 minutes). Before and after repetitive occlusions of either group, effects of transient 2-minute coronary occlusion on regional segment shortening in the ischemic area were examined to assess the functional state of the collateral vessels. In group 1, systolic segment shortening in the area rendered ischemic was reduced to -97.8 +/- 17.7% of the preocclusive control value during 2 minutes of coronary occlusion. After 125-478 repetitive occlusions (3-11 days), the degree of hypokinesia during the 2-minute occlusion was significantly improved to -0.6 +/- 4.6% of the preocclusive value (p less than 0.001 vs. before the repetition). In group 2, it remained unchanged even after 3,500-5,450 repetitive occlusions (11-16 days): -111.8 +/- 8.2% before and -111.4 +/- 13.8% after the repetition of 15-second occlusions (NS). The ratio of peripheral coronary arterial pressure to aortic pressure during transient coronary occlusion, measured by selective catheterization, was significantly higher in group 1 than in group 2 (64.4 +/- 5.3% vs. 20.7 +/- 1.3%, p less than 0.001). These findings suggest that myocardial ischemia of 2 minutes but not 15 seconds is vital to provide effective stimuli for angiogenesis. PMID- 2912602 TI - Writing. PMID- 2912601 TI - Anti-cholinergic effects of quinidine, disopyramide, and procainamide in isolated atrial myocytes: mediation by different molecular mechanisms. AB - Effects of quinidine, disopyramide, and procainamide on the acetylcholine (ACh) induced K+ channel current were examined in single atrial cells, using the tight seal, whole-cell clamp technique. The pipette solution contained guanosine-5' triphosphate (GTP) or guanosine-5'-O-(3-thiotriphosphate) (GTP-gamma S, a nonhydrolysable GTP analogue). In GTP-loaded cells, not only ACh but also adenosine induced a specific K+ channel current via GTP-binding proteins (G) by activating muscarinic ACh or adenosine receptors. Quinidine and disopyramide depressed the ACh-induced K+ current quite effectively. Procainamide had a weak inhibitory effect. Quinidine also depressed adenosine-induced K+ current, while the effect of disopyramide on adenosine-induced current was much smaller than that on ACh-induced current. In GTP-gamma S-loaded cells, the K+ channel was uncoupled from the receptors and was activated irreversibly, probably due to direct activation of G proteins by GTP-gamma S. Quinidine depressed the GTP-gamma S-induced K+ current just as in the cases of ACh- and adenosine-induced currents of GTP-loaded cells. Disopyramide had only a weak inhibitory effect and procainamide showed no effect. From these results, it is strongly suggested that the major mechanisms underlying the anti-cholinergic effects of quinidine, disopyramide, and procainamide are different; quinidine may inhibit the muscarinic K+ channel itself and/or G proteins, while disopyramide and high doses of procainamide may mainly block functions of muscarinic ACh receptors in atrial myocytes. PMID- 2912603 TI - The eccentric coronary atherosclerotic plaque: morphologic observations and clinical relevance. AB - Five hundred consecutive coronary artery segments histologically narrowed 76 to 95% in cross-sectional area by atherosclerotic plaque were classified into concentric and eccentric luminal types. Of the 500 segments, 365 (73%) were eccentric and 185 (27%) were concentric. Of the eccentric lesions, an arc of disease-free wall accounted for 2.3 to 32% (mean 16.6%) of the circumference of the internal elastic membrane. The average thickness of the coronary artery media was thinner in diseased segments (mean 88.4 micron) compared to disease-free wall segments in the same vessel (mean 202.9 micron). The presence of disease-free wall segments has clinical importance in at least three areas: (1) the accuracy with which angiography reflects the morphologic features of the diseased vessel, (2) coronary artery spasm, and (3) the mechanism of coronary balloon angioplasty and subsequent "restenosis" of previously dilated vessels. PMID- 2912604 TI - Echocardiographic monitoring of mental stress test in ischemic heart disease. AB - Mental stress testing can induce ischemia in coronary patients, but often may not induce chest pain and/or electrocardiographic changes. Therefore, we tested the utility of echocardiography to increase the sensitivity of the method. For this purpose, 56 patients undertook arithmetic mental stress tests and then were subjected to coronary angiography. During the test we evaluated left ventricular function, electrocardiography results, and emotional involvement measured by STAI (State Trait Anxiety Inventory). Echocardiography was positive in 21 patients, and electrocardiogram only in 2 patients. No patient complained of chest pain. The remaining 35 patients were negative. Comparing echo data with coronary angiography, in all the cases, sensitivity was 73.5%, specificity 93.3%. Analysis of the STAI revealed that the negative test we observed could be due to a low stressor efficacy. In conclusion, echocardiography in mental stress testing permits improved sensitivity, with loss of specificity in comparison with conventional electrocardiographic monitoring. PMID- 2912605 TI - A new device for balloon inflation during valvuloplasty: a preliminary report. AB - A new device using a lever concept has been designed to facilitate rapid inflation and deflation of balloons during valvuloplasty. This report summarizes and illustrates the design features of the balloon inflation device as well as in vitro results of testing of times for balloon inflation, deflation, and bursting. PMID- 2912606 TI - Lymphocyte subsets in acute rheumatic fever and rheumatic heart disease. AB - Lymphocyte subsets in 53 patients with acute rheumatic fever and 78 patients with chronic rheumatic heart disease were compared with 20 normal control subjects and 39 patients suffering from uncomplicated streptococcal pharyngitis to obtain information about the pathogenesis of the disease. Twenty patients with rheumatic fever were followed for 24 weeks to evaluate changes occurring over the course of the disease. Total leukocyte and lymphocyte counts were increased in patients with rheumatic fever and to a lesser extent in those with rheumatic heart disease, when compared with controls. The difference between the two groups was significant. Patients with acute rheumatic fever had an increased number of B cells and a smaller increase in total T and T-helper-inducer (CD-4) cells. The proportion of B cells increased, while that of T-suppressor-cytotoxic (CD-8) cells fell. An increased number and proportion of B cells was also seen in patients with rheumatic heart disease. Total T and T-helper lymphocyte percentages and numbers were significantly higher in patients with rheumatic fever compared with those of patients with rheumatic heart disease. Follow-up studies at 6, 12, and 24 weeks revealed no significant differences from the entry point studies, although there was a trend toward reduction in the degree of derangement from normal values. Patients with uncomplicated streptococcal pharyngitis, however, did not show perturbations in the T-cell and T-subset counts. Our study suggests that the immunoregulatory defect in acute rheumatic fever is characterized by a relative reduction of suppressor T cells with an absolute increase in helper T cells and B cells, resulting in an increased cellular as well as humoral immune response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2912607 TI - EKG screening program for school athletes. AB - Hypertrophic cardiomyopathy is the most common cardiovascular cause of sudden death in adolescent athletes. The electrocardiogram is abnormal in more than 90% of these individuals. An EKG screening program was developed in order to ascertain the role of the electrocardiogram in identifying athletes at risk for sudden death. A training program was created to instruct school nurses on how to perform electrocardiograms. A questionnaire/consent form was sent to the parents of the athletes. This form asked basic questions concerning the child's past medical history and family history. The electrocardiograms were interpreted by staff pediatric cardiologists. A total of 1,424 students, ages 13 to 18, had 12 lead electrocardiograms performed. In 88.8% the electrocardiogram was normal and the health screening questionnaire revealed no abnormalities in family or personal medical history. In 6.5% of the students, the family history or screening blood pressure recording justified further evaluation. In 72 students abnormalities on the electrocardiogram were noted (5.1%). There were 87 abnormalities noted in the 72 students. Conduction disturbances and arrhythmias were the most common abnormalities noted. In 12 students evidence of ventricular hypertrophy was found. Echocardiograms and stress tests were normal in these individuals. No student was found to have hypertrophic myopathy and no student was restricted from participating in competitive athletic activities. Despite the apparent negative results of this program there were benefits of the screening project. The program resulted in a closer working relationship between school health officials and a major health care facility.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2912608 TI - Hyperthyroid-induced atrial flutter-fibrillation with profound sinoatrial nodal pauses due to small doses of digoxin, verapamil, and propranolol. AB - Atrial fibrillation due to hyperthyroidism is characterized by a rapid ventricular response which is typically resistant to digoxin therapy. We report a patient with atrial flutter-fibrillation who developed cyclic sinus node dysfunction with profound ventricular pauses in response to small doses of digoxin, verapamil, and propranolol, which resolved with discontinuation of the medications. Caution is necessary to avoid paradoxical ventricular slowing when treating hyperthyroid-induced atrial fibrillation. PMID- 2912609 TI - Myxomatous mitral valve degeneration complicating asymptomatic cor triatriatum. AB - Cor triatriatum presenting in adulthood is extremely rare. This paper reports a case of cor triatriatum initially masquerading as mitral stenosis, which was later complicated by myxomatous mitral valve degeneration with severe regurgitation, which necessitated mitral valvular replacement. To the authors' knowledge, such a combination has not been reported in the literature. PMID- 2912610 TI - Imaging of degenerative disease of the cervical spine. AB - The introduction of new techniques to the magnetic resonance imaging (MRI) armamentarium is beginning to provide an MRI examination that overcomes many of the disadvantages noted in earlier reports. An analysis of the various advantages and disadvantages of MRI, plain film myelography, and computed tomographic myelography points to a potential revision of the sequence of diagnostic studies and the workup of cervical degenerative disease. MRI might now be the appropriate first test for the evaluation of the cervical spine in a patient with symptoms referable to degenerative disease when therapeutic intervention is considered. An initial T1-weighted sagittal image with a 3-mm slice thickness will provide excellent contrast evaluation of the vertebral body marrow, disc space height, neural canal, and spinal cord. Disc herniation, canal stenosis, subluxation, and malalignment can be appreciated. Next, a fast, variable flip angle, gradient-echo sequence can be performed to increase the signal density of the cerebrospinal fluid relative to the extradural elements and cord. This provides an increased conspicuousness of extradural disease. Axial gradient-echo fast sequences, with low flip angles, will provide a second orthogonal plane with increased conspicuousness of extradural changes relative to the neural foramen and thecal sac. If necessary, additional oblique views through the neural foramen can be obtained. Finally, if intramedullary disease is considered in the differential, a gated, refocused, T2-weighted examination in the sagittal plane will provide the necessary soft-tissue contrast to detect pathology without unwanted artifact. Thus, unlike plain film or computed tomographic myelography, an examination of the entire cervical region including the osseous structures, extradural cerebrospinal fluid interface, and the spinal cord can be obtained with a single modality in an outpatient setting and in a noninvasive fashion. MRI can certainly replace plain film myelography for the overwhelming majority of situations. If surface-coil MRI fails to demonstrate an abnormality responsible for the patient's clinical symptoms, then a high-resolution computed tomographic scan with or without intrathecal contrast can be obtained. While the cost at first may seem prohibitive, the additional information that MRI is capable of providing in a noninvasive outpatient setting more than compensates for the expense. PMID- 2912611 TI - The halo skeletal fixator. Principles of application and maintenance. AB - The halo skeletal fixator, originally developed for use in patients with poliomyelitis, is now widely used with many types of cervical spine instabilities. Despite its demonstrated effectiveness, certain problem areas, including pin loosening and infection, have been identified. These problems have subsequently inspired detailed studies of skull osteology, biomechanics of pin fixation, and comparisons of techniques of application. Based on these studies, specific recommendations concerning the application and maintenance of the halo have developed. Anterior pin sites should be located in the safe zone approximately 1 cm superior to the orbital rim, cephalad to the lateral two thirds of the orbit, and below the greatest circumference of the skull. The optimal posterior pin sites are located posterolaterally, diagonal to the corresponding contralateral anterior pins. Pins should be inserted perpendicular to the skull, tightened to eight inch/pounds (0.90 Newton-meter), and retightened once at 48 hours. A subsequent loose pin may be retightened once to eight inch/pounds if resistance is met; otherwise, it should be removed and a new one placed in a different location. Infected pins require antibiotic therapy, wound care, and possibly pin-site change and wound debridement. PMID- 2912612 TI - Vertical settling in rheumatoid arthritis. Diagnostic value of the Ranawat and Redlund-Johnell methods. AB - The usefulness of the recently developed Ranawat and Redlund-Johnell craniometric methods was compared with that of the conventional McGregor method for diagnosing vertical settling (VS) of the skull and the atlas on the axis in 209 patients with rheumatoid arthritis (RA). Statistical analysis of the values obtained from roentgenograms revealed close correlations among the three methods. The first two methods were superior to the McGregor method because the measuring points could be identified on plain roentgenograms of the cervical spine in virtually all cases. The McGregor value could not be determined in 38 (18%) patients. Since medullary compression could be detected by magnetic resonance imaging in all patients who showed abnormal Redlund-Johnell values, the Redlund-Johnell method may be useful for diagnosing advanced VS. It also detects not only atlantoaxial lesions but also atlantooccipital lesions. Thus, the Redlund-Johnell method appears to be the best method for diagnosing VS in RA patients. PMID- 2912613 TI - Occipitoatlantoaxial fusion utilizing a rectangular rod. AB - Atlantoaxial subluxation has been treated conventionally by Gallie posterior fusion. This technique, however, has disadvantages such as the frequent occurrence of pseudarthrosis, a high probability of relapse, and the necessity of long-standing strict external fixation until bone fusion. To overcome these problems, posterior occipitoatlantoaxial fusion was performed using a rectangular rod that assures strong internal fixation in 16 patients with atlantoaxial subluxation. The condition was complicated by superior migration of the dens in five patients. Clinical and roentgenographic examinations before and after the operation showed improvements in neurological symptoms and in pain in the neck and occipital region in all patients. Bone fusion was observed in all patients and reduction, performed to the extent possible during the operation, was retained adequately. The present method, which provides strong internal fixation, allows bone fusion and early initiation of rehabilitation with a simple external support of the neck. It also facilitates laminectomy of C1 in patients with associated myelopathy. This procedure, therefore, is particularly effective in patients with marked instability or with rheumatoid arthritis and makes postoperative application of a halo vest or skull traction unnecessary. PMID- 2912614 TI - The effect of collar and distal stem fixation on micromotion of the femoral stem in uncemented total hip arthroplasty. AB - Collar seating and tight distal stem fit were evaluated for their effects on micromotion of the implant in the proximal femur. Collared and collarless implants were inserted with a cementless technique in 42 preserved femoral specimens from adult cadavers and cyclically axially loaded in a 9 degree valgus position. Micromotion was registered with dial indicators. Micromotion was minimized distally and proximally by achieving tight distal fixation. Collar seating prevented distal migration and failure of fixation, but it did not have a detectable effect on mediolateral or anteroposterior proximal micromotion. Toggle appears to be controlled primarily by the distal portion of the stem. Axial load transfer appears to be primarily controlled by collar seating. The least micromotion was achieved with a tight fit distally. PMID- 2912615 TI - The treatment of pigmented villonodular synovitis of the hip. A case report and literature review. AB - Pigmented villonodular synovitis (PVS) is a rare occurrence in the hip joint. A 33-year-old female with PVS of the right hip was successfully treated by synovectomy and total hip arthroplasty. The literature includes 64 cases of PVS involving the hip, with an average patient age of 34.8 years. Multiple methods of initial treatment were encountered including synovectomy alone, synovectomy and total hip arthroplasty, radiation therapy, and arthrodesis. Synovectomy is only effective when articular cartilage is preserved. Total hip arthroplasty, although of concern in such a young population, appears to be the procedure of choice for either advanced cases of PVS or those that have failed joint-sparing procedures. PMID- 2912616 TI - Medial unicompartmental arthroplasty of the knee. Use of the L-cut and comparison with the tibial inset method. AB - Forty-four medial unicompartmental arthroplasties were performed between August 1982 and August 1985 using the L-cut resection and guides. These were compared with 19 medial unicompartmental arthroplasties performed between September 1974 and August 1982 in which the tibial plateau was prepared by the conventional tibial inset method. The L-cut was more precise due to the use of guides. This method allowed the tibial component to be seated directly on the cortical rim of the medial proximal tibial plateau for better support. There was a direct relationship between the placement of the tibial component and the clinical results. In both groups, those patients approaching a tibial prosthesis placement of 90 degrees in the coronal plane and 80 degrees in the sagittal plane had the best clinical results. PMID- 2912617 TI - Load transfer characteristics of a noncemented total knee arthroplasty. AB - This study evaluated load transfer characteristics of femoral and tibial components of a total knee prosthesis that was designed to achieve distal femoral and proximal tibial compressive load-bearing. Strain gauge readings were highest on the cortex of the tibial metaphyseal flare. Roentgenograms of 110 patients with noncemented total knee arthroplasty (TKA) with follow-up periods of 12-24 months were evaluated. Cancellous bone hypertrophy bridging from the undersurface of the tibial component to the metaphyseal cortical bone was noted on all roentgenograms at six months, suggesting stress transfer through cancellous bone to this area. Anterolateral sinking was noted in six of the first 46 patients but was not seen again in the series after a design change was made to more rigidly fix the stem in the bone of the upper tibia. Roentgenograms of the femoral components demonstrated distal bone hypertrophy suggesting compressive load bearing. None of the femoral components migrated or sank. PMID- 2912618 TI - Porous-coated knee arthroplasty. A case report concerning bone ingrowth. AB - The area of bone-metal interaction in uncemented implants is regarded by many investigators as the key to the success or failure of the implant. The nature of the interaction is poorly understood because the zone is technically difficult to visualize and analyze. In order to test the power of modern imaging, analyzing, and metallurgical methods in this context, a well-functioning porous-coated knee prosthesis (tibial component) removed from the knee of a 65-year-old man was sectioned and examined by light microscopy, roentgenogram, scanning electron microscopy, and radiologic energy dispersive analysis. Independently, these methods demonstrated that the prosthesis was held in situ by collagenous tissue between and below the metal pellets of the prosthesis. Calcified bone did not appear to interact with the prosthesis and is probably not a major factor for prosthesis fixation. The various analytic methods described are suitable and sufficient for further exploration on a larger scale of the zone of bone-metal contact in cementless implants. PMID- 2912619 TI - Gait analysis in patients with gonarthrosis treated by high tibial osteotomy. AB - The basic parameters of gait were studied in 14 patients with medial gonarthrosis before and eight to 12 months after high tibial osteotomy. In seven patients, the osteotomy was fixed with staples. The patient was placed in plaster immobilization for six weeks and weight bearing was allowed after ten weeks. In the other seven patients, the osteotomy was fixed with a T-plate, and immediate joint motion and weight bearing were allowed after six weeks. There was no difference in any parameter of gait among patients treated with the two techniques. For all patients, the mean maximal velocity preoperatively was 65% of that of normal people, with only a slight, nonsignificant increase at the follow up examination. An additional indication of insufficient rehabilitation was the decrease in stride length at constant maximal velocity at the follow-up evaluation. Positive correlations were found between stride length and muscle torque in the thigh. Positive correlations were also found between a subjective score and maximal velocity. Simple tests of velocity, stride length, and stride frequency are recommended as an easy and decisive method of follow-up evaluation. PMID- 2912620 TI - Care of the multiply injured patient with cervical spine injury. AB - Cervical spine injuries can be disastrous. The treatment begins at the accident scene by obtaining an appropriate history, physical examination, and evaluation of the mechanics of the accident. Emergency medical stabilization takes precedence, but the cervical spine should be stabilized until an injury in this area is ruled out. If the patient has suffered a head injury or is violent, cervical spine precautions should be maintained until spinal column injuries have been ruled out roentgenographically. Because of the complexities of the evaluation and treatment of cervical spine injury in the multiply injured patient, an algorithm to assist in the management and evaluation of the patient has been developed, and a multidisciplinary, specialized evaluation and treatment team is employed. Through this approach, mortality in the multiply injured patient with a cervical spine injury has been reduced to 22%. Of 58 patients with cervical spine injuries evaluated by this aggressive approach, 14 patients had associated spine fractures, and 9 patients had positive peritoneal lavage requiring surgical exploration. Injuries involving other organ systems were also diagnosed and treated. Formal, rigid evaluation plans and aggressive multidisciplinary treatment are useful in saving the lives and salvaging neurologic function of these patients. PMID- 2912621 TI - The relationship of stride characteristics to pain before and after total knee arthroplasty. AB - The relationship between the changes in stride characteristics and the changes in pain that occurred before and after total knee arthroplasty (TKA) were examined in 18 patients with a diagnosis of osteoarthritis. The patients were observed after either bilateral or unilateral TKA. Measurements of stride characteristics by footswitch analysis and assessments of pain by visual analog scale were performed preoperatively and at five months and at 13 months postoperatively. Stride characteristics improved and pain diminished after surgery. Improvements, from preoperative to five months postoperative, were noted in seven of eight stride characteristics. The improvements in velocity and stride length were related to the decreases in pain over that period. Improvements from five months to 13 months postoperative were independent of the decrease in pain over that period and independent of the increase in active knee flexion angle. When evaluating stride characteristics after TKA, it is necessary to consider the effect of pain relief and to monitor the patient's ambulatory progress after pain diminishes. PMID- 2912622 TI - Tibialis posterior tendon dysfunction. AB - Dysfunction of the tibialis posterior tendon evolves through a series of stages. The pain symptoms, clinical signs, and roentgenographic changes for each of these stages are characteristic. This staging system permits clarification and individualization of dysfunction, expected pathologic changes, and surgical treatment. The importance of the tibialis posterior tendon in normal hindfoot function and its treatment when injured are now being properly appreciated. PMID- 2912623 TI - The treatment of cervical spine disorders. PMID- 2912624 TI - A long-term follow-up study of tibiotalar dislocations without associated fractures. AB - A retrospective review of 19 cases of pure tibiotalar dislocation without associated fractures showed that most patients with closed injuries will have a good long-term result. Closed injuries generally have functionally insignificant instability, loss of motion, and no roentgenographic evidence of degenerative changes. The long-term results were worse in open dislocations that had a high incidence of concurrent neurovascular injury. These neurovascular injuries were of minimal functional significance. The role of primary ligament repair is difficult to delineate. PMID- 2912625 TI - Stress fracture of the lateral metatarsals following double-stem silicone implant arthroplasty of the hallux metatarsophalangeal joint. AB - Stress fractures of the lateral metatarsal bones occur frequently and are most commonly seen following repetitive trauma. However, such fractures rarely occur after reconstructive operations involving the hallux metatarsophalangeal joint. The authors report four patients who developed a lateral metatarsal stress fracture during the first year following use of a double-stem silicone implant to reconstruct the hallux and, in addition in the case of one patient, the second metatarsophalangeal joint. An analysis of all these patients established the incidence of this complication to be 3%. The etiology of these fractures appears to be an overloading of the lateral metatarsals secondary to some shortening of the hallux metatarsal or in reestablishing motion to the hallux metatarsophalangeal joint. All fractures healed without complication and did not result in further forefoot symptoms or deformities. However, this complication should be suspected when lateral metatarsalgia develops following silicone implant arthroplasty because roentgenograms initially may be normal. PMID- 2912626 TI - The lateral approach compared with the volar approach for exposure of the hook of the hamate. AB - Two cases of delayed union of the hook of the hamate were satisfactorily treated by excisional surgery. The volar surgical approach through the palm is common, but to expose the hook some hypothenar muscles and cardinal ligaments must be divided. Care must be taken to avoid injury of the motor and sensory branches of the ulnar nerve that occur close to the hook. The lateral approach between the abductor digiti minimi muscle and the fifth metacarpal bone is easier and less traumatic. This approach is also safer for the ulnar neurovascular bundle, which is protected by volar retraction and the hypothenar muscles. The lateral approach is advantageous unless the injury is complicated by ulnar nerve palsy or flexor tendon injury. PMID- 2912627 TI - The effect of the CAT-CAM above-knee prosthesis on functional rehabilitation. AB - Five, rehabilitated, unilateral above-knee amputees (average age, 34.4 years) using quadrilateral sockets were converted to Contoured Adducted Trochanteric Controlled Alignment Method (CAT-CAM) sockets to determine the effect on ambulatory function. Patients were evaluated before and after conversion for subjective acceptance, gait deviations, relative femoral shaft inclination, coronal-plane hip abduction torque, and ambulatory metabolic demands. The CAT-CAM socket was subjectively rated superior by four patients. Most gait deviations improved or disappeared. Femoral shaft inclination angles improved an average of 6.5 degrees toward adduction by roentgenographic measurements in four patients. Film records suggest that the compensatory lateral trunk lean, seen in patients with quadrilateral sockets, diminished after conversion. These four patients increased their customary gait velocities, and all showed a reduction in the quantity of oxygen consumed per meter traveled by up to 50%. PMID- 2912628 TI - The tension-stress effect on the genesis and growth of tissues: Part II. The influence of the rate and frequency of distraction. AB - To assess the influence of both the rate and the frequency of distraction on osteogenesis during limb elongation, a canine tibia was used with various combinations of distraction rates (0.5 mm, 1.0 mm, or 2.0 mm per day) and distraction frequencies (one step per day, four steps per day, 60 steps per day). The distractions were performed after both open osteotomy and closed osteoclasis. Histomorphic and biochemical studies were conducted on the elongated osseous tissue, fascia, skeletal muscle, smooth muscle, blood vessels, nerves, and skin. It was determined that distraction at a rate of 0.5 mm per day often led to premature consolidation of the lengthening bone, while a distraction rate of 2.0 mm per day often resulted in undesirable changes within elongating tissues. A distraction rate of 1.0 mm per day led to the best results. It was also observed that the greater the distraction frequency, the better the outcome. With optimum preservation of periosseous tissues, bone marrow, and blood supply at the time of osteotomy, stability of external fixation, and 1.0 mm per day of distraction in four steps, osteogenesis within the distraction gap of an elongating bone takes place by the formation of a physislike structure, in which new bone forms in parallel columns extending in both directions from a central growth zone. The growth plate that forms under the influence of tension-stress has features of both physeal and intramembranous ossification, yet is neither; instead, the distraction regenerated bone is unique, providing numerous applications in clinical traumatology, orthopedics, and other medical disciplines. PMID- 2912629 TI - The origin of the osteoclast. AB - The origin of the osteoclast remains controversial even though investigations using light microscopy, tissue culture, electron microscopy, microcinematography, autoradiography, parabiosis, quail chick nuclear markers, giant lysosomal markers in beige mice, Y chromosomes, bone marrow cell culture, and monoclonal antibodies have been performed since its discovery. Concepts of the origin of the osteoclast have been changing. The classic concept was that the osteoclast originated from connective tissue cells. Others hypothesized that it originated from mature hematopoietic cells, particularly from monocyte or macrophage cells. A recent concept proposed an origin from hematopoietic stem cells. The hematopoietic stem cell was believed to differentiate into two cell lineages: one of monocytes and the other of preosteoclasts. The authors' concept, based on experimental observations as well as alternate interpretations stemming from experimental reports of other researchers, proposes an origin from local, nonhematopoietic, possibly perivascular mesenchymal cells. However, the relationship of the hematopoietic stem cells to perivascular mesenchymal cells in the periosteum at an early stage of enchondral ossification is still not well known. Therefore, the origin of the osteoclast also remains uncertain. PMID- 2912630 TI - Periosteal bone formation elicited by partially purified bone morphogenetic protein. AB - A small amount of partially purified, water-soluble murine osteosarcoma-derived bone morphogenetic protein (BMP) was implanted into the dorsal muscles of mice in combination with calf skin gelatin or collagen as carriers. Changes in the ribs adjacent to the implants were then chronologically observed. On implantation of BMP with gelatin, the gelatin was rapidly absorbed and no ectopic bone formation was observed, but periosteal cellular proliferation with subsequent formation of periosteal cartilage and bone was seen in ribs adjacent to the implant. Implantation of the same amount of BMP fraction or gelatin alone as controls did not result in either any ectopic bone formation in situ or any periosteal bone formation in adjacent ribs. Implantation of BMP with collagen resulted consistently in both ectopic bone formation in situ and periosteal bone formation in adjacent ribs. These results suggest that BMP is diffusible in vivo and is capable of eliciting a response from periosteum to stimulate periosteal bone formation. PMID- 2912631 TI - Subaxial injuries. AB - Injuries to the subaxial cervical spine must be suspected in any patient who suffers a head injury or complains of neck pain or neurologic symptoms of the arms or legs following an accident, particularly a motor vehicle or diving accident. Careful neurologic examination and lateral roentgenograms are indicated in all patients with suspected injury. If there is any neurologic deficit, fracture, or dislocation seen on roentgenogram, skull-traction tongs should be applied to provide stability and prevent further damage. If the neurologic examination and roentgenograms are normal, a stretch-test roentgenogram may be indicated to detect an occult ligamentous injury. Muscular strains and first degree sprains may be treated with a collar and early active exercise. Subluxation and facet dislocations are most reliably treated with a posterior one level fusion. Comminuted body fractures are best treated with an anterior strut graft. Complex fracture-dislocations of both anterior and posterior columns may be best treated with skull traction followed by combined anterior and posterior stabilization. Halo-jacket immobilization has few indications in subaxial injuries. It does not provide enough stability to maintain reduction of unstable mid- and low-cervical injuries. It may be used for postoperative immobilization in very unstable situations, but its greatest use is in immobilization of C1 and C2 fractures. PMID- 2912633 TI - The primary link in the chain of events in osteoarthrosis is a biochemical failure of the cartilage. PMID- 2912632 TI - Prevalence and coincidence of degenerative changes of the hands and feet in middle age and their relationship to occupational work load, intelligence, and social background. AB - The occurrence and coincidence of degenerative changes in hands and feet were studied in 574 55-year-old residents of Malmo, Sweden. The prevalence of Heberden's nodes and arthrosis of the first carpometacarpal joints (CMC-I) was 15% and 2% higher in women, respectively. Degenerative changes in the feet, again more common in women, occurred in 16%. In men there was a coincidence between degenerative changes in hands and feet. Women with Heberden's nodes had more physically demanding jobs. Otherwise, factors such as intelligence and social background could not be demonstrated to correlate with hand and foot conditions. PMID- 2912634 TI - The halo. A spinal skeletal traction fixation device. By Vernon L. Nickel, Jacquelin Perry, Alice Garrett, and Malcolm Heppenstall, 1968. PMID- 2912635 TI - The quadrangular fragment fracture. Roentgenographic features and treatment protocol. AB - The quadrangular fragment fracture is a clinically discrete type of cervical lesion that poses a difficult management problem. Physically, it resembles the triangular fragment fracture or teardrop fracture, but it responds very poorly to posterior fusion, the conventional treatment for these fractures. It is characterized by a quadrangular-shaped fragment from the anterior one-third of the vertebral body, a significant degree of posterior subluxation, an angular kyphosis, and an increased interspinous space with facet subluxation due to disruption of the soft tissues. Recognition of the quadrangular fragment may help determine the treatment protocol. A group of 23 patients with quadrangular fragment fracture was treated with the standard protocol and had poor results, including difficulty in maintaining reduction, neck pain, and significant residual kyphosis. A second group of 15 patients received kyphosis. A second group of 15 patients received the second treatment protocol, which consisted of one to two weeks of skull traction over an extension bolster, followed by an anterior interbody strut graft to stabilize the fracture and further traction over an extension bolster until four weeks postinjury. Treatment minimized the angular kyphosis apparent at bony healing, and all patients achieved satisfactory union with good alignment and no significant neck pain. PMID- 2912636 TI - Traumatic spondylolisthesis of the axis. AB - Hanging, a common method of execution, began in antiquity and continues to this date. Unfortunately, the exact cause of a victim's demise was not always obvious, and many victims died as the result of asphyxiation from the hangman's noose. In the latter part of the 19th century, scientific curiosity led to autopsy studies of the cervical spine; Paterson in 1890 first described the lethal lesion. Experimental work in 1913 demonstrated that when the hangman's knot was placed beneath the chin, death rapidly occurred because of a traumatic spondylolisthesis of the second cervical vertebra. This knot placement then became standard as the most efficient method of execution. It was not until the mid-20th century that the similarity between judicial and civilian injury was recognized. The reports were infrequent, and most of the pars interarticularis fractures resulted from automobile accidents in which the victim was thrown forward and struck his or her face against the windshield which caused sudden violent hyperextension. The similarity between civilian and vehicular injuries was recognized in 1965 by Schneider who, together with his associates, reported eight cases; it was this group who introduced the term "hangman's fracture". Garber presented his thoughts on this subject, noting that there was a difference between the forces generated by judicial hanging and those caused by motor vehicle accidents and other similar civilian injuries. The former results in axial loading and hyperextension, and, rarely, in flexion or axial loading. Since the lesion occurs at the pars interarticularis of C2, Garber suggested that a more appropriate term might be traumatic spondylolisthesis of the axis. PMID- 2912637 TI - Traumatic lesions of the occipitoatlantoaxial complex. AB - Injuries of the occipitoatlantoaxial complex are relatively rare but form a group of ligamentous and bony lesions that may unnecessarily confuse the clinician. Since fractures of the dens and traumatic spondylolisthesis of the axis have been well described in a number of large series, this article concentrates on the lesions less frequently seen and described. The ligamentous injuries are occipitoatlantal dislocation, rupture of the transverse ligament, and atlantoaxial rotatory fixation. The bony injuries are fractures of the occipital condyles, atlas, and the lateral masses of C2. The incidence, diagnostic criteria, and treatment modalities depend on the nature of localization of the traumatic lesions. PMID- 2912638 TI - Critical care: when is enough enough? PMID- 2912639 TI - Withholding and withdrawing treatments: ethics at the bedside. PMID- 2912640 TI - Surgery of intracranial tumors: aspects of operating room design with integration and use of technical adjuvants. PMID- 2912641 TI - Difficult decisions in managing patients with benign brain tumors. PMID- 2912642 TI - Surgical decision-making for malignant brain tumors. PMID- 2912643 TI - Domains in the neurosciences: a 3-dimensional view of the brain. PMID- 2912644 TI - Commitment and contribution. PMID- 2912645 TI - Malignancy as it affects the patient. PMID- 2912646 TI - The rational use of analgesics in the management of patients with acute and chronic pain. PMID- 2912647 TI - Use and abuse of drug pumps in cancer pain. PMID- 2912648 TI - The status of dorsal root entry zone lesions in 1987. PMID- 2912649 TI - Are randomized clinical trials of surgical procedures feasible? PMID- 2912650 TI - The art and science of evaluating neurosurgical treatment. PMID- 2912651 TI - Alternatives in the surgical treatment of herniated lumbar disks. PMID- 2912652 TI - What are the determinants of a competent neurosurgeon? PMID- 2912653 TI - Risky business: is personal risk an obligation in treating patients? PMID- 2912654 TI - Neurosurgical critical care: who's in charge? PMID- 2912655 TI - The intensive care unit: who's in charge? PMID- 2912656 TI - Subspecialty certification in critical care. PMID- 2912657 TI - ICU management of pulmonary dysfunction in neurosurgical patients. PMID- 2912658 TI - Hyponatremia in neurosurgical patients. AB - Hyponatremia is the most common electrolyte disturbance seen in a neurosurgical ICU. The most common cause is impaired excretion of water, which may be due to many causes. The hyponatremia itself is of importance only because of its effect on ECF osmolality, which, when low, causes cellular swelling and dysfunction. While a low serum sodium is most commonly associated with an increased ECF, it may also be associated with a normal or low ECF. In any of these situations, however, the symptomatology will be the same. On the other hand, the examination of the patient and the laboratory examinations will help in determining whether it is an instance of overhydration or underhydration. The urgency and type of treatment are dictated by the severity of the patient's symptoms. PMID- 2912659 TI - University Hospital reorganization. PMID- 2912660 TI - Cough induced by angiotensin-converting-enzyme inhibitors. PMID- 2912661 TI - FDA announces new procedures to speed drug availability for life-threatening and severely debilitating conditions. PMID- 2912662 TI - FDA approves marketing of octreotide. PMID- 2912663 TI - Comparative dosage and toxicity of heparin sodium in the treatment of patients with pulmonary embolism versus deep-vein thrombosis. PMID- 2912664 TI - Risk of renal dysfunction in critically ill trauma patients receiving aminoglycosides. PMID- 2912665 TI - Computer-simulated effect of errors in infusion duration and blood sampling times on pharmacokinetic calculations for gentamicin. PMID- 2912666 TI - Variability of indocyanine green pharmacokinetics in healthy adults. PMID- 2912667 TI - Effect of source of population data on phenytoin dosage predictions in black patients. PMID- 2912668 TI - Comparative bioavailability of procainamide in capsule versus syrup form. PMID- 2912669 TI - Calculation of heparin dosage in a morbidly obese woman. PMID- 2912670 TI - Rational loop-diuretic combinations. PMID- 2912671 TI - Dermatographism in a horse. AB - An eight-year-old Thoroughbred gelding with dermatographic urticaria is presented. Forelimb edema and generalized urticaria were the presenting clinical signs. All hematologic and serum biochemical values were normal. Immunologic and histologic evaluation failed to reveal specific abnormalities. During hospitalization, an urticarial response to mechanical pressure (dermatographism) was identified. Clinical responses to corticosteroid and antihistaminic (H1) therapy were equivocal. The condition resolved in five weeks and an etiology was not discovered. A discussion of the pathogenesis, diagnosis and treatment of dermatographic urticaria in humans is included with the report. PMID- 2912672 TI - Changes in equine carpal joint synovial fluid in response to the injection of two local anesthetic agents. AB - The effects of repeated arthrocentesis and injection of local anesthetic agents, lidocaine HCl or mepivacaine HCl on the equine middle carpal joint were investigated. Synovial fluid samples were evaluated before, and 12, 24 and 48 hours following, treatment. The greatest changes from pretreatment values occurred in synovial fluid cellularity. Repeated arthrocentesis caused a moderate increase in cell counts, while injection of local anesthetics caused a greater increase. Alterations in mucin clot quality, hyaluronic acid content, fluid viscosity, total protein and immunoglobulin G were generally of no significance. The most sensitive sampling time to detect changes caused by a given treatment was 24 hours following treatment while the 12 hour sampling period appeared to be the best at detecting differences between treatments. Repeated arthrocentesis has a definite effect on synovial fluid composition but the effects appear to decrease with repeated centesis. Lidocaine HCl and mepivacaine HCl are irritating to the synovial environment. Clear differences between responses to the drugs could not be identified. PMID- 2912673 TI - Pine needle abortion in cattle: associated changes in serum cortisol, estradiol and progesterone. AB - Nineteen spring-calving cows were used in an experiment to study the effect of feeding pine needles on incidence of premature parturitions (abortions) and the associated changes in serum cortisol, estradiol-17 beta and progesterone. The study was conducted over 2 years (1983, seven cows fed pine needles and three controls; 1984, six cows fed pine needles and three controls). Experimental feeding started at an average of 250 d of gestation and continued until parturition. Daily blood samples were taken from the start of feeding through 2 to 4 d after parturition. Feeding pine needles shortened gestation by 16 d and induced a premature normal rise in cortisol and estradiol-17 beta associated with parturition. Cortisol concentrations were also high at the beginning of the bleeding period and remained higher in pine needle-fed cows. An abrupt rise in progesterone concentration occurred after the start of pine needle feeding which then decreased sharply for 7 to 8 d before parturition and did not decrease to control concentrations until after parturition. We conclude that feeding pine needles to pregnant cows in late gestation causes abortions and that these abortions are directly caused by or are associated with changes in steroid metabolism. PMID- 2912674 TI - Pine needle abortion in cattle: pathological observations. AB - Grazing of ponderosa pine needles by pregnant cows may cause abortion. The abortions are frequently accompanied by retained placenta. Death is not uncommon in cows that abort. Ten cows were placed on a ponderosa pine needle experiment. Six of these cows were fed pine needles and four served as controls. All six cows receiving pine needles aborted, and three of them died shortly after the abortion. Death was due to a severe septicemia. Although the cows were necropsied shortly after death, all tissues were necrotic. Other lesions are described. Three of the six calves died shortly after the abortion. The other three were small and weak but survived due to intensive care. PMID- 2912675 TI - Evaluation of a digitonin disk assay to discriminate between acholeplasma and mycoplasma isolates from bovine milk. AB - A study was undertaken to evaluate effectiveness of a digitonin disk inhibition test to discriminate between Acholeplasma laidlawii and Mycoplasma sp. isolated from bovine milk. The test measured zone diameters of growth inhibition surrounding a digitonin-containing disk on solid medium. Zones of inhibition for 20 isolates of A. laidlawii, ranging from 8-14 mm, did not overlap those of 261 isolates of Mycoplasma sp., ranging from 16 to 38 mm. Examination of variation in zone diameters for M. bovis found that inhibition was not appreciably affected by agar dehydration. Zones of inhibition increased with increasing dilutions of stock culture and decreased with increasing incubation time. Analysis of variance and Fisher's least significant difference test of logn zone diameters revealed that differences in mean logn zone diameters were different at the 0.01 level of significance between some of the six species of mycoplasma examined, indicating that growth among some species of mycoplasma was effected differently by digitonin. The digitonin test was found to clearly discriminate between A. laidlawii and Mycoplasma sp. indicating that the test would be useful as a practical screening test of individual-cow and bulk tank milk for mycoplasmas. PMID- 2912676 TI - Ileal impaction in the horse: 75 cases. AB - Records of 75 horses with ileal impactions were examined retrospectively. There was a sex predilection towards mares. Arabians were over-represented compared to the hospital population. The average age was 8.3 years. Abdominal pain was observed in 96% of horses. Nasogastric reflux was present in 56% of horses, small intestinal distention was found on rectal palpation in 96% and an ileal impaction in 25%. Exploratory celiotomy was performed in 69 horses, the mass was reduced by extramural massage in 67 horses, and ingesta was removed via enterotomy in 2. Jejunocecostomies were performed in 47 horses. Twenty-five horses developed postoperative ileus, and 11 developed laminitis. Twenty-seven horses survived. Significant differences (p less than 0.05) between survivors and non-survivors were found for rectal temperature (37.7 and 38.2 degrees C, respectively), plasma protein concentration (7.8 and 8.9 g/dl, respectively) and anion gap (15 and 21.3 mEq/l, respectively). Survival decreased with increasing duration of clinical signs. Enterotomy, enterectomy, and/or jejunocecostomy performed during surgery had a deleterious effect on survival. PMID- 2912677 TI - [Agranulocytosis in primary biliary cirrhosis]. PMID- 2912678 TI - [Is there a specific therapy for primary glomerulonephritis?]. PMID- 2912679 TI - [Brain abscess. Prognostic factors]. AB - Thirty-eight cases of cerebral abscess were analysed retrospectively for any factors that might influence outcome. Using the "Glasgow outcome score", age, history, level of consciousness, as well as various computed tomography findings (cisternal swelling, compression of the ventricular system, degree of oedema and size of abscess) were considered for their prognostic value. It was found that age over 40 years and clouded consciousness exerted a statistically significant unfavourable effect (P less than 0.05). Outcome was also unfavourable in half the patients with multiple abscesses, but the number of cases (six) was too small to be statistically significant. All other variables had no statistically significant influence on prognosis. PMID- 2912680 TI - [Exacerbation of psoriasis during alpha-interferon therapy]. AB - In three female patients with metastasising malignant melanoma psoriasis exacerbated during the third week of treatment with recombinant interferon-alpha 2b, at a weekly dosage of three times 10 million IU. The psoriatic lesions vanished almost completely after discontinuing the drug and systemic administration of corticosteroids. It appears that induction of psoriasis exacerbation is yet another important side effect of interferon, at least at elevated doses, whereas low alpha-interferon dosage levels may improve psoriasis in nononcological patients. PMID- 2912681 TI - [Proarrhythmic effect of ajmaline in idiopathic ventricular tachycardia]. AB - A 23-year-old woman was hospitalized because of life-threatening monomorphic ventricular tachycardia (VT) of 150 beats/min. An intravenous bolus of lidocaine was without effect but 25 mg ajmaline converted the tachycardia to sinus rhythm. A total of 70 mg ajmaline was subsequently infused because of frequent ventricular premature systoles. During this treatment polymorphic VT with very wide QRS complexes developed, but spontaneously disappeared after ajmaline had been discontinued. The case demonstrates the need for taking into account the potential risk of a proarrhythmic effect of anti-arrhythmic drugs. PMID- 2912682 TI - 3,5,3'-Triiodothyronine determines the viability of GC cells after heat shock. AB - The heat shock (HS) response is a characteristic disruption of protein synthesis which occurs in cells exposed to a variety of noxious stimuli. The effects of HS on thyroid hormone-responsive GC cells were studied in an attempt to devise an in vitro model for the adaptive changes in thyroid hormone action caused by nonthyroidal disease. HS enhanced GC cell synthesis of 70 K and 90 K proteins in a manner previously described as characteristic of the HS response in many tissues. A step-wise decrease in GC cell viability occurred when cells were exposed to 45 C for 10 to 35 min. HS (45 C, 20 min) resulted in a rapid decrease in binding of T3 to nuclear receptors. Two hours after HS, analysis of T3 binding to isolated nuclei showed a 50% fall in binding capacity (240 fmol/100 micrograms DNA) compared to non-HS control cells (540 fmol/100 micrograms DNA); no difference in dissociation constant (Kd) was observed. The effect of thyroid hormone on cell viability after HS was then determined. Thyroid hormone depletion (less than or equal to 0.02 nM T3) resulted in significantly (P less than 0.05) enhanced cell viability compared to cells cultured with physiological T3 (0.2 nM) after incubation at 45 C for intervals of 10-35 min. This inverse relationship between medium T3 content and cell tolerance of HS occurred over a wide range of T3 concentrations. Mean cell viability after exposure to 45 C for 20 min was 44 +/- 3% in T3-depleted cultures (less than or equal to 0.02 nM), 27 +/- 1% to 32 +/- 5% in cultures containing 0.07-0.5 nM T3, and 13 +/- 3% in cultures containing 5 nM T3. Our results thus characterize the response to HS in GC cells and the relationship of this response to medium T3. Similar to the effect of various nonthyroidal diseases on rat hepatocytes in vivo, HS resulted in a decrease in T3 nuclear receptors. Similar to the adverse effect of thyroid hormone on morbidity in animals with experimental diseases or injury, GC cell viability after HS was inversely related to medium T3 content. Thus the HS response in GC cells may be a valuable in vitro model relevant to the effect on thyroid hormone action caused by nonthyroidal disease. PMID- 2912683 TI - Interaction of rat liver glucocorticoid receptor with histones. AB - The activated glucocorticoid-receptor complexes (GRC) from rat liver bind tightly to histone (from calf thymus)-agarose and cannot be eluted with 3 M KCl or 50% ethylene glycol, but can be eluted with 20 mM pyridoxal 5'-phosphate (PALP). Purified activated GRC were found to have much higher affinity for histones H3 and H4 (arginine-rich histones) than for histones H2A and H2B (slightly lysine rich histones) and to have negligible affinity for histone H1 (lysine-rich histone). The GRC bound to immobilized histones could be eluted with PALP, but not with its related compounds, such as pyridoxamine, pyridoxamine 5'-phosphate, pyridoxal, and pyridoxine, suggesting a specific effect of PALP. Not only activated GRC but also unactivated GRC were found to bind to immobilized histones. However, from their profiles of elution from a histone-agarose column by 20 mM PALP, the activated GRC seemed to have higher affinity than unactivated GRC for histone. Our results suggest that the binding of GRC to histones could be associated with a mechanism for alteration of the chromosome structure by the hormonal signals, before the binding of the GRC to a specific sequence of DNA in regulatory elements of glucocorticoid-responsible genes. PMID- 2912684 TI - Subcellular localization of prolactin in the anterior pituitary cells of the female Japanese house bat, Pipistrellus abramus. AB - We investigated the subcellular localization of PRL and GH in the pituitary gland of the female Japanese house bat by the double immunolabeling procedure using the protein A-gold method combined with electron microscopy and demonstrated a seasonal alteration in the distribution of PRL within the cells. The seasonal changes were related to the different phases of the bats' reproductive cycles. Mammosomatotrophs (MS cells) containing both PRL and GH were constantly present throughout the reproductive cycles of the female bats and they were remarkably hypertrophied during pregnancy. The distribution pattern of PRL and GH within the MS cells was extremely variable owing to the different phases of reproductive cycles of the bats. We divided MS cells into the following four types: the cell containing 1) only mixed granules containing both PRL and GH, 2) both mixed and PRL granules, 3) mixed, PRL and GH granules, 4) both mixed and GH granules. While pure PRL-containing cells were observed in pregnant and lactating bats, they were not observed in bats obtained during prehibernation, midhibernation, and arousal periods. These results suggest that MS cells in the female bats hypertrophy during pregnancy and that some of them may be transformed into PRL-producing cells. PMID- 2912685 TI - Vasoactive intestinal peptide in the anterior pituitary is increased in hypothyroidism. AB - Vasoactive intestinal peptide (VIP) and PRL have been reported to be colocalized in rat lactotropes. To determine whether induced hypothyroidism, known to reduce pituitary PRL concentration, also reduces pituitary concentration of VIP, rats were treated with antithyroid drugs for 3 weeks. Pituitary PRL concentration in male rats (micrograms/mg protein) was markedly reduced by this treatment (9.4 +/- 1.0 vs. 2.3 +/- 0.4 when extracted at pH 1.1, 17.9 +/- 3.0 vs. 3.4 + 0.4 when extracted at pH 7.4, 21.8 +/- 3.3 vs. 6.7 + 1.3 when extracted at pH 10.0). Contrary to expectation, pituitary VIP concentration was markedly increased in hypothyroidism; in males from 169.5 +/- 20.3 to 834.0 +/- 82.2 pg/mg protein, and in females (whose pituitary PRL had been similarly reduced) from 103.1/I +/- 34.1 to 771.6 +/- 100.9 pg/mg protein. Serum PRL was significantly reduced in hypothyroid males (7.4 +/- 1.6 vs. 28.9 +/- 12.2 ng/ml) whereas in females, serum PRL was not significantly altered (41.4 +/- 11.6 vs. 38.8 +/- 14.3 ng/ml). The effect of hypothyroidism was reversed by administration of T4 in physiological doses. The authenticity of pituitary immunoreactive VIP was further established by demonstrating chromatographic patterns by Sephadex G-50 gel exclusion and reverse phase HPLC separations identical to synthetic VIP. Immunohistochemically reactive VIP cells could not be demonstrated in normal pituitaries, but the marked increase in VIP in hypothyroid animals made it possible to visualize a population of VIP immunoreactive stellate cells which appear to be distinct from hypothyroid lactotropes and thyrotropes. PMID- 2912686 TI - Perturbation of intracellular calcium ion concentration in single rat granulosa cells by angiotensin II. AB - A physiological role of angiotensin II (Ang II) on the ovary has been suggested recently, but the mechanism of action is not understood. In 18 out of 44 individual rat granulosa cells loaded with fura-2, Ang II caused a rapid and transient increase in intracellular free calcium ion concentration, [Ca2+]i. In 12 of these cells, 10(-5) M Ang II caused a 3.7 +/- 0.5-fold increase in [Ca2+]i. After 74 +/- 4 sec, [Ca2+]i returned to the resting levels (96.0 +/- 3.7 nM). Angiotensin I was without effect (n = 9). The effect of Ang II on [Ca2+]i changes could be completely blocked by a potent long-acting Ang II antagonist, [Sar1, Thr8]-angiotensin II, suggesting a receptor-mediated mechanism. The present results strongly indicate that rapid alterations in [Ca2+]i is an early step in the signal transduction of Ang II in a subpopulation of cells in the rat ovary. PMID- 2912687 TI - Human parathyroid hormone carboxyterminal peptide (53-84) stimulates alkaline phosphatase activity in dexamethasone-treated rat osteosarcoma cells in vitro. AB - Previous studies in our laboratory have demonstrated relatively large numbers of cell surface binding sites for the carboxylterminal (53-84) region of PTH on ROS 17/2.8 rat osteosarcoma cells, a clonal osteoblast-like cell line. In order to gain insight into the significance of these carboxylterminal binding sites, we studied the effect of intact bovine PTH (1-84), its aminoterminal fragment bovine PTH (1-34), and the human PTH carboxylterminal fragment (53-84) on alkaline phosphatase activity in dexamethasone-treated rat osteosarcoma (ROS) 17/2.8 cells. While bovine PTH (1-84) and its aminoterminal 1-34 fragment inhibited alkaline phosphatase activity, we saw a dose-related stimulation of activity by human PTH (53-84), with maximal stimulation occurring after 120 hours, at a concentration of 10(-8) M. The effect was not seen in dexamethasone-untreated cells. To our knowledge, this is the first published demonstration of biological activity of this carboxylterminal PTH peptide, previously thought to be inactive. It is likely that dexamethasone caused differentiation of cells to a type more sensitive to human PTH (53-84). Further studies are necessary to elucidate the physiological significance of these findings. PMID- 2912688 TI - Regulation of blood flow to the rabbit corpus luteum: effects of estradiol and human chorionic gonadotropin. AB - We tested the hypothesis that estrogen and hCG can modify blood flow in the rabbit corpus luteum. Radioactively labeled microspheres were used to measure luteal blood flow in pseudopregnant rabbits in which estrogen had been withdrawn to initiate premature luteal regression and in pseudopregnant rabbits injected with hCG. Removal of estradiol-filled Silastic capsules on day 10 of pseudopregnancy caused an 80% decrease in the serum progesterone concentration within 24 h. Despite the decline in progesterone secretion, luteal blood flow remained at very high levels and was not different from that in control rabbits treated continuously with estradiol. Replacement of estradiol-filled capsules for 3 h did not change the high rate of blood flow to the corpus luteum, but blood flow in the uterus, vagina, and ovarian stroma was increased. The injection of hCG (10 IU, iv) on day 10 of pseudopregnancy caused a 3-fold increase in blood flow to the nonluteal portion of the ovary and a 3-fold increase in the serum progesterone concentration, but luteal blood flow did not change. We conclude that the acute actions of estradiol or hCG in the rabbit corpus luteum are not mediated by changes in luteal blood flow. Further, the results suggest that the luteal vasculature is regulated differently from the vasculature of other estrogen-responsive tissues and that blood flow in the nonluteal tissues of the ovary can be regulated independently of blood flow in the corpus luteum. PMID- 2912689 TI - Evidence for a role of testosterone-androgen receptor interactions in mediating masculine sexual behavior in male rats. AB - The purpose of this study was 2-fold: 1) to use gonadal steroid hormone exposures in the physiological range to assess the relative roles of testosterone (T), estradiol (E2), and dihydrotestosterone (DHT) in the expression of male sexual behavior, and 2) to determine whether androgen receptor (AR) or estrogen receptor (E2R) occupation is increased after exposure to these various gonadal steroid hormones. Sexually experienced, castrated male rats implanted sc with Silastic capsules containing T, 10% E2, DHT, 10% E2 plus DHT, or blanks provided hormone levels in the physiological range. Copulatory behavior was measured on days 2-4, 5-7, 10-12, and 14-16 of steroid treatment. Although T, E2, and E2 plus DHT treatments all activated mounting, only T was effective in restoring ejaculation in 100% of the males. DHT alone had no effect on any aspect of male sexual behavior. Brains of males given these various hormone treatments were assayed for both cell nuclear AR and cell nuclear E2R binding in the hypothalamus, preoptic area, amygdala, and septum. Results indicate that when hormone levels in the physiological range were employed, T and DHT bind primarily to AR, whereas E2 binds to E2R. In a second experiment, 0.5% E2 plus DHT was found to yield AR and E2R levels comparable to those in rats receiving T capsules. Male rats bearing these capsules showed virtually no sexual behavior, demonstrating that elevation of AR and E2R levels comparable to those generated by T is not sufficient to induce male sexual behavior. We then measured intact AR and E2R levels and determined that in intact males E2R levels were higher than in T-treated males. These E2R levels could be replicated using 1.0% E2. Males exposed to 1.0% E2 plus DHT failed to display male sexual behavior. These data suggest that 1) relatively high and prolonged levels of E2R occupation are required for estrogen activation of male sexual behavior, 2) high levels of AR occupation induced by DHT are not sufficient to activate male sexual behavior, and 3) in intact male rats T, acting via androgen receptors, plays a primary role in mediating the expression of masculine sexual behavior. PMID- 2912690 TI - 5 alpha-reductase, aromatase, and androgen receptor levels in the monkey brain during fetal development. AB - To elucidate the metabolic fate and possible role of androgens and their derivatives during primate fetal development, aromatase (AROM), 5 alpha-reductase (5 alpha R), and androgen receptor (AR; cytosolic) levels were assessed in the brain, heart (HRT), lung (LNG), and skeletal muscle (MUS) of fetal rhesus monkeys. Analyses were performed on tissues taken on days 100 and 160 postconception. Five male and four or five female fetuses were examined at each stage. Brain tissues analyzed included medial basal hypothalamus (MBH), amygdala (AMG), cerebellum (CB), corpus callosum (CAL; splenial region), cerebral cortex (CTX), and cingulate cortex (CNG). In the following, enzyme activities are reported as picomoles per mg protein/h, while receptor levels are femtomoles per mg protein. 5 alpha R activity was measurable in all tissues. Analysis of variance revealed significant tissue differences [P less than 0.001, combined stages and sexes; CAL (2.05) greater than MBH (1.08) greater than AMG (0.63) greater than CB (0.4)-CNG-CTX-LNG-HRT-MUS (0.02); -indicates not significantly different]. A significant age x tissue interaction (P less than 0.001) was noted which could be explained by higher MBH and CAL levels in older vs. younger fetuses and higher AMG levels in younger vs. older fetuses. There was also a significant sex x tissue interaction which was attributed to higher female values in the MBH and CAL. AROM activity was detected in all tissues. Levels varied significantly among tissues [P less than 0.001, combined stages and sexes; MBH (0.80)-AMG (0.76) greater than CAL (0.4)-CNG-CB-CTX-LNG-HRT-MUS (0.07)]. Significant age (P less than 0.001) and age x tissue (P less than 0.001) effects were noted, which were due to higher MBH and AMG levels in younger vs. older fetuses. No sex difference in AROM levels was evident in any tissue. AR was measurable in all cases. Although stage and sex differences were not significant, tissue levels varied significantly [P less than 0.001; LNG (2.8)-MUS (2.6)-MBH (2.2) greater than HRT-AMG-CB-CTX-CAL-CNG (0.9)]. These findings indicate that neural and nonneural fetal primate tissues have the potential for transforming androgens to products that could have greater or lesser biological activity. AR were also noted through which dihydrotestosterone or testosterone could effect a genomic response. Since stage, tissue, and sex differences were evident in neural tissues, metabolic and receptor activities may be important for the normal differentiation of sexually dimorphic behavioral systems in monkeys as well as for potential teratogenic changes under abnormal metabolic or physiological conditions. PMID- 2912691 TI - Carbohydrate reactivation of thyroxine 5'-deiodinase (type II) in cultured mouse neuroblastoma cells is dependent upon new protein synthesis. AB - The T3 concentration in brain predominantly reflects local production from T4 rather than T3 uptake from the circulating pool. We recently demonstrated that rat brain T3 content is increased by glucose feeding compared to chow feeding. One possible mechanism for this effect is an increase in brain T4 5'-deiodinase (5'-D) activity. Our recent preliminary studies of neuroblastoma (NB) cells demonstrate that renewal of RPMI-1640 medium stimulates T4 5'-D type II (NB T4 5' D II) activity in these cells. The present studies were performed to determine the mechanism of this response. Studies were performed on NB cells supported in thyroid hormone-depleted (deficient) medium. This approach increased NB T4 5'-DII activity 4-fold compared to that in thyroid hormone-replete medium. Medium renewal further stimulated enzyme activity (7- to 9-fold; maximum at 6 h) in each group. The difference between the hypothyroid group and control was sustained over a 24-h period. Subsequent studies demonstrated that glucose (11 mM) was the specific medium ingredient mediating the medium renewal response. A progressive increase in NB T4 5'-DII activity was noted over 8 h during RPMI-1640 salt plus glucose (11 mM) incubation. This was equivalent to the effect of complete medium containing glucose (11 mM). Coincubation with insulin (10(-7)-10(-9) M) did not modify the enzyme response to glucose. In addition, fructose (10 mM) had a similar effect on enzyme activity. Glycerol and essential and nonessential amino acids also modestly increased NB T4 5'-DII activity compared to that in the control group (P less than 0.01). Actinomycin-D (1 microM), cycloheximide (100 microM), and puromycin (100 microM) significantly (P less than 0.001) decreased the glucose effect on T4 5'-DII by 5-, 9-, and 17-fold, respectively, after 6 h of incubation. In addition, puromycin (10-200 microM) inhibited both NB T4 5'-DII activity and [3H]amino acid incorporation during incubation in glucose. There was a significant correlation between these parameters (r = 0.8; P less than 0.001). The enzyme activity decay curves in the glucose-activated and control groups subsequent to puromycin (100 microM) addition at 8 h were parallel. The fractional turnover rate was 13%/h in the controls and 11%/h in the glucose groups. The calculated enzyme production rate was significantly higher (P less than 0.005) in the glucose group compared to that in the control group (17.4 vs. 6.8 fmol/mg protein.h).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2912692 TI - Synthetic parathyroid hormone-like protein-(1-74): biochemical and physiological characterization. AB - PTH-like protein-(1-74) [PTHLP-(1-74)] was synthesized and purified. On the basis of chromatographic criteria and amino acid composition of the full-length peptide, direct amino acid sequencing of the N-terminus, and amino acid composition and internal sequence of proteolytic fragments of PTHLP-(1-74), the synthetic peptide appears to be of high quality and purity. Physiological comparison of PTHLP-(1-74) to [Tyr36]-PTHLP-(1-36) amide and bovine (b) PTH-(1 34) indicates that all three peptides are of equivalent potency in the fetal rat long bone and rat osteosarcoma 17/2.8 adenylate cyclase assays. However, as in earlier studies with native and N-terminal PTHLPs, PTHLP-(1-74) is considerably less potent (2%) in stimulating the canine renal cortical adenylate cyclase assay than is bPTH-(1-34). Further, PTHLP-(1-74) displayed only 12% of the activity of bPTH-(1-34) in inducing hypercalcemia when infused into rats in vivo. These studies support the possibility that subclasses of PTH receptors or varying PTH- and PTHLP-signalling transduction mechanisms may exist. In addition, they emphasize the need to precisely define the naturally occurring secretory and circulating species of this novel class of peptide hormones. PMID- 2912693 TI - The effect of age on prostaglandin E2 stimulation of growth hormone release from cultured rat pituitary cells. AB - Prostaglandin E2 (PGE2) is a potent secretagogue of GH in mature mammals. Although PGs are produced by the fetus and newborn of many species, the ontogeny of PGE2's GH stimulatory effect and the interaction of PGE2 with GHRF in the developing animal are not known. We examined the effects of 0.01-10 microM PGE2 and 0.01-10 nM rat GHRF, alone and in combination, on GH release from cultured pituitary cells of 2-day(d)-old, 7-d-old, 15-d-old, and adult (3- to 4-month-old) male rats (n = 4-7 experiments/age group). The effect of PGE2 on GH release was markedly age dependent. The GH response to all doses of PGE2 over 0.01 microM was greatest in pituitary cells of adult and 15-d-old rats and least in those of 2-d old pups. PGE2 (0.1 microM) did not cause significant GH release from pituitary cells of 2-d-old pups (110 +/- 3% of control values), but increased that from 7-d old, 15-d-old, and adult pituitary cells to 126 +/- 8%, 155 +/- 8%, and 156 +/- 9% of respective control values (by analysis of variance: F = 7.28; P less than 0.001). PGE2 (1 microM) increased GH release to 123 +/- 8%, 145 +/- 12%, 259 +/- 24%, and 260 +/- 17% of control values from pituitary cells of these same respective age groups (F = 12.3; P less than 0.001). The highest dose of PGE2 studied (10 microM) yielded similar results. The influence of PGE1 on GH release was also age dependent and similar to that of PGE2. In contrast to PGE2, GHRF stimulated GH release most in pituitary cells of 2-d-old pups and least in those of adults, similar to our previous observations with human GHRF-40. Coincubation with PGE2 and low dose GHRF resulted in partial additivity of GH response in adult rats, but no additivity in newborn pups. These results indicate that in rats, the sensitivity of the somatotroph to PGE2 increases with advancing age after birth. The contrasting developmental patterns of somatotroph sensitivity to PGE2 and GHRF support the concept that these GH secretagogues act, at least in part, by different intracellular mechanisms, which are subject to differential rates of maturation. PMID- 2912694 TI - Properties of an adenosine triphosphate-stimulated factor that enhances the nuclear binding of activated glucocorticoid-receptor complex: binding to histone agarose. AB - Recently we have purified and characterized a factor in rat liver cytosol that enhances nuclear binding of the activated glucocorticoid-receptor complex in the presence of ATP [an ATP-stimulated translocation promoter (ASTP)]. It has a mol wt of 93,000, S value of 6.5, and pI of 4.5. Here we report studies on the binding of ASTP to histones from calf thymus. Higher salt concentrations were required to disrupt the binding of ASTP to histone-agarose than to disrupt its binding to the anion exchanger diethylaminoethyl-cellulose (half-maximal concentration for inhibition: 200 mM vs. 60 mM KCl). ATP decreased the binding of ASTP to histone-agarose in a dose-dependent fashion, but ADP and AMP had no appreciable effect on the binding. Pyridoxal 5'-phosphate (10 mM) inhibited the binding of ASTP to histone-agarose, whereas 10 mM pyridoxal, pyridoxamine 5' phosphate, pyridoxamine, and pyridoxine were not inhibitory. ASTP did not bind to histone-agarose that had been pretreated with pyridoxal 5'-phosphate and then reduced with sodium borohydride. In contrast, ASTP pretreated in the same way could bind to histone-agarose. Therefore, modification of lysine residues of histones by pyridoxal 5'-phosphate (Schiff base) presumably inhibited the binding of ASTP to the immobilized histone. Competition experiments with various histones (H1, H2A, H2B, H3, and H4) indicated that ASTP bound to the arginine-rich histones H3 and H4, with preference for H4. These observations together suggest that lysine residues in H4 and H3 are essential for the binding of ASTP to histone. The implications of this interaction are discussed. PMID- 2912695 TI - Neonatal organization of the brain opioid systems controlling prolactin and luteinizing hormone secretion. AB - It is known that the neural mechanisms which control PRL and gonadotropin secretion are different in male and female rats. The present experiments have been designed in order to analyze: 1) whether sexual differences exist in the responses of PRL and LH to the opioid antagonist naloxone; and 2) the mechanisms underlying these possible differences. To this purpose the responses of PRL and LH to the sc injection of either saline (0.5 ml) or naloxone (2.5 mg/kg) have been tested in the following four groups of animals: 1) normal male rats; 2) normal female rats; 3) female rats treated on the second day of life with 1.25 mg testosterone (androgenized female rats); and 4) male rats orchidectomized 2 days postnatally (demasculinized male rats). The naloxone challenge has been provided when the animals were 16, 26, and 60 days old; the animals were killed in the afternoon 20 min after treatment. The results obtained have shown that the acute injection of naloxone significantly decreases serum levels of PRL in normal males and in androgenized females at all ages considered. On the contrary, the opioid antagonist was always ineffective in normal females and in neonatally castrated males. The treatment of male rats with naloxone was without any effect on LH release before puberty (at 16 and 26 days of age), but induced a significant increase of serum LH titers after sexual maturation (60 days). In normal females, naloxone brought about a significant increase of serum LH only at 16 and 60 days (animals in estrus), but not at 26 days. Treatment with naloxone did not exert any significant effect on LH release in androgenized females and in deandrogenized males of any age. The present data suggest that, in the rat a sexual difference exists in the opiatergic control of PRL secretion; apparently, the central opioid systems which regulate PRL secretion develop towards a male pattern because of the presence of androgens in the neonatal period. On the contrary neonatal androgens do not seem to exert any important effect in directing the organization of the opiatergic mechanisms controlling LH release. PMID- 2912696 TI - Membrane receptor-mediated electrophysiological effects of glucocorticoid on mammalian neurons. AB - The nongenomic membrane receptor-mediated mechanism is an important but not fully explored facet in the action of steroid hormones. In the present study the action of glucocorticoid on nerve cell membrane was studied using isolated and superfused coeliac ganglion preparations by an intracellular electrophysiological technique. Glucocorticoid hyperpolarized the membrane potential of guinea pig ganglion neurons in vitro with a latency of less than 2 min. The effect persisted under low Ca2+/high Mg2+ superfusion conditions and could be abolished by RU38486, a competitive antagonist of glucocorticoid cytosolic receptor. Bovine albumin glucocorticoid conjugant exhibited the same effect. In neurons with spontaneous discharges the glucocorticoid-caused hyperpolarization of membrane potential decreased or eliminated the discharges. The results strongly suggest that glucocorticoid can act nongenomically through its neuronal membrane receptor. The steroid-induced hyperpolarization was accompanied by a change in the input resistance of the cell, indicating an involvement of some kind(s) of ion channel(s) in the action of glucocorticoid. PMID- 2912697 TI - Developmental pattern of 5 alpha-reductase activity in the rat gubernaculum. AB - 5 alpha-Reductase and aromatase activities were measured in fetal and newborn rat gubernaculum and other tissues by radiometric assays using [1 beta 3H]testosterone as substrate. Aromatase activity was measured by the stereospecific release of tritium into the incubation medium, and 5 alpha reductase was assessed by measuring the amount of 5 alpha-reduced steroids produced during the same incubations. Aromatase activity was low (less than 0.2 pmol/h.mg protein) in gubernaculum at all ages studied, whereas the activity in postnatal ovary ranged from 3.9-20 pmol/h.mg protein. 5 alpha-Reductase activity was relatively high in day 18 fetal gubernaculum (approximately 115 pmol/h.mg protein), but 2 days later in development (fetal day 20), 5 alpha-reductase activity had declined to approximately 21 pmol/h.mg protein. 5 alpha-Reductase activity was very low (less than 10 pmol/h.mg protein) in the postnatal gubernaculum. Histological examination of day 18 fetal gubernaculum indicated that it is composed of dense, poorly organized, mesenchymal tissue. By day 20 of gestational development, primitive muscle cells are recognizable in the periphery of the gubernaculum, and by day 3 of postnatal development the gubernaculum is composed almost entirely of muscle. These findings suggest that 5 alpha-reductase activity may be located in the mesenchymal cells and may be important in early differentiation of the gubernaculum in the male. The administration of a 5 alpha reductase inhibitor to pregnant rats from days 14-22 of gestation inhibited the normal growth rate of the gubernaculum, as assessed by measuring the protein content of the gubernaculum in control and treated rats, but did not have any profound effect on the histological development of the gubernaculum. PMID- 2912698 TI - Increased plasma 3,5,3'-triiodothyronine sulfate in rats with inhibited type I iodothyronine deiodinase activity, as measured by radioimmunoassay. AB - In contrast to the glucuronide conjugate, T3 sulfate (T3S) undergoes rapid deiodinative degradation in the liver and accumulates in rats and rat hepatocyte cultures if type I iodothyronine deiodinase activity is inhibited. We here report the RIA of plasma T3S in rats treated with the antithyroid drugs propylthiouracil (PTU) or methimazole (MMI), of which only PTU inhibits type I deiodinase. Male Wistar rats were treated acutely by ip injection with 1 mg PTU or MMI/100 g BW and subsequently for 4 days by twice daily injections with these drugs together with 0.5 microgram T4 or 0.25 microgram T3/100 g BW. Blood was obtained 4 h after the last injection, and plasma T4, rT3, T3, and T3S were determined by RIA and compared with pretreatment values. Serum concentrations (mean +/- SEM; nanomoles per liter) in untreated rats were: T4, 51 +/- 1; T3, 1.37 +/- 0.03; T3S, 0.09 +/- 0.01; and rT3, 0.03 +/- 0.002. Serum T3 was decreased, and T3S and rT3 were increased by acute PTU treatment [T3, 1.16 +/- 0.05 (P less than 0.01); T3S, 0.33 +/- 0.04 (P less than 0.001); rT3, 0.27 +/- 0.02 (P less than 0.001)], but unaffected by acute MMI treatment (T3, 1.37 +/- 0.05; T3S, 0.09 +/- 0.01; rT3, 0.02 +/- 0.003). In T4-treated rats, serum T3 was decreased and T4, T3S, and rT3 were increased by PTU vs. MMI [T4, 86 +/- 5 vs. 58 +/- 4 (P less than 0.001); T3, 0.51 +/- 0.07 vs. 0.88 +/- 0.06 (P less than 0.001); T3S, 0.38 +/- 0.03 vs. 0.12 +/- 0.01 (P less than 0.001); rT3, 0.86 +/- 0.19 vs. 0.08 +/- 0.01 (P less than 0.005)]. In T3-substituted rats T3S was increased by PTU vs. MMI (1.09 +/- 0.13 vs. 0.25 +/- 0.03; P less than 0.001). The T3S/T3 ratio in the PTU-treated T3 replaced rats (0.60 +/- 0.09) was in agreement with that determined by HPLC of serum radioactivity in animals that in addition to this treatment also received about 10 microCi [125I]T3 with the last two injections (0.92 +/- 0.13). In conclusion, this investigation demonstrates the feasibility of the measurement of serum T3S by RIA. Our findings confirm previous observations with radioactive isotopes, suggesting that sulfation is an important pathway for the metabolism of T3 in rats. Analogous to rT3, the accumulation of T3S in PTU-treated rats indicates that this conjugate is metabolized predominantly by type I deiodination. PMID- 2912699 TI - Kinetic studies on the development of the adult population of Leydig cells in testes of the pubertal rat. AB - The objective of this study was to determine whether postnatal increases in rat Leydig cell number result from differentiation of precursor cells, division of existing Leydig cells, or both. Our approach was 1) to examine changes in the absolute number of Leydig cells and potential precursor cells (macrophages, pericytes, and mesenchymal, endothelial, and myoid cells) per testis on day 19 of gestation (day -2) and days 7, 14, 21, 28, and 56 postpartum; 2) to examine the frequency with which mesenchymal and Leydig cells divide during prenatal and postnatal development; and 3) to identify and examine the fate of the progeny of Leydig and mesenchymal cell divisions during prenatal and postnatal development. Stereological methods were used to show that mesenchymal cells comprised 44% of the total interstitial cell population and Leydig cells 16% on day -2, whereas by day 56 postpartum the relationship had reversed; mesenchymal cells comprised 3% and Leydig cells 49%. These results suggested a precursor-product relationship between mesenchymal and Leydig cells because no such reciprocal relationship was observed between Leydig cells and macrophages, pericytes, endothelial, or myoid cells. Autoradiographic analysis of [3H]thymidine incorporation into mesenchymal and Leydig cells was consistent with this interpretation. In a series of pulse chase experiments, the percentage of labeled mesenchymal and Leydig cells was measured after a single injection of [3H]thymidine on days 2, 14, 28, and 56 postpartum, each followed by sampling at timed intervals (between 1 h and 14 days) thereafter. Starting on day 14, the percentage of labeled Leydig cells was approximately 1% immediately after injection of [3H]thymidine and increased significantly to approximately 6% by 6 days after injection. No such increase was observed when rats were similarly injected starting on days 2, 28, and 56 postpartum. The rise in Leydig cell labeling between days 14 and 28 postpartum did not result in a decline in the number of silver grains over labeled Leydig cell nuclei, indicating that the increase in the percentage of labeled cells was not caused by Leydig cell division. These observations led us to conclude that the increase in Leydig cell labeling from days 14 to 28 was the result of recruitment from a compartment of labeled mesenchymal cells. In contrast, our analysis indicated that from day 28 postpartum and thereafter until the mature number of Leydig cells is attained, Leydig cells are generated by division of morphologically recognizable Leydig cells. PMID- 2912700 TI - The androgen receptor of the testicular-feminized (Tfm) mutant mouse is smaller than the wild-type receptor. AB - The physicochemical and immunological properties of androgen receptors from kidney and brain of testicular-feminized (Tfm) mutant mice and wild-type mice were compared. Analysis by gel filtration and sucrose density gradients revealed that the mol wt of the mutant receptor was 66K (38A; 3.8S) which was significantly smaller than the 110K (53A; 4.6S) size of the wild-type androgen receptor (P less than 0.05). Mixing experiments failed to demonstrate any role for differential proteolysis in the size differences between these receptors. Interaction of the mutant androgen receptor with specific polyclonal antiandrogen receptor antibodies produced significantly smaller immune complexes than that formed with wild-type receptor (12S vs. 17S; P less than 0.01). This confirmed the smaller size of the Tfm mutant androgen receptor and suggested that it contained fewer epitopes. The Tfm kidney cytosols also demonstrated a decreased concentration of androgen receptor-binding activity relative to that of the wild type. Together, these results suggest that the androgen insensitivity associated with the Tfm phenotype is due to a deficiency of androgen receptor in target tissues and a qualitative defect in the androgen receptor protein itself. PMID- 2912701 TI - Evidence that neurotensin participates in the central regulation of the preovulatory surge of luteinizing hormone in the rat. AB - Neurotensin (NT) has been implicated in the central regulation of LH and PRL secretion in the rat. We investigated the importance of NT release to the neural events that trigger the preovulatory LH surge and coincident PRL surge, using as our animal model ovariectomized (OVX) rats treated with estrogen and progesterone to induce reliable and robust surges. To interfere with the action of endogenous NT in the basal forebrain, we administered a NT antiserum (NTAS) in a series of bilateral microinjections aimed at the anterior border of the medial preoptic area. One week after OVX, rats bearing cerebral guide cannulae received Silastic capsules (3 x 15 mm; sc) containing 17 beta-estradiol. Two days later, beginning at 0830 h, conscious rats were administered either NTAS or control serum bilaterally in a series of four 100-nl injections spaced at 30-min intervals. After an initial blood sample, rats received progesterone (4 mg, sc) at 1200 h; blood samples were then taken at 1-h intervals from 1400-2100 h. Blood samples were obtained from conscious, freely moving rats via a chronic atrial catheter implanted previously. Plasma levels of LH and PRL were measured by RIA, and the location of microinjection sites was verified histologically. Administration of NTAS caused a 66% reduction in the magnitude of the LH surge without altering its timing, whereas the PRL surge was unaffected. These results provide strong evidence that NT in the basal forebrain participates in the steroid-induced LH surge and suggest that NT plays a role in the preovulatory LH surge. PMID- 2912702 TI - Ovariectomy permits progesterone to increase the binding of [3H]spiperone to the anterior pituitary gland in estrogen-primed rats. AB - The binding of the dopamine (DA) D2 antagonist spiperone to DA receptors in the anterior pituitary gland was evaluated in intact and ovariectomized (OVX) estrogen-primed rats in which circulating levels of progesterone (P) were varied. Nembutal (PB; 35 mg/kg, ip) was administered at 1130 h to intact proestrous animals to prevent the LH-stimulated release of ovarian P. Two hours later some of these intact rats were QVX to remove the endogenous ovarian steroids. Both intact and OVX rats were given exogenous P. All rats were killed on the following morning, and adenohypophysial binding of [3H]spiperone was evaluated at a saturating concentration. The binding in intact PB-blocked rats that received P was only 52% of that in PB-blocked rats that were OVX and received P. The binding of [3H]spiperone in PB-treated rats that were OVX and given P did not differ statistically from that in normal estrous rats. A parallel experiment was conducted on other rats that had been OVX 7 days before the sc implantation (on day 0) of Silastic capsules containing estradiol (E2). Two days later (day 2), some of these rats were injected with Nembutal at 1130 h. Two hours later, the E2 capsules of some rats were removed to simulate ovariectomy; Silastic capsules containing P were implanted into both E2-bearing and non-E2-bearing rats. All rats were killed the following morning (day 3), and the density of adenohypophysial DA receptors was assessed. Binding densities were greatest in rats bearing both E2 and P capsules and in rats from which E2 capsules were removed and replaced with P capsules. We conclude that treatment of OVX rats with the sequential combination of E2 and P increases the density of DA receptors in the anterior pituitary gland. However, in intact rats an additional ovarian product prevents the P-induced increase in the density of adenohypophysial DA receptors. PMID- 2912703 TI - Oxytocin mediates the hypothalamic action of vasoactive intestinal peptide to stimulate prolactin secretion. AB - The ability of centrally administered vasoactive intestinal peptide (VIP) to stimulate PRL secretion when injected intracerebroventricularly could be due to leakage to the pituitary, where it is known to exert direct PRL-releasing activity, or to a hypothalamic action on its own release or that of another possible PRL-releasing factor. When 3 micrograms VIP were injected into the third ventricle of conscious ovariectomized rats, a significant (P less than 0.005) and transient elevation of plasma oxytocin (OT) levels was observed. When OVX rats were injected iv with 1 ml anti-OT serum 30 min before the central administration of 3 micrograms VIP, the PRL surge seen after VIP injection in normal rabbit serum-treated controls was completely absent. The PRL surge seen after central VIP administration was not significantly altered by iv saline infusion (1 ml over 30 min) or by infusion of a VIP antagonist [D-4-Cl-Phe6,Leu17]VIP at a dose of 0.5 microgram/kg.min in 1 ml saline for 30 min before the VIP injection. This was not due to the inability of the VIP antagonist to block the PRL-releasing factor activity of VIP, since it significantly antagonized that action both in vitro and in vivo in the suckling stimulation paradigm. However, the PRL surge was completely absent in ovariectomized rats pretreated by iv infusion of an OT antagonist, [deamino Cys1,D-Trp2,Val4,Orn8]OT, at a similar dose. This recruitment of OT by VIP indicates that it may act at more than one locus within the hypothalamo-pituitary axis to insure the coordinated control of PRL secretion. PMID- 2912704 TI - Induction of insulin-like growth factor I messenger ribonucleic acid during regeneration of rat skeletal muscle. AB - Expression of insulin-like growth factor I (IGF-I) was studied in regenerating skeletal muscle. Irreversible damage to muscle cells was induced in the extensor digitorum longus muscle of adult rats by ischemia, preceded by glycogen depletion. IGF-I mRNA levels during the regeneration process were studied for periods up to 10 days after injury using a solution hybridization assay. Increased IGF-I mRNA levels could be demonstrated within 24 h after injury; maximum levels were achieved in 3 days and decreased to approximately normal levels by 10 days. Changes in IGF-I mRNA levels could not be seen in undamaged contralateral extensor digitorum longus muscles during the experimental period. An increase in IGF-I mRNA was also evident in injured muscles of hypophysectomized animals. In situ hybridization at the time of maximum induction showed the presence of IGF-I mRNA in proliferating myoblasts and in satellite cells. IGF-I, thus, may act as a locally produced non-GH dependent trophic factor during regeneration of skeletal muscle after injury. PMID- 2912705 TI - The effects of high extracellular Ca2+ and Mg2+ concentrations on the levels of inositol 1,3,4,5-tetrakisphosphate in bovine parathyroid cells. AB - We examined the effects of calcium (Ca2+), magnesium (Mg2+), and fluoride ion (F ) on inositol phosphate accumulation in bovine parathyroid cells prelabeled with [3H] inositol to determine whether these agents might modulate cytosolic Ca2+ through accumulation of intracellular inositol 1,3,4,5-tetrakisphosphate (IP4), which has been postulated to be a mediator of the influx of extracellular Ca2+. Both Ca2+ and Mg2+ produced dose-dependent increases in IP4 in the presence of Li+, with maximal 19- and 4-fold increases with 5.0 mM Ca2+ and 20 mM Mg2+, respectively. A 50% rise in IP4 was evident within 1 min in response to 5.0 mM Ca2+. In the absence of Li+, a 2-fold increase in IP4 was seen with 5.0 mM Ca2+ only after 15 min. Fluoride ion generated a dose-dependent increase in IP4, with a 48% rise at 10 mM F-, presumably by activating phospholipase-C through a guanine nucleotide regulatory (G) protein-dependent process. We conclude that inositol 1,4,5-trisphosphate generated in response to high extracellular Ca2+ and Mg2+ concentrations can be converted to IP4 in parathyroid cells. The slow kinetics for the increase in IP4 with high Ca2+ in the absence of Li+, however, do not support a role for IP4 in the early phase of the sustained increase in cytosolic Ca2+ produced by high extracellular Ca2+ concentrations. PMID- 2912706 TI - The influence of genetic background on the expression of mutations at the diabetes locus in the mouse. V. Interaction between the db gene and hepatic sex steroid sulfotransferases correlates with gender-dependent susceptibility to hyperglycemia. AB - Steroid sulfurylation represents a potential mechanism for controlling the level of active steroids within a tissue. We have elucidated an inbred strain background-dependent interaction between the diabetes (db) mutation and steroid sulfotransferase (ST) enzymes, potentially modulating the level of active steroid hormones or their precursors in the liver. Gonadectomized mutants were analyzed to correlate how strain- and gender-dependent variation in ST activities interacted with db to achieve diabetogenesis. Both sexes on the C57BL/KsChp (BKs) background developed severe early-onset hyperglycemia, and gonadectomy failed to prevent diabetes. In contrast, C3HeB/FeChp (C3HeB)-db/db males, but not females, were diabetes susceptible, and the male susceptibility was completely dependent upon endogenous testes-derived testosterone. The female resistance, in turn, was dependent upon ovarian sex steroids. The differential requirements of BKs- and C3HeB-db/db males and females for gonadal sex steroids could be explained on the basis of the differential strength of the interaction between the db mutation and hepatic ST activities. Hepatic ST from normal adult females sulfurylated dehydroepiandrosterone (DHEA), whereas this activity disappeared in cytosols of normal adult males by 8 weeks of age. This sexually dimorphic inability to sulfurylate (pre)androgens was controlled by testosterone. Diabetogenic susceptibility in BKs mutant mice of both sexes was associated with marked depression of preandrogen/androgen sulfurylation [female mutants exhibiting at least a 5-fold reduced DHEA sulfurylation at a near-physiological concentration (0.2 microM)]. This reduced preandrogen/androgen sulfurylation occurred concomitant with a 10-fold acceleration of estrone (E1) sulfurylation at a limiting (0.2 microM) concentration, essentially producing a hyperandrogenized hepatic tissue state. These extreme shifts in ST substrate preferences were not observed in the diabetes-resistant C3HeB-db/db females. Kinetic analysis of semipurified hepatic ST from BKs-db/db females showed a 10-fold decrease in Km for E1 (apparent Km = 0.9 microM in mutants vs. 9.0 microM in normals). Whereas the Km for DHEA did not differ from the control value, hepatic ST from BKs-db/db females showed a 10-fold decreased maximal velocity for DHEA sulfurylation (1230 vs. 12750 pmol/mg.h in control preparations). The antihyperglycemic effects of dietary E1 therapy were associated with enhanced androgen sulfurylation in BKs db/db females and restoration of androgen sulfurylation in BKs-db/db males.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2912707 TI - Effect of thyroid hormone and growth hormone on recovery from hypothyroidism of epiphyseal growth plate cartilage and its adjacent bone. AB - Hypothyroidism was induced in young female Sprague-Dawley rats by the addition of methimazole (0.67 mg/ml) to drinking water for a period of 7 weeks (7-14 weeks of age). The responses of the articular cartilage, epiphyseal growth plate cartilage, epiphyseal trabecular bone, and metaphyseal trabecular bone in the proximal tibia were assessed by structural parameters. In addition, replacement therapies were introduced for the last 2 weeks of the experimental period. These included 0.7 U/kg BW human GH (hGH), 15 micrograms/kg BW L-T4 (T4), and a combination of hGH and T4 at the same doses. In the hypothyroid rats, the width of epiphyseal growth plate cartilage decreased by 27%, that of articular cartilage by 35%, epiphyseal trabecular bone volume by 30%, and metaphyseal trabecular bone volume by 66% relative to those in age-matched control tissues. T4 treatment led to a full restoration of the epiphyseal trabecular bone and surpassed by 40% the control value. The magnitude of the articular cartilage and the epiphyseal trabecular bone volume returned to control values, while that of metaphyseal trabecular bone was 68% of control values. Treatment with hGH did not improve the epiphyseal growth plate cartilage or articular cartilage. It did restore epiphyseal trabecular bone to almost normal values, but metaphyseal trabecular bone improved to only a small though significant level (45% of control value). The combination of T4 and hGH resulted in an additional enlargement in the width of the epiphyseal growth plate cartilage and an increase in metaphyseal trabecular bone volume compared to those in the T4 group. Qualitative examinations indicated that it was only in the T4 and T4 plus hGH groups that the lowest chondrocytes in the epiphyseal growth plate cartilage resumed their normal hypertrophied size. These results suggest that the change in the hypothyroid state do not rely solely on the lack of pituitary GH synthesis and secretion, as replacement by exogenous GH did not restore normal epiphyseal growth plate cartilage morphology or its remodeling into metaphyseal trabecular bone. Treatment with T4 (which restored endogenous pituitary GH to 30% of control levels) results in full recovery of the epiphyseal growth plate cartilage morphology along with its associated metaphyseal trabecular bone. In addition, it can also be concluded that the decrease in epiphyseal trabecular bone volume observed in the hypothyroid animals was due solely to the GH-deficient state that accompanied hypothyroidism. PMID- 2912708 TI - Homologous desensitization of ovarian luteinizing hormone/human chorionic gonadotropin-responsive adenylyl cyclase is dependent upon GTP. AB - Homologous desensitization of ovarian LH/hCG-responsive adenylyl cyclase in cell free systems has been reported to be dependent upon either ATP or GTP. We investigated LH/hCG-dependent desensitization of adenylyl cyclase in rabbit or pig ovarian follicular membranes and included adenyl-5'-yl imidodiphosphate to prevent nucleotide triphosphate degradation. It was found that GTP supported LH/hCG-induced desensitization with an apparent Km of approximately 0.1 microM in rabbit or pig ovarian membranes. Other nucleotide triphosphates were 100-1000 times less potent than GTP in supporting desensitization. Several nonhydrolyzable GTP analogs and the GDP analog guanosine-5'-O-(2-thiodiphosphate) would not support hCG-induced desensitization of ovarian adenylyl cyclase. Instead, these guanine nucleotide analogs were all inhibitors of GTP-supported hormone-dependent desensitization. Cholera toxin had no effect on LH-dependent desensitization. These results establish that GTP is the preferred nucleotide for homologous desensitization of the LH/hCG-sensitive adenylyl cyclase and that the GTP dependent mechanism differs from that typically associated with guanine nucleotide-binding proteins. The GTP-dependent mechanism of desensitization of the LH receptor distinguishes it from the ATP-dependent desensitization of the beta-adrenergic receptor. PMID- 2912709 TI - Uptake of 3,5,3'-triiodothyronine by cultured rat hepatoma cells is inhibitable by nonbile acid cholephils, diphenylhydantoin, and nonsteroidal antiinflammatory drugs. AB - Cellular uptake of T3 was examined using rat H4 hepatoma cells. Uptake of [125I]T3 (10(-11) M) from serum-free medium was measured as the cell-associated counts retained by washed cells (2 X 10(6) per well). Displaceable uptake was 84% of total uptake at 2 min (2.9% of total counts). T4, tetraiodothyroacetic acid, triiodothyroacetic acid, rT3, and D-T3 were 2-5% as effective as T3 in displacing uptake. Nonequilibrium kinetics indicated a half-maximal uptake at 680 nM T3 with approximately 7 million sites per cell. Displaceable uptake was time and temperature dependent and was 73% inhibited by 2 mM KCN and 52% by 10 mM bacitracin but not by 2 mM ouabain or 10 microM cytochalasin B. Phloretin, 100 microM, inhibited uptake by 66%. T3 uptake was directly related to the free T3 concentration over the range of albumin concentrations, 0-10 g/liter. The nonbile acid cholephil compounds, bromosulfophthalein, iopanoic acid, and indocyanine green (all 100 microM) inhibited T3 uptake to 62%, 17%, and 5% of control, respectively. Taurocholate, methylaminoisobutyric acid, and oleic acid were noninhibitory. The half-inhibitory concentrations of reactive nonsteroidal antiinflammatory drugs were: meclofenamic acid (25 microM), mefenamic acid (45 microM), fenclofenac (69 microM), flufenamic acid (100 microM), and diclofenac (230 microM). Aspirin, ibuprofen, oxyphenbutazone, and phenylbutazone (all 100 microM) were noninhibitory. Diphenylhydantoin inhibited uptake to 50% at 75 microM. These findings suggest that T3 uptake by cultured rat hepatocytes is by an energy-dependent, saturable, stereo-selective mechanism that is dependent on cell membrane proteins. This mechanism appears to be shared by a number of other ligands, including nonbile acid cholephils and several nonsteroidal antiinflammatory drugs of the anthranilic and phenylacetic acid classes, as well as diphenylhydantoin. The bile acid taurocholate, oleic acid, and a probe for type A amino acid uptake were inactive. The extent to which these effects may modify expression of thyroid hormone action remains to be established. PMID- 2912710 TI - Stage dependent expression of inhibin alpha and beta-B subunits during the cycle of the rat seminiferous epithelium. AB - In order to elucidate the putative role of inhibin in regulation of spermatogenesis, expression of inhibin subunits was examined at defined stages of the cycle of the rat seminiferous epithelium. Twenty 2-mm segments of seminiferous tubules at stages XIII-I, II-VI, VII-VIII, and IX-XII were dissected using the transillumination technique and subunit specific messenger RNAs (mRNAs) were quantitated by filter hybridization. The alpha and beta-B subunit mRNAs varied significantly in different stages, the highest levels of both alpha and beta-B subunit expression were seen in stages XIII-I and the lowest in stages VII VIII. The hybridization signals obtained with beta-actin probe were not significantly different between different stages indicating that the differences in the quantities of subunit mRNAs in different stages were not due to different amounts of RNA blotted. beta-A subunit mRNA levels were below the detection limit of the filter hybridization method. These data demonstrate that expression of inhibin alpha and beta-B subunits in the rat testis is stage dependent and suggest a paracrine role for inhibin-related peptides in regulation of spermatogenesis. PMID- 2912711 TI - Developing genetically epilepsy-prone rats have an abnormal seizure response to flurothyl. AB - Development of clonic-tonic flurothyl-induced seizures was examined in both normal and genetically epilepsy-prone rats (GEPRs). At each age, from 10 to 30 days, clonus occurred at significantly shorter latencies in GEPRs than in normal rats. The latency to onset of clonic seizures did not change with age, however, in either GEPRs or normal rats. A different pattern of response was observed in the progression to tonic seizures. As normal animals matured, the latency to tonic seizures became longer and, by day 30, the duration of flurothyl exposure necessary to induce tonus was almost 70% greater in normal rats than in the GEPRs. In contrast, in GEPRs, tonic extension occurred immediately following the onset of clonus throughout development. A subset of GEPRs failed to have audiogenic seizures in a 40-day posttest. These animals had a flurothyl response identical to their audiogenic-susceptible litter mates. These data suggest that (a) a protective mechanism which develops against tonic seizures in normal rats fails to mature in the GEPR, and (b) seizure inducing gene-linked neural abnormalities occur in the GEPR independent of pathologies underlying audiogenic seizures. PMID- 2912712 TI - Experience with the International League against Epilepsy proposals for classification of epileptic seizures and the epilepsies and epileptic syndromes in a pediatric outpatient epilepsy clinic. AB - The International League Against Epilepsy proposals for classification of epileptic seizures (1981) and of the epilepsies and epileptic syndromes (1985) have been used in daily practice in a pediatric epilepsy clinic in Bogota, Colombia. Most patients can be classified by these schemes, and the classifications are useful in everyday diagnosis and management. However, there are some drawbacks and difficulties with the classifications. Some syndromes are unnecessarily separated as different entities, artificially contributing to the complexity of the Classification. PMID- 2912713 TI - Oculoclonic status epilepticus. AB - Continuous oculoclonic status epilepticus occurred for 90 min in a 4-year-old girl. The seizure consisted of continuous contralateral horizontal nystagmus concurrent with left occipital spike discharges, occasional vomiting and no loss of consciousness. Oculoclonic status epilepticus may be a variant form of versive status epilepticus. PMID- 2912714 TI - Effects of antiepileptic drugs on GABA responses and on reduction of GABA responses by PTZ and DMCM on mouse neurons in cell culture. AB - The mechanisms of action of antiepileptic drugs effective against generalized absence seizures (antiabsence AEDs) remain uncertain. Antiabsence AEDs are generally effective against seizures induced in experimental animals by pentylenetetrazol (PTZ) and methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3 carboxylate (DMCM), drugs which reduce GABAergic inhibition. Thus, antiabsence AEDs have been suggested to enhance GABAergic inhibition. We studied the effects of several AEDs on GABA responses recorded from mouse spinal cord neurons grown in primary dissociated cell culture. Four antiabsence AEDs were included: ethosuximide (ESM), dimethadione (DMO), sodium valproate (VPA), and diazepam (DZP). Two experimental AEDs, CGS 9896 and ZK 91296, with anticonvulsant action against PTZ- or DMCM-induced seizures were also included. Possible effects of the antiabsence and experimental AEDS on PTZ- and DMCM-induced inhibition of GABA responses were also evaluated. PTZ and DMCM reversibly reduced GABA responses in a concentration-dependent manner. PTZ completely inhibited GABA responses at 10 mM (IC50 of 1.1 mM), whereas DMCM-induced inhibition of GABA responses reached a plateau level of 39% of control values at 1 microM (IC50 of 33 nM). ESM (1,200 microM), DMO (6 mM), VPA (200 microM), CGS 9896 (2 microM), and ZK 9896 (2 microM) did not alter GABA responses. DZP enhanced GABA responses in a concentration-dependent manner. The inhibition of GABA responses produced by PTZ 1 mM was unaltered by ESM (600 microM), DMO (6 mM), CGS 9896 (1 microM), or ZK 9896 (1 microM). Coapplication of VPA (200 microM) and PTZ (1 mM) slightly enhanced the PTZ effect. DZP (greater than 10 nM), however, reversed the PTZ induced reduction of GABA responses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2912715 TI - Upregulation of adenosine A1 receptors and forskolin binding sites following chronic treatment with caffeine or carbamazepine: a quantitative autoradiographic study. AB - The effects of feeding a diet enriched in caffeine or carbamazepine (CBZ) were investigated in rats in a quantitative autoradiographic study of adenosine A1 receptors (labeled by [3H]cyclohexyladenosine, [3H]CHA) and adenylate cyclase (labeled by [3H]forskolin). Although regional distribution of [3H]CHA and [3H]forskolin binding sites differed in some areas, chronic CBZ as well as chronic caffeine upregulated both of them. The changes in receptor densities occurred in the same brain microregions, suggesting that caffeine and CBZ act as antagonists at similar subpopulations of adenosine A1 receptors and [3H]forskolin binding sites. Therefore, a selective interaction of these two drugs with distinct adenosine A1 receptors (and adenylate cyclase) probably does not explain the differential effects of caffeine and CBZ on neuronal activity. PMID- 2912716 TI - Lack of effect of naloxone on prolactin and seizures in electroconvulsive therapy. AB - Both opiate agonist and antagonist injection have been reported to modulate prolactin secretion, alter brain excitability and produce seizures, and modify the postictal state. We studied the effects of administration of high-dose naloxone, an opiate antagonist, on postictal prolactin levels, seizure duration, and postictal behavior, using patients undergoing electroconvulsive therapy (ECT) as a seizure model. Seven patients had 8 mg naloxone injected prior to one ECT treatment and saline injected prior to another treatment, with the order of injection randomized. Before ECT and 15 min after ECT, prolactin levels were drawn, and no blunting of the expected postictal prolactin elevation by naloxone injection was observed. We found no evidence that endogenous opiates trigger prolactin secretion during seizures. Seizure duration was also similar in saline and naloxone groups, and naloxone did not reverse postictal depression, as has been reported in an animal model. PMID- 2912717 TI - Carbamazepine therapy and long-term prognosis in epilepsy of childhood. AB - Sixty-seven of 90 patients (74% who had been treated with carbamazepine (CBZ) alone were seizure-free for greater than 3 years. The EEG of the patients given CBZ monotherapy was more often normal in those without neurologic abnormalities other than mental retardation or a genetic predisposition. The prognosis of patients with partial seizures secondarily generalized was poorer than that of the other patients. Patients without mental retardation more often had monotherapy CBZ. The lowest blood level of CBZ for maintenance was considered to be 4 micrograms/ml, although the therapeutic blood level was between 6 and 12 micrograms/ml. Most of the side effects were mild. PMID- 2912718 TI - Neuroocular side effects of carbamazepine and phenobarbital in epileptic patients as measured by saccadic eye movements analysis. AB - The effect of carbamazepine (CBZ) and phenobarbital (PB), alone and in association, on the function of specific brain structures was studied in chronically treated epileptic patients by means of saccadic eye movements (SEMs) analysis. The relationship between daily fluctuations of CBZ plasma levels and the occurrence of intermittent side effects was also evaluated. All treatments produced a significant impairment (p less than 0.001) of SEM function as compared with a group of controls. SEM abnormalities appeared to change in relation to daily fluctuation of CBZ plasma levels. When the SEM parameters were considered separately, PB showed a significantly (p less than 0.001) more relevant sedative effect, whereas both drugs appear to produce the same effect on cerebellar and pontine functions. Although impairment of SEM function was most likely far from reaching clinical significance, it represents important information for the clinician. PMID- 2912719 TI - Comparison of steady-state blood levels of two carbamazepine formulations. AB - The steady-state plasma level produced by brand-name carbamazepine (CBZ) (Tegretol, Ciba-Geigy) was compared with a generic formulation (Parke-Davis) in 10 subjects with partial epilepsy in a randomized, double-blind, cross-over clinical trial. In addition, seizure frequency and clinical and laboratory signs of toxicity were evaluated. Our results failed to show any difference in CBZ blood levels, seizure frequency, or clinical or laboratory signs of toxicity in patients receiving either the brand-name or generic formulation. PMID- 2912720 TI - Anticonvulsant drugs selectively affect kindled and penicillin epilepsy, especially during seizure-prone sleep or awakening states in cats. AB - Carbamazepine (CBZ) selectively suppressed kindled convulsions, whereas ethosuximide (ESM) suppressed spike-wave activity accompanying systemic penicillin epilepsy in cats. Evoked potential data indicated that CBZ acted at the thalamic level, whereas ESM acted at cortex. Reduction of seizures and thalamic or cortical excitability occurred throughout the sleep-wake cycle, but effects were most pronounced in seizure-prone sleep or awakening states. These findings extend previous work showing differential antiepileptic drug (AED) effects on temporal lobe and absence seizures. The results are also consistent with recent work suggesting that thalamocortical pathways provide a final common pathway for the manifestation of sleep and awakening epilepsy and also reflect a chronic, latent pathophysiology. PMID- 2912721 TI - Successful treatment of massive carbamazepine overdose. AB - Overdose of carbamazepine (CBZ) can be fatal. We report the case of a patient with near-lethal toxicity due to delayed absorption of drug. A 36-year-old woman was admitted with coma, hypotension, and unusual movements. Carbamazepine (CBZ) level several hours later was 36 mg/L. Gastric lavage revealed no pill fragments, and activated charcoal was administered. CBZ level initially fell, reaching 28 mg/L 36 h after admission. Blood level then rose sharply, reaching 54 mg/L 64 h after admission. The pattern of rise suggested renewed absorption of drug. Vigorous cathartics were given, and further doses of charcoal were administered. Three hours after onset of diarrhea, roving eye movements occurred. Two hours later she grimaced to pain. Eight hours after the onset of diarrhea, she was awake. In CBZ overdose, activated charcoal therapy coupled with aggressive intestinal purging helps prevent continued absorption of drug, late exacerbation of symptoms, and potentially fatal outcome. PMID- 2912722 TI - Effect of gamma-vinyl GABA on interictal spikes and sharp waves in patients with intractable complex partial seizures. AB - The effect of gamma-vinyl GABA (GVG) on the interictal electroencephalogram (EEG) was studied in 13 patients with intractable complex partial seizures who participated in a single-blind, add-on, multicenter clinical trial of GVG. Precise operational definitions of epileptiform paroxysms were used to evaluate records before and after 3 months and 1 year of treatment with GVG. After 3 months of treatment, six patients exhibited reduction of both epileptiform paroxysms and seizure frequency, four had no change in seizure frequency nor in the EEG, and three had a reduction in seizure frequency but no concomitant reduction of epileptiform paroxysms in the EEG. Ten patients remained in the study after 1 year of treatment. In 4 patients both seizure frequency and EEG epileptiform paroxysms continued to decrease, in 1 patient both seizure frequency and number of EEG paroxysms increased, and in the remaining 3 there was no correlation between seizure frequency and EEG changes. PMID- 2912723 TI - The binding of double-stranded RNA and adenovirus VAI RNA to the interferon induced protein kinase. AB - The protein kinase from human cells dependent on double-stranded (ds) RNA is a 68 kDa protein (p68 kinase), the level of which is enhanced significantly in cells treated with interferon. When activated by low concentrations of dsRNA, the p68 kinase becomes phosphorylated and thereby catalyzes the phosphorylation of the protein-synthesis initiation factor, eIF2. Here, we have purified the p68 kinase to homogeneity using a specific monoclonal antibody to investigate its capacity to bind dsRNA, poly(I).poly(C). Our study suggest that p68 kinase has high- and low-affinity binding sites: the high-affinity binding site is responsible for the activation and the low-affinity binding site for the inhibition of kinase activity. This is in accord with the fact that autophosphorylation of p68 kinase occurs at low concentrations of dsRNA whereas high concentrations of dsRNA inhibit its autophosphorylation. We have also investigated the binding of adenoviral VAI RNA to the purified p68 kinase and have found that the affinity of this binding is lower than that of poly(I).poly(C). We show that VAI RNA can activate or inhibit autophosphorylation of p68 kinase in a dose-dependent manner, i.e. activation at less than or equal to 1 microgram/ml or inhibition at greater than 1 microgram/ml of VAI RNA. In spite of its lower affinity of binding, VAI RNA cannot be displaced by poly(I).poly(C) or reovirus dsRNA. These data confirm our previous results to illustrate that VAI RNA can bind p68 kinase and cause its inactivation irreversably. PMID- 2912724 TI - Altered expression of myosin light-chain isoforms in chronically stimulated fast twitch muscle of the rat. AB - Fast-twitch tibialis anterior muscle of the rat was chronically stimulated for periods of 18 days, 28 days and 56 days. Changes in the myosin light-chain (LC) pattern consisted in an increase in LC1f, concomitant with a decrease in LC3f. In contrast to previous findings in chronically stimulated fast-twitch tibialis anterior muscle of the rabbit, no substantial increases occurred in the slow myosin light-chain isoforms. In vivo labeling using [35S]methionine incorporation revealed differences in relative turnover between the fast myosin light chains. The relative turnover of the fast myosin light chains appeared to increase in normal muscle in the order LC2f less than LC1f less than LC3f. As judged from [35S]methionine incorporation, the changes in light-chain tissue content mainly resulted from altered synthesis rates. However, in the case of LC3f the decrease in protein content could not only be explained by a reduced synthesis, but, additionally, appeared to be due to enhanced degradation. Parvalbumin, which was included in the present study, was also found to decrease in the stimulated muscle. However, its decrease appeared to result primarily from reduced synthesis. PMID- 2912725 TI - cDNA cloning and complete primary structure of the small, active subunit of human carboxypeptidase N (kininase 1). AB - The human plasma metallo-protease carboxypeptidase N of Mr 280,000 consists of two small, enzymatically active subunits of Mr 50,000 and two large subunits. Only the large subunits are glycosylated. They may have a function in stabilizing the complex in plasma. The N-terminal sequence of the small subunit was determined from the isolated protein and used to specify a unique 59-mer oligonucleotide probe. A cDNA clone of 1.7 kbp containing the entire coding sequence of the small subunit of carboxypeptidase N was isolated from a human liver cDNA library. The cDNA clone encodes a signal sequence of 20 amino acids and the 438 amino acids of the mature subunit. There is a remarkable primary structure similarity of 49% to bovine carboxypeptidase E (enkephalin convertase). A more distant relationship to the bovine pancreatic, digestive carboxypeptidases A and B or even to the metallo-endopeptidases is based mainly on the occurrence of conserved, mechanistically important residues. PMID- 2912726 TI - Tropomyosin in the sea urchin egg cortex. AB - Tropomyosin was purified from the Triton-treated cortex fraction of fertilized sea urchin egg. Egg tropomyosin showed characteristics typical of nonmuscle tropomyosins such as low molecular mass, short periodicity of Mg2+-paracrystals, low lysine/arginine ratio, high Mg2+ requirement in binding to F-actin, in addition to the properties of all tropomyosins, namely, stability to high temperature, anomalous migration of SDS/urea gel, dissociation from F-actin under high ionic conditions and very acidic isoelectric point. Co-sedimentation assay of egg tropomyosin with actin in the presence of the previously purified high molecular-mass actin binding protein (260-kDa protein) showed that these two proteins bind to actin filaments in a non-competitive manner. This suggested that both the proteins play a cooperative role in the formation of actin-filament based cytoskeletal structure in the cortex. PMID- 2912727 TI - A 19F-NMR study of 2-fluoro-4-demethoxydaunomycin intercalation complexes with the decanucleotides d(G-C)5 and d(A-T)5. AB - Binding configurations and equilibria of intercalation complexes formed by the novel anthracycline drug, 2-fluoro-4-demethoxydaunomycin (2FD), with the decanucleotides d(G-C)5 and d(A-T)5 have been studied by 19F-NMR spectroscopy. The 19F chemical shift of 2FD bound to d(A-T)5 was approximately 1.5 ppm downfield of that observed for 2FD bound to d(G-C)5. By mixing equimolar amounts of aqueous d(G-C)5, d(A-T)5 and 2FD, the distribution of drug between the nucleotides was followed by observing relative peak intensities and showed no G-C or A-T binding preference at room temperature. It was shown that each decanucleotide duplex bound three 2FD molecules, giving a neighbour exclusion parameter, n, of n = 3 for this drug. The stoichiometric complexes, which we denote by [d(A-T)5][2FD]3 and [d(G-C)5][2FD]3, were also purified and isolated in this study. PMID- 2912728 TI - Heme may not be a positive regulator of cytochrome-P450 gene expression. AB - It has been proposed that transcription of cytochrome-P450 genes is positively regulated by heme, the prosthetic group of cytochrome-P450 proteins. We have investigated this proposal in rats treated with succinylacetone, a known specific inhibitor of the heme biosynthetic pathway. While 2-allyl-2-isopropylacetamide, phenobarbitone, dexamethasone, beta-naphthoflavone and clofibrate induced specific cytochrome-P450-mRNA species in rat liver, the levels of these induced mRNAs were not affected by succinylacetone administration. Synthesis of the first enzyme of the heme biosynthetic pathway, 5-aminolevulinate synthase, is known to be regulated by the end-product heme, with heme inhibiting 5-aminolevulinate synthase-gene transcription. Hepatic 5-aminolevulinate-synthase mRNA was induced by drugs and the level increased further by succinylacetone. Furthermore, treatment of rats with succinylacetone alone resulted in elevated levels of 5 aminolevulinate-synthase mRNA but did not affect cytochrome-P450-mRNA levels. The results show that while lowered heme levels lead to an increase in 5 aminolevulinate-synthase-mRNA synthesis there is no effect on cytochrome-P450 mRNA levels, implying that heme is not required for the cytochrome-P450-gene transcription. PMID- 2912729 TI - A crystallographic study of the glutathione binding site of glutathione reductase at 0.3-nm resolution. AB - The binding of glutathione, some related molecules and two redox compounds to crystals of glutathione reductase has been investigated by X-ray crystallography at 0.3-nm resolution. Models for several bound ligands have been built and subjected to crystallographic refinement. The results clearly show the residues involved in glutathione binding as well as the geometry of the disulfide exchange. Glutathione-I is bound in a V-shaped conformation, while glutathione-II is extended. The zwitterionic glutamyl end of glutathione-II appears to be the most tightly bound part of the substrate. All glutathione conjugates and derivatives studied show binding dominated by the interactions at this site. In the reduced enzyme, glutathione-I forms a mixed disulfide intermediate with Cys58. Other structural changes are observed on reduction of the enzyme, and it is demonstrated that the carboxamidomethylated enzyme is a good model for the reduced species. Lipoate, a weak substrate of the enzyme, assumes a defined binding site where its disulfide is available for being attacked by Cys58-S gamma. A second region with affinity for a number of compounds has been found in a large cavity at the dimer interface of the enzyme. No functional role of this site is known. PMID- 2912730 TI - Photochemically-induced dynamic nuclear polarization proton-NMR of aequorin discharged by calcium-independent light emission. AB - Photochemically-induced dynamic nuclear polarization was used to identify exposed amino-acid residues and to assign resonances in the 1H-NMR spectrum of Ca(II) independent discharged (inactivated) aequorin. A previous nuclear magnetic resonance, circular dichroism and fluorescence study [Ray, B.D., Ho, S., Kemple, M. D., Prendergast, F. G. and Nageswara Rao, B.D. (1985) Biochemistry 24, 4280 4287] indicated that as the Ca(II)-activated bioluminescent protein aequorin from jellyfish spontaneously emits light in the absence of Ca(II), it changes from a rigid, fully active form to a discharged form in which a number of amino-acid residues are more mobile than in the native protein. Laser-photochemically induced dynamic nuclear polarization experiments identified tryptophan and tyrosine residues, but not histidine residues, in Ca(II)-independent discharged aequorin to be accessible to the flavin dye used. These exposed residues are also among the mobile residues of the Ca(II)-independent discharged protein. Resonances of all the protons (including the alpha protons) of the accessible tryptophan and tyrosine residues were assigned with the aid of two-dimensional photochemically-induced dynamic nuclear polarization J-correlated spectroscopy. The oxidized chromophore, from which light is emitted in aequorin, was not accessible to the dye in the Ca(II)-independent discharged protein. No exposed residue was detected in the photochemically-induced dynamic nuclear polarization spectrum of Ca(II)-independent discharged aequorin from which the oxidized chromophore was removed, corroborating the previous finding that in this apo discharged form the protein partially refolds and thereby loses some of the mobility acquired in the formation of the Ca(II)-independent discharged protein. PMID- 2912731 TI - Interactions of concanavalin A with asparagine-linked glycopeptides. Structure/activity relationships of the binding and precipitation of oligomannose and bisected hybrid-type glycopeptides with concanavalin A. AB - We have recently demonstrated that certain oligomannose and bisected hybrid-type glycopeptides are bivalent for concanavalin A (ConA) binding and that they can precipitate the lectin [Bhattacharyya, L., Ceccarini, C., Lorenzoni, P & Brewer, C. F. (1987) J. Biol. Chem. 262, 1288-1293]. Two protein-binding sites on each glycopeptide were identified: one on the alpha(1-6) arm of the core beta-mannose residue which binds with high affinity (primary site); the other on the alpha(1 3) arm of the core beta-mannose residue which binds with lower affinity (secondary site). In the present study, we have investigated the relationship between the structures of the primary sites of oligomannose-type glycopeptides and their affinities for ConA. Two mechanisms of binding at the primary sites of oligomannose-type glycopeptides have been identified which account for the 3000 fold increase in affinity of a Man9 glycopeptide relative to that of methyl alpha D-mannopyranoside. Changes in the structures and affinities of both the primary and secondary sites are observed to influence the precipitation activities of the glycopeptides. These findings have important consequences for the specificity of ConA binding in solutions containing mixtures of the carbohydrates. PMID- 2912732 TI - Conformational analysis of the sialyl alpha(2----3/6)N-acetyllactosamine structural element occurring in glycoproteins, by two-dimensional NOE 1H-NMR spectroscopy in combination with energy calculations by hard-sphere exo-anomeric and molecular mechanics force-field with hydrogen-bonding potential. AB - The conformation is described of the sialyl alpha(2----3/6)N-acetyllactosamine structural element, frequently occurring in glycoproteins. NOE spectroscopy of NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----N)Asn and NeuAc alpha(2--- 6)Gal beta(1----4)GlcNAc beta(1----N)Asn is presented and for each glycosidic linkage, except for the alpha(2----6)-linkage, a number of interglycosidic NOEs are measured. The analysis of these effects is performed using a full relaxation matrix. Analysis of intraresidue NOEs provides a calibration of the calculation method. Hard-sphere exo-anomeric (HSEA) energy calculations indicate a single conformation for the beta(1----4)-linkage in both compounds, both being consistent with the NOE data. HSEA and molecular-mechanics force-field with hydrogen-bonding potential energy calculations both indicate the existence of three preferred conformations for the alpha(2----3)-linkage. The analysis of the NOE spectra are consistent with a distribution over two or three of these conformations; by combination with the energy diagram for this linkage the existence of onyl a single conformation can be excluded. The NOE spectrum of the compound with the alpha(2----6)-linkage indicates a gt orientation for the Gal C 6 hydroxymethyl group. On this basis, the HSEA energy calculations for the alpha(2----6)-linkage indicate an extended low-energy surface with a number of preferred conformations. The absence of NOEs across this linkage is interpreted in terms of a non-rigid, but overall folded conformation of the NeuAc alpha(2--- 6)Gal beta(1----4)GlcNAc beta structural element. This provides an explanation for the shift effects induced by alpha(2----6) attachment of NeuAc to the N acetyllactosamine unit. PMID- 2912733 TI - Interactions between discrete neuronal membrane binding sites for the putative K+ channel ligands beta-bungarotoxin, dendrotoxin and mast-cell-degranulating peptide. AB - 1. beta-Bungarotoxin, a presynaptically active neurotoxin from the venom of Bungarus multicinctus, was radiolabelled with 125I and its binding to synaptic membranes from rat brain was analyzed. The interaction of these binding sites with those for dendrotoxin (a convulsant polypeptide from mamba venom) and mast cell-degranulating peptide (from bee venom) was examined in the light of the known effects of all three toxins on voltage-dependent K+ currents. 2. When measured in Krebs/phosphate buffer, the binding appeared monotonic at low concentrations of radioiodinated beta-bungarotoxin (Kd 0.4 nM; Bmax 0.42 pmol/mg protein); higher concentrations of labelled toxin revealed an additional binding component of lower affinity, but computer analysis of the data failed to provide well-defined estimates of its Kd and Bmax values. 3. Equilibrium binding experiments conducted in imidazole-based buffers yielded distinctly biphasic Scatchard plots; computer analysis of the data revealed two populations of sites [Kd 0.26 (+/- 0.30) nM and 6.14 (+/- 5.68) nM; Bmax 0.16 (+/- 0.20) and 2.65 (+/- 1.21) pmol/mg protein]. 4. In Krebs medium, beta-bungarotoxin was a very weak antagonist of the binding of 125I-labelled dendrotoxin. In imidazole medium, however, the efficacy of the inhibition was markedly increased; analysis of this inhibition showed it to be non-competitive. 5. Dendrotoxin inhibited the binding of radioiodinated beta-bungarotoxin in Krebs medium with high potency, although the interaction was by a complex, non-competitive mechanism. 6. Mast-cell degranulating peptide inhibited non-competitively the binding of both radiolabelled dendrotoxin and beta-bungarotoxin but with relatively low potency. 7. A speculative schematic model of the dendrotoxin/beta-bungarotoxin/mast-cell degranulating peptide binding component(s) is proposed. Findings are discussed in terms of the likely involvement of these sites with voltage-dependent K+-channel proteins. PMID- 2912734 TI - Regulation of ornithine decarboxylase in murine erythroleukemic cells by N,N' diacetyl-1,6-hexanediamine and N-acetyl-1,6-hexanediamine. AB - The levels at which the ornithine decarboxylase gene is regulated in murine erythroleukemic cells treated with N,N'-hexamethylene bisacetamide (N,N' diacetyl 1,6-hexanediamine) and with N-acetyl-1,6-hexanediamine, the monoacetylated catabolite of this inducer of erythrodifferentiation, have been investigated. Although these two molecules are structurally related and both cause a decrease in ornithine decarboxylase activity, they did not similarly affect ornithine decarboxylase mRNA. In the presence of 4 mM N,N'-hexamethylenebisacetamide, at the concentration generally used to induce differentiation in these cells, a decreased steady-state level of ornithine decarboxylase mRNA, due to decreased gene transcription, was observed. In the presence of N-acetyl-1,6-hexanediamine the decrease in enzyme activity was shown to be associated with a decrease in the half-life of the enzyme in the absence of a change in gene transcription. These results show that in proliferating cultured cells changes in ornithine decarboxylase-gene transcription can be uncoupled from changes in cell growth and that N-acetyl-1,6-hexanediamine only regulates ornithine decarboxylase expression post-transcriptionally. PMID- 2912735 TI - Developmental regulation of expression of the regulatory subunit of the cAMP dependent protein kinase of Blastocladiella emersonii. AB - A monospecific polyclonal antiserum to the regulatory subunit (R) of the cAMP dependent protein kinase of Blastocladiella emersonii has been developed by immunization with purified regulatory subunit. In Western blots, the antiserum displays high affinity and specificity for the intact R monomer of Mr = 58,000, as well as for its proteolytic products of Mr = 43,000 and Mr = 36,000, even though the antiserum has been raised against the Mr = 43,000 fragment. Western blots of cell extracts prepared at different times during the life cycle of the fungus indicate that the increase in cAMP-binding activity occurring during sporulation, as well as its decrease during germination, are associated with the accumulation of the regulatory subunit during sporulation and its disappearance during germination, respectively. Pulse labeling with [35S]methionine and immunoprecipitation indicate that the accumulation of R is due to its increased synthesis during sporulation. Two-dimensional gel electrophoresis of affinity purified cell extracts obtained after [35S]methionine pulse labeling during sporulation confirms de novo synthesis of R during this stage and furthermore shows that the protein is rapidly phosphorylated after its synthesis. In vitro translation studies using RNA isolated from different stages of the life cycle followed by immunoprecipitation have shown that the time course of expression of the mRNA coding for the regulatory subunit parallels the rate of its synthesis in vivo. PMID- 2912736 TI - Quantitation of erythropoietin stimulatory activity using [3H]thymidine uptake by K562 cells. AB - A microassay for erythropoietin (Ep) activity in serum using [3H]thymidine uptake by K562 cells is presented. The method is similar to that of Krystal except that cells of the K562 human pluripotent leukemia cell line replace spleen cells from phenylhydrazine-treated anemic mice. Response to the hormone by K562 cells and spleen cells was colinear. Using the Krystal bioassay, 14 young hemoglobin S homozygotes had Ep activity levels of 17.9-113.8 mU/ml serum, whereas the new method with K562 cells gave a range of 19.2-115.3 mU/ml. The correlation coefficient between the two sets of data (r) was 0.999 (p less than 0.001). With the modified technique we have assayed 34 sickle cell patients, whose sera ranged from 19.2 to 1400 mU of Ep/ml with corresponding hemoglobin concentrations of 10.7 g % to 3.0 g %. Values for normal subjects were 22.1 +/- 2.1 mU/ml (n = 7). The stimulation of [3H]thymidine uptake is significantly inhibited by an anti-Ep antiserum. The assay permits quantification of stimulatory activities in a large number of samples with relative ease and is also suitable to explore the interactions of erythropoietic factors with their appropriate receptors on stem cells. PMID- 2912737 TI - Development of neomycin-resistant WEHI-3B D+ murine cells as an in vivo model of acute nonlymphocytic leukemia. AB - pSV2 neomycin DNA was electroporated into exponentially growing WEHI-3B D+ cells, and clones containing integrated pSV2 neomycin DNA were selected by treatment with the antibiotic Geneticin. Southern analysis after Eco RI or Bam HI and Hind III digestion demonstrated that two clones, Y1 and Y2, stably incorporated a single copy of intact pSV2 neomycin DNA into different sites. Exposure of parental WEHI-3B D+ cells to retinoic acid, aclacinomycin A, or adriamycin resulted in their differentiation to mature granulocytic cells. Clone Y1 had growth kinetics and numbers of differentiated cells comparable to those of the parental line when exposed to these differentiation-inducing agents. Furthermore, this clone was leukemogenic in BALB/c mice. The disease presented as a moderate anemia, a peripheral blood granulocytosis, a shift in the differential to immature granulocytic forms, and a thrombocytopenia. Although there was no change in bone marrow cellularity, in situ hybridization to identify the presence of the neomycin resistance gene mRNA indicated infiltration of leukemia cells (up to 30%) into this tissue compartment. The observed hematological parameters were indicative of a late stage of disease resembling human acute nonlymphocytic leukemia. Clone Y1, therefore, would appear to be an in vivo model of acute nonlymphocytic leukemia that may be useful for the development of therapeutic strategies to more successfully treat these diseases. Because we have demonstrated that this line is capable of differentiation in vitro and can be stably carried in vivo, it would also be useful for the identification of therapeutic agents capable of initiating the differentiation of leukemia cells in situ. PMID- 2912738 TI - Sexual dimorphism of erythropoietin-degrading activity in mouse submaxillary gland extracts. AB - In the course of investigation of submaxillary gland (SG) extracts from mice as a possible source of extra-renal erythropoietin (EPO) we have extended our previous studies of the degradation of EPO added to SG and kidney extracts. The discrepancy between estimates of EPO obtained with two radioimmunoassays (RIAs) differing only in time of incubation with 125I-labeled recombinant human EPO (r HuEPO) (20 h and 72 h) has been used as an indicator of tracer degradation occurring during the RIA incubation. Degradation of 125I-labeled r-HuEPO by male mouse SG extracts was not prevented by addition of inhibitors of monodeiodinases or proteolytic enzymes. Degradation of added 125I-labeled r-HuEPO was monitored using gel filtration fast protein liquid chromatography. SG extracts from male and androgen-treated female mice both degraded tracer r-HuEPO to a greater extent than extracts from female mice. Tracer degradation increased with time and tissue concentration and could give rise to invalid estimates of EPO in SG extracts by RIA. In contrast, none of the kidney extracts degraded r-HuEPO. Recovery of mouse serum EPO added to and incubated with male mouse SG or kidney extracts was 13% and 93%, respectively, estimated by RIA under conditions that excluded degradation of the RIA tracer antigen. PMID- 2912739 TI - The validity of salivary gland Epo estimates by radioimmunoassay (RIA) PMID- 2912740 TI - Mutagenicity of merocyanine 540-mediated photosensitization. AB - Merocyanine 540 (MC 540) is a photosensitizing dye with antineoplastic and antiviral properties. Because photoexcited MC 540 generates singlet molecular oxygen and possibly other reactive oxygen species there is concern that MC 540 mediated photosensitization may be mutagenic. In this paper, we report on the induction of ouabain- and 6-thioguanine-resistant mutants in Chinese hamster ovary (CHO) cells by MC 540 and light. Incubation with merocyanine 540 in the dark was not mutagenic. Simultaneous exposure to dye and high-intensity (70-75 W/m2) white or green light caused a small but significant increase in the frequency of both ouabain- and 6-thioguanine-resistant mutants. Similar increases in mutation frequencies were observed when the cells were exposed to white or green light in the absence of dye. When the fluence rate of the white light source was reduced by 50% (i.e., to 35 W/m2) but the duration of exposure doubled to keep the fluence constant, dye-mediated photosensitization and exposure to light alone generated few if any mutants. These results indicated that MC 540 mediated photosensitization is not mutagenic (as defined by the employed assays) as long as a nonmutagenic light source is used to excite the photosensitizer. They caution against the use of very powerful light sources in clinical applications of MC 540-mediated photosensitization. PMID- 2912742 TI - Natural killer cell-mediated inhibition of growth of myeloid and lymphoid clonogenic leukemias. AB - We have shown that peripheral blood (PB) lymphocytes of normal donors inhibit colony formation by myeloid (K-562) and lymphoid (Molt-4) leukemia cell lines in a clonogenic assay in vitro. The inhibitor cells were identified as natural killer (NK) cells based on their large granular lymphocyte (LGL) morphology and CD16+CD5- cell surface phenotype. The levels of inhibition were dependent both on the leukemia: effector (L:E) cell ratio, as well as on the time of preincubation of the leukemic and effector cells; maximum inhibition was observed at a 1:20 L:E cell ratio, and required 6-16 h preincubation of the leukemia and effector cells. Colony formation of both K-562 and Molt-4 was also inhibited by a soluble factor derived from coculture of K-562 and PB lymphocytes. The finding that the growth of clonogenic Molt-4 cells was almost completely abolished following treatment with interferon (IFN)-alpha rA in the dose of 10(3) U/ml, whereas growth of K-562 cells was only slightly affected by similar treatment, suggested that NK cells may mediate inhibition of clonogenic leukemias through various mechanisms. PMID- 2912741 TI - The concentration and resolution of primitive hemopoietic cells from normal mouse bone marrow by negative selection using monoclonal antibodies and Dynabead monodisperse magnetic microspheres. AB - High proliferative potential colony-forming cells (HPP-CFC) detected in clonal agar culture in the presence of the combined stimulus of colony-stimulating factor 1 (CSF-1) + interleukin 3 (IL-3) + interleukin 1 alpha (IL-1 alpha) are closely related to developmentally early progenitor cells capable of reconstituting the hemopoietic system of lethally irradiated mice following transplantation. Flow cytometric analysis and sorting of normal, unperturbed bone marrow has shown that HPP-CFC are B220- and 7/4-, whereas the committed progenitors of the macrophage lineage responsive to CSF-1 alone (CSFCSF-1) are B220- and 7/4+. Negative immunomagnetic selection using an anti-7/4, anti-B220 antibody cocktail and second-antibody-coupled Dynabead microspheres to replace flow cytometry results in the highly reproducible and specific enrichment of HPP CFC, and simultaneous resolution of HPP-CFC from CFCCSF-1. The tenfold enrichment of HPP-CFC compared with unfractionated bone marrow cell suspensions was comparable to that obtained by fluorescence-activated cell sorting. Enrichment was achieved with negligible loss of HPP-CFC at the immunomagnetic bead selection step, and 65% of HPP-CFC were recovered. The method is rapid, highly reproducible, and efficient, and has wide application to the separation of rare hemopoietic cells from normal bone marrow. PMID- 2912743 TI - Long-term effects of high doses of cytosine arabinoside on pluripotent stem cells (CFU-S). AB - The purpose of this work was to investigate the long-term effects of high doses of cytosine arabinoside (Ara-C) on the pluripotent stem cell (spleen colony forming units; CFU-S) compartment in mice. Studies were carried out on mice that survived the administration of repeated high doses of Ara-C (HDAra-C) with or without the injection of a partially purified CFU-S inhibitor or a bone marrow graft. The following features were examined 1, 1.5, and 5-7 months after treatment: CFU-S number, proliferative ability, and differentiation into different lineages. The results indicate that these parameters, which were severely disturbed soon after drug administration, returned to control levels within a month and remained unchanged as compared to age-matched controls for the following 6 months. Therefore, HDAra-C, given alone or with a CFU-S inhibitor or prior to bone marrow grafting, did not seem to induce long-lasting damage of the CFU-S compartment. However, our studies cannot eliminate the possibility of some residual stromal damage or some impairment of other properties of stem cells. It would be of importance to further clarify these points because HDAra-C are now used in the treatment of leukemias and prior to bone marrow transplantation. PMID- 2912744 TI - Correlation between erythropoietic activity and body growth rate in hypertransfused polycythemic growing rats as the result of an erythropoietin dependent operating mechanism. AB - The established relationship between erythropoietic activity and body growth rate in the polycythemic growing rat could be the result of either an erythropoietin (EPO)-dependent or an EPO-independent operating mechanism. The present study was thus undertaken to elucidate the nature of the aforementioned mechanism by assessing the ratio between plasma immunoreactive EPO (iEPO) concentration and erythropoietic activity in young hypertransfused rats for different body growth rates. Red blood cell (RBC)-59Fe uptake was about 75% in 21-day-old rats; it rapidly decreased with time when the animals were placed on a protein-free diet, approaching a level of about 1% by the 10th day of protein starvation. Over the same period plasma iEPO decreased from 55 mU/ml to 7 mU/ml. Body growth rate was 0. Following this "protein depletion period" the rats received diets containing different amounts of casein ("protein repletion period") added isocalorically to the protein-free diet to elicit a rise in body growth rate. Statistically significant relationships (p less than 0.001) were found between dietary casein concentration and body growth rate (r = 0.991), dietary casein concentration and RBC-59Fe uptake (r = 0.991), dietary casein concentration and plasma iEPO level (r = 0.992), body growth rate and RBC-59Fe (r = 0.986), and body growth rate and plasma iEPO level (r = 0.994) in hypertransfused polycythemic rats during the protein repletion period. These findings suggest that the correlation between erythropoietic activity and growth rate in the growing rat is the result of an erythropoietin-dependent operating mechanism, which appears to be independent of the ratio tissue oxygen supply/tissue oxygen demand. PMID- 2912745 TI - An in vitro model of wound healing in the CNS: analysis of cell reaction and interaction at different ages. AB - We have developed an in vitro model in which cells responding to trauma in the immature and mature CNS can be isolated, placed into serum-free culture, and characterized. By implanting nitrocellulose filters into the brains of neonatal and adult rats under different conditions, we are able to harvest populations of cells responding to trauma in the neonate (critical period implant), in the adult (scar implant), and in implants that have remained in vivo past the critical period (postcritical period implant). Upon placement in culture, we have found that astrocytes represent the majority of cells occupying both the critical period and postcritical period implants, whereas fibroblasts and macrophages represent the majority of cells in the glial-fibroblastic scar. The morphologies of the astrocytes on the surface of the different implants, after 3 days in culture, differs markedly--the critical period astrocytes exhibiting a more ordered distribution compared to the haphazard arrangement of astrocyte processes on the surface of the postcritical and scar implants. After migration from the implant, critical period astrocytes assume an epithelioid morphology and cluster together setting up definite boundaries between themselves and the endothelial cells. In contrast, postcritical period astrocytes exhibit a more elongated morphology under the same culture conditions and appear to be randomly dispersed among the endothelial cells. The scar astrocytes exhibit a wide range of morphologies and, although they tend to cluster, do not exhibit the ordered association seen with the critical period astrocytes. We propose that the plasticity of the neonatal astrocytes and the rapid and ordered cellular response seen in vitro reflect the ability of the immature CNS in vivo to respond to injury without the formation of a glial-fibroblastic scar. PMID- 2912746 TI - The convulsant effects of kainic acid microinjections into cerebral cortex are concentration but not laminar dependent. AB - The direct excitatory glutamate analog, kainic acid, when injected into different layers of the cat visual cortex, has two effects on this tissue that are fundamentally different from those exerted by the disinhibitory agents penicillin, bicuculline, and strychnine. First, both concentration-dependent suppression and convulsant activity was seen. Second, these concentration dependent influences were produced effectively in each cortical layer challenged despite a reported preferential localization of kainic acid receptors to layer 6. In contrast, the disinhibitory agents generally produce only convulsant effects, do so in a laminar-specific manner, and at significantly lower concentrations in intact brain (i.e., 50 microM vs 15 mM). These results suggest that kainic acid, in the concentrations employed here, has a generalized excitatory effect on all cortical circuitry and that it's convulsant influences are nonspecific and less potent than those of the inhibitory blockers. Further, a common neural trait shared by these different modes of epileptogenesis is discussed. PMID- 2912747 TI - Differentiation of substantia gelatinosa-like regions in intraspinal and intracerebral transplants of embryonic spinal cord tissue in the rat. AB - The differentiation of intracerebral and intraspinal transplants of fetal (E14 E15) rat spinal cord was studied to determine the extent to which myelin-free zones in these embryonic grafts exhibit cytological features and immunocytochemical characteristics of the substantia gelatinosa (SG) of the normal spinal cord. Immunocytochemical staining with antiserum to myelin basic protein (MBP) revealed myelin-free areas of varying proportions within fetal spinal cord grafts. These regions were identified in both newborn and adult recipients regardless of whether donor tissue was grafted to heterotopic (intracerebral) or homotopic (intraspinal) sites. As in the SG of the intact spinal cord, the myelin-free regions consisted mainly of small (7-15 microns) diameter neurons. At the ultrastructural level, these cells were surrounded by a neuropil composed of numerous small caliber, unmyelinated axons and intermediate sized dendrites. Synaptic terminals in these areas were primarily characterized by the presence of clear, round vesicles, although granular vesicles were occasionally found within these terminals. Immunocytochemical staining demonstrated met- and leu-enkephalin-, neurotensin-, substance P-, and somatostatin-like immunoreactive elements within these myelin-free areas. Thus, regions within embryonic spinal cord grafts undergo some topographical differentiation which parallels that of the normal superficial dorsal horn. The presence of SG-like regions illustrates the potential capacity of fetal spinal cord transplants for replacing some intraspinal neuronal populations at the site of a spinal cord injury in neonatal and adult animals. These graft regions may serve as a source of intersegmental projection neurons or establish an extensive intrinsic circuitry similar to that seen in the normal SG. In addition, the definition of these areas provides a useful model to study the innervation patterns of host axons that typically project to the substantia gelatinosa of the normal spinal cord. PMID- 2912748 TI - Correlative analyses of lesion development and functional status after graded spinal cord contusive injuries in the rat. AB - The development of both histopathological changes and functional deficits was quantitatively assessed after mild, moderate, and severe spinal cord contusive injuries. The cross-sectional area of the spinal cord at the epicenter (region of maximal damage) and the areas of hemorrhage, lesion, and remaining gray and white matter were determined from 15 min to 8 weeks after injury. From 24 h to 8 weeks after injury, functional deficits were quantified using a combined behavioral score (CBS) based on the results from a number of behavioral tests of function. Regression analysis was used to examine the correlations between the amount of residual white matter and both the severity of contusive impact and the functional deficit over time after injury. The area of hemorrhage at 15 min and 24 h was greater in the mild and moderate injury groups than after the severe contusive injury. Significant loss of gray and white matter occurred primarily between 24 h and 1 week after injury along with concomitant increases in the area of lesion. In the mild injury group the rate of lesion development appeared slower than that in the moderate and severe injury groups and significant white matter loss continued to occur between 1 and 4 weeks after injury. Behavioral tests of functional deficit were performed at 24 h and weekly thereafter. The development of stable functional deficits was observed beginning at 3 weeks after injury. There was a significant correlation between residual white matter and the degree of initial injury at 24 h after injury and all subsequent time points. However, a significant correlation between residual white matter and functional deficit, as measured by the CBS, was not observed at 24 h or 1 week but did develop by 4 weeks after injury. PMID- 2912749 TI - Bulbospinal and intraspinal connections in normal and regenerated salamander spinal cord. AB - The salamander is the only limbed adult vertebrate which can regenerate portions of cervical, thoracic, or lumbar spinal cord. While the salamander has been a popular model for regeneration of the spinal cord, it is still not known what portions of the nervous system participate in the regeneration process. In the experiments reported here we examine the bulbospinal and intraspinal projections to the lumbar spinal cord in normal and regenerated salamanders (Notophthalmus viridescens). HRP application to the lumbar enlargement of normal salamanders labeled cells in the ventral thalamus, the rostral tegmentum in the proposed homolog of the red nucleus, the reticular neurons of the rhombencephalon, and the midline regions of the rhombencephalon which are possibly equivalent to raphe nuclei of other vertebrates. In the brachial spinal cord HRP-labeled cells were located in dorsal, intermediate, and ventral regions of the spinal gray matter and tended to be located at the periphery of the gray matter. To examine the spinal circuitry of regenerated salamanders, animals received complete spinal transections at the junction of the thoracic and lumbar spinal cord, abolishing all spontaneous coordinated hindlimb and tail movements. Animals exhibited walking and swimming within 60 days at which time a pledget of HRP was inserted into a gap in the spinal cord made by a transection 10.0 mm (six animals) or 5.0 mm (one animal) caudal to the first lesion. On average, the number of HRP labeled brain stem neurons in regenerated animals was 40% of that found in normal animals. The number of labeled cells in the brachial spinal cord was within the range of normal animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2912750 TI - Facial nerve regeneration in the silicone chamber: the influence of nerve growth factor. AB - The role of nerve growth factor (NGF) was examined in the neural repair of adult rabbit facial nerves using an in vivo preparation. A 35-microliters nerve growth chamber was created by suturing the proximal and distal ends of a transected facial nerve (superior buccal branch) into a silicone tube. A gap of 8 mm in the chamber remained after removal of a 5-mm piece of nerve and insertion of the proximal and distal stumps into the tube. Animals were operated bilaterally; one side of the chamber was filled with NGF and the contralateral side was filled with Ringer's solution. Regeneration of the nerves was examined 1 to 5 weeks following the surgery. The caliber of the nerve bundle, the distribution pattern of regenerating motoneurons, axon number per fascicle, size distribution, and the total number of cells were compared to the preoperative morphology pattern found for that animal. Each buccal branch served as its own control. The NGF-filled chambers demonstrated an overall larger caliber of nerve regeneration at 5 weeks and a higher density distribution of axon growth at 3 and 5 weeks. In the early regeneration case (3 weeks), the axon growth profile exhibited more fascicles and less axons than the preoperative controls. In the more advanced state (5 weeks), the fascicle number was reduced and the axon number was increased. After 5 weeks of regeneration the number of fascicles was still more than that found in the preoperative state. Axon size at 5 weeks was 80% that of the preoperative controls and the thickness of the myelin sheath was less than the preoperative level. The histogram of the size distribution revealed the same distribution as in the preoperative control section. PMID- 2912751 TI - Allylnitrile: a compound which induces long-term dyskinesia in mice following a single administration. AB - A single oral dose of allylnitrile (ALN) in mice pretreated with CCl4 induced behavioral abnormalities such as circling, hyperactivity, and head twitching, which lasted for a 4-month observation period. Histopathologically hemorrhage, demyelinated fibers and necrotic neurons were observed in the midbrain and pons 40 to 50 days after the administration of ALN. The head twitching was either reduced by treatment with serotonin and dopamine antagonists or enhanced by a serotonin releaser, suggesting that both serotonin and dopamine systems are involved in the behavioral abnormalities by ALN. These disorders by ALN may be used as an animal model of the dyskinetic syndrome. PMID- 2912752 TI - Effect of hind-limb suspension on young and adult skeletal muscle. I. Normal mice. AB - The purpose of this study was to determine the effect of hind-limb suspension (HS) on morphometric, histologic, and contractile characteristics of fast extensor digitorum longus (EDL) and slow soleus (SOL) twitch muscles in adult and immature mice. Hind-limb suspension for 2 weeks was used to produce atrophy in two groups of mice, ages 4 and 12 weeks, with nonsuspended animals serving as controls. Young HS mice exhibited marked decreases in SOL weight, length, cross sectional area (CSA), twitch and tetanic tensions, and rates of tension development and relaxation, with increases in fatigue resistance. HS reduced the diameter of both type I and IIA fibers, increased the percentage of type I fibers, and decreased the percentage of type IIA fibers in both young and adult SOL. Muscle weight, length, CSA, IIA and IIB fiber areas, and maximum rate of tetanic tension development were decreased in EDL of young HS mice; fatigue resistance and EDL half-relaxation times were increased. For most parameters evaluated, slow twitch muscle was more affected than fast twitch. HS affected contractile characteristics less than morphometric or histologic parameters. Rates of tension development and relaxation were the contractile parameters most affected by HS, and the time parameters of contraction were least affected. For all measurements young mice were more affected than adult mice. PMID- 2912753 TI - Effect of hind-limb suspension on young and adult skeletal muscle. II. Dystrophic mice. AB - Disuse atrophy induced by limb immobilization reportedly protects dystrophic mouse muscle from histopathological changes. This study was conducted to determine whether disuse atrophy induced by hind-limb suspension (HS) limits the histopathology and contractile abnormalities typically observed in the dystrophic mouse. Two weeks of hind-limb suspension were applied to dystrophic mice (line 129B6F1) at two ages, 4 weeks (6 mice) and 12 weeks (8 mice). Thirty-one untreated dystrophics served as controls. In general, HS exaggerated the dystrophic signs, especially in the younger mice; it reduced animal weight, muscle weight, maximum tetanic and twitch tensions, and rates of tetanic and twitch tension development. HS further slowed the contractile properties of soleus (SOL) and extensor digitorum longus (EDL) muscles, and increased their fatigue resistance. HS reduced the size of type I and IIA fibers in the 6-week SOL and EDL, but not in the 14-week muscles. HS produced a preferential atrophy of SOL type I fibers, with a parallel increase in type IIA fibers. However, it did not alleviate the fiber size variability, degree of necrosis, central nucleation, inflammation, or muscle fibrosis in dystrophic muscles. These data demonstrate that disuse by hind-limb suspension does not prevent the histopathological deterioration or loss of muscle function in 6- and 14-week dystrophic mice. PMID- 2912754 TI - Effects of limited postnatal ethanol exposure on the development of myelin and nerve fibers in rat optic nerve. AB - This study was designed to morphologically evaluate the effects of limited postnatal alcohol exposure on the development of myelin and axons in the rat optic nerve. Rat pups were artificially reared on Days 5-18 with a supplemented milk diet fed via a chronic gastrostomy tube. Experimental animals received 4% ethanol in their diet on Days 5-9, otherwise the experimental and control animals received identical diets in identical volumes. Optic nerve tissues were prepared for electron microscopy on Days 10, 16, 22, 29, and 90. The cross-sectional areas of optic nerves were smaller, there were fewer myelinated nerve fibers per unit area, and the progress of myelination was slowed on Day 10 in the ethanol-exposed animals. All of these effects were compensated for at later times. The ratio of myelin thickness to axon diameter was similar in experimental and control animals, indicating that the interaction between axon size and myelin formation was not affected by alcohol. The general distribution of axon sizes was unaffected by ethanol except at 10 days when the largest fibers were smaller. There was no evidence of alcohol-induced degeneration of axons, myelin, or glial structures. Thus, alcohol exposure during myelin development causes a delay in myelin acquisition that is later compensated for. PMID- 2912755 TI - Schwann cell recruitment from intact nerve fibers. AB - Two proximal branches of the rat facial nerve were transected and anastomosed end to-end within a silicone tube, each of them being exposed to a massive invasion of ascending regenerating axons. The proximal nerves contained extremely large bundles of regenerated fibers, often associated with preexistent "parent fibers." The bundles showed many signs of rash and disordered cell proliferation and myelination. These included multiple Schwann cells surrounded by a common basement membrane, occurrence of different phases of myelination and even myelination of two axons by one Schwann cell. There was no evidence of mitogenic signals for fibrocytes. This model may be used for studying the mitogenic effect of axons on Schwann cells. It also suggests that so-called "groups of regenerating fibers" in neuropathy are caused by Schwann cell recruitment. PMID- 2912756 TI - Snug tubular enclosures reduce extrafascicular axonal escape at peripheral nerve repair sites. AB - A method of fascicular nerve repair utilizing silicone rubber tubes has been developed and tested in the dog whose nerves, like those of man, have a thick epineurial sheath. The closely fitting tubes provide a noncompressive enclosure which minimizes axonal escape and facilitates axon regeneration in at least two ways: First, they provide an impermeable conduit for endoneurial fluid whose constituents create an environment favoring the regeneration of axons and Schwann cells. Second, the biocompatible tube induces rapid development of a highly organized capsule which isolates the repair site, prevents adhesions, and strengthens the discontinuity. Enclosure of coapted fascicles also improves alignment of endoneurial components while providing space for the resolution of edema. The inert, noncompressive enclosures appear to minimize unregulated axonal growth at the site of injury by providing a qualitatively distinct environment from that in loose or open tubes. PMID- 2912757 TI - Assessment of peripheral nerve crush injury with cortical somatosensory evoked potentials in the cat. AB - Somatosensory evoked potentials (SEPs) were recorded from anesthetized cats to assess regeneration of the superficial radial nerve after crush injury. SEPs were recorded by epidural electrodes chronically implanted over the primary somatosensory cortex (SI) and elicited by electrical stimulation of the dorsal surface of the contralateral forepaw. The stimulation intensity and impedances measured across the skin-stimulating electrodes were maintained constant for each animal throughout the experimental period. SEPs which disappeared after the radial nerve crush were elicited within the first week by stimulation applied to skin nearest the nerve crush site. Radial nerve crush also affected the SEP elicited by stimulating the intact ulnar side of the forepaw. In all animals examined, the SEP amplitude evoked by stimulation of the skin supplied by the ulnar nerve increased immediately after radial nerve crush. As early as 4 days after nerve crush, SEPs were elicited by stimulating the distal region of the digits that had been denervated. This phenomenon might be accounted for by peripheral collateral sprouting of intact neighboring nerves and/or by central unmasking of ulnar median input from the denervated radial skin area. Within 117 days, SEPs were elicited by stimulation applied anywhere in the previously denervated forepaw area. The topographical amplitude distribution of SEPs after reinnervation was not identical to that obtained under baseline conditions. The use of SEPs for chronic recording is an effective means to monitor reinnervation of skin after peripheral nerve injury. PMID- 2912758 TI - Spinal cord lesions block seizures or delay their onset in myelin-deficient rats: evidence that generalized tonic seizures can be triggered by abnormal spinal cord activity. AB - The myelin-deficient mutant rat develops generalized tonic seizures and dies during the fourth postnatal week. Surgical constriction of the lower thoracic spinal cord, performed either after the seizures have appeared or before, eliminates the seizures, or delays their onset, and prolongs the life of the animals. These observations support the view that the seizures in these animals can be triggered by abnormal activity originating in the myelin-deficient spinal cord and can be blocked by preventing that activity from ascending to higher levels. Similar seizures and "paroxysmal" phenomena occur in other myelin deficient conditions including multiple sclerosis. PMID- 2912759 TI - Cortical muscarinic receptor function following quinolinic acid-induced lesion of the nucleus basalis magnocellularis. AB - Phosphatidylinositol metabolism, linked to muscarinic receptor activation, was studied in rat cortical slices after a unilateral quinolinic acid lesion to the nucleus basalis magnocellularis (nbM) or the cortex itself. The incorporation of [3H]inositol into inositol phosphate was measured in the presence of LiCl, followed by anion exchange chromatography to separate inositol phosphates. Carbachol produced a dose-related increase in the amount of inositol phosphate in both the control and the cortex from rats with lesions to the nbM. No significant difference in the accumulation of inositol phosphate was observed between the two groups. Destruction of cortical cells with quinolinic acid almost completely eliminated the activation of phosphatidylinositol metabolism by carbachol. These results suggest that muscarinic receptors linked to phosphatidylinositol metabolism in the cortex are localized on intrinsic cortical neurons and not on afferent terminals from basal forebrain cholinergic neurons. PMID- 2912761 TI - Aortic occlusion and reperfusion and conduction, blood flow, and the blood-nerve barrier of rat sciatic nerve. AB - We studied the effect of ischemia and reperfusion on blood flow, electrophysiology, and the blood-nerve barrier of the sciatic nerve of the rat. Ischemia for 10 to 60 min, with up to 3 h of reperfusion, was produced by closure and then release of a noose around the abdominal aorta. Nerve blood flow and function were measured serially using microelectrode-hydrogen polarography and electrophysiologic recordings, respectively. The integrity of the blood-nerve barrier was assessed using the permeability surface area product to [14C]sucrose. Ischemia of up to 30 min did not impair reperfusion. One hour of ischemia resulted in reperfusion abnormalities that affected about half of the nerves. The ischemic and reperfusion stresses did not disrupt the blood-nerve barrier to [14C]sucrose nor produce conduction block. Possible mechanisms for this resistance to ischemic and reperfusion injury are discussed. PMID- 2912760 TI - Short-term effects of intrathecal baclofen in spasticity. AB - Six patients with long-lasting spasticity resistant to different drug therapies including oral baclofen received a bolus injection of lumbar intrathecal baclofen. Electromyographic (EMG) reactions of leg muscles (soleus, tibialis anterior, quadriceps, and hamstrings) to standard stimuli and during attempts at voluntary activation were recorded before the drug injection and up to 3 h after the injection. Responses to joint movements, H-reflexes, ankle clonus, and defensive reactions were noticeably suppressed within 30-45 min after the injection and had practically disappeared after 2 h. Ankle clonus was seen only in patients with H-reflexes, and clonus disappeared when the reflex responses to the n. tibialis stimuli were absent. A decrease in clonus EMG burst amplitudes was accompanied by a decrease in the clonus frequency. These observations favor the autooscillation hypothesis of clonus. Baclofen injection led to improvement in selective voluntary activation of leg muscles in patients with residual motor control. These results suggest that execution of voluntary motor commands in the patients suffered from functionally abnormal spinal circuitry rather than from changes in the descending motor commands. Intrathecal baclofen appears to be an effective way of eliminating increased muscle tone and spasms which can allow for voluntary motor function when it is present. PMID- 2912762 TI - Role of endogenous adenosine in recurrent generalized seizures. AB - We induced generalized seizures by cortical injection of penicillin in anesthetized, paralyzed cats. After they had developed recurrent ictal-interictal ECoG cycling and fictive tonic-clonic motor convulsions (status epilepticus), we studied the effect of systemically administered neuropharmacological agents on the seizure cycling. Antagonists of adenosine receptors, theophylline and 8 cyclopentyltheophylline, increased the cycle period due to marked prolongation of duration of ictal discharge, often to more than 30 min. Dipyridamole, an inhibitor of adenosine reuptake, lengthened the interictal phase of the seizure with no effect on ictal duration. Antagonists of gamma-aminobutyric acid and opioid peptides had no effect on either ictal or interictal phases nor did the nonspecific neural excitant, doxapram. These findings suggest that a major mechanism of ictal-interictal cycling during status epilepticus is the alternating accumulation during the ictal phase and clearance during the interictal phase of the inhibitory neurochemical, adenosine. PMID- 2912764 TI - Radiation effects on man and animals. PMID- 2912763 TI - The uptake of [14C]deoxyglucose into brain of young rats with inherited hydrocephalus. AB - The effect of hydrocephalus on cerebral glucose utilization as reflected by deoxyglucose uptake has been examined in rats with inherited hydrocephalus at 10, 20, and 28 days after birth using a semiquantitative method. Injection of [14C]deoxyglucose intraperitoneally was followed by freezing the brain, sectioning, and quantitative autoradiography of 10 brain regions. Brain [14C] concentration, cortical thickness, and plasma glucose concentrations were measured. Maximal thinning of the cerebral cortex had already occurred by 10 days after birth, although obvious symptoms such as gait disturbance developed after 20 days. In control rats, the cerebral isotope concentration was lower and more homogeneous at 10 days than at 20 or 28 days, which may be a reflection of the use of metabolic substrates other than glucose in younger animals. In order to make comparisons between control and hydrocephalic groups, tissue isotope concentrations were normalized to cerebellar cortex which was not affected by the hydrocephalus at any age. In hydrocephalic rats at 10 and 20 days, the concentration of [14C] was lower in all areas except the inferior colliculi and pons but the reduction was only significant in the sensory-motor cortex at 10 days and in the caudate nuclei at 20 days. By 28 days after birth, all areas except the cerebellum (six cortical regions, inferior colliculi, pons, and caudate) had significantly lower isotope concentrations in the hydrocephalic group. It is concluded that cerebral glucose metabolism is significantly reduced by 28 days after birth in H-Tx rats with congenital hydrocephalus and that less marked reductions occur prior to 28 days. PMID- 2912765 TI - Effects of photoperiod, temperature and testosterone-treatment on plasma T3 and T4 levels in the Djungarian hamster, Phodopus sungorus. AB - The effects of photoperiod, temperature and testosterone treatment on plasma T3 and T4 levels were investigated in the Djungarian hamster. Plasma T3 level was affected by temperature (25 degrees C less than 7 degrees C) but not by photoperiod. Plasma T4 level was affected by photoperiod (short day less than long day) at 25 degrees C. Administration of testosterone increased plasma T4 level under short photoperiod at 25 degrees C. Thus, higher plasma T4 level under long photoperiod at 25 degrees C might be induced by testosterone. PMID- 2912766 TI - Effect of consumption of green and black tea on the level of various enzymes in rats. AB - Drinking of both green and black tea as the only liquid ingested resulted in significant decreases in the activity of transketolase in whole blood of rats both before and after the in vitro addition of thiamin diphosphate. Liver transketolase activity was decreased only by green tea. Mucosal transketolase activity was not affected by either type of tea. The activity of lactate dehydrogenase (LDH) was not affected by either type of tea, while whole blood LDH was decreased by both green and black tea. Neither tea had any affect on mucosal alkaline phosphatase, but thiamin diphosphatase activity was decreased by both teas. An increase in liver total thiamin resulted from the drinking of both types of tea. PMID- 2912767 TI - Lipid characterization and 14C-acetate metabolism in catfish taste epithelium. AB - The catfish, Ictalurus punctatus is an important model system for the study of the biochemical mechanisms of taste reception. A detailed lipid analysis of epithelial tissue from the taste organ (barbel) of the catfish has been performed. Polar lipids account for 62 +/- 1% of the total, neutrals for 38 +/- 1%. Phosphatidyl-cholines, serines and ethanolamines are the major constituents of the polar fraction. Plasmalogen concentration is high relative to that of non neural tissues. [14C]-Acetate is incorporated into cell lipid fractions after incubation of barbel tissue at 37 degrees C for 60 min. Percentage amounts of most lipids change with time during this in vitro incubation. The phospholipids are the most metabolically active fractions. This work yields information for continuing reconstitution experiments and indicates that the taste epithelium of this important model system is a metabolically active tissue capable of supporting lipid turnover/synthesis. PMID- 2912768 TI - Analysis of three laboratory tests used in the evaluation of male fertility: Bayes' rule applied to the postcoital test, the in vitro mucus migration test, and the zona-free hamster egg test. PMID- 2912769 TI - Polycystic ovaries treated by laparoscopic laser vaporization. AB - Eighty-five anovulatory women with polycystic ovaries were treated laparoscopically by argon, carbon dioxide (CO2) or potassium-titanyl-phosphate (KTP) laser vaporization. Ovulation occurred spontaneously postoperatively in 71%. Twenty of 38 (53%) women resistant to standard clomiphene citrate (CC) therapy ovulated spontaneously after laparoscopic laser vaporization of the ovaries. Seventeen of the remaining 18 patients responded to CC postoperatively. Of 47 patients ovulating preoperatively with CC, 40 (85%) ovulated spontaneously postoperatively. Postoperatively, 56% conceived within six months of laparoscopy. This included 58% of postoperative spontaneous ovulators and 52% of postoperative CC stimulated patients. The results suggest that selected patients with polycystic ovaries can be induced to ovulate and subsequently conceive by laparoscopically partially vaporizing their ovaries with laser energy. PMID- 2912770 TI - Videolaseroscopy for the treatment of endometriosis associated with infertility. AB - Recent advances in laparoscopic surgery have enabled the gynecologic surgeon to treat an increased number of diseases of the reproductive organs by using the laser through the laparoscope. This article reviews the results of 243 patients with infertility associated with endometriosis ranging in severity from mild to extensive who were treated by the same surgeon using CO2 laser laparoscopically with videocamera augmentation and control. Of the 243 infertility patients, 168 (69.1%) achieved pregnancy. The pregnancy rates were 71.8% in 39 patients with stage I disease, 69.8% in 86 patients with stage II disease, 67.2% of 67 patients with stage III disease, and 68.6% in 51 patients with stage IV disease. The life table and two-parameter exponential model were used to calculate monthly fecundity, "cure," and "probability of pregnancy" rates. The results indicate that videolaseroscopic treatment of endometriosis associated with infertility, in surgically experienced hands, is at least as efficacious as other forms of therapy for mild and moderate cases of disease, but appears to be more successful than laparotomy for the more severe and extensive stages of disease. PMID- 2912771 TI - Tubocornual anastomosis: surgical considerations and coexistent infertility factors in determining the prognosis. AB - To assess factors that may alter the pregnancy rate in women undergoing tubocornual anastomosis, the cases of 42 women were studied. Because a combination of surgical procedures was performed, the operative side deemed to be the best side was distinguished from the other side. The overall cumulative normal pregnancy rate was 56.0% after 2 years. Deep resection of the intramural tube and cases with technical difficulty had a reduced pregnancy rate. Neither the cornual pathology nor the presence of adnexal adhesions adversely affected the pregnancy rate. Associated infertility factors reduced the chances of conceiving. These factors should give a reliable prognosis to aid in the direction of postoperative management, particularly with regard to in vitro fertilization. PMID- 2912772 TI - Dieting causes menstrual irregularities in normal weight young women through impairment of episodic luteinizing hormone secretion. AB - Thirteen healthy, normal weight young women were studied throughout a control cycle and a diet cycle, during which they lost 1 kg per week on a vegetarian 800 kcal diet. Blood was sampled daily in the morning, and at weekly intervals, collected at 10-minute intervals for 6 hours. Follicle growth was monitored by ultrasonic measurement. All subjects showed normal cyclic gonadal function during the control cycle. Cyclic gonadal function remained unaltered in two subjects during the diet cycle. No dominant follicle developed in seven others, while another four showed apparently normal follicular development but impaired progesterone secretion by the corpus luteum. Comparison of both cycles revealed that episodic luteinizing hormone (LH) secretion during the follicular phase was altered by dieting. Average LH concentrations and the frequency of episodic secretions were significantly reduced during the follicular phase but not during the luteal phase. Follicle-stimulating hormone was unaltered. PMID- 2912773 TI - Effectiveness of vaginal bromocriptine in treating women with hyperprolactinemia. AB - Treatment of hyperprolactinemia with oral bromocriptine has been associated with a high incidence of side effects. The authors recently demonstrated that, in normal women, the vaginal route of administration was an effective and safe alternative to oral bromocriptine. To evaluate the effectiveness of vaginal bromocriptine in treating women with hyperprolactinemia, the authors treated 15 hyperprolactinemic women with daily vaginal administration of 2.5 mg tablets of bromocriptine. Serum prolactin (PRL) levels and vital signs were measured daily for 6 days, then weekly for 4 weeks. Gastrointestinal side effects were limited to a single episode of mild nausea, and two cases of transient constipation. In all patients there was a dramatic initial reduction in PRL in response to a single 2.5 mg dose of bromocriptine. In 13 patients PRL levels were maintained within the normal range with daily administration of 2.5 mg, whereas in two patients, PRL levels remained higher than normal despite an increase in bromocriptine dose to 5 mg. These results suggest that short term use of vaginal bromocriptine is a safe and effective method of therapy for hyperprolactinemia. PMID- 2912774 TI - Luteal phase defect: the possibility of an immunohistochemical diagnosis. AB - Monoclonal antibody D9B1 has been shown to bind to a carbohydrate epitope associated with high molecular weight secretory sialoglycoprotein(s) of human endometrium. The authors demonstrate that, in a group of 28 patients diagnosed on the basis of histopathologic assessment as exhibiting luteal phase defect, 68% reveal significantly diminished expression of the epitope. Furthermore, histologic assessment of the secretory activity in single glands does not correlate simply with the level of expression of the epitope. Of specimens from patients complaining of infertility, 92% showed defective production of the D9B1 epitope. Thus, D9B1 immunohistochemistry provides a new molecular criterion for defective endometrial function. PMID- 2912776 TI - Prognostic value of in vitro sperm penetration into hormonally standardized human cervical mucus. AB - To analyze the prognostic value of the sperm cervical mucus penetration test (SCMPT), fresh semen samples of 99 male patients under infertility investigation were exposed to capillary tubes filled with freshly obtained cervical mucus (CM) of the patients' wives (WCM), fertile donors (DCM), and bovine CM (BCM). The quality of the human CM was standardized by oral administration of estrogens. The overall pregnancy rate after 6 months was 17.2% (17/99), and was significantly different in couples with poor and good SCMPT with WCM (1/44, 2.3% versus 16/55, 29%; P less than 0.001) in a prospective study. Human CM was superior to BCM as a penetration medium in providing more information about sperm function. The results suggest that in vitro sperm penetration testing with hormonally standardized CM of female partners adds an important dimension to sperm analysis with regard to fertility prognosis. PMID- 2912775 TI - Subclinical autoimmunity in recurrent aborters. AB - Thirty-four women with habitual abortion (HA) were evaluated for the presence of lupus-associated autoantibodies, antisperm antibodies, and evidence of complement abnormalities. A control group of women who had only successful pregnancy outcomes also was studied. Fourteen HA women had anatomic, genetic, or hormonal causes for their pregnancy losses ("explained losses"), and 20 had no apparent causative factors ("unexplained losses"). Fifty percent of HA women with unexplained losses and 34% of women with explained losses had at least one abnormal result, but multiple autoimmune abnormalities were found only in women with unexplained losses. Anticardiolipin antibodies were found most commonly (30% of all HA women and 8% of controls). Two clinically normal HA women had multiple autoantibodies detected. This study suggests that recurrent pregnancy loss may be a marker for subclinical autoimmune disease. PMID- 2912777 TI - The clinical value of conventional semen analysis. AB - The objectives of this study were, firstly, to relate semen variables to treatment independent conception rates by life-table analysis after having accounted for known female factors; secondly, to assess the relationship between the length of involuntary infertility before investigation and the predictive value of semen parameters; and thirdly, to examine the relationship between the type of progressive spermatozoal motility and fertility outcome. Laboratory error in the assessment of semen variables was minimized by using one consistent observer. Seven hundred thirty-nine subjects were recruited to the study over a 34-month period, and a 96.5% follow-up rate was achieved. Where the female partner had regular spontaneous ovulation, no pelvic pathology, and more than 48 months' preceding infertility, the Grade 2 motile sperm density (the concentration of spermatozoa exhibiting slow or sluggish linear or nonlinear motility) was the variable that best predicted fertility outcome (X1(2) = 20.24, P less than 0.0001). Where the Grade 2 motile sperm density was below 5 X 10(6)/ml in the latter group (19%), no conceptions were reported at 32 months' follow-up. Semen variables were not of predictive value where there were fewer than 48 months' infertility before investigation, or where the female partner had ovulatory dysfunction or pelvic pathology. PMID- 2912778 TI - The measurement of hyaluronidase activity in human spermatozoa by substrate slide assay and its clinical application. AB - Acrosomal hyaluronidase activity of individual sperm can be detected by a halo formation around the sperm head on hyaluronic acid substrate slides. The following results were obtained by this method in clinical practice. A significant correlation was found between hyaluronidase activity and sperm concentration in male infertility. Hyaluronidase activity increased as the concentration of sperm increased, and the least hyaluronidase activity was determined at less than 10 X 10(6)/ml. The group with more than 40% motility had a higher hyaluronidase activity than other groups with poor motility. Although there was no significant correlation between hyaluronidase and cumulus dispersion and fertilization rates in immature oocytes, there was an excellent correlation in mature oocytes in human in vitro fertilization. These findings suggest that a newly developed assay will be useful for evaluating sperm fertilizing capacity. PMID- 2912779 TI - A new method of transcervical female sterilization: preliminary results in rabbits. AB - In search of an outpatient procedure for female sterilization, the authors performed the following animal study. Two groups of seven rabbits were subjected to laparotomy, hysterotomy, and hysteroscopy. The uterotubal junction (UTJ) was destroyed with bipolar electrical current, and a plug (Aqualloy, Drachten, The Netherlands) was inserted. The plug on the right side contained quinacrine (Q) in group A and platelet extract (PE) in group B. Histologic assessment by serial sections indicated occlusion of the UTJ in all but one case (96% success rate). This one failure is attributed to the technical difficulties associated with hysteroscopy in the rabbit. The authors project that this method may have the potential of becoming an acceptable outpatient procedure for female sterilization in the human. PMID- 2912780 TI - The clinical value of salpingoscopy in tubal infertility. AB - A specially designed rigid salpingoscope has been developed to allow inspection of the tubal mucosa during laparoscopy. The presence and extent of intratubal adhesion formation can be evaluated more accurately by this technique than by either HSG or laparoscopy. In 22 patients with bilateral hydrosalpinges, an intrauterine pregnancy rate of 59% was achieved in the group of patients with very mild mucosal lesions and absence of mucosal adhesions. PMID- 2912781 TI - Hyperglycemia and hyponatremia during operative hysteroscopy with 5% dextrose in water distention. AB - Operative hysteroscopy may result in profound hyperglycemia and hyponatremia when crystaloids containing glucose are used as a distention medium. Four patients undergoing operative hysteroscopy developed hyperglycemia in proportion to increasing operative time. None of five monitored patients undergoing diagnostic hysteroscopy developed clinically significant hyperglycemia. PMID- 2912782 TI - Assay characteristics of the immunoradiometric method for CA-125. AB - A nonlinear standard curve for the immunoradiometric method for determining CA 125 may result in an overestimation of values below 20 U/ml. Since the modification of the assay as described in the report eliminates the problem, we propose the use of this simple modification when using CA-125 determinations for evaluating women with endometriosis. PMID- 2912783 TI - Human chorionic gonadotropin levels in various compartments in disturbed early pregnancy. AB - The hCG level in the uterine cavity was higher than in peripheral blood in a case of choriocarcinoma and in patients with spontaneous expulsion of the conceptus. In two patients with missed abortion, the hCG concentrations in peripheral blood and in serum from the uterine cavity did not differ. In contrast, the hCG concentrations in PF in these patients were lower than in peripheral blood. The measurement of hCG in these compartments may provide evidence concerning the location of the trophoblast. PMID- 2912785 TI - Pregnancies in cancelled gamete intrafallopian transfer cycles. AB - Forty-four percent of started GIFT cycles were cancelled. Insemination and intercourse in the cancelled cycles yield a 23% and 10% pregnancy rate, respectively. PMID- 2912784 TI - Intramural ectopic pregnancy implanting in adenomyosis. AB - The clinical course of this 33-year-old gravida presenting at 16 weeks' gestation with hemoperitoneum was typical for suspected uterine rupture. Pathologic examination of the hysterectomy specimen supports the diagnosis of intramural pregnancy, representing the 15th case reported to date in the literature. Furthermore, there was histologic evidence of adenomyosis both within the sinus tract leading to the implantation site and throughout the myometrium. Documentation of implantation and development of ectopic pregnancy in adenomyotic myometrium should alert the clinician to the possibility of this rare pregnancy complication. PMID- 2912786 TI - Hypoosmotic sperm swelling test as a sperm function test. PMID- 2912787 TI - Sex selection. PMID- 2912788 TI - [Surgical methods for the management of impacted upper cuspids]. AB - Four methods are used which are: looping, wire-loop glueing, surgical transposition, preparing the "window". PMID- 2912789 TI - [Evaluation of the Schmuth index in orthodontic diagnosis]. AB - In the publication the orthodontic diagnostical systems of Pont and Schmuth are compared as the result of which in judging the premolar distance the Schmuth. PMID- 2912790 TI - [Possibility of follow-up evaluation of single-piece fixed dentures]. AB - The method of the so called "Silodent"-type (silicon gum impression material of medium flowing eonsisteney, Ferrokemia, Budapest) is reported on. PMID- 2912791 TI - [Principles and practical questions of oral endosseous implantation of DIAKOR aluminum oxide bioceramics. I. The implant]. AB - The dental enossal implants made of Hungarian base material, the artificial aluminium oxide bioceramics artificial roots are put into circulation under the trade name DIAKOR./. By this type of the oral enossal implants the frames of prosthetical activity employing the surgical and prosthetical methods in combination are extended. PMID- 2912792 TI - Effect of unbalanced diets on the long-term metabolism of a toxicant. 1. Lead in rats: preliminary note. AB - The aim of this study was the evaluation of the effect of dietary imbalances on absorption and distribution of lead in the female Sprague-Dawley rat. In this note preliminary results on the relationship between blood concentrations of lead and unbalanced diets are presented. Hyperproteic, hyperglycidic, hyperlipidic and balanced diets were prepared, and most of them included 15 mg/kg lead. Blood samples were collected at day 0, 21, 36, and 95 of the diets and analyzed by anodic stripping voltammetry (ASV). Lead uptake as a function of feed consumption was found to decrease in the order: balanced, hyperproteic and hyperglycidic, hyperlipidic diet. On the other hand lead blood levels were as follows (decreasing order): hyperlipidic, hyperproteic, hyperglycidic, balanced. Further research is being carried out on the influences of dietary imbalances on whole body distribution of lead. PMID- 2912793 TI - Digestible energy value of gums in the rat--data on gum arabic. AB - Male Wistar rats were fed a defined formula diet free from non-starch polysaccharides and either containing no additive or supplemented with gum arabic or cellulose or starch. Food and faeces were analysed by bomb calorimetry both to assess the effect of these substances on the apparent digestibility of dietary gross energy and to ascribe digestible energy values to the supplements. The former was not affected by starch and was decreased more by cellulose than by gum arabic. The energy values obtained were 17.4 +/- 0.4 kJ/g starch, 1.7 +/- 0.6 kJ/g cellulose and 14.7 +/- 0.5 kJ/g gum arabic. The latter is consistent with the high apparent digestibility of gum arabic in vivo and casts doubt on the validity of growth assay procedures that suggest a near-zero energy value for gum arabic. PMID- 2912794 TI - Volatile N-nitrosamines in Polish malt and beer. AB - A survey of Polish malt and beer for volatile N-nitrosamines has been conducted. N-Nitrosodimethylamine was found in malt at levels ranging from 0.2 to 3.6 micrograms/kg (average 1.5 micrograms/kg) and in beer at levels up to 0.3 microgram/kg (average 0.2 micrograms/kg). The use of indirect malt dryers is credited with the low levels of N-nitrosamines found. PMID- 2912795 TI - Excretion of tetracycline and chlortetracycline in eggs after oral medication of laying hens. AB - After dosing laying hens orally with tetracycline (TC) through either drinking water (0.25 and 0.5 g/l for 5 days) or feed (300 and 600 ppm for 7 days), and chlortetracycline (CTC) through feed (600 ppm) residues were determined by an agar plate diffusion technique in cylinders with Bacillus cereus as test organism, separately for albumen and for yolk. The sensitivity threshold was 0.07 micrograms/g in albumen and 0.15 micrograms/g in yolk for TC and 0.01 micrograms/g in albumen and 0.06 micrograms/g in yolk for CTC. Drug excretion via egg was 3-fold higher for TC than for CTC. The drug was excreted preferentially into the yolk (about 75% of the total amount) and the elimination period lasted between 6 and 11 days for TC and 9 days for CTC, after treatment. Tetracycline use in laying hens is discussed, taking into consideration the proposals presented by the joint FAO/WHO Expert Committee on Food Additives. PMID- 2912796 TI - Excretion of penicillins and cephalexin in bovine milk following intramammary administration. AB - The elimination into bovine milk of beta-lactam antibiotic residues (procaine penicillin G, cloxacillin, ampicillin, oxacillin, cephalexin) following intramammary administration of 10 preparations marketed in France was studied. The quantitative analysis of residues was carried out by a microbiological agar diffusion method using Bacillus stearothermophilus. Sensitivity ranged from 0.001 I.U./ml for procaine penicillin G and 0.001 micrograms/ml for ampicillin to 0.02 micrograms/ml for cephalexin. The mean periods of elimination on which withholding times are based were between four and seven milkings according to the drugs administered. PMID- 2912797 TI - Compatible limb patterning mechanisms in urodeles and anurans. AB - We have experimentally tested the similarity of limb pattern-forming mechanisms in urodeles and anurans. To determine whether the mechanisms of limb outgrowth are equivalent, we compared the results of two kinds of reciprocal limb bud grafts between Xenopus and axolotls: contralateral grafts to confront anterior and posterior positions of graft and host, and ipsilateral grafts to align equivalent circumferential positions. Axolotl limb buds grafted to Xenopus hosts are immunologically rejected at a relatively early stage. Prior to rejection, however, experimental (but not control) grafts form supernumerary digits. Xenopus limb buds grafted to axolotl hosts are not rejected within the time frame of the experiment and therefore can be used to test the ability of frog cells to elicit responses from axolotl tissue that are similar to those that are elicited by axolotl tissue itself. When Xenopus buds were grafted to axolotl limb stumps so as to align circumferential positions, the majority of limbs did not form any supernumerary digits. However, in experimental grafts, where anterior and posterior of host and graft were misaligned, supernumerary digits formed at positional discontinuities. These results suggest that Xenopus/axolotl cell interactions result in responses that are similar to axolotl/axolotl cell interactions. Furthermore, axolotl and Xenopus cells can cooperate to build recognizable skeletal elements, despite large differences in cell size and growth rate between the two species. We infer from these results that urodeles and anurans share the same limb pattern-forming mechanisms, including compatible positional signals that allow appropriate localized cellular interactions between the two species. Our results suggest an approach for understanding homology of the tetrapod limb based on experimental cellular interactions. PMID- 2912798 TI - Calmodulin-binding proteins are developmentally regulated in gametes and embryos of fucoid algae. AB - Calcium-binding proteins and calmodulin-binding proteins were identified in gametes and zygotes of the marine brown algae Fucus vesiculosus, Fucus distichus, and Pelvetia fastigiata using gel (SDS-PAGE) overlay techniques. A calcium current appears to be important during cell polarization in fucoid zygotes (K.R. Robinson and L.F. Jaffe, 1975, Science 187, 70-72; K.R. Robinson and R. Cone, 1980, Science 207, 77-78), but there are no biochemical data on calcium-binding proteins in these algae. By using a sensitive 45Ca2+ overlay method designed to detect high-affinity calcium-binding proteins, at least 9-11 polypeptides were detected in extracts of fucoid gametes and zygotes. All samples had calcium binding proteins with apparent molecular weights of about 17 and 30 kDa. A 17-kDa calcium-binding protein was purified by calcium-dependent hydrophobic chromatography and was identified as calmodulin by immunological and enzyme activator criteria. A 125I-calmodulin overlay assay was used to identify potential targets of calmodulin action. Sperm contained one major calmodulin binding protein of about 45 kDa. Eggs lacked major calmodulin-binding activity. A 72-kDa calmodulin-binding protein was prominent in zygotes from 1-65 hr postfertilization. Both calmodulin-binding proteins showed calcium-dependent binding activity. Overall, the data suggest that the appearance and distribution of certain calcium-binding and calmodulin-binding proteins are under developmental regulation, and may reflect the different roles of calcium during fertilization and early embryogenesis. PMID- 2912800 TI - Slowing of synapse elimination by alpha-bungarotoxin superfusion of the neonatal rabbit soleus muscle. AB - To examine the role of postsynaptic activity in regulating the rate of neuromuscular synapse elimination, contractile activity of neonatal rabbit soleus muscles was decreased by chronic superfusion of alpha-bungarotoxin (alpha-BGT) over their surfaces. Superfusion was begun at 6 days postnatal and continued for a variable duration (2 to 5 days) before muscles were analyzed. The percentage of polyinnervated fibers was assessed both physiologically and anatomically for alpha-BGT-treated muscles and their contralateral muscles, in addition to normal and control muscles of the same age. Within muscles exposed to alpha-BGT, polyinnervation was significantly greater than that for muscles from each of the control groups. The anatomical assay further revealed that the retention of polyinnervation in alpha-BGT-treated muscles was most pronounced near the muscle's surface, although end plates at the center were also affected. This finding, coupled with evidence that only a small percentage of the muscle fibers were completely inactivated, suggests that the activity block was also most pronounced near the surface and relatively low at the muscle's center. The percentage of end plates at which synapse elimination was delayed was greater than the estimated percentage whose activity was completely blocked, suggesting that synapse loss was slowed even in muscle fibers retaining some postsynaptic activity. These observations indicate that the rate of synapse elimination depends on the levels of functional acetylcholine receptors. This process could be mediated in a graded fashion by changes in postsynaptic activity (subthreshold or suprathreshold) or by a nonelectrical effect of blocking postsynaptic receptors. PMID- 2912799 TI - Expression of acetylcholinesterase during visual system development in Drosophila. AB - As in other insects acetylcholine (ACh) and acetylcholinesterase (AChE) function in synaptic transmission in the central nervous system of Drosophila. Studies on flies mutant for AChE indicate that in addition to its synaptic function of inactivating acetylcholine, this neural enzyme is required for normal development of the nervous system (J.C. Hall, S.N. Alahiotis, D.A. Strumpf, and K. White, 1980, Genetics 96, 939-965; R.J. Greenspan, J.A. Finn, and J.C. Hall, 1980, J. Comp. Neurol. 189, 741-774). In order to understand what role AChE may play in neural development, it is necessary to know, in detail, where and when the enzyme appears. The use of monoclonal antibodies to localize AChE in the developing visual system of wild type Drosophila has yielded the novel observation that AChE appears in photoreceptor (retinula) cells 4-6 hr after they differentiate and 3 to 4 days before they are functional. Three days later the staining in the cell body of these cells is reduced. Because retinula cells have no functional connections at the time when AChE is first detected, AChE can not be performing its standard synaptic function. Subsequent to the reduction of AChE in the retinula cells, midway through the pupal stage, the enzyme accumulates rapidly in the neuropils of the optic lobes of the brain. Thus, there is a biphasic accumulation of AChE in the developing visual system with the enzyme initially being expressed in the retinula cells and accumulating later in the optic lobes. PMID- 2912801 TI - Gastrulation and larval pattern in Xenopus after blastocoelic injection of a Xenopus-derived inducing factor: experiments testing models for the normal organization of mesoderm. AB - When a Xenopus XTC cell-derived mesoderm-inducing factor (MIF) is injected into the blastocoel of Xenopus embryos before gastrulation, they develop almost normally until just after the onset of mesoderm involution at the internal blastoporal lip. Cells from the entire lining of the blastocoel roof and inner marginal zone then undergo a synchronous, sudden change of contact and arrangement which resembles the transformation undergone by normal mesoderm at its time of involution at the vegetal edge of the marginal zone. We describe a dose-dependent spectrum of subsequent abnormalities in gastrulation and, in cases where gastrulation partially recovers, in the resulting larval pattern. Because of such recovery, embryos injected with widely different doses may appear equally abnormal at the early gastrula stage but very different by control larval stages. Extra spinocaudal axial patterns, in the area of ectopic mesoderm, are seen after MIF doses that just permit recovery of gastrulation. The sudden cellular transformation corresponding to involution, in the ectopically specified mesoderm, spreads throughout the animal cap within 15 min in individuals, at a time significantly later than the earliest normal transformation in the marginal zone. No systematic alteration could, however, be detected in its timing, in relation to a 250-fold range of injected MIF concentration or a 3.5-hr difference in time of injection. The severity of the effects on final embryonic pattern is largely independent of the blastular stage of injections. Splitting of the total injected dose into two, separated by 2 to 3 hr of blastular development, reveals that the degree of effect on gastrulation and patterning depends only upon the highest experienced concentration at any time before response. When fibroblast growth factor (bFGF), a different effective mesoderm inducer, is similarly injected, a similar abnormal cell behavior and ectopic mesoderm formation are seen, but beginning only at midgastrular stages some 1.5 hr beyond that characteristic of XTC-MIF. The findings are introduced and discussed in terms of models for the natural organization of the time course of gastrulation and mesodermal pattern. PMID- 2912802 TI - Tissue-specific transcriptional control of alpha- and beta-tropomyosins in chicken muscle development. AB - During muscle maturation, isoform switching of contractile proteins to attain the adult phenotype involves both stage-specific and muscle-specific regulatory mechanisms. Chicken pectoralis major (PM) provides an interesting model to study the latter since a specific pattern of tropomyosin (TM) with repression of the beta TM isoform is displayed by the adult PM. The developmental pattern of alpha and beta fast skeletal muscle tropomyosins' (alpha f and beta TM) RNAs was investigated with 3' untranslated region specific probes. In PM, the beta TM messenger ceased to accumulate after hatching through a transcriptional control, as shown by run-on assays, so that, at Day 8 ex ovo, no beta TM mRNA was detected. In this same muscle, in parallel with the disappearance of the beta TM mRNA, there was a boost in the accumulation of the alpha f TM mRNA. In the leg muscles, following hatching, there was only a moderate increase in the level of the alpha f TM mRNA, together with a slight decrease in the accumulation of the beta TM mRNA. Taken together, these results show that chicken muscle maturation involves tissue-specific transcriptional control of tropomyosin genes and could suggest a possible coordinate regulation of the two genes. PMID- 2912803 TI - Sperm from tw32/+ mice: capacitation is normal, but hyperactivation is premature and nonhyperactivated sperm are slow. AB - The t complex in the mouse is a large group of linked genes that affect sperm function in fertilization. In t/+ males, sperm carrying the t complex (t sperm) have normal fertilizing ability, while sperm carrying the normal homolog (+t sperm) are dysfunctional (P. Olds-Clarke and B. Peitz, 1985, Genet. Res. 47, 49). The specific step in fertilization which is dysfunctional, however, is not known. Two characteristics of fertilizing sperm, capacitation (the process by which sperm become capable of undergoing the acrosome reaction) and hyperactivation (the change in swimming behavior concomitant with capacitation), were assayed by objective methods in epididymal sperm from tw32/+ males of two strains, and compared to sperm from +/+ males of the same strains. Capacitated and acrosome reacted sperm were identified by a chlortetracycline assay (C.R. Ward and B.T. Storey, 1984, Dev. Biol. 104, 287). Hyperactivated sperm were identified by their path shape and swimming speed, using a computer-assisted motion-analysis system (J.M. Neill and P. Olds-Clarke, 1987, Gamete Res. 18, 121). Hyperactivation occurred significantly sooner among sperm from tw32/+ mice than among sperm from +/+ mice of the same strain, while the rates and maximal levels of capacitation and spontaneous acrosome reactions were normal. Of the nonhyperactivated motile sperm from tw32/+ mice, almost all were slower than sperm from +/+ mice of the same strain. While the effect of premature hyperactivation on fertilization is not clear, slow movements are likely to impair fertilizing ability. These results raise the possibility that the slow sperm are the dysfunctional +t sperm. PMID- 2912804 TI - Expression and function of the neurotransmitter serotonin during development of the Helisoma nervous system. AB - Exogenous serotonin has been shown to evoke a neuron-selective inhibition of neurite outgrowth and synaptogenesis in identified Helisoma neurons in vitro. We demonstrate here that serotonin is present in the embryonic nervous system of Helisoma and can act as a regulator of neuronal development in vivo. Serotonin like immunoreactivity was first observed in neurons at an early stage of nervous system development (E20). Throughout embryogenesis, the number of serotonin immunoreactive neurons increased in a stereotypic pattern that was unique for each type of ganglion. Strikingly, the number of serotonin-immunoreactive neurons continued to increase throughout adult life. Transient perturbation of endogenous serotonin levels during embryogenesis had profound effects on the development of specific identified neurons. Embryos treated with 5,7-dihydroxytryptamine and raised to maturity showed aberrations in neuronal morphology, neuronal dye coupling, and strength of electrical synaptic connections. These effects were restricted to neurons known to be sensitive to the growth-inhibitory effects of serotonin in vitro. These results support the hypothesis that neurotransmitters are an important class of regulatory factors during normal development of the nervous system. PMID- 2912805 TI - Disassembly of the nuclear envelope of spisula oocytes in a cell-free system. AB - Nuclei isolated from oocytes of the surf clam Spisula solidissima are disassembled when exposed to extracts from maturing oocytes. In the course of this process the nuclear lamina undergoes a marked reduction in size and the nuclear membrane appears to be fragmented into vesicles. These events are accompanied by extensive phosphorylation of the oocyte 67-kDa lamin and its solubilization. The changes observed are similar to those which occur in vivo in activated Spisula oocytes. Nuclear envelope breakdown in vitro requires ATP and Mg2+, but not Ca2+. It is not affected by protease inhibitors and is inhibited by alkaline phosphatase. PMID- 2912806 TI - Central projections of peripheral mechanosensory cells with increased excitability in Drosophila mosaics. AB - The formation and maintenance of the central projections of identified bristle mechanosensory neurons with altered excitability were examined in Drosophila mosaics. Two mutants, eag (ether a go-go) and Sh (Shaker), are known to increase excitability of both nerve and muscle cells and enhance synaptic transmission by affecting different types of K+ currents. The eag Sh double mutant produces a synergistic effect, resulting in a greatly increased level of spontaneous neuronal activity and extreme behavioral phenotypes. By constructing mosaic flies containing small patches of doubly mutant cuticle, it was possible to alter the excitability of only one or two identified sensory cells without affecting the surrounding tissue. In these mosaic flies, the doubly mutant sensory cells were more responsive to tactile stimulation. A CoCl2 backfilling technique was utilized in staining the sensory cell projections. Both qualitative and quantitative comparisons were made between projections of cells having normal and increased levels of excitability. The length, branching characteristics, and number of terminal varicosities were analyzed for each sensory cell projection. Results indicate that, at the light microscopy level, these characteristics were not obviously altered by an increased level of excitability. PMID- 2912807 TI - Reorganization and stabilization of acetylcholine receptor aggregates on rat myotubes. AB - Aggregation of acetylcholine receptors (AChRs) is an important early feature of the postsynaptic development of the vertebrae neuromuscular junction. At later stages of differentiation, aggregates are remodeled and stabilized. Aggregation of AChRs can be induced on rat myotubes in culture within 4 hr by treatment with embryonic pig brain extract (EBX). In this study, further sequential changes in the distribution of AChRs were followed by video-intensified fluorescence microscopy. These studies have revealed that groups of AChR aggregates that have formed after 4 hr in EBX are reorganized during the exposure to EBX for 20 additional hr to form a smaller number of larger, oval-shaped aggregates. We have named these two types of aggregates "4-hr aggregates" and "24-hr aggregates". This reorganization occurs by the expansion and merging of individual aggregates within a group, and by the incorporation of newly inserted AChRs. The 24-hr aggregates are an average of 15 times greater in area than 4-hr aggregates, and contain regions with an apparent AChR site density (fluorescence intensity) that is more than twice that of 4-hr aggregates. Electron microscopy of mapped 24-hr aggregates revealed that folded plasma membrane is associated with these regions, probably accounting for the elevated fluorescence. The 24-hr aggregates are more stable than 4-hr aggregates, as determined by their significantly slower disassembly after removal of EBX, elevation of temperature (38 degrees C), reduction of extracellular calcium levels (0.1 mM), or the addition of sodium azide (7 mM). This was determined by following disassembly both statistically (using fixed cultures) and by direct observations of living myotubes. These findings were confirmed by measuring the sequential changes in relative AChR site density over time in individual living myotubes. Thus, 24-hr aggregates form by the reorganization of 4-hr aggregates; exhibit a more regular, compact shape; and are more stable than 4-hr aggregates. These changes in AChR organization and aggregate stability resemble the changes occurring after the initial formation of junctional AChR aggregates during embryonic development, demonstrating additional similarities between this model system and the developing neuromuscular junction. PMID- 2912808 TI - Satellite cell proliferation and increase in the number of myonuclei induced by testosterone in the levator ani muscle of the adult female rat. AB - We injected adult female rats with 0.25 mg/100 g body weight of testosterone to test the sensitivity to androgens of the levator ani muscle (LAM). Testosterone induced marked hypertrophy characterized by fiber size enlargement, but did not increase the number of fibers. Morphological observations and quantitative data indicated that hypertrophy was accompanied by satellite cell proliferation between Days 1 and 3 after testosterone treatment, and by an increase in the number of myonuclei, which started between Days 2 and 3 after treatment. On Day 30, this increase reached 80% of the initial number of myonuclei. The new myonuclei seemed to result from satellite cell proliferation and from the fusion of some of them with preexistent muscle fibers. These results strongly suggest that testosterone-induced cell proliferation might have a role in developing the sexual dimorphism of the LAM. They also indicate the need to reconsider the currently accepted notion that sexual dimorphism is owing to female LAM involution. PMID- 2912810 TI - Chimeras between parthenogenetic or androgenetic blastomeres and normal embryos: allocation to the inner cell mass and trophectoderm. AB - A series of chimeras was generated by injecting single normal, parthenogenetic, or androgenetic blastomeres carrying transgenic markers under the zona pellucida of nontransgenic eight-cell embryos. These chimeras were cultured to the blastocyst stage and sectioned, and the transgenic component was detected by in situ hybridization. No statistically significant difference was found among the normal, parthenogenetic, and androgenetic chimeras in the number of chimeric blastocysts with a transgenic contribution to the inner cell mass (ICM), the trophectoderm, or both the ICM and trophectoderm. Since androgenetic and parthenogenetic cells were present in chimeras at a high frequency in both the ICM and trophectoderm at the blastocyst stage, but not in similar chimeras at late gastrulation, these cells must not respond normally to developmental signals subsequent to blastocyst formation and prior to late gastrulation. PMID- 2912809 TI - Centrosome inheritance in starfish zygotes: selective loss of the maternal centrosome after fertilization. AB - The mature egg inherits a centrosome from the second meiotic spindle, and the sperm introduces a second centrosome at fertilization. Since only one of these centrosomes survives to be used in development, specific mechanisms must exist to control centrosome inheritance. To investigate how centrosome inheritance is controlled we used starfish eggs as a model system, because they undergo meiosis after fertilization. As a result, the fate of the maternal and paternal centrosomes can be followed by light microscopy and experimentally manipulated in vivo. We show initially that only the paternal centrosome is used in starfish zygote development; the maternal centrosome retained from meiosis II is functionally lost before first mitosis. We then tested a number of possible ways in which the zygote could exert this differential control over the stability of centrosomes initially residing in the same cytoplasm. The results of these experiments can be summarized as follows: (1) Although the microtubule organizing center activity of the maternal centrosome is not degraded after meiosis, the ability of this centrosome to double at successive mitoses is lost. (2) The sperm centrosome is not "masked" from cytoplasmic conditions which could destabilize all centrosomes during or after the meiotic sequence. (3) The functional loss of the maternal centrosome is not due to its cortical location. (4) The loss of this doubling capacity is determined by the egg, not by putative inhibitory factors from the fertilizing sperm. (5) The destabilization of the maternal centrosome is not due to the complete loss of its centrioles. Together, these results demonstrate that all maternal centrosomes are equivalent and that they are intrinsically different from the paternal centrosome. This intrinsic difference, in concert with a change in cytoplasmic conditions after meiosis, determines the selective loss of the maternal centrosome inherited from the meiosis II spindle. PMID- 2912811 TI - Body scale and the development of prehension. AB - This study examined whether common dimensionless ratios define the critical point in the shifts in the grip coordination pattern of preschoolers and adults engaged in a displacement grasping activity with cubes that varied in object size. The findings indicated that there was an interaction between task constraints and organismic constraints in determining the grasping pattern utilized. However, when the object size is scaled to hand size there are common dimensionless ratios that correspond to the grasping patterns and the limb orientations employed across the age range utilized. Furthermore, 5 grip configurations accounted for the majority of grip variance in both age groups. The findings suggest a strong role for the impact of body scale on the development of coordination and provide preliminary evidence for the view that the development of prehension is a reflection of the constraints imposed on action. PMID- 2912812 TI - Maternal behavior of SHR rats and its relationship to offspring blood pressures. AB - In Part I of this study maternal behavior of 15 spontaneously hypertensive (SHR) and 11 Wistar-Kyoto (WKY) rat mothers was recorded throughout the preweaning period. SHR mothers were observed: 1) in arched-and blanket-nursing postures more often, and in passive-nursing posture less often, 2) licking their pups more often, and 3) resting less often. Further, SHR mothers retrieved their pups more quickly than did WKY. In the second part of this study we found that a composite maternal behavior score, derived from summing occurrences of mother/pup contact, arched-nursing, and pup-licking, was positively correlated with the offspring blood pressures. This relationship, which accounted for 43.5% of the variance in adult blood pressure, suggests that certain types of interactions between mothers and their pups may contribute to individual differences in cardiovascular system development. PMID- 2912813 TI - Relationships between maternal behavior of SHR and WKY dams and adult blood pressures of cross-fostered F1 pups. AB - In this experiment SHR and WKY dams reared genetically identical F1 pups derived from SHR x WKY matings. We found that a composite maternal behavior score was positively correlated with adult blood pressures of the fostered offspring. This replicated a similar finding from our previous study in which SHR and WKY mothers reared their own pups. Unlike this previous study, WKY dams rearing F1 pups exhibited maternal behavior patterns similar to SHR dams. Finally, we found there was no effect of the strain of foster mother upon adult blood pressures of the F1 offspring. These results indicate that some aspects of maternal behavior may change as a function of pup characteristics, and support our hypothesis that the cardiovascular system may be shaped by experiences of early life which are embedded in mother/young behavioral interactions. PMID- 2912814 TI - Amount of training and retention by infants. AB - In studies of animals and adult humans, more training typically leads to better retention. The generality of this finding was assessed in two studies with human infants in which amount of training was manipulated in two different ways. In the first study, 3-month-olds were trained for either 1, 2, or 3 sessions, each 9 min long; in the second, they were trained for a single session that was either 6, 9, 12, or 18 min long. Retention of independent groups was measured after delays ranging from 1 to 21 days. In both studies, different amounts of training did not yield group differences on any of the standard measures of acquisition or after a retention interval of 1 day. After intervals of a week or longer, however, more training led to better retention. Across studies, the long-term retention of groups that were trained for the same amount of time differed. We speculate that subjects learn different things in these two training regimens. PMID- 2912815 TI - Male rat pups are more hesitant to urinate in response to anogenital stimulation than are their female sibs. AB - Male rat pups required more anogenital stimulation before they began to urinate than did their sisters and males produced more urine than their female sibs during a fixed period of anogenital stimulation. These findings are interpreted as consistent with the view that neonatal mammals can manipulate the behavior of their dams. PMID- 2912816 TI - Gender and adjustment to chronic disease. A study of couples with colon cancer. AB - The adjustment of 39 couples in which one partner has cancer of the colon was assessed. The main findings were that the adjustment of male patients was superior to that of female patients. In the spouses' group the opposite was found, namely the adjustment of husbands was far worse than that of wives of cancer patients. PMID- 2912817 TI - Psychiatry and internal medicine resident education in an acute care medical psychiatry unit. AB - A Medical-Psychiatry Program has been developed at the University of Iowa. It includes a medical-psychiatry unit, a medical-psychiatry lecture series, a medical-psychiatry residency program, and a medical-psychiatry fellowship. The program enables residents pursuing straight psychiatry or internal medicine training to participate in a rotational experience requiring that they evaluate and treat patients for illnesses in both specialties under the supervision of both a staff psychiatrist and internist. During the rotation the resident learns how psychiatric and medical disease in the same patient complicates patient care and the skills needed to diagnose and treat such patients in the climate of their own specialty. The rotation is considered a valuable training experience by the majority of residents going through the rotation. PMID- 2912818 TI - Length of stay on a psychiatry-medicine unit. AB - To assess the efficiency of a medical-psychiatric unit over 3 years, several studies were carried out on one combined psychiatry-medicine unit. On the Behavior Evaluation and Treatment Unit of the Medical College of Wisconsin, Division of General Hospital Psychiatry, average length of stay was calculated in successive cohorts of 28-31 consecutive patients (total 358 patients). Medical surgical and psychiatric diagnoses were compared over a 2 1/2-year span; psychiatry diagnoses were compared to those on other units; and acuity of illness was measured comparatively by various methods. Length of stay decreased from more than 20 to less than 15 days. This effect did not appear to be directly related to diagnostic changes. Only minor increases in range of psychiatric diagnostic categories and changes in proportion of certain disorders were found. The acuity level was descriptively intermediate between that of a general medicine and that of a general psychiatry unit. Factors that could be related historically to these findings were discussed. PMID- 2912819 TI - Anxiety and depression in patients with the abdominal pelvic pain syndrome. AB - The authors matched gynecologic patients with the abdominal pelvic pain syndrome (N = 41) with other gynecologic patients. They administered to both groups self rating scales of anxiety, depression, anger-hostility, and somatization of the Hopkins Symptom Checklist and of the Symptom Questionnaire, a questionnaire about disruptions in early home life, and a questionnaire of recent stressful events. Patients with pain rated themselves on the average significantly more anxious, depressed, and hostile, and had more somatic symptoms than other patients; 56% of the patients with pain rated themselves within the normal ranges on all scales. There were no significant differences between the two groups in reports of disruptions of early home life and recent losses. The findings are consistent with the view that patients with the abdominal pelvic pain syndrome are psychologically a heterogeneous group; in many patients, depression and anxiety may be consequences of persistent pain. PMID- 2912820 TI - Differentiating multiple personality disorder and complex partial seizures. AB - A number of reports have suggested that some cases of multiple personality disorder might be due to temporal lobe epileptic discharges. We have administered a structured interview, the Dissociative Disorders Interview Schedule, to 20 subjects with multiple personality disorder, 20 with complex partial seizures, and 28 neurologic controls. Subjects also completed the Dissociative Experiences Scale. Results show that multiple personality can be differentiated from complex partial seizures on a large number of items. The seizure patients did not differ from controls. The data indicate that the phenomenologies of these two disorders are distinct, and, therefore, there is little reason to assume a common etiology. PMID- 2912821 TI - Teaching behavioral medicine in a primary care setting. An integrated approach. AB - The identification and management of psychosocial complaints is increasingly being recognized as an important function of primary care physicians. Residency programs are slowly incorporating training in behavioral medicine into their curricula. A wide variety of methods for teaching behavioral medicine have been used. This article describes a model in which behavioral medicine education is fully integrated into a primary care setting. PMID- 2912822 TI - Effects of a smoking ban on a general hospital psychiatric unit. AB - On January 1, 1987, the Board of Trustees of Southwest Washington Hospitals instituted a smoking ban in all of its facilities, including the 17-bed general psychiatry unit. Our study of ward atmosphere, PRN medications, and negative incidents related to that change are reported. We feel the change was introduced successfully with minimal impact on the successful function of our service. Others are encouraged to proceed with validation of our experience. PMID- 2912823 TI - Evaluation and treatment of sleep disorders in the medical setting. PMID- 2912824 TI - Catatonic syndrome associated with enteric fever. A case report. PMID- 2912825 TI - Effect of ambient oxygen concentration on lipofuscin accumulation in cultured rat heart myocytes--a novel in vitro model of lipofuscinogenesis. AB - The objective of this study was to elucidate the factors involved in the accumulation of lipofuscin in post-mitotic cells. The hypothesis that oxidative stress accelerates the rate of lipofuscin accumulation was tested by examining the effects of 5%, 20%, and 40% ambient oxygen concentration on lipofuscin content in cultured rat cardiac myocytes. Lipofuscin was quantified by microspectrofluorometry at 7 and 12 days of in vitro age. Lipofuscin-emitted yellow autofluorescence increased in direct relationship to ambient oxygen concentration with age. Transmission electron microscopic examination of the cells after 3, 8, and 12 days in culture indicated a progressive time and oxygen dependent increase in the frequency and size of lipofuscin organelles. The results are interpreted to suggest that oxidative stress is one of the causal factors in the accumulation of lipofuscin. PMID- 2912826 TI - Anoxic hepatocyte injury: role of reversible changes in elemental content and distribution. AB - Examination of anoxic isolated hepatocytes by light and electron microscopy indicated that initial morphologic changes were largely localized to the periphery of the cells. This early phase consisted of surface bleb formation but was not accompanied by alterations in parameters of plasma membrane integrity (leakage of cellular enzymes, exclusion of trypan blue). The time course of changes in structure was temporally related to alterations in the elemental distribution and content of various subcellular compartments. These studies, which employed electron probe X-ray microanalysis, demonstrated that rapid increases in the sodium and chlorine content and decreases in the potassium content of the cytoplasm, mitochondria and nucleus occurred, whereas no change in the calcium content of any subcellular compartment was detected. Concurrently, two cellular functions known to be dependent upon ion homeostasis, sodium dependent taurocholate uptake and mitochondrial respiratory control, became markedly impaired. Reoxygenation within 30 min resulted in the restoration of both elemental distribution and the latter two functions to baseline. These data are consistent with the hypothesis that some early functional changes may be mediated by altered ion homeostasis. In contrast, additional studies indicated that sodium and water fluxes could be dissociated from the appearance of plasma membrane blebs. Thus, this study provides direct evidence that the structural and functional changes of early anoxic hepatocyte injury cannot be explained by a single mechanistic cascade, but apparently involve multiple mechanisms which may not be directly linked. PMID- 2912827 TI - Hepatic asialoglycoprotein receptor-mediated binding of human polymeric immunoglobulin A. AB - In the rat, asialoorosomucoid and rat dimeric immunoglobulin A are both taken up by hepatocytes via receptor-mediated endocytosis. The fate of these two proteins, however, differs significantly. Rat dimeric IgA is taken up into smooth vesicles, transported to the bile canaliculus and secreted intact into the bile, whereas asialoglycoproteins are internalized via coated vesicles and transported to lysosomes for degradation. Recently, several studies both in the rat and in cultured human hepatoma cells have suggested that the receptor for asialoglycoproteins may play a role in the hepatic uptake and processing of human polymeric IgA. Using receptor-binding techniques, we have provided quantitative data for the competition of human monomeric, polymeric and secretory IgA with asialoorosomucoid for its receptor on liver plasma membrane preparations from rat, monkey and man. Some IgA molecules required desialylation with neuraminidase to enhance markedly their efficacy for asialoorosomucoid inhibition. Quantitatively, human IgA molecules showed an affinity for the ASOR receptor similar to that for asialoceruloplasmin. Rat dimeric IgA does not compete for this binding site. We conclude that human IgA can compete with ligands for the asialoglycoprotein receptor of rat, monkey and human liver. This receptor may provide an alternative pathway for the hepatic processing of IgA and IgA immune complexes when secretory component-mediated uptake is not available as in the monkey and man, particularly under pathological conditions where serum IgA concentrations accumulate to abnormally high levels. PMID- 2912828 TI - Differential regulation of glutathione S-transferases in cultured hepatocytes. AB - Specific cDNA probes were used to determine steady-state mRNA levels for the multiple glutathione S-transferases in primary hepatocyte cultures. In the first 24 hr of culture, gene transcripts for the Ya family decreased sharply, Yb3 disappeared completely, but changes in levels of mRNA for Yb1 and Yb2 were smaller. These results suggest that the isoenzymes are regulated independently. Yp mRNA, which is present at greatly elevated levels in hyperplastic nodules and hepatocellular carcinomas but not in normal adult livers, was hardly detectable in freshly isolated hepatocytes, but Yp transcripts rapidly accumulated in the first 24 hr in culture and continued to increase for 72 hr. Decreased levels in Ya and Yc and increases in Yp were detected by immunoblotting methods, indicating that translation products changed together with mRNA levels in the cultured cells. The appearance of Yp transcripts in hepatocytes was effectively blocked by addition of dexamethasone to the culture medium. Elevations of Yp levels are characteristic of the cell culture system and factors regulating Yp transcription in nodules and carcinomas may also be operative in cultured hepatocytes. PMID- 2912829 TI - Discrepancy between portal pressure and systemic hemodynamic changes after incremental doses of propranolol in awake portal hypertensive rats. AB - The effects of increasing doses of propranolol were studied in awake portal hypertensive rats in order to elucidate the relative effects of the beta-blocker on systemic and splanchnic circulation. Hemodynamic responses to 0.1, 0.2 and 0.4 mg per min infusions of propranolol were compared with placebo in awake rats with portal hypertension due to portal vein stenosis. Heart rate significantly and progressively decreased from 356 +/- 13 to 293 +/- 10 beats per min (mean +/- S.E.). Cardiac output significantly decreased from 54 +/- 3 to 42 +/- 3 ml per min per 100 gm body weight at the highest dose. Significant decrease in portal tributary blood flow from 27 +/- 1 to 18 +/- 1 ml per min, at 0.4 mg per min dose, was due not only to the decrease in cardiac output but also to a significant increase in portal tributary vascular resistance from 269 +/- 17 to 368 +/- 31 dyne per sec per cm5 x 10(3). However, portal pressure showed only an insignificant decrease from 14.9 +/- 1.1 to 14.1 +/- 1.4 mmHg. The reduction in portal pressure being minimal, in spite of a significant decrease in portal tributary blood flow, is explained by an increase in combined hepatic and collateral resistance from 44 +/- 2 to 66 +/- 4 dyne per sec per cm5 x 10(3), p less than 0.05, at 0.4 mg per min dose. We conclude that the systemic and splanchnic effects of propranolol show discrepancy at two levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2912830 TI - Incomplete compensation of enhanced hepatic oxygen consumption in rats with alcoholic centrilobular liver necrosis. AB - Centrilobular hypoxia mediated by enhanced hepatic consumption of oxygen has been hypothesized to be a factor of pathogenetic importance in ethanol-induced liver injury. In the present study, this hypothesis was tested in a rat model which developed alcoholic centrilobular liver necrosis. Male Wistar rats were infused with high fat diet plus ethanol or isocaloric glucose for 7 weeks, a duration which resulted in induction of balloon cell degeneration, focal necrosis, and inflammation in the centrilobular region of the liver of the ethanol-fed animals. Hepatic blood flow, oxygen consumption and oxygen delivery were determined by the radiolabeled microsphere method and measurement of oxygen content in arterial, portal venous, and hepatic venous blood. Hepatic oxygen consumption was markedly increased by 159% in the ethanol-fed animals compared to that in the controls when results were expressed as relative to body weight. Even after these results were standardized per gram of liver weight, hepatic oxygen consumption was still significantly elevated in the ethanol-fed group, but the magnitude of the elevation was reduced to 70%, due to marked hepatomegaly observed in these animals. There was a concomitant 59% increase in hepatic oxygen delivery in the ethanol-fed rats when expressed per kilogram of body weight, and this effect was attributable entirely to increased portal blood flow. However, the increment of this increase in oxygen delivery was much too small to compensate for the 159% increase in oxygen consumption. In addition, this increase in hepatic oxygen delivery was no longer observable when the results were reexpressed based on the liver weight.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2912831 TI - The pre-S2 region of hepatitis B virus: more questions than answers. PMID- 2912832 TI - Relapsing or reinfectious lyme hepatitis. PMID- 2912833 TI - The nonspecificity of electroencephalographic triphasic waves: the emperor defrocked. PMID- 2912834 TI - Gluconeogenesis from nitrogen precursors and hyperammonemia of cirrhosis: is there a cause-effect relationship? PMID- 2912835 TI - C4 function in children with autoimmune chronic active hepatitis. PMID- 2912836 TI - Protecting child witnesses in sexual abuse cases. PMID- 2912837 TI - Elderly widow develops panic attacks, followed by depression. PMID- 2912838 TI - Developing local resources to enrich the practice of rural community psychology. PMID- 2912839 TI - Staff injuries from inpatient violence. AB - A one-year study of staff injuries from inpatient violence at a large forensic state hospital found that 121 staff members sustained 135 injuries. Nursing staff sustained 120 of the injuries, for a rate of 16 injuries per 100 staff, and professional staff sustained three injuries, for a rate of 1.9 injuries per 100 staff. The majority of injuries to nursing staff (9.9 per 100 staff) were sustained while containing patient violence, and the rest were the result of assault (6.1 per 100 staff). Male nursing staff were nearly twice as likely as female staff to be injured and nearly three times as likely to receive containment-related injuries. The highest rates of injury were noted among ward nursing leadership. Injuries by assault were more likely than containment-related injuries to be head injuries, to cause more than three weeks' absence from work, and to affect more recently hired staff. The usefulness of the methodology in analyzing patterns of staff injury from inpatient violence is discussed. PMID- 2912840 TI - State hospitals as acute care facilities. PMID- 2912841 TI - Use of electroconvulsive therapy at a university hospital: 1970 and 1980-81. AB - The use of electroconvulsive therapy (ECT) at a university teaching hospital in 1970 and in 1980-81 was reviewed. The percentage of psychiatric patients who received ECT declined modestly over the period, from 4.4 percent to 2.9 percent, despite compelling evidence of its safety and efficacy. Its use as a first-line treatment appeared to drop markedly in 1980-81, however, as indicated by a significantly longer mean period of hospitalization before administration of ECT. Overall length of hospitalization was significantly longer for patients who received ECT in 1980-81. These patients were also more likely to have had previous psychiatric admissions, suggesting they may have been more seriously ill. The findings are compared with use of ECT in other settings. PMID- 2912842 TI - Policing sexuality in a modern state hospital. AB - In 1985 a grand jury was convened by the district attorney to investigate conditions at the Rochester (N.Y.) Psychiatric Center following the center's decision not to notify police of the sodomy of a patient by another patient. The grand jury brought no civil or criminal indictments, but the incident touched off a wave of negative publicity about the hospital and prompted local police and the district attorney to demand that the hospital report any incident of sexual activity involving a mentally incompetent patient. As a result, the hospital instituted a stringent policy requiring extensive investigation and physical examination of patients found having sex. This article discusses legal and clinical issues that were raised by the incident, the impact of public scrutiny on the policing of patient sexuality. The negative aspects of overreporting sexual activity at a state hospital are described. PMID- 2912843 TI - Medical disorders associated with psychiatric comorbidity and prolonged hospital stay. PMID- 2912845 TI - PTSD in minorities. PMID- 2912844 TI - Compliance with less restrictive aggression-control procedures. PMID- 2912846 TI - Dice therapy. PMID- 2912847 TI - The medically indigent mentally ill: approaches to financing. PMID- 2912848 TI - Execs: government ignores duty to help the poor. PMID- 2912849 TI - Gains outweigh costs of quicker bill collection. PMID- 2912850 TI - Jittery investors may chill low-end capital market. PMID- 2912851 TI - Quality--thy name is nursing care, CEOs say. PMID- 2912852 TI - New process lets hospital make hips that fit. PMID- 2912853 TI - 'Underautomated' medical records clog system. PMID- 2912854 TI - PROs: peering harder in the '90s. PMID- 2912855 TI - Marketing to seniors: time, attention, and TLC. PMID- 2912856 TI - CEO advice on consultants: buy wisely; use well. PMID- 2912857 TI - Home i.v. market is healthy hospital option. PMID- 2912858 TI - National, state efforts address nurse shortage. PMID- 2912859 TI - CRNA rates linked to surgical access. PMID- 2912860 TI - 'You don't find many patients in in-boxes'. Interview by Alden Solovy. PMID- 2912861 TI - Private sector courts low-cost subacute care. PMID- 2912862 TI - Hospitals, unions preparing for labor showdown. PMID- 2912863 TI - PPOs join forces for economy, market leverage. PMID- 2912864 TI - Critics seek changes in nursing home survey. PMID- 2912865 TI - While some indices level, patient margin slips. PMID- 2912866 TI - Study finds bedside terminals prove their worth. PMID- 2912867 TI - Leave out the glitz; conservative wins the job. PMID- 2912868 TI - The next generation of health care quality. PMID- 2912869 TI - Considering dementia. PMID- 2912870 TI - Lymphocytic ("microscopic") colitis: a comparative histopathologic study with particular reference to collagenous colitis. AB - Lymphocytic colitis, previously termed "microscopic colitis", is a clinicopathologic syndrome of watery diarrhea, grossly normal colonoscopy, and mucosal inflammatory changes. Since lymphocytic colitis is a new, incompletely characterized entity, a histopathologic study was performed to compare lymphocytic colitis (n = 16), collagenous colitis (n = 17), idiopathic inflammatory bowel disease (n = 16), acute colitis (n = 16), and histologically normal colon (n = 12). The study was a blinded semiquantitative analysis of histologic features in the surface epithelium, lamina propria, and crypts. The most distinctive feature of lymphocytic colitis was increased intraepithelial lymphocytes, particularly in the surface epithelium (P = .0001 v idiopathic inflammatory bowel disease, acute colitis, and normal colon). Other prominent features of lymphocytic colitis included surface epithelial damage (P less than .005 v idiopathic inflammatory bowel disease and normal colon), increased lamina propria chronic inflammation (P less than .01 v normal), and minimal crypt distortion or active cryptitis. There were striking similarities between lymphocytic colitis and collagenous colitis, but subepithelial collagen thickening was seen only in collagenous colitis. Idiopathic inflammatory bowel disease showed prominent crypt distortion and greater active inflammation, in addition to minimal intraepithelial lymphocytes. Acute colitis occasionally demonstrated prominent surface epithelial damage, but was otherwise dissimilar from lymphocytic colitis. We reached the following conclusions: (1) the entity "microscopic colitis" shows characteristic histopathology including prominent lymphocytic infiltration of epithelium, and thus, a more appropriate designation is lymphocytic colitis; (2) although lymphocytic colitis closely resembles collagenous colitis, each entity is distinct on biopsy; and (3) lymphocytic colitis is readily distinguishable from idiopathic inflammatory bowel disease, acute forms of colitis, and normal colorectum. PMID- 2912871 TI - Paragangliomas: assessment of prognosis by histologic, immunohistochemical, and ultrastructural techniques. AB - To predict clinical outcome, we studied 42 paragangliomas from 37 patients by routine histology, immunohistochemistry, and electron microscopy. A panel of antisera to neuron-specific enolase (NSE), chromogranin, and met-enkephalin was used to identify chief (type I) cells, and S-100 protein and glial fibrillary acid protein (GFAP) sustentacular (type II) cells. The intensity of staining of type I cells and the density of type II cells were assessed semiquantitatively (0 to 4+) in a total of 38 tumors. A total of 23 of 24 low-grade tumors (solitary, multiple, or associated with other neoplasms; 95.8%) contained type II cells immunoreactive with either S-100 protein or GFAP, and all were positive when S 100 protein and GFAP were used in combination. Five of the nine intermediate grade (recurrent and/or locally aggressive) tumors were identified as glomus jugulare tumors (GJT). Three intermediate-grade GJTs were devoid of GFAP-reactive type II cells and four GJTs were negative for S-100 protein. Type II cells were identified in only one of five high-grade (malignant) paragangliomas and that tumor contained vanishingly rare cells that were weakly S-100 protein positive but GFAP negative. Sustentacular cell density and chief cell staining intensity were both inversely related to tumor grade. The most sensitive chief cell marker was NSE (92.1%), followed by chromogranin (84.2%). The least sensitive (73.0%) and specific marker was met-enkephalin. Combinations of NSE or chromogranin with met-enkephalin identified chief cells in all cases. Electron microscopy identified neurosecretory granule-containing chief cells, but was of less value in delineating sustentacular cells because of their scarcity and the absence of specific features. By comparison, immunohistochemistry was superior in identifying sustentacular cells. The use of an immunohistochemical panel, in addition to routine histology, can confirm the diagnosis of a paraganglioma and can give an indication of the likely prognosis for a patient. PMID- 2912872 TI - The issues in autologous transfusion. AB - Autologous transfusion should be recognized by patients and physicians as an important measure to provide safer transfusion therapy. This should be suggested to patients in general good health (who are not obviously frail) who have no significant medical problems and no likelihood of severe reaction, who can take iron supplements, and who have at least a 10% chance of using blood during surgery or are having surgery in which the average use is one or more units. Such patients should receive iron supplementation beginning 1 week before the first autologous donation, and should donate one to five units on a weekly basis, but no more frequently than every 72 hours, with their last unit donated 72 hours before surgery. Elderly individuals may donate if the risk of donor reaction seems low. In children and adults, the amount of blood removed should be reduced in proportion to the blood volume if the individual does not meet the standard weight of 50 kg for a 450-mL donation. "Fail-safe" identification systems should be used; these will insure that the correct donor/patient receives the transfusion. Processing of the units is preferred but still optional. Use of these units as homologous units should not be done unless the donor has a hematocrit level acceptable to an autologous donor, meets all the criteria for recipient safety, the unit is processed and negative for all viral markers, and the donor has recently (eg, within 3 years) participated in the volunteer donor program. The unit should be transfused to the patient in situations in which homologous blood would be indicated. Safeguards to prevent volume overload are needed when the unit is stored as whole blood. Future research objectives should include the use of recombinant erythropoietin to prevent donation-induced anemia, delineation of medical conditions which should contraindicate the donation, and determination of the real costs involved in autologous transfusion. Education of the general public, patients, and physicians about the desirability of autologous transfusion should proceed. Third-party carriers also need to be educated about the cost implications and the need to pay for this activity. However, such education should also stress that autologous units will only cover planned, elective surgery and that major blood needs for emergency surgery, trauma, and chronic transfusion will still need to be met by homologous blood from altruistic community blood donors. PMID- 2912873 TI - Granulomatous mastitis caused by histoplasma and mimicking inflammatory breast carcinoma. AB - Two cases of a lobular, necrotizing granulomatous process causing a unilateral painful breast mass mimicking carcinoma are presented for comparison. While the morphologic appearance in each case was that of lobular granulomatous mastitis, the etiologic agent in one case appeared to be Histoplasma capsulatum, based on Grocott methenamine silver staining, and represents the second reported case of histoplasmosis involving only breast parenchyma. Awareness of the rare entity, granulomatous mastitis, is important for the pathologist because the definitive diagnosis is made microscopically. Thorough evaluation of the breast tissue is essential for its management and should eventually contribute to the clarification of its etiology. PMID- 2912874 TI - Immunohistochemical distinction of malignant mesothelioma from pulmonary adenocarcinoma with anti-surfactant apoprotein, anti-Lewisa, and anti-Tn antibodies. AB - Nine cases of malignant mesothelioma of pure epithelial and biphasic types (five pleural, three peritoneal, and one pericardial mesotheliomas), seven cases of benign adenomatoid tumor of the uterus, and 21 cases of peripheral pulmonary adenocarcinoma of non-mucus-producing type were examined immunohistochemically for expression of keratin, vimentin, carcinoembryonic antigen (CEA), surfactant apoprotein, Lewis blood group antigens, and Tn antigen. The majority (78%) of the malignant mesotheliomas expressed keratin, but CEA and surfactant apoprotein were not detected in any mesotheliomas. On the other hand, pulmonary adenocarcinomas expressed not only keratin (100%), but also CEA (62%) and surfactant apoprotein (62%). The expression of Lewisa blood group antigen and Tn antigen was detected in 76% and 62% of the pulmonary adenocarcinomas, respectively, but only one mesothelioma was stained for Lewisa antigen. This study reveals that the majority of malignant mesotheliomas can be distinguished from pulmonary adenocarcinomas by immunohistochemcial staining for CEA, surfactant apoprotein, Lewisa antigen, and Tn antigen. Immunohistochemically, adenomatoid tumors behaved similarly to malignant mesotheliomas. PMID- 2912875 TI - Nodular proliferation of calcifying connective tissue in the rete testis: a study of three cases. AB - We report the first description of a bilateral rete testis lesion. The lesion was found in three adult men with histories of myocardium infarct or hemorrhage. The histologic study of the rete testis in these men revealed nodular sessile or pediculate formations which protruded into the rete testis channels. These polypoid formations consisted of an axis of connective tissue covered by a flattened epithelium. The axis contained a variable number of fibroblasts, areas with fibrin-like material, and small to large calcium deposits. Inflammatory infiltrates were neither observed in the rete testis nor in the testicular parenchyma. The testicular pattern varied from seminiferous tubules with complete spermatogenesis (two cases) to tubules with Sertoli cells and a few spermatogonia, surrounded by a thickened tunica propia. The term "nodular proliferation of calcifying connective tissue in the rete testis" is proposed to designate this lesion. PMID- 2912876 TI - Unexpected splenic nodules in leukemic patients. AB - We reviewed a series of five splenectomy specimens from patients with various leukemias (three cases of chronic myelocytic leukemia, one case of acute myelocytic leukemia, and one case of hairy cell leukemia). In addition to diffuse red pulp disease, we unexpectedly encountered nodules grossly in each of the specimens. These represented sea blue histiocytosis (one case), focal hairy cell leukemia (one case), localized blast transformation (one case), and concentrated foci of treated leukemia (two cases), with a prominence of immature granulocytic precursors on a background of trilineage hyperplasia. These cases are reported because they are unusual and because they furnish interesting correlates of gross and microscopic anatomy. PMID- 2912877 TI - Distinction between metastatic melanoma and primary parotid gland carcinoma using monoclonal HMB 45 antimelanoma antibody: report of a case. AB - A case of malignant melanoma primary of the facial skin presenting with pre auricular and submandibular masses, both thought to be metastatic melanoma, is reported. The case illustrates the practical application of a recently developed and commercially available specific anti-melanoma monoclonal antibody, HMB 45, which is useful in distinguishing between metastatic melanoma to a submaxillary lymph node and a synchronous primary parotid, poorly differentiated adenocarcinoma. The value of specific anti-melanoma antibody in conjunction with an antibody panel that includes S100, keratin, and epithelial membrane antigen in the distinction of melanomas from anaplastic carcinomas is discussed. PMID- 2912878 TI - Leiomyoma of the uterus with multiple extrauterine smooth muscle tumors: a case report suggesting multifocal origin. AB - A 17-year-old woman underwent hysterectomy for removal of a "mitotically active" (six to seven mitoses per 10 high-power fields) yet otherwise benign-appearing cellular smooth muscle tumor. Eleven years later, she developed multiple histologically benign smooth muscle tumors in the posterior mediastinum, deep soft tissues of the neck, paravertebral region, incisional scar, and mesentery. The distribution and histologic appearance of the tumors, as well as the protracted clinical course, suggest multifocal origin rather than widespread metastases from a low-grade uterine leiomyosarcoma. This case raises the possibility that some similar cases reported as so-called benign metastasizing leiomyoma may be more satisfactorily explained by the concept of multifocality. PMID- 2912879 TI - Simultaneous occurrence of medullary and follicular carcinoma in the same thyroid lobe. AB - A rare case of the simultaneous development of medullary and follicular carcinoma of the thyroid gland in a 51-year-old Japanese woman is examined. A preoperative diagnosis was made by needle aspiration cytology. Neoplastic cells of the medullary carcinoma were positive for calcitonin and carcinoembryonic antigen, whereas the tumor cells of the follicular carcinoma were negative for these substances. This case presents evidence that, in rare cases, two malignant epithelial neoplasms of different origins can occur in the same lobe of the thyroid. PMID- 2912880 TI - More on AIDS autopsies: the importance of compliance with universal precautions. PMID- 2912881 TI - A genetic and anthropological study of atlanto-occipital fusion. AB - Families of 20 probands with atlanto-occipital fusion were studied, and the neurological complications in these patients described. In X-ray studies of 115 close relatives, 4 additional cases (3.5%) with the same anomaly were detected. In a comparison of adult patients with closely related age- and sex-matched controls, all anthropological measurements except length and breadth of the head tended to be smaller in the patients; for height, weight, leg and foot length, and the robusticity index, these differences were statistically significant. PMID- 2912882 TI - Hypohidrotic ectodermal dysplasia. Clinical study of a family of 30 over three generations. AB - A family carrying the X-linked gene for hypohidrotic ectodermal dysplasia (hereditary ectodermal polydysplasia or Christ-Siemens-Touraine syndrome) over three generations was monitored for more than 15 years. Two prenatal diagnoses were carried out by fetoscopy on skin biopsies. Polymorphic probes were used in the segregation analysis of the Xq11-21 region carried out on 30 members of the family. Current screening possibilities for the carriers and prenatal diagnosis are discussed. PMID- 2912883 TI - Centromeric association of a microchromosome. A new category of non-random arrangement of metaphase chromosomes. AB - A supernumerary microchromosome measuring 0.5-1 microns found in over half of the metaphases of a CREST scleroderma patient and his daughter has been characterized by various cytogenetic techniques. The microchromosome consisted of constitutive heterochromatin and contained nuclear antigens reacting with specific anti kinetochore antibodies. The most remarkable property of the microchromosome was its non-random position: it was closely associated with the centromere of any of the normal chromosomes in the majority of the metaphases. Furthermore, an inordinately high rate of Y chromosome aneuploidy was found in the CREST scleroderma patient. The origin and structure of the microchromosome, its possible connection with the CREST variant of scleroderma, and the phenomenon of centromeric association are discussed. PMID- 2912884 TI - Localization of Y chromosome sequences and X chromosomal replication studies in XX males. AB - By in situ hybridization, Y-specific DNA sequences were localized on Xp22.3-Xpter of one of the two X chromosomes in all of eleven XX males studied. In nine of the cases the presence of the Y-specific DNA did not affect random X inactivation in fibroblasts. Fibroblasts of the other two cases showed a preferential inactivation of the Y DNA-carrying X chromosome. In only one of these two exceptions blood lymphocytes could also be studied, and here, random inactivation of the Y DNA-carrying X chromosome occurred. Furthermore, the gene dosage of steroid sulfatase (STS) was examined by Southern blot analysis. In ten of the cases including the one showing random X-inactivation in lymphocytes but not in fibroblasts, a double dosage of the STS gene is present. The remaining case with non-random inactivation shows a single STS gene dosage. This case was reported previously to have STS enzyme activity in the male range. It is assumed that, as a consequence DNA sequences may result in the preferential inactivation of the Y DNA-carrying X chromosome. PMID- 2912885 TI - Chromosomal assignment of a glutamic acid transfer RNA (tRNAGlu) gene to 1p36. AB - A gene for tRNAGlu has been assigned to human chromosome 1p36 by in situ hybridisation using a [3H]-labelled or biotinylated 2.4-kb (human) DNA fragment containing a tRNAGlu gene as a probe. With the biotinylated DNA probe a secondary statistically significant site of hybridisation was observed at 1q21-22 which might represent a pseudogene or related sequence. In fibroblasts from gorilla (Gorilla gorilla) using biotin labelling, a single site of hybridisation occurred at 1qter which provides further support for homology of 1q in the higher apes and human 1p. PMID- 2912886 TI - Chronic nonspherocytic hemolytic anemia (CNSHA) and glucose 6 phosphate dehydrogenase (G6PD) deficiency in a patient with familial amyloidotic polyneuropathy (FAP). Molecular study of a new variant (G6PD Clinic) with markedly acidic pH optimum. AB - A new glucose-6-phosphate dehydrogenase (G6PD) variant with severe erythrocytic G6PD deficiency and a unique pH optimum is described in a young patient with chronic nonspherocytic hemolytic anemia (CNSHA) and familial amyloidotic polyneuropathy (FAP). Chronic hemolysis was present in the absence of infections, oxidant drugs or ingestion of faba beans. Residual enzyme activity was about 2.6% and 63% of normal activity in erythrocytes and leucocytes, respectively. A molecular study using standard methods showed G6PD in the patient to have normal electrophoretic mobility (at pH 7.0, 8.0 and 8.8), normal apparent affinity for substrates (Km, G6P and NADP) and a slightly abnormal utilization of substrate analogues (decreased deamino-NADP and increased 2-deoxyglucose-6-phosphate utilization). Heat stability was found to be markedly decreased (8% of residual activity after 20 min of incubation at 46 degrees C) and a particular characteristic of this enzyme was a biphasic pH curve with a greatly increased activity at low pH. Although molecular characteristics of this variant closely resemble those of G6PD Bangkok and G6PD Duarte, it can be distinguished from these and all other previously reported variants by virtue of its unusual pH curve. Therefore the present variant has been designated G6PD Clinic to distinguish it from other G6PD variants previously described. PMID- 2912887 TI - Erythrocyte acid phosphatase (ACP1) activity. In vitro modulation by adenosine and inosine and effects of adenosine deaminase (ADA) polymorphism. AB - Erythrocyte acid phosphatase (ACP1) activity was determined in the absence of modulators and in the presence of either adenosine or inosine as modulators in 154 samples of red blood cells collected from adult donors. Adenosine and inosine showed modulating effects (activation), that were genotype dependent in the allele order pb less than pa less than pc; the activation by inosine was much higher than by adenosine. The modulating effect was dependent on adenosine deaminase (ADA) genotype: In carriers of ADA2 allele the activation with ACP1 phenotype A was lower and that with phenotypes CA and CB was higher than in ADA1/ADA1 subjects. In addition, the basic ACP1 activity (i.e., without modulators) also appeared to be dependent on ADA genotype: The lowest ACP1 activity was observed in A and BA subjects carrying the ADA2 allele. Since the deamination of adenosine to inosine associated with ADA2-1 phenotype is slower than that associated with ADA1, the interaction of ADA on ACP1 activity may in fact be explained by a lower intracellular concentration of inosine in ADA2 carriers and, therefore, by a lower modulating effect of this on acid phosphatase activity. PMID- 2912888 TI - Sublocalization of the human protein C gene on chromosome 2q13-q14. AB - The localization of human protein C gene on chromosome 2 was investigated by in situ hybridization using a partial cDNA for protein C. Silver-grain analysis indicates that the protein C gene is located on 2q13-q14. PMID- 2912889 TI - Detection of Duchenne muscular dystrophy carriers by dosage analysis using the DMD cDNA clone 8. AB - Deletion screening in 11 unrelated DMD patients has been performed using DMD cDNA clones 1-8. Of these 11 patients, 6 exhibit deletions of the cDNA clone 8. The carriership of 18 female relatives from these six DMD families has been investigated by dosage analysis. It is shown that dosage analysis is an available method to determine the carrier status of the female relatives of DMD patients showing a deletion within a DMD cDNA clone. PMID- 2912890 TI - Familial transmission of 16p trisomy in an infant. AB - Based on four reported cases including the present case, 16p trisomic infants have remarkably similar features. These are severe developmental delay, psychomotor retardation, typical facies, and anomalies of extremities. PMID- 2912891 TI - A new rare PGD variant, PGD Mediterranean. AB - The authors report a rare slow PGD variant observed in seven individuals in different Israeli population groups. PMID- 2912892 TI - Recombination between DXS7, DXS84 and a rare form of X-linked retinitis pigmentosa (McK-30320). PMID- 2912893 TI - Isolation of a corncob (coaggregation) receptor polypeptide from Fusobacterium nucleatum. AB - Corncobs, which are distinct morphological units formed by the ordered coaggregation of a filamentous microorganism and streptococci, can be made in vitro by using oral strains of Fusobacterium nucleatum and Streptococcus sanguis. Previous studies have shown that strains of F. nucleatum contain one of at least two different types of corncob receptor. The objective of this study was to isolate the receptor from F. nucleatum ATCC 10953 as the first step in the elucidation of the molecular basis of corncob formation. The cell envelope fraction from this bacterium was treated with trypsin, delipidated with chloroform-methanol, and subjected to ion-exchange chromatography. A single polypeptide (apparent Mr, 39,500), which was eluted from the column with 0.5 M sodium chloride and extracted with dodecyltrimethylammonium bromide to remove contaminating lipopolysaccharide, inhibited corncob formation between strain ATCC 10953 and S. sanguis CC5A. Similarly derived cell fractions from either F. nucleatum FDC 364 or Fusobacterium necrophorum failed to effect coaggregation in the inhibition assay. Amino acid analysis of the polypeptide showed a moderately hydrophobic character (polarity index, 41) and 11% basic residues. Antiserum made against the purified polypeptide agglutinated F. nucleatum ATCC 10953, neutralized the ability of this bacterium to form corncobs, and agglutinated whole cells of S. sanguis CC5A that were precoated with the receptor polypeptide. The identification and isolation of this receptor should greatly enhance our ability to define some of the complex intergeneric coaggregation mechanisms that are thought to occur in the human oral cavity. PMID- 2912894 TI - Impaired antipneumococcal activity of bronchoalveolar lining material of neonatal rats. AB - Pulmonary clearance of inhaled pneumococci is markedly impaired in neonatal rats compared with that in adult rats. To determine whether this impairment is due to a deficiency of extracellular bactericidal factors, the antipneumococcal activity of free fatty acids (FFA) in lung surfactant and the levels of lysozyme and transferrin in lavage fluids were quantified. Surfactant from adult rats averaged 68 U of antipneumococcal activity per g (dry weight) of lung, compared with less than 0.25 U for rats less than 1 week old (P less than 0.001). The kinds of FFA in surfactant of neonatal and adult rats were essentially identical, and the antipneumococcal activity of highly purified FFA from surfactant of neonatal and adult rats was also the same. However, the quantity of FFA in surfactant varied significantly with age, and rats less than 3 weeks old had much lower levels of surfactant FFA than did adults (P less than 0.001). In addition, lavage fluids from neonatal rats inhibited the antipneumococcal activity of surfactant FFA more than lavage fluids from adults did (P less than 0.02). This inhibitory activity did not appear to be due to protein binding. Lavage fluids from neonates showed an age-related deficiency of lysozyme (P less than 0.001), but lysozyme appeared to play no role in pneumococcal killing by the surfactant fraction of lavage fluids in vitro. Transferrin levels in lavage fluids were similar for neonates and adults. It was concluded that lung surfactant from neonatal rats was deficient in antipneumococcal activity, due mostly to low levels of FFA and to a lesser degree to increased levels of inhibitor(s) in lavage fluids. PMID- 2912895 TI - Somnogenic activities of synthetic lipid A. AB - Bacterial infections and various immune response modifiers, including endotoxin and its lipid A moiety, alter sleep duration. The purpose of this study is to amplify our understanding of lipid A structure-somnogenic-pyrogenic activity relationships. Four synthetic disaccharide analogs of lipid A (LA-15-PP, LA-15 PH, LA-16-PH, and LA-18-PP) and a biosynthetic monosaccharide analog of lipid A (lipid X) were tested in rabbits for their effects on slow-wave sleep, rapid-eye movement sleep, electroencephalographic slow-wave (0.5- to 4.0-Hz) amplitudes, and brain-colonic temperatures. Substances were injected intravenously and intracerebroventricularly. Compound LA-15-PP was the most potent; it significantly increased slow-wave sleep, delta electroencephalographic amplitudes, and brain-colonic temperatures while reducing rapid-eye-movement sleep. Compound LA-15-PH (monophosphoryl analog of LA-15-PP) induced effects similar to those of LA-15-PP, although the responses were weaker. Compound LA-18 PP induced increases in slow-wave sleep and delta amplitudes only after high doses, whereas compound LA-16-PH was devoid of these activities at the doses tested. Intracerebroventricular, but not intravenous, injections of lipid X induced small but significant increases in both slow-wave sleep and rapid-eye movement sleep without affecting delta amplitudes or brain-colonic temperatures. These data suggest that the somnogenic actions of these lipid A analogs depend on the acylation or phosphorylation pattern and backbone structures of the molecules. Their soporific activities parallel their relative behaviors in other biological assays. PMID- 2912896 TI - Human immune response to Vibrio cholerae O1 whole cells and isolated outer membrane antigens. AB - The serum immunoglobulin G (IgG) and mucosal secretory IgA (SIgA) response of human volunteers challenged with Vibrio cholerae O1 was analyzed for reactivity to V. cholerae O1 antigens by the immunoblot technique. Components of both in vitro- and in vivo (rabbit ligated ileal loop)-grown V. cholerae O1 were separated by sodium dodecyl sulfate-urea-polyacrylamide gel electrophoresis. Postchallenge serum IgG reacted uniquely with 15 antigens and with greater intensity than did prechallenge serum with at least 16 antigens. Serum IgG and SIgA reacted with antigens present in preparations from the homologous challenge strain of V. cholerae as well as antigens from strains of heterologous biotype or serotype. These heterologous antigens may represent antigens responsible for protection to rechallenge with a heterologous strain of V. cholerae. All the antigens detected by postchallenge jejunal fluid SIgA had an apparent molecular size of less than 25 kilodaltons. Serum IgG and jejunal fluid SIgA also reacted with antigens unique to in vivo-grown cells and several antigens in outer membrane preparations, suggesting that studies of protective immunity and V. cholerae O1 pathogenesis should include examination of both in vitro- and in vivo grown V. cholerae O1 cellular antigens. PMID- 2912897 TI - Effects of Histoplasma capsulatum on murine macrophage functions: inhibition of macrophage priming, oxidative burst, and antifungal activities. AB - Histoplasma capsulatum yeast cells fail to trigger an oxidative burst response in normal murine macrophages. The results of this study, in which an in vitro assay of macrophage antifungal effects was used, extend these findings. During 18 h of incubation, unprimed elicited murine macrophages inhibited H. capsulatum growth only when macrophages were present in great excess. Gamma interferon (IFN-gamma) primed macrophages showed enhanced fungal growth inhibition but a similar requirement for an excess of phagocytes. Macrophages containing heat-killed H. capsulatum exhibited diminished antifungal effects toward viable H. capsulatum and Saccharomyces cerevisiae cells. Parallel experiments showed no comparable effect of ingested latex particles on macrophage antifungal activity. Using chemiluminescence as a measure of the oxidative burst, we found that macrophages primed in vitro with IFN-gamma alone failed to exhibit a significant response to triggering by H. capsulatum yeast cells unless a second priming agent (tumor necrosis factor alpha or bacterial lipopolysaccharide) was added to IFN-gamma. Furthermore, macrophage priming with single agents was blocked by the prior ingestion of heat-killed H. capsulatum. These studies provide evidence that ingestion of H. capsulatum yeast cells can induce a prompt and enduring deactivation of murine macrophages. PMID- 2912898 TI - Purification, location, and immunological characterization of the iron-regulated high-molecular-weight proteins of the highly pathogenic yersiniae. AB - We have previously shown that under iron limitation, different Yersinia species synthesize new polypeptides. Two of them, the high-molecular-weight proteins (HMWPs), are expressed only by the highly pathogenic strains. In the present study, the HMWPs from Y. enterocolitica serovar O:8 were purified by gel filtration, and specific antibodies were obtained. Using these antibodies, we show that the two polypeptides were synthesized de novo during iron starvation and that they were found essentially in the bacterial outer membrane fractions, although the majority of the molecules were not exposed on the cell surface. We also demonstrate that the two proteins had common epitopes and that the HMWPs of the high-virulence-phenotype species Y. pestis, Y. pseudotuberculosis, and Y. enterocolitica serovar O:8 (a strain different from the one used to purify the proteins) are antigenically related. The less pathogenic and nonpathogenic strains did not exhibit cross-reacting material, suggesting that these strains do not synthesize even an altered form of the HMWPs. PMID- 2912899 TI - Antibodies raised against synthetic peptides from the Arg-Gly-Asp-containing region of the Leishmania surface protein gp63 cross-react with human C3 and interfere with gp63-mediated binding to macrophages. AB - The Leishmania surface glycoprotein gp63 binds to complement receptor type 3 on the macrophage surface. Antibody raised against a synthetic peptide containing the Arg-Gly-Asp region of the amino acid sequence of gp63 recognizes both gp63 and the alpha-chain of human C3. Monovalent Fab fragments from this antibody block gp63-mediated binding to macrophages. PMID- 2912900 TI - Immunoglobulin-binding activity among pathogenic and carrier isolates of Haemophilus somnus. AB - Nonimmune binding of immunoglobulin to whole bacteria was quantitated for North American isolates of Haemophilus somnus recovered from cattle with pneumonia, reproductive failure (abortion), or thromboembolic meningoencephalitis or from the vagina or prepuce of carrier cattle. Quantitative binding activity covered a wide range, with most pathogenic and carrier isolates demonstrating significant immunoglobulin-Fc binding. Isolates for which Fc binding was not detectable were recovered only from the prepuces of asymptomatic bulls. Expression of Fc-binding activity correlated with the presence of the 41,000-molecular-weight protein (41K protein) and 270K protein. Isolates that lacked Fc-binding activity did not possess 41K or 270K protein. A 33K protein was detected in isolates that lacked Fc-binding activity but not in isolates that bound Fc. PMID- 2912901 TI - Ceruloplasmin can substitute for rabbit serum in stimulating the growth of Treponema denticola. AB - The growth of Treponema denticola in a complex medium was stimulated by human ceruloplasmin and, to a lesser extent, albumin, alpha-1-antitrypsin, alpha-1-acid glycoprotein, and alpha-2-macroglobulin. Human ceruloplasmin could stimulate growth of T. denticola as well as or better than 5% rabbit serum, with a dose response relationship of between 1 and 5 mg of ceruloplasmin per ml of culture medium. These results suggest that ceruloplasmin could substitute for rabbit serum in stimulating the growth of T. denticola. PMID- 2912902 TI - Citrobacter freundii produces an 18-amino-acid heat-stable enterotoxin identical to the 18-amino-acid Escherichia coli heat-stable enterotoxin (ST Ia). AB - We purified and sequenced the heat-stable enterotoxin produced by Citrobacter freundii. The toxin was detected during purification by reaction with monoclonal antibody to Escherichia coli heat-stable enterotoxin. The C. freundii toxin amino acid sequence was identical to that of the 18-amino-acid heat-stable enterotoxin (STa) produced by toxigenic E. coli. PMID- 2912903 TI - The heterogeneous group for chronically physically ill and physically healthy but emotionally disturbed children and adolescents. AB - The homogeneous group has been the most common form of group therapy for chronically physically ill children and adolescents. The goals of these groups have included the provision of peer support, adaptation to the realities of physical illness, and acceptance of and cooperation with the medical management of the disease. The refinement of the theory of developmental ego psychology suggests that the heterogeneous group has potential for aiding the emotional maturation of the chronically physically ill. This paper presents examples of groups of latency-age children, early adolescents, and middle adolescents that included chronically physically ill with physically healthy peers. The groups were planned under the assumption that despite external differences, children and adolescents of a similar age identify with peers in terms of normal age-specific developmental needs and conflicts. PMID- 2912904 TI - Making society's groups more therapeutic. AB - This paper represents the author's Presidential Address to the American Group Psychotherapy Association, delivered at the annual meeting on February 11, 1988, in New York. The author poses a challenge: What can we teach society about how to make our groups more healing and productive? He suggests certain guidelines relating to effective communication, empathic understanding, willingness to assume responsibility, and, most importantly, recognition that groups exist for the individuals who comprise them. For groups to function well, individuals must play their role and sacrifice themselves for the good of the whole; yet for groups to function well, the needs of the individual must never be lost. PMID- 2912905 TI - Effect of depression on processing interactions in group psychotherapy. AB - Two studies were conducted to investigate the possibility of individual differences in the ability of inpatients to process interactions in group psychotherapy. The first was a pilot study conducted on groups of major depressive patients and matched normal subjects. Subjects were asked to give process comments after viewing simulations of typical group therapy interactions. These comments were later rated on the extent to which they reflected process qualities and accuracy. These data led to a more rigorous and extensive study that included more appropriate control groups as well as measures of potential confounding factors, such as simulation realism, verbal ability, and interaction comprehension. Results indicated that major depressives suffer from deficits in the ability to process group interactions, relative to three types of control groups, including normals. These differences in processing were not significantly positively correlated with any of the potential confounding factors. The implications for understanding interactional processing and group psychotherapy are discussed. PMID- 2912906 TI - Ultrastructural effects of sodium chloride on the corneal epithelium. AB - Ten excised rabbit corneas were bathed posteriorly with glutathione bicarbonate Ringers solution (GBR), while anteriorly the bathing solution was either GBR or sodium chloride solution (NaCl). All solutions had an osmolarity of 305 +/- 2 mOsm/kg. The corneas were fixed after 150 min exposure to the solutions, and prepared for electron microscopy. Morphometric analysis of the electron micrographs was conducted by an observer unaware of the anterior bathing solution. In each case, the epithelium was examined along a 1500 micron stretch of the basement membrane. Cells were categorized as normal, abnormal, and sloughing. Abnormal cells showed cytoplasmic and nuclear pallor, and disrupted cell membranes. Sloughing cells showed partial separation from the underlying epithelium. Corneas exposed to NaCl showed statistically significant differences from those exposed to GBR; the differences occurred in both the number of abnormal cells, and the number of sloughing cells. All observed ultrastructural changes were limited to the surface region of the epithelium. It is concluded that sodium chloride solution is inadequate at maintaining the epithelial surface. PMID- 2912908 TI - IgG and IgA antibody in tears of rabbits immunized by topical application of ovalbumin. AB - Rabbits were immunized by daily topical conjunctival application of ovalbumin. Control rabbits received ovalbumin intravitreally or intravenously. The direct plaque assay was used to detect IgM antibody-producing cells in lymph node, conjunctival, lacrimal gland and Peyer's patch tissues. A culture ELISA test was used to detect IgG and IgA antibody-producing cells. Serum and tears were tested for IgG antibody by ELISA and passive hemagglutination tests, and for IgA antibody by an ELISA assay. The conjunctival and cervical lymph node cells of topically immunized rabbits produced IgG and IgM antibodies. Neither IgG nor IgM antibody-producing cells were found in the Peyer's patches or lacrimal glands. Serum IgG antibody was detected by both ELISA and HA tests. IgG antibody was found (by the ELISA assay) in tears collected from most topically immunized rabbits, and from some intravitreally immunized rabbits, but not from the intravenously immunized animals. IgA antibody was found in tear samples collected after several weeks of daily topical immunization. IgA antibody-producing cells were detected in the conjunctival tissues, but not in the lymph nodes of those rabbits. PMID- 2912907 TI - Glucocorticoid-induced cataract in chick embryo monitored by Raman spectroscopy. AB - Glucocorticoid-induced cataract lens in chick embryo was monitored by laser Raman spectroscopy. The lens opacity that appeared in chick embryo is a reversible one. Raman spectra show no significant change in the relative content of water or secondary structure of the proteins upon lens opacification. The intensity ratios of tyrosine doublet bands in Raman spectra between clear and opaque lens portions are changes. This change is reversible, and is interpreted as a protein-water phase separation that occurred during lens opacification. PMID- 2912909 TI - Adaptation to telescopic spectacles: vestibulo-ocular reflex plasticity. AB - The vestibulo-ocular reflex (VOR) is a mechanism for the production of rapid compensatory eye movements during head movements. To investigate the adaptation of this reflex to spectacle magnifiers, the effect on the VOR of a brief period of wearing telescopic spectacles during head rotation was studied in normal subjects. VOR gain, as measured in darkness, was defined to be the ratio of compensatory slow phase eye velocity to head velocity. Initial VOR gain as measured for vertical axis sinusoidal head rotation at 0.1 Hz, amplitude 60 degrees/sec, was about 0.7. After 15 min adaptation by sinusoidal rotation during the viewing of a remote video display through X2, X4, or X6 binocular telescopic spectacles, 47-70% of subjects exhibited significant VOR gain increases of 7-46%. These increases were measured with occlusion of the unmagnified visual field peripheral to the telescopes during adaptation. There was considerable interindividual variability in adaptation to telescopic spectacles. Telescopic spectacle power had little or no effect on the amount of VOR change after adaptation, although all telescope powers produced a greater VOR gain change than did adaptation without telescopes. Testing of VOR gain at multiple frequencies indicated that adaptation to telescopic spectacles by rotation at a single sinusoidal frequency induces VOR gain changes across a broad spectrum of frequencies of head rotation. When the unmagnified peripheral visual field was unobstructed during adaptation, VOR gain increases were significantly less than when the unmagnified peripheral visual field was occluded, and were similar to those observed during adaptation without the wearing of telescopic spectacles at all. VOR gain adaptation was associated with amerlioration of symptoms of oscillopsia and motion discomfort initially experienced by about 20% of subjects wearing telescopic spectacles. PMID- 2912910 TI - Effects of selenium on ion homeostasis and transparency in cultured lenses. AB - Selenium toxicity was investigated in cultured rabbit lenses to provide further information about the role of Ca++ in Se cataract. At a dose of 0.1 mM for 20 hr, Se induces a 10% change in Na levels within 6 hr, a 30% increase after 20 hr, and a three-fold increase within 48 hr of subsequent culture after removal of Se. In contrast, Ca++ levels remained normal throughout the first 24 hr. Only a small, 25% decline in GSH was noted. Not until lenses begin to swell and become noticeably opaque and turbid were Ca++ levels found to be elevated. Thus, at 72 hr, 48 hr following the removal of selenium, Ca++ had increased to a concentration of 0.7 mM. Ca++ accumulation appears to be a consequence of osmotic stress rather than pump inhibition while Na accumulation is a direct consequence of Se-inhibited Na pump. PMID- 2912911 TI - Factors associated with visual outcome after photocoagulation for diabetic retinopathy. Diabetic Retinopathy Study Report #13. AB - Six risk factors for severe visual loss despite panretinal (scatter) photocoagulation were identified by analyzing data collected during the first 5 years after randomization in the Diabetic Retinopathy Study. Proportional hazards regression revealed NVD (neovascularization on/around the optic disc) to be the most important risk factor. The risk of severe visual loss rose with increasing NVD, hemorrhages/microaneurysms, retinal elevation, proteinuria, and hyperglycemia and fell with increasing "treatment density." These results are similar to previous DRS findings on untreated eyes. The importance of "treatment density" as an independent predictor of visual outcome is a new finding and lends support to the common clinical practice of repeating photocoagulation if initial treatment does not reduce or stabilize retinal neovascularization. PMID- 2912912 TI - Failure of vitamin E to protect the retina against damage resulting from bright cyclic light exposure. AB - Cumulative light-mediated damage to the retina over a long time period may be involved in the development of age-related retinopathies. Light is thought to produce retinal damage by initiating autoxidative reactions among the molecular components of the retina. Experiments were therefore conducted (1) to confirm that long-term differences in cyclic light intensity affect the rate of age related photoreceptor cell loss from the retina; and (2) to determine whether the antioxidant, vitamin E, is an effective inhibitor of damage to the retina by bright cyclic light. Albino rats were fed a basal diet either supplemented with or deficient in vitamin E. Each dietary group was divided into two light treatment groups which were exposed to 12 hr cyclic light of either 15 lux or 750 lux. After 10 and 17 weeks of treatment, retinal photoreceptor cell densities were determined for animals in each group. Vitamin E deficiency resulted in moderate decreases in photoreceptor cell densities in the dim-light groups after both 10 and 17 weeks. Rats exposed to the bright-light condition suffered a pronounced loss of photoreceptor cells by 10 weeks, and an even greater cell loss by 17 weeks. Vitamin E deficiency did not enhance the effect of bright cyclic light in reducing photoreceptor cell densities. Thus, it appears unlikely that retinal damage by cyclic light occurs via an autoxidative mechanism. PMID- 2912913 TI - Retinal light damage reduces autofluorescent pigment deposition in the retinal pigment epithelium. AB - Lipofuscin in the retinal pigment epithelium (RPE) is thought to be derived from phagocytosed photoreceptor outer segment disc membranes. Based on this hypothesis, one would predict that the rate of lipofuscin deposition in the RPE would be proportional to the density of photoreceptor cells in the retina. In previous studies it was demonstrated that specific loss of photoreceptor cells due to a genetic defect resulted in a substantial decrease in the rate of age related lipofuscin accumulation in the RPE. In order to confirm that this decreased RPE lipofuscin deposition was directly related to reduced photoreceptor cell density, experiments were conducted to determine whether light-induced photoreceptor cell destruction affected RPE lipofuscin content. The effects of retinal light damage on RPE autofluorescent pigment accumulation resulting from both normal aging and vitamin E deficiency were examined. Starting immediately after weaning, albino Fisher 344 rats were fed diets either containing or lacking vitamin E. All animals were maintained on a 12 hr/12 hr light/dark cycle. During the light phases of the cycles, the cage illuminance for one-half the animals in each dietary group was 750 lux, while the remaining rats were exposed to a light level of 15 lux. Illumination was provided by 40 watt cool-white fluorescent lamps. After 17 weeks, rats in both dietary groups that were maintained under the higher light intensity had substantially reduced photoreceptor cell densities relative to animals in the same dietary group maintained under dim light conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2912914 TI - Four cone types characterized by anti-visual pigment antibodies in the pigeon retina. AB - Using three antibodies to visual pigments (monoclonal antibodies COS-1 and OS-2, and a polyclonal anti-opsin serum), four different types of cone cells could be distinguished in the red area (dorsoposterior part with the highest density of cones) of the pigeon retina. Both members of the double cone and the single cone with the red oil droplet were labelled with our monoclonal antibody COS-1 (type I cone). The single cone with the orange oil droplet was positive both with anti opsin and monoclonal antibody OS-2 (type II cone). The single cone exhibiting a yellowish-green oil droplet, fluorescent in ultraviolet light, also reacted with anti-opsin but lacked the antigenic determinant recognized by OS-2 (type III cone). The thin cone with the small colorless oil droplet was negative with both COS-1 and anti-rhodopsin (type IV cone). We propose that the four immunologically distinguishable cone types correspond to cones expressing visual pigments with different (long-, middle-, short-wavelength and ultraviolet) color sensitivities. PMID- 2912915 TI - The formation of autofluorescent granules in cultured human RPE. AB - Although the incomplete degradation of phagocytosed outer segment discs is thought to result in the formation of lipofuscin, there has to date been no proof of this concept. We report for the first time that cultured human retinal pigment epithelial (RPE) cells fed daily doses of isolated rod outer segments for periods of up to 3 months were capable of developing intracellular autofluorescent granules whose morphology and fluorescence characteristics were similar to lipofuscin. These autofluorescent granules were observed as early as 2 weeks following daily challenge with rod outer segments and the number of granules increased with the number of challenge doses until the experiment was terminated after 3 months of daily feeding. We also studied the effects of the antioxidant vitamin E and a drug, Centrophenoxine, which has been purported to slow the formation of lipofuscin formation in vivo. Neither of these additives given either with the challenge or subsequently had any effect on the formation of the intracellular granules. In conclusion, the development of these "lipofuscin-like" inclusions in cultured RPE may provide a model with which to study ageing processes and may provide an understanding of the increased lipofuscin accumulation observed in certain retinal pathologies. PMID- 2912916 TI - Corneal surface ablation by 193 nm excimer laser and wound healing in rabbits. AB - The 193 nm argon fluoride excimer laser was used to ablate a 6 mm diameter area of the central rabbit cornea under various conditions of power, beam configuration and exposure time. High repetition rates or prolonged exposures produced charring and prevented rapid epithelial wound closure. Endothelial vacuolization, reduction in density, and displacement of cell material into Descemet's layer resulted in these experiments. A beam of low and uniform power intensity (40 pulses per second, 100 seconds at 23 mJ/cm2) reduced stromal damage, cellular infiltration, and epithelial irregularities including punctate staining and cell exfoliation. Epithelial rehealing occurred within two days. Basal lamina and hemidesmosomes were reformed by one week. Endothelial damage was not detected. Excimer laser ablation may allow removal of superficial dystrophies or scars, followed by rapid healing from normal corneal reparative processes. PMID- 2912917 TI - Femtosecond optical ranging of corneal incision depth. AB - Excimer laser ablation has been proposed as a technique for keratorefractive surgery. Clinical acceptance of linear-incision laser keratectomy may depend on the availability of a method for accurately and noninvasively monitoring incision depth during the ablation process. We have developed a femto-second optical ranging technique for measurement of corneal incision depth. This technique uses nonlinear optical cross-correlation to determine the time-of-flight of an ultrashort laser pulse between the anterior corneal surface and the bottom of the keratectomy incision. Longitudinal and transverse resolution are estimated to be 5 micron and 10 micron, respectively. PMID- 2912918 TI - Near drowning consensus and controversies in pulmonary and cerebral resuscitation. PMID- 2912919 TI - Thermal dilution measurements of cardiac output. PMID- 2912920 TI - Legislation to legalize active euthanasia. PMID- 2912922 TI - Suggestions for health care providers in critical care units. PMID- 2912921 TI - Stress ulceration in the critically ill. PMID- 2912923 TI - Noninvasive temporary pacing: experience in a community hospital. AB - During a 1-year period 37 patients who underwent treatment with a noninvasive temporary pacemaker were followed to evaluate effectiveness and outcome of therapy. The device was most frequently used in the emergency department and coronary care unit and was applied by a nurse in 51% of cases. Pacing thresholds ranged from 20 to 110 mA (mean 43 mA) with 91% obtaining capture. Pacing was continuous in 11 patients for 5 to 180 minutes (mean 32 minutes) and intermittent in 16 patients for up to 72 hours. Pacing did not take place in 10 patients because of failure to capture or because a satisfactory intrinsic rate was maintained. After external pacing, six patients received permanent pacemakers, 14 required temporary transvenous pacemakers, 10 required no further pacing, and seven (19%) died. Few problems were encountered, although eight of the 20 responsive patients had severe discomfort related to pacing, with two of these requiring discontinuation of pacing. The number of temporary transvenous pacemaker insertions in the coronary care unit decreased 32% over a 6-month period after introduction of the noninvasive temporary pacemaker. We conclude that the noninvasive temporary pacemaker is safe and effective although discomfort may limit its use in some patients. PMID- 2912924 TI - Smoking practices of critical care nurses. AB - This study examined smoking practices of 499 critical care nurses, their knowledge about the health effects of smoking, and their perceptions regarding responsibility for promoting and supporting antismoking efforts. Approximately 20% of the critical care nurses surveyed were current smokers. Overall, respondents were knowledgeable about the serious consequences of smoking. Although they tended to view themselves as responsible for taking an active role in smoking cessation efforts, they had reservations about their ability to achieve successful outcomes. This information provides a data base for designing smoking cessation strategies for critical care nurses and educational interventions aimed at increasing skills in helping patients cope with the abrupt withdrawal from nicotine imposed by an episode of acute illness. PMID- 2912925 TI - Effects of conversation on intracranial pressure in comatose patients. AB - In this time series design study we investigated the effects of conversation on intracranial pressure (ICP). Two conversation types were used, and continuous measurements of ICP were recorded. Type 1 conversation was an emotionally referenced conversation that reflected an actual nursing report on the patient's current condition. Type 2 conversation was a predetermined dialogue unrelated to the patient. Two hypotheses were tested to determine the existence of differences between the ICP measurements at baseline and the ICP measurements during any conversation, and differences between the ICP measurements recorded during type 1 conversation and during type 2 conversation. Eight subjects served as their own control. T tests were performed between the mean scores of the minimum, maximum, and average ICP measurements before, during, and after both conversations. The hypotheses were not supported by the findings. There was, however, a statistically significant decrease in ICP when minimum ICP measurements before type 2 conversations were compared with measurements recorded during type 2 conversation. The data also demonstrated a wide variation of individual patient responses. The results of the current study suggest that the direction of influence from conversation on the ICP is individual and may be influenced greatly by the patient's level of consciousness. PMID- 2912926 TI - Critical care nursing: future challenges. PMID- 2912927 TI - Effectiveness of oxygen concentrations of less than 100% before and after endotracheal suction in patients with chronic obstructive pulmonary disease. AB - This within-subject study compared the effects of hyperinflations with 20% above maintenance oxygen (O2) level and 100% O2 hyperinflations before and after endotracheal suction in 11 acutely ill patients with chronic obstructive pulmonary disease. Four hyperinflations were delivered at 1.5 times the calculated tidal volume (10 ml/kg) with 100% O2 or 20% above maintenance O2 level via resuscitator bag, followed by 10 seconds of continuous endotracheal suctioning. This sequence was repeated three times. No statistically significant differences (p less than 0.05) were found between the two protocols for arterial oxygen saturation, blood pressure, or heart rate (analysis of variance for repeated measures). There was no change in heart rhythm for any of the subjects. The results of this study suggest that hyperinflation with 20% above maintenance O2 level can be used for oxygenation in patients with chronic obstructive pulmonary disease before and after endotracheal suctioning. Replication is needed before clinical implementation. PMID- 2912928 TI - Cardiac rhythm responses. 1. An important phenomenon for nursing practice, science, and research. AB - The human responses to actual or potential health problems that are of interest to nursing encompass physiologic, psychologic, and sociocultural responses. Measurement of cardiac rhythm responses provides a unique opportunity to look at the complex interplay of physiologic, emotional, and environmental factors at a particular time. A model depicting the relationships between cardiac rhythm responses and the central nursing domain concepts of individual, environment, health, transitions, and nursing therapeutics is presented. Measurement of cardiac rhythm responses provides an objective, quantifiable, noninvasive, inexpensive, readily accessible, reliable, and valid tool for measuring human responses. Study of the phenomenon holds promise for nursing practice, science, and research fostering links among the three. Study of cardiac rhythm responses will have direct applicability to practice with the potential for narrowing the research-practice gap. Moreover, study of the phenomenon will contribute to nursing knowledge and foster advancement of nursing science by the development of theory. PMID- 2912929 TI - Nephrotic syndrome: a nursing care plan based on current pathophysiologic concepts. AB - The classic conception of the pathophysiology of the nephrotic syndrome (NS) is now being seriously questioned, on the basis of current research findings. New conceptions of the syndrome, with its proteinuria, hypoalbuminemia, and edema, are providing explanations for the discrepancies between the original theory and clinical data from individual patients, particularly related to edema formation. Many of the edema-preventing mechanisms are normal in patients with NS, but may fail when plasma osmotic pressure falls significantly. Plasma volumes, blood volumes, and blood pressures of patients with NS have been found to be generally normal or slightly increased, in contrast to the classic "hypovolemia" theory. Activation of the renin-angiotension-aldosterone system is variable and cannot fully explain the sodium and water retention. The decreased renal filtration rates and abnormal sodium retention/excretion rates are now best explained by an intrarenal defect, on the basis of multiple research approaches. These research conceptions of the pathophysiology of NS are significant for nurses because they can be used in patient assessment, interpretation of patient data, monitoring during treatment, collaboration about the plan of care, development of nursing care plans, and patient teaching. Several nursing diagnoses may be appropriate for patients with NS: alteration in fluid volume: excess; potential for infection; alteration in nutrition: less than body requirements, potential alteration in comfort; knowledge deficit; and potential disturbance in self concept: body image. PMID- 2912930 TI - Social advocacy. PMID- 2912931 TI - Quantitative morphology of late renal radiation injury. AB - Late radiation injury manifests itself in all morphologic compartments of the kidney, but loss of cell mass is most significant in the proximal convoluted tubules. Development of an end stage or nonfunctional kidney requires 12 or more months after single fraction X ray exposures of about 12 Gy (2, 5, 13) and is associated with marked morphologic alterations of renal tubules. Radiation induced changes were studied at 6 months after irradiation, a time interval when histological alterations appear minor, but in previous studies were shown to correlate with the later end stage alterations (5, 8, 9). Renal alterations were graded objectively based on renal weight, variation in size of tubule cell nuclei, and glomerular nuclear volume fraction. Irradiation was associated with loss of renal weight, increased variability of tubule nuclear size, and previously unappreciated changes in glomerular nuclear volume fraction. A classification index derived from a weighted combination of renal weight ratio and tubule cell nuclear variability correlates with radiation dose and with previously established subjective histologic grading of renal damage, and allows objective comparisons of various fractionation schedules. PMID- 2912932 TI - The use of CT densitometry in the assessment of radiation-induced damage to the rat lung: a comparison with other endpoints. AB - Changes in rat lung following irradiation have been assessed on the basis of survival, histopathology, function (breathing rate assay), and density changes measured by computed tomography (CT) scanning. CT densitometry is a non-invasive procedure which may be used without modification to assess lung damage in experimental animals and in man. An increase in the breathing rate is seen following irradiation of the thorax, the time of onset and severity of which are dose dependent and correlate with histopathological changes occurring at the same time. Lung density changes occurring after irradiation are more complex. For the lowest dose used (10.75 Gy) no density increase was observed and in fact density decreased with time after irradiation to a slightly greater extent than in non irradiated controls. A post-irradiation increase in lung density was seen for rats given 13.0 Gy, but values fluctuated with maxima at 50 and 225 days after irradiation. Higher radiation doses (14.5, 16.0 Gy) were followed by a transient decrease in density before a dose-related density increase was observed. Density averaged over the whole lung proved to be a sub-optimal index of radiation induced lung damage because of the focal nature of radiation-induced lung lesions and because of the apparently anomalous changes in post-irradiation damage which are observed. Further studies are being made to determine if regional density values will provide a more sensitive index. PMID- 2912933 TI - Response of the canine lung to fractionated irradiation: pathologic changes and isoeffect curves. AB - Canine lungs were irradiated with a range of total doses given in 2, 3, or 4 Gy per fraction. Sequential histopathologic evaluations were done at 1, 3, 6, and 12 months. Pathologic changes in canine lungs were found to be similar to those found in other species demonstrating a clinically latent period, a pneumonitis phase, and late fibrosis and vascular damage. The relative impact of endothelial cell and pneumocyte injury on either early or late radiation injury of the lung is difficult to resolve. Therefore, it is not possible to define a target cell for lung injury at this time. The alpha/beta ratios determined in this study indicate that the target cell or cells associated with lung consolidation are slowly proliferating and represent late responding tissues. Lungs were evaluated histomorphometrically for alveolar air space and radiographically for alveolar consolidation at 6 months after irradiation. Alpha/beta ratios of 3 Gy and 4 Gy were calculated respectively. Both assays demonstrated an increasing effect on lung damage with increasing fraction size from 2 to 4 Gy. Application of the LQ model and use of alpha/beta ratios for calculation of dose adjustments remains theoretical. Clinical data are insufficient to define specific alpha/beta ratios for the various normal tissues at risk in radiation therapy. The data are sufficient to demonstrate the sparing effects of decreasing size of dose per fraction for late responding tissue. Results of this study suggest caution against the use of large doses per fraction for radiation therapy fields which include large lung volumes. PMID- 2912934 TI - Response of human tumor cell lines in vitro to fractionated irradiation. AB - The surviving fraction of human tumor cell lines after 2 Gy (SF2) varies between 0.1 and 0.8. It has been postulated that differences in inherent radiosensitivity of tumor cells are a major determinant of radiation response in vivo. Assays of inherent radiosensitivity based on acute survival are being developed as predictors of tumor response which often assume that the same inherent radiosensitivity persists throughout a fractionated treatment. We have investigated the response of 2 human tumor cell lines (A549 and MCF7) with different inherent radiosensitivities to in vitro fractionated irradiation. A549 cells had an SF2 of 0.62 and a mean inactivation dose (D) of 3.07 Gy whereas MCF7 cells had an SF2 of 0.30 and a D of 1.52 Gy. Split dose repair capacity (at equal survival levels) was less for A549 than for MCF7 cells and recovery kinetics for both cell lines were substantially longer than those of rodent cell lines. Survival after 5 fractions of 2 Gy given 12 hr apart at 37 degrees C was near to that predicted from the acute survival curve, assuming complete repair and no proliferation. Acute survival of A549 cells which survived 5 fractions of 2 Gy given 12 hr apart was similar to the acute survival of unirradiated cells. When A549 cells were incubated at 22 degrees C between 5 fractions of 2 Gy given 12 hr apart, proliferation and split dose repair were substantially inhibited. These studies support the proposals to use in vitro inherent radiosensitivity assays for the prediction of in vivo response of tumors to fractionated treatment. PMID- 2912935 TI - Tumor bed effect-induced reduction of tumor radiocurability through the increase in hypoxic cell fraction. AB - Two murine tumors, designated FSA and SA-NH, that exhibit strong tumor bed effect (TBE), were found to be less radiocurable if they grew in the preirradiated s.c. tissue. Tumors were transplanted into the right thighs irradiated with 30 Gy one day earlier, and were irradiated when they grew to 6 mm. The TBE-caused reduction in tumor radiocurability was manifested by the increase in TCD50 values. Tumor irradiation under hypoxic conditions increased TCD50 values less, and the hypoxic cell radiosensitizer misonidazole reduced TCD50 values more, when tumors grew in preirradiated than when they grew in unirradiated legs. This implies that TBE induced increase in TCD50 was due to increase in hypoxic fraction of tumor cells. For 6 mm SA-NH tumor the estimated increase in hypoxic cell fraction was from the control value of 3% to 12%. Thus, TBE causes the reduction in tumor radiocurability through the increase in hypoxic fraction of tumor cells. PMID- 2912936 TI - 3H-misonidazole labeling and viability of hypoxic cells in the sandwich system, an in vitro tumor analogue. AB - 3H-misonidazole was used as a marker of hypoxic cells in an in vitro tumor analogue, the sandwich system. MISO binding was assessed in situ, using autoradiography. Binding profiles indicate that there are regions of radiobiological hypoxia surrounding the necrotic center in sandwiches of the V79 cell line and in sandwiches of the 9L cell line. Grains per cell were counted and detailed statistics on the variation of intrinsic binding among cells in the same microenvironment are presented. There is a systematic decrease in the standard deviation of grains per cell as one examines populations of cells further and further from the nutrient and oxygen source. Kinetic studies show that the growth fraction of the cell population also decreases with distance from the nutrient source. These findings taken together suggest that MISO binding is proportional to cell size and cells in the inner noncycling portion of the sandwich are more nearly uniform in size. Sandwich cells which exhibit heavy MISO binding, and are presumably radiobiologically hypoxic, were shown to be still viable if restored to good nutrient and oxygen conditions. PMID- 2912937 TI - Phosphorus-31 magnetic resonance spectroscopy and blood perfusion of the RIF-1 tumor following X-irradiation. AB - Phosphorus-31 magnetic resonance spectra were obtained from the RIF-1 tumor in C3H mice before and up to 2 days after various doses of X rays. Parallel studies were performed to measure relative changes in tumor blood perfusion using [14C]iodo-antipyrine and changes in % tumor necrosis using Chalkley's method. Tumor ratios of phosphocreatine to inorganic phosphate (PCr/Pi) and nucleotide triphosphates to inorganic phosphate (NTP/Pi) as well as pH as measured by 31P MRS increased significantly at most time points after irradiation with doses of 5, 10, and 20 Gy. Tumor blood perfusion was found to significantly improve after a dose of 20 Gy but not after a dose of 2 Gy. Percent tumor necrosis increased to about 3 times its control level at 1 day after a dose of 20 Gy and then declined to about twice its control value at 2 days. The magnitude of the changes in the 31P-MRS parameters makes it unlikely that any of them are entirely due to radiation-induced changes in the radiobiologically hypoxic fraction of these tumors. Changes in the necrotic fraction did not appear to influence the tumor spectra. However, the observed improvement in tumor blood perfusion may have resulted in an increase in oxidative phosphorylation of the whole tumor population as well as a clearance of inorganic phosphate and acid metabolites, so that 31P-MRS changes may indirectly reflect changes in tumor blood perfusion. PMID- 2912938 TI - A comparison of the roles of surgery and radiation therapy in the management of craniopharyngiomas. AB - Fifty-two patients with craniopharyngioma were seen between January 1961 and July 1986. Of these, 40 were treated with surgery alone, 8 with surgery and postoperative radiotherapy, and 3 with radiotherapy alone. One patient received no treatment. For the group treated with surgery alone, 33% (13/40) had local tumor control, 42.5% (17/40) developed major complications, and 71% (25/35) survived 5 years. With surgery and postoperative radiotherapy, 100% (8/8) had local tumor control, 25% (2/8) developed major complications, and 100% (7/7) survived 5 years. Two of the three patients treated with radiotherapy alone had local tumor control and the third was salvaged with surgery. The "complete resection" rate for 32 patients treated with radical surgery was 63% (20/32). Tumor control was achieved in 50% (10/20) of the patients treated with "complete resection" without radiotherapy, in 15% (3/20) of the patients treated with "incomplete resection" without radiotherapy, and in 100% (8/8) of the patients treated with "incomplete resection" and postoperative radiotherapy. In this series, doses of 5000-5500 cGy were as effective in achieving control as 5500 6000 or 6000-7000 cGy. PMID- 2912939 TI - Auger electron contribution to bromodeoxyuridine cellular radiosensitization. AB - Halogenated thymidine analogs become incorporated into the DNA of proliferating cells during S-phase and may be used clinically to radiosensitize tumors that are otherwise poorly responsive to radiation. Although radiosensitization has been studied for years, mechanisms of radiosensitization are poorly understood. One possible mechanism involves the release of short range, high-LET, Auger electrons following photoelectric absorption of an X ray by the K-shell of the incorporated halogen. Such absorption occurs only with X ray energies slightly greater than the K-shell binding energy. We report the results of an experiment designed to measure this effect, in which cultured monolayers of Chinese hamster V79 cells, with 32% replacement of thymidine by bromodeoxyuridine (BUdR), were exposed to monoenergetic X rays just below (13.450 KeV) or above (13.490 KeV) the K-edge (13.475 KeV) of bromine. Enhancement ratios calculated in five different ways were slightly increased (3-12%) above the K-edge compared to below. However, only a calculation using a linear-quadratic fit to the data and a surviving fraction of 0.01 demonstrated a statistically significant increased enhancement ratio (12%) above the K-edge. We conclude that Auger electrons produced following photoelectric absorption of X rays by the K-shell of bromine contribute minimally to observed BUdR cellular radiosensitization. PMID- 2912940 TI - Interaction between the microtubule inhibitor tubulozole and gamma-irradiation in murine tumors in vivo. AB - The combined effect of the microtubule inhibitor tubulozole and gamma-irradiation has been investigated in vivo in subcutaneous MO4 fibrosarcomas and Lewis Lung carcinomas. A marked interactive effect on tumor growth was observed when 160 mg/kg tubulozole was orally administered before the tumors were treated with 10 Gy radiation. Dose dependency and optimal effect were obtained on tumor growth of MO4 tumor bearing animals when the drug treatment was given 6 hr prior to the irradiation. The optimal pretreatment time coincided with the time at which a peak mitotic index in the tumor tissue was observed. An enhancing effect is also noticed at other doses of radiation in MO4 tumors pretreated 6 hr before with 160 mg/kg tubulozole. The interactive effect is maintained in a clinically relevant dose fractionation schedule whereby 8 fractions of 2 Gy each were pretreated 6 hr before with 80 mg/kg tubulozole. Tubulozole-T, the stereo-isomer of tubulozole, neither exhibits any antimicrotubular action nor exerts an antitumoral effect on its own or in combination with gamma-irradiation. The possible mechanisms of interaction between tubulozole and gamma-irradiation in tumor tissue are discussed. PMID- 2912941 TI - Hyperthermic "dose" dependent changes in intralesional pH. AB - Following hyperthermia a dramatic drop in intra-lesional pH has occurred in a variety of experimental tumor systems. To date, no direct observations have been made that document the time course of such changes or the recovery from such changes over prolonged periods of time. These experiments were designed to measure intralesional pH as a function of time following "doses" of hyperthermia related to specific biological end points. All studies were conducted in the C3H mammary carcinoma tumor model system. Intralesional temperature was continuously monitored throughout treatment and post treatment pH was measured with microelectrodes at several specific time points ranging from 4 hrs to 7 days. The pretreatment control value of mean pH was 6.73. At the TCD90 "dose" level the mean value of pH dropped to a level of 6.22 +/- .095 while following the TCD10 "dose" the value obtained was 6.55 +/- .148. Recovery of the pH to higher values followed similar time courses returning to maximum values approximately 3 days post treatment. The recovery, plateau levels of pH were however, separated by approximately .3 pH units with the higher "dose" curve always at lower values than that achieved following the lower "dose". PMID- 2912942 TI - The effect of hyperthermia on the uptake and cytotoxicity of melphalan in Chinese hamster ovary cells. AB - The effect of temperature on the cytotoxicity of melphalan in CHO cells was studied in an in vitro clonogenic assay. The cytotoxicity of melphalan was significantly increased at elevated temperatures with a 4 fold increase in cytotoxicity at 42 degrees C compared to 37 degrees C. The effect of temperature on membrane permeability to melphalan was studied to determine whether the increase in cytotoxicity was due to increased intracellular drug levels. Melphalan influx and efflux rates both increase with increasing temperature. There is, however, a small net increase in steady state intracellular drug levels with increasing temperature with a 20% increase in intracellular drug levels at 42 degrees C compared to 37 degrees C. The increase in drug uptake observed in insufficient to explain the much greater increase in cytotoxicity with increasing temperature. PMID- 2912943 TI - Response of mediastinal Hodgkin's disease to radiotherapy: rate of tumor regression not predictive of outcome. AB - The record of 18 patients with Stage II Hodgkin's disease and large mediastinal masses, who received radiation therapy as sole treatment for their disease, were reviewed. The ratio of each patient's maximum tumor diameter to his maximum transthoracic diameter was measured from radiographs taken prior to treatment, and at two intervals approximating 1/3 and 2/3 the total radiation dose. The slopes of the resulting graphed data points were correlated with patient outcomes. No correlation could be drawn between prompt or slow tumor regression and freedom from tumor recurrence. It is concluded that the rate of tumor mass regression in Hodgkin's disease is not predictive of the ultimate success or failure of radiation therapy, and should not be used as a criterion by which to judge the need for additional systemic chemotherapy. PMID- 2912944 TI - Treatment planning for permanent and temporary percutaneous implants with custom made templates. AB - Nine patients who were presented at MSKCC with primary or recurrent pelvic or head and neck tumors and for whom surgery or further external radiation were excluded, were treated with percutaneous permanent or temporary implants, with individual pre-treatment planning and custom made templates. The tumor dose distributions achieved were as good as for implants performed at the time of surgical exploration. No serious complications have been encountered. PMID- 2912945 TI - A study of splenic irradiation in chronic lymphocytic leukemia. AB - A retrospective study was performed to assess the effect of splenic irradiation (SI) on splenomegaly, splenic pain, anemia, and thrombocytopenia in patients with chronic lymphocytic leukemia. Twenty-two patients received 32 courses of SI. Of 31 courses of SI given for splenomegaly there were 19 responders (61%). Ten courses of SI were given for splenic pain resulting in partial relief of pain in 4 courses and complete relief in 4 courses. Only 4 of 16 courses given for anemia resulted in elevations of hemaglobin of 2 g/dL or more. Of the 14 courses of SI given for thrombocytopenia there were only 2 responses with platelet counts decreasing further in another 9 courses. The median duration of response was 14 months (range: 3-116 months). There was no dose-response relationship detected for SI in CLL. Treatment related toxicity was hematologic and secondary to leucopenia and thrombocytopenia. We recommend the use of small fraction sizes of 25 cGy to 50 cGy and close monitoring of hematological parameters. Splenic irradiation effectively palliates splenomegaly and reduces spleen size in CLL. It was of limited value in correcting anemia and thrombocytopenia in this patient population. PMID- 2912946 TI - The value of treatment planning using CT and an immobilizing shell in radiotherapy for paranasal sinus carcinomas. AB - This article describes a method which uses CT scans and immobilizing shells radiation treatment planning (CT-assisted planning) for paranasal sinus carcinomas and the value of this method on the treatment outcome. Results of the treatment for 82 patients who had CT-assisted planning were compared with that of 88 patients who had no such treatment planning. It has been concluded that the combined use of CT and the shell in treatment planning permitted a 3-dimensional localization of both the tumor and critical normal structures with great accuracy, leading to an improved long-term survival and a reduced complication rate. The multivariate regression analysis for predicting significant prognostic factors also confirmed the valuable role of CT in terms of survival and primary tumor control. The actuarial 5-year survival rate was 51% in all patients, whereas, by using CT-assisted planning, it was improved to 61%. The improved survival was observed among the patients with tumors of the suprastructures where tumors were located adjacent to the critical organs (brain and eye). Major complications attributable to radiation have included instances of brain and ocular damage. CT-assisted planning, however, has been proven effective in avoiding brain necrosis and preserving eye sight. PMID- 2912947 TI - Postoperative irradiation for squamous cell carcinoma of the head and neck: an analysis of treatment results and complications. AB - One hundred thirty-four patients with advanced head and neck cancer were treated with radical surgery and postoperative radiation therapy between October 1964 and October 1984. All patients had greater than or equal to 2 years and 84% had greater than or equal to 5 years of follow-up. All patients included in the study were scheduled to receive continuous-course irradiation following a major cancer operation for previously untreated squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx and began radiation treatment less than or equal to 3 months after the surgical procedure. Ninety-six percent had AJCC pathologic Stage III or IV cancer, and all were without evidence of gross disease at the start of irradiation. The majority of recurrences above the clavicles occurred in the primary field (84%) as opposed to the posterior strip (8%) or low neck (8%). Based on multivariate analysis and tabular comparisons, 4 factors were found to be significantly important for predicting disease control above the clavicles: (a) Surgical margin (5-year actuarial control with invasive cancer at the margin, 53%, versus 81% with negative margins, p = .009). Patients with close margins or in situ cancer at the margins had the same rate of control as those with negative margins. (b) Primary site (oral cavity, 64%, versus other sites, 83%; p = .029). (c) Neck Stage (N0-1 versus N2-3). (d) Number of indications for irradiation--for example, bone invasion, multiple positive nodes, perineural invasion (1-3 indications, 85%, versus greater than or equal to 4, 62%; p = .06). The rate of disease control above the clavicles did not correlate well with AJCC pathologic stage: Stage I-II, 67%; Stage III, 81%; Stage IVA (T1-3, N2-3A), 68%; Stage IVB (T4 and/or N3B), 80%. The interval between surgery and the start of irradiation (range 1-10 weeks) also was not prognostically important, even with stratification by tumor dose, surgical margin, and number of indications for irradiation. At 5 years, the actuarial survival rate was 33% for the entire group; for patients with invasive cancer at the margin, the survival rate was approximately half that of those whose margins were free of invasive cancer (17% versus 37%). Based on multivariate analysis, 2 factors were found to significantly increase the probability of death due to cancer: (a) neck Stage (N0 1 versus N2-3); (b) extension of tumor from the primary site into the skin or soft tissues of the neck.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2912948 TI - A new technique for endocavitary irradiation of the esophagus. AB - Recently, high-dose rate intracavitary irradiation has been used as a boost therapy or a palliative therapy in the treatment of the esophageal carcinoma. The new intraesophageal device is based on a modified Sengstaken-Blackemore tube. On the surface of the esophageal balloon of the S-B tube Cyponil tubes are fixed as iridium containers. The device is placed at the level of the neoplastic lesion. Treatment tolerance is good. PMID- 2912949 TI - Three-dimensional display techniques in radiation therapy treatment planning. AB - Good radiation treatment planning requires that the target volume be treated with a high and uniform dose of radiation while irradiating normal tissue as little as possible. Even if the merits of a given treatment plan are judged only on the appearance of isodose lines in one or a few planes it can sometimes be difficult for the experienced radiation oncologist to select the best of several alternative plans. If consideration is given to the entire spatial distribution of dose, however, the problem becomes far more difficult because of the enormous amount of data that must be evaluated. We believe that the lack of suitable methods to display these data has greatly contributed to the slow incorporation of 3D considerations into routine radiation treatment planning. In the past few years there have been great advances in both the theory of how to produce effective 3D displays and in the display hardware itself. In this paper we survey some of the methods used at the University of North Carolina, and show specific examples of how these displays can be used in radiation therapy treatment planning. PMID- 2912951 TI - Methods: endocavitary irradiation. PMID- 2912950 TI - Semi-automated radiotherapy treatment planning with a mathematical model to satisfy treatment goals. AB - Iterative algorithms can provide a feasible solution, if any exists, to specified treatment goals. Our model subdivides both the patient's cross section into a fine grid of points and the radiation beam into a set of "pencil" rays. The anatomy, treatment machine parameters, dose limits and homogeneity, are all defined. This process of subdivision leads to a large system of linear inequalities with a solution that provides a radiation intensity distribution that will deliver a prescribed dose distribution. The clinical results from two different algorithms will be presented and contrasted. Once the anatomy, treatment, and machine parameters have been entered, the computerized algorithms yield an answer in several minutes. The Cimmino algorithm also allows "weights" or priority assignments of the treatment goals. The resulting solution is biased towards fulfilling the specified doses for the anatomic regions which were given greater weight. It is desirable to have a systematic search of possible treatment alternatives in complex clinical situations, including 3-dimensional radiation therapy treatment planning (RTTP). Our method has been applied to 2-D RTTP, but is equally applicable to 3-D RTTP with minor modifications. PMID- 2912952 TI - Long SSD endocavitary rectal irradiation technique. PMID- 2912953 TI - The role of cranial irradiation in low risk ALL. PMID- 2912954 TI - Molecular mechanisms of oxygen and "electron-affinic" radiosensitizers. PMID- 2912955 TI - Prognosis following local or regional recurrence after conservative surgery and radiotherapy for early stage breast carcinoma. AB - Factors which influence patient prognosis following a breast recurrence or regional nodal recurrence after initial treatment of early-stage invasive breast carcinoma with conservative surgery and radiotherapy are not well known. Ninety patients treated at the Joint Center for Radiation Therapy treated from 1968-1981 had a recurrence in the treated breast before (84) or simultaneous with (6) distant metastases. Sixty-five patients had salvage mastectomy (median subsequent follow-up in patients without further disease, 32 months; range, 1-123 months). The five-year rate of further recurrence in this group was 37%. The most important variable associated with subsequent outcome was the histology of the recurrent tumor. There were no further recurrences among 10 patients with purely non-invasive cancer or 10 patients with predominantly non-invasive disease and only focal areas of invasion. In contrast, 17/45 patients (38%) with predominantly infiltrating tumors suffered further local-regional recurrences (6) or distant metastases (11) following mastectomy (5-year actuarial rate, 55%) (p less than 0.05). Ten patients developed regional nodal failures without evidence of simultaneous breast recurrence (1 internal mammary, 3 supraclavicular, 1 both supraclavicular and axillary, and 5 axillary). Only 3 of these 10 (all with axillary node failures) did not have simultaneous distant metastases; they remain alive without evidence of further distant or local-regional recurrence following salvage treatment 1, 59, and 87 months after recurrence. We conclude that the great majority of the patients (88% in this series) who have a breast recurrence following initial conservative surgery and radiation therapy for early stage breast carcinoma will have disease limited to the breast clinically and tumors amenable to salvage mastectomy. Salvage mastectomy appears to be effective treatment for patients with an isolated breast recurrence, especially if the recurrence is predominantly or wholly non-invasive. PMID- 2912956 TI - Prognostic value of hemoglobin concentrations and blood transfusions in advanced carcinoma of the cervix treated by radiation therapy: results of a retrospective study of 386 patients. AB - A retrospective study was carried out on 386 patients with advanced cervical carcinomas treated with radiation therapy between 1973 and 1983. The influence of hemoglobin concentrations and blood transfusions before and/or during treatment on the occurrence of distant and/or local regional failures were examined in a univariate and multivariate analyses. In the multivariate analysis hemoglobin concentrations were prognostic only during treatment and patients with at least one value below the threshold of 10 gm% had a significantly higher risk of local regional failure than the patients with all their values above the threshold. Moreover 70% of these high risk patients had less than half of their values below the threshold. It is possible that blood transfusions might be beneficial when given before treatment. However, although it was not significant, blood transfusions given during treatment tended to be an adverse prognostic factor suggesting that blood transfusions might not have completely offset acute anemia prior to transfusion. Our study suggests that anemia during treatment, even of short duration might be detrimental to patients. PMID- 2912957 TI - Solitary plasmacytoma of bone: Mayo Clinic experience. AB - A review of 46 cases of solitary plasmacytoma of bone was undertaken in an attempt to better define the clinical features and prognostic indicators associated with this disease. Criteria for inclusion in the study included the following: (a) solitary lytic bone lesion on skeletal survey; (b) histologic confirmation of the lesion; and (c) bone marrow plasmacytosis of less than 10 percent. Patients with extramedullary plasmacytomas and osteosclerotic lesions were excluded. All patients were evaluated with serum and urine protein studies at the time of diagnosis. The median follow-up was 90 months with a minimum of 30 months. Fifty-four percent of the lesions involved the vertebral column. The thoracic spine was the single most commonly involved site (13/46 patients). The initial lesion was treated with radiotherapy in all but three patients in whom complete surgical resection was achieved. Total doses ranged from less than 20 Gy to 70 Gy with a median of 39.75 Gy. Overall, 54% developed multiple myeloma, 2% failed with new bone lesions without multiple myeloma, and 11% developed local recurrences. No patient receiving 45 Gy or more to the solitary lesion had a local failure. While the median time to progression was 18 months, 23% of the failures occurred after 60 months. The five local failures occurred at 7, 12, 18, 40, and 114 months. The overall survival was 74% at 5 years and 45% at 10 years. The 5- and 10-year disease-free survivals, however, were 43 and 25%, respectively. Evidence of abnormal serum and/or urine protein was found in 25 of 46 patients. Neither survival nor disease-free survival was significantly influenced by the presence of abnormal proteins even if they persisted after irradiation. PMID- 2912958 TI - Results of a prospective study evaluating the effects of mantle irradiation on pulmonary function. AB - Thirty patients with Stages I-III Hodgkin's disease receiving mantle irradiation were prospectively evaluated prior to therapy with spirometry, lung volumes, and tests of diffusing capacity (DLCO). Follow-up examinations were performed at 3, 6, and 12 months and then yearly. Sixteen patients had Hodgkin's disease involving the mediastinum at presentation, 10 were smokers, and 16 received either preirradiation or postirradiation chemotherapy. Mantle doses ranged between 2300 cGy and 4000 cGy (mode of 3750 cGy) given at 150 cGy to 170 cGy tumor dose per day with split-course technique. Pulmonary function test results were translated to percent change from predicted values obtained from normal standards for each age, sex, race, and height. These percent changes were then analyzed as a linear function of time. Twenty patients have been tested greater than or equal to 4 years after treatment with a median time from treatment to last pulmonary function test of 8 years. Changes over time in spirometry included an early, mild decrease in both forced vital capacity (FVC) and forced expiratory volume at 1 second (FEV1), which returned to baseline by 2 years and then gradually decreased to a 10-15% deficit as compared with predicted values at 6-10 years. Additionally, there was a very slight decrease in FEV1/FVC beginning at 1 year and gradually increasing to an 8% deficit at 6-10 years. Changes over time in lung volumes included a mild nadir of total lung capacity (TLC) and functional residual capacity (FRC) at 6 months to a year, which returned to baseline at 2-4 years and then gradually dropped to a 5-10% deficit at 6-10 years. Mean DLCO for the study group was 20% below predicted values prior to treatment and dropped to a low of 30% below predicted at 6 months following treatment, then gradually returned to baseline by 4 years and showed continued improvement to an overall deficit of approximately 10% at 6-10 years. With the exception of FEV1/FVC, the changes noted in spirometry and lung volumes were of insufficient degree to be classified as abnormal. The decrease in FEV1/FVC is indicative of a significant and progressive obstructive ventilatory defect. The effects on pulmonary function tests of smoking, the presence of mediastinal involvement by Hodgkin's disease, and exposure to chemotherapy were assessed by statistical analysis. No subsets of patients demonstrated consistent evidence of a restrictive ventilatory defect expected after irradiation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2912959 TI - Carcinoma of the cervix: analysis of bladder and rectal radiation dose and complications. AB - From April 1969 through December 1980, 527 patients with epidermoid carcinoma of the cervix received radical radiation therapy at North Carolina Memorial Hospital (NCMH). The treatment was designed to deliver a combined dose (external beam plus intracavitary) of 7000-8000 cGy to Point A and 5000-6500 cGy to the pelvic lymph nodes depending upon the stage of the disease. The maximum dose to the bladder and to the rectum were calculated from the orthogonal intracavitary placement films with contrast material in these organs. Thirty-three cases of cystitis and fifty-eight cases of proctitis were recorded. The mean bladder dose for the group of patients with cystitis was higher, 6661 +/- 1309 cGy, than that for the patients without cystitis, 6298 +/- 1305 cGy, p = .19. The risk of cystitis increased as a function of bladder dose ranging from 3% for patients receiving less than or equal to 5000 cGy to the bladder to 12% for patients receiving greater than or equal to 8001 cGy to the bladder. A similar correlation was also found for rectal dose and proctitis. The mean rectal dose for the group of patients with proctitis was higher, 6907 +/- 981 cGy, than that for the patients without proctitis, 6381 +/- 1290 cGy, p = .003. The risk of proctitis increased as a function of rectal dose ranging from 2% for patients receiving less than or equal to 5000 cGy to the rectum to 18% for patients receiving greater than or equal to 8001 cGy to the rectum. A study of the severity of the cystitis as a function of bladder dose revealed a relationship between bladder dose and the severity of the complication (Grade I cystitis = 6600 +/- 1318 cGy vs Grade III cystitis = 6856 +/- 853 cGy). A dose-response relationship was found between the rectal dose and the severity of the complication (Grade I proctitis = 6810 +/- 906 cGy vs Grade III proctitis = 6997 +/- 1137 cGy). This relationship was statistically significant, p = .003. While there was no difference in the frequency of cystitis as a function of dose to the whole pelvis, the risk of proctitis did increase with increasing doses of external beam to the whole pelvis. It ranged from 3% for patients who received 2000 cGy or less to the whole pelvis to 14% for patients who received greater than 4000 cGy to the whole pelvis, p = .02. PMID- 2912960 TI - Studies on the mechanism of the iodination of tyrosine by lactoperoxidase. AB - Studies with lactoperoxidase showed that a highly reactive intermediate is produced (on the enzyme) from I- and H2O2 which then diffuses from the enzyme and very rapidly and indiscriminately iodinates any Tyr or peptides containing Tyr which are in the same solution. The evidence supporting these conclusions follows. 1) The rate followed the Michaelis-Menten pattern with I- and H2O2 while the concentration of Tyr peptides had no measurable effect on the rate; 2) the rates of reaction were independent of the type of peptide in which Tyr was located; 3) the amount of iodination which had occurred after the reaction had gone to completion and the amounts of monoiodination and diiodination after completion of the reaction were independent of the peptide type, the pH, the solvent polarity, or the ionic strength; 4) competition for reaction by two very different Tyr peptides depended only on their initial concentrations; and 5) iodination of a large protein occurred through a dialysis membrane. Free Tyr was iodinated at the same rate as Tyr peptides by lactoperoxidase, but monoiodotyrosine and m-fluorotyrosine were iodinated at one-half that rate. The results also showed that one can choose ratios of [peptide] to [H2O2] such that monoiodination is maximized relative to diiodination. It was also found that the iodination capacity of a mixture of I- and H2O2 with lactoperoxidase (when Tyr was absent) was only slowly dissipated. Finally, the results showed that lactoperoxidase can be used to brominate and chlorinate Tyr peptides at a slow rate. PMID- 2912961 TI - Identification of a Mr = 17,000 protein as the plastoquinone-binding protein in the cytochrome b6-f complex from spinach chloroplasts. AB - An azidoquinone derivative, 3-azido-2-methyl-5-methoxy-6-(3,7-dimethyl[3H]octyl) 1,4-benzoquinone (azido-Q), was used to study the plastoquinone-protein interaction and to identify the plastoquinone-binding protein in the cytochrome b6-f complex from spinach chloroplasts. When the lipid- and plastoquinone deficient cytochrome b6-f complex is incubated with varying concentrations of azido-Q and illuminated with long wavelength UV light for 7 min at 2 degrees C, the enzymatic activity, assayed after reconstitution with lipid, decreases as the concentration of azido-Q increases. Maximum inactivation (45%) is observed when 30 mol of azido-Q is used per mol of cytochrome f. The extent of the decrease in activity upon illumination correlates with the amount of azido-Q incorporated into the protein. The 50% inactivation is in good agreement with that expected based on the amount of plastoquinone deficiency of the isolated enzyme complex. When the photolyzed, [3H]azido-Q-treated sample is extracted with organic solvent and subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis, radioactivity is found primarily in the Mr = 17,000 subunit. When the enzyme is pretreated with the electron transfer inhibitor 2,5-dibromo-3-methyl-6 isopropylbenzoquinone or 5-n-undecyl-6-hydroxy-4,7-dioxobenzothiazole, significantly less radioactive label is observed in the Mr = 17,000 protein, suggesting that the action sites of these inhibitors are the same or near the plastoquinone-binding site. When the deficient complex is reconstituted with glycolipid prior to the addition of azido-Q, less than 5% inactivation is observed upon photolysis, and the amount of radioactive label on the Mr = 17,000 protein decreases greatly, suggesting that the plastoquinone-binding site is easily masked by glycolipid when endogenous plastoquinone is absent. Plastoquinol 2 apparently competes with azido-Q for the plastoquinone-binding site since it decreases the radioactive label on the Mr = 17,000 protein. PMID- 2912962 TI - Oocytes from the mutant restricted ovulator hen lack receptor for very low density lipoprotein. AB - Hens of the "Restricted Ovulator" (R/O) chicken strain are characterized by the absence of egg-laying and concomitant severe hyperlipidemia due to a single gene defect (Ho, K. J., Lawrence, W. D., Lewis, L. A., Liu, L. B., and Taylor, C. B. (1974) Arch. Pathol. 98, 161-172). However, the underlying biochemical defect has not been identified. Previous studies on receptor-mediated growth of chicken oocytes have led to the characterization of a 95-kDa oocyte plasma membrane receptor that binds very low density lipoproteins (VLDL) (George, R., Barber, D. L., and Schneider, W. J. (1987) J. Biol. Chem. 262, 16838-16847). The current experiments demonstrate the absence of this receptor from R/O oocytes. Ligand binding experiments showed that ovarian membranes from mutant hens failed to display high affinity, saturable, and specific binding of 125I-VLDL. Ligand blotting with 125I-VLDL and Western blotting with polyclonal anti-receptor antibodies visualized the 95-kDa receptor in normal oocytes, but R/O ovarian membranes were devoid of any cross-reactive protein. Finally, plasma clearance of intravenously injected 125I-VLDL was dramatically impaired in R/O in comparison to normal hens, with a concomitant decrease in the radioactivity accumulating in R/O oocytes. These data strongly suggest that the absence of the 95-kDa receptor for VLDL from oocytes is responsible for the R/O phenotype, and that the receptor not only binds VLDL, but also mediates its uptake. This animal model provides a powerful tool for investigations of receptor-mediated growth of chicken oocytes and for the elucidation of regulatory mechanisms in lipid and lipoprotein metabolism of laying hens. PMID- 2912963 TI - Kinetics of p-mercuribenzoate binding to sulfhydryl groups on the isolated cytoplasmic fragment of band 3 protein. Effect of hemoglobin binding on the conformation. AB - Hemoglobin binds to the cytoplasmic domain of band 3 protein (CDB3) at physiologic pH and ionic strength in an oxygen-linked fashion, with deoxyhemoglobin having the higher affinity. The evidence in the literature suggests functional communication between the hemoglobin-binding site on CDB3 and the anion transport sites within the membrane-bound domain of band 3. Since the hemoglobin-binding site is estimated to be over 200 A from the transport domain, the functional communication hypothesis would require the existence of long range, global changes in the CDB3 dimeric quaternary structure consequent to hemoglobin binding. In this report sulfhydryl reactivity toward p-mercuribenzoate is studied in an attempt to identify such long-range conformational changes. Formation of stoichiometric hemoglobin/CDB3 complexes is shown to produce major changes in sulfhydryl reactivity. Since the sulfhydryl pocket of CDB3 is known to lie at the dimeric interface over 100 A from the hemoglobin-binding site, the observed changes in reactivity suggest that hemoglobin complexation induces a global change in quaternary structure of the CDB3 dimer. This change offers a mechanism to explain functional connections between CDB3-binding sites and the anion transport sites on band 3. The existence of such long-range conformational changes would imply that the CDB3 dimer is poised to function as a cytosolic arm or lever in order to modulate the global structure of the porter. PMID- 2912964 TI - Analysis of the proteoglycans synthesized by corneal explants from embryonic chicken. I. Characterization of the culture system with emphasis on stromal proteoglycan biosynthesis. AB - Corneal explants with scleral rims were freshly prepared from day 18 chicken embryos and incubated in vitro for 3 h in the presence of various radioactive precursors. Radiolabeled proteoglycans were isolated from the stromal tissue and culture medium for analysis. Two predominant proteoglycans were identified in corneal stroma. One contains dermatan sulfate and the other contains keratan sulfate; a structural analysis of each is reported in the accompanying paper (Midura, R.J., and Hascall, V.C. (1989) J. Biol. Chem. 264, 1423-1430). A minor keratan sulfate proteoglycan distinct from the major form, a small amount of heparan sulfate proteoglycan, and some sulfated glycoproteins were also detected in stromal extracts. The biosynthesis of the dermatan sulfate proteoglycan was stable in vitro and in ovo, whereas that of the major keratan sulfate proteoglycan was stable only in ovo. Various treatments were tried to maintain a high rate of keratan sulfate synthesis with time in culture. Cooling the corneal explants to 5 degrees C was the only treatment that reduced this decline in keratan sulfate synthesis in vitro to any significant extent. Three major proteoglycans were observed in the culture medium. Two were dermatan sulfate proteoglycan and appeared to be mainly derived from the scleral tissue surrounding the corneal explant. The third proteoglycan contained keratan sulfate. It was smaller in size and lower in charge density compared to the keratan sulfate proteoglycan found in the stroma, but both appeared to have similar core protein sizes. It seems likely that this proteoglycan was synthesized in the stroma and secreted into the medium. A small amount of heparan sulfate proteoglycan and some sulfated glycoproteins were also detected in the medium. PMID- 2912965 TI - Phosphatidylethanol biosynthesis in ethanol-exposed NG108-15 neuroblastoma X glioma hybrid cells. Evidence for activation of a phospholipase D phosphatidyl transferase activity by protein kinase C. AB - 12-O-Tetradecanoylphorbol-13-acetate (TPA) stimulates the release of free choline from intact NG108-15 cells into the medium, without affecting the release of phosphocholine (Liscovitch, M., Blusztajn, J.K., Freese, A., and Wurtman, R.J. (1987) Biochem. J. 241, 81-86). To test the hypothesis that this response reflects activation of cellular phospholipase D, via protein kinase C (Ca2+/phospholipid-dependent enzyme), I examined in NG108-15 cells the biosynthesis of the abnormal phospholipid phosphatidylethanol, produced by phospholipase D in the presence of ethanol by transphosphatidylation. Phosphatidylethanol production was quantitated by measuring the incorporation of phosphatidyl moieties (prelabeled metabolically with [3H]oleic acid) into phosphatidylethanol. The production of phosphatidylethanol in NG108-15 cells was virtually dependent on stimulation by TPA, in a time- and concentration-dependent manner (EC50 = 18 nM). The rate of 3H-phosphatidylethanol formation reached a peak after 10 min of incubation with TPA and declined gradually thereafter. The levels of 3H-phosphatidylethanol in TPA-treated cells were directly related to ethanol concentration in the physiologically attainable range (20-80 mM). Phosphatidylethanol production was activated only by phorbol derivatives that are activators of protein kinase C (i.e. TPA, 4 beta-phorbol-12,13-dibutyrate, and 4 beta-phorbol-12,13-didecanoate) and could be mimicked by a cell-permeant diacylglycerol, 1,2-dioctanoyl-sn-glycerol, in a nonadditive manner. The effect of TPA was inhibited by the protein kinase C inhibitor 1-(5-isoquinolinesulfonyl) 2-methylpiperazine (0.1 mM) by 70% but not by N-(2-guanidinoethyl)-5 isoquinolinesulfonamide. Phosphatidylethanol formation was completely abolished in cells in which protein kinase C was down-regulated by pretreatment of the cells with TPA. These results indicate that phosphatidylethanol biosynthesis in NG108-15 cells depends largely on activation of protein kinase C. In contrast to its effects on the release of free choline and on the accumulation of phosphatidylethanol, TPA did not affect the levels of phosphatidic acid in NG108 15 cells. It is therefore proposed that protein kinase C selectively activates the phosphatidyl transferase activity of phospholipase D, reflecting a signal termination mechanism which may be operative in phospholipase D-mediated signal transduction cascades. PMID- 2912966 TI - Host-range related structural features of the acidic extracellular polysaccharides of Rhizobium trifolii and Rhizobium leguminosarum. AB - Proton nuclear magnetic resonance (1H NMR) and fast atom bombardment mass spectrometric analyses were performed on enzymatically derived oligosaccharides from the acidic excreted polysaccharides (EPS) from representative bacterial strains of the pea-nodulating symbiont, Rhizobium leguminosarum (128C53, 128C63, and 300) and the clover-nodulating symbiont, Rhizobium trifolii (NA-30, ANU843, 0403, TA-1, LPR5035, USDA20.102, and 4S). The results revealed structural similarities and differences between EPS of these two species. Octasaccharide units containing galactose, glucuronic acid, alpha-L-threo-hex-4 enopyranosyluronic acid, and glucose in a molar ratio of 1:1:1:5 were obtained from the EPS of the three R. leguminosarum strains and had the same primary glycosyl sequence and location of pyruvate, acetate, and 3-hydroxybutyrate substituents. About 80% of the galactose residues were acylated with 3 hydroxybutyrate, and there were two acetyl groups per repeating unit distributed between the 2 glucose residues of the main chain-derived sequence of the octasaccharides. In contrast, the R. trifolii strains had varied EPS structures, each of which differed from the common R. leguminosarum EPS structure. The EPS from one group of R. trifolii strains (0403 and LPR5035) most closely resembled the R. leguminosarum EPS but differed in that a lower number of galactose and glucose residues were substituted by 3-hydroxybutyryl and acetyl groups, respectively. The EPS from a second group of R. trifolii strains (ANU843, TA-1, and NA-30) was even more different than the R. leguminosarum EPS. These R. trifolii octasaccharides bore a single acetyl group on O-3 of the glucuronic acid residue. In addition, the level of acylation by 3-hydroxybutyryl groups was 50% of that present in the R. leguminosarum EPS. The remaining two strains of R. trifolii (USDA20.102 and 4S) had very different patterns of acylation to each other and to all of the other strains. The EPS from strain USDA20.102 practically lacked 3-hydroxybutyryl groups and had a unique degree and pattern of acetylation. The oligomers from the EPS of R. trifolii strain 4S completely lacked 3-hydroxybutyryl groups and galactose. The latter EPS contained only one O 1-carboxyethylidene group and had a different degree and pattern of acetylation. Interestingly, these two latter strains differ from the other R. trifolii strains in nodulation rates on rare clover species in the Trifolium cross-inoculation group. Thus, we define several groups of R. trifolii based upon their EPS structures and establish their similarities and distinct differences with the EPS of R. leguminosarum.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2912967 TI - Specific binding of nuclear proteins to the promoter region of a maize nuclear rRNA gene unit. AB - The external spacer region of a nuclear rRNA gene unit of maize was analyzed for binding of nuclear proteins and revealed binding to the promoter region and to the 200-base pair repeat elements upstream of the promoter. The promoter binding site was further characterized by DNase I and exonuclease III foot-printing as well as by gel shift and South-Western experiments, revealing the binding of several proteins. Competition experiments indicate that the protein which interacts with the repeat units also binds to the promoter region. A model for the combined action of both binding regions in the regulation of transcription is presented. PMID- 2912968 TI - Phorbol ester stimulates the hydrolysis of phosphatidylethanolamine in leukemic HL-60, NIH 3T3, and baby hamster kidney cells. AB - Treatment of leukemic HL-60, NIH 3T3, and baby hamster kidney (BHK-21) cells, prelabeled with [2-14C]ethanolamine, with 12-O-tetradecanoylphorbol-13-acetate (TPA), a potent activator of protein kinase C, resulted in increased degradation of both 14C-labeled phosphatidylethanolamine and its alkenyl (plasmalogen) derivate. A half-maximal and a maximal (approximately 3.4-fold) stimulation of ethanolamine phospholipid degradation required 3 and 10-20 nM TPA, respectively. TPA had a similar concentration-dependent stimulatory effect on the hydrolysis of phosphatidylcholine in cells previously prelabeled with [methyl-14C]choline. Increased phospholipid degradation was not accompanied by the formation of lysophosphatidylethanolamine, indicating that a phospholipase A-type enzyme was not involved. About 80% of total water-soluble degradation products was ethanolamine, suggesting that phospholipid hydrolysis was catalyzed by a phospholipase D-type enzyme. Increased formation of ethanolamine with exposure of cells to TPA was observed only after a 10-min lag period. Mezerein, bryostatin, sn-1-oleoyl-2-acetylglycerol, and polymyxin B, all of which mimic the action of TPA on protein phosphorylation in vivo, also stimulated the hydrolysis of ethanolamine phospholipids in HL-60 cells, suggesting that the TPA effect was mediated by protein kinase C. PMID- 2912969 TI - Active and inactive forms of the transition-state analog protease inhibitor leupeptin: explanation of the observed slow binding of leupeptin to cathepsin B and papain. AB - Leupeptin and similar peptide argininal (arginine aldehyde) transition-state analog protease inhibitors exist in three covalent forms in aqueous solution, the leupeptin hydrate (IH), a cyclic carbinolamine form (IC) generated by the addition of the guanidino epsilon N to the aldehydic carbon, and the free aldehyde form (IA). 1H NMR in D2O show their equilibrium concentrations to be 42, 56, and 2% for IH, IC (R and S enantiomers), and IA. The rates of conversion of (formula; see text) were determined by 1H NMR in D2O by trapping IA with semicarbazide. Application of a deuterium isotope effect of 2.8 led to rate constants in H2O for kC of 0.092 min-1 and kD of 0.73 min-1. The equilibrium concentration of IA and rates for kC and kD are then used to explain the lag phase in the inhibition of cathepsin B and papain by leupeptin. Two circumstances are observed. (i) At micromolar concentrations of leupeptin and papain the binding of leupeptin is biphasic with rate constants identical to kD and kC. (ii) At more dilute nanomolar concentrations of total leupeptin and proteases, the observed lag phase for approach to steady-state inhibition (with rate constant k') is now explained by the low values of the koff rate constants (0.072 min-1 for cathepsin B and 0.024 min-1 for papain) together with the extremely low concentrations of the active inhibitor form IA, with k' = kon[IA] + koff. While kon[IA] is slow, the second-order rate constant kon is found to be quite fast, 1.2 x 10(7) M-1 s-1 for cathepsin B and 1.8 x 10(7) M-1 s-1 for papain. Thus, the binding of leupeptin to cathepsin B and papain may show a lag phase, but this is not due to slow binding. PMID- 2912970 TI - Accumulation of unique globo-series glycolipids in PC 12h pheochromocytoma cells. AB - In a previous paper, we reported the presence of a unique globo-series glycolipid as one of the major neutral glycolipid: Gal alpha 1-3Gal alpha 1-4Gal beta 1-4Glc beta 1-1' Cer, in the subcloned PC 12h pheochromocytoma cells (Ariga, T., Yu, R. K., Scarsdale, J. N., Suzuki, M., Kuroda, Y., Kitagawa, H., and Miyatake, T. (1988) Biochemistry 27, 5335-5340). Recently we found that the subcloned PC 12h cells accumulated other unusual neutral glycolipids. In order to characterize these glycolipids, PC 12h cells were subcutaneously transplanted into rats. The induced tumor tissue accumulated four minor neutral glycolipids, which were purified by droplet counter-current, Iatrobeads column, and preparative thin layer chromatographies. These glycolipid structures were determined by fast atom bombardment-mass spectrometry, proton nuclear magnetic resonance spectroscopy, permethylation study, and sequential degradation with various exoglycosidases to be as follows: A, Fuc alpha 1-2Gal alpha 1-3Gal alpha 1- 4Gal beta 1-4Glc beta 1 1'Cer; B, GalNAc beta 1-3Gal alpha 1-3Gal alpha 1- 4Gal beta 1-4Glc beta 1-1'Cer; C, Gal alpha 1-3Gal alpha 1-3Gal alpha 1- 4Gal beta 1-4Glc beta 1-1'Cer; and D, Gal alpha 1-3Gal alpha 1-3Gal alpha 1- 3Gal alpha 1-4Gal beta 1-4Glc beta 1 1'Cer. Glycolipids A and B were tentatively characterized in normal rat small intestine (Breimer, M. E., Hansson, G. C., Karlsson, K.-A., and Leffler, H. (1982) J. Biol. Chem. 257, 557-568; Angstrom, J., Breimer, M. E., Falk, K.-E., Hansson, G. C., Karlsson, K.-A., and Leffler, H. (1982) J. Biol. Chem. 257, 682 688). Glycolipids C and D have not been reported in the literature. PMID- 2912971 TI - Structural determinants of heparin's growth inhibitory activity. Interdependence of oligosaccharide size and charge. AB - The glycosaminoglycan heparin inhibits the growth of several cell types in vitro including smooth muscle cells and rat cervical epithelial cells. The commercially available heparin which has antiproliferative activity is a structurally heterogeneous polymer that undergoes extensive modifications during maturation. In this report we have performed structure-function studies on heparin's antiproliferative activity using three different cell types: both rat and calf vascular aortic smooth muscle cells and rat cervical epithelial cells. The minimal oligosaccharide size requirements for antiproliferative activity were determined for the three cell types by using oligosaccharide fragments of defined length prepared by nitrous acid cleavage and gel filtration and a synthetic pentasaccharide. The size requirements are similar but not identical for the different cell types. Hexasaccharide fragments are antiproliferative for all three cell types but the synthetic pentasaccharide inhibits the growth of only the rat and calf vascular aortic smooth muscle cells. The interdependence between size and charge for antiproliferative activity was investigated using chemically modified oligosaccharides as well as oligosaccharides prepared from heparin and separated into fractions of differing charge by ion-exchange chromatography. There is a strong interdependence between size and charge for antiproliferative activity. For example, increasing the charge of inactive tetrasaccharide fragments by O-oversulfation makes them antiproliferative whereas reducing the charge of active larger fragments causes them to loose their antiproliferative activity. Finally the importance of 2-O-sulfate glucuronic acid moieties for antiproliferative activity was investigated using heparin preparations that lack 2-O-sulfate glucuronic acid. These compounds possess antiproliferative activity indicating that 2-O-sulfate glucuronic acid is not required for antiproliferative activity. PMID- 2912972 TI - Primary structure of the Drosophila laminin B2 chain and comparison with human, mouse, and Drosophila laminin B1 and B2 chains. AB - Laminin, a major component of basement membranes, is a large glycoprotein consisting of three disulfide-bonded subunits, A, B1, and B2. We have isolated and sequenced a Drosophila laminin B2 chain cDNA clone that spans 5737 nucleotides. The deduced amino acid sequence predicts that the mature and nonglycosylated polypeptide has a chain length of 1606 residues (Mr = 178,665). This B2 chain contains 100 half-cystine residues, most of which are located in two cysteine-rich domains, and 11 N-X-S or N-X-T sequences which are potential sites of N-linked glycosylation. The predicted secondary structure reveals the presence of six structurally distinct domains, of which two are mainly alpha helical, two are cysteine-rich with homologous repeats, and two are globular regions. The Drosophila B2 chain is 40.3 and 41.1% identical to the human and mouse B2 chains, respectively, and 29.6, 30.0, and 29.4% identical to the Drosophila, human, and mouse B1 chains, respectively. PMID- 2912973 TI - Amino acid sequence of crayfish troponin I. AB - Troponin I is the actomyosin ATPase inhibitory subunit present in the thin filament regulatory complex. The complete amino acid sequence of crayfish tail muscle troponin I has been determined. The protein is composed of 201 amino acid residues and has a molecular weight of 23,547. The N terminus is blocked, likely by an acetyl group. Crayfish troponin I shows a rather low (20-25%) sequence identity with vertebrate troponin Is as compared to the 60-82% identity within the vertebrate phylum. Similar to vertebrate cardiac troponin I, crayfish troponin I contains a 30-residue-long N-terminal extension. In crayfish troponin I, this segment bears significant sequence homology with the heavy or light chains of particular myosins. The actin-binding domain of crayfish troponin I, which displays 57% sequence homology with vertebrate troponin Is, possesses 2 unusual trimethyllysine residues. The consensus sequence of this domain in five troponin Is is as follows: D-L-R-G-K-F-X-R*-P-X-L-R*-R*-V, where R+ stands for Arg/Lys, R* for Arg/trimethyllysine, and X for any amino acid residue. Troponin I possesses two Ca2+-dependent interactive sites for troponin C; one partly overlaps with the actin binding domain and is highly conserved, and the other, corresponding to the 30-residue-long segment following the N-terminal extension in vertebrate cardiac and crayfish troponin I, is poorly conserved in the different troponin Is. Troponin I also interacts with troponin T. The consensus sequence for the interacting site on troponin I is as follows: h-D- -X-D- -R+-Y-D h-E-h, where h stands for a hydrophobic residue, D- for Asp/Glu, R+ for Arg/Lys, and X for any residue. The five troponin Is further possess one more 15-residue long segment of high sequence identity near the C terminus. Its evolutionary conservation suggests that this domain is involved in protein-protein interaction. PMID- 2912974 TI - Resistance of heparinase-derived heparin fragments to biotransformation. AB - The biotransformation of heparinase-derived heparin fragments was examined via a combined approach using 35S-labeled heparin fragments as well as unlabeled chemically defined heparin fragments. Rats dosed with either [35S]di-, tetra-, hexa-, or octasaccharide fragments (2 mg/kg body weight, intravenously) excreted 63-69% of the injected radioactivity into the urine within 24 h with two-thirds being excreted during the first 6 h. Gel permeation chromatography of the urinary material shows that the tetra- and octasaccharides have undergone minor (approximately 5%) depolymerization whereas no change was observed for the di- and hexasaccharides. No N-desulfation was demonstrated for any of the substances. The hexa- and octasaccharide metabolites present in the urine 24 h after dosing exhibited the same antifactor Xa activity as that of the injected material. A chemically defined trisulfated disaccharide and a hexasulfated tetrasaccharide were prepared and dosed in a similar manner. Only one metabolite was recovered from animals dosed with disaccharide. This compound was characterized by anion exchange chromatography, proton nuclear magnetic resonance spectroscopy, Fourier transform infrared spectrometry, and mass spectrometry and shown to be identical to the injected disaccharide. Five metabolites were isolated from the urine of rats dosed with the hexasulfated tetrasaccharide. The major metabolite, consisting of at least 65% of the total, was characterized as described for the disaccharide and shown to be identical to the injected compound. The remaining material appeared to be disaccharides and, possibly, a tetrasaccharide conjugate. Taken together, our results show that the heparinase-derived heparin fragments are very resistant to biotransformation compared with heparin and endogenous heparin fragments. These fragments may therefore be useful in defining structure activity relationships in vivo. PMID- 2912975 TI - Adrenodoxin with a COOH-terminal deletion (des 116-128) exhibits enhanced activity. AB - Adrenodoxin, purified from bovine adrenal cortex, was subjected to trypsin cleavage to yield a trypsin-resistant form, designated TT-adrenodoxin. Sequencing with carboxypeptidase Y identified the trypsin cleavage site as Arg-115, while Edman degradation indicated no NH2-terminal cleavage. Native adrenodoxin and TT adrenodoxin exhibited similar affinity for adrenodoxin reductase as determined in cytochrome c reductase assays. In side chain cleavage assays using cytochrome P 450scc, however, TT-adrenodoxin demonstrated greater activity than adrenodoxin with cholesterol, (22R)-22-hydroxycholesterol, or (20R,22R)-20,22 dihydroxycholesterol as substrate. This enhanced activity is due to increased affinity of TT-adrenodoxin for cytochrome P-450scc; TT-adrenodoxin exhibits a 3.8 fold lower apparent Km for the conversion of cholesterol to pregnenolone. TT Adrenodoxin was also more effective in coupling with cytochrome P-450(11) beta, exhibiting a 3.5-fold lower apparent Km for the 11 beta-hydroxylation of deoxycorticosterone. In the presence of partially saturating cholesterol, TT adrenodoxin elicited a type I spectral shift with cytochrome P-450scc similar to that induced by adrenodoxin, and spectral titrations showed that oxidized TT adrenodoxin exhibited a 1.5-fold higher affinity for cytochrome P-450scc. These results establish that COOH-terminal residues 116-128 are not essential for the electron transfer activity of bovine adrenodoxin, and the differential effects of truncation at Arg-115 on interactions with adrenodoxin reductase and cytochromes P-450 suggest that the residues involved in the interactions are not identical. PMID- 2912976 TI - Structural determination of a cyclic metabolite of NAD+ with intracellular Ca2+ mobilizing activity. AB - Incubation of NAD+ with extracts from sea urchin eggs resulted in production of a metabolite which could mobilize intracellular Ca2+ stores of the eggs. In this study we present structural evidence indicating that the metabolite is a cyclized ADP-ribose having an N-glycosyl linkage between the anomeric carbon of the terminal ribose unit and the N6-amino group of the adenine moiety. In view of this structure we propose cyclic ADP-ribose as the common name for the metabolite. The purification procedure for the metabolite consisted of deproteinizing the incubated egg extracts and sequentially chromatographing the extracts through three different high pressure liquid chromatography (HPLC) columns. The homogeneity of the purified metabolite was further verified by HPLC on a Partisil 5 SAX column. Using radioactive precursor NAD+ with label at various positions it was demonstrated that the metabolite was indeed derived from NAD+ and that the adenine ring as well as the adenylate alpha-phosphate were retained in the metabolite whereas the nicotinamide group was removed. This was confirmed by 1H NMR and two-dimensional COSY experiments, which also allowed the identification of all 12 protons on the two ribosyl units as well as the two protons on the adenine ring. From the chemical shifts of the two anomeric protons it was concluded that the C-1 carbons of both ribosyl units were still bonded to nitrogen. The positive and negative ion fast atom bombardment mass spectra showed (M + Na)+, (M - H + 2Na)+, (M - H)-, and (M - 2H + Na)- peaks at m/z 564, 586, 540, and 562, respectively. Exact mass measurements indicated a molecular weight of 540.0526 for (M - H)-. This together with the constraints imposed by the results from NMR, radioactive labeling, and total phosphate determination uniquely specified a molecular composition of C15H21N5O13P2. Analysis by 1H NMR and mass spectroscopy of the only major breakdown product of the metabolite after prolonged incubation at room temperature established that it was ADP-ribose, thus providing strong support for the cyclic structure. PMID- 2912977 TI - Free sialooligosaccharides found in the unfertilized eggs of a freshwater trout, Plecoglossus altivelis. A large storage pool of complex-type bi-, tri-, and tetraantennary sialooligosaccharides. AB - Unfertilized eggs of Plecoglossus altivelis (a kind of freshwater trout, "Ayu" in Japanese) were found to contain a relatively large pool of three sialooligosaccharides. These free oligosaccharides were accumulated in the cytoplasm up to concentrations of about 35 ng per egg, which correspond to about 107 micrograms/g. Their structures were determined by a combination of chemical (composition and methylation analysis and Smith degradation) and instrumental (fast atom bombardment-mass spectrometry, secondary ion mass spectrometry, and 400-MHz1H NMR) analyses. The structures established represent a typical type of bi-, tri-, and tetraantennary sialooligosaccharides all of which end with di-N acetylchitobiose structure (-GlcNAc beta 1-4GlcNAc) and alpha -2,3-linked NeuAc at reducing and nonreducing termini, respectively. These data show that these free sialooligosaccharides, which were originally protein-linked components, must be released during oogenesis. Although a specific functional requirement for their release is not known, the occurrence of such free sialooligosaccharides in normal animal cells or tissues has not been previously reported. PMID- 2912978 TI - Loss of a calcium requirement for protein synthesis in pituitary cells following thermal or chemical stress. AB - Ca2+ is required for the maintenance of high rates of translational initiation in GH3 pituitary cells (Chin, K.-V., Cade, C., Brostrom, C.O., Galuska, E.M., and Brostrom, M.A. (1987) J. Biol. Chem. 262, 16509-16514). Following thermal stress at 46 degrees C or chemical stress from exposure to sodium arsenite or 8 hydroxyquinoline, rates of amino acid incorporation in Ca2+-restored GH3 cells were reduced acutely to those of unstressed, Ca2+-depleted control preparations. Sodium arsenite treatment resulted in loss of ability to accumulate polysomes in response to Ca2+. Stressed cells allowed to recover for 2-8 h either with or without Ca2+ in the medium exhibited comparable, increasing rates of amino acid incorporation and the induction of heat shock proteins (hsp). Abolition of the Ca2+-dependent component of translation was proportional to the intensity of the stress. Mild thermal stress (41 degrees C) resulted in the induction of hsp 68 and the retention of Ca2+-dependent protein synthesis; hsp 68 was synthesized in a Ca2+-dependent manner. After arsenite stress, restoration of the Ca2+ requirement for protein synthesis occurred by 24 h, and was preceded by a transitional period during which polysomes accumulated in response to Ca2+ without concomitant increased rates of incorporation. Responses to stress are proposed to include an acute inhibition of normal protein synthesis involving the destruction of Ca2+-stimulated initiation and a protracted period of recovery involving synthesis of the hsp accompanied by Ca2+-independent amino acid incorporation and slowed peptide chain elongation. PMID- 2912979 TI - Ganglioside-specific binding protein on rat brain membranes. AB - A derivative of ganglioside GT1b (IV3NeuAc,II3(NeuAc)2-GgOse4) with an active ester in its lipid portion was synthesized and covalently attached to bovine serum albumin (BSA). The conjugate, having four GT1b molecules per albumin molecule [GT1b)4BSA) was radioiodinated and used to probe rat brain membranes for ganglioside binding proteins. A ganglioside-specific, high affinity (KD = 2-4 nM), saturable (Bmax = 13-20 pmol/mg membrane protein) binding site for 125I (GT1b)4BSA was demonstrated on detergent-solubilized rat brain membranes adsorbed to filters. 125I-(GT1b)4BSA binding was tissue-specific (more than 35-fold greater to brain than to liver membranes) and was nearly eliminated by pretreatment of brain membrane-adsorbed filters with trypsin (1 microgram/ml). Underivatized gangliosides added as mixed detergent-lipid micelles blocked 125I (GT1b)4BSA binding to brain membranes; structurally related GQ1b, GT1b, and GD1b were the most potent (half-maximal inhibition at 70-110 nM), while half-maximal inhibition by other gangliosides (GD3, GD1a, GM3, GM2, and GM1) required 5-20 fold higher concentrations. Other sphingolipids, neutral glycosphingolipids, and glycoproteins were poor inhibitors, and treatment of (GT1b)4BSA with neuraminidase attenuated its binding. Although most phospholipids were noninhibitory, phosphatidylinositol and phosphatidylglycerol inhibited half maximally at 400-600 nM. However, inhibition of 125I-(GT1b)4BSA binding by gangliosides was competitive and reversible while that by phosphatidylinositol and phosphatidylglycerol was not. Ganglioside-protein conjugate binding reveals ganglioside-specific brain membrane receptors. PMID- 2912980 TI - Purification of human transcription factor IIIA and its interaction with a chemically synthesized gene encoding human 5 S rRNA. AB - Transcription factor IIIA (TFIIIA) was purified from cytoplasmic extracts of HeLa cells by developing a simple and efficient procedure employing phosphocellulose under widely differing ionic conditions followed by affinity chromatography on immobilized human 5 S genes. This procedure yielded a fraction containing human TFIIIA activity and a protein of 35 kDa as its major component. Moreover, we succeeded in renaturing the activity of human transcription factor IIIA (hTFIIIA) isolated after preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis and in identifying a polypeptide of 35 kDa with the transcription activity. This value differs from that reported for Xenopus TFIIIA. It could be demonstrated by footprinting analyses that hTFIIIA specifically binds to the internal control region of the human 5 S rRNA gene. The limits of protection slightly differ at the 3' border of the internal control region from those imprinted by Xenopus TFIIIA on the same gene. Comparative footprint analyses of hTFIIIA on the human and frog somatic 5 S rRNA gene, measured in titration, competition, and salt-stability experiments, demonstrated a higher affinity of the human factor to the homologous gene. These results, together with the difference in molecular mass of these functionally analogous proteins, reemphasize the importance of homologous systems for the analysis of mechanisms involved in gene regulation. PMID- 2912981 TI - Site-specific oxidative DNA damage at polyguanosines produced by copper plus hydrogen peroxide. AB - Oxidative DNA damage has been implicated in diverse biological processes including mutagenesis, carcinogenesis, aging, radiation effects, and chemotherapy. We examined the in vitro effect of low concentrations of Cu(II) or H2O2 alone and in combination on supercoiled plasmid DNA. As much as 10(-2) M Cu(II) or 10(-2) M H2O2 alone did not break the DNA. However, a mixture of 10(-6) M Cu(II) plus 10(-5) M H2O2 produced strand breaks and inactivated transforming ability. Strand breakage was proportional to incubation time, temperature, and Cu(II) and H2O2 concentrations. Abasic sites were not detected. Strand breakage was inhibited by metal chelators, catalase, and by high levels of free radical scavengers implying that Cu(II), Cu(I), H2O2, and .OH were involved in the reaction. The extent of DNA strand breakage was not affected by superoxide dismutase indicating that superoxide was not a major contributor to the DNA damage. DNA sequence analysis demonstrated that hot piperidine-sensitive DNA lesions were produced preferentially at sites of 2 or more adjacent guanosine residues. This sequence specificity was observed with Cu(II) plus H2O2 but not with Cu(I) alone. Polyguanosine sequence specificity for DNA damage induction appears to be unique among simple chemical systems. This reaction may be important in mechanisms of oxidative damage in vivo. PMID- 2912982 TI - Epidermal growth factor receptor of the intestinal enterocyte. Localization to laterobasal but not brush border membrane. AB - Interaction of epidermal growth factor (EGF) with its specific receptor (EGFR) was explored in the intact rat small intestine and in highly purified isolated enterocyte membrane preparations. Despite the fact that the EGF ligand is known to be present at physiological concentrations within the intestinal cavity, no significant binding of the ligand to the brush border surface was observed. Instead, binding of EGF to the EGFR was confined to other membrane populations, and correlation of ligand interaction with the laterobasal membranes (LBM) was nearly perfect (p less than 0.001) across a special equilibrium gradient enriched in brush border and LBM but devoid of intracellular membranes. Specific binding to another minor population of intracellular membranes that migrated to a position less dense than typical endoplasmic reticulum-Golgi vesicles on equilibrium gradients was also observed. Immunocytochemical exposure of intestine to EGFR antibody confirmed the localization of the EGFR to LBM and intracellular membranes. As estimated from the intensity of the staining, there may be immunologically active but nonbinding receptor species in the intracellular membrane compartment. Thus, despite the secretion of EGF into the intestinal lumen, the growth and maturational effects of EGF probably result from a specific interaction between EGF and EGFR solely at the laterobasal surface of the enterocyte. The functional role of the intracellular membrane species of EGFR, which remains to be established, may involve a source of inactive receptor that can be rapidly recruited and transferred to the LBM surface under changing environmental conditions. PMID- 2912983 TI - Characterization of a receptor for C5a anaphylatoxin on human eosinophils. AB - The complement anaphylatoxin peptide C5a is well known to activate human polymorphonuclear leukocytes through receptor-mediated processes. C5a has also been reported to activate eosinophils for both chemotaxis and hexose uptake. We characterized the receptor molecule for human C5a on human eosinophils and compared it with the receptor on human neutrophils. At 4 degrees C, uptake of 1 nM 125I-C5a reaches equilibrium within 10 min on both cell types. Binding of 125I C5a occurs over a concentration range comparable to that which stimulates lysosomal enzyme release and hexose uptake in both cell types. Scatchard analyses of the data indicate the presence of two receptor populations on eosinophils; a high affinity receptor with 15,000-20,000 sites/cell and a Kd of 3.1 +/- 0.6 x 10(-11) M, and a low affinity receptor with approximately 375,000 sites/cell and a Kd of 1 x 10(-7) M. Parallel experiments with neutrophils indicate the presence of a single receptor population with approximately 90,000 sites/cell and a Kd of 4.8 +/- 0.1 x 10(-10)M. The eosinophil receptor molecule was further characterized by covalently cross-linking 125I-C5a to cells followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the solubilized material. Autoradiography indicates the presence of a dominant C5a-eosinophil receptor complex with an apparent mass of 60-65 kDa. The corresponding neutrophil-C5a receptor complex has an apparent mass of 50-52 kDa as observed by others. When the cross-linked 125I-C5a-receptor complex was treated with cyanogen bromide, different patterns were observed on sodium dodecyl sulfate-polyacrylamide gel electrophoresis for neutrophils and eosinophils. Thus, human eosinophils have a receptor for C5a anaphylatoxin which appears to be distinct from the C5a receptor present on human neutrophils. PMID- 2912984 TI - Analysis of the binding of high mobility group protein 17 to the nucleosome core particle by 1H NMR spectroscopy. AB - The binding of high mobility group (HMG) protein 17 to the nucleosome core particle has been studied in D2O solution using 1H NMR at 500 MHz. Spectra were obtained for purified HMG 17, purified nucleosome core particles, and the reconstituted HMG 17-nucleosome core particle complex at 0.1, 0.2, 0.3, and 0.4 M NaCl. Subtraction of the core particle spectra from spectra of the core particle reconstituted with HMG 17 demonstrated those regions of HMG 17 which interact with the nucleosome at different ionic strengths; the resonance peaks of interacting groups are broadened due to their restricted mobility. At 0.1 M NaCl, the mobility of all the amino acid side chains of HMG 17 was restricted, indicating complete binding of HMG 17 to the much larger nucleosome core particle. At 0.2 M NaCl most of the amino acids were free with the exception of arginine and proline which are confined to or predominant in the basic central region of HMG 17. These amino acids were completely free only at 0.4 M NaCl. We conclude that the entire HMG 17 molecule interacts with the nucleosome core particle at physiological ionic strength. The acidic COOH-terminal region of HMG 17 is released from interaction with the core histones at an NaCl concentration between 0.1 and 0.2 M and so binds weakly at physiological ionic strength. The basic central region binds more strongly to the core particle DNA, being completely released only at much higher ionic strength, between 0.3 and 0.4 M NaCl. PMID- 2912985 TI - Adrenal glucocorticoids regulate adipsin gene expression in genetically obese mice. AB - Adipsin expression at the protein and mRNA levels is greatly reduced in several distinct syndromes of obesity in the mouse: genetic obesity due to the db/db and ob/ob genes, and a chemically induced model secondary to neonatal exposure to monosodium glutamate. We considered first the possibility that the adipsin gene might be identical to the db or ob locus and the lowered expression of this protein might result from a mutation in this gene. We show here that the adipsin structural gene is located on chromosome 10 and hence is physically distinct from any obesity genes so far identified in the mouse. A major role for the adrenal gland and adrenal glucocorticoids in the aberrant regulation of adipsin in these models of obesity is indicated by several experiments. Adrenalectomy of the ob/ob mouse raises the circulating levels of adipsin protein and the amount of this mRNA in epididymal fat pads (5-fold), although neither is increased to the levels seen in lean controls. Exogenous administration of corticosterone completely blocks the effects of adrenalectomy on adipsin, suggesting that the effect of this endocrine ablation is through reduction of adrenal glucocorticoids. Corticosterone administration also causes suppression in the levels of adipsin mRNA and protein in lean mice, although this decrease is never as severe as that seen in obese mice. The effect of exogenous corticosterone in lean mice occurs within 2 days and hence is not secondary to the obesity which these hormones eventually elicit. These results indicate that glucocorticoids can regulate adipsin expression in vivo and strongly suggest that the hyperglucocorticoid state seen in certain obese models plays a significant role in lowering adipsin mRNA and protein levels. Quantitative analysis of these experiments suggests that other as yet unknown neuroendocrine factors also function to suppress adipsin in obesity. PMID- 2912986 TI - Overexpression of a 123-kDa anion transport inhibitor binding protein and two cytoskeleton proteins in Drosophila Kc cell variants resistant to disulfonic stilbenes. AB - Drugs of the disulfonic stilbene class, which inhibit anion transport in the cell membrane in many cell types, have been found to inhibit anion transport and cell growth in Drosophila Kc cells. Cell variants selected by a stepwise selection protocol for the ability to grow in the presence of the disulfonic stilbenes are severalfold resistant to growth inhibition by the drugs. Both the resistant populations and a cloned cell line show dramatic overexpression of three polypeptides. The most highly overproduced protein is a 123-kDa plasma membrane protein which binds the reversible anion transport inhibitor, flufenamic acid, in a protection biotinylation experiment. The 123-kDa putative anion transport protein copurifies with, and immunologically cross-reacts with, two detergent insoluble cytoskeleton proteins of 46- and 62-kDa molecular weight, which are each overexpressed more than 8-fold in the variants. Resistance to growth inhibition by the disulfonic stilbenes and amplified expression of the 123-, 62-, and 46-kDa proteins are simultaneously lost over a period of 30 weeks in the absence of selective conditions, suggesting that the function of the overproduced polypeptides is related to growth control in Drosophila cells. PMID- 2912987 TI - Identification of proteolytic cleavage sites in the conversion of profilaggrin to filaggrin in mammalian epidermis. AB - Profilaggrin consists of multiple filaggrin domains joined by linker segments which are removed during proteolytic conversion to filaggrin. Analysis of tryptic peptides of filaggrin defined a 26-residue linker segment when aligned on the amino acid sequence of one repeat unit of mouse profilaggrin deduced from a cDNA sequence (Rothnagel, J. A., Mehrel, T., Idler, W. W., Roop, D. R., and Steinert, P. M. (1987) J. Biol. Chem. 262, 15643-15648). Two types of linker segments were distinguished by their different susceptibility to thermolysin and by the presence of a Phe-Tyr-Pro-Val sequence in only one type. These data led to a model of profilaggrin in which the two types of linker segments alternate along the length of profilaggrin. This model provides a structural basis for the two stages of proteolytic processing seen in vivo. In the first stage intermediates accumulate which have several filaggrin domains still joined by linker segments lacking Phe-Tyr-Pro-Val. In the second stage, the other linker segments are cleaved and mature filaggrin domains are released. Proteolytic activity with specificity consistent with first stage cleavage was partially purified from rat epidermis. Chymostatin inhibited both the in vitro enzymatic activity and the processing of profilaggrin in a cultured rat keratinocyte cell line. The products formed in vitro were 3-5 kDa larger than intermediates produced in vivo, suggesting that the linker segments are cleaved at one end only. This implies the existence of a third protease which completes the removal of the linker segments. PMID- 2912988 TI - Regulation of beta-galactoside alpha 2,6-sialyltransferase gene expression by dexamethasone. AB - The hepatic acute phase response is accompanied by increased levels of Gal beta 1 4GlcNAc alpha 2,6-sialyltransferase activity in liver and in circulation. Previous studies suggested that cytokines and glucocorticoids mediate the induction of this sialyltransferase activity. In this study the regulation of sialyltransferase expression by dexamethasone in H35 rat hepatoma cells is assessed by Northern hybridization and enzyme activity assays. Exposure of H35 cells to 1 microM dexamethasone for 24 h causes a 3-4-fold enrichment of sialyltransferase mRNA and a corresponding increase in enzymatic activity. The induction of sialyltransferase mRNA begins within 3 h of dexamethasone treatment and reaches a plateau within 24 h. Sialyltransferase mRNA induction is dose dependent; the minimum concentration of dexamethasone necessary for induction is 10(-8) M, and induction was maximal at 10(-6) M. Induction is sensitive to actinomycin D, suggesting that regulation may be exerted by altering the rate of mRNA synthesis. Puromycin and cycloheximide are ineffective in blocking induction, suggesting that de novo protein synthesis is not required for induction. Finally, dexamethasone alone is sufficient for maximum induction of sialyltransferase mRNA. In contrast, maximal induction of alpha 1-acid glycoprotein, a well studied hepatic acute phase reactant, requires both dexamethasone and cytokines, implying that different pathways exist for the induction of participants in the acute phase response. PMID- 2912989 TI - Semenogelin, the predominant protein in human semen. Primary structure and identification of closely related proteins in the male accessory sex glands and on the spermatozoa. AB - The predominant protein in human semen, semenogelin, was characterized by lambda gt11 clones isolated from a seminal vesicular cDNA library. One clone, carrying a cDNA insert of 1606 nucleotides and a polyadenylated tail, coded for the entire semenogelin precursor. An open reading frame of 1386 nucleotides encodes a signal peptide and the mature protein of 439 amino acid residues, in which residues 85 136 are identical with a previously characterized semenogelin fragment. The polypeptide chain displays a most conspicuous region of internal sequence homology where 46 of the 58 amino acid residues at positions 259-316 are repeated at positions 319-376. An abundant seminal vesicular transcript of 1.8 kilobases (kb) codes for semenogelin. Two additional transcripts, one seminal vesicular 2.2 kb species and one epididymal 2.0-kb species, code for related proteins that have a close structural relationship as well as antigenic epitopes in common with semenogelin. Semenogelin and the semenogelin-related proteins are the major proteins involved in the gelatinous entrapment of ejaculated spermatozoa. Antigenic epitopes common to these proteins are localized to the parts of the spermatozoa involved in locomotion. The spermatozoa become progressively motile as the gel-forming proteins are fragmented by the kallikrein-like protease, prostate-specific antigen, and the gel dissolves. PMID- 2912990 TI - Perioperative red blood-cell transfusion. PMID- 2912991 TI - The use of dynamic electromyography to evaluate motor control in the hands of adults who have spasticity caused by brain injury. AB - A dynamic electromyographic analysis of grasp and release, performed on forty eight upper extremities of forty-two adults who had had injury to the brain causing spasticity, showed volitional motor control of the finger flexors in 80 per cent and active extension of the fingers in 60 per cent. The flexor pollicis longus showed volitional control in 75 per cent of the hands and the extensor pollicis longus showed active control in 50 per cent. The extensor carpi radialis longus acted as an appropriate stabilizer of the wrist in 85 per cent of the extremities. Fourteen muscles had out-of-phase activity that could not be detected on clinical examination. The position of the elbow did not appreciably influence the electromyographic pattern of motor control in the hand. PMID- 2912992 TI - Development of a synovial cyst after arthroscopy of the shoulder. A brief note. PMID- 2912993 TI - Extension of monostotic Paget disease from the femur to the tibia after arthrodesis of the knee. A case report. PMID- 2912994 TI - Generalized enchondromatosis. A case report. PMID- 2912995 TI - Gaucher hemorrhagic cyst of bone. A case report. PMID- 2912996 TI - Emergency transport and positioning of young children who have an injury of the cervical spine. The standard backboard may be hazardous. AB - In ten children who were less than seven years old, an unstable injury of the cervical spine was found to have anterior angulation or translation, or both, on initial lateral radiographs that were made with the child supine on a standard flat backboard. In all ten patients, extension was the proper position for reduction of the injury of the cervical spine. Young children have a large head in comparison with the rest of the body. When a young child is positioned on a standard backboard, the neck may be forced into relative kyphosis. Supine and upright lateral radiographs that were made of seventy-two children who did not have a fracture also demonstrated more relative cervical kyphosis in younger children when they were in the supine position. Calculations from anthropometric data documented disproportionate rates of growth of the head and the chest. The circumference of the head grows logarithmically, but the circumference of the chest grows linearly. This disproportionate growth causes young children to have a relatively large head. When they lie supine, the neck is flexed. To prevent undesirable cervical flexion in young children during emergency transport and radiography, a standard backboard can be modified to provide safer alignment of the cervical spine. This can be accomplished by the use of a recess for the occiput to lower the head or of a double mattress pad to raise the chest. PMID- 2912997 TI - Low incidence of deep-vein thrombosis after cementless total hip replacement. PMID- 2912998 TI - Pain dysfunction syndromes. Teaching physicians how to recognize and treat them. PMID- 2912999 TI - Correlation of the findings of magnetic resonance imaging with those of bone biopsy in patients who have stage-I or II ischemic necrosis of the femoral head. AB - A prospective study was undertaken to determine the diagnostic accuracy of magnetic resonance imaging in the evaluation of a symptomatic hip for which a diagnosis of early ischemic necrosis of the femoral head was suspected. Fifteen patients (sixteen symptomatic hips), for whom the findings of magnetic resonance imaging were consistent with a diagnosis of osteonecrosis of the femoral head, had a core decompression and a biopsy of the contents of the core. Preoperative magnetic-resonance imaging was useful for planning which segment of the femoral head should be biopsied. Plain radiographs and tomograms of the hips were also made. On the basis of the plain radiographs, ten hips were determined to have Stage-I findings and six hips, Stage-II ischemic necrosis, according to the system of Ficat and of Arlet and Ficat. Histological study revealed evidence of necrosis in all of the biopsy specimens of bone. We concluded that findings of magnetic resonance imaging that are characteristic of osteonecrosis correlate well with the results of biopsies of bone in patients who have an early stage of ischemic necrosis. Magnetic resonance imaging is a highly sensitive and specific method for both the diagnosis and the location of Stage-I and Stage-II osteonecrosis. PMID- 2913000 TI - Intraoperative autologous transfusion in orthopaedic patients. AB - The cases of 175 consecutive patients who had intraoperative autologous transfusion during revision total hip arthroplasty, an elective operation on the spine, repair of trauma to the spine, or open reduction of a fracture of the acetabulum were reviewed to evaluate the applicability of this technique in orthopaedic operations. A separate group of forty-one consecutive patients who had open reduction of a fracture of the acetabulum or the spine before the introduction of the autotransfuser was reviewed and compared with the group that had autotransfusion. An autologous blood predeposit program was used for twenty five of fifty-two patients who had a procedure on the hip and for fifty-one of fifty-five patients who had an elective procedure on the spine. The mean rate of red blood-cell salvage using the autotransfuser was 60 per cent over-all. The mean transfusion requirements were significantly less (p less than 0.001) in all groups of patients in whom the autotransfuser was used. Use of the autotransfuser reduced the mean requirement for banked blood in patients who had a fracture of the acetabulum from 3.8 to 2.3 units per patient, and significantly reduced the mean need for banked blood in individuals who had trauma to the spine from 2.7 to 1.8 units per patient (p less than 0.01). The use of prebanked autologous blood further reduced the mean requirement for homologous blood from 2.4 to 0.8 unit per patient in those who had revision total hip arthroplasty (p less than 0.005), and from 3.6 to 0.4 unit per patient in those who had an elective procedure on the spine (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2913001 TI - Spinal fusion augmented by luque-rod segmental instrumentation for neuromuscular scoliosis. AB - Seventy-four patients who had deformity of the spine secondary to a neuromuscular disorder were treated using posterior fusion with Luque-rod segmental instrumentation. The mean curve was 73 degrees preoperatively and 38 degrees postoperatively. The mean loss of correction was 4 degrees at an average duration of follow-up of forty-two months (range, 2.0 to 7.3 years). Complications included one death, three deep wound infections, two pressure sores, six sets of broken rods, and one instance of distal rotation and migration of the rod. There were no major perioperative neurological complications. Failure of instrumentation occurred more frequently with 3/16-inch (4.8-millimeter) diameter than with 1/4-inch (6.4-millimeter) diameter stainless-steel rods. There was a tendency for cephalad progression of deformity when the fusion ended cephalad at or below the fourth thoracic vertebra. We concluded that Luque-rod segmental instrumentation with posterior spinal fusion is an effective treatment for patients who have neuromuscular scoliosis. PMID- 2913002 TI - The pathological anatomy of claw and hammer toes. AB - We sought to determine the optimum surgical treatment of claw and hammer toes (except for the hallux) on the basis of the specific pathological anatomy of each type of deformity. We dissected thirty-three fresh-frozen specimens that had been obtained from below-the-knee amputations. The specimens included ten normal feet, fourteen feet that had claw toes, six feet that had hammer toes, and three feet that had an uncategorized deformity. The contributions of abnormalities of the skin, tendons, joint capsule, and collateral ligaments to deformity of the metatarsophalangeal and proximal interphalangeal joints were determined by sequential sectioning of all of those soft-tissue components. Any alteration in the range of motion of the joints was recorded after each stage of the dissection. The findings of this study suggested that surgical correction of claw and hammer toes may necessitate more extensive sectioning of the soft tissues than had previously been believed. PMID- 2913003 TI - Size of the femoral head and acetabular revision in total hip-replacement arthroplasty. AB - Fifty-nine revisions that were done for aseptic acetabular loosening after 6,128 total hip arthroplasties for degenerative arthritis or traumatic arthritis were studied. These revisions were in forty-four (approximately 1 per cent) of 4,576 hips that had a twenty-two-millimeter femoral-head component, in two of 520 that had a twenty-eight-millimeter femoral-head component, and in thirteen (approximately 2.5 per cent) of 487 that had a thirty-two-millimeter femoral-head component. Therefore, the thirty-two-millimeter femoral component was associated with the highest rate of acetabular revision (p less than 0.001). The dimensions of the acetabular wall were thinner in the hips that had the thirty-two millimeter component than in those that had the twenty-two-millimeter component (p less than 0.05). Multivariate analysis demonstrated a significantly increased risk of acetabular loosening in men and in patients who were less than sixty years old. PMID- 2913005 TI - One-stage anterior cervical decompression and posterior stabilization with circumferential arthrodesis. A study of twenty-four patients who had a traumatic or a neoplastic lesion. AB - Twenty-four patients had a combined anterior cervical decompression and posterior stabilization with circumferential spinal arthrodesis for treatment of either a tumor or an injury. The indication for operation was a fixed kyphosis and an incomplete neurological deficit or cervical instability. All but two patients had substantial improvement, having regained strength or had a reduction in the deformity, or both. The two exceptional patients, both of whom were quadriparetic, had no change. The operation is formidable and requires an average of 6.9 hours of general anesthesia; however, its use is justified in patients who have the appropriate indications. PMID- 2913004 TI - In situ arthrodesis without decompression for Grade-III or IV isthmic spondylolisthesis in adults who have severe sciatica. AB - Eight adults who had back pain and sciatica that was caused by Grade-III or IV isthmic spondylolisthesis of the fifth lumbar vertebra on the sacrum were treated consecutively by in situ arthrodesis without decompression. The anterior displacement of the fifth lumbar vertebra averaged 82 per cent (range, 66 to 118 per cent). The length of follow-up averaged 5.5 years (range, two to fourteen years). All of the arthrodeses resulted in a solid fusion and excellent relief of both the back pain and the sciatica. All of the preoperative neurological deficits resolved, with the exception of a decreased or absent Achilles-tendon reflex in two patients. There were no complications, and all of the patients returned to their preoperative occupations. PMID- 2913006 TI - Intraoperative autologous transfusion in revision total hip arthroplasty. AB - The records of ninety-eight patients (100 hips) who had revision total hip arthroplasty were reviewed to evaluate the efficacy of intraoperative autologous transfusion in reducing homologous blood-transfusion requirements. In the fifty hips in the study group, a mean of 685 milliliters of autologous blood, or 47 per cent of the estimated loss of blood, was transfused intraoperatively. During the entire course of hospitalization, the mean of the total homologous blood transfusion requirements was 795 milliliters in thirty-nine study-group patients, compared with 1160 milliliters in forty-six control-group patients who did not have autologous transfusion. This difference was statistically significant (p less than 0.029). Eleven patients in the study group and four patients in the control group did not receive homologous blood. Over-all, the use of intraoperative autologous transfusion was directly responsible for a 42 per cent reduction in the total amount of homologous blood that was transfused. PMID- 2913007 TI - The deleterious effects of drying on articular cartilage. AB - Knee joints of mature rabbits were exposed to room air for periods of time ranging from thirty minutes to one hour in an attempt to mimic the human situation in the operating room. The animals were killed after the joint had been closed and activity in a cage had been allowed for twenty-four hours. When the animal was killed, cartilage was removed and was incubated with radioactive proline for four hours before light microscopy autoradiographs were made. Other samples were prepared for study by electron microscopy. The results in the animals that were killed immediately after the cartilage was exposed to room air and in those that were killed twenty-four hours after closure of the joint were identical. Both the ultrastructural and the autoradiographic findings indicated that the entire thickness of the articular cartilage was necrotic after sixty minutes of drying. Forty-five minutes of drying produced complete necrosis of the cartilage in half of the animals. In the other half, some cells survived, although many areas of the cartilage had complete necrosis, top to bottom. Thirty minutes of drying produced patchy necrosis that extended only to the middle zone of the cartilage. In joints that were exposed to room air for one hour, necrosis of the chondrocytes was completely prevented by irrigating the joint every five minutes with Ringer lactate solution. PMID- 2913009 TI - Interdisciplinary quality assurance. PMID- 2913010 TI - Clinical laboratory and nursing personnel: collaboration in improving patient care. PMID- 2913008 TI - Supracondylar-intercondylar fractures of the femur. Treatment by internal fixation. AB - The records on fifty-two supracondylar-intercondylar fractures of the femur were reviewed twenty to 120 months after injury. More than one-third of the fractures had been open. All of the fractures were treated in a single trauma center, using: (1) a single lateral incision, (2) internal fixation with ASIF interfragmentary screws and plates, (3) bone-grafting of comminuted metaphyseal segments, (4) impaction of comminuted metaphyseal segments in osteoporotic elderly patients, and (5) repair of any associated torn ligaments and patellar fractures. Postoperatively, early active motion of the knee was encouraged, and for selected patients a brace was used only to protect the repair of associated disruptions of ligaments or of the extensor mechanism. The fractures were classified by the ASIF system, with C1 being a simple Y pattern, C2 having additional supracondylar comminution, and C3 having intra-articular comminution. The final results were rated using the system that was described by Neer et al. for fractures of the distal end of the femur. The average time between the operation and full weight-bearing (healing) was 13.6 weeks and ranged from 12.3 weeks for C1 fractures (as graded using the ASIF classification) to 15.4 weeks for C3 fractures. The average final arc of motion of the knee was 107 degrees, ranging from 113 degrees for C1 fractures to 99 degrees for C3 fractures. C1 fractures had a better outcome (92 per cent excellent and good results) than did C2 and C3 fractures (77 per cent excellent and good results). Two amputations and one arthrodesis were done to treat infection, and infection accounted for three of the four poor results. Age did not influence the final results, although elderly patients had a longer period of hospitalization. Supracondylar intercondylar fractures of the femur should be analyzed separately from other fractures of the distal end of the femur because of their intra-articular involvement and associated ligamentous injuries and patellar fractures. Rigid internal fixation permits early functional rehabilitation of the patient and decreases the incidence of malunion, non-union, and loss of fixation. PMID- 2913012 TI - Quality, standards, and criteria: a physician and nurse perspective. PMID- 2913011 TI - A multidisciplinary approach: assuring quality of care for the diabetic client. PMID- 2913013 TI - Multidisciplinary QA in a critical care unit. PMID- 2913014 TI - Implementing an interdepartmental QA program in a small rural hospital. PMID- 2913016 TI - Multidisciplinary discharge screen. PMID- 2913015 TI - Utilization management: improving patient care while maintaining cost control. PMID- 2913017 TI - Preoperative antibiotic administration: a case for interdisciplinary monitoring. PMID- 2913018 TI - Outcome standards: compliance is possible. PMID- 2913019 TI - Administering nursing support services based on perceptions about quality. PMID- 2913020 TI - Education, sharing, and visibility promote nursing QA. PMID- 2913021 TI - A rapid serum neutralization test in microplates for the detection of antibodies to hog cholera virus. AB - The fluorescent antibody serum neutralization (FASN) test for the detection of antibodies to hog cholera virus was developed utilizing 96-well and Terasaki microplates. This microtechnique, especially when performed in Terasaki plates, offers some advantage if compared with conventional FASN in coverslip cell cultures, being easier and more rapid, saving of reagents and allowing simple microscopic observation. PMID- 2913022 TI - Surveillance of invasive Streptococcus pneumoniae infection in Quebec, Canada, from 1984 to 1986: serotype distribution, antimicrobial susceptibility, and clinical characteristics. AB - Four hundred and sixty-eight strains of Streptococcus pneumoniae isolated from blood or normally sterile body fluids in 14 Quebec, Canada, hospitals between 1 July 1984 and 31 December 1986 were serotyped, their susceptibilities to antimicrobial agents were determined, and the laboratory data were correlated with the clinical information. The distribution pattern of the serogroups and serotypes was similar to that observed previously in Quebec and to that in other parts of Canada and in the United States. No regional variation was observed. The distribution of serogroups and serotypes was different in pediatric patients (less than 18 years old) when compared with that of adults (P less than 0.001). Overall, 94% of the strains were represented in 23-valent vaccine. The total mortality rate was 12.8% and increased with age: 1.6% in pediatric patients, 14.8% in patients 18 to 64 years old, and 31% in those greater than or equal to 65 years old (P less than 0.001). In patients 18 to 64 years old, the mortality rate was higher when an underlying condition that could have justified prior vaccination was present (P = 0.008). In patients greater than or equal to 65 years old, the mortality rates were similar in those with and those without underlying conditions, suggesting that vaccine use in all patients greater than or equal to 65 years old might be appropriate. Only six patients had received pneumococcal vaccine before infection. Only 15 strains (3.2%) were moderately susceptible or resistant to one or more of the antimicrobial agents tested. Six strains were moderately susceptible to penicillin G, and none was fully resistant. PMID- 2913023 TI - Monoclonal antibody solution hybridization assay for detection of human immunodeficiency virus nucleic acids. AB - In this report we describe a novel, nonisotopic hybridization assay for the measurement of viral RNA in biological samples. The assay involved a solution phase reaction between a biotinylated DNA probe and RNA target sequences. Labeled hybrids were detected in an immunoreaction by using a solid-phase anti-biotin antibody and an enzyme-labeled monoclonal antibody specific for DNA-RNA hybrids. This monoclonal antibody solution hybridization assay was compared with an antigen-capture immunoassay for the detection of human immunodeficiency virus in 436 cell culture samples from 60 seropositive patients. The sensitivity and specificity of the hybridization assay were 93.5 and 94.6%, respectively. Detection of human immunodeficiency virus solely by hybridization in the initial sample but not subsequent samples from seven cultures may reflect detection of virus that was present in the patients' lymphocytes but did not replicate in vitro. Since the assay method is adapatable to the detection of either RNA or DNA, it could provide a means for the detection of a wide range of viral nucleic acids. PMID- 2913024 TI - Antigenically variable Borrelia burgdorferi isolated from cottontail rabbits and Ixodes dentatus in rural and urban areas. AB - Spirochetes were isolated from 71 subadult Ixodes dentatus removed from cottontail rabbits captured in Millbrook, N.Y., and in New York, N.Y. Spirochetes were also cultured from kidney tissues of six rabbits. While all isolates reacted with monoclonal antibody H9724, which identifies the spirochetes as borreliae, more than half did not bind with antibody H5332 and even fewer reacted with H3TS, both of which were produced to outer surface protein A of Borrelia burgdorferi. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis protein profiles of three isolates differed from one another and from all previously characterized B. burgdorferi strains from humans, ticks, and wildlife in North America. The 12 periplasmic flagella that originated subterminally from each pointed end of a rabbit Borellia isolate contrasted with the 11 or fewer flagella for B. burgdorferi reported previously from North America. Although DNA homology and restriction endonuclease analysis also revealed differences among a rabbit kidney isolate, an I. dentatus isolate, and B. burgdorferi B31, similarities were sufficient to lead us to conclude that the borreliae in rabbits and I. dentatus are B. burgdorferi. Enzyme-linked immunosorbent assay titers of sera from humans with diagnosed Lyme disease to rabbit tick B. burgdorferi were often similar to one another and to those recorded for a reference B. burgdorferi strain. PMID- 2913025 TI - Phenotypic characterization and DNA relatedness in human fecal isolates of Aeromonas spp. AB - Phenotypic characteristics were used to identify 189 Aeromonas strains isolated from human feces. One hundred forty-two of these strains were placed in 11 DNA hybridization groups, and the genetic and phenotypic data were compared. According to the criteria of Popoff, 66% of the strains were identified as Aeromonas caviae, 18% were identified as A. sobria, and 16% were identified as A. hydrophila. Some biochemical characteristics differed from the criteria of Popoff; 19 of 40 (48%) of tested strains were encapsulated, 42 of 124 (34%) of A. caviae strains were nonmotile, and all A. sobria strains were resistant to KCN. Gas production from D-glucose was temperature dependent; 11 of 64 (17%) A. hydrophila and A. sobria strains produced gas only at 22 degrees C. Of 142 Aeromonas strains, 57% belonged to hybridization group 4, 25% belonged to group 8, 11% belonged to group 1, 4% belonged to group 5A, 2% belonged to group 3, and 1% belonged to group 2. Of 26 strains phenotypically identified as A. hydrophila, 8 (31%) were in hybridization group 8, which contains strains of the new species A. veronii. It therefore appears that our ability to identify Aeromonas strains phenotypically is not sufficiently specific. Either additional definitive biochemical markers must be found or phenotypic identification, at least for some Aeromonas groups, must be regarded as only presumptive. PMID- 2913027 TI - Evaluation of NCS rapid plasma reagin card test, a new screening kit for syphilis. AB - Agreements in qualitative and quantitative test results between the recently marketed NCS rapid plasma reagin card test (NCS Diagnostics Corp.) and the Macro Vue rapid plasma reagin 18-mm circle card test (Hynson, Westcott and Dunning) were 99.2 and 99.1%, respectively, indicating the NCS RPR card test to be an acceptable alternative procedure for the serodiagnosis of syphilis. PMID- 2913026 TI - Passive hemagglutination test for detection of antibodies to human immunodeficiency virus type 1 and comparison of the test with enzyme-linked immunosorbent assay and Western blot (immunoblot) analysis. AB - A passive hemagglutination test (PHA) was developed for detecting antibodies to human immunodeficiency virus type 1 (HIV-1) utilizing sheep erythrocytes cross linked with purified envelope glycoprotein (gp160) of HIV-1. In an analysis of 216 human serum samples, 100% correlation was observed in 86 reactive and 124 nonreactive serum samples between PHA and commercial enzyme-linked immunosorbent assays and Western blot (immunoblot) analysis. Serum samples from gp160-immunized chimpanzees also reacted equally well in PHA. The test is simple, rapid, and inexpensive, thus providing an alternate, quick method of detecting HIV antibodies. These advantages and the thermal stability of the reagents that are used make this an attractive alternative for detecting prior exposure of individuals to HIV-1. PMID- 2913028 TI - Bacteremia and urinary tract infection associated with CDC group Vd biovar 2. AB - A case of urinary tract infection and bacteremia caused by CDC group Vd biovar 2 in a 23-year-old woman with Hodgkin's disease is described. This is the first report of CDC group Vd biovar 2 isolated from a clinical specimen and considered as a pathogen. Detailed antimicrobial susceptibility data are presented. PMID- 2913029 TI - Enzymatic extraction and spectral analysis of the chromophore from cell walls of nutritionally deficient streptococci. AB - We demonstrated by spectral analysis a method to enzymatically cleave the chromophore precursor from nutritionally deficient streptococcal cell walls by treatment with lysozyme. The peak absorbances without and with lysozyme pretreatment were 511.4 +/- 2.02 nm and 513.1 +/- 0.69 nm, respectively. Extraction yields varied among strains and were found to be growth phase dependent. A secondary peak of absorbance (mean of 477 nm) was found in only five of eight strains. The chromophore at a neutral pH undergoes a reaction with phenol consistent with that of a furan, indicating its carbohydrate composition. PMID- 2913030 TI - Detection of pathogenic Yersinia enterocolitica by using congo red-magnesium oxalate agar medium. AB - A Congo red-magnesium oxalate agar medium was developed to detect expression of virulence-associated calcium dependency and Congo red absorption in Yersinia enterocolitica. Of the 157 pathogenic serotypes tested, 119 (75.8%) were positive; 98% of nonpathogenic serotypes and strains of three other Yersinia species were negative. PMID- 2913031 TI - Endocarditis caused by relatively penicillin-resistant Stomatococcus mucilaginosus. AB - We report a case of Stomatococcus mucilaginosus endocarditis in which the isolate was relatively resistant to penicillins and cephalothin. The patient was treated successfully with vancomycin and valve replacement. PMID- 2913032 TI - Flavimonas oryzihabitans (Pseudomonas oryzihabitans; CDC group Ve-2): an emerging pathogen in peritonitis related to continuous ambulatory peritoneal dialysis? AB - A case of peritonitis caused by Flavimonas oryzihabitans (Pseudomonas oryzihabitans; CDC group VE-2) in a patient on continuous ambulatory peritoneal dialysis is reported. This is the seventh case of infection caused by this organism reported in the English literature and the third reported case of continuous ambulatory peritoneal dialysis-related peritonitis caused by this organism; it is the first case of infection of any kind caused by this organism in England. PMID- 2913033 TI - Comparison of the virologic and immunologic responses of volunteers to live avian human influenza A H3N2 reassortant virus vaccines derived from two different avian influenza virus donors. AB - We compared the abilities of the six internal RNA segments of two avian influenza viruses, A/Mallard/Alberta/88/76 (H3N8) and A/Mallard/NY/6750/78 (H2N2), to confer attenuation on wild-type human influenza A/Bethesda/1/85 (H3N2) virus in seronegative adult volunteers. Live avian-human influenza A reassortant virus vaccines derived from either avian virus parent were comparable in the following properties: safety, infectivity, immunogenicity, and genetic stability. Since the avian influenza A/Mallard/Alberta/76 virus offered no clear advantage as a donor virus, we will conduct our future evaluations on live influenza A virus reassortants derived from the more extensively characterized avian influenza A/Mallard/NY/78 virus. PMID- 2913034 TI - Cytotoxin production by Campylobacter pylori strains isolated from patients with peptic ulcers and from patients with chronic gastritis only. AB - A total of 66.6% of Campylobacter pylori strains isolated from patients with peptic ulcers produced a cytotoxin active against mammalian cells in vitro, versus 30.1% of strains isolated from patients with chronic gastritis of various degrees of severity only. This difference was statistically significant and suggests that the toxic substance could be involved in the development of peptic ulcers. PMID- 2913036 TI - Detection of antigens in urine of mice and humans infected with Borrelia burgdorferi, etiologic agent of Lyme disease. AB - Lyme disease is a seasonal tick-borne malady which has worldwide distribution. Early and accurate diagnosis of Lyme disease is essential for successful antibiotic therapy. Symptoms are too vague to make an early diagnosis based on conventional criteria. We report the detection of antigens of Borrelia burgdorferi, causative agent of Lyme disease, in the urine of infected mice and humans. This technique may eventually provide a rapid diagnostic test for the early and accurate detection of this illness. PMID- 2913035 TI - Association of alpha interferon production with natural killer cell lysis of U937 cells infected with human immunodeficiency virus. AB - Mononuclear leukocytes from human immunodeficiency virus (HIV)-seronegative and seropositive homosexual men lysed HIV-infected U937 cells to a significantly greater degree than uninfected U937 cells. Depletion of cell subsets with monoclonal antibodies and complement indicated that the effector cells were primarily of the CD16+ phenotype. Acid-stable alpha interferon (IFN-alpha) production induced by the HIV-infected cells correlated with, although was not an absolute requisite for, preferential lysis of the infected targets. The activity of these CD16+, natural killer (NK) cells decreased in relation to the duration of HIV infection and the presence of acquired immunodeficiency syndrome. Pretreatment of peripheral blood mononuclear cells from HIV-seronegative subjects, but not HIV-seropositive men, with IFN-alpha or recombinant interleukin 2 enhanced lysis of both uninfected and HIV-infected U937 cells. These results suggest that IFN-alpha-associated, NK-like mechanisms are active in the cytotoxic response against HIV-infected cells and that HIV infection results in an early and progressive depression of such responses. Prospective investigations may be useful in determining the role of this NK cell response in the natural history and pathogenesis of HIV infection and the efficacy of therapeutic modalities. PMID- 2913037 TI - Immunoglobulin G subclass antibodies to measles virus in patients with subacute sclerosing panencephalitis or multiple sclerosis. AB - Mouse monoclonal antibodies specific for human immunoglobulin G (IgG) subclasses and a sensitive immunoassay were used to evaluate the IgG subclass antibody response to measles virus antigens in cerebrospinal fluid and serum samples from 20 patients with subacute sclerosing panencephalitis (SSPE), 12 patients with multiple sclerosis (MS), and 11 controls with high measles virus antibody titers in serum. In patients with SSPE, measles virus-specific antibodies were found mainly in the IgG1 subclass and the IgG subclass distribution remained unchanged, irrespective of the clinical stage or duration of the disease. In patients with MS and in controls, measles virus activity was also associated mainly with IgG1. However, the activity was significantly lower than that found in patients with SSPE. The results suggest that there is no primary abnormality in humoral immune response to measles virus in patients with MS. The disproportionately high levels of the measles virus-specific IgG1 subclass found in patients with SSPE may be due to persistent antigenic stimulation or reflect a defect in immunoregulatory mechanisms in response to viral infection. PMID- 2913038 TI - Human disease associated with "Campylobacter upsaliensis" (catalase-negative or weakly positive Campylobacter species) in the United States. AB - Catalase-negative or weakly positive (CNW) thermotolerant campylobacteria, first isolated from dogs in 1983, were recently recognized as a new species, "Campylobacter upsaliensis," but their association with human illness has not been established. Twelve human isolates received at the Centers for Disease Control between 1980 and 1986 were identified as CNW campylobacteria by biochemical tests, cellular fatty acid composition, and antimicrobial susceptibility patterns. Eleven CNW Campylobacter strains tested by DNA-DNA hybridization (hydroxyapatite method) were all highly related and were related to two "C. upsaliensis" strains at the species level (86% under optimal conditions and 76% under stringent conditions). Clinical information was obtained for 11 human isolates from three stool and eight blood specimens. They were isolated from four female and seven male patients 6.5 months to 83 years of age residing in 10 different states. The patients had a wide spectrum of illnesses. The stool isolates were obtained from two previously healthy persons during episodes of acute gastroenteritis and from one immunocompromised patient with persistent diarrhea and fever. The blood isolates were obtained from two infants with fever and respiratory symptoms; a young woman with a ruptured ectopic pregnancy; three elderly men with underlying chronic diseases; and two immunocompromised adults. In a bactericidal assay to assess sensitivity to serum, seven of eight blood isolates showed some resistance to killing by pooled normal human serum. These observations suggest that "C. upsaliensis" is a potential human pathogen associated with both gastroenteritis and bacteremia in normal hosts and with opportunistic infection in immunocompromised individuals. PMID- 2913039 TI - Staphylococcus intermedius in canine gingiva and canine-inflicted human wound infections: laboratory characterization of a newly recognized zoonotic pathogen. AB - Staphylococcal gingival flora was characterized in cultures from 135 dogs. Staphylococcus intermedius was isolated in 39% of the cultures, S. aureus was isolated in 10%, and both were isolated in 2.0%. S. aureus was isolated more often from dogs of working breeds with weights of greater than 40 lb (ca. 18 kg) and with outdoor habitats than was S. intermedius, which was associated with dogs of nonworking breeds with weights of less than 40 lb and indoor habitats. S. intermedius was distinguished from S. aureus by the following characteristics: coagulation of rabbit plasma at 4 h (26 versus 100%, respectively), hemolysis of sheep blood at 24 h (30 versus 79%, respectively), and mannitol fermentation at 24 h (4 versus 93%, respectively). A clear separation of the two species was apparent only with the acetoin (modified Voges-Proskauer) reaction (100% of the S. aureus isolates versus 0% of the S. intermedius isolates) and beta galactosidase activity on the API Staph-Ident strip (0% of the S. aureus isolates and 100% of the S. intermedius isolates). Susceptibilities of S. intermedius and S. aureus were 72 and 7%, respectively, to penicillin G, and 100% of both species to oxacillin. Fourteen previously collected strains of coagulase-positive staphylococci from infected canine-inflicted human wounds were reanalyzed; 3 of 14 (21%) isolates were S. intermedius. We conclude that S. intermedius is a common canine gingival flora and is responsible for some canine-inflicted human wound infections, thus representing a newly recognized zoonotic pathogen. PMID- 2913040 TI - Isolation of human immunodeficiency virus from peripheral blood lymphocytes stored in various transport media and frozen at -60 degrees C. AB - The peripheral blood lymphocytes from 48 heparinized blood specimens from human immunodeficiency virus (HIV) antibody-positive individuals were divided into two aliquots. One aliquot was reconstituted in one of the following five media. Medium 1 consisted of tryptose broth with 0.5% gelatin; medium 2 consisted of RPMI 1640 containing 10% fetal bovine serum (FBS); medium 3 consisted of RPMI 1640 containing 20% FBS, Polybrene, interleukin 2, and anti-alpha interferon; medium 4 consisted of medium 2 plus 10% dimethyl sulfoxide (DMSO); and medium 5 consisted of medium 3 plus 10% DMSO. Lymphocytes were stored in these five media at -60 degrees C. The other aliquot of cells was stored at -190 degrees C in RPMI 1640 containing 50% FBS and 10% DMSO. After 1 week, both aliquots were cocultivated with phytohemagglutinin-stimulated uninfected peripheral blood lymphocytes, and presence of HIV was detected by the reverse transcriptase test. Storage in medium 1, 2, or 3 did not result in satisfactory isolation rates, but storage at -60 degrees C in medium 4 or 5 gave equal or better isolation rates than did storage at -190 degrees C. Inactivation of HIV by freezing of the cells without DMSO correlated with high antibody titers to core and polymerase proteins as measured by Western (immuno-) blotting. PMID- 2913041 TI - Epidemiology of pharyngeal colonization of infants with aerobic gram-negative rod bacteria. AB - By using a selective medium, pharyngeal colonization with gram-negative rod (GNR) bacteria was determined in a cohort of 49 normal infants monitored from birth to 6 months of age. Culture swabs were diluted in 1 ml of saline for quantitation. The prevalence of GNR in the first 72 h of life was 8% and rose to 29% during the first month, 52% at 2.5 months, 67% at 4.5 months, and 62% at 6 to 7 months. Colonization was with substantial numbers of organisms, generally greater than 100 colonies per ml and frequently greater than 1,000 colonies per ml. The most common species were Klebsiella species, Escherichia coli, Enterobacter species, and Acinetobacter anitratus. Fewer infants who were breast fed rather than formula fed at the time of culture harbored GNR (26 versus 45%, P less than 0.05). The point prevalence of pharyngeal GNR colonization in our special care nursery was 12 of 47 (26%), which was found to be similar to that of age-matched normal infants. GNR carriage in normal infants does not appear to be a residual of organisms acquired at birth, and interpretations of GNR carriage in ill or hospitalized infants should be evaluated by comparison with these data in healthy infants. PMID- 2913042 TI - Pneumococcosuria in children. AB - Streptococcus pneumoniae was present, in pure or mixed culture, in 43 (0.08%) of 53,499 urine cultures submitted from a pediatric population over a 4-year period. Data were analyzed from 28 children, from whom 78% of these positive cultures originated. Ninety-six percent of the children were female, and the median age was 3 years (range, 0.4 to 17 years). Only five children had S. pneumoniae as the sole organism cultured from the urine, and all five had only a single urine culture. Urine from the other 23 children contained other organisms as well. Small numbers of pneumococci were found in most urines: 74% contained less than 10(4) CFU/ml and 93% contained less than 10(5) CFU/ml. There was no association between genitourinary symptoms and pneumococcosuria, and complete resolution of symptoms occurred in both treated and untreated children. Pneumococcosuria could not be explained by pneumococcal bacteremia. We conclude that pediatric pneumococcosuria is not associated with urinary tract infections in children, or with pneumococcal bacteremia or invasive disease elsewhere. Pneumococcosuria probably reflects contamination of urine specimens with S. pneumoniae from perineal colonization. PMID- 2913043 TI - Immunohistochemical studies of adult human glial cells. AB - Using immunohistochemical techniques, we examined major histocompatibility complex (MHC) antigen expression on astrocytes, oligodendrocytes, and macrophages microglia derived from surgically resected tissue from young adults and maintained in dissociated cell cultures supplemented with either fetal calf or human AB serum. The majority of these cells in culture expressed class I MHC antigens. MHC class II expression was observed on only a restricted proportion of astrocytes either under basal or induction conditions (gamma-interferon, activated lymphocyte supernatants), on the majority of macrophages-microglia under inducing conditions, and not on oligodendrocytes. MHC class II expression on astrocytes in culture did not correlate with the extent of in situ gliosis or with in vitro cell morphology. MHC antigen expression was not detected in situ immunohistochemically. These data extend observations on the dissociation of in vivo and in vitro expression of MHC antigens on glial cells. The apparent greater expression of MHC class II antigens on macrophages-microglia compared to astrocytes raises the issue of the relative roles of each of these cell types in promoting immune reactivity under pathologic conditions. PMID- 2913044 TI - Peripheral nerve lesion produces increased levels of major histocompatibility complex antigens in the central nervous system. AB - Proliferation of central nervous system (CNS) glia in response to peripheral nerve injury occurs without apparent participation of cells of the immune system. It is shown here that following transection of the rat facial nerve there is strongly elevated expression of class I, and to a lesser extent, class II antigens of the major histocompatibility complex (MHC) in the facial nucleus. It is demonstrated by double-immunofluorescence studies that the cells responsible for increased levels of MHC class I antigens are endogenous brain microglia. These findings emphasize the thought that microglia are immunocompetent cells, but, at the same time, raise the possibility for a non-immunological function of MHC antigens under conditions of neural regeneration. PMID- 2913045 TI - The adoptive transfer of chronic relapsing experimental allergic encephalomyelitis with lymph node cells sensitized to myelin proteolipid protein. AB - In this report we describe the transfer of chronic relapsing experimental allergic encephalomyelitis (EAE) with in vitro-stimulated lymph node cells (LNC) from SJL/J mice immunized with human myelin proteolipid protein (PLP). No additional immune enhancing procedures were applied in the transfer recipients. Clinical and histological EAE was transferred with 10-30 X 10(6) LNC to 27/28 mice. The LNC proliferated in vitro to PLP, but not to myelin basic protein (MBP), and induced delayed-type hypersensitivity. Enrichment for lymphoblasts by Ficoll centrifugation was essential for the disease development. The clinical course usually showed an early episode of acute paralytic illness, followed by chronic relapsing disease, and resembled the transfer of EAE using MBP-specific cells, both clinically and histologically. PMID- 2913046 TI - Differences between ocular and generalized myasthenia gravis: binding characteristics of anti-acetylcholine receptor antibody against bovine muscles. AB - We studied the binding characteristics of anti-acetylcholine receptor antibody (AChR Ab) in sera of nine patients with myasthenia gravis (MG) using affinity purified extraocular muscles (EOM) and foot muscles (FM) of bovine species. The titer of AChR Ab measured with EOM was the same as that measured with FM for both ocular and generalized MG. In patients with ocular MG, the affinity of AChR Ab, determined by Scatchard analysis, was higher for FM than for EOM (P less than 0.05), whereas it was the same for EOM and FM in those with generalized MG. On the other hand, the affinity of AChR Ab for FM was lower in generalized MG than in ocular MG (P less than 0.05), but that for EOM did not differ between the two types of MG. The affinity of AChR Ab did not change after passing the patients' sera through an EOM-affinity column. The EOM-affinity column treatment of the sera decreased the AChR Ab titer measured with EOM in all patients, but the AChR Ab titer measured with FM was decreased in only some of the patients. These data indicate that there are polyclonal or heterogeneous AChR Abs in the sera of MG patients, which does not help to explain the clinical difference between ocular and generalized MG. PMID- 2913047 TI - Hepatic oleate uptake. Electrochemical driving forces in intact rat liver. AB - Recent observations suggest that the hepatic uptake of oleate may be sodium coupled. To assess the electrochemical forces driving fatty acid uptake, we used microelectrodes to monitor continuously the electrical potential difference across the plasma membrane in the perfused rat liver while simultaneously monitoring the rate of tracer [3H]oleate uptake from 1% albumin solutions. Isosmotic cation or anion substitution was used to vary the potential difference over the physiologic range. Depolarization of cells from -29 to -19 mV by substituting gluconate for chloride reduced steady-state oleate uptake by 34%. Conversely, hyperpolarization of cells to -52 mV by substituting nitrate for chloride increased uptake by 41%. Replacement of perfusate sodium with choline depolarized the cells to -18 mV and reduced uptake by 58%, an amount greater than expected from the degree of depolarization alone. Oleate in higher concentrations (1.5 mM in 2% albumin) depolarized cells by 3 mV in the presence of sodium, but had no effect in sodium-free buffer. These results suggest that a portion of oleate uptake in the intact liver occurs by electrogenic sodium cotransport. Uptake appears to be driven by both the electrical and sodium chemical gradients across the plasma membrane. PMID- 2913048 TI - Cachectin/tumor necrosis factor-alpha formation in human decidua. Potential role of cytokines in infection-induced preterm labor. AB - This study was conducted as part of an investigation to evaluate the hypothesis that bacterial toxins (LPS or lipoteichoic acid), acting on macrophage-like uterine decidua to cause increased formation of cytokines, may be involved in the pathogenesis of infection-associated preterm labor. We found that cachectin/tumor necrosis factor-alpha (TNF-alpha) was synthesized and secreted into the culture medium by human decidual cells and explants in response to treatment with LPS. LPS treatment also caused an increase in PGF2 alpha production by decidual cells and explants. In amnion cells in monolayer culture, TNF-alpha stimulated PGE2 formation, and TNF-alpha was cytostatic (inhibited [3H]thymidine incorporation into DNA) but not cytolytic in amnion cells. TNF-alpha was not detectable (less than 0.34 ng/ml) in the amniotic fluid of normal pregnancies at midtrimester or at term before or after the onset of labor (n = 44); but TNF-alpha was present at concentrations between 2.8 and 22.3 ng/ml in amniotic fluids of 4 of 20 pregnancies with intact membranes complicated by preterm labor (less than 34 wk gestational age). LPS was present in 10 of the 20 amniotic fluids of preterm labor pregnancies, including all four in which TNF-alpha was present. Bacteria were identified in only one of the four LPS-positive, TNF-alpha-positive fluids. Cytokine formation in macrophage-like decidua may serve a fundamental role in the pathogenesis of preterm labor, including increased prostaglandin formation and premature rupture of the membranes. PMID- 2913049 TI - Developmental changes in the relation between phosphate metabolites and oxygen consumption in the sheep heart in vivo. AB - This study examines the role of phosphate metabolites in the regulation of mitochondrial oxygen consumption of the heart in vivo as a function of development. We used an open chest lamb/sheep preparation in which myocardial oxygen consumption (MVO2) was monitored via an extracorporeal shunt from the coronary sinus. Phosphate metabolites were monitored simultaneously using 31P nuclear magnetic resonance with a surface coil overlying the left ventricle. Graded infusions of epinephrine were used to increase MVO2 in both neonatal lambs (age 5-12 d, n = 8), and mature sheep (26-86 d, n = 6). The maximal increase in MVO2 achieved was 220 +/- 38% in the newborns and 350 +/- 66% in the mature animals. Associated with these increases in MVO2 in the newborn lambs are significant (P less than 0.001) decreases in PCr/ATP, and increases in calculated ADP and intracellular Pi. This was in contrast to the mature sheep, in which there were no significant changes in PCr/ATP, ADP, or Pi. In conclusion, we find that (a) there are changes in PCr/ATP, Pi, and ADP in newborn animals with moderate increases in work that are not apparent in mature animals of the same species and (b) that these changes suggest that cytosolic ATP hydrolysis products may be more important in regulation of myocardial energy metabolism in the newborn than in the adult. PMID- 2913050 TI - Cardiovascular effects of acute hypercholesterolemia in rabbits. Reversal with lovastatin treatment. AB - Hypercholesterolemia was induced in New Zealand white rabbits by feeding them a 0.5% cholesterol-enriched rabbit chow for 2 wk. Half of the cholesterol-fed rabbits were given lovastatin, a potent inhibitor of hydroxymethylglutaryl coenzyme A reductase (HMG-CoA reductase), the rate limiting enzyme in cholesterol biosynthesis, and the other half were given its vehicle (i.e., DMSO). At the end of 2 wk, the rabbits underwent experimental myocardial ischemia or a sham ischemia procedure. Ischemic animals fed the cholesterol-enriched diet for 2 wk experienced much greater cardiac damage than ischemic rabbits fed the control diet, despite the absence of any atherosclerosis. Lovastatin was shown to protect the ischemic rabbit myocardium by three different indices of ischemic damage: (a) maintenance of creatine kinase (CK) activity in the ischemic myocardium; (b) reduced loss of free amino-nitrogen containing compounds from the ischemic myocardium; and (c) blunting the rise of plasma CK activity. These effects were not due to differences in myocardial oxygen demand between the groups. Arteries isolated from animals fed the cholesterol-enriched diet developed defects in endothelium-dependent relaxation in both large vessels as well as coronary resistance vessels. Acute hypercholesterolemia increases the severity of myocardial ischemia while at the same time impairing endothelium-dependent relaxation. These deleterious changes can be significantly attenuated by treatment with lovastatin. PMID- 2913051 TI - Rearrangements and point mutations of P450c21 genes are distinguished by five restriction endonuclease haplotypes identified by a new probing strategy in 57 families with congenital adrenal hyperplasia. AB - Congenital adrenal hyperplasia (CAH) is caused by disorders of the P450c21B gene, which, with the P450c21A pseudogene, lies in the HLA locus on chromosome 6. The near identity of nucleotide sequences and endonuclease cleavage sites in these A and B loci makes genetic analysis of this disease difficult. We used a genomic DNA probe that detects the P450c21 genes (A pseudogene, 3.2 kb; B gene, 3.7 kb in Taq I digests) and the 3' flanking DNA not detected with cDNA probes (A pseudogene, 2.4 kb; B gene, 2.5 kb) to examine Southern blots of genomic DNA from 68 patients and 165 unaffected family members in 57 families with CAH. Of 116 CAH bearing chromosomes, 114 could be sorted into five easily distinguished haplotypes based on blots of DNA digested with Taq I and Bgl II. Haplotype I (76 of 116, 65.6%) was indistinguishable from normal and therefore bore very small lesions, presumably point mutations. Haplotype II (4 of 116, 3.4%) and haplotype III (8 of 116, 6.9%) had deletions and duplications of the P450c21A pseudogene but had structurally intact P450c21B genes presumably bearing point mutations; point mutation thus was the genetic defect in 88 of 116 chromosomes (75.9%). Haplotypes IV and V lack the 3.7-kb Taq I band normally associated with the P450c21B gene. Haplotype IV (13 of 116, 11.2%) retains all other bands, indicating that the P450c21B gene has undergone a gene conversion event, so that it is now also associated with a 3.2-kb band. Haplotype V (13 of 116, 11.2%) lacks the 2.4-kb Taq I fragment and the 12-kb Bgl II fragments normally associated with the P450c21A pseudogene, as well as lacking the 3.7-kb Taq I fragment, indicating deletion of approximately 30 kb of DNA, resulting in a single hybrid P450c21A/B gene. Most (114 of 116, 98%) CAH alleles thus can easily be classified with this new probing strategy, eliminating many ambiguities resulting from probing with cDNA. PMID- 2913052 TI - Quantitative assessment of canalicular bile formation in isolated hepatocyte couplets using microscopic optical planimetry. AB - Isolated rat hepatocyte couplets (IRHC) are primary units of bile secretion that accumulate fluid in an enclosed canalicular space with time in culture. We have quantitated the rate of canalicular secretion in IRHC cultured for 4-8 h by measuring the change in canalicular space volume by video-microscopic optical planimetry using high resolution Nomarski optics. Electron microscopic morphometric studies revealed significant increases in canalicular membrane area after 4-6 h in culture. Canalicular secretion in basal L-15 medium (3.8 +/- 1.3 fl/min) increased significantly with the choleretic bile salts (10 microM), taurocholate, and ursodeoxycholate (14 +/- 7 fl/min each). Secretion rates after exposure to bile acids correlated directly with the canalicular surface area before stimulation. In contrast, expansion times after stimulation varied inversely with initial canalicular volumes. Ursodeoxycholic acid failed to produce a hypercholeresis at 10-, 100-, or 200-microM concentrations compared with taurocholate, either in normal or taurine-depleted IRHC. The present findings establish that rates of canalicular bile secretion can be quantitated in IRHC by serial optical planimetry, both in the basal state and after stimulation with bile acids. Furthermore, ursodeoxycholate does not acutely induce hypercholeresis at the canalicular level in this model. Rather, both taurocholic and ursodeoxycholic acids induced secretion in proportion to the surface area of the canalicular membrane. The IRHC are a useful model to identify canalicular choleretics and for studies of canalicular bile formation. PMID- 2913053 TI - A lethal variant of osteogenesis imperfecta has a single base mutation that substitutes cysteine for glycine 904 of the alpha 1(I) chain of type I procollagen. The asymptomatic mother has an unidentified mutation producing an overmodified and unstable type I procollagen. AB - A fraction of the pro alpha 1(I) and pro alpha 2(I) chains in type I procollagen synthesized by the fibroblasts from a proband with a lethal variant of osteogenesis imperfecta were overmodified by posttranslational reactions. After digestion with pepsin, some of the alpha 1(I) chains were recovered as disulfide linked dimers. Mapping of cyanogen bromide peptides indicated that the disulfide link was contained in alpha 1-CB6, the cyanogen bromide fragment containing amino acid residues 823-1014 of the alpha 1(I) chain. Nucleotide sequencing of cDNA clones demonstrated a substitution of T for G that converted glycine 904 of the alpha 1(I) chain to cysteine. A large fraction of the type I procollagen synthesized by the proband's fibroblasts had a thermostability that was 3-4 degrees C lower than the normal type I procollagen as assayed by brief proteinase digestion. In addition, the type I procollagen synthesized by the proband's fibroblasts was secreted with an abnormal kinetic pattern in that there was a lag period of about 30 min in pulse-chase experiments. The mutation of glycine to cysteine was not found in type I procollagen synthesized by fibroblasts from the proband's parents. Therefore, the mutation was a sporadic one. However, the mother's fibroblasts synthesized a type I procollagen in which part of the pro alpha chains were overmodified and had a lower thermostability. Therefore, the proband may have inherited a mutated allele for type I procollagen from her mother that contributed to the lethal phenotype. The mother was asymptomatic. She was somewhat short and had slightly blue sclerae but no definitive signs of a connective tissue abnormality. The observations on the mother indicated, therefore, that a mutation that causes synthesis of a type I procollagen with a lowered thermal stability does not necessarily produce a heritable disorder of connective tissue. PMID- 2913055 TI - Intracellular and nuclear binding of [3H]dihydrotestosterone in cultured genital skin fibroblasts of patients with severe hypospadias. AB - Androgens stimulate the development and growth of the male external genitalia. Because hypospadias is the most common congenital defect of the male urethra and because in most cases the cause of this malformation is unknown, we examined the hypothesis that the etiology of the severe forms of this disorder, which is frequently associated with other genital anomalies, might be explained by receptor abnormalities. Intracellular and nuclear binding of androgens were determined in cultured genital skin fibroblasts from 10 males who underwent circumcision for phimosis (controls A), 2 patients with 5 alpha-reductase deficiency (controls B), and 11 patients with severe forms of hypospadias of unknown etiology. Genital skin fibroblast monolayers were incubated for 60 min at 37 degrees C with varying concentrations of [3H]-dihydrotestosterone ([3H]DHT), and specific binding in whole cells and nuclei was measured. Maximum binding (Bmax) in the whole cell assay averaged 0.88 +/- 0.15 fmol . microgram DNA-1 (mean +/- SD) in the control group (controls A, 0.89 +/- 0.16 fmol . microgram DNA-1; controls B, 0.85 fmol . microgram DNA-1) and 0.7 +/- 0.25 fmol . microgram DNA-1 in the patients with hypospadias. In the latter group, Bmax in six patients was below the minimum values determined in the controls. Maximum specific nuclear binding in the control groups averaged 43% (range, 30-55%) of the corresponding intracellular binding. In contrast, nuclear binding in strains from patients with hypospadias was lower (range, 0-12% of whole cell Bmax). In particular, no high affinity saturable nuclear [3H]DHT binding could be measured in 6 of the 11 patients. We interpret these data to suggest that defective intracellular and/or nuclear binding might be the cause of defective genital development in some patients with severe hypospadias. PMID- 2913054 TI - Differential expression of the two human arginase genes in hyperargininemia. Enzymatic, pathologic, and molecular analysis. AB - Previous studies in our laboratory and others have demonstrated in humans and other mammals two isozymes of arginase (AI and AII) that differ both electrophoretically and antigenically. AI, a cytosolic protein found predominantly in liver and red blood cells, is believed to be chiefly responsible for ureagenesis and is the one missing in hyperargininemic patients. Much less is known about AII because it is present in far smaller amounts and localized in less accessible deep tissues, primarily kidney. We now report the application of enzymatic and immunologic methods to assess the independent expression and regulation of these two gene products in normal tissue extracts, two cultured cell lines, and multiple organ samples from a hyperargininemic patient who came to autopsy after an unusually severe clinical course characterized by rapidly progressive hepatic cirrhosis. AI was totally absent (less than 0.1%) in the patient's tissues, whereas marked enhancement of AII activity (four times normal) was seen in the kidney by immunoprecipitation and biochemical inhibition studies. Immunoprecipitation-competition and Western blot analysis failed to reveal presence of even an enzymatically inactive cross-reacting AI protein, whereas Southern blot analysis showed no evidence of a substantial deletion in the AI gene. Induction studies in cell lines that similarly express only the AII isozyme indicated that its activity could be enhanced severalfold by exposure to elevated arginine levels. Our findings suggest that the same induction mechanism may well be operative in hyperargininemic patients, and that the heightened AII activity may be responsible for the persistent ureagenesis seen in this disorder. These data lend further support to the existence of two separate arginase gene loci in humans, and raise possibilities for novel therapeutic approaches based on their independent manipulation. PMID- 2913057 TI - Morphology of fungiform papillae in canine lingual epithelium: location of intercellular junctions in the epithelium. AB - The localization and structure of intercellular junctions and barriers in the extragemmal epithelium of canine fungiform papillae were determined by using both morphological and electrophysiological methods. Gap junctions were located in all epithelial strata with the exception of the stratum corneum, suggesting that the epithelium functions as a syncytium. The extracellular space of the stratum corneum was composed of a discontinuous, three-dimensional network of tight junctions, modified desmosomes, and lamellar bodies. A zonula occludens, which stops the penetration of lanthanum, is present in the uppermost layer of the stratum granulosum. In freeze-fracture replicas, tight junctions appear as extended networks of ridges of variable thickness on the PF fracture face and complementary grooves on the EF fracture face. The relatively high resistance pathway resulting from the layers of corneocytes and networks of tight junctions and lamellar bodies in the stratum corneum is bypassed by the low-resistance pathway provided by the taste pore. PMID- 2913058 TI - Zonal organization of climbing fiber projections to the uvula in the cat. AB - Climbing fiber projections from the inferior olive to the uvula of the cerebellum were studied in the cat by using retrograde axonal transport of horseradish peroxidase. Following large and small injections into various parts of the uvula, the distribution of labeled cells in the inferior olive was investigated. The findings indicate six longitudinal zones extending throughout the dorsal and ventral uvula: the caudal part of the nucleus beta projects to a most medially located zone (caudal beta zone) with a width of about 0.4 mm; the rostral part of the nucleus beta projects to a zone located at about 0.6 mm from the midline (rostral beta zone); the caudal part of the medial accessory olive (MAO) projects to a zone (caudal MAO zone) located lateral to the rostral beta zone; the dorsomedial cell column projects to a zone (dorsomedial cell column zone) located in the intermediate part of the uvula at about 1.2 mm from the lateral edge of the uvula; the ventral lamella of the principal olive (PO) projects to a zone (ventral lamella of PO zone) about 0.7 mm from the lateral edge of the uvula; finally, the rostral part of the MAO projects to the most lateral zone (rostral MAO zone). These conclusions are in general agreement with those of earlier studies and also provide a more detailed zonal configuration of climbing fiber projections to the uvula. PMID- 2913056 TI - Erythromycin breath test as an assay of glucocorticoid-inducible liver cytochromes P-450. Studies in rats and patients. AB - The major P-450IIIA gene family member present in human liver is HLp which, like its rat liver orthologue P-450p, is inducible by glucocorticoids and catalyzes erythromycin N-demethylation. To develop a practical method to estimate the amounts of HLp in patients [14C]N-methyl erythromycin was injected into rats that had been pretreated with dexamethasone or with inducers of other forms of cytochrome P-450. The rate of demethylation of this substrate, measured simply as 14CO2 in the breath, correlated well with the concentrations of immunoreactive P 450p protein (r = 0.70), holocytochrome P-450p (r = 0.70), or with erythromycin N demethylase activity (r = 0.90) determined in the liver microsomes prepared from each rat. Next, [14C]N-methyl erythromycin was administered to 30 patients and there was a sixfold interindividual variation in breath 14CO2 production seemingly unrelated to medications, smoking status or age. However, the average breath test values were twofold greater in female as compared to male patients (P less than 0.01). Breath 14CO2 production rose in patients retested after treatment with the P-450IIIA inducers dexamethasone (P less than 0.05) or rifampicin (P less than 0.05) and was decreased after treatment with the HLp inhibitor triacetyloleandomycin (P less than 0.05). We conclude that the erythromycin breath test provides a convenient assay of P-450IIIA cytochromes in rats and in some patients. PMID- 2913059 TI - Differential mossy fiber projections to the dorsal and ventral uvula in the cat. AB - The brainstem afferents to the uvula were studied by using retrograde axonal transport of horseradish peroxidase in the cat. Findings indicate differential afferent projections to the ventral and dorsal uvula. Major sources projecting to the ventral uvula include the caudal parts of the medial and inferior vestibular nuclei, the x- and f-groups of the vestibular nuclei, the dorsal and central parts of the superior vestibular nucleus, the rostral dorsomedial part of the paramedian nucleus of the pontine nuclei, the caudal part of the prepositus hypoglossal nucleus, and the infratrigeminal nucleus. Labeled cells in the vestibular nuclei were 74.7% of the total number of labeled cells in cat 40. On the other hand, the major sources projecting to the dorsal uvula are the peduncular, paramedian, and lateral nuclei of the pontine nuclei at the rostral and intermediate levels. Labeled cells in the pontine nuclei comprised 82.1% of the total number of labeled cells in cat 1. Findings also indicate that the lateral part of the ventral uvula receives input mainly from the pontine nuclei, whereas the medial part of the ventral uvula receives input mainly from the vestibular nuclei. Mediolateral differences were not found for the dorsal uvula. These mossy fiber zones are mediolaterally wide, with a dorsoventral partition in the uvula, in contrast to the climbing fiber zones, which are narrow (about 0.4 mm) and extend longitudinally throughout the uvula. There are quantitative differences in afferent sources to the ventral uvula and flocculus, both of which belong to the vestibulocerebellum. The largest afferent sources for the ventral uvula are the vestibular nerve and nuclei, whereas the largest sources for the flocculus are the reticular formation and raphe nuclei. These quantitative differences may have an important role for differential functions between the ventral uvula and flocculus. It has been suggested that the ventral uvula controls the velocity storage integrator of the vestibuloocular and optokinetic reflexes, whereas the flocculus is responsible for rapid changes of eye velocity in these reflexes. PMID- 2913060 TI - GABA-like immunoreactivity in the cat retina: light microscopy. AB - Semithin sections of the cat retina were stained with antibodies against GABA conjugated to bovine serum albumin with glutaraldehyde. Labelled cells were visualized by means of the peroxidase-antiperoxidase method. In the outer plexiform layer both A- and B-type horizontal cells and the B-type axon terminal system expressed GABA-like immunoreactivity. Approximately 25-30% of all amacrine cells and the whole inner plexiform layer were heavily labelled. Two types of putative GABA-ergic interplexiform cells could be distinguished. One of them also expressed tyrosine-hydroxylase-like immunoreactivity. A few bipolar cells were also GABA-immunolabelled. GABA-like immunoreactivity and 3H-muscimol uptake were colocalized in 90% of the amacrine cells labelled. However, horizontal cells did not accumulate 3H-muscimol. PMID- 2913061 TI - GABA-like immunoreactivity in the cat retina: electron microscopy. AB - The synaptic organization of the cat retina was studied with antibodies against the GABA-GA (glutaraldehyde)-BSA (bovine serum albumin) complex. The postembedding technique combined with immunogold labelling ensured ultrastructural preservation and made identification of synapses possible. The most common putative GABA-ergic synapses in the inner plexiform layer were amacrine-to-bipolar-cell synapses followed by amacrine-to-ganglion-cell and amacrine-to-amacrine-cell synapses. GABA-immunoreactive amacrine cells received most of their synaptic input from bipolar cells followed by other amacrine cells. Synapses between two labelled amacrine cells were common. Rod bipolar cells were the predominant input source and also the preferred output target of GABA labelled amacrine cells. OFF- and ON-ganglion cells received putative GABA-ergic synapses at their dendrites in laminas a and b, respectively, and also at their somata. In the outer plexiform layer, synapses of interplexiform cells onto bipolar cell dendrites expressed GABA-like immunoreactivity. In both the cone pedicles and the rod spherules, GABA-like immunoreactivity was observed in horizontal cell processes. PMID- 2913062 TI - Immunohistochemical distribution of serotonin in spinal autonomic nuclei: I. Fiber patterns in the adult rat. AB - The differential distribution of serotonin (5HT) fibers in spinal laminae VII and X is described for the adult rat. The results indicate that descending 5HT fibers preferentially innervate those regions of lamina VII that contain sympathetic and parasympathetic neurons. In lamina X, especially the dorsal commissural nucleus, large numbers of 5HT fibers are observed throughout the spinal cord. Moreover, sympathetic nuclei are more richly innervated with 5HT than the spinal parasympathetic nuclei. Spinal cord hemisections reveal that spinal autonomic nuclei are differentially innervated: ipsilateral serotoninergic projections to the intermediolateral cell column are preferentially interrupted. In addition, a large crossed 5HT projection exists throughout the length of the spinal cord that decussates five to six spinal segments rostral to its termination. Both crossed and uncrossed 5HT fibers span many spinal segments and have large numbers of collaterals. Spinal cord transections show that the vast majority of spinal 5HT descends from the brainstem but that some 5HT fibers are of intrinsic origin. PMID- 2913063 TI - Immunohistochemical distribution of serotonin in spinal autonomic nuclei: II. Early and late postnatal ontogeny in the rat. AB - These studies reveal that the postnatal ontogeny of serotonin (5HT) in the sympathetic nuclei of the rat spinal cord is protracted; the adult complement of 5HT-immunoreactive fibers is not achieved until at least 60 days of age. As descending serotonin fibers innervate and demarcate the distribution of preganglionic sympathetic nuclei, rostral-caudal and temporal gradients exist. Additionally, a heterogeneous segmental 5HT ontogenetic pattern is observed in sympathetic nuclei. Most serotonin fibers in laminae VII and X are unorganized at birth except for some sympathetic nuclei in high thoracic regions where the 5HT sympathetic pattern is being initiated. By postnatal day 6 the framework of the 5HT pattern is established in all sympathetic nuclei, and by postnatal day 16 a pattern is formed, which develops into the compact adult state by postnatal day 60. The protracted period of sympathetic 5HT development corresponds with the length of time it takes for the autonomic nervous system to mature. In addition, 5HT intraspinal cell bodies are observed at all time points examined, except for the day of birth, and are found in the same regions as adult 5HT neurons, i.e., dorsal or lateral to the central canal in laminae VII and X and in all spinal segments except cervical levels. Many of the 5HT neurons are pericanalicular and bipolar in appearance. Multipolar 5HT neurons are first observed on postnatal day 45. PMID- 2913064 TI - Intrinsic connections of rat primary visual cortex: laminar organization of axonal projections. AB - The organization of local projections within the rat primary visual cortex (area 17) was investigated by tracing fibers with HRP in in vitro brain slices. The projections from different layers showed distinct laminar patterns. Layer 4 made a strong, topographically precise, projection to lower layer 2/3; weaker projections extended laterally and terminated diffusely in layer 2/3 but also ran vertically to layers 5 and 6. The connections of lower and upper layer 2/3 were reciprocal and point-to-point. Within layer 2/3, a large number of fibers ran horizontally and terminated at variable distances from the injection site without making terminal clusters. The main output from layer 2/3 was to layer 5. The most prominent projections from the upper half of layer 5 were to layers 2/3 and 6; lower layer 5, in contrast, made wide-ranging, clustered projections to layer 1, the bottom of layer 2/3, and the top of layers 4 and 5. The patches were 130-160 micron wide and spaced apart by 230-260 micron. The main projection that arose from the superficial layer 6 terminated in layer 4 above the injection site. In contrast, lower layer 6 made clustered projections to the layer 3/4 border, extending up to 2 mm in the coronal plane. The patches were 190-220 micron wide and spaced apart by 320-390 micron. Additional projections went to the layer 5/6 border and layers 1 and 2. These results indicate that geniculocortical input is processed through interlaminar connections that are topographically precise, widespread, or patchy. These connectivity patterns suggest a role for these connections in the transformation of functional maps between layers; focused projections preserve the architecture of the layers of origin, and diverging or patchy projections rearrange this organization and form new maps in the target layers (Lund: Annu. Rev. Neurosci. 11:253-288, '88). However, only a few interlaminar connections show one of these patterns in isolation, making it difficult to assign a single function to a particular connection. We, therefore, tentatively conclude that projections terminating in layers 1-4, with the possible exception of the connection between upper layer 6 and layer 4, transform functional maps. In contrast, the topographically precise projections from upper to lower layers preserve functional maps. The specific role of these connections in the construction of receptive field properties, however, is not known.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2913065 TI - Prevention of optic nerve regeneration in the frog Hyla moorei transiently delays the death of some ganglion cells. AB - We have previously reported that a proportion of ganglion cells die during optic nerve regeneration in the adult frog Hyla moorei (Humphrey and Beazley, '85). Here we assess the effect of preventing optic nerve regeneration on this cell loss. The optic nerve was crushed unilaterally and regeneration was allowed to progress unimpeded in one experimental series but was prevented by ligating or capping the nerve in another. We estimated total cell numbers in the ganglion cell layer from cresyl-stained wholemounts, comparing each experimental retina with its unoperated partner. At 70-78 days postcrush, mean cell numbers had fallen by 31.5% for frogs with unimpeded regeneration (N = 9), a significantly greater reduction than the 21.5% (N = 8) loss for the impeded regeneration series (p less than 0.001). Thereafter, cell numbers were stable for frogs with unimpeded regeneration. Cell death continued in the series with impeded regeneration, and losses exceeded those of frogs with unimpeded regeneration from 110 days postcrush. When regeneration was impeded, ganglion cell somas underwent an intense cell soma reaction and became arranged in rows radiating from the optic nerve head. Our findings indicate that some ganglion cells are transiently spared when regeneration of their axons is prevented. The abnormally extensive contacts formed between somas may delay ganglion cell loss. However, the eventual death of most ganglion cells shows them to be target-independent in the long term. PMID- 2913066 TI - Central projections of the rat radial nerve investigated with transganglionic degeneration and transganglionic transport of horseradish peroxidase. AB - Transganglionic degeneration and transganglionic transport of HRP were used for investigation of the spinal cord and brainstem projections from the superficial, cutaneous (SR) and deep, muscular (DR) branches of the radial nerve. The HRP study included a numerical and size analysis of labelled dorsal root ganglion (DRG) cells. In degeneration experiments the SR nerve was found to project somatotopically to laminae III-IV, but degeneration was also found in lamina I and inconsistently in lamina II. Transection of the DR nerve was found to give rise to a small amount of degeneration, which in "sham" operations was established to result from the skin injury during dissection of the DR nerve. With the HRP method, the SR nerve was found to project somatotopically to laminae I-IV, whereas the DR nerve projected more diffusely to the medial part of laminae V-VII. HRP application to the SR and DR nerves resulted in labelling of a mean of 1,024 and 310 DRG cells, respectively. These labelled neurons had a median cell area of 381 and 562 micron 2 for the SR and DR nerves, respectively, and both small and large cells were labelled in both types of experiments. In the lower brainstem, projections from the SR nerve were found only in the ipsilateral dorsal part of the main cuneate nucleus (MCN) with both methods. Brainstem projections from the DR nerve that were found only with the HRP method were found in the ipsilateral ventral part of the MCN together with a projection to the ipsilateral external cuneate nucleus. No projections were found to the central cervical nucleus. The present results indicate that cutaneous compared to muscular primary sensory neurons are much more prone to react with transganglionic degeneration after peripheral nerve transection. Furthermore, in the rat the SR nerve projects somatotopically, whereas the DR nerve does not. Both nerve branches are connected to small and large spinal ganglion cells, although the median cell area is larger in muscular neurons. PMID- 2913067 TI - Number of neurons in individual laminae of areas 3B, 4 gamma, and 6a alpha of the cat cerebral cortex: a comparison with major visual areas. AB - The number of neurons per mm3 of tissue (number per volume) and the number under 1 mm2 of cortical surface (number per column) have been estimated for each lamina of seven cytoarchitectural areas of the cat cortex by using a method of size frequency distribution. The areas studied consisted of four visual areas (the binocular and monocular portions of area 17: 17B and 17M; area 18; and the posteromedial lateral suprasylvian area: PMLS), a somatosensory area (3B), and two motor areas (4 gamma and 6a alpha). For both series of measurements, significant differences could be demonstrated among the seven areas studied (one way ANOVA; P less than .001). The number of neurons per volume in the binocular and monocular regions of area 17 (approximately 49,000/mm3) is 85% greater than that of each of the other regions (approximately 27,000) with a P less than .01 on an a posteriori Tukey test, but there are no significant differences between the latter areas. The number of neurons per column is greater in the binocular portion of area 17 (78,000 under 1 mm2 of cortical surface) than in any other area (P less than .01). Other sensory areas (17M, 18, PMLS, and 3B) have fewer neurons per column (P less than .01) and the numbers do not vary significantly between these regions (range from 56,100 to 61,900). Areas 4 gamma and 6a alpha have still fewer neurons (approximately 44,000; P less than .01, except P less than .05 when compared to PMLS). Thus, the seven areas studied fall under three different categories. Motor areas have the smallest number of neurons per column, sensory areas have more, and the greatest number is found in the binocular region of area 17. It appears that these differences are principally (but not exclusively) due to variations in the number of neurons in layer IV: These variations are largely responsible for the differences that we have found between the binocular portion of area 17 and other sensory areas as well as between the latter and motor areas. We thus cannot confirm the view of Rockel et al. (Brain 103:221-244, '80) that there is a basic uniformity of the number of neurons per unit of cortical surface in different cortical areas of the cat. PMID- 2913068 TI - Collateralization of the amygdaloid projections of the rat prelimbic and infralimbic cortices. AB - Previous studies indicate that the distribution of corticoamygdaloid neurons in the rat prelimbic (PL) and infralimbic (IL) cortices overlaps with the distribution of neurons projecting to the contralateral medial prefrontal cortex (MPC), insular cortex, mediodorsal thalamus, and dorsal medulla. In view of the poorly differentiated cytoarchitecture of PL and IL, and their designation as cortical regions transitional between the allocortex and isocortex, the present study sought to determine whether several cortical and subcortical projections from these areas arise as collaterals of corticoamygdaloid neurons. Injections of the fluorescent dyes Fast Blue (FB) or bisbenzimide (BB) were made into the amygdaloid complex and the following areas: agranular and granular insular cortices; mediodorsal thalamic nucleus (MD); nucleus tractus solitarii/dorsal medulla (NTS); contralateral amygdaloid complex; and ipsilateral and contralateral MPC. Neurons projecting to the ipsilateral amygdaloid complex were located mainly in layers II and V with fewer cells in layer III. Concomitant injections into the insular cortex, MD, and NTS labeled populations of neurons arranged in laminae that partially overlapped with, but were essentially separate from, corticoamygdaloid neurons. Projections to the insular cortex arose from layers II and V; those to MD arose from layers V and VI. Corticobulbar projections from IL originated from neurons arranged in a thin lamina in the deep part of layer V. Very few neurons projecting to both the amygdaloid complex and any of these areas were observed. Bilateral injections of FB and BB into the amygdaloid complex producted very few double-labeled cells in PL and IL. Further, in layer V, ipsilaterally projecting corticoamygdaloid neurons tended to be located more deeply than contralaterally projecting neurons. Combined injections of BB and FB into the amygdaloid complex and the contralateral (but not ipsilateral) MPC resulted in significant numbers of double-labeled neurons in layers II, III, and V of PL and IL. Control injections of fluorescent dyes into the cerebrospinal fluid labeled few neurons in the superficial layers of PL and IL and a combined injection into the amygdaloid complex (FB) and subarachnoid space (BB) resulted in a very small number of double-labeled cells in layer II only. The results suggest that a significant proportion of neurons in PL and IL projecting to the amygdaloid complex issue collaterals innervating the contralateral MPC. Evidence is discussed that suggests that the interhemispheric collaterals of MPC corticoamygdaloid neurons may serve to correlate the amygdaloid outputs of the MPC bilaterally. PMID- 2913069 TI - Morphological study of flight motor neurons in the cricket. AB - The motor innervation of the major flight muscles powering the fore- and hindwings of the cricket Teleogryllus oceanicus was investigated. The morphology of the motor neurons was determined by filling them via their axons in the periphery with either Lucifer Yellow or cobalt chloride followed by silver intensification. Details of the location of branches of motor neurons within the ganglion were obtained by serially sectioning ganglia containing filled neurons. For each flight muscle at least two motor neurons were found. The somata of motor neurons were located in two clusters in the ganglion, the anterior lateral cluster and the posterior lateral cluster. Motor neurons in the same cluster had similar morphologies. Most of the arborizations of these motor neurons were in the dorsal neuropil with a few branches in the lateral intermediate neuropil. The morphology of flight motor neurons was compared with the morphology of leg motor neurons in consideration of the possible functional organization of the ganglion. A comparison was made between motor neurons innervating homologous muscles of the cricket and the locust to determine the extent of the difference between the flight systems of these two groups. PMID- 2913070 TI - Distribution of reduced-nicotinamide-adenine-dinucleotide-phosphate diaphorase positive cells and fibers in the cat central nervous system. AB - Previous histochemical studies have suggested that reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase exists in distinct subsets of neurons that neither belong to a single transmitter type nor embrace all the neurons using a single transmitter. As a step toward establishing the role of this enzyme, the distribution of NADPH-diaphorase-positive neurons and fibers in the cat central nervous system was mapped by using a direct histochemical method. Heavily stained NADPH-diaphorase-positive neurons with many prominent cell processes were observed in the cerebral cortex, white matter, caudate nucleus, putamen, nucleus accumbens, septal nucleus, amygdala, anterior, lateral and posterior hypothalamic areas, dorsolateral part of the periaqueductal gray, superior colliculus, central tegmental field (Berman) (pedunculopontine tegmental area), dorsal tegmental nucleus, nucleus coeruleus, mesencephalic and pontine reticular formation, gigantocellular and magnocellular tegmental fields, nucleus facialis, and motor nucleus of the vagus. Moderately stained neurons with two or three prominent cell processes were observed in the nucleus of the diagonal band of Broca, globus pallidus, and substantia innominata. Medium-size, moderately stained neurons that had round large nuclei and no visible cell processes were found in the subthalamic nucleus, pontine gray, trapezoid body, and infratrigeminal, cochlear, and vestibular nuclei. Very dense NADPH-diaphorase positive nerve terminal fields were seen in the olfactory tubercle, cortex, caudate nucleus, putamen, dentate gyrus, and interpeduncular nucleus. Intensely stained NADPH-diaphorase-positive nerve fibers were found in the stria terminalis, marginal region of the central tegmental field, dorsal tegmental nucleus, and spinal trigeminal tract as well as around the brachium conjunctivum. Although the staining of neurons and tracts was highly selective, they did not correspond to any single known neuronal or neurotransmitter type. Positive staining occurred in discrete subsets of neurons known to be associated with a variety of peptides and classical neurotransmitters. The functional significance of high NADPH diaphorase activity is unknown. PMID- 2913071 TI - Morphological types of spinomesencephalic neurons in the marginal zone (lamina I) of the rat spinal cord, as shown after retrograde labelling with cholera toxin subunit B. AB - Retrogradely labelled lamina I neurons were studied after intramesencephalic injections of subunit B of cholera toxin. The tracer was visualized with a mixture of two monoclonal antibodies followed by the peroxidase-antiperoxidase technique that produced Golgi-like staining of the labelled cells. A morphological and morphometric analysis in the three anatomical viewing planes disclosed two structural neuronal types which were recognized as the fusiform and pyramidal cells of our Golgi-based classification of rat marginal cells. Fusiform cells had a bipolar longitudinally elongated dendritic arbor, were located in the lateral third of lamina I, and appeared to project mainly to the contralateral parabrachial nuclei. It is asserted that these cells may convey the spinal input which elicits visceral responses generated in that area. Pyramidal cells were longitudinally oriented pyramids with the triangular base straddling the dorsal horn/white matter border and a dendritic arbor extending lateromedially and mainly rostrocaudally throughout superficial lamina I and the dorsal funiculus. These cells occurred along the entire mediolateral extent of lamina I and seemed to have a prevalent projection to the contralateral caudal ventrolateral periaqueductal gray. They may represent the ascending branch of the spinal midbrain loop centered in that zone which controls nociceptive transmission postsynaptically in the dorsal horn. PMID- 2913072 TI - In situ malignant melanoma arising in a speckled lentiginous nevus. PMID- 2913073 TI - Possible significance of aqueous emulsified vitamin A in effective therapy for pityriasis rubra pilaris. PMID- 2913074 TI - Relapsing polychondritis associated with psoriasis vulgaris. PMID- 2913075 TI - Diagnosis and treatment of impetigo. PMID- 2913076 TI - Bald scalps and wrinkles. PMID- 2913077 TI - Chemotaxis in psoriasis. PMID- 2913078 TI - Rust remover rash. PMID- 2913079 TI - Human immunodeficiency virus infection and porphyria cutanea tarda. AB - A recent report documents three homosexual men with porphyria cutanea tarda associated with acquired immune deficiency syndrome (AIDS). We report two brothers with hemophilia and human immunodeficiency virus (HIV) exposure who developed porphyria cutanea tarda. These brothers are heterosexual, have familial porphyria cutanea tarda, and developed overt familial porphyria cutanea tarda in their early twenties. One brother's symptoms were provoked by attending an ultraviolet A suntanning parlor. Our two patients, unlike the previously reported three patients, have not developed AIDS, though one patient has evidence of defective cell-mediated immunity. Three of the five cases of porphyria cutanea tarda associated with HIV infection involved familial porphyria cutanea tarda. It now may be advisable to order HIV serology tests in patients who have porphyria cutanea tarda. We recommend that HIV-positive individuals avoid ultraviolet A radiation because of its immunosuppressive effects in persons already at risk of immunosuppression. Such exposure is further contraindicated in those individuals with porphyria cutanea tarda. PMID- 2913080 TI - Generalized granuloma annulare: clinical and laboratory findings in 100 patients. AB - Clinical and laboratory records of 100 biopsy-proved cases of generalized granuloma annulare seen at the Mayo Clinic between 1966 and 1986 were reviewed. The skin eruption involved predominantly annular lesions in 67 patients and predominantly nonannular papules in 33. The ratio of female-to-male patients was 2.9:1 in the annular group and 1.4:1 in the nonannular group. The mean age at onset was 51.7 years. The eruption was symptomatic in 34 patients, and specific precipitating factors could be implicated in 16 patients. No consistently associated systemic disorders were identified. Diabetes mellitus was diagnosed in 21% of our referral group of generalized granuloma annulare cases, compared with 9.7% in 1350 cases of localized granuloma annulare and 10.3% in 1383 cases of all forms of granuloma annulare seen at the Mayo Clinic in the same period. Serum lipid abnormalities were more common in the generalized annular group. Follow-up data indicated a chronic, relapsing course in most patients. PMID- 2913081 TI - Feelings of stigmatization in patients with psoriasis. AB - The concept of stigma, defined as a discrediting mark that sets a person off from others, is used in a systematic, in-depth examination of how 100 adults with psoriasis experience their illness. Information on demographic and illness variables that might predict feelings of being stigmatized were obtained. Through factor analysis of a specially designed questionnaire, six dimensions of the stigma experience were identified: anticipation of rejection, feeling of being flawed, sensitivity to others' attitudes, guilt and shame, secretiveness, and positive attitudes. There was marked variability in the presence and magnitude of these feelings. Different predictors emerged for different dimensions of the stigma experience, the most frequent being age at onset, extent of bleeding, employment status, duration, and rejection experience. Of all the aspects of the illness, bleeding proved the strongest predictor of stigma feelings and of despair, which correlates highly with stigma. Despair and feeling stigmatized may lead to noncompliance with treatment, possibly worsening the status of the psoriasis. PMID- 2913082 TI - Treatment of neoplastic skin lesions with intralesional interferon. AB - Nineteen patients with skin neoplasms were treated with intralesional recombinant interferon-alpha 2. There were 11 basal cell carcinomas, 3 squamous cell carcinomas, 4 solar keratoses, and 1 keratoacanthoma. Biopsy specimens were taken before and 2 months after treatment in most cases. Lesions were injected three times weekly for 3 weeks (nine total injections) with 0.9 X 10(6) IU (0.3 ml) of interferon-alpha 2 (total dose 8.1 X 10(6) IU). Clinical and histologic examination revealed three squamous cell carcinomas that had cleared. No basal cell carcinomas had resolved but the keratoses were clinically clear and histologically less active. One keratoacanthoma resolved. PMID- 2913083 TI - Antipsoriatic effects of zidovudine in human immunodeficiency virus-associated psoriasis. AB - Four patients with psoriasis complicating human immunodeficiency virus (HIV) infection showed marked improvement in their psoriasis after being treated with oral zidovudine. The antipsoriatic effect persisted in two patients in spite of worsening helper T cell depletion. The antipsoriatic effect appeared to be dose dependent and was associated with the development of erythrocyte macrocytosis, a known side effect of zidovudine. Zidovudine is useful for the therapy of HIV associated psoriasis and should be tested for efficacy in non-HIV-associated psoriasis. PMID- 2913084 TI - A retrospective study of bone changes in adults treated with etretinate. AB - Ninety patients aged 17 to 80 years were treated with etretinate for disorders of keratinization and were studied for bone changes. The treatment lasted from 0.1 to 7.9 years, mean 2.4 years. The average dosage of etretinate was 0.57 mg/kg/day (range 0.21 to 1.32 mg/kg/day), and the total dose was 31 gm (range 1 to 197 gm). Standard radiographs of the axial and peripheral skeleton were evaluated. The films of 44 patients showed skeletal abnormalities such as periosteal thickening, hyperostosis of the vertebral column, disk degeneration, osteoporosis, calcification of the spinal ligaments, and slender long bones. The present data indicate that the risk of skeletal disorders in adults treated with etretinate is significant (44 of 90), but that the severity of changes is minor. PMID- 2913085 TI - Solitude: nurtured in infancy; enjoyed in adulthood. PMID- 2913086 TI - Orofacial trauma and mouth-protector wear among high school varsity basketball players. AB - This investigation surveyed the prevalence and types of orofacial injuries among 1020 Florida high school basketball players during one season; it also examined the prevalence and types of mouth protectors used and their influence on sustained injuries. The results demonstrated a relatively high prevalence of players (31 percent) reporting orofacial trauma suffered during the organized playing of basketball. Most players reporting orofacial trauma indicated they received multiple injuries during the season. Only a small percentage (4.2 percent) of the basketball players surveyed reported use of mouth protectors and this use was exclusively voluntary. Those players not wearing mouth protectors reported an approximately seven-fold increase in orofacial injuries; most involved trauma to the soft tissue. Many objections were cited to the use of mouth protectors by the players, which must be overcome if compliance with future mandatory wear is recommended. Results of this survey suggest that further investigation into orofacial injuries among basketball players should be pursued. PMID- 2913087 TI - Assessment of the clinical validity of a simple scale for rating children's dental anxiety. AB - This study was carried out to assess the Simple Scale's (using a 100-mm horizontal line between the poles of 'Low Anxiety--High Anxiety') clinical validity with an instrument of known reliability and validity (namely Spielberger's STAIC), with a Child's Dental Anxiety Scale, and with responses to a short Fear Statement questionnaire. By scoring episodes of 36 children undergoing dental treatment and then obtaining their self-reports, the Simple Scale was found to correlate significantly with the A-State score from the STAIC. Other significant correlations were found. PMID- 2913088 TI - The Surgeon General's report on nutrition and health. AB - The most important accomplishment of the Surgeon General's Report is its establishment of a sound scientific basis for dietary recommendations for chronic disease prevention. From this foundation, all levels of government, the food industry and the nutrition profession should be able to develop programs and policies that put dietary recommendations into common practice. PMID- 2913089 TI - National nutrition objectives for the years 1990 and 2000. AB - Development of nutrition objectives for the years 1990 and 2000 forms an important part of a national strategy to reduce preventable health risks. These initiatives present an opportunity for nutrition professionals to define priorities for nutrition in preventive health care and to establish the nation's nutrition policy agenda for the next decade. PMID- 2913090 TI - Gemination, fusion and supernumerary tooth in the primary dentition: report of case. PMID- 2913091 TI - Central hemangioma of the mandible: report of case. PMID- 2913092 TI - Intrabony tooth injuries: reports of two cases. PMID- 2913093 TI - Traumatic implantation of a toothbrush: an unusual hazard of oral hygiene. AB - Implantation of foreign bodies into the oral soft tissues is an accident that occurs with some frequency, particularly in young children, for whom the mouth is an important sensory organ. The offending object is usually sharp; pencils are the most commonly reported object. A case is presented of a child who fell, implanting a toothbrush into her buccal soft tissues. The problems incurred in removing such an object are presented. This case demonstrates the need for parental vigilance while children are performing oral hygiene procedures. PMID- 2913095 TI - Quality assurance for 21 years. PMID- 2913094 TI - Performance time and gloves. PMID- 2913096 TI - TMJ testing. PMID- 2913097 TI - Recommendations in radiographic practices: an update, 1988. Council on Dental Materials, Instruments, and Equipment. PMID- 2913098 TI - Long-term status of TMJ clicking. PMID- 2913099 TI - Helping patients quit. PMID- 2913100 TI - Tobacco use and oral health. PMID- 2913101 TI - Dentists as smoking cessation counselors. AB - Dentists can help people quit smoking because they are experts in oral health, are accustomed to counseling about oral preventive health, and have broad exposure to the general populace. To determine dentists' counseling practices with regard to smoking cessation, a randomly selected sample of 82 dentists practicing in the San Francisco Bay Area were surveyed. Also 106 internists in the same region were surveyed. Whereas the dentists believed smoking is dangerous to health and considered counseling as an important part of their practice, only 17%, compared with 58% of the internists, frequently discussed quitting with their patients who smoke. The two groups also differed in the types of counseling they used. Dentists attributed their lack of counseling to poor insurance coverage, insufficient time, lack of training, and fear that patients might leave their practices if urged to quit. These issues must be addressed if dentists are to participate fully in helping their patients quit smoking. PMID- 2913102 TI - A statewide survey of dentists' smoking cessation advice. AB - The general practitioners of the Vermont State Dental Society (251) were surveyed in 1986 to determine their smoking cessation activities. Seventy-eight percent of the dentists completed the survey and 87% reported that they discussed concerns about smoking with their patients who smoke. They estimated spending an average of 2.4 minutes addressing cigarette smoking issues. Among those dentists who discussed smoking issues, the majority (60%) provided some advice on ways to change smoking behavior. The remaining 40% provided no guidance regarding smoking behavior change. The larger the proportion of smokers advised about smoking, the greater the dentists' interest in using incentives to help smokers make an attempt to quit. PMID- 2913103 TI - Helping smokers quit: a randomized controlled trial with private practice dentists. AB - Fifty private practitioners and their office staff members were randomly assigned to one of four groups: participants received a protocol for smoking management and a lecture on the consequences and management of smoking, or in addition, had nicotine gum freely available to patients, had stickers attached to their charts, or had gum and reminders. The percentage of patients in each group who had quit smoking a year later was 7.7, 16.3, 8.6, and 16.9, respectively, indicating a significant main effect for the gum conditions. The availability of nicotine gum also significantly increased the amount of time that patients reported they received smoking cessation counseling from the dentists and office staff. PMID- 2913104 TI - Stop-smoking program using nicotine reduction therapy and behavior modification for heavy smokers. AB - One hundred eighteen volunteers were studied in a hospital-based smoking cessation program in which nicotine polacrilex (Nicorette) was used as an adjunct to behavioral modification (group support). The "success" rate of 40% to 47% at 1 year was chemically verified. The regimen for using the nicotine polacrilex was "within labeling" but decidedly different from the regimen used in most smoking cessation programs involving this product. PMID- 2913105 TI - A peripheral giant-cell granuloma manifestation of primary hyperparathyroidism: report of case. AB - Profuse granulomatous masses of the gingiva frequently occur in patients with gingival and periodontal disease. A 33-year-old female was seen for followup of a previously treated peripheral giant-cell granuloma. Two years earlier, a mass had been removed from the gingiva between the maxillary right central and lateral incisors. Current laboratory test results indicated hyperparathyroidism, and led to the discovery of a parathyroid adenoma. After the gingival lesion, adjacent teeth, and parathyroid adenoma were removed, the patient had no further recurrence of the lesion or signs of hyperparathyroidism. PMID- 2913106 TI - The fourth season. PMID- 2913107 TI - Ethics and esthetics. PMID- 2913108 TI - Slowly enlarging, asymptomatic mass in the upper lip. AB - A case of monomorphic adenoma, basal cell variant, is described. The clinician should be aware of this tumor and its histological differential diagnosis so that patients may be treated appropriately. PMID- 2913109 TI - Left ventricular shape, afterload and survival in idiopathic dilated cardiomyopathy. AB - Because idiopathic dilated cardiomyopathy is characterized by elevated wall stress and a more spherical left ventricle, the relations among shape, afterload and survival were examined. Thirty-six patients with cardiomyopathy were prospectively studied by two-dimensional echocardiography. Data included echocardiographic short- and long-axis cavity dimensions, their ratio and, with cuff systolic blood pressure, meridional and circumferential end-systolic stress and their ratios. Survivors (n = 16) were followed up for 52 months (range 40 to 76); nonsurvivors (n = 20) died an average of 11 months after study. Survivors had a smaller left ventricular end-diastolic short-axis dimension (6.4 versus 7.1 cm, p less than 0.03) but a similar long-axis length (8.6 versus 8.3 cm). However, overall cavity shape or the ratio of short- to long-axis end-diastolic dimensions was more spherical in those with poorer survival (ratio 0.76 versus 0.68, p less than 0.02). Meridional and circumferential end-systolic stresses were similar in the two groups, but stress was more evenly distributed in the long- and short-axis planes in nonsurvivors (meridional/circumferential stress ratio 0.57 versus 0.52 in survivors, p less than 0.05). Improved survival was associated with an end-diastolic short-axis dimension less than 7.63 cm, a short- to long-axis ratio less than 0.76 and a meridional to circumferential stress ratio less than 0.54. Life table analysis revealed a 28% mortality rate in patients with all three of these characteristics compared with 100% in patients with none. Survivors and nonsurvivors did not differ in systolic cavity dimension, wall thickness, relative wall thickness, cavity volume, percent posterior wall thickening or fractional shortening.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2913110 TI - Left ventricular diastolic function: comparison of pulsed Doppler echocardiographic and hemodynamic indexes in subjects with and without coronary artery disease. AB - To evaluate the influence of left ventricular chamber stiffness and relaxation on Doppler echocardiographic indexes of diastolic function, 35 patients (mean age 60 +/- 12 years) were examined; 24 had coronary artery disease and 11 (Group I) had no cardiovascular disease. Micromanometer left ventricular pressure was recorded simultaneously with Doppler echocardiograms of mitral valve inflow and M-mode echocardiograms of left ventricular diameter. The chamber stiffness constant (k) was derived from the pressure-diameter relation. Relaxation was assessed by the isovolumic relaxation time constant (tau) derived from the exponential left ventricular pressure decay. The patients with coronary artery disease were classified into two groups on the basis of complete (Group II; n = 10) and incomplete (Group III; n = 14) relaxation. In Group I (no coronary disease), significant correlations were demonstrated between the chamber stiffness constant and the peak early filling velocity (r = 0.73; p less than 0.02), peak early to atrial filling velocity ratio (r = 0.82; p less than 0.005), atrial time-velocity integral (r = -0.73; p less than 0.02), early to atrial time-velocity integral ratio (r = 0.70; p less than 0.05), percent atrial contribution to filling (r = 0.64; p less than 0.05) and one-half filling fraction (r = 0.73; p less than 0.02). In Group II (coronary disease with complete relaxation), the chamber stiffness constant correlated with peak early filling velocity (r = 0.68; p less than 0.05), early filling time-velocity integral (r = 0.65; p less than 0.05) and early to atrial time-velocity integral ratio (r = 0.74; p less than 0.02). No correlations between k and Doppler indexes were found in Group III (coronary disease with incomplete relaxation). However, Group III demonstrated significant correlations between tau and the peak early filling velocity (r = -0.71; p less than 0.005), percent atrial contribution to filling (r = 0.56; p less than 0.05) and mean acceleration rate of early filling (r = -0.79; p less than 0.002). Thus, in subjects with normal relaxation, increasing chamber stiffness was associated with an enhanced peak early filling velocity and volume and decreased filling during atrial systole. This finding differs strikingly from the proposed influence of chamber stiffness on diastolic filling postulated by several researchers.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2913111 TI - Left ventricular diastolic dysfunction: early diastolic relaxation and late diastolic compliance. PMID- 2913112 TI - Determination of cardiac output in critically ill patients by dual beam Doppler echocardiography. AB - Recent technology in Doppler echocardiography has produced a dual beam Doppler instrument that is capable of insonating the total cross-sectional area of the ascending aorta. The purpose of this study was to evaluate the accuracy of this instrument in measuring cardiac output in critically ill patients by comparing results with those of the thermodilution-derived cardiac output. A technically adequate Doppler cardiac output measurement was attained in 71 (91%) of 78 patients. The range of thermodilution-derived cardiac output measurements was from 1.58 to 11.70 liters/min. To maximize thermodilution cardiac output reliability, several measurements were made for each patient. Those patients in whom the difference between the highest and lowest measurement varied by less than 10% from the averaged results were accepted into the 50 patient study. There was significant correlation between dual beam Doppler- and thermodilution-derived cardiac output (r = 0.96, SEE = 0.55 liters/min, p less than 0.0001). This study demonstrates that dual beam Doppler ultrasound is a promising noninvasive method of measuring cardiac output in the critically ill patient. PMID- 2913113 TI - Assessment of right ventricular anatomy and function by quantitative radionuclide ventriculography. AB - Determination of right ventricular ejection fraction and volumes from radionuclide studies is cumbersome and is subject to considerable methodologic error. Further, assessment of regional wall motion has only infrequently been approached in a systematic way. A system of right ventricular ejection fraction and volume measurements is described that utilizes the previously validated single plane geometric method applied to first pass radionuclide angiocardiograms. Five right ventricular chords were defined and used to assess regional wall motion; normal values were obtained from 14 patients who were without demonstrable cardiac disease. Among 23 patients with anterior myocardial infarction, the right ventricular ejection fraction was within 2 SD of normal in 16; however, 3 of these patients showed regional wall motion abnormalities in the right ventricle. Of 21 patients with inferior myocardial infarction, right ventricular ejection fraction was reduced in 15; of the 6 with normal values, 3 had regional wall motion abnormalities as demonstrated by the chord shortening method. Of 21 patients with dilated cardiomyopathy, right ventricular function was abnormal in 20; the presence of a wall motion abnormality in the conus segment separated these patients from patients with right ventricular dysfunction after recent myocardial infarction. Thus: 1) right ventricular ejection fraction, volumes and wall motion can be assessed by a simple, geometric technique; 2) analysis of chord shortening by this method provides information unavailable from global ejection fraction data alone; and 3) the clinical correlates of these data will require further investigation. PMID- 2913114 TI - Right ventricular performance assays: slowly coming of age. PMID- 2913115 TI - Fractionated endocardial electrograms are associated with slow conduction in humans: evidence from pace-mapping. AB - Fractionated ventricular electrograms recorded during catheter mapping may arise from areas of asynchronous depolarization associated with slow conduction, the substrate for reentrant ventricular tachycardia, but can also be a nonspecific abnormality or even artifact. To determine whether fractionated sinus rhythm electrograms are associated with slow conduction in humans, the results of endocardial catheter mapping and pacing at 133 endocardial sites in 13 patients were analyzed. Eleven patients had sustained monomorphic ventricular tachycardia and two patients had old myocardial infarction without ventricular tachycardia. Functional evidence of slow conduction at the recording site was assessed by pacing at that site and measuring the interval between the stimulus artifact (S) and the onset of the QRS complex in the 12 lead electrocardiogram (ECG). During pacing at 89 of 90 sites without fractionated sinus rhythm electrograms, the S QRS interval was less than 40 ms, a value consistent with rapid propagation of the stimulated wave front away from the pacing site. During pacing at 21 (49%) of 43 sites with fractionated sinus rhythm electrograms, the S-QRS interval was greater than 40 ms (range 40 to 140), consistent with slow conduction at the pacing site (p less than 0.001 versus nonfractionated sites). In 9 of the 11 patients with ventricular tachycardia analysis of the paced QRS configuration, electrograms during induced ventricular tachycardia or programmed stimulation during tachycardia suggested that a site with a long S-QRS interval during pacing was located at or near a ventricular tachycardia circuit. Therefore, fractionated sinus rhythm electrograms are often associated with slow conduction, which may be the substrate for reentrant ventricular tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2913116 TI - Rapid self-terminating ventricular tachycardia induced during electrophysiologic study: a prospective evaluation. AB - The clinical significance of rapid self-terminating ventricular tachycardia induced during electrophysiologic study was prospectively evaluated in three patient groups with clinical ventricular arrhythmias. Group A (11 patients) had inducible rapid self-terminating ventricular tachycardia only (mean cycle length less than or equal to 250 ms and greater than or equal to 10 beats in duration). In Group B (22 patients) induction of this arrhythmia was followed by the induction of sustained ventricular tachycardia. In Group C (82 patients) sustained ventricular tachycardia was induced without preceding rapid self terminating ventricular tachycardia. All clinical characteristics of Group B patients were similar to those of Group C patients but differed markedly from those of Group A patients. Compared with Group A patients, Group B patients had a lower left ventricular ejection fraction (32 +/- 13% versus 52 +/- 17%, p = 0.004) and a greater prevalence of coronary artery disease (82% versus 0%, p less than 0.0001), structural heart disease and a history of clinical sustained ventrical arrhythmias. Similarly, the induced self-terminating ventricular tachycardia differed in Group A and Group B patients. The arrhythmias in Group B patients were more often monomorphic, were more often induced with one or two extrastimuli and had a longer cycle length than those in Group A patients. In Group B patients, the electrophysiologic characteristics of the self-terminating and the sustained induced ventricular tachycardias were similar. Cardioversion was required in 50% of Group B patients compared with 27% of Group C patients (p = 0.038).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2913117 TI - Concealed anterograde accessory pathway conduction during the induction of orthodromic reciprocating tachycardia. AB - The purpose of this study was to determine whether concealed anterograde accessory pathway conduction occurs during the induction of orthodromic tachycardia by an atrial extrastimulus (S2). Sixteen patients with an overt (n = 9) or concealed (n = 7) accessory pathway had inducible orthodromic tachycardia by S2 during an atrial drive (S1) cycle length of 500 to 650 ms. A ventricular extrastimulus (S3) was introduced coincident with the His depolarization resulting from S2 during the longest S1S2 interval that reproducibly induced orthodromic tachycardia. The S1S3 interval was decreased in 10 ms steps until S3 reached ventricular refractoriness. Retrograde accessory pathway conduction of S3 in the presence and absence of S2 was compared at the same S1S3 intervals. In the absence of S2 there was retrograde accessory pathway conduction after S3 in each patient. In the presence of S2, in patients with overt pre-excitation, retrograde accessory pathway conduction after S3 was absent in one patient, prolonged in four patients and present only after long S1S3 intervals in three patients. Only one patient had unchanged retrograde conduction regardless of the presence or absence of S2. In patients with a concealed accessory pathway, retrograde accessory pathway conduction after S3 was absent in five patients and was prolonged in two. Thus, concealed anterograde accessory pathway conduction was present in 15 of 16 patients at the time of orthodromic tachycardia induction. In conclusion, concealed anterograde accessory pathway conduction occurs in a majority of patients with an overt or a concealed accessory pathway during induction of orthodromic tachycardia by an atrial extrastimulus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2913118 TI - Pulsatile diameter and elastic modulus of the aortic arch in essential hypertension: a noninvasive study. AB - A noninvasive evaluation of the aortic arch diameter was performed in 16 subjects with sustained essential hypertension and in 15 normal subjects of similar age, gender and body surface area. In all subjects, measurements were obtained of brachial mean arterial pressure and pulse pressure, cardiac mass (judged on echocardiography) and carotid-femoral pulse wave velocity together with ultrasound determinations of aortic arch diastolic and systolic diameter (suprasternal window). For each subject, pulsatile change in aortic diameter, strain and aortic arch elastic modulus were calculated. Compared with normal subjects, the hypertensive subjects showed an increase in aortic arch diameter (diastolic diameter 29.6 +/- 1.0 versus 25.4 +/- 1.0 mm, p less than 0.01), in elastic modulus (1.071 +/- 0.131 versus 0.526 +/- 0.045 10(5) N.m-2, p less than 0.001) and pulse wave velocity (11.8 +/- 0.5 versus 8.9 +/- 0.3 m/s, p less than 0.001). In the study group, a positive correlation was observed between diastolic aortic arch diameter and mean arterial pressure (r = 0.54, p less than 0.01) and between elastic modulus and cardiac mass (r = 0.60, p less than 0.01). Elastic modulus and age were positively correlated (r = 0.73, p less than 0.01) in hypertensive but not in normal subjects (r = 0.08, NS). This study is the first to demonstrate noninvasively that both the aortic arch diameter and the elastic modulus are increased in patients with sustained uncomplicated essential hypertension. These findings suggest that the increase in elastic modulus could influence the development of cardiac hypertrophy, and that both age and blood pressure act independently as factors that alter the arterial wall of subjects with sustained essential hypertension. PMID- 2913119 TI - Spectrum of findings in a family with nonsyndromic autosomal dominant supravalvular aortic stenosis: a Doppler echocardiographic study. AB - Nonsyndromic familial supravalvular aortic stenosis is an autosomal dominant disorder. However, for many reported families, systematic study of all family members with echocardiographic or hemodynamic techniques has not been performed and degree of penetrance has not been assessed. The supravalvular stenosis in these family members usually is not associated with mental retardation or other characteristics of Williams syndrome. Although some believe that autosomal dominant supravalvular aortic stenosis is part of the spectrum of Williams syndrome, others believe that these are separate entities. Doppler echocardiograms were analyzed on 23 members of a 34 member family with several known to have supravalvular aortic stenosis; 20 studies were performed by the authors and 3 were done elsewhere and made available for review. No family member had mental retardation, characteristic facies or other findings of Williams syndrome. Three of the 34 had supravalvular aortic stenosis requiring surgery. Of 22 members examined echocardiographically who had not had prior surgical repair, 13 had supravalvular aortic stenosis. Echocardiographic findings ranged widely, from calcification of the ascending aorta in a 71 year old man with minimally increased flow velocity (1.7 m/s) to mild narrowing with mildly increased flow velocity in six members to significant narrowing with impressively increased flow velocity (2 to 4 m/s) in seven. In addition, four patients had mild narrowing of pulmonary artery branches and eight had peak pulmonary artery flow velocity above normal. This study demonstrates complete penetrance with extremely variable expression in this family with autosomal dominant supravalvular aortic stenosis and emphasizes the importance of using echocardiographic techniques in studying the family members who are suspected of having an inherited cardiovascular disease. PMID- 2913120 TI - Long-term results of amiodarone therapy in patients with recurrent sustained ventricular tachycardia or ventricular fibrillation. AB - Four hundred sixty-two patients, all with either documented spontaneous sustained ventricular tachycardia or cardiac arrest unresponsive to other antiarrhythmic drugs (2.6/patient), were treated with amiodarone. Thirty-five patients (7.6%) failed to respond or died during the initial oral or intravenous loading phase. The remaining 427 patients were discharged on treatment with oral amiodarone and followed up for up to 98 months. Recurrence of ventricular tachycardia or sudden cardiac death at 1, 3 and 5 years by life-table analysis was 19%, 33% and 43%, respectively, for patients discharged on amiodarone therapy. The sudden cardiac death rate was 9%, 15% and 21%, respectively, at 1, 3 and 5 years. Side effects were reported by 45% of patients after 1 year, by 61% after 2 years and by 86% after 5 years. Amiodarone was discontinued because of side effects in 14%, 26% and 37% of patients after 1, 3 and 5 years, respectively. Incidence rates of recurrence of arrhythmia, sudden cardiac death and side effects were highest in the early months and then decreased. By multivariate analysis, advanced age, low ejection fraction and a history of cardiac arrest were independent risk factors for sudden cardiac death during amiodarone therapy. PMID- 2913121 TI - Assessment of regional myocardial blood flow with myocardial contrast two dimensional echocardiography. AB - It was hypothesized that regional myocardial blood flow could be measured using myocardial contrast echocardiography. Accordingly, arterial blood was perfused into the coronary circulation in 16 dogs. In Group 1 dogs (n = 8), blood flow to the cannulated left circumflex artery was controlled with use of a roller pump, whereas in Group 2 dogs (n = 8) blood flow to the left anterior descending coronary artery was controlled by a hydraulic occluder placed around it. Sonicated microbubbles (mean size 4 microns) were used as the contrast agent. In Group 1 dogs the microbubbles were injected subselectively into the left circumflex artery, whereas in Group 2 dogs they were injected selectively into the left main coronary artery and two-dimensional echocardiographic images were recorded. Computer-generated time-intensity curves were derived from these images and variables of these curves correlated with transmural blood flow measured with radiolabeled microspheres. A gamma-variate function (y = Ate-alpha t) best described the curves, and alpha (a variable of curve width) correlated well with transmural blood flow at different flow rates in all Group 1 and Group 2 dogs (mean r = 0.81 and 0.97, respectively). Other variables of the curve width also correlated well with myocardial blood flow, but peak intensity had a poor correlation with myocardial blood flow in both groups of dogs (r = 0.39 and r = 0.63, respectively). When data from all dogs were pooled, Group 1 dogs still showed good correlation between variables of curve width and myocardial blood flow (r = 0.81); Group 2 dogs did not (r = 0.45). The difference between the two sets of dogs was related to the site of contrast agent injection. It is concluded that measurement of the transit time of microbubbles through the myocardium with two-dimensional echocardiography accurately reflects regional myocardial blood flow. Although injection of contrast agent selectively into the left main coronary artery only allows measurement of relative flow, it may be feasible to measure absolute flow by injecting contrast agent subselectively into a coronary artery. Myocardial contrast echocardiography may, therefore, offer the unique opportunity of simultaneously assessing regional myocardial perfusion and function in vivo. PMID- 2913122 TI - Influence of loading patterns on peak length-tension relation and on relaxation in cardiac muscle. AB - To analyze the influence of loading patterns on cardiac pump performance and cardiac relaxation [corrected], the effects of preload on peak length-tension relation [corrected] and of systolic load clamps on peak length-tension relation and on relaxation were analyzed in isolated cat papillary muscles. Preload reduction and early loading clamps induced a shift to the left of the peak length tension relation, that is, a smaller muscle length for the same tension at peak shortening. Unloading clamps induced a shift to the right of the peak length tension relation, that is, a larger muscle length for the same tension at peak shortening. The effects of load clamps on relaxation depended on when they were applied during isotonic shortening. Changes induced by load clamps could not be summarized in terms of enhanced or delayed relaxation, illustrating that shortening duration, isometric tension decline and isotonic lengthening have different determinants. In conclusion, not only peak or mean systolic pressure but also the entire loading pattern has to be taken into account whenever pressure-volume data or relaxation variables are interpreted. PMID- 2913123 TI - Catheter ablation of accessory pathways using radiofrequency energy in the canine coronary sinus. AB - Ablation of a left-sided accessory pathway with high energy direct-current shocks delivered by an electrode catheter in the coronary sinus is associated with the risk of coronary sinus rupture. The safety and effectiveness of closed chest catheter desiccation in the coronary sinus with use of radiofrequency energy was studied. Radiofrequency energy (174 +/- 74 J) was applied between the distal electrode of a standard electrode catheter placed 3 to 6 cm inside the coronary sinus and a large posterior chest wall patch in 16 dogs. No arrhythmias or hemodynamic changes were observed. Three dogs were killed approximately 1 h after ablation and 13 after 2 to 4 weeks. Lesions in the atrioventricular (AV) sulcus were observed in 14 of 16 dogs. Lesions were 11.6 +/- 6 mm in length, 4.3 +/- 2.3 mm in width and 2.8 +/- 1.4 mm in depth. Microscopic examination showed well circumscribed areas of necrosis and fibrosis in the fat of the AV sulcus. The media and intima of the circumflex coronary artery were not involved nor was the endocardium or mitral apparatus damaged in any dog. Coronary sinus thrombus was present in 3 of 16 dogs. Large amounts of radiofrequency energy can be safely applied to the coronary sinus. The size and location of the lesions produced suggest that this technique may be useful for the interruption of left-sided accessory AV connections in humans. PMID- 2913125 TI - Clinical research in the United States--a threatened activity. PMID- 2913124 TI - Diet and cholesterol guidelines and coronary heart disease. PMID- 2913126 TI - The educational role of thrombolytic therapy. PMID- 2913127 TI - Color Doppler diagnosis of left ventricular pseudoaneurysm. PMID- 2913128 TI - President's address. Allergy: at the academic/clinical interface. PMID- 2913129 TI - Suppression of the late cutaneous response by immunotherapy. AB - In a prospective, double-blind, placebo-controlled study, we examined the effect of mountain cedar (MC) immunotherapy on the MC-induced late cutaneous response (LCR). Fourteen MC-sensitive patients were intradermally skin tested before and after immunotherapy with MC extract. We measured the size of the wheal at 15 minutes and the area of tissue swelling at 6 hours. Patients were matched by the size of the LCR and started receiving either MC immunotherapy or placebo immunotherapy. MC-specific immunoglobulins (MC sIgG, MC sIgG1, MC sIgG4, and MC sIgE) were measured by ELISA. Symptom-medication scores (SMSs) were recorded on a daily basis during the MC season and tabulated at the end of the study. Comparison of the 14 paired patients revealed no significant differences between MC-treated and placebo-treated groups in preimmunotherapy MC sIgG1 and SIgG4. However, when MC immunotherapy was compared to placebo immunotherapy, patients receiving MC immunotherapy developed significantly higher MC sIgG1 (p less than 0.04) and MC sIgG4 (p less than 0.01) after immunotherapy. Patients receiving MC immunotherapy also demonstrated significantly greater suppression of the LCR after immunotherapy (p less than 0.005) with the postimmunotherapy LCR correlating significantly with both MC sIgG4 (rs = 0.715; p = 0.008) and cumulative dose of MC received (rs = 0.808; p = 0.004). MC sIgE was similar in both groups after immunotherapy. The reduction in SMSs in the MC-treated group did not reach significance, nor was there a correlation of SMSs with MC sIgE, sIgG, sIgG1, or sIgG4.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2913130 TI - Plasma concentrations of complement-activation complexes correlate with disease activity in patients diagnosed with isolated central nervous system vasculitis. AB - Isolated central nervous system (CNS) vasculitis is rare medium- sized vessel disease limited to intracerebral vessels. The two most common symptoms of this inflammatory disorder observed at entry to a hospital are headaches and mild memory deficits. Further progression of this disease may result in focal neurologic alterations and seizures. Currently, the most common laboratory abnormality noted is an elevated erythrocyte sedimentation rate. The complement (C) system is known to play a role in many inflammatory processes; it may also be involved in CNS vasculitis. In this longitudinal study of patients with CNS vasculitis, we detected C activation by highly sensitive and specific assays that are capable of identifying breakdown products formed after C activation: C3a des arg, C4a des arg, C5a des arg, C1rC1s-C1-inhibitor complex, and terminal C complex (C5b-9). We present two cases of documented CNS vasculitis in which serial measurements of these C-activation products correlate with disease activity. Our results indicate that a temporal association exists between C activation and the clinical presentation of CNS vasculitis. We conclude that physicians should monitor C-activation by-products in plasma when they attempt to follow the clinical course of CNS vasculitis. PMID- 2913131 TI - Allergenic pollens in the southern Mediterranean area. AB - In the Mediterranean area there are characteristic climatic conditions (mildness of winter, summer dryness, etc.) that facilitate the growing of a typical vegetation with production of allergenic pollen, such as those from Parietaria and Olea europaea, very different from that of central and northern Europe. We present in this article the results of an 8-year pollen count in the atmosphere of Naples, Italy. The pollen content was examined with a volumetric spore trap (Lanzoni VPPS-2000) like that of Hirst. The results of the pollen counts were subsequently compared with results of skin tests of patients born and still living in and around Naples to determine the pollinosis of that area. We found that the most important allergenic pollen in the Naples area is Parietaria, with very long-lasting periods of pollination. The first period, more important, occurring from March to July, and the second period of much lower intensity, occurring from the end of August to the end of October. Pollen allergy to Parietaria was found to be present in 82.02% of pollen-allergic patients. It was followed by Gramineae (32.12%), Olea (23.11%), and Artemisia vulgaris (17.08%). These data are quite different from data of the pollinosis in northern Italy and in the northern Mediterranean area, as well as the southern coast of France, where allergic sensitization to Poaceae is the most important. PMID- 2913132 TI - Influence of food on the absorption of albuterol Repetabs. AB - A study was conducted in 12 healthy, nonsmoking male volunteers to examine the effect of food intake on the absorption profile of albuterol repeat-action tablets. This randomized crossover study consisted of two phases separated by a 1 week washout period. All subjects fasted 10 hours preceding drug administration. Each subject received two 4 mg albuterol repeat-action tablets with and without a high fat content breakfast. Plasma albuterol concentrations were determined by a gas chromatographic/mass spectrophotometric assay. Relative bioavailability was assessed by comparing areas under the plasma-albuterol concentration time curves as well as peak concentrations and time to peak concentration. No significant differences were noted between the two treatment phases in the area under the curve or peak plasma concentrations. The areas under the curve were 100 and 105 hr.ng/ml when the drug was administered with and without food, respectively. The corresponding peak plasma concentration values were 9.4 and 10.4 ng/ml, respectively. The only significant difference observed was in the maximum time to reach peak plasma concentrations, which was delayed by about 1 hour when the drug was administered with food. Therefore, food has minimal effect on the absorption of albuterol from repeat-action tablets. PMID- 2913133 TI - Characterization with monoclonal and polyclonal antibodies of a new major allergen from grass pollen in the group I molecular weight range. AB - We have purified a 24/25 kd allergen from orchard grass pollen (Dactylis glomerata) that has an allergenic potency similar to that of the major group I allergen. We provisionally named this allergen grass 4B1 after the monoclonal antibody used for its identification and purification. This monoclonal antibody was obtained by immunizing mice with whole Lolium perenne-pollen extract and by screening the antibody producing hybrids for reactivity with Dactylis glomerata pollen extract. Grass 4B1 is physicochemically separable from the group I allergen. Polyclonal rabbit antibodies to grass 4B1 do not react with group I allergen or vice versa. Ninety-five sera with IgE antibodies to grass pollen were tested for IgE antibodies to grass 4B1, and greater than 90% was positive in this test. The median response to grass 4B1 was 70% of that to Lol p I. PMID- 2913134 TI - Airway refractoriness to adenosine 5'-monophosphate after repeated inhalation. AB - Adenosine-5'-monophosphate (AMP) is a bronchoconstrictor agonist in subjects with atopic and nonatopic asthma. In this study we have investigated the effect of repeated airway challenge with AMP in 10 atopic, subjects without asthma. At the first visit, subjects had repeated inhalation challenges with increasing doubling concentrations of AMP, and the provocation concentration required to reduce FEV1 by 20% of baseline was determined (PC20 AMP). When the FEV1 had returned to within 5% of the baseline, the AMP challenge test was repeated on a further one or two occasions. When the maximum concentration of AMP (400 mg/ml) failed to produce a PC20, a bronchial provocation test with histamine was performed and the PC20 was determined. On the second visit, the effect of three consecutive inhalation challenge tests with histamine on the airway response to this agonist was determined. On the third visit, the duration of induced refractoriness to AMP was assessed. With the first AMP challenge, all subjects demonstrated bronchoconstriction with a geometric mean (GM) PC20 of 332 mg/ml. With a second AMP challenge, five of the 10 subjects became refractory and failed to achieve a PC20. In the remaining five subjects, the GM PC20 increased from 110 to 583 mg/ml. With a third AMP challenge, these subjects also failed to achieve a PC20. The initial GM PC20 histamine for the group was 22.9 mg/ml, which did not change significantly with two further histamine challenges or when the airways were refractory to AMP, suggesting that loss of AMP effect was not related to loss of contractility of airway smooth muscle or down regulation of H1-histamine receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2913135 TI - Immunodeficiency in patients with hemophilia: an underlying deficiency and lack of correlation with factor replacement therapy or exposure to human immunodeficiency virus. AB - Nineteen patients with hemophilia, five of whom were classified as untreated, were immunologically evaluated by the measurement of cell surface markers, natural killer cell activity, mitogenic responses, polyclonal immunoglobulin production, and serologic evidence of human immunodeficiency virus infection. No correlations were found between human immunodeficiency virus infection and immune abnormalities, or between patients who did or did not receive factor therapy, although the abnormalities were more profound in those who received treatment. An intrinsic B cell abnormality in patients with hemophilia is suggested. PMID- 2913136 TI - Outcome of long-term hospitalization for asthma in children. AB - Children whose asthma continues to be poorly controlled with outpatient management are often referred to a long-term hospital program for care. Although these programs have been in existence since the 1950s, there has been no systematic study of their effectiveness. The purpose of the present study was to determine outcome in 103 children discharged consecutively after a long-term hospitalization. These children had both severe asthma and significant psychologic problems. Eighty-three of the 103 children had required continuous or frequent intermittent steroids for asthma control. In the year before admission, they had been hospitalized for asthma a mean of 2.6 times for 11.8 days and had had 4.6 visits to emergency rooms and 6.6 visits to physician offices for acute wheezing. Use of medical resources for asthma decreased significantly in the year after long-term hospitalization compared to the year before hospitalization (hospitalization: -34%, p less than 0.0001; hospital days: -39%, p less than 0.0002; emergency room visits: -46%, p less than 0.00001; physician office visits for acute asthma, -42%; p less than 0.00001; and a composite score giving increasing weight to more intensive and costly care: -30%, p less than 0.0001). Long-term hospitalization for children with asthma not responsive to outpatient management is associated with improvement in their use of medical resources. PMID- 2913137 TI - Isolation and characterization of heat-stable allergens from shrimp (Penaeus indicus). AB - Shrimp are among the more common causes of immediate hypersensitivity reactions to food. To characterize better the allergenic substances within shrimp, extracts from heated shrimp were systematically examined with solid-phase radioimmunoassay and sera from patients clinically sensitive to shrimp. Two heat-stable protein allergens, designated as Sa-I and Sa-II, were identified from boiled shrimp (Penaeus indicus) extracts. Sa-I was isolated by ultrafiltration, Sephadex G-25, and diethylaminoethyl-Sephacel chromatography, whereas, Sa-II, the major allergen, was purified by successive chromatography on diethylaminoethyl Sephacel, Bio-Gel P-200, and Sepharose 4B columns. Sa-I, was homogeneous by polyacrylamide gel electrophoresis (PAGE), elicited a single band on sodium dodecyl sulfate-PAGE corresponding to a molecular weight of 8.2 kd. Sa-II was also found to be homogeneous by PAGE, crossed immunoelectrophoresis, and immunoblotting. On sodium dodecyl sulfate- PAGE, it elicited a single band with a molecular weight of 34 kd. Sa-II was found to contain 301 amino acid residues and was particularly rich in glutamate/glutamate and aspartate/asparagine. Solid phase radioimmunoassay-inhibition studies revealed that Sa-I and Sa-II share 54% of the allergenic epitopes, suggesting that Sa-I may be a fragment of Sa-II. PMID- 2913138 TI - Immunotherapy with cat- and dog-dander extracts. IV. Effects of 2 years of treatment. AB - Thirty-five patients (20 children and 15 adults) with animal-dander asthma completed 2 years of immunotherapy with partly purified and standardized cat- or dog-danger extracts. The first year of the study was performed double-blind with a placebo-treated control group. These 15 patients were transferred to active treatment for a second year. All patients were followed by use of the skin prick test (SPT), allergen and histamine bronchial challenges, and tests for allergen specific IgE, IgG1, and IgG4 levels. In the group treated with active extracts for 2 years (group A), the previously reported decrease in bronchial responsiveness to cat extract (p less than 0.001) and histamine (p less than 0.01) was even more pronounced after the second year. After 1 year of active treatment in the original placebo group (group B), a significant decrease in the bronchial responsiveness to cat extract was noted (p less than 0.001). The responsiveness to histamine was decreased only in the patients treated with cat dander extracts (p less than 0.05). A significant decrease in the SPT (p less than 0.001) and an increase in the allergen-specific IgE (p less than 0.001) and IgG4 (p less than 0.001) was also noted in patients (group B) treated with cat dander extracts. The side effects in the two groups (A and B) were negligible, except for some systemic side effects, especially among the children during the initial phase of immunotherapy. The symptoms were mild and responded promptly to treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2913139 TI - The effects of theophylline on the physical performance and work capacity of well trained athletes. AB - Theophylline, a pharmacologic agent presently permitted during international sporting competition, has come under scrutiny because of the suggestion that it may be ergogenic. This study examined the effects of serum theophylline levels of 10 to 20 mg/L and the administration of a placebo on selected measures of physical performance and work capacity to determine any ergogenic outcomes. Seven male and three female elite athletes from a variety of team sports and aged 18 to 30 years participated in the study. The variables measured were height, mass, maximal oxygen consumption, muscular endurance, muscular power, muscular strength, FVC, FEV1, and reaction time. When the scores obtained after ingestion of theophylline and a placebo with a double-blind, crossover technique were compared, no significant difference was found for any of these variables. A two way analysis of variance of FEV1 scores obtained before and after maximal exercise revealed no significant "F" ratios. This indicated that none of these trained athletes demonstrated exercise-induced asthma and that there was no difference in airway resistance after maximal exercise while they were under the influence of theophylline or placebo. We conclude that no ergogenic effects were attributable to theophylline therapy which should therefore remain an acceptable means of management of athletes with asthma participating in international sporting events. PMID- 2913140 TI - Flexible fiberoptic rhinoscopy in the diagnosis of sinusitis. AB - Two-hundred forty-six patients with undiagnosed headache, after unrewarding neurologic evaluation, were referred to an allergy clinic and were evaluated both by routine sinus radiographs and flexible fiberoptic rhinoscopy. Ninety-eight patients had only rhinoscopic evidence of sinusitis (group I), 84 patients had both rhinoscopic and radiographic evidence of sinusitis (group II), and 64 patients had neither rhinoscopic nor radiographic evidence of sinusitis (group III). Antibiotic treatment resulted in relief of headaches in 94% of group I, 75% of group II, and 5% of group III patients. The distribution of sinus infections found by both rhinoscopy and radiography were similar; however, rhinoscopy may have found the disease earlier than radiography. Flexible fiberoptic rhinoscopy is an efficient method for the office diagnosis of sinusitis. PMID- 2913141 TI - Obtaining geriatric patient consent. PMID- 2913142 TI - Behavioral psychological intervention. PMID- 2913143 TI - Retirement attitudes and health status of preretired and retired men and women. PMID- 2913144 TI - Gynecological health needs of elderly women. PMID- 2913145 TI - Glimpses of China and Chinese elders. PMID- 2913146 TI - Learning to care about gerontological nursing. PMID- 2913147 TI - Impact of a recapping device on venepuncture-related needlestick injury. AB - In a 33-month prospective analysis of needlestick injuries, venepuncturists working under Centers for Disease Control (CDC) guidelines for handling used needles were shown to incur a needlestick injury for every 3,175 to 4,006 needle handling procedures. On the other hand, users of a simple device designed to reduce the risk of injury when recapping used needles were shown to incur a needlestick only once in every 16,100 venepunctures performed (P less than 0.001). This represents a fourfold reduction in the rate of needlestick injuries. We thus question the effectiveness of the CDC nonrecapping policy. PMID- 2913148 TI - Urinary tract infection following instrumentation for urodynamic testing. AB - After identifying a temporal cluster of urinary tract infections in patients who had undergone urodynamic procedures, we examined the techniques within the urodynamic laboratory and retrospectively reviewed charts of all 155 patients tested in the previous six months. The rate of acquired urinary tract infections was 18.7%. Risk factors for infection included undergoing cystometrograms and being subject to the first procedure performed in a day. Technical errors in the performance of the urodynamic studies included failure to completely disassemble the apparatus upon completion of a procedure, failure to use sterile components, and lapses in aseptic technique. Bacteria implicated in the outbreak were isolated from tubing, transducers, and flush solutions. After the institution of appropriate technique, all patients tested in the subsequent six months were followed. The rate of acquired urinary tract infection dropped to 5%. Urodynamic apparatus should be completely disassembled following the completion of a procedure; reassembly using sterile components should occur immediately prior to the next procedure; aseptic technique should be maintained; and patients should undergo routine urine screening before a procedure. Surveillance of urodynamic procedures may reveal correctable flaws in technique. PMID- 2913149 TI - Management of HIV-1 infection in the hospital setting. PMID- 2913150 TI - Utilization review and management: a brief analysis of a growth industry. AB - Current evidence concerning the prevalence of inappropriate care indicates that there is an opportunity for significant utilization and cost reductions. Although the efficacy of some methods of utilization control has been demonstrated, the clinical impact and safety of these techniques are unclear. Although financial incentives have been successful in nonhealth industries, there is no evidence that fiscal rewards will eliminate inappropriate use rather than necessary care. Both short- and long-term quality assurance monitors should be combined with any utilization control method promoting "appropriate" use of inpatient beds and hospital services. PMID- 2913151 TI - Site-specific mutagenesis of the class I regulatory element the Q10 gene allows expression in non-liver tissues. AB - Classical transplantation Ag are found on nearly all cells, whereas Ag encoded by the genes of the Qa/Tla region have a restricted tissue distribution. To investigate the cause of these different patterns of expression, we have compared the regulatory regions of Q10, a Qa region gene that is expressed only in liver, with those of H-2Ld. Gel retardation analysis shows that the nuclear factor (rI) that binds to the inverted repeat (TGGGGATTCCCCA) of the class I regulatory element (CRE) present in H-2Ld and other classical class I genes does not bind to the equivalent region of the Q10 gene. However, the Q10 CRE binds another nuclear factor (rII) that binds to the H-2Ld CRE. The sequence of the Q10 CRE differs from the sequence present in classical class I genes by three nucleotides, two of these changes are within the inverted repeat sequence (TGaGGAcTCCCCA) and disrupt the region of dyad symmetry. We have used site-specific in vitro mutagenesis to individually change these two nucleotides and have investigated the ability of this region to promote transcription with and without these substitutions. A change of either base restores transcriptional activity in chloramphenicol acetyl transferase assays and allows for binding of the rI nuclear factor. These results suggest that the failure of the Q10 CRE to bind the rI nuclear factor may play a role in preventing Q10 expression in tissues other than the liver and fetal yolk sac. Thus, the dichotomy between the widespread tissue expression of classical class I genes and the restricted tissue expression of class I genes of the Qa/Tla region may be due in part to differences in the cis acting regulatory sequences that interact with trans-acting nuclear factors to direct transcription. PMID- 2913152 TI - Effect of recombinant murine tumor necrosis factor on hemopoietic reconstitution in sublethally irradiated mice. AB - Intravenous bolus administration of a single 2-micrograms dose of murine rTNF alpha to BALB/c mice 20 h before sublethal total-body irradiation (7.5 Gy) conferred significant protection against radiation-induced leukopenia. Murine rTNF-alpha administration not only reduced the decline of neutrophil and total blood cell counts after radiation, but also accelerated the subsequent normalization of peripheral blood cell counts. This was accompanied by accelerated regeneration of primitive hematopoietic progenitors, as determined by the in vivo spleen CFU assay, and the in vitro assay of the more mature hematopoietic cell compartment. This demonstrates that pretreatment with murine rTNF-alpha enhances hematopoietic reconstitution after sublethal irradiation, and indicates a possible therapeutic potential for this agent in the treatment of radiation-induced myelo-suppression. PMID- 2913153 TI - Biosynthesis of properdin. AB - Properdin (P) is synthesized by the human promyelocytic cell line, HL-60, after differentiation with DMSO. The secreted P was physiochemically indistinguishable from purified plasma P. It was polymerized and able to bind to C3IBb-Sepharose but not to C3i-Sepharose. No extracellular precursor was present. The intracellular form, detected between 1 and 4 h after labeling, was similar but had a slightly lower Mr. It also bound reversibly to C3iBb-Sepharose, and polymers could be demonstrated by cross-linking. Pulse-chase experiments suggested the existence of an earlier, but undetectable, intracellular precursor(s). This form could not be immunoprecipitated even when harsh solubilization conditions and/or antibodies against reduced and denatured P were utilized. Studies with endoglycosidases F and H and tunicamycin indicated that the detectable intracellular precursor contains high mannose N-linked carbohydrate that is processed to the complex form before secretion. The sugars are not required for polymerization, secretion, or functional activity, or responsible for the electrophoretic heterogeneity. Polymerization of P is therefore an early intracellular event, perhaps carefully controlled to prevent anomalous aggregation. PMID- 2913155 TI - A biotin-avidin sandwich ELISA for quantification of intact complement component C9. The sera from hereditary C9 deficient individuals completely lack C9. AB - A two-site sandwich ELISA method was developed for quantitating intact C9 protein using MoAb P40 (anti-C9b antibody). This antibody reacted with monomeric C9 but not with polymerized C9. MoAb P40 was used as a capture antibody and MoAb X195 (anti-C9a antibody) as a detection antibody. This method is highly sensitive and can detect approximately 0.5 ng/ml of native C9. No cross-reactivities of either C6, C7, or C8 were observed even at concentrations of 10 micrograms/ml per component. In addition, this method allows for measurement of only intact C9 molecules, eliminating the interference of polymerized C9 or inactivated C9. Using this assay, no C9 at all was detected in sera from inherited C9 deficient individuals, including both healthy blood donors and patients with meningococcal meningitis; although by hemolytic assay, C9 levels were reported to be less than 0.2% those of NHS. Therefore, this two-site sandwich ELISA method can replace the hemolytic assay, and is especially useful for measuring small amounts of C9 in serum. PMID- 2913154 TI - Production of hybrid hybridomas based on HAT(s)-neomycin(r) double mutants. AB - A detailed procedure is described for the preparation of hybrid hybridomas, that produce bispecific antibodies. This is achieved by fusing two hybridoma cell lines that are phenotypically distinct (HAT(s)/neo(r) and HAT(r)/neo(s)) and thereby allow for the selection of the appropriate hybrid cells. HATs mutants were obtained from one of the two fusion partners by 8-azaguanine treatment; these mutant phenotypes were found in an unexpected high frequency. For the introduction of the dominant neo(r) marker gene in one of the HAT(s) fusion partners, a retroviral vector was used in order to obtain a high efficiency of gene transfer. Our method was very effective in the production of hybrid hybridomas, so-called quadromas. The detection of bispecific antibodies was based on simultaneous binding by one antibody of two different antigens, or on the presence of two different H chain isotypes in this molecule. PMID- 2913156 TI - Quantitation of a cationic antimicrobial granule protein of human polymorphonuclear leukocytes by ELISA. AB - The quantitation of CAP57, a highly hydrophobic, native cationic antigen of human polymorphonuclear leukocytes has been achieved using ELISA. An important feature determining the sensitivity and precision of the ELISA was the reduction of non specific protein-protein binding, particularly in the inhibition assays, thus eliminating high backgrounds obtained with presently available methodology. Washing of the solid phase-bound antigen and blocking of the non-specific binding sites using a potassium phosphate buffer containing heparin largely contributed to this increased sensitivity. The inhibition assays were conducted using antigen concentrations over the range of 0.9-120 ng. The assay is highly specific and can be performed using monoclonal antibodies and polyclonal antibodies. Non-specific reactions were observed only when high concentrations of antigen (greater than 100 ng) were present in the inhibition mixture. The technique as described is extremely simple, highly reproducible and could be of value in the detection of cationic antimicrobial proteins in the clinical setting in the future. PMID- 2913157 TI - Production and characterization of monoclonal antibodies against human glycoalbumin. AB - Hybridomas secreting monoclonal antibodies specific for nonenzymatically glycated albumin were produced by fusion of SP2/0 myeloma cells with spleen cells from BALB/c mice immunized with unreduced nonenzymatically glycated albumin prepared from human plasma. Wells containing hybridomas secreting antibodies against glycoalbumin were identified by binding, in an enzyme-linked immunosorbent assay, to glycoalbumin isolated from human plasma or to albumin that had been glycated in vitro. The colony designated A717, which secreted antibodies discriminating between glycated versus unglycated albumin, was cloned four times by limiting dilution and used for further study, performed with monoclonal antibody purified from mouse ascites fluid. Specificity of A717 was demonstrated by immunoblotting and by ELISA, wherein the monoclonal antibody reacted preferentially with glycated albumin but insignificantly with unglycated albumin. Immunoblotting of human plasma with A717 on nitrocellulose yielded a single band, the electrophoretic mobility of which corresponded with that of authentic glycated albumin, indicating site specificity for glycated epitopes residing in albumin but not in other nonenzymatically glycated serum proteins. A717 differs from other antibodies raised against glycated albumin and other proteins, which recognize glycated residues only after reductive conversion to glucitol-lysine and which do not discriminate between different glycated proteins. Thus, this report describes the establishment of the first hybridoma secreting monoclonal antibody raised against unreduced glycated albumin, which is the physiologic form occurring in vivo, and for the epitope when it resides in albumin but not other proteins. PMID- 2913158 TI - Purification of monoclonal antibodies raised against prostate-specific acid phosphatase for use in vivo in radioimaging of prostatic cancer. AB - In developing diagnostic reagents for the radioimaging of prostatic cancer, methods were optimized for the purification of two mouse IgG1 monoclonal antibodies raised against prostate-specific acid phosphatase and produced in cell culture. Two different two-step methods were selected. One method consisted of two successive ion exchange chromatographic steps on Mono S and Mono Q; in the other method, Mono S chromatography was followed by hydrophobic interaction (Alkyl Superose) chromatography. In both cases, fast protein liquid chromatography (FPLC) instrumentation was used. The antibodies were purified from cell culture media containing fetal calf serum (1-5%). Highly pure (greater than 95%) IgG1 antibodies, free of contaminating serum-derived proteins or column materials, were obtained in good yield (greater than 90% recovery). The purified antibodies completely retained their immunological reactivity towards prostate specific acid phosphatase and were sterile and pyrogen-free. Since the monoclonal antibodies produced were intended for applications in vivo, an essential feature of the methods selected was the availability of in situ cleaning procedures for sterilization of the gel materials and for the inactivation of viruses and pyrogens in the gels. The methods developed could be readily scaled up for preparative purposes. PMID- 2913159 TI - An improved latex agglutination-inhibition test for the detection of human chorionic gonadotropin in urine. AB - A commercially available slide latex agglutination-inhibition test for pregnancy was used in a tube modification for the detection of human chorionic gonadotropin (hCG) in urine. The tube method used 100 microliters sample and small quantities of reagents which were mixed continuously for 30 min. The results obtained, based on flocculation, were 15-30-fold better than those obtained by slide agglutination using spiked samples or urine samples from pregnant women. The lowest concentration of hCG detected in the spiked samples was 31 IU/l. When 43 clinical specimens were examined, the tube method detected four more samples than the 18 detected by the slide method. A good correlation (r = 0.96) was observed between the two methods in the determination of the hCG content in the positive samples. PMID- 2913160 TI - Time-resolved fluoroimmunoassay of 5-methyl-2'-deoxycytidine employing europium labeled antigen as tracer. AB - We describe a solid-phase fluoroimmunoassay, based on competition between europium-labeled 5 MeCyd (5-methylcytidine) and sample 5MedCyd (5-methyl-2' deoxycytidine) for polyclonal anti-5MedCyd antibodies (rabbit). Europium labeling of antigen was performed using a novel polylysine-5MeCyd conjugate. Standard and sample preparations containing 5MedCyd inhibited the binding of the europium labeled 5MeCyd to the antibody molecules. A second antibody, directed against rabbit IgG, was coated on the solid phase, and bound the IgG-5MeCyd-polylysine europium complex, giving rapid and complete separation of antibody-bound and free antigen. The measuring range was from 3.7 to 2500 pmol of 5MedCyd per assay. A good correlation between the results obtained with TR-FIA and HPLC was demonstrated when the methods were applied to the measurement of methylation in various DNA samples, enzymatically hydrolyzed to their constituent deoxyribonucleosides. This new TR-FIA possesses the same advantages (high sensitivity, wide assay range, rapidity, simplicity, and low cost) as the previous assay developed in our laboratories. The superiority of the new system is based on (i) its low inter- and intra-assay variation, (ii) low antiserum consumption, and (iii) a protocol, which permits the use of second-antibody coated microtitration strips common to other assays. PMID- 2913161 TI - Simultaneous measurement by flow cytometry of phagocytosis and hydrogen peroxide production of neutrophils in whole blood. AB - Bacterial ingestion and hydrogen peroxide production by polymorphonuclear leukocytes (PMN) were simultaneously measured using flow cytometry and 2',7' dichlorofluorescein diacetate and fluorescent Staphylococcus aureus. Only 100 microliters of a whole blood specimen were required for these determinations, and the results were found to be independent of the absolute numbers of PMN, making the purification and adjustment of PMN numbers unnecessary. A positive correlation between phagocytosis and hydrogen peroxide production by individual PMN was demonstrated in healthy adults. PMID- 2913162 TI - Detection and reduction of protein A contamination in immobilized protein A purified monoclonal antibody preparations. AB - Protein A chromatography is an excellent technique for the purification of monoclonal antibodies. However, the presence of Protein A in therapeutic monoclonal antibody preparations due to leaching has been linked with toxicity in animals and humans. Two sandwich ELISAs were developed to monitor Protein A column leaching: (1) rabbit anti-Protein A for capture and anti-Protein A F(ab')2 HRP for detection; and (2) rabbit anti-Protein A for capture and anti-Protein A biotin for detection. The biotin ELISA is sensitive to the subnanogram range. In addition, these assays were used to develop DEAE and gel filtration chromatography techniques that substantially reduce Protein A levels in monoclonal antibodies purified by Protein A chromatography. PMID- 2913163 TI - Adolescent substance abuse. PMID- 2913164 TI - State of Georgia's new informed consent law. PMID- 2913165 TI - A perspective on alternative delivery systems. PMID- 2913166 TI - Political involvement: the key to doctor-friendly legislation. PMID- 2913167 TI - Third Party Payors' view of AIDS. PMID- 2913168 TI - Repeat teen deliveries in Fulton County. PMID- 2913169 TI - Surgical treatment of abdominal aortic aneurysms using cell saver. PMID- 2913170 TI - Toward 9 by '90: reducing infant mortality. PMID- 2913171 TI - Pediatric oncology update. PMID- 2913173 TI - Signs of ectopic pregnancy. PMID- 2913172 TI - Anaphylactoid reaction to diflunisal. PMID- 2913174 TI - Patient satisfaction and continuity of care. PMID- 2913175 TI - Papanicolaou smear techniques. PMID- 2913176 TI - Effectiveness of follow-up reminder methods. PMID- 2913177 TI - Family in family medicine. PMID- 2913178 TI - Chlamydia trachomatis genital infections in a community-based family practice clinic. AB - Primary care physicians must become aware of the epidemiology and current diagnostic and management approaches to genital infections caused by Chlamydia trachomatis, since they are the most common sexually transmitted diseases in the United States. Clinical information was obtained on 282 sexually active female and 54 male patients aged between 14 and 44 years presenting for either asymptomatic physical examination or urogenital symptoms at a community-based family practice clinic that primarily serves middle socioeconomic class patients. A direct fluorescein-conjugated monoclonal antibody staining test for C trachomatis was found to be positive in 34 (12 percent) of 282 women and 15 (28 percent) of 54 men. Two (11 percent) of 19 pregnant women were found to be infected. Significantly more women presenting with urogenital symptoms or as a sexual contact of a symptomatic partner or those with abnormal findings on physical examination were found to have a positive test than were those who had no symptoms and no abnormal findings on physical examination. Similar trends were found in men, but were not statistically significant. It is recommended that primary care physicians presumptively treat those patients who have urogenital symptoms or have been exposed to sexual partners with urogenital symptoms and test asymptomatic patients who have signs of a possible C trachomatis infection. PMID- 2913179 TI - Physician and patient determinants of difficult physician-patient relationships. AB - In an effort to account for the effects of both physician and patient characteristics in understanding difficult physician-patient relationships, family physician participants in the Michigan Research Network, a practice-based research network in the state of Michigan, were assessed for their perceptions of "difficult" patients. Twenty-two family physicians responded to a mail survey in which they selected from among their respective practices a sample of patients whose care they considered to be particularly difficult. This sampling procedure resulted in a total of 205 difficult patients. Physicians' perceptions of these patients were obtained through ratings of the applicability of 40 behavioral and physical characteristics drawn from the literature. Factor analysis of these data resulted in the identification of two factors underlying physicians' perceptions of difficult patients: medical uncertainty, characterized by particularly vague, difficult to describe, undifferentiated medical problems; and interpersonal difficulty, reflected in a perceived abrasive behavioral style. In addition, physicians self-rated the importance of various motivations for practicing medicine. The top six ranked mean ratings indicate that the primary motivations for practicing medicine were satisfaction derived from solving medical problems and the desire to help people. The interaction of these physician and patient characteristics is offered as a partial explanation for the development of difficult physician-patient relationships. PMID- 2913180 TI - Family physicians' perceptions of the family conference. AB - Ninety-one of 127 graduates (72 percent) of one family practice residency returned a questionnaire in which they estimated the likelihood that their patients would want a physician-family conference for each of 21 clinical situations. For each situation the physicians also rated their own preferences regarding patients' interest in family conferences. Serious medical illnesses received the highest ratings for both sets of ratings. For all 21 situations, physicians' estimates of patients' responses were significantly lower than physicians' preferred response ratings. The physicians' estimates and preferences regarding patients' interest in family conferences were compared with actual patients' ratings obtained in a previous study. The patient ratings were significantly greater than the physicians' estimates of patient ratings for 14 of 21 situations; the physicians' preferences ratings were significantly higher than the actual patient ratings for 11 situations and lower for three situations. The mean number of actual family conferences conducted in the previous month was 2.6, and 66 percent of respondents had conducted at least one such conference during this time. These data indicate that physicians may be more interested in family conferences than their patients are, but that they may underestimate the degree to which patients do, in fact, want them. The implications of these data for teaching, practice, and research are discussed. PMID- 2913181 TI - Patients' attitudes toward physician involvement in family conferences. AB - Patients' interest in family conferences was investigated using Doherty and Baird's concept of level of physician involvement with families. Patients entering two primary care clinics (N = 239) completed a questionnaire assessing their interest in physician level of involvement for each of six representative clinical situations: hospitalization for serious illness, new diagnosis of serious illness, depression, marital or relationship problems, stress-related symptoms, and frequent visits without improvement. Most patients indicated that they would want family conferences with their primary physician if a family member experienced hospitalization, new diagnosis of a serious illness, or depression. Slightly less than one half of the patients indicated that they would want family conferences for the remaining situations. Among those patients desiring family conferences, majorities responded that they would want their primary physician to provide all of Doherty and Baird's levels 2 through 5 (ongoing medical information and advice, feelings and support, systematic assessment and planned intervention, and family therapy), especially for hospitalization for serious illness and for depression. Most patients who indicated that they would want their physician to provide family therapy in the family conference also responded that they would want referral to a mental health professional for family therapy. The implications of these findings for clinical practice, residency training, and future research are discussed. PMID- 2913182 TI - Utilization of hospital services. A comparison of internal medicine and family practice. AB - Five hundred twenty new patients were randomly and prospectively assigned to receive care in the Internal Medicine Clinic or Family Practice Clinic of a large university hospital. Previous analyses of outpatient data demonstrated that the frequency of visits to the clinic of primary care, acute care clinic, emergency room, and consultant clinics were all significantly higher for patients randomized to internal medicine compared with family practice. In the present study, patients' charts were reviewed for information regarding hospitalizations. During the 3.4-year study period, there were a total of 61 hospital admissions for internal medicine (35 of 249 patients), and 58 for family practice (27 to 271 patients). Age (mean 47 years) and sex of patients in both groups were equivalent. The average total cost of hospitalization for each patient was greater for those randomized to the Internal Medicine Clinic: $7,193 for internal medicine patients as compared with $5,764 for family practice patients. The professional costs per hospitalization showed greater variation: $913 for Internal Medicine Clinic patients and $629 for Family Practice Clinic patients. Internal Medicine Clinic patients had a longer mean length of hospitalization (7.5 days) when compared with that of Family Practice Clinic patients (6.3 days). It can be concluded that in this clinical environment the hospitalization patterns are different for patients assigned to the Internal Medicine Clinic compared with the Family Practice Clinic: both cost and length of care for hospitalization are less for those followed by the Family Practice Clinic. PMID- 2913183 TI - The peer-review process--and an acknowledgement of our peerless reviewers. PMID- 2913184 TI - The post-operative electrocardiogram and creatine kinase: implications for diagnosis of myocardial infarction after non-cardiac surgery. AB - The objective of this study was to evaluate different approaches to the diagnosis of post-operative myocardial infarction. A total of 232 patients, mostly hypertensive and/or diabetic patients, who were undergoing elective non-cardiac surgery were evaluated pre-operatively. They were followed serially from the day of operation to discharge or the sixth post-operative day with daily clinical evaluations, electrocardiograms, creatine kinase and creatine kinase isoenzymes. In total 22% (51/232) of the patients had post-operative ECG changes in two or more leads. Only 1% developed new Q waves; most of the changes involved changes in the T or ST segments. Seventy percent of patients who had changes in their electrocardiogram were completely asymptomatic. The highest risk of ECG changes or symptoms occurred on the day of operation and the first post-operative day; evidence of post-operative infarction was infrequent after the second post operative day. Creatine kinase levels rose an average of 250-300 IU on the first and second post-operative day (also the peak time for post-operative ECG changes), reducing its utility as an adjunct to the diagnosis of post-operative infarctions. Importantly, 52% (12/23) of the patients who had greater than or equal to 5% MB isoenzyme had neither ECG changes nor symptoms; the diagnosis of a myocardial infarction should not be made in these patients. In summary, most patients who experience ischemia or infarction post-operatively are asymptomatic. Symptoms should not be required for the diagnosis of post-operative infarction. Seemingly minor differences in criteria can produce major discrepancies in post operative myocardial infarction rates (from 1 to 9%). The development of a final set of criteria will require further study but the diagnosis of post-operative infarction should probably be based on ECG changes, their duration and consistency, and the association of a positive MB fraction. PMID- 2913185 TI - Cause specific mortality following cerebral infarction. AB - Mortality from four causes (index stroke, subsequent stroke, cardiac disease and non-cardiovascular causes) was examined during a 5 year follow-up of 1694 cerebral infarction patients admitted to 25 community hospitals between 1969 and 1973. The hazard for mortality from the index stroke was high initially, but declined to a negligible level by 6 months post-stroke. In contrast, hazards for mortality from subsequent strokes, cardiac diseases and non-cardiovascular causes each peaked midway through the first year, declined during the remainder of that year, and then increased in the latter part of the follow-up. Proportional hazards analysis indicated that advanced age and increased stroke severity were the only factors significantly related to increased risk from each of the four causes of death. Other risk factors were significant only for one or two select causes of death. White patients were less likely to die from subsequent strokes, but more likely to die from cardiac diseases, than were non-white patients (primarily blacks). Males were more likely to die from both the index stroke and non-cardiovascular causes than females. A history of cardiac disease increased the risk of death from both the index stroke and from future cardiac events, while a history of hypertension or diabetes increased the risk of death from non cardiovascular causes, and a history of previous stroke increased the risk of death from subsequent stroke. PMID- 2913186 TI - Assessing methods for causality assessment of suspected adverse drug reactions. AB - Reproducibility and validity as currently defined are inappropriate criteria for the evaluation of methods for causality assessment. Reproducibility leads to suppression rather than resolution of real disagreements and the method used to establish validity relies on the tarnished gold standard of expert opinion. We describe six alternative criteria that attempt to address a potential user's main concerns--the need to know whether to believe the results in general and in a particular case. These criteria focus on the internal structure of a method rather than its output. When we assessed the published methods by these criteria most of the methods failed most of the criteria. We believe that the problem and its solution lie at a fundamental level--real understanding of the true nature of causality assessment, which we suggest is an inherently subjective evaluation based on the multiple uncertainties that an assessor has about a case and not an objective attribute of the drug-event connection that can be determined from unambiguous evidence elicited in response to "operational questions". PMID- 2913187 TI - Cyclical mastopathy: an evaluation of methods of assessment. AB - We have evaluated three methods of assessing patients with cyclical breast symptoms (cyclical mastopathy--CM). One method, a screening questionnaire, was used to identify women with CM, and two others, a symptom severity questionnaire and a daily diary, were used prospectively to record the severity of symptoms in relation to the menstrual cycle. The screening questionnaire was assessed for test-retest reliability and for agreement between the recalled severity of symptoms and those recorded during prospective measurement. The symptom severity questionnaire and diary were assessed by examining their ability to discriminate between pre- and postmenstrual phases of the menstrual cycle, differences in symptom severity at these times being the cardinal feature of CM. Test-retest reliability of premenstrual symptoms by the screening questionnaire gave correlation coefficients over 0.70 for 9 of the 11 items assessed. The symptom severity questionnaire showed significant differences between pre- and post menstrual scores for 8 of the 11 items assessed and the diary for each of the 2 items assessed. Comparison of symptom severity as recalled and as prospectively recorded showed only modest agreement. These results show that the instruments used to assess symptom severity performed satisfactorily but that the screening questionnaire used to identify women with CM, although reliable, correlated only moderately well with prospective measurement. PMID- 2913188 TI - Alcohol consumption and mortality in aging or aged Finnish men. AB - The association between alcohol consumption and 10-year mortality by death cause was studied in 1112 men aged 55-74 years and living either in eastern or south western Finland. After adjustment for age, blood pressure, smoking, serum cholesterol, and other variables, the relative odds ratio of 10-year total mortality associated with consuming 1-273 g of absolute alcohol per month was 0.9 (95% confidence interval of 0.6-1.2) and with consuming more than 273 g per month due to violence was small, 15, but relative odds of violent death associated with consuming 1-273 and 274 or more grams of alcohol per month were 3.4 and 16.2, respectively (95% confidence intervals of 0.4-31.9 and 1.9-141.2). PMID- 2913189 TI - Reliability and validity of screening scales: effect of reducing scale length. AB - Self-report measures are often useful as the first phase of a multiphase case identification procedure for estimating rates of untreated disorder, but such measures are susceptible to several sources of unreliability. The reliability of respondents' reports can be greatly improved by employing a well-established screening scale composed of multiple replicate items. A practical question that arises is whether interview time can be saved by using only a portion of the original scale. The cost of shortening established scales in terms of the sensitivity and specificity of the screen is modelled statistically, and the robustness of the model is assessed using mental health data obtained on samples of psychiatric patients and community controls. Both the statistical model and the empirical examples suggest that items from highly reliable measures can be dropped without much loss in sensitivity or specificity. Suggestions are made for selecting subsets of items when shortening a screening scale and these are illustrated with screening scales for depression. PMID- 2913190 TI - Public and private hypotheses. AB - The uses of hypothesis in scientific medicine and in clinical medicine are broadly similar; but they differ in subtle but important logical details. The key distinction is that scientific medicine deals with broad ("public") hypotheses about entire populations; and the predominant problem of inference is statistics in the face of epistemological uncertainty. In contrast, clinical medicine deals with individual, tailor-made ("private") hypotheses; the uncertainty (e.g. the diagnosis or recurrence risk in relatives) is ontological, and the main feature of the analysis is probability. The same logical rules are at times mistakenly applied to both. Disregard of these subtleties may lead to paradoxes, contradictions, and at times diastrously false conclusion. The basic principles and distinctions are laid out with illustrations that are most readily provided from medical genetics, but apply to all branches of medicine. PMID- 2913191 TI - Hectic families. PMID- 2913193 TI - Quality of life and cardiac disease. PMID- 2913192 TI - Plasma cholesterol and in situ cervical cancer: an Australian case-control study. PMID- 2913194 TI - Quality of life of elderly patients enrolled in cardiac rehabilitation. AB - The quality of life of 51 elderly subjects enrolled in cardiac rehabilitation is described to devise strategies for improving QOL as an outcome of a therapeutic regimen. Based on Chrisman and Fowler's Systems-in-Change Model, physical function, social function, and emotional function were assessed via the McMaster Health Index Questionnaire and the Cantril Self-Anchoring Scale during participation in cardiac rehabilitation. The greatest benefit of cardiac rehabilitation to subjects was in physical function, but benefits were also noted in social and emotional function. PMID- 2913195 TI - Life-style changes in a cardiac rehabilitation program: the client perspective. AB - Major life-style changes are required after an acute coronary event, although the vast majority of patients are unsuccessful in maintaining these changes. This study examines factors clients view as enabling or disabling their life-style changes for health promotion. Ten patients in a cardiac rehabilitation program were interviewed using grounded theory methodology. Both health protection and health promotion stimulated life-style change, as did instructions from the physician and life enjoyment. Enabling and disabling factors affecting the process of repatterning were individually defined, but changes in beliefs, attitudes, and plans facilitated repatterning. Specific precipitants to change, forces influencing change, and methods of repatterning life style are discussed, as are nursing implications. PMID- 2913196 TI - Nursing research. The use of grounded theory methodology to study the process of life-style changes. AB - This article describes a method of evaluating research with the use of grounded theory methology, a qualitative research technique. The preceding article by Frenn and colleagues, which uses this method to study the process of life-style change, is evaluated as an example. Sample procedures, data collection and analysis, and evaluation of scientific merit are discussed. PMID- 2913197 TI - Congenital heart diseases in adults. Nursing grand rounds. AB - Diagnosis of significant disease is a major stressor that may interfere with a patient's quality of life. This case study reports the nursing care of a 29-year old female marathon runner diagnosed with congenital heart disease. The nursing diagnoses, Alteration in Family Process, Disturbance in Self-Esteem, and Knowledge Deficit are addressed in care plan format. PMID- 2913198 TI - Angiotensin converting enzyme inhibitors. AB - The angiotensin converting enzyme inhibitors are beneficial to hypertensive patients and those experiencing congestive heart failure. These agents appear to have fewer side effects than many other commonly used agents. Nursing interventions include monitoring for individual responses to the drugs and providing adequate education to ensure the patient's compliance with the drug regime. PMID- 2913199 TI - Determinants of patchy metabolic labeling in the somatosensory cortex of cats: a possible role for intrinsic inhibitory circuitry. AB - Despite repeated experimental demonstration that somatic stimulation leads to an intermittent, "column-like" pattern of 2-deoxyglucose (2DG) label in the somatosensory cortex, the functional significance of this pattern remains uncertain. A number of recent studies have suggested that the putative inhibitory neurotransmitter GABA may play an influential role in the cortical processing of sensory information. To test the possibility that GABA-mediated inhibitory processes might participate in the formation of the 2DG patches, the 2DG pattern obtained under "normal" experimental conditions was compared with the pattern observed when cortical inhibition was modified by topical application of the GABA antagonist, bicuculline methiodide (BIC). Under "normal" experimental conditions, we found that somatic stimulation led to an intermittent, patch like distribution of 2DG uptake in cat somatosensory cortex, which exhibited consistent features in animals studied using the same stimulus and experimental condition. Reconstructions of the stimulus-evoked activity patterns revealed that the label was confined to territories known to receive input from the stimulated body region and was organized into elongated strips. Topical application of BIC to the somatosensory cortex dramatically altered the dimension of the metabolic patches, which were often embedded in a field of elevated 2DG uptake. In BIC-treated hemispheres the average width of 2DG patches was 1266 microns, whereas the average width of patches in the opposite untreated hemisphere (elicited by identical stimuli) was 713 microns. Unfolded maps of the labeling pattern revealed that in the BIC-treated hemispheres adjacent "strips" of 2DG label tended to fuse, leading to a less intermittent distribution than that observed in the untreated hemispheres. An important role for GABA in the formation of the normal cortical response to somatic stimulation is suggested. PMID- 2913200 TI - The role of preparation in tuning anticipatory and reflex responses during catching. AB - The pattern of muscle responses associated with catching a ball in the presence of vision was investigated by independently varying the height of the drop and the mass of the ball. It was found that the anticipatory EMG responses comprised early and late components. The early components were produced at a roughly constant latency (about 130 msec) from the time of ball release. Their mean amplitude decreased with increasing height of fall. Late components represented the major build-up of muscle activity preceding the ball's impact and were accompanied by limb flexion. Their onset time was roughly constant (about 100 msec) with respect to the time of impact (except in wrist extensors). This indicates that the timing of these responses was based on an accurate estimate of the instantaneous values of the time-to-contact (time remaining before impact). The mean amplitude of the late anticipatory responses increased linearly with the expected momentum of the ball at impact. The reflex responses evoked by the ball's impact consisted in a short-latency coactivation of flexor and extensor muscles at the elbow and wrist joints. Their mean amplitude generally increased with the intensity of the perturbation both in the stretched muscles and in the shortening muscles. We argue that both the anticipatory and the reflex coactivation are centrally preset in preparation for catching and are instrumental for stabilizing limb posture after impact. A model with linear, time varying viscoelastic coefficients was used to assess the neural and mechanical contributions to the damping of limb oscillations induced by the ball's impact. The model demonstrates that (1) anticipatory muscle stiffening and anticipatory flexion of the limb are synergistic in building up resistance of the hand to vertical displacement and (2) the reflex coactivation produces a further increment of hand stiffness and viscosity which tends to offset the decrement which would result from the limb extension produced by the impact. PMID- 2913201 TI - Adaptation to suppression of visual information during catching. AB - We address the problem of whether and how adaptation to suppression of visual information occurs in catching behavior. To this end, subjects were provided with advance information about the height of fall and the mass of a ball and an auditory cue signaled the time of release. Adaptation did occur, as indicated by the unimpaired ability to catch the ball without vision; however, it involved a major reorganization of the muscle responses. The subjects were unable to produce anticipatory activity consistently, but preset the responses elicited by the impact. These responses were more complex and prolonged than those observed in the control experiments (with vision). In particular, medium- and long-latency responses were much larger, and the changes in elbow, wrist, and metacarpophalangeal angles following impact were more oscillatory than in the control. The general pattern of the EMG responses switched from that characteristic of catching with vision to that characteristic of catching without vision from the first trial of each experiment. However, the responses produced without vision were calibrated adaptively in the course of an experiment. In fact, the limb oscillations induced by the impact were significantly larger in the first trial than in the following trials. This seems to suggest that the parameters of the responses are adjusted based on an internal model of the dynamic interaction between the falling ball and the limb. This model is initially constructed from a priori knowledge on impact parameters and is subsequently updated on the basis of the kinesthetic and cutaneous information obtained during the first trial. PMID- 2913202 TI - Expression of nerve-muscle topography during development. AB - Previous studies have indicated that in 2 muscles of the adult rat, the anterior serratus and the diaphragm, the rostrocaudal axis of the motoneuron pool projects topographically onto the rostrocaudal axis of the muscle. In the present work we have asked whether this orderly topography emerges as a function of postnatal synaptic rearrangement or whether this pattern is already established at birth. The anterior serratus muscle was studied over the period ranging from embryonic day 17 through postnatal day 30. Using 2 criteria of topography, average segmental innervation and average target field of cervical roots C6 and C7, we found that a topographic distribution of the motoneuron pool is already present prior to birth and maintained throughout the postnatal period. Moreover, both C6 and C7 form an orderly map over the surface of the serratus in the embryo, and the topography is sharpened during postnatal periods. The diaphragm also is topographically innervated at birth and undergoes a comparable sharpening of the projection map postnatally. We conclude that the topographic projection of motoneurons is established prior to birth in these muscles, and postnatal synaptic rearrangement serves to sharpen the topographic map toward the adult pattern. These results also suggest that the pursuit of basic mechanisms underlying topography should be directed toward initial embryonic nerve-muscle contacts. PMID- 2913203 TI - Topographical organization of the entorhinal projection to the dentate gyrus of the monkey. AB - The topographic organization of the projections from the entorhinal cortex to the dentate gyrus in the macaque monkey was studied with anterograde and retrograde tracing methods. Injections of WGA-HRP or the fluorescent retrograde tracers, Fast blue and Diamidino yellow, were placed at various levels along the rostrocaudal axis of the dentate gyrus and hippocampus. In 5 experiments the fluorescent dyes were injected at 2 rostrocaudal levels of the same dentate gyrus. Labeled neurons were observed mainly in layers II and III of the entorhinal cortex, though some were also seen in layers V and VI. The labeled layer II cells resulting from each of the tracer injections were located throughout much of the rostrocaudal extent of the entorhinal cortex, though they tended to have a more limited distribution in the transverse or mediolateral axis. Injections of retrograde tracers located caudally in the dentate gyrus resulted in a rostrocaudally oriented zone of labeled cells that was situated laterally in the entorhinal cortex adjacent to the rhinal sulcus. The zone of labeled cells was not oriented strictly parallel to the rhinal sulcus since at caudal levels it extended medially to encompass the full transverse extent of the most caudal portion of the entorhinal cortex. When injections were placed more rostrally in the dentate gyrus and hippocampus, the rostrocaudally oriented zone of labeled cells was situated more medially in the entorhinal cortex. Anterograde tracing experiments using 3H-amino acid injections into different rostrocaudal and mediolateral positions of the entorhinal cortex confirmed the organization demonstrated by the retrograde tracers and further indicated that the entorhinal fibers terminate in the outer two-thirds of the molecular layer of the dentate gyrus. Unlike in the rat, where the entorhinal termination zone in the molecular layer is clearly bilaminate, projections from all portions of the entorhinal cortex appeared to terminate more diffusely throughout the outer two-thirds of the molecular layer. The results of the present study indicate that rostrocaudally oriented zones of cells that cut across several cytoarchitectonic subdivisions of the entorhinal cortex give rise to topographically organized projections to the dentate gyrus. Cells located laterally in the entorhinal cortex project to caudal levels of the dentate gyrus, whereas progressively more medially situated cells project to progressively more rostral parts of the dentate gyrus. PMID- 2913204 TI - The role of gonadal hormones in neuromuscular synapse elimination in rats. I. Androgen delays the loss of multiple innervation in the levator ani muscle. AB - The normal period of synapse elimination in the androgen-sensitive levator ani (LA) muscle occurs between 2 and 4 weeks after birth, well after the period of synapse elimination for most other rat muscles. To evaluate whether gonadal androgen might be involved in the delayed development of single innervation in the LA, we compared the time course of synapse elimination in LA muscles that lacked endogenous gonadal androgen or were exposed to exogenous androgen. Tetranitroblue tetrazolium was used to stain neuromuscular connections. Our results suggest that both endogenous and exogenous androgen delay the normal process of synapse elimination. Removing endogenous androgen resulted in lower levels of multiple innervation in the LA, suggesting that androgen may normally influence synapse elimination. Moreover, androgen treatment prevented much of the normal loss of multiple innervation in the LA. Androgen treatment during the normal period of synapse elimination also increased the diameter of LA muscle fibers, enhanced the development of preterminal branching, and increased the number of junctional sites on some LA fibers. Because androgen did not appear to induce the formation of new synapses through sprouting, we conclude that androgen maintained multiple innervation in the LA by preventing the normal ontogenetic process of synapse elimination. PMID- 2913205 TI - The role of gonadal hormones in neuromuscular synapse elimination in rats. II. Multiple innervation persists in the adult levator ani muscle after juvenile androgen treatment. AB - In the previous study (Jordan et al., 1989), we demonstrated that androgen treatment of juvenile male rats inhibits the elimination of synapses in the levator ani (LA) muscle. In the present study, we asked whether synapse elimination would occur once this juvenile androgen treatment ended. Castrated male rats were given androgen during a juvenile treatment period (7-34 d) and were killed 4 or 8 weeks after the end of androgen treatment (at 9 or 13 weeks after birth). The adult pattern of innervation in the LA was assessed (1) anatomically by counting the number of stained motor axons innervating single muscle fibers and (2) electrophysiologically by counting the number of components in intracellularly recorded endplate potentials. Based on the number of stained motor axons, the LA from juvenile androgen-treated castrates had as much multiple innervation 1 and 2 months after the end of androgen treatment (at 9 and 13 weeks) as was present during androgen treatment at 4 weeks. This suggests that no further synapse loss occurred in the LA once androgen treatment ended. Based on electrophysiological measures, adult LA muscles previously exposed to androgen were found to contain significantly more polyneuronal innervation than normal adult LA muscles. Juvenile androgen treatment also increased the size but not the number of motoneurons in the spinal nucleus of the bulbocavernosus which contains LA motoneurons. Thus, the increased level of multiple innervation in the LA is not due to a higher than normal number of motoneurons innervating this muscle. Because multiple innervation persists in the LA in the absence of continued androgen treatment, androgen may have permanently prevented synapse elimination.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2913206 TI - Structural and functional properties of reticulospinal neurons in the early swimming stage Xenopus embryo. AB - This study presents direct evidence that in Xenopus laevis embryos ipsi- and contralaterally descending reticulospinal fibers from the caudal brain stem project to the spinal cord, where they directly contact primary motoneurons. At stage 30, occasional contacts between primary motoneurons and descending axons are present. These contacts are possibly already functional since presynaptic vesicles were sometimes observed. Furthermore, the physiological data obtained in this study suggest that reticulospinal neurons in the caudal brain stem are involved in the central generation of early swimming. The first ingrowth of reticulospinal axons was observed in the rostral spinal cord after application of HRP to the caudal brain stem of stage 27/28 embryos. By stage 32, many supraspinal axons could be found in the spinal cord at the level of the 12/13th myotome, near the time of the first rhythmic swimming. Both lamellipodial and varicose growth cones were found. Intracellular recordings from the brain stem and extracellular recordings from the myotomal muscles in curarized embryos around stage 30 revealed neurons in the caudal brain stem which were active during early fictive swimming. After intracellular staining with Lucifer yellow neurons with descending axons were found in the brain-stem reticular formation. These reticulospinal neurons showed "motoneuron-like" phasic activity, producing one spike each swimming cycle. Rhythmically occurring spikes with swimming periodicity were superimposed on a sustained depolarization level of some 5-30 mV. Reticulospinal neurons in the brain stem resemble descending interneurons in the spinal cord by their morphology, projection pattern, and activity during early swimming. Reticulospinal neurons and descending interneurons might therefore form one continuous population of projecting interneurons with a different location but a similar function. In support of this we propose that the embryonic brain-stem reticular formation forms part of the swimming pattern generator. PMID- 2913207 TI - Responses of lateral geniculate neurons that survive long-term visual cortex damage in kittens and adult cats. AB - Damage to visual cortex (areas 17-19) in kittens or adult cats produces severe retrograde degeneration of neurons in the dorsal lateral geniculate nucleus (LGN). However, some neurons survive in otherwise degenerated portions of the LGN after a visual cortex lesion at any age. Previous studies have shown that there are well-defined differences in potential retinal inputs, soma size, synaptic connections, outputs, and physiological properties of output targets of the surviving LGN cells in cats that received visual cortex damage at different ages. The present experiment investigated the relationships between these differences and the responses of surviving LGN neurons to visual stimulation. Recordings were made from surviving neurons in the degenerated A- and C-layers of the LGN in cats that had received a visual cortex lesion on the day of birth, at 8 weeks of age, or as adults (survival was 11.5-36 months). Normal adult cats were studied for comparison. The visual receptive field was mapped, and tests were carried out to classify each cell as X, Y, or W. In addition, quantitative methods were used to assess response amplitude, strength of receptive-field surround inhibition, spatial-frequency tuning to drifting or counterphased sine-wave gratings, and response to nondominant-eye stimulation for each cell. We found that surviving cells in all LGN layers respond to light, have normal receptive-field organization, and have normal eye dominance following a lesion at any age tested. In addition, gross retinotopic organization of the LGN is normal. However, 2 main abnormalities were observed following a lesion at all 3 ages. First, there is a reduction in the percentage of X cells in the A layers, from 62% in normal LGNs to about 15% in degenerated LGNs. Second, many surviving cells in both the A- and C-layers have abnormally large receptive-field centers. Other differences that were observed between normal A-layer cells and surviving A-layer cells could be attributed to the loss of X cells. These results indicate that cells within a structure that shows severe retrograde degeneration after brain damage can maintain relatively normal function and can take part in potentially important residual neural pathways. Previous studies indicate that these residual pathways can show both anatomical and physiological compensation for the brain damage, and the present findings bear on the consequences and mechanisms of this compensation. PMID- 2913208 TI - Cerebellar lesions and the nictitating membrane reflex: performance deficits of the conditioned and unconditioned response. AB - Unilateral cerebellar lesions abolished the occurrence of ipsilateral conditioned nictitating membrane responses during the 285 msec interval between onset of the conditioned and unconditioned stimuli on paired trials. This effect was obtained in 15 animals sustaining damage to the dorsolateral aspects of the interpositus nucleus and the adjoining white matter. However, conditioned responses did occur during the 800 msec observation interval employed on tone-alone test trials, and these responses exhibited the classic performance deficits normally associated with cerebellar damage: a low frequency of occurrence (14%, as compared with 96% before the lesion); a 3.1 mm decrease in amplitude; a 236 msec increase in onset latency; a 563 msec increase in latency of peak amplitude; and a 327 msec increase in rise time. Four of the 15 animals failed to demonstrate greater than 5% responding during the test trials. These performance deficits were not specific to the learned, conditioned response. Unconditioned responses were also reduced in frequency and increased in latency of peak amplitude and rise time, especially when elicited at lower air-puff intensities. These deficits in the unconditioned response were observed in animals that failed to exhibit conditioned responses on either paired or test trials, as well as in animals demonstrating conditioned responses only during test trials. We conclude that the cerebellum has a general role in regulating the nictitating membrane reflex so that deficits in learned responses observed after cerebellar lesions are secondary to a broader deficit in performance. The performance deficits appear to consist of a sensory component, as reflected by an increase in stimulus threshold for elicitation of the nictitating membrane reflex, and a motor component, as reflected by the altered topography of the evoked response. The results of this study thus reaffirm the role of the cerebellum in regulating the sensorimotor processes necessary for the optimal performance of both conditioned and unconditioned responses and extends this role to the expression of a simple cranial nerve reflex. PMID- 2913209 TI - Sequence of pedal peptide: a novel neuropeptide from the central nervous system of Aplysia. AB - We report the identification of a novel neuropeptide from Aplysia nervous tissue. The peptide was termed Pedal peptide (Pep) because it was predominantly synthesized in the pedal ganglia. Pep was purified and sequenced from pooled extracts of pedal ganglia. The following sequence was proposed: Pro-Leu-Asp-Ser Val-Tyr-Gly-Thr-His-Gly-Met-Ser-Gly-Phe-Ala. Enzymatic hydrolysis procedures indicated that Pep had a free carboxyl terminal. A peptide with the proposed sequence was synthesized and compared with the native peptide. Chromatographic properties of the 2 peptides under 3 different conditioned were compared and found to be identical. Electrophysiological responses to the 2 peptides were compared on an identified neuron in the abdominal ganglia and found to be qualitatively and quantitatively very similar. Both peptides produced net inward currents that were associated with a decrease in membrane conductance. The results from these 2 procedures confirmed that the proposed Pep sequence was correct. Quantitative measurements of the incorporation of 35S-methionine into Pep suggest that cell bodies that synthesize Pep were present predominantly in the pedal ganglia but should also be found in other central ganglia as well. Pep like immunoreactive neurons are found predominantly in the pedal ganglia and less frequently in the other ganglia (Pearson and Lloyd, 1989). Quantitatively, Pep constitutes one of the predominant peptides in the nervous system of Aplysia. Pep does not appear to be a member of any other previously identified invertebrate or vertebrate peptide family. PMID- 2913210 TI - Immunocytological localization of pedal peptide in the central nervous system and periphery of Aplysia. AB - Immunocytology using antisera raised to conjugated pedal peptide (Pep) was used to localize the peptide in the CNS and periphery of Aplysia. A total of over 200 neurons in the CNS exhibited Pep-like immunoreactivity. As expected from results presented in the previous paper, immunoreactive neurons were heavily concentrated in the pedal ganglia, primarily in a broad ribbon comprised of about 60 large contiguous neurons on the dorsal side of each ganglion. Smaller and less numerous immunoreactive neurons were found in the other ganglia. A number of neurons primarily located in the abdominal ganglia had dense networks of immunoreactive varicose fibers surrounding their cell bodies. Many immunoreactive axons were observed in peripheral nerves, particularly those nerves leaving the pedal ganglia. Analyses of sections of body wall indicated that Pep-like immunoreactivity was localized to a series of varicose axons that appeared to be associated with vascular spaces, muscle fibers, and other large cells. These axons likely arise from pedal ganglion nerves that were shown to transport large amounts of 35S-labeled Pep to the periphery. These results suggest that Pep is a transmitter-like neuropeptide that is likely to have a number of important physiological actions in Aplysia. PMID- 2913211 TI - Visual receptive fields in the striate-recipient zone of the lateral posterior pulvinar complex. AB - The lateral posterior (LP)-pulvinar complex of the cat is known to contain multiple visual areas. In the present study, we examined the receptive field properties of single neurons isolated in the lateral division of this complex (the LPI). The LPI is designated the striate-recipient zone because it is the only region of the LP-pulvinar receiving cortical projections from areas 17 and 18. The recordings revealed that the striate-recipient zone of LP comprises 2 subareas, which we have termed LPI-1 and LPI-2. In the main segment (LPI-1), virtually all cells responded securely to visual stimuli. The vast majority of these neurons were binocular, with relatively small and well-defined receptive fields. More than half of the cells were found to be directionally selective, and almost this many were orientation specific. The orientation tuning of these cells was found to be quite precise, comparable to complex cells in area 17. In contrast, in the small dorsolateral segment of the striate-recipient zone (the LPI-2), a substantial proportion of cells could not be visually activated. Here, the visual cells had very large receptive fields, and relatively few were direction or orientation selective. The LPI-2 receives subcortical inputs from the superficial layers of the superior colliculus, the hypothalamus, and cerebellum, while the LPI-1 is innervated only by cortical axons. It is suggested that the subcortical connections of the LPI-2 account for the differences in the response properties of the 2 striate-recipient areas. The present results, in conjunction with our previous findings on the principal tectorecipient zone (Chalupa et al., 1983), permit 2 generalizations regarding the functional organization of the cat's LP-pulvinar complex. First, there are clear differences among the visual areas of the LP-pulvinar in the cellular processing of visual information. Second, these functional differences can be related to the principal sources of visual input to the various divisions of the LP-pulvinar. PMID- 2913212 TI - Aplysia synaptosomes. I. Preparation and biochemical and morphological characterization of subcellular membrane fractions. AB - We prepared and characterized subcellular membrane fractions from the CNS of Aplysia californica that are enriched in isolated nerve terminals (synaptosomes). Ganglia were homogenized in 1.1 M sucrose and fractionated on a 2-step sucrose gradient, yielding 50 micrograms protein/animal in the synaptosomal fraction (P3), which was enriched 3-fold in plasma membrane as compared with the initial homogenate. Quantitative morphometry of electron micrographs revealed that P3 contained 25% intact synaptosomes, a 5-fold enrichment over the homogenate. Although fractionation on a 5-step sucrose gradient reduced the yield of protein in the synaptosomal fraction to 40 micrograms/animal, this fraction (the 0.35 M/0.75 M interface) was more enriched in plasma membrane than P3 and was less contaminated by lysosomes and free mitochondria. By electron microscopy, the 0.35 M/0.75 M interface contained up to 50% synaptosomes. Synaptosomal fractions contained cAMP-, Ca2+/calmodulin-, and Ca2+/phospholipid-dependent protein kinase activities and were enriched in a Mr 40,000 pertussis toxin substrate, Gi/o. In the accompanying paper, we show that these synaptosomes retain the ability to release transmitters. PMID- 2913213 TI - Habituation and dishabituation of a cleaning reflex in normal and mutant Drosophila. AB - Upon tactile stimulation of its thoracic bristle(s), Drosophila cleans with a patterned set of leg movements the field covered by the stimulated bristles. We demonstrate that this cleaning reflex undergoes habituation and dishabituation. Repeated monotonous stimulation of the bristles by controlled air puffs leads to decrement, and finally to disappearance, of leg response. Spontaneous recovery of the response takes place in a time-dependent manner. Restoration of response can also be obtained by application of a high-frequency stimulus directed to other bristles. A mutant, rut, which is defective in learning and in adenylate cyclase activity, can habituate and dishabituate, but habituation is abnormally short lived. As opposed to both nonassociative and associative learning paradigms used in Drosophila to date, the cleaning reflex lends itself to some aspects of cellular analysis, since single sensory neurons that mediate the input and motor neurons that mediate the behavioral output are identifiable. The modified reflex should therefore be useful in establishing the effects of single gene mutations that affect behavioral plasticity on the development and properties of identified neurons that contribute to discrete modifiable behaviors. PMID- 2913214 TI - Cranial vault growth in craniosynostosis. AB - Skull growth after single suture closure was described in 1851 by Virchow, who noted that growth in the plane perpendicular to a fused suture was restricted. However, this observation failed to predict compensatory growth patterns that produce many of the deformities recognized as features of individual syndromes. The deformities resulting from premature closure of a coronal, sagittal, metopic, or lambdoid suture can be predicted on the basis of the following observations: 1) cranial vault bones that are prematurely fused secondary to single suture closure act as a single bone plate with decreased growth potential; 2) asymmetrical bone deposition occurs mainly at perimeter sutures, with increased bone deposition directed away from the bone plate; 3) sutures adjacent to the prematurely fused suture compensate in growth more than those sutures not contiguous with the closed suture; and 4) enhanced symmetrical bone deposition occurs along both sides of a non-perimeter suture that is a continuation of the prematurely closed suture. These observations regarding growth in craniosynostosis are illustrated with clinical material in this report. PMID- 2913215 TI - Civilian gunshot wounds to the brachial plexus. AB - Many gunshot wounds (GSW's) to the brachial plexus do not improve spontaneously with time and are therefore candidates for surgery. Over an 18-year period, 141 patients with GSW's were evaluated, 90 of whom were operated on; 75 of the surgical cases were followed for 2 years or more. Thirty operative patients had initial vascular repair, while eight required thoracotomies. Total plexus palsy was present in 19 of those selected for operation. The average interval between injury and operation was 17 weeks. Six patients required early operation for an expanding aneurysm with progressive neural loss. Persistent complete loss of function in the distribution of one or more elements and/or noncausalgic pain not managed by medications provided the major operative indications. Four patients required sympathectomies for causalgia. Of 166 lesions in continuity believed to be complete, based on clinical examination and electromyography, 48 with preserved intraoperative nerve action potentials (NAP's) were spared resection or were treated with a split repair with excellent eventual results on a weighted grading system. By comparison, only seven of 55 elements believed to have incomplete loss or to be recovering did not have NAP's and required repair. Fifty three of 98 lesions repaired by grafts and 18 of 26 wounds with suture repair recovered to a Grade 3 level or better. Most elements were in continuity but 14 were found "blown apart" and required repair, usually by grafting. The best outcome was achieved with upper trunk and lateral and posterior cord lesions, but recovery occurred with some C-7 to middle trunk and medial cord to median repairs. Results with lower trunk and most medial cord lesions were poor unless early regeneration was proved by operative NAP's, in which case either neurolysis or split repair could be performed. Surgery is warranted for selected GSW's to the plexus. PMID- 2913216 TI - Polyol content of cerebrospinal fluid in brain-tumor patients. AB - In order to investigate whether cerebrospinal fluid (CSF) polyols are consumed by brain tissue, the concentration of seven polyols in the CSF and the serum of 30 patients with intracranial tumor and 17 control individuals was measured by gas chromatography. The mean polyol content in the control samples showed that the fructose, inositol, and glucitol levels were significantly greater in CSF than in serum. A comparison of the lumbar CSF from control subjects and 11 patients with malignant tumors exposed to the CSF showed the fructose and inositol levels to be significantly lower (54% and 45%, respectively) and the glucose content to be slightly higher (110%) in the tumor cases. These differences were markedly greater in the ventricular than in the lumbar CSF and greater in patients with tumors exposed to the CSF space than in those with tumors buried in the brain tissue. In ventricular CSF obtained from seven patients with malignant brain tumors before and after radio- and/or chemotherapy, significant increases in fructose (34%) and glucitol (48%) levels were found, but the other polyols did not change significantly. In culture, the human glioblastoma cell growth rate was higher in the medium containing fructose and glucose than in that containing glucose alone. A notable amount of fructose and glucose was consumed by cultured glioblastoma cells. The roles of polyols contained in CSF and the effects of fructose on the growth of cultured glioblastoma cells are discussed in light of these findings and of previous reports. PMID- 2913217 TI - High-dose methotrexate for non-AIDS primary central nervous system lymphoma. Report of 13 cases. AB - Thirteen patients with primary lymphoma of the central nervous system (CNS) were treated with high-dose intravenous methotrexate (MTX), 3.5 gm/sq m, followed by calcium leucovorin rescue, at 3-week intervals, for three cycles. Eleven patients subsequently received radiation therapy to the whole brain, 30 to 44 Gy. Before radiation therapy, eight patients responded completely and four partially; there was one non-responder. The median Karnofsky score before high-dose MTX therapy was 60 and increased to 90 after treatment. Five of the eight complete responders reached a Karnofsky rating of 100. The three longest responders (one of whom received MTX only) were without recurrence of their disease at 29+, 32, and 32+ months posttherapy. The median response period is 9+ months. The median survival time from the date of the first MTX treatment is 9+ months, and the three longest survival times are 29+, 32+, and 54+ months. All patients received corticosteroids in either unchanging or diminishing dosages during therapy. It is concluded that primary CNS lymphoma is sensitive to high-dose MTX, which provides a safe and easily administered adjuvant to radiation therapy for this neoplasm. PMID- 2913218 TI - Administration of intravenous urea and normal saline for the treatment of hyponatremia in neurosurgical patients. AB - Hyponatremia frequently complicates the care of neurosurgical patients and requires prompt effective therapy. These patients commonly fulfill the laboratory criteria of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) or cerebral salt wasting; the classification depends on the volume status of the patient. The authors have been dissatisfied with the standard therapy of fluid restriction for the critically ill neurosurgical patient because of 1) slow rates of sodium correction; 2) poor applicability in patients requiring multiple intravenous medications and/or nutritional support; and 3) possible dangers of inducing or enhancing cerebral ischemia in patients who already may be fluid depleted. Reported successes in the treatment of hyponatremia due to SIADH by administration of urea and normal saline led to the authors' routine use of this therapy for hyponatremic neurosurgical patients. A retrospective review of an 18 month period revealed 48 patients (3% of all neurosurgical inpatients) with hyponatremia from various causes who received 62 treatments of urea and normal saline. Treatment consisted of 40 gm urea dissolved in 100 to 150 ml normal saline as an intravenous drip every 8 hours and an intravenous infusion of normal saline at 60 to 100 ml/hr for 1 to 2 days. The mean pretreatment serum sodium level (+/- standard deviation) was 130 +/- 3 mmol/liter (range from 119 to 134 mmol/liter). There was a significant mean posttreatment elevation to 138 +/- 4 mmol/liter (range 129 to 148 mmol/liter) (p less than 0.001, Student's t-test). Average daily fluid intake and output on treatment days were 2719 +/- 912 and 2892 +/- 1357 ml, respectively. There were no treatment complications in this group. It is concluded that urea and saline administration results in a rapid, safe, and effective correction of hyponatremia, making this method superior to fluid restriction in many neurosurgical patients. PMID- 2913219 TI - Polytetrafluoroethylene interposition grafts in vertebral to carotid artery transposition. A long-term follow-up study. AB - Eight patients undergoing an end-to-side vertebral artery (VA) to common carotid artery transposition between August, 1979, and July, 1982, had a polytetrafluoroethylene (PTFE) interposition graft placed when a direct anastomosis was believed not to be satisfactory. Five of these patients are living; clinical and radiographic follow-up studies over periods ranging between 54 and 82 months show that their transpositions are patent. Two patients died perioperatively, one from an acute anterior myocardial infarction and the other from acute VA occlusion with a propagating thrombus. A third patient died of myocardial infarction 20 months after graft placement; the anastomosis had been found patent at 12 months. This report gives the clinical and radiographic follow up results in a previously reported group of patients with PTFE interposition grafts. Some of these patients have been followed for over 6 years after surgery: the average radiographic follow-up period in the five survivors is 60 months, and all grafts are patent without evidence of progressive stenosis. Expanded PTFE appears to be an acceptable material for short interposition grafts in operations involving the VA; however, direct artery-to-artery anastomosis is preferred. The results of longer PTFE grafts in reconstructive cerebrovascular surgery have not been adequately studied. PMID- 2913220 TI - Carotid cave aneurysms of the internal carotid artery. AB - In a series of 32 surgical cases of carotid-ophthalmic artery aneurysm, seven of the lesions were located in the "carotid cave." This special type of aneurysm is usually small and projects medially on the anteroposterior view of the angiogram. At surgery, it is located intradurally at the dural penetration of the internal carotid artery (ICA) on the ventromedial side, appears to be buried in the dural pouch (carotid cave), and is often difficult to find, dissect, and clip. The aneurysm extends into the cavernous sinus space, and the parent ICA penetrates the dural ring obliquely. An ipsilateral pterional approach was used in all 32 cases, and ring clips were used exclusively because the aneurysms were located ventromedially. Clipping was successful in five cases. All patients returned to their preoperative occupation, although vision worsened postoperatively in two cases. The technical steps required for successful obliteration of this aneurysm are summarized as follows: 1) exposure of the cervical ICA; 2) unroofing of the optic canal and removal of the anterior clinoid process; 3) exploration of the ICA around the dural ring and opening of the cavernous sinus; 4) direct retraction of the ICA and optic nerve; and 5) application of multiple ring clips to conform to the natural curvature of the carotid artery; a curved-blade ring clip is especially useful. The relevant topographic anatomy is discussed. PMID- 2913221 TI - Cerebral arteriovenous oxygen difference as an estimate of cerebral blood flow in comatose patients. AB - The hypothesis that cerebral arteriovenous difference of oxygen content (AVDO2) can be used to predict cerebral blood flow (CBF) was tested in patients who were comatose due to head injury, subarachnoid hemorrhage, or cerebrovascular disease. In 51 patients CBF was measured daily for 3 to 5 days, and in 49 patients CBF was measured every 8 hours for 5 to 10 days after injury. In the latter group of patients, when a low CBF (less than or equal to 0.2 ml/gm/min) or an increased level of cerebral lactate production (CMRL) (less than or equal to -0.06 mumol/gm/min) was encountered, therapy was instituted to increase CBF, and measurements of CBF, AVDO2, and arteriovenous difference of lactate content (AVDL) were repeated. When data from all patients were analyzed, including those with cerebral ischemia and those without, AVDO2 had only a modest correlation with CBF (r = -0.24 in 578 measurements, p less than 0.01). When patients with ischemia, indicated by an increased CMRL, were excluded from the analysis, CBF and AVDO2 had a much improved correlation (r = -0.74 in 313 measurements, p less than 0.01). Most patients with a very low CBF would have been misclassified as having a normal or increased CBF based on the AVDO2 alone. However, when measurements of AVDO2 were supplemented with AVDL, four distinct CBF patterns could be distinguished. Patients with an ischemia/infarction pattern typically had a lactate-oxygen index (LOI = -AVDL/AVDO2) of 0.08 or greater and a variable AVDO2. The three nonischemic CBF patterns had an LOI of less than 0.08, and could be classified according to the AVDO2. Patients with a normal CBF (mean 0.42 +/- 0.12 ml/gm/min) had an AVDO2 between 1.3 and 3.0 mumol/ml. A CBF pattern of hyperemia (mean 0.53 +/- 0.18 ml/gm/min) was characterized by an AVDO2 of less than 1.3 mumol/ml. A compensated hypoperfusion CBF pattern (mean 0.23 +/- 0.07 ml/gm/min) was identified by an AVDO2 of more than 3.0 mumol/min. These studies suggest that reliable estimates of CBF may be made from AVDO2 and AVDL measurements, which can be easily obtained in the intensive care unit. PMID- 2913222 TI - New long-wavelength Nd:YAG laser at 1.44 micron: effect on brain. AB - A wavelength-shifted Nd:YAG laser, tuned to coincide with the infrared absorption peak of water at 1.44 microns, was used to make lesions in normal rabbit brain. A total of 48 lesions were made with power up to 20 W, with energy up to 40 joules, and with two different spot sizes. These lesions were compared to lesions made with 1.06 microns radiation from an Nd:YAG laser under identical operating conditions. Measurements of blood-brain barrier damage and width, depth, and volume of tissue affected were obtained 30 minutes after placement of the lesions. It was found that 1.44-microns lesions produced photoevaporative tissue loss at the highest intensities used. The layer of coagulated tissue remaining after photovaporization had a mean thickness of 0.6 mm irrespective of the volume of tissue removed. There was no photovaporization in the 1.06-microns lesions. In addition, the amount of peripheral edema per unit volume of tissue coagulated was approximately half at the 1.44-microns wavelength. These findings suggest that the 1.44-microns Nd:YAG laser may be a useful surgical instrument since it combines the photoevaporative effect of the CO2 laser while maintaining the advantages of the conventional Nd:YAG laser (quartz fiber delivery and effective hemostasis). PMID- 2913223 TI - Effect of dorsal-column stimulation on gelatinosa and marginal neurons of cat spinal cord. AB - Single neuronal units with physiological characteristics of superficial dorsal horn neurons were recorded extracellularly in laminae 1, 2, and 3 of cat spinal cord. When focal electrical stimulation was applied to the ipsilateral dorsal column, most of the units were excited transsynaptically at various latencies consistent with an effect mediated by large myelinated axons. Units recorded in laminae 2 and 3 had earlier latencies of activation than units in lamina 1. Units with cutaneous receptive fields only for noxious stimuli were activated at significantly longer latencies than units responsive to innocuous stimuli. The time course of these effects was consistent with the concept that many cells in laminae 1 to 3 receive direct excitatory synaptic input from collaterals of dorsal-column fibers, and some lamina 1 cells receive excitatory synaptic input from lamina 2 neurons. Previous reports have emphasized the inhibitory action of dorsal-column stimulation on nociceptive responses of cells in laminae 4 and 5 of the dorsal-horn, particularly those of the spinocervical tract in cats and the spinothalamic tract in primates. The present study suggests that some of this inhibition might be sustained by a network of interneurons in or near the substantia gelatinosa and marginal layer. The therapeutic efficiency of dorsal column stimulation for pain relief in humans may depend in part on the activation of neurons in the superficial layers of the dorsal horn. PMID- 2913224 TI - Intrasellar persistent trigeminal artery associated with a pituitary adenoma. Case report. AB - The case of a patient with Cushing's disease and a pituitary macroadenoma, who also had a persistent trigeminal artery coursing through the sella turcica on preoperative imaging studies, is presented. The patient was treated by transsphenoidal resection of the tumor. PMID- 2913225 TI - Intracranial chondroma in a patient with Ollier's disease. Case report. AB - A case is presented in which a solitary chondroma arose from the clivus of a patient with Ollier's disease. These tumors are rare. The diagnostic value of computerized tomography and magnetic resonance imaging is discussed. PMID- 2913226 TI - A new insulated caudalis nucleus DREZ electrode. Technical note. AB - A new insulated radiofrequency electrode for making nucleus caudalis dorsal root entry zone lesions reduces the incidence of ataxia. PMID- 2913227 TI - Vertebral body impactor for posterior lateral decompression of thoracic and lumbar fractures. Technical note. AB - A hand-held impactor is described that allows secure impaction of retropulsed vertebral body bone fragments in burst fractures of the thoracic or lumbar spine. PMID- 2913228 TI - Recurrence of cerebellar astrocytoma. PMID- 2913229 TI - Results of Spinal Task Force survey. PMID- 2913230 TI - The future direction of nutrition research: a nutrition and food sciences agency is the key to progress. PMID- 2913231 TI - The future direction of nutrition research: increasing our scope and the application of new technology to nutritional science. PMID- 2913232 TI - Effect of dietary n-3 fatty acids on weight gain and liver polar lipid fatty acid composition of fingerling channel catfish. AB - A 10-wk experiment was conducted to determine the effect of supplementing a 5% tristearin basal diet with linoleic acid [18:2(n-6)], linolenic acid [18:3(n-3)], an n-3 highly unsaturated fatty acid (n-3 HUFA) mixture, cod liver oil, corn oil or linseed oil on growth and fatty acid composition of the liver polar lipid fraction of fingerling channel catfish (Ictalurus punctatus). The lowest weight gain was observed in fish fed the basal diet. Weight gain was improved by certain levels of supplemental n-3 fatty acids. Fish fed a diet containing 2% 18:3(n-3) grew at the same rate as fish fed a diet containing 2.5% cod liver oil plus 2.5% corn oil. The best growth rate was observed in fish fed diets containing either 5% cod liver oil or 5% linseed oil. Growth rate was depressed by supplementation with 4% 18:3(n-3) or 1.25% n-3 HUFA mix. No improvement in growth rate was observed with dietary 18:2(n-6). Dietary linolenate was converted to docosahexaenoic acid [22:6(n-3)]. The ratio of 20:3(n-9) to 22:6(n-3) of the fish showing good growth was less than 0.4. The data obtained in this experiment indicate that n-3 fatty acids are essential for channel catfish and that the 18:3(n-3) or n-3 HUFA dietary requirement is 1.0-2.0% or 0.5-0.75%, respectively. PMID- 2913233 TI - Effect of vitamin A deficiency on nitrogen balance and hepatic urea cycle enzymes and intermediates in rats. AB - After 12 wk of feeding a 4-d nitrogen balance was carried out in 8 vitamin A- deficient and 8 pair-fed control rats to understand the effect of vitamin A deficiency on protein metabolism. Urea nitrogen (UN) was lower and amino nitrogen (AN) was higher in plasma of deficient animals than in pair-fed controls. No significant alteration in the nitrogen retention or in the general pattern of other nitrogen metabolites in plasma and urine was observed in vitamin A- deficient rats as compared to controls. However, there was a significant increase in the excretion of urinary ammonium nitrogen (Am-N) in relation to creatinine (CR). Activities of hepatic carbamoylphosphate synthase-I (CPS-I) and ornithine transcarbamoylase (OTC) were significantly lower in vitamin A--deficient animals than in control rats at the end of 13 wk of feeding. While the liver levels of ornithine and polyamines were significantly greater, that of glutamine was lower in vitamin A--deficient rats than in pair-fed controls. The results suggest that vitamin A deficiency leads to a reduced efficiency of urea synthesis pathway, thus accounting for the increased Am-N excretion seen in vitamin A deficiency. PMID- 2913234 TI - The fate of dietary pyridoxine-beta-glucoside in the lactating rat. AB - [3H]5'-O-(beta-D-glucopyranosyl) pyridoxine (PN-glucoside) and [14C]pyridoxine (PN) were orally administered to lactating rats. Milk was collected from the dam, and the stomach contents and liver were collected from the suckling pups 24 and 48 h after administration. Analysis of the isotopic ratio (3H/14C) in the milk and stomach contents indicated that the secretion of 3H in the milk was 20-25% as great as the secretion of 14C. The only labeled form of 3H and 14C in the stomach contents was pyridoxal phosphate (PLP), indicating that PN-glucoside was hydrolyzed to PN and subsequently metabolized prior to secretion by the mammary gland. The isotopic ratio in the livers of the pups was similar to that of the stomach contents. Furthermore, the relative distribution of the two isotopes among the hepatic metabolites of the pups was similar. The results of this study indicate that intact PN-glucoside is not secreted in milk, although vitamin B-6 derived from the limited hydrolysis and metabolism of PN-glucoside is delivered to the mammary gland for secretion. PMID- 2913235 TI - Brain histidine and food intake in rats fed diets deficient in single amino acids. AB - Histidine (His) is elevated in plasma and brain during protein deficiency as well as in several pathological conditions, leading to the possibility of a direct effect on central nervous system (CNS) function. In this study, groups of weanling rats were fed diets containing graded levels of casein or a single indispensable amino acid (IAA: Leu, Val, Ile, Phe, Trp, Thr, Met or Lys) in order to produce nutritionally-deficient states. Body weight gains and food intakes were recorded daily for 2 wk. Whole brain and serum samples were obtained and analyzed for amino acid (AA) content. All weight gain and food intake responses could be predicted by the Saturation Kinetics Model. The only consistent pattern observed in AA profiles which could be correlated with food intake was an increase in brain His concentrations. Limiting dietary casein or IAA elevated brain His above controls 2.5- and 1.5-fold, respectively. Food intake was generally depressed by 50% at brain His concentrations above 105 nmol/g. Since His is the precursor of the depressant neurotransmitter histamine (HA), systemic increases may be significant in that HA could be a possible cause of the anorexia observed in protein and IAA deficiency. PMID- 2913236 TI - Effects of aspartame and carbohydrate administration on human and rat plasma large neutral amino acid levels and rat brain amino acid and monoamine levels. AB - Thirty fasted human volunteers were given 0.83 and 8.3 mg aspartame/kg body weight alone, as part of a basal low carbohydrate meal (648 kcal, 10% carbohydrate) or as part of a high energy carbohydrate-rich meal (1290 kcal, 34% carbohydrate). Amino acid concentrations in plasma were determined before and 30, 60 and 180 min after the consumption of aspartame. Under these conditions, which mimic realistic aspartame consumption, aspartame had no significant effect on plasma concentration of any amino acid. In addition, the effect of aspartame alone or with carbohydrates on plasma and brain amino acid levels was studied in rats after acute or subacute (14 d) oral treatment. In subacute dosing experiments aspartame was included in the diet. Brain monoamine concentrations were also measured in the same animals. Plasma concentrations of large neutral amino acids were modified under acute conditions. In contrast, after subacute treatment no significant differences in plasma or brain amino acid concentrations or in brain monoamine concentrations were observed. PMID- 2913237 TI - The role of liquid diet formulation in the postnatal ethanol exposure of rats via mother's milk. AB - The nutritional adequacy of three liquid diets containing ethanol to support lactation was studied in rats. Diets 1 and 2 provided 18 and 25% kcal, respectively, as protein with 36% of total calories as ethanol, while in diet 3 alcohol provided 28% and protein 25% of total calories. Three series of isoenergetically pair-fed rats, as well as an ad libitum group fed a solid diet, were studied. A primary maternal malnutrition was evident in rats fed diet 1. With respect to diet 2, the 96% postnatal mortality which occurred may have been due to an inhibition of milk production mediated by exaggerated blood alcohol concentrations present in the lactating dams. Diet 3 seemed to be nutritionally adequate for the extra requirements for lactation and a direct effect of ethanol was observed in the sucklings. High blood alcohol levels (25-50 mmol/1) were obtained in dams fed ethanol diets 1 and 3; however only 1% of maternal blood alcohol appeared in the blood of sucklings, demonstrating a low transfer of ethanol from mother to offspring through the milk. Finally the model for postnatal exposure to alcohol via mother's milk is discussed in terms of other indirect alcohol-related factors which make it difficult to evaluate the direct impact of ethanol per se in the normal development of the suckling pups. PMID- 2913238 TI - The effect of pectin on hepatic lipogenesis in the enterally-fed rat. AB - The fermentation of pectin by colonic bacteria produces short-chain fatty acids (SCFA) which are then absorbed by the host. The purpose of this study was to determine whether pectin, added to a chemically defined diet, would increase hepatic lipogenesis and whether this effect is mediated by intestinal bacteria. Eighteen Sprague-Dawley rats underwent placement of a feeding gastrostomy and a swivel apparatus. Postoperatively, rats were randomly assigned to one of three groups: 1) No Pectin received a fat-free chemically defined diet, 2) Pectin received the same diet with the addition of 1% (w/v) pectin, and 3) Neomycin received the same diet with 1% w/v pectin and neomycin (80 mg/kg of body weight daily). On the 5th postoperative d, all diets included 12.5% (v/v) deuterium as D2O. After the infusion of the labeled diets for 24 hr, the content and deuterium enrichment of liver palmitate, stearate and oleate were measured and the production rates calculated. The liver content and production rates of these fatty acids were higher in Pectin animals than in either the No Pectin or Neomycin animals. Since the effect of pectin on hepatic lipogenesis was reduced by the concomitant administration of the intestinal antibiotic neomycin, it appears that this effect depends on the bacterial fermentation of pectin. It is postulated that the SCFA produced during pectin fermentation promote lipogenesis via a direct stimulatory effect, in addition to being carbon donors. PMID- 2913239 TI - Biological actions of carotenoids. Symposium proceedings. Las Vegas, NV, May 2, 1988. PMID- 2913241 TI - Are safety and personal freedom miles apart? PMID- 2913240 TI - Biological actions of carotenoids. AB - Of approximately 600 naturally occurring characterized carotenoids, fewer than 10% serve as precursors of vitamin A in mammals. Apart from vitamin A formation, carotenoids show unique physicochemical properties and interesting biological effects. The inverse association between the ingestion of carotenoid-containing fruits and vegetables and the risk of certain forms of cancer has attracted significant attention. In considering the effects of carotenoids in mammals, a distinction should clearly be made among functions, actions and associations. Furthermore, carotenoids might well be classified in relation to defined biological actions, and not just in relation to nutritional activity. PMID- 2913242 TI - Different speeds for different needs. PMID- 2913243 TI - Saving lives by not drinking and driving. PMID- 2913244 TI - Open reduction of the dislocated, fractured condylar process: indications and surgical procedures. AB - The subject of this paper is the evaluation of the results after surgical management of 29 dislocated fractures of the condylar process. Only fractures with total dislocation of the condyle out of the articulate fossa were surgically treated. The surgical procedure, making a broad exposure necessary, is detailed. The low rate of complications as well as the satisfactory function of the joints in spite of severe dislocation seems to confirm the surgical treatment of this type of fractures. PMID- 2913245 TI - Stability following combined maxillary and mandibular osteotomies treated with rigid internal fixation. AB - Skeletal stability was examined in 16 patients following combined maxillary and mandibular osteotomies using rigid internal fixation. Postoperative changes (T2 to T3) were generally less than 1.0 mm for linear measurements and less than 2.0 degrees for angular measurements. The removal of maxillomandibular fixation (MMF) splints accounted for 85% to 95% of the counterclockwise rotation in the proximal and distal mandibular segments from T2 to T3. Maxillary inferior repositioning and large mandibular advancements exhibited the greatest tendency for relapse; however, the changes were less than with comparable procedures using nonrigid methods for stabilization. Except for large mandibular advancements, relapse was essentially unrelated to the magnitude of the surgical repositioning. Although the use of skeletal, maxillomandibular, and transosseous wire fixation have traditionally provided satisfactory clinical results, the use of rigid internal fixation in combined osteotomy procedures provides better stabilization of dentosseous segments when compared with these nonrigid methods, and may be particularly indicated in complex surgical procedures. PMID- 2913246 TI - Use of collagen tubes containing particulate hydroxylapatite for augmentation of the edentulous atrophic maxilla: a preliminary report. AB - Collagen tubes of specific configuration containing particulate hydroxylapatite were placed by a palatal approach to augment edentulous atrophic maxillas. Both the ability to chew and comfort of the denture were improved in the 12 reported cases. Eleven cases showed solidification of the implant between 8 and 16 weeks. There was no problem with particle migration or loss of vestibular height. PMID- 2913247 TI - The use of a pedicled temporalis muscle-pericranial flap for replacement of the TMJ disc: preliminary report. AB - Disc replacement in temporomandibular joint surgery has been troublesome. Problems such as migration, fragmentation, foreign body reactions, and unpredictable biodegradation have occurred. Autogenous tissue is presently the material of choice, but requires a second surgical site. In addition, it is a free graft, and thus its fate is unknown. A technique has been developed that uses a pedicled autogenous flap composed of a portion of the temporalis muscle and pericranium to act as an interpositional material in temporomandibular joint surgery. The flap, based on the deep temporal arteries, and pedicled off of the coronoid process, is rotated anterior to the articular eminence and then posteriorly into the temporomandibular joint where it is sutured to the retrodiscal tissue. This procedure allows maintenance of tissue viability and functional movement of the flap during mandibular excursions. The technique offers numerous advantages over the existing autogenous, allogeneic, and alloplastic materials presently used in temporomandibular joint surgery. PMID- 2913248 TI - Incidence of oxygen desaturation during oral surgery outpatient procedures. AB - The frequency, severity, and duration of oxygen desaturation during oral surgical procedures in outpatients was measured. Sixty patients divided into six groups received either lidocaine; lidocaine, diazepam, and meperidine; lidocaine, diazepam, meperidine, and headphone music; lidocaine, diazepam, meperidine, and nitrous oxide; lidocaine, diazepam, meperidine, methohexital, and nitrous oxide; or lidocaine and nitrous oxide. Forty-three percent of the 30 patients who did not receive supplemental oxygen experienced clinically significant oxygen desaturation (greater than 5%) with a mean duration of 4.6 minutes. Only 13% of the patients who received supplemental oxygen had significant desaturation ranging from ten seconds to 12.3 minutes with a mean duration of 1.4 minutes. An unexpected finding was hypoxia in patients receiving only lidocaine anesthesia. PMID- 2913249 TI - Eminectomy and discoplasty for correction of the displaced temporomandibular joint disc. AB - Eminectomy with or without a subsequent discoplasty was performed on 30 patients (36 joints) with internal derangement of the temporomandibular joint (TMJ) confirmed either arthrographically or with magnetic resonance imaging. The importance of the inclination of the TMJ eminence and the therapeutic value of eminectomy are discussed. The TMJs were clinically evaluated before and at least 1 year after surgery in respect to opening function and symptoms. The results were promising (86.8% of the patients felt better). In five patients with a preoperative diagnosis of anterior disc displacement with reduction, only an eminectomy was performed. In these five cases eminectomy alone was sufficient to restore normal TMJ function. PMID- 2913250 TI - Duration of amnesia associated with midazolam/fentanyl intravenous sedation. AB - The purpose of this study was to determine the duration of amnesia associated with the intravenous usage of midazolam and fentanyl. The midazolam was administered in three different dosages based on the patient's weight in kilograms. Patients were shown a series of pen-and-ink drawings at various times throughout the procedure and tested the next day for memory of the drawings using both free recall and match-to-sample paradigms. The results indicate that the low dosage group (0.07 mg/kg) had insufficient amnesia, whereas the medium (0.10 mg/kg) and high (0.13 mg/kg) groups displayed adequate amnesia in the intraoperative period. PMID- 2913251 TI - Inferior mandibular osteotomy and hyoid myotomy suspension for obstructive sleep apnea: a review of 55 patients. AB - Fifty-five patients with obstructive sleep apnea syndrome (OSAS) were evaluated following inferior mandibular osteotomy with hyoid myotomy and suspension. Patients were objectively examined by polysomnography before and 6 months following the surgical procedure. Thirty-seven patients (67%) had a good response from surgery, and 18 patients (33%) were considered nonresponders. Lung disease, mandibular deficiency, and obesity were factors found to affect the success of surgical treatment. PMID- 2913252 TI - A double-blind study on the effectiveness of tetracycline in reducing the incidence of fibrinolytic alveolitis. AB - This study presents the results of a double-blind study evaluating the effectiveness of topical tetracycline used as a suspension in a square of gelatin sponge and placed in the sockets of extracted mandibular third molars for the prevention of dry socket. An assessment of the relationship between the amount of bone relief (trauma) incidental to the surgery and the occurrence of dry socket also is made. Dry socket occurred in 20.4% of the placebo-treated sockets, whereas the incidence in the tetracycline-treated sockets was 3.9%. No correlation was observed between the amount of bone relief attendant to the surgery and the incidence of dry socket. It is concluded that tetracycline is an effective prophylaxis for fibrinolytic alveolitis. PMID- 2913253 TI - Granular cell odontogenic cyst: a unicystic ameloblastoma with late recurrence as follicular ameloblastoma. AB - This report is a follow-up of the original case of granular cell odontogenic cyst described by Gold and Christ in 1970. The lesion, originally treated by enucleation in 1965, recurred 18 years later as a follicular ameloblastoma with prominent plexiform and acanthomatous histologic patterns. No histologic evidence of granular cells was noted in the recurrent lesion. The recurrent ameloblastoma was treated by marginal resection of the body of the mandible and immediate reconstruction with an iliac bone graft. The anatomic restoration was excellent, and there is no recurrence 5 years postoperatively. This case supports the view that the granular cell odontogenic cyst is a unicystic (monocystic) granular cell ameloblastoma, and that the presence of granular cells in ameloblastoma is not a permanent feature and may be of little value as a prognostic indicator of aggressiveness. PMID- 2913254 TI - Surgical management of a large, complex mandibular odontoma by unilateral sagittal split osteotomy. PMID- 2913255 TI - Hemiplegic migraine following third molar extractions under intravenous sedation: report of a case. PMID- 2913256 TI - Modified rhytidectomy approach for total temporomandibular joint reconstruction: a case report. AB - A case is reported in which a modified rhytidectomy incision is used to access both the TMJ and the lateral ramus for total TMJ reconstruction. This approach hides the incision in the neck hairline and eliminates the retromandibular incision scar. PMID- 2913257 TI - Transmaxillary temporalis transfer for reconstruction of a large palatal defect: report of a case. AB - The infratemporal transmaxillary transfer of a temporalis myofascial flap for reconstruction of an extensive palatal defect in an adult cleft palate patient is described. A modified temporal approach is discussed. PMID- 2913258 TI - Modified reduction genioplasty. PMID- 2913259 TI - A method for repositioning a mandibular fracture with delayed union and/or nonunion. PMID- 2913260 TI - A technique of fixation of costochondral grafts for reconstruction of the temporomandibular joint. PMID- 2913261 TI - Multidisciplinary issues in intravenous therapy: therapeutic and clinical trends. PMID- 2913262 TI - Vascular access devices. Hospital to home care. PMID- 2913263 TI - What is the real price of cost containment? PMID- 2913264 TI - Iv specialization: current issues. PMID- 2913265 TI - Spontaneous regeneration of free muscarinic receptor after alkylation by BM 123. I. Recovery in vivo and in cell culture. AB - The recovery of rat muscarinic receptor number from the effects of a specific alkylating ligand, N-[4-(2-chloroethylmethylamino)-2-butynyl]-2-pyrrolidone (BM 123), in three tissues is presented as an exponential function of time. No significant difference was found in the recovery rate constants derived from analysis of recovery time courses in corpus striatum, cerebral cortex and ileal longitudinal muscle. The single rate constant (0.021/hr) was also independent of amount and duration of BM 123 dose. Additional analysis of agonist-defined high and low affinity subsites in cortex revealed that recovery of these populations also followed similar time courses although the alkylation proceeds more slowly for the high affinity sites. The rate constant for recovery of both subsites was 0.029/hr. Recovery from BM 123 alkylation occurred in NG108-15 neuroblastoma X glioma cells. The presence of cycloheximide in the recovery medium did not significantly inhibit this recovery process in the clonal cell line, suggesting that de novo receptor synthesis is unnecessary for regeneration of unalkylated receptors. PMID- 2913266 TI - Spontaneous regeneration of free muscarinic receptor after alkylation by BM 123. II. Recovery in broken cell preparations. AB - Muscarinic receptors from rat cerebral cortex were found to recover from alkylation by the specific ligand N-[-(2-chloroethyl-methylamino)-2-butynyl]-2 pyrrolidone (BM 123) without the benefit of cellular integrity, i.e., in washed membranes incubated at 37 degrees C for relatively long times (days). Unalkylated receptor number increased in alkylated preparations whether viewed as femtomoles per milligram of protein or as a percentage of the atropine-protected control. The rate of recovery was independent of pH over the range 6 to 9 and it was slowed but not eliminated by incubation at 4 degrees C. Muscarinic receptor recovery from BM 123 was linearly dependent on the concentration of alkylated receptors, indicating first-order kinetics and yielding a rate constant 0.026/hr. Of the other chloroethylamines examined for evidence of in vitro muscarinic receptor recovery from alkylation, only one, phenoxybenzamine, exhibited irreversible receptor blockade under these conditions. Each of the others showed different rates for regeneration of free receptors. PMID- 2913267 TI - Acute opioid physical dependence in postaddict humans: naloxone dose effects after brief morphine exposure. AB - Antagonist-precipitated withdrawal after acute opioid administration (acute physical dependence) is an interesting phenomenon in that the opioid abstinence syndrome is generally thought to develop only after prolonged exposure to opioid agonists. The purpose of this study was to examine further this phenomenon in humans by characterizing the antagonist dose-response function. The effects of i.m. naloxone (0, 0.1, 0.3, 1, 3, 10 and 30 mg/70 kg) were assessed 6 hr after single i.m. injections of morphine (18 or 30 mg/70 kg) in six subjects with a history of chronic opiate use. Naloxone reversed residual morphine effects, including miosis and respiratory depression. The degree of reversal was dose related to 10 mg/70 kg of naloxone with no further increases at the highest naloxone dose. Simultaneously, observer ratings of withdrawal signs and subjective reports of withdrawal symptoms were increased in an orderly dose related manner to 30 mg/70 kg of naloxone. Reversal of residual morphine effects and onset of precipitated withdrawal were evident by 5-min postnaloxone; peak effects occurred within 15 min. This study confirmed the occurrence of antagonist precipitated withdrawal after brief opioid exposure in humans, demonstrated the rapid onset of withdrawal effects and characterized the naloxone dose-response function. PMID- 2913268 TI - Protection by L-2-oxothiazolidine-4-carboxylate, a cysteine prodrug, against 1,1 dichloroethylene hepatotoxicity in rats is associated with decreases in toxin metabolism and cytochrome P-450. AB - Our objective was to determine if the intracellular cysteine precursor, L-2 oxothiazolidine-4-carboxylate (OTZ), would protect rats against the hepatotoxicity of 1,1-dichloroethylene (DCE) by altering the toxin's biologic fate. Fasted male rats were pretreated with 10 mmol of OTZ per kg s.c. in saline or with saline only 1 hr before administration of 14C-labeled DCE (50 mg/kg) p.o. in mineral oil. Serial blood samples were taken from permanent jugular cannulas between 1 and 24 hr to monitor the time course of injury and circulating levels of 14C-derived label. DCE caused less liver injury in the OTZ-pretreated group. This protection was associated with about 50% less total, acid soluble and acid precipitable 14C-label in serum; 30% less label in urine; and at 24 hr, 30 to 68% less covalently bound label in liver, kidney and lung. Extent of peak liver injury in individual animals correlated well with the amount of 14C-label in serum at early times and with the amount covalently bound to liver at 24 hr, but correlated poorly with label excreted into urine. An explanation for the apparent decrease in DCE metabolism by OTZ-pretreated animals was investigated by examining effects of OTZ on liver constituents known to have a role in DCE metabolism. Fasted rats given 10 mmol of OTZ per kg showed a persistent loss of hepatic cytochrome P-450 at 3 and 6 hr whereas their hepatic and renal reduced glutathione contents were transiently diminished at 3 hr.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2913269 TI - Obesity as a risk factor in drug-induced organ injury. IV. Increased gentamicin nephrotoxicity in the obese overfed rat. AB - Obese humans suffer from excessive organ dysfunction, altered drug pharmacokinetics and may be at increased risk of various drug toxicities. A recent report shows that gentamicin nephrotoxicity in critically ill patients is more frequent and more severe than usual in individuals who are substantially overweight. The present study utilizes an overfed rat model to examine the influence of obesity on the nephrotoxic potential of gentamicin. After 52 weeks on an energy-dense diet, obese animals outweighed pellet controls by more than 80% (913 +/- 86 vs. 507 +/- 52 g; X +/- S.D., n = 7). When animals were treated twice daily for 6 days with 30 mg/kg of gentamicin i.p. based on total body mass, obese rats sustained more cortical necrosis than control (median score 3+ vs. 0), higher serum creatinine (4.36 +/- 2.72 vs. 0.71 +/- 0.17) and greater creatinine adjusted N-acetyl hexosaminidase excretion. The impact of obesity on intrinsic susceptibility to gentamicin nephrotoxicity was assessed by dosing animals for 5 days to ideal body mass plus 40% of excess body mass, the current clinical practice for achieving normal gentamicin concentrations in obese patients. Obese rats again sustained more frequent and severe cortical necrosis (2+ vs. 0) and excreted more N-acetyl hexosaminidase than control animals. Urine pH averaged 1.7 U below normal in obese animals, but restoration to normal values by 2 weeks on the pellet diet did not diminish the toxicity increase. Results from the overfed rat closely resemble the recent clinical observation that obese patients sustain more frequent and severe kidney damage from aminoglycoside antibiotics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2913270 TI - Contribution of metabolites to the route- and time-dependent hepatic effects of di-(2-ethylhexyl)phthalate in the rat. AB - The effects of exposure to the plasticizer di-(2-ethyl-hexyl)phthalate (DEHP) and its two primary products of presystemic de-esterification, mono-(2 ethylhexyl)phthalate and 2-ethyl-hexanol, on hepatic microsomal oxidation were investigated in rats. The metabolic clearance of antipyrine was utilized as an in vivo measure of the activity of the hepatic microsomal oxidative enzyme system. Subchronic (7 days) p.o. treatment of rats with DEHP, mono-(2 ethylhexyl)phthalate or 2-ethylhexanol produced a substantial increase in both wet liver weight and antipyrine clearance relative to corn oil-treated controls. In contrast, i.p. administration of DEHP resulted in a minor but statistically significant stimulation of liver growth and antipyrine metabolism. Whereas chronic administration of the plasticizer or its metabolites produced apparent induction of hepatic microsomal oxidative enzymes, administration of a single dose of each compound was associated with immediate inhibition of the metabolism of antipyrine. The present data suggest that the products of deesterification of DEHP are primarily responsible for the stimulation of hepatic metabolism observed after long-term exposure to the plasticizer, whereas the parent compound and both metabolites have the potential to produce acute inhibition of hepatic microsomal oxidation in vivo. PMID- 2913271 TI - Immunochemical quantitation of 3-(cystein-S-yl)acetaminophen adducts in serum and liver proteins of acetaminophen-treated mice. AB - Using a recently developed enzyme-linked immunosorbent assay specific for 3 (cystein-S-yl)acetaminophen adducts we have quantitated the formation of these specific adducts in liver and serum protein of B6C3F1 male mice dosed with acetaminophen. Administration of acetaminophen at doses of 50, 100, 200, 300, 400 and 500 mg/kg to mice resulted in evidence of hepatotoxicity (increase in serum levels of alanine aminotransferase and aspartate aminotransferase) at 4 hr in the 300, 400 and 500 mg/kg treatment groups only. The formation of 3-(cystein-S yl)acetaminophen adducts in liver protein was not observed in the groups receiving 50, 100 and 200 mg/kg doses, but was observed in the groups receiving doses above 300 mg/kg of acetaminophen. Greater levels of adduct formation were observed at the higher doses. 3-(Cystein-S-yl)acetaminophen protein adducts were also observed in serum of mice receiving hepatotoxic doses of acetaminophen. After a 400 mg/kg dose of acetaminophen, 3-(cystein-S-yl)acetaminophen adducts in the liver protein reached peak levels 2 hr after dosing. By 12 hr the levels decreased to approximately 10% of the peak level. In contrast, 3-(cystein-S yl)acetaminophen adducts in serum protein were delayed, reaching a sustained peak 6 to 12 hr after dosing. The dose-response correlation between the appearance of serum aminotransferases and 3-(cystein-S-yl)acetaminophen adducts in serum protein and the temporal correlation between the decrease in 3-(cystein-S yl)acetaminophen adducts in liver protein and the appearance of adducts in serum protein are consistent with a hepatic origin of the adducts detected in serum protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2913272 TI - Gradient in the effects of ethyl alcohol on canine gastric antral circular muscles. AB - The effects of ethyl alcohol on the electrical and mechanical activities of canine gastric antral circular muscle were studied. Recently it has been reported that the circular layer of the antrum is not homogenous in its electrical activity. Therefore, circular muscles from the regions adjacent to the myenteric and submucosal borders of the circular layer were studied separately to compare the actions of ethyl alcohol through the thickness of the circular layer. In the first series of experiments concentration-response data were collected to describe the effects of ethyl alcohol on the contractile activities of myenteric and submucosal muscles. The data show that ethyl alcohol is more effective as an inhibitor of myenteric contractions than submucosal contractions. Next, experiments were performed to determine the electrical mechanism responsible for the contractile effects. Circular cells of submucosal and myenteric regions were impaled, and the muscles were exposed to several concentrations of ethyl alcohol ranging from 0.1 to 1.5%. Slow wave activity was reduced in frequency and amplitude in both regions. The inhibitory effect of ethyl alcohol on electrical activity was greater in submucosal muscles, but mechanical activity was less affected in these muscles because excitation-contraction coupling occurs at more polarized levels in the submucosal portion of the circular layer. PMID- 2913273 TI - Manganese-mediated increase in the rat brain mitochondrial cytochrome P-450 and drug metabolism activity: susceptibility of the striatum. AB - The present study describes the high degree of sensitivity of the mitochondrial fraction of the striatum to Mn++-mediated perturbations in mixed-function oxidase activity. This study also defines the brain mitochondrial cytochrome P-450 subject to increase by Mn++. In the striatum of Mn++-treated animals (7 days) hydroxylation of benzo(a)pyrene and D-amphetamine was significantly increased in both the mitochondrial and the microsomal fractions. The effects were more pronounced in the mitochondrial fraction where hydroxylation activities were increased by 2- to 3-fold. SKF-525A (2-diethylaminoethyl-2,2-di-phenylvalerate hydrochloride) effectively inhibited NADH-dependent hydroxylation of both substrates by the mitochondrial fraction. In the Mn++-treated animals, significant increases in mitochondrial and microsomal cytochrome P-450 concentration were also noted. In the mitochondria, the hemoprotein concentration was increased by nearly 2.5-fold; in the microsomes the concentration of the cytochrome was increased by about 1.6-fold. Mn++ appeared to selectively increase cytochrome P-450 concentration since that of other cytochromes including the mitochondrial b, c1, c and a, and the microsomal cytochrome b5 was not increased. In addition, the activity of mitochondrial delta-aminolevulinate synthetase was not increased and that of the microsomal heme oxygenase was inhibited by Mn++ treatment. It is suggested that increases in the microsomal and the mitochondrial cytochrome P-450 may reflect intrinsic properties of cytochrome P-450 isozymes in these organelles, including their turnover rate, preferential utilization of heme and/or susceptibility to degradation. The possible relevance of the findings to Mn++ neurotoxicity of dopamine pathways is discussed. PMID- 2913274 TI - Bradykinin stimulates electrogenic bicarbonate secretion by the guinea pig gallbladder. AB - We studied bradykinin effects upon electrogenic ion transport across voltage clamped guinea pig gallbladder, and found stimulation after both mucosal (EC50 = 0.2 microM) and serosal addition (EC50 = 10 microM). The mucosal effect is dose dependent, reproducible and sustained. Responses to bradykinin were unaffected by amiloride (1 mM) or piretanide (1 mM) but were attenuated by acetazolamide (1 mM), indicating the charge-carrying ion species to be bicarbonate. This was confirmed by abolishing the short circuit current response to bradykinin with bicarbonate-free solutions. Tetrodotoxin (1 microM) did not alter the response, indicating that neurons are not involved. This effect of bradykinin on gallbladder bicarbonate transport appears to be dependent upon arachidonate metabolism because the cyclooxygenase inhibitor piroxicam reversibly abolished the effect. In addition, prostaglandin E2 was more effective (EC50 = 0.01 microM) than bradykinin in stimulating short circuit current. This newly appreciated ion transporting effect of bradykinin occurs in a tissue where kinin effects upon afferent nerve endings and smooth muscle are also evident and raise several questions about kinin involvement in stone formation or local inflammatory events. PMID- 2913275 TI - Effects of ketoprofen and indomethacin on leukocyte migration in two models of pleurisy induced by carrageenan or zymosan-activated serum in rats. AB - The effect of nonsteroidal anti-inflammatory drugs on the in vivo leukocyte migration is not understood fully. In the present study, the effects of indomethacin and ketoprofen on the intrapleural leukocyte accumulation induced by carrageenan or zymosan-activated serum (ZAS) were investigated. Rats were given indomethacin or ketoprofen p.o. (1, 3 or 9 mg/kg) 1 hr before intrapleural injection of carrageenan (1 mg) or ZAS (0.5 ml). Pleural exudates were harvested 4 hr later. In each model of pleurisies, ketoprofen and indomethacin reduced the volume of exudate and leukocyte count in a dose-dependent manner but ketoprofen was more active than indomethacin. Ketoprofen and indomethacin had no effect on the protein concentration and the total complement activity of the exudates induced by carrageenan or ZAS. The spontaneous and directed migrations of leukocytes elicited by ZAS were unaffected by indomethacin and ketoprofen, whereas those of leukocytes elicited by carrageenan were more inhibited by ketoprofen than by indomethacin. These data demonstrate that ketoprofen is more active than indomethacin in reducing the in vivo leukocyte migration evoked by carrageenan or ZAS and suggest that the main effect of these two drugs is to reduce the increase in vascular permeability. Neutrophil chemotactic responsiveness and generation of chemotactic factors alone cannot explain the anti-inflammatory effect of ketoprofen and indomethacin. PMID- 2913276 TI - Beneficial effects of lidocaine and disopyramide on oxygen-deficiency-induced contractile failure and metabolic disturbance in isolated rabbit hearts. AB - The purpose of the present study was to determine whether antiarrhythmic agents, lidocaine and disopyramide, which reveal a membrane stabilizing action, may exert a beneficial effect on posthypoxic recovery of cardiac function and metabolism. Rabbit hearts were perfused for 20 min under hypoxic conditions, followed by 45 min reoxygenation. Hypoxic insults induced cessation of cardiac contractile force, rise in resting tension, depletion of myocardial high-energy phosphates, accumulation of tissue calcium and release of creatine kinase and ATP metabolites such as adenosine, inosine and hypoxanthine. These alterations were not returned to the initial levels upon reoxygenation. Administration of either 69 microM lidocaine or 55 microM disopyramide after the onset of oxygen deficiency (between 8th and 20th min of the hypoxia) resulted in a significant suppression of hypoxia induced rise in resting tension, tissue calcium accumulation and release of creatine kinase and ATP metabolites, whereas hypoxia-induced decline in cardiac contractile force and depletion of myocardial high-energy phosphates were not affected by the treatment. The latter two variables were improved markedly during 45-min reoxygenation when the heart had been treated with the agents. The improvement was accompanied by a suppression of the release of creatine kinase and ATP metabolites and the tissue calcium accumulation. The results suggest that lidocaine and disopyramide are beneficial for posthypoxic recovery of cardiac function and metabolism. PMID- 2913277 TI - Paraxanthine metabolism in humans: determination of metabolic partial clearances and effects of allopurinol and cimetidine. AB - Paraxanthine (PX; 1,7-dimethylxanthine) is the major metabolite of caffeine in humans. Despite the continuous exposure of a large proportion of the population to PX, little is known about PX disposition in humans. The present study was performed to define the metabolic partial clearances of PX in humans and, by determining the effects of cimetidine and allopurinol pretreatments on PX disposition, assess the relative importance of cytochrome P-450 and xanthine oxidase in PX biotransformation. The combined formation of the 7-demethylated products 1-methylxanthine (1-MX), 1-methyluric acid (1-MU) and 5-acetyl-amino-6 formylamino-3-methyluracil (AFMU) accounted for 67% of PX clearance. Formation of 7-methylxanthine (7-MX) and 1,7-dimethyluric acid and renal excretion of unchanged PX comprised 6, 8 and 9% of PX clearance, respectively. Allopurinol pretreatment had no effect on PX plasma clearance but decreased 1-MU excretion and increased 1-MX excretion, with the combined excretion of these metabolites remaining constant. Cimetidine pretreatment decreased PX plasma clearance by 30%. Metabolic partial clearances to 1-MX + 1-MU and to AFMU were reduced to a similar extent (ca. 40%) in the cimetidine treatment phase, but other pathways were not significantly affected. These data are consistent with 1-MX and AFMU being derived from a common intermediate, the formation of which is mediated by cytochrome P-450. Xanthine oxidase catalyzes only the secondary conversion of 1 MX to 1-MU. PMID- 2913278 TI - Plasma arginine vasopressin response to intravenous methadone and naloxone in conscious dogs. AB - The effect of naloxone and methadone on the systemic release of arginine vasopressin (AVP) was studied in six conscious dogs. After i.v. methadone administration (1 mg/kg b.wt.) plasma AVP levels rose significantly to a mean maximum value of 102.8 +/- 18.8 pg/ml at 15 min postinjection. Plasma sodium and plasma osmolality did not change significantly, whereas plasma potassium decreased significantly. Blood gas variables showed the development of a slight respiratory acidosis. Mean arterial blood pressure increased and heart rate decreased, both significantly, after methadone administration. Naloxone (0.1 mg/kg b.wt.) administered i.v., 15 min before methadone, prevented the changes in plasma AVP levels as well as other variables, with the exception of the heart rate. Naloxone administration itself did not induce changes in any variable recorded. The dose-response study showed increasing plasma AVP levels upon administration of increasing doses of methadone above the 0.5 mg/kg level. On account of the magnitude of response and the lack of changes in biochemical and hemodynamic variables sufficient to explain the documented AVP response, we conclude that methadone exerts a stimulatory influence on the systemic release of AVP. We consider the documented release of AVP to be a direct effect of the methadone administration, on account of the findings from the dose-response study and on account of the total blockade of the response after naloxone administration before methadone. PMID- 2913279 TI - Interaction of the prejunctional inhibitory action of 5-hydroxytryptamine on noradrenergic transmission with neuronal amine uptake in rabbit isolated ear artery. AB - The interaction of the prejunctional inhibitory action of 5-hydroxytryptamine (5 HT) on noradrenergic transmission with the neuronal amine uptake mechanism has been studied in rabbit isolated ear artery preparations. Release of norepinephrine in response to stimulation of periarterial sympathetic nerves (30 pulses, 1 Hz) was deduced from the efflux of radioactivity which had been incorporated into the noradrenergic transmitter pool as [3H]norepinephrine. 5-HT (100 nM), applied alone, had no effect on the stimulation-induced efflux of radioactivity. However, in the presence of cocaine (1 microM), 5-HT reduced stimulation-induced efflux. The inhibitory effect of 5-HT, in the presence of cocaine, on stimulation-induced efflux was abolished by the nonselective 5-HT1/5 HT2 receptor antagonist, methiothepin (30 nM), but not by the selective 5-HT2 receptor antagonist, ketanserin (6 nM), or by the alpha adrenoceptor antagonist, phentolamine (30 nM). These findings indicate that the uptake of 5-HT into periarterial sympathetic nerves may limit its prejunctional "5-HT1-like" receptor mediated inhibitory effect on noradrenergic transmission. In arteries which were incubated with 5-HT (1 microM) and the monoamine oxidase inhibitor, pargyline (10 microM), before loading the transmitter stores with [3H]norepinephrine, methiothepin (30 nM) enhanced stimulation-induced efflux markedly. The enhancing effect of methiothepin was not observed in arteries which were preincubated with cocaine (10 microM) together with 5-HT and pargyline. It is suggested that, following its uptake into periarterial sympathetic nerves, 5-HT may be coreleased with norepinephrine to activate prejunctional 5-HT1-like receptors and thereby mediate an autoinhibitory effect on transmitter release. PMID- 2913280 TI - In vivo mechanisms for the enhanced acetylation of sulfamethazine in the rabbit after hydrocortisone treatment. AB - The administration of hydrocortisone (HC; 75 mg/kg i.v. daily for 10 days) to rabbits significantly increased the metabolic clearance (Clm) of sulfamethazine (SMZ) from 1.92 +/- 0.05 to 2.85 +/- 0.06 liters/hr/kg (P less than 0.01). However, p.o. availability of SMZ was similar before (0.42 +/- 0.06) and after (0.39 +/- 0.03) steroid treatment. Furthermore, total liver blood flow as measured by the radioactive microsphere technique was increased (P less than 0.01) from 3.64 +/- 0.15 to 5.12 +/- 0.54 liters/hr/kg by HC treatment. Estimates of presystemic intestinal extraction and hepatic extraction were derived. These data predicted that intestinal extraction ranged from 0.11 to 0.15 in untreated rabbits and from 0.11 to 0.16 in HC-treated rabbits. Moreover, intestinal clearance was shown to contribute less than 4% to Clm of SMZ on both study days. By comparison, estimates of hepatic extraction ranged from 0.51 to 0.53, and from 0.54 to 0.56 in untreated and HC-treated rabbits, respectively. Based on the concept of a well-stirred, perfusion-limited model of hepatic elimination, the HC induced increases in hepatic enzyme activity and blood flow were shown to make comparable contributions to the increase in hepatic clearance. It is concluded that the liver is the major site of SMZ acetylation in untreated and HC-treated, rapid acetylator rabbits. Furthermore, the increase in Clm of SMZ observed in vivo after HC treatment is attributable primarily to increases in hepatic N acetyltransferase activity and liver blood flow. PMID- 2913281 TI - Altered responsiveness to sympathetic nerve stimulation and agonists of isolated left atria of diabetic rats: no evidence for involvement of hypothyroidism. AB - To clarify the role of hypothyroidism in diabetes-induced sympathetic neuropathy, we examined the responsiveness to sympathetic nerve stimulation and to agonists of the left atria of streptozotocin-induced diabetic rats, and compared it with those in hypothyroid, thyroxine(T4)-treated diabetic or T4-treated hypothyroid rats. Positive inotropic response of isolated left atria to transmural nerve stimulation (TNS) was examined in the presence of atropine. In diabetic rats, plasma triiodothyronine and T4 levels decreased markedly. The responses to TNS and norepinephrine (NE) also decreased. The decrease was greater in response to TNS, which may be due to the reduction of presynaptic NE release. As to the postsynaptic response, the maximal response to NE decreased without any significant change in ED50 value, and a similar decrease in the maximal response to Ca++ was also observed in spite of a slight decrease in the beta receptor density. Therefore, in diabetic rats the decreased response to TNS may result mainly from a decreased NE release from nerve endings and a decreased contractility beyond the adrenoceptor level. In hypothyroid rats, the response to TNS and NE decreased, and the decrease was again greater in response to TNS. The decrease in the NE response was due to the increased ED50 value without any change in the maximal response. Similarly, the maximal response to Ca++ did not change. Thus in the hypothyroid rats, the decreased response to TNS probably results from a decreased NE release from nerve endings as well as a decreased sensitivity to NE.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2913282 TI - Effects of coronary flow, pacing rate, isoprenaline and diltiazem on ischemic ventricular arrhythmias in guinea pig hearts. AB - Although the Ca++ channel blockers can reduce early ischemic ventricular arrhythmias, the mechanisms are unclarified. The antiarrhythmic action of Ca++ antagonists may either be due to vasodilation and negative chronotropism or to trans-sarcolemmal Ca++ influx inhibition. In these studies we investigated the possible individual and additive effects of coronary flow, heart rate and Ca++ antagonism on ventricular arrythmia development in isolated, paced, globally underperfused guinea pig hearts. When the coronary flow during ischemia was raised from 5 to 7% of control and/or the stimulation frequency was decreased from 6 to 4 Hz, ATP and creatine phosphate levels were conserved and intraventricular conduction slowing leading to ventricular tachycardia (VT) was delayed. In contrast, when the coronary flow and pacing rates were fixed at 7% and 6 Hz and diltiazem (10(-6) M) was included in the perfusion medium, there was no effect on tissue high-energy phosphate depletion and development of VT. Even when the breakdown of ATP and the onset of VT were accelerated by isoprenaline (10(-6) M), diltiazem was not antiarrhythmic at this flow rate. Only when the coronary flow was reduced to 5% of control, in the absence and presence of isoprenaline, did diltiazem delay ventricular arrhythmias through a mechanism that was independent of changes in coronary flow and heart rate. PMID- 2913283 TI - Cholecystokinin, but not gastrin, induces gamma-aminobutyric acid release from myenteric neurons of the guinea pig ileum. AB - Effects of cholecystokinin (CCK) and gastrin on the release of acetylcholine (ACh) and gamma-aminobutyric acid (GABA) were examined in the longitudinal muscle with myenteric plexus (LM-MP) preparations of the guinea pig small intestine. CCK and gastrin induced the Ca++-dependent and tetrodotoxin-sensitive release of [3H]ACh from the LM-MP preparations preloaded with [3H]choline. Proglumide, but not scopolamine, hexamethonium and [D-Pro2,D-Trp7,9]substance P inhibited the release of [3H]ACh induced by CCK and gastrin. The desensitization to CCK and gastrin was observed with a 30-min exposure of the preparation to CCK and gastrin, respectively, and the cross-desensitization to peptides was not observed, thereby indicating that these peptides induce the release of ACh mainly via respective receptors. Bicuculline which inhibited completely the release of [3H]ACh induced by GABA inhibited the release of [3H]ACh induced by CCK but not by gastrin by 42.3 +/- 4.22%. CCK, but not gastrin, produced the Ca++-dependent and tetrodotoxin-sensitive release of endogenous GABA and [3H]GABA from LM-MP preparations preloaded with [3H]GABA. The release of [3H]GABA induced by CCK was antagonized by proglumide, but not by scopolamine, hexamethonium and [D-Pro2,D Trp7,9]substance P. These results provide evidence that the GABAergic neuron is stimulated by CCK, but not by gastrin and stimulates the cholinergic neuron. PMID- 2913284 TI - Pharmacological profile of moclobemide, a short-acting and reversible inhibitor of monoamine oxidase type A. AB - The novel antidepressant moclobemide is a reversible inhibitor of monoamine oxidase (MAO), preferentially of type A. Moclomide was active in three animal models considered predictive for antidepressant activity: 1) it prevented dose dependently akinesia and blepharospasm induced in mice and rats by Ro 4-1284, a short-acting amine releasing agent. Prevention of akinesia by moclobemide also depended upon the dose of Ro 4-1284. For comparison also, effects of cimoxatone, harmaline, tranylcypromine and clorgyline are presented: 2) in cats, it selectively and dose-dependently suppressed rapid eye movement sleep without disturbing the sleep-wakefulness cycle; and 3) in the behavioral despair test in mice, it decreased the immobility score to a similar degree as amitriptyline or imipramine. In addition, moclobemide potentiated 5-hydroxytryptophan-induced stereotypies in rats with a potency similar to cimoxatone and with a duration of action of less than 24 hr. Moclobemide had almost no effect on the spontaneous behavior in mice, rats, cats and monkeys. Only in higher doses, marginal sedation and slight impairment in motor performance were seen. Moclobemide did not prevent pilcarpine-induced salivation in mice, demonstrating the absence of anticholinergic activity. Blood pressure and heart rate of freely moving, spontaneously hypertensive rats were only slightly decreased for less than 3 hr. Moclobemide moderately potentiated the pressor effect of p.o. tyramine in rats. In conclusion, the reversible MAO inhibitor moclobemide is active in animal models sensitive to all major drugs used in the treatment of depression. In contrast to imipramine-like antidepressants, it lacks anticholinergic activity and it differs from classic MAO inhibitors by potentiating only weakly the pressor effect of p.o. tyramine. PMID- 2913285 TI - In vitro effects of ciprofloxacin and pefloxacin on growth of normal human hematopoietic progenitor cells and on leukemic cell lines. AB - The in vitro effect of ciprofloxacin and pefloxacin on growth of normal hematopoietic progenitor cells and on leukemic cell lines was investigated. Ciprofloxacin and pefloxacin caused dose-dependent inhibition of colony formation both from normal bone marrow cells and from the leukemic line K-562 cells. This inhibition exerted by ciprofloxacin and pefloxacin was statistically significant at concentrations of 25 micrograms/ml and above. Ciprofloxacin appeared to be the most potent inhibitor of colony formation among the antimicrobial agents tested. Although the inhibitory effect of pefloxacin on normal hematopoietic stem cells was similar to that of cefazolin and chloramphenicol, the inhibitory effect of pefloxacin on leukemic cells was more prominent than that of cefazolin and chloramphenicol. In a proliferation assay in liquid culture of the cell line HL 60, ciprofloxacin and pefloxacin caused a dose-dependent inhibition of cell proliferation. Both drugs failed to induce cellular differentiation, as assessed by the nitrogen blue tetrazolium dye reduction assay. In therapeutic concentrations no cumulative toxic effect of the combination of ciprofloxacin with cytosine-arabinoside, vincristine, actinomycin D and doxorubicin on colony formation by HL-60 cells was observed. It is concluded that ciprofloxacin does not exert in vitro inhibitory effect on human leukemic cells when assayed at concentrations of less than or equal to 5 micrograms/ml. However, at concentrations of 25 and 50 micrograms/ml of ciprofloxacin alone and in combination with several antineoplastic agents exerts an inhibitory effect on colony formation. PMID- 2913286 TI - Renal clearance of substituted hippurates in the dog. I. Benzoylglycine (hippurate) and methyl-substituted benzoylglycines. AB - Plasma kinetics and renal excretion of benzoylglycine (hippurate) and methyl substituted benzoylglycines were studied in three Beagle dogs, after rapid i.v. administration of about 1 g of glycine conjugate. Benzoylglycine and the 3- and 4 methyl analogs showed nonlinear plasma protein binding varying between 20 and 80% over a concentration range of 5 to 450 micrograms/ml. For 2-methylbenzoylglycine an extremely high protein binding, practically approaching 100%, was observed at low plasma levels (less than 50 micrograms/ml). All conjugates were cleared largely via the kidney (greater than 80% of the dose) and, except for the 2 methyl analog, eliminated rapidly from plasma. Plasma concentration and renal excretion rate data were analyzed simultaneously with a previously developed physiologically based kidney model. Tubular secretion appeared to be a function of the total drug concentration in renal plasma, except for 2 methylbenzoylglycine, presumably due to its tight protein binding. The average values of the parameters characterizing the tubular transport maximum (TM in milligrams per minute) and the apparent affinity for the secretory system (KT in micrograms per milliliter) were: benzoylglycine TM = 5.5 +/- 0.8, KT = 40 +/- 5; 3-methylbenzoylglycine TM = 7.1 +/- 3.3, KT = 49 +/- 1; 4-methylbenzoylglycine TM = 8.0 +/- 1.6, KT = 14 +/- 6. Secretion of 2-methylbenzoylglycine was not saturated. Accordingly, only the ratio TM/KT = 163 +/- 54 ml/min could be calculated. An interesting observation was the partial deconjugation of 4 methylbenzoylglycine to its corresponding benzoate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2913287 TI - Renal clearance of substituted hippurates in the dog. II. 4-Amino-, hydroxy- and methoxy-substituted benzoylglycines. AB - Plasma kinetics and renal excretion of 4-aminobenzoylglycine (p-aminohippurate), hydroxy- and methoxy-substituted benzoylglycines were studied in three Beagle dogs after rapid i.v. administration of about 1 g. Plasma protein binding of 4 amino-, 3-hydroxy- and 4-hydroxybenzoylglycine was low (less than 15%) and practically constant over a range of 5 to 450 micrograms/ml, whereas the 2 hydroxy analog showed concentration-dependent protein binding (40-80%). The excretory patterns of the 4-amino, 3- and 4-hydroxy analogs were essentially the same; rapid elimination from plasma into urine (greater than 80% of the dose), mainly by very efficient supply-limited tubular secretion. Conversely, the excretion of 2-hydroxybenzoylglycine was characterized by a lower plasma clearance and total renal excretion (64% of the dose), and a limited capacity of the tubular secretory system. The methoxybenzoylglycines showed nonlinear plasma protein binding varying between 10 and 70%, rapid clearance from plasma, largely by renal excretion (72-84% of the administered dose). Tubular secretion of 2- and 3-methoxybenzoylglycine was saturated, whereas complete saturation was not achieved for the 4-methoxy isomer. The kinetic parameters of tubular secretion were estimated with a physiologically based kidney model: 2-hydroxy, tubular transport maximum (TM) = 4.4 +/- 0.9 mg/min, Michael-Menten constant of the tubular secretion mechanism (KT) = 23 +/- 8 micrograms/ml; 2-methoxy-TM = 11.7 +/ 4.9 mg/min, KT = 42 +/- 9 micrograms/ml; 3-methoxy-TM = 8.8 +/- 1.0 mg/mn, KT = 27 +/- 20 micrograms/ml. Inasmuch as secretion of the other compounds was not saturated, only the intrinsic secretion clearance (CLint) = TM/KT could be estimated; 4-amino-CLint = 145 +/- 50 ml/min, 3-hydroxy-CLint = 194 +/- 21 ml/min, 4-hydroxy-CLint = 153 +/- 23 ml/min and 4-methoxy-CLint = 201 +/- 47 ml/min. The 4-methoxy isomer was metabolized to some extent by deconjugation of the glycine moiety and the resulting benzoate was found in plasma but not in urine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2913288 TI - Cardiovascular effects of cocaine: enhancement by yohimbine and atropine. AB - The cardiovascular effects of cocaine, alone and in combination with yohimbine and/or atropine, were studied in dogs anesthetized with pentobarbital sodium. All dogs were instrumented for the measurement of arterial blood pressure, left ventricular contractile force, left circumflex coronary artery blood flow, lead II ECG and heart rate. Dogs were divided into two groups; one group received no pretreatment, the other group was pretreated with atropine sulfate, 2 mg/kg. Both groups received two i.v. doses of cocaine, 1 mg/kg, approximately 3.5 hr apart. Thirty minutes before administration of the second cocaine dose, yohimbine, 0.25 mg/kg, i.v. was administered. In control animals which did not receive atropine or yohimbine, there was no difference in the cardiovascular responses to the two cocaine doses administered on this schedule. Administration of cocaine alone increased mean arterial blood pressure 9.6 +/- 2.2 mm Hg and increased the rate pressure product, an index of myocardial oxygen consumption, 12.6 +/- 4.7%. Coronary blood flow was increased 13.1 +/- 4%. Yohimbine pretreatment significantly enhanced the cardiovascular actions of cocaine and this enhancement was most pronounced in the presence of atropine. When cocaine was administered after treatment with both atropine and yohimbine, mean arterial blood pressure was increased 44.2 +/- 7.2 mm Hg, heart rate was increased 30 +/- 7.9 beats/min and the rate-pressure product was increased by 72 +/- 10.1%, whereas coronary blood flow was increased only 42.8 +/- 12%. These data suggest that presynaptic alpha adrenergic and cholinergic muscarinic blockade may significantly increase the risk of cocaine-induced cardiovascular toxicity. PMID- 2913289 TI - Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on lipid synthesis and lipogenic enzymes in the rat. AB - A single i.p. administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) caused within 1 wk of exposure a dose-dependent progressive inhibition of liver fatty acid synthetic rate with concomitant decreases in hepatic fatty acid synthetase and acetylcoenzyme A carboxylase activities. Similarly, hepatic cholesterol synthetic rate was markedly inhibited with increasing dosage of TCDD, although the corresponding decrease in 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity was of lesser magnitude. Linear regression analyses of the reciprocals of the responses versus the dose revealed that the TCDD concentration which caused 50% inhibition of the activities of various lipogenic enzymes and of lipid synthetic rates ranged from 11 to 20 micrograms/kg (34-67 nM) with an average of 15 micrograms/kg (47 nM). Hepatic cholesterol synthesis seemed to be more sensitive to inhibition than fatty acid synthesis whether it was based on TCDD dosage or duration of exposure. The degree of inhibition of all the above parameters except fatty acid synthesis in liver and adipose tissues increased from 1 to 2 wk of exposure but was less pronounced after 4 wk exposure. Significantly, the adipose tissue was found to be more sensitive than the liver with respect to inhibition of fatty acid synthesis by increasing dosage of TCDD. Thus, the biochemical mechanism of loss of adipose mass caused by TCDD exposure may well be mediated by strong inhibition of lipid synthesis in the adipose tissue coupled with increased mobilization of depot fat. PMID- 2913290 TI - Effects of experimental diabetes on biochemical and functional characteristics of bladder muscarinic receptors. AB - Bladder dysfunction is a common complication of diabetes mellitus and is attributed in part to peripheral neuropathy. We investigated the effects of experimental diabetes on muscarinic receptors in rat bladder smooth muscle, 2, 4 and 8 weeks after i.v. injection of 65 mg/kg of streptozotocin. At all time points, diabetic animals had a lower body weight, higher serum glucose levels and reduced serum insulin levels than age-matched controls. Diabetic animals had a markedly increased urine output and significant enlargement of the bladder dome. The amount of muscarinic receptor labeled with [3H]quinuclidinyl benzylate (QNB) was higher in the bladder dome of diabetic animals than control animals, whereas the affinity of the labeled antagonist for its binding sites was similar in both groups. Muscarinic agonists and antagonists inhibited [3H]QNB binding with similar inhibitory constants (Ki) in control and diabetic dome. The rank order of Ki values in inhibition of [3H]QNB binding by muscarinic agonists and antagonists: atropine less than acetylcholine less than carbachol less than AF-DX 116 = pirenzepine less than bethanechol, is consistent with the presence of M2 muscarinic receptors in the bladder dome. In functional studies, muscarinic agonists induced a larger contractile response in bladder dome muscle strips from 8-week-diabetic animals than from controls. ED50 values were similar in control and treated groups, with the rank order of ED50 values being in good agreement with the Ki values obtained from receptor binding studies, i.e., acetylcholine less than carbachol less than bethanechol. These data show a direct correlation between the diabetes-induced biochemical and functional alterations in muscarinic receptor properties of rat bladder. PMID- 2913291 TI - Synthesis and cytostatic activity of geiparvarin analogues. AB - In an attempt to determine some of the structural features of geiparvarin (1) that account for its cytostatic activity in vitro, a series of geiparvarin analogues (4a-g) modified in the 3(2H)-furanone moiety have been designed and synthesized. The preparation of 4a-g was achieved through a new approach to the 3(2H)-furanone ring based on the elaboration of isoxazole derivatives. Among these synthetic analogues, 4b, the 5-methyl-5-ethyl derivative, proved as active as 1 in inhibiting the proliferation of murine and human tumor cell lines in vitro. As a rule, substitutions at the C5 atom of the 3(2H)-furanone moiety of 1 slightly decreased the cytostatic activity of geiparvarin. Several geiparvarin analogues described in this study (i.e. the 5-methyl-5-ethyl derivative 4b, 3(2H) furanimine 4c, 5-methyl derivative 4f, and 5-ethyl derivative 4g) showed such activity in vitro and deserve further investigation for their antitumor potentials in vivo. PMID- 2913292 TI - Studies on angiotensin converting enzyme inhibitors. 4. Synthesis and angiotensin converting enzyme inhibitory activities of 3-acyl-1-alkyl-2-oxoimidazolidine-4 carboxylic acid derivatives. AB - (4S)-1-Alkyl-3-[[N-(carboxyalkyl)amino]acyl]-2-oxoimidazolidine-4- carboxylic acid derivatives (3) were prepared by two methods. Their angiotensin converting enzyme (ACE) inhibitory activities and antihypertensive effects were evaluated, and the structure-activity relationships were discussed. The dicarboxylic acids 3a-n possessing S,S,S configuration showed potent in vitro ACE inhibitory activities with IC50 values of 1.1 X 10(-8)-1.5 X 10(-9) M. The most potent compound in this series, monoester 3p, had an ID50 value of 0.24 mg/kg, po for inhibition of angiotensin I induced pressor response in normotensive rats and produced a dose-dependent decrease in systolic blood pressure of spontaneously hypertensive rats (SHRs) at doses of 1-10 mg/kg, po. PMID- 2913293 TI - Synthesis and radioprotective activity of dipeptide cysteamine and cystamine derivatives. AB - Some N-(dipeptidyl)-S-acetylcysteamine and N,N'-(dipeptidyl)cystamine salt derivatives were synthesized and evaluated as candidate radioprotector agents. Toxicity and radioprotective activity as the dose reduction factor (DRF) were determined in vivo on mice and compared to N-glycyl-S-acetylcysteamine trifluoroacetate. One of the most interesting compounds of this series was N glycylglycyl-S-acetylcysteamine trifluoroacetate (8). PMID- 2913294 TI - Carbamyl analogues of potent nicotinic agonists: pharmacology and computer assisted molecular modeling study. AB - To investigate how the substitution of NH2 for CH3 affects the activity of three, potent, semirigid nicotinic agonists, carbamyl analogues were synthesized. The carbamyl agonists were 1-methyl-4-carbamyl-1,2,3,6-tetrahydropyridine methiodide (1), 1-methyl-4-carbamylpiperidine methiodide (2), and 1-methyl-4 carbamylpiperazine methiodide (3). Their potencies (reciprocals of the equipotent molar ratios) at the frog neuromuscular junction with reference to carbamylcholine were 0.77, 0.052, and 0.15, respectively. The acetyl analogues were more potent by factors of 65, 175, and 17, respectively. Explanations for this variable reduction in activity were sought by using computer-assisted molecular mechanics and calculations of electrostatic potential contours. Bioactive conformations of 1-3 were assigned on the basis of a well-supported pharmacophore and the ground-state conformation of the highly potent (50 times that of carbamylcholine) prototype, isoarecolone methiodide (4). Agonist 3 and its acetyl analogue superimposed closely in their ground-state, bioactive conformations, and the differences in their electrostatic potential contours were the least among the three pairs. Accordingly, their potencies differed the least. Agonists 1 and 2 both showed greater differences (with respect to their acetyl analogues) in their electrostatic potential contours and greater differences in potency. Agonist 2, in addition, could achieve the bioactive conformation only at the expense of 2.8 kcal mol-1, and, correspondingly, its activity relative to its acetyl analogue was lowest of all. PMID- 2913295 TI - Selective thyromimetics. Cardiac-sparing thyroid hormone analogues containing 3' arylmethyl substituents. AB - Introduction of specific arylmethyl groups at the 3'-position of the thyroid hormone 3,3',5-triiodo-L-thyronine (T3), and its known hormonally active derivatives, gives liver-selective, cardiac-sparing thyromimetics, with potential utility as plasma cholesterol lowering agents. Selectivity-conferring 3' substituents include substituted benzyl, e.g. p-hydroxybenzyl, and heterocyclic methyl, e.g. 2-oxo-1,2-dihydropyrid-5-ylmethyl and 6-oxo-1,6-dihydropyridazin-3 ylmethyl. Correlations between in vivo and in vitro receptor binding affinities show that liver/heart selectivity does not depend on receptor recognition but on penetration or access to receptors in vivo. QSAR studies of the binding data of a series of 20 3'-arylmethyl T3 analogues show that electronegative groups at the para position increase both receptor binding and selectivity in vivo. However, increasing 3'-arylmethyl hydrophobicity increases receptor binding but reduces selectivity. Substitution at ortho and meta positions reduces both binding and selectivity. Replacement of the 3,5-iodo groups by halogen or methyl maintains selectivity, with 3,5-dibromo analogues in particular having increased potency combined with oral bioavailability. Diphenyl thioether derivatives also have improved potency but are less orally active. At the 1-position, the D enantiomer retains selectivity, but removal of the alpha-amino group to give a propionic acid results in loss of selective thyromimetic activity. PMID- 2913296 TI - Cardiotonic agents. 1-Methyl-7-(4-pyridyl)-5,6,7,8-tetrahydro-3 (2H) isoquinolinones and related compounds. Synthesis and activity. AB - A series of 1-methyl-7-(4-pyridyl)-5,6,7,8-tetrahydro-3(2H)-isoquinolinones and related compounds were synthesized and evaluated for positive inotropic activity. Most members of this series exerted a dose-dependent increase in myocardial contractility in the dog acute heart failure model, whereas they caused only slight changes in heart rate and blood pressure. Several derivatives, especially those with cyano, acetyl, and ethyl substituents at the 4-position, were more potent than milrinone, which was used as a reference. 4-Acetyl-1-methyl-7-(4 pyridyl)-5,6,7,8-tetrahydro-3(2H)-isoquinolinone (MS-857) is one of the most potent positive inotropic agents in this series. PMID- 2913297 TI - Syntheses and biological activities of 13-substituted avermectin aglycons. AB - The reactions of sulfonate esters of the allylic/homoallylic 13-alcohol of 5-O (tert-butyldimethylsilyl)-22,23-dihydroavermectin B1a aglycon (1a) were investigated. Nucleophilic substitution gave 13 beta-chloro and 13 beta-iodo derivatives, while solvolytic reaction conditions yielded 13 alpha-methoxy, 13 alpha-fluoro, and 13 alpha-chloro products. A mixture of 13 alpha- and 13 beta fluorides was obtained upon reaction with DAST. The 13 beta-iodide gave, upon elimination with lutidine, the 8(9),10(11),12(13),14(15)-tetraene. The 13 beta alcohol and the rearranged 15-ol 13(14)-ene and 15-amino 13(14)-ene derivatives were obtained by substitution via the allylic carbonium ion. MEM ethers 11 and 12 of the two epimeric 13-ols were prepared by alkylation with MEM chloride. In contrast, methylation of 1a with MeI and Ag2O in CH2Cl2 occurred exclusively at the tertiary 7-hydroxy group and not at the secondary 13 alpha-ol. Oxidation of the allylic alcohol 1a proceeded under Swern conditions but not with MnO2 to the 13-oxo aglycon, which was reduced by NaBH4 exclusively to the natural 13 alpha ol, while reductive amination with NaCNBH3-NH4OAc gave the 13 alpha-amine. The methoxime derivative was obtained in the form of the two geometric isomers. Anthelmintic activities against the sheep nematode Trichostrongylus colubriformis, miticidal activities against the two-spotted spider mite (Tetranychus urticae), and insecticidal activities against the southern armyworm (Spodoptera eridania) as well as the binding constants to a free living nematode (Caenorhabditis elegans) derived receptor assay were obtained and compared to avermectin B1a, 22,23-dihydroavermectin B1a, and the 13-deoxy-22,23 dihydroavermectin B1 aglycon related to the milbemycins. None of the newly prepared derivatives exceeded the potency of the three reference compounds. Lipophilic 13-substituents such as halogen, alkoxy, and methoxime retained high biological activities in all assays, while the more polar substituents hydroxy and amino had weaker activities. Rearranged 15-substituted 13(14)-ene derivatives were completely inactive. The 13-oxo and the 12,13-dehydro analogues were only weakly active in vivo despite having good binding affinity to the receptor, possibly due to instability or poor absorption. PMID- 2913298 TI - Solid-phase synthesis of 16 potent (selective and nonselective) in vivo antagonists of oxytocin. AB - We describe the synthesis and some pharmacological properties of 16 new in vivo antagonists of oxytocin. These are based on modifications of three peptides: A, B, and C. A is our previously reported potent and selective antagonist of the vasopressor (V1 receptor) responses to arginine-vasopressin (AVP)/weak oxytocin antagonist, [1-(beta-mercapto-beta,beta-pentamethylenepropionic acid), 2-O methyltyrosine]arginine-vasopressin (d(CH2)5[Tyr(Me)2]AVP. B reported here, the Ile3 analogue of A, is d(CH2)5[Tyr(Me)2]AVT (5 below) and C is our previously reported potent nonselective oxytocin antagonist/AVP V1 antagonist, [1-(beta mercapto-beta,beta-pentamethylenepropionic acid),2-O- methyltyrosine,8 ornithine]vasotocin (d(CH2)5[Tyr(Me)2]OVT). The following substitutions and deletions, alone or in combination, were employed in A, B, and C: 1 deaminopenicillamine (dP); D-Tyr(Alk)2 (where Alk = Me or Et), D-Phe2; Val4, Thr4; delta 3-Pro7; Lys8, Cit8; desGly9, desGly-NH2(9), Ala-NH2(9); Leu-NH2(9); Arg-NH2(9). The 16 new analogues are (1) d(CH2)5[D-Tyr(Me)2]AVP, (2) d(CH2)5[D Tyr(Me)2, Val4,delta 3-Pro7]AVP, (3) d(CH2)5[D-Tyr-(Et)2, Val4,Lys8]VP, (4) d(CH2)5[D-Tyr(Et)2,Val4,Cit8]VP, (5) d(CH2)5[Tyr(Me)2]AVT, (6) d(CH2)5[Tyr(Me)2,Lys8]VT, (7) dP[Tyr(Me)2]AVT, (8) dP[Tyr(Me)2,Val4]AVT, (9) d(CH2)5[D-Tyr(Me)2, Val4]AVT, (10) d(CH2)5[D-Phe2,Val4]AVT, (11) d(CH2)5[Tyr(Me)2,Thr4]OVT, (12) d(CH2)5[Tyr(Me)2,Thr4,Ala-NH2(9)]OVT, (13) d(CH2)5[Tyr(Me)2,Thr4,Leu-NH2(9)]OVT, (14) d(CH2)5[Tyr(Me)2,Thr4,Arg-NH2(9)]OVT, (15) desGly-NH2(9),d(CH2)5[Tyr(Me)2,Thr4]OVT, (16) desGly9,d(CH2)5[Tyr(Me)2,Thr4]OVT. 1-4 are analogues of A, 5-10 are analogues of B, and 11-16 are analogues of C. Their protected precursors were synthesized either entirely by the solid-phase method or by a combination of solid-phase and solution methods (1 + 8 or 8 + 1 couplings). All analogues were tested in rats for agonistic and antagonistic activities in oxytocic (in vitro, without and with Mg2+, and in vivo) assays as well as by antidiuretic and vasopressor assays. All analogues exhibit potent oxytocic antagonism in vitro and in vivo. With an in vitro pA2 (in the absence of Mg2+) = 9.12 +/- 0.09, dP[Tyr(Me)2]AVT is (7) one of the most potent in vitro oxytocin antagonists reported to date. Fifteen of these analogues (all but 6) appear as potent or more potent in vivo oxytocin antagonists than C (pA2 = 7.37 +/- 0.17). Analogues 1-9 and 14 are potent AVP V1 antagonists. Their anti-V1 pA2 values range from 7.92 to 8.45. They are thus nonselective oxytocin antagonists.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2913299 TI - Potential antitumor agents. 57. 2-Phenylquinoline-8-carboxamides as "minimal" DNA intercalating antitumor agents with in vivo solid tumor activity. AB - A series of phenyl-substituted derivatives of the "minimal" DNA-intercalating agent N-[2-(dimethylamino)-ethyl]-2-phenylquinoline-8-carboxamide (1) have been synthesized and evaluated for in vivo antitumor activity, in a continuing search for active compounds of this class with the lowest possible DNA association constants. Substitution on the 2'-position of the phenyl ring gave compounds of lower DNA binding ability that did not intercalate DNA, indicating that it is necessary for the phenyl ring to be essentially coplanar with the quinoline for intercalative binding. An extensive series of 4'-substituted derivatives was evaluated, but there was no overall relationship between biological activity and substituent lipophilic or electronic properties. However, several compounds showed good solid tumor activity, with the 4'-aza derivative 18 being clearly superior to the parent compound, effecting about 50% cures in both leukemia and solid tumor models. PMID- 2913300 TI - Synthesis, cytotoxicity, and antiviral activity of some acyclic analogues of the pyrrolo[2,3-d]pyrimidine nucleoside antibiotics tubercidin, toyocamycin, and sangivamycin. AB - A number of 7-[(1,3-dihydroxy-2-propoxy)methyl]pyrrolo[2,3d-d]pyrimidine derivatives that are structurally related to toyocamycin and sangivamycin and the seco nucleosides of tubercidin, toyocamycin, and sangivamycin were prepared and tested for their biological activity. Treatment of the sodium salt of 4-amino-6 bromo-5-cyanopyrrolo[2,3-d]-pyrimidine with 1,3-bis(benzyloxy)-2-propoxymethyl chloride afforded compound 3, which without isolation was debrominated to obtain 4-amino-5-cyano-7-[[1,3-bis(benzyloxy)-2- propoxy]methyl]pyrrolo[2,3 d]pyrimidine. Although catalytic hydrogenolysis failed, the benzyl ether functionalities of 4 were successfully cleaved by boron trichloride to afford 4 amino-5-cyano-7-[(1,3-dihydroxy-2- propoxy)methyl]pyrrolo[2,3-d]pyrimidine. Conventional functional group transformation of the cyano group of 6 provided a number of novel 5-substituted derivatives. Tubercidin (8a), toyocamycin (8b), and sangivamycin (8c) were treated separately with sodium metaperiodate and then with sodium borohydride to afford the 2',3'-seco derivatives 9a-c, respectively. The acyclic nucleoside 4-chloro-2-(methylthio)-7-[[1,3-bis(benzyloxy)-2- propoxy]methyl]pyrrolo[2,3-d]pyrimidine was aminated, desulfurized with Raney Ni, and then debenzylated to provide the tubercidin analogue 11. Cytotoxicity evaluation against L1210 murine leukemic cells in vitro showed that although the parent compounds tubercidin (8a), toyocamycin (8b), and sangivamycin (8c) were very potent growth inhibitors, the acyclic derivatives 6, 7a-c, and 9a-c had only slight growth-inhibitory activity. Evaluation of compounds 6, 7a, 7b, 7c, 9a, 9b, 9c, 11 for cytoxicity and activity against human cytomegalovirus (HCMV) and herpes simplex virus type 1 (HSV-1) revealed that only the carboxamide (7a) and the thioamide (7c) were active. Compound 7c was the more potent of the two, inhibiting HCMV but not HSV-1 at concentrations producing little cytotoxicity. PMID- 2913301 TI - Synthesis, tubulin binding, antineoplastic evaluation, and structure-activity relationship of oncodazole analogues. AB - In an attempt to identify a soluble oncodazole analogue that could be easily formulated, a series of substituted oncodazoles was synthesized and evaluated for tubulin binding affinity, in vitro cytotoxicity against cultured mouse B-16 cells, and ability to prolong lifespan at the maximally tolerated dose in the P388 mouse leukemia model. Biological evaluation of all the isomeric methyloncodazoles demonstrated the thiophene 4'-position to be the only site of significant bulk tolerance, although substitution of this position with polar or charged functional groups abolished biological activity. Simple esters of the 4' carboxymethyloncodazole were shown to have enhanced antitumor activity and tubulin binding affinity relative to oncodazole. Despite a failure of this study to identify a water-soluble oncodazole with antitumor activity, the structure activity relationship developed led to a derivative with enhanced activity in the P388 leukemia model and facilitated the preparation of a biologically active photolabile analogue. PMID- 2913302 TI - Studies on hindered phenols and analogues. 1. Hypolipidemic and hypoglycemic agents with ability to inhibit lipid peroxidation. AB - A series of hindered phenols were investigated as hypolipidemic and/or hypoglycemic agents with ability to inhibit lipid peroxidation. 1,3 Benzoxathioles (9 and 22), phenoxypentanoic acid (34), phenoxypentanol (35a), phenoxynonanol (35b), phenylchloropropionic acid having a chromanyl group (25), and a thiazolidine compound (27) derived from 25, all having a hindered phenol group, were prepared and examined. Compound 27 showed the expected biological properties in vivo and in vitro without any liver weight increase. Biological activities of the analogous thiazolidine compounds, 43-58, were compared. Thus, (+/-)-5-[4-[(6-hydroxy-2,5,7,8-tetramethylchroman-2-yl)methoxy]- benzyl]-2,4 thiazolidinedione (27) (CS-045) was found to have all of our expected properties and was selected as a candidate for further development as a hypoglycemic and hypolipidemic agent. PMID- 2913303 TI - Studies on bioactive compounds. 13. Synthesis and lack of growth-inhibitory properties of cyclohexane-1,2,4-triol 1,2-diesters, which resemble ring C of the phorbol ester molecule. AB - It has been suggested that ring C of biologically active phorbol esters is an essential structural feature of the pharmocophore which confers activity on these compounds. In this study the hypothesis has been tested that compounds which resemble ring C of the phorbol ester molecule mimic the ability of phorbol esters to inhibit cell growth at nontoxic concentrations. All four diastereoisomers of (+/-)-1,2-di-O-octanoylcyclohexane-1,2,4-triol have been prepared from cyclohexen 4-ol and tested for growth-inhibitory and cytotoxic properties. The phorbol ester 12-O-tetradecanoylphorbol 13-acetate inhibited the growth of A549 human lung carcinoma cells by 50% at a concentration of 0.2 nM and exerted cytotoxicity at concentrations of greater than 1 microM. Diacylglycerols are the physiological ligands and activators of protein kinase C, the receptor via which phorbol esters are thought to mediate their effects. The diacylglycerols 1-oleoyl-2 acetylglycerol and 1,2-dioctanoylglycerol and the cyclohexanetriol diesters inhibited the growth of A549 cells only at concentrations of 10(-5) to 10(-4) M, at which they were also cytotoxic. A computer-assisted analysis of the goodness of fit between the cyclohexanetriol diesters and ring C of the phorbol moiety revealed possible energetic grounds for conformational dissimilarities. The results suggest that activation of protein kinase C alone is probably not sufficient to reproduce phorbol ester induced growth arrest in A549 cells and that the cyclohexanetriol diesters may lack pivotal elements of the phorbol ester pharmacophore. PMID- 2913304 TI - New brain perfusion imaging agents based on 99mTc-bis(aminoethanethiol) complexes: stereoisomers and biodistribution. AB - In developing new brain perfusion imaging agents, we prepared 99mTc complexes of racemic mixtures of bis(aminoethanethiol) (BAT) derivatives containing an N' benzylpiperazinyl (BPA) side chain. Due to the presence of a chiral center, a mixture of diastereomers (syn and anti) following chelation with the 99mTc (no carrier-added) was obtained. The neutral and lipid-soluble 99mTc-BPA-BAT (99mTc, T1/2 = 6 h) isomers were separated. The syn and anti isomers of carrier-added 99Tc-BPA-BAT (99Tc, T1/2 = 2 x 10(5) years) were also synthesized, separated, and crystallized. The X-ray crystallography of 99Tc-BPA-BAT showed the syn and anti conformations (in relationship with the central TC(=O)N2S2 core). Despite a similarity in the partition coefficients for the two isomers, the syn isomer showed a higher in vivo brain uptake and longer brain retention in rats (2.77 and 1.08% dose/organ at 2 and 15 min) than that of the corresponding anti isomer (0.57 and 0.27% dose/organ at 2 and 15 min). This information is important and should be taken into consideration when new 99mTc-labeled brain perfusion imaging agents are being designed. PMID- 2913305 TI - Synthesis and structure-activity studies of some disubstituted phenylisoxazoles against human picornavirus. AB - A number of 2,6-disubstituted analogues of disoxaril, a broad spectrum antipicornavirus agent, have been prepared and evaluated against several rhinovirus serotypes. A QSAR study revealed that the mean MIC (MIC) against five rhinovirus serotypes correlated well with log P. The 2,6-dichloro analogue, 15, was highly effective in vitro against rhinoviruses with an MIC80 of 0.3 microM, as well as against several enteroviruses, and was also effective in preventing paralysis in mice infected with coxsackievirus A-9. PMID- 2913306 TI - Synthesis and evaluation of antileukemic activity of 5-thienyl- or 5-(2-furyl) 2,3-dihydro-6,7-bis(hydroxymethyl)-1H-pyrrolizine bis(alkylcarbamates) and derivatives. AB - Treatment of N-(2-furoyl)proline or N-thenoylprolines and N-(2 thenoyl)thiazolidine-4-carboxylic acid with acetic anhydride and dimethyl acetylenedicarboxylate gave 5-substituted derivatives of dimethyl 2,3-dihydro-1H pyrrolizine-6,7-dicarboxylate and derivatives of dimethyl 5-(2 thienyl)pyrrolo[1,2-c]thiazole. Reduction of 2 with lithium aluminum hydride gave the diols 3a, 3b, 3c and 3d. These diols yielded the corresponding diacetates 4 by treatment with acetic anhydride. The bis(methylcarbamates) 5a, 5b, 5c, and 5d and bis(isopropylcarbamates) 6b and 6c are obtained with the appropriate isocyanates. The 1-substituted pyrrolizines were synthesized, the 1-acetoxy compounds 7b and 7c further transformed into 1-hydroxy and 1-oxo analogues. The action of hydrochloric acid on 1-acetoxy derivatives gave 3H-pyrrolizines. Evaluation of antileukemic activity was investigated on the leukemia L1210 in vivo, on several bis(alkylcarbamates). The compounds 5c and 5d show good antileukemic activity comparable with the mitomycin. PMID- 2913307 TI - Potent angiotensin II antagonists with non-beta-branched amino acids in position 5. AB - Amino acids with lipophilic side chains that contain more than one functional group on the beta-carbon, i.e. a beta-branched hydrocarbon moiety, are required in position 5 of angiotensin II (AII) analogue with potent agonist activity. This requirement for agonist activity does not follow for AII analogues with potent antagonist activity. Straight-chain amino acids may be substituted into position 5 of [Sar1,X5,Ile8]AII with retention or enhancement of antagonist activity, e.g. (X5,pA2 rabbit aorta) Phe, 9.15; Tyr, 9.6; His, 9.0; Glu,9.0; Nle, 8.85, compared to Ile, 9.1. beta-Branched side chains can still enhance the antagonist activities of [Sar1,X5,Ile8]AII analogues, e.g. X5 = (beta Me)Phe, pA2 = 9.3. An X-ray crystal structure of the Boc-(beta Me)Phe DCHA salt, prepared for the synthesis of [Sar1,-(beta Me)Phe5, Ile8]AII, revealed an S,S configuration of alpha- and beta-carbon atoms. Contrary to previous literature reports, chemical nonequivalence of the deta-protons of Pro was observed in the 1H NMR spectra of [Sar1,X5,Ile8]AII analogues bearing both beta-branched X5 side chains (X5 = Ile) and non-beta-branched X5 side chains (X5 = Ala, His). PMID- 2913308 TI - Conformationally restricted and conformationally defined tyramine analogues as inhibitors of phenylethanolamine N-methyltransferase. AB - In a search for a selective inhibitor for the epinephrine synthesizing enzyme phenylethanolamine N-methyltransferase (PNMT; EC 2.1.1.28), phenolic 2 aminotetralins (12-15 as conformationally restricted analogues of tyramine) and phenolic benzobicyclo[3.2.1]octylamines (22-24 as conformationally defined analogues of tyramine) were used to gain information about the binding interactions of the catecholic hydroxyl groups in the natural substrate norepinephrine at the active site of PNMT. In addition, these analogues provided information about the effects of conformational flexibility on active-site interaction of the aminoethyl side chain in phenolic phenylethylamines that may aid in learning the manner in which norepinephrine binds at the active site of PNMT. Analogues 22-24 were synthesized by a nine-step sequence, in which a Friedel-Crafts type intramolecular cyclization was the key step in the construction of the benzobicyclo[3.2.1]octane skeleton. p-Tyramine (10, Ki = 294 microM) was more potent than phenylethylamine (1, Ki = 854 microM) but m-tyramine (9, Ki = 1250 microM) was less potent than phenylethylamine as an inhibitor of PNMT. Similarly, in the conformationally restricted and conformationally defined tyramine analogues (12-15 and 22-24, respectively), the analogues with the p tyramine moiety (14, Ki = 4.7 microM; 23, Ki = 111 microM) bind to PNMT better than do the corresponding unsubstituted compounds (16, Ki = 6.8 microM; 25, Ki = 206 microM) while the analogues with the m-tyramine moiety (13, 15, 22, and 24) have a lower binding affinity than do 16 and 25. The greatly enhanced activity of the phenolic 2-aminotetralins (12-15) compared with m- and p-tyramine (9 and 10, respectively) is likely due to the restriction of the side-chain conformation. The conformationally defined analogues 22-24 were less active than the conformationally restricted ones, 12-15, although the low-energy half-chair conformation of 2-aminotetralin is defined in 22-24. The reduced activity of 22 24 compared with the activity of 12-15 is probably due to the steric hindrance from the extra bridging atoms in binding to PNMT. The interaction of the p hydroxyl group of the tyramine moiety may involve hydrogen bonding since the corresponding methyl ethers show a greatly reduced affinity for the active site of PNMT (Ki = 34 and 389 microM for methoxy analogues 28 and 35, compared to Ki = 4.7 and 111 microM for the corresponding phenolic analogues 14 and 23). PMID- 2913309 TI - Synthesis and copper-dependent antimycoplasmal activity of 1-amino-3-(2 pyridyl)isoquinoline derivatives. 2. Amidines. AB - In our search for new compounds with antimycoplasmal activity, a series of aromatic amidines derived from 1-amino-3-(2-pyridyl)isoquinoline (1) was synthesized. In the presence of 40 microM copper the most active compounds show growth inhibition of Mycoplasma gallisepticum in the nanomolar range. These compounds are 3 times as active as tylosin, an antimycoplasmal therapeutic agent that is used in veterinary practice. In the presence of copper, amidines derived from 1 are 2-3 times more active than the corresponding amides. Furthermore it was established that for these compounds too, the presence of a 2,2'-bipyridyl moiety is a necessary prerequisite for antimycoplasmal activity. As for the amides, antimycoplasmal activity of amidines derived from 1 is dependent on the hydrophobic fragmental value of the aromatic nucleus of the amidine moiety. A quantitative structure-activity relationship established the optimal hydrophobic fragmental value of this part of the molecule to be zero. PMID- 2913310 TI - Quaternary salts of 2-[(hydroxyimino)methyl]imidazole. 2. Preparation and in vitro and in vivo evaluation of 1-(alkoxymethyl)-2-[(hydroxyimino)methyl]-3 methylimida zolium halides for reactivation of organophosphorus-inhibited acetylcholinesterases. AB - A series of structurally related mono- and bis-1,3-disubstituted 2 [(hydroxyimino)methyl]imidazolium halides were evaluated in vitro for their ability to reactivate electric eel, bovine, and human erythrocyte (RBC) acetylcholinesterases (AChE) inhibited by ethyl p-nitrophenyl methylphosphonate (EPMP) and 3,3-dimethyl-2-butyl methyl-phosphonofluoridate (soman, GD). All new compounds were characterized for (hydroxyimino)methyl acid dissociation constant, nucleophilicity, octanol-buffer partition coefficient, reversible AChE inhibition, and kinetics of reactivation of EPMP-inhibited AChEs. For GD inhibited AChEs, maximal reactivation was used to compare compounds since rapid phosphonyl enzyme dealkylation "aging" complicated interpretation of kinetic constants. For comparison, we also evaluated three known pyridinium therapeutics, 2-PAM, HI-6, and toxogonin. In vivo evaluation in mice revealed that when selected imidazolium compounds were coadministered with atropine sulfate, they were effective in providing lifesaving protection against both GD and EPMP challenges. This was a major accomplishment in the search for effective anticholinesterase therapeutics--the synthesis and preliminary evaluation of the first new monoquaternary soman antidotes with potencies superior to 2-PAM. Significantly, there was an apparent inverse relationship between in vitro and in vivo results; the most potent in vivo compounds proved to be the poorest in vitro reactivators. These results suggested that an alternative and possibly novel antidotal mechanism of protective action may be applicable for the imidazolium aldoximes. Selected compounds were also evaluated for their inhibition of AChE phosphorylation by GD and antimuscarinic and antinicotinic receptor blocking effects. PMID- 2913311 TI - Quaternary salts of 2-[(hydroxyimino)methyl]imidazole. 3. Synthesis and evaluation of (alkenyloxy)-, (alkynyloxy)-, and (aralkyloxy)methyl quaternarized 2-[(hydroxyimino)methyl]-1-alkylimidazolium halides as reactivators and therapy for soman intoxication. AB - A series of structurally related monosubstituted 1-[(alkenyloxy)methyl]-, 1 [(alkynyloxy)methyl]-, and 1-[(aralkyloxy)methyl]-2-[(hydroxyimino)methyl]-3 methyli midazolium halides were prepared and evaluated. All new compounds were characterized with respect to (hydroxyimino)methyl acid dissociation constant, nucleophilicity, and octanol-buffer partition coefficient. The alkynyloxy substituted compounds were also evaluated in vitro with respect to reversible inhibition of human erythrocyte (RBC) acetylcholinesterase (AChE) and kinetics of reactivation of human AChE inhibited by ethyl p-nitrophenyl methylphosphonate (EPMP). In vivo evaluation in mice revealed that coadministration of alkynyloxy substituted imidazolium compounds with atropine sulfate provided significant protection against a 2 x LD50 challenge of GD. For the alkynyloxy-substituted imidazolium drugs there is a direct relationship between in vitro and in vivo activity: the most potent in vivo compounds against GD proved to be potent in vitro reactivators against EPMP-inhibited human AChE. These results differ from the observations made on the sterically hindered imidazolium compounds (see previous article) and suggest that several antidotal mechanisms of protective action may be applicable for the imidazolium aldoxime family of therapeutics. The ability of the alkynyloxy substituents to provide life-saving protection against GD intoxication was not transferable to the pyridinium or triazolium heteroaromatic ring systems. PMID- 2913312 TI - Coaggregation of black-pigmented Bacteroides species with other oral bacteria. AB - Coaggregation of Bacteroides gingivalis and other black-pigmented bacteroides with several oral bacteria was studied with "reagent" strains specially prepared by methods that have been described previously. B. gingivalis coaggregated with Veillonella, Capnocytophaga and Actinomyces spp., but not with any Streptococcus spp. Coaggregation of B. gingivalis with other bacteria was inhibited and reversed by lactose. Of the asaccharolytic black-pigmented bacteroides, only B. gingivalis demonstrated any coaggregation with other bacteria, whereas within the saccharolytic species, B. loescheii showed a marked ability to coaggregate with several species of oral bacteria. This property of coaggregation by B. gingivalis may be an important factor in the pathogenesis of periodontal infections. PMID- 2913313 TI - A new methicillin- and gentamicin-resistant Staphylococcus aureus in Dublin: molecular genetic analysis. AB - In June 1985 two new strains of methicillin- and gentamicin-resistant Staphylococcus aureus (MGRSA) were isolated in a Dublin hospital. Of these, one strain spread rapidly, affecting a total of 65 patients during the following 18 months, and subsequently spread to a second Dublin hospital. Detailed laboratory studies, including plasmid screening, plasmid restriction enzyme digest pattern analysis, hybridisation analysis, location of resistance determinants, and bacteriophage typing with a set of experimental S. aureus typing phages, demonstrated that the "new" MGRSA organisms, termed Phenotype III Dublin isolates, were completely distinct from, and unrelated to, the MGRSA strains responsible for serious nosocomial infections in Dublin hospitals during the decade before June 1985. These Phenotype III isolates were very similar to MGRSA organisms isolated in a Baghdad hospital during 1984. Data from plasmid curing, plasmid transfer and hybridisation experiments indicated that 20% of the Phenotype-III isolates expressed chromosomally encoded, high level resistance to ethidium bromide (MIC 120 micrograms/ml), and that this was possibly due to chromosomal integration of a penicillinase-like plasmid. PMID- 2913314 TI - Characterisation of methicillin-resistant isolates of Staphylococcus aureus by analysis of whole-cell and exported proteins. AB - Thirty-four isolates of methicillin-resistant Staphylococcus aureus (MRSA) from patients in Glasgow Royal Infirmary were studied. Whole-cell protein profiles obtained by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) were compared with banding patterns produced by immunoblots of exported proteins. Human plasma was used as a source of staphylococcal antibodies for the immunoblots. SDS-PAGE of whole-cell extracts did not usefully distinguish different isolates of MRSA. Reproducible banding patterns were obtained by immunoblots of exported proteins. Analyses of immunoblots by use of the Dice coefficient demonstrated that isolates of MRSA could be divided into two main groups. Immunoblots of exported proteins provided a rapid, reproducible and sensitive method for characterisation of MRSA. PMID- 2913315 TI - Rapid identification of Vibrio cholerae serotype O1 from primary isolation plates by a coagglutination test. AB - A coagglutination test was developed for identifying suspected colonies of Vibrio cholerae serotype O1 directly from primary isolation plates. Visible agglutination occurs when V. cholerae O1 antibody attached to cell-wall protein A of Staphylococcus aureus reacts with its homologous antigen. From 314 faecal samples from clinically suspected cases of cholera, 210 colonies from thiosulphate citrate bile salts sucrose (TCBS) agar and 222 colonies from taurocholate tellurite gelatin (TTG) agar were tested as suspect V. cholerae. In each case 204 isolates were identified as V. cholerae O1 by conventional methods and also gave positive results for V. cholerae O1 in the coagglutination test; with one partial exception, no other colonies tested gave positive results. The coagglutination test is simple and inexpensive and provides a result 24 h earlier than conventional methods. PMID- 2913316 TI - Cytotoxic activity of crude extracts of Bacteroides gingivalis. AB - The cytotoxic activities of culture supernates, crude cell extracts and cell-wall materials of Bacteroides gingivalis were investigated in vitro. Each component was cytotoxic to Vero cells and, to a lesser extent, Wi 38 cells. The cytotoxic agents had similar effects on the cell lines to butyric acid, propionic acid and a partially-purified trypsin-like protein extracted from a clinical isolate of B. gingivalis; the effects were eliminated by heat. Cytotoxic materials obtained from young cultures were more susceptible to heat than those from older cultures. The heart-labile substance inside and outside the bacterial cell in young cultures of B. gingivalis may contribute to its overall cytotoxic activity. PMID- 2913317 TI - Updated recommendations for ophthalmic practice in relation to the human immunodeficiency virus. PMID- 2913318 TI - Retinoblastoma. Case report. PMID- 2913319 TI - Parents and cataract kids. Supporting the family to treat the child. PMID- 2913320 TI - Computer applications in an ophthalmic practice. PMID- 2913321 TI - Personal action needed to win cancer war, NCAB says. PMID- 2913322 TI - In laboratory research, yesterday's visions are today's tools--and they are expensive. PMID- 2913323 TI - The pill and breast cancer: is there a connection? PMID- 2913324 TI - Cell proliferation kinetics and multistage cancer risk models. AB - Cell-kinetic multistage (CKM) cancer-risk models account for clonal proliferation of postulated intermediate (initiated, premalignant) cell populations during tumorigenesis. To date, almost all CKM models considered have assumed that intermediate, premalignant cells may proliferate exponentially over time in vivo. This "exponential growth" assumption, however, may not always be as biologically plausible as the alternative assumption that cells tend to grow geometrically in time. The general CKM model and applications of it that presume exponential cell growth are reviewed here. Geometric CKM models are then considered, previous erroneous analyses of these models are reviewed, and a corrected mathematical treatment is provided. It is pointed out that the presumption of exponential instead of geometric proliferation kinetics may lead to underestimates of small increments in CKM-predicted cancer risk above background if the geometric assumption is true. An evaluation of pertinent biological evidence is provided, which indicates that precancerous cells may typically proliferate geometrically. Consequently, if CKM models are used for environmental risk assessment, it may be prudent for one to presume geometric cell growth unless specific data support an alternative assumption. PMID- 2913325 TI - Calorie-providing nutrients and risk of breast cancer. AB - A case-control study was conducted in Italy to investigate the role of diet in breast cancer. Cases were 250 women with breast cancer, and controls were a stratified random sample of 499 women from the general population. A dietary history questionnaire was used to measure the intake of total fat, saturated fat, animal proteins, and other macronutrients. In multivariate analyses, the relative risks of breast cancer for women in the highest quintile of consumption of saturated fat and animal proteins were 3.0 (95% confidence interval, 1.9-4.7) and 2.9 (1.8-4.6), respectively. A reduced risk was found for women who derived less than 28% of calories from fat versus greater than 36%. A similarly reduced risk was found for women who derived less than 9.6% of calories from saturated fat or less than 5.9% from animal proteins. These data suggest that during adult life, a reduction in dietary intake of fat and proteins of animal origin may contribute to a substantial reduction in the incidence of breast cancer in population subgroups with high intake of animal products. PMID- 2913326 TI - Improved detection of allele loss in renal cell carcinomas after removal of leukocytes by immunologic selection. AB - We used immunologic selection to remove contaminating leukocytes from primary renal cell carcinomas and to improve detection of chromosome 3p allele loss. Leukocytes were removed from disaggregated renal cell carcinomas by a double antibody, magnetic bead separation technique. Before immunologic selection, the preparations contained 26% +/- 15% (SD) tumor cells (n = 7); after immunologic selection, the preparations contained 76% +/- 12% tumor cells. The recovery of tumor cells in the purified preparations was about 10%. Detection of allele deletion was facilitated by immunologic selection. This method may be useful in allele deletion analysis of other human solid tumors that are contaminated with host leukocytes and, with appropriate modification, may be applied to tumors that are contaminated with other cell types. PMID- 2913327 TI - Adenovirus type 9-induced tumorigenesis in the rat mammary gland related to sex hormonal state. AB - Adenovirus type 9 was inoculated sc into newborn Wistar/Furth rats, divided into four groups: (1) six male rats, not treated further; (2) 11 male rats, castrated at 4 weeks of age; (3) 12 male rats, castrated at 4 weeks of age and subsequently treated repeatedly with estrogen; and (4) 12 female rats, not treated further. All of the rats in group 3 developed mammary hyperplasia and tumors (fibroadenomas and lipomas), in some cases with malignant histologic structure. Rats in group 4 developed similar mammary tumors, but with later appearance and significantly slower growth. A fifth group of rats, not virus inoculated but castrated and estrogen treated as in group 3, did not develop any demonstrable mammary lesions. The results show that the effects of the virus on the mammary gland are dependent upon an estrogenic background, which by itself cannot cause tumor development in males. It is suggested that viral DNA is incorporated into the cellular DNA in such a way that it influences the synthesis and/or activity of steroid receptors, triggering tumor development. PMID- 2913328 TI - Infused L-histidinol and cisplatin: schedule, specificity, and proliferation dependence. AB - The dose and schedule requirements found for the combination of L-histidinol and 5-fluorouracil (5-FU) were concordant with those for the combination of L histidinol and cisplatin. Furthermore, cisplatin-L-histidinol was active against colon 26 tumor, an adenocarcinoma that developed in a BALB/c female mouse and that has been grown as a solid tumor. The toxicity of cisplatin was prevented only when cisplatin was given before L-histidinol. Studies of L-histidinol and 5 FU had similar results. For (DBA/2 X BALB/c)F1 mice, 50 mg of L-histidinol per mouse was required for protection; for hematopoietic precursor cells, protection was dependent on the dose of L-histidinol. In contrast, both L1210 leukemia cells and colon 26 adenocarcinoma cells were more efficiently killed by combinations of L-histidinol and cisplatin. This effect depended on the doses of L-histidinol and cisplatin, a finding similar to the finding for hematopoietic precursor cells. PMID- 2913330 TI - Study of the effects of ozone in emphysematous rats. AB - The effects of short-term exposure to ozone on control and elastase-induced emphysematous rats were examined to investigate whether emphysema would change the pulmonary susceptibility to oxidant air pollution. Emphysema was induced in rats after a single intratracheal instillation of 0.2 IU elastase/g body weight. Histologically, panacinar emphysema was apparent at 2, 4, 8, and 16 wk, that is, the total duration of the experiment. The diagnosis was confirmed by morphometry: the mean linear intercepts (MLI) of elastase-treated rats were significantly increased at all observation times, whereas the internal surface areas (ISA) of the elastase-treated rats were significantly decreased. In addition, pulmonary function tests provided supportive evidence for the diagnosis of emphysema. Respiratory system compliance and functional residual capacity showed a significant increase in elastase-treated rats. No differences in inspiratory capacity or in forced vital capacity between control rats and elastase-treated rats were observed. The above data are indicative for a rat model for elastase induced emphysema. Short-term exposure to ozone of elastase-treated rats revealed panacinar emphysema, including an inflammatory response in the centroacinar region. No differences in MLI as well as in ISA between ozone-exposed rats (with or without emphysema) and their respective controls were observed. Short-term exposure to ozone induced an identical, significant increase in protein content, lactate dehydrogenase, glucose-6-phosphate dehydrogenase, and glutathione peroxidase activities in lungs of normal and emphysematous rats. Moreover, these results strongly suggest that emphysematous rats are not more susceptible to ozone than nonemphysematous rats. PMID- 2913329 TI - Cancer risk in population examined with diagnostic doses of 131I. AB - Previously, we conducted a study of 35,074 patients receiving diagnostic doses of 131I for suspected thyroid disorders between 1951 and 1969. We reported that, between 1958 and 1984, the incidence of thyroid cancers in these patients was insignificantly greater than the incidence expected in the general population. This increase was attributed to the underlying condition that prompted the examination and not to the administration of 131I. The purpose of the present study was to analyze the total cancer risk in the same cohort of patients examined with diagnostic doses of 131I. To further evaluate the underlying risk of disease in these patients, we compared the incidence of all cancers with that expected in the general population. The average radiation dose was approximately 500 mGy to the thyroid and less than 10 mGy to other organs. In the 35,074 patients, 3,746 cancers occurred following the first 5 years after examination, and the resulting standardized incidence rate (SIR) was 1.01 (95% confidence interval = 0.98-1.04). SIRs were significantly increased for endocrine tumors other than thyroid cancer (1.93) and for lymphomas (1.24), leukemias (1.34), and nervous system tumors (1.19). The risk of leukemia was similar for chronic lymphocytic leukemia (CLL) (SIR = 1.30) and non-CLL (SIR = 1.34). SIR was significantly decreased for cancers of the female genital organs (0.86). The risk for cancer of all sites and types combined was highest 5-9 years after examination (SIR = 1.07) and did not differ from unity thereafter. With greater than or equal to 10 years of follow-up, risk was not statistically associated with the dose of 131I. Overall, the data exclude cancer risk increments greater than 5% (SIR = 1.05) with 95% confidence. The significant increase in the risk of non-CLL, a prominent radiogenic malignancy, however, warrants special attention. We are continuing our study to determine the possible factors involved in the significant increase in the risk of leukemia. PMID- 2913331 TI - Phagolysosomal alterations induced by unleaded gasoline in epithelial cells of the proximal convoluted tubules of male rats: effect of dose and treatment duration. AB - Short-term oral administration of unleaded gasoline to male rats reproduces the accumulation of phagolysosomes (hyaline droplets) in epithelial cells of the renal proximal convoluted tubules (PCT) observed following long-term inhalation of wholly volatilized gasoline. Phagolysosomes are partially composed of alpha 2u globulin, a low-molecular-weight protein, unique to male rats. In this study, dose-dependent and chronologic alterations of phagolysosomes caused by gasoline were observed by transmission electron microscopy. Exposure to commercially available unleaded gasoline (0.4-2.0 ml/kg, po, once daily, 9 d) increased the number and size of phagolysosomes in epithelial cells of the PCT in male rat kidney. However, administration of 0.04 ml gasoline/kg or less was ineffective in inducing phagolysosomal accumulation. Subcellular analysis revealed that many of the phagolysosomes observed in treated rats (doses greater than 0.4 ml/kg) were angular and had cross-sectional diameters varying from 0.5 to 9 microns; in controls the majority of phagolysosomes were round and their diameter varied from 0.5 to 2.5 microns. Treatment of male rats with gasoline (2.0 ml/kg body weight, po, 1-9 d) caused a progressive increase in the number and size of phagolysosomes in PCT epithelial cells dependent on treatment duration. Alterations in phagolysosomal morphology and quantity occurred within 20 h following a single dose of gasoline, emphasizing that the process of phagolysosome accumulation is a dynamic phenomenon. Many of the enlarged phagolysosomes contained a condensed, crystalline core of greater electron density than the surrounding matrix. Furthermore, the rapid increase in abnormal, condensed contents in the phagolysosomes may indicate that a derangement of renal protein catabolism is the primary mechanism by which fuel hydrocarbons cause hyaline droplet nephropathy in male rats. PMID- 2913332 TI - Urinary 1-hydroxypyrene levels in workers handling petroleum coke. PMID- 2913333 TI - Effects of parenteral di-(2-ethylhexyl)phthalate (DEHP) on gonadal biochemistry, pathology, and reproductive performance of mice. AB - Male and female mice were treated subcutaneously (sc) with 1-100 ml/kg of di-(2 ethylhexyl) phthalate (DEHP) on d 1, 5, and 10 of the experiment and evaluated at d 21 for reproductive performance, selected biochemical parameters of the gonads, and histological alterations of the gonads. In both male and female treated mice there was a reduction in incidence of pregnancy. There were biochemical suggestions of reduced anabolic activity in the gonads (as reflected by decreased ATPase activity and of RNA, DNA, and protein content), and of increased catabolic activity in the gonads (as reflected by an increase in lysosomal enzyme activity and histological damage). Testicular, but not ovarian, weight was reduced in treated animals. Of the other parameters examined, the ovaries exhibited histological injury at lower doses of DEHP than the testes, but unlike testes, there was not a significant dose-related increase in histopathology. Biochemical changes were dose-related, for the most part, in both ovaries and testes, with the changes being more pronounced in testes. In general, reduced fertility appeared to be the most sensitive indicator for gonadotoxicity from DEHP, followed by biochemical changes and histological evidence of injury to the gonads. PMID- 2913334 TI - Delayed neurotoxic effects of tri-o-tolyl phosphate in the European ferret. AB - The development of organophosphorus-induced delayed neurotoxicity (OPIDN) was studied in the European ferret (Mustela putorius furo). A single oral or dermal dose of 250, 500, or 1000 mg tri-o-tolyl phosphate (TOTP)/kg body weight was administered to adult male ferrets. Corn oil served as the vehicle in the oral test and 95% ethanol was the vehicle in the dermal test. At 48 h posttreatment, half the animals in each group were killed by cervical dislocation for assessment of whole-brain neuropathy target esterase (NTE) activity. The remaining 5 animals per group were observed and examined neurologically on a daily basis for a subsequent 54 d. All ferrets dosed dermally with 1000 mg TOTP/kg body weight developed clinical signs characteristic of OPIDN ranging from ataxia to partial paresis. Ferrets administered 250 and 500 mg TOTP/kg body weight via the dermal route displayed variable degrees of hind limb weakness and ataxia. Of the animals dosed orally, only those in the 1000 mg TOTP/kg body weight group showed clinical signs indicative of OPIDN. These signs did not progress beyond mild ataxia. Small amounts of axonal degeneration were noted in the dorsolateral part of the lateral funiculus and in the fasciculus gracilis of spinal cords in ferrets receiving dermal doses of 1000 mg TOTP/kg body weight. Whole-brain neuropathy target esterase activity was also maximally inhibited (46%) in animals receiving 1000 mg TOTP/kg dermally. These results suggest that the ferret is a species that is susceptible to OPIDN. PMID- 2913335 TI - Effects of purified altertoxins I, II, and III in the metabolic communication V79 system. AB - Purified Alternaria alternata altertoxins I, II, and III were evaluated for comparative cytotoxicity and ability to inhibit gap junction communication in the Chinese hamster lung metabolic cooperation assay. The noncytotoxic test range for each altertoxin was determined for the metabolic communication assays: altertoxin I, 1, 2, 3, 4, 5 micrograms/ml; altertoxin II, 0.02, 0.008, 0.006, 0.004, 0.002, 0.0008 micrograms/ml; and altertoxin III, 0.2, 0.1, 0.08, 0.06, 0.04 micrograms/ml. Altertoxin II was the most cytoxic in the V79 system, followed by altertoxins III and I. The last cytotoxic of the three, altertoxin I, weakly disrupted metabolic communication at two concentrations (4 and 5 micrograms/ml). Altertoxins III and II did not significantly inhibit gap junction communication more than the weak tumor promoter 4-O-methyl ether tetradecanoylphorbol 13 acetate. PMID- 2913336 TI - Study of hepatotoxicity in isolated perfused liver versus cultures of rat hepatocytes. AB - Isolated perfused liver and cultures of rat hepatocytes were assessed for the quantitative evaluation of hepatotoxicity. Release of de novo biosynthesized plasma proteins and acid hydrolases into perfusion or culture media was taken as an indication of the integrity of hepatocytes in both systems. The activities of six acid hydrolases, alpha-L-fucosidase, alpha-D-galactosidase, beta-D galactosidase, beta-D-N-acetylgalactosaminidase, beta-D-N-acetylglucosaminidase, and cathepsin D, were assayed in collagenase-segregated hepatocytes and in monolayer cultures of rat liver cells obtained via collagenase perfusion of rat liver. In situ, liver perfusion with collagenase led to a loss of 45 +/- 5% of the total acid hydrolase activity in the mitochondrial-lysosomal pellet of the liver cells with concomitant increase of these enzymes in the cytosol. In monolayer cultures over a period of 30 h, increased activity of cathepsin D, beta D-galactosidase, and beta-D-N-acetylglucosaminidase in the mitochondrial lysosomal pellet and the cytosol fraction was evident with concurrent biosynthesis of plasma proteins. The use of radioactive tracing techniques with the isolated perfused liver revealed that the rate of catabolism of intracellular protein was approximately 5 times that of plasma protein synthesis. Both methods described here are suitable for the study of the effects of toxins on the function of hepatocytes. PMID- 2913337 TI - Pneumothorax and an azygos lobe. PMID- 2913338 TI - The diaphragm, chest wall, and pleura. PMID- 2913339 TI - Coil embolization in the treatment of pulmonary arteriovenous malformations. AB - Twenty-eight pulmonary arteriovenous malformations in six patients were treated with coil embolization. The technique of embolization and the precautions taken to avoid complications are described. All patients had good relief of their symptoms and an improvement in arterial oxygenation. The observed complications were minor and our technique has now been modified to avoid these. PMID- 2913340 TI - Ruminations and resolutions. PMID- 2913341 TI - Posterior transthoracic approach for adrenal surgery. AB - We present a modification of the posterior surgical approach for adrenalectomy wherein the pleura and diaphragm are directly incised to expose the adrenal gland. This technique has been used in 20 patients undergoing adrenalectomy for hyperplasia or a small benign adenoma. In our series chest tube drainage usually was not necessary, operative morbidity was minimal and most patients were discharged from the hospital within 1 week postoperatively. The posterior surgical approach remains an excellent method to perform adrenalectomy in selected patients. The transthoracic modification described can enhance operative exposure of a high-lying adrenal gland through this incision, particularly on the right side. PMID- 2913342 TI - The Cleveland Clinic experience with adrenal cortical carcinoma. AB - Between 1936 and 1987, 82 patients with adrenal cortical carcinoma were seen at our clinic. Of these patients 49 (72 per cent) have been seen during the last 25 years. A total of 40 patients (48.8 per cent) presented with a hormonally functional tumor and 42 (51.2 per cent) had a nonfunctional tumor. Forty patients (48.8 per cent) presented with localized disease, 12 (14.6 per cent) with regional disease and 30 (36.6 per cent) with distant metastases. Complete surgical removal of all gross tumor was achieved in 49 patients. Over-all 3 and 5 year patient survival rates in this series were 37.5 and 25.1 per cent, respectively. Survival was significantly improved (43.9 per cent at 5 years, p equals 0.0001) in patients with localized disease that was completely removed surgically; postoperative adjuvant therapy with op'-DDD was of no benefit in these patients. Survival in patients with metastatic disease was poor and was not improved by treatment with op'-DDD, cytotoxic chemotherapy or radiation therapy. PMID- 2913343 TI - Trichlormethiazide and oral phosphate therapy in patients with absorptive hypercalciuria. AB - In a short-term prospective study 36 patients with absorptive hypercalciuria were initially treated with diet alone followed by either trichlormethiazide (4 mg. per day) or oral neutral phosphate (1,500 mg. of elemental phosphorus per day) for 6 weeks. Study subjects were then crossed over to the second drug for an additional 6 weeks. In response to dietary treatment urinary calcium decreased from a pre-treatment value of 346 +/- 63 mg. per 24 hours to 308 +/- 90 mg. per 24 hours. Oral phosphate therapy caused a further decrease in urinary calcium to 218 +/- 85 mg. per 24 hours, an over-all decrease of 37 per cent. Parathyroid function did not change significantly with phosphate administration but circulating levels of 1,25-dihydroxyvitamin D decreased by 22 per cent (73 +/- 12 to 57 +/- 16 pg. per ml., p less than 0.001). Pre-treatment renal phosphate threshold did not correlate with the response to oral phosphate administration. Trichlormethiazide treatment led to a 34 per cent decrease in urinary calcium with a mean value on treatment of 228 +/- 80 mg. per 24 hours. 1,25 Dihydroxyvitamin D levels decreased by 10 per cent. Pre-treatment fasting calcium excretion, parathyroid function and 1,25-dihydroxyvitamin D levels did not correlate with the response to trichlormethiazide. We conclude that both drugs by pharmacological means improve the biochemical abnormalities in absorptive hypercalciuria and should be efficacious in its treatment. PMID- 2913344 TI - Extracorporeal shock wave lithotripsy of stones in the mid ureter. AB - We treated successfully 16 patients with stones in the mid ureter, that is overlying the pelvic bone, in the prone position with a Dornier HM3 lithotriptor. The lithotriptor was equipped with the original reflector and generator system, and all treatments were performed with only surface anesthesia of the skin and premedication with pethidine chloride and diazepam. Between 1 and 3 sessions were necessary with up to 2,000 shock waves at each session. The generator voltage was varied between 14 and 18 kv. After completion of extracorporeal shock wave lithotripsy all patients became free of stones without ureteroscopy or transureteral manipulation except for a ureteral catheter and fluid irrigation during treatment. PMID- 2913345 TI - Management of benign ureteral structures: open surgical repair or endoscopic dilation? AB - We reviewed 20 cases of ureteral strictures, 15 of which were secondary to ureteral trauma. Of the patients 6 were managed initially by open repair and 14 underwent endoscopic manipulation. All 6 open repairs were successful, compared to 9 of the 14 patients who underwent endoscopic dilation of the ureteral stricture. Of the 5 failures 3 were due to the inability to cannulate the strictured ureter with a guide wire and 2 failed to respond to balloon dilation. Of these 5 patients 4 were treated successfully by an open operation. There were no serious intraoperative or postoperative complications. The average hospitalization was less for the endoscopic group (2.1 days) compared to the open surgical group (8.3 days). Followup ranged from 6 to 48 months. PMID- 2913346 TI - The management of chronic interstitial cystitis by substitution cystoplasty. AB - A total of 19 patients with interstitial cystitis symptoms intractable to conservative management underwent supratrigonal excision of the symptomatic bladder. Reconstruction to produce a low pressure reservoir was accomplished with a segment of remodeled intestine anastomosed to the bladder remnant. Patients were selected because of a history of typical intractable severe symptoms in the presence of characteristic endoscopic features. Of the patients 12 were cured of the pain and frequency, 4 experienced improvement, and 3 failed to improve and underwent urinary diversion. Preoperative features did not predict the outcome, although poor results occurred more often in those with large preoperative bladder capacities while under anesthesia and those who had postoperative voiding problems requiring self-catheterization. PMID- 2913347 TI - A study of functional recovery for urination and defecation in patients with myelodysplasia: a modified seromuscular ileal flap fixation to the bladder. AB - From 1978 to 1985, 57 myelodysplasia patients with urinary and defecatory dysfunction underwent surgical treatment by modified seromuscular ileal flap fixation to the bladder. Followup was 1 to 88 months. Bladder capacity did not decrease, and voiding time and urine flow rate significantly improved. A urinary substitute sensation appeared in 45 of 46 patients (97.8 per cent) and urinary incontinence improved in 36 of 37 (97.3 per cent). A fecal substitute sensation appeared in 31 of 46 patients (67.4 per cent) and constipation improved in 22 (47.8 per cent). Operative complications were encountered in 5 of 57 patients (8.8 per cent), including 3 cases of prolonged paralytic ileus, 1 obstructive ileus and 1 wound herniation. Modified seromuscular ileal flap fixation to the bladder appears to be indicated for patients with the lower type of neurogenic bladder with neither a low compliance bladder nor high grade vesicoureteral reflux. PMID- 2913348 TI - Nuclear deoxyribonucleic acid ploidy in squamous cell bladder cancer. AB - Flow cytometric analysis of nuclear deoxyribonucleic acid content was performed on 76 primary squamous cell bladder carcinomas treated between January 1970 and December 1975. Patients were followed for a median of 10.1 years. Nuclei were extracted from paraffin-embedded archival material and isolated nuclei were stained with propidium iodide. Of the 76 tumors 73 were evaluable by flow cytometry providing high quality deoxyribonucleic acid histograms: 27 (37 per cent) showed a deoxyribonucleic acid diploid or normal pattern, 17 (23 per cent) exhibited a significant increase in the 4C peak (deoxyribonucleic acid tetraploid) and 29 (40 per cent) showed a distinct aneuploid peak. High grade (grades 3 and 4) and high stage (stages T2 to T4) tumors had a significantly higher incidence of abnormal (either tetraploid or aneuploid) deoxyribonucleic acid patterns than low grade (grades 1 and 2) and low stage (stages Tis/Ta/T1) tumors (p less than 0.005). The 5 and 10-year rate free of disease for patients with deoxyribonucleic acid diploid tumors was 67 per cent compared to 22 and 18 per cent, respectively, for patients with tumors showing abnormal ploidy patterns (p less than 0.0005). At 5 and 10 years after diagnosis an estimated 18 per cent of the patients with deoxyribonucleic acid diploid tumors will die of bladder cancer. In contrast, an estimated 53 per cent of the patients with tetraploid tumors and 82 per cent and 86 per cent of those with aneuploid tumors will die of squamous cell bladder carcinoma by 5 and 10 years after diagnosis (p less than 0.0001). These results demonstrate that nuclear deoxyribonucleic ploidy measured by flow cytometry is an important objective prognostic variable for patients with squamous cell carcinoma of the bladder. PMID- 2913349 TI - Behavioral training for post-prostatectomy urinary incontinence. AB - We treated 20 men with persistent post-prostatectomy incontinence by biofeedback assisted behavioral training procedures. Initially, scheduled 2-hour voiding resulted in a mean 33.1 per cent increase in urge incontinence, a mean 28.5 per cent decrease in stress incontinence and no change in continual leakage. Subsequently, biofeedback was used to teach selective control of the sphincter muscles and/or inhibition of detrusor contractions. Individualized home practice included a voiding schedule, sphincter exercises, active use of the sphincter to prevent urine loss and strategies to manage urgency. After 1 to 5 biofeedback sessions patients with urge incontinence demonstrated an average 80.7 per cent decrease in incontinence, while stress incontinence was decreased an average 78.3 per cent and patients with continual leakage were less successful, with a mean 17.0 per cent improvement. The findings indicate that biofeedback training is an effective intervention for episodic stress or urge incontinence after prostatectomy. However, its usefulness appears to be limited in patients with postoperative incontinence characterized by continual leakage. PMID- 2913350 TI - Experience with the artificial urinary sphincter model AS800 in 148 patients. AB - The latest version of the artificial urinary sphincter, AS800, was used in 148 patients with urinary incontinence of different etiologies. Followup ranged from 3 to 37 months, with an average of 20.8 months. There were 112 (76 per cent) male and 36 (24 per cent) female patients. The cuff was implanted around the bladder neck in 78 patients (53 per cent) and around the bulbar urethra in 70 (47 per cent). Socially acceptable urinary control was achieved in 90 per cent of the 139 patients with active devices in place. It was necessary to remove the sphincter in 11 patients (7.4 per cent). The reasons for removal were infection and erosion in 8 patients (5.4 per cent), infection without erosion in 2 (1.3 per cent), and erosion due to excess pressure and poor tissues in 1 (0.7 per cent). Comparison of success and failure rates associated with incontinence of different etiologies revealed that patients with incontinence after failure of a conventional antistress incontinence operation and those with incontinence after transurethral resection or radical prostactectomy had the highest success rate, and that patients with incontinence secondary to pelvic fracture or exstrophy and epispadias had the highest failure rates. The deactivation feature (the lock) of the new artificial sphincter model was beneficial for primary deactivation, urethral catheterization or cystoscopy, or for elective nocturnal decompression of the bladder neck or urethral tissues. PMID- 2913351 TI - Bulbocavernosus reflex: its validity as a diagnostic test of neurogenic impotence. AB - Measurement of the bulbocavernosus reflex is used widely to diagnose underlying neurogenic disorders in erectile dysfunction. A prolonged bulbocavernosus reflex latency (that is more than 45 msec.) or the absence of a reflex response of the bulbocavernosus muscles during electrical stimulation of the glans penis is considered a sign of neurological disease. Since only a few experimental studies have been performed in man related to the neurophysiological mechanism of erection, and since the results of these studies were contradictory the diagnostic validity of bulbocavernosus reflex measurement was reassessed. We determine whether men with abnormal bulbocavernosus reflex latencies have concomitant organic erectile dysfunction as confirmed by nocturnal plethysmographic and rigidity recordings. The bulbocavernosus reflex was recorded in 90 subjects and 19 had abnormal bulbocavernosus reflex latencies. Of these 19 subjects 8 had normal nocturnal erections, thus, confirming a diagnosis of psychogenic impotence. These results cast some doubts on the validity of bulbocavernosus reflex measurement for the diagnosis of organic erectile dysfunction due to a neurological disease. PMID- 2913352 TI - Primary erectile dysfunction. AB - We evaluated 67 patients 18 to 60 years old (mean age 28.5 years) with primary erectile dysfunction (absence of full sustained erections since early childhood or puberty) using a multidisciplinary approach. Organic causes of the erectile dysfunction were found in 57 of the 67 patients (85 per cent): 12 (18 per cent) had neurological, 35 (52 per cent) arteriogenic and 35 (52 per cent) venogenic abnormalities. Psychogenic factors were diagnosed in 11 patients (16 per cent), while in 4 (6 per cent) a classification was not possible. Concomitant psychogenic abnormalities were found in 39 of the 57 patients (68 per cent) with organic primary erectile dysfunction. Our results suggest that primary erectile dysfunction is caused mainly by organic factors. However, for successful therapy the frequent secondary psychogenic abnormalities must be considered. PMID- 2913353 TI - Vacuum constriction device for management of erectile impotence. AB - A mechanical device for treatment of impotence based on the concept of entrapment of blood in the penis following vacuum-assisted tumescence is described and more than 15,000 units have been marketed. A total of 1,517 users who acquired the device between 1974 and 1987 completed a questionnaire concerning the system. Of these patients 92 per cent either achieved an erection or an erection-like state that was satisfactory for intercourse and 77 per cent had intercourse at least every 2 weeks. No serious ill effect from use of the device has been reported a and it is particularly effective in the management of partial impotence. In selected patients the device is an alternative to either surgical placement of a penile prosthesis, intracavernous injection of vasoactive drugs or sexual abstinence. PMID- 2913354 TI - Intracavernous injection of prostaglandin E1 for the treatment of erectile impotence. AB - We administered intracavernous injections of 20 micrograms. prostaglandin E1 to 135 patients with impotence, and evaluated the effects and side effects. Among 135 patients who underwent intracavernous injection of prostaglandin E1 complete erection was observed in 83 (62 per cent), while incomplete erection was noted in 33 (24 per cent). In both groups the erection was sufficient for sexual intercourse. Tumescence without rigidity was noted in 12 patients and no response was obtained in 7. Poor response was seen frequently in patients with disorders of the vascular system and/or damage to the cavernous body of the penis. Priapism after the injection was not observed. Moreover, we never observed any other severe side effects. Intracavernous injection of prostaglandin E1 could be applicable to the therapy of impotence, especially that due to neurogenic disturbance. Since prostaglandin E1 acts quickly and loses its validity rapidly it is considered to be a more suitable agent than other vasoactive drugs. PMID- 2913355 TI - Case-control study of men with suspected chronic idiopathic prostatitis. AB - We studied prospectively 50 asymptomatic men (24 men from infertile couples and 26 normal volunteers) with no history of genitourinary infection and 34 men referred for symptoms of chronic prostatitis. Both groups were evaluated by urethral and prostatic secretion cultures for Chlamydia trachomatis, 4-glass prostatic localization cultures for facultative aerobic bacteria (Ureaplasma urealyticum, Mycoplasma hominis and selected fungi) and counts of prostatic fluid leukocytes. The men with symptoms of prostatitis had more than 1,000 leukocytes per mm. in prostatic secretions more often than did controls (11 of 27 versus 0 of 44, p less than 0.001). The concentration of Ureaplasma urealyticum in prostatic secretions was 1 log higher in prostatic fluid localization cultures than in first voided urine in 0 of 30 patients versus 13 of 50 controls (p equals 0.0014). Chlamydia trachomatis was not isolated from any patient or control. No other significant differences were found between patients and controls. We did not identify an infectious cause of chronic nonbacterial prostatitis. PMID- 2913356 TI - Morphometric measurement of tumor volume and per cent of gland involvement as predictors of pathological stage in clinical stage B prostate cancer. AB - Although tumor volume is an important factor in predicting prognosis in carcinoma of the prostate, direct and accurate estimation of tumor volume is not practical clinically at present because the tumor may not always be palpable (stage A) and when palpable it is difficult to estimate volume in 3 dimensions. For this reason the clinical staging of prostate cancer currently is based on estimations of the per cent of gland involved with tumor: in stage A by per cent of tissue involved with cancer and in stage B by digital palpation (less than 1 lobe, 1 lobe and 2 lobes). In stage A prostate cancer the per cent of the specimen involved with tumor and the volume of tumor have been shown to correlate with tumor progression. Our study was designed to determine if either or both of these morphometric factors would be good predictors of pathological stage in stage B prostate cancer. We analyzed 56 step-sectioned radical prostatectomy specimens: 28 without capsular penetration, 15 with capsular penetration only and 13 with seminal vesicle involvement. The per cent of gland involved with tumor (correlation coefficient 0.67, p less than 0.001) and tumor volume (correlation coefficient 0.55, p less than 0.001) correlated well with pathological stage. Stepwise linear regression showed that the combination of the per cent of gland involved with tumor and the total Gleason grade was statistically the best predictor of pathological stage. PMID- 2913357 TI - Transitional cell carcinoma of the prostate in cystoprostatectomy specimens removed for bladder cancer. AB - Specimens from 84 radical cystectomies for bladder carcinoma performed between January 1984 and July 1986 were reviewed to characterize the involvement of the prostate with transitional cell carcinoma. Whole-mount sectioning of the prostate was performed at 4 mm. intervals and processed in the same manner as radical prostatectomy specimens. A total of 36 patients (43 per cent) had transitional cell carcinoma of the prostate: 94 per cent of these had prostatic urethra involvement and 6 per cent had a normal prostatic urethra but transitional cell carcinoma was present in the periurethral structures. In situ prostatic duct or acini, ejaculatory duct and seminal vesicle involvement occurred, respectively, in 67, 8 and 17 per cent of the patients with prostatic involvement. Of the patients with prostatic involvement 39 per cent had stromal invasion (22 per cent focal and 17 per cent diffuse invasion). The incidence of carcinoma in situ of the bladder neck or trigone (59 per cent), previous intravesical chemotherapy (59 per cent) and ureteral carcinoma (79 per cent) was significantly increased in patients with prostatic involvement. In patients with carcinoma in situ of the trigone or bladder neck, or in whom previous intravesical chemotherapy treatments have failed prostatic involvement should be suspected so that this disease can be detected before stromal invasion occurs. PMID- 2913358 TI - Trigonal sensitivity testing in women. AB - Tests of the integrity of bladder sensation are a poorly understood and often neglected part of urodynamic investigations. The electrical techniques that have been described to test sensation involve the use of costly and complex equipment; electrical current also is not the natural stimulator of bladder nerves. Trigonal sensitivity testing held promise as a simple, effective and inexpensive test of bladder sensation. We evaluated a modified version of this technique in 89 women: 78 had urodynamically proved lower urinary tract dysfunction and 11 were control patients. The technique proved to be of no value in distinguishing among various urodynamic diagnoses. In particular, patients with detrusor instability or bladder hypersensitivity showed no characteristic patterns on trigonal sensitivity testing. Sensitivity values correlated neither with the first sensation to void nor the cystometric bladder capacity during urodynamic testing. It does not appear to contribute any clinically useful information in the evaluation of lower urinary tract dysfunction in women. PMID- 2913359 TI - The GAP (glans approximation procedure) for glanular/coronal hypospadias. AB - A modified glanuloplasty is described for the selective repair of glanular and coronal hypospadias with a wide, deep glanular groove and noncompliant urethral meatus. No urinary diversion is required, and cosmetic and functional results are excellent. A total of 24 children underwent the GAP (glans approximation procedure) during 20 months. Followup ranged from 3 months to 1.5 years with no evidence of meatal or urethral stenosis. One distal glanular fistula developed that required division of a 2 mm. skin bridge that separated the fistulous opening from the neomeatus. PMID- 2913360 TI - Abacterial prostatitis: more about what it isn't but what is it? PMID- 2913361 TI - A case of vesical varices as a complication of portal hypertension and manifested gross hematuria. AB - We report a unique case of vesical varices in a patient who presented with an episode of serious gross hematuria. He also had cirrhosis of the liver and portal hypertension, and had undergone transection of the esophagus 10 years ago. A hemangiomatous mass was discovered on cystoscopic examination, and sonographic examination, computerized tomography and abdominal angiography revealed vesical varices. The genesis of vesical varices and possible treatment in this case are discussed. PMID- 2913362 TI - Artificial urinary sphincter implantation after pubectomy for bone tumor. AB - We report 2 cases of unilateral and bilateral excision of pubic bone tumors (chondrosarcoma and giant cell tumor). Postoperative stress incontinence was corrected by implantation of an artificial sphincter (AMS800) following which both patients were continent. The etiology of the incontinence was lack of bladder and urethral support, which was not correctable by bladder neck suspension procedures. PMID- 2913363 TI - Vas deferens calculus. AB - We describe a patient with a radiopaque calculus in the vas deferens that was inappropriately diagnosed as a ureteral calculus. PMID- 2913364 TI - Isolated necrotizing granulomatous vasculitis of the spermatic cords. AB - Isolated necrotizing granulomatous vasculitis of the spermatic cord has not been described during the last 20 years. We report clinical, laboratory and histopathological features of an instance of contralaterally recurrent lesions of this type in a young photographic laboratory technician. Although to date the disease is considered to be isolated, it may well be a systemic one without yet obvious signs. PMID- 2913365 TI - Congenital pelvic arteriovenous malformation with massive prostatic hemorrhage: a case report. AB - Congenital arteriovenous malformations in the true pelvis are extremely rare: only 7 cases have been described in male patients. We report on a patient who presented with massive hemorrhage after transrectal prostatic biopsy and transurethral resection of the prostate. Diagnosis was established by means of magnetic resonance imaging and confirmed by arteriography. Our attempt at management by embolization and subsequent surgical ligation is described. A literature review and discussion of arteriovenous anomalies are presented. PMID- 2913366 TI - The Whitaker test: experimental analysis in a canine model of partial ureteric obstruction. AB - The Whitaker test has been described as a means of reaching a diagnosis in equivocal upper urinary tract obstruction, but there has been conflicting evidence regarding the validity of this test. The present study assesses the reliability of the test in an experimental model which creates an accurate and predetermined degree of partial obstruction of the ureter. The Whitaker test was performed using the standard perfusion rate of 10 ml./min. in male adult dogs using a long-term indwelling renal intrapelvic cannula before and after application of ureteric obstruction, and after one month. Control animals underwent a sham procedure. Results of in vivo and in vitro perfusion studies were compared. Perfusion studies at multiple flow rates were also performed. The Whitaker test reliably detected the presence of ureteric obstruction and the degree of partial obstruction could be determined. Multiple flow rate studies did not significantly improve test results. Provoked pressures in the highest grade of obstruction were less than expected and this may be due to pyelovenous reflux. PMID- 2913367 TI - Erectile response to acute and chronic occlusion of the internal pudendal and penile arteries. AB - We designed two animal experiments to elucidate the effect of obstruction of the internal pudendal artery on erectile function. In five dogs the internal pudendal or penile artery was acutely clamped unilaterally or bilaterally with a non crushing vascular clamp. In eight dogs, the internal pudendal or penile artery was ligated, unilaterally or bilaterally, and occlusion was maintained for two months. In both models, electrodes were implanted around the cavernous nerves for electroerection. In unilateral occlusion, blood flow in the contralateral internal pudendal artery was recorded via an ultrasonic probe. In both unilateral and bilateral occlusion, intracavernous pressure in both corpora cavernosa was recorded through a 21-gauge butterfly needle connected to a Statham transducer. In the chronic model, selective pudendal angiography was done after the erection study was completed; the dogs were then sacrificed and the penile tissue was examined histologically under light microscopy. Unilateral acute clamping of the internal pudendal or penile artery caused a compensatory increase in arterial flow in the contralateral pudendal artery with only moderate impairment of intracavernous pressure on the ipsilateral side, but bilateral occlusion resulted in a marked reduction in the intracavernous pressure response to neurostimulation. In contrast, chronic obstruction of penile vessels had a minimal effect on erectile function due to the development of a rich network of collaterals around the penis. Histological evaluation revealed mild local changes in the cavernous tissue with characteristic compensatory enlargement of branches of the cavernous artery on the control side in cases of unilateral occlusion. PMID- 2913368 TI - The effect of raveron on the detrusor muscle. AB - Raveron (a European pharmaceutical consisting of swine prostate extract and m creosal) was studied in vivo in female mongrel dogs and in vitro bladder studies were conducted on male New Zealand rabbits. Intravenous administration of raveron reduced both the passive and active pressure in dog detrusor in vivo. It did not act in a dose dependent fashion. Chronic treatment with raveron for three to four months caused changes in in rabbits with vesical neck obstruction. An increase in contractility along with a reduced rate of increase in passive force (measurement of bladder stiffness) was observed in relation to obstructed rabbits without treatment. Parallel morphological changes were also observed in this group, consisting of increased muscular hypertrophy, decreased bladder wall thickness and reduced collagen content (readings taken from Masson-Trichrome sections). No influence was observed with bladder specimens from rabbits with six to eight week vesical obstruction or normals that received treatment. In vitro dose response studies showed that a 3.3% dose of raveron significantly reduced passive force in two groups (treated normals and treated rabbits with six to eight week vesical obstruction). Pharmacology studies with potassium chloride and acetylcholine suggest that raveron acts as a calcium antagonist by blocking the influx of extracellular calcium. PMID- 2913369 TI - A histochemical and immunohistochemical study of the autonomic innervation of the lower urinary tract of the female pig. Is the pig a good model for the human bladder and urethra? AB - The detrusor muscle, bladder neck, proximal, middle and distal regions of the urethra of the female pig were studied by histochemical and immunohistochemical methods to localize catecholamine-containing, acetylcholinesterase-positive and peptide-containing nerves. The peptides examined included: vasoactive intestinal polypeptide, substance P, somatostatin, [Met]enkephalin, bombesin and gastrin. The greatest density of nerves was found in the smooth muscle of the distal urethra, followed by the bladder neck, middle urethra, and proximal urethra, with the least in the detrusor muscle. The greatest number of nerve fibres stained for acetylcholinesterase, followed by vasoactive intestinal polypeptide- and catecholamine-containing fibres. Substance P-immunoreactive nerve fibres were confined to the bladder neck and distal urethral regions. [Met]enkephalin-and gastrin-immunoreactive nerves were most dense in the distal urethra but absent in detrusor muscle, while somatostatin-immunoreactive nerve fibres were sparsely distributed throughout the lower urinary tract. No nerve fibres showing immunoreactivity to bombesin were found. Catecholamine-containing, acetylcholinesterase-positive, vasoactive intestinal polypeptide-, substance P-, [Met]enkephalin- and gastrin-immunoreactive nerves were also found on the adventitial-medial border of blood vessels in the pig urinary tract. In the intrinsic external urethral sphincter, located in the distal urethra, vasoactive intestinal polypeptide- and gastrin-immunoreactive nerve fibres were found bordering a small number of individual striated muscle fibres, while catecholamine-containing nerves were found predominantly in the connective tissue surrounding the striated muscle fibres. Dense populations of acetylcholinesterase positive nerve fibres were found associated with the striated muscle fibres, with end plates on some of them. Intramural ganglia, composed of two to 30 neurones, were found in the bladder neck and middle and distal regions of the urethra. In the smooth muscle, and in the vicinity of the striated muscle regions of the intrinsic external urethral sphincter, there were small ganglia, containing two to three neurones, which were vasoactive intestinal polypeptide-, [Met]enkephalin and somatostatin-immunoreactive. The results are compared to the autonomic innervation of the human bladder and urethra as previously described and it is concluded that the lower urinary tract of the pig is a good model for some features of the lower urinary tract of man, but a poor model for others. PMID- 2913370 TI - Effect of oxalate on function of kidney mitochondria. AB - The effects of oxalate on kidney mitochondria were evaluated in vitro to test whether oxalate exposure leads to derangement(s) in mitochondrial function that could in turn promote the formation of kidney stones. Our previous studies demonstrated that oxalate is transported across the mitochondrial membrane via the dicarboxylate carrier. The present studies indicated that oxalate competitively inhibits the uptake and oxidation of exogenous malate and succinate in isolated mitochondria but has no effect on mitochondrial respiration in the presence of a mixture of glutamate plus malate or glutamate plus pyruvate. Oxalate attenuates the increase in mitochondrial respiration produced by the uncoupler CCCP or by the Ca2+ ionophore A23187, and the latter effect is more pronounced in kidney than in liver mitochondria. The apparent Ki of oxalate for the response to Ca2+ ionophore is 1.9 +/- 0.3 mM in kidney and 6.1 +/- 0.2 mM in liver mitochondria. Similarly, the ability of oxalate to attenuate calcium induced swelling of mitochondria is more dramatic in kidney than in liver mitochondria (apparent KiS of 1.7 +/- 0.1 and 18.2 +/- 0.7 mM, respectively). Oxalate has no effect on the rate of calcium uptake by energized mitochondria or on the rate of ruthenium red-insensitive calcium efflux from mitochondria in either tissue. The above findings indicate that oxalate interacts with the inner mitochondrial membrane or with processes controlling membrane integrity to a greater extent in kidney than liver mitochondria. The effects of oxalate on membrane permeability or integrity may be more important than its effects on mitochondrial energy production or calcium sequestration in the pathogenesis of calcium oxalate microlith formation in the kidney. PMID- 2913371 TI - Ureteral replacement using ileum in compromised renal function. AB - Ureteral replacement by ileum is an accepted technique in a highly selective patient population. Two major contraindications in using an ileal ureter are compromised renal function (serum creatinine greater than 2) and a functionally abnormal bladder. We used ileum to bridge a ureteral defect in animals with half of a solitary kidney and low grade azotemia to see if the antirefluxing mechanism of the lower ureter prevented further deterioration in renal function. Twelve female mongrel dogs underwent a right nephrectomy, followed by a left partial nephrectomy six weeks later. Group I (six dogs) had a six cm. segment of ileum interposed between the upper and lower ureteral segments (nonrefluxing). Group II (five dogs) had a ten cm. segment of ileum placed from the upper third of the ureter to the bladder (refluxing). Cystograms, intravenous pyelograms, serum electrolytes, BUN and creatinine were obtained preoperatively, six weeks after the right nephrectomy, one month after left partial nephrectomy and six months after ileal replacement prior to sacrifice. The BUN and creatinine deteriorated in Group II compared to Group I, p = .02 and p = 0.4 respectively (Mann-Whitney test). The BUN and creatinine also deteriorated between one month after left partial nephrectomy and six months after ileal replacement within Group II, p = .07 and p = .14, respectively (Wilcoxon matched-pairs test) but not in Group I. These data suggest that the antirefluxing mechanism of the lower ureter might prevent further deterioration in renal function. We feel that ileum can be used with caution, as an interposition in compromised renal function. PMID- 2913372 TI - Detailed anatomy of penile neurovascular structures: surgical significance. AB - In 10 formalin-preserved adult male cadavers, dissection of the penile veins, arteries and nerves revealed information of clinical importance. The main venous drainage of the corpora cavernosa is via the cavernous veins, with additional drainage through the circumflex, deep dorsal, and crural veins. The arterial supply of the cavernous bodies varied remarkably, and the incidence of an accessory internal pudendal artery was high. The cavernous nerves, previously believed to be microscopic structures, were in fact identifiable grossly, and we were able to follow them from the region of the hilum of the penis to the prostate. The nature of these nerves was then confirmed by serial histologic sectioning. This detailed knowledge of the venous drainage and arterial and nervous supply of the penis, as well as of the relationships among the cavernous structures in the hilum of the penis, can elucidate the cause of erectile dysfunction and provide a valuable guide for surgical correction of vasculogenic and neurogenic impotence. PMID- 2913373 TI - Distrust, rage may be 'toxic core' that puts 'type A' person at risk. PMID- 2913374 TI - New studies fuel controversy over universal cholesterol screening during childhood. PMID- 2913375 TI - Useful advice to patient whose spouse has died: 'establish a routine, mingle with other people'. PMID- 2913376 TI - Intensifying the war against drunken driving by discouraging alcohol consumption in general. PMID- 2913377 TI - Leads from the MMWR. Years of potential life lost before age 65--United States, 1987. PMID- 2913378 TI - Leads from the MMWR. Measles prevention: supplementary statement. PMID- 2913379 TI - Sleep deprivation and performance of residents. PMID- 2913380 TI - Alcoholism as willful misconduct. PMID- 2913381 TI - Cessation of zidovudine therapy may lead to increased replication of HIV-1. PMID- 2913382 TI - Metronidazole and cancer. PMID- 2913383 TI - Nine-ball neck. PMID- 2913384 TI - Passive smoking on commercial airline flights. AB - In-flight exposure to nicotine, urinary cotinine levels, and symptom self-reports were assessed in a study of nine subjects (five passengers and four attendants) on four routine commercial flights each of approximately four hours' duration. Urine samples were collected for 72 hours following each flight. Exposures to nicotine measured during the flights using personal exposure monitors were found to be variable, with some nonsmoking areas attaining levels comparable to those in smoking sections. Attendants assigned to work in nonsmoking areas were not protected from smoke exposure. The type of aircraft ventilation was important in determining the levels of in-flight nicotine exposure. The environmental tobacco smoke levels that occurred produced measurable levels of cotinine (a major metabolite of nicotine) in the urine of passengers and attendants. Passengers who experienced the greatest smoke exposure had the highest levels of urinary cotinine. Changes in eye and nose symptoms between the beginning and end of the flights were significantly related both to nicotine exposure during the flight and to the subsequent urinary excretion of cotinine. In addition, subjects' perceptions of annoyance and smokiness in the airplane cabin were also related to in-flight nicotine exposure and urinary excretion measures. PMID- 2913385 TI - The limited reliability of physical signs for estimating hemodynamics in chronic heart failure. AB - The cardiovascular physical examination is used commonly as a basis for diagnosis and therapy in chronic heart failure, although the relationship between physical signs, increased ventricular filling pressure, and decreased cardiac output has not been established for this population. We prospectively compared physical signs with hemodynamic measurements in 50 patients with known chronic heart failure (ejection fraction, .18 +/- .06). Rales, edema, and elevated mean jugular venous pressure were absent in 18 of 43 patients with pulmonary capillary wedge pressures greater than or equal to 22 mm Hg, for which the combination of these signs had 58% sensitivity and 100% specificity. Proportional pulse pressure correlated well with cardiac index (r = .82), and when less than 25% pulse pressure had 91% sensitivity and 83% specificity for a cardiac index less than 2.2 L/min/m2. In chronic heart failure, reliance on physical signs for elevated ventricular filling pressure might result in inadequate therapy. Conversely, the adequacy of cardiac output is assessed reliably by pulse pressure. Our results facilitate decisions regarding treatment in chronic heart failure. PMID- 2913386 TI - The ravelled sleeve of care. Managing the stresses of residency training. PMID- 2913387 TI - Adrenal insufficiency after operative removal of apparently nonfunctioning adrenal adenomas. AB - We describe a woman who developed adrenal insufficiency after removal of an apparently nonfunctional adrenal adenoma. She displayed no stigmata of Cushing's syndrome and had normal plasma and urinary cortisol levels. A second patient without clinical findings of Cushing's syndrome also had normal basal steroid levels. This patient displayed partial suppressibility with dexamethasone, had low-normal levels of serum corticotropin, and excreted a low concentration of urinary 17-ketosteroids. She also developed mild adrenal insufficiency after the operation. We believe the adrenal adenomas in these patients secreted enough cortisol to suppress the contralateral adrenal gland but not enough hormone to elevate basal steroid levels. Therefore, we suggest that all patients with adrenal masses be studied with the overnight dexamethasone suppression test rather than basal steroid hormone measurements to detect low levels of autonomous cortisol secretion. In addition, patients with adrenal masses that are not removed surgically should have serial adrenal function tests performed. PMID- 2913388 TI - Comparing tobacco cigarette dependence with other drug dependencies. Greater or equal 'difficulty quitting' and 'urges to use,' but less 'pleasure' from cigarettes. AB - About 1000 persons seeking treatment for alcohol or drug dependence were asked, relative to cigarettes, about the difficulty of quitting the use of the substance for which they were seeking treatment, the strength of their strongest urges to use, and the pleasure they derived from use. Fifty-seven percent said that cigarettes would be harder to quit using than their problem substance. These ratings were related to the level of cigarette dependence and the perceived difficulty of quitting the use of the problem substance. The alcohol-dependent persons were about four times more likely than the drug-dependent persons to say that their strongest urges for cigarettes were at least as great as their strongest urges for their problem substance. Cigarettes were generally rated as less pleasurable than alcohol or other drugs. Thus, experiential experts on dependence judge cigarette dependence as at least as "addictive" as other drug use, but not as pleasurable, indicating important similarities and differences between cigarette dependence and other forms of dependence on psychoactive substances. PMID- 2913389 TI - Options to control the rising health care costs of older Americans. PMID- 2913390 TI - No turning back: a blueprint for residency reform. PMID- 2913391 TI - A piece of my mind. An elegy. PMID- 2913392 TI - Abnormal methylation of estrogen receptor gene and reduced estrogen receptor RNA levels in human endometrial carcinomas. AB - Demethylation of specific sites or restricted genomic regions has been reported to correlate with gene activation and also with carcinogenesis. As abnormal expression of Estrogen Receptor (ER) could be involved in the genesis or progression of tumors in estrogen target tissues, the methylation of ER gene has been compared in 8 endometrial carcinomas and 29 normal endometria. In order to look for a correlation between methylation and expression, levels of ER RNA were also measured. While the 5' region of ER gene was found to be demethylated in both normal and carcinomatous tissues, there was demethylation of some specific sites in the internal part of the gene only in the carcinomas examined. In addition, in the carcinomatous tissues the levels of ER RNA were low, indicating that an increase of ER gene hypomethylation does not raise, and even may reduce, the ER expression in endometrium. The abnormal undermethylation observed in ER gene appears to be unrelated to general DNA hypomethylation which is frequently present in neoplastic tissues; nor has it been found in ER DNA isolated from breast carcinomas. These data strongly support the hypothesis that such a methylation is specifically related to endometrial transformation and therefore it can be considered an additional marker of this disease. PMID- 2913393 TI - A single-site allosteric model of intracellular androgen-receptor interaction. AB - We present a single-site, two-state model for analyzing the effect of time and ligand concentration on the extent and character of 5 alpha-dihydrotestosterone, methyltrienolone or mibolerone binding to the specific androgen receptor within cultured human genital skin fibroblasts. The model has three basic attributes: formation of the initial low-affinity androgen-receptor complex, and its transformation to a higher affinity state are irreversible, first-order processes; and receptors released from complexes in each state not only differ from each other and from their pre-liganded progenitor, but can also reassociate with androgen to yield complexes in their respective parental states. The rate constants of dissociation and apparent equilibrium binding constants of the two affinity states were determined for each of the three androgens within normal cells and those of a transformation-defective mutant. When these values are combined with estimates of the rate constants at which the complexes are formed and transformed, the model accurately simulates time-dependent changes in the slopes and character of experimental Scatchard plots. It can also generate Scatchard plots that are concave, convex or sigmoidal simply by making sequential changes in its formation or transformation constants. Thus, our model can explain complex ligand-receptor binding kinetics that have heretofore been interpreted according to alternate models of transformation and binding-site multiplicity with or without properties of cooperativity, and it supports the notion that receptor recycling involves intermediate receptor states. PMID- 2913394 TI - Transcortin biosynthesis and intracellular distribution of rat liver polyribosomes synthesizing transcortin. AB - Transcortin biosynthesis in rat has been examined using liver slices technique. The incorporation of 14C-labeled amino acids into the anti-transcortin precipitable material of liver slices has been measured and compared with that of serum transcortin. It was shown that liver synthesized transcortin with an apparent mol. wt of 66 kDa on SDS-electrophoresis which co-migrated with authentic rat serum transcortin. In order to determine an intracellular distribution of transcortin synthesizing polyribosomes, the binding character of [125J]anti-transcortin-IgG to free and membrane-bound rat liver polyribosomes has been studied. It was shown that after incubation of [125J]anti-transcortin-IgG with liver membrane-bound polyribosomes, the radioactivity was associated with the discrete polyribosome fraction in heavy polyribosome region. In similar experiments the radioactivity of [125J]anti-transcortin-IgG bound to the free polyribosomes was distributed throughout the polyribosome region. The results of our experiments obviously demonstrated that serum transcortin was synthesized exclusively on membrane-bound polyribosomes of rat liver; free polyribosomes were devoid of detectable antigenic material able to bind antibodies to transcortin. PMID- 2913395 TI - Estrogen effects on modifications of chromatin proteins in the rat uterus. AB - ADP-ribosylation and phosphorylation of chromatin proteins was studied in rat uterine nuclei isolated after estrogen treatment and then incubated with [adenylate-32P]NAD or [gamma-32P]ATP. Histone acetylation was studied in uteri from immature rats treated with estradiol by incubating the whole uterus in a medium containing [14C]acetic acid. Chromatin proteins were isolated from uterine nuclei and separated by electrophoresis on SDS polyacrylamide gels followed by autoradiography or fluorography. Chromatin proteins H1, H2B, H3, HMG 14 and HMG 17 were almost exclusively ADP-ribosylated. Uterine histones H1, H3, H4, HMG 14 and HMG 17 were phosphorylated. There was a general increase in [32P]ADP-ribose uptake in chromatin proteins after estrogen stimulation, whereas [32P]phosphate incorporation into chromatin proteins showed a biphasic pattern. The [14C]acetate activity associated with all histone proteins increased gradually after estrogen treatment. PMID- 2913396 TI - Pharmacokinetics of the antiprogesterone RU 486 in women during multiple dose administration. AB - Serum levels of RU 486 were measured by high performance liquid chromatography (HPLC) following oral intake of 12.5, 25, 50 and 100 mg twice daily (b.i.d.) for 4 days, 50 mg b.i.d. for 7 days, as well as a single dose of 200 mg of RU 486. The pharmacokinetics of RU 486 were not linear: when the daily dose of RU 486 was 100 mg or more, the serum levels were similar. The pharmacokinetic behaviour of RU 486 during the treatment period was similar between the study subjects, whereas the elimination phase pharmacokinetics showed wide individual variation. Also the mean elimination phase half-lifes (t 12) of RU 486 varied from 25.5 to 47.8 h in the groups of different regimen, yet the variation between different groups was not statistically significant. The areas under the concentration curves (AUC) were calculated. In the multiple dose study (mds) the AUC0----12h:s decreased when the administered dose of RU 486 was increased. The AUC0----12h seen after administration of 100 mg b.i.d. x 4d. (mean +/- SEM = 0.43 +/- 0.04 mumol/l x h/mg) was significantly (P less than 0.05) lower than the AUC0----12h:s obtained with administration of 12.5 mg b.i.d. x 4d. (1.49 +/- 0.37 mumol/l x h/mg), 25 mg b.i.d. x 4d. (1.09 +/- 0.15 mumol/l x h/mg), and 50 mg b.i.d. x 7d. (0.72 +/- 0.11 mumol/l x h/mg). The AUC0----infinity obtained by administration of a single dose of 200 mg of RU 486 (sds) was 0.67 +/- 0.21 mumol/l x h/mg. It is concluded that if multiple dose administration of RU 486 is preferred, daily administration of relatively small doses of RU 486 over several days seem to be advantageous. PMID- 2913397 TI - Isolation and characterization of a 50 kDa testosterone-binding protein from Pseudomonas testosteroni. AB - A testosterone-binding protein (Mr = 50,500) has been isolated from the Gram negative bacterium Pseudomonas testosteroni. The protein was partially purified by a combination of ion exchange chromatography and chromatofocusing. Final purification was achieved by electroelution of the 50 kDa protein from SDS polyacrylamide gels. Following renaturation from a diluted solution of guanidine HCl, specific binding of [3H]testosterone to the purified protein was observed. The native protein has a pI of 6.8. It appears to contain 428 amino acids, 39% of which are hydrophobic. There is only one cysteine residue. Both chymotrypsin and V8 protease were used to produce peptide maps of the protein for use in future identification. The first 10 amino acids situated at the N-terminal of the protein were Ser-Pro-Phe-Asp-Leu-Arg-Pro-Leu-Ser-Gly. Testosterone binding to the protein was saturable at approximately 3.8 nmol/mg protein; the binding constant was approximately 25 nM. Unlabelled testosterone, androstenedione, 5 alpha dihydrotestosterone and 5 beta-dihydrotestosterone were able to compete for [3H]testosterone bound to the protein; 17 beta-estradiol also competed for [3H]testosterone but to a lesser degree. Neither progesterone nor desoxycorticosterone competed for the testosterone-binding site. Binding of testosterone to the protein was stable at pH's ranging from 5.5 to 9.0 and at various temperatures ranging from 4 to 30 degrees C. The protein was unable to metabolize testosterone in either the presence or absence of the cofactor NAD. PMID- 2913398 TI - Tissue specific effects of progesterone on progesterone and estrogen receptors in the female urogenital tract. AB - The effect of progesterone administration on progesterone and estrogen receptors in the uterus, vagina and urethra of rabbits was studied. After 24 h of progesterone treatment the concentration of cytosolic progesterone receptors decreased to about 25% of the control value in the uterus, whereas no significant change in receptor concentration was observed in the vagina or the urethra. The concentration of the nuclear progesterone receptor did not change in any of the three tissues studied. The apparent dissociation constant (Kd) of nuclear progesterone receptor increased after progesterone treatment in all three tissues. Although the Kd of the cytosolic progesterone receptor also increased in all tissues, the difference was significant for only the vagina and urethra. The concentration of cytosolic estrogen receptors in the uterus decreased significantly (P less than 0.001) after progesterone treatment whereas the Kd value increased slightly (P less than 0.05). In vagina or the urethra, there was no change in either estrogen receptor concentration or Kd values after progesterone treatment. These data clearly showed that the reduction by progesterone of progesterone and estrogen receptor concentrations occurs only in the uterus and not in the vagina or the urethra. PMID- 2913399 TI - Estradiol receptor-nuclear interactions in aging mouse uteri: the role of DNA and nuclear matrix. AB - We have studied the interactions of estradiol receptor (ER) with nuclear DNA or matrix (NM) in the uteri from young, middle-aged and old mice. Recombination studies using heat-activated ER and nuclear subfractions from various age groups suggested a 30% reduction for DNA binding (P less than 0.05) but not for NM with aging. Cross-incubation studies of heat-activated ER with nuclear subfractions from mice of all three age subgroups showed that this reduced DNA binding ability followed the onset of anestrous and did not result from proteolytic degradation of ER complexes. PMID- 2913400 TI - Size heterogeneity of affinity labeled estrogen receptors in the MtTF4 tumor whose growth is inhibited by estradiol, in pituitary gland and uterus. AB - Estrogen receptors (ER) of the MtTF4 tumor whose growth is inhibited by estradiol (E2) were analyzed and compared to those of tissues whose growth is stimulated by E2 (uterus and pituitary gland). Cytosol prepared in buffer containing protease inhibitors was incubated with [3H]tamoxifen aziridine ([3H]TAZ) in the presence or absence of non-radioactive competitor. The labeled proteins were precipitated, separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in denaturing conditions and detected by fluorography. Two classes of ER were identified. The first class is of high molecular weight (Mr = 65,000-64,000). In normal tissues, it is indeed frequently made up of two subtypes as revealed by the presence of a doublet on autoradiograms. In the MtTF4 tumor these subtypes were only rarely suspected and never they were as marked and distinct as in normal tissues. The second class, of low molecular weight (Mr ! 54,000-52,000), is also frequently made up of two subtypes in the uterus and the proportion of this class is higher in the uterus of mature than of immature rats. The MtTF4 tumor contains this class of ER but, due to the presence of non-specifically labeled proteins in this region, its relative amount cannot be estimated and the doublet was exceptionally revealed. In the pituitary gland, this small receptor has not been found. CONCLUSIONS: (i) On the basis of molecular weight analyses, estrogen receptors are heterogeneous, (ii) the ER pattern depends on the type of tissue and the sexual maturity of rats but all the tissues examined contained at least one type of the "classic" high molecular weight receptor, and (iii) no evident correlation was found between the ER pattern and the positive or negative response to estradiol. PMID- 2913401 TI - Reactivation of the androgen receptor from murine preputial gland by thioredoxin or GSH. AB - The androgen receptor from murine preputial gland was inactivated by density gradient centrifugation, affinity chromatography and isoelectric focusing. The hormone binding of the receptor could be partially restored (roughly 40%) by the thioredoxin-thioredoxinreductase system, by thioredoxin plus dithiothreitol or by glutathione. Dithiothreitol, by itself, was unable to reactivate the androgen receptor. These findings show that the receptor inactivation is, at least partially, due to thiol group oxidation and removal of SH-reducing and/or stabilizing substances from the receptor during purification. PMID- 2913402 TI - Comparative affinity of the major genetic variants of human group-specific component (vitamin D-binding protein) for 25-(OH) vitamin D. AB - Binding studies with [3H] 25-(OH) D3 were performed under a variety of conditions using Gc (Vitamin D-binding protein) purified from individuals displaying different phenotypes. No significant differences in affinity of binding were found between Gc1f, Gc1s and Gc2 allelle products in either homozygous or heterozygous individuals, nor between Gc1 anodal and Gc1 cathodal isotypes. Affinity was not significantly affected by different reaction temperatures (4, 22 or 37 degrees C), the presence or absence of Ca2+ ions, and binary and ternary interactions with G-actin and G-actin-DNase complexes respectively. However, reduction of pH caused a progressive decrease in binding with virtual abolition at pH less than or equal to 5.0. The latter might promote dissociation of D3 metabolites from Gc carrier protein in acidic compartments of cells. PMID- 2913403 TI - Androgen metabolism in the male hamster--2. Aromatization of androstenedione in the hypothalamus and in the cerebral cortex; kinetic parameters and effect of exposure to different photoperiods. AB - It has been demonstrated that exposure of the hamster to a short photoperiod (light on less than 12 h/day) induces an increased sensitivity of the hypothalamic-pituitary axis to the feedback effect of testosterone. It was consequently felt of interest to investigate whether the photoperiod might act by increasing the formation of estrogens in the CNS and/or in the anterior pituitary. The aromatase activity was studied utilizing a sensitive in vitro assay that measures the amount of 3H2O formed during the conversion of [1 beta 3H]androstenedione to estrone. First of all it has been investigated whether the aromatizing enzymes, previously found in the hypothalamus, were present also in the cerebral cortex and in the anterior pituitary; secondly, the kinetic parameters of the enzyme were determined; finally, the possible variation of the central aromatase activity in hamsters exposed to a long or to a short photoperiod was investigated. The results obtained indicate that both in the hypothalamus and in the cerebral cortex the aromatization of androstenedione is linear with respect to time of incubation and tissue concentration; moreover, in the two structures, the enzyme demonstrated a similar Michaelis-Menten constant (0.03 and 0.08 microM respectively). From a quantitative point of view, the hypothalamus seems to possess an aromatizing activity higher than that of the cerebral cortex. Exposure of the hamsters to a short photostimulation for 60 days resulted in a significant regression of the reproductive system (decreased testicular weight and serum LH levels) and in a decrease of the aromatase activity of the hypothalamus. There was no effect of the photoperiod on the aromatase of the cerebral cortex. Since androgens are known to stimulate the aromatase, the present data might be tentatively interpreted by suggesting that the variation in the formation of estrogens during the short photoperiod might be the consequence of the decreased serum testosterone levels typical of the hamster in the quiescent gonadal period. PMID- 2913404 TI - Evidence for kinetically distinct forms of corticosteroid 11 beta-dehydrogenase in rat liver microsomes. AB - In this paper we have characterized the 11 beta-dehydrogenase component of the 11 beta-hydroxysteroid dehydrogenase complex in rat liver microsomes. This enzyme oxidized cortisol and corticosterone to cortisone and 11-dehydrocorticosterone, respectively. Corticosterone was oxidized 10-20 times faster than cortisol to its 11-oxo product. In freshly isolated microsomes enzyme activity was partially suppressed. Exposure of the microsomes to detergent or to prolonged incubation (24 h) released latent enzyme activity. Latency release was dependent on steroid concentration. The pH-activity profiles of latent and stimulated enzymes differed in shape (concave vs convex) and in pH optimum (pH 10 vs pH 8.5-9.5). Magnitude of latency release was greatest at pH 7. Corticosterone was a potent inhibitor of cortisol oxidation, but cortisol inhibited corticosterone oxidation poorly. With cortisol or corticosterone as substrates, low and high Km species were found. The high Km form represented about 90% of total enzyme activity in untreated microsomes. When latency was released, the low Km form was not detected. Our results suggest that at least two isozymic forms of corticosterone 11 beta dehydrogenase reside in rat liver microsomes, or that a single enzyme coexists in two kinetically distinguishable forms. PMID- 2913405 TI - Kinetic studies of inhibition of estradiol 2- and 16 alpha-hydroxylases with 17 alpha-ethynyl and 17 beta-cyano steroids: preferential inhibition of the 16 alpha hydroxylase. AB - Substrate preference of estrogen 2- and 16 alpha-hydroxylases in male rat liver microsomes were determined by using estrone (E1) and estradiol (E2). Kinetic parameters of the hydroxylations showed that E2 is a better substrate for the hydroxylations than E1 and the preferences principally depend on the differences in Vmax values of the hydroxylations between the two substrates. Kinetic studies of inhibition of E2 2- and 16 alpha-hydroxylase activities in the male liver microsomes with ethynylestradiol (EE) and norethisterone (NET), the active ingredients in oral contraceptives, and 17 beta-cyano-16 alpha, 17 alpha-epoxy 1,3,5(10)-estratrien-3-ol were extensively carried out. All of the steroids competitively blocked the two activities and the 16 alpha-hydroxylation was preferentially inhibited by them. Kinetic data, the apparent Ki's for the inhibitors and the apparent Km's for the substrate E2 in the assay, demonstrated that EE and NET are very potent inhibitors for the 16 alpha-hydroxylase. On the other hand, when female rat liver microsomes were used as an enzyme source in the inhibition experiments, the two hydroxylase activities were not so affected by EE and NET and the preferential inhibition was not observed with the ethynyl steroids. PMID- 2913406 TI - Proceedings of the XIII meeting of the International Study Group for Steroid Hormones. (Rome, Italy, 30 November-2 December 1987). PMID- 2913407 TI - Sertoli cell proteins in the human seminiferous tubule. AB - It is well known that rat Sertoli cells in culture secrete both testis-specific proteins, such as inhibin and androgen binding protein (ABP), and proteins which are very similar, if not identical, to serum proteins, such as transferrin (TF), ceruloplasmin, and IGF-I. It is also well known that very few data have been reported about the secretory activity and the hormonal regulation of the Sertoli cell in man, mainly because of the difficulties associated with the isolation of pure cell populations from human tissue. Using histoimmunochemical techniques we tried to localize, with specific antisera, Sertoli cell proteins and, when possible, their receptors in the human testis. The results obtained with our Light Microscopy studies suggest that: (1) human Sertoli cells produce and/or store transferrin (TF), IGF-I, an albumin-like protein and ABP; (2) TF receptors are localized in spermatocytes and early spermatids and are absent in spermatogonia, in the cytoplasm of Sertoli cells and in differentiated spermatids; (3) IGF-I type I receptors are localized in the same germ cells and in the cytoplasm of Sertoli cells. The results obtained with our Electron Microscopy studies suggest that TF and IGF-I are internalized through a receptor mediated endocytosis mechanism both in Sertoli cells (basal compartment) and in germ cells (spermatocytes and early spermatids). PMID- 2913408 TI - A new look to the andropause: altered function of the gonadotrophs. AB - After being controversial for a long time, the age associated decline in plasma T levels and secretion in normal men is now generally accepted. Although most data point towards a primary testicular origin for the decline in Leydig cell function, other data point towards alterations at the hypothalamo-pituitary levels: T levels in elderly men are decreased notwithstanding an important secretory reserve of both LC and gonadotrophs. Nycthemeral variations in plasma T levels are significantly decreased in elderly men. The increase in immunoreactive LH levels is dysproportionate to the increase of bioactive LH levels. Study of the activity of the LHRH pulse generator in 27 young and 21 elderly men revealed a significant decrease in frequency of high amplitude pulses for both LH and T. Moreover the sensitivity of the gonadostat to sex hormone feed back was significantly greater in the elderly men. Acute administration of an antiopoid (Naloxone), 2 mg i.v. both in young and elderly men at rest showed that in young and elderly men, Naloxone induced a comparable increase of LH levels. Naltrexone on the other hand increased LH pulse frequency in elderly but not in young men. The data show that opioids maintain their inhibitory effect on LHRH secretion in elderly men and suggest either that the opioid tone in the elderly men is decreased or that the response of the gonadotrophs to LHRH is decreased. PMID- 2913409 TI - Regulation of gonadotropin-stimulable adenylyl cyclase of the primate corpus luteum. AB - In an effort to understand the molecular mechanisms that control luteal function in the human and nonhuman primates, we have investigated the experimental conditions for expression of gonadotropin-induced adenylyl cyclase (AC) in membrane particles from primate corpus luteum (CL) and some of the factors modulating the enzyme activity. We also examined the usefulness of the cell-free model for studying the role of AC in the regulation of CL functions in human and nonhuman primates. Enzyme activity was dependent on guanine nucleotide and Mg ion. Dose-response curves showed that the AC activation constants for hCG was about 0.1 microgram/ml. This value did not shift after the addition of guanine nucleotide. Enzyme responsiveness to prostaglandin E2 was small and, in contrast to a number of other nonprimate species, AC from the human CL was not stimulated by catecholamines. Calcium directly inhibited responsiveness of hCG-sensitive AC; inhibition was significant at 0.5 mM CaCl2 (in the presence of 1 mM EDTA and 2 mM ATP), being 90% at 2.5 mM CaCl2. These results support the concept that Ca2+ might play a role in the regulation of gonadotropin action and life span of human CL. Changes in AC activities during luteal phase and pregnancy were similar in the CL of monkeys and humans. Thus, in both cases, maximal gonadotropin responsiveness was observed during the midluteal phase. Also, during pregnancy (term and early pregnancies), responsiveness to exogenous hCG in vitro was very low, but the enzyme was readily responsive to NaF (10 mM) and forskolin (100 microM). These activities suggest that the tissue remains functionally active during pregnancy. It is concluded that the cell-free AC system is an effective model to study the cellular mechanisms that regulate luteal function in human and nonhuman primates. PMID- 2913411 TI - A new form of the syndrome of apparent mineralocorticoid excess. AB - The syndrome of apparent mineralocorticoid excess combines the features of unexplained but spironolactone-correctable mineralocorticoid excess in association with a decreased rate of oxidation of cortisol to cortisone. No relationship was initially implied between the pathogenesis of the disorder and the metabolic disturbance as expressed by an elevated cortisol:cortisone metabolite ratio but the ratio itself has served as a biochemical marker for the disorder. Cortisol has been suggested as the mineralocorticoid in a setting of enhanced sensitivity to the steroid as a result of the incomplete oxidative metabolism of cortisol by the kidney. We present evidence that diminished conversion of cortisol to cortisone is not an obligatory mechanism in the syndrome of apparent mineralocorticoid excess. A form of the disorder is described, designated the Type 2 variant, in which all features are preserved except that the cortisol:cortisone metabolite ratio is normal. An essential feature of both variants, however, is a decrease in the cortisol metabolic clearance rate. These findings require a more generalized definition of the syndrome of apparent mineralocorticoid excess to include other deficient mechanisms of metabolic inactivation of cortisol. PMID- 2913410 TI - Identification and implications of new types of mineralocorticoid hypertension. AB - 200 patients with mineralocorticoid hypertension were studied at the Clinical Study Center. The study of 150 patients with primary aldosteronism revealed five distinct subsets based on their responses to the upright posture, after administration of intravenous saline, deoxycorticosterone acetate, and spironolactone. Two new types were identified--aldosterone producing responsive adenoma (AP-RA) and primary adrenal hyperplasia (PAH). Patients with AP-RA maintained normal physiologic responses to the above maneuvers. Patients with PAH had responses similar to patients with an aldosterone producing adenoma (APA) but no tumor was identified. Both types were cured by unilateral adrenalectomy. There has been no change in subtype in up to 20 years of follow-up. The notion of a continuum from low renin hypertension to APA is not supported. Primary deoxycorticosteronism caused by a benign adrenal adenoma, malignancy and hyperplasia is described. Uniquely, overproduction of the 17-deoxysteroids of the zona fasciculata occurs with normal 17-hydroxy function. After the removal of a benign adenoma the contralateral adrenal gland revealed a delay in the 17 deoxysteroid responses to ACTH in the face of normal cortisol increases. This suggests that an independent pituitary regulator of the 17-deoxypathway may exist. Other hypertensive disorders with excessive deoxycorticosterone production are linked with increases of ACTH and cortisol levels. The hallmarks of primary deoxycorticosteronism are hypertension with hypokalemia, suppression of renin and aldosterone, and overproduction of the 17-deoxysteroids. PMID- 2913412 TI - Antialdosterones: incidence and prevention of sexual side effects. AB - The use of spironolactone in the treatment of hypertension has been limited by the occurrence of sexual side effects, mainly menstrual disturbances in women and gynaecomastia in men. In order to minimize this limitation on the use of an effective potassium-sparing antihypertensive agent, two strategies can be proposed: (1) A decrease in the daily dose of spironolactone. In 182 patients with essential hypertension treated with spironolactone alone for a mean follow up period of 23 months, daily doses of 75-100 mg were as effective on blood pressure as doses of 150-300 mg. In contrast, the development of gynaecomastia- 91 cases among 699 men--was dose-related in 6.9% (50 mg/day) to 52.2% (150 mg or more/day) of the cases. (2) An improvement in the receptor-binding specificity of spironolactone. Three 9 alpha, 11 alpha-epoxy derivatives have been characterized in vitro in rats and in rabbits. They exhibited a 3- to 10-fold decrease of the antiandrogenic and progestagenic effect, compared with spironolactone. In humans, one of these derivatives counteracted the fall in urinary Na/K ratio induced by 9 alpha-fluorohydrocortisone at a 25 mg dose. PMID- 2913413 TI - [Increase in the number of severely sick and wounded at emergency health services in the inner city of Stockholm]. PMID- 2913414 TI - [Erroneous view on the humanities in medical education]. PMID- 2913415 TI - [By whom should patients at occupational health services be treated?]. PMID- 2913416 TI - [Anxiety neurosis or panic syndrome? The differences between mixing and linking definitions]. PMID- 2913417 TI - [Cholesterol: give an evaluation of non-pharmacologic treatment priority]. PMID- 2913418 TI - [Forgetfulness and lack of information are reasons why patients fail to appear]. PMID- 2913420 TI - [Childrens' situation in the world. The march forward has changed to a retreat]. PMID- 2913419 TI - [A growing research interest in liver sinusoidal cells]. PMID- 2913421 TI - SCC-RIA in the diagnosis of squamous cell carcinoma of the head and neck. AB - A reliable circulating tumor marker, appropriate for head and neck malignancy, is not yet available. This manuscript reports the efficacy of using circulating squamous cell carcinoma antigen in evaluating patients with squamous cell carcinoma of the head and neck. Serum samples from 89 patients with squamous cell carcinoma of the head and neck were obtained before treatment and at intervals following treatment. Squamous cell carcinoma antigen levels were determined by radioimmunoassay. Elevated pretreatment serum levels of squamous cell carcinoma antigen were identified in 39 of 89 patients (44%) who had head and neck squamous cell carcinoma. Of the 16 patients evaluated from this group with recurrent or persistent disease, 15 (93.5%) demonstrated elevated levels of squamous cell carcinoma antigen. However, of the 21 evaluable patients who remained disease free, only 10 (48%) had post-therapy levels within the normal range. The possible use of this marker in aiding the clinical follow-up of head and neck cancer patients is discussed. PMID- 2913422 TI - Laryngotracheal injury following cricothyroidotomy. AB - Airway complications following elective cricothyroidotomy were reviewed in 48 adult cardiothoracic surgery patients. A 52% incidence of airway complications was found and manifested by failed or delayed decannulation, extensive subglottic granulation tissue, stenosis, vocal cord paralysis, and aspiration pneumonia. The most common cause for decannulation difficulty was subglottic stenosis (50%). Several risk factors were specifically identified, including a period of cricothyroid cannulation exceeding 30 days, the presence of diabetes, and advanced age. These findings suggest that airway sequelae following cricothyroidotomy in cardiothoracic surgery patients is higher than previously reported. Indications and risk factors for cricothyroidotomy are discussed. PMID- 2913423 TI - Laser lingual tonsillectomy. AB - Diseases of the lingual tonsils are generally overlooked in both clinical practice and medical literature. Infections of the lingual tonsils are usually treated medically, although in patients with symptomatic chronic inflammation or hyperplasia of the lingual tonsils, surgical intervention may be indicated. Eighty-two patients with benign inflammatory problems of the lingual tonsils, who were not improved by medical management, underwent laser lingual tonsillectomy at four different medical centers, between 1984 and 1987. The procedure was tolerated well by all of the patients, with no significant operative complications. Short- and long-term results were satisfactory. Laser surgery is an effective method for the treatment of benign hyperplastic and inflammatory diseases of the lingual tonsils. PMID- 2913424 TI - Surgical management of severe laryngomalacia. AB - Infants and children with laryngomalacia exhibit varying degrees of upper airway obstruction and dysphagia. Although the disorder is usually self-limited, the potential exists for symptoms so severe that operative intervention cannot be avoided. Relief of progressive airway compromise traditionally has involved bypassing the obstruction with tracheotomy. Recently, endoscopic surgical management of the most severe cases has been reexamined by the authors and others. Thirteen infants and children underwent supraglottoplasty (also referred to as epiglottoplasty or partial arytenoidectomy) for severe, complicated laryngomalacia. Endoscopic laser removal of flaccid supraglottic tissue resulted in improvement of the airway in all patients. In most patients, associated symptoms improved or completely resolved. Supraglottoplasty is an effective alternative to tracheotomy in carefully selected patients with severe laryngomalacia. PMID- 2913425 TI - Paranasal sinus malignancy: a comprehensive update. AB - A retrospective analysis of 60 cases of paranasal sinus cancer in patients admitted between 1970 and 1985 was undertaken. Forty-six tumors originated in the maxillary sinus, and 14 originated in the ethmoid sinuses. Computed tomography, magnetic resonance imaging, and endoscopic sinus examination aided in early diagnosis of sinus cancer. Computed tomography aided in staging tumors; Caldwell Luc alone was inadequate for staging tumors invading deeper sites such as the orbits or pterygoid muscle. There were 15 early (T1 or T2) and 31 advanced (T3 or T4) maxillary sinus cancers. Multimodality therapy incorporated radiation, surgery, and chemotherapy. The 5-year survival rate was 49%. We prefer preoperative radiotherapy for advanced lesions and postoperative radiotherapy for early lesions. The use of preoperative radiation therapy has increased our globe salvage rate. All but one of the patients who developed recurrent disease showed recurrence at the primary site prior to developing regional or distant metastasis. Radiation therapy, combined with aggressive surgical management to remove all tumor, provided the best survival rates in advanced lesions. PMID- 2913426 TI - High-activity iodine-125 endocurietherapy for head and neck tumors. AB - Inoperable solid tumor recurrence within a surgical bed or within a previously irradiated field usually responds poorly to re-treatment with conventional external beam irradiation (EXRT) and/or chemotherapy. We present a new, alternative method of re-treatment used in two patients with recurrent head and neck cancer involving the parotid (adenocarcinoma) and neck nodes (squamous cell carcinoma). These patients were successfully re-treated with high-activity 125iodine (I-125) permanent implantation. PMID- 2913427 TI - Acoustic neuroma--the patient's perspective: subjective assessment of symptoms, diagnosis, therapy, and outcome in 541 patients. AB - Surgical treatment of acoustic neuroma has been reviewed in the medical literature, but assessment of outcome from the patient's perspective has received little attention. The Acoustic Neuroma Association (A.N.A.) is a large organization of acoustic neuroma patients which provides information and support services. This article reports the subjective assessment of symptoms, diagnosis, treatment, and outcome as evaluated by 541 A.N.A. members. This retrospective study presents an extensive overview of the experience of acoustic neuroma patients treated at a variety of institutions, and provides a unique perspective not previously represented in the medical literature. PMID- 2913428 TI - Stomal complications and airflow line problems of the Communi-Trach I cuffed talking tracheotomy tube. AB - There have been no reports of stomal complications and airflow line problems associated with a cuffed talking tracheotomy tube. However, the results of this study showed that stomal complications, in the form of pressure necrosis and wound extension, and problems with airflow line kinking occurred with a 40% and 80% frequency, respectively. Solutions to both difficulties are discussed. PMID- 2913429 TI - Alterations in glycoconjugate expression following malignant transformation of human oropharyngeal squamous mucosa. AB - Malignant transformation of the squamous mucosa in the human oropharynx may be accompanied by alterations in carbohydrate production. Glycoconjugate expression was assessed by examining lectin-binding patterns and ABH isoantigen expression in human biopsy specimens from nine cases of carcinoma in situ and ten cases of invasive squamous cell carcinoma as well as adjacent normal squamous mucosa. Ten different fluorescein-conjugated lectins were used. Each lectin binds to specific nonreducing end-terminal carbohydrate residues. Wheat germ agglutinin and peanut agglutinin displayed intense cytoplasmic and/or membrane binding in more than 90% of the carcinoma in situ and squamous cell carcinoma specimens. However, only 40% of normal squamous epithelium specimens displayed intense cytoplasmic and/or membrane binding with wheat germ agglutinin and peanut agglutinin. Bandieraea simplicifolia I and Helix pomatia exhibited weak binding in less than 35% of normal and neoplastic tissues. Weak canavalia ensiformis binding was identified infrequently in the superficial layers of normal squamous mucosa, but was not found in neoplastic epithelium. None of the cases displayed binding for Dolichos biflorus, Ulex europaeus I, Sophora japonica, Glycine maximus, or Ricinus communis. Monoclonal antibodies directed against ABH blood group isoantigens showed increased cytoplasmic immunoreactivity for anti-H in dysplastic and neoplastic tissues, when compared with normal squamous mucosa. These findings indicate that wheat germ agglutinin and peanut agglutinin and H isoantigen are useful markers of malignancy in squamoproliferative lesions of the oropharynx, apparently reflecting alterations in expression of N-acetyl-D-glucosamine and galactose-related sugars, which appear following malignant transformation. PMID- 2913430 TI - A porcine model for multiple musculocutaneous flaps. AB - The purpose of this study was to develop and describe in detail a reproducible porcine model for musculocutaneous flap study. The model was required to demonstrate the following: 1. consistent, easily identifiable anatomical landmarks for muscles and muscular vascular pedicles; 2. flap survival, consistent with the musculocutaneous perforator arrangement of blood supply; 3. ease of islanded- or free-flap formation; 4. arrangement of flaps on each animal, allowing paired studies of control and experimental flaps; and 5. a maximum number of flaps per animal, without undue morbidity or mortality. Pilot dissections were made of the pectoralis, trapezius, latissimus dorsi, gracilis, biceps femoris, and tensor fasciae latae muscles and their major vascular pedicles. After establishing the anatomical landmarks, we formed musculocutaneous flaps at each site to verify the above five requirements. A total of 72 muscle/vessel pedicle dissections were performed, incorporating formation of 61 island musculocutaneous flaps. The skin component overlying an islanded muscle block survived in 60 instances, confirming the reliability of the flap model. We concluded that five pairs of musculocutaneous flaps could be fashioned on one pig, using the bilateral control/experimental paradigm if desired. The pectoralis, latissimus dorsi, trapezius, gracilis, and biceps femoris muscles were used. The ventral muscle group (pectoralis, gracilis) was raised in one operating session, and the lateral muscles (trapezius, latissimus dorsi, biceps femoris) were raised in one further session per side. Three new porcine flaps are described--the pectoralis, biceps femoris, and trapezius. Morbidity was confined to mild splinting of the limbs for one day. This is also the first example of the use of ten musculocutaneous island flaps on one pig, and represents an opportunity for performing physiological, pathological, or pharmacological experiments on the musculocutaneous flap. PMID- 2913431 TI - Sandwich graft tympanoplasty: experience, results, and complications. PMID- 2913432 TI - The endoscopic approach to the sphenoid sinus. PMID- 2913433 TI - Computer-fabricated custom mandibular replacement prostheses. PMID- 2913434 TI - GIA stapler in radical neck dissection. AB - I have used this procedure for over 7 years on approximately 150 radical neck dissections and have experienced no complications related to the use of this stapler, and operative time has been reduced. Approximately one third of these neck dissections have been done on patients who later received radiation therapy. In addition, approximately one third received preoperative radiation therapy. No problems with increased complications or recurrences in the area where the staples remain have been noted. This procedure has been discussed with radiation therapists at the University of Florida, where most of the patients received radiation therapy, and no increase in the complication rate or recurrence rate in this area of the neck was noted. PMID- 2913435 TI - Laryngeal complications of intubation: GER. PMID- 2913436 TI - The effects on complement component 3 of dietary variation of protein, fat and vitamin E during growth of young mice. AB - Some studies have shown that nutrition lowers overall immunity to disease. To further elucidate the role of nutrition on immunity, we have investigated the effect on serum Complement C3 by three nutrients, protein, lipid and vitamin E, in BALB/c mice for up to 24 weeks. The group with high dietary vitamin E had slightly higher C3 for the first four months but by the 22nd week was lower than control. The groups receiving high or low protein had, respectively, high or low C3. Injection of thymosin fraction 5 increased the C3, suppressed by the low protein diet. The group on the high lipid diet had high C3 until the 14th week whereupon it declined to control level by the 22nd week. The low lipid diet resulted in low C3 during the early weeks but increased to control level by the 22nd week. We conclude that diet is important to complement mediated immunity of young mice. PMID- 2913437 TI - Caffeine-phenylethylamine combinations mimic the cocaine discriminative cue. AB - Twelve male Sprague-Dawley rats were trained in a two-choice, food reinforced, drug discrimination task utilizing 10 mg/kg cocaine and saline as discriminative stimuli. Subjects were tested for stimulus generalization with a wide range of cocaine doses and several dose combinations of caffeine, ephedrine, and phenylpropanolamine (CEP). Caffeine produced only partial generalization. The triple CEP combinations resulted in complete generalization at high doses. All drugs produced response rate decrements at high doses. These data clearly indicate that certain look-alike stimulant products mimic the cocaine cue. The present data parallel human self-report data regarding the similarity in subjective profiles between illicit cocaine and the legal look-alike stimulants. PMID- 2913439 TI - Society for Magnetic Resonance Imaging, seventh annual meeting. 25 February-1 March, 1989, Los Angeles, California. Abstracts. PMID- 2913438 TI - Problems associated with the application of the Cheng-Prusoff relationship to estimate atropine affinity constants using functional tissue responses. AB - We have studied problems associated with the application of the Cheng-Prusoff relationship to the estimation of atropine dissociation constants from isolated guinea-pig tracheal responses. The values obtained have been compared to dissociation constants derived using Schild analysis. It was observed that when either carbachol (an agonist of high efficacy) or pilocarpine (an agonist of low efficacy) was used the dissociation constants estimated for atropine using the Schild analysis were very similar to those estimated using the Cheng-Prusoff relationship. In these latter experiments the agonist concentration used was the EC80. When the agonist concentration used was increased to supramaximal concentrations (3-fold greater than the EC100) the dissociation constants derived were overestimations by approximately 10-fold. It is concluded that in certain circumstances the results obtained using both the Cheng-Prusoff relationship and Schild analysis are comparable. However, it is unlikely that the Cheng-Prusoff relationship is generally applicable and that Schild analysis is clearly preferable in determining antagonist dissociation constants. PMID- 2913440 TI - [Radionuclide diagnosis of disorders of the central lymph dynamics in thoracic duct pathology]. AB - The experience in using radiolymphography in the diagnosis of central lymph dynamics disorders in thoracic duct pathology has been analysed. For the first time in Soviet literature we encounter two observations over the state of lymph dynamics along the thoracic duct by means of lymphoscintigraphy with colloid 113mIn in patients with lymphangiectasia of the thoracic duct and chylothorax. In importance of lymphoscintigraphy in determining the compensatory mechanisms of the lymph flow in primary pathology of the main lymph collector is emphasized. PMID- 2913441 TI - [Comparative evaluation of the transport of transit hepatotropic compounds based on mathematical modelling]. AB - Specific features of kinetics by the hepatobiliary system 131I-BR, 131I-BS, 99mTc pVIDA and 99mTc-NIDA have been shown. There is a definite pattern for all coefficients: a1,2 greater than a2,1; a2,1 greater than a2,3 less than a3,4. In this case the phase of absorption (a1,2) six times exceeded that of isolation of an indicator from hepatocytes (a2,3). The main feature consists in the augmented speed of the passage of indicators through hepatocytes in the following sequence: 131I-BR----131I-BS----99mTc-pVIDA----99mTc-NIDA. A three-chamber reversible model is suitable for various hepatotropic compounds. PMID- 2913442 TI - [Nonspecific resistance during preoperative chemoradiation treatment and UHF hyperthermia of osteogenic sarcoma]. AB - The extent of metastatic spread and the life span depend on the level of nonspecific resistance of the body of patients with osteogenic sarcoma. Chemoradiation therapy reduces antitumoral resistance of patients, and the use of local UHF hyperthermia prevents this negative effect of complex treatment. PMID- 2913443 TI - [Intracavity thermo- and gamma-therapy of uterine cancer]. AB - Some methodological problems of the use of intracavitary UHF hyperthermia combined with intracavitary gamma-beam therapy in combined radiation therapy of uterine cancer patients are considered. Indications for the use of this method and radiobiological substantiation of thermoradiotherapy for this group of patients are discussed. The advantages of the proposed method of thermoradiotherapy have been noted on the basis of immediate clinical observations, endoscopic, x-ray and morphometric findings. PMID- 2913444 TI - [Combined radiation therapy of cervical cancer using a split course]. AB - The author studied the possibilities of combined radiation therapy conducted by a split (group I) and continuous course (group II) in 195 patients with neglected forms of cervix uteri cancer. The patients of the two groups were of the same age, had the same somatic diseases, the extent of the tumor spread and the anatomical and clinical forms of the tumor. The methods of radiotherapy used for them differed both in time and space parameters. The continuous course of treatment was presented as a conventional classic variant of radiotherapy, the split course included a break at a half of the focal cumulative dose brought to the tumor growth site. The author shows the advantages of the split method for the treatment of cervix uteri cancer. Indications for the split course of treatment are given. PMID- 2913445 TI - [Morphometric research in determining the absorbed dose in the lungs formed from aspirated radionuclides]. AB - Macro- and microtopography of the distribution of aspirated colloidal 144CeF3 in autographs of rabbit lung total sections were examined with the help of a monitoring-measuring device "Videoplan" and microcomputer. Quantitative assessment of photoemulsion-blackening areas at the site of radionuclide concentration has confirmed that aspirated radionuclides are distributed in the lungs according to the same laws as nonradioactive aerosols: the relation of total microvolumes of actually irradiated pulmonary tissue to the entire lung volume long after radionuclide entry is shown; a possibility to use these data for determination of an actually absorbed dose in microvolumes of pulmonary tissue during aspiration of radionuclides is considered. PMID- 2913446 TI - [Test monitoring as a form of controlling student cognitive activities]. AB - A test control of the initial, intermediate and the final level of knowledge of the course and a test control of the level of acquisition of the knowledge on radionuclide diagnosis were made in 179 students of the Therapy faculty. This form of the test allows one to evaluate the level of self-training, efficiency of the studies and the level of the knowledge of the course and its consolidation. The test control helps reveal problems and themes most difficult for mastering. The test control can be used for raising the efficiency of studies at all stages. PMID- 2913447 TI - [Functional activity of the thyroid during radiation therapy of cervical cancer]. PMID- 2913448 TI - [Metastasis of penile cancer to the ischial bone]. PMID- 2913449 TI - [The organization of roentgenologic and radiologic research in the USA (based on the data from a scientific mission)]. PMID- 2913450 TI - If dancers ate their shoes: inductive reasoning with factual and counterfactual premises. AB - This experiment addressed the effect of precue information, which may be either familiar or novel, and either relevant or irrelevant, on the solution of inductive reasoning problems. Sixty undergraduate students each completed 216 verbal inductive reasoning problems and five psychometric ability tests. The reasoning problems were equally divided among analogies, classifications, and series completions, with half of each kind of item presented in a standard, uncued format, and half presented with a precue. With respect to internal validation, it was found that for analogies and classifications, subjects take longer to process irrelevant than relevant information if the precue is familiar, but they take longer to process relevant than irrelevant information if the precue is novel. For series completions, this relation does not hold; rather, both novelty and irrelevance add time to the processing of information, with the time for irrelevance greater than that for novelty. The utility of precues for different tasks was explored, and it was found that familiar relevant precues facilitated solution of the more difficult kinds of items (classifications and series completions), but hampered solution of the easier, more automatically solved items (analogies). With respect to external validation, it was found that the nonentrenched induction tasks overlapped with psychometric tests in terms of abilities measured, that the abilities measured were fluid rather than crystallized, and that the precued (more nonentrenched) items were better measures of fluid abilities than were the uncued items. PMID- 2913451 TI - Word attributes and lateralization revisited: implications for dual coding and discrete versus continuous processing. AB - Three attributes of words are their imageability, concreteness, and familiarity. From a literature review and several experiments, I previously concluded (Boles, 1983a) that only familiarity affects the overall near-threshold recognition of words, and that none of the attributes affects right-visual-field superiority for word recognition. Here these conclusions are modified by two experiments demonstrating a critical mediating influence of intentional versus incidental memory instructions. In Experiment 1, subjects were instructed to remember the words they were shown, for subsequent recall. The results showed effects of both imageability and familiarity on overall recognition, as well as an effect of imageability on lateralization. In Experiment 2, word-memory instructions were deleted and the results essentially reinstated the findings of Boles (1983a). It is concluded that right-hemisphere imagery processes can participate in word recognition under intentional memory instructions. Within the dual coding theory (Paivio, 1971), the results argue that both discrete and continuous processing modes are available, that the modes can be used strategically, and that continuous processing can occur prior to response stages. PMID- 2913452 TI - The belief-bias effect in the production and evaluation of logical conclusions. AB - In this study, we examined whether adult subjects' beliefs regarding the empirical truth of a conclusion affected their production as well as their evaluation of a logical conclusion in a reasoning task. In addition, the relation between the ability to resolve an abstract reasoning problem correctly and the effect of belief-bias was examined. The subjects were given one of four paper-and pencil reasoning tasks, two of them using an evaluation paradigm, and two of them using a production paradigm. Each paradigm comprised either neutral problems or belief problems. The neutral problems were constructed to be as similar as possible to the belief problems, in order to control for extraneous factors. All four tasks also included an abstract reasoning problem. The results indicate a significant belief-bias effect for both the evaluation and the production tasks. Qualitative analysis indicated that the belief-bias effect was more pervasive in the production condition. In addition, the belief-bias effect was found to exist independently of the subjects' abstract reasoning ability. The results are discussed with reference to a two-stage model, in which belief is used to resolve uncertainties in inferentially produced conclusions. PMID- 2913453 TI - The role of expectancy in comparative judgments. AB - Researchers interested in the processing of relational information have sought a satisfactory explanation for the congruity effect in linear orders. It is relatively easy to select either the greater of two objects that are high on a dimension or the lesser of two objects that are low on a dimension, but it is relatively difficult to determine the greater of two objects that are low in magnitude or the lesser of two objects that are high in magnitude. One explanation of the congruity effect is the expectancy hypothesis that claims that the choice of the comparative primes objects of particular magnitudes. We present two experiments that demonstrate that a congruity effect of equivalent magnitude is obtained when the comparative is presented after the stimulus pair. Moreover, this equivalence cannot be attributed to the salience of the dimensions we employed, because this equivalence held for stimuli that were classified as salient and for those classified as nonsalient. These findings are interpreted in the context of some current explanations of the congruity effect. PMID- 2913454 TI - Selectional processes in causality judgment. AB - Two experiments illustrate the way in which competition between potential causes occurs when subjects are asked to judge the extent to which an action is the cause of an outcome. In the first experiment, it was found that introducing occurrences of the outcome in the absence of the action reduced causality judgments, but this effect was attenuated if these outcomes were signaled by another stimulus. In the second experiment, a delay between the action and the outcome reduced judgments, but this could be abolished by inserting a stimulus between the action and the outcome. The results are discussed in terms of a view of causality judgment that assumes that such judgments are based on associations between the mental representations of the action and the outcome. PMID- 2913455 TI - Unconscious processing of dichoptically masked words. AB - In three experiments, the subjects' task was to decide whether each of a series of words connoted something good (e.g., fame, comedy, rescue) or bad (stress, detest, malaria). One-half second before the presentation of each such target word, an evaluatively polarized priming word was presented briefly to the nondominant eye and was masked dichoptically by either the rapidly following (Experiment 1) or simultaneous (Experiments 2 and 3) presentation of a random letter-fragment pattern to the dominant eye. (The effectiveness of the masking procedure was demonstrated by the subjects' inability to discriminate the left vs. right position of a test series of words.) In all experiments, significant masked priming effects were obtained; evaluative decisions to congruent masked prime-target combinations (such as a positive masked prime followed by a positive target) were significantly faster than those to incongruent (e.g., negative prime/positive target) or noncongruent (e.g., neutral prime/positive target) combinations. Also, in two of the three experiments, when subjects were at chance accuracy in discriminating word position, their position judgments were nevertheless significantly influenced by the irrelevant semantic content (LEFT vs. RIGHT) of the masked position-varying words. The series of experiments demonstrated that two very different tasks--speeded judgment of evaluative meaning and nonspeeded judgment of word position--yielded statistically significant and replicable influences of the semantic content of apparently undetectable words. Coupled with previous research by others using the lexical decision task, these findings converge in establishing the reliability of the empirical phenomenon of semantic processing of words that are rendered undetectable by dichoptic pattern masking. PMID- 2913456 TI - Detection of intraword and interword letter repetition: a test of the word unitization hypothesis. AB - Do words, as familiar units or gestalts, tend to swallow up and conceal their letter components (Pillsbury, 1897)? Letters typically are detected faster and more accurately in words than in nonwords (i.e., scrambled collections of letters), and in more frequent words than in less frequent words. However, a word advantage at encoding, where the representation of the string is formed, might compensate for, and thus mask, a word disadvantage at decoding and comparison, where the component letters of the representation are accessed and compared with the target letter. To better reveal any such word disadvantage, a task was used in this study that increased the amount of letter processing. Subjects judged whether a letter was repeated within a six-letter word or a nonword (Experiment 1; intraword letter repetition) or was repeated between two adjacent unrelated six-letter words or nonwords (Experiment 2; interword letter repetition). Contrary to Pillsbury's word unitization hypothesis, both types of letter repetition (intraword and interword) were detected faster and just as accurately with words as with nonwords. In Experiment 2, however, interword letter repetition was detected less accurately on common words (but not on rare words or third-order pseudowords) than on the corresponding nonwords. Thus, although the familiar word does not deny access to its own component letters, it does make their comparison with letters from other words more difficult. PMID- 2913457 TI - Speakers' assumptions about the lexical flexibility of idioms. AB - In three experiments, we examined why some idioms can be lexically altered and still retain their figurative meanings (e.g., John buttoned his lips about Mary can be changed into John fastened his lips about Mary and still mean "John didn't say anything about Mary"), whereas other idioms cannot be lexically altered without losing their figurative meanings (e.g., John kicked the bucket, meaning "John died," loses its idiomatic meaning when changed into John kicked the pail). Our hypothesis was that the lexical flexibility of idioms is determined by speakers' assumptions about the ways in which parts of idioms contribute to their figurative interpretations as a whole. The results of the three experiments indicated that idioms whose individual semantic components contribute to their overall figurative meanings (e.g., go out on a limb) were judged as less disrupted by changes in their lexical items (e.g., go out on a branch) than were nondecomposable idioms (e.g., kick the bucket) when their individual words were altered (e.g., punt the pail). These findings lend support to the idea that both the syntactic productivity and the lexical makeup of idioms are matters of degree, depending on the idioms' compositional properties. This conclusion suggests that idioms do not form a unique class of linguistic items, but share many of the properties of more literal language. PMID- 2913458 TI - Back to Woodworth: role of interlopers in the tip-of-the-tongue phenomenon. AB - When a person reports that a word is on the tip of his or her tongue, that person often recalls instead another word that is similar in sound to the target word. Two opposite roles have been suggested for these interlopers. An older view (Woodworth, 1929) holds that they are instrumental in the development of tip-of the-tongue (TOT) states because they obstruct successful retrieval of intended targets. A more recent view (R. Brown & McNeill, 1966) holds, on the other hand, that interlopers tend to nullify TOT states by facilitating complete retrieval of the intended targets. A study is reported in which participants were explicitly presented with interloper words. The results provide two planks of support for Woodworth's hypothesis. First, more TOT states occurred when the interloper was similar in sound to the target than when it was not. Second, more TOT states occurred when the interloper was presented at the actual time of retrieval than when it was presented earlier. It appears that interlopers tend to induce TOT states by obstructing retrieval, rather than to nullify them by facilitating retrieval. PMID- 2913459 TI - Correlational analyses of explicit and implicit memory performance. AB - Sixty-four subjects were administered two tests of explicit memory (selective recall and recognition) and four tests of implicit memory (identification in a perceptual clarification procedure, word-fragment completion, tachistoscopic identification, and anagram solution). Each test drew on a different subset of a long list of previously displayed words. Although the four implicit memory tests showed sizable priming effects, correlational and factor analyses showed striking dissociations. On the one hand, performance on the perceptual clarification procedure and word-completion tests were related to one another, as well as to recall and recognition. On the other hand, performance on tachistoscopic identification and anagram solution were related to one another, but not to the measures for the other tasks. A framework is proposed to reconcile these new results with current knowledge on the explicit/implicit memory distinction, based in particular on studies of amnesic subjects. It is argued that a small number of tasks, especially tachistoscopic identification, may serve as relatively uncontaminated and ubiquitous indicators of implicit memory. However, explicit remembering could affect performance in so-called implicit memory tasks that allow for a strategy of controlled selection of candidate responses from accumulating cues, in experimental conditions that make the explicit remembering of relevant events possible. PMID- 2913460 TI - Imagery, memory, and size-distance invariance. AB - The size-distance invariance hypothesis (SDIH) was examined for remembered and imaged stimuli. In Experiment 1, subjects gave remembered and imaged distances of familiar objects and imaged distance of nondescript rods. The relationship between stated size and distance is more adequately described by power functions with exponents less than 1 than by the more restricted SDIH (exponent of 1). In Experiment 2, subjects gave distance estimates to recalled and imaged familiar objects and described the visual context in which each object was situated. A different group then sorted the contexts into categories based on general similarity. There were no significant differences between distance estimates based on memory and those based on imagery, and the visual contexts were not sorted according to whether they were generated in the memory or in the imagery conditions. In Experiment 3, subjects estimated the distances to objects in an outdoor setting. A linear relationship was found between estimated and physical distance, suggesting that the lower exponents obtained in Experiments 1 and 2 were not artifacts of the distance judgment procedure. PMID- 2913461 TI - The properties of retrieval cues constrain the picture superiority effect. AB - In three experiments, we examined why pictures are remembered better than words on explicit memory tests like recall and recognition, whereas words produce more priming than pictures on some implicit tests, such as word-fragment and word-stem completion (e.g., completing -l-ph-nt or ele----- as elephant). One possibility is that pictures are always more accessible than words if subjects are given explicit retrieval instructions. An alternative possibility is that the properties of the retrieval cues themselves constrain the retrieval processes engaged; word fragments might induce data-driven (perceptually based) retrieval, which favors words regardless of the retrieval instructions. Experiment 1 demonstrated that words were remembered better than pictures on both the word fragment and word-stem completion tasks under both implicit and explicit retrieval conditions. In Experiment 2, pictures were recalled better than words with semantically related extralist cues. In Experiment 3, when semantic cues were combined with word fragments, pictures and words were recalled equally well under explicit retrieval conditions, but words were superior to pictures under implicit instructions. Thus, the inherently data-limited properties of fragmented words limit their use in accessing conceptual codes. Overall, the results indicate that retrieval operations are largely determined by properties of the retrieval cues under both implicit and explicit retrieval conditions. PMID- 2913462 TI - Metabolism of branched-chain amino acids in leg muscles from tail-cast suspended intact and adrenalectomized rats. AB - Degradation of branched-chain amino acids was studied in muscles of unloaded hind limbs from rats subjected to six days of tail-cast suspension. The total production of 14CO2 from uniformly labeled 14C-leucine, isoleucine, or valine, and the fluxes through leucine aminotransferase and alpha-ketoisocaproate dehydrogenase, which were measured using L-1-14C-leucine, were generally greater in the soleus and extensor digitorum longus muscles of unloaded than of weight bearing hind limbs. Adrenalectomy abolished any difference in flux through the aminotransferase, whereas the administration of cortisol to adrenalectomized animals restored the greater flux in the unloaded soleus muscle. Adrenalectomy partially diminished the greater flux through alpha-ketoisocaproate dehydrogenase in the unloaded soleus, whereas cortisol (2 mg/100 g body weight) treatment increased this difference. In the extensor digitorum longus, adrenalectomy abolished the differences in both enzyme fluxes due to hind limb suspension. In this muscle, cortisol treatment increased these fluxes to a similar extent in both weight-bearing and suspended, adrenalectomized animals so that the normal difference was not restored. These results suggest that leucine catabolism in hind limb muscles of suspended rats was influenced primarily by increased circulating glucocorticoid hormones, which are elevated twofold to fourfold in these animals. PMID- 2913463 TI - Ethanol: relative fuel value and metabolic effects in vivo. AB - A nasogastric formula infusion method was used to evaluate the steady-state fuel value of ethanol relative to that of glucose in eight chronically alcoholic men undergoing a 4- or 5-week balance experiment. Each subject received a maintenance infusion of the formula diet throughout the study. When control formula glucose (week 1) was isocalorically replaced with ethanol [week 2, 30% of kcal; week 3 or 4 (5-week experiment) 40% to 60% of kcal], the following was observed: weight loss; zero energy balance and reduced or negative balances of N, K, P, Mg, and Na; increased urinary urea N and 3-methylhistidine; lowered urinary C-peptide; no change in indirectly or directly measured thermal energy losses; and a blood level related rise in breath and urinary ethanol losses. All of these changes promptly reversed during the middle (week 3 in 5-week experiment) and final control weeks. Accounting for all diet-related energy losses (urine, breath, thermal), the fuel value of the ethanol-containing diet relative to the glucose control formula varied between 0.95 and 0.99, depending upon the blood alcohol level. Hence weight loss during short-term (seven-day) ethanol infusion is unrelated to overall negative energy balance, stems primarily from decrements in protein, minerals, and fluid, and may in part be mediated by the reduction in insulin secretion that accompanies switching from dietary glucose to ethanol. PMID- 2913464 TI - Serum cholestanol and plant sterol levels in relation to cholesterol metabolism in middle-aged men. AB - Serum cholestanol was studied in relation to fecal cholestanol excretion and cholesterol metabolism in a random middle-aged population of 61 men. The serum concentrations of cholestanol ranged from 1.6 to 10.8 mumol/L and were positively correlated with those of serum total LDL and HDL cholesterol. In terms of millimole per mole of cholesterol, these correlations disappeared; inverse associations were found with VLDL cholesterol and triglyceride levels, the P/S ratio of dietary fat, and the amount of fecal plant sterols, but not with fecal cholestanol. The serum contents of cholestanol (1) were also closely positively associated with those of serum plant sterols (campesterol and sitosterol) and fractional cholesterol absorption, (2) were inversely related to the fecal excretion of neutral sterols and cholesterol synthesis which were measured either by the sterol balance technique or serum cholesterol precursor sterols (desmosterol and lathosterol), and (3) were unrelated to bile acid synthesis. Fecal cholestanol (mean = 12.5 mg/d) was (1) clearly higher than the dietary cholestanol intake (less than 2 mg/d), (2) unrelated to serum cholestanol, and (3) positively correlated with the intestinal cholesterol (dietary plus endogenous) flux as well as fecal plant sterols, neutral sterols, and bacterial products of cholesterol. The study emphasizes that, in normal men, high serum cholestanol levels reflect high efficiency of intestinal sterol absorption and low cholesterol synthesis. Thus, the changes in the serum contents of cholestanol are parallel with those of plant sterols and opposite to those of cholesterol precursor sterols. PMID- 2913465 TI - Effects of ethanol on glucose turnover in pregnant rats. AB - Glucose turnover was measured in term pregnant rats fed ethanol (30% of caloric intake) throughout gestation. Ethanol ingestion significantly reduced maternal weight gain and term fetal body weight when compared to pair-fed or ad libitum fed controls. At term the blood glucose level and 6-3H-glucose turnover were reduced when compared to either control group. The rate of gluconeogenic recycling, indicated by the difference between 6-3H and 6-14C-glucose turnover determinations, was reduced by ethanol ingestion to half that of the control groups. Glucose turnover correlated with both conceptus weight and blood glucose level. Impaired maternal glucose homeostasis, including a reduced gluconeogenic response to the metabolic demands of late pregnancy, may thus contribute to the effects of ethanol on intrauterine growth. PMID- 2913466 TI - Measurement of the subcutaneous fat in the distal forearm by single photon absorptiometry. AB - The influence of subcutaneous fat on single photon (125I) absorptiometry (SPA) measurement of bone mineral content of the distal forearm was investigated. A fat correction model was tested by measurements on eight lean subjects with different amounts of porcine fat around their forearm, and further validated from measurements on 128 females. In addition, it is shown that the fat content in the distal forearm can be measured by SPA with a short-term precision at 1.9% in an obese subject and that it correlates well with total body fat (r2 = .7) measured by dual photon absorptiometry, skinfold thickness (r2 = .5), and body mass index (r2 = .6). By using this method in a double-blind placebo-controlled trial, hormonal substitutional therapy significantly decreased the forearm fat content without affecting the body weight in postmenopausal osteoporotic women. PMID- 2913467 TI - Influence of growth hormone (GH) on natural killer (NK) activity in women with impaired endogenous growth hormone secretion. PMID- 2913468 TI - Fluorescence microscopy of living cells in culture. Part A. Fluorescent analogs, labelling cells, and basic microscopy. PMID- 2913469 TI - A fluorescent derivative of ceramide: physical properties and use in studying the Golgi apparatus of animal cells. PMID- 2913470 TI - Bone marrow biopsy in the initial staging of Hodgkin's disease. AB - Results of bone marrow biopsy were retrospectively evaluated in 120 previously untreated patients with Hodgkin's disease. The incidence of bone marrow involvement was 13%. All patients with marrow invasion had B symptoms and/or clinically advanced disease. When patients with bone marrow involvement were compared to those without there were significant differences in the incidence of B symptoms, the clinical stage, hemoglobin levels, leukocyte counts, platelet counts, and serum levels of lactate dehydrogenase and alkaline phosphatase. None of 59 patients with clinical stage IA and IIA had evidence of marrow invasion. This study demonstrates that trephine bone marrow biopsy is of value in detecting marrow involvement in specific subgroups of untreated patients with Hodgkin's disease, i.e., those patients with constitutional symptoms and/or clinical stage III or IV. However, bone marrow biopsy adds little to the initial staging of patients with clinical stage IA and IIA. Routine use of this procedure in such patients may be unnecessary. PMID- 2913471 TI - Long-term survival after chemoradiotherapy for locally advanced squamous cell carcinoma of the esophagus. AB - Seven patients with locally far-advanced, inoperable, squamous cell cancer of the esophagus were given two cycles of concurrent radiation and chemotherapy. Each cycle consisted of 5-fluorouracil 1,000 mg/m2/day given as a continuous intravenous infusion over 96 hours, cisplatin 75 mg/m2 given as an intravenous bolus on day 1, and methotrexate 40 mg/m2 given as an intravenous bolus on days 8 and 15. Three thousand rads of radiation were given in 15 fractions between days 1 and 19. Six patients are evaluable for response. Symptomatic relief was obtained by all six and was complete in 4. Five patients achieved a complete response, and two remain alive and disease free. Five of the six evaluable patients survived for at least 12 months. Aggressive chemoradiotherapy may result in significant survival prolongation and symptomatic palliation in this poor prognosis subset of patients with esophageal cancer. PMID- 2913472 TI - Poor-risk non-lymphoblastic lymphoma of childhood: results of an intensive pilot study. AB - Children with "poor-risk" nonlymphoblastic lymphoma, especially those with marrow or nervous system (CNS) involvement at presentation, have fared poorly even on aggressive chemotherapy regimens. We report here the results of a pilot study of 30 children treated with a highly intensive chemotherapy regimen. This regimen includes an intensive Induction Phase consisting of three cycles of CHOP therapy (cyclophosphamide, doxorubicin, vincristine, and corticosteroids) as well as intensive intrathecal therapy with each cycle. This is followed by a CNS Consolidation Phase consisting of a single cycle of CHOP therapy with five intrathecal doses of "triple" chemotherapy (methotrexate, cytosine arabinoside, and hydrocortisone). Thereafter, a Maintenance Phase consists of alternating cycles of 1) cytosine arabinoside and 6-thioguanine, 2) oral methotrexate and VP 16, and 3) CHOP, for a duration that varied from 36 to 72 wk. Neither debulking surgery nor radiation therapy were recommended. There were 20 patients with Stage III disease (St. Jude's Staging System) and an additional ten patients with bone marrow and/or CNS involvement. The latter group included six patients with B-cell leukemia, three of whom also had CNS disease at presentation. Two additional patients had CNS disease without marrow involvement. Twenty-nine of 30 patients achieved a complete response. Six patients died with recurrent or progressive disease. Twenty-three patients are alive without any adverse events between 21 and 65 mo after diagnosis, with the median time of survival not yet reached (at least 32 mo). All seven adverse events occurred within 7 mo of diagnosis. Event free survival for all patients is 77%, for Stage III patients is 80%, and for patients with marrow and/or CNS involvement is 70%. This pilot study offers encouragement for improvement in the prognosis of children with "poor-risk" nonlymphoblastic lymphoma and merits evaluation in a Phase III randomized trial in the multicenter cooperative group setting. PMID- 2913473 TI - Rhabdomyosarcoma, presenting as disseminated malignancy from an unknown primary site: a retrospective study of ten pediatric cases. AB - From 1962-1984, ten children were referred to St. Jude Children's Hospital with a metastatic poorly differentiated malignancy; extensive diagnostic workup had failed to disclose the site of the primary tumor. Multiple skeletal metastases as well as bone marrow involvement were common findings. Erythrocytes were detected in the cytoplasm of tumor cells in several cases, and cytochemical stains confirmed that these phagocytic cells did not have features of mononuclear phagocytes. Establishing a pathologic diagnosis in these cases was difficult, and most special studies including cytochemistry and electron microscopy were not helpful in elucidating the diagnosis. A diagnosis of rhabdomyosarcoma was made at presentation in six cases. In the remaining cases, the diagnosis of rhabdomyosarcoma was subsequently made after rebiopsy of new tumor masses during the course of the illness, by ultrastructural examination of a cell line derived from the tumor or at postmortem examination. Based on initial symptoms, clinical features, and postmortem findings, the primary tumor sites were assumed to be in the middle ear, paravertebral area, base of skull, retrobulbar space, chest wall, and retropancreatic area. In four patients the disease was confined to bone marrow, lymph nodes, and meninges so that a primary site could not be assigned. The approach to pediatric patients presenting with disseminated malignancy from an occult primary site should consist of an aggressive pursuit of a specific diagnosis and establishment of a primary site to better direct therapy, particularly for those children whose tumors may be responsive to specific therapy. PMID- 2913474 TI - Late relapses after treatment for acute lymphoblastic leukemia in childhood: a population-based study from the Nordic countries. AB - Seven late relapses of acute lymphoblastic leukemia occurring 5.5 to 12.3 years after cessation of therapy are reported in 986 patients who had discontinued treatment for leukemia acquired before the age of 15. The study covers patients from the five Nordic countries. Of the 434 patients with ALL who had passed 5 years of follow-up without recurrence, seven have subsequently relapsed so far; an estimated cumulative proportion of 6.9% within the 10 years. In addition, we report a girl 15.9 years old at diagnosis who relapsed 7.3 years after cessation of therapy. These findings confirm that "cure" of acute lymphoblastic leukemia treated in the 1970s cannot be considered definite, even 5 years after discontinuation of therapy. PMID- 2913475 TI - Enhanced cis-platinum ototoxicity in children with brain tumours who have received simultaneous or prior cranial irradiation. AB - We report on four children who received cis-platinum simultaneously with, or in one case 10 months after, cranial irradiation and experienced exaggerated ototoxicity affecting all audible frequencies. The hearing loss was severe, affecting the critical areas for speech perception, and necessitated the provision of bilateral hearing aids. The audiograms of these patients are shown and compared to those of four children who had received cis-platinum as part of their treatment for neuroblastoma but without cranial irradiation. The precipitation of the exaggerated hearing loss with the administration of cis platinum in one patient 10 months after finishing cranial irradiation suggests that care should be taken in the timing of cis-platinum administration in relation to concurrent or previous cranial irradiation. PMID- 2913476 TI - Renal cell carcinoma in childhood. PMID- 2913477 TI - Response of agranulocytosis to thymectomy in a patient with thymoma and chronic lymphocytic leukemia. AB - A patient with chronic lymphocytic leukemia presented with recurrent episodes of severe neutropenia. This neutropenia was initially responsive to prednisone but eventually became refractory. A spindle-cell thymoma was diagnosed and resected with dramatic improvement in his granulocytopenia. Both autologous and heterologous granulocyte macrophage colony growth were clearly inhibited by the patient's serum. This is the first reported case of severe granulocytopenia associated with a thymoma that seemed to be reversed following thymectomy. PMID- 2913478 TI - Chemotherapeutic management of epidural neuroblastoma. AB - Nine children with neuroblastoma and spinal cord compression were managed initially with chemotherapy induction without laminectomy or radiotherapy. Of the nine children seven are neurologically normal, one has minimal residual deficits, and one remains paraplegic. The excellent results in these children, plus nine patients previously reported, emphasizes the validity of this approach in children with epidural extension of neuroblastoma. PMID- 2913479 TI - Combination chemotherapy for adrenal carcinoma: response in a 5 1/2-year-old male. AB - Adrenocortical carcinoma is an uncommon tumor of childhood, and systematic studies of therapeutic options are not available. Children with very large tumours have a poor outlook with surgery alone, so that other treatment should be considered, but the literature is unhelpful in suggesting what this should be. In the case reported here, combination chemotherapy, including cisplatinum, gave a well-documented good partial response, suggesting a possible role for adjuvant chemotherapy using such a drug combination. PMID- 2913481 TI - Phase II trial of amsacrine in patients with multiple myeloma. AB - Seventy-four previously treated patients with multiple myeloma were treated with Amsacrine (m-AMSA) 120 mg/m2 every 3 weeks. A good response was observed in two patients (3%), and improvement was seen in three patients (4%). Severe toxicity was observed in 33% of patients who received three or more courses of treatment. This dose and schedule of m-AMSA in multiple myeloma is usually ineffective. PMID- 2913480 TI - 123I-metaiodobenzylguanidine scintigraphy of ectopic intracranial retinoblastoma. AB - Radioiodinated metaiodobenzylguanidine (MIBG) has been used for diagnostic purposes to image neural crest tumors. We report the uptake of 123I MIBG in a child with ectopic intracranial retinoblastoma. It is felt that 123I MIBG scintigraphy may have a role in detecting occult metastatic disease in these patients. PMID- 2913482 TI - Wide-field radiation therapy plus simultaneous chemotherapy for refractory Hodgkin's disease. AB - Nine male patients with disseminated Hodgkin's disease who had relapsed and/or were refractory to two or more non-"cross-resistant" programs of combination chemotherapy (range, two to five previous programs; median, three) were admitted into a study of treatment with wide-field low-dose radiation therapy (2,000 cGy), to all lymph node bearing areas, the liver, the spleen, and in selected cases the lungs (1,000 cGy). Simultaneous with each course of radiation therapy, chemotherapy with BCNU and procarbazine given at 50% doses of a known program of chemotherapy (BOPP) with vincristine and prednisone was given. Treatment was completed in five patients. Three of these achieved a complete remission; the other two had a partial response. Of the other four, two died during treatment with interstitial pneumonitis (probably radiation induced), and two failed to respond. Remission durations were 18+, 38, and 44+ months. Pulmonary toxicity was severe; however, hematologic and other toxicities were acceptable. The incorporation of wide-field low-dose radiation should be considered in programs of rescue for patients with Hodgkin's disease who relapse or are refractory to standard combination chemotherapy. PMID- 2913484 TI - Estimation of ligand binding parameters by simultaneous fitting of association and dissociation data: a Monte Carlo simulation study. AB - A new procedure for analysis of ligand binding kinetics was evaluated by Monte Carlo simulations. In this, all association and dissociation data were fitted simultaneously to a set of nonlinear equations. This should have several advantages over more conventional methods; data are better used in a single fitting procedure in which the degrees of freedom are maximized and the error term is spread over more observations; all relevant parameters (Bmax, k1, and k 1) are obtained directly; values obtained from measurements are not treated as errorless; and it yields a single residual term that can be used for statistical comparison among binding models and/or experiments. We have compared this approach with the common practice of analyzing the association and dissociation phases separately, either by nonlinear regression or by linear regression after suitable transformations. With respect to both the precision and accuracy of parameter estimates, the simultaneous procedure was superior to the other two methods. The properties of the simultaneous procedure were further investigated, concerning both parameter estimation and the probability of reliably detecting a second binding site. For the latter, the relative density of receptor subtypes and the dissociation rate constants were found to be of major importance, whereas association rate constants and ligand concentration were of minor importance in this respect. The probability of resolving two sites by kinetic or equilibrium data under similar conditions with the aid of a single labeled ligand was examined. When the selectivity of the ligand was low, the resolution was found to be more probable when based on kinetic, rather than equilibrium, data. This was true at higher selectivities as well, provided kinetic data were obtained at two different ligand concentrations. PMID- 2913483 TI - Secobarbital-mediated inactivation of rat liver cytochrome P-450b: a mechanistic reappraisal. AB - Administration of the allylbarbiturate secobarbital (SB) to phenobarbital pretreated rats is known to result in structural and functional loss of hepatic cytochrome P-450 and generation of N-alkylated prosthetic heme derivatives. Isozyme-selective functional markers have led us to confirm P-450b as the isozyme selectively inactivated by the drug. In contrast to its inactivation by allylisopropylacetamide, such SB-inactivated P-450b is not amenable to structural and functional repair by exogenous heme, for reasons that remain unclear. In an effort to gain some insight, we have explored various possible mechanisms. In the course of these studies with rat liver microsomes enriched in P-450b as well as isolated purified P-450b, we have found that, along with prosthetic heme alkylation, a significant fraction of the hemoprotein also undergoes drug mediated alkylation of the apocytochrome, presumably at the active site. Accordingly, an equimolar ratio of irreversibly bound drug to functionally inactive residual P-450b chromophore is observed after incubation of the purified isozyme with SB and NADPH. Thus, P-450b-mediated oxidative metabolism of SB appears to partition not only between prosthetic heme alkylation and epoxidation but apoprotein alkylation as well. PMID- 2913485 TI - Tacrine protection of acetylcholinesterase from inactivation by diisopropylfluorophosphate: a circular dichroism study. AB - Tacrine (1,2,3,4-tetrahydro-9-aminoacridine) showed an apparent noncompetitive inhibition of Torpedo acetylcholinesterase (AChE) with a dissociation constant, Ki, of 8.5 nM. It altered the CD bands of AChE in the near-UV region, which monitor the local conformation of aromatic side groups, but not those in the far UV region, which measure the secondary structure. An extrinsic CD band was induced at 348 nm, with a molar ellipticity of 35,000 deg cm2 dmol-1 (bases on tacrine), when each AChE subunit (Mr = 67,000) was saturated with one tacrine (mol/mol). With this band as a probe, the bound tacrine could be displaced by edrophonium or decamethonium, both of which are known to bind to the anionic site at the active center of AChE, but not by propidium, which binds to the peripheral site of the enzyme. Tacrine protected AChE from inactivation by diisopropylfluorophosphate (DFP). AChE completely lost its enzymatic activity when 1 mol of DFP was bound per mol of subunit upon incubation of 7 microM AChE (subunit) with 100 microM DFP for 40 min, but tacrine-treated AChE retained 60% of its activity and bound only 0.2 mol of DFP per mol of subunit under similar conditions. The corresponding CD, at 348 nm, of the AChE-tacrine-DFP complex increased or decreased gradually, depending on the order of addition of tacrine and DFP, and reached an equilibrium value (80% of its original) after 2 days. The difference absorption spectrum of the AChE-tacrine-DFP complex was the same as that of the AChE-tacrine complex. These results suggest that the protective effect of tacrine may be due to steric hindrance at the esteratic site of the enzyme. PMID- 2913486 TI - Conformational and steric aspects of phenylethanolamine and phenylethylamine analogues as substrates or inhibitors of phenylethanolamine N-methyltransferase. AB - The conformational and steric aspects of binding to phenylethanolamine N methyltransferase (PNMT; EC 2.1.1.28) for phenylethanolamine substrates and phenylethylamine inhibitors were probed with three conformationally defined analogues (11, 12, and 13) of phenylethylamine (1) and phenylethanolamine (6) containing the benzobicyclo[3.2.1]octane skeleton. The 2-aminotetralin (2AT) moiety in conformationally defined analogues 11, 12, and 13 exists in a half chair conformation with an equatorial amino group. Although conformationally restricted phenylethylamine analogue 2AT (3, Ki = 6.8 microM) and conformationally restricted phenylethanolamine analogues (cis)- and (trans)-2 amino-1-tetralol (9, Km = 22 microM; Vmax = 0.15; 100 X Vmax/Km = 0.68; 10, Ki = 9.4 microM) are good ligands for PNMT, none of the analogues 11, 12, and 13 showed activity as a substrate of PNMT. The fact that 11 (Ki = 206 microM) is more potent than analogues 4 (Ki = 1296 microM) and 5 (Ki = 479 microM), with a half-boat 2AT moiety, suggests that PNMT preferentially binds the half-chair conformation of 2AT at the active site. This is consistent with previous findings that a fully extended conformation for the aminoethyl side chain of phenylethylamine inhibitors is optimal for PNMT binding. The reduced activity of 11, 12 (Ki = 1246 microM), and 13 (Ki = 3000 microM), compared with 2AT and (cis) and (trans)-2-amino-1-tetralol (9 and 10) is consistent with a negative steric interference from the extra ethano bridge in 11, 12, and 13. The results from 11, 12, and 13, combined with previous findings, suggest that PNMT interacts better with relatively planar ligands. PMID- 2913487 TI - Chromosomal aberrations and sister-chromatid exchanges in tool and die workers. AB - Because tool and die workers are exposed to a number of potentially genotoxic agents, including mutagenic metals, polyaromatic hydrocarbons, and nitrosamines, and may be at increased cancer risk, the present study was undertaken to test whether chromosomal damage in peripheral blood cells is associated with work in the tool and die industry. Lymphocyte cultures were established from 27 tool and die fabrication workers from one manufacturing plant who had worked in the trade for more than 15 years. 15 of these workers also had some form of malignancy at the time of the study, but had not been treated with radiation or chemotherapies that could themselves induce chromosomal damage. The frequencies of chromosomal aberrations and sister-chromatid exchanges (SCEs) were measured in workers and the data compared with those of a control group consisting of 7 non-fabrication workers from the same plant and 8 age-matched community controls. In addition, the relative rates of lymphocyte proliferation were estimated for each group by analyzing the percentages of first-, second- and third-division mitotic cells after 72 h of culture. The results of the chromosomal studies show that tool and die workers have significantly increased frequencies of aberrations whether engaged in fabrication work or not, compared to control subjects. The frequency of SCEs and the frequencies of 1st, 2nd and 3rd division figures are not different among the study groups. Among workers who are engaged in fabrication, including those who are cancer patients, the frequency of more complex aberrations (i.e., interstitial deletions and small acentric fragments) is increased. In a five-year follow-up of these workers, 2 of the 13 workers with these aberrations developed some form of colon cancer. Whether the presence of interstitial deletions and small acentric fragments is related to the occupation of these workers, or is tangentially related to the development of cancer, is presently under consideration. PMID- 2913488 TI - Cytotoxic and genotoxic effects of extracellular generated singlet oxygen in human lymphocytes in vitro. AB - The induction of sister-chromatid exchanges (SCE) together with the proliferation rate index (PRI) were studied in human lymphocytes in vitro after treatment with singlet oxygen. When produced outside the cells, singlet oxygen can increase the duration of the cellular cycle as measured by an enhancement of the differences between the proliferation rate indexes of the control and the treated cells. A dose-dependent increase in the SCE rate per chromosome was also detected after contact between the singlet oxygen and lymphocytes. PMID- 2913489 TI - Comparative study of sister-chromatid exchanges and chromosomal aberrations induced by airborne particulates from an urban and a highly industrialized location in human lymphocyte cultures. AB - Cytogenetic effects induced by extracts of airborne particulates in human lymphocyte cultures were studied with regard to local and seasonal variations. Samples of airborne particulates were collected from an urban and a highly industrialized area in March and October, respectively. All extracts of particulates induced a significant increase of sister-chromatid exchanges (SCE) in a dose-dependent manner. Referring to the induction of sister-chromatid exchanges, local and seasonal differences were observed. Samples from the industrialized area revealed the highest activities. In addition, SCE rates found for March samples were always higher than those for October for both locations. Furthermore, a remarkable, significant induction of chromosomal aberrations occurred with all samples from both locations and sampling periods. Aspects of health risk evaluation for exposed human populations are discussed with respect to the observed cytogenetic effects of airborne particulates in human lymphocyte cultures. PMID- 2913490 TI - An adaptive response of Vibrio cholerae strain OGAWA 154 to furazolidone. AB - Since furazolidone is an antimicrobial drug, any possibility of its evoking an adaptive response appears to be very important. This response was studied in Vibrio cholerae cells as a model system. In order to determine this response, a dose-response relation of these cells to furazolidone and the kinetics of inactivation of the drug were studied. The study of the adaptive response of these cells to furazolidone reveals that cells treated with a low concentration of furazolidone for a particular period were 100% more resistant to the lethal effects of a subsequent challenging dose than control cultures. Variation of the challenging dose level showed better survival of adapted cells than control cells. A time-dependent response study reveals a maximum response at 15-30 min, and a gradual fall thereafter. PMID- 2913491 TI - Effects of pH in the in vitro chromosomal aberration test. AB - The relation between the pH of the medium and clastogenic activity was studied in Chinese hamster ovary (CHO) K1 cells in vitro. The pH was adjusted with NaOH, KOH, HCl or H2SO4. No clastogenic activity was observed over the initial pH range of 7.3-10.9 without S9 mix, but a few chromosomal aberrations were induced at pH 10.4 with S9 mix. The frequency of aberrations increased with the increase in amount of S9. At acidic pH, many chromatid breaks were induced at initiatial pH 5.5 or below without S9 mix, and aberrations such as chromatid breaks and chromatid exchanges were induced at initial pH 6.2 or below with S9 mix. Using MES and Bis-Tris as buffers instead of sodium bicarbonate, we observed that aberrations of the chromatid break type were inducible at pH 6.2 or below. These results show that the combination of strong alkalinity and S9 is clastogenic to CHO-K1 cells, and also that weakly acidic media are genetically active. The results indicate that incubations at non-physiological pH might give false positive responses. PMID- 2913492 TI - Provocation of bradycardia and hypotension by isoproterenol and upright posture in patients with unexplained syncope. AB - Neurally mediated hypotension and bradycardia are believed to be common causes of syncope. We used the "upright-tilt test" (duration, less than or equal to 10 minutes) with or without an infusion of exogenous catecholamine (isoproterenol [1 to 5 micrograms per minute], given intravenously) to elicit bradycardia, hypotension, or both in 24 patients with recurrent syncope and in 18 control subjects. A conventional electrophysiologic test performed before the tilt test was positive in 9 of the 24 patients, revealing arrhythmias that may have caused recurrent syncope, but was negative and thus nondiagnostic in 15 patients. The tilt test alone (i.e., without isoproterenol) induced symptomatic bradycardia or hypotension in 1 of the 9 patients with positive electrophysiologic tests (11 percent), 4 of the 15 patients with negative electrophysiologic tests (27 percent), and none of the controls. When the isoproterenol infusion was administered during the tilt test, 9 of the 11 patients with negative electrophysiologic and tilt tests had syncope, marked slowing of the heart rate, and hypotension. In contrast, isoproterenol was associated with tachycardia and only a slight decline in arterial pressure in the 8 remaining patients with positive electrophysiologic tests and the 18 control subjects, and syncope developed in only 1 of the 8 patients with positive electrophysiologic tests and negative tilt tests (13 percent) and 2 of the 18 control subjects (11 percent). We conclude that an isoproterenol infusion administered in conjunction with the upright-tilt test may be useful for identifying susceptibility to neurally mediated recurrent syncope. PMID- 2913493 TI - Comparative effectiveness and costs of inpatient and outpatient detoxification of patients with mild-to-moderate alcohol withdrawal syndrome. AB - We compared the effectiveness, safety, and costs of outpatient (n = 87) and inpatient (n = 77) detoxification from alcohol in a randomized, prospective trial involving 164 male veterans of low socioeconomic status. The outpatients were evaluated medically and psychiatrically and then were prescribed decreasing doses of oxazepam on the basis of daily clinic visits. The inpatient program combined comprehensive psychiatric and medical evaluation, detoxification with oxazepam, and the initiation of rehabilitation treatment. The mean duration of treatment was significantly shorter for outpatients (6.5 days) than for inpatients (9.2 days). On the other hand, significantly more inpatients (95 percent) than outpatient (72 percent) completed detoxification. There were no serious medical complications in either group. Outcome evaluations completed at one and six months for 93 and 85 percent of the patients, respectively, showed substantial improvement in both groups at both follow-up periods. At one month there were fewer alcohol-related problems among inpatients and fewer medical problems among outpatients. However, no group differences were found at the six-month follow-up, nor were differences found in the subsequent use of other alcoholism-treatment services. Costs were substantially greater for inpatients ($3,319 to $3,665 per patient) than for outpatients ($175 to $388). We conclude that outpatient medical detoxification is an effective, safe, and low-cost treatment for patients with mid-to-moderate symptoms of alcohol withdrawal. PMID- 2913495 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 6-1989. A 57-year-old man with increasing dyspnea and a mediastinal mass. PMID- 2913494 TI - A child with phenotypic Laron dwarfism and normal somatomedin levels. PMID- 2913496 TI - Ventricular syncope: is the heart a sensory organ? PMID- 2913497 TI - Left ventricular thrombi and cerebral embolism. PMID- 2913499 TI - Practicing intubation of the newly dead. PMID- 2913498 TI - Treatment of alcoholism. PMID- 2913500 TI - Prerenal failure. PMID- 2913501 TI - Gamma globulin deficiency in newborns with congenital nephrotic syndrome. PMID- 2913502 TI - Case 28-1988. PMID- 2913503 TI - Case 35-1988. PMID- 2913504 TI - Disinfecting barbers' instruments. PMID- 2913505 TI - Holiday heart type II. PMID- 2913506 TI - The effects of alcoholism on skeletal and cardiac muscle. AB - To determine the prevalence of alcoholic myopathy and cardiomyopathy, we studied a group of 50 asymptomatic alcoholic men (mean age, 38.5 years) entering an outpatient treatment program. Studies performed included an assessment of muscle strength by electronic myometer, muscle biopsy, echocardiography, and radionuclide cardiac scanning, with comparison to healthy control subjects of similar age. The patients' mean (+/- SEM) daily alcohol consumption was 243 +/- 13 g over an average of 16 years. These patients had no clinical or laboratory signs of malnutrition or electrolyte imbalance. Forty-two percent of the patients, as compared with none of the controls, had strength of less than 20 kg as measured in the deltoid muscle. Muscle-biopsy specimens from 23 patients (46 percent) had histologic evidence of myopathy. In the cardiac studies, when the alcoholic patients were compared with 20 healthy controls, the patients had a significantly lower mean ejection fraction (59 vs. 67 percent), a lower mean shortening fraction (33 vs. 38 percent), a greater mean end-diastolic diameter (51 vs. 49 mm), and a greater mean left ventricular mass (123 vs. 106 g per square meter of body-surface area). One third of the alcoholics had an ejection fraction of 55 percent or less, as compared with none of the controls. Endomyocardial biopsy specimens from six patients with ejection fractions below 50 percent showed histologic changes of cardiomyopathy. The estimated total lifetime dose of ethanol correlated inversely with muscular strength (r = -0.65; P less than 0.001). In an analysis that also included six patients with symptomatic alcoholic cardiomyopathy, the estimated total lifetime dose of ethanol correlated inversely with the ejection fraction (r = -0.58; P less than 0.001) and directly with the left ventricular mass (r = 0.59; P less than 0.001). We conclude that myopathy of skeletal muscle and cardiomyopathy are common among persons with chronic alcoholism and that alcohol is toxic to striated muscle in a dose-dependent manner. PMID- 2913507 TI - Treatment of children with port-wine stains using the flashlamp-pulsed tunable dye laser. AB - Thirty-five children, three months to 14 years of age, with disfiguring port-wine stains were treated with a flashlamp-pulsed tunable dye laser. All had complete clearing of the stains after an average of 6.5 laser treatments to each lesional area; skin over bony prominences required approximately half as many sessions as skin on the cheek. Children less than seven years old required fewer sessions (mean +/- SD, 5.8 +/- 1.1) than older children (7.1 +/- 1.1; P less than 0.05). Treated skin was identical in texture and color to adjacent normal skin in 33 (94.3 percent) of the children, whereas 2 (5.7 percent) had small, isolated, depressed scars in areas accidentally traumatized soon after laser treatment. The only other side effect was transient hyperpigmentation, which occurred in 20 patients (57 percent). These results can be attributed to two distinguishing characteristics of the flashlamp-pulsed tunable dye laser: an emission wavelength of 577 nm, theoretically ideal for selective absorption by the intravascular target oxyhemoglobin, and a pulse duration of 360 microseconds, which closely matches the thermal relaxation time for dermal blood vessels and hence avoids diffuse nonspecific thermal necrosis with subsequent scarring of the treated skin. PMID- 2913508 TI - Closed-chest ablation of retrograde conduction in patients with atrioventricular nodal reentrant tachycardia. AB - We applied a new technique of catheter ablation to treat atrioventricular nodal reentrant tachycardia and preserve anterograde conduction, performing this procedure in 21 patients with repetitive episodes of tachycardia refractory to antiarrhythmic drugs. Using atrial activation in the His-bundle lead as a reference, we selected the optimal site of ablation by positioning an electrode catheter so that atrial activation occurred simultaneously with or earlier than the reference activation during tachycardia. At this site, the His-bundle deflection was completely absent or was present only at a low amplitude (less than 0.1 mV). In the majority of patients, these criteria could be met by withdrawing the catheter 5 to 10 mm from the site of the His-bundle recording (adjacent to the reference catheter). Shocks of 160 or 240 J were delivered at this site (cumulative energy [mean +/- SD], 689 +/- 442 J). Treatment resulted in preferential abolition or impairment of retrograde nodal conduction. Anterograde conduction, although modified, was preserved in 19 patients; complete heart block persisted in 2 patients. Sixteen patients remained free of arrhythmia, without medication or implantation of a pacemaker, for a mean follow-up period of 14 +/- 8 months (range, 7 to 42). Tachycardia was not inducible in 14 patients in a follow-up electrophysiologic study performed 3.6 +/- 6 months after the procedure. We conclude that catheter ablation is an effective alternative for the treatment of atrioventricular nodal tachycardia in patients with drug-resistant tachycardia. PMID- 2913510 TI - Alcoholic myopathy and cardiomyopathy. PMID- 2913509 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 7-1989. Unilateral exophthalmos three years after treatment of cervical and mediastinal Hodgkin's disease. PMID- 2913511 TI - Catheter techniques for ablation of supraventricular tachycardia. PMID- 2913512 TI - Screening for human immunodeficiency virus infections. PMID- 2913513 TI - More on transmission of HIV by blood transfusion. PMID- 2913515 TI - Emotional distress during magnetic resonance imaging. PMID- 2913514 TI - Dexamethasone therapy for bacterial meningitis. PMID- 2913516 TI - In defence of the psyche. PMID- 2913517 TI - General practitioners' attitudes to advertising and competition. PMID- 2913518 TI - Medicine in rural Kenya: a personal perspective. PMID- 2913519 TI - Health care and education. PMID- 2913520 TI - Health promotion and wellness. PMID- 2913522 TI - A standard for ethical committees. PMID- 2913521 TI - Myalgic encephalomyelitis. PMID- 2913523 TI - Information and consent. PMID- 2913524 TI - The Mason report. PMID- 2913525 TI - Alternative medicine. PMID- 2913526 TI - Sudden infant death. PMID- 2913527 TI - The scientific method. PMID- 2913528 TI - Smoking and financial health. PMID- 2913529 TI - Autopsy and the cause of death. PMID- 2913531 TI - The indications for abortion. PMID- 2913530 TI - The fate of cervical smears with minimal abnormality. PMID- 2913532 TI - Prescription charges. PMID- 2913533 TI - Bed availability as a significant influence on rates of committal to New Zealand's psychiatric hospitals. AB - Analysis of the data on committal to psychiatric institutions shows that there is a wide variation in risk of committal between hospital board areas and that this risk is strongly related to the availability of psychiatric institutional beds. The risk of remaining in an institution as a committed patient is even more strongly related to bed availability. These findings, which suggest that committal may be less related to objective clinical criteria than to other external factors, are of concern in view of the revision to compulsory treatment procedures currently before Parliament. PMID- 2913534 TI - A presidential message. PMID- 2913535 TI - A survey of drug prescribing practices of dentists. AB - A survey of drug prescribing habits of 357 dentists practicing in five counties in Western New York was conducted in 1986. Respondents represented both general practitioners and specialists who were graduates of 25 different dental schools. From this study it can be concluded that dentists prescribe a wide range of drugs representing over 13 drug categories. The most frequently prescribed drug categories were antibiotics, narcotic analgesics, non-steroidal inflammatory agents, non-narcotic analgesics, and fluorides. The most frequent prescribers of drugs were oral surgeons, endodontists and periodontists. PMID- 2913536 TI - A new material and technique for appliance therapy. AB - A new material (thermoplastic) and clinical technique has been presented which can be utilized for appliance therapy. The major occlusal problems caused by distortion of acrylic appliances after traditional heat curing has been eliminated by this material. As a result, a clinical technique has been suggested that utilizes a relieved duplicate master cast that is mounted on the articulator for wax up and processing purposes. The inordinate accuracy of the material permits the finished appliance to be reseated on the master cast with great precision. The occlusion is refined and the appliance inserted with insignificant occlusal adjustment. PMID- 2913537 TI - Third party audit of dental records. PMID- 2913538 TI - A modified bruxism appliance. PMID- 2913539 TI - On infection control. PMID- 2913540 TI - Extraction of third molars. PMID- 2913541 TI - [Malignant arrhythmia]. AB - About 5 percent of the arrhythmias are serious, life threatening, malignant arrhythmias (MA). The MA is regularly associated with organic heart diseases (coronary heart disease, cardiomyopathy, valvular heart diseases), but a MA can develop without cardiac disorders e.g. in long QT syndrome or WPW syndrome. The most frequent type of the MA is the ventricular tachycardia (VT), mostly the sustained VT, not rarely degenerating to ventricular fibrillation (VF). The primary VF represents a rarer form of MA. The usual type of MA is the tachycardiac form, but there exists a MA with dominating bradycardia (bradycardia syncope, tachycardia associated with long lasting bradycardia). In the diagnosis of MA new investigatory methods (signal averaged electrography with high amplification, Holter monitoring, programmed electrical stimulation) play an important role. In the therapy of the MA the first step is the treatment of the cardiac disease involved in the pathogenesis of the MA. At present only about the 40% of the MA can be effectively treated with antiarrhythmic drugs. The pacemaker therapy is very efficacious in the bradycardiac type of MA. Cardiodefibrillator pacemaker can be used for the treatment of grave VT or VF. Electrical transvenous catheter ablation, heart surgical intervention can also be applied in the treatment of special MA. The prognosis of VA was very serious a decade ago, now with application of newer therapeutical procedure the prognosis of MA is permanently improving. PMID- 2913542 TI - [Management of thermal injuries]. PMID- 2913543 TI - Selected topics in pediatric pathology. PMID- 2913544 TI - The value of the pediatric postmortem examination. AB - Requesting an autopsy is never a pleasant or comfortable experience, either for physician or for family members. Sometimes the family has had previous unhappy experiences with this procedure, and certainly many clinicians have been repelled by sights, sounds, and behaviors they have observed in morgues. Such experiences can have far-reaching negative effects and reflect poorly upon the profession of pathology. Berger's important paper contains important messages for pathologists concerned with the performance of pediatric autopsies and for clinicians requesting consent. His paper should be read and heeded by both groups. Several studies have looked at factors that might affect autopsy rates, especially in perinatal deaths. Early separation of mother from baby emerged as an important factor in one of these, whereas maternal age, race, and sociocultural background played no important role. One of these studies investigated attitudes and experiences of the requesting physicians, and found these factors to be key determinants in the family's response to a request to perform a postmortem examination. One result of that study was that more experienced physicians were more likely to request a postmortem examination, and to receive an affirmative answer. The pediatric postmortem examination remains an indispensable part of clinical management. Its importance for science, clinical practice, and medical administration is beyond question. However, its greatest and most unique value is to the families of the deceased children. Clinicians and pathologists must continue to work together to ensure that this procedure is performed whenever indicated, that the information gained is maximized, and that the results are communicated to the family promptly, accurately, clearly, and with sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2913545 TI - Pediatric specimen collection for chemical analysis. AB - Laboratory tests can be an important factor in patient care and health care costs. To maximize their utility and cost effectiveness, one must be aware of factors that can compromise their accuracy. The process from choice of tests to interpretation of results is complex, but it can be successfully completed if the variables discussed in this article are minimized. Note: Since submission of this manuscript, an article summarizing the neonatal experience at Columbus Children's Hospital and several surveyed pediatric hospitals has been published. This article reviews methods and provides numerous suggestions on improving technique. PMID- 2913546 TI - Laboratory detection of metabolic disease. AB - This article describes the clinical signs, abnormal chemistry, histopathology, and biochemical tests that assist in the diagnosis of many inherited metabolic diseases. Small molecule diseases (for example, amino acid disorders, organic acidurias, and galactosemia) may present with acute illness and lead to unexplained death. Diagnosis of the specific enzyme defect may permit treatment by dietary changes or vitamin supplementation. Large molecule diseases are degenerative disorders due to storage of glycogen, glycoproteins, or mucopolysaccharides. Table 7 presents a compendium of laboratory investigations one should consider using when abnormalities are found in multiple organ systems. The investigation of a child with a mucopolysaccharidosis is used as an example of the use of this table. Investigating pediatricians should realize that many laboratory tests involved in the diagnosis of metabolic disease required special collection and handling by the laboratory. PMID- 2913547 TI - Delayed cerebrospinal fluid sterilization and adverse outcome of bacterial meningitis in infants and children. AB - To determine the clinical importance of CSF cultures that are persistently positive for pathogens in patients treated for meningitis with the new cephalosporins, the records of 301 infants and children with bacterial meningitis enrolled prospectively in four clinical efficacy trials of cefuroxime or ceftriaxone therapy were reviewed. CSF culture results were positive for 20 patients and they were sterile at 18 to 36 hours after start of therapy for 281 patients. Seizures, subdural effusions, and hemiparesis were found significantly more often during hospitalization in those with delayed sterilization of CSF. Children with persistently positive cultures had a significantly higher incidence of neurologic abnormalities at the time of hospital discharge (45% v 19%) and at follow-up (41% v 13%) and of moderate to profound hearing impairment (35% v 15%) than did those with prompt sterilization of CSF. Repeat CSF examination is a useful prognostic indicator in infants and young children with bacterial meningitis. PMID- 2913548 TI - Socioeconomic differentials and neonatal mortality: racial comparison of California singletons. AB - The median family income of the zip code of maternal residence was used to estimate the presence and determine the extent of socioeconomic differentials in the neonatal mortality rates of a cohort of 401,399 white and of 66,577 black Californian singletons born from 1982 to 1983. The neonatal mortality rate in the white infants increased from 3.99 in mothers residing in zip codes with a median family income greater than $25,000 to 12.1 for mothers residing in zip codes with a median family income less than $11,000. With decreasing socioeconomic status there was also a significant increase in the percentage of white infants weighing less than 2,500 g (percentage of low birth weight increased from 3.75 to 8.33) and weighing less than 1,500 g (percentage of very low birth weight increased from 0.56 to 1.46). When the source of the socioeconomic difference in white neonatal mortality was partitioned, 77.4% was due to deterioration in the birth weight distribution and 22.6% to deterioration in the birth weight-specific mortality rates. For the black cohort, the neonatal mortality rate increased from 5.9 in the most, to 9.0 in the least affluent strata. Although decreasing residential median family income was associated with an increase in the percent low birth weight (8.19 v 12.86), the percentage of very low birth weight was not significantly different (1.59 v 2.10). When the source of the differential in black neonatal mortality was partitioned, only 29% was due to deterioration of the birth weight distribution, whereas 71% was secondary to less favorable birth weight-specific mortality rates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2913549 TI - Cognitive and motor differences among low birth weight infants: impact of intraventricular hemorrhage, medical risk, and social class. AB - The independent impacts of severe intraventricular hemorrhage, other common medical complications of prematurity, and socioeconomic status on the development in the second year of life of 32 low birth weight subjects were explored. Outcome measures included standard tests of mental and motor development, an evaluation of language competence, and an assessment of information processing ability in a habituation/recovery paradigm. Partial correlations indicated that intraventricular hemorrhage influences cognitive and motor development independently of the other predictor variables. Socioeconomic status predicted language ability and recovery of attention to a novel stimulus independent of the other predictors. Medical complications other than intraventricular hemorrhage also made an independent contribution to the variance in language outcome. Implications of these findings are discussed. PMID- 2913550 TI - Hospital-acquired urinary tract infection. AB - From 16,534 admissions, 60 patients, 4 days to 15 years of age, with one or more hospital-acquired urinary tract infections were identified during a 5-year period by a prospective surveillance system. The patient charts were subsequently reviewed to characterize the population at risk for such infections and to describe the course and consequences of these infections. Infections in individual patients ranged from one to greater than 50. The hospital-acquired urinary tract infection rate for the study period was 14.2 infections per 1,000 admissions. In the patients in whom all urinary tract infections were well documented, the following characteristics were defined: (1) 92% (97 of 105) of the infections occurred in catheterized patients; (2) almost half (49 of 105) of the infections occurred in patients exposed to only intermittent catheterization; (3) 28% (29 of 105) of the infections were asymptomatic; (4) fever was the most frequent finding in the symptomatic patients and occurred in 66% (60 of 105); (5) pyuria was found in only 51% (35 of 69) of the urinalyses performed at diagnosis; (6) 85% (89 of 105) of the infections were single-organism infections; (7) 82% (101 of 123) of the causative organisms were Escherichia coli, Pseudomonas sp, coagulase-negative staphylococci, Enterococcus spp, Klebsiella spp, or Enterobacter sp. The urinary tract infections in the 60 patients were not complicated by bacteremia, and no direct relationship between the infections and the minimal mortality in our patients could be established. PMID- 2913551 TI - Self-esteem in children medically managed for attention deficit disorder. AB - Self-esteem was measured initially in a group of 21 eight- to 12-year-old children with newly diagnosed attention deficit disorder/hyperactivity and remeasured after 1-month courses of treatment with methylphenidate and placebo given in double-blind crossover fashion. Multimodal management of all patients included diagnosis, demystification, medication, close follow-up with supportive counseling, and referral as indicated for psychosocial and educational assistance. Long-term follow-up of 12 children who continued to receive methylphenidate was done for an average of 16 months. Initial total self-esteem was low in 30% of all subjects, intermediate in 55%, and high in 15%. No statistically significant changes occurred in self-esteem during the short-term phase of the study despite clinically significant behavioral responses to medication as assessed by serial questionnaires. At long-term follow-up, total, general, and academic self-esteem scores were improved significantly, however. These findings indicate that many preadolescents with attention deficit disorder/hyperactivity exhibit low self-esteem. Despite clinical response to medication, short-term improvement in self-esteem may not occur; however, long term, multimodal management that includes medication does appear to improve self esteem. PMID- 2913552 TI - Language growth in children with expressive language delay. AB - Developmental expressive language disorder is a frequently occurring condition in children, characterized by severe delay in the development of expressive language compared with receptive language and cognitive skills. Opinions differ regarding whether expressive language delay is a disorder worthy of active intervention or an indication of normal variation in the onset of expressive language. The purpose of this research was to follow for 5 months 26 2-year-old children in whom expressive language disorder had been carefully diagnosed to discover the rate of improvement and its predictors. Improvement was variable, with approximately one third of the children showing no improvement, one third showing mild improvement, and one third in the normal range at posttest. Nearly two thirds of the variance in improvement could be accounted for by three child variables measured by the pretest: parentally reported vocabulary size, parentally reported problems with having regular meals, and observed frequency of quiet activity not requiring the parent's management. A screening procedure involving only one of those variables, reported vocabulary size, was 81% accurate in identifying children's improvement status. The implications of these results for the management of children with expressive language disorder are discussed. PMID- 2913553 TI - Systemic lupus erythematosus in the first decade of life. AB - To evaluate whether the onset of systemic lupus erythematosus in the first decade of life was associated with a unique pattern of racial preponderance, sexual preponderance, genetic predisposition, or disease expression, the medical records of 23 children with systemic lupus erythematosus prior to their tenth birthdays were compared with the medical records of 82 children in whom lupus was diagnosed between their tenth and 20th birthdays. No statistically significant differences in sex distribution, racial (ethnic) background, family history, mode of onset, morbidity, or mortality rates were found between the two age groups. The frequently held view that children with early-onset lupus do worse probably relates to the fact that even though they survive as long as children with the older-onset disease, they die younger because they have the onset of their lupus at a younger age. PMID- 2913554 TI - Normative arm and calf blood pressure values in the newborn. AB - Indirect BP measurement was obtained in the right upper arm in 219 healthy newborn infants with the Dinamap monitor and was compared with values obtained from the calf to establish normative BP values and to help establish a diagnosis of hypertension and coarctation of the aorta in the newborn. There were 174 Mexican-Americans (79.5%), 33 whites (15.0%), and 12 blacks (5.5%). The width of the BP cuff was selected to be 0.4 to 0.5 times the circumference of the extremities. Three supine position readings of BPs and heart rate were obtained from each site and were averaged for statistical analyses. Mean arm BP values (+/ SD) of the neonate less than 36 hours of age were 62.6 +/- 6.9/38.9 +/- 5.7 mm Hg (48.0 +/- 6.2 mm Hg). Neonates older than 36 hours had slightly but significantly (P less than .05) greater values (4 to 6 mm Hg) than did infants younger than 36 hours of age. Active neonates had values 6 to 10 mm Hg greater than quiet neonates (P less than .05). BP values in the calf obtained with the same-sized cuff were almost identical with those obtained from the arm. Differences in consecutively obtained arm and calf BPs (arm values minus calf values) were 1.1 +/- 7.7 mm Hg systolic, -0.01 +/- 6.2 mm Hg diastolic, and 0.9 +/- 6.9 mm Hg mean pressures. Mean heart rate (+/- SD) of neonates less than 36 hours of age was 129.4 +/- 13.2 beats per minute and that of neonates older than 36 hours of age was 139.4 +/- 14.1 beats per minute.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2913555 TI - Nocturnal hypoventilation in children with nonprogressive neuromuscular disease. AB - Eight patients between 4 and 24 years of age with nonprogressive neuromuscular disease sought medical attention because of severe nocturnal hypoventilation. There were two types of findings: subacute with progressive early morning headaches and daytime drowsiness and acute with ventilatory failure and cor pulmonale. Seven patients were ambulant. Seven were successfully treated with either a cuirass negative pressure ventilator or a positive pressure ventilator via a tracheostomy. The ventilatory assistance was only used at night and resulted in rapid resolution of early morning symptoms and a return to full daytime activity. One patient died as a result of an intercurrent respiratory infection before respiratory support could be given. It is important to be aware of this potentially life-threatening complication in patients with an otherwise good prognosis and of the benefit to be derived from active treatment. PMID- 2913556 TI - Cow's milk whey protein elicits symptoms of infantile colic in colicky formula fed infants: a double-blind crossover study. AB - There are several causes of infantile colic. The aim of this study was to evaluate, under controlled conditions, whether bovine whey proteins can elicit symptoms of infantile colic in colicky formula-fed infants. The mean age for entering the study was 6.4 weeks and the mean age for colic debut was 3.7 weeks. In 24 of 27 infants with severe colic, the symptoms disappeared when they were given a cow's milk-free diet (Nutramigen). These 24 infants were entered into a double-blind crossover study. The infants (receiving cow's milk-free diet) were given the contents of identical capsules with each meal during day 6. The same procedure was repeated on day 10. The capsules contained either whey protein powder (with Nutramigen added) or human albumin powder (with Nutramigen added). Eighteen infants receiving the whey protein-containing capsules reacted with colic, two infants receiving placebo reacted with colic (P less than .001), and four infants did not react at all. Crying hours per day for the 24 infants were 5.6 hours for formula-fed infants and 0.7 hour for cow's milk-free diet-fed infants (P less than .001). Crying hours per day were 3.2 hours for the infants receiving whey protein capsules and 1.0 hour for those receiving placebo (P less than .001). In conclusion, bovine whey protein can elicit symptoms of infantile colic in colicky formula-fed infants. PMID- 2913557 TI - Fatal farm injuries among young children. AB - Death certificate data concerning farm-related injury deaths among children 0 to 9 years of age in Wisconsin and Illinois for the period of 1979 to 1985 were reviewed. Average annual farm-related injury death rates were 3.2 per 100,000 rural children in Wisconsin (62 deaths) and 1.5 per 100,000 in Illinois (32 deaths). Rates were three times higher among boys than girls. The occurrence of two harvest-related peaks and the absence of fatality in children less than 1 year of age suggest that presence of children on the farm when supervision is diminished is a key factor in farm-related fatalities. Moving machinery (tractors, wagons, and trucks) was the source of injury in approximately 55% of all deaths. Drowning accounted for 15% of all farm-related deaths. Two fatalities related to gravity box wagons could have easily been prevented with simple safety devices. These findings suggest a need for developing environmental interventions in farms. This will require the allocation of more resources to farm safety programs and a revision of current farm safety legislation. PMID- 2913558 TI - Psychologic morbidity of children subjected to Munchausen syndrome by proxy. AB - Munchausen syndrome by proxy is being recognized and reported with increasing frequency, which suggests that it is more common and occurs with a wider spectrum of severity than was previously suspected. In past reports, the difficulties of detecting and documenting the syndrome have been emphasized, as well as its physical morbidity and mortality. The psychologic morbidity of Munchausen syndrome by proxy in six children is described. The children reacted with developmentally appropriate behavior problems ranging from feeding disorders in infants, withdrawal and hyperactivity in preschool-aged children, to hysterical disorders and personal adoption of Munchausen syndrome behavior in adolescents. Parental psychologic and behavioral styles, family dynamics, and responses from legal and children's protective services systems make protection of the child within the home difficult, if not impossible. Even with protection from further physical injury, severe psychologic trauma remains likely. Extreme caution is suggested in allowing these children to remain in the family. PMID- 2913559 TI - Ethical issues in preventive pediatrics. PMID- 2913560 TI - American Academy of Pediatrics Committee on Medical Liability: Professional liability coverage for residents. PMID- 2913561 TI - American Academy of Pediatrics Committee of Medical Liability: Guidelines for expert witness testimony. PMID- 2913562 TI - American Academy of Pediatrics Committee on Communications: Impact of rock lyrics and music videos on children and youth. PMID- 2913563 TI - Syllabic pitch perception in 2- to 3-month-old infants. AB - The pitch patterns present in speech addressed to infants may play an important role in perceptual processing by infants. In this study, the high-amplitude sucking procedure was used to assess discrimination by 2- to 3-month-old infants of rising versus falling pitch patterns in 400-msec synthetic [ra] and [la] tokens. The syllables' intonation contour was modeled on infant-directed speech, and covered a range characteristic of an adult female speaker (180-300 Hz). Group data indicated that the 2- to 3-month-old infants discriminated the pitch contour for both stimuli. Results are discussed with reference to previous studies of syllabic pitch perception. PMID- 2913564 TI - Color correspondence in apparent motion. AB - To maintain figural identity during motion perception, the visual system must match images over space and time. Correct matching requires a metric for identifying "corresponding" images, those representing the same physical object. To test whether matching is based on achromatic (black/white) polarity and chromatic (red/green) color, observers viewed an ambiguous motion display and judged the path of apparent motion. Matching preserved black/white identity regardless of whether frames were viewed binocularly or dichoptically. Red/green identity was also preserved, but coherence of motion depended in part on the number of frames in the motion sequence and on the background luminance. These results suggest that correspondence is computed by a weighted metric containing terms for image features coded early in visual processing. PMID- 2913565 TI - Auditory discrimination of tone-pulse onsets. AB - Two experiments are reported in which difference limens (DLs) were measured for onset times of a 1000-Hz tone pulse. An adaptive two-alternative forced-choice procedure and (mostly) well-trained subjects were used. In the first experiment, DLs were measured for the rise time of linear onset ramps at rise-time values between 10 and 60 msec. The DLs follow Weber's law up to a rise time of about 50 msec, and do not support the notion that rise times are perceived in a categorical manner. In the second experiment, DLs were obtained for linear, exponential, and raised-cosine onset envelopes at rise-time values between 10 and 40 msec. When energy differences in the critical band around 1000 Hz are computed for just-discriminable onsets, values between 0.7 dB (10-msec rise time) and 0.3 dB (40-sec rise time) are found. These equivalent intensity DLs show the same "near miss to Weber's law" behavior as do intensity DLs for pure tones. PMID- 2913566 TI - A comparison of discrimination and identification of vibrotactile patterns. AB - Both discrimination and identification tasks have been used to assess subjects' abilities to perceive vibratory spatial patterns presented to the skin. The present study examined discrimination and identification performance under comparable conditions. In Experiment 1, subjects attempted to discriminate a pair of patterns on some blocks of trials and to identify both members of a pair on other blocks. For both tasks, the time between the members of the pair was varied. Discrimination performance could be predicted accurately from identification data. Analysis of performance on identification trials indicated that subjects used discriminability information to identify pairs. In Experiment 2, discrimination and identification were compared when the temporal separation between patterns was fixed and a masking stimulus followed each pattern after a variable delay. Results suggest that temporal masking, rather than the time available for processing pattern information, is the major limitation in both discrimination and identification of sequences of tactile patterns. PMID- 2913567 TI - Perception of slant-in-depth is automatic. AB - Two experiments assessed perception of the slant-in-depth of static irregularly contoured shapes when attention was withdrawn from processing slant-in-depth. The experiments showed that when the memory load of the experimental task is minimal, discrimination of slant-in-depth is evidenced even when attention has not been directed to slant discrimination. The findings are brought to bear on a model of perceiving shape-at-a-slant (Epstein & Lovitts, 1985) that partitions the components of the process into automatic and attention-demanding operations. PMID- 2913568 TI - The role of visual information in the processing of place and manner features in speech perception. AB - Visual information provided by a talker's mouth movements can influence the perception of certain speech features. Thus, the "McGurk effect" shows that when the syllable (bi) is presented audibly, in synchrony with the syllable (gi), as it is presented visually, a person perceives the talker as saying (di). Moreover, studies have shown that interactions occur between place and voicing features in phonetic perception, when information is presented audibly. In our first experiment, we asked whether feature interactions occur when place information is specificed by a combination of auditory and visual information. Members of an auditory continuum ranging from (ibi) to (ipi) were paired with a video display of a talker saying (igi). The auditory tokens were heard as ranging from (ibi) to (ipi), but the auditory-visual tokens were perceived as ranging from (idi) to (iti). The results demonstrated that the voicing boundary for the auditory-visual tokens was located at a significantly longer VOT value than the voicing boundary for the auditory continuum presented without the visual information. These results demonstrate that place-voice interactions are not limited to situations in which place information is specified audibly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2913569 TI - The vista paradox: a natural visual illusion. AB - Suppose an observer views a distant object through a window in the far wall of a room or corridor--a visual scene constituting a vista. If the observer moves toward the window, then the distant object will shrink in apparent size and appear farther away. These effects are paradoxical, because the distant object appears smaller as its visual angle increases. The vista paradox occurs under many other real-world conditions, such as viewing a distant object while moving out of the mouth of a valley, or driving across a topographic crest. In the present study, framing effects and the equidistance tendency are considered as possible factors. However, an explanation based on the dynamic relationship between the visual angle of the framing portion of a vista and the visual angle of a distant object appears more promising. PMID- 2913571 TI - Instructional and probability manipulations of bias in multiletter matching. AB - Ratcliff (1985) performed fits of his diffusion model to the results of multiletter-matching experiments conducted by Ratcliff and Hacker (1981) and Proctor, Rao, and Hurst (1984), in which bias to respond "same" or "different" was manipulated by instructions and probabilities, respectively. The fits showed that both bias manipulations affected settings of a goodness-of-match criterion, whereas instructions also affected sensitivity. Evaluations of the experimental procedures and of Ratcliff's model-fitting procedures were performed in the present study. Three experiments showed that instructions and probabilities had similar effects, regardless of whether the different pairs were blocked or randomized according to the number of mismatching positions. The most salient feature of the results--that "same" reaction times were traded off more than were "different" reaction times, with no corresponding asymmetry in the error rates- was evident in all situations. The evaluation of Ratcliff's model-fitting procedures indicated that the apparent influence of instructions on sensitivity likely is an artifact of unequal variance for the sets of same and different pairs. Moreover, the effects of bias can be explained in terms of settings of response criteria, rather than of the goodness-of-match criterion, as in Ratcliff's fits. PMID- 2913570 TI - Texture perception in sighted and blind observers. AB - The purpose of the present study was to evaluate the utility of visual imagery for texture perception. In Experiment 1, sighted, early-blind, and late-blind observers made relative smoothness judgments of abrasive surfaces using active or passive tough. In Experiment 2, subjects compared vision and touch in the accuracy of smoothness detection, using a broad range of textures, including very fine surfaces. No differences appeared between the sighted and the blind, and it did not matter if touch were active or passive. Vision and touch showed similar performance with relatively coarse textures, but touch was superior to vision for much finer surface textures. The results were consistent with the notion that visual coding of tactual stimuli is not advantageous (or necessary) for texture perception, since touch may hold advantages for the detection of the smoothness of surfaces. PMID- 2913572 TI - An investigation of the facilitation of simple auditory reaction time by predictable background stimuli. AB - Two experiments explored a surprising result reported by Emmerich, Pitchford, and Becker (1976): Simple reaction time (RT) to an auditory stimulus can be facilitated by the presence of a tonal background (or masker). In the first experiment, simple RT to a tonal signal was investigated for a variety of background frequencies and loudness levels, and significant facilitation of RT was found for low levels of the background. In the second experiment, no evidence of facilitation was found when the background stimulus was a randomly varying narrow-band noise, although evidence for facilitation was again found with a constant tonal background. PMID- 2913573 TI - Classification behavior and measures of intelligence: dimensional identity versus overall similarity. AB - Individuals tend to adopt either analytic or holistic modes of categorizing objects. In two studies, we examined the relation between these categorization tendencies and cognitive abilities as measured by standard psychometric instruments. The participants in both studies were pretested with a restricted classification task in which it was possible for them to classify simple stimuli by dimensional identity or overall similarity. Those making a large number of either type of categorization were then tested with subtests of the WAIS-R and with the Raven's progressive matrices. Across both studies, the analytic individuals (many dimensional identity classifications) scored higher than the holistic individuals (many overall similarity classifications) on some but not all of the subtests. The results are consistent with the idea that holistic modes of categorization may be more "primitive" than analytic modes. The findings are discussed in terms of the association between categorization mode and either general or specific cognitive abilities. PMID- 2913574 TI - Cross-modal, auditory-visual Stroop interference: a reply to Cowan and Barron (1987). AB - This series of experiments was performed to verify Cowan and Barron's (1987) reported effect of auditory color-word interference on a visual Stroop task. Extant theory predicts effects of irrelevant speech on visual memory tasks involving immediate, ordered recall of the items. Interference between the two sources of information (visual and auditory) is assumed to be located at the phonological store component of the articulatory loop. Perceptual tasks such as the Stroop task, which do not require use of the articulatory loop for rehearsal purposes, should not be similarly susceptible. The present data fail to replicate Cowan and Barron's findings, and are thus consistent with contemporary theory. PMID- 2913575 TI - The reality of cross-modal Stroop effects. PMID- 2913576 TI - Brightness contrast, brightness constancy, and the ratio principle. PMID- 2913577 TI - Qualitative relationships are decisive. PMID- 2913578 TI - Shoulder kinesthesia after anterior glenohumeral joint dislocation. AB - The purpose of this study was to examine kinesthesia in normal (uninjured) shoulders and in shoulders with a history of glenohumeral joint dislocations. Both shoulders of 10 healthy subjects and 8 subjects with a history of unilateral anterior dislocation were tested for accuracy of angular reproduction, threshold to sensation of movement, and end-range reproduction using a motor-driven shoulder-wheel apparatus. An analysis of variance revealed significant differences (p less than .001) between the injured and uninjured shoulders for all three tests. Post hoc analysis showed significant differences (p less than .02) between the involved shoulders and all uninvolved shoulders. No significant difference was found among the uninvolved shoulders. The results of this study indicate that kinesthetic deficits occur after glenohumeral dislocation and may result in abnormal neuromuscular coordination and subsequent reinjury of the shoulder. Clinicians should consider rehabilitation of shoulder kinesthesia using therapeutic activation of the shoulder joint and muscle receptors when treating patients with previous dislocations. PMID- 2913579 TI - Use of ultrasound to enhance percutaneous absorption of benzydamine. AB - The influence of ultrasound on the percutaneous absorption of benzydamine hydrochloride from a gel base was investigated in a double-blind, placebo controlled clinical study of 10 healthy volunteers. Using two similar experimental protocols, the effect of both 1:1 (2 msec on, 2 msec off) pulsed output ultrasound (3.0 MHz at 1.0 W/cm2 and 0.0 W/cm2 [control]) and continuous output ultrasound at a range of frequencies (0.75, 1.5, and 3.0 MHz at 1.5 W/cm2) were investigated. A placebo control (benzydamine gel massaged with ultrasound applicator switched off) was incorporated into each protocol. Percutaneous absorption of benzydamine was assessed by measurement of the residual amount of drug in the formulation base after treatment. Drug assay was by reversed-phase high-performance liquid chromatography and ultraviolet detection. Statistical analysis of the results for both continuous and pulsed ultrasound treatment showed that no significant differences existed between data for ultrasound treatment versus no ultrasound. In conclusion, although phonophoresis has been alleged to enhance percutaneous absorption of numerous drugs, ultrasound did not enhance the percutaneous absorption of benzydamine under the experimental conditions of this study. PMID- 2913580 TI - Effects of upper limb immobilization on isometric muscle strength, movement time, and triphasic electromyographic characteristics. AB - The effects of short-term immobilization on isometric muscle strength, movement time, and triphasic integrated electromyographic characteristics were assessed during a simple ballistic elbow flexion and extension movement. The nondominant upper limbs in six subjects (two female, four male) were immobilized in a plaster cast for 14 days. Testing consisted of isometric muscle strength output of elbow flexors and extensors; movement time; and IEMG output of the agonist, antagonist, and second agonist contractions during the ballistic movements. An analysis of variance revealed a decrease in flexor strength of the casted limb (p less than .05). Movement time was not significantly slowed. Antagonist IEMG amplitude was decreased (p less than .01) during flexion, and agonist IEMG amplitude (p less than .05) and antagonist IEMG amplitude (p less than .05) were diminished during extension of the casted limb. In conclusion, short-term upper limb immobilization affects primarily elbow flexion strength and some IEMG characteristics during a ballistic forearm movement, suggesting an influence on the neuromuscular aspects of the affected muscles. PMID- 2913581 TI - Effect of altering handle position of a rolling walker on gait in children with cerebral palsy. AB - The purpose of this study was to determine whether altering the handle position on a rolling walker would affect the gait pattern of children with spastic cerebral palsy (CP). Sixteen children with CP (2-10 years old) performed six gait trials, three with the handle on the rolling walker positioned horizontally and three with the handle positioned vertically. Using the footprint-on-paper method, gait characteristics of right and left step width, step length, and stride length; cadence; and velocity were determined. A two-way analysis of variance for two repeated measures indicated no significant differences in the measured gait characteristics between handle positions. Significant differences between the first trial and subsequent trials for both horizontal and vertical handle positions were found using Duncan's multiple comparison test. This study suggests that in this sample of children, altering the handle position did not lead to any immediate statistically significant changes in the gait characteristics measured. Results suggest that walkers with vertical handles should not be prescribed under the assumption that the gait characteristics of the child using the walker will be changed. This study does not rule out other changes that might occur with the use of vertical-handled walkers. PMID- 2913582 TI - Influence of head-neck rotation on static elbow flexion force of paretic side in patients with hemiparesis. AB - The purpose of this investigation was to examine the influence of bead and neck (HN) position in the transverse plane on the static production of elbow flexion force in the involved (paretic) upper extremity of patients with hemiparesis. Thirty-one patients who had experienced a cerebrovascular accident a mean of 44 days before testing participated in the study. Static elbow flexion force was tested with a hand-held dynamometer, twice with the HN rotated toward the paretic side and twice with the HN rotated toward the nonparetic side. Elbow flexion force did not differ with the HN in the two positions (F = 0.008, p = 931). Results of this study support the conclusion that HN position in the transverse plane does not influence the production of static elbow flexion force on the paretic side in patients with stroke. Clinicians, therefore, may wish to reexamine any emphasis they place on HN position for facilitating elbow flexion force production on the paretic side of patients with hemiparesis. PMID- 2913583 TI - Peak torque-to-body weight ratios in the trunk: a critical analysis. AB - The purpose of this study was to document the relationships between body weight and isokinetic extension and flexion peak torque produced by the trunk musculature. Using a dynamometer, we collected isokinetic measurements during trunk flexion and extension at speeds of 60 degrees and 120 degrees/sec on 61 healthy subjects (29 men, 32 women; 20-60 years old) while standing. Extension and flexion peak torque measurements were calculated for each subject at each speed. Male and female subjects' data were analyzed separately. Each subject's body weight was paired with peak torque at each speed, and Pearson product-moment correlation coefficients (r) were calculated. The correlation coefficients ranged from .27 to .39 for extension and from .66 to .70 for flexion, establishing a positive linear relationship between body weight and each of the isokinetic measurements. Body weight accounted for very small proportions of the variance (as low as 7%-15% in extension isokinetic measurements). In attempting to use a client's body weight to predict isokinetic peak torque measurements, the clinician should be aware that a great deal of unaccounted for variance exists. We recommend that clinicians use other variables (eg, activity level, age) in addition to body weight to control for individual differences among healthy subjects when measuring isokinetic trunk extension muscle performance. PMID- 2913584 TI - Comparison of gait of young men and elderly men. AB - The purpose of this study was to describe and compare the free-speed gait characteristics of healthy young men with those of healthy elderly men. Data collection consisted of high-speed cinematography resulting in synchronized front and side views of 24 healthy male volunteers, 12 between 20 and 32 years of age and 12 between 60 and 74 years of age. Young men were recruited to match the elderly men on the basis of right-leg length. Each subject participated in three filmed trials of free-speed ambulation down a 14-m walkway. The processed film was analyzed for eight gait characteristics. Differences in characteristics between the two groups were examined using a correlated t test (p less than .01). No significant differences were observed between the groups for step and stride length, velocity, ankle range of motion, vertical and horizontal excursions of the center of gravity, and pelvic obliquity; however, the younger men demonstrated a significantly larger stride width than the elderly men (p less than .01). The results suggest that the two populations of healthy adult men have similar gait characteristics. PMID- 2913585 TI - Effects of foot orthoses on center-of-pressure patterns in women. AB - The purpose of this study was to determine the effects of foot orthoses on the pattern of center of pressure in women with forefoot deformities during walking. Nine subjects with a forefoot varus and nine subjects with a forefoot valgus walked across a force platform three times for each of the following five treatment conditions: 1) barefoot, 2) shoes only, 3) rigid orthoses with shoes, 4) semi-rigid orthoses with shoes, and 5) soft orthoses with shoes. Force data were analyzed to determine the area under the center-of-pressure curve. A significant omnibus F ratio was obtained for treatments (p less than .001) and the deformity X treatments interaction (p less than .05) using a two-factor, mixed analysis of variance for repeated measures. Tukey's post hoc comparisons for the Varus Group resulted in significant differences (p less than .05) between the following treatment conditions: 1) barefoot and shoes only, 2) barefoot and rigid orthoses with shoes, 3) barefoot and semi-rigid orthoses with shoes, and 4) barefoot and soft orthoses with shoes. Tukey's post hoc comparisons for the Valgus Group resulted in significant differences (p less than .05) between the following treatment conditions: 1) barefoot and rigid orthoses with shoes, 2) barefoot and semi-rigid orthoses with shoes, and 3) barefoot and soft orthoses with shoes. The shoes-only treatment condition, in comparison with the barefoot condition, significantly reduced the center-of-pressure area for the Varus Group only.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2913587 TI - Diagnosis: defining the term. PMID- 2913586 TI - Problem-knowledge coupling: a tool for physical therapy clinical practice. AB - The purposes of this article are 1) to summarize the development, function, and philosophy of the Problem-Knowledge Coupler (PKC), a computerized tool that is designed to aid the clinical decision-making process in medical practice, and 2) to speculate on the value this system has in meeting clinical practice, needs and addressing professional practice issues in physical therapy. The evolution of the PKC system from its origins in the problem-oriented system of medical care is described, and the philosophy of problem-knowledge coupling is contrasted to the basic philosophy of traditional clinical medical practice and never computerized expert decision-support systems. We suggest that problem-knowledge coupling could be a useful tool in physical therapy because it improves the collection and synthesis of patient information and uses the unique nature of individual patient problems coupled with the clinical literature as the bases for clinical practice decisions. PMID- 2913588 TI - [Psychotherapeutic activity as a realization of therapeutic heuristics. A process comparison of 3 therapy forms from a new perspective]. AB - A new research perspective for analyzing the psychotherapeutic process is discussed. Instead of the usual method-oriented thinking, a heuristic understanding of psychotherapy is presented that focuses on the goals of therapeutic activity. The instrument developed for this purpose, the Heuristic Rating Scales, is described. Using data from a comparative treatment study, the suitability of these rating scales for analyzing therapeutic activity is tested statistically. Finally, the three therapy forms examined are described in terms of the realization in terms of the realization of therapeutic goals (heuristics) and compared with each other. PMID- 2913589 TI - [Temporal markers of analytic psychotherapy in relation to health insurance management]. AB - A sample (N = 1142) of applications for psychotherapy made at the health insurances was analyzed of characteristics as status of therapist, total number of sessions and weekly frequency of sessions. Analytic individual psychotherapy was the most often applicated (40%) of the four analyzed methods (depth psychologically founded respectively analytical, individual respectively group psychotherapy). With regard to individual analytic psychotherapy low-frequent therapies (one or two sessions weekly) are as usual as higher-frequent ones (three or four sessions weekly). Only 20% of these higher-frequent therapies seemed to last more than 240 sessions totally. PMID- 2913590 TI - [Control beliefs and patient compliance: an empirical study exemplified by adolescents with diabetes mellitus, bronchial asthma and alopecia areata]. AB - The present paper focuses on the relation between control beliefs and the compliance of adolescents suffering from chronical diseases. It is assumed that the compliance will be high when the own behavior is regarded as most important for the improvement during illness (internal locus of control). A high compliance is also expected when the own state of health is seen as dependent from other persons, who are engaged in the therapeutic process (powerful others locus of control). Little compliance is expected when the state of health is regarded as dependent from fate or chance influences (chance locus of control). Thereover, it is assumed that the control beliefs are influenced by the specific disease of a patient, since diseases are controllable by the patients in different degrees and therefore should result in specific control beliefs. The theoretical assumptions were proved in an empirical study with 80 patients suffering from different diseases (Diabetes mellitus, Asthma bronchiale, Alopecia areata) and 366 healthy adolescents and adults. The results show a clear dependency of the control beliefs from the kind of disease of the patients. However, the relations between control beliefs and compliance are discrepant to the expectations which is shown mainly by null or negative correlations between internality and compliance. The empirical relations are explained by the self-reliant behavior of the internal patients which perhaps shows little compatibility to traditional concepts of compliance. The implications of the present results for the enhancement of compliance and for the definition of the compliance-concept are elaborated and discussed. PMID- 2913591 TI - [Current developments in the area of consultation/liaison psychiatry. Information, definition of the concept, perspectives]. AB - Recent developments in cooperation of clinical and psychosomatic medicine are reviewed for the Federal Republique of Germany and the European neighbour countries. Central are: Development of concepts and modes of cooperation. The starting point are consultations, the goal is to "liaison" with most clinical areas. Research is focussed on: Dynamics of the process of cooperation, efficacy and efficiency as well as interactions of clinical course and coping. International comparison sheds more light on the relationship of psychiatry and psychosomatics/psychotherapy. The further development will try to stabilise existing cooperations as well as experiences from university medicine to every day clinical practise. The newly founded European Consultation Workgroup prepared a European collaborative study as well as a first European conference on consultation liaison. PMID- 2913592 TI - A manic episode in the course of anorexia nervosa with bulimia. PMID- 2913593 TI - ECT treatment of an elderly mentally retarded man. PMID- 2913594 TI - Bradycardia induced by an interaction between phenelzine and beta blockers. PMID- 2913595 TI - Anorexia nervosa and reflex sympathetic dystrophy syndrome. PMID- 2913596 TI - Treating chronic pain. PMID- 2913597 TI - Vomiting, chemoreceptor trigger zone, and dopamine. PMID- 2913598 TI - Anxiety, depression, and somatization in DSM-III hypochondriasis. AB - To assess the severity of distress and of somatization in hypochondriasis, the authors administered several validated self-rating scales of depression, anxiety, somatic symptoms, and anger/hostility to 21 psychiatric outpatients with the DSM III diagnosis of hypochondriasis and to matched groups of other nonpsychotic psychiatric patients, family practice patients, and employees. Anxiety and somatic symptoms were highest in hypochondriacal patients; depression and anger/hostility did not differ from those of other psychiatric patients but were higher than in the other groups. The findings do not support the theory that hypochondriasis is a defense against anxiety or that it is a masked depression or depressive equivalent. The findings are consistent with the view that the interaction of severe anxiety and severe somatic symptoms is a common feature of the psychopathology of hypochondriasis. PMID- 2913599 TI - Geriatric psychiatry patients' care by primary care physicians. AB - Primary care physicians were surveyed regarding their perceptions from recall of psychiatric disorders in, and their use of treatment approaches for, their geriatric patients. Affective disorders, organic mental syndrome, and generalized anxiety disorders were the three most common problems reported, and they were felt to be among the three most common problems by 89%, 56%, and 39% of the physicians, respectively. The three most common disorders for which they sought psychiatric consultation or referral were affective disorders, "psychosis," and organic mental syndrome, by 61%, 22%, and 18% of the respondents. The use of various psychiatric treatments and various sources of consultation and referral are analyzed and reported by age, primary care specialty, and practice setting of responding physicians. PMID- 2913600 TI - Sexual abuse in patients with anorexia nervosa and bulimia. AB - Few studies have documented the extent and nature of sexual abuse among women who later come to treatment for anorexia nervosa or bulimia. This comparison study reports on a sample of 158 patients admitted to an eating-disorder unit, of whom 60 gave a history of sexual abuse, compared to 98 with no history of abuse. Fifty percent of the anorexic and bulimic patients had suffered sexual abuse, compared to only 28% of patients admitted with other eating-disorder diagnoses; this was a significant difference (p less than 0.001). Of the four types of abuse surveyed, only those patients suffering rape were likely to have sought help from caregivers prior to admission (p less than 0.001). The authors report on likely perpetrators of abuse, age of first abuse, and frequency of depressive symptoms in the abused population. The data from this study strongly suggest that the possibility of sexual assault or abuse must be assessed and the results included in a comprehensive therapy plan for eating-disorder patients. PMID- 2913601 TI - Vulnerability and the psychological disturbances of cancer patients. PMID- 2913602 TI - Parkinson's disease, depression, and the on-off phenomenon. PMID- 2913603 TI - ECT following craniotomy. PMID- 2913604 TI - The electronic spectrum of adenine by electron impact methods. AB - The electron energy loss spectrum of adenine has been recorded over an excitation energy range of approximately 3-22 eV for scattering angles of 3 degrees and 6 degrees. In addition to reporting accurate vapor phase peak positions, the present work supports the long-held contention that the group of peaks in the 6- to 10-eV range belong to transitions that originate from valence pi orbitals. In the vapor phase spectrum, a Rydberg transition corresponding to an n----3s excitation is readily observed with a term value of 3.45 eV relative to the first long-pair ionization potential. PMID- 2913605 TI - Neutron-energy-dependent oncogenic transformation of C3H 10T1/2 mouse cells. AB - The relative biological effectiveness (RBE) of a range of neutron energies relative to 250-kVp X rays has been determined for oncogenic transformation and cell survival in the mouse C3H 10T 1/2 cell line. Monoenergetic neutrons at 0.23, 0.35, 0.45, 0.70, 0.96, 1.96, 5.90, and 13.7 MeV were generated at the Radiological Research Accelerator Facility of the Radiological Research Laboratories, Columbia University, and were used to irradiate asynchronous cells at low absorbed doses from 0.05 to 1.47 Gy. X irradiations covered the range 0.5 to 8 Gy. Over the more than 2-year period of this study, the 31 experiments provided comprehensive information, indicating minimal variability in control material, assuring the validity of comparisons over time. For both survival and transformation, a curvilinear dose response for X rays was contrasted with linear or nearly linear dose responses for the various neutron energies. RBE increased as dose decreased for both end points. Maximal RBE values for transformation ranged from 13 for cells exposed to 5.9-MeV neutrons to 35 for 0.35-MeV neutrons. This study clearly shows that over the range of neutron energies typically seen by nuclear power plant workers and individuals exposed to the atomic bombs in Japan, a wide range of RBE values needs to be considered when evaluating the neutron component of the effective dose. These results are in concordance with the recent proposals in ICRU 40 both to change upward and to vary the quality factor for neutron irradiations. PMID- 2913606 TI - Vascular and epithelial damage in the lung of the mouse after X rays or neutrons. AB - The response of the lung was studied in CFLP mice after exposure of the whole thorax to X rays (250 kVp) or cyclotron neutrons (16 MeV deuterons on Be, mean energy 7.5 MeV). To measure blood volume and leakage of plasma proteins, 51Cr labeled red blood cells and 125I-albumin were injected intravenously and 24 h later lungs were lavaged via the trachea. Radioactivities in lung tissue and lavage fluid were determined to estimate the accumulation of albumin in the interstitial and alveolar spaces indicating damage to blood vessels and alveolar epithelium respectively. Function of type II pneumonocytes was assessed by the amounts of surfactant (assayed as lipid phosphorous) released into the lavage fluid. During the first 6 weeks, lavage protein and surfactant were increased, the neutron relative biological effectiveness (RBE) being unity. During pneumonitis at 12-24 weeks, surfactant levels were normal, blood volume was decreased, and both interstitial and alveolar albumin were increased. Albumin levels then decreased. At late times after exposure (42-64 weeks) alveolar albumin returned to normal but interstitial albumin was still slightly elevated. Values of RBE for changes in blood volume and interstitial and alveolar albumin at 15 weeks and for changes in blood volume and interstitial albumin at 46 weeks were 1.4, comparable with that for animal survival at 180 days. The results indicate that surfactant production is not critical for animal survival. They suggest that changes in blood vessels and alveolar epithelium occur during acute pneumonitis; epithelial repair follows but some vascular damage may persist. The time course of the changes in albumin levels did not correlate with increases in collagen biosynthesis which have been observed as early as 1 month after exposure and persist for up to 1 year. Furthermore, a dose which had no effect on leakage caused a marked increase in collagen biosynthesis. Thus the present results do not support a causal relationship between exudation of vascular protein during pneumonitis and the later development of fibrosis. PMID- 2913607 TI - Radiation factors and their influence on induction of oxygen resistance. AB - Shortly after gamma irradiation, flour beetles exhibited a decline in resistance to oxygen toxicity. Then, about 2 weeks after irradiation, the 50% lethal dose (LD50) exposure time in pure oxygen was much greater than that of nonirradiated beetles, and this enhanced resistance persisted for about 6 months. The magnitude of the enhancement was a function of dose, decreased with increasing age at irradiation, and was modified by radiation factors. Both dose protraction and dose fractionation reduced the development of oxygen resistance to approximately the same degree that it reduced acute radiation lethality. This suggests that both the initial sensitization and the later enhancement of resistance are correlated with the residual biological damage rather than with the physical dose or initial damage. PMID- 2913608 TI - Radiosensitization of human colorectal tumor cells by 4-nitro-5 sulfonatoimidazoles. AB - Misonidazole, a clinically-effective 2-nitroimidazole hypoxic cell radiation sensitizer, and 12 4-nitro-5-sulfonatoimidazoles were tested in cultured human SW1116 colorectal adenocarcinoma cells for radiosensitizing efficiency. Octanol water partition coefficients and HPLC capacity factors were determined for all agents as measurements of lipophilicity, and an excellent correlation was found between the two measurements. Cytotoxicity, in vitro glutathione reactivity, and one-electron reduction potential were also determined for each compound to evaluate potential utility as macromolecularly transported radiosensitizers. Ten members of the set were found to be 40 to 300 times more radiotoxic than misonidazole, but no correlation was found between their radiosensitizing efficiencies and the chemical and physical parameters. PMID- 2913609 TI - Biochemical mechanisms underlying the development of radioresistance by cultured peritoneal exudate macrophages. AB - We investigated changes in radiosensitivity of peritoneal exudate macrophage colony-forming cells (PE-CFC) when exudative peritoneal macrophages were cultured in vitro. The change in the shape of the dose-response curve of PE-CFC to ionizing irradiation was partly dependent on the concentration of oxygen in the gas phase of the incubators. When cells were incubated in an environment containing 20% oxygen, the value of both Dq and D0 for PE-CFC increased. The dose response curve of PE-CFC cultured for 3 days resembled that of alveolar macrophage colony-forming cells (AL-CFC). The changes in radiosensitivity were accompanied by an increase in the level of three antioxidant enzymes: superoxide dismutase, catalase, and glutathione peroxidase. However, when they were cultured in a 6% oxygen environment, only the value of Dq increased. When alveolar macrophages were incubated in vitro, no significant change in the shape of the dose-response curve of AL-CFC was noted whether they were cultured in gas phase containing either 20 or 6% oxygen. It is concluded that the radiosensitivity of PE-CFC changes when they are cultured in vitro. The increase in D0 appears to be related to the intracellular level of antioxidant enzymes. PMID- 2913610 TI - Cell proliferation as a requirement for development of the contact effect in Chinese hamster V79 spheroids. AB - Chinese hamster V79 cells grown for several hours in suspension culture form spheroids which are more resistant to killing by ionizing radiation than cells grown on petri dishes, a phenomenon known as the "contact effect." Previous results using the alkali-unwinding assay as a measure of DNA damage have implicated differences in DNA conformation as contributing to this effect; spheroid DNA denatures more slowly in dilute alkali than monolayer DNA, perhaps due to the presence of constraints to DNA unwinding. In this paper, the rate of development of radiation resistance is shown to be similar when either cell survival or DNA unwinding is used as an end point. At the midpoint for development of resistance, approximately 10 h, the unwinding kinetics indicate that either half of the cells contain constraints to DNA unwinding, or half of the DNA in all of the cells contains constraints. The latter explanation appears more likely since all cells seem to develop these constraints at the same rate, regardless of position in the cell cycle or the degree of contact with other cells. Results using the microelectrophoresis assay to measure damage to individual nuclei confirm the fact that 10-h cultures show a homogeneous radiation response intermediate between that of monolayers and spheroids. Incubation of cells at room temperature or in the presence of drugs which inhibit cell cycle progression prevents full development of the contact effect. Conversely, incubation of cells in medium containing inhibitors of polyamine synthesis, adenylcyclase, glutathione synthesis, poly(ADP-ribose)polymerase, topoisomerase II, or cell-cell communication does not inhibit development of the contact effect as measured by DNA-unwinding kinetics. PMID- 2913612 TI - Case 7. Pelvic fibrolipomatosis. PMID- 2913611 TI - Analysis of the DS86 atomic bomb radiation dosimetry methods using data on severe epilation. AB - This report presents a reanalysis of the Hiroshima and Nagasaki data on severe epilation as an acute radiation effect using both the new DS86 and the old T65D dosimetries. The focus of the report is on several aspects of the data which have previously been examined by Jablon et al (ABCC TR 12-70, 1970) and Gilbert and Ohara [Radiat. Res. 100, 124-138 (1984)]. The report examines the uniformity of epilation response across shielding category, across sex and age, and in terms of interactions between city, sex, age, and shielding category; it also investigates the apparent relative biological effectiveness (RBE) of neutrons in the DS86 dose compared with the T65D dose, using both within- and between-city information. In addition the report discusses evidence for nonlinearity in epilation response. The epilation response function exhibits nonlinearity in terms of both a marked increase in slope at about 0.75 Gy, and then, beginning at about 2.5 Gy, a leveling off and eventual decrease in response. The principal conclusions of the report are as follows. The use of the DS86 dosimetry rather than T65D increases the apparent RBE of neutrons compared with gamma dose from approximately 5 to 10. At these values of RBE the slope of the dose response, in a middle range from 0.75-2.5 Gy, is about 165% greater using DS86 than T65D. With respect to the interactions of sex, city, and shielding method, the size and significance of virtually all nonuniformities in epilation response seem using T65D are also evident with DS86. Additionally it seems difficult to find any evidence that DS86 is an improved predictor of epilation response over T65D. Finally, the fact that the nonlinearity in dose response and apparent actual downturn in epilation occurrence rate at the high end of dose is more striking with DS86 than with T65D is found to be due primarily to the common practice of truncating all T65D doses to 600 rad. PMID- 2913613 TI - Case 8. Osteogenesis imperfecta tarda. PMID- 2913614 TI - Case 10. Vertebral (thoracic) chordoma. PMID- 2913615 TI - Technetium-99m hysterosalpingography in infertility: an accurate alternative to contrast hysterosalpingography. AB - Thirteen infertile women who had undergone tubal surgery within the previous year for the correction of tubal obstruction, were studied with both conventional and radionuclide hysterosalpingography. The studies were performed on the same day, were interpreted independently, and the results were then compared. Three cases were excluded from analysis because of the technical inadequacy of one of the studies. Assuming the findings of the conventional studies to represent "truth," the sensitivity, specificity and accuracy of the radionuclide studies were 100%, 60% and 80% respectively. PMID- 2913616 TI - Diaphyseal bone disease: scintigraphic-radiographic correlation. AB - Though generally nonspecific, the patterns of diaphyseal uptake of bone seeking radionuclides, when correlated with the radiographic findings and clinical histories, often suggest specific diagnoses and may obviate the need for further imaging. Diaphyseal uptake is considered in terms of "hot spots," unilateral long segment lesions and bilateral processes that may be symmetric or asymmetric in distribution. Scintigrams and corresponding radiographs of 18 different lesions are illustrated. PMID- 2913617 TI - A demonstration comparing film mammography with the new high sensitivity xeromammography. AB - The author has performed a subjective comparison of breast images recorded with a new liquid-toner xerographic system and images of the same breasts recorded on Kodak OM-1 film exposed with a MinR screen and a 5 to 1 grid. The xeromammograms are judged to be superior to the mammograms recorded on film with respect to: (1) the demonstration of calcifications, circumscribed masses, and the back of the breast; (2) the "resolution" of dense connective tissue; and (3) the overall image quality. Radiation doses to the breast associated with the two types of study are said to be comparable. Thirteen pairs of excellent images comparing xeromammograms with conventional breast films are presented. PMID- 2913618 TI - Computed tomography of chest wall masses. AB - The authors argue that CT is superior to other imaging techniques for the examination of the bones and soft tissues of the chest wall. They also note the importance of CT in planning therapy for lesions involving these structures. In support of these theses they present computed tomograms showing 26 different types of lesion involving the chest wall ranging from sternal fracture to malignant fibrous histiocytoma. Malignant neoplasms involving the chest wall by metastasis or direct extension from the breast, lung or mediastinum are emphasized. PMID- 2913619 TI - MR imaging: vascular anatomy of the abdomen. AB - In support of the thesis that MRI may replace more invasive angiography in some applications, a total of 28 MR sections are presented to illustrate the vascular anatomy of the abdomen in coronal, transverse and sagittal planes. More than 20 vessels are identified ranging in size from the aorta to the left inferior adrenal vein and the spermatic veins. There is no anatomic continuity in sections made in the coronal and transverse planes; sequential sections of a single patient are presented in sagittal and parasagittal planes, however. The polarity of the images is reversed for ease of comparison with angiograms. PMID- 2913620 TI - Image interpretation session. The Radiological society of North America 74th scientific assembly and annual meeting. November 27, 1988. Proceedings. PMID- 2913621 TI - Case 1. Hughes Stovin syndrome. PMID- 2913622 TI - Case 2. Primary malignant lymphoma of the heart. PMID- 2913623 TI - Case 3. Follicular thyroid carcinoma with metastases to bone. PMID- 2913624 TI - Case 4. Sarcomatoid renal cell carcinoma with osteogenic metaplasia. PMID- 2913625 TI - Case 5. Mycotic sinusitis caused by Bipolaris specifera. PMID- 2913626 TI - An open letter to hospital administrators. PMID- 2913627 TI - Performance evaluations that help nurses grow. PMID- 2913628 TI - Let patients be partners in their care. PMID- 2913629 TI - The high-pressure demands of compartment syndrome. AB - When increased pressure limits blood flow to muscles and nerves, prompt action is the key to preventing permanent disability. PMID- 2913630 TI - How much would you earn as an office nurse? AB - Office nurses are paid only about three-fourths the hourly rate hospital nurses receive. A survey of the physicians who employ them provides details on what these RNs are earning. PMID- 2913631 TI - Two stages of care for pleural effusion. AB - When the patient's pleural space is filled with fluid, palliative treatment measures--thoracic drainage and pleurodesis--and diligent nursing care can help her breathe easier. PMID- 2913632 TI - Drugs that keep AIDS patients alive. AB - A battery of once-obscure drugs is buying time for AIDS patients. Expect toxicity when you administer them, and know the interventions that can keep the patient's discomfort at a minimum. PMID- 2913633 TI - What's his ECG telling you? A guide for nurses (continuing education credit) AB - Knowing how to interpret an ECG will help every nurse--no matter what unit she works on--improve assessment skills and patient care. Here's how to organize your approach to mastering the basics. PMID- 2913634 TI - EP studies: when they're called for, what they reveal. AB - Electrodes in the right atrium, across the tricuspid valve, and at the right ventricle's apex give inside information on electrical activity. PMID- 2913635 TI - How you can use that federal report on nursing. AB - There are 16 recommendations and 81 strategies to alleviate the nursing shortage. Every nurse has a part to play in making goals like competitive salaries and nursing autonomy a reality. PMID- 2913636 TI - When a phone call is your liability lifeline. PMID- 2913637 TI - Don't let weight gain keep a smoker from quitting. PMID- 2913638 TI - How to create patient education tools. PMID- 2913639 TI - [Professional risk of infection by the AIDS virus]. PMID- 2913640 TI - [Microbiologic in vitro comparison of plaque-inhibiting mouthwashes]. AB - The colonization on rat molars of S. sobrinus OMZ 176, S. mutans OMZ 376, or a combination S. sanguis OMZ 9 and S. sobrinus OMZ 176 after a short exposition to various fluoride solutions and disinfectants was tested in vitro. The test solutions included Act, Candida, Veadent, sodium fluoride, amine fluoride, stannous fluoride, zinc fluoride hexetidine, stannous fluoride/amine fluoride solutions, chlorhexidine and water. The sterilized rat molars were immersed in the above test solutions for 60 seconds, then incubated with streptococci in broth for 8 hours, again dipped into the same test solutions for 60 seconds and reincubated for an additional 30 hours. The streptococcal suspension contained 14C labelled sucrose solutions. The deposits on the molars were dissolved in 6N potassium hydroxide during 16 hours. Finally, the beta rays emitted by the dissolved radiolabelled suspension were counted using a scintillation counter. The sodium fluoride containing solutions exerted no or a very limited effect on the bacterial deposits. In contrast to the other test solutions, sanguinaria extract (Veadent mouth rinse) mildly inhibited the S. sobrinus and S. mutans deposits, but plaque formation by the combination of streptococci was not hampered. Zinc fluoride/hexetidine, amine fluoride and stannous fluoride/amine fluoride solutions had a distinct and significant inhibitory effect on S. sobrinus and S. mutans deposits, but only a weak effect when mixed cultures were used for plaque formation. Chlorhexidine significantly inhibited the deposits of the three bacterial strains used in these experiments. PMID- 2913641 TI - Digital image processing in cephalometric analysis. AB - Digital image processing methods were applied to improve the practicability of cephalometric analysis. The individual X-ray film was digitized by the aid of a high resolution microscope-photometer. Digital processing was done using a VAX 8600 computer system. An improvement of the image quality was achieved by means of various digital enhancement and filtering techniques. PMID- 2913642 TI - No effect of waxed dental floss on enamel fluoride uptake or on enamel dissolution changes. AB - Enamel specimens were flossed in vitro with "waxed" dental floss and then treated with water, Act, Meridol, or Elmex Gel to evaluate the effect of "waxed" floss on the enamel fluoride uptake and on the enamel dissolution rate. The flossed and treated enamel was etched 4 times successively in 2N HCl for 5, 10, 15 and another 15 s. The concentrations of fluoride, calcium and phosphorus were assayed in the etching solutions. The enamel fluoride concentration was significantly increased in only the first layer of the Elmex Gel group compared to the other 3 groups. Respective etching depths were similar for the water, Act and Elmex Gel groups. However, the first layer in the Meridol group was less etched than that in the 3 other groups. This study showed that "waxed" dental floss did not compromise the fluoride uptake by surface enamel after treatment with a concentrated acidic topical fluoridating agent. Moreover, previously reported results showing that Meridol solution containing SnF2 and amine fluoride 297 significantly decreased the in vitro dissolution rate of enamel were confirmed by the present study. Even though the enamel was first treated with "waxed" dental floss, the SnF2/amine fluoride 297 still produced a decreased enamel dissolution rate. PMID- 2913643 TI - [Toxicology of amalgams. The information status of the Swiss population]. PMID- 2913644 TI - [Amalgam recovery from waste water]. PMID- 2913645 TI - [A control office for dental alloys and amalgams?]. PMID- 2913646 TI - Exercising choice. Case (almost) closed: fitness does seem to prolong life. PMID- 2913647 TI - Labeled therapy. A gene-transfer experiment may improve a cancer treatment. PMID- 2913648 TI - A tiny mouse came forth. PMID- 2913649 TI - Prominent ascending aorta. PMID- 2913650 TI - Diseases of the major thoracic vessels with emphasis on CT: Seminar A. PMID- 2913651 TI - Azygos lobe and azygos continuation of the inferior vena cava. PMID- 2913652 TI - Bowel perforation following microsurgical lumbar discectomy. A case report. PMID- 2913653 TI - Spinal epidural abscess following steroid injection for sciatica. Case report. PMID- 2913654 TI - Acute massive dural compression secondary to methyl methacrylate replacement of a tumorous lumbar vertebral body. PMID- 2913655 TI - Postoperative lordoscoliosis causing extrinsic compression of the right main stem bronchus and respiratory insufficiency. A case report. PMID- 2913656 TI - Spontaneous unstable burst fracture of the thoracolumbar spine in osteoporosis. A report of two cases. PMID- 2913657 TI - The perpendicular nerve root sign. PMID- 2913658 TI - Myelopathy secondary to spinal epidural lipomatosis. A case report. PMID- 2913659 TI - Enhancement of lumbar spine fusion by use of translaminar facet joint screws. AB - From January 1983 to March 1986 the authors have performed 88 consecutive lumbosacral spine fusion, enhanced with translaminar facet screws, as described by F. Magerl of St. Gallen, Switzerland. Forty-three patients have a follow-up of 12 months or greater, for a mean follow-up time of 16 months. The median time to fusion in this group was 6 months, with a range of 6 weeks to 10 months. Ninety three percent of the patients were found to be clinically improved, and 91% of patients were judged solidly fused on evaluation of motion radiographs. Compared with our previously reported results for lumbar fusion without internal fixation, supplementation of lumbar fusion by translaminar facet screw fixation significantly improved the clinical results, as well as the time required for fusion, with no significant increased risk. PMID- 2913660 TI - C6-7 dislocation in a neurologically intact neonate. A case report. PMID- 2913661 TI - Gas-filled intraspinal synovial cyst. A case report. PMID- 2913662 TI - Traumatic retrolisthesis of the lumbosacral junction. A case report. PMID- 2913663 TI - Failure to diagnose conus ependymomas by magnetic resonance imaging. PMID- 2913664 TI - Acro-osteolysis of the fingers in a spinal cord injury patient. A case report. PMID- 2913665 TI - Comparison of CT scan muscle measurements and isokinetic trunk strength in postoperative patients. AB - The present study compared the computed tomography (CT) scan muscle area/muscle density and isokinetic trunk strength of a group of spinal surgery patients (35 males and 11 females) 3 months postoperatively. Analyses showed trunk strength means to be below 50% of gender-specific "normal" values obtained by evaluating a normative sample. Extensor strength was more significantly affected than flexors. Single-cut CT scans performed at the time of isokinetic trunk strength assessment demonstrated psoas and erector spinae atrophy through a significant decrease in muscle density, with only a trend towards decreased cross-sectional area. Findings also indicated that there was a significant correlation between increased mechanical trunk strength performance and greater muscle density on CT scan. Strength was significantly lower for the male patients undergoing spinal fusion compared with those undergoing disc excision. However, no significant difference was found in strength measures between: males with high versus low pain level and working versus nonworking males at the time of evaluation. PMID- 2913666 TI - Clinical presentation of spinal cord concussion. AB - Spinal cord concussion is a transient disturbance of spinal cord function, with or without vertebral damage and no demonstrable pathologic changes, that results from a rapid change in velocity following trauma, and resolves within 48 hours. In a retrospective review of patients with spinal injury referred to a tertiary care center, spinal cord concussion was observed in 3.7% of patients. Thirteen cases are presented. A variety of clinical presentations may occur, all of which can be explained on the basis of the magnitude or direction of acceleration of the spinal cord. The cervical cord is most commonly affected, but concussion can occur at any level of the spinal cord. Spinal cord concussion is often associated with pre-existing vertebral abnormalities that result in narrowing of the spinal canal or areas of hypermobility. PMID- 2913667 TI - Simulift: a simulation model of human trunk motion. AB - In this paper, the authors present a deterministic simulation model, which they call Simulift, of trunk-muscle activity and intra-abdominal pressure during a sagittally symmetric trunk exertion. Simulift is a descriptive model that quantifies the time-varying loading of the spine based on observed internal forces. Recent findings about the time sequence of events during trunk motion and established equilibrium formulas provide the theoretical bases for the simulation. A profile of electromyographic activity in ten trunk muscles and intra-abdominal pressure is updated as simulated time passes, or as the trunk motion is simulated. Input to the model includes a list of motion-event times and a set of profile-component-behavior data. Simulift is an "impulse" model that computes instantaneous and time-integrated statistics on individual muscle activity, intra-abdominal pressure, compression, lateral shear, and anterior shear as the profile components of the simulated subject change. Computer results for the simulation model are presented. PMID- 2913668 TI - Estimation of lumbar disc areas by means of anthropometric parameters. AB - In order to standardize the results of different biomechanical studies concerning stresses on lumbar discs, it may be useful to estimate the disc dimensions of the examined subjects and to refer the stress values to a unit surface area (square centimeter). The association between anthropometric parameters and discal areas at the L3-L4, L4-L5 and L5-S1 levels, examined by computed axial tomography, was studied in a group of 32 subjects (16 male; 16 female) with the aim of estimating lumbar disc areas with a simple method. Bony structure weight, which is computed by an equation that takes into account the diameters of the wrist, elbow, knee, and ankle and the stature, is the anthropometric parameter best associated with the areas of lumbar discs. The wrist diameter also shows a good association with the same areas. On the contrary, the association between body weight and disc areas was found to be less adequate for this purpose. The equations of the relative regression lines are reported as well as the criteria for their practical applications. PMID- 2913669 TI - Intra- and postoperative complications in lumbar disc surgery. AB - In a prospective study, 412 primary and 69 reoperations for herniated lumbar disc were observed and intra- and postoperative complications compiled. Only surgeons with the experience of more than 100 surgical procedures on lumbar discs entered this study. The complication rates of the micro- and macrosurgical techniques are compared. Intraoperative complications range from 7.8% in the microdiskectomies and 13.7% in the macrodiskectomies to 27.5% in the reoperations. Postoperative complications range from 1.4% in reoperation, 3.9% in the microdiskectomies up to 4.2% in the macrodiskectomies. The risk of complications correlates with the age of the patient and the operating time. PMID- 2913670 TI - The influence on spinal cord evoked potentials of chymopapain applied to the rat lumbar spine canal. AB - Electrically evoked compound action potentials were used to quantify the neurophysiologic abnormalities caused by application of chymopapain into the lumbar spinal canal in rats. A branch of the sciatic nerve was stimulated with voltage impulses of constant amplitude (40 V) and duration (0.1 msec) at the right external malleolus. The responses were recorded at the dorsal root entry zone L1. The authors used different doses of chymopapain (low dose = 100 IU, middle dose = 250 IU, and high dose = 500 IU). The control rats were subjected to exactly the same stimulus and recording procedures, but the test solution was a corresponding volume of isotonic saline. The prolongation of the latency of the electrically evoked potential due to chymopapain is very clear at the doses of 250 IU and 500 IU, being about 10 to 15% relative to the mean latency before application of the drug. This study indicates that locally applied chymopapain has a dose-dependent effect on nerve conduction properties. PMID- 2913671 TI - Experimental instability in the rabbit lumbar spine. AB - The authors performed mechanical, biochemical, and histologic analyses of changes in the rabbit lumbar spine occurring after instability had been induced by facet removal to find whether this intervention produced an experimental model for intervertebral disc degeneration. Sham operated animals and an unoperated control group were used for comparison. Half of the operated animals were housed under conditions to promote higher physical activity than the other animals housed individually in small cages. Acutely, the removal of facet joints increased the flexibility of intervertebral joints. Over the following year, this increase in flexibility was reduced to close to control levels in all groups of animals. Within the intervertebral discs, there was no significant change in proportions or solubility of collagen or proteoglycans after surgery, nor was there microscopic or macroscopic evidence of disc degeneration. The surgical procedure produced hypermobility of the spine, but there was a subsequent restabilization, and the intended disc degeneration was not produced. These findings indicate that some as yet unidentified soft tissue repair process, facilitated by activity, overcame the hypermobility created at surgery, so degenerative changes in the intervertebral discs did not result. We suggest that other animal models of disc degeneration may represent a failure of reparative response to acute injury. PMID- 2913672 TI - Concordance of back surface asymmetry and spine shape in idiopathic scoliosis. AB - In order to determine why topographic methods have shown a poor correlation with radiographically measured scoliosis in clinical studies, the accuracy of detection of the presence, side, apex, and magnitude of a scoliosis curve was determined topographically (by moire fringe photography and by projected raster photography) in 104 patients attending a scoliosis clinic. The presence or absence of thoracic curves was correctly shown by the topograms in 77% of cases, and in the lower region (lumbar and thoracolumbar curves) in 79% of cases. For correctly identified curves, the greatest back surface rotation was, on average, 1.0 vertebral levels below the skeletal curve apex in the thoracic region and 0.5 levels below the apex in the lower region. The moire fringe with the greatest asymmetry occurred on average at 1.5 and 1.8 vertebral levels above the spinal apex in upper and lower regions, respectively. The magnitude of the Cobb angle was determined to within +/- 5 degrees in 24% of cases by moire measurements, and in 27% by the raster technique. The side of the scoliosis was incorrectly diagnosed by topography in ten patients with minimal or 'nonstandard' vertebral rotation. It was concluded that the presence, level, and side of a scoliosis curvature is well demonstrated by back surface topography in patients with 'standard' rotation, but the magnitude of the scoliosis cannot be determined from topograms sufficiently accurately for most clinical purposes. PMID- 2913674 TI - Computed tomographic investigation of the effect of traction on lumbar disc herniations. AB - The aim of this study was to evaluate the effect of static horizontal traction on disc herniations by computed tomographic investigation. Changes occurring under the effect of a traction load of 45 kg have been evaluated in 30 patients with lumbar disc herniation. The herniated nuclear material (HNM) has retracted in 11 (78.5%) of median, six (66.6%) of posterolateral, and four (57.1%) of lateral herniations. Clinical response of these cases to conservative treatment varied with the amount and location of HNM, the retraction of HNM, and calcification of protruded disc. Static lumbar traction showed variable effects on lumbar disc herniations, especially in relation with the amount and location of HNM. PMID- 2913673 TI - Limited surgical discectomy and microdiscectomy. A clinical comparison. AB - This study was performed in an attempt to determine if there was any clinical or cost benefit of microdiscectomy over surgical discectomy. Each patient was asked to rate his pain or neurologic deficit on a scale from 1 to 10 (1 = no pain or deficit and 10 = the most severe pain or deficit). Thirty patients underwent microdiscectomy. Average preoperative back pain was rated 8.03 and leg pain 8.53. Preoperative numbness was rated 5.29 and weakness 5.38. The median time off work preoperatively was 4 weeks. The mean hospitalization was 2 days, and a postoperative median of 8 weeks for returning to work. Average follow-up was 17.4 months. Mean back pain was 1.8, with 57% having no back pain at follow-up. Mean leg pain at follow-up was 1.3, with 67% having no leg pain. Numbness was rated 0.97, with 85% having none at follow-up. Weakness was rated 1.4, with 76% having none at follow-up. Thirty-four patients underwent surgical discectomy. Average preoperative back pain was rated 7.56 and leg pain 9.32. Preoperative numbness was rated 6.94 and weakness 5.88. The median time off work preoperatively was 6 weeks. The mean hospitalization was 7 days, and a median of 7 weeks postoperative before returning to work. Average follow-up was 18.5 months. The mean pain rating for back pain was 1.09, with 74% having no back pain at follow-up. The average leg pain was 1.09, with 74% having no leg pain at follow-up.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2913675 TI - Reconstruction of the lumbar spine using AO DCP plate internal fixation. AB - Augmentation of lumbar spine fusion with internal fixation using pedicle screw systems has gained wide currency because it offers rigid stabilization to foster fusion healing. The AO DCP plate has been employed in Europe as a spinal implant with pedicle fixation using 6.5 mm, full-threaded cancellous bone screws with success. This report details the experience of using this device for lumbar spine fusion in a series of 46 North American patients with a mean follow-up of 1.25 years (range 1-2.5 years). Thirty-one patients had had prior lumbar spine surgery with poor outcomes, and 15 had had no prior surgery. All were treated surgically for lumbar degenerative disease with canal decompression, internal fixation with AO plates, and fusion with autologous bone grafting posterolaterally. Complications included two early and one delayed wound infection; five cases of screw loosening; three cases of screw breakage; and three cases of screw impingement upon a nerve. Results of surgery in 17 patients with failed interbody fusion included good to excellent pain relief in 59%, and solid fusion in 76%. In 14 patients with failed posterior surgery the good to excellent pain relief rate was 79%, and the fusion rate was 86%. In 15 patients undergoing primary surgery there was 89% good to excellent pain relief and a solid fusion rate of 87%. The benefits accruing from augmentation of the fusion with internal fixation using AO DCP plates are positive and justify its continued use. Complications encountered in the early experience have been significantly reduced in subsequent series, indicating the existence of a "learning curve" effect which would mandate specific training of spinal surgeons in the technique. PMID- 2913676 TI - Strain in fibers of a lumbar disc. Analysis of the role of lifting in producing disc prolapse. AB - A three-dimensional nonlinear finite element model has been used to predict the strain in the disc fibers of a lumbar motion segment under various single and combined loads such as those representing symmetric and non-symmetric liftings. A progressive failure analysis also has been performed under loads representing lifting while bending to one side: assuming yield and ultimate fiber strains of 14 and 16%, respectively. Large tensile strains of about 10% in the disc fibers are predicted under the maximum loads simulating symmetric lifting. Addition of lateral bending and twisting significantly increases the maximum fiber strain to more than 20%, and hence augments the risk for disc rupture. The maximum fiber strain occurs in the innermost annulus layer at the posterolateral location. Loss of intradiscal pressure or volume has a marked diminishing effect on the magnitude of maximum fiber strain predicted under flexion loadings. Failure analysis indicates that rupture initiates in the fibers in the innermost layer at the posterolateral location. With a slight increase in the loads, rupture progresses radially to the adjacent outer layer. Further progress of rupture in the fibers toward the annulus outer periphery resulting in complete radial fissure and disc prolapse appears to require additional increase in the loads. In the presence of large intradiscal pressure, the generated partial or complete radial fissure is likely to result in annulus protrusion or disc herniation, respectively. The results of clinical, epidemiologic, and experimental studies support the failure mechanism predicted in the present study. PMID- 2913677 TI - Antineutrophil cytoplasmic auto-antibodies in the diagnosis and management of vasculitis. PMID- 2913678 TI - Medical microbiology and recombinant DNA. PMID- 2913679 TI - [An evaluation of the hematological response to iron dextran by pregnant women with iron deficiency]. AB - The haematological response after infusion of total and two-thirds doses of iron dextran (Imferon; Fisons) was studied in 31 pregnant women with iron deficiency in the second and third trimesters. The increase in serum ferritin values was found to be greater with the full dose than with the two-thirds dose. Although haemoglobin values and mean corpuscular volume improved, the response was not statistically significant. PMID- 2913681 TI - Standardisation of statistics for health service management. PMID- 2913680 TI - Management of term pregnancy with premature rupture of the membranes and unfavourable cervix. AB - Sixty pregnant patients at term, who had premature rupture of the membranes and an unfavourable cervix were randomised to compare expectant management with oxytocin induction and with the use of prostaglandin E2 vaginal tablets for cervical ripening/induction of labour. Patients treated expectantly were placed on bed rest and observed for labour and infection. Patients managed by intervention were given intravenous oxytocin or 2 prostaglandin E2 tablets (0.5 mg) intravaginally every 6 hours. Between the three groups the duration of labour was longer in the oxytocin group and all 6 caesarean sections were performed on patients in this group. There was only 1 case of proven neonatal sepsis; this occurred in the oxytocin group. Patients with prostaglandin cervical ripening had a shorter hospital stay compared with patients treated expectantly. It is concluded that prostaglandin-induced cervical ripening is the method of choice in handling term patients with premature rupture of the membranes and an unfavourable cervix. PMID- 2913682 TI - Observations on the use of some known and suspected toxic Liliiflorae in Zulu and Xhosa medicine. AB - The usage as well as some of the known family chemical characteristics of Xhosa and Zulu traditional medicinal plants belonging to various families of the superorder Liliiflorae are related to some of the clinical effects of Xhosa medicine observed by Solleder in 1972. Symptoms and effects of some fatal cases of human and animal poisoning are tabled. Fewer cases of acute poisoning appear to take place than might be expected. If hospital staff were seen to be more understanding in their attitude towards herbal medicine, tracing and eventually discouraging the use of harmful plants and practices might be easier. PMID- 2913683 TI - [Surrogate motherhood as a question in the context of a biomedical research ethic]. AB - The most important question in biomedical ethics is really whether a researcher should do what he can do. The interventional model of modern medicine, which makes medical decisions on medical grounds, can threaten human values. In a Christian perspective we are responsible to God for our humanity. Surrogate motherhood is a very complicated question which concerns the problem of childlessness. Biomedical ethics, in the Christian context, cannot merely condone surrogate motherhood as a human and standard medical procedure. Ethically speaking, an unqualified no or an unqualified yes cannot be given. The parents' motives for their decision and the quality of their marriage are of the greatest importance before a decision about surrogate motherhood can be reached. The position of the woman who undertakes to be a surrogate mother is also questionable. Pregnancy is not just physical fact, it is an existential and human concern. The human womb is thus more than just an organ--it is a part of a woman's identity. PMID- 2913684 TI - AIDS and the dentist. PMID- 2913685 TI - Action limits for serum cholesterol. PMID- 2913686 TI - [A persistent case of kennel cough caused by Filaroides osleri]. AB - A dog showing chronic symptoms of cough, which was treated for kennel cough for nearly twelve months, was found to be infected with Filaroides osleri. A single course of treatment with 0.2 mg/kg of ivermectin was followed by subsidence of the symptoms which disappeared within a fortnight. PMID- 2913687 TI - [Determination of estrone sulfate levels in the blood and urine of pigs]. AB - The concentration of oestrone sulphate was determined in plasma as well as in urine to verify early pregnancy in pigs (within 24-29 days after mating). The threshold level in plasma was 0.70 ngr/ml. and in urine 50 ngr/ml. Accuracy was ninety-nine per cent in samples of plasma and ninety-two per cent in samples of urine respectively. PMID- 2913688 TI - [Postpartum torsion of the right uterus horn in a cow]. AB - Four cases of torsion, 180 degrees to the left of the right uterine horn in cows are reported. Two cases appeared about the time of parturition, two within two and four weeks after parturition. The uterine horn was reducible following laparotomy in three animals. It had to be amputated in one case. The authors suppose the size of the uterus to be a factor in the pathogenesis of the uterine anomaly referred to. PMID- 2913689 TI - [A comparison of parrot food commercially available in The Netherlands]. AB - The composition of a number of parrot foods commercially available in the Netherlands was put to the test for the (partly hypothetical) needs of the larger psittacine birds such as African Grey parrots, Amazon parrots, macaws and cockatoos. These studies showed that the majority of the foods is multideficient. When the deficient foods are supplied to parrots without any additions, this will give rise to the appearance of disease. However, some of the products recently put on the market (Bogena and Kasper Fauna Food) comply better with the requirements of a 'complete parrot food'. As regards public enlightenment, food producers, petshops, consumer organisations and veterinarians are obviously responsible. PMID- 2913690 TI - [Effect of the laying nest on cortisone levels in the plasma of laying hens prior to oviposition]. AB - The effects of a laying nest on egg-laying behaviour and plasma corticosterone levels are described. Three causes of increasing corticosterone levels are discussed: (1) an increase during egg-laying behaviour; (2) an increase during oviposition; (3) an increase due to removal of the laying nest. PMID- 2913691 TI - [Persistent cough]. PMID- 2913692 TI - [Nature in the news (2)]. PMID- 2913693 TI - [Benveniste's study]. PMID- 2913695 TI - The traveling adventures of a traveling nurse. PMID- 2913694 TI - Perioperative care of the spinal cord injured patient. PMID- 2913696 TI - Bridging the nursing gap. PMID- 2913697 TI - Productive interpersonal communications. PMID- 2913698 TI - Increase efficiency with custom packs. PMID- 2913699 TI - [Freedom for research in Germany?]. PMID- 2913700 TI - [Modern possibilities of prosthetic management of the skeletal and locomotor system and its effect in assessing disability]. AB - After casting a retrospective glance at the history of total hip replacements models currently in use are surveyed. Reasons for aseptic loosening of different prosthesis models as well as the rate of loosening are discussed. After presenting own results it is attempted to give an indications list for various current types of prosthesis. Finally the consequences of insurance aspects are described. PMID- 2913701 TI - [The aged human as an accident patient]. AB - An older person has very limited resources at his disposal for physical and psychological compensation and he is thus particularly affected in the case of accident. Therapy must therefore be aimed at retaining or reestablishing the general mobility of the patient, above all his physical re-mobilization, within the shortest possible space of time. Practical consequences are discussed here. PMID- 2913702 TI - [Differentiation of "accident" and "accident sequelae" in private accident insurance]. AB - In legal and private accident insurance you can find a distinction between "accident" and "results of an accident". In the system of the AUB (general terms of accident insurance) the insurant's injury is a notional part of the accident, which has been criticized by some medical experts. In fact, this distinction could entail different meanings and interpretations of the term "results of an accident", especially in section 10.1 AUB. In the author's point of view, section 10.1 AUB is applicable whenever different factors due and not due to the accident combine to produce the injury or the further damage (e.g. death, disablement). PMID- 2913703 TI - Degeneration of cartilage canal vessels associated with lesions of osteochondrosis in swine. AB - Articular-epiphyseal cartilage complexes from the distal femur and humerus of five 3-month-old pigs were collected and preserved using either a conventional or a ruthenium hexammine trichloride (RHT)-supplemented fixation technique. Lesions were similar regardless of the fixation technique. Areas of necrosis were in epiphyseal but not articular cartilage from both sites of all pigs. Cartilage canals were confined to epiphyseal cartilage and contained vessels which had endothelial cells in varying stages of degeneration and necrosis. Areas of necrotic cartilage often were adjacent to or surrounded degenerate cartilage canals. Lipid emboli (up to 40.0 micron in diameter) were infrequently located in vessels within cartilage canals. Associated with the lipid emboli were leukocytes, erythrocytes, necrotic cell remnants, and flocculent material. Restriction of necrosis to epiphyseal cartilage and the association of these necrotic areas with degenerating vessels in cartilage canals strongly implicate a defect in cartilage canal blood supply in the pathogenesis of osteochondrosis. The RHT fixation technique resulted in excellent cellular detail at the light microscopic level, but ultrastructurally there was marked vacuolation of chondrocytes and matrix. The conventional technique caused shrinkage of all chondrocytes, resulting in a wide halo of pericellular matrix surrounding each cell. PMID- 2913704 TI - Increased levels of DNA synthesis in hyperplastic renal tubules of aging nephropathy in female F344/NCr rats. AB - Histoautoradiography was done to evaluate cell turnover by measuring levels of DNA synthesis in the different anatomic areas of the kidney in aging (76 to 103 weeks of age) female F344/NCr rats after injection of tritiated thymidine (3H thymidine). All areas showed increased 3H-thymidine labeling indices (LI), including cortical and medullary tubules and interstitium. The extent of increase was directly correlated with increasing severity of the nephropathy. Atrophic, degenerative, and hyperplastic cortical tubules in areas of nephropathy had LI eight to nine times greater than nonaffected areas and more normal kidneys. These observations suggest that the hyperplastic responses of renal tubules to the unknown etiologic agents of aging nephropathy may be similar to those of tubules responding to chemical toxins. PMID- 2913705 TI - Epididymal interstitial (Leydig) cell tumors in B6C3F1 mice. AB - Six primary interstitial cell tumors of the epididymis were identified from 46,752 male B6C3F1 mice used in chronic toxicity and carcinogenicity studies. Five of the tumors occurred at the end of 2-year studies; none were attributed to treatment. None of the mice with epididymal tumors had a primary testicular tumor. Histologically, tumors were characterized by a nodular or diffuse proliferation of tumor cells in the epididymal interstitium. Most cells were polygonal with highly vacuolated cytoplasm (vacuolated cells) or eosinophilic cytoplasm (eosinophilic cells). Smaller hyperchromatic cells with scant basophilic cytoplasm (basophilic cells) and cells with yellow-brown pigment characteristic of lipofuscin (pigmented cells) were less common. In each tumor two or more cell types were present. Extension of these tumors through the capsule, invasion of the testis, or metastasis did not occur. By electron microscopy both eosinophilic and vacuolated cell types had a large round or oval nucleus with sparse heterochromatin, abundant mitochondria with tubulovesicular cristae, and frequent desmosome structures between cell membranes. Vacuolated cells contained numerous lipid droplets. Morphological features of the epididymal tumors are similar to those of the testicular interstitial (Leydig) cell tumor in mice and rats. PMID- 2913706 TI - Hematological, osmotic, and scanning electron microscopic study of erythrocytes of dogs given beta-acetylphenylhydrazine. AB - Hematologic examinations, osmotic fragility tests, and scanning electron microscopy of erythrocytes were done on blood of dogs given 5 mg/kg of beta acetylphenylhydrazine for 5 weeks. Reticulocytes, Heinz bodies, and serum total bilirubin values increased in the 1st week. Reticulocyte numbers peaked in the 2nd week, and reticulocytosis persisted through the 5th week. Erythrocyte, packed cell volume, and hemoglobin values decreased markedly and became lowest in the 2nd week. Mean corpuscular volume increased in the 1st week and remained increased for the duration of treatment. Erythrocyte osmotic fragility was increased after 1 week of treatment. Echinocytes were increased with a peak level of 47.6% at week 1 of treatment. Increased numbers of acanthocytes and schizocytes also were detected. PMID- 2913707 TI - Ultrastructural pathology of hemopoietic organs in Trypanosoma vivax infection of goats. PMID- 2913708 TI - Radiographic examination of eyes fixed in Zenker's solution. PMID- 2913709 TI - Large granular lymphocyte tumor in a horse. PMID- 2913710 TI - Spontaneous gastric carcinoid tumor in an aged Sprague-Dawley rat. PMID- 2913711 TI - Multilobular osteosarcoma of the mandible and orbit in a dog. PMID- 2913713 TI - 4,055 pounds shed, salt cut. PMID- 2913712 TI - Renal dysplasia with multiple urogenital and large intestinal anomalies in a calf. PMID- 2913714 TI - Ischemic cerebrovascular disease in the young adult. Emergence of oral contraceptive use and pregnancy as the major risk factors in the 1980s. AB - Although oral contraceptives and pregnancy are recognized risk factors for stroke, epidemiological studies in young adults have not demonstrated these as the major risk factor of ischemic stroke in this age group. Our experience suggests that pregnancy and oral contraceptives have emerged as the major current risk factors for ischemic stroke in young adults. PMID- 2913715 TI - Adenocarcinoma of unknown primary site. AB - A retrospective review of 108 patients with adenocarcinoma of unknown primary site (ACUPS) seen at Charleston Area Medical Center from 1979 to 1987 was performed. The liver and bones were the most common presenting sites of metastases. Only three patients had their primary site found after extensive radiologic and endoscopic workup. The pancreas and biliary tract were the most frequent laparotomy or autopsy-proven primary sites. Four of the 27 patients treated with chemotherapy responded (14.8 per cent). Eleven of 12 patients who survived for longer than 12 months had predominantly localized disease which permitted local therapy (i.e. surgery and/or radiotherapy). The median survival of the entire cohort was four months. The search for the primary site should include investigation of the patients' signs and symptoms, and limited screening tests. PMID- 2913716 TI - Ruptured abdominal aortic aneurysm: the persistent challenge. AB - Despite improvement in anesthetic and postoperative care, ruptured abdominal aortic aneurysms (AAA) continue to have a high mortality. Thirty-three patients from 1980-1986 underwent surgery at West Virginia University for ruptured AAA, with 12 survivors (36.4 per cent). Age, use of MAST trousers, initial hemoglobin and blood pressure as well as operative time and estimated blood loss were not found to be significantly different between survivors and non-survivors. The blood pressure at the time of induction, during surgery, at the end of surgery, and the final temperature were significantly different. Our results show that the chance of survival is much greater if the patient responds to the initial fluid resuscitation prior to induction, and if blood pressure and temperature are maintained during the operation. PMID- 2913717 TI - Methotrexate therapy in rheumatoid arthritis. AB - Rheumatoid arthritis (RA) is a common disease with a significant economic and social impact on Americans. Many patients with RA are unresponsive to or intolerant of conventional therapy or the limited therapeutic options available. For many of those patients, immunosuppressive drugs have been the mainstay of therapy. Our experience with methotrexate for these patients indicates that this drug provides symptomatic relief and improvement in objective parameters. Significant toxicity was uncommon. Methotrexate should be considered for selected patients with severe rheumatoid arthritis when conventional measures have been exhausted. PMID- 2913718 TI - Spectator sensitivities. PMID- 2913719 TI - Wise words for physicians. PMID- 2913720 TI - Several dozen call AIDS hotline. PMID- 2913721 TI - Carnitine deficiency, mitochondrial dysfunction and the heart. Identical defect of oxidative phosphorylation in muscle mitochondria in cardiomyopathy due to carnitine loss and in Duchenne muscular dystrophy. AB - Cardiomyopathies are often caused by a metabolic defect. Carnitine deficiency and mitochondrial defects in the metabolism of acyl-CoA, including defects in oxidative phosphorylation, start the same circular mechanism of mitochondrial doom. Patients with cardiomyopathy due to carnitine loss are cured by carnitine supplementation. In such a patient we found defective oxidative phosphorylation in isolated muscle mitochondria. The stimulation of the respiratory rate with all substrates by ADP was decreased, probably the cause of inhibition of the adenine nucleotide translocator by accumulating long-chain acyl-CoA. The same condition was encountered in patients with Duchenne muscular dystrophy, who often get cardiomyopathy in the course of the disease process. PMID- 2913722 TI - [L-carnitine therapy and myocardial function in children treated with chronic hemodialysis]. AB - Six out of 14 chronically hemodialysed children with significantly decreased serum carnitine levels were substituted with L-carnitine (15-30 mg/kg/day Biocarn) up to normal and above normal carnitine levels. None of these patients were digitalised. During the time of investigation plasma carnitine levels were investigated monthly and, simultaneously, three echocardiographic parameters in M mode were quantitatively und qualitatively determined: shortening fraction (SF %), ratio of left ventricular pre-ejection/ejection time (LVPT/LVET) and velocity of circumferential fibre shortening (Vcf). Carnitine substitution produced measurable changes in echocardiographic parameters, and a significant quantitative improvement in left ventricular function and performance: after 6 months of carnitine substitution a 24% improvement was seen, after 18 months a 44% mean improvement. No side effects of carnitine were observed; the compatibility was good. Beside these positive effects all patients reported decreased dialysis-associated spasms and polyneuropathic symptoms and increased somatic ability. PMID- 2913723 TI - [Energy-supplying metabolism of the volume overloaded and hypoxia stressed heart in children]. AB - This study summarizes results obtained with regard to atrial and ventricular enzymes of energy supplying metabolism in children with different types of congenital heart disease. In all groups of patients - normoxemic as well as hypoxemic - significant atrio - ventricular differences were observed: the right ventricle is amply equipped for utilization and oxidation of all major nutrients, while the right atrium utilizes glucose predominantly. Myocardial metabolism in children with congenital heart disease was significantly influenced by hypoxemia: the capacity of aerobic enzymes in cyanotic patients was significantly lower, both in atrial and ventricular tissue, whereby the atrial changes were even more striking. No marked differences were found between atrial and ventricular septal defects in normoxemic patients; the only difference was a lower capacity of fatty acid catabolism in children with atrial septal defect. PMID- 2913724 TI - Endomyocardial fibrosis in the child. AB - Endomyocardial fibrosis is a rare disease in children and has been mainly observed in tropical Africa, seldom in Europe. Its precise aetiology remains unknown. New surgical procedures have recently led to better survival. Four children, a 5 year old Swiss boy and 3 African girls, aged 12 to 14 years, were submitted with global heart failure class III to IV of the NYHA classification. Two patients had eosinophilia on admission. A third had a history of transient eosinophilia. The echocardiographic examination showed a very typical picture. In 3 patients (2 f and 1 m) both ventricles were involved; in one girl only the left ventricle. Decreased ventricular distensibility with impaired filling of the left and/or right ventricle was present in all. Diastolic pressures ranged between 24 and 35 mmHg; the systolic function was satisfactory in 3 children (ejection fraction [EF] of 44 to 61%) and severely decreased in the fourth (EF 10%). Three patients underwent endocardectomy: both ventricles in 1 case, only the left in 2 cases. Mitral valve repair by means of the Carpentier ring was done once, valve replacement once (Starr-Edwards prothesis). One child died; the 2 surviving patients showed a distinct improvement in their clinical state and are now in class II of the NYHA classification. Echocardiographic and catheter investigations show, however, persistence of the restrictive cardiomyopathy. Thus, surgical intervention must be considered a palliative procedure in these cases. The diagnosis can clearly be made nowadays with bidimensional and Doppler echocardiography. PMID- 2913725 TI - [Serial determination of anthracycline poisoning in children]. AB - Dose-related cardiotoxicity limits enthracycline administration in patients with solid tumours or leukaemia. Many patients (70%) would probably benefit by receiving more than a total accumulative dose of 500 mg/m2. As a measure of myocardial function the left ventricular ejection fractions (EF) were determined from serial radionuclide angiograms in 62 children who had at least 3 studies (mean age 8.4 +/- 5.4 years). Seven patients who had clinical evidence of cardiac involvement and/or a marked decline in their EF underwent endmyocardial biopsy (9 x). The EF declined progressively from 63 +/- 7% prior to chemotherapy to 60 +/- 5%, 58 +/- 7% and 54 +/- 7% after low, medium and high-dose anthracycline, respectively in the non-biopsied children vs 58 +/- 4%, 54 +/- 7% and 48 +/- 4% in the biopsied patients. Anthracycline dosage was 129 +/- 42, 307 +/- 68 and 471 +/- 61 mg/m2 and 103 +/- 64, 303 +/- 73 and 536 +/- 93 mg/m2, respectively. The biopsies were obtained at a mean anthracycline dose of 408 mg/m2 when the EF was 46 +/- 5%, and graded according to the modified Billingham score; grade 1 (6 x), 1.5 (2 x) and 2.5 (1 x). A decline in the EF was seen in 89% of our patients throughout their chemotherapy course, with a statistical significance of p less than 0.02 in the biopsied patients after medium dose therapy which was not seen in the non-biopsied children until they were receiving anthracyclines. PMID- 2913726 TI - [Changes in fatty acid metabolism in dilated cardiomyopathy and hypertrophic cardiomyopathy in childhood]. AB - The aetiology and the pathomechanisms in both types of cardiomyopathy (CM) are still unknown. In vivo measurements of myocardial metabolism in CM may be useful, but there is hardly any information on this subject. Free fatty acids (FFA) are the main source of energy for the normal myocardium. A method for external measurement of the FFA extraction rate (FFA-ER) in different myocardial regions by the simultaneous use of two isotopes has been developed. 201 TI indicates the myocardial perfusion and 15-(p-123 I-phenyl)-pentadecanoid acid (IPPA) represents the FFA uptake. The relation of IPPA/TI reflects the FFA-ER. 8 patients with hypertrophic CM (HCM), age 0.2-20 years, and 8 patients with dilated CM (DCM), age 0.2-18 years were investigated. 12 healthy adults and 4 infants after an arterial switch operation were used as a control group. All patients with HCM showed normal myocardial perfusion but the FFA uptake was strongly diminished, resulting in a reduction in FFA-ER to 42 +/- 12% of the normal value. The maximal influx rate (IR) of FFA was diminished too. In patients with DCM both the myocardial perfusion and the FFA uptake were globally reduced, resulting in a virtually normal FFA-ER. The IR was slightly increased. In HCM and DCM FFA utilisation was disturbed. The alterations were significantly different in both types of CM and different pathomechanisms can be assumed. PMID- 2913727 TI - The development of the chondrocranium of Gallus gallus. AB - An account of six stages of the development of the chondrocranium up to the beginning of ossification is given. The tip of the chorda does not pierce the anterior surface of the acrochordal in the early stages and the fenestra basicranialis posterior develops through resorption of the basal plate. The posterior part of the orbital cartilage develops a laterally situated orbitocapsular commissure and a medially situated pila antotica spuria. The pila antotica is resorbed leaving the posterior orbital cartilage connected to the basal plate only by the pila antotica spuria. In the earliest stage the cochlear portion of the otic capsule is fused to the basal plate, but can be distinguished from the basal plate and the canalicular portion. The tectum synoticum is attached to the otic capsule by two roots with the ventral attachment spreading over the lateral surface of the pila occipitalis. The trabecula communis forms without the intervention of an intertrabecula. The interorbital and nasal septa develop from the trabecula communis. An ethmoid plate forms the roof of the nasal capsule and the rest of the capsule develops as outgrowths from the roof. A transitory floor for the posterior part of the nasal capsule is present in the young stages and an incomplete floor for the anterior part develops late during the ontogeny. PMID- 2913728 TI - Adipose fatty acid composition and the risk of serious ventricular arrhythmias in acute myocardial infarction. AB - The relation between subcutaneous adipose tissue fatty acid composition and serious ventricular arrhythmias during acute myocardial infarction was studied in 2 groups of patients. In group 1 (n = 42), studied retrospectively, patients with ventricular fibrillation or tachycardia had a higher concentration of long-chain saturated fatty acids than those without (32.5 +/- 0.8% vs 29.7 +/- 0.4% [mean +/ standard error of the mean], p less than 0.01). In a prospective study, patients with arrhythmias (n = 106) had higher levels of long-chain saturated fatty acids (32.1 +/- 0.5% vs 30.7 +/- 0.4%, p less than 0.05) and of stearic acid (4.9 +/- 0.2% vs 4.4 +/- 0.1%, p less than 0.02) and a lower concentration of palmitoleic acid (7.3 +/- 0.3% vs 8.1 +/- 0.2%, p less than 0.005). When peak plasma creatine kinase concentrations were included with the individual fatty acid levels in a multiple logistic regression, only creatine kinase correlated significantly with ventricular arrhythmias (p less than 0.01). Thus, saturated fatty acids in cardiac membranes may lead to greater vulnerability to ventricular arrhythmias, although infarct size is the only statistically significant predictor after multiple regression analysis. PMID- 2913729 TI - Comparison of mortality and myocardial infarction rates in stable angina pectoris with and without ischemic episodes during daily activities. AB - The prognostic significance of ischemic changes during daily activities was assessed in 56 patients with stable angina pectoris. All patients had positive results on the treadmill stress test and angiographic evidence of significant coronary artery disease. Forty-three (77%) had ischemic episodes on Holter monitoring during everyday activities. During the follow-up period (mean 2 years), there were 6 deaths and 6 myocardial infarctions among the 43 patients with ischemic episodes, compared with none among the 13 patients without such changes (p less than 0.03). All 14 patients referred for coronary bypass surgery belonged to the group with ischemic episodes (p less than 0.02). The extent of coronary disease, the treadmill test parameters, and the duration and frequency of ischemia during daily activities were identical in the patients with and without subsequent cardiac events. Patients with only symptomatic ischemic episodes or those with both silent and symptomatic episodes had a frequency of cardiac events similar to that of patients with only silent episodes. Thus, it seems that patients with stable angina pectoris and ischemic episodes during daily activities have a worse prognosis than patients free from such episodes. PMID- 2913730 TI - Clinical and hemodynamic effects of long-term administration of gallopamil in patients with coronary artery disease and normal or impaired left ventricular function. AB - The hemodynamic and clinical profiles of gallopamil, a new calcium antagonist, were evaluated in 20 patients with severe coronary artery disease in a placebo controlled, single-blind study. The patients were divided into 2 groups depending on baseline ejection fraction (greater than 45 or less than or equal to 45%) and underwent nuclear ventriculography, both at rest and during bicycle exercise under electrocardiographic monitoring, after 3 weeks of therapy (50 mg 3 times daily) and the 1-week run in and washout placebo periods. The mean anginal weekly frequency per patient was significantly reduced, from 3.4 to 0.5 (p less than 0.001). The left ventricular ejection fraction, cardiac volumes, ejection and filling indexes at rest and for the same workload were not altered in the population as a whole or in each of the 2 groups. The rate pressure product during exercise was reduced for the same workload from 18.0 +/- 5.0 X 10(3) to 16.8 +/- 4.7 X 10(3), while the regional ejection fraction in ischemic regions was not significantly changed. Individual variations of ventriculographic parameters in both groups were not related to basal values. Gallopamil increased the total duration of exercise from 432 +/- 201 to 537 +/- 188 s (p less than 0.001). Six patients did not complain of angina and their exercise was interrupted because of muscular weakness. The hemodynamic and clinical responses did not differ when the results in the population as a whole and in each of the 2 groups were compared. Gallopamil was effective and well tolerated, even in patients with very depressed cardiac function. PMID- 2913731 TI - Cryoablation of refractory sustained ventricular tachycardia due to coronary artery disease. AB - Thirty-nine patients with medically refractory sustained monomorphic ventricular tachycardia (VT) due to coronary artery disease underwent map-guided cryosurgery. Locations of prior myocardial infarctions had been inferior in 22, anterior in 16 and combined in 1. Mean age was 61 +/- 9 years and the mean number of drug trials per patient before surgery was 3.8 +/- 1.4. Intraoperative endocardial mapping induced 67 tachycardias in 35 patients. Each patient received 6 to 18 (11 +/- 3) endocardial cryothermic applications (15 mm, -60 degrees C, 2 minutes) at areas of earliest activation during VT. Encircling endocardial cryoablation was performed in 4 patients who had unsuccessful mapping. In addition, 11 patients had subendocardial resection of their well-demarcated septal scars as well as cryosurgery. There were 2 in-hospital deaths. At postoperative programmed ventricular stimulation, 28 of the 37 patients (76%) had no inducible or spontaneous VT before hospital discharge. Six patients (16%) with spontaneous or inducible VT had a single morphology and were controlled with antiarrhythmic drugs that had previously failed. Therefore, surgery alone or in combination with drugs was efficacious in 92% of the population surviving surgery. The remaining 3 patients (8%) received automatic implantable cardioverter defibrillators. No significant difference in surgical outcome was seen between patients who had cryosurgery alone and those who had subendocardial resection together with cryoablation. Mean left ventricular ejection fractions before and after surgery were 33 and 39%, respectively (p less than 0.01). Clinical follow-up ranged from 2 to 36 months (18 +/- 12). One patient died of heart failure and another underwent heart transplantation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2913732 TI - Bundle branch block during orthodromic reciprocating tachycardia onset in infants. AB - Transesophageal electrophysiologic studies were performed in 58 infants (age less than or equal to 1 year, median 10 days) with electrocardiographically documented orthodromic reciprocating tachycardia (ORT). The aim was to evaluate the occurrence, type and electrophysiologic effects of bundle branch block (BBB) during ORT onset. Of the 58 infants, 25 (43%) had BBB with pacing-induced tachycardia onset. BBB was initiated by single or double premature atrial extrastimuli and by burst atrial pacing; 4 infants also demonstrated BBB with spontaneous ORT onset during transesophageal study. Two of 25 infants had BBB only after intravenous procainamide. Comparison of the 25 infants exhibiting BBB at ORT onset with the 33 infants not demonstrating BBB revealed that age was not statistically different in the 2 groups, but that severity of illness (based on a 1 to 3 scale) was greater (p less than 0.05) and normal QRS ORT cycle length was shorter (p less than 0.02) in the infants with BBB. Of the 25 infants with BBB at ORT onset, 17 had left BBB, 3 had right BBB and 5 had both left and right BBB. Ventriculoatrial interval or cycle length increases during ORT with BBB in 16 of 25 (64%) infants suggested left free wall-accessory atrioventricular connections.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2913733 TI - Comparison of cardiovascular and skeletal features of primary mitral valve prolapse and Marfan syndrome. AB - The association of primary mitral valve prolapse (MVP) with thoracic bony abnormalities has led to the suggestion that MVP may be a forme fruste of the Marfan syndrome. Echocardiographic, skeletal and anthropometric findings in 59 subjects with primary MVP and 59 age- and sex-matched patients with Marfan syndrome were compared with those in 59 control subjects. Subjects with mitral prolapse were similar to control subjects and differed (p less than 0.025 to p less than 0.001) from the patients with Marfan syndrome in aortic root dimensions, height, arm span, upper/lower segment ratio and prevalences of arachnodactyly, scoliosis and pectus carinatum. Subjects with mitral prolapse and patients with Marfan syndrome had similar body mass indexes and prevalences of pectus excavatum and straight back. All 3 groups were similar in arm span/height ratio. The 5 subjects with MVP and arachnodactyly had lower weights, smaller body surface areas and smaller aortic root dimensions, and were more likely to have scoliosis than subjects with MVP without arachnodactyly. Thus, primary MVP differs from the Marfan syndrome in all major skeletal and cardiovascular features. PMID- 2913734 TI - Size of the normal aortic root in normal subjects and in those with left ventricular outflow obstruction. AB - This study establishes normal values and growth curves of the aortic root to determine when it is unusually small. The aortic root diameter was measured by 2 dimensional echocardiography in 188 normal subjects (group 1) and in 33 patients (group 2) with left ventricular outflow obstruction in whom the diagnosis of small aortic root was made during surgery for aortic root and valve replacement. In group 2 the aortic root was also measured by M-mode echocardiography and was compared to measurements during surgery. Growth curves of the normal aortic root were obtained. In group 2 the aortic root was smaller than normal except in 3 patients. When corrected for body surface area all were smaller than normal. The 2-dimensional echocardiographic and surgical measurements were almost identical. M-mode values were higher (p less than 0.01). The normal values and growth curves of the aortic root diameter are thus established and the small aortic root can be identified preoperatively. PMID- 2913735 TI - Assessment and follow-up of patients with ventricular septal defect and elevated pulmonary vascular resistance. AB - Cardiac catheterization was undertaken in 87 patients (for a total of 89 studies) with ventricular septal defects, including 58 patients with moderate or severe elevation of pulmonary arteriolar resistance. When resting resistance was less than or equal to 7.9 U . m2, it always decreased with isoproterenol and no postoperative problems were experienced with pulmonary vascular obstructive disease. In 36 patients resting resistance measured greater than or equal to 8 U . m2. In 17 of these patients it decreased to less than 7 U . m2 with isoproterenol. Fifteen patients were operated on and postoperative problems with pulmonary vascular disease were experienced only in the single patient whose repair broke down. Surgery was undertaken in 4 of 19 patients in whom resistance did not decrease to less than 7 U . m2 with isoproterenol and advanced pulmonary vascular disease was evident in the 3 patients with follow-up observation. Correlation between measured resistance and other hemodynamic parameters was only fair. A pulmonary to systemic resistance ratio greater than or equal to 0.75 always indicated high absolute resistance but resistance ratios less than 0.75 were found quite frequently in the group with limited response to isoproterenol. These data argue that a reliable estimate of resistance, less than 7 U . m2, with a vasodilator predicts a good postoperative response regardless of measurements at rest or other hemodynamic parameters. Although observations on postoperative progress of patients with resistance greater than 7 U . m2 with a vasodilator are limited, a good postoperative course is unlikely unless resistance can be lowered to a level close to 7 U . m2. PMID- 2913736 TI - Two-dimensional and Doppler echocardiographic evaluation after arterial switch repair in infancy for complete transposition of the great arteries. AB - The most recent postoperative echocardiographic examinations of all children who underwent arterial switch repair of transposition of the great arteries from August 1985 to December 1987 were reviewed. The patients included 35 children whose age at operation was 12 +/- 16 days and whose weight was 3.6 +/- 0.4 kg. Thirty-three patients are alive and well; 1 died intraoperatively and 1 died immediately postoperatively. The time of the follow-up echocardiographic examination ranged from 1 day to 2.5 years (mean 9.2 months) with 11 patients examined greater than 1 year after surgery. Complete examination of the repair site was possible in all patients. Echocardiographic visualization of distortion of the great arteries at the suture lines was seen in all patients; however, Doppler evidence of hemodynamically significant obstruction at the repair site was uncommon. On Doppler examination in the surviving 33 patients, 16 had no supravalvular pulmonary stenosis and 14 had mild to moderate supravalvular pulmonary stenosis with peak systolic pressure gradients ranging from 16 to 56 mm Hg (mean 31). Three patients had severe supravalvular pulmonary stenosis and peak systolic pressure gradients of 66, 74 and 77 mm Hg (2 have had reoperation, 1 is awaiting surgery). On Doppler examination, 4 patients had mild supravalvular aortic stenosis with peak systolic gradients ranging from 10 to 29 mm Hg. Doppler gradients were confirmed in 10 patients who had catheterization 12 +/- 3 months after surgery. Three patients had mild pulmonary regurgitation by Doppler examination, 5 had mild aortic regurgitation, 4 had mild tricuspid regurgitation and 2 had mild mitral regurgitation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2913737 TI - Noninvasive evaluation of world class athletes engaged in different modes of training. AB - This study evaluated by noninvasive methods the cardiac structure and functional characteristics of world class athletes participating in different types of training programs. Fourteen subjects, including 4 strength-trained (discus and shot put), 4 endurance-trained (long distance runners), 4 decathlon-trained (strength and endurance), 2 wheelchair athletes and 31 college-age control subjects were evaluated using electrocardiography, M-mode echocardiography and maximal oxygen consumption. M-mode echocardiography measurements of left ventricular structure and function were compared before and after normalization for lean body weight. As expected, endurance athletes had greater maximal O2 consumption than the other groups (p less than 0.05). Before normalization for lean body weight, there were no significant differences in end-diastolic dimensions. After normalization, the endurance, wheelchair and control subjects had end-diastolic dimensions larger than those of strength athletes. Strength athletes appeared to have a much larger posterior wall and septal thickness than all groups except the decathlon athletes. However, when normalized, there was no difference among any of the groups. Previous investigators have attempted to determine "normalcy" of cardiac hypertrophy by looking at the ratio of left ventricular wall thickness to left ventricular radius. In the present study, the thickness to radius ratio in strength athletes was 33% greater than that in endurance athletes. It appears that the left ventricular wall thickness in the strength athletes occurred without a concomitant increase in left ventricular radius and that the left ventricular hypertrophy of world class athletes is related to the total increase in lean body weight. However, ventricular dimensions may be related more to the type of overload experienced. PMID- 2913738 TI - Cardiovascular risk factors and graded treadmill exercise endurance in healthy adults: The Framingham Offspring Study. AB - To help describe the association between exercise endurance and cardiovascular risk factor profiles, 2,606 young and middle-aged healthy adults in the Framingham Offspring Study were given submaximal treadmill tests. For both men and women, exercise endurance was inversely related to resting heart rate (p less than 0.001), body mass index (p less than 0.001), systolic blood pressure (p less than 0.001) and blood glucose (p less than 0.01), and positively related to high density lipoprotein (HDL) cholesterol (p less than 0.05). In men, cigarette smoking (p less than 0.05), high levels of total cholesterol (p less than 0.01) and very low density lipoprotein (VLDL) cholesterol (p less than 0.001) were also associated with poor exercise endurance. After adjusting for age, resting heart rate and body mass index, significant independent associations persisted for HDL cholesterol (p less than 0.05) in both sexes and for systolic blood pressure, VLDL cholesterol, blood glucose and cigarette smoking in men (p less than 0.05). Risk factors associated with overt cardiovascular disease in older individuals are also associated with poor exercise endurance in those who are younger and asymptomatic. PMID- 2913739 TI - Left ventricular aneurysm and prognosis after first anterior wall acute myocardial infarction. PMID- 2913740 TI - Acute myocardial infarction during Holter recording. PMID- 2913741 TI - Resting left ventricular ejection fraction in elderly patients without evidence of heart disease. PMID- 2913742 TI - Frequency of mitral valve prolapse in systemic lupus erythematosus, progressive systemic sclerosis and mixed connective tissue disease. PMID- 2913743 TI - Prophylactic aspirin use among US physicians. PMID- 2913744 TI - Sudden death immediately after a record-setting athletic performance. PMID- 2913745 TI - Complete heart block during retrograde left-sided cardiac catheterization. PMID- 2913746 TI - Angiographic evidence of cardiac ventricular diastolic suction. PMID- 2913747 TI - Variant angina in two brothers with left anterior descending coronary arterial spasm. PMID- 2913748 TI - Compound pulsus alternans: independent alternation within weak beats. PMID- 2913749 TI - Effect of pregnancy on pressure gradient in mitral stenosis. PMID- 2913750 TI - Cardiac-compressing intrapericardial teratoma at birth. PMID- 2913751 TI - Cardiac resuscitation using emergency aortic balloon valvuloplasty. PMID- 2913752 TI - Use of emergency balloon dilation to reverse acute hemodynamic decompensation developing during diagnostic catheterization for aortic stenosis (bailout valvuloplasty). PMID- 2913753 TI - A simple method of differentiating between atrial septal defect and patent foramen ovale. PMID- 2913754 TI - Correlation, causation and agreement. PMID- 2913755 TI - A symposium: Acute blood pressure elevation and the brain. April 7, 1988, Leuven, Belgium. Proceedings. PMID- 2913756 TI - Arterial hypertension in neurosurgical emergencies. AB - The Cushing, or ischemic response, is a useful mechanism in intracranial hypertension because it restores normal cerebral perfusion pressure and cerebral circulation. In patients with acute intracranial hypertension due to mass expanding lesions such as brain edema, hydrocephalus or brain tumor, cerebral perfusion pressure decreases and plateau waves occur. In experimental animals, spontaneous or induced arterial hypertension can compensate for the reduction of cerebral perfusion pressure. The interrelation between arterial pressure, intracranial pressure and cerebral perfusion pressure in an experimental model of hydrocephalus in dogs was investigated. Plateau waves were preceded by a decrease in cerebral perfusion pressure and a Cushing response was seen 5 to 15 seconds before abolition of the wave. Arterial hypertension, induced by intravenous infusion of Aramin, restored cerebral perfusion pressure and intracranial pressure became normal. Arterial hypertension appears to be an efficient stimulus to abort plateau waves. Hypertensive patients in whom subarachnoid bleeding develops from ruptured aneurysm are at high risk of bleeding again and need antihypertensive treatment together with drainage of cerebrospinal fluid. Induced arterial hypertension is the most effective treatment of vasospasm but increases the danger of aneurysmal rebleeding and can only be safe after clipping of the aneurysm. This is one of the strongest arguments for early operation on cerebral aneurysms. PMID- 2913757 TI - How should we treat a hypertensive emergency? AB - Hypertensive emergencies are life-threatening situations caused by acute blood pressure elevation. They require immediate treatment with antihypertensive drugs. Such emergencies include hypertensive crisis, acute left ventricular heart failure or intracranial bleeding in patients with hypertension, malignant hypertension resistant to treatment, and serious blood pressure elevations after vascular surgery. A hypertensive crisis may be defined as a sudden increase in systolic and diastolic blood pressure that causes functional disturbances of the central nervous system, the heart or the kidneys. In patients with hypertensive crisis, treatment should be started with an alpha receptor-blocking agent if pheochromocytoma has not been excluded by previous workup. Antihypertensive agents with a rapid onset of action--nifedipine, clonidine, dihydralazine, diazoxide and sodium nitroprusside--are being used. PMID- 2913758 TI - Primary lymph node presentation of angiocentric lymphoma associated with features of a hemophagocytic syndrome. AB - The spectrum of post-thymic T-cell neoplasia includes the angiocentric immunoproliferative lesions, a group of disorders histologically exhibiting vascular infiltration and destruction; included among these disorders is angiocentric lymphoma. In contrast to the typical extranodal presentation seen in the angiocentric immunoproliferative lesions, this report describes a case of angiocentric lymphoma presenting as primary lymph node disease with clinicopathologic findings mimicking a hemophagocytic syndrome. Rearrangement of the T-cell receptor beta chain documents this case to be a clonal T-cell neoplasm. The association of this distinct histologic type of T-cell malignancy with hemophagocytic syndromes is reviewed. PMID- 2913759 TI - Apparent response of refractory post-transfusion purpura to splenectomy. AB - Post transfusion purpura (PTP) is a rare disorder characterized by the abrupt onset of severe thrombocytopenia following transfusion. A patient with PTP and massive bleeding was refractory to corticosteroids, gamma globulin, and plasma exchange but developed an immediate and sustained rise in platelet count following splenectomy. Splenectomy may be a useful therapeutic modality in patients with refractory PTP. PMID- 2913760 TI - Antileukemic effect of nitrous oxide in a patient with chronic myelogenous leukemia. PMID- 2913761 TI - Sex practice correlates of human immunodeficiency virus transmission and acquired immunodeficiency syndrome incidence in heterosexual partners and offspring of U.S. hemophilic men. AB - We assessed the risk of human immunodeficiency virus (HIV) transmission from heterosexual seropositive hemophilic men to their female sex partners through an HIV serosurvey and questionnaire study conducted during 1984-1987. Five percent of 21 female partners of asymptomatic men and 11% of 35 partners of HIV symptomatic (acquired immunodeficiency syndrome [AIDS], AIDS-related complex [ARC], peripheral generalized lymphadenopathy [PGL]) hemophilic men had been infected when first tested. One of 19 seronegative women tested about 1 year later reportedly seroconverted. Only 18% of a sample of the serosurvey women responding to sex practices questions said their partners used condoms "nearly always." Over 60% engaged in oral/genital sex in addition to vaginal intercourse. Only 12% of still-seronegative women followed the preventive strategy of consistent avoidance of oral/genital sex, together with consistent condom use by the male partner. Further evidence for heterosexual transmission comes from the CDC national AIDS surveillance reports showing 25 women who acquired HIV infection through heterosexual contact with U.S. hemophilic men (September 6, 1988). Seven (28%) were diagnosed and reported in the first 6 months of 1988. Their ages range from 20 years to more than 70 years. The dates of infection for the women are unknown but must have been at least 5 years before AIDS diagnosis for at least one. Only approximately 30% of their male partners had already manifested any HIV-associated illness. Through May 18, 1988, six cases of AIDS have occurred in children whose infection was acquired through exposure of the mother to a hemophilic partner. Four were diagnosed in latter 1987. The median age at diagnosis was 4.5 months. Four had died. None of their mothers is as yet diagnosed. PMID- 2913762 TI - Erythrocyte enzyme activities in myelodysplastic syndromes: elevated pyruvate kinase activity. AB - The erythrocyte enzyme activities in twenty-six cases of myelodysplastic syndromes were determined. There were remarkably abnormal levels in seven cases; namely, four cases showed increased hexokinase activity, three cases showed increased pyruvate kinase activity, and two cases showed increased adenosine deaminase activity. Among these, one case with elevated pyruvate kinase activity showed the novel expression of M2-type pyruvate kinase activity, in addition to the R-type pyruvate kinase activity normally found in erythrocytes. Southern blotting of peripheral leucocyte DNA revealed only an amplified PK-LR genome, which derived from the chromosomal abnormality of a 1;7 translocation. The mechanism responsible for switching M2-type to R-type during erythroid maturation was considered to be partially disrupted in this case. PMID- 2913763 TI - Blood pressure reduction and coronary heart disease risk factor management: a conjoint approach. New York, New York, June 22, 1988. Proceedings. PMID- 2913764 TI - Importance of coronary heart disease risk factors in the management of hypertension. An overview. PMID- 2913765 TI - Effect of atenolol or prazosin on maximal exercise performance in hypertensive joggers. AB - We evaluated maximal performance during cycle ergometry and treadmill exercise in 14 hypertensive male joggers treated with prazosin or atenolol in an unblinded, placebo-controlled, crossover design. Maximal oxygen uptake was measured during both exercise modalities; cardiac output was measured only during cycle ergometry using the acetylene rebreathing technique. Both drugs reduced resting systolic and diastolic blood pressures. Prazosin reduced total peripheral resistance during submaximal exercise but had little effect on maximal cycle and treadmill performance. Atenolol, in contrast, reduced treadmill duration, maximal oxygen uptake, and heart rate compared with placebo. Atenolol also increased stroke volume and the arterial venous oxygen difference and reduced cardiac output during cycle exercise. Both drugs produced similar reductions in exercise diastolic pressure, but exercise systolic pressure was lower only during atenolol treatment. Prazosin was better tolerated by the subjects and was preferred by 10 of the men. We conclude that both drugs effectively reduced resting blood pressure, but that atenolol decreased exercise cardiac output and may impede exercise performance in physically active hypertensive subjects. PMID- 2913766 TI - Comparative effects of prazosin and hydrochlorothiazide on sexual function in hypertensive men. AB - Evidence suggests that there may be differences in the incidence of drug-induced sexual dysfunction among the antihypertensive agents. This study assessed objective and subjective aspects of sexual dysfunction in hypertensive male patients in relation to two antihypertensive agents--prazosin and hydrochlorothiazide. A total of 12 hypertensive patients were evaluated in a crossover study utilizing a sleep laboratory to obtain polysomnographic evaluations of sleep patterns along with changes in nocturnal penile tumescence and buckling pressure. Objectively, no significant changes were observed between the two antihypertensive agents in relation to rapid eye movement-related sleep architecture, serum testosterone levels, or penile blood flow. Decrements in buckling pressure and subjective aspects of sexual dysfunction were greater during hydrochlorothiazide treatment than during prazosin treatment. Both drugs were effective in controlling blood pressure. PMID- 2913767 TI - Treatment strategies: an evaluation of antihypertensive therapy. PMID- 2913769 TI - Effect of alpha- and selective beta-blockade for hypertension control on plasma lipoproteins, apoproteins, lipoprotein subclasses, and postprandial lipemia. AB - Fourteen male patients (mean age +/- SD, 52 +/- 11 years) with a history of hypertension (systolic blood pressure, 148 +/- 10 mm Hg; diastolic blood pressure, 99 +/- 2 mm Hg) were enrolled in a cross-over trial of prazosin and atenolol, with a minimum of eight weeks of treatment with each drug. Measures of lipoprotein metabolism included levels of: total plasma cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and high-density lipoprotein2 cholesterol. Lipoprotein mass was measured by analytical ultracentrifugation in low-density to very low-density lipoprotein flotation rate intervals of 0 to 12, 12 to 20, and 20 to 400, and high-density lipoprotein flotation rate intervals of 0 to 3.5 and 3.5 to 9.0. Apolipoproteins A1 and B, postheparin lipoprotein and hepatic lipase activities, and magnitude of postprandial lipemia also were determined. Mass of intermediate density lipoproteins (flotation rate, 12 to 20) was significantly lower (p = 0.05) following prazosin therapy compared with atenolol therapy. Other lipid parameters, including triglycerides and low- and high-density lipoprotein cholesterol, were not significantly different for the two drug treatments. PMID- 2913768 TI - Effects of prazosin on hemodynamics, hemostasis, and serum lipid and lipoprotein levels in normal and hypercholesterolemic monkeys. AB - The effect of prazosin on hemodynamics, hemostasis, and serum lipid and lipoprotein levels was investigated in normal and hypercholesterolemic rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) monkeys. Administration of prazosin (2 mg/kg bodyweight, orally, twice a day) for three weeks caused significant reductions in plasma cholesterol, including low- plus very low density lipoprotein cholesterol, apolipoprotein B, and triglyceride levels. Drug therapy was associated with increased high-density lipoprotein cholesterol levels, although in one group of monkeys this rise also was associated with a reduction in apolipoprotein A1. Prazosin treatment significantly decreased mean arterial pressure in normal and hypercholesterolemic monkeys. As was expected, acute administration of phenylephrine caused mean arterial pressure to rise, with animals receiving normal- or high-cholesterol-containing diets showing similar responses. After prazosin treatment, however, a greater inhibition in the phenylephrine pressor response was observed in hypercholesterolemic monkeys compared with normal animals. Platelet aggregation in response to adenosine 5' diphosphate, prothrombin time, and activated partial thromboplastin time were not altered by prazosin. Thus, in our nonhuman primate models of hypercholesterolemia, administration of prazosin resulted in reduction in lipid and apoprotein levels with no change in hemostasis. PMID- 2913771 TI - Effects of antihypertensive agents on serum lipids and lipoproteins. PMID- 2913770 TI - Comparative effects of prazosin and propranolol on blood lipid profiles in hypertensive, hypercholesterolemic patients. Preliminary results. AB - Preliminary results are presented for the first 13 patients to complete an ongoing crossover study comparing the effects of prazosin and propranolol on blood pressure control, in which blood lipid profiles were monitored. The study population consisted predominantly of white men (mean age, 67.5 years) with mild to-moderate hypertension and coexisting hypercholesterolemia (mean plasma cholesterol level, 244 mg/dl). Both agents resulted in statistically significant reductions in diastolic blood pressure. It is recognized that with prazosin use, there are generally no adverse changes noted between pre- and post-treatment lipid levels. The results of this study demonstrated a 243.5 mg/dl total cholesterol level at baseline and 229.5 mg/dl maintenance levels following prazosin treatment. In contrast, the results following propranolol treatment showed a tendency to increase plasma levels of triglycerides and very low-density lipoprotein cholesterol, and to reduce levels of high-density lipoprotein cholesterol and high-density lipoprotein2 cholesterol. Because of a great deal of variability in lipid responsiveness to the study drug, none of the above changes attained statistical significance. Additional data from this ongoing study are required to confirm these preliminary observations. PMID- 2913772 TI - Interaction of diabetes with hypertension and lipids--patients at high risk. An overview. PMID- 2913773 TI - Forearm and finger hemodynamics, blood pressure control, and lipid changes in diabetic hypertensive patients treated with atenolol and prazosin. A brief report. AB - Hypertension and diabetes mellitus frequently coexist and are independent risk factors for reduced peripheral perfusion. Antihypertensive medications that reduce blood pressure and improve peripheral perfusion would have advantages in diabetic hypertensive patients. In a randomized, two-placebo-period, single blind, two-way, crossover study, finger and forearm blood flow, lipid levels, and blood pressure control were determined in 19 diabetic hypertensive patients given prazosin and atenolol, with each drug and placebo period lasting four weeks. Both drugs reduced blood pressure (sitting, 157/95 to 142/84 mm Hg for atenolol and 155/95 to 138/82 mm Hg for prazosin; standing, 154/94 to 144/84 mm Hg for atenolol and 154/94 to 133/81 mm Hg for prazosin). Lipid levels did not change, except that low-density lipoprotein levels decreased from 148 to 127 mg/dl with prazosin. Atenolol did not change forearm or finger blood flow or vascular resistance. Prazosin increased blood flow and reduced vascular resistance in both finger and forearm. In conclusion, prazosin demonstrated a potentially more appropriate hemodynamic profile than atenolol in diabetic hypertensive patients in this study. PMID- 2913774 TI - Effects of prazosin on blood pressure and diabetic control in patients with type II diabetes mellitus and mild essential hypertension. AB - The effects of prazosin treatment on blood pressure and diabetic control were assessed in 22 patients with stable non-insulin-dependent diabetes mellitus and hypertension. After an initial six-week baseline period, patients were titrated to optimal therapeutic doses of prazosin (mean daily dose, 12.9 +/- 6.5 mg). Both sitting and standing systolic and diastolic blood pressures were significantly decreased (p = 0.01) with prazosin therapy from a mean of 152/99 mm Hg sitting and 144/99 mm Hg standing to a mean of 139/84 mm Hg and 133/85 mm Hg, respectively, at the end of titration and throughout the 12-week prazosin maintenance therapy period. Seventy-seven percent of patients achieved the goal sitting diastolic blood pressure of 85 mm Hg or less. Total cholesterol, high density lipoprotein cholesterol, and triglyceride levels were not significantly altered during prazosin therapy compared with baseline measurements. Diabetic control and renal function were maintained during prazosin treatment with no significant changes from baseline noted. No unexpected adverse experiences were reported. In summary, prazosin treatment effectively reduced blood pressure without compromising diabetic control or renal function in this group of hypertensive patients with concomitant diabetes mellitus. PMID- 2913775 TI - Assessment of the effects of alpha- and beta-blockade in hypertensive patients who smoke cigarettes. AB - A 24-week, crossover, comparison study was conducted to observe the effects of alpha-blockade with prazosin and beta-blockade with propranolol on blood pressure and plasma lipoprotein levels in 15 hypertensive cigarette smokers. Before treatment, mean sitting blood pressure was 140/100 mm Hg and rose to 147/105 mm Hg after the patients smoked two cigarettes. Treatment with prazosin and propranolol lowered sitting blood pressure to 127/89 mm Hg and 129/91 mm Hg, respectively (not significant), and did not alter the pressor response to smoking. The total cholesterol level at baseline was 207.3 +/- 11.0 mg/dl. This increased to 210.5 +/- 10.2 mg/dl with propranolol treatment and decreased to 201.0 +/- 11.1 mg/dl with prazosin treatment. The low-density lipoprotein cholesterol level was 132.5 +/- 8.1 mg/dl at baseline, 136.9 +/- 8.3 mg/dl with propranolol treatment, and 129.4 +/- 9.0 mg/dl with prazosin treatment (0.05 less than p less than 0.10 between-group comparison). The data indicated that whereas prazosin and propranolol are equally effective in controlling blood pressure in hypertensive cigarette smokers, effects on plasma lipoproteins also may need to be considered when selecting a first-step antihypertensive agent in this coronary prone population. PMID- 2913776 TI - The long-term antihypertensive effects of prazosin and atenolol. AB - The efficacy and tolerability of the alpha-blocker prazosin was compared with that of atenolol, a beta-blocker, in the long-term treatment of uncomplicated, essential hypertension. Twelve patients were randomly assigned to prazosin treatment and 15 to treatment with atenolol. Drug therapy was titrated to reduce diastolic blood pressure by 10 mm Hg or to below 89 mm Hg, whichever was lower. If monotherapy with either study drug failed to do this, hydrochlorothiazide was added to the regimen. Once blood pressure control was established, patients received maintenance therapy at that dosage and were followed for up to 12 months. Blood pressure, side effects, and plasma lipid levels were monitored during this period. Seventy-five percent of patients receiving prazosin monotherapy attained blood pressure goals, compared with 60 percent of patients given atenolol monotherapy. With the addition of low-dose hydrochlorothiazide, those patients not having an adequate response to monotherapy attained blood pressure control. Blood pressure reductions were maintained without dosage adjustment throughout the maintenance period; patient acceptance was good, and there was no evidence of tolerance. Treatment with atenolol produced slight increases in plasma triglyceride levels and little change in total or low-density lipoprotein cholesterol. In contrast, patients treated with prazosin demonstrated no adverse effects with regard to lipid levels. Although a higher percentage of patients reached goal blood pressure with prazosin monotherapy than with atenolol, the response rates were comparable when hydrochlorothiazide was added to the regimens. PMID- 2913777 TI - Prazosin in hypertensive patients with chronic bronchitis and asthma: a brief report. AB - The effects of prazosin therapy were recently evaluated in ambulatory patients with essential hypertension and chronic obstructive pulmonary disease. Both the ability of prazosin to control high blood pressure and its effects on pulmonary function were observed. Systolic and diastolic blood pressures were significantly reduced at the end of the maintenance period. Of the 17 patients completing the trial, 82.4 percent attained a target diastolic blood pressure of less than 90 mm Hg, and 70.6 percent attained a diastolic reduction of greater than 10 mm Hg. Results of six-hour pulmonary function tests showed no significant differences after dosing with placebo or with prazosin. There was a significant increase in the number of patients who noted increased wheezing, but these patients did not have any increase in cough or sputum symptoms. PMID- 2913778 TI - Lowering blood pressure in patients without affecting quality of life. PMID- 2913779 TI - Effects of antihypertensive therapy on blood pressure control, cognition, and reactivity. A placebo-controlled comparison of prazosin, propranolol, and hydrochlorothiazide. AB - A randomized, placebo-controlled trial was conducted to compare the effects of treatment with prazosin, propranolol, or hydrochlorothiazide on the following variables: blood pressure, cognitive and psychomotor skills, cardiovascular reactivity to natural and laboratory challenges, and serum lipid and lipoprotein levels. Side effects were recorded and patients evaluated how they felt during their treatment. Sixty-nine men, 35 percent black, aged 25 to 55 (mean 51.3) years, with diastolic blood pressures between 90 and 104 mm Hg (mean, 93.3 mm Hg), completed the study. There were no differences between active treatment groups in the proportion of patients with controlled blood pressure during the maintenance phase of the study. In the cognitive and psychomotor tests, the hydrochlorothiazide group showed significantly less improvement from baseline than the other treatment groups on the block design subscale of the Wechsler Adult Intelligence Scale-Revised, and there was a trend for the propranolol group to have less improvement from baseline than the other groups on the digit span subscale. There were no other significant pretreatment to post-treatment changes in the other cognitive or psychomotor tests, the Russell Revision of the Wechsler Memory Scale, or a number of computerized reaction-time and signal-detection tasks. In the reactivity testing, there was a significantly lower increase in heart rate in the prazosin group compared with placebo during the second laboratory challenge of the Stroop Color Interference Test. Post-treatment declines in ambulatory blood pressure were seen in all of the drug treatment groups in average and maximal diastolic and systolic blood pressures. Both propranolol and hydrochlorothiazide treatment resulted in low-density lipoprotein cholesterol levels that were higher than baseline and the hydrochlorothiazide treatment had significantly increased total cholesterol levels. In contrast, the prazosin-treated group experienced no adverse changes in these parameters. Overall, the propranolol group had significantly more moderate and severe side effects than did the other three groups. Considering the pattern of blood pressure control, cognitive and psychomotor effects, changes in lipid levels, and magnitude of side effects, prazosin seems to have the most advantageous profile in this study of the three anti-hypertensive agents evaluated. PMID- 2913780 TI - Should the elderly be resuscitated following out-of-hospital cardiac arrest? Why not? PMID- 2913781 TI - Should the elderly be resuscitated following out-of-hospital cardiac arrest? AB - PURPOSE: Elderly and younger patients who were successfully resuscitated and hospitalized following out-of-hospital cardiac arrest were studied to determine if there was a significant difference in hospital course and long-term survival between the two groups. PATIENTS AND METHODS: The study consisted of 214 consecutive patients, divided into two age groups: elderly (more than 70 years, n = 112) and younger (less than 70 years, n = 102). Hospital charts and paramedic run data were retrospectively reviewed for each patient and findings were compared between the two age groups. RESULTS: Prior to cardiac arrest, 47 of 112 (42 percent) elderly patients had a history of heart failure, compared with 19 of 102 (18 percent) younger patients, and were more commonly taking digitalis (51 percent versus 29 percent) and diuretics (47 percent versus 26 percent). Younger patients, however, more often had an acute myocardial infarction at the time of the cardiac arrest (33 percent versus 16 percent). At the time of cardiac arrest, 83 percent of younger patients demonstrated ventricular fibrillation, compared with 71 percent of the elderly. In contrast, electromechanical dissociation was five times more common in the elderly patients. Although hospital deaths were more common in the elderly (71 percent versus 53 percent), the length of hospitalization and stay in intensive care units were not significantly different between the age groups. The number of neurologic deaths was similar in both age groups, as were residual neurologic impairments. Only five elderly patients and six younger patients required placement in extended-care facilities. Calculated long-term survival curves demonstrated similar survival in both age groups, with approximately 65 percent of hospital survivors alive at 24 months after hospital discharge. CONCLUSION: Resuscitation of elderly patients in whom out-of-hospital cardiac arrest occurs is reasonable and appropriate, according to the findings of this study. Even though elderly patients are more likely than younger patients to die during hospitalization, the hospital stay of the elderly is not longer, the elderly do not have more residual neurologic impairments, and survival after hospital discharge is similar to that in younger patients. PMID- 2913782 TI - Delayed diagnosis of gynecologic tumors in elderly women: relation to national medical practice patterns. AB - PURPOSE: To evaluate the hypothesis that less aggressive cancer screening practices might result in later diagnosis of cancer in the elderly, we analyzed the stage of diagnosis of tumors by age in the Connecticut Tumor Registry. PATIENTS AND METHODS: Using Registry data from 1960 to 1975 and 1976 to 1983, we compared the proportion of tumors that were diagnosed at a localized stage among white women of various age groups. Thirteen specific tumor sites were analyzed, accounting for 55,688 tumors between 1960 and 1975 and 38,715 tumors between 1976 and 1983. RESULTS: Only gynecologic cancers demonstrated a significant inverse relationship between the relative proportion of tumors that were diagnosed at a localized stage and advancing patient age during both time periods. Specifically, when the youngest women (aged 25 to 34) were compared with the oldest women (aged 85 and over), between 1960 and 1975, the relative proportion of localized cervical, uterine, and ovarian cancer dropped from 98 percent to 59 percent, 92 percent to 77 percent, and 59 percent to 27 percent, respectively. Similar declines were also seen between the intermediate-age groups, and data from 1976 to 1983 demonstrated identical age-related trends. CONCLUSION: Our study reveals that the probability of diagnosing cancer of the cervix, uterus and ovaries at a localized and potentially curable stage decreases with advancing age. Published national health practice patterns demonstrated a similar age-related decline in gynecologic examinations and Pap smears even after adjustment for the exclusion of women who would have undergone previous hysterectomy. This decreasing use of gynecologic examinations may in part explain the age-related decline in localized gynecologic cancers. PMID- 2913783 TI - Occult polymicrobial endocarditis with Haemophilus parainfluenzae in intravenous drug abusers. AB - PURPOSE AND PATIENTS AND METHODS: Fewer than 8 percent of intravenous drug abusers are found to have polymicrobial endocarditis. We report on cases of occult polymicrobial infective endocarditis with Haemophilus parainfluenzae in 10 intravenous drug abusers. Clinical and laboratory data on all 10 patients were obtained from hospital charts, and information on illicit drug use methods was given by five patients. Blood cultures were performed, as well as susceptibility testing to antibiotics. Subsequent molecular epidemiologic studies were performed on selected Staphylococcus aureus and H. parainfluenzae strains. Phage typing of S. aureus and biotyping of H. parainfluenzae strains were also done. RESULTS: Results of the initial blood cultures were positive on the second to fifth days (mean, 2.6 days), demonstrating a gram-positive pathogen in nine patients and Bacteroides asaccharolyticus in one. Significantly, in each case, H. parainfluenzae alone was subsequently identified from additional blood cultures, with a mean delay of 20.4 days (range, five to 57 days) to the isolation of this organism. Epidemiologic data indicated that our cases did not represent a point source outbreak. Antibiotic therapy uniformly failed until an agent active against H. parainfluenzae was added. The constellation of clinical, microbiologic, and epidemiologic findings was similar, and permitted prospective diagnosis and therapy in three patients. Despite the absence of S. aureus bacteremia in four, all 10 patients had right-sided endocarditis with septic pulmonary emboli. Five patients had initial blood cultures that were positive for two facultative gram-positive cocci (S. aureus and commensal oral streptococcal species). CONCLUSION: Our findings suggest that polymicrobial endocarditis with H. parainfluenzae in intravenous drug abusers is a distinct clinical syndrome, and should be considered in all patients if the response to appropriate antibiotics is atypical or if pulmonary emboli continue with therapy. PMID- 2913784 TI - Cocaine-associated acute myoglobinuric renal failure. AB - PURPOSE: Abuse of cocaine is associated with serious medical complications involving the heart, central nervous system, and gastrointestinal tract. Renal complications appear to be uncommon. We describe herein four patients with rhabdomyolysis and acute myoglobinuric renal failure temporally related to cocaine use. CASE REPORTS: Acute cocaine intoxication was the most common presentation and rhabdomyolysis was an unexpected finding. Renal failure progressed rapidly in all patients, necessitating dialysis in two. The prognosis was good, and all patients survived. The mechanism of cocaine injury is unclear; possibilities include increased muscle activity, muscle compression, hyperthermia, and vasospasm with muscle ischemia. CONCLUSION: Rhabdomyolysis with acute renal failure should be recognized as a possible complication of cocaine abuse. PMID- 2913785 TI - A question of velleity. PMID- 2913786 TI - Migratory polyarthritis, pulmonary nodules, and chest pain in a 60-year-old man. PMID- 2913787 TI - Unsuspected Cushing's disease in a patient with fatal staphylococcal bacteremia and multiple pituitary adenomas. PMID- 2913788 TI - Celiac axis compression syndrome caused by sarcoidosis: an acquired form of the syndrome. PMID- 2913789 TI - Mild sickle cell anemia associated with alpha globin mutant alpha Montgomery. PMID- 2913790 TI - Unusual longevity in primary systemic amyloidosis: a 19-year survivor. PMID- 2913791 TI - Streptokinase and splenic rupture. PMID- 2913792 TI - Unilateral hyperlucent lung due to interstitial pulmonary hemorrhage from aortic dissection. PMID- 2913793 TI - Yersinia enterocolitica bacteremia in a patient with the acquired immunodeficiency syndrome. PMID- 2913794 TI - Priapism following testosterone administration for delayed male puberty. PMID- 2913795 TI - Recurrent bacteremia in a university hospital. PMID- 2913796 TI - Generation of reactive metabolites during spontaneous degradation of atracurium in vitro. AB - The hypothesis was tested in vitro that the spontaneous degradation of atracurium leads to formation of electrophilic metabolites. Variable amounts of atracurium were incubated in saline (0.9% NaCl) for 120 minutes at pH 8.0 and 37 degrees C. Subsequently, cysteine was added to the incubation solutions and the incubation was continued at pH 7.4 and 37 degrees C. Frequent determination of the mercapto groups of cysteine revealed a progressive diminution of the mercapto groups remaining in the incubation solutions. The consumption of sulfhydryl groups was maximal at 20 minutes after the addition of cysteine and amounted to approximately twice the molar amount of atracurium. Kinetic analysis indicated that one mercapto group was consumed almost instantly, whereas the consumption of the other proceeded with a half-life of 4 minutes. No consumption of mercapto groups was observed when laudanosine was incubated with cysteine. Incubation of atracurium or of its degradation products with carboxylesterase markedly reduced the amount of reactive metabolites present in the incubation solutions. The results are compatible with the working hypothesis that spontaneous degradation of atracurium via Hofmann elimination results in generation of two equivalents of reactive electrophilic esters, probably acrylates. We propose that in vivo the portion of the aliphatic chain in the atracurium molecule that is converted to acrylates by Hofmann elimination may be eliminated in part in urine as a conjugate of mercapturic acid. PMID- 2913798 TI - Allocating research space in the university medical center: use of a mathematical formula. AB - Allocation of research space often is one of the most emotional and contentious issues facing a university medical center. With decreasing dollars available for building new research laboratories in medical schools, the assignment of laboratory space to basic science and clinical departments presents a difficult problem for deans, chairmen, and faculty. In this article, the authors outline a formula in which net square feet of traditional research space (ie, wet-bench laboratories) may be allocated on the basis of research dollars, output of manuscripts and abstracts averaged over 3 years, and the number of personnel who will use the space. Caution is urged for arbitrarily applying a space formula when it does not apply, ie, nontraditional research, and when insufficient consideration has been given to the individual case. The formula is most useful when applied within a specific institution and primarily for comparative purposes. Nonetheless, once the formula is established, it provides an objective mechanism by which the need for space and the relative merits of space assignments within a department or among departments can be more effectively determined and managed. PMID- 2913797 TI - Recovery of thyroid function in primary hypothyroidism. AB - In recent years transient primary hypothyroidism has reported with increasing frequency. Physicians are often unsure whether withdrawal of thyroid hormone to identify the transient hypothyroidism is indicated and cost-effective and in which patients this should be done. To study these questions, thyroid hormone therapy was withdrawn from 63 patients with proven primary hypothyroidism at 6 months and again at 1 and 3 years to determine if there was recovery of thyroid function. Of the 49 patients with primary hypothyroidism (PH) that was not attributable to such causes as drug therapy, surgery, iodine-131 therapy, or silent or subacute thyroiditis, only two patients recovered thyroid function. In the other 14 patients, hypothyroidism developed within 6 months postpartum. Nine of these 14 recovered thyroid function. Therefore, it appears that when PH is not related to certain specific causes or states, it is likely to be permanent. Furthermore, withdrawal of thyroid hormone therapy to assess recovery of thyroid function is unnecessary and not cost-effective. PMID- 2913799 TI - Gallium-67 uptake by the thyroid associated with progressive systemic sclerosis. AB - Although thyroidal uptake of gallium-67 has been described in several thyroid disorders, gallium-67 scanning is not commonly used in the evaluation of thyroid disease. Thyroidal gallium-67 uptake has been reported to occur frequently with subacute thyroiditis, anaplastic thyroid carcinoma, and thyroid lymphoma, and occasionally with Hashimoto's thyroiditis and follicular thyroid carcinoma. A patient is described with progressive systemic sclerosis who, while being scanned for possible active pulmonary involvement, was found incidentally to have abnormal gallium-67 uptake only in the thyroid gland. Fine needle aspiration cytology of the thyroid revealed Hashimoto's thyroiditis. Although Hashimoto's thyroiditis occurs with increased frequency in patients with progressive systemic sclerosis, thyroidal uptake of gallium-67 associated with progressive systemic sclerosis has not, to our knowledge, been previously described. Since aggressive thyroid malignancies frequently are imaged by gallium-67 scintigraphy, fine needle aspiration cytology of the thyroid often is essential in the evaluation of thyroidal gallium-67 uptake. PMID- 2913800 TI - Prognosis in pyelonephritis: promise or progress? AB - Prognosis in pyelonephritis, or upper urinary tract infection, is provided. This infection is not responsible for progressive renal disease in young or elderly patients but accounts for frequent febrile episodes in women of all ages and men after the age of 50. Vigorous local immune response develops with the infection, which never succeeds in eradicating bacteria but does limit the infection and provides a diagnostic test: the antibody-coated bacteria test. Emphasis is placed on the need for a localization test for upper tract infection because studies based exclusively on clinical criteria are invalid. Appropriate therapy for mildly ill patients is given with recommendations of combination therapy for severely ill persons. Long-term follow-up is critical because most patients with recurrent infections can be given preventive therapy without subjecting them to needless urologic evaluation. PMID- 2913801 TI - Acute aluminum toxicity associated with oral citrate and aluminum-containing antacids. AB - The authors report the development of a rapidly progressive encephalopathy marked by confusion, myoclonus, seizures, coma, and death in a group of women with renal failure who received an oral solution of citrate and aluminum hydroxide gel concurrently. Two patients were documented as having marked hyperaluminemia far exceeding blood aluminum levels encountered in the chronic state of aluminum intoxication. We ascribe the toxicity to enhanced gastrointestinal absorption of aluminum when complexed with citrate. PMID- 2913802 TI - Pseudotumor cerebri induced by danazol. AB - Intracranial hypertension with papilledema occurred in two patients receiving danazol therapy for either cyclic neutropenia or immune hemolytic anemia. Results of clinical, laboratory, and neuroradiologic studies showed no apparent cause for the condition in Case 1 and the papilledema resolved one month after discontinuing danazol. Carotid angiography in Case 2 demonstrated cerebral venous sinus thrombosis; the papilledema showed gradual improvement after cessation of danazol. An additional seven cases of pseudotumor cerebri presumed secondary to danazol therapy have been reported to the Food and Drug Administration. The papilledema resolved in all seven cases soon after discontinuing danazol. A drug induced complication should be suspected, and alternative therapy sought, in patients who develop intracranial hypertension associated with administration of danazol. PMID- 2913803 TI - Orbital hemorrhage and eyelid ecchymosis in acute orbital myositis. AB - We examined two patients with acute orbital myositis associated with orbital hemorrhage and eyelid ecchymosis. Both patients were young women (aged 22 and 30 years) who had painful proptosis, diplopia, and computed tomographic evidence of single extraocular muscle involvement with spillover of inflammatory edema into the adjacent orbital fat. Patient 1 showed contralateral preseptal eyelid inflammation and did not suffer an orbital hemorrhage until after an episode of vomiting. In Patient 2, the diagnosis of occult orbital varix was initially considered but an orbital exploration and a biopsy specimen showed no vascular anomaly. Both patients were treated successfully with high-dose systemic corticosteroids. Some cases of idiopathic orbital inflammation may be related to preexisting vascular anomalies or orbital phlebitis. PMID- 2913804 TI - Effect of various doses of radiation for uveal melanoma on regression, visual acuity, complications, and survival. AB - We reviewed 284 choroidal and ciliary body melanomas treated with 50, 60, 70, or 80 gray equivalents (GyE) of helium ion radiation. Multivariate methods of data analysis were used to adjust for differences between dose groups with respect to the characteristics of patients (and their tumors). Radiation dose level did not affect survival, complications, visual outcome, or tumor regression in this model. The minimum radiation dose necessary to achieve tumor control with charged particles may be less than 50 GyE. PMID- 2913805 TI - Seven cases of trilateral retinoblastoma. AB - Of 245 consecutive children with retinoblastoma referred to the Oncology Service at the Wills Eye Hospital between January 1974 and August 1988 and followed up for three months to 15 years, seven (3%) developed midline intracranial malignancies consistent with the diagnosis of trilateral retinoblastoma. Six of the seven had bilateral retinoblastoma, and four had a family history of retinoblastoma. The time of diagnosis of retinoblastoma varied between five months after the intracranial tumor was diagnosed and four years before the intracranial tumor was diagnosed. The midline intracranial malignancies were pineal tumors (five cases), suprasellar neuroblastoma (one case), and a parasellar undifferentiated calcified mass (one case). Despite control of the intraocular tumors, five of the seven children have died of the intracranial tumors. PMID- 2913806 TI - Effect of intracameral carbachol on intraocular pressure after cataract extraction. AB - Thirty-two patients were randomly assigned to a treatment or a control group to determine the dose-response and duration of action of intracameral carbachol on immediate postoperative intraocular pressure after extracapsular cataract extraction using a viscoelastic substance. Patients in the treatment group received 0.5, 0.25, or 0.1 ml of 0.01% intracameral carbachol. Patients in the control group received 0.1 or 0.5 ml of balanced salt solution. Intraocular pressures of all patients were measured preoperatively and at three, six, 12, 24, and 48 hours postoperatively. The control group as a whole showed a 9.5-mm Hg intraocular pressure rise at three hours, a 10.0-mm Hg rise at six hours, a 9.0 mm Hg rise at 12 hours, and a 7.2-mm Hg rise at 24 hours postoperatively. The group treated with 0.5 ml of carbachol maintained stable intraocular pressures through the 48-hour measurement period. The groups treated with 0.25 and 0.1 ml of carbachol maintained stable intraocular pressures through 24 hours postoperatively. The differences in intraocular pressure were statistically significant for all treated groups through the 24-hour measurement. PMID- 2913807 TI - Pseudoglaucomatous physiologic large cups. AB - Using planimetric analysis of stereoscopic optic disk photographs, we studied 21 optic nerve heads of 11 subjects who shared the common feature of optic cups that were larger than the mean + 2 S.D. within the normal population. A comparison of these findings to those of 571 normal optic disks and 706 optic nerve heads in eyes with chronic primary open-angle glaucoma showed the following morphologic characteristics: (1) abnormally large optic disk area (mean +/- S.D., 4.49 +/- 0.56 mm2), (2) large cup/disk ratios with the horizontal ratio (0.78 +/- 0.03) significantly (P less than .001) larger that the vertical (0.71 +/- 0.03), (3) increased incidence of cilioretinal arteries, (4) normal neuroretinal rim area (2.06 +/- 0.35 mm2), (5) normal neuroretinal rim configuration, inferiorly (0.43 +/- 0.08 mm) broader (P less than .001, Wilcoxon test) than superiorly (0.33 +/- 0.06 mm), smallest (P less than .0001) temporally (0.20 +/- 0.04 mm), (6) normal form of zone alpha (irregular hypopigmentation and hyperpigmentation) of the parapapillary chorioretinal atrophy with its widest extension in the temporal horizontal area, (7) no zone beta (visible large choroidal vessels and sclera), (8) normal caliber of the parapapillary retinal vessels, and (9) normal parapillary retinal nerve fiber layer. These characteristics are helpful in the differentiation of primary and secondary large cups. PMID- 2913808 TI - Large optic disks in the Marshallese population. AB - On routine examination, asymptomatic patients from the Marshall Islands were noted to have large optic disks associated with high cup/disk ratios and normal intraocular pressure. We retrospectively analyzed color fundus photographs of 54 eyes and 22 eyes of 15 patients had optic disks greater than 2.10 mm, or megalopapilla. Of 36 patients with cup/disk ratios exceeding 0.6, 31 (86%) had visual acuities of better than or equal to 20/30. The optic nerve rim and disk areas varied directly as did disk and cup diameters. Three large disks with an 18 year photographic follow-up showed no change. Optic disk characteristics can vary widely among genetically isolated populations. PMID- 2913809 TI - Punctal occlusion and topical medications for glaucoma. AB - We studied the effects of punctal occlusion on the intraocular pressures of patients treated with topical medications for glaucoma. Silicone punctal plugs were used to occlude the inferior punctum of one eye in each of 19 patients treated with identical antiglaucoma eyedrops in both eyes. The intraocular pressures before and after punctal occlusion were compared. The eyes with the punctal plugs showed a statistically significant (P less than .0001) decrease in pressure of 1.32 mm Hg after punctal occlusion when compared to that of the fellow control unplugged eyes. The intraocular pressures in the plugged eyes decreased an average of 1.82 mm Hg after punctal occlusion when compared to before punctal occlusion (P = .001). The intraocular pressure in the unplugged control eyes did not change significantly after punctal occlusion of the fellow treated eye. PMID- 2913810 TI - Acute closed-angle glaucoma after arteriovenous fistulas. AB - Unilateral secondary acute closed-angle glaucoma was associated with a ciliochoroidal detachment in two patients. One patient, aged 17 years, had an orbital arteriovenous fistula. The other patient, aged 73 years, had a dural arteriovenous fistula that originated from branches of the right internal maxillary artery. In each patient there was increased intraocular pressure, a moderately shallow central anterior chamber, and a flat peripheral anterior chamber. The ciliochoroidal detachment was postulated to displace the iris-lens diaphragm, resulting in the closed angle. Closure of the orbital fistula in the 17-year-old patient reduced the ciliochoroidal detachment and relieved the glaucoma, but visual acuity was reduced to 20/200. The glaucoma in the 73-year old patient was relieved with topical instillation of timolol 0.5%, homatropine 5%, and systemic administration of acetazolamide. The fistula closed spontaneously, with relief of other ocular signs of the arteriovenous fistula. PMID- 2913811 TI - The management of retinal detachment complicating degenerative retinoschisis. AB - We repaired six retinal detachments complicating degenerative retinoschisis by using simultaneous external subretinal fluid drainage and intraocular gas injection without a scleral buckle or vitrectomy. The outer wall breaks were 30 to 135 degrees in size, and in three cases, extended close to the arcade vessels. We achieved retinal reattachment and collapse of the schisis cavity at surgery in all six cases. In one case, the retina redetached postoperatively, but it was repaired with a scleral buckle and gas injection. This technique simplified the management of retinal detachments complicating degenerative retinoschisis, particularly those with large or posterior outer-layer breaks. PMID- 2913812 TI - Ultrastructural studies of vitreomacular traction syndrome. AB - We performed electron microscopic studies on seven specimens removed from the posterior retina at the time of vitrectomy for vitreomacular traction syndrome. Fibrous astrocytes were the predominant cell type in all cases. Fibrocytes were present in two cases and myofibrocytes were seen in three cases. Additional cellular and extracellular features included fragments of internal limiting membrane in six cases, old collagen in all cases, new collagen in one case, occasional macrophages in four cases, and fibrous astrocytes with myofibroblastic differentiation in one case. PMID- 2913813 TI - Intraocular pressure and glaucoma. PMID- 2913814 TI - Transient comitant esotropia in a child with migraine. PMID- 2913815 TI - Previtreous space gas sequestration during pneumatic retinopexy. PMID- 2913816 TI - Incidence of corneal crystals in the monoclonal gammopathies. PMID- 2913817 TI - Capnocytophaga keratitis. PMID- 2913818 TI - Keratitis associated with disposable soft contact lenses. PMID- 2913819 TI - Spelling of anhidrosis. PMID- 2913820 TI - Management of anterior and posterior proliferative vitreoretinopathy XLV Edward Jackson memorial lecture. PMID- 2913821 TI - Incorporation of tritiated thymidine by epithelial and interstitial cells in bronchiolar-alveolar regions of asbestos-exposed rats. AB - Inhaled asbestos causes progressive interstitial lung disease. The authors have performed a series of studies to elucidate early pathogenetic events at sites of fiber deposition in asbestos-exposed rats. This study reports that a single 5 hour exposure to chrysotile asbestos induces significant increases in incorporation of tritiated thymidine (3HTdR) into nuclei of epithelial and interstitial cells of bronchiolar-alveolar regions. No cell populations in air exposed or carbonyl iron-exposed control animals exhibited more than 1% labeling at any point in time. Immediately after the 5-hour asbestos exposure, incorporation was normal. By 19 hours after exposure there was a significant increase in incorporation of 3HTdR, particularly by Type II epithelial cells of the first alveolar duct bifurcations. The greatest increase in degree of incorporation (up to 18-fold) was observed 24 hours after exposure, and increased percentages of 3HTdR-labeled cells were maintained through the 48 hours postexposure period. Normal labeling was present by 8 days after exposure, and this level remained through the 1-month period studied. This apparent mitogenic response correlates with increased numbers of bronchiolar-alveolar epithelial and interstitial cells demonstrated by ultrastructural morphometry in correlative studies. The authors speculate that the incorporation of 3HTdR could be induced by the direct effects of inhaled fibers or by mitogenic factors released from macrophages attracted to the inhaled asbestos. PMID- 2913822 TI - The clonal origin of thyroid nodules and adenomas. AB - The clonal origin of thyroid tumors in female mice heterozygous for a deficiency of the X-linked enzyme glucose-6-phosphate dehydrogenase (G6PD) was studied. Tumor phenotype was demonstrated by enzyme histochemistry. Because monophenotypia is not synonymous with monoclonality, a method to estimate the degree of mingling of the two cellular phenotypes in normal tissue was devised. Twenty-five point three percent of 624 randomly chosen pairs of adjacent follicular cells were of unlike phenotype, suggesting that if tumors were derived from 2 or more cells at least a quarter would express polyphenotypia. Four hundred fifty-three thyroid lesions induced in 20 GPDX (enzyme-deficient) mice, 20 C3H (normal) mice, and 48 heterozygous (C3HxGPDX) mice by radiation and long-term goitrogen treatment were studied. One hundred twenty-eight adenomas (sharply defined or encapsulated hypercellular lesions) were found in heterozygotes; 108 (84%) were monophenotypic, and 20 (16%) were largely monophenotypic with degenerate areas or included normal cells. None were clearly polyphenotypic. Seventy-five nodules (circumscribed but not encapsulated, largely normocellular lesion with prominent stroma) were found in heterozygotes; 25 (33%) only were monophenotypic. It is concluded that thyroid adenomas are monoclonal and nodules polyclonal. The variegated pattern of polyphenotypia in the nodules together with their prominent stromal component leads to the suggestion that there is a causative role for the stroma in their generation. PMID- 2913823 TI - Rapid fragmentation and reorganization of Golgi membranes during frustrated phagocytosis of immobile immune complexes by macrophages. AB - The authors have observed the rapid reorganization of the cellular membranes of macrophages during Fc receptor-mediated frustrated phagocytosis of immune complex coated surfaces. As the macrophages spread, large, clear basal vacuoles and anastamosing tubules were formed, occasionally contiguous with the adherent surface. Coated vesicles also were observed. This process was accompanied by a rapid reorganization of the Golgi complex region of the macrophages, which was observed using trimetaphosphatase histochemistry and an antibody to a Golgi membrane antigen as markers. On contact of the macrophages with the immune complexes, the Golgi complexes, which were tightly clustered around the centrioles, dispersed into vesicles and reorganized near the basal surface. The Golgi cisternae swelled, fragmented, and decreased in number. Golgi membrane antigen was found in the large basal vacuoles and also associated with the adherent basal surface of the macrophages. This indicates that the Golgi complexes were reorganized, in part, by a direct recruitment of their membranes to the increasing basal surface area of the spreading macrophages. The changes in the structure of the Golgi complexes were reversible; by 2 hours, the complexes had recovered their normal organization, with an accompanying decrease in the number of large basal vacuoles. These data suggest that the dynamic interrelationship among the Golgi membranes, intracellular vacuoles, and the plasma membrane can be perturbed by membrane spreading on a nonphagocytosable surface. PMID- 2913826 TI - Papillary renal cell carcinoma. A morphologic and cytogenetic study of 11 cases. AB - Most renal cell carcinomas are characterized by constant loss of the 3p13-pter chromosome segment and a frequent gain of the 5q22-qter segment. A comparative histologic and cytogenetic investigation of large series of renal cell carcinomas now shows that purely papillary tumors differ from the more common nonpapillary form not only in their morphologic characteristic, but also in karyotype changes observed. All of the 11 papillary tumors of this study failed to show any rearrangement of the critical 3p segment, and trisomy of the 5q22-qter segment has never been found. The gain of chromosome 17 was detected only in papillary renal cell carcinomas. Other nonrandom karyotype changes occurred with the same incidence in both types of tumor. Thus, some karyotype alterations in renal cell carcinomas could perhaps be regarded as a genetic mechanism responsible for the phenotype of conversed tubular cells. PMID- 2913825 TI - Immune complex-induced enteropathy. Effects of repeated injections of immune complexes on the small intestine of the rat. AB - Rats injected intravenously with immune complexes (IC) prepared in 5x antigen excess were reported previously to develop a distinctive striped pattern of serosal hyperemia of the small intestine accompanied by mucosal edema and hemorrhage. This study tested the effect of repeated injections of IC given at 3 day intervals. After the last of four, six, or nine injections, rats continued to show the same gross and histologic lesions observed in rats injected once with IC. After serial injections, however, the distal small intestine was more severely involved than the proximal intestine. In addition, villous shortening, stromal hemosiderin deposits, and gut-associated lymphoid tissue and mesenteric lymph node sinus hemorrhage and hemosiderin deposits were seen in rats given nine injections. There was a remarkable absence of stromal infiltration of the villi by inflammatory cells. Experiments conducted with 125I-labeled IC plus sufficient "cold" IC to induce intestinal lesions showed that IC were deposited at extravascular sites in the gut. The failure of such IC to provoke cellular infiltration in the gut is unexplained. PMID- 2913827 TI - Cell cycle perturbation and cell death after exposure of a human lymphoblastoid cell strain to N-methyl-N'-nitro-N-nitrosoguanidine. AB - The mechanisms involved in cell death caused by carcinogens that methylate DNA are poorly understood. In this study, the cytotoxicity of N-methyl-N'-nitro-N nitrosoguanidine (MNNG) was studied in exponentially growing T5-1 human lymphoblastoid cells. MNNG exposure killed cells and inhibited proliferation of the remaining viable cells. Reduction in cell viability, which coincided with the accumulation of cells in the late S phase of the cell cycle, was not apparent until the population had completed one doubling. Fluorescence-activated cell sorting of fluorescein diacetate-stained, MNNG-treated cells into live and dead subpopulations revealed that all cycle phases were well represented in the live fraction, whereas the dead fraction consisted primarily of cells with a sub-G1 DNA content. Thus, cell death after MNNG exposure occurred during the second cell cycle after treatment apparently as a consequence of perturbation of DNA replication and the degradation of nuclear DNA. PMID- 2913824 TI - Perturbation of the sarcolemmal membrane in isoproterenol-induced myocardial injury of the rat. Permeability and freeze-fracture studies in vivo and in vitro. AB - The mechanism whereby cardiotoxic doses of isoproterenol (ISO) induces early permeability alteration of the sarcolemmal membrane is unknown; both beta receptor overstimulation and direct toxic effect of ISO oxidation products have been implicated. There has been no morphologic observation, furthermore, on the structural basis of permeability alteration during this process. The purpose of the present study was to compare the morphology of cardiocyte injury induced by ISO and oxidized ISO (ISO-O2) and to visualize perturbation of the sarcolemma correlating with the leaky membrane. The authors studied the left ventricular myocardium of rats 10 and 60 minutes after subcutaneous administration of 85 mg/kg ISO and isolated perfused rat hearts exposed for 10 minutes either to ISO or ISO-O2 in a dose of 100 mg/l (10(-4) M) to determine the permeability of the sarcolemmal membrane using the extracellular diffusion tracer horseradish peroxidase (HRP) by light and thin section electron microscopy, the morphology of the sarcolemmal membrane by means of freeze-fracture electron microscopy, and the density of intramembrane particles (IMP) in the sarcolemmal membrane by planimetry using freeze-fracture electron microscopy. In in vivo rat hearts both 10 and 60 minutes after ISO and in vitro (isolated perfused) rat hearts exposed to either ISO or ISO-O2 for 10 minutes, HRP labeled the sarcoplasm of focally located cardiocytes implicating leakiness of the sarcolemmal membrane. HRP positive cardiocytes (with the exception of the in vivo 10 minute group) showed characteristic features of contraction band necrosis (both on light and thin section electron microscopy) in all groups. Freeze-fracture electron microscopy of sarcolemmal protoplasmic (P) membrane faces revealed two populations of cardiocytes in all groups. P-membrane faces in one population of cardiocytes appeared as in the control. In the other population of cardiocytes, P-membrane faces showed irregular tears. Planimetry demonstrated a significant decrease of IMP numerical densities in P-membrane faces with tears in the in vivo 10 minute group and both with or without tears in the in vivo 60 minutes group and the in vitro groups compared with the control values. Furthermore, with the exception of the 10 minute in vivo group, IMP densities significantly decreased in sarcolemmal membranes with tears compared with those without tears in all experimental groups. These observations are consistent with the view that catecholamine induced myocardial injury is, at least partly, related to the direct toxic effect of catecholamine oxidation products on the sarcolemmal membrane.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2913829 TI - Tobacco and health. PMID- 2913830 TI - Smoking and health: a 25-year perspective. PMID- 2913828 TI - Effects of formaldehyde on normal xenotransplanted human tracheobronchial epithelium. AB - Epithelial cells obtained from autopsies of full-term fetuses or infants less than 1 year old were isolated, amplified in primary cultures and inoculated in deepithelialized rat tracheas. These tracheas were then sealed and transplanted subcutaneously into irradiated athymic nude mice. Four weeks after transplantation the tracheal lumen was completely covered by epithelium, most of which was of mucociliary respiratory type. At this stage, tracheal transplants containing tracheobronchial epithelium from 20 different donors were exposed to silastic devices containing 0, 0.5, 1 and 2 mg paraformaldehyde. The tracheal transplants were examined histologically at 2, 4, 8, and 16 weeks after transplantation. Before sacrifice, all animals were injected with a single pulse of tritiated thymidine. Important epithelial alterations could be seen in the formaldehyde treated transplants with a maximum effect visible at 2 weeks after exposure. The highest dose of 2 mg produced, in most cases, numerous areas of epithelial erosion and inflammation whereas this effect was not as evident with the lower doses. All doses produced areas of hyperplastic epithelium alternating with areas of pleomorphic-atrophic epithelium. Although the differences in predominance of different types of epithelium was not clearly dose-dependent, the labeling index (LI) showed dose dependence between 2 and 4 weeks after initiation of exposure. The maximum mean LI was three to four times higher than normal, although in some focal hyperplastic-metaplastic lesions the LI was increased up to 20 times. These studies show that formaldehyde, although toxic at higher doses, is able to elicit at lower doses a proliferative response of the human respiratory epithelium that is not preceded by a massive toxic effect. This response is similar, although less intense than that of the rat respiratory epithelium in which formaldehyde proved to be a carcinogen. PMID- 2913831 TI - Effects of the antismoking campaign: an update. AB - In the absence of the antismoking campaign, adult per capita cigarette consumption in 1987 would have been an estimated 79-89 per cent higher than the level actually experienced. The smoking prevalence of all birth cohorts of men and women born during this century is well below that which would have been expected in the absence of the campaign. As a consequence, in 1985 an estimated 56 million Americans were smokers; without the campaign, an estimated 91 million would have been smokers. As a result of campaign-induced decisions not to smoke, between 1964 and 1985 an estimated 789,200 Americans avoided or postponed smoking related deaths and gained an average of 21 additional years of life expectancy each; collectively this represents more than 16 million person-years of additional life. The greatest health benefit lies in the future, however, as younger individuals reach the ages at which smoking claims its greatest toll, and as middle-aged former smokers realize relative reductions in smoking mortality risks as a result of long-term abstinence from smoking. For example, campaign induced decisions not to smoke made prior to 1986 will result in the postponement or avoidance of an estimated 2.1 million smoking-related deaths between 1986 and the year 2000. PMID- 2913832 TI - International comparisons of trends in cigarette smoking prevalence. AB - Data on smoking prevalence since 1974 are presented for the United States, Canada, Great Britain, Australia, Norway and Sweden. During this period, sex specific prevalence has decreased in all the countries studied, with the exception of Norway, where women showed an increase. There was also a considerable decline in uptake of smoking by the young over this period, suggesting that the observed decline in prevalence is likely to continue. In the United States, the rate of decline in adult smoking prevalence has been linear. This linear pattern is probably similar in prevalence in most other countries studied, with the notable exception of Australia, which demonstrated no change for the majority of the period. Among the six countries studied, the United States had neither the lowest smoking prevalence nor the fastest rate of decline over the period. Differential patterns of change infer that the successful public health interventions in some countries are not being applied in others. While the lack of change in Australia prior to 1983 is surprising, this was followed by a sizable drop in smoking prevalence for both higher and lower educational groups in conjunction with the introduction of mass media-led antismoking campaigns. Most of the other countries report an ever increasing gap in prevalence between higher and lower educational groups. These findings suggest that all countries might benefit from a greater exchange of antismoking ideas and public health action. PMID- 2913833 TI - The influence of smoking on vitamin C status in adults. AB - To further define the relation between smoking and vitamin C status, the dietary and serum vitamin C levels of 11,592 respondents in the second National Health and Nutrition Examination Survey (NHANES II) were analyzed. Smokers of 20 cigarettes daily had the lowest vitamin C dietary intake (79 mg, 95% CI:73, 84) and serum levels (0.82 mg/dl, 95% CI: 0.77, 0.86; 46.6 mumol/L, 95% CI: 43.7, 48.8), while smokers of 1-19 cigarettes daily had decreased vitamin C intake (97 mg; 95% CI: 90, 104 mg) and serum levels (0.97 mg/dl, 95% CI: 0.92, 1.03; 55.1 mumol/L, 95% CI: 52.2, 58.5) compared to respondents who had never smoked (109 mg, 95% CI: 105, 113 and 1.15 mg/dl, 95% CI: 1.11, 1.18; 65.3 mumol/L, 95% CI: 63.0, 67.0, respectively). This inverse association between both intake and serum levels of vitamin C and smoking was independent of age, sex, body weight, race, and alcoholic beverage consumption. Following further adjustment for dietary vitamin C intake, the negative correlation between cigarette smoking and serum vitamin C levels persisted. The risk of severe hypovitaminosis C (serum levels less than or equal to 0.2 mg/dl; 11.4 mumol/L) was increased in smokers, particularly when not accompanied by vitamin supplementation (odds ratio 3.0, 95% CI: 2.5, 3.6). These data suggest that even though smoking adversely affects preferences for vitamin C rich foods, the inverse association between smoking and serum vitamin C levels occurs independently of dietary intake. PMID- 2913834 TI - Deaths from all causes in non-smokers who lived with smokers. AB - Mortality associated with passive smoking was evaluated in a 12-year study of 27,891 White adult smokers and 19,035 never smokers identified in 1963. Death rates were calculated using an estimate of the person-years at risk. Adjusted for age, marital status, education, and quality of housing, the estimated relative risks of death from all causes were 1.17 (approximate 95% confidence interval 1.01, 1.36) for men and 1.15 (1.06, 1.24) for women with passive exposure. These relative risks were similar to those for ex-smokers and for pipe or cigar smokers. Risks increased slightly with level of exposure. The relative risk from passive smoking was greatest for men under age 50 (RR = 2.09, 1.31-3.34). Risks from passive smoking were slightly elevated for several causes among men and women, and may be broader than those previously reported. On the other hand, these small nonspecific increases in death rates may reflect other characteristics of passive smokers that increase mortality. PMID- 2913835 TI - Nicotine intake in young smokers: longitudinal study of saliva cotinine concentrations. AB - Smoking habits and smoke intake were studied over three consecutive years in 197 girls, initially aged 11 to 14 years. Saliva cotinine concentrations in girls who were smokers throughout the three years increased over each year of the study, the greatest increase occurring during movement from occasional to daily smoking. Cigarette consumption also increased over the two years. For a group of continuing daily smokers (n = 23), inhalation of smoke per cigarette as indexed by the ratio of cotinine concentration to average daily cigarette consumption did not change over time. Cotinine concentrations in 16 girls who were smoking on a daily basis within a year of starting to smoke suggested the early development of inhalation. Our findings suggest that young smokers learn to inhale cigarette smoke very early in their smoking careers, that further increases in smoke intake mainly reflect increased cigarette consumption, and that the pharmacological effects of nicotine are already important in reinforcing their smoking. PMID- 2913836 TI - A survey of smoking and quitting patterns among black Americans. AB - A sample of adult Black policyholders of the nation's largest Black-owned life insurance company was surveyed in 1986 to add to limited data on smoking and quitting patterns among Black Americans, and to provide direction for cessation initiatives targeted to Black smokers. Forty per cent of 2,958 age-eligible policyholders for whom current addresses were available returned a completed questionnaire. Population estimates for smoking status agree closely with national estimates for Blacks age 21-60 years: 50 per cent never-smokers; 36 per cent current smokers; 14 per cent ex-smokers. Current and ex-smokers reported a modal low-rate/high nicotine menthol smoking pattern. Current smokers reported a mean of 3.8 serious quit attempts, a strong desire and intention to quit smoking, and limited past use of effective quit smoking treatments and self-help resources. Correlates of motivation to quit smoking were similar to those found among smokers in the general population, including smoking-related illnesses and medical advice to quit smoking, previous quit attempts, beliefs in smoking related health harms/quitting benefits, and expected social support for quitting. Methodological limitations and implications for the design of needed Black focused quit smoking initiatives are discussed. PMID- 2913837 TI - A randomized trial of a serialized self-help smoking cessation program for pregnant women in an HMO. AB - We report the results of a population-based randomized clinical trial that tested the effectiveness of a prenatal self-help smoking cessation program. The intervention consisted predominantly of printed materials received through the mail. The population (n = 242) consisted of a socioeconomically and ethnically diverse group of pregnant women enrolled in a large health maintenance organization (HMO) who reported they were smoking at the time of their first prenatal visit. Biochemical confirmation of continuous abstinence achieved prior to the 20th completed week of pregnancy and lasting through delivery revealed 22.2 per cent of the women in the eight-week serialized program quit versus 8.6 per cent of controls with usual care. The adjusted odds ratio was 2.80 (95 per cent CI = 1.17, 6.69). We conclude that a low-cost prenatal self-help intervention can significantly affect the public health problem of smoking during pregnancy and its associated risks for maternal and child health. PMID- 2913838 TI - Compensation as a risk factor for lung cancer in smokers who switch from nonfilter to filter cigarettes. AB - The likelihood of increasing the number of cigarettes per day (cpd), a common method of compensation, in smokers switching from nonfilter to filter cigarettes, was examined in newly diagnosed and histologically confirmed lung cancer cases including all cell types; 1,242 lung cancer cases and 2,300 sex and age matched hospital controls were interviewed in 20 hospitals from nine United States cities between 1969 and 1984. The mean increase in cpd for lung cancer cases was about twice that of controls. Using switchers who did not increase cpd as the referent group, there was a linear dose-response relationship between the odds of lung cancer and increasing level of compensation. The odds ratio increased from 1.19 to 2.37 in males and from 1.66 to 3.83 in females corresponding to increases of 1 10 to 21+ cpd after switching. Findings from this study suggest that increasing cpd after switching to filter cigarettes is an important risk factor for lung cancer that needs to be emphasized in epidemiologic studies. Proponents of the idea that switching cigarettes is of some benefit, should also advocate that individuals who continue smoking should avoid compensation after switching. PMID- 2913839 TI - A comparative evaluation of a restrictive smoking policy in a general hospital. AB - The impact of a restrictive smoking policy on the behavior and attitudes of smokers and non-smokers was assessed by surveying random cross-sectional samples of hospital employees before, six months after and 12 months after the policy was implemented, and comparing responses with those of employees of a hospital with no restrictive policy. Effectiveness of policy implementation was also evaluated. Results indicated that the policy was well-publicized and was approved by virtually all the non-smokers and the majority of the smokers. Following implementation, employees in the smoking policy hospital were less likely to report being bothered by smoke at their work stations than were employees of the comparison hospital. Six months and one year after the policy change, smokers reported lower smoking rates while at work, although quit smoking rates and home smoking rates were similar in both hospitals. PMID- 2913841 TI - Evidence for limits on the acceptability of lowest-tar cigarettes. AB - The sales of the lowest yield cigarettes (1-3 mg tar) seem to have been particularly resistant to the effects of promotion and advertising, while the sales of other low-yield cigarettes (4-9 mg tar) seem to have been increased by promotional efforts. This finding is consistent with the existence of a boundary of tar and nicotine acceptability below which consumers in general are not prepared to go. Use of lower tar cigarettes may be helpful for those who cannot stop smoking, but, since 1979, the percentage of cigarettes under 16 mg tar has changed little. PMID- 2913840 TI - Cigarette smoking among San Francisco Hispanics: the role of acculturation and gender. AB - We conducted a phone survey of 1,669 San Francisco Hispanics ages 15 to 64 years. The age-adjusted overall smoking prevalence was 25.4 per cent (95% CI = 23.3, 27.5) with more men (32.4 per cent) smoking than women (16.8 per cent). Age adjusted smoking rates were higher among the less acculturated males (37.5 vs 26.7 per cent) and among the more acculturated females (22.6 vs 13.6 per cent). The more acculturated, however, smoked a greater number of cigarettes per day independent of gender. Community-based smoking cessation interventions, adapted to local conditions, may have a greater potential for success among Hispanics. PMID- 2913842 TI - Accuracy of recalled smoking data. AB - Validity of recalled cigarette data was assessed among 87 middle-aged adults by comparing recall to longitudinal records. Agreement on smoking status and amount smoked 20 years ago occurred for 87 per cent and 71 per cent of subjects, respectively. Corresponding proportions for 32-year recall were 84 per cent and 55 per cent. Gender did not influence recall accuracy. Ex-smokers tended to make the most errors. Accuracy of recalled smoking information 20 years ago was comparable to that of alcohol status and consumption frequency category. PMID- 2913843 TI - Validity of telephone surveys in assessing cigarette smoking in young adults. AB - Self-reports of cigarette smoking in a sample of young adults, aged 17 to 21 (n = 359) obtained by telephone were validated by home interview and saliva cotinine measurement. While most subjects were in agreement for their reported behaviors, the telephone methodology underestimated cigarette smoking rates by 3 to 4 per cent. Reported quitting by telephone was an unstable category with 35 per cent of quitters reporting smoking on home interview. Reliance on telephone methods alone may underestimate smoking behavior. Validation of surveys, preferably by biochemical methods, is recommended. PMID- 2913844 TI - Patient literacy and the readability of smoking education literature. AB - This study was designed to determine if primary care clinic patients read at a level congruent to the reading grade level of available smoking literature. Reading estimates of smoking education literature (N = 49) ranged from grade 3 to college level (median = 9.5). Reading skills of 258 smoking patients were estimated by reported years of schooling (median = 10), and by scores on the Wide Range Achievement Test (median = 6). A serious disparity existed between the reading estimates of smoking education literature and the literacy skills of patients in our sample. PMID- 2913845 TI - Age of initiation and switching patterns between smokeless tobacco and cigarettes among college students in the United States. AB - A stratified, random, multi-stage, cluster sample of physical activity classes among 72 colleges and universities throughout the United States yielded 5,894 usable responses (males = 2,888); (females = 3,006). Twenty-three per cent of the students who began smoking before the age of 10 were current smokers, while 61 per cent of those who began using smokeless tobacco before the age of 10 were current smokeless tobacco users. College students were more likely to switch from smokeless tobacco to cigarettes than from smoking cigarettes to smokeless tobacco. PMID- 2913846 TI - Children's health promotion. PMID- 2913847 TI - Prophylactic transdermal scopolamine patches reduce nausea in postoperative patients receiving epidural morphine. AB - To evaluate the efficacy of prophylactic transdermal scopolamine in reducing nausea associated with postoperative epidural analgesia, we studied 32 healthy adult women undergoing major gynecologic surgery. The patients were randomized in a double blind fashion to receive either a cutaneous scopolamine patch or a visually identical cutaneous placebo patch. Postoperative analgesia was provided solely with epidural morphine. Nausea was treated with metoclopramide and droperidol. At 24 hours postoperatively, the mean nausea score was significantly lower with scopolamine than with placebo (1 +/- 2 vs 51 +/- 42, respectively, P less than 0.05). The number of patients reporting "zero nausea" was significantly greater with scopolamine patches than with placebo patches (13 vs 1, P less than 0.01). The mean number of times antiemetic drugs were administered per patient was lower with scopolamine than with placebo patches (0.2 +/- 0.4 vs 2.8 +/- 2.6, P less than 0.05). It is concluded that prophylactic transdermal scopolamine patches reduce nausea in postoperative patients receiving epidural morphine. PMID- 2913848 TI - Metabolism of I-653 and isoflurane in swine. AB - Fluoride ion concentrations were measured in plasma samples taken from chronically instrumented domestic swine before, immediately after, and 4 hours after exposure to either I-653 or isoflurane. Each anesthetic was administered at concentrations between 0.7 and 1.6 MAC and the total dose of anesthetic given was approximately 5.5 MAC hours for each agent. Plasma fluoride ion concentrations immediately after and 4 hours after exposure to isoflurane were approximately three times greater than values obtained in awake swine before anesthesia. In contrast, swine given I-653 had no detectable elevation in plasma fluoride concentration immediately after anesthesia, but a 17% (P less than 0.05) increase in plasma fluoride ion concentration 4 hours after anesthesia. These results imply that I-653 is metabolized less than is isoflurane in swine. PMID- 2913849 TI - The lumbar epidural space in patients examined with epiduroscopy. AB - Percutaneous epiduroscopy was performed in 10 patients with the aim of comparing the lumbar epidural space of the patients with the findings made earlier in autopsy subjects. The patients were scheduled for partial laminectomy for a herniated lumbar disc. A complete examination was possible in eight subjects. The extent of view was very limited. The epidural space opened up only temporarily as air was injected. The dura mater lay very close to the dorsal aspect of the epidural space and was attached to the flaval ligaments by a dorsomedian connective tissue band. The band was identified in all eight subjects and was found to cause a dorsal fold in the dura mater. An epidural catheter was introduced 2-5 cm into the space by midline puncture in four patients and by the paramedian approach in the other four. The catheter was visualized in two patients only when the paramedian approach was used. None of the midline catheters could be seen in the space. In 2 of the 10 subjects a moderate bleeding impaired the view and made complete examination impossible. Smaller bleeding occurred in three other subjects. The partial laminectomy performed one to two interspaces caudad to the level of endoscopy did not reveal any evidence of epidural bleeding in any subject. The postoperative course of all patients was uneventful. PMID- 2913850 TI - Anesthesia unmasking benign Wolff-Parkinson-White syndrome. PMID- 2913851 TI - General anesthesia and fibrodysplasia ossificans progressiva. PMID- 2913852 TI - Is magnesium sulfate an anesthetic? PMID- 2913853 TI - Epidural fentanyl as a test dose. PMID- 2913854 TI - Caudal anesthesia in pediatric surgery: success rate and adverse effects in 750 consecutive patients. AB - The success rate and occurrence of adverse effects are reported in a retrospective study of 750 caudal analgesias in children. In 94% of the patients, the blocks were performed under light general anesthesia. Standard IM or short beveled needles were used in all. Four anesthetic solutions of lidocaine and/or bupivacaine with 1:200,000 epinephrine were injected in volumes ranging from 0.5 to 1.25 ml/kg. The overall success rate of caudal blocks was 96%, but several attempts were necessary in 25% of patients. Most failures occurred in children more than 7 years old. The use of short-beveled needles considerably decreased the number of traumatic punctures. The upper limit of analgesia varied widely and appropriate distribution of anesthesia was reliably obtained only after the injection of 0.75 to 1.0 ml/kg of local anesthetic solution. Conscious children tolerated surgery poorly (from a psychological point of view) although they were free of pain. Conversely, breathing difficulties occurred in 12% of lightly anesthetized patients. Hemodynamic disturbances were infrequent, as were adverse effects except for postoperative vomiting (17%). Motor block, present in 54% of patients, was poorly tolerated postoperatively by 10% of patients. Long-lasting postoperative pain relief was usually obtained. There were no major complications or neurological sequelae and good patient and parental acceptance of caudal anesthesia. Caudal anesthesia is a reliable and safe technique in young children. PMID- 2913855 TI - Clinical pharmacokinetics of carbonated local anesthetics. III: Interscalene brachial block model. AB - To compare serum levels of lidocaine resulting from 1.1% lidocaine carbonate and 1.0% lidocaine hydrochloride, the two salts were administered to ten healthy adult patients undergoing upper extremity surgery under interscalene brachial plexus block. Epinephrine (1:200,000) was added to both the solutions just prior to injection, and, following performance of the blocks, venous blood samples were drawn at 3, 5, 10, 15, 20, 30, 60 and 120 minutes. The concentration of lidocaine tended to rise more rapidly and to achieve higher levels in the first 10 minutes following injection of the carbonated lidocaine. However, no significant differences were found in the parameters of Cmax, Tmax or AUC for the two salts, and the serum levels in both groups at all times were well below the levels known to produce systemic toxicity. Therefore, while previous studies appear to indicate that the carbonate salt enhances diffusion, penetration, and uptake of neural tissues as compared with the hydrochloride salt, the present study indicates that vascular uptake is not similarly affected. PMID- 2913856 TI - Anesthetics, coronary artery disease, and outcome: unresolved controversies. PMID- 2913858 TI - Fentanyl-induced ventilatory depression: effects of age. AB - To determine whether infants are more sensitive than older patients to the ventilatory-depressant effects of fentanyl, patients were anesthetized with fentanyl and nitrous oxide (N2O) and ventilatory depression was assessed following elimination of N2O and in the immediate postoperative period. Three groups of patients were studied: infants (1-12 mo old, n = 14), children (1-5 yr old, n = 14), and adults (23-38 yr old, n = 13). Skin-surface PCO2 was measured to determine the peak PCO2 occurring at the end of anesthesia when end-tidal N2O concentration was less than 6%. Naloxone was administered if PCO2 exceeded 70 mmHg. During recovery from anesthesia, ventilatory pattern was recorded using impedance pneumography to determine the longest breath-to-breath interval and the number of episodes of central apnea (defined as breath-to-breath intervals greater than or equal to 10 s in infants and children and greater than or equal to 20 s in adults). Elevation of PCO2 correlated with increasing plasma fentanyl concentrations but did not differ between groups. Four patients (two infants, one child, and one adult) required naloxone. The only subject who had a low plasma fentanyl concentration but required naloxone was a 6-wk-old infant; this was the only subject younger than 3 mo. For each range of fentanyl concentrations, the incidence of apnea increased with age, as did the number of episodes of apnea per subject. Fentanyl-induced ventilatory depression, as assessed by elevation of resting PCO2 during emergence from anesthesia and disruption of ventilatory pattern during recovery from anesthesia, is not greater in infants older than 3 mo than in children and adults.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2913857 TI - Effect of pulmonary artery catheterization on outcome in patients undergoing coronary artery surgery. AB - Previous studies have suggested that low-risk cardiac surgical patients may be safely managed without pulmonary artery catheterization (PAC). However, no prospective studies have determined whether PAC improves outcome in higher risk patients compared with that following central venous pressure (CVP) monitoring alone. The authors prospectively examined the incidence of and factors related to perioperative morbidity and mortality in 1094 consecutive patients undergoing coronary artery surgery managed with elective PAC (n = 537) or with CVP (n = 557). Perioperative risk factors and demographics that predict morbidity and mortality after cardiac surgery were used to quantify risk classification. Outcome was judged by length of ICU stay, occurrence of postoperative myocardial infarction, in-hospital death, major hemodynamic aberrations, and significant noncardiac systemic complications. No significant differences in any outcome variables were noted in any group of patients with similar quantitative risk classification managed with or without PAC, including those in the highest risk class. In addition, there were no significant differences in outcome among the 39 patients who would have been managed with CVP monitoring only, but who subsequently developed a clinical need for PAC based on the occurrence of serious hemodynamic events compared to patients who had PAC performed electively. This study suggests that PAC does not play a major role in influencing outcome after cardiac surgery, that even high-risk cardiac surgical patients may be safely managed without routine PAC, and that delaying PAC until a clinical need develops does not significantly alter outcome, but may have an important impact on cost savings. PMID- 2913859 TI - Intrathecal fentanyl depresses nociceptive flexion reflexes in patients with chronic pain. AB - To investigate the selective role of intraspinal opioids on the perception and modulation of pain, seven subjects with chronic hip or back pain and one subject with C-6 quadriplegia received 25 micrograms of intrathecal fentanyl. The effect of lumbar intrathecal fentanyl on reported pain, nociceptive flexor withdrawal reflexes, a monosynaptic motor arc (H-reflex), and supraspinal effects such as miosis, nausea, respiratory depression was evaluated. In five of eight subjects the flexor withdrawal reflex was completely abolished within 15 min. In the others the reflex was significantly depressed from control values. Decreases in reported pain paralleled the decrease in the flexor reflex, H-reflexes remained unchanged, and no supraspinal side effects were observed. It is likely that these selective changes observed were from the isolated effect of fentanyl modulating nociception at the spinal cord level. PMID- 2913860 TI - Cerebral blood flow and cerebral oxygen consumption during nitroprusside-induced hypotension to less than 50 mmHg. AB - The authors determined the effect of profound induced hypotension (i.e., mean arterial blood pressure less than 50 mmHg) during craniotomy for cerebral aneurysm on cerebral blood flow and cerebral metabolic rate for oxygen before, during, and after (20 min and 40 min after) the hypotensive period. The study was performed on nine adults (mean age, 29.2 yr) who were awake and conscious without peripheral neurologic deficits at the time of surgery. The study was conducted with the dura open with the use of a radial artery cannula, a 7-Fr thermodilution flow-directed pulmonary artery catheter, and an internal jugular vein catheter. The 133xenon intraarterial injection technique was used to determine regional cerebral blood flow (rCBF) in the nonoperated hemisphere. rCBF remained unchanged (from 22.8 +/- 4.1 ml.100 g-1.min-1 to 23.8 +/- 4.6 ml.100 g-1.min-1) during the hypotensive period (MAP from 87.8 +/- 10.4 mmHg to 40.0 +/- 4.4 mmHg; P less than 0.001) despite an increase in cardiac index since cerebral perfusion pressure and cerebrovascular resistance decreased to a similar degree. No gross cerebral metabolic disturbances were observed. A period of decreased cerebrovascular resistance and increased rCBF followed induced hypotension. rCBF increased from 23.8 +/- 4.6 ml.100 g-1.min-1 to 30.0 +/- 5.8 ml.100 g-1.min-1 (P less than 0.001) 20 min after sodium nitroprusside (SNP) was stopped without rebound hypertension. These modifications disappeared 20 min later. Reduction of mean arterial blood pressure to 40 mmHg by SNP was apparently safe for the brain, although the possibility of low perfused regions and local brain and cerebrospinal fluid lactoacidosis, particularly in the retracted hemisphere, cannot be excluded. PMID- 2913861 TI - Protamine inhibits plasma carboxypeptidase N, the inactivator of anaphylatoxins and kinins. AB - Protamine given to neutralize heparin after extracorporeal circulation can trigger a catastrophic reaction in some patients. While searching for a biochemical basis for this reaction, protamine was tested as an inhibitor of human plasma carboxypeptidase N (CPN) or kininase I, the inactivator of anaphylatoxins and kinins. Human plasma and CPN purified from human plasma, (Mr = 280 K) or its isolated active subunit (Mr = 48 K) were the sources of enzyme. The hydrolysis of furylacryloyl (FA)-Ala-Lys was measured in a UV spectrophotometer and that of bradykinin and the synthetic C-terminal octapeptide of anaphylatoxin C3a (C3a8) by high performance liquid chromatography. Protamine inhibited the hydrolysis of FA-Ala-Lys by CPN, (IC50 = 3.2 X 10(-7) M); added human serum albumin (30 mg/ml) increased the IC50 to 7 X 10(-6) M. When plasma was the source of CPN, the IC50 was 2 X 10(-6) M. Protamine more effectively inhibited the hydrolysis of bradykinin and C3a8. The IC50 for protamine was 5 X 10(-8) M with CPN and bradykinin, 7 X 10(-8) M with CPN and C3a8 and with the 48 K subunit and bradykinin it was 7 X 10(-8) M of protamine. Heparin competes with CPN for protamine, because in high concentration (18 U/ml) it reverses the inhibition by protamine. Protamine did not inhibit angiotensin I converting enzyme (kininase II) or the endopeptidase 24.11 (enkephalinase). Kinetic studies showed the mechanism of protamine inhibition to be partially competitive; about 10-20% of the hydrolysis of bradykinin by CPN was not inhibited by protamine. Thus, by blocking the inactivation of mediators released in shock, protamine inhibition of CPN may be partially responsible for the catastrophic reaction observed to occur in some patients. PMID- 2913862 TI - Phenylephrine increases regional cerebral blood flow following hemorrhage during isoflurane-oxygen anesthesia. AB - Using the radioactive microsphere technique regional cerebral blood flow (rCBF) and total CBF (tCBF) were examined in rats at three time periods: baseline (CBF1) during 1.5 MAC inspired isoflurane-oxygen anesthesia, CBF2; during 1.5 MAC inspired isoflurane anesthesia combined with hypotension induced by hemorrhage and CBF3; during isoflurane and hemorrhage plus phenylephrine infused to restore mean arterial pressure (MAP) to baseline. For CBF1 MAP was 89 +/- 3 mmHg (mean +/ SEM, n = 9) with PaCO2 44 +/- 1 mmHg. For CBF2 following graded hemorrhage MAP was 48 +/- 2 mmHg and PaCO2 43 +/- 1 mmHg. For CBF3 MAP was 93 +/- 2 and PaCO2 45 +/- 1 mmHg, following infusion of phenylephrine (PE) at 13.9 +/- 4.0 micrograms.kg-1.min-1. Total CBF1 was 1.84 +/- 0.18 ml.g-1.min-1, tCBF2 1.32 +/- 0.09 ml.g-1.min-1 (P less than 0.05 vs. tCBF1) and tCBF3 2.60 +/- 0.18 (P less than 0.05 vs. tCBF1 and 2). For tCBF3 hemoglobin concentration had decreased 23% from 14.2 +/- 0.2 g.100 ml-1 to 11.0 +/- 0.5 g.100 ml-1 (P less than 0.05). Regional CBF decreased significantly in seven of 12 regions examined from CBF1 to CBF2 and was significantly higher in all regions for CBF3. For CBF1-3 infratentorial blood flows (cerebellar and brain stem) were significantly higher than flows to the supratentorial structures (cerebral cortical and basal ganglia). During isoflurane anesthesia, phenylephrine infused to support MAP following hemorrhagic hypotension effectively maintains rCBF and tCBF. There is no indication that phenylephrine infused to increase MAP following hemorrhage results in cerebral vasoconstriction in rats anesthetized with isoflurane. PMID- 2913863 TI - The magnitude and duration of direct myocardial depression following intracoronary local anesthetics: a comparison of lidocaine and bupivacaine. AB - Direct myocardial depression plays a role in the cardiovascular toxicity of local anesthetic agents, but this role is obscured by concomitant cardiac, systemic, and CNS events: seizures, hypoxia, acidosis, sympathetic activation, bradycardia, and A-V heart block. Direct injection of small bolus doses of lidocaine and bupivacaine into a branch of the left coronary artery was used to minimize these systemic effects. Regional contraction in the zone supplied by the coronary artery was measured with a sonomicrometer. Both agents caused a dose-dependent reduction in the extent of systolic contraction, and a 4.9:1 (lidocaine:bupivacaine) dose ratio produced a 50% depression of contraction. The duration of depression, taken as the time for 95% recovery of systolic contraction, was about 25% (P less than 0.05) longer with bupivacaine for an equal degree of depression. Coronary blood flow was reduced modestly by both agents. These results suggest that differences in the magnitude or duration of direct myocardial depression cannot explain the clinical perception that the cardiovascular toxicity of bupivacaine is greater than that of lidocaine. PMID- 2913864 TI - The effect of intravenously administered 2-chloroprocaine upon uterine artery blood flow velocity in gravid guinea pigs. AB - The purpose of the present study was to assess the effect of intravenously administered 2-chloroprocaine upon uterine artery blood flow velocity (UBFV) in gravid guinea pigs. Ten experiments were performed in ten chronically instrumented animals between 0.7 and 0.9 of timed gestation. Each animal received four solutions of 2-chloroprocaine in random order: 1) 0.67 mg/kg; 2) 1.34 mg/kg; 3) 2.0 mg/kg; and 4) 1.34 mg/kg, with epinephrine 0.2 microgram/kg. Six animals received a fifth solution, 0.2 ml of saline control. 2-Chloroprocaine 1.34 mg/kg significantly increased maternal mean arterial pressure (MMAP) at 30 s after injection, and 2-chloroprocaine 2.0 mg/kg significantly increased MMAP through 2 min. 2-Chloroprocaine 1.34 mg/kg, with epinephrine 0.2 microgram/kg, also significantly increased MMAP through 2 min. No other solution significantly altered MMAP. 2-Chloroprocaine 2.0 mg/kg significantly decreased UBFV at 30 s after injection. 2-Chloroprocaine 1.34 mg/kg, with epinephrine 0.2 microgram/kg, significantly decreased UBFV through 2 min. No other solution significantly altered UBFV. The authors conclude that iv administration of 2-chloroprocaine with epinephrine significantly decreased UBFV in pregnant guinea pigs. In contrast, only the largest dose (i.e., 2.0 mg/kg) of 2-chloroprocaine alone transiently decreased UBFV. These data suggest that, in doses up to 1.34 mg/kg, 2 chloroprocaine alone may not decrease uterine blood flow when used as a marker for intravenous injection in obstetric patients. PMID- 2913865 TI - The opiate antagonist naloxone counteracts the inhibition of sympathetic nerve activity caused by halothane anesthesia in rats. AB - The study was undertaken to examine if endogenous opioid systems mediate the response of the sympathetic nervous system to halothane anesthesia. Steady state values of renal sympathetic nerve activity (rSNA), mean arterial pressure (MAP), and heart rate (HR) were continuously recorded in the conscious state and at three depths of halothane anesthesia (0.6%, 1.2%, and 2.4%) in rats. Halothane caused an inhibition of rSNA and hypotension and a decrease in HR at the three halothane concentrations. Repeated bolus doses of the opiate antagonist ( )naloxone given iv during 1.2% halothane anesthesia did not significantly increase any of the variables. However, pretreatment with (-)naloxone (2 or 15 mg.kg-1) induced an increase in rSNA at 0.6% halothane, and subsequently the rSNA inhibition was less pronounced at the two higher halothane concentrations compared with control. HR showed a similar pattern, whereas the hypotension was essentially unaffected. Pretreatment with the pharmacologically inactive compound (+)naloxone had no effect on the halothane-induced depression of rSNA. The ED50 halothane concentration concerning nociceptive aversive behavior was not significantly changed with (-)naloxone pretreatment (2 mg.kg-1). In order to determine if sympathoinhibitory bulbospinal serotonin pathways are activated during halothane anesthesia, rSNA, MAP, and HR were recorded in rats pretreated with the serotonin synthesis inhibitor parachlorophenylalanine (PCPA). However, PCPA pretreatment did not affect the rSNA response to halothane compared with control. These findings indicate that the halothane-induced inhibition of rSNA might partially result from a stereospecific activation of opioid receptors, whereas halothane analgesia does not seem to be mediated by opioid mechanisms. PMID- 2913866 TI - Effect of midazolam and diazepam premedication on central nervous system and cardiovascular toxicity of bupivacaine in pigs. AB - To determine the effect of benzodiazepine premedication on central nervous system and cardiovascular effects of bupivacaine, the authors administered toxic doses of bupivacaine to awake spontaneously breathing pigs after intravenous premedication with midazolam (0.06 mg/kg), diazepam (0.15 mg/kg), or saline. Five minutes after administration of one of these solutions, they began an infusion of bupivacaine at 2 mg.kg-1.min-1. The bupivacaine infusion was continued until cardiovascular collapse. They then attempted to resuscitate the animals via open chest cardiac massage and a standard resuscitation protocol. Premedication with midazolam or diazepam significantly delayed the onset of ventricular dysrhythmias (P less than 0.05), decreased the incidence of seizures (P less than 0.05), and prevented the increase in blood pressure and heart rate following bupivacaine infusion (P less than 0.05). Benzodiazepine premedication did not affect the dose of bupivacaine or the blood concentration required to produce cardiovascular collapse. The ability to resuscitate animals premedicated with midazolam did not differ from control; however, significantly fewer animals premedicated with diazepam were resuscitated (P less than 0.05). A clinically relevant observation was that almost all animals premedicated with a benzodiazepine progressed directly to cardiovascular collapse without first manifesting seizures. PMID- 2913867 TI - The measurement of expiratory oxygen as disconnection alarm. AB - The efficacy of an oxygen-monitoring alarm in the expiratory limb of an anesthetic circuit was evaluated as a method of detecting disconnections of the patient from the anesthetic machine. Oxygen concentrations were determined in the expiratory limb of a semiclosed anesthetic circuit with a ventilator and a 2-1 reservoir bag serving as a simple lung model. Adjustments of ventilation during the different measurements were a PEEP of 5 cmH2O, respiratory rates of 10/min and 5/min, and tidal volumes of 1,000 and 500 ml, respectively. The alarm time measured with a stopwatch was the time that elapsed between disconnection and the acoustical alarm. The circuit was always disconnected at the y-piece when the reservoir bag had been fully expanded after an inspiration. With various fresh flow rates and oxygen concentrations ranging from 33% to 52%, disconnection always was evident within 30 s. Measurement of the oxygen concentration with an alarm time of 30 s after disconnection may be an effective backing system for detecting a disconnection. PMID- 2913868 TI - Insufficient anesthetic potency of nitrous oxide in the rat. AB - Nitrous oxide (N2O) is frequently used for maintenance of anesthesia in research animals because of its minimal effect upon circulatory variables and the ability to rapidly alter its anesthetic concentration. However, N2O's low anesthetic potency may result in inadequate levels of anesthesia under experimental conditions; thus, the ability of N2O to provide adequate anesthesia during tracheal stimulation in rats, following withdrawal of halothane was evaluated. Twenty rats of similar ages and weights were anesthetized with halothane (1.44% inspired) and their tracheas orally intubated. Ten minutes prior to the conclusion of a 90-min halothane stabilization period, either 70% N2O (n = 10) or 70% nitrogen (n = 10) was added to the inspired anesthetic gas mixture. The halothane was discontinued at the conclusion of the 90-min period and each rat was observed for spontaneous motor behavior while end-expiratory anesthetic gases were intermittently measured with mass spectrometry. The halothane concentrations present at the times of four specific, consistently occurring behaviors were measured, and comparisons were made between the N2O and nitrogen groups by a mean t test. There were no significant differences (P less than 0.05) in the halothane concentration between the N2O and nitrogen groups in three of the four behaviors compared: 1) change in respiratory pattern, 2) purposeful movement of the torso, and 3) purposeful self-extubation. In the fourth behavior (purposeful movement of an extremity) the halothane concentration was higher in the N2O group than in the nitrogen group. A mean halothane concentration of 0.49% was required to prevent the purposeful behaviors in the presence of N2O.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2913869 TI - Clinical evaluation of a Raman scattering multiple gas analyzer for the operating room. AB - A Raman spectrometer multiple gas analyzer was used to monitor inspired and expired concentrations of oxygen (O2), nitrogen (N2), carbon dioxide (CO2), nitrous oxide (N2O), halothane, and isoflurane in 10 patients. The Raman spectrometer and a dedicated mass spectrometer were connected to each patient to provide a comparison of the two instruments. Results show that readings from the Raman spectrometer are within 0.62 vol% of known gas standards for O2, N2, N2O; within 0.03 vol% for CO2; and within 0.04 vol% for halothane, enflurane and isoflurane. Clinical results show that Raman spectrometer readings are within 1.36 vol% of the mass spectrometer readings for O2, N2, N2O; within 0.01 vol% for CO2; and within 0.22 vol% for halothane and isoflurane. The clinical and laboratory results indicate the Raman spectrometer monitors airway gases and vapors as accurately as a dedicated mass spectrometer. PMID- 2913870 TI - The processed electroencephalogram may not detect neurologic ischemia during carotid endarterectomy. PMID- 2913871 TI - Posterior arytenoid dislocation following uneventful endotracheal intubation and anesthesia. PMID- 2913872 TI - Sevoflurane anesthesia with adenosine triphosphate for resection of pheochromocytoma. PMID- 2913873 TI - Reflex sympathetic dystrophy syndrome in pregnancy. PMID- 2913874 TI - Prevention of hypokalemia during axillary nerve block. PMID- 2913875 TI - The needle tilt test: an aid to epidural needle insertion. PMID- 2913876 TI - Blood flow limits and signal detection comparing five different models of pulse oximeters. PMID- 2913877 TI - A greengrocer's model of the epidural space. PMID- 2913878 TI - Skin circulation and the thermoregulatory threshold. PMID- 2913879 TI - More on thermoregulatory thresholds with halothane. PMID- 2913880 TI - Inhibition of carnitine palmitoyltransferase by malonyl-CoA in human muscle is influenced by anesthesia. PMID- 2913881 TI - Caution when using a Tubex cartridge without the injector. PMID- 2913882 TI - A new adapter for fiberoptic endotracheal intubation for anesthetized patients. PMID- 2913883 TI - The "destructive index" in nonemphysematous and emphysematous lungs. Morphologic observations and correlation with function. AB - We examined the relationship of the newly described "Destructive Index" (DI) to emphysema using nine nonemphysematous and 13 emphysematous lungs obtained at autopsy. The amount of emphysema was assessed by the panel method (emphysema grade, EG) and measurement of the mean linear intercept (Lm). The DI depends on three components--alveolar wall/duct disruption, DId; alveolar fibrosis, DIf; and classic emphysema, DIe. DIf was a minor component in our series. The mean DI was 5.8 +/- 2.5, 10.9 +/- 3.9, and 55.7 +/- 7.0% (+/- 1 SEM) in the nonemphysematous (panel grade EG = 0), mild (0 less than EG less than or equal to 25), and moderate to severe (30 less than or equal to EG less than or equal to 60) emphysematous lungs, respectively. The increase in the DI in mild emphysema did not reach significant levels (p less than 0.2). The mean DId was 5.6 +/- 2.5, 10.0 +/- 4.0, and 12.8 +/- 3.9% in the above categories, and the DId in mild emphysema did not differ significantly from that of the nonemphysematous lungs. Lm showed a similar trend and alveolar disruption did not precede airspace enlargement, rather both changes appeared to advance in parallel. The DI correlated closely with EG (r = 0.83, p less than 0.01), but this was due to the component of DIe. The DIe increased steeply in the lungs with EG greater than or equal to 30.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2913884 TI - Surfactant phosphatidylcholine metabolism and surfactant function in preterm, ventilated lambs. AB - Preterm lambs were delivered at 138 days gestational age and ventilated for periods up to 24 h in order to study surfactant metabolism and surfactant function. The surfactant-saturated phosphatidylcholine pool in the alveolar wash was 13 +/- 4 mumol/kg and did not change from 10 min to 24 h after birth. Trace amounts of labeled natural sheep surfactant were mixed with fetal lung fluid at birth. By 24 h, 80% of the label had become lung-tissue-associated, yet there was no loss of label from phosphatidylcholine in the lungs when calculated as the sum of the lung tissue plus alveolar wash. De novo synthesized phosphatidylcholine was labeled with choline given by intravascular injection at 1 h of age. Labeled phosphatidylcholine accumulated in the lung tissue linearly to 24 h, and the labeled phosphatidylcholine moved through lamellar body to alveolar pools. The turnover time for alveolar phosphatidylcholine was estimated to be about 13 h, indicating an active metabolic pool. A less surface-active surfactant fraction recovered as a supernatant after centrifugation of the alveolar washes at 40,000 x g increased from birth to 10 min of ventilation, but no subsequent changes in the distribution of surfactant phosphatidylcholine in surfactant fractions occurred. The results were consistent with recycling pathway(s) that maintained surface-active surfactant pools in preterm ventilated lambs. PMID- 2913885 TI - Relationship between alveolar saturated phosphatidylcholine pool sizes and compliance of preterm rabbit lungs. The effect of maternal corticosteroid treatment. AB - The relationship between alveolar saturated phosphatidylcholine pool size and compliance was evaluated in control and maternal corticosteroid-treated 27-, 28-, and 29-day gestational age preterm ventilated rabbits. Surfactant pool sizes below about 0.7 mumol saturated phosphatidylcholine/kg body weight did not alter compliance in either group. Compliance increased to values comparable to surfactant-treated or term newborn rabbits over a narrow range of saturated phosphatidylcholine pool sizes from about 0.7 to 1.2 mumol/kg for corticosteroid treated rabbits and from about 0.9 to about 2.3 mumol/kg for control rabbits (p less than 0.01). When these results are compared with those from surfactant treated rabbits, almost an order of magnitude less endogenous surfactant than exogenous surfactant is needed to alter compliance in preterm ventilated rabbits. PMID- 2913886 TI - Glutathione deficiency in the epithelial lining fluid of the lower respiratory tract in idiopathic pulmonary fibrosis. AB - Glutathione (L-gamma-glutamyl-L-cysteinyl-glycine, GSH), a sulfhydryl-containing tripeptide produced by most mammalian cells, is an efficient scavenger of toxic oxidants, including hydrogen peroxide, an oxidant that plays a major role in the oxidant burden placed on the epithelial surface of the lower respiratory tract in chronic inflammatory states. GSH is present in the epithelial lining fluid of the normal lower respiratory tract, where it is thought to play a major role in providing antioxidant protection to the epithelial cells. In this regard, we hypothesized that the lower respiratory tract of patients with IPF may be chronically depleted of this antioxidant, thus leading to an increased susceptibility of lung epithelial cells to oxidant injury. To evaluate this concept, the concentration of glutathione was determined in the epithelial lining fluid of the lower respiratory tract of 15 patients with IPF and compared to that of 19 normal subjects. Strikingly, whereas ELF glutathione concentrations were high in normal subjects (429 +/- 34 microM), a fourfold decrease was found in patients with IPF (97 +/- 18 microM, p less than 0.001). In the context of the known oxidant burden present in the lower respiratory tract of patients with IPF, these observations of a "GSH deficiency" in IPF ELF suggest that there is a marked oxidant-antioxidant imbalance at the alveolar surface of these persons, thus increasing the susceptibility to the severe epithelial cell damage characteristic of this disease. PMID- 2913887 TI - 5-Hydroxytryptamine uptake in oxygen radical-mediated acute lung injury. AB - Pulmonary endothelial cell function (ECF) studies have been shown to be a sensitive indicator of chronic lung injury. We attempted to correlate changes in 5-hydroxytryptamine (5HT) uptake with an acute oxygen radical-mediated lung injury in dogs. Beta-d glucose/glucose oxidase was injected intravenously in an experimental group (n = 10), while the control group (n = 5) received saline. 5HT uptake, measured using a multiple indicator dilution technique before and 20 min after injection, was calculated for both the percent total uptake and the peak extraction ratio of 5HT during a single passage through the lung. The mean pulmonary and systemic arterial pressures (PAP, SAP), total pulmonary resistance (TPR), extravascular lung water (EVLW), and wet-to-dry weight ratios were also determined. The experimental group showed an acute rise in PAP and TPR and a fall in SAP after the injection, all returning to normal by 20 min; total 5HT uptake fell from 81 +/- 2.3% to 47 +/- 6.5% (p = 0.0002) as did the peak extraction ratio from 0.87 +/- 0.013 to 0.44 +/- 0.066 (p = 0.0001). No change in 5HT uptake was observed in the control group. EVLW did not change in either group, but wet to-dry weight ratio was elevated in the experimental group (5.21 +/- 0.12 versus 4.73 +/- 0.06, p less than 0.01). ECF studies of 5HT uptake appear to be a sensitive indicator of acute lung injury in this large-animal, oxygen radical induced injury model. PMID- 2913888 TI - Polyamines, DNA synthesis, and tolerance to hyperoxia of mice and rats. AB - Adaptation to hyperoxia has been attributed to increased activities of protective enzymes, but we suggest that an additional factor may be the lung's capacity to repair itself in hyperoxia. Such repair would require increased polyamines, but there are reports that two key enzymes of polyamine metabolism are suppressed by hyperoxia or oxidants. Because rats can adapt to hyperoxia but mice cannot, we compared their changes of polyamine metabolism and judged cell repair by using [3H]thymidine to estimate DNA synthesis. Both species developed increased ornithine decarboxylase activity and putrescine content, but the mouse did not develop increased S-adenosylmethionine decarboxylase activities or increases of spermidine and spermine as did the rat when exposed to 85% O2. Furthermore, we confirmed that the rat lung does respond to hyperoxia with increased DNA synthesis, but the mouse lung does not. The results suggest that in addition to increased activities of protective enzymes, increased repair processes in the rat lung may play a role in its capacity to adapt to hyperoxia. The incomplete response of polyamine metabolism in mice may contribute to their inability to adapt in hyperoxia. PMID- 2913889 TI - Ozone-induced inflammation in the lower airways of human subjects. AB - Although ozone (O3) has been shown to induce inflammation in the lungs of animals, very little is known about its inflammatory effects on humans. In this study, 11 healthy nonsmoking men, 18 to 35 yr of age (mean, 25.4 +/- 3.5), were exposed once to 0.4 ppm O3 and once to filtered air for 2 h with intermittent exercise. Eighteen hours later, bronchoalveolar lavage (BAL) was performed and the cells and fluid were analyzed for various indicators of inflammation. There was an 8.2-fold increase in the percentage of polymorphonuclear leukocytes (PMN) in the total cell population, and a small but significant decrease in the percentage of macrophages after exposure to O3. Immunoreactive neutrophil elastase often associated with inflammation and lung damage increased by 3.8-fold in the fluid while its activity increased 20.6-fold in the lavaged cells. A 2 fold increase in the levels of protein, albumin, and IgG suggested increased vascular permeability of the lung. Several biochemical markers that could act as chemotactic or regulatory factors in an inflammatory response were examined in the BAL fluid (BALF). The level of complement fragment C3 alpha was increased by 1.7-fold. The chemotactic leukotriene B4 was unchanged while prostaglandin E2 increased 2-fold. In contrast, three enzyme systems of phagocytes with potentially damaging effects on tissues and microbes, namely, NADPH-oxidase and the lysosomal enzymes acid phosphatase and beta-glucuronidase, were increased neither in the lavaged fluid nor cells. In addition, the amounts of fibrogenic related molecules were assessed in BALF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2913890 TI - Enhanced aerosol deposition in the lung with mild airways obstruction. AB - We investigated the sensitivity of aerosol deposition to airways obstruction by measuring total deposition fraction of inert aerosol in normal conscious sheep (n = 6) after challenging cholinergic agent, pilocarpine (PL) (0.5 mg/kg intravenously) with and without a prior challenge of beta 2-adrenergic agonist, terbutaline sulfate (TS) (0.025 mg/kg subcutaneously). Aerosol deposition was measured by a light-scattering aerosol photometer in situ while sheep rebreathed 1.0-micron-diameter inert oil droplets from a 0.2-L collapsible bag at a rate of 30 breaths/min. Total accumulated deposition at the fifth breath (AD5) as a percentage of initial aerosol concentration was determined and compared with mean pulmonary airflow resistance (RL). After PL, both AD5 and RL increased significantly from baseline values by 51 +/- 9% and 597 +/- 118% (mean +/- SE), respectively, whereas AD5 and RL decreased significantly by 16 +/- 4% and 34 +/- 6%, respectively after TS (p less than 0.05). After PL subsequent to TS (TS-PL), AD5 increased in all six sheep by 33 +/- 7% from post-TS values (p less than 0.05). However, RL did not change from post-TS values. Greater changes in RL than in AD5 after PL (bronchoconstriction) or TS (bronchodilation) suggest a greater sensitivity of RL than AD5 to airway patency in the large airways. Lack of increase of RL after TS-PL indicates that bronchoconstrictive effect of PL was blocked by prior challenge with TS. Therefore, the increase in AD5 after TS-PL may be related to the peripheral airway obstructions which might have been caused by increased secretions induced by a potent secretagogue PL.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2913891 TI - Falls in peripheral eosinophil counts parallel the late asthmatic response. AB - Peripheral eosinophil counts were measured at intervals before and after control and allergen inhalation in 14 asthmatic subjects. A relative fall in eosinophil counts was noted 9 h after allergen challenge, in contrast to the diurnal increase seen on the control day (p = 0.005). This fall in eosinophil count correlated strongly with the magnitude of the late asthmatic response (r = -0.72, p = 0.003) and with the changes in bronchial responsiveness to histamine at 3 and 24 h after allergen was given (r = 0.54, p = 0.044 and r = 0.82, p less than 0.001, respectively). The findings demonstrate eosinophil kinetics are related to the occurrence of late-phase reactions and to the associated worsening of bronchial hyperreactivity. PMID- 2913892 TI - Circadian variations in theophylline concentrations and the treatment of nocturnal asthma. AB - The nocturnal worsening of asthma is a common problem that can be difficult to treat. Two different sustained-release theophylline preparations were used to determine (1) if the serum theophylline concentrations (STC) depend on the type and dosing schedule of the preparation, (2) the relationship between STC and the circadian variations in asthma, and (3) the effect of STC on sleep quality and respiratory patterns during the night. In 16 subjects with nocturnal asthma, the STC were significantly higher during the daytime on twice-daily versus once-daily theophylline preparations given at 7 P.M., but the FEV1 values were similar. During the night, the STC were significantly higher with the once-daily regimen, and the awakening FEV1 value was also improved (p less than 0.05). All polysomnographic variables were similar between the two preparations, except that with the once-daily preparation there was a decreased number of hypopneas (p less than 0.05) and fewer minutes below an oxygen saturation of 90% (p less than 0.05). We conclude that patients with nocturnal asthma need their treatment focused on the nocturnal portion of the circadian cycle and that higher STC during this critical time period are beneficial without interfering with sleep quality. PMID- 2913893 TI - The effect of prolonged submaximal warm-up exercise on exercise-induced asthma. AB - The effect of a prolonged warm-up period of exercise on subjects with exercise induced asthma (EIA) has been studied. Seven asthmatic subjects with known EIA were exercised according to two different protocols on two separate days, which were randomized. On Day A, subjects performed a standard 6-min treadmill run (S1A), which increased heart rate to 98% predicted maximum, followed 45 min later by an identical run (S2A). Refractoriness was demonstrated on the second exercise test, with a mean maximal fall in FEV1 of 29 +/- 3.1% and a PEFR of 32 +/- 2.8% after S2A, compared with a mean maximal fall in FEV1 of 46 +/- 2.6% and a PEFR of 51 +/- 4.0% after S1A. On Day B, subjects performed a 30-min treadmill run at a lower gradient (W1B), followed 21 min later by another standard 6-min treadmill test (S2B). W1B was followed by significantly less EIA (mean maximal fall in FEV1 of 17 +/- 5.4% and a PEFR of 21 +/- 6.3%) than followed S1A. Nevertheless, when subjects subsequently performed a standard 6-min run (S2B), significant refractoriness to bronchoconstriction, comparable to that observed after S2A, developed, with a mean maximal fall in FEV1 of 26 +/- 3.6% and a PEFR of 27 +/- 2.3% (p less than 0.05). We conclude that a warm-up period of exercise can induce refractoriness to EIA without itself inducing marked bronchoconstriction. PMID- 2913894 TI - Pulmonary hemodynamics and gas exchange during exercise in liver cirrhosis. AB - We have recently shown that ventilation-perfusion (VA/Q) mismatching at rest in cirrhosis is due to an abnormal pulmonary vascular tone. It has been suggested that in patients with cirrhosis, O2 transfer might become diffusion-limited during exercise. This study examined pulmonary hemodynamics and mechanisms modulating gas exchange during exercise (60 to 70% VO2max) in six patients (41 +/ 5 yr, mean +/- SEM) with cirrhosis but with normal lung function tests. At rest, QT was high (8.4 +/- 0.5 L/min), pulmonary vascular resistance (PVR) was low (0.61 +/- 0.17 mm Hg/L/min), and there was mild to moderate VA/Q mismatching (LogSD Q, 0.79 +/- 0.09; normal range, 0.3 to 0.6). However, hyperventilation (PaCO2, 29 +/- 2 mm Hg) and high QT (thus, high PVO2, 41 +/- 2 mm Hg) contributed to the maintenance of PaO2 within normal values (99 +/- 7 mm Hg). Exercise VO2 (1,278 +/- 122 ml/min) was normal relative to work load, but, contrary to that in normal subjects, QT was higher and PVR did not fall. During exercise, PaO2 showed a trend to decrease (to 90 +/- 5 mm Hg) and PaCO2 to rise (to 35 +/- 2 mm Hg), but the differences failed to reach statistical significance (p = 0.07 each). PVO2 fell significantly with exercise (41 +/- 2 to 33 +/- 0.3 mm Hg, p less than 0.05), but neither AaPO2 (15 +/- 7 to 21 +/- 6 mm Hg) nor VA/Q inequality (LogSD Q, 0.82 +/- 0.11) changed. No systemic difference was noticed between predicted and measured PaO2 values, suggesting no O2 diffusion impairment during exercise.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2913895 TI - Tannin induces endothelium-dependent contraction and relaxation of rabbit pulmonary artery. AB - The effects of tannin purified from cotton bracts were studied on pulmonary artery rings isolated from rabbit lungs. Tannin (2 to 50 micrograms/ml) caused concentration-dependent contractions of resting vessels, and maximal responses averaged 25% of the contraction induced by 10(-4) M exogenous norepinephrine. Tannin-induced contractions were blocked by removal of the endothelium and by pretreatment of intact tissues with either indomethacin or SQ 29,548, a thromboxane A2 receptor antagonist. In contrast, tissues contracted with 3 x 10( 7) M norepinephrine relaxed by 49 +/- 8% in response to 50 micrograms/ml tannin. Tannin-induced relaxations were unaltered by pretreatment of tissues with indomethacin but were significantly reduced by pretreatment with hemoglobin. We conclude that tannin causes the release of both smooth muscle contracting and relaxing factors from pulmonary artery endothelial cells. Thromboxane A2 is the contracting factor, whereas an endothelium-derived relaxing factor such as nitric oxide appears to be the primary relaxing factor that is released. PMID- 2913896 TI - Cardiopulmonary effects of high frequency positive-pressure ventilation versus jet ventilation in respiratory failure. AB - Conventional ventilators are frequently used at high rates in the intensive care nursery to achieve adequate oxygenation and ventilation with reduced peak inspiratory pressure. The efficacy and limitations of high frequency positive pressure ventilation (HFPPV) using a conventional ventilator were studied by comparing the cardiopulmonary effects of HFPPV with those of high frequency jet ventilation (HFJV) in an animal model of respiratory failure. Sixteen saline lavaged rabbits were ventilated with either HFPPV or HFJV for 2 h using rates of 200 breaths/min, inspiratory to expiratory ratio of 1:2, and FIO2 of 1.0. As controls an additional eight lavaged rabbits were ventilated at conventional rates (40 to 60 breaths/min). Proximal peak inspiratory pressure as indicated on the ventilator manometer or drive pressure was adjusted to maintain acceptable blood gases. Cardiac output (CO) was measured by thermodilution. Although there was a significant decrease in cardiac function over time, there were no significant differences between the groups in CO or stroke volume. Satisfactory oxygenation and ventilation were maintained in all groups. Static respiratory system compliance and mean airway pressure were similar among the groups. Histologic examination of the lungs revealed no differences between the three ventilator groups. The results of this study indicate that both HFPPV and HFJV are effective in short-term maintenance of normal blood gases in respiratory failure without any discernable differences in their effects on cardiovascular function. At very high rates, however, increases in VT are not possible with HFPPV, which limits its usefulness and flexibility in respiratory failure. PMID- 2913897 TI - Effects of acute hyperinflation on the mechanical effectiveness of the parasternal intercostals. AB - We studied the mechanical effectiveness of the parasternal intercostals at FRC and near TLC in 14 supine, vagotomized, and anesthetized dogs. First, we determined the relationship between parasternal intramuscular pressure (Pps), measured with Gaeltec 12 CT-mini-transducers, and parasternal EMG activity (Eps) during breathing at FRC and near TLC. Second, we examined the changes in Pps and the changes in parasternal force (Fps) generated during bilateral parasternal stimulation at FRC and near TLC with a given supramaximal stimulus. Before phrenicotomy, the inspiratory increases in Pps remained relatively constant near TLC (FRC, 50.4 +/- 16.5 versus TLC, 48.7 +/- 13.3 cm H2O, NS), whereas the Eps clearly decreased (82.9 +/- 5.5% FRC, p less than 0.01). This indicates that the gain converting electrical activity into pressure for the parasternals is greater near TLC than at FRC. A similar pattern of changes in Pps and in Eps was observed during quiet inspiration at FRC and near TLC after phrenicotomy. During bilateral parasternal stimulation the increases in Pps near TLC tended to be greater than those at FRC (140.7 +/- 28.6 versus 100 +/- 28.3 cm H2O, NS), whereas the increases in Fps were significantly greater near TLC than at FRC (277.4 +/- 60.6 versus 214.2 +/- 47.1 g, p less than 0.05). Therefore, we conclude that the mechanical effectiveness of the parasternal contraction near TLC remains relatively unchanged and is even greater in relation to that at FRC. PMID- 2913898 TI - Reversible respiratory muscle weakness in hyperthyroidism. AB - Breathlessness is a common complaint in patients with hyperthyroidism, and respiratory failure requiring artificial ventilation, although rare, can occur. While a proximal myopathy is frequently recognized, diaphragm muscle function has not hitherto been studied in detail in thyrotoxicosis. The strength of the quadriceps femoris and respiratory muscles was therefore assessed in seven consecutive thyrotoxic patients, on presentation and during medical treatment, when euthyroid. Prior to therapy, reduced quadriceps muscle strength, vital capacity, and global expiratory and inspiratory muscle strength were found. Diaphragmatic weakness was present in one of four patients studied by measuring transdiaphragmatic pressures during maximal sniffs and during bilateral phrenic nerve stimulation at 1 Hz (twitch). After treatment, significant improvement occurred in quadriceps muscle strength, vital capacity, and global respiratory muscle strength. Sniff and twitch transdiaphragmatic pressures also increased significantly. These results indicate that respiratory muscle weakness occurs in hyperthyroidism and that such weakness is reversible with medical treatment. It is important to realize that respiratory muscles may be directly affected when assessing thyrotoxic patients with breathlessness, as severe involvement of the respiratory muscles may cause respiratory failure. PMID- 2913899 TI - Quantitative bacterial cultures of bronchoalveolar lavage fluids and protected brush catheter specimens from normal subjects. AB - Bronchoalveolar lavage (BAL) is quite useful in the diagnosis of nonbacterial lung infections, especially in immunocompromised patients, and recent studies have suggested that BAL may be useful in the diagnosis of bacterial pneumonia as well. Because previous studies indicated that bronchoscopic aspirates are usually contaminated by oropharyngeal flora, we anticipated that BAL fluid would also likely be contaminated. Therefore, the purpose of this study was to perform quantitative bacterial cultures on BAL fluids obtained from eight normal subjects. Prior to each procedure, saline was aspirated through the bronchoscope and submitted for culture. A protected brush catheter (PBC) specimen was obtained from each subject's right middle lobe, and then a BAL specimen was obtained from the same location. All specimens were quantitatively cultured for aerobic and anaerobic organisms. In addition, lidocaine concentrations were measured in the BAL fluids and the PBC specimens. Six of the eight bronchoscope cultures were sterile. Seven of the eight PBC specimens were sterile and one yielded less than 10(3) cfu/ml of normal oropharyngeal flora. One BAL fluid specimen was sterile and seven yielded from one to four bacterial strains each; however, quantitation revealed less than 10(4) cfu/ml in all specimens. Lidocaine concentrations (mean +/- 1 SD) were as follows: PBC specimen, 0.81 microgram/ml (+/- 0.62); BAL fluid specimen, 62.6 micrograms/ml (+/- 43). We conclude that BAL fluid obtained from normal subjects is frequently contaminated by oropharyngeal bacterial flora.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2913900 TI - Clinical and laboratory features of acute sulfur dioxide inhalation poisoning: two-year follow-up. AB - We present clinical and laboratory results (including nuclear imaging) obtained over a period of two years in two nonsmoking miners who were exposed to high concentrations of sulfur dioxide (SO2) after a mine explosion. Within 3 wk of the accident, both miners had evidence of severe airways obstruction, hypoxemia, markedly reduced exercise tolerance, ventilation-perfusion mismatch, and evidence of active inflammation as documented by positive gallium lung scan. Serial ventilation-perfusion scans over the first 12 months showed progressive improvement without returning to normal. After the initial recovery, there has been no significant change over the subsequent two years postinjury. Pulmonary function and exercise tests also displayed a similar pattern of initial improvement. We conclude that (1) acute exposure to high concentrations of SO2 results in severe airways obstruction, (2) pulmonary function abnormalities are partially reversible, and (3) most of the improvement occurs within 12 months after the initial injury. PMID- 2913901 TI - Early and late-phase bronchoconstriction after allergen challenge of nonanesthetized guinea pigs. PMID- 2913902 TI - Fatal respiratory syncytial virus pneumonitis in a previously healthy child. PMID- 2913903 TI - Gastroscopic screening of the post-gastrectomy stomach. Relationship of dysplasia to remnant cancer. AB - In July 1980, an aggressive screening program for benign disease of the stomach in 163 patients at risk for carcinomatous change of the gastric remnant was instituted. All patients were at least ten years post-gastrectomy. Three gastric remnant cancers were identified during esophago-gastroduodenostomy (EGD) on 45 patients undergoing only one screening endoscopic examination during the study. One hundred and eighteen additional patients underwent two or more screening gastroscopic studies between July 1980 and July 1985. Of this group, seven patients (5.8%) had gastric biopsies showing mild to moderate dysplasia in the gastric remnant. During the period July 1985 to July 1987, these seven patients underwent two to four additional gastroscopic examinations that revealed carcinoma of the gastric remnant in two patients (28%) with progression of the dysplastic changes in three of these seven patients (42%). The post-gastrectomy interval in these seven patients ranged from 10 to 27 years with a mean of 21.5 years. This study supports the concept of neoplastic change in the gastric remnant as a function of time from initial gastric resection. EGD and biopsy are important in identifying dysplastic changes which may be harbingers of invasive carcinoma of the gastric remnant. Aggressive endoscopic screening is recommended for patients with dysplasia in order to identify gastric remnant cancer while potentially curable. PMID- 2913904 TI - Hepatico-jejuno-duodenostomy reconstruction following excision of choledochal cysts in children. AB - Ten children with choledochal cysts were treated at Children's Memorial Hospital in Chicago between 1979 and 1980 and at Henrietta Egleston Hospital for Children or Grady Memorial Hospital in Atlanta between 1980 and 1987. Age at the time of operation ranged from one to 46 months. There were eight girls and two boys with Type I choledochal cysts. One child with a dilated but histologically normal common bile duct underwent a choledochoduodenostomy. The remaining nine patients had excision of the choledochal cyst. Continuity with the GI tract was then re established with a valved isolated jejunal segment interposed between the common hepatic duct and the duodenum. The valve serves to prevent reflux of enteric contents up into the biliary tract. The short jejunal segment allows bile to drain into the duodenum with minimal stasis; this more closely approximates the natural physiologic state than does a Roux-en-Y reconstruction. There was no mortality, with follow up ranging from six months to over eight years. Two post operative complications (one anastomotic stricture and one small bowel obstruction) occurred, both in the same patient. There were no anastomotic leaks and no episodes of post-operative cholangitis. All patients are currently free of jaundice and none have signs of portal hypertension. The treatment of choledochal cysts is excision. Biliary tract reconstruction with the valved common hepatico jejuno-duodenostomy is safe, effective, and physiologically appealing. PMID- 2913905 TI - Distal pancreatectomy with and without splenectomy. A comparative study. AB - Twenty-one patients undergoing distal pancreatectomy from January 1980 through April 1987 were studied retrospectively. Group I (n = 10) had distal pancreatectomy with splenectomy, and Group II (n = 11) had distal pancreatectomy with splenic preservation. The groups were comparable in mean age and extent of pancreatic resection. Operative time in Group I patients who did not require additional major procedures was 3.74 +/- 1.01 hours, compared with 2.86 +/- 1.68 hours for similar Group II patients. The overall complication rate in Group I was 40 per cent, including two pancreatic fistulas, one subphrenic abscess, and one gastric fistula. In Group II the overall complication rate was 36.4 per cent, with one pancreatic fistula, one subphrenic abscess, and one colonic fistula. Splenic infarction occurred in only one patient (Group II), in whom both splenic vessels were ligated. No patient developed insulin-dependent diabetes. There were no deaths. The mean hospitalization time was 18.8 days in Group I, and 17.5 days in Group II. Splenectomy should not be considered a routine part of distal pancreatic resection. Splenic preservation can be achieved in selected cases with no increase in complication rate, operative time, or length of postoperative hospitalization. PMID- 2913906 TI - Pseudo-pseudo-obstruction. A clinically relevant concept. AB - Four patients with small bowel obstruction were treated nonoperatively after being misdiagnosed as chronic idiopathic intestinal pseudo-obstruction. Three patients with pseudo-pseudo-obstruction developed significant morbidity, and one patient died while being treated medically. Differentiation between pseudo obstruction and mechanical obstruction can be difficult and may require laparotomy to establish the diagnosis. Intestinal manometry suggested a mechanical cause for obstruction in two patients and should be done in all patients that carry the diagnosis of intestinal pseudo-obstruction. Other clues to the diagnosis of intestinal pseudo-obstruction are discussed. Intestinal pseudo-obstruction is an uncommon disease that should not be a diagnosis of exclusion but should be diagnosed using historical, radiographic, manometric, pathologic, and operative data. PMID- 2913907 TI - Xanthogranulomatous cholecystitis. A clinical and pathologic study of twelve cases. AB - Xanthogranulomatous cholecystitis often presents as a severe chronic cholecystitis associated with abdominal pain, fever, and leukocytosis. Gallstones are present in most cases. At operation, there are adhesions to surrounding tissues, and sometimes a mass is found, mimicking tumor of the gallbladder. The gross and microscopic appearances are characteristic with multiple intramural nodules composed of foamy histiocytes and inflammatory cells. Cholesterol contents of these nodules are high. Involvement of the Rokitansky-Aschoff sinuses with liberation of bile lipids into the adjacent tissue is implicated in the pathogenesis of this lesion. PMID- 2913908 TI - Abdominal candidiasis in surgical patients. AB - Although abdominal candidiasis in critically ill surgical patients is becoming increasingly common, optimal management has not been defined. We treated 16 patients with abdominal candidiasis over a 36 month period. Violation of the gastrointestinal tract mucosa was the most common precipitating event (13 patients). Predisposing factors included: CVP catheters, broad spectrum antibiotics, and parenteral hyperalimentation in all patients, H2 blockers/antacids in 14 patients, as well as malnutrition (7 patients), DM (3 patients), alcoholism (3 patients), and steroids/chemotherapy (3 patients). Candida was isolated from an abscess in seven patients, peritoneal fluid in six patients and both in three patients. In four patients abdominal candidiasis was preceded by positive cultures from blood or two peripheral sites which had not been treated. All patients were treated with amphotericin B (146-4000 mg) without any major adverse effects. Fungal infection was eradicated in ten patients; three patients succumbed to candidiasis. Patients treated within seven days required less Amphotericin B and appeared to have a better outcome than those having delayed treatment. The authors conclude that abdominal candidiasis is a potentially lethal infection in critically ill surgical patients that should be aggressively treated. Amphotericin B can be safely administered and concurrent antibiotics need not be stopped. PMID- 2913909 TI - Gastrointestinal disconnection and the treatment of intra-abdominal sepsis. AB - Current operative treatment for intra-abdominal sepsis secondary to internal gastrointestinal fistulas is aimed at wide drainage of septic foci and elimination of continued peritoneal soilage. Although methods for surgical drainage of abscesses and fistulous tracts are well established, the optimal method for surgical prevention of continued peritoneal soilage remains controversial. The authors applied the principle of complete gastrointestinal disconnection and performed diversion of the gastrointestinal tract and tube decompression proximal to the fistulous opening in the treatment of 22 critically ill patients with intra-abdominal sepsis from gastric or small bowel fistulas. Patient survival varied according to the level of the site of gastrointestinal leakage. All patients (5 out of 5) who had leakage in the distal small bowel survived. Six of nine (66%) patients with leakage from the proximal jejunum and six of eight (75%) of patients with gastroduodenal leakage survived. The overall survival rate of 77 per cent observed in this group of patients supports the authors' hypothesis that complete gastrointestinal disconnection is a valuable adjunct in the treatment of these severely ill patients. PMID- 2913910 TI - Factors affecting mortality in patients operated upon for complications of peptic ulcer disease. AB - Surgical treatment of complicated peptic ulcer disease (PUD) is associated with a high mortality in selected, high-risk patients. The authors reviewed their operative experience for PUD over a five year period beginning in July 1982. One hundred and sixty-two operative procedures were performed on 160 patients. The indications for surgery were intractability (18); perforation (50); hemorrhage (81); and obstruction (13). The average ages of the survivors and those who died was 49.0 and 65.7 years respectively. Partial gastric resection (PGR), with or without vagotomy, was the most commonly performed procedure (54% of cases) while vagotomy and drainage (V & D) was used in 31 per cent of patients. The overall mortality in this series was 8 per cent; it was highest in the hemorrhage group (10%). Pre-operative transfusion requirements in this population were greater in those who died versus those who survived (12.1 and 7.3 units respectively, P less than 0.005). In addition, 75 per cent of the deaths were over 60 years of age. In elderly patients operated upon for hemorrhage, the procedure-related mortality for V & D and PGR was 24 per cent and 13 per cent respectively. (These groups were similar with regard to co-morbidity, hemodynamic stability, and transfusion requirements). It is the authors contention that PGR may be safely used for the treatment of bleeding peptic ulcer disease (particularly GU) in selected elderly, high-risk patients. PMID- 2913911 TI - Metastatic colon carcinoma to the biliary tract mimicking choledocholithiasis. AB - This case is reported because of its rarity and in order to demonstrate that, using ERCP, it can be difficult at times to differentiate not only primary from metastatic diseases of the common duct, but also both of these malignant conditions from benign choledocholithiasis. PMID- 2913912 TI - Polypropylene mesh closure of infected abdominal wounds. AB - The management of extensive abdominal tissue loss in the presence of intraabdominal infection or wound dehiscence challenges the surgeon's ingenuity in wound care. Radical debridement and primary fascial closure may be impossible due to tissue loss or extensive bowel edema. The use of a synthetic mesh to bridge the fascial defect and maintain the integrity of the abdominal cavity may initially appear to be an attractive alternative to simply leaving the viscera exposed. However, this report and review of the literature document the frequent complications and high morbidity associated with this technique. An overall complication rate approaching 80% can be anticipated if polypropylene mesh is used in this emergency situation. Two modifications of wound care appear to markedly diminish the incidence of serious complications. Covering the mesh with full-thickness skin or muscle flaps in the early postoperative period, or removing the mesh at the earliest time conducive to fascial closure (within 2 weeks) reduced the overall complication rate from 55% to 15% in this review. However, it is often impossible to predict which patients will be amenable to early mesh removal, and full-thickness coverage of a persistently infected wound is usually doomed to failure. Despite the occasional usefulness of these modifications, this review suggests that polypropylene mesh in the emergency setting has an unacceptably high complication rate, and alternative methods of wound care in these complex situations should be considered. PMID- 2913913 TI - Self-report questionnaire scores in rheumatoid arthritis compared with traditional physical, radiographic, and laboratory measures. AB - STUDY OBJECTIVE: To assess whether scores on a simple self-report questionnaire to depict the clinical status of patients with rheumatoid arthritis are correlated with traditional measures of physical, radiographic, laboratory, functional, and global status. DESIGN: The self-report questionnaire was administered at the same time the following variables were assessed: American Rheumatism Association functional class, joint count, hand radiograph, erythrocyte sedimentation rate, rheumatoid factor titer, walking time, grip strength, button test, and global self-assessment. SETTING: University rheumatology clinic, the rheumatology clinic of a Veterans Administration hospital, and a private rheumatology practice. PATIENTS: The study included 259 patients who met the criteria of the American Rheumatism Association for a diagnosis of definite or classic rheumatoid arthritis. INTERVENTIONS: Standard rheumatologic care for patients with rheumatoid arthritis. MEASUREMENTS AND MAIN RESULTS: Self-report questionnaire scores were significantly correlated with the joint count, radiographic score, erythrocyte sedimentation rate, grip strength, button test, walking time, American Rheumatism Association functional class, and global self-assessment. Patients were categorized into five questionnaire score categories of 1.00, indicating no dysfunction, and 1.01 to 1.50, 1.51 to 2.00, 2.01 to 3.00, and 3.01 to 4.00, indicating progressive dysfunction. In these five categories, more than ten involved joints were seen in 11%, 37%, 67%, 79%, and 100% of patients, respectively, and erythrocyte sedimentation rates greater than 20 mm/h in 29%, 49%, 64%, 74%, and 85% of patients, respectively. Similar results were seen for other physical and radiographic measures. The questionnaire score was as effective in explaining other measures of clinical status as was any other available measure. CONCLUSIONS: A simple self-report questionnaire provides information similar to many traditional measures in rheumatoid arthritis and appears to be an attractive, cost-effective approach to assessing and monitoring quantitatively the status of an individual patient. PMID- 2913914 TI - Calcitriol treatment is not effective in postmenopausal osteoporosis. AB - STUDY OBJECTIVE: To determine if calcitriol is an effective treatment in postmenopausal osteoporosis. DESIGN: Double-blind, randomized clinical trial of 2 years' duration. SETTING: University medical center with patients recruited by media announcements. PATIENTS: Eighty-six postmenopausal women with vertebral compression fractures. INTERVENTIONS: Patients were treated with calcitriol or placebo. Mean dose was 0.43 micrograms/d. Dietary calcium was 1000 mg/d (24.9 mmol/d). The medication dose and dietary calcium were adjusted for hypercalciuria or hypercalcemia. MEASUREMENTS AND MAIN RESULTS: No significant differences between placebo and control groups were seen in the percent change in total body calcium (0.4% +/- 1.0 compared with 0.0% +/- 0.9), single photon absorptiometry ( 0.5% +/- 1.2 compared with -3.1% +/- 0.9) or dual photon absorptiometry (0.0% +/- 1.7 compared with -1.0% +/- 2.2). New fractures were seen in 16% of the placebo group and 26% of the calcitriol groups, so the difference in percent fractures was 10% (95% CI, -5.7% to 25.7%). Bone biopsies did not show changes in either group. The calcitriol group had significantly higher serum and urine calcium values, but renal function was not worse than in the placebo group. CONCLUSIONS: Calcitriol is not an effective treatment for established postmenopausal osteoporosis. PMID- 2913916 TI - The histologic diagnosis of myocarditis. PMID- 2913915 TI - Diagnosis of sulfonamide hypersensitivity reactions by in-vitro "rechallenge" with hydroxylamine metabolites. AB - STUDY OBJECTIVE: To determine whether differences in in-vitro detoxification of sulfonamide-reactive metabolites can be detected among the lymphocytes from controls, patients with sulfonamide hypersensitivity reactions, and patients with nonhypersensitivity reactions to the sulfonamide agents. DESIGN: In-vitro toxicity assay on lymphocytes. SETTING: Clinics for adverse drug reactions in an adult and pediatric tertiary care center. PATIENTS: Peripheral blood lymphocytes were obtained from 46 normal volunteers and 76 patients referred to the clinic for assessment of adverse drug reactions to sulfonamide agents. Thirty-one patients had clinical histories consistent with a diagnosis of hypersensitivity reaction, whereas 45 patients had clinical histories felt to be inconsistent with a diagnosis of hypersensitivity reaction. INTERVENTIONS: Lymphocytes were assayed with tetrazolium to determine toxicity from the hydroxylamine of sulfamethoxazole. MEASUREMENTS AND MAIN RESULTS: The lymphocytes from patients with a history of hypersensitivity reactions showed markedly increased toxicity across a tenfold-concentration toxicity-concentration curve compared with those from controls and patients with a history of nonhypersensitivity reactions. These differences were highly significant (P less than 0.01). No difference was found between the toxicity shown by the lymphocytes from controls and that shown by the lymphocytes from patients with a history of nonhypersensitivity reactions. CONCLUSIONS: Metabolic differences in the production and detoxification of reactive metabolites of sulfonamide agents are important determinants of hypersensitivity reactions to these agents. These results suggest that the hydroxylamine derivative of sulfamethoxazole may be a reactive metabolite mediating these reactions. Sulfonamide hydroxylamines are useful in the diagnosis and study of the pathogenesis of hypersensitivity reactions to sulfonamide agents. PMID- 2913917 TI - A subclavian bruit in the thoracic outlet syndrome. PMID- 2913918 TI - Rimantadine and seizures. PMID- 2913919 TI - Large-volume paracentesis in outpatients. PMID- 2913920 TI - Exacerbation of hypercalcemia after needle biopsy of a parathyroid cyst. PMID- 2913922 TI - Transposition of the abdominal viscera and "nonvisualization of the gallbladder". PMID- 2913921 TI - Diltiazem and thrombocytopenia. PMID- 2913923 TI - APACHE: a nonproprietary measure of severity of illness. PMID- 2913924 TI - Phenotypic heterogeneity in familial Alzheimer's disease: a study of 24 kindreds. AB - We report the clinical and neuropathological characteristics occurring in 180 demented individuals from 24 kindreds with familial Alzheimer's disease (FAD). Each family had at least two affected generations, and at least one autopsy or brain biopsy was compatible with the diagnosis of AD. Forty-nine neuropathological specimens or reports were reviewed. Mean age of onset for the total group was 54.7 years +/- 11.5, with a large range of 30 to 84 years. Mean age at death was 63.5 years +/- 12.2, with a range of 46 to 85. Mean duration of disease was 8.8 years +/- 4.4, with a range of 1 to 23 years. Six findings suggested phenotypic heterogeneity in FAD. (1) Five families represented an early age of onset group with mean onset at 42 years (range 30 to 51 years) and mean disease duration of 6.7 years. (2) Eight families represented a late onset group with mean onset at 68 years (range 59 to 78 years) and a mean duration of 8.5 years. (3) Seven families were of Volga German ancestry, all originating from the same two villages in Russia. Mean age of onset was 55.9 years (range 40 to 72 years), with a mean disease duration of 10 years. This group probably represents the genetic founder effect of an autosomal dominant gene for AD. (4) One family had the unusual characteristics of neurofibrillary tangles and granulovacuolar change but no amyloid plaques, a mean disease duration of more than 11 years, and a "schizophrenia-like" onset. (5) One family with late onset also had clinical and pathological evidence for anterior horn cell disease. (6) Two autopsies in 1 family both showed remarkable rarefaction of myelin and expansion of perivascular spaces in centrum semiovale (etat crible), with marked leptomeningeal and cortical amyloid angiopathy, distinct from the other FAD brains. It remains to be determined whether the clinical and pathological differences between these families represent genetic heterogeneity at the biochemical or molecular level. PMID- 2913925 TI - Metabolic changes in rabbit spinal cord after trauma: magnetic resonance spectroscopy studies. AB - Combined phosphorus and proton magnetic resonance spectroscopy (MRS), using double-tuned surface coils, was used to monitor certain metabolic changes in the L-3 spinal segment of anesthetized rabbits prior to and following experimental spinal cord trauma. Following severe trauma, resulting in spastic paraplegia, there was a delayed and progressive accumulation of lactic acid, a decline in intracellular pH, and a loss of high-energy phosphates. Maximal alterations occurred between 2 and 3 hours after the trauma, with little further change by 4 hours. Histological examination 2 weeks after trauma showed tissue necrosis and cavitation. These findings support the concept of secondary tissue injury after spinal cord trauma and suggest that early changes in metabolism, as shown by MRS, may predict irreversible tissue damage. PMID- 2913926 TI - Intraventricular hemorrhage in the premature infant--current concepts. Part I. AB - Although the incidence of periventricular-intraventricular hemorrhage (IVH) has decreased in recent years, the increasing survival rates for the smallest premature infants indicate that the lesion will continue to be a major problem in neonatal intensive care facilities. The neuropathology is characterized by an elemental lesion, bleeding into the subependymal germinal matrix, with subsequent rupture into the lateral ventricle. Important neuropathological consequences are germinal matrix destruction, posthemorrhagic hydrocephalus, and periventricular hemorrhagic infarction. The last of these appears to be a venous infarction and is a critical determinant of neurological outcome. Neuropathological accompaniments, not caused by the IVH, include periventricular leukomalacia and pontine neuronal necrosis. The pathogenesis of IVHs is related to intravascular, vascular, and extravascular factors. Intravascular factors involve primarily control of blood flow and pressure in the microcirculation of the germinal matrix. Particular pathogenetic importance can be attached to fluctuations in cerebral blood flow, abrupt increases in flow, decreases in flow with injury to matrix vessels, increases in cerebral venous pressure, and, in selected infants, disturbances of platelet function and coagulation. Vascular factors relate to the microcirculation of the matrix, the site of the initial bleeding. A maturation dependent alteration in vascular integrity and a vulnerability of matrix vessels to ischemic injury appear important. Extravascular factors include those relevant to mesenchymal and glial support for matrix vessels and to local fibrinolytic activity in the germinal matrix. The latter may be a manifestation of the proteolytic activity now recognized to be of general importance in developmental remodeling of the mammalian central nervous system. PMID- 2913927 TI - Stretch reflex dynamics in spastic elbow flexor muscles. AB - Previous studies of stretch reflexes in patients with spastic hypertonia have emphasized the dynamic character of stretch reflex output. In contrast, our own studies of stretch reflex dynamics in spastic elbow flexor muscles of 14 hemiparetic human subjects have shown that stretch-evoked torque displays a relatively weak dependence on stretch velocity, and there is generally no preferential enhancement of dynamic as compared with static reflex output. Moreover, stretch reflex dynamics are broadly similar in voluntarily activated spastic and normal elbow flexor muscles. These findings support our hypothesis that spastic hypertonia results primarily from a decrease in stretch reflex threshold. The strong velocity dependence of stretch-evoked electromyographic activity in initially inactive spastic muscles could be due to a decrease in reflex threshold with increasing stretch velocity, rather than an abnormal velocity-dependent increase in stretch reflex responsiveness. PMID- 2913928 TI - Serial magnetic resonance scanning in multiple sclerosis: a second prospective study in relapsing patients. AB - A prospective study of serial magnetic resonance (MR) scans of the brain was carried out every 2 weeks for 4 to 6 months in 9 patients with mild, clinically definite, relapsing/remitting multiple sclerosis (MS). Six of the 9 patients developed a total of 12 asymptomatic new lesions in various parts of the brain. In none of the patients were the changes on MR scan accompanied by relevant new neurological symptoms or signs. New MR lesions had a characteristic temporal profile, reaching a maximum size in approximately 4 weeks before gradually shrinking, usually leaving a small residual abnormality indistinguishable from chronic MS lesions. The frequent occurrence of new asymptomatic lesions indicates that MS may be a more active process even in mildly affected asymptomatic patients than has been previously realized. The results emphasize the potential importance of using MR scanning to measure disease activity in laboratory studies of MS and in the assessment of treatment, particularly in asymptomatic patients in the early stages. We suggest that the expanding and contracting new lesions are the basic or primary lesion in MS, that the characteristic demyelinated plaque is represented by the small residual area that these lesions shrink down to, and that the typical collection of scattered white matter lesions in chronic MS may represent the accumulated residua of dozens or more of these active lesions occurring over many years. PMID- 2913929 TI - Cerebrospinal fluid biogenic amines and biopterin in Rett syndrome. AB - We evaluated cerebrospinal fluid biogenic amine metabolites in 32 patients with Rett syndrome. Significant reductions were noted in the metabolites of norepinephrine, dopamine, and serotonin, as compared with controls of similar age (p less than 0.001, p less than 0.001, and p less than 0.05, respectively). Tetrahydrobiopterin is an essential cofactor and may be rate-limiting for the synthesis of catecholamines and serotonin. Accordingly, total cerebrospinal fluid biopterin was measured and found to be elevated in patients compared with controls (p less than 0.002). These findings constitute the only biochemical changes detected in Rett syndromes so far. PMID- 2913930 TI - A comparison of somatosensory evoked and motor evoked potentials in stroke. AB - Nineteen patients with radiologically confirmed stroke, and varying degrees of hemiparesis, were studied using somatosensory evoked potentials and the recently developed technique of transcutaneous motor cortex stimulation. The functional deficit caused by stroke was assessed at the time of evoked potential testing and again on follow-up 2 months after stroke. Stroke location and degree of recovery were compared with the evoked potentials elicited an average of 8 days after the acute event. The motor response was better (p less than 0.01) than somatosensory response at predicting an outcome in terms of functional recovery, both overall and when comparing patients with similar degrees of weakness. Normal somatosensory evoked potentials also predicted recovery but were not as sensitive as the motor evoked potentials (0.01 less than p less than 0.05). Motor evoked potentials in conjunction with clinical assessment may offer a means of more accurately predicting functional outcome following stroke than can be achieved with clinical assessment, with or without somatosensory evoked potentials. The additional finding that cortically evoked motor evoked potentials were delayed only by subcortical lesions is of interest and may extend the understanding of the pathophysiological mechanism of this response in humans. PMID- 2913931 TI - Benign versus chronic progressive multiple sclerosis: magnetic resonance imaging features. AB - The extent of disease as detected by magnetic resonance imaging was compared between 32 patients with benign multiple sclerosis (MS) and 32 patients with the chronic progressive form matched for age, sex, and disease duration. Computer assisted quantitation of magnetic resonance images revealed a higher mean lesion load in chronic progressive multiple sclerosis (CPMS); however, in approximately 20% of benign MS patients the lesion load was higher than that in the CPMS patients. CPMS patients had a higher number of infratentorial lesions, yet similar numbers of supratentorial lesions, when compared with benign MS patients. The degree of confluency of lesions and the clinical expression of infratentorial lesions were typically higher in the CPMS patients. Benign MS was characterized by a lower degree of confluency and a higher number of asymptomatic infratentorial lesions. Thus, magnetic resonance imaging shows characteristic differences in magnetic resonance-detected changes between MS patients with different clinical courses. PMID- 2913932 TI - Speech manifestations in lateralization of temporal lobe seizures. AB - To evaluate the role of speech manifestations in lateralization of temporal lobe seizures, we reviewed videotapes of 100 complex partial seizures in 35 patients who underwent temporal lobectomy for intractable epilepsy. All patients had prolonged electroencephalographic video monitoring with scalp and subdural electrodes, and their speech dominance was determined with an intracarotid amobarbital test. Speech manifestations were observed in 79 seizures and were classified as vocalization, normal speech, or abnormal speech. Vocalization of sounds without speech quality occurred ictally in 48.5% of patients. Normal speech (identifiable speech) occurred ictally in 34.2% of patients. Abnormal speech (speech arrest, dysphasia, dysarthria, and nonidentifiable speech) occurred in 51.4% of patients, either ictally or postictally. Of all the above speech manifestations, only postictal dysphasia and ictal identifiable speech had significant lateralizing value: 92% of patients with postictal dysphasia had their seizures originating from the dominant temporal lobe (p less than 0.001), and 83% of those with ictal identifiable speech had their seizures from the nondominant side (p = 0.013). This study shows that speech manifestations are common in complex partial seizures of temporal lobe origin and can provide an excellent clinical tool for lateralization of seizure onset. PMID- 2913933 TI - Chemotherapy for malignant gliomas? Committee on Health Care Issues, American Neurological Association. PMID- 2913934 TI - Bilateral opercular polymicrogyria. AB - Foix-Chavany-Marie syndrome (FCMS), or faciopharyngoglossomasticatory diplegia, is an uncommon syndrome that can result from vascular or developmental lesions of the anterior opercula bilaterally. We report the first pathological documentation of the developmental form of this disorder. Pathological examination revealed bilateral failure of opercular closure, opercular polymicrogyria, periventricular gray-matter heterotopias, and absence of the septum pellucidum. PMID- 2913935 TI - The prevalence of primary Sjogren's syndrome in a multiple sclerosis population. AB - A central nervous system illness closely resembling multiple sclerosis has been described in patients with primary Sjogren's syndrome. From these reports, the estimated prevalence of this syndrome could be similar to that of multiple sclerosis in a high-frequency area. We evaluated 192 consecutive patients in our multiple sclerosis clinic to determine if such cases had gone unrecognized. We did not find any patients with clinical or serological evidence of primary Sjogren's syndrome. We conclude that it is rare for neurological manifestations of Sjogren's syndrome to mimic multiple sclerosis in our population. PMID- 2913936 TI - Patterns of serum IgM antibodies to GM1 and GD1a gangliosides in amyotrophic lateral sclerosis. AB - We studied the incidence and clinical correlates of serum antibodies to GM1 and GD1a gangliosides in patients with classical amyotrophic lateral sclerosis (ALS) and other "motor nerve" syndromes. Serum antibodies to GM1 and GD1a gangliosides were measured using enzyme-linked immunosorbent assays. Our results showed that polyclonal immunoglobulin M (IgM) antibodies to the GM1 or GD1a ganglioside or both were present at serum dilutions of 1:25 to 1:4,000 in 78% (57/73) of patients with ALS. Only 8% of normal controls had similar antibodies. The pattern of serum antibody reactivity correlated with the pattern of clinical involvement in our patients. Selective reactivity to GD1a ganglioside was common when upper motor neuron signs were prominent. IgM reactivity to GM1 ganglioside was common in ALS patients with prominent lower motor neuron signs. Most patients with motor neuropathies had serum reactivity to both GM1 and GD1a gangliosides. These results provide further evidence of ongoing autoimmune processes in ALS patients. There is a strong relationship between serum antiganglioside antibodies and patterns of clinical involvement in ALS. PMID- 2913937 TI - Ilizarov orthopedic methods. Innovations from a Siberian surgeon. PMID- 2913938 TI - Arthroscopically assisted anterior cruciate ligament reconstruction. PMID- 2913939 TI - Pacemaker implant. Implications for perioperative nurses. PMID- 2913940 TI - Curriculum terms. Speaking the language. PMID- 2913941 TI - Proposed recommended practices. Laser safety in the operating room. Association of Operating Room Nurses. PMID- 2913942 TI - Using a survey to assess perioperative staff learning needs. AB - The learning needs survey is an effective means of ranking staff learning needs. The learning needs survey should be used every year to reevaluate the staff's needs and to incorporate new content areas. Newly hired nurses should take the survey only after they have been employed six months. The survey allows the educator to differentiate the needs of the new versus experienced staff, and it involves the staff in planning for their personal needs. The use of a learning needs survey keeps the content focused on the learner as opposed to the instructor's interest or needs. The staff rated needs differently than the instructor. For example, the staff rated a review of pediatrics growth and development low (13) even though there is an increased number of outpatient pediatric cases at our facility. Staff members' comments also provide data for follow-up and more specific surveys. A learning needs survey is the first step in providing continuing education for the perioperative staff. PMID- 2913943 TI - Thermal denaturation profiles of deoxypolynucleotide-ligand complexes: semiempirical studies. AB - We have semiempirically studied the thermal denaturation profiles of complexes formed between double strand polynucleotides and pure stabilizer nonspecific binding ligands. By using the McGhee model (J. D. McGhee, (1976) Biopolymers 15, 1345-1375) we have found a simple, analytical relationship between the melting temperature (Tm) and the Kh (intrinsic association constant), nh (apparent site size), and wh (cooperativity constant) values of the interaction. The validity of this approach strongly depends on the sigma value (sigma being the nucleation parameter of the DNA). Through the equation so obtained it is possible to calculate the Kh, nh, and wh values from the melting temperature of three experimental thermal denaturation profiles at different r (ligand/polynucleotide ratio) values. The method has been checked by studying the thermal denaturation profiles of daunomycin-poly(d(A-T)).poly(d(A-T)) complexes in two different salt concentrations. The results so obtained are compared with those previously described using other techniques. The applicability of the method here developed is discussed in relation with both the nature of the ligands and the value of the nucleation parameter (sigma). PMID- 2913944 TI - Partial purification of the acyl-CoA elongase of Allium porrum leaves. AB - Acyl-CoA elongase has been partially purified from leek (Allium porrum L.) epidermal cells. The microsomal elongase is first solubilized by Triton X-100. The solubilized proteins are then submitted to anion exchange chromatography on DEAE-cellulose and, finally, to gel filtration on Ultrogel 34 AcA. The purification of the elongase activity is accompanied by the enrichment in three major protein bands of 59, 61, and 65 kDa. The partially purified elongase is highly delipidated (about 10 mol lipid/mol of 60- to 65-kDa protein) and phosphatidylserine and phosphatidylethanolamine account respectively for 60 and 40% of the remaining phospholipids. The partially purified elongase retains some activities associated with fatty acid biosynthesis. The overall activity is strongly stimulated by the addition of exogenous lipids. In the presence of a mixture of PS, PE, and PC the C18-CoA elongase activity is increased more than sixfold. The Km value of stearoyl-CoA, in the presence of lipid vesicles, was determined to be 1.7 microM. PMID- 2913945 TI - The temporal relationships between P450E protein content, catalytic activity, and mRNA levels in the teleost Fundulus heteroclitus following treatment with beta naphthoflavone. AB - P450 induction occurs in some marine organisms following chemical exposure. The mode of 3-methylcholanthrene (MC)-type induction was evaluated by examining hepatic isozyme P450E content, catalytic activity, and mRNA levels in the marine teleost Fundulus heteroclitus after exposure to a single dose of beta naphthoflavone (BNF). P450E is the major teleost P450 induced by MC-type compounds and is the catalyst for aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD) activities. In a 20-day experiment, EROD activity was elevated in BNF-treated animals from Day 4 through Day 20. Increases in immunodetectable P450E showed the same trend as EROD activity, with consistently low control values and at least a 19-fold increase in the BNF treated fish. Precipitation of liver RNA in vitro translation products with anti P450E antibody gave no detectable signal from control fish, while the BNF-treated animals showed incorporation of [3H]leucine in a single 6,000 Mr band. In a shorter term experiment, EROD activity and P450E levels were again coordinately increased in response to BNF treatment, and immunoprecipitation of translation products from these fish showed a clear trend of increased P450E mRNA levels for all time points 6 h or more post-treatment. Hybridization of RNA from BNF-treated Fundulus with a trout P450IA1 cDNA also showed increases in a single band with time. The increases in P450E mRNA preceded increases in P450E protein and enzyme activity by about 25 h. However, P450E mRNA declined rapidly, reaching control levels by 5 days, while protein levels remained elevated for at least 13 days. The results support a hypothesis that transcriptional enhancement is involved in induction of MC-inducible P450s in fish, but indicate that P450E induction is also under other forms of regulatory control. PMID- 2913946 TI - Fluorescence energy transfer detects changes in fibronectin structure upon surface binding. AB - We report here the changes in intramolecular distances in human plasma fibronectin (Fn) detected, upon adsorption of the protein to the surface of the Cytodex dextran microcarrier, using a fluorescence energy transfer technique. The glutamine-3 residue, near the amino terminus of each chain, was labeled enzymatically with either monodansylcadaverine (dansyl) or monofluoresceinyl cadaverine (fluorescein) by use of coagulation factor XIIIa. Using this donor (dansyl)-acceptor (fluorescein) pair, and steady-state measurements, we demonstrated previously that the two amino termini of plasma fibronectin in solution were juxtaposed and separated by 23 A (C. Wolff and C.-S. Lai (1988) Biochemistry 27, 3483-3487). Upon adsorption to the microcarrier, the energy transfer was found to be completely abolished, suggesting that the surface binding induces a conformational change by which the distance between the two amino termini is increased to more than 70 A. Moreover, we have labeled the amino terminus of each chain with fluorescein and the two free sulfhydryl groups of each chain with coumarinyl-phenylmaleimide which serves as an energy donor. The emission spectra of the double-labeled protein in solution showed the occurrence of energy transfer, indicating that the relative distances between the amino termini and the free sulfhydryl group(s) are within 70 A. Upon surface binding, a decrease in the energy transfer between this donor-acceptor pair was also noted. The results presented here are consistent with the notion that plasma Fn undergoes a drastic conformational change upon surface binding, perhaps changing from a compact form to an extended form. This process may be important for the surface activation of the fibronectin molecule. PMID- 2913947 TI - Characterization of rat heart tropoelastin. AB - Several overlapping rat tropoelastin cDNA clones were isolated from a lambda gt11 rat heart cDNA library and their nucleotide sequence was determined. The corresponding deduced amino acid sequence of rat tropoelastin revealed strong homology to bovine and human tropoelastins although possessing some unique features including greater size (18%) and composition of repetitive units. Comparison of the amino acid sequence of rat tropoelastin to four other tropoelastin species reveals that the hydrophobic peptide repeat regions in the middle of each molecule and the crosslinking areas containing three lysine residues are remarkably conserved. A possible function for the clustering of three lysine residues in providing a mechanism for the in vivo reduction of dehydrolysinonorleucine via a redox shuttle with dihydrodesmosine is proposed. In addition, the COOH-terminal sequence of the rat tropoelastin is virtually identical to tropoelastins of other species in possessing a cysteine/arginine/lysine containing segment. There are no obvious amino acid insertions or substitutions in the COOH-terminal half of the rat tropoelastin molecule which would signal unique cleavage or glycosylation sites. Examination of the steady-state levels of rat tropoelastin mRNA in 8- and 12-day neonatal lung, heart, and aortic tissues showed that the amount of tropoelastin mRNA was abundant and of similar size (3.9 kb) in all three tissues. PMID- 2913948 TI - The de novo synthesis of molecular species of phosphatidylinositol from endogenously labeled CDP diacylglycerol in alveolar macrophage microsomes. AB - The de novo synthesis of molecular species of phosphatidylinositol (PI) from endogenously labeled CDP diacylglycerol (CDP-DG) and phosphatidic acid (PA), with [14C]-glycerol 3-phosphate, in microsomes of macrophages was studied using a recently developed HPLC technique. Endogenously labeled PA, CDP-DG, and PI were sequentially formed from labeled glycerol 3-phosphate through the addition of CoA, CTP, and then inositol into microsomes. The rate of formation of CDP-DG from endogenously labeled PA was low as compared with those of PA and PI. The low rate of CDP-DG synthesis suggests that it may be the rate-limiting step in the de novo synthesis of PI. Analysis of newly synthesized molecular species of PI by HPLC revealed that large proportions of radioactivity were associated with the 16:0 18:1, 16:0-18:2, 18:1-18:2, and 18:2-18:2 species, and a small amount, 2-3%, of radioactivity was associated with the 18:0-20:4 species. The profiles of newly synthesized PA and CDP-DG species were quite similar to those of PI species. This suggests that the enzymes involved in the formation of PI species from glycerol 3 phosphate show little specificity toward different molecular species of substrates. The results of the present study also suggest that free fatty acid composition in microsomes greatly affect the composition of the molecular species of PI synthesized through the de novo pathway, since the proportion of fatty acids utilized for the de novo synthesis of PI species was similar to that of free fatty acids in the microsomal membrane. PMID- 2913949 TI - Lipid peroxidation inhibitory factors in liver and muscle of rat, mouse, and chicken. AB - Glutathione- or sulfhydryl-dependent antioxidant factors that act to prevent lipid peroxidation have been reported in both microsomes and cytoplasm from rat liver. The cytoplasmic factor has been identified in several other tissues and species, but the distribution of the microsomal factor has not been reported. Chicken and mouse livers had much lower activities of the glutathione-dependent membrane-associated and cytoplasmic antioxidant factors than rat liver. Peroxidative damage to membranes has been hypothesized as a mechanism of tissue damage in muscular dystrophy. However, neither the chicken, mouse, nor rat had significant activities of the antioxidant factors in muscle. There was also no significant difference between normal and dystrophic chicken livers in the activity of the antioxidant factors associated with the microsomes or the cytoplasm, nor of the liver microsomal factor in normal and dystrophic mice. The results do not support an important role for the antioxidant factors in the pathogenesis of muscular dystrophy, and raise questions as to whether such factors are physiologically important in species other than rat or in tissues other than liver. PMID- 2913950 TI - Rat aglycotransferrin and human monoglycotransferrin: production and metabolic properties. AB - Rat transferrin (rTf), containing one complex glycan, and human transferrin (hTf), containing two complex glycans, were treated with peptide:N-glycosidase F (PNGase) under nondenaturing conditions. Apo rTf with a nonfucosylated standard biantennary glycan, but not its diferric counterpart, yielded satisfactory amounts (approximately 55% in 7 h) of aglyco Tf (AgTf). The presence of a chitobiose core fucose reduced yields to approximately 30%, whereas an additional NeuAc on the GlcNAc in the Man(alpha 1-3) branch had no adverse effect. Triton X 100 impaired deglycosylation. The main product (approximately 65%) obtained from apo hTf was monoglyco Tf (MgTf). Analysis of the cyanogen bromide fragments of MgTf revealed that PNGase did not discriminate between the two glycosylation sites of hTf. A negligible portion (2-4%) of AgTf, that was also obtained during the reaction, probably resulted from PNGase action on denatured hTf molecules. Modified Tfs were separated by affinity chromatography, radiolabeled, mixed with another preparation of interest, and injected in rats. Total-body radiation measurements showed that the half-life of rat AgTf was 19-20% shorter than that of rTf but 9% longer than that of asialo Tf. This suggests that close to 76% of the change in the degradative rate observed after desialylating rTf is referable to charge loss rather than the exposure of Gal residues. Human MgTf was catabolized by rats 8-9% faster than the parent protein, while human AgTf behaved in vivo like a denatured protein. It is concluded that sialyl carboxyls are a codeterminant of the normal lifetime of transferrins. PMID- 2913951 TI - Adsorptive endocytosis of lysosomal enzymes by human fibroblasts: presence of two different functional systems that deliver an acid hydrolase to lysosomes. AB - Endocytosis of human spleen beta-glucuronidase by human fibroblasts can be completely impaired by the competitive inhibitor mannose 6-phosphate or by pretreatment with acid phosphatase or endoglycosidases H or F. However, endocytosis of bovine spleen and liver beta-glucuronidase is partially impaired by the same treatments, suggesting that the bovine enzyme contains two endocytosis recognition markers located in separate enzyme domains. The mannose 6 phosphate recognition marker seems to be responsible for approximately 23% of the bovine enzyme endocytosis. The existence of two lysosomal endocytosis systems in human fibroblasts is supported by the following facts: (a) the rate of endocytosis of mannose 6-phosphate-containing human beta-glucuronidase was not affected by the presence of high levels of the bovine enzyme (which has only the other marker). (b) Anti-215K mannose 6-phosphate receptor antibodies selectively impair the endocytosis of the beta-glucuronidase containing mannose 6-phosphate. (c) Weak bases exert a differential effect on human and bovine endocytosis. beta Glucuronidase internalized by either system is targeted to secondary lysosomes of human beta-glucuronidase-deficient fibroblasts, where it is able to degrade accumulated glycosaminoglycans. These results suggest that human fibroblasts have two different and independent endocytic systems for targeting of acid hydrolases to lysosomes. PMID- 2913952 TI - Nitrogen metabolism in tumor bearing mice. AB - In experiments with whole animals infested with a highly malignant strain of Ehrlich ascites tumor cells, serial concentrations of amino acids were determined for host plasma, ascitic fluid, and tumor cells, throughout tumor development. Concentration gradients of glutamine, asparagine, valine, leucine, isoleucine, phenylalanine, tyrosine, histidine, tryptophan, arginine, serine, methionine, and taurine from the host plasma toward the ascitic liquid were established; while on the other hand, concentration gradients from the ascitic liquid toward the plasma were established for glutamate, aspartate, glycine, alanine, proline, and threonine. With the exception of aspartate the concentrations of these amino acids were highest inside the cells. Arginine was the only amino acid not detected in tumor cells. In vitro incubations of tumor cells in the presence of glutamine and/or glucose, as the energy and nitrogen sources, confirmed the amino acid fluxes previously deduced from the observed relative concentrations of amino acids in plasma, ascitic liquid, and tumor cells, suggesting that glutamate, alanine, aspartate, glycine, and serine can be produced by tumors. These findings support that changes in amino acid patterns occurring in the host system are related to tumor development. PMID- 2913953 TI - Coregulation of electron transport and Benson-Calvin cycle activity in isolated spinach chloroplasts: studies on glycerate 3-phosphate reduction. AB - Glycerate 3-phosphate-dependent O2 evolution was measured in intact chloroplasts in the absence of CO2. At all concentrations of added glycerate 3-phosphate oxygen evolution ceased before stoichiometric amounts of oxygen were evolved. The inhibition of glycerate 3-phosphate-dependent-O2 evolution increased with increasing concentrations of substrate added. A similar response was observed in chloroplasts treated with KCN which inhibits ribulose-1,5-bisphosphate carboxylase-oxygenase. Oxygen uptake via the oxygenase activity of this enzyme is therefore not the cause of the discrepancy in stoichiometry of oxygen release in this system. The addition of NaHCO3 to chloroplasts in which oxygen evolution was inhibited by glycerate 3-phosphate caused an immediate sustained rate of oxygen evolution in the absence of KCN but not with KCN present. Simultaneous measurements of chlorophyll a fluorescence showed that qQ remained oxidized, although net O2 evolution had ceased. As O2 evolution decreased, qE and delta pH increased. Upon the addition of the NaHCO3, QA became more oxidized while delta pH and qE were decreased, suggesting that the inhibition of electron transport at high glycerate 3-phosphate concentrations was mediated by photosynthetic control via delta pH. However, the levels of ATP, ADP, ribulose 1,5-bisphosphate, and Pi concentrations and ATP/ADP ratio. The stromal glycerate 3-phosphate content declined upon illumination until O2 evolution ceased. At this time a constant stromal glycerate 3-phosphate concentration of 8-10 mM was maintained while net import of glycerate 3-phosphate into the stroma had virtually ceased. The stromal triosephosphate content remained at a constant low level throughout but the glycerate 3-phosphate level increased slightly after addition of NaHCO3. The data provided by the measurements of thylakoid reactions and stromal metabolites suggest that photosynthetic electron transport is tightly coupled to the requirements of the stroma for ATP and NADPH. Glycerate 3-phosphate reduction requires much less ATP than the operation of the complete Benson-Calvin cycle since the stoichiometry of ATP and NADPH utilization is reduced to 1:1. We conclude that thylakoid electron flow is not sufficiently flexible to maintain NADPH and ATP production in the ratio of 1:1. This situation will favor overenergization of the thylakoid membrane, increased leakiness of protons, increased electron drainage to O2, and result in progressive inhibition of noncyclic electron flow. PMID- 2913954 TI - Immunological approach to the regulation of nitrate reductase in Monoraphidium braunii. AB - The effects of different culture conditions on nitrate reductase activity and nitrate reductase protein from Monoraphidium braunii have been studied, using two different immunological techniques, rocket immunoelectrophoresis and an enzyme linked immunosorbent assay, to determine nitrate reductase protein. The nitrogen sources ammonium and glutamine repressed nitrate reductase synthesis, while nitrite, alanine, and glutamate acted as derepressors. There was a four- to eightfold increase of nitrate reductase activity and a twofold increase of nitrate reductase protein under conditions of nitrogen starvation versus growth on nitrate. Nitrate reductase synthesis was repressed in darkness. However, when Monoraphidium was grown under heterotrophic conditions with glucose as the carbon and energy source, the synthesis of nitrate reductase was maintained. With ammonium or darkness, changes in nitrate reductase activity correlated fairly well with changes in nitrate reductase protein, indicating that in both cases loss of activity was due to repression and not to inactivation of the enzyme. Experiments using methionine sulfoximine, to inhibit ammonium assimilation, showed that ammonium per se and not a product of its metabolism was the corepressor of the enzyme. The appearance of nitrate reductase activity after transferring the cells to induction media was prevented by cycloheximide and by 6 methylpurine, although in this latter case the effect was observed only in cells preincubated with the inhibitor for 1 h before the induction period. PMID- 2913955 TI - Relationship of syphilis to drug use and prostitution--Connecticut and Philadelphia, Pennsylvania. PMID- 2913956 TI - Multistate outbreak of sporotrichosis in seedling handlers, 1988. PMID- 2913957 TI - The rash of roses. PMID- 2913958 TI - Effect of investigator bias on clinical trials. AB - Two clinical trials were performed to determine the relative efficacy of tioconazole, a new antifungal agent for treating patients with tinea pedis. One study compared the new agent with a placebo cream and the other with miconazole nitrate, an established effective antifungal agent. The investigators found a much higher "cure" rate for tioconazole when both treatment groups were known to receive active agents than the cure rate for tioconazole found in the placebo controlled study. These results showed that the expectations of investigators can influence their clinical evaluations. Such bias could also influence the results of clinical trials. PMID- 2913959 TI - Surgical correction of venous incompetence restores normal skin blood flow and abolishes skin hypoxia during exercise. AB - Posture has long been recognized to be a crucial factor in the etiology of venous leg ulcers. Activation of the stretch receptors in the veins by venous distention induces reflex vasoconstriction and hypoxia. In patients with defective venous return, exercise fails to reduce venous pressure when the legs are dependent; therefore, hypoxia persists during exercise. Surgical treatment of venous incompetence abolishes the abnormal venous reflux and restores the normal vasodilator response to exercise, thereby correcting the sustained hypoxia observed in patients with venous leg ulcers. PMID- 2913960 TI - Topical methotrexate therapy for psoriasis. AB - In vitro percutaneous penetration of methotrexate is enhanced with 1 dodecylazacycloheptan-2-one (laurocapram [Azone]). Laurocapram-containing methotrexate formulations provide effective local inhibition of epidermal DNA synthesis in the in vivo hairless mouse and minipig models, providing the biochemical rationale for topical use in the treatment of psoriasis. Topical methotrexate (0.1%, 0.5%, and 1%) in a laurocapram-containing formulation was tested in a two-center double-blind pilot clinical study of 42 patients with plaque psoriasis. Drugs were applied twice a day for six weeks, and lesions were scored weekly for erythema, scale, and elevation. An overall improvement of 50% or more in the combined scores for erythema, scale, and elevation was obtained with 0.1% methotrexate (64% of patients), 0.5% methotrexate (59%), and 1% methotrexate (56%) vs the vehicle alone (25%). These preliminary findings suggest that methotrexate preparations that provide adequate percutaneous absorption may have a beneficial effect in the treatment of psoriasis. PMID- 2913961 TI - Implications of dietary oils and polyunsaturated fatty acids in the management of cutaneous disorders. AB - A major proinflammatory metabolite of arachidonic acid, leukotriene B4, is known to accumulate in the lesions of psoriasis. Most of this metabolite is biosynthesized by the polymorphonuclear cells that infiltrate into the psoriatic lesions. Epidermal 15-lipoxygenase, on the other hand, metabolizes arachidonic acid into 15-hydroxyeicosatetraenoic acid (15-20:4n-6), presumably serving as a negative feedback to inhibit the local generation of leukotriene B4. Eicosapentaenoic acid, a major polyunsaturated fatty acid in fish oil, and gamma linolenic acid, a poly-unsaturated fatty acid in certain vegetable oils, are both metabolized by epidermal 15-lipoxygenase into 15-hydroxyeicosapentaenoic acid (15 OH-20:5n-3) and 15-hydroxyeicosatriaenoic acid (15-OH-20:3n-3), respectively. Both of these monohydroxy acids are potent in vitro inhibitors of leukotriene B4 generation. It seems reasonable, therefore, that adequate dietary supplementation with eicosapentaenoic acid or gamma-linolenic acid may offer a novel and nontoxic approach to suppressing cutaneous inflammatory disorders. PMID- 2913962 TI - Etretinate. Persistent serum levels after long-term therapy. AB - In 47 patients who received long-term etretinate therapy, we measured serum etretinate concentrations from one to 244 weeks after the discontinuation of therapy. The earliest posttreatment, nondetectable serum concentration of etretinate was observed at five weeks after treatment. Detectable serum concentrations (0.05 to 1.2 micrograms/dL) were observed more than two years (108, 111, 131, 136, and 150 weeks) following the discontinuation of therapy. Sequential serum concentrations obtained on eight individual patients were used to determine half-lives for this late-phase elimination. The median half-life for the 12 curves obtained was 12.5 weeks (range, 5.3 to 24.8 weeks). Since etretinate is stored in fat, we compared each patient's deviation from ideal body weight as a measure of excess body fat with various pharmacokinetic factors of etretinate elimination. Overweight patients tended to have slower elimination, maintain higher serum concentrations, and clear etretinate later. PMID- 2913963 TI - Reduced DNA repair in cultured melanocytes and nevus cells from a patient with xeroderma pigmentosum. AB - Patients with xeroderma pigmentosum (XP) have more than a 1000-fold increased risk of cutaneous melanoma. To determine if the XP DNA repair defect is present in cutaneous pigmentary cells, nevus cells and melanocytes from four large, pigmented nevi were cultured from a 12-year-old girl with XP. Cultured melanocytes showed dendritic morphologic features, contained mature melanosomes, and reacted with monoclonal antibody to tyrosinase. Nevus cells were spindle shaped and expressed nevus cell-associated antigens. Melanocytes, nevus cells, and dermal fibroblasts from the patient with XP all had a similar reduction in DNA repair: unscheduled DNA synthesis was 30% to 50% of that in normal fibroblasts following a 30 J/m2 ultraviolet dose. After a 6 J/m2 ultraviolet dose, the proliferative ability of XP nevus cells and fibroblasts was reduced to 10% of that of normal fibroblasts. This study indicates that cultured melanocytes and nevus cells express the characteristic XP DNA repair defect. PMID- 2913964 TI - Falsely elevated urinary level of vanillylmandelic acid induced by griseofulvin. AB - A 6-year-old girl with mild hepatitis was found to have an elevated urinary level of vanillylmandelic acid (VMA), but no cause for the elevation was found. The patient was receiving griseofulvin for treatment of tinea capitis, and this drug was suspected of causing a falsely elevated urinary VMA level. Four other patients receiving griseofulvin were also found to have elevated urinary VMA levels. In one patient, urinary VMA level determined by an alternate method was normal. PMID- 2913965 TI - Diffuse, ulcerating plaques and nodules. Necrobiotic xanthogranuloma (NXG) with paraproteinemia. PMID- 2913966 TI - Yellow papules on a middle-aged woman. Eruptive xanthomatosis (EX). PMID- 2913967 TI - Borrelia burgdorferi and localized scleroderma. PMID- 2913968 TI - Hyperpigmentation of the lower extremities associated with porphyria cutanea tarda. PMID- 2913969 TI - Elastic fibers in congenital melanocytic nevus. PMID- 2913970 TI - Cessation of illicit drug use in young adulthood. AB - The predictors of cessation of marijuana and cocaine use were examined in a longitudinal cohort of young adult men and women (N = 1222). Six domains of predictors were examined: socioeconomic background variables, participation in the social roles of adulthood, degree of drug involvement, social context of drug use, health status, and deviant activities and conventionality of life experiences. Factors that predicted cessation of use in adulthood paralleled those that predicted lack of initiation in adolescence: conventionality in social role performance, social context unfavorable to the use of drugs, and good health. A most important predictor was prior degree of involvement in licit and illicit drugs. In multivariate analyses, degree of prior drug involvement remained the strongest predictor of drug cessation for of marijuana use, while friends' use was the most important for cocaine. Those who use drugs in response to social influences are more likely to stop using them than those who also use drugs for psychological reasons. PMID- 2913971 TI - A comparison of male and female cocaine abusers. AB - Little has been written about the differences between male and female cocaine abusers. We therefore compared sociodemographic characteristics, reasons for cocaine use, drug effects, depressive symptoms, and psychiatric diagnoses in 95 men and 34 women hospitalized for cocaine abuse. Men were more likely to be employed, to hold higher status jobs, and to be self-supporting. Women were more likely to cite specific reasons for drug use, while men tended to use cocaine as part of a larger pattern of antisocial behavior. Women were diagnosed more often as having major depression, and their depressive symptoms improved much more slowly than men's when drug free. These findings suggest that women cocaine abusers may initially experience more residual problems, eg, depression and job dissatisfaction, than men after becoming drug free. Drug treatment centers should be alert to possible differences based on gender. PMID- 2913972 TI - Cortisol and sodium lactate-induced panic. AB - Sodium lactate infusions induce panic attacks in patients with panic disorder, but not in normal controls, by an unknown mechanism. We studied the plasma cortisol response to infusion of 0.5 mol/L of sodium lactate in 103 patients with panic disorder or agoraphobia with panic attacks, and 32 normal controls. Baseline cortisol levels did not distinguish early panickers from non-panickers and controls, but late panickers had significantly elevated baseline cortisol levels. In addition, a higher percentage of late panickers manifested an increase in cortisol during the baseline period compared with the other groups. Despite the fact that late panickers manifested elevated baseline cortisol levels, early panickers had significantly greater somatic distress as measured by the Acute Panic inventory. There was no increase in cortisol with lactate-induced panic, and cortisol levels fell significantly during the lactate infusion in all groups. Cortisol elevation occurred with moderate anxiety but not with severe panic anxiety. These results suggest different pathophysiologic mechanisms of early and late panic, and differences between anticipatory anxiety and panic anxiety. PMID- 2913973 TI - Lactate and hyperventilation substantially attenuate vagal tone in normal volunteers. A possible mechanism of panic provocation? AB - Many aspects of panic attacks, eg, palpitations, tremor, sweating, and an emotional sense of "fear," have been theorized to arise from sympathetic nervous system activation. However, most studies have not demonstrated clearly increased levels of catecholamines during an attack, which is contrary to this hypothesis. To explore another possible cause for the physiological changes known to occur during a panic attack, we assessed parasympathetic nervous system activity by measuring vagal tone during treatments known to produce panic symptoms: sodium lactate administration and hyperventilation. Our findings showed a marked reduction in vagal tone during both procedures. We postulate that withdrawal of parasympathetic activity may explain some of the physiological changes occurring in panic attacks and be contributing to the origin of panic. PMID- 2913974 TI - Electroencephalographic sleep in panic disorder. A focus on sleep-related panic attacks. AB - Sleep electroencephalograms were studied in 13 patients with panic disorder, six of whom experienced panic from sleep, and seven controls. Sleep was disturbed in the patients, as manifested by increased sleep latency, decreased sleep time, and decreased sleep efficiency. Rapid eye movement (REM) latencies were not reduced in the patient group. All six of the panic awakenings were preceded by non-REM sleep, which could be further characterized as a transition from stage II toward delta sleep. The overall degree of sleep disturbance (ie, sleep latency, sleep efficiency) did not appear to be influenced by the occurrence of sleep panic. There was also an association of increased REM latency with nights of sleep panic. PMID- 2913975 TI - Who can say no to illicit drug use? Response to a new study. PMID- 2913976 TI - Light therapy and the seasonal affective disorder. PMID- 2913977 TI - Prevention of thromboembolism in hip-fracture patients. Comparison of low-dose heparin and low-molecular-weight heparin combined with dihydroergotamine. AB - In a prospective, double-blind, controlled study, we compared the antithrombotic efficacy of low-dose heparin with dihydroergotamine (A), low-molecular-weight heparin with dihydroergotamine (B), and placebo (C). Two hundred and thirteen patients surgically treated for fractures of the hip were randomly divided into three groups. One hundred and sixty-one patients were analyzed. All thrombi were verified by ascending phlebography. Nine patients died within 1 month after operation. A and B proved to be equally safe but failed to provide any protection against deep-vein thrombosis, although B showed a tendency to reduce the incidence. Mortality within 1 month of operation was unaffected by the type of prophylaxis. PMID- 2913978 TI - The influence of mediolateral deformity, tibial torsion, and foot position on femorotibial load. Prediction of a musculoskeletal computer model. AB - The influence of mediolateral deformity, tibial torsion, and different centers of foot support was studied with a three-dimensional computer model that incorporates the significant muscles of the lower extremities needed for quasi static walking. This theoretical method avoids the variability in gait pattern from the pain and discomfort associated with deformity in patients. The study illustrates the possible importance of the muscle force on the load across the knee and ankle. High strains in the medial gastrocnemius and the medial hamstring created particularly high loads in the medial compartment of the knee. Internal torsion and varus deformity were associated with the highest loads in the medial compartment of the knee, although the peak load for each deformity occurred in different phases of the gait cycle. Both external torsion and valgus deformity generally decreased the load in the medial compartment, but early in the gait cycle external torsion increased the loads on the medial side. In addition, when the center of support of the body was in the forefoot, the loads through the knee were lower than when foot support was at the heel. As expected, if the center of support was on the lateral foot line, the lateral compartment was subjected to more load and, conversely, when the center of support was on the medial part of the foot the medial compartment of the knee was more loaded. Although the predicted forces agree well with those found with other methods, we think that the model is best used to measure the direction of influence of specific factors. PMID- 2913979 TI - Advantages of diagnosing bacterial spondylitis with magnetic resonance imaging. AB - We report on 16 cases of suspected spondylitis in which we used magnetic resonance (MR) imaging to confirm or exclude the diagnosis. MR has several advantages, one of which is to permit diagnosis of this disease in the early stages without major risks. In addition, MR permits recognition of complications such as paravertebral or intraspinal abscess formation with a high security and accuracy. Moreover, it is possible to show spondylitic alterations in three different planes. To differentiate this disease from metastatic or tumorous lesions the technique with T1- and T2-weighted images is helpful. As a result, MR imaging can shorten the time between onset and diagnosis of spondylitis. PMID- 2913980 TI - Trochanteric fractures--a clinical and radiologic evaluation of McLaughlin, Ender, and Richard's osteosynthesis. AB - Four hundred and thirty femoral trochanteric fractures operated with nail-plate (McLaughlin), Ender, or sliding screw-plate (Richard) osteosynthesis were followed up radiographically and clinically. For each method of osteosynthesis the initial nail position was correlated to the occurrence of late mechanical complications. Unstable fractures were associated with a higher incidence of one or more clinical complications such as repeated surgery, post-operative death, or increased pain. For Ender osteosynthesis correlations were found between several mechanical and clinical complications, while for Richard's osteosynthesis mechanical complications were significantly correlated to repeated surgery only. McLaughlin and Ender osteosyntheses had a higher incidence of reoperations than Richard's osteosynthesis, whereas the mobility and ADL function were the same at 4 months. PMID- 2913981 TI - Magnetic resonance imaging of tibial shaft fracture repair. AB - Magnetic resonance imaging (MRI) of normal fracture repair was evaluated in six randomly chosen adult patients with solitary, closed fractures of the tibial shaft by obtaining serial MRI scans until union of the fracture. The mean time to union was 14.3 weeks. Ultralow-field 0.02-Tesla magnet equipment was used. The MRI scans showed a characteristic pattern of events common for all the patients studied and compatible with the recognized histomorphology of fracture repair. The intramedullary cavity demonstrated a marked decrease in the signal intensity. In the soft tissues surrounding the fracture the initially evenly high signal intensity gradually developed a granular appearance with embedded low-intensity nodules. These nodules corresponded to the first areas to become mineralized, as could be seen on plain radiographs several weeks later. The question of whether MRI renders it possible to predict delayed union calls for continued investigations. PMID- 2913982 TI - Experimental photoablation of meniscus cartilage by excimer laser energy. A new aspect in meniscus surgery. AB - Excimer lasers have been demonstrated to provide a very precise and circumscribed ablation of synthetic polymers and biological tissues. We investigated in vitro the use of ultrashort pulsed ultraviolet excimer-laser energy for controlled removal of meniscus cartilage under the aspects of arthroscopic meniscectomy. A krypton-fluorine gas mixture was used to achieve laser emission of 248-nm wavelength. A total of 22 human menisci obtained either by operation or necropsy were irradiated over a range of energy fluence (2.15-3.07 J/cm2/pulse), repetition rates (5-20 Hz), and exposure time (15-60s). Ablation rates of 4.00 5.76 microns per pulse were obtained. Light-microscopic examinations demonstrated tissue ablation without any evidence of pathological changes associated with continuous-wave laser irradiation. Effects of laser energy were clearly limited to the target of the laser beam, and tissue removal proceeded without production of heat or smoke. Due to the lack of pathological alterations observed, excimer laser irradiation of meniscus cartilage may prove to be advantageous for precisely cutting and removing menisci without injury to the surrounding normal tissue. Clinical application of excimer-laser irradiation includes the development of suitable fiberoptics and laser coupling, as well as modification of fiber tips. PMID- 2913983 TI - Torsional characteristics of the Minns meniscal knee prosthesis. AB - A quasi-static analysis of axial rotation of the femoral component and the torsional forces at different angles of knee flexion was performed on knee preparations. The meniscal knee design had very much lower axial torque against axial rotation characteristics through the whole range of knee flexion than the total condylar design and could be rotated up to 59 degrees in both internal and external rotation before dislocating (i.e., a total axial rotation of 118 degrees). The sliding plateau design had torque-rotation characteristics comparable to those of the total condylar design. Torsional strain was measured on cemented and uncemented preparations, and little difference between the two was observed. PMID- 2913984 TI - Haematogenous osteomyelitis of the first metatarsal sesamoid. A case report and review of the literature. AB - A rare case of haematogenous osteomyelitis of the sesamoid of the first metatarsophalangeal-joint visualized by a CT-scan have been presented. The characteristics of this disease have been stressed. When the diagnosis had been considered treatment should be surgical drainage with debridement of all infected tissues. Previous authors recommend antibiotic treatment, but it was not given to this patient. There was total cure after three months. PMID- 2913985 TI - Traumatic anterior dislocation of the hip. AB - A discussion is presented of traumatic anterior dislocation of the hip joint on the basis of three representative case reports. One patient had an iliac or pubic dislocation, the other two were obturator dislocations, including one with an associated femoral head fracture. All three patients were treated without surgery. After an average follow-up time of twenty-seven months, the results were excellent. Therapeutic guide-lines and recommendations are given for this infrequent type of injury. PMID- 2913986 TI - Impalement injuries. AB - Impalement injuries are still seen today and constitute a challenging form of trauma. Our experience with four cases is presented. The management of each case has to be individualised. It may not be necessary to lay open the tract taken by the impaling object in every case. PMID- 2913987 TI - Dislocation of the shoulder with ipsilateral humeral shaft fracture. AB - A case of dislocation of the shoulder and ipsilateral fracture of the shaft of the humerus is reported. The mechanism of this injury is detailed. The use of the limb lengthening apparatus as an external fixator, which rendered the management of this combination injury easy, is described. The literature on this subject is reviewed. PMID- 2913988 TI - Neurotrauma in country hospitals: the role of computerized tomography scanning. PMID- 2913989 TI - Cervical spine injuries in road traffic crashes in South Australia, 1981-86. AB - The records of all cases of injury to the cervical spine sustained in road crashes for the 6 year period (1 January 1981 to 31 December 1986) which were admitted to the Spinal Injuries Unit of the Royal Adelaide Hospital, to the Adelaide Children's Hospital, or were identified at post-mortem examination were examined, and the relevant data extracted. There were 291 cases in the non-fatal group, and 161 in the fatal group. These represent a complete enumeration of all such patients in the state of South Australia over the 6 year period, given that up to 50% of cervical injuries in fatal cases can be missed. Comparison of the two groups showed that the fatal group had a much higher proportion of pedestrians, and persons over 50 years of age. About one-half of the fatal group had injuries at the level of C1 or the atlanto-occipital articulation. The most frequent level of injury in the non-fatal group was C2 (29.2%). About 30% of the non-fatal cases had some spinal cord damage. Case fatality rates were calculated, and ranged from 100% for injury at the atlanto-occipital articulation to 8% at C2. The fatality rate of pedestrians was about 4 times higher than that of vehicle occupants. About three-quarters of all cervical spine injuries occurred in vehicle occupants. There was an increase in the number of cases occurring in each year of the period studied. This rise was noted in non-fatal cases, in males, in vehicle occupants, and in crashes in the country. PMID- 2913990 TI - Cervical spine injuries in road traffic crashes. PMID- 2913991 TI - How useful is pre-operative computerized tomography scanning in staging rectal cancer? AB - This study evaluates prospectively the reliability of computerized tomography (CT) in the pre-operative staging of 80 patients with rectal cancer. The scans were performed and reviewed by one radiologist without knowledge of either the operative findings or the final clinicopathological stage of the tumours. Fourteen of 60 patients (23%) who had a potentially curative resection were correctly staged by CT. The tumour was understaged in 28 patients (47%) and was overstaged in 18 patients (30%). CT did not identify the one patient with histological demonstration of invasion of an adjacent organ was equivocal or incorrect in 10 others on the question of adjacent organ invasion. CT failed to define accurately local tumour spread confined to the rectal was (positive predictive value (PPV) 23%), identify venous invasion (PPV 35%) or involved regional lymph nodes (PPV 42%). However, the negative predictive value for excluding synchronous liver metastases was 90%, and 11 patients who subsequently developed histologically confirmed local recurrence were all correctly diagnosed on CT. These findings suggest that pre-operative examination of patients with rectal cancer by CT is not routinely justified specifically for purposes of staging the disease. PMID- 2913992 TI - Predicting survival in bilateral breast carcinoma. AB - Survival in 38 patients with bilateral breast cancer has been studied. The tumours were synchronous in 14 patients and metachronous in 24. Survival was less than that predicted for either tumour on the basis of a previously developed index involving lymph node status, oestrogen receptor content, progesterone receptor content, and patient age. Simple addition of the indices for the two tumours gave better predictor although this also overstated the prospects for survival for both synchronous and metachronous tumours. This experience suggests, therefore, that the prospects for survival for patients with suggests, therefore, that the prospects of survival for patients with synchronous or metachronous bilateral breast carcinoma is poor, and worse than might reasonably be anticipated. PMID- 2913993 TI - Cancer of the tongue and oral cavity in Auckland, New Zealand, 1970-86. AB - This report comprises a retrospective review of the clinical data on 157 patients seen in the Auckland area having a diagnosis of cancer of the tongue, floor of the mouth, inferior alveolus, or buccal mucosa (retromolar area, vestibule of the mouth, and cheek mucosa) during 1970-86. One hundred patients were male, 95% were European, 85% were cigarette smokers, and 58% had a history of high alcohol intake. All primary tumours were squamous cell carcinomas, 50% were located in the tongue, 27% in the floor of the mouth, and 11.5% each in the buccal mucosa and inferior alveolus. The majority (60%) of patients with tongue cancer were clinically stage I at presentation while other intra-oral tumours were evenly distributed between stages I and IV. Surgical resection of the primary intra-oral lesion produced local control in 90% of stage I tumours, but this fell to below 70% in stage II-IV tumours. Most patients (82%) who recurred locally had positive or 'close' margins, and this rate of local tumour recurrence as a consequence of narrow margins did not decrease with the addition of adjuvant radiotherapy. Of those patients with stage I disease who received only treatment of the primary lesion, 20% later developed regional nodal disease which was controlled in more than half by neck dissection, but control was achieved only in 11% of patients treated with radiation. The presence of regional disease at presentation was associated with a poor prognosis. It is concluded that local control of inferior oral cavity tumours can be achieved if resection is accomplished with clear margins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2913994 TI - Fine needle aspiration in the diagnosis of salivary gland lesions. AB - Fine needle aspiration biopsy (FNAB) of salivary glands was performed in 187 patients. In 106 patients with satisfactory FNAB smears who proceeded to surgery, the original cytologic diagnosis was compared with subsequent histopathology. There were 74 benign tumours and 25 malignant tumours. Nineteen of the latter were primary malignant neoplasms of the salivary glands, and 6 were metastatic. The cytologic diagnosis by FNAB correlated exactly with the histologic diagnosis in 95% of benign neoplasms and in 68% of malignant neoplasms, with an overall accuracy of 88%. A false negative diagnosis for malignancy was made in five cases and a false positive diagnosis in one case. Hence the sensitivity for malignancy was 80% and the specificity was 99%. The most frequently misdiagnosed lesions were pleomorphic adenoma and muco-epidermoid carcinoma. FNAB of salivary gland lesions is easy to perform and free of complications, but the cytologic patterns may be difficult to interpret, and considerable experience is necessary in order to achieve a high diagnostic accuracy. PMID- 2913995 TI - Colostomy closure. AB - One hundred and forty-seven colostomies were closed in 146 patients at Wellington Hospital between 1 January 1978 and 1 January 1987. The majority of stomata were formed in patients with colorectal cancer. At least one additional significant procedure was undertaken at the time of stoma closure in 10 patients. The overall complication rate was highest in those patients undergoing closure of a sigmoid end-colostomy (50%). Three complications resulted in death (2%). Twenty-four patients (16.3%) developed wound infections. Five patients developed 'leaks' (3.4%). The use of prophylactic antibiotics appeared to reduce the rate of infection significantly. The highest rates of wound infection and leakage occurred in patients in whom drains were used. Wound infections increased hospital stay. Thirty-one non-bowel or wound-related complications occurred in 25 patients. PMID- 2913996 TI - D-dimer levels in blood salvage for autotransfusion. AB - Autotransfusion of operatively salvaged blood is an increasingly attractive and used practice. The fear of precipitating a coagulopathy, however, has retarded the acceptance of autotransfusions and the efficiency and convenience of banked homologous blood has proved too competitive in recent years. The risk of transmitting diseases with bank homologous blood has seen a resurgence in the development of autotransfusion. The current alternatives to pre-operative autologous banking or dilution are the reinfusing of filtered salvaged blood, and of blood which has been further processed by washing which involves the extra cost of time, personnel and equipment. Washing removes possible harmful products, but also removes coagulation factors. D-Dimer levels were estimated by monoclonal antibody techniques in salvaged blood before and after washing in 10 patients undergoing aortic surgery and in 10 u of homologous banked blood. The D-Dimer levels in the unwashed blood were increased 85 times, but were normal in the washed blood. D-Dimers are an indication of activation of the coagulation and fibrinolytic systems and the presence of fibrin degradation products. PMID- 2913997 TI - Spinal arachnoiditis following subarachnoid haemorrhage. AB - Two cases of chronic adhesive spinal arachnoiditis following documented subarachnoid haemorrhage (SAH) are reported. Both cases progressed to severe spinal cord dysfunction with paraplegia. It is hoped that this case report will highlight this uncommon but extremely disabling complication of SAH. PMID- 2913998 TI - Hydrofluoric acid burns of the hands: a case report and suggested management. AB - Hydrofluoric acid is a strong inorganic acid. It is used commercially in a number of industrial settings. Injuries sustained from this acid are infrequent and the management of such cases is therefore not well known. Tissue destruction caused by this acid is rapid and severely painful and may result in disfigurement if treatment is not instituted promptly. Methods of management of hydrofluoric acid burns are still controversial and no single type of therapy has yet been determined. The patient was managed according to the guideline in the literature, but, in the presence of severe digital oedema, intra-arterial infusion of gluconate was performed. This resulted in rapid relief of pain and prevention of continuing tissue destruction. PMID- 2913999 TI - Kienbock's disease in an 8 year old boy. AB - Kienbock's disease is an uncommon condition occurring in adults but rarely in children. A case occurring in an 8 year old boy is presented. This patient showed a strongly negative ulnar variant, which may have been an aetiological factor in his young presentation. PMID- 2914000 TI - One-session treatment for specific phobias. AB - A rapid and effective treatment for specific phobias, in which the treatment is done in one single session, is described in detail. The treatment method consists of a combination of exposure in vivo and modeling. The short- and long-term outcome for a consecutive series of 20 patients are reported. Mean treatment time was 2.1 h and at follow-up after an average of 4 yr 90% were much improved or completely recovered. PMID- 2914001 TI - Fears in children and adolescents: reliability and generalizability across gender, age and nationality. AB - In this study, the reliability and generalizability of the FSSC-R was explored across gender, age and nationality. 594 normal children and adolescents from the United States and 591 normal youths from Australia participated. Results confirmed that the schedule is internally consistent across these subject parameters, and that the factor structure is fairly robust. Future directions, including use of the schedule with client populations, are addressed. PMID- 2914002 TI - Children's strategies for coping with depression. AB - Rippere (1974-1983) has investigated adults' commonsense beliefs concerning behavioural strategies for coping with depression. The study report here was concerned with the developmental aspects of the concept of 'common knowledge'. It was designed in order to investigate, through conversations with children of various ages, the hypothesis that children may possess a common knowledge concerning the 'things to do' when they are feeling depressed. 120 children distributed across seven age groups (ranging from 4-11 yr) were asked in an open ended interview "What's the thing to do when you're feeling depressed?". Their responses were subjected to frequency counts and content analysis. Content analysis of the data indicated that 50% of all responses mentioned 'Play' strategies, 12% mentioned 'Help and comfort seeking', and 11% mentioned 'avoidance' activities. There was an inverse relationship between the frequency with which items were mentioned and the number of items mentioned at that frequency. This finding supports the notion of the existence of a canon of commonsense 'things to do' when feeling unhappy, and accords well with the findings of Rippere. PMID- 2914003 TI - The effects of post-stress exposure to alcohol upon the development of alcohol consumption in rats. AB - A preference-drinking situation was used to test the effects of conditioned inhibition training upon relative alcohol preference. Using a backward, conditioned inhibition paradigm, water-deprived rats received daily shock presentations, followed immediately by alcohol exposure in a different neutral chamber. This post-shock exposure to alcohol drinking cues increased daily alcohol intake in the home cage, as tested 5 h later, relative to a no-shock control group. Results were interpreted in terms of a conditioned antagonistic response interpretation of conditioned inhibition--increased relative preference for alcohol cues developed as a result of the association of alcohol cues with a post-shock, relief/relaxation response. These results have implications for the role of conditioned inhibitory processes in the initial development of alcoholism. PMID- 2914004 TI - A longitudinal study of the intrusiveness of cognitions in test anxiety. AB - Medical students who had to undergo an important set of examinations were asked to fill out two questionnaires, the first early in the term, the second 1 or 2 wk before the exams. Students whose anxiety increased substantially between the two questionnaire administrations reported that their thoughts had become more intrusive on a number of parameters including distress, frequency and dismissability. Subjects whose anxiety increased only moderately or not at all reported correspondingly smaller changes in intrusiveness. There was considerable stability in reported cognitions over time, but changes in anxiety were related to changes in reports of thought content. The perceived probability of negative outcomes did not vary over time. These results indicate that changes in anxiety levels over time are related to several parameters of intrusiveness as well as thought content. PMID- 2914005 TI - Dental phobias and anxieties: evidence for conditioning processes in the acquisition and modulation of a learned fear. AB - The present study investigated some of the factors which differentiate individuals with dental anxieties and phobias from those without such fears. In particular, two questions were addressed: (i) What differentiates subjects who have never been anxious about dental treatment from subjects who at some time have been anxious? and (ii) What factors lead to subjects changing their attitudes either from anxious to relaxed or from relaxed to anxious? The results suggest that the factors which influence the acquisition and modulation of dental anxieties are consistent with the associative and representational processes portrayed in contemporary models of human conditioning. Subjects who reported never having had anxieties about dental treatment were less likely to have had a painful dental treatment than subjects who did report an anxiety. Subjects who did report a painful dental experience but did not acquire anxiety reported a history of dental treatment favourable to the operation of latent inhibition. Subjects who reported that they were good at enduring pain were more likely to report a longer interval between their very first dental treatment and their first painful dental treatment. Under some conditions in which latent inhibition should have precluded the acquisition of a dental fear, an anxiety appeared to be acquired because a very painful experience had attenuated the latent inhibition process. Subjects whose dental anxiety did not remit reported significantly more painful and traumatic dental experiences than subjects whose anxiety did remit. PMID- 2914006 TI - Leisure interest patterns and subjective stress in college students. AB - A first study of the Leisure Interests Checklist (LIC) is reported based on a large (N = 670) normative sample of college students. Acceptable reliability was found on the total interest scores, and on both rationally- and factorially derived LIC subscales. The BAROMAS stress scales were also studied concurrently with the same college students, and normative data are provided from that sample. Interest in very active diversions and Sports on the LIC did correlate with confidence in doing sports on the BAROMAS. Otherwise, the two instruments showed little overlap. Comparisons between ethnic and gender groupings mainly agreed with advance expectations by disclosing culturally conventional differences in response patterns. The LIC appears promising for future use in both applied and research contexts. PMID- 2914007 TI - Memory deficits in compulsive checkers: replication and extension in a clinical sample. AB - Thirteen checkers and twelve noncheckers, identified on the basis of their responses to the checking subscale of the Maudsley Obsessional-Compulsive Inventory (MOCI; Rachman and Hodgson, 1980), were recruited from a sample of 99 consecutive admissions to the outpatient department of a community mental health center. Consistent with our previous research with nonclinical samples of college students (Sher et al., 1983, 1984), checkers were found to show deficits in memory, especially recall for recently completed actions, compared to noncheckers. This result demonstrates the replicability of our previous findings across different types of samples and implicates deficits in memory for actions as a potentially important determinant of checking behavior. Assessment of spontaneous imagery associated with the anamnestic process suggested that checkers utilized less imagery, especially visual imagery, when recalling biographical information. Additional measures collected at the time of testing indicated that checkers were more neurotic and reported more psychological distress than noncheckers. PMID- 2914008 TI - A controlled comparative investigation of psychological treatments for chronic sleep-onset insomnia. AB - A sample of physician-referred chronic insomniacs was randomly allocated to either progressive relaxation, stimulus control, paradoxical intention, placebo or no treatment conditions. Treatment process and outcome were investigated in terms of mean and standard deviation (night to night variability) measures of sleep pattern and sleep quality. Only active treatments were associated with significant improvement, but the nature of treatment gains varied. In particular, stimulus control improved sleep pattern, whereas relaxation affected perception of sleep quality. All improvements were maintained at 17 month follow-up. Results are discussed with reference to previous research and guidelines are given for clinical practice. PMID- 2914009 TI - The incubation theory of fear/anxiety: experimental investigation in a human laboratory model of Pavlovian conditioning. AB - The aim of this work was to test Eysenck's incubation theory of fear/anxiety in human Pavlovian B conditioning of heart rate (HR) responses. The conditioned stimuli (CSs) were phobia-relevant slides (snakes and spiders) and the unconditioned stimuli (UCSs) were aversive noises. The subjects were presented with two levels of noise intensity during acquisition and three levels of nonreinforced CS presentation (CS-only) in a delay differential (CS+/CS-) conditioning paradigm (2 x 3 x 2). Consistent with the incubation theory, conditioned HR acceleratory responses were sustained (resistance to extinction) for high-noise intensity and short-presentations of CS-only subjects. During the extinction phase, HR acceleratory responses quickly extinguished in low-noise intensity groups after the first presentations of CS-only. These findings were interpreted as support for the incubation theory of phobic fear. PMID- 2914010 TI - Interspecies homology of liver microsomal cytochrome P-450. A form of dog cytochrome P-450 (P-450-D1) crossreactive with antibodies to rat P-450-male. AB - P-450-male is a male specific form of cytochrome P-450 in rat liver microsomes. Cytochrome P-450 crossreactive with anti-P-450-male antibodies was purified to an electrophoretical homogeneity from liver microsomes of male beagle dogs. The specific content of the purified cytochrome P-450 (P-450-D1) was 16.9 nmol/mg protein. The apparent monomeric molecular weight of P-450-D1 was 48,000, which was smaller than P-450-male (51,000). P-450-D1 showed similarities in spectral properties, N-terminal amino acid sequence, and catalytic activities with some limited exceptions: P-450-D1 did not catalyze 2 alpha-hydroxylation of testosterone and progesterone and catalyzed 21-hydroxylation of progesterone. Based on these results, we propose that P-450-D1 is a form of cytochrome P-450 in the same gene subfamily as P-450-male. PMID- 2914011 TI - Covalent binding of 4,4'-methylenebis-(2-chloroaniline) to rat liver DNA in vivo and of its N-hydroxylated derivative to DNA in vitro. AB - The binding of [ring-3H]4,4'-methylenebis(2-chloroaniline) (MOCA) to rat liver DNA following i.p. injection is demonstrated. Three discrete adducts were eluted on HPLC following enzymic hydrolysis to the nucleoside level. Three adducts, with the same retention times on HPLC, were present after i.p. injection of the N acetyl derivative of MOCA tritiated in the benzene rings. Only two of these adducts were found when the N-acetyl derivative, tritiated on the acetyl group, was used. Thus, at least one of the adducts formed by MOCA is not acetylated. The N-hydroxy derivative of MOCA was synthesised and reacted with DNA in vitro. Following enzymic hydrolysis of this DNA, the major product was shown to co-elute with the radiolabelled non-acetylated adduct produced in the liver DNA of animals injected with [ring-3H]MOCA. This same compound was also isolated following the reaction of N-hydroxy-4-amino-3-chlorobenzyl alcohol with DNA, and subsequent enzymic hydrolysis. The NMR and mass spectra of the synthetic adduct were consistent with N-(deoxyadenosin-8-yl)-4-amino-3-chlorobenzyl alcohol. Thus, the major adduct formed in vivo has involved cleavage of the bond between the methylene bridge and one of the aromatic nuclei of MOCA. PMID- 2914012 TI - Effect of glucose and gluconeogenic substrates on fasting-induced suppression of acetaminophen glucuronidation in the rat. AB - Previous studies in rats have shown that an acute fast decreases the apparent rate constant for glucuronidation of hepatotoxic doses of acetaminophen which results in a prolongation of the mean residence time of the drug in the animals and, hence, increased acetaminophen reactive metabolite formation and liver injury. Since acetaminophen glucuronidation under these conditions is limited by UDPGA formation, we have attempted to reverse the potentiating effects of fasting by administering glucose or gluconeogenic substrates. Histological and pharmacokinetic studies revealed that glucose (2 g/kg, i.p.) given 0.25 and 1.5 hr after acetaminophen (700 mg/kg, i.p.) did not protect the rats from liver injury or enhance acetaminophen glucuronidation. The administered glucose did not increase hepatic levels of UDP-glucose or UDPGA either basally or following administration of a hepatotoxic dose of acetaminophen. Administration of the gluconeogenic substrates, lactate, alanine, fructose and galactose, raised blood glucose levels, but did not protect the rats from liver injury or enhance glucuronidation, suggesting that the glucose-6-phosphate formed from these compounds was not available for UDPGA production for acetaminophen glucuronidation. Collectively, these studies indicate that administration of glucose and these gluconeogenic substrates does not reverse the fasting-induced potentiation of acetaminophen hepatotoxicity, and that the rate-determining step for UDPGA synthesis for glucuronidation of hepatotoxic doses of acetaminophen is prior to UDP-glucose formation. PMID- 2914013 TI - Glutathione conjugation and induction of a 32,000 dalton stress protein. AB - Chinese hamster ovary cells were exposed to various concentrations of diethylmaleate in order to produce various levels of intracellular glutathione (GSH) depletion. Exposure to a 20 microM concentration or more of diethylmaleate depleted the intracellular glutathione concentration by 80% or more and resulted in enhanced synthesis of two 32 kDa proteins which exhibited a pI of about 6.5. Exposure of cells to 50 microM buthionine sulfoximine for 24 hr reduced GSH levels by 95% but did not enhance the synthesis of this protein. Addition of diethylmaleate to buthionine sulfoximine-treated cells resulted in enhanced synthesis of the 32 kDa protein however. Exposure to 0.4 mM diamide triggered the synthesis of several heat shock proteins but did not induce the synthesis of the 32 kDa protein. These results indicated that enhanced synthesis of the 32 kDa protein occurred only after glutathione depletion exceeded 80% and required formation of a glutathione conjugate. PMID- 2914014 TI - Membrane potential differences between adriamycin-sensitive and -resistant cells as measured by flow cytometry. AB - Using the fluorescent membrane potential probe, 3,3'-dihexyl-oxacarbocyanine (DiOC6(3], we found a 4-fold higher uptake in Adriamycin (ADM)-sensitive versus resistant Friend leukemia cells (FLC). When sensitive cells were treated in the presence of high potassium (120 mM K+), there was a greater than 80% reduction of DiOC6(3) uptake. Using carbonylcyanide 4-trifluoromethoxy-phenylhydrazone (FCCP), a specific inhibitor of mitochondrial membrane potential, DiOC6(3) accumulation was reduced by less than 30% in these cells. Both results support the conclusion that a greater uptake of DiOC6(3) in ADM-sensitive than in -resistant cells indicates an increased plasma transmembrane potential. Since electronegative plasma membrane potentials are a driving force for the transport of lipophilic positively-charged compounds, differences in membrane potentials between sensitive and multiple drug resistant (MDR) tumor cells could have an important influence on drug accumulation and cytotoxicity. The drugs which our ADM resistant FLC display multiple drug resistance to are positively charged. In MDR FLC, the calcium channel antagonist, verapamil, has been shown to block the efflux of Rhodamine 123 (Rho 123) and other positively-charged compounds. Since DiOC6(3) is also positively-charged, we used verapamil to investigate its effects on drug uptake. In MDR FLC, verapamil increased DiOC6(3) accumulation by 1.9 fold, whereas in sensitive cells it was increased 1.5-fold. In contrast, verapamil increased the levels of Rho 123 in resistant cells 7.8-fold but lowered them in sensitive cells 1.5-fold. The minimal loss of DiOC6(3) from both sensitive and MDR cells and the above results can best be interpreted as indicating that DiOC6(3) is not transported by the efflux "pump" system but that verapamil induces a plasma membrane potential increase in sensitive and resistant cells that DiOC6(3) is sensitive to. On the other hand, since Rho 123 did appear to be actively effluxed from these resistant cells, the enhancement of this compound by verapamil was more likely due to inhibition of the MDR "pump." How, or whether, plasma membrane potentials and the MDR efflux "pump" are related remains to be investigated. In the resistant cells, verapamil also induced an increase (13-fold) in the accumulation of the electrically neutral fluorescent probe for calcium, INDO-1/AM. However, verapamil had no effect on the efflux of this compound, which was equivalent in both resistant and sensitive cells. Thus, a new effect of verapamil on drug accumulation in MDR cells is identified here. PMID- 2914016 TI - Inhibition by volume expansion of phosphate uptake by the renal proximal tubule brush border membrane. AB - Clearance studies and examination of brush border membrane (BBM) vesicle transport were performed in rats that had been volume expanded by 10% of body weight. The results were compared to those obtained in control animals. The data indicate that the phosphaturia which resulted from the expansion procedure was accompanied by an inhibition of proximal BBM phosphate uptake. The BBM uptake of proline and glucose was unchanged. Furthermore, since plasma calcium did not change, the findings are compatible with the view that the membrane transport changes resulted from alterations induced by the saline loading itself, rather than (or in addition to) any changes caused by parathyroid hormone excretion. PMID- 2914015 TI - Decreased estrogen hydroxylation in male rat liver following cimetidine treatment. AB - Administration of cimetidine (600 mumol/kg x 5) to adult male rats resulted in 55 and 25% decreases, respectively, in estradiol 2- and 16 alpha-hydroxylation. The same treatment also decreased the activities of ethylmorphine demethylase, aryl hydrocarbon hydroxylase, aniline hydroxylase and heme oxygenase but did not inhibit the activities of 7-ethoxycoumarin de-ethylase and delta-aminolevulinic acid synthase or decrease cytochrome P-450 content. In vitro addition of cimetidine (10-300 microM) also inhibited estradiol hydroxylations, and the effect was additive in rats pretreated with cimetidine in vivo; the other enzymic activities studied were completely unaffected by in vitro addition of cimetidine. In contrast, there was no effect of cimetidine either in vivo or in vitro on any of these activities in female rats. The results point to a wide variation in the susceptibilities of different isozymes of cytochrome P-450 to inhibition by cimetidine and suggest that such differential susceptibilities are also highly dependent on the sex of the animal. PMID- 2914017 TI - Drug-DNA dissociation kinetics. In vitro transcription and sodium dodecyl sulphate sequestration. AB - The rate of dissociation of actinomycin D from DNA was measured by sodium dodecyl sulphate (SDS) sequestration (37 degrees) from calf thymus DNA and a 24 base pair (bp) synthetic DNA containing one high affinity AGCT site for the drug. The time constants were 276 and 142 sec, respectively, and suggest a stabilising effect though positive cooperativity in heterogenous DNA, or from specific neighbouring sequences. The time constant for dissociation of actinomycin D from the AGCT site was 2900 sec as measured by an in vitro transcription assay at 37 degrees, and suggests that, under conditions of active transcription of the DNA, the drug-DNA complex has additional stabilising contributions, possibly by a cage effect from RNA polymerase, or by additional drug-RNA polymerase contacts. PMID- 2914018 TI - Effect of polyglutamylation of 5,10-methylenetetrahydrofolate on the binding of 5 fluoro-2'-deoxyuridylate to thymidylate synthase purified from a human colon adenocarcinoma xenograft. AB - CH2-H4PteGlu and H4PteGlu exist in human colon adenocarcinoma xenografts predominantly in the form of polyglutamate species at concentrations of less than 3 microM. The interaction of polyglutamates of [6R]CH2-H4PteGlu in the formation and stability of [6-3H]FdUMP-thymidylate synthase-CH2-H4PteGlun ternary complexes has therefore been examined using enzyme purified from a human colon adenocarcinoma xenograft. Dissociation of these complexes was first-order and was dependent upon the concentration of folate. [6R]CH2-H4PteGlu3-6 (0.9 to 1.6 microM) were greater than 200-fold and [6R]CH2-H4PteGlu2 (18.2 microM) was 18 fold more effective than [6R]CH2-H4PteGlu1 (335 microM) at stabilizing ternary complexes for a T1/2 for dissociation of 100 min. Polyglutamylation of CH2 H4PteGlu also increased the affinity of binding of [6-3H]FdUMP to thymidylate synthase as determined by Scatchard analysis at folate concentrations of 10 microM, where the Kd in the presence of [6R]CH2-H4PteGlu1 was in the order of 4.0 x 10(-8) M, and for [6R]CH2-H4PteGlu3-5 was between 3.7 and 5.5 x 10(-9) M. To examine whether this effect was due to differences in the rates at which [6 3H]FdUMP was bound (kon) or dissociated (koff) from the enzyme, the apparent rate of [6-3H]FdUMP binding was determined in the presence of [6R]CH2H4PteGlu1, [6R]CH2-H4PteGlu3 and [6R]CH2-H4PteGlu4. The kon values were similar and were in the range of 1.7 to 2.3 x 10(6) M-1 min-1 for 10 or 20 microM folate concentrations. Differences in binding affinity determined for [6R]CH2-H4PteGlu1 and longer polyglutamate forms of [6R]CH2-H4PteGlu were thus due to differences in koff. The Vmax for the initial velocity of [6-3H]FdUMP binding was achieved at 10 microM folate. Consequently, at concentrations of CH2-H4PteGlu polyglutamates present in tumors, inhibition of thymidylate synthase by FdUMP in vivo would be expected to be transient, based upon the concentration of [6R]CH2-H4PteGlun required for maximal formation and stability of the covalent ternary complex. It would be advantageous for modulation of CH2-H4PteGlun pools to increase the concentrations of the longer polyglutamate species (n greater than or equal to 3) to maximize the interaction between FdUMP, thymidylate synthase and CH2-H4PteGlu. PMID- 2914019 TI - Experimental values of the ionization constants for L-3,5-di-iodotyrosine and a model for ionic interactions of thyroid hormone (T3) and its nuclear receptor. AB - Ionization characteristics of L-3,5-di-iodotyrosine have been measured under various conditions. These data, which correct an erroneous report of pK3 in the literature, have been used to estimate the ionization constants of the thyroid hormone L-3',3,5-tri-iodothyronine (T3). On this basis a reinterpretation has been made of the pH-dependent binding of the hormone to its solubilized rat liver nuclear receptor (Wilson BD and Gent WL, Biochem J 232: 663-667, 1985). The interaction may depend on the ionization of the phenolic group of T3 and an acidic group (pK'7.6) in the receptor site, leading to the formation of a hydrogen bond between the two groups. The changes of the number of binding sites with pH must then result independently from alterations in the conformation of the receptor protein. PMID- 2914020 TI - Effect of D- or L-methionine and cysteine on the growth inhibitory effects of feeding 1% paracetamol to rats. AB - Rats fed 1% paracetamol in the diet failed to grow and a dose-dependent inhibition of growth was observed and found to be independent of hepatoxicity. Addition of 0.5% D- or L-methionine, or L-cysteine to a diet containing 1% paracetamol restored growth. Addition of L-methionine to the drinking water was equally effective. Feeding D-cysteine or sodium sulphate were ineffective. Acute paracetamol toxicity was also prevented by D- as well as by L-methionine. It is concluded that the inhibition of growth was due to depletion of sulphur amino acids in the course of paracetamol metabolism. This was sometimes followed by episodes of liver cell injury. Since the normal human dosage of paracetamol is up to 4 g/day, which is equivalent to 1% of the diet, the possibility of induction of amino acid deficiency by chronic use of paracetamol in normal dosage is raised. PMID- 2914021 TI - Properties of the microsomal and cytosolic glutathione transferases involved in hexachloro-1:3-butadiene conjugation. AB - Hexachloro-1,3-butadiene (HCBD) is a substrate for the hepatic microsomal glutathione transferases and is metabolised at higher rates by these enzymes than their cytosolic counterparts. Conjugation reactions catalysed by the microsomal and cytosolic transferases have been studied and characterized using this substrate and 1-chloro-2,4-dinitrobenzene (CDNB). In rat liver microsomes the Km values for HCBD and CDNB were 0.91 and 0.012 mM and in cytosol 0.51 and 0.10 mM respectively. Vmax values for HCBD were 1.39 and 0.35 nmol conjugate formed/min/mg protein for microsomes and cytosol respectively. In microsomal systems HCBD was a potent competitive inhibitor of the metabolism of CDNB with a Ki value of approximately 10 microM. However, CDNB did not inhibit HCBD metabolism significantly. These data suggest that more than one microsomal enzyme is involved in HCBD metabolism. The microsomal membrane could be solubilized without significant inhibition of HCBD activity; however, some detergents did inhibit the conjugation reaction. Activity was also lost on treatment of microsomal membranes with trypsin indicating the enzyme is localized on the cytoplasmic surface of the endoplasmic reticulum. Pretreatment of the rats with Aroclor 1254, 3-methylcholanthrene or phenobarbital did not change the microsomal conjugation of HCBD or CDNB with glutathione. Of seven species investigated, a human liver sample showed the highest ratio of microsomal to cytosolic glutathione transferase activity for HCBD (in microsomes 40-fold higher specific activity than in cytosol). Glutathione conjugation appears to play a critical role in the toxicity and carcinogenicity of some halogenated hydrocarbons. These data substantiate the potentially important role for the microsomal glutathione transferase in catalysing these reactions. PMID- 2914022 TI - Species differences in the effects of bezafibrate, a hypolipidemic agent, on hepatic peroxisome-associated enzymes. AB - The effects of bezafibrate on hepatic peroxisome-associated enzymes of rats, mice, guinea pigs, hamsters, rabbits, dogs and monkeys were examined. Dogs and monkeys were given bezafibrate orally at 30 mg/kg body wt daily for 2 weeks and at 125 mg/kg body wt daily for 13 weeks, respectively, and other species at 100 mg/kg daily for 2 weeks. In male rats, marked changes were observed in the activities of catalase (1.73-fold), D-amino acid oxidase (DAAO; 0.56-fold), fatty acyl-CoA oxidizing system (FAOS; 12.9-fold) and carnitine acetyltransferase (CAT; 35.8-fold); in female rats, the changes were less than in the males. In mice, there were no apparent sex differences in the responses of hepatic peroxisomal enzymes to bezafibrate and the increases in the activities of catalase, FAOS and CAT were 1.76-, 3.75- and 7.94-fold respectively. In guinea pigs, only slight increases in the activities of FAOS (3.00-fold) and CAT (2.83-fold) were observed. In hamsters, the increases in catalase, FAOS and CAT activities, were 1.23-, 2.19- and 2.77-fold respectively. Although rabbits and dogs showed slight increases in CAT activity, no significant response to the drug was observed in monkeys. Hepatomegaly and the increase of hepatic content of peroxisome proliferation-associated polypeptide (PPA-80), which has been recognized as a peroxisomal bifunctional protein in the fatty acid beta-oxidation pathway, were observed only in rats and mice. These results show that there were marked species differences in the effects of bezafibrate on hepatic peroxisomes, and that bezafibrate induced hepatic peroxisome proliferation in rodents, especially rats and mice. PMID- 2914023 TI - Platelet activating factor antagonist L-652,731 inhibits thymidine transport. PMID- 2914024 TI - Changes in polyamine content in primary cultures of adult rat hepatocytes. PMID- 2914025 TI - Effects of salicylate on rat liver in short-term toxicity studies. PMID- 2914026 TI - Services in the schools. Serving school children. Finding solutions and rewards in the educational setting. PMID- 2914027 TI - Software that works in school settings. A framework for choosing the right program. AB - The use of the computer as a tool in therapy is a relatively new concept. As with any new concept, there are many questions, concerns, and problems in implementation. Those who do not know how to use a computer should seek help from the individual in their school who is responsible for the care and maintenance of the computer equipment. A majority of software programs require very little knowledge about operating a computer. Those who do not have the funds to purchase needed software programs should request support from their school's PTA and community businesses, apply for a state or federal grant, or use a nearby college or university lending library. If local computer stores only carry business oriented software, software catalogues or computer magazines such as Teaching and Computers are sources for products. The magazines not only advertise but also critique software. Finally the computer application framework (Figure 1) should help clinicians determine how an individual piece of software can be chosen and implemented, based on a student's need and a clinician's work situation. No single piece of software is perfect for every student, nor is the public school environment perfect for the utilization of software. It is hoped that this article will help clinicians extract the best from both worlds by suggesting how the microcomputer can be used for therapy in a school setting. PMID- 2914028 TI - Atrial fibrillation induced by breath spray. PMID- 2914029 TI - Minorities, jobs, and health: an unmet promise. PMID- 2914030 TI - Occupational disease among minority workers: a common and preventable public health problem. AB - 1. Minority workers are overrepresented in the most hazardous jobs and, as a result, are at high risk of developing occupational diseases. 2. Due to various social and economic factors, minority workers with occupational diseases are less likely than white workers to come to health care attention and be correctly diagnosed as having an occupational disease. 3. Occupational health clinics and providers need to discuss options for treatment clearly with the client and, when appropriate, be persistent in negotiating with employers to reduce or eliminate harmful exposures, while remaining sensitive to the very real threat of job loss. PMID- 2914031 TI - Prevalence of hypertension in bus drivers. AB - 1. To test whether prevalence of hypertension was higher among these bus drivers than among employed individuals in general, drivers were compared to three groups: individuals from both a national and local health survey and individuals undergoing baseline health exams prior to employment as bus drivers. 2. After adjustment for age and race, hypertension rates for bus drivers were significantly greater than rates for the three comparison groups. 3. These findings support previous results from international studies of bus drivers suggesting that exposure to the occupation of driving a bus may carry increased health risk. PMID- 2914032 TI - Scope of practice. Part I. Case law. PMID- 2914033 TI - AAOHN position statement and action proposal. The registered care technologist. PMID- 2914035 TI - Use of computers in emergency medicine. PMID- 2914034 TI - A comparison of four methods of testing emergency medical technician triage skills. AB - Triage skills are requisite for all providers of prehospital care. Methods of assessing the acquisition of triage skills vary in complexity and expense. In this study, 61 prehospital care providers classified 20 cases, divided into four groups of five cases each: moulaged live trauma victims, nonmoulaged live trauma victims, nonmoulaged manikin trauma victims, and written scenarios. The providers were asked to classify the cases in each group by assigning triage tags to indicate injury severity and to rank the trauma victims in each group according to the urgency of care required. Analysis of variance revealed statistically significant differences among the four methods in both mean tagging scores (F3,235 = 8.63, P less than .0001) and mean ranking scores (F3,232 = 6.09, P less than .001). Multiple comparisons using Scheffe's test revealed that the mean tagging and ranking scores for moulaged live victims and written scenario methods were comparable and that both were significantly superior to the scores of the two other methods. However, a qualitative evaluation revealed that the providers greatly preferred triage of moulaged live victims to the other three methods. PMID- 2914036 TI - Toxic smoke inhalation. PMID- 2914037 TI - Distant injury pneumothorax. PMID- 2914038 TI - Acute hydrofluoric acid exposure. PMID- 2914039 TI - Magnesium sulfate termination of torsades de pointes following failure of cardioversion. PMID- 2914040 TI - Seizure associated with low-dose naloxone. PMID- 2914041 TI - Sudden death temporally related to vaginal cocaine abuse. PMID- 2914042 TI - A national survey of pediatric emergency medicine: a growing subspecialty. PMID- 2914043 TI - Emergency department detection and follow-up of high blood pressure: use and effectiveness of community health workers. AB - This study introduced trained paraprofessionals, community health workers (CHWs), into the emergency department (ED) to supplement providers' routine efforts in high blood pressure (HBP) detection, treatment, and follow-up among high-risk black men. In a demonstration project over a 2-year period, CHWs provided (1) BP and pulse measurements, and educational counseling regarding HBP and cardiovascular risk factors; (2) telephone preappointment reminders to improve ED follow-up visit rates; and (3) recontact of patients failing to show for their ED follow-up visits to improve return rates even after missed BP appointments. Results of preappointment reminders by CHWs showed a 19% improvement in appointment keeping (P less than .001). With a sample of patients who had failed to return for a follow-up visit, CHW contact was also effective, showing an overall improvement rate of 7% (P less than .001). The results reported support the idea that individuals from the community, trained as paraprofessionals, can improve appointment keeping as well as be useful in assisting in screening and counseling for chronic conditions within the ED. These CHWs are seen as having the additional advantage of enhancing the integration of the ED, the community, and continuing care sites. The approaches used in this study should be applicable and may serve as a model for the approach to other chronic conditions experienced in urban high-risk communities. PMID- 2914044 TI - Regional use of violent suicide methods: an analysis of suicide attempts in Houston, Texas. AB - A number of changes in the demographics of suicide and suicide attempters have occurred in the last 10 to 15 years. To assess some of the factors that may be involved in these changes, this study examines a group of suicide attempters in Houston, Texas, where a large percentage of the attempts were violent. These violent attempters are compared with nonviolent attempters, and the entire population of attempters is compared with suicide attempters in New Haven, Connecticut. Finally, the two attempter populations are compared with the underlying general population demographics of two regions (Houston and New Haven). Several differences emerged between attempters in Houston and in New Haven, including larger proportions of violent attempters, male attempters, and married attempters in Houston. Demographic factors in the general populations for the two regions are different, but these differences are not directly reflected in the nature of the attempter populations. Reasons for observed differences are discussed. PMID- 2914045 TI - Concrete impaction of the external auditory canal. AB - A case of accidental impaction of the external auditory canal by concrete in a construction worker seen at Orlando Regional Medical Center is reported. A general discussion of the pathophysiology of concrete-related injuries is included. Recommendations are made for the optimal emergency management of these type injuries. PMID- 2914046 TI - Magnesium toxicity secondary to catharsis during management of theophylline poisoning. AB - Multiple doses of oral activated charcoal are used increasingly to promote elimination of toxins that have already reached the bloodstream; this is often referred to as gastrointestinal dialysis. Cathartics usually are used in conjunction to hasten transit of the charcoal-adsorbed toxin. In the present case, a regimen of activated charcoal and magnesium citrate was used to treat a patient with theophylline poisoning. It was effective in lowering the patient's serum theophylline concentration but produced an elevated magnesium level associated with decreased responsiveness, confusion, and diminished deep tendon reflexes. Magnesium citrate may not be the optimal cathartic for use in gastrointestinal dialysis, at least in selected patients. Sorbitol has been shown to produce a more rapid catharsis without disturbing magnesium serum concentrations. Therefore, the use of sorbitol in place of magnesium citrate, at least in selected patients, may be preferred. PMID- 2914047 TI - The generation of acetonemia/acetonuria following ingestion of a subtoxic dose of isopropyl alcohol. AB - A subtoxic dose of isopropyl alcohol was ingested by three subjects to evaluate the time to and extent of acetone generation and to explore its detection in the urine. Maximal serum isopropyl alcohol concentrations were observed by 30 minutes after ingestion of approximately 1 oz 70% isopropyl alcohol (0.4 mL/kg), but maximal serum acetone concentrations were not recorded until at least four hours postingestion. Urine tested positive (small) for acetone within three hours of ingestion using Acetest urine testing tablets (Ames Labs, Elkhart, IN). It was concluded that acetonemia occurs early after ingestion of isopropyl alcohol and increases as serum isopropyl alcohol concentrations decline. In addition, acetonuria may be qualitatively measured by three hours postingestion with rapid urine screening tests and may remain positive for 24 hours. PMID- 2914048 TI - Clinical features and consequences of seizures due to cyclic antidepressant overdose. AB - The charts of 30 patients with seizures caused by cyclic antidepressant toxicity were reviewed to determine the natural history of these seizures and their effect on outcome. Mortality was 10%. Onset of seizures was within 1.5 hours of admission in all but two patients. Both patients with seizures occurring later than 1.5 hours had also ingested ethanol. Antecedent mental status did not predict the occurrence of seizures; 23% of seizures occurred when patients were alert. The majority of patients (25 of 30) had one or two brief (less than 2 minute), self-limited, generalized, tonic/clonic seizures that terminated without anticonvulsant therapy. Six patients had prolonged or repetitive seizures. Most seizures, even when multiple or sustained, had no sequela. However, four patients developed marked cardiovascular deterioration immediately following seizures, with hypotension and ventricular tachycardia or bradyarrhythmias. All four had a QRS duration greater than 200 msec at some time during their hospitalization. It is concluded that most seizures associated with cyclic antidepressant toxicity occur soon after admission, are brief, and terminate without specific anticonvulsant therapy. Even when brief, however, seizures may occasionally lead to abrupt cardiovascular deterioration and death. It is not clear which patients are at risk for severe cardiovascular complications. PMID- 2914049 TI - Cervical spine injury masquerading as a medical emergency. AB - Two cases of cervical spine fractures presenting as cardiac arrest in one case and as a coma with pneumonia and cervical osteomyelitis in the other are discussed. They demonstrate the need for careful history taking as well as a cautious approach to the cervical spine when accurate historical data are not available. PMID- 2914050 TI - Ventricular fibrillation during rectal examination. AB - The case of a 74-year-old man who developed ventricular fibrillation during a digital rectal examination is presented. The patient was subsequently resuscitated and developed cardiac enzyme elevation without ECG changes, indicating a nontransmural myocardial infarction. Although controlled studies have not shown any ill effects of rectal examination in patients with acute myocardial infarction, there have been multiple case reports of bradycardia, ectopy, and ventricular arrhythmias resulting from rectal examination. The postulated etiology of the ectopy is twofold; increased vagal tone from rectal parasympathetic innervation or increased sympathetic tone from anxiety-stimulated catecholamine release. Rectal examination is definitely indicated in a subset of patients including those with gastrointestinal or genitourinary complaints, unexplained hypotension or anemia, trauma, and neurological deficits, and those who will receive anticoagulation or thrombolytic therapy. In the remaining patients, the decision must be made on a case-by-case basis. Awareness of and precautions for possible ill effects of the examination are prudent. PMID- 2914052 TI - Changing environment and the academic medical center: the Johns Hopkins School of Medicine. AB - Both academic and economic goals must be served by the academic health center. In response to ongoing stresses on medicine, the Johns Hopkins School of Medicine and the Johns Hopkins Hospital rapidly developed and implemented an expanded system of medical care. Vertical integration included provision of both acute and chronic care facilities and both primary and specialty care, as well as insurance products, in particular a health maintenance organization. Horizontal integration was accomplished by acquisition of or affiliation with other hospitals. The realignment of medical resources and patients shifted the locus of medical education somewhat, from the traditional hospital setting to the ambulatory care setting (in which many students and residents will eventually practice anyway). In addition, many physicians in the new settings are not traditional Johns Hopkins faculty members. Results of educational efforts in these altered circumstances so far have been mixed, partly because the capacity of the individual center to train students and residents is necessarily limited, and the fragmentation of the system makes inevitable problems of quality control and management. These issues are being worked out. The drain on faculty resources for research imposed by the need to expand clinical practice has been offset by a system of awards for research to faculty members. Efforts are being made to sustain the excellence of the traditional Johns Hopkins faculty's reputation while assuring doctors newly affiliated with the Hopkins system that they are no less important to the system. Opportunities to learn and to teach more economical medicine while retaining quality are discussed. PMID- 2914051 TI - Pediatric and adult emergency management assistance using computerized guidelines. AB - This study was performed to determine if computer assistance is able to improve the initial management of pediatric patients in critical emergencies. A computer program that provides an easily accessible, concise set of information to assist in the management of medical emergencies is described. It provides size- and age specific endotracheal tube sizes, drug doses, continuous intravenous (IV) drug infusion preparation instructions, and emergency management guidelines for pediatric and adult patients with one of several acute emergencies. These emergencies include asystole, respiratory failure, anaphylaxis, shock, myocardial infarction, cardiac arrhythmias, seizures due to several common causes, and rapid sequence anesthesia induction. The use of this program was shown to reduce the time required for the preparation and administration of emergency therapy while minimizing management errors. A lap-top computer running this program may be a worthwhile addition to emergency departments and hospital resuscitation carts as a resource, especially for physicians less experienced in the care of children. PMID- 2914053 TI - The difficulty of diffusing innovations. PMID- 2914054 TI - International health. PMID- 2914055 TI - Recent W. K. Kellogg Foundation initiatives in medical education. PMID- 2914056 TI - Future health opportunities--the 101st Congress. PMID- 2914058 TI - Alternatives to animal use. PMID- 2914057 TI - Resident stress: sleep deprivation. PMID- 2914059 TI - Training for foreign medical graduates. PMID- 2914060 TI - Effect of a major curriculum revision on students' perceptions of well-being. AB - The impact of a major curriculum revision on students' perceptions of the quality of the medical school learning environment, social supports, and their own mental and social well-being was determined. First-year students' perceptions one year before the curriculum revision were compared with first-year students' perceptions two years after the introduction of the new curriculum. In the new curriculum, students reported better overall quality of the learning environment (p = .019), a trend toward fewer stresses (p = .091), no difference in social supports (p = .721), better mental well-being (p = .043), and a trend toward better social well-being (p = .099). Students at a comparison school that did not undergo curriculum revision did not have more favorable perceptions during the study period. The findings suggest that well-considered and well-executed efforts to improve the quality of a medical school's learning environment can be successful and can raise students' perceptions of their overall well-being. PMID- 2914061 TI - Effects of sleep deprivation on cognitive ability and skills of pediatrics residents. AB - The stress and long working hours of medical residency have become the basis for controversy over whether current training structures and processes adversely affect residents' skills and well-being and the quality of patient care. The authors measured cognitive and skills performances of 45 sleep-deprived pediatrics residents by using questions like those on the pediatrics board certification examination and using patient-care tasks that required coordination and dexterity. The residents were randomly divided into two groups--one stayed awake for 24 hours, the other for 34 hours--and were tested on cognitive and skills performances before and after sleep deprivation. Sleep deprivation did not have a significant effect on cognitive performance. Of the three skills tested, the residents overall needed more time to perform umbilical artery catheterization, but the group deprived of sleep for 34 hours performed vein cannulation more quickly than the group deprived for 24 hours. Implications for these findings are discussed in the context of the ongoing controversy over the structure and process of medical education. PMID- 2914062 TI - Prior training and recommendations for future training of clinical research faculty members. AB - A survey was conducted of the first authors of half of the research papers published in 18 leading peer-reviewed medical journals over a six-month period in 1986. The first authors of every other article (that is, alternate articles) published during this period were sent a questionnaire that assessed their previous research training and their recommendations for training of clinical research faculty members. Of the 772 physicians sent the questionnaire, 482 responded. Of these, 57% had had some research training in medical school, 52% had received such training during residency, and 87% had received it during their fellowships. Fifty-six percent had taken a formal statistics course, 31.4% had taken some computer training, and 87% had received research supervision in a nonstructured format (that is, no formal course work). Introductory biostatistics was the only formal course in any of the seven subject areas listed in the questionnaire that more than one-third of the respondents had taken, yet at least two-thirds recommended that researchers take formal courses in all of the seven areas listed. The investigators recommend for medical students and postgraduate trainees a graduated experience of research training and exposure that includes formal courses. PMID- 2914063 TI - Teaching medical students in ambulatory settings in departments of internal medicine. AB - Clinical training in ambulatory settings is an increasingly prominent topic in medical education, but most descriptions of internal medicine programs in the literature concern training for residents. The authors undertook a survey of departments of internal medicine to obtain and assess information about requirements for ambulatory clinical experiences for medical students. The results show that few departments (24% of the 101 departments responding) required ambulatory care experiences for undergraduates. Most of the required programs had a goal of broad exposure to ambulatory-patient problems; almost none had special educational interventions to complement students' care of patients. The experiences that were incorporated into the clerkship in a single block of time were more favorably rated than the experiences that occurred intermittently throughout the clerkship. Inability to provide continuity-of-care experience was an important concern of the departments. Most programs had logistical problems, the most serious and frequently cited being the lack of faculty time for teaching. The authors raise concerns about the educational effectiveness of many existing programs and, given the problems with faculty involvement, about the long-term viability of these programs. PMID- 2914064 TI - Noncognitive criteria for assessing students in North American medical schools. AB - In 1986 the authors mailed a one-page questionnaire to 135 North American medical schools requesting information about written expectations for students that contain noncognitive criteria. Eighty-eight questionnaires (65.2%) were returned, and 48 schools (54.5%) indicated they possessed written noncognitive criteria. Those schools having noncognitive criteria were asked to submit the criteria for review and were questioned about their reasons for establishing such criteria. Those schools not having noncognitive criteria were asked whether they perceived a need for such criteria and had plans for developing them. The study showed an increasing trend to create criteria that assist in administrative actions when problems arise. In the 31 sets of noncognitive criteria submitted for the study, the rank order of specific expectations was, from most to least frequently mentioned: honesty, professional behavior, dedication to learning, appearance, respect for law, respect for others, confidentiality, aid to others, substance abuse, and financial responsibility. The authors make recommendations for schools wishing to create noncognitive criteria and explain why they feel such criteria should receive the recognition and importance given to cognitive criteria. PMID- 2914065 TI - A program of management training for residents. AB - To help prepare residents in preventive medicine and occupational medicine for their future management roles, the University of Arizona College of Medicine incorporated administrative training into many aspects of its residency programs, beginning in 1983. Training focuses on seven skill areas seen as needed to meet the management demands of the physicians' future specialties. The authors discuss the career choices of University of Arizona graduates and advocate long-term administrative training for all specialties. PMID- 2914066 TI - Attribution of control in psychiatric residents. AB - At quarterly intervals in 1986-87, attribution of control and subjective symptom ratings were assessed among the 42 general psychiatry residents in the University of Cincinnati's training program. Within each of the four groups of residents (that is, the residents in each postgraduate year), ratings remained stable over time. Between-group differences were significant for ratings of internal locus of control, but the external locus of control ratings showed no corresponding fluctuation. The internal locus of control scores were inversely correlated with psychological distress as reported in the Brief Symptom Inventory. PMID- 2914067 TI - Evaluation of emergency medicine residents by nurses. AB - Emergency medicine residents at William Beaumont Hospital are evaluated quarterly by the nursing staff. The nurse discuss each resident and reach consensus on each evaluation item. Copies of the evaluations are given to each resident, and a copy is used at the resident's biannual evaluation meeting with the program director. Between September 1985 and December 1987, 45 residents in all three years of training were evaluated by the nursing staff on four aspects of performance: managerial skills, communication, teamwork, and clinical organization. The nurses were able to evaluate behavior not usually seen by supervising physicians. Although the residents' attitudes toward these evaluations have not been entirely favorable, overall their behavioral interactions have improved markedly. PMID- 2914069 TI - A useful and cost-effective way to provide feedback from students to community physician preceptors. PMID- 2914068 TI - A course in diagnostic test evaluation for senior medical students. PMID- 2914070 TI - Changing environment and the academic medical center: the Johns Hopkins Hospital. AB - Academic medical centers need strong patient bases and strong financial bases to educate and to support research. After careful delineation of its mission with regard to patient care, research, and education, the Johns Hopkins Hospital expanded its health care delivery capabilities and strengthened its position in the health care marketplace by acquisitions of and mergers with other hospitals and a health maintenance organization in the Baltimore area. The resulting conglomerate, operating under the direction of a holding company, the Johns Hopkins Health System, has achieved its goals of expanding patient care capabilities, broadening the patient base, and enlarging the asset base and cash flow. Half the medical residents at the Johns Hopkins School of Medicine receive training at nontraditional sites, and further expansion of teaching activities is being explored. Potential roles of traditional and nontraditional teachers in these activities are discussed. PMID- 2914071 TI - Sensory evidence for olfactory receptors with opposite chiral selectivity. AB - Human odor responses to alpha-ionone enantiomers were measured by psycho-physical methods. Surprisingly, subjects' relative sensitivities for these enantiomers were found to diverge widely, some subjects being much more sensitive to (+) than to (-) and vice versa. In 63 subjects the (+)/(-) threshold concentration ratio varied over 4 orders of magnitude. Nine subjects with extreme (+)/(-) ratios were further tested several times over a 7-month period and retained stable ratios. These same nine subjects, when tested for threshold sensitivity to carvone enantiomers, showed (+)/(-) ratios that varied only in a narrow range and did not correlate with their ionone ratios. It is suggested that odor discrimination of alpha-ionone enantiomers involves at least two receptor types of opposite chiral selectivity and that their distribution varies independently in the human population. PMID- 2914072 TI - A comparison of the effects of fornix transection and sulcus principalis ablation upon spatial learning by monkeys. AB - In each of three experiments with Cynomolgus monkeys (Macaca fascicularis), there was a group of normal control animals, a group with bilateral cortical ablations in the principal sulcus, and a group with fornix transection. In Expt. 1, half of each group learned problems in which the position of a pair of visual stimuli, to the monkey's left or right, indicated which of the visual stimuli was the correct (rewarded) one. The other animals learned problems in which visual stimuli indicated, irrespective of their own spatial position, whether reward was to be found on the monkey's left or on the right. The animals with fornix transection were impaired in both tasks. The animals with sulcus principalis ablation were also impaired in both tasks. The impairment caused by fornix transection was more severe than that caused by sulcus principalis ablation. Within each of the two operated groups, the degree of impairment in the two tasks was equal, when assessed in proportion to the difficulty of each task for control animals. Expt. 2 showed that neither of the operated groups was impaired in visual discrimination learning with spatial position irrelevant. Expt. 3 tested spatial discrimination learning (acquisition and reversal of a left-right discrimination) with irrelevant visual cues. Here the fornix-transected group was impaired but the group with sulcus principalis ablations was normal. It is suggested, on the basis of these findings and previous results, that fornix transection produces a general deficit in remembering the spatial arrangement of whole scenes, while sulcus principalis ablation produces a deficit in high-order integration involving spatial information. PMID- 2914073 TI - Enhanced detection of nucleus basalis magnocellularis lesion-induced spatial learning deficit in rats by modification of training regimen. AB - Bilateral excitotoxic lesions of the nucleus basalis magnocellularis (NBM) in the rat cause deficits in the water maze, a spatial memory paradigm. Previous investigations aimed at reversing the water maze performance deficit with anticholinesterase treatments have been unable to demonstrate a consistent drug effect due to the relatively good acquisition of the task seen following NBM lesions. The present investigation tested three different water maze training regimens designed to separate the learning curves. F-344 rats received bilateral NBM injections of ibotenic acid; sham-operated rats served as controls. The animals were tested in three groups in the water maze as follows: (1) four trials per day with no intertrial interval (standard paradigm), (2) four trials per day with a 10-minute intertrial interval, and (3) two trials per day with no intertrial interval. Each group was tested in the water maze for five consecutive days, followed by two days of rest, and then tested for an additional five days. The two-trial per day paradigm was more difficult than the standard paradigm for both lesions and controls and yielded the most difference between lesions and controls as compared to the other two testing regimens. The 10-min intertrial interval schedule was more difficult than the standard paradigm for lesioned animals but acquisition was not affected in control rats. These data demonstrate that the nucleus basalis lesions cause a deficit in the water maze task regardless of training parameters. Further, while all rats showed some acquisition of the water maze task, training schedule affected the level of learning of both lesioned and control rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2914074 TI - The effects of ibotenic acid lesions of the nucleus accumbens on spatial learning and extinction in the rat. AB - Rats with ibotenic acid lesions of the nucleus accumbens (N. Acc) were studied in two spatial learning paradigms: a T-maze and a Morris water maze. Learning of a spatial discrimination task and its reversal in the T-maze were disrupted by the N. Acc lesions. As both original and reversal learning were impaired, there was no evidence of a specific lesion effect on reversal learning. The lesioned rats did not perseverate excessively in their choice of the previously reinforced arm. There was evidence of behavioural inflexibility during extinction when the lesioned rats failed to slow the pace at which they ran the maze in the absence of reward. Spontaneous alternation was not significantly affected by the lesion. Acquisition of the second spatial task, locating the hidden platform in the Morris water maze, was also impaired. The lesioned rats did eventually learn the task and successfully reached the platform with similar latencies and heading errors to controls. Thus, the N. Acc lesion impaired but did not abolish spatial learning in the T-maze and the water maze. The deficits observed in this study may reflect a role for the N. Acc in the reorganisation of behaviour in response to external change. PMID- 2914075 TI - Effects of lesions of the dorsal noradrenergic bundle on conditioned suppression to a CS and to a contextual background stimulus. AB - The aim of the experiment was to determine whether the dorsal noradrenergic bundle (DB) plays a role in conditioning to context. Rats received either bilateral lesions of the DB by local injection of 6-hydroxydopamine, vehicle injections only, or sham operations. All animals were then trained to barpress for food on a variable interval (VI) schedule. Two 5-min intrusion periods were superimposed on the VI baseline during each session. An 'envelope' stimulus (flashing light) was on throughout each intrusion period. In addition, embedded in the two intrusion periods of each session, there occurred 8 presentations of a 'punctate' conditioned stimulus (CS) (a 15-s clicker), and 8 presentations of a 0.5-s footshock. Within each surgical condition rats were randomly allocated to one of three conditioning groups, receiving 100%, 50% or 0% temporal association between CS and shock. Conditioning to the punctate CS and to the context provided by the envelope stimulus was assessed by the degree of suppression of the barpress response relative to the VI baseline. Responding was most suppressed in the punctate CS in the 100 and 50% conditions, and most suppressed in the envelope stimulus in the 0% condition. DB lesions released response suppression to the punctate CS, had no effect on suppression to the envelope stimulus, and reduced sensitivity to CS-shock probability as measured by response suppression during the punctate CS. These results confirm previous reports that DB lesions alleviate response suppression to shock-associated cues, identify some of the parameters that affect this phenomenon, but fail to support a role for the DB in contextual conditioning. PMID- 2914076 TI - The role of the lateral cortico-cortical prefrontal pathway in self-stimulation of the medial prefrontal cortex in the rat. AB - Effects of electrolytic and kainic acid lesions at several stereotaxic planes of the lateral cortico-cortical prefrontal efferent pathway on self-stimulation of the medial prefrontal cortex were investigated. Electrolytic bilateral lesion of the sulcal prefrontal cortex, the first terminal area of this pathway, produced no effects on self-stimulation of the medial prefrontal cortex. However, bilateral electrolytic lesion of this pathway at the rostral part of the external capsule produced a permanent abolition of self-stimulation of the medial prefrontal cortex. These effects seemed selective since operant behaviour to obtain water, similar to that performed for self-stimulation and used as a control, was not affected by the lesion except on the 1st, 3rd (P less than 0.01) and 5th (P less than 0.05) days postlesion. Interestingly, bilateral microinjections of kainic acid (10 nmol in 0.8 microliters) at the same stereotaxic planes of the external capsule where electrolytic lesion was produced, had no effects on self-stimulation. These results suggest that fibres of-passage through the external capsule are responsible for the abolition of self stimulation. Bilateral electrolytic lesion of the entorhinal cortex, one of the caudal terminal areas of this descending set of fibres, produced a short transient decrease of self-stimulation of the medial prefrontal cortex. These results are discussed on the basis that complex, rather than single circuits are involved in maintaining self-stimulation in this neocortical area. PMID- 2914077 TI - Circling behavior: ethological analysis and functional considerations. AB - Head-turning and circling movements evoked by substantia nigra (pars compacta) (SNpc) stimulation have been ethologically analyzed in order to attribute a functional meaning to these lateralization processes. It has been shown that these motor acts, separated by a constant interval, may be considered a fixed action pattern. The duration of the single acts depends on the SNpc stimulation parameters: the increase in the stimulus strength produces an increase in the number of turns but does not induce the disappearance of the orientation movement. The body movement is always preceded by the head-movement. Haloperidol administration induces a dose-related increase of the orientation component of the motor pattern. These data together with others in the literature suggest the participation of the SNpc in the mechanism of shift in the focus of attention from one point to another in the contralateral surrounding environment. PMID- 2914078 TI - The influence of dopaminergic A10 neurons on the motor pattern evoked by substantia nigra (pars compacta) stimulation. AB - The influence of the mesolimbic-mesocortical dopaminergic (DA) system on the motor pattern evoked by substantia nigra pars compacta (SNpc) stimulation was studied. Electrical stimulation of the A10 group of neurons caused an inhibitory effect preferentially directed towards the orientation movement. Sulpiride administration at low dosages (50 mg/kg i.p.) did not modify this movement at the basal condition, but abolished the increase of its duration induced by ventral tegmental area (VTA) co-stimulation. Mesolimbic activation opposes the effects of SNpc stimulation, restraining the animal in its antero-posterior axis by means of orientation movement inhibition. The results suggest a role of the DA mesolimbic mesocortical system in the maintenance of focused attention. PMID- 2914079 TI - Kindling facilitates acquisition of discriminative responding but disrupts reversal learning of the rabbit nictitating membrane response. AB - The effect of kindling the hippocampal perforant path-dentate projection on subsequent discrimination-reversal conditioning of the rabbit nictitating membrane (NM) response was examined. Kindling facilitated acquisition of the initial discriminative response but severely impaired performance during reversal training. The facilitative effect on initial acquisition is highly similar to previously reported effects of long-term potentiation on NM discrimination learning, and thus may reflect a kindling-induced increase in perforant path dentate synaptic strength. The learning deficit during reversal training is similar to the effects of hippocampal ablation; i.e. characterized by a continued high response rate to the CS- rather than an inability to respond to the CS +. These findings demonstrate that kindling-induced seizures can have profound effects on associative learning. The effects are different for the discrimination and reversal phases of the task, however, which may reflect the multi-dimensional effects of kindling at the cellular level. PMID- 2914080 TI - Rats can learn a roughness discrimination using only their vibrissal system. AB - Rats learned to discriminate between two degrees of roughness, detecting the stimuli only with their vibrissal system. After bilateral trimming of the vibrissae, performance abruptly dropped to chance levels and remained there throughout the period in which the vibrissae were kept trimmed. After the vibrissae regrew to approximately normal lengths, rats again exhibited high performance levels and demonstrated retention of the task. This discriminative procedure would appear to be appropriate for psychophysical assessment of vibrissal system function. PMID- 2914081 TI - Direct and transcallosal contribution to the cortical visual evoked response in rats. AB - The averaged visually evoked cortical potential (VECP) in response to contrast reversal of a grating was measured on striate cortex over a range of spatial frequencies and contrasts. The response to binocular or monocular stimulation was almost abolished by unilateral section of the optic tract on the side of the recording, indicating that the transcallosal pathway makes little contribution to the VECP. Additional section of the corpus callosum, and application of spreading depression to the normal hemisphere shows that the small response following tract section was transcallosal. It was confined to stimuli of low spatial frequencies and high contrast. PMID- 2914082 TI - Effects of oral calcium, potassium, digoxin, and nifedipine on natriuresis in normal humans. AB - Many factors influence renal sodium excretion and blood pressure. We tested the independent effects of dietary calcium (Ca; 500 mg twice daily), potassium (KCl; 20 mEq three times daily), sodium-potassium dependent ATPase inhibition (digoxin), calcium channel blockade (nifedipine), and placebo, on acute natriuresis in 14 normal subjects while receiving 150 mEq/d sodium diets and 2 L normal saline intravenously over four hours. Each subject received each regimen in random sequence. Sodium balance before infusion was not different among the regimens. Plasma renin activity (PRA) was increased in subjects receiving nifedipine, while the plasma aldosterone concentration (PA) was not different among the regimens. None of the regimens influenced the clearance of inulin or paraaminohippurate (PAH) either before or after saline infusion. Only KCl and nifedipine affected sodium excretion compared to controls. KCl and nifedipine increased the amount of sodium excreted after the infusion was terminated. In the case of nifedipine, this natriuresis was sufficient to increase the 24-hour sodium excretion on that day to above that of the other regimens. The data support the notion that potassium and nifedipine may decrease blood pressure by facilitating sodium excretion. Nifedipine may also uncouple renin from aldosterone. Oral calcium supplementation and sodium-potassium dependent ATPase inhibition did not facilitate natriuresis. PMID- 2914083 TI - Effects of spontaneously hypertensive rat plasma on blood pressure and tail artery calcium uptake in normotensive rats. AB - Previous studies have described the presence of humoral hypertensive factors in spontaneously hypertensive rats (SHR). Other studies have described factors that increase calcium uptake in vascular tissue. In this study, we attempted to confirm, and thereby correlate, the presence of both types of factors in SHR plasma. Intravenous infusion or bolus administration of dialyzed SHR plasma consistently induced an increase in blood pressure in normotensive rats. This hypertensive response was somewhat delayed, with peak blood pressures occurring 45 minutes after bolus administration and 90 minutes after infusion of SHR plasma. Spontaneously hypertensive rat plasma also increased 45Ca uptake in isolated normotensive rat tail arteries in a dose-dependent manner, with a time course similar to that for the hypertensive response to bolus administration. These findings suggest, therefore, that a substance exists in SHR plasma that can increase intracellular calcium in vascular tissues and thereby increase blood pressure. PMID- 2914084 TI - Cultured hypothalamic explants from spontaneously hypertensive rats have decreased vasopressin and oxytocin content and release. AB - To investigate the central nervous system (CNS) changes in the spontaneously hypertensive rat (SHR), a tissue culture model was used to examine the content and release (24 hour) of the peptide hormones, vasopressin (VP) and oxytocin (OT), from brain explants. Nuclear regions consisting of the paraventricular (PVN) or supraoptic (SON) nuclei were microdissected from prehypertensive SHR and Wistar-Kyoto (WKY) rats. Media levels of VP and OT were measured at 1, 3, 4, and 7 days of culture. After three days of culture, the PVN explants from SHR secreted significantly less VP and OT (both reduced 80%) than did those from WKY. Release of both VP and OT in the SON explants was significantly lower (approximately 50% lower) in the SHR only at seven days of culture. Additionally, tissue content of the peptides was measured after 0, 1, 4, and 7 days of culture. Tissue content of VP and OT was decreased (40% or more) in the SHR in both nuclear regions after four and seven days of culture. In addition, nicotine was found to stimulate the release of VP from SON, but not PVN, cultures in both SHR and WKY explants. Immunohistochemical data showed that there was not a preferential loss of VP or OT neurons in explants from the SHR. Therefore, this in vitro model would indicate that there is a difference in the ability of cultured explants of PVN and SON from SHR and WKY (four-week-old) to synthesize and/or release the peptide hormones VP and OT. PMID- 2914085 TI - Forearm hemodynamics at rest and stress in borderline hypertensive adolescents. AB - Cardiovascular adaptations to mild elevations of blood pressure (BP) may occur early in the development of essential hypertension (EH). We used strain gauge plethysmography to study forearm hemodynamics in adolescents. Ten normotensive males (N) were compared to ten males with borderline hypertension (H). Measurements of forearm blood flow (FBF) were obtained after supine rest, during ten minutes of mental stress (mental arithmetic) and five minutes post stress. Mean arterial pressure (MAP) and forearm vascular resistance (FVR) were calculated. The H maintained higher MAP and FVR (P less than or equal to .05) throughout the study. The vascular response patterns were assessed by comparing the slopes of the linear regression equation FBF = a ln FVR + b (where a = slope and b = intercept). From baseline to stress, the N exhibit a significant change in slope (P less than .05), shifting to a decrease in FVR per unit FBF change. However, the H maintain a constant slope and FVR per unit FBF change remains constant. The study suggests that a primary peripheral vascular abnormality may be present even in the young with marginally elevated BP. PMID- 2914086 TI - Risk factors for glomerular injury in rats with genetic hypertension. AB - Systemic and glomerular hypertension, hyperlipidemia, and massive proteinuria have been described as risk factors for the development of focal glomerulosclerosis (FGS). Previous studies have shown that Dahl salt-sensitive (S) rats with severe hypertension have elevated glomerular pressures and develop extensive FGS. In the present study, we determined whether Dahl S rats exhibit other risk factors for FGS. Dahl S rats were found to have elevated serum triglycerides at six weeks of age, compared to Dahl salt-resistant (R) rats. Between six and 24 weeks, systemic hypertension and progressive increases in both serum lipids and albuminuria occurred in Dahl S rats fed high salt (4% NaCl) chow. No changes in blood pressure or serum lipids occurred in Dahl R rats fed high salt. At 30 weeks, the incidence of FGS was 20 times greater in hypertensive Dahl S than in Dahl R. In a separate study, we compared risk factors for FGS in Dahl S rats and spontaneously hypertensive rats (SHR). The magnitude of glomerular capillary pressure, serum lipid levels, and urine albumin excretion were measured in male Dahl S rats and male SHR between 12 and 20 weeks of age. Normal values for the various parameters were established in a group of normotensive male Sprague-Dawley rats. For this study, all rats were fed standard chow containing 0.6% NaCl. Blood pressure was elevated (P less than .01) in Dahl S (142 +/- 2 mm Hg) and in SHR (173 +/- 3 mm Hg) compared to the Sprague-Dawley rats (117 +/- 3 mm Hg). Glomerular capillary pressure, however, was similar in all three groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2914087 TI - The versatile midforehead browlift. AB - Ptosis of the brow is a significant and often unrecognized portion of aging of the upper face. It contributes to both cosmetic and functional aging. Correction is often mandatory prior to blepharoplasty in that functional problems may be worsened without elevating the brow. Direct and coronal browlifts are the most common approach to the problem. Midforehead browlifts have been reserved for men with receding hairlines. We have, for the past three years, performed midforehead browlifts on all our patients needing ptotic brow correction. Our review of 72 patients treated in this way, including 52 women, shows excellent and long lasting cosmetic and functional improvement. There have been few complications, and the resultant incisional scars have been very well accepted. Therefore, we feel that the midforehead browlift, performed as we describe, is the ideal surgical correction for the ptotic brow. PMID- 2914088 TI - The effects of pentoxifylline on random skin flap survival. AB - Random skin flaps are an important and frequently used technique in head and neck reconstruction. Pentoxifylline has been shown to improve the deformability of red blood cells by increasing their intracellular adenosine triphosphate content and, therefore, improving their flow properties. This is especially important in ischemia and low blood flow states present in the distal portions of random skin flaps. The rheologic properties of pentoxifylline were studied in the swine model. Swine in group I (eight flaps) served as controls with no pharmacologic manipulations. Swine in group II (16 flaps) received pentoxifylline (20 mg/kg/d) for ten days preoperatively and ten days postoperatively. Necrosis in swine in group I (controls) averaged 32.6%, which substantiated previous reports. Necrosis in swine in group II (pentoxifylline) averaged 2.57%. This study has shown a statistically significant enhancement of random skin flap survival using pentoxifylline in a swine model. PMID- 2914089 TI - Acute blood flow changes in rapidly expanded and adjacent skin. AB - Random flaps raised in expanded skin demonstrate increased survival lengths when compared with flaps raised on an acute basis. Nutritive blood flow studies performed after skin expansion and elevation show augmented blood flows similar to those seen in conventionally delayed skin flaps. We utilized dermofluorometric analysis to study acute blood flow changes in sequentially, rapidly expanded porcine skin. Four subcutaneous pockets were developed in each of six pigs. The pockets were divided into the following three groups: (1) those with placement of a tissue expander inflated sequentially to 300 mL over four days and then totally deflated on day 6, (2) those with placement of a tissue expander that was not inflated, and (3) those with no tissue expander placed. Measurements were taken immediately before and after tissue expander manipulation in group 1 and daily in groups 2 and 3. Fluorescence was determined at points over and 4, 7, and 10 cm distal to the expander. Blood flow decreased immediately after skin expansion in areas over the tissue expander on days 0 and 1 and returned to baseline levels within 24 hours. Blood flow increased after tissue expander deflation on day 6 but returned to predeflation levels within 24 hours. Capillary blood flow increased over the duration of the study in all three groups. There was no significant difference in blood flow between and among the three groups on day 8, nor was there a significant difference in blood flow between and among sites over and distal to the tissue expander. PMID- 2914090 TI - Pericranial free grafts in the face. AB - The pericranium is a thin connective tissue coating of the neurocranium that can be used as a free graft for selected facial surgery. To assess the potential use of this graft in the face, we describe our experience over a period of 33 months on 34 patients. Eighty-two individual pericranial grafts were used, with an average of 2.4 grafts per patient. The pericranium was used for augmentations, coatings, and suspensions, with the latter two proving to be the most useful. Like other autogenous grafts, the pericranium may eventually undergo some resorption; however, with experience, overcorrection can be planned. The graft is convenient and easy to harvest, with little or no defect at the donor site. With a mean follow-up of 13.6 months, rejection or infection has not been experienced to date. PMID- 2914091 TI - A technique to treat wrestlers' auricular hematoma without interrupting training or competition. AB - Auricular hematoma is a common injury occurring among high school and collegiate wrestlers. Conventional pressure dressings applied over the auricle make it impossible for the athlete to continue to train and to compete, resulting in a high degree of noncompliance. We describe a technique that permits treatment of the hematoma while the athlete continues to train. It involves an incision and drainage followed by the immediate application of a pressure dressing sutured to the auricle. This approach was used to treat 24 auricular hematomas in 19 wrestlers. The analysis demonstrates a low complication rate and documents a rapid return to competition. PMID- 2914092 TI - The effects of allopurinol and superoxide dismutase in a rat model of skin flap necrosis. AB - Oxygen-free radicals have been implicated as mediators of ischemic damage in a number of tissues, including heart, kidney, small intestine, and skin. Superoxide dismutase, a free radical scavenger, and allopurinol, an inhibitor of xanthine oxidase (a catalyst in the formation of superoxide) have been shown separately to decrease ischemic damage to tissue. Sixty-two male Sprague-Dawley rats (220 to 280 g) were divided into five groups: control, superoxide dismutase only, allopurinol only, high-dose combined allopurinol and superoxide dismutase, and low-dose combined allopurinol and superoxide dismutase. An 18-cm2 ventral island skin flap, based on a single inferior epigastric vessel, was raised and replaced. Blood flow was assessed with a perfusion fluorometer immediately after the flap was replaced, and on postoperative days 1 and 3. Gross necrosis was assessed on postoperative day 7. Gross necrosis was reliably reduced in all groups as compared with the control; however, necrosis in any one experimental group was not significantly different from any other experimental group. Necrosis (expressed as a percentage of the area of the random [distal] half of the flap) was as follows for each group: control, 74%; superoxide dismutase, 43%; allopurinol, 43%; high-dose combined, 48%; low-dose combined, 33%. Blood flow, as represented by the dermofluorescence index, was not changed by any of the treatments. Blood flow was also related to the eventual survival or necrosis for any one portion of tissue. All experimental groups survived with significantly less blood flow than the control.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2914093 TI - Intraocular pressure as an index of ocular injury in orbital fractures. AB - An improved method of screening for ocular injuries in patients sustaining orbital fractures is proposed. We performed a retrospective study of 107 patients who sustained orbital fractures. Intraocular pressures were measured on presentation in 17 patients and were found to be elevated on the side of the injury in eight patients, five (63%) of whom had significant ocular injury. No patient with normal intraocular pressure was found to have an ocular injury. In a prospective study, the intraocular pressures of 30 patients sustaining orbital fractures were measured. Twelve patients (40%) had normal (less than 22 mm Hg) and bilaterally symmetric (less than 3 mm Hg difference) intraocular pressures. One (8%) of these patients sustained ocular injury. In contrast, 18 patients (60%) had either an elevated intraocular pressure (greater than 22 mm Hg) or a difference between eyes of greater than or equal to 3 mm Hg. Eleven (61%) of these patients were found to have sustained an ocular injury. We conclude that intraocular hypertension or significant interocular pressure differences should alert the physician to a potential ocular injury. PMID- 2914094 TI - Extension of neuromuscular pedicles and direct nerve implants in the rabbit. AB - Extension of neuromuscular pedicles and direct nerve implants was investigated in ten rabbits. All rabbits underwent facial nerve resection bilaterally. In five rabbits a neuromuscular pedicle, based on the ansa cervicalis nerve, was implanted into the denervated mentalis muscle unilaterally. On the opposite side, reinnervation was attempted using a neuromuscular pedicle with an interposed nerve graft. In the other five rabbits, reinnervation was attempted using a direct nerve implant on one side and a direct nerve implant extended with a nerve graft on the opposite side. Evoked electromyographic muscle tension and histologic studies were used to evaluate reinnervation. Functional neuromuscular units were consistently produced with neuromuscular pedicles, direct nerve implants, and extended direct nerve implants, while extended neuromuscular pedicles failed to produce detectable reinnervation. PMID- 2914095 TI - Clavicular division technique. A new approach for lengthening the pectoralis flap. AB - Complications associated with using the pectoralis major myocutaneous flap increase significantly when a portion of the paddle is randomized and/or the flap is closed under tension. The clavicular division technique was devised to increase the length of the flap to help alleviate this problem. Thirty pectoralis major muscle flaps were dissected in fresh cadavers, using the clavicular division technique. The length of the flap after transposition was measured and recorded before and after clavicular division. The distance from the sternal notch to the clavicular division point was also recorded. The average gain in length was found to be 2.9 cm, with a range of 0.5 cm to 6.5 cm. The clavicular division technique has been used since in five patients. The increase in length has allowed us to discard some or all of the random portion of the flap. We advocate the use of this procedure on any patient where the surgeon is concerned about the viability of the random portion of the flap and/or when it is felt that the tension on the suture line is excessive. PMID- 2914096 TI - A new cocaine abuse complex. Involvement of nose, septum, palate, and pharynx. AB - A new complex of findings caused by cocaine abuse is presented. The complex consists of nasal collapse, septal perforation, palatal retraction, and pharyngeal wall ulceration. The findings and their causes are described. Pathologic evaluation to ensure that a concomitant disease, such as Wegener's granuloma, malignant reticulosis, autoimmune lesion, or various other destructive diseases, was not present was performed on only one patient. Although three patients presented with the findings caused by cocaine abuse, only one patient consented to the biopsy examinations. This case is presented in detail. PMID- 2914097 TI - Parotitis and facial nerve dysfunction. AB - Paralysis of the facial nerve in association with suppurative parotitis is rare, with only ten previously reported cases. In some situations, inflammation surrounding a benign neoplasm accounted for the observed paralysis. In this article, three new cases of parotitis with associated facial nerve dysfunction are described, none of which was associated with a neoplasm. In one, an occult abscess was present and in another an aggressive necrotizing process was seen. The treatment of this disease should initially be conservative management with high doses of wide-spectrum antibiotics. In the majority of cases, resolution of the facial paralysis should follow. However, persistence of a parotid mass with continued facial palsy mandates surgical exploration to exclude the presence of an underlying neoplasm. PMID- 2914098 TI - Pathologic quiz case 2. Leiomyoma of the nasal vestibule. PMID- 2914099 TI - Diplophonia? PMID- 2914100 TI - Evaluation of single-dose cefazolin prophylaxis for toxic shock syndrome. PMID- 2914101 TI - Intermittent herpes simplex. PMID- 2914102 TI - Preservation of the eye in paranasal sinus cancer surgery. PMID- 2914103 TI - Evaluation of the combination effects of ampicillin or vancomycin combined with streptomycin, gentamicin, tobramycin or netilmicin against enterococci. AB - Seven strains of Streptococcus faecalis, of which two possessed high-level resistance to streptomycin (MIC greater than or equal to 2000 mcg/ml), and two strains of Streptococcus faecium were evaluated with respect to killing-effect and duration of post-antibiotic effect (PAE) of ampicillin and vancomycin in combination with streptomycin, gentamicin, tobramycin and netilmicin. No synergistic combination effects were seen with the two strains highly-resistant to streptomycin or with the two Streptococcus faecium strains to netilmicin and tobramycin. When these strains were excluded, no significant difference in average killing could be detected between the four aminoglycosides. The mean prolongation in recovery period of susceptible strains was significantly longer with combinations of ampicillin and netilmicin or streptomycin as compared with either gentamicin or tobramycin. A similar relationship was seen for combinations of vancomycin with the four aminoglycosides. PMID- 2914104 TI - Phenotypic complexity in Mobiluncus. AB - A total of 74 Mobiluncus strains were collected from various laboratories and examined morphologically, biochemically and serologically. Repeated Gram-staining showed a greater variety of cell morphology than hitherto reported with some strains changing their appearance between long and short. All strains except two were motile. Sixty-five of 74 strains were designated M. curtisii and M. mulieris in contrast to atypical strains. In spite of this several of them reacted aberrantly in one or more tests. Biochemical tests and antigenic characterization by monoclonal antimobiluncus antibodies placed most but not all strains in their species groups. One atypical strain had the cellmorphology and biochemical profile of a M. mulieris but reacted only with anticurtisii antibodies. One M. mulieris had the cellmorphology and biochemical profile of a M. curtisii but reacted with an antimulieris antibody. We conclude that there is a greater variance in Mobiluncus' phenotypic appearance than has so far been appreciated. PMID- 2914105 TI - Susceptibility testing of Danish isolates of Capnocytophaga and CDC group DF-2 bacteria. AB - Twelve Capnocytophaga and seven DF-2 strains were tested for their susceptibility to 14 antimicrobial agents using an agar dilution and an agar diffusion method. Twenty-three other antibiotics were evaluated using the diffusion test only. All strains were fully susceptible to penicillin, ampicillin, cefuroxime, cefotaxime, erythromycin, clindamycin, chloramphenicol, doxycycline, rifamycin and ofloxacin using both methods. Clindamycin, rifamycin and cefotaxime were most active. Using agar dilution some strains were susceptible to gentamicin, but agar diffusion showed total resistance. One Capnocytophaga strain was susceptible and another moderately susceptible to metronidazole, other strains were resistant. The agar diffusion test showed that both Capnocytophaga and DF-2 were resistant to most other aminoglycosides, to fosfomycin, polymyxin and trimethoprim. All strains of both taxa were fully susceptible to piperacillin, cefoxitin, imipenem and fusidic acid and showed different susceptibilities to the other agents. Susceptibility testing by means of agar diffusion using an enriched chocolate agar and 5% CO2 atmosphere could be used to test Capnocytophaga and DF-2 strains and gives sufficient accuracy for routine use, when revised inhibition zone breakpoints are employed. PMID- 2914106 TI - Detection of antibody responses in rabbits hyperimmunized with Campylobacter pylori. Enzyme immunoassay indicates extensive antigenic similarities. AB - Acid glycine extracts from four Campylobacter pylori strains and one GCLO strain were used as antigens in enzyme immunoassay (EIA). Immune responses of rabbits immunized with C. pylori strains, the GCLO-strain and other campylobacter strains were studied. All 14 rabbit antisera against C. pylori reacted with all four C. pylori extracts and there were extensive cross-reactions between these extracts. Antisera against C. jejuni and C. coli strains did not react with a C. pylori extract but reached with the GCLO antigen. Acid glycine extracts proved to be very satisfactory in C. pylori serology and the use of an extract prepared from only one strain instead of a combination of strains seems justified. PMID- 2914107 TI - Influence of prostanoids on gastrointestinal mucosal injury in experimental septic shock. AB - Capillary stasis and mucosal injury in the stomach and small intestine were studied in septic shocked pigs. Septicemia was induced by live E. coli i.v. in 28 animals. Additionally, five animals were infused with Ringer's solution and served as sham controls. The 28 E. coli-infused animals were pretreated with either a cyclooxygenase inhibitor--indomethacin, n = 6, a thromboxane (TxA2) synthetase inhibitor--UK 38,485 alone, n = 6, or combined with a serotonin antagonist--ketanserin, n = 9. Seven E. coli-infused animals were left untreated and served as septic controls. The sham controls were hemodynamically stable and had normal histological findings. All bacteria-infused animals exhibited signs of septic shock with pronounced hemodynamic reactions. Attenuation of the bacteria induced increase in pulmonary arterial blood pressure was found in all pretreated animals but most pronounced in the indomethacin-pretreated group which also showed protection against gastric mucosal injury and capillary stasis. TxA2 inhibited animals had aggravated capillary stasis and mucosal injuries. It is concluded that gastric mucosal damage could be modified by drugs influencing the prostanoid system. The "cytoprotective" effect of prostaglandins seem to be of minor importance for the prevention of the gastro-intestinal mucosal injury seen in some series. PMID- 2914108 TI - A case of granulomatous sialadenitis of the submandibular gland. AB - Granulomatous inflammation of the major salivary glands is very rare and may be due to obstruction. Little attention has been paid to this condition. The reaction is caused by extravasation of mucus, as seen in the common mucocele of the minor salivary glands. A case of granulomatous inflammation of the submandibular gland caused by obstruction is presented. The etiology of granulomatous sialadenitis is reviewed. PMID- 2914109 TI - Cell association of HIV in AIDS-related encephalopathy and dementia. AB - The presence of HIV gag and env proteins (HIV Ag) and virus replicating cells was studied by immunohistochemistry and in situ hybridization, respectively, in brain specimens from five HIV infected patients. HIV antigens were detected in 3 of 5 brains in micronodular areas characterized by increased cellularity and the presence of multinuclear giant cells. By double immunostaining, HIV Ag positive cells were shown to express markers common to macrophages and microglia i.e. Leu M5+, My4+, HLA-Dr+, RCA-1+, and to a lesser extent CD4+ (Leu3+). Another macrophage specific marker, KiM6, was found only on HIV+ cells in HIV infected specimens and not in uninfected, control brains. Medium-sized, virus replicating cells were found exclusively in micronodular areas, but in much smaller quantities than HIV Ag+ cells. Our observations provide further evidence to support the hypothesis that macrophages play an important role in CNS infection by HIV and additionally support the concept that reactive microglial originate from activated macrophages infiltrating the brain. Both direct effects of viral components and cell mediated reactions can be implicated from our findings as mechanisms involved in the pathogenesis of the CNS lesions. PMID- 2914110 TI - Evaluation of a rapid test for detection of antibodies against human immunodeficiency virus (HIV). AB - A new test for rapid detection of HIV antibodies (HIVCHEK) was evaluated. A total of 107 sera were examined. Of these, 60 were from healthy blood donors and the rest from a serum panel containing HIV positives and samples with false positive reactions in ELISA and unspecific bands in the western blot (WB). There was close agreement (100%) between the methods. The specificity of the HIVCHEK was 100% in this study. The sensitivity was acceptably high based on testing of consecutive serum samples from two seroconversion patients. The test was rapid and easy to perform, and no extra equipment was needed. PMID- 2914111 TI - Repeated computed tomography in lacunar infarcts of the brain. AB - This prospective and consecutive study of 74 patients with completed stroke elucidates occurrence, localization and evolution of lacunar infarcts on repeated CT examinations. Twenty patients had large infarcts (diameter greater than 3 cm), 25 medium-sized infarcts (diameter greater than or equal to 1.5 cm - less than or equal to 3 cm), and 16 had lacunar infarcts (diameter less than 1.5 cm). In 13 patients no infarct was seen. The lacunar infarcts were characterized by delayed appearance on CT, low incidence of fog effect, and infrequent presence of contrast enhancement. In 9 of the 16 patients (56%) the lacunar infarct could be identified on the first CT, performed approximately 3 days after the stroke. In 2 patients the infarct was first revealed on the second (2 weeks post stroke) and in 5 on the third CT (6 months post stroke). The delayed appearance might be due to a partial volume effect. Early development of fog effect may also be considered. As contrast enhancement was observed in only 8 per cent of the patients with lacunar infarcts on CT, and in 70 per cent of the entire group of patients in our series with ischemic infarcts, contrast enhancement seemed to be a function of lesion size. PMID- 2914112 TI - Computed tomography in massive pulmonary embolism. AB - The usefulness of computed tomography (CT) for the diagnosis of pulmonary embolism (PE) was demonstrated in two cases. Employing dynamic, contrast-enhanced CT, both direct and indirect signs of PE may be rapidly and conveniently demonstrated. Possible contraindications for therapy may be diagnosed simultaneously and follow-up examinations after therapy may be readily performed. The method serves as a good complement when PE must be verified before treatment with potent agents. PMID- 2914114 TI - Computed tomography of ano-rectal anomalies. Correlation between radiologic findings and clinical evaluation of faecal incontinence. AB - Computed tomography (CT) was performed in 9 patients with faecal incontinence more than 8 years after rectoplasty for high imperforate anus. The radiologic findings were correlated with the clinical evaluation of faecal incontinence. No statistically significant correlation was found between function and anatomic findings as demonstrated by CT. Thus, although CT demonstrates the post-operative anatomy in a detailed way, the information does not seem to be directly applicable when selecting the type of reoperation for faecal incontinence. PMID- 2914113 TI - Esophageal motor function evaluated by scintigraphy, video-radiography and manometry in diabetic patients. AB - Prolonged esophageal scintigraphic transit time is frequent in diabetic patients and is related to autonomic neuropathy. In this study, esophageal scintigraphic transit time was correlated to esophageal motor function as evaluated by video radiography and manometry in 13 diabetic patients. An abnormal scintigraphic transit time (greater than 15 s) occurred in 6 patients. All patients with abnormal transit time showed abnormal results at video-radiography (n = 4) and/or manometry (n = 5), which were observed in only 2 of 7 patients with normal transit time (both with abnormal video-radiography and manometry). A prolonged scintigraphic transit appears reliable as an indicator of disturbed esophageal smooth muscle function since it is well correlated with abnormalities shown by a combination of video-radiography and manometry. PMID- 2914115 TI - MR-cholangiography with a double contrast technique. AB - The combination of superparamagnetic particles (SPP) as a 'negative' contrast agent for the liver parenchyma and Cr-HIDA as a 'positive' one for the bile ducts was tested in dogs. The maximum effect of SPP was present about 30 minutes after injection with a reduction of the image intensity of the liver close to the background noise level at the highest dosages. This effect lasted for about 4 to 5 hours and it had disappeared after 24 hours. Before any contrast administration or after Cr-HIDA the bile ducts were not discernible, but a high signal in the gallbladder was present 15 to 30 minutes after injection of Cr-HIDA. After SPP the wider bile ducts were discernible because of the lowering of the signal intensity in the liver. When SPP were followed by Cr-HIDA, the bile had a higher signal intensity, and even tiny bile ducts were visible. After cholecystokinin visualization of the choledochus duct was achieved as well as contrast filling of the duodenum. The blood, urine, and liver function tests were found normal during the experiments. The combination of superparamagnetic particles and Cr-HIDA seems to be a promising method for MR-cholangiography. An evaluation of the anatomic structures of the liver should be possible with this method in different pathologies. PMID- 2914116 TI - Demonstration of splenic and portal veins at routine celiac angiography. A clinical investigation of metrizoate and ioxaglate. AB - The demonstration of splenic and portal veins during routine celiac angiography was prospectively investigated and blindly scored in 25 patients. Two identical angiographic series were performed with randomized intraindividual injections of either metrizoate 280 mg I/ml and ioxaglate 280 mg I/ml or metrizoate 370 mg I/ml and ioxaglate 320 mg I/ml. The splenic and portal veins were significantly better demonstrated when ioxaglate 280 mg I/ml was used, compared with metrizoate 280 mg/ml. No significant difference was found between metrizoate 370 mg I/ml and ioxaglate 320 mg I/ml. Ioxaglate and metrizoate adequately demonstrated the splenic veins but ioxaglate did so at a lower iodine concentration. A slower transcapillary diffusion rate combined with a lower osmolality of ioxaglate compared with metriozate is considered the major explanation for the better demonstration of the veins. PMID- 2914117 TI - Absorbed dose resulting from a specially designed computed tomography technique for examination of the urinary bladder. AB - The absorbed spatial dose distribution resulting from a specially designed CT protocol for examination of the urinary bladder has been investigated with TLD rods in a body phantom containing tissue equivalent material. The CT examination consisted of scout view and both pre- and postcontrast scan series with 5 mm slice thickness and 5 mm unscanned intervals between successive scans. Cross sectional dose distribution for one scan in the plane of the ovaries was measured as well as the dose profile for one scan along a line through the ovary parallel to the axis of rotation. Based on these measurements, the dose resulting from the whole CT examination was calculated, both with contiguous and noncontiguous scans. The ovarian dose was calculated for different positions of the ovaries in relation to the scanned area. The absorbed dose varied between 8.3 mGy and 9.7 mGy with the actual technique used. When contiguous scans with the same thickness were taken, the ovarian dose increased with a factor from 1.7 to 1.9. The dose resulting from the CT protocol of the urinary bladder was of the same magnitude as absorbed dose resulting from urography. When the diagnostic gain from a precise definition of tumor extent was taken into account, the dose resulting from the CT protocol was judged acceptable. PMID- 2914118 TI - Roentgenologic assessment of spondylolisthesis. II. An evaluation of progression. AB - Different degrees of artificial L5-S1 spondylolisthesis were created using a lumbar specimen. Lateral radiographs were obtained of each, with the specimen tilted and/or rotated. The true spondylolisthesis was determined stereophotogrammetrically. The slip, measured on the radiographs, was calculated according to two methods modified from Boxall et coll. No significant difference in accuracy was found between these two methods. The difference in calculated slip between examinations needs to be at least 20 per cent of the sagittal length of L5 to be regarded as a true progression. A true progress of slip of less than 20 per cent is difficult to detect with statistical certainty. PMID- 2914119 TI - Evaluation of three methods for measurement of femoral neck anteversion. Femoral neck anteversion, definition, measuring methods and errors. AB - A variety of methods exist for determining femoral neck anteversion. There is, however, no consistent definition or reference method by which the correctness of the measurements can be determined. In this report the precision of a specific definition of femoral neck anteversion is estimated by means of a reference method. Three different radiologic measuring methods based on fundamentally different principles are evaluated by comparison with this reference. It is concluded that: 1) The Dunlap/Rippstein method can be recommended as the standard method. 2) Computed tomography may have substantial sources of error. 3) Methods based on arbitrary projections have poor precision. PMID- 2914120 TI - Multicystic acoustic neuroma. Case report and differential diagnosis. AB - A rare case of a multicystic acoustic neuroma is reported. At computed tomography (CT) and magnetic resonance imaging (MRI) the tumor was found to cause hydrocephalus, and displacement of the brainstem. The multicystic character was revealed on CT, while MRI only showed the mass lesion and the common signal intensities for an acoustic neuroma. The differential diagnosis of a multicystic lesion in the cerebellopontine angle is discussed. PMID- 2914121 TI - Assessment of tibial torsion employing fluoroscopy, computed tomography and the cryosectioning technique. AB - Accurate assessment of tibial torsion, particularly the rotational deformity of a stabilized tibial fracture, demands precise anatomic landmarks at the proximal and distal measuring sites of the tibia. A fluoroscopic method has been proposed, utilizing the orientation of the femoral condyles and the medial malleolus to constitute two lines of reference. The relevance of using these structures for the assessment was studied while employing fluoroscopy, computed tomography, and the cryosectioning technique in 10 necropsy specimens of the human tibia. In all specimens the lines of reference were determined by each method and the tibial torsion was measured as the angle between the lines. The medial malleolus and the femoral condyles were found to present reliable anatomic landmarks for determination of the lines of reference in all employed techniques. The maximum difference between results obtained with different methods in a given specimen was 5.4 degrees. The average difference between results with two techniques and two observers varied from 1.0 to 1.5 degrees. The reproducibility of the fluoroscopic method, described by the estimated standard error of a single determination, was 1.3 degree. PMID- 2914122 TI - Pharmacokinetics of three contrast media in experimental pancreatography. AB - Diatrizoate, iohexol and ioxaglate were compared in experimental pancreatography in piglets. Outflow of contrast medium (CM) through the pancreatic papilla was permitted (n = 14) or impaired (n = 17) during examination. The CM concentrations were measured in portal and systemic plasma and in lymph to study the absorption of CM. Absorption of diatrizoate and iohexol was similar in both types of experiment, but radiographically, diatrizoate escaped significantly earlier from the pancreatic duct when outflow was permitted (p less than 0.01), suggesting that the CM was absorbed mainly during injection. Ioxaglate concentrations rose more slowly in systemic plasma and lymph, and fell more slowly in the portal plasma than those of diatrizoate and iohexol, which suggests that ioxaglate was absorbed over a longer period. When outflow was impaired, ioxaglate concentrations remained on a lower level, indicating less penetration in the pancreatic parenchyma. CM absorption varied markedly within each group, suggesting that variations in intraductal pressure and flow are more important in absorption than the type of CM used. PMID- 2914123 TI - Urinary excretion of iohexol after intestinal administration in rats with bowel ischaemia. The effects of mesenteric arterial and/or venous occlusion. AB - Serum and urinary levels of iohexol (Omnipaque) were evaluated in 28 rats after instillation of 1.5 ml of contrast medium directly into closed small bowel segments of equal length. Ten rats had a ligature applied to the anterior mesenteric artery and vein via laparotomy, 10 animals had a ligature of the vein only and 8 had no vascular occlusion (operated controls). In addition, 3 rats (non-operated controls, normals) were gavaged with a similar volume of the same contrast medium. Radiographs were obtained every hour. Biopsy samples and blood and urine tests were taken at the end of the 4-hour observation period. On radiographs, a marked increase of urinary bladder opacity was observed after 2 to 4 hours in the rats with both vessels tied. Correspondingly high iodine levels were measured in the urine and serum at 4 hours by x-ray fluorescence analysis. Urinary levels were 27 times and serum levels 8 times that of operated controls, respectively, and 81 and 25 times that of normals. Venous occlusion affected the bladder opacity to a lesser extent, giving urinary iodine levels 12 times and serum levels twice that of normal controls. Neither urinary nor serum iodine levels were significantly different from the operated controls. The operated controls had urinary concentrations of contrast medium 3 times that of the gavaged normal controls, but a barely visible urinary bladder on radiographs. Measuring iodine levels in serum or urine may be helpful in the evaluation of the degree of mucosal injury induced by intestinal ischaemia. PMID- 2914124 TI - Granulocyte chemotaxis. Chemoattractive properties of a synthetic tripeptide are inhibited by radiographic contrast media. AB - The under agarose method for evaluation of leucocyte chemotaxis was used to investigate the effect of radiographic contrast media (CM) on granulocyte locomotion. The CM tested had no chemoattractive properties. CM inhibited N-fmlp, a synthetic formylated Met-tripeptide, which is a strong chemotactic agent and an analogue to chemotatic peptides produced by bacteria. The inhibition of N-fmlp was most pronounced for diatrizoate. Equiosmolal saline was not so inhibitive. Therefore, some part of the inhibition was caused by factor(s) other than hyperosmolality inherent in the CM solution. PMID- 2914125 TI - Characterization of Rose Bengal binding to sinusoidal and bile canalicular plasma membrane from rat liver. AB - The binding of Rose bengal, a model organic anion, to sinusoidal and bile canalicular membrane fractions isolated from rat liver was compared. The fluorescence change of Rose bengal after being bound to liver plasma membranes was utilized for measuring the binding. The dissociation constants (Kd = 0.1-0.12 microM) and the binding capacities (n = 11-15 nmol/mg protein) for Rose bengal are comparable between the two membrane fractions, although the n value for sinusoidal membrane is somewhat larger than that for bile canalicular membrane. The Rose bengal binding to both membrane fractions was inhibited by various organic anions at relatively low concentrations, i.e., the half-inhibition concentrations (IC50) for Indocyanine green, sulfobromophthalein, Bromophenol blue and 1-anilino-8-naphthalene sulfonate were 0.1, 100, 1.5-2.5 and 100 microM, respectively, while taurocholate did not inhibit the Rose bengal binding to either membrane fraction at these low concentration ranges. The type of inhibition of sulfobromophthalein and Indocyanine green for Rose bengal binding is different between the two membrane domains. That is, in sinusoidal and bile canalicular membrane fractions, these organic anions exhibit mixed-type and competitive-type inhibition, respectively. It was suggested that the fluorescence method using Rose bengal may provide a simple method for detecting the specific organic anion binding protein(s) in the liver plasma membrane. PMID- 2914126 TI - Influence of plasmalogen deficiency on membrane fluidity of human skin fibroblasts: a fluorescence anisotropy study. AB - The influence of plasmalogen deficiency on membrane lipid mobility was determined by measuring fluorescence anisotropy of trimethylammoniumdiphenylhexatriene (TMA DPH) and diphenylhexatrienylpropanoylhydrazylstachyose (glyco-DPH) inserted in the plasma membranes of human skin fibroblasts deficient in plasmalogens. The cells used were from patients affected with cerebrohepatorenal (Zellweger) syndrome (CHRS) or rhizomelic chondrodysplasia punctata. Their plasmalogen content (0-5% of total phospholipid) is significantly reduced compared with that of control cells from healthy donors (13-15% of total phospholipid) or of CHRS fibroblasts supplemented with the plasmalogen precursor, hexadecylglycerol. Plasmalogen-deficient cells consistently showed lower fluorescence anisotropies of membrane-bound DPH fluorophores corresponding to higher membrane lipid mobilities as compared to controls. However, very similar lipid mobilities were found for sonicated aqueous dispersions of phospholipids extracted either from CHRS or control cells. Therefore, the differences observed with living cells are not due to differences in the overall physical properties of the membrane lipid constituents. Other phenomena such as lipid asymmetry and/or plasmalogen-protein interactions may be responsible for the effects observed in the biomembranes. PMID- 2914127 TI - Quinine inhibits multiple Na+ and K+ transport mechanisms in Ehrlich ascites tumor cells. AB - The interaction of quinine with K+ and Na+ transport mechanisms has been investigated in Ehrlich ascites tumor cells. Quinine affects both Ca2+-dependent K+ channel and total K+ influx. Activation of Ca+-dependent K+ channels by propranolol is abolished by quinine (1 mM). In addition, quinine inhibits the ouabain-sensitive component of K+ influx with an apparent Ki of 0.32 +/- 0.02 mM and the furosemide-sensitive component with a Ki of 0.24 +/- 0.01 mM. Furthermore, a significant fraction (52%) of Na+ influx is inhibited by quinine. The same component is sensitive to amiloride, suggesting that it represents Na+/H+ antiport. Concomitant with the inhibition of K+ and Na+ transport, quinine stimulates ATP hydrolysis by 57%. The results suggest that quinine exerts broad, nonspecific effects on cellular mechanisms which serve to regulate cation transport in Ehrlich cells. PMID- 2914128 TI - The characterisation of liposomes with covalently attached proteins. AB - The problem of characterising liposomes with covalently attached proteins has been analysed theoretically in terms of a normal weight distribution of liposome diameters. The polydispersity of protein conjugation is considered in terms of the width (standard deviation) of the liposome size distribution. It is shown that the weight-average number of proteins per liposome is a convenient parameter to use to define the protein content of proteoliposomes. Two types of proteoliposome have been prepared (small unilamellar vesicles and reverse phase evaporation vesicles) in which wheat germ agglutinin is covalently coupled to the liposomal surface. The liposomes cover a range of weight average diameter from 65 to 240 nm and of polydispersity (weight to number average diameter (dw/dn) from 2.6 to 11.4. The liposomes have been characterised by chemical analysis and photon correlation spectroscopy and the results are discussed in terms of the theoretical consequences of an equivalent normal weight distribution of diameters. PMID- 2914129 TI - Modulation of the Ca2+- or Pb2+-activated K+-selective channels in human red cells. II. Parallelisms to modulation of the activity of a membrane-bound oxidoreductase. AB - Modulation of Ca2+-activable K+ permeability was compared with modulation of a membrane-bound oxidoreductase activity in human erythrocytes. Changes in the K+ permeability were monitored by flux measurements and single-channel recordings. The enzyme activity was detected by measuring reduction of ferricyanide. Pb2+, Atebrin and menadione had parallel effects on the channel protein and the enzyme. In contrast, propranolol stimulates K+ permeability, but is without effect on enzyme activity. The results demonstrate that the K+ channel and the enzyme are distinct membrane proteins but that the enzyme activity may influence channel gating. PMID- 2914130 TI - Characterization of Ca2+-binding proteins from Ehrlich ascites tumor cell cytoplasm and their binding to membranes. AB - A set of proteins in the 33-37 kDa range have been isolated from the cytoplasm of the Ehrlich ascites tumor cell. The proteins are characterized by their Ca2+ dependent binding to cell membranes. This property has been used for isolation of the proteins by Ca2+-dependent affinity binding to inside-out vesicles of the human red cell membrane. The proteins display Ca2+-binding properties as shown by gel-filtration studies. The Ca2+-dependent binding of the 33 and 34 kDa proteins to red cell membranes was studied after labelling of the proteins with tritium by reductive methylation. The average number of Ca2+ bound per protein molecule was 4.8 with a Kd of 3.4.10(-4) M Ca2+. The proteins are distinct from most other Ca2+-binding proteins of comparable molecular weights by not incorporating phosphate. PMID- 2914131 TI - Preparation of hemoglobin-containing liposomes using octyl glucoside and octyltetraoxyethylene. AB - Hemoglobin (Hb) was encapsulated in phosphatidylcholine vesicles by removal of the detergent n-octyl beta-D-glucoside (OG) or n-octyltetraoxyethylene (C8E4) out of mixed detergent-lipid micelles in Hb solution. Three types of apparatus were used for dialysis. Dialysis buffer flow rates, the surface area of the dialysis membranes, and detergent-lipid interactions determined the rate of dialysis, which influenced liposome size and lamellarity. Slow dialysis led to the formation of multilamellar liposomes, at increased dialysis rates Hb liposomes became smaller and unilamellar. Hb was enclosed at highest concentrations in larger liposomes, which included the negatively charged lipid phosphatidylserine or phosphatidic acid as a membrane component. Co-encapsulation of the allosteric factor inositol hexaphosphate led to oxygen dissociation curve values almost identical to those of whole blood. The oxygen-release capacity of Hb liposome suspensions in the physiological partial pressure range was comparable to whole blood. Storage of Hb liposomes for 2 months leaves oxygen-carrying characteristics virtually unchanged, with met-Hb levels increasing to only 11% of total Hb. Preparation of Hb liposomes by dialysis of octyl glucoside or C8E4 is a mild and efficient method for encapsulation of Hb. Since these Hb liposomes can be produced in scale-up batch sizes, they are a candidate for use as an oxygen carrying blood surrogate. PMID- 2914132 TI - Sodium-calcium exchange in transverse tubules isolated from frog skeletal muscle. AB - Transverse tubule vesicles isolated from frog skeletal muscle display sodium calcium exchange activity, which was characterized measuring 45Ca influx in vesicles incubated with sodium. The initial rates of exchange varied as a function of the membrane diffusion potentials imposed across the membrane vesicles, increasing with positive intravesicular potentials according to an electrogenic exchange with a stoichiometry greater than 2 sodium ions per calcium ion transported. The exchange activity was a saturable function of extravesicular free calcium, with an apparent K0.5 value of 3 microM and maximal rates of exchange ranging from 3 to 5 nmol/mg protein per 5 s. The exchange rate increased when intravesicular sodium concentration was increased; saturation was approached when vesicles were incubated with concentrations of 160 mM sodium. The isolated transverse tubule vesicles, which are sealed with the cytoplasmic side out, had a luminal content of 112 +/- 39 nmol calcium per mg protein. In the absence of sodium, the exchanger carried out electroneutral calcium-calcium exchange, which was stimulated by increasing potassium concentrations in the intravesicular side. Calcium-calcium exchange showed an extravesicular calcium dependence similar to the calcium dependence of the sodium-calcium exchange, with an apparent K0.5 of 6 microM. Sodium-calcium and calcium-calcium exchange were both inhibited by amiloride. The sodium-calcium exchange system operated both in the forward and in the reverse mode; sodium, as well as calcium, induced calcium efflux from 45Ca loaded vesicles. This system may play an important role in decreasing the intracellular calcium concentration in skeletal muscle following electrical stimulation. PMID- 2914133 TI - Curvature and composition-dependent lipid asymmetry in phosphatidylcholine vesicles containing phosphatidylethanolamine and gangliosides. AB - The effect of curvature on transbilayer lipid asymmetry in vesicles is investigated using vesicles of different sizes (30-140 nm) prepared by sonication and polycarbonate filter extrusion techniques. The transbilayer distributions of phosphatidylethanolamine and gangliosides are measured using 2,4,6 trinitrobenzenesulphonic acid and Clostridium perfringens neuraminidase as non penetrating probes, respectively. The distribution of phosphatidylethanolamine in a phosphatidylcholine/phosphatidylethanolamine (4:1, molar ratio) system is more or less symmetric and curvature seems to have little effect. However, the distribution of gangliosides in a phosphatidylcholine/ganglioside (10:1, molar ratio) system is asymmetric in favour of the outer layer in smaller vesicles, the asymmetry disappearing as the degree of curvature decreases. In a phosphatidylcholine/phosphatidylethanolamine/ganglioside (8:2:1, molar ratio) system, both phosphatidylethanolamine and gangliosides distribute asymmetrically, indicating a composition-dependent asymmetric distribution of phosphatidylethanolamine. In this system asymmetry also increases with increasing curvature. The asymmetric distribution of gangliosides in vesicles of low curvature may be due to their long headgroup and larger headgroup surface area in accordance with the theoretical predictions of Israelachvili et al. (Biochim. Biophys. Acta 470 (1977) 185-201). PMID- 2914134 TI - Interaction of trichorzianines A and B with model membranes and with the amoeba Dictyostelium. AB - Trichorzianines A (TA) and B (TB) are microheterogeneous mixtures of antibiotic nonadecapeptides of the peptaibol class which interact with lipidic membranes and modify their permeability properties. The TB differ from the TA by replacement of the Gln-18 by a Glu, giving rise to a C-terminal negative charge at neutral pH. The role of this charge on the trichorzianine-lipid interaction was investigated with model membranes by fluorescence spectroscopy and the results were correlated with the biological activity toward the amoeba Dictyostelium discoideum. The interaction of the acidic trichorzianine TB IIIc (Glu-18) with phospholipid bilayers and the subsequent induced permeability were weaker than that exhibited by the uncharged TA IIIc (Gln-18) and MeTB IIIc (TB IIIc monomethyl ester). The unfavourable effect of the negative charge in TB IIIc was strongly enhanced by incorporation of cholesterol in the bilayer. Similarly, TA IIIc as well as MeTB IIIc induced growth inhibition and lysis of the amoeba Dictyostelium at four times lower concentrations than TB IIIc. The results suggested that the interaction of trichorzianines with the phospholipid bilayer and the subsequent modifications of permeability were involved in the inhibitory properties and cell lysis induced by trichorzianines toward Dictyostelium. PMID- 2914135 TI - Temperature-sensitive release of adriamycin, an amphiphilic antitumor agent, from dipalmitoylphosphatidylcholine-cholesterol liposomes. AB - Drugs for temperature-sensitive liposomes have been limited to the hydrophilic drugs, such as methotrexate and cis-dichlorodiammineplatinum, with a low affinity for the lipid bilayer. It was, however, of importance to investigate whether the concept of temperature-sensitive liposomes can be extended to amphiphilic or lipophilic compounds, because some useful drugs are amphiphilic or lipophilic. In this study we tried to use adriamycin, an amphiphilic antitumor agent, as a drug for temperature-sensitive liposomes. In the absence of serum, the liposomes prepared from dipalmitoylphosphatidylcholine released adriamycin in a temperature sensitive manner, i.e., they retained the major portion of entrapped adriamycin at a lower temperature 32 degrees C, and released around 70% of the drug at 42 degrees C, a temperature higher than the phase-transition temperature of the phospholipid. However, when serum was present, the liposomes were leaky even at 32 degrees C. To raise the stability of the liposomes, we included various mol% of cholesterol in the liposomal membrane and examined temperature sensitivity and stability of the liposomes in the presence of serum. Our results indicated that the liposomes including 20 mol% cholesterol were considerably stable and exhibited the maximal temperature-sensitive release of adriamycin in the presence of serum. PMID- 2914137 TI - Wave-guide spectroscopy on planar lipid bilayers doped with hydrophobic ions. AB - Wave-guide spectroscopy exploits the light pipe properties of planar lipid bilayers by propagating a light wave along the plane of the bilayer. Applying this technique to the optical absorption of chromophore in the membrane, results in an enhanced sensitivity when compared to normal incidence spectroscopy. This gain factor is of the order of 100 per mm optical path along the bilayer, thus transforming the weak absorbances in lipid membranes into easily measurable quantities. Wave-guide spectroscopy has been used to measure the adsorption isotherm of hydrophobic dipicrylamine ions in a phosphatidylcholine membrane. The adsorption isotherm is linear for low aqueous concentrations, in the micromolar range however, it changes into a sublinear dependence. The addition of an inert alkali salt to the electrolyte favours the adsorption of hydrophobic ions. Current saturation is observed with the transition to the sublinear isotherm. When using the time constant for current relaxation as an indicator of changes in the magnitude of the surface potential, it does not seem to vary with the additional dipicrylamine which adsorbs in the presence of high concentrations of alkali salt in the electrolyte. A compensation of hydrophobic charge by the alkali ions from the inert electrolyte is proposed. PMID- 2914136 TI - Human platelets mediate iron release from transferrin by adenine nucleotide dependent and -independent mechanisms. AB - We assessed the ability of platelet sonicates and mediators secreted by unstimulated and thrombin-stimulated platelets to facilitate the release of iron from transferrin. Platelet sonicates and platelet conditioned media potentiated the release of iron from transferrin. The rate of release of iron was dependent on the pH of the reaction and amount of platelet sample added. Conditioned media from thrombin-stimulated platelets was more effective in mediating the release of iron from transferrin than was conditioned media from unstimulated cells. The rate of iron released from transferrin following addition of ATP and ADP in amounts equivalent to that present in platelet conditioned media was significantly less than the rate of iron released following the addition of conditioned media from platelets. Depletion of ATP and ADP in platelet conditioned media by incubation with apyrase only partially inhibited their ability to enhance the rate of iron release from transferrin. These observations indicate that platelets enhance the release of iron from transferrin by adenine nucleotide-dependent and -independent mechanisms. These observations are consistent with the hypothesis that platelets promote oxidant-induced tissue injury at sights of inflammation secondary to their ability to enhance the local release of iron from transferrin. PMID- 2914138 TI - Topography of surface-exposed amino acids in the membrane protein bacteriorhodopsin determined by proteolysis and micro-sequencing. AB - The topography of membrane-surface-exposed amino acids in the light-driven proton pump bacteriorhodopsin (BR) was studied. By limited proteolysis of purple membrane with papain or proteinase K, domains were cleaved, separated by SDS PAGE, and electroblotted onto polyvinylidene difluoride (PVDF) membranes. Fragments transferred were sequenced in a gas-phase sequencer. Papain cleavage sites at Gly-65, Gly-72, and Gly-231, previously only deduced from the apparent molecular weight of the digestion fragments, could be confirmed by N-terminal micro-sequencing. By proteinase K, cleavage occurred at Gln-3, Phe-71, Gly-72, Tyr-131, Tyr-133, and Ser-226, i.e., in regions previously suggested to be surface-exposed. Additionally, proteinase-K cleavage sites at Thr-121 and Leu-127 were identified, which are sites predicted to be in the alpha-helical membrane spanning segment D. Our results, especially that the amino acids Gly-122 to Tyr 133 are protruding into the aqueous environment, place new constraints on the amino-acid folding of BR across the purple membrane. The validity of theoretical prediction methods of the secondary structure and polypeptide folding for membrane proteins is challenged. The results on BR show that micro-sequencing of peptides separated by SDS-PAGE and blotted to PVDF can be successfully applied to the study of membrane proteins. PMID- 2914139 TI - Aminophospholipid translocase in the plasma membrane of Friend erythroleukemic cells can induce an asymmetric topology for phosphatidylserine but not for phosphatidylethanolamine. AB - The ATP-dependent translocation of phospholipids in the plasma membrane of intact Friend erythroleukemic cells (FELCs) was studied in comparison with that in the membrane of mature murine erythrocytes. This was done by following the fate of radiolabeled phospholipid molecules, previously inserted into the outer monolayer of the plasma membranes by using a non-specific lipid transfer protein. The transbilayer equilibration of these probe molecules was monitored by treating the cells--under essentially non-lytic conditions--with phospholipases A2 of different origin. Rapid reorientations of the newly introduced aminophospholipids in favour of the inner membrane leaflet were observed in fresh mouse erythrocytes; the inward translocation of phosphatidylcholine (PC) in this membrane proceeded relatively slow. In FELCs, on the other hand, all three glycerophospholipids equilibrated over both halves of the plasma membrane very rapidly, i.e. within 1 h; nevertheless, an asymmetric distribution in favour of the inner monolayer was only observed for phosphatidylserine (PS). Lowering the ATP-level in the FELCs caused a reduction in the rate of inward translocation of both aminophospholipids, but not of that of PC, indicating that this translocation of PS and phosphatidylethanolamine (PE) is clearly ATP-dependent. Hence, the situation in the plasma membrane of the FELC is rather unique in a sense that, though an ATP-dependent translocase is present and active both for PS and PE, its activity results in an asymmetric distribution of PS, but not of PE. This remarkable situation might be the consequence of the fact that, in contrast to the mature red cell, this precursor cell still lacks a complete membrane skeletal network. PMID- 2914140 TI - Anion transport through the contraluminal cell membrane of renal proximal tubule. The influence of hydrophobicity and molecular charge distribution on the inhibitory activity of organic anions. AB - Three different mechanisms of anion transport have been identified for the contraluminal membrane in the proximal tubule of the rat kidney. These mechanisms are specific for the transport of sulfate, dicarboxylate and p-aminohippurate anions. Sulfate transport is inhibited by bivalent organic anions with a distance between the charges of less than 7 A. The sulfate system acts in two modes: in a planar mode for anions with flat charged residues such as COO- and a charge separation of 3-4 A or in a bulky mode for groups such as SO3H- and a charge separation of 4-7 A. Monovalent anions can be accepted if there is a hydrophobic core next to the negative charges. Dicarboxylate transport is inhibited exclusively by anions with two charge centers located within 5 to 9 A, one of those possibly being a partial charge of -0.5 elementary charges. p Aminohippurate transport is inhibited by monovalent anions, if these have a hydrophobic domain with a minimal length of about 4 A. Bivalent anions inhibit, if they have a charge distance of 6-10 A; both charges can be partial charges of about -0.5 elementary charges. Longer bivalent anions can be effective provided they have a sufficiently large hydrophobic domain. For the sulfate and p aminohippurate systems it is found that anions with high acidity yield good inhibition. The overlapping specificities of the three systems with respect to charge distance and hydrophobicity allow them to accept a large variety of organic anions. PMID- 2914141 TI - Electric pulse induced membrane permeabilization. Spatial orientation and kinetics of solute efflux in freely suspended and dielectrophoretically aligned plant mesophyll protoplasts. AB - Asymmetric breakdown (occurring in only one hemisphere of the cell) was induced in freely suspended and dielectrophoretically aligned vacuole-containing or evacuolated plant protoplasts as well as in isolated vacuoles. In suspended cells breakdown was restricted to the hemisphere facing the anode and in isolated vacuoles to the opposite hemisphere. This difference in the orientation of the asymmetric breakdown can be explained by the opposite direction of the intrinsic membrane potentials of isolated vacuoles and of cells on which the generated potential difference is superimposed. The ensuing permeabilization of the membrane was microscopically monitored by dye uptake and by release of chloroplasts and of cytoplasmic and/or vacuolar solutes. The asymmetric release of intracellular substances (organic acids and/or amino acids) was detected by accumulation of chemotactic bacteria (Pseudomonas aeruginosa) close to the permeabilised membrane area of the cells or vacuoles. Maximum bacteria accumulation required about 5 min and subsequently disappeared after a further 20 min presumably because of the restoration of the original membrane impermeability. With vacuoles retention of the accumulated bacteria was shorter indicating that the resealing process of the tonoplast membrane was faster than that of the plasmalemma. From the kinetics of bacteria accumulation and retention it is therefore possible to deduce information about the life-span and the resealing properties of electropermeabilized membrane areas on the single-cell level. Symmetric breakdown in both hemispheres of the cells could be achieved by electric field-mediated cell rotation of about 180 degrees between two pulses of the same polarity or by application of two pulses of alternating polarity. In dielectrophoretically aligned protoplasts of comparable diameter, breakdown occurred in both hemispheres, even though the breakdown was still asymmetric. It could be demonstrated by the uptake of the vital dye neutral red that the size of the membrane area which was permeabilized was much larger in that hemisphere oriented to the anode than in the other one. The relevance of these observations for further improvement of electroinjection of macromolecules and of electrofusion is discussed. In particular, it is pointed out that positioning of differently sized cells in electric field-mediated hybridisation and the polarity of the breakdown pulse is of great importance with respect to hybrid yield. PMID- 2914142 TI - Adsorption of the cationic antitumoral drug celiptium to phosphatidylglycerol in membrane model systems. Effect on membrane electrical properties. AB - The binding of the cationic antitumoral drug Celiptium to the anionic phospholipid phosphatidylglycerol was studied by measuring surface potentials and surface pressures in monolayers, and by determination of electrophoretic mobility on liposomes. Surface potential and zeta potential data were interpreted in terms of the Gouy-Chapman-Stern theory of the diffuse electrical double layer. A unique drug-to-lipid adsorption constant KaD, could not be calculated. KaD was observed to increase rapidly from 10(4) M-1 to 10(6) M-1 with an increase in drug concentration from 5 x 10(-7) M to 7 x 10(-6) M. This was accompanied by a marked decrease (in absolute value) in the corresponding electrophoretic mobilities which, from negative at low drug concentrations, became positive at drug concentrations of 10(-5) M and above. This indicates that the drug-to-lipid binding cannot be accounted for by a simple Langmuir adsorption isotherm, but corresponds to a more complex process, probably of a cooperative nature. Comparison of delta V and zeta potential data shows that adsorption of Celiptium to phosphatidylglycerol not only lowers the electrical surface potential, psi 0 (in absolute value) but also markedly reduces the polarization potential, delta Vp. These observations suggest that Celiptium destabilizes the electrical properties of cell plasma membranes. PMID- 2914143 TI - Carrier-mediated transport system for cephalexin in human placental brush-border membrane vesicles. AB - The uptake of cephalosporin antibiotics, cephalexin, was studied with brush border microvillous plasma membrane vesicles prepared and purified from human full-term placental syncytiotrophoblasts. The uptake of cephalexin by the membrane vesicles was not stimulated in the presence of an Na+ gradient from the outside to the inside of the vesicles, whereas alpha-(methylamino)isobutyrate uptake into the vesicles of the same preparation was stimulated by an Na+ gradient. The equilibrium level of cephalexin uptake decreased with increasing osmolarity of the medium, which indicates that cephalexin is transported into the membrane vesicles. When cephalexin concentrations were varied, the initial rate of uptake obeyed Michaelis-Menten kinetics with Km and Vmax values of 2.29 mM and 2.98 nmol/mg of protein per 60 s, respectively. The uptake of cephalexin was inhibited by structural analogues and sulfhydryl modifying reagents. These results indicate the existence of a carrier-mediated transport system for cephalexin in the human placental brush-border membranes. PMID- 2914144 TI - Depth-dependent photolabelling of membrane hydrophobic core with 9-diazofluorene 2-butyric acid. AB - Hydrophobic photoactivable reagents, which readily partition into membranes, have proved very useful for studying membrane hydrophobic core. These reagents have been linked to fatty acids in order to obtain amphipathic photoactivable reagents which label membranes more effectively. By varying the length of these amphipathic reagents, an attempt to label membrane hydrophobic core at different depths can be made. We report here 9-diazofluorene-2-butyric acid as a new photoactivable reagent which labels the single bilayer vesicles prepared from egg phosphatidylcholine. The labelling site on the fatty acyl chains could be traced to be between the carbon atom 4 and 6. The new probe thus labels the membrane at a site which is proximal to what can be predicted from its length and transverse location in membranes. PMID- 2914145 TI - The effects of homologous series of anaesthetics on a resting potassium conductance of the squid giant axon. AB - The effects of n-alkanes (n-pentane to n-octane), n-alkanols (n-pentanol to n undecanol) and two carboxylic esters (methyl pentanoate and methyl octanoate) on the conductance of squid giant axons in a high potassium, zero sodium bathing solution have been examined. Sodium and delayed rectifier potassium channels were as far as possible pharmacologically blocked. A substantial fraction of the measured conductance is attributed to a recently-described, voltage-independent, potassium channel. Anaesthetics block this channel but its sensitivity is markedly different from those of other squid axon ion channels. PMID- 2914146 TI - Monoclonal antibodies against different domains of cellobiohydrolase I and II from Trichoderma reesei. AB - Monoclonal antibodies have been produced against two functionally different domains present in two cellobiohydrolases from Trichoderma reesei (CBH I and CBH II). Four groups of antibodies were obtained, which specifically recognized (Western blotting, ELISA) (a) the core protein within CBH I, (b) the core protein within CBH II, (c) the BA region of CBH I, and (d) the ABB' region of CBH II. No cross-reactivities within these four groups were observed. The antibodies reacted also specifically with proteins of similar size to CBH I and CBH II (SDS-PAGE) from other Trichoderma strains (Western blotting), whereas no reaction was observed with cellulases from other fungal sources. Analysis of culture filtrates of T. reesei QM 9414 harvested at various times of growth on cellulose under buffered conditions (pH 5-6) indicated the presence of only single bands of CBH I and CBH II, even after prolonged cultivation (160 h). Cultivation on cellulose in unbuffered media, however, showed the appearance (Western blotting) of additional lower molecular weight proteins, which reacted with the monoclonal antibodies directed against the cores of CBH I and II, but not with those recognizing the respective BA and ABB' regions. The appearance of these lower molecular weight bands was most pronounced in unbuffered media, supplemented with a 3-fold (w/w) amount of organic nitrogen (peptone). Analysis of some commercial cellulase preparations from T. harzianum revealed the same pattern of lower molecular weight proteins, in contrast to samples from other fungal cellulases. Those samples or preparations, showing a multiple pattern of CBH I and CBH II, exhibited higher activities of an acid proteinase. These results imply that the use of unbuffered, high nitrogen-supplemented culture conditions for production of cellulases may lead to considerable proteolytic modification of the secreted cellobiohydrolases. PMID- 2914147 TI - Conversion of fibrinogen to fibrin induced by preferential release of fibrinopeptide B. AB - Fibrin clot-promoting enzyme preferentially releasing fibrinopeptide B from fibrinogen was isolated from the crude venom of Agkistrodon contortrix and its mode of action was studied in detail. A purification procedure involving affinity chromatographies on immobilized lectin and arginine removed plasmin-like and kallikrein-like activities towards low-molecular-weight chromogenic substrates. Fibrin-promoting enzyme cleaved off only fibrinopeptides A and B from fibrinogen. The initial relative rate of release of fibrinopeptide B/fibrinopeptide A depended strongly on the presence of Ca2+. In the absence of Ca2+ the amount of fibrinopeptides released by fibrin-promoting enzyme at the gel point was greater. Fibrinopeptide B was no longer released before fibrinopeptide A from the non polymerizing N-terminal disulphide knot of fibrinogen. Catalyzed by activated factor XIII, complete gamma-dimer and alpha-polymer formation was observed in fibrin from which only 23% of fibrinopeptide A, but 100% of fibrinopeptide B was released by fibrin-promoting enzyme. gamma-dimer formation markedly preceded alpha-polymer formation. These results strongly imply a similar overall arrangement of monomer molecules in this fibrin when compared with a thrombin induced fibrin in which fibrinopeptide A is released before fibrinopeptide B. These observations support the concept that on fibrinopeptide B release from fibrinogen polymerization sites are exposed which reinforce the sites exposed on the release of fibrinopeptide A. PMID- 2914149 TI - Purification and characterization of a cofactor that controls the oxidative phase of the pentose phosphate cycle in liver and other tissues of rat. AB - We have recently reported the presence, in rat liver, of a cofactor characterized as a protein of Mr 10(5), which cooperates with GSSG to prevent the inhibition of glucose-6-phosphate dehydrogenase by NADPH. The inhibition that this coenzyme also exerts on 6-phosphogluconate dehydrogenase is similarly prevented by a cofactor-GSSG system. The activity of the cofactor increases in the livers of rats fed on carbohydrate-rich diets. Purification of the components in rat liver homogenate by ion-exchange chromatography and preparative polyacrylamide gel electrophoresis showed that the deinhibitory effect on both dehydrogenases is exerted by the same cofactor. The purified cofactor appeared as a unique protein of Mr 37.10(3) in SDS-polyacrylamide gel electrophoresis. Rat kidney and adipose tissue were the only nonhepatic tissues showing a cofactor-GSSG deinhibitory effect on both dehydrogenases of the oxidative phase of the pentose phosphate cycle. The deinhibitory activity, also corresponding with a cellular component of Mr 10(5), was only diet-inducible in adipose tissue. The neutralization of the kidney and adipose tissue deinhibitory activity by rat liver cofactor antibodies suggested that there was a structural relationship between the cofactors prepared from these tissues. PMID- 2914148 TI - Compartmentation of dicarboxylic acid beta-oxidation in rat liver: importance of peroxisomes in the metabolism of dicarboxylic acids. AB - Peroxisomal and mitochondrial beta-oxidation of dicarboxylic acids (DCAs) were investigated and compared. When isolated hepatocytes were incubated with DCAs of various chain lengths, H2O2 was derived from peroxisomal beta-oxidation, the rates of its generation being comparable to those seen with monocarboxylic acids (MCAs), whereas the rates of ketone body production, a measure of mitochondrial beta-oxidation, were much lower than those with MCAs. Peroxisomal beta-oxidation measured by cyanide-insensitive NAD reduction exhibited similar chain-length specificities for both dicarboxylyl-CoAs (DC-CoAs) and monocarboxylyl-CoAs (MC CoAs), except that the activities for DC-CoAs with 10-16 carbon atoms were about half of those of the corresponding MC-CoAs. In contrast, mitochondrial beta oxidation measured by antimycin A-sensitive O2 consumption had no activity for DCAs. In the study with purified enzymes, the reactivities of mitochondrial carnitine palmitoyltransferase and acyl-CoA dehydrogenase for DC-CoAs were much lower than those for MC-CoAs, while the reactivity of peroxisomal acyl-CoA oxidase for DC-CoAs was comparable to that for the corresponding MC-CoAs. Accordingly, the properties of carnitine palmitoyltransferase and acyl-CoA dehydrogenase must be the rate-limiting factors for mitochondrial beta-oxidation, with the result that DCAs might hardly be oxidized in mitochondria. Comparative study of beta-oxidation capacities of peroxisomes and mitochondria in the liver showed that DC12-CoA was hardly subjected to mitochondrial beta-oxidation, and that the beta-oxidation of DCAs in rat liver, therefore, must be carried out exclusively in peroxisomes. PMID- 2914150 TI - Spectroscopical studies on the structural organization of the lectin discoidin I: analysis of sugar- and calcium-binding activities. AB - One of the common characteristics observed in different families of sugar-binding proteins is the presence of aromatic residues in the proximity of the functional sugar-binding site (Quiocho, F. (1986) Annu. Rev. Biochem. 55, 287-315). This general property has made these proteins a very appropriate subject for studies using intrinsic fluorescence assays. In the present report we have studied the sugar binding activity of the lectin discoidin I, using a fluorescence-monitored titration assay. The galactose binding has been estimated, with an affinity constant of 1.8.10(-7) M-1 in the absence of calcium. In the presence of 1 mM Ca2+, the Kd of galactose binding is lowered to 2.7.10(-8) M-1. Calcium binding, by itself, seems to occur as two components with Kd values of 10(-7) and 10(-6) M 1. From these data, and sequence comparison of discoidin I with other lectins, a general model for ligand binding has been proposed in which a sequence from position 176 to 188, together with another region close to an apolar tryptophan residue, most probably Trp-50, would participate in the calcium- and sugar binding site(s) of this protein. PMID- 2914151 TI - Delayed emergence of striatal dopaminergic hyperactivity after anterolateral ischemic cortical lesions in humans; evidence from turning behavior. AB - To test the hypothesis that striatal dopaminergic hyperactivity in humans may be an aftermath of anterior cortical ischemic insults, we utilized earlier observations that in several species, including humans with hemiparkinson's disease, asymmetric striatal dopaminergic activity results in spontaneous asymmetric turning away from the hemisphere with higher dopaminergic activity. In this study, electronic monitoring showed that, compared to normal controls, outpatients with old frontal and inferior-parietal cortical strokes exhibit a marked tendency to turn away from the side of the lesion. This delayed ipsilateral neglect suggests a delayed emergence of lasting ipsilateral striatal dopaminergic hyperactivity after unilateral anterolateral cortical insult in humans. Old ischemic insults to anterolateral cortical areas could be one etiological mechanism in human brain disorders that are associated with cortical dysfunction and delayed subcortical dopamine hyperactivity. PMID- 2914152 TI - Hemispheric asymmetries and schizophrenia: a preliminary magnetic resonance imaging study. AB - A magnetic resonance imaging (MRI) study of 20 chronic schizophrenic outpatients (5 women and 15 men) and 20 healthy volunteers, individually matched for age and sex, was conducted. Schizophrenics showed a statistically significant lateral ventricular enlargement and smaller corpus callosum: brain ratio than controls. There were no statistically significant differences in hemispheric measurements between groups. Nevertheless, we found a wider right frontal width versus the left in the patient group but not in the control group, and more frontal protuberances in the right hemisphere in the patient group. Possible meanings and implications of these findings for a pathophysiological hypothesis are discussed. PMID- 2914153 TI - Cardiovascular responses to cocaine placebo in humans: a preliminary report. AB - Cardiovascular responses after placebo-cocaine injections were in the same direction as the effect of cocaine iv in 22 male volunteers. Subjects received iv placebo in a room where they had been given repeated doses of iv cocaine. The placebo response consisted of an increase from baseline values of systolic and diastolic blood pressure and pulse rate. The control group, 8 subjects, which was not exposed to a conditioning phase, showed a smaller increase in the pulse rate and systolic blood pressure after the placebo injection. The results, in accordance with animal literature, suggest the existence of cocaine-conditioned effects in humans. PMID- 2914154 TI - Circadian rhythms of melatonin and cortisol in aging. AB - The relationship of age to the circadian rhythms of melatonin and cortisol was investigated in 44 men and 27 women (age range 19-89 years). Subjects were physically and psychiatrically normal. Four hourly serial blood samples were drawn from 8:00 AM until 8:00 AM the next day, with additional samples at 10:00 PM and 2:00 AM. The indoor illumination was restricted to 300 lux during day and 50 lux during the night. Plasma melatonin and cortisol were estimated by radioimmunoassay. Results show that the means of melatonin and cortisol values decreased significantly with age when the subjects were divided into three age groups, i.e., 19-25 years, 42-65 years, and 66-89 years. They also showed a significant negative correlation with age. The acrophases of the two hormonal rhythms, however, showed different relationships to age. The acrophase of melatonin rhythm showed a positive correlation with age (r = 0.38, p less than 0.001), and cortisol showed a negative correlation with age (r = -0.56, p greater than 0.001). It is suggested that this may indicate a weakened responsiveness of the circadian system in the elderly to the day-night cycle and an altered relationship between the pacemakers driving melatonin and cortisol circadian rhythms. This may thus represent a biomarker for the intrinsic process of the aging of the brain. PMID- 2914156 TI - Suicidal behavior in depression: relationship to noradrenergic function. AB - We examined for relationships between suicidal behavior and noradrenergic function in depression. We compared depressed patients who had or had never attempted suicide and controls on cerebrospinal fluid, plasma, and urinary indices of noradrenergic function. There was no consistent pattern of significant findings in relationship to depressed patients who had attempted suicide. Thus, these essentially negative results suggest that the noradrenergic system is probably not a major determinant of suicidal behavior in depressed patients. PMID- 2914155 TI - REM latency in Alzheimer's disease. AB - Latency to the first episode of rapid eye movement sleep (REML) has been proposed as a potential biomarker for Alzheimer's disease (AD). In this study, we compared REML values from 28 AD patients and 28 age- and sex-matched controls. We employed multiple definitions of REML and multiple cutoffs to classify patients and controls. Results indicated that the best REML definition and optimal cutoff criterion resulted in only 65% correct classifications. We discuss the longer REML in AD patients relative to controls in terms of both overall sleep disturbance and selective deterioration of the REM-cholinergic system. As REML may be relatively short in other forms of psychopathology (e.g., affective disorders), REML may still hold promise in the differential diagnosis of dementia and pseudodementia. PMID- 2914157 TI - Psychoses associated with propranolol withdrawal. PMID- 2914158 TI - Effects of a suppression test dose of dexamethasone on tryptophan metabolism and disposition in the rat. PMID- 2914159 TI - Thalamic dopamine and norepinephrine ratios in schizophrenia. PMID- 2914160 TI - DST in India. PMID- 2914161 TI - Melatonin secretion and age. PMID- 2914162 TI - Alprazolam for psychotic depression. PMID- 2914163 TI - [Comparative volume of membrane microflora and morphology of the epitheliocytes during irradiation of chronic stomach ulcer with helium-neon laser in association with vagotomy]. AB - Effect of complex influence of subdiaphragmal vagotomy (VT) and experimental chronic gastric ulcers (GU) thrice-repeated radiation with helium-neon laser (HNL) on mucosal morphology and relative membrane microflora (MM) volume has been studied with the methods of transmission electron and light microscopy in 77 Wistar rats. Observed MM relative volume increase in GU and VT decreases with GU HNL radiation. This is due to fundal glands epitheliocytes "disregenerative" alterations decrease. PMID- 2914164 TI - [Characteristics of the cultivation of epidermocytes on collagen substratum]. AB - Epidermocytes obtained from human split-thickness skin were cultured in hypocalcium medium (ion calcium content was 0.14 mM). The half bottoms of culture plastic dishes were coated with collagen film before bringing cells in these dishes. It was proved that epidermocytes attach more quickly to collagen, than to plastic substratum, incorporate H3-thymidine (at early periods of cultivation) with larger rate and form and monolayer more quickly, than on the plastic substratum. PMID- 2914165 TI - [EEG changes and symptomatic parkinsonism after intracaudate administration of dopamine antibodies]. AB - Intracaudate bilateral injection of the dopamine antibodies caused the formation of the generator of pathologically enhanced excitation in caudate nuclei. All the rats exhibited the oligokinesia, rigidity and head tremor were observed in most animals. These abnormalities could be observed during 24 hours. The possible role of dopamine antibodies in parkinsonism pathogenesis is discussed. PMID- 2914166 TI - [Determination of serum and plasma erythropoietin in mice with phenylhydrazine induced anemia]. AB - The simple, specific and sensitive erythropoietin bioassay in serum and plasma from phenylhydrazine treated mice is described, based on H3-thymidine incorporation into divided hemopoietic cells. Spleen cells taken from mice on the third day following the second of 2 daily injections of phenylhydrazine were cultured in 24 hours in the presence of test material. Following incubation for 2 hours with H3-thymidine solution radioactivity was measured. PMID- 2914167 TI - [Effects of K+-depolarization on the physical state of membrane lipids in brain synaptosomes of the rat]. AB - The microstructure of lipid bilayer in synaptosomes from rat brain upon K+ depolarization (30 mM) was studied using the inductive resonance energy transfer (IRET) from proteins to the fluorescent probes, pyrene and DMC (4 dimethylaminochalcone). The effectiveness of IRET was not changed by the K+ depolarization. The monomer-to-eximer ration (Fm285/Fe285) of pyrene fluorescence intensities in IRET was 1.5 times lower upon depolarization than in controls. This suggested a decreased microviscosity of the lipid bilayer in immediate environment to proteins of the synaptosomal membrane. The Fm338/Fee338 ratio as well as polarization of DMC fluorescence indicative of the bulk lipid phase were not altered under these conditions. Neither cytochalasin B not colchicine had any effect on fluorescence polarization of DMC both in control and depolarized synaptosomes. It is suggested that the increased lateral mobility of protein associated lipid molecules found in depolarized synaptosomes may be caused by alterations in the activity of ion channels and ion pumps or by restructuring of the cytoskeletal network. PMID- 2914168 TI - [Cardiodepressive effect of platelet activating factor]. AB - The cardiodepressive effect of PAF has been studied on the electrical and mechanical activities of isolated auricles of guinea pig. Intracellular resting potential, action potential (AP) and isometric contractions elicited by electrical stimulation (0.5 Hz) were measured. PAF (10(-7) M) induced negative inotropic effect, which reached its peak after 5 min with 23.5 +/- 6.6% in respect to prechallenge values (n = 8). After 20 min negative inotropic effect relaxed to 39.6 +/- 8.8%. 1 min after the beginning of washing in Tyrode solution, positive inotropic effect of PAF was evident, that reached its peak (217 +/- 49.5%) after 2 min, decayed after 5-10 min to normal values. PAF did not modify the resting membrane potential, produced a decrease in the amplitude and Vmax of the upstroke AP, shortened the AP duration. Ca-AP and contractions, elicited in partially depolarized myocardium were decreased by PAF (10(-7) M). PAF-produce the change of the AP and the negative effect on auricle contractile force was inhibited in muscles pretreated with 3mM 4 aminopyridine. Histamine (10(-4) M) was also capable of neutralizing the depressant effect of PAF. The obtained results suggested that PAF effects on the membrane of cardiac cells could be related to a change in Ca and K conductance. PMID- 2914169 TI - [Generation of blood anticoagulant and fibrinolytic activity after intravenous administration of protein C-a in rats]. AB - Protein C--vitamin K-dependent protein of the blood coagulation system possessing anticoagulant and fibrinolytic activities was under investigation. Activated partial thromboplastin time was shown to prolong to 214 +/- 8.9% from the first minute after intravenous administration of 0.51 mg per rat bovine protein Ca. After 5 minutes the activity of plasminogen activators increased to 339 +/- 52.8%. Both effects gradually diminished and came back to the starting level within 60-90 minutes. The factor V activity reduced two-fold and didn't return to basal level. We propose that protein Ca reveals its enzymatic activity within first minutes after administration and is blocked then with its inhibitor. PMID- 2914170 TI - [Effects of preliminary fasting on the development of D-galactosamine-induced acute lesion of the liver in rats]. AB - The effect of 48-hour preliminary fasting on the development of acute hepatitis in 24 h after the use of 1,855 mmol D-galactosamine per 1 kg bw has been studied on rats. Both intensification of dystrophic and necrotic processes in the liver and aggravation of ultrastructural changes and disorders have been observed. Concentrations of reduced glutathione in the liver and D-glucaric acid in the urine are not changed under the effect of intoxication. PMID- 2914171 TI - [Primary structure of histidine decarboxylase]. AB - The results of investigation of the primary structure of the Histidine Decarboxylase Micrococcus sp. n. are reported. A comparison of the primary structure of the Histidine Decarboxylase Micrococcus sp. n. with that of the Lactobacillus 30a enzyme suggests the alignment with a 52% identity. It is therefore highly probable that two proteins have evolved from common ancestry. The conservative amino acid sequences with residues (pyruvate, cysteine) of the active center have been found. PMID- 2914172 TI - [Lowering of adriamycin toxicity by its combined administration with a copper Cu 2 complex]. AB - Cu-2, a new Soviet copper-complexed cytostatic, decreased acute and hematologic toxicity after lethal doses of adriamycin (AD) were given to male CBA mice. Cu-2 (3.5 mg/kg) was first injected 10 minutes after AD was given, and a second injection followed 50 minutes after the first. Relative to controls given AD alone, the mortality of Cu-2 treated mice was decreased and their lifespan increased. Leukopenia also was less pronounced and of shorter duration. The observed effect of Cu-2 may be related to its superoxide dismutase activity, which may inactivate free radical by-products of AD metabolism known to contribute significantly to the toxicity of this anti-cancer antibiotic. PMID- 2914173 TI - [Neuroanatomical dissociation of reinforcing and analgetic effects of morphine]. AB - Pain-relieving and reinforcing effects of morphine after microinjections into brain structures have been studied. Reinforcing effects were revealed after administration into n. accumbens, while analgesic--after injections into periventricular area of the midbrain and dorsomedial hypothalamus. Data obtained demonstrate neurotopographic heterogeneity of two important effects of morphine. PMID- 2914174 TI - [Effects of corazol on the dynamics of membrane-bound calcium in the structures of the cerebral cortex]. AB - Using the complex methodical approach on the basis of in vivo microscopy and chlortetracycline fluorescent probe of the cat brain cortex preparation the authors studied the changes in the content of the bound calcium in the structures of II-III motor cortex layers in response to influence by metrasol. Correlation between rapid decrease of some part of the bound calcium and development of neuron seizures was discovered. Moreover process of calcium absorption by intracellular membranes in response to influence of metrasol in high doses was revealed. Apparently functional different intracellular membranes are involved in this process. PMID- 2914175 TI - [Effects of repeated acupuncture action on pain sensitivity and beta-endorphin contents of the hypothalamus and midbrain of the rat]. AB - Changes in latencies (L) of nociceptive (NC) reactions of hot plate (HP) tail flick (TF) tests and dynamics of beta-endorphin (beta-ED) in hypothalamus and midbrain were studied in albino rats receiving 15 sessions of acupuncture (A) (20 min daily in bilateral Ho-Ku). It was shown that repeated A facilitated prolongation of LHP and LTF as compared to baseline and control levels. A decrease of the anti-NC systems capacity for activation in response to each A stimulation was observed. The dynamics of beta-endorphin in hypothalamus showed an opposite tendency as compared to that in midbrain. It is suggested that such a correlation of beta-ED activities in midbrain and hypothalamus might be one of the reasons for anti-NC mechanisms adaptation to A. PMID- 2914176 TI - [Ultrastructural analysis of interactions of neutrophil leukocytes and macrophages in the center of inflammation]. AB - The authors have developed the method of investigating the interaction between neutrophil leukocytes and macrophages using a modified model of experimental peritonitis by Gallily and Feldman. The results of electron microscopy studies with quantitative assessment of phagocytosis allowed to demonstrate the sequence of staphylococcus phagocytosis in the peritoneal cavity of rats during the development of experimental peritonitis as well as the interaction between neutrophils and macrophages. PMID- 2914177 TI - [Characteristics of the membranes and functional activity of phagocytic alveolar macrophages]. AB - Alveolar macrophages (AM) accumulate products of lipid peroxidation (PLP) in the time of phagocytosis of zymosan particles (ZP) during 4 hours, that lead to increase of lipid viscosity and decrease surface membrane area, which were studied by fluorescent probes pyrene and HSPH-14. Preliminary stimulation of AM by i/v ZP-injection of A(100 mg/kg before 5 days) lead to a decrease of lipid membrane viscosity and intensification of AM functional activity. During phagocytosis of ZP experimental cells accumulate much less PLP, than control cells, and promote support of viscosity on a more low level, and functional activity (phagocytic, adhesion properties)--on more high level, than in control cells. PMID- 2914178 TI - [Role of the rise of pressure in the pulmonary artery in the distribution of perfusion and gas exchange in bronchial obstruction]. AB - The experiments on the dogs revealed that the damage of lobar bronchus conduction resulted in the decrease of O2 tension in pulmonary venous blood of this lobe. The decrease in the ventilation and blood flow was found in the zone of obstruction by using tracers 133Xe and 99mTc. The pressure rise in the pulmonary artery caused by the spread of bronchial obstruction is one of the factors promoting the redistribution of perfusion into the reserve zones of lungs. The decrease of pressure by the ganglio-blocking preparation results in the increase of arterial hypoxemia. PMID- 2914179 TI - [Suppression of Lewis carcinoma metastasis in mice by an interferon-inducing vasodilator curantil]. AB - The intravascular (iv) or intramuscular (im) inoculations of a suspension of Lewis carcinoma cells induced metastatic tumor nodules in the lungs of C57Bl/6 mice. The administration of curantil (dipyridamole) (500 mg per 20 g-mouse, per os) once a week beginning one day after iv tumor cells inoculation (2 X 10(5) cells) reduced 4-fold the number of tumor nodules. The administration of curantil one day after im tumor cells inoculation (2 X 10(6) cells) reduced 2-fold the number of tumor nodules. The combined treatment of curantil (4-, 10-days after inoculation) and well-known inducer of interferon poly I:poly C (50 mg per 20 g mouse, 1-, 7-, 14-days after inoculation tumor cells) had no synergistic effect. PMID- 2914180 TI - [Morphogenesis of neural derivates after transplantation of the rat embryo telencephalon to the testis of sexually mature animals]. AB - Some aspects of proliferation (the number of DNA synthesizing cells) and differentiation of forebrain (telencephalon) isolated from a 14.5 day old rat embryo and then transplanted into the testis of syngenetic animals were studied for 90 days. The embryonic cells proliferated for 12 days then their differentiation started and many types of differentiated neuronal and glial cells of the definitive brain were found in the transplant. Histological structure of the transplant was without cytoarchitecture of cerebral cortex. The comparison of the obtained data and literature allows us to make a conclusion that realization of morphogenetic potencies of the rat forebrain anlage are the same not only after transplantation into definitive brain, but after being transplanted into different ectopic places; including testis. PMID- 2914181 TI - [Cellular repair of sublethal radiation damage in 2 subpopulations of the CFUs from embryonal liver and bone marrow of adult mice]. AB - The authors studied the ability of the CFU-s, forming colonies on the 8 and 11 day after transplantation of cells from fetal liver (FL) of 14-18 day gestation and adult mouse bone marrow (BM), to repair the sublethal radiation damages (SRD), according to Elkind's model. The ability to repair the SRD of 11-day CFU-s (both EL- and BM-derived) was lower than the ability of 8-day CFU-s. Both subpopulations of CFU-s (as 8-, as 11-day) from FL have a reduced index of SRD reparation as compared with the corresponding meanings for BM. PMID- 2914182 TI - [Sensitivity of the rabbit embryonal Leydig cells to the action of different pituitary hormones]. AB - Leydig cells reaction of rabbits testis to choriogonin action has been investigated during the prenatal period of ontogenesis. It has been found, that these cells sensitivity to the hormones studied has been detected at the early stages of embryogenesis. The specialization of Leydig cells response to choriogonin, thyrotrophin and prolactin in the process of prenatal period has been shown. PMID- 2914183 TI - [Comparative radiosensitivity of CFUs of the mouse bone marrow and embryonal liver forming 7- and 11-day colonies]. AB - The authors studied the radiosensitivity of CFU-s, forming 7- and 11-day colonies from fetal liver (FL) of 14 and 17 day gestation and bone marrow (BM) of adult mice. The index of D0 for 7-day colonies, formed by CFU-s from 14-day, 17-day FL and BM was 2.02; 1.57 and 0.78 Gy, accordingly. 11-day CFU-s both from FL, and from BM did not distinguish statistically at their radiosensitivity (their D0 was 1.25 Gy). PMID- 2914184 TI - [Identification of digitonin binding sites on the plasma membrane of the rabbit aorta endotheliocytes]. AB - Specific reagents comprising digitonin bound to latex spheres were used as visual markers for the detection of cholesterol sites on the endothelial cell surface by scanning electron microscopy. The distribution of latex markers in the plasmolemma of the endothelial cells was investigated. These markers have strong bonds with the ligands. This interaction guarantees high specificity of binding between labeled markers and cellular membrane cholesterol. PMID- 2914185 TI - [Early post-toxic defects in hepatocyte membranes revealed by electron microscopy with the aid of a lanthanum transmembrane tracer]. AB - At early stages of CCl4 treatment defects of hepatocyte membranes are formed as a result of free radical oxidation lipids and Ca2+ accumulation by cells from extracellular media. The formation of membrane's pores precedes the development of ultrastructural changes of hepatocytes during CCl4 treatment and this is the result of membrane damage. PMID- 2914186 TI - High-resolution computed tomography in pulmonary cystic fibrosis. AB - Twenty-one patients with established cystic fibrosis were examined using high resolution, narrow-section computed tomography. The bronchiectasis of cystic fibrosis is described and is shown to be characteristic in many respects. Computed tomography was found to be more accurate than standard radiography in locating the disease process and demonstrated pleural involvement which was not apparent on chest radiographs. PMID- 2914187 TI - Some indicative parameters on diagnostic radiology in Spain: first dose estimations. AB - The Medical Physics Group at the Complutense University of Madrid has been co ordinating, for approximately 1 year, a project on optimization of radiation protection in diagnostic radiology, in co-operation with the other states of the European Community. Exhaustive data on the subject, which offer accurate results on patient dosimetry for the different types of examination, are the final aim of the project. So far, it has been possible to analyse in detail the data from the National Institute of Health (NIH), which manages the care of about 96% of the Spanish population, plus the findings from several hospitals, outpatient centres and private clinics of the community of Madrid, which allowed us to perform the first dose estimations and to extrapolate them to the rest of Spain. The following estimations are presented: annual frequency of different examinations, their variation from 1985 to 1986, number of diagnostic rooms used for a given minimum of annual examinations, organ doses for different examinations, effective dose-equivalent, genetically significant dose for some examinations, as well as the collective dose. PMID- 2914188 TI - Transient diverticula of the colon. AB - Transient diverticula are radiological phenomena that can be observed in a minority of patients undergoing barium enema. Radiographs before and after smooth muscle relaxation are required. Diverticula seen on the early radiographs may, in some patients, disappear following the intravenous administration of 20 mg hyoscine-N-butylbromide (Buscopan). Using this technique in 441 examinations, transient diverticula have been observed in 18 patients (4.1%). They exhibit many features of established diverticula which suggests that they represent an incipient stage of the disease. PMID- 2914189 TI - Technetium-99m hydroxymethylene diphosphonate scanning of acute injuries to the lateral ligaments of the ankle. AB - Technetium-99m hydroxymethylene diphosphonate scans were performed on 29 consecutive patients with acute ankle ligament injuries. Scanning reliably differentiated a severe from a minor injury. Severe injuries gave a diffuse uptake on the scan and the minor injuries a more localized increase in uptake. PMID- 2914190 TI - Cell kinetic changes in the follicular epithelium of pig skin after irradiation with single and fractionated doses of X rays. AB - Changes in the cell kinetics of the follicular epithelium of the pig have been studied after irradiation with single and fractionated doses (30 fractions/39 days) of X rays and the results compared with previously published data for the epidermis. In the follicular epithelium there was an initial degenerative phase, during which the rate of cell depletion was independent of the radiation dose and the mode of administration. Evidence for repopulation was seen between the 14th and 18th days after single doses (15 or 20 Gy) and by the 28th day after the start of irradiation with fractionated doses (52.3-80.0 Gy). However, the degree of cell depletion and the subsequent rate of repopulation were independent of dose. The regenerative phase was characterized by an increased cell proliferation as indicated by an elevation of the labelling index. Islands of cells (colonies), with an appearance similar to cells in the normal follicular epithelium, were seen 18 days after a single dose of 20 Gy and 42 days after the start of fractionated irradiation. When compared with the epidermis, the follicular epithelium exhibited considerably less evidence of damage after both single and fractionated doses of X rays. There was a lower incidence of degenerate cells and reduced levels of cell depletion in the follicular epithelium, suggesting that cells from this region play an important role in the repopulation of the epidermis after high-dose irradiation. PMID- 2914191 TI - Precision of determining compliance with prescribed fields from conventional portal films. AB - Three hundred and seventy measurements of field placement errors (FPEs) have been made by a total of 16 observers on 20 prescription-treatment film pairs taken during routine radiotherapy for cancer of the prostate. Analysis of the distributions of the measured FPEs has yielded the precision of the measurement under a variety of conditions. We report here the influence on the precision of determining FPEs of the following factors: the clinical duties of the observers, the quality of the treatment film, the relative magnification of prescription and treatment films, and whether double-exposure techniques were employed. PMID- 2914192 TI - Discriminant analysis on the treatment results of interstitial radium tongue implants. AB - Discriminant analysis was carried out for 48 tongue cancer patients who were treated with radium single-plane implantation. The 48 patients were grouped into 32 successfully cured without complications, five successfully cured with complications, six successfully cured but requiring additional boost therapy and five with local recurrence. To evaluate the relation between the dose distribution and the local treatment results, the analysis was based on a volume dose relationship. The functions introduced by this discriminant analysis were linear, and the parameters used were modal dose, average dose and shape factors of histograms. Each group of treatment results had a correction rate of greater than 80%, except for the successfully cured group with ulcers. The discriminant functions were useful as an index to obtain a final clinical treatment result at the early time of implantation, and these functions could be used as a criterion for the optimal treatment of tongue carcinoma. We were also able to recognize the limitation of the actual arrangement of sources in the single-plane implant. PMID- 2914193 TI - Results of treatment of carcinoma of the uterine cervix using the Newcastle afterloading technique. AB - Eighty-seven patients with carcinoma of the uterine cervix were seen between 1 August 1977 and 31 December 1985. Seventy-one patients were treated radically. A combination of intracavitary radiotherapy, using the Newcastle manual afterloading technique, and external-beam radiotherapy was used. The actuarial 4 year survival for all Stage 1 cervical carcinomas was 84.9%. For Stage 2 cancers the actuarial local control rate was 71.1% and the survival 49.2% and for Stage 3 cancers the 4-year actuarial local control rate was 24.3% and the survival 14.8%. Complications of treatment were confined to the bowel and bladder and occurred in 11.5% of cases. The results of treatment of Stage 1 cancer suggest that the intracavitary technique gives a satisfactory distribution of radiation. The results of treatment of more advanced cases are disappointing and suggest that improvements are possible for some patients (i.e. wedge malalignment patients). There is sufficient flexibility in the technique for it to be applied satisfactorily for most anatomical situations. PMID- 2914194 TI - An indwelling intrauterine tube to facilitate intracavitary radiotherapy of carcinoma of the cervix. PMID- 2914195 TI - A source localizing technique for the microSelectron-HDR afterloading system. PMID- 2914196 TI - Anomalous superior vena cava causing non-visualization of the lungs in perfusion scintigraphy. PMID- 2914198 TI - Primary extranodal lymphoma in muscle. PMID- 2914197 TI - Ossified leiomyoma of the stomach: demonstration on computed tomography. PMID- 2914199 TI - A colonic double bubble. PMID- 2914200 TI - Functional changes in the irradiated rat ureter: assessment by transit-time renography. PMID- 2914201 TI - Late normal tissue reactions in patients with breast carcinoma. PMID- 2914202 TI - Diagnostic radiation, pregnancy and termination. PMID- 2914203 TI - Leakage from a caesium-137 needle. PMID- 2914204 TI - Proceedings of the British Institute of Radiology. Too much radiation in radiodiagnosis? Abstracts. London, March 9, 1988. PMID- 2914205 TI - The astroglial response to autonomic tissue grafts. AB - Autonomic (superior cervical) ganglia were grafted either into the IV ventricle where minimal trauma occurred or directly into the cerebral cortex which was necessarily traumatic. Previous studies have shown that host astroglia may migrate into autonomic tissue grafts. The purpose of the present study was to compare and contrast the astroglial response in allo- and autografts. By monitoring the host response in the two model sites using glial fibrillary acidic protein (GFAP) immunostaining in 1 micron plastic sections we sought to determine the role of injury stimulus in astroglial migration. In addition, these models could be used to investigate any potential differences in glial reactivity produced by allo- or autograft antigenic stimulation. In both ventricular and parenchymal locations, astroglia migrated progressively into allografts. Migration, which could have taken place along anastomotic vascular connections, began after one week and was continual, eventually replacing graft neural tissue. Astrocytic processes appeared enlarged and highly immunoreactive only as they entered the allografts or were in close association with the choroid plexus; adjacent host astrocytes were unaltered. Glial migration was greatly reduced in ventricular autografts but in the parenchymal site was nearly comparable to that of allografts. It was suggested that certain immunological factors may be involved in glial reactivity or migration considering the observed differences in the non-traumatic model whereas tissue damage stimulus played a major role in migration in both allo- and autografts. In no instances were typical astrocytic end-feet found on the autonomic graft vessels. The host astrocytic response to grafted autonomic tissue occurred significantly later (5-7 days) than the host endothelial response. This observation indicates that the graft vessels were original, intrinsic ones and the astrocytic invasion played no role in influencing endothelium with regards to brain-barrier properties. PMID- 2914206 TI - Immunocytochemical characterization of neuron-rich rat brain primary cultures: calbindin D28K as marker of a neuronal subpopulation. AB - The function in neurons of the vitamin D-dependent calcium ion-binding-protein of 28 kDa mol. wt., calbindin D28K, is unknown. In order to find a simple system for studying the function of this protein, neuron-rich primary cultures derived from brains of 16-day-old rat embryos were analyzed for the presence of calbindin D28K by immunocytochemical mono- and double-labelling techniques. The studies were carried out between the 5th and 23rd day after seeding. In contrast to the neuronal marker neuron-specific enolase which was found in nearly all cells in the culture, calbindin D28K was expressed only in a subpopulation of neurons. Calbindin D28K-positive cells were intensely stained in their cell bodies and were also stained in their processes. Astroglial cells identified by the presence of the processes. Astroglial cells identified by the presence of the specific marker glial fibrillary acidic protein did not express calbindin D28K. Therefore, calbindin D28K is a useful marker for defining a neuronal subpopulation in neuron rich primary cultures. Such cultures may be employed as a tool in searching for function(s) of calbindin D28K. PMID- 2914207 TI - GABA-immunoreactivity in ganglion cells of the rat retina. AB - Ganglion cells in the rat retina were labeled with the fluorescent dye, Diamidino yellow, by retrograde transport from the superior colliculus and subsequently reacted for GABA-like immunoreactivity with a rhodamine-conjugated antiserum. Examination of sectioned retinas by fluorescence microscopy showed double labeling in approximately 6% of the ganglion cells. The presence of GABA in these neurons suggests that they may be involved in providing direct inhibitory input to the rat tectum. PMID- 2914208 TI - The pretectum as a site for relaying dorsal column input to thalamic VL neurons. AB - Intracellular recording techniques were used to study dorsal column input to 122 feline ventral thalamus (VL) relay neurons, before (61 cells) and after (61 cells) lesioning the pretectum. Prior to the lesions, 75% (46/61) of the neurons responded with short and longer latency postsynaptic potentials to dorsal column stimulation. Latencies of the postsynaptic potentials ranged from 4 (short) to 20 ms (long). After the lesions, only long latency responses were encountered, and those responses were seen in only 16% (10/61) of the cells. These data indicate that the pretectum may play an important role in mediating dorsal column information to VL, ultimately influencing cerebellar commands to the motor cortex. PMID- 2914209 TI - The cholinergic input to the superficial layers of the superior colliculus: an ultrastructural immunocytochemical study in the ferret. AB - The cholinergic innervation of the superficial layers of the ferret's superior colliculus was investigated with a combination of electron microscopy and choline acetyltransferase immunohistochemistry. Cholinergic boutons in the superficial layers of the superior colliculus possess spherical vesicles and make predominantly asymmetrical synapses onto the profiles of small dendrites, as do the terminals of cortical and retinal axons. In most areas of the brain studied so far, cholinergic terminals tend to form synapses of the symmetrical variety. PMID- 2914210 TI - Cholinergic activation of medial pontine reticular formation neurons in vitro. AB - Direct microinjection of cholinergic compounds into pontine reticular formation furnishes an excellent phenomenological model of the rapid eye movement phase of sleep (REM), but the mechanisms underlying this effect and whether they mimic the cellular events of natural REM remain unknown. Data presented here from intracellular recordings in vitro in the rat demonstrate that two-thirds of medial pontine reticular formation neurons respond to application of 0.5-1.0 microM carbachol with a depolarization characterized by a decreased conductance and a linear I/V curve. The resultant mimicry of REM cellular events by carbachol extends to membrane potential depolarization, increased cellular excitability, enhancement of PSPs from reticular stimulation, and the absence of a burst discharge pattern. The presence of these effects with tetrodotoxin and their blockade by atropine imply a direct, muscarinic cholinergic mediation. Other neurons tested responded with either a biphasic hyperpolarization-depolarization or a hyperpolarization. The hyperpolarization was associated with an increased conductance which exhibited pronounced inward rectification, an effect novel for cholinergic agonists in vertebrate CNS but described in heart cells. PMID- 2914211 TI - Paradoxical sleep deprivation does not affect neuronal excitability in the rat hippocampus. AB - Before, during and after paradoxical sleep deprivation, field potentials, evoked in the CA1 region and in the fascia dentata of the hippocampus by means of paired pulse stimulation, were measured. Paradoxical sleep deprivation was applied for 3 days, using the platform and the pendulum technique. No changes were observed on evoked field potential amplitude, population spike or paired pulse depression during and after the deprivation period. These results suggest that the neuronal excitability in the rat hippocampus, measured with the evoked potential technique, does not change as a result of paradoxical sleep deprivation. PMID- 2914212 TI - Habituation of monosynaptic field potentials in the dentate gyrus of freely moving rats interferes with LTP. AB - In 30 male Wistar rats, monosynaptically evoked field potentials in the dentate gyrus were registered under different conditions of repetitive stimulation and the long-term changes in synaptic transmission studied. Low-frequency stimulation induces a habituation-like decrement of the field-EPSP, but not of the population spike which interferes with the maintenance of LTP when administered after tetanic stimulation. The habituation-like response decrement, however, does not influence paired pulse-depression seen with an interstimulus interval of 20.0 ms. The paired pulse-plasticity, on the other hand, can be influenced by the tetanic stimulation (diminution of facilitation or depression), being dependent on the intensity of test stimuli. The results can be interpreted in terms of a complex influence of low-frequency- and tetanic stimulation on the elements of the dentate local circuitry and point to the necessity of considering long-term plastic changes in the investigation of substance- or stimulation-induced deviations of neuronal responses. PMID- 2914213 TI - Absence of electrographic seizures after transient forebrain ischemia in the Mongolian gerbil. AB - EEG was continuously recorded from Mongolian gerbils for 4 days after transient bilateral forebrain ischemia, to determine whether ischemic brain damage in this species is necessarily associated with seizures. Gerbils were chronically implanted with EEG recording electrodes in hippocampal area CA1, striatum and frontal neocortex and were subjected to a 5-10 min occlusion of both common carotid arteries. During the first few hours after the occlusion, the EEG was dominated by slow waves similar to those recorded from human brain after a damaging episode of cerebral ischemia. Amplitudes of the hippocampal and striatal EEG declined markedly with time, presumably as a result of neuronal degeneration. Ictal activity was never recorded, even from animals that suffered extreme damage to the hippocampal formation and striatum. Therefore ischemic brain damage in the gerbil does not result from seizure activity. PMID- 2914214 TI - Adenosine deaminase containing fiber pathway from the superior colliculus to the lateral posterior nucleus of the rat. AB - Presence of a projection containing adenosine deaminase (ADA)-like immunoreactivity from the stratum opticum (SO) to the dorsomedial portion of the lateral posterior nucleus of the thalamus (LPN) of the rat was demonstrated using a method combining retrograde tracing by horseradish peroxidase (HRP) and immunohistochemistry for ADA. In the caudal two thirds of the LPN, a clearly delimited ADA-like immunoreactive fiber plexus was located. Injection of HRP into the lateral posterior nucleus labeled many neurons in the medial portion of the SO where medium-sized neurons with ADA immunoreactivity were concentrated. Simultaneous immunostaining showed that some of the HRP-labeled neurons are ADA positive. PMID- 2914215 TI - Low frequency stimulation of the locus coeruleus reduces regional cerebral blood flow in the spinalized cat. AB - Regional cerebral blood flow (RCBF) was studied during low frequency (15/s) and high frequency (50/s) electrical stimulation of the locus coeruleus (LC) in the alpha-chloralose-anesthetized cat using the freely diffusible tracer [14C]iodoantipyrine and regional brain dissection. The responses were determined in animals spinalized at the C1/C2 level to eliminate systemic effects of pontine stimulation such as alterations in blood pressure and heart rate. The spinalization, itself, did not alter resting RCBF or reactivity to hypercapnia. Low frequency stimulation reduced regional cerebral blood flow in the cortex, basal ganglia and white matter of the corpus callosum. The reductions in RCBF were maximal (35%) in the occipital cortex whereas no changes were seen in the colliculi. No changes were seen in any brain areas with high frequency stimulation. The relevance of this brainstem effect on cerebral blood flow to pathological states such as stroke and migraine is discussed. PMID- 2914216 TI - Memory enhancement with intra-amygdala post-training naloxone is blocked by concurrent administration of propranolol. AB - Sprague-Dawley rats were first trained on an inhibitory avoidance task (IA) and then, two weeks later, on a Y-maze discrimination task (YMD). Bilateral intra amygdala injections were given through implanted cannulae immediately post training. Retention was evaluated one week following training on each task. Naloxone (0.1, 0.3 or 1.0 microgram) facilitated retention performance in both tasks. The most effective doses were 0.1 microgram for the IA task and 0.3 microgram for the YMD task. Since naloxone (0.1 microgram) did not affect retention when administered via cannulae implanted in either the caudate-putamen or cortex dorsal to the amygdala, the effects of intra-amygdala naloxone is not due to diffusion of the drug to these brain regions. Intra-amygdala injections of the beta 1,2-adrenoceptor blocker propranolol (0.3 microgram) blocked the memory enhancing effects of intra-amygdala naloxone (IA: 0.1 microgram; YMD: 0.3 microgram) administered concurrently immediately post-training. We interpret these findings as indicating that the enhancing effects of intra-amygdala naloxone are mediated by the activation of beta-noradrenergic receptors within the amygdala. Such effects are presumably due to blocking of inhibitory effects of opioid peptides on the release of norepinephrine. PMID- 2914217 TI - Failure to detect antibody to bovine respiratory syncytial virus in bovine fetal serum. AB - Sera obtained from 147 bovine fetuses estimated to be between 120 and 270 days of gestation at an abattoir were tested for antibody to bovine respiratory syncytial virus. Antibody to bovine respiratory syncytial virus was not detected in any of the sera examined. Based on the results of this study and a review of the literature, it appears that transplacental infection by bovine respiratory syncytial virus does not occur, or is uncommon. PMID- 2914218 TI - Detection of African swine fever virus antibodies by immunoblotting assay. AB - An immunoblotting assay has been adapted to detect antibodies against African swine fever virus. The electrophoretic transfer of proteins and the immunoreaction conditions were optimized, using 4 mA/cm2 of current intensity and 10 micrograms of soluble cytoplasmic antigen of infected cells per strip. Filters of polyvinylidene difluoride showed the highest capacity for protein absorption, but nitrocellulose filters showed lower backgrounds. The specificity and the pattern of the proteins induced by African swine fever virus that react with the antisera were determined in immunoblotting assay, IP30 being the most reactive protein. PMID- 2914219 TI - Delayed resumption of development of inhibited Cooperia oncophora in a yearling calf. AB - During a study of larval inhibition, resumption of development of Cooperia oncophora was observed in one calf to occur over a prolonged period of time. This animal had grazed for 14 weeks, was treated with thiabendazole and stabled for eight weeks prior to grazing the same pasture for ten days in late fall. A marked increase in Cooperia egg output started about six months after restabling. Worm egg outputs persisted for about 14 months with counts of up to 1000 eggs per gram during the first eight months of this period followed by a period with low counts of 50 to 150 eggs per gram. PMID- 2914220 TI - Experimental trichinosis in sheep. AB - Trichinella spiralis spiralis infections were established in sheep by administering infective larvae via gavage or feeding infected musculature. Trichinella spiralis nativa infective larvae had a low infectivity for sheep although light infections may be established in some animals with large infective doses. For the most part, sheep were averse to ingesting musculature mixed in a grain ration unless it was camouflaged with molasses. The heaviest infections usually occurred in the masseter muscle. The fact that sheep are averse to ingesting muscle tissue may reduce the likelihood of trichinosis. Anti Trichinella antibodies to both T: spiralis spiralis and T. spiralis nativa were produced as demonstrated by the enzyme-linked immunosorbent assay. Seroconversion occurred in several sheep challenged with T. spiralis nativa even though larvae were not recovered from the musculature by pepsin-digestion. PMID- 2914221 TI - Pharmacokinetics and body fluid and endometrial concentrations of ormetoprim sulfadimethoxine in mares. AB - Six healthy adult mares were each given an oral loading dose of ormetoprim(OMP) sulfadimethoxine (SDM) at a dosage of 9.2 mg of OMP/kg and 45.8 mg of SDM/kg, followed by four maintenance doses of 4.6 mg of OMP/kg and 22.9 mg of SDM/kg, at 24 h intervals. Ormetoprim and SDM concentrations were measured in serum, synovial fluid, peritoneal fluid, cerebrospinal fluid, urine and endometrium. The highest mean serum OMP concentration was 0.92 micrograms/mL 0.5 h after the first dose; the highest mean SDM concentration was 80.9 micrograms/mL 8 h after the first dose. The highest mean synovial fluid concentrations were 0.14 microgram of OMP/mL and 28.5 micrograms of SDM/mL 12 h after the first dose. The highest mean peritoneal fluid concentrations were 0.19 micrograms of OMP/mL 6 h after the first dose and 25.5 micrograms of SDM/mL 8 h after the fifth dose. The highest mean endometrial concentrations were 0.56 micrograms of OMP/g and 28.5 micrograms of SDM/g 4 h after the fifth dose. The mean cerebrospinal fluid concentrations were 0.08 micrograms of OMP/mL and 2.1 micrograms of SDM/mL 5 h after the fifth dose. Mean trough urine drug concentrations were greater than or equal to 0.4 micrograms of OMP/mL and greater than or equal to 172 micrograms of SDM/mL. Two of the mares were each given a single intravenous (IV) injection of OMP and SDM at a dosage of 9.2 mg of OMP/kg and 45.8 mg of SDM/kg. Excitation and muscle fasciculations were observed in both mares after IV administration and all scheduled blood samples could be collected from only one of the two mares.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2914222 TI - Effects of perinatal high dose dexamethasone on skeletal muscle development in rats. AB - Five litters of suckling rats were given either dexamethasone (DEX), 1 mg/kg, subcutaneously, three times daily (n = 4/litter) or vehicle control (n = 4/litter) from day 3 through day 7 after birth. Rats were weighed weekly and were weaned on day 30. On day 60, rats were killed and the soleus (SOL) and extensor digitorum longus (EDL) were removed for the following analyses: 1) wet weight, 2) light microscopic examination of hematoxylin and eosin stained transverse sections, 3) quantitative morphometric analysis of myosin ATPase stained transverse sections (fiber numbers, fiber type percentages and mean fiber diameters), and 4) DNA (total and mg/g wet weight). The following parameters were significantly reduced in treated rats: 1) body weight, 2) wet weight of SOL and EDL, and 3) mean diameter of SOL type I fibers. There was a trend for total DNA of SOL and EDL to be decreased in treated rats but this was not statistically significant. In a second experiment, pregnant rats (n = 4) were given DEX, 1 mg/kg, subcutaneously, twice daily, on days 17 and 18 of gestation. Two rats served as vehicle controls. The prenatally DEX-exposed rats weighed significantly less on weeks 3, 4, 6, 7 and 8. There were significant reductions in the following parameters for treated rats: 1) SOL wet weight, and 2) total number of SOL type I fibers. There was a trend for SOL DNA to be reduced but this was not statistically significant. PMID- 2914223 TI - Nephrotoxicity of amphotericin B in dogs: a comparison of two methods of administration. AB - Two methods of administration of amphotericin B were compared for their ability to produce nephrotoxicity in 12 dogs. Six dogs received six alternate day doses of amphotericin B: 1 mg/kg administered as a rapid bolus in 25 mL 5% dextrose in water. Another six dogs received alternate day treatments of the same dose of amphotericin B in 1 L 5% dextrose in water over 5 h. Both treatment groups experienced significant reductions in glomerular filtration rate, as measured by inulin clearance, 24 h endogenous creatinine clearance, serum creatinine and serum urea. This reduction in glomerular filtration rate was most marked in the group receiving the drug as a rapid bolus. The inulin clearances decreased from 3.54 +/- 0.30 mL/min/kg (means +/- SEM) on day 0 to 1.15 +/- 0.25 mL/min/kg on day 12 in the slow infusion group and from 3.24 +/- 0.25 mL/min/kg on day 0 to 0.46 +/- 0.11 mL/min/kg on day 12 in the rapid bolus group. Renal lesions characteristic of amphotericin B administration were observed in all dogs tested. The dogs which received amphotericin B as a rapid bolus had a significantly greater number of tubular lesions than the slow infusion group. Systemic side effects, such as vomiting, diarrhea and weight loss, were observed in both treatment groups but were most severe in the rapid bolus group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2914224 TI - Plasma and liver copper values in horses with equine degenerative myeloencephalopathy. AB - Equine degenerative myeloencephalopathy (EDM) is a common spinal cord disease in the horse. The etiology of EDM currently is unknown. In other species, there are similarities in the clinical signs and neuropathological changes observed in EDM and in copper deficiency. The objective of this study was to determine if horses affected with EDM had low levels of plasma or liver copper. Plasma copper values were determined in 25 EDM affected horses and 35 normal horses. Liver copper levels were determined on 13 EDM affected horses and 22 normal horses. Plasma and liver copper values were not significantly lower in EDM affected horses than in control horses. PMID- 2914225 TI - Environmental source of mycobacteriosis in a California swine herd. AB - Between July 1985 and April 1986, mycobacterial lymphadenitis was recorded in six of 2407 slaughter pigs from a commercial swine herd in which the majority of pigs were raised in confinement. Records showed that all six affected pigs had access to dirt-floored pens at least 81 days prior to slaughter. The mycobacteriosis lesion rate for pigs exposed to dirt pens was 9.4% while in nonexposed pigs the lesion rate was zero. The risk associated with movement of pigs from concrete floored pens to dirt pens was evaluated by a field trial. In the field trial, two litters (5 of 15 pigs) exposed to dirt pens at 12-24 days of age but none of nine nonexposed litters (39 pigs) developed lesions. Mycobacterium avium-complex bacteria were recovered from both exposed litters (9 of 15 pigs) but from none of nine nonexposed litters. Serovars of M. avium-complex isolated from trial pigs included 1, 4, 8, 9, the dual serovar 4/8, and an untypable serovar. Incense cedar bark (Calocedrus decurrens) used as a flooring material in the pens was demonstrated to be a potential source of M. avium-complex serovar 9. The dual serovar 4/8 and an untypable M. avium-complex were isolated from the dirt-floored pens. No evidence of cross-transmission of M. avium-complex infection was detected. The sporadic pattern of mycobacteriosis observed in the herd probably resulted from infrequent exposure to a common environmental source. PMID- 2914226 TI - Plasmid mediated antimicrobial resistance in Ontario isolates of Actinobacillus (Haemophilus) pleuropneumoniae. AB - The genetic basis of antimicrobial resistance in Ontario isolates of Actinobacillus (Haemophilus) pleuropneumoniae was studied. Two Ontario isolates of A. pleuropneumoniae were found to be resistant to sulfonamides (Su), streptomycin (Sm) and ampicillin (Amp). Resistance to Su and Sm was specified by a 2.3 megadalton (Mdal) plasmid which appeared to be identical to pVM104, which has been described in isolates of A. pleuropneumoniae from South Dakota. Southern hybridization showed that the 2.3 Mdal Su Sm plasmid was highly related to those Hinc II fragments of RSF1010 known to carry the Su Sm genes, but was unrelated to the remainder of this Salmonella resistance plasmid. Resistance to Su and Amp was specified by a 3.5 Mdal plasmid and appeared identical to pVM105 previously reported. The beta-lactamase enzyme had an isoelectric point of approximately 9.0. Southern hybridization showed no relationship to the TEM beta-lactamase. A third isolate of A. pleuropneumoniae was found to be resistant to chloramphenicol (Cm), Su and Sm by virtue of a 3.0 Mdal plasmid which specified a chloramphenicol acetyl transferase. We conclude that resistance to Su, Sm, Amp and Cm is mediated by small plasmids in A. pleuropneumoniae. Although the Su and Sm resistance determinants are highly related to those found in Enterobacteriaceae, the plasmids themselves and the beta-lactamase determinant are different. PMID- 2914227 TI - Immunization of foxes by the intestinal route using an inactivated rabies vaccine. AB - Approximately 30% of foxes given two doses of an inactivated rabies antigen delivered directly into the intestinal tract developed an immune response as measured by rabies serum neutralizing antibodies. Seven of ten previously immunized foxes showed an anamnestic response following a booster dose of inactivated rabies antigen delivered to the intestinal lumen. Stomach and particularly intestinal contents were destructive to rabies antigen and virus. This effect could be partially neutralized in vitro by the addition of Questran and soybean trypsin inhibitor. Small enteric coated tablets fed to foxes in a hamburger bolus remained in the stomach for up to 13 hours and therefore would provide a poor vehicle for the delivery of antigen to the intestinal tract. PMID- 2914228 TI - Comparison of serum biochemical profiles of male broilers with female broilers and White Leghorn chickens. AB - Male broiler chickens were compared to female broiler chickens and male White Leghorns with respect to a 15-parameter serum biochemical profile at 9, 20, 30 and 42 days of age in order to determine which, if any, of the parameters tested might be useful in the identification of birds susceptible to sudden death syndrome. In comparison to female broilers, male broilers had significantly lower (p less than 0.01) total protein levels at 20 days of age and significantly higher (p less than 0.01) cholesterol levels at 30 days of age. Compared to male White Leghorns, in which sudden death syndrome has not been reported, male broilers had significantly lower (p less than 0.01) levels of cholesterol and creatinine at nine days of age, total protein at 9 and 20 days of age and albumin at 20 days of age and significantly higher (p less than 0.01) levels of potassium at nine days, uric acid at 9, 20 and 30 days, lactate dehydrogenase at 20, 30 and 42 days and cholesterol at 30 days of age. PMID- 2914229 TI - Destruction of Trichinella spiralis spiralis during the preparation of the "dry cured" pork products proscuitto, proscuittini and Genoa salami. AB - Genoa salami, proscuittini and proscuitto were prepared from pork carcasses that were heavily infected experimentally with Trichinella spiralis spiralis. Genoa salami was prepared with salt concentrations of 2.0%, 2.75% and 3.3%. Proscuitto was prepared by two procedures approved by Agriculture Canada. At various times postpreparation, samples of the various cured products were taken and examined by pepsin digestion and rat bioassay for the presence of viable trichinae. Water activity and pH of the cured meat were also determined. Curing of the various products was shown to destroy the Trichinella larvae. Pepsin digestion revealed that larvae progressively became loosely coiled, uncoiled and more subject to digestion (ghost larvae) during the curing process. Rat bioassay revealed the presence of viable trichinae in the proscuitto prepared using a sodium chloride salt mixture at day 34 but not at day 48 postpreparation. All other bioassays carried out on Genoa salami between 13 and 42 days postpreparation, on proscuittini between days 27 and 69 and on proscuitto between days 34 and 69 were negative for viable trichinae. Under the conditions of this study, preparing Genoa salami with salt concentrations as low as 2% did not appear to affect the destruction of Trichinella larvae. PMID- 2914231 TI - Blood gas stability and hematological changes in experimentally-induced acute porcine pleuropneumonia. AB - Blood gas and hematological responses to acute, mild Actinobacillus pleuropneumoniae infection of growing pigs was studied. Six pigs (average weight 10.1 kg) were experimentally infected intranasally with A. pleuropneumoniae serotype 5. Four pigs served as controls. Rectal temperatures and arterial blood for gas analysis and hematology were taken at 0, 8, 16, 24, 48 and 72 h postinfection. All infected pigs became febrile showing clinical signs typical of mild to moderate porcine pleuropneumonia; controls remained asymptomatic. Neutrophilia with bands and lymphopenia were observed only in infected pigs. Arterial partial pressures of O2 and CO2, and pH did not change in infected pigs. All pigs were killed after 72 h, and lungs were examined and cultured. Gross and microscopic lesions consistent with porcine pleuropneumonia were seen in 3/6 and 5/6 infected lungs, respectively. Control lungs were grossly normal with no histological evidence of pleuropneumonia. We conclude that in mild, acute porcine pleuropneumonia as established experimentally, a leukogram typical of acute inflammation and stress is seen; however, hypoxemia and alveolar hypoventilation are not features of this form of the disease. PMID- 2914230 TI - Prognosis in equine colic patients using multivariable analysis. AB - Multiple logistic regression was used to investigate prognosis in 308 horses referred to the University of Minnesota veterinary teaching hospital with colic. Bivariate results identified the following significant individual parameters: absent or hypomotile abdominal sounds, medical or surgical classification, peritoneal fluid total protein, anion gap, serum glucose, capillary refill time, blood pH, heart rate, packed cell volume, base excess, serum chloride, plasma bicarbonate, serum urinary nitrogen and age. Two multivariable prognostic models were developed using logistic regression. Model I (based on 257 cases with a mortality rate of 39%) included age, sex, medical or surgical classification, capillary refill time, packed cell volume and heart rate. Model II (based on 138 cases with a mortality rate of 48%) included age, sex, medical or surgical classification, capillary refill time, serum bicarbonate, serum chloride and respiratory rate. Predictive performance of the models was evaluated by treating the calculated probability of death for each horse as a continuous test result. The influence of varying the probability cutoff point for death on test characteristics (sensitivity, specificity and positive and negative predictive values) was determined. These models have not been validated and thus their performance in a different population is uncertain. PMID- 2914232 TI - Informed consent to HIV testing. PMID- 2914233 TI - Stress among emergency medical staff: the US solution. PMID- 2914234 TI - Licensure: competence to do what? PMID- 2914235 TI - Excrement, effluent and exhalations. PMID- 2914236 TI - Is abortion a medical act? PMID- 2914237 TI - Glass is detectable on plain radiographs. PMID- 2914238 TI - Emergency department overcrowding. PMID- 2914239 TI - How we solved the overcrowding problem in our emergency department. AB - Overcrowding in emergency departments presents serious problems to both patients and hospital staff. At Scarborough (Ontario) General Hospital this problem was becoming potentially dangerous until a hospital committee instituted a series of changes that dramatically improved the situation. A geriatrician was appointed to assess and care for the increasing number of elderly and chronic care patients. The beds in various services were reallocated, and more beds were given to the medical service. Surgeons agreed to perform more surgery on an outpatient basis, and the Short-Stay and Ambulatory Procedures units were expanded to handle more procedures. In addition, the implementation of a physician-managed admission system ensured the appropriate admission of patients. The entire system is monitored, and the committee meets regularly to deal with any problems. PMID- 2914240 TI - Endocervical Chlamydia trachomatis infection in Canadian adolescents. AB - The highest prevalence rate of sexually transmitted chlamydial infection is among adolescent girls. To determine the rate among predominantly asymptomatic girls who were seen at a pediatric gynecology unit and to identify those at high risk we screened 541 such patients from Jan. 1 to Dec. 31, 1986, by means of direct fluorescent antibody testing; 422 (78.0%) were asymptomatic. The most common reason for presentation was a request for contraceptive advice (the reason for 59.2% of the patients). Of the 446 patients (82.4%) who were sexually active 66 (14.7%) had evidence of chlamydial infection; none of the 93 sexually inactive patients were infected. Neisseria gonorrhoeae was isolated from eight (1.5%) of the patients. The risk factors that correlated with chlamydial infection were abnormal vaginal discharge, abdominopelvic pain and an abnormal Papanicolaou test result. Because of the high morbidity rate associated with genital chlamydial infection and the high prevalence rate among adolescent girls, most of whom are asymptomatic, all sexually active teenagers should be screened. PMID- 2914242 TI - The year of living cautiously. PMID- 2914241 TI - Anemia causing cerebral infarction in a child. PMID- 2914243 TI - Family medicine departments not doing their job, rural MD asserts. PMID- 2914244 TI - Canada's health care legislation: good intentions, bad laws. PMID- 2914245 TI - After lean years group therapy making comeback, conference told. PMID- 2914246 TI - The doctor's office: poor design may cost you patients. PMID- 2914248 TI - Competence, evaluation and learning. PMID- 2914247 TI - There are some questions residency interviewers have no right to ask. PMID- 2914249 TI - Choosing interns: an exercise in frustration. PMID- 2914250 TI - Helping "heavy drinkers" recover. PMID- 2914251 TI - Insurance against medical misadventure? PMID- 2914252 TI - Abortion: defining right and wrong. PMID- 2914253 TI - Chronic fatigue syndrome. PMID- 2914254 TI - When is it time to quit? PMID- 2914255 TI - Amyloidosis associated with continuous ambulatory peritoneal dialysis. PMID- 2914256 TI - Capital punishment in Turkey. PMID- 2914257 TI - Glass is detectable on plain radiographs. PMID- 2914258 TI - Determining medical fitness to drive: physicians' responsibilities in Canada. AB - Current legislation indicates that physicians in Canada have a legal responsibility to know which medical conditions may impede driving ability, to detect these conditions in their patients and to discuss with their patients the implications of these conditions. The requirements to report unfit drivers vary among the provinces, and the interpretations of the law vary among the courts; therefore, physicians' risks of liability are unclear. Physicians may be sued by their patients if they fail to counsel the patients on the dangers of driving associated with certain medications or medical conditions. Physicians may also face legal action by victims of motor vehicle accidents caused by their patients if the court decides that the physicians could have foreseen the danger of their patients' continuing to drive. Physicians' legal responsibilities to report patients with certain medical conditions override their ethical responsibilities to keep patients' medical histories confidential. PMID- 2914259 TI - Efficacy of empirical cardiac pacing in syncope of unknown cause. AB - Cardiac pacing is often considered in patients with recurrent syncope after repeated attempts to document the cause have failed. To assess the results of this tactic we reviewed the records of 104 patients who had received pacemakers for known or suspected bradycardia between September 1973 and March 1985. The patients were classified retrospectively into three groups: group 1 (31 patients with a mean age of 73 years) had unequivocal documentation of bradycardia during syncope, group 2 (42 patients with a mean age of 71 years) had electrocardiographic or electrophysiologic evidence of potential bradycardia but no documentation during spontaneous syncope, and group 3 (31 patients with a mean age of 69 years) had a history "suggestive of" bradycardia-related syncope but no other evidence to support the diagnosis. The rates of recurrence of syncope during follow-up were 6.3%, 7.3% and 32.2% in groups 1, 2 and 3 respectively (p less than 0.01). In group 3 recurrence was more probable in patients with loss of consciousness for more than 2 minutes than in those who were unconscious for 2 minutes or less (p less than 0.05). The results suggest that pacemaker implantation is justified for recurrent syncope after extensive attempts to document a spell have failed if abnormal diagnostic test results suggest bradycardia as a possible cause. Empirical pacing is less satisfactory in patients with normal results of evaluation but may arguably be justified when patients have recurrent syncope with injury. PMID- 2914260 TI - Incidence of infantile hypertrophic pyloric stenosis in Saskatchewan, 1970-85. AB - We reviewed the incidence rates of infantile hypertrophic pyloric stenosis (IHPS) and pylorospasm in Saskatchewan from 1970 to 1985 and found a marked decrease in the rates after 1976. As expected, there was a preponderance of males among those with IHPS and among those with pylorospasm discharged from hospital between 1 and 3 months of age. No seasonal pattern was observed. We believe that the decrease in incidence rates was related to environmental influences, such as changes in the methods of feeding observed since 1977. PMID- 2914261 TI - Infantile hypertrophic pyloric stenosis: a study of feeding practices and other possible causes. AB - We carried out a case-control study of the hospital charts of 91 infants with infantile hypertrophic pyloric stenosis (IHPS) to determine the feeding practices at the time of discharge from the neonatal nursery. We excluded infants whose feeding might have been influenced by confounding factors. The infants were matched with controls for gestational age. The mean birth weight of the IHPS group was 3501 g and of the control group 3543 g. The male:female ratio for the IHPS group was 5.5. The odds ratio of male predominance was 4. We found that bottle-feeding was 2.9 times more prevalent among the infants with IHPS than among the control subjects. We speculate that the recently observed decrease in the incidence of IHPS is due to the decline in bottle-feeding. PMID- 2914262 TI - Primary lipoprotein-lipase-activity deficiency: clinical investigation of a French Canadian population. AB - We examined 56 French Canadians, aged 1 week to 54 years, from eastern Quebec who were referred to the Laval University Lipid Research Centre and in whom coincidental finding (in 46% of the cases), abdominal pain (in 32%) or family screening (in 22%) led to the diagnosis of primary lipoprotein-lipase-activity deficiency (familial hyperchylomicronemia). Half of the patients had one or more of the following signs: lipemia retinalis, eruptive xanthomas, splenomegaly and hepatomegaly; the plasma triglyceride concentrations were significantly higher (greater than 40 mmol/L) among these patients than among those without clinical signs (mean 21.7 [standard deviation 13.5] mmol/L). The prevalence rate of this disorder was 30 times higher than the previously published rate and was highest in the counties of Charlevoix and Saguenay-Lac-St-Jean (200 and 100 cases per million respectively) because of the distinct demographic history of these areas. Because of a founder effect an autosomal recessive gene involved in lipoprotein lipase expression or activation has probably been disseminated among this isolated French Canadian population. PMID- 2914263 TI - Coin rolling misdiagnosed as child abuse. PMID- 2914264 TI - Attempts to improve rail safety run head on into CMA concerns. PMID- 2914265 TI - Hopelessness and helplessness: treating the doctors who treat AIDS patients. PMID- 2914266 TI - What do women patients want? Tridont thinks it has the answer. PMID- 2914267 TI - Caring for Canada's VIPs. PMID- 2914268 TI - A long-term follow-up study of patients with gastric cancer detected by mass screening. AB - This report is based on 1,139 patients with gastric cancer (GC) detected by mass screening conducted by the Center for Adult Diseases, Osaka during 1961-1985. Early GC totalled 527 patients and advanced GC totalled 612 patients. In 859 patients curative resection was performed. Their vital status was traced yearly and six patients were lost to follow-up. Relative survival rates of screening detected GC patients were 69-70% and almost constant after 5 years from operation/diagnosis. The survival curve in which only death from GC was counted as a death was almost equal to the relative survival curve in its shape and value. The hazard rates of screening detected GC patients decreased rapidly within 7 years and remained low after 7 years. It was confirmed by this long-term follow-up study that about two thirds of GC patients detected by screening were successfully cured of their disease. PMID- 2914269 TI - Lung function following treatment of malignant tumors with surgery, radiotherapy, or cyclophosphamide in childhood. A follow-up study after 11 to 27 years. AB - A group of 40 individuals were restudied at a median follow-up time of 18 years after chest surgery, chest irradiation, or cyclophosphamide treatment. Their median age at diagnosis was 4.5 years. Nineteen subjects were operated on in the chest area. Radiotherapy of the chest had been used in 21 and cyclophosphamide in 35 patients. Chest deformity was evident in 17 subjects. Chest radiographs showed some evidence of fibrosis in eight subjects and late effects of surgery in three subjects. In nine subjects some evidence of fixed obstruction was seen in spirometry. In three subjects pulmonary diffusion capacity was abnormal. Spirometry commonly showed a restrictive pattern of findings. The incidence of abnormalities in pulmonary function was highest among the patients diagnosed before age 3 years. Spirometry was more likely to reveal abnormalities in patients who had received irradiation to the chest. However, abnormalities in pulmonary function were fewer than anticipated. PMID- 2914270 TI - Ifosfamide-induced renal tubular defects. AB - Unexpected nephrotoxicity has been described in high-dose, bolus ifosfamide (IFF) therapy. Renal injury is not thought to occur in patients receiving fractionated schedules, although microscopic hematuria from bladder irritation is not uncommon. IFF is undergoing trials in patients with malignant lymphomas, gynecologic malignancies, and advanced sarcomas and has shown promising results. This report describes renal abnormalities in four patients with malignant lymphoma receiving single-agent, fractionated IFF and suggests a proximal tubular defect in two patients who were studied in greater detail. These findings suggest an unreported and unique toxicity of IFF when given in smaller, fractionated doses. PMID- 2914271 TI - Interstitial brachytherapy for metastatic brain tumors. AB - Since December 1979, 14 patients with progressive metastatic brain lesions have been treated with temporary implantation of high-activity iodine 125 sources using stereotaxic techniques. Four patients had prior surgical resections, and 13 had been treated with external whole-brain radiotherapy. Nine patients had brachytherapy performed at recurrence 4 to 16 months after conventional radiation therapy; the other four had implants as an adjuvant "boost" to the tumor area from 2 to 4 weeks after external radiation. Six patients have since died: two with stable brain lesions at 4 and 22 weeks, respectively; three with progressive systemic and CNS tumors at 23, 24, and 29 weeks, respectively; and one with progressive CNS disease 116 weeks postimplant. The remaining eight patients are alive with a median follow-up of 63 weeks (range, 52-239+ weeks). Median survival for the entire group is 80 weeks. Brain tumor brachytherapy may be useful for palliation and possible long-term survival in selected patients with solitary metastatic disease. PMID- 2914272 TI - Ethylchlorformate polymerized tumor protein immunotherapy of the murine bladder tumor. AB - Using murine transplantable transitional cell carcinoma (MBT2), the effect of ethylchlorformate (ECF) polymerized tumor protein was compared with that of bacillus Calmette-Guerin (BCG). Seventy-five C3H/He mice were challenged with an intradermal inoculation of 5 X 10(5) viable MBT2 tumor cells and divided into five groups. Each group was intradermally administered with 0.01 mg of ECF (low ECF), 0.25 mg of ECF (high ECF), 0.1 mg of ECF and 10(6) CFU BCG (ECF/BCG), 10(6) CFU of BCG alone or normal saline (control) weekly for 10 weeks. The mean survival rate for the treatment groups was 64 to 73 days and significantly longer than that for the control group (P less than 0.001, Savage). The incidence of biologically active tumor progression was significantly less for the treatment groups (low ECF, 53%; high ECF, 33%; ECF/BCG, 7%; BCG, 27%) compared with the control group (87%; P less than 0.5, chi-square. The mean rate of tumor growth was significantly lower for all treatment groups than for the control group (P less than 0.001, ANOVA and SNK), and the ECF/BCG group had the lowest growth rate despite a higher incidence of local granulomatous reaction. In this study, immunotherapy significantly prolonged the survival rate, decreased the incidence of biologically active tumor progression, and slowed the rate of tumor growth. The combination of ECF polymerized tumor protein and BCG had the greatest effect, suggesting that the effect of the vaccine was increased with BCG. PMID- 2914273 TI - Establishment of tumor cell lines from a patient with head and neck cancer and their different sensitivities to anti-cancer agents. AB - The authors established five cell lines from a human head and neck tumor. The five cell lines (HC-2, HC-3, HC-4, HC-7, and HC-9) exhibited different sensitivities to Adriamycin, cisplatin, bleomycin, 5-fluorouracil, vincristine, and daunomycin. The D50 was 200 ng/ml Adriamycin (doxorubicin) for HC-7 and 45 ng/ml for HC-2. At the inception of long-term culture (11 months) in the absence of any drug, the sensitivity to Adriamycin of HC-7-5 (subcloned from HC-7) was 3.4 times greater than that of HC-2-6 (subcloned from HC-2); by 11 months, it decreased to 1.6 times that of HC-2-6. The cytocidal action of Adriamycin on HC-2 6 and HC-7-5 was potentiated when Adriamycin was combined with verapamil or cepharanthine. Cepharanthine also potentiated daunomycin and vincristine (VCR) against HC-2-6 and HC-7-5 cells, and it almost completely overcame drug resistance to daunomycin and vincristine in HC-7-5/VCR, a multidrug-resistant variant isolated after long exposure to vincristine of HC-7-5 cells in culture. The cellular accumulation of [3H]-daunomycin by HC-7-5 cells was about 70% that of HC-2-6 cells. By Northern blot analysis, using a multidrug-resistance gene (mdr-1) probe, neither HC-2-6 nor HC-7-5 expressed the mdr-1 gene, but HC-7-5/VCR or other multidrug-resistant variants showed active expression of the mdr-1 gene. Differential sensitivities among the five cell lines to 5-fluorouracil, cisplatinum, and bleomycin appear to be mediated through other mechanism beside the mdr-1 gene. PMID- 2914274 TI - Mesenchymal differentiation of cell lines obtained from human gliomas inoculated into nude mice. AB - Tumor formation in nude mice (nu/nu Balb c outbred) inoculated with cells from four new permanent human glioma cell lines was studied. Three of these lines had previously been shown to display features of striated muscle in vitro. Histochemical and immunochemical techniques together with electron microscopic study confirmed that striated muscle differentiation continued to be expressed in vivo. Two of the cell lines arguably showed greater striated muscle differentiation in vivo, whereas one has lost this ability. In one of the two, further mesodermal differentiation was evident with the formation of cartilage. PMID- 2914275 TI - Ability of a benign tumor to decrease spontaneous food intake and body weight in rats. AB - Malignant tumors induce anorexia and decrease spontaneous food intake and weight loss. Whether these effects are in part due to the tumor's physical size was investigated by inducing a benign cystic tumor mass with carrageenan in rats and then studying them for 21 days. Forty-two control rats were given subcutaneous injection of 3 ml of normal saline. Fifty-six study rats were given 3 ml of a 1.5% carrageenan solution subcutaneously, both in the right flank. Daily spontaneous food intake, body weight, and tumor weight were measured. Eight study and six control rats were randomly sacrificed on days 1, 3, 5, 7, 10, 14, and 21. Blood was obtained by cardiac puncture for albumin determination, and the tumor, carcass, liver, and spleen were removed and weighed. Tumor and tissue samples were histologically examined. All rats injected with carrageenan developed a benign cystic tumor mass. Early cystic wall consisted mainly of foamy macrophages with a light lymphoplasmacytic chronic inflammatory infiltrate and moderate vascularization. At day 21, cystic wall was more compact. The vasculature had collapsed and there were more pronounced fibroblastic response and collagen bundles. Average tumor weight by day 21 was 41 g. Average spontaneous food intake was depressed by about 15% from day 8 on in study rats as compared to controls. A significant decrease in carcass weight of 15.2% was observed in study as compared to control rats at day 21. Serum albumin was significantly decreased in study rats after day 5. Liver weight was significantly lower and spleen weight higher in study rats as compared to controls. These data suggest that some characteristics associated with cancer anorexia can be found in the absence of malignancy. PMID- 2914276 TI - Fine needle aspiration biopsy in the management of children and young adults with peripheral lymphadenopathy. AB - To determine the effectiveness of fine needle aspiration (FNA) of the lymph node in the management of young patients with peripheral lymphadenopathy, all patients 30 years of age and under who had a lymph node aspirate and who then had subsequent excisional biopsy, autopsy, or clinical follow-up for a minimum of one year were examined. One hundred twenty-seven aspirates from one hundred twenty six patients fulfilled the criteria of the study. Diagnoses of eighty-three benign and thirty-seven malignant lymphadenopathies were confirmed. There were three false negative and four false positive diagnoses. Sensitivity, specificity, and positive and negative predictive values were 0.93, 0.95, 0.90, and 0.97%, respectively. Of the one hundred twenty-six patients, twenty-five had a previous history of malignancy. Results of aspiration biopsy in this group were examined to determine FNA ability to predict recurrent disease. In this group the sensitivity, specificity and positive and negative predictive values were 0.95, 0.80, 0.95, and 0.80 respectively. Finally, the group of patients with clinically suspicious primary lymphadenopathy without an antecedent history of malignancy were examined to determine the effectiveness of the technique for selecting patients for surgical biopsy. This group included a total of one hundred two patients. Sensitivity, specificity, and positive and negative predictive values were 0.93, 0.96, 0.90, and 0.97, respectively. Based on the data from this retrospective study, we conclude that fine needle aspiration provides a useful tool in the management of young patients with peripheral lymphadenopathy, both in monitoring recurrent disease and in triaging patients with clinically suspicious primary lymphadenopathy to determined the next appropriate step in management. PMID- 2914277 TI - Mucoepidermoid tumors of the salivary glands. Correlation of cytophotometrical data and prognosis. AB - The mucoepidermoid tumors of the Salivary Gland Registry, Institute of Pathology, University of Hamburg, Western Germany, were evaluated retrospectively with regard to epidemiologic data, clinical follow-up, and cytophotometric data. Clinical data were obtained in 71 cases. Tissue from 46 cases was studied by single cell scanning cytophotometric analysis. Two thirds of the tumors were located in the major salivary glands, the parotid being the most common site, one third occurred in the minor salivary glands. The age range was from 6 to 81 years; peaks were observed in the fourth and seventh decades; the sex distribution was almost equal. By means of a single cell scanning cytophotometric device, a division into "diploid" and "atypical" patterns was possible. The clinical course was well correlated with these two groups, the atypical group showing generally an unfavorable course. Especially in poorly differentiated tumors, selection of clinically aggressive tumors was possible by their atypical DNA distribution pattern. Consequently, single cell DNA assessment can be a useful supplementary tool in the clinicopathologic and prognostic evaluation of mucoepidermoid tumors of the salivary glands. PMID- 2914278 TI - Sources of diagnostic error in fine needle aspiration of the thyroid. AB - Smears obtained from 795 patients with suspicious thyroid nodules by fine needle aspiration (FNA) of the thyroid gland were seen over a 5-year period at the UCLA Center for the Health Sciences. From 72 patients who underwent subsequent surgical excision of their nodules, inadequate or discrepant FNA diagnoses were noticed in 20 cases (27.8%). These errors could be attributed to inadequate material for diagnosis (n = 6), sampling errors (n = 2), and cytodiagnostic errors (n = 12). If the diagnosis of follicular neoplasm was treated as indeterminate for malignancy, the overall efficiency of FNA was 88.9%. All false negative diagnoses were related to procedure (i.e., inadequate smears or missed sampling of the lesion). The frequency of inadequate smears, in turn, was strongly related to the type of physician performing the aspiration. The frequency was highest among community-based clinicians (32.4%) and lowest among hospital-based cytopathologists (6.4%). With adequate sampling, the finding of 100% sensitivity in the diagnosis of malignant neoplasms by FNA cytology reaffirms its role as the procedure of choice in the initial screening of thyroid nodules. PMID- 2914279 TI - Use of the copper/zinc ratio in the diagnosis of lung cancer. AB - Serum zinc (Zn), copper (Cu), and the Cu/Zn ratio were evaluated in 84 patients with pulmonary lesions before surgery and in 100 healthy normal controls. There were 20 patients with benign and 64 with malignant lung tumors. Only the mean (+/ SD) Cu/Zn ratio was significantly higher in malignant tumors (2.24 +/- 0.78) than in benign tissue (1.63 +/- 0.33) (P less than 0.001). In the normal group, the Cu/Zn ratio was significantly lower (1.43 +/- 0.29). Patients with advanced disease (Stage III) had higher Cu/Zn ratio than patients in Stages I and II (2.65 +/- 0.86 versus 1.9 +/- 0.27) (P less than 0.001). At a cutoff value of 1.72, Cu/Zn ratio had a sensitivity of 89%, specificity of 84%, positive predictive value of 78%, and negative predictive value of 92% between controls and lung cancer patients. Between lung cancer patients and patients with benign pulmonary lesions the aforementioned values were 89%, 70%, 90%, and 70% respectively. A correlation between increasing Cu/Zn ratio and tumor extension and postoperative survival was observed. These findings suggest that Cu/Zn ratio may be used as a diagnostic test in lung cancer patients. PMID- 2914280 TI - Characterization of ovarian dysplasia by interactive morphometry. AB - This study defines, by morphometric analysis, criteria for the diagnosis of ovarian dysplasia. Areas of surface epithelium, adjacent to Stage I ovarian serous papillary adenocarcinoma, were diagnosed as dysplastic and evaluated for architectural and cytologic changes by means of two specially designed interactive morphometric procedures. Statistical evaluation was based on stepwise discriminant analysis of multiple quantitative descriptors. A data base was generated by analyzing histologic slides from eight normal (control), and 13 malignant ovarian tissues. Confirmation of the diagnosis was achieved in each case. The histologic criteria for ovarian dysplasia differ from those used for ovarian borderline malignancy. Interactive morphometric image analysis offers an objective method for delineating cancer precursors that could be used in ovarian biopsies taken by laparoscopy or during incidental abdominal surgery. It could be applied to cancer precursors in other locations. PMID- 2914281 TI - Failure of preoperative staging to assess unresectability in M0 bronchogenic carcinoma. AB - Despite extensive preoperative staging, unresectability of a bronchogenic carcinoma may not be known until an exploratory thoracotomy is done. Failures in anatomic staging occur because of inability to detect local extent of hilar lesions and inability to detect small deposits of metastatic disease. At the University of South Carolina, nine of 75 patients who underwent thoracotomies were found to be unresectable. Using an extensive staging protocol, the "back out" thoracotomy rate can be reduced to a minimum whereas no patient is denied a chance for surgical cure. PMID- 2914282 TI - Reactive changes in the esophageal epithelium and predictability of survival for patients with adenocarcinoma of the upper third of the stomach. AB - In 93 patients with an adenocarcinoma in the upper third of the stomach and involving the lower esophagus, the authors examined the histopathologic changes of the esophageal epithelium at the involved lesion, and the prognosis. Changes in the esophageal epithelium were histologically divided into four groups: hyperplastic (34 cases), atrophic (26 cases), hyperplastic and atrophic (mixed, 20 cases), and no change (13 cases) types. The hyperplastic type was closely related with the expanding mode of invasion and depth of the invasion was less than seen with the atrophic type (P less than 0.05). The rate was significantly higher in cases of a curative resection and the outcome was better than seen with the other types (P less than 0.01-0.001). The atrophic type was related with Borrmann type IV of the gross type and infiltrative mode of invasion, and had a significantly longer length of esophageal invasion than did the hyperplastic and the no change types (P less than 0.01). The prognosis was significantly poorer than seen with the hyperplastic (P less than 0.001) or the mixed types (P less than 0.01). Our study shows that histopathologic changes in the esophageal epithelium provide the surgeon with useful prognostic indicators in cases of an adenocarcinoma in the upper third of the stomach and involving the lower esophagus. PMID- 2914283 TI - Chest wall tumors in infancy and childhood. AB - The chest wall is an infrequent site of malignancy in infancy and childhood. Management of these tumors, however, is of particular concern because of their aggressive behavior and the functional impairment which may result from local treatment. From 1976 to 1987 we have treated seventeen infants and children with tumors of the chest wall. Askin's tumors and Ewing's sarcoma were considered as a single entity, malignant small round cell tumor (MSRCT), and account for the majority (11 of the 17 patients). Other tumors represented were infantile fibrosarcoma (1), undifferentiated spindle cell sarcomas (2), osteogenic sarcoma (1), large cell lymphoma (1), and synovial sarcoma (1). Nine of 17 patients have survived (median follow-up of survivors 5 years); six patients died of disease and two from complications of therapy. All four patients with MSRCT and metastasis at diagnosis died of disease despite chemotherapy and radiotherapy. Four of the seven patients with localized MSRCT, who received combined modality therapy including resection (two after initial chemotherapy), radiotherapy, and chemotherapy, were continuously disease-free 16 months to 10 years following diagnosis. One of the three patients who failed died of complications of surgery to her extensive primary. A second patient had a relapse of disease in a hilar node four years after finishing vincristine, actinomycin, and cytoxan (VAC) chemotherapy; she was retreated with Adriamycin (doxorubicin, Adria Laboratories, Columbus, Ohio), vincristine, and cyclophosphamide as well as radiotherapy to her hilum and remains in second remission 56 months following her recurrence. The third patient suffered a distant relapse in bone and, before succumbing to his MSRCT, developed acute monocytic leukemia and died during a remission induction attempt. Mixed results were obtained for the patients with other tumor types. PMID- 2914284 TI - Esophageal squamous cell carcinoma associated with gastric adenocarcinoma. AB - Adenocarcinoma of the stomach occurred in six of 425 consecutive patients with esophageal squamous cell cancer. In two cases, the gastric cancer, which was recognized at 17 and 29 months, respectively, after the nonsurgical treatment of the esophageal tumor, was treated by surgical resection. In three cases, the tumors which were diagnosed simultaneously, were treated by surgery (one case) resection of the gastric tumor and nonsurgical therapy for the esophageal tumor (one case), and nonsurgical therapy for both tumors (one case). In one case, a gastric cancer was resected 6 years before diagnosis of an esophageal tumor and a second cancer in the gastric stump. A nonsurgical protocol was then adopted for both tumors. The association of these two cancers raises questions concerning their epidemiology, diagnosis, prognosis, and management. There is room for nonsurgical multimodality protocols and, in association with surgery, survival was prolonged for more than 1 year in five of six patients. PMID- 2914285 TI - Gastric cancer heterogeneity. AB - This study was carried out on 222 samples from 37 gastric carcinomas to assess the incidence of multiple stem lines in primary tumors and metastasis as reflected by multiple DNA stem lines and their relationship to epidermal growth factor (EGF) receptor expression, histologic grade, tumor size, and degree of wall infiltration. Fifteen primary tumors (40.5%) were homogeneously diploid/peridiploid whereas 22 (59.5%) were aneuploid. In the lymph node metastasis, seven patients (29.2%) had an homogeneous diploid/peridiploid pattern in all metastatic lymph nodes. On the other hand, 17 (70.8%) had at least one aneuploid peak in the lymph node metastasis. DNA content heterogeneity was seen in 12 (33%) of primary tumors whereas 14 (66.6%) of 21 patients had multiple cell clones in the metastasis. Therefore, 12 patients had a metastatic clone which was not observed in the primary tumor. DNA content heterogeneity was seen even in tumors with submucosal invasion suggesting that this phenomenon is also present at earlier stages. No correlation between the histologic grade and the DNA distribution was observed. Furthermore, histologic heterogeneity was independent of DNA content heterogeneity. The EGF receptor expression was observed in six of the 23 patients in whom this analysis was done. The EGF receptor expression was constant in all samples which were studied and even samples with a different DNA content and histologic grade were stables for the EGF receptor expression. PMID- 2914286 TI - Dedifferentiated parosteal osteosarcoma of the femur with aneuploidy and lung metastases. AB - In this report, the pathologic findings and the results of cellular DNA measurements of a tumor that on first presentation seemed to be a classical parosteal osteosarcoma are described. After resection 8 months later, part of the tumor appeared to display highly malignant features. DNA flow cytometry of this part of the tumor showed an aneuploid cell population. The aggressive nature of the tumor was confirmed by the development of lung metastases approximately 1 year after resection of the primary tumor. PMID- 2914288 TI - Etoposide admixed with cisplatin. Phase I clinical investigation of 72-hour infusion. AB - The compatibility of etoposide (VP-16-213) and cisplatin (CDDP) in an admixture solution was established by High Pressure Liquid Chromatography (HPLC) studies in vitro at room temperature. A Phase I dual-dose escalation study of the admixture was subsequently carried out utilizing a 24-hour continuous infusion schedule administered for 3 consecutive days and repeated at 3 to 4 week intervals. Twenty seven patients received a total of 42 treatment courses. The daily dose rates for VP-16-213 were 50, 75, and 100 mg/m2/day. Cisplatin was delivered at 20, 30, and 40 mg/m2/day for each dose level of VP-16-213. Dose-rate limiting toxicity was observed first at the VP-16 dose of 50 mg/m2/day and CDDP at 30 mg/m2/day. At 100 mg/m2/day for VP-16-213, six of 17 courses were associated with life-threatening leukopenia and four of six patients died with sepsis. All but one of the patients developing severe or life-threatening leukopenia had associated acute renal failure with serum creatinine levels greater than 2 mg/dl. The optimal dose rate of delivery for VP-16 and CDDP administered as a 72-hour infusion admixture is 75 mg/m2/day and 30 mg/m2/day, respectively. PMID- 2914287 TI - Phase II study of low-dose continuous infusion homoharringtonine in refractory acute myelogenous leukemia. AB - Thirty-one patients with a diagnosis of refractory acute myelogenous leukemia received homoharringtonine as their first (15 patients) or second (16 patients) salvage therapy. Homoharringtonine was given as a continuous infusion of 2.5 mg/m2 daily for 15 to 21 days to 13 patients (schedule 1), and of 3.0 mg/m2 daily for 15 days in 18 patients (schedule 2). Overall, one patient achieved complete remission (3%), and three (10%) had a hematologic improvement with normalization of the marrow and peripheral blood picture except for persistent thrombocytopenia. Six patients (19%) demonstrated prolonged myelosuppression, three (23%) on schedule 1 and three (17%) on schedule 2. Cardiovascular complications were minimal consisting of hypotension in one patient (3%) and supraventricular arrhythmias in two patients (6%). Hyperglycemia was observed in 42% of patients and was significant in 10%. The authors conclude that homoharringtonine, at the dose schedule investigated, has definite but low antileukemic efficacy. The low-dose continuous infusion schedule was associated with prolonged myelosuppression but no serious cardiovascular complications. The role of such therapy in myeloproliferative disorders, especially chronic myelogenous leukemia, deserves consideration. PMID- 2914289 TI - Cyclophosphamide, methotrexate, and 5-fluorouracil in a three-drug admixture. Phase I trial of 14-day continuous ambulatory infusion. AB - The compatibility and stability at room temperature for up to 7 days of a three drug admixture of cyclophosphamide, methotrexate, and 5-fluorouracil (5-FU) (CMF) was established permitting the practical delivery of the combination as an infusion in an ambulatory setting. Fourteen patients received 20 courses of CMF administered on a continuous infusion schedule for 14 days of a 28-day cycle. The dose rates were fixed for 5-FU (300 mg/M2/day) and methotrexate (0.75 mg/M2/day). The cyclophosphamide dose was escalated from 25 to 50, 75, and 100 mg/M2/d. Leukopenia and thrombocytopenia were observed in two of five patients receiving the maximal dose of cyclophosphamide. No other toxicities were observed including alopecia, stomatitis or liver function abnormalities. This Phase I trial suggests that the cumulative doses of cyclophosphamide, methotrexate, and 5-FU are comparable to the maximum doses delivered as single agent infusions. Furthermore, when the infusion CMF is compared to the "standard" bolus schedule for CMF, the infusion schedule delivers 116%, 8%, and 350% of the respective three component drugs (cyclophosphamide, methotrexate, and 5-FU). PMID- 2914290 TI - The role of serum CEA as a prognostic indicator in stage II and III breast cancer patients treated with adjuvant chemotherapy. AB - Carcinoembryonic antigen (CEA) values in 529 patients treated in two consecutive adjuvant chemotherapy protocols were analyzed to determine if CEA values correlated with disease-free status or prognostic utility. CEA values were evaluated preoperatively, before chemotherapy, at the conclusion of chemotherapy, and during postchemotherapy followup. The sensitivity of CEA for predicting disease recurrence was low; however, any abnormal CEA at the conclusion of chemotherapy and during followup significantly correlated with reduced disease free and overall survival. A CEA value greater than or equal to 20 ng/ml at the end of chemotherapy or during followup was highly specific and a strongly positive predictor for the presence of metastases. Abnormal CEA values before chemotherapy that became normal at the conclusion of chemotherapy were associated with a significantly reduced recurrence rate. An abnormal CEA value obtained before or after adjuvant chemotherapy is clinically useful and can provide prognostic information. PMID- 2914291 TI - Results of chemotherapy in advanced carcinoma of the fallopian tube. AB - Forty-six patients with measurable disease received chemotherapy for advanced primary or recurrent carcinoma of the fallopian tube. The response rate was 9% with single-agent therapy, 29% with multiagent therapy without cisplatin, and 81% with cisplatin-containing combination therapy. Survival was significantly improved in Stage III/IV with the addition of cisplatin-based combination therapy. PMID- 2914292 TI - Systemic doxorubicin and intraarterial cisplatin preoperative chemotherapy plus postoperative adjuvant chemotherapy in patients with osteosarcoma. AB - The role of adjuvant chemotherapy for osteosarcoma has been well defined. Recently, the use of preoperative chemotherapy has been further enhanced by the use of intraarterial cisplatin. The authors describe the use and results of systemic doxorubicin and intraarterial cisplatin as a preoperative regimen for eight pediatric patients with nonmetastatic osteosarcoma of an extremity. The therapy was well tolerated. Six patients achieved satisfactory local tumor control and were able to receive the surgical procedure to permit limb salvage. Two of these six patients subsequently developed metastatic disease. Of the two patients who did not achieve satisfactory local tumor control to permit a limb salvage procedure, both underwent amputation and one later developed metastatic disease. Five patients have remained continuously free of disease for a median of 18 months (range, 12-21 months). This report confirms the observations that intraarterial cisplatin and doxorubicin can be used as a safe and effective regimen preoperatively for pediatric patients with osteosarcoma of an extremity. PMID- 2914293 TI - Radiation therapy in stage II carcinoma of the endometrium. AB - A retrospective analysis of 61 patients with Stage II carcinoma of the endometrium was carried out. Our results suggest that when given carefully and adequately, radiation therapy alone is as effective as a combination of surgery and irradiation and is well tolerated. Five-year actuarial survival was 74.5% in patients treated with radiation therapy alone (16 patients) as compared to those patients who received either preoperative radiation (35 patients) or postoperation radiation (ten patients) where the survival was 70.8% and 78.3%, respectively (P greater than or equal to 0.05). Tumor was controlled in the pelvis in 93.4% of patients. Complications of treatment were seen in 8.2%. With the exception of one patient with bowel obstruction requiring surgery, the rest of the complications were minor. From these results, it appears that a planned radiotherapy is a good alternative to combination of surgery and irradiation. PMID- 2914294 TI - Immunophenotypic spectrum of plasma cell leukemia. AB - Four cases of plasma cell leukemia (PCL) are reported that illustrate the variable immunotype of this disorder in contrast with the immunologic profile described for normal B-cell maturation and typical multiple myeloma (MM). Mature B-lymphocytes express B1 antigen (Ag) and surface immunoglobulin (SIg) whereas maturation to the plasma cell stage is accompanied by loss of these immunologic markers and expression of T10 Ag, plasma cell Ag (PCA), and cytoplasmic immunoglobulin (CIg). Plasma cells from patients with MM have previously been found to express the immunophenotype of normal plasma cells. In contrast, none of the four cases reported here express an immunologic profile typical for specific B-cell differentiation stages. Only one of four cases was strongly positive for PCA but additionally expressed B1 Ag and SIg. Of the remaining three cases, all expressed T10 Ag and CIg; two cases also expressed SIg, weak PCA, and B1 Ag. All four cases were monoclonal for lambda light chains and negative for common ALL Ag (CALLA). The variable expression of mature B-cell markers and plasma cell markers demonstrates the immunophenotypic spectrum of PCL; the prognostic significance of this heterogeneity needs to be more closely examined. PMID- 2914295 TI - Porokeratosis as a premalignant condition of the skin. Cytologic demonstration of abnormal DNA ploidy in cells of the epidermis. AB - Clinical evidence has accumulated of malignant epithelial tumors developing on the lesions of porokeratosis. To determine the cytologic basis for the malignant change of porokeratosis, the nuclear DNA content of epidermal cells from porokeratotic lesions was measured using microfluorometry. A total of 42% of 33 porokeratotic skin lesions in eight of the 16 patients showed DNA polyploidization in the epidermis. Most of the porokeratotic skin lesions, with or without DNA polyploidization, increase cell proportions in the S and G2/M phase range. DNA indices of cells from these porokeratotic lesions distributed widely from the level of normal control epidermis to that of malignant epidermal conditions. These findings suggest that porokeratosis is undergoing the neoplastic process, and is a precursor of malignant tumors. PMID- 2914297 TI - The WHO histological classification of thyroid tumors: a commentary on the second edition. AB - This article introduces the revised WHO classification of thyroid tumors, giving an account of the major changes made and the reasons behind the changes, as well as listing the actual classification now recommended. It is intended to draw general attention to the revision, the full version of which will be published separately. PMID- 2914296 TI - Effects of sodium ascorbate (vitamin C) and 2-methyl-1,4-naphthoquinone (vitamin K3) treatment on human tumor cell growth in vitro. I. Synergism of combined vitamin C and K3 action. AB - The effects of sodium ascorbate (vitamin C) and 2-methyl-1,4-naphthoquinone (vitamin K3) administered separately or in combination on the in vitro cultured human neoplastic cell lines MCF-7 (breast carcinoma), KB (oral epidermoid carcinoma), and AN3-CA (endometrial adenocarcinoma) have been examined. When given separately, vitamin C or K3 had a growth inhibiting action only at high concentrations (5.10(3) mumol/1 and 10(5) nmol/l, respectively). Combined administration of both vitamins demonstrated a synergistic inhibition of cell growth at 10 to 50 times lower concentrations. At this level separately given vitamins are not toxic. The sensitivity to this treatment was somewhat different in the three cell lines, being slightly higher for KB line. This tumor cell growth inhibitory effect was completely suppressed by the addition of catalase to the culture medium containing vitamins C and K3, suggesting an excessive production of hydrogen peroxide as being implied in mechanisms responsible for the above-mentioned effects. PMID- 2914298 TI - Diagnostic accuracy of sialic acid in the diagnosis of malignant ascites. AB - The authors evaluated the diagnostic accuracy of sialic acid and its lipid-bound fraction in ascites and compared these tests with others (fibronectin, cholesterol) recently claimed as valuable in the differential diagnosis of ascites. Fibronectin yielded the best diagnostic accuracy (85%) with no false positive and 37% of false-negative (10/27). The authors also found higher concentration of sialic acid in malignant ascites than in nonmalignant ascites (P less than 0.001) and, taking 300 mg/l as the cutoff value, the false-positive rate was 10% (four of 40), the false-negative rate 30% (eight of 27), and the overall diagnostic accuracy 82%, comparable to that of the fibronectin. The authors conclude that both fibronectin and sialic acid determinations in ascites may be regarded as accurate markers of neoplastic involvement of the peritoneum, although no test is useful in the ascites with hepatocellular carcinoma and cirrhosis of the liver. PMID- 2914299 TI - Patterns of metastasis in uterine sarcoma. An autopsy study. AB - The autopsy findings of 73 patients with uterine sarcoma were studied to determine the sites and possible modes of metastasis. Homologous mixed mesodermal tumors were the most frequent (41%) followed by leiomyosarcoma (26%), heterologous mixed mesodermal tumor (18.3%), stromal sarcoma (12%), and endolymphatic stromal myosis (3%). The peritoneal cavity and omentum were the most frequently involved sites (59%), followed by the lung (52%), pelvic lymph nodes (41%), paraaortic lymph nodes (38%), and liver parenchyma (34%). The presence of lung metastasis was not associated with pelvic or paraaortic node metastasis or intraperitoneal disease. Metastasis to other distant sites including the brain, heart, kidney, and bone were independent of pelvic and paraaortic nodal metastasis or intraperitoneal disease. Metastatic sites were not different among various histologic types. Distant metastatic sites were statistically associated with lung metastasis. Hematogenous metastasis best explains this metastatic pattern and adjuvant systemic therapy seems indicated. PMID- 2914300 TI - Prognostic factors in the diagnosis and treatment of primary central nervous system lymphoma. AB - The authors describe the results of multimodality therapy in 27 patients with biopsy-proven primary central nervous system (CNS) lymphoma treated between 1976 and 1986. Treatment included surgical resection (15 patients), radiotherapy (27 patients), and chemotherapy (nine patients). Actuarial survival rates for the 27 patients at 1, 2, and 5 years after diagnosis were 70%, 54%, and 45%, respectively. Nine patients were recurrence-free at 8 to 106 months follow-up. A multivariate risk analysis identified five factors which had a favorable impact on survival: (1) age less than 60 years (P less than 0.02); (2) preoperative Karnofsky performance score greater than or equal to 70 (P less than 0.02); (3) presence of strictly hemispheric tumor (P less than 0.0003); (4) whole-brain radiation dose between 4000 and 5000 cGy (P less than 0.05); and (5) addition of chemotherapy to radiotherapy (P less than 0.002). Patients with complete tumor resolution on computed tomography 6 months after beginning treatment also had longer survival (P less than 0.01). The presence of malignant cells on cerebrospinal fluid cytologic examination correlated with an increased risk of distant metastasis (P less than 0.05). In those patients whose disease eventually recurred, the administration of an additional therapeutic modality significantly increased the length of postrecurrence survival (P less than 0.05). Although surgical resection provided no increase in survival, the addition of chemotherapy to postoperative cranial irradiation significantly enhanced the duration of survival. Our experience suggests that pretreatment clinical and diagnostic factors can help in predicting survival and in planning treatment. PMID- 2914301 TI - Influence of exogenous estrogens, proliferative breast disease, and other variables on breast cancer risk. AB - The authors reevaluated 10,366 consecutive breast biopsy specimens of benign lesions performed between 1950 and 1968. Follow-up information was obtained on 3303 women with a median duration of follow-up of 17 years. This sample contained 84% of the patients originally selected for follow-up. The relative risk (RR) of developing breast cancer was 0.98 for women who took exogenous estrogens as compared to 1.8 for women who did not. Exogenous estrogens lowered the observed breast cancer risk in women with atypical hyperplasia (RR = 3.0 versus 4.5), proliferative disease without atypia (RR = 0.92 versus 1.9), and in women without proliferative disease (RR = 0.69 versus 0.91). Women who took estrogens before 1956 were at 2.3 times the risk of other estrogen users, presumably due to a dose effect. There was no significant association between breast cancer risk and birth control pills, cigarette smoking, or alcohol consumption. Exogenous estrogens are not associated with increased breast cancer risk in women with benign breast disease. A previous history of benign breast disease does not contraindicate replacement estrogen therapy. PMID- 2914302 TI - Breast cancer in aging women. A population-based study of contrasts in stage, surgery, and survival. AB - Over 43% of the newly diagnosed breast cancers in the US occur in women 65 years or older. Yet little attention is devoted to the age-associated aspects of this malignancy. This study uses data on more than 125,000 women diagnosed from 1973 to 1984 to examine the influence of advancing age on breast cancer. The National Cancer Institute's Surveillance, Epidemiology, and End Results Program provides information on disease stage, surgery, histologic type, and survival time to compare and contrast women in all age groups. Women who present initially with distant disease are more likely to be elderly. Certain surgical procedures are used less frequently for older women. No unusual age variations in histologic features are noted. Elderly women do as well as younger patients in survival time for localized and regional stages of breast cancer; for distant disease, they fare worse. Results emphasize the need to focus on elderly women for screening, early detection, diagnostic evaluation, and therapy. PMID- 2914303 TI - Contribution of socioeconomic status to black/white differences in cancer incidence. AB - Blacks and Whites have very different cancer incidence rates for many sites, but this may largely be due to the racial differences in socioeconomic status (SES). The authors tested this hypothesis by determining the effect of adjustment for SES on the black/white incidence ratios for 12 cancer sites. Race-specific census tract-level SES variables (median family income, percent below poverty level, and years of education) were obtained from the 1980 US census and applied to approximately 20,000 black and 88,000 white cancer cases from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program for the years 1978 to 1982. For each cancer site (with each sex considered separately), Poisson regression was used to produce age-adjusted black/white incidence ratios, with and without adjustment for SES. The SES variable with the strongest adjusting power was percent below poverty level. For many sites (breast, in situ and invasive cervix, esophagus, male lung, pancreas, stomach) poverty accounted for much or all of the racial differences. For several sites (bladder, multiple myeloma, prostate, uterine corpus), large racial differences persisted after adjustment for poverty, and these findings suggest directions for investigating the etiology of these cancers. PMID- 2914305 TI - Caring for colleagues. PMID- 2914304 TI - Long-term follow-up of parental adjustment following a child's death at home or hospital. AB - The adjustment of parents whose children had died from cancer 6 to 8 years earlier was assessed using structured interviews and standardized inventories. Forty parents had participated in a home hospice program during the terminal phase of their child's illness whereas 22 were parents of children who died in the hospital. Home care parents reported significantly stronger relationships with spouse and remaining children, firmer religious convictions, more adequate coping abilities, and less residual guilt than non-home care parents. On the Minnesota Multiphasic Personality Inventory (MMPI), non-home care parents exhibited more frequent indications of maladjustment including somatization, depression, and interpersonal problems. The results confirm that the more optimal adjustment of home care parents which was first reported 5 years earlier has been maintained. Support and expansion of pediatric home hospice programs are strongly encouraged in light of the positive results of our longitudinal studies. PMID- 2914306 TI - Caribou bones and labrador tea. PMID- 2914307 TI - Learning from Mark. PMID- 2914308 TI - The birth control clinic. PMID- 2914310 TI - Baccalaureates for RNs. PMID- 2914309 TI - Write right. PMID- 2914311 TI - [Facing AIDS in Zambia]. AB - An alternative approach to AIDS in Zambia. Zambians have lived with what we now call AIDS for 20 years. Today, an estimated eight percent of newborns are infected with the virus. Yet dealing with AIDS in this traditional society is an onerous task. While the country's 10,000 nurses are educated in the ways of modern medicine, they are matched by an equal number of traditional healers. And it is traditional values that Zambians turn to when faced by diseases for which modern medicine has few answers--diseases like cancer and AIDS. This author, a nurse educator with The Missionary Sisters of Our Lady of Africa, challenges young nurses to help Zambians respond effectively to this complex situation. PMID- 2914313 TI - Heart disease in women. PMID- 2914312 TI - [The dreams of the young are dashed against reality]. AB - The dreams of the young collide with reality. In their professional trends class, third year nursing students at Algonquin College in Ottawa studied proposals from the College of Nurses of Ontario (CNO), the licencing body in that province. For example, the College is considering the development of a third level of nurse beyond the RNA and RN: a nurse specialized in advanced practice. The students expressed their concerns about the proposals in this letter to the College. PMID- 2914314 TI - Intercoronary and intracoronary communications in four cases of vasospastic angina. AB - Persistent intercoronary and intracoronary communications were observed on cineangiograms in four patients having vasospastic angina without significant coronary narrowings. On provocation of coronary spasm using ergonovine maleate, these communications seemed to protect myocardium from ischemia, at least partially. PMID- 2914315 TI - Mitral valve rupture during percutaneous dilation of aortic valve stenosis. AB - A 62-year-old patient underwent catheter balloon valvuloplasty for aortic valve stenosis. During the procedure, iatrogenic severe mitral regurgitation was induced, requiring emergency surgery. At operation, extensive laceration of the septal mitral leaflet was found; chordae tendinae were intact. Retrospective examination of the cineangiogram revealed the presence of balloon indentation at the chordal level during inflation, which disappeared at full inflation. Mitral valve rupture was probably related to balloon entrapment in chordae tendinae, severe chordal stretching at inflation, and subsequent valve laceration. This severe complication or aortic valvuloplasty in adults has not been reported previously and probably could be avoided by careful observation of guidewire and balloon position before inflation. PMID- 2914316 TI - Fatal aortic rupture: an unusual complication of percutaneous balloon valvuloplasty for acquired valvular aortic stenosis. AB - A case report complicated by a perforation of the ascending aorta during percutaneous balloon valvuloplasty for acquired aortic stenosis in a bicuspid aortic valve is presented. The clinical and pathological findings are discussed. It is suggested that in patients with hard calcified valve cusps and calcifications of the aortic annulus balloon sizes exceeding the aortic diameter should be avoided. PMID- 2914317 TI - Aortic annular tear after valvuloplasty: the role of aortic annulus echocardiographic measurement. AB - Following percutaneous transluminal aortic valvuloplasty, 2/100 patients (2%) developed significant aortic insufficiency as a result of an aortic annular tear. Both patients underwent emergency aortic valve replacement and survived the operation. One patient died 4 weeks postoperatively from sepsis and multiorgan failure, and the other patient had a benign postoperative course. In both cases, the balloon area significantly exceeded the aortic annular area and caused the complication. Review of the balloon area-aortic annular area ratio in our series showed that a value of less than 1.2 was not associated with this complication. PMID- 2914318 TI - Severe aortic regurgitation complicating percutaneous aortic valve valvuloplasty. AB - An 88-year-old patient undergoing percutaneous aortic balloon valvuloplasty of a tricuspid aortic valve is described. The patient had mild aortic regurgitation prior to the procedure but developed severe aortic regurgitation after balloon dilatation of the valve. At the time of surgery there was no anatomic disruption of the valve or supporting structures. Development of severe aortic incompetence following balloon valvuloplasty has not been previously reported. PMID- 2914319 TI - "Banding" of the pulmonary artery with an inflated Swan-Ganz catheter in a patient with postinfarction ventricular septal rupture. PMID- 2914320 TI - Successful permanent pacing via a unilateral left sided superior vena cava. PMID- 2914321 TI - Thromboembolic complications in coronary angiography associated with the use of nonionic contrast medium. PMID- 2914322 TI - Left heart catheterization by direct ventricular puncture: withstanding the test of time. AB - If retrograde arterial catheterization of the left ventricle fails because of a stenosed native or tissue valve or is contraindicated because of the presence of a mechanical aortic prosthesis, then alternative routes of access to the left ventricle are either transseptal or direct (transapical) left ventricular puncture. The transseptal approach is contraindicated in the presence of a mechanical mitral valve prosthesis. Under these circumstances we have used direct transapical left ventricular puncture in the treatment of 112 patients and have found this technique to be successful with little associated risk. A major complication occurred in 3% of the patients, but the study provided the required data in 95%, and these figures compare favorably with the reported results of transseptal catheterization. PMID- 2914323 TI - Angina and vasospasm at rest in a patient with an anomalous left coronary system. AB - An anomalous left main coronary artery with passage between the right ventricular infundibulum and aortic root has been incriminated as the causation of sudden death in a small number of individuals, many of whom are quite young. Mechanical features such as angulation and compression are most often incriminated. A 59 year-old man with such a coronary anomaly who had chest pain at rest, ST segment elevation, and ventricular tachycardia, but who had no evidence of effort-related myocardial ischemia, is reported. Improvement in the degree of coronary tone in the anomalous left main coronary with intracoronary nitroglycerin administration was demonstrated. This represents the first report of an individual with an anomalous left main coronary system with ventricular tachycardia/ventricular fibrillation and documented vasospasm in the anomalous artery. PMID- 2914324 TI - Biased hypermutation of viral RNA genomes could be due to unwinding/modification of double-stranded RNA. PMID- 2914326 TI - Nursing in the public sector: views from two public health nursing leaders. PMID- 2914325 TI - Major nucleolar proteins shuttle between nucleus and cytoplasm. AB - Nucleolin is a 92 kd nucleolar protein implicated in regulating polymerase I transcription and binding of preribosomal RNA. Another abundant nucleolar protein of 38 kd (B23/No38) is thought to be involved in intranuclear packaging of preribosomal particles. Although both proteins have previously been detected only in nuclei, we conclude that they shuttle constantly between nucleus and cytoplasm. This conclusion is based on monitoring the equilibration of these proteins between nuclei present in interspecies heterokaryons, and on observing the antigen-mediated nuclear accumulation of cytoplasmically injected antibodies. Our unexpected results suggest a role for these major nucleolar proteins in the nucleocytoplasmic transport of ribosomal components. Moreover, they suggest that transient exposure of shuttling proteins to the cytoplasm may provide a mechanism for cytoplasmic regulation of nuclear activities. PMID- 2914327 TI - Clinical indicators of the ability to sustain spontaneous ventilation: a pilot study. PMID- 2914328 TI - Effect of the glutathione S-transferase inhibitor, tienilic acid, on biliary excretion of sulphobromophthalein. AB - Tienilic acid, a phenoxyacetic acid diuretic, reduces the amount of total sulphobromophthalein (BSP) excretion in the isolated perfused rat liver (IPRL). This reduction was primarily by reduction in excretion of conjugated BSP, with excretion of unchanged BSP being relatively unaffected. TA also reduces the amount of conjugated BSP formed in vitro, indicating that its effect in the IPRL may be by means of inhibiting the glutathione S-transferase enzymes involved in the formation of the conjugate. It would appear that a reduction in the biliary excretion of BSP cannot be taken to be an indication of reduced liver function in a general sense. PMID- 2914329 TI - Metabolism of selectively methylated and deuterated analogs of 1,2-dibromo-3 chloropropane: role in organ toxicity and mutagenicity. AB - In vitro bromide release and in vivo glutathione (GSH) depletion in rat liver, kidney and testis by 1,2-dibromo-3-chloropropane (DBCP) and selectively methylated and deuterated DBCP analogs were studied. With liver microsomes from phenobarbital-pretreated rats the bromide release from the C1-C3-D4- and the perdeuterated DBCP analogs were 54% and 26% of that of DBCP, respectively. Inhibitors of P-450 reduced the bromide release to 10-20% of that without additions. This correlated with the effects of deuterium substitution and additions of P-450 inhibitors on DBCP-induced bacterial mutagenicity as reported elsewhere by this laboratory. To study the importance of GSH-dependent metabolism in DBCP toxicity, bromide release was assayed in cytosolic preparations using methylated analogs of DBCP. With the C1-methyl-derivative, bromide release was markedly reduced compared to that with DBCP in cytosols from liver, kidney and testis. A similar reduction in in vivo nephrotoxicity and testicular damage has recently been reported. The obtained correlation between in vitro GSH-dependent metabolism of methylated DBCP analogs and their in vivo organ damaging potential, points to an involvement of GSH-dependent metabolism in DBCP-induced in vivo toxicity. Both DBCP and the methylated analogs (360 mumol/kg i.p.) depleted the GSH levels in liver after 1 and 3 h and in kidney after 1 h, whereas in the testis no significant depletion of GSH was obtained. As kidney and testis are reported to be the primary target organs for DBCP, there was an apparent lack of correlation between tissue depletion of GSH and organ toxicity. PMID- 2914330 TI - Studies on the mechanism of reduction of azo dye carcinogens by rat liver microsomal cytochrome P-450. AB - This laboratory has described the azoreduction of p-dimethylaminoazobenzene (1c) by rat liver microsomal cytochrome P-450. To elucidate the mechanisms involved, the reduction of structurally related azobenzenes by hepatic microsomes was investigated. High substrate reactivity was observed for 1c, its corresponding secondary (1a) and primary (1b) amines and p-hydroxyazobenzene (1d). In contrast, only negligible rates were obtained for unsubstituted azobenzene (1g), hydrazobenzene (2g), p-isopropylazobenzene (1e) and 1f, the benzoylamide derivative of 1b. These results clearly indicate that electron-donating groups, such as hydroxyl or primary, secondary and tertiary amines, are essential for binding of azo dye carcinogens to liver microsomal cytochrome P-450 and, by implication, their enzymic reduction. No inhibition of azoreduction of 1c or 1d was obtained by addition of 1e, 1g, or 2g to the reaction mixture. In the presence of hepatic microsomes, a type I binding spectrum was obtained for 1d and type II binding spectra for 1a, 1b and 1c, the reactive azo dyes. In contrast, very weak binding was observed for the unreactive compounds 1e, 1f, 1g and 2g. Thus, there is good correlation between binding and substrate reactivity. The apparent lack of binding may explain the inability of the non-reactive compounds to inhibit azoreduction. The difference in the reduction rate observed for 1g vs. 1d suggested that hydroxylation would facilitate the reduction of an otherwise non-reactive azo dye. Support for such a mechanism was obtained in two experiments. In the first, marked facilitation of azoreduction of both the inactive compounds, 2g and 2f, was seen when they were incubated with microsomes under aerobic conditions where preliminary hydroxylation can occur. In the second, azobenzene was initially incubated aerobically with microsomes from phenobarbital- or beta-naphthoflavone-induced rats. The hydroxyazobenzene formed was then readily reduced anaerobically by microsomes from untreated rats. PMID- 2914331 TI - In vitro studies of the inhibition of protein kinase C from rat brain by di-(2 ethylhexyl)phthalate. AB - The environmental contaminant di(2-ethylhexyl)phthalate (DEHP) has been shown to inhibit the phosphorylation of histone by purified protein kinase C (PK-C) from rat brain in a concentration-dependent manner. The inhibition does not involve making the substrate unavailable, although DEHP does bind to some extent to histone. DEHP displaces phorbol dibutyrate from PK-C, indicating that DEHP binds to the regulatory domain of the enzyme. Since DEHP does not affect the PK-C dependent phosphorylation of protamine, DEHP probably does not bind at the catalytic site. DEHP non-competitively blocked activation of PK-C by either phosphatidyl serine or calcium ion. Inhibition of histone phosphorylation by DEHP was enhanced if diglyceride was present, and the enhancement was stereoselective for the isomeric form of the diglyceride. The mechanism of the inhibition is thought to involve interference with the interaction between calcium ion and the regulatory domain of PK-C, and would have significance only for those PK-C substrates that require calcium activation of the enzyme. Thus the presence of DEHP in the high nanomolar concentration range alters the effective substrate specificity of PK-C. PMID- 2914332 TI - Outpatient anaesthetic consultations for pregnant patients. PMID- 2914333 TI - Hyperbaric pressure does not affect the analgesia produced by nitrous oxide in the mouse. AB - Hydrostatic pressure antagonizes some, but not all, of the phenomena associated with general anaesthesia. For example, while unconsciousness produced by general anaesthesia in a wide variety of species is reversed by compression, anaesthetic induced inhibition of synaptic transmission is potentiated by application of pressure. To date, the effect of pressure on analgesia has not been evaluated. In this study, hyperbaric pressure of 75 ata did not antagonize analgesia which had been produced by exposure of mice to 1.2 ata of nitrous oxide. However, the same hyperbaric pressure restored righting in animals which had been anesthetized with 1.5 ata of nitrous oxide. These data add to the suggestion that the multiple effects of general anaesthetics may be mediated at different loci. PMID- 2914334 TI - The influence of collateral vascularisation on haemodynamic performance during abdominal aortic surgery. AB - The extent of periaortic collateral vascularisation has been proposed as a possible mechanism of an altered haemodynamic response to infra-renal aortic cross-clamp in patients undergoing by-pass grafting for aorto-iliac occlusive disease (AOD) compared with patients undergoing abdominal aortic aneurysm (AAA) resection. The haemodynamic responses following clamping, during the clamp time and following clamp release were studied in 18 patients undergoing AAA resection and 12 patients undergoing bypass grafting for AOD. The role of preoperative aortography in predicting cardiovascular performance during aortic vascular surgery was assessed. During the cross-clamp period LVSWI and CI decreased while SVR increased in the AAA group while the AOD group showed an improved CI, stable LVSWI and reduced SVR, which correlated with the extent of periaortic vascularisation on preoperative aortography. Chronic collateral circulation associated with AOD may permit continuous lower extremity perfusion during aortic cross-clamp. The extent of periaortic collateralisation may influence the choice of monitoring techniques and anaesthetic management. PMID- 2914335 TI - Measuring gastric contents during general anaesthesia: evaluation of blind gastric aspiration. AB - Various medications have been reported to decrease gastric content volume and thus risk for pulmonary aspiration. The majority of studies have used blind gastric tube aspiration of stomach contents as the method of measuring the volume of gastric contents. This study evaluated the accuracy of this method by first measuring gastric content volume using blind gastric aspiration and then aspirating residual content in the stomach, using a visually guided flexible fiberoptic gastroscope. Ten obese patients undergoing elective surgery were studied. Gastric contents were collected using a multi-orificed gastric tube and blind aspiration. Immediately after this was completed, residual gastric volume was collected using a visually guided gastroscope. The sum of these two aspirate volumes (true total gastric volume) was statistically compared with the blind aspirate volume. The blind aspirate volume underestimated true total gastric volume by an average of 14.7 ml and was significantly different from true total gastric volume (p less than 0.05). Blind gastric aspiration was thus demonstrated only to approximate true gastric volume. Its use to measure precisely gastric volume cannot, therefore, be recommended. PMID- 2914336 TI - The effect of preoperative apple juice on gastric contents, thirst, and hunger in children. AB - The effect of 3 ml.kg-1 of apple juice given 2.6 +/- 0.4 hours preoperatively was investigated in 80 healthy children of ages five to ten years in this prospective, randomized, single blind study. The children who drank apple juice preoperatively had decreased gastric volume, thirst, and hunger (p less than 0.05). The gastric volume in the control group was 0.43 +/- 0.46 ml.kg-1 and in the patients who received apple juice the gastric volume was 0.24 +/- 0.31 ml.kg 1. The gastric pH was not significantly different, with the control group's gastric pH being 1.7 +/- 0.6 and the treated group's pH was 2.2 +/- 1.2. Further studies of the effects of different volumes and timing of preoperative clear fluids are indicated in paediatric patients. PMID- 2914337 TI - Interscalene brachial plexus blockade with lidocaine in chronic renal failure--a pharmacokinetic study. AB - Plasma lidocaine concentrations, latency of onset, and duration of anaesthesia, were determined after interscalene brachial plexus block in 16 patients presenting for elective upper limb surgery. Eight patients had normal renal function and eight had chronic renal failure, as determined by creatinine clearance. Significantly higher plasma lidocaine levels were recorded ten minutes after infiltration in patients with chronic renal failure (p less than 0.05). Cmax plasma levels for normal patients (5.6 +/- 1.1 micrograms.ml-1) and for patients with chronic renal failure (6.6 +/- 1.6 micrograms.ml-1) were not significantly different. The latency of onset and duration of anaesthesia were similar in both groups. One per cent lidocaine solution may be administered to patients with normal and impaired renal function to provide effective brachial plexus blockade for short surgical procedures. PMID- 2914338 TI - Pneumomediastinum during general anaesthesia: a case report. AB - A case is reported of a pneumomediastinum which presented as an unexplained dysrhythmia during a routine general anaesthestic in a previously fit 19-year-old girl. The possible precipitating factors in this case are discussed along with a description of the signs and symptoms and an outline of its management. PMID- 2914339 TI - Rewarming following hypothermic cardiopulmonary bypass in the malignant hyperthermia-susceptible patient: implications for diagnosis and perioperative management. AB - A 55-year-old, malignant hyperthermia-susceptible patient underwent myocardial revascularization without incident. Six hours postoperatively, he developed what was initially diagnosed as an MH crisis, for which he received intravenous dantrolene. The resultant muscle weakness prolonged the duration of postoperative mechanical ventilation and likely contributed to the development of a postoperative pneumonia. Plasma dantrolene levels were measured for the first 48 hours postoperatively and correlated with clinical findings. On reviewing the patient's perioperative course, it was felt that the hypermetabolic state was not due to MH. The patient's pattern of rewarming following hypothermic cardiopulmonary bypass was similar to non-MH-susceptible patients. Because of the difficulty in diagnosing a MH crisis after hypothermic bypass, it is recommended that patients receive prophylactic dantrolene preoperatively and after bypass. Nondepolarizing muscle relaxants should be given postoperatively to prevent shivering and respiratory acidosis while patients rewarm. PMID- 2914340 TI - Immediate detection of irrigant absorption during transurethral prostatectomy: case report. AB - A transurethral prostatic resection is described in which immediate detection of a rapid massive irrigant absorption could be made by the use of ethanol-tagged irrigating fluid and repeated measurements of the ethanol concentration in the patient's expired breath. This monitoring enabled the surgeon to prevent further absorption by concluding the operation before symptoms resulted. Furosemide was given immediately to promote renal excretion of the absorbed irrigant, and the intravenous infusions were temporarily restricted to limit the intravascular fluid load. In retrospect, volumetric measurement showed that a total of 2410 ml of irrigant had been absorbed. PMID- 2914341 TI - Anaesthesia for a patient with Friedreich's ataxia and cardiomyopathy. AB - Friedreich's ataxia is an inherited neuromuscular disorder often associated with significant cardiac disease. We report a case of Friedreich's ataxia in a 13-year old girl with ulcerative colitis and hypertrophic cardiomyopathy who was successfully managed for subtotal colectomy with general anaesthesia and epidural narcotic. Anaesthetic considerations included the maintenance of fluid volume and stable cardiovascular variables in the intra- and postoperative periods. PMID- 2914342 TI - Postoperative ventilatory and circulatory effects of extended rewarming during cardiopulmonary bypass. AB - Postoperative effects of extended rewarming (ECR) after hypothermic cardiopulmonary bypass (CPB) were studied. All (n = 28) patients were rewarmed to a nasopharyngeal temperature exceeding 38 degrees C before terminating CPB. In 12 patients (control group) the rectal temperature (Tre) was 33.8 +/- 1.7 degrees C (mean +/- sd) at termination of CPB. In sixteen patients (ECR group) rewarming during CPB was continued to a Tre of 36.8 +/- 0.5 degrees C. Postoperative body temperatures, heat content, shivering, oxygen uptake, CO2 production and haemodynamic variables were measured. ECR reduced the heat gain required to complete core rewarming to 665 +/- 260 kJ, compared with 1037 +/- 374 kJ in the control group (p less than 0.01). The incidence of shivering was reduced (p less than 0.05) as well as shivering intensity and duration. In seven non-shivering ECR group patients this coincided with significantly reduced metabolic and ventilatory demands but these improvements were not valid for the group as a whole. The required ventilation temporarily during postoperative rewarming in both groups increased to 250 per cent of the basal need. Extending CPB rewarming (to at least 36 degrees C Tre) was inefficient when used as the sole measure to reduce the untoward effects of residual hypothermia during recovery after cardiac surgery with hypothermic CPB. PMID- 2914343 TI - Development of coronary heart disease in familial hypercholesterolemia. AB - We studied the development of coronary artery disease in 10 homozygous and 692 heterozygous patients with familial hypercholesterolemia. Seventy-five (22%) male heterozygotes and 35 (10%) female heterozygotes were affected by myocardial infarction, which was first noted in men in the 3rd decade of life and in women in the 4th decade of life. Thirty-eight (70%) out of the deceased 54 heterozygous patients died of coronary heart disease. The mean age at death was significantly less in male heterozygotes (54 years) than in female heterozygotes (69 years). Five homozygous and 105 male and 56 female heterozygous patients received coronary angiographic evaluation. The regression equations between age (X) and coronary stenosis index (Y) obtained by assigning score (0 to 5) to each of 15 coronary artery segments were Y = 1.57X - 20.43 (r = 0.956, p less than 0.05) in the homozygotes, Y = 0.52X - 9.11 (r = 0.438, p less than 0.001) in the male heterozygotes, and Y = 0.47X - 12.54 (r = 0.343, p less than 0.01) in the female heterozygotes. From these data, we can assume that coronary artery stenosis detectable by angiography will occur after 17 and 25 years of age in male and female heterozygotes, respectively, and the treatment of heterozygotes with lipid lowering drugs can be delayed until late adolescence. PMID- 2914344 TI - Visualization of subendocardial myocardial ischemia with myocardial contrast echocardiography in humans. AB - Previous studies indicate the degree of myocardial echo contrast enhancement may be related to regional myocardial perfusion. In this study, myocardial contrast echocardiography was used to characterize changes in the transmural myocardial blood flow distribution that were provoked by rapid atrial pacing in 11 patients with one-vessel coronary artery disease. Ten patients without coronary artery disease served as controls. Myocardial contrast echocardiography was performed by intracoronary injection of 2 ml hand-agitated amidotrizoate sodium meglumine (Urografin-76) and by imaging a short-axis view of the left ventricle with two dimensional echocardiography before and during injection of the contrast agent. The two-dimensional echocardiographic images at end diastole, before and after injection of the contrast agent, were digitized off-line into a 512 x 512 pixel matrix with 256 gray levels/pixel to quantify the degree of the enhancement of the peak gray level after injection. Transmural myocardial blood flow distribution was evaluated by measuring the ratio of the enhanced gray level in the endocardial half (endo) to that in the epicardial half (epi) (endo:epi gray level ratio) in the anteroseptal, posterolateral, and inferior segments before and just after rapid atrial pacing in each patient. In patients without coronary artery disease, there were no differences in the endo:epi gray level ratio between any of the three segments both before and after pacing. Mean values of the three segments were 0.95 +/- 0.08 before pacing and 0.90 +/- 0.13 after pacing, respectively. In contrast, in patients with coronary artery disease, the endo:epi gray level ratio for the segment supplied with stenotic coronary artery decreased after pacing (0.40 +/- 0.21 vs. 0.93 +/- 0.18, p less than 0.01), probably reflecting subendocardial myocardial ischemia, whereas that for the segment supplied with nonstenotic coronary artery remained unchanged (0.88 +/- 0.20 vs. 0.99 +/- 0.23, NS). Thus, changes in transmural myocardial blood flow distribution with rapid pacing, which may be due to transient subendocardial ischemia, are visualized with myocardial contrast echocardiography. PMID- 2914345 TI - Sustained bundle branch reentry as a mechanism of clinical tachycardia. AB - The incidence of sustained bundle branch reentrant (BBR) tachycardia as a clinical or induced arrhythmia or both continues to be underreported. At our institution, BBR has been the underlying mechanism of sustained monomorphic ventricular tachycardia in approximately 6% of patients, whereas mechanisms unrelated to BBR were the cause in the rest. Data gathered from 20 consecutive patients showed electrophysiologic characteristics that suggest this possibility. These include induction of sustained monomorphic tachycardia with typical left or right bundle branch block morphology or both and atrioventricular dissociation or ventriculoatrial block. On intracardiac electrograms, all previously published criteria for BBR were fulfilled, and in addition, whenever there was a change in the cycle length of tachycardia, the His to His cycle length variation produced similar changes in ventricular activation during subsequent complexes with no relation to the preceding ventricular activation cycles. Compared with patients with ventricular tachycardia due to mechanisms unrelated to BBR, patients with BBR had frequent combination of nonspecific intraventricular conduction defects and prolonged HV intervals (100% vs. 11%, p less than 0.001). When this combination was associated with a tachycardia showing a left bundle branch block pattern, BBR accounted for the majority compared with mechanisms unrelated to BBR (73% vs. 27%, p less than 0.01). The above finding in patients with dilated cardiomyopathy should raise the suspicion of sustained BBR because dilated cardiomyopathy was observed in 95% of the patients with BBR. Twelve of the 20 patients were treated with antiarrhythmic agents, and the other eight were managed by selective catheter ablation of the right bundle branch with electrical energy. Our data suggest that sustained BBR is not an uncommon mechanism of tachycardia; it can be induced readily in the laboratory and is amendable to catheter ablation by the very nature of its circuit. The clinical and electrophysiologic features outlined in this study should enable one to correctly diagnose this important arrhythmia. PMID- 2914346 TI - The human atrial strength-interval relation. Influence of cycle length and procainamide. AB - We defined the atrial strength-interval relation in 23 patients at cycle lengths of 600, 450, and 300 msec before and after procainamide. The atrial diastolic threshold was similar at cycle lengths of 600 and 450 msec, but the threshold at 300 msec was significantly higher than that determined at 600 and 450 msec both before and after procainamide. Procainamide significantly increased the diastolic threshold only at a cycle length of 300 msec. The strength-interval relation was nonlinear, showing progressively decreasing decrements in the measured refractory period as the stimulating current was increased. Progressive decreases in the drive cycle length from 600 to 450 to 300 msec caused similar decreases in refractory periods. The shape of the curves was similar at cycle lengths of 600 and 450 msex. However, at low current strengths, the slope of the curve determined at 300 msex was significantly more vertical than the slopes of the curves at the longer drive cycle lengths. Procainamide caused similar increases in apparent refractory periods at each paced cycle length. Procainamide did not alter the shape of the curves at any paced cycle length. These observations confirm the importance of stimulation frequency on atrial excitability. They suggest that the effects of procainamide on the effective refractory period of the atrium are not cycle length dependent, although the drug effects on threshold are dependent on the drive cycle length. PMID- 2914347 TI - Evidence of endothelial dysfunction in angiographically normal coronary arteries of patients with coronary artery disease. AB - Acetylcholine causes endothelium-dependent dilation of normal arteries in most animal species. The effect of acetylcholine on normal human coronary arteries is controversial. Pathologic studies and epicardial echocardiography have shown that diffuse atherosclerosis is often present despite angiographic evidence of discrete coronary artery disease (CAD). Therefore, we postulated that acetylcholine would cause vasoconstriction of coronary arteries that are angiographically normal in patients with CAD. Coronary artery diameter, measured by automated quantification of digitized cineangiograms, was determined before and after the intracoronary infusion of 0.2 mM acetylcholine at 0.8-1.6 ml/min. The diameter of stenotic or irregular segments of six atherosclerotic coronary arteries decreased from 1.80 +/- 0.42 mm before acetylcholine to 1.26 +/- 0.46 mm after acetylcholine (p = 0.0025). Acetylcholine had a significantly different effect on the diameter of two groups of coronary arteries that are angiographically normal. Acetylcholine caused a 0.16 +/- 0.09-mm increase in the diameter of 14 normal coronary arteries in patients without CAD, whereas it caused a 0.26 +/- 0.12-mm decrease in the diameter of 14 normal coronary arteries in patients with CAD (p less than 0.01). Thus, the normal response to intracoronary acetylcholine is vasodilation, suggesting that endothelium-derived relaxing factor is released from normal human coronary endothelium. The vasoconstrictive effect of acetylcholine in the angiographically normal coronary arteries of patients with CAD suggests the presence of a diffuse abnormality of endothelial function. PMID- 2914348 TI - A decision scheme for coronary angiography after acute myocardial infarction. AB - It is important to select patients in the convalescent phase of acute myocardial infarction in whom knowledge of coronary anatomy may identify those potentially suitable for intervention aimed at improving prognosis. However, differing guidelines have been proposed, and by applying some of these guidelines to our large database of patients after acute myocardial infarction, several problem areas were identified. These include lack of considering patients with resting ischemia beyond day 5 of hospitalization, management of patients with reduced ventricular function or patients not exercise tested, and the role of coronary angiography in the elderly. Based on this experience and further analysis in 1,848 patients surviving beyond day 5 of hospitalization, a modified decision scheme for coronary angiography was developed and then tested in a second population (n = 780). In the new scheme, patients over 75 years of age are considered individually. Those under 75 years of age with severe resting ischemia in the hospital at any time beyond the first 24 hours (18% mortality between day 6 and year 1), and hospital survivors with a history of previous myocardial infarction and clinical or radiographic signs of left ventricular failure in the hospital (25% 1-year mortality after discharge), are recommended for coronary angiography. Among the remaining patients, some will perform an exercise test, and those with an ischemic response or poor workload (11% 1-year mortality) are also assigned to coronary angiography. When an exercise test is not performed, a resting radionuclide left ventricular ejection fraction is recommended, and coronary angiography is considered if the value lies between 0.20 and 0.44 (12% 1 year mortality). This relatively simple scheme does not make general recommendations in the elderly, considers patients with in-hospital left ventricular failure or reduced left ventricular function or both, and approaches the problem of patients who do not perform an exercise test. This general approach would avoid early coronary angiography in patients with an average 1 year mortality risk after discharge of 3% and recommend coronary angiography in those at increased risk (average mortality rate, 16%) who make up about 55% of this population under 75 years of age. PMID- 2914349 TI - Leisure time physical activity and coronary heart disease death. The US Railroad Study. AB - Seventeen to 20 years of mortality follow-up were used to study the relation of leisure time physical activity (LTPA) to coronary heart disease mortality and to all-cause mortality in white male US railroad workers (n = 3,043). This cohort was initially examined from 1957 to 1960, reexamined from 1962 to 1964, and followed until 1977 or death. LTPA was ascertained by a precursor of the Minnesota Leisure Time Physical Activity Questionnaire. The risk estimate for coronary heart disease death, after adjusting for age, was 1.39 for sedentary men who expended 40 kcal/wk in LTPA compared with very active men who expended 3,632 kcal/wk. This relation was attenuated by adjusting for other coronary heart disease risk factors, but it remained independent and significant. Caloric expenditure in light and moderate activity, as well as that performed in any intense activity, showed independent relations to cardiovascular death and all cause mortality. Associations were slightly stronger in occupationally sedentary men. These results support the hypothesis that physical activity protects against death from coronary heart disease and all-cause mortality. PMID- 2914350 TI - Exercise training in patients with chronic heart failure delays ventilatory anaerobic threshold and improves submaximal exercise performance. AB - We have recently demonstrated that exercise training can induce important hemodynamic and metabolic adaptations in patients with chronic heart failure due to severe left ventricular dysfunction. This study examines the accompanying changes in submaximal exercise performance and the ventilatory response to exercise in these patients. Before and after 16-24 weeks of exercise training, subjects underwent two symptom-limited bicycle exercise tests, one with an incremental graded workload, and one with a constant workload that represented 79 +/- 11% of the pretraining peak oxygen consumption. Breath-by-breath expired gas analysis was performed continuously during each test, and central hemodynamic, leg blood flow, and blood lactate measurements were obtained during the incremental protocol. The ventilatory anaerobic threshold was determined during the incremental exercise study from coplotted breath-by-breath ventilatory data with standard criteria by observers who were unaware of patient identity or training status. As previously reported, exercise training increased peak oxygen consumption by 23% from 16.8 +/- 3.8 to 20.6 +/- 4.7 ml/kg/min and reduced blood lactate levels during submaximal exercise. The training-induced decrease in lactate accumulation was accompanied by a decrease in carbon dioxide production, respiratory exchange ratio, and ventilation during submaximal exercise. The ventilatory anaerobic threshold was delayed from 284 +/- 43 to 352 +/- 91 seconds of exercise (p = 0.02), and it occurred at an increased oxygen consumption (10.1 +/- 1.2 vs. 12.1 +/- 2.6 ml/kg/min, p = 0.01). Exercise duration during the constant workload protocol increased from 938 +/- 410 to 1,429 +/- 691 seconds (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2914351 TI - Mitral prosthesis malfunction. Comparative Doppler echocardiographic studies of mitral prostheses before and after replacement. AB - To assess the influence of mitral prosthesis malfunction on various Doppler echocardiographic indexes, we studied the changes in the peak mitral flow velocity during early diastolic filling phase (Vmax), the mean transprosthesis pressure drop from the simplified Bernoulli equation, the mitral valve area by the pressure half-time method, and the left ventricular isovolumic relaxation time in 15 patients before and after replacement of the malfunctioning mitral prosthesis using continuous wave Doppler echocardiography. Examination of the 15 replaced prostheses revealed a torn or perforated leaflet in 12 valves and a sewing ring dehiscence in one valve. Additional restricted leaflet motion (classified as mild obstruction) was seen in three of these 13 valves. In the remaining two valves, severe prosthesis obstruction was noted. Changes in the Doppler indexes between the preoperative and postoperative study were present in all patients regarding Vmax (mean, 2.2 +/- 0.3 versus 1.6 +/- 0.2 m/sec; p less than 0.001), mean gradient (mean, 9 +/- 5 versus 5 +/- 0.8 mm Hg; p less than 0.001), and isovolumic relaxation time (mean, 47 +/- 12 msec versus 80 +/- 13 msec; p less than 0.001). The mean mitral valve area remained virtually unchanged (2.3 +/- 0.9 versus 2.6 +/- 0.3 cm2; p = NS) but increased postoperatively in each patient with preoperative mild or severe prosthesis obstruction without concomitant aortic regurgitation. Our conclusion is that the peak mitral flow velocity, the mean gradient, and the isovolumic relaxation time are useful parameters in the differentiation of normal and abnormal mitral prosthesis function but may not define the underlying lesion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2914352 TI - Differentiation of constrictive pericarditis and restrictive cardiomyopathy by Doppler echocardiography. AB - Doppler ultrasound recordings of mitral, tricuspid, aortic, and pulmonary flow velocities, and their variation with respiration, were recorded in 12 patients with a restrictive cardiomyopathy and seven patients with constrictive pericarditis. Twenty healthy adults served as controls. The patients with constrictive pericarditis showed marked changes in left ventricular isovolumic relaxation time and in early mitral and tricuspid flow velocities at the onset of inspiration and expiration. These changes disappeared after pericardiectomy and were not seen in patients with restrictive cardiomyopathy or in normal subjects. The deceleration time of early mitral and tricuspid flow velocity was shorter than normal in both groups, indicating an early cessation of ventricular filling, but only patients with restrictive cardiomyopathy showed a further shortening of the tricuspid deceleration time with inspiration. Diastolic mitral and tricuspid regurgitation was also more common in the patients with restrictive cardiomyopathy. These results suggest that patients with constrictive pericarditis and restrictive cardiomyopathy can be differentiated by comparing respiratory changes in transvalvular flow velocities. In addition, although baseline hemodynamics in the two groups were similar, characteristic changes were seen with respiration that suggest differentiation of these disease states may also be possible from hemodynamic data. PMID- 2914353 TI - Activation mapping of reentry around an anatomic barrier in the canine atrium. Observations during entrainment and termination. AB - We determined total right atrial activation sequences during entrainment and termination of flutter induced in dogs with a surgically induced atrial lesion. This type of atrial flutter is due to circus movement of an impulse around the tricuspid valve orifice. We recorded simultaneously from 96 bipolar intracavity electrodes in the right atrium of the isolated, perfused heart. By constructing isochronal maps, we demonstrated the pattern of atrial activation during atrial pacing protocols that either entrained or entrained and then terminated the reentrant rhythm. We show that during pacing the antidromic wavefront from the paced impulse (An) collides with the orthodromic wavefront from the previous paced impulse (On-1). During entrainment, the site of collision of the orthodromic and antidromic wavefronts was constant during pacing at a fixed rate but shifted in the antidromic direction as the pacing rate increased. Furthermore, the last paced beat was entrained only up to the site of collision of the previous paced beat. During one period of entrainment, termination of the reentrant arrhythmia occurred because On-1 blocked in the reentrant pathway due to refractory tissue left by On-2. However, subsequent An did not collide directly with On as was expected, but rather On blocked by an interaction with tissue left refractory by An. Because On was blocked, no reentry occurred when pacing ended. PMID- 2914354 TI - A new mechanism for atrioventricular nodal gap-vagal modulation of conduction. AB - The well-known paradoxic behavior of atrioventricular conduction, the so-called gap phenomenon, that occurs when impulses within a certain range of coupling intervals are blocked while impulses with shorter coupling intervals are conducted is attributed to differences in properties of refractoriness in neighboring regions of the conduction system. In contrast, in the present study a model was developed showing a similar phenomenon, dependent on different electrophysiologic mechanisms and localized within the atrioventricular node in an isolated rabbit heart tissue preparation (n = 11). The hearts were paced at cycle length of 400-500 msec, and atrioventricular nodal conduction times (A2H2) were measured versus atrial extrastimulus (A1A2) coupling intervals by standard extrastimulus techniques. Postganglionic vagal stimulation was applied in the atrioventricular node as short bursts of subthreshold (for myocardium) stimuli with duration of 50-150 msec, amplitude of 20-800 microA, and absolute phase (delay after A1) of 0-500 msec. Vagal bursts with appropriate parameters consistently produced bimodal conduction curves. Initially, gradual shortening of the A1A2 coupling interval was associated with an increasing A2H2, with an accentuated increase (or even atrioventricular block) within an intermediate A1A2 range. However, further shortening of the A1A2 coupling interval produced a decrease in A2H2, which subsequently was followed by a block at the effective refractory period. Microelectrode recordings indicated that this characteristic bimodal pattern of conduction curves, demonstrating a gap, reflected transient vagally induced hyperpolarization in the N region of the node. In those instances where conduction block occurred and gap was manifest, the most marked hyperpolarization coincided with the time of arrival of midcycle premature extrastimuli, whereas the conduction of extrastimuli with either more or less prematurity was under less-marked vagal influence. Thus, this study demonstrates a new electrophysiologic mechanism producing anomalous conduction curves and the gap phenomenon within the atrioventricular node based on vagal-induced nonuniform recovery of diastolic excitability. PMID- 2914355 TI - Preload-induced curvilinearity of left ventricular end-systolic pressure-volume relations. Effects on derived indexes in closed-chest dogs. AB - End-systolic pressure-volume relations (ESPVRs) were analyzed in 10 closed-chest autonomically blocked dogs before and after volume loading that restored end diastolic volume to its value measured in the control conscious state. Dogs had been previously instrumented with a left ventricular pressure micromanometer and ultrasonic crystals for measurements of major, anteroposterior, and septum-free wall diameters. Left ventricular volume was calculated with an ellipsoidal model in the left ventricular cavity. ESPVRs obtained during caval occlusion after volume loading were curvilinear as shown by the division of the relation into two parts. The initial part of the relation had a significantly smaller ESPVR slope (Ees, 12.0 +/- 1.8 mm Hg/ml) and ESPVR volume-axis intercept (Vd, - 3.5 +/- 0.8 ml) than the final part of the relation (19.5 +/- 3.1 mm Hg/ml and 0.0 +/- 0.6 ml, respectively, p less than 0.01). The end-diastolic volume-peak dP/dt relation showed a similar curvilinearity when end-diastolic volumes were larger than 1.5 1.7 times the minimal end-diastolic volume reached during caval occlusion. ESPVRs were not different during aortic constriction and caval occlusion when end diastolic volume was small. In contrast, with large end-diastolic volumes, Ees and Vd were significantly smaller during caval occlusion than during aortic constriction. The final part of ESPVR (with small end-diastolic volume) had the same slope and intercept as that during aortic constriction. We conclude that preload produces a curvilinearity of ESPVR that significantly modifies derived indexes when the range of preload changes is large. PMID- 2914356 TI - Myocardial reperfusion, limitation of infarct size, reduction of left ventricular dysfunction, and improved survival. Should the paradigm be expanded? PMID- 2914358 TI - Early cardiac care centers. PMID- 2914357 TI - Improvements in exercise electrocardiography. PMID- 2914359 TI - Assessing risk associated with carotid endarterectomy. A statement for health professionals by an Ad Hoc Committee on Carotid Surgery Standards of the Stroke Council, American Heart Association. AB - This position statement provides guidelines for assessing risk associated with carotid endarterectomy and defines the point at which risk is too high to perform surgery for specific indications described below. Morbidity and mortality levels are discussed. This statement does not address indications for surgery or merits of specific medical or surgical treatments. Results of current studies that compare relative risk of various treatments for carotid artery disease are not yet available. PMID- 2914360 TI - Cerebral arteriography. A report for health professionals by the Executive Committee of the Stroke Council, American Heart Association. PMID- 2914361 TI - Isoenzymes and isoforms of CK: what is the score? PMID- 2914362 TI - Free 3-methoxy-4-hydroxyphenylglycol determined in plasma by liquid chromatography with coulometric detection. AB - We describe a simple "high-performance" liquid-chromatographic method for determining free 3-methoxy-4-hydroxyphenylglycol (MHPG) in plasma, with coulometric detection and with 4-methoxy-3-hydroxyphenylglycol (iso-MHPG) as the internal standard. MHPG and iso-MHPG are extracted from plasma into ethyl acetate and the extract is washed with a sodium bicarbonate solution, evaporated, reconstituted, and injected into a 25 x 0.4 cm column packed with 3-micron particles of C18 material. We used a mobile phase of acetate buffer (100 mmol/L, pH 5.0) and methanol (92:8 by vol) and an oxidation voltage of 0.5 V. The detection limit of the assay is 0.1 micrograms/L. The interassay CV for a sample with a mean MHPG concentration of 3.84 micrograms/L was 5.2%. The average absolute recovery for the method was 37%. PMID- 2914363 TI - Heterogeneity of serum creatine kinase isoenzyme MM in myocardial infarction: clinical significance and post-synthetic conversion of "abnormal" sub-bands. AB - We investigated the "abnormal" sub-bands of serum creatine kinase (CK; EC 2.7.3.2) isoenzyme MM in acute myocardial infarction (AMI), using isoelectric focusing in polyacrylamide gels, and compared the patterns with those for non-AMI patients and for athletes with increased CK. The "abnormal" sub-bands a (pI 7.55), b (pI 7.35), c (pI 7.25), d (pI 7.05), e (pI 6.85), f (pI 6.72), g (pI 6.50), h (pI 6.40), i (pI 6.28), j (pI 6.20), and k (pI 6.15), in common with "normal" sub-bands 1 (pI 6.91), 2 (pI 6.65), and 3 (pI 6.35), were less uniformly distributed in the AMI and demonstrated a faster rate of anodal conversion than in the non-AMI patients and athletes. "Abnormal" sub-bands a and b were detected only in the AMI patients. Incubation of myocardial CK-MM, predominantly CK-MM 1, with 2-mercaptoethanol, 15 mmol/L, resulted in conversion to the "abnormal" sub bands b and c. Incubation of myocardial CK-MM with normal serum of low total CK yielded CK-MM 3, which on further incubation with 2-mercaptoethanol, 15 mmol/L, resulted in conversion to the "abnormal" sub-bands f and g. Comparable in vitro incubation of serum from AMI patients gave pattern changes consistent with conversion of CK-MM 1 to b, c; CK-MM 2 to d, e; and CK-MM 3 to f, g. PMID- 2914364 TI - Optimized microturbidimetric assay for fibrinogen. AB - In this assay we measure the turbidity produced by precipitation of plasma fibrinogen with a reagent composed of ammonium sulfate, EDTA, and guanidine hydrochloride. The two-step reagent addition, and use of fixed reaction times, eliminates interference from bilirubin, hemoglobin, and chylomicrons. We checked 135 monoclonal proteins for interference, finding the probability of encountering major interference in samples from adults to be very low, P = 0.0002. The method is calibrated with purified fibrinogen and the response is linear over the range 0-10 g/L. Within-run precision (CV) is less than 2% from 1 to 10 g/L. Correlations with the immunoturbidimetric (r = 0.99), chronometric (r = 0.99), and clotting (r = 0.97) methods were extremely high. PMID- 2914365 TI - Alkaline phosphatase activity from human osteosarcoma cell line SaOS-2: an isoenzyme standard for quantifying skeletal alkaline phosphatase activity in serum. AB - Earlier we described a kinetic assay for quantifying skeletal alkaline phosphatase (ALP) isoenzyme activity in serum. The precision of the assay depends on including ALP standards for the skeletal, hepatic, intestinal, and placental isoenzymes. We wondered whether human osteosarcoma cells could provide an efficient alternative to human bone or Pagetic serum as a source of the skeletal ALP standard. ALP activities prepared from five human osteosarcoma cell lines were compared with a bone-derived ALP standard with respect to heat stability and sensitivity to chemical effectors. Two of the cell lines (SaOS-2 and TE-85) contained ALP activities that resembled the bone-derived standard. We selected SaOS-2 cells for additional evaluation (as a potential source of isoenzyme standard), because they contained 40-50 times more ALP activity than did the TE 85 cells. To include the SaOS-2 cell-derived ALP activity in the quantitative isoenzyme assay, we diluted the enzyme in a solution containing heat-inactivated (i.e., ALP-negative) human serum. Surprisingly, this dilution caused a 60-125% increase in maximum enzyme activity. In the quantitative assay of ALP isoenzyme in serum, the SaOS-2 derived ALP was indistinguishable from the serum skeletal ALP standard, with respect to the above criteria and assay variations. Evidently ALP from SaOS-2 cells is suited as a standard for measuring skeletal ALP activity in this assay. PMID- 2914366 TI - Nonenzymatic stopped-flow fluorimetric method for direct determination of uric acid in serum and urine. AB - A simple, direct, sensitive, and selective stopped-flow method for the fluorimetric determination of uric acid in serum and urine samples is described. The variation of fluorescence intensity during the reaction between uric acid and 1,1,3-tricyano-2-amino-1-propene (triap) in the presence of hydrogen peroxide is monitored. For these kinetic measurements peroxide is monitored. For these kinetic measurements we used a versatile stopped-flow module that can be fitted to any fluorimeter. The linear range of the proposed method is 0.08-3.00 mg of uric acid per liter, and the detection limit is 0.03 mg/L. Within- and between assay CVs and selectivity data are reported. Results for serum and urine samples correlated well with those obtained by the uricase method The proposed method is inexpensive and requires no sophisticated detection equipment. PMID- 2914367 TI - Relative importance of estrogen and progesterone receptor assays as prognostic indicators in primary breast cancer: a short-term study. AB - This short-term study of the relative importance of estrogen and progesterone receptors shows that progesterone receptor correlates better than estrogen receptor with tumor recurrence regardless of lymph-node status. Life-table analysis has effectively identified only two groups of patients that may be classified by progesterone receptor status alone. Progesterone-receptor negativity correlated well with tumors of histological Grade III; estrogen receptor positivity correlated with Grade I and II tumors. The earlier recurrence of Grade III breast tumors may explain why progesterone receptor is a better prognostic indicator than estrogen receptor in short-term studies. PMID- 2914368 TI - A simple liquid-chromatographic method for measuring vitamin B6 compounds in plasma. AB - This relatively simple high-performance liquid chromatographic (HPLC) method for measuring all seven known forms of vitamin B6 in plasma from individuals supplemented with pyridoxine hydrochloride shows good analytical recovery (85 98%) and precision. Within-run and between-run CVs for plasmas supplemented with standards were 4% and 7%, respectively. The major forms of B6 found in unsupplemented plasma from normal subjects were pyridoxal phosphate and 4 pyridoxic acid, with pyridoxal just detectable. The HPLC procedure correlated well (r = 0.94) with a modification of an enzymatic method involving apotryptophanase (Anal Biochem 1972;45:567-76) for measuring plasma pyridoxal phosphate, and also (r = 0.94) with a routine method for determining 4-pyridoxic acid in urine (Clin Chem 1964;10:479-89). Elimination of pyridoxine from the plasma of both normal and hyperoxaluric individuals was shown to be very rapid, with half-lives (t1/2) of 45 and 40 min, respectively. Finally, we present evidence for the existence of two other forms of B6 and discuss the possibility of a new metabolic pathway in vitamin B6 metabolism. PMID- 2914369 TI - Measurement of autoimmune response against collagen types I, III, and IV by enzyme-linked immunosorbent assay, and its application in infective endocarditis. AB - In these enzyme-linked immunosorbent assays for determination of autoantibodies (IgG, IgM) against collagen type I (ACA I), III (ACA III), and IV (ACA IV), we use commercially available antigen preparations. Inhibition curves showed limited cross-reactivity between these different collagen preparations, the major interference being observed after addition of collagen type III in the ACA I procedures. Imprecision (CVs) for high- and low-titer samples ranged between 1.5% and 7.9% (within-run) and 5.5% and 12.7% (between-run) for ACA I, between 2.2 8.7% and 4.5-10.7% for ACA III, and between 1.3-5.9% and 7.4-11.6% for ACA IV. Significantly increased humoral immune response against collagen types I and III (P less than 0.001) could be demonstrated during the first month of infective endocarditis. In contrast, only borderline increases, however constant, of autoimmune response against basement-membrane collagen (ACA IV) were noticed during 90 days of follow-up. PMID- 2914370 TI - Strong association of a single nucleotide substitution in the 3'-untranslated region of the apolipoprotein-CIII gene with common hypertriglyceridemia in Arabs. AB - A potential genetic marker for hypertriglyceridemia and coronary disease, an apolipoprotein-CIII gene allele displaying a single nucleotide substitution, was found in 71% of Arabs with primary hypertriglyceridemia. Over 96% of the unrelated adults possessing this allele showed hypertriglyceridemia. The same allele was found rarely among normotriglyceridemic subjects. In further support of involvement in hypertriglyceridemia, this allele was co-inherited with increased serum triglycerides in a three-generation family. Moreover, a gene dosage effect was also found. A mechanism of action for the allele is suggested by the findings that the subjects possessing the allele show markedly increased very-low-density lipoproteins, decreased high-density lipoproteins, and borderline chylomicronemia demonstrable by lipoprotein electrophoresis. Electrophoresis of the selectively amplified-restricted apolipoprotein-CIII DNA on agarose gel provides a rapid diagnostic test that allows identification of the subjects with this allele in less than a day. PMID- 2914371 TI - A dual-precipitation method evaluated for measurement of cholesterol in high density lipoprotein subfractions HDL2 and HDL3 in human plasma. AB - The dual-precipitation method for measurement of cholesterol in high-density lipoprotein subfractions HDL2 and HDL3 (Warnick et al., Clin Chem 1982;28:1574) was compared with quantification of cholesterol in HDL2 and HDL3 by zonal ultracentrifugation (Patsch et al., J Lipid Res 1974;15:356-66). For 39 plasma specimens differing widely in their HDL subfraction cholesterol concentration, the coefficient of correlation between the two methods was 0.94 for HDL2 cholesterol, 0.82 for HDL3-cholesterol. Storage of plasma specimens at -70 degrees C decreased the apparent content of HDL3-cholesterol by 5%; no significant changes in HDL2-cholesterol were observed. In frozen plasma, interference by apoB-containing lipoproteins and by lipoprotein(a) was negligible. Mean weight ratios of apoA-I to cholesterol were twice as high for HDL3 as for HDL2, reflecting the increased cholesterol content of HDL2. The study suggests that quantification of HDL2 and HDL3 cholesterol by precipitation is appropriate for use in epidemiological studies. PMID- 2914372 TI - A longitudinal study of thyroid function in pregnancy. AB - We undertook a prospective longitudinal study of thyroid function in 36 pregnant women. There were significant increases in thyroxin-binding globulin, thyrotropin, and triiodothyronine. Albumin, free thyroxin (measured by an analog and a nonanalog method), and the free thyroxin index were significantly decreased. Results for the free thyroxin methods were correlated with each other in each trimester. We could find no evidence for artifacts related to albumin or thyroxin-binding globulin with either method for free thyroxin. PMID- 2914373 TI - Greater than expected alanine aminotransferase activities in plasma and in hearts of patients with acute myocardial infarction. AB - Early increases in the activity of alanine aminotransferase (ALT, EC 2.6.1.2) in plasma are observed in about 7% of patients with acute myocardial infarction (AMI), of whom about half die. Some type of liver injury, secondary to AMI, could be responsible for this phenomenon. However, quantitative analysis shows that the release of ALT in most of these patients conforms to the myocardial release pattern. Moreover, extra release of hepatic aspartate aminotransferase (EC 2.6.1.1) is not observed. These findings suggest that the heart may occasionally contain a high ALT activity. This hypothesis was verified by determination of enzyme activities in 10 hearts obtained from patients who died after AMI. The mean ALT activity in these hearts, 21 (SD 12) U per gram wet weight, significantly (P less than 0.01) exceeds the value of 7.7 (SD 4.9) U/g found for seven control hearts and may reflect increased amino acid metabolism in the energy-depleted heart muscle, as described earlier for skeletal muscle. PMID- 2914374 TI - Choosing quality-control systems to detect maximum clinically allowable analytical errors. AB - Critical systematic and random analytical errors for 17 common clinical chemical components were estimated from published values for analytical imprecision, biological variation, and "medically important changes." Appropriate quality control systems for these analytes are discussed on the basis of power considerations. The simple rule 1(3)s, with one control per run, is minimally sufficient for the analytes (about one quarter of those considered here) for which the magnitude of critical error is at least 3 analytical standard deviations. The more powerful rule 1(2)s, with one control per run, is the minimal requirement for analytes for which critical errors are about 2 analytical standard deviations; these are about half the remaining analytes. Greater power values are achieved by using multiple rules based on several controls per run. In general, this study does not support the view put forward by some authors that the quality-control rules in use today are too restrictive. PMID- 2914375 TI - How sensitive are immunometric assays for thyrotropin? AB - The usual method for calculation of the "sensitivity" of thyrotropin immunometric assays is multireplicate analysis of the zero analyte standard. Although this is a statistically valid estimate of the scatter likely to be found in the response variable, it is unrelated to normal analytical practice (usually analysis in duplicate) and estimates intra-assay errors only. This study was designed to assess the analytical performance of 10 immunometric assays used routinely for measurement of thyrotropin in human serum. Response data from each assay were accumulated to provide (a) an estimate of "sensitivity" from multireplicate analysis and (b) an estimate of "minimum detection limit," relating directly to errors associated with routine performance and derived from a minimum of 500 duplicate analyses. We conclude that the "minimum detection limit" should be promoted as a more meaningful measure of assay performance at low analyte concentrations than the "sensitivity" derived from multireplicate analysis of the zero-analyte standard. PMID- 2914376 TI - Determination of physostigmine in plasma and cerebrospinal fluid by liquid chromatography with electrochemical detection. AB - Physostigmine (Phy) was determined in plasma and cerebrospinal fluid (CSF) by HPLC with electrochemical detection, with use of a normal-phase column and methanolic sodium acetate buffer, pH 4.6. The detection limit of the method was 0.5 micrograms/L for a 2-mL sample of plasma or 0.5 mL of CSF. Analytical recovery of Phy in the range from 0.5 to 40 micrograms/L was 60% (SD 5%) for plasma and 78% (SD 8%) for CSF. Excellent chromatographic separation of Phy without column deterioration during extended usage and constant recovery for a wide range of Phy concentrations makes the routine monitoring of plasma from patients with Alzheimer's disease economically feasible. Using our method, we measured Phy in 13 such patients' plasmas at 105 and 135 min after a 135-min intravenous infusion of 300, 600, and 900 micrograms of Phy per square meter of body surface. Mean values significantly increased with dose (P = 0.001), but differences between 105 and 135 min (P = 0.229) or between dose and time (P = 0.949) were not significant. PMID- 2914377 TI - Detection of poisoning by plant-origin cardiac glycoside with the Abbott TDx analyzer. AB - Cardiac glycoside poisoning caused by ingestion of plant material is common in tropical and sub-tropical areas. In evaluating the use of the Abbott TDx Digoxin II assay to detect such cases of poisoning, we found it a rapid and convenient method for confirming the ingestion of glycosides from the plants Nerium oleander, Thevetia peruviana, and Adonis microcarpa, and from the toad Bufo marinus. Here we report some clinical cases illustrating our experience with the use of this assay, and describe results of cross-reactivity studies with compounds structurally similar to digoxin. Because of the competitive nature of the immunoassay as well as the complexity of the mixture of cross-reacting cardiac glycosides present in the plant material, the measured apparent digoxin concentration is not linearly related to the cardiac glycoside concentration. PMID- 2914378 TI - Simultaneous determination of pentoxifylline and three metabolites in biological fluids by liquid chromatography. AB - We describe a sensitive and specific liquid-chromatographic assay for pentoxifylline and three of its metabolites in human plasma and urine. Addition of hydrochloric acid to the sample before extraction, and incorporation of acetic acid in the chromatographic eluent, allow the simultaneous determination of the four compounds plus an internal standard in one chromatographic run. Unlike gas chromatographic procedures, this method does not involve derivatization no similar analysis of serum or plasma samples has been described before now. The method has been applied successfully to routine analysis and to pharmacokinetic studies. PMID- 2914379 TI - Patterns of lactate dehydrogenase isoenzymes 1 and 2 in serum of patients performing an exercise test. AB - Values for total lactate dehydrogenase (LD, EC 1.1.1.27) activity and LD isoenzymes were determined in serum from 56 patients and 40 healthy subjects before and 24, 48, and 72 h after they performed an exercise test. The mean (for all four times) total LD activity concentration and proportion of LD-2 were within the normal range for all 96 subjects. Mean LD-1 values for serum, although within the normal range in all subjects, were significantly higher in patients with positive exercise test results than in subjects with negative results: 75 (SD 12) U/L in 35 patients with ST depression greater than 2 mm; 63 (SD 14) U/L in 16 patients with ST depression of 1-2 mm; 43 (SD 11) U/L in subjects with negative test results, by 48 h after the test. The LD 1:2 ratio was also markedly higher in the group of patients with positive test exercise results, especially in those with ST depression greater than 2 mm (1.02, SD 0.06), compared with those subjects with negative results (0.60, SD 0.04). A similar trend was also found 24 and 72 h after the exercise test. We conclude that exercise-myocardial ischemia may lead to an increased LD 1:2 ratio in serum, and demonstrate a correlation between the degree of ischemia and the LD 1:2 ratio. Determination of the LD 1:2 ratio, even in the presence of normal total LD activity, may assist in the clinical evaluation of patients performing an exercise test. PMID- 2914380 TI - Automated enhanced latex agglutination assay for rheumatoid factors in serum. AB - This improved assay of rheumatoid factors in serum, described here for use with the Baker "Encore" centrifugal analyzer, is efficient, with 250-sample throughput per hour; reproducible, with between-batch CV = 5% and within-batch CV = 2% (mid assay range); and results correlate well (r = 0.9) with those by other methods. The method is fully quantitative and automated, involves no predilution steps, and can be adapted for use in a wide range of systems. It has a sensitivity of 96% and specificity of 80% in diagnosing rheumatoid arthritis. PMID- 2914381 TI - Screening for microalbuminuria in patients with diabetes mellitus: frozen storage of urine samples decreases their albumin content. AB - The influence of storage on urinary albumin concentration was prospectively studied with use of overnight urine specimens (Albustix negative) from 73 diabetic patients. From each urine sample four aliquots were taken. One was stored at 4 degrees C and assayed within two weeks, the other three were stored at -20 degrees C and assayed within two weeks and after two and six months. Albumin concentration was measured with laser immunonephelometry. The detection limit, 1 mg/L, suffices for the screening of diabetic patients for microalbuminuria. After storage for two and six months at -20 degrees C, significantly lower albumin concentrations were found. The difference was mainly caused by lower concentrations found in urine samples in which a precipitate had formed, which was the case in 22 and 25 samples, respectively. Thus, freezing of urine samples for determination of low concentrations of albumin may yield falsely low results. Urine samples are best stored at 4 degrees C and assayed within two weeks. PMID- 2914382 TI - Concentrations of carotenoids, retinol, and tocopherol in plasma, in response to ingestion of a meal. AB - Field studies and epidemiological surveys may necessitate obtaining a blood sample from a nonfasted subject for nutritional assessments. We measured the effect of a standardized test meal, eaten after an overnight fast, on the concentrations of seven carotenoid fractions, retinol, and tocopherol in plasma of eight healthy adults. The 790-calorie test meal did not alter the measured concentrations. We conclude that blood sampled up to 4 h after breakfast can be validly used for these measurements. PMID- 2914383 TI - Assessment of renal function by inulin clearance: comparison with creatinine clearance as determined by enzymatic methods. AB - We compared creatinine clearances determined by enzymatic (Kodak Ektachem 700 single-slide, Boehringer Mannheim creatinine PAP) and nonenzymatic (Jaffe, HPLC) methods with glomerular filtration rate measured by inulin clearance in patients with varying degrees of renal function. The Kodak enzymatic assay gave values for creatinine 2 to 3 mg/L higher than the other methods. This resulted in significantly lower creatinine clearances than inulin clearances and creatinine clearances determined by the other methods. However, correlations between all methods for serum and urinary creatinine values and clearances were good. To avoid between assay (enzymatic vs nonenzymatic) discrepancies, manufacturers should agree to an acceptable standard of calibration under the usual conditions used with patients. PMID- 2914384 TI - Effectiveness of sodium fluoride as a preservative of glucose in blood. AB - How effective is sodium fluoride as a preservative of blood glucose? We compared changes in glucose concentration in fluoride-treated blood specimens with those of heparin-treated specimens. The former declined rapidly during the first hour; thereafter the rate of decrease was slower, and after 4 h the glucose concentration in the blood samples remained stable for up to three days. In contrast, the glucose concentration in the heparin-containing samples declined continuously. During the first hour, however, the rates of decline in the two types of samples were similar. Evidently sodium fluoride takes effect slowly but effectively in preserving glucose in blood for at least three days. Its use, however, is unnecessary if the concentration of glucose is to be measured within the first hour after sampling. PMID- 2914385 TI - Homogentisic acid determined in biological fluids by HPLC. AB - In this rapid, specific, and sensitive high-performance liquid-chromatographic method of analysis for homogentisic acid in biological fluids, homogentisic acid is separated on a column of Nucleosil CN. This method, which we applied to the diagnosis of three cases of alcaptonuria, represents a suitable analytical tool for the diagnosis of alcaptonuria. PMID- 2914386 TI - Indole compounds do not cause false positives with the TDx cannabinoid assay. PMID- 2914387 TI - Comparison of free digoxin and total digoxin: extent of interference from digoxin like immunoreactive substances (DLIS) in a fluorescence polarization assay. PMID- 2914388 TI - Evaluation of the Ames Seralyzer for therapeutic drug monitoring of phenobarbital and phenytoin. PMID- 2914389 TI - An enzymatic method for lactate in whole blood adapted to the Cobas Bio. PMID- 2914390 TI - Pyruvate measured in whole blood with the Cobas Bio analyzer. PMID- 2914391 TI - Chemiluminescent determination of nonesterified fatty acids in serum. PMID- 2914392 TI - Enzymatic assay of salicylate adapted to the Monarch centrifugal analyzer. PMID- 2914393 TI - Commercially available dissociation-enhanced lanthanide fluoroimmunoassay kit evaluated for quantifying ferritin in serum. PMID- 2914394 TI - Relationship between plasma cholesterol and total and ionized calcium concentrations in serum from postmenopausal women. PMID- 2914395 TI - Measurement of alkaline phosphatase activity by kodak Ektachem 700 XR analyzer compared with other routine analytical methods. PMID- 2914396 TI - Sampling distribution of skewness and kurtosis. PMID- 2914397 TI - Sample treatment for long-distance transport of plasma for hormone assay. PMID- 2914398 TI - Interactions of copper with some analytes in human serum. PMID- 2914400 TI - Nonprotein components of urine interfere with colorimetry of urinary albumin with bromphenol blue. PMID- 2914399 TI - Plasma malondialdehyde, lipid peroxides, and the thiobarbituric acid reaction. PMID- 2914401 TI - More on oligoclonal bands and diagnosis of multiple sclerosis. PMID- 2914402 TI - Follow-up of monoclonal gammopathies in asymptomatic HIV-infected subjects. PMID- 2914403 TI - Assay of "intact" parathyrin in the immediate and long-term postoperative follow up of patients treated for hyperparathyroidism or thyroid tumor. PMID- 2914404 TI - Deposition of immune complexes containing cationized antibodies in myocardial small blood vessels of mice. AB - Small myocardial blood vessels constitute a site for preferential deposition of preformed cationic immune complexes. This preferential deposition was demonstrated with a limited dose (100 micrograms) of cationized rabbit antibodies to human serum albumin, injected into C57B1/6J mice either alone or in the form of preformed immune complexes. Heart, kidney, liver, intestine, and skeletal muscle were examined for immune deposits by immunofluorescence microscopy. Highly cationized antibodies injected alone showed deposition in glomeruli and in the liver along the sinusoids but not in other tissues. Immune complexes containing native rabbit antibodies deposited only in liver in a Kupffer cell pattern. Moderate and highly cationized antibodies in immune complexes deposited in myocardial small blood vessels, liver, and glomeruli, but not in intestine or skeletal muscle. These complexes deposited via electrostatic interactions since unrelated polycationic molecules, protamine sulfate or cationized rabbit serum albumin, injected 1 min prior to cationic antibodies in immune complexes blocked deposition in myocardial small vessels, glomeruli, and liver. Administration of protamine or cationized rabbit serum albumin 1 min after deposition of cationized immune complexes resulted in displacement of the immune deposits in heart, kidney, and liver, but not when the injection was given 1 hr later. The presented data indicate that with passage of time the immune deposits rearrange and forces other than charge-charge interactions retain them in myocardial vessels. PMID- 2914405 TI - Improved sexual function in hemodialysis patients on recombinant erythropoietin: a possible role for prolactin. AB - As it was reported that correction of anemia in long-term hemodialysis patients by recombinant human erythropoietin (r-HuEPO) is associated with improved sexual function, we conducted the present study to further delineate the mechanism(s) by which this is brought about. Serum prolactin, testosterone, and parathyroid hormone (PTH) levels were followed during 4 months of r-HuEPO therapy. Within 4 months of treatment with r-HuEPO, hematocrit values rose from 23.7 +/- 1.2 to 35.7 +/- 0.2% and hemoglobin increased from 7.3 +/- 0.3 to 11.3 +/- 0.4 g/100 ml. In parallel, serum prolactin values decreased significantly from 66.9 +/- 9.3 to 9.6 +/- 2.6 ng/ml in females and from 39.5 +/- 10.5 to 10.3 +/- 1.0 ng/ml in male dialysis patients. Testosterone concentrations were low in male patients and remained unchanged during r-HuEPO therapy. Baseline PTH values were elevated (1,880 +/- 220 pg/ml) in patients of both sexes and declined to 1,410 +/- 180 pg/ml during treatment with r-HuEPO. However, this difference did not reach statistical significance. Sexual function improved in 4 out of 7 males and 5 out of 9 female patients began to menstruate regularly again. It appears that treatment of anemia in end-stage renal disease by r-HuEPO improves sexual function via normalization of elevated serum prolactin concentrations. PMID- 2914406 TI - Evidence for an HIV-related nephropathy: a clinico-pathological study. AB - The existence of an HIV-related nephropathy as a distinct disease entity is controversial. We observed a high incidence of renal disease in our AIDS patients. Of 182 patients, 59 patients (32.4%) were found to have heavy proteinuria (greater than 2 g/24 h). Of these, 24 patients had slow progression of renal insufficiency and 2 patients had rapid deterioration to end stage renal disease. There was a notable absence of hypertension in these cases. The incidence of proteinuria was similar in blacks and hispanics; however 22.8% of blacks had renal insufficiency as compared to 6.9% of hispanics. There was no difference in the incidence of heavy proteinuria between intravenous drug abusers (32.3%) and nonabusers (33.3%). Renal morphology when examined showed characteristic changes, including cytomembranous structures and virus-like particles. These changes were similar in patients with heavy or light proteinuria, though they were less severe in the latter. We conclude that a HIV related nephropathy exist and the presence of cytomembranous structures and virus like particles in the renal tissue raises the possibility of a viral etiology for this disorder. PMID- 2914407 TI - Contrasting response to cyclosporin in refractory nephrotic syndrome. AB - We studied the effects of cyclosporin A (CsA), given for three months, in 14 patients with nephrotic syndrome refractory to treatment with prednisone and/or other immunosuppressants. CsA was given in a starting dose of 6 mg/kg and plasma through levels (RIA) were kept between 50 and 150 ng/ml. Diagnosis included: idiopathic membranous glomerulonephritis (n = 6), focal segmental glomerulosclerosis (n = 3), minimal change disease (n = 3) and membranoproliferative glomerulonephritis (n = 2). Three patients with non immunologically mediated nephrotic syndrome due to Alport's syndrome were studied as well. Considering all patients and diagnostic groups together, proteinuria decreased from 9.0 +/- 4.3 to 4.7 +/- 3.8 g/24 h during CsA treatment (mean +/- SD; p less than 0.01). However, serum creatinine increased from 121.8 +/- 60.5 to 150.4 +/- 64.6 mol/l (p less than 0.01) and glomerular filtration rate as estimated by 24-hour creatinine clearance fell from 85.5 +/- 33.7 to 72.1 +/- 37.2 ml/min (p less than 0.05). When compared to other diagnostic groups, fractional excretion of protein, i.e. protein excretion corrected for changes in glomerular filtration rate, fell only in IMGN (ANOVA, p less than 0.05). We conclude that CsA reduced proteinuria in patients with refractory nephrotic syndrome. In the majority of these patients this reduction could be due to a renal hemodynamic, rather than an immunomodulatory effect of the drug. Only in IMGN the latter action of the drug may be of importance. PMID- 2914408 TI - The effect of vitamin C supplementation and withdrawal on the mortality and morbidity of regular hemodialysis patients. AB - The present study was undertaken to evaluate the effects of vitamin C supplementation (VC-S) on the morbidity and mortality of 61 clinically stable outpatients maintained on regular hemodialysis (HD). All patients were given vitamin C (500 mg daily) for 2 years and observed for a further 2 years on no treatment. VC-S significantly increased the plasma levels of ascorbic acid up to 7.8 mg/dl (mean 3.3 +/- 0.4 s.e.m.) which fell after withdrawal to the normal range (mean 1.2 +/- 0.2 mg/dl). Hyperoxalemia was aggravated by VC-S (mean 61.5 +/- 3.3 mumol/l, range 33.3 to 165.5) while plasma oxalate levels in the unsupplemented period decreased to 36.3 +/- 3.3 mumol/l (p less than 0.01). There were no differences in creatinine, hematocrit, blood transfusion requirement, morbidity (including hospitalization) or mortality between the two periods of time in the same patients. In conclusion, we could not find any beneficial effects on morbidity or mortality as a result of using VC-S in regular HD patients. However, secondary hyperoxalemia was aggravated. As a result of these observations it appears that VC-S is harmful and unnecessary in these patients provided they are on an adequate diet. PMID- 2914409 TI - Hyperaluminemia in renal failure: the influence of age and citrate intake. AB - Following the occurrence of aluminum encephalopathy in four patients with chronic renal failure, we studied 34 azotemic patients seen during the same year and five volunteers who took varying combinations of aluminum hydroxide and an alkalinizing citrate (Shohl's) solution. We found that the four encephalopathic cases were older than the 34 azotemic patients (68 years +/- 14 SD, vs 50 +/- 13, p less than 0.05), had a higher mean serum aluminum value (727 micrograms/l +/- 320 vs 92 +/- 73, p less than 0.005), had taken more aluminum hydroxide (5 g/day +/- 0.9 vs 1.6 +/- 1.8, p less than 0.01), and more Shohl's solution (64 ml/day +/- 19 vs 20 +/- 29, p less than 0.01). In all 38 patients the serum aluminum values correlated directly with age (p = 0.01), aluminum hydroxide (p = 0.001) and concomitant citrate intake (p = 0.004). In the five healthy volunteers the 24 hour urinary aluminum excretion increased from a baseline of 22 micrograms +/- 19 SD to 167 +/- 109 (p = 0.05) during aluminum hydroxide intake, rising to 580 +/- 267 (p = 0.01) during the simultaneous intake of citrate and aluminum hydroxide. Corresponding serum aluminum values were 11 micrograms/l +/- 2 SD, 44 +/- 34 (p = 0.1), and 98 +/- 58 (p less than 0.05). Thus citrate seems to enhance aluminum absorption and may cause encephalopathy in patients with chronic renal failure, especially the elderly. PMID- 2914410 TI - Berger's disease: Henoch-Schonlein syndrome/one disease entity. PMID- 2914411 TI - Fatal acute renal failure after piroxicam. PMID- 2914412 TI - Hemodynamics of patients with renal failure treated with recombinant human erythropoietin. AB - Hemodynamics were evaluated in 8 patients with uncomplicated renal failure on regular dialysis before and after partial correction of anemia by treatment with recombinant human erythropoietin (r-huEPO). Under r-huEPO treatment, mean (+/- SD) hemoglobin increased from 7.51 (0.60) to 10.27 (0.92) g/dl. Mean blood pressure, body weight, total blood volume and extracellular fluid compartment remained unchanged. Cardiac output as measured with a radionuclide method increased significantly from 4622 (1069) to 5393 (1285) units (p less than 0.02) and peripheral resistance decreased from 22 (4) to 19 (3) units (p less than 0.02). 6-keto-1-alpha-prostaglandin decreased from 96.9 (54.4) to 61.6 (18.0) pg/ml (p less than 0.05) but plasma renin activity, noradrenalin and atrial natriuretic peptide remained unchanged comparing pre- and post-treatment levels. This observation suggests that an increase of red blood cell mass can improve heart function in patients undergoing regular dialysis treatment. PMID- 2914413 TI - Insurability of pediatric gastrointestinal disorders. AB - To assess the insurability of children with gastrointestinal disorders, the authors surveyed by questionnaire 106 health-insurance companies concerning their handling of an application for health insurance for a child with a diagnosed gastrointestinal disorder. They received 24 responses (23%) of which only ten companies (42% of the respondents, 9% of the companies surveyed) completed the questionnaire. Insurance companies generally were not receptive to their inquires. The consensus of the responses was that ultimate insurability is dependent upon review of the medical record. For individual gastrointestinal diseases, responses were variable and often not easily categorized. Many companies encourage applicants previously denied coverage to reapply at a later date. Most pediatric gastrointestinal disorders are not insurable or insurable only at increased rates. Since insurability is dependent upon review of the medical record, the medical record must reflect the diagnosis and prognosis accurately. Education of the insurance industry regarding pediatric gastrointestinal disorders is encouraged. PMID- 2914414 TI - Iron-fortified formulas. Pediatricians' prescribing practices. AB - Primary care pediatricians in Washington State were surveyed regarding their attitudes about iron-fortified formula. Of the 210 responding physicians who stated an opinion 70 (33%) feel that there are definite indications for non fortified formula, and 33 (16%) routinely recommend formula without added iron. Despite evidence that adding iron to formula has helped reduce the prevalence of anemia in children and does not cause gastrointestinal symptoms, iron-fortified formula is not universally recommended by pediatricians. PMID- 2914415 TI - Ulcerative esophagitis. A rare source of upper gastrointestinal bleeding in a neonate. Use of fiberoptic endoscopy for diagnosis. AB - A case of upper gastrointestinal hemorrhage in a newborn infant due to ulcerative esophagitis is described. This is a previously undescribed cause of upper gastrointestinal neonatal bleeding. This case further illustrates the safety and efficacy of fiberoptic endoscopy in elucidating the source of upper gastrointestinal bleeding in the immediate newborn period. PMID- 2914416 TI - Breast feeding preference of Hispanic and Anglo women. 1978-1985. AB - Hispanic women of Mexican origin are one of the fastest growing minority groups in the United States, but little information is available regarding the rate of breast feeding among this group of women. The breast feeding preferences of Hispanic women delivering at a southern California university hospital were determined by retrospective analysis of birth log records from 1978 to 1985. Approximately 95 percent of the Hispanic women delivering at this institution were of Mexican origin. Hispanic women had a preference for breast feeding similar to the national average for the same time period. The rate of breast feeding among Hispanic women of Mexican descent was consistently higher than previous reports from other regions of the United States. PMID- 2914417 TI - Purpura fulminans. A case for heparin therapy. AB - A 6.5-year-old boy developed purpura fulminans. He had no evidence of congenital protein C deficiency. He responded readily to heparin therapy with resolution of his coagulopathy. The coagulopathy resumed rapidly after heparin therapy was interrupted to allow for surgical procedures. Despite correction of his coagulopathy with heparin, surgical amputation of his leg was necessary because of inadequate perfusion. PMID- 2914419 TI - American Society for Clinical Pharmacology and Therapeutics. Abstracts of papers. Ninetieth annual meeting. March 8-10, 1989, Nashville, Tennessee. PMID- 2914418 TI - Typhoid fever. Unusual hepatic manifestations. AB - Four cases of typhoid fever with unusual hepatic manifestations are described. Two cases had hepatitis and two had hepatic abscess. These complications are documented for the first time in the pediatric age group. Awareness of these rare manifestations may be helpful in avoiding unnecessary morbidity and mortality. PMID- 2914420 TI - Rerandomization tests for analyzing correlated data from dental studies. AB - Dental research studies often produce relatively small data sets in which observations are serially or spatially correlated. Rerandomization tests are presented as alternatives to analysis of variance and multivariate analysis for assessing group differences using such data. Rerandomization tests are particularly useful when the investigator is unwilling to make strong assumptions about the nature of the serial correlation or the distribution of the data. Two examples are discussed that demonstrate these techniques. PMID- 2914421 TI - Calculation of survival curves and statistical comparison of two censored populations: a computer program in BASIC. AB - In experimental aging research the handling of censored data imposes a serious problem in the calculation of survival curves of partly censored populations and the statistical comparison of such populations. The presented computer program combines a method to calculate a corrected survival curve and a test to compare two censored populations. In both methods, the proportion of the animals that survive or die during an interval and the number at risk at the start of that interval is used in the calculation of relative survival or death during that interval. The program is written in an elementary BASIC and will run on practically every computer programmable in BASIC. The presented method can be used for testing the difference between survival characteristics of two animal populations but might also be employed in evaluating the effect of a medical treatment. PMID- 2914422 TI - Frequency content of the QRS notching in high-fidelity canine ECG. AB - High-fidelity ECGs, defined as ECG signals including high-frequency components, have been studied and variations in the incidence of fine notches and slurs on the QRS complex were reported in different myocardial pathologies. These observations might be of clinical importance since they suggested a noninvasive marker for cardiac dysfunctions. We studied high-fidelity ECG waveforms displaying pronounced notches and slurs. Signals were obtained from 12 anesthetized dogs. Computer analysis included digital averaging, followed by digital filtering in different frequency bands in order to determine the frequency range corresponding to notches and slurs. Low-pass filtering of the low noise average waveforms was performed while gradually lowering the upper frequency limit, until the fine notch (or slur) could no longer be visually detected, thus determining the lower limit of its frequency content. A band cutoff filter was then applied to the original average waveform. The lower limit of the band cutoff filter was set at the frequency previously determined as the lower limit of the notch (or slur), and its upper limit was determined by gradual raising until the notch (or slur) was visually indistinct. Following this approach, the notches were found to contribute to a frequency range of 40-185 Hz, whereas the slurs contributed only to the lower subrange of this frequency band below 100 Hz. PMID- 2914423 TI - Three-dimensional reconstruction of human limbs from tomographic views. AB - The recently developed medical imaging technique of tomography can be used with amazing success to learn about the interior of a human body. Each tomograph, however, is limited to only one section of the specific human limb. A series of tomographs taken at irregular intervals and various angles would provide three dimensional information of the interior of the limb. Currently available 3-D surface display algorithms have limitations, particularly when applied to clinically important image data requiring fast and flexible interactive analysis. In addition to the problem of computation time is the cost of specialized hardware. A new algorithm has been designed for use with three-dimensional medical images which attempts to overcome these limitations. A computer graphics system is described which reconstructs three-dimensional images from tomographic sectional data. This 3-D surface algorithm can be exploited in planning reconstructive bone surgery. An example which illustrates the versatility and speed of the new algorithm is presented. PMID- 2914424 TI - BUMP: a FORTRAN program for identifying dose-response curves subject to downturns. AB - BUMP is a FORTRAN implementation of a modified Jonckheere-Terpstra test, proposed by Simpson and Margolin, to test nonparametrically for a dose-response curve when a downturn is possible at high doses. The Jonckheere-Terpstra statistic is commonly used to test for increasing or decreasing trends in dose-response relationships. In many experimental settings, however, a test agent has more than one effect, and a "bump"-shaped dose-response can occur. For instance, increasing the concentration of a certain nutrient on a petri dish may increase the growth rate at low doses yet decrease the growth rate at high doses because of toxicity. The modified test allows one to assess the significance of the initial increase in the dose-response curve and yet to minimize the effect on the conclusions of any downturn at higher doses. A complete system which operates directly on SYSTAT/MYSTAT files is available for the IBM-PC and compatibles; it includes a utility which converts ASCII data files to the SYSTAT/MYSTAT format. The FORTRAN 77 source code is available for those who would like to run BUMP on other machines. PMID- 2914425 TI - Pattern conserving data structure and algorithms for computations on dendritic trees. AB - The linked list is offered as a pattern conserving data structure, useful for storing neuronal dendritic trees. A BASIC language algorithm is described. Modifications of this algorithm for building linked lists, graphing dendritic trees, and tarry ordering trees are presented. Brief mention is made of the last in first out stack as a alternative data structure for computations on dendritic trees. PMID- 2914426 TI - A computer graphics program for measuring two- and three-dimensional form change in developing craniofacial cartilages using finite element methods. AB - Allometric analysis of chondrocranial growth seeks to provide objective measures of morphogenetic form change during ontogeny of the primordial skull. Linear measures, typically employed to study differential growth, become problematic at the histological level since an external referencing system is impossible to achieve for microscopic anatomies in embryos. The purpose of this paper is to describe a computer graphics program which generates spatially invariant measures of two- and three-dimensional form change using finite element methods. Anatomical form change is viewed as a continuous deformation of an initial finite element representing an anatomical unit into a second configuration. The algorithm consists of isoparametric scaling of finite elements, strain matrix formulation, and size/shape variable derivation. The routine includes four segments serving to extract nodal data, generate the strain matrix relating the two morphologies as well as deriving corresponding size/shape variables, reference the major and minor axes of form change, and provide graphic display of the anatomical geometries. Applications are provided measuring two- and three dimensional form change in the developing craniofacial cartilages of rats subjected to treatment with the known teratogen diazo-oxo-norleucine (DON). The finite element routine provides craniofacial form change variables which are expected in light of cellular alterations induced by DON administration. Finally, computational differences between this routine and similar approaches using finite element methods for analyzing biological form change are examined. PMID- 2914427 TI - Detection of the P and T waves in an ECG. AB - A method for the detection of the P and T waves, as well as the identification of their onset and offset boundaries in an ECG, is described in this paper. This method is based on a recently proposed "length" transformation, which exhibits some very interesting characteristics and can be utilized for one-channel or multichannel waveforms. The utilization of this transformation for the detection of the P and T waves in ECGs is exemplified in this paper. Experimental results are also given with real ECGs taken from the standard CSE ECG library. PMID- 2914428 TI - Preparing a medical informatics research grant proposal: general principles. PMID- 2914429 TI - Why is the USA the only country with compulsory cosmetic labeling? PMID- 2914430 TI - Topical cyclosporine: effects on allergic contact dermatitis in guinea pigs. AB - Cyclosporine (CSA) is an effective immunosuppressive agent and is used in tissue transplantation. The present investigation was undertaken to determine the effect of topical delivery of CSA on allergic contact dermatitis in guinea pigs. Topical 15% CSA in an azone (1-dodecylazacycloheptan-2-one)-containing vehicle blocked local elicitation in previously dinitrochlorobenzene (DNCB) sensitized animals that received a single topical application just prior to elicitation. Elicitation was not blocked at a distant site, indicating a local effect of topical CSA. In contrast, topical CSA when applied twice daily for a total of 5 applications during sensitization only, did not block subsequent elicitation. These experiments suggest that cyclosporine may be beneficial in the therapy of human contact dermatitis, as well as other T cell mediated dermatoses. PMID- 2914431 TI - Patch testing with nickel chloride in a hydrogel. AB - Various concentrations of NiCl2 in a hydrogel were evaluated as a possible alternative to the standard patch test material of 5% NiSO4 pet. Patch test responses were recorded on a total of 430 patients with known or suspected contact allergy. A NiCl2 concentration of 1% or less in the hydrogel failed to elicit a response in some patients who reacted to 5% NiSO4 pet. The 2% NiCl2 hydrogel produced a small increase in response frequency and may reduce false negative reactions. Along with the ability of the material to improve the topical bioavailability of nickel ions, more irritant reactions were observed. However, in cases with a positive history and a negative patch test with petrolatum, the hydrogel prepared from Methocel-E-4M seems to be a useful alternative vehicle for water-soluble allergens. PMID- 2914432 TI - The irritancy and allergenicity of 2-n-octyl-4-isothiazolin-3-one (Skane M-8), with recommendations for patch test concentration. AB - Preparations of 2-n-octyl-4-isothiazolin-3-one (Skane M-8) at 1000 p.p.m. a.i. and 500 p.p.m. a.i. in pet. induced allergy in a cumulative insult human patch test. Challenge patch testing using 250 p.p.m. a.i. Skane M-8 elicited allergy in 6 out of 6 sensitized individuals. Sensitized individuals did not cross react with Kathon biocide, (Kathon CG), a mixture of 5-chloro-2-methyl-4-isothiazolin-3 one and 2-methyl-4-isothiazolin-3-one. All pretrolatum preparations to which Tween 85 was added at 2.5% produced mild irritation in cumulative insult patch tests, but no irritation was observed with Tween 85 at 0.625%. We conclude that Skane M-8, 250 p.p.m. a.i. with Tween 85 0.625% in petrolatum is appropriate for patch testing for Skane M-8 allergy. PMID- 2914433 TI - Sensitization experiments with textile dyes in guinea pigs. AB - Experimental sensitization of guinea pigs with 6 azo and anthraquinone dyes used frequently as disperse dyes for fabrics (stockings, pantyhose) revealed that the blue dyes were moderate sensitizers while the red, yellow and orange dyes were only weak ones. This was found to be in contrast with the order based on the frequency of observed allergic sensitization, which showed the yellow and orange dyes at the top of the list and the blue dyes at the bottom. PMID- 2914434 TI - Immediate contact reactions to benzoic acid and the sodium salt of pyrrolidone carboxylic acid. Comparison of various skin sites. AB - Benzoic acid (BA) and the sodium salt of pyrrolidone carboxylic acid (NaPCA) were tested in 13 healthy persons to obtain information about, firstly, the irritant properties of NaPCA and, secondly, the reactivity of various skin sites. BA at 16, 8, and 4 mM pet., and NaPCA at 50, 25, 12.5, and 6.25% in water, were applied to the forehead, cheek, neck and upper back. Erythema reactions were observed visually, and the changes in the skin blood flow were monitored using a laser Doppler flowmeter. BA at 16 mM increased blood flow on the cheek of 12 test subjects, and on the neck, forehead and upper back of 6 subjects, but 8 and 4 mM BA elicited reactions only on the cheek. NaPCA caused reactions on the upper back of 3 test subjects only, but not on other test sites. PMID- 2914435 TI - Contact allergy due to colophony (III). Sensitizing potency of resin acids and some related products. AB - 7 resin acids, 3 synthetically prepared derivatives and the neutral fraction of Chinese colophony were studied by experimental sensitization using a modified FCA method. 4 resin acids, laevopimaric, abietic, podocarpic and tetrahydroabietic, proved to be weak sensitizers. Neoabietic, dehydroabietic, isopimaric acid and larixol remained negative. However, the derivatives, methyl abietate and calcium abietate, were shown to be moderate sensitizers, and the maleic-modified adduct to be a moderate to strong sensitizer. As laevopimaric acid plays only a minor role in colophony, abietic acid must be considered a major, even if weak, allergen in non-modified colophony. The neutral fraction of colophony is also partially involved in colophony allergy. PMID- 2914436 TI - A left versus right side comparative study of Epiquick patch test results in 100 consecutive patients. AB - 4 strips of 5 Epiquick patch tests (19 allergens plus 1 control) were applied symmetrically in duplicate on the left and right sides of the upper back in 100 consecutive patients. 70 positive allergic patch test reactions were recorded on the left side and 67 on the right side. 67 positive reactions were concordant on both sides (64 with the same score of intensity and 3 with a different score). 3 positive reactions (in 2 patients) on the left side were negative on the right side (1 TMTD, 1 cobalt chloride and 1 wool alcohols). At rechallenge 6 weeks later, they were positive. No explanation could be found for negative results at the first challenge on one side and not on the other. The rate of non reproducible positive results to the overall number of positive reactions was 4.2%. The good reproducibility rate (95.8%) provides useful information for further comparative studies. PMID- 2914437 TI - Contact urticaria from dog saliva. PMID- 2914438 TI - Contact urticaria from a chemical textile finish. PMID- 2914439 TI - Contact dermatitis from methyl methacrylate in an above-knee prosthesis. PMID- 2914440 TI - Contact dermatitis from methylionone fragrance. PMID- 2914441 TI - Contact allergy to Eusolex 8021. PMID- 2914442 TI - Risk of sensitization to Kathon CG. PMID- 2914443 TI - Admission of AIDS patients to a medical intensive care unit: causes and outcome. AB - As the number of cases of AIDS increases, it is important to determine whether ICUs can be productively and safely used for this patient population. From July 1981 to March 1987, 216 patients were admitted to the medical ICU: 166 (77%) were admitted for procedures and 50 (23%) were admitted for life-sustaining support. Most of the patients were admitted for respiratory failure (36 of 50), primarily as a result of Pneumocystis carinii pneumonia. Other patients were admitted for cardiovascular instability (six of 50 patients), CNS dysfunction (four patients), or other reasons (four patients). Of 50 patients admitted to the ICU, 13 (26%) were alive 3 months after hospital discharge. Despite 25 needle-stick injuries and 56 mucosal splashes involving human immunodeficiency virus (HIV)-infected patients and staff, no staff member converted HIV serology. These results suggest that AIDS patients may benefit from ICU admission. These patients appear to pose a low risk to the hospital staff in terms of occupationally acquired HIV infection, but strong emphasis needs to be placed on minimizing accidental exposures to potentially infected body fluids and to adhering to universal precautions. PMID- 2914444 TI - Cardiovascular, pulmonary, and renal effects of massively increased intra abdominal pressure in critically ill patients. AB - Massive elevation of intra-abdominal pressure (IAP) causes cardiovascular, respiratory, and renal dysfunction. We managed eight patients with high IAP (mean 51 +/- 7 cm H2O), six of whom had hemodynamic measurements; a clinical syndrome, characterized by hemodynamic, respiratory, and renal dysfunction, then became apparent. We report a) a baseline cardiopulmonary profile and response to an acute vascular volume challenge in six patients and b) surgical decompression of the abdomen in four patients. The clinical impression of hypovolemia was confused by small to normal left ventricular end-diastolic volume (64 +/- 14 ml) and normal ejection fraction (55 +/- 6%) despite very high right and left atrial filling pressures. Complete ventilatory support was necessary to maintain oxygenation and ventilation; oliguria (urine output less than 10 ml/h) was present. Pericardial effusion was absent. After fluid challenge (10 ml/kg of colloid or crystalloid infused iv over 10 min), filling pressures, cardiac output, and stroke volume all increased significantly (p less than .025) while heart rate decreased. Surgical decompression of the abdomen improved oxygenation, ventilation, cardiac output, atrial filling pressures, and urine output within 15 min. The cardiovascular effects of massively elevated IAP compounded by the requisite supportive care may require surgical relief. PMID- 2914445 TI - Decision not to treat: "do not resuscitate" order for the burn patient in the acute setting. AB - For some burn victims who are recognized early to be nonsurvivors, the decision to "make comfortable" is a treatment option. The guidelines for a "do not resuscitate" order must be based on an individual center's experience, but general principles can be formulated. PMID- 2914446 TI - Weaning from mechanical ventilation: adjunctive use of inspiratory muscle resistive training. AB - We used inspiratory resistive training (IRT) in an effort to improve the respiratory muscle endurance of 27 patients with respiratory failure who had failed repeated weaning attempts using standard techniques. Seven patients had primary neuromuscular diseases; the other 20 had primary lung diseases. All patients had stable respiratory failure, without gross malnutrition or electrolyte disorders. Their best initial T-piece duration averaged 6.4 +/- 8.4 (SD) h, with pHa 7.33 +/- 0.09 and PCO2 63 +/- 4 torr at the end of the T-piece trial. We provided a mean of five weekly training sessions of spontaneous breathing through an adjustable nonlinear resistor, with gradually increasing duration and resistance. When initial T-piece tolerance was less than 2 h, two to ten breaths of mechanical ventilation were provided during IRT sessions. No training session exceeded 30 min, and mechanical ventilation was provided between IRT sessions. Under this regimen, maximal inspiratory pressure improved from -37 +/- 15 to -46 +/- 15 cm H2O (p less than .001) and vital capacity improved from 561 +/- 325 to 901 +/- 480 ml (p less than .001). Twelve of the 27 patients were successfully weaned after 10 to 46 days; five more were weaned to nocturnal ventilation, for a total of 63%. We conclude that IRT can improve respiratory muscle strength and endurance in patients with respiratory failure, and can allow many of them to be weaned from mechanical ventilation. PMID- 2914448 TI - Organ blood flow and cardiovascular effects of high-frequency oscillation versus conventional ventilation in dogs with right heart failure. AB - Mongrel dogs underwent a large (apex to pulmonary valve) right ventriculotomy to produce right ventricular dysfunction. Right ventriculotomy decreased cardiac output from 2.47 +/- 0.43 to 1.34 +/- 0.16 L/min (p less than .01), increased CVP from 3.7 +/- 1.5 to 8.3 +/- 2.4 mm Hg (p less than .01), and decreased mean systemic arterial pressure (MAP) from 143 +/- 16 to 121 +/- 21 mm Hg (p less than .01). There was no effect on mean pulmonary artery pressure (MPAP) or pulmonary artery occlusion pressure. After stabilization a randomized crossover controlled comparison of conventional mechanical ventilation (CMV) and high-frequency oscillation (HFO) was performed. FIO2, pH, PCO2, core temperature, and preload were held constant. Mean airway pressure (Paw) was 4.8 +/- 0.7 cm H2O on CMV vs. 3.5 +/- 1.0 cm H2O on HFO (p less than .05). There was no difference in PaO2. We found no statistically significant differences between the two modes of ventilation with respect to cardiac output, MAP, MPAP, systemic vascular resistance, and pulmonary vascular resistance. Blood flows to cerebral cortex, renal cortex, adrenal, hepatic artery, left ventricular myocardium, and skeletal muscle were not different when comparing CMV to HFO. Despite the ability to attain equivalent oxygenation and ventilation at lower Paw, HFO offers no hemodynamic advantage over CMV in the presence of right ventricular dysfunction. PMID- 2914447 TI - Aminoglycoside pharmacokinetics: dosage requirements and nephrotoxicity in trauma patients. AB - We evaluated prospectively gentamicin and tobramycin pharmacokinetics in 37 patients with multiple system trauma and seven patients with isolated closed head trauma. The mean apparent volume of distribution (Vd) was 0.38 +/- 0.10 and 0.27 +/- 0.04 L/kg actual body weight (ABW) in patients with multiple trauma and closed head trauma, respectively. The difference in Vd between the two groups of patients was significant (p less than .002). Vd was not predictable on the basis of age, sex, weight, trauma score, or hospital day that therapy was initiated. Mean aminoglycoside clearance (Cl) was 123 +/- 46 ml/min. Neither serum creatinine nor estimated creatinine Cl predicted aminoglycoside Cl with sufficient accuracy to be clinically useful (r = .33 and .67, respectively). The mean daily dose was 6.1 +/- 1.6 mg/kg. The mean peak serum level was 5.8 +/- 1.3 micrograms/ml. Only one patient developed clinically significant renal dysfunction. Our data indicate that a loading dose of gentamicin or tobramycin of 3 mg/kg ABW in patients with multiple trauma and 2.5 mg/kg ABW in patients with isolated head trauma will obtain a mean initial peak serum level of 6.6 micrograms/ml. Although adequate maintenance dosing requires individualization based on pharmacokinetic analyses, large aminoglycoside doses can be used safely in patients with blunt trauma if appropriate monitoring is employed. PMID- 2914449 TI - Selective pulmonary vasodilatory effect of ZSY-27 in dogs with pulmonary hypertension due to pulmonary embolism. AB - The pulmonary vasodilator effect of ZSY-27, a newly synthesized phosphodiesterase inhibitor, was studied in dogs with pulmonary hypertension resulting from autologous muscle-induced pulmonary embolism (PE). A bolus injection of ZSY-27 (1 mg/kg) significantly decreased mean pulmonary arterial pressure from 32 +/- 4 to 24 +/- 5 mm Hg and pulmonary vascular resistance index from 415 +/- 60 to 316 +/- 94 dyne.sec/cm5.m2. ZSY-27 did not change mean arterial pressure. The cardiac index was slightly increased and the systemic vascular resistance index was slightly decreased after ZSY-27 injection, but these changes were not statistically significant. This study suggests that ZSY-27 is a possible therapeutic agent for pulmonary hypertension secondary to PE. PMID- 2914450 TI - Role of Fluosol-DA 20% in prehospital resuscitation. AB - Fluosol-DA 20% (FDA-20) resuscitation has been proposed for prehospital therapy of hemorrhagic shock (HS). Acute HS (mean arterial pressure 60 mm Hg X 90 min, then 40 mm Hg X 30 min) in 24 splenectomized dogs was treated with 50 ml/kg of lactated Ringer's solution (RL) plus a volume equal to 105% of shed blood volume of FDA-20 (group 1), FDA-20 carrier Annex solution (group 2), or RL (group 3). Cardiopulmonary, hemopoietic, hemodynamic, and organ function parameters were measured preshock, at the end of shock, and at 30 and 60 min, and 24 h after resuscitation. FDA-20 produced effective volume expansion, oxygen delivery, and oxygen consumption. The FDA-20 appeared to affect organ function and cells adversely as reflected by a fall in red cell mass and platelet levels and by a rise in liver enzymes, BUN, and serum creatinine. Both the FDA-20 and Annex solution led to a reduction in serum proteins including serum albumin, serum globulin, immunoglobulin-G, and fibrinogen. These reductions are probably due to an oncotically driven factor which appears to maintain an optimal lymph to plasma oncotic ratio. The hydroxyethyl starch in the FDA-20 and the Annex solution, thus, would drive the plasma proteins into the interstitial space. The prolonged prothrombin times and the activated partial thromboplastin times after FDA-20 may be due, in part, to a reduction in the coagulation proteins, although these were not measured. Pending further studies designed to assess the effects of FDA-20 on possible cellular and multiple organ toxicity, clinical studies are premature and unwarranted. PMID- 2914451 TI - New pigtail catheter for pleural drainage in pediatric patients. AB - The conventional method of pleural drainage is tube thoracotomy, accomplished by chest wall dissection and blunt puncture. While this method is successful, it is relatively traumatic. We have designed a pigtail catheter which may be inserted into the pleural space by a modified Seldinger technique. This 8.5-Fr polyurethane catheter has six side ports inside its circular distal end. An airtight plastic bag is attached to the insertion needle to confirm pleural placement. Nineteen catheters were inserted in 16 neonates and small children with either pneumothorax or pneumomediastinum. No complications were noted. All but one pneumothorax was successfully evacuated; however, the pneumomediastinum reaccumulated. Insertion proved to be safe, simple, and atraumatic. This pigtail pleural drainage catheter provides an alternative to standard tube thoracotomy. PMID- 2914452 TI - Comparison of two formulas to calculate alveolar oxygen tension in canine oleic acid pulmonary edema. AB - Alveolar oxygen tension (PAO2) is calculated by either of two mathematical formulas incorporating various respiratory variables. The first formula, Equation 1, assumes a constant RQ of 0.8; the second formula, Equation 2, uses the mixing equation and requires analysis of inspired, mixed expired, and end-tidal gas samples. We tested the consistency of these formulas before and after asymmetric oleic acid pulmonary edema, then calculated and compared venous admixture values using the PAO2 value derived from each formula. Before oleic acid, Equations 1 and 2 were similar (213 +/- 22 vs. 211 +/- 22 [SD] torr, respectively), as were venous admixture values (8.7 +/- 2.9% vs. 8.5 +/- 2.9%, respectively). After oleic acid injury, Equation 1 was significantly lower than Equation 2, thus slightly but consistently underestimating venous admixture (29.9 +/- 12.2% vs. 30.2 +/- 12.3%; p less than .01). However, the venous admixture values obtained after oleic acid injury calculated from Equations 1 and 2 correlated closely (r2 = .998; p less than .001), and the clinical differences yielded by the two formulas would be minimal. We recommend using the simpler formula (Eq. 1) when calculating PAO2. PMID- 2914453 TI - Low dose norepinephrine in patients with septic shock and oliguria: effects on afterload, urine flow, and oxygen transport. PMID- 2914454 TI - Bretylium intoxication resembling clinical brain death. PMID- 2914455 TI - Adverse effects of sublingual nifedipine in acute myocardial infarction. PMID- 2914456 TI - Tongue-tied in the burn intensive care unit. PMID- 2914457 TI - Patient controlled anxiolysis with midazolam. PMID- 2914458 TI - Balloon dislodgment: a complication of attempted pulmonary artery catheterization. PMID- 2914460 TI - Cytotoxic effector mechanisms. PMID- 2914459 TI - Use of an ultrathin fiberoptic catheter for neonatal endotracheal tube problem diagnosis. PMID- 2914461 TI - Contact urticaria from chlorhexidine. PMID- 2914462 TI - Cutaneous sinus of dental origin: a diagnosis requiring clinical and radiologic correlation. AB - Cutaneous sinuses may arise from chronic dental infections. These sinus tracts usually appear as suppurative lesions of the chin or neck. Diagnosis is made by palpating the lesion and by radiologic examination demonstrating periapical dental abscess. Treatment with dental extraction or root canal results in resorption of the inflammatory fistula. Since many patients with sinus tracts of dental origin do not have any complaints of tooth or mouth pain, the correct diagnosis may be overlooked by the unsuspecting clinician. PMID- 2914463 TI - Silent bowel perforation occurring during corticosteroid treatment for pemphigus vulgaris. AB - We present the case of a patient who experienced a silent colonic perforation while being treated for pemphigus vulgaris with prednisone and azathioprine. Dermatologists are experienced in the management of pemphigus vulgaris with prednisone. We report a well-recognized but rarely reported adverse effect of this standard therapy for pemphigus vulgaris. PMID- 2914464 TI - Asymmetrical growth of scalp hair in syringomyelia. AB - Trophic alterations in the skin take place consequent to interruption of its motor, sensory, and autonomic innervation. The hair in denervated areas is often less abundant and grows more slowly. Syringomyelia is a common cause of cutaneous trophic alterations that are often unilateral. They occur predominantly in the upper extremities and seldom involve the skin over the face and scalp. A patient with syringomyelia exhibited a unilateral impairment of pain and temperature sensation in the entire right side of the scalp. A dissimilarity of hair length between the right and left side of the scalp was noticed, with a sharp demarcation along the midline. This peculiar trophic change has not been previously described in the medical literature. PMID- 2914465 TI - Fuchs' heterochromic iridocyclitis. AB - A 32-year-old man with Fuchs' heterochromic iridocyclitis is described, and a review of the pertinent medical literature is presented. PMID- 2914466 TI - Three vignettes about modern health care. PMID- 2914467 TI - Tinea versicolor of the face in black children in a temperate region. AB - Tinea versicolor is a common superficial fungal infection that typically affects young adults in warm, humid climates. We describe two young black children in the temperate northeastern Ohio area with tinea versicolor limited to the face. The occurrence of tinea versicolor on the face is unusual, as is its appearance before puberty. The mycologic and pathophysiologic characteristics of tinea versicolor infection are discussed, and several hypothesis are offered to explain the presence of tinea versicolor in these patients. PMID- 2914469 TI - Interpretation of the serum magnesium level. PMID- 2914468 TI - Cell kinetics of the inflammatory reaction. Papers from a symposium. Sundvolden, Norway, September 1987. PMID- 2914470 TI - Intravenous dipyridamole infusion causes severe bronchospasm in asthmatic patients. PMID- 2914471 TI - Withholding life support. An ethical guide for the perplexed. PMID- 2914472 TI - Evaluation of conventional circulatory assist devices. Intraaortic balloon pumping, venoarterial bypass, and extracorporeal membrane oxygenation. AB - This study was undertaken to reveal the limitations and problems with the conventional mechanical circulatory assist devices by analyzing the results in 70 cases; intraaortic balloon pumping (IABP group, n = 42), venoarterial bypass pumping (VAB group, n = 18), and extracorporeal membrane oxygenation (ECMO group, n = 10). The IABP could significantly prevent the development of postoperative low cardiac output state, and the best survival rate (62 percent) was obtained in the coronary arterial disease group. In the VAB group, eight (44 percent) cases were weaned, and four (22 percent) cases survived. These conventional assist devices could, though with limitations, certainly support the circulation and/or provide a period for it to recover, otherwise bridging the patients to new methods. The early decision not only for initiation of mechanical assist devices but also for moving to more definite procedures will improve the results with such devices. PMID- 2914473 TI - Submaximal invasive exercise testing and quantitative lung scanning in the evaluation for tolerance of lung resection. AB - Lung resection in patients with cardiopulmonary dysfunction is associated with increased risk. We studied 52 elderly male patients with airflow obstruction and a lung mass. Studies were performed at rest with routine ventilatory tests and lung scan quantitation of right-left lung function. Cycle ergometry exercise was then performed at 2 submaximal work loads (25 and 40 watts). Data were obtained using systemic and pulmonary artery catheterization for blood pressures, thermal dilution cardiac output, and blood gases. Twenty-nine patients underwent lung resection and seven failed to tolerate the procedure (death within 60 days or prolonged ventilator dependence). Those parameters most clearly separating the group tolerating surgery (n = 22) from the intolerant group (n = 7) were obtained during exercise and included: cardiac index (tolerant 5.5 +/- 1.3 vs intolerant 3.9 +/- 0.3 L/min/m2, p less than .01), O2 delivery (p less than .01) and calculated VO2 ml/kg/min (tolerant 11.3 +/- 2.1 vs intolerant 7.8 +/- 1.5 ml/kg/min, p less than .001). Pulmonary vascular pressures and calculated resistance did not predict intolerance. Calculated VO2 at 40 watts did not separate those patients who had survivable complications from those who did not (p much greater than .05). Multivariate analysis suggests that exercise VO2 is an important predictor of tolerance of lung resection because it reflects the effects of cardiac function and O2 transport. In our patients with COPD, submaximal exercise testing predicted intolerance of lung resection better than calculation using quantitative lung scanning. Exercise testing may accomplish this goal by uncovering deficits in O2 transport. PMID- 2914474 TI - Nocturnal oxygen therapy does not improve snorers' intelligence. AB - STUDY OBJECTIVE: To determine whether nasal oxygen therapy at 2 L/min would (1) reverse nocturnal hypoxemia and (2) improve neuropsychologic function in men who snore heavily. DESIGN: To select heavy-snoring subjects for a treatment protocol, volunteers were screened for one night, breathing air the first half and oxygen the second half of the night. If nocturnal oxygen desaturation occurred in the first half and was improved in the second half of the night, the subject entered a two-month treatment program. In random order, either nocturnal air or nocturnal oxygen was administered for one month each at 2 L/min in a double-blind crossover design. Neuropsychologic testing was done before and after each month. SETTING: Oxygen concentrators were modified to produce either greater than 96 percent oxygen or air at 2 L/min. Machines were delivered to the home of the subject and the machines were used each night, administering inspirate by nasal cannula. PARTICIPANTS: Seventeen asymptomatic men who snored heavily and volunteered for minimal payment of $75. INTERVENTIONS: Air was administered for one month, and oxygen was administered for one month. MEASUREMENTS AND RESULTS: On the screening night, oxygen administration did not improve obstructive sleep apnea, but did improve oxygenation. After one month of oxygen therapy at night, there was no significant benefit to multiple measures of neuropsychologic function. CONCLUSION: In this study, oxygen therapy at night had no effect on neuropsychologic function in men who snore heavily. PMID- 2914475 TI - Intracranial pressure and obstructive sleep apnea. AB - In order to describe variation in AP and ICP during OSA, six patients with severe OSA were examined, with determination of ICP, AP, CVP, respiration, tcPO2, tcPCO2, and nocturnal sleep polygraphy. During apnea, elevations of AP and ICP were observed, related to the apneic episodes. The elevations in pressure were only observed in relation to apneic episodes. While awake, none of the patients showed pressure elevations. There were highly significant correlations between duration of apnea and variation in AP and ICP and between variations in AP and ICP. Values for ICP while awake were above normal (greater than 15 mm Hg; intracranial hypertension) in four of six patients. Morning ICP was higher than evening ICP. Systolic, mean, and diastolic ICP and AP increased during sleep above awake values. The ICP increased during NREM stages 1 to 4, and the highest values were observed during REM sleep. Vascular response was not changed during REM sleep, and the higher ICP during REM could solely be explained by the longer apneas during REM sleep. The CPP decreased during apnea. PMID- 2914476 TI - Acute inferior vena cava thrombosis. Early results of heparin therapy. AB - STUDY OBJECTIVE: To determine, during heparin therapy, the embolic risk associated with acute inferior vena cava thrombosis compared with noncaval thrombosis. DESIGN: Prospective controlled study. SETTING: University-affiliated general hospital. PATIENTS: Of 68 consecutive patients considered, 18 with cavographically proved inferior vena cava thrombosis and 45 with phlebography proved noncaval proximal thrombosis met all other eligibility criteria and completed the study. INTERVENTIONS: All patients received adjusted continuous IV heparin therapy for ten days. MEASUREMENTS AND RESULTS: All 63 patients underwent systematic baseline and "day 10" perfusion lung scanning and phlebocavography. None suffered pulmonary embolism within the ten days, but 11/63 patients showed thrombus extension on day 10 phlebocavograms. Retrospectively, no significant difference could be found between the groups with and without extension. CONCLUSIONS: (a) The early embolic risk associated with heparin-treated venous thromboses appears low and does not seem to depend on the location (caval or more peripheral) of venous clots. (b) Thrombus extension may occur in spite of apparently "adequate" anticoagulation with heparin. PMID- 2914477 TI - Acute ventricular septal rupture. Angiographic-morphologic features and clinical assessment. AB - Twenty patients with acute ventricular septal rupture underwent cardiac catheterization. Prior to catheterization, 17 patients were in Killip class 3-4. Mean cardiac index and cardiac output were 2.03 +/- 0.81 L/min/m2 and 3.55 +/- 1.33 L/min, respectively. Based on a recent pathologic description of septal rupture, we encountered by angiography and during surgery, two morphologic types of rupture: simple type which appears as a direct through-and-through communication between the ventricles, and complex type which presents hemorrhagic tracts in the septum with the opening into the ventricles at different levels. Considering the management of patients with septal rupture and the clinical outcome in our series, it is suggested that there is a need to minimize invasive angiographic procedures prior to early surgical correction of the ruptured septum. PMID- 2914478 TI - Safety and efficacy of using high-dose topical and nebulized anesthesia to obtain endobronchial cultures. AB - We evaluated the safety and efficacy of high-dose topical and nebulized airway anesthesia in normal volunteers and in patients undergoing diagnostic fiberoptic bronchoscopy. Lidocaine solution (4 percent) was used for gargling, for spraying the palate and oropharynx with an atomizer, and for nebulization with an air powered nebulizer (mean total dose, 1,682 mg) and 2 percent lidocaine (Xylocaine) jelly for anesthetizing nasal passages. In six normal subjects and in eight patients, lidocaine blood levels were measured at baseline, after gargling, after spraying, after nebulization, and then at 5, 10, 15, 30, and 60 min; 19 normal subjects and ten patients underwent the same anesthesia protocol but had no blood drawn. Fiberoptic bronchoscopy was performed in 21 normal volunteers and in 18 patients and cultures obtained using the protected specimen brush. Additional endobronchial lidocaine (mean 256 mg) was given to the 18 patients after collecting the microbiology specimens. Peak lidocaine blood levels remained below 6 micrograms/ml in all cases. Cough and discomfort during bronchoscopic examination was absent or minimal in 17 of 21 normal subjects (80 percent) and in 14 of 18 patients (77 percent) and was severe in only one instance (5 percent). There were no related complications. Using only topical and nebulized anesthesia is safe and effective for performing fiberoptic bronchoscopy, especially when bacterial cultures are to be obtained and endobronchial instillation of lidocaine must be avoided. PMID- 2914479 TI - Diagnosis of peripheral lung cancer in cases of tumors 2 cm or less in size. AB - This study evaluates the results of preoperative diagnosis on 108 resected cases of peripheral lung cancer with a tumor size of 2 cm or less. Transbronchofiberscopic curettage was performed in 85 cases under x-ray TV fluoroscopy. Only 65 of 85 patients were positive on the initial bronchoscopy (76.5 percent), with repeated bronchoscopy, and 71 of 85 were positive for malignant cells (83.5 percent). The cases for which diagnosis could not be obtained with curettage were those in which the tumor shadow was not visible by x ray TV fluoroscopy, those in which the lesions arose extramurally compressing the bronchi, or in cases of subpleural lesions. Curettage did not yield a diagnosis in cases with lesions less than 1.1 cm. In cases of small lung cancer lesions, peripheral transbronchofiberscopic curettage should be expected to yield a false negative rate of approximately 15 percent. Therefore, even when the results of curettage are negative, further detailed examinations including needle biopsy, are necessary to obtain a definitive diagnosis. PMID- 2914480 TI - Clinical relevance of the interaction of theophylline with diltiazem or nifedipine. AB - The results of previously published studies indicate that calcium channel blockers are capable of competitively inhibiting cytochrome P-450 activity in hepatic microsomes, the pathway of theophylline metabolism. In addition, case reports have suggested that theophylline serum concentrations change when a calcium channel blocker has been added to or deleted from a stable theophylline regimen. To determine the clinical relevance of this potential interaction in patients with chronic asthma, we measured a peak steady-state theophylline serum concentration in 21 subjects while receiving theophylline alone (400 to 1,500 mg/day), and again, at least seven days later, after the addition of continuous therapy with maximally tolerated doses of either diltiazem (n = 18) or nifedipine (n = 16). The diltiazem dose was increased in 120 mg/day increments, as tolerated, to a maximum of 240 to 480 mg/day, while the nifedipine dose was increased in increments of 40 mg/day, to a maximum dose of 80 to 160 mg/day. The mean +/- SEM theophylline serum concentrations were 13.6 +/- 1.4 micrograms/ml before and 14.0 +/- 1.2 micrograms/ml during concurrent diltiazem therapy, and 12.6 +/- 1.0 micrograms/ml before and 12.2 +/- 1.1 micrograms/ml during nifedipine (p greater than 0.05). With this sample size there is a 5 percent chance that we missed a 20 percent change in serum concentration (type II error). Thus, maximum tolerated doses of diltiazem or nifedipine do not impair the metabolism of theophylline to a clinically relevant degree and adjustment of theophylline dosage is not required after the addition or discontinuation of diltiazem or nifedipine. In addition, these data suggest that currently available in vitro techniques for evaluating drug interactions in the hepatocyte do not predict the clinical relevance of such an interaction in patients who might require both drugs for different therapeutic indications. PMID- 2914481 TI - Prednisone pretreatment leads to histaminic airway hyporeactivity soon after resolution of the immediate allergic response. AB - We assessed the effect of prednisone pretreatment (50 mg/day for three days) on the development of the early increase in histamine reactivity that occurs soon after resolution of the immediate response in allergic humans. Four allergic subjects who were known to develop only isolated immediate responses upon Kentucky bluegrass inhalation, as well as four mild allergic asthmatic subjects known to develop typical dual phase responses, were evaluated. All testing was done more than nine weeks after the grass pollen season had ended. Allergen inhalation produced an immediate response in all subjects. However, upon resolution of the immediate response to allergen in these pretreated subjects, the PC200His in all dual responding asthmatics and in three of the four isolated immediate responders had substantially increased above baseline values. We conclude that prednisone pretreatment leads to histaminic hyporeactivity soon after resolution of the immediate allergic response in both dual responding asthmatics and isolated immediate responders. It would seem that this prednisone effect is independent of its potential influence on the influx of inflammatory cells into diseased airways. PMID- 2914482 TI - Survival time of patients with pleural metastatic carcinoma predicted by glucose and pH studies. AB - STUDY OBJECTIVE: To determine the survival time of patients with pleural metastatic carcinoma diagnosed by thoracoscopy, as related to the pleural glucose and pH levels, and to the extension of pleural neoplastic lesions. DESIGN: Cohort analytic prospective study. Follow-up of the patients from diagnostic thoracoscopy to death (range: one to 29 months). SETTING: Referral Pneumology Service at a Tertiary Care Center. PATIENTS: Consecutive sample of 50 patients with pleural metastatic carcinoma diagnosed by thoracoscopy. Three patients were lost in the follow-up. INTERVENTIONS: Talc pleurodesis was performed after diagnosis and with the same technique in every case. MEASUREMENTS AND RESULTS: In all the cases, the extension of the tumorous lesions was determined by thoracoscopy (classified on a scale from 0 to 9) and the survival time was studied from the time that thoracoscopic diagnosis was made. On the same or the previous day as the exploration, blood and pleural fluid glucose levels as well as arterial and pleural pH and gas tensions were determined. PMID- 2914483 TI - Pulmonary hypertension due to toxic oil syndrome. A clinicopathologic study. AB - Clinical and pathologic findings in seven patients who died of severe pulmonary artery hypertension due to toxic oil syndrome are assessed. These cases correspond to a late stage of evolution of the disease characterized by progressive deterioration in clinical features--increasing dyspnea, chest pain, syncope, and death (in low-output heart failure). The main pathologic pulmonary vascular findings consisted of plexiform lesions, thromboses, and venous lesions. Endothelial damage induced by the toxic agents is suggested as an initial causative mechanism, perpetuated by intimal proliferation and in situ thrombosis. Plexiform lesions appear late and active histologically. This new cause of pulmonary artery hypertension, with pathologic findings similar to those found in primary pulmonary hypertension, may help in understanding the pathophysiology of this unknown disease. PMID- 2914484 TI - Prospective study of a standardized questionnaire to improve clinical estimate of pulmonary embolism. AB - A standardized questionnaire was administered to 100 patients suspected of having pulmonary embolism to investigate whether clinical data may be reliably used in the decision-making process of such patients. Questionnaire data were compared with lung scintigraphy outcome and 16 variables were selected as significantly associated with the scintigraphic diagnosis. Based on these variables, patients with abnormal scintigraphy compatible with pulmonary embolism and patients with scintigraphy not compatible with embolism were classified in accordance with the scintigraphic diagnosis. When these 16 variables were tested in an additional validation group, clinical and scintigraphic diagnosis matched in most cases. These results show that clinical data can be used to predict the outcome of lung perfusion scintigraphy in patients suspected of pulmonary embolism. Use of a standardized questionnaire can improve the accuracy of pretest assessment of such patients and positively influence the decisions to start heparin coverage or obtain pulmonary angiography. PMID- 2914485 TI - Transmural pressure measurements. Importance in the assessment of pulmonary hypertension in obstructive sleep apneas. AB - Seven patients with OSAS were studied during nocturnal sleep in order to assess the trend of PAP throughout apneas and to identify factors possibly associated with such a trend. All patients underwent a polysomnography including the monitoring of PAP and esophageal pressure. While intravascular PAP decreased during apneas and increased at the resumption of breathing, transmural PAP values (ie, corrected for intrathoracic pressure swings) showed a trend toward a progressive increase throughout apneas and toward a decrease once ventilation had been resumed. The measurement of transmural values allowed a reliable assessment of PAP changes occurring during apneas, and different degrees of such changes shown by different patients may be related to a host of factors relevant to wakefulness and sleep, including individual responsivity to hypoxic stimulus. PMID- 2914486 TI - The quality of well-being in cystic fibrosis. AB - Traditional outcome measures in CF include PFTs, exercise tests, and several scoring systems that depend on pulmonary status and are largely subjective. The Quality of Well-being scale (QWB) is a widely used tool for measuring quality of life by three subscales: mobility, physical activity, and social activity, with points assigned within each subscale. The QWB has been shown to be valid in patients with COPD. We administered the QWB scale to 44 patients with CF, aged 7 to 36 years, and examined the relationship between QWB and PFTs, and in 15 patients the QWB vs exercise performance (peak VO2) on a progressive cycle ergometer test. QWB was significantly correlated with each variable examined: QWB vs FEV1, r = 0.5518 (p less than .0001); QWB vs FEF25-75%, r = 0.4793 (p less than .001); QWB vs PEFR, r = 0.4018 (p less than .01); QWB vs peak VO2, r = 0.5778 (p less than .01). The QWB scale is an objective measure that is significantly correlated with measures of performance and pulmonary function in CF. The relationship is not one of identity; further, the QWB is broad based and takes into account general well-being, not just pulmonary health, adding an important dimension to the care of patients with CF. PMID- 2914487 TI - Unconjugated pteridines in bronchoalveolar lavage as indicators of alveolar macrophage activation. AB - Bronchoalveolar lavage (BAL) has shown great efficacy in clarifying the role of immune processes in many disorders of the lower respiratory tract. Following the in vitro demonstration that neopterin is an indicator of the activation of macrophages, neopterin was measured in the BAL fluid and cells from patients with various pulmonary diseases. In most of the patients, high levels of neopterin were found in the serum, BAL fluid and BAL cells. Because neopterin in BAL fluid results from local production as well as from plasma transudation, neopterin in BAL cells seems to reflect the macrophage stimulation more directly. In addition, the correlation between cellular neopterin and lymphocyte count was found to be more significant than the correlation between cellular neopterin and macrophage count. Neopterin in BAL fluid and cells may be a useful measurement in the investigation and elucidation of pulmonary pathologies involving the cellular immune system. PMID- 2914488 TI - Single-chamber cardiac pacing with two forms of respiration-controlled rate responsive pacemaker. AB - Ventilatory changes correlate with the heart rate response during exercise, and such changes have been used to determine an appropriate chronotropic response in the Biorate (RDP3 and MB-1) and Meta pacemakers, both of which use a thoracic impedance measurement principle. Ten patients with the Biorate and 11 patients with the Meta were studied. In both groups, significant rate response and improvement in exercise duration compared with fixed rate ventricular pacing were achieved during symptom-limited treadmill exercise tests, with good correlations between the pacing rate and estimated oxygen consumption. Motion artefacts affected the measured impedance of both pacemakers, with rate response occurring during arm movements in the absence of respiratory activity. This observation suggested that both pacemakers have the potential of activity sensing. The earlier version of the Biorate (RDP3) was limited by myopotential interference, and erosion of the auxiliary lead can be problematic in some patients. PMID- 2914489 TI - Left ventricular dysfunction in symptomatic mitral valve prolapse. AB - Idiopathic MVP is characterized by a late systolic click or murmur from myxomatous mitral valvular dysfunction. It may be complicated by atypical chest pain, ventricular arrhythmias, and ECG changes that can mimic the symptoms of coronary artery disease. We prospectively performed radionuclide cineangiograms before and after stress tests in MVP patients with chest pain compared with asymptomatic MVP patients and symptomatic normal control patients. In ten patients with MVP, chest pain, and normal coronary anatomy, the LVEF remained essentially unchanged (increase of -0.5 +/- 4 percent) after exercise. In ten patients with MVP and no chest pain and in nine with normal cardiovascular system and chest pain, the exercise LVEF increased by 11.5 +/- 2 percent (p less than 0.05) and 17.4 +/- 3 percent (p less than 0.005), respectively. The resting LVEF was significantly lower (p less than 0.02) in the symptomatic MVP patients (59 +/ 3 percent) than in the asymptomatic MVP (76 +/- 5 percent) or symptomatic normal patient control subjects (70 +/- 3 percent). Patients with MVP and chest pain had a lower resting LVEF and an abnormal left ventricular functional response to exercise compared with asymptomatic MVP patients or symptomatic normal subjects. Therefore, exercise radionuclide ventriculography may not adequately differentiate between chest pain due to MVP or coronary artery disease. PMID- 2914490 TI - Surgical transsternal treatment of bronchopleural fistula postpneumonectomy. AB - An original method of treatment for main bronchus fistula occurring after pneumonectomy was described in 1961. The operation is performed via a median sternotomy and the carinal region exposed. The main bronchi can then be divided in an area not involved with infection. We describe ten patients who underwent this procedure. The left bronchus was divided in seven patients and the right in three. Nine patients were long-term survivors, and one patient died in the early postoperative period from myocardial infarction. The transmediastinal approach for the control of bronchopleural fistula seems an effective means of managing this difficult postoperative problem. PMID- 2914491 TI - Acute myocardial infarction after heart irradiation in young patients with Hodgkin's disease. AB - Forty-seven patients younger than 40 years at the time of the diagnosis, and irradiated to the mediastinum for Hodgkin's disease at Turku University Central Hospital from 1977 to 1982, were regularly followed for 56 to 127 months after therapy. Two patients developed an acute myocardial infarction ten and 50 months after cardiac irradiation at the age of only 28 and 24 years, respectively. None of the patients died from lymphoma within five years from the diagnosis, but one of the infarctions was eventually fatal. Since acute myocardial infarction is rare in this age group, the result suggests strongly that prior cardiac irradiation is a risk factor for acute myocardial infarction. The possibility of radiation-induced myocardial infarction should be taken into account both in treatment planning and follow-up of patients with Hodgkin's disease. PMID- 2914492 TI - Hypomagnesemia in patients in postoperative intensive care. AB - In order to study the clinical consequences of postoperative hypomagnesemia, the serum magnesium (Mg) concentration was measured in samples of blood collected from 193 patients admitted to two postoperative ICUs. On admission to the ICU, 117 patients (61 percent) had hypomagnesemia (serum Mg less than 1.5 mEq/dl), 66 patients (34 percent) had normomagnesemia (1.5 to 2.0 mEq/dl), and ten patients (5 percent) had hypermagnesemia (greater than 2.0 mEq/dl). There were no correlations between the severity of illness score (r = 0.145) or the degree of hypoproteinemia (r = 0.01) and the postoperative serum Mg level. Patients with severe hypomagnesemia (serum Mg less than or equal to 1.0 mEq/dl) experienced hypokalemia more often (p less than 0.02) than the others in the study. Furthermore, those with severe hypomagnesemia had a higher mortality rate (7/17 or 41 percent) than the remainder of the population studied (22/176 or 13 percent) (p less than 0.02). Those with severe hypomagnesemia had received aminoglycosides more often (p less than 0.001) than those with normal serum Mg concentrations. The serum Mg level was not a sensitive (68 percent) or specific (37 percent) predictor of survival. Our conclusions were as follows: (1) hypomagnesemia is common in postoperative ICU patients; and (2) patients in the postoperative ICU who have severe hypomagnesemia have a higher mortality and more hypokalemia than similarly ill patients with normomagnesemia. Because of the association between aminoglycoside therapy and severe hypomagnesemia, we recommend measurement of this variable in those patients receiving aminoglycosides. Furthermore, Mg replacement therapy is recommended for those patients with serum Mg values of 1 mEq/dl or less. PMID- 2914493 TI - Determinants of weaning and survival among patients with COPD who require mechanical ventilation for acute respiratory failure. AB - The decision to institute MV in patients with COPD and ARF is difficult because the risk of complications is high and the long-term prognosis is poor. We reviewed our experience with 95 COPD patients with ARF requiring MV. Fifty-five patients required MV for more than two weeks, 72 were weaned successfully, and 59 died within one year of follow-up. Survival was associated with premorbid level of activity (p less than .001), FEV1 (p less than .01), serum albumin level (p less than .05), and severity of dyspnea (p less than .01). Cor pulmonale on ECG, premorbid hypercarbia, and history of left ventricular failure were also more common among those who died. Weaning from MV was associated with premorbid level of activity (p less than .001), FEV1 (p less than .001), albumin level (p less than .05), and negative inspiratory pressure (p less than .001) and respiratory rate during T-piece trial (p less than .01). The duration of intubation was associated only with premorbid level of activity (p less than .01). Predictive models for the weaning success and the one-year survival were developed. PMID- 2914494 TI - Catheter balloon valvuloplasty treatment of adult patients with mitral stenosis. PMID- 2914495 TI - Respiratory management after cardiac surgery. PMID- 2914496 TI - Roentgenogram of the month. A middle-aged man with a right upper lobe mass. Rounded atelectasis of the right upper lobe with bilateral pleural thickening. PMID- 2914497 TI - Bradycardia-dependent bundle branch block during Mobitz I second degree heart block. PMID- 2914498 TI - Cavitary lung disease with skin lesions. PMID- 2914499 TI - Massive tracheal necrosis complicating endotracheal intubation. AB - There are significant complications associated with endotracheal intubation. Massive tracheal necrosis secondary to tracheoesophageal space abscess developed in a 71-year-old man during mechanical ventilation. Elevated endotracheal tube cuff pressures, sepsis, hypotension, and other risk factors predispose to this disastrous consequence. PMID- 2914500 TI - A rare endobronchial neurilemmoma (Schwannoma). AB - Primary neurogenic tumors of the lung are rare. Often, their histologic behavior presents a treatment dilemma. We present a case of benign endobronchial neurilemmoma managed by means of YAG laser resection together with a brief discussion of the management options available for these tumors. PMID- 2914501 TI - Rapid development of cor pulmonale following acute tonsillitis in adults. AB - We describe two adult patients in whom acute tonsillitis resulted in the rapid development of cor pulmonale in the absence of clinically evident upper airway obstruction or diffuse obstructive airway disease. Both patients had developed symptoms of sleep apnea and all-night polysomnography confirmed the presence of severe obstructive sleep apnea. These cases emphasize the potentially severe cardiovascular consequences of acute tonsillar hypertrophy in the obese adult patient. PMID- 2914502 TI - Bilateral exudative pleural effusions following intravenous ethchlorvynol administration. AB - A 26-year-old man had bilateral alveolar infiltrates and exudative pleural effusions following self-administration of intravenous ethchlorvynol (ECV). The effusions and pulmonary edema resolved by 72 h with supportive therapy only. As no other etiology was established, we concluded that the pathogenesis of the pleural fluid was the transvisceral pleural leak of the increased extravascular lung water induced by ECV. Current experimental and clinical evidence support the concept that pleural effusions probably develop in most states of permeability pulmonary edema. PMID- 2914503 TI - Pulmonary alveolar proteinosis. Occurrence with metastatic melanoma to lung. AB - Pulmonary alveolar proteinosis is characterized by excessive accumulation of surfactant-like material in the alveoli, resulting in part from defective alveolar clearance by macrophages. We present a case of alveolar proteinosis in a patient with malignant melanoma metastatic to lung and discuss possible alteration in macrophage function in the pathogenesis of these two concomitant processes. PMID- 2914504 TI - Subaortic stenosis by solitary rhabdomyoma. Successful excision in an infant following 2D echocardiogram and Doppler diagnosis. AB - A seven-month-old girl had subaortic stenosis caused by a single intracavitary rhabdomyoma unassociated with tuberous sclerosis. Diagnosis was formulated on the basis of two-dimensional echocardiography and Doppler technique findings alone, and surgery was successful. PMID- 2914505 TI - Effect of temporary external stabilization on ventilator weaning after sternal resection. AB - The role of mechanical fixation of the chest wall in the treatment of flail chest remains controversial. We report a case of flail chest resulting from major sternal resection. The application of a temporary external stabilization device improved pulmonary mechanics by decreasing the respiratory rate from 36/min to 10/min while increasing tidal volume and vital capacity from 140 +/- 85 ml and 195 +/- 90 ml, respectively, to 450 +/- 110 ml and 905 +/- 310 ml, respectively. The improvement with the temporary device facilitated weaning from mechanical ventilation. We recommend consideration of this technique in selected cases of flail chest resulting from major chest wall resection. PMID- 2914506 TI - Chest trauma and subvalvular left ventricular aneurysms. AB - Two patients were discovered to have pulsatile saccular lesions at the base of the left ventricle and mitral regurgitation following blunt trauma to the chest. These aneurysms resembled annular subvalvular aneurysms which have previously been reported as congenital defects in African blacks and as acquired lesions following endocarditis or mitral valve replacement. The first patient had two aneurysms, while the second had an aneurysm in continuity with a traumatic ventricular septal defect. These aneurysms were detected by echocardiography and magnetic resonance imaging and should be sought in patients who develop valvar regurgitation following chest trauma. PMID- 2914507 TI - Airway complications from free-basing cocaine. AB - The majority of the deaths due to fires result from smoke inhalation, hypoxia, and systemic toxicity. Lower airway injury from chemical byproducts carried in the smoke is less frequent and thermal injury to the lower airways is a rare occurrence. We report a case of severe thermal injury to the conducting airways due to either inhalational injury or to intratracheal ignition of the ether vehicle used in free-basing cocaine resulting in severe reactive airways disease and tracheal stenosis requiring reconstructive surgery. PMID- 2914508 TI - Calcified right atrial myxoma demonstrated by magnetic resonance imaging. AB - Cardiac myxoma of the right atrium was diagnosed in a 64-year-old woman by use of MRI. With the MRI technique, an absence of signal intensity was shown within parts of the tumor, indicating the presence of intratumoral calcification. The MRI also demonstrated an intratumoral area of high signal intensity which was related to the presence of hemorrhage within the tumor. Both MRI findings were confirmed on pathologic examination of the surgical specimen. Magnetic resonance imaging may be a useful test to evaluate the heart for mass lesions in those patients in whom echocardiography is inadequate. PMID- 2914509 TI - Acute pulmonary edema associated with the use of oral ritodrine for premature labor. AB - We describe a patient who developed acute pulmonary edema while taking oral ritodrine for the treatment of premature labor and recovered after its discontinuation. The mechanism of development of pulmonary edema associated with beta-sympathomimetic agents is still not fully understood. Patients taking oral ritodrine should be observed for cardiopulmonary signs and symptoms. PMID- 2914510 TI - Assessing the work of breathing. PMID- 2914511 TI - The role of transthoracic needle biopsy. PMID- 2914512 TI - The cost of lavage. PMID- 2914513 TI - Pneumomediastinum or auto-PEEP? PMID- 2914514 TI - The newest quinolone antibacterial agents and theophylline. PMID- 2914515 TI - 2nd ACCP Conference on Antithrombotic Therapy. American College of Chest Physicians. June 21, 1988. Proceedings. PMID- 2914516 TI - Rules of evidence and clinical recommendations on the use of antithrombotic agents. PMID- 2914517 TI - Living in the war zone: mothers and young children in a public housing development. AB - This paper explores how mothers who live in two Chicago neighborhoods share the possibility of real danger with their preschool children. A structured interview was conducted with 20 mothers: ten who live in a high-rise public housing development and ten residents of a nearby community. The initial findings raise critical questions for those concerned with mental health issues in child development. PMID- 2914519 TI - A comprehensive program for pregnant adolescents: parenting and prevention. AB - Beginning in 1981 as an effort to reduce mortality rates of at-risk infants, the Teen Pregnancy Project of this agency has grown steadily into a multiservice program with many approaches, yet all services for its help-resistant population depend upon an outreach, home-visiting initiative to establish useful relationships with its clients. PMID- 2914518 TI - Pregnant teens: differential pregnancy resolution and treatment implications. AB - Profiles on three groups of pregnant teens in a comprehensive social service agency were identified: those who followed through with a parenting plan, those who followed through with an adoption plan, and those who switched from an adoption plan to a parenting plan. Pregnant teens who switched plans were identified as high risk in terms of health histories and psychosocial profiles. Since they represent as much as one-third of the total population, service plans must be made for them that focus on these risk areas. This article addresses the identification of new subgroups in the universe of pregnant teenagers, and treatment implications. PMID- 2914520 TI - Training mental health practitioners to work with adoptive families who seek help. AB - The lack of appropriate therapeutic resources for adoptive children and their adoptive families who seek treatment is a national problem. The mental health community has failed to recognize the specific knowledge and expertise that therapists must have if they are to help this population. This article describes the initiative taken by one organization to attack this problem in its state. PMID- 2914521 TI - Caring for day care: a pilot project. AB - Day care in Israel is not always of high quality, and the current forecast for upgrading the standards of the existing centers is bleak, due to economic and social factors that do not place high priority on quality infant care in group settings. The agency attempted, therefore, to develop a low-cost, efficient method of early intervention, wherein skilled social workers were hired, given special training, and worked alongside the caregivers of day care centers to help children and parents defined as at risk. This article describes the observations that were made and the interventions that were chosen. PMID- 2914522 TI - Resection and sutured peranal anastomosis for carcinoma of the rectum. AB - Resection and peranal suture is now an accepted technique for low rectal carcinoma; however, long-term results of large numbers are not known. Eighty-four patients who had this procedure at a specialist institution between 1972 and 1985 are reviewed. There was a low operative mortality (2.4 percent), but a high complication rate with pelvic sepsis in 34 (40.5 percent) and anastomotic dehiscence (either partial or complete) in 40 (47.6 percent). The crude five-year survival rate was 56 percent. Isolated local recurrence occurred in seven patients (9.2 percent) and in a further seven patients it was associated with systemic recurrence. The functional results were satisfactory with 92 percent of assessed patients having three or less bowel actions per day. Subsequent incontinence occurred in 8 of the 60 patients assessed and 5 of these needed proximal diversion. For patients in whom the only alternative is abdominoperineal excision of the rectum, these results confirm that there is no disadvantage in terms of potential cure and that the functional results are acceptable. PMID- 2914523 TI - Age and sex distribution of patients with colorectal cancer. AB - A retrospective review of 922 colorectal cancer patients was undertaken to determine whether the nonuniform anatomic distribution of colorectal cancer was influenced by age and/or sex. The mean age of patients with right colon lesions (71.2 years) was significantly higher than for either patients with left colon lesions (68.2 years) or rectal lesions (65.6 years). Further analysis disclosed that patients with proximal tumors were older than patients with distal tumors primarily because of the later presentation of females with cecal or ascending colon cancers. Comparison of the anatomic distribution of tumors in patient groups above and below the age of 70 revealed that right colon cancers accounted for a greater percentage of colorectal tumors in the older patient group than in the younger patient group. These findings support the roles played by both age and sex in influencing colorectal cancer location. Furthermore, these data provide a plausible explanation for the increasing incidence of proximal colonic lesions. PMID- 2914524 TI - The external anal sphincter. Relationship between anal manometry and anal electromyography and its clinical relevance. AB - Anal manometry and anal electromyography (EMG) were performed in 45 patients to evaluate the external anal sphincter. Their symptoms were soiling (N = 6), incontinence (N = 10), and obstipation (N = 19). Clinical diagnoses were previous anal surgery (N = 16), rectal prolapse--partial, total, intussusception (N = 16), puborectalis syndrome (N = 4), neurologic disorders (N = 3), and others (N = 6). The relationship between the maximum squeeze pressure (MSP) measured with anal manometry and the maximum (voluntary) contraction pattern (MCP) and signs of denervation (DEN) measured with anal EMG were examined. The correlation coefficient between MSP and MCP was 0.55 (P less than .001) and between MSP and DEN 0.13 (NS). A normal MSP always showed a normal MCP, a normal MCP showed an abnormal MSP in 43 percent only. In conclusion, the clinical value of anal EMG seems limited. Assessment of an additional anal EMG seems indicated in incontinent patients with previous anal surgery with a low MSP to estimate muscle function, whenever anal surgery is considered. Anal EMG during straining can easily confirm the clinical diagnosis of puborectalis syndrome. PMID- 2914525 TI - Perforating and nonperforating Crohn's disease. An unpredictable guide to recurrence after surgery. AB - Four hundred eighty-six patients who have had resections for Crohn's disease at the Cleveland Clinic were reviewed. The patients were categorized by indication for surgery into three groups: perforating (P) (135 patients), nonperforating (NP) (278 patients), and miscellaneous (M) (77) patients. One hundred ninety-four patients had two or more resections and 56 underwent a third resection. Patients were no more likely to have the same indication for surgery at the time of the second resection (P = 25 percent; NP = 44 percent; M = 57 percent) or the third resection (P = 11 percent; NP = 65 percent; M = 55 percent). There was also no difference in the interval between resections for the P and NP groups. The lack of agreement between resections suggests that the categorization of patients into P and NP groups does not facilitate prediction of the nature of recurrent disease. The concept of aggressive perforating and indolent nonperforating Crohn's is not substantiated by this study. PMID- 2914526 TI - An analysis of survival and voiding, sexual function after wide iliopelvic lymphadenectomy in patients with carcinoma of the rectum, compared with conventional lymphadenectomy. AB - Records of four hundred thirty-seven patients with lower and middle rectal cancer who underwent resection for cure at National Cancer Center Hospital from 1969 to 1983 were reviewed. There were significantly lower recurrence rates in the extended excision group compared with the conventional excision group. The recurrence rates between these two groups with Dukes' A were 0 percent (0 of 23) vs. 5.2 percent (5 of 96), those with Dukes' B were 6.3 percent (5 of 80) vs. 21.9 percent (14 of 64), Dukes' C were 23.6 percent (20 of 89) vs. 32.8 percent (28 of 85). The differences between the two groups with Dukes' B and C were statistically significant (P less than .05). The cumulative five-year survival rates in the extended excision group were 94 percent with Dukes' A stage, 88 percent with Dukes' B stage, and 61 percent with Dukes' C stage, compared with 91 percent (Dukes' A), 74 percent (Dukes' B), and 43 percent (Dukes' C) in the conventional excision group. There were also statistically significant differences between the two groups with Dukes' B and C stages (P less than .05). Although wide iliopelvic lymphadenectomy was successful as far as decreasing the incidence of local recurrence and also in prolonging survival, there were increased incidences of urine-voiding failure (loss of sense of bladder being full of urine detected in 39.4 percent of the extended excision group vs. 8.8 percent of the conventional excision group) and sexual impotency (76 percent vs. 37.5 percent). PMID- 2914527 TI - Treatment of patients with rectal cancer. AB - During a 20-year period (1965 to 1985), 4673 patients with rectal cancer underwent surgical treatment, with 3500 of them being subjected to radical surgery. Postoperative mortality was 6.1 percent. During the last five years, the mortality rate decreased dramatically down to 4.9 percent, despite an increase in the group of elderly patients (35.7 percent) and performance of a considerable percentage of simultaneous, extensive, and combined operations (33.7 percent). The trend of employing sphincter-saving operations (in more than 60 percent of patients, the anterior resection and abdominoanal resection with a pull-through were performed) accounts for the favorable five-year survival rate (62 to 69 percent) and results in a good functional outcome in 80 percent of patients. The use of a combination of conservative and operative methods of rehabilitation contributes to the professional readaptation of 75 to 80 percent of patients after surgery with construction of a stoma. In 223 cases, a Soviet magnetic occlusive device was implanted, while in 67 patients an artificial sphincter mechanism was constructed from the flap of the adductor longus femoris muscle. It should be emphasized that surgical methods of rehabilitation are used both in primary and reconstructive operations. The experience with management of 124 patients with recurrent cancer after resection and extirpation of the rectum shows that local excision or repeated resections of the rectum cure 20 to 29 percent of those operated on. PMID- 2914528 TI - Massive gangrene of the colon--a complication of fecal impaction. Report of a case. AB - A case of extensive gangrene of the colon secondary to fecal impaction is reported. The role of ischemia in the management of colonic obstruction and the pathogenesis and treatment of colonic gangrene are discussed. PMID- 2914529 TI - Recurrent squamous-cell carcinoma arising in pilonidal sinus tract--multiple flap reconstructions. Report of a case. AB - Squamous-cell carcinoma arising from a pilonidal sinus tract is an unusual complication of a common condition. Approximately 36 cases of carcinoma related to pilonidal disease have been reported in the literature. Wide excision with tumor-free margins has yielded five-year disease-free states in 55 percent of patients. Recurrence rates have been 44 percent to 50 percent in several large series. Regional (inguinal) nodal metastasis occurs in 14 percent of patients, heralding a dismal prognosis. Radiation and chemotherapy are of minimal palliative value. Reconstruction of these patients has consisted of split thickness skin grafts or local cutaneous and myocutaneous flaps. Some authors have allowed healing by secondary intention. A case of squamous-cell carcinoma arising in a chronic pilonidal sinus tract is reported. Local recurrence required an extensive resection resulting in a large sacral/perineal defect. A single stage reconstruction of this defect with multiple muscle and musculocutaneous flaps is described. PMID- 2914530 TI - Colopleural fistula presenting as tension pneumothorax in strangulated diaphragmatic hernia. Report of a case. AB - A case of colopleural fistula, resulting from strangulation and perforation of a diaphragmatic hernia and presenting as tension pneumothorax, is reported. The hernia was most likely a consequence of a stab wound to the left side of the chest four years before admittance. Colopleural fistula as a cause of tension pneumothorax is an extremely rare entity, reported only once in past English medical literature. PMID- 2914531 TI - Use of thoracoabdominal incision for cancer of the splenic flexure in the obese patient. AB - The thoracoabdominal incision is not a common incision in colonic surgery. However, it may be of unique benefit in tumors of the splenic flexure in which adequate mobilization and adequate lateral resection margins may otherwise be difficult to achieve. These tumors are believed to carry a poorer prognosis in part because of reduced accessibility. Specifically, exposure in short, obese patients with locally advanced lesions may be improved significantly with a thoracoabdominal incision. This report presents a patient with a tumor of the splenic flexure invading the diaphragm, greater curvature of the stomach, splenic hilum, and tail of the pancreas. The exposure provided by this incision made a radical cancer operation possible, which would not have been possible with an abdominal incision. PMID- 2914532 TI - Finger clubbing, inflammatory bowel disease, and circulant vasodilators. PMID- 2914533 TI - Reflections. PMID- 2914534 TI - Effect of sucralfate on experimental colitis in the rat. AB - The therapeutic effect of sucralfate on ulcerated gastric and duodenal mucosa is well known. There is, however, almost no information about its activity in colitis. Experimental colitis was produced in rats by rectal instillation of 1 ml of 10 percent acetic acid, and 1.5 ml of a 20 percent suspension of sucralfate was then administered every 12 hours for various lengths of time. Study animals and appropriate controls were killed after 3, 7, 10, or 14 days. The distal colons were studied macroscopically and histologically. Colonic prostaglandin E2 levels were measured in animals killed after 3, 7, 10, or 14 days. The macroscopic score was significantly improved 10 and 14 days after induction of colitis, although the histologic appearance was unchanged. Acetic acid administration increased and sucralfate treatment reduced prostaglandin E2 levels in colitic animals on days 3 and 7, but not later. The present study supports a role for sucralfate in the treatment of colitis, but further studies on the mechanism of its effect and on its clinical activity are indicated. PMID- 2914535 TI - Elevated gastrin levels in patients with colon cancer or adenomatous polyps. AB - Gastrin has been shown to stimulate the growth of carcinogenic-induced colon cancer in animals, and some human colon cancers grown in vitro or as xenografts in nude mice. We determined fasting plasma gastrin levels in control subjects and patients with adenomatous polyps or adenocarcinoma of the colon to determine whether abnormal levels occurred in either patient group. Blood samples were obtained from 73 patients undergoing colonoscopy, primarily for evaluation of Hemoccult-positive stools. Fasting plasma gastrin was significantly greater in patients with adenomatous polyps (24.2 +/- 5.7 pM, N = 25) or colon cancer (84.5 +/- 28.5 pM, N = 20) than in controls (9.9 +/- 0.9 pM, N = 28). Elevations were due to gastrin values greater than control mean + 2 SD in nine patients with polyps (19.5-150.2 pM) and eight with cancer (20.7-403.2 pM). None of the patients had identifiable causes (drugs, prior surgery) for elevated gastrin levels. Our results indicate that elevated plasma gastrin occurs in subgroups of patients with adenomatous polyps or adenocarcinoma of the colon. The cause and potential role of elevated gastrin for polyp and tumor growth in these patients is not known. PMID- 2914536 TI - Immune-related alterations in aged gut-associated lymphoid tissues in mice. AB - To study whether senescence-induced changes in the gut-associated lymphoid tissue (GALT) are mainly quantitative, several parameters were examined in three age groups of BALB/c mice (1-2, 12-14, and 24-28 months old). A substantial senescence-associated decline in the number of lymphoid cells was found in the mesenteric lymph nodes (MLN) and spleen (SPN), and especially in the Peyer's patches (PP), but not in the lamina propria (LP). The distribution of lymphocyte subsets in these tissues was also altered with an absolute reduction of T cells- in particular, a L3T4+ helper/inducer T-cell marker-bearing subset. These changes were most remarkable in PP, followed by MLN. The in vitro proliferative reactivity and the production of each isotype-specific immunoglobulin (Ig) by PP, MLN, and SPN were profoundly affected when T-cell-dependent (Td) B-cell mitogens were used, but minimally affected when T-cell-independent (Ti) B-cell mitogens were used. The isotype-specific Ig content of small-intestinal perfusates was also influenced by aging, but only to a minor extent, as exemplified by a decrease in IgA levels in the fasting condition. Thus, despite the defects in the quantity and distribution of lymphocytes in aged PP and MLN, the finding of little change in the total amount of secreted IgA in aged intestine suggests that gut IgA-mediated luminal immune responses could remain nearly unaltered with senescence. The constancy of intraluminal IgA levels could be of physiological significance in host defense at the gut mucosal surface in aged mice. PMID- 2914538 TI - Cerebral responses evoked by electrical stimulation of rectosigmoid in normal subjects. AB - We used electroencephalographic methods to evoke and record cerebral responses to electrical stimulation of the rectosigmoid colon in eight healthy male volunteers, 20-40 years old. The stimulus was applied via a probe equipped with bipolar ring electrodes which were attached by suction to the mucosa. The probe was positioned 20 cm above the anus. Cerebral responses were recorded by EEG electrodes. Evoked potentials (EPs) in response to electrical stimulation consisted of a series of successive peaks and troughs in the EEG with good reproducibility within and between subjects. The shape and latencies of the intestinal EPs were comparable to other types of EPs reported before. It is concluded that reproducible EPs can be recorded from the scalp after electrical stimulation of the rectosigmoid. The similarity in appearance of these EPs to those previously reported suggests that visceral afferents were stimulated. The technique may become a useful tool to study visceral nervous connections to the brain in health and disease. PMID- 2914537 TI - Loss of absorptive capacity for sodium chloride as a cause of diarrhea following partial ileal and right colon resection. AB - Previous studies have emphasized the role of bile acid and fat malabsorption as the cause of the diarrhea that may follow ileal and right colon resection; unabsorbed bile acids and fat are believed to reduce sodium chloride and water absorption in the remaining colon. In this paper we report studies in eight patients with severe postresection diarrhea, in search of a more basic defect in sodium chloride absorption, ie, a loss of sodium chloride absorptive capacity as a direct consequence of resection of sodium chloride absorption sites. First, we determined whether or not diarrhea persisted during a 48-hr fast; in all patients diarrhea and large fecal electrolyte losses continued during a fast. Second, we measured sodium chloride and water absorption rates during total gut perfusion with a balanced electrolyte solution; compared to normal controls, the patients absorbed 23-31% less water, sodium, and chloride. In three patients who could be studied further, the absorptive defect was markedly accentuated when the perfusing solution was such that sodium chloride absorption had to take place against a concentration gradient. These observations indicate that postresection diarrhea patients have a reduced capacity to absorb sodium chloride, particularly when there is a concentration gradient between lumen and plasma. Although all of these patients had malabsorption of radiolabeled taurocholic acid, there was only a modest and statistically insignificant reduction in daily stool weight during treatment with large doses of cholestyramine, suggesting that bile acid malabsorption was not responsible for a major part of their diarrhea.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2914539 TI - Effects of enteric neural stimulation on chloride transport in human left colon in vitro. AB - Nonpathological segments of muscle-stripped left colon from patients undergoing surgery for carcinoma, diverticulitis, or other causes were set up in flux chambers in order to determine the influence of intrinsic neurons on ion transport. In the basal state, both sodium and chloride were actively absorbed, and there was no significant residual ion flux. Electrical field stimulation of the intrinsic mucosal innervation evoked an increase in short-circuit current that was dependent on stimulus frequency and strength. The response was mimicked by scorpion venom, which is known to depolarize neurons, and was nearly abolished by tetrodotoxin, which prevents neurotransmitter release. Atropine reduced, but did not abolish, the response to neural stimulation. Carbachol, aminophylline, and theophylline significantly increased short-circuit current above basal levels. Electrical field stimulation evoked an increase in short-circuit current that could be accounted for by a decrease in net chloride absorption without any significant effect on sodium absorption or residual ion flux. These results suggest that ion transport in the human left colon is regulated by intrinsic submucosal cholinergic neurons as well as other neuronal types, and activation of these nerves could provide the basis for certain diarrheal disorders. PMID- 2914540 TI - Effects of sennosides on colonic myoelectrical activity in man. AB - The effects of sennosides on colonic myoelectrical activity were investigated in man. Spiking activity of the left and sigmoid colons was continuously recorded in seven constipated patients during two sessions from 5:00 PM to 9:00 AM. Each patient received orally at 7:00 PM on two consecutive days 30 mg of sennosides one day (sequence S) and placebo on the other (sequence P) in a random fashion. A significant (P less than 0.05) increase of peristaltic activity (migrating long spike bursts or MLSBs) after sennosides was observed between 1:00 and 7:00 AM, and a corresponding decrease between 7:00 and 9:00 AM. No change was noted in total short spike burst (SSB) activity or in SSBs characteristic of the rectosigmoid area. This study indicates that the main modification of colonic motility induced by sennosides was a stimulation of propulsive activity (MLSBs), which occurred between 6-12 hr after oral administration, the delay required for orocecal transit and metabolism of the drug. PMID- 2914541 TI - Different innervation mechanisms between the lesser and greater curvature of guinea pig antrum. AB - Transmural stimulation (TS) produced a frequency-dependent contraction of the longitudinal muscles from the lesser curvature of the guinea pig antrum, which was abolished by atropine. On the other hand, a response to TS of the strips from the greater curvature was biphasic: a rapid contraction followed by a relaxation, which was abolished by tetrodotoxin. By pretreatment with atropine, rapid contraction of the biphasic response evoked by TS in the greater curvature was abolished and relaxation was augmented. Relaxation to TS of the greater curvature was not affected by prazocine, yohimbine, phentolamine, propranolol, theophylline, apamin, alpha-chymotrypsin, and vasoactive intestinal polypeptide receptor antagonist. Different innervation mechanisms were suggested to be present in the longitudinal muscles between the lesser curvature (innervated with excitatory cholinergic neurons) and the greater curvature (innervated with excitatory cholinergic neurons and nonadrenergic inhibitory neurons) of the guinea pig antrum. PMID- 2914542 TI - Impaired oxygenation of gastric mucosa in portal hypertension. The basis for increased susceptibility to injury. AB - Increased susceptibility to mucosal damage is a prominent feature of portal hypertensive gastropathy. Since the portal hypertensive gastric mucosa has extensive microvascular changes, we postulated that the increased sensitivity to mucosal damage could have an ischemic basis. We measured distribution of gastric serosal and mucosal oxygenation in a group of portal hypertensive and sham operated rats, and then studied the effects of intragastric aspirin. In the basal state, gastric mucosa of portal hypertensive rats had significantly reduced oxygenation compared to controls (24 +/- 5 vs 45 +/- 7 mm Hg PO2, P less than 0.02), while serosal oxygenation was similar between the two groups. Intragastric aspirin produced significantly greater mucosal damage to portal hypertensive rats and mucosal oxygenation was almost one third that of sham-operated controls. Systemic arterial pressures and oxygenation were similar between the two groups. We conclude that there is impairment of gastric mucosal oxygenation and increased mucosal damage by aspirin in portal hypertensive rats compared with sham-operated controls. These results support our hypothesis that the increased sensitivity of the portal hypertensive mucosa to damage is a consequence of impaired mucosal oxygenation. PMID- 2914543 TI - Salicylsalicylic acid causes less gastroduodenal mucosal damage than enteric coated aspirin. An endoscopic comparison. AB - The gastroduodenal mucosal damage caused by aspirin and nonsteroidal antiinflammatory drugs is a common clinical problem. We compared two medications designed to diminish mucosal damage: enteric-coated aspirin and salicylsalicylic acid (salsalate). Ten healthy volunteers were randomized to receive either 1.5 g salsalate twice a day or 650 mg enteric-coated aspirin four times a day for six days and were then crossed over to the other drug after a one-week medication free period. Endoscopic inspection of gastroduodenal mucosa was performed at entry and again after six days of drug therapy for each medicine. Mean serum salicylate concentrations taken before the morning drug dose were 11.2 mg/dl for enteric-coated aspirin and 18.1 mg/dl for salsalate. Only one of 10 subjects receiving salsalate developed mild (grade 1) mucosal damage while six of 10 receiving enteric-coated aspirin developed moderate to severe damage (grade 2-3) (P = 0.01). Symptoms were mild in both groups. We conclude that salsalate causes less gastroduodenal mucosal damage than enteric-coated aspirin. PMID- 2914544 TI - Refractory duodenal ulcers (nonhealing duodenal ulcers with standard doses of antisecretory medication). AB - To evaluate possible differences between patients with refractory duodenal ulcers and those with duodenal ulcers that respond to standard doses of antisecretory medications, we determined basal acid outputs by nasogastric suction and daily smoking histories in 75 patients with endoscopically documented active duodenal ulcers. Patients were treated for at least eight weeks with standard doses of antisecretory medications and endoscopic healing or nonhealing was documented. Fifty-five patients that had complete healing of their duodenal ulcers had a mean basal acid output of 6.6 +/- 5.3 meq/hr, and 18/55 had daily cigarette smoking histories, whereas 20 patients that had nonhealing duodenal ulcers had a mean basal acid output of 20.0 +/- 9.6 meq/hr, and 8/20 had daily cigarette smoking histories. There were no significant differences between the two groups with regard to age, duodenal ulcer size, or cigarette smoking history. However, there were significant differences in male-female ratio (P less than 0.02) and in mean basal acid output (P less than 0.001), and all patients with nonhealing duodenal ulcers had basal acid outputs of greater than 10.0 meq/hr. Patients with nonhealing duodenal ulcers were treated with increased doses of ranitidine, mean 675 mg/day (range 600-1200 mg/day), and all had complete healing endoscopically documented. These results indicate that patients treated with standard doses of antisecretory medications with nonhealing duodenal ulcers have increased basal acid outputs of greater than 10.0 meq/hr, and the duodenal ulcers heal with increased doses of antisecretory medication. PMID- 2914545 TI - Effects of mepirizole and basic antiinflammatory drugs on HCl-ethanol-induced gastric lesions in rats. AB - Mepirozole, a basic antiinflammatory drug and duodenal ulcerogen in laboratory animals, macroscopically protected the gastric mucosa of rats from HCl-ethanol induced damage in a dose-dependent manner. These effects were evident when the agent was given orally, intraperitoneally, or subcutaneously at 3 or 10 mg/kg 0.5 hr before HCl-ethanol administration. Histologically, the surface epithelial and pit cells were not protected by mepirizole, but most of the mucosal cells located in the deeper portions were well preserved. Gastric acid secretion in the pylorus ligated or acute fistula preparation was not affected by 10 mg/kg of mepirizole. Gastric motility determined by a balloon method was dose-dependently inhibited by the agent. Mepirizole protection was significantly reduced by pretreatment with subcutaneous indomethacin (5 mg/kg) and N-ethylmaleimide (10 mg/kg). The gastric motility inhibited by mepirizole was not reversed by indomethacin and N ethylmaleimide treatment. These results suggest that the mechanism underlying mepirizole protection relates to both endogenous prostaglandins and sulfhydryl compounds present in the gastric mucosa, but does not relate to an inhibition of gastric motility. Dulcerozine and other basic antiinflammatory drugs (tiaramide, tinoridine, and benzydamine) given either orally or intraperitoneally at 10-100 mg/kg also dose-dependently prevented the development of HCl-ethanol-induced lesions. Mepirizole and other basic antiinflammatory drugs are cytoprotective in the rat stomach. PMID- 2914546 TI - Basal gastric acid secretion in nonulcer dyspepsia with or without duodenitis. AB - Nonulcer dyspepsia with or without duodenitis and duodenal ulcer disease are often considered to be a spectrum of the same acid-peptic process. Some reports evaluating basal gastric acid secretion in nonulcer dyspepsia and duodenal ulcer disease have supported that impression; however, results from different studies have been mixed. In order to compare basal gastric secretory profiles in nonulcer dyspepsia and duodenal ulcer disease, we determined basal acid outputs in 66 consecutive patients with the diagnosis of nonulcer dyspepsia. All patients with nonulcer dyspepsia had at least a three-month history of epigastric abdominal pain, and all had negative upper gastrointestinal endoscopies except for 14 with duodenitis. The 66 patients with nonulcer dyspepsia were compared to 40 asymptomatic normal subjects and 114 patients with endoscopically documented duodenal ulcer disease. There was no significant difference in mean basal acid output among all 66 patients with nonulcer dyspepsia (2.9 +/- 2.7 meq/hr), the group of normal subjects (3.2 +/- 2.7 meq/hr), the 14 patients with nonulcer dyspepsia with duodenitis (3.0 +/- 2.1 meq/hr), and the 52 patients with nonulcer dyspepsia without duodenitis (2.9 +/- 2.9 meq/hr). However, mean basal acid output of the patients with duodenal ulcer disease (9.1 +/- 7.6 meq/hr) was significantly higher than all the other groups (P less than 0.001). The gastric acid secretory profiles determined in this study do not appear to support the view that nonulcer dyspepsia with or without duodenitis and duodenal ulcer disease are a spectrum of the same acid-peptide process. PMID- 2914547 TI - Gastric acid secretion and gastric emptying of liquids in 99 male duodenal ulcer patients. AB - Gastric acid hypersecretion and accelerated gastric emptying are commonly considered as possible determinants of duodenal ulcer, but the relative frequencies of these gastric dysfunctions have never been evaluated in a homogeneous group of patients. We studied basal and pentagastrin-stimulated gastric acid secretion and gastric emptying of a radiolabeled caloric liquid meal in 99 consecutive male patients with endoscopically proven, active, uncomplicated duodenal ulcers. Compared to matched healthy subjects, ulcer patients presented increased basal and stimulated acid secretion (P less than 0.001). Sixty-nine patients had peak acid output values above the 95% confidence limits of the control population (14.2-30.6 meq/hr). Cigarette smoking was correlated with gastric acid hypersecretion. No significant difference was found between duodenal ulcer patients and controls in mean gastric emptying times. Ulcer patients showed a greater variance of gastric acid secretion and emptying values than healthy subjects. This reflects varied gastrointestinal function among ulcer patients. No significant correlation was found between gastric acid output and gastric emptying times. These findings suggest that gastric acid hypersecretion, but not accelerated gastric emptying of liquids, play a relevant role in the pathogenesis of duodenal ulcer. PMID- 2914548 TI - Postprandial disruption of migrating myoelectric complex in dogs. Hormonal versus extrinsic nervous factors. AB - Our aim was to determine the mechanism whereby the jejunoileum regulates postprandial gastroduodenal motility. Five dogs were prepared with a proximal jejunal infusion catheter and with gastric manometry catheters and serosal intestinal electrodes for recording gastric and intestinal motility. After two weeks, fasted dogs were studied during jejunal infusion of either isosmolar NaCl (154 mM) or isosmolar mixed nutrient solution (50% Meritene) on four separate days each. After completion of these baseline studies, the dogs underwent a model of autotransplantation of the entire jejunoileum (extrinsic denervation, disruption of intrinsic neural continuity with proximal duodenum). Two weeks later, identical studies as before were repeated with the now "autotransplanted" jejunoileum. Before transplantation, infusion of NaCl did not interrupt the characteristic interdigestive migrating motor complex either in the gastroduodenum or in the jejunoileum. However, infusion of nutrients interrupted the migrating motor complex both in the gastroduodenum and jejunoileum for the duration of the infusion (5 hr). After autotransplantation of the jejunoileum, the migrating motor complex continued to occur in the gastroduodenum and in the jejunoileum during infusion of NaCl, but the migrating motor complex cycled independently in each region without any temporal coordination. Jejunal infusion of nutrients interrupted the MMC in both regions for the duration of infusion (5 hr). Because inhibition of the gastroduodenal and jejunoileal migrating motor complex continued to occur during infusion of nutrients into the transplanted jejunum, we concluded that jejunoileal regulation of postprandial inhibition of interdigestive motility in the stomach and duodenum is mediated by hormonal factors and does not require intrinsic neural continuity. PMID- 2914549 TI - Isolated granulomatous gastritis in an adolescent. AB - This is a case of a 14 1/2-year-old black male with isolated granulomatous gastritis. The case is unusual in several aspects. For the first time this disorder has been seen in the pediatric age group. The symptoms and signs were more acute and severe than previously reported, and the inflammatory process involved the entire gastric mucosa. Several findings suggested an (auto)immune pathogenesis. The patient had a good clinical and histologic response to prednisone therapy, but the disease recurred after two years when therapy was discontinued. PMID- 2914551 TI - Increase in ornithine decarboxylase activity associated with development of dysplasia in Barrett's esophagus. AB - A case of Barrett's esophagus of the specialized columnar type is described in which mucosal ornithine decarboxylase levels were measured in endoscopic biopsies at two intervals over which severe dysplasia had developed. The Barrett's mucosa extended 5 cm above the gastroesophageal junction, was free of dysplasia, and had no detectable ornithine decarboxylase activity at initial evaluation. On follow up endoscopy one year later, the Barrett's mucosa had become dysplastic with a markedly elevated ornithine decarboxylase activity of 1.56 units/mg protein. The patient underwent an esophagectomy because of persistent severe dysplasia and continues to do well postoperatively. Elevated ornithine decarboxylase activity has been described in other premalignant conditions, especially when dysplasia has been present. Further studies in Barrett's esophagus are warranted, since ODC activity might prove to be a useful biochemical marker for dysplasia and increased cancer risk. PMID- 2914550 TI - Barrett's mucosa of distal esophagus with concomitant isolated Crohn's disease and intramucosal adenocarcinoma. Report of a case and analysis of the literature. AB - The presence in the esophagus of three distinct entities--Barrett's mucosa, Crohn's disease, and adenocarcinoma--is a very rare finding. In a 60-year-old man with a long history of heartburn and recently developed dysphagia, narrowing of the distal esophagus was found to be related to the presence of Barrett's mucosa. A short time later repeated endoscopy revealed adenocarcinoma in this area. The patient underwent esophagogastrectomy and died a few days after surgery. Findings in the surgical specimen and upon autopsy were consistent with isolated Crohn's disease of the distal esophagus as well as with intramucosal adenocarcinoma. Analysis of the data available in the literature reveals that Crohn's disease of the esophagus, although rare, clearly possesses some definite characteristics of its own. It is suggested that the presence of these three features in a single patient constitutes no more than a chance coexistence. PMID- 2914552 TI - Transnasal biliary drainage for treatment of common bile duct leakage and bile peritonitis. AB - A new nonoperative method for treating postoperative common bile duct leaks by endoscopic placement of a nasobiliary stent is described. Two patients were treated successfully by placing a nasobiliary stent above the point of bile leakage, acting to divert the flow of bile and to allow the fistula to close. PMID- 2914554 TI - [Cauda equina syndrome in ankylosing spondylitis]. AB - A 55-year-old man who has had ankylosing spondylitis for over 20 years developed gradually increasing pain and sensory disorders in the legs, as well as mild foot and toe elevator weakness. There was no evidence of inflammatory activity. Clinical, neurophysiological and neuroradiological examination revealed a cauda equina syndrome as a late complication of ankylosing spondylitis. There is no known causal treatment. PMID- 2914553 TI - [Air transportation of patients: a danger of hypoxic organ lesions?]. AB - As illustrated by two cases, a fall in alveolar oxygen pressure at high altitude, such as during transportation by plane, can cause hypoxic pulmonary failure, especially in patients with already impaired pulmonary or circulatory functions. Arterial oxygen saturation was recorded by pulse oximetry in 14 healthy volunteers and eight patients during air transportation. Oxygen saturation decreased with reduced cabin pressure. Decreased saturation for each 100 mm Hg reduction in cabin pressure was markedly greater in the patients than the healthy volunteers. Pulmonary and circulatory status should be assessed before air transport of patients and if necessary departure delayed. Oxygen ought to be added to inspired air with appropriate supervision in all acutely ill patients. Indications for endotracheal intubation before flight should be generously defined. Continuous pulse oximetry is noninvasive and highly informative. It is urgently recommended that air ambulances be equipped with them. PMID- 2914555 TI - [Dietetic principles after gastrectomy]. PMID- 2914557 TI - [Preparation of angiography catheters for reuse]. PMID- 2914556 TI - [IgE-bearing dendritic cells of the skin. An indication of the pathophysiological importance of Langerhans cells in atopic eczema]. PMID- 2914558 TI - [Cerebral complications in chronic acetylsalicylic acid poisoning]. AB - A 60-year-old woman who for many years had been taking salicylate-containing tablets for headaches, was admitted to hospital, in a somnolent state, because of increasing weakness, tiredness, memory and speech disorders, and tinnitus. Laboratory tests revealed a decompensated metabolic acidosis (pH 7.25), renal insufficiency (creatinine 2.3 mg/dl) and a decreased Quick value (63%). Whole blood acetylsalicylic acid concentration was markedly elevated to 330 micrograms/ml. After treatment of the acidosis with bicarbonate and forced diuresis she at first regained consciousness, but clouding of consciousness again occurred eight hours later progressing to coma with unequal pupils and seizure potentials in the electroencephalogram. Status epilepticus without motor component was diagnosed, perhaps the result of a dysequilibrium of acid-base balance between blood and cerebrospinal fluid. The signs and symptoms were quickly reversed under treatment with clonazepam. PMID- 2914560 TI - [What will become of the calculus detritus?]. PMID- 2914559 TI - [Atrial myxoma and signs of autoimmune disease]. AB - Raised erythrocyte sedimentation rate, mild proteinuria, erythrocyturia and slightly impaired renal function were revealed in a 45-year-old patient complaining of general physical fatigue, fever and pain in the right flank. Interstitial nephritis was confirmed by biopsy. Therefore, an autoimmune disease with renal involvement was diagnosed. Three years later a myxoma of the left atrium was found. After surgical removal of the myxoma the signs of the systemic disease receded and disappeared unexpectedly. At follow-up after 10 years the patient was completely free of symptoms. It is concluded that the signs of the autoimmune disease had been caused by the myxoma. PMID- 2914561 TI - On the release of asbestos fibers from weathered and corroded asbestos cement products. AB - The controversy on whether weathered and corroded asbestos cement products are emitting biologically significant asbestos fiber concentrations in ambient air has not been resolved. Nor is it known if the weathered and corroded asbestos cement products release asbestos fibers which have the same carcinogenic potency as "standard" chrysotile. The purpose of this research project was to develop a method for sampling and measuring asbestos fiber emissions from solid planar surfaces (i.e., roofs and facades) consisting of asbestos cement products and to develop methods for studying the physical and chemical changes and the carcinogenic potency of the emitted fibers. Using this method asbestos fiber emissions in ambient air have been measured in the FRG during 1984/1986. The emissions of asbestos fibers longer than 5 microns were in the range 10(6) to 10(8) fibers/m2.hr. The ambient air concentrations of these asbestos fibers were for the most part less than 10(3) fibers/m3. It was shown that the emitted asbestos fibers were chemically changed and it was shown with animal experiments that their carcinogenic potency did not differ from the carcinogenicity of "standard" chrysotile fibers. PMID- 2914562 TI - A generalized model for the prediction of lead body burdens. AB - A compartmental model of a typical 70-kg male for lead intake, distribution, and transport has been developed based on previous pharmacokinetic models and experimental results for lead in the human body. A set of first-order, linear ordinary differential equations with constant coefficients is solved to predict lead levels in blood, bone, and other compartments as a function of time resulting from inputs from air and/or ingestion. The model has been shown to be in excellent agreement with the measurements of blood lead for a controlled study by M. B. Rabinowitz et al. (1976, J. Clin. Invest., 58, 260-270). Favorable agreement was also found with blood and urine results reported by T. B. Griffin et al. (1975, "Lead," pp. 221-240) providing that an allowance was made for an unmeasured input of lead, originating from smoking, snacks, etc. The predictions of the newly formulated model are compared with those of the established Bernard model (S. F. Bernard, 1977, Health Phys., 32, 44-46). Predictions of blood lead concentration for short periods (on the order of months) are fitted better by the new model, while both models predict similar behavior over the longer term (on the order of 5 years and greater). PMID- 2914563 TI - Age dependence of metals in hair in a selected U.S. population. AB - Concentrations of 28 metals were determined in hair samples from 199 children (age less than or equal to 12 years) and 322 adults (age 13-73) years. Levels of calcium, barium, magnesium zinc, and strontium all show a similar age-dependent increase up to about 12-14 years; levels of aluminum show a decrease with age. Relationships of elemental concentrations with age were examined by using correlation, linear regression, t tests, and discriminant analysis. Statistically significant differences in mean concentration values between children and adults were shown for these metals. Discriminant analysis gave about 95% accuracy in classifying a test data set into the categories of children and adults. A hypothesis suggested by the data is that there is an age-dependent excretion in hair of alkali metals during skeletal growth and development. The observed decrease in aluminum is largely unexplained at this time. PMID- 2914564 TI - Lung cancer in relation to residence in census tracts with toxic-waste disposal sites: a case-control study in Niagara County, New York. AB - Nine selected census tracts containing 12 toxic-waste disposal sites with known or suspected lung carcinogens were identified in Niagara County, New York. Analysis of death certificates of 339 lung cancer cases (decedents) and 676 controls who died of other causes excluding respiratory diseases in 1978-1981 showed no association between death from lung cancer and residence in the selected census tracts (odds ratio = 0.95; 95% confidence interval = 0.65-1.38). Analysis of mail questionnaires from surrogate respondents for 209 lung cancer decedents and 417 controls showed no significant association between lung cancer and a history of ever having resided in the selected census tracts (age-adjusted odds ratio = 1.17; 95% CI = 0.78-1.76) and no significant interaction between such residence and cigarette smoking. Duration of residence in the selected census tracts did not differ between cases and controls. The limitations of this low-cost study design, in terms of response rates and potential misclassification of exposure, were discussed along with its value in interim studies of potentially hazardous dumpsites (prior to more intensive case-control or other studies using better exposure data). PMID- 2914565 TI - Evaluation of the pleural malignant mesothelioma patients with the relation of asbestos exposure. AB - There has been a recent increase in the number of patients with malignant mesothelioma in parts of Japan where Naval shipyards were located during World War II. This can be attributed to asbestos exposure during work in the shipyard. We have studied eight patients who were seen between 1984 and 1986 in Kure Kyosai Hospital. All had a history of asbestos exposure, seven in a Naval shipyard. In these seven cases, the latent period between exposure and the appearance of mesothelioma was 43-49 years. Quantification of asbestos bodies in the lung indicated a high concentration in all patients, giving further weight to the concept that asbestos is an etiologic factor in the genesis of mesothelioma. The major types of asbestos fibers were crocidolite and amosite. The study of structural features of these two types may provide a clue to the pathogenesis of the disease. PMID- 2914566 TI - Effects of ingested crude and dispersed crude oil on thermoregulation in ducks (Anas platyrhynchos). AB - Thermoregulatory effects of ingested doses of Statfjord A crude oil and of this oil mixed with the dispersant Finasol OSR-5 were studied in adult domestic ducks (Anas platyrhynchos) exposed to ambient temperatures of +16 degrees C and -17 degrees C. The data show that ingestion of both the crude and the oil-dispersant mixture resulted in an increased body temperature during exposure to the low ambient temperature (-17 degrees C). Neither contaminant had any effect on body temperature during exposure to +16 degrees C. Ingestion of the contaminants had no effect on metabolic heat production at either ambient temperature. The breast skin temperature of the ducks in both contaminated groups was significantly decreased when the ducks were exposed to the low ambient temperature. This indicates that the increase in body temperature observed in the contaminated ducks at the low ambient temperature is due to an increase in peripheral vasoconstriction. PMID- 2914567 TI - Response of the rat lung to respirable fractions of composite fiber-epoxy dusts. AB - It is unknown whether respirable dusts derived from the machining of composite fiber-epoxy materials pose a health risk. To evaluate the potential pulmonary toxicity of these materials, we studied the effects of six samples of dusts previously well characterized physically, chemically, and morphologically in the lungs of specific pathogen-free rats. A single intratracheal bolus of 5 mg of each sample was injected into separate groups of five rats each. For comparison, free crystalline silica (quartz) and aluminum oxide were used as positive and negative controls in additional animals. One month later, the lungs were fixed and sectioned for light microscopy. Histopathology scores for the six composite epoxy samples showed a continuum of lung injury that was between the negative and positive controls. None of the composite dusts had effects that paralleled those of quartz; however, four of the composite dusts produced reactions that were more severe than that seen with aluminum oxide. Therefore, respirable fractions of some types of composite materials can induce pathological changes in lungs of experimental animals. The features responsible for the variation in host response between samples are, as yet, unclear. PMID- 2914568 TI - Effects of short- and long-term exposure to ozone on heart rate and blood pressure of emphysematous rats. AB - Electrocardiogram and arterial blood pressure of elastase-treated emphysematous rats (E rats) and saline-treated control rats (S rats) were recorded continuously during exposure to either 1 ppm ozone (O3) for 3 hr or 0.5 ppm O3 for 6 hr. The heart rates (HRs) of both groups decreased to about 50 and 65% of the initial levels at the end of 1 ppm and 0.5 ppm O3 exposure, respectively. Mean arterial blood pressures (MAPs) also decreased to about 76 and 82%, respectively. There was no significant difference in these responses between E and S rats, although the levels of HRs and MAPs of the E rats were always a little lower than those of the S rats. Another group of E and S rats was continuously exposed to 0.2 ppm O3 for 4 weeks. The HRs of both E and S groups decreased to about 81 and 88% of the initial levels on the first day, respectively, although they recovered completely by the third day. No significant difference in the variation of HRs during exposure was noted between E and S rats. However, the HR responses of these rats to a challenge exposure of 0.8 ppm O3 for 1.5 hr appeared to be different. That is, S rats were more tolerant of the challenge exposure to O3 for 1.5 hr than the E rats. PMID- 2914569 TI - Potentiation of the expression of nitrogen dioxide-induced lung injury by postexposure exercise. AB - Previous investigations have indicated that postexposure exercise (E) can can potentiate nitrogen dioxide (NO2)-induced lung injury. In this report, we (1) further characterize the potentiation of expression of NO2-induced lung injury in the rat by E; (2) characterize the postexposure period during which such potentiation by E can occur, i.e., "window of susceptibility"; (3) assess whether two E bouts performed during the "window of susceptibility" have even greater potentiating effects; and (4) determine if early postexposure E can extend the window of susceptibility. Groups of Fischer-344 rats were exposed to 100 ppm NO2 for 15 min, exercised at times ranging from 30 min to 24 hr thereafter, and sacrificed during a 24-hr postexposure period. Other exposed rats were exercised 30 min to 24 hr thereafter and sacrificed for lung studies 30 min following the E runs. Still other exposed animals were exercised immediately and at 8 or 24 hr postexposure and sacrificed 30 min after the last E run. NO2-exposed but rested rats, and sham-air-exposed and rested or exercised rats served as controls. E immediately or at 8 hr post-NO2 exposure caused marked increases in lung wet weight (LWW) and right cranial lobe dry weights (RCLDW) and more pronounced histopathologic disturbances beyond those following NO2 exposure and rest only. Potentiation of injury was not observed in rats exercised 24 hr after exposure. The pattern of subsidence of the LWW and RCLDW increases after immediate or 8 hr E differed with the increases in the former being more persistent. Two E bouts (30 min and 8 hr postexposure) caused lung changes consistent with an additive effect. E performed immediately after NO2 exposure extended the window of susceptibility to E beyond 24 hr. PMID- 2914570 TI - Another perspective and some immoderate proprosals on "teacher empowerment". PMID- 2914571 TI - Survey on prerefferal practices: responses from State deparetments of education. AB - A six-item survey was sent to state directors of special education (or their equivalent) in all 50 states and the District of Columbia. Items were developed to assess the type and level of prereferral intervention usage reported by state level special education administrators. Despite a lack of empirical support and a relatively inconclusive success rate, many state level administrators reported that they require or recommended the use of prereferral intervention strategies. PMID- 2914572 TI - Effects of examiner familiarity on Black, Caucasian, and Hispanic children: a meta-analysis. AB - This article presents a quantitative synthesis of examiner familiarity effects on Caucasian and minority students' test performance. Fourteen controlled studies were coded in terms of methodological quality (high vs. low) and race-ethnicity (Caucasian vs. Black and Hispanic). An analogue to analysis of variance conducted on weighted unbiased effect sizes indicated that examiner familiarity produced a significant effect, with Caucasian and minority examinees' test performance raised by .05 and .72 standard deviations, respectively. Examiner familiarity's differential effect on Caucasian and minority examinees did not interact with the methodological quality of the studies. Nevertheless, limitations of the extant data base require caution in drawing implications for assessment practice. PMID- 2914573 TI - Community involvement of persons with severe retardation living in community residences. AB - A national survey was conducted with 294 community residential facilities (CRFs) serving adults with severe retardation. Respondents were asked to rate 38 community-based activities twice: one rating representing the activity involvement of the residents living in the CRFs, and one rating representing the perceived activity involvement of "average," well-integrated community members. Nonhandicapped community members were perceived to have significantly more involvement in 30 activities than adults living in CRFs. Group home and foster home residents were perceived to be more involved in employment or day activities outside the residence, use of health care services, walking or wheelchair strolling for pleasure, and use of parks or zoos than nonhandicapped community members. PMID- 2914574 TI - Effects of a taped-words treatment on reading proficiency. AB - In an effort to increase reading proficiency, five 9th- and 10th-grade students with behavior disorders were instructed to read along with an audio type of vocabulary words recorded at 80 words per minute. Effects of the taped-words intervention on rate of reading vocabulary words as well as generalization effects of reading passages containing some of the same vocabulary words were assessed within a multiple baseline design. Results suggested significant effects due to practice. Minimal generalization from reading word lists to reading passages was demonstrated. The results of the present study are compared with similar investigations. PMID- 2914576 TI - Is AIDS a biasing factor in teacher judgment? AB - This study examined the effect that knowledge of a student having AIDS (Acquired Immune Deficiency Syndrome) would have on regular-education teacher judgment regarding special education placement. Regular-education, third-grade teachers in Indiana were sent one of two psychological reports. The reports were identical except that one report stated that the student had AIDS and the other stated that the student had rheumatic fever. AIDS was not found to be a biasing factor in teachers' judgments regarding special education services. PMID- 2914575 TI - Mathematics achievement of hearing impaired adolescents in different placements. AB - This study, involving 215 students and 63 teachers, addressed three concerns related to mainstreaming for hearing imparied students: the selection process, the difference between a mainstream placement with an interpreter and a self contained placement, and the quality of the educational experience. Almost half of the variance in achievement between the two settings is described. Three conclusions can be drawn. First, student background factors are a primary determinant of achievement. Second, mainstreaming with an interpreter has no specific effect on achievement for hearing impaired students. Third, the quality of instruction is the prime determinant of achievement, regardless of placement. PMID- 2914577 TI - Production and utilization of extracellular matrix components by human melanocytes. AB - Normal human melanocytes were separated from keratinocytes and maintained in culture using KGM medium supplemented with 12-O-tetradecanoylphorbol acetate and cholera toxin. The melanocytes were examined for the production of extracellular matrix molecules including fibronectin, laminin, and thrombospondin and for the utilization of these molecules in adhesion and motility assays. Melanocytes produced significant amounts of fibronectin as indicated by biosynthetic labeling/immunoprecipitation and by enzyme-linked immunosorbent assay (ELISA). Fibronectin was expressed on the surface of these cells. Laminin was also produced by melanocytes and expressed on the cell surface. The amount of laminin produced was significantly less than the amount of fibronectin. In contrast, melanocytes did not produce measurable thrombospondin as indicated by biosynthetic labeling/immunoprecipitation. Only traces of thrombospondin were detected by ELISA and no surface fluorescence was observed. When examined in adhesion and motility assays, melanocytes were found to utilize fibronectin for both processes. Laminin also stimulated adhesion but it was much less effective than fibronectin. Thrombospondin did not stimulate either attachment and spreading or motility. The pattern of extracellular matrix molecule production and utilization by melanocytes is significantly different from that shown previously for human epidermal keratinocytes (J. Varani et al., 1988, J. Clin. Invest. 81, 1537). These differences may underlie the differences with which the two cell types interact with basement membranes in vivo. PMID- 2914578 TI - Myogenic cells of regenerating adult chicken muscle can fuse into myotubes after a single cell division in vivo. AB - Autoradiographic studies were carried out on regenerating muscles of adult chickens. Three different muscles of hens were injured, and tritiated thymidine (1 microCi/g) was injected at various times after injury to label replicating muscle precursors. Detailed comparisons of grain counts over premitotic nuclei in samples removed one hour after injection of tritiated thymidine, and of postmitotic myotube nuclei in samples removed 10 days after injury (when labeled precursors had fused to form myotubes), revealed how many times some labeled precursors had divided before fusing into myotubes. DNA synthesis in muscle precursors was initiated 30 h after injury. Grain counts of myotube nuclei indicated that many muscle precursors labeled at the onset of myogenic cell proliferation had divided only once, or twice, before fusing into myotubes. The relationship of these in vivo results to the cell lineage model of myogenesis is discussed. PMID- 2914579 TI - Synthesis of shock proteins in cultured fetal mouse myocardial cells. AB - We examined the synthesis of shock proteins in cultured fetal mouse myocytes. The preparation is free from fibroblasts, and the cells are vital and morphologically intact with respect to beat frequency and electron microscopy. Cultured myocytes from fetal mouse heart respond to heat shock and cadmium chloride, H2O2, allylamine, cyclosporine, and azathioprine exposure with the synthesis of shock proteins. Heat shock induces the de novo synthesis of two proteins of 71 and 68 kDa; cadmium chloride induces, in addition, a protein of 30 kDa. The other substances tested provoke the synthesis only of the 30-kDa polypeptide. The formation of heat shock proteins is concentration-dependent: Cyclosporine provokes the de novo synthesis of the 30-kDa polypeptide at concentrations above 10 ng/ml, whereas azathioprine causes the same effect at concentrations above 50 micrograms/ml. Hence cyclosporine might be cardiotoxic already at concentrations below the pharmacological dosages while azathioprine influences the myocytes only at concentrations much higher than the therapeutic level. Our results indicate that heat shock protein expression in cultured myocytes may be a useful tool to monitor cardiotoxicity. PMID- 2914580 TI - The protein composition of the nuclear matrix of murine P19 embryonal carcinoma cells is differentiation-stage dependent. AB - The protein composition of the nuclear matrix of murine P19 embryonal carcinoma (EC) cells was compared with that of clonal derivatives of P19 EC differentiated in vitro, and with that of P19 EC cells induced to differentiate with retinoic acid (RA). Several major differences in nuclear matrix protein composition were found between the cell lines tested. Some polypeptides were found to occur only in EC cells, whereas others proved to be restricted to one or more of the differentiated derivatives. During RA treatment of EC cells a transient expression of some matrix proteins was observed. Several new proteins appeared, and others disappeared. Our data indicate that the protein composition of the nuclear matrix is a sensitive gauge for the differentiation state of cells. PMID- 2914581 TI - Platelet-derived growth factor is not chemotactic for human peripheral blood monocytes. AB - PDGF is a mitogenic protein stored in platelets and released upon platelet degranulation. Recent evidence indicates that PDGF plays an important role in both physiologic and pathophysiologic processes, particularly in tumorigenesis, wound healing, pulmonary fibrosis, and atherogenesis. In addition to its mitogenic potential, it has been reported that PDGF stimulates monocyte chemotaxis. Since the recruitment of monocytes from the peripheral vasculature is an important event in vivo, the potential role of PDGF as a monocyte chemoattractant has significant biologic implications. However, we now report that homogeneous human PDGF from platelets and a recombinant PDGF-2 homodimer do not stimulate monocyte chemotaxis. In contrast to previous reports these results indicate that PDGF is not a monocyte chemoattractant. PMID- 2914582 TI - Lateral diffusion of lectin receptors in fibroblast membranes as a function of cell shape. AB - Anchorage-dependent fibroblasts respond to biochemical growth signals only when attached to and spread on a suitable substrate surface. Attachment of fibroblasts initiates a cytoskeletal assembly process that results in the organization of long actin stress fibers and microtubules which may be required for transmembrane signal transduction. Fibroblasts maintained in suspension, however, remain spherical with no apparent stress fibers or lengthy microtubules. Because of the significant differences in cytoskeletal organisation induced by shape modification, and the resulting possible changes in organization and dynamics of membrane receptors, the technique of fluorescence redistribution after photobleaching (FRAP) was employed to examine the lateral mobility of wheat germ agglutinin (WGA) and succinylated concanavalin A (sCon A) receptors in the plasma membrane of untransformed and Kirsten murine sarcoma virus-transformed Balb/c 3T3 fibroblasts in the spread and spherical state. An examination of FITC-WGA and FITC-sCon A binding to the plasma membrane for both cell lines in a spread or spherical state demonstrated no significant differences in the number of WGA or Con A receptors as a function of shape or transformation. The primary observations from this study are (a) membrane WGA and sCon A receptors in spherical Balb/c 3T3 fibroblasts display mobility 12 times faster than in the spread state, while phospholipid mobility is similar and apparently shape independent, (b) transformed cells in the spread state have WGA and sCon A receptor mobilities similar to those of untransformed cells in the spread state, (c) flat adherent, but not unattached spherical, Balb/c 3T3 fibroblasts are subject to Con A-induced global modulation and (d) transformed cells in the spherical state contain a significant population of cells (approximately 30%) with WGA receptor mobilities faster than those observed in spherical untransformed cells. These observations are discussed in terms of a linked matrix model for membrane protein diffusion. PMID- 2914583 TI - Clonal selection by fluorescence redistribution after photobleaching (FRAP)--a "fast" lateral mobility fibroblast mutant (E7G1). AB - Fluorescence redistribution after photobleaching (FRAP) was utilized to select a "fast" lateral mobility clone from Kirsten murine sarcoma virus-transformed 3T3 (KMSV-3T3) fibroblasts. The clone, E7G1, demonstrated a lateral mobility for membrane wheat germ agglutinin (WGA) and succinylated concanavalin A (sCon A) receptors of (2.1 +/- 1.6) X 10(-9) cm2/s and (2.7 +/- 2.3) X 10(-9) cm2/s, respectively. These mobilities were approximately equivalent to phospholipid mobility (2.8 +/- 1.9 X 10(-9) cm2/s). The fast mobility phenotype is observed when the cells are unattached and spherical. Upon attachment, the mobility decreases to (0.19 +/- 0.19) X 10(-9) cm2/s. In addition, the ability of Con A to initiate global modulation was completely lost in spread as well as spherical cells in the E7G1 fast mobility clone. A comparison of F-actin patterns between untransformed Balb/c fibroblasts and the E7G1-transformed line suggests a correlation between well-developed stress fiber assemblies and the ability to induce global modulation. The fast mobility clone was stable for at least 23 passages. PMID- 2914584 TI - Translational regulation of the differential synthesis of nonmuscle tropomyosin isoforms. AB - Regulation of the differential synthesis of tropomyosin (TM) isoforms in chicken embryo fibroblasts was studied. Cell-free translation experiments with total RNA and Northern blot analyses of TM mRNAs from fractionated polysomes were performed. Unlike the major isoforms, mRNAs encoding at least one of the minor isoforms were only partially associated with the heavy polysomes. Thus, these experiments revealed that translational regulation plays a role in controlling the relative amounts of major and minor isoforms in the cell. PMID- 2914585 TI - HMG proteins released from the chromatin following incubation of mammalian nuclei with ethidium bromide. AB - The low-molecular-mass high-mobility group (HMG) chromosomal proteins, namely HMG 14, HMG-17, and HMG-I, which have been found in several proliferating tissues, are released following incubation of nuclei isolated from young rat thymus and from human placenta in a low ionic strength medium containing the intercalating agent ethidium bromide. The amount of HMG proteins released is drug concentration dependent, but at very high concentrations (20-40 mM) other low- and high molecular-mass proteins, and even histones, are released. These results suggest a very weak interaction of the HMG proteins with DNA, so that they can be easily detached from the chromatin as a consequence of the interaction of DNA with the intercalating agent. PMID- 2914586 TI - No significant overreplication occurs in Ehrlich ascites cells during and after reversal of hypoxia. AB - Labeling with bromodeoxyuridine and analysis by isopycnic banding for emergence of DNA-helices density-labeled in both strands (HH-DNA) were used to examine whether transient controlled hypoxia induces significant overreplication in the DNA of cultured Ehrlich ascites cells within a single cell cycle. Diverse situations of the hypoxic period (4-8 h) within the BrdUrd labeling time (8-16 h) were tested. If transversal of more than one complete cell cycle by very fast cycling individual cells was avoided by using short BrdUrd labeling periods or by addition of colcemid, HH-DNA was never detected. This indicates that hypoxia does not induce significant overreplication under the conditions chosen and, in particular, that the burst of replicon initiations occurring after reoxygenation of hypoxic cells principally is not due to overreplication. PMID- 2914587 TI - Quiescent human peripheral blood lymphocytes do not contain a sizable amount of preexistent DNA single-strand breaks. AB - Sedimentation of nucleoids through neutral sucrose density gradients has shown that nucleoids isolated from phytohemagglutinin (PHA)-stimulated human peripheral blood lymphocytes (PBL) sediment faster than nucleoids derived from quiescent lymphocytes, which was attributed to rejoining of DNA single-strand breaks (SSB) present in the resting cells (A.P. Johnstone, and G.T. Williams (1982) Nature (London) 300, 368). We isolated PBL from donors and determined the amount of SSB in nonradiolabeled, untreated resting and PHA-stimulated cells by applying the alkaline filter elution technique. Calibration was based on dose-dependent induction of SSB by 60Co-gamma-radiation. Quiescent cells did not contain a sizable amount of SSB. Mitogen-stimulated cells showed equally low amounts of SSB per cell. The present study indicates that the interpretation of the results obtained with the nucleoid sedimentation technique concerning the supposed rejoining of SSB in PHA-stimulated human lymphocytes is incorrect. Other, equally sensitive, techniques such as alkaline filter elution appear to be preferable for studies on DNA damage and repair. PMID- 2914588 TI - Myasthenia gravis and chronic lymphocytic leukaemia. PMID- 2914589 TI - Successful treatment of hemorrhagic syndrome due to an acquired, combined deficiency of factors VII and X in a patient with multiple myeloma and amyloidosis. PMID- 2914590 TI - Hypersensitivity reactions to heparin and the use of new low molecular weight heparins. PMID- 2914591 TI - Fatal paralytic ileus following vindesine chemotherapy in a patient with myeloma associated amyloidosis. PMID- 2914592 TI - Resistant multiple myeloma treated with mitozantrone in combination with vincristine and dexamethasone (MOD) PMID- 2914593 TI - Molecular analysis of the bcr rearrangement in a case of Ph'-negative blastic crisis of Ph'-positive chronic myelogenous leukemia. AB - We describe here a patient with Ph'-positive chronic myelogenous leukemia (CML) who developed a Ph'-negative blastic crisis. The blast DNA was analyzed on two different occasions, at the beginning of the blastic phase and at the end, shortly before the patient's death. Although cells from both samples had no Ph' chromosome marker (not even a masked one) we could detect a rearrangement of the bcr gene in the second DNA sample, using a '3'-bcr' probe. The same probe and a '5'-bcr' probe failed to detect any rearranged band in the first DNA sample. No rearrangement was identified at the c-myc and N-ras loci, while a slight c-myc amplification was evident in both DNA samples tested. PMID- 2914594 TI - Immunological recovery and dose evaluation in IFN-alpha treatment of hairy cell leukemia: analysis of leukocyte differentiation antigens, NK and 2',5' oligoadenylate synthetase activity. AB - A low-dose interferon (IFN)-alpha regimen for the treatment of hairy cell leukemia (HCL) was evaluated by following changes in leukocyte differentiation antigens (LDA), natural killer cell (NK) and 2',5'-oligoadenylate (2-5A) synthetase activities. Due to hairy cells' (HC) weak expression of several antigens positive for T cells, B cells, NK cells and monocytes, the use of a double marker specific for hairy cells was needed to distinguish the different subpopulations. Analysis of LDA in peripheral blood (PB) showed a total normalization of the T cell and monocyte numbers within 90 days, the number of NK cells normalized in 90 to 180 d, whereas normalization of B cell number was seen only after 180 to 360 d of treatment. Mean pretreatment 2-5A synthetase activity was normal or low, but upon treatment the levels rose immediately to higher than normal values and remained high throughout the study. Pretreatment NK activity was low, but normalized after between 90 to 360 d, except in 2 patients with severe splenomegaly. In vitro incubation of peripheral blood mononuclear cells (PBMNC) with IFN-alpha induced activation of the NK and 2-5A synthetase activity in untreated patients, but with treatment these effects were gradually abolished, indicating an increasing effect of IFN-alpha in vivo with time. These results shows that the different PBMNC subpopulations and important immunological functions normalize with treatment. This normalization is, however, not seen until at least after 1 year of treatment, indicating that the treatment schedule should be longer. As no exhaustion to the effect of IFN was seen, as measured by the 2-5A synthetase activity, a continuing beneficial effect of treatment is anticipated. The increasing effect of IFN-alpha after the first signs of clinical effect suggests that the doses used in the present study were higher than necessary. PMID- 2914595 TI - Haem arginate treatment for hereditary sideroblastic anaemia. AB - It has been shown that haem arginate treatment increases blood cell counts, improves the sideroblast status of the bone marrow and normalises decreased activities of haem synthesising enzymes in some patients with acquired sideroblastic anaemia, or with other types of myelodysplastic syndromes. 4 patients with hereditary sideroblastic anaemia (HSA), belonging to two families, were therefore treated with haem arginate infusions, 3 mg/kg, on 4 consecutive days, and thereafter weekly for 10 wk. No effect was observed on the mildly anaemic haemoglobin levels or on the red cell counts. However, the initially low or low-normal myeloid to erythroid ratio in the marrow increased in all patients. A consistent decrease in the percentage of ring sideroblasts and other abnormal sideroblasts was seen in 1 patient (Family A), and a temporary decrease of abnormal sideroblasts took place during the most intensive treatment period in 2 other patients (Family B). Two of three initially abnormal haem synthesising enzyme activities became normal in Family A, whereas no clearly consistent effects on the haem synthesising enzymes were observed in Family B. The present study shows that haem arginate infusions can normalise the activities of haem synthesising enzymes in some patients with HSA. Further studies are needed to evaluate the impact of haem infusions on the iron balance of these patients. PMID- 2914596 TI - Trends in the incidence of multiple myeloma in Denmark 1943-1982: a study of 5500 patients. AB - The incidence of multiple myeloma in Denmark during the period 1943-82 was examined, based on the files of the Danish National Cancer Registry. A total of 5535 patients (3023 male and 2512 female) were registered. Over the period 1943 62 the incidence increased 2- to 3-fold for both men and women, but the increase in men was steeper and was seen several years before the increase in women in all 5-yr age groups from 50 to 75 yr of age. This pattern would be compatible with an impact of environmental factors. The increase, also percentagewise, rose with increasing age. Since 1963 the incidence has been virtually stable with a possibly decreasing trend during the latest 5- to 10-yr period. PMID- 2914597 TI - Childhood transient erythroblastopenia complicated by thrombocytopenia and neutropenia. AB - We report on 4 children with transient erythroblastopenia complicated by thrombocytopenia and/or neutropenia. Bone marrow examination revealed severe erythroid hypoplasia with normal granulopoiesis and thrombopoiesis. Human parvovirus B19 infection was confirmed serologically in 2 children. An in vitro study using autologous bone marrow cells after recovery demonstrated IgG-mediated inhibition of erythropoiesis in 4 children. Additionally, antibodies directed against platelets and neutrophils were detected. These findings suggest that the IgG-mediated mechanism may be pathogenetic for the transient pancytopenia of these children. PMID- 2914598 TI - Cultured human basophils with ultrastructural and ultracytochemical features of mast cells. AB - To clarify whether in vitro-cultured basophils have features of mast cells, basophils grown in semisolid and liquid culture were studied ultrastructurally and cytochemically and were compared with freshly isolated basophils and mast cells. Ultrastructurally, the cultured basophils had pleomorphic cytoplasmic granules, some of which were similar to mast cell granules. However, scroll formation, characteristic of mast cell granules, was not observed in cells grown in semisolid and liquid culture. Cytochemically, the reactivity patterns of acidic glycoconjugates in the cultured cells more closely resembled those of the freshly isolated basophils than of the mast cells. In addition, the basophils grown in liquid culture showed a more matured form and had stronger reactivity to glycoconjugates, acid phosphatase and peroxidase than did the cells grown in semisolid culture, suggesting that the liquid culture system was better for the basophil. PMID- 2914599 TI - Clinical manifestations and laboratory findings in patients with lupus anticoagulants. AB - Clinical and laboratory features were evaluated in 48 patients with lupus anticoagulants and the efficiency of three different assays in the detection of lupus anticoagulants was compared. The diagnosis of lupus anticoagulants was based on a prolonged activated partial thromboplastin test not corrected in a mixture of 1:1 with normal plasma and lack of specific inhibitors against coagulation factors. Platelet neutralization procedure was positive for lupus anticoagulants in 98% of the patients, tissue thromboplastin inhibition ratio in 79%, and kaolin clotting time index in 77%. At least one of the assays was positive in 100% of the cases. The largest minority of the patients (31%) suffered from systemic lupus erythematosus. The others had a variety of non immunological disorders. In the 13 patients who had been operated on, only 1 with renal failure developed hemorrhagic complications after renal biopsy due to thrombocytopathy. The incidence of recurrent spontaneous miscarriage, immune thrombocytopenia and positive direct antiglobulin test, anti-nuclear and anti-DNA antibodies and VDRL was significantly higher in patients with lupus anticoagulants and systemic lupus erythematosus compared to patients with lupus anticoagulants but without systemic lupus erythematosus. PMID- 2914600 TI - Development of polycythaemia vera in a patient with myelofibrosis. AB - In March 1981, a 53-year-old man presented with itching and was diagnosed as having myelofibrosis. There was gradual enlargement of the spleen over the following 5 yr. His spleen had to be removed in February 1986 because of physical discomfort. 3 months post-splenectomy he became polycythaemic. Bone marrow examination was consistent with severe myelofibrosis. It was possible to demonstrate erythropoietin-independent BFU-E from peripheral blood, and ferrokinetic studies showed that erythropoiesis was localised to the liver with little bone marrow activity. Thus, despite severe marrow fibrosis, liver erythropoiesis was now polycythaemic, suggesting the coexistence of myelofibrosis and polycythaemia vera. PMID- 2914601 TI - A myelokathexis-like variant of myelodysplasia. AB - A 34-year-old woman presented with pancytopenia, profound neutropenia and repeated infections. A bone marrow specimen revealed hypercellularity with trilineage dysplasia and bizarre granulocytic morphology identical to that of the rarely reported myelokathexis. Investigations revealed defects in platelet and neutrophil functions and markedly reduced colony-to-cluster ratio in bone marrow culture. She required treatment with antibiotics, surgical intervention for a gangrenous abdominal wall, and eventually underwent a successful allogeneic bone marrow transplant from her sister. This case suggests that myelokathexis is an unusual form of myelodysplasia with a relatively benign course and presenting at a young age. PMID- 2914602 TI - A unique signature identifies a family of zinc-dependent metallopeptidases. AB - The primary sequence motif HExxH has been found in many zinc-dependent endopeptidases. We show that a larger signature comprising this sequence is common to most of the known zinc-dependent endopeptidases, and that the presence of the signature can be indicative of membership in the family. A search of the protein sequence databases for entries containing the signature retrieved several unexpected potential zinc endopeptidases. PMID- 2914603 TI - 87Rb NMR studies of the perfused rat heart. AB - We have studied 87Rb+ fluxes in the perfused rat heart using nuclear magnetic resonance spectroscopy (NMR). A simple model for the interpretation of the data is presented. A comparison of radioactively measured K+ fluxes and the K+ fluxes deduced from the 87Rb+ measurements shows them to be very similar. This method provides a means of noninvasively measuring uni-directional K+ fluxes in the heart. PMID- 2914604 TI - Improved strategies for the determination of protein structures from NMR data: the solution structure of acyl carrier protein. AB - The hybrid method that combines the early stages of a distance geometry program with simulated annealing in the presence of NMR constraints was optimized to obtain structures fully consistent with the observed NMR data. This was achieved by using more restrictive bounds of the NOE constraints than those usually used in the literature and by grouping the NOEs into classes dependent on the quality of the experimental NOE data. The 'floating' stereospecific assignment introduced at the simulated annealing stage of the calculations further improved the definition of the local conformation. An improved sampling and convergence property of the hybrid method was obtained by means of fitting the substructure obtained from the distance geometry program to different conformations. Compared to the standard hybrid methods, this procedure gave superior structures for a 77 amino acid protein, acyl carrier protein from Escherichia coli. PMID- 2914605 TI - One of two subunits of masking protein in latent TGF-beta is a part of pro-TGF beta. AB - A high molecular mass latent form of transforming growth factor type-beta (TGF beta) was purified to homogeneity from rat platelets by a seven-step procedure involving group-specific affinity chromatographies on Red-Toyopearl and zinc chelating-Sepharose. The purified latent TGF-beta was a complex of TGF-beta (25 kDa) and the binding protein previously named masking protein (approximately 400 kDa) [(1986) Biochem. Biophys. Res. Commun. 141, 176-184]. Analysis of the peptide structure by gel electrophoresis showed that the masking protein consisted of two subunits of 39 kDa and 105-120 kDa linked by disulfide bonds. N terminal amino-acid sequencing of the 39 kDa subunit indicated that this subunit was identical to the N-terminal part of the TGF-beta precursor. PMID- 2914606 TI - The tetanus toxin light chain inhibits exocytosis. AB - The intracellular action on exocytosis of various forms of tetanus toxin was studied using adrenal medullary chromaffin cells, the membrane barrier of which has been removed by permeabilization with streptolysin O. Such cells still release catecholamines on stimulation with calcium. The two-chain form of tetanus toxin (67 nmol/l) strongly inhibited exocytosis, but only if dithiothreitol was present as a reducing agent. Purified light chain completely prevented [3H]noradrenaline release with a half-maximal effect at about 5 nmol/l. Heavy chain (up to 11 nmol/l) and unprocessed single-chain toxin (up to 133 nmol/l) were without effect. It is concluded that the original single-chain form of tetanus toxin has to be processed by proteolysis and reduction to yield a light chain which inhibits transmitter release. PMID- 2914607 TI - Calcium regulates the rate of rhodopsin disactivation and the primary amplification step in visual transduction. AB - The kinetics of the light-induced activation of transducin as well as the subsequent disactivation process can be monitored by means of a specific light scattering transient PA. In this communication it is demonstrated that the rate of transducin disactivation is calcium dependent, increasing when the calcium concentration is decreased. As a consequence of the accelerated recovery in low calcium, the time to the peak of the transducin activation process is shortened and the gain of the primary amplification step, i.e. the number of transducin molecules activated per bleached rhodopsin, is reduced. Experiments using hydroxylamine as an artificial quencher of rhodopsin activity suggest that calcium acts upon rhodopsin kinase and not upon the rate of the GTPase. This would indicate that calcium may control visual adaptation not only by regulating guanine cyclase activity, but also by affecting the primary step in the transduction cascade, the rhodopsin-transducin coupling. PMID- 2914608 TI - Ricin A-chain induces fusion of small unilamellar vesicles at neutral pH. AB - The interaction of ricin and its constituent polypeptides, the A- and B-chain, with small unilamellar vesicles of dipalmitoylphosphatidylcholine (DPPC) or dimyristoylphosphatidylcholine (DMPC) was investigated by means of differential scanning calorimetry measurements. The A-chain, at neutral pH, entirely shifted the endothermic peak of small unilamellar vesicles of DPPC from 37 degrees C to 41 degrees C at low protein/lipid ratios. The potency of either ricin or the B chain to induce the shift of endothermic peak was much less than that of the A chain. The A-chain was also found to cause mixing of endothermic peaks of DMPC vesicles and DPPC vesicles. These data strongly suggest that the A-chain has the ability to induce fusion of phospholipid vesicles. PMID- 2914609 TI - One left-handed strand in DNA-oligonucleotide complexes? AB - A single strand of oligonucleotide can bind to double helical DNA under certain conditions. This must involve some unwinding of the original double helix in a process leading to the formation of a three-stranded region. The free energy for such an entropically unlikely reaction may come from a change in the degree of supercoiling of the original DNA. The conformation of the triple strand is investigated here using computer graphics and molecular mechanics calculations. It is suggested that on binding the oligonucleotide (strand 3) to two paired strands (1 and 2) in a supercoiled DNA molecule, strand 2 might adopt a left handed conformation whilst strand 1 and strand 3 pair in the normal Watson-Crick B-configuration. PMID- 2914610 TI - Selective cleavage of skeletal myosin subfragment-1 to form a 26 kDa peptide which shows ATP-sensitive actin binding. AB - A 26 kDa peptide has been cleaved from the C-terminus of the S1 heavy chain with formic acid. Cleavage occurs in the '50 kDa' domain probably at the Asp-600-Pro 601 bond. This fragment has been renatured in the presence of the A2 light chain and the 26 kDa(A2) complex shown to interact with actin in an ATP-sensitive manner. PMID- 2914611 TI - The refined 2.0 A X-ray crystal structure of the complex formed between bovine beta-trypsin and CMTI-I, a trypsin inhibitor from squash seeds (Cucurbita maxima). Topological similarity of the squash seed inhibitors with the carboxypeptidase A inhibitor from potatoes. AB - The stoichiometric complex formed between bovine beta-trypsin and the Cucurbita maxima trypsin inhibitor I (CMTI-I) was crystallized and its X-ray crystal structure determined using Patterson search techniques. Its structure has been crystallographically refined to a final R value of 0.152 (6.0-2.0 A). CMTI-I is of ellipsoidal shape; it lacks helices or beta-sheets, but consists of turns and connecting short polypeptide stretches. The disulfide pairing is CYS-3I-20I, Cys 10I-22I and Cys-16I-28I. According to the polypeptide fold and disulfide connectivity its structure resembles that of the carboxypeptidase A inhibitor from potatoes. Thirteen of the 29 inhibitor residues are in direct contact with trypsin; most of them are in the primary binding segment Val-2I (P4)-Glu-9I (P4') which contains the reactive site bond Arg-5I-Ile-6I and is in a conformation observed also for other serine proteinase inhibitors. PMID- 2914612 TI - The fast-twitch muscle calsequestrin isoform predominates in rabbit slow-twitch soleus muscle. AB - The major form of calsequestrin in rabbit slow-twitch soleus muscle is shown to be identical to that isolated and cloned from rabbit fast-twitch muscle on the following bases: identity of cDNAs cloned from mRNAs from the two muscle sources; equivalent hybridization of a fast-twitch calsequestrin cDNA probe to mRNAs isolated from fast-twitch and slow-twitch muscles; identity of the 23 amino terminal amino acids; strong binding of 45Ca2+ in a gel overlay of slow muscle sarcoplasmic reticulum protein to a band at the level of the fast-twitch calsequestrin isoform and only weak binding at the level of the cardiac isoform. No evidence was obtained for developmentally regulated alternative splicing of the calsequestrin transcript in mature slow or fast-twitch muscle. PMID- 2914613 TI - Identification of cholera toxin-binding sites in the nucleus of intestinal epithelial cells. AB - Post-embedding immunogold electron microscopy shows several binding sites for cholera toxin in mouse intestinal epithelial cells, particularly in the heterochromatin of the nucleus as well as in the plasma membrane. Anti ganglioside GM1 antibodies also bound to the nucleus, but did not interfere with the binding of toxin. 125I-labelled toxin bound specifically to a nuclear preparation from rabbit intestinal cells. PMID- 2914614 TI - Identification of the cartilage alpha 1(XI) chain in type V collagen from bovine bone. AB - Type V collagen prepared from bovine bone was resolved into three distinct alpha chains by high performance liquid chromatography and gel electrophoresis. Peptide mapping established two chains as alpha 1(V) and alpha 2(V) as expected and the third as the cartilage alpha 1(XI) chain (previously thought to be unique to cartilage). In adult bone, the type V collagen fraction was richer in alpha 1(XI) chains than in fetal bone (about 1/3 of the chains in the adult). How these polypeptides are organized into native molecules is not yet clear, though the stoichiometry suggests cross-type heterotrimers between the type V and XI chains. PMID- 2914615 TI - Cleavages of aromatic ring and beta-O-4 bond of synthetic lignin (DHP) by lignin peroxidase. AB - Lignin peroxidase from a white-rot basidiomycete, Phanerochaete chrysosporium, catalyzed cleavages of the aromatic ring and the beta-O-4 bond of a synthetic lignin, a dehydrogenation copolymer (DHP) of coniferyl alcohol and a (beta-O-4) (beta-beta) lignin substructure model trimer. PMID- 2914616 TI - Depolarization of human neuroblastoma cells as a result of muscarinic receptor induced rise in cytosolic Ca2+. AB - The role of intracellular free Ca2+ in muscarinic-receptor linked depolarization of SH-SY5Y neuroblastoma cells has been determined by using the bisoxonol membrane potential probe DiBaC4-(3) and intracellular Ca2+ indicator fura-2 respectively. Carbachol and the Ca2+ ionophore, ionomycin, at concentrations which caused similar rises in intracellular Ca2+ increased the bisoxonol fluorescence (depolarization) to the same extent. The membrane potential responses, but not the changes in intracellular Ca2+, were dependent on extracellular Na+. Ionomycin depletion of intracellular Ca2+ with EGTA and ionomycin or loading the cells with a Ca2+ buffer, BAPTA, reduced the carbachol induced depolarization. The results suggest that a rise in intracellular Ca2+ may cause depolarization through an increase in the Na+ permeability. PMID- 2914617 TI - XANES spectroscopy sensitivity to small electronic changes. Case of carp azidomethemoglobin. AB - Spin states equilibrium of hemoglobin-iron varies with external conditions: pH, allosteric effectors, temperature. The small electronic reorganization of the iron caused by the spin state changes has been detected by X-ray absorption near edge structure (XANES) spectroscopy at room temperature. The iron K-edge region which is sensitive to spin state is located in 7110-7130 eV. Here are presented the 100% high spin and 100% low spin XANES spectra of carp azido ferric hemoglobin. PMID- 2914618 TI - Short model peptides having a high alpha-helical tendency: design and solution properties. AB - Secondary structure is not typically observed for small peptides in solution. Several of the properties of alpha-helical peptides are known which lead to the stabilization of the structure. The utilization of all the known factors important for alpha-helical stabilization in the design of model alpha-helical peptides (MAP) is reported. The peptides are based on the repeating eleven amino acid sequence, Glu-Leu-Leu-Glu-Lys-Leu-Leu-Glu-Lys-Leu-Lys (MAP1-11). The CD spectra of these peptides give evidence for more alpha-helical content than has been reported for any short peptide (less than 18 amino acids) to date. This alpha-helical tendency does not require the presence of lipid or reduced temperature. For instance, Suc-[Trp9]MAP9-3'' amide (5), a seventeen amino acid peptide has 100% and 80% alpha-helical contents at 1.7 x 10(-4) M and 1.7 x 10( 5) M, respectively. Suc-[Trp9]MAP2-11 amide (3), merely ten amino acids in length, is 51% alpha-helical at 1.7 x 10(-4) M in 0.1 M phosphate buffer at room temperature. In the presence of lipid or trifluoroethanol, the alpha-helical content of these peptides is increased. This series of peptides demonstrates the complimentarity of various secondary structure design principles and the extent to which structure can be induced in small linear peptides. PMID- 2914619 TI - Hormone synthesis in human thyroglobulin: possible cleavage of the polypeptide chain at the tyrosine donor site. AB - At moderate iodination levels (20 iodine atoms/mol) human thyroglobulin (hTg) produces after reduction a hormone-rich peptide of 26 kDa which contains the preferential hormonogenic 'acceptor' tyrosine (Tyr 5) of the protein. The site of cleavage of the hTg chain was demonstrated by analysis of the 26 kDa tryptic hydrolysis products. It consistently yielded the peptide Gln-82-Val-129 which consequently made it possible to localize the hTg chain cleavage at tyrosine residue 130. Evidence for tyrosine involvement in hTg cleavage during thyroid hormone formation supports the hypothesis that peptide bond cleavage would occur at the 'donor' tyrosine residue and suggests that tyrosine 130 would be the donor site reacting with the major hormone-forming acceptor site (Tyr 5) of hTg. PMID- 2914620 TI - Developmental regulation of five subunit specific mRNAs encoding acetylcholine receptor subtypes in rat muscle. AB - The muscular content of the mRNAs encoding the five subunits of the nicotonic acetylcholine receptor was measured during postnatal development in the rat. Subunit specific mRNAs show differential regulation. The levels of the alpha-, gamma- and delta-subunit specific mRNAs decrease steadily after birth, while the beta- and epsilon-subunit mRNAs increase transiently and then decrease. The adult pattern of subunit specific mRNA levels is reached at 4-6 weeks postnatally. The content of gamma- and epsilon-subunit mRNA changes in a reciprocal fashion during the first 2 postnatal weeks, supporting the view that differential regulation of gamma- and epsilon-subunit mRNA during development is one mechanism mediating the appearance of the adult, epsilon-subunit containing, subtype of end-plate channel. Denervation of neonatal muscle increases the levels of all subunit specific mRNAs during further development. It prevents the postnatal decrease in gamma-subunit mRNA and enhances the initial increase in epsilon-subunit mRNA. This makes it appear that the epsilon-subunit gene is less sensitive to regulation by the nerve in the postnatal period than the gamma-subunit gene. PMID- 2914621 TI - cDNA cloning and nucleotide sequence of rat muscle-specific enolase (beta beta enolase). AB - The nucleotide sequence of rat muscle-specific enolase cDNA was determined by sequencing three cDNA clones encoding this enolase isozyme. The nearly full length cDNA consists of 13-bp 5'- and 84-bp 3'-noncoding regions and a poly(A) tail in addition to a 1302-bp coding region encoding a polypeptide composed of 434 amino acid residues. The deduced primary structure of this enolase isozyme is about 80% similar to those determined previously for rat neuron-specific and non neuronal enolase isozymes. Southern blot analysis suggested strongly the existence of a single copy of the muscle-specific enolase gene per haploid genome. The mRNA for this enolase isozyme was detected in rat skeletal muscle on day 1 after birth and its level increased rapidly during 10-30 days after birth without any change in its size (1500 bases). PMID- 2914622 TI - Characterization of the two rRNA gene operons present in Thiobacillus ferrooxidans. AB - The organization of rRNA genes from the autotrophic, acidophilic bacterium Thiobacillus ferrooxidans has been examined. Two rRNA operons were found in this microorganism by means of genomic hybridization studies. Recombinant plasmids, pTR-3 and pTR-1 that carry a portion of 16/23 S rDNA from one operon and the 5' flanking region of the second operon, respectively, were identified and characterized. PMID- 2914623 TI - Dimethyl sulfoxide modulation of diabetes onset in NOD mice. AB - Dimethyl sulfoxide (DMSO), a hydroxyl radical scavenger, is known as an immunosuppressive agent and can reduce autoantibody levels in experimental autoimmune diseases. Because classic diabetogens damage the DNA and membrane of the beta-cell by the generation of free radicals, the purpose of these investigations was to determine whether the intake of DMSO or its derivatives methylsulfonylmethane (MSM) and dimethylsulfide (DMS) could prevent the expression of autoimmune diabetes in the spontaneously diabetic NOD mouse. DMSO (2.5%), MSM (2.5%), and DMS (0.25%) were added to the drinking water of female NOD mice immediately after weaning. Control animals were maintained on regular drinking water. The presence of overt diabetes was monitored from the age of 2 mo by weekly urinary glucose testing until the animals either became overtly glucosuric or were greater than 240 days of age. In contrast to what we expected, DMSO (2.5%) markedly increased the rate at which the animals expressed overt diabetes (P less than .0004, log-rank test). MSM had no effect, whereas DMS reduced the incidence and rate of diabetes onset. When DMSO (2.5%) was administered to male NOD mice and control strains of mice (BALB/c and ICR), the control group did not develop glucosuria or insipidus, whereas DMSO increased the incidence of diabetes in the male NOD mice from 21 to 79%. In contrast, when DMSO was fed to female NOD mice on a purified AIN-76 diet, diabetes onset was reduced to 36%. We conclude that DMSO accelerates the uptake of dietary diabetogens into the beta-cell of genetically susceptible animals (NOD mice). The protective effect of the purified diet in such animals may be due to a lack of putative diabetogens in purified diet, or alternatively, the diet itself contains factor(s) that protect the beta-cell from autoimmune attack and/or destruction. PMID- 2914624 TI - Total gastrectomy and small intestinal cholesterol synthesis in diabetic rats. AB - Cholesterol synthesis is increased two- to threefold in the small intestine of diabetic rats. We have observed, in three separate experiments, that the characteristic increase in small intestinal cholesterol synthesis (SICS) in diabetic rats was prevented by total gastrectomy. Food intake was increased twofold, and the small intestine hypertrophied in the gastrectomized diabetic animals. In normal animals, total gastrectomy resulted in only a very small increase in intestinal cholesterol synthesis. In hyperphagic lactating animals, total gastrectomy did not prevent the characteristic increase in SICS that is usually observed in this hyperphagic model. These results indicate that the effects of total gastrectomy on preventing an increase in SICS are relatively specific for the diabetic state. The mechanism by which total gastrectomy prevents the increase in intestinal cholesterol synthesis in diabetic animals is unknown. Vagotomy did not prevent the typical increase in intestinal synthesis in diabetic animals. Additionally, selectively removing either the antrum or fundus of the stomach did not prevent the increase in SICS in diabetic animals, indicating that the inhibition requires the removal of the entire stomach. It can be speculated that the stomach produces a substance that induces the increase in SICS observed in diabetic animals and that total gastrectomy removes this stimulatory substance. PMID- 2914625 TI - Effects of streptozocin-induced diabetes on glucose metabolism and lactate release by isolated fat cells from young lean and older, moderately obese rats. AB - Streptozocin-induced diabetes (STZ-D) was produced in male Wistar rats at two stages of development: young, lean rats, weighing 150-220 g (6-8 wk), and older, moderately obese rats, weighing 450-500 g (6-8 mo). A comparable degree of hyperglycemia (420-500 mg/dl) without ketosis was generated by injection of 50 mg/kg i.v. STZ for young, lean rats and 30 mg/kg i.v. for older, fatter rats. The animals were killed 8-11 days after injection. Insulin binding by the isolated adipocytes of both groups was not significantly altered on a per-cell basis by the presence of diabetes. Total adipocyte glucose metabolism, both basal and insulin stimulated, was reduced (63 and 88%, respectively) by the induction of diabetes in young, lean rats. In contrast, the induction of diabetes in the older, moderately obese rats had no suppressive effect on total glucose metabolism by their fat cells. Diabetes increased the relative conversion of glucose to lactate by fat cells from both groups of rats, but in absolute terms, the fat cells from the obese diabetic rats produced significantly more lactate from glucose than cells from the lean diabetic rats, both in the absence and presence of insulin. Diabetes did not alter the glucose concentration at which peak insulin response occurred in either group. We conclude that STZ-D in rats, at different stages of development and degrees of adiposity, results in quantitatively different alterations of adipocyte metabolism, which appear to be postreceptor in nature and result in an increase in glucose conversion to lactate. PMID- 2914626 TI - IOM study finds NIH's intramural program 'invaluable'. Urges some administrative changes. PMID- 2914627 TI - Danazol therapy renders red cells resistant to osmotic lysis. AB - Danazol, an attenuated androgen, is useful in endometriosis, idiopathic thrombocytopenic purpura (ITP), and autoimmune hemolytic anemia (AIHA). However, its mechanism of action is unknown. We investigated the possibility that danazol affects cell membranes directly. Red cell osmotic fragility was studied in patients receiving danazol. A significant decrease in osmotic fragility was observed. Accompanying the change, peripheral blood smears showed many target cells and electron microscopy revealed extra folds in erythrocyte membranes. Twenty-two patients were studied prospectively before and after danazol. Osmotic fragility decreased significantly (P less than 0.001) in 1 month of therapy and progressed with further treatment. A rebound increase (P less than 0.01) was observed in 1 month after discontinuation of danazol among 16 patients. Incubation experiments showed that danazol-induced changes are not reversed with normal sera. Patient sera did not induce the changes in normal red cells. Danazol in vitro protected red cells from osmotic lysis at low concentrations but enhanced lysis at high concentrations. We suggest that danazol alters red cell membranes directly to increase their surface area, inducing target cell formation and increasing their resistance to osmotic lysis. PMID- 2914629 TI - This is FASEB. The financial structure. PMID- 2914628 TI - Hepatocyte function and extracellular matrix geometry: long-term culture in a sandwich configuration. AB - Adult rat hepatocytes cultured in a collagen sandwich system maintained normal morphology and a physiological rate of albumin secretion for at least 42 days. Hepatocytes cultured on a single layer of collagen gel essentially ceased albumin secretion within 1 wk but could recover function with the overlay of a second layer of collagen gel. This culture configuration more closely mimics the hepatocytes' in vivo environment and provides a simple method for their long-term maintenance. PMID- 2914630 TI - Colloquium on scientific authorship: rights and responsibilities. AB - The Colloquium on Scientific Authorship was held at the National Institutes of Health (NIH) at a time of extraordinary scrutiny by the public of the ethics of scientists, as represented by intense interest of the press and the Congress of the United States. Indeed, several regulations dealing with scientific misconduct have been proposed during the last year in the Federal Register, and new legislation has been proposed in the Congress. As a result of these concerns, conferences have been organized by the Institute of Medicine, the American Association for the Advancement of Science/American Bar Association, the Council of Biology Editors, and other groups. The colloquium at NIH, which was held May 31, 1988, and sponsored by the Intramural Scientists, focused on publication practices, especially multiple authorship, as contributing to perceived difficulties. The participants suggested various changes in conventions related to authorship that might help prevent future problems. PMID- 2914632 TI - Federation of American Societies for Experimental Biology. 73rd annual meeting. New Orleans, Louisiana, March 19-23, 1989. Part I. Abstracts 1-4022. PMID- 2914631 TI - Animal nutrition. PMID- 2914633 TI - Federation of American Societies for Experimental Biology. 73rd annual meeting. New Orleans, Louisiana, March 19-23, 1989. Part II. Abstracts 4023-6650. PMID- 2914634 TI - Sensitivity of the esophageal mucosa to pH in gastroesophageal reflux disease. AB - To determine the relation between the sensation of pain in gastroesophageal reflux and the pH of the refluxate, we studied 25 individuals with symptomatic gastroesophageal reflux and positive Bernstein tests. We quantitatively assessed the sensitivity of the esophageal mucosa to pain associated with the intraesophageal infusion of eight different HCl solutions (pH 1, 1.5, 2, 2.5, 3, 4, 5, and 6). Test solutions were infused at 8 ml/min through an eight-lumen catheter with the orifices placed 5 cm above the lower esophageal sphincter. Each subject received all eight solutions in a double-blind randomized fashion. The time-to-pain onset increased with increasing pH; i.e., there was a highly significant difference between the time-to-pain and pH (p less than 0.001), with the time-to-pain significantly longer with increasing pH (r = 0.77). In addition to more rapid onset of pain, all subjects experienced pain with the pH 1 and 1.5 solutions, 80% had pain with the pH 2.0 solution, and half had pain with solutions of pH 2.5-6. Fifteen of these subjects underwent 24-h pH monitoring and these tests were examined for factors associated with pain. Only 64% of all pain episodes were associated with a pH drop of less than 4; the lowest pH obtained was not different between episodes with and without pain. Reflux episodes resulting in pain were significantly longer than those without pain and were more often associated with a recently preceding painful episode. Overall, none of the data from the 24-h pH monitoring was useful for predicting pain. The acid infusion studies and the 24-h pH data, taken together, suggest episodes of pain sensitize the patient for subsequent pain. PMID- 2914635 TI - Molecular heterogeneity of human motilinlike immunoreactivity explained by the processing of prepromotilin. AB - Results of studies on the molecular forms of canine motilin suggest that this hormone might be synthesized as a higher molecular weight precursor, as is the case for most other biologically active peptides. Chromatographic analysis of human duodenal mucosa extracts and of human serum, using motilin-specific antibodies, also shows the presence of multiple forms of motilinlike immunoreactivity. Cell free translation of human duodenal messenger ribonucleic acid (mRNA) and immunoprecipitation of nascent peptides with motilin antibodies confirm that motilin is synthesized as a 14-15-kilodalton polypeptide precursor. Sequence of the human intestinal motilin complementary deoxyribonucleic acid (cDNA) demonstrates that this precursor bears a 25-amino acid signal peptide, a single dibasic cleavage site immediately following the 22 amino acids of human motilin, and a 65-amino acid polypeptide (motilin-related peptide) following this dibasic processing site. Southern analysis of human genomic kilobases DNA demonstrates that only one motilin gene is contained within 3.5-4 of human genomic DNA. Northern analysis of human intestinal RNA reveals one species of motilin mRNA of an estimated 700 nucleotides in length. These results suggest that (a) only one gene encodes the synthesis of human motilin in the different tissues where this polypeptide is synthesized; (b) human intestinal motilin is translated from one mRNA species and the resulting precursor is processed within the duodenal mucosa by sequential proteolytic cleavage first at a site within the motilin-related peptide, which results in the liberation of a 6-kilodalton form of motilinlike immunoreactivity, and then at the dibasic amino acid cleavage site, thus freeing motilin 22 from its precursor. PMID- 2914636 TI - Activated aluminum complex derived from solubilized antacids exhibits enhanced cytoprotective activity in the rat. AB - Removing the buffering capacity of aluminum-containing antacids by acidification greatly increased their cytoprotective activity over the parent antacid. Commercially available antacids were acidified with 6 N HCl. Peak mucosal protective activity occurred at pH 2.5, and declined at lower pH. At pH 2.5, the antacid suspensions became solubilized and no acid-neutralizing capacity remained. This solution was named activated aluminum complex. Based on aluminum ion content, each aluminum-containing antacid suspension tested demonstrated a comparable increase in potency on acidification against ethanol-induced lesions. HCl (pH 2.5) was inactive against ethanol-induced lesions. At cytoprotective doses, activated aluminum complex did not cause gastric lesions when orally administered by itself, demonstrating that it is not acting as a local mucosal irritant. The data suggest that solubilization of aluminum-containing antacids in acidic medium enhances their mucosal protective activity, probably by releasing an activated species of aluminum ion reported to be a hexaaquoaluminum cation. PMID- 2914637 TI - Characterization of the human colon carcinoma cell line (Caco-2) as a model system for intestinal epithelial permeability. AB - Caco-2 cells develop morphologic characteristics of normal enterocytes when grown on plastic dishes or nitrocellulose filters. The purpose of this study was to determine whether Caco-2 cells undergo similar differentiation when grown on Transwell polycarbonate membranes, and to study the suitability of Caco-2 monolayers as an intestinal epithelial transport model system. Transepithelial electrical resistance values after confluence were 173.5 omega.cm2 and remained unchanged through day 17. Permeabilities to the water-soluble fluid-phase markers that do not permeate the membrane, Lucifer yellow CH, [14C]inulin, [14C]polyethylene glycol, and [3H] dextran were less than 0.25% of the administered amount per hour after day 10. Qualitative evaluation of uptake and permeability to horseradish peroxidase confirmed the similarity in uptake and barrier properties between this cell system and the small intestinal epithelial layer. We conclude that Caco-2 cells grown on collagen-coated polycarbonate membranes should represent a valuable transport model system for the small intestinal epithelium. PMID- 2914638 TI - Immunoproliferative small intestinal disease without alpha-chain disease: a pathological study. AB - Biopsy specimens taken during exploratory laparotomy provided the material for a pathological study of 23 cases of nonsecreting immunoproliferative small intestinal disease (Mediterranean lymphomas without alpha-chain disease). The distinctive pathological feature of immunoproliferative small intestinal disease, i.e., a diffuse lymphoid infiltration, was present in the mucosa and submucosa of all or a major part of the small intestine. It was composed of a low- or intermediate-grade malignant lymphoid proliferation associated in 19 of 23 cases with benign-appearing follicular lymphoid structures. These follicular figures were surrounded and partially destroyed by the lymphoma cells. This association strongly resembles the newly described non-Hodgkin's lymphoma entities of perifollicular or parafollicular cell origin. Gross tumors of the small intestine were found in association with the diffuse lymphoid infiltration in 10 cases. They often constituted foci of lymphoma with a higher grade of malignancy. Mesenteric lymph node involvement was frequent and generally in direct ratio to the severity of intestinal involvement. A comprehensive study of the lesions observed in these cases led to the hypothesis that nonsecreting immunoproliferative small intestinal disease could result from the malignant change of perifollicular B cells; during an initial period the tumoral cells retain circulating and homing properties that explain their infiltrative and extensive method of spreading. The possible subsequent emergence of more aggressive subclones of noncirculating malignant cells could then explain the associated inconstant fungating tumor foci. Further studies using more sophisticated immunohistochemical techniques are necessary to establish the meaning of the hyperplastic lymphoid follicles, the possible etiologic role of benign nodular hyperplasia, the exact identification of the tumor cells, and the relationship of nonsecreting immunoproliferative small intestinal disease to closely related alpha-chain disease. PMID- 2914639 TI - Alterations in serum immunoglobulin G subclasses in patients with ulcerative colitis and Crohn's disease. AB - We have examined the concentration of immunoglobulin G (IgG) subclass antibodies in the sera of 27 patients with ulcerative colitis and 21 patients with Crohn's disease as well as in 11 normal controls and 11 patients with systemic lupus erythematosus. In comparison with a control mean serum IgG1 concentration of 5173 micrograms/ml, patients with ulcerative colitis exhibited a significantly increased mean serum concentration of 7924 micrograms/ml (p less than 0.05), whereas patients with Crohn's disease had a near normal mean serum IgG1 level of 5898 micrograms/ml. In contrast, control sera had a mean IgG2 level of 2477 micrograms/ml and ulcerative colitis sera had a similar IgG2 level of 2269 micrograms/ml, whereas Crohn's disease sera had a significantly increased mean IgG2 level of 5111 micrograms/ml (p less than 0.05). Patients with systemic lupus erythematosus, like those with ulcerative colitis, had a markedly elevated serum IgG1 level of 15,594 micrograms/ml (p less than 0.001) without a significantly increased IgG2 serum level (3271 micrograms/ml). Neither ulcerative colitis nor Crohn's disease sera exhibited altered levels of IgG3 or IgG4. These data show that alterations in IgG subclass concentrations occur in the sera of patients with active, untreated inflammatory bowel disease, similar to the previously noted changes in the IgG subclasses secreted by lymphocytes from involved inflammatory bowel disease intestinal specimens. PMID- 2914640 TI - Optical performance of electronic imaging systems for the colon. AB - Electronic (video) endoscopes are a significant new development in gastroenterology, offering the potential of enhanced teaching and permanent storage of pictorial data. The primary concern of gastroenterologists is the resolution and color performance of these instruments, as these parameters have important bearings on the ability to discern pathological changes in mucosa. We sought to determine the resolution and color capabilities of electronic colonoscopes and compare them with a conventional fiber colonoscope. Resolution was determined using a standard test chart at various distances and the number of picture elements (a measure of resolution) was calculated. The mean number of picture elements was Fujinon (219), Fiber (172), Pentax (169), Toshiba (142), Olympus (140), and Welch Allyn (133). In close focus examination (target distances less than 1 cm), the Fujinon and Toshiba endoscopes had significantly higher resolution than the other instruments. Color was measured quantitatively using a standard color chart and a color analyzer. Color polygons were plotted for each endoscope on a reference chromaticity diagram. All systems had an acceptable overall performance but color was undersaturated with some systems. The optical performance of electronic endoscopes has improved considerably since the inception of electronic endoscopy. PMID- 2914641 TI - Effect of proctocolectomy for chronic ulcerative colitis on the natural history of primary sclerosing cholangitis. AB - The effect of proctocolectomy on the primary sclerosing cholangitis that frequently is associated with chronic ulcerative colitis in patients with both conditions is unknown. We have studied prospectively the progression of clinical, biochemical, cholangiographic, and hepatic histologic features in 45 patients with both primary sclerosing cholangitis and chronic ulcerative colitis to compare these variables in the 20 patients who had undergone proctocolectomy with the 25 who had not. The two groups were similar initially with regard to clinical, biochemical, cholangiographic, and hepatic histologic findings. All patients were followed for a minimum of 1 yr and overall duration of follow-up was similar in both groups (4.1 vs. 3.9 yr). Clinically, new onset of hepatomegaly, splenomegaly, esophageal varices, and ascites did not differ in patients with and without proctocolectomy. Biochemically, the serial changes in bilirubin, alkaline phosphatase, aspartate aminotransferase, prothrombin time, and albumin were similar. Histologic progression on liver biopsy did not differ between groups, nor did changes on serial cholangiograms. Proctocolectomy also had no effect on survival. We conclude that proctocolectomy for chronic ulcerative colitis has no beneficial effect on the primary sclerosing cholangitis in patients with both diseases. PMID- 2914642 TI - Hapten-induced model of chronic inflammation and ulceration in the rat colon. AB - We have developed a simple and reproducible rat model of chronic colonic inflammation by the intraluminal instillation of a solution containing a "barrier breaker" and a hapten. Administration of the hapten 2,4,6-trinitrobenzenesulfonic acid (5-30 mg) in 0.25 ml of 50% ethanol as the "barrier breaker" produced dose dependent colonic ulceration and inflammation. At a dose of 30 mg, trinitrobenzenesulfonic acid/ethanol-induced ulceration and marked thickening of the bowel wall persisted for at least 8 wk. Histologically, the inflammatory response included mucosal and submucosal infiltration by polymorphonuclear leukocytes, macrophages, lymphocytes, connective tissue mast cells, and fibroblasts. Granulomas were observed in 57% of the rats killed 3 wk after induction of inflammation. Langhan's-type giant cells were also observed. Segmental ulceration and inflammation were common. The characteristics and relatively long duration of inflammation and ulceration induced in this model afford an opportunity to study the pathophysiology of colonic inflammatory disease in a specifically controlled fashion, and to evaluate new treatments potentially applicable to inflammatory bowel disease in humans. PMID- 2914643 TI - Ileal ecology after pouch-anal anastomosis or ileostomy. A study of mucosal morphology, fecal bacteriology, fecal volatile fatty acids, and their interrelationship. AB - Ileal mucosal morphology, fecal bacteriology, fecal volatile fatty acids, and their interrelationships were studied in 15 patients with an ileal pouch-anal anastomosis and 14 patients with an ileostomy after proctocolectomy for ulcerative colitis. Pouch effluent, compared with ileostomy effluent, had a greater ratio of anaerobes to aerobes (p less than 0.05), and greater numbers of Bacteroides (p less than 0.01) and Bifidobacteria (p less than 0.05). Fecal volatile fatty acids, products of anaerobic bacterial fermentation, were also increased in pouch effluent compared with ileostomy effluent (propionate, p less than 0.05; butyrate, p less than 0.01). Mucosal change in the pouches showed no significant correlation with frequency of defecation, completeness of emptying, or pouch design, but the degree of villous atrophy was correlated with the number of Bacteroides (rs = 0.93, p less than 0.01) and with fecal butyrate (rs = 0.68, p less than 0.05). Fecal propionate was significantly correlated with the percentage of stool retained after defecation (rs = 0.82, p less than 0.01). These findings indicate that the bacterial ecology of ileal pouches has an important influence on the morphology of their mucosal lining. PMID- 2914644 TI - Ablation of rabbit liver, stomach, and colon with a pulsed holmium laser. AB - A pulsed holmium laser (wavelength 2.1 microns, pulse duration 250 microseconds) was used to ablate rabbit liver, stomach, and colon in vivo. Microscopic examination of the tissues revealed zones of thermal damage extending 0.5-1.0 mm from ablation sites. In addition, ablation rates were measured using a mass loss technique and found to increase linearly with delivered radiant exposure. The threshold radiant exposure for ablation was calculated to be 50 J/cm2 with a heat of ablation of 7000 J/cm3. Because the holmium laser produces less thermal necrosis than current endoscopic laser systems, such as the continuous-wave neodymium:YAG laser, and because the ablation rate can be precisely controlled, the holmium laser shows promise as an alternative method for endoscopic removal of tissue. PMID- 2914645 TI - Role of pancreatic enzymes and their substrates in autodigestion of the pancreas. In vitro studies with isolated rat pancreatic acini. AB - Intrapancreatic activation of proteases is believed to play a major role in the pathogenesis of acute necrotizing pancreatitis. Several authors have questioned, however, the central role of trypsin in autodigestion of the pancreas. To clarify the direct effects of pancreatic enzymes and other related factors on acinar cells, we used the model of isolated pancreatic acini. Acini were prepared from male Wistar rats by collagenase digestion. Protein synthesis was measured by incubation of acini with [35S]methionine. Acini were resuspended thereafter in fresh buffer and further incubated for 30-90 min under various conditions [e.g., with pancreatic homogenates, ascites (from rats with pancreatitis induced by sodium taurocholate), pure pancreatic enzymes, and other factors]. The percentage of release of newly synthesized proteins into the culture medium was regarded as a biochemical parameter of cellular integrity. A morphologic score of cellular integrity was obtained via light microscopic evaluation of acini at the end of the various incubations by measuring the degree of cell lysis, loss of cell granules, ballooning, formation of vacuoles, and karyopyknosis. When normal [35S]methionine-labeled pancreatic acini were incubated with various factors, the percentage of release of labeled proteins into the medium was as follows: incubation with HEPES/Ringer's buffer, 1.8%; hemorrhagic pancreatic ascites, 3.8%; pancreatic homogenates, 2.0%; lipase, 1.8%; phospholipase A2, 3.0%; phospholipase A2 + lecithin, 3.2%; trypsin, 2.5%; 5% olive oil, 1.8%; ascites + olive oil, 78.3%; ascites + homogenized epididymal fat, 79.9%; lipase + olive oil, 32.0%; pancreatic homogenates + olive oil, 28.0%; diolein, 2.65%; and oleic acid, 62.9%. The cellular release of radiolabeled proteins showed an inverse correlation with cellular integrity as shown by light microscopy. We postulate that interstitial release of degradation products from triglycerides by lipase causes cellular disruption. Whereas phospholipase A2 and proteases do not seem to be very harmful in the early phases of cellular damage, lipase may play a major role in acute necrotizing pancreatitis. PMID- 2914646 TI - Gallbladder motility before and after extracorporeal shock-wave lithotripsy. AB - To determine whether extracorporeal shock-wave lithotripsy of gallbladder stones alters gallbladder motility, gallbladder contraction in response to intravenous cholecystokinin was investigated by ultrasound. Twenty-one patients with symptomatic gallstones were studied before and after shock-wave lithotripsy, 12 with and 9 without concomitant litholytic therapy (combination of ursodeoxycholic acid and chenodeoxycholic acid). Gallbladder emptying was significantly delayed and less complete in both groups of patients before shock-wave treatment (with bile salts: residual volume, 51% +/- 10% and half-ejection time, 40 +/- 5 min; without bile salts: residual volume, 46% +/- 7%; half-ejection time, 30 +/- 4 min) compared with healthy controls (residual volume, 15% +/- 4%; half-ejection time, 18 +/- 2 min). Gallbladder motility was not altered in either group 1 day and 1 yr after lithotripsy. The findings indicate (a) that extracorporeal shock wave lithotripsy has no immediate or long-term adverse effects on gallbladder motility and (b) that the defect of gallbladder motility associated with gallstone disease is not abolished by removal of the stone. PMID- 2914647 TI - Effect of liver regeneration on hepatic cytochrome P450 isozymes and serum sex steroids in the male rat. AB - Partial hepatectomy in male adult rats results in raised serum estrogen levels and demasculinization of certain aspects of hepatic metabolism. Some constitutive forms of hepatic cytochrome P450 are sex-dependent and we have previously demonstrated demasculinization of cytochrome P450 isozyme distribution in a rat model of cirrhosis. As liver regeneration is an integral component of cirrhosis, the present study was performed to ascertain the effects of regeneration on hepatic cytochrome P450 isozyme composition and serum sex steroid concentrations. Adult male rats were subjected to 65% partial hepatectomy or sham-operation. The position-specific hydroxylation of androstenedione was used as a probe for isozyme activity. Serum sex steroids, hepatic enzymes, and hepatic deoxyribonucleic acid synthesis were measured in groups of animals at 0, 6, 24, 48, and 72 h. By 72 h total microsomal cytochrome P450 in partially hepatectomized animals had fallen to 66% of that in nonoperated animals. In both partially hepatectomized and sham-operated animals, androstenedione 7 alpha- and 16 beta-hydroxylase activity returned to preoperative levels by 48 h. However, the male-specific androstenedione 16 alpha- and 6 beta-hydroxylase activities and aromatase activity remained suppressed in partially hepatectomized liver. Serum estradiol increased eightfold in partially hepatectomized rats and peaked at 6 h followed by a gradual fall to control values. No change in serum estradiol was observed in sham-operated animals. We conclude that demasculinization of hepatic oxidative metabolism occurs in regenerating rat liver. The early rise in serum estradiol is consistent with a role for this hormone in the changes in cytochrome P450 observed, and possibly the process of liver regeneration. PMID- 2914648 TI - Calcium carbonate saturation in human pancreatic juice: possible role of ductal H+ secretion. AB - Saturation with calcium carbonate was measured in human pancreatic juice anaerobically collected for diagnostic purposes in 15 patients who were ultimately found not to have pancreatic disease. Bicarbonate, PCO2, proteins, and total and ionized calcium were measured in samples collected every minute during a 20-min period after intravenous administration of secretin (1 U/kg) and, 10 min later, caerulein (75 ng/kg). All samples were supersaturated with calcium carbonate. The first sample (washing-out sample) contained the highest concentrations of ionized calcium (Ca2+) and proteins but was least supersaturated with calcium carbonate. Washing-out samples also differed significantly from samples under caerulein by having a lower pH (7.52 +/- 0.30) and higher PCO2 (103.1 +/- 32.20 mmHg) versus 8.22 +/- 0.15 and 38.4 +/- 4.5 mmHg, respectively. Values of PCO2 increased and bicarbonate concentration decreased linearly with protein concentration in washing-out samples but not under hormonal stimulation. This suggests that a concentration of pancreatic juice occurs in pancreatic ducts in association with luminal H+ secretion and CO2 formation, which results from bicarbonate neutralization. During stimulation, ionized calcium concentration increased with protein concentration without any change of PCO2, so that supersaturation was more pronounced under caerulein than under secretin stimulation. Disturbances of the ductal concentration of pancreatic juice during interdigestive periods could be important for pancreatic stone formation in humans. PMID- 2914649 TI - Effect of body temperature on brain edema and encephalopathy in the rat after hepatic devascularization. AB - Brain edema is a fatal complication of fulminant hepatic failure and its pathogenesis remains unclear. To determine its presence in a model of ischemic hepatic failure, rats were subjected to a portacaval anastomosis followed by hepatic artery ligation. Brain water was measured using the sensitive gravimetric method. Preliminary studies revealed marked hypothermia in devascularized animals kept at room temperature (26.9 degrees +/- 2.8 degrees C). An additional group of devascularized rats was kept in an incubator. As expected for hypothermia, such animals had a lower arterial pressure and heart rate; the duration of encephalopathy was markedly prolonged. Water content of the cortical gray matter was only increased in normothermic devascularized rats: 80.14% +/- 0.31%, normal; 80.06% +/- 0.22%, portacaval shunt only; 80.42% +/- 0.26%, devascularized at room temperature; 81.29% +/- 0.38%, devascularized at controlled temperature (p less than 0.001). Such differences could not be detected using the dry-weight technique in whole cerebral hemispheres. Astrocyte changes in the cortical gray matter were noted in both edematous and nonedematous devascularized groups, coupled with the presence of vesicles containing horseradish peroxidase in the endothelial capillary cell. This suggests that in this model, brain edema may be due to both a cytotoxic mechanism and changes in the permeability of the blood brain barrier. Future studies with this widely used model will require strict control of temperature to allow interpretation of experimental results. A therapeutic role for hypothermia in the management of brain edema deserves further attention. PMID- 2914650 TI - Increased procoagulant activity of peripheral blood monocytes in human and experimental obstructive jaundice. AB - We studied the procoagulant activity of peripheral blood monocytes in 41 patients with severe obstructive jaundice and in 27 nonjaundiced control patients using a one-stage clotting assay. Mononuclear cells from jaundiced patients, tested immediately after isolation, expressed low levels of procoagulant activity, which were, however, significantly higher than in cells from controls (p less than 0.01). In addition, after incubation in short-term cultures with and without endotoxin, these cells generated more procoagulant activity than did the control ones (p less than 0.001). No significant difference in procoagulant activity was found between patients with and without malignancy in either group. The relief of biliary obstruction resulted in the reduction of both serum bilirubin levels and monocyte procoagulant activity. Endotoxin-induced monocyte procoagulant activity was about threefold higher in the jaundiced patients who died than in the survivors (p less than 0.001). In rabbits made icteric by bile duct ligation and separation (15 days), the endotoxin-induced monocyte procoagulant activity was markedly increased as compared with sham-operated animals (p less than 0.005). In all instances, procoagulant activity was identified as tissue factor. The increased capacity of mononuclear phagocytes to produce procoagulant activity might help explain the activation of blood coagulation in severe obstructive jaundice. PMID- 2914651 TI - Pancreaticobiliary ductal union in biliary diseases. An endoscopic retrograde cholangiopancreatographic study. AB - To assess whether the anatomy of the pancreaticobiliary ductal drainage into the duodenum has any relationship with biliary diseases we analyzed 259 endoscopic retrograde cholangiopancreatograms. These included 102 normal examinations (control group), 95 patients with gallstone disease, and 21 patients with carcinoma of the gallbladder. In the control group, 64 (63%) subjects had a common channel and 38 (37%) had separated openings for the common bile duct and the main pancreatic duct. By contrast, the prevalence rate of a common channel was significantly lower in gallstone disease [28 (30%); p less than 0.001]. No such difference, compared with controls, was observed in patients with carcinoma of the gallbladder. The length of the common channel in the control group (mean +/- SD, 4.7 +/- 2.5 mm) was similar to that in gallstone disease (4.6 +/- 2.6 mm). However, patients with carcinoma of the gallbladder had a significantly longer common channel (8.3 +/- 4 mm; p less than 0.001) compared with the control group. An abnormally long common channel (greater than or equal to 8 mm) was seen more frequently in carcinoma of the gallbladder (8 of 21; 38%) compared with normal subjects (3 of 102; 3%) and patients with gallstones (1 of 95; 1%); the difference was highly significant (p less than 0.001 for each). These observations suggest a close association between the anatomy of the distal ends of the common bile duct and main pancreatic duct and the development of gallstones and carcinoma of the gallbladder. PMID- 2914652 TI - Evidence that vasoactive intestinal peptide induces ductular secretion of bile in humans. AB - The effect of intravenously administered vasoactive intestinal polypeptide on bile secretion was studied in 11 patients with complete biliary drainage. After infusion of vasoactive intestinal polypeptide, bile volume increased by 65%. In the 2 patients investigated, the output of bicarbonate increased by approximately 250% and the concentration by 50%-70%. Vasoactive intestinal polypeptide thus caused a bicarbonate-rich choleresis. The output of biliary lipids was not affected by infusion of vasoactive intestinal polypeptide, whereas the concentration decreased by approximately 40%. The canalicular bile flow, measured by the clearance of [14C]erythritol, was not affected by infusion of vasoactive intestinal polypeptide. The choleretic effect of vasoactive intestinal polypeptide thus seems to occur only at the ductular level. The ductular bile flow was calculated to be stimulated threefold to fourfold. PMID- 2914653 TI - Pancreatic secretory response to intravenous caerulein and intraduodenal tryptophan studies: before and after stepwise removal of the extrinsic nerves of the pancreas in dogs. AB - In two sets of 6 dogs with gastric and pancreatic fistulas, we studied the effect of atropine (14 nmol/kg.h i.v.) on the pancreatic secretory response to intravenous caerulein and to intraduodenal perfusion with tryptophan (both given with a secretin background) before and after stepwise removal of the extrinsic nerves of the pancreas, i.e., celiac and superior mesenteric ganglionectomy alone or truncal vagotomy alone and truncal vagotomy plus celiac and superior mesenteric ganglionectomy. Atropine significantly (p less than 0.05) depressed the protein output in the basal state and in response to secretin at each stage of innervation. The incremental protein response to caerulein was not altered by the various denervation operations nor by atropine. Truncal vagotomy alone significantly decreased the incremental protein response to low (0.12, 0.37, and 1.1 mmol/h) but not high loads of tryptophan. Ganglionectomy in combination with vagotomy did not further depress the incremental protein response to low loads of tryptophan. Atropine significantly reduced the incremental protein response to low loads of tryptophan only in intact innervated animals. Ganglionectomy alone did not alter the incremental protein response to any load of tryptophan. Ganglionectomy, truncal vagotomy, and atropine did not alter basal or tryptophan stimulated levels of plasma cholecystokininlike immunoreactivity. We conclude that (a) neither the extrinsic nor the intrinsic cholinergic pancreatic nerves modulate the protein response to caerulein; (b) the sympathetic pancreatic nerves do not mediate the response to tryptophan; (c) the protein response to intraduodenal tryptophan is at least in part mediated by long, cholinergic, enteropancreatic reflexes with both afferent and efferent fibers running within the vagus nerves; and (d) release of cholecystokinin by intestinal tryptophan is not under cholinergic or splanchnic control. PMID- 2914654 TI - Role of biliary phospholipids in cholesterol gallstone formation. PMID- 2914655 TI - Generalized undifferentiated epithelioma. PMID- 2914656 TI - Spontaneous esophagotracheal fistula. PMID- 2914657 TI - Manpower in gastroenterology in the United States: a position paper of the Training and Education Committee of the AGA. PMID- 2914658 TI - Duodenal diaphragmatic lesions and nonsteroidal antiinflammatory drugs. PMID- 2914659 TI - Storage of breath H2 in vacutainer and gaseous contamination. PMID- 2914660 TI - Food ingestion as a provocative manometric test for esophageal dysfunction. PMID- 2914662 TI - Going overboard with mini-mental exams. PMID- 2914661 TI - Does early antisecretory treatment limit ulcer development? PMID- 2914663 TI - Highlights of the 40th Institute on Hospital and Community Psychiatry. PMID- 2914664 TI - NIMH report. Carbamazepine: treatment option for bipolar patients. PMID- 2914665 TI - An extramural training program in psychopharmacology: one model for a state system. PMID- 2914666 TI - The management of HIV infection in state psychiatric hospitals. AB - Patients with AIDS and related illnesses are entering state mental hospitals in increasing numbers. State hospitals in New York City generally did not plan for patients infected with human immunodeficiency virus (HIV) until the first patient appeared; however, over the past five years, approaches to managing these patients have evolved in the areas of admission policies, in-hospital care, and discharge planning. Strengthening infection control procedures through the adoption of universal precautions was the most straightforward aspect of in hospital care. Testing for HIV and confidentiality of the test results proved most controversial. Clinical leaders urged that testing be done only with pre- and posttest counseling and only if the patient has symptoms of HIV infection, has requested the test, or has exposed others to infection. The authors describe these and other policies addressing medical care, restraint and seclusion, sexual behavior, and education and training. PMID- 2914667 TI - Warning third parties at risk of AIDS: APA's policy is a barrier to treatment. AB - The American Psychiatric Association has adopted a policy stating that psychiatrists may warn third parties who are placed at risk by the behavior of a patient infected with human immunodeficiency virus (HIV). The author argues that although the policy appears reasonable and has well-established precedent, the public will ultimately be better served if HIV-infected patients are assured absolute confidentiality. He contends that the Tarasoff decision is not directly applicable to most HIV-infected patients, that education alone will not be sufficient to deter some infected patients from placing others at risk, that additional psychiatric interventions will be necessary to reduce the high-risk behaviors of those individuals, and that APA's policy will prevent many from seeking treatment. PMID- 2914668 TI - Warning third parties at risk of AIDS: APA's policy is a reasonable approach. AB - The author argues that the American Psychiatric Association's AIDS policy on confidentiality and disclosure provides reasonable guidelines for psychiatrists struggling to balance their obligation to maintain the confidentiality of individual patients infected with human immunodeficiency virus (HIV) with their obligation to protect the community's health. The policy states that notification of third parties who may be exposed to infection through the behavior of an HIV positive patient is ethically permissible if the psychiatrist has exhausted efforts to work with the patient to terminate behavior that places others at risk and if the patient understands the limits of confidentiality. The author points out that judicious notification is within the medical tradition that includes disclosure of a patient's dangerousness in situations involving infectious diseases such as tuberculosis and is supported by the duty-to-warn precedent set by the Tarasoff decision. PMID- 2914669 TI - Characteristics of community support program clients in 1980 and 1984. AB - Results from a survey of 1,053 clients enrolled in the community support program in 1984 were compared with data on 1,471 clients enrolled in 1980. In 1984 the percentages of males and blacks treated was larger than in 1980, and clients made increased use of private homes and apartments and relied less on supported living arrangements. Both the percentage of clients receiving federal income supports and clients' median income as a percentage of the national median declined between 1980 and 1984. Fewer clients with schizophrenia and more clients with affective disorders were treated in 1984 than in 1980, probably due to implementation of DSM-III. Nationwide, the number of clients in the program grew from 4,288 in 1980 to more than 350,000 in 1984. The preponderance of schizophrenia, unemployment, and history of hospitalization in the 1984 cohort suggests the program is meeting its goal of treating the most severely mentally disabled. PMID- 2914670 TI - A community of buddies: support groups for veterans forced into early retirement. AB - Ongoing support groups for veterans who have made a poor adjustment to involuntary early retirement are offered by a mental hygiene clinic in a Veterans Administration hospital. Most of the veterans have been forced to retire for medical reasons. The groups are intended to strengthen their support systems and to reduce the negative psychosocial consequences of involuntary early retirement, such as isolation, boredom, depression, and impaired social relationships. A survey of group members indicated their functioning had improved after group participation. They reported better mental health, improved social relationships, higher activity levels, and greater satisfaction with retirement. PMID- 2914671 TI - A comparison of two crisis housing alternatives to psychiatric hospitalization. AB - This study compared outcomes for demographically matched clients four months after their admission to two short-term crisis programs. The programs provided crisis housing and case management services as alternatives to psychiatric hospitalization for clients with severe and persistent mental illness. One program met housing needs by purchasing shelter in hotels and boarding houses, and the other provided lodging in an eight-bed crisis house. In both programs, two-thirds of the clients avoided hospitalization during four-month follow-up, and both programs were effective in stabilizing clients' housing and financial situations. Clients in the purchase-of-housing program showed an increase in substance abuse problems at follow-up. Average client costs were similar in the two programs. A critical program difference was the substantially higher staff turnover in the crisis house, which was later replaced with scattered-site crisis housing. PMID- 2914672 TI - The hospitalizable patient as commodity: selling in a bear market. PMID- 2914673 TI - Differences between men and women with multiple personality disorder. PMID- 2914674 TI - How psychotherapy can help the schizophrenic patient. PMID- 2914675 TI - Case management. PMID- 2914676 TI - Drug noncompliance. PMID- 2914677 TI - Civil commitment. PMID- 2914678 TI - Adverse selection hurts competition among insurers. PMID- 2914679 TI - Trauma center closings threaten other hospitals. PMID- 2914680 TI - Hospitals seek role as venture capitalists. PMID- 2914681 TI - It's systematic, automatic quality at Humana. PMID- 2914682 TI - Breaking the medical gridlock. PMID- 2914683 TI - Enter exclusive contracts for right reasons. PMID- 2914684 TI - EPA plans to revise medical waste regulations. PMID- 2914685 TI - Asbestos claims to be processed. PMID- 2914686 TI - Marketing mammography: education key. PMID- 2914687 TI - Hospitals lag in human resources spending. PMID- 2914688 TI - Hospitals on hold for data bank protocols. PMID- 2914689 TI - Construction trends in health care. PMID- 2914690 TI - The first defense: improve MD productivity. Interview by Michele Robinson. PMID- 2914691 TI - Court decision offers price-fixing guidelines. PMID- 2914692 TI - Annual forecast shows where to beef up budgets. PMID- 2914693 TI - Endurance is key to successful turnaround. PMID- 2914694 TI - Risk managers need clout, backup to cut losses. PMID- 2914695 TI - Hospitals still prefer in-house data management. PMID- 2914696 TI - Networking is key to professional development. PMID- 2914697 TI - The pathologist as an educator: time for reappraisal. PMID- 2914698 TI - Minimal pathologic changes of the lung and asbestos exposure. AB - A group of 199 autopsy subjects was investigated for minimal pathologic pulmonary changes possibly resulting from asbestos exposure. According to the standards proposed by the Pneumoconiosis Committee of the College of American Pathologists, features consistent with asbestosis grade 1 (AG1) include findings of bilateral pleural plaques, high concentrations of asbestos bodies (ABs) in digested lung tissue, and a history of occupational risk. Similar changes without evidence of ABs on histologic section and referred to as small airway lesions (SALs) present a less well-correlated association. In this study, SALs showed significant differences when compared with the features observed in subjects without possible asbestos-related pulmonary fibrotic changes. Minimal bronchioloalveolar fibrotic changes with concomitant presence of ABs can be considered a mild pneumoconiotic lesion (AG1), and SALs may be regarded as an additional indicator of asbestos exposure. PMID- 2914699 TI - Familial mesothelioma: a report of two families. AB - Five reports of familial mesothelioma in which mesotheliomas occurred in two or more family members have been recorded in the medical literature. In this report, we describe two examples of familial mesothelioma. In one family, three brothers who worked in the asbestos insulation industry developed mesothelioma. In the second family, the father, who was occupationally exposed to asbestos, died from a tubulopapillary peritoneal mesothelioma 11 years before his son died from an identical histologic type of peritoneal mesothelioma. Our report, as with those previously recorded, suggests that genetic factors may be important in the genesis of some mesotheliomas. PMID- 2914700 TI - Immunohistochemical study of cytochrome P-45017 alpha in human adrenocortical disorders. AB - Cytochrome P-450 specific for steroid 17 alpha-hydroxylation (P-45017 alpha) was immunolocalized in normal and hyperfunctioning adrenal glands of pigs, bovines, and humans, using a specific IgG fraction raised against the enzyme. P-45017 alpha was present in the zona fasciculata (ZF) and zona reticularis (ZR), but not in the zona glomerulosa (ZG), in pig, bovine, and human adrenal glands. In the adrenal glands of patients with Cushing's disease, the positive immunoreactivity to P-45017 alpha was intense in ZF and ZR, particularly in cortical micronodules, corresponding to the sites of active steroidogenesis. Cells of hyperplastic ZG and outer ZF in the adrenal glands of idiopathic hyperaldosteronism were negative for P-45017 alpha. In aldosteronoma, positive immunoreactivity was observed in some tumor cells, which is consistent with cortisol production and its responsiveness to ACTH in aldosteronoma. In the attached adrenal glands of aldosteronoma, the immunoreactive P-45017 alpha was clearly present in the inner ZF and ZR, suggesting persistent androgen production. In Cushing's adenoma, the positive immunoreactivity was intense in tumor cells, and the ZR of the attached adrenal glands was weakly immunoreactive. PMID- 2914701 TI - Occupational status variations in disagreements on the diagnosis of cause of death. AB - Studies of occupational status-related risk factors in specific-cause mortality assume that the proportions of disagreements concerning the diagnoses of the cause of death do not vary between different statuses. This assumption was verified by the addition of data concerning the occupation of the decreased (collected at death registration) to a data set comparing the clinicians' and the pathologists' diagnoses at autopsy of the cause of death. It was found that clinicians and pathologists were least likely to agree on the diagnoses of the cause of death of non-manual workers and were most likely to agree on the diagnosis of the cause of death of skilled manual workers. These occupational status differences in diagnostic disagreements reached levels of statistical significance in the neoplasm chapter of the International Classification of Diseases. Artefactual and clinical reasons for these occupational status differences are discussed. PMID- 2914702 TI - Invasive fibrous tumor of the tracheobronchial tree: clinical and pathologic study of seven cases. AB - We describe seven cases of invasive fibrous tumors of the trachea and major bronchi with distinctive histologies and patterns of growth. The tumors are composed of proliferating fibroblasts and have moderate nuclear pleomorphism and low mitotic activity. The tumors bear some resemblance to inflammatory pseudotumor of the lung, fibrous histiocytoma, and fibromatosis, but differ from each of these entities. The tumors are neoplastic and invade down to or between plates of cartilage. Because of their proximal location, these tumors are usually amenable to sleeve resection. Recurrence is possible. Metastasis has not occurred. Distinction from more malignant mesenchymal tumors of the trachea and bronchus will prevent unnecessarily radical surgery. PMID- 2914703 TI - Adenocarcinoid tumor of the periampullary region: a novel duodenal neoplasm presenting as biliary tract obstruction. AB - An adenocarcinoid tumor of the duodenum, similar to those arising in the appendix, is reported. The tumor presented as a periampullary mass causing pancreaticobiliary obstruction. The microscopic features were typical of adenocarcinoid with diffuse infiltration of mucosa, submucosa, and smooth muscle by tubuloglandular structures lined by enteroendocrine and goblet cells. Signet ring cells were also present. It is desirable to distinguish adenocarcinoids from adenocarcinomas and typical carcinoids in this setting as, by analogy with appendiceal tumors, adenocarcinoids may be expected to have an intermediate prognosis. PMID- 2914704 TI - The diagnosis of asbestosis. PMID- 2914705 TI - Mapping of four translocation breakpoints within the Duchenne muscular dystrophy gene. AB - There are over 20 females with Duchenne or Becker muscular dystrophy (DMD or BMD) who have X-autosome translocations that break the X chromosome within band Xp21. Several of these translocations have been mapped with genomic probes to regions throughout the large (approximately 2000 kb) DMD gene. In this report, a cDNA clone from the 5' end of the gene was used to further map the breakpoints in four X-autosome translocations. A t(X;21) translocation in a patient with BMD and a t(X;1) translocation in a patient with DMD were found to break within a large 110 kb intron between exons 7 and 8. Two other DMD translocations, t(X;5) and t(X;11), were found to break between the first and the second exon of the gene within a presumably large intron (greater than 100 kb). These results demonstrate that all four translocations have disrupted the DMD gene and make it possible to clone and sequence the breakpoints. This will in turn determine whether these translocations occur by chance in these large introns or whether there are sequences that predispose to translocations. PMID- 2914706 TI - Twenty-eight loci form a continuous linkage map of markers for human chromosome 1. AB - We have used a combination of 30 serological, protein electromorphic, and DNA markers defining 28 loci to construct a linkage map of chromosome 1. These markers form a continuous linkage group of 320 cM in males and 608 cM in females; female genetic distances were on average twofold higher than those of males across the map. Among the DNA markers are 10 highly polymorphic markers reflecting loci that contain a variable number of tandem repeats, well distributed over the length of the chromosome, that will be highly efficient anchor points for application of this map to studies of human genetic disease. PMID- 2914707 TI - A 1.5-megabase restriction map surrounding MYC does not include the translocation breakpoint in familial renal cell carcinoma. AB - A constitutional translocation t(3;8)(p14.2;q24.1) segregates concordantly with a familial form of renal cell carcinoma (RCC). This translocation moves the MYC oncogene, located at 8q24.1, onto the short arm of chromosome 3. Chromosome rearrangements that break in or near MYC can result in altered expression of this gene and are thought to be a primary change leading to the transformed phenotype in certain neoplastic diseases, particularly Burkitt lymphoma. Possible rearrangements of this gene in familial RCC have so far not been detected using standard Southern blot analysis. We used pulsed field gel (PFG) analysis to construct a restriction map that covers a 1500-kb region surrounding MYC, including over 1000 kb to the 5' and 550 kb to the 3' side of this gene. The 5' end of MYC contains a cluster of cleavage sites for rare-cutting restriction endonucleases, indicating the presence of an HTF island. PFG analysis of DNA containing the t(3;8) rearrangement shows that the breakpoint is not located in the mapped region, making it unlikely that MYC is involved in this form of renal cell carcinoma. The map should facilitate study of other chromosome 8 rearrangements thought to break near MYC. PMID- 2914708 TI - Physical fine mapping of the choroideremia locus using Xq21 deletions associated with complex syndromes. AB - Characterization of several male-viable deletions and duplications with 20 random DNA probes has enabled us to subdivide the Xq21 region into seven discernible intervals. Almost all of the deletions spanning part of Xq21 are associated with choroideremia and mental retardation, with deafness being another common feature. The gene locus for choroideremia was assigned to interval 3 spanning the loci DXS95, DXS165, and DXS233. Genes for X-linked deafness and mental retardation were tentatively assigned to interval 2. Deletions of intervals 4 through 7 were not associated with any clinical abnormality. We have constructed a preliminary long-range restriction map of intervals 2 and 3 using field-inversion gel electrophoresis. The DXS232, DXS121, and DXS233 loci are located on the same SfiI fragment, whereas the DXS165 and DXS95 loci could not be linked to this cluster using SfiI and SalI. PMID- 2914709 TI - The human glucocerebrosidase gene and pseudogene: structure and evolution. AB - We report the sequence of the entire human gene encoding beta-glucocerebrosidase and that of the associated pseudogene. The gene contains 11 exons extending from base pair 355 to base pair 7232 in the overall sequence. The gene promoter contains TATA- and CAT-like boxes upstream of the major 5' end of the glucocerebrosidase RNA. The two TATA boxes lie between nucleotides (-23)-(-27) and (-33)-(-39) and the two possible CAT boxes reside between nucleotides (-90)-( 94) and (-96)-(-99) in relation to the major 5' end of the mRNA. The functionality of the promoter region was monitored by coupling it to the bacterial gene coding for chloramphenicol acetyltransferase (CAT) and assaying the expression of the enzyme in cells transfected with this vector. The glucocerebrosidase promoter not only directs synthesis of the bacterial enzyme but also exhibits the same pattern of tissue-specific expression as that of the endogenous gene. An apparently tightly linked pseudogene is approximately 96% homologous to the functional gene. However, introns 2, 4, 6, and 7 have large "deletions" consisting of Alu sequences 313, 626, 320, and 277 bp in length, respectively. It is entirely possible that the ancestral gene lacks these sequences and that they have been inserted into the introns of the functioning gene. There is also a 55-bp deletion from a part of exon 9 flanked by a short inverted repeat. The sequence data should facilitate development of methods for diagnosis of Gaucher disease at the molecular level. PMID- 2914710 TI - Localization of nucleotide sequence which determines Mongoloid subtype of HLA B13. PMID- 2914711 TI - Nucleotide sequence of a rat class I cDNA clone. PMID- 2914712 TI - HLA-DP types of homozygous typing cells: DPw3 found in three Dw19 HTC. PMID- 2914714 TI - Percutaneous transhepatic cholecystoscopy and biliary endoscopic lithotripsy. AB - We have been developing procedures for percutaneous transhepatic cholecystoscopy (PTCCS) through the sinus tract of percutaneous transhepatic cholecystostomy since 1981, and have used this method on 67 patients with gall bladder diseases. We also performed biliary endoscopic lithotripsy with PTCCS and percutaneous transhepatic cholangioscopy (PTCS) using a Nd-YAG laser or electrohydraulic shock wave lithotripter to non-operatively treat 83 patients with cholangiolithiasis, 11 with cholecystolithiasis, and four with cholecysto-choledocholithiasis. The present paper reports the PTCCS procedures and their usefulness for the precise diagnosis of early carcinoma of the gall bladder, and the usefulness and safety of biliary endoscopic lithotripsy techniques. PMID- 2914715 TI - Duodenoscopic sphincterotomy in a northern Indian hospital. AB - In a 36-month period, 154 duodenoscopic sphincterotomies (DS) were performed on 120 patients in a Northern Indian hospital. The major indication for DS was choledocholithiasis (95.8%), the rest being done for indications like papillary stenosis, periampullary carcinoma and the sump syndrome. Seven patients (5.8%) had significant associated medical illnesses. An adequate sphincterotomy was achieved in 91.6% of patients, with successful stone extraction in 95.3% of them. Overall clearance of the common bile duct (CBD) was thus achieved in 87.5% of the patients subjected to DS. Two patients (1.7%) died after undergoing DS, and six (5%) experienced early complications that necessitated emergency operation in two of them (1.7%). DS appears to be the treatment of choice for the management of choledocholithiasis in the postcholecystectomy patient as well as in the patient with gallbladder in situ who has cholangitis or jaundice or associated medical illness that may constitute a high risk for surgery. PMID- 2914713 TI - Three new class I HLA alleles: structure of mRNAs and alternative mechanisms of processing. AB - Sixteen HLA class I clones have been isolated from a SV40-transformed human fibroblast line (GM637) cDNA library. The clones, characterized by hybridization to ABC locus-specific probes and sequence analysis, correspond to transcripts from four different class I genes: A2, A10, Cw4, and Cw6 (or Cw7), as implied by cell typing. Only the A2 sequence was known. The nucleotide and deduced amino acid sequence of the new alleles are reported here, and their structural features are discussed. Two independent cDNAs of A2 specificity display an unusual polyadenylation site located 100 bp upstream from the canonical one. Moreover, two cDNAs pertaining to the same C allele display two alternative mechanisms of splicing, which cause either presence or absence in mature transcripts of the transmembrane exon 5 sequence. Transcripts missing this region are predicted to synthesize a nonmembrane-bound, secreted antigen. A soluble protein, specifically reacting with class I-specific HLA antibodies, is found in the supernatant of the GM637 cells. The significance of HLA class I transcripts generated by differential processing is discussed. PMID- 2914716 TI - Lectin binding in colorectal mucosa. AB - Lectin binding of goblet cell mucin in human colonic mucosa was studied in patients with irritable bowel syndrome, colorectal malignancy and ulcerative colitis using plant lectins, Dolichos biflorus agglutinin (DBA) and peanut agglutinin (PNA). Normal colonic mucosa demonstrated a strong binding with DBA (100%) but did not bind to PNA at all. Colonic carcinomas showed strong PNA binding (7 of 15 biopsies) while DBA binding was absent in 14 of 15 biopsies. The transitional mucosa showed reduced or absent DBA binding in 6 and positive PNA binding in 2 of 15 biopsies. During the active phase of ulcerative colitis, there was a loss of DBA binding in 10 of 15 biopsies, which was restored during remission in all. One biopsy with severe dysplasia showed PNA binding. It is concluded that normal colorectal mucosa binds DBA strongly but not PNA. Malignant tissue and transitional mucosa reveal PNA binding often, with decreased DBA binding. In ulcerative colitis DBA binding decreases during phases of activity. PMID- 2914717 TI - Effect of phenylbutazone on acute hemorrhagic pancreatitis in dogs. AB - Experiments were conducted on 24 mongrel dogs to study the effect of phenylbutazone on acute experimental pancreatitis. Necrotico-hemorrhagic pancreatitis was produced by local infiltration of autologous bile. The severity of pancreatitis was assessed by biochemical estimation and histopathological examination. Pretreatment with phenylbutazone reduced the severity of pancreatitis, both biochemically and histologically (total score 6.0 +/- 1.52 in the test group vs 8.33 +/- 1.80 in the control group; p less than 0.01). PMID- 2914718 TI - Comparison of serum bile acids with standard liver function tests in the diagnosis of liver disease. AB - Postprandial sera of seventy patients with liver disease (hepatitis 30, cirrhosis 19, liver cancer 21) were analysed for total serum bile acids. The mean values observed in hepatitis (169.0 mumol/L), cirrhosis (112.15) and liver cancer (86.44) were significantly higher (p less than 0.001) than in normal (19.45). The frequency of abnormal bile acids was greater than that of the standard liver function tests except for alkaline phosphatase in liver cancer. PMID- 2914719 TI - Tube esophagogram: a better radiological technique for evaluation of esophageal diseases. AB - Forty-six patients with suspected esophageal disease were studied by tube esophagography. This was performed by positioning a rubber tube in the proximal esophagus, followed by swallowing of high density barium suspension and insufflation of air through the tube. Comparison in 20 cases showed superiority of tube study over conventional double contrast barium, with alteration in diagnosis in six cases and additional information in 14 cases. Tube esophagogram is a safe, simple and valuable adjunctive technique leading to accurate and definitive radiological diagnosis of esophageal disease. PMID- 2914720 TI - Saying Si to SI. PMID- 2914721 TI - A family with Peutz-Jeghers syndrome. AB - Three generations of a family with Peutz-Jeghers syndrome are described. The family chart is detailed. PMID- 2914722 TI - Hepatopetal flow in Budd-Chiari syndrome. PMID- 2914723 TI - Retained common bile duct stones: chemolysis with methyl-tert-butyl-ether. PMID- 2914724 TI - Jaundice due to albendazole. PMID- 2914725 TI - Omental tuberculosis causing acute intestinal obstruction. PMID- 2914726 TI - Percutaneous transhepatic endoscopic access to the biliary system. PMID- 2914727 TI - Role of immune serum globulin in post transfusion virus B infection. AB - Fifty four blood recipients were administered prophylactic immune serum globulin (31) or hepatitis B immune globulin (23) and followed up for six months. None of the patients developed either acute hepatitis B or HBsAg carrier state. However, 7 (14%) had anicteric self limiting non-B post-transfusion hepatitis. Twenty (40%) of the blood recipients developed anti-HBs during the follow up period suggesting either HBV exposure by subdetectable levels of HBsAg present either in blood or immunoglobulin preparation or due to passive transfer by administration of immunoglobulins. PMID- 2914728 TI - Speciation of viridans streptococci & their significance in human infections. AB - Sixty strains of viridans streptococci recovered, from various infections, encountered in a large referral Hospital in Tamil Nadu (south India) from December 1983 to May 1985 were characterised by conventional tests. Of these, 57 (95%) belonged to four species viz., Sanguis II, Mitis, Intermedius and Constellatus. Of the 40 strains that were assessed for their clinical significance, 23 (57.5%) were found to be either significant or of suggestive significance. The study suggested viridans streptococci are not particularly virulent pathogens. But local/systemic factors were found to predispose the subjects to this infection. PMID- 2914729 TI - Ischaemic mouse thigh model for evaluation of pathogenicity of non-clostridial anaerobes. AB - A mouse thigh model has been devised in which the growing culture of non clostridial anaerobe in the ischaemic tissue produces inflammatory swelling and death. The swelling of the right thigh served as an index of pathogenicity of the test strain in comparison to the negatively reacting left thigh which received injection of the control strain of Bifidobacterium infantis. Actinomyces naeslundii exceptionally caused death in all animals within 24 h. Mortality and thigh swelling were pronounced (greater than 75%) in case of Fusobacterium gonidiaformans and Propionibacterium acnes but less (less than 50%) in Acidaminococcus fermentans. High (less than 75%) rate of thigh swelling was also encountered in case of Bacteroides oralis, Bacteroides corrodens, Fusobacterium necrophorum, Fusobacterium prausnitzii, Fusobacterium plauti, Peptococcus prevotii, Streptococcus intermedius, Eubacterium lentum and Propionibacterium freudenreichii ss. shermanii. PMID- 2914730 TI - Phagocytic function of monocytes in murine model of Echinococcus granulosus of human origin. AB - Phagocytic function of monocytes was studied in E. granulosus infected Swiss albino mice, with haemolysin coated sheep erythrocytes, Staphylococcus aureus, latex particles and- Echinococcus antigen coated latex particles. No significant difference in percentage phagocytic activity was observed in mice in the early stages of infection when compared to non-infected controls (P greater than 0.05). However, in the later stages of infection, increase in the phagocytic activity was noticed. The activity was more prominent against latex particles coated with Echinococcus antigen (P less than 0.001). Although the significance of these responses is not clear, this study showed an intact inflammatory response with certain degree of specificity. PMID- 2914731 TI - Effect of permethrin impregnated bednets in reducing population of malaria vector Anopheles culicifacies in a tribal village of Orissa state (India). AB - The role of permethrin impregnated bednets at the application rate of 0.5 g (ai)/m2 in reducing A. culicifacies population in a tribal village of Orissa, highly endemic for Plasmodium falciparum was studied. The per man-hour density was significantly reduced in the Kenduguda village for about three months where impregnated bednets were supplied to the villagers, while in the control village Deulaguda where unimpregnated nets were supplied, vector density remained high during the study period. Bioassay carried out on the treated nets showed that there was 100 per cent mortality in A. culicifacies for over three months with the unwashed nets as well as with bednets washed once or twice. PMID- 2914732 TI - Mechanical properties of carotid arteries from DOCA hypertensive swine. AB - Carotid arteries from control and deoxycorticosterone acetate (DOCA) hypertensive swine were examined for alterations in structure and in contractile properties. Vessels were excised 7 weeks after subcutaneous implantation of the steroid and subsequent elevation in mean arterial pressure from 102 to 133 mm Hg. The carotid media was 1.8 times thicker in arteries from hypertensive animals than in arteries from control animals. This enlargement was associated with an increase in muscle mass, as the fraction of the media composed of smooth muscle cells remained unchanged. Maximal active stress induced by several agonists normalized for cell cross-sectional area was unaltered. No change was observed in sensitivity or maximal response to norepinephrine, histamine, or KCl depolarization. Isotonic shortening rates were also comparable, as was the time course of shortening velocity to a constant afterload during tonic contractions. It is concluded that an enlargement of the carotid media develops in this model of hypertension. However, this response is not associated with detectable alterations in contractile system function. PMID- 2914733 TI - Baroreceptor influences on oxytocin and vasopressin secretion. AB - The objective of these studies was to investigate the role of arterial baroreceptors in the control of neurohypophyseal secretion. The effect of sinoaortic denervation on basal and osmotic-induced release of oxytocin and vasopressin and on blood pressure was determined. Hypertonic or isotonic saline was infused intravenously into sham-operated or denervated rats 3 days after surgery. Plasma oxytocin and vasopressin were measured at 5 and 15 minutes after the infusion. The control levels of oxytocin were increased in the denervated rats, but vasopressin levels were not significantly altered. The vasopressin and oxytocin responses to hypertonic saline were greater after baroreceptor denervation. Plasma oxytocin was increased from 4.7 +/- 0.9 to 72.2 +/- 8.7 pg/ml in the denervated rats and from 1.8 +/- 0.3 to 39.9 +/- 6.7 pg/ml in the sham operated control group at 5 minutes after the infusion (p less than 0.01). The plasma vasopressin response to hypertonic saline was 7.1 +/- 0.6 pg/ml in the sham-operated versus 11.1 +/- 1.6 pg/ml in the denervated rats (p less than 0.05). There was no difference between sham-operated and denervated rats in the effect of hypertonic saline on plasma sodium and hematocrit. Mean arterial blood pressure was increased after sinoaortic denervation (116.3 +/- 4.2 mm Hg in the sham-operated vs. 138.2 +/- 8.3 mm Hg in the denervated rats, p less than 0.05); however, there was no difference in the pressor response to hypertonic saline. These results show that the baroreceptor system influences the secretion of both oxytocin and vasopressin, with effects on basal secretion as well as the response to an osmotic stimulus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2914734 TI - Differential effect of dietary salt on renal growth in Dahl salt-sensitive and salt-resistant rats. AB - A high salt diet has been shown to increase renal mass of intact rats, although the mechanism by which this occurs has not been investigated. We used Dahl rats that are sensitive (DS) or resistant (DR) to the hypertensinogenic effect of salt to examine changes in renal size and composition caused by a high salt diet. Renal index, deoxyribonucleic acid (DNA), protein, water content, protein/DNA ratio, and cell number and size were measured in age-matched DR and DS on a high salt diet for 7, 14, or 28 days. The results were compared with those obtained from respective rats on a low salt diet. High salt diet elevated renal index and protein in DR and DS rats at each time point. After 7 days of a high salt diet, DNA increased in DS only. Protein/DNA ratio was progressively decreased by a high salt diet in DS and remained unchanged in DR rats. Cell number was increased 35% in DS versus only 13% in DR rats at 4 weeks. Cell size decreased 24% in DS and only 11% in DR rats. These results indicate that renal growth due to hyperplasia accompanies ingestion of a high salt diet in both DR and DS rats, but the rate of growth and the mechanism through which it occurs differ between strains. This difference may be important in delineating salt sensitivity and future development of hypertension. PMID- 2914735 TI - Hemodynamics and microcirculatory alterations in reduced renal mass hypertension. AB - The objectives of this study were to determine the hemodynamic and microcirculatory changes that occur during reduced renal mass hypertension in rats. In conscious animals with 75% reduction of total renal mass, mean arterial pressure was initially (4-8 hours) elevated by 15-20 mm Hg during intravenous infusion with isonatremic (145.4 mM) NaCl. Cardiac index was elevated by 15-20%, and total peripheral resistance index was normal or reduced. Cardiac index subsequently returned toward normal, but mean arterial pressure remained elevated (20-40 mm Hg), presumably because of an elevated total peripheral resistance. Cremasteric arterioles were actively constricted (35-50%) in rats with short-term (36 hours), but not chronic (5-6 weeks) reduced renal mass hypertension. Total microvessel density was approximately 15% lower in maximally dilated cremaster muscles of chronically hypertensive rats versus sham-operated controls, which suggests that arterioles are lost during sustained reduced renal mass hypertension. Arteriolar constriction in response to increased superfusate PO2 (0% to 5% O2) was 2-4 times greater in rats with both short-term and chronic reduced renal mass hypertension than in normotensive controls, which suggests that oxygen-dependent autoregulatory mechanisms are altered. The hemodynamic and microcirculatory alterations observed in these experiments suggest that classic short-term autoregulatory mechanisms and an enhanced response of arterioles to increased oxygen availability contribute to the elevated total peripheral resistance in short-term reduced renal mass hypertension, whereas structural changes and altered vascular oxygen responses contribute to an elevated microvascular resistance in chronic reduced renal mass hypertension. PMID- 2914736 TI - Mixture analysis of erythrocyte lithium-sodium countertransport and blood pressure. AB - This study employs multivariate normal mixture analysis, a technique for identifying discrete subgroups within populations, to examine the relation of erythrocyte lithium-sodium (RBC Li+-Na+) countertransport and blood pressure in a group of 474 healthy adults. After adjusting for effects of age, gender, race, height, and weight, univariate mixture analysis of the distribution of mean arterial blood pressure (MAP) revealed the presence of only one group, whereas the distribution of RBC Li+-Na+ countertransport values was composed of a mixture of two groups (p less than 0.00005). When bivariate mixture analysis was applied to the combined distribution of MAP and RBC Li+-Na+ countertransport, two commingled subgroups were identified (p less than 0.00005). The smaller group (19%) had significantly higher values for both MAP (108.7 +/- 16.7 mm Hg, mean +/ SD) and RBC Li+-Na+ countertransport (0.455 +/- 0.147 mmol Li+/l cells.hr) than the larger (81%) group (MAP 93.3 +/- 12.2 mm Hg, RBC Li+-Na+ countertransport 0.247 +/- 0.080 mmol Li+/l cells.hr, p less than 0.0001 for both differences). The relation of MAP to RBC Li+-Na+ countertransport was distinctly different in these two subgroups. In the larger group, we found a weak positive (r = 0.21, p less than 0.0001) correlation for unadjusted values, which was not significant after adjustment. The smaller group, with higher levels of MAP and RBC Li+-Na+ countertransport, showed significant negative correlations for both unadjusted (r = -0.28, p less than 0.008) and adjusted (r = -0.41, p less than 0.0001) values. PMID- 2914737 TI - Forearm blood flow responses of offspring of hypertensives to an extended stress task. AB - The forearm blood flow and other cardiovascular responses of 10 healthy young men with a parental history of hypertension to an extended laboratory stressor were compared with the responses of 10 age-matched men with normotensive parents. To eliminate the effects of the anticipation of stress on baseline measures, all subjects participated in a separate 1-hour counterbalanced baseline session in which no stress was presented. There were no significant differences between the two groups in resting blood pressure, heart rate, blood volume pulse, forearm blood flow and vascular resistance, and self-report anxiety, although offspring of hypertensive parents exhibited marginally greater (p = 0.08) forearm blood flow at rest. During the stress session, subjects played video games for 1 hour and avoided mild electric shocks depending on performance. Offspring of hypertensive parents exhibited significantly greater heart rate (+19 +/- 6 vs. +3 +/- 2%), forearm blood flow (+52 +/- 14 vs. +9 +/- 4%), and self-report anxiety (+25 +/- 6 vs. +9 +/- 3%) responses to the task. There were no significant group differences in blood pressure response to the task. Significant positive correlations between forearm blood flow and heart rate responses to the task were observed. These findings extend earlier results that suggested healthy young offspring of hypertensive and normotensive parents may exhibit different patterns of hemodynamic response to stress in the absence of differences in resting blood pressure or blood pressure responsiveness to stress. PMID- 2914738 TI - Molecular evidence of genetic heterogeneity in Wistar-Kyoto rats: implications for research with the spontaneously hypertensive rat. AB - Spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto ("WKY") rats are frequently employed in experimental studies of hypertension. Although both SHR and WKY rat strains have been presumed to be fully inbred, recent studies have revealed important biologic variability in WKY rats from different commercial sources. Genealogic evidence suggests that, in the United States, breeding stocks of WKY rats may have been distributed to major commercial suppliers as early as the F10 generation. To test the hypothesis that commercially available WKY rats are genetically heterogeneous, we performed deoxyribonucleic acid (DNA) "fingerprint" analysis on genomic DNA of WKY rats from two of the largest vendors in the United States, Taconic Farms and Charles River Laboratories. We found molecular evidence of genetic variability not only among WKY rats from two different breeding facilities, but also among WKY rats within a single breeding facility (Taconic Farms). Although some studies have suggested the possibility of biologic variability in SHR from different sources, preliminary studies have not revealed molecular evidence of genetic heterogeneity in SHR from these vendors. In demonstrating genetic variability in WKY rats from different sources, the current study provides compelling evidence that rats designated WKY do not constitute an inbred strain. Accordingly, the results of studies in which SHR and WKY rats are compared might vary because of genetic heterogeneity in "the WKY rat control strain." PMID- 2914739 TI - Interatrial conduction block with retrograde activation of the left atrium and paroxysmal supraventricular tachyarrhythmias: influence of preventive antiarrhythmic treatment. AB - Patients with advanced interatrial conduction block with retrograde activation to the left atrium present a high incidence of supraventricular tachyarrhythmias. We report the value of preventive antiarrhythmic treatment in these patients. PMID- 2914740 TI - Cardiac tamponade as the initial presentation of malignancy. AB - We describe a series of five patients who had cardiac tamponade at the time of initial presentation as a result of extracardiac malignancy. Three cases had adenocarcinoma and two had squamous cell carcinoma. The diagnosis of bronchogenic carcinoma was established after appropriate investigations in three cases. One patient possibly had a primary malignancy of the gastro-intestinal tract. The relevant literature is reviewed. PMID- 2914741 TI - Electrophysiologic evaluation of intravenous nicardipine in man. AB - The acute electrophysiological effects of intravenous nicardipine (0.014 mg/kg per min for 5 minutes) were studied in 12 subjects with estimated normal sinus node functions and atrioventricular conduction parameters. The most important effects were sinus cycle length shortening, increase of corrected sinus node recovery time and reduction of effective and functional refractory period of the atrioventricular node. Sinuatrial conduction time, atrial refractory periods, intranodal conduction, bundle branch refractoriness and ventricular refractoriness were unchanged. Systolic and diastolic blood pressure was reduced. The clinical implications of these properties of the drug are discussed and compared with those of verapamil, diltiazem and nifedipine. PMID- 2914742 TI - The atrial pacemaker: retrospective analysis of complications and life expectancy in patients with sinus node dysfunction. AB - The safety of atrial pacemakers is still a remaining cause of controversy. Since 1972, we have implanted 111 atrial pacemakers and we were able to follow-up 100 patients continuously. Mean follow-up time was 47 +/- 36 months (maximum 154 months) with a total population time of 391 patient years. Over a period of 10 years, the cumulative incidence of complete atrioventricular block was 4% (2 patients). The cumulative incidence of atrial fibrillation was 11% (5 patients). Lead-related complications were strongly dependent on the type of the lead and the mode of fixation. The cumulative incidence of all lead-related problems was 19% over a period of 5 years and 33% over a period of 10 years. The cumulative survival rate was 85% for 5 years and 61% for 10 years. These survival rates were not different from the survival rate of a matched cohort of the normal population. We conclude that atrial pacing could be done in patients with sick sinus syndrome. The risk of developing a complete atrioventricular block seems to be rather low. The main problem of the atrial pacemaker is the fixation of the lead which could be reduced by using screw-in-type leads. PMID- 2914743 TI - Assessment of right ventricular function in acute inferior myocardial infarction using 133-xenon imaging. AB - The detection of right ventricular dysfunction in acute inferior myocardial infarction is important because of its potentially serious consequences which may be remediable with the appropriate therapeutic manoeuvres. A technique has been developed to assess right ventricular function using 133-xenon. This technique was applied to 26 patients who had sustained an acute inferior myocardial infarction. Right ventricular ejection fractions ranged from 7-54%, mean 30 +/- 11%, which was significantly lower than values obtained from normal volunteers (n = 21), mean 43 +/- 5%, and patients with arteriographically proven coronary artery disease without previous myocardial infarction (n = 12), mean 39 +/- 9%, P less than 0.001, and P less than 0.001, respectively. In the patients with acute inferior myocardial infarction 18 patients (69%) had evidence of right ventricular dysfunction (right ventricular ejection fraction less than 35%). 13/26 patients (50%) had clinical evidence of right ventricular dysfunction with a mean right ventricular ejection fraction 26 +/- 11% (range 7-54%) which was significantly lower than the patients without evidence of right ventricular dysfunction, mean 35 +/- 9% (range 16-49%), P less than 0.001. The clinical signs had a sensitivity of 72% (13/18), a specificity of 87.5% (7/8) and a predictive accuracy of 76% (20/26) when compared to the imaging data. IN CONCLUSION: (1) gated 133-xenon imaging provides a method for assessing right ventricular function in the setting of acute myocardial infarction; (2) a wide spectrum of right ventricular dysfunction occurs following inferior myocardial infarction which may not manifest itself clinically. PMID- 2914744 TI - Evaluation of myocardial thallium tomography in patients with chest pain. AB - Thirty-seven patients with chest pain have been studied by exercise thallium tomography and coronary arteriography to assess the accuracy of thallium tomography in the identification of patients with coronary artery disease and to evaluate whether knowledge of clinical data improves this accuracy. Thallium tomography was also used to identify which coronary arteries were stenosed. Thallium tomography when compared with coronary arteriography has a sensitivity of 97%, a specificity of 75%, and an overall accuracy of 92% for the detection of coronary artery disease. When clinical information was made available, these results improved to a sensitivity of 100%, a specificity of 75%, and an overall accuracy of 95%. In the identification of which coronary arteries were stenosed, thallium tomography had a sensitivity of 85%, a specificity of 89%, and an overall accuracy of 86%. These results show that exercise thallium tomography can be an accurate non-invasive screening test in patients with chest pain thought to be angina. PMID- 2914745 TI - Surgical pathology of disease of the mitral valve, with special reference to lesions promoting valvar incompetence. AB - A consecutive series of 459 mitral valves, which had been surgically excised over a 6-year period, were evaluated by means of macroscopic and histologic study. Of the valves, 379 specimens showed evidence of rheumatic disease (82.6%), 51 were floppy (11.1%), while 29 (6.3%) belonged to a heterogeneous group. The last included cases of ischemic disease (2.4%), infective endocarditis (2.4%), congenital dysplasia (0.9%), rheumatoid arthritis (0.4%), and primary dystrophic calcification (0.2%). Eighty-seven patients had had pure mitral incompetence. Among these, floppiness of the leaflets was the major indication for valvar replacement (58.6%), followed by rheumatic disease (12.7%), ischaemic incompetence (12.7%), and infective endocarditis (11.5%). Particular attention was paid to the clinical-pathological profile of patients with floppy valves as the cause of severe incompetence. This confirmed the prevalence of male patients and the frequent incidence of complications, particularly rupture of tendinous cords (54.9%). A striking difference was also found between the mean age of those patients with and without Marfan's disease (15.3 vs. 53.9 years, P less than 0.001). Although mitral incompetence in the presence of a floppy valve could simply be due to deformity of the leaflets, elongation of the cords and dilatation of the atrioventricular junction, in over half of the cases the precipitating event leading to surgery was rupture of tendinous cords. PMID- 2914746 TI - Facial and immunological anomalies associated with tetralogy of Fallot. AB - Dysmorphic facial features were present in 9 of 31 children with tetralogy of Fallot anatomy (29%). These anomalies included hypertelorism, low-set ears, small mouth, short philtrum, and micrognathia. Ten children had pulmonary atresia, 13 (42%) had a right aortic arch, and 13 had extracardiac congenital anomalies. There were 16 children in the series (52%) who had hospital admissions for important or recurrent infections, and 18 who had immune deficiency: low levels of T lymphocytes were found in 9, low levels of complement in 8, and low immunoglobulins in 3. Embryologically, the cardiac outflow tracts, the aortic arch, the face, and the thymus develop at the same time, and all receive migrating cells from the neural crest. Teratogenic factors possibly produce this constellation of anomalies, which is in the spectrum of the Di George syndrome (third and fourth pharyngeal pouch syndrome). It is of importance for the management of such children, that their immune deficiency be recognized and treated appropriately. PMID- 2914747 TI - Double mitral valve orifice and primary pulmonary hypertension. AB - We describe the combination of double mitral valve orifice of the complete bridge variety, or type 1, and primary pulmonary hypertension, a previously unreported association. The complete diagnosis was established by two-dimensional Doppler echocardiography and the hemodynamics corroborated by cardiac catheterization. PMID- 2914748 TI - Right-sided heart with mirror-image atrial arrangement, complete transposition, ventricular septal defect and subpulmonary stenosis. AB - An infant is described with complete transposition in the setting of a right sided heart, and mirror-image atrial arrangement. A ventricular septal defect and subpulmonary stenosis were also present. We discuss the anatomic features of this patient, undescribed prior to this case, and their implications for surgical repair. PMID- 2914749 TI - Electrocardiographic correlates of hyperglycemia in acute myocardial infarction. AB - Clinical, biochemical and electrocardiographic parameters were studied in 10 patients with uncomplicated acute myocardial infarction with hyperglycemia (but normal glycosylated hemoglobin), and 15 age- and sex-matched patients with uncomplicated acute myocardial infarction without hyperglycemia. The magnitude of hyperglycemia correlated with the site and extent of the infarct, the magnitude of ST-segment elevation and the levels of 17-ketosteroids in the urine. PMID- 2914750 TI - Primary cardiac amyloidosis with pathologic hip fracture secondary to bone amyloid. AB - A rare combination of primary cardiac amyloidosis and bone amyloidosis is described in a 39-year-old female. The presenting features were restrictive heart disease and a destructive bone lesion. The diagnosis was confirmed with the help of endomyocardial and bone biopsy. PMID- 2914751 TI - Degenerative changes in a retina affected with autosomal dominant retinitis pigmentosa. AB - The eyes of a 17-year-old male donor who was affected with autosomal dominant retinitis pigmentosa with variable expressivity have recently become available for study. Initial macroscopic examination of the fundus revealed bone spicules located in 180 degrees of the postequatorial fundus centered on the inferonasal quadrant. Light microscopic examination of the retina showed degeneration within each quadrant characterized by an absence of rods and cones in the equatorial areas, and the presence of photoreceptors in the more peripheral and central retina. Ultrastructural examination disclosed photoreceptors that were abnormal in all regions when compared to a control eye from a 26-year-old donor. Intact rods were restricted to the peripheral quadrants, and intact cones were identified in the fovea and far periphery. In areas of intermediate degeneration, many outer segments were either shortened and disorganized or absent. Regions of severe degeneration were characterized by the complete loss of the photoreceptors and apposition of the external limiting membrane to the retinal pigment epithelium. The density of rods and cones was found to be substantially lower than normal in all regions. In areas of relatively intact photoreceptor outer segments, we found ultrastructural evidence of recent phagocytic activity, and fluorescence microscopy revealed no unusual accumulation of lipofuscin within the pigment epithelium or subepithelial debris. The choroid and inner retina were normal throughout the eye. The normal condition of the choroid, retinal pigment epithelium, and inner retina implies that the primary disorder resides within the photoreceptor cell. PMID- 2914752 TI - Reversibility of retinal adhesion in the rabbit. AB - We have studied retinal adhesion in the rabbit using a new technique for quantifying adhesiveness by the observation of how much pigment remains adherent to the photoreceptors after separation. Previous in vitro work has shown that retinal adhesiveness falls within 3 min after enucleation, is weakened by low pH or the removal of calcium and magnesium, and is increased by cold temperature. This report shows that the effects of low pH, low calcium/magnesium and temperature are all rapidly reversible. Thus, restoring normal pH or normal calcium/magnesium will restore adhesiveness to control levels, and adhesion may be repeatedly weakened or strengthened by the adjustment of temperature or the ionic environment. The actions of pH and calcium/magnesium are in part additive, while cold temperature can maintain adhesion even in low pH or low calcium/magnesium. These findings suggest that irreversible processes such as metabolic or enzymatic decay are not primarily responsible for the loss of retinal adhesion which occurs so rapidly after enucleation or death. They also suggest that retinal adhesion is a multifactorial process. PMID- 2914753 TI - Hydrostatic pressure of the suprachoroidal space. AB - The hydrostatic pressure of the suprachoroidal space was measured in 18 cynomolgus monkey eyes by one of two methods: (1) direct cannulation, or (2) silicone sponge implantation. The intraocular pressure (IOP) and suprachoroidal pressure were monitored simultaneously with the IOP being held at various levels between 5 and 60 mm Hg. In eyes with direct cannulation, at an IOP of 15 mm Hg, the pressure in the anterior suprachoroidal (supraciliary) space was 0.8 +/- 0.2 mm Hg (n = 6, mean +/- SE) below the IOP, but the posterior suprachoroidal pressure was 3.7 +/- 0.4 mm Hg (n = 8) below the IOP. The suprachoroidal pressure in eyes with silicone sponge implant was 4.7 +/- 0.6 (n = 7) mm Hg below the IOP. A change in IOP produced a corresponding change in the supraciliary space pressure. However, the pressure difference between the anterior chamber and the posterior suprachoroidal space increased at higher IOP. This pressure differential is the driving force for uveoscleral outflow. PMID- 2914754 TI - Expression of transforming growth factor-beta in wound healing of vitamin A deficient rat corneas. AB - Transforming growth factor-beta (TGF-beta) is a multifunctional peptide that modulates cell proliferation and differentiation in many cell types and accelerates tissue repair response. In this study, expression of TGF-beta was investigated immunohistochemically in the healing of central 3 mm epithelial wounds of vitamin A-deficient (A-) rat and pair-fed controls. In control rat corneas, a positive reaction to TGF-beta was not evident during wound healing. In A- rat corneas at 4 hr post-abrasion, acute inflammatory cells showing high positivity to TGF-beta appeared in the peripheral stroma and gradually spread to the central cornea. By 24 hr, these cells accumulated and formed a pseudomembrane in the epithelial defect, which also showed an intense positivity to TGF-beta, suggesting that the peptide participates even in the acute inflammatory response. From about 16 hr post-injury, many fibroblasts revealing intense positivity to TGF-beta infiltrated the entire stroma and were part of the healing process. Reepithelialization occurred over the pseudomembrane and was completed by 48 hr. The central cornea showed remodeling of collagen structure and neovascularization. Fibroblasts containing TGF-beta were seen in the stroma, indicating that TGF-beta plays an important role in corneal wound healing. Indeed, in the absence of vitamin A, a common modulator of cell differentiation, TGF-beta may play a more important role in wound healing than in the normal state. PMID- 2914755 TI - Expression of types I and IV collagen genes in normal and in modulated corneal endothelial cells. AB - Expression of type I and type IV collagen genes was studied in normal endothelial cells and in modulated endothelial cells (formerly designated as fibroblastic corneal endothelial cells: FCEC). There appear to be distinct collagen phenotypes in these cells; normal cells produce type IV collagen as a major type, while the modulated cells produce predominantly type I collagen. The absence of type I synthesis in normal cells, and absence of type IV collagen in FCEC were confirmed by immunoblot analysis of the accumulated collagen in the cellular and medium layers in cultures of these cells. When collagen mRNAs were translated in a cell free system, the results indicate that neither type I collagen RNAs in the normal cells, nor type IV collagen RNAs in the modulated cells were translated. Using cloned cDNA probes, the relative quantities of transcripts of these collagens were determined by slot blot hybridization; normal cells, which synthesize no detectable type I collagen, were found to contain type I collagen RNAs in similar amounts as did the modulated cells, while the levels of type IV RNAs in modulated cells were as high as those in normal cells, in spite of the absence of their translational products. Northern blot analysis demonstrated that there are no distinct differences in the size of type I collagen RNAs in the normal and modulated cells. In contrast, type IV collagen RNA in the modulated cells was much smaller than the normal cells, suggesting that the alpha 1(IV) RNA is readily degraded.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2914756 TI - Effect of monocular visual loss upon stability of gaze. AB - Using the eye-coil/magnetic field method, we measured horizontal and vertical movements of both eyes in four patients with monocular loss of vision while they attempted steady, binocular fixation of a visual target. We also measured gaze stability in two normal subjects while they fixed upon a target monocularly, and in one patient with congenital, bilateral blindness. In the patients with monocular visual loss, gaze instability was greater in the blind eye, both vertically and horizontally, compared either with their seeing eye or with nonviewing eyes of control subjects. Gaze instability due to monocular blindness resulted from: (1) low-frequency, low-amplitude, bidirectional drifts that were more prominent vertically; and (2) unidirectional drifts, with nystagmus, that were more prominent in the horizontal plane. Gaze-evoked nystagmus, however, was not a feature of monocular blindness. Thus, the gaze instability of monocular blindness may reflect disruption of: (1) a monocular visual stabilization system; (2) fusional vergence mechanisms; or (3) both. In contrast, bilateral congenital blindness led to nystagmus with horizontal and vertical components and a wandering null point, indicative of an abnormal neural integrator. PMID- 2914757 TI - Analysis of spatial structure in eccentric vision. AB - The analysis of spatial structure, ie, the encoding of relative positions between pattern elements, was studied in central and eccentric vision. In a two alternative forced-choice task the observer had to discriminate between two patterns consisting of short line segments. At each trial the two patterns were flashed for 140 msec and the observer indicated whether the patterns were identical or mirror symmetric. Psychometric functions were measured by changing pattern size at each eccentricity in order to find the threshold size allowing 75% of correct responses. The scaling factor, required for discriminating between mirror symmetric and identical patterns independent of eccentricity, was found to be similar to the size-scaling proposed by Levi et al (Vision Res 25:963, 1985) for vernier acuity tasks. PMID- 2914758 TI - Optic disc cupping: prevalence findings from the WESDR. AB - Increased cupping of the optic disc is considered to be an indication of pressure related damage of the optic nerve. This paper explores the relationship of intraocular pressure and cupping in persons with diabetes mellitus, a group of people whose optic nerves may be more susceptible to the effects of intraocular pressure. Stereoscopic fundus photographs of the seven standard fields were obtained in all persons participating in the Wisconsin Epidemiologic Study of Diabetic Retinopathy at the time of the initial prevalence survey. Measurements of disc and cup diameters in the vertical and horizontal meridia were made by two trained graders. Cup-to-disc ratios were computed for both diameters of each eye and the mean of the two gradings was used. A history of glaucoma was significantly associated with larger cup-to-disc ratios at the prevalence examination. Cup-to-disc ratios were not larger in those with high IOP, nor in those who had panretinal photocoagulation. PMID- 2914759 TI - Optic disc cupping: four year follow-up from the WESDR. AB - Change in optic disc cupping was evaluated in a 4-year follow-up of a well defined cohort of people with diabetes mellitus. Cup-to-disc ratios were computed for both vertical and horizontal diameters of each eye at the baseline and 4-year follow-up examinations. Graders were masked as to the identity of participants and to the dates of the photographs. Increases of at least 0.1 between baseline and follow-up were used as clinically significant change in the ratios. None of the following factors at baseline were consistent predictors of such a change: intraocular pressure, age, duration of diabetes, hypertension or severity of diabetic retinopathy. People who developed proliferative retinopathy by the follow-up examination were not more likely to have such an increase in ratio at the follow-up. We conclude that clinically significant increases in cup-to-disc ratio cannot be consistently predicted in people with diabetes from the risk factors evaluated with the grading system used in this study. PMID- 2914760 TI - Intraocular antibody synthesis during experimental uveitis. AB - Determination of intraocular antibody synthesis against certain microorganisms is a diagnostic aid in identifying the causative agent in clinical uveitis. Little is known, however, concerning the kinetics and specificity of antibodies produced during intraocular inflammation. To investigate this subject we induced uveitis in rabbits by injecting small amounts of human serum albumin (HSA) into the vitreous. Aqueous humor and serum were taken before and after the induction of uveitis and levels of total IgG, rabbit albumin and anti-HSA-IgG were determined. The anti-HSA-IgG was quantitated using immunoaffinity purified anti-HSA-IgG as a standard. Six weeks after intravitreal HSA injection, high levels of total IgG (4.7 mg/ml) and albumin (15.4 mg/ml) were observed in the aqueous as compared to control eyes (IgG: 0.12 mg/ml; albumin: 0.48 mg/ml). Using albumin to correct for blood aqueous barrier breakdown we calculated that only 0.6% of the locally synthesized IgG was directed against intravitreally injected HSA. Two months after the intravitreal injection of HSA the main signs of the uveitis had subsided. A recurrent uveitis was subsequently induced by an intravenous HSA injection. This resulted in a marked increase of total IgG (14.3 mg/ml) and albumin (24.6 mg/ml) in the aqueous humor of the uveitis eyes. It was remarkable that the mean anti-HSA-IgG level (0.62 mg/ml) in the uveitis eyes was higher than that seen in serum (0.41 mg/ml). After this secondary uveitis, 9% of the locally synthesized antibodies were directed against HSA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2914761 TI - Cell density of human lens epithelium in women higher than in men. AB - Flat preparations of the central lens epithelium in 181 human donor eyes, 120 male, 61 female, were used to determine epithelial cell density. Donor age ranged from 13 to 91 years. A similar linear age-dependent decrease of cell density was found in both sexes. In addition, the epithelial cell density was significantly higher in females. The age-adjusted mean cell density in males was 5008.6 cells/mm2, in females 5780.6 cells/mm2. A similar sex difference had been found before in lens epithelium of human cataracts. The cause and significance of this observation are unknown. PMID- 2914762 TI - Cytochalasin D disrupts outer segment disc morphogenesis in situ in rabbit retina. AB - Exposure of rabbit retina to cytochalasin D (CD) via a single intraocular injection results in basal rod outer segment (ROS) and cone OS (COS) discs with abnormally large diameters; the overgrown OS membranes extend along either the cell outer or inner segment. Twenty-four hours after the injection, basal ROS and COS discs appear to have recovered their normal diameter, indicating the reversibility of this drug's effect. These data support both the evagination hypothesis for disc morphogenesis and the hypothesis that f-actin's role at the ROS base is to regulate the initiation of membrane evagination and disc diameter. PMID- 2914763 TI - Topical phenylephrine for mydriasis affects rabbit retinal pigment epithelial transport. AB - Rabbit retinal pigment epithelium (RPE) has an alpha-1 adrenoreceptor that substantially reduces RPE short circuit current (Isc) when stimulated. Since phenylephrine is a potent alpha adrenergic agonist frequently used to obtain pupil dilation, we examined the effect of topically applied phenylephrine for pupil dilation on RPE transport. Naive black dutch-belted rabbits received either one drop of 10% phenylephrine applied at t = 0 and t = 30 min or one drop of 1% cyclopentolate applied at t = 30 min. At t = 50 min, RPE-choroid-sclera explants from these animals were sealed in an Ussing chamber. At t = 60-70 min, 1.4 X 10( 4) M epinephrine was introduced into both sides of the Ussing chamber. The change in Isc produced by epinephrine was measured. The Isc reduction in rabbits receiving phenylephrine was 26% (+/- 5% SD, n = 6). The Isc reduction in rabbits receiving cyclopentolate was 39% (+/- 6% SD, n = 5). These values are significantly different (P less than 0.02, student two-tail t-test). These results indicate that topical phenylephrine reached the RPE in vivo and prestimulated the alpha-1 adrenoreceptors. PMID- 2914765 TI - Benefits for women. PMID- 2914764 TI - All part of being a woman? PMID- 2914766 TI - Osteoporosis--the silent epidemic. AB - Osteoporosis is a very common disorder which receives much less attention than it deserves, both from the general public and from a large section of the medical community. This article describes osteoporosis, the problems it causes and their scale, and looks at the prospects for prevention and treatment. PMID- 2914767 TI - Women's health--the feminist contribution. AB - Health visitor education and practice is seen within a feminist context with reference to the patriarchy of language, literature and academic studies. PMID- 2914769 TI - Screening: the political context. PMID- 2914768 TI - Aspects of women's health care in Finland. AB - The article is drawn from experience gained on a management study trip to Finland, and begins with a general explanation of the Finnish health care system, which is based on local government. Planning progress over the last fifty years is outlined, culminating in the present emphasis on primary care. There is a short section on family planning, followed by a description of abortion legislation and its effects on the birth rate. Antenatal care is also considered, particularly the important role of public health nurses and the lack of contact during pregnancy with the hospital staff who will attend the delivery. Finally the generous Finnish system of maternity leave is described. PMID- 2914770 TI - Well you can come in but i'm not having it. The role of the health visitor in computer-managed cervical screening. AB - Health visitors called on women who had not attended for a cervical smear test, following an invitation via a computer-managed scheme. Reasons for non-attendance were identified and the study showed that health visitors can be successful in encouraging some non-attenders to be screened. However, there are problems involved in undertaking such a role, which must be acknowledged if the health visitors's time is to be used effectively. PMID- 2914771 TI - The changing patterns of women's smoking. AB - Women's smoking habits from 1920 to 1986 are described. Nowadays, working class women and mothers on low incomes are more likely to be smokers. The attention of health visitors is drawn to the conflict these women demonstrate between health keeping and house-keeping. PMID- 2914772 TI - Women and alcohol. AB - The research for this article was carried out while the author was on ENB course 962 (Recognition and Management of Substance Abuse). It describes the increase in alcohol consumption among women, its causes and effects, how women and society perceive alcohol, and the type of help available. PMID- 2914773 TI - The nutritional approach to pre-menstrual tension. PMID- 2914774 TI - Orthopedics in greyhounds. PMID- 2914775 TI - Radiographic signs of isolated splenic torsion in dogs: eight cases (1980-1987). AB - Abdominal radiographs of 8 dogs with confirmed isolated splenic torsions were evaluated retrospectively. Radiographic signs included suboptimal abdominal detail, displacement of other abdominal organs, loss of visualization of the body of the spleen in its normal position (in the left cranial portion of the abdomen) on the ventrodorsal radiographic view, identification of the spleen in an abnormal location or shape, splenomegaly, and splenic gas. When the spleen location and shape could be identified as abnormal (3 dogs), the spleen appeared folded into a C shape in the central portion of the abdomen on the lateral radiographic view. PMID- 2914776 TI - What is your diagnosis? Lysis of the right temporal bone adjacent to the temporomandibular joint. PMID- 2914777 TI - What is your diagnosis? Ectrodactyly. PMID- 2914778 TI - Death or resurrection for bulk drugs? PMID- 2914779 TI - Addison's disease drug available to veterinarians. PMID- 2914780 TI - Use of animals in research: can we find a middle ground? PMID- 2914781 TI - Animal technician shortage--any solution? PMID- 2914782 TI - Analyses needed to link food with listeriosis. PMID- 2914783 TI - CDC identifies listeriosis risks. PMID- 2914784 TI - Can it be true? A manpower shortage? PMID- 2914785 TI - More on benefits of animal research. PMID- 2914786 TI - Veterinarians and state reciprocity requirements. PMID- 2914787 TI - ECG of the month. The sudden death of a dog with dilatative cardiomyopathy. PMID- 2914788 TI - Efficacy of cefadroxil in the treatment of bacterial dermatitis in dogs. AB - Cefadroxil was found to be an effective antibiotic for the treatment of canine bacterial pyoderma. Bacterial pyoderma was diagnosed in 30 dogs, which were treated with cefadroxil administered orally at 22 mg/kg of body weight, q 12 h, for 21 to 30 days. Dogs were reexamined at the conclusion of antibiotic treatment, and 29 were found to have good to excellent response. On the basis of this study, cefadroxil is a good choice in the treatment of canine pyoderma when cephalosporins are necessary. Efficacy, frequency of administration, cost, and veterinary approval are the major advantages. PMID- 2914790 TI - More on living within the practice income. PMID- 2914789 TI - Euthanasia of healthy pets. PMID- 2914791 TI - Radiotherapy of soft tissue sarcomas in dogs. AB - Megavoltage radiotherapy was administered to 42 dogs with soft tissue sarcoma. Acceptable local control of these aggressive tumors was achieved after one year of treatment. Control rates of 48 and 67% were obtained at doses of 45 and 50 gray (Gy), respectively. At 2 years, control rates decreased to 33% at the dose of 50 Gy. Serious complications developed in 4 of 42 dogs at doses of 40 to 50 Gy. The estimated dose with a 50% probability for causing serious complications was 54 Gy, given in 10 fractions. We believe that the large doses per fraction used in this study probably led to an increased probability for necrosis. Hemangiopericytomas seemed to be more responsive than fibrosarcomas. Only 2 of 11 recurrent tumors were controlled with surgery. Good local control was achieved with radiation alone for one year at doses with a low probability for serious complications; however, higher total radiation doses or combined modalities, such as surgery and radiation or radiation and hyperthermia, may be needed for longer term control. PMID- 2914792 TI - Avocado (Persea americana) intoxication in caged birds. AB - Avocados of 2 varieties were mashed and administered via feeding cannula to 8 canaries and 8 budgerigars. Two control budgerigars were given water via feeding cannula. Six budgerigars and 1 canary died within 24 to 47 hours after the first administration of avocado. Deaths were associated with administration of both varieties of avocado. Higher dose was associated with greater mortality. The 2 budgerigars given water were normal throughout the observation period. Results indicated that avocados are highly toxic to budgerigars and less toxic to canaries. Postmortem findings observed in some birds included subcutaneous edema in the pectoral area and hydropericardium. PMID- 2914793 TI - Branchial cyst in a dog. AB - A 7-year-old spayed German Shorthaired Pointer was determined to have a branchial cyst in the subcutaneous tissues of the cervical/facial area. Treatment had been attempted by aspiration and placement of drains, but without success; the final diagnosis was made after microscopic examination of the wall of the excised cyst. The means by which fluctuant swellings in this region may be differentiated are anatomic location and examination of full-thickness biopsy specimens of cyst walls. PMID- 2914794 TI - Clostridial myositis in a dog. AB - Myositis caused by Clostridium septicum was diagnosed in a 3-year-old Doberman Pinscher. The illness was characterized by signs of pain, swelling, and lameness of left forelimb. Despite treatment, the dog died. Necropsy revealed crepitant swelling over the entire left forelimb, thoracic and abdominal wall, and lumbosacral area. Subcutaneous edema and black, emphysematous muscles also were found. Histologically, hemorrhages, congested vessels, and degeneration and necrosis of myofibers with scattered infiltration of neutrophils were seen in the affected muscles. PMID- 2914795 TI - Struvite urolithiasis in cats. PMID- 2914796 TI - Pulmonic stenosis and right-to-left atrial shunt in three dogs. AB - Using cardiac catheterization, pulmonic stenosis and right-to-left atrial shunt were diagnosed in 3 young dogs that were evaluated because of weakness, cyanosis, and polycythemia. Injection of contrast material into the caudal vena cava or crossing the atrial septal defect with the catheter tip from the right atrium into the left atrium confirmed the diagnosis. Tetralogy of Fallot, with right-to left shunt through a ventricular septal defect, is a more common congenital malformation associated with the aforementioned clinical signs. Differentiation between the 2 defects is important, because surgical decompression of the right ventricle will lead to reduction of right atrial pressure and diminishment of the shunt. PMID- 2914798 TI - Primary vertebral hemangiosarcoma in a dog. AB - A 7-year-old spayed Cocker Spaniel was evaluated for recurrent hind limb paraplegia. Radiography and myelography revealed a compression fracture of T-9 secondary to a lytic process. Findings at necropsy and histologic and immunohistochemical examinations revealed 3 sites of hemangiosarcoma in each of the bodies of T-9 to T-11. Primary vertebral hemangiosarcoma is rare, and in this dog may have represented a multicentric occurrence or a primary neoplasm with adjacent metastatic foci. PMID- 2914797 TI - Use of danazol for treatment of corticosteroid-resistant immune-mediated thrombocytopenia in a dog. AB - A routine health screen of a 7 1/2-year-old female Beagle participating as a control in a long-term study revealed thrombocytopenia. Immune thrombocytopenia was diagnosed on the basis of regenerative bone marrow findings (high number of megakaryocytes) and evidence of antiplatelet antibodies. Treatment with prednisone at dosages up to 1 mg/kg of body weight every 12 hours resulted in limited improvement, with relapses of severe thrombocytopenia thwarting attempts to taper the corticosteroid, and was further complicated by side effects of the drug. Addition of danazol to the treatment regimen (5 mg/kg, q 12 h) resulted in remission of the thrombocytopenia within 2 weeks and permitted the dosage of prednisone to gradually be reduced and discontinued. Associated with this response was a decrease in platelet-associated IgG to values comparable with control samples. PMID- 2914799 TI - Professional dental care. PMID- 2914800 TI - Arthrodesis of metatarsophalangeal joints in a dog. AB - Chronic osteomyelitis and septic arthritis involving the 3rd and 4th metatarsophalangeal joints were diagnosed in a Doberman Pinscher. Arthrodesis of the 3rd and 4th metatarsophalangeal joints resulted in a subtle persistent gait abnormality, but limb function was preserved. Arthrodesis of metatarsophalangeal joints is an alternative to amputation, especially when main weight-bearing digits are involved. PMID- 2914801 TI - Conservative management of fractures of the mandibular condyloid process in three cats and one dog. AB - Three cats and 1 dog with fracture of the mandibular condyloid process and concomitant fracture(s) of the rostral portion of the mandible were treated successfully by wire fixation of the rostral mandibular fracture(s) and by conservative management of the mandibular condylar fracture. All animals regained satisfactory dental occlusion and normal, pain-free motion of the jaw. Fracture of the mandibular condyloid process is an infrequently diagnosed injury that usually occurs with other mandibular fractures. If satisfactory dental occlusion can be achieved by surgical stabilization of the noncondylar fractures, surgical repair of the mandibular condyloid fracture may not be necessary. PMID- 2914802 TI - Traumatic urethral avulsion at the preputial fornix in a cat. AB - A cat with pelvic fractures from being hit by a car had voided no urine in 13 hours despite iv administration of fluids. Abdominal radiography had revealed the pelvic fractures and apparently intact urinary bladder. Urine did not flow from a urethral catheter, and contrast radiography revealed the catheter to be extra urethral within the penis. Intravenous pyelography revealed intact ureters and urinary bladder; celiotomy confirmed intact urinary bladder. Cystotomy and normograde urethral catheterization allowed localization of the ruptured urethra within the deep subcutaneous tissues of the caudal portion of the abdomen. After closure of the cystotomy and celiotomy incisions, perineal urethrostomy was performed. PMID- 2914803 TI - Give and take on campylobacteriosis. PMID- 2914804 TI - Hypersomatotropism and insulin-resistant diabetes mellitus in a cat. AB - In this report, we described the clinical, radiographic, and echocardiographic findings in a cat with hypersomatotropism and insulin-resistant diabetes mellitus. Growth hormone determinations were made because of persistent hyperglycemia despite insulin requirements exceeding 2.2 U/kg of body weight, and the acromegalic features of the cat. Also, the results of a therapeutic trial in which a long-acting analogue of somatostatin was used are discussed. PMID- 2914805 TI - Excision arthroplasty for management of coxofemoral luxation in pet birds. AB - Coxofemoral luxation, although not a common injury, can cause considerable pelvic limb dysfunction in pet birds. Luxation usually is craniodorsal, as it is in dogs. Previously recommended treatments have not always been effective in managing the injury. Sequelae can include dorsolateral deviation of the pelvic limb, with loss of function and bumblefoot in the nonluxated limb, owing to abnormal weight-bearing. Excision arthroplasty combined with a muscular sling constructed from a segment of the iliofibularis muscle was used to treat coxofemoral luxation in a hyacinth macaw, a moluccan cockatoo, and an African gray parrot. The outcome was excellent in 2 of the 3 birds. PMID- 2914806 TI - Radiophosphorus (32P) treatment of bone marrow disorders in dogs: 11 cases (1970 1987). AB - Between March 1970 and February 1987, radiophosphorus (32P) was used to treat bone marrow disorders in 6 dogs; 4 had polycythemia vera and 2 had essential thrombocythemia. Activities of 32P given initially ranged from 2.4 to 3.3 mCi/m2. Four dogs responded well to 32P treatment, with gradual resolution of high RBC or platelet counts. Two of these dogs died of intercurrent disease unrelated to their bone marrow disorder, before blood counts could be stabilized. Two dogs did not respond to the initial 32P treatment nor to additional treatments with 32P, and had clinical signs and blood counts stabilized by use of phlebotomy or chemotherapeutic agents. We reviewed and analyzed 5 other cases of bone marrow disorders in dogs treated with 32P and included the findings from their records with the records of our 6 dogs in this retrospective analysis. Of the 8 dogs with polycythemia vera treated with 32P, 5 were given a single treatment that controlled clinical signs and blood counts for the remainder of the follow-up period. Of the 3 dogs treated for thrombocytosis with 32P, 2 had blood counts that responded to a single treatment. PMID- 2914807 TI - Effects of contralateral sound on auditory-nerve responses. II. Dependence on stimulus variables. AB - The suppression by moderate-level contralateral sound of auditory-nerve-fiber responses to ipsilateral stimuli at the characteristic frequency (CF) was studied in barbiturate-anesthetized cats. The dependence of suppression strength on ipsilateral and contralateral stimulus variables, including level, frequency, bandwidth, and timing relationships, was investigated. The principal findings were: (1) Contralateral-sound suppression is greatest when the ipsilateral stimulus level is within the dynamic range of the unit. (2) When the contralateral stimuli are tones, suppression is greatest when the contralateral tone frequency is at or near CF. (3) Units with CFs above 3-4 kHz are only weakly suppressed by contralateral CF tones but more strongly suppressed by contralateral broad-band noise. (4) Continuous contralateral stimuli are significantly more effective suppressors than are gated stimuli. The characteristics of contralateral-sound suppression are compared with the physiology and anatomy of the uncrossed medial olivocochlear efferents, the subset of efferents which are the primary mediators of the effect. PMID- 2914808 TI - Acoustic responses recorded from the saccular bundle on the eighth nerve of the guinea pig. AB - Previous studies have demonstrated the existence of acoustic responses from the saccule in guinea pigs for stimulus intensities above 75 dB SPL. It is well known that the saccule receives a double afferent innervation: a bundle of the superior branch of the eighth nerve reaches its anterior part and another bundle of the inferior branch innervates its posterior part. These two bundles join just at the exit of the internal auditory meatus. An electrophysiological experiment was performed to investigate whether saccular acoustic responses could be similarly recorded from both bundles. Recordings from an electrode tip of 0.2 mm diameter were obtained in normal animals and also in animals with a complete and selective destruction of the cochlear sensory epithelium induced by treatment with an ototoxic antibiotic combined with a loop diuretic. In both normal and treated animals acoustic responses with the peculiar very short latency were specifically recorded in the area of the junction of the two bundles, they were of maximal amplitude on the bundle of the inferior branch. These data confirm in a more direct way the saccular origin of the short latency acoustic responses and indicate that they are probably conveyed in both saccular nerve bundles but mostly in that of the inferior branch of the eighth nerve. Finally these data show unequivocally that saccular acoustic responses exist in normal guinea pig ears. PMID- 2914809 TI - A degenerative disorder of the central auditory system of the gerbil. AB - A previously unidentified disorder which affects primarily the cochlear nucleus was observed in two species of gerbils, Meriones unguiculatus and M. libycus. Unusual lesions were observed in the cochlear nucleus bilaterally in all animals examined. In light and electron microscopic specimens these lesions were characterized by the presence of microcysts and vacuolar neuronal degeneration. The microcysts resembled large holes, containing trabeculae, organelles and cellular remnants. Also observed were light and dark degeneration of neuronal perikarya and degenerated axons, dendrites, and synapses, accompanied by phagocytosis. Astrocytosis was not conspicuous. In the one cochlea examined, no microcysts were observed. In young animals the microcysts were prevalent in the cochlear nerve root region and the posteroventral cochlear nucleus. In older animals the microcysts increased in number and area. In the oldest animals, the microcysts had spread to other central auditory structures, including the superior olivary complex, the nuclei of the lateral lemniscus, and the inferior colliculus. Other regions of the brain were largely free of microcysts. The etiology and behavioral manifestations of this disorder are unknown, although it is clearly neurodegenerative and perhaps genetically determined. PMID- 2914810 TI - The surface morphology of the avian tectorial membrane. AB - The structure of the tectorial membrane of the chick was evaluated by scanning electron microscopy (SEM), using standard techniques, and, for the first time, by studying unfixed tectorial membranes with video-enhanced light microscopy techniques (AVEC-DIC). The SEM pictures show a widely varying morphology, ranging from a fully perforated tectorial membrane to a completely closed upper boundary, with a smooth surface. Based on several indicators, it is concluded that the latter presents the more natural state. This was confirmed by the results of the AVEC-DIC technique, which show a highly homogeneous structure. In contrast to the bulk of the tectorial membrane, its lower surface shows discrete structures, especially regularly oriented fibril bundles. PMID- 2914811 TI - Effects of contralateral sound on auditory-nerve responses. I. Contributions of cochlear efferents. AB - The response properties of single auditory-nerve fibers in barbiturate anaesthetized cats were recorded with and without simultaneous presentation of sound to the contralateral ear. The tendons to the middle ear muscles on both sides were cut before all experiments, and contralateral stimuli were restricted to levels below the threshold for crosstalk to the ipsilateral ear. Contralateral tones and broad-band noise were found to suppress the responses of auditory-nerve afferents to ipsilateral tones at their characteristic frequency (CF), but not to tones off CF. The suppression due to contralateral sound required approximately 100-200 ms to develop and to decay. When the contralateral stimuli were tones at the CF, the strongest suppression was observed in low- and medium-spontaneous rate units with CFs between 1 and 2 kHz. The suppressive effect of contralateral sound completely disappeared immediately after severing the entire olivocochlear bundle (OCB) within the internal auditory meatus. the completeness of the OCB cuts was assessed histologically. Most of the suppressive effect remained after lesions to the OCB in the floor of the IVth ventricle which eliminated the crossed olivocochlear projection but spared most of the uncrossed projection. It is argued that this suppressive effect of contralateral sound is mediated by the uncrossed olivocochlear efferents to the outer hair cells. PMID- 2914812 TI - A rapid micro method for counting cells "in situ" using a fluorogenic alkaline phosphatase enzyme assay. AB - A new method has been developed to count cells "in situ", based on a fluorogenic enzyme assay that measures the activity of alkaline phosphatase. Increasing cell number was shown to correlate closely with alkaline phosphatase activity and this relationship did not change with time in culture. The alkaline phosphatase assay (ALP assay) was able to estimate relative cell numbers over a range from about 10(4) to 5 X 10(5) for many cell types, including Hep-2, a derivative of HeLa, several human colorectal cell lines SW1222, SW837, LS174T and HT29, a normal human diploid cell strain MRC5 and a rodent line NIH-3T3. The ALP assay is rapid and efficient, making it a useful method for studying growth assays. PMID- 2914813 TI - A simplified technique for the short-term tissue culture of rabbit corneal cells. AB - A technique for the short-term culture of pure populations of rabbit corneal endothelial and epithelial cells has been developed. Rabbit corneas were placed on concave agarose surfaces, treated briefly with a solution of trypsin and ethylenediamine tetracetic acid, and transferred, either epithelial cell surface or endothelial cell surface down, to microscope slide culture chambers. Within 6 to 12 h the epithelial cells or endothelial cells attached to the slide chamber surface and the cornea was removed, leaving behind a pure population of cells which spread out and grew to fill the surface of the slide chamber. This technique provides a simple and economic means for the reproducible initiation of primary cultures of rabbit corneal epithelial and endothelial cells for us in a variety of experiments. PMID- 2914814 TI - A continuous alveolar macrophage cell line: comparisons with freshly derived alveolar macrophages. AB - Responses of a recently developed rat alveolar macrophage cell (NR8383.1) line were compared to those of freshly derived alveolar macrophages in vitro. Marked inter- and intraspecies heterogeneity in levels of phagocytosis of unopsonized Pseudomonas aeruginosa or zymosan was noted among freshly derived alveolar macrophages from rats, rabbits, and baboons. In contrast, phagocytic responses of alveolar macrophage cell line were predictable and highly reproducible. Similar results were obtained in measuring oxidative burst, as indicated by the production of H2O2 and luminol-enhanced chemiluminescence. Responses were again highly variable in freshly derived alveolar macrophages stimulated with zymosan or phorbol myristic acetate; moreover, freshly derived alveolar macrophages exhibited a wide range of chemiluminescence activity in unstimulated cultures. Results strongly suggest that data derived from the continuous alveolar macrophage culture NR8383.1 can be extrapolated to freshly derived alveolar macrophages of various species, and in many experiments will be useful in avoiding the significant animal-to-animal variance observed among freshly derived cell preparations. PMID- 2914815 TI - Biocompatibility testing of an experimental fluoride releasing resin using human gingival epithelial cells in vitro. AB - Cell culture is a valuable method of evaluating the biocompatibility of new dental materials. The purpose of this study was to compare the in vitro biocompatibility of an experimental fluoride composite resin with fluoride and non-fluoride-releasing materials currently available. The dental materials tested were: MQ Silicate (silicate cement), KETAC-CEM and FUJI (type II glass ionomer cements), VISIO DISPERS (a light-cured, nonfluoridated, microfilled composite resin), and FR-17 (an experimental fluoride-releasing composite resin). The Smulow-Glickman (S-G) human gingival epithelial cell line, which exhibits semidifferentiated characteristics, was used in the study as a test system. Biocompatibility was quantified by counting the viable cells per unit area remaining after 24 and 48 h at two radial distances from cured specimens immersed in the cell culture medium. The test materials were observed to be most toxic to cells nearest the materials. A Time-Distance Cytotoxicity Index (TDCI) was calculated to relate the percentage of dead cells to viable cells at each diffusion distance for each exposure time compared to a nontoxic control. The relative toxicity ranking of the materials tested based on the TDCI was VISIO DISPERS (91%), FUJI (82%), FR-17 (30%), MQ Silicate (23%), and KETAC-CEM (10%), which exhibited the least toxicity. The cytotoxicity of the experimental resin FR 17 was within the range of cytotoxicity of currently accepted restorative materials. PMID- 2914816 TI - Meeting report: human fetal tissue transplantation research panel. AB - On September 14 through 16, 1988, a meeting on the use of human fetal tissue in transplantation was held at the National Institutes of Health, Bethesda Maryland, USA. The meeting sponsored by NIH for the Human Fetal Tissue Transplantation Research Panel, a consultant group to the Advisory Committee to the Director. The consultant group was convened to deal with the scientific, judicial and moral questions associated with research involving transplantation of human fetal tissue obtained after induced abortions. The first day of the meeting was devoted to presentations addressing scientific issues. Included among the speakers was Dr. Lars Olson, Professor of Neurobiology, Karolinska Institute, Stockholm, who described the use of transplanted human fetal tissue in the treatment of patients with Parkinson's disease and Dr. Eugene Redmond, Professor of Psychiatry, Yale University School of Medicine, who showed results of work with transplantation of tissue to correct induced Parkinson-like disease in monkeys. Other speakers addressed the present, past or potential use of fetal tissue in the treatment of diabetes, immune disorders, and other diseases, as well as the use of fetal cells in the production of biologicals. At the conclusion of the meeting the panel did not recommend that research be halted on fetal tissue within the context discussed, although the recommendation of the committee is not binding, and an additional assembly of the panel will probably occur before the final recommendation to an NIH advisory committee is made in November. Other meetings on this subject include a meeting on the use of fetal tissue sponsored by the American Association of Tissue Banks, March 6-7, 1989, in Washington D. C. (Crystal City) and a meeting June 10, 1989, the day before the annual meeting of the Tissue Culture Association, USA, in Orlando, Florida, on fetal cells and ownership of cultured cells and products derived from clinical specimens. Following are statements to the Human Fetal Tissue Transplantation Research Panel presented September 14, 1988, by Dr. David Barnes, Associate Professor of Biochemistry and Biophysics in the Environmental Health Sciences Center at Oregon State University, USA, who was asked to address for the panel recent advances in cell culture related to fetal tissue, and Dr. Robert E. Stevenson, Director of the American Type Culture Collection, President of the Tissue Culture Association, USA, and Chairman of the Committee on Cells and Tumors of the American Association of Tissue Banks. PMID- 2914817 TI - Power analysis of statistical methods for comparing treatment differences from limiting dilution assays. AB - Six different statistical methods for comparing limiting dilution assays were evaluated, using both real data and a power analysis of simulated data. Simulated data consisted of a series of 12 dilutions for two treatment groups with 24 cultures per dilution and 1,000 independent replications of each experiment. Data within each replication were generated by Monte Carlo simulation, based on a probability model of the experiment. Analyses of the simulated data revealed that the type I error rates for the six methods differed substantially, with only likelihood ratio and Taswell's weighted mean methods approximating the nominal 5% significance level. Of the six methods, likelihood ratio and Taswell's minimum Chi-square exhibited the best power (least probability of type II errors). Taswell's weighted mean test yielded acceptable type I and type II error rates, whereas the regression method was judged unacceptable for scientific work. PMID- 2914818 TI - Comparison of statistical methods for the analysis of limiting dilution assays. AB - This study reports the results of a critical comparison of five statistical methods for estimating the density of viable cells in a limiting dilution assay (LDA). Artificial data were generated using Monte Carlo simulation. The performance of each statistical method was examined with respect to the accuracy of its estimator and, most importantly, the accuracy of its associated estimated standard error (SE). The regression method was found to perform at a level that is unacceptable for scientific research, due primarily to gross underestimation of the SE. The maximum likelihood method exhibited the best overall performance. A corrected version of Taswell's weighted-mean method, which provides the best performance among all noniterative methods examined, is also presented. PMID- 2914819 TI - Morphologic changes induced in vitro by 2,5 hexanedione. AB - The effects of 2,5 hexanedione (2,5 HD), a metabolite of n-hexane, were investigated in different in vitro systems. A human mammary carcinoma cell line, a human melanoma cell line, and fetal mouse neuronal cells in primary culture were considered. Light and electron microscopic observations demonstrated clearly that changes in cell proliferation can be detected. Furthermore, morphologic differentiative phenomena characterized by a noticeable increase in cell protrusions and dendriticlike processes can occur. Differences in the features of these processes were also detected between the different cell lines. These data can indicate non-neuronal cells as possible further targets of the toxicant. The possibility could be hypothesized that toxic neuropathies are generalized disorders, being neuronal system exceptionally vulnerable to 2,5 HD. Moreover, results obtained suggest that the sensitivity of in vitro systems could represent a useful tool in studying the mechanisms of action of the neurotoxicant 2,5 HD. PMID- 2914821 TI - Preacademic screening for learning and behavior problems. AB - The relationship between socioeconomic status (SES) and behavior problems in children at risk for developing learning difficulties was investigated by screening 1106 children who were completing kindergarten and identifying 292 as being at-risk. Data on SES, behavior problems, and preacademic reading skills were obtained on 204 at-risk children and 181 non-at-risk controls. A larger proportion of children from upper SES made up the non-at-risk sample and a smaller proportion of upper SES children were found in the at-risk sample. Children (N = 91) who demonstrated perceptual delays and inadequate preacademic reading skills were rated by their teachers as having significantly more behavior problems than children (N = 218) who were negative for these two signs. The results suggest that some children with perceptual problems demonstrate multiple behavior problems prior to experiencing reading failure. PMID- 2914822 TI - Prevalence of unsuspected language disorders in a child psychiatric population. AB - Nonretarded 5- to 12-year-old consecutive referrals to a child psychiatric outpatient clinic underwent a routine systematic language assessment. The assessment battery comprised standardized measures of the receptive and expressive components of syntax, semantics, and phonology. Standardized behavior rating scales also were completed by parents. Of the children referred solely for a psychiatric problem, 28% had a moderate or severe language disorder that previously had not been suspected or diagnosed. These children differed from a comparison group of children with both psychiatric and language disorders in that they were younger and more likely to have an externalizing behavioral problem. The findings indicate that there is a sizeable proportion of children whose language disorders are overlooked possibly because of their disruptive behavior. This suggests the need for routine screening of language in child psychiatric populations. PMID- 2914820 TI - Automated selective dissociation of cells from different regions of multicellular spheroids. AB - In this report we describe a new apparatus which has been developed for the automated selective dissociation of multicellular spheroids into fractions of viable cells from different locations in the spheroid. This device is based on the exposure of spheroids to a 0.25% solution of trypsin under carefully controlled conditions, such that the cells are released from the outer spheroid surface in successive layers. Study of the spheroid size, number of cells per spheroid, and sections through the spheroid with increasing exposure to trypsin demonstrate the effectiveness of this technique. The technique has been successfully used on spheroids from five different cell lines over a wide range of spheroid diameters. We also present data detailing the effect of varying the dissociation temperature, the mixing speed, the trypsin concentration, and the number of spheroids being dissociated. The new apparatus has several advantages over previous selective dissociation methods and other techniques for isolating cells from different regions in spheroids, including: a) precise control over dissociation conditions, improving reproducibility; b) short time to recover cell fractions; c) ability to isolate large numbers of cells from many different spheroid locations; d) use of common, inexpensive laboratory equipment; and e) easy adaptability to new cell lines or various spheroid sizes. Applications of this method are demonstrated, including the measurement of nutrient consumption rates, regrowth kinetics, and radiation survivals of cells from different spheroid regions. PMID- 2914823 TI - Empirical classification of speech/language impairment in children. I. Identification of speech/language categories. AB - Cluster analysis was employed to classify speech/language impairment in a sample of 347 children 5 years of age. Based on scores on a variety of speech and language tests, four groups of children with similar linguistic profiles were identified. These groups were labeled high overall, low overall, poor auditory comprehension, and poor articulation. Differences among these groups according to cognitive, developmental, demographic, and audiometry variables were examined. The low overall group was most disadvantaged on all measures, the high overall group was most advantaged, and the poor articulation and poor auditory comprehension groups were intermediate. The implications of these findings for the development of a theory of the relationship between speech/language and psychiatric disorders are discussed. PMID- 2914824 TI - Empirical classification of speech/language impairment in children. II. Behavioral characteristics. AB - Behavioral symptomatology in 188 children, 5 years of age, classified according to four different speech/language profiles, is described. Information was collected from the teacher, parent, child self-report, and psychiatric interview. The results indicated that risk for psychiatric disorder, particularly ADHD, is greatest among children with general linguistic impairment. Specific deficits such as poor auditory comprehension or articulation problems were not consistently associated with behavioral disturbance. It is postulated that neurodevelopmental immaturity may be the common underlying antecedent of both linguistic impairment and psychiatric disorder. PMID- 2914825 TI - Child psychiatry program directors' ratings of residency experiences. AB - Child and adolescent psychiatry program directors' (PDs) were asked to complete survey forms to rate the importance of required residency experiences and express views on length of training. There was a 93% return rate of questionnaires sent to the 129 academic programs represented in the Society of Professors of Child and Adolescent Psychiatry. The majority of PDs favor the status quo and do not want to add or subtract from the present requirements. Experiences most favored were those with older children, adolescents, and parents, and those in the use of psychopharmacology. Least favored experiences were with cognitive therapy, research, psychological testing, and teaching. There was little interest in eliminating the internship year or residency time with adults. PMID- 2914826 TI - Resolved: day care is the best care for children under age five of working Americans. PMID- 2914827 TI - The AACAP and hospitalization for children and adolescents. PMID- 2914828 TI - Motivation for child and adolescent psychiatry. PMID- 2914830 TI - Issues in child and adolescent psychiatric hospitalization. PMID- 2914829 TI - Games infants play. PMID- 2914831 TI - Administrative issues in inpatient child and adolescent psychiatry. AB - There has been a dramatic increase in the number of inpatient child and adolescent psychiatric inpatient beds within the past 5 to 10 years. Child psychiatrists have not been trained to play a leadership role in the development and management of these units. Important issues facing the administrative child psychiatrist include the role of the medical director, the development of the clinical program, staffing of the inpatient unit, the design of the physical plant, financing of inpatient care, promotion of the services, and relationship with medical staff. PMID- 2914832 TI - Goal-directed treatment planning and the principles of brief hospitalization. AB - Contemporary economic pressures to shorten hospitalization have produced serious confusion in child psychiatry, for no adequate rationale has been proposed to replace that appropriate to long-term inpatient care. In order to address this serious deficiency, the principle of hospital stabilization is introduced and discussed, along with the concept of goal-directed planning. The steps of goal directed planning are presented. It is contended that the educational, communicative, medicolegal, and research advantages of goal-directed planning outweigh its disadvantages and that goal-direction should replace intuitive therapy-oriented planning and problem-orientation. PMID- 2914833 TI - Focal inpatient treatment planning. AB - Focal Inpatient Treatment Planning (FITP) is a new method of organizing and choosing among the many data available to the inpatient clinician. FITP emphasizes one Focal Problem, provides criteria for defining it, makes it possible to formulate the problem in operational language, channels free-ranging case discussion into workaday terms, invites the clinician to make explicit a sophisticated view of pathogenesis; including developmental, dynamic, and contextual factors, and ties formulation to intervention through explicit objectives. By requiring language that is jargon-free and accessible to patients and parents, FITP fosters empathy and alliance between the treatment community and the domain of the patient. This paper describes and illustrates FITP and provides guidelines for its implementation by an inpatient child and adolescent psychiatry service. PMID- 2914834 TI - Transactional risk model for short and intermediate term psychiatric inpatient treatment of children. AB - The transactional model provides a novel guide for the psychiatric hospital treatment of children by improving the attunement between the child and his or her important interpersonal environment. Since children's development is highly context dependent, generalization of the gains made in the hospital will largely depend upon how well the child's parents and school can internalize the hospital experience. One method to implement this transactional model is to bring the child's parents and school into the hospital to join the child's treatment team. PMID- 2914835 TI - Research on a children's psychiatric inpatient service. AB - It is widely recognized that child psychiatry needs to expand its research enterprise. Psychiatric inpatient units that serve children and adolescents should serve important roles in clinical research in child psychiatry. This paper reviews the need for research on the nature and treatment of psychiatric disorders on children's psychiatric inpatient services and discusses the resources necessary for a productive inpatient research program. The intrinsic relationship between clinical care and clinical study is emphasized. PMID- 2914836 TI - Comparison of DISC with clinicians' DSM-III diagnoses in psychiatric inpatients. AB - A sample of 163 children and adolescents, consecutively admitted to a large, private psychiatric teaching hospital, was interviewed using the child version of the Diagnostic Interview Schedule for Children (DISC-C). Patients, ages 12 to 16, were interviewed during the first month of admission. Kappa coefficients were obtained from cross-tabulated frequencies of DISC and clinician diagnoses. Agreement between clinical and DISC diagnoses was generally poor across diagnostic categories. In general, when algorithms of a higher threshold were used, the percentage of patients in a particular diagnostic group was closer to the percentage diagnosed by the clinician. Discussion focuses on factors that may contribute to the discrepancy between number and type of diagnoses that the DISC yields compared to those made by the clinicians. PMID- 2914837 TI - Psychometric properties of the K-SADS-P in an Israeli adolescent inpatient population. AB - Seventy adolescent admissions to a psychiatric unit were evaluated with a Hebrew translation of the Schedule for Affective-Disorders and Schizophrenia for School Aged Children (K-SADS-P). Interrater and test-retest reliability and mother-child agreement were evaluated for diagnoses, symptom clusters, and 20 affective symptoms. K-SADS diagnoses were also compared with 3-month unit evaluation diagnoses as a measure of consensual validity. The reliability of assessing psychosocial functioning was additionally examined. Reliability and validity of diagnoses were high and reliability of symptoms and syndromes was good to excellent. Mother-child agreement faired less well on all measures. The use of semistructured interviews and DSM-III criteria in an Israeli adolescent psychiatric setting are discussed. PMID- 2914838 TI - Clinical and demographic characteristics of child and adolescent partial hospital patients. AB - Eighteen child and adolescent partial hospital (PH) programs were surveyed through site visits. Demographic and diagnostic characteristics of 796 patients and clinical records of current and discharged patients were examined. Most current patients lived with relatives and 52% received Medicaid. Fifty-eight percent had a primary diagnosis of an externalizing disorder and 46% had been hospitalized. Forty percent of the former patients (N = 96) were discharged from PH when such services were no longer needed; another 36% left because of lack of improvement. Administrative implications of these findings are discussed. PMID- 2914839 TI - Events precipitating hospital treatment of adolescent drug abusers. AB - Recognition of and response to child and teenage drug abuse is poor. It seems that behavioral crises are necessary to bring a child and family to treatment, often after an extensive history of drug abuse. This study examines the events that occur immediately before hospitalization and lead to admission. Clusters of precipitating factors and psychosocial problems appear to accompany the use of alcohol and drugs. Recognition of these predictable behavior patterns (syndromes) may prove a more sensitive index of drug involvement than direct signs or sequalae of intoxication. PMID- 2914840 TI - An examination of social typologies in autism. AB - A system proposed by Wing and coworkers for subtyping autistic individuals on the basis of social interaction is examined in 78 autistic, 39 atypical, and 32 nonautistic, developmentally disordered individuals. Clinical ratings and questionnaire data based on the proposed subtypology were employed. Clinicians were able to reliably group both autistic and nonautistic cases into the three subtypes; these subtypes were strongly related to IQ. Issues relating to the validity and utility of this subtypology are discussed. PMID- 2914841 TI - Long-term efficacy of haloperidol in autistic children: continuous versus discontinuous drug administration. AB - The aim of this study was to evaluate the long-term efficacy of haloperidol in autistic children and to determine whether discontinuous drug administration was as effective as continuous drug administration. Sixty children, 48 males and 12 females, ages 2.3 to 7.9 years (X 5.1) completed the study. They received haloperidol over a period of 6 months followed by a 4-week drug withdrawal/placebo period. Haloperidol remained effective, and the discontinuous treatment schedule did not diminish its efficacy. Children with prominent symptoms of irritability, angry and labile affect, and uncooperativeness were the best responders to haloperidol. PMID- 2914842 TI - Tourette-like symptoms associated with neuroleptic therapy in an autistic child. AB - A 5 1/2-year-old autistic boy developed a Tourette-like syndrome after neuroleptic withdrawal. The child was studied prospectively and any abnormal movements were compared with predrug baseline assessment and information. Differential diagnosis and some of the difficulties in evaluating neuroleptic related abnormal movements are discussed. The need for a baseline assessment of patients before the administration of neuroleptics is stressed. PMID- 2914843 TI - IQ and reading progress: a test of the capacity notion of IQ. AB - Concepts such as developmental reading disorder and dyslexia have been used to refer to children whose actual reading achievement is substantially below that predicted by performance on IQ tests. Such diagnostic concepts assume that IQ sets a limit on either the level of achievement or the rate of progress of which a child is capable. This assumption was investigated in a longitudinal study of an unselected cohort of 741 children whose reading achievement was assessed at ages 7, 9, 11, and 13 years. Findings on rates of progress and levels of achievement clearly indicate that IQ does not set a limit on reading progress, even in extreme low IQ children. Thus, the use of IQ tests to determine achievement potential in reading appears unwarranted. PMID- 2914844 TI - Involvement of coenzyme A thioesters in anaerobic metabolism of 4-hydroxybenzoate by Rhodopseudomonas palustris. AB - The initial steps of anaerobic 4-hydroxybenzoate degradation were studied in whole cells and cell extracts of the photosynthetic bacterium Rhodopseudomonas palustris. Illuminated suspensions of cells that had been grown anaerobically on 4-hydroxybenzoate and were assayed under anaerobic conditions took up [U-14C]4 hydroxybenzoate at a rate of 0.6 nmol min-1 mg of protein-1. Uptake occurred with high affinity (apparent Km = 0.3 microM), was energy dependent, and was insensitive to external pH in the range of 6.5 to 8.2 Very little free 4 hydroxybenzoate was found associated with cells, but a range of intracellular products was formed after 20-s incubations of whole cells with labeled substrate. When anaerobic pulse-chase experiments were carried out with cells incubated on ice or in darkness, 4-hydroxybenzoyl coenzyme A (4-hydroxybenzoyl-CoA) was formed early and disappeared immediately after addition of excess unlabeled substrate, as would be expected of an early intermediate in 4-hydroxybenzoate metabolism. A 4-hydroxybenzoate-CoA ligase activity with an average specific activity of 0.7 nmol min-1 mg of protein-1 was measured in the soluble protein fraction of cells grown anaerobically on 4-hydroxybenzoate. 4-Hydroxybenzoyl-CoA was the sole product formed from labeled 4-hydroxybenzoate in the ligase reaction mixture. 4 Hydroxybenzoate uptake and ligase activities were present in cells grown anaerobically with benzoate, 4-hydroxybenzoate, and 4-aminobenzoate and were not detected in succinate-grown cells. These results indicate that the high-affinity uptake of 4-hydroxybenzoate by R. palustris is due to rapid conversion of the free acid to its CoA derivative by a CoA ligase and that this is also the initial step of anaerobic 4-hydroxybenzoate degradation. PMID- 2914845 TI - Genetic evidence for an Azotobacter vinelandii nitrogenase lacking molybdenum and vanadium. AB - We have constructed a strain of Azotobacter vinelandii which has deletions in the genes for both the molybdenum (Mo) and vanadium (V) nitrogenases. This strain fixed nitrogen in medium that did not contain Mo or V. Growth and nitrogenase activity were inhibited by Mo and V. In highly purified medium, growth was limited by iron. Addition of other metals (Co, Cr, Cu, Mn, Ni, Re, Ti, W, and Zn) did not stimulate growth. Like the V-nitrogenase, the nitrogenase synthesized by the double deletion strain reduced acetylene to both ethylene and ethane (C2H6/C2H4 ratio, 0.046). There was an approximately 10-fold increase in ethane production when Mo was added to the deletion strain grown in medium lacking Mo and V. This change in reactivity may be due to the incorporation of an Mo containing cofactor into the nitrogenase synthesized by the double-deletion strain. A strain synthesizing the V-nitrogenase did not show a similar increase in ethane production. The growth characteristics of the double-deletion strain, together with the metal composition reported for a nitrogenase isolated from a tungstate-tolerant strain lacking genes for the molydenum enzyme grown in the absence of Mo and V (J. R. Chisnell, R. Premakumar, and P. E. Bishop, J. Bacteriol. 170:27-33, 1988) show that A. vinelandii can synthesize a nitrogenase which lacks both Mo and V. Reduction of dinitrogen by nitrogenase can therefore occur at a center lacking both these metals. PMID- 2914846 TI - Three-dimensional structure of an open form of the surface layer from the fish pathogen Aeromonas salmonicida. AB - Cell-free culture supernatants of a lipopolysaccharide (LPS) O-polysaccharide deficient, single-insertion transposon mutant of the tetragonal surface protein array (S layer)-containing fish pathogen Aeromonas salmonicida were examined by electron microscopy. Negative staining showed that the S layer was released as sheets of tetragonal material, indicating that although surface retention of assembled S layer requires the presence of wild-type LPS oligosaccharides, initial assembly of S-layer subunits into sheets does not require the presence of O-polysaccharide chains. The three-dimensional structure of the S layer was reconstructed from tilted micrographs of the released sheets. Horizontal sections through this reconstruction showed that the released sheets were composed of two identical S layers that were perfectly in register. The reconstructed layer had a lattice constant of 12.5 nm. At a resolution of 1.6 nm, the layer consisted of a major tetragon at one fourfold axis of symmetry and a minor tetragon at the second fourfold axis of symmetry. The core, composed of four of the major domains, contained a large depression and was located toward the inside of the layer. The minor tetragon provided connectivity within the layer and was located toward the outer surface of the layer. Projections through the double layer gave a type I (closed) pattern (M. Stewart, T. J. Beveridge, and T. J. Trust, J. Bacteriol. 166:120-127, 1986), yet projections through the single layer indicated that the type II (open) pattern was present. This open pattern was indistinguishable from that seen in S layer released from the surfaces of wild type cells. PMID- 2914847 TI - Identification by sequence analysis of two-site posttranslational processing of the cysteine-rich outer membrane protein 2 of Chlamydia trachomatis serovar L2. AB - The 60,000-molecular-weight cysteine-rich outer membrane protein (OMP2) from Chlamydia trachomatis participates in the disulfide-mediated outer-membrane organization unique to this organism. In addition, this protein is a primary focus of the host immune response. We cloned and sequenced the gene for OMP2 from C. trachomatis serovar L2. A lambda gt11 recombinant that expressed an antigenic portion of this protein was selected by antibody screening and provided a probe for the selection in lambda 1059 of a clone containing the entire gene. DNA sequencing of this clone identified one open reading frame of 1,641 base pairs, starting with a methionine codon and coding for a polypeptide with a molecular weight of 58,792. Amino-terminal protein sequencing and analysis of the translated DNA sequence demonstrated that processing at alternate signal peptide cleavage sites accounts for the molecular-weight polymorphism of this protein. The mature proteins had a net positive charge and contained 24 cysteine residues. PMID- 2914848 TI - Phenoxyacetic acid degradation by the 2,4-dichlorophenoxyacetic acid (TFD) pathway of plasmid pJP4: mapping and characterization of the TFD regulatory gene, tfdR. AB - Plasmid pJP4 enables Alcaligenes eutrophus JMP134 to degrade 3-chlorobenzoate and 2,4-dichlorophenoxyacetic acid (TFD). Plasmid pRO101 is a derivative of pJP4 obtained by insertion of Tn1721 into a nonessential region of pJP4. Plasmid pRO101 was transferred by conjugation to several Pseudomonas strains and to A. eutrophus AEO106, a cured isolate of JMP134. AEO106(pRO101) and some Pseudomonas transconjugants grew on TFD. Transconjugants with a chromosomally encoded phenol hydroxylase also degraded phenoxyacetic acid (PAA) in the presence of an inducer of the TFD pathway, namely, TFD or 3-chlorobenzoate. A mutant of one such phenol degrading strain, Pseudomonas putida PPO300(pRO101), grew on PAA as the sole carbon source in the absence of inducer. This isolate carried a mutant plasmid, designated pRO103, derived from pRO101 through the deletion of a 3.9-kilobase DNA fragment. Plasmid pRO103 constitutively expressed the TFD pathway, and this allowed the metabolism of PAA in the absence of the inducer, TFD. Complementation of pRO103 in trans by a DNA fragment corresponding to the fragment deleted in pRO101 indicates that a negative control-regulatory gene (tfdR) is located on the BamHI E fragment of pRO101. Other subcloning experiments resulted in the cloning of the tfdA monooxygenase gene on a 3.5-kilobase fragment derived from pRO101. This subclone, in the absence of other pRO101 DNA, constitutively expressed the tfdA gene and allowed PPO300 to grow on PAA. Preliminary evidence suggests that the monooxygenase activity encoded by this DNA fragment is feedback-inhibited by phenols. PMID- 2914849 TI - Isolation and nucleotide sequencing of an aminocyclitol acetyltransferase gene from Streptomyces rimosus forma paromomycinus. AB - A gene (aacC7) encoding an aminocyclitol 3-N-acetyltransferase type VII [AAC(3) VII] from Streptomyces rimosus forma paramomycinus NRRL 2455 was cloned in the Streptomyces plasmid pIJ702 and expressed in Streptomyces lividans 1326. Subcloning experiments located the aacC7 structural gene on a 1.05-kilobase DNA sequence. The direction of transcription of aacC7 was determined by using riboprobes synthesized in vitro from a DNA fragment internal to the gene. A DNA segment encoding the AAC(3)-VII activity and comprising 1,495 base pairs was sequenced. The aacC7 gene was located in an open reading frame of 864 base pairs that encoded a polypeptide of Mr 31,070, consistent with the Mr (32,000) of the AAC(3)-VII enzyme as determined by physicochemical methods. High-resolution S1 nuclease mapping suggested that transcription starts at or near the A residue of the ATG initiator codon. A DNA fragment from the 5' region of aacC7 had promoter activity in the promoter-probe plasmid pIJ486. The -10 and -35 regions of this fragment showed limited sequence resemblance to other Streptomyces promoters. The primary structure of the AAC(3)-VII enzyme showed strong homology with those of the AAC(3)-III and AAC(3)-IV enzymes encoded by plasmids in gram-negative bacterial genera. Upstream of the aacC7 gene was an open reading frame of 357 nucleotides which did not appear to be involved in controlling the expression of the aacC7 gene. PMID- 2914850 TI - Chromosome and cell wall segregation in Streptococcus faecium ATCC 9790. AB - Segregation was studied by measuring the positions of autoradiographic grain clusters in chains formed from single cells containing on average less than one radiolabeled chromosome strand. The degree to which chromosomal and cell wall material cosegregated was quantified by using the methods of S. Cooper and M. Weinberger, dividing the number of chains labeled at the middle. This analysis indicated that in contrast to chromosomal segregation in Escherichia coli and, in some studies, to that in gram-positive rods, chromosomal segregation in Streptococcus faecium was slightly nonrandom and did not vary with growth rate. Results were not significantly affected by strand exchange. In contrast, labeled cell wall segregated predominantly nonrandomly. PMID- 2914851 TI - Pattern of action of Bacillus stearothermophilus neopullulanase on pullulan. AB - The action of neopullulanase from Bacillus stearothermophilus on many oligosaccharides was tested. The enzyme hydrolyzed not only alpha-(1----4) glucosidic linkages but also specific alpha-(1----6)-glucosidic linkages of several branched oligosaccharides. When pullulan was used as a substrate, panose, maltose, and glucose, in that order, were produced as final products at a final molar ratio of 3:1:1. According to these results, we proposed a model for the pattern of action of neopullulanase on pullulan as follows. In the first step, the enzyme hydrolyzes only alpha-(1----4)-glucosidic linkages on the nonreducing side of alpha-(1----6) linkages of pullulan and produces panose and several intermediate products composed of some panose units. In the second step, taking 6(2)-O-alpha-(6(3)-O-alpha-glucosyl-maltotriosyl)-maltose as an example of one of the intermediate products, the enzyme hydrolyzes either alpha-(1----4) (the same position as that described above) or alpha-(1----6) linkages and produces panose or 6(3)-O-alpha-glucosyl-maltotriose plus maltose, respectively. In the third step, the alpha-(1----4) linkage of 6(3)-O-alpha-glucosyl-maltotriose is hydrolyzed by the enzyme, and glucose and another panose are produced. To confirm the model of the pattern of action, we extracted intermediate products produced from pullulan by neopullulanase and analyzed the structures by glucoamylase, pullulanase, and neopullulanase analyses. The experimental results supported the above-mentioned model of the pattern of action of neopullulanase on pullulan. PMID- 2914852 TI - Hypervariability, a new phenomenon of genetic instability, related to DNA amplification in Streptomyces ambofaciens. AB - The wild-type strain Streptomyces ambofaciens DSM 40697 exhibits a high degree of genetic instability. Pigment-defective colonies were observed in the progeny of wild-type colonies at a frequency of about 0.01. While only 13% of these pigment defective colonies gave rise to homogeneous progeny exhibiting the mutant parental phenotype, 87% of the mutant colonies gave rise to hetergeneous progeny without a preponderant phenotype. This new phenomenon of instability was called hypervariability. In addition, 21% of the mutant strains arising in hypervariable progeny contained highly reiterated DNA sequences, while amplified DNA sequences could be detected in neither stable pigment-defective mutant clones nor in wild type clones. These results indicate a frequent association between genetic instability and hypervariability and a frequent association between hypervariability and amplification of DNA sequences. PMID- 2914853 TI - Structure and glycosylation of lipoteichoic acids in Bacillus strains. AB - The occurrence, structure, and glycosylation of lipoteichoic acids were studied in 15 Bacillus strains, including Bacillus cereus (4 strains), Bacillus subtilis (5 strains), Bacillus licheniformis (1 strain), Bacillus polymyxa (2 strains), and Bacillus circulans (3 strains). Whereas in the cells of B. polymyxa and B. circulans neither lipoteichoic acid nor related amphipathic polymer could be detected, the cells of other Bacillus strains were shown to contain lipoteichoic acids built up of poly(glycerol phosphate) backbone chains and hydrophobic anchors [gentiobiosyl(beta 1----1/3)diacylglycerol or monoacylglycerol]. The lipoteichoic acid chains of the B. licheniformis strain and three of the B. subtilis strains had N-acetylglucosamine side branches, but those of the B. cereus strains and the remaining two B. subtilis strains did not. The membranes of the B. licheniformis strain and the first three B. subtilis strains exhibited enzyme activities for the synthesis of beta-N-acetylglucosamine-P-polyprenol and for the transfer of N-acetylglucosamine from this glycolipid to endogenous acceptors presumed to be lipoteichoic acid precursors. In contrast, the membranes of the other strains lacked both or either of these two enzyme activities. The correlation between the occurrence of N-acetylglucosamine-linked lipoteichoic acids and the distribution of these enzymes is consistent with the previously proposed function of beta-N-acetylglucosamine-P-polyprenol as a glycosyl donor in the introduction of alpha-N-acetylglucosamine branches to lipoteichoic acid backbone chains. PMID- 2914854 TI - Peptidoglycan-polysaccharide complex in the cell wall of the filamentous prochlorophyte Prochlorothrix hollandica. AB - A peptidoglycan-polysaccharide complex composed of N-acetylglucosamine, N acetylmuramic acid, muramic acid 6-phosphate, L-alanine, D-alanine, D-glutamic acid, meso-diaminopimelic acid, N-acetylmannosamine, mannose, galactose, glucose, and phosphate was isolated from cell walls of the filamentous prochlorophyte Prochlorothrix hollandica; this complex was similar in chemical composition and structure to that found in cyanobacteria. Peptide patterns of partial acid hydrolysates of the isolated peptidoglycan revealed an A1 gamma structure with direct cross-linkage (m-diaminopimelic acid-D-alanine) of the peptide side chains. The degree of cross-linkage (63%) was found to be in the range of values obtained for gram-positive bacteria and cyanobacteria. PMID- 2914855 TI - Characterization of three choline transport activities in Rhizobium meliloti: modulation by choline and osmotic stress. AB - Choline has both a nutritional and osmoregulatory role in Rhizobium meliloti (T. Bernard, J. A. Pocard, B. Perroud, and D. Le Rudulier, Arch. Microbiol. 143:359 364, 1986). In view of this fact, choline transport was studied in R. meliloti 102F34 to determine how the rate of choline uptake is modulated. The effects of the cultural conditions on the kinetics of transport are presented. A high affinity activity and a low-affinity activity were found in cells grown in minimal medium. The addition of 0.3 M NaCl or other osmolytes to the medium resulted in a marked decrease in the high-affinity activity, whereas the low affinity activity remained fairly constant. Furthermore, results from osmotic upshock and downshock experiments indicate that the response of the cell to high osmolarity is rapid; hence, the mechanism of regulation by salt likely does not involve gene induction. A second high-affinity transport activity was induced by choline itself. Like the constitutive low-affinity transport activity, this activity was not greatly altered when the cells were grown in media of elevated osmotic strength. We conclude that although all three kinetically distinct transport systems are efficient at low osmolarity, only the induced high- and low affinity activities are important for osmoregulation. The characteristics of the three transport activities from R. meliloti are compared with those from other bacterial species that use choline for growth and/or osmoregulation. PMID- 2914856 TI - Roles of flagella, lipopolysaccharide, and a Ca2+-dependent cell surface protein in attachment of Rhizobium leguminosarum biovar viciae to pea root hair tips. AB - The relationship between Ca2+-dependent cell surface components of Rhizobium leguminosarum biovar viciae, motility, and ability to attach to pea root hair tips was investigated. In contrast to flagella and lipopolysaccharide, a small protein located on the cell surface was identified as the Ca2+-dependent adhesin. PMID- 2914857 TI - Protoporphyrinogen oxidation, a step in heme synthesis in soybean root nodules and free-living rhizobia. AB - Extracts of the crude bacteroid fraction of symbiotically grown Bradyrhizobium japonicum were much more active in oxidizing protoporphyrinogen to protoporphyrin than were extracts of cells grown under free-living conditions, especially when assayed in atmospheres containing only traces of oxygen. This correlates with the higher heme content of the microaerophilic nodules. Furthermore, the high level of oxidative activity in the crude bacteroid fraction was associated with an uncharacterized membrane fraction, probably of plant origin, that was separable from the bacteroids by Percoll gradient centrifugation. PMID- 2914858 TI - Nucleotide sequence of the gene for cholesterol oxidase from a Streptomyces sp. AB - The nucleotide sequence of a 2.1-kilobase-pair fragment containing the Streptomyces choA gene, which codes a secreted cholesterol oxidase, was determined. A single open reading frame encodes a mature cholesterol oxidase of 504 amino acids, with a calculated Mr of 54,913. The leader peptides extend over 42 amino acids and have the characteristics of a signal sequence, including basic amino acids near the amino terminus and a hydrophobic core near the signal cleavage site. Analyses of the total amino acid composition and amino acid sequencing of the first 21 amino acids from the N terminus of the purified extracellular enzyme agree with the values deduced from nucleotide sequencing data. PMID- 2914859 TI - Sequence analysis of the agrA gene encoding beta-agarase from Pseudomonas atlantica. AB - The nucleotide sequence of the agrA gene encoding an extracellular beta-agarase of Pseudomonas atlantica was determined. An open reading frame of 1,515 nucleotides which corresponded to agrA was found. The nucleotide sequence predicts a primary translation product of 504 amino acids and Mr 57,486. Comparison of the deduced amino acid sequences of beta-agarase from P. atlantica and the extracellular beta-agarase from Streptomyces coelicolor A3(2) suggests that these proteins share several domains in common. PMID- 2914860 TI - Chemotaxis mutants of Spirochaeta aurantia. AB - Five Spirochaeta aurantia chemotaxis mutants were isolated. One mutant (the che 101 mutant) never reversed, one (the che-200 mutant) flexed predominantly, two (the che-300 and che-400-1 mutants) exhibited elevated reversal frequencies, and one (the che-400 mutant) exhibited chemotactically unstimulated behavior similar to that of the wild-type strain. The che-101 and che-400 mutants were essentially nonchemotactic, whereas the che-200, che-300, and che-400-1 mutants showed impaired chemotactic responses. Protein methylation in response to attractant addition appeared normal in all of the mutants. Compared with the wild type, all of the mutants exhibited significantly altered membrane potential responses to the attractant xylose. PMID- 2914861 TI - Isolation and characterization of an archaebacterial viruslike particle from Methanococcus voltae A3. AB - Small amounts of a 23-kilobase covalently closed circular DNA molecule were isolated from unwashed cells of Methanococcus voltae A3. Further investigation indicated the presence of greater quantities of the circular DNA in the culture supernatant, complexed with protein in a manner rendering the DNA resistant to DNase. Electron-microscopic examination of supernatant material revealed the presence of particles which morphologically resemble virus. Phenol extraction of viruslike particle preparations resulted in the recovery of DNase-sensitive open circular DNA molecules. As many as 30 viruslike particles per cell were recovered from some cultures. Hybridization data clearly indicated the presence of a chromosomally integrated copy of the viruslike particle DNA. Although M. voltae PS was not observed to produce viruslike particles, DNA homologous to the viruslike particle DNA was detected in its chromosome. A mutant of M. voltae A3 was isolated which produced no particles; its DNA was deleted for 80% of the integrated viruslike particle DNA. Despite any similarities to lysogenic bacteriophages of eubacteria, neither infectivity nor inducibility of the viruslike particles could be demonstrated. PMID- 2914862 TI - Multiple and tandemly arranged promoters of the cell wall protein gene operon in Bacillus brevis 47. AB - The genes encoding the major cell wall proteins, middle wall protein and outer wall protein, of Bacillus brevis 47 constitute a cotranscriptional unit (cwp [cell wall protein gene] operon). Primer extension assay of cwp operon transcripts showed the existence of six different 5' ends. This confirmed the results of the previous S1 nuclease protection assay and suggested the existence of several tandemly arranged promoters in the 5' region of the cwp operon. Promoter probe vectors carrying the Bacillus licheniformis alpha-amylase gene were constructed and used for deletion analysis of the 5' region. Three (P1, P2, and P3) of the six suggested promoters were shown to be located within three distinct fragments derived from the 5' region. The -35 and -10 regions of the P1 and P3 promoters resemble the consensus sequence recognized by the sigma-43-type RNA polymerase of Bacillus subtilis. The P2 promoter resembles only the consensus sequence in the -10 region. The P1 and P3 promoters were used to the same extents in Bacillus subtilis as in B. brevis, whereas the P2 promoter was used much less frequently in B. subtilis than in B. brevis. The P2 promoter is used constitutively in B. brevis 47 at all stages of growth, whereas P3 is used only at the exponential phase of growth. P2 could be a promoter of an unknown type that is preferentially used in B. brevis and might be responsible for the constitutive synthesis and secretion of the cell wall proteins into the medium at the stationary phase of growth. PMID- 2914863 TI - Role of the flagellum in cell-cycle-dependent expression of bacteriophage receptor activity in Caulobacter crescentus. AB - The rate of adsorption of Caulobacter bacteriophage phi CbK to Caulobacter crescentus is dependent on the structural integrity of the flagellum. Cells lacking part or all of the flagellum because of either mutation or mechanical shear were defective in adsorption, and the extent of the defect in adsorption reflected the amount of flagellar structure missing. Maximal adsorption rates were also dependent on cellular motility and energy metabolism, since adsorption to cells with paralyzed flagella was slower than adsorption to motile cells and inhibition of cellular energy metabolism with azide also reduced adsorption rates, even for nonmotile cells. Nevertheless, the flagellum is not the receptor for phage phi CbK, since flagellumless mutants adsorbed phi CbK at detectable rates. While some portion of the fluctuation in the phi CbK receptor activity during the C. crescentus cell cycle can be ascribed to the periodicity of flagellar loss and reappearance, the phage receptor activity remaining in flagellumless mutants was periodic in the cell cycle. Therefore, the periodic expression of phage receptor activity is an intrinsic property of the C. crescentus cell cycle, although the amplitude of the oscillation may be altered by the periodic expression of flagellar motility. PMID- 2914864 TI - Modulation of alcohol dehydrogenase isoenzyme levels in Zymomonas mobilis by iron and zinc. AB - Zymomonas mobilis is an unusual microorganism which utilizes both iron-containing alcohol dehydrogenase (ADHII) and zinc-containing alcohol dehydrogenase (ADHI) isoenzymes during fermentative growth. This organism is obligately ethanologenic, and alcohol dehydrogenase activity is essential. The activities of ADHI and ADHII were altered by supplementing growth medium with iron or zinc salts and by iron starvation. Growth under iron-limiting conditions (chelators, minimal medium) reduced ADHII activity but did not prevent the synthesis of the ADHII protein. The inactive form of this enzyme appeared quite stable, was not renatured by iron addition, and persisted in the cell. The iron-induced increase in ADHII activity required de novo synthesis which was blocked by antibiotic additions. The ability of Z. mobilis to synthesize ADHII and ADHI may be advantageous in nature. PMID- 2914865 TI - Immunological characterization of Rhizobium leguminosarum outer membrane antigens by use of polyclonal and monoclonal antibodies. AB - Surface antigens of Rhizobium leguminosarum biovar viciae strain 248 were characterized by using polyclonal and monoclonal antibodies. With Western immunoblotting as the criterion, an antiserum raised against living whole cells recognized mainly flagellar antigens and the O-antigen-containing part of the lipopolysaccharide (LPS). Immunization of mice with a peptidoglycan-outer membrane complex yielded eight monoclonal antibodies, of which three reacted with LPS and five reacted with various sets of outer membrane protein antigens. The observation that individual monoclonal antibodies react with sets of related proteins is discussed. Studies of the influence of calcium deficiency and LPS alterations on surface antigenicity showed that in normally grown wild-type cells, the O-antigenic side chain of LPS blocks binding of an antibody to a deeper-lying antigen. This antigen is accessible to antibodies in cells grown under calcium limitation as well as in O-antigen-lacking mutant cells. Two of the antigen groups which can be distinguished in cell envelopes of free-living bacteria were depleted in cell envelopes of isolated bacteroids, indicating that the monoclonal antibodies could be useful tools for studying the differentiation process from free-living bacteria to bacteroids. PMID- 2914866 TI - Purification and properties of glutathione transferase from Issatchenkia orientalis. AB - Glutathione transferase (GST) (EC 2.5.1.18) was purified from a cell extract of Issatchenkia orientalis, and two GST isoenzymes were isolated. They had molecular weights of 37,500 and 40,000 and were designated GST Y-1 and GST Y-2, respectively. GST Y-1 and GST Y-2 gave single bands with molecular weights of 22,000 and 23,500, respectively, on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. GST Y-1 and GST Y-2 were immunologically distinguished from each other. GST Y-1 showed specific activity 10.4-times and 6.0-times higher when 1 chloro-2,4-dinitrobenzene and o-dinitrobenzene were used as substrates, respectively, than GST Y-2. GST activity was not detected for either isoenzyme when other substrates such as bromosulfophthalein and trans-4-phenyl-3-buten-2 one were used. GST Y-1 and GST Y-2 had Km values of 0.51 and 0.75 mM for glutathione, respectively, and of 0.16 and 4.01 mM for 1-chloro-2,4 dinitrobenzene. GST Y-1 was significantly inhibited by Cibacron blue 3G-A, and GST Y-2 was significantly inhibited by bromosulfophthalein. PMID- 2914867 TI - Translation and processing of Bacillus amyloliquefaciens extracellular RNase. AB - Bacillus amyloliquefaciens extracellular RNase has been previously cloned and expressed in Bacillus subtilis. Site-specific mutagenesis experiments have identified codon -39 as the start site of translation. We have determined the primary signal peptide cleavage site of preprobarnase and propose a pathway for the conversion of probarnase to mature barnase. PMID- 2914868 TI - Spermidine synthesis by Pseudomonas sp. strain Kim, previously reported to lack this polyamine. AB - Pseudomonas sp. strain Kim has previously been reported to be the only known naturally occurring organism lacking spermidine. We now show that it synthesizes this polyamine. The apparent lack of intracellular levels of spermidine results from an efficient conversion of spermidine to putrescine and hydroxyputrescine. PMID- 2914869 TI - Isolation of a third lipoamide dehydrogenase from Pseudomonas putida. AB - Pseudomonads are the only organisms so far known to produce two lipoamide dehydrogenases (LPDs), LPD-Val and LPD-Glc. LPD-Val is the specific E3 component of branched-chain oxoacid dehydrogenase, and LPD-Glc is the E3 component of 2 ketoglutarate and possibly pyruvate dehydrogenases and the L-factor of the glycine oxidation system. Three mutants of Pseudomonas putida, JS348, JS350, and JS351, affected in lpdG, the gene encoding LPD-Glc, have been isolated; all lacked 2-ketoglutarate dehydrogenase, but two, JS348 and JS351, had normal pyruvate dehydrogenase activity. The pyruvate and 2-ketoglutarate dehydrogenases of the wild-type strain of P. putida were both inhibited by anti-LPD-Glc, but the pyruvate dehydrogenase of the lpdG mutants was not inhibited, suggesting that the mutant pyruvate dehydrogenase E3 component was different from that of the wild type. The lipoamide dehydrogenase present in one of the lpdG mutants, JS348, was isolated and characterized. This lipoamide dehydrogenase, provisionally named LPD 3, differed in molecular weight, amino acid composition, and N-terminal amino acid sequence from LPD-Glc and LPD-Val. LPD-3 was clearly a lipoamide dehydrogenase as opposed to a mercuric reductase or glutathione reductase. LPD-3 was about 60% as effective as LPD-Glc in restoring 2-ketoglutarate dehydrogenase activity and completely restored pyruvate dehydrogenase activity in JS350. These results suggest that LPD-3 is a lipoamide dehydrogenase associated with an unknown multienzyme complex which can replace LPD-Glc as the E3 component of pyruvate and 2-ketoglutarate dehydrogenases in lpdG mutants. PMID- 2914870 TI - Buoyant density, growth rate, and the cell cycle in Streptococcus faecium. AB - The buoyant density in rapidly growing Streptococcus faecium 9790 cells varies over the cell cycle, in contrast to the density in Escherichia coli. Buoyant density in S. faecium was measured by using Percoll (Pharmacia Fine Chemicals, Piscataway, N.J.) density gradients. We found that the mean and coefficient of variation of the population density increased with growth rate; and within a population, the mean cell volume, which was measured electronically, increased with density. These results were compared with electron microscopic measurements of the size distributions of cell wall growth sites within each fraction of the density gradient. As the density increased within a population, the frequency of large cells increased and the frequency of newly initiated cell wall growth sites increased. These effects were more marked as the growth rate increased. Next, these data were regrouped by cell size by using the size of the central growth site as an index of cell cycle stage. Each frequency value was weighted by the proportion of the population represented by that density fraction. Then, the average buoyant density was calculated for each value of cell size. In all cell populations, the density decreased and then increased as the central site enlarged. Peripheral growth sites were initiated as density reached a maximum. At faster growth rates, density increased more steeply, and new peripheral growth sites opened up at a higher frequency. We suggest that the rate at which density increases during the cell cycle correlates with the initiation of new cell wall growth sites. PMID- 2914871 TI - Iron regulation of swarmer cell differentiation of Vibrio parahaemolyticus. AB - Vibrio parahaemolyticus has two distinct cell types, the swimmer cell and the swarmer cell, adapted for locomotion in different circumstances. The swimmer cell, produced when the bacterium is grown in liquid media, is a short rod with a single sheathed polar flagellum. The swarmer cell, produced when V. parahaemolyticus is grown on solidified media, is greatly elongated and synthesizes, in addition to the polar flagellum, numerous unsheathed lateral flagella which are responsible for translocation over surfaces. We are interested in understanding how this bacterium differentiates in response to contact with surfaces and have determined in earlier work that the polar flagellum acts as a tactile sensor which controls transcription of genes (laf) encoding the swarmer cell phenotype. Surface recognition involves sensing of forces that obstruct movement of the polar flagellum. In this report we show that a second signal, iron limitation, is also required for swarmer cell differentiation. Production of lateral flagella occurred only when polar flagellar function was perturbed and iron-limiting growth conditions were imposed. The same conditions were required to induce light production in strains of V. parahaemolyticus in which a laf gene was transcriptionally fused to the lux operon encoding the enzymes for bioluminescence. The lafA gene encoding the lateral flagellin subunit was cloned and used in Northern (RNA) blot measurements. Examination of mRNA levels revealed that transcription of lafA is dependent on growth in iron-depleted media. The control of differentiation by multiple environmental stimuli is discussed. PMID- 2914872 TI - Cloning, sequencing, and characterization of the principal acid phosphatase, the phoC+ product, from Zymomonas mobilis. AB - The Zymomonas mobilis gene encoding acid phosphatase, phoC, has been cloned and sequenced. The gene spans 792 base pairs and encodes an Mr 28,988 polypeptide. This protein was identified as the principal acid phosphatase activity in Z. mobilis by using zymograms and was more active with magnesium ions than with zinc ions. Its promoter region was similar to the -35 "pho box" region of the Escherichia coli pho genes as well as the regulatory sequences for Saccharomyces cerevisiae acid phosphatase (PHO5). A comparison of the gene structure of phoC with that of highly expressed Z. mobilis genes revealed that promoters for all genes were similar in degree of conservation of spacing and identity with the proposed Z. mobilis consensus sequence in the -10 region. The phoC gene contained a 5' transcribed terminus which was AT rich, a weak ribosome-binding site, and less biased codon usage than the highly expressed Z. mobilis genes. PMID- 2914873 TI - Demonstration, characterization, and mutational analysis of NahR protein binding to nah and sal promoters. AB - The nahR gene of plasmid NAH7 of Pseudomonas putida encodes a 36-kilodalton polypeptide which activates transcription of the nah and sal operons in response to the inducer salicylate. A gel mobility shift assay was used to identify a DNA binding activity which was present only in extracts from either P. putida or Escherichia coli containing a functional nahR gene. The binding activity was highly specific for DNA containing the nah or sal promoters, but the apparent affinity for the promoters was not altered by the presence of salicylate. DNase I protection experiments with a partially purified NahR protein preparation showed that NahR protects both nah and sal promoter sequences between -82 and -47. The location and amount of protection were not dramatically altered by the presence of salicylate. In vitro mutagenesis was used to make mutations in the protected region of the sal promoter. Analysis of the mutants showed that binding of NahR is required for transcription activation and identified two nucleotides in the protected region that are essential for binding and activation by NahR. PMID- 2914874 TI - Cloning and heterologous expression in Streptomyces lividans of Streptomyces rimosus genes involved in oxytetracycline biosynthesis. AB - The anhydrotetracycline (ATC) oxygenase enzyme which carries out the conversion of ATC to dehydrotetracycline was purified and the N-terminal amino acid sequence was determined. The sequence displays a significant similarity to that of the p hydroxybenzoate hydroxylase from Pseudomonas fluorescens. This is consistent with the activity of the oxygenase, i.e., addition of a hydroxyl moiety to an aromatic ring structure. Oligonucleotide probes were designed and used to clone the corresponding fragment of chromosomal DNA from Streptomyces rimosus. This DNA fragment was used to screen a cosmid library, allowing the isolation of flanking DNA sequences. Surprisingly, the gene was located within the previously cloned cluster of genes involved in the synthesis of the biosynthetic intermediate ATC and not as had been expected (P. M. Rhodes, N. Winskill, E. J. Friend, and M. Warren, J. Gen. Microbiol. 124:329-338, 1981) at a separate locus on the other side of the chromosome. Subcloning of an appropriate DNA fragment from one of the cosmid clones onto pIJ916 produced Streptomyces lividans transformants which synthesized oxytetracycline. PMID- 2914875 TI - Plasmid-determined inducible efflux is responsible for resistance to cadmium, zinc, and cobalt in Alcaligenes eutrophus. AB - In Alcaligenes eutrophus CH34, resistance to chromate is plasmid determined, inducible, and based on decreased net accumulation of the metal anion. Plasmid encoded resistances to zinc, cadmium, cobalt, and nickel are resulting from inducible, energy-dependent cation efflux systems. PMID- 2914876 TI - Cloning, nucleotide sequence, and characterization of genes encoding the secretion function of the Pasteurella haemolytica leukotoxin determinant. AB - The structural gene of the Pasteurella haemolytica leukotoxin determinant is highly homologous to that of the Escherichia coli hemolysin determinant, which also encodes a specialized set of genes involved in the secretion of the hemolysin. In this report, we describe the cloning and nucleotide sequence of the analogous secretion genes from P. haemolytica which make up the remainder of the leukotoxin determinant. The secretion genes were cloned directly from the P. haemolytica chromosome to form the recombinant plasmid pPH5B. By subcloning the secretion genes together with the leukotoxin structural gene, the cloned leukotoxin determinant was reconstructed on a single plasmid, pLKT52, which directs the synthesis of active leukotoxin to the culture supernatant when expressed in E. coli. DNA sequence analysis showed the presence of two secretion genes, designated lktB and lktD in order of their genetic organization, which code for proteins of 79.7 and 54.7 kilodaltons, both of which were detected when pLKT52 was expressed in E. coli minicells. The lktB and lktD genes were found to be highly homologous to the hlyB and hlyD secretion genes of the hemolysin determinant, and the predicted LktB-HlyB and LktD-HlyD proteins were 90.5 and 75.6% homologous. Nucleotide sequence homology between the leukotoxin and hemolysin determinants was limited to the C, A, B, and D coding regions, although the presence of similar transcriptional terminators in the A-B intercistronic region is suggestive of a similar transcriptional organization. On the basis of these data, we hypothesize that the two determinants share a common evolutionary history and are prototypes for a widely disseminated family of virulence factors, the RTX cytotoxins. PMID- 2914878 TI - Increase of ornithine amino lipid content in a sulfonolipid-deficient mutant of Cytophaga johnsonae. AB - The gram-negative gliding bacterium Cytophaga johnsonae contains not only large quantities of unusual sulfonolipids but also, as we report here, a second class of unusual lipids. These lipids were detected and quantified by two-dimensional thin-layer chromatography of lipids from cells grown in the presence of [14C]acetate and shown by chemical studies to be alpha-N-(3-fatty acyloxy fatty acyl)ornithines. Like the sulfonolipids, these ornithine lipids were localized in the outer membrane (whereas phosphatidylethanolamine was the predominant lipid of the inner membrane). In a sulfonolipid-deficient mutant, the missing lipid was replaced, specifically, by an increased amount of ornithine lipid. Cells grown in liquid media contained predominantly ornithine lipids with nonhydroxylated residues in the O-fatty acyl position. In contrast, surface-grown cells contained a high proportion of ornithine lipids in which the O-fatty acyl group was 3 hydroxylated. The sulfonolipids and ornithine lipids are apparently coregulated in the sense that, regardless of perturbations caused by mutation or growth conditions, their total amounts remain constant at 40% of total cell lipid. PMID- 2914877 TI - Biosynthesis of linkage units for teichoic acids in gram-positive bacteria: distribution of related enzymes and their specificities for UDP-sugars and lipid linked intermediates. AB - The distribution and substrate specificities of enzymes involved in the formation of linkage units which contain N-acetylglucosamine (GlcNAc) and N acetylmannosamine (ManNAc) or glucose and join teichoic acid chains to peptidoglycan were studied among membrane systems obtained from the following two groups of gram-positive bacteria: group A, including Bacillus subtilis, Bacillus licheniformis, Bacillus pumilus, Staphylococcus aureus, and Lactobacillus plantarum; group B, Bacillus coagulans. All the membrane preparations tested catalyzed the synthesis of N-acetylglucosaminyl pyrophosphorylpolyprenol (GlcNAc PP-polyprenol). The enzymes transferring glycosyl residues to GlcNAc-PP polyprenol were specific to either UDP-ManNAc (group A strains) or UDP-glucose (group B strains). In the synthesis of the disaccharide-bound lipids, GlcNAc-PP dolichol could substitute for GlcNAc-PP-undecaprenol. ManNAc-GlcNAc-PP undecaprenol, ManNAc-GlcNAc-PP-dolichol, Glc-GlcNAc-PP-undecaprenol, Glc-GlcNAc PP-dolichol, and GlcNAc-GlcNAc-PP-undecaprenol were more or less efficiently converted to glycerol phosphate-containing lipid intermediates and polymers in the membrane systems of B. subtilis W23 and B. coagulans AHU 1366. However, GlcNAc-GlcNAc-PP-dolichol could not serve as an intermediate in either of these membrane systems. Further studies on the exchangeability of ManNAc-GlcNAc-PP undecaprenol and Glc-GlcNAc-PP-undecaprenol revealed that in the membrane systems of S. aureus strains and other B. coagulans strains both disaccharide-inked lipids served almost equally as intermediates in the synthesis of polymers. In the membrane systems of other B. subtilis strains as well as B. licheniformis and B. pumilus strains, however, the replacement of ManNAc-GlcNAc-PP-undecaprenol by Glc-GlcNAc-PP-undecaprenol led to a great accumulation of (glycerol phosphate) Glc-GlcNAc-PP-undecaprenol accompanied by a decrease in the formation of polymers. PMID- 2914879 TI - Two highly related insecticidal crystal proteins of Bacillus thuringiensis subsp. kurstaki possess different host range specificities. AB - Two genes encoding insecticidal crystal proteins from Bacillus thuringiensis subsp. kurstaki HD-1 were cloned and sequenced. Both genes, designated cryB1 and cryB2, encode polypeptides of 633 amino acids having a molecular mass of ca. 71 kilodaltons (kDa). Despite the fact that these two proteins display 87% identity in amino acid sequence, they exhibit different toxin specificities. The cryB1 gene product is toxic to both dipteran (Aedes aegypti) and lepidopteran (Manduca sexta) larvae, whereas the cryB2 gene product is toxic only to the latter. DNA sequence analysis indicates that cryB1 is the distal gene of an operon which is comprised of three open reading frames (designated orf1, orf2, and cryB1). The proteins encoded by cryB1 and orf2 are components of small cuboidal crystals found in several subspecies and strains of B. thuringiensis; it is not known whether the orf1 or cryB2 gene products are present in cuboidal crystals. The protein encoded by orf2 has an electrophoretic mobility corresponding to a molecular mass of ca. 50 kDa, although the gene has a coding capacity for a polypeptide of ca. 29 kDa. Examination of the deduced amino acid sequence for this protein reveals an unusual structure which may account for its aberrant electrophoretic mobility: it contains a 15-amino-acid motif repeated 11 times in tandem. Escherichia coli extracts prepared from cells expressing only orf1 and orf2 are not toxic to either test insect. PMID- 2914881 TI - Comorbidity of bulimia nervosa and personality disorder. AB - Thirty patients meeting DSM-III-R criteria for bulimia nervosa with at least three bingeing episodes a week were compared with 30 age- and sex-matched controls on DSM-III personality measures. The bulimic patients were more likely to display cluster B (histrionic, narcissistic, antisocial, and borderline) personality abnormalities (odds ratio 15.0) and cluster C (avoidant, dependent, compulsive, and passive-aggressive) personality abnormalities (odds ratio 4.3) than were the community controls. This study supports the finding that personality disorder is a possible risk factor for bulimia. PMID- 2914880 TI - Effect of degradative plasmid CAM-OCT on responses of Pseudomonas bacteria to UV light. AB - The effect of plasmid CAM-OCT on responses to UV irradiation was compared in Pseudomonas aeruginosa, in Pseudomonas putida, and in Pseudomonas putida mutants carrying mutations in UV response genes. CAM-OCT substantially increased both survival and mutagenesis in the two species. P. aeruginosa strains without CAM OCT exhibited much higher UV sensitivity than did P. putida strains. UV-induced mutagenesis of plasmid-free P. putida was easily detected in three different assays (two reversion assays and one forward mutation assay), whereas UV mutagenesis of P. aeruginosa without CAM-OCT was seen only in the forward mutation assay. These results suggest major differences in DNA repair between the two species and highlight the presence of error-prone repair functions on CAM OCT. A number of P. putida mutants carrying chromosomal mutations affecting either survival or mutagenesis after UV irradiation were isolated, and the effect of CAM-OCT on these mutants was determined. All mutations producing a UV sensitive phenotype in P. putida were fully suppressed by the plasmid, whereas the plasmid had a more variable effect on mutagenesis mutations, suppressing some and producing no suppression of others. On the basis of the results reported here and results obtained by others with plasmids carrying UV response genes, it appears that CAM-OCT may differ either in regulation or in the number and functions of UV response genes encoded. PMID- 2914882 TI - Hallervorden-Spatz disease in a psychiatric setting. AB - Neurodegenerative disorders of sufficient severity to be lethal are also likely to generate psychiatric symptomatology. At times, behavioral changes may predate neurologic manifestations, whereas at other times disturbances in mental status and physical functioning may coexist. In either situation, accurate assessment and appropriate treatment may prove challenging. The case of Hallervorden-Spatz disease reported here illustrates this difficulty; the authors present it to highlight the general issues that often arise in this group of illnesses. In this patient, as well as in three of his relatives, initially subtle neurologic signs were preceded by and then intermingled with significant and sometimes severe symptoms of depression. The authors emphasize the importance of attending to the neurologic symptom picture and family history in order to more appropriately assess the psychiatric manifestations of the disorder. Knowledge of neurodegenerative illnesses, even those as admittedly rare as Hallervorden-Spatz disease, can facilitate accurate and prompt diagnostic assessment, guide treatment strategies (including avoidance of inappropriate interventions), and help to more realistically define outcome expectations. PMID- 2914883 TI - Capgras' syndrome following minor head trauma. AB - Capgras' syndrome, the delusion of substitution, has been reported in the setting of many different underlying functional and organic conditions. Only two cases of the syndrome following major head trauma have been reported. The authors present the first reported case of Capgras' syndrome following minor head trauma in an elderly woman. PMID- 2914884 TI - Jitteriness and panic disorder. PMID- 2914885 TI - Munchausen syndrome: new cause for concern. PMID- 2914886 TI - Human plasminogen kringle 4. Crystallization and preliminary diffraction data of two different crystal forms. AB - Human plasminogen kringle 4 has been crystallized in two different crystal forms: monoclinic, a = 32.78(3), b = 49.17(2), c = 46.27(3) A, beta = 100.67 degrees, space group P2(1), four molecules/unit cell, two molecules/asymmetric unit; orthorhombic, a = 32.09(7), b = 49.14(6), c = 49.47(9) A, space group P2(1)2(1)2, four molecules/unit cell. Both crystal forms have a large protein fraction (66% for monoclinic and 62% for orthorhombic) and diffract x-rays to 2.0 A resolution. A self-rotation function has been calculated with monoclinic data indicating a non-crystallographic 2-fold rotation approximately parallel to a* (peak height of 14.3 x sigma). Cross-rotation function calculations are in progress utilizing the coordinates of the conserved structure of kringle 1 of prothrombin and plasminogen kringle 4. PMID- 2914887 TI - The effects of high pressure upon ligated and deoxyhemoglobins and myoglobin. An optical spectroscopic study. AB - The effects of high pressure (0.1-3.4 gigapascal (GPa)) on the ferrous heme active sites of human adult hemoglobin, sperm whale myoglobin, and Glycera dibranchiata hemoglobin (Fraction II) were probed using resonance Raman and absorption spectroscopies. High-to-low spin transitions of the heme iron occur for hemoglobin, myoglobin, and Glycera hemoglobin at 0.35, 0.75, and 0.50 GPa, respectively, for the deoxy species. These interspecies differences result from variations in the composition of the hemepockets and/or their rigidity to pressure-induced volume changes. Heme active sites initially bound to CO or O2 exhibit distinctive behavior at high pressures. For all proteins studied, O2 apparently dissociates from the heme at only moderately high pressure, while CO remains bound to the heme moiety even at extreme pressures. The Raman spectra demonstrate the differences in the ligated and deoxy species at 3.4 GPa in the high frequency region. Discrete changes (i.e. iron spin-state transitions and dissociation of O2) occur that are commensurate with the collapse of the distal pocket, while continuous shifts in the absorption and Raman spectra are observed at pressures above those required for pocket collapse. PMID- 2914888 TI - Human plasma lecithin-cholesterol acyltransferase. Inhibition of the phospholipase A2-like activity by sn-2-difluoroketone phosphatidylcholine analogues. AB - Lecithin-cholesterol acyltransferase (LCAT) is a plasma enzyme which catalyzes the transacylation of the sn-2-fatty acid of lecithin to cholesterol, forming lysolecithin and cholesteryl ester. We have recently proposed a covalent catalytic mechanism for LCAT in which lecithin cleavage proceeds via the formation of a transition state tetrahedral adduct between the oxygen atom of the catalytic serine residue and the sn-2-carbonyl carbon atom of the substrate (Jauhiainen, M., Ridgway, N.D., and Dolphin, P.J. (1987) Biochim. Biophys. Acta 918, 175-188). This proposal is evaluated here by use of nonhydrolyzable sn-2 difluoroketone phosphatidylcholine analogues, known to inhibit calcium-dependent phospholipase A2. These compounds inhibited the calcium-independent phospholipase A2 activity of LCAT in a time and concentration dependent manner. The most potent analogues had a 100-fold higher affinity for the enzyme than the substrate, lecithin, when present within lecithin/apoA-I proteoliposomes. The inhibition was dependent upon the presence of a difluoromethylene group alpha to the sn-2 carbonyl carbon of the analogues. The inhibition is attributed to the formation of a tetrahedral adduct between the catalytic serine residue of LCAT and the sn-2 carbonyl carbon atom of the analogues which is stabilized by the electronegative fluorine atoms present upon the carbon atom alpha to the carbonyl carbon. This adduct mimics that proposed by us to occur during lecithin cleavage by LCAT, and the data substantiate the existence of this transition state adduct prior to the release of lysolecithin and formation of a fatty acylserine oxyester of the enzyme. PMID- 2914889 TI - Purification and characterization of the epitectin from human laryngeal carcinoma cells. AB - The purification and partial characterization of epitectin (previously called Ca antigen) from a human cancer cell line is described. This glycoprotein, which is expressed on a wide range of human tumors and certain specialized normal epithelia, can be detected using monoclonal antibodies, Ca1, Ca2, and Ca3. The purified glycoprotein had a high density (1.40 g/ml) on isopycnic centrifugation indicating a high carbohydrate content. The molecular mass of epitectin as determined by size-exclusion chromatography ranged from 1.0 to 1.5 x 10(6) daltons. However, the purified epitectin gave two bands of apparent molecular weight 390,000 and 350,000 on polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The isoelectric points of epitectin and asialoepitectin were found to be 5.3-5.4 and 6.8, respectively. The oligosaccharides were isolated from metabolically labeled epitectin by alkaline borohydride treatment and their structures established based on high performance liquid chromatography and paper electrophoretic migration, sugar composition, the results of sequential exoglycosidase treatment, periodate oxidation, and methylation analysis. The structures of the three major fractions, which together account for about 80% of the radioactivity, were assigned as NeuNAc alpha 2--- 3Gal beta 1----(NeuNAc alpha 2----6)3GalNAc(OH), NeuNAc alpha 2----3Gal beta 1--- 3GalNAc(OH), and Gal beta 1----3 GalNAc(OH). The structures of the minor fractions were tentatively assigned as NeuNAc----Gal(NeuNAc----Gal----GlcNAc)--- GalNAc(OH), Gal beta 1----(NeuNAc alpha 2----6)3GalNAc(OH), NeuNAc alpha 2--- 6GalNAc(OH), and GalNAc(OH). It is proposed that the protein sequence and/or the distribution of the saccharides on the protein core are the determinants on epitectin that are recognized by the Ca antibodies. PMID- 2914890 TI - Oxidation of cycloalkylamines by cytochrome P-450. Mechanism-based inactivation, adduct formation, ring expansion, and nitrone formation. AB - Mechanism-based destruction of cytochrome P-450 (P-450) and P-450 heme is observed during the oxidation of N-cyclopropyl and N-cyclobutyl benzylamines. The slower inactivation by the cyclobutylamines relative to cyclopropylamines is consistent with known relative rates of ring opening of cycloalkyl-substituted aminium radicals. Evidence was found that porphyrin meso adducts of the type reported for horseradish peroxidase and cyclopropanone hydrate (Wiseman, J. S., Nichols, J. S., and Kolpak, M. X. (1982) J. Biol. Chem. 257, 6328-6332) were not formed. Radiolabels from cyclopropylamine substrates were covalently attached to protein but essentially only from the cyclopropyl portion and not the benzylic portion. Neither label appeared to be bound to extractable heme; however, during oxidations with cyclopropylamines, labeled P-450 heme became covalently attached to protein. Oxidation of 1-phenylcyclobutylamine by P-450 yielded 2-phenyl-1 pyrroline and 2-phenylpyrrolidine, and the ring expansion is interpreted as evidence for the existence of aminium radicals based on precedents with monoamine oxidase (Silverman, R. B., and Zieske, P. A. (1985) Biochemistry 24, 2128-2138). In addition, purified P-450PB-B oxidized N-(1-phenylcyclobutyl)-benzylamine to N (1-phenyl)cyclobutyl phenyl nitrone, identified using spectral techniques. This transformation involves two sequential oxidations with either a hydroxylamine or benzylidene intermediate. While P-450 oxidized the amine to both compounds, only the hydroxylamine was rapidly oxidized to give the nitrone. The ring expansion and nitrone products are interpreted in the context of aminium radical intermediates involved in the mechanism of P-450-catalyzed amine oxidation. PMID- 2914891 TI - A proton and fluorine-19 nuclear magnetic resonance and fluorescence study of the binding of some natural and synthetic thyromimetics to prealbumin (transthyretin). AB - Interactions between prealbumin and several thyromimetic compounds have been examined by proton magnetic resonance spectroscopy. One equivalent of thyroxine (T4) or reverse triiodothyronine (rT3) selectively broadens a number of protein signals, while addition of a second equivalent induces much less widespread changes. One equivalent of triiodothyronine (T3), however, produces much less dramatic changes, and effects comparable with T4 and rT3 are only apparent when a second equivalent binds. The broadening is ascribed to immobilization of flexible residues. The non-halogenated analogue 3,5-dimethyl-3'-isopropylthyronine induces qualitatively different changes suggesting incomplete entry into the thyromimetic binding channel. The fluorinated analogue SK&F 95049 (3,5-bis-thiotrifluoromethyl 3'-isopropylthyronine) induces very similar changes to T3. A fluorine-19 NMR signal with a half-height line width of approximately 150 Hz can be observed from the bound ligand. Finally, a spin-labeled T4 analogue, with a nitroxyl on the alanyl moiety, induces changes identical to those induced by T4 itself, and additionally broadens some signals corresponding to residues at the opening of the ligand binding channel. The natural tryptophan fluorescence of the protein is shown to be a sensitive indicator of binding. The possible influence of the dynamic restrictions induced by binding the first molecule of T4 or rT3 on the protein's affinity for a second hormone is discussed. It is suggested that the first interaction confers rigidity on the second site and reduces its ability to flex open and accommodate a second thyromimetic, which results in the marked negative co-operativity associated with the occupancy of this site. PMID- 2914892 TI - Purification, characterization, and rapid inactivation of thermolabile ubiquitin activating enzyme from the mammalian cell cycle mutant ts85. AB - Conjugation of ubiquitin to certain proteins can trigger their degradation in the in vitro reticulocyte system. In order to determine whether ubiquitin conjugation serves as an intermediate step in the turnover of cellular proteins in vivo, it is necessary to isolate proteolytic intermediates, i.e. ubiquitin-protein adducts of specific cellular proteins. While the steady-state level of conjugates of rapidly turning over proteins is relatively high, that of long-lived proteins is presumably extremely low, and therefore undetectable. Therefore, mutant cell lines with conditionally altered function(s) of the ubiquitin system can serve as powerful tools in studying the degradation of stable cellular proteins. We have characterized a temperature sensitive cell cycle arrest mutant cell (ts85) with a thermolabile ubiquitin-activating enzyme (E1; Finley, D., Ciechanover, A., and Varshavsky, A. (1984) Cell 37, 43-55). Following incubation at the restrictive temperature (39.5 degrees C), these cells fail to degrade short-lived proteins (Ciechanover, A., Finley, D., and Varshavsky, A. (1984) Cell 37, 57-66). However, involvement of the ubiquitin system in the turnover of long-lived proteins has not been addressed in these cells. A slow rate of inactivation of E1 in vivo, and significant rate of cell death following long incubation periods at the restrictive temperature, make this question difficult to address experimentally. In the present study we show that incubation of the cells for 1 h at 43 degrees C leads to rapid inactivation of ubiquitin conjugation in the intact mutant cell. Following heat treatment, the cells can be incubated at 39.5 degrees C for at least 6 h in order to study the possible involvement of the system in the turnover of long-lived cellular proteins. The viability of the cells is excellent at the end of the incubation. Following extraction, we have shown that inactivation occurs much more rapidly in the cell lysate in vitro than in the intact cell (t1/2 of 10 min compared to 4 h at 39.5 degrees C). The enzyme from both the mutant cell and the wild-type cell was purified to homogeneity. The molecular mass of the native enzyme from both cells is approximately 220 kDa with a subunit molecular mass of about 108 kDa. The structure of the enzyme is therefore very similar to that purified from rabbit reticulocytes. At the permissive temperature, the enzymes from both cells catalyze ATP-PPi and ATP-AMP exchange in similar kinetics. However, at the high temperature, the mutated enzyme is at least 7-fold less stable than the wild-type enzyme.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2914893 TI - Molecular cloning sequence and distribution of rat calspermin, a high affinity calmodulin-binding protein. AB - Calspermin is a heat-stable, acidic calmodulin-binding protein predominantly found in mammalian testis. The cDNA representing the rat form of this protein has been cloned from a rat testis lambda gt11 library. Sequence analysis of two overlapping clones revealed a 232-nucleotide 5'-nontranslated region, 510 nucleotides of open reading frame, a 148-nucleotide 3'-untranslated region, and a poly(A) tail. Authenticity of the clones was confirmed by comparison of a portion of the deduced amino acid sequence with the sequence of a tryptic peptide obtained from the rat testis protein. The lambda gt11 fusion protein was recognized by affinity purified antibodies to pig testis calspermin and bound 125I-calmodulin in a Ca2+-dependent manner. Calspermin cDNA encodes a 169-residue protein with a calculated Mr of 18,735. The putative calmodulin-binding domain is very close to the amino terminus of the protein. This region shows 46% identity with the calmodulin-binding region of rat brain Ca2+/calmodulin-dependent protein kinase II and 32% identity with the equivalent region of chicken smooth muscle myosin light chain kinase. The 5'-nontranslated region reveals significant homology with a portion of the catalytic region of the calmodulin-dependent protein kinase family. Calspermin contains a stretch of 17 contiguous glutamic acid residues in the central region of the molecule. Computer analysis predicts calspermin to be 81% alpha-helix and 14% random coil. Analysis of genomic DNA indicates calspermin to be the product of a unique gene. Northern blot analysis of rat testis RNA reveals a 1.1-kilobase mRNA. This RNA is restricted to testis among several rat tissues examined and could not be identified in total RNA isolated from testes of other mammals. Analysis of cells isolated from rat testis reveals calspermin mRNA to be predominantly expressed in postmeiotic cells indicating that it may be specific to haploid cells. PMID- 2914894 TI - The three-dimensional structure of bovine platelet factor 4 at 3.0-A resolution. AB - Platelet factor 4 (PF4), which is released by platelets during coagulation, binds very tightly to negatively charged oligosaccharides such as heparin. To date, six other proteins are known that are homologous in sequence with PF4 but have quite different functions. The structure of a tetramer of bovine PF4 complexed with one Ni(CN)4(2-) molecule has been determined at 3.0 A resolution and refined to an R factor of 0.28. The current model contains residues 24-85, no solvent, and one overall temperature factor. Residues 1-13, which carried an oligosaccharide chain, were removed with elastase to induce crystallization; residues 14-23 and presumably 86-88 are disordered in the electron density map. Because no heavy atom derivative was isomorphous with the native crystals, the complex of PF4 with one Ni(CN)4(2-) molecule was solved using a single, highly isomorphous Pt(CN)4(2 ) derivative and the iterative, single isomorphous replacement method. The secondary structure of the PF4 subunit, from amino- to carboxyl-terminal end, consists of an extended loop, three strands of antiparallel beta-sheet arranged in a Greek key, and one alpha-helix. The tetramer contains two extended, six stranded beta-sheets, each formed by two subunits, which are arranged back-to back to form a "beta-bilayer" structure with two buried salt bridges sandwiched in the middle. The carboxyl-terminal alpha-helices, which contain lysine residues that are thought to be intimately involved in binding heparin, are arranged as antiparallel pairs on the surface of each extended beta-sheet. PMID- 2914895 TI - Identification of methyl resonances in the 1H NMR spectrum of incubated blood cell lysates. AB - The origin of low frequency methyl resonances which appear in the spin-echo 1H nuclear magnetic resonance spectra of incubated blood cell lysates was investigated by several techniques including 1H and 13C nuclear magnetic resonance spectroscopy, electrophoresis, high performance liquid chromatography, gel filtration, and amino acid analysis. These resonances were identified as arising from methyl moieties of leucine and valine. Other peaks which also appeared in the spectra of incubated blood cell lysates were assigned to methyl groups of alanine and threonine. The free amino acids are products of neutral proteases located on the leukocyte membrane or able to act on the extracellular medium. Since more than one enzyme appears to be implicated, it is possible that both membrane and granule proteases take part in the hydrolysis. Comparison of rates of product formation in white cell lysates incubated with human serum albumin, and with red cell lysate, suggests that erythrocyte peptidases also contribute to proteolysis in the latter case. PMID- 2914896 TI - Interaction of a positive regulatory factor(s) with a 106-base pair upstream region controls transcription of metallothionein-I gene in the liver. AB - The differential transcription of the cloned mouse metallothionein-I (MT-I) gene in tissues was studied in unfractionated and fractionated nuclear extracts from rat liver and brain. MT-I gene transcription was 10-fold greater in liver nuclear extract than in brain nuclear extract, whereas the level of transcription of the histone H4 gene was almost identical in both tissue extracts. 5' Deletion analysis of upstream sequences revealed that a 106-base pair (bp) region located between the -148- and -42-bp positions with respect to the transcription start site was responsible for the higher level of expression of the MT-I gene in the liver. Preincubation of the liver extract with the 106-bp fragment resulted in a significant decrease in MT-I gene transcription in the liver extract. In contrast, MT-I gene transcription in the brain nuclear extract was not altered by preincubation with the 106-bp upstream sequence. Mixing liver and brain extract did not diminish MT-I gene transcription normally occurring in liver nuclear extract. Preincubation of brain nuclear extract with the MT-I gene had no inhibitory effect on transcription of MT-I gene in liver nuclear extract. These studies suggest that neither an inhibitor nor a negative trans-acting factor in the brain is responsible for the differential transcription of MT-I gene; rather a positive regulatory factor(s) in the liver which interacts with the 106-bp upstream region contributes to the higher level of MT-I gene expression in this tissue. PMID- 2914897 TI - On the origin of the positive band in the far-ultraviolet circular dichroic spectrum of fibronectin. AB - The genesis of the positive bands in the far-ultraviolet circular dichroic spectra of human plasma fibronectin and its 31-kDa NH2-terminal heparin-binding fragment was studied. Spectra of ester derivatives of tyrosine, tryptophan, and phenylalanine and of model mixtures of these derivatives in which they are present in the same ratios as in the proteins indicate that all the aromatic side chains make substantial contributions to composite positive bands with maxima several nanometers below those of the proteins. In the presence of solvent perturbants such as polyethylene glycol and ethylene glycol, the bands of the model mixtures are red-shifted to the approximate positions they have in the spectra of the proteins. No additional red shift is seen with solvent perturbation of the proteins, suggesting that the conditions leading to this effect are satisfied within the proteins. A separate effect of solvent perturbation, an increase in amplitude of the positive band, occurs equally in solutions of free aromatic amino acid derivatives and in the proteins. This effect is used to estimate the relative accessibility of the chromophores of fibronectin and its fragment to different perturbants. The possible influence of protein secondary structure on the amplitude of the positive circular dichroic band is discussed. PMID- 2914898 TI - Purification and characterization of two classes of neurotoxins from the funnel web spider, Agelenopsis aperta. AB - Two classes of paralytic toxins were isolated from the venom of Agelenopsis aperta and their chemical and larvicidal properties characterized. Five acylpolyamine toxins (alpha-agatoxins) of molecular masses 452, 488, 489, 504, and 505 Da produce immediate but reversible paralysis in Manduca sexta following injection. Six insecticidal peptides (mu-agatoxins) produce a gradual but irreversible paralysis. The complete amino acid sequences (36-38 residues) of the mu-agatoxins are presented. These peptides contain eight half-cystines and are quite similar in sequence. At least four of these toxins are amidated at the carboxyl terminus. The secondary structure of one of these toxins (mu-Aga V) was investigated. PMID- 2914899 TI - Histone H1 binds to the putative nuclear factor I recognition sequence in the mouse alpha 2(I) collagen promoter. AB - It has previously been demonstrated that nuclear factor I (NF I) or a related protein binds to a region between -315 and -295 from the start of transcription in the mouse alpha 2(I) collagen gene promoter. In the present work we have purified this factor to homogeneity from rat liver. DNA sequence-specific proteins were isolated from nuclear extracts using heparin-agarose affinity chromatography and two successive chromatographies on a recognition site affinity matrix. Approximately 160 micrograms of the DNA binding proteins was obtained from 100 g of rat liver. More than 1700-fold purification over the nuclear extract and 58% recovery of the DNA binding activity was achieved. The purified preparation contained five to six protein components ranging in molecular weight from 30,000 to 35,000, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. It was demonstrated using DNase I footprint analysis that the factor binds to the putative NF I binding site in the mouse alpha 2(I) collagen promoter. It has a dissociation constant of 7 nM for a short DNA fragment containing this binding site, while a constant of 0.45 nM was obtained for a similar-sized fragment containing the nuclear NF I consensus binding sequence. The purified factor is identical to histone H1 in several respects. They share similar amino acid compositions and they give similar V8-protease and N bromosuccinimide peptides. In addition, antibodies raised to bovine histone H1 recognize the purified factor and interfere with its binding to DNA. Methylation interference and preparative gel shift assay show that histone H1 binds to the specific sequence from the preparation of the alpha 2(I) collagen promoter binding factor. It is thus evident from the present results, that histone H1 binds to the NF I recognition sequence in the mouse alpha 2(I) collagen promoter. PMID- 2914900 TI - Evidence for an imipramine-sensitive serotonin transporter in human placental brush-border membranes. AB - Serotonin is actively transported into brush-border membrane vesicles isolated from normal human term placentas and an inward-directed NaCl gradient provides the driving force for this process. Uptake is negligible if Na+ is replaced by Li+, K+, Rb+, Cs+ or choline. The presence of Cl- seems necessary for the maximal activity of this Na+-dependent uptake system. Intravesicular K+ (20-40 mM) stimulates serotonin uptake, the stimulation being considerably greater at pH 7.5 than at pH 6.5. But, in the absence of K+, uptake at pH 6.5 was twice the uptake at pH 7.5. Unlabeled serotonin and dopamine inhibit the uptake of radiolabeled serotonin and the IC50 values are 70 nM and 20 microM, respectively. Histamine and 5-hydroxytryptophan do not significantly interact with the system (IC50 greater than 1 mM). Kinetic analysis reveals that serotonin uptake in these vesicles occurs via a single, saturable, high affinity system (Kt = 51 +/- 2 nM; Vmax = 6.4 +/- 0.1 pmol/mg of protein/15 s). The transporter is highly sensitive to inhibition by imipramine (IC50 = 32 nM) and desipramine (IC50 = 160 nM) but relatively insensitive to reserpine and hydralazine. PMID- 2914901 TI - Mammalian progesterone receptor shows differential sensitivity to sulfhydryl group modifying agents when bound to agonist and antagonist ligands. AB - Modulation of calf uterine progesterone receptor (PR), in relation to its binding to synthetic steroids with known agonist (R5020) and antagonist (RU486) properties, was studied in the presence of iodoacetamide (IA), N-ethylmaleimide (NEM), beta-mercaptoethanol (MER), and dithiothreitol (DTT). Pretreatment of uterine cytosol at 4 degrees C with NEM (4-10 mM) reduced the binding of [3H]RU486 to PR by 40%, but [3H] R5020 binding was completely abolished. Whereas IA (2-10 mM) treatment did not affect [3H]RU486 binding, [3H]R5020 binding was totally eliminated. DTT or MER increased the binding of both steroids slightly (15%). [3H]R5020- or [3H]RU486-receptor complexes (Rc) migrated in the 8 S region and were eliminated upon pretreatment with NEM. At 23 degrees C, DTT increased the amount of 4 S [3H]R5020-Rc, but had no effect on the [3H]RU486-Rc. In the control, [3H]RU486 binding to the 8 S PR could be competed with radioinert R5020 or RU486, but R5020 failed to compete in the presence of IA. The heat-treated [3H]R5020- and [3H]RU486-Rc showed reduced binding to DNA-cellulose in the presence of NEM and IA. The results of our study suggest that SH group modifications differentially influence the properties of mammalian PR complexed with either R5020 or RU486. In the presence of IA, the [3H]RU486-Rc remained in the 8 S form when incubated at 23 degrees C, indicating that RU486 binding causes conformational changes in PR which are distinct from those that result upon R5020 binding. PMID- 2914902 TI - Acidification and ion permeabilities of highly purified rat liver endosomes. AB - While it is well established that acidic pH in endosomes plays a critical role in mediating the orderly traffic of receptors and ligands during endocytosis, little is known about the bioenergetics or regulation of endosome acidification. Using highly enriched fractions of rat liver endosomes prepared by free flow electrophoresis and sucrose density gradient centrifugation, we have analyzed the mechanism of ATP-dependent acidification and ion permeability properties of the endosomal membrane. This procedure permitted the isolation of endosome fractions which were up to 200-fold enriched as indicated by the increased specific activity of ATP-dependent proton transport. Acidification was monitored using hepatocyte and total liver endosomes selectively labeled with pH-sensitive markers of receptor-mediated endocytosis (fluorescein isothiocyanate asialoorosomucoid) or fluid-phase endocytosis (fluorescein isothiocyanate dextran). In addition, changes in membrane potential accompanying ATP-dependent acidification were directly measured using the voltage-sensitive fluorescent dye Di-S-C3(5). Our results indicate that ATP-dependent acidification of liver endosomes is electrogenic, with proton transport being accompanied by the generation of an interior-positive membrane potential opposing further acidification. The membrane potential can be dissipated by the influx of permeant external anions or efflux of internal alkali cations. Replacement externally of permeable anions with less permeable anions (e.g. replacing Cl- with gluconate) diminished acidification, as did replacement internally of a more permeant cation K+ with less permeant species (such as Na+ or tetramethylammonium). ATP-dependent H+ transport was not coupled to any specific anion or cation, however. The endosomal membrane was found to be extremely permeable to protons, with protons able to leak out almost as fast as they are pumped in. Thus, the internal pH of endosomes is likely to reflect a dynamic equilibrium of protons regulated by the intrinsic ion permeabilities of the endosomal membrane, in addition to the activity of an ATP-driven proton pump. PMID- 2914903 TI - Subunit associations in the mammalian pyruvate dehydrogenase complex. Structure and role of protein X and the pyruvate dehydrogenase component binding domain of the dihydrolipoyl transacetylase component. AB - We have further distinguished the structures and roles of the two lipoyl-bearing components of the pyruvate dehydrogenase complex, the dihydrolipoyl transacetylase (E2) component and the component designated as protein X. The amino acid sequences of the NH2-terminal regions of the lipoyl-bearing domain of the E2 component and protein X are different but related. The dihydrolipoyl dehydrogenase (E3) component but not the pyruvate dehydrogenase (E1) component protected protein X against proteolytic degradation by trypsin and protease Arg C. Protein X-specific polyclonal antibodies inhibit reconstitution of the overall reaction catalyzed by the complex (E2-X subcomplex recombined with the E1 and E3 components). The rate of development of this inhibition was reduced by pretreatment of E2-X subcomplex with the E3 component. These data strongly suggest the E3 component associates with protein X. The E1 component (an alpha 2 beta 2 tetramer), but not the E3 component, reduced trypsin cleavage of E2 subunits at 4 degrees C and altered the patterns of cleavage at 22 degrees C. At 22 degrees C a large (Mr congruent to 49,000) outer domain (E2LB) of the E2 component was produced. E2LB had the same NH2-terminal amino acid sequence as the smaller (Mr congruent to 38,000) lipoyl-bearing domain (E2L). E2LB, in contrast to E2L, interacted with both the E1 component and the beta subunit of the E1 component. Thus the E1 component is bound through an E1-binding domain that is located in E2 subunits between the inner domain and the outer, lipoyl-bearing domain. PMID- 2914904 TI - Human carboxypeptidase M. Purification and characterization of a membrane-bound carboxypeptidase that cleaves peptide hormones. AB - A membrane-bound neutral carboxypeptidase B-like enzyme was solubilized from human placental microvilli with 3-[(3-cholamidopropyl)-dimethylammonio]-1 propanesulfonate (CHAPS) and purified to homogeneity by ion-exchange chromatography and affinity chromatography on arginine-Sepharose. It gave a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with an apparent Mr of 62,000 with or without reduction. The enzyme is a glycoprotein as shown by its high affinity for concanavalin A-Sepharose and reduction in mass to 47,600 daltons after chemical deglycosylation. It has a neutral pH optimum, is activated by CoCl2, and inhibited by o-phenanthroline, 2-mercaptomethyl-3 guanidinoethylthiopropanoic acid, or cadmium acetate, indicating it is a metallopeptidase. The enzyme cleaves arginine or lysine from the COOH terminus of synthetic peptides (e.g. Bz-Gly-Arg, Bz-Gly-Lys, Bz-Ala-Lys, dansyl-Ala-Arg, where Bz is benzoyl and dansyl is 5-dimethylaminonaphthalene-1-sulfonyl) as well as from several biologically active substrates: dynorphin A(1-13), Met5-Arg6 enkephalin (Km = 46 microM, kcat = 934 min-1), bradykinin (Km = 16 microM, kcat = 147 min-1), Met5-Lys6-enkephalin (Km = 375 microM, kcat = 663 min-1), and Leu5 Arg6-enkephalin (Km = 63 microM, kcat = 106 min-1). Although the enzyme shares some properties with other carboxypeptidase B-like enzymes, it is structurally, catalytically, and immunologically distinct from pancreatic carboxypeptidase A or B, human plasma carboxypeptidase N, and carboxypeptidase H ("enkephalin convertase"). To denote that the enzyme is membrane-bound, and to distinguish it from other known carboxypeptidases, we propose the name "carboxypeptidase M." Because of its localization on the plasma membrane and optimal activity at neutral pH, carboxypeptidase M could inactivate or modulate the activity of peptide hormones either before or after their interaction with plasma membrane receptors. PMID- 2914905 TI - 5,6-Dichloro-1-beta-D-ribofuranosylbenzimidazole inhibits transcription elongation by RNA polymerase II in vitro. AB - The purine nucleoside analog 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) is a selective inhibitor of transcription by RNA polymerase II. Although a wealth of in vivo studies have suggested that DRB inhibits transcription by enhancing the premature termination of elongating polymerase molecules, in vitro studies to date have been interpreted to suggest that DRB acts at the level of transcription initiation. We have analyzed the mechanism of DRB-mediated transcription inhibition in vitro both in HeLa whole cell extracts and in a partially purified transcription system. The results indicate that the extent to which DRB inhibits the synthesis of a RNA transcript is directly proportional to its length. For example, DRB was found to preferentially inhibit transcription in vitro of promoter-distal relative to promoter-proximal portions of the adenovirus major late transcription unit. A factor potentially involved in mediating this inhibitory effect is identified. We conclude that the mechanism of DRB inhibition of transcription in vivo and in vitro are similar. PMID- 2914906 TI - In situ phosphorylation of human platelet myosin heavy and light chains by protein kinase C. AB - Treatment of human platelets with 162 nM 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted in phosphorylation of a number of peptides, including myosin heavy chain and the 20-kDa myosin light chain. The site phosphorylated on the myosin heavy chain was localized by two-dimensional peptide mapping to a serine residue(s) in a single major tryptic phosphopeptide. This phosphopeptide co migrated with a tryptic peptide that was produced following in vitro phosphorylation of platelet myosin heavy chain using protein kinase C. The sites phosphorylated in the 20-kDa myosin light chain in intact cells were analyzed by two-dimensional mapping of tryptic peptides and found to correspond to Ser1 and Ser2 in the turkey gizzard myosin light chain. In vitro phosphorylation of purified human platelet myosin by protein kinase C showed that in addition to Ser1 and Ser2, a third site corresponding to Thr9 in turkey gizzard myosin light chain is also phosphorylated. The phosphorylatable myosin light chains from human platelets were found to consist of two major isoforms present in approximately equal amounts, but differing in their molecular weights and isoelectric points. A third, minor isoform was also visualized by two-dimensional gel electrophoresis. Following treatment with TPA, both the mono- and diphosphorylated forms of each isoform could be visualized, and the sites of phosphorylation were identified. The phosphate content rose from negligible amounts found prior to treatment with TPA to 1.2 mol of phosphate/mol of myosin light chain and 0.7 mol of phosphate/mol of myosin heavy chain following treatment. These results suggest that TPA mediates phosphorylation of both myosin light and heavy chains in intact platelets by activation of protein kinase C. PMID- 2914907 TI - Purification and characterization of early pregnancy factor from human pregnancy sera. AB - Early pregnancy factor (EPF) is a pregnancy-associated protein detected in the maternal serum by using the rosette inhibition assay and by evaluating the suppression of adoptive transfer of contact sensitivity. Because of its inhibitory effect on the functional reactivity of immunocompetent cells, EPF is thought to be involved in immunoregulation of the maternal immune system during early pregnancy. EPF was purified six million-fold from the serum of pregnant women between 5 and 12 weeks of gestation. The specific activity of purified EPF was approximately 8 x 10(8) units/mg. The purification scheme involved sequential DEAE-cellulose chromatography, S-Sepharose chromatography, concanavalin A Sepharose chromatography, heparin-Sepharose chromatography, Mono S fast protein liquid chromatography, and preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The purified protein has an apparent molecular weight of 21,500 as analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and 28,000 by gel permeation high pressure liquid chromatography. The isoelectric point of purified EPF moiety is 6.5. The biological activity was susceptible to the proteolytic enzyme trypsin, acidic pH conditions, organic solvents, and sodium dodecyl sulfate, but stable to heat treatment at 56 degrees C for 30 min and the reducing agent dithiothreitol. The biological and physicochemical properties of EPF appear to be distinct from other pregnancy-associated and immunoregulatory proteins. PMID- 2914908 TI - The binding of heparin to type IV collagen: domain specificity with identification of peptide sequences from the alpha 1(IV) and alpha 2(IV) which preferentially bind heparin. AB - Three distinctive heparin-binding sites were observed in type IV collagen by the use of rotary shadowing: in the NC1 domain and at distances 100 and 300 nm from the NC1 domain. Scatchard analysis indicated different affinities for these sites. Electron microscopic analysis of heparin-type IV collagen interaction with increasing salt concentrations showed the different affinities to be NC1 greater than 100 nm greater than 300 nm. The NC1 domain bound specifically to chondroitin/dermatan sulfate side chains as well. This binding was observed at the electron microscope and in solid-phase binding assays (where chondroitin sulfate could compete for the binding of [3H]heparin to NC1-coated substrata). The triple helix-rich, rod-like domain of type IV collagen did not bind to chondroitin/dermatan sulfate side chains. In solid-phase binding assays only heparin could compete for the binding of [3H]heparin to this domain. In order to more precisely map potential heparin-binding sites in type IV collagen, we chemically synthesized 17 arginine- and lysine-containing peptides from the alpha 1(IV) and alpha 2(IV) chains. Three peptides from the known sequence of the alpha 1(IV) and alpha 2(IV) chains were shown to specifically bind heparin: peptide Hep I (TAGSCLRKFSTM), from the alpha 1(NC1) chain, peptide Hep-II (LAGSCLARFSTM), a peptide corresponding to the same sequence in peptide Hep-I from the alpha 2 (NC1) chain, and peptide Hep-III (GEFYFDLRLKGDK) which contained an interruption of the triple helical sequence of the alpha 1(IV) chain at about 300 nm from the NC1 domain, were demonstrated to bind heparin in solid-phase binding assays and compete for the binding of [3H]heparin to type IV collagen-coated substrata. Therefore, each of these peptides may represent a potential heparin-binding site in type IV collagen. The mapping of the binding of heparin or related structures, such as heparan sulfate proteoglycan, to specific sequences of type IV collagen could help the understanding of several structural and functional properties of this basement membrane protein as well as interactions with other basement membrane and/or cell surface-associated macromolecules. PMID- 2914909 TI - Alternative splicing mechanism in a cytochrome P-450 (P-450PB-1) gene generates the two mRNAs coding for proteins of different functions. AB - Two mRNAs for P-450PB-1 and P-450PB-1(ps) are about 2 kilobase pairs long and have identical sequences with each other except for one short region of high variability (Kimura, H., Yoshioka, H., Sogawa, K., Sakai, Y., and Fujii-Kuriyama, Y. (1988) J. Biol. Chem. 263, 701-707). To clarify the origin of the short replacement block between the two mRNAs, we isolated several genomic clones containing relevant gene sequences. Sequence analysis of these genomic clones revealed that the two short segments specific for the two mRNAs are tandemly arranged in a genomic sequence and form exonic sequences equipped with AG and GT sequences on their 5' and 3' ends, respectively, and the putative consensus sequences for the lariat formation. The two short sequences lie between the two exonic sequences coding for the common part of the two mRNAs. Taken together with the structure of the related P-450(M-1) gene (Morishima, N., Yoshioka, H., Higashi, Y., Sogawa, K., and Fujii-Kuriyama, Y. (1987) Biochemistry 26, 8279 8285), all these results clearly demonstrate that the two mRNAs are generated from a single gene by alternative splicing at the eighth exons. The synthesis of the two mRNAs is regulated temporally in livers of male and female rats and brains of the female animals. One of the two mRNAs codes for a monooxygenase of P 450PB-1, and the other (P-450PB-1(ps) mRNA) lacks the sequence coding for the heme-binding site conserved among all species of P-450 molecules, and, therefore, it cannot function as a monooxygenase. The immunoblot analysis using an antibody specific for the 15-mer peptide uniquely encoded by P-450PB-1(ps) mRNA shows that the P-450PB-1(ps) peptide is synthesized at least in rat livers of both sexes in temporally regulated manners and is bound to the microsomal membranes. The function of this peptide remains to be seen. PMID- 2914910 TI - The human thymidine kinase gene promoter. Deletion analysis and specific protein binding. AB - We report a functional analysis of the human thymidine kinase (tk) gene promoter. We have linked the tk promoter to the chloramphenicol acetyltransferase (CAT) gene to allow direct measurement of promoter strength by assaying chloramphenicol acetyltransferase enzyme activity after transfection into mouse L cells. Putative transcription elements have been identified by deletion and mutation analysis of this promoter. The promoter relies primarily on two "CCAAT" elements and a series of "GC" elements found farther upstream. Two-thirds of promoter activity is maintained by a construct containing 139 base pairs of sequence upstream of the initiation of transcription that contains only one GC and one of the CCAAT elements. In addition, an evolutionary comparison identifies two highly conserved promoter elements: the -40 CCAAT element and a "TATA" element located at -21. We have further characterized both CCAAT elements using a mutational as well as protein binding analysis. From this study we have determined that both the -70 and -40 CCAAT elements bind strongly to the same factor, with a slightly higher affinity for the -40 CCAAT. Competition studies suggest that the CCAAT factor that binds to this promoter is homologous to protein nuclear factor Y, which binds to the major histocompatibility complex class II E alpha gene promoter. In addition, either CCAAT element is capable of supplying almost as much promoter strength as is supplied in the presence of both. PMID- 2914911 TI - A multisubunit transcription factor essential for accurate initiation by RNA polymerase II. AB - We have fractionated rat liver and identified a set of transcription factors that are essential for accurate initiation of transcription by RNA polymerase II. These factors were resolved into three distinct enzyme fractions. The factors in two of these fractions have been purified to apparent homogeneity. One fraction contains a single, 35-kDa transcription factor, designated alpha (Conaway, J. W., Bond, M. W., and Conaway, R. C. (1987) J. Biol. Chem. 262, 8293-8297). Here we show that the other fraction contains a transcription factor, designated beta gamma, with a native molecular mass of approximately 250 kDa. This factor is composed of 67 kDa (beta) and 31 kDa (gamma) polypeptides. Both the beta and gamma polypeptides are required for runoff transcription. Comparison of purified transcription factors alpha and beta gamma reveals that (i) both factors act at initiation and (ii) neither alpha nor beta gamma is required for assembly of an initial complex that commits the template to be transcribed by RNA polymerase II. PMID- 2914912 TI - Rat pyruvate kinase M gene. Its complete structure and characterization of the 5' flanking region. AB - Genomic clones containing the rat pyruvate kinase M gene, which encodes the M1- and M2-type isozymes, were isolated and their exon sequences were determined. This gene contains 12 exons and 11 introns and is 20 kilobases (kb) long. The sequences specific to the M1- and M2-types exist in exons 9 and 10, respectively (Noguchi, T., Inoue, H., and Tanaka, T. (1986) J. Biol. Chem. 261, 13807-13812). The seventh intron begins with the GC dinucleotide instead of the consensus GT dinucleotide, but other exon-intron boundaries are consistent with the "GT-AG" rule. S1 mapping analysis showed that M1- and M2-type mRNAs had multiple, but the same transcription initiation sites. Thus, the M1- and M2-type isozyme mRNAs are concluded to be produced from the same M gene transcript by alternative RNA splicing. RNA blot hybridization analysis indicated that developmental changes of the isozymes in brain and skeletal muscle were regulated at the level of RNA splicing. The 5'-flanking region of the gene has no "TATA box" or "CAAT box," but contains potential Sp1 binding sites. Bacterial chloramphenicol acetyltransferase assay revealed that a fragment of about 0.5 kb of the 5'-flanking region of the gene was sufficient for promotor activity in the rat hepatoma cell line, dRLh-84. This activity was not present in adult rat hepatocytes, indicating that the 0.5 kb fragment has tissue-specific promoter activity. A processed-type pseudogene that resembles the M2-type pyruvate kinase cDNA was also characterized. PMID- 2914913 TI - Biosynthesis and processing of the mannose receptor in human macrophages. AB - The biosynthesis and processing of the human mannose receptor has been studied in monocyte-derived macrophages. Adherent cells were labeled for 60 min with Trans35S (a mixture of 35S-labeled methionine and cysteine), chased, and subjected to immunoprecipitation by antibody raised against the human placental receptor. The antibody immunoprecipitated a single protein of molecular mass 162 kDa; precipitation of the labeled receptor could be inhibited by placental receptor. The results presented demonstrate that the receptor is synthesized as a 154-kDa precursor which is processed to 162 kDa in 90 min. The precursor is a glycoprotein bearing endoglycosidase H-sensitive oligosaccharides; the 162-kDa form is endoglycosidase H-resistant but peptide:N-glycanase-sensitive. Desialylation of the mannose receptor with neuraminidase generates a protein which is recognized by peanut agglutinin, a lectin that specifically binds desialylated O-linked oligosaccharides. Thus, the human macrophage mannose receptor bears both N- and O-linked oligosaccharide chains. Newly synthesized mannose receptor exhibits a half-life of 33 h as determined by pulse-chase studies. This indicates that on the average, each molecule of receptor recycles between the cell surface and endosomes hundreds of times before degradation. PMID- 2914914 TI - Subunit composition of the estrogen receptor. Involvement of the hormone-binding domain in the dimeric state. AB - The purified estrogen receptor (ER) whether in 9 or 5 S molecular form, binds more than one molecule of the monoclonal antibody JS 34/32 (Redeuilh, G., Moncharmont, B., Secco, C., and Baulieu, E.-E. (1987) J. Biol. Chem. 262, 6969 6975). We now have investigated the effects of controlled trypsin proteolysis and of a dissociating chaotropic salt (NaSCN) on the structure of the estrogen receptor covalently labeled with radioactive tamoxifen aziridine. When the DNA binding transformed 5S ER was dialyzed against a buffer containing 0.5 M NaSCN, it was converted into a form sedimenting at 3.7 S +/- 0.1 (n = 3). It reverted to the 5 S molecular form when NaSCN was dialyzed away. Fluorographic analysis of both the 5 and 3.7 S ER following SDS-gel electrophoresis revealed one main band corresponding to Mr congruent to 66,000. After limited trypsin treatment of the 5 S ER, tamoxifen aziridine-binding protein sedimented at 4.3 S +/- 0.1 (n = 5), had a Stokes radius of 3.6 nm (calculated Mr = 65,000), and did not bind DNA. The same form was obtained after limited trypsin digestion of the ER bound to DNA cellulose or to hsp 90 (the nontransformed 8-9 S ER molecular form). This 4.3 S trypsinized ER was reversibly dissociated by NaSCN into a congruent to 3 S +/- 0.1 (n = 3) molecular form. Fluorographic analysis of both the 4.3 and 3 S ER after SDS-gel electrophoresis showed one main radioactive band of Mr congruent to 30,000. Taken together our results suggest that 1) the 5 S ER is a homodimer of two Mr congruent to 66,000 hormone binding subunits which may be released as such from the nontransformed 8-9 S ER, 2) the trypsin digestion products yield two carboxyl-terminal fragments of Mr congruent to 30,000 that remain in the form of a dimer having lost their DNA-binding region, and 3) the trypsin cleavage would occur within the region located between the hormone-binding domain and the DNA binding domain. These data indicate that the dimerization of the receptor occurs through hydrophobic interaction of its hormone-binding domain but cannot exclude that other part(s) of the receptor may also contribute to the dimer formation. The dimerization may be critically involved in the mechanism by which estradiol receptor complexes promote change of gene transcription. PMID- 2914915 TI - Phorbol esters stimulate phosphorylation of eukaryotic initiation factors 3, 4B, and 4F. AB - Eukaryotic initiation factor (eIF) 4F, a multiprotein cap binding complex, was isolated by m7 GTP-Sepharose affinity chromatography from rabbit reticulocytes incubated with [32P]orthophosphate. Following treatment of reticulocytes with phorbol 12-myristate 13-acetate (PMA) for 30 min, stimulation of phosphorylation of both the p25 and p220 subunits was observed (2.5-5-fold). Two variants were observed for p25 in the absence and presence of PMA when analyzed by two dimensional gel electrophoresis. Only the more acidic of these was phosphorylated, with the level of phosphorylation increased upon PMA treatment. One main variant was observed for p220; following PMA stimulation, in addition to increased labeling of this variant, two more acidic phosphorylated variants were observed. Low levels of eIF-3 and -4B were associated with purified eIF-4F, and PMA treatment stimulated phosphorylation of eIF-3 (p170) by 2-4-fold and eIF-4B by 1.5-2.5 fold. Two-dimensional phosphopeptide mapping of p25 phosphorylated in the absence or presence of PMA generated a single tryptic phosphopeptide, suggesting a single phosphorylation site. A more complex phosphopeptide map was observed with p220 subunit. The maps for both subunits contained the same phosphopeptides as those obtained when eIF-4F was phosphorylated in vitro by the Ca2+/phospholipid-dependent protein kinase, indicating this protein kinase directly modulated eIF-4F in response to PMA. PMID- 2914916 TI - Thermostable D-amino acid aminotransferase from a thermophilic Bacillus species. Purification, characterization, and active site sequence determination. AB - D-Amino acid aminotransferase was found in several thermophilic Bacillus species and purified to homogeneity from the best producer, Bacillus sp. YM-1, which was newly isolated from a sauna dust. The enzyme has a molecular weight of about 62,000 and consists of two subunits identical in molecular weight (30,000). It catalyzes transamination between various D-amino acids and alpha-keto acids, although the substrate specificity is narrower than the enzyme from the mesophile, Bacillus sphaericus (Yonaha, K., Misono, H., Yamamoto, T., and Soda, K. (1975) J. Biol. Chem. 250, 6983-6989). The Bacillus sp. YM-1 enzyme is most active at 60 degrees C and stable at high temperatures. Automated Edman degradation provided the N-terminal sequence of the first 20 amino acids, and carboxypeptidase Y digestion provided the C-terminal sequence of the last 3 amino acids. The amino acid sequence in the vicinity of the lysyl residue, Lys(Pxy), that binds pyridoxal 5'-phosphate was determined as Cys-Asp-Ile-Lys(Pxy)-Ser-Leu Asn-Leu-Leu-Gly-Ala-Val-Leu-Ala-Lys- from the pyridoxyl peptide obtained by digestion with trypsin. The active site sequence is markedly different from those of L-amino acid aminotransferases and other pyridoxal 5'-phosphate-dependent enzymes. PMID- 2914917 TI - Reduced formation of bipyrimidine photoproducts in DNA UV irradiated at high intensity. AB - DNA was irradiated using an excimer laser (248 nm) at low intensity (3.15 x 10(7) watts/m2) or high intensity (1.25 x 10(11) watts/m2). Fluences up to 30 kJ/m2 were delivered at either intensity. Following irradiation, DNA damage products were measured, yielding the following findings: 1) the rate of formation of thymine-thymine and thymine-cytosine cyclobutane dimers and the bipyrimidine photoadduct 6-4'-[pyrimidine-2'-one]thymine were reduced at high intensity by about 2-fold and 2) extensive release of free thymine and thymine decomposition fragments occurred at high intensity, but not at low intensity. The effects of high intensity UV are due to promotion of low-lying excited state(s) by absorption of a second photon, producing higher excited state(s) with consequent ionization and base loss. Possible excited state intermediates in this process are the lowest triplet state of DNA bases and prolonged singlet states associated with excimer formation. The depletion of these excited states via promotion may be the cause of the diminished yield of bimolecular pyrimidine photoproducts, suggesting that these photoproducts are formed at low UV intensity in part from long-lived excited states. Long-lived excited states present at conventional UV intensities may contribute to formation of some photoproducts that occur rarely, but are of potential biologic importance, such as dimers between nonadjacent pyrimidines on the same strand and interstrand dimers forming DNA cross-links. PMID- 2914918 TI - L-pipecolic acid oxidation in the rabbit and cynomolgus monkey. Evidence for differing organellar locations and cofactor requirements in each species. AB - L-Pipecolic acid oxidation was studied in the rabbit and cynomolgus monkey. Tissue homogenates from both species incubated with L-[2,3,4,5,6-3H]pipecolic acid produced a single radioactive product identified as alpha-aminoadipic acid. In the rabbit, L-pipecolic acid oxidation was greatest in kidney cortex with progressively lesser specific activities in liver, heart, and brain. When rabbit kidney cortex was fractionated by differential centrifugation or on Percoll gradients, activity paralleled that of the mitochondrial marker, glutamate dehydrogenase. In sonicated mitochondria, 92% of the activity was in the soluble fraction. Activity was inhibited by both rotenone and antimycin A and was maximal when FAD, phenazine ethosulfate, and glycerol were included in the assay; Km,app was 0.74 +/- 0.16 mM. Nipecotic acid, piperidine, and cis-2,4-piperidine dicarboxylic acid did not inhibit L-pipecolic acid oxidation, while L-proline had a Ki greater than or equal to 10 mM. D-Alanine and kojic acid, substrate and inhibitor of D-amino acid oxidase, respectively, were also not inhibitory. When monkey kidney cortex was fractionated on Percoll gradients, L-pipecolic acid oxidation activity paralleled that of the peroxisomal marker, catalase. After organellar subfractionation, the activity was membrane-associated and maximal at pH 8.5; Km,app was 4.22 +/- 0.30 mM. L-Pipecolic acid oxidation produced hydrogen peroxide, suggesting involvement of an oxidase in alpha-aminoadipic acid formation. Antimycin A did not inhibit the reaction. No specific cofactor requirements were identified and phenazine ethosulfate inhibited the reaction. D Pipecolic acid, L-proline, and the other compounds cited above did not significantly inhibit the activity. PMID- 2914919 TI - The reactivity of chicken liver xanthine dehydrogenase with molecular oxygen. AB - The reaction of 6-electron reduced chicken liver xanthine dehydrogenase (XDH) with molecular oxygen was studied using both stopped flow and steady-state turnover techniques at pH 7.8, 4 degrees C. Oxidation of fully reduced XDH proceeded via four phases, three of which were detected with the stopped flow spectrophotometer. The fastest phase was second order in oxygen (1900 M-1 s-1), resulted in the appearance of flavin semiquinone and yielded no superoxide. The next phase was also second order in oxygen (260 M-1 s-1), involved the loss of flavin semiquinone and yielded, on average, 1 mol of superoxide/mol of XDH oxidized. The last 2 electron equivalents were located in the iron-sulfur centers. They were released one equivalent at a time in the form of superoxide. Steady-state kinetics were found to be critically dependent on temperature and oxygen concentration. When these factors were carefully controlled, both the xanthine-oxygen and NADH-oxygen reductase reactions gave linear Lineweaver-Burk plots. The xanthine-oxygen data yielded a turnover number of 43 min-1, which was 42% of that for xanthine-NAD turnover. During turnover, with xanthine and O2, 40 44% of the electron equivalents introduced by xanthine appeared as superoxide. Reduced pyridine nucleotides, NAD and 3-aminopyridine adenine dinucleotide, dramatically reduced the formation of superoxide at levels which did not seriously inhibit oxygen reactivity. PMID- 2914920 TI - The reactivity of plasma phospholipids with lecithin:cholesterol acyltransferase is decreased in fish oil-fed monkeys. AB - The size of low density lipoproteins (LDL) is strongly correlated with LDL cholesteryl ester (CE) content and coronary artery atherosclerosis in monkeys fed cholesterol and saturated fat. African green monkeys fed 11% (weight) fish oil diets have smaller LDL and less CE per LDL particle than lard-fed animals. We hypothesized that this might be due to a lower plasma lecithin:cholesterol acyltransferase (LCAT) activity in fish oil-fed animals. Using recombinant particles made of egg yolk lecithin-[14C]cholesterol-apoA-I as exogenous substrate, we found no difference in plasma LCAT activity (27 versus 28 nmol CE formed per h/ml) of fish oil- versus lard-fed animals, respectively; furthermore, no diet-induced difference in immunodetectable LCAT was found. However, plasma phospholipids from fish oil-fed animals were over 4-fold enriched in n-3 fatty acids in the sn-2 position compared to those of lard-fed animals. Additionally, the proportion of n-3 fatty acid-containing CE products formed by LCAT, relative to the available n-3 fatty acid in the sn-2 position of phospholipids, was less than one-tenth of that for linoleic acid. The overall rate of LCAT-catalyzed CE formation with phospholipid substrates from fish oil-fed animals was lower (5 50%) than with phospholipid substrates from lard-fed animals. These data show that n-3 fatty acids in phospholipids are not readily utilized by LCAT for formation of CE; rather, LCAT preferentially utilizes linoleic acid for CE formation. The amount of linoleic acid in the sn-2 position of plasma phospholipids is reduced and replaced with n-3 fatty acids in fish oil-fed animals. As a result, LCAT-catalyzed plasma CE formation in vivo is likely reduced in fish oil-fed animals contributing to the decreased cholesteryl ester content and smaller size of LDL particles in the animals of this diet group. PMID- 2914921 TI - Characterization of rat ovarian lutropin receptor. Role of thiol groups in receptor association. AB - Rat ovarian lutropin receptor occurs predominantly as a monomer of an apparent molecular mass of 70 or 80 kDa determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis under nonreducing and reducing conditions, respectively. The receptor contains 0.4% free cysteine and 1.9% cysteine as cystine, determined by amino acid analysis of the S-carboxymethyl receptor prepared before and after reduction. The presence of free thiol groups was further shown by the specific adsorption of the receptor on p chloromercuribenzoate-agarose and its susceptibility to 3H labeling with [3H]N ethylmaleimide or [3H]iodoacetic acid. The receptor readily undergoes association into homo-oligomers. Evidence suggests that the association was caused by the intermolecular oxidation of the free -SH groups to form disulfide bonds. The aggregation could be induced by H2O2 or molecular O2 and was inhibited by sulfhydryl protecting agents such as N-ethylmaleimide, iodoacetic acid, dithiothreitol, cysteine, and Zn(II). The oligomers could be dissociated by reduction into a monomer. 125I-Labeling of the S-carboxymethyl- or N-ethylmaleyl receptor gave a single band of molecular mass 70 kDa on sodium dodecyl sulfate polyacrylamide gel electrophoresis and autoradiography. Furthermore, S-alkylation of the receptor did not affect its binding to the ligand. On reduction, however, it lost its ability to bind to the ligand, but the reduced receptor retained its ability to bind to a specific polyclonal rabbit antireceptor antibody indicating the separation of the ligand and antibody binding sites. Endoproteinase Glu-C cleaved the receptor at a single glutamyl residue to give two components, 46 and 36 kDa. The 36-kDa component was extracellularly located since it contained the carbohydrate. On deglycosylation with endoglycosidase F, it yielded two components, 27 and 25 kDa. The deglycosylation of the reduced intact receptor (80 kDa) with endoglycosidase F occurred in two steps giving 73- and 64-kDa polypeptides, indicating the presence of about 20% carbohydrate contained in two or more N-linked chains. PMID- 2914922 TI - Chick heat-shock protein of Mr = 90,000, free or released from progesterone receptor, is in a dimeric form. AB - A monoclonal antibody (BF4) has been used to characterize and purify the heat shock protein of Mr approximately 90,000 (hsp 90) present in the chick oviduct. In low salt cytosol, the sedimentation coefficient of hsp 90 is approximately 6.8 S, the Stokes radius approximately 7.1 nm, and the calculated Mr approximately 204,000, thus suggesting a dimeric structure. In 0.4 M KCl cytosol, only slightly smaller values were determined (approximately 6.5 S, approximately 6.8 nm, and approximately 187,000). Following purification by ion exchange and immunoaffinity chromatography, hsp 90 migrated as a single silver-stained band at Mr approximately 90,000 in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, while the sedimentation coefficient 6.2 S, the Stokes radius approximately 6.8 nm, and the Mr approximately 178,000 confirmed the dimeric structure. However, in both antigen or antibody excess conditions, only one molecule of monoclonal antibody could be bound to the hsp 90 dimer. Whether steric hindrance in a homodimer or the presence of two different 90-kDa proteins in a heterodimer explains this result cannot yet be decided. The dimer is not dissociated by high salt (1 M KCl) or the chaotropic agent (0.5 M NaSCN), but is disrupted by 4 M urea, suggesting a stabilization of the structure by hydrogen bonds. The molybdate-stabilized progesterone receptor hetero-oligomer form of approximately 8 S sedimentation coefficient was purified, and its hsp 90 component was then released by salt treatment. It was found to sediment at approximately 5.8 S and have a Stokes radius approximately 7.1 nm, giving Mr approximately 174,000. This observation is consistent with a previous report suggesting from specific activity determination, scanning of polyacrylamide gels, and cross-linking experiments that each purified nontransformed progesterone receptor molecule includes one progesterone binding unit per two 90-kDa protein molecules (Renoir, J. M., Buchou, T., Mester, J., Radanyi, C., and Baulieu, E. E. (1984) Biochemistry 23, 6016-6023). This work brings direct evidence that both free hsp 90 and the non-hormone binding hsp 90 component released from the nontransformed steroid receptor in the cytosol are in a dimeric form. PMID- 2914923 TI - Rat liver mitochondrial and cytosolic fumarases with identical amino acid sequences are encoded from a single gene. AB - By use of anti-cytosolic fumarase antibody, a cDNA clone was isolated from a rat liver cDNA library in the expression vector lambda gt11 and in the pBR 322 vector. A clone with an insert of about 1.7 kilobases was isolated. Nucleotide sequence analysis of the insert revealed that the cDNA contained a 5'-noncoding region of 25 nucleotides, the coding region of 1,521 nucleotides, and a 3' nontranslated region of 43 nucleotides followed by a poly(A)+ tail. The open reading frame encoded a polypeptide of 507-amino acid residues (predicted Mr = 54,462), which contained an additional sequence of 41-amino acid residues on the NH2 terminus of the mitochondrial mature fumarase (the presequence). Thus, this reading frame was concluded to encode the precursor of mitochondrial fumarase. The amino acid sequence predicted from the nucleotide sequence contained all the amino acid sequences of 12 proteolytic polypeptides produced by digestion of purified mitochondrial fumarase with V8 protease. The total amino acid sequence of the mitochondrial fumarase also contained all the sequences of 14 proteolytic peptides obtained from the cytosolic fumarase, indicating that the amino acid sequences of these two isozymes are identical. Furthermore, the results obtained by hybrid-selected translation, Northern and Southern blot, and primer-extension analyses using appropriate cDNA segments prepared with fumarase cDNA (1.7 kilobases) as a probe or primer suggested that the mitochondrial and cytosolic fumarases with identical amino acid sequences are encoded from a single gene and a possibility that the precursors of both these fumarases were synthesized by one species of mRNA having a base sequence coding the presequence of the mitochondrial fumarase by some unknown post-transcriptional mechanism(s). PMID- 2914924 TI - A macrophage receptor that recognizes oxidized low density lipoprotein but not acetylated low density lipoprotein. AB - The formation of cholesterol-loaded macrophage foam cells in arterial tissue may occur by the uptake of modified lipoproteins via the scavenger receptor pathway. The macrophage scavenger receptor, also called the acetylated low density lipoprotein (Ac-LDL) receptor, has been reported to recognize Ac-LDL as well as oxidized LDL species such as endothelial cell-modified LDL (EC-LDL). We now report that there is another class of macrophage receptors that recognizes EC-LDL but not Ac-LDL. We performed assays of 0 degrees C binding and 37 degrees C degradation of 125I-Ac-LDL and 125I-EC-LDL by mouse peritoneal macrophages. Competition studies showed that unlabeled Ac-LDL could compete for only 25% of the binding and only 50% of the degradation of 125I-EC-LDL. Unlabeled EC-LDL, however, competed for greater than 90% of 125I-EC-LDL binding and degradation. Unlabeled Ac-LDL was greater than 90% effective against 125I-Ac-LDL; EC-LDL competed for about 80% of 125I-Ac-LDL binding and degradation. Copper-oxidized LDL behaved the same as EC-LDL in all the competition studies. Copper-mediated oxidation of Ac-LDL produced a superior competitor which could now displace 90% of 125I-EC-LDL binding. After 5 h at 37 degrees C in the presence of ligand, macrophages accumulated six times more cell-associated radioactivity from 125I-EC LDL than from 125I-Ac-LDL, despite approximately equal amounts of degradation to trichloroacetic acid-soluble products, which may imply different intracellular processing of the two lipoproteins. Our results suggest that 1) there is more than one macrophage "scavenger receptor" for modified lipoproteins; and 2) oxidized LDL and Ac-LDL are not identical ligands with respect to macrophage recognition and uptake. PMID- 2914925 TI - Affinity of single- or double-stranded oligodeoxyribonucleotides containing a thymine photodimer for T4 endonuclease V. AB - A gene for T4 endonuclease V was constructed by joining chemically synthesized oligodeoxyribonucleotides and expressed efficiently in Escherichia coli under the control of the E. coli tryptophan promoter. Overproduced T4 endonuclease V, which can cleave thymine photodimers as well as the corresponding phosphodiester linkage of DNA, was used to investigate the precise mode of the reaction with single- or double-stranded synthetic DNA fragments containing a thymine photodimer. The substrates, three oligodeoxyribonucleotides, d(GCGGTTGGCG) (10 mer), d(CGAAGGTTGGAAGC) (14-mer), and d(CACGAAGGTTGGAAGCAC) (18-mer), were prepared by UV irradiation of the nascent oligonucleotides. These single-stranded oligonucleotides were cleaved by the enzyme with a concentration 100 times higher than that required for the corresponding duplexes. The Km values for the TT duplex (14- and 18-mer) were found to be on the order of 10(-8) M. Dissociation constants for the 14- and 18-mer duplexes were measured by a binding assay on a nitrocellulose filter and found to be 10(-9). PMID- 2914926 TI - 19F nuclear magnetic resonance as a probe of the spatial relationship between the heme iron of cytochrome P-450 and its substrate. AB - The distance between the heme iron of ferrous cytochrome P-450-CAM and a fluorine label attached to the 9-methyl carbon of its substrate, (1R)-(+)-camphor, has been determined using 19F NMR. This investigation uses the Solomon-Bloembergen equation to measure the distance from a paramagnetic heme iron to a fluorine probe incorporated into a substrate that is not in fast exchange. The structural identity of the substrate analogue, 9-fluorocamphor, has been established using one- and two-dimensional NMR methods and mass spectrometry. The relaxation rate of 9-fluorocamphor bound to high-spin paramagnetic ferrous P-450-CAM has been studied at 188, 282, and 376 MHz, and the correlation time has been directly determined from the frequency dependence of the relaxation rate. When the substrate analogue was bound to the low-spin diamagnetic ferrous-CO derivative of the enzyme, the relaxation rate was found to be 100 times slower and was therefore neglected in the distance calculation. The relaxation data for the paramagnetic system and the correlation time have been used to calculate a distance of 3.8 A between the heme iron and the C-9 fluoride. A fit of the distance and the chemical shift data to the pseudocontact shift equation predicts an angle of approximately 52 degrees between the heme normal and the Fe-F vector. The solution state Fe-F distance is somewhat shorter and the angle between the heme normal and the Fe-F vector slightly larger for the substrate-bound ferrous enzyme reported herein than the analogous values for the substrate-bound ferric enzyme determined in the solid state by x-ray crystallography. These differences may reflect a structural change at the substrate-binding site upon reduction of the iron. PMID- 2914927 TI - Amino-terminal propeptide of human pro-alpha 2(V) collagen conforms to the structural criteria of a fibrillar procollagen molecule. AB - We have determined the nucleotide sequence of a cDNA clone encoding the amino terminal portion of human alpha 2(V) procollagen and found that the structure of the 186-residue amino-terminal propeptide closely resembles those of the fibril forming procollagens. Juxtaposed to a 26-residue leader peptide, pro-alpha 2(V) exhibits a characteristic cysteine-rich globular region followed by 24 Gly-X-Y repeats which are interrupted by two short non-collagenous sequences. Upon closer examination, each of these two sequences was noted to display structural motifs characteristic of either pro-alpha 1(I) and pro-alpha 1(III) collagens or pro alpha 1(II) collagen, respectively. Finally, within the amino-terminal telopeptide, a putative amino-terminal proteinase cleavage site, Ala-Gln, was identified. This latter finding strongly suggests that the alpha 2(V) amino terminal propeptide can be potentially processed and thus leaves unresolved the issue pertaining to the nature of the collagenase-resistant sequence that is retained by mature type V collagen molecules. PMID- 2914928 TI - Alterations of phospholipid metabolism by phorbol esters and fatty acids occur by different intracellular mechanisms in cultured glioma, neuroblastoma, and hybrid cells. AB - Differences between the influences of phorbol esters (such as 4 beta-12-O tetradecanoylphorbol 13-acetate) and of fatty acids (such as oleic acid) on the synthesis and turnover of phosphatidylcholine (PtdCho) and other phospholipids have been studied in glioma (C6), neuroblastoma (N1E-115), and hybrid (NG108-15) cells in culture using [methyl-3H]choline, [32P]Pi, [1,2-14C]ethanolamine, or 1 14C-labeled fatty acids as lipid precursors. 100-500 microM oleic acid stimulated PtdCho synthesis 3- to 5-fold in all three cell lines, but had little influence on chase of choline label following a 24-h pulse. Phorbol ester (50-200 nM) stimulated PtdCho synthesis 1.5- to 3-fold in C6 cells, was without effect in N1E 115 cells, and had intermediate effects on NG108-15 cells. Phorbol ester stimulated both uptake of extracellular choline and synthesis of PtdCho, whereas fatty acid stimulated only synthesis. Release of radioactivity from 24-h pulse labeled PtdCho to the medium was enhanced by phorbol ester in C6 cells. Incorporation of [32P]Pi, primarily into PtdCho, was stimulated, whereas utilization of [1,2-14C]ethanolamine or 1-14C-fatty acid was little altered by phorbol ester. C6 cells "down-regulated" with phorbol ester lost the stimulatory response of subsequent treatment with phorbol esters on PtdCho synthesis, but the response to fatty acid was enhanced. Fatty acid had little influence on the relative binding of phorbol ester or "translocation" of phorbol ester binding sites. Accordingly, metabolism of phospholipids in these cultured cells of neural origin is markedly influenced by cell type, phospholipid class, condition of incubation medium, and nature of stimulator. Phorbol esters and fatty acids appear to enhance phospholipid synthesis and turnover by distinct intracellular mechanisms. PMID- 2914929 TI - Comparative analysis of phosphorylation of translational initiation and elongation factors by seven protein kinases. AB - Four initiation factors (eIF-2, -3, -4B, and -4F), previously shown to be phosphorylated in vivo, are each phosphorylated to a significant extent in vitro (greater than 0.3 mol of phosphate/mol of factor) by at least three different protein kinases. An S6 kinase from liver, an active form of protease-activated kinase II which modifies the same sites on S6 as those phosphorylated in vivo in response to mitogens, phosphorylates the beta subunit of eIF-2, eIF-3 (p120 p130), eIF-4B, and eIF-4F (p220). The Ca2+, phospholipid-dependent protein kinase phosphorylates eIF-2 beta, eIF-3 (p170, p120-p130), eIF-4B, and eIF-4F (p220, p25). The cAMP-dependent protein kinase significantly modifies eIF-4B and, to a lesser extent, eIF-3 (p130). Casein kinase I incorporates phosphate only into eIF 4B, but to a limited extent. Casein kinase II phosphorylates eIF-2 beta, eIF-3 (p170, p120), and eIF-4B, while protease-activated kinase I modifies eIF-3 (p170, p120-p130), eIF-4B, and eIF-4F (p220). The mitogen-stimulated S6 kinase from 3T3 L1 cells, activated in response to insulin, does not phosphorylate any of the initiation factors. There is no significant incorporation of phosphate into eIF-2 alpha or -gamma, eIF-4A, eIF-4C, eIF-4D, EF-1, or EF-2 by any of the protein kinases examined. Phosphopeptide mapping of tryptic digests of the phosphorylated subunits shows that the individual protein kinases modify different sites. The sites phosphorylated in vitro reflect those modified in vivo as shown with eIF-4F in concomitant studies with reticulocytes treated with tumor-promoting phorbol ester (Morley, S.J., and Traugh, J. A. J. Biol. Chem., in press). Thus, we have identified multipotential protein kinases which modify four initiation factors phosphorylated in vivo and have shown that phosphorylation of these translational components can be coordinately regulated. PMID- 2914930 TI - Deduced sequence of a malate synthase polypeptide encoded by a subclass of the gene family. AB - We analyzed five malate synthase cDNA clones from the higher plant Brassica napus L. We determined the complete mRNA sequence and showed that the longest cDNA clone, pMS1, contains the entire protein coding region. The deduced polypeptide consists of 561 amino acids with a molecular mass of 63,700 daltons. To discern whether the cloned mRNAs represent distinct malate synthase polypeptides, we compared restriction maps and partial nucleotide sequence of the cDNA clones as well as their pattern of hybridization with restriction fragments in nuclear DNA. The results suggest that the five cloned mRNAs are encoded by either a single gene or by highly conserved members of the gene family. PMID- 2914931 TI - Calcium-binding proteins in the parathyroid gland. Detailed studies of parathyroid secretory protein. AB - In order to identify calcium (Ca2+)-binding proteins in the parathyroid gland, we used electrophoretic blots of proteins separated by a two-dimensional nondenaturing/denaturing gel system and incubated them with 45Ca2+. Parathyroid secretory protein (PSP) and proteins with approximate molecular weights of 98,000, 88,000, 58,000, and 30,000 were noted to bind Ca2+ in cytosolic fractions from bovine parathyroid, adrenal, and pituitary glands. However, differences in the binding affinity and capacity of the various proteins were observed. PSP displayed a low affinity and high binding capacity for Ca2+. In the presence of 5 mM MgCl2 and 60 mM KCl, native PSP (immobilized on nitrocellulose filters) bound 7.5 mol of Ca2+/mol of protein monomer with an apparent Kd of 1.1 mM. Immunoblotting identified the association of PSP with parathyroid cell membranes in a Ca2+-dependent manner. This property, together with its heat stability, distinguished PSP from other cytosolic Ca2+-binding proteins which were identified. There was also evidence for a Ca2+-dependent protein-protein interaction (aggregation) of PSP present in a Nonidet P-40 extract of cell membranes. The high Ca2+ binding capacity of PSP and its Ca2+-dependent membrane association may be features that make PSP a potentially important protein in secretory cells. PMID- 2914932 TI - Hisactophilin, a histidine-rich actin-binding protein from Dictyostelium discoideum. AB - The purification, cloning, and complete cDNA-derived sequence of a 17-kDa protein of Dictyostelium discoideum are described. This protein binds to F-actin in a pH dependent and saturable manner. It induces actin polymerization in the absence of Mg2+ or K+, and is enriched in the submembranous region of the amoeboid cells as indicated by immunofluorescence labeling of cryosections. The mRNA as well as the protein are present throughout growth and all stages of development. The protein is detected in both soluble and particulate fractions of the cells. From a plasma membrane-enriched fraction, minor amounts of the protein are stepwise solubilized with 1.5 M KCl, 0.1 M NaOH, and Triton X-100, but most of the protein is only solubilized with 1% sodium dodecyl sulfate. As judged by the apparent molecular mass in sodium dodecyl sulfate-polyacrylamide gels, immunological cross reactivity, and two-dimensional electrophoresis, the 17-kDa proteins from the soluble and particulate fraction resemble each other. The cDNA sequence does not reveal any signal peptide, trans-membrane region, or N-glycosylation site. Southern blots hybridized with a cDNA probe that spans the entire coding region show that the 17-kDa protein is encoded by a single gene. The most characteristic feature of the protein is its high content of 31 histidine residues out of 118 amino acids. We designate this protein as hisactophilin and suggest that this histidine-rich protein responds in its actin-binding activity to changes in cellular pH upon chemotactic signal reception. PMID- 2914933 TI - Differences between enamel-related and cementum-related dentin in the rat incisor with special emphasis on the phosphoproteins. AB - In order to determine whether qualitative and quantitative differences exist between the non-collagenous proteins of crown and root dentin, rat incisors were separated into their enamel- and cementum-related dentin portions (ERD and CRD, respectively). Isolation of the mineral-bound proteins was performed under nondegradative conditions. Analytical procedures included DEAE-chromatography on high pressure liquid chromatography, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and determination of phosphate, protein, and hydroxyproline. The results have shown that considerable differences exist among the two dentins with respect to the quantity of the various phosphoproteins. For this group of proteins as a whole, the ERD contains about 2 times the amount of organic phosphate found in the CRD and about 1.4 times the amount of protein. The content of higher phosphorylated phosphoproteins was about 4 times higher in the ERD than in the CRD, whereas the reverse was shown for the lower phosphorylated phosphoproteins. All differences were found to be statistically significant. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that while the ERD contains phosphoproteins with an apparent molecular mass of 98 kDa, the CRD contains two classes of phosphoproteins one of 98 and one of 88 kDa. The relevance of the observed differences in phosphoprotein distribution is discussed in relation to their possible role in mineralization. PMID- 2914934 TI - Phospholipid storage in the secretory granule of the mast cell. AB - A spontaneous membrane assembly process has been postulated to account for the rapid perigranular membrane enlargement which occurs during mast cell secretory granule activation. This process requires the presence of a phospholipid store in the quiescent granule. By using purified granules with intact membranes we have determined the total phospholipid content of the average quiescent granule. The results suggest that the average quiescent granule contains sufficient phospholipid to sustain at least a trebling of its perigranular membrane surface area during activation. As much as two-thirds of the total cellular phospholipid is found in the granules, and since a large portion of this phospholipid is extruded into the extracellular space along with the granule matrix during exocytosis, it is implied that this phospholipid can serve as the substrate for the formation of the lipid-derived mediators of inflammation. PMID- 2914935 TI - The calmodulin and F-actin binding sites of smooth muscle caldesmon lie in the carboxyl-terminal domain whereas the molecular weight heterogeneity lies in the middle of the molecule. AB - Caldesmons are major Ca2+-calmodulin regulated F-actin binding proteins of smooth and non-muscle cells that have been implicated as components of a thin filament regulatory system. Chicken gizzard caldesmons are monomeric proteins of Mr 140,000 and 135,000. We have employed enzymatic and chemical cleavage methods in order to dissect the protein to locate the Ca2+-calmodulin and F-actin binding domain and the site of molecular weight heterogeneity. Using a novel mapping procedure that employs partial chemical cleavage at cysteine residues, we show that both caldesmon polypeptides contain 2 cysteine residues located approximately 28,000 from the protein's amino terminus and the second approximately 25,000 from the carboxyl terminus. Identification of the composition of partial cleavage products with region-specific antibodies is consistent with this derived map. The apparent molecular weight heterogeneity was found to lie in the approximately 80,000 region between the 2 cysteine residues and therefore is not due to proteolytic processing. Digestion with alpha chymotrypsin yields a relatively stable basic Mr 40,000 Ca2+-calmodulin and F actin binding fragment that we have purified and characterized. The chymotryptic 40,000 fragment contains the 25,000 carboxyl-terminal fragment and therefore is derived from the carboxyl-terminal region of caldesmon. The 25,000 fragment obtained after chemical cleavage at cysteine under native conditions has also been purified and shown to bind F-actin and Ca2+-calmodulin. Surprisingly, the purified carboxyl 25,000 fragment, unlike the reduced intact monomer, cross-links F-actin into tightly ordered bundles in which the filaments are in register. PMID- 2914936 TI - Characterization of the dermatan sulfate proteoglycans, DS-PGI and DS-PGII, from bovine articular cartilage and skin isolated by octyl-sepharose chromatography. AB - Two forms of dermatan sulfate proteoglycans, called DS-PGI and DS-PGII, have been isolated from both bovine fetal skin and calf articular cartilage and characterized. The proteoglycans were isolated using either (a) molecular sieve chromatography under conditions where DS-PGI selectively self-associates or (b) chromatography on octyl-Sepharose, which separates DS-PGI from DS-PGII based on differences in the hydrophobic properties of their core proteins. The NH2 terminal amino acid sequence of DS-PGI from skin and cartilage is identical. The NH2-terminal amino acid sequence of DS-PGII from skin and cartilage is identical. However, the amino acid sequence data and tryptic peptide maps demonstrate that the core proteins of DS-PGI and DS-PGII differ in primary structure. In DS-PGI from bovine fetal skin, 81-84% of the glycosaminoglycan was composed of IdoA GalNAc(SO4) disaccharide repeating units. In DS-PGI from calf articular cartilage, only 25-29% of the glycosaminoglycan was composed of IdoA-GalNAc(SO4). In DS-PGII from bovine fetal skin, 85-93% of the glycosaminoglycan was IdoA GalNAc(SO4), whereas in DS-PGII from calf articular cartilage, only 40-44% of the glycosaminoglycan was IdoA-GalNAc(SO4). Thus, analogous proteoglycans from two different tissues, such as DS-PGI from skin and cartilage, possess a core protein with the same primary structure, yet contain glycosaminoglycan chains which differ greatly in iduronic acid content. These differences in the composition of the glycosaminoglycan chains must be determined by tissue-specific mechanisms which regulate the degree of epimerization of GlcA-GalNAc(SO4) into IdoA GalNAc(SO4) and not by the primary structure of the core protein. PMID- 2914937 TI - Isolation and characterization of the gene and cDNA encoding human mitochondrial creatine kinase. AB - Creatine kinase (CK; EC 2.7.3.2) isoenzymes play prominent roles in energy metabolism. Nuclear genes encode three known CK subunits: cytoplasmic muscle (MCK), cytoplasmic brain (BCK), and mitochondrial (MtCK). We have isolated the gene and cDNA encoding human placental MtCK. By using a dog heart MCK cDNA derived probe, the 7.0-kb EcoRI fragment from one cross-hybridizing genomic clone was isolated and its complete nucleotide sequence determined. A region of this clone encoded predicted amino acid sequence identical to residues 15-26 of the human heart MtCK NH2-terminal protein sequence. The human placental MtCK cDNA was isolated by hybridization to a genomic fragment encoding this region. The human placental MtCK gene contains 9 exons encoding 416 amino acids, including a 38 amino acid transit peptide, presumably essential for mitochondrial import. Residues 1-14 of human placental MtCK cDNA-derived NH2-terminal sequence differ from the human heart MtCK protein sequence, suggesting that tissue-specific MtCK mRNAs are derived from multiple MtCK genes. RNA blot analysis demonstrated abundant MtCK mRNA in adult human ventricle and skeletal muscle, low amounts in placenta and small intestine, and a dramatic increase during in vitro differentiation induced by serum-deprivation in the non-fusing mouse smooth muscle cell line, BC3H1. These findings demonstrate coordinate regulation of MtCK and cytosolic CK gene expression and support the phosphocreatine shuttle hypothesis. PMID- 2914938 TI - Gene family of male-specific testosterone 16 alpha-hydroxylase (C-P-450(16 alpha)) in mice. Organization, differential regulation, and chromosome localization. AB - Three genes in the testosterone 16 alpha-hydroxylase (C-P-450(16 alpha)) family, ca, cb, and cc, are characterized. The sizes of the genes are approximately 4.5 to 5.2 kilobase pairs, and all three consist of nine exons with junctions at identical sites. Gene ca is identified as the male-specific, androgen-dependent C P-450(16 alpha) gene in adult mice, since the exonic sequence matched 100% to the cDNA, pc16 alpha-2 (Wong, G., Kawajiri, K., and Negishi, M. (1987) Biochemistry 26, 8683-8690). Gene cb and cc are organized in tandem within 18-kilobase pair DNA. Their encoded P-450s contain an approximate 94% nucleotide sequence similarity to the C-P-450(16 alpha). The high similarity in gene nucleotide sequences, including the introns and flanking regions, suggests a combination of an ancestral gene duplication and gene conversion as a mechanism for evolution of the C-P-450(16 alpha) family. Gene ca shows male-specific expression in mouse kidney as well as in liver; gene cb, neither sex-specific nor androgen-dependent, is seen only in liver; gene cc is not expressed in either adult mouse liver or kidney. Expression of these three genes is not detected in adult mouse lung. It appears, therefore, that the C-P-450(16 alpha) gene family includes a large number of genes whose expressions are differentially regulated. Southern hybridization of C-P-450(16 alpha) cDNA to genomic DNAs from mouse-hamster somatic hybrid cells localizes tentatively this gene family on mouse chromosome 15. The recombination frequency in BXD recombinant inbred mice suggests that the C-P-450(16 alpha) gene family is approximately 16M from the 55-kDa locus. PMID- 2914940 TI - Purification and characterization of protein phosphatase 1I activating kinase from bovine brain cytosolic and particulate fractions. AB - The activating kinase of protein phosphatase 1I is distributed in approximately equal amounts between the cytosolic and particulate fractions of bovine brain homogenates. Both species of this protein kinase have been purified to near homogeneity. The cytosolic form, purified about 7,000-fold, has an apparent Mr = approximately 75,000, as estimated by gel filtration chromatography on Sephacryl S-300. The enzyme contains two subunits, with apparent Mr = 52,000 and 46,000, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Both subunits undergo phosphorylation when the enzyme is incubated with Mg2+ and [gamma-32P]ATP. Peptide maps of the two subunits are different, and rabbit antibodies to the 52-kDa subunit show only very minor cross-reactivity to the 46 kDa subunit. These observations indicate that the two subunits are different. The species of protein phosphatase 1I activating kinase that is associated with the membrane fraction has an apparent Mr = approximately 105,000 as estimated by gel filtration. This species also contains two subunits, with apparent Mr = 52,000 and 46,000, the properties of which are very similar, if not identical, to those of the two subunits comprising the cytosolic form of the protein kinase. PMID- 2914939 TI - A single gene codes for the beta subunits of smooth and skeletal muscle tropomyosin in the chicken. AB - A chicken genomic DNA library was screened with a full length cDNA corresponding to the beta subunit of smooth muscle tropomyosin. When hybridized with RNAs isolated from various tissues, this cDNA recognizes two mRNA species: one of 1.3 kilobase pairs present only in smooth muscle and one of 1.6 kilobase pairs present only in skeletal muscle. Two overlapping recombinant phages were shown to contain the entire locus and were further characterized. This locus contains 11 exons and spans approximately 13 kilobase pairs. Exon 1 (amino acids 1-38) contains the 5'-untranslated region which is common to the two mRNAs. Exons 6 (amino acids 189-213) and 11 (amino acids 258-284) contain sequences which are present exclusively in the 1.3-kilobase pair smooth muscle mRNA while exons 7 and 10, which code for an analogous region, contain sequences which are present exclusively in the 1.6-kilobase pair skeletal muscle mRNA (exons 10 and 11 also contain the entire 3'-untranslated regions of the corresponding mRNAs). Other exons, 2 to 5 (amino acids 39-188) and 8 and 9 (amino acids 214-257), contain sequences which are present in both mRNAs. Our results indicate that both the smooth and skeletal beta-tropomyosin mRNAs are derived from transcripts of a single gene with a unique promoter by a differential splicing mechanism. PMID- 2914941 TI - Transduction of cytochrome P3-450 by retroviruses: constitutive expression of enzymatically active microsomal hemoprotein in animal cells. AB - Cell lines were established which produce replication-defective ecotropic and amphotropic host range recombinant retroviruses containing the cDNA for mouse cytochrome P3-450 as well as the bacterial Neo gene for G418 resistance. The G418 resistant clones derived from virus-infected cultures were analyzed for the expression, subcellular localization, and catalytic activities of the cytochrome P3-450. Southern blot analysis of the genomic DNAs indicates that the viral DNA was stably integrated into the cellular DNA. Western blot analysis of the proteins showed that the size of the constitutively expressed product was Mr 54,000, indistinguishable from the cytochrome P3-450 found in mouse liver microsomes. Spectral characterization of the P3-450 proteins indicates that the newly synthesized apoprotein incorporated heme and integrated into the microsomes. Enzymatic analysis of the cell homogenates in vitro and of the dividing cells in situ showed very high acetanilide hydroxylase activity and very low aryl hydrocarbon hydroxylase activity, a diagnostic feature of the cytochrome P3-450. The precise transmission of the recombinant retroviral sequences into the target cells and the exceptional fidelity of expression of the enzyme in cells will allow the analysis of an increasing number of cloned genes of cytochrome P 450s by defining the individual enzyme specificities, their physiological role in cells, and consequences of their functional expression, such as in toxicity, mutagenesis, and carcinogenesis. PMID- 2914942 TI - A single base mutation that converts glycine 907 of the alpha 2(I) chain of type I procollagen to aspartate in a lethal variant of osteogenesis imperfecta. The single amino acid substitution near the carboxyl terminus destabilizes the whole triple helix. AB - Type I procollagen was examined in cultured skin fibroblasts from a patient with a lethal variant of osteogenesis imperfecta. About half of the pro-alpha chains were post-translationally overmodified and had a decreased thermal stability. The vertebrate collagenase A fragment had a normal thermal stability, but the B fragment had a decreased thermal stability. Therefore, there was a change in primary structure in amino acids 776-1014 of either the alpha 1(I) or alpha 2(I) chain. Three of five cDNA clones for the alpha 2(I) chain contained a single-base substitution of an A for a G that converted the codon for glycine at amino acid position 907 to aspartate. Complete nucleotide sequencing of bases coding for amino acids 776 to 1014 of the alpha 2(I) chain was carried out in one cDNA clone that contained the mutation in the glycine codon and in one that did not. Also, nucleotide sequencing was performed of bases coding for amino acids 776-1014 of the alpha 1(I) chain in seven independent cDNA clones. No other mutations were found. Therefore, the single base substitution that converts glycine 907 in the alpha 2(I) chain to aspartate is solely responsible for the decreased thermal stability of the type I procollagen synthesized by the proband's fibroblasts. Also, glycine 907 of the alpha 2(I) chain is an important component of a cooperative block that determines the melting temperature of the whole molecule. PMID- 2914943 TI - The isolation and chemical characterization of phosphorylated enkephalin containing peptides from bovine adrenal medulla. AB - There is increasing evidence that the opioid peptide precursor, proenkephalin A, and its products undergo extensive post-translational modification, in addition to the cleavage at dibasic amino acid sites. We have used an antiserum directed toward the C terminus of Met-enkephalin Arg6-Phe7 in a radioimmunoassay to monitor the purification to homogeneity of four peptide B variants from bovine adrenal medulla, using gel filtration, anion exchange chromatography, and reverse phase high performance liquid chromatography. Amino acid sequence analysis, together with immunochemical data, confirmed that each comprised the primary sequence, proenkephalin A-(209-239). In addition, three of the four variants were shown to be phosphorylated by alkaline phosphatase digestion, microphosphate analysis, and ethanethiol derivatization coupled with amino acid sequence analysis; these variants were shown to have 1, 2, or 3 phosphate groups per peptide chain, which corresponded to their increasing acidic nature. The phosphorylation sites were clustered together at positions Ser7, Ser13, and Ser15 and were in close association with acidic residues. The clustering of phosphorylated residues is unique among regulatory peptide precursors. This region of proenkephalin A is well conserved, which suggests that it constitutes an important novel functional domain. PMID- 2914944 TI - Hormonotoxins. Preparation and characterization of ovine luteinizing hormone gelonin conjugate. AB - With the aim of targeting toxins to selected cells in the gonad, we have prepared conjugates of ovine luteinizing hormone (oLH) with a single chain ribosome inactivating protein called gelonin. The two proteins were thiolated by using N succinimidyl-3-(2-pyridyldithio)propionate and subsequently reacted under appropriate conditions to form oLH-S-S-gelonin complex. A complete biochemical analysis of thiolated oLH and oLH-gelonin conjugates has been performed. The linkage of the hormone to the toxin probably occurred through a single amino group in the alpha-subunit, with the beta-subunit remaining free. Modification of a single amino group on the alpha-subunit reduced receptor binding and immunological reactivity of the thiolated oLH, but subsequent complexing with the toxin-gelonin did not seriously compromise these activities. oLH and gelonin were calculated to be present in a 1:1 ratio in the hormonotoxin preparation. The conjugate retained significant steroidogenic activity in rat granulosa cells. Upon reaction with mouse tumor Leydig cells (MA-10 cells), the toxin component of the complex became internalized to a sufficient degree to effectively inhibit protein synthesis. The studies provide a rational basis for the design and study of large hormonotoxins. PMID- 2914945 TI - 113Cd NMR of Cd2+-substituted carboxypeptidase. Support for a hexa-coordinate metal ion in the presence of inhibitors. AB - The liquid-state 113Cd NMR data of carboxypeptidase A in the presence and absence of inhibitors obtained by Gettins (Gettins, P. (1986) J. Biol. Chem. 261, 15513 15518) are analyzed in terms of whether the inhibitors displace water from Cd2+ upon binding to the protein. This question is addressed by applying the single crystal data and the methods introduced by Honkonen and Ellis (Honkonen, R. S., and Ellis, P. D. (1984) J. Am. Chem. Soc. 106, 5488-5497). Calculations based upon these data demonstrate that displacement of water by a carboxyl group should lead to significant shielding of a 113Cd resonance by approximately 100 ppm. Since the observed 113Cd chemical shifts for carboxypeptidase A are modest and deshielding (12-17 ppm), it is argued that the chemical shifts imply that water is not displaced from the Cd2+ center upon binding of inhibitors to carboxypeptidase A. Rather, the Cd2+ ion increases its coordination number from five to six upon binding of the inhibitor. PMID- 2914946 TI - Chicken oocytes and fibroblasts express different apolipoproteins-B-specific receptors. AB - We have previously characterized a 95-kDa plasma membrane receptor for low and very low density lipoproteins in chicken oocytes (George, R., Barber, D. L., and Schneider, W. J. (1987) J. Biol. Chem. 262, 16838-16847). We now report that somatic cells of chickens, such as fibroblasts, express a different receptor for these lipoproteins. This receptor has a Mr of 130,000 and is part of a regulatory system for cholesterol homeostasis analogous to the low density lipoprotein receptor pathway in mammalian cells. Oocytes produce only the 95-kDa receptor, while fibroblasts synthesize exclusively the 130-kDa receptor. In addition to their different Mr values, another distinctive feature of the two proteins was revealed by ligand blotting experiments: the oocyte receptor bound rabbit beta VLDL (a class of apolipoprotein-B and -E containing lipoprotein particles), whereas the fibroblast receptor did not. Furthermore, polyclonal rabbit antibodies that recognize the oocyte 95-kDa receptor failed to cross-react with the 130-kDa protein on fibroblasts [corrected]. We suggest that different receptors have evolved in the chicken in order to facilitate the deposition of lipids into oocytes (i.e. yolk formation) with concomitant maintenance of cholesterol homeostasis in extraoocytic tissues. PMID- 2914947 TI - The reassociation of factor Va from its isolated subunits. AB - Factor Va is an essential cofactor for the activation of prothrombin catalyzed by factor Xa. The cofactor is a heterodimer composed of a light chain and a heavy chain that are associated noncovalently in the presence of divalent metal ions. The kinetics of the formation of factor Va from the isolated and separated subunits was examined by the time-dependent regain in cofactor activity using direct assays of prothrombin activation catalyzed by prothrombinase. The rate of reassociation at saturating concentrations of calcium ions was slow with a strong temperature dependence. The product of the association reaction was indistinguishable from native factor Va on the basis of activity. The second order rate constant for the process at 37 degrees C in the presence of 2 mM CaCl2 was 1.58 X 10(5) M-1.min-1. Manganese ion increased the rate of regain of activity without influencing the extent of the reaction. The previous identification of a single reactive sulfhydryl in each subunit of factor Va permitted the modification of the separated subunits with sulfhydryl-directed fluorophores. Subunit reassociation was directly measured by fluorescence energy transfer using light chain modified with 6-acryloyl-2-dimethylaminonaphthalene (fluorescence donor) and heavy chain modified with fluorescein 5-maleimide (fluorescence acceptor). Fluorescence measurements indicate that the heavy and light chains associate tightly (Kd = 5.9 x 10(-9) M) and reversibly with a stoichiometry of 1:1. The dissociation of the subunits from the cofactor is first order with a rate constant of 1.03 X 10(-3) min-1. These interpretations were confirmed by physical measurements of subunit reassociation by sedimentation velocity studies. PMID- 2914948 TI - The major late promoter of adenovirus-2 is accurately transcribed by RNA polymerases IIO, IIA, and IIB. AB - Subunit IIa of mammalian RNA polymerase II contains at its C terminus 52 tandem repeats of the consensus sequence Tyr-Ser-Pro-Thr-Ser-Pro-Ser. This domain is unmodified in RNA polymerase IIA, extensively phosphorylated in RNA polymerase IIO, and absent from RNA polymerase IIB. In an effort to define the role of the C terminal domain, we have measured the transcriptional activity of purified RNA polymerases IIO, IIA, and IIB. The ability of each polymerase subspecies to transcribe the major late promoter of adenovirus-2 was examined in a polymerase dependent transcription system reconstituted from partially purified transcription factors. RNA polymerases IIO, IIA, and IIB are all capable of initiating specific transcripts from this promoter. The transcriptional activity was determined as a function of the concentration of RNA polymerase II, template DNA, and each of the essential general transcription factors. The transcriptional activities of RNA polymerases IIA and IIB were comparable and consistently greater than that of RNA polymerase IIO when assayed under the conditions described here. The kinetics of transcript formation is similar except that RNA polymerase IIO has a more pronounced lag. These results show that the C-terminal domain of subunit IIa is not essential for the accurate initiation of transcripts from the major late promoter of adenovirus-2 and that the effect of the C terminal domain is not likely mediated by the general transcription factors required for the expression of class II genes. PMID- 2914949 TI - Isolation, characterization, and synthesis of chrysobactin, a compound with siderophore activity from Erwinia chrysanthemi. AB - A catechcol-type siderophore, assigned the trivial name chrysobactin, was isolated from the phytopathogenic bacterium Erwinia chrysanthemi and characterized by degradation and spectroscopic techniques as N-[N2-(2,3 dihydroxybenzoyl)-D-lysyl]-L-serine. Chrysobactin, which was also obtained by chemical synthesis, was shown to be active in supplying iron to a group of mutants of E. chrysanthemi defective in biosynthesis of the siderophore. PMID- 2914950 TI - Complex-type asparagine-linked oligosaccharides in glycoproteins synthesized by Schistosoma mansoni adult males contain terminal beta-linked N acetylgalactosamine. AB - Many studies have shown that the human blood fluke Schistosoma mansoni contains glycoproteins whose oligosaccharide side chains are antigenic in infected hosts. We report here that adult male schistosomes synthesize glycoproteins containing complex-type N-linked chains that have structural features not commonly found in mammalian glycoproteins. Adult male worms were incubated in media containing either [3H]mannose, [3H]glucosamine, or [3H]galactose, and the metabolically radiolabeled oligosaccharides on newly synthesized glycoproteins were analyzed. Schistosomes synthesize triantennary- and biantennary-like complex-type asparagine-linked chains that contain mannose, fucose, N-acetylglucosamine, and N acetylgalactosamine. Interestingly, none of the complex-type chains contain sialic acid, and few of the chains contain galactose. Since N-acetylgalactosamine is not a common constituent of mammalian-derived N-linked chains, we investigated the position and linkage of this residue in the schistosome-derived glycopeptides. Virtually all of the N-acetylgalactosamine was beta-linked and in a terminal position. The unusual features of the S. mansoni glycoprotein oligosaccharides support the possibility that they may be involved in the host immune response to infection. PMID- 2914951 TI - Sequence-specific binding of arc repressor to DNA. Effects of operator mutations and modifications. AB - A set of arc operators with transition and/or transversion mutations at each operator base pair has been constructed. By determining the ability of Arc to bind these variant operators, the importance of each base pair for Arc recognition has been assessed. Methylation protection experiments have also been used to probe points of close contact between Arc and most of the mutant operators. These data, together with phosphate interference results obtained previously for the wild type operator, provide information about the operator surface that is contacted when Arc binds. PMID- 2914952 TI - Recognition of (dG)n.(dC)n sequences by endonuclease G. Characterization of the calf thymus nuclease. AB - We report the purification of endonuclease G (Ruiz-Carrillo, A., and Renaud, J. (1987) EMBO J. 6, 401-407) from calf thymus nuclei and whole tissue. The enzyme has been enriched 29,000-fold, and the activity was unambiguously identified with a 26-kDa protein after renaturation following sodium dodecyl sulfate polyacrylamide gel electrophoresis. The native nuclease behaves as a 50-kDa species by gel filtration, suggesting that it is composed of two subunits, presumably identical. In terms of absolute amounts, endonuclease G (endo G) is a nuclear enzyme although it was also detected in purified mitochondria. Endo G is highly specific for (dG)n.(dC)n tracts in DNA, nicking either strand of relaxed substrates with similar kinetics. The sensitivity of the homopolymer tracts is proportional to their length (from n = 8 to 29), insofar as the flanking sequences are constant. However, the overall rate of cleavage is influenced by the composition of the flanking DNA. Minor cleavage sites contain shorter (dG)n.(dC)n clusters (n = 3-7). Endo G efficiently cleaves (dC)n but not (dG)n runs in single-stranded DNA, suggesting that it may recognize an asymmetric strand conformation of the homopolymer tracts. Endo G does not recognize other homo(co)-polymer sequences or cruciform structures in DNA. PMID- 2914953 TI - Oxidative inactivation of rhodanese by hydrogen peroxide produces states that show differential reactivation. AB - Controlled conditions have been found that give complete reactivation and long term stabilization of rhodanese (EC 2.8.1.1) after oxidative inactivation by hydrogen peroxide. Inactivated rhodanese was completely reactivated by reductants such as thioglycolic acid (TGA) (100 mM) and dithiothreitol (DTT) (100 mM) or the substrate thiosulfate (100 mM) if these reagents were added soon after inactivation. Reactivability fell in a biphasic first order process. At pH 7.5, in the presence of DTT inactive rhodanese lost 40% of its reactivability in less than 5 min, and the remaining 60% was lost more gradually (t 1/2 = 3.5 h). TGA reactivated better than DTT, and the rapid phase was much less prominent. If excess reagents were removed by gel filtration immediately after inactivation, there was time-independent and complete reactivability with TGA for at least 24 h, and the resulting samples were stable. Reactivable enzyme was resistant to proteolysis and had a fluorescence maximum at 335 nm, just as the native protein. Oxidized rhodanese, Partially reactivated by DTT, was unstable and lost activity upon further incubation. This inactive enzyme was fully reactivated by 200 mM TGA. Also, the enzyme could be reactivated by arsenite and high concentrations of cyanide. Addition of hydrogen peroxide (40-fold molar excess) to inactive rhodanese after column chromatography initiated a time-dependent loss of reactivability. This inactivation was a single first order process (t 1/2 = 25 min). Sulfhydryl titers showed that enzyme could be fully reactivated after the loss of either one or two sulfhydryl groups. Irreversibly inactivated enzyme showed the loss of one sulfhydryl group even after extensive reduction with TGA. The results are consistent with a two-stage oxidation of rhodanese. In the first stage there can form sulfenyl and/or disulfide derivative(s) at the active site sulfhydryl that are reducible by thioglycolate. A second stage could give alternate or additional oxidation states that are not easily reducible by reagents tried to date. PMID- 2914954 TI - Manganese peroxidase from the lignin-degrading basidiomycete Phanerochaete chrysosporium. Transient state kinetics and reaction mechanism. AB - Stopped-flow techniques were used to investigate the kinetics of the formation of manganese peroxidase compound I (MnPI) and of the reactions of MnPI and manganese peroxidase compound II (MnPII) with p-cresol and MnII. All of the rate data were obtained from single turnover experiments under pseudo-first order conditions. In the presence of H2O2 the formation of MnPI is independent of pH over the range 3.12-8.29 with a second-order rate constant of (2.0 +/- 0.1) x 10(6) M-1 s-1. The activation energy for MnPI formation is 20 kJ mol-1. MnPI formation also occurs with organic peroxides such as peracetic acid, m-chloroperoxybenzoic acid, and p nitroperoxybenzoic acid with second-order rate constants of 9.7 x 10(5), 9.5 x 10(4), and 5.9 x 10(4) M-1 s-1, respectively. The reactions of MnPI and MnPII with p-cresol strictly obeyed second-order kinetics. The second-order rate constant for the reaction of MnPII with p-cresol is extremely low, (9.5 +/- 0.5) M-1 s-1. Kinetic analysis of the reaction of MnII with MnPI and MnPII showed a binding interaction with the oxidized enzymes which led to saturation kinetics. The first-order dissociation rate constants for the reaction of MnII with MnPI and MnPII are (0.7 +/- 0.1) and (0.14 +/- 0.01) s-1, respectively, when the reaction is conducted in lactate buffer. Rate constants are considerably lower when the reactions are conducted in succinate buffer. Single turnover experiments confirmed that MnII serves as an obligatory substrate for MnPII and that both oxidized forms of the enzyme form productive complexes with MnII. Finally, these results suggest the alpha-hydroxy acids such as lactate facilitate the dissociation of MnIII from the enzyme. PMID- 2914955 TI - Characterization of a thyroid sulfotransferase responsible for the 3-O-sulfation of terminal beta-D-galactosyl residues in N-linked carbohydrate units. AB - Calf thyroid microsomes were found to contain an enzyme which catalyzes the transfer of sulfate from 3'-phosphoadenosine 5'-phospho[35S]sulfate (PAPS) to C-3 of terminal galactose residues in beta 1----4 linkage to GlcNAc. This sulfotransferase is believed to be involved in the biosynthesis of the recently described Gal(3-SO4) capping groups present in the N-linked oligosaccharides of thyroglobulin (Spiro, R.G., and Bhoyroo, V. D. (1988) J. Biol. Chem. 263, 14351 14358). Assays with various native and modified glycopeptides indicated that the enzyme acted optimally on complex-type carbohydrate units in which beta-linked Gal has been uncovered by desulfation or brought into a terminal position by removal of sialyl and/or alpha-galactosyl residues. With fetuin asialoglycopeptides as acceptors (Km = 0.1 mM) the transfer of sulfate from PAPS (Km = 6.3 microM) had a pH optimum of approximately 7.0, required Mn2+ ions (10 50 mM) and was markedly stimulated by Triton X-100 (0.1%) and ATP (2 mM). The same enzyme apparently sulfated free N-acetyllactosamine (LacNAc; Km = 0.69 mM) and its ethyl glycoside, indicating that it had no absolute requirement for a peptide recognition site. Studies with a number of disaccharides related to LacNAc provided information relating to the specifying role of the beta 1----4 galactosyl linkage and the configuration at C-2 of the sugar to which it is attached. Hydrazine-nitrous acid-NaBH4 treatment of the 35S-labeled products from sulfotransferase action on asialoglycopeptides as well as on the ethyl glycoside of LacNAc yielded the same disaccharide, Gal(3-SO4) beta 1----4 anhydromannitol, as is obtained from a similar treatment of thyroglobulin. Subcellular distribution studies indicated that the PAPS:galactose 3-O-sulfotransferase is located in the Golgi compartment which is consistent with the late occurrence of the requisite beta-galactosylation step. It is proposed that in certain tissues the ultimate nature of the capping groups attached to glycoproteins containing terminal Gal beta 1----4GlcNAc sequences could be the result of a competition between this 3-O-sulfotransferase and sialyl- and/or alpha galactosyltransferases. PMID- 2914956 TI - The molecular defect in a COOH-terminal-modified and shortened mutant of human serum albumin. AB - Albumin Venezia is a fast migrating genetic variant of human serum albumin which, in heterozygous subjects, represents about 30% of the circulating protein. The molecular defect in this variant was studied in a subject possessing an atypical level of the mutant (80% of the total protein) and in other members of his family. Albumins, isolated from the sera of the propositus and his heterozygous relatives, were treated with CNBr and the resulting fragments analyzed by isoelectric focusing. The peptides were then isolated in a homogeneous form by reverse-phase high performance liquid chromatography and submitted to sequence analysis. The results show that albumin Venezia possesses a shortened polypeptide chain, 578 residues instead of 585, completely variant from residue 572 to the COOH-terminal end: sequence: (see text). This extensive modification may be accounted for by the deletion of exon 14 and translation to the first terminator codon of exon 15, which normally does not code for protein. The absence of a basic COOH-terminal dipeptide in the mature molecule can be explained by the probable action of serum carboxypeptidase N. Additional support for such action comes from examination of the remaining 20% of the total albumin of the propositus, which is found to contain an extra Arg at its COOH terminus, probably due to partial digestion by carboxypeptidase N. The low serum level of the variant in heterozygous subjects suggests that the COOH-terminal end of the molecule is critical for albumin stability. PMID- 2914957 TI - Increased incidence of CAD gene amplification in tumorigenic rat lines as an indicator of genomic instability of neoplastic cells. AB - It has been hypothesized that genomic instability is an important component of tumorigenesis. In an attempt to establish this relationship, we determined the frequencies with which two nontumorigenic and four tumorigenic rat liver epithelial cell lines underwent a particular type of genetic instability, gene amplification. By exposing cells to N-(phosphonoacetyl)-L-aspartate (PALA), a drug which specifically inhibits the aspartate transcarbamylase activity of the multifunctional CAD enzyme and selects for amplification of the CAD gene, we observed a striking parallel between the ability of these cell lines to become resistant to this drug and the ability of these same cells to form tumors after injection into day-old syngeneic rats. Cells of one highly tumorigenic line became resistant to PALA greater than 70 times more often than those of a non tumorigenic line. Molecular analyses of eight independent PALA-resistant subclones confirmed that, in each case, this resistance was due to amplification of the CAD gene. Thus, our results demonstrate the relationship between tumorigenicity and at least one measure of genomic instability, CAD gene amplification. The method developed in this study provides a quantitative, rapid indicator of tumorigenicity and should prove useful in trying to elucidate the underlying basis of genomic instability in neoplastic cells. PMID- 2914959 TI - High resolution proton NMR studies of gangliosides. Structure of two types of GD3 lactones and their reactivity with monoclonal antibody R24. AB - Ganglioside GD3 was converted at room temperature to two stable lactones, denoted as GD3 lactones I and II. The reaction sequence was presumed to be GD3----GD3 lactone I----GD3 lactone II based on the time course of their production. Lactone I behaved as a monosialoganglioside and lactone II as a neutral species. The two lactones were isolated by DEAE-Sephadex column chromatography. The positions of the inner ester linkages were investigated by two-dimensional J-correlated proton NMR spectroscopy. An ester linkage was most likely formed between the carboxyl group of the external sialic acid residue and C9-OH of the internal sialic acid residue in lactone I. In addition to this ester linkage, a second ester linkage between the carboxyl group of the internal sialic acid and C2-OH of the galactose residue was likely formed in lactone II. The structural changes induced by lactonization were further examined by their reactivity with the monoclonal antibody R24 (Puckel, C. S., Lloyd, K. O., Travassos, L. R., Dippold, W. G., Oettgen, H. F., and Old, L. J. (1982) J. Exp. Med. 155, 1133-1147), which reacted with GD3. R24 was found to bind weakly to GD3 lactone I, but not to GD3 lactone II. The results suggest that the monoclonal antibody requires both sialic acid residues for high affinity binding, and the complete lactonization results in a loss of negative charges and/or a change in the overall conformation of the oligosaccharide moiety which may account for the loss of binding. PMID- 2914958 TI - Molecular phenotypes in cultured maple syrup urine disease cells. Complete E1 alpha cDNA sequence and mRNA and subunit contents of the human branched chain alpha-keto acid dehydrogenase complex. AB - The activity of the branched-chain alpha-keto acid dehydrogenase complex is deficient in patients with the inherited maple syrup urine disease (MSUD). To elucidate the molecular basis of this metabolic disorder, we have isolated three overlapping cDNA clones encoding the E1 alpha subunit of the human enzyme complex. The composite human E1 alpha cDNA consists of 1783 base pairs encoding the entire human E1 alpha subunit of 400 amino acids with calculated Mr = 45,552. The human E1 alpha and the previously isolated human E2 cDNAs were used as probes in Northern blot analysis with cultured fibroblasts and lymphoblasts from seven unrelated MSUD patients. The results along with those of Western blotting have revealed five distinct molecular phenotypes according to mRNA and protein-subunit contents. These consist of type I, where the levels of E1 alpha mRNA and E1 alpha and E1 beta subunits are normal in cells, but E1 activity is deficient; Type II, where the E1 alpha mRNA is present in normal quantity, whereas the contents of E1 alpha and E1 beta subunits are reduced; Type III, where the level of E1 alpha mRNA is markedly reduced with a concomitant loss of E1 alpha and E1 beta subunits; Type IV, where the contents of both E2 mRNA and E2 subunits are markedly reduced; and Type V, where the E2 mRNA is normally expressed, but the E2 subunit is markedly reduced or completely absent. Type V includes thiamin responsive (WG-34) and certain classical MSUD cells. These molecular phenotypes have demonstrated the complexity of MSUD and identified the affected gene in different patients for further characterization. PMID- 2914960 TI - Regulation of collagen VI expression in fibroblasts. Effects of cell density, cell-matrix interactions, and chemical transformation. AB - Collagen VI expression was studied in cultured human skin fibroblasts and mouse 3T3 cells using cDNA probes specific for alpha 1(VI), alpha 2(VI), and alpha 3(VI) chains. A 2-3-fold increase of these mRNAs was observed when fibroblasts were grown at increasing densities while only minimal changes occurred for the mRNA levels of collagens I and III, fibronectin, and beta-actin. Changes in mRNA correlated well with an increased production of corresponding proteins as determined by immunological assays. A comparable increase of alpha 1(VI) and alpha 2(VI) but not of alpha 3(VI) chain mRNAs was found for fibroblasts grown in a three-dimensional collagen gel after gel contraction. These conditions resulted, however, in a decrease of steady-state levels of collagens I and III and actin mRNAs. Transformation of 3T3 cells by phorbol ester did not change collagen VI mRNAs but caused a 3-5-fold reduction in mRNA levels for the other extracellular matrix proteins. These data strongly imply different regulatory mechanisms for the expression of collagen VI compared with collagens I and III and fibronectin. The differences may be correlated to changes in cell shape and reflect the requirement for collagen VI as a cell-binding protein. PMID- 2914961 TI - Molecular cloning, nucleotide sequence, and tissue distribution of malonyl-CoA decarboxylase. AB - Malonyl-CoA decarboxylase was purified from goose uropygial gland, reduced, carboxymethylated, and digested with trypsin. Several peptides were purified by high performance liquid chromatography and their amino acid sequences determined. Oligonucleotide probes were prepared based on their amino acid sequences. Size selected RNA from the goose uropygial gland was used to construct cDNA libraries in lambda gt11 and pUC9 vectors. Immunological screening of the lambda gt11 cDNA library yielded one clone, lambda DC1, which contained a 2.2-kilobase pair insert; hybridization with the synthetic oligonucleotide probes confirmed its identity as malonyl decarboxylase. Screening of the pUC9 cDNA library with the insert of lambda DC1 as a probe detected one clone, pDC2, with an insert of 2.9 kilobase pairs. The nucleotide sequences of the two cDNAs revealed an open reading frame encoding a polypeptide of 462 amino acids. The deduced amino acid sequence was confirmed as malonyl-CoA decarboxylase by matching it to the amino acid sequences of three tryptic peptides derived from mature enzyme. Northern blot analysis of mRNA from goose brain, kidney, liver, lung, and gland revealed malonyl-decarboxylase mRNA of 3000 nucleotides. Since clone pDC2 contains a 2928 nucleotide insert, it represents nearly the full length of mRNA. Brain, kidney, lung, and liver contained less than 1% of the malonyl-CoA decarboxylase mRNA in the gland. Southern blot analysis of genomic DNA showed a single band in both liver and gland, suggesting that malonyl-CoA decarboxylase is a single copy gene. PMID- 2914962 TI - Amplification of a polymorphic dihydrofolate reductase gene expressing an enzyme with decreased binding to methotrexate in a human colon carcinoma cell line, HCT 8R4, resistant to this drug. AB - A methotrexate (MTX)-resistant human colon carcinoma cell line was obtained by growing HCT-8 cells in stepwise increasing concentrations of the drug. The resistant subline (HCT-8R4) was able to grow in the presence of 1 x 10(-4) M MTX and was found to have a 25-fold increase in the level of the target enzyme dihydrofolate reductase (DHFR), with a corresponding increase in DHFR gene copies as well as DHFR transcripts. Southern blot analysis of DNA from HCT-8R4 cells revealed the amplification of an altered gene. The amplified DHFR gene lacks an EcoRI restriction enzyme site in the coding region, normally present in other human cell lines. Sequence analysis of cDNA synthesized from transcripts in the MTX-resistant cell line revealed a base transition T----C at nucleotide position 91 resulting in a substitution of serine for phenylalanine. The dissociation constant for MTX binding to the HCT-8R4 enzyme was 1.25 nM, an 8-fold increase from the Kd 150 pM of purified wild type human DHFR. This decrease in binding of MTX to the HCT-8R4 DHFR is consistent with the predicted involvement of phenylalanine in the DHFR active site in hydrophobic interactions with MTX. This mutation plus the 25-fold increase in DHFR activity explains the high level of resistance of this subline to MTX. PMID- 2914963 TI - The lack of a role for protein kinase C in neurite extension and in the induction of ornithine decarboxylase by nerve growth factor in PC12 cells. AB - Nerve growth factor (NGF) causes pheochromocytoma cells (PC12) to undergo a number of physiological changes which mimic the differentiated neuronal cell, including neurite extension. We have examined protein kinase C (Ca2+/phospholipid dependent enzyme) as a potential signaling mechanism in NGF-stimulated neurite outgrowth and induction of the enzyme ornithine decarboxylase. Phorbol 12 myristate 13-acetate (PMA) can activate protein kinase C and induce ornithine decarboxylase in PC12 cells with kinetics which are similar to those of NGF induction, but only to levels about 10-fold lower. The induction of ornithine decarboxylase by both NGF and PMA is inhibited by cycloheximide and actinomycin D suggesting that both agents increase enzyme activity by increasing gene transcription. The evidence presented here, however, shows that the induction produced by the two agents is through two different pathways. First, maximal induction by NGF is increased when PMA is included in the media showing that the two effects are synergistic. Second, NGF does not cause induction of ornithine decarboxylase in the mutant PC12nnr5 cell line (Green, S.H., Rydel, R.E., Connolly, J.L., and Greene, L.A. (1986) J. Cell Biol. 103, 1967-1978) while added PMA does produce an induction of the enzyme. Finally, when protein kinase C is down-regulated by incubating PC12 cells with PMA in serum-containing or serum free medium for 24 h, the induction by PMA is completely inhibited, while the NGF induction is not affected. A recent study (Hall, F.L., Fernyhough, P., Ishii, D.N., and Vulliet, P.R. (1988) J. Biol. Chem. 263, 4460-4466) using sphingosine inhibition concluded that protein kinase C was required for NGF-stimulated neuritogenesis. In contrast, results presented here show that down-regulation of protein kinase C also has no effect on NGF-mediated neurite extension in PC12 cells grown in serum-free medium. Our data demonstrate that induction of ornithine decarboxylase and formation of neurites in PC12 cells by NGF does not require a protein kinase C-mediated pathway. PMID- 2914964 TI - Induction of rat hepatic N-nitrosodimethylamine demethylase by acetone is due to protein stabilization. AB - The N-nitrosodimethylamine demethylase (P450I-IE1) is induced severalfold in liver by giving rats ethanol, acetone, pyrazole, and other related small molecular weight compounds. This induction is not the result of an increase in IIE1 mRNA, but could be due to either an increase in translation rate or a decrease in protein degradation. To determine the mechanism of induction, we measured IIE1 synthesis and degradation rates in untreated and acetone-treated rats. This was accomplished by immunopurification of radiolabeled IIE1 protein using a specific monoclonal antibody subsequent to in vivo labeling of total cellular protein with either NaH14CO3 or [3H]leucine. We found that in rats fed acetone, the rate of IIE1 synthesis was not changed; however, IIE1 degradation was markedly altered. In untreated rats, IIE1 protein was degraded via a biphasic pathway consisting of both a rapid and slow component with approximate half-lives of 7 and 37 h, respectively. However, in acetone-treated rats, only a monophasic curve with a half-life of 37 h was observed. The abolition of the rapid degradation component of the IIE1 turnover cycle indicates that induction of IIE1 by acetone is primarily due to specific stabilization of IIE1 protein. Since acetone is also metabolized by IIE1, we believe that this may be a substrate induced enzyme stabilization. PMID- 2914965 TI - Antithrombin activity of fucoidan. The interaction of fucoidan with heparin cofactor II, antithrombin III, and thrombin. AB - Fucoidan, poly(L-fucopyranose) linked primarily alpha 1----2 with either a C3- or a C4-sulfate, is an effective anticoagulant in vitro and in vivo (Springer, G. F., Wurzel, H. A., McNeal, G. M., Jr., Ansell, N. J., and Doughty, M. F. (1957) Proc. Soc. Exp. Biol. Med. 94, 404-409). We have determined the antithrombin effects of fucoidan on the glycosaminoglycan-binding plasma proteinase inhibitors antithrombin III and heparin cofactor II. Fucoidan enhances the heparin cofactor II-thrombin reaction more than 3500-fold. The apparent second-order rate constant of thrombin inhibition by heparin cofactor II increases from 4 x 10(4) (in the absence of fucoidan) to 1.5 x 10(8) M-1 min-1 as the fucoidan concentration increases from 0.1 to 10 micrograms/ml and then decreases as fucoidan is increased above 10 micrograms/ml. The fucoidan reaction with heparin cofactor II thrombin is kinetically equivalent to a "template model." Apparent fucoidan heparin cofactor II and fucoidan-thrombin dissociation constants are 370 and 1 nM, respectively. The enhancement of thrombin inhibition by fucoidan, like heparin and dermatan sulfate, is eliminated by selective chemical modification of lysyl residues either of heparin cofactor II or of thrombin. The fucoidan antithrombin III reactions with thrombin and factor Xa are accelerated maximally 285- and 35-fold at fucoidan concentrations of 30 and 500 micrograms/ml, respectively. Using human plasma and 125I-labeled thrombin in an ex vivo system, the heparin cofactor II-thrombin complex is formed preferentially over the antithrombin III-thrombin complex in the presence of 10 micrograms/ml fucoidan. Our results indicate that heparin cofactor II is activated by fucoidan in vitro and in an ex vivo plasma system and suggest that the major antithrombin activity of fucoidan in vivo is mediated by heparin cofactor II and not by antithrombin III. PMID- 2914966 TI - Revised amino acid sequence, crystallization, and preliminary x-ray diffraction analysis of acidic phospholipase A2 from the venom of Agkistrodon halys blomhoffii. AB - The complete amino acid sequence of acidic Agkistrodon halys blomhoffii phospholipase A2 has been redetermined by a combination of manual and automatic Edman degradations. Acidic A. halys blomhoffi phospholipase is a single polypeptide chain consisting of 122 amino acids and is highly homologous in sequence with corresponding regions of phospholipase A2 from a variety of sources. Prism crystals of acidic A. halys blomhoffii phospholipase have been reproducibly grown from 2-methyl-2,4-pentanediol solution adjusted to pH 8.0 with 50 mM Tris-HCl buffer in the presence of 10 mM CaCl2. The crystals belong to space group P6(1)22 or P6(5)22 with hexagonal unit cell dimensions of a = b = 76.22 A and C = 76.56 A. One molecule occupies the asymmetric unit of the crystal. The diffraction extends to at least 2.5 A. PMID- 2914967 TI - A planar model of the knee joint to characterize the knee extensor mechanism. AB - A simple planar static model of the knee joint was developed to calculate effective moment arms for the quadriceps muscle. A pathway for the instantaneous center of rotation was chosen that gives realistic orientations of the femur relative to the tibia. Using the model, nonlinear force and moment equilibrium equations were solved at one degree increments for knee flexion angles from 0 (full extension) to 90 degrees, yielding patellar orientation, patellofemoral contact force and patellar ligament force and direction with respect to both the tibial insertion point and the tibiofemoral contact point. The computer-derived results from this two-dimensional model agree with results from more complex models developed previously from experimentally obtained data. Due to our model's simplicity, however, the operation of the patellar mechanism as a lever as well as a spacer is clearly illustrated. Specifically, the thickness of the patella was found to increase the effective moment arm significantly only at flexions below 35 degrees even though the actual moment arm exhibited an increase throughout the flexion range. Lengthening either the patella or the patellar ligament altered the force transmitted from the quadriceps to the patellar ligament, significantly increasing the effective moment arm at flexions greater than 25 degrees. We conclude that the levering action of the patella is an essential mechanism of knee joint operation at moderate to high flexion angles. PMID- 2914968 TI - Flow visualization of competitive swimming techniques: the tufts method. AB - The purpose of this study was to evaluate the use of tufts to visualize the flow of water around the trunk and limbs of a swimmer. Numerous pilot studies were conducted to evaluate the effectiveness of different tuft materials, dimensions and methods of attachment for recording the characteristics of the flow around a swimmer performing various strokes and drills. Differences in the patterns of flow made visible by the tufts suggested that this method of flow visualization may well be useful in resolving both basic and applied questions concerning swimming techniques. PMID- 2914969 TI - Strain-induced reorientation of an intramuscular connective tissue network: implications for passive muscle elasticity. AB - The most abundant intramuscular connective tissue component, the perimysium, of bovine M. sternomandibularis muscle was shown to be a crossed-ply arrangement of crimped collagen fibres which reorientate and decrimp on changing muscle fibre sarcomere length. Reorientation of perimysial strands was observed by light microscopy and identification of these strands as collagen fibres was confirmed by high-angle X-ray diffraction. Mean collagen fibre direction with respect to the muscle fibres ranged from approximately 80 degrees at sarcomere length = 1.1 micron to approximately 20 degrees at 3.9 microns. This behaviour was well described by a model of a crimped planar network surrounding a muscle fibre bundle of constant volume but varying length. Modelling of the mechanical properties of the perimysium at different sarcomere lengths produced a load sarcomere length curve which was in good agreement with the passive elastic properties of the muscle, especially at long sarcomere lengths. It is concluded that the role of the perimysial collagen network is to prevent over-stretching of the muscle fibre bundles. PMID- 2914970 TI - Simulation of quadrupedal locomotion using a rigid body model. AB - Locomotion of the horse is simulated using a mathematical model based on rigid body dynamics. A general method to generate the equations of motion for a two dimensional rigid body model with an arbitrary number of hinge joints is presented and a numerical solution method, restricted to tree-structured models, is described. Joint movements originating from muscular forces or moments are simulated, but the method also allows that parts of the model follow strictly the pattern of kinematic data. Moment-generators with first-order linear feedback were used as a rotational muscle-equivalent. Ground-hoof interaction forces are approximated by a viscoelastic model and pseudo-Coulomb friction in vertical and horizontal directions respectively. Results of model simulations are compared to experimentally recorded data. Subsequently, adjustments are made to improve the agreement between simulation and experimental results. PMID- 2914971 TI - Rotational and translational movement features of the pelvis and thorax during adult human locomotion. AB - The kinematics of the pelvis and thorax are important in gait studies since their movement patterns are closely related to gait efficiency and 'smoothness' of locomotion. The purpose of this study was to identify features of normal gait patterns for later comparisons with pathological and developmental gait patterns. A two camera SELSPOT system interfaced with an HP1000 minicomputer was used to obtain three-dimensional kinematic/temporal data for the pelvis and thorax. Data from treadmill walking of eight adults were used for within subject (at different speeds) analyses. The analyses revealed a very complex pattern with a set of breakpoints which was consistent over all subjects. Some features were invariant over a range of walking speeds although the total range of motion changed considerably. PMID- 2914972 TI - Effect of prosthetic mitral valve geometry and orientation on flow dynamics in a model human left ventricle. AB - Pulsatile flow dynamics through bileaflet (St Jude and Duromedics), tilting disc (Bjork-Shiley and Omniscience), caged ball (Starr-Edwards), pericardial (Edwards) and porcine (Carpentier-Edwards) mitral valves in a model human left ventricle (LV) were studied. The model human ventricle, obtained from an in situ diastolic casting, was incorporated into a mock circulatory system. Measurements were made at various heart rates and flow rates. These included the transvalvular pressure drop and regurgitation in percent and cm3 beat-1. The effect of valve geometry and the orientation of the valve with respect to the valve annulus was analyzed using a flow visualization technique. Qualitative flow visualization study indicates certain preferred orientations for the tilting disc and bileaflet valve prostheses in order to obtain a smooth washout of flow in the LV chamber. PMID- 2914973 TI - Validation of single-segment and three-segment spinal models used to represent lumbar flexion. AB - Changes in spinal posture between the erect and flexed positions were calculated using angular measurements from lateral photographs and radiographs of ten adult male subjects. For photographic measurements, the thoracolumbar vertebral column was modelled as either a single segment or as three segments. In the three segment model, there was a non-significant correlation between the decrease in lumbar concavity and intervertebral motion. In addition, there was a non significant negative correlation between the increase in thoracic convexity and lumbar motion determined radiographically. In the single-segment model, the decrease in angulation between the thoracolumbar spine and pelvis was a good representation of lumbar spine flexion as determined by the mean lumbar intervertebral angular change. Therefore, modelling the thoracolumbar vertebral column as a single segment allowed better estimation of lumbar intervertebral angular change during flexion than a three-segment model. The results indicate that large range dynamic motion of the lumbar vertebral column can be represented using photographic analysis of the positions of three easily identified anatomical landmarks: the anterior superior iliac spine, posterior superior iliac spine and the spinous process of the first thoracic vertebra. PMID- 2914974 TI - Comment on 'Multi-channel strain-gauged telemetry for orthopaedic implants'. PMID- 2914975 TI - Malignancy and joint replacement: the tip of an iceberg? PMID- 2914976 TI - The blood supply of the calcaneal tendon. AB - The microvascular anatomy of the calcaneal tendon was investigated in cadaver tendons by injection of barium sulphate and indian ink and a quantitative study of intratendinous blood supply was made, using a computer-assisted image analysis system. There was a reduction in both the number and the mean relative area of vessels in the mid-section of the tendon. This area of reduced vascularity may be of significance in the pathogenesis of rupture. PMID- 2914977 TI - Long posterior flap versus equal sagittal flaps in below-knee amputation for ischaemia. AB - We analysed the complication rate in 140 below-knee amputations in relation to surgical technique and the presence of diabetes. In all cases, the skin perfusion pressure was measured below the knee before operation to provide an objective evaluation of the microcirculation. In diabetic patients we found a significantly higher complication rate after using a long posterior flap than after equal sagittal flaps. No such difference could be demonstrated in non-diabetic patients. We suggest that the higher incidence of atherosclerotic lesions in the three major arteries below the knee in diabetic patients may account for the difference. We recommend the use of the sagittal technique for below-knee amputation in diabetic patients. PMID- 2914978 TI - Treatment of bone weakness in patients with femoral neck fracture by fluoride, calcium and vitamin D. AB - Twenty-three of 46 patients, aged 56 to 95 years, with fracture of the femoral neck (FNF) completed the first trial of 10 months treatment with oral sodium fluoride 60 mg and calcium 1800 mg on alternate days and 1 micrograms of vitamin D1 daily. Pre-treatment and post-treatment biopsy specimens and microradiographs of the iliac crest and metacarpal and spinal radiographs were evaluated together with biopsy material from seven untreated age-matched controls with FNF. In 17 patients the treatment improved the amount and quality of trabecular bone. Cortical thickness increased in nine patients and there were no losses of amount or mineralisation. The treatment was well tolerated by most patients and there were no major side-effects or signs of bone demineralisation. The study also revealed an unexpected rapid post-fracture deterioration of bone tissue in untreated FNF patients; thus there is an increased risk of further fractures which calls for the use of an effective treatment to increase bone mass. PMID- 2914979 TI - Coronal fractures of the lateral femoral condyle. AB - We reviewed seven patients with coronal fractures of the lateral femoral condyle and studied the mechanism of injury and the radiological features. The influence of soft tissue attachments on the displacement and the blood supply were investigated by clinical and cadaveric studies. All three fractures which were initially undisplaced lost position early during conservative management. Internal fixation gave good results at review, and is recommended to avoid the risk of malunion and possible secondary osteoarthritis. PMID- 2914980 TI - Lateral release for recurrent dislocation of the patella. AB - We reviewed 41 knees after arthroscopic lateral release for recurrent dislocation of the patella at a mean follow-up of four years, and graded the results according to the criteria of Crosby and Insall (1976). There were no dislocations after operation in 28 knees (68%); the less satisfactory results were in patients with subluxation of the patella on extension of the knee and those with generalised ligamentous laxity. There were no complications. A characteristic and previously unreported lesion of the patellar surface was seen in eight of the 41 knees. The results of lateral release are better than those reported for other techniques. This treatment, by either open or arthroscopic methods, is recommended. PMID- 2914981 TI - Arthroscopy under local anaesthesia. AB - Sixty patients underwent arthroscopy of the knee as day cases using a local anaesthetic technique. This provided satisfactory operating conditions and high patient acceptability. PMID- 2914982 TI - Meniscal lesions and chronic anterior cruciate ligament deficiency. Meniscal tears occurring before and after reconstruction. AB - We examined the menisci in 47 patients at the time of anterior cruciate ligament reconstruction. Twenty-one patients had abnormal menisci at a mean of 34 months after injury, but there was no difference between the Lysholm scores of patients with intact or damaged menisci. Eleven patients had a new meniscal injury between reconstruction and review at a mean of six years later; only 15 patients had both menisci intact nine years after injury. If pivot shift had been cured, the incidence of meniscal injury was reduced, but remained higher than normal. If pivot shift returned after reconstruction there was a significantly higher incidence of meniscal injury. Meniscal lesions appear to be the result of instability and not the cause. PMID- 2914983 TI - Epiphyseolysis for partial growth plate arrest. Results after four years or at maturity. AB - We reviewed 13 children with partial growth plate arrest who had been treated by epiphyseolysis. Eight were followed to skeletal maturity and five for at least four years. In three cases the affected limb was restored to normal and in five the operation was successful in improving angular deformity and leg length discrepancy such that further surgery was not necessary. In the five failures, angular deformity had progressed or limb length discrepancy had increased. There were no significant complications and the procedure did not prevent subsequent osteotomy or limb length equalisation. Epiphyseolysis was most effective for small bars and those affecting only the central area of the plate. PMID- 2914985 TI - Congenital dislocation of the hip--a misleading term: brief report. PMID- 2914984 TI - Entrapment of the superficial peroneal nerve. Diagnosis and results of decompression. AB - Entrapment of the superficial peroneal nerve was treated in 24 legs of 21 patients by fasciotomy and neurolysis; 19 of the patients were reviewed after a mean period of 37 months. Nine were satisfied with the result, another six were improved but not satisfied because of residual limitation of athletic activity, three were unchanged and one was worse. Conduction velocity in the superficial peroneal nerve had increased after operation, but the change was not significant. In five patients the nerve had an anomalous course and in 11 there were fascial defects over the lateral compartment. Chronic lateral compartment syndrome is an unusual cause of nerve entrapment. Operative decompression produces cure or improvement in three-quarters of the cases, but is less effective in athletes. PMID- 2914986 TI - An axial rotation goniometer: brief report. PMID- 2914987 TI - Embolisation for aneurysm after knee replacement: brief report. PMID- 2914988 TI - An unusual pattern of radiocarpal injury: brief report. PMID- 2914989 TI - Intraneural leiomyoma: brief report. PMID- 2914990 TI - An aid to the treatment of supracondylar fracture of the humerus: brief report. PMID- 2914991 TI - Radiology of the humeral head in recurrent anterior shoulder dislocations: brief report. PMID- 2914992 TI - A sinister bias in hip socket wear: brief report. PMID- 2914993 TI - Familial synovial chondromatosis: brief report. PMID- 2914994 TI - A method of elbow arthrodesis: brief report. PMID- 2914995 TI - Lower femoral osteotomy in cerebral palsy: brief report. PMID- 2914996 TI - Soft tissue surgery in Charcot-Marie-Tooth disease. AB - Ten patients with Charcot-Marie-Tooth disease have been reviewed at an average of 14 years after soft tissue procedures to correct foot deformities. No patient has so far required triple arthrodesis and the overall results as regards function, appearance and symptoms are satisfactory in all patients. It is concluded that soft tissue procedures can certainly postpone the need for triple arthrodesis and in many cases may obviate it altogether. PMID- 2914997 TI - The management of soft tissue sarcomas. PMID- 2914998 TI - Dynamic inversion of the forefoot and dorsiflexion of the big toe treated by transfer of extensor hallucis longus. AB - Dynamic hyperextension of the big toe and supination of the forefoot may occur in the swing phase of walking in children with various neurological disorders. Symptoms arising from this have been successfully corrected in 13 feet of 11 children by transfer of extensor hallucis longus to the insertion of peroneus brevis. PMID- 2914999 TI - Operations for forearm deformity caused by multiple osteochondromas. AB - We reviewed 36 cases of forearm deformity caused by multiple osteochondromas in 30 patients and classified them into three types: Type I showed a combination of ulnar shortening and bowing of the radius secondary to osteochondromas of the distal ulna (22 forearms). Type II showed dislocation of the radial head, either with osteochondromas of the proximal radius (Type IIa, two forearms) or secondary to more distal involvement (Type IIb, five forearms). Type III had relative radial shortening due to osteochrondromas at the distal radius (seven forearms). Operations were performed on 16 forearms in 13 patients, with 92% of satisfactory results. For Type I deformity, excision of osteochondromas, immediate ulnar lengthening and corrective osteotomy of the radius are recommended. For Type IIa, excision of the radial head is necessary, and for Type IIb, we advise gradual lengthening of the ulna using an external fixator. Excision of osteochondromas alone gave good results in Type III deformity. Our classification gives a reliable indication of the prognosis and is a guide to the choice of surgical treatment. PMID- 2915000 TI - Physeal widening in children with myelomeningocele. AB - We report five examples of physeal widening in four children with myelomeningocele. In all cases there was rapid clinical resolution with the use of the patients' normal orthoses and minor limitation of activity, and there was no evidence of early epiphyseal closure or growth disturbance. We suggest that recognition of the pathological process before fracture occurred may explain the rapid return to normal. PMID- 2915001 TI - The effect of centrifuging bone cement. AB - We have tested the porosity and fatigue life of five commonly used bone cements: Simplex P, LVC, Zimmer regular, CMW and Palacos R. Tests were conducted with and without centrifugation and with the monomer at room temperature and, except for LVC, at 0 degrees C. We found that the fatigue life of different specimens varied by a factor of nearly 100. It did not depend on porosity alone, but was more influenced by the basic composition of the cement. Simplex P when mixed with monomer at 0 degrees C and centrifuged for 60 seconds had the highest fatigue life and was still sufficiently liquid to use easily. PMID- 2915002 TI - Examining infants' hips--can it do harm? AB - Attempts to eliminate congenital dislocation of the hip by detecting it early have not been completely successful. It is not known why some infants, checked by competent examiners, still appear late with dislocations. The usual explanations of a mistake by the examiner, or of spontaneous dislocation of a hip that was stable at birth, do not explain why some centres succeed while others fail, or why good examiners may become less effective with experience. The explanation suggested is that the examination itself could be responsible and may actually cause a hip to become unstable. PMID- 2915003 TI - Pre-operative evaluation for uncemented hip arthroplasty. The role of computerised tomography. AB - We have studied the role of computerised axial tomography in the assessment of the acetabulum before an uncemented Mittelmeier arthroplasty was performed in 20 patients. In the absence of gross anatomical abnormality, computerised tomography did not provide additional information, but in eight patients it was useful in determining adequacy of acetabular depth, anterior acetabular cover, and thickness of the anterior and posterior walls. In these patients, the CT scans provided information which was not available from plain radiographs and greatly assisted in pre-operative planning. PMID- 2915004 TI - Abductor function after total hip replacement. An electromyographic and clinical review. AB - Electromyographic and clinical studies were performed on patients undergoing total hip replacement by the modified direct lateral (29 hips), the direct lateral (29 hips) and the posterior approaches (21 hips). Assessments were made three months after operation. The Trendelenburg test was positive (Grade II) in eight cases operated upon by the direct lateral route, but in only one of each of the other two groups. Denervation occurred in only five of the 28 hips with abductor weakness without statistical difference between the groups. In the modified direct lateral group, radiological evidence of union of the trochanteric sliver was associated with significantly better abductor function than in those with malunion or non-union. PMID- 2915005 TI - Total knee arthroplasty in the patient with Parkinson's disease. AB - We have reviewed nine patients with Parkinson's disease who had 12 primary total knee arthroplasties and one revision. Deformities were corrected by conventional techniques and semi-constrained resurfacing arthroplasties were used. Follow-up ranged from two to eight years (average 4.3 years). Nine of the 12 primary arthroplasties were rated as excellent by the Hospital for Special Surgery knee score system, and three were rated as good. Contrary to previous reports, we feel that total knee arthroplasty performed on patients with Parkinson's disease, is a highly satisfactory procedure, alleviating knee pain and improving function. PMID- 2915006 TI - Freezing of orthopaedic specimens before mechanical testing. AB - The effect of storage at sub-zero temperatures and subsequent thawing was investigated in dissected muscles, tendons, limbs and spines. Freezing caused a noticeable shortening of muscles which when thawed could easily be elongated; the same effects, though less pronounced, were observed with tendons. During freezing, myotomy or tenotomy led to the development of a striking deformity owing to unopposed shortening of the opposing muscles. After thawing, all frozen specimens containing muscles and joints showed an increased range of passive movements, easily demonstrable by mild tensile forces. PMID- 2915007 TI - Reliability of radiological measurements in the assessment of the child's hip. AB - We investigated the reproducibility of the various radiological methods of assessment of hip dysplasia by making 474 assessments of hips and quantifying the inter-observer and intra-observer variation. There was a wide range of variability between the readings made by different observers and by one observer on two occasions. A measurement of acetabular index has to be given a range of +/ 6 degrees in order to be 95% confident of including the true measurement. We found the most helpful measurements to be the acetabular index, up to the age of eight years; the centre-edge angle, over the age of five years; and Smith's c/b ratio and neck-shaft angle. We feel, however, that the change in value over a series of radiographs in the same child is much more valuable. Single readings of all the radiological measurements investigated in this study were unreliable. PMID- 2915008 TI - Operation for old sternoclavicular dislocation. Results in 12 cases. AB - Twelve patients were operated upon after unsuccessful conservative treatment for complete dislocation of the sternoclavicular joint. Three methods were used; stabilisation using fascial loops, reconstruction with a tendon graft, and resection of the sternal end of the clavicle. The results were good in only four patients, three treated with a tendon graft and one by fascial loops. Another four patients had fair results, but all four treated by resection of the medial end of the clavicle had poor results, with pain and weakness of the upper extremity. In our opinion resection of the sternal end of the clavicle should not be used in old traumatic dislocation. PMID- 2915009 TI - Closed reduction of fractures of the proximal radius in children. AB - We present a method for the reducing a displaced radial head in children, by rotating the forearm while pressing over the displaced fragment. This has been successful in a series of 10 cases. PMID- 2915010 TI - External fixation or plaster for severely displaced comminuted Colles' fractures? A prospective study of anatomical and functional results. AB - We report a prospective, randomised, controlled trial of 50 severely displaced comminuted Colles' fractures treated by either external fixation or manipulation and plaster. Each patient was assessed radiographically throughout treatment, and functionally by an independent observer at three and six months. The functional result correlated with the anatomical result, which was significantly better in patients treated by external fixation. This resulted in significantly improved function especially in young patients, and also a lower complication rate. We recommend the use of external fixation for young patients with comminuted displaced Colles' fractures unless manipulation and plaster show excellent reduction. PMID- 2915011 TI - Repair of rabbit articular surfaces with allograft chondrocytes embedded in collagen gel. AB - In an attempt to repair articular cartilage, allograft articular chondrocytes embedded in collagen gel, were transplanted into full-thickness defects in rabbit articular cartilage. Twenty-four weeks after the transplantation, the defects were filled with hyaline cartilage, specifically synthesising Type II collagen. These chondrocytes were autoradiographically proven to have originated from the transplanted grafts. Assessed histologically the success rate was about 80%, a marked improvement over the results reported in previous studies on chondrocyte transplantation without collagen gel. By contrast, the defects without chondrocyte transplantation healed with fibrocartilage. Immunological enhancement induced by transplanted allogenic chondrocytes or collagen was not significant at eight weeks after treatment, so far as shown by both direct and indirect blastformation reactions. Thus, allogenic transplantation of isolated chondrocytes embedded in collagen gel appears to be one of the most promising methods for the restoration of articular cartilage. PMID- 2915012 TI - Anterior approach to the upper thoracic vertebrae. AB - The anterior exposure of the upper thoracic spine using standard methods is often difficult and limited. We report our experience using a technique described by Sundaresan et al. (1984) in which the medial portion of one clavicle and part of the manubrium sterni are excised. In 10 cases we found this to be a useful and safe procedure. PMID- 2915013 TI - Ipsilateral sciatica on femoral nerve stretch test is pathognomonic of an L4/5 disc protrusion. AB - The straight leg raising test and the femoral nerve stretch test exert traction on the sciatic and femoral nerve, and the lumbosacral plexus and roots. In 40 patients with a suspected L4/5 disc protrusion, ipsilateral sciatica was induced by the femoral nerve stretch test. We believe that this is a pathognomonic sign of a lateral protrusion at L4/5 level. PMID- 2915014 TI - Diagnosis of acute atlanto-axial rotatory fixation. AB - We report three cases of atlanto-axial rotatory fixation in adults. Early diagnosis was made by clinical tests showing restricted head rotation in maximal neck flexion and asymmetry of the transverse processes of the atlas, confirmed by cineradiography. Early treatment by traction may obviate long-term problems of torticollis and instability. PMID- 2915015 TI - Does sublaminar wiring produce spinal stenosis? AB - Sublaminar wiring provides strong and effective fixation of the scoliotic or unstable spine, but its long-term effects on the spinal canal remain unknown. An animal model was developed to observe these effects on the growth and development of the immature spine over a two-year period. Laminar overgrowth occurred both longitudinally to produce a kyphoscoliosis and in the transverse plane to cause significant laminar thickening and growth into the spinal canal. However, the cross-sectional area of the spinal canal was not significantly compromised. PMID- 2915016 TI - The axis of rotation of the ankle joint. AB - The axis of the talo-crural joint was analysed by roentgen stereophotogrammetry in eight healthy volunteers. Examinations were performed at 10 degrees increments of flexion and pronation/supination of the foot as well as medial and lateral rotation of the leg. Results indicate that the talo-crural joint axis changes continuously throughout the range of movement. In dorsiflexion it tended to be oblique downward and laterally. In rotation of the leg, the axis took varying inclinations between horizontal and vertical. All axes in each subject lay close to the midpoint of a line between the tips of the malleoli. Our study indicates that the talo-crural joint axis may alter considerably during the arc of motion and differ significantly between individuals. This prompts caution in the use of hinge axes in orthoses and prostheses for the ankle. PMID- 2915017 TI - Capnocytophaga canimorsus sp. nov. (formerly CDC group DF-2), a cause of septicemia following dog bite, and C. cynodegmi sp. nov., a cause of localized wound infection following dog bite. AB - CDC group DF-2 is the vernacular name given to a slow-growing gram-negative bacterium that causes septicemia and meningitis in humans. Infections frequently (one-third of cases) occur following dog bites or close contact with dogs or occasionally with cats. Splenectomy and alcoholism appear to be strong predisposing factors for DF-2 infection. In addition to 150 DF-2 strains received for identification, we received 9 DF-2-like strains; 6 were isolated from wound or eye infections, 3 of which were associated with dog bites and 1 of which was associated with a cat scratch, and 3 were isolated from dog mouths. The major characteristics of DF-2 include production of acid but no gas from lactose and maltose and usually D-glucose; positive reactions for oxidase, catalase, arginine dihydrolase, gliding motility, and o-nitrophenyl-beta-D-galactopyranoside; growth enhanced by serum and by incubation in a candle jar atmosphere; and negative reactions for sucrose, raffinose, inulin, melibiose, nitrate reduction, indole, and growth on MacConkey agar. DF-2-like strains had the same characteristics, except that acid was formed from sucrose, raffinose, inulin, and melibiose. By the hydroxyapatite method, DNAs from 12 DF-2 strains were 88% related in 60 degrees C reactions and 84% related in 75 degrees C reactions. Related sequences contained 0.5 to 1.5% unpaired bases (divergence). Three DF-2-like strains were 73 to 80% related at 60 degrees C (with 2.0 to 2.5% divergence) and 68 to 75% related at 75 degrees C. The relatedness of DF-2 and DF-2-like strains was 19 to 31% at 60 degrees Celsius and 13 to 19% at 75 degrees Celsius. The relatedness of DF-2 and DF-2-like strains to Capnocytophaga species was 4 to 7%. The DNA relatedness date indicate that eh DF-2 and the DF-2-like strains are separate, previously undescribed species. Both groups are phenotypically and genetically distinct from Capnocytophaga species, although they do share several characteristics with Capnocytophaga species, including cellular morphology, gliding motility, cellular fatty acid composition, enhancement of growth in a candle jar atmosphere, and G+C content. The new species differ from Capnocytophaga species by their positive oxidase and catalase reactions. We chose to avoid creating a new genus and proposed the names Capnocytophaga canimorsus sp. nov. for group DF-2 and C. cynodegmi sp. nov. for the DF-2-like strains. PMID- 2915018 TI - Use of a cutoff range in identifying mycobacteria by the Gen-Probe Rapid Diagnostic System. AB - Commercial DNA probes (Gen-Probe Corp., San Diego, Calif.) for Mycobacterium tuberculosis complex Mycobacterium avium, and Mycobacterium intracellulare were compared with conventional methods for accuracy, applicability, and speed for the identification of putative isolates of the M. tuberculosis and M. avium complexes. Results are expressed as percent hybridization. Values of greater than 15% were considered positive, and values of less than 5% were negative. Cultures having hybridization values within an indeterminate range of 5 to 15% were repeated. Mycobacterial isolates resembling M. tuberculosis and M. avium complex from cultures of 589 specimens, representing 432 patients, were entered into this study; 294 cultures were tested with the M. tuberculosis complex probe, and 326 cultures were tested with the M. avium probe. In all cases, probe results agreed with our biochemical identification of the isolates. The M. intracellulare probe was used with 117 isolates morphologically resembling M. avium complex, and one false-negative result was observed. Seventy-two cultures gave initial hybridization results that fell within the indeterminate range and were repeated. If the manufacturer's recommended 10% cutoff value had been used, the original hybridization values would have resulted in 27 misidentified cultures, 16 false negatives and 11 false-positives. PMID- 2915019 TI - Prevalence of hydrogen peroxide-producing Lactobacillus species in normal women and women with bacterial vaginosis. AB - A predominance of Lactobacillus species in the vaginal flora is considered normal. In women with bacterial vaginosis, the prevalence and concentrations of intravaginal Gardnerella vaginalis and anaerobes are increased, whereas the prevalence of intravaginal Lactobacillus species is decreased. Because some lactobacilli are known to produce hydrogen peroxide (H2O2), which can be toxic to organisms that produce little or no H2O2-scavenging enzymes (e.g., catalase), we postulated that an absence of H2O2-producing Lactobacillus species could allow an overgrowth of catalase-negative organisms, such as those found among women with bacterial vaginosis. In this study, H2O2-producing facultative Lactobacillus species were found in the vaginas of 27 (96%) of 28 normal women and 4 (6%) of 67 women with bacterial vaginosis (P less than 0.001). Anaerobic Lactobacillus species (which do not produce hydrogen peroxide) were isolated from 24 (36%) of 67 women with bacterial vaginosis and 1 (4%) of 28 normal women (P less than 0.001). The production of H2O2 by Lactobacillus species may represent a nonspecific antimicrobial defense mechanism of the normal vaginal ecosystem. PMID- 2915020 TI - Recovery of Pseudomonas gladioli from respiratory tract specimens of patients with cystic fibrosis. AB - Pseudomonas gladioli was isolated from 11 patients with cystic fibrosis. It resembled Pseudomonas cepacia on the selective and differential medium OFPBL, producing yellow colonies after 48 to 72 h of incubation. Isolates were characterized biochemically, by DNA hybridization, and by cellular fatty acid analysis. A review of the clinical status of selected patients colonized by P. gladioli did not reveal any apparent association of this organism with infectious complications of cystic fibrosis. Thus, the clinical implications may differ depending on which of these two closely related species is reported by laboratories. Determination of the fatty acid profile of isolates by gas chromatography may be a useful adjunct to biochemical characterization as a means of identification. In contrast to P. cepacia, most isolates of P. gladioli contained 3-OH C10:0 fatty acid under the growth conditions used. PMID- 2915021 TI - Detection and quantitation of Anaplasma marginale in carrier cattle by using a nucleic acid probe. AB - Cattle which have recovered from acute infection with Anaplasma marginale, a rickettsial hemoparasite of cattle, frequently remain persistently infected with a low-level parasitemia and serve as reservoirs for disease transmission. To fully understand the role of these carriers in disease prevalence and transmission, it is essential that low levels of parasitemia can be accurately detected and quantitated. We have developed a nucleic acid probe, derived from a portion of a gene encoding a 105,000-molecular-weight surface protein, that can detect A. marginale-infected erythrocytes. The probe is specific for A. marginale and can detect 0.01 ng of genomic DNA and 500 to 1,000 infected erythrocytes in 0.5 ml of blood, which is equivalent to a parasitemia of 0.000025%. This makes the probe at least 4,000 times more sensitive than light microscopy. Hybridization of the probe with treated blood from animals proven to be carriers of anaplasmosis showed that parasitemia levels were highly variable among carriers, ranging from greater than 0.0025 to less than 0.000025%. Parasitemia levels of individual animals on different dates were also variable. These results imply that, at any given time, individuals within a group of cattle may differ significantly in their abilities to transmit disease. PMID- 2915022 TI - Respiratory syncytial virus-specific antibody responses in immunoglobulin A and E isotypes to the F and G proteins and to intact virus after natural infection. AB - We studied the antibody response to the fusion (F) and attachment (G) proteins of respiratory syncytial virus and to purified intact virus in the respiratory secretions of 29 infants and children. The goal of the study was to determine whether the immune response to either of the glycoproteins occurred predominantly in the immunoglobulin A (IgA) as opposed to the IgE isotype, which would indicate that one protein subunit would be a better candidate as a potential vaccine. Antibody responses were determined by using an enzyme-linked immunosorbent assay with purified F and G proteins and sucrose gradient-purified intact virus as targets. Infants and children were capable of developing an antibody response in both the IgA and IgE isotypes to each target antigen. The magnitude of the antibody response to the F protein was essentially similar to that to the intact virus, while responses to the G protein were diminished in infants. A slightly more favorable ratio of IgA to IgE responses was observed against the F protein in comparison to the G protein. While neither protein subunit had the ideal characteristics of inducing an IgA response in the absence of an IgE response, the F protein seems to be a better candidate for use as a vaccine, on the basis of better IgA/IgE ratios. PMID- 2915023 TI - Immunoblot analysis of antibody responses to Sporothrix schenckii. AB - The serologic response to Sporothrix schenckii was investigated in patients with sporotrichosis by solid-phase enzyme-linked immunosorbent assays (ELISAs) and Western immunoblot techniques. A soluble antigen preparation derived from an S. schenckii isolate contained 15 protein staining components ranging in molecular size from 22 to 70 kilodaltons (kDa) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Sera from 40 patients with sporotrichosis demonstrated Sporothrix immunoglobulin G antibody by ELISA with titers between 128 and 65,200. No sera from 300 healthy individuals or 100 patients with various systemic mycoses other than sporotrichosis had ELISA titers greater than 64. By Western immunoblotting of the antigens separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, sera from 10 patients with cutaneous sporotrichosis reacted with 8 to 10 antigen components (range, 40 to 70 kDa), while sera from 15 patients with extracutaneous sporotrichosis reacted with a greater number of antigen components (15 to 20 bands) over a wider range of molecular sizes (22 to 70 kDa). Antibody to 40- and 70-kDa antigen components was detected by immunoblots in all sera tested from patients with sporotrichosis. Antibody to 22- to 36-kDa antigen components was present in sera from 13 of 15 patients with extracutaneous sporotrichosis, but these lower-molecular-weight components were not detected by sera from patients with cutaneous sporotrichosis. Antibody to these components was not detected by Western blotting in sera from 19 of 20 patients with other fungal diseases or from 30 healthy individuals. Purification of these specific antigen fractions could provide the basis of a sensitive and specific serodiagnostic test to indicate the presence and activity of extracutaneous sporotrichosis. PMID- 2915024 TI - Bacteremia with Streptococcus bovis and Streptococcus salivarius: clinical correlates of more accurate identification of isolates. AB - Two biotypes of Streptococcus bovis can be identified by laboratory testing and can be distinguished from the phenotypically similar organism Streptococcus salivarius. We assessed the clinical relevance of careful identification of these organisms in 68 patients with streptococcal bacteremia caused by these similar species. S. bovis was more likely to be clinically significant when isolated from blood (89%) than was S. salivarius (23%). There was a striking association between S. bovis I bacteremia and underlying endocarditis (94%) compared with that of S. bovis II bacteremia (18%). Bacteremia with S. bovis I was also highly correlated with an underlying colonic neoplasm (71% of patients overall, 100% of those with thorough colonic examinations) compared with bacteremia due to S. bovis II or S. salivarius (17% overall, 25% of patients with thorough colonic examinations). We conclude that careful identification of streptococcal bacteremic isolates as S. bovis biotype I provides clinically important information and should be more widely applied. PMID- 2915025 TI - Rapid detection of group C streptococci from animals by latex agglutination. AB - A group C latex agglutination reagent, included as the negative control in the PathoDx Strep A latex agglutination test (Diagnostic Products Corp., Los Angeles, Calif), was compared with culture for rapid detection of group C streptococci (Streptococcus equi, S. equisimilis, S. zooepidemicus, and S. dysgalactiae) from swabs of veterinary specimens. The overall sensitivity of the latex test was 78%, and specificity was 97.6%. Only 25% of S. dysgalactiae isolates were detected, thereby accounting for the relatively low sensitivity. Ninety-three percent of the group C streptococci other than S. dysgalactiae were isolated from horses. When the latex test was evaluated for detection of group C streptococci other than S. dysgalactiae from horses, the sensitivity and specificity were 95.3 and 100%, respectively. We found the group C latex agglutination test to be a rapid and accurate method for the detection of the major pathogenic group C streptococci from swabs of equine specimens. PMID- 2915026 TI - Clonal nature of Salmonella typhi and its genetic relatedness to other salmonellae as shown by multilocus enzyme electrophoresis, and proposal of Salmonella bongori comb. nov. AB - Crude cell extracts of 26 isolates of Salmonella serotype typhi (S. typhi) and 48 other Salmonella isolates representing 28 serotypes and seven DNA hybridization subgroups were analyzed for electrophoretic variants of 24 metabolic enzymes by starch gel electrophoresis. All strains of S. typhi had identical isoenzyme patterns, indicating that they were a single clone. All of the enzymes detected in the remaining strains were polymorphic, and the degree of genetic variation was quite high. The average number of alleles per enzyme locus was 4.7, and the mean genetic diversity per locus was 0.556. Thirty-two distinct allele profiles, or electrophoretic types (ETs), were found in these 48 strains of Salmonella serotypes other than S. typhi. Analysis of the genetic relationships of the ETs to each other showed that, with one exception, the ETs formed subgroups that were consistent with the subgroupings based on DNA hybridization studies. ET profiles were not always linked to specific serologic patterns. These data show that multilocus enzyme electrophoresis has a potential application in epidemiologic and taxonomic studies of salmonellae, although it is not differential for S. typhi. We also propose a new species, Salmonella bongori comb. nov., a new combination base on the elevation of Salmonella choleraesuis subsp. bongori to the level of species. PMID- 2915027 TI - Identification and classification of Campylobacter strains by using nonradioactive DNA probes. AB - Acetylaminofluorene-labeled genomic DNA probes were used for the identification and classification of Campylobacter strains. Relationships among 17 well-known strains of Campylobacter species and subspecies were studied by comparing acetylaminofluorene- or 32P-labeled probes. Results obtained with both methods were closely correlated and were in agreement with those already reported. In an identification experiment, hybridization with nonradioactive probes was performed on 60 strains isolated from stool samples after subculturing and quick DNA extraction; conventional biochemical tests were conducted in parallel. A good correlation was found between the results obtained by nonradioactive hybridization and by biochemical tests. Thus, the acetylaminofluorene-labeled genomic DNA probe method is an interesting alternative for laboratories without access to radioisotopes for the identification and classification of bacteria. PMID- 2915028 TI - Identification of Campylobacter pylori by using the rapID NH system. AB - Campylobacter pylori has been associated with chronic active antral gastritis. The organism was isolated from 19 of 45 gastric mucosal biopsies on blood agar plates with increased CO2 at 35 degrees C. The RapID NH system, a set of dehydrated substrates for preformed enzymes, was used to assist in the identification of C. pylori. All C. pylori gave the same biochemical profile, and it was different from those of all other organisms in the profile index of the manufacturer. The RapID NH system is useful in the identification of C. pylori. PMID- 2915029 TI - Corynebacterium aquaticum urinary tract infection in a neonate, and concepts regarding the role of the organism as a neonatal pathogen. AB - Corynebacterium aquaticum urinary tract infection developed in a neonate 8 days after uncomplicated vaginal delivery. Prior to definitive identification, the isolate was thought to be Listeria monocytogenes because of its microscopic morphology, catalase positivity, and tumbling motility. The infant responded to intravenous ceftriaxone. Because the presentation of C. aquaticum in this patient suggested systemic involvement, C. aquaticum may be regarded as a bona fide neonatal pathogen. PMID- 2915030 TI - Growth of Aeromonas spp. on Butzler Campylobacter selective agar and evaluation of the agar for the primary isolation of Aeromonas spp. from clinical specimens. AB - The fortuitous finding that Aeromonas spp. grew well on Butzler Campylobacter selective medium (BCSA) in a microaerobic atmosphere at 42 degrees C prompted us to evaluate the performance of BCSA for selective isolation of aeromonads in comparison with ampicillin (30 micrograms/ml) sheep blood agar (ASBA30). Overall recovery rates of aeromonads from 563 stool samples from patients with acute diarrhea were higher on ASBA30 (70.4%) than on BCSA (56.3%); however, 21 (29.5%) grew only on BCSA. The three human-associated Aeromonas spp. could be recovered on BCSA and ASBA30. We recommend the use of BCSA to laboratories reluctant to include a specific selective medium for aeromonads. PMID- 2915031 TI - Functional topography during sensorimotor activation studied with event-related desynchronization mapping. AB - Event-related desynchronization (ERD) of alpha components was studied in four subjects during self-paced voluntary movements and somatosensory stimulation. EEG was recorded from 29 electrodes with a common right ear reference; local average reference derivations were calculated and used for computing ERD maps at 250-ms intervals. It was found that upper alpha components were desynchronized close to electrodes C3 and C4 overlying the primary sensorimotor cortex during voluntary movements and somatosensory stimulation. ERD started contralaterally more than 2 s before the movement and some hundreds of milliseconds before the stimulation. During the performance of unilateral movement and unilateral stimulation, ERD was bilaterally symmetric. Desynchronization of lower alpha components was found over the superior parietal cortex, clearly starting some hundreds of milliseconds after the desynchronization of upper frequency components. Therefore, the desynchronization of lower and upper alpha components reflects activation of different neuronal structures. PMID- 2915032 TI - Combined adductor transfer, iliopsoas release, and proximal hamstring release in cerebral palsy. AB - Twenty-two patients with cerebral palsy (CP) and progressive lateral migration of the hip who underwent a combined adductor transfer, iliopsoas release, and proximal hamstring release were reviewed retrospectively. The average age at surgery was 4 years 9 months, and clinical and roentgenographic follow-up averaged 21.9 and 19.2 months, respectively. Ninety-five percent of the patients demonstrated an improved range of motion. Roentgenographic analysis showed a statistically significant decrease in the migration percentage and the acetabular angle and an increase in the CE angle. We concluded that this procedure adequately addressed this complex problem, thereby limiting the number of hospitalizations and surgical procedures for this patient group. Longer follow-up will be necessary to determine if these results are maintained with time. PMID- 2915033 TI - Magnetic resonance imaging in early diagnosis of Legg-Calve-Perthes disease. AB - Two male patients, aged 6 and 9 years, were suspected of having unilateral Perthes disease because of typical symptoms and clinical signs. Roentgenograms, including scintigraphy, were normal. Magnetic resonance imaging (MRI) showed definite avascular necrosis in the affected hip. Roentgenograms subsequently also became positive for Perthes disease. These two cases document the advantages of MRI in early diagnosis of Perthes disease prior to development of typical radiologic changes. PMID- 2915034 TI - Wrist pain and distal growth plate closure of the radius in gymnasts. AB - Three cases in which wrist pain developed in skeletally immature competitive gymnasts are presented. In all three cases there is radiographic evidence of premature growth plate closure, resulting in shortening of the radius and alterations in the normal distal radioulnar articulation. Repetitive compressive loading of the distal growth plate of the radius is proposed as a potential etiology of this condition. Treatment goals, including an example of successful ulnar shortening, are reviewed. The authors suggest activity limitation with the onset of symptoms, in order to avoid the permanent structural changes observed in our patients. PMID- 2915035 TI - Management of femoral shaft fractures in the adolescent. AB - Forty-four patients (45 fractures) with open physes (age range 11-16 years) underwent treatment for femoral shaft fractures. Seven malunions occurred in the 24 fractures in the nonoperative group; none occurred in the 21 fractures treated by intramedullary nailing. Hospital stay was significantly shorter in the operatively treated patients. There was no premature growth arrest in the surgical group. PMID- 2915036 TI - The effect of limping on vertebral bone density: a study of children with tarsal coalition. AB - To determine whether limping is associated with decreased bone mineralization, the trabecular and integral bone densities (BDs) of 18 Caucasian children exhibiting computed tomographic evidence of tarsal coalition (14 boys, 4 girls, aged 9 years, 5 months to 16 years, 3 months) were compared with those of an age- and sex-matched control group. Patients with tarsal coalition had significantly lower trabecular (p less than 0.05) and integral (p less than 0.05) BD than controls. Trabecular spinal density was approximately 17% lower on the average in patients with tarsal coalition. Among the limping patients, neither the duration of symptoms nor bilaterality was associated with decreased BD. The findings suggest that painful tarsal coalition may decrease vertebral bone mass and predispose to spinal osteoporosis. PMID- 2915037 TI - Remodeling potential of long bones following angular osteotomies. AB - The radius and tibia of an immature monkey remodeled 5 degrees/year until maturity after osteotomies. The periosteum and the growth plate contributed equally to the correction. Valgus, varus, and flexion deformities corrected to the same degree. Epiphysiodesis of the adjacent growth plates did not prevent correction of the shaft. Remodeling at the osteotomy site was characterized radiographically by bone deposition on the concave side but no significant resorption on the convex side. PMID- 2915038 TI - Correction of idiopathic clubfoot: a comparison of results of early versus delayed posteromedial release. AB - The clinical and radiographic results of posteromedial release performed on 30 patients (44 feet) were assessed. The patients were divided into three groups based on their average age at the time of operation (early, 4.4 months; middle, 9.1 months; and late, 16.1 months). All patients had similar preoperative deformity, surgical management, and postoperative treatment. The outcomes of all three groups were similar with the exception of hindfoot-to-forefoot alignment and hindfoot varus correction. The early group demonstrated better clinical and radiologic foot alignment and had the lowest incidence of radiologic tarsal deformities (7 vs. 28% in the middle group and 35% in the late group). PMID- 2915039 TI - Comparative review of surgical treatment of the idiopathic clubfoot by three different procedures at Columbus Children's Hospital. AB - Ninety-nine feet in 54 children were both clinically and roentgenographically evaluated following one of three different procedures of soft tissue clubfoot release. A new rating system that weights dynamic functional results more heavily was used to compare results. Roentgenographic complications included both over- and undercorrection at the talonavicular articulation, avascular necrosis of the talus, navicular, and calcaneus, and talar dome flattening. Recommendations concerning technical aspects of operative approach to clubfeet include (a) more physiologic orientation of the bimalleolar axis, (b) anatomic alignment at the talonavicular joint, and (c) use of the hinged ankle cast brace to increase final ankle range of motion (ROM). PMID- 2915040 TI - Congenital generalized fibromatosis with predominant osseous involvement in a Chinese newborn. AB - A rare case of congenital generalized fibromatosis with predominant bone involvement in a Chinese newborn is reported. Radiological examination revealed multiple osteolytic lesions in all the long limb bones and the skull. Pathology showed a mixture of fibroblasts and smooth muscle-like cells. The spontaneous regression of most of the bone lesions after 18 months is highlighted. PMID- 2915041 TI - Deep volar compartment syndrome of the forearm following minor crush injury. AB - The case of an 11-year-old boy with an ischemic contracture of the forearm and hand, initiated by a minor injury, is reported. Awareness of the syndrome, careful examination, and observation are emphasized. The decompression must include opening of all the tight fascial envelopes. PMID- 2915042 TI - Intramuscular hemangioma in infancy: diagnostic and therapeutic considerations. AB - Two cases of intramuscular hemangioma occurring in infancy are reported. These lesions require skillful preoperative evaluation, as they must be differentiated from soft tissue malignancies. If possible, surgical treatment should be delayed to a later age. PMID- 2915043 TI - A new method of intra-oral open reduction using a screw applied through the mandibular crest of condylar fractures. AB - As a result of dry skull morphometry on 50 mandibles, the author has obtained evidence that the mandibular crest, the protuberance between the retromolar trigone and the condylar process, was the thickest portion of the ascending ramus of the mandible. This anatomical structure is available for osteosynthesis of condylar fractures when an appropriate surgical procedure is developed and applied. In this paper, a new intra-oral approach technique is presented which is devised for osteosynthesis of condylar fractures using a cancellous bone screw primarily applied through the mandibular crest. PMID- 2915044 TI - Treatment of mandibular fractures. Need for rigid internal fixation. AB - The treatment of 200 mandibular fractures was evaluated retrospectively with special reference to the need for rigid internal fixation (AO-plating), as indicated by the ASIF organization. It was shown that the treatment was most typically intermaxillary fixation (50%) followed by Gunning-type splints (17%), wire (16%) and plate (6%) osteosynthesis, while 11% received no active treatment. Complications during splinting were most common among patients treated by osteosynthesis via an extra-oral approach. Most of the fractures (73%) were estimated to be anatomically suitable for AO-plating. One fifth (22%) had relative indications for the use of rigid internal fixation, and 59% had absolute indications, mostly due to simultaneous condylar and corpus (body) fractures or due to fractures in the angle region. PMID- 2915046 TI - Extra-articular ankylosis of the coronoid processes to the base of the skull. A case report. AB - Extra-articular temporomandibular bony ankylosis between the coronoid process and the base of the skull is quite uncommon. In this paper we present a case of fusion of the right coronoid to the maxilla and sphenoid bone in an 18-year-old male. This bony ankylosis was the result of surgical removal of an odontogenic tumour from the right mandibular ramus when the patient was 4 years old. The ankylosis of the right coronoid resulted in hypoplasia of the mandible and fibrous fusion between the left coronoid and the base of the skull. The patient was treated by bilateral operation. Postoperative recurrent dislocation of the left condyle was attributed mainly to unbalanced muscle activity and to the flattening of the articular eminence of the left temporomandibular joint which had developed during the long duration of the ankylosis. This was successfully treated by left condylectomy. PMID- 2915045 TI - Use of a miniplate to provide intermaxillary fixation in the edentulous patient. AB - A case of severe facial trauma is presented. The fractures were stabilized using wire osteosynthesis and miniplates. Since no dentures were available intermaxillary fixation was achieved with a miniplate from the upper to the lower jaw, which resulted in a very satisfactory stabilization. PMID- 2915047 TI - Placement of a porous membrane underneath the mucoperiosteal flap and its effect on periodontal wound healing in dogs. AB - This study was designed to investigate the healing of surgically induced, horizontal periodontal defects in dogs following placement of a biocompatible, porous polytetrafluorethylene membrane around the roots of the treated teeth and to compare the healing to that of control teeth without membrane. Mandibular premolar teeth of 5 beagle dogs were used for experimentation. Specimen blocks were removed 3 months postoperatively for histological evaluation of contralateral experimental and control teeth. Mean apical migration of junctional epithelium among the experimental surfaces amounted to 0.1 mm as compared to 1.3 mm for the control surfaces. Accordingly, the amount of connective tissue attachment, defined by the distance from the base of the junctional epithelium to the apical termination of root planing, was greater for experimental than for control surfaces. As this increased amount of connective tissue attachment was associated with more coronal bone apposition, a periodontal ligament space was more prevalent in experimental than in control surfaces. A limited amount of ankylosis was observed for both experimental and control surfaces. Root resorption was more prevalent in control than in experimental surfaces. Conceivable reasons for the differences in healing between experimental and control teeth are discussed. PMID- 2915048 TI - Histological evaluation of periodontal probe penetration in untreated facial molar furcations. AB - The purpose of this investigation was to histologically determine the position of the periodontal probe tip when probing the deepest interradicular pocket depth in grade II and III facial molar furcation sites. Facial furcation pockets (5.8 mm +/- 1.3) were probed with a pressure-sensitive probe set at 50 g pressure. The probe tip was attached to the tooth with an acid etched composite resin. Surgical block biopsies were removed, fixed, decalcified and processed for histological sectioning. Buccolingual serial sections (6 mu) were cut from 9 biopsies and apicocoronal serial sections were cut from 3 biopsies. The sections were histometrically analyzed. The probe tip penetrated the inflamed furcation connective tissue an average depth of 2.1 mm (+/- 0.6). The probe tip was located 0.4 mm (+/- 1.4) apical to the crest of the interradicular bone. The % of inflammatory cell infiltrate in the connective tissue (ICT) around the probe tip was 56% (+/- 15%). There was no correlation between the % of ICT and the depth of probe penetration. This investigation demonstrated that probing of untreated facial molar furcation sites does not measure the attachment level of the interradicular root surfaces, but rather records the depth of probe penetration into the inflamed furcation connective tissue. PMID- 2915049 TI - Treatment of recurrent periodontal disease by root planing and Ornidazole (Tiberal). Clinical and microbiological findings. AB - The purpose of this study was to evaluate the use of Ornidazole as an adjunct to root planing in the therapy of patients suffering from recurrent periodontal disease. In 10 individuals who had previously been treated with scaling, root planing and periodontal surgery and who had followed a regular maintenance program including recall visits every 3-5 months for 1-7 years, 2 sites with recurrent periodontitis and 1 shallow site were selected. Reinfected sites had a record of losing clinical attachment of more than 3 mm since the completion of initial therapy, were bleeding upon probing and had a mean pocket probing depth of 7.85 +/- 1.31 mm. They had been reinstrumented several times by a registered dental hygienist, when clinical signs of recurrence of disease had appeared and the root surfaces were judged to be smooth and free of deposits. Clinical parameters were recorded and microbial samples were collected twice prior to retreatment. Then, 500 mg Ornidazole, to be taken twice a day for 10 days, was administered, and the whole dentition was thoroughly scaled and root planed. At day 10 as well as 2, 5, 8 and 11 months thereafter, samples were again obtained. At baseline, reinfected sites showed over 20% spirochetes, over 20% motile rods and over 9% fusiform organisms in darkfield preparations of subgingival plaque samples. Culturally, over 1/10 of organisms were identified as black pigmenting Bacteroides and in 18% of all baseline samples collected, B. gingivalis was found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2915050 TI - Computer-assisted densitometric image analysis (CADIA) for the assessment of alveolar bone density changes in furcations. AB - The purpose of this study was to test the applicability of computer-assisted densitometric image analysis (CADIA) for the quantitative assessment of alveolar bone density changes in furcations of multirooted teeth. In 21 patients, standardized radiographs were obtained immediately after and at 1, 6 and 12 months after periodontal flap procedures. Digitized images were obtained by means of a video-camera combined with an image processor that was linked to a computer. Quantitative information regarding density changes within windows covering furcation areas was obtained after superimposition and grey-level correction of images to be compared. 1 month after flap reflection, significantly more density loss was obtained in test furcations exposed to periodontal surgery, compared to the density changes in control furcation exposed to scaling and root planing. At 12 months, however, significantly greater increase in density was measured in test furcations compared to the 1-month results. The radiographic data were compared to the clinical parameters. In test furcations, there was a negative correlation of r = -0.52 between the GI and the loss in density at 1 month, and a negative correlation of r = -0.61 between the loss in density at 6 months and the probing attachment level at 12 months. These results indicate that CADIA may give valuable additional diagnostic information regarding alveolar bone density changes in furcations in studies on periodontal therapy. PMID- 2915051 TI - Relative stability of deep- versus shallow-side bone levels in angular proximal infrabony defects. AB - The relative changes with time, in the position of the coronal margin of the mesial and distal bone of proximal, angular infrabony defects, were investigated. Tracings of the radiographs of 51 mandibular posterior sites, treated by flap curettage, with a mean post-surgical duration of 11.8 years, were measured using a digitizer pad. The group consisting of shallow-side sites (N = 51), exhibited no significant change in the bone height with time; however, there was a significant decrease in bone height in the deep-side group (N = 51). The mean area of proximal bone decreased significantly with time. The defects were divided into early (N = 25) and advanced (N = 26) angular groups, and then into deep- and shallow-side subgroups. In the early defect group, there was a significant decrease in the mean bone height of the deep-side subgroup. There were no differences in the changes of mean bone level of the remaining 3 subgroups with time. There was no correlation between changes in bone levels of adjacent mesial and distal sides of angular defects with time (r = 0.27). There was no difference between the deep- and shallow-side groups in the number of sites which gained, lost or evidenced no change in bone height. In the study population, the bone height of 73% of the deep-side, and 84% of the shallow-side sites was either unchanged or in a more coronal position.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2915052 TI - Clinical parameters and transcutaneous oxygen measurements for the prognosis of venous ulcers. AB - Few data exist on the prognosis of venous ulcers. We therefore prospectively studied 14 patients with severe venous ulcers for up to 18 months and examined various possible prognostic factors, including transcutaneous oxygen tension (TcPO2) measurements of skin next to the ulcers. The ulcers had been present for a mean duration of 15.6 months before referral to our clinic. During the study only four patients (29%) had ulcers that were healed with conservative management consisting of topical and systemic antibiotics and conventional and occlusive dressings. We observed that the number of ulcers, their duration before admission to the study, and the extent of lipodermatosclerosis were more pronounced in the unhealed group. For all patients the mean ulcer TcPO2 level (5.6 +/- 1.5 mm Hg, mean +/- standard error) was significantly reduced when compared with the control chest site (62.4 +/- 2.1 mm Hg) (p less than 0.001; paired t test). The mean ulcer TcPO2 was not significantly different between the healed (4.5 +/- 2.0 mm Hg) and unhealed groups (6.1 +/- 2.0 mm Hg). We conclude that TcPO2 levels may not be predictive of the response to therapy in venous ulcers. TcPO2 levels may be markedly reduced, but even extremely low levels are not incompatible with healing. PMID- 2915053 TI - Ulcerated edematous limbs: effect of edema removal on transcutaneous oxygen measurements. AB - We studied the effect of edema removal on transcutaneous oxygen tension (TcPO2) in eight patients with leg ulcers. An external pneumatic compression device was effective in removing edema from the ulcerated limbs over a 5-day course of treatment, at which time all treated limbs were clinically free of edema. TcPO2 levels at room air at the ulcer site were markedly reduced when compared with the control chest site, both before and after external pneumatic compression device therapy (p less than 0.001). Edema removal, however, did not significantly alter TcPO2 values (p greater than 0.9). No significant positional effects on TcPO2 values were noted with patients supine, sitting, or with the affected limbs elevated. Five patients (63%) had increased TcPO2 values adjacent to the ulcer site when receiving supplemental oxygen. For these patients, TcPO2 values increased after oxygen inhalation, both before and after edema removal (p less than 0.05). We conclude that TcPO2 values are markedly reduced in ulcerated edematous limbs. Edema, however, may not constitute a barrier to oxygen diffusion through the skin and does not account for the low TcPO2 values in the ulcerated edematous limb. Therefore the positive therapeutic effect of removing edema is unlikely to be related to better oxygenation of the tissues. PMID- 2915054 TI - Papulonodular demodicidosis associated with acquired immunodeficiency syndrome. AB - We describe a papulonodular variant of demodicidosis seen in two patients with acquired immunodeficiency syndrome and its successful treatment with 1% gamma benzene hexachloride and 1% permethrin cream rinse. Alterations in T cell function may allow otherwise commensal organisms to proliferate to the point of causing disease. PMID- 2915055 TI - Late circumcision and lichen sclerosus et atrophicus of the penis. AB - We retrieved the records of 20 cases of lichen sclerosus et atrophicus of the penis from pathology service files at five metropolitan hospitals. Histologic sections were available for study in 16 cases. All patient records were available. All cases except one (that of a 14-year-old boy) occurred in men aged 34 to 77 years. Most of the patients (14) were circumcised for phimosis, often with meatal stenosis, and the diagnosis was made on the foreskin specimen. The remaining six patients had already been circumcised, at ages 32 to 54 years, and had lichen sclerosus et atrophicus of the glans penis. Therefore in this series of patients, the condition occurred only in patients circumcised late in life. This must be considered when a decision about neonatal circumcision is made. PMID- 2915056 TI - Actinic lichen planus. A clinicopathologic study of 16 patients. AB - The clinical and histopathologic features of actinic lichen planus in 16 patients were studied. The majority of the patients were young, and men and women were almost equally affected. The relative incidence of this condition, compared with the incidence of all forms of lichen planus, was smaller than that reported in the literature. The eruption was distributed over sun-exposed areas, with particular predilection for the face. Covered areas and mucous membranes were spared except for one patient who had involvement of the vermilion border of the lower lip. In most cases the lesions consisted of erythematous brownish plaques with an annular configuration. Less commonly, discrete and confluent papules and hypermelanotic patches, sometimes assuming a melasma-like appearance, were present. The prominent histopathologic features consisted of an interface dermatitis characterized by coarse vacuolar degeneration of the basal cell layer, a mid-dermal perivascular predominantly lymphocytic inflammatory cell infiltrate, and a significant degree of pigment incontinence. Parakeratosis, eczematous changes confined to the follicular epithelium, and a variable degree of solar elastosis were seen in some patients. Mucin deposition was noted in the reticular dermis in two cases. PMID- 2915057 TI - Granuloma annulare in patients with human immunodeficiency virus infections. AB - We present four cases of granuloma annulare occurring in patients with human immunodeficiency virus (HIV) infection. These patients had either an extensive localized form or generalized granuloma annulare. The patient with generalized granuloma annulare was clinically reminiscent of the previously described papular eruption seen in HIV-positive patients. In several patients with the localized form, Kaposi's sarcoma was considered in the differential diagnosis. In all patients, however, the eruptions were surprisingly transient. The similarity of the localized form of granuloma annulare to Kaposi's sarcoma and the generalized micropapular form to the papular eruption of acquired immunodeficiency syndrome seen in HIV-positive patients illustrates the usefulness of skin biopsies in these patients. PMID- 2915058 TI - Subacute radiation dermatitis: a histologic imitator of acute cutaneous graft versus-host disease. AB - The histopathologic changes of radiation dermatitis have been classified either as early effects (necrotic keratinocytes, fibrin thrombi, and hemorrhage) or as late effects (vacuolar changes at the dermal-epidermal junction, atypical radiation fibroblasts, and fibrosis). Two patients, one exposed to radiation therapeutically and one accidentally, are described. Skin biopsy specimens showed an interface dermatitis characterized by numerous dyskeratotic epidermal cells with lymphocytes in close apposition (satellite cell necrosis); that is, the epidermal changes were similar to those in acute graft-versus-host disease. Because recipients of bone marrow transplants frequently receive total body irradiation as part of their preparatory regimen, the ability of radiation to cause persistent epidermal changes similar to those in acute graft-versus-host disease could complicate the interpretation of posttransplant skin biopsy specimens. PMID- 2915059 TI - Loose anagen hair of childhood: the phenomenon of easily pluckable hair. AB - We report two unrelated boys aged 4 and 9 years who had the recently delineated phenomenon of easily pluckable hair. Hair tufts could be pulled out without effort and without pain. Alopecia without any sign of scalp inflammation or scarring was noted. In the older child spontaneous remission occurred within 3 months, whereas the condition remained active in the younger boy for a follow-up period of 1 year. Trichograms from clinically involved and uninvolved areas disclosed a striking predominance of anagen hairs (98% to 100%) and complete absence of telogen hairs. A loss of the normal round or oval configuration of many hair shafts could be well visualized by the shrinking tube technique. Horizontal and transverse sections of scalp obtained for biopsy revealed marked cleft formations between hair shafts and regressively altered inner root sheaths. We suggest the name loose anagen hair of childhood for this newly described disease. PMID- 2915060 TI - Loose anagen syndrome. AB - A distinctive new hair condition, the loose anagen syndrome, features anagen hairs that are loosely anchored and easily pulled from the scalp. The children studied had sparse hair that did not grow long and that pulled easily from the scalp. The majority of patients were blond girls, aged 2 to 5 years, but both sexes and those with dark hair can be affected. The hair was not fragile, and easily pulled hairs were misshapen anagen hairs without external root sheaths. Histologic examination of the hair showed abnormal premature keratinization of Huxley's and Henle's layers of the inner root sheath in some samples. Length and density of hair gradually increased with age, but anagen hairs remained loosely anchored in adulthood. This report describes findings in 22 children and five adults with the loose anagen syndrome. PMID- 2915061 TI - Effect of oral isotretinoin on dysplastic nevi. AB - We previously reported a favorable histologic response of dysplastic nevi to topical tretinoin in three patients. To investigate the anticancer and cancer preventive effects of retinoids we have examined the effect of systemic isotretinoin on dysplastic nevi. After confirmatory baseline biopsies, eleven patients with the dysplastic nevus syndrome were treated with oral isotretinoin, 40 mg twice a day for 4 months. At completion of therapy, at least three previously identified and photographed clinically typical dysplastic nevi were rephotographed and removed for histologic evaluation. Eight patients completed the full course of medication. There were no clinical changes in the dysplastic nevi in these patients. Posttherapy biopsy specimens in six volunteers revealed most of the remaining lesions to be dysplastic nevi. The majority of lesions biopsied in two subjects showed normal, benign nevi only. This proportion of clinically typical dysplastic nevi that prove to be normal nevi histologically (28%) is not significantly different from that reported by others. Oral isotretinoin does not appear to have a significant biologic effect on the clinical or histologic appearance of dysplastic nevi in the treatment schedule employed. PMID- 2915062 TI - Generalized melanosis in occult primary melanoma. AB - Once encountered, generalized melanosis as a consequence of disseminated melanoma is not easily forgotten. Cases in the literature usually have resulted from primary cutaneous melanoma. A case of generalized melanosis caused by an occult primary melanoma is reported in a patient who originally complained of increased pigmentation. Findings of light microscopic studies of involved skin, pathogenesis of generalized melanosis, and possible sites of origin of the primary neoplasm are discussed. PMID- 2915063 TI - Acquired reactive perforating collagenosis. PMID- 2915064 TI - Lichen planus of the nail: treatment with antimalarials. PMID- 2915065 TI - Eruptive vellus hair cyst and steatocystoma multiplex. PMID- 2915066 TI - Treatment of recalcitrant pyoderma gangrenosum with cyclosporine. PMID- 2915067 TI - Syphilis associated with human immunodeficiency virus infection. PMID- 2915068 TI - Oral sex is not safe sex. PMID- 2915069 TI - Pruritus confined to scapular or subscapular region? Occult Becker's nevus with mild folliculitis. PMID- 2915070 TI - Skin tumors in the European PUVA study. Eight-year follow-up of 1643 patients treated with PUVA for psoriasis. PMID- 2915071 TI - Wells' syndrome. PMID- 2915073 TI - A walk in the woods. PMID- 2915072 TI - Atypical granuloma annulare in patients with the acquired immunodeficiency syndrome. PMID- 2915074 TI - Basal cell carcinoma at the base of the penis in a black patient. AB - Basal cell carcinoma is the most commonly diagnosed malignant skin tumor. It is found most frequently on sun-exposed skin. There is a higher incidence of basal cell carcinoma in white skin than in black skin. We report the thirteenth case of basal cell carcinoma on the penis. To our knowledge, this is the first reported such case in a black patient. PMID- 2915075 TI - Subcutaneous eosinophilic necrosis associated with refractory anemia with an excess of myeloblasts. AB - We followed up over a period of 10 months a Cambodian patient in whom refractory anemia with excess blasts was discovered after the onset of fever and chronic dermatologic involvement. Violaceous, firm, and painful subcutaneous nodules (1-3 cm in diameter) were present on the arms, legs, trunk, scalp, neck, and chin and were associated with violaceous infiltrating plaques on the face and forehead. The microscopic examination of repeated biopsy specimens showed a predominantly lobular panniculitis characterized by an extensive eosinophilic necrosis, leukocytoclasia, and fibrinoid deposits within a few vessels. Such lesions might be the consequence of the immune response against leukemic clones, which have been shown to be present in a steady state in at least some cases involving myelodysplastic syndromes. PMID- 2915076 TI - Treatment of nevus comedonicus with ammonium lactate lotion. AB - A patient with an extensive nevus comedonicus, which is associated frequently with the development of large inflammatory cysts and abscesses within the nevus, responded dramatically within 1 month to a once-daily application of 12% ammonium lactate lotion. A marked beneficial effect on the comedonal component of the nevus was noted. One inflammatory cyst has developed in an area left untreated by the patient, but none have occurred in treated areas since therapy with ammonium lactate lotion was begun. Previous treatments, which were either ineffective or of minimal effectiveness, included oral isotretinoin, topical tretinoin, salicylic acid, lactic acid, and d-tartaric acid creams. PMID- 2915077 TI - Multicentric reticulohistiocytosis in a child with sclerosing lesion of the leg. Immunohistopathologic studies and therapeutic trial with systemic cyclosporine. AB - Multicentric reticulohistiocytosis affecting a 13-year-old boy induced a sclerosing change of the leg. The cellular infiltrate comprising activated T lymphocytes and macrophages and human lymphocyte antigen (HLA)-DR expression by keratinocytes in lesional skin all suggest the involvement of cellular immune reactions. We administered systemic cyclosporine but could not obtain a favorable effect without a concomitant low dosage of prednisone. PMID- 2915078 TI - Abstracts of papers. 18th annual session, American Association for Dental Research. March 15-19, 1989, San Francisco, California. PMID- 2915079 TI - Construct and predictive validities of the Perceptual Ability Test. AB - The construct and predictive validities of the Perceptual Ability Test (PAT) were examined. The results indicate that the PAT is a multidimensional test of spatial abilities, with each of the PAT subtests exhibiting different predictive validity. Furthermore, a linear combination of the PAT subtest scores was found to be more predictive of first-year dental school technique performance than the total PAT score. PMID- 2915080 TI - The student survey of problems in the academic environment in Canadian dental faculties. AB - A survey of problems related to stress encountered by 1,255 Canadian dental students was conducted. Substantial experience with problems was reported infrequently, although most students were affected negatively by at least one problem. Most difficulties concerned students' doubts about harnessing their efforts and abilities to master large amounts of material, which, of necessity, reduced their opportunity to pursue other interests. Few demographic features predicted the level of students' problems, although there was an indication that those who perceived themselves above average academically reported fewer problems. PMID- 2915081 TI - Will oral and maxillofacial surgeons need a medical degree in the future? PMID- 2915082 TI - Performance flaws in root canal therapy by undergraduate students. PMID- 2915083 TI - The advantages of self-study CPR. PMID- 2915084 TI - Advisory committees for dental technology. PMID- 2915085 TI - Curriculum guidelines on ethics and professionalism in dentistry. PMID- 2915086 TI - Dental school curriculum--a 50-year update. PMID- 2915087 TI - Morphology and localization of sunburst varicosities: an electron microscopic and morphometric study. AB - The results of light and electron microscopy of 18 punch biopsies of sunburst varicosities are presented. Sunburst varicosities are widened cutaneous veins located within the superficial vessel net as well as within descending branches, often with an asymmetrically thickened wall. The thickened vessel walls contain collagenous and muscle fibers. Only a few elastic fibers have been detected, as opposed to numerous oxytalan fibers. Electron microscopy reveals an interfibrillar collagenous dysplasia, lattice collagen, and some matrix vesicles. The center of sunburst vessels is found at depths ranging from 175 to 382 microns below the stratum granulosum. PMID- 2915088 TI - Sclerotherapy: review of results and complications in 200 patients. AB - Sclerotherapy is enjoying great popularity as a technique to eliminate unsightly spider and varicose veins. This study of 200 charts reveals a high success rate and a low incidence of long-term adverse sequelae. To minimize complications, several suggestions are made based on clinical observations. As with any procedure, experience, meticulous technique, and good patient rapport are at the heart of its success. PMID- 2915089 TI - Injection sclerotherapy for spider telangiectasias: a 20-year experience with sodium tetradecyl sulfate. AB - A 20-year experience using sodium tetradecyl sulfate (Sotradecol, Elkins-Sinn, Inc., Cherry Hill, NJ) for the injection treatment of spider telangiectasias is reviewed. Of 1426 legs injected, 882 were treated with a 1%-solution injected directly into the spider veins, and 264 were injected directly with a 1/3% solution. With the 1/3%-solution, the remaining 280 legs had the blue veins feeding the spider telangiectasias injected rather than the spider itself. When injected directly into the spider veins, the lesser concentration gave fewer ulcerations and less pigmentation, but equal treatment results. Injecting the subcutaneous feeder veins appears to provide more permanent clearing of the lesions with fewer recurrences and no side effects. No allergic or other major complications occurred with the injection treatments. PMID- 2915090 TI - Applying theory from social psychology and cognitive behavioral psychology to dietary behavior change and assessment. PMID- 2915091 TI - Examination of specific nutrition/health behaviors using a social cognitive model. AB - Nutrition intervention programs are not always successful. In some cases, an insufficient understanding of the interrelationships among factors influencing health behaviors may be responsible for the failures. This study used social cognitive theory, a framework for studying behaviors, to structure the relationships between measurable factors important to the frequency of health oriented food consumption. We developed a model that incorporated factors for social environment, reinforcement, commitment, behavior modeling, knowledge, and attitude relative to the frequency of consumption of four beverages (whole milk, low-fat/skin milk, regular soda, and diet soda). Four-hundred fifty-seven middle aged adults (mean age, 47 years; 58% female) and 709 college students (mean age, 21 years; 50% female) responded to a written questionnaire designed as a self report on frequency of consumption and measures for 10 social cognitive variables. For all four beverages, the model explained 35% or more of the variance in frequency of consumption, thus confirming its predictive power. We used the statistical approach known as path analysis to examine the relationships within the model. The analysis demonstrated that factors influencing the consumption varied between the two age groups (e.g., nutrition knowledge was related to attitude in adult soda-drinking models but not in student soda drinking models) and between forms of the beverages (e.g., for student models, nutrition knowledge was related to taste enjoyment for low-fat/skim milk but not for whole milk).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2915092 TI - Validity of self-estimated and weighed dietary data for assessment of military rations. AB - Validity of food intake values, self-estimated by subjects and weighed by researchers, was evaluated during the assessment of a new military ration. As an addition to food intake measured by the two methods, a third set of intake values was generated by combining food intakes from the self-estimated and weighted data. This combined method is proposed as another reference for assessing validity. The new ration, Meal-Ready-to-Eat (MRE), was the sole source of food for an experimental group of 27 soldiers engaged in a 34-day field exercise. A control group of 30 soldiers ate a freshly prepared (A ration) breakfast and dinner and an MRE lunch. Agreement of mean nutrient intake values from self estimated and weighed data was high among both experimental and control groups (average coefficients of correlation for 16 nutrients, 0.948 and 0.884, respectively). Paired t-tests yielded no significant differences between self estimated and weighed means for nutrient intake but were significantly different from the means obtained by the combined method (p less than .0001). Mean nutrient intakes determined by both the self-estimated and weighed methods approached 90% of the intakes found by the combined method. PMID- 2915093 TI - A simple method for assessing calcium intake in Caucasian women. AB - Calcium intake has been implicated in the etiology of age-related osteoporosis. There is evidence to suggest that many postmenopausal women consume inadequate calcium to maintain calcium balance. One of the most accurate methods of calculating dietary intake is the weighed food record; however, that method is time consuming and unsuitable for large numbers of individuals. To determine the adequacy of calcium intake in the large numbers of postmenopausal women at risk of osteoporosis, simpler methods of assessing calcium intake are required. We therefore developed a food frequency questionnaire and tested it against a 4-day weighed food record in 54 Caucasian women, between 29 and 72 years of age. Twenty six of the women (Group 1) completed a 4-day record and questionnaire within 1 week. Another 28 women (Group 2) completed the questionnaire 1 to 12 months after completing the 4-day food diary. A good correlation (r = .79, p less than .001) was found between the two methods of calculating calcium intake for the 54 women. Independent analysis of Group 1 and Group 2 showed correlation coefficients of 0.81 and 0.78, respectively. The correlation for postmenopausal women (r = .84) was similar to that of premenopausal women (r = .79). The data show that a short, simple questionnaire can be used to rank individuals according to adequacy of calcium intake as a prerequisite to nutrition intervention. PMID- 2915094 TI - Comparison of estimated nutrient intakes by food frequency and dietary records in adults. AB - Sixteen days of dietary recall and records collected over 1 year for 228 respondents were compared with an estimate of "usual" diet based on a 116-item food frequency questionnaire (FFQ) for the study year. Respondents were white and black men and women aged 24 to 51. Mean energy values for the total group were 2,111 kcal for the recall/records and 2,766 kcal for the FFQ, a 31% difference. The mean food energy and nutrient values obtained by the FFQ were consistently and significantly higher than the mean recall/record values for all four race-sex groups, although the degree of difference varied by nutrient, food group, and demographic characteristics of the respondents. For the nutrients compared, the smallest difference between methods was for protein--27% for the total group. The greatest difference was for vitamin A--123% for the total sample. Sex-race specific correlation coefficients between methods were relatively high for calcium, vitamin C, and iron. PMID- 2915095 TI - Calculating the nutrient composition of recipes with computers. AB - The objective of this research project was to compare the nutrient values computed by four commonly used computerized recipe calculation methods. The four methods compared were the yield factor, retention factor, summing, and simplified retention factor methods. Two versions of the summing method were modeled. Four pork entree recipes were selected for analysis: roast pork, pork and noodle casserole, pan-broiled pork chops, and pork chops with vegetables. Assumptions were made about changes expected to occur in the ingredients during preparation and cooking. Models were designed to simulate the algorithms of the calculation methods using a microcomputer spreadsheet software package. Identical results were generated in the yield factor, retention factor, and summing-cooked models for roast pork. The retention factor and summing-cooked models also produced identical results for the recipe for pan-broiled pork chops. The summing-raw model gave the highest value for water in all four recipes and the lowest values for most of the other nutrients. A superior method or methods was not identified. However, on the basis of the capabilities provided with the yield factor and retention factor methods, more serious consideration of these two methods is recommended. PMID- 2915096 TI - Drug-nutrient interaction counseling programs in upper midwestern hospitals: 1986 survey results. AB - A mail survey was conducted to determine the characteristics of drug-nutrient counseling programs provided to hospitalized patients. The survey population included general medical-surgical type hospitals with 175 or more bed capacity in five upper Midwestern states: Illinois, Iowa, Michigan, Minnesota, and Wisconsin. The average return from 289 surveys was 75%. A mean of 64% of responding hospitals provide patient counseling on drug-nutrient interactions. All statistical analysis was by chi-square. Calculations revealed that less than 50% of hospitals require a physician's order to provide drug-nutrient interaction counseling. More than 50% involve a registered dietitian in providing such counseling. The monoamine oxidase inhibitor drugs were cited most frequently as the group of drugs for which counseling was needed. Other drug groups for which patient counseling is needed include: diuretics, anticoagulants, tetracyclines, oral hypoglycemics, insulin, antihypertensives and/or cardiac drugs, antibiotics, and corticosteroids. Having the dietitian or other dietary personnel scan the patient chart was cited most often as the preferred method for detection of patients taking the drugs. A final statistical calculation revealed that there is no difference between teaching and nonteaching hospitals in the number providing a drug-nutrient counseling program. PMID- 2915097 TI - Development and testing of a statistical and graphics-enhanced nutrient analysis program. AB - The authors have developed and tested a nutrient analysis program that will compute and present graphically summary statistics of population and population subgroup nutrient intakes. The program analyzes for 44 nutrients from 5,800 separate food items. Capabilities of the program include: storage of large numbers of diet records and evaluations of their nutrients; calculation of nutrient means and standard deviations; data sorting based on subject characteristics, such as age, sex, and supplement use; and generation of bar graphs and line plots for individual and/or group data. To test this computerized nutrient analysis program, two sets of 3-day diet records from 200 elderly individuals were analyzed. The program was then used to generate means, differences between means, and distribution frequencies of designated nutrients for various population subgroups (e.g., men greater than or equal to 65 years vs. men greater than or equal to 80 years) as well as comparisons with individual files (e.g., Mr. Smith vs. all men greater than or equal to 65 years). The statistical and graphics capabilities also function within the context of recipe analysis and menu planning, which enhances the application of this program in institutional and community nutrition settings. PMID- 2915098 TI - The nutrient intake of a group of older South African hospitalized persons. AB - Data from a dietary survey of patients in a rehabilitation hospital indicated that their nutrient intake was very low in comparison with the RDAs. Those patients are at risk of developing specific nutritional deficiencies. Recommendations to improve the nutrient intake of this group of elderly persons are given. Even if the "perfect diet" were served, however, a patient's food intake might not be sufficient to meet the RDAs because of lack of appetite or because of elevated requirements owing to various illnesses, multiple drug use, and physiological changes associated with aging. In such a patient, the potentially beneficial use of supplements must be considered. PMID- 2915099 TI - Nutrient intakes and iron status in female long-distance runners during training. PMID- 2915100 TI - Formative course evaluation: a positive student and faculty experience. AB - A formative evaluation of a senior-level coordinated undergraduate program course was conducted cooperatively by faculty and students and described by all participants as a worthwhile project. Everyone was given the opportunity to identify problems, strengths, and solutions. Students recognized that their concerns are of interest to the faculty. Students and faculty focused attention on solution identification in a format that promoted productive relationships. Concerns were not viewed as belonging to one individual or to students or faculty, but to the group as a whole. Therefore, recommendations were more likely to be accepted by all. Student participants and faculty agreed that the formative evaluation process was time-efficient and productive and fostered a sense of contribution, commitment, and pride in the continuing development of excellence in the program. The format is easily adaptable to the remaining coordinated courses. The formative evaluation gives evidence of the relative success of past endeavors and provides constructive recommendations for future endeavors. PMID- 2915102 TI - Nutrition information on food labels (ADA timely statement). PMID- 2915101 TI - Development of a rice flour muffin recipe. PMID- 2915103 TI - Marketing of infant formulas (ADA timely statement). PMID- 2915104 TI - President's page: grass roots involvement in nutrition policy. PMID- 2915105 TI - Spectacles for microscopists and astronomers. AB - A special set of spectacles with the lenses reversed (concave anteriorly) were fabricated for use with microscopic and/or telescopic eyepieces in order to reduce the vertex distance and improve the useful field of view. Although these spectacles were found to be of limited use to microscopists, they were essential to the astronomer whose astigmatism could not be corrected with contact lenses. PMID- 2915106 TI - Acanthamoeba dendriform keratitis. AB - A soft contact lens patient complained of persistent redness, blurry vision and photophobia of the right eye. Both tap water and distilled water were used in his contact lens care regimen. Atypical corneal epithelial dendriform patterns were noted and the patient was treated for presumed herpes simplex keratitis and corneal erosion. The definitive diagnosis of Acanthamoeba dendriform keratitis was made upon isolation of the offending organism from the patient's contact lens case. The clinical course is presented to help define early clinical signs of the disease. PMID- 2915107 TI - Effects of nearpoint visual stress on psycholinguistic processing in reading. AB - To date, there have been few studies to evaluate directly the relationship between binocular visual stress and reading performance. This study employed the cloze procedure to demonstrate the effects of nearpoint stress on performance and efficiency in reading comprehension. Using 19 third year optometry students as subjects, binocular stress was simulated by -2.00 D lenses. Performance, as determined by the time to complete the task, was significantly reduced (p less than .03), but no significant differences in accuracy scores were measured. PMID- 2915108 TI - Retinal arterial macroaneurysms. AB - Retinal arterial macroaneurysm is a distinct, infrequently occurring fundus sign usually found in older patients with systemic vascular disease. The lesion arises on a main branch of the retinal artery within the first three orders of bifurcation. Visual disturbance is uncommon, although it may occur as a result of vitreous or retinal hemorrhage or macular edema. This paper presents two cases of retinal arterial macroaneurysm and discusses the diagnosis, etiology, and management of this condition. PMID- 2915109 TI - Carcinoma metastatic to the eye. AB - Cancer is a leading cause of death in America. Cancer to the eye is being diagnosed with increasing frequency. It is now considered the most common intraocular malignancy in adults. Although most ocular metastases do not require treatment, they have important prognostic implications for the patient's overall survival. Diagnostic errors leading to enucleation could be reduced if the incidence of metastatic tumors was always well considered. Presented here are two patients with metastatic tumors and a brief discussion of the nature of this ocular disease. PMID- 2915110 TI - Computerized optometric records and the law. AB - Today, most computerized optometric records contain the financial and business data for a practice. As technology advances in both optometric instrumentation and computerization, data for the optometric examination is also becoming part of the computerized recordkeeping system. This paper discusses legal aspects of computerized optometric examination records with respect to content, patient confidentiality, authentication for litigation defense, and proper handling by staff. PMID- 2915112 TI - Progressive addition lenses. PMID- 2915111 TI - Alternative delivery systems and optometry. PMID- 2915113 TI - Releasing restraints--a nursing dilemma. AB - 1. Although there has been considerable discussion of the use of patient restraints in long-term care settings, the application and removal of restraints remain a major nursing dilemma. 2. External forces, such as hospital administration, legal, family and other societal pressures, and internal constraints such as the nurse's personal values and workload, continue to result in conflict for the staff nurse. 3. A report of a study on the behavioral effects of removing restraints is used as an example of exploring the experience and outcome of restraint removal and the ensuing staff experience of caregiving to the newly unrestrained patient. 4. Nursing actions and environmental conditions must change if patients considered to be problematic or at risk of injury are to be safely freed from restraints. PMID- 2915114 TI - Calming aggressive reactions--a preventive program. AB - 1. Aggressive behavior of nursing home residents towards caregivers, specifically nurse aides, is increasingly a problem in nursing homes. 2. The C.A.R.E. Program was developed to educate nursing personnel about prevention of aggressive incidents through early identification of residents most likely to become abusive. 3. The C.A.R.E. Program utilizes didactic presentation, role playing, sharing experiences, and group support as teaching strategies. 4. A major implication for professional nurses is to assume responsibility for identifying elders at risk for aggression and to provide the nursing team with the training to best care for these residents. PMID- 2915115 TI - A self-care project. The use of landmarks. AB - 1. As caregivers of the gerontological patient, our prime goal is to maintain as much patient independence as possible, thus promoting dignity, self-worth, and cooperation. 2. Knowledge of performance potential for the various stages of Alzheimer's Disease is essential in planning nursing goals which are realistic and useful in resolving self-care deficits. 3. Identification of facility landmarks, orientation checklists, and other visual aids, such as described in this article, are productive nursing interventions in teaching the confused patient to perform basic daily needs. PMID- 2915116 TI - The ISQ-P tool: measuring stress associated with incontinence. AB - 1. ISQ-P is a useful tool in measuring psychological stress associated with urinary incontinence. 2. ISQ-P can be used in conjunction with bladder training programs. 3. Patients with urinary incontinence show depressive symptoms, have somatic concerns regarding urinary incontinence, and exhibit a feeling of shame. PMID- 2915117 TI - Liposomes can function as targets for natural killer cytotoxic factor but not for tumor necrosis factor. AB - NK cells exert their lytic action through the release of NK cytotoxic factors (NKCF) after stimulation by the bound target cell. NKCF may be related to granule derived perforin/cytolysin on one hand and to the pleiotropic cytokine TNF on the other hand. In the present study, we show that NKCF can also lyse artificial lipid vesicles, as had been reported previously for cytotoxic granules and cytolysin. The lysis of large unilamellar vesicles was monitored by measuring the release of the encapsulated fluorescent dye carboxyfluorescein. NKCF-induced lysis was only observed with liposomes composed of a complex mixture of lipids including acidic phospholipids. No lysis could be demonstrated if the liposomes contained phosphatidylcholine as the only phospholipid, suggesting some kind of lipid specificity for the action of NKCF. A remarkable finding was that neither recombinant nor natural TNF were able to lyse large unilamellar vesicles, irrespective of their lipid composition, indicating different ways of interaction of NKCF and TNF with artificial (and presumably also biological) membranes. PMID- 2915118 TI - Inheritance of immune responsiveness, life span, and disease incidence in interline crosses of mice selected for high or low multispecific antibody production. AB - High (H) and low (L) antibody responder lines of mice separated by selective breeding present a maximal interline difference in antibody (Ab) response to Ag of different specificities (general genetic regulation). The analysis of SRBC agglutinin response in H line, L line, F1 hybrids, F2, and backcross segregants demonstrates that Ab responsiveness is a polygenic trait regulated by the additive interaction of 5 to 7 independent loci, with an incomplete dominance (44% +/- 7%) of the high response character, and a 30% +/- 10% impact of the environmental factors. The life span of H, L, F1, F2, and backcross populations is correlated positively with 2-ME-resistant agglutinin response (r = 0.97, p less than 0.001) and negatively with 2-ME-sensitive agglutinin response (r = 0.95, p = 0.01) (interpopulation correlation). Similar correlations are also observed in individuals of the various populations, especially in F1 x L backcross, in which the largest phenotypic variance is found. The positive correlation between Ab responsiveness and life span was confirmed by ELISA titration for distinct IgG isotypes (intrapopulation correlation). Malignant lymphomas and chronic nephritis were the two most common diseases observed. The age-adjusted incidence of such diseases, which is largely affected by environmental factors, accounts for the longer life span of H, as compared with L, mouse populations. The longevity of the 30% or less survivors, chiefly determined by the rate of physiologic aging, is a polygenic character regulated by the cumulative interaction of 3 to 7 independent loci, with a complete dominance of the long life trait and an impact of the environmental factors of about 60%. Thus we have grounds for regarding general Ab responsiveness and life span as polygenic traits regulated by a small number of identical or closely linked gene loci, and immune responsiveness as a defense mechanism against neoplastic and inflammatory diseases. PMID- 2915119 TI - Surface aminopeptidase activity of human lymphocytes. I. Biochemical and biologic properties of intact cells. AB - Surface aminopeptidase activity in intact lymphocytes was studied and was shown to have the following properties when alanine-p-nitroanilide was used as substrate: 1) The activity was surface associated and not secreted as determined by extracellular location of product and the effect of proteases and diazotized sulfanilic acid on enzyme activity. 2) The enzyme activity was shown to have a pH optimum of 7.4 to 8.0. 3) Enzyme activity was shown to be inhibited by amastatin, bestatin, and 1,10 phenanthroline. Inhibition by amastatin consisted of a high affinity component (Ki = 3.5 x 10(-6) M) which accounted for approximately 20% of the total activity and a low-affinity component (Ki = 3.5 x 10(-5) M) which accounted for the remainder suggesting that two forms of aminopeptidase exist. Only a single component of inhibition was seen with bestatin (Ki = 3.5 x 10(-6) M) and 1,10 phenanthroline (Ki = 2.0 x 10(-4) M) which accounted for 80 and 90% of the total enzyme activity, respectively. Unlike the competitive inhibitors bestatin and amastatin, inhibition by 1,10 phenanthroline was shown to be non competitive. Finally, surface aminopeptidase activity essentially doubled in the presence of PHA (10 micrograms/ml) or Con A (10 micrograms/ml), at 72 h. This enhancing effect was shown to be dose dependent, time dependent, and mitogen dependent and correlated with the cellular state of activation as determined by [3H]TdR incorporation. PMID- 2915120 TI - The role of oxidant injury in tumor cell sensitivity to recombinant human tumor necrosis factor in vivo. Implications for mechanisms of action. AB - The intracellular glutathione levels of two human tumor lines and seven murine tumor lines were determined in order to investigate the role of oxidant injury in tumor cell sensitivity to human rTNF (rhTNF). Correlations were found between high intracellular glutathione levels and in vivo tumor resistance to rhTNF, and on the other hand, low glutathione levels and rhTNF sensitivity. The transplantable murine fibrosarcoma, Meth A, a TNF-sensitive line in vivo, was less sensitive to rhTNF and host toxicity was reduced when the hosts were pretreated with uric acid, a major reactive oxygen scavenger in humans and certain other primates. Conversely, pretreatment of the tumor-bearing hosts with DL-buthionine-(S,R)-sulfoximine, an inhibitor of GSH biosynthesis, resulted in an increased sensitivity of Meth A to rhTNF. This effect was not limited to tumor bearing mice, as rats pretreated with diethyl maleate, a compound which irreversibly binds glutathione, were more sensitive to rhTNF toxicity than control rats. On the other hand, pretreatment with N-acetyl cysteine, an oxidant scavenger, reduced the toxicity of rhTNF treatment in rats. The data are consistent with the hypothesis that tumor cell sensitivity to rhTNF in vivo is dependent on its capacity to buffer oxidative attack. In addition, host toxicity is also related to the production of reactive oxygen species. Activated effector cells such as granulocytes and macrophages are hypothesized to produce most of this damage by their respiratory burst and oxidant release, although the direct action of rhTNF may also contribute to oxidative injury in vivo. PMID- 2915121 TI - Immunoreactivity of 111In and 131I fibrin-specific monoclonal antibody used for thrombus imaging. AB - Immunoreactivity of radiolabeled F(ab')2 fragment of anti-fibrin T2G1s monoclonal antibody was determined by affinity chromatography using fibrin-coated Sepharose. This preparation is useful for thrombus detection in vivo by gamma camera imaging, provided a high percentage of immunoreactivity is retained after labeling. For 111In labeling, DTPA/F(ab')2 molar ratios were varied from 1000 to 6600/1, with little effect on immunoreactivity. Immunoreactivity of the F(ab')2 fragment, labeled with imaging doses of 131I and 111In, remained high and ranged from 81% to 89%. Equilibrium binding analysis determined the affinity constants of 111In- or 125I-labeled T2G1s and its F(ab')2 and Fab fragments, to be equivalent (Kd approximately 3 X 10(-8) M). This suggests that only one binding domain of T2G1s binds to fibrin even though there are two antigenic sites/mol of fibrin. PMID- 2915122 TI - Lipopolysaccharide (LPS)-free conditions allow growth and purification of postnatal brain macrophages (microglia) PMID- 2915124 TI - Detection, isolation and characterization of staphylococcal enterotoxin B in protein A preparations purified by immunoglobulin G affinity chromatography. AB - Studies were performed to detect and isolate trace contaminants of staphylococcal enterotoxin B (SEB) in various protein A preparations isolated by affinity chromatography employing human IgG covalently bound to Sepharose 4B. Utilizing an ELISA technique, trace amounts (0.018-0.138%) of SEB could be detected in protein A preparations after separation of the SEB employing a molecular sizing column in a high pressure liquid chromatography (HPLC) system. Trace contamination by SEB could be removed from protein A preparations by an additional DEAE ion exchange chromatography step employing a low ionic strength buffer system (0.005 M NaCl in 0.01 phosphate buffer, pH 7.50). The resulting protein A preparations possessed a purity higher than that observed prior to the final purification step. Polyacrylamide gel electrophoresis (PAGE) analyses of the trace contamination removed from protein A preparations by ion exchange chromatography revealed, in addition to SEB, several additional contaminating polypeptides of an unknown nature. These studies indicate that protein A preparations of high purity can be prepared by employing DEAE ion exchange chromatography in addition to affinity chromatography utilizing immobilized human IgG. PMID- 2915123 TI - The immunocytochemical preservation of IgE and mast cells of the rat. AB - The localisation of IgE to mast cells of rats infested with Nippostrongylus brasiliensis has been studied in an attempt to find a fixation procedure which will best preserve (a) the antigenicity of IgE for immunocytochemical demonstration, and (b) the histochemical staining properties of mast cells. A fixative comprising Carnoy's fluid and picric acid (CPA) best fulfilled these criteria, allowing localisation of IgE to both the plasma membrane and cytoplasm of mucosal mast cells of rat small intestine, but only to the plasma membrane of connective tissue mast cells of rat tongue. Formaldehyde-containing fixatives prevented labelling of IgE in the cytoplasm of mucosal mast cells. PMID- 2915125 TI - The influence of immune complexes, steric effects, and antigen-antigen interactions on the sensitivity of enzyme-linked immunosorbent assays. AB - Serum from mice hyperimmunized with 2,4,6-trinitrophenylated bovine gamma globulin (TNP-BGG) or keyhole limpet hemocyanin have been shown to have enhanced binding to several ligands unrelated to the antigen used for immunization. Addition of the immunizing antigen to the serum can result in increased binding to unrelated ligands and to the polyvinyl chloride surface of microtiter wells in solid-phase enzyme-linked immunosorbent assays. In a competitive binding assay using TNP-BGG-hyperimmune serum adsorbed to the microtiter well followed by an alkaline phosphatase conjugate of BGG in the presence or absence of TNP-BSA, substantial inhibition of BGG binding is seen. Steric hindrance appears to be the major cause of such inhibition since addition of hapten alone has little effect on BGG binding. An antigen-antigen interaction between KLH and TNP is also detectable. Immune complex formation, steric effects, and antigen-antigen interactions potentially have substantial influences on ELISA sensitivity and must be considered as possible sources of artifact in these assays. PMID- 2915126 TI - Direct adsorption of ssDNA to polystyrene for characterization of the DNA/anti DNA interaction, and immunoassay for anti-DNA autoantibody in New Zealand White mice. AB - DNA was adsorbed directly to polystyrene in concentrated NaCl (1.2 M) during simultaneous denaturation to single stranded form by high pH (12.0). Adsorption of single stranded DNA to polystyrene under these conditions (HsDNA) was complete within 15 min. DNA was not dissociated from polystyrene by NaCl concentrations as high as 5.0 M, nor by Tween 20 concentrations up to 50%. The method was ineffective for dT15 adsorption to polystyrene. HsDNA adsorption to polystyrene was compared to an indirect method in which methylated bovine serum albumin (mBSA) was adsorbed to polystyrene after which DNA was electrostatically bound to mBSA. DNA/mBSA interaction was affected by as low as 0.3 M NaCl. Using the DNA/mBSA assay, sera obtained from New Zealand White (NZW) mice showed IgG anti DNA activity in approximately 50% of mice tested. HsDNA assay found greater than 62% of NZW mice have 10 micrograms anti-ssDNA or more per ml serum. Complex formation involving C1q complement and ssDNA in HsDNA assay were shown to be negligible. Anti-DNA autoantibody production by NZW implicated the NZW parental strain in autoimmunity of F1 progeny obtained from the New Zealand Black X NZW cross. PMID- 2915127 TI - Production of monoclonal antibody to human IgG allotype G3M T. AB - An efficient method for the production of monoclonal anti-G3M T antibody is described. IgG3 protein of GM B3ST phenotype was isolated by affinity chromatography on Ricinus communis lectin I-agarose and used for immunization. A mouse hybridoma clone was obtained by fusion of popliteal lymph node cells and P3U1 myeloma cells. The antibody produced was tested for allotype specificity by hemagglutination inhibition and ELISA methods using 101 IgG-allotyping control sera. The antibody was neutralizable by all G3M T-positive sera and entirely nonneutralizable by G3M T-negative sera in the inhibition test, and reacted only with G3M T-positive IgG coats in the ELISA test. The results prove the antibody to be allotype-specific, and therefore practically establishes its monoclonality. PMID- 2915128 TI - Acquired immunodeficiency syndrome and disseminated histoplasmosis. PMID- 2915129 TI - Relapse of rickettsial Mediterranean spotted fever and murine typhus after treatment with chloramphenicol. AB - In the years 1975-1984, 132 patients with rickettsial Mediterranean spotted fever and murine typhus were treated with chloramphenicol or tetracycline. Among the 24 patients who received chloramphenicol ten relapsed and one failed to respond at all. None of the 108 recipients of tetracycline suffered a relapse. It appears that tetracycline should serve as first-line therapy in several rickettsial diseases. PMID- 2915130 TI - Boric acid converts urine into an effective bacteriostatic transport medium. AB - Results of an experiment designed to assess the usefulness of boric acid for preserving urine before its bacteriological examination are reported. Boric acid at a concentration of 20 g/l was found to be usefully bacteriostatic, largely eliminating the false positive results obtained with unpreserved specimens when delay before culture was more than 90 min. The effect lasted for up to 48 h. There was no evidence that borate is toxic to the urinary pathogens encountered in naturally infected urine. Borate also preserves white blood cells in urine and thereby marginally improved the diagnosis of pyuria. The results confirm that boric acid may with benefit be added to bottles used for transporting specimens of urine to the laboratory. PMID- 2915131 TI - Endocarditis due to Streptococcus morbillorum. AB - Two cases of endocarditis due to Streptococcus morbillorum are described. Neither patient had any known history of valvular disease. These are believed to be the first such reported cases in the U.K. In the first case, previous anal surgery and, in the second, drainage of a dental abscess and extraction of a tooth are the likely procedures which initiated endocarditis. The first case is of further interest in that the incriminated strain showed marked tolerance to beta-lactam antibiotics. A combination of penicillin with gentamicin was shown to be required in order to give satisfactory bactericidal activity in vitro. PMID- 2915132 TI - Human immunodeficiency virus infection in the United Kingdom: quarterly report 3. AB - Up to 31 March 1988, 1429 cases meeting the World Health Organization/Centers for Disease Control (U.S.A.) definition of the acquired immune deficiency syndrome (AIDS) were reported in the U.K. of which 59 were in visitors and 1370 in U.K. residents. In the same period there were 8459 laboratory reports of human immunodeficiency virus (HIV) antibody-positive tests. Since 1985 the median interval of 2 months between diagnosis and report of AIDS has not changed. Most patients with Kaposi's sarcoma (KS) as an indicator disease when AIDS was diagnosed were homosexual/bisexual males; the proportion in this category has declined. The data support the hypothesis for a co-factor in the aetiology of KS in homosexual/bisexual males and that the effect of this co-factor has progressively weakened. Injecting drugs was a risk factor for 48 patients with AIDS (4%), half of whom were also homosexual/bisexual males, and for 1406 (17%) persons reported as HIV antibody-positive of whom 63 were also homosexual/bisexual males. HIV-infected persons injecting drugs were reported from all parts of the U.K., apart from Northern Ireland, but the cumulative rate per million population in Scotland for such persons was more than six times the rate elsewhere. In the collaborative laboratory study in England, 2.3% of over 3000 persons injecting drugs were HIV antibody-positive; among those who were asymptomatic the prevalence in London was 7.1% compared with 1.3% outside London. By 1987, the incidence rate of acute hepatitis B in persons injecting drugs in England had fallen to less than a third of that for 1985; in Scotland the figure for 1987 was only a quarter of that for 1985. Since the current rate of HIV transmission among persons in the U.K. injecting drugs is unknown, monitoring the prevalence of HIV in this risk group should be intensified. PMID- 2915133 TI - DF-2 septicaemia following a dog bite in the absence of local inflammation. PMID- 2915134 TI - Staphylococcal scalded skin syndrome. PMID- 2915135 TI - Pulmonary complication in brucellosis. PMID- 2915136 TI - Caution advisable when interpreting gram-stained smears of material from peritoneal paracentesis. PMID- 2915137 TI - Klebsiella meningitis without pleocytosis in the cerebrospinal fluid. PMID- 2915138 TI - Zidovudine. Proceedings of a symposium. London, 27 September 1988. PMID- 2915139 TI - A review of the pharmacokinetics of zidovudine in man. AB - Initial pharmacokinetic and bioavailability data in man were obtained from a phase I, open-label, dose-escalating, multiple-dose study of intravenously and orally administered zidovudine. Dose-independent kinetics were observed over the dose-range 2.0 to 10 mg/kg (oral). Zidovudine is rapidly and extensively absorbed following oral administration. The mean half-life is approximately 1 h. The drug is capable of crossing the blood-brain barrier resulting in antiviral concentrations within the cerebrospinal fluid. The major route of elimination is by hepatic glucuronidation followed by rapid excretion of the metabolite in the urine. Consequently, factors affecting liver or kidney function may alter the pharmacokinetic profile. Although no systematic studies of potential drug interactions have been reported, data are accumulating on the concomitant use of zidovudine with other medications. PMID- 2915140 TI - Zidovudine--the first year of experience. PMID- 2915141 TI - Use of zidovudine for drug misusers infected with human immunodeficiency virus. AB - The use of zidovudine in drug misusers, especially current drug misusers, has not been extensively studied. Since periods of abstinence may be interspersed with drug misuse, it is necessary to establish the safety of zidovudine in injection drug misuse-related human immunodeficiency virus (HIV) infection under a variety of conditions. HIV serology became available in October 1985 and we have now examined medically 289 HIV seropositive patients, 85% of whom acquired their infection via injection drug misuse. Since March 1987 we have treated 40 individuals with zidovudine, 25 of whom were former or current injection drug misusers and one who was a heterosexual contact of a drug misuser. Eighteen patients were taking various types of opiates. Six of this latter group injected either occasionally or regularly whilst taking zidovudine. There were no adverse clinical events associated with zidovudine treatment and continued opiate drug misuse whether by mouth or by injection. Although defaults from clinic visits were a problem, these defaults were not associated with any particular form of drug misuse. Compliance with zidovudine therapy as judged by change in the mean corpuscular volume was no different for the various risk groups. In our experience it is possible to treat safely current and former drug misusers with zidovudine. PMID- 2915142 TI - Zidovudine experience at the Hospitals for Sick Children, Great Ormond Street, London. PMID- 2915143 TI - A scanning electron microscope study of granulocytes of Oncomelania hupensis (Mollusca). PMID- 2915144 TI - Bioassay experiments on the dose response of Mesocyclops sp. copepods to meiospores of Amblyospora dyxenoides produced in Culex annulirostris mosquito larvae. PMID- 2915145 TI - Ingestion, dissolution, and proteolysis of the Bacillus sphaericus toxin by mosquito larvae. AB - Larvae of Culex quinquefasciatus are much more susceptible to the toxin of Bacillus sphaericus than are larvae of Aedes aegypti. In the present study, the rate of ingestion, dissolution, and the cleavage by midgut proteases of the B. sphaericus toxin were compared in larvae of these species to determine whether these factors account for the differences in susceptibility. During filter feeding, larvae of both species removed significant quantities of B. sphaericus toxin from suspensions. Filtration rates for 1 hr, the time at which C. quinquefasciatus exhibited marked intoxication, were higher for A. aegypti (576 713 microliters/larva/hr) than for C. quinquefasciatus (446-544 microliters/larva/hr). Within 24 hr of exposure, A. aegypti larvae ingested 97 99% of the toxin particulates and suffered not more than 10% mortality in suspensions which induced complete mortality in C. quinquefasciatus within 2 hr of exposure. Quantification of the particulate toxin present in larvae after exposure to B. sphaericus suspensions revealed that larvae of both species contained only minor amounts of the toxin, suggesting the larvae had been able to solubilize the toxin after ingestion. Proteases recovered from the feces of larvae cleaved at 43-kDa protein isolated from B. sphaericus toxin extract to 40 kDa in both species. Thus, differences in susceptibility to the B. sphaericus toxin between A. aegypti and C. quinquefasciatus are not due to differences in rates of ingestion, dissolution, or the specificity of proteases. PMID- 2915146 TI - Changes in infectious flacherie virus-specific polypeptides and translatable mRNA in the midgut of the silkworm, Bombyx mori, during larval molt. PMID- 2915147 TI - Leukemia cell specific protein of the bivalve mollusc Mya arenaria. AB - Soft shell clams, Mya arenaria, develop leukemias in the hemolymph which are fatal. Tissue sections and hemolymph samples from normal and tumor-bearing clams were tested with an anti-leukemic cell specific monoclonal antibody (Mab) "IEII." Evaluation of leukemic cells and normal hemocytes by sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blot analyses showed that Mab IEII bound to a large protein of approximately 200 kDa from the tumor cell, but not from the normal cell preparation. PMID- 2915148 TI - Infection of Aedes albopictus by Tolypocladium cylindrosporum. AB - The infection process of Tolypocladium cylindrosporum in Aedes albopictus is discussed. The integument is a common site of infection. Spores of T. cylindrosporum are able to adhere to the exoskeleton and penetrate it. During its early stages of development the fungus is always surrounded by a thick bacterial muff. However these bacteria did not invade the host, and no bacterial cell was observed on the intact cuticle. Conidia filtered by larvae rapidly filled the gut and most of them were hydrolyzed in the midgut. Even if germination occurred at a low level in the digestive tract, the peritrophic membrane and the mesenteral cells were not penetrated by fungus. PMID- 2915149 TI - Environmental factors affecting reproductive incompatibility in flour beetles, genus Tribolium. AB - This paper reports the effect of high temperatures on the reproductive compatibility of geographic strains of flour beetles, Tribolium confusum. Some geographic strains are reproductively incompatible with other strains owing to a maternally inherited microorganism: Males infected with the microorganism are reproductively incompatible with uninfected females. All other crosses are fertile. Previous reports indicated that infected strains can be cured of the microorganisms by culturing the beetles on medium containing tetracycline and that cured males become reproductively compatible. This study reports that raising larvae at high temperatures (37 degrees C) promotes curing. The proportion of individuals cured is a function of sex and the period of exposure to high temperature. PMID- 2915150 TI - Laboratory experiments on infection rates of Amblyospora dyxenoides (Microsporida: Amblyosporidae) in the mosquito Culex annulirostris. AB - Laboratory observations were made of the microsporidian parasite Amblyospora dyxenoides in its natural mosquito host, Culex annulirostris. There were no differences in the numbers of eggs laid and in the proportions which hatched between infected and uninfected females, indicating that the parasite did not affect fecundity. Unlike other species of Amblyospora which have been studied the development of binucleate spores in adult mosquitoes increase with age of the host in both sexes and in females it proceeds independently of egg development and blood feeding. The same trend is apparent for adult mosquitoes which acquired the infection in the larval stage by horizontal transmission from the intermediate copepod host as well as for mosquitoes which acquired oenocytic infections by transovarial transmission. There was considerable variation in the proportion of mosquitoes which became infected after exposure to A. dyxenoides infected copepods. Infections in larval progeny of female mosquitoes infected via spores produced in copepods ranged from 0 to 100% in individual batches and averaged 45.6% with meiospore infections, 19.3% with oenocytic infections, with the remaining 35.7% being uninfected. Similar variability was observed in the progeny of infected female mosquitoes in the second generation after exposure to infected copepods. During experiments in which the microsporidium was maintained in C. annulirostris through 9 successive transovarially transmitted cycles (by selectively rearing the progeny of females infected with binucleate spores after an initial exposure to infected copepods) the proportion of infected progeny with oenocytic infections increased from 25 to around 50% whereas the incidence of meiospore infections declined from 50 to 10%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2915151 TI - Specificity and cross-reactivity of monoclonal antibodies reactive with the core and lipid A regions of bacterial lipopolysaccharide. AB - Twenty-nine murine monoclonal antibodies (MAbs) were prepared against antigenic determinants in the core and lipid A regions of Escherichia coli and Salmonella minnesota lipopolysaccharide (LPS). At least eight distinct MAb specificities were identified. Epitopes recognized by MAbs bearing these specificities were localized in the hexose, heptose, and 2-keto-3-deoxy-D-manno-octulosonic acid regions of the core oligosaccharide and on lipid A. Two groups of MAbs exhibited multispecificity for similar but distinct core- and lipid A-related epitopes. Some core-reactive MAbs cross-reacted with corresponding E. coli and Salmonella rough mutant chemotypes; others were specific for E. coli J5 LPS. Lipid A specific MAbs reacted with free lipid A from diverse sources. Few MAbs reacted with smooth LPS. Antibody cross-reactivity was restricted by inter- and intraspecies differences in covalent core structure and by epitope concealment by overlying O-side chain and core sugars. The putative cross-reactive and antiendotoxic properties of MAbs specific for the core-lipid A complex may be limited by the inability of such MAbs to recognize determinants on "native" LPS. PMID- 2915152 TI - Changes in IgM and IgG antibody concentrations in brucellosis over time: importance for diagnosis and follow-up. AB - Changes in concentrations of IgM and IgG antibodies to Brucella were monitored for at least 13 mo by an enzyme-linked immunosorbent assay (ELISA) in 52 patients with culture-positive brucellosis. Two main patterns were observed. After an initial peak, 29 patients (56%) had a steady drop in their IgG levels, whereas 23 (44%) had more than one peak over time. All patients with a chronic form of brucellosis or a relapse were in the second group. In most cases, Brucella antibodies, although falling to low levels, remained measurable. Cutoff levels for IgM and IgG were calculated after considering serum antibody concentrations in people who had recovered from an infection. A separate normal range was established for occupationally exposed workers. On admission, sera from all patients contained Brucella antibody levels greater than established cutoff levels. Our results show that ELISA is an excellent method for diagnosis and follow-up of brucellosis. PMID- 2915153 TI - Detection of bladder bacteriuria in patients with acute urinary symptoms. AB - Quantitative culture of midstream urine fails to yield a significant microorganism in many patients with acute urinary symptoms. We cultured bladder urine, obtained by aspiration, from symptomatic adults with equivocal findings on standard testing of midstream urine for low numbers of conventional uropathogens and fastidious bacteria. We found 561 (31%) of 1817 women and 36 (12%) of 300 men to be culture positive. Five hundred eighty-one (70%) of 830 isolates were fastidious bacteria; 191 (34%) of 561 culture positive women and 0 of 36 culture positive men had polymicrobic bacteriuria. Bacterial counts were less than 10(5) colony-forming units/mL in 67% of samples; 204 of 406 patients with single species infections had increased leukocyte counts in urine. Patients with symptoms of urinary tract infection who are culture negative on standard testing may harbor fastidious bacteria or low numbers of conventional uropathogens in the bladder. In these patients, culture of bladder aspiration urine for low counts and fastidious species is necessary to diagnose bacteriuria. PMID- 2915154 TI - Piroxicam treatment protects mice from lethal pulmonary challenge with Pseudomonas aeruginosa. AB - The effect of treatment with the nonsteroidal anti-inflammatory agent piroxicam on leukocyte migration to the lungs was investigated after aerosol administration of sublethal doses of Pseudomonas aeruginosa to mice. Piroxicam decreased, in a dose-related fashion, the polymorphonuclear leukocyte recruitment to, and the degree of perivascular and peribronchial infiltration in, the lungs. Piroxicam treatment also protected the animals in a dose-dependent manner from challenge with lethal doses of P. aeruginosa. The effect of piroxicam was not related to direct action of the drug on the microorganisms. Piroxicam treatment maintained the animal's pulmonary defenses against infection while diminishing inflammatory responses against P. aeruginosa, an occurrence decreasing the potential for tissue damage due to phagocytes migrating from circulation. PMID- 2915155 TI - Adult Ixodes dammini on rabbits: development of acute inflammation in the skin and immune responses to salivary gland, midgut, and spirochetal components. AB - Rabbits exposed to female Ixodes dammini (both uninfected and infected with Borrelia burgdorferi) or injected with B. burgdorferi showed an acute inflammatory response in the skin. Granulocytes and monocyte-histiocytes were the predominant infiltrating cells. Spirochetes were detected in the tick feeding cavities in the deep dermis. The inflammatory process was accompanied by polyclonal antibody responses to tick salivary gland components. Western blots showed that immune rabbit serum reacted with proteins of molecular masses of 8, 24, and 36-41 kilodaltons in both unengorged and engorged tick salivary glands. Additional reacting bands in the immunoblot of the engorged salivary gland indicated that new antigenic components of the salivary gland are synthesized during engorgement. Rabbits did not produce antibodies to tick midgut components. Murine monoclonal antibody 11G1 detected outer surface protein A of B. burgdorferi in immunoblots of midguts from unengorged ticks, faintly in engorged salivary gland, and seldomly in unengorged salivary gland, findings suggesting that the spirochete is transmitted to the host via tick saliva during the later stages of feeding. PMID- 2915156 TI - Antibodies to human immunodeficiency virus in the semen of heterosexual men. PMID- 2915157 TI - Kinetics of the humoral immune response measured by antibody-dependent cell mediated cytotoxicity and neutralization assays in genital herpesvirus infections. PMID- 2915158 TI - Recurrences of Clostridium difficile diarrhea not caused by the original infecting organism. PMID- 2915159 TI - HLA antigen contamination of commercial Western blot strips for detecting human immunodeficiency virus. PMID- 2915160 TI - Severe African trypanosomiasis with spurious hypoglycemia. PMID- 2915161 TI - Purulent pericarditis due to Yersinia enterocolitica. PMID- 2915163 TI - Prepublication release of scientific data and the right of the public to know: adapting to our times. AB - Technical innovations for more rapid and cheaper communication have begun to blur the boundaries of professional and other expert fields. This change has greatly widened the market for reliable new medical information, but it has also brought new tensions among authors, journals publishing their papers, and the news media. Does informal publication of new medical information before its appearance in scientific documents injure the interests of authors, journals, and the wider public? The possible answers depend in large part on how physicians should be expected to function in this new age of expanding information and speedier communication. A possible solution for these new problems would be access for all interested parties to journal papers through an on-line system at the point of their acceptance. PMID- 2915162 TI - Aseptic meningitis associated with administration of carbamazepine. PMID- 2915164 TI - Public access to experimental drug therapy: AIDS raises yet another conflict between freedom of the individual and welfare of the individual and public. PMID- 2915165 TI - The case for patient access to experimental therapy. PMID- 2915166 TI - Resistance of influenza A virus to amantadine and rimantadine: results of one decade of surveillance. AB - All clinical isolates of influenza A viruses from patients in Huntington, West Virginia, during the decade 1978-1988 were tested, and 65 of 65 H1N1 and 176 of 181 H3N2 viruses were susceptible to the antiviral action of amantadine and rimantadine. The five resistant viruses were obtained from three members of a family undergoing therapy or prophylaxis with rimantadine. Resistant influenza emerged during treatment with rimantadine and spread to two family contacts, causing typical influenza with fever, myalgia, and cough of 5 days' or less duration. Genetic characterization of the resistant viruses when compared to the susceptible virus isolated on day 1 from the index case revealed a single amino acid change in the transmembrane portion of the M2 protein. In vitro studies showed that rimantadine was significantly more active than amantadine against both H1N1 and H3N2 viruses. Although this resistant influenza was transmitted and caused illness in one family, the absence of naturally occurring resistant viruses suggests that the emergence of new strains of influenza A each few years may prevent the widespread emergence of resistant influenza A virus. PMID- 2915167 TI - Detection of HIV-1 RNA in the lamina propria of patients with AIDS and gastrointestinal disease. AB - Thirty formaldehyde-fixed, paraffin-embedded endoscopic biopsy specimens from the colon and rectum of 25 patients with acquired immunodeficiency syndrome were examined using a [35S]HIV-RNA in situ hybridization procedure. Nine of the specimens contained cells that bound significant amounts of probe. Cells were considered positive if more than 50 grains of silver (over background) per 200 micron 2 were seen over cells that did not stain with eosin. Most of the positive cells resembled macrophages, although cells with condensed nuclei resembling lymphocytes were found. No epithelial cells expressing viral RNA were detected. Formaldehyde-fixed eosinophils gave spurious signals that could be reduced with sulfhydryl modifying agents. HIV-1 may be disseminated in the lamina propria of the gut at low concentrations in some patients but may not be detectable in others. The lower gut lining may be both a portal of initial infection with HIV and a target of disseminated HIV infection. PMID- 2915168 TI - An outbreak of ehrlichiosis in members of an Army Reserve unit exposed to ticks. AB - An outbreak of unexplained illness occurred in members of an army reserve unit after field training in an area of New Jersey endemic for Lyme disease. Nine (12%) of the 74 who attended the exercise had serological evidence of Ehrlichia infection, defined as a single rise in titer of antibody to Ehrlichia canis greater than or equal to 1:160 four weeks after training. Two reservists with early serum samples had documented seroconversion, defined by a four-fold or greater increase in titer of antibody to E. canis, with a peak titer of greater than or equal to 1:160. Reservists with serological evidence of Ehrlichia infection were more than three times as likely to report arthralgia, myalgia, headache, appetite loss, nausea, eye pain, and abdominal pain than the other reservists. No reservist with serological evidence of Ehrlichia infection was hospitalized and most had minimal or no symptoms. This outbreak of ehrlichiosis suggests that the usual symptoms of Ehrlichia infection are milder than previously reported and that ehrlichiosis must be considered in symptomatic persons with recent tick exposure. PMID- 2915169 TI - The epidemiology of AIDS-related Kaposi's sarcoma in San Francisco. PMID- 2915170 TI - Two cases of community-acquired Legionnaires' disease: evidence for association with a cooling tower. PMID- 2915171 TI - Human ehrlichiosis in Oklahoma. PMID- 2915172 TI - Serum IgG antibody to the outer membrane proteins of Campylobacter pylori in children with gastroduodenal disease. PMID- 2915173 TI - Comparative in vitro and in vivo activity of racemic praziquantel and its levorotated isomer on Schistosoma mansoni. PMID- 2915174 TI - The role of the pharmacist in antimicrobial agent therapy. PMID- 2915175 TI - Bacteremia associated with tympanostomy tube insertion. PMID- 2915176 TI - Bacterial endocarditis caused by Streptococcus suis type 2. PMID- 2915177 TI - Chronic travelers' diarrhea in a normal host due to Isospora belli. PMID- 2915178 TI - Tonsillar and pharyngeal tuberculosis in a patient without HIV antibodies. PMID- 2915179 TI - Reticuloendothelial iron stores and hereditary hemochromatosis: a paradox. PMID- 2915180 TI - In vivo distribution and elimination of hemoglobin modified by intramolecular cross-linking with 2-nor-2-formylpyridoxal 5'-phosphate. AB - Modified hemoglobin solutions have potential application as plasma expanders with oxygen-transporting capacity. In a previous study it was found that modification of hemoglobin by intramolecular cross-linking with 2-nor-2-formylpyridoxal 5' phosphate (NFPLP) improves the vascular retention time by a factor of three, and it also improves the oxygen-transporting properties. In the present study we investigated in rats how, after exchange transfusion of a clinically relevant dose, the modified hemoglobin (HbNFPLP) was distributed in the body compared with how the unmodified hemoglobin was distributed. By using a new technetium 99m labeling technique, we found in a scintigraphic study that accumulation of hemoglobin in the kidneys was greatly diminished by the intramolecular cross linking with NFPLP. These findings were confirmed by light-microscopic observations after diaminobenzidine staining. It was concluded that the impairment of kidney function caused by blockade of the tubuli is not to be expected from HbNFPLP. In the liver and spleen, where the free HbNFPLP is possibly eliminated, some accumulation of 99mTc label was observed, but the major part of the extravascular label was diffusely spread throughout the body. This led to the conclusion that important accumulation of undegraded HbNFPLP does not occur in the liver and spleen. Rapid appearance of both hemoglobin and HbNFPLP in the lymph showed that cross-linking with NFPLP does not prevent the distribution of hemoglobin over the interstitial space in the first hours after administration. However, pharmacokinetic analysis demonstrated that transcapillary transfer contributes only to a limited extent to the disappearance from the circulation. During 24-hour infusions of HbNFPLP, a steady state with a constant plasma concentration was easily reached. The latter experiment indicated that the eliminating system does not become saturated during prolonged administration of large doses of HbNFPLP. PMID- 2915182 TI - Preventive effect of malotilate on dimethylnitrosamine-induced liver fibrosis in the rat. AB - Dimethylnitrosamine-induced liver damage, which leads to hepatic failure and death of the animal, was prevented by treatment with malotilate. The accumulation of collagen and the morphologic changes caused by dimethylnitrosamine, such as inflammatory cell accumulation and fibrosis, were also prevented by this drug. Malotilate drastically reduced the increases in the amount of type I procollagen alpha 2-chain mRNA and activities of the enzymes prolyl 4-hydroxylase and galactosylhydroxylysyl glucosyltransferase, which are early events in liver fibrosis preceding the deposition of collagen. Even when started 14 days after dimethylnitrosamine induction, malotilate treatment was able to reduce liver damage. We suggest that the effect of malotilate is a result of the inhibition of inflammation. PMID- 2915181 TI - Fibronectin augments binding of fibrin to macrophages. AB - Because of the demonstrated ability of fibronectin to mediate particle uptake by macrophages and the demonstrated affinity of plasma fibronectin for fibrin, we investigated the ability of plasma fibronectin to augment macrophage binding of fibrin. Fibronectin significantly increased fibrin binding by elicited peritoneal macrophages and isolated hepatic Kupffer cells. The binding of fibrinogen was not augmented in the presence of fibronectin. The small amount of macrophage associated fibrin observed in the absence of fibronectin was primarily internalized, whereas the increment in fibrin binding in the presence of fibronectin remained primarily surface bound, as indicated by susceptibility to removal by trypsin. An amino terminal fibrin-binding fragment of plasma fibronectin could similarly support binding of fibrin by peritoneal macrophages. Greater quantities of fibrin were associated with the macrophages in the presence of protease inhibitors, which inhibited elastase activity, but not in the presence of those that inhibited cathepsin activity, suggesting that an elastase like protease may degrade surface-bound fibrin. Uptake of both fibrin and fibronectin was inhibited by prior treatment of cells with trypsin. Competitive binding studies suggested the presence of a high-affinity fibronectin receptor on peritoneal macrophages. Data from the current study thus support the conclusion that fibronectin augments binding of fibrin to the surface of mononuclear phagocytes. PMID- 2915183 TI - Lung and muscle water after crystalloid and colloid infusion in septic rats: effect on oxygen delivery and metabolism. AB - We compared the effect of crystalloid infusion with that of colloid infusion on extravascular lung water and muscle water in septic rats. We also examined the relationship of lung and muscle edema to arterial oxygenation and muscle energy metabolism during sepsis. Cecal ligation and perforation were used to induce sepsis. Five animals served as sham-operated controls. Five animals were infused with 0.9% saline solution and five with 10% low molecular weight hydroxyethyl starch (hetastarch). Thermodilution cardiac output, plasma colloid osmotic pressure, and arterial blood gases were sequentially measured over a 6-hour interval. At 6 hours, a biopsy specimen was taken from the rectus femoris and the lungs and adductor magnus muscle harvested for gravimetric analysis (wet-dry/dry weight ratio). The colloid osmotic pressure was 16.1 +/- 1.2 mm Hg in the control animals, 9.3 +/- 0.5 mm Hg in the saline solution-infused animals, and 21.6 +/- 0.5 mm Hg in the hetastarch-infused animals at 6 hours (p less than 0.05 saline vs control, hetastarch). The lung wet-dry/dry weight ratio was 3.46 +/- 0.11 in the control animals, 3.74 +/- 0.13 in the saline group, and 3.64 +/- 0.11 in the hetastarch group (difference not significant). Arterial oxygenation was not significantly different in the three groups. Muscle wet-dry/dry weight ratio was 3.11 +/- 0.16 in the control animals, 2.75 +/- 0.12 in the hetastarch-infused animals, and 3.06 +/- 0.08 in the saline-infused group (not significant). There were no significant differences in skeletal muscle energy production or lactate/pyruvate ratio between the three groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2915184 TI - Lung mucociliary transport in asymptomatic asthma: effects of inhaled histamine. AB - Bronchial mucociliary clearance (CB) and tracheal mucus velocity (TMV) were measured during the course of repeated inhalations of histamine in six subjects with asthma who had no symptoms in a double-blind, crossover study with a radioaerosol technique. Subjects inhaled a technetium 99m-labeled ferric oxide aerosol with an aerodynamic diameter of approximately 8 microns. CB was recorded for 2.5 hours with a gamma camera, and TMV measured with a multidetector probe situated over the extrathoracic trachea. Histamine was administered repeatedly in concentrations previously shown to produce a 20% fall in forced expired volume in 1 second and at intervals allowing 90% recovery of pulmonary function. Histamine produced a 28% increase in CB (p less than 0.001, analysis of variance) and an 87% increase in TMV (p less than 0.001, analysis of variance) above control values, which was not significantly different from that previously observed in normal subjects receiving significantly higher concentrations of histamine. We conclude that histamine stimulates the mucus transport mechanism in subjects with asthma and that there is a relative hypersensitivity to histamine when these subjects are compared with normal subjects. PMID- 2915185 TI - Plasma kinetics of complement component C4: comparison of three models. AB - Plasma C4 kinetics were studied in members of a kindred with hereditary incomplete C4 deficiency and in control subjects. Test subjects received iodine 125-labeled C4 intravenously, and plasma disappearance curves for 125I-C4 were plotted. By nonlinear least-squares analysis, we fit two-, three-, and four exponential models of plasma disappearance to the plasma curves of each subject. Goodness of fit was significantly better for all subjects with the three exponential versus the two-exponential model (p less than 0.0005). No further improvement in curve fit was accomplished by using a four-exponential model (p greater than 0.5). Metabolic rates and extravascular/plasma ratios calculated from the two- and three-exponential models were significantly different. As judged by extravascular/plasma ratio, the two-exponential model underestimated the amount of extravascular C4. Furthermore, the two-exponential model significantly over-estimated catabolic and synthetic rates. Hence, our results show that C4 kinetics are not optimally described by a conventional, two exponential model. A possible explanation for our findings is that in previous studies of C4 metabolism, the analysis of plasma radioactivity disappearance curves was done by inspection, whereas we used least-squares analysis, a method that determines the number of exponentials with greater reliability. PMID- 2915187 TI - Abnormal high-density lipoprotein composition in women with insulin-dependent diabetes. AB - To determine whether alterations in lipoprotein phospholipid composition might be an unrecognized factor that contributes to the unexplained acceleration of atherogenesis and the loss of sex-related protection from the development of coronary heart disease in women with insulin-dependent diabetes mellitus, we have estimated levels of neutral lipids, apolipoproteins (A-I, A-II, B), and free cholesterol (FC) in plasma and the four major phospholipid constituents of the very low-density lipoprotein + low-density lipoprotein and high-density lipoprotein (HDL) fractions in 12 ambulatory female patients with varying degrees of diabetic control. Although levels of triglyceride, cholesterol, HDL cholesterol, and lipoprotein phospholipids in whole plasma of the patients with diabetes were similar to those in controls, their FC levels and FC/lecithin ratio, a recently described index of cardiovascular risk, both were abnormally increased (p less than 0.01). In the HDL-containing plasma fraction, concentrations of sphingomyelin, lecithin, and lysolecithin all were significantly reduced (p less than 0.05; p less than 0.01, and p less than 0.02, respectively). These compositional changes may be potentially atherogenic, because a reduction in the phospholipid content of HDL may impair its capacity to promote the efflux of cholesterol from cells, and the transfer of cholesterol ester from HDL to the larger apo-B-containing lipoproteins is inhibited when their content of FC is increased relative to phospholipid. These previously unrecognized qualitative defects, which are inapparent in the routine estimation of plasma lipids, may compromise reverse cholesterol transport and thereby promote atherogenesis in women with insulin-dependent diabetes mellitus. PMID- 2915186 TI - Enzyme-linked immunosorbent assay for human metallothionein: correlation of induction with infection. AB - Very little information is available concerning the relationship between metallothionein and disease in humans. Recently, investigators have used the Cd heme method to measure metallothionein levels in human liver samples obtained from autopsy. This assay, however, is not sensitive enough to measure metallothionein in small tissue biopsy specimens. As an alternative, we report the development of a human metallothionein enzyme-linked immunosorbent assay (ELISA). This assay used high-performance liquid chromatography-purified human metallothionein-1 and purified sheep anti-human metallothionein-1 IgG. A limiting antigen coating concentration of 100 ng/ml and a minimal antibody dilution of 1:4000 were chosen. The sensitivity of the ELISA extended to 300 ng/ml (15 ng). The coefficients of interassay and intraassay variation were 15.4% and 4.2%, respectively. Human livers obtained from autopsy were assayed by this method and the values compared with values obtained by the Cd-heme method. The livers were separated by their autopsy reports into four groups: normal, immunosuppression, cancer, and infection. Livers from the infection group (ELISA 2979 micrograms/gm, Cd-heme 1201 micrograms/gm) contained significantly more metallothionein than those from the normal (ELISA, 1035 micrograms/gm, Cd-heme 245 micrograms/gm) and the immunosuppression (ELISA 1272 micrograms/gm, Cd-heme 221 micrograms/gm) groups (p less than 0.05). The cancer group (ELISA 2415 micrograms/gm) also had significantly elevated liver metallothionein levels. We conclude that this ELISA is sensitive enough for the measurement of tissue samples. Furthermore this assay is comparable to the Cd-heme assay in its ability to reflect metallothionein values among various treatment groups. We postulate that hepatic metallothionein induction is mediated by disease-related mechanisms such as interleukin-1, glucocorticoid secretion, or both. PMID- 2915188 TI - CO production by feces and urine. AB - Virtually all CO production in humans and animals is thought to result from the catabolism of heme, and endogenous CO production (VCO) is used as a measure of heme turnover. Using a rebreathing technique, we found that previously fed mice had an apparent VCO that was 40% greater than that of mice that had been fasted before the study. This unexpected result was shown to reflect an excess CO production by the excreta (feces, urine, or both) of fed mice relative to the excreta of fasted mice. Incubation of feces and urine of humans, rats, and mice demonstrated CO release that was not inhibited by autoclaving or acidification to pH 1. CO release from excreta was markedly reduced, however, under anaerobic conditions, and fed and fasted animals excreted CO at the same rate when their excreta were maintained in an anaerobic state. We conclude that feces and urine can release CO via nonenzymatic, oxidative reactions and, under some circumstances, this source of CO can influence measurements of VCO. PMID- 2915189 TI - The pathogenesis of S. aureus endocarditis. PMID- 2915190 TI - Teaching adolescents with learning disabilities to generate and use task-specific strategies. AB - The effects of an intervention designed to enhance students' roles as control agents for strategic functioning were investigated. The goal was to increase the ability of students labeled learning disabled to generate new strategies or adapt existing task-specific strategies for meeting varying demands of the regular classroom. Measures were taken in three areas: (a) metacognitive knowledge related to generating or adapting strategies, (b) ability to generate problem solving strategies for novel problems, and (c) the effects of the intervention on students' regular classroom grades and teachers' perceptions of the students' self-reliance and work quality. A multiple baseline across subjects design was used. The intervention resulted in dramatic increases in the subjects' verbal expression of metacognitive knowledge and ability to generate task-specific strategies. Students' regular class grades increased; for those students who did not spontaneously generalize use of the strategy to problems encountered in these classes, providing instruction to target specific classes resulted in improved grades. Teacher perceptions of students' self-reliance and work quality did not change, probably because baseline measures were already high in both areas. Implications for instruction and future research are discussed. PMID- 2915191 TI - Social skills deficits as a primary learning disability. AB - Advances in the definition of social skills deficits in children and youth with learning disabilities are presented and critiqued. The proposed modified definition of learning disability by the Interagency Committee on Learning Disabilities, which includes social skills deficits as a specific learning disability, is presented and discussed. This definition is analyzed from primary, secondary, and social learning theory causative hypotheses. Development of an adequate assessment technology is viewed as critical to the identification and classification of social skills deficits in children and youth with learning disabilities. PMID- 2915192 TI - A computer analysis of written language variables and a comparison of compositions written by university students with and without learning disabilities. AB - The utility of computerized analysis of variables cited as predictors of success in written expression was examined. The analysis of compositions written by 423 university students revealed a three-factor structure on 17 variables associated with written expression. A comparison of compositions written by university students with and without learning disabilities was conducted on the three factors identified as vocabulary/fluency, syntactic maturity, and vocabulary/diversity. Students with learning disabilities differed significantly on the factors labeled vocabulary/fluency and syntactic maturity. Students with learning disabilities were not as fluent in word production and in the number of different words used in their compositions as their non-learning-disabled peers. They did, however, produce longer sentences and T-units. The findings of this study suggest that emphasis on the postsecondary level needs to focus on expanding the use of written vocabulary skills, and that the T-unit may not be the best determiner of syntactic complexity at the adult level. PMID- 2915193 TI - Language skills and cognitive processes related to poor reading comprehension performance. AB - Eleven tests were administered to 20 high school readers with learning disabilities (LD) and 20 controls. The objective was to examine the relation between reading comprehension performance and performance on tests of language skills and cognitive processes. As a whole, the performance of the group with LD was significantly below the performance of the controls on all measures. However, the variance on nonverbal tests was greater for the group with LD than for controls; some individuals with learning disabilities performed as well as the controls. Results are discussed in terms of how performance deficits are amenable to remediation by instruction. PMID- 2915194 TI - On Larry B. Silver. PMID- 2915195 TI - More on the "magic cure". PMID- 2915196 TI - Phonological processing, language comprehension, and reading ability. AB - Previous research has indicated a relationship between reading ability and the integrity of certain phonological processing skills--skills that operate on the sound structure of language. This study shows how the deficient phonological processing skills of poor beginning readers can impair their comprehension of spoken phrases and sentences that are disambiguated by prosodic cues (i.e., pitch, stress, and pause). Following a brief summary of the available research literature, two new experiments are reported to illustrate that poor readers do not interpret certain sentences as accurately as good readers do, because they are less able to hold phonological material temporarily in working memory. Further insight into the basis of these differences between good and poor readers is provided by two additional pieces of evidence: The differences between good and poor readers are analogous to those between older and younger children readers, and the performance of poor readers tends to resemble that of younger children reading at their same level (i.e., reading-ability-matched controls). Apparently, good and poor readers tend to differ in the rate at which they develop phonological processing skills. PMID- 2915197 TI - Ethics and resource allocation. PMID- 2915198 TI - Paradigms and family medicine. PMID- 2915199 TI - Prevention of breast cancer. PMID- 2915200 TI - The international classification of primary care--an update. PMID- 2915201 TI - Depression associated with a stroke. PMID- 2915202 TI - Myocardial infarction and denial. AB - Denial, a natural defense mechanism, can be either an appropriate or an inappropriate response to anginal pain. Myocardial infarction sufferers often delay several hours before seeking medical attention, and most deaths from infarction occur before hospitalization. These two facts indicate that denial may contribute to mortality from coronary artery disease. To encourage "stoical" patients to seek medical care, nonthreatening educational approaches to cardiac disease and concentrated efforts to reduce anxiety toward hospitals are needed. Family physicians knowledgeable about the effects of denial can screen cardiac prone patients for inappropriate denial and alter diagnostic approaches in an attempt to lessen the role denial plays in cardiac deaths. PMID- 2915203 TI - Illness visualization and therapeutic adherence. AB - In an attempt to identify a quick, inexpensive intervention for improving adherence to therapeutic plans for acute otitis media, a strategy supported by the health belief model was tested on 141 children and their caretakers. To augment education efforts, caretakers were shown the physical findings of acute otitis media in their child. Results of the intervention test show no effects on follow-up appointment-keeping behavior or on intermediate clinical outcome. The health belief model was not sustained by this test. PMID- 2915205 TI - Is community-oriented primary care a viable concept in actual practice? An affirmative view. PMID- 2915204 TI - Utilization of medical services by single-parent and two-parent families. AB - The purpose of this study was to examine the influence of family structure on the utilization of health care services. Data from the Family Health Utilization Survey, a six-month prospective study, showed that when confounders were controlled using a multiple regression model, being in a single-parent family was predictive of a statistically significant increase in overall utilization of ambulatory health care services. There were no differences between single-parent and two-parent families in rates of hospitalization or emergency room visits. There was a trend toward a higher rate for obtaining telephone advice by the single-parent families and a higher rate of after-hours care among the two-parent families. Single-parent families were also more likely to feel they needed care but did not obtain it. Differences that exist in the health care utilization patterns of single- and two-parent families should be considered in assessing health care needs of families. PMID- 2915206 TI - Is community-oriented primary care a viable concept in actual practice? An opposing view. PMID- 2915207 TI - Herniated lumbar disc associated with pertussis. PMID- 2915208 TI - Nonacute scrotal pain in adolescents. PMID- 2915209 TI - Family medicine as a career choice. PMID- 2915210 TI - Physiological role and selectivity of the in situ potassium channel of the sarcoplasmic reticulum in skinned frog skeletal muscle fibers. AB - The role of K+ as a counterion during Ca2+ release from the sarcoplasmic reticulum (SR) has been investigated. An optical technique using the Ca2+ sensitive dye antipyrylazo III monitored Ca2+ release from skinned (sarcolemma removed) muscle fibers of the frog. Skinned fibers were used since the removal of the sarcolemma allows direct access to the SR membrane. Releases were stimulated by caffeine, which activates Ca2+ release directly by binding to a receptor on the SR. Two different methods were used to decrease the SR K+ conductance so that its effect on Ca2+ release could be assessed: (a) the SR K+ channel blocker, 1,10 bis-quanidino-n-decane (bisG10) was used to eliminate current pathways and (b) substitution of the impermeant ion choline for K+ was used to decrease charge carriers. Both bisG10 and choline substitution caused a concentration-dependent decrease in the Ca2+ release rate. Therefore we conclude that K+ is an important counterion for Ca2+ during its release from the SR. The selectivity of the in situ SR K+ channel to several monovalent cations was determined by substituting them for K+ and comparing their effect on Ca2+ release. The substituted ions were expected to affect Ca2+ release in proportion to their ability to support a counterion flux, which is, in turn, a function of their relative conductance through the SR K+ channel. The selectivity sequence determined by these experiments was K+ = Rb+ = Na+ greater than Cs+ greater than Li+ greater than choline. PMID- 2915212 TI - Intracellular pH-regulating mechanism of the squid axon. Interaction between DNDS and extracellular Na+ and HCO3-. AB - Intracellular pH (pHi) of the squid axon is regulated by a stilbenesensitive transporter that couples the influx of Na+ and HCO3- (or the equivalent) to the efflux of Cl-. According to one model, the extracellular ion pair NaCO3- exchanges for intracellular Cl-. In the present study, the ion-pair model was tested by examining the interaction of the reversible stilbene derivative 4,4' dinitrostilbene-2,2'-disulfonate (DNDS) with extracellular Na+ and HCO3-. Axons (initial pHi approximately 7.4) were internally dialyzed with a pH 6.5 solution containing 400 mM Cl- but no Na+. After pHi, as measured with a glass microelectrode, had fallen to approximately 6.6, dialysis was halted. In the presence of both external Na+ and HCO3- (pHo = 8.0, 22 degrees C), pHi increased due to the pHi-regulating mechanism. At a fixed [Na+]o of 425 mM and [HCO3-]o of 12 mM, DNDS reversibly reduced the equivalent acid-extrusion rate (JH) calculated from the rate of pHi recovery. The best-fit value for maximal inhibition was 104%, and for the [DNDS]o at half-maximal inhibition, 0.3 mM. At a [Na+]o of 425 mM, the [HCO3-]o dependence of JH was examined at 0, 0.1, and 0.25 mM DNDS. Although Jmax was always approximately 20 pmol cm-2 s-1, Km(HCO3-) was 2.6, 5.7, and 12.7 mM, respectively. Thus, DNDS is competitive with HCO3-. At a [HCO3-]o of 12 mM, the [Na+]o dependence of JH was examined at 0 and 0.1 mM DNDS. Although Jmax was approximately 20 pmol cm-2 s-1 in both cases, Km(Na+) was 71 and 179 mM, respectively. At a [HCO3-]o of 48 mM, Jmax was approximately 20 pmol cm-2 s-1 at [DNDS]o levels of 0, 0.1, and 0.25 mM. However, Km(Na+) was 22, 45, and 90 mM, respectively. Thus, DNDS (an anion) is also competitive with Na+. The results are consistent with simple competition between DNDS and NaCO3-, and place severe restrictions on other kinetic models. PMID- 2915211 TI - B-wave of the electroretinogram. A reflection of ON bipolar cell activity. AB - Light-evoked intraretinal field potentials (electroretinogram, ERG) have been measured simultaneously with extracellular potassium fluxes in the amphibian retina. The application of highly selective pharmacologic agents permitted us to functionally isolate various classes of retinal neurons. It was found that: (a) application of APB (2-amino-4-phosphonobutyrate), which has previously been shown to selectively abolish the light responsiveness of ON bipolar cells, causes a concomitant loss of the ERG b-wave and ON potassium flux. (b) Conversely, PDA (cis 2,3-piperidine-dicarboxylic acid) or KYN (kynurenic acid), which have been reported to suppress the light responses of OFF bipolar, horizontal, and third order retinal neurons, causes a loss of the ERG d-wave as well as OFF potassium fluxes. The b-wave and ON potassium fluxes, however, remain undiminished. (c) NMA (N-methyl-DL-aspartate) or GLY (glycine), which have been reported to suppress the responses of third-order neurons, do not diminish the b- or d-waves, nor the potassium fluxes at ON or OFF. This leads to the conclusion that the b-wave of the ERG is a result of the light-evoked depolarization of the ON bipolar neurons. This experimental approach has resulted in two further conclusions: (a) that the d-wave is an expression of OFF bipolar and/or horizontal cell depolarization at the termination of illumination and (b) that light-induced increases in extracellular potassium concentration in both the inner (proximal) and outer (distal) retina are the result of ON bipolar cell depolarization. PMID- 2915213 TI - Male alcoholics' perceptions of their fathers. AB - Male alcoholics who describe their fathers as alcoholic are significantly less likely to perceive themselves as like their fathers when compared with male alcoholics who do not describe their fathers as alcoholic. The findings are discussed in the context of the importance of family history as it relates to treatment interventions with male alcoholics. PMID- 2915214 TI - Some pros and cons of computer-assisted psychotherapy. AB - We briefly describe a method of short-term computer-assisted psychotherapy for stress-related conditions and then reply to a number of objections to the method that have been voiced by professional colleagues. PMID- 2915215 TI - Religious affiliations in mental health research samples as compared with national samples. AB - Religious affiliations of patients in research samples in four major psychiatric journals for the years 1978-1982 were compared with those reported in national samples. Protestants and the unaffiliated were underrepresented, whereas Jewish persons were overrepresented. Catholics used mental health services in proportions similar to their presence in the population at large. These findings suggest that religious affiliation may influence the use of mental health services. PMID- 2915216 TI - Oculocutaneous albinism and schizophrenia-like psychosis. PMID- 2915217 TI - Psychiatric symptoms in dental students. AB - Prior research has suggested that dentistry is a relatively stressful occupation that may place its practitioners at an increased mental health risk. Whether or not this susceptibility to mental distress is also evident in those who are being educated to enter the occupation has not been previously studied. The purpose of the present study was to examine the presence of psychiatric symptomatology in a sample of dental students by using the Hopkins Symptom Checklist. Results indicate that dental students evidenced considerably higher symptom levels than those previously reported in a general population survey. Compared with the general population, dental students showed a mild elevation in somatic symptomatology, a moderate elevation in anxiety and depressive symptomatology, and a marked elevation in obsessive-compulsive symptomatology and interpersonal sensitivity. It is possible that the marked elevations in obsessive-compulsive symptomatology and in interpersonal sensitivity may reflect in part a sensitization to excessive performance demands. This sensitization may manifest itself in cognitive inefficiencies such as indecisiveness, blocking or memory impairment, and excess sensitivity to the evaluative judgments of other people. In comparing dental students with other sample groups, dental students were also found to evidence more psychiatric symptomatology than general medical patients judged free of psychiatric illness, and to approach levels of symptomatology found in general medical patients judged psychiatrically ill or in need of psychiatric treatment. PMID- 2915218 TI - Medical student distress. A longitudinal study. AB - This longitudinal study investigated the relative importance of correlates of psychological distress in first year medical students (N = 312) in September and May. Anxiety levels were one SD above the mean when compared with nonpatient levels in both September and May, and the percentage of students reporting depression doubled over the study period. Problem-focused coping decreased, emotion-focused coping increased, and satisfaction with social supports decreased over the year. In contrast, type A behavior and anger expression were more stable. Students distressed in September were at higher risk for distress in May. Students distressed in May were also characterized by higher scores for suppressed anger and type A behavior in May, even after controlling for distress in September. PMID- 2915219 TI - A qualitative review of psychosocial treatments for bulimia. AB - This review covers 32 individual and group therapy studies of the psychosocial treatment of bulimia published between 1976 and 1986. Using 14 criteria to assess the quality of experimental methodology, three studies were rated as high, 17 as medium, and 12 as low. Common methodological problems included the failure to use a control group or to specify the experience level of the therapist, overreliance on self-report outcome measures, and small sample sizes. Great variability was found among studies in inclusion criteria, treatment length, and length of follow up. Thirty-eight percent of patients in group therapy and 41.5% of those in individual therapy were totally abstinent from bingeing and purging at follow-up. Although most studies used behavioral or cognitive-behavioral strategies, no modality of treatment has shown clear superiority. The results are discussed in terms of their implications for treatment, training, and future research. PMID- 2915220 TI - Childhood stress disorder behaviors in veterans who do and do not develop posttraumatic stress disorder. AB - The purpose of this study was to test a variation of the stress-evaporation theory, which maintains that posttraumatic stress disorder (PTSD) symptoms are simply exacerbations of behaviors present before the trauma. Retrospective childhood self-ratings were made by 63 PTSD patients, 53 psychiatric controls, and 28 normals on 13 PTSD-like symptoms. The results did not support the hypothesis, and they give more support to the residual-stress model than to the stress-evaporation theory. PMID- 2915221 TI - Familiality of DSM-III dramatic and anxious personality clusters. AB - This double-blind family study was an investigation of the familiality of DSM-III avoidant, dependent, borderline, anxious cluster, and flamboyant cluster personality disorders (PDs) using a standardized DSM-III axis II measure. With the exception of borderline personality, there are no previous reports in this area. Avoidant, dependent, and anxious cluster PDs showed significant familiality. Borderline showed a trend in the direction of familiality but did not reach significance (p = .07). Relatives of flamboyant cluster PDs demonstrated significant but heterogeneous personality disorder pathology. PMID- 2915222 TI - Barbiturate effects on EEG abnormality in complex partial epilepsy. AB - Sixteen patients with drug-resistant complex partial epilepsy were, during preoperative investigations for surgical treatment, subjected to intravenous methohexital and amobarbital EEG activation tests. The interictal epileptic spike discharges were visually counted on the seizure-generating side and compared with those found in the contralateral hemisphere. The invasive recordings were made with depth electrodes implanted in the mesial temporal lobes of 5 patients, and with subdural strip electrodes in varying lateral positions over the frontotemporal-parietal lobes of the other 11 patients. The doses of 10% amobarbital, 50-200 mg, were too low to induce any significant activation. In eight patients with unilateral epileptic lesions, 10, 25 and 50 mg 1% methohexital, induced a dose-dependent increase in the interictal spiking, always higher on the side of the seizure-gererating focus. Asymmetric induction of beta activity was noted in five patients. The test gave valuable information when determining the type or location of the epileptic abnormality. Parallels were drawn with earlier studies on spike-activation tests after intracarotid amobarbital injections. Although administered differently, the barbiturates are supposed to act directly on the neurons, and not via integrative wakening mechanisms. PMID- 2915223 TI - Demonstration of zoster virus antibodies in cerebrospinal fluid cells. AB - A method is presented that allows the immunocytochemical detection of varicella zoster virus antigen-binding cerebrospinal fluid cells in zoster ganglionitis. Antigen-binding cells were found only in patients suffering from this disease. The technique is sensitive, specific, inexpensive and relatively fast, and is potentially applicable to other inflammatory central nervous system diseases with immunoglobulin-containing cells (ICC) in CSF. The detection of antigen-binding CSF cells may represent a very early diagnostic test comparable with the early IgM antibodies of the systemic immune response. PMID- 2915224 TI - Cryptococcosis in AIDS patients: observations concerning CNS involvement. AB - The clinical course and response to therapy of seven patients with cryptococcosis and AIDS were reviewed. One patient was still in the primary stage of cryptococcosis in AIDS, i.e. the stage that is characterized by the sole cultural detection of Cryptococcus neoformans in the respiratory tract. The other six patients were in the secondary stage, where C. neoformans can be detected from the cerebrospinal fluid (CSF), blood, urine, faeces and other body sites. The main presenting features (headache, fever, nausea) were due to central nervous system involvement, although meningism and mental changes were rarely present, and CSF changes were very subtle. Treatment with amphotericin B and flucytosine was very effective, there being no more growth of fungi in cultures in most cases. Adverse reactions to the drugs used occurred frequently and consisted mainly of anaemia, hepatosis and fever. Diagnosis in the primary stage of cryptococcosis may improve the prognosis. PMID- 2915225 TI - Correlation between multimodal evoked potentials and magnetic resonance imaging in multiple sclerosis. AB - Sixty multiple sclerosis (MS) patients (33 definite, 13 probale and 14 suspected were investigated by computed tomography (CT), magnetic resonance imaging (MRI), multimodality evoked potentials (EPs) and cerebrospinal fluid (CSF) electrophoresis. MRI abnormalities were found in 50 cases, while at least one abnormal evoked potential was detected in each of 52 cases. Brain-stem auditory evoked potentials were more sensitive than MRI for the detection of brain-stem involvement. All the patients with oligoclonal bands had abnormal MRI and none of the patients with normal MRI had oligoclonal bands in the CSF. The number and the extent of MRI lesions were significantly correlated with the duration of disease and with the degree of disability. Our observations stress the importance of the combined use of MRI and EPs in detecting silent CNS lesions in MS patients. PMID- 2915226 TI - Muscle hypertrophy in Duchenne muscular dystrophy. A pathological and morphometric study. AB - In order to investigate the pathological basis of muscle hypertrophy in Duchenne dystrophy, 9 biopsy specimens of the lateral gastrocnemius and 7 of the vastus lateralis were compared. All patients had calf hypertrophy and normal strength in gastrocnemius-soleus, whereas the quadriceps biopsied were all atrophied and weak. The patients' ages ranged from 4 to 11 years. The pathological and histochemical changes were assessed semi-quantitatively. Comparison of the gastrocnemius and quadriceps groups showed that the number of hypercontracted fibres, the degree of endomysial fibrosis and the degree of fat infiltration were significantly higher in the quadriceps. The fibre type differentiation was better in the gastrocnemius group. The mean fibre diameter was above normal in all gastrocnemius biopsies and showed no increase with age. In the quadriceps, fibre hypertrophy was found early in the disease but had changed into fibre atrophy in the three oldest patients. When present, fibre hypertrophy involved both fibre types. The amount of fat-fibrosis per unit area was increased in both groups, but more severely so in the quadriceps. These results indicate that there is no true muscle hypertrophy in the gastrocnemius, in which the fat-fibrosis component was increased in all patients and that the dystrophic process is more active in the quadriceps. The finding of persistent fibre hypertrophy in the gastrocnemius is discussed with respect to the postural abnormalities observed in the lower limbs in Duchenne dystrophy. PMID- 2915227 TI - Clinical correlation of CT changes in 64 Chinese patients with tuberculous meningitis. AB - CT changes in 64 Chinese patients with proven tuberculous meningitis were compared with the clinical features at diagnosis. In patients presenting with advanced disease, hydrocephalus and cerebral infarction were common, and the hydrocephalus in these patients was more likely to require surgery at a later date for control of raised intracranial pressure. New infarctions were only seen in follow-up scans of patients who had presented with disturbed consciousness. Meningeal enhancement, the commonest finding, and intracranial tuberculomata were not related to the severity of disease at presentation. A normal scan in a drowsy patient virtually excludes the diagnosis of tuberculous meningitis. PMID- 2915228 TI - Familial myopathy with scapulohumeral distribution, rigid spine, cardiopathy and mitochondrial abnormality. AB - A 37-year-old woman with scapulohumeral muscular atrophy, rigid spine and cardiopathy is reported. Muscle weakness, advanced atrioventricular block and contractures at the neck, elbows and ankles had occurred during her childhood. An autosomal dominant mode of inheritance was suggested because her mother, sister and brother had the same disorder. Pleomorphic mitochondria had accumulated in the subsarcolemmal space of the skeletal muscle. There was no evident enzyme defect in the mitochondrial electron transport system. Although the clinical features had some similarity with those of Emery-Dreifuss muscular dystrophy or rigid spine syndrome, the pattern of inheritance and the muscle pathology differed. PMID- 2915229 TI - Kluver-Bucy syndrome in systemic lupus erythematosus. AB - The Kluver-Bucy syndrome has not been previously reported as a complication of systemic lupus erythematosus (SLE). A 48-year-old female is described who sustained several cerebral infarcts, some of which were bitemporal, due to SLE vasculopathy. She developed a complex behavioural picture consisting of global aphasia, left-side neglect, hyperorality, hypermetamorphosis and hypersexuality. She displayed appropriate emotional reaction to visually presented objects, indicating that her Kluver-Bucy syndrome could not be explained by lack of visual recognition. PMID- 2915230 TI - T4, T3 and rT3 levels in serum and cerebrospinal fluid of patients with amyotrophic lateral sclerosis. AB - Thyronine (T4), triiodothyronine (T3), and reverse-triiodothyronine (rT3) levels were evaluated in cerebrospinal fluid (CSF) and in serum of 12 patients with definite amyotrophic lateral sclerosis (ALS) by specific radioimmunoassays. Circulating microsomal and thyroglobulin antibodies were also evaluated. In all patients serum levels of T4, T3 and rT3 were within normal limits. In CSF, the rT3 levels were significantly elevated to 0.118 micrograms/l (mean), the T4 levels were not significantly elevated, and the T3 levels were below the detection limit of 0.03 micrograms/l. A correlation between the elevated rT3 levels in CSF and the severity or type of ALS could not be demonstrated by this study. The antithyroid antibodies (thyroglobulin antibodies, microsomal antibodies) showed normal titres and did not suggest disturbances of thyroid autoimmunity in the patients with ALS. PMID- 2915231 TI - Limbic system symptomatology associated with colloid cyst of the third ventricle. AB - The clinical manifestations of olfactory and gustatory hallucinations are commonly attributed to temporal lobe involvement. The case is presented of a 46 year-old man with prolonged episodes of olfactory and gustatory hallucinations, who was found to have a colloid cyst of the third ventricle. Exhaustive electroencephalographic and radiological studies were negative except for the cyst. Stereotaxic aspiration of the cyst resulted in immediate cessation of all symptomatology with a follow-up of 14 months. PMID- 2915232 TI - Relapse of multiple sclerosis following acute allergic reactions to plasma during plasmapheresis. AB - In a small pilot study of plasmapheresis in chronic progressive multiple sclerosis, two patients suffered relapses following an acute allergic reaction to plasma. It is suggested that allergic reactions may have played a role in the exacerbation and recommended that fresh frozen plasma be avoided in therapeutic trials for multiple sclerosis. PMID- 2915233 TI - Analgesic-induced chronic headache: long-term results of withdrawal therapy. AB - Headache characteristics are described in 139 patients with chronic daily or almost daily headaches due to regular intake of analgesics and the short- and long-term results of drug withdrawal. Drug-induced headache was described as dull, diffuse, and band-like, and usually started in the early morning. The mean duration of the original headache (migraine or tension headache) was 25 years; regular intake of drugs and chronic daily headache had started 10 and 6 years prior to withdrawal therapy, respectively. Patients took an average of 34.6 tablets or analgesic suppositories or antimigraine drugs per week containing 5.8 different substances. The drugs most often used were caffeine (95%), ergotalkaloids (89%), barbiturates (64%), and spasmolytics, paracetamol, and pyrazolone derivates (45%-46%). A total of 103 patients (68 migraine, 35 tension or combination headache) were available for interviews at a mean time interval of 2.9 years after an inpatient drug withdrawal programme. Chronic headache had disappeared or was reduced by more than 50% in two-thirds of the patients. Positive predictors for successful treatment were migraine as primary headache, chronic headache lasting less than 10 years, and regular intake of ergotamine. Drug intake was significantly reduced and patients used single substances more often. Patients who originally suffered from migraine, superimposed on the daily headache, also experienced a significant improvement in the frequency of the migraines and their intensity. Migraine prophylaxis through beta-blocking agents and calcium channel antagonists was more efficient after drug-withdrawal therapy. PMID- 2915234 TI - Non-Hodgkin's lymphomas of childhood: an analysis of the histology, staging, and response to treatment of 338 cases at a single institution. AB - Between 1962 and 1986, a total of 338 consecutive newly diagnosed children and adolescents with non-Hodgkin's lymphomas (NHLs) were evaluated and treated at St Jude Children's Research Hospital (SJCRH). Median follow-up is 6.6 years (range, 1.8 to 23 years). The patients ranged in age from 7 months to 21 years (median, 10 years), and 71% were males. All cases were staged (I to IV) by a clinical staging system. Eighteen percent were stage I, 21% stage II, 43% stage III, and 18% stage IV. Cases frankly leukemic at diagnosis (ie, greater than 25% marrow blasts) were excluded from the analysis. Pathologic material from all cases was reviewed and classified according to the Working Formulation. The histologic distribution of cases was as follows: 38.8% diffuse small non-cleaved cell (undifferentiated, Burkitt's and non-Burkitt's); 26.3% diffuse large-cell, mainly immunoblastic; 28.1% lymphoblastic; and 6.8% other. Treatment policy evolved over time to a stage- and histology-specific strategy for treatment assignment, and overall results significantly improved by era from 37% (+/- 5%) 2-year event-free survival (EFS) for patients treated before 1975 to 77% (+/- 4%) since 1978. By univariate and multivariate Cox regression analyses, the era of treatment (hence, the protocol-specific treatment itself), the stage, and the log of the initial serum lactic dehydrogenase (LDH) emerged as the most powerful prognostic indicators, while histology per se was not significantly related to outcome. For the 154 patients treated since 1978, the 2-year EFS by stage was 97% (+/- 3%) for stage I, 86% (+/- 6%) for stage II, 73% (+/- 6%) for stage III, and 47% (+/- 11%) for stage IV (P less than .0001). Compared with our previous experience, we conclude that the cure rate of childhood NHL has doubled in the last decade with modern management. PMID- 2915235 TI - Results of intensive therapy in children with localized alveolar extremity rhabdomyosarcoma: a report from the Intergroup Rhabdomyosarcoma Study. AB - Preliminary analyses of treatment results and prognostic factors from the first Intergroup Rhabdomyosarcoma Study (IRS I) suggested that alveolar histology and extremity site were among factors associated with an adverse outcome in clinical group I patients whose tumors had been completely resected. A high incidence of alveolar histology among the extremity tumors compounded the problem. These findings prompted an amendment to IRS II shortly after the study opened. Therapy for patients with alveolar extremity tumors in groups I and II was changed to more intensive repetitive pulse vincristine, dactinomycin, and cyclophosphamide (VAC) for 2 years. The outcome of 44 patients who received intensive therapy on IRS II is compared with a control series of 30 patients who were treated on IRS I. The control patients received standard VAC therapy for 2 years or VA for 1 year. Half of group I control patients received local radiotherapy, whereas none was given to group I intensive therapy patients. In both studies group II patients received radiotherapy to the primary tumor site and to identified positive regional lymph nodes. Compared with the control group, patients given more intensive therapy had a longer disease-free survival (DFS) (69% v 43% at 3 years), but this was of marginal significance (P = .06). The overall survival difference (77% v 57% at 3 years) was not significant (P = .23). Despite the limited statistical evidence, there is some indication that intensive therapy improved the prognosis of children with localized alveolar rhabdomyosarcoma (RMS). PMID- 2915236 TI - Therapy for localized Ewing's sarcoma of bone. AB - Fifty-two previously untreated patients with localized Ewing's sarcoma of bone were treated with nonintensive chemotherapy in combination with surgery or radiation therapy (RT). RT was delivered to limited volumes in a dose dependent on the initial response to induction chemotherapy (30 to 35 Gy v 50 to 55 Gy). Fifty of the 52 patients achieved complete or partial responses with induction chemotherapy, with one nonresponding patient rendered free of tumor with surgery. Fifty patients were evaluable for local control of tumor and overall response to protocol therapy. Seventeen relapses have occurred; three metastatic, four local plus metastatic, and ten local. Two factors predicted worse disease-free survival: high WBC count (P = .03) and size of primary tumor (P = .05). Of the 14 local recurrences, 12 occurred in 28 patients who presented with primary tumors greater than 8 cm in size while only two of 22 patients with lesions less than 8 cm had local recurrence. The Kaplan-Meier estimate of disease-free survival at 3 years is 82% for those with small lesions and 64% for those with larger lesions. Site of primary was of no prognostic value (P = .27). The 5-year survival estimate for all patients is 80% (median time on study, 3.3 years). PMID- 2915237 TI - A prospective study of Hickman/Broviac catheters and implantable ports in pediatric oncology patients. AB - We prospectively studied the continuous function and complication rates of 286 central venous catheters consecutively placed in 264 children and young adults at a single institution over a 19-month period (median follow-up, 376 days). Externalized catheters (91 Hickman [H], 113 Broviac [B]) and implantable ports (n = 82) were compared for complications, including infection and thrombosis. The most frequent major complication of all catheters was infection, although the rates of infection varied with the duration of catheter use and were generally lower than reported by others. Overall, when catheter failures (removal) for infection, obstruction, or dislodgement were considered, ports had a significantly longer failure-free duration of use (P = .0024) than did externalized catheters. Likewise, ports had a significantly longer infection-free (P less than .01) duration of use than H and B catheters. However, differences in patient age and clinical characteristics among the three catheter groups may have affected the outcome. In analysis of pairs matched for diagnosis, therapy, and age, ports had lower infection rates than did B catheters after 100 days (P = .053). This difference became significant at 400 days of catheter use (P = .029). Although there was a trend toward lower rates of infections for ports v H catheters, this difference was not significant. In view of our results in matched pairs, selection of catheter type based on clinical characteristics and patient preferences remains a reasonable therapeutic approach despite the apparent advantages of ports. The superiority of ports for long-term use (greater than 100 days) needs to be confirmed in a large randomized clinical trial. PMID- 2915238 TI - Ten-year follow-up of patients receiving cisplatin, doxorubicin, and cyclophosphamide chemotherapy for advanced epithelial ovarian carcinoma. AB - Fifty-six patients were randomly assigned to receive either one-day cisplatin, doxorubicin, and cyclophosphamide (PAC) chemotherapy (PAC-I) or five-day PAC (PAC V) for advanced epithelial ovarian carcinoma. Follow-up has been 120+ months or to death. Ninety-one percent had either suboptimal stage III or stage IV disease and 55% had grade 2 or 3 lesions. Two patients died of toxicity and were free of disease at autopsy. A third patient died of congestive heart failure with no disease at 103 months. Additionally, eight patients had a negative second-look laparotomy, and three (37.5%) are alive with no evidence of disease (NED) 133 to 144 months after diagnosis. Five patients (62.5%) died of disease 2 to 123 months after negative second-look. Patients with optimal stage III disease had a longer median progression-free interval (PFI) and survival (33.3 and 44.5 months, respectively) than those with suboptimal or stage IV disease (16.4 and 22.5 months, respectively), and the difference in median PFI is significant (P less than .02). Patients with ascites at diagnosis had a shorter median PFI and survival (14.7 and 18 months) than those without ascites (30.0 and 33.0 months). Both differences were significant (PFI, P less than .04; survival, P = .005). PAC produces response rates that are superior to those obtained historically with single-agent alkylating therapy. Late recurrences after negative second-look laparotomy suggest that 5-year survival data may be inadequate in ovarian carcinoma. PMID- 2915239 TI - Intraarterial cisplatin and concurrent radiation for locally advanced bladder cancer. AB - Between 1983 and 1987 25 patients with invasive bladder cancer (16 stage tumor 3 (T3) and nine stage T4) were treated with intraarterial cisplatin and concurrent radical radiation (20/25) or intraarterial cisplatin, concurrent preoperative radiation, and cystectomy (5/25). One patient died from treatment-related toxicity. Other toxicities have been what one would expect from the individual treatment modalities except for a sensory sacral root neuropathy in 11 of 24 (46%) patients. Twenty-three of 24 (96%) patients achieved a complete response (CR) and the projected actuarial 2-year survival is 90%. Only one of the 23 complete responders has had an invasive local recurrence. The excellent complete local response and survival rates achieved warrant further study of the combination of intraarterial cisplatin and radiation as a bladder-preserving strategy. PMID- 2915240 TI - Excellent outcome of stage II neuroblastoma is independent of residual disease and radiation therapy. AB - The optimal management for patients with stage II neuroblastoma has not yet been established. In order to determine the impact of adding chemotherapy and/or radiation therapy to surgery, we reviewed by questionnaire 156 patients with stage II neuroblastoma treated by 28 Childrens Cancer Study Group (CCSG) institutions from 1978 to 1985. Survival and progression-free survival (PFS) were analyzed by life-table methods with respect to age at diagnosis, site and size of primary tumor, spinal cord involvement, extent of initial resection, and treatment in addition to surgery. The overall 5-year survival was 96%; the PFS was 90%, similar to previous CCSG studies. Age at diagnosis had a small impact on PFS, with 92% PFS for patients less than 2 years of age at diagnosis, and 84% for those greater than 2 (P = .10). The only site with an adverse outcome was the head and neck (n = 11), with a PFS of 68% compared with 93% for the remaining sites (P = .02). Size of primary and intraspinal extension of primary did not affect PFS. The extent of resection and subsequent treatment with radiation therapy and/or chemotherapy did not affect the PFS. The outcome for 75 patients treated with surgery alone (6-year PFS, 89%) was not significantly different from that of 66 patients receiving radiation therapy (6-year PFS, 94%). There was no significant difference between 40 patients with gross or microscopic residual disease treated with surgery alone (PFS, 92%) and 59 patients with residual disease who also received radiation (PFS, 90%). Five of seven patients who progressed after surgery alone have been salvaged with further therapy and are now free of disease. One survives with disease, so that the 6-year survival is 98% for those treated initially with surgery alone, compared with 95% for those receiving radiation therapy and/or chemotherapy. These data suggest that surgery alone, even if complete resection is not achieved, is sufficient initial therapy for stage II neuroblastoma. The data also identify another stage of neuroblastoma, in addition to stage IV-S, for which almost all patients have a favorable prognosis because their tumor may be biologically limited in growth. PMID- 2915241 TI - Selective intraperitoneal biochemical modulation of methotrexate by dipyridamole. AB - Dipyridamole increases the toxicity of methotrexate in a concentration-dependent manner. We hypothesized that concurrent intraperitoneal administration of both drugs would result in high peritoneal concentrations with much lower plasma concentrations, permitting a selective increase in the activity of methotrexate against intraperitoneal tumors without enhancing systemic toxicity. Initially, 2.16 mg/m2/d methotrexate and 12 mg/m2/d dipyridamole were delivered together as a constant intraperitoneal infusion for 48 hours. With escalation of chemotherapy, eventually 4.32 mg/m2/d methotrexate was administered for 168 hours. Forty-seven courses were administered to 18 patients. The mean peritoneal to plasma concentration ratios of methotrexate and non-protein bound dipyridamole were 71.6 +/- 34.8 and over 2,300, respectively. Chemical peritonitis was the dose-limiting toxicity. Three patients had some evidence of a response (two with decreasing tumor markers, and the third with a reduction in ascites). We conclude that the drug concentrations are in an appropriate range for selective intraperitoneal biochemical modulation of methotrexate, and that it is feasible to expose tumors confined to the peritoneal cavity to these drugs for long periods of time. PMID- 2915242 TI - Abdominal lymphoma and intestinal perforation. PMID- 2915243 TI - Reversible acute and subacute myelopathy in patients with dural arteriovenous fistulas. Foix-Alajouanine syndrome reconsidered. AB - Acute or subacute neurological deterioration without evidence of hemorrhage in a patient with a spinal arteriovenous (AV) malformation has been referred to as "Foix-Alajouanine syndrome." This clinical entity has been considered to be the result of progressive vascular thrombosis resulting in a necrotic myelopathy; it has therefore been thought to be largely irreversible and hence untreatable. The authors report five patients with dural AV fistulas who presented in this manner, and who improved substantially after embolic and surgical therapy. The outcome of these patients indicates that acute and subacute progression of myelopathy in cases of spinal dural AV fistulas may be caused by venous congestion and not necessarily by thrombosis. Therefore, a clinical diagnosis of Foix-Alajouanine syndrome is of little practical use, as spinal cord dysfunction from venous congestion is a potentially reversible process whereas thrombotic infarction is not. This diagnosis may result in suboptimal management. The recognition of nonhemorrhagic acute or subacute myelopathy as a complication of a spinal dural AV fistula is important since what appears to be irreversible cord injury is often treatable by standard surgical techniques. PMID- 2915244 TI - Prognostic importance of DNA ploidy in medulloblastoma of childhood. AB - The deoxyribonucleic acid (DNA) content of 53 medulloblastomas was analyzed by means of flow cytometry and compared with the clinical and histological findings in the host patients. Analysis of DNA showed that about half of the tumors were diploid and the other half were aneuploid. More diploid tumors were found among patients of a young age, but the difference was without statistical significance. Cellular differentiation of the tumor did not correlate with DNA ploidy. No correlation was found between Chang's T staging system and the DNA ploidy, whereas the M staging correlated with the ploidy; diploid medulloblastomas had a greater tendency to metastasize than aneuploid medulloblastomas (p = 0.0003). Four-year survival was compared with the extent of resection and DNA ploidy. The patients with total resection and aneuploid medulloblastoma had a better prognosis than those with subtotal resection and diploid tumor (p = 0.001). There was only one survivor among eight patients with subtotally resected diploid medulloblastomas, while all of the seven patients with totally resected aneuploid medulloblastomas survived. Comparison of the G0/G1 phase fraction and S phase fraction in the surviving group and the deceased group offered no significant information. PMID- 2915245 TI - The management of "asymptomatic" epidural hematomas. A prospective study. AB - Standard neurosurgical management mandates prompt evacuation of all epidural hematomas to obtain a low incidence of mortality and morbidity. This dogma has recently been challenged. A number of authors have suggested that in selected cases small and moderate epidural hematomas may be managed conservatively with a normal outcome and without risk to the patient. The goal of this study was to define the clinical parameters that may aide in the management of patients with small epidural hematomas who were clinically asymptomatic at initial presentation because there was no clinical evidence of raised intracranial pressure or focal compression. A prospective study was conducted of 22 patients (17 males and five females) aged from 1 to 71 years, who had a small epidural hematoma diagnosed within 24 hours of trauma and were managed expectantly. Of these, 32% subsequently required evacuation of the epidural hematoma 1 to 10 days after the initial trauma. Analysis of the patients revealed that age, sex, Glasgow Coma Scale score, and initial size of the hematoma are not risk factors for deterioration. However, deterioration was seen in 55% of patients with a skull fracture transversing a meningeal artery, vein, or major sinus, and in 43% of those undergoing computerized tomography (CT) within 6 hours of trauma. In contrast, only 13% of patients in whom the diagnosis of a small epidural hematoma was delayed over 6 hours subsequently required evacuation of the epidural collection. Of patients with both risk factors, 71% required evacuation of the epidural hematoma. None of the patients suffered neurological sequelae attributable to this management protocol. It was concluded that patients with a small epidural hematoma, a fracture overlaying a major vessel or major sinus, and/or who are diagnosed less than 6 hours after trauma are at risk of subsequent deterioration and may require evacuation. Conversely, patients without these risk factors may be managed conservatively with repeat CT and careful neurological observation, because of the low risk of delayed deterioration. PMID- 2915246 TI - Microsurgical reoperation following lumbar disc surgery. Timing, surgical findings, and outcome in 92 patients. AB - Ninety-two patients who underwent microsurgical reoperation for persistent or new complaints following initial lumbar intervertebral disc surgery were evaluated retrospectively. Sixty percent of all pain relapses occurred within 1 year following the first operation; thereafter, the probability of a relapse declined steadily and was as low as 0.1% per year between 5 and 20 years. The results of microsurgical reoperation in terms of pain relief and working capability were considered "excellent" in 22% of patients, "good" in 30%, and "satisfactory" in 29%. Thus, 81% of the patients could be considered as treated successfully and in 19% the result was not successful. The most common intraoperative findings were: a true recurrence at the same level in 43% of cases, a new herniation at another level in 15%, and a small recurrent fragment embedded in epidural fibrosis in 23%. Five percent of patients had severe epidural fibrosis as the only pathology. In 15%, reoperation was performed within 1 month to treat persisting pain, and either a missed disc fragment, an inadequately decompressed lateral recess, or an unrecognized second-level disc protrusion was found. The clinical outcome is affected predominantly by the intraoperative pathology and the time interval between the first and second operation. An excellent or good outcome was usually achieved in patients with a recurrence of pain after 1 year resulting from a true recurrent disc or a new herniation at another level. In contrast, very unfavorable results were noted with most reoperations performed during the 1st year when extensive epidural fibrosis (or fibrosis with a small recurrence) was present. PMID- 2915247 TI - One-stage posterolateral decompression and stabilization for primary and metastatic vertebral tumors in the thoracic and lumbar spine. AB - During the past decade, anterior approaches to the spine have been shown to be much more effective than laminectomy for the relief of pain and neurological deficits due to vertebral metastases. Laminectomy has failed because it does not allow adequate decompression of epidural lesions anterior to the thecal sac. In an effort to combine the advantages of the posterior approach with an adequate decompression, a one-stage posterolateral decompression-stabilization procedure was performed on nine patients with thoracolumbar spine tumors. The approach has been used for decompression and stabilization after thoracolumbar burst fractures. Marked lasting improvement was seen in all six patients with preoperative neurological deficits and in four patients with severe back pain and/or radiculopathy. Three nonambulators and two marginal ambulators could walk postoperatively without assistance. Of five patients who were working preoperatively, four returned full-time to their prior occupations. Three patients had serious complications, including one early postoperative death. No patient deteriorated neurologically due to the procedure. Although the series is small, it demonstrates that adequate one-stage decompression-stabilization of spinal epidural lesions is possible via the posterolateral approach and should be considered in certain cases as an alternative to the anterior approach. PMID- 2915248 TI - A comparison of the Minerva and halo jackets for stabilization of the cervical spine. AB - The motion at each intervertebral level permitted by the halo jacket and the thermoplastic Minerva body jacket was compared in 10 ambulatory patients with an unstable cervical spine. The thermoplastic Minerva body jacket is a new lightweight modification of a Minerva jacket which is fabricated from Polyform (a splinting material made of a polyester polycaprolactone) and Polycushion (a closed-cell foam for padding). Each patient served as his/her own control. The average movement from flexion to extension at each intervertebral level was significantly less in the thermoplastic Minerva body jacket (2.3 degrees +/- 1.7 degrees) than in the halo jacket (3.7 degrees +/- 3.1 degrees) (p less than 0.0025). This difference is attributable to the "snaking phenomenon" encountered with halo jacket immobilization and should be taken into account when considering an external splint for an unstable cervical spine. The thermoplastic Minerva body jacket also offered a substantial improvement in comfort for the patient over that experienced in the halo jacket. The apparent advantage with respect to stability and comfort of the thermoplastic Minerva body jacket over the halo jacket suggests that the former device is the orthosis of choice for ambulatory stabilization of most patients with an unstable posttraumatic cervical spine injury. PMID- 2915249 TI - Tic douloureux caused by primitive trigeminal artery or its variant. AB - Primitive trigeminal artery (PTA) is an extremely rare cause of tic douloureux. None of the reports on PTA variant, which is an anomalous cerebellar artery arising from the internal carotid artery without anastomosis to the basilar artery, has suggested the possibility of this vessel causing tic douloureux. Eight cases of tic douloureux are reported in which a PTA or PTA variant was found during microvascular decompression (MVD). These cases were derived from a series of 1257 patients treated with MVD for tic douloureux. In one patient, the neuralgia was caused by a combination of vessels: a PTA, the superior cerebellar artery, and the anterior inferior cerebellar artery. In the other seven cases, a PTA variant was compressing the root entry zone of the trigeminal nerve. All eight patients gained excellent pain relief after MVD of the root entry zone. The significance of PTA's and PTA variants as the cause of tic douloureux and the effectiveness of MVD in the management of such cases are discussed. PMID- 2915250 TI - Magnetic resonance imaging and aneurysm clips. Magnetic properties and image artifacts. AB - The magnetic properties of 12 different types of aneurysm clip were investigated in order to identify which clips allow postoperative magnetic resonance (MR) imaging without risk. Clip-induced MR artifacts were also quantitatively studied using a geometrical phantom. Nonferromagnetic aneurysm clips like the Yasargil Phynox, Sugita Elgiloy, and Vari-Angle McFadden clips do not appear to contraindicate MR studies performed with a FONAR beta-3000M imager. There is no clip movement upon introduction of the phantom into the MR imager, and the image artifacts caused by the clips are so limited that patients harboring such clips may well be considered for MR imaging. This examination may reveal information not obtainable by any other radiological modality. PMID- 2915251 TI - Proton magnetic resonance studies of triethyltin-induced edema during perinatal brain development in rabbits. AB - To better understand the role of myelin-associated water in the differentiation of white and gray matter in magnetic resonance (MR) imaging, changes in MR relaxation processes were studied in rabbits during myelination and after induction of cytotoxic edema with triethyltin (TET). Normal rabbits were killed at various age intervals ranging from premature (28 days' gestation) to adult, and changes in MR relaxation times (T1 and T2) and in water and electrolyte content were determined for various areas of brain and muscle. Similar measurements were made in rabbits of comparable age exposed to TET. Light and electron microscopy and MR imaging were used to follow myelin development and morphological changes induced by TET. During the first 30 postnatal days, both T1 and T2 declined by 50% in normal rabbits, a fall that paralleled the loss in brain water and sodium that occurred during the same period. Exposure to TET prolonged T1 and T2 in white but not gray matter, reflecting the accumulation of sodium and water (edema fluid) in white matter areas. Multiexponential analysis revealed a second, longer component in T2 magnetization decay of TET-exposed white matter, presumably attributable to accumulation of non-ordered water within intramyelinic vacuoles, a supposition consistent with electron microscopic and MR imaging findings. In contrast to reports by others, changes in T1 (but not T2) closely correlated with alterations in brain water (r = 0.93, df = 39). The absence of tissue disruption in the animals in the present study may account for these differences, but further studies will be required both to resolve this question and to fully understand MR images of white matter edema in mature and immature brain. PMID- 2915252 TI - Dissociated mesencephalic responses to medial and ventral thalamic nuclei stimulation in rats. Relationship to analgesic mechanisms. AB - To investigate the mechanism of analgesia noted with electrical stimulation of the thalamic sensory relay nucleus and medial thalamus, modulations of neuronal activities in the periaqueductal gray matter (PAG) were studied in response to electrical stimulations of the ventroposterolateral nucleus (VPL) and parafascicular nucleus (Pf) and to peripheral noxious stimulations in rats. Extracellular single-unit activities were recorded from 102 neurons in the PAG and the adjacent area in animals under halothane anesthesia. A large population (83%) of the PAG neurons reacted to Pf stimulations with a predominantly excitatory response, whereas smaller numbers (43%) responded to VPL stimulations. There was a significant correlation between the response characteristics of Pf and noxious stimulations, whereas no correlation was found between VPL and noxious stimulations. The PAG neurons that were verified antidromically to project to the nucleus raphe magnus showed a similar pattern of response. The excitatory response to the Pf stimulation was partially attenuated by systemic administration of naloxone, whereas that to the VPL stimulation was not affected. These results suggest that part of the analgesic mechanism of medial thalamus stimulation involves activation of the descending pain suppression system by exciting the PAG neurons through the opioid system, while the analgesia produced by sensory relay nucleus stimulation does not involve the PAG neurons or the opioid system. PMID- 2915253 TI - Papillary meningioma with pulmonary metastasis. Case report. AB - Successful surgical treatment by extirpation of remote metastases is extremely rare. A patient was admitted in whom multiple metastases to the lung occurred 8 years after extirpation of a papillary meningioma of the posterior fossa. The meningioma did not recur at the original site. The pulmonary metastases were surgically removed. The histological and electron microscopic findings of this case are presented. PMID- 2915254 TI - Profound hypothermia and circulatory arrest for aneurysm surgery. Case report. AB - Direct surgical repair of technically difficult or otherwise inoperable vascular lesions of the brain may become possible or safer using profound hypothermia and circulatory arrest. Most surgeons who use this technique establish extracorporeal circulation by cannulating the femoral vessels. To avoid difficulties associated with this closed chest method, a method was devised to establish extracorporeal circulation, profound hypothermia, and circulatory arrest by direct cannulation of the right atrium and aorta through the chest. This technique is described in a patient whose otherwise inoperable vertebral artery aneurysm was successfully treated. This approach is simple and offers several advantages over the closed chest method. PMID- 2915255 TI - Suprainguinal ligament approach for surgical treatment of meralgia paresthetica. Technical note. AB - For relief of meralgia paresthetica the authors have developed a suprainguinal ligament approach for decompression of the lateral femoral cutaneous nerve of the thigh. This proximal approach offers an alternative to the standard infraligament methods. Its chief advantage is that identification of the nerve trunk is easy and accurate. This avoids the tedious dissection involved in looking for small distal branches with their variable location. Lysis is easily performed, and angulation of the nerve in the iliac fossa is avoided. With this method, poor operative results can usually be eliminated. PMID- 2915256 TI - Cavernous angiomas and AVM's. PMID- 2915257 TI - Barbiturates in severe head injury. PMID- 2915258 TI - Treatment of Castleman's disease. PMID- 2915259 TI - Management of difficult basilar artery aneurysms. PMID- 2915260 TI - Optimum specimen positioning in the electron microscope using a double-tilt stage. AB - Optimal imaging of complex structures requires proper alignment relative to the optic axis of the electron microscope. This is especially important for high voltage and intermediate-voltage microscopes, which form an in-focus image throughout the entire thickness of the object. As a result, structures at different specimen heights form overlapping and confused images that severely curtail the usefulness of these instruments. The work described here provides a generalized, flexible method for optimizing specimen orientation and eliminating or limiting image overlap by means of a commonly used double-tilt stage. Analysis of the motion about the two axes provides accurate tilting for any azimuthal direction whether or not it corresponds to a mechanical axis of the stage. An object can be positioned to minimize image overlap, to record stereopairs for any parallax axis, and to record three-dimensional data sets by the conical collection geometry. Images of muscle paracrystals are shown after tilting about an axis perpendicular to a symmetry direction. The tilted image displays higher order symmetry, which is altered by changes of one degree. Precision double tilting for optimizing stereopairs is shown for a desmosome recorded using different parallax axes and pretilts. A tomographic conical data-collection scheme is demonstrated by imaging a microtubule axoneme for a specific cone half angle and arbitrary azimuthal angles. PMID- 2915261 TI - Determination of experimental and theoretical kASi factors for a 200-kV analytical electron microscope. AB - The relative sensitivity of an analytical electron microscope and energy dispersive x-ray detector to x-rays of various elements is investigated through an extensive kASi factor study. Elemental standards, primarily National Bureau of Standards multielement research glasses, were dry-ground into submicrometer-sized particles and analyzed at 200 kV accelerating potential. The effect of self absorption of x-rays by the particle has been corrected for, allowing the experimental kASi factors from this study to approximate those that could be obtained from "infinitely thin" specimens. Whenever possible, elemental k-factors were determined by the analysis of many (up to a maximum of nine) different standard materials. Experimental kASi factors were calculated for a wide range of K alpha, L alpha, and M alpha x-ray lines. For comparison, theoretical kASi factors, employing a variety of ionization cross sections, were computed. Good agreement is obtained between several of the theoretical k-factor models and the experimental results. Mass volatilization of Na and K from the small glass particles during analysis is discussed, as are observations that the grinding and/or dispersing of standard materials in a liquid (such as ethanol) may promote leaching of certain elements from the particle matrix. PMID- 2915262 TI - Preparation of cross-sectional transmission electron microscopy samples by electron beam lithography and reactive ion etching. AB - A cross-sectional sample preparation technique is described that relies on lithographic and dry-etching processing, thus avoiding metallographic polishing and ion milling. The method is capable of producing cross-sectional transmission electron microscopy samples with a large amount of transparent area (1 micron x 2.5 mm) which allows the examination of many patterned test sites on the same sample from the same chip of a silicon wafer. An example of the application of the technique is given for localized oxidation through a mask. PMID- 2915263 TI - Experimental conditions for surface microanalysis with reflection electron energy loss spectroscopy. AB - Experimental conditions for obtaining the optimum signal-to-background (S/B) ratio in reflection electron energy-loss spectroscopy (REELS) are investigated. It is shown that the S/B ratio can be improved by lowering the incident energy of the electrons. The spectra taken from the GaAs (660) specular reflection spot under the surface resonance condition is demonstrated to have the best S/B ratio and lowest surface plasma excitation, which is capable of providing structural information on the top few atomic layers. PMID- 2915264 TI - A new freeze-drying device for platinum replica studies of cell surface and cytoskeleton: an example using immunogold-labeled human erythrocytes. AB - We designed and built a freeze-drying device that ensures the protection of the specimens against contaminants during mounting on the cold stage of the freeze fracture machine, transferring into the vacuum chamber and deep etching. The device consists of a copper cap that covers the specimen and a thermal connection that ensures thermal transfer between the microtome arm and the copper cap. This device was used to study the ultrastructural features of the erythrocyte membrane skeleton and the immunocytochemical localization of spectrin in an "in situ" approach, by freeze drying and platinum rotary shadowing. Human erythrocytes adhered to polylysine-coated coverslips and were broken by a stream of buffer that mimics the intracellular ionic environment ("inside buffer"). The samples were prefixed in periodate-lysine-paraformaldehyde fixative, labeled with antispectrin 5-nm gold particles, fixed in glutaraldehyde, mordanted in tannic acid, postfixed in OsO4, repeatedly washed in water, rinsed quickly in 30% ethanol, freeze-dried, and rotary-shadowed. Electron microscopic examination of the replicas revealed the skeletal network on the inner surface of the erythrocyte membrane. Immunocytochemical labeling proved that spectrin represents a fibrillar component of the network. Our data confirm the speculative model of the molecular organization of the erythrocyte skeleton, based on studies on in vitro association of proteic constituents. Both the technique and the device developed by us may lead to a deeper understanding of the spatial organization of the cytoskeletal network of more complex cell types. PMID- 2915265 TI - Image analysis of electron micrographs relating to mineralization in calcifying cartilage: theoretical considerations. AB - Biological mineralization kis a cell-mediated process which is believed to be triggered by a "nucleating agent." Various matrix structures, such as matrix vesicles, collagen fibrils and macromolecules, have been claimed to be the source of this substance, since these components have been found by transmission electron microscopy (TEM) of thin sections to be associated with early mineral crystals. Systematic image analysis of the relationships revealed in electron micrographs between specific matrix components and early mineral deposits has shown that unequivocal image interpretation is not possible. This is due principally to the problems posed by overprojection and truncation phenomena, since the structures being analyzed lie within the same dimensional range as thin section thickness. Various examples are illustrated and discussed. The site at which mineral crystals are initially laid down thus cannot be identified with any matrix structure using thin section TEM. Possible technical approaches to resolve this problem of image analysis are discussed. PMID- 2915266 TI - An inexpensive detector for water-vapour in the low temperature scanning electron microscope. PMID- 2915267 TI - Identifying suicide potential in primary care. AB - This research addresses two issues concerning the role of primary care physicians in suicide prevention: 1) Are there signals in a patient's medical record that identify patients at increased risk of suicide? 2) Is the pattern of utilization of suicides immediately prior to suicide different from those of other patients? To address these issues, medical records data for suicides and for symptomatically depressed and non-depressed enrollees of an HMO were compared. Suicidal ideation and behavior, selected psychiatric diagnoses, and interpersonal problems were associated with suicide. However, information recorded in the medical record did not reliably discriminate suicides from controls. There were no substantial differences in the use of general medical services between the suicides and the controls. Less than 20% of the suicides visited a primary care physician in the month prior to death. Only 39% of suicides received specialty mental health treatment in the 18 months prior to death. PMID- 2915268 TI - A new instrument for patients' ratings of physician performance in the hospital setting. AB - A new instrument to elicit patients' appraisals of physician performance has been developed from a previously-derived taxonomy of desired physician attitudes and behavior. The instrument allows patients to give ratings for their physicians' discrete, observable items of behavior, and also for complex, multidimensional attributes. When the instrument was administered to 131 randomly chosen medical inpatients, the results showed that technical competence and interpersonal (or humanistic) qualities were equally valued, and that physicians received high ratings for most features of performance. Except for less satisfaction in younger patients, clinical and demographic characteristics had little impact on the ratings. The performance characteristics of the instrument appear satisfactory, and its potential applications and proposals for further research are discussed. PMID- 2915269 TI - Residents' decisions to breach confidentiality. AB - This study assessed variables involved in physician decisions to breach confidentiality in cases of patients' self-reported past crimes. Seventy internal medicine residents completed a questionnaire containing case vignettes of patients' self-reports of crimes; likelihood of informing the police was ascertained. Results were analyzed according to the type and cost of the crime, previous criminal record, patient characteristics, and intent of the patient to commit future crimes. Results also were analyzed by postgraduate year of the resident. Patient characteristics of race and socioeconomic status had no effect on the decision (p less than 0.122 and p 0.182), although age did (p less than 0.001). Reports of past violence (p less than 0.001), previous criminal record (p less than 0.001) and high-cost crime (p less than 0.007) increased the likelihood of breaching confidentiality. Future intent affected the decision (p less than 0.005), but less than reports of past violence. No differences were seen among postgraduate years of respondents (p less than 0.873). Residents base decisions to breach confidentiality on factors other than the future intent of specific violence. This finding has legal and ethical implications. PMID- 2915270 TI - AIDS prevention in primary care clinics: testing the market. AB - To assess attitudes toward educational programs about AIDS, 540 patients and 36 of their medical providers in primary care clinics were systematically sampled to ascertain what age groups should be exposed to a pamphlet entitled "Am I at Risk for AIDS?", as well as what was acceptable content for posters and pamphlets placed in clinic waiting rooms. Although fewer than 10% of patients and providers opposed asking both teenagers and adults to read a pamphlet listing risk groups and practices, 24% of patients and 51% of providers opposed exposing children to the pamphlets. Only 6% of patients and none of the providers opposed all posters about AIDS, but 30% of patients and 44% of providers opposed posters listing risk groups, and opposition was even greater to posters describing "safe sex." Regarding pamphlets acceptable for clinic waiting rooms, resistance among patients and providers was common (greater than 25%) only when sexual practices were specifically mentioned. Although 89% of patients stated they had never been asked about their sexual orientations by a doctor or nurse, 34% of providers stated that they "always" or "often" so inquire. In the primary care clinics surveyed, a wide variety of educational interventions about AIDS could be implemented with little opposition. PMID- 2915271 TI - Reliability of drug histories in a specialized geriatric outpatient clinic. AB - To examine the reliability of drug histories of elderly outpatients, records of 122 frail elderly patients in a geriatric outpatient evaluation clinic were reviewed. Drug histories were taken by an internist during an initial clinical evaluation and by a nurse practitioner during a home visit. Home and office drug lists disagreed in 39 cases (32%). Roughly equal numbers of "extra" drugs were listed in the two settings. Number of medications (especially two or more), number of active medical problems (especially four or more), and depression were significant, independent predictors of an unreliable drug history. Neither dementia nor living situation was a significant predictor of an unreliable drug history. The only drugs associated with an unreliable history were megavitamins, beta-blockers, and centrally-acting antihypertensive agents. Using the home list as the reference, there were equal numbers of omission errors and commission errors in the office drug histories. Strategies to optimize the reliability of office drug histories need further investigation. PMID- 2915272 TI - Relation of the pre-employment drug testing result to employment status: a one year follow-up. AB - All employees hired over a six-month period at a large hospital underwent pre employment urinary toxicology screening. Results of the screening were kept confidential. After a year of employment, the personnel folders of all employees studied were reviewed. Twenty-two of 180 employees (12%) had tested positive for drug use. Employees in clerical/aide positions were significantly more likely to test positive than were employees in professional positions (17% vs. 6%). Drug positive employees were also more likely to be young and male. Comparison of job performance variables, job retention, supervisor evaluations, and reasons for termination showed no difference between drug-positive and drug-negative employees. Eleven drug-negative employees were fired during the study; no drug positive employee was fired. There was a strongly significant difference between clerical and professional employees on each of these variables. This study did not find a relation between drug use and job performance. The widespread use of drug screening prior to employment makes further studies of this issue important. PMID- 2915273 TI - Medical art and medical science: an exhortation to students on primary care. PMID- 2915274 TI - Resolving the cost/access conflict: the case for a national health program. PMID- 2915275 TI - Screening for hemochromatosis? PMID- 2915276 TI - Clinical problems in adolescent medicine. PMID- 2915277 TI - Recognition of depression by internists in primary care: a comparison of internist and "gold standard" psychiatric assessments. AB - In an effort to elucidate the process of internists' recognition of depression in primary care settings, a comparison of internist and "gold standard" psychiatric assessments of patients was undertaken in a rural primary care practice over a 15 month period. Clinical characteristics and diagnoses, global assessments of psychosocial stress, and two aspects of chief-complaint presentation style, clarity and somatization, were recorded by the internists for each patient, who was independently assessed by a psychiatrist for the presence of any specific depressive disorder by structured interview. Internists correctly labeled 57% of the interview-assessed depressives as depressed; 13% of patients with "no psychiatric disorder" were assessed as depressed by internists. Clinical and demographic characteristics of the "false-negative" and "false-positive" internists' diagnoses were examined to clarify how internists think of "depression" in the primary care context. PMID- 2915278 TI - Substance abuse education during internal medicine training. PMID- 2915280 TI - Reviewing manuscripts reporting original research--do's and don'ts. PMID- 2915279 TI - Uncertainties in informed consent. PMID- 2915281 TI - The pediatrician's role in children's adjustment to divorce. PMID- 2915282 TI - Growth velocity, growth hormone therapy, and serum concentrations of the amino terminal propeptide of type III procollagen. AB - The relationship between serum concentrations of the amino-terminal propeptide of type III procollagen (PIIINP) and growth was assessed in 307 healthy subjects and 82 children with disorders of growth (41 with insufficient growth hormone, 23 with short stature and normal endocrinologic studies, 18 with tall stature) by means of a recently developed, simplified PIIINP radioimmunoassay. The PIIINP value appeared to be related to height velocity; in healthy children of each sex, the pattern of change with age mirrored the shape of the standard height velocity curve; in children with disorders of growth, there was a statistical correlation (p less than 0.001) between PIIINP concentration and height velocity. However, measurement of serum PIIINP alone had no diagnostic value because there was considerable overlap of PIIINP values in children with growth hormone insufficiency, short stature, normal stature, and tall stature. The most appropriate application of PIIINP may be in the monitoring of prepubertal children receiving exogenous growth hormone therapy; in these patients, increases in height velocity were reflected by increases in PIIINP, and early increases in PIIINP may have predictive value. PMID- 2915283 TI - Odontoid hypoplasia with vertebral cervical subluxation and ventriculomegaly in metatropic dysplasia. AB - Our experience with 12 patients with metatropic dysplasia has demonstrated two important and treatable complications: odontoid hypoplasia with subluxation of the first and second cervical vertebrae, and ventriculomegaly. Hypoplasia and lack of ossification of the odontoid process were noted in all cases. Subluxation of these two vertebrae was demonstrated in all six patients who had lateral flexion-extension radiographs; three had subluxation even in a neutral position, and sudden odontoid dislocation developed in another after a simple fall. Four individuals have had surgical fusion of the cervical vertebrae; one child died suddenly, 1 week before scheduled surgery. In the three patients in whom computed tomography scans of the head were obtained, enlarged ventricles were found; one had symptomatic increased intracranial pressure and required a shunt. We recommend that odontoid hypoplasia be evaluated in all patients with metatropic dysplasia. If subluxation is proved, atlantoaxial fusion should be performed before damage to the cervical part of the spinal cord results. Serial head circumference measurements and evaluation for hydrocephalus are also recommended. PMID- 2915284 TI - Relationship of procollagen type III propeptide-related antigens in serum to somatic growth in healthy children and patients with growth disorders. PMID- 2915285 TI - Inherited deficiency of ninth component of complement: an increased risk of meningococcal meningitis. PMID- 2915286 TI - Normal erythrocyte osmotic fragility in hereditary spherocytosis. PMID- 2915287 TI - Multicentric reticulohistiocytosis in a child. PMID- 2915288 TI - Clinical application of a new glucose analyzer in the neonatal intensive care unit: comparison with other methods. AB - We evaluated the operation of the Yellow Springs Instrument Co. (YSI) glucose analyzer (model 23A) by clinical nurses for the measurement of blood glucose in the intensive care nursery. In vitro performance was determined with the use of aqueous standards; with a 2-point calibration of 0.0 and 200 mg/dl, a precision of better than 1.0% of each standard (25, 50, 100, 200 mg/dl) was achieved, and the linearity was excellent (Y = 0.99X - 0.49, r = 0.99). The YSI correlated well with a manual spectrophotometric glucose oxidase method (r = 0.99) and the Kodak Ektachem analyzer (r = 0.98) using human umbilical cord blood samples. Five trained clinical nurses performed all YSI and glucose reagent strip analyses, including all in vitro and patient samples. Four reagent strip methods were compared with the YSI from 104 neonatal heel-stick blood samples: Glucometer II with memory (r = 0.73), Glucostix (r = 0.74), Dextrostix (r = 0.70), and Chemstrip bG (r = 0.83). We conclude that clinical nurses can and do learn to use the YSI with excellent precision and that the YSI represents an improved method for measuring glucose concentrations in the newborn intensive care nursery. PMID- 2915289 TI - Catch-up growth, muscle and fat accretion, and body proportionality of infants one year after newborn intensive care. AB - We studied catch-up growth, muscle and fat accretion, and body proportionality at 4 and 12 months of age corrected for prematurity in 30 very low birth weight (VLBW) (less than 1500 gm), 30 low birth weight (LBW) (1500 to 2499 gm) and 30 normal birth weight (greater than or equal to 2500 gm) infants who required newborn intensive care. At 4 and 12 months, the VLBW infants had significantly lower mean weight and length (p less than 0.01), but not lower occipitofrontal circumference percentiles, than the LBW and normal birth weight groups, and showed no catch-up weight or length growth between 4 and 12 months. All three groups had significant increases in mean upper mid-arm circumferences, mid-arm muscle circumferences, and arm muscle areas between 4 and 12 months. Mean mid-arm muscle circumferences and arm muscle areas were similar among the three groups at 4 months but became significantly stratified by birth weight groups by 12 months, with VLBW infants having the lowest mean value. In contrast, analysis of fat stores by triceps skin-fold thickness and arm fat area demonstrated no significant increases in any group between 4 and 12 months, except for arm fat area in the LBW group. The VLBW infants had significantly less fat than normal birth weight infants at 4 and 12 months. All three groups had proportional growth at both visits, as assessed by mid-arm circumference/head circumference ratio and weight-length percentile for age. The VLBW infants were significantly lighter for their length than normal birth weight infants. We conclude that VLBW infants have no first-year catch-up growth, remaining smaller than higher birth weight infants, although appropriately proportional. Somatic growth during the first year is due more to muscle than to fat accretion, especially in VLBW infants. PMID- 2915290 TI - Misalignment of lung vessels and alveolar capillary dysplasia: a cause of persistent pulmonary hypertension. AB - Two infants with fatal persistent pulmonary hypertension are described. Morphologically there was misalignment of the lung vessels, with the veins and the arterioles anomalously related, often sharing the same adventitial sheet. The capillaries did not make contact with the alveolar epithelium. The arterioles had increased medial muscle, and there was extension of the arteriolar muscularization to the precapillary level. The fraction of the parenchyma that was septal and connective tissue was increased. The acini had a decreased complexity, with immature alveoli and with a decreased radial alveolar count. The cause appeared to be related to abnormal capillary and venous plexus formation and migration. This syndrome seems to be identical with that described in three previous reports and probably represents a specific cause of persistent pulmonary hypertension. PMID- 2915291 TI - Effect of postnatal steroid administration on serum vitamin A concentrations in newborn infants with respiratory compromise. PMID- 2915292 TI - Large airway collapse in bronchopulmonary dysplasia. PMID- 2915293 TI - Intravenous immune globulin treatment of pulmonary exacerbations in cystic fibrosis. AB - The effect of intravenously administered immune globulin (IVIG) on patients with cystic fibrosis with an acute exacerbation of pulmonary infection was evaluated in a double-blind study. Patients at least 12 years of age, with chronic respiratory tract colonization with Pseudomonas aeruginosa and hospitalized with a reduction in pulmonary function, were randomly assigned to receive 20% dextrose (control subjects: n = 8) or 100 mg/kg IVIG (Gamimune) (experimental subjects: n = 8) on days 1, 2, and 3; all patients received intravenous antibiotics and chest physiotherapy. There were no differences between groups on admission; patients had moderate to severe disease as measured by Shwachman-Kulczycki scores and pulmonary function tests. Both groups improved clinically. The IVIG treatment was associated with significant increases in forced vital capacity and forced expiratory volume in 1 second (p less than 0.01) and with greater percent improvement in forced expiratory volume and forced expiratory flow (25% to 75%) (p less than 0.05). There was no effect on length of hospitalization (18.3 +/- 11.9 days control vs 17.6 +/- 6.5 experimental). The C3 level was decreased at discharge in IVIG-treated patients; circulating immune complex levels were unchanged. One patient in each group experienced side effects. There were no differences on follow-up at 6 weeks. We conclude that IVIG infusion early in treatment for pulmonary exacerbations in cystic fibrosis patients with moderate to severe disease may be associated with greater improvement in pulmonary function than standard treatment alone. PMID- 2915294 TI - Dose-response relationships of intravenously administered terbutaline in children with asthma. AB - The bronchodilator effect of three successive stable plasma terbutaline levels was studied in 10 children with asthma. Each terbutaline plateau was achieved by giving a rapid intravenous infusion of terbutaline, 0.9 microgram/kg, followed by a continuous infusion for 2 hours. Mean plasma terbutaline concentrations (18, 36, and 53 nmol/L at the three plateaus) were found to correlate linearly with the maintenance dose of terbutaline (2.4, 4.5, and 6.3 micrograms/kg/hr, respectively). Mean forced expiratory volume in 1 second increased from 65% to 96%, and mean forced mid-expiratory flow from 32% to 71% of the predicted normal value during the study (p less than 0.01); maximum bronchodilation was obtained at mean terbutaline levels of about 30 nmol/L (range 20 to 60). Effective plasma terbutaline levels were associated with side effects such as headache and tremor in all patients. In addition, heart rate increased from 84 to 116 beats/min, systolic blood pressure rose from 115 to 129 mm Hg, and diastolic blood pressure dropped from 72 to 61 mm Hg during the study. We conclude that a loading dose of 2 micrograms terbutaline per kilogram of body weight over 5 minutes, followed by a continuous infusion of 4.5 micrograms terbutaline per kilogram per hour, is suitable for treatment of severe bronchoconstriction in children. Because of interindividual variations in drug metabolism and clinical effect, dose adjustment should be evaluated at regular intervals. PMID- 2915295 TI - Oxandrolone therapy in six boys with the Prader-Willi syndrome. PMID- 2915296 TI - Outbreak of acute rheumatic fever in northern Italy. PMID- 2915297 TI - Brain biopsy for suspected herpes encephalitis. PMID- 2915298 TI - HIV-associated nephropathy. PMID- 2915299 TI - Penicillamine for lead poisoning. PMID- 2915300 TI - C-reactive protein in cystic fibrosis. PMID- 2915301 TI - Skin crease formation and lack of formation. PMID- 2915302 TI - Withholding nutrition from hopelessly ill infants. PMID- 2915303 TI - Definition of Leigh syndrome. PMID- 2915304 TI - Health care status of the Bedouin in Israel. PMID- 2915305 TI - Vitamin C-induced damage of erythrocytes in neonates. PMID- 2915306 TI - Carbon monoxide and flu-like symptoms. PMID- 2915307 TI - Medical management of orbital subperiosteal abscess in children. AB - The traditional treatment of subperiosteal orbital abscess consists of surgical drainage and antibiotic therapy. We successfully treated with antibiotics alone nine children (age range 26 months to 12 years) with clinical signs and symptoms of orbital cellulitis and computerized tomographic (CT) evidence of subperiosteal abscess and contiguous ethmoid sinusitis. Two additional patients successfully treated with nonsurgical therapy were identified retrospectively. All patients were admitted to the pediatric service with normal vision. Their visual function was assessed twice daily during the early stages of their illness. All patients improved with intravenous antibiotic therapy. One additional patient required surgical drainage for persistent pain after 1 week of slow but steady clinical improvement. All other patients were clinically cured with medical therapy alone. Five of the medical "cures" had posttreatment CT, which documented the resolution. No patient had a recurrence. We conclude that orbital subperiosteal abscess, like some other abscesses located elsewhere, may be amenable to non surgical treatment, or that these patients may have had a phlegmon rather than an abscess and the currently accepted CT criteria for diagnosis of a subperiosteal abscess may require modification. We recommend that children with a subperiosteal abscess from contiguous ethmoidal sinusitis who have no evidence of compromised optic nerve function be given a trial of intravenous antibiotic therapy prior to consideration of surgical drainage. PMID- 2915308 TI - Characteristics of the iris in 100 neonates. AB - To better characterize the appearance of the iris at birth, we studied certain iris features of 100 normal newborns with slit lamp biomicroscopy. We noted the iris color, crypt-structure, and vascularity of the collarette and periphery of the iris. These features were considered in light of the child's birthweight, postnatal days of age, sex, and race. Iris vascularity correlated significantly with postnatal age at examination, and stage of crypt development was more advanced in males, and more evident in the blue and gray irides. Males also had a more advanced stage of iris development. In addition to our previous finding that iris vessels of cocaine intoxicated neonates were more tortuous and dilated than a control group, this study suggests that such vessels may also be more commonly found in sickly infants. PMID- 2915309 TI - The use of two-stage Molteno implants in developmental glaucoma. AB - Developmental glaucoma, which cannot be controlled by conventional techniques, poses a difficult problem. Twenty-three eyes of 18 patients with developmental glaucoma underwent a two-stage implantation of the double template Molteno valve with follow-up between 12 and 84 months. The final pressure with medication was less than 21 mm Hg in 78% of the cases. These results were obtained in four out of four eyes with primary congenital glaucoma, six out of eight eyes with secondary congenital glaucoma, and eight of 11 eyes in which glaucoma followed surgery for congenital cataract. We feel that two-stage implantation of Molteno valves has a place in the management of difficult developmental glaucomas and is a reasonable early option when glaucoma occurs following surgery for congenital cataract. PMID- 2915310 TI - Hang-back lateral rectus recessions for exotropia. AB - The hang-back recession is a simple, safe alternative to conventional recession. We evaluated the surgical results in 23 consecutive patients undergoing bilateral hang-back lateral rectus recessions and 24 consecutive patients undergoing bilateral conventional lateral rectus recessions. The 6-week postoperative success rate was 78% in the hang-back group and 75% in the conventional group. At the time of the most recent follow-up, the success rate was 64% in the hang-back group and 85% in the conventional group. Dose-response curves were similar for both methods. There were more late overcorrections with the hang-back technique. We suggest modified surgical guidelines for the hang-back recession technique. PMID- 2915311 TI - Eyelid depigmentation following corticosteroid injection for infantile ocular adnexal hemangioma. AB - We report an unusual case of development of upper eyelid depigmentation in a child 4 months following corticosteroid injection of a periocular capillary hemangioma. Depigmentation has been described with local steroid injections for other dermatologic conditions, but has not been reported previously with treatment of infantile ocular adnexal hemangiomas. PMID- 2915312 TI - Conservative management of congenital nasolacrimal duct obstruction. AB - Fifty-nine children 1 to 24 months of age with congenital nasolacrimal duct obstruction (CNDO) were treated with local hydrostatic massage and antibiotic eye drops. Children 1 to 12 months of age showed a cure rate of 93.3%; only two of them underwent nasolacrimal probing. Children 13 to 24 months of age had a cure rate of 79.3%, and six underwent probing. The initial probings were successful in both age groups. Fifty-one children (86.4%) were thus spared nasolacrimal probing. PMID- 2915313 TI - Primary and secondary orbital teratomas. AB - Two patients with primary teratomas of the orbit and a third patient with a teratoma invading the orbit from the maxillary sinus are presented. The clinical presentation of each patient was spectacular. In the primary teratomas, the globe was displaced out of the orbit by the attached tumor, causing extreme proptosis. Computed tomography was virtually diagnostic, showing a variegated orbital mass with solid and cystic components. Histologic examination showed multiple tissues derived from two or three germinal layers. The surgical removal of the tumors and reasons for the poor visual outcome are discussed. The appearance of teratomas in the orbit and other cephalic structures appears to arise from the survival and proliferation of germ cells deposited there during embryogenesis. PMID- 2915314 TI - Acquired divergent strabismus: presumed metastatic gastric carcinoma to the medial rectus muscle. AB - A patient with rapidly progressive metastatic gastric carcinoma developed diplopia and diminished adduction of the right eye. The right medial rectus muscle belly was enlarged, as shown by computed tomography. This case is unusual, because gastric carcinoma comprises only 1% of orbital metastases and less than 5% of all orbital metastases localize to extraocular muscle. PMID- 2915316 TI - Child advocacy: the need is great. PMID- 2915315 TI - One versus two simultaneous goniotomies as the initial surgical procedure for primary infantile glaucoma. AB - To evaluate whether a more extensive incision of the tissue adjacent to the anterior trabecular meshwork resulted in more effective control of intraocular pressure (IOP), seven infants with bilateral congenital glaucoma underwent a single goniotomy in one eye and two simultaneous goniotomies at separate sites in the second. Sodium hyaluronate (Healon) was used in all eyes undergoing two simultaneous goniotomies and in three to seven eyes undergoing a single goniotomy. Success was not significantly different, at 1 month or 1 year postoperatively, for eyes which underwent two simultaneous and separate goniotomies. Successful control of IOP was, however, related to the preoperative IOP. Eyes for which the initial procedure was unsuccessful had a significantly higher IOP. The incidence of postoperative hyphemas was less in eyes in which the Healon was used intraoperatively, but the use of Healon did not favorably or adversely affect intraocular pressure control. PMID- 2915317 TI - Dispelling the common myths about pediculosis. AB - Pediculosis, the condition of being infested by head lice, is a major community health problem in the United States. Head lice, the most common species in humans, occupy considerable amounts of time and energy both within schools and the medical community. The condition creates school and family disturbances and personal embarrassment--consequences far exceeding its medical effects. Because parents are often embarrassed when they are informed about a head lice infestation, they often do not approach the subject with their health care providers. Pediatric nurse practitioners (PNPs) need to incorporate education relating the diagnosis and management of pediculosis in the well child visit. PNPs can dispel the common myths that have existed for so long to help open communication with parents and children to promote safe and proper treatment. Early detection is vital in preventing epidemics. PMID- 2915318 TI - Preventing the perinatal spread of hepatitis B. PMID- 2915319 TI - Sibling rivalry. PMID- 2915320 TI - Cytochemical demonstration of lysosomes in the chicken pineal gland: changes induced by light-dark cycle. AB - Light and electron microscopic demonstrations for acid phosphatase (AcPase) activity in the chicken pineal gland were studied with special reference to the changes induced by the light-dark cycle. AcPase-positive lysosomes and Golgi cisternae and vesicles located in the pinealocyte in the light period are well developed and more numerous than in the dark period. In a few cases, a type of lysosome wrapping mechanism is present in the pinealocyte during the light period. Therefore, the lysosomes in the chicken pinealocyte appear active during the light period. In addition, the lysosomes may have functional relationships with the lipid-like inclusions seen in the dark period. PMID- 2915321 TI - Stereological changes in rat ventral prostate induced by melatonin. AB - Effects of melatonin on the ventral prostate of castrated rats supplemented with testosterone were studied using light microscopy. Stereological measurements were made of volume fractions of acini and stroma and surface fractions of glandular epithelium. From these figures and the weights of the glands, the volumes and surface areas were calculated, as well as the mean epithelial heights, mean acinar diameters, and mean distances between glandular acini. Doses of melatonin were varied, to verify its physiological and pharmacological effects. Castration without hormonal treatments produced atrophic changes, with decreases in acinar and stromal volume and widenings in the mean distances between the acini. None of these measurements differed among intact controls, sham-operated controls, and testosterone-supplemented castrated rats. In the castrated rats receiving both testosterone and melatonin, however, there were changes according to the doses of melatonin given. The animals receiving low doses of melatonin (50 and 400 micrograms daily) showed significant decreases in the volumes of the stroma and epithelium and the height of the epithelium. These stereological changes occurred without a significant reduction in the prostatic weights. The animals receiving the higher dose (800 micrograms daily) of melatonin showed no difference in any measurement compared with those of the testosterone-supplemented castrated rats. In rats receiving 2,000 micrograms of melatonin daily, there were significant reductions in the weights of the prostates and the volumes of the acini. These results suggest a direct action of melatonin on the ventral prostate, and the effects depend on the dose given. PMID- 2915322 TI - Preliminary evidence for pineal-mediated extraretinal photoreception in relation to tail regeneration in the Gekkonid lizard, Hemidactylus flaviviridis. AB - The tail of the Gekkonid lizard Hemidactylus flaviviridis was autotomized and the animals were subjected to eight different photoperiodic schedules during the process of tail regeneration. Our previous observation had shown that long-day photoperiods stimulate the regeneration process, whereas short-day photoperiods depress it. Furthermore, it has also been demonstrated that the lateral eyes, or retinae, do not participate in photoperiodically significant photoreception in H. flaviviridis, as blinded Hemidactylus regenerated their autotomized tails like their sighted counterparts exposed to similar experimental photoregimes. In a further attempt to localize the site(s) of photoreception in these animals, one group of lizards had their heads painted with a mixture of Indian ink and Nile blue sulphate (II-NBS) [NL (HP)] in order to prevent light from penetrating to the pineal gland, and another group had their pineal glands surgically removed (pinealectomy, Px); the regenerative potentials were compared with their normal (NL) counterparts. Our results showed that the initiation and onset of regeneration, the daily growth rate, the total new growth (regenerate) produced at the end of regeneration and the total percentage replacement of the lost (autotomized) tails were significantly retarded in Px and NL (HP) animals, compared with the NL (unoperated and nonpainted) ones. Since pinealectomy as well as light deprivation to the pineal abolished the stimulatory influence of long length photoperiods, the pineal gland is discussed here as a major transmitter of photic stimulus in lacertilian tail regeneration. It is presumed that in the lizard, as in mammals and some birds, the pineal gland acts by way of the neuroendocrine complex and/or the hypothalamohypophyseal axis. PMID- 2915323 TI - Presence of melatonin in the umbilical cord blood of full-term human newborns. AB - The present study was designed to determine whether melatonin circulates in the umbilical cord blood of healthy human newborns and whether the concentrations of this hormone follow a circadian rhythm at birth. Umbilical cord blood was collected from full-term human newborns at the time of delivery. Serum melatonin was extracted with diethylether and determined by radioimmunoassay by using radioiodinated melatonin and rabbit antimelatonin antiserum. Significant amounts of melatonin were detected in the sera obtained from umbilical cord blood. When serum melatonin concentrations of human newborns were represented over 6-h periods or hour by hour over the 24 h of 1 d, similar hormone concentrations were found consistently. These results indicate that melatonin is present in quite high levels in the umbilical cord blood, which may be, at least in part, of maternal origin. Also, our results suggest the absence of a melatonin circadian rhythm in human newborns, which may reflect an immaturity of the components involved in melatonin synthesis. PMID- 2915324 TI - Human melatonin suppression by light is intensity dependent. AB - Five intensities of artificial light were examined for the effect on nocturnal melatonin concentrations. Maximum suppression of melatonin following 1 hr of light at midnight was 71%, 67%, 44%, 38%, and 16% with intensities of 3,000, 1,000, 500, 350, and 200 lux (lx), respectively. In contrast to some previous reports, light of 1,000 lx intensity was sufficient to suppress melatonin to near daytime levels, and intensities down to 350 lx were shown to significantly suppress nocturnal melatonin levels below prelight values. On the basis of these data, it is suggested that when examining the melatonin sensitivity of patient groups (such as bipolar affective disorders) to artificial light, an appropriate light intensity should be established in each laboratory. Light of less intensity (e.g., 200-350 lx) may be more suitable to dichotomize patient groups from control subjects. PMID- 2915325 TI - Seasonal variation in the daily pattern of plasma melatonin in a wild mammal: the mountain hare (Lepus timidus). AB - Seasonal differences in daily patterns of plasma melatonin concentration were investigated in both free-living and captive mountain hares, in relation to reproductive activity. There was a marked increase in plasma melatonin concentrations at night at all times of the year. The period of elevation of plasma melatonin above the daytime values was longer in winter than in summer, correlating with the longer duration of darkness. The magnitude of the nighttime rise in melatonin concentrations did not differ significantly between seasons. There was no change in the plasma melatonin profile under similar photoperiods before the summer solstice when hares are sexually active or after the summer solstice when gonadal regression occurs, indicating that melatonin is not directly pro- or antigonadal. These field and laboratory observations support the view that the daily rhythm of melatonin secretion plays a role in the transduction of photoperiodic information in the mountain hare. Furthermore, they favor the hypotheses that the circadian melatonin rhythm transduces photoperiod information by means of the duration of nocturnal melatonin secretion or by the coincidence of elevated melatonin with a particular sensitive period, rather than by the amplitude of the nocturnal rise. PMID- 2915326 TI - On the uptake and incorporation of thymidine by cultured chick pineal glands. AB - Cultured chick pineal glands showed a marked cycle in the incorporation of thymidine into DNA. They also accumulated exogenous thymidine in one, or more, endogenous thymidine pool(s). However, there was no significant variation in ability to take up thymidine during incubation with either standard medium or media of increased thymidine content. We could not eliminate the possibility of variation in size of a quantitatively minor, but metabolically extremely important, thymidine pool which "channels" precursor directly into DNA. PMID- 2915327 TI - On thymidine incorporation by the cultured chick pineal gland. AB - Explanted chick pineal glands exhibited a cycle in thymidine incorporation when cultured either under a cycle of illumination or in constant darkness. This cycle appeared to be entrained to the light cycle under which the birds were maintained. The incorporation reflected gene replication in a small fraction of the cell population that was largely, but not entirely, located in the stroma of the gland. Glands cultured with colchicine for 28 h contained a very small number of cells showing metaphase chromosomes. PMID- 2915328 TI - Radiographically detectable intraoral positional radiation stent. PMID- 2915329 TI - Method for denture identification. AB - Steps for using a plastic chip to identify a removable prosthesis are described. PMID- 2915330 TI - Microleakage at the gingival margin of class II composite restorations with glass ionomer liner. AB - Microleakage at the gingival margins is a major problem with class II posterior composite restorations. Gingival margins of class II restorations with a glass ionomer cement liner were evaluated for in vitro microleakage. At the end of 1 year less microleakage occurred at the gingival margin of class II restorations when a glass-ionomer cement was used as a liner. PMID- 2915331 TI - A comparison of the physical properties of four prosthetic veneering materials. AB - Four resin materials used to veneer metal castings were compared by evaluating certain physical properties. Three of the materials were microfilled resins and one was an unfilled resin. Although no material proved to be superior in all of the tests, the microfilled materials were generally better than the unfilled materials. The heat- and pressure- polymerized microfilled material was inferior to the two light-polymerized microfilled materials in three of the physical property tests, superior to them in one test, and proved to be equivalent to them in two tests. PMID- 2915332 TI - Comparison of casting ability of castable ceramic and type III gold. AB - This study compared the property of castability of a castable ceramic to an American Dental Association-certified type II casting alloy. A wax pattern was made with a manifold-type structure from which monofilament lines projected approximately 5 to 6 mm. The diameter of the nylon lines ranged from 132 micron to 1270 micron. Each pattern was invested and cast according to the manufacturer's specifications. Each casting was divested and measured for length of casting of the monofilament on a measuring microscope. The castable ceramic and type II gold cast completely at diameters of 1270 micron, and 724 micron, but only type II gold cast completely at the 152 micron and 132 micron diameters. PMID- 2915333 TI - An efficient method for constructing a soft interocclusal splint. AB - A silicone rubber interocclusal splint can be made chairside in a few minutes and can be used in a variety of situations including MPD syndrome. A step-by-step technique is presented. Soft interocclusal splints are not intended to replace splints of hard plastic, but rather to supplement them. PMID- 2915335 TI - Presurgical radiographic assessment for implants. AB - A radiographic technique was developed to accurately assess bone available for the placement of intraosseous implants. Hypocycloidal tomographs were made at right angles to the long axis of the mandibular and/or maxillary alveolus while the patient was wearing a specially designed splint. Alveolar height and width measurements were obtained from the resulting films. Sensitivity results for this technique showed that the mean difference between the actual bone height and width and that measured in the radiographs was 0.49 mm and 0.35 mm, respectively. A paired difference test revealed a range of 0.25 mm to 0.73 mm in the expected error in the height and 0.20 mm to 0.50 mm in width measurements with a 95 confidence interval. PMID- 2915334 TI - Relationship of the maxillary canines to the incisive papilla. AB - The positioning of denture teeth in a completely edentulous patient is dependent on many factors. Anatomic landmarks are frequently valuable in complete denture fabrication. The topography of the palatal soft tissue in relationship to tooth position in dentate patients may be an aid in the placement of denture teeth. By using casts formed from irreversible hydrocolloid impressions, 50 subjects were examined to determine the orthographic distance from the posterior of the incisive papilla to a line intersecting the distal contact points of the maxillary canines. In 92% of subjects the posterior point of the incisive papilla was approximately 3 mm anterior to the line between the distal points of the canines. Neither gender, age, nor maxillary tooth arch form affected this distance. PMID- 2915336 TI - Stabilization technique for mobile teeth. AB - A new technique for immobilization of teeth uses inexpensive, readily available, medically acceptable, and biocompatible nylon thread. Three monofilament nylon threads of sizes between Nos. 25 and 40 are interwoven to a braid to form, along with the threaded pins, the stabilization media. A channel along the stabilized teeth is prepared; the braid is placed in it and fastened onto the teeth with the help of pins, which are threaded on them through the braid. The advantages of this method are also presented and discussed. PMID- 2915337 TI - Pulp test response of the maxillary anterior teeth in cleft palate patients. AB - The relative pulpal responsiveness of the six maxillary incisors to electrical and cold thermal stimuli was tested in patients with complete unilateral and bilateral clefts. The six maxillary anterior teeth were tested at random to electrical stimuli. After a 5-minute interval, the same teeth were tested at random to cold stimuli with an ice pencil. Unilateral and bilateral cleft palate patients had statistically significant higher mean electrical pulp test thresholds for the maxillary anterior teeth than the noncleft palate patients. No statistically significant difference between unilateral and bilateral cleft palate patients was found in electric pulp test responses of the maxillary anterior teeth. No statistically differences in electric pulp test responses and cold test responses of the maxillary anterior teeth in both cleft palate and noncleft palate individuals based on differences in sex were observed. No statistically significant difference in cold test responses were observed between cleft palate and noncleft palate patients. Cleft palate patients who completed orthodontic treatment within 1 year of testing showed elevated mean electrical pulp test thresholds as did noncleft palate patients who received orthodontic treatment within 1 year of testing. PMID- 2915338 TI - Subjective symptoms in patients with temporomandibular joint disk displacement versus patients with myogenic craniomandibular disorders. AB - Signs and symptoms in the masticatory system can be caused by several specified diseases leading to diagnostic problems. This investigation compared patients with temporomandibular joint disk displacement and patients with complaint of myogenic craniomandibular disorders. In association with the onset of the patient's problem, a physical event was found in half the number of patients with permanent disk displacement, compared with only 27% in the myogenic craniomandibular disorders group. Patients with permanent disk displacement reported more pain in the temporomandibular joint ear and jaw region in association with jaw function whereas patients with myogenic craniomandibular disorders reported more bruxism and dental discomfort. PMID- 2915339 TI - Graphic tracings of condylar paths and measurements of condylar angles. AB - A study was carried out to determine the accuracy of different methods of measuring condylar inclination from graphical recordings of condylar paths. Thirty subjects made protrusive mandibular movements while condylar inclination was recorded on a graph paper card. A mandibular facebow and intraoral central bearing plate facilitated the procedure. The first method proved to be too variable to be of value in measuring condylar angles. The spline curve fitting technique was shown to be accurate, but its use clinically may prove complex. The mathematical method was more practical and overcame the variability of the tangent method. Other conclusions regarding condylar inclination are outlined. PMID- 2915340 TI - Therapeutic holding. Effective intervention with the aggressive child. PMID- 2915341 TI - Alcoholism. Prevention and treatment. PMID- 2915342 TI - Crosstalk. Assimilation of conflicting information among mental health professionals. PMID- 2915343 TI - Invasion. A hospital in transition following the 1983 Grenadian intervention. AB - Stress, confusion, and a sense of loss were inevitable during the hospital relocation, especially given the large number of clients, ward communities, and staff needed to move and adjust to change. Despite the fact that the change was perceived as a positive and progressive step in psychiatric-mental health care in Grenada, there were many obstacles and much resistance to overcome. As expected, staff's and clients' fears centered around themes of impending loss and abandonment. An understanding of the transition process, along with the availability of experienced hospital staff for support and guidance, greatly aided the relocation process. Relocation still presented problems and Mt. Gay Hospital continues to struggle to carry out the lasting and beneficial changes that will best promote a therapeutic and culturally sensitive client/staff environment. Despite the fact that the hospital relocation was not entirely self determined, but partially imposed by political circumstances, a positive resolution of the crisis occurred. The crisis brought about the change that, in this circumstance, is seen as synonymous with growth. It acted as a catalyst to bring about help from unexpected and much needed sources (U.S.A.I.D./Project Hope), which may not have otherwise been available to facilitate such a change. Richmond Hill Mental Hospital took control and advantage of a crisis situation and made it serve its immediate and pressing need for a new psychiatric hospital. PMID- 2915344 TI - How families cope. PMID- 2915345 TI - Direct identification of the rat hepatocyte arginine8 vasopressin receptor with a radiolabelled V1-selective antagonist. AB - We compared [3H] arginine8 vasopressin (AVP) and [3H] 1-beta-mercapto-beta, beta cyclopentamethylene propionic acid, O-methyl tyrosine2, arginine8 vasopressin (d(CH2)5 Tyr(Me)AVP), a selective V1 receptor antagonist, as radioligands for the rat hepatocyte V1 receptor. Both radioligands bound with high affinity to a site in partially purified membranes prepared from Long Evans rat hepatocytes. The binding site concentrations obtained with either radioligand, 608 +/- 101 fmol/mg protein (n = 5) with [3H] AVP and 603 +/- 62 fmol/mg protein (n = 5) with [3H]d(CH2)5 Tyr(Me)AVP, were not significantly (p greater than 0.5) different. Furthermore, the rank order of potency of a series of synthetic vasopressin analogs and related peptides were identical in competition studies using either radioligand and were consistent with a V1 receptor interaction. Our results demonstrate that [3H] d(CH2)5 Tyr(Me)AVP is a suitable radioligand to study the V1 receptor subtype. PMID- 2915346 TI - Competitive interaction of agonists and antagonists with 5-HT3 recognition sites in membranes of neuroblastoma cells labelled with [3H]ICS 205-930. AB - [3H]ICS 205-930 labelled 5-HT3 recognition sites in membranes prepared from murine neuroblastoma N1E-115 cells. Binding was rapid, reversible, saturable and stereoselective to an apparently homogeneous population of sites. Kinetic studies revealed that agonists and antagonists produced a monophasic dissociation reaction of [3H]ICS 205-930 from its recognition sites. The dissociation rate constant of the radioligand was similar whether the dissociation was induced by an agonist or an antagonist. Competition studies carried out with agonists and antagonists also suggested the presence of a homogeneous population of [3H]ICS 205-930 recognition sites. Competition curves were best fit for a 1 site model. [3H]ICS 205-930 binding sites displayed the pharmacological profile of a 5-HT3 receptor. The interactions of agonists and antagonists with [3H]ICS 205-930 recognition sites were apparently competitive in nature, as demonstrated in kinetic and equilibrium experiments. In saturation experiments carried out with [3H]ICS 205-930 in the presence and the absence of unlabelled agonists and antagonists, apparent Bmax values were not reduced whereas apparent Kd values were increased in the presence of competing ligands. There was a good agreement between apparent pKB values calculated for the competing ligands in saturation experiments and pKd values calculated from competition experiments. The present data demonstrate that [3H]ICS 205-930 labels a homogeneous population of sites at which agonists and antagonists interact competitively. PMID- 2915347 TI - Potassium depletion and regulation of angiotensin II receptors in vascular smooth muscle cells. AB - Mesenteric artery smooth muscle cells were grown in culture media containing high, normal, or low concentrations of potassium to study the effects on angiotensin II (Ang II) receptor regulation. Cell growth was similar among cells grown in the different culture media. Cells grown in high potassium media (K = 5.8 mEq/L) had an equilibrium dissociation constant, Kd, of 1.59 +/- 0.2 nM, whereas those grown in normal potassium media (K = 4.1 mEq/L) had a Kd of 1.79 +/ 0.2 nM and those grown in a low potassium media (K = 2.9 mEq/L) had a Kd of 1.19 +/- 0.12 nM (not significantly different, NS). Binding capacity of smooth muscle cells grown in high potassium media was 81 +/- 16.7 fmol/mg prot, 95.1 +/- 12.4 fmol/mg prot in those grown in normal potassium media and those grown in low potassium media 86.4 +/- 24.1 fmol/mg prot (NS). Binding of radiolabelled Ang II was reduced by approximately 70% in cells exposed to unlabelled Ang II for 30 or 60 minutes. However, this effect of exposure to Ang II to reduce subsequent binding of Ang II was identical in cells grown in high and low potassium medium. Therefore, we were unable to identify a direct effect of low potassium to induce changes in Ang II receptor binding affinity or binding capacity. Previously observed changes in these Ang II binding parameters in potassium-depleted rats was probably a consequence of other factors which were simultaneously altered by potassium deficiency. PMID- 2915348 TI - Estimation of the relative fertilizing ability of frozen chicken spermatozoa using a heterospermic competition method. AB - Semen was collected from Rhode Island Red and White Leghorn roosters. After adjusting the sperm number from both breeds, half of the semen was frozen-thawed in the presence of glycerol. Frozen and unfrozen semen from both breeds was mixed 1:1 with all four possible combinations and inseminated into Rhode Island Red hens. Feather colour of chicks was used to determine which breed fertilized the eggs. Results showed that sperm cells retained 19.7% [95% confidence interval = (12.8, 30.4)] of the relative fertilizing ability after freezing. Furthermore, Rhode Island Red spermatozoa had 1.5 times [95% confidence interval = (1.1, 2.0)] higher relative fertilizing ability than did White Leghorn spermatozoa. The heterospermic competition assay method is a powerful tool for estimating the relative fertilizing ability of the sperm cells. PMID- 2915349 TI - Immunohistochemical investigation of secretory component and immunoglobulin A in the genital tract of the female rat. AB - There was intense labelling of secretory component (sc) in the glandular and luminal epithelia of the uterine horns at pro-oestrus, oestrus and Day 1 of pregnancy, but at other stages labelling was weak or undetectable. There was also intense labelling of sc in the superficial layer of cells in the stratified epithelia of the cervix and vagina at pro-oestrus and Days 4-7 of pregnancy, but not at other stages. Plasma cells containing immunoglobulin A (IgA) were not observed in any region of the genital tract at any of the times studied. The presence of sc coupled with an absence of IgA-containing plasma cells suggest that IgA in genital tract secretions of the female rat may be derived mainly from serum. PMID- 2915350 TI - Reproduction of Angola free-tailed bats (Tadarida condylura) and little free tailed bats (Tadarida pumila) in Malawi (Central Africa) and elsewhere in Africa. AB - Angola free-tailed bats and little free-tailed bats occur in diverse habitats throughout most of Africa south of the Sahara. This study investigated the reproductive strategies and related biology of these species in Malawi where they were sympatric, and analysed data from elsewhere in Africa to show how the strategies varied along a gradient of habitats from approximately 12 degrees N to 25 degrees S. Both the Angola free-tailed bat and the little free-tailed bat were normally monotocous. Angola free-tailed bats invariably had 2 births/year, and the interval between consecutive births decreased with increasing latitude. When the interval was shortest (approximately 90 days) a post-partum oestrus occurred. Little free-tailed bats differed by having a shorter gestation (approximately 60 days), and the ability to have up to 5 births/year with a postpartum oestrus after each birth. The extent to which this potential is achieved varies with latitude and rainfall, mainly so that lactation can coincide with peaks in the abundance of food. The interaction between rainfall and reproductive characteristics results in the two species having patterns of reproduction which are sometimes similar, but more often different. Competition between the species is unlikely to be affected by differences in their reproduction. PMID- 2915351 TI - Quantitative autoradiographic study of FSH binding sites in prepubertal ovaries of three strains of rats. AB - Iodinated FSH was injected to 18- and 36-day-old rats of 3 strains (03, 04 and 12) with different sensitivity to FSH (12 less than 03 less than 04) and autoradiography was performed on histological sections of the labelled ovaries. Specific labelling was quantified by microphotometry on histological slides, on granulosa cells of individual follicles with different sizes (greater than 80 micron diameter) and qualities. In small preantral follicles (less than 160 micron diameter) the labelling was low and homogeneous within the granulosa; it increased between 18 and 36 days of age in the 3 strains. At 36 days, ovaries were characterized by the presence of large preantral and antral follicles with a higher labelling in the outer layers of granulosa (near the theca), compared to the inner layers. In definitely atretic follicles, a loss of binding sites was detected in the outer layers. In rats of Strains 03 and 04, the number of binding sites for FSH in the outer layers of granulosa of follicles with a diameter of greater than 160 micron increased with follicular size; no change was detected in follicles of Strain 12 rats. The low number of binding sites for FSH and the lack of terminal maturation which characterize the follicles of strain 12 rats can be related to the poor and delayed follicular development, the low sensitivity to exogenous FSH and the low fertility of the animals of this strain. PMID- 2915352 TI - Survival of day-4 embryos from young, normal mares and aged, subfertile mares after transfer to normal recipient mares. AB - The estimated embryonic loss rate between Days 4 and 14 after ovulation for young, normal mares (9%) was significantly lower (P less than 0.01) than the estimated embryonic loss rate for aged subfertile mares (62%). Fertilization rates, which were based on the recovery of embryos at Day 4 after ovulation, were 96% and 81% (P less than 0.1) for normal and subfertile mares, respectively. Day 4 embryos were collected from the oviducts of normal and subfertile donors mares. These embryos were transferred to the uteri of synchronized, normal recipient mares to test the hypothesis that the high incidence of embryonic loss in subfertile mares was related to embryonic defects. The hypothesis was supported because embryo survival rates were significantly higher (P less than 0.05) for Day-4 embryos from normal compared to subfertile mares. These defects may have been intrinsic to the embryo or might have arisen due to the influence of the oviducal environment before Day 4 after ovulation. PMID- 2915353 TI - Contraception in mares heteroimmunized with pig zonae pellucidae. AB - Ten fertile feral mares and 6 domestic horses (4 fertile mares, 1 infertile mare, 1 gelding) were immunized with heat-solubilized pig zonae pellucidae by 4 injections equivalent to 2000 or 5000 zonae each at 2-4-week intervals and a booster injection of 20,000 zonae 6-10 months after the last of the initial inoculations. The immune response was reflected by high antibody levels as measured by an enzyme-linked immunosorbent assay (ELISA) using immobilized pig zona antigen. In-vivo inhibition of fertility occurred in 12 (86%) of the 14 fertile mares studied and persisted for a minimum of 7 months. Repeated mating of the fertile domestic mares resulted in conception when anti-pig zona antibody concentrations had decreased from initial peak absorbance ratios (greater than 1.0) to relatively lower levels (0.64 or less with one exception). An indirect immunofluorescence assay, revealed a considerably lower cross-reactive antibody titre with horse oocytes as compared to pig oocytes. Clinical, endocrinological and histological analyses of the ovaries and their function following regained fertility after immunization revealed no abnormalities. One mare remained infertile. PMID- 2915354 TI - Time of the sidereal year affects responsiveness to the phase-resetting effects of photoperiod in the ewe. AB - Two groups of ovary-intact ewes were placed in separate photochambers on the day of the vernal equinox (VE). One group was exposed to a 16 h light:8 h dark (16L:8D) photoperiod and the other to 8L:16D. On the day of the summer solstice (SS) and at 90-91-day intervals thereafter [autumnal equinox (AE), winter solstice (WS), VE and SS], each group was changed to the opposite photoperiod. The latent period between each change and either onset or cessation of cycles, as determined by measuring blood progesterone concentrations, was recorded. The latent period between change to 8L:16D and onset of cycles was shortest after the exposure at AE and longest after exposure at WS (P less than 0.001). The latent period after AE was shorter (P less than 0.001) than after VE. The correlations were small between ambient temperature and interval to onset of cycles. The latent period to cessation of cycles in response to 16L:8D was shorter after SS exposure than after WS exposure (P less than 0.01), but other differences were not significant. There was a strong (r = -0.94, P less than 0.05) negative correlation between interval to cessation of cycles and ambient temperature. Cessation of cycles in response to 16L:8D occurred more rapidly (P less than 0.001) than onset in response to 8L:16D. These results show that responsiveness to the inductive effects of photoperiod varies significantly with time of the sidereal year. PMID- 2915355 TI - Does inadequate luteal function limit the establishment of pregnancy in the early post-partum ewe? AB - In Exp. 1 the effect of lactation versus early weaning on luteal function was examined in seasonally anoestrous Finn Dorset ewes that were induced to ovulate at 21 (N = 14) or 35 (N = 14) days post partum by using a CIDR device and PMSG. Prolactin concentrations were significantly higher (P less than 0.001) in lactating compared with early weaned ewes throughout the study. The proportion of lactating ewes with inadequate luteal function (as assessed by daily progesterone concentrations) in the 21-day group was 0.43 (3 or 7) compared with 0.67 (4 of 6) for those weaned within 2 days after parturition. Corresponding values for the 35 day group were 0 (0 of 4) and 0.14 (1 of 7) respectively. There was no evidence of abnormal luteal function in standard ewes (N = 8) for which the interval from parturition was greater than 150 days. In Exp. 2 we examined whether pregnancy can be successfully established during the breeding season following transfer of embryos into lactating or early weaned ewes in the early post-partum period. Embryos were donated from Border Leicester x Scottish Blackface ewes for which the interval from previous parturition was greater than 150 days. These embryos were transferred synchronously on Day 5 after behavioural oestrus to recipient ewes with the same breeding history as the donors (standard ewes, N = 15) or to lactating or early weaned recipients that had been induced to ovulate on Day 21 (N = 16) or 35 (N = 24) post partum. In the 21-day group inadequate luteal function was observed in 2 of 7 (0.28) lactating and 4 of 9 (0.44) early weaned ewes compared with corresponding values of 1 of 13 (0.08) and 2 of 11 (0.18) in the 35-day post-partum group. Luteal function was normal in all standard ewes. The proportion of successful pregnancies in the standard ewes was 0.80 (12 of 15) compared with 0 in lactating and early weaned ewes in the 21-day group and 0.08 (1 of 13) and 0.36 (4 of 11) respectively in the 35-day group. The incidence of inadequate luteal function is therefore independent of the suckling stimulus and is higher in ewes induced to ovulate on Day 21 than Day 35 post partum during breeding and non-breeding seasons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2915356 TI - Effects of metalloendoprotease substrates on the human sperm acrosome reaction. AB - The substrates carbobenzyloxyserylleucylamide, carbobenzyloxyglycylleucylamide and carbobenzyloxyglycylphenylalanylamide were used as potential competitive inhibitors of endogenous metalloendoprotease activity. When the acrosome reaction was elicited by a potential physiological stimulus, human follicular fluid, each of the substrates (1-1.5 mM) inhibited exocytosis. Carbobenzyloxyserylleucylamide also inhibited the acrosome reaction when exocytosis was stimulated using the calcium ionophore ionomycin, but carbobenzyloxyglycylleucylamide was not inhibitory and carbobenzyloxyglycylphenylalanylamide actually enhanced exocytosis under these conditions. Experiments using the fluorescent indicator fura-2 revealed that the increase in intracellular, free calcium stimulated by follicular fluid in human spermatozoa was depressed by carbobenzyloxyglycylphenylalanylamide but not by carbobenzyloxyserylleucylamide. The peptide carbobenzyloxyglycylglycylamide, which is not a substrate for metalloendoproteases, had no effect on the acrosome reaction, whether stimulated by follicular fluid or ionomycin. While the results with carbobenzyloxyserylleucylamide suggest a possible involvement of a metalloendoprotease in the human sperm acrosome reaction, our other results demonstrate that these carbobenzyloxy peptides have complex effects on the process of exocytosis in human spermatozoa, and suggest caution in interpretation of data obtained using such peptides on intact cells. PMID- 2915357 TI - Ovarian interstitial tissue of the wood mouse, Apodemus sylvaticus. AB - The ovary of the wood mouse contains an unusually large amount of interstitial tissue which appears to develop from undifferentiated cells of the ovarian stroma and also by transformation of theca or granulosa cells of atretic follicles. The cells are characterized by the presence of smooth endoplasmic reticulum, rounded mitochondria with tubular cristae, and abundant, large (1.5 micron diameter) lipid droplets containing cholesterol and its esters. 3 beta-Hydroxysteroid dehydrogenase activity occurs in the interstitial cells. Their ultrastructural characteristics suggest that the cells are not very active, but their abundance and the considerable amount of steroid hormone precursor they contain may compensate for low secretory activity and they may be an important and (from a developmental viewpoint) early source of steroid hormone. PMID- 2915358 TI - Ability of progesterone to reverse anti-androgen (hydroxyflutamide)-induced interference with the preovulatory LH surge and ovulation in PMSG-primed immature rats. AB - In Exp. 1, PMSG was injected to 26-day-old prepubertal rats to induce ovulations. On Day 2 (2 days later, the equivalent of the day of pro-oestrus) they received at 08:00 h 5 mg hydroxyflutamide or vehicle and at 12:00 h 2 mg progesterone or testosterone or vehicle. Animals were killed at 18:00 h on Day 2 or at 09:00 h on Day 3. Progesterone but not testosterone restored the preovulatory LH surge and ovulation in hydroxyflutamide-treated rats. In Exp. 2, 2 mg progesterone or testosterone were injected between 10:30 and 11:00 h on Day 2, to advance the pro oestrous LH surge and ovulation in PMSG-primed prepubertal rats. Injection of hydroxyflutamide abolished the ability of progesterone to advance the LH surge or ovulation. Testosterone did not induce the advancement of LH surge or ovulation. In Exp. 3, ovariectomized prepubertal rats implanted with oestradiol-17 beta showed significantly (P less than 0.01) elevated serum LH concentrations at 18:00 h over those observed at 10:00 h. Progesterone injection to these animals further elevated the serum LH concentrations at 18:00 h, in a dose-dependent manner, with maximal values resulting from 1 mg progesterone. Hydroxyflutamide treatment significantly (P less than 0.003) reduced the serum LH values in rats receiving 0 1 mg progesterone but 2 mg progesterone were able to overcome this inhibition. It is concluded that progesterone but not testosterone can reverse the effects of hydroxyflutamide on the preovulatory LH surge and ovulation. It appears that hydroxyflutamide may interfere with progesterone action in induction of the LH surge, suggesting a hitherto undescribed anti-progestagenic action of hydroxyflutamide. PMID- 2915359 TI - Plasma concentrations of progesterone and testosterone in captive woolly opossums (Caluromys philander). AB - Plasma testosterone and progesterone concentrations were measured in captive woolly opossums, a didelphid marsupial originating from neotropical forests in French Guyana. Although not exposed to cyclic environmental conditions as in the field, both sexes exhibited spontaneous circannual changes in sexual hormones. Males showed synchronous variations in plasma testosterone characterized by significant elevated concentrations during April and September (8.6 +/- 1 ng/ml, N = 5) and lower levels from May to July (3.6 +/- 0.4 ng/ml). In females, synchronous periods of 2-3 successive oestrous cycles occurred. Between these periods, females remained acyclic. The oestrous cycle, determined by urogenital smears, lasted 28-45 days (n = 14) and included a 20-day spontaneous luteal phase in which progesterone concentrations reached 30-40 ng/ml plasma. Even though testosterone concentrations in paired males increased significantly in response to oestrous periods of the paired females, spontaneous circannual rhythms of sexual activity were not well synchronized between the sexes in captivity. When compared to field data, sexual activity of captive animals followed a pattern similar to that in wild animals, without any changes in males but with a delay of 3 months in females. PMID- 2915360 TI - Blood flow in the ovaries and ovarian follicles of Romanov and Prealpes-du-Sud ewes. AB - Radioactive microspheres (15 microns diameter) were used to measure capillary blood flow rates in the ovaries and ovarian follicles (Qf) in high fecund Romanov and low fecund Prealpes-du-Sud ewes at the preovulatory stage of the oestrous cycle. Additionally, assessments of the percentage of arterial blood passing through ovarian arterio-venous anastomoses were obtained. The mean +/- s.e.m. Qf per unit volume of theca [ml/min) x 10(4)/mm3) for non-atretic follicles in Romanov ewes was significantly greater (P less than 0.05) than that in Prealpes ewes (365.8 +/- 42.4, n = 19, compared with 241.3 +/- 30.1, n = 14). For each breed, the mean Qf value for non-atretic follicles was 8-10 times greater than that for atretic follicles. In Romanov ewes, total Qf [ml/min) x 10(4) and Qf per unit volume of theca was greatest in small-sized follicles (3.1-5.0 mm) while in Prealpes ewes, maximum flow was attained in larger-sized follicles (5.1-7.0 mm). The elevated Qf in small-sized follicles in Romanov ewes may be conducive to more follicles achieving maturation at a smaller diameter in this breed than occurs in the Prealpes ewes. The absence of flow through ovarian arterio-venous anastomoses in the Romanov, but not in the Prealpes, ewes suggests different mechanisms for controlling the distribution of the total ovarian blood supply in the 2 breeds. PMID- 2915361 TI - Influence of ejaculation frequency on semen characteristics in chimpanzees (Pan troglodytes). AB - Semen samples were obtained by masturbation from 6 chimpanzees and the spontaneously liquefied fraction and the remaining coagulum were studied separately. When semen was collected once or twice a week, large intra-individual variations were observed for all measures. The liquefied fraction represented 26.5 +/- 3.2% (weighted mean +/- s.d.) of the total ejaculate but contained 51.3 +/- 3.8% of all emitted spermatozoa. Fructose concentration was higher in the coagulum than in the liquefied fraction (29.3 +/- 3.0 mumol/ml vs 12.0 +/- 2.7 mumol/ml, P less than 0.001) whereas acid phosphatase was less concentrated in the coagulum than in the liquefied fraction (3.5 +/- 0.3 x 10(3) IU/ml vs 13.0 +/ 0.9 x 10(3) IU/ml, P less than 0.001). L-Carnitine and citrate concentrations did not differ between the two fractions of the ejaculate. When semen collection was repeated every hour for 5 h, the ejaculate volume increased from 2.6 +/- 0.7 to 4.7 +/- 0.6 ml (P less than 0.001), whereas total sperm count decreased from 1278 +/- 872 x 10(6) to 587 +/- 329 x 10(6) (P less than 0.05) between the 1st and the 6th ejaculate. In the spontaneously liquefied fraction, the sperm count decreased from 984 to 369 x 10(6). The 6 successive ejaculates gave a total of 20.2 +/- 7.6 ml and 4278 +/- 2884 x 10(6) spermatozoa. The increase of the ejaculate volume was essentially due to an increase of the volume of the coagulum which closely correlated with total amount of fructose (from seminal vesicles) (r = 0.913, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2915362 TI - Cell-specific variations and hormonal regulation of immunoreactive cytochrome P 450scc in the rat ovary. AB - Specific rabbit antibodies to the bovine cholesterol side-chain cleavage cytochrome P-450 (P-450scc) were used to cross-react with the enzyme in the rat ovary. The luteal cells of cyclic, pregnant, and pseudopregnant rats were immunostained. P-450scc was also expressed in the interstitial cells of prepubertal and cyclic adult rats, and in the thecal cells lining the preovulatory follicles. In cyclic females, RU 486 and oestradiol increased the intensity of P-450scc immunostaining. The granulosa cells of ovarian follicles whatever their stage of development, including preovulatory follicles, were not labelled, except after ovulation. The intensity of immunostaining of thecal and interstitial cells decreased during early pregnancy or pseudopregnancy, and disappeared after Day 9, whereas these cells were intensely labelled 24 h after parturition. The immunostaining of thecal and interstitial cells was again detected in 18-day pregnant rats, treated with the antiprogesterone RU 486. It is therefore concluded that both oestradiol and progesterone are involved in P 450scc regulation. PMID- 2915363 TI - Seasonal changes of testis volume and sperm quality in adult fallow deer (Dama dama) and their relationship to the antler cycle. AB - Four adult male fallow deer were investigated for 1-4 consecutive years to study the relationships between annual changes in testis volume, sperm quality and antler status. Testicular volume started to increase in July/August, peaked just before the rut, declined until December to 50% of maximum, persisted at this level up to February/March and reached minimal volume after antler casting in late April. There was no apparent age effect on the seasonality of testis size fluctuations. Velvet shedding and antler casting occurred at about 80% and 25%, respectively, of maximal testis volume. Spermatozoa had the same general appearance as those of related ruminants. Viable spermatozoa appeared between August and early May which corresponds almost exactly to the time when fallow deer are in hard antler. From September to March sperm quality would fulfil artificial insemination standards for cattle semen. In June and the first half of July 14 out of 15 ejaculates were devoid of any sperm cells. There were no indications of a secondary seasonal peak in values monitored. PMID- 2915364 TI - Development of preovulatory follicles expected to form short-lived corpora lutea in beef cows. AB - Oestrus, expected to be followed by a short luteal phase, was induced in post partum cows by weaning their calves at 35 days after parturition. Ovaries containing the first preovulatory follicles (Type F) formed after parturition were collected 3 h after the onset of oestrus. For comparison, preovulatory follicles (Type C) were collected 3 h after the onset of oestrus in normally cycling cows. The number of granulosa cells was determined and the concentrations of receptors for follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in granulosa cells and for LH in theca cells were measured. Concentrations of oestradiol-17 beta, testosterone, androstenedione and progesterone in follicular fluid were also measured. Type F follicles contained about twice the number of granulosa cells (based on DNA) as did Type C follicles (45.8 +/- 11.3 and 24.5 +/ 3.9 micrograms DNA/follicle, respectively; P less than 0.05) but these cells had fewer receptors for LH (0.13 +/- 0.02 vs 0.29 +/- 0.03 fmol/micrograms DNA; P less than 0.01) and FSH (0.61 +/- 0.08 vs 1.3 +/- 0.29 fmol/micrograms DNA; P less than 0.08) than did those from Type C follicles. Additionally, there were fewer receptors for LH in theca tissue from Type F than from Type C follicles (28.3 +/- 5.2 vs 51.3 +/- 6.1 fmol/follicle; P less than 0.01). Concentrations of oestradiol-17 beta (475.8 +/- 85.6 vs 112.9 +/- 40.0 ng/ml; P less than 0.01) and androstenedione (214.1 +/- 48.7 vs 24.7 +/- 7.7 ng/ml; P less than 0.01) in follicular fluid were higher in Type C than in Type F follicles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2915365 TI - Protection of mice by a pseudodiffuse strain of Staphylococcus aureus possessing polyvalent capsular type antigen. AB - Staphylococcus aureus strain MC31 showed pseudodiffuse growth in serum-soft agar and reacted with immune rabbit sera to strains Smith diffuse (capsular type A), NS58D (type B) and NS41D (type C) but not with strain NS68D (type D) in serum soft agar. Immunisation of mice with 300 micrograms of cell-surface polysaccharide extracted from strain MC31 protected against lethal infection by strain MC31 and the strains of capsular types A, B and C. Immune rabbit serum prepared against strain MC31 passively protected mice against challenge infection with the homologous strain, but approximately 30 times more anti-MC31 serum was required to protect against infection with the strains of capsular types A, B and C. Absorption of the passive protective activity of immune sera raised against the three capsular type strains required at least 10 times the quantity of MC31 cell-surface polysaccharide than the quantity of cell-surface polysaccharide from the homologous capsular strain. Electronmicrographs of strain MC31 treated with ferritin-labelled antisera to the three capsular strains showed only small amounts of ferritin granules around the cell wall. PMID- 2915367 TI - Establishment of an association between a virus and a human cancer. PMID- 2915366 TI - Comparison of preservation media and freezing conditions for storage of specimens of faeces. AB - To evaluate the long-term recoverability of bacterial enteropathogens, two freezing conditions (deep-freezing at -70 degrees C and liquid nitrogen) and three preservation media (Cary-Blair, Amies, and buffered glycerol-saline) were tested. These were compared with storage in containers with no preservation medium and refrigeration at 4 degrees C. At 4 degrees C, viability of organisms could not be consistently maintained beyond one month; Cary-Blair medium generally gave the best results and storage without preservation medium was the least efficient. Storage in liquid nitrogen and deep-freezing effectively preserved all organisms except Campylobacter jejuni for the entire period of study (12 months). There was no difference between the various preservation media, or between storage with or without medium. Storage in preservation medium was superior to storage without such supplement for C. jejuni. We conclude that most enteropathogens survive in faecal specimens for as long as 12 months when stored at very low temperatures (-70 degrees C) whether or not preservation media are used. PMID- 2915368 TI - Discover it today, tax it tomorrow: basic biomedical research spawns biotech industry. PMID- 2915369 TI - William Tipping leads American Cancer Society into 1990s. Interview by Adele Paroni. PMID- 2915370 TI - Covalent DNA damage in tissues of cigarette smokers as determined by 32P postlabeling assay. AB - Covalent DNA addition products (adducts) formed by the reaction of chemical carcinogens or their metabolites with DNA are critically involved in the initiation of chemical carcinogenesis and may serve as molecular markers and dosimeters for environmental carcinogen exposures. Using a highly sensitive 32P postlabeling assay for DNA adduct analysis, we studied DNA damage elicited by cigarette smoke in tissues of smokers. A multitude of characteristic smoking induced, presumably aromatic DNA adducts were found to occur in a dose- and time dependent manner in the lung, bronchus, and larynx of smokers with cancer of these organs and to decline only slowly after cessation of smoking. Low levels of adducts appeared to persist for up to 14 years in the lungs of exsmokers with high previous exposures. These results corroborate data of epidemiological studies showing that the lung cancer risk and mortality of smokers increase with the intensity and duration of smoking and decline only slowly after cessation of smoking. Tissue distribution studies in autopsy samples revealed the presence of smoking-associated DNA lesions also in the kidney, bladder, esophagus, heart, ascending aorta, and liver. The most extensive DNA damage was found in lung and heart, i.e., 1 aromatic adduct in about 10(7) DNA nucleotides. Our results suggest that cigarette smoking-induced DNA adduct formation is causally related to cancer in the target organs. PMID- 2915371 TI - Production and characterization of human glioma cell-derived monocyte chemotactic factor. AB - Since infiltration of monocytes into tumors may be mediated by tumor-derived chemoattractants, we characterized the monocyte-chemotactic activity (MCA) produced by glioma cell lines. The amount of MCA in the culture fluid of five lines tested differed by a factor of 25. U-105MG, the best producer, was selected for further study. After cells reached confluence and the medium was changed, MCA was detected by day 3 and remained at comparable levels on days 4 and 5. The molecular mass of MCA was approximately 17 kilodaltons, and the estimated isoelectric point ranged between pI 7 and pI 9. Because of the high constitutive production of MCA by U-105MG, sufficient material can be obtained for complete chemical characterization of this mediator of inflammation. PMID- 2915372 TI - Chromosomal characteristics and malignancy of urothelial cells from carcinogen treated rats. AB - Epithelial cells of bladders from male Fischer 344 rats that had been treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) or N-[4-(5-nitro-2-furyl)-2 thiazolyl]formamide (FANFT) were cultured and examined for chromosomal changes, anchorage independence in vitro, and transplantability in vivo. Numerical but not structural changes of chromosomes were significantly greater in the FANFT group than in the BBN group. Urothelial cell lines that demonstrated prolonged life span and loss of anchorage dependency were established from 14 of these rats, but only nine of them demonstrated tumorigenicity in the nude mouse model. Two of these transplantable cell lines and R4909, a transplantable bladder cell line derived from a 3-methylcholanthrene-treated rat, have normal chromosomes. The present study demonstrates a carcinogen-related chromosome change in the urothelial cells, but the relationship between malignancy and specific chromosomal changes is not clear. PMID- 2915373 TI - Loss of heterozygosity on chromosomes 1p and 11p in sporadic pheochromocytoma. AB - We used 29 polymorphic DNA markers to analyze tumor DNA samples from six patients with sporadic pheochromocytoma for possible loss of chromosomal heterozygosity; four had benign disease and two had malignant disease. Loss of heterozygosity was observed on four chromosomes: 1p (three of four patients), 2p (one of one), 5q (two of six), and 11p (three of five). Chromosomes 1p and 11p frequently had allelic deletions in these tumors, and these deletions may play an important role in the development of pheochromocytoma. PMID- 2915374 TI - Frequency of 13q abnormalities among 203 patients with retinoblastoma. AB - We studied peripheral blood lymphocyte karyotypes of 203 patients with retinoblastoma. Twelve (5.9%) had a constitutional chromosomal abnormality involving 13q, of whom six had unilateral and six had bilateral disease. Two patients had mosaic deletions, eight had nonmosaic deletions, one had a de novo translocation, and one had a 13q14 deletion and a de novo direct insertion (10;6). Of the total, 4.9% of unilateral and 7.5% of bilateral patients had 13q abnormalities. None of 19 familial retinoblastoma patients had a visible cytogenetic abnormality. The unilateral patients with 13q abnormalities represent prezygotically determined (potentially heritable) cases which would have been classified as postzygotic (sporadic) without cytogenetic analysis. The observed 1% frequency of mosaic deletions is lower than that previously reported. PMID- 2915375 TI - The ideal fetal head circumference calculation. AB - Various formulas have been employed to compute the circumference of an ellipse. These formulas can be separated into three groups: formulas for a circle, formulas for an incorrect ellipse, and a very complicated formula for a correct ellipse. The errors caused by the first two groups are termed systematic because they occur every time that one of these formulas is used. When measuring fetal head circumference, the errors increase as the fetal head is more ellipsoid, becoming more than 1% when the ratio of the biparietal to fronto-occipital diameter decreases to less than .70. Near term, when the fetal head is large, this could create an error in predicting gestational age of almost .8 weeks. The third group is associated with mathematical random errors because of the difficulty in using a cumbersome equation. All of these formulas and their shortcomings are analyzed. A calculation for the correct circumference of an ellipse is proposed using the simple formula for a circle times a correction factor. The correction factor depends solely on the ratio of the biparietal to fronto-occipital diameter. This formula should minimize random errors and eliminate systematic errors in the calculation of fetal head circumference and will permit a more accurate analysis of fetal age. PMID- 2915376 TI - Maternal transmission of retroviral disease and strategies for preventing infection of the neonate. AB - Moloney murine leukemia virus is efficiently transmitted from viremic mothers to offspring, primarily via virus-containing milk. To determine the level in the infectious process at which an antiviral agent can interfere most effectively with perinatal viral transmission, we examined the effect of the drug 3'-azido-3' deoxythymidine (AZT) on transmission of Moloney murine leukemia virus from viremic mothers to offspring. Although AZT treatment did not affect the titer of virus in milk, it did suppress the development of viremia in all offspring. AZT, however, did not prevent transmission of virus from viremic mothers to 25% of the offspring, but did lead to a marked reduction in virus load in these infected mice. These results provide evidence for effective antiretroviral therapy during gestation and in the perinatal period and are of potential significance for the management of maternal transmission of human retroviruses. PMID- 2915378 TI - Identification and nucleotide sequence of the glycoprotein gB gene of equine herpesvirus 4. AB - The nucleotide sequence of the glycoprotein gB gene of equine herpesvirus 4 (EHV 4) was determined. The gene was located within a BamHI genomic library by a combination of Southern and dot-blot hybridization with probes derived from the herpes simplex virus type 1 (HSV-1) gB DNA sequence. The predominant portion of the coding sequences was mapped to a 2.95-kilobase BamHI-EcoRI subfragment at the left-hand end of BamHI-C. Potential TATA box, CAT box, and mRNA start site sequences and the translational initiation codon were located in the BamHI M fragment of the virus, which is located immediately to the left of BamHI-C. A polyadenylation signal, AATAAA, occurs nine nucleotides past the chain termination codon. Translation of these sequences would give a 110-kilodalton protein possessing a 5' hydrophobic signal sequence, a hydrophilic surface domain containing 11 potential N-linked glycosylation sites, a hydrophobic transmembrane domain, and a 3' highly charged cytoplasmic domain. A potential internal proteolytic cleavage site, Arg-Arg/Ser, was identified at residues 459 to 461. Analysis of this protein revealed amino acid sequence homologies of 47% with HSV 1 gB, 54% with pseudorabies virus gpII, 51% with varicella-zoster virus gpII, 29% with human cytomegalovirus gB, and 30% with Epstein-Barr virus gB. Alignment of EHV-4 gB with HSV-1 (KOS) gB further revealed that four potential N-linked glycosylation sites and all 10 cysteine residues on the external surface of the molecules are perfectly conserved, suggesting that the proteins possess similar secondary and tertiary structures. Thus, we showed that EHV-4 gB is highly conserved with the gB and gpII glycoproteins of other herpesviruses, suggesting that this glycoprotein has a similar overall function in each virus. PMID- 2915377 TI - The second-largest subunit of the poxvirus RNA polymerase is similar to the corresponding subunits of procaryotic and eucaryotic RNA polymerases. AB - We have characterized the poxvirus gene encoding the second-largest subunit of the viral DNA-dependent RNA polymerase. This gene, designated rpo132, is located in the HindIII A fragment of the DNA of the Brighton Red strain of cowpox virus. A similar gene is located in the corresponding position in the HindIII A fragment of the DNA of the Western Reserve strain of vaccinia virus. The rpo132 gene is transcribed throughout the viral multiplication cycle. It has two transcriptional start sites; one is operative at late times only, and the other (80 base pairs downstream) is operative both at early times and at late times. Neither early nor late transcripts originating from the latter RNA start site contain long 5' terminal poly(A) sequences. The rpo132 gene has the capacity to encode primary gene products of two types. The RNA transcripts whose 5' ends correspond to the early RNA start site can encode a 133-kilodalton (kDa) protein. The RNA transcripts whose 5' ends correspond to the early RNA start site can encode a 132 kDa protein. Transcripts of the latter type are more abundant, suggesting that the 132-kDa protein is the major primary product of this gene. The predicted amino acid sequences of both gene products share extensive similarities with the amino acid sequences of the second-largest subunits of the following enzymes: the RNA polymerase of Escherichia coli, the RNA polymerase II of Saccharomyces cerevisiae, and the RNA polymerase II of Drosophila melanogaster. This result provides further evidence of relatedness between multisubunit DNA-dependent RNA polymerases. PMID- 2915379 TI - Structural defect linked to nonrandom mutations in the matrix gene of biken strain subacute sclerosing panencephalitis virus defined by cDNA cloning and expression of chimeric genes. AB - Biken strain, a nonproductive measles viruslike agent isolated from a subacute sclerosing panencephalitis (SSPE) patient, contains a posttranscriptional defect affecting matrix (M) protein. A putative M protein was translated in vitro with RNA from Biken strain-infected cells. A similar protein was detected in vivo by an antiserum against a peptide synthesized from the cloned M gene of Edmonston strain measles virus. By using a novel method, full-length cDNAs of the Biken M gene were selectively cloned. The cloned Biken M gene contained an open reading frame which encoded 8 extra carboxy-terminal amino acid residues and 20 amino acid substitutions predicted to affect both the hydrophobicity and secondary structure of the gene product. The cloned gene was expressed in vitro and in vivo into a 37,500 Mr protein electrophoretically and antigenically distinct from the M protein of Edmonston strain but identical to the M protein in Biken strain infected cells. Chimeric M proteins synthesized in vitro and in vivo showed that the mutations in the carboxy-proximal region altered the local antigenicity and those in the amino region affected the overall protein conformation. The protein expressed from the Biken M gene was unstable in vivo. Instability was attributed to multiple mutations in both the amino and carboxy regions. A surprising number of mutations in both the coding and noncoding regions of the Biken M gene were identical to those in an independently isolated SSPE virus strain with a similar defect. These results offer insights into the basis of the defect in Biken strain and pose intriguing questions about the evolutionary origins of SSPE viruses in general. PMID- 2915380 TI - Growth and survival of reovirus in intestinal tissue: role of the L2 and S1 genes. AB - Reovirus serotype 1 Lang can be recovered in high titer from the intestines of neonatal mice up to day 8 after peroral inoculation. By contrast, reovirus serotype 3 Dearing cannot be recovered from intestinal tissue past day 4 after peroral inoculation. This difference between the two reoviruses was mapped by using reassortants generated from nonmutagenized laboratory stocks. When the L2 and S1 genes of reovirus serotype 3 Dearing were present in reassortants, the reassortants behaved like serotype 3 Dearing in exhibiting a decreased capacity to be recovered from intestinal tissue. Likewise, viruses which contained the L2 and S2 genes from serotype 1 Lang exhibited an enhanced capacity to grow and survive, which is characteristic of serotype 1 Lang. Thus, the capacity of reovirus to survive in intestinal tissue was determined by the L2 and S1 genes. PMID- 2915381 TI - Purified influenza virus hemagglutinin and neuraminidase are equivalent in stimulation of antibody response but induce contrasting types of immunity to infection. AB - BALB/c mice immunized with graded doses of chromatographically purified hemagglutinin (HA) and neuraminidase (NA) antigens derived from A/Hong Kong/1/68 (H3N2) influenza virus demonstrated equivalent responses when HA-specific and NA specific serum antibodies were measured by enzyme-linked immunosorbent assays (ELISAs). Antibody responses measured by hemagglutination inhibition or neuraminidase inhibition titrations showed similar kinetic patterns, except for more rapid decline in hemagglutination inhibition antibody. Injection of mice with either purified HA or NA resulted in immunity manifested by reduction in pulmonary virus following challenge with virus containing homologous antigens. However, the nature of the immunity induced by the two antigens differed markedly. While HA immunization with all but the lowest doses of antigen prevented manifest infection, immunization with NA was infection-permissive at all antigen doses, although reduction in pulmonary virus was proportional to the amount of antigen administered. The immunizing but infection-permissive effect of NA immunization over a wide range of doses is in accord with results of earlier studies with mice in which single doses of NA and antigenically hybrid viruses were used. The demonstrable immunogenicity of highly purified NA as a single glycoprotein without adjuvant offers a novel infection-permissive approach with potentially low toxicity for human immunization against influenza virus. PMID- 2915382 TI - Characterization of a common high-affinity receptor for reovirus serotypes 1 and 3 on endothelial cells. AB - During viremia, viruses may be cleared from the bloodstream and taken up by specific organs. The uptake of virus from the bloodstream is dependent on the association of viral particles with endothelial cells that line the luminal surfaces of large and small blood vessels. To understand the nature of this interaction, we have studied the binding of reovirus serotypes 1 and 3 to these cells in vitro. Both serotypes of reovirus productively infected endothelial cells. By using [35S]methionine-biolabeled reovirus as a tracer ligand, we found that both viruses rapidly bind to endothelial cells and that equilibrium is reached after 4 h. The binding of the radiolabeled viruses was saturable and mediated by a homogeneous population of cellular receptors with very high affinity (Kd = 0.5 nM) for the virus ligands. Both serotypes bind to the same receptor, since the attachment of each radiolabeled serotype is inhibited by both the homologous and heterologous unlabeled virus. Exposure of labeled virus to monoclonal antibodies directed against the viral hemagglutinin (sigma 1 protein) inhibited binding, demonstrating that the attachment of reovirus to endothelial cells is mediated by the hemagglutinin for both serotypes. By using a novel ligand-blotting assay, the binding of both viruses to a 54,000-dalton protein could be demonstrated. The binding of each radiolabeled serotype to this protein was inhibited by the homologous and heterologous unlabeled serotype. By using cell fractionation after homogenization, we demonstrated that this 54-kilodalton protein is a membrane protein, in agreement with its proposed role as a cell surface receptor for reovirus serotypes 1 and 3. PMID- 2915385 TI - mRNA sequence and deduced amino acid sequence of the mumps virus small hydrophobic protein gene. AB - The mRNA of a putative small hydrophobic protein (SH) of mumps virus was identified in mumps virus-infected Vero cells, and its complete nucleotide sequence was determined by sequencing the genomic RNA and cDNA clones and partial sequencing of mRNA. The SH mRNA is 310 nucleotides long excluding the poly(A) and contains a single open reading frame encoding a protein of 57 amino acids with a calculated molecular weight of 6,719. The predicted protein is highly hydrophobic and contains a stretch of 25 hydrophobic amino acids near the amino terminus which could act as a membrane anchor region. There is no homology between the putative SH protein of mumps virus and the SH protein of simian virus 5, even though the SH genes are located in the same locus in the corresponding genome. One interesting observation is that the hydrophobic domain of simian virus 5 SH protein is at the carboxyl terminus, whereas that of mumps virus putative SH protein is near the amino terminus. PMID- 2915383 TI - Natural history of woodchuck hepatitis virus infections during the course of experimental viral infection: molecular virologic features of the liver and lymphoid tissues. AB - In this study, the kinetic patterns of woodchuck hepatitis virus (WHV) infection were monitored in the liver and the five primary components of the lymphoid system (peripheral blood lymphocytes, lymph nodes, bone marrow, spleen, and thymus). Groups of woodchucks experimentally infected with a standardized inoculum of WHV were sacrificed at different times over a 65-week period beginning in the preacute phase of viral infection and continuing to the period of serologic recovery or the establishment of chronic infections and subsequent hepatocellular carcinoma. Infection by WHV was not limited to the liver but involved the major components of the lymphoid system during all stages of virus infection. A complex series of kinetic patterns was observed for the appearance of WHV DNA in the different lymphoid compartments and the liver during the entire course of viral infection. A progressive evolution of different WHV genomic forms related to the replicative state of WHV was also observed. Lymphoid cells of the bone marrow were the first cells in which WHV DNA was detected, followed in order by the liver, the spleen, peripheral blood lymphocytes, lymph nodes, and finally the thymus. Several differences were observed in the cellular WHV DNA patterns between woodchucks that developed chronic WHV infections and those that serologically recovered from acute WHV infections. The observations compiled in this study indicate that the host lymphoid system is intimately involved in the natural history of hepadnavirus infections from the earliest stages of virus entry. PMID- 2915384 TI - Characterization of the major duck hepatitis B virus core particle protein. AB - The amino acid composition of the major duck hepatitis B virus (DHBV) core particle proteins was determined. The results of this analysis indicated that cores are composed of a single major protein that initiates translation from the second available AUG in the DHBV core gene. Proteins isolated from core particles purified from the cytoplasm of DHBV-infected duck hepatocytes exhibited heterogeneity in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, independent of the stage of viral DNA maturation. Incubation of native cores with alkaline phosphatase removed this heterogeneity, indicating that phosphorylation of external amino acids was responsible. Core protein isolated from mature DHBV purified from serum of infected animals did not display heterogeneity, suggesting a possible role for dephosphorylation in virus maturation. PMID- 2915386 TI - Self-ligating RNA sequences on the antigenome of human hepatitis delta virus. AB - A 179-base fragment of RNA from the 1,679-base antigenome of hepatitis delta virus can not only self-cleave but, when the ends of the resultant fragments are brought into apposition by base pairing to another RNA, also self-ligate. Thus, processing events needed for genome replication in vivo may be strictly RNA mediated. PMID- 2915387 TI - Genetic recombination of human immunodeficiency virus. AB - We investigated genetic recombination of the human immunodeficiency virus (HIV) in a tissue culture system. A clonal cell line expressing a single integrated HIV provirus with a termination codon affecting pol gene expression was transfected with different defective mutants derived from an infectious molecular clone of HIV. Replication-competent viral particles were recovered, passaged, and plaque purified. Restriction analyses of the proviral DNA corresponding to several of these viruses indicated that their emergence was the result of genetic recombination. PMID- 2915388 TI - raf/myc-infected erythroid cells are restricted in their ability to terminally differentiate. AB - A comparison was made of the in vitro erythroid colony-forming abilities of v-raf , v-myc-, and v-raf/v-myc-containing retroviruses. In methylcellulose, v-raf efficiently produced colonies of well-differentiated hemoglobin-synthesizing erythroid cells, whereas v-raf/v-myc-infected erythroid cells were inhibited from terminally differentiating but retained the ability to replicate extensively. In contrast, v-myc was unable to stimulate the formation of erythroid colonies. PMID- 2915390 TI - Bat rabies in Illinois: 1965 to 1986. AB - From 1968 to 1986, Illinois (USA) citizens and agencies submitted 4,272 bats to the Illinois Department of Public Health for rabies testing. Of this number, 6% tested positive, a rate comparable to similar studies from other parts of North America. Due to sampling biases, the true infection rate among bats in Illinois is probably lower than 6%. Additional analysis relied on a subsample (n = 2,433) of the specimens collected from 1965 to 1986. Prevalences were significantly different among years, but no linear trends were found over the study period. Evidence for a local outbreak of bat rabies was found. Prevalences for the species with sample sizes adequate for statistical analysis were, from high to low: hoary bat (Lasiurus cinereus), 11%; red bat (L. borealis), 5%; silver-haired bat (Lasionycteris noctivagans), 4%; little brown bat (Myotis lucifugus), 4%; big brown bat (Eptesicus fuscus), 3%; Keen's bat (Myotis keenii), 2%; and evening bat (Nycticeius humeralis), 2%. The higher prevalences found among the non-colonial species (hoary, red and silver-haired bats) were consistent with similar studies. Considerable annual variation in prevalences was found within species, and the prevalence rankings of the species varied over the study period. Prevalences were significantly higher in females (6%) than in males (4%) when species were pooled, but no significant differences between sexes were found within species. In contrast to the other species analyzed, all of which had sex ratios favoring females, the big brown bat sample had a large majority of males. Prevalences were significantly higher in adults (6%) than in juveniles (3%) when species were pooled. Within individual species, significant differences between age groups were found only for hoary and red bats; in two species, juveniles had higher prevalences. Above average prevalences were observed in May and August to November. Southern Illinois had the highest prevalences; prevalences were intermediate in the north and lowest in the central region. Overall, the patterns of rabies prevalence among bats submitted by the public in Illinois from 1965 to 1986 were similar to those reported from other parts of North America. PMID- 2915389 TI - Acceptance of simulated oral rabies vaccine baits by urban raccoons. AB - In summer 1986, a study was conducted to evaluate raccoon (Procyon lotor) acceptance of oral baits that could be used for rabies vaccination. One thousand wax-coated sponge bait cubes were filled with 5 mg of a seromarker (iophenoxic acid), placed in polyethylene bags, and hand-distributed in an 80 ha area within an urban National Park in Washington, D. C. (USA). After 3 wk, target and nontarget animals were trapped and blood samples collected to evaluate bait uptake. Thirty-three of 52 (63%) raccoons had elevated blood iodine levels indicating they had eaten at least one bait, 13 (25%) were negative, and six (12%) had marginal values. These results indicate that sponge baits hand-placed at a density of 12.4/ha can reach a significant proportion of an urban raccoon population. Implications for oral rabies vaccination of raccoons are discussed. PMID- 2915391 TI - An unusual clinical and pathological variant of malignant catarrhal fever in a white-tailed deer. AB - A captive male white-tailed deer (Odocoileus virginianus) developed an acute illness over a 3-day period characterized predominantly by neurological, ocular and respiratory signs which were accompanied by prominent gross lesions of multiple organ systems. Histologically, a proliferative vasculitis consisting primarily of lymphocytic-lymphoblastic cellular infiltration was found in ocular, oral, respiratory, cardiac and neural tissues. The extensive nature of these infiltrations resulted in grossly apparent nodular foci in the lung, lymphoid tissue and myocardium which were suggestive of a lymphoproliferative disorder. This is contrasted to the more necrotizing nature of the vasculitis observed in other reported cases of malignant catarrhal fever in white-tailed deer. Although virus isolation was not attempted, serologic findings of antibodies to malignant catarrhal fever virus detected by indirect immunofluorescence and virus neutralization supported a diagnosis of malignant catarrhal fever in this deer. PMID- 2915392 TI - Vertebral osteomyelitis and suspected diskospondylitis in an Atlantic bottlenose dolphin (Tursiops truncatus). AB - A 21-yr-old male Atlantic bottlenose dolphin (Tursiops truncatus) was performing at an aquatic park when it developed a soft tissue swelling anterior to the flukes. Subsequent radiographic evaluation revealed the animal to have vertebral osteomyelitis and suspected diskospondylitis. The case was successfully managed with long-term antibiotic therapy. PMID- 2915393 TI - Isolation of Aeromonas hydrophila from a captive caracal lynx (Felis caracal). AB - Aeromonas hydrophila was isolated from the internal organs of a captive caracal lynx (Felis caracal) which died of acute septicemia. Grossly, patchy areas of focal necrosis were found in the lungs, liver and kidney; there was ulceration in the stomach and intestines. Microscopically, lesions contained cellular debris, neutrophils, lymphocytes and gram-negative bacilli. This is the first report of isolation of Aeromonas hydrophila from a captive wild animal in Nigeria. PMID- 2915394 TI - Concurrent infection of a Patas monkey (Erythrocebus patas) by Citrobacter freundii and Trichuris trichiura. AB - Concurrent infection of Citrobacter freundii and Trichuris trichiura in a Patas monkey (Erythrocebus patas) is reported. A synergistic effect of both organisms contributing to host mortality in this case is suggested. PMID- 2915395 TI - Metacercariae of Diplostomum spathaceum in the eyes of fishes from Yellowstone Lake, Wyoming. AB - Fish were collected from Yellowstone Lake, Wyoming (USA). Metacercariae of Diplostomum spathaceum was found in the lens of 11 of 12 longnose suckers (Catostomus catostomus). The mean number of metacercariae per sucker was 59 and the average age of the fish was 11.6 yr. There was no correlation between age and intensity of parasites (r = 0.24). Of 10 cutthroat trout (Salmo clarki) examined, there were metacercariae present in six. The metacercariae were found outside of the lens tissue in the trout; they occurred in the vitreous humor and the retina. These may be a different species from those found in the suckers. PMID- 2915396 TI - Dirofilaria immitis in a raccoon (Procyon lotor). AB - A single juvenile male raccoon (Procyon lotor) was found naturally infected with Dirofilaria immitis. Two immature female worms were found in the heart of this raccoon at necropsy. Lesions attributable to the presence of these parasites were not found. Histopathologic examination of various tissues did not reveal any microfilariae. The raccoon may serve as an aberrant definitive host for this parasite, however, patent infections have not been reported. PMID- 2915397 TI - Acute arsenic toxication of a free-ranging white-tailed deer in New York. AB - An adult, female white-tailed deer (Odocoileus virginianus) died due to acute arsenic intoxication in an intensively managed northern hardwood forest in northern New York. We hypothesize that the deer licked trees injected with Silvisar 550, which contains monosodium methanearsonate. We believe this is the first report of death of a free-ranging white-tailed deer, due to ingestion of monosodium methanearsonate. PMID- 2915398 TI - Antagonism of xylazine hydrochloride sedation in raptors by yohimbine hydrochloride. AB - The mean time to initial reversal response (MTIRR) and the mean time to perching (MTP) were measured in 34 raptors sedated with xylazine hydrochloride with dosages ranging from 1.0 to 20 mg/kg intravenously (i.v.) and 2.5 to 20.0 mg/kg intramuscularly (i.m.). Yohimbine hydrochloride, given i.v. (0.2 mg/kg), 30 min after the injection of the xylazine, shortened the MTIRR and MTP compared to the controls. No adverse effects were noted due to the use of yohimbine. Yohimbine appeared to be a safe and effective antagonist for xylazine sedation in raptors. PMID- 2915399 TI - Effect of selected anthelmintics on three common helminths in the brown pelican (Pelecanus occidentalis). AB - The effect of selected anthelmintics (albendazole, fenbendazole, piperazine dihydrochloride and clorsulon) against three major helminths (Contracaecum multipapillatum, Mesostephanus appendiculatoides, and Phagicola longus) were studied in 29 brown pelicans (Pelecanus occidentalis). Albendazole and fenbendazole were highly effective against all three parasites. Clorsulon had moderate effect against M. appendiculatoides and poor effect against C. multipapillatum and P. longus. Piperazine dihydrochloride had no effect against these helminths. PMID- 2915400 TI - Cryptosporidium spp. in wild and captive reptiles. AB - Between 1986 and 1988, 528 reptiles originating from three continents were examined for Cryptosporidium spp. Fifteen specimens representing eight genera and 11 species were infected. Statistical evaluation of oocyst structure suggests that multiple species of Cryptosporidium may exist among the reptiles examined. PMID- 2915401 TI - Mycobacteriosis in yellow perch (Perca flavescens) from two lakes in Alberta. AB - Granulomatous skin lesions were identified in a population of yellow perch (Perca flavescens) from Sandy Lake (Alberta, Canada) in 1985. Severe granulomatous peritonitis and hepatitis was identified subsequently in a separate population of yellow perch from Wolf Lake (Alberta, Canada). Mycobacterium chelonae was isolated from affected fish in both epizootics. The source and route of infection were not determined in either case. The nature of the inflammatory reaction in both cases suggested a depressed immunity. PMID- 2915402 TI - Fusarium mycotoxins from peanuts suspected as a cause of sandhill crane mortality. AB - An estimated 9,500 sandhill cranes (Grus canadensis) died in Gaines County, Texas and Roosevelt County, New Mexico between 1982 and 1987. The predominant clinical sign observed in sick cranes was their inability to hold their heads erect, both while standing and flying. Multiple muscle hemorrhages and submandibular edema were the most common lesions seen at necropsy. Mycotoxins produced by Fusarium sp. growing during cold, wet weather on peanuts left in the field after harvest, the predominant foods of the dead cranes at the time of these mortality events, were identified as the most likely cause of this mortality. Rendering moldy peanuts inaccessible to the cranes by conventional tillage resulted in reduced crane mortality in these areas. PMID- 2915403 TI - Serologic evidence of Yersinia pestis infection in small mammals and bears from a temperate rainforest of north coastal California. AB - From 1983 to 1985, 463 serum samples from 11 species of mammals in Redwood National Park (RNP) (California, USA) were evaluated for antibodies to Yersinia pestis by the passive hemagglutination method. Yersinia pestis antibodies occurred in serum samples from 25 (36%) of 69 black bears (Ursus americanus), one (50%) of two raccoons (Procyon lotor), five (3%) of 170 dusky-footed woodrats (Neotoma fuscipes), and one (less than 1%) of 118 deer mice (Peromyscus maniculatus). Two hundred seventy-three flea pools, consisting of 14 species of fleas, were collected from small mammals and woodrat nest cups. Viable Y. pestis were not isolated from any of the flea pools. Significant between-year variations in the frequencies of seropositive bear or small mammal sera were not observed. A significantly higher frequency of plague antibodies was observed in bear sera taken during September collections. Frequencies of seropositive bear sera did not vary significantly by sex or age group of bears. Significant differences were not observed in the frequencies of seropositive small mammals by forest habitat type in which they were captured. This is the first report of Y. pestis infection in Redwood National Park, and the first detailed report of Y. pestis activity in a temperate rainforest. PMID- 2915404 TI - Periodontal disease in southern African bushpigs (Potamochoerus porcus) and warthogs (Phacochoerus aethiopicus). AB - Periodontal lesions were found in 14 of 100 bushpig (Potamochoerus porcus) skulls and nine of 103 warthog (Phacochoerus aethiopicus) skulls from southern Africa. The prevalence of periodontal disease showed a significant increase with age in the bushpig but not in the warthog skulls. All the lesions affected the cheek teeth, particularly the molars. The lower prevalence of lesions in older warthogs may be associated with their specialised molars and abrasive diet. PMID- 2915405 TI - Observations on the lungworm, Pneumostrongylus calcaratus, in impala (Aepyceros melampus) from Swaziland. AB - The lungworm, Pneumostrongylus calcaratus, was found in 85% (164 of 193) of impala (Aepyceros melampus) collected in Mlawula Nature Reserve in Swaziland. Infection was confirmed at 4.5 mo of age, and the prevalence increased to 100% at 11 mo, with a prevalence of 98% in animals greater than 1 yr of age. Pneumostrongylus calcaratus was usually found in firm, tangrey nodules along the lobar borders of the lungs, although an extensive granulomatous pneumonia with miliary caseous abscesses and calcified nodules was observed in some older animals. In the primary infection in lambs, adult parasites, larvae and eggs were observed in the alveoli and bronchioles within the nodule. There was peribronchial and perivascular mononuclear cuffing, with infiltration of mononuclear cells in the alveolar septum in the vicinity of worms. In lesions in older animals, there was local consolidation with macrophages and giant cells, and foci of parenchymal necrosis associated with degenerating eosinophils, which appeared to lead to the formation of eosinophilic granulomas. Resolving lesions caused interstitial fibrosis, with mineralized nodules. Pneumostrongylosis does not appear to pose a significant threat to the health of impala in Swaziland. PMID- 2915406 TI - A visceral mycosis in cultured masu salmon (Oncorhynchus masou) caused by a species of Ochroconis. AB - Ochronconis sp. infection was found in masu salmon (Oncorhynchus masou) with visceral mycosis in Japan. The external and internal clinical signs were reddening of the anal area, swelling of the abdomen due to accumulation of ascitic fluid in the abdominal cavity and extensive swelling of the posterior kidney. Many pale brown, septate hyphae were found in the kidney by direct microscopical examination; these were usually not found in the other organs of infected fish. Histopathological examination of the kidney revealed large granulomas with the fungal hyphae and giant cells. The isolated fungus was identified as a species of the genus Ochroconis and was compared with O. tshawytschae, a known fish pathogen. Based on morphological and growth characteristics, we believe that these cases resulted from infection with a different species. PMID- 2915407 TI - Physiological response of gray wolves to butorphanol-xylazine immobilization and antagonism by naloxone and yohimbine. AB - Captive gray wolves (Canis lupus) were immobilized (loss of consciousness) with 2.0 mg/kg xylazine hydrochloride (XYL) and 0.4 mg/kg butorphanol tartrate (BUT) administered intramuscularly. Induction time was 11.8 +/- 0.8 min (mean +/- SE). Immobilization resulted in bradycardia, respiratory depression, and normotension. Fifteen min after induction, six wolves were given either 0.05 mg/kg naloxone hydrochloride (NAL) and 0.125 or 0.250 mg/kg yohimbine hydrochloride (YOH), or an equal volume of saline (control) intravenously. Antagonism resulted in shortened recovery times compared to control animals (P less than 0.03); there was no difference in recovery times between the YOH doses (P greater than 0.05). Antagonism caused increases in heart rate (HR) and respiratory rate (RR), but no changes in MABP. Eight other wolves were similarly immobilized, but given only NAL. This resulted in partial antagonism with the animals appearing to be sedated with XYL only. Three wolves given only 0.4 mg/kg BUT assumed a state described as "apathetic sedation." Three other wolves sedated with only 2.0 mg/kg XYL showed a profound sedation characterized by recumbency, bradycardia and shallow, but regular, respiration. This study demonstrated that (1) BUT and XYL together, but not separately, can completely immobilize wolves, (2) this combination can be rapidly antagonized by NAL and YOH, and (3) there appeared to be no adverse cardiopulmonary reactions to any of the drugs used. PMID- 2915408 TI - HIV-1 infection among intravenous drug users in Manhattan, New York City, from 1977 through 1987. AB - Intravenous drug users are the second largest group to develop the acquired immunodeficiency syndrome, and they are the primary source for heterosexual and perinatal transmission in the United States and Europe. Understanding long-term trends in the spread of human immunodeficiency virus among intravenous drug users is critical to controlling the acquired immunodeficiency syndrome epidemic. Acquired immunodeficiency syndrome surveillance data and seroprevalence studies of drug treatment program entrants are used to trace seroprevalence trends among intravenous drug users in the borough of Manhattan. The virus entered this drug using group during the mid-1970s and spread rapidly in 1979 through 1983. From 1984 through 1987, the seroprevalence rate stabilized between 55% and 60%--well below hepatitis B seroprevalence rates. This relatively constant rate is attributed to new infections, new seronegative persons beginning drug injection, seropositive persons leaving drug injection, and increasing conscious risk reduction. PMID- 2915409 TI - Wide QRS tachycardia in the conscious adult. Ventricular tachycardia is the most frequent cause. AB - Hemodynamic stability during wide QRS tachycardia is commonly, albeit erroneously, taken as evidence for a supraventricular mechanism. To determine the magnitude for potential misdiagnosis in applying this notion clinically, we analyzed 20 consecutive cases of regular wide QRS tachycardia in conscious adult patients (mean age, 64 years). The most common heart disease was atherosclerotic (75%), with an associated history of remote myocardial infarction in 73% of the cases. Tachycardia was sustained for a mean of 4.8 hours prior to medical evaluation, with a mean rate of 186 beats per minute and mean systolic blood pressure of 111 mm Hg. A diagnosis of ventricular tachycardia (VT) was established in 17 cases (85%). In the patients with VT, atrioventricular dissociation was recognized on the 12-lead electrocardiogram in 38%, with Wellens' morphological features favoring the diagnosis in 73%. Following conversion to sinus rhythm, electrophysiological testing in 17 patients reproduced the clinical arrhythmia in 94% (with a replication rate of 100% in 15 patients with VT), with at least one additional unsuspected VT morphology induced in 53% of patients with VT. Thus, VT should be considered the most likely cause of regular wide QRS tachycardia in the conscious adult patient, especially with a history of remote myocardial infarction. Recognition of this simple principle and careful examination of the 12-lead electrocardiogram may help to prevent the misapplication of pharmacotherapy in the vast majority of these patients. PMID- 2915410 TI - Transdermal fentanyl for postoperative pain management. A double-blind placebo study. AB - A double-blind, placebo-controlled, randomized design was used to evaluate the safety and efficacy of transdermal fentanyl citrate for postoperative pain management in 42 healthy adult patients undergoing major shoulder surgery. Transdermal systems rated to deliver fentanyl citrate at a rate of 75 micrograms/h were applied to the skin immediately prior to surgery and worn for 24 hours. Patients in the active group required significantly less morphine than the placebo group during the 24-hour period that systems were in place (0.8 +/- 0.61 vs 1.3 +/- 0.64 mg/h) and for the first 12 hours after removal (0.3 +/- 0.36 vs 0.5 +/- 0.32 mg/h). The incidence of vomiting was more frequent in the active group than in the placebo group (73% vs 30%), and respiratory rate in the active group was lower than in the placebo group during the 13- to 24-hour interval of system application (14 +/- 3 vs 16 +/- 2 breaths per minute). Nevertheless, transdermal fentanyl appears to be safe and effective after orthopedic surgery in healthy adult patients. PMID- 2915411 TI - Will mountains trekkers have heart attacks? PMID- 2915412 TI - A piece of my mind. A woman's eyes. PMID- 2915413 TI - Campaign alerts physicians to identify, assist victims of domestic violence. PMID- 2915414 TI - Brain studies may alter long-held concepts about likely causes of some voice disorders. PMID- 2915415 TI - Six-year slowing noted in previously growing rate of US blood collections, transfusions. PMID- 2915416 TI - HIV-related disease in i.v. drug use. PMID- 2915417 TI - Leads from the MMWR. Education about adult domestic violence in U.S. and Canadian medical schools, 1987-88. PMID- 2915418 TI - Leads from the MMWR. Black/white comparisons of premature mortality for public health program planning--District of Columbia. PMID- 2915419 TI - A tough diagnosis in a neutropenic patient: it's cat-scratch disease. PMID- 2915420 TI - Human immunodeficiency virus-associated skin lesions. PMID- 2915421 TI - Pre-S2 and its antibody in fulminant type B hepatitis. PMID- 2915422 TI - Training the resident to meet the detail men. PMID- 2915423 TI - The suitability of HIV-positive individuals for marriage and pregnancy. PMID- 2915424 TI - Long-acting verapamil and heart failure. PMID- 2915425 TI - Waterborne Mycobacterium avium infection. PMID- 2915426 TI - Chest pain not always what it seems; panic disorder may be cause in some. PMID- 2915427 TI - Increased outdoor recreation, diminished ozone layer pose ultraviolet radiation threat to eye. PMID- 2915428 TI - Magnetic resonance spectroscopy may hold promise in studying metabolites, tissues. PMID- 2915429 TI - From the Assistant Secretary for Health. PMID- 2915430 TI - Leads from the MMWR. Measles--Los Angeles County, California, 1988. PMID- 2915431 TI - Respiratory syncytial virus pneumonia in a human immunodeficiency virus-infected man. PMID- 2915432 TI - The public cost of motorcycle trauma. PMID- 2915433 TI - Ethical problems in the medical office. PMID- 2915434 TI - The cost to patients of participating in clinical trials. PMID- 2915435 TI - The quality of care: how can it be assessed? PMID- 2915436 TI - The performance of a digital blood pressure monitoring device. PMID- 2915437 TI - Glucose control and the renal and retinal complications of insulin-dependent diabetes. AB - Two hundred thirty subjects with insulin-dependent diabetes were followed up longitudinally by measuring glycohemoglobin values to relate glucose control with renal and retinal complications. Subjects with long-term poor control (glycohemoglobin values greater than 1.5 times the upper limit of normal) had 3.6 times the prevalence of microalbuminuria and 2.5 times the prevalence of level 3 to 6 retinopathy than that found in subjects with long-term good control (glycohemoglobin values within 1.33 times the upper limit of normal). Variables related to kidney damage were glucose control and, to a lesser degree, duration of diabetes. Variables related to eye disease were, in descending order of significance, duration of diabetes, glucose control, and age. No subject whose mean glycohemoglobin value was consistently within 1.1 times the upper limit of normal had retinopathy or microalbuminuria. In contrast, when the mean glycohemoglobin value was more than 1.5 times the upper limit of normal, 24 (29%) of 82 subjects had microalbuminuria and 30 (37%) of 82 had level 3 to 6 retinopathy. PMID- 2915438 TI - Decreased selenium levels in acute myocardial infarction. AB - To study the association between selenium status and the risk of myocardial infarction, we compared plasma, erythrocyte, and toenail selenium levels and the activity of erythrocyte glutathione peroxidase among 84 patients with acute myocardial infarction and 84 population controls. Mean concentrations of all selenium measurements were lower in cases than controls. The differences were statistically significant, except for the plasma selenium level. A positive trend in the risk of acute myocardial infarction from high to low toenail selenium levels was observed, which persisted after adjustment for other risk factors for myocardial infarction. In contrast, erythrocyte glutathione peroxidase activity was significantly higher in cases than controls (31.3 +/- 8.4 U/g of hemoglobin and 28.0 +/- 8.1 U/g of hemoglobin, respectively). Because the toenail selenium level reflects blood levels up to one year before sampling, these findings suggest that a low selenium status was present before the infarction and, thus, may be of etiologic relevance. The higher glutathione peroxidase activity in the cases may be interpreted as a defense against increased oxidant stress either preceding or following the acute event. PMID- 2915439 TI - Contrasting effects of testosterone and stanozolol on serum lipoprotein levels. AB - Oral anabolic steroids produce striking reductions in serum concentrations of high-density lipoprotein (HDL) cholesterol. We hypothesized that this effect related to their route of administration and was unrelated to their androgenic potency. We administered oral stanozolol (6 mg/d) or supraphysiological doses of intramuscular testosterone enanthate (200 mg/wk) to 11 male weight lifters for six weeks in a crossover design. Stanozolol reduced HDL-cholesterol and the HDL2 subfraction by 33% and 71%, respectively. In contrast, testosterone decreased HDL cholesterol concentration by only 9% and the decrease was in the HDL3 subfraction. Apolipoprotein A-I level decreased 40% during stanozolol but only 8% during testosterone treatment. The low-density lipoprotein cholesterol concentration increased 29% with stanozolol and decreased 16% with testosterone treatment. Stanozolol, moreover, increased postheparin hepatic triglyceride lipase activity by 123%, whereas the maximum change during testosterone therapy (+25%) was not significant. Weight gain was similar with both drugs, but testosterone was more effective in suppressing gonadotropic hormones. We conclude that the undesirable lipoprotein effects of 17-alpha-alkylated steroids given orally are different from those of parenteral testosterone and that the latter may be preferable in many clinical situations. PMID- 2915440 TI - Studies in the distribution of body fat. III. Effects of cigarette smoking. AB - Cross-sectional associations between smoking habits, body mass index, and waist hip ratio (WHR) were examined in 1122 men aged 19 to 102 years. Weight and body mass index were significantly lower in cigarette smokers than in nonsmokers when age was taken into account. The WHR in smokers was significantly higher than in nonsmokers. A graded dose-response relationship was found between the number of cigarettes smoked and the WHR. Longitudinal associations between changes in smoking habits and changes in the WHR were examined during follow-up visits. In the period between these pairs of visits, weight increased when subjects quit smoking and decreased when they started smoking, as expected. The increase in WHR among those who quit smoking was, however, significantly less than the expected increase if smoking had continued. The WHR in those who started smoking actually increased despite their loss of weight. These paradoxical changes in WHR indicate that there are harmful effects of cigarette smoking on the pattern of distribution of body fat. These facts introduce still another reason to suggest that the decision to initiate or to continue smoking to control body weight is unwise. PMID- 2915441 TI - Randomized double-blind trial of intravenous prochlorperazine for the treatment of acute headache. AB - In a prospective, randomized, double-blind clinical trial, intravenous prochlorperazine edisylate (Compazine Edisylate) was compared with a placebo in the treatment of severe headaches. Eighty-two adult patients with vascular or tension-type headaches were identified at the time of presentation to one of three participating emergency departments. After the patient gave informed consent, a 2-mL intravenous injection of sterile saline solution or prochlorperazine edisylate (10 mg) was given to each patient at the time of randomization. The treatment groups were similar with regard to age, sex, and type and duration of headache. Within 60 minutes after injection, 74% (31/42) of those who received prochlorperazine had complete relief; 14% (6/42) of the patients had partial relief. Overall, there was complete or partial relief of pain in 88% (37/42) of the drug group and in 45% (18/40) of the placebo group. This difference was statistically significant using chi 2 analysis. Adverse effects were minimal; one patient experienced asymptomatic orthostatic hypotension. These results suggest that intravenous prochlorperazine is an effective treatment for patients with severe vascular or tension headaches who present to the emergency department. PMID- 2915442 TI - Fatal carbon monoxide poisoning at a motel. AB - One man died and four other persons required hospitalization following accidental exposure to carbon monoxide at a motel. In spite of prompt diagnosis of the index cases, a search for the source of exposure and for other possible victims was delayed more than ten hours. Subsequent investigation revealed that air conditioning units drew carbon monoxide from the gas heaters for the motel's indoor swimming pools into three adjacent guest rooms through structural defects in the walls. Emergency care providers must remember that in environmental exposures, other persons may continue to be at risk, and efforts must be made to identify them. PMID- 2915443 TI - The twilight zone: death on a Sunday morning. PMID- 2915444 TI - A piece of my mind. Liquid air. PMID- 2915445 TI - Sanitation, spirits, and medicine: health care in the African bush. PMID- 2915446 TI - As influenza season progresses, experts look ahead to 1990 season. PMID- 2915447 TI - Pacific basin may provide early flu warning. PMID- 2915448 TI - Vision-related problems may offer clues for earlier diagnosis of Alzheimer's disease. PMID- 2915449 TI - Mandatory reporting of HIV testing would deter men from being tested. PMID- 2915450 TI - No pretending not to know. PMID- 2915451 TI - ASA. PMID- 2915452 TI - Prophylactic lidocaine in acute MI. PMID- 2915453 TI - Who will die in the ICU? APACHE II, ROC curve analysis, and, of course, Cleone. PMID- 2915454 TI - Physicians and journalists. PMID- 2915455 TI - Prospective study of human immunodeficiency virus infection and pregnancy outcomes in intravenous drug users. AB - To determine the effects of human immunodeficiency virus (HIV) infection on pregnancy outcomes, we prospectively studied female intravenous drug users in a methadone program in New York City. Of 191 women with HIV status known prior to pregnancy, 17 (24%) of 70 seropositives and 26 (22%) of 121 seronegatives became pregnant during 28 months of follow-up. Including 54 additional women first tested for HIV antibody after becoming pregnant, 125 pregnancies were studied in 97 women (39 seropositive, 58 seronegative). None of the seropositive pregnant women had advanced HIV-related disease at entry, and only one developed symptomatic disease (oral candidiasis) during pregnancy. No differences were observed between groups in the frequency of spontaneous or elective abortion, ectopic pregnancy, preterm delivery, stillbirth, or low-birth-weight births. Among women giving birth to live infants, seropositives were more likely than seronegatives to be hospitalized for bacterial pneumonia during pregnancy and had an increased tendency for breech presentation, although these events were infrequent. There were otherwise no differences between groups in the occurrence of antenatal, intrapartum, or neonatal complications. Results suggest that asymptomatic HIV infection is not associated with a decreased pregnancy rate or an increased risk of adverse pregnancy outcomes in intravenous drug users, and that an acceleration in HIV-disease status during pregnancy is uncommon. PMID- 2915456 TI - Frequency and types of medical emergencies among commercial air travelers. AB - We performed a one-year prospective survey of emergency medical responses to travelers at an international airport to observe the frequency and type of emergencies experienced in flight and before and after travel. Emergency personnel evaluated a total of 1107 people; 754 (68%) were travelers, 232 (21%) were employees of the airport or airlines, and 118 (11%) were area residents. Of the 754 travelers, 190 (25%) experienced their problem during flight; the aircraft made an unscheduled landing for seven of these travelers. The frequency of in-flight emergencies was 1 per 753 inbound flights, or 1 per 39,600 inbound passengers. The most common emergency problems among all travelers were abdominal pain, chest pain, shortness of breath, syncope, and seizures; 25% of the emergencies were caused by minor trauma. The majority of emergencies among air travelers (75% [564/754]) happened on the ground within the air terminal. Most problems (84% [633/754]) were effectively handled by personnel trained as emergency medical technicians. The types of problems encountered suggest that the "doctors only" medical kit now required aboard US air carriers contains clinically useful items and should continue to be required on board. PMID- 2915457 TI - Benign familial hyperphosphatasemia. AB - Elevated alkaline phosphatase activity in serum suggests bone or liver disease or a neoplasm but can also indicate pregnancy or another benign condition. A family with benign hyperphosphatasemia was studied to elucidate the genetics and enzyme defect. Serum total alkaline phosphatase activity was greater than the population mean in all six family members, and more than 7 SDs above the mean in two of four offspring. Monoclonal antibodies to three alkaline phosphatase isoenzymes, intestinal, placental, and tissue nonspecific (liver/bone/kidney), demonstrated markedly increased intestinal alkaline phosphatase levels (29% to 44% of total) in all family members and significantly elevated liver/bone/kidney activity in the two offspring. Guanidine hydrochloride denaturation of the liver/bone/kidney component showed high alkaline phosphatase activity from liver in both siblings and from bone in one. The mode of inheritance in this family is obscure, but a complex regulation of the products of two different alkaline phosphatase genes seems likely. Steps toward diagnosis are suggested. Early recognition of this benign biochemical abnormality should help to avoid unnecessary diagnostic tests. PMID- 2915458 TI - Type D (delta) hepatitis. AB - In the ten years since the delta agent was discovered, major advances have been made in the understanding of its structure, genomic organization, replicative cycle, clinical course, and epidemiology. The recent breakthroughs in cloning of the HDV genome and development of animal models for study of this agent promise to transform these advances in knowledge to advances in means of prevention and therapy for this severe form of acute and chronic liver disease. PMID- 2915459 TI - HIV disease in reproductive age women: a problem of the present. PMID- 2915460 TI - The accidental tourist: medical emergencies in the air. PMID- 2915462 TI - Physicians as Good Samaritans: are they liable? PMID- 2915461 TI - A piece of my mind. Keola and the kahuna. PMID- 2915463 TI - Duty to warn. PMID- 2915464 TI - Should medical students treat HIV-infected patients? PMID- 2915465 TI - Caring for HIV-infected patients should not be required. PMID- 2915466 TI - [Epidemiology of cancer and its problems]. PMID- 2915467 TI - [A manual of the diagnosis and treatment of cancer]. PMID- 2915468 TI - [Diagnosis of head and neck neoplasms]. PMID- 2915469 TI - [Treatment of head and neck neoplasms]. PMID- 2915470 TI - [Immunologic diagnosis of cancer--tumor markers]. PMID- 2915471 TI - [Mediastinal tumors]. PMID- 2915472 TI - [Treatment of breast cancer]. PMID- 2915473 TI - [Treatment of thyroid cancer]. PMID- 2915474 TI - [Parathyroid carcinoma]. PMID- 2915475 TI - [Treatment of esophageal cancer]. PMID- 2915476 TI - [Treatment of stomach cancer]. PMID- 2915477 TI - [Tumors of the small intestine]. PMID- 2915478 TI - [Diagnosis of colonic cancer]. PMID- 2915479 TI - [Treatment of colonic cancer]. PMID- 2915480 TI - [Diagnosis of rectal and anal cancer]. PMID- 2915481 TI - [Treatment of rectal and anal cancer]. PMID- 2915482 TI - [Treatment of liver cancer]. PMID- 2915483 TI - [Treatment of biliary tract cancer]. PMID- 2915484 TI - [Treatment of pancreatic cancer]. PMID- 2915485 TI - [Hyperthermic therapy of cancer]. PMID- 2915486 TI - [Diagnosis of carcinoma of the uterine cervix]. PMID- 2915487 TI - [Treatment of carcinoma of the uterine cervix]. PMID- 2915488 TI - [Diagnosis of uterine cancer]. PMID- 2915489 TI - [Treatment of uterine cancer]. PMID- 2915490 TI - [Tumors of the vagina and vulva]. PMID- 2915491 TI - [Laser treatment of cancer]. PMID- 2915492 TI - [Bladder tumors (transitional cell carcinoma)]. PMID- 2915493 TI - [Testicular tumors]. PMID- 2915494 TI - [Cancer of the penis]. PMID- 2915495 TI - [Tumor of the adrenal gland]. PMID- 2915496 TI - [Diagnosis of osteogenic sarcoma]. PMID- 2915497 TI - [Treatment of osteogenic sarcoma]. PMID- 2915498 TI - [Malignant melanoma]. PMID- 2915499 TI - [Childhood leukemia]. PMID- 2915500 TI - [Diagnosis of adult leukemia]. PMID- 2915501 TI - [Diagnosis of brain tumors]. PMID- 2915502 TI - [Diagnosis of malignant lymphoma]. PMID- 2915503 TI - [Carcinoids]. PMID- 2915504 TI - [Hypercalcemia]. PMID- 2915505 TI - [Leukemoid reactions]. PMID- 2915506 TI - [Cancer and immunodeficiency]. PMID- 2915507 TI - [Cancer and blood coagulation disorders]. PMID- 2915508 TI - [Multiple cancer syndromes]. PMID- 2915509 TI - [Second cancer following radiation treatment]. PMID- 2915510 TI - [Second malignancies and cancer chemotherapy]. PMID- 2915511 TI - [Lists of antineoplastic agents]. PMID- 2915512 TI - [Spinal cord tumors]. PMID- 2915513 TI - Food restriction retards body growth and prevents end-stage renal pathology in remnant kidneys of rats regardless of protein intake. AB - The objectives of this study were to evaluate the effects of food restriction (without protein or phosphorus restriction) and protein restriction (without the restriction of other nutrients or calories) on the outcome of the remnant kidney model of chronic renal failure in rats. After 5/6 nephrectomy, rats were assigned to one of the following dietary groups: group I (control-ad libitum) consumed a 21% casein diet ad libitum; group II (food restriction with protein restriction) consumed 36% less calories, protein and minerals than group I; group III (food restriction without protein restriction) consumed 36% less calories and minerals than group I, but equivalent amounts of protein; group IV (protein restriction) consumed 38% less protein than group I, but equivalent amounts of calories and minerals; group V (NaCl restriction) consumed 40% less sodium chloride than group I, but equivalent amounts of all other nutrients. All groups consumed equivalent amounts of calcium, phosphorus and vitamins. Groups II and III experienced retardation of growth in comparison to groups I, IV and V. The food-restricted groups II and III, but not groups IV and V, had less proteinuria than group I 20 weeks postablation. By 21 weeks postablation, the kidneys from group I showed severe parenchymal damage, characteristic of end-stage renal pathology. These changes were prevented in the food-restricted groups II and III, but not in groups IV and V. The percentage of glomeruli with severe structural damage was less in groups II (27.3 +/- 8.8) and III (26.9 +/- 7.5) compared with group I (72.4 +/- 7.8). In contrast, the corresponding values in groups IV and V were not significantly different from group I. Interstitial volume (the percentage of tubulointerstitium which is interstitium) which was proportional to the severity of tubular damage was significantly lower in groups II (25.1 +/- 4.5) and III (20.4 +/- 2.8) when compared with groups I (48.1 +/- 3.0), IV (44.4 +/- 6.6), or V (41.9 +/- 4.2). An interstitial volume less than 30 correlated with well preserved renal histology, whereas a value greater than 40 was indicative of end stage renal pathology. These results indicate that the restriction of carbohydrate, fat, and minerals (except for calcium and phosphorus) retarded growth and prevented the development of end-stage renal pathology in the remnant kidney model of chronic renal failure in rats, regardless of whether protein was restricted or not.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2915514 TI - Age-related nephropathy and proteinuria in rats with intact kidneys exposed to diets with different protein content. AB - Tubulointerstitial damage and glomerular sclerosis are findings commonly observed in the experimental models of adriamycin and puromycin aminonucleoside nephrosis. It has been suggested that in such models proteinuria might be an important mediator of tubulo-interstitial damage which in turn may determine the progression of the disease favoring the development of glomerulosclerosis. The objective of the present investigation was to establish the temporal relationship between proteinuria, tubulo-interstitial damage and glomerulosclerosis in aging rats with intact kidneys exposed to diets with different protein content. There were six groups of rats studied. Animals of groups 1, 5, and 6 (N = 10) were fed diets containing 20, 35, and 6% protein, respectively, for 20 months and sacrificed at the end of the experimental period. Rats in groups 3 and 4 (N = 6) exhibited marked and mild proteinuria, respectively, after 14 months of maintenance on standard diet, and followed for two additional months after the onset of proteinuria with the aim of evaluating the pattern of renal damage after a relatively short period of proteinuria. Rats in group 2 (N = 10) were fed standard diet and sacrificed before (5 months) and at the onset of proteinuria (10 months). Protein excretion and plasma creatinine were measured for each animal every month. Pathologic examination was performed by light and electron microscopy. At the onset of proteinuria neither renal structural nor functional abnormalities were detected. After 20 months, rats fed standard diet developed tubulo-interstitial damage (score: 1.29 +/- 1.05) and focal glomerular sclerosis (percentage of glomeruli with focal segmental glomerular sclerosis: 16.70 +/- 16.40). A significant correlation was found between the degree of tubulo interstitial damage and the percentage of glomeruli with focal glomerular sclerosis (r = 0.99, p less than 0.01). Development of tubulo-interstitial damage and focal glomerular sclerosis were correlated with heavy and sustained proteinuria. The high protein diet significantly worsened proteinuria (at month 20: 247.08 +/- 101.73 mg/day), tubulo-interstitial changes (score: 1.99 +/- 0.70), focal glomerular sclerosis (percentage of glomeruli with focal segmental glomerular sclerosis: 21.50 +/- 9.44) and was associated with deteriorating renal function (at month 20, plasma creatinine: 1.20 +/- 0.50 mg/dl).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2915515 TI - Glomerular hypertrophy and epithelial cell injury modulate progressive glomerulosclerosis in the rat. AB - The effects of glomerular size and visceral epithelial cell integrity upon the development of progressive glomerulosclerosis was studied by superimposing renal ablation on adriamycin-induced nephropathy in rats. Adriamycin alone caused focal epithelial cell injury and proteinuria but minimal segmental glomerulosclerosis. In normal rats, renal ablation was accompanied by mild progressive proteinuria and glomerulosclerosis. However, renal ablation in rats with adriamycin nephropathy caused a dramatic increase in proteinuria and a disproportionately high frequency of segmental glomerulosclerosis. Accelerated glomerular injury after renal ablation in adriamycin-treated rats was associated with substantial glomerular hypertrophy with near doubling of the tuft volume. Morphometric and autoradiographic studies showed that compensatory glomerular hypertrophy occurs without a proportional increase in the number of visceral epithelial cells, leading to a substantial reduction in the density of these cells within the capillary tuft. The severity of segmental glomerulosclerosis showed a significant correlation with the glomerular volume and the reciprocal of the visceral epithelial cell density. Ultrastructural observations indicate that epithelial defects with detachment of the cell processes from the underlying basement membrane are almost invariably seen in areas of segmental glomerulosclerosis with hyalinosis. These findings suggest that the process of progressive glomerulosclerosis is, to a great extent, contingent upon the development of epithelial cell defects, that result from direct injury or from a reduction in the cell density after inordinate compensatory glomerular hypertrophy. PMID- 2915516 TI - Morphologic heterogeneity along the rat inner medullary collecting duct. AB - The qualitative and quantitative morphologic features of the cells lining the inner medullary collecting duct (IMCD) in the outer (IMCD1), middle (IMCD2) and inner (IMCD3) segments were investigated. Kidneys of male rats were fixed by in vivo vascular perfusion with glutaraldehyde and processed for light microscopy and scanning and transmission electron microscopy. The IMCD1 consisted of both principal cells and intercalated cells similar to those present in the outer medullary collecting duct. The principal cells were covered with small microvilli and a single cilium. Most of the IMCD2 and the entire IMCD3 contained one cell type (IMCD cell). When compared with the principal cells, the IMCD cells were taller, had fewer basal infoldings and a lighter staining cytoplasm containing numerous free ribosomes and small electron-dense cytoplasmic bodies in the basal region. The luminal surface was covered with prominent microvilli, but had no cilia. Morphometric analysis demonstrated that the surface density of apical and basal plasma membranes decreased from IMCD1 to IMCD3. However, because of an overall increase in tubule volume from IMCD1 to IMCD3, there were no significant differences in the absolute area of apical or basal membranes between the three segments. In contrast, the absolute area of lateral membranes increased significantly from IMCD1 to IMCD3. This study demonstrates that the IMCD1 consists of principal cells and intercalated cells similar to those in the outer medullary collecting duct, whereas the cells in most of the IMCD2 and the entire IMCD3 appear to represent a distinct and separate cell type which we choose to call the IMCD cell. Thus, both morphologic and functional heterogeneity appear to exist along the IMCD. PMID- 2915517 TI - Glomerular capillary morphology in normal humans. AB - Knowledge of quantitative glomerular structure in normal man is limited. At the time of renal transplantation, 28 living-related normal kidney donors had renal biopsies performed. Tissue was processed for light and electron microscopy using standard techniques. Standard stereologic techniques were used to determine mean glomerular volume, capillary length density, fractional volumes of mesangium and capillary lumen, surface densities of the peripheral capillary, mesangial epithelium interface, and the lumenal-mesangial interface. Volume of total mesangium/glomerulus, capillary lumenal volume/glomerulus, peripheral capillary filtration surface/glomerulus, capillary mesangial-epithelial surface/glomerulus, capillary lumenal-mesangial surface/glomerulus, capillary length/glomerulus, and average capillary diameter were calculated. There were no significant differences between males and females in any structural parameter. There were no significant correlations between age or body surface area and any structural parameter. In comparison with these normal values, previously reported diabetic patients with clinical nephropathy demonstrate markedly expanded mesangial volume/glomerulus and a diminished filtration surface/glomerulus. The availability of these normal values will allow comparison with functional data in normal humans and greater understanding of human glomerular disease. PMID- 2915518 TI - Rapid barrier restitution in an in vitro model of intestinal epithelial injury. AB - Mild forms of intestinal epithelial injury commonly occur in many disease states. In order to study how such epithelial "wounds" heal, we have developed a highly reproducible in vitro model of intestinal epithelial injury. Guinea pig ileal mucosal sheets were mounted in Ussing chambers and the mucosal surfaces were exposed to 0.06% Triton-X 100 for 5 minutes. This resulted in denudation of the epithelium at the tips of 86% of villi. As a result of this injury, resistance to passive ion flow decreased significantly (56.5 +/- 1.3 versus 38.4 +/- 2.3 ohm.cm2 for control and injury, respectively, p less than 0.01), as did transepithelial potential difference (-11.9 +/- 0.7 versus -4.3 +/- 0.4 mV for control versus injury respectively, p less than 0.01). In parallel, transepithelial fluxes of the extracellular space markers mannitol and inulin increased 3- to 5-fold immediately after injury. Two hours after injury, villus tips were again confluently covered by columnar absorptive cells, a time course of healing too fast to be accounted for by enhanced cell proliferation. Analysis of the structural events occurring during recovery showed that absorptive cells shouldering the foci of denudation rapidly changed shape after injury: they became flattened and sent cell projections over the denuded basement membrane. By 60 minutes after injury, cells from opposite shoulders of the denudation abutted, thus resealing the defect. Paralleling these structural changes, transepithelial resistance, potential difference, and mannitol and inulin fluxes returned toward control values. These data show that focal epithelial discontinuities in the small intestine may be rapidly resealed. Such reparative processes may substantially limit the deleterious physiologic impact of superficial forms of intestinal injury. PMID- 2915519 TI - Histologic and scanning electron microscopic observations of intrahepatic peribiliary glands in normal human livers. AB - The three-dimensional configuration of the intrahepatic peribiliary glandular system was examined in normal autopsied livers by scanning electron microscopic observations of the intrahepatic biliary tract casts. Biliary tract casts were made by injection of resin into the biliary tree and subsequent corrosion of the hepatic parenchyma. There were many projections on the surface of the biliary casts and they could be morphologically classified into pouchlike and treelike projections. These projections tended to be arranged on opposite sides of the biliary casts. The treelike projections from the large bile ducts at the bifurcation frequently anastomosed each other. By comparing the findings of biliary casts with histologic findings as well as the measuring of these projections and thickness of bile duct wall, it was suggested that the treelike projections correspond to the extramural peribiliary glands and the pouchlike ones to the intramural ones, both of which are normally present around the intrahepatic biliary tree. Thus, it was suggested stereologically in this study that substance(s) produced in the intrahepatic peribiliary glands may be secreted into the bile ductal lumen and thereby participate in the modification of bile composition. PMID- 2915520 TI - The concurrent validity of the Minnesota Child Development Inventory as a measure of young children's language development. AB - The extent to which the Minnesota Child Development Inventory (MCDI), could be used to estimate levels of language development in 2-year-old children was examined. Fifty-seven children between 23 and 28 months were given the Sequenced Inventory of Communication Development (SICD), and at the same time a parent completed the MCDI. In addition the mean length of utterance (MLU) was obtained for each child from a spontaneous speech sample. The MCDI Expressive Language scale was found to be a strong predictor of both the SICD Expressive scale and MLU. The MCDI Comprehension-Conceptual scale, presumably a receptive language measure, was moderately correlated with the SICD Receptive scale; however, it was also strongly correlated with the expressive measures. These results demonstrated that the Expressive Language scale of the MCDI was a valid predictor of expressive language for 2-year-old children. The MCDI Comprehension-Conceptual scale appeared to assess both receptive and expressive language, thus complicating its interpretation. PMID- 2915521 TI - Nonfluencies of preschool stutterers and conversational partners: observing reciprocal relationships. AB - Nonfluencies produced by 12 stutterers (2-6 years old) interacting in three dyadic sessions were analyzed. A stutterer played with his own mother, own father, and a familiar peer for 10 min. Results indicated that the total frequencies and types of nonfluency observed were very similar in each of the play situations. Although stutterers exhibited more part-word repetitions and prolongations than any other type of nonfluency, they did not differ in the amount and type of nonfluency when talking to their three conversational partners. Because children have more breakdowns in fluency than adults, it was not surprising that peers were more nonfluent when talking to the stutterer than were the parents. Peers used significantly more part- and whole-word repetitions, tense pauses, and interjections than the parents did. The nonfluency levels of the parent partners were quite similar when talking to the stutterers. PMID- 2915522 TI - Speech and language in maltreated children: response to McCauley and Swisher (1987) PMID- 2915523 TI - Word recognition functions for the CID W-22 test in multitalker noise for normally hearing and hearing-impaired subjects. AB - Word recognition functions for Auditec recordings of the CID W-22 stimuli in multitalker noise were obtained using subjects with normal hearing and with mild to-moderate sensorineural hearing loss. In the first experiment, word recognition functions were generated by varying the signal-to-noise ratio (S/N); whereas in the second experiment, a constant S/N was used and stimulus intensity was varied. The split-half reliability of word recognition scores for the normal-hearing and hearing-impaired groups revealed variability that agreed closely with predictions based on the simple binomial distribution. Therefore, the binomial model appears appropriate for estimating the variability of word recognition scores whether they are obtained in quiet or in a competing background noise. The reliability for threshold (50% point) revealed good stability. The slope of the recognition function was steeper for normal listeners than for the hearing-impaired subjects. Word recognition testing in noise can provide insight into the problems imposed by hearing loss, particularly when evaluating patients with mild hearing loss who exhibit no difficulties with conventional tests. Clinicians should employ a sufficient number of stimuli so that the test is adequately sensitive to differences among listening conditions. PMID- 2915524 TI - Speech spectrum considerations and speech intelligibility predictions in hearing aid evaluations. AB - This report deals with the issue of the amplified and unamplified speech spectra as they relate to the residual auditory range. The methods for predicting intelligibility of both amplified and unamplified speech are discussed. Based on Pavlovic (1987) an articulation index-based procedure applicable to clinical data is derived (A1). A simplified version (A0) is also proposed. PMID- 2915525 TI - Using a barrier game format to improve children's referential communication skills. AB - The effectiveness of training referential communication skills with learning disabled (LD) students was investigated. Forty-two upper elementary-aged children were divided equally into three groups: (a) an LD training group, (b) an LD control group, and (c) a normally achieving training group. The normal group was included as a check on training procedures. All subjects were administered pretests. The measures were a listening task and two speaking tasks. The two training groups were trained in dyads on a referential communication task. Posttests were administered 1 week after training. Results indicated that on the listening task the groups were not significantly different. On both speaking measures, the LD trained group achieved significantly higher scores than did the LD control group. The LD and normally achieving training groups were not significantly different. Follow-up testing 7 months later indicated that significant differences remained between the two LD groups on one of the speaking measures. It is concluded that LD students can benefit from training on referential communication tasks. PMID- 2915526 TI - Phonologic abilities of a preschool child with Prader-Willi syndrome. AB - The case study follows the development of phonologic abilities in a child with Prader-Willi syndrome from age 2:7 to 6:1 during a period in which she was enrolled in language and phonologic remediation. Changes in her phonetic inventory, in the set of phonemes used correctly, and in phonologic processes are described. Although her phonologic system appeared to parallel those of normally developing children in many ways, some unusual sounds and patterns of usage were also seen. Because the effect of the treatment program on the development of her phonologic system cannot be adequately determined, clinicians should use caution when generalizing these results to other children with this syndrome. PMID- 2915527 TI - Effects of imitation on language comprehension and transfer to production in children with mental retardation. AB - This study investigated the effects of verbal imitation on the comprehension of novel object-location responses and subsequent transfer of these responses to production. A matrix training procedure was used to teach 2 children with moderate mental retardation syntactic rules for combining known and unknown words into two-word utterances. An alternating treatments design was used with two conditions: receptive teaching with imitation of the target phrase and no imitation of the phrase. Findings suggested that the use of imitation facilitated both generalized receptive learning and transfer to production in both subjects. PMID- 2915528 TI - Surface EMG and related measures in normal and vocally hyperfunctional speakers. AB - Surface electromyographic (EMG) signals were detected from the laryngeal area of 7 normal and 7 vocally hyperfunctional speakers during rest, two resisted-force maneuvers, vowel production, and connected speech. Vowel fundamental frequency, absolute and relative period perturbation, laryngeal-palpation ratings, and harshness ratings were acquired as well. The two groups differed significantly on all EMG measures except those associated with the resisted-force maneuvers, the vowel EMG-to-rest EMG ratio, and the speech EMG-to-rest EMG ratio. Moderately high correlations were evident between selected clinical measures and speech EMG values. PMID- 2915530 TI - Maximal opposition approach to phonological treatment. AB - The purpose of this paper was to evaluate a phonological treatment program of maximal rather than minimal feature contrasts by charting the course of learning in a child displaying a systematic error pattern involving the nonoccurrence of word-initial consonants. Generalization data indicated that the child learned 16 word-initial consonants following treatment of only three sets of maximal opposition contrasts. Overgeneralization data indicated that the child restructured his phonological system based on a larger concept of "word initialness." Basic components of and differences between various forms of contrast treatment are discussed. PMID- 2915529 TI - Differentiating Alzheimer's patients from the normal elderly and stroke patients with aphasia. AB - The performance of individuals with mild and moderate Alzheimer's disease (AD), normal age-matched elderly individuals, and stroke patients with fluent and nonfluent aphasia were compared on a group of neuropsychological tasks. The unique performance profiles associated with each subject group are discussed, and the best tasks for intergroup differentiation specified. Whereas the tasks employed were efficacious for discriminating early- and middle-stage AD patients from normal subjects and aphasic stroke patients, and early- from middle-stage AD patients, they were not efficacious for subtyping aphasia patients according to fluency. Generally, memory measures were best for intergroup differentiation. PMID- 2915531 TI - Recovery from OME-related phonologic delay following tube placement. AB - Subjects with documented histories of frequent or persistent otitis media with effusion (OME) who were judged to be below age level phonologically prior to placement of pressure equalization (PE) tubes were reassessed at 4-month intervals. Group A (n = 22) subjects caught up with their peers by the age of 4 years; Group B (n = 14) subjects' progress was delayed and phonologic intervention was advised. At initial testing the two groups were found to differ significantly in scores on postvocalic singleton obstruent omission, velar deviation, and stridency deletion. Elapsed time between initial diagnosis of OME and beginning of the first remission of 6 months or more also differed significantly, as did scores on the first phonologic reassessment. Subject scores on initial phonologic adequacy, retest adequacy, and elapsed time from diagnosis to remission appropriately classified all but 2 subjects by group. A formula is provided that appears to make early prediction of eventual need for phonologic intervention a practical possibility. PMID- 2915532 TI - The NIH clinician-investigator award: how to write a training grant application. PMID- 2915533 TI - Increased plasma oncotic pressure inhibits pulmonary fluid transport when pulmonary pressures are elevated. AB - Hydrostatic and oncotic pressures are the primary determinants of fluid movement across the pulmonary vascular membrane. The precise role of oncotic pressure in regulating transvascular fluid exchange especially when hydrostatic pressure is high is not known. Awake, adult sheep were instrumented for pressure monitoring and the collection of pulmonary lymph. A left atrial (LA) balloon catheter was utilized to control LA pressure. Statistically significant increases in lymph protein flux were seen with infusion of saline and elevated pulmonary microvascular pressure (Pmv) over elevated Pmv alone (15.3 +/- 1.23 versus 11.2 +/- 1.09 mg/min) concomitant with a decrease in plasma colloid oncotic pressure (COP) (14.9 +/- 0.5 versus 16.9 +/- 0.5 mm/Hg). The protein flux seen with elevated Pmv and saline infusion was blunted when plasma was infused (13.8 +/- 1.58 mg/min) and the plasma COP augmented (18.1 +/- 0.05 mg Hg) but was not statistically different. We conclude that under conditions of stable membrane permeability and elevated Pmv, the plasma COP appears to be an important mechanism for protection against pulmonary edema. PMID- 2915534 TI - The influence of perfusate viscosity, RBC deformability and drag on the function of an isolated perfused rat kidney. AB - There is increasing clinical interest in improving blood rheology to optimize organ function, but studies correlating the two are scarce. To study this, rat kidneys were perfused in vitro at 37 degrees C at a constant mean renal arterial pressure of 160 mm Hg. The perfusate consisted of an oxygenated Krebs HCO3 buffer containing 1 mg/ml glucose, 0.5 mg/ml creatinine, amino acids, [3H]inulin (marker for GFR), 2.5 g/dl albumin, and 10 or 20% hematocrit. In some experiments, RBC were made nondeformable by heating at 50 degrees C for 20 min. Deformability was measured by an ektacytometer. In other experiments, 0.001% of an anionic polyacrylamide (Separan), a drag-reducing agent, was added to the perfusate. Viscosity was measured with a cone and plate viscometer, [Na+] with a flame spectrophotometer, and perfusate flow with a Brooks in-line flowmeter. Other functional parameters, GFR, urine flow, RPF, and reabsorption of sodium and water, were also measured. The results indicate that (1) making RBC nondeformable or increasing viscosity by increasing hematocrit reduces renal function, and (2) addition of a drag-reducing agent improves renal function at 20% hematocrit. We conclude that rheologic manipulation of a perfusate solution can alter flow and renal function. PMID- 2915536 TI - Brain stem topography of vagus nerve to the greater curvature of the stomach. AB - If preganglionic vagus nerve fibers enter the stomach via all of its neurovascular bundles, then proximal gastric vagotomy that divides only the bundles along the lesser curvature of the stomach neglects a potential source of innervation to the parietal cells. To determine whether or not these bundles contained preganglionic efferent vagal nerve fibers, horseradish peroxidase was applied to the central cut end of selected neurovascular bundles along the greater curvature of the stomach in rats and ferrets. Cells in the dorsal motor nucleus of the vagus (dmnX) of the rat were labeled after horseradish peroxidase applications to the right gastroepiploic, the splenic, and the short gastric bundles. The ferrets had horseradish peroxidase applied to the right gastroepiploic bundle and they also had cellular labeling of the dmnX. The labeling in cells of the dorsal motor nucleus of the vagus had a distinct topographic, rostrocaudal distribution in both species, and was maximal in the vicinity of the obex. Cells of the bilateral dmnX were labeled after horseradish peroxidase applications at all bundles. This study showed (1) that the bundles along the greater curvature of the stomach contained preganglionic efferent vagus nerve fibers, (2) that the cells of origin of these fibers were represented in the localized rostrocaudal position of the dmnX, and (3) that these fibers had their origins in the bilateral dmnX. Such nerve fibers may account for incomplete vagal denervation of the parietal cells after proximal gastric vagotomy. PMID- 2915535 TI - Traumatic shock and head injury: effects of fluid resuscitation on the brain. AB - The effects of resuscitation of traumatic-hemorrhagic shock on the brain are unknown. Traumatic shock in sheep (fracture/crush injury, 2-hr hemorrhage to 40 mm Hg) was followed by resuscitation to baseline mean arterial pressure. Two groups without brain injury were resuscitated with lactated Ringer's (LR1, n = 7) or albumin (ALB1, n = 6). Focal brain injury was added in two further groups (LR2, n = 6; ALB2, n = 6). Hemodynamics, intracranial pressure (ICP), EEG, and colloid osmotic pressure (COP) were followed. Brain water (BW) and cerebral blood volume (CBV) were compared to those of controls (C, n = 7). RESULTS: ICP rose in all groups. Animals without brain injury did not have increased brain water. Below are results for brain-injured animals after resuscitation (mean +/- SEM). (table; see text) Maintaining COP during initial resuscitation does not minimize cerebral edema: the effects of LR and ALB were similar in this setting. Focal brain injury causes edema but does not cause large increases in ICP with initial resuscitation. PMID- 2915538 TI - A skeletal muscle ventricle made from rectus abdominis muscle in the dog. AB - This study examined the ability of a skeletal muscle-powered assist ventricle to augment cardiac output in 10 dogs with experimentally induced heart failure. Heart failure was induced with the use of the beta-blocking agents atenolol and propranolol. A "skeletal muscle ventricle" was then surgically constructed by wrapping the rectus abdominis muscle, with an intact neurovascular supply, around a double open-ended compressible pouch. The skeletal muscle ventricle was then interposed in a left ventricular apicoaortic conduit. The motor nerves to the skeletal muscle ventricle were stimulated by a custom designed pulse generator and caused tetanic contraction of the ventricle during diastole of every fourth natural heart beat. Stimulation was continued for 60 min. Cardiac output, systolic and diastolic blood pressures, mean blood pressure, left ventricular end diastolic pressure, and central venous pressure were then monitored prior to, during, and several times after skeletal muscle ventricle stimulation to evaluate assist ventricle function. There was an increased cardiac output in all 10 dogs at all recording times during skeletal muscle ventricle assistance compared to the cardiac output prior to stimulation of the assist ventricle. The mean increase in cardiac output after 30 min of assist ventricle stimulation was 31.0 +/- 14% (P less than 0.01), and at 60 min was 8.0 +/- 1% (P less than 0.05). The mean diastolic blood pressure after 1 and 30 min of skeletal muscle ventricle assistance (50.0 +/- 2.9 and 48.6 +/- 2.2 mm Hg, respectively) was increased (P less than 0.05) vs the preassistance value (44.9 +/- 2.8 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2915537 TI - A statistical assessment of the dependability of transcutaneous tissue oxygen tension measurements. AB - Transcutaneous oxygen tension measurements (PtcO2) were obtained for subjects in two groups: peripheral vascular patients (N = 15) and disease-free controls (N = 9). Readings were taken in each of three locations, arm, knee and foot, in supine and erect positions, at fixed and random times, on each of 3 consecutive days. The dependability (the proportion of true variance in total variance) of PtcO2 measurements was evaluated using a generalizability model. The preliminary generalizability study analysis indicated that day-to-day variation of PtcO2 level was larger than within-day variation. Therefore, in order to decrease the measurement error variance one would preferably increase the number of days for measurements (nd) rather than increase the number of measurements within each day (nt). A decision study analysis was also performed which resulted in estimates of error variance and two interdependent dependability measures: dependability coefficients (DCs) and signal to noise ratios (S/Ns). PtcO2 dependability values were generally different for the two groups. Cases had high DCs and S/Ns (DC greater than or equal to 0.9, S/N greater than or equal to 9) in all location position combinations except for arm measurements. On the other hand, controls had low and unacceptable DCs and S/Ns (DC less than 0.8, S/N less than 4) in all location-position combinations. Cases and controls had generally lower dependability values when PtcO2 ratios were analyzed. The only two ratio-position categories for which dependability values were in the acceptable range (DC greater than or equal to 0.8, S/N greater than or equal to 4) were foot/arm erect and foot/arm supine for the cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2915539 TI - Assessment of serial carcinoembryonic antigen: determinations to monitor the therapeutic progress and prognosis of metastatic liver disease treated by regional chemotherapy. AB - It is difficult, time-consuming, and expensive to evaluate the therapeutic efficacy of regional chemotherapy of metastatic liver disease by means of imaging procedures. Therefore it was the aim of this study to find out whether serial carcinoembryonic antigen (CEA) determinations yield reliable data on the therapeutic progress and the individual prognosis of these patients. Since there exists no generally accepted modality to assess CEA curves of patients receiving chemotherapy, we developed our own criterion and tested it in a group of 35 patients. For each patient an individual reference level (CEA-means) was fixed which was obtained as the arithmetical mean of serial CEA values taken during the first three courses of chemotherapy (reference time). On the basis of CEA-means the marker curves of the 35 patients could be divided into two groups. After the reference time the CEA values of group 1 (12 patients) never decreased below CEA means. Survival of these patients was significantly (P = 0.00001) shorter than that of the 23 patients (group 2) who showed a decrease in their CEA curves below CEA-means after the reference time. Beyond this it could be observed that the improvement in survival was significantly greater in those patients who showed a CEA decrease below CEA-means for a prolonged period (3 months). This difference in prognosis is not an artefact due to different pretherapeutic conditions but is a sign of different responses to therapy. The decrease in CEA values below the individual reference level (CEA-means) is a certain sign of the efficacy of the chosen chemotherapy. A continuous rise of the CEA curve above CEA-means signifies an ineffective intrahepatic chemotherapy or extrahepatic tumor manifestation. In this case an intensive diagnostic workup of the patient and possibly a modification of the therapy are indicated. PMID- 2915540 TI - Percutaneous superfine-needle aspiration biopsy of intrathoracic lesions guided by simulator. AB - The result of percutaneous superfine-needle aspiration biopsy in 100 patients with intrathoracic lesions guided by simulator is reported. The success rate of aspiration biopsy was 94%, and no major complication was observed. The method of localization by simulator had advantages such as accuracy in localization, no limitation of mass size and site, and a high rate of puncture success. Cell smears obtained by superfine needle were similar to those obtained by fine- or large-bore needles, but fewer complications were encountered. This is a useful technique that can provide early cytological diagnosis, especially for the peripheral type of pulmonary mass. PMID- 2915541 TI - Squamous metaplasia with Hashimoto's thyroiditis presenting as a thyroid nodule. AB - A 59-year-old Japanese female presented a well-limited and movable thyroid nodule. Histologically, the nodule consisted of clusters of squamous cells surrounded by dense connective tissue in Hashimoto's thyroiditis. The squamous cells were well arranged and showed no mitotic figures. We therefore interpreted this nodule as being squamous metaplasia with Hashimoto's thyroiditis rather than squamous carcinoma of the thyroid. There are no previous reports in the literature of nodular formation of squamous metaplasia in the thyroid. PMID- 2915542 TI - Leukocyte alkaline phosphatase and carcinoembryonic antigen in breast cancer patients: clinical correlation with the markers. AB - Leukocyte alkaline phosphatase (LAP) scores in peripheral blood and plasma carcinoembryonic antigen (CEA) levels were determined in 208 breast cancer patients with nonmetastatic disease. Patients were followed until clinical manifestations of metastases appeared. Then the LAP score and CEA level were analyzed in relation to the clinical appearance of metastases. Of the 208 patients studied, 58 developed metastases during the follow-up period. The LAP scores and CEA levels of this group of patients were compared to a control group of 60 breast cancer patients who did not develop metastases. Of the two markers, LAP score seems to be considerably more useful in detecting metastatic disease. PMID- 2915543 TI - Intraoperative antegrade irrigation in complicated left-sided colonic cancer. AB - Emergency one-stage surgery for acute, complicated, left-sided colonic cancer can be performed because of intraoperative antegrade irrigation of the large intestine. This procedure was performed in 17 patients: 15 patients with an obstructive, left-sided cancer and two patients with a perforated carcinoma. The age distribution ranged between 57 and 92 years. There were two postoperative septic complications: a small wound abscess and a partial abdominal wall dehiscence. One patient died because of massive upper gastrointestinal bleeding. This method permits the creation of a primary anastomosis in the left colon, obviating the necessity of a coeco- or colostomy, preternatural anus, or an extensive right-sided hemicolectomy. Several surgical interventions are avoided, resulting in a decrease of mortality, morbidity, duration of hospital stay, and costs. Moreover, intraoperative irrigation could be an attractive alternative for the usual preoperative mechanical bowel preparation, which is especially burdensome in elderly patients. PMID- 2915544 TI - Vaccinia virus-infected C-C36 colon tumor cell lysates stimulate cellular responses in vitro and protect syngeneic Balb/c mice from tumor cell challenge. AB - Vaccinia virus (VV) was used to infect and lyse the Balb/c colon tumor line C-C36 to prepare oncolysate (VCO) with augmented immunogenicity. Mice treated with VCO and challenged with C-C36 were significantly protected against tumor growth as compared to untreated controls (P less than 0.001) and mice treated with CO (P less than 0.01). Moreover, protection induced by VCO was specific when growth inhibition of C-C36 was compared to that of meth-A (P = 0.027). Splenocytes from mice stimulated with VCO in vitro showed greater proliferation than splenocytes stimulated with CO alone or VV alone, suggesting induction of a unique VCO component. Additional evidence for a specific response was suggested by the observation that splenocytes stimulated with VCO in vitro demonstrated augmented cytolysis of C-C36 but did not show cytolytic activity against unrelated target cells. However, augmented cytolysis of the natural killer (NK)-sensitive YAC-1 by VCO-stimulated splenocytes was also observed. These results suggest that in vivo resistance to tumor challenge induced by VCO treatment may result from stimulation of both specific and nonspecific effector cells. PMID- 2915545 TI - 18th annual UCLA symposium. Abstracts: Frontiers of NMR in molecular biology. PMID- 2915547 TI - 18th annual UCLA symposium. Abstracts: New directions in biological control. PMID- 2915546 TI - 18th annual UCLA symposium. Abstracts: Glycobiology. PMID- 2915548 TI - 18th annual UCLA symposium. Abstracts: Immunogenicity. PMID- 2915549 TI - 18th annual UCLA symposium. Abstracts: Protein and pharmaceutical engineering. PMID- 2915550 TI - 18th annual UCLA symposium. Abstracts: Genetic mechanisms in carcinogenesis and tumor progression. PMID- 2915551 TI - 18th annual UCLA symposium. Abstracts: Transgenic models in medicine and agriculture. PMID- 2915552 TI - 18th annual UCLA symposium. Abstracts: Early embryo development and paracrine relationships. PMID- 2915554 TI - 18th annual UCLA symposium. Abstracts: Growth regulation of cancer-II. PMID- 2915553 TI - 18th annual UCLA symposium. Abstracts: Cellular and molecular biology of normal and abnormal erythroid membranes. PMID- 2915555 TI - A clinical study of cerebral circulation during extracorporeal circulation. AB - The objective of this study is to clarify the relationship of cerebral blood flow to extracorporeal circulation flow and mean arterial pressure during nonpulsatile extracorporeal circulation under moderate hypothermia. Cerebral blood flow was determined by an argon saturation and desaturation method after that of Pevsner and colleagues with a mass spectrometer in 21 adult patients undergoing cardiac operations. Cerebral blood flow was 25, 33, 35, and 42 ml/100 gm/min, ranging from 19 to 50 ml/100 gm/min, at extracorporeal circulation flow rates of 40, 50, 60, and 70 ml/kg/min, respectively. Cerebral blood flow increased proportionally to extracorporeal circulation flow. Cerebral blood flow scattered almost transversely to mean arterial pressure and was 31 ml/100 gm/min in a hypotensive group (mean arterial pressure 34 to 50 mm Hg) and 34 ml/100 gm/min in another group (mean arterial pressure 51 to 94 mm Hg). Mean arterial pressure did not significantly influence cerebral blood flow. Cerebral oxygen consumption did not remarkably decrease and remained in the reasonable range when cerebral blood flow was 23 to 40 ml/100 gm/min. Subsequently, we assumed that the average cerebral blood flow value of 25 ml/100 gm/min at an extracorporeal circulation flow rate of 40 ml/kg/min also would be in the safe range. All of the patients are living without cerebral complications. We conclude that (1) cerebral blood flow was extracorporeal circulation flow dependent and (2) cerebral blood flow in the safe range was maintained even in the hypotensive range, provided the extracorporeal circulation flow rate was 40 ml/kg/min or higher. PMID- 2915556 TI - The effect of transfusion of fresh whole blood versus platelet concentrates after cardiac operations. A scanning electron microscope study of platelet aggregation on extracellular matrix. AB - To evaluate the effect of fresh whole blood transfusion versus platelet concentrates transfusion on platelet aggregation after cardiac operations, 24 patients were randomized to receive either one unit of fresh whole blood (12 patients) or 10 platelet units (12 patients) after cardiopulmonary bypass. Platelet aggregation on extracellular matrix, platelet count, and mean platelet volume were studied preoperatively, at termination of cardiopulmonary bypass, after protamine administration, and after the transfusion of fresh whole blood or after transfusion of each two platelet units. Extracellular matrix produced by cultured bovine corneal cells closely resembles the vascular subendothelial basal lamina, and is an ideal in vitro model in the study of platelet interaction with the subendothelium. Platelet aggregation on extracellular matrix, studied by a scanning electron microscope, was graded from 1 to 4, wherein grade 1 represents nonactivated platelets and grade 4 a mature platelet aggregate. With this grading system, the two groups were similar in preoperative values (3.3 +/- 0.9 versus 3.7 +/- 0.4) and values after cardiopulmonary bypass (1.5 +/- 1.0 in both groups). One unit of fresh whole blood restored platelet aggregation on extracellular matrix to preoperative status (3.0 +/- 1.0), whereas eight platelet units were needed for the same result (3.2 +/- 0.8). One unit of fresh whole blood increased platelet count in a manner similar to that achieved by six platelet units and increased mean platelet volume to a level higher than that achieved by 10 platelet units. These results suggest that the effect of one unit of fresh whole blood on platelet aggregation after cardiopulmonary bypass is at least equal, if not superior, to the effect of 8 to 10 platelet units. PMID- 2915557 TI - Protection of the myocardium during global ischemia. Is crystalloid cardioplegia effective in the immature myocardium? AB - In pediatric cardiac operations, a high proportion of hospital deaths are believed to result from inadequate myocardial protection during the period of global ischemia. To investigate whether this may be due to an inherently lower resistance to myocardial ischemia or to the failure of conventional cardioplegia to afford adequate protection in the immature heart, we have conducted a series of studies with isolated hearts from neonatal (3 to 5 days old, body weight 6.3 to 13.4 gm) and adult (84 to 112 days old, 260 to 340 gm) rats. The efficacy of cardioplegia was assessed in neonatal hearts (n = 6 per group) subjected to various durations of normothermic ischemia, with and without a 2-minute preischemic infusion of the St. Thomas' Hospital cardioplegic solution. At all times studied, the use of cardioplegia resulted in a greater postischemic recovery of left ventricular developed pressure and first derivative of left ventricular pressure. After periods of ischemia lasting 30, 60, 90, 120, and 150 minutes in the absence of cardioplegia, left ventricular developed pressure recovered to 80% +/- 10%, 66% +/- 11%, 53% +/- 7%, 33% +/- 6%, and 21% +/- 4% of preischemic values, respectively; in the presence of cardioplegia, the values were 89% +/- 6%, 83% +/- 8%, 74% +/- 6% (p less than 0.05), 58% +/- 5% (p less than 0.05), and 41% +/- 7% (p less than 0.05), respectively. The corresponding values for first derivative of left ventricular pressure were 78% +/- 9%, 67% +/- 12%, 54% +/- 7%, 30% +/- 5%, and 19% +/- 3% in the absence of cardioplegia and 92% +/- 7%, 88% +/- 8%, 75% +/- 8%, 56% +/- 5% (p less than 0.05) and 39% +/- 6% (p less than 0.05) in the presence of cardioplegia. In the noncardioplegia groups, 90% of hearts exhibited ischemic contracture (mean time to onset = 24.7 +/- 1.1 minutes), whereas in the cardioplegia groups, only 63% exhibited contracture, and of a significantly delayed onset (37.0 +/- 1.5 min, p less than 0.05). Adult hearts (n = 5) subjected to 30 minutes of normothermic ischemic arrest, in the absence of cardioplegia, recovered 36% +/- 7% of the preischemic left ventricular developed pressure and 37% +/- 9% of the preischemic first derivative of left ventricular pressure on reperfusion; 100% of these hearts exhibited some degree of contracture (mean time to onset = 15.4 +/- 1.1 minutes) by the end of the ischemic period.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2915558 TI - Comparison of single dose versus multiple dose crystalloid cardioplegia in neonate. Experimental study with neonatal rabbits from birth to 2 days of age. AB - Thirty-five isolated hearts from newborn rabbits (aged birth to 2 days) were subjected to 120 minutes of ischemia at 15 degrees C with high potassium crystalloid cardioplegia. They were divided into four groups according to the method of cardioplegic administration: group C (preischemic control, n = 9), group S (single dose, n = 10), group M-1 (multiple dose, infused every 40 minutes, n = 7), and group M-2 (multiple dose, infused every 20 minutes, n = 9). After 30 minutes of reperfusion, the heart rate, coronary flow, creatine kinase release, percent water content, and myocardial ultrastructural scores for mitochondrial damage and intracellular edema were compared among the four groups. All of these parameters except coronary flow were significantly poorer in group M 2 than in groups C and S (p less than 0.05). The mitochondrial damage and intracellular edema scores were significantly poorer in group M-1 than in group C (p less than 0.05). No significant differences in these two scores were seen between group S and group C and between group S and group M-1. These results indicate that the single dose method of administering crystalloid cardioplegia may provide better myocardial protection than the multiple dose method in the neonate. PMID- 2915560 TI - The value of mediastinoscopy in preoperative staging of bronchogenic carcinoma. AB - To determine more precisely the role of mediastinoscopy in the preoperative staging of bronchogenic carcinoma, we studied 85 patients in the period 1983 to 1985 and compared the results of mediastinoscopy and computed tomographic scanning with the findings at thoracotomy. Mediastinoscopy was performed in 48 patients when mediastinal nodes larger than 1 cm were found at computed tomographic scanning. Only 21 of them (44%) were found to have metastatic nodes. Of the remaining patients, 22 were operated on and two showed false negative results (9%). Mediastinoscopy had a sensitivity of 91% and a specificity of 100%. The positive predictive value of computed tomographic scanning was only 54%. Thirty-seven patients underwent thoracotomy after having negative computed tomographic scan results. Eleven of them (30%) were found to have metastatic mediastinal lymph nodes. The negative predictive value of computed tomographic scanning was 70%. When results from both series of patients were compared, the sensitivity and specificity of computed tomographic scanning proved to be 68% and 57%, respectively, with an accuracy of 61%. Because of the low accuracy rate of computed tomographic scanning, a more routine use of mediastinoscopy seems to be justified. PMID- 2915559 TI - Loss of platelet fibrinogen receptors during clinical cardiopulmonary bypass. AB - In 10 patients, cardiopulmonary bypass decreased the number of fibrinogen binding sites from 31,730 +/- 12,802 per platelet to 18,590 +/- 9,644 per platelet. Bypass also decreased the amount of the platelet membrane glycoprotein IIIa, which is part of the fibrinogen receptor complex, from 17.1 +/- 3.6 ng/10(9) platelets to 12.9 +/- 4.7. The fibrinogen binding constant did not change. Platelet sensitivity to adenosine diphosphate did not change; however, template bleeding times increased from 5.2 +/- 1.5 minutes before bypass to 8.5 +/- 2.3 minutes after bypass. Analysis of detergent washings from the perfusion circuit after bypass in five patients indicated that platelet material remains attached to the surface as membrane fragments and degranulated platelets. These data further elucidate the mechanism of platelet loss and dysfunction during cardiopulmonary bypass and highlight the importance of platelet membrane fibrinogen receptors and surface adsorbed fibrinogen in this process. PMID- 2915561 TI - Prognostic implications of histopathologic subtyping in patients with surgically treated stage I or II adenocarcinoma of the lung. AB - The prognostic impact of histopathologic subtyping of pulmonary adenocarcinoma according to the World Health Organization classification was evaluated among 137 consecutive patients with radically resected stage I or II tumors. Median observation time in the 55 patients who are alive is 47 months (range 25 to 80). All tumors were subtyped, the most frequent being acinar adenocarcinoma (57% of patients), followed by bronchioloalveolar carcinoma (18%), solid carcinoma with mucus formation (14%), and papillary adenocarcinoma (12%). Patients having bronchioloalveolar carcinoma had the longest median survival (44 months), while survival was shortest for patients having solid carcinoma with mucus formation (median 10 months); in this latter group there were significantly fewer 1-year survivors compared with all other subtypes. Survival time was intermediate for patients having acinar and papillary adenocarcinoma (medians 31 and 32 months). Patients with solid carcinoma with mucus formation have an unfavorable prognosis and may be considered potential candidates for studies on adjuvant therapy, although the relative influence of other prognostic factors may be considered as well. PMID- 2915562 TI - Improvement of myocardial function by trifluoperazine, a calmodulin antagonist, after acute coronary artery occlusion and coronary revascularization. AB - Activation of an intracellular calcium-calmodulin complex may play an important role in myocardial injury induced by ischemia and reperfusion. Trifluoperazine, a calmodulin antagonist, was used before ischemia to enhance myocardial preservation by preventing intracellular calcium accumulation. The experimental model used an isolated in situ pig heart (19 control animals and 15 trifluoperazine-treated animals) subjected to occlusion of the left anterior descending coronary artery for 60 minutes followed by 60 minutes of hypothermic potassium crystalloid cardioplegic arrest and 60 minutes of reperfusion. Myocardial segmental function measured by ultrasonic crystals showed that active systolic segment shortening was abolished in the distribution of the left anterior descending artery after 60 minutes of occlusion irrespective of the treatment, whereas that not in the distribution of the left anterior descending artery increased by about 15% in both groups of animals. Restoration of systolic segment shortening in the distribution of the left anterior descending artery 60 minutes after reperfusion was 12% and 42% of baseline levels in untreated and trifluoperazine-treated animals, respectively (p less than 0.01). This improvement in segmental function by trifluoperazine was reflected in significantly (p less than 0.05) better global myocardial contractility and compliance and in significantly (p less than 0.01) greater total coronary blood flow and myocardial oxygen consumption. Trifluoperazine also increased myocardial creatine phosphate content in the distribution of the left anterior descending artery (p less than 0.01) during reperfusion, and creatine kinase release was reduced (p less than 0.05). Our results suggest that trifluoperazine improved regional myocardial function after acute occlusion of the left anterior descending artery and reperfusion and that global cardiac performance was thereby improved. The beneficial effects of trifluoperazine may be exerted by prevention of myocardial injury associated with the calcium-calmodulin complex in ischemic and reperfused myocardium. PMID- 2915563 TI - Mediastinal infection after cardiac operation. A simple closed technique. AB - From March 1984 to March 1987, a simple closed method, previously described for the treatment of osteomyelitis after orthopedic operations, was used to treat deep sternal infection in 11 patients. The basis of this technique is, after meticulous debridement of the wound, to drain all the infected areas with small catheters connected to a bottle inside of which a strong (700 mm Hg) negative pressure is created (Redon drainage device). The method does not require irrigation. The maximum duration of the drainage was 24 days and complete recovery was obtained in all patients without further surgical treatments. The comfort of the patients was optimal. PMID- 2915564 TI - Chronotropic and inotropic supports are both required to increase cardiac output early after corrective operations for tetralogy of Fallot. AB - To assess the respective roles of chonotropism, inotropism, and afterload reduction in increasing cardiac index early after corrective operations for tetralogy of Fallot, we measured vascular pressures and cardiac output and evaluated left ventricular dimension changes before and after a 35% rise in heart rate over baseline. This rise was induced by atrial pacing with intact atrioventricular conduction, isoproterenol, or atrial pacing together with dobutamine. With atrial pacing, left ventricular end-diastolic diameter decreased (38.7 +/- 4.3 to 34.2 +/- 5.6 mm, p less than 0.05), the shortening fraction (ratio of the difference between left ventricular end-diastolic and end-systolic diameters to left ventricular end-diastolic diameter) remained constant, and stroke volume index was reduced (28.8 +/- 4.5 to 19.7 +/- 4.6 ml/m2, p less than 0.05). As a result, cardiac index was left unchanged. When dobutamine was added as supplemental inotropic support, left ventricular end-diastolic diameter remained constant, shortening fraction increased (30% +/- 5.4% to 36% +/- 3.3%, p less than 0.05), and cardiac index rose significantly (3.04 +/- 0.61 to 4.18 +/- 0.85 L/min/m2, p less than 0.05). Heart rate acceleration with isoproterenol, combining chronotropism, positive inotropic support, and afterload reduction, slightly increased left ventricular end-diastolic diameter, significantly raised shortening fraction, and markedly enhanced cardiac index (3.03 +/- 0.55 to 4.9 +/ 1.09 L/min/m2). Atrial pacing with intact atrioventricular conduction, as an isolated chronotropic stimulus, is not suited to increase cardiac index early after operations for tetralogy of Fallot unless additional inotropic support is simultaneously provided. PMID- 2915565 TI - Pulmonary dirofilariasis. The largest single-institution experience. AB - Pulmonary dirofilariasis caused by Dirofilaria immitis, the dog heartworm, is a rarely reported pulmonary lesion. It appears as a solitary pulmonary nodule, and the diagnosis is not established until thoracotomy and subsequent histologic examination of the specimen are performed. Sporadic reports of pulmonary dirofilariasis in the United States total only 70 cases. The six resections of pulmonary dirofilariasis at the Ochsner Clinic represent the largest reported series of cases originating at a single institution. We present an overview of the pathogenesis of this disease, its clinical manifestations, pathologic and epidemiologic features, and geographic distribution. The prevalence of pulmonary dirofilariasis appears to be increasing; hence, thoracic surgeons and pathologists need to be alert to this cause of granulomatous pulmonary lesions. PMID- 2915566 TI - Traumatic pulmonary pseudocyst. Report of twelve cases. AB - Twelve cases of traumatic pulmonary pseudocyst were seen between January 1966 and July 1987 at Saiseikai Kanagawaken Hospital. The cause of the traumatic pulmonary pseudocyst was closed blunt chest trauma in all patients. For the first few days after the injury, computed tomographic scan was more useful in diagnosis than chest roentogenogram. Tube drainage of the pleural cavity was performed in 10 patients who had hemothorax or hemopneumothorax, and antibiotics were administered to all patients. No patient underwent a surgical procedure, and all traumatic pulmonary pseudocysts eventually resolved, without any specific treatment, within 1 to 4 months (average 1.8 month) after the trauma. We conclude that pulmonary resection is not indicated except in the rare instance in which the traumatic pulmonary pseudocyst becomes infected. PMID- 2915567 TI - Comparison of early and late dimensions and arrhythmogenicity of cryolesions in the normothermic canine heart. AB - Little is known about myocardial cryoablation at normothermia and the effect of cryoprobe head size and duration of freeze on final lesion volume. In the present study, cryolesions were created with a carbon dioxide cryoprobe with two head sizes (cylindrical head 6 mm diameter and large circular head 18 mm diameter) in the normothermic canine heart during cardiopulmonary bypass. The duration of freeze (exposure time) varied from 2 to 3 or 4 minutes and the effects on immediate and chronic lesion size were evaluated. Lesions produced by epicardial exposures were compared with intramyocardial lesions created by placing the cylindrical head in a 6 mm stab incision. A minimum of four lesions were created in each dog. Lesion size was evaluated at 0 minutes (iceball) and 24 hours (two dogs), 7 days (one dog), or 4 weeks (five dogs). Iceball diameter was approximately 5 mm larger than chronic lesion diameter regardless of head size or exposure time. Prolongation of exposure time from 2 to 3 minutes resulted in significant increases in the volume of epicardial lesions (cylindrical head: 280 +/- 100 mm3 versus 740 +/- 200 mm3, p = 0.001; circular head: 1200 +/- 100 mm3 versus 2300 +/- 500 mm3, p = 0.007) because of increases in diameter and depth. No further increase in lesion size was observed when exposure time was prolonged from 3 to 4 minutes. A 3-minute intramyocardial exposure with the cylindrical head placed in a stab incision enabled production of transmural lesions (16 +/- 2 mm deep). Two and 4 weeks postoperatively, dogs underwent electrophysiologic study from the right and left ventricular apices. No animals had inducible ventricular tachycardia despite the heterogeneous configuration of the multiple cryolesions. In conclusion, it is possible to produce rapid and predictable ablation of clinically useful volumes of myocardium during normothermic bypass with the use of currently available equipment. Under these conditions, an exposure time of 3 minutes is optimal for a liquid carbon dioxide cryoprobe. Cryolesions should be overlapped by at least 2.5 mm to produce continuous areas of ablation. Multiple cryolesions do not form a chronic substrate for ventricular tachycardia. PMID- 2915568 TI - Aneurysm of aberrant right subclavian artery and Ondine's curse. PMID- 2915569 TI - Pressure monitoring after cardiopulmonary bypass. PMID- 2915570 TI - Acquired benign bronchoesophageal fistula in an adult. PMID- 2915571 TI - The use of a temporary vein graft to assure adequate myocardial protection before the definitive internal mammary-coronary artery anastomosis in coronary artery reoperations. PMID- 2915572 TI - Effects of simultaneous and sequential exposure to granulocytic and monocytic inducers on the choice of differentiation pathway in HL-60 promyelocytic leukemia cells. AB - HL-60 promyelocytic leukemic cells were induced to differentiate by the combination of two alternative inducers: phorbol-12-myristate 13-acetate (PMA) and either dimethyl sulfoxide (DMSO) or retinoic acid (RA). Simultaneous exposure to optimal concentrations of PMA and either DMSO or RA potentiated PMA-induced differentiation into monocyte-macrophages. Granulocytic inducers combined with lower concentration of PMA competed with the latter for the differentiation pathway, producing monocyte-macrophages, granulocytes, paramyeloid and giant multinucleated cells. Lineage specificity of cells treated sequentially with two discrete exposures to alternative inducers depended on the order of exposure. The first exposure initiated differentiation into the pathway specific for the inducer used. The second exposure determined lineage specificity and stimulated terminal differentiation. Thus, treatment with RA for 24-72 h followed by PMA resulted in monocyte-macrophage differentiation; reversed order of exposure resulted in granulocytic differentiation. The switch in the differentiation pathway occurred at the relatively advanced stages of differentiation. PMID- 2915573 TI - A case-control study of aplastic anemia. AB - A case-control interview study of aplastic anemia was conducted to evaluate suspected risk factors. Cases (N = 59) newly diagnosed during 1975-82 at 25 Baltimore area hospitals were compared with 59 individually matched (on age, sex and race) controls selected by random digit dialing. The average educational level was less for cases than controls. The major job-related findings were a significant excess for occupational exposure to paint (OR = 6.1; 95% C.I. = 1.2 29.7), further substantiated by a positive dose-response relationship, although painters were not at excess risk. An increased risk of occupational exposure to viruses (OR = 9.0; 95% C.I. = 0.8-105.6) was noted. Additional evidence implicating viral factors included a significant association with prior history of hepatitis (OR = 9.0; 95% C.I. = 1.0, 84.2) and an elevated risk for pre diagnostic receipt of blood transfusions (OR = 7.1; 95% C.I. = 0.7-68.4). Risks were not increased for other occupational, residential, personal, or medical treatment exposures or for other viral infections, medical conditions, smoking or alcohol consumption prior to diagnosis. Because of the small number of subjects studied and the multiple comparisons examined, these findings should be interpreted cautiously and confirmation should be undertaken in larger, population-based studies. PMID- 2915574 TI - Increased sensitivity to 1-beta-D-arabinofuranosylcytosine in P388 murine leukemic cells resistant to etoposide. AB - A variant P388 murine leukemic cell resistant to 4'-demethylepipodophyllotoxin-9 (4,6-O-ethylidine)-beta-D-gl ucopyranoside (etoposide) (VP-16-213) was cloned. The variant P388/VP-16 cell line was 159-fold resistant to VP-16. We found that this variant P388/VP-16 cell line showed collateral drug sensitivity to 1-beta-D arabinofuranosylcytosine(Ara-C), determined by comparing the 50% inhibitory concentrations in 48-h growth inhibition assay. To clarify the mechanism of this increased sensitivity to Ara-C, we quantified the deoxyribonucleoside triphosphate pools and 1-beta-D-arabinofuranosylcytosine triphosphate(Ara-CTP) using high-performance liquid chromatography in the parent and drug-resistant sublines of P388 cells. The analysis of deoxyribonucleoside triphosphate pools revealed that the pyrimidine triphosphate pools were significantly decreased in the P388/VP-16 cell line and the Ara-CTP concentration of two variant cell lines were not significantly different. The Ara-CTP/dCTP ratio was significantly increased in P388/VP-16 cells. These data suggest that the inhibition of the dCTP de-novo pathway and the preservation of the dCTP salvage pathway in P388/VP-16 cells might correlate with the increased sensitivity to Ara-C. PMID- 2915575 TI - Oncogene expression in Rauscher murine leukemia virus induced erythroid, myeloid and lymphoid cell lines. AB - A comparative study on the expression of nuclear and cytoplasmic oncogenes was carried out using the Northern blotting technique, in Rauscher virus induced primary leukemias and the more malignant transformed cell lines derived from them. The latter grow permanently in vitro. Hyperplastic spleens obtained from mice recovering from anemia were analysed as controls. In addition to the detection of mRNAs, Southern blotting was carried out to observe whether rearrangement or amplification of oncogenes had occurred. The results show that the nuclear oncogenes c-myc, c-myb and p53 are strongly expressed in leukemic tissue, whereas c-fos transcripts show a much weaker hybridization. The expression of two of these oncogenes, c-myc and c-myb was followed during differentiation in myeloid leukemic cells and showed a gradual decrease when compared with the actin gene, which is constitutively transcribed. A large number of cytoplasmic oncogenes is expressed in the leukemic cells lines, i.e. c-abl, c fms, c-fes, c-src, c-ros, c-H-ras, c-K-ras and N-ras. Of these, transcripts coding for c-abl and c-src were absent in blast cells of acute erythroid leukemias. Transcripts coding for c-erb, c-mos and c-sis could also not be detected. A number of putative oncogenes which are reported to play a role in Moloney and Friend virus induced leukemias for instance pim-1, fis-1, fim-1 and fim-2 were also used for screening. Only expression of pim-1 in Rauscher virus induced myeloid leukemic cells and in primary acute erythroid leukemias could be observed. At the DNA level no rearrangement or amplification of any of the oncogenes investigated could be detected. The results show that a number of oncogenes are expressed simultaneously in the same leukemic tissue or cell lines. It therefore seems likely that the presence of transcripts of different oncogenes is associated with the progression of leukemia, but is not the primary cause of leukemogenesis or of the transformation of these cells into established cell lines. PMID- 2915576 TI - Cytotoxic effects on viable human leukemic cells by combinations of lymphokine activated killer cells and monoclonal antibodies. AB - Earlier studies with individually phenotyped monoclonal antibody combinations and complement or lymphokine activated killer (LAK) cells showed that many acute myeloid leukemic cells were resistant to these cytotoxic agents when used singly. Therefore, a combination of both agents was studied. When the leukemic target cells were submitted to killer cells activated with 100 or 800 IU of recombinant interleukin-2 (rIL-2), only averages of 6.0 and 16.7% of the targets were killed respectively. When the remaining, refractory cells were confronted with a cocktail of individually phenotyped monoclonal antibodies and complement, an additional significant cell kill was obtained, but it amounted to only between 7.4 and 5.5% (for LAK-100 and LAK-800, respectively). In contrast, of the target cells initially refractory to the same cocktail of monoclonal antibodies, all were cross-resistant both to LAK-cells activated with 100 and to those activated with 800 IU of rIL-2. This cross-resistance was caused neither by sub-optimal LAK cell activation, nor by antibody blocking of hypothetical LAK-cell receptors, since pre-incubation with monoclonal antibodies without complement did not inhibit LAK-cell cytotoxicity. Although only partial cross-resistance was found in the present study, it still remains that only a minority of the tumor cells could be killed. A higher in-vitro cell kill should be attempted prior to clinical trials in order to avoid clinical effects resembling those of a partial surgical tumor resection. PMID- 2915578 TI - [Quality circles in health care. To scrutinize your own organization]. PMID- 2915577 TI - [Forensic psychiatry and emergency health services are in the same situation]. PMID- 2915579 TI - [Vaccination trends]. PMID- 2915580 TI - [A sound knowledge of psychotherapy doesn't make up for deficient knowledge of psychopharmacology]. PMID- 2915581 TI - [Management of hyperlipidemia: diet and drugs are complementary to each other]. PMID- 2915582 TI - [Diagnostic registries of tobacco use--the use of diagnosis 305 B!]. PMID- 2915583 TI - [Alcohol. The genetic background of alcohol dependence and alcoholism]. PMID- 2915584 TI - [Drainage in pneumothorax]. PMID- 2915585 TI - [The Orebro pleural drainage constructed at the clinic]. PMID- 2915586 TI - [Vaccines--today and tomorrow]. PMID- 2915587 TI - [Medical ethics. Medical priority ethics in the face of diminishing resources. The allocation of medical care is unfair towards the elderly. 144 minutes of unpaid sick-leave due to the common cold could cover dialysis costs]. PMID- 2915588 TI - [Surgical therapy of blepharospasmus gravis]. AB - Blepharospasm is a rather rare disease characterised by cramps of the orbicularis oculi muscle. The quality of life of patients suffering from this illness is often severely reduced. The therapeutic approaches reported in the literature have so far not been satisfactory in most cases. In the mid'-seventies a new operative technique has been introduced by Walser and modified by Behbehani. This procedure consists of the dissection of the zygomatico-temporal branch of the facial nerve. In the present paper the author reports on his own experience with this special method as well as the long-term results in 19 patients that have been followed up over a period of 3 months up to 14 years after operation. Surgery was carried out bilaterally in 19 cases, while 5 patients were operated on one side only. After resection of the nerve, blepharoplasty of the upper lid was performed. The therapeutic value of the technique is discussed and compared with the appropriate literature. PMID- 2915589 TI - [Laser light-induced cytotoxicity of cultivated squamous cell cancer cells of the head and neck following photosensitization]. AB - Photodynamic therapy, which involves the action of light-activated dyes on biological tissues, has been attempted to treat tumors. In order to achieve effective tumor cell destruction in head and neck cancer, the direct photodynamic effects on in vitro cultured squamous carcinoma cell lines were analyzed. Without light no tumor cell killing was observed after photosensitization up to 6 hrs with dihematoporphyrinester/-ether (DHE) concentrations of 5 micrograms/ml. With longer incubation times and higher light irradiation dosages, however, an increasing cytotoxicity could be observed. Optimal intervals for photosensitization were 48 hours. Squamous cell carcinoma lines of the head and neck from different locations did not differ in their photodynamic behaviour with respect to photodynamic treatment. With the results presented, it will be appropriate to complete in vivo studies to inspire photodynamic tumor cell destruction in the treatment of head and neck cancer as a new approach besides the classical therapeutic modalities. PMID- 2915590 TI - [Animal experiment studies of collateral reinnervation of denervated laryngeal musculature]. AB - The course of atrophy of type I and type II muscle fibers of the posterior cricoarytenoid muscle, the lateral cricoarytenoid muscle and the medial thyroarytenoid muscle of 9 dogs have been investigated after resection of the ipsilateral recurrent laryngeal nerve after 2, 4 and 10 months. Using ATP-ase staining the histochemical results revealed a predominant atrophy of type II fibers, a reactive hypertrophy of type I fibers after a period of 4 months and a pattern of type-grouping with signs of a complete reinnervation in all laryngeal muscles within 10 months. The existence of a supplementary innervation of the intrinsic laryngeal muscles in dogs and its implication on experiments in laryngeal reinnervation are discussed. PMID- 2915591 TI - [The voice of the singer in the phonetogram]. AB - Phonetograms were subdivided into areas approximating voice registers. By means of an analytical description of the areas, parameters could be established for a differentiation of voice categories and efficiency. The evaluation of 21 untrained and 34 trained voices showed a significant difference between the two groups. Male singers demonstrated more efficiency in the head and chest registers than male non-singers; female singers showed a stronger efficiency only in the head voice in comparison with their non-singer counterparts. Proceeding from voice sound alone, voices are often misclassified regarding the voice categories, and voice problems arise. Moreover, enhanced training of only chest or head voice function results in functional disorders in the singing voice. Such cases can be demonstrated by means of phonetograms. PMID- 2915592 TI - [Implementing ENT medical expert testimony in hit-and-run offenses]. AB - The precondition to enforce a correct ENT hit-and-run expertise is knowledge of loudness and frequency of the noise of the bump. The exact anamnesis about type of car and noise production in the car such as air condition or radio helps the expert to calculate the background noise and the noise of the bump close by the ears of the driver. Measurements of the pure tone audiogram with additional wideband background noise simulating the calculated background noise in the car should be carried out in the defendant. Important is also the performance in frequency selectivity of the person indicted for hit-and-run offence. A reduction in frequency resolution proficiency reduces the loudness of the noise of bump. PMID- 2915593 TI - [Otogenic complications with a normal, intact tympanic membrane]. AB - Complications originating from the petrous bone may occur in the absence of any tympanic membrane pathology. This is known from a couple of cases in the literature and is underlined by two own case reports. Today, computed tomography and/or magnetic resonance imaging play a major role in the diagnosis of such rare but dangerous diseases. PMID- 2915594 TI - A seasonal pineal peptide rhythm persists in superior cervical ganglionectomized rats. AB - Neurohypophyseal peptide hormone activity is present in the pineal gland of mammals, and varies over a seasonal cycle. Pineal peptide levels, measured by arginine vasotocin (AVT) radioimmunoassay, increase dramatically for a brief time during August each year. The manner in which this cycle is regulated is as yet unknown. Input to the pineal from sympathetic axons arising in the superior cervical ganglia (SCG) is essential for the generation and regulation of the circadian rhythm in melatonin synthesis, and is the only pathway known to regulate pineal biochemical processes. It was of interest then to determine the impact of the SCG on the seasonal peptide cycle. Levels of pineal arginine vasotocin immunoactivity (iAVT) were monitored during August, 1984, in rats which had been superior cervical ganglionectomized (SCGX), in sham-operated and intact controls (L:D 12:12), and in rats subjected to L:D 22:2. The results indicate that SCGX does not abolish the seasonal cycle, but may influence the timing of the iAVT peak. Inhibition of pineal melatonin synthesis by exposure of rats to L:D 22:2 did not mimic the phase delay seen with SCGX, but did cause a significant increase in the amplitude of the August iAVT activity peak. PMID- 2915595 TI - Brain cholecystokinin depletion in rats with acute liver failure. AB - A decrease of both hypothalamic and cortical CCK occurred in the brain of rats killed 8 hours after hepatic artery ligation following portocaval anastomosis. Brain CCK depletion was not reproduced by exogenously provoked hyperammonemia nor by insulin-induced hypoglycemia, thus suggesting a central mechanism for the derangement of the CCKergic system in the course of acute liver failure. PMID- 2915596 TI - The effect of etorphine on the secretion of endogenous catecholamines and total tritium evoked by nerve- and acetylcholine-stimulation in perfused rat adrenal glands. AB - Isolated perfused rat adrenal glands were prelabeled with 3H-norepinephrine and catecholamine secretion was evoked by nerve stimulation (10 Hz, supramaximal voltage for 30 seconds) or acetylcholine (ACh)(5.4 micrograms) injection. Nerve stimulation evoked significant increases in tritium (16371 +/- 2109 cpm) and catecholamine (11.5 +/- 1.0 ng norepinephrine [NE], 123.1 +/- 13.0 ng epinephrine [EP]) release from the adrenal medulla. ACh injection evoked catecholamine release, but failed to increase tritium release. In the presence of etorphine, the nerve stimulation-mediated release of tritium, NE and EP was inhibited. In contrast, the ACh-mediated release of NE but not EP was inhibited by etorphine. In a previous publication (1), we have shown that 3H-NE is taken up by sympathetic nerve endings contained in extra adrenal tissue removed along with the adrenal gland during the surgery, but not by chromaffin cells. Therefore, the inhibitory effect of etorphine on NE, EP and tritium release evoked by nerve stimulation suggests a functional role for opiate receptors on transmitter release from sympathetic and splanchnic nerve endings. However, the differential effect of etorphine on NE and EP release evoked by ACh injection indicates that opiate receptors on chromaffin cells modulates NE but not EP release. PMID- 2915597 TI - Changes in body weight and body surface area in strain 13 guinea pigs infected with Pichinde virus. AB - In studying pathogenetic mechanisms of Pichinde virus-induced disease in strain 13 guinea pigs, a large decrease of body weight (approximately 28%) observed within 14 days postinoculation raises a question concerning the validity of standardizing body or organ functions in terms of body weight. This study was to examine changes in body weight and body surface area of Pichinde virus-infected strain 13 guinea pigs after various days postinoculation. Control guinea pigs were also subjected to the same experimental procedures and experimental days. While body weights and body surface areas increased progressively in controls, I observed only slight decreases in body surface areas (4-6%) in the infected guinea pigs, despite large decreases of body weights throughout the 14-day experimental period. In conclusion, Pichinde virus-infected strain 13 guinea pigs demonstrated a small reduction of body surface area within 14 days postinoculation, suggesting that body surface area, rather than body weight, should be used for standardizing body or organ functions for comparison with their own baseline values. PMID- 2915598 TI - A radiolabel and electron microscopy study of the interaction of liposomes with synaptosomal membranes. AB - The quantitative and qualitative interaction of liposomes with synaptosomes isolated from rat brain was examined using radiolabeled phospholipids and electron microscopy. Liposomes were prepared by sonication and detergent dialysis. Binding (adsorption) of radiolabeled phospholipid to synaptosomes was saturable when liposomes were in the liquid-crystalline state, were electrically neutral (egg-phosphatidylcholine), or carried increasing fractions (10:2 and 10:4 molar ratio) of negatively charged phosphatidic acid. Analysis using the Langmuir isotherm equation indicated a biphasic adsorption behavior. Adsorption increased with increasing temperature (4 degrees C and 37 degrees C). Binding was nonsaturable when liposomes were positively charged with stearylamine or composed of dimyristoylphosphatidylcholine and phosphatidylinositol (10:2 molar ratio). Due to the latter composition's solid state at 4 degrees C, temperature dependency was inverse. Electron micrographs revealed disc-shaped areas of adsorption that were free of integral membrane particles which appeared to form a condensed layer surrounding the areas of liposome adsorption. Following interaction with stearylamine-containing liposomes the vesicular structure of synaptosomes appeared largely destroyed. It is concluded that both liposome surface charge and membrane fluidity determine the extent of interaction with biological membranes. PMID- 2915599 TI - A single exposure to cocaine or immobilization stress provides extremely long lasting, selective protection against sudden cardiac death from tetracaine. AB - Exposure of rats to one injection of cocaine (35 mg/kg, i.p.) or a single four hour period of immobilization protected them from the virtually instantaneous death but not from the later, seizure-related death seen in untreated controls following administration of the local anesthetic, tetracaine, 1-4 weeks later. These data suggest that when appropriately timed, strong sympathomimetic stimulation--whether generated by an environmental stressor or a drug--can provide long-lasting protection against the sudden cardiac death potential of local anesthetics. As such, they provide a means for understanding why the incidence of sudden cardiac arrest from one such agent--cocaine itself--is not higher and suggest that an individual's stress history may play a key role in determining vulnerability to the cardiotoxic effect of this compound. PMID- 2915600 TI - Dietary linoleic acid is required for development of experimentally induced alcoholic liver injury. AB - We had previously hypothesized that linoleic acid (LA) was essential for development of alcoholic induced liver injury in our rat model. Male Wistar rats were fed a nutritionally adequate diet (25% calories as fat) with ethanol (8-17 g/kg/day). The source of fat was tallow (0.7% LA), lard (2.5% LA) or tallow supplemented with linoleic acid (2.5%). Liver damage was followed monthly by obtaining blood for alanine aminotransferase assay and liver biopsy for assessment of morphologic changes. Enzyme and histologic changes (fatty liver, necrosis and inflammation) in the tallow-linoleic acid-ethanol fed animals were more severe than in the lard-ethanol group. The tallow ethanol group did not show any evidence of liver injury. Our results strongly support our hypothesis that LA is essential for development of alcoholic liver disease in our rat model. PMID- 2915601 TI - Effect of spontaneous ingestion of ethanol on brain dopamine metabolism. AB - The effect of ethanol, either administered by gavage or voluntarily ingested, on brain dopamine (DA) metabolism was studied in alcohol-preferring and alcohol non preferring rats. In alcohol non-preferring rats ethanol administration (2 g/kg) increased 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) and reduced DA levels in the caudate nucleus and olfactory tubercle but was ineffective in the medial prefrontal cortex. In alcohol-preferring rats ethanol effect was greater than in non-preferring animals and ethanol influenced DA metabolism also in the medial prefrontal cortex. The effect of voluntary ethanol ingestion was studied in alcohol-preferring rats trained to consume their daily fluid intake within 2 hrs. Voluntary ingestion of ethanol (3.1 +/- 0.7 g/kg in 1 hr) increased DA metabolites and reduced DA levels in the caudate nucleus, olfactory tubercle and medial prefrontal cortex. The results suggest that voluntary ethanol ingestion increases the release of DA from nigro-striatal and meso-limbic DA neurons. PMID- 2915602 TI - Anti-hypoxic effect of glutathione depletors. AB - The effect of various reduced glutathione (GSH) depletors on the survival time under normobaric and hypobaric hypoxia was examined in mice. The survival time was markedly prolonged in mice treated with glutathione S-transferase substrate, 2-cyclohexene-1-one (50-100 mg/kg, ip) and phorone (100-250 mg/kg, ip). The anti hypoxic effect lasted for at least 3 hr and the maximum effect was found 0.5 hr after injection. Further, both compounds significantly elevated blood glucose levels 0.5-1 hr after treatment. The extent of the elevated blood glucose was nearly comparable to that of the mice treated with glucose (1-2 g/kg, ip), which was found to possess an anti-hypoxic effect. However, a GSH synthesis inhibitor, buthionine sulfoximine, could cause neither a prolongation of survival time of hypoxic mice nor an elevation of blood glucose. Moreover, unlike the depletion of hepatic GSH, brain GSH was markedly decreased by 2-cyclohexene-1-one and phorone, but not by buthionine sulfoximine. These findings suggest that the elevated blood glucose may involve in one of the mechanisms of the anti-hypoxic effect of 2 cyclohexene-1-one and phorone. A relationship between the anti-hypoxic effect and the depletion of brain GSH was also discussed. PMID- 2915603 TI - Homocysteinemia in rats induced by folic acid deficiency. AB - The effect of folate deficiency on homocysteine metabolism was examined in rats given a folate-deficient diet. Total homocysteine was determined in serum stored at -22 degrees C for 3 wk. All animals in the control group had more than 20 ng.ml-1 of serum folate and more than 1000 pg.ml-1 of serum cyanocobalamin throughout the experimental period. In contrast, serum folate in animals given the folate-deficient diet decreased to less than 3 ng.ml-1 after 4 wk and to less than 2 ng.ml-1 (a subnormal level) after 10 wk of the experiment while serum cyanocobalamin remained at more than 1000 pg.ml-1 throughout the experiment. In the control group, mean serum total homocysteine +/- SD was 4.04 +/- 1.07 nmol.ml 1 during the 20 wk of experiment. At the 10th wk before serum folate reached subnormal levels, the animals given the folate-deficient diet had a mean serum total homocysteine of 7.67 +/- 1.53 nmol.ml-1, demonstrating a significant increase (P less than 0.001). No further significant increase of mean serum total homocysteine concentrations was observed after serum folate became subnormal. This study demonstrated for the first time that a selective deficiency of folic acid caused a 2-4 fold increase in serum total homocysteine when serum folate was at low normal and at subnormal levels in rats. PMID- 2915604 TI - Neurotensin affects metabolism of opioid peptides, catecholamines and inositol phospholipids in bovine chromaffin cells. AB - Bovine adrenal medullary cells released significant amounts of opioid pentapeptides Met- and Leu-enkephalin and catecholamines, when stimulated by neurotensin (NT). Maximal release induced by this peptide was about 40-50% of that seen after nicotinic activation of cholinergic receptors. Dose-response curves for neurotensin-induced secretion revealed an EC50 of 1x10(-6)M, thereby being in the range of that for acetylcholine or nicotine. Secretory effects were dependent on extracellular Ca++ and impaired by the Ca++ channel blocker D 600. Moreover NT produced an increase in opioid peptide cell content after 48 and 72 hrs of incubation. Besides affecting opioid peptide metabolism, NT significantly produced accumulation of inositol- 1-phosphates (IP1), the significance of which remains to be clarified in the observed metabolic effects. PMID- 2915605 TI - Combined H1 and H2 receptor blockade attenuates the cardiovascular effects of high dose atracurium in rabbits. AB - Large doses of atracurium (1.5 mg/kg) (six times the ED95) have been reported to provide adequate conditions for rapid sequence endotracheal intubation within 60 seconds in humans. However, this dose can result in significant histamine release and systemic hypotension. We therefore studied the efficacy of histamine receptor blockade in attenuating this response. Four groups of five rabbits were pretreated as follows: Group I--control, Group II--H1 blockade (1 mg/kg diphenhydramine), Group III--H2 blockade (cimetidine 4 mg/kg), and Group IV--H1 and H2 blockade (diphenhydramine 1 mg/kg and cimetidine 4 mg/kg). All rabbits were anesthetized and then 1.8 mg/kg (six times the rabbit ED95) atracurium was administered. Group I rabbits experienced a decrease in MAP of 12.2 mmHg after one minute, a change that was significantly greater than Group IV in which MAP decreased by 0.8 mmHg (p less than 0.001). H1 or H2 receptor blockade alone was associated with intermediate changes in MAP not significantly different from control. We conclude that combined H1 and H2 receptor blockade attenuates the cardiovascular effects associated with large doses of atracurium in the rabbit and that this combination of antagonist drugs might have similar effectiveness in humans. PMID- 2915606 TI - The management of uncommon malignancies of the breast (Part II) PMID- 2915607 TI - A patient with biliary tract obstruction and AIDS. PMID- 2915608 TI - Independent status for hospital medical staffs: no cause for antitrust alarm. AB - In recent years, there has been a growing controversy surrounding the issue of so called "independent status" for hospital physician staffs. During the late 1970s and early 1980s, some articles advanced the theory that any conduct creating the appearance of an independent status for the hospital staff separate from that of the hospital could generate the environment for an antitrust action. These early theories, however, failed to fully appreciate the basic nature of antitrust law and the changing role of the hospital medical staff. Indeed, the changing nature of the hospital medical staff and the current application of antitrust law strongly indicate the early theories are misplaced and the "independent status" of the hospital medical staff does not create cause for antitrust alarm. PMID- 2915609 TI - Triplicate prescription: an idea whose time has yet to come. AB - A coalition of Maryland state officials and agencies is considering the introduction of legislation that would enact a triplication prescription program, a concept that dates back almost a half century. To date, only eight states have adopted such legislation, and since 1964, at least sixteen other states have thoroughly examined the concept and rejected it. PMID- 2915610 TI - Analysis of an incompetence case. AB - In recent months various Maryland health occupational boards have come under fire for their response to complaints against particular licensees. While this criticism may or may not be justified, the issue of how to proceed against incompetent licensees is a common problem nationwide. In Maryland's explosion of cases involving malpractice, far more licensees are disciplined for offenses relating to drugs or sex than for incompetence. An approach to make the boards more responsive to the problem of the incompetent licensee is presented. PMID- 2915611 TI - State regulation of physician dispensing. PMID- 2915612 TI - Practice computerization: hints and suggestions. AB - Roughly 13 percent of United States physicians in private practice own microcomputers and use them to manage their offices. This is an increase of nearly 8 percent in just five years. At this rate, 20 percent of physicians will own computers by the end of the decade. The consensus is that the pressures of costs, regulations, and competition render a simple manual ledger ineffective. A ledger cannot provide an alert to recall a patient, summarize financial data, nor produce medical reports for regulatory agencies. Consequently, to remain successful in the 90s, more physicians are turning to microcomputers to "manage" their practices more efficiently. PMID- 2915613 TI - Health promotion and disease prevention in the care of older adults: preventive practice in primary care. AB - Prevention is an important and appropriate component of the primary care of older adults. Office-based approaches to prevention include routinely scheduled examinations for health maintenance and case finding for early disease and disability during visits scheduled for other purposes. The primary care clinician is the optimal person for effective preventive intervention in patients 65 years and older. The spectrum of preventive activities ranges from screening by history taking, physical examination, and laboratory tests to intervention by counseling and therapeutic intervention. Unfortunately, substantial barriers exist to widespread incorporation of preventive practices into primary care, including the need for information and the low level of third-party reimbursement in this area. PMID- 2915614 TI - Health maintenance issues of the elderly. Nutrition. AB - Although we are on steep learning curve as far as the exact relationship between nutrition and disease prevention is concerned, evidence is accumulating on the role of body mass index and mortality, protein deficiency and decreased ability to fight infection, effect of fiber intake on cholesterol and glucose metabolism, hyperlipidemia and atherosclerosis, and inadequate calcium intake in osteoporosis. Screening for nutritional disorders includes identifying those with risk factors of being female, black, poor, or institutionalized. Evidence of weight change, dietary idiosyncracies, nutrient deficiency, and laboratory tests can be helpful. Treatment should be tailored to the individual and be specific for suspected deficiencies. Attention to calories, protein, and calcium are paramount. PMID- 2915615 TI - Health maintenance issues of the elderly. Oral health. AB - The risk for the most serious oral disease, oral cancer, increases with age as does the prevalence of other oral soft tissue diseases. Tooth loss is not part of normal aging. As more elderly retain their natural dentition, they are at continued risk for tooth-related diseases such as caries and periodontal disease. Preventive dental programs, including an oral exam as part of the physical examination, will be indicated for adults. PMID- 2915616 TI - Health maintenance issues of the elderly. Sleep. AB - Our understanding of the effect of aging on normal sleep and specific sleep disorders in the elderly has increased significantly in the last decade. Sleep complaints and the use of sedative hypnotics in the elderly are now more frequent than in younger patients. It is important in the management of elderly patients to determine whether a formal laboratory evaluation of a patient needs to be undertaken to diagnose a specific sleep disorder prior to initiating drug therapy for nonspecific complaints of difficulty with sleep. PMID- 2915617 TI - Health maintenance issues of the elderly. Exercise. AB - If ever there an antidote to the decline associated with aging, it might be physical exercise. Older people who exercise regularly tent to be those at whom we marvel: they live longer, more vigorous, independent lives. Exercise has provided them with keys to a better quality of life and cardiovascular fitness, strengthened muscles, a well-functioning nervous system, good mental health, and improved functional capacity. PMID- 2915618 TI - Health maintenance issues of the elderly. Vision: age-related macular degeneration. AB - Age-related macular degeneration (AMD) is the leading cause of irreversible severe visual loss in the United States among persons over 50 years old. The majority of patients who develop severe visual loss from AMD have exudative disease. Treatment for AMD has been shown to be effective for only a small portion of patients who have well-defined choroidal neovascular membranes (CNVM) outside the foveal center. Even when successfully treated, severe visual loss is postponed for only about 18 months because of the high rate of recurrent CNVMs extending through the fovea. Presently, low-vision aids are the only treatment available for the majority of patients with exudative disease. PMID- 2915619 TI - Health maintenance issues of the elderly. Hearing. AB - Estimates of the prevalence of hearing impairment individuals over 65 years old are on the order of 30 percent. Although the psychosocial consequences of hearing impairment may be profound, less than 20 percent of hearing-impaired adults use hearing aids to compensate for their hearing loss. Primary care physicians play a vital role in identifying hearing impairment in the elderly and in assisting the older adult in obtaining rehabilitative services, including hearing aids. Screening tools, which are inexpensive, simple to use, and valid, are available for use in the primary care setting. PMID- 2915620 TI - Health maintenance of the elderly. Sexuality. AB - Empirical research, clinical experience, and greater sophistication about the interaction of social, psychological, and biological factors have produced marked changes in the appreciation of the importance of sexuality in older persons. An earlier view linking sex exclusively with reproductive function has given way to a holistic view of sex as vital to self-concept, the maintenance of healthy interpersonal relationships, and a sense of integrity. Older adults often have difficulty communicating sexual problems, concerns, and questions because of their conflicting attitudes and perceptions. Sexual problems often are presented covertly, expressed in vague terms, or masked by embarrassment. Physicians need to be aware of the possibility of covert sexual dysfunctions, clear about their own attitudes and expectations to avoid stereotyping the elderly, and knowledgeable about pharmacological, organic, and psychosocial bases of sexual problems in older patients. PMID- 2915621 TI - Health maintenance issues of the elderly. Immunization. AB - The elderly are frequently underimmunized against vaccine-preventable infectious diseases. Comprehensive immunization of patients for vaccine-preventable diseases represent a major challenge for physicians treating the elderly. The healthy elderly should be specifically targeted since they are most likely to mount an appropriate immune response to the vaccine. Programs to identify inadequately immunized patients should be widely implemented. PMID- 2915623 TI - Physicians and suicidal patients. PMID- 2915622 TI - Planning for medical decision making: living wills and durable powers of attorney. AB - The enactment of living will and durable power of attorney statutes in most states, including Maryland, provide individuals with a mechanism for setting forth their preferences for medical treatment in the event of their inability to make treatment decisions on their own behalf. Although still under used, these mechanisms are becoming more common, and physicians will be confronting them more frequently. The following overview of the Maryland Life Sustaining Procedures Act and the Durable Power of Attorney Act and discussion of their advantages and limitations is from the perspective of patients and their physicians. PMID- 2915624 TI - Court authorizes parents to withdraw life support. PMID- 2915625 TI - Health claims on food labels. PMID- 2915626 TI - Renal nerves. PMID- 2915627 TI - Pregnancy residency. Are the demands too great? PMID- 2915629 TI - The issues behind "living will" legislation. PMID- 2915630 TI - Tax considerations for physicians. PMID- 2915628 TI - Pericardial effusion complicating acute myocardial infarction. AB - The acute fibrinous pericarditis that complicates acute myocardial infarction is usually of no functional significance. Uncommonly, hemorrhagic effusion may compound this process. In the case reported here, the pericardial aspect of acute lateral myocardial infarction dominated the clinical picture, thus posing a diagnostic problem. This phase of the disease stimulates us to place it on record. PMID- 2915631 TI - AIDS grant for "U". PMID- 2915632 TI - HIV-infected hemophiliacs. PMID- 2915633 TI - New age woman. Interview by Richard L. Reece. PMID- 2915634 TI - Practicing medicine in the quiet zone. Interview by Richard L. Reece. PMID- 2915635 TI - A window on the neonate's brain. PMID- 2915636 TI - Developmental care of the preterm infant. AB - The infant, both term and preterm, has remarkable abilities for interacting with the environment. Infant care has changed as we have learned more about the infant's capabilities and needs. Preterm infants experience both sensory overload and sensory deprivation in the typical NICU. In the past, care models based on minimal handling or infant stimulation were developed to meet the needs of the NICU patients. Current knowledge has led to the development of comprehensive "developmental intervention" programs, which combine the best of the two previous models and provide optimal developmental care for the preterm or at-risk infant. Parental involvement in the developmental plan is essential. The neonatal nurse can have a positive influence on the preterm infant's outcome by staying informed of current developmental findings, implementing techniques to minimize detrimental stimuli, and providing appropriate stimuli. The most powerful influence on the outcome is support and education of the parents. PMID- 2915637 TI - A makeshift mini-bottle: accurate small volume fluid or oral medication administration to infants. PMID- 2915638 TI - Cardiac function and the neonatal EKG. Part I: Introduction to neonatal EKGs. PMID- 2915639 TI - RCTs. PMID- 2915640 TI - Ethics: a beginning. PMID- 2915641 TI - Digoxin. PMID- 2915642 TI - Pneumonia and influenza mortality--United States, 1988-89 season. PMID- 2915643 TI - Mumps--United States, 1985-1988. PMID- 2915644 TI - Messenger ribonucleic acid encoding an apparent isoform of phosphorylase kinase catalytic subunit is abundant in the adult testis. AB - The complete amino acid sequence for a novel member of the protein kinase family was deduced from the nucleotide sequence of a cloned human cDNA. This putative protein kinase, given the preliminary designation "PSK-C3," is similar in primary structure to phosphorylase kinase catalytic subunit (PhK-gamma) isolated from rabbit skeletal muscle. The level of similarity does not appear sufficient, however, to suggest that PSK-C3 represents the human homolog of skeletal muscle PhK-gamma. Rather, it seems likely that PSK-C3 is a novel PhK-gamma isoform. From a cross-species Northern hybridization experiment using adult rat tissue RNA, a transcript homologous to PSK-C3 was found to be abundant in the testis but could not be detected in any of 12 other tissues tested, including skeletal muscle, liver, and ovary. Increasing levels of PSK-C3 mRNA in the testis correlate with postnatal testicular development, suggesting possible hormonal regulation of gene transcription. Energy released by glycogeneolysis in the testis may help fuel the process of spermatogenesis. PMID- 2915645 TI - A neuroendocrine peptide derived from the amino-terminal half of rat procalcitonin. AB - The sequence of rat procalcitonin reveals that calcitonin is located within the precursor's midregion, flanked by two potential polybasic cleavage sites that separate it from amino- and carboxyl-terminal domains. Cleavage at the polybasic sites during precursor processing to generate the 32-residue calcitonin should also generate 57- and 16-residue peptides from the amino- and carboxyl-terminal flanking regions. The carboxyl-terminal flanking hexadecapeptide and its coordinate secretion from C cells with calcitonin have been previously reported. In the present study we have focused on the predicted 57-residue amino-terminal procalcitonin cleavage peptide (N-proCT). We raised antisera to synthetic peptides homologous to the carboxyl- and amino-terminal regions of the putative 57-amino-acid N-proCT and screened calcitonin-rich neoplastic and nonneoplastic C cells for these two immunoreactivities. A single species of 7.4 kilodaltons detected in C cells by gel filtration and reversed-phase HPLC analyses accounts for most of the carboxyl- and amino-terminal immunoreactivities and possesses the biochemical and biological features predicted for N-proCT. When C cell hyperplasia is induced by a high fat diet, thyroidal levels of calcitonin and N proCT increase in parallel. In neoplastic C cell cultures, N-proCT and calcitonin concentrations are nearly equimolar in both cellular extracts and basal medium; dexamethasone increases both the cellular and secreted concentration of these peptides. Basal and dexamethasone-treated cultures show calcium-dependent, parallel secretion of N-proCT and calcitonin. Thus, the 57-residue N-proCT predicted from analysis of the procalcitonin sequence is a secretory peptide that appears to be present in equimolar amounts and coordinately regulated with calcitonin in vivo and in vitro. PMID- 2915646 TI - Chicken calmodulin promoter activity in proliferating and differentiated cells. AB - A 1218-base pair (bp) portion of the chicken calmodulin promoter was sequenced and assayed for promoter activity. This portion of the promoter was found sufficient to produce accurate transcriptional initiation. The promoter sequence was GC rich, particularly in the 700 bp region 5' to the cap site. Eight plasmids were prepared containing the first calmodulin exon and 30-1218 bp of the promoter, ligated to the reporter gene chloramphenicol acetyl transferase. In chicken embryonic fibroblasts and proliferating BC3H-1 cells promoter activity increased progressively with increasing promoter length up to 617 bp. Extension of the promoter beyond 617 bp inhibited expression, as did sequences within the first calmodulin exon. In BC3H-1 cells differentiation was found to reduce calmodulin mRNA levels approximately 3-fold. Activity of the calmodulin promoter constructs also decreased by a similar extent with differentiation. Sequences up to 234 bp 5' to the calmodulin cap site were markedly less effective in elevating chloramphenicol acetyl transferase activity in differentiated BC3H-1 cells than in proliferating cells and may account for the lower overall activity of the calmodulin promoter in these cells. Within this region several sequences were identified, including an extensive homology to the rat calmodulin I gene promoter that could be significant in regulation of calmodulin expression. PMID- 2915647 TI - Hormonal regulation of estrogen receptor messenger ribonucleic acid in T47Dco and MCF-7 breast cancer cells. AB - Using a combination of hormone-binding assays, immunologic techniques, and mRNA hybridizations we have measured the estrogen receptor (ER) content and studied the hormonal regulation of ER mRNA in one estrogen responsive and one estrogen unresponsive breast cancer cell line, MCF-7 and T47Dco, respectively. Estradiol binding could be detected in cytosol from MCF-7 cells but not in T47Dco cells. However, when measured by an enzyme-linked immunosorbent assay, T47Dco cells were found to contain approximately 15 fmol ER/mg cytosolic protein or 10% of the ER content in MCF-7 cells. Immunologically reactive ER in T47Dco cells was indistinguishable in size (approximately equal to 68 KD) from the ER in MCF-7 cells, as shown by Western blotting using a monoclonal antihuman ER antibody. Quantification of ER mRNA in MCF-7 and T47Dco cells indicated that T47Dco cells contained approximately 50% of the ER mRNA levels found in MCF-7 cells. This basal level of ER mRNA in T47Dco cells was not decreased by estradiol treatment, as opposed to in MCF-7 cells where estradiol caused 40-60% decrease in the ER mRNA expression. Also, estradiol did not increase the progesterone receptor (PR) mRNA levels in T47Dco cells whereas in MCF-7 cells an approximately 5-fold increase of the PR mRNA levels occurred after estradiol treatment. However, incubation of the cells with the synthetic progestin R5020 decreased the ER mRNA levels to approximately the same degree in both cell lines. In conclusion, we have shown that estrogen down-regulates ER mRNA and up-regulates PR mRNA in MCF-7 cells. Neither of these estrogenic effects were seen in T47Dco cells. It appears that the steroid-resistance in T47Dco cells does not occur as a consequence of a complete absence of ER mRNA or protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2915648 TI - Identification and estrogen induction of two estrogen receptors (ER) messenger ribonucleic acids in the rainbow trout liver: sequence homology with other ERs. AB - The estrogen-binding region of the cDNA for chicken ER reveals a mRNA of 3.5 kilobases (kb) in rainbow trout liver. The level of this messenger, which is very low in the liver of naive male animals, can be increased by estrogen stimulation. With this chicken probe, we have isolated a clone from a lambda gt10 trout liver cDNA library. The partial cDNA sequence, which encompasses most of the coding region, shows two domains of striking amino acid homology with human, avian, and Xenopus estrogen receptors (ERs) (DNA binding region: 90%, Hormone binding region: 60%). With this specific probe rainbow trout ER, we detected another messenger (4.5 kb) that is less expressed than the 3.5 kb messenger. The kinetics of stimulation of the two messengers is compared with the kinetics of accumulation of vitellogenin mRNA after E2 administration. This report constitutes the first identification of ER mRNA from a fish. PMID- 2915649 TI - High level, cell-specific expression of ornithine decarboxylase transcripts in rat genitourinary tissues. AB - We evaluated transcript levels for the rate-limiting enzyme in polyamine biosynthesis, ornithine decarboxylase (ODC), in rat tissues by Northern blotting and in situ hybridization histochemistry, using a rat cDNA probe. ODC transcripts were expressed at a high level, relative to levels in other tissues, in the kidney and testis of the adult rat; maximal levels of transcripts in these tissues occurred after sexual maturation had taken place, i.e. between 20 and 150 days of age. In situ hybridization histochemistry revealed high level expression in the kidney, testis, prostate, and seminal vesicles of the male rat; this high level expression was limited to certain cell types: kidney, S3 cells of the proximal convoluted tubule; prostate and seminal vesicles, glandular or luminal epithelial cells; and testis, early spermatogenic cells. High level expression of ODC mRNA disappeared from the prostate and seminal vesicle epithelial cells after castration and reappeared with testosterone treatment; in contrast, levels of kidney ODC mRNA were essentially unchanged by castration and were similar in male and female adult rats. We conclude that high level ODC mRNA expression occurs in specific cell types in the adult rat, where it appears to be regulated by both androgen-dependent and independent mechanisms. PMID- 2915650 TI - 1,25-Dihydroxyvitamin D3 interaction with dexamethasone and retinoic acid: effects on procollagen messenger ribonucleic acid levels in rat osteoblast-like cells. AB - We previously have reported that 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], dexamethasone, and retinoic acid inhibit collagen synthesis in rat osteoblast like cell primary cultures. We also have found that dexamethasone increases 1,25 (OH)2D3 receptor levels in these cells. Furthermore, this increase in 1,25 (OH)2D3 receptor level is paralleled by an enhanced inhibition of collagen synthesis when dexamethasone and 1,25-(OH)2D3 are used in combination. In contrast, retinoic acid at high doses decreases 1,25-(OH)2D3 receptor level in rat osteoblast-like cells and attenuates 1,25-(OH)2D3 inhibition of collagen synthesis. In the present study, we have used a [32P]cDNA probe for rat pro alpha 1 (I) to determine if these osteotropic agents act by modulating steady state procollagen mRNA levels. Hybridization with a [32P]cDNA probe for human actin was used as a control. We find that the steady state levels of procollagen mRNA are decreased in all cases, while there are negligible changes in actin mRNA levels. Dexamethasone, at the low dose of 13 nM, acts synergistically with 1,25-(OH)2D3 in decreasing procollagen mRNA levels. The effects of retinoic acid and 1,25 (OH)2D3 are additive at low doses (13 and 130 nM); however, at a high dose of retinoic acid (1.3 microM), combined treatment with 1,25-(OH)2D3 does not reduce procollagen mRNA levels beyond the decrease due to retinoic acid alone. The reduction in procollagen mRNA level after each of these treatments falls in the same range as inhibition of collagen synthesis measured at the protein level. These data suggest that the synthesis of collagen under these treatments is controlled primarily through modulation of steady state procollagen mRNA levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2915651 TI - Efficacy of adjuvant chemotherapy in high-risk node-negative breast cancer. An intergroup study. AB - We randomly assigned 536 women who had undergone either a modified radical mastectomy or a total mastectomy with low axillary-node dissection for potentially curable breast carcinoma to receive adjuvant chemotherapy or no treatment observation. The patients were considered at high risk for recurrence because they had either an estrogen-receptor-negative tumor of any size or an estrogen-receptor-positive tumor at least 3 cm in diameter with no histopathological evidence of axillary-node involvement. The chemotherapy consisted of six four-week cycles of cyclophosphamide (100 mg per square meter of body-surface area orally on days 1 through 14), methotrexate (40 mg per square meter intravenously on days 1 and 8), fluorouracil (600 mg per square meter intravenously on days 1 and 8), and prednisone (40 mg per square meter orally on days 1 through 14). Treatments were balanced with respect to patients' characteristics. The analysis included 406 eligible patients who were entered in the study before October 1, 1987. The overall disease-free survival among patients treated with the four-drug regimen was 84 percent, as compared with 69 percent for the control group, at a median follow-up of three years (P = 0.0001). A treatment benefit was also observed in premenopausal and postmenopausal patients as well as in patients with estrogen-receptor-positive or with estrogen receptor-negative tumors. Severe or life-threatening hematologic toxicity was encountered in 33 percent of the treated patients, with one death. Our results indicate that adjuvant chemotherapy with six cycles of cyclophosphamide, methotrexate, fluorouracil, and prednisone is effective in improving three-year disease-free survival among high-risk patients with axillary-node-negative, operable breast cancer. An analysis of the effect of treatment on survival awaits a longer follow-up. PMID- 2915652 TI - Radiologic contributions to the investigation and prosecution of cases of fatal infant abuse. AB - In 1984 we started a two-year program in Worcester (Mass.) and Boston to provide additional radiologic data for the medical investigation of suspected fatal infant abuse. During that period the investigation of 12 cases of unexplained infant death included the review of complete radiographic skeletal surveys by a pediatric radiologist. Autopsies were supplemented with resection, high-detail radiography, and histologic study of all non-cranial sites of suspected osseous injury. Thirty-four bony injuries were noted, including 12 acute and 16 healing fractures of the long-bone metaphyses and posterior-rib arcs in patterns indicative of infant abuse. The investigations determined that there were eight cases of abuse, two accidental deaths, and two natural deaths (sudden infant death syndrome). At this writing, the radiologic and osseous histologic studies appear to have influenced the determination of the manner of death in six of the eight cases of abuse and the criminal prosecution in four of the five convictions. These findings suggest that a thorough postmortem radiologic evaluation followed by selected histologic studies can have an impact on the investigation and prosecution of cases of fatal infant abuse. PMID- 2915653 TI - Selective delivery of an acardiac, acephalic twin. PMID- 2915654 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 8-1989. A 46-year-old woman with progressive dementia. PMID- 2915655 TI - Adjuvant therapy of node-negative breast cancer. PMID- 2915656 TI - Breast cancer therapy: exercising all our options. PMID- 2915657 TI - Advances and retreats in the protection of children. PMID- 2915658 TI - Resource-based relative-value scale for physicians' reimbursement. PMID- 2915659 TI - High monounsaturated fat diet for non-insulin-dependent diabetes mellitus. PMID- 2915660 TI - Ventricular fibrillation during antiarrhythmic drug therapy. PMID- 2915661 TI - Epidemic listeriosis. PMID- 2915663 TI - Abbreviated breakthrough. PMID- 2915662 TI - More on the costs of beta-lactam antibiotics. PMID- 2915664 TI - A selective medical school admissions policy to increase the number of family physicians. PMID- 2915665 TI - A prospective study of the risk of tuberculosis among intravenous drug users with human immunodeficiency virus infection. AB - To determine the risk of active tuberculosis associated with human immunodeficiency virus (HIV) infection, we prospectively studied 520 intravenous drug users enrolled in a methadone-maintenance program. Tuberculin skin testing and testing for HIV antibody were performed in all subjects. Forty-nine of 217 HIV-seropositive subjects (23 percent) and 62 of 303 HIV-seronegative subjects (20 percent) had a positive response to skin testing with purified protein derivative (PPD) tuberculin before entry into the study. The rates of conversion from a negative to a positive PPD test were similar for seropositive subjects (15 of 131; 11 percent) and seronegative subjects (26 of 202; 13 percent) who were retested during the follow-up period (mean, 22 months). Active tuberculosis developed in eight of the HIV-seropositive subjects (4 percent) and none of the seronegative subjects during the study period (P less than 0.002). Seven of the eight cases of tuberculosis occurred in HIV-seropositive subjects with a prior positive PPD test (7.9 cases per 100 person-years, as compared with 0.3 case per 100 person-years among seropositive subjects without a prior positive PPD test; rate ratio, 24.0; P less than 0.0001). We conclude that, although the prevalence and incidence of tuberculous infection were similar for both HIV-seropositive and HIV-seronegative intravenous drug users, the risk of active tuberculosis was elevated only for seropositive subjects. These data also suggest that in HIV infected persons tuberculosis most often results from the reactivation of latent tuberculous infection; our results lend support to recommendations for the aggressive use of chemoprophylaxis against tuberculosis in patients with HIV infection and a positive PPD test. PMID- 2915666 TI - Reduced bone mass in daughters of women with osteoporosis. AB - To determine whether premenopausal daughters of women with postmenopausal osteoporosis have lower bone mass than other women of the same age, we measured the bone mineral content of the lumbar spine and femoral neck and midshaft, using dual-photon absorptiometry, in 25 postmenopausal women with osteoporotic compression fractures and in 32 of their premenopausal daughters; we then compared the results with those in normal controls. As compared with normal postmenopausal women, women with osteoporosis had lower bone mineral content in the lumbar spine, femoral neck, and femoral midshaft by 33, 24, and 15 percent, respectively (P less than 0.001 for each comparison by the one-tailed t-test). As compared with normal premenopausal women, the daughters of women with osteoporosis had lower bone mineral content at these sites by 7, 5, and 3 percent, respectively (P = 0.03, 0.07, and 0.15, respectively, by the one-tailed t-test). In terms of a standardized score, we calculated that the mean (+/- SEM) relative deficits in bone mineral content in the daughters of women with osteoporosis were 58 +/- 18 percent (lumbar spine) and 34 +/- 16 percent (femoral neck) of the relative deficits in their mothers. We conclude that daughters of women with osteoporosis have reduced bone mass in the lumbar spine and perhaps in the femoral neck; this reduction in bone mass may put them at increased risk for fractures. We also conclude that postmenopausal osteoporosis may result partly from a relatively low peak bone mass rather than from excessive loss of bone. PMID- 2915667 TI - Race and therapeutic drug response. PMID- 2915668 TI - American medicine at the crossroads: signs from Canada. PMID- 2915669 TI - Indoor radon and lung cancer. PMID- 2915670 TI - Failure of zidovudine to maintain remission in patients with AIDS. PMID- 2915671 TI - Alcohol consumption and withdrawal in new-onset seizures. PMID- 2915672 TI - Acid-base abnormalities in cardiopulmonary arrest: varying patterns in different locations in the hospital. PMID- 2915673 TI - Brachial plexus injury due to vest restraints. PMID- 2915674 TI - Abrasive shirts may contribute to herpes gladiatorum among wrestlers. PMID- 2915675 TI - Actinomycotic tonsillitis with expectoration of sulfur granules. PMID- 2915676 TI - Cigarette export promotion by the American government. PMID- 2915677 TI - Outcomes management: a technology of patient experience. PMID- 2915678 TI - Managing the third-party payers. PMID- 2915679 TI - Japan's science budget expands. PMID- 2915680 TI - West German biochemistry institute set ablaze by "viruses". PMID- 2915681 TI - BMA scorns loans. PMID- 2915682 TI - European molecular biology laboratory in search of a director. PMID- 2915683 TI - Rifkin tries to block human gene transfer experiment. PMID- 2915684 TI - Genetics of schizophrenia. PMID- 2915685 TI - More ways with neural networks. PMID- 2915686 TI - Cognitive control of movement. PMID- 2915687 TI - Lethality of 'killer' bee stings. PMID- 2915688 TI - Single-strand RNA. PMID- 2915689 TI - Taxonomic stability. PMID- 2915690 TI - A novel eye in 'eyeless' shrimp from hydrothermal vents of the Mid-Atlantic Ridge. AB - Rimicaris exoculata is a shrimp that swarms over high-temperature (350 degrees C) sulphide chimneys at Mid-Atlantic Ridge hydrothermal fields (3,600 m). This shrimp lacks an externally differentiated eye, having instead a pair of large organs within the cephalothorax immediately beneath the dorsal surface of the transparent carapace, connected by large nerve tracts to the supraesophageal ganglion. These organs contain a visual pigment with an absorption spectrum characteristic of rhodopsin. Ultrastructural evidence for degraded rhabdomeral material suggests the presence of photoreceptors. No image-forming optics are associated with the organs. We interpret these organs as being eyes adapted for detection of low-level illumination and suggest that they evolved in response to a source of radiation associated with the environment of hydrothermal vents. PMID- 2915691 TI - Segment-specific expression of a zinc-finger gene in the developing nervous system of the mouse. AB - The process of segmentation, in which repeated homologous structures are generated along the anterior-posterior axis of the embryo is a widespread mechanism in animal development. In vertebrates, segmentation is most apparent in the somites and the peripheral nervous system, but the existence of repetitive bulges, termed neuromeres, in the early neural epithelium of vertebrates suggests that the CNS may also be segmented. Consistent with this, cranial ganglia and certain neurons are associated with specific hindbrain neuromeres. Here, we report that Krox-20, a zinc-finger gene, is expressed in two alternate neuromeres in the mouse early hindbrain. This pattern subsequently decays and Krox-20 is transiently expressed in specific hindbrain nuclei. In addition, Krox-20 is expressed in early neural crest cells, and then in the neural crest-derived boundary caps, glial components of the cranial and spinal ganglia. The demonstration that neuromeres are domains of gene expression provides molecular evidence for the segmentation of the CNS. PMID- 2915692 TI - Aminoacylation of RNA minihelices with alanine. AB - The genetic code is determined by both the specificity of the triplet anticodon of tRNAs for codons in mRNAs and the specificity with which tRNAs are charged with amino acids. The latter depends on interactions between tRNAs and their charging enzymes, and an advance in understanding such interactions was provided recently by the demonstration that a major determinant of the identity of alanine tRNA is located in the amino-acid acceptor helix. Multiple substitutions in many distinct parts of the molecule do not prevent aminoacylation with alanine. Substitution of the G3.U70 base pair with G3.C70 or A3.U70 in the acceptor helix prevents aminoacylation in vivo and in vitro, however, and the introduction of this base pair into tRNA(Cys) (ref. 1) or tRNA(Phe) (refs 1, 2) enables both to accept alanine. The importance of a single base pair in the acceptor helix and the results of recent footprinting experiments promoted us to investigate the possibility that a minihelix, composed only of the amino-acid acceptor-T psi C helix, could be a substrate for alanine tRNA synthetase. We show here that a synthetic hairpin minihelix can be enzymatically aminoacylated with alanine. Alanine incorporation requires a single G.U base pair, and occurs in helices that otherwise differ significantly in sequence. Aminoacylation can be achieved with only seven base pairs in the helix. PMID- 2915693 TI - Long-range structural changes in proteinase K triggered by calcium ion removal. AB - The X-ray crystal structure of the subtilisin-type enzyme proteinase K at 1.5 A resolution shows that is has two binding sites for Ca2+. Scatchard analysis indicates that one Ca2+ binds tightly, with pK 7.6 x 10(-8) M-1, and the other only weakly. Although Ca2+ is not directly involved in the catalytic mechanism and is 16.6 A away from the alpha-carbon atoms of the catalytic triad Asp 39-His 69-Ser 224, the activity of proteinase K towards the synthetic substrate succinyl Ala-Ala-Ala-p-nitroanilide drops slowly to approximately 20% of its original value when it is depleted of Ca2+. This is not due to autolysis of the enzyme. The X-ray crystal structure of Ca2+-free proteinase K shows that removal of Ca2+ from the tight binding site triggers a concerted domino-like movement of five peripheral loops and of two alpha-helices. At a distance of 25 A from this calcium-binding site, the geometry of both the secondary substrate binding site and of the catalytic triad is affected by this movement thereby reducing the activity of the enzyme. PMID- 2915694 TI - Advances in two-dimensional electrophoresis. AB - New developments in the first dimension step of two-dimensional electrophoresis have expanded the utility of the technique in cell and molecular biology. PMID- 2915695 TI - Paying the price of health care. PMID- 2915696 TI - NIH report not the final word on Baltimore case. PMID- 2915697 TI - Children infect mothers in AIDS outbreak at a Soviet hospital. PMID- 2915699 TI - Mutations and plagiarisms. PMID- 2915698 TI - Investigation into Tajikistan earthquake. PMID- 2915700 TI - Research, misconduct and Congress. PMID- 2915701 TI - More insect eating. PMID- 2915702 TI - Lead contamination. PMID- 2915703 TI - Superfamily expands. PMID- 2915704 TI - A parallel algorithm for real-time computation of optical flow. AB - The precise management of two-dimensional field of velocities from time-varying two-dimensional images is impossible in general. It is, however, possible to compute suitable 'optical flows' that are qualitatively similar to the velocity field in most cases. We describe a simple, parallel algorithm that computes an optical flow from sequences of real images, which is consistent with human psychophysics and suggests plausible physiological models. In particular, our algorithm runs on a Connection Machine supercomputer in close-to-real time. It shows several of the same 'illusions' that are perceived by humans. A natural physiological implementation of the model is consistent with data from cortical areas V1 and MT. PMID- 2915705 TI - Intrinsic differences in the growth rate of early nerve fibres related to target distance. AB - Target field innervation in the developing vertebrate nervous system coincides with the onset of important trophic interactions. Two factors that determine the timing of this event are the distance axons have to grow to reach their targets, which are known to vary, and the rate at which they grow. There have been few studies of axonal growth rate at this stage of development and no comparative study of the relationship between growth rate and target distance. Embryonic chick cranial sensory neurons are located in discrete ganglia and the distance axons have to grow to reach their targets is different for each ganglion, ranging from several hundred to several thousand microns. Here, I show that these neurons differ in their in vivo growth rates; neurons with more distant targets growing faster. In vitro, single isolated neurons from each of these populations grow at a similar rate to that observed in vivo, indicating that growth rate is an intrinsically determined property of neurons before they reach their targets. PMID- 2915706 TI - Thymic cortical epithelial cells can present self-antigens in vivo. AB - Antigens present during neonatal life are recognized as self and individuals are tolerant to these antigens. In normal individuals T cells are tolerant to most self proteins but we still know little of the mechanism(s) by which tolerance is established. A requisite part of the current negative selection model of self tolerance is the expression of self proteins complexed with major histocompatibility complex molecules in the thymus. As MHC proteins bind antigens and present them to the receptor on the antigen-specific T cell, then for tolerance to self to occur, it is possible that each self protein must be processed and presented by an MHC molecule. As a result of the development of a unique T-cell hybrid reactive to the self protein murine haemoglobin, we have shown that in normal animals this self protein is continuously processed and potentially presented in an MHC-restricted manner. Here we show that self haemoglobin is being processed and presented by thymic antigen-presenting cells as early as gestational day 14. We also demonstrate that three types of thymic stromal cells, namely macrophages, dendritic cells and cortical epithelial cells, can present the haemoglobin self antigen in vivo. This surprising presentation of a self antigen by thymic cortical epithelial cells implies that they could be involved in T-cell development and negative selection. PMID- 2915707 TI - Localization of muscle gene products in nuclear domains. AB - The localization of gene products is central to the development of cell polarity and pattern specification during embryogenesis. To monitor the distribution of gene products encoded by different nuclei in the same cell in tissue culture, we fused cells of different species to form multinucleated non-dividing heterokaryons. In previous fusion studies, cell-surface antigens and organelles contributed by disparate cell types intermixed within minutes. Using heterokaryons produced with differentiated muscle cells, we demonstrate here that a muscle membrane component, the Golgi apparatus mediating its transport, and a sarcomeric myosin heavy chain are localized in the vicinity of the nuclei responsible for their synthesis. These results provide direct evidence that products (organelle, membrane and structural proteins) derived from individual nuclei can remain localized in myotubes, a finding with implications both for neuromuscular synapse formation and for the carrier state of Duchenne muscular dystrophy. PMID- 2915708 TI - A hard day's knight. Zinc phosphide poisoning. PMID- 2915709 TI - Heart disease. PMID- 2915710 TI - On library services in North Carolina. PMID- 2915711 TI - The vexing prognosis of unexplained syncope (CT and Holter negative). A community hospital study. PMID- 2915712 TI - [The third revolution: accountability]. PMID- 2915713 TI - [Medicine and language]. PMID- 2915714 TI - [Resection arthroplasty of the metacarpophalangeal joints for rheumatoid arthritis; a follow-up study]. PMID- 2915715 TI - [The immunization status of patients registered with measles during the 1987-88 epidemic]. PMID- 2915716 TI - [Leg lengthening in 2 patients with achondroplasia]. PMID- 2915717 TI - [A fatal complication following pneumonectomy]. PMID- 2915718 TI - [A prescription for clinico-scientific educational research]. PMID- 2915719 TI - [Patient-related research]. PMID- 2915720 TI - [Who survives a serious accident?]. PMID- 2915721 TI - [The use of drugs in the menopause]. PMID- 2915722 TI - [Acute upper respiratory tract obstruction in adults]. PMID- 2915723 TI - [Testing for HIV infection in cardiology]. PMID- 2915724 TI - [Open pulmonary tuberculosis in the 80s]. PMID- 2915725 TI - [Primary pulmonary tuberculosis: more than a 'little flu']. PMID- 2915726 TI - [Breast cancer screening in women younger than 50 years of age: luxury or necessity?]. PMID- 2915727 TI - [Tuberculosis in The Netherlands in 1988]. PMID- 2915728 TI - [Pulmonary and extra-pulmonary forms of tuberculosis; clinical experiences in the 80s]. AB - In the period 1980-1984, 85 patients with tuberculosis were seen at Leyden University Hospital. In this retrospective study clinical data of 76 patients with pulmonary, extrapulmonary, miliary and disseminated tuberculosis are presented. 43 patients suffered from pulmonary tuberculosis. Three patients suffered from miliary tuberculosis and three patients from disseminated tuberculosis. Eight patients suffered from pleuritis tuberculosa, of whom three also suffered from pulmonary tuberculosis. The heterogeneity and often rather non specific, sometimes surprising clinical aspects of tuberculosis are highlighted by a variety of clinical case histories. PMID- 2915729 TI - [The Phadiatop test, a new in-vitro test for inhalation allergy]. AB - The Phadiatop test, a new in-vitro test for inhalant allergy, was evaluated in relation to a RAST panel, and in comparison with total IgE. In 248 patients, aged 12-64 years, who had been prescribed pulmonary medication in general practice, the Phadiatop, total IgE (PRIST), and specific IgE (RAST) test were carried out with seven inhalant allergens common in the Netherlands. RAST was considered positive at class greater than or equal to 2 and total IgE elevated at values greater than or equal to 200, greater than or equal to 150, and greater than or equal to 100 kU/l in age groups 12-14, 15-16, and 17-64 years respectively. The result of the Phadiatop test is given as positive or negative. The predictive value of the Phadiatop test for one or more positive RAST results was 100% and its predictive value for all RAST results being negative was 97.1%, while these predictive values for total IgE were 84.7% and 71.2% respectively. It is concluded that the Phadiatop test is a valuable test to confirm or exclude sensitization to common inhalant allergens. PMID- 2915730 TI - [Visit to the emergency department: primary or secondary character?]. AB - In a prospective study, 961 patients who came to the Emergency Department were registered and their cases were analysed on the basis of criteria drawn up in consultation with a group of general practitioners. Of this number 74% had presented themselves on their own initiative; 40% had been suffering from the complaint for some time. 66% of the patients who had not been referred and 60% of the total number could have been treated by their GP, at less expense for the National Health Service. It is worth considering for GPs on duty to make use of the facilities provided by the Emergency Departments of hospitals. This would increase patients' understanding of the function and the accessibility of Emergency Departments, enable GPs to work more efficiently and be cost effective. PMID- 2915731 TI - [Marginal notes on ketanserin]. PMID- 2915732 TI - [What is the cause of postoperative malaise?]. PMID- 2915733 TI - Factitious diabetes mellitus as part of Munchausen's syndrome. AB - The patient presented here was known to have been suffering from diabetes mellitus for 3 yr, when the suspicion arose that we were dealing with a factitious disease. The coincidence of several other factitious illnesses led us to the diagnosis of Munchausen's syndrome, self-inflicted diabetes mellitus being part of this syndrome. PMID- 2915734 TI - Tubulointerstitial nephritis associated with pyrazinamide. AB - Modern antituberculous therapy consists of a combination of several drugs, some of which (e.g. rifampicin and streptomycin) may cause impairment of renal function. Pyrazinamide therapy has been associated with dose-dependent hepatotoxicity, hyperuricaemia, arthralgia and arthritis. The patient described in this report developed renal failure, fever, arthritis and arthralgia during administration of isoniazid, rifampicin, streptomycin and pyrazinamide. The renal biopsy showed tubulo-interstitial nephritis. After withdrawal of pyrazinamide, while continuing all other drugs, both renal function and histological findings improved which points to an association of renal failure with pyrazinamide. PMID- 2915735 TI - Diagnosis and treatment of thyroid malfunction in The Netherlands. PMID- 2915736 TI - Diagnosis and treatment of Graves' disease. Results of a survey of Dutch internists. AB - The results of a survey of Dutch internists on the diagnostics and treatment of Graves' disease is presented. Eighty-five per cent of all participants chose medical treatment for the uncomplicated patient. Radioiodine was reserved for the case of recurrence after medical treatment and after surgery. Surgical treatment was chosen almost exclusively for a larger goitre by 30% of the participants. Large differences in diagnostics and the treatment were not found between the three categories of hospitals: university, teaching, and general non-teaching hospitals. PMID- 2915737 TI - Treatment of hypothyroidism in The Netherlands. Results of a survey of Dutch internists. AB - The results of a survey on the treatment of hypothyroidism by Dutch internists, working in different types of hospitals, are described. Except in cases of cardiac complications or long-standing disease at old age most patients were treated in the out-patient clinic. About 50% of the internists chose 25 micrograms of levothyroxine as the initial dose for uncomplicated hypothyroidism. A lower dose (12.5 micrograms) was chosen by one-third of the internists working in teaching hospitals and general hospitals, while 36% of the internists working in university hospitals start with 50 micrograms of levothyroxine. For all variants of the basic case of uncomplicated hypothyroidism the dose was even lower. Adjustment of the dose was usually made at fixed intervals combined with measurement of plasma thyroid hormone levels and clinical parameters. The final substitution dose was generally based on the TSH levels. Anticoagulant drugs were seldom used except in cases of cardiac complications. PMID- 2915738 TI - Hypokalaemia in hypertensive patients treated with diuretics: no increase in cardiac arrhythmias. AB - Hypokalaemia is a risk factor for the development of cardiac arrhythmias, at least in patients with a cardiac disease, but it is not known whether this applies to subjects with normal hearts. In the present study, 8 young patients with essential hypertension were treated with chlorthalidone for 12 wk followed by a combination of chlorthalidone (50 mg/day) and triamterene (100 mg/day) for 6 wk. This protocol was chosen in order to create different phases in the intra- and extracellular potassium concentrations. At the end of each 6-wk period, blood analyses were performed together with whole body counting for 40K, 24-h electrocardiogram registration, and ergometry. Although plasma potassium concentration and total body potassium decreased significantly in the chlorthalidone period and increased significantly in the period when triamterene was administered together with chlorthalidone, no changes in ectopic activity were seen during either 24-h registration or ergometry. It is concluded that, although hypokalaemia may be dangerous in patients with diseased hearts, a similar risk could not be established in subjects with a normal heart and uncomplicated essential hypertension. Whether the conclusion applies to the average patient with essential hypertension is still a subject of study. PMID- 2915739 TI - Interpretation of pharmacologic manipulation of urate transport in man. PMID- 2915740 TI - Mesangial glomerulopathy and IgM rheumatoid factor in rheumatoid arthritis. AB - Hematuria and proteinuria in rheumatoid arthritis (RA) are commonly associated with drug therapy but occur independently of drugs, amyloid or urologic disorders. The latter occurrences suggest a primary renal lesion associated with RA. Review of reported renal biopsies identifies mesangial glomerulopathy as a common finding in RA patients without associated drug therapy and that it is frequently associated with hematuria in nonrheumatoid patients. Moreover, immunoglobulins have been shown to concentrate in the mesangium in experimental animals, suggesting that a functional response by the kidney mesangium to remove IgM rheumatoid factor (RF)-IgG complexes could lead to this mesangial lesion. We describe 3 patients with RA who had a mesangiopathy characterized by increased quantities of mesangial matrix and deposition of IgM without other lesions. Together, these observations suggest that: (1) mesangial glomerulopathy is common in RA; (2) removal of circulating RF-IgG complexes is a function of the mesangium and might produce this renal lesion; (3) mesangial glomerulopathy may be responsible for much of the hematuria observed in RA patients and, in many cases, may not be drug related and thus may not require discontinuing beneficial therapy. PMID- 2915741 TI - Persistent wedge-shaped low-density lesions on computed tomography of the kidneys without infarction. AB - A patient with acute lymphoblastic leukemia, who developed acute renal failure, was imaged by computed tomography (CT). Persistent wedge-shaped areas of low attenuation in the kidneys were shown by sequential scans but not areas of infarction were found at autopsy. This case suggests that a wedge-shaped low density lesion on CT may occur not only in infarcted areas, but also in areas where patchy vasoconstriction occurs. PMID- 2915742 TI - Acute metabolic alkalosis during haemodialysis. AB - A 32-year-old woman developed acute metabolic alkalosis during haemodialysis due to dialysate with a very high bicarbonate concentration. This was subsequently discovered to have been caused by the reversed connection of bicarbonate and acid concentrate containers to the entry ports of the Monitral 'S' machine and to failure of the pH meter. Recommendations are made to prevent this potentially fatal accident. PMID- 2915743 TI - Allergic diathesis in patients with IgA nephropathy. PMID- 2915744 TI - Antiglomerular basement membrane glomerulonephritis after inhalation of chemical toxins. PMID- 2915745 TI - Co-dergocrine mesylate (Hydergine) and hypertensive emergencies. PMID- 2915746 TI - Regarding the effect of immune stimulation in idiopathic membranous glomerulonephritis. PMID- 2915748 TI - Pharmacological parathyroidectomy by oral 1,25(OH)2D3 pulse therapy. PMID- 2915747 TI - Cause of persistent hypouricemia in outpatients. AB - We measured serum urate in 3,258 Japanese outpatients. Five of them had persistent hypouricemia. Three also had microhematuria. Four of the five patients were proven to have renal uricosuria with hypouricemia, but otherwise normal tubular function. When tested with both pyrazinamide and benzbromarone, 1 patient had a presecretory reabsorption defect, 2 had postabsorption defects, and 1 an enhanced renal tubular secretion of urate. These results suggest that persistent hypouricemia in outpatients is of very low incidence, is usually caused by an isolated metabolic error of urate transport, and is not related to drug ingestion or systemic disease. PMID- 2915749 TI - Simple technique of inserting modified double-cuffed peritoneal dialysis catheter that allows the placement of inner cuff within the rectus muscle without laparotomy. PMID- 2915750 TI - Massive proteinuria due to renal artery stenosis. PMID- 2915751 TI - Normal glucose tolerance in young patients with nonazotemic chronic glomerulonephritis. PMID- 2915752 TI - The fifth hyperfunctioning parathyroid gland in end-stage renal disease. PMID- 2915753 TI - Does ciclosporin induce clinical remission of dialysis-acquired active chronic hepatitis? PMID- 2915754 TI - Transient hyperoxaluria after ingestion of chocolate as a high risk factor for calcium oxalate calculi. AB - In 6 male subjects the diurnal variation of urinary oxalic acid excretion was studied after ingestion of chocolate, a food stuff rich in oxalic acid. The ingestion of chocolate caused a striking but transient increase in urinary oxalic acid excretion due to its absorption in the upper gastrointestinal tract. The peak excretion rates occurred 2-4 h after the intake of the chocolate. The peak values were 235% of the fasting excretion rate in the trial with 50 g chocolate and 289% in the trial with 100 g chocolate and reached the amounts found in cases with primary hyperoxaluria. The administration of ranitidine had no influence on oxalic acid absorption. The transient hyperoxaluria observed seems to be an important factor for the formation of calcium oxalate calculi in patients on risk for stone disorders. PMID- 2915755 TI - Nocturnal urinary protein excretion rates in patients with sleep apnea. AB - We observed nocturnal urinary protein excretion to be 16.2 +/- 5.5 micrograms/min (mean +/- SE) in 9 healthy control subjects (group I), 29.3 +/- 9.5 micrograms/min in 12 obese patients suspected to have obstructive sleep apnea syndrome (OSAS) but with negative polysomnographic studies (group II), and 94.0 +/- 31.8 micrograms/min in 14 patients with documented OSAS (group III) (II vs. I, NS; III vs. I, p less than 0.05; III vs. II, p less than 0.05). The frequency of abnormal proteinuria, defined as protein excretion greater than the highest rate observed in group I (46 micrograms/min), was 14% in group II and 64% in group III (p less than 0.05). There were no significant differences in age, body weight, body surface area, blood pressure, or indices of sleep apnea between OSAS patients with and without proteinuria. Although the mechanism is unclear, this study shows that nocturnal protein excretion rates are commonly elevated in patients with OSAS. PMID- 2915756 TI - Oxidative metabolism of polymorphonuclear leukocytes and serum opsonic activity in chronic renal failure. AB - Luminol-amplified chemiluminescence was used to study the oxidative metabolism of polymorphonuclear leukocytes (PMN), in resting state and in response to opsonized zymosan, in 65 patients with different degrees of chronic renal failure (CRF) or on regular dialysis treatment (RDT). Every patient was compared on the same day with a normal subject. Furthermore, the serum opsonic activity was evaluated, cross-matching zymosan opsonized by serum from CRF-RDT patients and normals with PMN from CRF-RDT patients and normals. PMN resting chemiluminescence showed a progressive increase inversely related to the glomerular filtration rate, and it remained high in patients on RDT. Zymosan-activated chemiluminescence indicated a deficit in phagocytosis for PMN of patients with a glomerular filtration rate lower than 10 ml/min, persisting in RDT patients. The serum opsonic activity was always significantly lower in CRF and in RDT patients than in the control group; this defect was already present in patients with mild renal impairment. Our findings suggest that PMN from CRF or RDT patients have an increased reactive oxygen metabolite production in the resting state that may cause cell and tissue damage; the opsonization impairment and the decreased PMN phagocytic activity contribute to increased vulnerability to infection in these patients. PMID- 2915757 TI - Catabolic effects of ethanol in chronically uremic rats. AB - Both ethanol consumption and uremia are considered to be associated with wasting, malnutrition and debilitation. The present study was designed to investigate as to whether ethanol exerts a stimulatory effect on the catabolic state of renal failure. Rats underwent 5/6-nephrectomy and were fed either with or without ethanol. The degree of uremia was comparable in both groups. Ethanol-fed uremic rats, however, displayed higher serum levels of urea (+ 103%) and glucose (+29%), as compared to uremic animals without alcohol. Subsequently, the urea N appearance was enhanced (+60%) in uremic rats with alcohol as compared to uremic animals without alcohol. In sham rats urea N appearance was also increased (+39%) following ethanol administration in comparison to sham-operated rats without alcohol, albeit to a lesser degree. Urinary Nt-methylhistidine excretion, an indicator of myofibrillar protein breakdown, was enhanced throughout the experiment in uremic rats receiving ethanol. Finally, ethanol caused higher urinary excretion rates of corticosterone in uremic animals as compared to uremic rats without ethanol. There was a significant correlation between urinary corticosterone excretion and both urea N appearance and urinary Nt methylhistidine excretion. We conclude that ethanol consumption further aggravates the catabolic state of uremia and that this is mediated by an increment in glucocorticoid production. PMID- 2915758 TI - Effect of magnesium diet in gentamicin-induced acute renal failure in rats. AB - Clearance experiments were conducted with metabolic cages to determine the effect of dietary magnesium on gentamicin nephrotoxicity. Three groups of male Wistar rats were given low, medium- or high-magnesium diets. Following baseline clearances, gentamicin was administered by intramuscular injection (20 mg/kg). Additional clearances were performed 6 and 11 days after gentamicin administration. 24-hour clearances were also taken 8 days after gentamicin withdrawal. The present experiments demonstrated that high magnesium intake protected the kidney against injury induced by gentamicin. This reduction in nephrotoxicity was probably due to competition of binding between magnesium and gentamicin to the renal membrane. Histological examinations were also done in these animals. The results showed that the most severe changes were seen in rats receiving a low-magnesium diet. Rats given a high-magnesium diet showed the least toxic changes while rats receiving a medium-magnesium diet showed changes of intermediate severity. These observations complemented the results obtained from 24-hour clearances and indicate the protective effect of dietary magnesium on the development of acute renal failure following administration of gentamicin. PMID- 2915759 TI - Reduction of renal edema by heparin in postischemic renal damage. AB - Rats were subjected to unilateral renal artery clamping for 60 min and contralateral nephrectomy. 125I-labelled fibrinogen and 131I-labelled albumin were injected intravenously 24 h before the experiment. A significant increase in the fibrinogen and albumin content and weight was found already 5 and 15 min after reflow. Rats given heparin (2,000 IU/kg body weight) 5 min before clamping and killed 15 min after reflow showed significantly smaller increases in these values than rats given saline. Morphological studies showed fibrin deposition in Bowman's space, tubules and peritubular capillaries. The results indicate that fibrin deposition occurs and is of importance in the development of renal edema in this type of renal damage. PMID- 2915760 TI - Lipoprotein and apolipoprotein losses during continuous ambulatory peritoneal dialysis. AB - The daily loss of apolipoproteins into the dialysate from 5 patients on continuous ambulatory peritoneal dialysis (CAPD) was measured. The mean excretion of apolipoprotein (apo) AI and apo AII, major proteins of high-density lipoproteins (HDL), were 84 and 17 mg/day, respectively, while that of apo B, a major protein of low-density lipoproteins (LDL) was 39 mg/day. The peritoneal clearance of apo AI and apo AII were similar; both being significantly greater than that of apo B. The fractional catabolic rates of various proteins found in the CAPD dialysate showed molecular sieving effects of the peritoneal membrane and indicated that the apolipoproteins were excreted as lipoproteins. These findings suggest that there is continuous and selective loss of HDL compared to LDL which may also indicate an increased predisposition of these patients to atherosclerosis. PMID- 2915761 TI - Timing of the onset of changes in renal energetics in relation to blood pressure and glomerular filtration in haemorrhagic hypotension in the rat. AB - The timing and circumstances of changes in renal energetics during the gradual induction of haemorrhagic hypotension were studied in anaesthetised rats by phosphorus-31 nuclear magnetic resonance. Animals were bled at a constant rate of 0.1 ml/min via the femoral artery. Whenever changes in renal energetics were seen, a similar pattern was observed. A decrease in adenosine triphosphate occurred rapidly and was always associated with accumulation of inorganic phosphate and tissue acidosis. Profound oliguria, reflecting a markedly decreased rate of glomerular filtration preceded the changes in metabolite levels. Such a fall in glomerular filtration rate and consequently in the energy requirement for tubular reabsorption could be viewed as a mechanism by which energy demands of the kidney are reduced before a critical limitation of energy supply is reached. During uncomplicated haemorrhage in Wistar rats, mean arterial pressures as low as 25-40 mm Hg were reached before changes in renal energetics developed. In contrast, spontaneously hypertensive rates subjected to uncomplicated haemorrhage, and Wistar rats subjected to haemorrhage during concurrent stimulation of the ipsilateral sciatic nerve, developed changes in renal energetics at higher and more variable blood pressures and in response to the withdrawal of lesser but more variable quantities of blood. The sudden onset and severe degree of energy depletion at varying blood pressures during bleeding and its more ready occurrence in animals in which sympathetic nervous activity could be expected to be increased, suggests that sudden renal vasoconstriction is responsible for the unpredictable occurrence of tubular ischaemia in haemorrhagic hypotension. PMID- 2915762 TI - Restrictions on use of creatinine clearance for measurement of renal functional reserve. AB - The increase of glomerular filtration rate after a 90-gram oral protein load was determined in 9 healthy individuals by simultaneous measurements of both creatinine (Ccr) and inulin (Cin) clearances, performed before and every 30 min during 4 h after the meat meal. This protein load resulted in a short 26% increase of Cin at 90 min, and a sustained 29% increase of Ccr from 90 to 240 min after load. Individual peak values of Ccr occurred later than those of Cin (Ccr: 189 +/- 19 vs. Cin: 127 +/- 19 min; p = 0.023). These discrepancies were related to an increase of serum creatinine, and a subsequent increase of the net tubular excretion of creatinine which accounted for up to 15% of the urinary creatinine. The creatinine content of red meat could lead to overestimation of renal functional reserve when measured by creatinine clearance only. PMID- 2915763 TI - L-carnitine addition to dialysis fluid. A therapeutic alternative for hemodialysis patients. AB - L-Carnitine has been reported to have beneficial effects in the reduction of serum triglycerides and increases high-density lipoprotein cholesterol in hemodialysis patients. The published reports are, however, equivocal. Paradoxical increases in serum triglycerides following intravenous administration of L carnitine have been observed. It has been suggested that the paradoxical rise in triglycerides may result from the high doses used and intravenous administration, both of which may cause abnormally high tissue concentrations. In the present study 22 hemodialysis patients were selected. All patients had been treated intravenously with 2 g of L-carnitine administered at the end of dialysis for a minimum of 12 months. Treatment with L-carnitine was then discontinued during a 4 month washout period. The patients were then divided into two equal subgroups and placed on L-carnitine therapy (1 g i.v.) at the end of dialysis for 1 month. Thereafter, L-carnitine was added to the dialysate (2 g in group 1, 4 g in group 2) for 3 months. Serum and muscle carnitine levels were determined throughout the study as were lipid parameters, serum chemistry, and hematology. Muscle biopsies obtained at baseline revealed supranormal levels of carnitine which decreased to normal levels following the 4-month washout period. When therapy with L-carnitine was resumed, intravenous administration or in dialysate, the muscle carnitine levels remained within the normal range. Similarly, serum carnitine was markedly elevated at baseline and decreased to normal during the washout period. When L carnitine was added to the dialysate, total carnitine was observed to significantly increase in the group receiving 4 g.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2915764 TI - Adult T cell leukemia in hemodialysis patients from the Kagoshima district, an area in which human T cell leukemia virus type I is highly endemic. AB - We report 2 cases of adult T cell leukemia (ATL) from hemodialysis (HD) patients with chronic renal failure (CRF) in the Kagoshima district, an endemic area of human T cell leukemia virus type I(HTLV-I) in Japan. The positivity of antibodies to ATL-associated antigen(anti-ATLA) in HD patients, regardless of whether or not blood transfusions were given, has been higher than in healthy persons in the district (p less than 0.01). ATL is considered to break out from HTLV-I carriers. Further study should be conducted to clarify the relationship between HTLV-I infection and CRF, and moreover, attention should be directed not only to treatment of HD but accompanying ATL as well, particularly in HTLV-I-endemic areas. PMID- 2915765 TI - Acute myelogenous leukemia treated with daunomycin associated with nephrotic syndrome. AB - We report a 33-year-old patient with a diagnosis of acute myelogenous leukemia that developed a nephrotic syndrome 9 days after starting treatment with daunomycin. Pathological studies of the kidneys revealed minimal change disease with IgM deposits. Possible pathogenetic mechanisms are discussed. PMID- 2915766 TI - Glycosaminoglycans and urine flow rate. AB - The value of glycosaminoglycans determination in urine has been challenged because the relation between the glycosaminoglycans concentration and other signs of kidney damage is a matter of controversy. It is quite possible that the observed discrepancies could be due to the influence of the urine flow rate, the urine concentration and the time of day on the glycosaminoglycans concentration. Therefore, standardization of the urine sampling time and selection of the most appropriate unit to quantify glycosaminoglycans excretion seem to be essential. PMID- 2915767 TI - Duane's syndrome and focal segmental glomerulosclerosis. PMID- 2915768 TI - Development of traumatic arteriovenous fistula after cannulation of the subclavian vein in a chronic-dialysis patient. PMID- 2915769 TI - Hemodialysis using a Tenckhoff catheter for venous access and a double pump for blood flow. PMID- 2915770 TI - Nifedipine and myoclonic disorders. PMID- 2915771 TI - An easy and effective procedure to prevent radiocontrast agent nephrotoxicity in high-risk patients. PMID- 2915772 TI - Interstitial nephritis induced by cloxacillin. PMID- 2915773 TI - Asynchronous cortical necrosis after bilateral nephrostomy. PMID- 2915774 TI - Early steroid therapy in IgA nephropathy: still an open question. PMID- 2915775 TI - Proteinuria and progression of renal failure in patients on a low-protein diet. PMID- 2915776 TI - Central vein catheters for hemodialysis. PMID- 2915777 TI - [1st Swiss Erythropoietin Symposium. March 25-26, 1988, Beatenberg, Switzerland. Proceedings]. PMID- 2915778 TI - [Assay methods for erythropoietin]. AB - The aim of this contribution is to briefly characterize the assays available for the quantitation of erythropoietin (EPO). The radioimmunological determination of EPO has gained priority for routine and screening measurements. The in vivo bioassay is the most reliable assay for biologic EPO activity. In vitro bioassays should be limited to situations in which radioimmunoassays are not available and for which in vivo bioassays are too insensitive. PMID- 2915779 TI - Treatment of anaemia in haemodialysis patients with recombinant erythropoietin. AB - Recombinant human erythropoietin (r-HuEPO) has been used for the treatment of renal anaemia in haemodialysed patients for more than 2 years. The recommended initial dose is 50 U/kg, intravenously, three times a week, subsequent to the dialysis procedure; if the increase in the haemoglobin level were insufficient after the 4-week therapy, the single doses should be elevated in steps of 25 U/kg each. A weekly total dose of about 200 U/kg (divided into 2 or 3 applications) will normally be adequate to stabilize the haemoglobin value at a level ranging between 10 and 12 g/dl. Patients on r-HuEPO require regular medical supervision, as--along with increasing haematocrit--hypertension and thrombosis of the arteriovenous fistula can develop. A slight increase in serum creatinine and potassium was observed in some of the studies. PMID- 2915780 TI - [Regulation of erythropoietin synthesis]. AB - The main regulatory hormone for the control of erythropoiesis is erythropoietin (EPO). This glycoprotein has a molecular weight of 34,000 daltons, about 40% of which is represented by carbohydrates. EPO leads to an enhanced mitosis and differentiation of erythroid precursors (colony-forming unit erythroid) in the bone marrow by binding to specific receptors. The major stimulus for EPO formation in the kidney is hypoxia. The tubular parts that are intimately involved in this O2-sensing mechanism are the proximal tubular cells as can be inferred from the use of site-specific transport inhibitors. The minimal time necessary for a hypoxic signal to induce EPO formation was found to be 30 min, including wash out of oxygen stores, activation of the EPO gene and equilibration of the EPO distribution space. About 1.5 h after the onset of hypoxia, EPO mRNA was found to accumulate in the kidney, thus pointing toward the possibility of an oxygen-regulated transcription or oxygen-dependent regulation of the stability of EPO mRNA. Possibly, a decrease in the intracellular calcium concentration is involved in this signalling process. PMID- 2915781 TI - [Aerobic and anaerobic capacity of chronic hemodialysis patients under continuous therapy with recombinant human erythropoietin]. AB - In earlier studies we have shown that partial correction of anemia by recombinant human erythropoietin (r-HuEPO) already after 12 weeks results in a significant increase of exercise capacity in patients on chronic hemodialysis. As causative effect increased oxygen availability with improved oxygen delivery to the tissues was assumed. To elucidate the long-term effects of a partial correction of anemia with r-HuEPO on exercise capacity, oxygen uptake at maximum exercise and at the anaerobic threshold was measured by repetitive spiroergometry. Measurements were done before, 3 months and 6 months after initiation of r-HuEPO therapy. The results are summarized below: (table; see text) Our results show that a long-term improvement of peripheral oxygen availability leads to a further increase of anaerobic threshold in patients on chronic hemodialysis even without a further increase of hemoglobin levels and without exercise training. It appears that elimination of the chronic hypoxic condition results in a restoration of previously diminished mitochondrial enzymes in muscle, particularly for aerobic glycolysis. Besides acute improvement of aerobic and anaerobic exercise capacity, the long-term administration of r-HuEPO with its increased anaerobic threshold enhances the patients' everyday life working capacity. PMID- 2915782 TI - [Serum erythropoietin levels in several diseases]. AB - The accurate radioimmunological measurement of serum erythropoietin (EPO) levels has only been possible since the development of highly specific antibodies directed against recombinant human EPO. In the present study, we determined the serum EPO levels in 100 healthy volunteers and in over 300 patients with anemias and hyperglobulinemia of various causes. In the healthy group, the females had levels of 11.3 +/- 3.4 mU/ml, while the males had levels of 8 +/- 3.2 mU/ml. The serum EPO concentrations were inversely related to the degree of anemia in patients with nonrenal anemias, while predialysis patients with renal anemias showed only partially such a tendency. Hemodialysis patients exhibited EPO-levels that were inadequately low relative to the degree of anemia. Patients with hyperglobulinemia had significantly higher serum EPO-levels than healthy individuals and polycythemia vera patients, the latter having particularly low serum EPO levels. Our results show that the determination of serum EPO levels can be of value in the differential diagnosis of hyperglobulinemia. Finally, sequential measurements document fluctuating serum EPO-levels after gastrointestinal hemorrhages and in patients with iron deficiency anemias receiving iron substitution. The probable reason for this phenomenon seems to be the intermittent utilisation of the hormone by EPO-sensitive erythropoietic precursor cells. PMID- 2915783 TI - Correlation of magnetic resonance imaging with neuropsychological testing in multiple sclerosis. AB - Previous research has suggested that cerebral lesions observed on magnetic resonance imaging (MRI) of MS patients are clinically "silent." We examined the validity of this assertion by correlating neuropsychological test performance with MRI findings in 53 MS patients. We used a semiautomated quantitation system to measure three MRI variables: total lesion area (TLA), ventricular-brain ratio (VBR), and size of the corpus callosum (SCC). Stepwise multiple regression analyses indicated that TLA was a robust predictor of cognitive dysfunction, particularly for measures of recent memory, abstract/conceptual reasoning, language, and visuospatial problem solving. SCC predicted test performance on measures on mental processing speed and rapid problem solving, while VBR did not independently predict cognitive test findings. These findings suggest that cerebral lesions in MS produce cognitive dysfunction and that MRI may be a useful predictor of cognitive dysfunction. PMID- 2915784 TI - Diagnosis and management of isolated angiitis of the central nervous system. AB - Isolated angiitis of the central nervous system (IAC) is usually a fatal inflammatory disease with a predilection for small blood vessels. Recurrent cerebral infarction leading to death within a few years is the usual course, but this may be significantly altered by aggressive immunosuppressive therapy with prednisone and cyclophosphamide. Other diseases may, however, present with similar clinical and angiographic features. Because antemortem diagnosis suggests a therapy, establishing the criteria for diagnosis is important. This report describes clinical, angiographic, and biopsy features, and therapy of five successfully treated patients with IAC. The following specific criteria are recommended for establishing an antemortem diagnosis of IAC: (1) clinical pattern of headaches and multifocal neurologic deficits present for at least 6 months, unless the deficits are severe at onset or rapidly progressive; (2) cerebral angiography demonstrating segmental arterial narrowing; (3) exclusion of systemic inflammation or infection; and (4) leptomeningeal/parenchymal biopsy demonstrating vascular inflammation or exclusion of alternate diagnoses. Based upon the successful management of these five previously unreported patients, as well as others in the literature, the following treatment regimens are recommended for the initial 6 weeks of therapy: (1) prednisone 40 to 60 mg/day, and (2) cyclophosphamide 100 mg/day. PMID- 2915785 TI - Neurologic complications of endocarditis: a 12-year experience. AB - We reviewed the neurologic complications in 113 patients with native and 62 patients with prosthetic valve endocarditis. Neurologic complications occurred with the same frequency (35.3% vs 38.7%) and distribution among the two groups. Death occurred in 20.6% of patients with neurologic complications and in 13.6% of patients without neurologic complications (p = 0.23). Staphylococcus aureus endocarditis correlated statistically with the development of neurologic complications (p less than 0.01) and death (p less than 0.01). Among 50 patients discharged from the hospital after receiving only medical treatment for native valve endocarditis, and followed for a mean period of 48 months, there was one patient with mitral valve prolapse and stroke. We conclude that (1) neurologic complications occur with the same frequency in native and prosthetic valve endocarditis, (2) S aureus endocarditis increases the risk of neurologic complications and death, (3) mortality is not significantly increased in patients with neurologic complications, and (4) an episode of treated native valve endocarditis does not increase the natural history of stroke in valvular disease. PMID- 2915786 TI - Common carotid artery occlusion. AB - Symptomatic common carotid artery occlusion (CCAO) is rare. We studied 17 patients with ischemic cerebrovascular symptoms and unilateral CCAO on angiography to help clarify clinical and radiologic features. Mean age was 62 years; 65% were women. Predominant symptoms and signs included visual-ipsilateral monocular or retrochiasmal symptoms (88%), motor weakness (88%), sensory disturbance (59%), dizziness/lightheadedness (53%), and syncope (24%). Dysarthria, headache, or involuntary limb shaking occurred less frequently. Positionally related symptoms occurred in approximately two-thirds of the patients. TIAs were often multiple and preceded a stroke or occurred without subsequent stroke in 82%. Hemispheric TIAs contralateral to the CCAO occurred in 41%. Ten patients (59%) suffered stroke, seven (70%) of which were ipsilateral to the CCAO. Vascular risk factors included cigarette use (76%), hypertension (71%), diabetes mellitus (41%), and hyperlipidemia (41%); 82% had two or more risk factors. Known cardiac disease was present in 59%. CCAO was present at the origin of the vessel in most patients. Most had atherosclerotic narrowing of multiple extracranial large vessels. During follow-up, none of the patients had a spontaneous second infarct; five had TIAs, including two with amaurosis fugax, all in the CCAO territory. More restricted external carotid collaterals may, in part, explain the higher frequency of ipsilateral stroke and contralateral TIAs than reported for internal carotid occlusion. PMID- 2915787 TI - Intraoperative brainstem auditory evoked potentials: significant decrease in postoperative morbidity. AB - Evoked potentials are commonly used for intraoperative monitoring of neural tissue under surgical threat despite the lack of unequivocal evidence demonstrating its effectiveness in preventing neural injury. This study retrospectively compares the auditory morbidity of posterior fossa microvascular decompressive surgery before and after the introduction of intraoperative brainstem auditory evoked potentials (BAEPs). All patients underwent a similar operative procedure performed by a single surgeon. The two groups were comparable with regards to age, sex, and indications for surgery. In the nonmonitored group, auditory morbidity had not declined with increasing experience of the surgeon. Ten of 152 patients (6.6%) suffered a profound hearing loss in the nonmonitored group. In the monitored group, none of 70 patients suffered a profound hearing loss. We attribute this significant decline (p = 0.02) in morbidity to the introduction of intraoperative BAEPs. We believe this to be the first demonstration of a significant decrease in operative morbidity directly associated with the use of intraoperative evoked potential monitoring. PMID- 2915788 TI - The "yips": a focal dystonia of golfers. AB - The "yips" is an involuntary motor disturbance affecting golfers. A 69-item questionnaire was constructed and distributed to 1,050 professional and amateur golfers in an effort to define and characterize this syndrome. Of the male golfers there was a 42% response rate and 28% reported suffering from the yips. The disorder was described most frequently as jerks, tremors, and spasms affecting the preferred arm distally and primarily during putting. When compared with unaffected golfers, afflicted golfers were significantly older and had more cumulative years of golfing. In 24%, activities other than golfing were affected and 25% reported involvement of body regions beyond the arms. These data support the hypothesis that the yips represents a focal dystonia and shares many features with other occupational dystonias. PMID- 2915789 TI - Dystonic posturing in complex partial seizures of temporal lobe onset: a new lateralizing sign. AB - We observed unilateral dystonic posturing of an arm or leg in 41 complex partial seizures (CPS) from 18 patients. In all cases this was contralateral to the ictal discharge. Unilateral automatisms occurred in 39 of 41 seizures on the side opposite the dystonic limb. Version occurred in 11 of the 41 CPS to the same side as the dystonic posturing and always followed the posturing. Subdural recordings of seven seizures showed ictal onset from the mesial basal temporal lobe. At the onset of dystonic posturing, maximum ictal activity was in the basal temporal lobe with minimal involvement of the cerebral convexity. Unilateral dystonic posturing occurs frequently in CPS of temporal lobe onset and is a lateralizing sign with a high degree of specificity. It probably reflects spread of the ictal discharge to basal ganglia structures. PMID- 2915790 TI - The effects of storage and shaking on the settling properties of phenytoin suspension. AB - Phenytoin suspension (PHY-S) is reported to settle, resulting in uneven drug distribution and variable patient dosing. We designed this study to determine the rate of settling and the amount of agitation needed to resuspend the preparation. To determine the rate of settling, we thoroughly shook three bottles of PHY-S and then left them undisturbed. We took samples from the top and bottom of each bottle with a microsyringe at 15 minutes, 1, 6, 12, 24, 48, and 72 hours, and 1, 2, 3, 4, and 5 weeks. We simulated patient administration with daily doses that were measured under good, fair, and poor shaking techniques. We analyzed samples after every tenth dose. After complete resuspension the active ingredient in PHY S settles at a very slow rate. We found no differences in concentration between the top and bottom until the fifth week in the bottles thoroughly shaken and left undisturbed. Minimal agitation is required to resuspend PHY-S. The well-shaken and poorly shaken bottles in the patient simulation phase exhibited no differences in concentrations whereas the unshaken bottle had differences throughout the study period. Problems thought to be associated with PHY-S may be related to compliance and inaccurate measuring devices. PMID- 2915791 TI - Persistent cognitive impairment in climbers after repeated exposure to extreme altitude. AB - We performed neuropsychological testing in eight world class climbers who had reached summits higher than 8,500 meters without supplementary oxygen. Five had mildly impaired concentration, short-term memory, and ability to shift concepts and control errors. There were no defects in perception or other cognitive activities. The pattern of impairment suggests malfunctioning of bifronto-temporo limbic structures. Repeated extreme-altitude exposure can cause mild but persistent cognitive impairment. PMID- 2915792 TI - Transient global amnesia: evidence for extensive, temporally graded retrograde amnesia. AB - We gave six patients with transient global amnesia (TGA) neuropsychological tests during and after their episodes. During TGA, all patients had severe anterograde amnesia for verbal and nonverbal material and a patchy but temporally graded retrograde amnesia for personal and public events dating back to at least 1960. In addition, they were unusually passive during TGA, had impaired ability to copy a complex figure, and possibly had mild impairment of confrontation naming. All exhibited complete recovery of memory and other cognitive abilities after the episode. There are similarities between the transient amnesia of patients with TGA and the chronic amnesia of patients with presumed bilateral damage to the medial temporal region or the diencephalic midline. PMID- 2915793 TI - Neurologic findings in men with isolated hypogonadotropic hypogonadism. AB - We studied the neurologic abnormalities in 41 men with isolated hypogonadotropic hypogonadism. Findings included anosmia, hyposmia, mirror movements, ocular motor abnormalities, cerebellar dysfunction, and pes cavus foot deformity. One-third of the subjects had a family history of delayed sexual maturation. Patients with a family history of delayed sexual maturation had a significantly higher incidence of olfactory dysfunction, mirror movements, and pes cavus foot deformity. Our data suggest that isolated hypogonadotropic hypogonadism and its accompanying neurologic abnormalities may arise from a genetically linked developmental abnormality of CNS structures. PMID- 2915794 TI - Spinal cord pathology in pediatric acquired immunodeficiency syndrome. AB - We examined the spinal cords from 15 consecutive autopsies of infants and children with AIDS using a battery of histochemical and immunocytochemical stains, and in four cases, electron microscopy. Corticospinal tract (CST) signs were a notable clinical finding in 14; however, the age of onset, rate of progression, severity of dysfunction, and duration varied among patients. Ten cases had pathologic changes in the CST. In four of the ten cases, the changes were consistent with an "axonopathy" since axons and myelin were both diminished in the CST. These cases may represent CST wallerian degeneration, since they had marked injury to cerebral white matter in the form of chronic inflammation with multinucleated cells, gliosis, and myelin pallor. In five cases, with an average age at death of 31 months, the CST showed poor myelination with relative preservation of axons. These cases may represent delayed myelination or possibly cytokine-mediated injury to newly formed myelin since the CST is one of the last tracts to myelinate in the spinal cord. One child with primary CNS lymphoma had a complicated pattern of spinal injury due to unilateral CST wallerian degeneration possibly superimposed upon delayed myelination, in addition to patchy areas of demyelination associated with perivascular lymphomatous infiltrates. Four children with mild CST signs, ranging in age from 5 to 6 months, had CST myelin pallor that was consistent with the degree of myelination expected for age. We did not find vacuolar myelopathy similar to that seen in adult AIDS, but did note focal vacuolar changes in the thoracic posterior columns in the oldest child. PMID- 2915795 TI - Autopsy findings in a patient who had an adrenal-to-brain transplant for Parkinson's disease. AB - Autopsy findings in a patient who had an adrenal-to-brain transplant for Parkinson's disease 4 months before his death showed adrenal tissue in the basal ganglia, but it was necrotic. Symptomatic improvement lasted for only 2 weeks. PMID- 2915796 TI - Cerebrocortical microdysgenesis in neurologically normal subjects: a histopathologic study. AB - Previous studies showed that few foci of cerebro-cortical microdysgenesis (molecular layer neuronal ectopias and focal laminar dysplasia) are present in up to 26% of variably processed normal brains; they are more common in the right inferior frontal region. Brains of male developmental dyslexics processed in serial histologic sections showed 30 to 140 foci of these types of anomalies, predominantly in left perisylvian cortex. Here, we present the results of a detailed analysis of ten normal brains also processed in serial sections. The ages ranged from 3.5 to 87 years, all male. Three brains showed abnormalities similar in type to those of the dyslexic, but in far smaller numbers and in different locations: two showed a single cingulate focus--one right, one left; the third brain showed two right supratemporal foci. We conclude that the present form of developmental anomaly is rare in normal brains, and that the findings in the dyslexic brains may be significant. PMID- 2915797 TI - Hereditary sensory neuropathy with deafness: a familial multisystem atrophy. AB - We report a 39-year-old woman with hereditary sensory neuropathy-type I (HSN-I) and deafness--Hicks' disease. The cochlea showed cell loss in the organ of Corti, and spiral ganglia and atrophy of acoustic nerves. Morphometric and quantitative studies of the ventral cochlear nucleus disclosed mild changes resulting from transynaptic atrophy. There was, however, neuronal as well as severe dendritic loss and gliosis in the auditory and sensory cortex that could not have been caused by their functional deprivation or have resulted from a chain reaction of transynaptic atrophy, since their corresponding lower relay nuclei did not display significant atrophy. The finding of cell loss and gliosis in the thalamus in nuclei that do not subserve these two pathways as well as in the red nuclei, inferiro olivary nuclei, and claustrum suggested that HSN-I with deafness is nosologically related to familial multisystem atrophy. PMID- 2915798 TI - Sulfite oxidase deficiency: clinical, neuroradiologic, and biochemical features in two new patients. AB - Sulfite oxidase deficiency is characterized by severe neurologic dysfunction, dislocation of the lenses, and the accumulation and excretion of inorganic sulfite, thiosulfate, and S-sulfocysteine. We present the clinical, radiologic, and biochemical findings in two patients with this condition. In both, neurologic problems started soon after birth and progressed rapidly to profound mental retardation, microcephaly, blindness, and spastic quadriparesis. Seizures were a persistent problem throughout the course of their illness. The neurologic abnormalities were associated with progressive destruction of brain tissue. We established the diagnosis of sulfite oxidase deficiency by demonstrating the characteristic abnormal metabolites in urine. However, commonly used screening procedures do not detect these compounds, and dislocation of the lenses is usually a late feature of the disease. As a result, the diagnosis may be easily overlooked, especially during infancy. Specific investigations for sulfite oxidase deficiency are indicated for any baby with severe, progressive neurologic disease. PMID- 2915799 TI - Prevalence of multiple sclerosis in Lanzarote (Canary Islands) AB - In the island of Lanzarote of the Province of Las Palmas, which is part of the Spanish archipelago of the Canary Islands, the prevalence of multiple sclerosis is 15 per 100,000. The prevalence of MS in Lanzarote seems related more to ethnic conditions than to geography. PMID- 2915800 TI - Reliability of the diagnosis of a first seizure. AB - We studied the interrater variability among three neurologists of the diagnosis of a seizure in 100 patients evaluated for a possible "first seizure." We found that use of simple descriptive diagnostic criteria and discussion among the neurologists themselves improved the diagnostic agreement. PMID- 2915801 TI - Absence of humorally mediated damage within the central nervous system of AIDS patients. AB - The pathogenesis of CNS damage by human immunodeficiency virus infection is unclear. Because there is little detectable virus within the CNS, we evaluated the role of the humoral immune system in mediating CNS tissue destruction. The paucity and nonspecific nature of immunoglobulin deposition rules against significant involvement of humorally mediated injury in the pathogenesis of AIDS encephalopathy. PMID- 2915802 TI - Heterogeneity evidence and linkage studies on Charcot-Marie-Tooth disease. AB - Charcot-Marie-Tooth neuropathy type 1 (CMT1) is an autosomal dominant disorder originally localized to chromosome 1 by linkage to the Duffy blood group. Studies have since shown that the disorder may be heterogeneous, as not all families show this linkage. We tested genetic heterogeneity by the HOMOG computer program in 15 CMT1 pedigrees informative for Duffy. We detected no evidence for heterogeneity in this sample, but when we combined results with previously published lod scores, heterogeneity was statistically significant. Twelve of the 15 families studied did not show linkage to Duffy. We found six of these families to be informative for a chromosome 19 marker, apolipoprotein CII (ApoC2). Despite a previous report showing probable linkage of a non-Duffy-linked CMT1 pedigree to two chromosome 19 markers, we did not detect significant linkage of ApoC2 to CMT1 in these families. PMID- 2915803 TI - A case of Alzheimer's disease and hippocampal sclerosis with normal cholinergic activity in basal forebrain, neocortex, and hippocampus. AB - A 76-year-old man without apparent dementia met pathologic criteria at autopsy for Alzheimer's disease, which included a maximum senile plaque density greater than 15 per square millimeter of neocortex. Despite hippocampal sclerosis, changes typical of Alzheimer's disease were not found in this region or in basal forebrain. Choline acetyltransferase activity in hippocampus, septum, and parietal cortex was normal. PMID- 2915804 TI - Caudal thalamic infarction following intranasal methamphetamine use. PMID- 2915805 TI - Meningitis following spinal puncture in a patient with a CSF leak. PMID- 2915806 TI - Etiology of syringomyelia. PMID- 2915807 TI - MS in Saudi Arabia. PMID- 2915808 TI - Cerebral metabolism in Alzheimer's disease. PMID- 2915809 TI - Primary intraventricular hemorrhage. PMID- 2915810 TI - American Academy of Neurology. 41st annual meeting. Chicago, April 13-19, 1989. Abstract listing & general meeting information. PMID- 2915811 TI - [Teaching-learning. The reform of the study plan and new didactic modalities]. PMID- 2915812 TI - [The prognosis of multiple sclerosis: a contribution]. AB - A number of clinical characteristics of multiple sclerosis that may influence prognosis quo ad valetudinem are considered; onset with optic neuritis and frequency of recurrence less than 0.5/annum in the first three years of disease seem to be associated with a slower degree of deterioration (measured by the progression index). The age of onset, sex and type of disease would not appear to influence the prognosis. PMID- 2915813 TI - [The role of radiotherapy in the treatment of supraglottic laryngeal tumors. Case reports]. AB - Radiotherapy obtains better results when employed alone, in initial forms (T1 T2), and after surgery, when loco-regional relapse incidence reduces. Personal results in the treatment of laryngeal cancer are reported in 281 patients. One hundred-forty-seven patients treated with exclusive radiotherapy had 5-year global and NED survival of 32.7% and 26.6%; 5-year NED survival in particular was 78.7% for T1-T2 and 22.9% for T3-T4. Subsequently 52.8% of patients relapsed. One hundred-thirty-four patients treated with postoperative radiotherapy had a 5-year global and NED survival of 58.8% and 52.1%; relapses were observed in 20.9% of patients, mostly in cases with histological G3 grading or with rupture of the lymph node capsule. The importance of exclusive and postoperative radiotherapy with reference to prognostic factors that are deduced from the histological specimen is underlined. PMID- 2915814 TI - [AIDS: the acquired immunodeficiency syndrome]. AB - AIDS (acquired immune deficiency syndrome) is a disease of major medical, epidemiological, psychological and social importance. Its aetiological agent is one of the retroviruses that attacks the individual's immune system and destroys its ability to combat other diseases. The available virological data make it clear that the disease mainly attacks risk categories such as homosexuals, drug addicts, people receiving repeated blood transfusions, haemophiliacs as well as the sexual partners and children of these groups. Blood tests for AIDS diagnosis via the identification of the anti-HTLV-III antibody were performed and the ELISA method was used to test samples from the following groups: blood donors, outpatients and drug addicts. A high incidence of positivity was found among the drug addicts. PMID- 2915815 TI - [Treatment of amyloidosis with dimethyl sulfoxide (DMSO)]. AB - In this study we have investigated the role of oral dimethylsulfoxide (DMSO) therapy in 2 patients with primary amyloidosis (AL) and in 2 patients with secondary amyloidosis (AA) to long-standing rheumatoid arthritis. DMSO treatment produced no beneficial effects in the patients with idiopathic amyloidosis. Instead the patients with secondary amyloidosis experienced a subjective improvement, a decrease of inflammatory activity of the rheumatoid arthritis and an unequivocal improvement of renal function following 3-6 months of DMSO therapy. No serious side effects of DMSO were observed except for unpleasant breath odour. We conclude that a treatment with oral DMSO may prolong life of patients with secondary amyloidosis. PMID- 2915816 TI - [Spontaneous platelet aggregation after experimental focal ischemia in the rabbit. "Sensitivity", "specificity" and value of the test used]. AB - Within the framework of an investigation at present under way at the Neurological Clinic of Pavia on experimental focal ischaemia, the peculiarities of platelet aggregation observed, have led to a more accurate assessment of both the phenomenon itself and the validity of the method used. In a group of 30 rabbits (17 of them submitted to embolization by means of microspheres introduced into the carotid and 13 used as controls), biohumoral electrical and histological parameters were examined. The spontaneous platelet aggregation test proved significantly related to the extent of changes taking place, as measured by PDS levels and QEEG "delta" activity (respectively, P less than 0.005 and P less than 0.05). Platelet aggregation, in relation to the occurrence or absence of focal ischaemia, revealed a "sensitivity" of 80% and a "specificity" of 92.3%. When not only the onset of but also the increase in aggregation is taken into account, the "sensitivity" figure appears to go up to 93.3%. Endothelial damage and "cascade" platelet aggregation appeared to be a prerequisite for the occurrence of the changes found. In these changes, the pathogenetic role of the regional vasospasm as opposed to mere mechanical obstruction seems to be confirmed. On the basis of these findings, it is concluded that the identification of spontaneous platelet aggregation using K. Breddin's method and its quantification based on Born's turbidimetric principle, may be usefully employed to assess the risk factor constituted by an abnormal tendency to platelet hyperaggregation. PMID- 2915817 TI - [Multiple myeloma and retroperitoneal fibrosis]. PMID- 2915818 TI - Ethics or enigmas? PMID- 2915819 TI - Biomedical ethics. A time of change. PMID- 2915820 TI - MSNJ and biomedical ethics. PMID- 2915821 TI - The courts and the PVS patient. PMID- 2915822 TI - Covenant-making and medical ethics. PMID- 2915823 TI - Biomedical ethics. A quest for balance. PMID- 2915824 TI - Committee on Biomedical Ethics. PMID- 2915825 TI - Medical education's ethical challenge. PMID- 2915826 TI - The challenge of ethics. PMID- 2915827 TI - Nursing homes and ethics committees. PMID- 2915828 TI - Ethics in high school. PMID- 2915829 TI - Biomedical ethics. The democratic imperative. PMID- 2915830 TI - UMDNJ notes. PMID- 2915831 TI - AMNJ report (Academy of Medicine of New Jersey). PMID- 2915832 TI - Deaf persons and a hearing therapist. PMID- 2915833 TI - [The risk of falling in the hospital]. PMID- 2915834 TI - [Subcutaneous epidural catheter for the treatment of pain]. PMID- 2915835 TI - [Bladder rehabilitation in the quadriplegic male]. PMID- 2915836 TI - [Amputation black on white]. PMID- 2915837 TI - Health tomorrow depends on our role in society today. PMID- 2915838 TI - [Evelyn Rocque Malowany: an entrepreneur. Interview by Nicole Rodrigue]. PMID- 2915839 TI - [Women in trouble: greying of the sun]. PMID- 2915840 TI - [For better understanding of urinary incontinence]. PMID- 2915841 TI - [The World Health Organization--do you know about it?]. PMID- 2915842 TI - [Community health visits: appreciation and impact]. PMID- 2915843 TI - The new era begins. PMID- 2915844 TI - Changes in education--undergraduate education and training in dentistry in New Zealand. PMID- 2915845 TI - The radiographic assessment of pulp size: validity and clinical implications. AB - A study was performed to determine if the radiographic appearances of the coronal pulp spaces provide a reliable indication of pulp size in maxillary incisors. The use of student and staff assessor groups showed that length of clinical experience did not influence assessments of the size of the coronal pulp. A measuring grid, superimposed over a duplicate set of films, decreased the students' perception of the size of the coronal pulp. The presence of small carious lesions or restorations did not affect the assessments for either of the film types viewed. The data were pooled to give a mean radiographic size for each tooth, and the teeth were sectioned. Analysis of the results demonstrated the value of carefully viewing incisor crowns shown on pre-operative periapical radiographs. Sectioning of the teeth suggested that very little dentine may remain to protect the pulp after routine crown preparations. Even the very conservative preparations sometimes necessary when providing veneers might be considered a hazard to the pulp, as they may expose large areas of the dentine of an immature tooth. PMID- 2915846 TI - Facial abscess: a case report. AB - This report describes a patient with a migratory abscess as a sequel to the surgical removal of a mandibular third molar tooth. Culture of pus drained from the abscess revealed no growth, probably because of previous management with antibiotics. PMID- 2915847 TI - Practitioners and teaching. PMID- 2915848 TI - Child abuse in the dental operatory. PMID- 2915849 TI - Patients' knowledge of caries prevention. A study. AB - This study explored the caries prevention awareness of a population of regular dental patients. Although regular dental patients have an overall high knowledge about certain aspects of caries population, they do not have accurate information about fluoride, tooth-brushing and minimal knowledge about sealants. Establishing the patients' knowledge of the prevention of tooth decay is important in determining strategies and implementation of public health education programs and education programs in individual dental offices. PMID- 2915850 TI - Suit to declare AIDS communicable disease. PMID- 2915851 TI - Dentistry for children. The changing picture. PMID- 2915853 TI - Type C lesions. PMID- 2915852 TI - Pyrrhic victory? PMID- 2915854 TI - Sedation and general anesthesia. PMID- 2915855 TI - Cesarean scar endometriosis: a review. AB - Endometriosis in the abdominal scar following cesarean section is a rare event, but may be more frequent than estimated from the literature. Five cases collected over 5 years are presented suggesting an incidence over 1 percent. Diagnosis and management are discussed and the literature regarding this entity is reviewed. Newer methods of treatment are available, but surgical excision remains the method of choice. PMID- 2915856 TI - Management of human papillomavirus-associated genital lesions in men. AB - A total of 155 men with human papillomavirus (HPV)-associated genital lesions were studied to evaluate therapy for obvious and subclinical lesions. The treatment methods were selected according to type, location, size, and number of lesions. Seventy-three percent of all patients were successfully treated by the initial therapy. Eighty men with minimal disease had a significantly lower treatment failure rate than 75 men with multiple lesions (15 versus 40%; P less than .001). The type of lesions (classical condyloma versus other HPV-associated lesions), visibility (obvious condylomata versus subclinical lesions), and location did not significantly influence the cure rate (P greater than .05). Seventy-six percent of treatment failures were evident at the first follow-up examination. After a follow-up time of 1 year, 95% of men with obvious condylomata and 93% of men with subclinical lesions were disease-free. The results indicate that obvious and subclinical HPV-associated lesions in men may be successfully controlled by one or more treatment modalities adapted to the particular needs of the patient. PMID- 2915857 TI - Genital Chlamydia trachomatis infections in patients with abnormal cervical smears: effect of tetracycline treatment on cell changes. AB - A group of 1760 women aged 14-35 years were examined for the concurrent presence of Chlamydia trachomatis and cellular atypia of cervical smears. Positive tests for C trachomatis were found in 126 women (7.2%). Cell changes were found in 85 women (4.8%), and 25 of these were C trachomatis-positive. Slight cellular atypia was the major finding in the smears from 22 of the C trachomatis-positive women, whereas three patients had more pronounced cell changes. Smears reverted to normal in 18 of the 23 patients who returned for tetracycline treatment and follow-up cytology. All 18 patients had smears showing slight cellular atypia prior to therapy. In five patients who also had cellular changes suggesting a human papillomavirus infection, the smears did not revert to normal after antibiotic therapy during the observation period. These findings suggest that patients with C trachomatis and mild cellular atypia should have antibiotic therapy and repeat smears taken before further treatment is considered. More advanced cellular atypia is unlikely to be caused by C trachomatis. PMID- 2915858 TI - Peritoneal fluid cytology and prognosis in patients with endometrial carcinoma. AB - Cytologic examination was performed on peritoneal fluid collected from a total of 235 consecutive patients with endometrial carcinoma who underwent laparotomy as the initial treatment at the Cancer Institute Hospital from 1971-1985. The rate of cases positive for cancer cells in the peritoneal cytologic examination was 18.7% for all stages (44 of 235 cases). In stage I endometrial carcinoma, the 5 year and 10-year cumulative survival rates with positive peritoneal cytologic findings were 91.6 and 90.0%, respectively; those in cases with negative cytologic findings were 90.2 and 90.2%, respectively, with no significant difference. The recurrence rate in the same stage was 12.0% for cytologically positive cases versus 9.5% for negative cases. In stages II and III, no significant difference was noted in the survival rate between nine cases with positive peritoneal cytologic findings without macroscopic peritoneal metastasis and 47 comparable cases with negative cytologic findings. Therefore, in endometrial carcinoma, the presence of malignant cells in peritoneal fluid is not a useful prognostic factor. PMID- 2915859 TI - CA 125 in peritoneal washings and fluid: correlation with plasma CA 125 and peritoneal cytology. AB - Sixty-four women with ovarian cancer and 46 controls with benign gynecologic conditions underwent cytologic and CA 125 evaluations of peritoneal fluid or peritoneal washings at laparotomy. These parameters were correlated with preoperative disease status, intraoperative findings, and preoperative plasma CA 125 levels to determine their value in assessing occult disease. No false positive cytology reports were observed. Cytology specimens were positive in 20 of 23 patients (87%) with clinical evidence of disease who had peritoneal fluid present, but in only 18 of 29 (62%) of similar patients with no peritoneal fluid present (P less than .05). CA 125 values were elevated in 16 of 23 (69.5%) and 15 of 29 (52%) of these samples, respectively (P greater than .05). Levels of CA 125 in peritoneal fluid washings correlated poorly with the presence of obvious intraperitoneal cancer and had questionable reliability when used to evaluate patients clinically free of disease. Positive peritoneal cytology reflected the presence of ovarian cancer, but its absence did not mean that an objective response to chemotherapy treatment had occurred. Disease status correlated best with physical examination and circulating levels of CA 125. PMID- 2915860 TI - VM-26-vincristine-cisplatin combination chemotherapy in the treatment of primary advanced and recurrent endometrial carcinoma. AB - A chemotherapeutic combination consisting of VM-26-vincristine-cisplatin was used to treat 44 consecutive patients with primary advanced or recurrent endometrial carcinomas. Nine complete remissions (20.5%) and 14 partial remissions (31.8%) were recorded. The median duration of remission in responders was 8 months (range 1-35). The responding patients had significantly longer survival than nonresponders. The median duration of survival in the complete series was 7 months. The response rates and survival times were the same for primary advanced tumors and recurrences, regardless of sites. Peripheral neuropathy, secondary anemia, and nausea were the most common side effects. The drug combination was well tolerated, and its efficacy is comparable to that of other more toxic chemotherapy regimens. PMID- 2915861 TI - Long-term tocolysis with intravenous magnesium sulfate. AB - Although the tocolytic effect of magnesium sulfate is well known, it has generally been used for this purpose for only brief periods. In this study, we administered intravenous magnesium sulfate tocolysis, either alone or in combination with other tocolytics, to 111 women as follows: 1) 60 (54%) received the drug for 3 or fewer days (short-term group); 2) 29 (26%) received the drug for 3-10 days (intermediate group); and 3) 22 (20%) received the drug for 10 days or longer (long-term group). Side effects (ileus and/or constipation, visual blurring, headache) were more common in the intermediate and long-term groups, but no life-threatening complications were seen. The drug was discontinued because of side effects in 7% of the patients in each group. We believe our data indicate that there need be no time limit and that magnesium sulfate tocolysis may be continued as clinically indicated. PMID- 2915862 TI - The prevalence and distribution of acute placental inflammation in uncomplicated term pregnancies. AB - The clinical relevance of histologic evidence of acute ascending intrauterine infection has been called into question by descriptions of "silent" chorioamnionitis. The described frequencies of silent chorioamnionitis in normal and abnormal pregnancies vary widely because of differences in the definition of a normal pregnancy, methods of placental examination, and pathologic criteria. Therefore, we examined placentas from 161 uncomplicated gestations for the presence and severity of acute inflammation in the amnion, chorion-decidua, chorionic plate, and umbilical cord using strict gross and microscopic protocols. Indicators of amniotic fluid infection, specifically umbilical cord inflammation, amnionitis, and inflammation within the chorionic plate were present in 0, 1.2, and 4% of the cases, respectively. Silent chorioamnionitis was rare. There was a statistical association between the presence of acute inflammation and the occurrence of labor at term. Methods of tissue sampling that included a more extensive examination of the site of membrane rupture resulted in an increased frequency of diagnosis of acute inflammation at the site of rupture in vaginal deliveries at term. PMID- 2915863 TI - Information management needs of the obstetrician-gynecologist--a survey. AB - A random sample survey of members of The American College of Obstetricians and Gynecologists (ACOG) was conducted to ascertain the extent to which computer technology was being used by the members, and what further computer services and applications were needed. Computers were used by 38% of the members, with an additional 13% planning on getting a computer within the year. An average of 48% of the members had no plans for computerization, although this number was lower (29%) for physicians 36-45 years of age. There was no significant variation of use by physician sex or type of practice (office- versus non-office-based). Word processing and financial management were the most frequently used computer applications; clinical patient care tasks were used much less frequently and were presumably less available, because software for these tasks was also highly desirable. The most desired information services were uniform coding and terminology, high-risk patient management, electronic access to full-text obstetric and gynecologic data bases, and online clinical management protocols. Prescription writing, patient recall by drug, and drug inventory computer applications were among the least requested. Several educational, project development, communication, and member service strategies have been formulated to integrate medical information management activities for ACOG members. PMID- 2915864 TI - Endometrial sampling prior to hysterectomy. AB - Many gynecologists use routine endometrial sampling prior to hysterectomy to detect an unsuspected endometrial carcinoma. Gynecologists who formerly performed uterine curettage under anesthesia before hysterectomy now often use an outpatient endometrial sampling technique. Although safe, this procedure is complicated by discomfort, cost, and the risk of infection or uterine perforation. The purpose of this study was to determine the utility of pre hysterectomy endometrial sampling. Between 1981-1985, 619 patients undergoing hysterectomy had preoperative endometrial sampling using Vabra aspiration, the Novak curette, or D&C. The endometrial sampling histology was compared with that in the hysterectomy specimen. There were 30 instances in which the endometrial sampling failed to identify either endometrial hyperplasia or carcinoma. In the two cases of endometrial carcinoma, D&C was the sampling method used. The findings of this study indicate that these three techniques of endometrial sampling are equal in their diagnostic capabilities. The results confirm the need for biopsy in patients with postmenopausal bleeding or with abnormal uterine bleeding at age 35 years or older. Our findings do not support routine endometrial sampling prior to hysterectomy. PMID- 2915865 TI - Vulvar vestibulitis--subgroup with Bartholin gland duct inflammation. AB - Some women with vulvar vestibulitis have tenderness at the Bartholin gland duct opening and associated dyspareunia. Forty-four patients with severe incapacitating dyspareunia of up to 5 years' duration were studied. Microscopic examination revealed a chronic inflammation located near the Bartholin gland duct opening. No etiologic agent was evident. Of 30 women treated initially with laser vaporization of inflamed areas, 13 (43%) showed significant improvement. Sixteen patients were treated with perineoplasty and all improved significantly; all became functional sexually although eight had previously failed laser therapy. Women with vulvar vestibulitis can be identified easily with a simple Q-tip touch technique directed at the duct opening. This diagnosis should be considered in the evaluation of women with obscure etiologies of dyspareunia. PMID- 2915866 TI - Brief sexual inquiry in gynecologic practice. AB - Eight hundred eight-seven consecutive gynecologic outpatients were screened for sexual concerns and dysfunctions by the inclusion in the medical history of two questions concerning sexual function. Only 29 women (3%) spontaneously offered sexual complaints without direct inquiry. An additional 142 women (16%) acknowledged sexual problems upon questioning. The most common sexual complaint was dyspareunia (48%), followed by decreased sexual desire (21%), partner problem(s) or dysfunction(s) (8%), vaginismus (6%), anorgasmia (4%), and other problems (13%), eg, arousal problems, decreased lubrication, sexual anxiety, etc. Sexual complaints were more prevalent in those 50 years of age or older. This brief sexual inquiry added little time to the office visit, and most of the sexual complaints could be resolved by the gynecologist. PMID- 2915867 TI - Intrapartum uterine activity: evaluation of an intrauterine pressure transducer. AB - A newly available intrauterine pressure transducer was evaluated clinically in 100 patients. Successful insertion was accomplished in 95%. There were no significant intrapartum maternal or fetal complications. Partial dehiscence of a surgically scarred uterus did occur in one patient who received the device, but a clear relationship between its attempted insertion and the dehiscence was not apparent. Early in the clinical trial, a number of devices malfunctioned; the manufacturer defined and remedied the problem. The intrauterine transducer required no maintenance and appeared to be practical in laboring women. We suggest that the utility of the intrauterine pressure transducer might be enhanced with several modifications, including the addition of a re-zeroing mechanism and a reduction in the device's length. PMID- 2915868 TI - Use of the fibrin D-dimer in screening for coagulation abnormalities in preeclampsia. AB - Plasma from pregnant women with preeclampsia was screened for the D-dimer, a degradation product specific for crosslinked fibrin, using a monoclonal antibody (DD-3B6), latex-bead agglutination assay (DIMERTEST). Seventy-nine of 204 (38.7%) of the preeclamptic women and none of 88 healthy non-preeclamptic women were positive for the D-dimer. Presence of the D-dimer correlated consistently with elevated fibrin(ogen) degradation products, detectable fibrin monomer, and platelet count less than or equal to 100 x 10(9)/L, with a 93.0% sensitivity overall for abnormalities of the same. Among D-dimer-positive women, 66.7% had fibrin(ogen) degradation products less than 10 micrograms/mL, 60.3% had no detectable fibrin monomer, and 82.0% had platelets greater than 100 x 10(9)/L. When compared with D-dimer-negative preeclamptic women, D-dimer-positive women had significantly higher blood pressures prompting delivery, greater proteinuria, more abnormal liver function tests, and higher serum creatinine and blood urea nitrogen. In addition, they had a greater risk of cesarean section (49.4 versus 34.4%), premature delivery (58.2 versus 20.0%), low birth weight (54.5 versus 20.3%), low Apgar scores, and an abnormally high ratio of female to male offspring (1.72 versus 0.93). Testing for the fibrin D-dimer may be useful in early screening and follow-up for preeclamptic coagulopathy, and may also help to define the subset of patients with severe disease. PMID- 2915869 TI - Comparison of late luteal phase endometrial biopsies using the Novak curette or PIPELLE endometrial suction curette. AB - The late luteal phase endometrial biopsy is an important part of the evaluation of patients with recurrent spontaneous abortion or infertility. The procedure can be painful and, if an adequate amount of tissue is not obtained, may have to be repeated. In this report, the results of endometrial biopsies performed in the late luteal phase with either the Novak curette or the PIPELLE Endometrial Suction Curette were analyzed retrospectively. The two techniques did not differ in the number of biopsy specimens found to have inadequate tissue for diagnosis; however, patients who underwent biopsy with the PIPELLE recalled significantly less pain associated with the procedure. When used in premenopausal patients undergoing endometrial biopsy during the late luteal phase, the PIPELE provided adequate tissue with preservation of glandular, stromal, and capsular architecture. PMID- 2915870 TI - Acute intermittent porphyria in pregnancy. AB - A 27-year-old, previously healthy normotensive woman was admitted for hyperemesis gravidarum and treated with intravenous fluids and metoclopramide. Thereafter, a neuropsychiatric syndrome developed, with acute asymmetrical axonal motor-sensory polyneuropathy and marked anxiety, depression, irritability, and memory and concentration difficulties. Raised porphyrin precursors were found in the patient's urine, but not in her feces. Although the association of acute porphyria and pregnancy is rare, the pregnancy itself, combined with a state of starvation, and the administration of metoclopramide, could have precipitated the acute attack in this case. Thiamine deficiency, Guillain-Barre syndrome, and an obstetric complication producing closely related symptoms were excluded. The drug was stopped and the patient was treated with a high-carbohydrate diet and physiotherapy. A normal infant was delivered spontaneously at term. PMID- 2915871 TI - Factor VII deficiency and pregnancy. AB - Hereditary factor VII deficiency is very rare in pregnancy (one in 500,000). However, obstetricians should consider this diagnosis whenever the prothrombin time is prolonged while the activated partial thromboplastin time is normal. The factor VII level increases in normal pregnancy, but the effect of pregnancy upon the factor VII level in deficient individuals is unknown. We report two cases of factor VII deficiency in pregnancy. In both, factor VII levels were 15% or less in the third trimester and were lower postpartum, suggesting that pregnancy does elevate factor VII in deficient individuals as well. Fresh frozen plasma is the treatment of choice. If the level is very low, fresh frozen plasma can be given prophylactically; otherwise, it should be given if blood loss becomes excessive. PMID- 2915872 TI - Protein C deficiency and pregnancy: a case report. AB - Protein C is thought to play a key role in the regulation of hemostasis, and its deficiency has been associated with an increased risk of thromboembolism. Protein C-deficient women are at particular risk of developing thromboembolic complications during pregnancy and delivery. The incidence of thromboembolic events is estimated to be 500-1000 times higher than in normal women. We report the case of a 26-year-old woman with previous iliofemoral deep vein thrombosis who experienced a successful pregnancy and delivery despite severe congenital protein C deficiency (protein C antigen and activity 25%). She was anticoagulated with heparin during the second part of her pregnancy. Our observation suggests that ambulatory full-dose subcutaneous heparin therapy during pregnancy constitutes adequate prevention. However, definite guidelines will require more extensive studies. PMID- 2915873 TI - Bernard-Soulier syndrome complicating pregnancy: a case report. AB - The pregnancy of a patient with Bernard-Soulier syndrome is described. Coagulation abnormalities were encountered, as well as isoimmunization from previous transfusions. Immune suppression was achieved with steroids and intravenous gamma globulin, and plasmapheresis was performed to allow platelet transfusion. PMID- 2915874 TI - Central pontine myelinolysis and pregnancy. AB - Central pontine myelinolysis, also known as osmotic demyelination syndrome, is an uncommon disorder associated with rapid correction of severe hyponatremia. We present the case of a healthy young pregnant woman with hyperemesis gravidarum who developed severe hyponatremia (serum sodium 103 mEq/L). After rapid correction of her serum sodium within 12-15 hours with a 0.9% saline solution, the patient became comatose and died of sepsis and respiratory failure. Examination of the brain showed extensive demyelination in both pontine and extrapontine areas. PMID- 2915875 TI - Recurrent diabetes insipidus associated with pregnancy: pathophysiology and therapy. AB - Diabetes insipidus during pregnancy is an uncommon medical problem. We present a woman who developed transient central diabetes insipidus during two successive pregnancies. A water deprivation study with plasma arginine vasopressin concentrations confirmed the diagnosis and established the efficacy of 1-desamino 8-d-arginine-vasopressin (dDAVP). The patient was then successfully and safely treated through the second pregnancy with dDAVP. PMID- 2915876 TI - Intrapartum uterine rupture. AB - The association between diethylstilbestrol (DES) exposure in utero and uterine malformations resulting in poor reproductive performance is well established. A case is presented of uterine rupture in a patient exposed to DES in utero who had no known predisposing factors for uterine rupture. PMID- 2915877 TI - Postpartum idiopathic brachial neuritis. AB - We present a case of a woman who developed bilateral idiopathic brachial neuritis in the postpartum period following normal pregnancy and delivery. The diagnosis was substantiated with extensive electrophysiologic testing. Shoulder girdle pain and muscular dysfunction resolved slowly, and 12 months later the patient complained only of minimal shoulder discomfort. PMID- 2915878 TI - Ergotism: a possible etiology for puerperal psychosis. AB - Some reports in the medical literature have mentioned the occurrence of psychotic reactions in response to the use of certain ergot alkaloids in therapeutic doses. Prompted by these observations, we undertook a search for cases of "pure" puerperal psychosis (ie, typical manifestations 3-14 days postpartum) in order to evaluate the clinical background of this phenomenon. Special attention was paid to the medications that the patients had received peripartum. In the last 10 years, out of eight perinatal centers, we found only three cases that fulfilled the criteria of the quoted entity. In all instances, the manifestations of puerperal psychosis had been preceded by the administration of ergot derivatives. Based on the presented data, we hypothesize that typical postpartum psychosis may represent an idiosyncratic reaction to potent vasoactive drugs including ergot derivatives. The similarities between the clinical manifestations of ergotism and puerperal psychosis, and some of the epidemiologic features of the latter condition, appear to implicate ergot alkaloids as potential causative agents. Although the validity of the suggested interpretation requires further evaluation, we believe that the currently available data warrant caution with regard to the administration of ergot derivatives postpartum. These drugs should not be used in the absence of clear indication or in unnecessarily high doses. We suggest that ergotism be included in the differential diagnosis in cases of pure puerperal psychosis. PMID- 2915879 TI - Difficulty of fetal monitoring in a fetus with intracardiac tumors. AB - Fetal intracardiac tumors are rare but, when present, are a common cause of poor or uninterpretable fetal heart tracings due to fetal arrhythmias. The most frequently encountered tumor, the rhabdomyoma, is associated with tuberous sclerosis. We present a case demonstrating this difficulty of fetal monitoring in a fetus with an arrhythmia later found to be due to multicentric intracardiac rhabdomyomas. The appropriate evaluation and management of such fetal heart tracings are discussed. PMID- 2915880 TI - Neonatal cranial osteomyelitis: a complication of fetal monitoring. AB - Use of a scalp electrode facilitates and adds precision to electronic fetal monitoring. We report an instance of neonatal osteomyelitis due to infection of the electrode insertion site. Electrode-associated soft and bony tissue infections are most commonly mediated by cervicovaginal microflora and appear clinically and microbiologically distinct from non-electrode-associated cases. Risk assessment, antiseptic care, and observation of the electrode insertion site are recommended. This report emphasizes the potential morbidity of scalp electrode use and suggests means to prevent or mitigate this morbidity. PMID- 2915881 TI - Endometrial reconstruction after hysteroscopic incisional metroplasty. AB - Endometrial reconstruction after hysteroscopic metroplasty of a septate uterus was studied by light microscopy and scanning electron microscopy when the uterus was removed 13 days after metroplasty for a histologic diagnosis of leiomyosarcoma. We observed a retraction of the margins of the incised septum, which could prevent the formation of intrauterine adhesions. Reepithelialization of the cut surface seemed to proceed both centripetally, by proliferation of the surrounding normal endometrium, and centrifugally from the bottom of the glands present at the base of the septum. PMID- 2915882 TI - Familial posterior labial fusion. AB - Partial virilization at birth of a genotypic female resulting in varying degrees of posterior labial fusion and clitoral enlargement is most commonly due to excess androgen production from congenital adrenal hyperplasia. Rarely, labial fusion arises secondary to maternal androgen ingestion or an androgen-secreting tumor during pregnancy. We report a case of posterior labial fusion without clitorimegaly in a 12-year-old girl in which there was no evidence of androgen excess. The family history was remarkable for a similar congenital defect in two aunts and their daughters, suggesting an autosomal dominant trait with incomplete penetrance. PMID- 2915883 TI - Virilizing serous cystadenoma. AB - A 71-year-old woman, 26 years post-menopause, presented with virilization. Facial hirsuties, non-hereditary frontal balding, voice changes, male escutcheon, and mild clitorimegaly accompanied a right adnexal mass. Blood hormone studies showed testosterone 430 ng/dL, FSH 118 mIU/mL, and LH 210 mIU/mL. By ultrasound examination, the cystic adnexal mass involved the right ovary. An 18-cm, 1300-g, unicameral mass with 1200 mL of clear serous fluid and with smooth inner and outer surfaces was removed from the right broad ligament. Intraoperative testosterone levels were as follows: peripheral vein 285 ng/dL, left ovarian vein 301 ng/dL, and right ovarian vein 1635 ng/dL; tumor cystic fluid was 3032 ng/dL. Peripheral vein testosterone was 15 ng/dL 3 days postoperatively. Histopathologically, the tumor was a serous cystadenoma. No evidence of stromal luteinization, hyperplasia, or inflammation was found, and other virilizing lesions were not encountered in either ovary or in other tissues. Epithelial cells constituting the tumor may have been the source of the excess testosterone in this unique case of virilizing serous cystadenoma. PMID- 2915884 TI - Successful treatment of a prolactin-producing pituitary macroadenoma with intravaginal bromocriptine mesylate: a novel approach to intolerance of oral therapy. AB - A 37-year-old woman with a symptomatic 18-mm prolactin-secreting pituitary adenoma could not be managed with oral bromocriptine mesylate because of unacceptable gastrointestinal side effects. However, when given the medication intravaginally, the patient was successfully treated as assessed by evident tumor shrinkage and diminished secretory activity. Serum bromocriptine levels were approximately six to eight times higher than those reported after oral administration. The vaginal route may help reduce some of the adverse effects of bromocriptine mesylate experienced during oral administration and may possibly allow lowering of the overall effective dose by avoiding first liver passage. PMID- 2915885 TI - Meigs syndrome and elevated CA 125. AB - A patient presented with a pelvic mass, ascites, and pleural effusion. The serum CA 125 level was noted to be 226 U/mL (normal 5-35 U/mL). On surgical exploration, she had a benign fibroma-thecoma without malignant cytology in the ascitic fluid. Postoperatively, the pleural effusion resolved and the CA 125 decreased to 32 U/mL. This is the first reported case of Meigs syndrome and an elevated CA 125 level. As previously documented, elevated serum CA 125 does not always indicate malignancy. PMID- 2915886 TI - Double-J ureteral catheters in gynecologic surgery. AB - When ureteral injury is identified and properly managed, the gynecologic surgeon can expect good surgical and functional results with little or no patient discomfort or morbidity. The double-J silicone ureteral catheter is a useful surgical tool in this situation. The diameter of the ureteral catheter should be 7 or 8 French in most gynecologic surgical settings. It is better to select a length that is several centimeters too long. Intraoperative and postoperative care, including extraperitoneal drainage of the operative site, antibiotics, transurethral bladder drainage, and selection of the duration of urinary diversion, is important for a good outcome. PMID- 2915887 TI - 5-Fluorouracil, adriamycin, cyclophosphamide (FAC) vs. 5-fluorouracil, epirubicin, cyclophosphamide (FEC) in metastatic breast cancer. AB - 94 evaluable patients with metastatic breast cancer were randomly assigned to 5 fluorouracil, adriamycin, and cyclophosphamide (FAC) or 5-fluorouracil, epirubicin, and cyclophosphamide (FEC), with cycles repeated every 3 weeks. The objective response rate to FAC was 46% versus 44% to FEC. There was no significant difference in the median duration of response and median survival for the two regimens. Toxicity was more frequent and more pronounced in patients receiving FAC. Results indicate therapeutic equivalence of the two regimens and reduced toxicity of the epirubicin arm. PMID- 2915888 TI - Factors influencing local recurrence after curative surgery for rectal cancer. AB - The histories of 90 consecutive patients who underwent curative surgery for rectal cancer from January 1975 to December 1981 were reviewed. Twenty of 90 patients (22.2%) recurred locally. The site of the primary lesion and tumor differentiation are the most important factors influencing local recurrence. Median survival from recurrence was 3 months and no patient was alive after 15 months. No significant difference in survival was observed in patients surgically treated for recurrence compared to untreated patients. PMID- 2915890 TI - Anticipatory nausea and vomiting: prevalence and predictors in chemotherapy patients. AB - One hundred and seventy-five patients selected at random were prospectively studied. All patients were assessed at least after the first cycle of treatment by a self-report questionnaire which covered the occurrence of nausea and vomiting 24 before chemotherapy, as well as information regarding 22 clinical parameters. Forty-six (26%) patients developed anticipatory nausea. 'Intolerable' posttreatment vomiting and age under 45 were statistically significant parameters (p less than 0.05) in the multivariate analysis. Twenty-one (12%) of the 175 patients experienced anticipatory vomiting. Three variables, age under 45, 'intolerable' posttreatment vomiting and more than three cycles of treatment were found to be significant (p less than 0.05). The relative risk of developing anticipatory nausea and vomiting according to combination of significant clinical predictors in the multivariate analysis is proposed. Therefore recognition of these clinical predictors may serve as a marker for patients with high risk of presenting anticipatory nausea and vomiting, who may benefit from prophylactic behavioral approaches. PMID- 2915889 TI - Biochemical classification of circulating immune complexes in human malignant melanoma and hematologic neoplasms. AB - Circulating immune complexes (CIC) in human cancer are known to be very heterogeneous in size and composition. In 95 staged malignant melanoma patients and 71 individuals with leukemia and lymphoma, this heterogeneity was analyzed biochemically in sera positive for CIC. CICs were measured by a multiassay system and individual complexes were isolated and analyzed by immunological and biochemical methods. Analyses of sera from 100 normal individuals, from 25 rheumatoid women, and a group of 12 laboratory staff who work with human melanoma were included for comparison. Three basic patterns of complexes were identified circulating in the sera of the cancer patients. Type I are medium-sized (17-23S), complement-fixing complexes usually occurring in combinations. The prototype in melanoma contained IgG antibody and additional glycoprotein components and bound complement by the classical pathway. In hematological malignancies four subtypes could be identified depending on whether the antibody class was IgG or IgM, the nonimmunoglobulin component was glycoprotein or protein, and whether complement fixation occurred by the classical or alternate pathway. Type II complexes were noncomplement-fixing, medium-sized complexes (15-21S), which in melanoma contained IgG antibody and additional protein components. In the hematologic malignancies two subtypes could be identified depending on whether the antibody class was IgG or IgM. Both subtypes contained a glycoprotein nonimmunoglobulin component. Both melanoma and hematologic tumors had type III heavy complexes (36 44S) which were noncomplement-fixing and contained only immunoglobulin components, either IgG-IgG or IgM-IgG. As expected the rheumatoid arthritis patients frequently had both 7S and 21-23S CICs containing IgG as well as IgM rheumatoid factor with complement fixation via the classical pathway. No CICs were detected in normal young men and women (20-30 years); a few individuals in middle age (31-50 years) had small (7-11S) CICs which bound complement by the classical pathway and contained IgG and a protein nonimmunoglobulin component. The frequency of these 7S complexes increased with advancing age, with the appearance of 23S IgG-IgG or IgM-IgG complexes. IgG antibodies from only the melanoma patients reacted with cytoplasmic components of fresh melanoma cells, except the laboratory workers where all of their isolated CIC antibodies also reacted with melanoma cells. Thus the heterogeneity of complexes in melanoma is not random, but can be classified into three basic biochemical patterns. The hematologic group provides a slightly richer variation of subtypes within this basic scheme. PMID- 2915891 TI - Iliac crest needle biopsy as a method for determining estrogen receptors in bone metastases from breast cancer. AB - The purpose of our study was to clarify whether the amount of tissue extracted by means of iliac crest needle biopsy (ICNB) would suffice for a quantitative determination of estrogen receptors (ER) in bone metastases, and to see if the method currently used for determining ER in primary tumors could also be successfully utilized in ICNB. 22 of 31 breast cancer patients examined could be evaluated. ER was positive in 7 (31.8%). Reasonable data are to be expected when the biopsy weight exceeds 0.1 g. Our study confirms that the necessary amount of tissue for ER analysis can indeed be extracted by ICNB. Our results justify further studies on a larger group of patients, since we cannot make conclusive statements concerning the value of this method for predicting the ultimate success of an endocrine treatment. PMID- 2915892 TI - Clinical significance of paraneoplastic syndrome. AB - The prevalence, clinical presentations, and diagnostic significance of the paraneoplastic syndrome (PNS) in the setting of a department of internal medicine in a community hospital was studied. During a 7-year period (1979-1985) a total of 167 patients among 11,000 hospitalized patients were diagnosed as having a malignant neoplasia previously unknown. From this group we selected all cases who presented with one or more of the known clinical PNSs. Forty-two cases, i.e., 25% fulfilled the selection criteria. Their prevalence in our population was higher than usually found in the literature. Sixteen different categories of PNS were observed. They occurred 55 times, since more than one PNS was present in 9 cases. No significant correlation was observed between any type of PNS and any particular class of malignant neoplasia. At the time of initial evaluation, PNSs were associated with stage I malignancy in 15 cases, with stages II and III in 8 and 3 cases, respectively, and with stage IV in 22 cases. PNSs were the leading symptom or sign in 56% of the patients. In these patients the PNS determined the direction of work-up in the search for a malignant tumor. However, PNSs were essential for suspecting cancer in stage I of the disease in 6 cases only, i.e., 14%. We stress that awareness of the clinical implications of these syndromes may permit an earlier diagnosis of malignancy. PMID- 2915893 TI - Paraneoplastic hypercalcemia in endometrial carcinoma. AB - Humoral hypercalcemic syndrome associated with tumors of the female reproductive system is believed to be uncommon, and only 27 such cases have been identified prior to 1980. We describe 2 patients with humoral hypercalcemia in clear cell adenocarcinoma of the uterus, and review the literature on previously published cases. Both our patients fulfilled the criteria for humoral hypercalcemic syndrome, namely: hypercalcemia without bone metastases ranging from 12.8 to 14.1 mg/dl in the presence of normal serum parathyroid hormone levels, reduced tubular reabsorption of phosphate, and reduced serum albumin. We propose that humoral hypercalcemia is perhaps not a rare complication of uterine malignancy and, that increased awareness may result in early diagnosis of this important metabolic problem. PMID- 2915894 TI - Application of DA/DAPI technique in cancer cytogenetics. AB - The recent advent of banding techniques has facilitated the identification of human chromosomal abnormalities in neoplasias. Utilization of a single technique for the identification of marker chromosomes has caused ambiguity because staining profiles overlap with many other chromosomal regions in the human genome. Thus, the implication of DA/DAPI technique in clinical cytogenetics has been documented by presenting a variety of cases with neoplastic syndromes. PMID- 2915895 TI - Carcinogenic effect of biscuits made of flour infested with Tribolium castaneum in Bufo regularis. AB - Biscuits made of flour infested with Tribolium castaneum induced the formation of hepatocellular carcinomas (22%) when force-fed to toads (Bufo regularis) at a dose level of 200 mg/50 g 3 times a week. Maximal time of exposure and observation was 16 weeks. Some metastatic deposits from the primary liver tumours were found in the kidneys. Thus, the carcinogenic potency of the biscuits was almost the same as that of the flour previously reported by the authors indicating that the temperature of the oven in which the biscuits were baked did not alter the carcinogenicity of the infested flour. PMID- 2915896 TI - [Postoperative lymph node scintigraphy in patients with malignant melanoma]. AB - Completeness of regional lymph node dissection was controlled in 23 patients with melanoma malignum. For that purpose 3--6 weeks after block-dissection lymph node scintigraphy was performed, by administration of intercostal and interdigital radiopharmacutical. Blockdissection was considered as complete, when neither after intercostal, nor after interdigital administration, any lymph nodes were delineated. On the basis of investigations until now, postoperative lymph node scintigraphy proves to be suitable, held to be a non-invasive method for controlling completeness of blockdissection. PMID- 2915897 TI - [Diffuse intestinal malignant lymphoma]. AB - The authors describe a patient with malignant lymphoma presenting with clinically severe malabsorption due to diffuse involvement of the small intestine and with intestinal obstruction. The histologic diagnosis was based on the association of (1) diffuse involvement of the small intestine showing lymphoid tissue expansion and (2) a non-classified form of highly malignant lymphoma. After surgical resection of a stenotic part of the small intestine, abdominal irradiation therapy was done, and the patient improved. PMID- 2915898 TI - [The effect of carbamazepine on water metabolism in epileptics]. PMID- 2915899 TI - Proto-oncogene abnormalities in human breast cancer: c-ERBB-2 amplification does not correlate with recurrence of disease. AB - The incidence of c-ERBB-2 amplification in breast cancers and its usefulness as a predictor of tumor recurrence after treatment have been subjects of controversy (Ali et al., 1988, Slamon et al., 1987). We re-examined this subject by analysing 157 primary and 14 metastatic breast cancers with c-ERBB-2 and 18 other molecular probes as controls. Five proto-oncogenes were found to be occasionally amplified in primary breast cancers: c-ERBB-2 (11%), c-MYB (3%), c-RAS-Ki (3%), INT-2 (4%) and c-MYC (6%). No statistically significant correlation between amplification of c-ERBB-2 and recurrence of tumors was observed. The only significant correlation observed was between early recurrence of advanced (stage III) tumors and amplification of one or another of the above five proto-oncogenes. We conclude that breast cancer utilize multiple genetic mechanisms in their progression and metastasis, and that analysis of c-ERBB-2 alone is not a useful guide. PMID- 2915900 TI - HER-2 amplification, steroid receptors and epidermal growth factor receptor in primary breast cancer. AB - Amplification of HER-2 oncogene was analysed in DNAs obtained from 291 primary human mammary carcinomas. 52/291 (18%) were found to contain amplified HER-2 oncogene. Moderate amplification (2- to 5-fold) was noted in 36/291 (12%). Thirteen tumors (4.5%) had a copy number of 5 to 10. A 10- to 20-fold and greater than 20-fold amplification was observed in 2 and 1 patient, respectively. Sample sizes allowed the determination of estrogen receptor (ER) and progesterone receptor (PgR) levels in 253/291 primary breast cancers. HER-2 gene amplification was noted in 14% of ER+ patients and in 28% of ER- patients, respectively (P = 0.02). Similarly a significantly greater number of PgR- primary mammary carcinoma exhibited an amplification of the HER-2 gene compared to PgR+ cases (22% vs. 16%, P = 0.01). Although statistically not significant, tumors with HER-2 gene amplification were found to have lower levels of ER and PgR. No association of HER-2 amplification with the androgen receptor and EGF receptor was observed. Present data combine to suggest that tumor progression is more stringently controlled by the oncogene upon loss of hormone dependency. Differences found in HER-2 amplification between steroid receptor positive and negative tumors could be helpful to define a specific subset of women to whom adjuvant therapy should be directed. PMID- 2915901 TI - Nucleotide sequence of a cDNA encoding TIS11, a message induced in Swiss 3T3 cells by the tumor promoter tetradecanoyl phorbol acetate. AB - We report here the nucleic acid sequence and deduced amino acid sequence of a cDNA for TIS11, a gene induced in 3T3 cells by tetradecanoyl phorbol acetate. PMID- 2915902 TI - Transcription activation by serum, PDGF, and TPA through the c-fos DSE: cell type specific requirements for induction. AB - We have investigated the sequences that are necessary and sufficient for the induction of the c-fos gene by serum, TPA or PDGF in different cell types. The dyad symmetry element (DSE) is a regulatory element of the c-fos gene previously shown to be required for induction of c-fos transcription by serum. We show that the DSE is also necessary for the induction of c-fos by either TPA or PDGF in NIH3T3 cells. We also show that in NIH 3T3 cells the DSE is sufficient to confer inducibility on a heterologous promoter, the beta-globin promoter, when serum provides the stimulus. However, it is not sufficient when either TPA or PDGF is the inducer. This suggests a requirement in 3T3 cells for cooperating sequence elements for TPA or PDGF induction but not for serum. Interestingly, the need for cooperating elements for TPA induction is abolished in HeLa cells since the DSE alone is sufficient for TPA inducibility of the beta-globin promoter in these cells. Thus, the highly transformed HeLa cell line displays diminished sequence requirements for TPA induction. We discuss the possibility that mutations which diminish the stringent transcriptional control of protooncogenes such as c-fos may contribute to the transformed state. PMID- 2915903 TI - The amplification unit on chromosome 11q13 in aggressive primary human breast tumors entails the bcl-1, int-2 and hst loci. AB - The int-2 gene, a member of the fibroblast growth factor (FGF) super-gene family, has previously been shown to be amplified in 16% of the 110 human breast tumors examined. In order to characterize the amplification unit containing the int-2 gene (chromosome 11q13), the same panel of breast tumors was screened for possible amplifications of other markers mapping between 11q11 and 11q24. Out of the eight additional genes analysed, simultaneous amplification of bcl-1 (11q13, a locus involved in hematopoietic malignancies) and hst (11q13, another member of the FGF family) was observed in 17/18 tumors with increased copy number of the int-2 gene. A single breast tumor showed amplification of int-2 oncogene only. Neither the bcl-1 nor the hst locus was individually amplified in any of the tumor DNAs examined. PMID- 2915904 TI - Alternative 5' end of the bcr-abl transcript in chronic myelogenous leukemia. AB - Philadelphia chromosome positive acute lymphocytic leukemia and chronic myelogenous leukemia are strongly associated with two distinct forms of bcr-abl chimeric protein, known as P190 and P210, respectively. By studying cDNA clones obtained from the cell line KBM-5, we identified two new bcr-abl transcripts. These are formed by alternative splicing of at least two exons to the known bcr exon 2. One novel transcript can encode a protein kinase of approximately 190 kd, while the other can direct the synthesis of a larger protein whose amino terminus remains to be defined. The alternative exons can be spliced also to the two normal bcr transcripts, reflecting the activation of a cryptic promoter. These messages were present at low abundance in two cases of blastic crisis but were not detected in the chronic phase. It is conceivable that the proteins encoded by the new bcr-abl mRNAs are involved in the transformation to the acute phase in some cases of chronic myelogenous leukemia. PMID- 2915905 TI - Tips of the trade #8. A goniometer for acetabular positioning. AB - Dislocations following total hip replacement continue to be a small but persistent problem. Most authors believe one of the major causes is a malposition of the femoral head and/or acetabular component. We have developed a simple goniometer that positions on the face of the acetabular component and reads a crude but helpful position of the prosthesis both in lateral tilt and anteversion. PMID- 2915907 TI - Orthopaedics Overseas #15. Project Ethiopia. AB - This paper presents the highlights of a month invested as a volunteer at Tikur Anbessa Hospital, Addis Ababa, Ethiopia. PMID- 2915906 TI - Pain clinic #12. The use of a self-administration system for oral analgesics on an orthopaedic service. AB - The use of patient-controlled analgesia systems in the postoperative period has become quite popular over the past several years. The systems to date have been limited to analgesics administered intravenously. The purpose of this study was to extend the use of a patient-controlled analgesia system to include oral analgesics during a patient's hospital stay. PMID- 2915908 TI - Approaches to senior care #6. Shoulder pain in the geriatric patient. Part I. Evaluation and pathophysiology. AB - Shoulder pain is one of the most common musculoskeletal complaints in the elderly. The rewards of accurate diagnosis and early treatment often elude the orthopaedist without a systematic approach to this region. A thorough understanding of shoulder anatomy, pain referral patterns, and the pathophysiology of the aging process must be combined with an awareness of the latest treatment modalities and surgical techniques. PMID- 2915909 TI - Orthopaedics overseas: the other side of the coin. PMID- 2915910 TI - Imaging rounds #97. Salter II fracture of the proximal tibia. AB - Proximal tibial physeal injury is extremely rare. It occurs most often in adolescents and is the result of a significant abduction force applied to the lower leg with the foot firmly fixed. Management of this injury follows the same principles as other Salter-Harris epiphyseal plate fractures. Prognosis is generally good, although there is a somewhat higher than anticipated incidence of angulatory and longitudinal deformities of Type I and Type II fractures, much as has been observed in distal femoral physeal fractures. This is probably due to direct injury to the germinal layer of the growth plate with subsequent partial physeal closure. PMID- 2915911 TI - Surgical disassembly of the Sivash hip. AB - Due to the constrained nature of the Sivash type total hip, revision of the acetabular component without revision of the stem depends on the ability to separate the unit. Where the stem is tight in the shaft of the femur, it is preferable not to revise the stem if separation of the components is possible. This report describes a simple method of component separation. PMID- 2915912 TI - UCI/RAM total knee arthroplasty: a ten-year review. AB - This study covers a ten-year period of UCI/RAM total knee arthroplasty (Dow Corning-Wright). Two hundred twenty-nine knees out of 516 done during this period were evaluated in an office setting. Additionally, 70 mail responses were obtained, and 52 patients were found to be deceased. This gives a 68% followup of all cases done during this period. Surgical technique, postoperative course, functional results, and complications are reviewed. PMID- 2915913 TI - A study of glenohumeral orientation in patients with anterior recurrent shoulder dislocations using computerized axial tomography. AB - Thirty-six patients with recurrent anterior shoulder dislocations and 11 normal patients who had no history of shoulder problems were evaluated by a G.E. 8800 fourth generation computerized axial tomographer to quantitate humeral head retrotorsion and glenoid tilt. The study objective was to determine if osseous orientation was a major etiologic factor in patients with recurrent anterior shoulder dislocations. The normal position of the humeral head as determined by CT scan is 30 degrees retroversion with respect to its distal articular axis. In dislocations this value changes to a more anteverted position of 24 degrees retroversion. Glenoid tilt could not be given a single value since it changes from retroversion superiorly toward more anteversion inferiorly. This change in glenoid tilt was greater in the dislocators with inferior sections measuring 2 degrees anteversion in the dislocators and 1 degree retroversion in the uninvolved shoulder and in the normal population. The change in humeral retroversion and glenoid tilt in the recurrent dislocators was statistically significant when compared with the uninvolved shoulder and to the normal population. Thus, the glenoid humeral orientation appears to be a significant predisposing factor to recurrent anterior shoulder dislocations. PMID- 2915914 TI - Congenital gluteus maximus contracture. AB - Muscle contractures are infrequent in Israel. This report discusses one case of a congenital contracture associated with a skin dimple treated in Israel. A 3-year old boy presented with difficulty in running, riding a bicycle, and squatting. Flexion of the right hip in adduction was impossible. The hip could be fully flexed in abduction. Congenital contracture of the right gluteus maximus muscle was successfully treated by surgical release. PMID- 2915915 TI - Pitfalls in diagnosis: the hip. AB - The hip joint is unique anatomically, physiologically, and developmentally. Because of these features, diagnosis of pathologic conditions is more difficult than for most joints. Because delay in diagnosis and treatment may result in crippling osteoarthritis, it is imperative that diagnostic pitfalls be avoided. PMID- 2915916 TI - Management of congenital hip dysplasia. AB - In summary, congenital hip dysplasia remains a worldwide health problem, which has not been resolved by neonatal screening programs. The primary care physician's role is critical for early diagnosis. An understanding of the need for repeated examinations, the age related signs, and continued diligence is essential. The common use of the triple diaper treatment is not recommended. PMID- 2915917 TI - Pitfalls in fractures. PMID- 2915918 TI - Phospholipase C sensitive FVII activity and FVII antigen in hypertriglyceridemia. AB - An increase in factor VII coagulant activity (FVIIc) was found in patients with high thrombotic risk and in hyperlipidemias, namely in Fredrickson's types IIb and IV. This elevation was correlated with the level of total cholesterol and triglyceride concentrations. It has been suggested that this increase is due to higher FVII coagulant activity related to the formation of a complex between factor VII (FVII) and phospholipids, since it was shown that FVIIc returns to normal levels after incubation of plasma with phospholipase C. In this respect we have studied the activity of FVII before and after phospholipase C plasma treatment and FVII related antigen (FVIIag) in patients with types IIa, IIb and IV hyperlipidemias. An elevation of FVIIc was found in hyperlipidemic patients compared to normal controls. FVIIag values were also higher in type IV patients, implicating an increase in FVII total concentration and not only an activation of FVII. Furthermore, Phospholipase C action on patients' plasma samples lowered FVIIc to levels very similar to those of FVIIag. In normal controls the same action was noted and it seems therefore likely that the proposed phospholipid contribution to FVIIc hyperactivity plays only a minor role in FVII changes in primary hyperlipidemia. Instead, FVIIag increase seems to be the major mechanism of FVII increase in primary hypertriglyceridemic patients. PMID- 2915919 TI - Are most secondary acute lymphoblastic leukemias mixed acute leukemias? AB - A case of acute lymphoblastic leukemia (ALL) secondary to X-ray exposure is reported. The lymphoblasts expressed T-cell and myelomonocytic differentiation related surface antigens. Clonal chromosomal abnormalities including t(2;12)(q25;q13),-10,der(10), del(11)(q14),der(12) and r were observed. A review of the cytogenetic data suggests that most secondary ALLs, with the exception of Burkitt type ALLs, may be biphenotypic or mixed acute leukemias. PMID- 2915920 TI - Microgranular acute promyelocytic leukemia: a proposed role for a greater deformability of the leukemic cell. AB - A case of microgranular acute promyelocytic leukemia (APL), M-3 variant, is reported in a boy aged 5 years. The disease, which was rapidly fatal, presented with acute disseminated intravascular coagulation (DIC) and leukocytosis. Different cytomorphologic subtypes of promyelocytes were identified on the basis of cytoplasmic granular patterns: the microgranular type with barely visible cytoplasmic granulations and deeply basophilic cytoplasm and the more characteristic type with large promyelocytes containing azurophil granules. We observed a ratio of large promyelocytes to microgranular promyelocytes of 1:1.2 in the marrow and 1:4 in the peripheral blood. To explain this discrepancy, we hypothesize that the microgranular promyelocytes may be more deformable than the typical promyelocyte and that this intrinsic cellular characteristic may promote marrow egress and increase the likelihood of hyperleukocytosis in the M-3 variant. PMID- 2915921 TI - DNA bending and binding factors of the human beta-actin promoter. AB - Transcription of the beta-actin gene is rapidly inducible in response to serum stimulation. To determine the regions responsible for serum inducible and basal level expression, the human beta-actin promoter was subjected to mutational analysis. Two distinct elements, the CCAAT homology and the beta-actin specific conserved sequences, were found by a chloramphenicol acetyltransferase expression assay and sequence comparisons, and then analyzed for possible functions. Using a DNA bend assay, it was shown that the conserved sequences included the core of a sequence-directed bend of DNA. Gel mobility shift and DNase I protection assays revealed that the conserved sequences and the CCAAT homology were recognized by binding factors in HeLa cell extracts. PMID- 2915922 TI - Replication timing of 10 developmentally regulated genes in Physarum polycephalum. AB - We have tested the hypothesis which stipulates that only early-replicating genes are capable of expression. Within one cell type of Physarum - the plasmodium - we defined the temporal order of replication of 10 genes which were known to be variably expressed in 4 different developmental stages of the Physarum life cycle. Southern analysis of density-labeled, bromodesoxyuridine-substituted DNA reveals that 4 genes presumably inactive within the plasmodium, were not restricted to any temporal compartment of S-phase: 1 is replicated in early S phase, 2 in mid S-phase and 1 in late S-phase. On the other hand, 4 out of 6 active genes analysed are duplicated early, with the first 30% of the genome. Surprisingly, the two others active genes are replicated late in S-phase. By gene dosage analysis, based on quantitation of hybridization signals from early and late replicating genes throughout S-phase, we could pinpoint the replication of one of these two genes at a stage where 80-85% of the genome has duplicated. Our results demonstrate that late replication during S-phase does not preclude gene activity. PMID- 2915923 TI - Rat mammary gland fatty acid synthase: localization of the constituent domains and two functional polyadenylation/termination signals in the cDNA. AB - The rat fatty acid synthase (FAS) is active only as a dimer, although the eight component functions are contained in a single polypeptide chain. Using mRNA from lactating rat mammary glands a cDNA expression library was established. With the overlapping immunologically positive clones we have an 8.9kb cDNA sequence for rat FAS. In the 3'-nontranslated region of the rat FAS cDNA we find a prototype polyadenylation/termination signal and 779 nucleotides upstream, a mutated one. Both of these polyadenylation/termination signals are used and give rise to two equally abundant mRNA species which are coordinately regulated. In the derived amino acid sequence we could locate six of the eight component functions; their order is NH2- beta-ketoacyl synthase - acetyl/malonyl transferases -enoyl reductase - acyl carrier protein - thioesterase -COOH. Comparison of FAS from different sources shows that the primary sequence is conserved only for the active residues and the amino acids in their immediate vicinity. PMID- 2915924 TI - Regulation of the human beta-actin promoter by upstream and intron domains. AB - We have identified three regulatory domains of the complex human beta-actin gene promoter. They span a region of about 3000 bases, from not more than -2011 bases upstream of the mRNA cap site to within the 5' intron (832 bases long). A distal upstream domain contains at least one enhancer-like element. A proximal upstream domain, with a CArG [for CC(A + T rich)6GG] motif found in all known mammalian actin genes, seems to confer serum, but not growth factor, inducibility. The third domain is within the evolutionarily conserved 3' region of the first intron and contains a 13 base-pair sequence, identical to the upstream sequence with the CArG motif. This domain also contains sequences that are both serum and fibroblast growth factor inducible. PMID- 2915925 TI - Thymidylate synthase gene expression is stimulated by some (but not all) introns. AB - We previously described the construction of an intronless mouse thymidylate synthase (TS) minigene that has the normal 5' and 3' flanking regions of the gene linked to full length TS cDNA. Transfection of the minigene into ts- hamster V79 cells led to low level expression of normal mouse TS mRNA and protein. In the present study we analyzed the effect of introns on the expression of the TS minigene in transient transfection assays. Inclusion of introns 5 and 6 at their normal locations in the coding region led to an 8-9-fold stimulation of the level of TS and TS mRNA. Almost all of introns 5 and 6 could be deleted without diminishing the stimulatory effect. Inclusion of intron 3 also stimulated the expression of the minigene, although to a lesser extent than introns 5 and 6. However, inclusion of intron 4 had no stimulatory effect. Analysis of minigenes that contained various combinations of introns revealed that the stimulatory effects of the introns were not additive. PMID- 2915926 TI - Excess information at bacteriophage T7 genomic promoters detected by a random cloning technique. AB - In our previous analysis of the information at binding sites on nucleic acids, we found that most of the sites examined contain the amount of information expected from their frequency in the genome. The sequences at bacteriophage T7 promoters are an exception, because they are far more conserved (35 bits of information content) than should be necessary to distinguish them from the background of the Escherichia coli genome (17 bits). To determine the information actually used by the T7 RNA polymerase, promoters were chemically synthesized with many variations and those that function well in an in vivo assay were sequenced. Our analysis shows that the polymerase uses 18 bits of information, so the sequences at phage genomic promoters have significantly more information than the polymerase needs. The excess may represent the binding site of another protein. PMID- 2915927 TI - Compensatory mutations demonstrate that P8 and P6 are RNA secondary structure elements important for processing of a group I intron. AB - Compensatory mutations have been constructed which demonstrate that P8 and P6, two of nine proposed base-pairing interactions characteristic of group I introns, exist within the folded structure of the Tetrahymena thermophila rRNA intervening sequence, and that these secondary structure elements are important for splicing in E. coli and self-splicing in vitro. Two-base mutations in the 5' and 3' segments of P8 are predicted to disrupt P8 and a strong splicing-defective phenotype is observed in each case. A compensatory four-base mutation in P8 is predicted to restore pairing, and results in the restoration of splicing activity to nearly wild type levels. Thus, we conclude that P8 exists and is essential for splicing. In contrast to the strong phenotypes generally exhibited by mutations which disrupt RNA secondary structure, a two-base mutation in L8, the loop between P8[5'] and P8[3'], results in only a slight decrease in splicing activity. We also tested P6, a pairing which is proposed to consist of only two base-pairs in this intron. A two-base mutation in P6[3'] reduces splicing activity to a greater extent than does a two-base mutation in P6[5']. Comparison of the activities of these mutants and a compensatory P6 four-base mutant support the existence of P6, and suggest that the P6 pairing may be particularly important in the exon ligation step of splicing. PMID- 2915928 TI - Construction of mutant and chimeric genes using the polymerase chain reaction. AB - In the polymerase chain reaction (PCR) the specific amplification of a small segment of DNA within a complex DNA sample is effected by repeated cycles of DNA denaturation and enzymatic synthesis primed by two oligonucleotides complementary to regions within opposite strands of the DNA. In this report a simple and efficient method is described in which PCR methodology is used to introduce specific mutations into a double stranded DNA molecule. In this procedure a supercoiled plasmid DNA serves as template for a PCR in which a primer bearing the mutated sequence is incorporated into the amplified product. The presence of convenient restriction sites in the mutagenic primer and in the amplified DNA permit direct replacement of a wild type DNA segment with the mutated segment by treating the PCR mixture with the appropriate restriction endonucleases followed by DNA ligase. Using this procedure, a single amino acid replacement, a 16 amino acid deletion and a replacement of four amino acids with a twelve amino acid segment from another membrane protein were introduced into the amino terminal signal segment of rat hepatic cytochrome P450b (P450IIB1). PMID- 2915930 TI - Nucleotide sequence of two mouse histone H4 genes. PMID- 2915929 TI - Transcriptional activation of Xenopus class III genes in chromatin isolated from sperm and somatic nuclei. AB - Xenopus sperm chromatin lacks class III transcription complexes and somatic histone H1. Inactive class III genes in sperm chromatin are easily programmed with transcription complexes de novo and transcribed in Xenopus oocyte nuclear extract. In contrast, repressed class III genes in somatic chromatin are not transcribed in the oocyte nuclear extract. Class III genes that are initially inactive or repressed in both types of chromatin can be efficiently transcribed in a cell free preparation of Xenopus eggs. Chromatin mediated repression of class III genes in somatic nuclei is reversible in Xenopus egg extract, but not in the oocyte nuclear extract. Any inhibition of transcription attributed to chromatin assembly onto a gene, will therefore depend on the extract in which transcription is assayed. PMID- 2915931 TI - Nucleotide sequence of a 25S rRNA gene from tomato. PMID- 2915932 TI - The complete nucleotide sequence of bovine liver cytochrome b5 mRNA. PMID- 2915933 TI - The tRNAglu (anticodon TTU) gene and its upstream sequence coding for a homolog of the E. coli large ribosome-subunit protein L14 in the Tetrahymena mitochondrial genome. PMID- 2915934 TI - Improved control of partial DNA restriction enzyme digest in agarose using limiting concentrations of Mg++. PMID- 2915935 TI - Preparation of single stranded insert DNA free of vector sequences. PMID- 2915936 TI - Direct recovery of in vitro transcripts in a protected form suitable for prolonged storage and shipment at ambient temperatures. PMID- 2915937 TI - Oncogene detection by enzymatic amplification on flow sorted chromosomes. PMID- 2915938 TI - Construction of representative genomic DNA libraries using one microgram of DNA. PMID- 2915939 TI - Increased efficiency of the Taq polymerase catalyzed polymerase chain reaction. PMID- 2915940 TI - The use of nickel-titanium alloy in orthopedic surgery in China. AB - A new biomaterial made of nickel and titanium with its shape-memory characteristics has been manufactured, investigated, and used in Shanghai, China. Since 1981, this biomaterial has been used in 265 cases clinically, among which 71 involved orthopedic surgery. Results are satisfactory without failure in our short-term follow up. This preliminary report of the use of this new biomaterial with the unique characteristic of being able to recover to its original shape with particular transformation temperatures indicates its potential for opening a new field for investigation in surgery. Research to discover appropriate ratios of nickel and titanium for specific usage is underway. The interest and cooperation between the medical and engineering professions may eventually solve the problems through mutual efforts and result in improved shape-memory biomaterials. PMID- 2915941 TI - Tire explosion injuries. AB - Twenty-five patients hospitalized with injuries sustained from tire explosions from 1980 to 1987 were reviewed. Injuries occurred directly from the tire rim or parts of its assembly, from the patient being thrown against adjacent unyielding structures, or a combination of these. Lethal or life-threatening injuries do occur, so these patients initially must be triaged as polytrauma patients. Resuscitation and expeditious attention to life-threatening injuries must be provided when necessary. Serious head, facial, eye, and upper extremity injuries occurred frequently. Pelvic and long-bone fractures, particularly those of the femur, are stabilized primarily as part of the overall treatment of the polytraumatized patient. Open fractures and fractures with arterial injuries and/or compartment syndromes are primarily decompressed, debrided, and appropriately stabilized. After life-threatening and limb-threatening injuries are attended, eye injuries that threaten sight should be addressed. While hand, wrist, and other upper extremity injuries that do not fall in the above categories may not require immediate or primary treatment, they are often critical in determining the patient's final outcome. This is particularly true since most patients are manual workers, often mechanics. Therefore, hand, wrist, and upper extremity injuries should be treated as early as possible and in parallel with other injuries to achieve optimal results and minimize impairment, disability, and time and economic loss from work. Strong emphasis should be placed on education and safety training in preventing this severe form of civilian trauma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2915942 TI - Interlocked intramedullary nailing of the humerus. AB - Indications for use of the intramedullary interlocked humeral nail are: pathologic fractures, including those with severe osteopenia alone; nonunions, especially those with bone atrophy and/or marked osteopenia; and humeral shaft fractures with comminution, bone loss, or other causes of instability not controlled by conventional treatment methods. In this series, eight patients were treated by intramedullary interlocked humeral nail. Follow up ranged up to 30 months, with an average of 12 months. Five of six patients in this series who had the potential to unite their fractures did so. The remaining patient had a painless fibrous union. While the two patients with pathologic fractures of the humeral shaft caused by malignant tumors did not unite their fractures, the pain relief, functional recovery, and lack of postoperative morbidity justified the operative procedure. PMID- 2915943 TI - Distal radial osteotomy. AB - Malunions of distal radius fractures are commonplace. Patients are decreasingly willing to accept the disability that may be associated with them. While the first line of treatment is initial good fracture care, corrective osteotomies offer later opportunity for pain relief and improved function. PMID- 2915944 TI - The use of the Manuflex disposable mini external fixator. AB - The Manuflex mini external fixator is an original device which is suitable for either provisional or definitive fixation of hand or foot fractures. The system is simple, disposable, relatively radiolucent, and inexpensive. It has been tested in an animal laboratory and has been used successfully in 27 human cases. PMID- 2915945 TI - Bone strength of the radius and ulna in the non-human primate. AB - The technique and measurement of the bone strength of the radius and ulna in the non-human primate are presented. The aim of this study was to find a relationship between the mechanical strength of an intact radius and ulna forearm and its collateral isolated radius and isolated ulna which would be of assistance in the studies on mechanical bone strength and bone healing. The findings include: (1) bone strength is significantly influenced by factors such as age, sex, and body weight; (2) wide variation in normal bone-tissue strength exists among similar individuals; (3) there are differences in bone strength in the same individual if contralateral sides are compared; (4) growing bones are very elastic and are able to bend to an angle of up to 90 degrees before a fracture occurs; (5) soft tissue structures (such as muscle, interosseous membrane, and tendons) do not contribute to the strength of a diaphysis in low velocity injuries; and (6) the midshaft area of the radius is approximately 10% stronger than that of the ulna in the adult. PMID- 2915946 TI - Surgical techniques of a radioulnar transposition. PMID- 2915947 TI - The biomechanics and biology of internal fixation using plates and nails. AB - In fracture healing, the mechanical environment and bone biology are closely related. Furthermore, the mechanics of the medullary nail fixation are, in many aspects, different from those of compression fixation using screws and plates. A few general items will be discussed to review the basic principles of the mechanics and biology involved and to clarify the terminology. This article outlines the basic ideas of mechanical and biological interaction. PMID- 2915948 TI - The use of a clamp-on plate for forearm fractures. AB - A clamp-on plate has been developed to stabilize long-bone diaphyseal fractures. Its design is entirely different from conventional screw-secured plates. Minimal soft tissue, especially periosteal, dissection is required for application. Since there is no intramedullary encroachment, no further damage is done to the endosteal blood supply. One hundred seventy-one fractures of the radius and/or ulna were followed for at least 6 months. There were no nonunions. The average time to union was 12.3 weeks, compared to 21.4 weeks for similarly selected fractures of the radius and/or ulna treated during the same time framework by conventional screw-secured plating methods. The fact that union is reliable and can be achieved earlier than with conventional screw-secured plates supports the author's contention that sparing of the blood supply to the fracture and thus, the biological integrity of fracture healing play a parallel role along with biomechanical stability in achieving fracture union. PMID- 2915949 TI - The treatment of displaced metaphyseal fractures with screws and wiring systems. AB - Within the context of modern fracture fixation, buttress plates have traditionally played an important role in stabilizing both intraarticular and extraarticular displaced metaphyseal fractures. While plating has substantially improved the assurance of union and functional recovery in these fractures, there is some interference with physiologic blood supply to the regions of the fracture and, consequently, to the biological elements of healing. This article outlines alternative methods of treatment for these fractures using screws and wiring systems with little, if any, loss of stability. Patients must be selected carefully and must have large fracture fragments and normal or near normal mineralization of their bones. When screw and wiring methods can be used, there is less tissue dissection and, consequently, less interference with the physiologic fracture healing process. PMID- 2915950 TI - Open reduction and internal fixation of three-part fractures of the proximal humerus. AB - Eleven patients with 12 three-part fractures of the proximal humerus were treated by open reduction and internal fixation using AO/ASIF buttress plating. All of the fractures healed. There were no failures of fixation. Nine of these patients returned for a follow up of more than 2 years and had a satisfactory rating using Neer's shoulder rating system. Five patients who had an acromioplasty at the time of their initial surgery had slightly better function and range of motion than the remaining patients. Successful operative treatment requires accurate definition of the fracture pattern, careful attention to the details of internal fixation, and supervised postoperative rehabilitation. PMID- 2915951 TI - Implant materials for fracture fixation: a clinical perspective. AB - The optimum management of traumatic skeletal fractures may involve the installation of high quality surgical implants by a skilled orthopedic surgeon. Satisfactory clinical results are very dependent on the ability to maintain stable fracture fixation. Well designed contemporary implants rely on precise control of material composition and properties to achieve a well tolerated level of biological response. Metallic materials, such as 316L stainless steel, pure titanium, and titanium alloys, demonstrate an acceptable combination of strength, ductility, corrosion resistance, and biocompatibility. Polymers, composites, and biodegradable materials may offer selected opportunities for fracture fixation. An understanding of relevant clinical factors is essential to evaluate potential applications for advanced materials. PMID- 2915952 TI - Metallurgical evaluation of retrieved implants and correlation of failures to patient record data. AB - This study sought to establish an orthopedic implant retrieval program according to ASTM F561-87 (the American Society for Testing and Materials) and to describe the results of evaluation of failed implants. A total of 275 fracture fixation and prosthetic devices have been retrieved to date. Results of metallurgical evaluation showed no deviations in ASTM specifications among the failed implants evaluated. The cause of failure in most cases was fatigue following nonunion or delay in healing. PMID- 2915953 TI - The malpractice mess. Bodies don't come with a guarantee. PMID- 2915954 TI - Physiologic changes as patients get older. AB - As the population ages, primary care physicians are treating increasing numbers of elderly patients. Although certain physiologic changes are known to be age related, they do not occur uniformly in elderly persons, and it may be difficult to distinguish signs of normal aging from those of disease. Thus, individualized care is important, and with thoughtful diligence, primary care physicians can often improve the quality of life for their elderly patients. PMID- 2915955 TI - Choice of antibiotic for lower urinary tract infections in men. AB - When lower urinary tract infection is present in a male patient, prostatic involvement must be considered. A 30-day course of treatment with one of the antibiotics shown to be superior in treating prostatitis is recommended. It is hoped that this program will eliminate needless progression or relapse of infection and reduce the subsequent risk for development of chronic prostatitis. PMID- 2915956 TI - The MD bureaucrats of PROs. PMID- 2915957 TI - Removing broken needles and other foreign objects. AB - A needle or other foreign body that has penetrated the skin superficially can be located and removed fairly easily. If it is too deeply embedded to be palpated, it should be located by use of an image intensifier and two venipuncture needles. If this is unsuccessful, exploration and removal must be done in the operating room. PMID- 2915958 TI - Unexplained right hilar mass. AB - A right hilar mass was found on a computed tomographic (CT) scan in a 40-year-old man who presented with fever, sore throat, and general malaise. Initial testing ruled out various bacterial and viral infections and carcinoma. The patient's condition continued to deteriorate, and the mass as seen on repeat CT scan increased in size. Surgical biopsy of sections of the right lower lobe confirmed the diagnosis of histoplasmosis. Most histoplasmosis infections are asymptomatic, and even those that are not are usually self-limited and require only observation. When treatment is required, ketoconazole (Nizoral) now provides a less toxic alternative to amphotericin B (Fungizone). PMID- 2915959 TI - Why we won't use an AIDS vaccine. PMID- 2915960 TI - Oral trauma. Emergency care of lacerations, fractures, and burns. AB - Emergency physicians are usually the first to see patients with injuries to oral and facial tissues. Because many of these patients may have life-threatening neurologic injuries, secondary oral and perioral problems may be overlooked initially. These injuries, however, have a profound potential for causing lifelong disability and disfigurement and should be addressed as soon as the patient's condition stabilizes. It is essential to diagnose and manage these problems effectively in the emergency setting and then to make prompt direct referral to an appropriate specialist when the patient's condition permits. PMID- 2915961 TI - Leukemia-associated skin infiltrates. PMID- 2915962 TI - Delayed diagnosis of herpes zoster. AB - Herpes zoster may cause diagnostic confusion and mimic other diseases during the early stage before development of the characteristic rash. Although the disease is usually self-limited, oral acyclovir (Zovirax) shows promise in reducing the duration and severity of symptoms in uncomplicated cases. PMID- 2915963 TI - Do you think ... routine immunotherapy is useful for asthma patients? PMID- 2915964 TI - Anemia in the elderly. Symptoms, causes, and therapies. AB - Anemia is common in the elderly, but it is not a normal manifestation of aging and should be evaluated as it would be in a younger person. History taking, physical examination, assessment of red cell morphology, and simple laboratory evaluations (ie, reticulocyte count, iron studies, vitamin levels, sometimes bone marrow examination) usually elucidate the cause. Hypoproliferation of red cells is the most common form of anemia in the elderly, caused more often by chronic disease or iron deficiency and less often by vitamin deficiencies or bone marrow infiltration. Anemia with an elevated reticulocyte count, seen less often in the elderly, suggests acute blood loss or hemolysis. In some patients, the cause is not obvious, and anemia is likely due to increased sensitivity of the hematopoietic system to multiple insults and decreased homeostatic reserve. Transfusions should be used judiciously in patients with symptomatic anemia who are likely to benefit from increased oxygen delivery after transfusion. PMID- 2915965 TI - The dizzy patient. A practical approach to management. AB - Dizziness can generally be divided into true vertigo and pseudovertigo (giddiness or light-headedness). The most common causes of pseudovertigo are hyperventilation, orthostatic hypotension, and multisensory deficits of older patients. Of the many types of true vertigo, only a few are caused by serious structural disorders of the brainstem, and these can usually be recognized by their temporal profile and concomitant symptoms and signs. Most cases of vertigo are caused by peripheral vestibular disorders that are self-limiting. Treatment is directed toward control of the acute autonomic symptoms and labyrinthine suppression until physiologic compensation takes place. Patients with vertigo that is prolonged, chronic, and recurrent may be helped by exercises designed to hasten or assist recovery of compensatory mechanisms. PMID- 2915966 TI - Extracorporeal shock wave lithotripsy for gallstones. How effective is it? AB - The Food and Drug Administration has approved an investigational trial of biliary lithotripsy in the treatment of cholesterol gallstones. Preliminary results from Germany indicate that lithotripsy followed by oral bile acid medication results in the disappearance of the disintegrated gallstones in more than 90% of patients in one to two years. The procedure is an alternative to surgery for patients with cholesterol gallstones. The outpatient treatment and early resumption of normal activities are in contrast to the lengthy hospitalization and recovery required with cholecystectomy. PMID- 2915967 TI - The health insurance mess. Less for more! PMID- 2915968 TI - Flexible fiberoptic sigmoidoscopy. Important screening tool for colorectal disorders. AB - Because of the frequency of colorectal disease and the effectiveness of early intervention in the polyp-cancer sequence, surveillance for this problem should be a routine part of health-maintenance examinations. The general use of flexible sigmoidoscopy in conjunction with fecal occult blood screening is an extremely important part of healthcare delivery. Flexible sigmoidoscopy can easily be learned by most physicians. If use of the procedure becomes widespread, the effects of colorectal disease, in terms of both patient suffering and healthcare costs, can be reduced. PMID- 2915969 TI - Managing the dry eye. Accurate diagnosis is the key. AB - In patients with symptoms of dry eye, a complete patient history and thorough clinical examination are necessary to determine the exact cause. Laboratory and histologic studies provide supportive evidence of the diagnosis. Treatments include the correction of anatomic abnormalities, protecting the eye from the environment, use of artificial tears and ointments, lid hygiene, punctal occlusion, and tarsorrhaphy. When inflammatory or immunologic processes are involved, local and systemic immunosuppression may be indicated. PMID- 2915970 TI - Dental emergencies. Management by the primary care physician. PMID- 2915971 TI - Magnetic resonance imaging versus computed tomography--which one? AB - Both magnetic resonance imaging (MRI) and x-ray computed tomography (CT) are essential diagnostic imaging tools in current practice. The main goal of this article is to provide a quick reference guide to help the busy clinician choose which test to obtain first to avoid the need for a second expensive imaging examination. In general, MRI is preferred for examination of the CNS, the spine for disk disease, major joints, and soft tissues of the extremities. CT is preferred for examination of the head and spine after acute trauma and of the chest, abdomen, and pelvis. PMID- 2915972 TI - A 5' splice-region G----C mutation in exon 1 of the human beta-globin gene inhibits pre-mRNA splicing: a mechanism for beta+-thalassemia. AB - We have characterized a Mediterranean beta-thalassemia allele containing a sequence change at codon 30 that alters both beta-globin pre-mRNA splicing and the structure of the hemoglobin product. Presumably, this G----C transversion at position -1 of intron 1 reduces severely the utilization of the normal 5' splice site since the level of the Arg----Thr mutant hemoglobin (designated hemoglobin Kairouan) found in the erythrocytes of the patient is very low (2% of total hemoglobin). Since no natural mutations of the guanine located at position -1 of the CAG/GTAAGT consensus sequence had been isolated previously, we investigated the role of this nucleotide in the constitution of an active 5' splice site by studying the splicing of the pre-mRNA in cell-free extracts. We demonstrate that correct splicing of the mutant pre-mRNA is 98% inhibited. Our results provide further insights into the mechanisms of pre-mRNA maturation by revealing that the last residue of the exon plays a role at least equivalent to that of the intron residue at position +5. PMID- 2915973 TI - Growth restriction of influenza A virus by M2 protein antibody is genetically linked to the M1 protein. AB - The M2 protein of influenza A virus is a 97-amino acid integral membrane protein expressed at the surface of infected cells. Recent studies have shown that a monoclonal antibody (14C2) recognizes the N terminus of M2 and restricts the replication of certain influenza A viruses. To investigate the mechanism of M2 antibody growth restriction, 14C2 antibody-resistant variants of strain A/Udorn/72 have been isolated. Most of the variant viruses are not conventional antigenic variants as their M2 protein is still recognized by the 14C2 antibody. A genetic analysis of reassortant influenza viruses prepared from the 14C2 antibody-resistant variants and an antibody-sensitive parent virus indicates that M2 antibody growth restriction is linked to RNA segment 7, which encodes both the membrane protein (M1) and the M2 integral membrane protein. Nucleotide sequence analysis of RNA segment 7 from the variant viruses predicts single amino acid substitutions in the cytoplasmic domain of M2 at positions 71 and 78 or at the N terminus of the M1 protein at residues 31 and 41. To further examine the genetic basis for sensitivity and resistance to the 14C2 antibody, the nucleotide sequences of RNA segment 7 of several natural isolates of influenza virus have been obtained. Differences in the M1 and M2 amino acid sequences for some of the naturally resistant strains correlate with those found for the M2 antibody variant viruses. The possible interaction of M1 and M2 in virion assembly is discussed. PMID- 2915975 TI - Individual microglia move rapidly and directly to nerve lesions in the leech central nervous system. AB - Small cells called microglia, which collect at nerve lesions, were tracked as they moved within the leech nerve cord to crushes made minutes or hours before. The aim of this study was to determine whether microglia respond as a group and move en masse or instead move individually, at different rates, and whether they move along axons directly to the lesion or take another route, such as along the edges of the nerve cord. Cell nuclei in living nerve cords were stained with Hoechst 33258 dye and observed under dim ultraviolet illumination using fluorescence optics, a low-light video camera, and computer-assisted signal enhancement. Muscular movements of the cord were selectively reduced by bathing in 23 mM MgCl2. Regions of nerve cord within 300 microns of the crush were observed for 2-6 hr. Only a fraction of microglia, typically less than 50%, moved at any time, traveling toward the lesion at speeds up to 7 microns/min. Cells were moving as soon as observation began, within 15 min of crushing, and traveled directly toward the lesion along axons or axon tracts. Movements and roles of leech microglia are compared with their vertebrate counterparts, which are also active and respond to nerve injury. PMID- 2915974 TI - Topology of cell adhesion molecules. AB - The neural cell adhesion molecule (N-CAM) exists in two major forms [ld (large cytoplasmic domain) peptide and sd (small cytoplasmic domain) peptide] that contain transmembrane segments and different cytoplasmic domains and in a third form [ssd (small surface domain) peptide] that lacks transmembrane and cytoplasmic regions. All forms have the same extracellular region of more than 600 amino acid residues, a region also found in a fragment (Fr2) that can be released from cells by proteolysis. The liver cell adhesion molecule (L-CAM) is expressed as a single species that is distinct from N-CAM, but its extracellular region can also be obtained as a proteolytic fragment (Ft1). Examination of the various forms of N-CAM and the Ft1 fragment of L-CAM by electron microscopy of rotary shadowed molecules indicated that they all have rod-shaped structures that contain a hinge region which is apparently flexible. Both the ssd chain and the Fr2 fragment of N-CAM are single rods bent into arms approximately 18 and 10 nm long. The ld and sd chains are longer bent rods that form rosettes comprising two to six branches; detergent treatment disrupts these rosettes into single rods. Specific antibodies that block homophilic N-CAM binding labeled the distal ends of the branches of the ld/sd rosettes and the ends of the longer arm of both the ssd chain and the Fr2 fragment. Antibodies that bind to the sialic acid-rich region of N-CAM bound near the hinge. These data indicate that the N-CAM rosettes are formed by interaction between their transmembrane or cytoplasmic domains and not by interactions involving their homophilic binding sites. The L-CAM Ft1 fragment is also a bent rod with an apparently flexible hinge; like the ssd chain and the Fr2 fragment of N-CAM, it does not form aggregates. The similarities between L-CAM and N-CAM, despite their differences in amino acid sequence, suggest that their general configuration and the presence of a flexible hinge are important elements in assuring effective and specific cell-cell adhesion. PMID- 2915976 TI - Alpha-helix and mixed 3(10)/alpha-helix in cocrystallized conformers of Boc-Aib Val-Aib-Aib-Val-Val-Val-Aib-Val-Aib-OMe. AB - Two molecules of Boc-Aib-Val-Aib-Aib-Val-Val-Val-Aib-Val-Aib-OMe (where Boc is t butoxycarbonyl and Aib is alpha-aminoisobutyryl) cocrystallize in a triclinic cell with different helical conformations. One molecule is completely alpha helical with seven 5----1 intramolecular hydrogen bonds. It forms three head-to tail NH...O = C hydrogen bonds to other molecules of the same conformation. The second molecule has a mixed 3(10)/alpha-helix conformation with three 4----1 hydrogen bonds and four 5----1 hydrogen bonds; furthermore, there is a helix reversal at both termini. The second molecule forms only two head-to-tail hydrogen bonds with molecules of the same type, and the N(3)H group does not participate in any hydrogen bonding. The two different types of helices occur in alternate sheets in the crystal, where each sheet is composed of adjacent rods of helices formed by head-to-tail hydrogen bonding. Within each sheet, containing helices of only one type of conformation, the helices aggregate in a parallel mode. Between the sheets of different helices, the aggregation is antiparallel. The peptide, with formula C51H92N10O13, crystallizes in space group P1 with Z = 2 and cell parameters a = 10.047 +/- 0.002 A, b = 16.684 +/- 0.003 A, c = 19.198 +/ 0.004 A, alpha = 80.30 degrees +/- 0.01 degrees, beta = 85.74 degrees +/- 0.01 degrees, and gamma = 83.03 degrees +/- 0.01 degrees; overall agreement factor R = 6.7% for 6053 data ([F0] greater than 3 sigma) and 0.96-A resolution. PMID- 2915977 TI - Inhibitor of hematopoietic pluripotent stem cell proliferation: purification and determination of its structure. AB - We report here a five-step purification procedure that led to the isolation from fetal calf bone marrow extract of a tetrapeptide, Ac-Ser-Asp-Lys-Pro (Mr 487), exerting a high inhibitory activity on the proliferation of hematopoietic pluripotent stem cells [defined here as spleen colony-forming units (CFU-S)]. The structure of this molecule was established from amino acid analysis, fast atom bombardment mass spectrometry, and 1H nuclear magnetic resonance spectral data. This structure was confirmed by comparison with the corresponding synthetic molecule, which presents identical physiochemical characteristics and biological properties. Natural and synthetic peptides administered to mice (at a dose of 100 ng per mouse) after one injection of cytosine arabinonucleoside prevent CFU-S recruitment into DNA synthesis. PMID- 2915978 TI - Expression of delta-aminolevulinate synthase in avian cells: separate genes encode erythroid-specific and nonspecific isozymes. AB - A controversy has existed in the literature for the past several years regarding the number of vertebrate genes encoding the mitochondrial protein that initiates the first step in heme biosynthesis, delta-aminolevulinate synthase [ALAS; succinyl-CoA: glycine C-succinyltransferase (decarboxylating), EC 2.3.1.37]. By analysis of chicken ALAS cDNA clones isolated from both liver and erythroid cells, we show that at least two separate genes encode ALAS mRNAs. These experiments show that (i) two different genes encode the ALAS isozymes found in erythroid and in liver tissues, and (ii) while the product of the erythroid gene (ALASE) is expressed exclusively in erythroid cells, the hepatic form of the enzyme is expressed ubiquitously, suggesting that this is the nonspecific form (ALASN) found in all chicken tissues. PMID- 2915979 TI - Purification and characterization of a newly identified growth factor specific for epithelial cells. AB - A growth factor specific for epithelial cells was identified in conditioned medium of a human embryonic lung fibroblast cell line. The factor, provisionally termed keratinocyte growth factor (KGF) because of its predominant activity on this cell type, was purified to homogeneity by a combination of ultrafiltration, heparin-Sepharose affinity chromatography, and hydrophobic chromatography on a C4 reversed-phase HPLC column. KGF was both acid and heat labile and consisted of a single polypeptide chain of approximately 28 kDa. Purified KGF was a potent mitogen for epithelial cells, capable of stimulating DNA synthesis in quiescent BALB/MK epidermal keratinocytes by greater than 500-fold with activity detectable at 0.1 nM and maximal at 1.0 nM. Lack of mitogenic activity on either fibroblasts or endothelial cells indicated that KGF possessed a target cell specificity distinct from any previously characterized growth factor. Microsequencing revealed an amino-terminal sequence containing no significant homology to any known protein. The release of this growth factor by human embryonic fibroblasts raises the possibility that KGF may play a role in mesenchymal stimulation of normal epithelial cell proliferation. PMID- 2915980 TI - Cytosolic components of the respiratory burst oxidase: resolution of four components, two of which are missing in complementing types of chronic granulomatous disease. AB - The respiratory burst oxidase of neutrophils can be activated in a cell-free system in which plasma membranes, cytosol, Mg2+, and a membrane-perturbing detergent, such as arachidonate or sodium dodecyl sulfate, are all required. Using the technique of preparative isoelectric focusing, the cytosol factor required for oxidase activation was resolved into four components termed C1-C4 with respective pI values of approximately 3.1, 6.0, 7.0, and 9.5. Individually, these components were incapable of activating the oxidase and could only be detected in the presence of suboptimal amounts of normal cytosol that served to supply at least a limited amount of each of the required components. Attempts to activate the oxidase with a combination of the four components failed, suggesting that there might be a yet undetected fifth cytosolic component. Patients with autosomal recessive cytochrome b-positive chronic granulomatous disease (type II CGD) are severely deficient in cytosol factor activity. When added to cytosol samples from two patients with this form of CGD, component C4 restored the ability of each patient's cytosol to activate dormant oxidase. None of the other three cytosol factor components (C1-C3) was effective in this regard, a finding supported by the direct demonstration that these three components were present in normal amounts in this type of CGD. A different form of type II CGD was identified in a third patient on the basis of complementation studies in which the patient's cytosol was able to activate the oxidase in the cell-free system when mixed with cytosol from one of the first two patients. The defect in this third patient's cytosol could be partially corrected by component C2, but not component C4, obtained from normal cytosol. These findings indicate that the role of cytosol in the activation of the respiratory burst oxidase is more complex than previously appreciated in that at least four cytosolic components appear to be required. Defects in two of these components have now been identified and appear to be responsible for two biochemically distinct forms of CGD. PMID- 2915981 TI - Identification of androgen receptors in normal human osteoblast-like cells. AB - The sex steroids, androgens and estrogens, are major regulators of bone metabolism. However, whether these hormones act on bone cells through direct or indirect mechanisms has remained unclear. A nuclear binding assay recently used to demonstrate estrogen receptors in bone [Eriksen, E.F., Colvard, D.S., Berg, N.J., Graham, M.L., Mann, K.G., Spelsberg, T.C. & Riggs, B.L. (1988) Science 241, 84-86] was used to identify specific nuclear binding of a tritiated synthetic androgen, [3H]R1881 (methyltrienolone), in 21 of 25 (84%) human osteoblast-like cell strains and a concentration of bound steroid receptors of 821 +/- 140 (mean +/- SEM) molecules per cell nucleus. Binding was saturable and steroid-specific. Androgen receptor gene expression in osteoblasts was confirmed by RNA blot analysis. Relative concentrations of androgen and estrogen receptors were compared by measuring specific nuclear estrogen binding. Nuclear binding of [3H]estradiol was observed in 27 of 30 (90%) cell strains; the concentration of bound estradiol receptor was 1537 +/- 221 molecules per cell nucleus. The concentrations of nuclear binding sites were similar in males and females for both [3H]R1881 and [3H]estradiol. We conclude that both androgens and estrogens act directly on human bone cells through their respective receptor-mediated mechanisms. PMID- 2915982 TI - Estrogen receptor selectively binds the "coding strand" of an estrogen responsive element. AB - An initial step in the transcriptional activation of the prolactin gene by estrogen is the binding of the estrogen-receptor complex to a specific nucleotide sequence [estrogen responsive element (ERE)]. Using the gel mobility assay, we examined the binding mechanism of purified estrogen receptor to the ERE contained on a 255-base-pair fragment from the upstream region between nucleotides -1784 to -1531 of the rat prolactin gene. Remarkably, specific high-affinity binding was detected to the dissociated "coding strand" but not to the "noncoding strand" of the ERE-containing fragment. The dissociated strands of this fragment possess unusual secondary structure, as indicated by their anomalous migration in the gel mobility assay. The estrogen receptor binds to the coding strand of the ERE with a 60-fold higher affinity than to the double-stranded ERE. Furthermore, the receptor binds with a 1000-fold greater affinity to the coding strand of the ERE than to a double-stranded nonspecific DNA fragment. We propose that, in vivo, the estrogen receptor initially binds to the double-stranded ERE. Subsequently, the DNA strands separate due to transitory strand separation and supercoiling, allowing folding of the coding strand of the ERE into a structure that is then bound more tightly by the receptor. The formation of this receptor-ERE coding strand complex may be a crucial step in the mechanism of estrogen-stimulated transcription. PMID- 2915983 TI - Inhibition of growth of nonbasal planes in ice by fish antifreezes. AB - Peptide and glycopeptide antifreezes from a variety of cold-water fishes cause ice single crystals grown from the melt to assume unusual and strikingly similar habits. The antifreezes inhibit growth on the prism faces but allow limited growth on the basal plane. As new layers are deposited on the basal plane, pyramidal surfaces develop on the outside of the crystal, and large hexagonal pits form within the basal plane. The pits are rotated 30 degrees with respect to the normal orientation of hexagonal ice crystals. Growth inhibition on the prism, pyramidal, and pit faces indicates that these faces contain sites of adsorption of the antifreeze molecules. Several properties of the antifreeze pits are consistent with (but do not prove) an origin of the pits at dislocations. The similarity of crystal habit imposed on ice by antifreezes with wide differences in composition and structure indicates a common mechanism. PMID- 2915984 TI - Effect of mutations on the binding and translocation functions of a chloroplast transit peptide. AB - We studied transport and binding to intact chloroplasts of 10 mutants in three regions of the transit peptide of a precursor to the small subunit of ribulose 1,5-bisphosphate carboxylase/oxygenase [3-phospho-D-glycerate carboxy-lyase (transphosphorylating), E.C.4.1.1.39]. Transport was assayed in a reconstituted system using isolated pea chloroplasts and radioactively labeled precursor. Binding to the chloroplast envelope was assayed in a similar manner using chloroplasts pretreated with nigericin. Most mutants showed a dramatically decreased capacity of binding, although some of them transported relatively well. The accumulation of the mutant proteins inside the chloroplast as a function of time was examined. Although the authentic small subunit precursor was imported rapidly, uptake of most mutant precursors was considerably slower and continued until the last time point examined. In terms of assigning functions to individual regions, we found that at least the middle region and parts of the amino and the carboxyl termini of the transit peptide are more important for receptor binding than for translocation. A two-step processing mechanism has been postulated for the maturation of the small subunit precursor. This model predicts the occurrence of processing intermediates. When precursors carrying carboxyl-terminal deletions were presented to the chloroplast, no defined intermediates could be detected. Instead, a number of proteins, probably resulting from aberrant processing, accumulated simultaneously inside the chloroplasts. PMID- 2915985 TI - Isolation of a complementary DNA encoding a chitinase with structural homology to a bifunctional lysozyme/chitinase. AB - An extracellular, acidic chitinase was purified to homogeneity from tobacco necrosis virus-infected leaves of Cucumis sativis. The amino acid sequences of the intact protein and of peptides isolated following endoproteinase Lys-C digestion, cyanogen bromide cleavage, and trypsin digestion were determined. Oligonucleotide probes derived from this sequence were used to isolate a cDNA clone encoding this protein. No significant homology was found between this chitinase and either the basic chitinase isolated from bean or tobacco or the chitinase isolated from Serratia marcescens; however, strong homology was found between the cucumber chitinase and a lysozyme/chitinase from Parthenocissus quinquifolia. The induction of the protein by tobacco necrosis virus infection or salicylate was found to be at the level of RNA accumulation. Genomic Southern analysis indicates that a single gene in the cucumber genome encodes this protein. PMID- 2915986 TI - Evidence that autophosphorylation of solubilized receptors for epidermal growth factor is mediated by intermolecular cross-phosphorylation. AB - Structurally distinguishable mutants of human epidermal growth factor receptor (EGFR) were used to investigate the mechanism of EGFR autophosphorylation. Mutant receptors generated by site-directed mutagenesis were expressed in transfected NIH 3T3 cells lacking endogenous receptors. After coincubation of cell lysates in the presence or absence of EGF, receptor immunoprecipitates were incubated with [gamma-32P]ATP. A kinase-negative mutant EGFR (K721A), in which Lys-721 in the ATp binding site was replaced by an alanine residue, was shown to be phosphorylated in an EGF-dependent manner by an enzymatically active EGFR deletion mutant lacking two autophosphorylation sites. A mutant EGFR lacking the EGF-binding domain as well as the phosphorylation sites also phosphorylated the kinase-negative mutant. In both cases the kinase-negative mutant K721A was phosphorylated on sites virtually identical to the sites that are autophosphorylated by wild-type recombinant or native human EGFRs. With four different site-specific anti-EGFR antibodies, it was shown that deletion mutants devoid of epitopes recognized by the antibodies were coimmunoprecipitated together with wild-type or mutant receptors recognized by the antibodies. This indicates that EGFR oligomers were preserved during immunoprecipitation. On the basis of these results, we propose that autophosphorylation of solubilized EGFR is mediated by intermolecular cross-phosphorylation, probably facilitated by receptor oligomerization. PMID- 2915987 TI - Species distribution of a phosphoprotein (parafusin) involved in exocytosis. AB - A cytosolic phosphoprotein that appears to function in membrane fusion during exocytosis of secretory products has previously been isolated from Paramecium tetraurelia. This phosphoprotein, parafusin, with Mr 63,000, is rapidly dephosphorylated via a Ca2+-dependent process when secretagogues induce exocytosis in competent cells. Dephosphorylation does not occur in exocytosis incompetent cells. Polyclonal antibodies against purified parafusin have now been used to show that this protein is present in unicellular organisms and cells of metazoan groups of wide evolutionary divergence, such as yeast, insects, and mammals, including humans. These results suggest that parafusin was present early in the history of eukaryotes and that it is of functional importance in the general mechanism of exocytosis and membrane fusion. PMID- 2915988 TI - Synthesis and characterization of a model extracellular matrix that induces partial regeneration of adult mammalian skin. AB - Regeneration of the dermis does not occur spontaneously in the adult mammal. The epidermis is regenerated spontaneously provided there is a dermal substrate over which it can migrate. Certain highly porous, crosslinked collagen glycosaminoglycan copolymers have induced partial morphogenesis of skin when seeded with dermal and epidermal cells and then grafted on standard, full thickness skin wounds in the adult guinea pig. A mature epidermis and a nearly physiological dermis, which lacked hair follicles but was demonstrably different from scar, were regenerated over areas as large as 16 cm2. These chemical analogs of extracellular matrices were morphogenetically active provided that the average pore diameter ranged between 20 and 125 microns, the resistance to degradation by collagenase exceeded a critical limit, and the density of autologous dermal and epidermal cells inoculated therein was greater than 5 x 10(4) cells per cm2 of wound area. Unseeded copolymers with physical structures that were within these limits delayed the onset of wound contraction by about 10 days but did not eventually prevent it. Seeded copolymers not only delayed contraction but eventually arrested and reversed it while new skin was being regenerated. The data identify a model extracellular matrix that acts as if it were an insoluble growth factor with narrowly specified physiochemical structure, functioning as a transient basal lamina during morphogenesis of skin. PMID- 2915989 TI - Identification of the structural mutation responsible for the dibucaine-resistant (atypical) variant form of human serum cholinesterase. AB - A point mutation in the gene for human serum cholinesterase was identified that changes Asp-70 to Gly in the atypical form of serum cholinesterase. The mutation in nucleotide 209, which changes codon 70 from GAT to GGT, was found by sequencing a genomic clone and sequencing selected regions of DNA amplified by the polymerase chain reaction. The entire coding sequences for usual and atypical cholinesterases were compared, and no other consistent base differences were found. A polymorphic site near the C terminus of the coded region was detected, but neither allele at this locus segregated consistently with the atypical trait. The nucleotide-209 mutation was detected in all five atypical cholinesterase families examined. There was complete concordance between this mutation and serum cholinesterase phenotypes for all 14 heterozygous and 6 homozygous atypical subjects tested. The mutation causes the loss of a Sau3A1 restriction site; the resulting DNA fragment length polymorphism was verified by electrophoresis of 32P labeled DNA restriction fragments from usual and atypical subjects. Dot-blot hybridization analysis with a 19-mer allele-specific probe to the DNA amplified by the polymerase chain reaction distinguished between the usual and atypical genotypes. We conclude that the Asp-70----Gly mutation (acidic to neutral amino acid substitution) accounts for reduced affinity of atypical cholinesterase for choline esters and that Asp-70 must be an important component of the anionic site. Heterogeneity in atypical alleles may exist, but the Asp-70 point mutation may represent an appreciable portion of the atypical gene pool. PMID- 2915990 TI - Isolation of two alleles of the b locus of Ustilago maydis. AB - The basidiomycete Ustilago maydis is the causative agent of the disease corn smut. To be pathogenic, strains of U. maydis must be heterozygous for a locus called "b," which appears to control both pathogenicity and sexual development. Two alleles of the b locus of U. maydis were isolated by complementation and hybridization. The clones have the specificities of b1 and b2 alleles as demonstrated by their effects on the colony morphology and pathogenicity of haploid and diploid strains upon transformation. For example, nonpathogenic haploid and diploid strains of U. maydis carrying b2 alleles became pathogenic when transformed with the cloned b1 allele. Furthermore, an a2 b2 haploid strain could be transformed to an a2 b1 genotype by gene replacement using a DNA fragment containing a b1 allele and a selectable marker. The isolation of b alleles represents an important step toward understanding the control of dicaryon formation, dicaryon maintenance, and pathogenicity in U. maydis. PMID- 2915991 TI - Molecular patterns of X chromosome-linked color vision genes among 134 men of European ancestry. AB - We used Southern blot hybridization to study X chromosome-linked color vision genes encoding the apoproteins of red and green visual pigments in 134 unselected Caucasian men. One hundred and thirteen individuals (84.3%) had a normal arrangement of their color vision pigment genes. All had one red pigment gene; the number of green pigment genes ranged from one to five with a mode of two. The frequency of molecular genotypes indicative of normal color vision (84.3%) was significantly lower than had been observed in previous studies of color vision phenotypes. Color vision defects can be due to deletions of red or green pigment genes or due to formation of hybrid genes comprising portions of both red and green pigment genes [Nathans, J., Piantanida, T.P., Eddy, R.L., Shows, T.B., Jr., & Hogness, D.S. (1986) Science 232, 203-210]. Characteristic anomalous patterns were seen in 15 (11.2%) individuals: 7 (5.2%) had patterns characteristic of deuteranomaly (mild defect in green color perception), 2 (1.5%) had patterns characteristic of deuteranopia (severe defect in green color perception), and 6 (4.5%) had protan patterns (the red perception defects protanomaly and protanopia cannot be differentiated by current molecular methods). Previously undescribed hybrid gene patterns consisting of both green and red pigment gene fragments in addition to normal red and green genes were observed in another 6 individuals (4.5%). Only 2 of these patterns were considered as deuteranomalous. Thus, DNA testing detected anomalous color vision pigment genes at a higher frequency than expected from phenotypic color vision tests. Some color vision gene arrays associated with hybrid genes are likely to mediate normal color vision. PMID- 2915993 TI - Electrophysiologic study of rabbit proximal tubular cell monolayers in primary culture. AB - Primary cultures of renal cortical cells prepared by selective sieves have been found to display some characteristics of renal proximal tubular epithelium but their site of origin has not been confirmed by electrophysiologic studies. Cells were cultured in a defined medium on collagen gels. Confluency was approached after 7-10 days but gels were found to have zero transepithelial resistance unless they were allowed to contract spontaneously. With the appearance of a nonzero resistance, there was a change in morphology to a more columnar cell with better developed microvilli. These structural features were particularly prominent in clusters of proliferating cells observed on and around remnants of original tubules embedded in the gel. In noncontracted cultures there was no focal cell clustering and cells were squamous-like with rudimentary microvilli, similar in appearance to cells grown on plastic culture dishes. Measurements made in contracted monolayers yielded an average transepithelial resistance of 6.5 omega cm2, a spontaneous transepithelial potential difference of +0.9 mV, measured with respect to the serosa, and an apical membrane potential of -75 mV when cells were bathed in 0.4 mM K and -49 mV when cells were bathed in 4 mM K media. Mucosal protamine (50 micrograms/ml) increased transepithelial resistance by 22%, suggesting that the epithelial cell tight junctions were responsive to external stimuli. Monolayers were anion selective, giving a dilution potential (lumen-directed NaCl gradient) of -2.6 mV with respect to the serosa. These experiments show that primary culture of rabbit renal cortical cells separated by differential sieves displays electrophysiologic and morphologic characteristics of a proximal renal tubular epithelium. Confluency and attainment of differentiated morphology and function are promoted when monolayer cells are not bound to an unyielding substrate. PMID- 2915992 TI - T-cell receptor V alpha and C alpha alleles associated with multiple and myasthenia gravis. AB - Polymorphic markers in genes encoding that alpha chain of the human T-cell receptor (TcR) have been detected by Southern blot analysis in Pss I digests. Polymorphic bands were observed at 6.3 and 2.0 kilobases (kb) with frequencies of 0.30 and 0.44, respectively, in the general population. Using the polymerase chain reaction (PCR) method, we amplified selected sequences derived from the full-length TcR alpha cDNA probe. These PCR products were used as specific probes to demonstrate that the 6.3-kb polymorphic fragment hybridizes to the variable (V)-region probe and the 2.0-kb fragment hybridizes to the constant (C)-region probe. Segregation of the polymorphic bands was analyzed in family studies. To look for associations between these markers and autoimmune diseases, we have studied the restriction fragment length polymorphism distribution of the Pss I markers in patients with multiple sclerosis, myasthenia gravis, and Graves disease. Significant differences in the frequency of the polymorphic V alpha and C alpha markers were identified between patients and healthy individuals. PMID- 2915994 TI - Peroxidases enhance macrophage-mediated cytotoxicity via induction of tumor necrosis factor. AB - Tumor necrosis factor (TNF) is a monokine which is involved in macrophage mediated cytotoxicity (MMC). We have previously reported that peroxidases can activate thioglycollate-induced macrophages to the tumoricidal state in vitro. The present study was undertaken in an attempt to correlate peroxidase-induced MMC with production of TNF. Horseradish peroxidase (HRP) was used as the principal model for these studies. Resident and thioglycollate-induced macrophages exposed to peroxidases were examined for both MMC against 3T12 cells and production of TNF. Thioglycollate-induced macrophages exposed to HRP, bovine lactoperoxidase, or human myeloperoxidase demonstrated enhanced secretion of TNF. When exposed to HRP, both resident and thioglycollate-induced macrophages secreted significant amounts of TNF and acquired the ability to lyse 3T12 cells. However, resident macrophages were considerably less efficient in both their cytotoxic activity and TNF secretion. Macrophage-mediated cytotoxicity was eliminated by the addition of specific antisera to TNF. In addition, replacement of culture supernatants within 24 hr after exposure of the macrophages to HRP increased tumor cell killing in the absence of additional detectable TNF production, suggesting that other factors may be involved in peroxidase-induced MMC. These results indicate that TNF is intimately associated with peroxidase induced MMC and suggest a possible role for peroxidases as immunomodulators via augmentation of macrophage capacities and functions. PMID- 2915995 TI - Effect of experimental azotemia on intestinal transport of butyric acid. AB - Earlier studies have revealed an impairment of jejunal absorption of long chain fatty acids in experimental uremia. We investigated the intestinal absorption of butyric acid which is a short chain fatty acid in experimental renal failure (RF). Sprague-Dawley rats were randomized into the RF group which had subtotal nephrectomy, a sham-operated control group, and a pair-fed group. In vivo recirculating perfusion (n = 5) and in vitro everted sac incubation (n = 8) were employed. The in vitro experiments were repeated substituting the serosal buffer by either predialysis or postdialysis sera from uremic individuals, or normal serum (n = 10). The rate of in vivo butyric acid absorption was significantly lower while the in vitro absorption was significantly higher in the RF group than those observed in the sham-operated and pair-fed groups which showed comparable values. The normality of butyric acid absorption in the pair-fed animals despite comparable weight loss with the RF group tends to exclude anorexia and weight loss as a cause of altered butyric acid transport in RF animals. The disparity between the in vivo and in vitro data is suggestive of an inhibitory influence of uremic environment which is present in vivo and absent in vitro. This viewpoint was corroborated by the observed fall in butyric acid absorption by sacs containing predialysis uremic serum as compared with those containing normal or postdialysis sera. The latter further suggests that the inhibitory factor(s) is dialyzable. PMID- 2915996 TI - Increased vasodilator responsiveness to BRL 34915 in spontaneously hypertensive versus normotensive rats: contrast with nifedipine. AB - The blood pressure-lowering potency and activity of BRL 34915, a new vasodilator and putative stimulator of potassium efflux from vascular smooth muscle, was investigated in conscious spontaneously hypertensive rats (SHR) and normotensive rats (NTR) after intravenous administration and compared with that of the calcium channel blocker, nifedipine. In SHR, BRL 34915 (3-100 micrograms/kg) or nifedipine (10-3000 micrograms/kg) produced similar reductions in mean arterial pressure of 58 +/- 3% and 55 +/- 3%, respectively. BRL 34915 (ED30% = 13.8 micrograms/kg) was 15.3 times more potent than nifedipine (ED30% = 207 micrograms/kg) in SHR. In contrast, only a 1.7-fold difference in potency was observed in NTR between BRL 34915 (ED30% = 123 micrograms/kg) and nifedipine (ED30% = 182 micrograms/kg). The potency ratio (ED30% NTR/ED30% SHR) for BRL 34915 was 8.83 whereas nifedipine had a ratio of 0.88, reflecting the greater responsiveness of the SHR to BRL 34915. Systemic hemodynamics were monitored in anesthetized SHR and NTR to determine the basis for the reductions in blood pressure. BRL 34915 (3-100 micrograms/kg iv) lowered mean arterial pressure in both groups solely by decreasing total peripheral vascular resistance, since no changes in cardiac output were observed. Relaxation responses were also obtained in phenylephrine-contracted isolated aortic strips from both strains of rat to ascertain whether differences in responsiveness existed at this level of the vasculature. No significant difference in the potency of BRL 34915 (3-10 microM) as a vasodilator was found in aortas from SHR or NTR. These results indicate that, unlike nifedipine, BRL 34915 is a more potent vasodepressor agent in SHR than in NTR and suggests that the potassium efflux stimulator may preferentially relax resistance vessels in the hypertensive rat. PMID- 2915997 TI - Nocturnal increase of type II thyroxine 5'-deiodinase activity in the Syrian hamster harderian gland is abolished by light exposure and induced by isoproterenol. AB - The presence of type II 5'-deiodinase activity in the Syrian hamster Harderian gland was investigated. This enzyme exhibited an increase of its activity after animals entered the normal dark phase, with maximal activity occurring at 04.00 hr (8 hr after lights off). The nocturnal increase was prevented by maintaining the animals in light during the night. Isoproterenol subcutaneously injected every 2 hr (1.0 mg/kg body wt) from 20.00 hr through 0.400 hr to animals exposed to light during the normal dark period mimicked the effect of darkness, i.e., with this treatment an increase in 5'-deiodinase activity with maximal peak values at 02.00 hr was observed. The results show that 5'-deiodinase activity in the Syrian hamster Harderian gland exhibits a nyctohemeral profile dependent on beta-adrenergic activation of the gland. PMID- 2915998 TI - 54Mn absorption and excretion in rats fed soy protein and casein diets. AB - Rats were fed diets containing either soy protein or casein and different levels of manganese, methionine, phytic acid, or arginine for 7 days and then fed test meals labeled with 2 microCi of 54Mn after an overnight fast. Retention of 54Mn in each rat was measured every other day for 21 days using a whole-body counter. Liver manganese was higher (P less than 0.0001) in soy protein-fed rats (8.8 micrograms/g) than in casein-fed rats (5.2 micrograms/g); manganese superoxide dismutase activity also was higher in soy protein-fed rats than in casein-fed rats (P less than 0.01). There was a significant interaction between manganese and protein which affected manganese absorption and biologic half-life of 54Mn. In a second experiment, rats fed soy protein-test meals retained more 54Mn (P less than 0.001) than casein-fed rats. Liver manganese (8.3 micrograms/g) in the soy protein group was also higher than that (5.7 micrograms/g) in the casein group (P less than 0.0001), but manganese superoxide dismutase activity was unaffected by protein. Supplementation with methionine increased 54Mn retention from both soy and casein diets (P less than 0.06); activity of manganese superoxide dismutase increased (P less than 0.05) but liver manganese did not change. The addition of arginine to casein diets had little effect on manganese bioavailability. Phytic acid affected neither manganese absorption nor biologic half-life in two experiments, but it depressed liver manganese in one experiment. These results suggest that neither arginine nor phytic acid was the component in soy protein which made manganese more available from soy protein diets than casein diets. PMID- 2915999 TI - Separation of three commercial forms of vitamin C (ascorbic acid, ascorbic-2 sulfate and ascorbate-2-polyphosphate) by HPLC. AB - A modification of an existing separation technique by this laboratory is described for the separation and quantification of the three commercially available forms of ascorbic acid. The technique has the potential for identifying the various metabolic and degradation products resulting from vitamins C2 and C3 metabolism. A microwave technique is used for tissue heat denaturation and extraction. PMID- 2916000 TI - Barium enema procedure for the pediatric patient. AB - The barium enema examination is considered to be a routine diagnostic study. This article explores this examination and its relationship to the pediatric patient by discussing the history, preparation, and the technical mechanics of the actual examination. PMID- 2916001 TI - Publishing a manuscript: manuscript preparation guide for authors. Part II. AB - Part II presents a guide for manuscript preparation. The guide describes 11 steps necessary to complete a manuscript and is designed to serve several purposes: making the process of having a manuscript published easier for the author and less tedious for the Editorial Review Board; reducing the number of revisions and the revision time; and providing the author with a better chance of getting his or her material published. PMID- 2916002 TI - What radiologic technology educators should know about due process of law. AB - Student rights and the responsibility of educators in providing adequate protection of those rights continues to be a major concern in all educational programs. Due process of law, as it pertains to the schools, outlines specific procedures that should be followed when disciplinary action must be taken involving a student. Applying these guidelines assures fundamental fairness and reasonableness. PMID- 2916003 TI - A "surgical clip" artifact. PMID- 2916004 TI - Peak kilovoltage meter readings. PMID- 2916005 TI - Assessing the need for instructional media support materials. PMID- 2916006 TI - Admissions criteria: eenie, meenie, miney, moe? PMID- 2916007 TI - The professional status of the radiologic technologist. AB - There are regional manpower shortages because of the maldistribution of qualified radiologic technologists. In addition, urban versus rural maldistribution problem exists and is predicted to worsen. This and the identified economic constraints faced by institutions are exerting pressure on the profession to develop programs that will result in multiskilled/multicompetent personnel. Flexibility and receptivity to cross-training opportunities should be studied. In geographic areas where shortages have been identified, it may be necessary for the academic, employing, and health professions to cooperate to develop successful recruitment and retention strategies. Unless corrective action is initiated, there will be a critical manpower shortage in the face of increased demands for radiological services requiring qualified radiologic technologists. It will be necessary for us and the health professions being impacted to individually redefine our mission statements, goals, and objectives to focus on the future, and where common goals exist, to jointly work to achieve these goals. Now is the time for our professional organizations to be pro-active rather than wait to become reactive. We must relinquish protection and act in the best interest of the patient--the number one person in our profession--and in the best interest of the profession. To accomplish this end, radiologic technologists and radiologists must join efforts to improve the professional image of radiologic technologists and the financial benefits. This will help ensure the availability of capable and qualified personnel from today's competitive health occupational arena, and the vast array of other professions that demand bright, articulate students. PMID- 2916008 TI - Limited licensure facts, not fiction. PMID- 2916009 TI - Computers: who needs 'em? PMID- 2916010 TI - Limited licensing: why is the ARRT involved? Part II. AB - Due primarily to economic factors, the concept of the limited scope operator would exist regardless of any organization's position on the wisdom of the concept. Most states that have passed laws as encouraged by federal legislation have been reluctant to legislate people out of existing jobs and have, therefore, incorporated limited categories of practice into their laws. This further assures the survival of the concept of the limited scope of practice. Acknowledging the existence of the position and working to establish reasonable training and competence assessment procedures is in the best interest of the public as well as of the radiography profession. The ARRT is therefore committed to developing examinations for use by states licensing the limited scope of practice operator. The examinations are based upon the philosophy that those persons having a scope of practice that is limited to radiography of the chest or extremities must be as knowledgeable in those particular areas as is the general staff radiographer at entry level as defined by the ARRT Job Analysis Project. Examinations developed using this philosophy will enable states to restrict limited licensing to only those persons having met realistically high standards that are consistent across the country. PMID- 2916011 TI - Dynamic hepatic CT. AB - A technique for incremental dynamic computed tomography (CT) of the liver with boluses of contrast material (with a 50-g iodine load) administered intravenously is described. For most focal liver lesions, which are hypovascular in relation to normal hepatic parenchyma, bolus contrast material enhancement and incremental dynamic scanning improve detectability, compared with that yielded by nondynamic, contrast material infusion techniques. The bolus contrast-enhanced dynamic scan technique is reproducible and of value in patients undergoing sequential CT for assessment of tumor bulk response to chemotherapy. Patients who are potential candidates for resection of focal hepatic lesions should preoperatively undergo intraarterial contrast-enhanced CT. Intravenous bolus enhanced dynamic hepatic CT can be extended to cover more than one anatomic region (eg, abdomen and thorax), as in patients undergoing CT for staging lung carcinoma. In these patients, incremental scan sequences are programmed caudad to cephalad. Incremental dynamic CT is also an appropriate technique to use in cooperative patients who have suffered blunt abdominal trauma. PMID- 2916012 TI - Detection of significant extracranial carotid stenosis with routine cerebral MR imaging. PMID- 2916013 TI - Pulmonary parenchymal disease: evaluation with high-resolution CT. AB - Usefulness of high-resolution computed tomography (HRCT) in locating pulmonary parenchymal disease in relation to the pulmonary lobule was evaluated in 71 patients, including 30 with normal pulmonary parenchyma and 41 with various pulmonary diseases. Both 10-mm-thick sections and 1.5- or 3.0-mm-thick HRCT scans were obtained. Distribution of pulmonary parenchymal disease was classified as centrilobular, panlobular, perilobular, bronchovascular, or nonlobular. Intralobular classification of disease distribution was more feasible in less severely diseased regions. HRCT revealed thickened intralobular bronchovascular bundles in patients with bronchiolitis obliterans, mycoplasma pneumonia, and pulmonary tuberculosis and thickening of both bronchovascular bundles and perilobular structures in patients with sarcoidosis, lymphangitis carcinomatosa, and malignant lymphoma. Centrilobular areas of increased attenuation were seen in patients with bronchopneumonia and pulmonary cryptococcosis. Centrilobular emphysema and bronchiolectasis were recognized only on HRCT images. The improved clarity and sharpness of parenchymal abnormalities on HRCT images, even in severely involved areas, provide additional information about disease distribution. PMID- 2916014 TI - Superior sulcus tumors: CT and MR imaging. AB - Thirty-one patients with superior pulmonary sulcus tumors underwent a total of 32 sets of computed tomographic (CT) and magnetic resonance (MR) imaging examinations before receiving therapy. Prospective, independent, and blinded interpretations of the studies were compared with both the surgical findings (15 patients) and the patient's clinical symptoms (17 patients). Thin-section (5-mm) coronal and sagittal MR images proved more accurate than CT scans (.94 accuracy with MR imaging, .63 with CT) in evaluation of tumor invasion through the superior sulcus. The improved accuracy of MR imaging in this region appears almost certainly to be related to the improved display of the anatomy of the superior sulcus on thin-section coronal and sagittal images. PMID- 2916015 TI - T1N0M0 lung cancer: evaluation with CT. AB - Although computed tomography (CT) is widely used in the evaluation of lung cancer, its use in the evaluation of clinical stage T1N0M0 lung cancer remains controversial. To evaluate the utility of CT, the authors studied 35 patients with clinical stage T1N0M0 lung cancer who underwent CT. Thoracotomy, mediastinoscopy, or fine-needle aspiration biopsy were performed in 26 of the patients. Metastases were proved in six of these patients, with CT demonstrating adenopathy in four of the six and a contralateral mass in one. Chest wall invasion was not demonstrated with CT in one patient. The overall prevalence of metastatic lesions in this group of 26 patients was 23.1%, with 15.4% of the 26 having unresectable lesions. CT demonstrated all metastatic lesions that precluded curative surgery. The results suggest that CT is clinically useful in the evaluation of clinical stage T1N0M0 lung cancer. PMID- 2916016 TI - Anatomy of the minor fissure: evaluation with thin-section CT. AB - The minor fissure was studied with thin computed tomographic (CT) sections in 40 patients. It was absent in eight (20%) and seen in 32 (80%) patients; of these 32 the fissure was complete in seven (22%), incomplete in 23 (72%), and of indeterminate completeness in two (6%). Appearance of the minor fissure on CT scans can be categorized into two major configurations, which are determined by variation in contour of the middle lobe upper surface. The location of the highest point along this surface is either medial (type I configuration) or lateral (type II configuration). The lowest tributary of the vein draining the anterior segment of the upper lobe was seen in 75% of the patients. This vessel was a reliable landmark in delineating boundaries between upper and middle lobes, even when the fissure was radiologically incomplete or absent. In the authors' experience, familiarity with these configurations of the minor fissure has been useful in localization of a lesion in a lobe or determination of its possible extension beyond the fissure into the neighboring lobe. PMID- 2916017 TI - Solitary pulmonary nodules: evaluation with a CT reference phantom. AB - The Zerhouni computed tomographic (CT) reference phantom was used to study 112 solitary pulmonary nodules that were indeterminate with plain tomography. Of the 112 nodules, 33 were more attenuating than the reference phantom and 79 less attenuating. One patient with a previous endometrial malignancy had a pulmonary metastatic lesion that was more attenuating than the reference phantom, presumably due to microscopic calcification. The nodule in the other 32 cases was benign, as determined from follow-up studies of up to 4.5 years or by means of surgical sampling (two patients). Among the 79 nodules that were less attenuating than the reference phantom, 26 were malignant, 22 were benign, and 31 were followed up for up to 4.5 years with no evidence of malignancy. In this series, the CT reference phantom proved to be a useful adjuvant to plain tomography in patients whose nodules were uncalcified and had an indeterminate shape. PMID- 2916018 TI - Peripheral upper lobe collapse in adults. AB - Atypical (peripheral) upper lobe collapse, simulating loculated apical pleural effusion or other localized pleural disease, occurs when the collapsed lobe maintains its adherence to the lateral chest wall. Fifteen such cases are known to have been reported, 12 in children (ten of them infants) and three in adults. Two additional cases, occurring in adults with carcinoma of the bronchus, are presented here. In one case, adherence of the visceral to the parietal pleura was shown to be due to malignant infiltration. In both cases, the margination of the collapsed lobe, which on images resembles apical pleural disease, was attributed to hyperexpansion of the superior segment of the lower lobe. PMID- 2916019 TI - High-altitude pulmonary edema: findings at high-altitude chest radiography and physical examination. AB - Twenty-five male volunteers underwent chest radiography at 550 m above sea level (baseline) and at 4,559 m at 6, 18, and 42 hours after arrival. Nine had a history of high-altitude pulmonary edema (HAPE). Starting by 6 hours and independent of the consecutive presence of HAPE, the diameters of the central pulmonary arteries increased by 10%-30% at 4,559 m. At 18 hours and, increasingly, at 42 hours, radiographic evidence of HAPE developed in eight subjects: six with previously documented HAPE and two without. Radiographic signs of HAPE were most severe peripherally, and morphologic characteristics were compatible with permeability and/or overperfusion edema and normal pulmonary venous pressure. Extensive radiographic findings were accompanied by discrete pulmonary rales, and chest radiography proved valuable in detecting HAPE in subjects with normal findings of lung auscultation. This study demonstrates a significant individual susceptibility of lowland residents with a history of HAPE to develop HAPE, resulting in a recurrence rate of 66%. PMID- 2916020 TI - Adult respiratory distress syndrome from overdose of tricyclic antidepressants. AB - Adult respiratory distress syndrome (ARDS) from overdose of tricyclic antidepressants (TCA) has been reported but is not well known. During a 1-year period, 81 patients with serious overdose from tranquilizers and other psychotropic drugs were examined. TCA alone induced overdose in 30 patients or were combined with other drugs in 26 patients. Twenty-five (31%) patients had overdose from drugs other than TCA. Chest radiography revealed that 30 (54%) patients with TCA overdose and six (24%) patients with non-TCA overdose had abnormalities. Clinical and radiographic findings consistent with ARDS were noted in five (9%) patients with TCA overdose and none of the patients with non-TCA overdose. Five patients with TCA overdose and one (4%) patient with non-TCA overdose had interstitial edema that never progressed to ARDS. TCA should be added to the list of drugs associated with the development of ARDS. PMID- 2916021 TI - MR imaging of the breast: fast imaging sequences with and without Gd-DTPA. Preliminary observations. AB - Of a total of 191 magnetic resonance breast studies performed since March 1984, 82 were performed with gradient-echo fast low-angle shot (FLASH) sequences and fast imaging with steady precession (FISP). These techniques permit imaging of thin and contiguous sections, resulting in high resolution of the parenchymal structure. Intravenous injection of 0.1 mmol/kg of gadolinium diethylenetriamine pentaacetic acid dimeglumine (50% of the dose used in spin-echo sequences) aided in detection of carcinomas as small as 3 mm in dense breast tissue. In 25 patients, dynamic studies were performed at short intervals after the injection of contrast medium in an attempt to differentiate more reliably between breast tissue types. All six malignant tumors found in these 25 patients showed enhancement characterized by a sudden increase in signal intensity on the order of 100% within the first 2 minutes after injection and a much slighter increase thereafter. Sixteen benign lesions showed a substantially different pattern of enhancement. Further studies are required to confirm these findings. PMID- 2916022 TI - Needle localization of nonpalpable breast lesions with a portable dual-grid compression system. Work in progress. AB - A new device and a geometric algorithm facilitate consistent insertion of a needle tip into nonpalpable breast lesions on a single attempt. With the breast compressed by dual grid plates, two oblique exposures are taken. Three intersecting planes through the lesion referenced to the grid markings permit easy determination of the lesion coordinates. In initial trials for preoperative breast lesion localization in 11 patients, the needle tip was within the lesion in nine patients and was within 0.5 cm of the lesion in two patients. The results indicate that this system is very useful for accurate localization and needle aspiration of breast lesions. PMID- 2916023 TI - Association of estrogen receptors with parenchymal pattern at mammography. AB - The authors report on a consecutive series of 1,003 breast cancer cases classified on the basis of Wolfe mammographic parenchymal patterns and estrogen receptor content. The association between these two variables was investigated to assess the reliability of parenchymal patterns in predicting the estrogen receptor status. No significant association was observed after adjustment for possible confounders such as age, menopausal status, and T category. Mammographic parenchymal patterns appear to have no role in predicting estrogen receptor status. PMID- 2916024 TI - Use of Gd-DTPA and fast gradient-echo and spin-echo MR imaging to demonstrate renal function in the rabbit. AB - The paramagnetic magnetic resonance (MR) imaging contrast agent gadolinium diethylenetriaminepentaacetic acid (DTPA) is freely filtered at the glomerulus and is neither secreted nor reabsorbed by the renal tubules. Fast MR imaging techniques, either gradient-echo or spin-echo, can be used to document the passage of Gd-DTPA through the renal tubules, as reflected by alteration in the MR signal intensity within the different anatomic regions of the kidney. Gradient echo (repetition time of 35 msec, echo time of 7 msec, flip angles of 10 degrees 100 degrees) and spin-echo (repetition time of 35 msec, echo time of 8 msec) pulse sequences were used to acquire 20 consecutive images, one every 12 seconds, of the rabbit kidney. Both pulse sequences depicted the time course of Gd-DTPA distribution through the kidney but with distinctly different patterns of MR signal change. These dynamic MR images provide an MR nephrogram that directly demonstrates renal morphology and indirectly reflects the functional status of the renal vasculature, renal perfusion, and tubular concentrating ability. PMID- 2916025 TI - Dynamic Gd-DTPA-enhanced MR imaging of the kidney: experimental results. AB - To determine the normal appearance of dynamic enhanced renal magnetic resonance (MR) images, 25 rabbits were injected with Gd-DTPA and 32 consecutive gradient recalled images were acquired. Several rabbits were also imaged in dehydrated (five animals) and overhydrated (seven animals) states. A reproducible renal enhancement pattern is observed that can be divided into three phases. During the first phase, a peripheral dark band appears, probably representing arrival of Gd DTPA within the arterioles and vasa recta. The second phase begins as a second dark band migrating centripetally toward the medulla; this likely represents the concentration of Gd-DTPA in the descending limb of the loop of Henle. The third phase is characterized by a gradual darkening in the papilla, probably caused by concentration of Gd-DTPA within the collecting ducts. Hydration status influences the duration of these phases. These observations can be explained by the anatomy and physiologic characteristics of the nephron, as well as the MR characteristics of Gd-DTPA at different concentrations. PMID- 2916026 TI - Amyloidosis: diffuse involvement of the retroperitoneum. AB - Systemic amyloidosis diffusely involving the retroperitoneum has not, to the authors' knowledge, been previously reported. The computed tomographic scans of a 68-year-old man showed evidence of diffuse, nonenhancing thickening of the entire retroperitoneum. This appearance mimicked retroperitoneal fibrosis, but the diagnosis of amyloidosis was confirmed at autopsy. PMID- 2916027 TI - Frequency and determinants of adverse reactions induced by high-osmolality contrast media. AB - To determine the frequency of and risk factors for adverse reactions to high osmolality contrast media, the authors prospectively studied hospitalized patients undergoing cardiac catheterization. The authors also studied patients undergoing peripheral angiography and contrast material-enhanced computed tomography (CT) of the head or body who met at least one of the following criteria thought to increase the risk of adverse reactions: age of more than 60 years, diabetes, renal or liver disease, concurrent nephrotoxic drug use, or a history of allergic reactions (n = 795). Criteria were defined and used to group adverse reactions into three classes of clinical severity. Overall, class I (mild), class II (moderate), and class III (severe) reactions occurred in 362 (45%), 44 (5.5%), and three (0.4%) patients, respectively. Class II reactions were relatively common (25%) in patients undergoing cardiac catheterization yet were uncommon (2%) in patients undergoing the other three procedures. Nephrotoxicity occurred in 18 of 651 patients who had follow-up creatinine levels obtained at 48-72 hours. With multivariate regression analysis, the only risk factor (P less than .05) for combined class II and III reactions was diabetes. Diabetes, furosemide use, and a history of atopy (odds ratio = 2.8) were associated with nephrotoxicity (P less than .05). Underlying renal insufficiency was not a risk factor for nephrotoxicity. PMID- 2916028 TI - Natural history of the false channel of type A aortic dissection after surgical repair: CT study. AB - To evaluate the false channel after surgical repair of a type A aortic dissection, postoperative computed tomographic (CT) scans were retrospectively reviewed in 33 patients. Initial CT demonstrated persistence of a double channel distal to the site of surgical repair in 26 patients (79%). In four of these patients serial CT demonstrated enlargement of the false channel, a finding that contributed to the decision to repeat surgery. Progression of thrombus was noted in five patients. Peripheral calcification within the aortic wall of the false channel, presumably located on the "pseudointima," was found in six patients. Because of the progressive nature of type A dissections in the postoperative period, serial CT examinations can provide important information on patients who have undergone surgical correction of a type A dissection. PMID- 2916029 TI - Tantalum vascular stents: in vivo evaluation with MR imaging. AB - Magnetic resonance (MR) imaging at 1.5 T was performed on tantalum vascular stents placed in the aortas of six dogs. The stents produced no significant artifact and allowed for clear depiction of the aortic lumina as flow-void zones with spin-echo imaging and as high-signal areas with gradient-echo imaging. The MR findings correlated with the angiographic studies of the stented vessels. These results demonstrate the feasibility of MR imaging as a noninvasive means of evaluating vessel patency in the presence of tantalum vascular stents. PMID- 2916030 TI - Self-expanding endovascular stent in experimental atherosclerosis. Work in progress. AB - To investigate the physiologic and histologic responses induced by the self expanding endovascular prosthesis, rabbits subjected to a combination of high cholesterol diet and intravascular trauma underwent stent implantation. The results were compared with those obtained with the placement of stents in the healthy aortas of rabbits. Stents in healthy aortic tissue led to stent intimalization, previously reported in canine studies. For stents placed in animals subjected to a high-cholesterol diet but no intimal trauma, it was found that the stent was not the source of atherogenesis. Stents placed in atheromatous plaque were found to radially compress plaque with time and to stimulate for formation of a fibrotic crust. The results suggest that the self-expanding stent protects against progressive encroachment of the vessel lumen by atherosclerotic tissue. PMID- 2916031 TI - Inhomogeneous enhancement of liver parenchyma secondary to passive congestion: contrast-enhanced CT. AB - Passive liver congestion secondary to increased hepatic venous pressure may accompany congestive heart failure. Abnormal patterns of hepatic parenchymal contrast medium enhancement in 25 patients with advanced congestive heart failure who were studied with computed tomography (CT) include a lobulated, patchy, inhomogeneous pattern in all 25 patients, an irregular perivascular enhancement in 14, and a global delay in parenchymal enhancement in nine. CT examinations showed cardiomegaly in the 20 patients with cardiac failure and pericardial effusion or thickening in the five patients with pericardial disease. Also noted were distention of the inferior vena cava (IVC) in 24 patients, hepatomegaly in 23, early reflux of contrast medium into the IVC in 21 and hepatic veins in 16, and hepatic perivascular lymph-edema in six. The abnormal patterns are thought to be due to slowing of hepatic blood flow. Confusion with Budd-Chiari syndrome and other forms of multifocal hepatic disease is avoidable with clinical and radiologic correlation. PMID- 2916032 TI - Hepatic neoplasia: breath-hold MR imaging. AB - Twenty-seven patients with hepatic neoplasms were prospectively examined at 0.35 T with multisection magnetic resonance (MR) imaging during a single breath hold. The procedures included a spin-echo (SE) sequence with a repetition time (TR) of 250 or 125 msec and an echo time (TE) of 15 msec (TR/TE = 250 or 125/15) and gradient-echo (GRE) partial-flip sequences at 250 or 125/20 in phase and 250 or 125/12 out of phase (flip angle of 70 degrees). These procedures were compared with conventional multiacquisition sequences at SE 250/15 (n = 8) in the same patients. GRE partial-flip sequences with a large flip angle provided the optimum combination of contrast and signal-to-noise ratio for imaging hepatic neoplasms, with a signal-difference-to-noise ratio that for in-phase images was 93% greater and for out-of-phase images was 53% greater than that of the SE images. The use of in-phase TEs was preferable to maintain tissue contrast, and presaturation pulses were employed to eliminate vascular pulsation artifacts. All breath-hold procedures provided suppression of motion artifacts superior to that of the short TR, short TE multiacquisition SE imaging. Such sequences should become indispensable for MR imaging of the upper abdomen. PMID- 2916033 TI - Diffuse esophageal spasm: radiographic and manometric correlation. AB - Diffuse esophageal spasm (DES) is characterized by substernal chest pain, dysphagia, and a manometric pattern of frequent simultaneous contractions with intermittently normal peristalsis. The authors correlated the radiographic and manometric findings in 17 patients with DES to better clarify the role of radiography in the evaluation of this uncommon motility disorder. Incomplete or absent primary peristalsis was observed on radiographs in 13 patients (76%), and mild to severe tertiary activity was seen in 12 patients (71%). The mean estimated thickness of the esophageal wall in patients with DES was 2.6 mm compared with 2.5 mm in an age-matched control group of 17 patients with normal esophageal manometric findings (P greater than .05). The authors conclude that most patients with DES show abnormal esophageal motility on radiographs, although the findings were nonspecific and required clinical and manometric correlation. Esophageal wall thickness was normal in patients with DES and appears to be an overemphasized sign in differentiating DES from other esophageal motility disorders. PMID- 2916034 TI - Pseudomembranous colitis with rectosigmoid sparing on barium studies. AB - The classic description of pseudomembranous colitis on barium enema studies is that of pancolitis with thickened haustral folds, a shaggy luminal contour, and/or mucosal plaques. However, the authors describe six patients with proved pseudomembranous colitis in whom barium studies (four double-contrast barium enema studies, one single-contrast barium enema study, and one peroral pneumocolon study) demonstrated rectosigmoid sparing with proximal colitis extending from the cecum to the sigmoid colon (three cases) or to the descending colon (three cases). In all six cases, endoscopy revealed a normal rectum or mild, nonspecific proctosigmoiditis without evidence of pseudomembranes in the rectosigmoid colon. Four patients had an atypical clinical presentation with bloody diarrhea (three cases) or minimal mucous diarrhea (one case). Thus, the diagnosis of pseudomembranous colitis may initially be suggested on barium studies in patients who have relative sparing of the rectosigmoid colon with characteristic findings more proximally in the colon. PMID- 2916035 TI - Transient intussusception in Crohn disease: CT evaluation. PMID- 2916036 TI - Mucinous pancreatic duct ectasia in the body of the pancreas. AB - The authors describe one case of mucinous pancreatic duct cancer (ductectatic cystadenocarcinoma). This disease is characterized by dilatation, with mucoid secretion, in side branches of the main pancreatic duct. Unlike in other reported cases in which mean age of the patients is over 57 years, this case involved a young woman (aged 30 years), and the lesion was located in the body of the pancreas rather than in the uncinate process. Malignant transformation was noted. PMID- 2916037 TI - Appropriate use of bone densitometry. AB - The authors discuss current capabilities of three common bone densitometry techniques--single photon absorptiometry, dual photon absorptiometry, and quantitative computed tomography--and potential capabilities of new innovations of each of these techniques. They believe that use of bone densitometry is valid in the following four clinical applications and recommend its usage to (a) assess patients with metabolic diseases known to affect the skeleton, (b) assess perimenopausal women for initiation of estrogen replacement therapy, (c) establish a diagnosis of osteoporosis or assess its severity in the context of general clinical care, and (d) monitor the efficacy of treatment interventions or the natural course of disease. PMID- 2916038 TI - Occult cartilage and bone injuries of the knee: detection, classification, and assessment with MR imaging. AB - Scant attention has been paid to the role of magnetic resonance (MR) imaging in the assessment of posttraumatic disorders of bone and cartilage at the knee. The authors reviewed 66 cases and identified four types of injuries that were not clearly evident on plain radiographs. A bone bruise was the most common lesion, having a high association with anterior cruciate ligament tears. Osteochondral fractures, stress fractures, and supracondylar femoral and tibial plateau fractures were also identified. MR imaging appears extremely useful in the detection and assessment of bone and cartilage disorders around the knee. PMID- 2916039 TI - Intravertebral fat measurement with quantitative CT in patients with Cushing disease and anorexia nervosa. AB - Dual-energy quantitative computed tomography can be used to calculate the intravertebral fat content as well as to correct the effect of intravertebral fat on bone density measurements. The authors studied seven female patients with Cushing syndrome and 15 female patients with anorexia nervosa--conditions known to result in abnormalities of somatic fat distribution--to determine whether the intravertebral fat content was normal and whether it reflected somatic fat quantities. Intravertebral fat content could not be predicted on the basis of somatic fat, weight, or bone mineral content. Intravertebral fat content was elevated in patients with anorexia nervosa (compared with normal values in young female volunteers). In patients with anorexia, the amount of fat increase was disproportionately large for the severity of osteopenia. In patients with Cushing syndrome, the intravertebral fat content did not differ from that in the volunteers. Intravertebral fat does not correlate well with bone mineral content within any group and appears to be related to other factors. PMID- 2916040 TI - Osteosarcoma: angiographic assessment of response to preoperative chemotherapy. AB - Adjuvant chemotherapy prolongs the survival of patients with high-grade osteosarcoma. Preoperative chemotherapy allows identification of effective agents for adjuvant chemotherapy based on response of the primary tumor. Preoperative determination of tumor response has therapeutic implications, and angiography offers a less subjective means of assessing it than do conventional radiography or computed tomography. Changes in tumor vascularity, as seen angiographically, after two courses and at the time of the last of several courses of preoperative chemotherapy were correlated with histologic tumor necrosis of resected specimens in 81 patients. Angiographically, 40% of the histologic responders and 91% of the nonresponders were identified after two courses of preoperative chemotherapy. After a median of four courses of chemotherapy, 91% of the responders but only 50% of the nonresponders were identified angiographically. Angiographic assessment of tumor vascularity, although not of absolute value, offers a useful guideline for determining the preoperative chemotherapy strategy. PMID- 2916041 TI - Significant extracranial carotid stenosis: detection on routine cerebral MR images. AB - Severe stenosis of the cervical internal carotid artery was detected on magnetic resonance images in three patients from a series of eight with abnormality of flow. In contrast to complete loss of "flow void" in the horizontal carotid within the petrous bone seen in patients with complete occlusion, these three patients had partial flow void in which there was a central area of signal void in the artery, surrounded by circumferential increase in signal in the outer third of the artery. This was seen on axial views at right angles to the long axis of the artery below the petrous bone and on "in-plane" sections through the horizontal carotid canal. An animal model with 70% and 90% carotid stenosis and carotid occlusion was created. The model with 70% stenosis showed no significant change. The 90% stenosis model showed partial flow void in the center of the lumen with peripheral signal exactly as seen in the human patients. PMID- 2916042 TI - Spinal lesions: quantitative and qualitative temporal evolution of gadopentetate dimeglumine enhancement in MR imaging. AB - Seventy gadolinium-enhanced magnetic resonance imaging studies were reviewed, and 36 were selected for quantitative and qualitative analysis of the temporal evolution of contrast medium enhancement of spinal lesions. In the extradural space, lesions often showed mild increase of enhancement on delayed images, but enhancement was always visible on immediate postcontrast images. In the intradural extramedullary space, tumor nodules demonstrated most prominent enhancement on early images, although subtle, strandlike enhancement of the nerve roots showed some delayed uptake of contrast medium on later images. In the intramedullary space, enhancement often increased on delayed images, although this increase was usually mild. For clinical purposes, immediate postcontrast imaging should be sufficient to depict the majority of spinal lesions, regardless of location. However, selected cases, such as necrotic spinal cord tumors, will require delayed imaging. PMID- 2916043 TI - Meningiomas: MR and histopathologic features. AB - The magnetic resonance (MR) appearances of 40 biopsy-proved meningiomas were blindly evaluated and correlated with their predominant histologic pattern- fibroblastic, transitional, syncytial, angioblastic, or mixed. T1-weighted images were not particularly useful in discriminating pathologic subtype, because most tumors were isointense with or hypointense to cortex regardless of histologic type. Signal intensity and features on T2-weighted images strongly correlated with histopathologic findings in over 75% of cases, however. Meningiomas markedly hypointense to cortex on T2-weighted images (seven of 40 cases) were composed predominantly of fibroblastic or transitional elements, while markedly hyperintense meningiomas (14 of 40 cases) demonstrated predominance of syncytial or angioblastic elements. Consideration of secondary features visible at MR imaging (degree of edema, cyst formation, presence of calcium aggregates) led to a more specific histologic prediction in over half of the remaining isointense tumors. The varied MR appearance of meningiomas has a clear histologic basis, and crude prediction of pathologic subtype is possible in over three-fourths of cases. PMID- 2916044 TI - White matter lesions: role of spin density in MR imaging. AB - To study the effect of hydrogen spin density (N[H]) on magnetic resonance (MR) image contrast in white matter disease of the brain, T1, T2, and N[H] values were determined for normal white matter and idiopathic white matter lesions (IWMLs) in 21 patients by using multiple spin-echo (SE) sequences. T1 values of IWMLs were significantly greater than those of normal white matter in all patients studied, and T2 values of IWMLs were significantly greater in 20 of 21 patients. N[H] values of IWMLs were greater in 20 of 21 patients, with statistically significant differences from those of normal white matter in 17 of those 20 patients. Averaged over all 21 patients studied, N[H] values of IWMLs were 20% higher than N[H] values of normal white matter. The effect of unequal N[H] values on contrast between IWMLs and normal tissues is to reduce contrast on short SE sequences with a short repetition time (TR) and a short echo time (TE), while enhancing contrast between IWMLs and normal tissues on long TR/TE SE sequences. Elevated N[H] values in IWMLs have a minimal effect on contrast in conventional inversion-recovery (IR) sequences but substantially enhance contrast between IWMLs and normal brain tissues in short inversion time IR sequences. PMID- 2916045 TI - Cerebral tuberous sclerosis: MR imaging. AB - Nineteen patients with a clinical diagnosis of tuberous sclerosis were examined with high-field-strength magnetic resonance (MR) imaging. Their ages ranged from 6 months to 12 years. In 17 cases, the MR examinations showed both subependymal nodules and multiple peripheral gyral lesions consistent with cortical tubers. Cortical tubers were more frequently demonstrated on spin-echo images obtained with a long repetition time (TR). Because the signal abnormality was located predominantly in the subcortical portion of the tubers, the terms "gyral core" and "sulcal island" were used to describe the patterns noted at MR imaging. Subependymal nodules were best seen on inversion-recovery or short TR spin-echo images, although hypointensity within the nodules consistent with calcification was present in 14 patients and was most evident on long TR spin-echo images. Computed tomographic (CT) scans that had been obtained within 3 years of MR images were available for 13 patients. Intracranial calcification was more accurately diagnosed with CT. However, MR imaging is more sensitive than CT in the detection of gyral tubers and, thus, may be better for screening family members and others in whom tuberous sclerosis is a possibility. PMID- 2916046 TI - Human neoplasm pH and response to radiation therapy: P-31 MR spectroscopy studies in situ. AB - Thirty-five human neoplasms from various sites and of various histologic types and stages were examined with phosphorus-31 magnetic resonance spectroscopy in situ. The tumors included 13 squamous cell carcinomas of the head and neck (lymph nodes), eight Hodgkin lymphomas, six non-Hodgkin lymphomas, four carcinomas of the breast, one melanoma, one sarcoma, one neuroblastoma, and one mucoepidermoid sarcoma of the salivary glands. Thirty-four of the neoplasms had normal to slightly alkaline pH before irradiation. During fractionated radiation therapy, the pH stayed in a range of from near neutral to alkaline and rose to 7.6-8.0 at several time points of radiation therapy for some tumors. These results suggest that most tumor cells in human neoplasms are well oxygenated and that only a negligible fraction are chronic hypoxic cells. The fluctuating alkaline pH during radiation therapy occurred regardless of the responsiveness of the treated tumors. PMID- 2916047 TI - Do radiologists control imaging studies? Survey results from 198 academic institutions. AB - Survey data were collected in 1987 from 198 academic radiology departments in North America to determine the degree to which radiologists are responsible for 32 imaging or imaging-related interventional procedures. The 32 were chosen because they were thought to be potential sources of conflict with nonradiology clinicians. The data reveal that academic radiologists either totally control or strongly dominate bone and breast radiography, percutaneous lung biopsy, percutaneous genitourinary and biliary tract interventional procedures, abscess drainages guided with computed tomography (CT) or ultrasound (US), both peripheral and renal angioplasty, pulmonary angiography, all of neuroradiology, all of CT, and all of magnetic resonance imaging. Radiologists have a dominant role in obstetric US, percutaneous inferior vena cava filter placement, and urethrography, although there is significant participation by nonradiologists in these studies. Radiologists and nonradiologists have roughly equivalent roles in vascular US and hysterosalpingography. Nonradiologists have the dominant roles in percutaneous gastrostomy, endoscopic retrograde cholangiopancreatography, kidney stone lithotripsy, coronary angiography and angioplasty, pediatric angiocardiography, and echocardiography. PMID- 2916048 TI - Brachiocephalic vessels in the elderly: technique for catheterization. AB - Selective catheterization and angiography of brachiocephalic vessels in the elderly may be difficult because of tortuosity and unfolding of the thoracic aorta. Use of a special guide wire contributed to the successful performance of safe femorocerebral angiography with the Simmons sidewinder catheter in the 47 of 48 elderly patients in whom it was performed. All 47 had patent left subclavian arteries. PMID- 2916049 TI - Hydrostatic versus increased permeability pulmonary edema. PMID- 2916050 TI - Bone marrow imaging. PMID- 2916051 TI - Vertebral bone density in children: effect of puberty. PMID- 2916052 TI - Radiologic placement of Hickman catheters. AB - Hickman catheter insertion is usually accomplished surgically by means of either cutdown on the cephalic or jugular veins or percutaneous placement in the operating room. Sixty Hickman catheters were placed percutaneously in an interventional radiology suite in 51 consecutive patients. Complications included one case of pneumothorax and pulmonary artery air embolism (1.7%); one case of brachiocephalic vein thrombosis (1.7%); one case of arterial puncture in a patient with a coagulopathy causing mediastinal hemorrhage, sepsis, and eventual death (1.7%); four cases of catheter sepsis (6.7%); and three cases of suspected local infection or inflammation (5.0%). These rates are comparable to those in surgical series. Radiologic methods increased the convenience, decreased the time and cost of insertion, and enabled superior fluoroscopic control. Modern angiographic materials provide improved safety during access to the subclavian vein. The authors conclude that radiologic Hickman catheter placement offers significant advantages over traditional surgical placement. PMID- 2916053 TI - Chronic arteriovenous fistulas masquerading as arteriovenous malformations: diagnostic considerations and therapeutic implications. AB - Arteriovenous fistulas (AVFs) and arteriovenous malformations (AVMs) may be difficult to differentiate angiographically, and this differentiation has important therapeutic implications. In five cases of chronic AVF, four originally misdiagnosed as AVMs, superselective angiography enabled the correct diagnosis. In two plantar arch fistulas, the technique was further enhanced by manual compression of arterial inflow to decrease the rate of blood flow through the fistula. All five AVFs were successfully occluded. The authors conclude that AVFs and AVMs can be distinguished by means of the appropriate angiographic techniques. PMID- 2916054 TI - Percutaneously placed endovascular grafts for aortic aneurysms: feasibility study. AB - This limited study addressed the feasibility of treating aneurysms with a new transcatheter endoprosthesis. Aortic aneurysms were experimentally created in six dogs and subsequently bridged with nylon-covered, self-expanding metallic stents. The dogs were followed up for as long as 7 months (median, 22 weeks). In each dog, the graft effectively reconstituted the aortic lumen, excluding the aneurysm. One dog exhibited minimal (less than 1-mm) residual dilatation at the site of the aneurysm 7 months after graft placement. The nylon material acted as a support and template for neointimal encasement, enabling the formation of a new vascular lumen. It also remained porous at the origin of aortic side branches, preserving the visceral blood supply. One of the endovascular grafts failed to expand completely at its distal end, which promoted thrombus formation within the graft and resulted in the occlusion of both renal arteries. The dog was found comatose 48 hours after graft placement and was killed at that time. PMID- 2916055 TI - Percutaneous transrenal endoureteral radio-frequency electrocautery for occlusion: case report. AB - In a patient with advanced cervical carcinoma who had a large vesicovaginal fistula, the authors applied radio-frequency (RF) current endoluminally to the ureter via a percutaneous nephrostomy tract to occlude the ureter. Perineal drainage was initially reduced and then stopped entirely. The procedure was relatively easy to perform and was successful in achieving occlusion until the patient's death 2 1/2 months later. PMID- 2916056 TI - Role of interventional radiology in the management of major esophageal leaks. AB - Six patients with major esophageal leaks associated with pleural and mediastinal abscesses were treated by means of fluoroscopically placed drainage tubes. In each patient, large-bore sumps were positioned in the esophagus to obtain optimal diversion of enteric contents. Mediastinal and pleural collections were drained percutaneously or with catheters passed through the esophagus and across the esophageal rent. Closure of the esophageal disruption without further surgery was achieved in all patients. PMID- 2916058 TI - Hepatic artery model for evaluating the distribution of intraarterial chemotherapy infusion: nonpulsed versus pulsed infusions. AB - The effect of a commercially available pulsatile slow-infusion system on the degree of infusate mixing and distribution was assessed in a life-size glass model of the hepatic arterial system. The authors determined, both visually and quantitatively, the mixing homogeneity of a low-flow infusion (1.4 mL/min) of red dye through a side-hole catheter (2.5 F outer diameter) into pulsatile flow (300 mL/min) of a fluid with the same viscosity as blood. When comparing nonpulsed versus pulsed infusion techniques, the authors found that the pulsatile infusion system did not significantly improve the inhomogeneity of dye distribution in the 16 hepatic arterial branches. The results of this in vitro study suggest that a pulsatile infusion system that uses low pulse velocities without regard for cardiac cycle is less than optimal and does not significantly improve drug mixing at the standard slow infusion rates. Moreover, as potential new intraarterial delivery systems are developed to improve drug mixing, in vitro models may be the most useful means of initially evaluating their efficacy. PMID- 2916057 TI - Symptomatic vascular malformations: ethanol embolotherapy. AB - Absolute ethanol was used to perform nine transcatheter embolizations and 21 direct percutaneous puncture embolizations in eight patients with unresectable vascular malformations. Six patients had arteriovenous malformations and two patients had hemangiomas. Four of these patients had undergone unsuccessful surgery, and the other four were not considered candidates for operation. All large complex symptomatic vascular malformations (SVMs) required multiple embolizations that were staged procedures. Ethanol embolotherapy, performed according to strict techniques, has proved efficacious in the management of SVMs. PMID- 2916059 TI - A 4-F coaxial catheter system for pediatric vascular occlusion with detachable balloons. AB - Detachable latex balloons, preloaded coaxially in 4-F angiographic catheters, were used in eight patients, aged 6 weeks to 12 years. Successful placement of the balloon was achieved in six patients, in whom the feeding arteries arose in an oblique fashion from the aorta or main conducting arteries. Placement was not possible in two patients. No femoral or axillary arterial occlusions occurred as a result of these procedures. The balloon can be inflated up to 8 mm in diameter, passes readily through a 4-F introducer sheath, and can be retrieved, without detachment from the catheter, through the same sheath. A hemostatic side-arm adapter attached to the catheter permits angiography to be performed before balloon detachment. The disadvantages of the system include preparation time to hand tie the balloons, the operator experience required, and difficulty in navigating the balloon. PMID- 2916060 TI - Political trends in vascular and interventional radiology: a randomized survey. AB - There is a trend in the United States toward the performance of vascular and interventional radiology procedures by nonradiologists. A survey was conducted of 2.069 U.S. radiologists to define better the current status of and gather opinions on the future of vascular and interventional radiology. A total of 715 (35%) completed questionnaires were returned. Cross tabulations among subgroups of respondents were performed to address key issues. The median proportion of time spent in the performance of vascular and interventional radiology was 10%, and 51.5% of the radiologists surveyed were in groups that included a fellowship trained interventional radiologist. More than half (54.4%) of the radiologists indicated that nonradiologists have expressed interest in performing vascular and interventional techniques. According to 13.4% of the radiologists surveyed, cardiologists performed at least some peripheral angiography or angioplasty. The vast majority of radiologists (96.8%) did not want other specialties to assume vascular and interventional radiology procedures, but 16.8% believed these procedures will eventually be lost to other specialties. The results indicate that vascular and interventional radiology is being infringed on to a relatively large degree by other specialties. PMID- 2916061 TI - New interventional devices and the need for restraint. PMID- 2916062 TI - Role of the department chairman in the future of interventional radiology. PMID- 2916063 TI - Developing an interventional radiology practice in a community hospital: the interventional radiologist as an equal partner in patient care. AB - Development of an interventional radiology practice or section depends first on the commitment and ability of the interventionalist but is also contingent on an appropriate environment. Moreover, the interventionalist must attempt to change long-standing concepts and referral patterns with aggressive dissemination of information. He or she must be an advocate of the procedures offered, as well as their benefits to the patient and the health care system. One must actively include outpatient visits and admissions as part of services offered. Allies in this effort include primary care physicians, internists, hospital administration, and third-party payers. In addition, organized radiology can now offer some assistance through the Society of Cardiovascular and Interventional Radiology and the American College of Radiology. All of these factors will contribute significantly to the success of interventional radiology in both teaching and community hospital settings. PMID- 2916064 TI - Cardiovascular and interventional radiology fellowship training programs. PMID- 2916065 TI - Evaluation of polymer-coated balloon-expandable stents in bile ducts. AB - The long-term patency of and biologic response to the presence of polymer-coated balloon-expandable intraluminal stents in the bile ducts was studied in 18 dogs. Metallic stents coated with two different polymers (silicone rubber and segmented polyether-polyurethane) were placed in 12 dogs and uncoated stents in six, and animals were killed after 4, 12, and 24 weeks of observation. Cholangiograms were obtained at 1, 4, 6, 12, and 24 weeks, depending on length of follow-up. All bile duct segments containing stents remained patent throughout the follow-up periods. Characteristic luminal narrowings due to hyperplastic papillary mucosa occurred with all three stent types. although no difference could be found in the degree of narrowing of the most restrictive segment among the three stent types, mucosal proliferation was most extensive with the uncoated stent. Lack of concretion buildup and benign tissue response encourage the development of a clinically useful expandable biliary endoprosthesis. PMID- 2916066 TI - Self-expanding stainless steel biliary stents. AB - Self-expanding stainless steel stents of a modified Gianturco design were used to relieve biliary obstruction in 31 patients. Fifteen patients had benign strictures, and 16 patients had malignant obstructions. The median age was 62 years. The stents were placed through a 10-F sheath, and in most cases multiple stents were used. Complex malignant obstructions involving multiple systems were successfully treated with stainless steel stents in order to reconstruct the biliary tree. Stents have been in place for more than 6 months in 20 of the 31 patients; occlusions have occurred in 10% of the 31 patients. Patients with benign postoperative strictures have done very well, with one patient free of symptoms at 14 months. The initial results are encouraging. Further studies will determine the role of stainless steel stents in the treatment patients with benign postoperative strictures and malignant obstructions with involvement of multiple systems. PMID- 2916067 TI - Experimental percutaneous gallstone lithotripsy: results in swine. AB - The Kensey-Nash device is used to fragment gallstones percutaneously. It is inserted into the gallbladder through an 8-F introducer sheath, a cage is expanded to protect the gallbladder, and the impeller is activated. A strong vortex automatically pulls the stones into the basket. The device was tested in 24 pigs in which human gallstones (5-19 mm, bilirubin and cholesterol types) had been implanted and in two control pigs with no gallstones. All pigs except two were killed immediately after the procedure (acute studies); the two were followed up for 36 days and then killed. Fragments (1-3 mm) were similar in size to those seen in current extracorporeal shock wave lithotripsy studies. A complication occurred in one animal, and technical failures occurred in two, causing these three studies to be aborted. PMID- 2916068 TI - Role of percutaneous intracorporeal electrohydraulic lithotripsy in the treatment of biliary tract calculi. Work in progress. AB - Although surgery is the treatment of choice for symptomatic gallstones, most bile duct calculi can be successfully treated with the use of routine percutaneous or endoscopic methods. Failure of these methods is most often associated with stones larger than 1.5 cm. The authors used percutaneous intracorporeal electrohydraulic lithotripsy (EHL) to treat 11 patients with calculi in the bile ducts (n = 10) or gallbladder (n = 1) in whom the use of other percutaneous or endoscopic methods failed. The stones in all 11 patients were successfully fragmented and removed. There were no complications. Intracorporeal EHL is an effective alternative therapy for the treatment of biliary tract calculi when standard methods fail. PMID- 2916069 TI - Multidisciplinary approach to complex endoscopic biliary intervention. AB - Endoscopy is frequently used to treat biliary abnormalities; however, controlling the catheter is difficult when tortuous structures or specific intrahepatic ducts must be negotiated. Intraductal manipulation with conventional angiographic guidance is difficult, and combined transhepatic approaches are painful, associated with risk, and cumbersome. The authors describe a multidisciplinary approach to complex endoscopic procedures in which the interventional radiologist controls catheter and guide wire placement. Of 344 procedures attempted over a 3 year period, 304 were accomplished with transendoscopic- or fluoroscopic-guided methods alone. Combined transhepatic procedures were performed in the other 40 cases. The success rate of endoscopic procedures and the number of conditions treatable with nonoperative interventional methods are increased with a multidisciplinary approach. PMID- 2916070 TI - Biliary duct stones: update on 54 cases after percutaneous transhepatic removal. AB - Percutaneous transhepatic removal of common bile duct stones was performed 54 times in 50 patients with a success rate of 93%. In all patients, a modified Dormia basket was inserted through a percutaneous transhepatic catheter, and the stones or fragments were advanced into the duodenum. All patients had contraindications to surgery or had undergone unsuccessful attempts at endoscopic retrograde cholangiopancreatography and sphincterotomy. Monooctanoin (25 patients) or methyl tertiary-butyl ether (four patients) was infused to reduce stone size or remove residual debris. The average time for complete stone removal was 8.6 days. Morbidity was 13% and mortality was 4%, results which compare favorably with those of surgery. PMID- 2916071 TI - [Antisemitism in psychoanalyses. On the identity of Austrian psychoanalysts today]. AB - Jews living in present day Austria represent "uncanny"--repressed and dangerous- instinctual wishes as well as reminders of the mass murder in which the previous generation of non-Jews was implicated. This results in an intensification, rather than an abatement, of antisemitic prejudice. Non-Jewish analysts partake of this dynamic as well. PMID- 2916072 TI - ["The Jews interpret in a crazy manner." Evaluation of a classical text]. AB - The author scrutinizes a text taken from the law of Justinian, 553 A. D., which assigns the Jews a place in the occidental-Christian system of thought. The identity of personal power, whether imperial or papal, and legal text merges the real and the symbolic. That is, authority determines the interpretation of the text. The author designates this the Christian-industrial religion and the Christian-industrial psychology and thereby draws connections with the present. Jewish textual interpretation, in which the text alone yields authority, is nourished--like psychoanalysis--by the tension between reality and fantasy, by the contradiction between power and desire. PMID- 2916073 TI - [Genetic origins of the controversy between Freud and Romain Rolland on religious feelings]. AB - The author conceptualizes Freud's views of faith and religious feeling against the background of his friendship with Romain Rolland. Among the contributing biographical factors are Freud's confrontation with death--his own and that of his brother Julius--and his relationship with his mother. PMID- 2916074 TI - [A case of phallic-narcissistic personality]. PMID- 2916075 TI - The fibromyalgia syndrome. PMID- 2916076 TI - Neurohormonal aspects of fibromyalgia syndrome. AB - There is a growing awareness that fibrositis/fibromyalgia syndrome is a systemic disorder for which a pathogenic mechanism must be sought. A generalized deficiency of the neurotransmitter, serotonin could explain many of fibromyalgia's typical manifestations. The serotonin deficiency hypothesis is appealing because it provides a number of experimental approaches that can now be used to further study the pathogenesis of this disorder. PMID- 2916077 TI - Aluminum removal after chronic intoxication in rats. AB - Aluminum concentrations were measured in serum and in the bone, liver, spleen, kidney and brain of male Wistar rats treated with aluminum lactate. The administration was performed intraperitoneally over a period of 109 days, giving a total elemental aluminum dose of 128 mg per rat. After loading, a group of animals was killed together with blanks to verify the level of aluminum accumulation. Two groups of remaining rats were administered with deferoxamine over a period of six and fifteen weeks, respectively, receiving total doses of 270 and 675 mg of DFO. The concentrations of aluminum in serum and in tissues were compared with those found in other groups of animals undergoing aluminum suspension. The determination of iron in liver was also performed. Results indicate that in this experimental model the action of deferoxamine was preferential toward tone while it seemed lacking in the other examined tissues. PMID- 2916078 TI - Effects of adjuvant arthritis on copper, zinc, and iron metabolism in the rat. AB - In a study on the effects of adjuvant arthritis on copper (Cu), zinc (Zn), and iron (Fe) metabolism in the rat, most significant changes were observed in the liver and pancreas where arthritis caused a large increase in the concentrations of all three metals. Results also indicated that although arthritis-induced changes in metal concentrations were highly correlated to inflammation and occurred in selected tissues only, these changes were not selective for copper. PMID- 2916079 TI - Effect of PAF on selected smooth muscle preparations. AB - The myotropic activity of PAF (Platelet activating factor) was studied on selected smooth muscle preparations from the rat and the guinea-pig, and compared with the responses to histamine, acetylcholine, norepinephrine, leukotriene D4 (LTD4), prostaglandin (PG) E2 and F2 alpha. Our results showed that nanogram quantities of PAF induced strong contractile responses. Tachyphylaxis appeared as a common feature of PAF activity. The responses were usually slow in onset and sustained. Leukotriene D4 and prostaglandin E2 also contracted most tissues used except the lung tissues where prostaglandin E2 induced a relaxation. PMID- 2916080 TI - Diltiazem (0.5 mg/l) decreases coronary vascular resistance during reperfusion, but not during low flow ischemia, in the isolated perfused rat heart. AB - Isolated rat hearts underwent low flow perfusion with a perfusion pressure of 15 mmHg for two hours followed by reperfusion at a perfusion pressure of 80 mmHg for two hours. In these severely damaged hearts we tested whether diltiazem (0.5 mg/l) administered during ischemia or during reperfusion had vasodilatory effects. Ischemia-induced progressive vasoconstriction was not influenced by the presence of diltiazem: during ischemia coronary vascular resistance (CVR) rose from 3.3 +/- 0.1 to 46.4 +/- 17.6 mmHg.ml-1.min in the diltiazem group and from 3.5 +/- 0.1 to 42.4 +/- 5.3 mmHg.ml-1.min in the control group (n.s.). If diltiazem was administered during reperfusion only CVR dropped from 45.7 +/- 9.2 to 4.4 +/- 1.1 mmHg.ml-1.min in the presence of diltiazem, and from 47.1 +/- 11.6 to 9.3 +/- 1.5 mmHg.ml-1.min in the control group (P less than 0.025). The disparity between diltiazem's effects during ischemia and reperfusion suggests a different mechanism of Ca2+-influx in vascular smooth muscle cells in ischemic and reperfused hearts: in reperfusion through the Ca2+-channels which are sensitive to calcium antagonists, and in ischemia through other channels, like the Na+/Ca2+ exchanger, or from intracellular calcium stores. PMID- 2916081 TI - Adverse effects of the antifertility agent DL 717-IT (Canocenta, Byk Gulden, FRG). Pathological findings in the rabbit. AB - The post-coital antifertility agent DL 717-IT (Canocenta, Byk Gulden, FRG) was administered to sixteen female (5 pregnant and 11 nonpregnant) New Zealand White (NZW) rabbits by single i.m. injections at a dose of 2.5 mg/kg body weight. The corresponding number of controls received the vehicle of the drug only. Pregnancy was interrupted in all the DL 717-IT-treated rabbits. Obvious loss of bodyweight (-15% at mean) was observed in all the test animals during the first two test weeks after treatment. Same sized groups of test and control animals were euthanasized 3, 4, 5, and 6 weeks after the initiation of the treatment and complete necropsies and histological examinations were performed. One of the test animals died on day 21. Pathological findings involved epidermal hyperplasia, hyper- and dyskeratosis seen in 16/16, zonal and massive liver necrosis in 8/16, generalized degeneration of the skeletal muscles in 6/16, and focal myocardial necrosis in 5/16 test animals. Vitamin A concentrations in liver tissue were found to be significantly reduced in the experimental animals compared to the controls. Consequently the skin lesions may possibly be explained as the result of reduced vitamin A synthesis due to DL 717-IT-induced hepatocellular damage. The results of this study indicate severe toxic effects of DL 717-IT in the given formulation in the rabbit at dosages reported to be well tolerated in several species and recommended for veterinary use to terminate unwanted pregnancies in the bitch. PMID- 2916082 TI - Metabolic activation and covalent binding to nucleic acids of pentachloroethane as short-term test of genotoxicity. AB - The in vivo covalent binding of 14C-pentachloroethane to DNA, RNA and proteins of rats and mouse organs was detected 22 hr after i.p. injection. The covalent binding index, calculated on the liver labeling was comparable to those of compounds considered as weak-moderate initiators. Like other haloalkanes, 14C pentachloroethane was bioactivated in in vitro cell-free system by both microsomal and cytosolic enzymatic fractions from mouse and rat organs to react covalently with DNA and other macromolecules. The binding extents obtained from in vitro incubation and the binding values detected after in vivo administration of labeled pentachloroethane were comparable each other and showed a high correlation with oncogenic potency index of this compound. This result confirms the efficiency of in vitro binding as short-term test of genotoxicity prediction. PMID- 2916083 TI - Reduced DNA repair response of carcinogen-induced hyperplastic cells in rat urinary bladder exposed to N-methyl-N'-nitro-N-nitrosoguanidine in organ culture. AB - DNA repair response to N-methyl-N'-nitro-N-nitrosoguadine (MNNG) was examined in an organ culture of hyperplastic urinary bladder epithelium, induced by N-butyl-N (4-hydroxybutyl)nitrosamine (BBN) in male F344 rats. Organ cultures of urinary bladders obtained from rats given a solution of 0.05% BBN for 4-12 weeks, were processed and exposed to MNNG (10(-3)M). The DNA repair response was estimated by autoradiographic analysis of unscheduled DNA synthesis (UDS). In general, hyperplastic cells of the urinary bladder induced by BBN showed lower UDS levels than those of non-hyperplastic cells. The reduction of DNA repair response to MNNG was more prominent in advanced hyperplastic cells with longer BBN treatment than in early appearing hyperplastic cells with shorter BBN treatment. PMID- 2916084 TI - [Indications for surgery in the treatment of cancer of the uterine neck]. PMID- 2916085 TI - [Therapeutic options in invasive cancer of the uterine neck]. PMID- 2916086 TI - [A years' treatment of Paget's disease of bone using salmon calcitonin via nasal spray]. PMID- 2916087 TI - [Import of tropical human cutaneous myiases]. PMID- 2916088 TI - [A rare case]. PMID- 2916089 TI - [A pulsating swelling in the neck]. AB - This 56-year-old male patient came to our emergency ward because of a painless pulsation on his left neck. The clinical examination revealed an irregular pulse and a systolic murmur praecordially. In further diagnostic procedures the diagnosis of a severe tricuspidal insufficiency could be confirmed. In the history of the patient there was a motorcycle accident with blunt chest trauma which had to be considered as cause of the lesion. PMID- 2916090 TI - [A case from practice (126). Patient: E.W., born 4-16-1936]. PMID- 2916091 TI - [Rare variants and unusual course of Cushing's syndrome]. AB - Cushing's syndrome is a rarely observed disease with a poor prognosis when not treated appropriately. Knowledge of clinical features of the different forms of the disease together with a specific and subtle method of cortisol detection is indispensable for an early out-patient diagnostic program. In this study the characteristic features of the rare benign and malignant forms of Cushing's syndrome are presented in typical case-reports. As it has been proven in clinical experience, the necessary diagnostic measures for clarification of the syndrome consists of only few methods reliable concerning their diagnostic validity. The success of any curative treatment of the benign forms or any palliative measure of the malignant forms essentially depends on early diagnosis and differentiation of the various appearances of Cushing's disease. PMID- 2916092 TI - Salmonella typhi infections in the United States, 1975-1984: increasing role of foreign travel. AB - To explore changes in the epidemiology of typhoid fever in the United States, cases reported to the Morbidity and Mortality Weekly Report (MMWR) and typhoid case report forms submitted by state and local governments are reviewed. The incidence of typhoid fever in the United States fell from one case per 100,000 population in 1955 to 0.2 cases per 100,000 in 1966 and has since remained fairly stable. Review of case report forms for 2,666 cases of acute typhoid fever that occurred between 1975 and 1984 showed that 62% were imported, in contrast to only 33% during 1967-1972. The proportion of cases imported has continued to rise, reaching 69% in 1984. The major sources of the 1975-1984 cases were Mexico (39%) and India (14%). The case-fatality rate was 1.3%. Antimicrobial resistance was a minor problem, and large outbreaks were unusual. Further decline in the incidence of typhoid fever in the United States probably must await the advent of an effective vaccine with minimal adverse effects for use by travelers. PMID- 2916093 TI - Infections associated with animal exposure in two infants. PMID- 2916094 TI - SI units and the clinical practice of infectious diseases: application to the usage of antimicrobial agents. AB - Over the next few years, le Systeme international d'Unites or SI units may replace the presently used metric system in reporting laboratory data. The change to SI units will likely result in some confusion among clinicians who are not well versed in the new system. Application of SI units to the clinical practice of infectious diseases is discussed, including changes in drug dosages, serum drug levels, and minimum inhibitory concentrations. A table is presented to facilitate conversion of metric units to SI units and vice versa. PMID- 2916095 TI - Opportunistic infections in "normal hosts". PMID- 2916096 TI - Enterococcal bacteremia: analysis of 75 episodes. AB - Seventy-five cases of enterococcal bacteremia were analyzed retrospectively. Most patients had serious underlying disease and blood cultures became positive on an average of 27 days after admission. Polymicrobial bacteremia occurred in one third of the patients. Twenty-two (30%) of the patients died during hospitalization; nine of these deaths were directly due to enterococcal bacteremia. Metastatic infections occurred in seven patients, including five with endocarditis. More than 40% of the patients were receiving antibiotic therapy at the time of bacteremia; cephalosporins were being administered to 56% of these. Thirty-eight patients were treated with two antibiotics. The commonest regimen was ampicillin and gentamicin; 90% of these patients responded. Eighteen patients were treated with only one antibiotic; 89% of these patients responded. Nineteen patients received no antibiotic therapy; the majority of these patients responded despite lack of therapy. Two-drug regimens are not always required for the treatment of enterococcal bacteremia, and treatment must be tailored to the particular clinical situation. PMID- 2916097 TI - Neonatal meningitis due to Streptococcus mitis. AB - A baby girl became ill 2 days after a normal delivery. Streptococcus mitis was isolated from the cerebrospinal fluid, and she recovered uneventfully on treatment with penicillin and, for the first 2 days, netilmicin. The organism was penicillin-tolerant in vitro. Non-groupable alpha-hemolytic streptococci are an uncommon cause of meningitis; three cases have been ascribed to S. mitis. PMID- 2916098 TI - Periprosthetic candidal infections following arthroplasty. AB - Candidal infection after prosthetic arthroplasty has been reported in six previous cases, to which four cases are now added. Candida albicans was the offending organism in four patients, Candida parapsilosis in three, Candida tropicalis in two, and Candida (Torulopsis) glabrata in one. None of the 10 patients had evidence of disseminated candidiasis, and, except for the uniform presence of a prosthesis, other underlying factors that are generally associated with candidal infections were present in only three. Clinical features that distinguished periprosthetic from natural bone and joint infection included an older patient population, the usual lack of predisposing factors other than the prosthesis, and the absence of evidence of disseminated candidiasis. All patients were treated with removal of the prosthesis and antifungal therapy, consisting of amphotericin B alone (six patients) or combined with 5-fluorocytosine (three patients) or ketoconazole (one patient). Infection appeared to be cured in nine of the 10 patients, but the follow-up was less than 1 year in five cases. Replacement with a new prosthetic joint was attempted in only two cases and successful in only one. Direct inoculation of organisms during surgery or transient unrecognized candidemia may initiate periprosthetic infection, which might then be promoted by favorable local factors, both mechanical and molecular. The role of prosthetic materials, candidal adhesins, and human factors such as fibronectin in initiating these infections has yet to be characterized. PMID- 2916099 TI - Infectious complications of craniofacial surgery in children. AB - During the 10-year period 1975 through 1984, 219 children with congenital anomalies underwent oromaxillary or craniofacial surgery at Children's Medical Center, Dallas. There were no infectious complications following 56 oromaxillary procedures. The overall rate of infection following craniofacial surgery was 14.7% (24 of 163). Infection rates were significantly increased when a combined (monoblock) repair was performed (45% [15 of 33]), compared with either intracranial (8% [six of 72]) or extracranial (5% [three of 58]) procedures alone (P less than .001). The variables identified by multivariate discriminant analysis as useful independent predictors of postoperative infection were, in order of decreasing importance: length of operation, type of procedure (intracranial, extracranial, or combined), and age. Staged procedures are recommended for craniofacial surgery whenever possible because of the significant increase in rate of infection associated with the monoblock repair. PMID- 2916101 TI - [Nursing administration in the hospital. What is administration of nursing?]. PMID- 2916100 TI - Pseudomonas putrefaciens bacteremia. AB - Pseudomonas putrefaciens is an unusual cause of human disease. Since 1978 only five cases of bacteremia due to this organism have been reported. Within 12 recent months four cases of bacteremia due to P. putrefaciens were seen - two occurred in patients with chronic infections of a lower extremity, one in a patient with neutropenia, and one in a patient with fulminant septicemia and disseminated intravascular coagulation. Two of the patients had prostheses; in neither case did prosthetic infection or prosthetic failure occur. Two syndromes of bacteremic infection with P. putrefaciens are suggested. One syndrome is associated with chronic infection of a lower extremity, is fairly well tolerated, and responds to appropriate antimicrobial agents. The other syndrome is more fulminant and may be associated with severe underlying debility, liver disease, and malignancy. It is not yet known whether this is a meaningful distinction. The significance of the recent increase is the isolation of this organism is not clear at present. PMID- 2916102 TI - [Nursing consultation in mental health]. PMID- 2916103 TI - [Parenteral administration of anti-infective agents. What do nurses know?]. PMID- 2916104 TI - [Home nursing and primary health care]. PMID- 2916105 TI - [Education in alimentation, nutrition and dietetics]. PMID- 2916106 TI - [Continuous ambulatory peritoneal dialysis. 2. Accessory materials for CAPD]. PMID- 2916107 TI - [Continuing education. 33. Field: basic nursing. Topic: fundamentals of nursing]. PMID- 2916109 TI - [Decrease in systemic fungal infections in hematological neoplasms with empirical use of amphotericin B therapy]. AB - An incidence of up to 30% of systemic fungal infections at autopsy, and difficulties in diagnosing systemic mycosis antemortem, have led to the empiric use of amphotericin B in patients with hematological malignancies. Routine empiric anti-fungal treatment was initiated at our institution in 1982. Amphotericin B and initially for 3 days flucytosine was given to granulocytopenic patients with unremitting (after 48-72 h) or recurrent fever during antibiotic treatment, or with newly detected pulmonary infiltrates, sinusitis, and skin and retinal lesions suggestive of fungal infection. With this approach the rate of systemic fungal infections decreased from 10% to 4% (p less than 0.02). The reduction was most prominent in patients with acute myelogenous leukemia, where fungal infections decreased from 16% to 4% (p less than 0.025). PMID- 2916110 TI - The Natural Death Act (Living Will)--a poor solution to a problem that does not exist. PMID- 2916108 TI - [Positive direct Coombs' test in acute leukemias and other hemoblastoses: relation to clavulanic acid-containing antibiotics?]. AB - Alerted by a high incidence of positive autologous controls in pretransfusion compatibility testing for patients with acute leukemia, we retrospectively analysed 59 cases of severe hemoblastoses undergoing myelosuppressive treatment. Seventeen (29%) of these patients had a positive direct antiglobulin test (DAT) with the following characteristics: the test was of the IgG and/or C3d type in all but two cases, which reacted with polyvalent antiglobulin sera only; the reaction was very weak throughout; very high concentrations of monospecific sera were needed to elicit positive reactions; free antibodies were never detected in the patients' serum; the eluates of the patients' red cells were non-reactive against a very large panel of test erythrocytes. All these criteria suggested a non-immunologic absorption of proteins under the influence of drugs such as cephalosporins and clavulanic acid. Timenten (ticarcillin and clavulanic acid) was found to be the only common drug which had been administered to the majority of the patients with a positive DAT: 15 of the 17 patients with a positive DAT (88%) had received Timenten against 19 of 42 patients (45%) with negative DAT. 44% of all the patients receiving Timenten thus had a positive DAT, whereas only 8% of the patients without this drug reacted in this way. These data document the role of clavulanic acid in the development of a positive DAT. The literature and our experience show that this kind of unspecific binding of proteins to the red cell membrane is not associated with increased hemolysis. Knowledge of the phenomenon, however, is important for differential diagnosis of anemias and interpretation of difficulties arising during pretransfusional compatibility testing. PMID- 2916111 TI - Unresolved complaints can lead to malpractice litigation. PMID- 2916113 TI - Animals in research: educational funds. PMID- 2916112 TI - Blank check laws. PMID- 2916114 TI - A clash of cultures at meeting on misconduct. PMID- 2916115 TI - Genome project gets rough ride in Europe. PMID- 2916116 TI - Biotechnology rules wither in OMB. PMID- 2916117 TI - Is it healthy to be chaotic? PMID- 2916118 TI - Molecular dynamics simulation of a phospholipid micelle. AB - The dynamic character of phospholipid aggregates limits conventional structural studies to the determination of average molecular features. In order to develop more detailed descriptions of phospholipid structure for comparison with experiment, the molecular dynamics of a hydrated lysophosphatidylethanolamine (LPE) micelle, incorporating 85 LPE and 1591 water molecules, have been simulated. Comparison of the initial and equilibrated micelles shows substantial differences both in LPE hydrocarbon chain conformation and polar head-group solvent interactions. Although these changes produce only subtle effects on the averaged structural properties of the system, the alterations in hydrocarbon chain packing and head-group solvation appear to mimic a polymorphic pretransition from a spherical toward a cylindrical micelle structure. PMID- 2916119 TI - Muscarinic modulation of cardiac rate at low acetylcholine concentrations. AB - Slowing of cardiac pacemaking induced by cholinergic input is thought to arise from the opening of potassium channels caused by muscarinic receptor stimulation. In mammalian sinoatrial node cells, however, muscarinic stimulation also inhibits the hyperpolarization-activated current (If), which is involved in the generation of pacemaker activity and its acceleration by catecholamines. Acetylcholine at nanomolar concentrations inhibits If and slows spontaneous rate, whereas 20 times higher concentrations are required to activate the acetylcholine-dependent potassium current (IK,ACh). Thus, modulation of If, rather than IK,ACh, is the mechanism underlying the muscarinic control of cardiac pacing at low (nanomolar) acetylcholine concentrations. PMID- 2916120 TI - Koop finds abortion evidence "inconclusive". PMID- 2916121 TI - AIDS paper raises red flag at PNAS. PMID- 2916122 TI - NIH: calling all alumni. PMID- 2916123 TI - Rifkin battles gene transfer experiment. PMID- 2916124 TI - The manganese site of the photosynthetic water-splitting enzyme. AB - As the originator of the oxygen in our atmosphere, the photosynthetic water splitting enzyme of chloroplasts is vital for aerobic life on the earth. It has a manganese cluster at its active site, but it is poorly understood at the molecular level. Polarized synchrotron radiation was used to examine the x-ray absorption of manganese in oriented chloroplasts. The manganese site, in the "resting" (S1) state, is an asymmetric cluster, which probably contains four manganese atoms, with interatomic separations of 2.7 and 3.3 angstroms; the vector formed by the 3.3-angstrom manganese pair is oriented perpendicular to the membrane plane. Comparisons with model compounds suggest that the cluster contains bridging oxide or hydroxide ligands connecting the manganese atoms, perhaps with carboxylate bridges connecting the 3.3-angstrom manganese pair. PMID- 2916125 TI - Control of enzyme activity by an engineered disulfide bond. AB - A novel approach to the control of enzyme catalysis is presented in which a disulfide bond engineered into the active-site cleft of bacteriophage T4 lysozyme is capable of switching the activity on and off. Two cysteines (Thr21----Cys and Thr142----Cys) were introduced by oligonucleotide-directed mutagenesis into the active-site cleft. These cysteines spontaneously formed a disulfide bond under oxidative conditions in vitro, and the catalytic activity of the oxidized (cross linked) T4 lysozyme was completely lost. On exposure to reducing agent, however, the disulfide bond was rapidly broken, and the reduced (non-cross-linked) lysozyme was restored to full activity. Thus an enzyme has been engineered such that redox potential can be used to control catalytic activity. PMID- 2916126 TI - Physiological constraint on feeding behavior: intestinal membrane disaccharidases of the starling. AB - Animals clearly choose what they eat and can even choose among chemically different sugars. The physiological and biochemical mechanisms that constrain feeding choices are largely unknown. In this study, European starlings (Sturnus vulgaris) preferred mixture solutions of D-glucose plus D-fructose to equimolar (double molar caloric value) solutions of sucrose. Intubation feeding of sucrose did not increase blood glucose levels. Sucrose is a useless energy source for these birds because they lack a single digestive enzyme (sucrase) on the small intestinal brush border membrane. However, the membranes possessed separate maltase and isomaltase disaccharidases. This expression pattern and expression patterns of membrane disaccharidases among mammals suggest a role for intestinal enzymes in the coevolutionary interactions between vertebrates and their plant food sources. PMID- 2916127 TI - Nimodipine facilitates associative learning in aging rabbits. AB - Nimodipine is one of several dihydropyridines that block calcium channels. Originally administered to improve cerebral blood flow in elderly patients with chronic cerebrovascular disorders, nimodipine was noted to facilitate learning. These observations led to the present investigation of the effects of nimodipine on associative learning in aging rabbits. Nimodipine accelerated acquisition of conditioned eye-blink in both young and aging rabbits without altering the amplitude of responses to the conditioned or unconditioned stimuli or causing nonspecific responding. Thus, nimodipine may be a candidate for an effective treatment for age-related learning deficits. PMID- 2916128 TI - Overexpression of transforming growth factor alpha in psoriatic epidermis. AB - Transforming growth factor alpha (TGF-alpha) is produced by and required for the growth of epithelial cells and is angiogenic in vivo. Since epidermal hyperplasia and angiogenesis are hallmarks of psoriasis, TGF-alpha gene expression was analyzed in epidermal biopsies of normal and psoriatic skin. TGF-alpha messenger RNA and protein are much more abundant in lesional psoriatic epidermis than in normal-appearing skin of psoriatic patients or in normal epidermis. In contrast, messenger RNA levels of transforming growth factor beta 1 (TGF-beta 1), which inhibits epithelial cell growth, are not significantly different in normal, uninvolved, and lesional psoriatic epidermis. Thus, psoriatic epidermal hyperplasia may involve increased expression of a keratinocyte mitogen (TGF alpha) rather than deficient expression of a growth inhibitor (TGF-beta 1). PMID- 2916129 TI - [Conservative treatment of distal radius fractures. Results of a retrospective study]. AB - Between 1 January 1984 and 31 December 1986, 175 patients with a total of 178 distal radius fractures were treated conservatively in our department. An average of 25 months after the accidents, 124 patients with 126 fractures (71%) were re examined. Wrist function was good or excellent in 52.4%, fair in 41.3% and bad in 6.3% of the patients studied. Anatomical results were slightly better, with the patients' subjective evaluation markedly better. The results are analysed and the causes of the unsatisfactory results pointed out. Thereafter, the indications for conservative treatment are discussed and a regimen presented. Conservative treatment alone is not justifiable. PMID- 2916130 TI - [Chronic fibular ligament insufficiency at the upper ankle joint. Late results after modified Watson-Jones plastic surgery]. AB - The findings at clinical and roentgenological follow-up examination of 44 patients are reported to illustrate the long-term results of a modified Watson Jones technique up to 90 months after the operation. The clinical results (86.3% of the patients without complaints and 88.6% with subjective stability of the ligaments) correspond with those given by a variety of sources in the literature. The roentgenological examination, on the other hand, showed signs of grade I or II arthrosis (Bargon scale) in 61.3% of cases, and arthrosis was worse than before the operation in nearly all cases. The patients in the group, that had received more conservative treatment with an average 6.3 years between lesion and surgical treatment (group 1), had the highest incidence of arthrosis, with 73.6%. In 10 cases the clinical examination revealed reduced supination and dorsiflexion attributable to the tenodesis effect associated with the Watson-Jones technique. In view of the high rate of arthrosis, younger patients and patients with a short tendon part of the peroneus brevis muscle should be treated by another, more "physiological" method. PMID- 2916131 TI - [Luxatio humeri erecta. A rare form of inferior shoulder dislocation]. AB - In patients with erect dislocation of the shoulder, the arm is typically locked in an upright position. This rare variant of subglenoid luxation always causes damage to the ligamentous structures of the joint and sometimes additional complications arise from neurovascular lesions. Two recent cases are reported here. The mechanism of injury, therapeutic measures and prognosis are discussed. PMID- 2916132 TI - [Stress fracture of the femoral neck in a marathon runner. Case report and review of the literature]. AB - Stress fracture of the femoral neck is rare, and the conditions in which it occurs are complex. An unusually high, rhythmically acting force resulting from body weight and muscle tension leads to decompensation of the dynamic equilibrium otherwise prevalent in bone metabolism in conditions of adaptation. Even small differences in leg length predispose to fracture of the longer leg, owing to the increased muscular activity. Bone scanning is helpful in diagnosis when no signs of fracture are revealed by conventional radiography. Internal fixation that will allow weight-bearing should be attempted. In this case report an instance of this type of fracture in a marathon runner is presented. PMID- 2916133 TI - [Flexion-distraction injuries of the thoracolumbar spine with complete pancreatic rupture. Description of a case]. AB - A case is reported of an unstable fracture dislocation of the thoracolumbar vertebral column combined with complete rupture of the pancreas. This combination of injuries is rarely encountered but is dangerous in severely injured patients. Rapid and decisive operative treatment of both injuries should be performed, whereby adequate treatment of the pancreatic rupture has the highest priority. PMID- 2916134 TI - [Simultaneous bilateral spontaneous rupture of the quadriceps tendons compared with unilateral traumatic rupture]. AB - A rare case of simultaneous, bilateral and spontaneous rupture of the quadriceps tendons is described in a 59-year-old man without systemic disease or traumatic lesions. For comparison, we report the case of a young woman with complete traumatic, unilateral rupture of the quadriceps tendon. The more or less normal degenerative changes of the ligament structure were considered to be the additional etiological reasons for both ruptures. A review of the literature is given. PMID- 2916135 TI - [Fatal hangman's fracture]. AB - Delay in the diagnosis of cervical fractures can result in permanent neurological deficits. The circumstances in which the primary assessment of the unconscious patients takes place are often inadequate, and associated visible injuries are of more concern. The pressure to achieve resuscitation leads to an unacceptable level of missed injuries. The tragically delayed diagnosis of hanged man's fracture after suturing of a tracheal rupture made reduction and stabilization of the cervical spine impossible. PMID- 2916136 TI - [Fibular ligament rupture during growth]. AB - In comparison with injuries sustained in adult life, ruptures of the fibular ligaments before growth is complete are more frequently characterized by chondral, osseous and periosteal loosening, which was seen up to the 14th year of age in about 50% of our own population of 129 patients up to the 16th year of life. The average age of patients with osseous and chondral lesions was clearly lower than that of those with periosteal injuries, which was lower than that of patients with inter-ligament ruptures. Accidents at school and during school sports classes were the most frequent cause, being involved in more than 50% of cases; of the various kinds of sport engaged in soccer was the most frequent cause, accounting for 28.8% of all cases. Manual examination of ligamentous stability compared with the opposite side by roentgenoscopy without anaesthesia has proved its worth for a definite diagnosis in fresh injuries. In all cases of evident ligamentous instability operative treatment was indicated, with subsequent immobilization with a plaster cast for 6 weeks. Stable healing of the ligament and a good functional result in all cases as well as a very low rate of complications vindicate this management. Conservative therapy, especially in the age group with normally high activity levels, is now considered correct only in exceptional cases or when operative treatment is refused. PMID- 2916137 TI - Score one for family practice. PMID- 2916138 TI - Eye injury: prevalence and prognosis by setting. AB - Although an estimated 1 million Americans suffer ocular injuries each year, the setting of injury and its prognostic implications have not been closely examined. Using data compiled by the Eye Injury Registry of Alabama (EIRA) from 514 cases of serious eye injury, we examined the demographics and prognosis of ocular injury by setting of injury. Work-related injuries accounted for only 28% of total injuries, and injuries occurring at home accounted for 27%, followed by situations related to recreation (25%), assault (11%), travel (5%), and "other" (school, unknown, etc) (4%). The poorest initial vision, poorest final vision, and highest rate of enucleation occurred in patients injured by assault, whereas the lowest rate of enucleation and loss of light perception was found in patients who had work-related injuries. Patients in the "other" category had the highest rate of return to 20/100 or better vision. PMID- 2916139 TI - Sleep apnea: morbidity and mortality of surgical treatment. AB - We have analyzed the complications in 132 patients who had surgical treatment of sleep apnea or excessive snoring. In this series there were 34 (26%) complications and two patients (1.5%) died. Complications related to uvulopalatopharyngoplasty in 126 patients included rhinolalia (2%) and oropharyngeal hemorrhage (6%). In the 41 patients who had tracheostomy, complications included hemorrhage from tracheostomy (5%), tracheomalacia (5%), peristomal infection (15%), tracheostomy tube intolerance (Montgomery tube 100%, Shiley tube 7%), pneumonia (2%), hypoxia necessitating emergency tracheotomy (2%), and other perioperative complications. PMID- 2916140 TI - Evaluation of antibacterial sensitivity testing methods for methicillin-resistant Staphylococcus aureus in a dermatology outpatient population. AB - Over a period of one year, 1986-1987, 116 strains of Staphylococcus aureus were isolated from patients attending two outpatient dermatology clinics in Houston, Texas. The purpose of this study was to evaluate the adequacy of routine antibiotic sensitivity testing methods for detecting methicillin-resistant Staphylococcus aureus (MRSA). The Kirby-Bauer disk diffusion method was compared with a commercially available screening medium containing 6 micrograms/ml of oxacillin and 4% NaCl. The minimal inhibitory concentration (MIC) of methicillin, oxacillin, and oxacillin with 4% NaCl to S aureus using the agar dilution method was also determined. Approximately 90% of S aureus strains produced beta lactamase and were resistant to penicillin and ampicillin. By disk diffusion, no strains were resistant to methicillin, though diameters of zones of inhibition were between 10 and 14 mm in seven strains. All strains proved to be sensitive to methicillin by MIC determinations and on the oxacillin-NaCl screening medium. The MIC of methicillin was 2.5 micrograms/ml for the majority of strains of S aureus, between 0.16 and 0.31 microgram/ml for oxacillin, and 0.08 to 0.16 microgram for oxacillin with 4% NaCl. We concluded that the incidence of MRSA in an outpatient dermatology population is low, and a combination of disk diffusion and oxacillin NaCl screening is adequate for testing sensitivity. PMID- 2916141 TI - Obstruction of the small bowel in the early postoperative period. AB - To analyze factors related to etiology, diagnosis, and outcome, we reviewed the records of 26 patients in whom a clinical picture of small bowel obstruction developed within one month after abdominal surgery. The initial operation was an emergency procedure in 20 cases and an exploratory laparotomy after trauma in 11. The colon was the organ most commonly operated upon initially, being involved in ten procedures (38%), all of which were emergencies. The clinical diagnosis of bowel obstruction was made within ten days postoperatively in most cases. Surgical reexploration was required in 15 patients (58%), whereas the obstructive symptoms resolved with nasogastric suction in 11. Two patients, both of whom survived, required resection of strangulated bowel; in both a treatment delay of at least 72 hours was documented. There were two deaths (8%), neither of which was directly related to the bowel obstruction. Diagnosis of this clinical entity requires a high index of suspicion, especially after emergency procedures that involve the colon. Optimal survival is achieved by prompt recognition and early intervention when a mechanical bowel obstruction is suspected in the early postoperative period. PMID- 2916142 TI - Lower limb embolus: a near-lethal disease after age 75 years. AB - Because it has been suggested that embolectomy increases morbidity and mortality, we reviewed our experience with lower-extremity embolectomy in an elderly high risk population. Of 153 consecutive patient records reviewed, 69 were sufficiently complete for analysis. Of these patients, 45 were men with a mean age of 80.7 years (range, 75 to 91 years); 24 were women with a mean age of 76.9 years (range, 75 to 81 years). Records were reviewed for patient age, sex, race, acute myocardial infarction or atrial fibrillation upon admission, history of smoking, diabetes, and cardiac disease (acute and chronic), admission blood pressure, role of postoperative echocardiography, and New York Heart Association classification (NYHA class). All patients were hemodynamically stable at the time of operation. Forty-two of the 69 patients had a history of smoking, nine were diabetic, and 48 (33 men and 15 women) had hypertension (blood pressure greater than 140/90 mm Hg) on admission. Twelve deaths occurred within the perioperative period. Nine patients had an acute myocardial infarction and 12 had arrhythmias on admission. Thirty patients (15 men and 15 women) were in NYHA class III. A total of 30 patients had died by six months postoperatively, 27 of cardiovascular causes. The perioperative mortality was 12/69 (17%), and long-term mortality was 30/69 (43%). Simultaneous embolus and myocardial infarction was associated with 100% mortality for the patients surviving the operation; 15 patients required another operation for amputation (nine above-knee and six below-knee). PMID- 2916143 TI - Reduction mammaplasty: central cone technique for maximal preservation of vascular and nerve supply. AB - Many types of breast reduction procedures have been described and are now being used. Before 1984, we used variations of the Wise technique, with free grafting of the nipple-areola complex; because of problems with inadequate nipple projection, squareness of the breasts, and decreased nipple sensation, however, we have subsequently used the central cone technique, as advocated by Hester et al. We present 44 cases with follow-up periods extending up to three years. PMID- 2916144 TI - Immediate prediction of blood requirements in trauma victims. AB - Current recommendations for the management of trauma victims include immediate crossmatching of 4 to 6 units of blood. Unused crossmatched blood is withdrawn from the available blood pool for 48 hours and costs the patient $33 per unit. Growing blood shortages and increasing laboratory costs demand reexamination of this practice. The purpose of this study was to examine blood usage in trauma victims and to develop new guidelines for emergency room requests for blood. The following clinical variables were reviewed in 250 trauma victims to determine their value as predictors of blood usage: age, sex, mechanism of injury, initial vital signs, trauma score (TS), and injury severity score (ISS). The best predictor of blood use was the trauma score. Of the total group, 71% had a TS greater than 14; 91% of these patients did not require transfusion. Twenty-eight percent of the total group had a TS equal to or less than 14; 70% of these patients did require transfusion. The data strongly suggest that type and screen can safely replace type and crossmatch as the initial blood bank requests in patients with trauma scores greater than 14. Blood requirements in patients with a trauma score less than or equal to 14 continue to warrant immediate crossmatching. PMID- 2916145 TI - Significance of a positive Papanicolaou smear in a well screened population. AB - Of 35,937 gynecologic cytology specimens obtained from the cervix or vagina at our institution during a three-year period, 18 (0.05%) were reported as malignant; ten of these 18 (56%) positive results were due to carcinoma arising from sites other than the cervix or vagina. The site of the primary lesion was the endometrium in four patients, the ovary in three, the colon in one, and the breast in one; in one patient the site of the primary carcinoma was unknown. In our patient population a a positive Papanicolaou smear was more often indicative of a noncervical than a cervical malignancy. In addition to detecting preinvasive and invasive malignancies of the cervix and/or vagina, an annual cytologic smear may hasten the detection of extravaginal primary carcinomas. PMID- 2916146 TI - Oxytocin, vasopressin, and prolactin responses associated with nipple stimulation. AB - Nipple stimulation by pregnant women close to term results in oxytocin release, as reflected by increased levels of oxytocin in peripheral plasma. This appears to be a specific response, and it does not involve either vasopressin or prolactin release. PMID- 2916147 TI - Radionuclide thyroid studies: analysis of use and correlation with physical findings. AB - We assessed all thyroid radionuclide studies done at a single institution during one year and evaluated the indication for ordering each study as well as the concordance of study results with those of physical examination. We found that thyroid radionuclide imaging was overused, with at most 66% of scans being indicated (using the most generous classification of a proposed rating for indications). Radioactive iodine uptake measurement done without scanning was probably underused. Concordance between the results of physical examination and scanning was reflected by an overall agreement rate of 51%; agreement between results of scanning and physical examination beyond what might be expected by chance alone was reflected by a kappa value of .34. Concordance was strongest for diffuse goiters and weakest for normal findings. PMID- 2916148 TI - Autonomously functioning thyroid nodule. AB - We report 408 cases of autonomously functioning thyroid nodule (AFTN); 85.5% occurred in female patients, for a male-female ratio of 1:6. Eighty-nine patients (21.8%) were hyperthyroid, 76 of them being female, also yielding a male-female ratio of 1:6. There was a linear increase in the incidence of hyperthyroidism with age and with an increase in the size of the nodule, especially for nodules more than 3 cm in diameter. There was a significantly higher incidence of hyperthyroidism for nodules of the same size when they occurred in patients more than 40 years of age. There was a corresponding increase in hyperthyroidism with an increase in the length of time after the initial detection of the nodule; this finding was significantly greater in patients more than 40 years of age. Thus, the age of the patient was found to be a more important determinant in the production of hyperthyroidism associated with an AFTN than either the size of the nodule or the duration of symptoms. PMID- 2916149 TI - Factitious disorder with physical manifestations: pitfalls of diagnosis and management. AB - Munchausen's syndrome is a chronic form of factitious disorder in which fabricated physical manifestations are used to attain multiple hospital admissions. Patients with this disorder are exposed to unnecessary invasive studies, and their entire life may come to revolve around attainment of hospitalization. In addition, medical personnel are subjected to confusion and frustration, scarce resources are wasted, and institutions are left with enormous unpaid bills. Using an illustrative case, we demonstrate pitfalls in the diagnosis and management of these patients, with emphasis on breaking the cycle of repeated hospitalizations, and discuss the enormous human and economic costs of their insatiable quest for medical attention. PMID- 2916150 TI - Intussusception revisited: clinicopathologic analysis of 261 cases, with emphasis on pathogenesis. AB - In the ten-year period from 1978 through 1987, 261 patients with intussusception were admitted to Chang Gung Memorial Hospital. The diagnosis was established by barium enema or at laparotomy. The patients were divided into two groups; there were 228 children ranging in age from 1 month to 14 years, and 33 adults. Among the children, 134 (59%) were male and 94 (41%) were female, a ratio of 1.4:1. There was no clear seasonal incidence. The age group most commonly affected was between 3 and 11 months of age (72.4%). The classic triad of abdominal pain, vomiting, and rectal bleeding was encountered in 187 cases (82%). Two hundred one cases (88%) were idiopathic, without any definite leading point. In these cases, the ileocecal area was the site most commonly involved (82%), hypertrophic Peyer's patches of the terminal ileum being responsible for 39% of the idiopathic intussusceptions in the ileocolic area. Enlargement of the mesenteric lymph nodes occurred in 67 of the idiopathic cases (33%). Local pathology or the leading point precipitating intussusception was found in 27 cases (12%); there were eight benign tumors, six malignant tumors, and 13 tumor-like lesions. In 32 of the 33 cases in adults, there was a definite contributing pathologic entity, including 18 benign tumors, 11 malignant tumors, and three tumor-like lesions. In infants and young children, there is usually no apparent predisposing disease, and a contributing or causative local pathologic lesion is seldom found. In contrast, intussusception in adults is almost invariably caused by some preexisting lesion involving the bowel wall. Furthermore, trauma, lymphoid hyperplasia, pregnancy, and viral infection may be possible predisposing factors in the production of intussusception. PMID- 2916151 TI - Recurrent meningitis in a black man. AB - A 43-year-old black man had recurrence of acute bacterial meningitis caused by Neisseria meningitidis. He had had three previous episodes of acute meningitis, starting at age 27 years. The patient's serum was found to have an undetectable level of the sixth component of complement. Congenital absence of one of the terminal proteins in the complement system impairs a patient's ability to eradicate bacteria, and increases susceptibility to recurring infections caused by meningococci and other Neisseria species. Though the serum of complement deficient patients promotes normal opsonization of bacteria, it is unable to kill meningococci directly. The currently available meningococcal vaccine may augment type-specific antibody, but it does not correct the underlying complement deficiency. The role of self-administered antibiotics in preventing recurrent Neisseria infection remains uncertain. PMID- 2916152 TI - Janace. PMID- 2916153 TI - Testicular feminization syndrome: a case study of four generations. AB - This report deals with the complete form of testicular feminization in four generations of a single kindred. The four siblings who have had orchiectomy had no evidence of testicular malignancy. Because all four of the postpubertal patients have the complete form of the disorder, the prepubertal member is being managed expectantly, awaiting the onset of female secondary sexual characteristics at puberty. Other carriers may be identified as reproductive function continues. PMID- 2916154 TI - Choledochal cyst. AB - A 16-year-old girl with recurrent pain in the right upper quadrant and abnormal results of liver function tests was found to have a large choledochal cyst filled with stones. Computerized tomography and endoscopic retrograde cholangiopancreatography showed the large cyst with innumerable primary cyst stones and an anomalous pancreaticobiliary duct junction. PMID- 2916156 TI - Mycotic aneurysm of the inferior pancreaticoduodenal artery: successful nonoperative management. AB - Although mycotic aneurysms of small visceral arteries are rare, they have a high morbidity and mortality due to rupture and sepsis. Any patient with abdominal pain and bacterial endocarditis should be suspected of having a mycotic aneurysm. Selective arteriography confirms the diagnosis. In the case we have reported, diagnosis of a mycotic aneurysm of the inferior pancreaticoduodenal artery was established by angiography, and the patient was treated by percutaneous transcatheter embolization. This case demonstrates that mycotic aneurysms of small visceral arteries may be managed nonoperatively with antibiotics and percutaneous transcatheter embolization therapy. PMID- 2916157 TI - Intervertebral diskitis due to Candida tropicalis. AB - This report describes a case of Candida tropicalis intervertebral diskitis successfully treated with a brief course of amphotericin B followed by a longer course of ketoconazole. Candida tropicalis is an increasingly frequent pathogen in immunocompromised patients, and infection can become manifest weeks or months after an episode of neutropenia has resolved. The excellent response we observed in this patient adds to a growing body of clinical experience testifying to the effectiveness of ketoconazole in treating certain deep-seated candidal infection. PMID- 2916155 TI - Azygos continuation of the inferior vena cava masquerading as neoplasm. AB - The two cases we have reported demonstrate that dramatic enlargement of the azygos vein may occur in patients with azygos continuation of the inferior vena cava. Awareness of this phenomenon can prevent unnecessary procedures. The diagnosis should be established by dynamic CT scan. PMID- 2916159 TI - Factors influencing postoperative gastric emptying. PMID- 2916158 TI - Antenatal diagnosis of Candida chorioamnionitis. PMID- 2916160 TI - Coccidioidomycosis versus pollen. PMID- 2916161 TI - High-frequency deletion event at aprt locus of CHO cells: detection and characterization of endpoints. AB - Two mechanisms are implicated in generating recessive drug resistance mutants at the adenine phosphoribosyltransferase (aprt) locus of Chinese hamster ovary (CHO) cells, one of which is a spontaneous high-frequency deletion of the entire gene. We have isolated and mapped a 19-kb fragment carrying aprt and its flanking sequences. A Southern blot study of 198 independent deletion mutants revealed that two different mutants have one of their breakpoints within the 19-kb region analyzed. One of these has an upstream breakpoint which could be narrowed down to a 4-kb fragment containing repetitive sequences. The other mutant has a breakpoint within a 410-bp sequence located 8.5 kb downstream of the aprt gene and which carries several elements similar to those signaling V-(D)-J joining in immunoglobulin and T-cell receptor gene rearrangements. In each case the other breakpoint lay outside of the analyzed region. These results support the previous indications that the deletions created by this spontaneous event are large. PMID- 2916162 TI - Two types of mouse FM3A cell mutants deficient in 5-aminoimidazole-4-carboxamide ribonucleotide transformylase and their transformants isolated by human chromosome-mediated gene transfer. AB - We isolated three adenine auxotrophic mutants (Ade1, Ade2 and Ade3) of mouse FM3A cells deficient in 5-aminoimidazole-4-carboxamide ribotide transformylase (EC 2.1.2.3) activity. Ade1 and Ade3 but not Ade2 also lacked inosinicase (EC 3.5.4.10) activity. While Ade2 and Ade3 complemented each other, Ade1 complemented neither Ade2 nor Ade3, suggesting that two complementation groups exist in these mutants. We introduced human genes into the Ade2 and Ade3 cells by chromosome-mediated gene transfer. All the transformants tested were found to produce the human transformylase and inosinicase, and identical DNA bands containing human Alu sequences were detected in the transformants of Ade2 and Ade3. These mutants seem to have arisen by mutation in the same gene or adjacent genes, since only human chromosome 2 was capable of rescuing the genetic defects in all these mutants. PMID- 2916163 TI - Genetic analysis of XR-1 mutation in hamster and human hybrids. AB - We investigated the dominant/recessive nature of the XR-1 mutant locus in intraspecies Chinese hamster ovary (CHO) hybrids and interspecies hybrids with human cell lines that possess different radioresistances. The XR-1 cell is abnormally sensitive to killing by gamma rays in the G1 phase of the cell cycle, while late-S-phase cells have wild-type resistance. [3H]Thymidine selection was used to eliminate the resistant S-phase population. In both intraspecies and interspecies hybrids, the XR-1 mutation is recessive to the wild-type cell and is not influenced by differences in chromosome ploidy. Analysis of hybrids between human ataxia telangiectasia fibroblasts AT5BI and XR-1 cells revealed that they possess different genetic defects as they complemented each other in three of four hybrids tested. These data suggest that the XR-1 locus is evolutionarily conserved between hamster and human cells. PMID- 2916164 TI - Hyal-1, a locus determining serum hyaluronidase polymorphism, on chromosome 9 in mice. AB - Analysis of mouse serum hyaluronidase by polyacrylamide gel electrophoresis, with the substrate high-molecular-weight hyaluronan (hyaluronic acid) included in the gel performed in mice of two different strains, BALB/cBy and C57BL/6By, reveals a pattern of multiple enzyme forms specific for each genotype. In BALB/c serum, seven different forms are present, only one of which is found in C57BL/6 serum. Segregation analysis of the enzyme polymorphism in backcross progeny and in recombinant inbred and bilineal congenic lines shows that the difference is due to a single locus, which we have designated as Hyal-1. Hyal-1 is linked to the histocompatibility locus H-7, on chromosome 9. PMID- 2916166 TI - Regional localization of CCG1 gene which complements hamster cell cycle mutation BN462 to Xq11-Xq13. AB - The human CCG1 gene, which complements the temperature-sensitive hamster cell cycle mutations BN462 and ts13, has recently been cloned and shown to be located on the X chromosome. We have used somatic cell hybrids segregating portions of multiple X--autosome translocations to localize this gene to the Xq11 to Xq13 region of the human X chromosome. PMID- 2916165 TI - Single-step selection of mammalian cell mutants deficient in CTP synthetase. AB - A single-step selection of Chinese hamster V79 cells deficient in CTP synthetase (CTPS-) is presented. The underlying principle of the direct selection is the differential and efficient killing of synchronized wild-type cells through incorporation of [3H]uridine and [3H]thymidine. The CTPS- mutant cells were recovered by virtue of their not engaging in DNA synthesis, because (1) CTPS- cells are deficient in CTP synthetase and thus are unable to convert [3H]UTP into [3H]CTP, which eventually is converted into [3H]dCTP and incorporated into DNA; (2) the growth of CTPS- mutant cells was arrested as a result of cytidine deprivation, thus escaping the killing by the incorporation of [3H]thymidine. The isolated mutant clones are auxotrophic for cytidine and are stable in phenotype with a reversion frequency of less than 1 x 10(-7). The mutant cells have no or very low CTP synthetase activity when tested by in vitro CTP synthetase assay or by whole-cell [3H]uridine labeling assay. This modified "tritium suicide" method combined with the S-phase cell synchronization could provide a powerful means for the recovery from the cell population of nondividing mutant cells that are auxotrophic for some special nutrient requirement. PMID- 2916167 TI - The early diagnosis and prevention of oral precancer and cancer. PMID- 2916168 TI - Clinical manifestations of oral precancer and cancer. AB - Oral squamous cell carcinomas generally metastasise early and are associated with a poor survival rate. Their prevention depends largely on timeous identification of precancerous oral mucosal lesions, which may present clinically as a homogeneous or nodular white plaque (leucoplakia), a mixed white and red lesion (erythroleucoplakia) or a homogeneous or nodular red lesion (erythroplakia). Red premalignant lesions generally have a higher malignant potential than white lesions. PMID- 2916169 TI - [Radiotherapy of esophageal carcinoma: an assessment of patients treated at Tubingen from 1977 to 1982]. AB - We report on the results of therapy of 116 patients with esophagus carcinoma. The patients have been attended to at the Medical Radiation Institute of Tubingen between 1977 and 1982. In 95 cases sole radiation was performed as operation was impossible. The other patients underwent a combined surgical-radiotherapeutical treatment. The joint doses of radiation applied ran from 50 to 70 Gy in five to seven weeks' time. In particular we considered the total survival rate according to tumor stage, the local tumor control and the period until relapse. 22% of the primarily irradiated patients achieved complete remission, 42% reached particular remission and 15% achieved minimal tumor remission (total response rate: 79%). Merely in 8% of the cases the tumor did not respond perceptibly. In the other cases irradiation had to be interrupted because of general worsening, or the patients got lost to post-therapeutical observation. The total survival rates, all stages taken into account, arose as follows: one year: 36.8%, two years: 12.6%, five years: 7.3%. After sole radiotherapy in 67% of the cases which had a radiologically verified relapse more than six months passed by before a local recurrence tumor was stated. The bad prognosis of the esophagus carcinoma, as demonstrated in literature, is entirely confirmed-the negative selection of our patients taken into account. The high rank of radiotherapy in achieving effective palliation is emphasized. PMID- 2916170 TI - [The results of radiotherapy in advanced oral carcinomas. The effect of altered therapeutic strategies]. AB - During the period from 1968 through 1984, 197 patients with advanced carcinomas of the oral cavity have been irradiated. The authors investigate the influence of a standardized chemotherapy as initial therapy measure on the subsequent radiotherapy and the therapy results. Whereas 4.2% of patients were submitted to this treatment between 1968 and 1975, 64.5% of patients received a chemotherapy during 1976 and 1984. The remission rate following to cytostatic therapy was 71%; most of them were partial remissions. The influence of chemotherapy manifested itself by an increase of macroscopically radical tumor resections, especially in stage IV, but also by an increased number of radiotherapy interruptions in case of strong mucosal reactions. An increase of the median survival time from 20 to 30.5 months was connected with the intensified therapy. Further on, this difference vanished, and the five-year survival rates were identical. PMID- 2916171 TI - The role of combined composite resection and irradiation in the management of carcinoma of the oral cavity and oropharynx. AB - Squamous cell carcinoma of the oral cavity and oropharynx can invade the mandible requiring an "en bloc" or composite resection. With this procedure alone, reported local control rates for advanced stage tumors have been suboptimal suggesting the need for adjuvant therapy. The treatment records of 35 patients were reviewed who were treated with composite resection alone, composite resection plus radiotherapy, or composite resection as a salvage procedure for a primary treatment failure. Combined irradiation and composite resection resulted in a higher local control than patients receiving composite resection alone (72% vs. 43%). There was no difference in complication rates between these two treatment groups. Composite resection as a salvage procedure resulted in local control in 38% of patients through this was associated with a 64% rate of complications. This data and a review of the literature suggest that tumors of the oral cavity and oropharynx with extension to the mandible requiring composite resection probably represent a category of tumors with a high risk of local recurrence and may benefit from adjuvant irradiation. PMID- 2916172 TI - [Accelerated irradiation of bone metastases]. AB - In a prospective study, accelerated irradiation was performed over 60 portals in 34 tumor patients with peripheral bone metastases. During a period of three days, three daily fractions of 3 Gy each were applied with intervals of four hours, resulting in a total dose of 27 Gy. Using this fractionation schedule introduced by Ammon, a reduction of metastasis-associated pain was achieved in 90% of cases (54/60). The onset of pain reduction was observed earlier than seen with conventional fractionation schedules (five fractions of 2 Gy each per week, total dose 40 Gy). With regard to objective treatment effects, no significant difference was found between accelerated irradiation and conventional fractionation, the rate of remineralization being 43% (26/60), and the rate of stabilization of formerly progressive bone destructions being 55% (33/60). Accelerated irradiation was tolerated well usually. Marked acute side reactions occurred in only one case with metastatic involvement of joint and reaction of synovia. The major advantage of accelerated irradiation is the shortening of the total treatment period and the consequent reduction of treatment stress in patients with advanced cancer. PMID- 2916173 TI - [Flow cytophotometric measurements before and during radiotherapy of head and neck tumors]. AB - The DNA index and proliferation activities were determined by flow cytophotometry in 59 tumors of the head and neck area. 35 tumors (59%) were aneuploid, 24 (41%) were diploid. Aneuploid tumors showed a tendency to increased formation of lymph node metastases, an increased risk of relapse as well as a shorter relapse-free interval. No correlation was found between the primary tumor stage and the incidence of aneuploid tumors. Whereas aneuploid tumors developed frequently regional recurrences, only local recurrences were observed in diploid tumors. A number of biopsies was additionally performed during radiotherapy in twelve tumors. After 10 or 20 Gy, aneuploid tumors showed a considerably increased number of S and S2 + M phase cells. In diploid tumors, substantial modifications of the cell cycle phases were not found, because it is not possible in these cases to distinguish between normal cells and tumor cells. PMID- 2916174 TI - [Irradiation of TSH-secreting hypophyseal adenomas]. AB - Hypophyseal adenomas secreting TSH are very rare. In dependence on local symptoms, internal-endocrinological, neurosurgical, or radiotherapeutical treatment approaches are applied alone or in combination. A case of radiotherapy alone is presented which was performed successfully in a patient with TSH secreting hypophyseal adenoma. This case is compared with the rates of success of other therapy modalities by means of a detailed literature survey. PMID- 2916175 TI - [Rotational irradiation with a centrally placed block]. AB - A rotational field technique with a central placed block generates nearly circular isodoses with a pronounced minimum in its center, comparable with a cone shaped mountain with a crater. The shape of both, mountain and crater, can be effectively varied by means of block size, field size, rotational angle and by superimposing two different types of rotational fields. One application of this radiation technique is the myelon-sparing treatment of the neck, another one the percutaneous completion of an intracavitary pre-radiation in the case of a gynecologic cancer. PMID- 2916176 TI - Pancreatitis caused by congenital anomalies of the pancreatic ducts. PMID- 2916177 TI - Ductal drainage for chronic pancreatitis. AB - The operative experience of 23 patients with chronic or chronic relapsing pancreatitis who underwent ductal drainage is reviewed. All of those studied were treated for pain directly related to their pancreatitis and had no evidence of pseudocyst. Each patient was followed up for a minimum of 5 years postoperatively. In those persons with a diffusely dilated duct or "chain of lakes" pattern seen on ERCP, ductal drainage was preferred to pancreatic resection because of lower mortality and preservation of endocrine function. Internal ductal drainage as described by Partington, Rochelle, and Thal was the procedure of choice because it provides excellent pain relief and splenectomy is not required. Good or excellent long-term pain relief was achieved in 90% of patients undergoing operative intervention. Ductal drainage was frequently complicated by peptic ulcer disease. Postoperative antacid or histamine blocker therapy is recommended. PMID- 2916178 TI - Clinical and biochemical features in primary hyperparathyroidism. AB - Sixty-one consecutive patients were examined to determine the current mode of presentation of primary hyperparathyroidism (pHPT). Of these patients, 37.7% were asymptomatic, and the initial indication of pHPT was hypercalcemia, which was found unexpectedly on biochemical screening of the serum in elderly patients. Hypertension was twice as common among patients with pHPT as in the general population (36.1%). The next most common presentations were urinary calculi (18%) and mental depression (18%). The most useful discriminant laboratory tests were serum calcium, phosphorus, chloride, and parathormone (PTH). The calculated coefficient of correlation of PTH to land weight was high (r = 0.571, p less than 0.001). There was very significant correlation between PTH and seriousness of bone disease (r = 0.620, p less than 0.001). After parathyroidectomy, 3.3% of patients remained hypercalcemic, 93% were normocalcemic, and 1.6% were hypocalcemic. PMID- 2916179 TI - The incidence of intra-abdominal surgery in acquired immunodeficiency syndrome: a statistical review of 904 patients. AB - This communication concerns the incidence of intra-abdominal surgery in 904 patients with acquired immunodeficiency syndrome who were admitted to the Cabrini Medical Center during a 3-year period from January 1985 to January 1988. It was found that 36, or 4.2%, of the patients underwent surgery, including 12 cholecystectomies, 7 splenectomies, 7 appendectomies, 6 laparotomies, and 6 other operations for miscellaneous conditions. It was pointed out that the high incidence of inflammatory involvement of the gallbladder, appendix, and intestines in AIDS patients was in all probability due to the nature of the blood supply to these organs. All receive blood from terminal arteries or vessels with few anastomoses, and therefore when vasculitis ensues it is often followed by gangrene or ulceration of mucosal surfaces. Surgical intervention was deemed advantageous for those patients with splenomegaly and accompanying pancytopenia, acute appendicitis, and lesions of the gastrointestinal tract, but not for those with cholecystitis. The high postoperative mortality rate, 22.2%, was attributed primarily to the immunodeficient state of the patients rather than to complications of their surgery. PMID- 2916180 TI - Changes in the levels of endogenous antioxidants in the liver of mice with experimental endotoxemia and the protective effects of the antioxidants. AB - Gram-negative bacterial endotoxin (lipopolysaccharide) induces hepatic damage in mice caused by lipid peroxidation, and administration of antioxidants (coenzyme Q10 and alpha-tocopherol) suppresses this lipid peroxidation, preserves energy metabolism, and enhances the survival of endotoxin-administered mice. Therefore experiments were done to determine whether experimental endotoxemia in mice affected the levels of endogenous antioxidants and whether treatment with antioxidants altered these levels. Endotoxin produced decreases in hepatic endogenous antioxidants with time: reduced coenzyme Q9, alpha-tocopherol, and reduced glutathione were lowered to 29.9%, 27.1%, and 45.4% of the control levels, respectively, 24 hours after administration. Exogenously administered coenzyme Q10 (oxidized) accumulated in the liver and showed a maximal plateau between 8 and 16 hours after injection when 82% of coenzyme Q10 was converted to the reduced form. Coenzyme Q10 administered with endotoxin totally or partially prevented the decreases in these endogenous antioxidants, and furthermore, total coenzyme Q10 and the reduced form, both at levels of approximately 30 mg protein, were consumed during the period of elevated lipid peroxidation, 16 hours after endotoxin injection. These results indicate that coenzyme Q10 acts in vivo as an antioxidant after it has been converted to the reduced form. alpha-Tocopherol administered also showed an 84-fold accumulation in the liver 8 hours after injection, completely preventing any decrease in endogenous reduced coenzyme Q9 and partially preventing reduction of glutathione, which indicated an in vivo antioxidant action of alpha-tocopherol. These results support the assumption that administered coenzyme Q10 or alpha-tocopherol functions cooperatively with endogenous antioxidants to prevent tissue damage caused by lipid peroxidation in endotoxemia. PMID- 2916181 TI - Regulation of gallbladder ion transport: role of biliary lipids. AB - Recent studies indicate that biliary lipids influence in vivo gallbladder absorption and solute-coupled water flow. To clarify the electrophysiologic effects that underlie this phenomenon, prairie dog gallbladders were mounted in an Ussing-type chamber, and the influence of bile acids and varying ratios of bile acids and biliary phospholipids on transepithelial potential difference (Vms), resistance (Rt), and short-circuit current (Isc) was examined. Exposure to 5 mmol/L taurodeoxycholate (TDC) resulted in inhibition of Vms (p less than 0.01) and Isc (p less than 0.01) and an increase (p less than 0.05) in Rt. Subsequent perfusion with bile acids and phospholipids (5 mmol/L TDC + 0.3 mmol/L phosphatidylcholine [PC]) led to continued inhibition of ion transport. In contrast, exposure to 5 mmol/L TDC + 1.7 mmol/L PC resulted in a significant increase in transport, as manifested by an increase in Vms (p less than 0.02) and Isc (p less than 0.01) and a decrease in Rt (p less than 0.05) compared with bile acids. These results indicate that the ratio of phospholipids to bile salts modulates ion transport across prairie dog gallbladder and that this ratio may be an important determinant of gallbladder absorption in health and disease. PMID- 2916182 TI - Evidence that epinephrine acutely redistributes blood flow to experimental intrahepatic tumors. AB - Tumor microcirculation was studied in Sprague-Dawley rats with solitary intrahepatic implants of Walker carcinosarcoma tumors. Thioflavine S (TS), a fluorescent dye that stains capillary endothelium acutely, was injected intraportally or intra-arterially in order to demonstrate patterns of blood flow through normal liver tissue and through tumor. The dye was given immediately after intraportal injection of 10 micrograms of epinephrine in some animals and 3 minutes after the epinephrine in others. Control animals received TS alone. Additional animals were given TS immediately after intra-arterial epinephrine. The degree of resulting fluorescence in tumor and liver was graded subjectively from 0 to 3+. In the controls and in animals receiving TS 3 minutes after epinephrine, fluorescence in the centers of tumors was absent or, at most, faintly present. In contrast, all animals given epinephrine either intraportally or intra-arterially immediately before the dye showed intense fluorescent staining within the centers of the tumors. Subjective grading averaged 0.6 +/- 0.1 in the controls, 2.2 +/- 0.1 in those receiving intraportal epinephrine immediately before TS, and 1.0 +/- 0.3 in those receiving TS 3 minutes after epinephrine. Results were significantly higher in the latter group (p less than 0.01). Subjective grading in animals receiving intra-arterial epinephrine immediately before TS averaged 2.5 +/- 0.3. These experiments confirm previous studies in this laboratory that demonstrated an acute short-lived redistribution of blood flow into the centers of intrahepatic tumors after administration of epinephrine. PMID- 2916183 TI - Congenital foramen of Bochdalek's hernia in an infant with obstructive jaundice. AB - A case of infantile obstructive jaundice caused by a right-sided foramen of Bochdalek's diaphragmatic hernia is reported. This association has not previously been reported in an infant. At operation, extrahepatic biliary obstruction was relieved by reduction of the contents of the hernia. This unusual presentation of a right-sided congenital diaphragmatic hernia underscores the usual diagnostic delay seen with such lesions. PMID- 2916184 TI - Pneumoperitoneum and an acute abdominal condition caused by spontaneous perforation of a pyometra in an elderly woman: a case report. AB - Pyometra, a collection of purulent material in the uterus, is an uncommon gynecologic entity. Spontaneous perforation of the uterus is an infrequent complication of pyometra, most often the result of malignant conditions in the uterus. We report the case of an elderly woman who had an acute abdominal condition and pneumoperitoneum due to a ruptured pyometra resulting from a degenerative and infected leiomyoma. Although uterine disease is a rare cause of an acute abdominal condition and pneumoperitoneum in the elderly, a perforated pyometra must be considered in the differential diagnosis. PMID- 2916185 TI - Aberrant right hepatic artery vena cava fistula: a case report. AB - An unusual case of visceral arterial venous fistula between an aberrant right hepatic artery and the inferior vena cava is presented. A critical review of the anatomic relationships in this location offers a plausible explanation to account for the rarity of this type of fistula. The second issue deals with the ligation of the hepatic artery. We caution against hepatic artery ligation, especially when dealing with an aberrant right hepatic artery. PMID- 2916186 TI - Coumarin necrosis or Coumadin necrosis? PMID- 2916187 TI - Autonomously functioning thyroid nodules in childhood and adolescence. PMID- 2916188 TI - Renal failure in the jaundiced patient. PMID- 2916189 TI - Infection during percutaneous transhepatic biliary drainage. PMID- 2916190 TI - [Injuries in alpine skiing]. PMID- 2916191 TI - [Self-poisoning in Northwest Norway in 1975-1984]. AB - During the ten-year period 1975-84, 251 patients were hospitalized because of self poisoning in Nordmore, the northern part of More and Romsdal county. During the five last years, there was a large increase in hospital admittances because of self poisoning, especially of persons below the age of thirty. Men dominated in the age group 20-30 years, and women in the age group 15-20 years. There was a significant correlation between the number of unemployed and the number of self poisonings through out the ten-year period. PMID- 2916192 TI - [Self-poisoning in Northwest Norway in 1984. A follow-up after 6 months. A prospective study]. AB - During the one-year period of study, 37 patients were admitted to the medical department, Kristiansund hospital, because of self poisoning. Mixed intoxications dominated, especially combinations of benzodiazepines and alcohol. One patient died. Interpersonal conflicts were stated as the main reason for the self poisoning. Five patients were considered suicidal. 27 patients were followed up six months later. A majority considered both their social and mental situation to be better than at the time of the self poisoning episode, and had reduced consumption of alcohol and drugs. PMID- 2916193 TI - [Fatal self-poisoning in Western Norway in 1978-1987]. AB - Self-administered poisoning is a common occurrence in a hospital medical department. Fatalities are few when treatment can be given. However, a certain number of deaths do occur outside hospitals--most of them in the patient's home. A forensic examination is usually performed in these cases. In the years 1978-87, 297 deaths from self-administered poisoning were investigated at the Grade Institute, Department of Forensic Medicine, University of Bergen. Alcohol was the most common cause of death. Amongst drug-induced poisonings, tricyclic antidepressants were the most frequent cause of death. PMID- 2916194 TI - [Hybridization in situ. A new technic for the demonstration of viruses and gene products in histologic and cytologic specimens]. AB - The use of in situ hybridization for light-microscopic demonstration of specific DNA or RNA-sequences is illustrated with examples. This method is useful for demonstration of viruses and gene products (mRNA) in individual cells in tissue sections or in cells in suspension. In situ hybridization technology is particularly useful in diagnostic pathology as an adjunct to the conventional methods for infectious diseases. In addition, the method is a powerful tool for analysing the interaction between viral infection and the induction and maintenance of certain human neoplasms. We discuss various aspects of tissue handling, fixation, hybridization procedures and detection of the hybridization signal. We also stress the importance of close cooperation between laboratories in the field of gene technology. PMID- 2916195 TI - [Sudden infant death--the QT interval in ECG and bradyarrhythmias]. AB - Prolongation of ventricular repolarization, as evidenced from an increased QT interval, makes the ventricles more susceptible to fibrillation. The theory has previously been advanced that some cases of sudden infant death syndrome may be due to a non-hereditary QT-prolongation, resulting in fibrillation and cardiac death. This theory has been seriously doubted, since in subsequent long series of recordings in newborns the QT-interval has been found normal at rest. However, the QT-theory has recently been revived by a report that in some babies with sudden infant death syndrome the ability to shorten the QT-interval as the heart rate increases is impaired, an observation which is consistent with the QT theory. The present experiments on infant and adult rodents have shown that during the innate fear paralysis reflex, elicited by a variety of frightening stimuli of a type that commonly occur during ordinary daily life, the QT-interval may be transiently prolonged and is usually associated with bradycardia and changes of the ST-segment and T-wave. The fear paralysis reflex has previously been proposed as a triggering mechanism for SIDS. These findings lend support both to the fear paralysis theory and the QT-theory. The reflex may represent an external cause of QT-prolongation which adds to the intrinsic impairment of repolarization resulting in a condition which favours ventricular fibrillation. A second unfavourable intrinsic factor is chronic hypoxia. PMID- 2916196 TI - [Interprofessional case conferences in connection with child abuse. A resource or a badly used time?]. AB - Interprofessional co-operation and case-conferences in connection with child abuse and neglect are of a special nature. They bring together agencies and partners who have previously not cooperated to any degree, such as health workers and child care workers, and in some cases also the prosecuting authorities. The author argues that such cooperation is necessary, both because of the nature of the abuse and because the different agencies have different areas of responsibility. The article indicates the aims of such case-conferences and discusses problems connected with these meetings, and who should lead them. PMID- 2916197 TI - [Parotid gland tumors. What not to do]. AB - Patients with a tumour located anterior or inferior to the ear probably have a parotid gland tumour. These patients should be referred without further investigation to an ear, nose and throat specialist. Diagnostic measures that may be performed are fine needle aspiration cytology and ultrasonography. Biopsy or enucleation of the tumour should not be carried out. Correct treatment is parotidectomy with preservation of the facial nerve. Inadequate primary treatment may lead to a very unpleasant situation for the patient and for the physician. This is illustrated by three case histories. PMID- 2916198 TI - [Malignant salivary gland tumor. Occurrence, histology, prognosis]. AB - The article is based to some extent upon publications from the ear, nose and throat departments at Rikshospitalet and Ulleval sykehus. For a long time, about 25-30 malignant neoplasms of salivary glands have been diagnosed each year in Norway. Some develop in major salivary glands such as glandula parotis and glandula submandibularis; some in minor salivary glands, most typically in the palate. In this respect glandula sublingualis is of little importance. The purpose of this article is to indicate the prognosis for these malignant neoplasms in the light of therapeutic results reported in this country and abroad. Besides therapeutics, other important factors for the prognosis include localization and histological type. These factors are dealt with separately. The prognosis is found to be best for malignant salivary gland neoplasms of the palate, with a reported five years survival of up to 77%. The next best prognosis is for glandula parotis (46-70%), followed by glandula submandibularis (32-50%). PMID- 2916199 TI - [Splenectomy in hematologic diseases]. AB - We present the results of splenectomy in 45 patients with haematological diseases during the period 1975-85. Of 16 patients with immunologic thrombocytopenia, splenectomy resulted in a satisfactory and sustained platelet elevation in 11 (69%). Splenectomy corrected anaemia in all five patients with hereditary spherocytosis. Of seven patients with autoimmunohaemolytic anaemia, four responded satisfactorily. Postoperative complications occurred in ten of 45 patients (22%). There was no post-operative mortality. Only 49 per cent of the patients had received antipneumococcal vaccination. This is not satisfactory, and all unvaccinated, splenectomized patients should be offered vaccine. If possible, the vaccination should be performed before operation. PMID- 2916200 TI - [The pulmodiaphragmal ligament. An often misinterpreted normal variant]. AB - In some cases the pulmonary ligament extends caudally to the diaphragm, where it blends with the parietal pleura. This anatomical variant is named the pulmodiafragmal ligament. In chest X-ray it gives rise to spikes and unsharp areas in the central part of the diaphragm in the lateral view. The article describes the pulmodiafragmal ligament and its significance by the interpretation of chest X-ray in normal and pathologic states. PMID- 2916201 TI - [Pulmonary edema following airway obstruction]. AB - This case report describes an adult patient who developed post extubation laryngeal spasm and later pulmonary edema following relief of the laryngeal spasm. The mechanism that causes pulmonary edema following upper airway obstruction is very probably due to a modified Muller maneuver (inspiration against a closed glottis), which will increase negative intrapleural pressure, and thereby cause increased pulmonary capillary permeability. PMID- 2916202 TI - [Multicentric Castleman's disease]. AB - We describe a case of histologically proven multicentric Castleman's disease in a 68 year old man. The clinical picture was dominated by severe hemolytic anemia. The outcome was fatal despite active treatment. We discuss the main pathological and clinical characteristics distinguishing multicentric Castleman's disease from the localized variant. The different age distribution, localized versus multicentric disease, different responses to treatment, and outcome, indicate that the two types of Castleman's disease represent different entities presenting common histological features in the lymphoid lesions. PMID- 2916203 TI - [The rehabilitation center in Rauland. Effects of training and treatment]. AB - Attforingssenteret i Rauland (a rehabilitation centre) was opened in May 1986. Three pilot studies were carried out during the period May-December 1986. One of the studies showed some of the epidemiological data concerning work. The second showed the effect of four weeks' stay on psychological parameters. The third demonstrated a significant effect of exercise on aerobic capacity and maximal muscular strength. PMID- 2916204 TI - [The role of lipoproteins and macrophages in the development of atherosclerosis]. AB - Much of the cholesteryl ester that accumulates within atherosclerotic plaques is found within foam cells of monocyte origin. The cholesterol component of these esters is derived from the cellular uptake of plasma lipoproteins that have penetrated into the extravascular space. Monocyte-macrophages take up and degrade native low density lipoprotein (LDL) by the classical LDL (apo B/E receptor) only at rather slow rates. On the other hand, modified LDL is taken up much more rapidly by the scavenger receptor. Modification of LDL possibly involves lipid peroxidation, and antioxidants may play a protective role. PMID- 2916205 TI - [New therapeutic alternatives for patients with gallstones]. AB - Calculi in the bile ducts are usually removed by surgery or endoscopic papillotomy. When these methods are contraindicated or fail, new and non-surgical alternatives can now be used. Percutaneous transhepatic balloon dilatation of the papilla of Vater enables expulsion of stones in the bile duct. Large stones in the bile ducts can be reduced in size using extracorporeal shock waves or completely dissolved by instillations of Methyl-tertiary-butyl ether in the common bile duct. We report the cases of three patients who were treated successfully for stones in the bile duct using combinations of these techniques. PMID- 2916206 TI - [Statistic programs for personal computers]. PMID- 2916207 TI - [Evaluation of a self-care leaflet]. AB - A self care leaflet of 50 pages was distributed in Tingvoll, a municipality with 3,500 inhabitants. The leaflet gives advice about self treatment and prevention of common health problems, and guidelines for contacting the health services. In surveys conducted just before and 10 months after the distribution, we documented -- how the leaflet was accepted and used --changes in knowledge about the health problems mentioned in the leaflet. The leaflet was well accepted. It was characterized as easy to read and to use. 10 months after distribution to read and to use. 10 months after distribution 90% found it within five minutes. 63% used the leaflet when they had a health problem. 90% of those using the leaflet felt more sure that they acted correctly after consulting it, and 60% changed their mind about consulting a general practitioner. We consider the level of knowledge about health problems to be low. The evaluation showed increased knowledge in all groups, except for persons "responsible for caring for elderly relatives". The increase was most marked for "men" and for "persons with health education". PMID- 2916208 TI - [HIV testing of hospital patients]. PMID- 2916209 TI - [Medicine and the media]. PMID- 2916210 TI - [Clinical trials in Norway]. PMID- 2916211 TI - [Vascular injuries]. PMID- 2916212 TI - [Clinical trials reported to the Norwegian Drug Control Authority during the period 1982-1986]. AB - During the five-year period 1982-86, 1,087 clinical drug trials were notified to the Norwegian Medicines Control Authority. There was in this period a slight decline in the annual number of notifications, whereas the number of patients/volunteer subjects in clinical trials rose. During the five-year period, every fifth professionally active physician in Norway notified at least one clinical trial to the Authority. Less than 10% of the trials notified did not involve participation by manufacturers. The trials covered a large number of substances. Most trials concerned drugs in the cardiovascular (c) and central nervous system (N) therapeutic groups. The frequency of reports on completed trials is low, and there are signs that some obligatory notifications of clinical trials are not sent to the Authority. PMID- 2916213 TI - [Clinical trials of antineoplastic agents reported to the Norwegian Drug Control Authority during the period 1982-1986]. AB - We surveyed clinical trials of anti-tumour drugs notified to the Norwegian Medicines Control Authority during the period 1982 to 1986. 91 trials of anti tumour drugs were notified during the period. A relatively large number of the trials were carried out without a control group, and a statistical rationale for the number of patients was lacking in almost 60% of the protocols. In 40% of the notified trials the manufacturers were not involved. Records of written information to patients have improved, as has insurance of the patients. On the other hand, reports on ongoing and completed clinical trials are still too often neglected. PMID- 2916214 TI - [Arterial injuries]. AB - During the years 1963-87, 57 patients were treated for arterial injuries. Iatrogenic injuries are excluded. 60% were due to accidents and only 12% to interpersonal violence. Three patients died from the injuries, eight extremities required a primary amputation, eight patients got sequela related to orthopedic problems or ischemia, and 35 patients achieved complete restitution of function. 53% of the injuries were due to fractures, dislocations or contusions while 21% were caused by penetrating lesions. The most common lesion was an intimal rupture with dissection and thrombosis in an otherwise intact vessel (40%). The most frequently applied technique of reconstruction was longitudinal arteriotomy with thrombendarterectomy and patch plasty. Other arteries were repaired by direct suture, interposition of a suitable graft or by a bypass. Fasciotomies were based on liberal indications. A high degree of diagnostic alertness is necessary if irreparable ischemic damage is to be avoided. PMID- 2916215 TI - [Late sequelae after arterial injuries]. AB - Of 57 patients with arterial injuries, three died, eight had an amputation and 14 experienced various kinds of late sequelae. Four of the sequelae were due to inadequate primary surgical treatment: 1) A 16 year-old girl developed incapacitating claudicatio intermittens after a traffic accident causing serious contusions to the right leg. Angiography four years later showed occlusion of the popliteal artery, which was successfully reconstructed. 2) A 16 year-old boy had a femoral fracture with injuries to the femoral artery and vein. The vessels were reconstructed and circulation was restored, but fasciotomies were not performed. He developed a flexion contracture of the 1st toe which required resection of the proximal phalanx. This was interpreted as a Volkmanns contracture due to a compartment syndrome in the deep, posterior compartment of the leg. 3) A 18 year old man had a fracture of the leg. Angiography demonstrated a minimal leak from the posterior tibial artery, but this was not surgically explored. Six weeks later a pseudoaneurysm ruptured and produced a large hematoma. Circulation was restored by arteriotomy and a patch plasty. 4) A 24 year-old man was hit in the groin by a 22 caliber rifleshot. An arteriovenous fistula was diagnosed but not surgically treated. Six years later he experienced cardiac failure and venous insufficiency. The fistula was closed, whereafter the symptoms disappeared. Blood flow in the fistula was 7,500 ml/min and the pressure in the distal femoral vein 37 mm Hg. These complications can be avoided by proper investigation and surgery at the time of initial treatment. PMID- 2916216 TI - [Respiratory changes in deep diving]. AB - Deep diving refers to saturation diving to a depth of more than 180 m (1.9 MPa ambient pressure). In the 1990s diving to 400 m may be necessary on the Norwegian continental shelf. The safety margins are narrow and at such depths the respiratory system is subject to great strain. Respiratory resistance increases and the dynamic lung volumes are reduced as the pressure increases due to enhanced gas density. Helium is used together with oxygen as breathing gas and the lower density partly normalises the dynamic lung volumes. The respiratory system imposes clear limitations on the intensity and duration of physical work during deep diving. We lack systematic studies of lung mechanics, gas exchange and respiratory regulation in the different phases of deep dives. Demonstration of possible chronic occupational respiratory diseases connected to diving is dependent on follow-up over a long time. PMID- 2916217 TI - [Nosocomial infections with resistant Enterobacter cloacae. Effects on the disease and the treatment]. AB - We describe five patients with serious nosocomial infection caused by resistant Enterobacter cloacae. Four of the patients underwent cardiovascular operations and were infected with an identical, multiple beta-lactam resistant E cloacae strain. The fifth patient was admitted with several wounds and skin-ulcers containing both resistant and sensitive E cloacae of other types. The resistant strain caused septicemia in four patients; three developed multiorgan failure and one died. The most probable causes of these infections were an abundant and constant reservoir of E cloacae in a sink at the operating unit, periodical breakdown of barriere routines, and heavy use of cephalosporins. PMID- 2916218 TI - [Testicular cancer. A challenge to the health services taking care of young males]. AB - About 130 Norwegian men (15-45 years old) develop testicular cancer each year. Men with a history of undescended testes, atrophic testes and/or fertility problems probably represent a high risk group. Typical symptoms are tumour, harder consistency and discomfort in the testes, low back pain and gynecomastia. Testicular ultrasonography often helps to establish the correct diagnosis. Seminoma is separated from non-seminoma histologically. Adjuvant radiotherapy to the retroperitoneal lymph nodes is the most frequent treatment in seminoma patients with early disease and is combined with chemotherapy in patients with advanced disease. Chemotherapy and surgery are the main therapeutic modalities in non-seminoma patients. In clinical trials a "wait and see" policy is applicable in selected patients with non-seminoma without metastases, provided that frequent follow-up examinations are feasible. Gastrointestinal side effects, alopecia, peripheral neuropathy and azoospermia are the most frequent acute and reversible side effects of treatment of testicular cancer. Post-treatment paternity can be achieved by at least half of the patients who wish to father a child after treatment. The 5-years' survival rate for young patients with testicular cancer is 95%. Young men should perform testicular self-examination regularly. Medical officers in the Armed Forces and doctors at schools and universities and in occupational health should be aware of testicular cancer in young adults with suspicious clinical findings. PMID- 2916219 TI - [Respiratory tract diseases caused by the environment]. AB - Large variations in the development of chronic airway disturbances in the population have been uncovered, together with possible increased risk of such disturbances. There seems to be a connection to exposure to pollutants at work and in home environment. The interconnection and interaction between irritants, allergens, infectious agents and other biologically active substances may have a decisive impact on the risk an individual runs of developing chronic suffering in the upper and lower respiratory tract. Injuries in mucous membranes and airways, connected with the development of unspecific hyperreactivity may play a central role in the development of allergic and nonallergic airway disturbances and diseases. These findings may have a decisive influence on the choice of prophylaxis and therapy. PMID- 2916220 TI - [Occupational diseases among personnel at a radiology department]. AB - Little attention has hitherto been paid to health injuries to personnel in X-ray departments after exposure to photochemicals. 24 out of 30 employees at the X-ray department in Molde were shown to have health problems related to their work, including symptoms relating to the eyes, the upper and lower respiratory tract, and headache and lassitude. Analysis of the work environment showed constant extensive exposure of the employees to chemicals over a long period. After improvements to the environment the health problems were reduced appreciably, but not nullified. Some personnel had acquired permanent impairments. Bronchial hyperreactivity was discovered in 19 of the personnel, 13 of whom had subjective symptoms of obstruction and asthma but no manifestation of allergy. The author discussed the relation between the work environment and the impaired health and gives advice on how to avoid similar problems in the future. PMID- 2916221 TI - [Candida albicans--is it causing a new national disease?]. AB - A hypothesis concerning a chronic candida hypersensitivity syndrome caused by the presence of Candida albicans in the gut was put forward in the USA a decade ago. Lately this theory has gained much publicity in Norway through articles in the press and programs on the national radio and television. The purpose of this article is to give a presentation and critical evaluation of this syndrome. It is concluded that the theory of a chronic Candida hypersensitivity syndrome is speculative and devoid of experimental support. PMID- 2916222 TI - [Photochemicals and their effects on health]. AB - The discovery of health hazards related to work in X-ray departments and photographic laboratories is a strong incentive for extensive analysis of the interrelationship between photochemicals and their impacts on health. The chemicals which pollute the environment in such premises may cause symptoms related to the skin, mucous membranes, eyes and airways. Teratogenic, mutagenic and neurotoxic effects cannot be excluded. PMID- 2916223 TI - [Military insurance. Military insurance regulations and the handling of diseases/injuries among draftees]. AB - This article discusses civilian and military insurance regulations, including social support in case of illness or injury during compulsory military service. The procedure is exemplified by the treatment of conscripts who are diagnosed as having cancer testis while doing their compulsory service. It is essential that civilian medical practitioners are familiar with this procedure, so that they can advise any conscripts who consult them. PMID- 2916224 TI - [Complaints from cancer patients. Complaints and ways of complaining]. PMID- 2916225 TI - [Research and prejudice]. PMID- 2916226 TI - [Lecture nights for family members of schizophrenics. Psychiatry with a humane approach]. PMID- 2916227 TI - Joint session of the German Society for Vascular Surgery and the German Society for Thoracic and Cardiovascular Surgery. (18th annual meeting). February 23 February 25, 1989, Munich. Abstracts. PMID- 2916228 TI - 4th International Conference on Human Leucocyte Differentiation Antigens. Vienna, February 21-25, 1989. Abstracts. PMID- 2916229 TI - Species-specific hemolysis of erythrocytes by T-2 toxin. AB - The tricothecene mycotoxin, T-2 toxin interacts differently with mammalian erythrocytes. Pig, man, rabbit, guinea pig, horse, dog, rat, and mouse erythrocytes are all lysed to a varying degree by T-2 toxin. But cow, sheep, goat, buffalo, and deer erythrocytes are all resistant to hemolysis by T-2 toxin. Since erythrocytes from ruminant animals contain little or no phosphatidylcholine, perhaps the presence of phosphatidylcholine in the membrane is required for the hemolytic action of T-2 toxin. Sheep erythrocytes were used to encapsulate T-2 toxin further confirming the resistance of erythrocytes from animals with ruminant physiology to T-2 toxin lysis. PMID- 2916230 TI - Prenatal or postnatal exposure to bis(tri-n-butyltin)oxide in the rat: postnatal evaluation of teratology and behavior. AB - The results of a series of screening tests to determine the potential teratogenicity and neurotoxicity of developmental exposure to TBTO in rats are presented in this paper. For prenatal exposure, pregnant Long Evans rats were intubated with 0-16 mg/kg/day bis(tri-n-butyltin)oxide TBTO from Days 6 to 20 of gestation (GD 6-20). For postnatal exposure, rat pups were intubated with 0-60 mg/kg TBTO on Postnatal Day 5 (PND 5). Following prenatal exposure, dams were allowed to litter and pups were evaluated using a postnatal teratology screen. Postnatal evaluation for both exposures included motor activity (PND 13-64), the acoustic startle response (PND 22-78), growth, and brain weight. The maximally tolerated dose (MTD) in pregnant rats was 5 mg/kg/day, which is one-third the MTD in nonpregnant rats. There were decreased numbers of live births, and decreased growth and viability at dosages greater than or equal to 10 mg/kg/day. Cleft palate was found in 3% of the 12 mg/kg/day group. There was mortality following postnatal exposure to 60 mg/kg and all prenatal dosages greater than or equal to 10 mg/kg/day. Preweaning body weight was significantly decreased for all postnatal dosages, and all prenatal dosages greater than 2.5 mg/kg/day. Body weight reductions persisted to the postweaning period only in the high dose groups (10 mg/kg/day and 60 mg/kg). Behavioral evaluation demonstrated transient alterations in motor activity development (prenatal exposure only) and the acoustic startle response (postnatal exposure only). Persistent behavioral effects were observed only at dosages that produced overt maternal toxicity and/or postnatal mortality. The demonstration of the teratogenic and neurotoxic potential of TBTO in rats is confounded by associated maternal toxicity and/or pup mortality. PMID- 2916231 TI - Embryo-maternal distribution of basic compounds in the CD-1 mouse: doxylamine and nicotine. AB - The intracellular pH of the early postimplantation rodent embryo (pHi) is alkaline with respect to the corresponding plasma of the pregnant dam. This transplacental pH gradient is of considerable importance in the accumulation of teratogenic weak acids by the embryo. The importance of pH in the partitioning of basic drugs across the early mammalian placenta has not been investigated. Theoretically, the maternal plasma should retain a higher concentration of basic drugs than the embryo due to a greater degree of drug ionization in the more acidic plasma. To explore the significance of pH partitioning upon the transplacental distribution of basic compounds, two bases, doxylamine and nicotine, were administered to pregnant CD-1 mice during early organogenesis. The maternal plasma and embryonic concentrations of the bases were measured and the resulting embryo/maternal plasma (E/P) ratio was calculated and compared to the ratio predicted by the Henderson-Hasselbalch equation. Following ip injection of nicotine on Day 9 of gestation, the E/P ratio was significantly greater than the predicted ratio 10 min after injection and continued to rise for 3 hr. For doxylamine succinate administered by oral gavage on Day 9 or 10, the E/P ratio was also significantly greater than the ratio predicted from the pH gradient. Our results indicate that the partitioning of these basic compounds between the maternal plasma and the early postimplantation rodent embryo is not a consequence of the pH gradient between the two compartments alone. PMID- 2916233 TI - Cardiac mitochondrial calcium content during fatal doxorubicin toxicity. AB - The purpose of this study was to determine whether abnormalities of mitochondrial divalent cation metabolism are early, causative events in doxorubicin (DXR, Adriamycin) cardiotoxicity. We used electron probe microanalysis (EPMA) to examine the calcium (Ca) and magensium (Mg) content of in situ mitochondria in cryosections of rat hearts, rapidly frozen at 6 hr and 1, 3, and 5 days after a single iv injection of 20 mg/kg DXR. This dose produced 100% mortality in 7 days, with a mean survival of 5.8 days. Mean control mitochondrial Ca and Mg was 0.7 and 28 mmol/kg dry wt, respectively (+/- SEM), and did not change in the DXR injected animals, even in severely symptomatic rats 5 days after DXR. This suggests that an alteration in mitochondrial divalent cation metabolism is unlikely to be a primary event in the pathogenesis of DXR-induced cardiotoxicity, and that the mitochondrial Ca accumulation demonstrated in previous studies represents a secondary event in cells damaged by another mechanism. PMID- 2916232 TI - Comparative dermal absorption of 2,3,7,8-tetrachlorodibenzo-p-dioxin and three polychlorinated dibenzofurans. AB - Polychlorinated dibenzodioxins (PCDDs) and dibenzofurans (PCDFs) are toxic environmental contaminants which have the potential to accumulate in human tissues. In order to examine the potential for systemic exposure following dermal exposure, the absorption, distribution, and elimination of 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD), 2,3,7,8-tetrachlorodibenzofuran (TCDF), 1,2,3,7,8-pentachlorodibenzofuran (1PeCDF), and 2,3,4,7,8-pentachlorodibenzofuran (4PeCDF) were evaluated in male F344 rats. TCDD (0.00015, 0.001, 0.01, 0.1, 0.5, and 1.0 mumol/kg) and the three PCDFs (0.1, 0.5, and 1.0 mumol/kg) were applied to a preclipped region on the back of the rat and covered with a perforated cap. The rats were held in individual metabolism cages for 3 days. In animals administered 0.1 mumol/kg, the absorption of TCDF was greater than that of 4PeCDF, 1PeCDF, and TCDD. Relative absorption (percentage of administered dose) declined with increasing dose while the absolute absorption (microgram/kg) increased nonlinearly with dose. Absorption of TCDF at 0.1 mumol/kg was 48% of the administered dose which was significantly greater than that of the other compounds. At this dose, absorption of 4PeCDF was greater than that of TCDD. Absorption at the higher doses was similar for all four compounds. Maximum relative absorption of TCDD (approximately 40% of the administered dose) was obtained at 0.001 and 0.00015 mumol/kg. Major tissue depots for these four chemicals included liver, adipose, skin, and muscle tissue; however, the liver:fat ratio for 4PeCDF was approximately fourfold higher than that for the other three compounds. When normalized to 100% of dose absorbed, the distribution of 4PeCDF-derived radioactivity in liver and adipose tissue was similar to that previously observed after oral and iv administration. In animals administered 0.1 mumol TCDF or 1PeCDF/kg, 56 and 32% of the respective absorbed dose was excreted as polar metabolites within 3 days. Very little of the absorbed dose of either TCDD (approximately 10%) or 4PeCDF (approximately 2%) was eliminated. Results indicate that the dermal absorption of these compounds is incomplete and that systemic toxicity following acute dermal exposure to levels found in the environment is unlikely. PMID- 2916234 TI - Hematopoietic effects in mice exposed to arsine gas. AB - Arsine gas is a potent hemolytic agent. Concern about semiconductor workers prompted an in-depth study of arsine at the National Institute of Environmental Health Sciences to determine the hematopoietic effects of prolonged exposure to this gas. Female B6C3F1 mice were exposed by inhalation to 0, 0.5, 2.5, and 5 ppm arsine, 6 hr/day for 14 days. Body weights of exposed mice were comparable to those of controls, but a marked, concentration-related splenomegaly was observed. Higher level arsine exposure produced statistically significant decreases in red blood cells, hematocrit and hemoglobin, with increases in white blood cell counts and mean corpuscular volume of red blood cells. Erythropoiesis as measured by quantitation of erythroid precursors in culture revealed a marrow reduction of colony-forming unit erythroids/femur cells for all treated groups on Day 3 postexposure and only at the 5 ppm dose group on 24 days postexposure, while splenic erythropoiesis increased at higher concentrations of arsine. There was no alteration in bone marrow cellularity and a less significant effect on granulocyte-macrophage progenitors. A 12-week study of arsine at 0, 0.025, 0.5, and 2.5 ppm (6 hr/day) by inhalation showed similar effects on hematopoiesis in mice. In conclusion, arsine exposure at low concentrations produces a stress on the hematopoietic system characterized by hemolysis, which persists for a prolonged period following exposure. PMID- 2916236 TI - Correlation between morphologic and functional changes induced by xenobiotics: is every induced change a sign of toxicity? PMID- 2916235 TI - Studies on the etiology of trace metal-induced porphyria: effects of porphyrinogenic metals on coproporphyrinogen oxidase in rat liver and kidney. AB - Studies were conducted on the etiology of trace metal-induced porphyria in rats, with particular emphasis on the action of metals on hepatic and renal coproporphyrinogen oxidase. Prolonged exposure of rats to methyl mercury hydroxide or sodium arsenate at subtoxic dose levels in drinking water resulted in a progressive coproporphyrinuria, reaching highest rates of coproporphyrin excretion 5 weeks after initiation of exposure. The development of coproporphyrinuria was accompanied by substantial metal accumulation in the kidney and a significant decrease in renal, but not hepatic, coproporphyrinogen oxidase activity. During prolonged exposure to either metal, the rates of coproporphyrin excretion and metal accumulation by the kidney continued to increase for 2 to 3 weeks following maximal inhibition of renal coproporphyrinogen oxidase. Acute treatment studies and studies in vitro support the conclusion that the kidney is the principal source of excess urinary coproporphyrin during metal exposure. These observations demonstrate that metal induced coproporphyrinuria is predominantly of renal etiology and that impairment of renal coproporphyrinogen oxidase is a principal cause of this effect. PMID- 2916237 TI - Differential induction and regulation of peroxisomal enzymes: predictive value of peroxisome proliferation in identifying certain nonmutagenic carcinogens. AB - Hypolipidemic drugs and certain plasticizers markedly increase the number of peroxisomes in liver parenchymal cells. Continued exposure to peroxisome proliferators has been shown to produce essentially similar pleiotropic responses leading eventually to the development of liver tumors in rats and mice. These agents are not mutagenic in short-term test systems and do not appear to interact with or damage DNA. Accordingly, the events leading to or associated with the induction of peroxisome proliferation have been postulated to play a role in the development of liver tumors. Recent evidence indicates that persistent peroxisome proliferation leads to the formation of 8-hydroxyguanosine in rat liver DNA, which supports the role for oxidative stress. The mRNAs of the three peroxisomal beta-oxidation genes are induced over 20-fold in the livers of rats treated with nafenopin, Wy-14643, BR-931, and other structurally diverse peroxisome proliferators. This increase in beta-oxidation mRNAs is evident within 30 min to 1 hr and was maximal 8 to 16 hr after the administration of a single dose of these agents by gavage. The peroxisomal catalase and urate oxidase mRNAs increase about 2-fold in the livers of rats treated chronically with peroxisome proliferators. These results indicate that peroxisome proliferators differentially regulate different peroxisomal enzymes. The tissue specificity of peroxisomal beta-oxidation gene regulation by xenobiotics supports the contention that the development of liver tumors following exposure to peroxisome proliferators correlates well with the inducibility of peroxisome proliferation and the beta-oxidation genes. Although these agents are known to exert mitogenic response in liver, it is unlikely that stimulation of DNA synthesis alone is responsible for tumor development. Cell proliferation may, however, play a secondary role. The morphological phenomenon of peroxisome proliferation should serve as a simple, sensitive, and valuable biological indicator for the identification of nongenotoxic or nonmutagenic chemicals that may be carcinogenic. An understanding of the cellular and molecular basis of peroxisome proliferation is a prerequisite for the evaluation of toxicological implications of this phenomenon. PMID- 2916238 TI - The reversible carbamate, (-)physostigmine, reduces the size of synaptic end plate lesions induced by sarin, an irreversible organophosphate. AB - Pretreatment of rats with atropine and the reversible esterase inhibitor physostigmine [-)PHY), prior to injection of a lethal dose of the irreversible organophosphate sarin (0.13 mg/kg), protects 100% of the animals from lethality. We have used quantitative light and qualitative electron microscopy to show that damage to the end plate region of voluntary muscles is also strikingly limited by the same pretreatment. Drug effects on soleus motor end plates detectable 1 hr after treatment were (1) a single sublethal dose of sarin (0.08 mg/kg) produced large, blistered, and severely disrupted subjucntional regions. Damage extended from the end plate, in the form of myofiber necrosis and subsequent phagocytosis; (2) (-)PHY (0.1 mg/kg) itself had a selective effect in inducing irregularities of the subjunctional sarcomere band without any gross vacuolization; (3) the morphometric analysis done with light microscopy indicated that the combination of atropine (0.5 mg/kg) and (-)PHY (0.1 mg/kg) prior to a lethal dose of sarin (0.13 mg/kg) offered 86% reduction in the average area of the lesions, relative to the dimensions of damage induced by atropine/sarin alone. In most lesions induced by (-)PHY, recognizable changes were markedly less severe in degree and extent than those seen in sarin myopathy; there were few instances of extensive muscle damage and myofiber necrosis. The relationship of the (-)PHY dose to the level of protection against sarin suggested that (-)PHY pretreatment almost completely prevents the characteristic sarin-induced myopathy and, instead, imposes the characteristic PHY-induced subjunctional swelling. In all three experimental groups examined, the myopathic changes located extrajuctionally were reversible. The mechanism by which (-)PHY acts as a protective agent is discussed. PMID- 2916239 TI - Persistent effects of neonatal toluene exposure on regional brain catecholamine levels and turnover in the adult male rat. AB - Effects of neonatal toluene exposure (80 ppm, day 1-7, 6 h/day) have been studied on regional brain catecholamine levels and utilization, and on serum levels of hypophyseal and adrenocortical hormones in the adult male rat. Catecholamine levels were measured by quantitative histofluorimetry in the forebrain and hypothalamus and by high pressure liquid chromatography with electrochemical detection in the substantia nigra. Catecholamine utilization was evaluated from the decrease in catecholamines seen after tyrosine hydroxylase inhibition using alpha-methyl-p-tyrosine methyl ester hydrochloride (alpha MT, 250 mg/kg, i.p., 2 h). Serum levels of thyroid stimulating hormone, corticosterone, aldosterone, prolactin and luteinizing hormone were measured by radioimmunoassays. Neonatal toluene exposure produced a reduction of dopamine levels and utilization selectively in the olfactory tubercle and substantia nigra of the adult rat. Furthermore, neonatal toluene exposure produced a significant reduction in the noradrenaline levels and utilization in the substantia nigra and an increase of noradrenaline utilization selectively in the subependymal layer of the median eminence and of the magnocellular part of the paraventricular hypothalamic nucleus. The serum hormone levels were not significantly influenced by neonatal toluene exposure as evaluated in adulthood. However, the alpha MT induced increase in serum prolactin levels was reduced following neonatal exposure to toluene. Neonatal toluene treatment was also found to alter the responses of the catecholamine neurons to subacute toluene exposure in adulthood. In some of the dopamine nerve terminal systems of the forebrain and in the dopamine cell body containing area of the substantia nigra neonatal toluene exposure appears to have made the dopamine neurons insensitive to adult subacute toluene exposure. In the hypothalamic noradrenaline nerve terminal systems, there were even reversed responses to subacute toluene exposure. The present results indicate that neonatal toluene exposure in doses at the threshold limit value produces persistent changes in dopamine and noradrenaline neurons of the forebrain, hypothalamus and substantia nigra in the presence of a relatively intact neuroendocrine system. In addition, neonatal toluene exposure appears to diminish or even counteract the responses to subacute toluene treatment in adulthood. PMID- 2916240 TI - Detection of reactive metabolites in vitro. AB - The ability of 27 compounds to mediate depletion of glutathione (GSH) in a fortified liver microsome incubation via production of reactive metabolites generated by microsomal mono-oxygenase (MMO) metabolism has been studied. The majority of compounds tested of this type were positive in this assay, with the exception of iproniazid and naphthalene. Thioacetamide, the reactive metabolite of which binds via lysine residues, was negative. Acrolein and hexachlorobutadiene produced depletion in the absence of prior activation, as did menadione but for which enzyme induction increased the magnitude of depletion. Allyl alcohol produced MMO-mediated depletion of GSH. Some depletion of GSH occurred in the presence of common substrates of the MMO system. It is suggested that this depletion assay may be a valid test for detection of reactive metabolites generated by MMO metabolism. PMID- 2916241 TI - Epiphyseal lesions of the femur and tibia in rats following oral chronic administration of zinc dimethyldithiocarbamate (ziram). AB - A 24-month chronic feeding toxicity study with zinc dimethyldithiocarbamate (ziram) was performed on Fischer 344 rats of both sexes (80 animals/sex per group) at dietary levels of 0, 20, 200, or 2000 ppm. Eight animals of either sex from each group were sacrificed after 26, 52 and 78 weeks, and all surviving animals were killed after 104 weeks. Epiphyseal abnormalities in the long bones of the hind legs were observed in both sexes at 2000 ppm. Clinically, 3 male rats showed partial paralysis of the hind legs. At necropsy, marked curvature of the proximal end of the crus which could cause a restricted extension of the tibio femoral joint was seen in 11 of 34 males killed at terminal sacrifice. While females had neither clinical signs nor gross abnormalities during the study, histopathological examination revealed retarded epiphyseal closure of the proximal end of the tibia in both sexes. Females also showed the epiphyseal lesion at the distal end of the femur. In severely affected rats marked proliferation of epiphyseal cartilaginous tissue was also noted together with the irregular arrangement of chondrocytes. These changes were evident only in aged animals. The incidence of the lesions in all males and females examined in this group was 22/77 (29%) and 13/73 (18%), respectively. The occurrence of the lesions appeared to be caused by impaired regulation of epiphyseal closure which might be related to the treatment with ziram. PMID- 2916242 TI - Uptake of 63Ni2+ in the central and peripheral nervous system of mice after oral administration: effects of treatments with halogenated 8-hydroxyquinolines. AB - Oral administration of 63Ni2+ to mice resulted in higher levels of the metal in the sciatic nerves, the trigeminal ganglia, spinal nerve roots and the spinal cord than in the cerebellum and the frontal cortex. In the sciatic nerves, the trigeminal ganglia and the spinal nerve roots a high vascular permeability may explain the preferential uptake of the 63Ni2+. The higher accumulation of the 63Ni2+ in the spinal cord than in the examined structures of the brain may be related to a diffusion from the cerebrospinal fluid. Administrations of halogenated 8-hydroxyquinolines [5,7-diiodo-8-hydroxyquinoline (diI-HQ), 5,7 dibromo-8-hydroxyquinoline (diBr-HQ), 5,7-dichloro-8-hydroxyquinoline (diCl-HQ) or 5-chloro-7-iodo-8-hydroxyquinoline (Cl-I-HQ)] together with the 63Ni2+ resulted in increased levels of the metal both in neural and extraneural tissues in comparison with mice given the 63Ni2+ alone. In most instances the tissue levels of 63Ni2+ were 2-4 times higher in the animals treated with the halogenated 8-hydroxyquinolines than in the controls. Determinations of chloroform/water partition coefficients showed that lipophilic chelates are formed between each of these compounds and the nickel. Our results are probably explained by a facilitated passage of the complexed metal over the walls of the stomach and the intestine. The halogenated 8-hydroxyquinolines are linked with the SMON-syndrome, a disease which occurred primarily in Japan. The possibility that this syndrome may be causally connected with a concomitant intake of these drugs and metals is discussed. PMID- 2916243 TI - Long-term feeding study of N,N'-diphenyl-p-phenylenediamine in F344 rats. AB - Groups of 50 F344 rats of each sex were fed a diet containing 0.5 or 2% of N,N' diphenyl-p-phenylenediamine (DPPD) for 104 weeks and were killed 8 weeks after the cessation of DPPD administration. DPPD-treated rats of both sexes showed a dose-dependent reduction in body weight gain, but no lower survival rate, when compared with untreated control rats. Blood and urine analysis showed no remarkable changes due to the treatment. Calcium deposition in the kidney of males was the only significant histological change relating to the treatment. Tumors were found in many organs of all groups, but a significant increase of tumor induction in DPPD-treated groups was not observed. PMID- 2916244 TI - The biochemical and pathological changes produced by the intratracheal instillation of certain components of zinc-hexachloroethane smoke. AB - Zinc chloride which is formed by igniting a mixture of zinc oxide and hexachloroethane in the production of white smokes has been shown to produce oedema when given to rats as a single instillation. The oedematous reaction, as assessed by histopathology and measurements of alveolar surface protein in lavage fluid, is variable, dose-dependent, and maximal at 3 days but at sub-lethal doses it regresses after 7 days. The parent compound, zinc oxide, does not produce these effects. In some animals there is evidence of a fibrogenic response at 7 days post-exposure although it is currently unknown whether or not this effect is progressive. PMID- 2916245 TI - Validation of a morphometric analysis procedure using indomethacin-induced alterations in cultured hepatocytes. AB - Morphometric analysis was used to quantitate indomethacin-induced morphological changes in primary cultures of neonatal rat hepatocytes by comparison with standard assessments of functional integrity (i.e. enzyme release, urea levels, and dye exclusion). For this procedural validation, indomethacin concentrations were selected to correspond to the therapeutic plasma levels of rheumatoid arthritic or systemic lupus erythematosus patients having liver cell injury secondary to prolonged, high-dose administration of this nonsteroidal antiinflammatory agent. Primary cultures of neonatal rat hepatocytes were exposed for 12 h to 0, 100, 500 or 1000 microM indomethacin and subjected to a double blind morphometric analysis procedure modified for use on cultured cells. This procedure systematically converted two-dimensional morphologic information into three-dimensional numerical data for statistical analysis. These optical measurements provided an accurate analysis following 4 h of measurements. When the concentration of indomethacin was increased from 0 to 1000 microM, the relative volume percent of Type I cells decreased. Therefore these cells, which were indistinguishable from healthy, untreated control cells, become less numerous as toxicant level increased. In contrast, the relative volume percent values of other progressively more damaged cell types (i.e. Types II, III, and IV cells) increased with elevation of indomethacin levels. Morphometric assessments paralleled functional assessments of indomethacin-induced cytotoxicity (r2: 0.88 0.99). Therefore, the present study validated this morphometric analysis procedure using a rigorous cellular exposure which caused substantial cell injury and subsequent lifting of 23% cells from the substrate. Combined with previous validation studies involving cadmium, erythromycin and benoxaprofen, the present study showed that morphometric analysis is a rapid, accurate method for the measurement of cell injury in cultured parenchymal hepatocytes. PMID- 2916246 TI - Tris acetylacetonate aluminium(III) induces osmotic fragility and acanthocyte formation in suspended erythrocytes. AB - Tris acetylacetonate aluminium(III) (Al(acac)3), dissolved in water, is effective in producing osmotic fragility in suspended erythrocytes in the concentration range of 0.034-0.34 mmol/l. Water solutions of Tris maltolate aluminium(III) (Al(malt)3) and aluminium lactate (Al(lac)3) are also effective but the dose response behavior is less pronounced. Moreover, only Al(acac)3 induces a prominent generation of acanthocytes. The stronger effects of Al(acac)3 on membrane stability are attributed to the greater solubility of this complex in the cell membrane. PMID- 2916247 TI - Cadmium and metallothionein levels in the liver of humans exposed to environmental cadmium in Upper Silesia, Poland. AB - The area of Upper Silesia is the most industrialized region in Poland. The concentrations of cadmium (Cd), zinc (Zn), copper (Cu) and metallothionein (MT) in autopsy samples (n = 29) of liver from the inhabitants of that area were determined. The metal levels varied in the ranges of 0.5-11.9 micrograms Cd/g, 45.3-221.6 micrograms Zn/g, 1.4-10.3 micrograms Cu/g. The concentration of MT determined by the Hg-method was high: 0.38-2.86 mumol Hg/g. A positive linear relationship was observed between Zn and MT levels. PMID- 2916248 TI - Metallothionein-I accumulation in the rat lung following a single paraquat administration. AB - The ability of paraquat (PQ), a free radical inducible chemical, to increase metallothionein-I (MT-I) content in the tissues was determined using radioimmunoassay. A single dose of PQ into the rat caused a sevenfold increase in pulmonary MT-I concentration on day 1 and its concentration returned to the control level by day 5. Paraquat-induced increase in MT-I was not observed in the kidney, but was seen in the liver. The data show the difference in accumulation of MT-I in liver, kidney and lung after intraperitoneal injection of a high dose of PQ. PMID- 2916249 TI - Toxic responses in F344 rats and B6C3F1 mice given roxarsone in their diets for up to 13 weeks. AB - Thirteen-week toxicity studies were conducted in groups of 10 F344 rats and B6C3F1 mice of each sex fed roxarsone at 0, 50, 100, 200, 400, or 800 ppm in the diet. Arsenic levels in blood, urine, kidneys, and liver of rats were measured in additional animals of each sex dosed with 100 or 400 ppm roxarsone. Compound related mortality occurred in both sexes of rats at 800 ppm and mice at 800 and 400 ppm. Significant body weight gain depression occurred in both sexes of rats at 200, 400, and 800 ppm and mice at 800 ppm. Clinical signs of toxicity (trembling, ataxia, and pale skin) were seen primarily in rats and mice at 800 ppm. Lesions associated with roxarsone administration were noted only in the kidney of rats and were characterized by tubular necrosis and mineralization at the corticomedullary junction. Arsenic levels in urine, blood, liver, and kidneys increased over time and were directly proportional to the level of roxarsone in feed. These levels were greater than 6 times higher in rats than in mice and were about 2 time higher in males than in females. The no-observable-effect level for roxarsone toxicity was estimated at 100 ppm for rats and 200 ppm for mice. No hematology or clinical chemistry effects were found in rats or mice of either sex. PMID- 2916250 TI - Study on dermal toxicity and urinary metabolites of the new insect repellent N,N diethylphenylacetamide in rabbits. AB - Dermal toxicity of the new multi-insect repellent N,N-diethylphenylacetamide (DEPA) was studied in female rabbits. LD50 of DEPA was estimated to be 3505 mg/kg b.w. On daily topical application for 21 d at a dose of 50 mg/kg b.w., dermal irritancy score and blood chemistry changes indicated that the compound is non irritant and non-toxic. N-Ethylphenylacetamide and conjugated phenylacetic acid were identified as the urinary metabolites of DEPA by gas-liquid chromatography. PMID- 2916251 TI - Characterization and development of metallothionein in fetal forelimbs, brain and liver from the mouse. AB - The presence of the low molecular weight protein metallothionein (MT) has been investigated in fetal forelimbs, brain and liver from the mouse with the aim of using the protein as a biochemical marker for the early recognition of potential teratogenic agents in the future. Forelimbs, brain and liver were taken from mouse fetuses at ages ranging from 12 to 18 d. Each type of organ was homogenized and centrifuged at 9000 x g. The analysis of MT in the supernatants (S9) with the Cd-heme saturation method detected in all three cases the presence of a low molecular weight, Cd-binding protein whose concentration increased with the age of the fetus. Analysis of the S9 fractions using gel- and anion exchange chromatography and polyacrylamide gel electrophoresis demonstrated the existence of a protein analogue to the hepatic MT in forelimbs and brain. PMID- 2916252 TI - [Treatment methods of keloid and hypertrophic scar formation]. AB - Hypertrophic scar and keloid are diagnoses based on clinical symptoms. Hypertrophic scar is an unacceptably enlarged scar, within the boundaries of the original wound; whereas keloid is an unacceptably enlarged scar infiltrating the surrounding tissue. Hypertrophic scar and keloid belong to the same category of diseases, characterized by increased collagen development. The treatments employed are compression, excision, corticosteroid injections and irradiation. New medical treatments affecting the collagen metabolism such as colchicin, beta amino-proprionitrite (BAPN), D-penicillamine, cytostatics and prostaglandin inhibitors have been introduced with promising results and fewer side effects. PMID- 2916253 TI - [Parietal cell vagotomy and dilatation in duodenal ulcer complicated by pyloric stenosis]. AB - In a follow-up study of 32 patients with duodenal ulcer complicated by pyloric stenosis treated by highly selective vagotomy and dilatation of the stricture, we found an ulcer recurrence rate of 19% and a restenosis rate of 7.6% after a minimum of six years of observation. It is concluded, that dilatation can be used as an alternative to former surgical procedures in the treatment of pyloric stenosis and that highly selective vagotomy is still justified in the treatment of some cases of duodenal ulcer. PMID- 2916254 TI - [Diagnosis and treatment in general practice. Referral courses over a period of 1 year]. AB - This study examined episodes of medical care in five practices, representing a number of municipalities in The Copenhagen County. For comparison of results, data from a similar survey from a 55 practices' study by Hollnagel et al were also used. In these two surveys all encounters were recorded, over period of one year and three months, respectively, each time a health problem or condition was presented to the general practitioner following a personal, telephone or written contact between the patient, or other person representing the patient, and physician. The study population analyzed here consists of 189 and 2,293 adults respectively, who were all registered as group 1 members of the Danish National Health Care system. The date and nature of each contact were registered, including information of the date of any previous contact concerning the same health problem, so that the contacts could be chronicled into episodes of medical care. In addition, detailed data concerning encounter form, reason for encounter, patient's expressed whished to obtain specific services, general practitioners treatment including referrals, and diagnosis were recorded. Compared with the study covering a period of three months, the data covering a period of one year include episodes which represent a larger fraction of the study population in all age groups, 85-95% compared with 55-68%. Similarly a greater number of contacts in the episodes with a total of more than one contact are recorded over a period of one year especially concerning the episodes in the age group 45-64 years of age and the group over 65 years. PMID- 2916255 TI - [Acromioclavicular dislocation. Conservative or surgical treatment?]. AB - The anatomy of the acromioclavicular joint is described and the mechanism of trauma causing dislocation of the joint is presented. Acromioclavicular dislocation is subdivided according to Allman's classification and special lesions are described. The therapeutic principles are discussed on the basis of the literature. It is concluded that all grade 1 and grade 2 lesions may be treated symptomatically and conservatively with good results. Where grade 3 lesions are concerned, it is concluded that conservative therapy appears to provide better results than operation. The final functional results are the same and the period of convalescence is briefer with conservative therapy. In addition, complications of conservative therapy are less serious and are easy to treat with good results. PMID- 2916256 TI - [Acute poisoning with organic phosphates treated at an intensive care unit]. AB - During the period 1.1.1976 to 31.12.1985, 23 patients were treated in an intensive care unit following acute poisoning with organic phosphates. Sixteen of the cases of poisoning were intentional and were part of attempted suicide. Eight were accidental. The severe cases of poisoning were all attempted suicides. Nineteen of the cases of poisoning occurred during the months from April to August during which these sprays are employed. The average age was 41 years ant the sex ratio men: women was 3:0. Respirator treatment was necessary in six patients. Sixteen patients were treated with a bolus injection of atropine and/or continuous infusion and six of these patients received antidote treatment with obidoxim, simultaneously. It is concluded that the majority of cases of poisoning are with suicidal intent and employ preparations which are freely obtainable and that only very few cases of poisoning occur in professional persons in connection with their employment. Treatment of cases of acute poisoning with organic phosphates is both specific and symptomatic. A therapeutic programme is established which aims primarily at ensuring free respiration, prevention of further absorption of poison, specific antidote therapy with atropine and obidoxim and symptomatic therapy. PMID- 2916257 TI - [Forensic examination in cases of rape and attempted rape reported to the police. A study of a new procedure used in the municipality of Copenhagen]. AB - Increasing recognition of the late psychological sequelae of rape has resulted in alteration in the practice of medico-legal investigation in the Municipality of Copenhagen with the offer of psychological treatment free of charge. During a period of two years, 100 women were examined and 20% of these accepted psychological treatment. The percentage of women seeking psychological treatment was greatest among those who were examined in the new premises attached to the psychiatric clinic of the University Hospital. These premises satisfy a number of needs but are not optimal. A recent committee publication proposes a special clinic for victims of sexual assaults not only the women who have reported the case to the police but also those who have not reported it. A department such as this must be considered to be the optimal solution for solution of the requirements of victims of rape. The 20 women who received psychological treatment presented psychological symptoms of the same type and degree as described in other investigations, and these symptoms were not found to have any definite relation to the nature of the rape, its violence or defensive actions made by the women. As compared with the frequency of psychological sequelae described in the literature, only few women sought psychological aid. The explanation of this may be problems in organization at the commencement of the new arrangement. PMID- 2916258 TI - [A case of scurvy occurring during prolonged hospitalization]. AB - A case of scurvy during prolonged stay in hospital is presented. Symptoms and treatment of manifest scurvy and prophylactic therapy are discussed. PMID- 2916259 TI - [Common bile duct cyst of type 1]. AB - A case of common bile duct cyst, type 1, is presented. On account of the risk of development of cancer, excision of the cyst and the gall bladder is recommended. The duct system is then reestablished by means of hepato-jejunostomy. Scandinavian gastroenterologists should bear this condition im mind in patients of Asiatic origin with signs of biliary disease. PMID- 2916260 TI - [Intrauterine tachycardia--differential diagnosis from fetal death]. AB - A case of intrauterine tachycardia is presented. The case was primarily diagnosed as one of foetal death. The correct diagnosis was established by ultrasonic scanning. During the neonatal period, the Wolff-Parkinson-White syndrome was diagnosed. This is a common cause of intrauterine tachycardia. PMID- 2916261 TI - [Sudden infant death. Vascular etiology because of inactivity?]. PMID- 2916262 TI - [Renal cysts]. PMID- 2916263 TI - [Screening of cancer, advantages and disadvantages]. PMID- 2916264 TI - [Rational use of medical technology]. PMID- 2916265 TI - [Education in psychotherapy and research institutes in public regime]. PMID- 2916266 TI - [Greenland--a land without physicians? A new agreement, wishes-- a new solution to big problems!]. PMID- 2916267 TI - Genitourinary prostheses. PMID- 2916268 TI - The artificial urinary sphincter. Experience in adults. AB - The author's experience and results of implanting the artificial sphincter into 406 adults from June 1972 through March 1988 are reviewed. The early experience in which the device was pressurized by means of valves has been compared with later experience with the device whose pressure is controlled by means of a balloon. The degree of continence has been assessed according to the model of the device, the etiology of the incontinence, the location of the cuff, and the pressure that was chosen. The patients have been grateful to achieve an improved quality of life with social urinary continence brought about by improvements in the prosthesis. Additional improvements in the fitting of the cuff might bring even better results. PMID- 2916269 TI - The artificial sphincter (AS-800). Experience in children and young adults. AB - From reviewing our experience in the application of the AS-800 sphincter for the management of incontinence in children, we conclude that implantation is indicated after conservative and less invasive therapy has been attempted. The bladder neck is the site of choice for cuff placement in children. Primary deactivation and moderate or low reservoir pressures (61 to 70 and 71 to 80 cm H2O) are indicated, especially in patients with previous bladder neck surgery or an inadvertent bladder neck injury. Excess residual urine should be evacuated by clean intermittent catheterization. The AS-800 is mechanically reliable (9 mechanical failures in 45 sphincters). When the sphincter is implanted in a select group of patients, upper tract function is maintained in a stable state. Detubularized augmentation cytoplasty must be used to supplement the sphincter in patients with low-compliance, low-capacity, and nonresponsive hyperreflexic bladders. In all patients, long and careful follow-up is necessary to identify late changes in bladder function and consequent upper tract damage. An overall satisfactory result (fair to good) was obtained in 88 per cent of patients during an average follow-up period of 35 months, and 0.6 modifying procedure per patient was done in the sphincters. PMID- 2916270 TI - Semirigid and malleable rod penile prostheses. AB - Rod penile prosthesis implantation has a high functional success rate, and the devices have a low mechanical failure rate. The rods are easily implanted. Transient problems, such as pain or penile edema lasting longer than 4 weeks, occur in 10 to 15 per cent of patients, and serious complications such as infection or prosthesis erosion occur in 1 to 5 per cent. PMID- 2916271 TI - Testicular prostheses. AB - Testicular prosthesis implantation is a generally simple and low-morbidity method of softening the psychological trauma suffered by patients faced with the loss of a testis. PMID- 2916272 TI - Development of a penile prosthesis. The Hydroflex. AB - The development and commercialization of a penile prosthesis is a long and involved process that is influenced by a large number of factors including the patient, surgeon, FDA, commercial viability, and competitive environment. The process is illustrated in this article by historically tracing some of the factors involved in the development of the American Medical Systems self contained penile prosthesis, the Hydroflex. This device was introduced into unrestricted commercial distribution in May 1985. PMID- 2916273 TI - Legal aspects of urologic prosthetic devices. AB - Although tools may be one of the major progenitors of civilization, they certainly can, in the medical arena, give rise to a wide variety of legal controversies, including malpractice claims, suits for lack of informed consent, and actions against manufacturers for breaches of warranty and strict liability. This article has reviewed briefly some of these complex legal issues in light of the continuously changing status of medical device litigation. PMID- 2916274 TI - Bone fixation technique for transvaginal needle suspension. AB - The transvaginal needle suspension procedure coupled with the bone fixation technique provides excellent restoration of continence without causing outflow obstruction. The surgical procedure is precise, with a significant decrease in postoperative pain and discomfort when the pubic tubercle is utilized as the fixation point for the suspension sutures. PMID- 2916275 TI - The OmniPhase and DuraPhase penile prostheses. AB - The OmniPhase and DuraPhase prostheses can be classified as mechanical penile implants. They offer the features of ease of insertion, simple operation requiring little or no manual dexterity, good intrinsic axial rigidity, and exceptional concealability. The bendability of both devices resembles the twisting of a gooseneck lamp. As they are both mechanical devices, they impart a firmness to the penis at all times, as opposed to the fluid feeling of the hydraulic devices. The mechanical reliability of each model has been good to date, and the simplicity of manipulation has made this class of devices the choice of many impotent patients. PMID- 2916276 TI - The Hydroflex penile prosthesis. AB - Since its introduction in 1985, the Hydroflex penile prosthesis has become a popular choice of impotent patients. Simplicity of insertion, mechanical reliability, and the ability to give alternate firmness and flaccidity to the penis account for its widespread acceptance. Selection of patients is important, excluding those with impaired manual dexterity who would become frustrated in learning to operate the inflation-deflation mechanism of this device. Also, this prosthesis is somewhat bulky and cannot be crammed satisfactorily into the unusually small penis. When turgid, it does not expand beyond fixed limits and so would not fill the exceptionally large penis, resulting in a relatively unstable erection in such a patient. Appropriate sizing of the cylinders, especially the width, is important for a successful outcome. PMID- 2916277 TI - The Flexi-Flate and Flexi-Flate II penile prostheses. AB - Our experience with 45 recipients of the Flexi-Flate and Flexi-Flate II prostheses leads us to the following conclusions: 1. The device is readily implantable in approximately 1 hour with techniques familiar to most urologists who have implanted rigid or semirigid rods. 2. With attention to detail, prosthesis sizing is straightforward using intraoperative determination of corporeal girth and total corporeal length. We were unable reliably to predict prosthesis size preoperatively. Hence, as with other inflatable prostheses, we recommend that an entire range of prosthesis sizes be available at implantation. 3. Mechanical reliability is similar to that of more complex inflatable devices. The mechanical malfunction rate has been 11.6 per cent over a 15.1-month follow up. 4. Patients find the inflation-deflation mechanisms easy to master. 5. Spontaneous deflation does occur during intercourse in some instances, but most patients are able to adjust sexual techniques and position satisfactorily with minimal disruption of enjoyment for themselves and their partners. 6. Among individuals with functional prostheses, a detailed survey of patient and partner response postoperatively revealed a high level of satisfaction for both and a return to premorbid levels of sexual functioning. Concealability was good in the flaccid state, and patients report minimal difficulties or embarassment with everyday functions in public restrooms and shower situations. PMID- 2916278 TI - Mentor inflatable penile prostheses. AB - The standard Mentor inflatable is an extremely reliable prosthesis that will provide complete satisfaction in 87 to 99 per cent of the patients in whom it is implanted. The proved long-term reliability and superior functional characteristics of the three-component Mentor prosthesis make it a standard investigators may use to compare the recently introduced mechanical and modified inflatable prostheses. The short-term results of the new Mentor GFS prosthesis also are encouraging. The new prosthesis provides an attractive alternative to the standard inflatable prosthesis in patients with normal-sized genitalia, especially for surgeons who prefer to implant the device through a penoscrotal incision. PMID- 2916279 TI - Clinical experience with controlled expansion cylinders. The AMS 700 CX inflatable penile prosthesis. AB - Device manufacturers continue to look for modifications in design to achieve specific objectives directed at improving overall reliability. Changes in design that do not address this extremely significant concern, namely, device reliability, fail in their commitment toward improvement in patient satisfaction. One of the most effective ways to assess the benefits provided by any change in device design is through the clinical trial and study group method, utilizing a large number of implanting surgeons from a variety of backgrounds and with a variety of patients. The results of the clinical trials with the AMS 700 CX cylinders were extremely encouraging. More importantly, the findings of the study group and our own findings have been substantiated through widespread clinical application among an even larger number of implanting physicians. Device reliability should continue to be under serious scrutiny. We, as implanting physicians, are constantly being asked by our patients, "How long can I expect this device to function?" The answer can only be given on the basis of reports such as this and others that address the results of implantation in a series of patients who are followed appropriately year after year. Each year these reports, if brought up to date, will become even more meaningful. Meanwhile, new designs continue to be evaluated in the laboratory and will become a reality only through the suggestions provided by implanting surgeons, whose observations, when relayed to the manufacturer, enable the design engineer to address the specific concerns of both patient and physician. The AMS 700 CX inflatable penile prosthesis with its new controlled expansion cylinders has certainly addressed those concerns for the present. PMID- 2916280 TI - Penile prostheses. An overview. AB - Penile prosthesis implantation in selected patients can achieve very gratifying results. Satisfactory surgical results can be obtained in a high percentage of cases, and if the patient and his partner are well informed preoperatively, patient and partner satisfaction can also be very good. PMID- 2916281 TI - Corporeal reconstruction procedures for complicated penile implants. AB - Implantation of a penile prosthesis is now a very much accepted mode of management of organic erectile impotence. In most situations, this operation will involve little or no corporeal reconstruction. However, in the presence of more severe pathologic processes that may lead to corporeal damage, such as infective corporitis secondary to an earlier penile prosthesis or postpriapism fibrosis, and with the increasing public awareness of the availability of therapeutic modalities for impotence, the urologist must be well versed in the diagnostic and surgical techniques of corporeal reconstruction. PMID- 2916282 TI - Sex therapy for the penile prosthesis recipient. AB - In conclusion, the evidence for technical success of the penile prosthesis is clear, but more detailed follow-up studies suggest that a large minority of patients and partners fail to achieve sexual satisfaction. If the goal of surgery is to restore sexual frequency, variety, and pleasure to optimal levels, an integrated treatment program that incorporates sex therapy may be more successful than implantation alone. The type of sex therapy required depends on the risk factors present for postsurgery sexual dissatisfaction. A majority of patients can benefit from several sessions of brief sexual counseling preoperatively, with routine follow-up at 3 and 6 months after surgery to identify problems in resuming sex successfully. I also would point out that an integrated treatment approach is just as applicable to home intracavernosal injection programs. Including sex therapy in the package might reduce the large drop-out rates currently being seen and might decrease the risk of misuse of these medications. PMID- 2916283 TI - History of the prosthetic treatment of urinary incontinence. AB - Prostheses for the treatment of urinary incontinence have evolved from early passive compressive devices, which were limited to use in men, to the current AS 800, which is suitable for both sexes. The device represents continued improvement and streamlining of several earlier models. Parallel advances in surgical technique and perioperative management have made prosthetic treatment of urinary incontinence a well-recognized and desirable solution for a difficult urologic problem. PMID- 2916284 TI - Assessment of male infertility: correlation between results of semen analysis and phosphorus-31 magnetic resonance spectroscopy. AB - To evaluate the usefulness of phosphorus-31 magnetic resonance spectroscopy (31P MRS) in assessing male infertility, we compared it with conventional semen analysis. Specimens were obtained from otherwise healthy patient groups as follows: group A, 7 fertile control subjects; group B, 12 azoospermic men after vasectomy; and group C, 11 patients presenting for infertility evaluation. Correlations between established semen analysis parameters and the 31P-MRS derived ratio of glycerylphosphorylcholine to total phosphate (GPC/TP) were investigated. Group A controls had a mean GPC/TC ratio of 0.10 +/- 0.05, which was the same as that of group C. With the exception of significantly lowered motility and normal morphology in group C (p less than 0.001 and 0.05, respectively) semen analysis parameters in these two groups were similar. In contrast, the GPC/TP ratio in group B (0.05 +/- 0.04) was significantly different from the control (p less than 0.05), which appropriately reflected complete vasal occlusion. The results suggest that a significant portion of seminal GPC is derived from epididymal secretion and that 31P-MRS is useful for monitoring the GPC/TP levels when assessing epididymal function and male infertility. PMID- 2916285 TI - Complete hemorrhagic necrosis of renal adenocarcinoma following percutaneous biopsy. AB - We report a case of renal adenocarcinoma diagnosed by percutaneous biopsy, under computerized tomography (CT) guidance. The pathology following nephrectomy revealed only hemorrhagic necrosis. The implications of this occurrence are presented. PMID- 2916286 TI - Paratesticular metastases from congenital retroperitoneal tumor. AB - A retroperitoneal tumor was removed from a fifteen-day-old infant. Light microscopy revealed a teratoma consisting mainly of immature nervous tissue. Three months later the patient had recurrence and numerous peritoneal metastases showing a histologic pattern similar to that of the primary tumor. Twelve months later there was enlargement of the left testis due to metastases from teratoma infiltrating the tunica vaginalis of the left testis, the epididymis, and the spermatic cord. These metastases consisted of mature neurons and glial cells. The early dissemination of the tumor suggests an intracavitary spread pattern. The tumor maturation in paratesticular structures suggests that mesothelial cells are involved in the differentiation of tumoral germ cells. PMID- 2916287 TI - Spontaneously reduced testicular torsion. A pitfall in radionuclide scrotal imaging. AB - The radionuclide scrotal scan is highly accurate in the differential diagnosis of acute torsion vs epididymo-orchitis. While the scan findings of increased flow through the spermatic cord and increased static scan activity suggest inflammation, its appearance is not always diagnostic of inflammatory disorder. That this may also occur after reduction of torsion has not been emphasized in the literature. A case report of spontaneous reduction of testicular torsion is presented which demonstrates both increased flow and increased static image activity mimicking epididymitis. PMID- 2916288 TI - Spontaneous regression of pulmonary metastases from renal cell carcinoma. AB - One year after nephrectomy for renal cell carcinoma in a seventy-year-old man pulmonary nodules developed which proved to be metastases by needle biopsy. Chest radiographs thirteen and eighteen months later revealed complete spontaneous regression of the nodules without therapy. PMID- 2916289 TI - Use of cystoscopy sheath in radical retropubic prostatectomy. PMID- 2916290 TI - Technique for more rapid localization of distal ureteral obstruction with excretory urography. PMID- 2916291 TI - Absolute ethanol renal angioinfarction for control of hypertension. AB - Six patients (11 renal units) underwent ethanol renal angioinfarction for medically uncontrollable hypertension. The mean preablation blood pressure was 175/112 mm Hg despite antihypertensive medications. Five of the patients demonstrated elevated renal vein renin levels prior to angioinfarction. Hypertension was improved in all 6 patients, during a mean follow-up period of fifty-one months. Systemic hypertension was completely eliminated in 4 patients. Two patients continue to require antihypertensive medication to control their hypertension. There were no major complications directly related to intra arterial injection of ethanol. Transcatheter renal ablation employing intra arterial injection of absolute ethanol for control of severe hypertension appears to be a safe and efficacious procedure. It should be considered an alternative to nephrectomy in selected high-risk patients. PMID- 2916292 TI - Six-microtransducer catheter connected to computer in evaluation of urethral closure function of women. AB - A new instrument consisting of a six-transducer catheter, one transducer for the bladder and five transducers for urethral pressure recordings, and a computer with specific software was developed for urodynamic investigation of women. Twenty-six patients with stress urinary incontinence (SUI) and 10 continent female patients were evaluated during the single cough, the first and the fourth ones of the forced coughings in supine and standing positions. The results were compared with those obtained with the conventional two-transducer method. Negative urethral closure pressure (UCP) at stress, indicative of SUI, was present in 88 percent of the cases with the six-transducer method, and in 77 percent with the two-transducer method. The fourth cough in the standing position with the six-transducer method was most diagnostic. In SUI, the six-transducer method indicated exactly, e.g., the minimum bladder pressure needed for negative UCP and the duration of negative UCP. Patients with SUI had significantly lower UCP at rest, UCP at stress, and pressure transmission ratio (PTR) than continent women. Findings, that UCP at stress decreased and duration of negative UCP at stress increased but PTR did not change when the fourth cough was compared with the first one in SUI, suggest that factors which are responsible for the altered urodynamics during prolonged stress are anatomic rather than functional. PMID- 2916293 TI - Renal trauma assessment. PMID- 2916294 TI - Special considerations for implantation of 12 cm and 15 cm AMS 700 CX cylinders. PMID- 2916295 TI - Prospective study of metabolic abnormalities in patient with continent Kock pouch urinary diversion. AB - Metabolic alterations as a result of bowel being employed in the urinary tract are well documented. To investigate this phenomenon in the continent ileal reservoir urinary diversion, 106 patients who had undergone Kock pouch surgery were followed in a prospective study at the University of Southern California between 1985 and 1987. Serum chemistries and urine osmolality determinations were performed approximately every three months for a year. Mean patient values for each time period were then compiled and compared with the norms and with the preoperative values. The mean serum electrolyte values were found to be within normal limits during all follow-up periods. Fourteen patients were identified, however, as having values falling intermittently outside of the normal range. These patients were investigated and found to be abnormal during episodes of acute renal failure usually secondary to dehydration or obstruction at which time they usually became acidotic and occasionally hyperchloremic. These problems disappeared when the renal failure was corrected. This study corroborated our previously reported findings that hyperchloremic acidosis or other metabolic alterations requiring replacement therapy do not routinely occur in this population. PMID- 2916296 TI - Flow cytometric study comparing paired bladder washing and voided urine for bladder cancer detection. AB - Paired bladder washings and voided urines from bladder cancer patients were compared as sources of exfoliated cells for detection of bladder carcinoma by flow cytometry (FCM). Bladder specimens fixed in 25% ethanol within sixty minutes of collection were found to be superior to unfixed bladder specimens. The percentage of specimens with good DNA resolution was greater for bladder washings (67% unfixed, 90% fixed) than voided urines (41% unfixed, 66% fixed). There was no difference in DNA resolution between specimens that remained unfixed less than one day, one day, or two days suggesting that the cells undergo the majority of degradation within a critical period soon after collection. Once fixed, there was no difference in DNA resolution for up to nineteen days, which suggests the feasibility of specimen transport to central FCM laboratories. Eighteen percent of unfixed bladder washings and 33 percent of unfixed voided urine specimens contained an insufficient number of cells (less than 5,000) at the time of analysis compared with 6 percent bladder washings and 17 percent voided urines fixed in 25% ethanol. Flow cytometry and cytology results were concordant in 28/43 (65%) of fixed bladder washings and 9/13 (69%) of fixed voided urine. Voided urine was unreliable in providing consistent FCM data due to the high number of specimens with poor resolution or insufficient cells and is not recommended as a substitute for bladder washing when screening high-risk populations or monitoring patients with past history of bladder cancer. PMID- 2916297 TI - New apparatus to reduce urinary drainage associated with urinary tract infections. AB - The automatic release of povidone iodine (PVP-I) into the outlet tube of a urinary collecting bag significantly reduced urinary tract infections (UTIs) and provided a more practical bacterial barrier than manual instillation of PVP-I into the bag as used previously. In 52 patients using a new urinary drainage system with a cartridge that released PVP-I into the outlet tube of the collection bag UTIs developed in 3, compared with 57 patients using a standard closed drainage system and in whom 13 UTIs developed (p less than 0.005). The PVP I group had 92 percent of the accumulative catheter-days free of bladder infection, compared with 77 percent in the standard group. The main route of bacterial contamination leading to urinary drainage UTIs was through the collection bag. PMID- 2916298 TI - Alternative site for the single intradermal comparative tuberculin test in the llama (Llama glama). PMID- 2916299 TI - Diagnosis of freemartinism in sheep. PMID- 2916300 TI - Cobalt deficiency and Ostertagia circumcincta infection in lambs. PMID- 2916301 TI - CFC pollution: vets at fault? PMID- 2916302 TI - Immobilon supply to holders of Home Office licensed dart guns. PMID- 2916303 TI - MoD grant to Bristol veterinary school. PMID- 2916304 TI - Salmonella in poultry. PMID- 2916305 TI - Right to dispense. PMID- 2916306 TI - Cat deaths: toxicity or ...? PMID- 2916307 TI - Intratracheal antibiotic treatment. PMID- 2916309 TI - Speaking up for the profession. PMID- 2916308 TI - Fasciola hepatica infestation. PMID- 2916310 TI - An evaluation of tympanometry, otoscopy and palpation for assessment of the canine tympanic membrane. AB - Three techniques for the assessment of the integrity of the canine tympanic membrane were evaluated experimentally. Tympanometry, an objective technique, was shown to be very accurate for the evaluation of the integrity of the ear drum. Otoscopic examination by experienced personnel was shown to be moderately accurate under controlled conditions when the external ear canal was not inflammed. However, under field conditions when otitis externa was present, visual inspection of the tympanic membrane was seldom possible even after lavage of the ear. Palpation of the tympanic membrane with a blunt probe was shown to be very inaccurate and led to rupture of the tympanic membrane in a high proportion of cases. These results imply that two widely used techniques for the examination of the canine tympanic membrane are unsatisfactory. Furthermore, they suggest that previous reports of the prevalence of ear drum perforations in dogs may need reappraisal. Tympanometry is a non-invasive, objective and practical technique for the assessment of ear drum integrity which is worthy of further evaluation. PMID- 2916311 TI - Acute nephropathy in young lambs. AB - Acute renal failure was diagnosed by clinical, necropsy and histological criteria in 39 flocks (20 low ground, 13 hill and six marginal upland) in areas served by six veterinary investigation centres. Forty-eight lambs of 12 different breeds or crosses were investigated. The mean age of affected lambs was 38 days (range seven to 84 days); 21 lambs (44 per cent) were aged seven to 28 days, while only eight (17 per cent) were older than two months. Mortality in clinically affected lambs was almost 100 per cent, with no response to various treatments. Histological examination showed that 40 lambs (83 per cent) had nephrosis, while the rest had toxic tubular necrosis, interstitial nephritis or tubular damage associated with oxalate crystal deposits. Only about half of the lambs had any evidence of enteric infections or enteropathy. Acutely ill lambs had azotaemia, haemoconcentration and proteinuria; some lambs had glycosuria or haematuria. Samples of plasma from 22 lambs with nephrosis were compared with similar samples from 82 incontact but asymptomatic lambs. The clinically affected group had significantly elevated plasma urea, creatinine, total protein, globulin, phosphorus and chloride concentrations and significantly reduced plasma calcium concentrations compared with healthy lambs. Affected lambs had a significant reduction also in the calcium:phosphorus ratio. No significant differences between groups was found in plasma concentrations of albumin, glucose, lactate, glycerol, creatine kinase, alkaline phosphatase, sodium, potassium or magnesium. PMID- 2916312 TI - Building a practice. Budget forecasts and performance monitoring. AB - In order to run a small business effectively you must be in financial control and this means that you have to be aware how the business is performing. If you wait until your accountant has got out the annual accounts valuable time has been wasted in making necessary decisions and corrections to poor trends in your business so monthly/quarterly records are required. Decisions as to whether you can afford to take another assistant, set up a branch surgery, the level of your fee increases, whether to buy or lease your cars; are all dependent on having available up to date financial knowledge of your business. If you have a microcomputer in the practice you can use spreadsheets which will allow the accurate prediction of cash flow or profitability. You can also ask the question 'what happens if...?' and get the answer in seconds. But even without a computer, financial control can be easily maintained if you are prepared to spend a couple of hours each month with your practice figures. PMID- 2916313 TI - Influence of biotin supplementation on pig claw horn: a scanning electron microscopic study. AB - Observations made with a scanning electron microscope of the claw horn and underlying soft tissues of young pigs fed a normal diet supplemented with 1 mg d biotin/kg of feed were compared with observations on a similar group receiving no additional biotin. Supplementary biotin affected the structure of the coronary epidermis; there was an increase in the density of the horn tubules in the stratum medium, the horny squames in the stratum medium were more tightly packed and the tubules were more clearly defined in the pigs receiving biotin. The width of the band of intertubular horn adjacent to the laminae was greater in the claws of control pigs. PMID- 2916314 TI - Nasal cavernous haemangioma in an American short haired cat. PMID- 2916315 TI - Malignant catarrhal fever in a roan antelope (Hippotragus equinus) at Regent's Park. PMID- 2916316 TI - Bovine tuberculosis in deer. PMID- 2916317 TI - Salmonella in poultry. PMID- 2916318 TI - SPVS/BSAVA survey. PMID- 2916319 TI - Outbreak of sheep pulmonary adenomatosis in the Irish Republic. PMID- 2916320 TI - Exotic and wild animal society. PMID- 2916321 TI - Salmonella infection in a vet. PMID- 2916322 TI - Wildlife rehabilitation. PMID- 2916324 TI - Dearth of veterinary surgeons. PMID- 2916323 TI - Small animal dentistry. PMID- 2916325 TI - Lymphocytic choriomeningitis virus selectively alters differentiated but not housekeeping functions: block in expression of growth hormone gene is at the level of transcriptional initiation. AB - Persistent infection with lymphocytic choriomeningitis virus (LCMV) Armstrong strain in C3H/ST mice is associated with a growth hormone (GH) deficiency syndrome, characterized by growth retardation and low serum glucose levels (M.B.A. Oldstone et al., 1982, Science 218, 1125-1127). The syndrome is associated with a decrease in GH synthesis in the pituitary gland, in the absence of cellular injury in the pituitary or associated brain areas. In this report, we demonstrate that the decreases in steady-state synthesis of GH and its mRNA in virally infected mice is related to a 16-fold reduction in initiation of transcription of this gene. Minimal decrease, however, was demonstrated in transcriptional initiation of another pituitary gene, the precursor of thyroid simulating hormone (TSH-beta) or of the housekeeping genes, actin and pro alpha 2(I) collagen. Thus, viruses can cause disease in the absence of cytolytic or morphologic injury by selectively disrupting the synthesis of a differentiated cellular product at the level of transcriptional initiation. PMID- 2916326 TI - Mutations at the cleavage site of the hemagglutinin after the pathogenicity of influenza virus A/chick/Penn/83 (H5N2). AB - Six variants that form plaques in chick embryo cells in the absence of trypsin have been isolated from the apathogenic avian influenza virus A/chick/Pennsylvania/1/83 (H5N2). Unlike the wild-type, the plaque variants contain a hemagglutinin that is cleaved in chick embryo cells and MDCK cells. The variants differ also from the wild-type in their pathogenicity for chickens. Nucleotide sequence and oligosaccharide analysis of the hemagglutinin have revealed that, unlike natural isolates with increased pathogenicity (Y. Kawaoka et al., 1984, Virology 139, 303-316; Y. Kawaoka and R. G. Webster, 1985, Virology 146, 130-137), the variants obtained in vitro have retained an oligosaccharide at asparagine 11 that is believed to interfere with the cleavage site of the wild type. However, all variants showed mutations in the hemagglutinin resulting in an increased number of basic groups at the cleavage site. These observations demonstrate that masking of the cleavage site by an oligosaccharide is overcome by an enhancement of the basic charge at the cleavage site. PMID- 2916327 TI - Control of reovirus messenger RNA translation efficiency by the regions upstream of initiation codons. AB - The 10 species of reovirus messenger RNA are translated in vivo with efficiencies/frequencies that differ by as much as 100-fold. The s1 mRNA, which is translated 10 times less efficiently than the s4 mRNA but 10 times more efficiently than the/1 and m1 mRNAs, has a unique BamH1 cleavage site located immediately downstream of its initiation codon. Because the reovirus mRNAs have been cloned, this provides the opportunity for placing modified and altered sequences upstream of its coding sequence. The translation efficiencies of the variant mRNAs, transcribed via the SP6 in vitro transcription system, can then be measured in the rabbit reticulocyte lysate in vitro translation system. Using this system it was found that replacing the 5'-upstream sequence of the s1 mRNA with that of the s4 mRNA increases its in vitro translation efficiency by 4-fold; that the trinucleotide immediately upstream of the s1 initiation codon renders it very weak, and that it is only slightly superior to the weakest Kozak consensus sequence; that the nature of the nucleotides further upstream than position -3 can profoundly affect translation efficiency; that the nature of this effect is in turn markedly modified by the nature of nucleotides in positions -1 to -3; and that there is a minimum optimal 5'-upstream sequence length of about 14 nucleotides. We also investigated the effect of secondary structure involvement on the ability of 5'-upstream sequences to promote translation. Two effects were noted. First, being part of moderately stable stem loops (delta G, -18 kcal/mol) decreased translation efficiency about 3-fold; second, mRNA in which only three 5'-terminal nucleotides were unpaired were translated five times less efficiently than mRNA in which six nucleotides were unpaired. Accessibility of the 5'-cap as well as secondary structure of the 5'-upstream sequences are therefore factors that affect translation efficiency. Finally, we showed that the m1 mRNA, which is transcribed very poorly in vivo, is translated very efficiently in vitro; and that its 5'-upstream sequence is as effective in increasing protein sigma 1 formation as that of s4 mRNA. Since both m1 mRNA and protein mu 2 are stable in infected cells, the reason why m1 mRNA is translated so inefficiently in vivo therefore remains unexplained. PMID- 2916328 TI - Intraviral homology and subgenomic RNAs of pepper ringspot virus. AB - The Tobraviruses constitute a group of rod-shaped, bipartite, plus-stranded RNA viruses. We report on homologies between the two viral genomic RNA molecules of pepper ringspot virus (PRV) and on the subgenomic components generated from them during infection. It has previously been shown that the 3'-terminal 459 nucleotides of PRV RNA-1 and RNA-2 are identical. Here it is shown that there is a second homology between RNA-1 and a region of RNA-2, located at least 240 nucleotides downstream from its 5' terminus. In agreement with strains in another Tobravirus group, we observe three subgenomic components in extracts of plants infected with PRV. Two of these, RNAs-1a (1.6 kb) and -1b (0.8 kb), are derived from RNA-1 (the larger genomic RNA). They are probably mRNAs for 29- and 16-kDa nonstructural virus proteins. The smaller genomic RNA, RNA-2, generates the subgenomic component RNA-2a (1.3-1.45 kb) which is probably an efficient capsid protein mRNA. Previously reported subgenomic components of 2.8 and 1.1 kb are shown to be electrophoretic artifacts. RNA-2a, but not 1a or 1b, is present in virion RNA preparations, indicating that it is the only subgenomic species to be encapsidated. PMID- 2916329 TI - Chlorella viruses contain linear nonpermuted double-stranded DNA genomes with covalently closed hairpin ends. AB - Pulsed field electrophoresis established that Chlorella viruses contain linear, nonpermuted, 330- to 380-kb dsDNA genomes. Terminal DNA restriction fragments of one virus, PBCV-1, were identified by Bal31 exonuclease digestion; the termini probably contain covalently closed hairpin ends. The end fragments cross hybridize indicating terminal repetition; the region of repetition extends no more than 2.5 kb from the ends. PMID- 2916330 TI - Localization of multiple TMV encapsidation initiation sites on rbcL gene transcripts. AB - TMV capsid protein reacts with and encapsidates many of the chloroplast DNA transcripts both in vivo and in vitro to form pseudovirions. We report on the encapsidation initiation reaction with one of the major RNA species found in in vivo formed pseudovirions, the mRNA for the chloroplast-encoded large subunit of ribulose bisphosphate carboxylase/oxygenase (rbcL). This mRNA is found to contain at least three sites which are independently capable of reacting with capsid protein oligomers to initiate encapsidation. All three sites react with capsid protein less efficiently in vitro than does the functional viral RNA encapsidation initiation site (ei). The 5' portion of the region that contains the most reactive rbcL site, ei-3, shows significant nucleotide sequence homology with the encapsidation initiation sites of the U1 and Cc strains of TMV and it can assume a folding structure that resembles that postulated for the Cc strain site. A site that acts as a block to rod elongation is present in transcripts from the region just 3' to the segment from which the rbcL mRNA is transcribed, probably close to, or at the transcription termination signal. PMID- 2916331 TI - Saturable binding sites mediate the entry of African swine fever virus into Vero cells. AB - Binding experiments of 3H-labeled African swine fever virus to susceptible VERO cells have shown the presence of saturable binding sites for African swine fever virus on the plasma membrane. The Scatchard analysis of the binding data at equilibrium indicates the existence of about 10(4) cellular receptor sites per cell with a dissociation constant (Kd) of 70 pM. Virus entry into VERO cells is mediated by a saturable component, since tritiated African swine fever virus saturable binding and uptake were competed by the same amounts of unlabeled virus. Similarly, early viral protein synthesis and virus production were inhibited by concentrations of uv-inactivated virus that competed virus attachment to saturable binding sites, suggesting that specific receptors mediate the entry of African swine fever virus particles that initiate a productive infection in VERO cells. African swine fever virus binding to virus-resistant L cells was not mediated by saturable binding sites. As a result of the nonsaturable interaction the virus was not able to enter L cells and neither early viral protein synthesis nor viral DNA synthesis was detected, indicating that the absence of specific receptors for African swine fever virus is a factor that determines the resistance of L cells to the infection. PMID- 2916332 TI - African swine fever virus-induced proteins on the plasma membranes of infected cells. AB - The African swine fever virus-induced proteins on plasma membranes of infected cells have been studied by two different procedures, iodination and incubation of infected cells labeled with [35S]methionine with a specific antiserum, obtained from pigs immunized with a monkey stable cell-adapted African swine fever virus. The combined use of both procedures identified proteins IP56, IP51, IP35, IP34, IP31, IP30, IP25.5, IP23.5, IP16, IP15, IP14, and IP12 as viral antigens exposed on the surface of infected cells. Proteins IP16, IP15, and IP14 were recognized by the immune serum from survivor pigs, obtained after challenge with homologous virulent virus, but not by the immune serum from the same pigs immunized only with the cell-adapted virus. PMID- 2916333 TI - Nucleotide sequence of the Lassa virus (Josiah strain) S genome RNA and amino acid sequence comparison of the N and GPC proteins to other arenaviruses. AB - The complete nucleotide sequence of the S genome RNA of the Josiah strain of Lassa virus was determined from cloned cDNA. The S RNA is 3402 nucleotides long with a calculated molecular weight of 1.09 x 10(6) Da. The nucleotide base composition is 26.84% adenine, 21.40% guanine, 22.75% cytosine, and 29.01% uridine. The 5' and 3' terminal nucleotide sequences are conserved and complimentary for 19 nucleotides, the nucleoprotein and glycoprotein genes are arranged in ambisense coding strategy, and the intergenic region contains an inverted complimentary sequence, as do all other arenavirus S RNAs characterized to date. Amino acid sequence comparisons between the nucleoproteins and glycoproteins of the Josiah and Nigerian (N sequences only) strains of Lassa virus, the WE and ARM strains of lymphocytic choriomeningitis virus (LCMV), Tacaribe, and Pichinde viruses are presented. These findings reveal that the G2 envelope glycoprotein is more conserved among different arenaviruses than the internal nucleoprotein. PMID- 2916334 TI - A new cellulose acetate filter to remove leukocytes from buffy-coat-poor red cell concentrates. AB - Transfusion of leukocyte-free red cell concentrates (RCC) prevents or delays HLA immunization in multitransfused patients. We investigated a new cellulose acetate filter which was recently introduced to remove leukocytes from buffy-coat-poor RCC. It was found that the filtration time was only 10 min with buffy-coat-poor RCC in saline-adenine-glucose-mannitol (SAG M; n = 23), hematocrit being 62 +/- 2% (SD). The red cell loss was 13.5 +/- 2.6% and leukocyte removal was more than 99%. Routine filtration in SAG M (n = 179) showed again that more than 99% of the leukocytes were removed from buffy-coat-poor RCC with an original leukocyte content of 804 +/- (SD)458 x 10(6). The red cell loss (12 +/- 8.6%) was not diminished by increasing the amount of saline (0.9% NaCl) from 100 to 300 ml in an attempt to remove the retained red cells from the filter. We conclude that the new filter is reliable in rapidly removing more than 99% of the leukocytes from buffy-coat-poor RCC in SAG M solution. PMID- 2916335 TI - Thrombocytopenia following routine blood transfusion: micro-aggregate blood filters prevent worsening thrombocytopenia in patients with low platelet counts. AB - 11 patients with anaemia and thrombocytopenia due to bone marrow failure each received 2 sets of red-cell transfusions. They were randomised to receive 1 blood transfusion through a standard 170-micron giving set filter and another through a 40 micron micro-aggregate filter. After transfusion, the mean fall in platelet count was 15 x 10(9)/l (41.7%) and 1.4 x 10(9)/l (4.6%), respectively (p less than 0.01). The results confirm the findings of a previous study which showed that micro-aggregate filters prevent a post-transfusional decrease in platelet counts. In addition, this new study shows that this is clinically relevant in patients who are thrombocytopenic at the time of their blood transfusion. PMID- 2916336 TI - AIDS-related thrombocytopenia. Experience of a medium-term treatment with intravenous IgG in haemophilia B patients. PMID- 2916337 TI - Efficacy of the latest generation of antibody assays for (early) detection of HIV 1 and HIV 2 infection. PMID- 2916338 TI - [Free functional muscle transplantation with microneurovascular anastomosis: development of a standardized surgical procedure]. AB - Although investigated experimentally almost at the same time, free muscle transplantation without microvascular anastomoses was accepted as a clinical method earlier than muscle transplantation with microneurovascular anastomoses, which finally proved to be the method with better functional results in the late seventies. Our experimental investigations of different factors such as anoxemia, reinnervation, initial muscle tension, and of the functional capacity of this kind of muscle graft and of the time course of the alterations in the microsurgically vascularized muscle transplants influenced the operative concept for clinical application to a great extent. Besides general details of the operative technique, specific considerations with respect to the two main regions of clinical application namely the face and the extremities are presented. PMID- 2916339 TI - [Development of a physiological pacing concept at the 2d Surgical Department of the University of Vienna]. AB - With the transvenous approach of atrial leads in 1978 a progressive physiological pacing concept was developed at the Second Surgical Department of the University of Vienna. Using multiprogrammable fully-automatic double-chamber pacers and the technology of biological sensors, the most suitable treatment for any individual patient can be chosen. Our recommendations are DDD stimulation for complete AV block and rate-responsive pacing of the atrium or the ventricle for the Sick Sinus-Syndrome or atrial fibrillation, respectively. Second choices for AV block are rate-responsive single-chamber pacemakers or simple programmable pacemakers generally. PMID- 2916340 TI - [Infrarenal aortic aneurysm: results of surgical treatment]. AB - Between 1976 and 1987 93 patients with an infrarenal aortic aneurysm underwent surgical correction. In 62 patients the procedure was performed electively, whilst 13 displayed an unstable aneurysm and in 18 cases a ruptured aneurysm was present at operation. During the past 5 years the mortality was lowered to 2% in elective cases, whereas in cases of ongoing rupture only moderate improvement took place. The most frequent cause of a lethal outcome was pump failure of the heart (6 times), followed by renal insufficiency and haemorrhagic shock and bleeding complications. Among the non-lethal complications, relaparotomy on the basis of postoperative bleeding ranks first, followed by pulmonary insufficiency, peripheral emboli and partial ischemia of the spine. Resection of infrarenal aneurysms should be performed in the stable state of disease, since insufficiency of multiple vital organ systems increases the mortality by up to 20 fold. PMID- 2916341 TI - [Resection of pulmonary metastases: indications, surgical technic, results and prognostic factors]. AB - One hundred and ninety six thoracotomies were performed on 152 patients with pulmonary metastases up to 1988 in the Second Surgical Department, University of Vienna. Age ranged from 2 to 78 years, 13 patients were younger than 18 years. The primary tumour was carcinoma in 103 cases, sarcoma in 38 cases and melanoma in 11 cases. The primary tumour in young patients was osteosarcoma in 7 cases, Ewing sarcoma in 2 and Wilms tumour in 2 cases. With a minimal follow-up period of 2.5 years the actuarial 5 years survival rate of 37% was observed for carcinoma, and 29% for sarcoma patients. A statistical difference was found between the carcinoma and sarcoma groups with respect to survival rate; the prognosis for patients with melanoma was markedly worse. A prognostic factor was the duration of disease-free interval in carcinoma patients. Actuarial post thoracotomy survival in patients with osteogenic sarcoma was 32% at 5 years and only 10% in the soft-tissue sarcoma group. Size of lesions, vitality of the metastases and disease-free interval correlated with survival in the osteogenic group, whilst the number of lesions was of importance in the soft-tissue group. On account of the lesser functional morbidity and the ability to assess both lungs for exploration, palpation and resections, the importance of median sternotomy is constantly increasing for the treatment of pulmonary metastatic disease and the results justify an aggressive approach. In those cases which the primary tumour is sensitive to chemotherapy the procedure of metastatic resection must be incorporated into the general scheme of oncological therapy. PMID- 2916342 TI - [Reconstruction of deformities of the external ear]. AB - Microtia is a rare malformation. Reconstruction of microtia is not a routine operation because of its rarity of occurrence and the complex deformity. In this paper the indication for surgical treatment, technique, results and complications are discussed. Two different operation methods were used in our patients. A multiple-stage and a single-stage reconstruction procedure. We used autogenous rib cartilage. Five of the seven treated patients came to the follow-up examination. Reconstruction was performed 2 years ago in two cases and between 4 and 12 years ago in three cases. Our patients were content with the result in so far as they would be prepared to undergo treatment again. Carefully built rib framework is an essential prerequisite for a successful postoperative result. Microtia represents a greater psychological problem than a cosmetically imperfect result after reconstruction. PMID- 2916343 TI - [Acute cholecystitis in cholelithiasis: importance of early surgery (a comparative study)]. AB - The results of early surgery (ES) for acute calculous cholecystitis obtained in 74 patients operated on between 3/78 and 12/87 were compared with relevant data obtained in 74 sex- and age-matched patients with a history of acute cholecystitis operated on for biliary colic or jaundice during the same period. Operative procedures, incidence of jaundice and common bile duct calculi, duration of operation, number of patients requiring blood transfusions, surgical and general complications and mortality showed no significant difference. Only operative blood loss was significantly higher in the ES group, but this was of no practical relevance. ES precludes the sequelae of emergency surgery in the delayed surgery group not infrequently necessary for failure of conservative treatment of acute cholecystitis, which necessarily precedes planned delayed surgery, and thus renders a significant reduction of over-all risk. This forms the rationale for ES as treatment concept. PMID- 2916344 TI - [Ileus following radiotherapy: importance and therapeutic aspects of surgery for late radiation injuries of the intestine]. AB - Between 1971 and 1988 74 operations for intestinal complications following radiotherapy were performed on 67 patients at the Second Surgical Department, University of Vienna. The lesions were located in the small bowel (n = 41) and in the sigmoid colon/rectum (n = 33). 98.5% of the patients were females, the most frequent cause for irradiation being ovarian cancer. Bowel stenosis with resultant chronic or acute ileus was the most frequent indication for operation, occurring in 31 cases (76%) of the small bowel lesions and in 15 cases (46%) of the colon lesions. Percutaneous irradiation resulted in a significantly higher proportion of small bowel lesions (77%, p = 0.001), whilst endocavitary irradiation was followed in 67% of cases by colorectal lesions. Different application modality of irradiation also resulted in completely different symptoms for small and large bowel lesions. The operative mortality was 9.5%. Peritonitis following anastomotic leakage was the cause of death in 6 of 7 cases. In the treatment of small bowel ileus mortality following bowel resection (9%, one of 11 cases) was comparable to that of the bypass operation (6%, one of 18 cases). Both operation methods seem to be justified. Single-layer anastomosis resulted in zero mortality in 21 cases of ileus operated on by this technique, compared with 19% mortality in 16 cases treated by double-layer anastomosis and should be preferred for operations on the irradiated bowel. PMID- 2916345 TI - [12-year experience with continuous peritoneovenous shunt in the treatment of therapy-resistant ascites and hepatorenal failure: benefits and pitfalls]. AB - Theoretical advances using the peritoneovenous shunt were proven in clinical practice over a 12-year period of experience with this system. Continuous reinfusion of protein- and electrolyte-rich ascitic fluid improves the circulating plasma volume and seems to avoid hepatorenal syndrome. The quality of life is improved by the significant decrease in weight and ascitic volume: long time survival seems to be improved when compared with patient groups without treatment by continuous peritoneovenous shunt. Use of the system in patients with malignant ascites does not seem to be encouraging. Fatal postoperative coagulopathy can be avoided by the administration of proteinase inhibitors. Operative mortality was 0%, hospital mortality was 23%. The system became defective in 23%, 12% caused by intra-operative technical failures. PMID- 2916346 TI - [Breast-preserving treatment of breast carcinoma]. AB - Based on our 14-year experience with breast-preserving treatment of breast cancer, we recommend limited surgical intervention for the removal of a small mammary carcinoma under the proviso that adequate radiotherapy is available and that the patient can be thoroughly followed up. We are convinced that the good cosmetic result and especially the excellent psychological reaction are particularly important in order that women lose their fear of an ablative operation. Only then, by performing an operation which is not excessive at the earliest possible time can the prognosis of this type of carcinoma, which is increasing be improved. PMID- 2916347 TI - Wisconsin's family physician shortage. AB - This paper analyzes current and future needs for primary care physicians- particularly family practice physicians--in Wisconsin in light of predictions of a national physician glut by the year 1990. The current shortfall of family physicians is estimated to be at least 150, with the most severe deficits found in rural and underserved urban areas. Forty-nine to 79 family practice physicians will be needed each year to meet the growing demand and to replace losses due to retirement, speciality change, and other factors. At the current rate of training, 63 new family physicians will enter practice each year; it appears that the current deficit will be made up slowly, if at all. The number of primary care specialists appears unlikely to increase due to the declining interest in the speciality among medical students; only half the number of new family physicians entering practice each year will enter practice in 1994, resulting in an additional shortfall of about 30 to 50 family physicians each year. Programs should be undertaken at medical schools to bolster student interest in family practice and primary care. PMID- 2916348 TI - Exploring environmental cycles in psychiatric patients. AB - The daily psychiatric inpatient population at a large medical center recorded over a two-year period and consisting of 11,864 inpatient days was analyzed for circannual (365-day) and synodic (29.53-day) cycles. A highly significant circannual cycle, in which the population peaks in early February, was found. This cycle was compared to seasonal cycles of photoperiod, sunlight, and temperature and was found to be highly correlated with each. The best correlation was between patient population and photoperiod during the previous month. A significant synodic (lunar) cycle, with a peak in patient census occurring at the last quarter moon, was also found. PMID- 2916349 TI - Risk management: an ounce of prevention. PMID- 2916350 TI - Update on the medical mediation panels. PMID- 2916351 TI - Electronic information: Part II. PMID- 2916352 TI - AIDS estimates. PMID- 2916353 TI - The ethics of progress. PMID- 2916354 TI - What's our excuse? PMID- 2916355 TI - Child abuse reporting law needs changes. PMID- 2916356 TI - Spermatic granuloma. Diagnosis by fine needle aspiration cytology. AB - Spermatic granulomas may present as tumorlike lesions adjacent to the testis or seminal vesicle and are often associated with infection, trauma or previous surgery. The fine needle aspiration biopsy cytologic findings in three cases of spermatic granuloma are reported. The predominant cytologic features were granulomatous inflammation (nontuberculous and non-foreign body) and spermatozoids (intrahistiocytic or as extracellular spermatic debris). Additional features included lymphoid cells and lymphocytic debris (nuclear tangles), rare plasma cells and eosinophils. Germ cells and acellular (caseous) necrosis were not identified. Well-preserved sheets of epididymal epithelium were occasionally noted. The clinical and cytologic differential diagnoses in such cases are discussed. PMID- 2916357 TI - Breast carcinoma with tumor giant cells. Report of a case with fine needle aspiration cytology. AB - A 31-year-old woman presented with a cystic mass in the left breast. At fine needle aspiration (FNA), the mass felt gritty, and a firm mass remained after drainage of the cyst. Cytologic examination of the aspirate showed mononucleated malignant cells and an array of bizarre malignant multinucleated giant cells. A diagnosis of carcinoma of breast with malignant giant cells was made. Subsequent histologic study of the lesion showed a central cystic cavity lined by bizarre tumor giant cells. Immunocytochemistry and lectin cytochemistry confirmed the epithelial nature of the malignant giant cells. The entities that may yield giant cells on FNA of breast masses are discussed. PMID- 2916358 TI - Cytologic features of endometrial papillary serous carcinoma. AB - Endometrial papillary serous carcinoma (EPSC) is an uncommon variant of endometrial carcinoma that histologically resembles ovarian serous carcinoma and has an aggressive clinical course. The cytomorphologic features of 17 patients with histologically confirmed EPSC of the endometrium were reviewed and compared with those of 20 patients with histologically typical endometrial adenocarcinoma (TEC). Preoperative cervicovaginal Papanicolaou smear results were available from 14 of the 17 patients with EPSC; 10 (71%) were positive, 1 (7%) was suspicious and 3 (21%) were negative for malignancy. Initial cervicovaginal smear results were available from all 20 patients with TEC; 7 (35%) were positive, 4 (20%) were atypical or suspicious and 9 (45%) were negative for malignancy. Twelve patients with EPSC had peritoneal washings or fluids examined; seven were positive and five negative. Twelve patients with TEC had peritoneal washings or fluids examined; two (17%) were positive and ten (83%) were negative. The cervicovaginal smears from patients with EPSC revealed numerous large tumor cells (with prominent nucleoli) frequently arranged in papillary clusters with background necrosis and, in two cases, amorphous material suggestive of psammoma bodies. In contrast, the smears of patients with TEC showed small to medium-sized cells with extensive phagocytosis and many background histiocytes. The diagnosis of EPSC should be considered when the cervicovaginal smear contains numerous papillary groups of large tumor cells with macronucleoli but without prominent phagocytosis, especially when structures suggestive of psammoma bodies are present. The peritoneal fluids in these patients are more often positive than in patients with TEC, a finding consistent with the propensity of EPSC to involve peritoneal surfaces. PMID- 2916359 TI - Secretory carcinoma of the endometrium. AB - A case of secretory carcinoma of the endometrium in a 21-year-old woman is reported. Endometrial smears were interpreted as showing a differentiated adenocarcinoma. Smears of ascitic fluid obtained during subsequent surgery showed similar findings; periodic acid-Schiff staining of the smears revealed abundant positive material in the cytoplasm. These findings were interpreted as evidence of secretory carcinoma, which was confirmed by histopathologic study of the biopsy and surgical specimens. PMID- 2916360 TI - Cytology of clear cell carcinoma of the thyroid. PMID- 2916361 TI - Cytologic examination of endoscopic and colonoscopic biopsy supernates. PMID- 2916362 TI - Primary diagnosis of intraspinal echinococcosis by cytologic examination of cyst fluid. PMID- 2916363 TI - Pneumothorax: a rare complication of fine needle aspiration of the breast. PMID- 2916364 TI - Fine needle aspiration cytology of clinically suspected local recurrences in breast cancer. PMID- 2916365 TI - Radiation-induced cellular changes in the breast: a potential diagnostic pitfall in fine needle aspiration cytology. PMID- 2916366 TI - Squamous cell carcinoma with sarcomatoid variant in the vagina. PMID- 2916367 TI - Nuclear grooves in the aspiration cytology of papillary carcinoma of the thyroid. AB - Nuclear grooving has recently been shown to be a useful morphologic feature in the diagnosis of papillary carcinoma of the thyroid in tissue sections and imprint smears. In order to assess the diagnostic value of nuclear grooving in cytologic specimens, the presence of this feature was evaluated in fine needle aspirates from 20 papillary carcinomas of the thyroid, 10 follicular adenomas, 3 follicular carcinomas, 1 medullary carcinoma, 10 nodular goiters and 4 cases of Hashimoto's thyroiditis. In each case, 30 random high-power fields (HPFs), or all fields in less cellular smears, were examined, and the percentage of the fields in which nuclear grooving could be seen was recorded. Seventeen of 20 papillary carcinomas (85%) showed nuclear grooves in more than 25% of the HPFs examined; in the remaining three cases, grooves were observed in less than 25% of the HPFs. In control cases (all other thyroid lesions), nuclear grooves either were absent or were present in less than 25% of the HPFs examined. These findings suggest that nuclear grooving, when seen in abundance, can be considered a reliable criterion for the diagnosis of papillary carcinoma in fine needle aspiration cytology of the thyroid. The presence of occasional grooves, however, should be regarded as a nonspecific finding. PMID- 2916368 TI - Clinicopathologic management of tumors of the thyroid gland in an endemic goiter area. Combined use of preoperative fine needle aspiration biopsy and intraoperative frozen section. AB - In total, 15,325 fine needle aspiration (FNA) biopsies of the thyroid were examined in the Department of Pathology of the University of Innsbruck, Austria, between 1976 and 1985, with the cytologic results histologically verified in 3,112 cases. Since (1) it is frequently impossible to distinguish benign from malignant encapsulated follicular thyroid tumors by cytologic criteria and (2) there is a high level of follicular thyroid carcinoma in our endemic goiter area, we have adopted a diagnostic strategy that accepts a high percentage of false positive cytologic results in order not to miss highly differentiated follicular carcinoma. To avoid unnecessarily extensive surgical treatment, 1,079 intraoperative frozen section examinations of the thyroid were performed in the same time period in (1) patients with preoperative suspicious or positive FNA cytologic findings, (2) cases with suspicious clinical and anamnestic data and (3) tumors with a suspicious macroscopic appearance without preoperative FNA or with negative or unsatisfactory cytologic findings. In 48 cases (4.5%), the frozen section diagnosis had to be revised after examination of paraffin-embedded tissue. An intraoperative false-positive diagnosis was obtained in 3 cases (0.3%) while a false-negative diagnosis was made in 45 cases (4.2%). The main effort in examining frozen sections should be concentrated on avoiding false-positive errors, which can lead to unnecessary thyroidectomies. PMID- 2916370 TI - Grave's disease. Appearance in cytologic smears from fine needle aspirates of the thyroid gland. AB - The cytomorphologic features were analyzed in thyroid samples obtained by fine needle aspiration (FNA) from 54 cases proven to be Grave's disease (toxic goiter) by a multiparameter study. A fire-flare appearance of the follicular cells and a good cellularity of the smears were the features most frequently observed in these cases. Hurthle cell changes were present in 47% of the cases, and small numbers of lymphocytes were seen in smears from 41% of the cases. Epithelioid cell granulomata and multinucleated giant cells were observed in less than one fourth of the cases. About half of the cases showed some degree of pleomorphism of the follicular cells. Twenty cases of toxic multinodular goiter were similarly analyzed; the features that distinguished this entity from Grave's disease were the absence of epithelioid cells and multinucleated giant cells in the FNA smears. PMID- 2916369 TI - Usefulness of fine needle aspiration of the thyroid in an endemic goiter region. AB - The accuracy of fine needle aspiration (FNA) cytology of the thyroid was addressed in 142 nodular goiters from an endemic goiter region. The aspirations and their interpretation were based on the methodology of the Karolinska Hospital. For practical purposes, the follicular lesions were divided into type I (benign), type II (atypical benign) and type III (suspicious). Excluding the follicular lesions, the cytohistologic agreement for the whole series was 87%, with a correlation of 81.5% for carcinomas. The type I and type II follicular lesions were benign on histologic grounds; 39% of the carcinomas were detected in the type III follicular lesions. The 0.7% false-positive diagnoses increased to 15% when type III follicular lesions were included. No false negatives were recorded. These observations, together with the increase of surgically resected thyroid carcinomas after FNA was accepted as a diagnostic modality, indicate that FNA biopsy of the thyroid is an accurate diagnostic method and is useful in selecting patients for subsequent surgery in areas of endemic goiter. PMID- 2916371 TI - Fine needle aspiration of the thyroid. Distinction between colloid nodules and follicular neoplasms using cell blocks and 21-gauge needles. AB - Although fine needle aspiration (FNA) of the thyroid has been found to be useful in selecting patients for surgery in most cases, the cytologic differentiation of cellular colloid nodules from follicular neoplasms has not been possible because of the scanty amount of tissue obtained by this technique and because of the infrequent preparation of cell blocks, thus precluding appreciation of the tissue architecture. Review of the histology of nodular goiters and follicular neoplasms and comparison of their morphology in smears and cell blocks from FNA specimens with the histology of the surgically excised specimens in 74 cases revealed the presence of hyperplastic papillae and fragments of dilated follicles in the aspirates of most cases of colloid nodules. These two features appear to be specific for colloid nodules and are useful for distinguishing colloid nodules from follicular neoplasms. The merits of using a 21-gauge needle and of preparing cell blocks in thyroid studies are also discussed. PMID- 2916372 TI - Paratesticular adenomatoid tumors. The cytologic presentation in fine needle aspiration biopsies. AB - Adenomatoid tumors are the most common tumors of male paratesticular tissues (epididymis, tunica or spermatic cord) and have also been described in females (uterus, fallopian tube, ovary and paraovarian tissues); fine needle aspiration (FNA) of masses in these locations is increasingly utilized as an alternative to surgical exploration in order to establish a tissue diagnosis. This paper describes the FNA cytodiagnosis of seven cases of paratesticular adenomatoid tumors. The main cytologic criteria included epithelioid sheets and multilayered clusters of monotonous cells with round or ovoid, eccentric nuclei containing small, central nucleoli. Paranuclear clearing with a pink coloration (Giemsa stain) or a clear vacuolelike area (Papanicolaou stain) and abundant cellularity with a background of naked nuclei and stromal fragments were noted. The clinical presentation and clinicohistologic follow-up of these seven cases is also described in detail. A discussion of the differential diagnosis and the expected FNA findings is provided. PMID- 2916373 TI - Retroperitoneal ganglioneuroblastoma. Report of a case diagnosed by fine needle aspiration cytology and electron microscopy. AB - Fine needle aspiration performed on a large retroperitoneal mass in a 12-year-old boy showed neuroblasts in different stages of maturation intermingled with ganglion cells, leading to a cytologic diagnosis of ganglioneuroblastoma. This diagnosis was supported by electron microscopic study of the aspirate, which showed features of neuroblastic differentiation, and by histologic study of the resected tumor. PMID- 2916374 TI - Fine needle aspiration cytology of recurrent ectopic meningioma. AB - Fine needle aspiration was performed on a recurrent extracranial meningioma in the left pterygomaxillary and temporal fossas in a 39-year-old woman. Cytologic and electron microscopic study of the aspirate and comparison to the previously resected specimen proved the recurrent nature of the lesion. The cytologic and ultrastructural findings in meningiomas are discussed with special consideration of the differential diagnosis in extracranial sites. PMID- 2916375 TI - Fine needle aspiration cytology in the management of palpable benign and malignant breast disease. Correlation with clinical and mammographic findings. AB - Two surgeons in a health maintenance organization group practice performed 280 fine needle aspirations (FNAs) on 257 palpable breast lesions in 200 patients. The cytology was interpreted by four pathologists at a community hospital. FNA cytology had a sensitivity of 96% and a specificity of 94% in these cases; there were no false-positive diagnoses of cancer. FNA cytology improved the identification of benign disease and decreased the risk of missing cancers. FNA cytology also improved the predictive value of mammographic information and was more helpful than mammography in demonstrating the need for biopsy of small palpable lesions that turned out to be "minimal" breast cancers. PMID- 2916376 TI - Thyroid function in hyperemesis gravidarum. AB - Plasma total T4 (TT4), T3 (TT3), free T4 (FT4), free T3 (FT3), thyroxine binding globulin, hCG, and erythrocyte zinc content were measured in 43 women with uncomplicated pregnancy and in 71 patients admitted with hyperemesis gravidarum. Plasma concentration of thyroid hormones in hyperemesis subjects showed wide variability and 32% of subjects had high TT4 (higher than mean +2 SD of normal pregnant subjects), 33% had high FT4, 20% had high TT3, and 20% had high FT3. Red cell zinc content, a tissue marker of thyroid status, in the hyperthyroxinemic subjects was not different from that of normothyroxinemic hyperemesis subjects or of subjects with uncomplicated pregnancy. The elevated TT4 concentration decreased spontaneously in all but two of the hyperemesis subjects to normal pregnant levels. The plasma FT4 concentration at presentation correlated with plasma hCG in hyperemesis gravidarum (partial correlation coefficient r = 0.411, P less than 0.01), but not in normal pregnancy (partial correlation coefficient r = 0.043) after allowing for the effect of gestational age. We conclude that approximately one third of hyperemesis subjects show transient hyperthyroxinemia and suggest that hCG or a molecular variant of hCG may stimulate the thyroid gland. PMID- 2916377 TI - Measurement of plasma free and total growth hormone concentrations in patients with growth hormone antibodies developed in response to therapy. AB - Recombinant human growth hormone is more antigenic than pituitary preparations. Since GH antibodies interfere with radioimmunoassay of GH, we measured plasma free and total GH in patients with pituitary dwarfism with GH antibodies during treatment with a recombinant methionyl GH preparation. Plasma free GH was measured in the supernatant after polyethylene glycol precipitation. Total GH was measured after extracting plasma with acid-ethanol. In normal subjects, both free and total GH levels were similar to those measured in plasma by a direct conventional RIA. Peak free GH levels after administration of 4 IU methionyl GH to 3 normal subjects were 38.0, 30.7 and 13.2 micrograms/1, values similar to those measured in most of the patients with GH antibodies. All values were undetectable in one patient with a very high antibody titre. Total GH levels were similar to free GH levels in normal subjects. In patients with GH antibodies, total GH levels were high compared with their free levels, but similar to those assayed by conventional RIA. The patient with the highest antibody titre had total GH levels which were the lowest of those observed in the patients with GH antibodies in spite of having the highest GH levels measured by conventional RIA. The antibody in this particular case may have a high capacity and a high affinity. A relatively poor growth rate in this patient may be associated with the finding of undetectable free GH levels. Measurement of plasma free and total GH may be of value in examining GH dynamics and their relation to the clinical effectiveness of GH treatment in patients with GH antibodies. PMID- 2916378 TI - Inhibition of binding of gonadal steroids to serum binding proteins by non esterified fatty acids: the influence of chain length and degree of unsaturation. AB - The effect of non-esterified fatty acids (NEFA) on the in vitro binding of testosterone, 5-alpha dihydrotestosterone and estradiol E2 to sex hormone binding globulin (SHBG) was examined using pooled normal female serum, and SHBG and albumin fractions obtained from the partial purification of late pregnancy serum. A range of saturated and unsaturated fatty acids were examined for their effect on steroid-protein binding. In normal female serum, NEFA added at physiological concentrations disrupted steroid-protein binding. The shorter chain (C8-C12) saturated acids and the poly-unsaturated acids proved to be more effective inhibitors than the longer chain saturated or mono-unsaturated acids. The greatest inhibition was obtained with E2 whereas the binding of dihydrotestosterone was least affected. With partially purified SHBG, the same concentrations of NEFA were less effective at inhibiting the binding of dihydrotestosterone and testosterone but elicited the same effect with E2. The binding of steroids to albumin appeared to be unaffected by these concentrations of NEFA. PMID- 2916379 TI - Increases in testosterone secretion in adult rams with immunoneutralization of endogenous estradiol occur in the absence of increases in pulsatile LH release or testicular LH receptors. AB - The testes of the ram become more responsive to LH stimulation following immunoneutralization of endogenous estradiol. The possibility that testosterone secretion is facilitated by increased LH-binding activity in the testes was investigated in the present study conducted with adult Dorset X Leicester X Suffolk rams during the time of testicular recrudescence. Patterns of episodic LH release and testosterone secretion (days--5, 10 and 24) and LH-binding activity in testicular biopsy samples (days--1, 14 and 28) were assessed on the days indicated relative to the onset of passive immunization and the establishment of relatively low titres (approximately 1:200) of estradiol antiserum. During the experimental period, mean serum testosterone concentration increased by approximately 150% for the immunized rams as basal concentration and pulse amplitude increased, while all characteristics of testosterone secretion remained unchanged for the nonimmunized rams. Characteristics of LH release and the concentration of LH-binding sites in the testes, however, were always similar for both groups of rams. Further, group differences in FSH and PRL secretion and in the concentration of testicular FSH-binding sites did not occur. These results provide evidence for an estradiol direct (gonadotropin independent) negative feedback component in the regulation of Leydig cell function in the ram. PMID- 2916380 TI - Continuous subcutaneous octreotide infusion markedly suppresses IGF-I levels whilst only partially suppressing GH secretion in diabetics with retinopathy. AB - The response to GH releasing hormone (GHRH 1-29) and 24-h serum GH and IGF-I levels were measured in 9 insulin-dependent diabetics with retinopathy and 6 normal volunteers before and after different treatment regimens with octreotide, a long-acting somatostatin analogue. Octreotide, 50 micrograms by sc injection, completely suppressed GHRH-stimulated GH release in both groups. Thrice daily sc injections for up to 20 weeks were associated with variable plasma octreotide levels and failed completely to suppress GH secretion in either the patients or the normal controls. Three days of continuous sc pump infusion (500 micrograms/24 h) resulted in consistently high plasma octreotide levels and completely suppressed 24-h GH in 4 normal subjects, whilst treatment for up to 16 weeks only partially suppressed GH levels in 6 patients (AUC mU.l-1.h-1; 209 +/- 81 vs 121 +/- 82; P = 0.01). Mean +/- SD IGF-I levels (micrograms/l) in the patients (but not controls) were suppressed into the hypopituitary range by median 6 weeks (range 2-16) pump administration (203 +/- 62 vs 60 +/- 25; P = 0.02). Pump treatment achieved total GH suppression in normal subjects; diabetics with retinopathy seem more resistant to the GH suppressing effects of the drug. However, the reduction of serum IGF-I with prolonged treatment may be of clinical value in arresting the progress of diabetic retinopathy. PMID- 2916381 TI - Serum calcitonin levels in anesthetized rats. AB - In order to determine whether a short period of general anesthesia influences the levels of serum calcitonin (CTs) and whole blood ionized Ca2+ and pH, 10 rats were sequentially anesthetized at 5-day intervals by halothane, ether, or CO2/O2, respectively, and retroorbital blood samples were collected during anesthesia. We noticed significant differences of serum calcitonin but the role of the anesthetics remains unclear, since other factors also could have accounted for the observed variations. Blood pH was strongly decreased by CO2/O2. Whole blood ionized calcium exhibited marked changes, but no correlation was found between whole blood ionized calcium and serum calcitonin. PMID- 2916382 TI - Resistant hyperthyroidism induced by sodium iopodate used as treatment for Graves' disease. AB - Sodium iopodate has recently been advocated for long-term control of hyperthyroidism in Graves' disease. Its advantages over conventional therapy are a rapid fall in thyroid hormones and control of symptoms with a simple dosage regime. We report a case in which severe resistant hyperthyroidism developed during treatment of Graves' disease with sodium iopodate. Sodium iopodate may not be suitable for long-term use in all patients with Graves' disease. PMID- 2916383 TI - Presence of androgen receptors in the hen hypothalamus and pituitary. AB - Soluble and insoluble fractions in a hypotonic buffer solution of hypothalamic preoptic and median eminence areas, and of the anterior pituitary of the hen were found to contain a specific androgen binding component having the properties of a receptor. Administration of testosterone in vivo caused a marked decrease in specific [3H]R1881 (a synthetic androgen) bindings in the soluble fraction with a concomitant increase in the bindings in the insoluble fraction, whereas the sum of the bindings did not change. A similar relationship between the bindings of the two fractions was also observed during an ovulatory cycle. The results may provide an evidence for a direct action of androgens on the hen hypothalamus and pituitary. PMID- 2916384 TI - Enzyme-immunoassay for estrogen receptors in human pituitary adenomas. AB - We have performed an enzyme-immunoassay for estrogen receptor on 56 human pituitary adenomas and compared the results with a single point estradiol binding assay. There was a significant positive correlation between the two assays of cytoplasmic estrogen receptor (r = 0.960). Normal human pituitaries (N = 2) had an estrogen receptor concentration of 17 fmol/mg protein by enzyme-immunoassay. Of 14 prolactinomas, 6 (43%) contained estrogen receptor with a concentration of 33.5 +/- 7.4 (mean +/- SEM) fmol/mg protein. Six of 11 (55%) macroprolactinomas were estrogen receptor-positive, whereas all 3 microprolactinomas were estrogen receptor-negative. Only one (13%) of 8 GH- and PRL-secreting adenomas, and 3 of 6 (50%) gonadotropin-secreting adenomas were estrogen receptor-positive; the latter had a concentration of 13.5 +/- 1.6 fmol/mg protein. Estrogen receptor was not detected in 21 pure GH-secreting adenomas and 7 nonsecreting adenomas. These results demonstrate the precise frequency of estrogen receptor in various human pituitary adenomas, since enzyme-immunoassay as well as single point estradiol binding assay could detect estrogen receptor even in small specimens. Enzyme immunoassay is suitable for evaluation of estrogen receptor status in human pituitary adenomas. PMID- 2916385 TI - Immunoreactive oxytocin and vasopressin in the non-pregnant human uterus and oviductal isthmus. AB - The regional distribution of immunoreactive OT and AVP in the human uterus was investigated. Specimens of non-pregnant human uterus and oviduct were homogenized and extracted. The tissue levels exceeded the plasma concentrations of the peptides. The largest quantities of both peptides were found in the cervix and oviductal isthmus. The amounts found in the uterine fundus and isthmus were, however, not significantly different. Only 23% of immunoreactive OT eluted in the position of standard peptide on high-performance liquid chromatography. All immunoreactive AVP eluted with standard AVP after additional ether extraction of octadecasilyl extracts. We conclude that the human uterus contains materials immunologically and chromatographically identical to oxytocin and vasopressin. PMID- 2916386 TI - Effects of gastrin-releasing peptide on basal and stimulated thyroid hormone secretion in the mouse. AB - Recently, gastrin releasing peptide (GRP) was demonstrated to occur within normal thyroidal C cells. In the present study, the effects of GRP on basal and stimulated thyroid hormone secretion were investigated in the mouse according to the McKenzie technique. Iodine-deficient mice were pretreated with 125I and thyroxine. GRP was found dose-dependently to increase the basal radioiodine levels after iv injection, reflecting a stimulation of basal thyroid hormone secretion. The effect was maximal at a dose level of 3.0 nmol/animal, and at 2 h after injection, when GRP had increased blood radioiodine levels to 152 +/- 8% compared with 96 +/- 5% in controls (P less than 0.001). GRP seemed to exert additive effects on thyroid hormone secretion with vasoactive intestinal peptide and with TSH at a threshold dose level. In contrast, GRP did not influence the stimulatory effects of either a half-maximal dose level of TSH or noradrenaline. Furthermore, neither L-propranolol nor methylatropine influenced the GRP-induced thyroid hormone secretion. It is concluded that GRP has the capacity to stimulate basal thyroid hormone secretion in the mouse. PMID- 2916387 TI - Individual predictability of repeated spinal anaesthesia with isobaric bupivacaine. AB - To evaluate the individual predictability of the spread of spinal anaesthesia, an analysis of 38 patients who had had at least two spinal blocks within 4 years was performed. All spinal blocks were done with the patients in the lateral position at the midline in the interspace LIII-IV, injecting 3 ml of isobaric 0.5% bupivacaine. Regression analysis showed that the predictability of the maximal analgesic spread of the second anaesthesia from the first anaesthesia was highly significant (P less than 0.0001). Therefore, if a higher or lower level of the block is required, another method for the forthcoming anaesthesia may be needed. The reasons for this phenomenon could not be clarified in this retrospective study. PMID- 2916388 TI - Cerebral blood flow and metabolism during adenosine-induced hypotension in patients undergoing cerebral aneurysm surgery. AB - The effects of adenosine-induced hypotension on cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), and cerebral lactate production, together with systemic haemodynamics, were studied in 10 patients undergoing cerebral aneurysm surgery in neurolept anaesthesia with controlled hyperventilation. CBF changes were determined in six of the patients with a retrograde thermodilution technique in the jugular vein. Hypotension was induced with a continuous infusion of adenosine in the superior vena cava. The dose range was 0.06-0.35 mg/kg/min, and this caused a 42% reduction in mean arterial blood pressure (MABP) from 79 +/- 4 to 46 +/- 1 mmHg (10.5 +/- 0.5 to 6.1 +/- 0.1 kPa) through a profound reduction in systemic vascular resistance (SVR), which amounted to 61%. No significant change occurred in CBF. Whole body AV-difference of oxygen was decreased by 37%, and cerebral AV-difference by 28%, corresponding to reductions in whole body oxygen uptake and CMRO2 of 16 and 17%, respectively. Cerebral AV-difference of lactate did not change. In the posthypotensive period MABP was increased by 10%, together with a minor increase in CBF (15%). It is concluded, that adenosine-induced hypotension at MABP levels between 40-50 mmHg (5.3-6.7 kPa) does not affect cerebral oxygenation unfavourably, and may even offer a protective effect by reducing cerebral oxygen demand. The slight CBF increase in the posthypotensive period was probably secondary to an increase in MABP together with a blunted autoregulation, but in no case was this effect considered to be harmful for the patient. PMID- 2916389 TI - Right ventricular dysfunction in septic shock: assessment by measurements of right ventricular ejection fraction using the thermodilution technique. AB - Right ventricular ejection fraction (RVEF) was measured by the thermodilution technique in a series of 127 consecutive critically ill patients monitored with a modified pulmonary artery (PA) catheter equipped with a fast response thermistor. Thermodilution RVEF was significantly lower in septic shock (23.8 +/- 8.2%, 93 measurements) than in sepsis without shock (30.3 +/- 10.1%, 118 measurements) or in the absence of sepsis or cardiopulmonary impairment (32.5 +/- 7.1%, 62 measurements). Both myocardial depression and pulmonary hypertension could account for this impairment of RV function. RVEF decreased from 35.1 +/- 9.8 to 24.2 +/- 10.4% (P less than 0.01) during development of septic shock and increased from 25.0 +/- 7.6 to 29.8 +/- 8.5% (P less than 0.05) during recovery (14 patients). Initial RVEF in septic shock was 27.8 +/- 8.6% in 11 patients who survived but only 20.9 +/- 6.7% (P less than 0.02) in the 23 patients who eventually died. Thus, RV dysfunction is common during septic shock, is directly related to its severity, and can easily be recognized in patients monitored with a PA catheter. PMID- 2916390 TI - Survival compared to the general population and changes in health status among intensive care patients. AB - In order to evaluate intensive care, all adult patients (980) admitted to a multidisciplinary intensive care unit (ICU) during 1 year were followed prospectively. The ICU mortality was 9.6%. One year after admission the survival was 73.6%. By that time the surviving patients had a further survival that was 96% of that of the general population. Of the 1-year survivors, 22.3% had deteriorated in health status compared to 3 months before the stay in ICU. In the admission groups with high mortality the survivors had a more pronounced deterioration in health status. Increased age and length of stay in the ICU were associated with higher mortality but not with changes in health status. We conclude that the outcome of intensive care can be evaluated by studying only the survival, since the survival rate is correlated to changes in health status among survivors in the different admission groups. One year after admission most of the surviving patients had regained their previous health status and their further survival was almost the same as that of the general population. PMID- 2916391 TI - Rebreathing, resistance and external work of breathing in three different coaxial Mapleson D systems. AB - Using a lung model, rebreathing characteristics, resistance against gas flow and the external work of breathing were tested in three different coaxial Mapleson D systems: the Medicvent D system, the Bain original system and the Coax-II system. The rebreathing characteristics were found to be similar in all systems in both spontaneous and controlled ventilation. The Bain system was found to have the lowest resistance and work of breathing and the Coax-II system the highest. The differences were small and clinically insignificant. Both the resistance and the work of breathing increased with fresh gas flow. The resistance against expiration was found to be in the range 135-160 Pa at a total gas flow of 31 1.min-1, which is well within the acceptable level. The resulting end-expiratory pressure was never above 100 Pa (1 cmH2O) in any system. We concluded that there was no clinically significant difference among the three systems despite differences in design. The coaxial Mapleson D systems can also be used safely with high fresh gas flows with regard to resistance and end-expiratory pressures. PMID- 2916392 TI - Continuous interscalene brachial plexus block: clinical efficacy, technical problems and bupivacaine plasma concentrations. AB - Continuous interscalene brachial plexus block with a single dose of 0.5% bupivacaine 1.25 mg/kg, continued with an infusion of 0.25% bupivacaine 0.25 mg/kg/h, was performed on 24 patients to provide analgesia during shoulder surgery and in the postoperative period. The drugs for general anaesthesia included glycopyrrolate, thiopentone, vecuronium, enflurane and N2O/O2. All patients had signs of regional analgesia 30 min after the block without haemodynamic problems. The infusion of local anaesthetic was interrupted in six patients because of a failure in catheter function. Of the remaining 18 patients, nine needed no complementary analgesics and nine patients received, on average, 1.6 doses of oxycodone (0.15 mg/kg/dose) during a 24-h period. Displacement of the interscalene catheters could be prevented by a fixation suture to the skin. Two patients noted a metallic taste during the bupivacaine infusion. The most common complaints were numbness of the hand (n = 15) and hoarseness (n = 5). The mean (+/- s.e.mean) plasma concentrations of bupivacaine at 30, 60, 180 min and 24 h were 0.68 +/- 0.06, 0.62 +/- 0.05, 0.52 +/- 0.04 and 0.76 +/- 0.01 micrograms/ml, respectively. During the 24-h period, the alpha 1-acid glycoprotein (AAG) concentration (mean +/- s.e.mean) in plasma rose from 0.41 +/- 0.04 g/l to 0.54 +/- 0.04 g/l (P less than 0.001). The concentration of free bupivacaine was below detectable levels (less than 0.01 micrograms/ml) after the 24-h infusion. The rise in AAG probably increases binding of bupivacaine to plasma proteins, diminishing the risk of systemic toxicity. PMID- 2916394 TI - Gradient echoes: simplified. PMID- 2916393 TI - Low-flow anaesthesia does not increase the risk of microbial contamination through the circle absorber system. AB - In the circle absorber system, a decrease in fresh gas flow means a higher degree of rebreathing, and, consequently, a higher temperature and humidity within the system. With our present hygienic routines, the circle system tubings are changed and decontaminated once daily. Thus, the same circle system is used for several patients each day. In order to evaluate whether the risk of bacterial contamination increased with the introduction of low-flow anaesthesia, 122 patients anaesthetized with either a low-flow technique (less than 1.5 l fresh gas flow/min) or with medium fresh gas flows (3-6 l/min) were studied. Bacterial samples were taken preoperatively from the oropharynx and postoperatively from five locations in the circle system. The patients were studied postoperatively for signs of respiratory tract infection. There were few positive bacteria cultures from the tubings in the circle system, regardless of fresh gas flow. No pathogens were found in the inspiratory tubings and no cases of postoperative respiratory tract infection could be related to bacterial spread from the anaesthesia machine. There were no indications that the present hygienic management was insufficient for the medium- or the low-flow circle system techniques. PMID- 2916395 TI - Acrodermatitis enteropathica. AB - Acrodermatitis enteropathica results from a defect in zinc metabolism inherited as an autosomal recessive trait. Zinc is chelated in the gastrointestinal tract by an oligopeptide that is normally destroyed in the bowel. Zinc deficiency results in skin and bowel lesions, as well as alterations in mental status. If the disorder is not treated, death occurs from infection and/or marasmus. Blood zinc levels confirm the diagnosis. Dramatic recovery and normal development occur when dietary zinc is supplemented. PMID- 2916396 TI - Trichomonas infections in men. AB - Trichomonas vaginalis, a common pathogen in the female genital tract, produces a characteristic clinical picture in women. Less well recognized are the manifestations of Trichomonas infestations of the male genital tract, which include urethritis and chronic prostatitis. Multiple-glass urinalysis and selective use of Trichomonas cultures may improve recognition of this organism in the family practice setting. PMID- 2916397 TI - Chronic compartment syndrome. AB - Chronic compartment syndrome typically affects young people who are engaged in endurance sports. The primary clinical feature is a sensation of tightness or aching pain in a defined compartment of the affected limb, starting during activity or hours after activity ceases and lasting for varying lengths of time. The diagnosis is based on the history and on measurement of compartmental pressures. Fasciotomy or partial fasciectomy is the definitive treatment. PMID- 2916398 TI - Virus clearance in HIV-infected patients. PMID- 2916399 TI - Interferon alfa for Kaposi's sarcoma in early AIDS. PMID- 2916400 TI - Cool ultrasonic humidifiers for lowering fever. PMID- 2916401 TI - Pediatric urinary tract infections. PMID- 2916402 TI - The future of family practice. PMID- 2916403 TI - Assessment of myocardial infarct size by means of T2-weighted 1H nuclear magnetic resonance imaging. AB - Proton (1H) nuclear magnetic resonance (NMR) imaging is thought to depict zones of recent myocardial infarction in contrast to noninfarcted myocardium. This is related to T2 increases in infarct zones that have been verified previously by relaxometry measurements in excised myocardial samples. Accordingly the present study was undertaken to evaluate a 1H NMR imaging method to optimize T2 contrast and measure infarct size in a high-field imaging system (1.5 T). To accomplish this, NMR images were acquired every other R wave with echo times of 30 and 100 msec. The first echo image was used for myocardial border definition and the second echo image, which highlighted the myocardial infarction, for infarct border definition. This T2-weighted approach yielded a significant correlation between infarct size by NMR and pathologic methods. However, NMR imaging tended to overestimate infarct size, and the NMR image depicted abnormal signal well beyond the extent of the pathology-determined infarct. There was a significant relationship between NMR-imaged infarct size and myocardial mass with microsphere determined reduction in blood flow of 25% or more. These data suggest that T2 weighted NMR imaging depicts not only infarct but also some reversibly injured myocardium. PMID- 2916404 TI - Coronary collateral circulation: clinical significance and influence on survival in patients with coronary artery occlusion. AB - In a consecutive series of 96 patients with coronary artery occlusion, 67 had good and 29 had no or poor collateral circulation. Patients with good collaterals had the severest degree of coronary artery disease. Good collaterals are associated with a higher incidence of angina pectoris and normal electrocardiogram and with lower incidence of Q-waves, positive exercise tests, heart failure, previous myocardial infarction, and dyskinesia at ventriculography. Survival rates after 10 years were (1) 51.5% with good and 34.5% with poor collaterals (p less than 0.1), (2) 59.4% with angina pectoris and good collaterals and 41.2% with angina pectoris and poor collaterals (p less than 0.05), (3) 64.8% without and 24.4% with heart failure and good collaterals (p less than 0.001), and (4) 58.3% without and 16.1% with heart failure and poor collaterals (p less than 0.01). Good collaterals protect the myocardium by prevention of acute myocardial infarction and heart failure and thus improve survival. PMID- 2916405 TI - The dynamics of progression of coronary atherosclerosis studied in 168 medically treated patients who underwent coronary arteriography three times. AB - To study the dynamics of progression of coronary atherosclerosis we analyzed findings in 168 patients who underwent coronary arteriography three times without undergoing coronary surgery or percutaneous transluminal coronary angioplasty. Of 66 patients who had progression in interval 1 (from first to second coronary arteriogram), 32 also had progression in interval 2 (from second to third coronary arteriogram); of 102 patients who had no progression in interval 1, 37 had progression in interval 2. In only 9 of the 32 patients who had progression during both intervals was the same lesion involved, and in six of these patients other lesions were also involved. Progression correlated with the duration of the interval between catheterizations, an increase in symptoms, and the occurrence of myocardial infarction. Analysis of variance showed no significant differences in mean values for age, blood pressure, total serum cholesterol, and serum triglycerides in the four main progression groups. Progression of coronary atherosclerosis is a highly unpredictable process. It follows a nonlinear course, and information derived from sequential coronary arteriograms is of little value in predicting future progression. PMID- 2916406 TI - Role of resting thallium201 perfusion in predicting coronary anatomy, left ventricular wall motion, and hospital outcome in unstable angina pectoris. AB - We performed quantitative thallium scintigraphy in 66 unstable angina patients, 5.6 +/- 5.1 hours after rest pain, to predict coronary anatomy, left ventricular wall motion, and hospital outcome. Thallium defects and/or washout abnormalities were present in 5 of 10 (50%) patients with coronary stenoses less than 50%, 27 of 33 (82%) patients with coronary stenosis greater than or equal to 50% and no history of previous myocardial infarction, and in 23 of 23 patients (100%) with histories of previous infarction. Defects were uncommon in the territory of vessels with less than 50% (13 of 61, 21%), but significantly more common in the territory of vessels with greater than or equal to 50% stenosis (57 of 137, 42%), p less than 0.005. With the addition of washout abnormalities to defect analysis, sensitivity for detection of coronary stenoses improved to 67% (92 of 137), p less than or equal to 0.005, but specificity fell to 59% (36 of 61), p less than 0.01. Segmental wall motion abnormalities were less common in segments with normal perfusion (21%) or in those with washout abnormalities alone (19%), than in segments with thallium defects (45%, p less than 0.005). Defects in patients with previous infarction were common in both segments, with normal (26 of 66, 40%) or abnormal (24 of 45, 53%) wall motion. Eleven of 18 patients with in hospital cardiac events, but no history of myocardial infarction, had resting thallium defects, whereas only 8 of 25 patients without cardiac event had thallium defect (p = 0.056).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2916407 TI - Different coronary vasomotor effects of nifedipine and therapeutic correlates in angina with spontaneous and effort components versus Prinzmetal angina. AB - Flow impedance, probably of vasomotor origin, superimposed on severe coronary stenosis has been considered a trigger for the spontaneous component of angina occurring both on effort and at rest. To investigate more thoroughly this pathophysiologic aspect we evaluated (by means of quantitative coronary angiography) the acute vasomotor reaction to nifedipine (10 mg sublingually) of significant (greater than 50%) stenotic lesions in 22 patients with double component angina. We also correlated this reaction with the clinical response (daily number of ischemic episodes evaluated by means of 48-hour Holter ambulatory monitoring) to treatment with nifedipine (20 mg four times a day); calcium channel blockade, in fact, is considered a specific remedy in cases of altered coronary vasomotility. Patients with Prinzmetal angina, who were known to have homogeneous coronary vasodilating reactions and favorable clinical responses to nifedipine, were studied by means of the same methods and served as the control group (14 patients). In double-component angina the residual lumen diameter of significant lesions was unchanged in two patients, enhanced in 10, and reduced in 10 after sublingual nifedipine; lumen variations from baseline values ranged from +1.29 to -1.56 mm. Acute changes in stenosis correlated closely with results obtained with oral treatment. In the group with Prinzmetal angina, coronary stenoses invariably responded with dilatation (the residual coronary lumen increased by an average of 69% of baseline); 100% of the patients in this group responded favorably to treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2916408 TI - Dose- and time-related vasodilator response of conduit coronary arteries to intracoronary isosorbide dinitrate in human beings. AB - The time course of the vasodilation of different segments of the epicardial coronary vasculature after three different doses of intracoronary isosorbide dinitrate (ISDN) was investigated in angiographically normal coronary arteries in 10 patients with quantitative coronary angiography. In five patients, 0.1 mg and 0.3 mg ISDN were injected intracoronary 30 minutes apart, and the effect of each dose was assessed at 1, 5, 10, and 15 minutes after the administration by serial angiograms. In five additional patients, a single dose of 3 mg was injected and coronary vasodilation was assessed at 1, 5, 10, 15, and 20 minutes. After each dose, dilation of epicardial coronary arteries occurred within 1 minute, peaked at 5 minutes and progressively decreased thereafter. Relative to control, peak percent diameter increase was (mean +/- SEM) 10% +/- 0.9% (p less than 0.01), 18.5% +/- 1.5% (p less than 0.01), and 26% +/- 2.1% (p less than 0.01) after 0.1, 0.3, and 3.0 mg, respectively. When small (1 to 2 mm), medium (2 to 3 mm), and large (greater than 3 mm) vessels were separately analyzed, peak response was respectively 12% +/- 1.3% (p less than 0.01), 9% +/- 1.9% (p less than 0.01), and 7% +/- 1% (p less than 0.05) after 0.1 mg ISDN; 22% +/- 1.8% (p less than 0.01), 16% +/- 1.3% (p less than 0.01), and 12% +/- 0.8% (p less than 0.01) after 0.3 mg; and 38% +/- 2.4% (p less than 0.01), 22% +/- 2.1% (p less than 0.01), and 17% +/- 2% (p less than 0.01) after 3.0 mg. The duration of the response increased with the dose, but was inversely related to the size of the vessel.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2916409 TI - Carbon monoxide and lethal arrhythmias in conscious dogs with a healed myocardial infarction. AB - Environmental studies suggested that exposure to carbon monoxide (CO) increases cardiovascular mortality among patients with coronary artery disease. We investigated whether, in dogs with a healed anterior myocardial infarction at low and high risk for ventricular fibrillation, acute exposure to CO has adverse effects during acute myocardial ischemia combined with exercise. One month after myocardial infarction, 17 dogs had ventricular fibrillation and 16 survived during the combined exercise and ischemia test. These tests were then repeated in all dogs with different concentrations of carboxyhemoglobin (COHb) (from 5% to 15%). With 15% COHb, heart rate (HR) at rest and during exercise was higher (p less than 0.05) than in the control tests. Surprisingly, the reflex HR response to acute ischemia was also altered; namely, the HR reduction characteristic of the low-risk animals was anticipated and accentuated (-31 +/- 25 versus 2 +/- 30 beats/min, p less than 0.05). Conversely, the HR increase characteristic of the high-risk group was reduced by CO (44 +/- 52 versus 72 +/- 43 beats/min, p less than 0.05). With 15% COHb, malignant arrhythmias occurred in two of the low-risk dogs and in none of the high-risk dogs. In the latter, CO was tested with a combination of exercise work load and myocardial ischemia duration not associated with ventricular fibrillation (VF) in the control condition. This study demonstrated that brief exposure to CO (1) profoundly alters the reflex HR response to exercise and to acute myocardial ischemia and (2) does not enhance the occurrence of malignant arrhythmias in conscious dogs with a healed myocardial infarction. PMID- 2916410 TI - Improved internal defibrillation efficacy with a biphasic waveform. AB - Clinically available automatic implantable defibrillators use a monophasic truncated exponential waveform shock; after delivery the charge remaining on the device's capacitors is "dumped" internally and wasted. The efficacy of a monophasic and biphasic truncated exponential defibrillation waveform produced by a single capacitor discharge was compared in seven closed-chest, pentobarbital anesthetized dogs. Defibrillation leads consisted of a new deployable intrapericardial electrode system. The monophasic waveform was positive and 6 msec in duration. The biphasic waveform had a positive phase identical to that of the monophasic waveform and a negative phase of equal duration with its initial voltage equal to 50% of the final voltage of the positive phase. Defibrillation shocks of varying initial voltage were delivered to construct curves of the percentage of successful defibrillation versus initial voltage and delivered energy, and the voltage and energy required for 50% (V50 and E50, respectively) and 80% (V80 and E80, respectively) success were compared. The biphasic waveform had significantly lower initial voltage (V50: 194 +/- 48 volts vs 227 +/- 48 volts, p less than 0.001; V80: 217 +/- 55 volts vs 256 +/- 66 volts, p less than 0.02) and energy (E50: 2.7 +/- 1.3 joules vs 3.4 +/- 1.5 joules, p less than 0.01; E80: 3.4 +/- 1.6 joules vs 4.3 +/- 2.2 joules, p less than 0.05) requirements than the monophasic waveform. It is concluded that a biphasic waveform produced by a single discharge that uses the "free" energy remaining on the capacitors significantly reduces the initial voltage and energy requirements for successful defibrillation and may improve the efficacy of future automatic implantable defibrillators. PMID- 2916411 TI - Detection of experimental myocarditis by monoclonal antimyosin antibody, Fab fragment. AB - The purpose of this study was to determine whether monoclonal antimyosin Fab (antigen binding fragment) was capable of labeling hearts with experimental coxsackievirus myocarditis, and to determine whether Fab could be used for detecting myocardial damage in either early or chronic phases of the disease. Sixty-five, 3-week-old cesarean-derived 1 (CD 1) mice were divided into two groups: group I (noninfected animals) and group II (infected with coxsackievirus B3). Mice from each group were killed on days 7, 17, 30, or 90 of infection. Forty-eight hours before killing, mice were injected with monoclonal I125 antimyosin, Fab (25 microCi/injection) and radioactivity was counted in the heart. Selected heart sections were also examined by autoradiography. Heart radioactivity, count/m/mg (m +/- SEM) on days 7, 17, 30, and 90 of infection was 10.8 +/- 1.7, 21.3 +/- 1.1, 11.2 +/- 3.4, and 12.4 +/- 1.5 for group I, versus 36.7 +/- 8.0 (p less than 0.01), 50.0 +/- 4.5 (p less than 0.001), 33.4 +/- 16.1 (p = NS), and 40.6 +/- 8.5 (p less than 0.01) for group II, respectively. Autoradiography revealed focal uptake within areas of necrotic myocardium. We conclude that I125 Fab may be useful in detecting myocardial damage in the experimental model of murine myocarditis up to day 90 of infection. PMID- 2916412 TI - Noninvasive assessment of diastolic and systolic properties of ibopamine in patients with congestive heart failure. AB - The acute effect of a single oral 100 mg dose of ibopamine on systolic and diastolic left ventricular function in nine patients with congestive heart failure was assessed by quantitative M-mode and pulsed Doppler echocardiography. Echocardiography was performed at baseline and 30, 60, and 120 minutes after ingestion of drug. Indices of systolic and diastolic left ventricular function were derived from digitized tracings of the septal and posterior endocardial surfaces and transmitral and aortic valve velocity profiles. Ibopamine significantly improved systolic function as reflected by a decrease in the preejection period to left ventricular ejection time ratio from 0.57 +/- 0.16 at baseline to 0.47 +/- 0.15 (p less than 0.05) 30 minutes after ingestion of drug. The maximum improvements in stroke volume and cardiac output after ibopamine were from 63 +/- 35 to 72 +/- 40 ml (p less than 0.05) and 4.6 +/- 1.7 to 5.4 +/- 2.1 L/min (p = 0.05), respectively. The contribution of atrial systole to total diastolic filling increased from 32 +/- 10% at baseline to 37 +/- 12% (p less than 0.05) after 30 minutes and persisted for at least 120 minutes. The distribution of diastolic filling was significantly altered after ingestion of ibopamine as reflected by a decrease in the ratio of the time-velocity integrals of left ventricular filling during early diastole and atrial systole (Ei/Ai) from 2.44 +/- 1.08 at baseline to 1.98 +/- 0.97 (p less than 0.05) 30 minutes after drug. The decrease in the Ei/Ai persisted for at least 120 minutes. The duration of the effect of ibopamine on diastolic filling persisted longer than its effect on augmenting systolic function. The positive effect of ibopamine on systolic function makes it a promising drug in the treatment of congestive heart failure. PMID- 2916413 TI - Calculation of transmitral flow by Doppler echocardiography: a comparison of methods in a canine model. AB - Although several Doppler echocardiographic methods for measuring transmitral flow have been described, the optimal method for calculation of flow remains unclear. Seven time/shape combinations were tested in an experimental preparation in which mitral flow could be precisely controlled and measured. Annular shape was considered to be either circular or elliptical, and the mitral orifice area was calculated from the anteroposterior and/or the mediolateral dimension(s) recorded at early and middiastole. In addition the orifice area was calculated from the maximal mitral leaflet area corrected for diastolic variation. Transmitral flow ranged between 0.4 and 4.6 L/min. Good correlations with measured transmitral flow (r = 0.83 to 0.92) were observed for all methods of calculating the mitral orifice area. Methods that assumed a circular geometry and used the mediolateral annular diameter overestimated flow. Conversely, flows calculated by means of the anteroposterior diameter with the assumption of a circular anulus underestimated flow. The best approximations of transmitral flow were obtained with the assumption of an elliptical configuration that used measurements made in early diastole (Y = 1.04x + 0.2) and with the Fisher method (y = 0.94x + 0.08). Thus in the canine model approximation of the mitral orifice as an ellipse provides the most accurate measurement of transmitral flow. PMID- 2916414 TI - Analysis of the early rise in aortic transvalvular gradient after aortic valvuloplasty. AB - The relationship between dynamic changes in aortic valve gradient and left ventricular ejection performance in the early period after successful percutaneous aortic valvuloplasty has not been described in detail. Accordingly 20 adult patients with severe symptomatic calcific aortic stenosis underwent first-pass radionuclide angiography and Doppler echocardiography before, immediately after, and 2 to 4 days after the valvuloplasty procedure. A significant (p less than 0.001) reduction in peak-to-peak (72 +/- 24 mm Hg to 36 +/- 11 mmHg) and mean (60 +/- 20 mm Hg to 34 +/- 9 mm Hg) transaortic gradient and an increase in aortic valve area (0.5 +/- 0.2 cm2 to 0.8 +/- 0.2 cm2) were measured by high-fidelity micromanometer catheters immediately after aortic valvuloplasty. Results of Doppler echocardiography showed a significant (p less than 0.001) immediate decrease in peak instantaneous (81 +/- 22 mm Hg to 53 +/- 15 mm Hg) and mean (48 +/- 14 mm Hg to 31 +/- 9 mm Hg) aortic gradients. However, 2 to 4 days later a significant (p less than 0.001) return of peak (56 +/- 15 mm Hg to 65 +/- 20 mm Hg) and mean (31 +/- 9 mm Hg to 39 +/- 12 mm Hg) transvalvular gradient occurred. Aortic valve area as determined by the continuity equation also increased from 0.4 +/- 0.2 cm2 to 0.6 +/- 0.2 cm2 immediately after the procedure (p less than 0.001), then partially returned to baseline (0.5 +/- 0.2 cm2; p less than 0.005) at 2 to 4 days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2916415 TI - Quantification of left ventricular myocardial mass in humans by nuclear magnetic resonance imaging. AB - The ability of NMRI to assess LV mass was studied in 20 normal males. By means of a 1.5 Tesla GE superconducting magnet and a standard spin-echo pulse sequence, multiple gated short-axis and axial slices of the entire left ventricle were obtained. LV mass was determined by Simpson's rule with the use of a previous experimentally validated method. The weight of the LV apex (subject to partial volume effect in the short-axis images) was derived from axial slices and that of the remaining left ventricle from short-axis slices. The weight of each slice was calculated by multiplying the planimetered surface area of the LV myocardium by slice thickness and by myocardial specific gravity (1.05). Mean +/- standard deviation of LV mass and LV mass index were 146 +/- 23.1 gm (range 92.3 to 190.4 gm) and 78.4 +/- 7.8 gm/m2 (range 57.7 to 89.4 gm/m2), respectively. Interobserver agreement as assessed by ICC was high for determining 161 individual slice masses (ICC = 0.99) and for total LV mass (ICC = 0.97). Intraobserver agreement for total LV mass was also high (ICC = 0.96). NMRI determined LV mass correlated with body surface area: LV mass = 55 + 108 body surface area, r = 0.83; with body weight: LV mass = 26 + 0.77 body weight, r = 0.82; and with body height: LV mass = 262 +/- 5.9 body height, r = 0.75. Normal limits were developed for these relationships. NMRI-determined LV mass as related to body weight was in agreement with normal limits derived from autopsy literature data.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2916416 TI - Detection of apical hypertrophic cardiomyopathy by magnetic resonance imaging. PMID- 2916417 TI - Improved visualization of discrete subvalvular aortic stenosis by transesophageal color-coded Doppler echocardiography. PMID- 2916418 TI - Hypereosinophilic syndrome resulting in aortic and mitral stenosis: a case requiring double valve replacement. PMID- 2916419 TI - Magnetic resonance imaging of vascular conduits in coarctation of the aorta. PMID- 2916420 TI - Interruption of aortic regurgitation by the intimal flap of an aortic dissection: Doppler echocardiographic observations. PMID- 2916421 TI - Percutaneous balloon valvuloplasty for tricuspid stenosis: hemodynamic and pathological findings. PMID- 2916422 TI - Oxygen uptake and heart rate during cross-country skiing and track walking after myocardial infarction. PMID- 2916423 TI - Propafenone and 5-hydroxypropafenone concentrations in the right atrium of patients undergoing heart surgery. PMID- 2916424 TI - Defibrillation threshold testing: necessary but evil? PMID- 2916425 TI - Exercise testing in angina pectoris: the importance of protocol design in clinical trials. PMID- 2916426 TI - Regional and global biventricular function during dipyridamole stress testing. AB - This study assesses the relation between regional ventricular performance (using 2-dimensional echocardiography) and global systolic and diastolic indexes of biventricular myocardial function (using hemodynamic monitoring) during dipyridamole stress testing. Simultaneous 2-dimensional echocardiographic and biventricular hemodynamic monitoring during dipyridamole infusion (0.56 mg/kg over 4 minutes) was performed in 19 patients. All patients had a normal resting function. Eleven of the 19 patients had a positive echocardiography test (new wall motion dyssynergy with dipyridamole) and they formed group 1. Eight patients had a negative echocardiography test (group 2). During baseline conditions, no significant differences were found in the 2 groups: rate pressure product (107 +/ 16 vs 108 +/- 13 mm Hg x beats/min x 1/100), positive left ventricular (LV) dP/dt (1,950 +/- 473 vs 2,262 +/- 430 mm Hg/s), negative LV dP/dt (-2,069 +/- 620 vs -2,205 +/- 245), LV end-diastolic pressure (8.2 +/- 4.4 vs 9.6 +/- 4.0 mm Hg), right ventricular positive dP/dt (368 +/- 133 vs 400 +/- 190 mm Hg/s) and negative dP/dt (-281 +/- 89 vs -383 +/- 147). At peak dipyridamole, the 2 groups were different for LV end-diastolic pressure (20 +/- 10 vs 8 +/- 5 mm Hg, p less than 0.01), LV positive dP/dt (2,100 +/- 688 vs 3,013 +/- 851 mm Hg/s, p less than 0.01) and negative dP/dt (-1,868 +/- 518 vs -2,564 +/- 272, p less than 0.01). At peak ischemia, LV positive dP/dt increased slightly, but not significantly, while negative dP/dt decreased significantly (p less than 0.01) in comparison with resting values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2916427 TI - Evaluation of electrode polarity on defibrillation efficacy. AB - The effect of electrode polarity on defibrillation thresholds in humans is unknown. This prospective, randomized evaluation of electrode polarity on defibrillation thresholds was performed in 21 survivors of ventricular fibrillation (VF) undergoing cardiac surgery. Defibrillation was always performed with 2 identical large rectangular, wire mesh electrodes positioned over the anterior wall of the right ventricle and the posterolateral wall of the left ventricle. The initial electrode polarity for the left ventricular (LV) electrode was chosen randomly for determination of the defibrillation threshold. Subsequently, electrode polarity was reversed. The defibrillation threshold was defined as the lowest pulse amplitude that would effectively terminate VF with a single discharge delivered 10 seconds after initiation of an episode of VF with alternating current. For each defibrillation pulse, voltage, current, resistance and delivered energy were recorded. Of the 21 patients, 15 (71%) had a lower defibrillation threshold when the LV electrode was positive, 2 patients (10%) had a lower defibrillation threshold when the LV electrode was negative and 4 patients (19%) had equal defibrillation thresholds (within 0.5 J) regardless of polarity. The mean leading edge defibrillation threshold voltage was 370 +/- 88 volts when the LV electrode was negative and 320 +/- 109 volts (14% less) when the LV electrode was positive (p = 0.014). Mean leading edge defibrillation threshold current was 9.3 +/- 3.1 amps when the LV electrode was negative compared to 7.7 +/- 3.1 amps (17% less) when the LV electrode was positive (p = 0.0033). There were no differences in resistance with the 2 configurations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2916428 TI - Effect of intravenous propranolol or verapamil on infant orthodromic reciprocating tachycardia. AB - The effects of intravenous verapamil (0.15 mg/kg) and propranolol (0.2 mg/kg) with regard to atrioventricular (AV) conduction and tachycardia termination during paroxysmal atrial tachycardia were compared in 2 groups of infants (verapamil n = 14, propranolol n = 18, mean age 80 +/- 21 days, range 1 to 364). Using transesophageal recording techniques, tachycardia cycle length, AV intervals and ventriculoatrial intervals were measured before and after drug administration. Both intravenous propranolol and verapamil significantly prolonged tachycardia cycle length and AV interval (cycle length--propranolol 230 +/- 30 to 262 +/- 33 ms, p less than 0.05, verapamil 223 +/- 38 to 245 +/- 32 ms, p less than 0.05; AV interval--propranolol 98 +/- 26 to 126 +/- 38 ms, p less than 0.05, verapamil 96 +/- 19 to 109 +/- 24 ms, p less than 0.05). Neither drug prolonged the ventriculoatrial interval. Tachycardia terminated after intravenous verapamil in 11 of 14 infants (79% efficacy rate). Tachycardia terminated in 0 of 18 after intravenous propranolol (0% efficacy rate). In 8 infants an atrial deflection was recorded on the esophageal electrocardiogram at the time of tachycardia termination after intravenous verapamil, which suggested that tachycardia terminated by block occurring in the AV node. In 2 infants a ventricular deflection was recorded at the time of tachycardia termination after verapamil, which suggested that block occurred in the accessory connection. Both drugs prolonged tachycardia cycle length by prolonging AV conduction to a similar degree.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2916429 TI - Use of the automatic external defibrillator in homes of survivors of out-of hospital ventricular fibrillation. AB - This 57-month study evaluated the use of automatic external defibrillators (AEDs) in the homes of high risk cardiac patients (survivors of out-of-hospital ventricular fibrillation [VF]). The goal was to determine the utility of these devices by trained lay persons in actual cardiac arrest episodes. Ninety-seven survivors of out-of-hospital VF were enrolled in the study; 59 patients received AEDs, and 38 patients served as a control group. During the study period, 7 deaths occurred in the hospital without preceding out-of-hospital cardiac arrest or from noncardiac causes. There were 14 out-of-hospital cardiac arrests, 10 in the AED group and 4 in the control group. There was 1 long-term survivor in the control group. In the AED group, among the 10 cardiac arrests for which the device was available, it was used in 6. Only 2 patients were in VF; 1 was resuscitated with residual neurologic deficits and survived several months. This study observed a small potential for AEDs to save high risk patients. PMID- 2916430 TI - Reduction of ventricular arrhythmias by atropine during coronary arteriography. AB - Sustained ventricular arrhythmia is a well-recognized complication of cardiac catheterization, often occurring after selective coronary artery injection of contrast medium. The role of autonomic reflexes in the pathogenesis of this phenomenon is unclear. Although the muscarinic antagonist atropine is often administered prophylactically before coronary angiography to reduce the likelihood of sinus bradycardia and vasovagal reactions, its influence on ventricular arrhythmias in this setting has not been established. This case control trial studied 648 patients undergoing coronary arteriography to investigate this issue. Eleven case subjects (those with ventricular tachyarrhythmia) were identified. Control subjects (those without ventricular tachyarrhythmia) were matched for baseline heart rate (+/- 6 beats/min), age (+/- 10 years), sex and calendar year of procedure using a 1:3 sampling ratio. All 26 potential clinical, anatomic and hemodynamic covariates were statistically similar between groups. Ventricular tachyarrhythmias were more likely to occur after selective right coronary injection (odds ratio 15.1, p = 0.0008) but not after multiple contrast injections (odds ratio 0.918, difference not significant). Most importantly, atropine sulfate was administered prophylactically to 18 of 33 control subjects (55 +/- 9%) but only 1 of 11 cases (9 +/- 9%), generating a significant odds ratio of 12.0 (p = 0.02). Thus, the odds of experiencing sustained ventricular tachyarrhythmias during coronary arteriography may potentially be reduced 12-fold by prior administration of atropine, even in patients with normal baseline heart rates. PMID- 2916431 TI - Relation of exercise capacity to resting arterial oxygen transport in left ventricular dysfunction. AB - To determine the relation between arterial oxygen delivery and exercise capacity, 38 men with mild to severe chronic left ventricular (LV) dysfunction (New York Heart Association functional class II or III) were studied. All diagnostic cardiac catheterizations were performed 1 week before the exercise tests and the mean LV ejection fraction was 0.30 +/- 0.07. All patients performed graded treadmill exercise tests according to the Sheffield protocol. The relation between supine resting hemodynamic measurements did not correlate with exercise duration. Only resting cardiac output (r = 0.54, p less than 0.01) and systemic vascular resistance (r = -0.51, p less than 0.05) correlated weakly with exercise duration. However, arterial oxygen transport was highly related to exercise duration (r = 0.76, p less than 0.001) and peak oxygen consumption (r = 0.71, p less than 0.001). Thus, knowledge of calculated arterial oxygen transport can predict exercise capacity in patients with chronic LV dysfunction. PMID- 2916432 TI - Long-term follow-up of patients with echocardiographically detected mitral anular calcium and comparison with age- and sex-matched control subjects. AB - One hundred seven patients with echocardiographically documented mitral anular calcium (MAC) and 107 age- and sex-matched control subjects without MAC were studied and followed for a mean of 4.4 +/- 2.4 (standard deviation) years. Fourteen (7%) patients were lost to follow-up. Compared with the control group, patients with MAC had higher frequency of precordial murmurs (p less than 0.0001), cardiomegaly (p less than 0.0001), left atrial enlargement (p less than 0.0001), and rhythm and conduction disturbances (p less than 0.0001). During the follow-up, patients with MAC had higher incidence of valve replacement (p less than 0.0025), permanent pacemaker implantation (p less than 0.0025), congestive heart failure (p less than 0.0001), thromboembolic cerebrovascular event (p less than 0.01), sudden death (p less than 0.001) and total cardiac death (p less than 0.0001). However, the frequencies of myocardial infarction, coronary artery bypass surgery and angioplasty, endocarditis or noncardiac death were not significantly different between patients with MAC and the control subjects. Thus, patients with MAC have higher frequencies of precordial murmurs, cardiomegaly, left atrial and ventricular enlargement, rhythm and conduction disturbances. They more frequently undergo valve replacement and permanent pacemaker implantation, develop congestive heart failure and die of cardiac causes than age- and sex matched control subjects. PMID- 2916433 TI - Scanning electron microscopy of surgically excised human mitral valves in patients over 45 years of age. AB - Leaflets were obtained from 23 diseased mitral valves of patients over 45 years of age removed at the time of prosthetic valve insertion and the topography was studied with scanning electron microscopy. The clinical diagnosis in all cases was probable rheumatic heart disease. Filiform processes (Lambl's excrescences) were seen on 15 of 23 (65%) of these leaflets. Some of these processes appeared to develop when either bundles of collagen or elastic fibers in the connective tissue framework of the cusp were broken. The freed portion of the fiber then served as a nidus for thrombus formation. The endothelium on the surface of the leaflets was consistently altered. Endothelial cells were changed in shape, had microvilli scattered over their exterior, showed discontinuous cell borders and were desquamated, either singly or in groups. Elements of the peripheral blood adhered to the exposed subendothelium. Erythrocytes were usually entrapped in fibrin networks. Single activated platelets and platelet aggregates adhered to the fibers of the exposed subendothelial connective tissue. Surface mineral deposits were composed of granular spherulites, which contained both calcium and phosphorous. This study extends our understanding of the architectural modifications that contribute to the continuing pathologic process of rheumatic mitral valve disease. PMID- 2916434 TI - Two-dimensional echocardiographic findings in systemic sarcoidosis. AB - The records of 88 patients with systemic sarcoidosis who underwent 2-dimensional echocardiography were reviewed to define the typical echocardiographic abnormalities in patients with clinical evidence of cardiac involvement. Twelve patients (14%) had echocardiographic evidence of left ventricular systolic dysfunction attributed to cardiac sarcoidosis (segmental hypokinesis in 8 patients and global hypokinesis in 4 patients). A high incidence of congestive heart failure (9 of 12) and conduction system disease (7 of 12) was characteristic of these patients. The remaining 76 patients had normal echocardiograms or abnormalities attributed to nonsarcoid sources. In 8 (11%) of these 76 patients, there were significant clinically unexplained conduction abnormalities likely related to sarcoidosis. PMID- 2916435 TI - Comparison of low osmolality ionic (ioxaglate) versus nonionic (iopamidol) contrast media in cardiac angiography. AB - A double-blind randomized study was performed in 60 patients to compare the electrocardiographic and hemodynamic changes induced during cardiac angiography by 2 contrast media with relatively low osmolality. Ioxaglate meglumine sodium, an ionic dimer contrast medium, was compared with iopamidol, a nonionic compound. Of the 30 patients who received ioxaglate, 13 (43%) experienced a mild to moderate adverse reaction to the contrast media, while only 2 of the 30 patients (7%) in the iopamidol group had similar side effects (p less than 0.005). Significant prolongations of the QT intervals occurred with the ioxaglate injections. The QT intervals increased from 402 +/- 46 to 442 +/- 59 ms (p less than 0.001) with the right coronary artery injection and similar changes were observed after the left coronary artery injection and left ventriculography. Significant ST-segment and T-wave amplitude changes also occurred in the ioxaglate group. With iopamidol injections, there were no significant changes in any of these parameters. After the left ventriculogram, there were similar decreases in the systolic arterial pressures in both groups (-14 +/- 10 mm Hg with ioxaglate and -21 +/- 9 mm Hg with iopamidol). The left ventricular end diastolic pressures increased after the ventriculogram in both groups (5 +/- 5 vs 2 +/- 3 mm Hg with ioxaglate and iopamidol, respectively, 60 seconds after the injection). This report demonstrates that mild to moderate adverse reactions, QT interval prolongations, ST and T-wave changes were significantly greater during coronary angiography with ioxaglate when compared with iopamidol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2916436 TI - Ultrastructural epithelial zonation of the primate endometrium (rhesus monkey). AB - The uterine endometrium of menstruating primates (rhesus monkey, human) consists of a germinal basalis that regenerates a transient functionalis during each menstrual cycle. The endometrium is further subdivided into 4 zones that differ histologically and in epithelial mitotic rate along the longitudinal axes of the uterine glands and microvasculature (Bartelmez et al: Contrib. Embryol. Carnegie Inst., 34:99-146, 1951; Bartelmez: Am. J. Obstet. Gynecol., 74:931-955, 1957; Padykula et al.: Biol. Reprod., 32:1103-1118, 1118, 1984; Biol. Reprod., in press, 1988). The zones are defined as follows: functionalis I, luminal epithelium; functionalis II (upper straight gland segments); basalis III (middle gland segments), and basalis IV (bottoms of the glands). The surrounding stroma and microvasculature also differ zonally. Ultrastructural epithelial differences are evident among the 4 zones during 3 distinct functional states during natural menstrual cycles and after ovariectomy: 1) basal level after ovariectomy and 2) estrogen dominance and 3) progesterone dominance. Zonal structural differences persist at a minimal level of differentiation after ovariectomy and thus zonation is an inherent property. During estrogen dominance, distinctive ultrastructural differences are evident among the 4 zones, such as epithelial cell heterogeneity in functionalis I and homogeneity in functionalis II. Also a distinctive glandular cell type occurs in basalis III and IV that is recognized by a highly irregular cisternal rough endoplasmic reticulum that permeates the cytoplasm. During progesterone dominance, ultrastructural differences exist among the 4 zones except for similarity between the epithelial cells of functionalis II and basalis III. Postovulatory epithelial cells of functionalis I and II and basalis III become postmitotic via progesterone inhibition but intracellular differentiation continues progressively. Postovulatory epithelial mitotic activity in basalis IV escapes progesterone inhibition as the [3H]thymidine labeling index continues to increase from 1 to 12% during the menstrual cycle (Padykula et al.: Reprod., 30(Suppl.1):92 (Abstr. 123), 1984). This post ovulatory proliferation coupled with progressive differentiation in basalis IV may represent a stem-progenitor set of cells for postmenstrual endometrial regeneration or alternatively for creation of the maternal placenta. PMID- 2916437 TI - Tracheobronchial epithelium in the adult rhesus monkey: a quantitative histochemical and ultrastructural study. AB - Previous studies of the intrapulmonary conducting airways of sheep and rabbit have demonstrated marked diversity in the epithelial populations lining them. Because studies of trachea and centriacinar regions of macaque monkeys suggested that primates may be even more diverse, the present study was designed to characterize the epithelial population throughout the airway tree of one primate species, the rhesus monkey. Trachea and intrapulmonary airways of the right cranial and middle lobes of glutaraldehyde/paraformaldehyde-infused lungs of five adult rhesus monkeys were microdissected following the axial pathway. Each branch was assigned a binary number indicating its specific location within the tree. The trachea and six generations of intrapulmonary airway from the right cranial lobe were evaluated for ultrastructure and quantitative histology as were those of the right middle lobe for quantitative carbohydrate histochemistry. Four cell types were identified throughout the tree: ciliated, mucous goblet, small mucous granule, and basal. The tallest epithelium lined the trachea; the shortest, the respiratory bronchiole. The most cells per unit length of basement membrane were in proximal intrapulmonary bronchi; the least, in the respiratory bronchiole. The nonciliated bronchiolar epithelial or Clara cell was restricted to respiratory bronchioles. Sulfomucins were present in the vast majority of surface goblet cells in the trachea and proximal bronchi. In proximal bronchi, neutral glycoconjugates predominated in glands and acidic glycoconjugates in surface epithelium. In terminal and respiratory bronchioles the ratio of acidic glycoconjugate to neutral glycoconjugate equaled that in proximal bronchi, although glands were not present. Sulfomucins were minimal in terminal airways. We conclude that the characteristics of the epithelial lining of the mammalian tracheobronchial airway tree are very species-specific. The lining of the rhesus monkey does not have the diversity in cell types in different airway generations observed in sheep and rabbit. Also, the populations lining these airways in the rhesus are very different from either the sheep or rabbit in number, proportions of different cell types, glycoconjugate content, and distribution of specific cell types. PMID- 2916438 TI - Porcine colonic lymphoglandular complex: distribution, structure, and epithelium. AB - Lymphoepithelium and cells specialized for uptake and transport of foreign matter are characteristic of antigen sampling organs, including lymphoglandular complexes (LGCs). Distribution, histologic structure, and epithelial ultrastructure of colonic lymphoglandular complexes were determined in 5- to 13 week-old pigs. LGCs averaged 1,231 in number per colon, displayed a characteristic distribution pattern, and were most evenly distributed in colons of older pigs. LGCs consisted of well-defined submucosal masses composed of lymphatic nodules and internodular lymphoid tissue penetrated by radially branching extensions of mucosal glands. Epithelial diverticula of each LGC entered the submucosa as a group through a circular collar derived from the muscularis mucosae. LGC epithelium contained goblet cells, cuboidal and columnar enterocytes, enteroendocrine cells, individual and clustered intraepithelial leukocytes, and cells morphologically compatible with follicle-associated epithelial cells/M cells. We regard the colonic LGC as a distinct mucosal lymphoid organ and suggest a significant role for it in local and systemic immune responses. The porcine colonic LGC may serve as a model for the human LGC. PMID- 2916440 TI - Septal collateralization: demonstration of canine intramyocardial collaterals. AB - The anatomical distribution of intramyocardial collateral arteries that develop from the septal to the other major coronary arteries was studied in dogs following gradual Ameroid occlusion of the circumflex artery. The septal artery was cannulated and injected with Batson's plastic compound resulting in a cast of the coronary circulation. Collateral vessels radiated from the septal vascular bed to both the circumflex and anterior descending arteries. The collaterals developed from the entire base-to-apex extent of the septal artery and were found on both the right and left sides of the septum. Collateral growth appeared to be more concentrated at the apex of the heart. The anatomical details of septal collateral circulation illustrate the importance of intramyocardial collateralization in the dog, which was thought to exhibit primarily epicardial collaterals. PMID- 2916439 TI - Formation of secretion granules in the Golgi apparatus of plasma cells in the rat. AB - The three-dimensional structure of the components of the Golgi apparatus was analyzed in plasma cells of rat duodenum. The spheroidal juxtanuclear Golgi apparatus was formed by a continuous ribbonlike structure composed of the following stacked elements. On the cis-face of the Golgi stack, there was a tubular membranous network referred to as the cis-element and/or a slightly dilated saccule perforated with small pores. The two or three subjacent saccules, which showed few pores, were slightly dilated and contained a fluffy granulofilamentous material. They were also perforated in register by cavities or wells containing 80-nm vesicles. The next one or two underlying elements were fenestrated saccules showing flattened portions as well as distended portions containing a homogeneous material denser than that seen in the overlying saccules. The last two or three elements of the stack showed a partially separated or "peeling off" configuration. These last elements consisted of prosecretory granules attached to flattened, empty-looking saccules showing buds at their surface; detached, more-or-less fenestrated, flattened saccules; and shrivelled residual trans-tubular networks. In the trans-region of the stack, in addition to numerous small vesicles, short membranous tubules, detached prosecretory granules, and denser fully formed secretion granules were also seen. These images were interpreted to indicate that secretory material present in the trans-saccules flows toward the dilated portions which become prosecretory granules. The trans-most elements seemingly peel off the stack to yield prosecretory granules and fragmenting trans-tubular networks. PMID- 2916441 TI - Lectin histochemistry of the embryonic heart: fucose-specific lectin binding sites in developing rats and chicks. AB - Glycoconjugates, particularly their sugar side chains, play important roles in embryonic development. Changes in cell-surface-associated glycoconjugates are known to affect cell differentiation, cellular interactions, and other developmental phenomena during embryogenesis. The embryonic heart goes through a series of complicated morphologic events during development. Of particular interest is morphogenesis of the outflow tract. This region of the embryonic heart originates from more than one cell population and undergoes a complex process of septation during formation of the great vessels. Histochemical analysis with a series of fucose-specific lectins conjugated to horseradish peroxidase has revealed the presence of a fucosylated glycoconjugate in the outflow tract of the developing heart. The results reveal further that the expression of the fucosylated glycoconjugate is stage-dependent and thus probably genetically regulated. The timing and distribution of staining with the lectin OFA suggest that this fucosylated glycoconjugate may play a role in directing the migration of neural crest cells into the heart and subsequent formation of the conus septum. PMID- 2916442 TI - Lectin histochemistry of the embryonic heart: expression of terminal and penultimate galactose residues in developing rats and chicks. AB - Rat embryos at days 10-18 of gestation and chicken embryos at days 3-6 of incubation were fixed and processed for lectin histochemistry. The distribution of binding sites for a lectin from the peanut Arachis hypogaea (PNA) conjugated to horseradish peroxidase (HRP) was determined on tissue sections both before and after enzymatic cleavage of sialic acid with neuraminidase (sialidase). Endocardial cushion tissue in the rat, but not in the chick, reacted with PNA-HRP prior to digestion with sialidase. Endocardium of both species (12 and 13 days in rat, 5 and 6 days in chick), particularly at the level of endocardial cushions, reacted strongly with the sialidase-PNA sequence; this staining decreased markedly after day 14 of gestation in the rat. PNA binding sites capped by sialic acid were most abundant in the developing rat heart during the critical period of endocardial cushion formation and decreased as development proceeded. The marked changes in the appearance and distribution of cardiac cell and tissue glycoconjugates during cardiogenesis support the concept that rapid changes occur in the structure of complex carbohydrates during embryonic and fetal development. The findings also suggest that such glycosylation-related events may be species specific. PMID- 2916443 TI - Energy expenditure in underweight free-living adults: impact of energy supplementation as determined by doubly labeled water and indirect calorimetry. AB - The effect of energy supplementation was evaluated in six underweight adults under free-living conditions. Customary energy intake (EI) over 4 wk and estimated body composition were defined. Then for 12 wk subjects were fed their customary EI under controlled conditions to assure stable energy reserve. Finally, intake was increased by a mean of 720 kcal/d for 8 wk adjusted to increase body fat from 9 to 18%. Body weight (means +/- SD) increased from 55.2 +/- 3.4 to 57.0 +/- 4.2 kg. Body fat gain was highly variable ranging from 0.6 to 3.8 kg. Energy expenditure (EE) by the factorial and doubly labeled water methods did not change. Fat storage accounted for 66% of the supplemental energy; 237 kcal/d remained unaccounted for. EE by the factorial method, which uses indirect calorimetry or isotopic measurements, were highly correlated (r = 0.8; p less than 0.01). Under the conditions of this study EI does not affect EE. The labeled water method permits the evaluation of energy expenditure in free-living conditions. PMID- 2916444 TI - Plasma cholecystokinin and pancreatic polypeptide responses after ingestion of a liquid test meal rich in medium-chain fatty acids in patients with chronic pancreatitis. AB - Plasma cholecystokinin (CCK) and human pancreatic polypeptide (hPP) responses after ingestion of a liquid test meal rich in medium-chain fatty acids (MCFA) were studied in patients with chronic pancreatitis with or without diabetes mellitus (DM). Integrated response of plasma CCK was significantly lower in patients with chronic pancreatitis and DM than in the two other groups. There was no statistically significant difference between the healthy control subjects and the patients with chronic pancreatitis without DM in the integrated responses of hPP and plasma CCK. These results indicate that diabetic patients with a greatly destroyed pancreas do not release as much CCK as do nondiabetic patients with a mildly impaired pancreas. An MCFA meal is therefore considered safe in patients with a mildly impaired pancreas. For diabetic patients, however, care should be taken not to exacerbate the DM. PMID- 2916445 TI - Menstrual cycle and voluntary food intake. AB - The relationship of food intake and the human menstrual cycle has not been well quantified. In this study, voluntary energy and sucrose intake of seven women, aged 24-43 y, were evaluated by the weighed-intake method over one entire menstrual cycle. Portable tape recorders facilitated the recording of food intake. Although daily fluctuations of energy intake were large, analysis of variance showed intake during the luteal phase to be significantly greater than during the periovulatory and follicular phases (p less than 0.05). From 95% simultaneous (Bonferoni) confidence intervals, the estimate of difference was 283 kcal greater during the luteal phase than the periovulatory phase; the estimate of difference was 214 kcal greater during the luteal phase than during the follicular phase. No significant differences in energy intake were found among the menstrual, follicular, and periovulatory phases. No significant relationship was found between sucrose intake and the menstrual cycle. PMID- 2916446 TI - Postpartum changes in maternal weight and body fat depots in lactating vs nonlactating women. AB - Maternal weight and body fat changes were studied in 56 women from delivery to 6 mo postpartum. Six-month weight losses (p less than 0.01) in exclusively breast feeding (BF), exclusively formula-feeding (FF), and combination breast- and formula-feeding mothers (CF) were 8.30 +/- 0.74, 8.19 +/- 0.96, and 7.22 +/- 0.74 kg respectively; however, only BF experienced a significant change between 3 and 6 mo. Suprailiac and subscapular skinfold thickness decreased over 6 mo (p less than 0.01) with the suprailiac region reflecting a significant feeding-method effect. Increases in triceps fatfold measurements at 3 mo suggest that a temporary redistribution of body fat occurs as the energy stores of pregnancy are mobilized. Lactating mothers consumed more (p less than 0.01) kilocalories (BF, 2055 +/- 435; CF, 2005 +/- 515) than did nonlactating mothers (FF, 1453 +/- 503). Age, parity, and prepregnancy weight exerted significant covariable effects. Results suggest that lactation does play a role in postpartum weight and body fat loss but that the current RDA may be too high to permit such losses. PMID- 2916447 TI - Lecithin intake and serum cholesterol. AB - To find out whether the consumption of lecithin has a more beneficial effect on serum cholesterol than does the consumption of equivalent amounts of polyunsaturated oils, we scrutinized 24 studies on the effect of supplementary lecithin intakes ranging from 1 to 54 mg/d. Most of the studies lacked an appropriate control group, had a small sample size, or had changes in intake of other foods because of increased energy intake from lecithin. In only four trials were attempts made to balance fatty acid intakes of control and experimental groups. There is no evidence for a specific effect of lecithin on serum cholesterol independent of its linoleic acid content or secondary changes in food intake. The observed lecithin-induced hypocholesterolemic effects found in various studies were artifacts caused by the design and the manner of data analysis, were mediated by other dietary changes, or were due to the linoleic acid present in lecithin. PMID- 2916448 TI - Fatty acid composition of serum cholesteryl esters and erythrocyte membranes as indicators of linoleic acid intake in man. AB - We compared the suitability of the linoleic-oleic acid ratio (L:O) of serum cholesteryl esters and erythrocyte membranes as indicators of dietary fatty acid composition. Forty-seven volunteers received a mixed natural diet with a polyunsaturated-saturated fatty acids ratio (P:S) of 0.2 for 3 wk and with P:S 2.0 for another 3 wk (HA group, 24 subjects) or vice versa (HY group, 23 subjects). Duplicate portion analysis revealed that dietary fat type was the only variable. The change in L:O in cholesteryl esters relative to the low P:S diet was 91.3 +/- 25.9% (means +/- SD) in the HA group and 85.1 +/- 18.8% in the HY group. The changes in erythrocyte membranes were 33.0 +/- 7.9% in the HA group and 22.8 +/- 4.9% in the HY group. Thus the effect on erythrocyte fatty acids was smaller but also less variable and the precision of the two measures was similar. Therefore the L:O of either blood component can be used as a marker of a subject's adherence to experimental diets differing in type of fat. PMID- 2916449 TI - Chylomicron triglyceride clearance: comparison of three assessment methods. AB - Three indirect methods for assessing chylomicron-triglyceride clearance were compared in 12 normolipidemic men. Oral and intravenous fat tolerance tests and a duodenal fat perfusion were performed in each subject by standard methods. Mean values for postprandial lipemia (2.27 +/- 1.8 mmol), Intralipid half-life (13.7 +/- 5.2 min), and chylomicron-triglyceride half-life (4.5 +/- 2.6 min) were similar to corresponding values reported previously for normolipidemic men. The sample correlation coefficient (r) was 0.84 between oral and intravenous fat tolerance tests, 0.84 between the oral fat-tolerance test and the duodenal perfusion method, and 0.82 between the intravenous fat-tolerance and the duodenal perfusion methods. All three methods showed a strong correlation between chylomicron-triglyceride clearance and fasting triglyceride concentrations. These findings indicate that the oral and intravenous fat-tolerance tests and the duodenal-perfusion method yield qualitatively similar assessments of chylomicron triglyceride clearance in normolipidemic men. PMID- 2916450 TI - Fibronectin turnover in the premature neonate measured with [15N]glycine. AB - Fibronectin is a large-molecular-weight glycoprotein present on most cell surfaces and in plasma. Plasma fibronectin concentrations in neonates are lower than those in adults and a direct relationship exists between plasma concentration and gestational age. We determined the half-life and fractional synthetic rate (FSR) of plasma fibronectin in the premature infant. Infants and adults received a loading dose of [15N]glycine followed by a constant infusion [15N]glycine incorporation into plasma fibronectin and urine hippurate was determined by gas chromatography-mass spectrometry. The plasma fibronectin FSR in the preterm neonates was 15.5 +/- 9.9%/d(means +/- SD) and the half-life was 5.55 +/- 2.25 d. Birth weight correlated inversely with plasma fibronectin half-life. In the adults the plasma fibronectin FSR ranged from 20 to 87%/d and half-life ranged between 0.79 and 3.47 d. These data suggest that decreased plasma fibronectin levels in preterm infants are due to reduced FSRs rather than to greater turnover of a relatively small plasma pool. PMID- 2916451 TI - Body composition and energy intake: do overweight women overeat and underreport? AB - The relationship between energy consumption and body composition was evaluated in 63 women by use of energy-intake values that were precisely measured in a metabolic unit and corrected for deviations from energy balance. Energy requirement for the maintenance of body weight was not significantly correlated with adiposity expressed as percent body fat. However, energy requirement was positively associated with lean mass (p less than 0.0001) whereas fat mass added no predictive value to the same multivariate regression equation. Self-reported energy intake (before the experiments) was not correlated with lean mass and was underestimated by lean subjects at least as much as by obese subjects. Discrepant findings in the literature concerning relationships between obesity and energy intake may be explained by reporting error and by the relative lean mass of obese vs nonobese women but not by systematic underreporting unique to obese subjects. PMID- 2916452 TI - Hypocaloric feeding in obese women: metabolic effects of medium-chain triglyceride substitution. AB - Medium-chain (MCT) and long-chain (LCT) triglyceride diets were compared during and after 4 or 12 wk of hypocaloric feeding in obese women to determine the effects on weight loss, ketones, nitrogen balance, and insulin action. After a base-line euglycemic clamp, two groups ingested an 800-kcal/d liquid diet with 30% of calories as LCT (group 1) or 6% of calories as LCT and 24% as MCT (group 2). Rate and amount of weight loss, serum ketones, and N balance were not different between groups. However, the subjects in group 2 (MCT) demonstrated an increase in glucose requirement to maintain euglycemia during the clamp after weight loss (delta 0.18 +/- 0.13 mmol.m-2.min-1) whereas subjects in group 1 (LCT) had a diminished requirement (delta -0.12 +/- 0.10, p = 0.036). Thus, an 800-kcal diet containing 24% of calories as MCT is safe and enhances insulin action but fails to increase the rate or amount of weight loss. PMID- 2916453 TI - Resting metabolic rate in lean and obese children: relationship to child and parent weight and percent-overweight change. AB - Two studies were conducted to assess differences in metabolic rate as a function of child weight (study I); and the interaction of child and parent weight (study II). In both studies obese children had higher resting metabolic rates (RMRs) than lean children (p less than 0.05). Child weight accounted for 72 and 78% of the variance in RMR in studies 1 and 2, respectively. Including parental weight did not improve the prediction of RMR. After 6 mo of treatment, obese children decreased percent overweight, whereas lean children showed no change (p less than 0.01). RMR in both groups remained unchanged after 6 mo. These results indicate that the RMR is higher in obese than in lean children, that changes in percent overweight that result from increases in height and no change in weight do not decrease RMR over 6 mo, and parent weight does not improve the prediction of child RMR. PMID- 2916454 TI - Meal effects on calcium absorption. AB - The effect of coingestion of a meal on calcium absorption efficiency was investigated using Ca carbonate, milk, and a new Ca delivery system, CCM. Six experiments with 168 rats and two experiments with 46 normal young women showed that coingestion of a light meal of varied composition enhanced absorption efficiency from all three sources by 10-30% above levels achieved when the test load was ingested without other foods. The differences taken as a whole were highly statistically significant. PMID- 2916455 TI - Serum triglyceride responses. PMID- 2916456 TI - Diets and plasma cholesterol. PMID- 2916457 TI - Olive oil and liver cholesterol. PMID- 2916458 TI - Cytologic features of fine-needle aspirates of hyalinizing trabecular adenoma of the thyroid. AB - The cytologic features of five cases of hyalinizing trabecular adenoma of the thyroid are reviewed. All of these cases had been initially interpreted as either suspicious or positive for malignancy. On retrospective review, many of the cytologic features did mimic those of other lesions, particularly papillary carcinoma. The smears tended to hypercellularity, and nuclei were often slightly enlarged with pale chromatin, intranuclear holes, and longitudinal grooving of the nuclear membrane. On the other hand, some cytologic features were more suggestive of medullary carcinoma--poor cohesion of cells with elongated and spindle cell forms and hyaline acellular areas. Awareness of the histologic and cytologic features of hyalinizing trabecular adenoma may enable the cytopathologist to avoid a false positive diagnosis of papillary carcinoma or medullary carcinoma, although it is unrealistic to expect a definitive diagnosis of hyalinizing trabecular adenoma. PMID- 2916459 TI - Ability of whole blood aggregometer to detect platelet hyperaggregability. AB - In this study the reliability of platelet aggregation in whole blood (WB) was investigated in clinical conditions associated with thromboembolic complications. Spontaneous (SPA) and collagen-induced platelet aggregation were evaluated both in whole and diluted blood by the impedance method and in platelet-rich plasma (PRP) by the Born aggregometer in 18 healthy subjects, 15 patients with ischemic heart disease (IHD), and 15 patients with insulin-independent diabetes. SPA occurred more often in WB than in PRP, and in WB the occurrence of SPA was significantly more frequent in the patient groups (4 of 15 patients with IHD and 6 of 15 diabetic patients) than in the controls (1 of 18). WB aggregation induced by collagen was significantly higher in patients with IHD and in diabetic patients than in controls (P less than 0.01), whereas diluted WB and PRP aggregation were not statistically different from controls either in patients with IHD or in diabetic patients. WB aggregation values were found to be related, although not very closely, to megathrombocyte count (r = 0.31, P less than 0.05) whereas not at all to platelet count or hematocrit. No relationship was observed between WB aggregation and disease severity (angiographic lesions and number of ischemic attacks) in patients with IHD and between WB aggregation and HbAlc values in diabetic patients. PMID- 2916460 TI - Variation in human blood high-density lipoprotein response to oral vitamin E megadosage. AB - In a preliminary attempt to distinguish random intrinsic and methodologic variations of blood lipid levels from any that have possibly been induced by ingestion of vitamin E, blood samples were analyzed in duplicate for lipids several times before and during oral vitamin E administration. Three of eight subjects showed temporally closely coordinated and maintained increases of high density lipoprotein cholesterol and apolipoprotein-A, total apolipoprotein-A, and the ratio of high-density to low-density cholesterols. Changes of other lipids in these three subjects, and lipid changes in the other subjects, were much less dramatic, fell within the range of intrinsic random variation or statistical uncertainty, and showed no significant trends. The results suggest that elevation of high-density lipoproteins in response to ingestion of megadoses of vitamin E is very much an individual characteristic and not uniformly typical of the population at large. The findings complement published examples of individual variation of response to vitamin E as an explanation of disagreements between other reports. PMID- 2916461 TI - Development of the gout tophus. An hypothesis. AB - Sequential stages have been demonstrated in the development of individual focal deposits of crystalline urate and associated cell infiltrates within subcutaneous gout tophi. The findings suggest that acini of macrophages are formed and that active cellular transport of urate from the interstitial fluid into the central zones of these structures accounts for the focal nature of crystallization within the tophus. This process seems to account for the formation of focal urate deposits up to some 1.5-2 mm in diameter. The corona then commonly disappears and adjacent deposits may fuse. These events may lessen the consequences of hyperuricemia. PMID- 2916462 TI - Platelet subpopulations in adult and geriatric males. AB - In this study, the authors wanted to investigate the volume, density, and percentage of three platelet subpopulations present in adult and geriatric males. Ninety subjects, between the ages of 20 and 40, were chosen for the adult group and 50 subjects, all older than age 70, were used for the geriatric group. The platelet subpopulations were separated with discontinuous gradients of Percoll. The results obtained from the three platelet subpopulations--low, intermediate, and high density--show different volumes and percentages in both the groups studied. From the information that larger platelets can be expected to have a longer life span, it was possible to hypothesize that platelets found in geriatric males have a reduced average life span. It is also clear that platelets exist that have similar volumes but different densities. PMID- 2916463 TI - Evaluation of IVAC Variable Pressure Volumetric Pump Model 560 for the delivery of red blood cells, adenine-saline added. AB - Mechanical pump systems for the delivery of intravenous solutions have been used for the transfusion of red blood cells. In this study, the IVAC Variable Pressure Volumetric Pump Model 560 was evaluated for that purpose using flow rates of 70 mL/hour and 999 mL/hour through 16-, 19-, and 23-gauge needles and an 18-gauge angiocatheter. The largest degree of hemolysis induced by the delivery system resulted in a mean increase of plasma hemoglobin of 150 mg/L (15 mg/dL); this is equivalent to the loss of 0.03% of the red blood cells. When programmed to deliver 15 mL of red blood cells, the IVAC 560 delivered 15.0 +/- 0.3 mL at a rate of 70 mL/hour and 14.9 +/- 0.3 mL at 999 mL/hour. The authors conclude that the IVAC 560 can be used to deliver red blood cells with a minimal, acceptable level of hemolysis. It also delivers an accurate and precise volume of red blood cells that may be an aid to the transfusionist. PMID- 2916464 TI - Cytodiagnostic urinalysis. Three years experience with a new laboratory test. AB - Cytodiagnostic urinalysis is performed by examining Papanicolaou-stained cytocentrifuge preparations of urine sediment. Nonrenal transplant patient results (N = 1,602) were reviewed. Renal hematuria was found in 37.7% of specimens, white blood cell casts in 11%, and renal tubule cell injury in 53%. The technique demonstrates significantly improved sensitivity to detect urine sediment abnormalities indicative of renal parenchymal disease. The technical requirements are readily available and easy to implement in the laboratory. Skills required for identification and quantitation can be acquired in a few weeks. PMID- 2916465 TI - The pathology of metastatic cardiac myxoma. AB - The authors describe a case of a "benign" cardiac myxoma with metastases to a previously unreported site, the right temporal bone. The cardiac tumor became evident five years after the bone tumor presentation. Patients with myxomas in unusual locations should have a complete cardiac evaluation. PMID- 2916466 TI - Mycobacterium kansasii diffuse pulmonary infection in a patient with acquired immune deficiency syndrome. Successful therapy with an antituberculous regimen. AB - Mycobacterium kansasii is a rare cause of disseminated mycobacterial infection in patients with the acquired immune deficiency syndrome (AIDS). It occurs as the index AIDS diagnosis in only 0.2% of AIDS cases. Previously reported cases of AIDS-associated M. kansasii infection have manifested as diffuse interstitial pneumonitis and diffuse small bowel inflammation and have been refractory to antimycobacterial therapy. The authors now report success in treating a hypoxemic patient with AIDS-associated M. kansasii diffuse granulomatous interstitial pneumonitis that was diagnosed by open lung biopsy. The patient has no evidence of mycobacterial disease after 12 months of therapy with isoniazid, rifampin, and ethambutol. PMID- 2916468 TI - Periodontal changes after experimentally induced intrusion of the upper incisors in Macaca fuscata monkeys. AB - We are studying the biologic aspects of vertical movement of teeth, which are often used in orthodontic treatment involving variations in alveolar tissue. In the present study, the four upper incisors of five infant Macaca fuscata monkeys were intruded vertically from 1.1 to 5.5 mm. The following effects were examined: (1) movement of the gingiva, (2) change in the depth of the gingival sulcus, and (3) microscopic effects on the alveolar tissue. The results were as follows. (1) The gingiva moved in the same direction that the teeth were intruded, but only about 60% as far. (2) The clinical crown shortened and the gingival sulcus deepened. The shortening of the crown and the deepening of the sulcus were both approximately 40% as much as the tooth intrusion. (3) There was no inflammation or swelling microscopically in the gingiva of either the experimental animals or the controls. (4) The epithelium was always attached in the cementoenamel junction, even when the tooth was intruded. As the tooth intrusion was increased, the dentoperiosteal fiber (DPF) and the dentogingival fiber (DGF) terminating in the cementum gradually parted from it; when the tooth was intruded more than 5.0 mm, few fibers terminated in the cementum. It was concluded that the gingival sulcus deepened with horizontal tooth intrusion because of an accumulation of gingival tissue applied with good oral hygiene--not because of swelling around the gingival margin or apical movement of the gingival pocket--and the DPF and the DGF were parted from the cementum gradually as the tooth intrusion increased. PMID- 2916467 TI - Condylar cartilage in the muscular dystrophic mouse. AB - The adaptability of condylar cartilage has been demonstrated previously after experimentally created functional alteration. This study was undertaken to examine the morphology of condylar cartilage in animals affected with a progressive muscular disease. Muscular dystrophic male mice (genotype: dy/dy, dy/+ x dy/+, Jackson Laboratory, Maine) and corresponding unaffected control mice were decapitated at ages 3, 6, 9, and 12 weeks, and their heads processed for histology. The cellular morphology of the condylar cartilage in the youngest age group was similar in dystrophic and control mice: the cartilage was a hypertrophic type. At ages 6 and 9 weeks, the maturational progression toward the nonhypertrophic form was observed in the dystrophic and control groups, the latter having flatter condylar heads. Differences were still evident at age 12 weeks. These observations were supported by measurements of the ratios of the mean cartilage thickness to condylar width (c/w), mean condylar height to width (h/w), and mean cartilage thickness to condylar height (c/h). This study supports the hypothesis that the adaptive nature of condylar cartilage may be regulated by the force levels to which the condyle is subjected. PMID- 2916469 TI - Cephalometric changes in Class II, Division 1 cases after orthopedic treatment with the bioactivator. AB - The bioactivator is an orthopedic appliance that has been used for 20 years in the treatment of Class II, Division 1 cases. The evaluation of its therapeutic effects was performed in this study of 76 9- to 10-year-old patients (at the beginning of treatment). The treated subjects were separated into two groups: group A (bioactivator only) and group B (bioactivator plus headgear). Group C comprised 14 untreated subjects selected as controls. Various statistical assessments were made to separate growth phenomena from treatment effects. It appears that the bioactivator has an effect not only on the dentition but also on the skeletal structures. In both treated groups, the maxillary changes were related to an increased anterior vertical growth and a posterior sagittal growth. The addition of extraoral force helped to achieve a posterior rotation of the upper jaw. When only the bioactivator was worn, the mandibular changes were more vertical than sagittal. The lower jaw appeared more forward, however. When the bioactivator and the headgear force were used simultaneously, the therapeutic effects seemed to be more sagittal than vertical, as if the occipitally directed force vector inhibits or at least exerts a control on the downward growth tendency. Without being significantly different statistically from one to the other, the treated groups showed a marked improvement of the sagittal jaw discrepancy. PMID- 2916470 TI - Treatment effects of the Herbst appliance. AB - The purpose of this study was to examine the results of treatment with a modified Herbst appliance. The pretreatment and posttreatment cephalometric and dental cast records of 32 consecutively treated Class II, Division 1 cases were evaluated. Results showed that the skeletal Class II correction was achieved by an average 1.5 mm of greater than normal forward mandibular growth in conjunction with a minimal "headgear" effect inhibiting maxillary growth. Dental Class II correction was achieved by significant amounts of distal bodily movement and tipping of the maxillary first molars combined with bodily forward movement of the mandibular first molars. Significant increases were seen in maxillary arch length and maxillary intercanine and intermolar widths, while the mandibular arch demonstrated few changes. Slight forward movement of the mandibular incisors was noted with no significant change occurring in the maxillary incisors. PMID- 2916471 TI - The craniofacial morphology in persons with maxillonasal dysplasia (Binder syndrome). A longitudinal cephalometric study of orthodontically treated children. AB - The aim of this investigation was to study the influence of orthodontic treatment on facial growth in subjects with maxillonasal dysplasia. The subjects were followed longitudinally from early childhood until growth was completed or almost completed. Fifteen patients, 9 boys and 6 girls, were orthodontically treated by conventional methods. They were compared with (1) another longitudinal group consisting of 13 orthodontically untreated children, 7 boys and 6 girls with the same syndrome, and (2) with a control material taken from computer-filed data on Swedish children and young adults with orthognatic profiles and normal occlusion. The orthodontic treatment led to acceptable dental conditions in 10 of the patients. No influence on craniofacial growth could be demonstrated. However, the mean facial polygons of the children showed that certain differences already existed at early ages between the treated subjects with a generally more severe form of the syndrome and the untreated children. The growth pattern seemed, however, to follow about the same rate in both groups. In six patients the orthodontic treatment was followed by surgical correction at adult age to solve their craniofacial problems. The optimum care of these patients requires an interdisciplinary treatment approach with thorough treatment planning by orthodontists in collaboration with oral and plastic surgeons. PMID- 2916472 TI - An American Board of Orthodontics case report. AB - A case report is presented of a Class II, Division 1 malocclusion with severe excess overjet, vertical maxillary excess, maxillary skeletal protrusion, and relative mandibular retrognathia. The case was treated according to the standards of the American Board of Orthodontics. PMID- 2916473 TI - Enamel wear caused by ceramic brackets. PMID- 2916474 TI - A clinical study of maxillary canine retraction with a retraction spring and with sliding mechanics. AB - The efficiency of maxillary canine retraction by means of sliding mechanics along an 0.018-inch labial arch and an AlastiK chain was compared with that using the canine retraction spring designed by Gjessing. The rate of canine retraction and degree of tipping, and rotation of the canines were studied in 21 subjects by one of these two methods on either side of the dental arch. Measurements were made in the mouth and on photographs of dental casts. The canine was retracted faster and with less distal tipping with the spring than with the sliding mechanics. The canine retraction spring was not superior to the sliding mechanics in controlling canine rotation during the retraction. PMID- 2916475 TI - What causes sexual assault? PMID- 2916476 TI - TEARS: does domestic violence play a role? PMID- 2916477 TI - Phenobarbital and respiratory complications in neonates receiving mechanical ventilatory support. PMID- 2916478 TI - A patient with IgA nephropathy. PMID- 2916479 TI - Kawasaki disease with thrombocytosis followed by thrombocytopenia purpura in the same patient. PMID- 2916480 TI - Fructose-1,6-diphosphatase deficiency: a 20-year follow-up. PMID- 2916481 TI - DICE: nonclinical causes of overtreatment. PMID- 2916483 TI - Pyloric stenosis in sick premature infants. PMID- 2916482 TI - Hidden salicylates. PMID- 2916484 TI - Fetal tissue transplantation. PMID- 2916485 TI - Protein intake and renal function in children. AB - To evaluate the effects of protein intake on renal tubular functions, seven metabolic studies were performed on five adolescents with mild, chronic renal insufficiency. After equilibration, patients were randomly assigned to two periods of four days each on either a high-protein diet (HPD) or a low-protein diet (LPD), with energy intakes remaining the same during both periods. High protein intake resulted in significantly higher mean (+/- SD) daily creatinine excretion and clearance rates. The HPD was associated with significantly increased excretion rates of potassium, phosphate, sulfate, and calcium. Net acid excretion with the HPD was nearly threefold higher than that observed with the LPD. These differences were unassociated with urinary pH, which remained similar with both diets. We conclude that different protein intakes affect urinary excretion of creatinine, potassium, phosphate, sulfate, calcium, and net acid. PMID- 2916486 TI - Increased nucleated red blood cell counts in small for gestational age infants with very low birth weight. AB - We evaluated the nucleated red blood cell (NRBC) counts in all infants with very low birth weight admitted to our neonatal intensive care unit from 1983 to 1986. There were 374 infants with birth weights of 500 g to 1500 g admitted in the first 24 hours after birth, but 31 died before studies were obtained. Of the remainder, 282 were appropriate for gestational age (AGA) and 61 were small for gestational age (SGA). Over 80% of both AGA and SGA infants were inborn and were evaluated within three hours of delivery. Nucleated red blood cell counts were significantly increased in SGA infants compared with AGA infants. The percent of infants with NRBC counts higher than 4.0 and 10.0 x 10(9)/L were 48% and 26%, respectively, in SGA infants compared with 19% and 6%, respectively, in AGA infants. Similarly, the percent of SGA infants with more than 40 or 100 NRBCs per 100 white blood cells were 62% and 36%, respectively, compared with 25% and 6%, respectively, in AGA infants. Data for specific weeks of gestation are provided and the differences were present at each gestational age. Recent data in fetuses with growth retardation, when blood was obtained directly from the fetal umbilical vein, showed an association between elevated NRBC counts and chronic hypoxemia. When increased NRBC counts are seen soon after birth, the possibility of a chronic intrauterine insult should be considered. PMID- 2916487 TI - Stress experienced during pediatric residency training. Its causes, consequences, recognition, and solutions. PMID- 2916488 TI - Patient care, resident stress, and government regulation. PMID- 2916489 TI - Puberty in the syndrome of septo-optic dysplasia. AB - To determine the patterns of puberty associated with the syndrome of septo-optic dysplasia, 13 older children with optic nerve hypoplasia and hypopituitarism were studied. Three patterns of puberty were observed: early, rapidly progressive puberty (group 1); appropriately timed puberty (group 2); and delayed puberty associated with gonadotropin deficiency (group 3). In the six patients in group 1, puberty began at an early bone age. Pubertal changes progressed rapidly and the bone age advanced faster than chronologic time so that, despite a normal to increased growth rate, growth potential was lost. Group 2 comprised three patients with multiple pituitary hormone deficiencies but without gonadotropin deficiency who had the timing and progression of puberty expected in hypopituitarism. The four patients in group 3, all with multiple pituitary hormone deficiencies, had gonadotropin deficiency requiring sex steroid replacement. PMID- 2916490 TI - Clinical indicators of intracranial lesion on computed tomographic scan in children with parietal skull fracture. AB - We conducted a review of 98 cases of pediatric traumatic parietal skull fracture in which computed tomographic (CT) scans of the head were obtained during a seven year period. There were 69 instances of an associated intracranial lesion identified in 47 children, including parenchymal injury (23), epidural hematoma (17), subdural hematoma (11), cerebral edema (ten), and subarachnoid hemorrhage (eight). Compared with 51 other children with parietal skull fracture and normal CT scans, the clinical characteristics significantly associated with the presence of an intracranial lesion were symptoms of neurologic dysfunction (loss or altered level of consciousness and/or seizure activity), neurologic compromise on examination (altered level of consciousness and/or focal deficit), or complicated skull fracture (bilateral, diastatic, and/or depressed). Of the 47 children with an intracranial lesion on CT scan, 44 had at least one of these significant clinical characteristics (sensitivity, 93%; specificity, 50%; positive-predictive value, 62%; and negative-predictive value, 96%). Children who sustain traumatic parietal skull fracture commonly experience associated intracranial injury. Those with evidence of neurologic deficit or complicated skull fracture are at particularly high risk, and should receive cranial CT scan evaluation. PMID- 2916491 TI - Iron deficiency in athletes. Insights from high school swimmers. AB - Previous studies have indicated a high incidence of nonanemic iron deficiency in high school runners, but little is known regarding participants in other sports. The hematologic and iron status of 30 high school swimmers was assessed at the beginning and end of a competitive swim season. Iron depletion (serum ferritin level less than 12 micrograms/L) was initially present in 46.7% of the girls and none of the boys, yet among those subjects with hypoferritinemia there was no evidence of impaired red blood cell production. Serum haptoglobin levels were normal and did not correlate with serum ferritin levels. No significant change was observed in ferritin, hemoglobin, or haptoglobin concentrations during the course of the season. Dietary intake of iron was poor, particularly in the girls, in whom it averaged 43% of the recommended dietary allowance. Menstrual histories suggested an inverse relationship between the amount of menstrual flow and the serum ferritin level. These findings indicate a high prevalence of nonanemic iron deficiency in female high school swimmers that bears no relationship to swim training. Dietary inadequacies and menstrual blood flow appear to be important contributors to the hypoferritinemia observed in these athletes. PMID- 2916492 TI - Treatment of the young child with postoperative central diabetes insipidus. AB - A continuous intravenous infusion of aqueous vasopressin (dosage range, 1.0 to 3.0 mU/kg/h) was administered to two patients (respective ages, 2 weeks and 3 years 1 month) who had postoperative central diabetes insipidus to determine if this mode of therapy is helpful in the very young patient. In both patients the polyuria and serum hyperosmolality were corrected. These findings suggest that an intravenous infusion of aqueous vasopressin can provide satisfactory control of the polyuria and electrolyte disturbances found in young children with acute postoperative central diabetes insipidus. PMID- 2916493 TI - Infections and sickle cell disease in Eastern Saudi Arabian children. AB - The rate and pattern of infections in 144 Saudi Arabian children with sickle cell disease (SCD) and matched normal control subjects are reported. All diagnoses of SCD were made at birth by means of screening blood from the umbilical cord. The children were prospectively followed up from birth to 4 years of age. Severe bacterial infections occurred in none of the children with SCD; one of the control children developed pneumococcal meningitis. Acute gastroenteritis was significantly more common among patients with SCD. For the first year of life, patients with SCD had significantly more infections than did the control children; but the reverse was true in the group that was 37 to 48 months of age. Considering all types of infections for all age groups, no difference was noted between patients with SCD and control subjects in terms of infection rate or related hospital admission. There were no deaths caused by infection in this series. We conclude that Saudi Arabian infants and young children of oasis origin with SCD are not at increased risk of infections compared with healthy children of the same age. PMID- 2916494 TI - Exercise-induced differences in cardiac output, blood pressure, and systemic vascular resistance in a healthy biracial population of 10-year-old boys. AB - Previous studies have documented systolic blood pressure differences in response to dynamic exercise when blacks were compared with whites. This study was performed to validate these data and to determine if the cardiac output and systemic vascular resistance responses to exercise are different in a biracial population of 10-year-old boys. Nineteen blacks and 31 whites underwent maximum supine graded exercise tests with Doppler determination of cardiac output and measurement of systolic and diastolic blood pressure and systemic vascular resistance. The blacks had a body surface area that was marginally larger than that of the whites, but no differences were noted in height or weight. Working capacities, when indexed by weight, were virtually identical between the two groups. No differences were noted in either systolic or diastolic blood pressure during preexercise, maximum exercise, or early and late recovery. White males had significantly higher cardiac indexes during preexercise, maximum exercise, and early and late recovery. Black males had greater systemic vascular resistance during preexercise, maximum exercise, and early and late recovery. Thus, the black children's blood pressure responses to exercise were comparable with those of the white children but they had a greater systemic vascular resistance and lower cardiac index. These racial differences may serve as potential markers for the prehypertensive state. PMID- 2916495 TI - Residency training in general pediatrics. Career direction of primary care graduates. PMID- 2916496 TI - Mortality with increasing assisted ventilation of very-low-birth-weight infants. AB - From Jan 1, 1977, to Jan 1, 1987, very-low-birth-weight (VLBW) infants consumed almost 90% of total patient-days of assisted ventilation of all infants born in one tertiary perinatal center. In the latter five years compared with the first five years, increasing resources allowed proportionately more VLBW infants to be offered assisted ventilation, and the patient-days of assisted ventilation consumed per live birth rose by almost 60%. All VLBW infants did not benefit equally from the increased assisted ventilation. Mortality in infants with birth weights below 1200 g decreased; unexpectedly, mortality in larger VLBW infants (birth weights, 1200 g to 1499 g) rose (relative odds, 3.11; 95% confidence intervals, 1.21 to 7.99). Despite the increased consumption of ventilator resources, there was no substantial impact on overall mortality in VLBW infants. PMID- 2916497 TI - Comparison of airway pathologic lesions after high-frequency jet or conventional ventilation. AB - High-frequency jet ventilation in neonates has been associated with airway damage ranging from focal necrosis to complete airway obstruction with mucus and severe necrotizing tracheobronchitis. However, studies have lacked consistent criteria for assessment, and jet ventilation systems have varied widely. We compared autopsy and histopathologic findings in six neonates who died after prolonged jet ventilatory support with findings in six matched controls who died after receiving conventional ventilatory support. Jet ventilation consisted of a pressure-limited, time-cycled, flow-interrupter-type system. The airways of all patients were assessed by the histopathologic scoring system of Ophoven et al. No differences were observed between neonates who received jet ventilation or conventional ventilation. We believe that the risk of airway damage should not preclude the use of jet ventilation, although further monitoring is imperative. PMID- 2916498 TI - Radiological case of the month. Right-upper-lobe esophageal bronchus (with VATER anomalies). PMID- 2916499 TI - Radiological case of the month. Bubble gum bezoar. PMID- 2916500 TI - Picture of the month. Skin diseases. PMID- 2916501 TI - The epidemic hysteria dilemma. PMID- 2916502 TI - Cutis verticis gyrata and chromosomal abnormalities. PMID- 2916503 TI - A benign cause of intermittent bradycardia of prematurity. PMID- 2916505 TI - Injury prevention: drowning. PMID- 2916504 TI - Beriberi in a Southeast Asian adolescent. PMID- 2916506 TI - Bone mineral status in hypopituitarism. PMID- 2916507 TI - Occult bacteremia in children with simple febrile seizures. PMID- 2916508 TI - Dexamethasone for children with bacterial meningitis. Should it be routine therapy? PMID- 2916509 TI - Respiratory syncytial virus outbreak on American Samoa. Evaluation of risk factors. AB - Acute respiratory illness is one of the leading causes of childhood mortality in developing nations. We investigated an increase in hospitalizations of children less than 2 years old for severe lower respiratory tract illness (LRI) from October 1986 through December 1986 on the island of American Samoa. Hospitalization rates were highest in children less than 6 months of age (60 of 1000 compared with 22 of 1000 for those 6 to 11 months of age, and seven of 1000 for those 12 to 24 months of age). The outbreak was more severe than in previous years, with ten (19%) of 54 patients admitted to the intensive care unit (ICU) compared with three (7%) of 42 and one (3%) of 40 during the same months of 1985 and 1984. Two patients died. Most patients had clinical bronchiolitis; of 34 patients tested, serologic or nasal aspirate evidence of recent respiratory syncytial virus (RSV) infection was found in 18 (53%). A study of patients younger than 1 year of age demonstrated that patients hospitalized with LRI were more likely to have a household member who smoked cigarettes (18/20, 90%) than outpatient controls without recent respiratory illness (8/15, 53%). Maternal sera obtained between December 1985 and October 1986 showed no protective effect of either detectable IgG or neutralizing antibody to two major groups of RSV. Our study documents the involvement of RSV in an outbreak of severe LRI among infants in a tropical area and further suggests that exposure to cigarette smoke is a risk factor for LRI infants. PMID- 2916510 TI - International adoption. An introduction for physicians. PMID- 2916511 TI - Recurrent injuries in schoolchildren. AB - Past work identifying "accident-prone" children with disproportionate rates of injury has been based on clinical data gathered in office, clinic, or emergency department settings. To avoid the biases inherent in such designs, we studied recurrent injuries in a school district population, utilizing a prospective surveillance system to identify injuries meeting standardized criteria. During three school years we observed 54,874 students, ranging in age from 6 to 18 years, for recurrent injuries, which were defined as those occurring in a year in which two or more injuries were reported for the child. Five hundred seventy three recurrently injured children (1% of the school district population) sustained 1405 injuries (17% of the overall injury experience), a proportion significantly but only slightly greater than that expected on the basis of chance alone (14%). Most recurrently injured children were injured in only a single year, with only 15 children sustaining injuries in all three study years. Age, sex, and type of school were significant correlates of recurrent injury rates, with junior high school students, boys, and students attending schools with alternative educational programs having the highest rates of injury recurrence. The findings indicate that (1) a small group of schoolchildren sustain a disproportionate share of the overall injury experience, (2) the majority of recurrently injured children experience only transient periods of enhanced injury risk, and (3) preventive strategies may benefit from investigation of developmental and social environmental factors that alter such risk. PMID- 2916512 TI - Home oxygen therapy for chronic lung disease in extremely low-birth-weight infants. AB - Chronic lung disease that requires prolonged oxygen therapy commonly complicates the recovery of extremely low-birth-weight infants (less than 1000 g). We report follow-up data through 18.5 +/- 0.9 (mean +/- SEM) months of age in 30 extremely low-birth-weight infants (birth weight, 783 +/- 24 g; gestational age, 26.0 +/- 0.3 weeks) who were discharged home receiving supplemental oxygen. Oxygen was prescribed to maintain arterial oxygen saturation at 95% or greater. At discharge, postconceptional age was 40.5 +/- 0.6 weeks, and weight was 2220 +/- 50 g. Duration of home oxygen therapy was 4.5 +/- 0.5 months. The mean weight percentile increased from less than 5 to 23 between discharge and the last follow up. All infants survived; only 6 required hospitalization for acute medical illnesses. We conclude that carefully supervised home oxygen therapy permits the safe early discharge of selected extremely low-birth-weight infants with chronic lung disease. PMID- 2916513 TI - Subhypothalamic high-intensity signals identified by magnetic resonance imaging in children with idiopathic anterior hypopituitarism. Evidence suggestive of an 'ectopic' posterior pituitary gland. AB - Magnetic resonance imaging in two children with idiopathic hypopituitarism demonstrated a signal of high intensity near the optic tract that was consistent with the signal produced by posterior pituitary tissue. Patient 1 was a 15-year old girl with panhypopituitarism but intact posterior pituitary function. Computed tomography disclosed widening of the superior aspect of the pituitary stalk and a partially empty sella. Magnetic resonance imaging disclosed a 3-mm high-intensity signal abutting the optic tract in the midline just above the sella. The pituitary stalk was not clearly defined, the pituitary gland was small, and the sella was filled with cerebrospinal fluid. Patient 2 was a 12-year old boy with isolated deficiency of growth hormone secretion. Findings from magnetic resonance imaging and computed tomography were similar to those in patient 1. These data suggest that the high-intensity magnetic resonance imaging findings represent a displaced or "ectopic" posterior pituitary gland, and that the hypopituitary state is due to an insult to the pituitary stalk. PMID- 2916514 TI - Effects of theophylline on behavior and learning in children with asthma. AB - This study examined the potential side effects of theophylline on behavior, attention, memory, and fine motor function in children with asthma. Seventeen children of normal intelligence who were intermittent theophylline users were recruited. Each was not taking medication at the initiation of the study. During the study, each child took the study medication (Theo-Dur tablets, 14 to 16 mg/kg per day or their usual dose, whichever was higher, or placebo) divided every 12 hours for 3 1/2 days (seven doses). A double-blind crossover design was employed such that each subject was randomly assigned to a group receiving theophylline/placebo or placebo/theophylline. After the first period, subjects were tested on a neuropsychological battery designed to assess cognitive performance, while the children, parents, and teachers filled out questionnaires concerning behavior and attention. The same procedure was repeated two weeks later (period 2) under the opposite drug condition. Data were analyzed by means of an analysis of variance, with time (period 1 vs period 2 [performance]) as a repeated measure and medication group as a between-subjects factor. Dependent variables consisted of 27 measures of performance, behavior, and attention. Only one of the 27 analyses revealed a significant group by time interaction. This analysis suggested a significant improvement in memory while taking theophylline; however, a different form of the same test showed no effect. Children and parents also completed a side-effects scale under both drug conditions. When the children were taking theophylline, parents and children noted that the children had more stomachaches and children noted more "shaking hands." The following observations suggest that the failure to find significant behavioral side effects while taking theophylline is not due to the relatively small sample size: (1) Almost all of the analyses fell far short of statistical significance, with findings indicating no trends toward poor performance while taking medication. (2) Correlations between the theophylline level and change in performance clustered around zero, with positive and negative values occurring with about equal frequency. (3) Neither parents nor children could accurately guess the child's medication condition. Thus, although there have been numerous reports on the behavioral side effects of theophylline, such reactions were not revealed in this study. PMID- 2916515 TI - Radiological case of the month. Hemangioma of the thigh. PMID- 2916516 TI - Gonorrheal vulvovaginitis, labial fusion and imperforate hymen. PMID- 2916517 TI - Hyperplastic colonic polyps as a marker for adenomatous colonic polyps. AB - Hyperplastic colonic polyps are generally regarded as being of little or no clinical consequence. Recently, however, hyperplastic polyps have been found to share numerous functional similarities with colorectal carcinoma. To determine whether the presence of an isolated left-sided colonic hyperplastic (metaplastic) polyp could serve as a marker for more proximal synchronous adenomatous colonic polyps, we retrospectively analyzed all consecutive colonoscopic polypectomies performed over an 18-month period at two medical centers. It is the policy at both institutions to remove or biopsy all polyps, regardless of size. Indications for colonoscopy included known or previous colonic polyps or carcinoma, hemoccult positive stool, lower gastrointestinal bleeding, iron deficiency anemia, abnormal barium enema, inflammatory bowel disease, abdominal pain, and family history of colon cancer. The location of adenomatous polyps and hyperplastic polyps was recorded and compared. One hundred sixty-three of 845 consecutive patients (19.3%) had at least one colonic polyp. The prevalence of adenomatous polyps alone was 10.3%, hyperplastic polyps 9%, and both types 1.9%. The prevalence rate for an adenomatous polyp in patients without a hyperplastic polyp was 15%. In contrast, among patients with a hyperplastic polyp, 49% had a synchronous adenomatous polyp. Only 3.4% of patients had an adenomatous polyp proximal to the splenic flexure when no polyps were present in the left colon. Conversely, among the 29 patients in whom an isolated hyperplastic polyp was found in the left colon, there was a 32.5% prevalence of adenomatous polyps in the proximal colon (p less than 0.01). The results of this study suggest that left-sided hyperplastic colonic polyps (generally within the reach of a screening sigmoidoscopy) serve as a marker for neoplastic polyps. PMID- 2916518 TI - Colonic motor response to eating: a manometric investigation in proximal and distal portions of the viscus in man. AB - The motor response of the human colon to a meal is still poorly characterized. Such data as are available were obtained chiefly for the distal colonic portions with myoelectrical techniques. For these reasons, we investigated proximal and distal colonic motor responses to food ingestion in a rather large group of healthy subjects. Twenty-nine healthy volunteers were studied with a colonoscopically positioned multilumen manometric probe and low-compliance infusion system. Recordings were obtained for 2 h during fasting and for 3 h after the subjects had eaten a 1000-kcal standard mixed meal. During fasting, motility was quite low, and no significant differences between proximal and distal portions were seen. After eating, each portion significantly increased its motor activity throughout the subsequent recording period, but there were differences in the time course in the response to eating for different colonic segments. Proximal portions (especially the transverse colon) had first a sudden maximal increase and then a decrease, whereas the distal ones had a slower and more sustained increase in activity. These findings are of interest, especially for comparison with those of patients with suspected motor dysfunction of the large bowel. PMID- 2916519 TI - Does gender or the menstrual cycle affect colonic transit? AB - Controversy exists as to whether slowing of colonic transit occurs in the high progesterone luteal phase of the menstrual cycle. To clarify this issue, colonic transit studies using radiopaque markers were performed on 10 women in the follicular phase, 10 women in the luteal phase of the menstrual cycle, and five women on oral contraceptives, and the results were compared with transit times in 11 male controls. No significant differences in colonic transit were found between either phase of the menstrual cycle. Colonic transit in women was slower than in men, but this was not statistically significant. In the clinical setting, therefore, colonic transit studies can be performed throughout the menstrual cycle or when taking oral contraceptives. In addition, a single standard for normal values can be used for both men and women. PMID- 2916520 TI - Patterns of colonic transit in chronic idiopathic constipation. AB - Rectosigmoid motility, anal manometry, and radiopaque marker studies have suggested the presence of several patterns of altered colonic transit in patients with chronic idiopathic constipation. Colonic transit scintigraphy was used to evaluate 23 constipated patients. After oral passage of a tube to the cecum, 50 microCi of 111In-diethylenetriaminepentaaceticacid (111In-DTPA) were instilled, and abdominal images were obtained for 48 h with a gamma camera. The 95% confidence limit for the geometric center in normals at 24 h was used as a criterion to differentiate patients with colonic inertia from those with functional rectosigmoid obstruction. In patients with functional rectosigmoid obstruction, colonic transit was essentially normal. In colonic inertia, transit was delayed in the cecum and ascending colon, hepatic flexure, and transverse colon. These two distinct patterns of colonic transit may have different pathogenetic and therapeutic implications. PMID- 2916521 TI - Usefulness of culture, histology, and urease testing in the detection of Campylobacter pylori. AB - Several tests have been described which detect the presence of Campylobacter pylori (CP) in the human upper gastrointestinal tract. Antral biopsies from 160 endoscopies were evaluated for the presence of CP; four tests readily available to the practicing endoscopist were used: two urease tests [CLOtest and microtiter biopsy urease test (MBUT)], hematoxylin and eosin staining, and culture. Sensitivity and specificity of each was evaluated and found to be near 90%, except for culture, which was less sensitive. The presence of peptic disease on endoscopy, and age greater than 50 yr, did play a small role in the sensitivity and specificity of the tests. With the advantage of lower cost, ease, and rapidity of performance, either the CLOtest or MBUT is recommended for the standard endoscopic evaluation for CP. PMID- 2916522 TI - Genesis and recovery of ethanol-induced gastric lesions in rats: possible involvement of prostaglandin D2. AB - We investigated the different effects of administration of high and low concentrations of ethanol (from 3% to 50%) on gastric mucosa in rats in relation to the changes in prostaglandin (PG) levels. Gastric lesions were induced by 50% ethanol, and all kinds of PGs were significantly decreased 1 h after administration, concomitantly. Thirty percent ethanol did not induce gastric lesions and had no effects on PG levels. Five percent ethanol significantly increased 6-keto-PGF1 alpha, PGF2 alpha, and PGE2 levels. Ten percent ethanol increased significantly PGD2 level. Premedication with sucralfate protected significantly gastric mucosa against 50% ethanol, and maintained PG levels, concomitantly. We also investigated the recovery time course of gastric lesions by 50% ethanol. Gastric lesions did not recover significantly after 24 h, recovered considerably after 48 h, and fully after 96 h. Levels of 6-keto-PGF1 alpha, PGF2 alpha, and PGE2 were fully recovered 24 h after exposure to 50% ethanol; however, a significant decrease in PGD2 level still was observed. PGD2 was recovered significantly after 48 h. These results indicate that different concentrations of ethanol induce different effects on gastric mucosal PGs, and that not only PGE2, but also other PGs, especially PGD2, might be linked with the genesis and recovery of gastric lesions by 50% ethanol. PMID- 2916523 TI - The diagnosis of esophageal candidiasis in patients with acquired immune deficiency syndrome: is endoscopy always necessary? AB - Oral and esophageal candidiasis represents a common infection in patients with acquired immune deficiency syndrome (AIDS). Because the relationship between the infection in both sites is not well known, we submitted to routine upper digestive endoscopy 57 patients with AIDS. Furthermore, we evaluated the diagnostic accuracy of oral candidiasis and esophageal symptoms as markers of Candida esophagitis. Oral and esophageal candidiasis were found in 52% and 48% of patients, respectively, whereas symptoms of esophageal origin were referred to by 60% of patients successively documented to have an esophageal infection. The sensitivity of esophageal symptoms and oral candidiasis alone, as indexes of an esophageal infection, was 60% and 88%, and their specificity was 100% and 81%, respectively. The combination of these two parameters improved their degree of diagnostic accuracy (sensitivity 93%, and specificity 100%), whereas the predictive value of their simultaneous presence or absence was 100% and 96%, respectively. These results document that routine endoscopy to verify the presence of esophageal candidiasis in all of the patients with AIDS is unnecessary; it could be reserved for selected subgroups such as those with esophageal symptoms despite systemic antifungal treatment, and for patients with AIDS-related complex presenting oral candidiasis without symptoms of esophageal origin. PMID- 2916524 TI - Concomitant primary hemochromatosis and beta-thalassemia trait: iron depletion by erythrocytapheresis and desferrioxamine. AB - Six men and one woman with mild anemia due to beta-thalassemia trait and major iron overload attributable to concomitant primary hemochromatosis were treated by erythrocytapheresis to remove iron, combined with subcutaneous desferrioxamine in the four cases with greater iron load. Depletion was achieved by iron removal of 4.5-15.1 g after 9-24 months' treatment. No side effects were observed, suggesting that such a regimen is effective and safe in this particular subgroup of hemochromatotics. PMID- 2916525 TI - Comparative acute effects of diflunisal and indomethacin on renal function in patients with cirrhosis and ascites. AB - Nonsteroidal anti-inflammatory drugs such as indomethacin induce a rapid reduction in renal perfusion and blunt the effects of diuretics in patients with cirrhosis and ascites. Nonacetylated salicylates reportedly cause less reduction in renal prostaglandins than do aspirin and other nonsteroidal anti-inflammatory drugs. To determine whether nonacetylated salicylates affect renal function, we compared diflunisal with indomethacin in nine patients with cirrhosis and ascites. One 50-mg dose of indomethacin reduced inulin clearance (91 +/- 11 to 76 +/- 11 ml/min) and blunted furosemide-stimulated natriuresis (58 +/- 12 to 36 +/- 9 mEq/h) and diuresis (1103 +/- 148 to 809 +/- 170 ml/h, all p less than 0.05). Three doses of diflunisal had no effect on inulin clearance (94 +/- 16 ml/min), natriuresis (60 +/- 12 ml/h), or diuresis (1041 +/- 112). Indomethacin caused greater reduction in urinary prostaglandin E2 (50% vs. 10%) and in serum thromboxane (94% vs. 80%) than diflunisal (p less than 0.05). Thus, nonacetylated salicylates avoid renal impairment and may be the preferred nonsteroidal anti inflammatory drug in patients with cirrhosis and ascites. PMID- 2916526 TI - Comparative efficacy of psychometric tests in detection of subclinical hepatic encephalopathy in nonalcoholic cirrhotics: search for a rational approach. AB - To compare the efficacy of various psychometric tests in the detection of subclinical hepatic encephalopathy (SHE), cerebral functions were studied in 20 nonalcoholic cirrhotics without overt encephalopathy and in 18 matched healthy controls. Wechsler Adult Intelligence Scale (WAIS) indicated that verbal ability was preserved in all cirrhotics. Of the WAIS performance tests, block design test (BDT) was abnormal in 11 (55%), picture arrangement in 10 (50%), object assembly in eight (40%) and digit symbol in six (30%) patients. Taken together, these tests diagnosed SHE in 14 (70%) patients. Number connection test (NCT) alone, on the other hand, was abnormal in 13 (65%) patients. A combination of NCT and BDT yielded the diagnosis of SHE in 15 (75%) patients. An important measure of the reliability of the diagnosis of SHE was that NCT and BDT were independently abnormal in 10 of these patients. Both NCT and BDT were found easy and quick to administer. In conclusion, our results argue in favor of using a combination of NCT and BDT for a rapid and accurate diagnosis of SHE in patients with cirrhosis of the liver. PMID- 2916527 TI - Significance of various classes of anti-HBc in individuals with chronic asymptomatic HBV infection. AB - Among 108 individuals with chronic asymptomatic hepatitis B virus infection, liver biopsies and serological investigation were performed simultaneously to determine the correlations of anti-HBc with the infection level of the liver pathology. The results showed that the prevalence of IgA and IgM anti-HBc, and the titers of IgA, IgM, and total anti-HBc, correlated with the liver damage. IgA anti-HBc was most prominent, being present in the whole group of patients with chronic active hepatitis with cirrhosis, and was absent in the whole group of asymptomatic carriers with normal histology. There were no linkages of IgA and IgM anti-HBc with the infectivity; in addition, the titer of total anti-HBc correlated inversely with the viral replication. PMID- 2916528 TI - Hiccups and esophageal dysfunction. AB - Presented herein are the detailed esophageal manometric, radiologic, ambulatory pH, and scintigraphic findings from a patient who developed protracted and recurrent hiccups (singultus) after a lateral medullary infarction. Because of the usually transient and benign nature of hiccups, previous reports on esophageal dysfunction during hiccups have been sporadic and confined to manometric findings. Utilizing various esophageal function techniques, the main features observed during hiccups were esophageal body dilation and aperistalsis, absent lower esophageal sphincter relaxation in response to swallowing, poor emptying of the distal two-thirds of the esophageal body, and low distal esophageal pH. Most of these features normalized in the absence of hiccups. A comparison is made of these findings during prolonged hiccups with those of esophageal achalasia. PMID- 2916529 TI - Perforated duodenal ulcer after gastric bypass surgery. AB - Gastric bypass procedures have been used widely in the surgical therapy of morbid obesity. Evidence exists that the bypassed gastric segment retains its ability to secrete acid. Acid-related ulceration and obstruction of the proximal gastric pouch after surgery have been well documented, but duodenal ulceration after gastric bypass has yet to be reported. We present the first reported case of duodenal ulceration and perforation after gastric bypass surgery for morbid obesity. This case demonstrates that acid-related gastroduodenal disease may occur in the bypassed gastrointestinal tract. Consideration should be given to this area in evaluating upper gastrointestinal bleeding and abdominal pain after gastric bypass. Because barium contrast studies may not adequately evaluate bypassed segments, and standard gastroscopes are not long enough to reach these areas, the use of longer endoscopes may be necessary to confirm the presence of gastroduodenal disease after gastric bypass. PMID- 2916530 TI - A case of double pylorus accompanied by adrenal adenoma. AB - We report here a case of double pylorus diagnosed endoscopically in a patient with adrenal adenoma. A 44-yr-old man was found to have double pylorus during examinations for recurrent epigastric pain and obesity. We think that the formation of double pylorus in this case resulted from recurrent peptic ulcer which, in turn, probably was induced by the hypersecretion of endogenous corticosteroids accompanying adrenal adenoma. PMID- 2916531 TI - Familial occurrence of anomalous pancreaticobiliary duct union associated with gallbladder neoplasms. AB - The authors present two cases of anomalous pancreaticobiliary duct union that occurred in a mother and her daughter; the former was associated with gallbladder adenocarcinoma, and the latter, gallbladder adenoma with high grade dysplasia. This disorder has been considered a developmental anomaly, although the true etiology has not been known. This is the first report of familial occurrence of this anomaly, and it may point to the presence of a genetic factor in its development. Another implication is the presence of histological features which suggest the possible sequence of anomalous pancreaticobiliary duct union to intestinal metaplasia to adenoma or dysplasia to cancer of the gallbladder. PMID- 2916532 TI - Protein-losing gastroenteropathy in association with immune deposits in gastrointestinal mucosal capillaries. AB - A 30-yr-old man presented with anasarca and visual disturbance. The serum albumin was 1.9 g/dl. Loss of albumin into the stomach and upper small intestine was demonstrated by technetium-99m (99mTc)-albumin scintigraphy. However, no anatomical lesions were found in the gastrointestinal tract. Renal function was normal, urinary protein was minimal, and hepatic function was near normal. A variety of autoantibodies, such as antinuclear antibodies, SS-A, SS-B, or Coombs' antibodies, were detected in serum in association with hypocomplementemia. Immunological studies revealed IgG, IgM, C1q, and C3 deposits in the walls of capillaries in the lamina propria of gastrointestinal mucosae. Combination therapy of prednisolone with an immunosuppressive agent improved the loss of albumin into the bowel and abnormal laboratory findings. This report indicates that the autoimmune process may contribute to the pathogenesis of certain types of protein-losing gastroenteropathy. PMID- 2916533 TI - Tubuloreticular inclusions in colonic mucosa as diagnostic markers of AIDS. AB - Tubuloreticular inclusions (TRI) are known to be associated with viral infections and are considered highly specific of the acquired immune deficiency syndrome (AIDS) in the appropriate clinical setting. We describe a homosexual man without any evidence of AIDS who presented with diarrhea. A search for the usual pathogens was unsuccessful, but electronmicroscopic examination of colonic mucosa revealed numerous tubuloreticular inclusions. The diarrhea subsided and 2 months later the patient developed Pneumocystis carinni pneumonia. This observation suggests that the detection of TRI in the colonic mucosa can precede the clinical manifestations of AIDS, and these structures can be useful markers for the future development of AIDS. PMID- 2916534 TI - Campylobacter pylori and gastric acidity. PMID- 2916535 TI - One-minute test for Campylobacter pylori. PMID- 2916536 TI - Sucralfate therapy for acid-induced upper gastrointestinal tract injury. PMID- 2916537 TI - Peritonitis involving Capnocytophaga ochracea. PMID- 2916538 TI - Response to Drs. Langan and Thomas. PMID- 2916539 TI - Serum triglycerides as an independent risk factor for death from coronary heart disease in middle-aged Norwegian men. AB - The relation between nonfasting serum triglycerides and death from coronary heart disease was studied in 37,546 men aged 35-49 years who were examined during 1972 1977 in four counties in Norway. During an average follow-up period of nine years, 369 deaths from coronary heart disease occurred. In univariate analysis, log(triglycerides) were a weak, but statistically significant predictor of coronary death in the age groups 40-44 and 45-49 years. Within-area analysis showed that a high triglyceride area represented no extreme. When other coronary risk factors were adjusted for, log(triglycerides) remained a significant independent predictor at ages 45-49 years and at higher levels of serum cholesterol. The predictive strength of serum cholesterol was largely the same whether log(triglycerides) were taken into account or not, whereas the predictive strength of log(triglycerides) depended on whether serum cholesterol was accounted for. The strength of coronary death prediction of the logarithm of serum triglycerides was hardly greater than might be explained by the fact that triglycerides are an indicator of the usual cholesterol level of the subject. PMID- 2916540 TI - Cardiovascular risk factor prevention in black schoolchildren: two-year results of the "Know Your Body" program. AB - A five-year intervention study of the effectiveness of the "Know Your Body" program in reducing coronary heart disease risk factors among black students in the District of Columbia, who were in grades 4-6 at baseline, was begun in 1983. Nine schools were stratified on socioeconomic status and randomly assigned to control and intervention groups. The "Know Your Body" curriculum focuses on nutrition, fitness, and the prevention of cigarette smoking. At baseline, 1,234 students were eligible for the screening in which the following target risk factors were measured: systolic and diastolic blood pressures, ponderosity index, triceps skinfold thickness, postexercise pulse recovery rate, serum total and high density lipoprotein (HDL) cholesterol, and serum thiocyanate. After two years of intervention, results indicated that the program may have had a favorable impact on the following risk factors: systolic and diastolic pressures, HDL cholesterol, ratio of total to HDL cholesterol, fitness (postexercise pulse recovery rate), and smoking. Significant net changes in the favorable direction also were found for health knowledge and attitude toward smoking. Blood pressure reduction was associated with decreased ponderosity and improved fitness, and increased HDL cholesterol was associated with decreased ponderosity. These results are consistent with other evaluations of the "Know Your Body" program, suggesting that the program may be effective in reducing chronic disease risk in diverse school populations. PMID- 2916541 TI - The relation of psychosocial dimensions of work with coronary heart disease risk factors: a meta-analysis of five United States data bases. AB - The relation of job psychologic demands and decision latitude to four coronary heart disease risk factors (cholesterol, smoking, and systolic and diastolic blood pressures) was tested among 12,555 men in five investigations conducted in the United States during the period 1959-1980 (National Health and Nutrition Examination Surveys I and II, National Health Examination Survey, Western Collaborative Group Study, and Exercise Heart Survey). Using an imputation strategy, the authors attached measures of the two job characteristics above to persons in each data base by occupation. In 19 possible tests, decision latitude was related (p less than 0.05) to cholesterol and smoking in two instances in the predicted direction in the Exercise Heart Survey, when controlling for Type I error rate. Psychologic demands were not related to any of the risk factors. When a meta-analysis was performed across data bases, all relations were in the predicted direction except for the relation of psychologic demands to systolic pressure, and two of these were statistically significant (p less than 0.05): the relation of job decision latitude to smoking and to systolic pressure. The interaction of psychologic demands and decision latitude was not related to any of the risk factors when two common forms of an interaction were tested. These results indicate that psychosocial aspects of work, in particular the decision latitude of the job, may be related to some cardiovascular risk factors. PMID- 2916542 TI - Occupational strain and the incidence of coronary heart disease. AB - The hypothesis that men in high "strain" occupations have an increased risk of developing coronary heart disease was tested during an 18-year follow-up study from 1965-1983 of a cohort of 8,006 men of Japanese ancestry in Hawaii. There were no significant associations between the incidence of coronary heart disease and the individual job components of high psychologic demands and low job control or for the high strain interaction of these two characteristics. There were, in fact, trends of associations opposite to that predicted by the job strain model which were of borderline significance in multivariate analyses. Stratified analyses by level of acculturation showed similar inverse associations of job strain and coronary heart disease for the more Westernized men and no association for the more traditional men. There were also no significant associations among the various job characteristics and the major risk factors for coronary heart disease in this cohort. The disagreement of these results with those from other studies may be due to methodologic differences of using men whose usual and current occupations were the same in this study compared with using only current occupation in the other studies, the use of different methods of measuring job strain, or the possibility that men in this cohort perceive or react to occupational strain differently. PMID- 2916543 TI - Declining mortality from ischemic heart disease and cerebrovascular disease in Australia. AB - The authors examined the patterns of mortality from ischemic heart disease and cerebrovascular disease in Australia for men and women aged 30-84 years during the period 1950-1986 to assess the relative contributions of period and cohort effects on changes in the mortality rates. Death rates for ischemic heart disease increased from 1950 to the late 1960s and then declined. Although the relative magnitude of the decline was greater among younger age groups, decreasing mortality rates were experienced in all age groups, including the oldest. The period effect was dominant so that each successive cohort experienced lower age specific mortality rates after the late 1960s. Death rates for cerebrovascular disease for both sexes and all age groups have declined since the early 1950s, although the rate of change was less in 1961-1971 and greater before and after this period. No cohort effect was demonstrated for either disease. Changes in diet, decreasing prevalence of cigarette smoking, and increasing treatment of hypertension throughout the period and improved coronary care from the late 1960s onward are all consistent with the mortality trends. PMID- 2916544 TI - Heart disease risk factors, diabetes, and prostatic cancer in an adult community. AB - The authors studied the association between heart disease and prostatic cancer in Rancho Bernardo, California, from August 1972 to June 1987. During a 14-year follow-up of 1,776 men aged 50-84 years, 100 cases of prostatic cancer were identified, of which 54 were incident. Systolic blood pressure, cigarette smoking, and plasma cholesterol levels in cases did not differ from those in noncases. After adjustment for age and on multivariate analysis, incident cases of prostatic cancer had a nonsignificantly higher frequency of reported heart disease at baseline. History of diabetes was inversely associated with total prostatic cancer (age-adjusted estimated relative risk = 0.2, 90% confidence interval: 0.0-0.8; multivariate-adjusted relative risk = 0.3, 90% confidence interval: 0.1-1.0). The association between heart disease and prostatic cancer is compatible with diagnostic detection bias. The inverse association between diabetes and prostatic cancer is compatible with a cancer-promoting role for endogenous testosterone, the level of which is lower in diabetics, or a risk reducing effect of antidiabetic diet or drug therapy. PMID- 2916545 TI - Mammographic parenchymal patterns as indicators of breast cancer risk. AB - Mammographic parenchymal patterns have been suggested as indicators of breast cancer risk. However, few well-controlled studies have used prediagnostic mammograms to determine the pattern classification. The authors studied 266 cases of breast cancer and 301 controls from 25 screening centers of the Breast Cancer Detection and Demonstration Project, a nationwide screening program conducted between 1973 and 1980 to evaluate the risk associated with mammographic patterns using mammograms taken four years before the detection of breast cancer. Mammograms of the cancerous breast of cases and of the ipsilateral breast in the control matched to each case were blindly assessed by one of the investigators (J.N.W.), originator of the mammographic pattern classification. The breast cancer odds ratio among women with the combined P2 + DY patterns, compared with women with the N1 pattern, was 2.8 (95% confidence interval (CI): 1.6-5.1). This estimate of relative risk was comparable with the risk associated with other recognized breast cancer risk factors. The odds ratio among P2 + DY women with a first-degree family history of breast cancer was 5.5 (95% CI: 2.6-11.8) compared with N1 women without a family history. These data provide additional evidence that mammographic patterns are indicators for subsequent development of breast cancer, particularly among women with a first-degree family history of this malignancy. PMID- 2916546 TI - Children, age at first birth, and colorectal cancer risk. Data from the Melbourne Colorectal Cancer Study. AB - During 1980 and 1981, data were obtained on the number of children and age at birth of the first child in 675 cases of colorectal cancer and in 720 age-sex frequency-matched controls as part of a large epidemiologic study of colorectal cancer conducted in Melbourne, Australia. For colorectal cancer, the relative risk (RR) for those with one or more children compared with those with no children was statistically significantly lower than one (RR = 0.61, 95% confidence interval (CI): 0.45-0.81, p less than 0.001), and with simultaneous adjustment for number of children, there was an increasing risk with increasing age at birth of first child (RR = 1.03, with each increasing year of age at birth of first child, 95% CI: 1.00-1.05, p = 0.02). The relation between both the number of children and the age at birth of the first child and colorectal cancer risk was not statistically significantly different for males and females. The risk of colorectal cancer with respect to number of children and age at birth of the first child was unaffected by the potential confounding factors of age, occupation, previous diet, oral contraceptive use in females, and a family history of colorectal cancer. Since the protection against colorectal cancer associated with having children and with earlier age at birth of the first child was found to be similar for both males and females in the Melbourne study, a life style factor, as yet unidentified, rather than a female hormonal factor, is postulated as the mediator of these effects. PMID- 2916547 TI - Epidemiologic evidence on cocaine use and panic attacks. AB - Experienced drug takers and clinicians report that cocaine causes panic attacks. This claim is supported by laboratory evidence on the pharmacologic activity of the drug. In this paper, the authors have used an epidemiologic strategy to examine the suspected cocaine-panic association, with interview data from 5,896 adult household residents sampled in the early 1980s and followed prospectively for a collaborative multisite study of mental disorders in five US metropolitan areas: New Haven, Connecticut; Baltimore, Maryland; St. Louis, Missouri; Durham, North Carolina; and Los Angeles, California. The risk of panic attacks was observed to be greater for identified cocaine users in this sample, as compared with subjects who did not use cocaine during the follow-up interval. The cocaine panic association remained strong after statistical adjustment for preexisting psychiatric conditions, use of alcohol and marijuana, and suspected sociodemographic risk factors for panic attacks. The risk was greatest among cocaine users who reported no marijuana use during the follow-up interval (estimated relative risk = 13.0, 95% confidence interval: 2.24-75.8). The study also identified other determinants for panic attack, including sex, marital status, employment status, job prestige, major depression, and heavy drinking. PMID- 2916548 TI - Report of an illness outbreak at the Harry S Truman State Office Building. AB - An acute epidemic of headache, mucosal irritation, fatigue, odd taste, and dizziness involving several hundred state government employees occurred in June 1986 in an office building in Missouri that housed 2,500 employees. A survey of 305 ill and 131 well employees demonstrated that ill employees were more likely to have perceived unusual odors and inadequate air flow in their work areas. The building has eight floors, seven of which are divided in half by an atrium, and 17 separate air handling systems. A total of 87% of the ill employees were concentrated in only three of the "half floors." Extensive investigation revealed no toxic substances or other direct causes for the illnesses, but several factors were identified that may have reduced air quality in the affected areas. These included a low proportion of outside air, associated with crowding, blocked vents, smoking, and use of office chemicals. This pattern of illness suggests epidemic anxiety state triggered by poor air quality. PMID- 2916549 TI - Sunlight, skin sensitivity, and senile cataract. AB - This study explores the association between sunlight exposure and senile cataract, taking into account such individual differences as skin sensitivity to sunlight and the use of sun-shielding devices, i.e., sunglasses and hats. A case control study was conducted among 160 matched pairs of subjects between October 1, 1984 and June 1, 1985 at the University of Iowa Hospitals and Clinics in Iowa City, Iowa. Cases were selected from among all patients admitted for inpatient or outpatient cataract surgery who were at least 40 years old. Controls were selected from among those waiting for a friend or relative who was attending one of the ophthalmology clinics. Controls were matched to the cases on a 1:1 basis on sex and age (+/- one year). No association was observed between history of sunlight exposure and senile cataract. However, independent of sunlight exposure, the cases with nuclear cataracts reported a more severe acute skin response upon exposure to sunlight for the first time in the summer (a severe burn with blistering) than did their age- and sex-matched controls (McNemar odds ratio (OR) = 1.73, 95% confidence interval (CI): 1.03-2.91). In addition, independent of sunlight exposure, the male controls reported a greater average lifetime use of head coverings in summer which shaded their eyes from the sun than did their age- and sex-matched cases (McNemar OR = 0.48, 95% CI: 0.25-0.94). PMID- 2916550 TI - Poisson regression modeling of temporal variation in incidence of childhood insulin-dependent diabetes mellitus in Allegheny County, Pennsylvania, and Wielkopolska, Poland, 1970-1985. AB - Contradictory observations have accumulated regarding a secular trend and/or an epidemic pattern in the incidence of insulin-dependent diabetes mellitus. In this study, insulin-dependent diabetes mellitus incidence below age 15 years was examined in Allegheny County, Pennsylvania, and in Wielkopolska, Poland, two areas diverse in terms of their geography and average risk for this disease. Numerator data were extracted from individual patient records, and annual denominator data were available for the years 1970-1985. Poisson regression models were used to disentangle the contributions of country, race, sex, age, period, and cohort effects to the observed variation in incidence. Poles and Allegheny County nonwhites were at greatly and moderately reduced risk, respectively, relative to Allegheny County whites. An increase in risk with age was significant and proportional in all three groups. There was significant time variability in Wielkopolska, where an epidemic began in 1982 and continued through 1985. This was a period rather than a cohort phenomenon and was a result of a recent outbreak of the disease rather than a long-term trend. In Allegheny County, changes in risk over the 16-year period were insignificant, although incidence doubled among whites aged 0-9 years during 1982-1983. The Poisson regression modeling provided a quantification and formal comparison of determinants of the incidence of insulin-dependent diabetes mellitus. PMID- 2916552 TI - Central adiposity and gallbladder disease in Mexican Americans. AB - Obesity is widely recognized as a risk factor for gallstones. However, to the authors' knowledge, only one study has examined the effect of body fat distribution on the prevalence of gallbladder disease. Mexican Americans are a population characterized by both a high prevalence of gallbladder disease and an unfavorable body fat distribution. The authors examined whether central adiposity (as measured by the ratio of subscapular-to-triceps skinfold) was related to clinically evident gallbladder disease in 1,202 Mexican Americans and 908 non Hispanic whites in the San Antonio Heart Study from 1979 to 1982. After adjustment for overall adiposity (as measured by body mass index) and the ratio of subscapular-to-triceps skinfold, an increased prevalence of gallbladder disease was still observed in Mexican-American women. Both body mass index and the ratio of subscapular-to-triceps skinfold were positively and independently associated with gallbladder disease in women, while in men, body mass index, but not the subscapular-to-triceps skinfold ratio, was associated with gallbladder disease. Central adiposity is also related to the adverse pattern of cardiovascular risk factors observed in women with gallbladder disease. PMID- 2916551 TI - The increasing incidence of the hemolytic-uremic syndrome in King County, Washington: lack of evidence for ascertainment bias. AB - The annual incidence of the hemolytic-uremic syndrome was determined for the well defined population of King County, Washington, between 1971 and 1986, inclusive, to ascertain temporal trends in the epidemiology of this disease. The average annual incidence rose from 0.69 cases per 100,000 children under age 15 years between 1971 and 1975 to 1.77 cases between 1976 and 1980 and 1.74 cases between 1981 and 1986. The mean hematocrits, platelet counts, and blood urea nitrogen and creatinine concentrations on admission were similar in all periods, as were the mean length of hospital stay and the proportions of patients requiring erythrocyte and/or platelet transfusions and dialysis. These results indicate that the increased incidence of hemolytic-uremic syndrome in childhood has been sustained in King County, Washington, and that this increase is not due to ascertainment bias caused by the diagnosis of less severely ill cases. Further investigations are needed to determine whether this increased incidence is being experienced in other populations and to assess strategies for the prevention of microangiopathic sequelae to hemorrhagic colitis. PMID- 2916553 TI - Effect of human immunodeficiency virus (HIV) antibody knowledge on high-risk sexual behavior with steady and nonsteady sexual partners among homosexual men. AB - For the study of the impact of human immunodeficiency virus (HIV) antibody testing on high-risk sexual behavior with nonsteady and steady sexual partners, 307 homosexual men (118 seronegative, 75 seropositive, and 114 untested) were interviewed at three consecutive six-month intervals between July 1985 and December 1986. From the results, it appears that among seropositives the percentage who performed anogenital insertive intercourse with nonsteady partners remained constant (73, 64, and 61% during the first, second, and third intervals, respectively (nonsignificant]. Among seronegatives and those who were untested, the percentages who practiced anogenital receptive intercourse with nonsteady partners decreased from 44 to 29% and from 54 to 20%, respectively (p less than 0.05). The percentage who performed anogenital insertive intercourse and anogenital receptive intercourse with their steady partner remained constant in all groups: seropositives, +/- 70%; seronegatives, +/- 60%; and untested, +/- 55%. Seropositives were more likely to use condoms during anogenital insertive intercourse with their nonsteady and steady sexual partners than were seronegatives and untested persons during anogenital receptive intercourse with these partners (p less than 0.05). In the majority of cases, condoms were not used antibody testing in the three groups studied. The generalizability of these results, however, is limited. PMID- 2916554 TI - Sociocultural factors in puerperal infectious morbidity among Navajo women. AB - From 1980 to 1982, a sample of 968 pregnant Navajo women in New Mexico was enrolled in a prospective study of biologic and sociocultural factors in puerperal infectious morbidity. Past studies have independently implicated both genital infection and psychosocial stressors in perinatal complications, but, to the authors' knowledge, no previous work has concurrently investigated the interactive effects of genital pathogens and psychosocial processes. Endocervical cultures for Mycoplasma hominis and Chlamydia trachomatis were obtained during prenatal visits, and structured interviews were conducted assessing social support and the degree of cultural traditionality, in this context a proxy measure of acculturative stress. The incidences of postpartum fever, endometritis, and premature rupture of membranes were significantly associated with the concurrence of two factors: the presence of genital tract M. hominis and a highly traditional cultural orientation. When demographic and conventional obstetric risk factors were controlled for, women with both M. hominis and high traditionality experienced infectious complications at a rate twice that of women with either factor alone. Among the plausible explanations for this result is the possibility that acculturative stress undermines physiologic resistance to infectious genital tract disease. PMID- 2916555 TI - A study of the accuracy of cancer risk factor information reported to a central registry compared with that obtained by interview. AB - Sources of readily available data for cancer surveillance are frequently sought. To assess the validity of information on cancer risk factors that is routinely collected in conjunction with cancer incidence reporting, the authors completed interviews for 441 patients identified through the Missouri Cancer Registry from June 1986 to May 1987. Interviews elicited information on employment history, smoking, and alcohol consumption. Data collected from interviews were compared with those previously reported to the Registry by participating hospitals. Exact agreements of three-digit US Census codes were 70% for occupation and 72% for industry. Concordance for never- versus ever-smoking status was 83%, and a high correlation (r = 0.93) was observed for level of smoking. Agreement on alcohol consumption was lower (65%), largely because of the presence of false negatives. Misclassification occurred in a random manner for occupational variables; however, differential misclassification was present for smoking and alcohol histories. Despite the limitations of registry-collected data, these findings suggest that cancer registries that obtain information on cancer risk factors may be suitable for exploratory studies, especially those involving occupational cancer surveillance. PMID- 2916556 TI - Genetic heritability and common environmental components of resting and stressed blood pressures, lipids, and body mass index in Utah pedigrees and twins. AB - The relative contributions of genes and shared environment to cardiovascular risk factors were studied in twins and pedigrees in 1983-1985. Sitting, standing, isometric hand grip, bicycling, and mentally stressed (serial subtraction) blood pressures were obtained from 146 male monozygous twins, 162 male dizygous twins, and 1,102 healthy adults in 67 Utah pedigrees. Fasting total plasma cholesterol, triglycerides, high density lipoprotein cholesterol (HDL), and body mass index were also measured. Heritability was estimated before and after adjusting for 12 environmental variables (measures of socioeconomic status; personality types; exercise levels; use of tobacco, alcohol, coffee, etc.) by using age-adjusted twin intraclass correlations. These heritabilities were compared with those obtained from a variance components analysis of the pedigree data separating genetic and common household effects. Sitting and standing blood pressure heritability estimates were much higher from twin than from pedigree data (39-63% in twins vs. 16-22% in pedigrees), as were those for cholesterol and triglycerides (65 and 75% from twins vs. 42 and 37% from pedigrees) and body mass index (51 vs. 21%). Estimates were similar for heritability of HDL cholesterol (51 vs. 45%). Most of the stressed blood pressure heritabilities were similar to sitting blood pressure estimates. No common household effect (except for adjusted HDL cholesterol (24%), p less than 0.01) was statistically significant for the lipids, blood pressures, or body mass index. Environmental variables correlated much better in monozygous twins and spouses than in dizygous twins, brothers, or sisters. Spouse correlations for lipids, blood pressures, and body mass index were low, with a maximum of 0.12 (p less than 0.05) for HDL cholesterol. We conclude that genes contribute much more than shared environment to the well recognized familial correlation of blood pressures, lipids, and body mass index. PMID- 2916557 TI - Re: "Radiation doses and cause-specific mortality among workers at a nuclear materials fabrication plant". PMID- 2916558 TI - Re: "Validation of work histories obtained from interviews". PMID- 2916559 TI - Advanced Hodgkin disease (clinical stages IIIB and IV): low relapse rate after brief chemotherapy followed by high-dose total lymphoid irradiation. AB - From January 1980 to September 1986, 50 patients with Hodgkin disease, clinical stages (CS) IIIB (26 cases) and IVB (24 cases) were treated by three cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy, followed by high-dose (40 Gy) (sub)total lymphoid irradiation, including the spleen. Ten patients (2 CS IIIB, 8 CS IVB) were in failure, and seven (4 CS IIIB, 3 CS IVB) died during their first complete remission (2 from treatment-related complications, 1 from unknown cause, 4 from insufficient supportive care and/or a shortage of health supplies); three patients (CS IIIB) relapsed (2 alive in second complete remission, 1 deceased). After 7 years, actuarial survival and relapse-free duration were, respectively, 64% for the 50 patients and 89% for the 40 patients in complete remission. Unfavourable outcome was observed in patients with pelvic nodal involvement. The low relapse rate (none in CS IVB) was the most striking result after brief chemotherapy followed by total lymphoid irradiation. PMID- 2916560 TI - Hermansky-Pudlak syndrome: correction of bleeding time by 1-desamino-8D-arginine vasopressin. AB - The effect of the synthetic vasopressin derivative 1-desamino-8D-arginine vasopressin (DDAVP = desmopressin) on bleeding time was studied in three patients with Hermansky Pudlak syndrome. A good response was observed in this type of storage pool disease. DDAVP might be useful in managing the bleeding disorder found in patients with the Hermansky-Pudlak syndrome. PMID- 2916561 TI - Coexistence of myelodysplastic syndrome and untreated chronic lymphocytic leukemia with development of acute myeloid leukemia immediately after treatment of chronic lymphocytic leukemia. AB - A 72-year-old man originally seen for anemia and thrombocytopenia was determined to have chronic lymphocytic leukemia (CLL). Bone marrow examination at the time of CLL diagnosis revealed a small but significant population of atypical blasts. Cytogenetic analysis of the bone marrow aspirate disclosed chromosomal abnormalities (-7, +8) suggestive of a myelodysplastic syndrome. Shortly after treatment of the CLL, there was proliferation of the previously noted blast population, which cytochemical studies demonstrated to be of the myeloid series thus indicating acute myeloid leukemia superimposed on CLL. This report presents microscopic, cytogenetic, immunophenotypic, and cytochemical evidence to document the evolution of acute myeloid leukemia in the bone marrow of a patient with CLL after one course of chemotherapy. PMID- 2916562 TI - Splenic irradiation as primary therapy for prolymphocytic leukemia. AB - A patient with prolymphocytic leukemia (PLL), a lymphoproliferative disorder that carries a poor prognosis, is presented. The disease was diagnosed at an early stage and treatment could be delayed for four years. When massive, painful splenomegaly developed, splenic irradiation (SI) was chosen as the primary form of therapy and an excellent systemic response could be achieved. Our observation is in agreement with preliminary studies, which advocate SI as the primary form of therapy in PLL. Furthermore, it is emphasized that an early diagnosis of PLL is necessary to establish its true course and that the prognosis may be better than originally thought. PMID- 2916563 TI - Modified bleeding time in the infant. AB - The present authors developed a modified template bleeding time for use in the newborn infant. The sensitivity of the bleeding time to the presence of antibiotics, indomethacin, generalized illness, and thrombocytopenia was tested in 242 infants. Both indomethacin and thrombocytopenia similarly prolonged the BT, and the latter could be corrected by raising the platelet count. PMID- 2916564 TI - Seventeen-year survival in multiple myeloma. AB - We report a case of multiple myeloma surviving 17 years since diagnosis and 13 years in continuous complete remission since a relapse 4 years after initial treatment. Despite the prolonged remission, multiple lytic bone lesions have not healed. PMID- 2916565 TI - Safety of regional citrate hemodialysis in acute renal failure. AB - Regional citrate anticoagulation is an alternative to heparin anticoagulation for hemodialysis of patients at increased risk of bleeding. We report the successful use of this technique in 326 dialyses in 49 high bleeding risk patients with acute renal failure. Systemic anticoagulation did not occur as a result of any dialysis procedure, and in no instance was bleeding observed. Dialysis was effective, as judged by removal of creatinine. The safety of this procedure is demonstrated by the lack of bleeding complications and the small incidence of electrolyte and acid-base abnormalities. In addition we document the absence of citrate intoxication by serial measurements of serum citrate levels. Regional citrate anticoagulation is a safe and effective method of performing hemodialysis in patients with acute renal failure at increased risk of bleeding. PMID- 2916566 TI - The protective effect of thromboxane synthetase inhibition on renal function in systemic sepsis. AB - To study the role of thromboxane in systemic sepsis and renal failure, peritonitis was induced surgically in 22 sheep, leading to local and systemic sepsis. A selective thromboxane synthetase inhibitor, U63,557A (Upjohn Co, Kalamazoo, MI) was given before surgery in five animals and 30 minutes after surgery in five animals. A typical picture of volume-loaded, normotensive, vasodilated septic shock developed in all animals. Twenty four hours after induction of sepsis, the control group showed a marked reduction in glomerular filtration rate (GFR), urine volume, and urinary sodium excretion. Pretreated animals showed no change in GFR and a smaller reduction in urine volume and sodium excretion. The posttreatment group showed no change in any parameters of renal function. Plasma renin activity, urinary TXB2 excretion, and urinary 6-keto PGF1 alpha excretion increased after 24 hours only in the control group. Urinary TXB2 excretion was reduced by 80% in animals given U63,557A before surgery. The results indicate a significant protective effect of U63,557A on renal function during septic shock, probably related to reduced thromboxane synthesis, with no apparent deleterious systemic effects. The results support a role for thromboxane in the pathogenesis of acute renal failure in systemic sepsis. PMID- 2916567 TI - No microalbuminuria or other adverse effects of long-standing hyperfiltration in humans with one kidney. AB - Hypertrophy and hyperfiltration are characteristic features of single kidneys and kidneys of patients with insulin-dependent diabetes mellitus (IDDM). In both cases the hyperfiltration has been suggested to be involved in the pathogenesis of renal functional deterioration. We studied the effect of long-standing hyperfiltration on kidney function in 29 subjects with one kidney, three of whom were insulin-dependent diabetics. Four groups were studied: (1) uninephrectomized less than 10 years since uninephrectomy (UN) (n = 7; age, 30 +/- 6 years); (2) uninephrectomized greater than or equal to 10 years since UN (19 +/- 11 years, 10 to 52); n = 14; age, 38 +/- 15 years; (3) congenital unilateral renal agenesis (n = 5, age, 39 +/- 16 years); and (4) IDDM patients with one kidney (n = 3; age, 28 to 52 years; diabetes duration, 8 to 31 years; years with one kidney, 18 to 30). Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by the constant infusion technique, kidney volume (KV) by ultrasonic scanning, and urinary albumin excretion rate (UAE) by radioimmunoassay. In all subjects GFR, RPF, and KV were within the normal range, representing a single kidney hyperfiltration of approximately 70% and hypertrophy of approximately 100%. Only one of the subjects with renal agenesis had an elevated UAE (117 micrograms/min); the remainder had a normal UAE, ie, less than 10 micrograms/min, and the diabetics were below the risk level of 20 micrograms/min. Serum creatinine was normal and BP was slightly elevated in only three subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2916568 TI - Safety and efficacy of low-potassium dialysate. AB - To evaluate the safety and efficacy of low-potassium dialysate, 11 patients with stable end-stage renal disease and with no history of arrhythmia or digitalis use were studied. All were treated with hemodialysis three times per week. Dialysates with potassium concentrations of 2 mEq/L, 1 mEq/L, or 0 mEq/L were compared. Each patient (exceptions noted in text) was studied once at each bath potassium concentration. Cardiac rhythm was recorded by Holter monitor during and for six hours following dialysis. Single PVCs and APCs were common with all potassium concentrations. Only one patient had high-grade ventricular ectopy. It was seen with each of the three potassium concentrations, but was most severe with the potassium-free dialysate. The potassium-free dialysate removed significantly more potassium (78.5 +/- 2.6 mEq) than the 1-K dialysate (62.9 +/- 5.1 mEq) or the 2-K dialysate (50.6 +/- 6 mEq), and the 1-K dialysate removed significantly more potassium than the 2-K dialysate. There were small but significant differences in serum potassium concentrations with the three different dialysates. It was concluded that (1) in all but one of our patients potassium-free dialysate did not produce new ectopy; (2) potassium-free dialysate was 24% more effective than 1-K dialysate and 50% more effective than 2-K dialysate in removing body potassium; and (3) 1-K dialysate was 20% more effective than 2-K dialysate in removing body potassium. PMID- 2916569 TI - Hemolytic uremic syndrome associated with glomerular disease. AB - Secondary hemolytic uremic syndrome (HUS) is uncommon. When it occurs, it is usually in association with pregnancy, malignancy, severe hypertension, drugs, or collagen vascular diseases. It has rarely been reported in patients with glomerular disease. Two such patients with secondary HUS are described. A 17 month-old girl with hematuria and the nephrotic syndrome, negative antistreptolycin O (ASO) titer, and low serum levels of C3 and C4 developed oliguria, progressive azotemia, thrombocytopenia, and microangiopathic hemolytic anemia. A kidney biopsy showed fibrin in glomerular capillaries and cresentic membranoproliferative glomerulonephritis. A 22-year-old man with a 16-year history of relapsing minimal change nephrotic syndrome had been in remission for 5 years when he experienced nephrotic syndrome relapse and developed thrombocytopenia, microangiopathic hemolytic anemia, and renal failure. A kidney biopsy revealed foot process fusion and obstruction of glomerular capillaries with fibrin and platelets. These cases illustrate that HUS can occur in association with other glomerular diseases and should be considered when thrombocytopenia and hemolytic anemia occur in a nephritic or nephrotic patient. PMID- 2916570 TI - Fanconi syndrome with uveitis in an adult woman. PMID- 2916571 TI - Differential diagnosis and pathophysiologic effects of hypercalcemia. PMID- 2916572 TI - Position paper on current status and future needs of pediatric nephrology: training and research. American Society of Pediatric Nephrology. PMID- 2916573 TI - Intradialytic oral feeding and its effect on arterial blood pressure. PMID- 2916574 TI - Computer simulator for determining the single nephron glomerular filtration rate. PMID- 2916575 TI - Gene testing in autosomal dominant polycystic kidney disease: results of National Kidney Foundation workshop. Scientific Advisory Board of the National Kidney Foundation. AB - Until recently the diagnosis of hereditary disorders was dependent on the phenotypic manifestation of those disorders. This created considerable obstacles for effective genetic counseling and family planning in late onset disorders, such as polycystic kidney disease. Moreover, in autosomal dominant disorders there is sufficient clinically variability that diagnosis could not always be established with certainty. For example, in autosomal dominant polycystic kidney disease clinicians were appropriately reluctant to confirm the diagnosis in a 20 year-old, at-risk family member with only a few scattered renal cysts. Moreover, they were equally unwilling to definitively remove any risk of development of the disease from a 20-year-old with normal, noncystic kidneys. Within the last decade, gene linkage and other gene identification techniques have provided new methodologies to surmount these dilemmas. However, these techniques also have produced new questions. In order to provide some guidance to clinicians and investigators utilizing the methodologies of recombinant DNA, genetic linkage, and gene identification the American Society of Genetics commissioned a panel to provide initial guidelines regarding DNA banking. The National Kidney Foundation task force is in agreement with the concepts this group has outlined. However, specific guidelines for the use of genetic linkage techniques in autosomal dominant polycystic kidney disease appeared necessary with the commercial availability of this diagnostic test. PMID- 2916576 TI - Effects of chronic peritoneal dialysis on thyroid function tests. AB - Peritoneal dialysis is associated with large losses of protein. In order to quantify thyroid hormone excretion in the dialysate and to examine the possibility that peritoneal dialysis may result in clinical hypothyroidism, nine endstage renal disease (ESRD) patients undergoing either continuous ambulatory peritoneal dialysis (CAPD) or chronic intermittent peritoneal dialysis (IPD) were studied. Total protein excretion in the peritoneal fluid was 21.5 +/- 2.1 g/24 h and did not vary with the mode of peritoneal dialysis. Thyroid binding globulin (TBG) excretion was 6.4 +/- 1.3 mg/24 h, higher than the values reported in the literature for urinary TBG excretion in patients with the nephrotic syndrome. Despite the higher TBG losses, serum TBG remained in the normal range. Mean peritoneal total T4 and T3 were 8.1 +/- 1.6 micrograms/24 h and 89.5 +/- 14.6 ng/24 h, and there was a significant correlation between peritoneal T4 and TBG (r = 0.69; P less than 0.01) and between peritoneal total proteins and T4 (r = 0.80; P less than 0.001). Despite the finding that large amounts of protein are lost in peritoneal fluid, T4 and T3 losses were relatively modest and remained below their daily production rates, and none of the patients were overtly hypothyroid. Serum thyroid stimulating hormone (TSH) was mildly elevated in three of nine patients and was consistent with early thyroid failure. The patients' serum iodine levels were higher than normal but did not predict the patients' thyroid status. We conclude that major protein losses could predispose patients undergoing CAPD to thyroid failure and that long-term follow-up of thyroid function is warranted in these patients. PMID- 2916577 TI - Tracing the mutations in cystic fibrosis by means of closely linked DNA markers. PMID- 2916578 TI - Linkage disequilibrium, cystic fibrosis, and genetic counseling. AB - Strong linkage disequilibrium occurs between the cystic fibrosis (CF) locus and polymorphisms detected with the DNA probes XV-2c and KM-19. In a North American population, 86% of CF chromosomes occur with a haplotype which occurs on only 14% of normal chromosomes. An individual homozygous for the highest-risk haplotype has an 81-fold greater probability of carrying a CF allele than does an individual homozygous for the lowest-risk haplotype. The linkage-disequilibrium data can be used for prenatal diagnosis and genetic counseling in CF families. The data are useful in 1-in-4-risk pregnancies when DNA is not available from the propositus and in counseling close relatives of CF families. Serious problems arise with some pregnancies which remain at intermediate risks after analysis, and families are left with difficult decisions. It is not clear that genetic testing for couples at less than 1-in-4 risk is cost-effective or standard care, but use of linkage-disequilibrium data will provide more accurate risk probabilities in a substantial proportion of cases if such testing is carried out. Our results emphasize the need for a specific biological or molecular carrier test. This experience in using linkage-disequilibrium and linkage data in combination for genetic counseling provides a model system for the diagnosis of other disorders. PMID- 2916579 TI - Placental mosaicism and intrauterine survival of trisomies 13 and 18. AB - Cytogenetic analysis of 14 placentas from live newborn infants or from terminated pregnancies with trisomies 13 and 18 revealed that all were mosaic. The mosaicism was confined to the cytotrophoblast and not detected in villous stroma, chorionic plate, or amnion. The percentage of cells with a normal karyotype varied from 12% to 100%, the average being 70%. No such confined mosaicism could be detected in 12 placentas of trisomy 21 fetuses. These findings suggest that a postzygotic loss of a trisomic chromosome in a progenitor cell of trophectoderm facilitates the intrauterine survival of trisomy-13 and -18 conceptuses. They also imply that it is placental function which determines the intrauterine survival and that the mother plays no active role in rejection of trisomic conceptions. The combination of both a pre- and post-zygotic cell division defect in viable trisomy-13 and -18 conceptions points to the possibility of a genetic predisposition to such events. The detection of only a diploid cell line in the cytotrophoblast of some pregnancies with trisomies 13 and 18 also suggests that direct preparation is unreliable for prenatal diagnosis of these trisomies on chorionic villi sampling and that long-term villous culture should be used. PMID- 2916580 TI - Gyrate atrophy of the choroid and retina: characterization of mutant ornithine aminotransferase and mechanism of response to vitamin B6. AB - The purpose of this study was to characterize the mutant enzyme in nine patients with gyrate atrophy of the choroid and retina associated with ornithine aminotransferase (OAT) deficiency, to elucidate the mechanism of response to pyridoxine in four pyridoxine-responsive patients, and to determine the extent of genetic heterogeneity in both groups of patients. We have measured the apparent Km for pyridoxal phosphate (PLP) in fibroblast mitochondria and the heat stability of OAT at 45 degrees C in the presence and absence of PLP, using a sensitive radiochemical assay. The apparent Km for PLP was higher in pyridoxine responsive patients than in nonresponsive patients whose apparent Km for PLP was normal. In contrast, the apparent Km for ornithine was normal in the seven patients studied. Surprisingly, the responsive patient with mildest clinical disease had the highest Km for PLP. However, she had the most stable enzyme, which presumably contributed to her milder phenotype. Western blot analyses of mitochondrial proteins, using antibody to human OAT, indicated clearly detectable OAT protein in pyridoxine-responsive patients and in two of five nonresponders, but low or undetectable levels in the other three patients. These data clarify the mechanism of pyridoxine response and indicate heterogeneity within as well as between the pyridoxine-responsive and the nonresponsive patients with gyrate atrophy. PMID- 2916581 TI - Inheritance of ornithine aminotransferase gene, mRNA, and enzyme defect in a family with gyrate atrophy of the choroid and retina. AB - We studied the human ornithine aminotransferase (OAT) gene, mRNA, and enzyme activity in fibroblasts from a family with gyrate atrophy (G.A.) of the choroid and retina, using a normal human OAT cDNA as a probe. The family consists of an affected patient, who is heterozygous for a partial deletion of the functional OAT gene and whose cells produce no mRNA, and of his father, mother, two sons, and a daughter. Southern blot analysis of the OAT gene showed the partial deletion in the patient and in his father and daughter and in one son. Northern blot analysis revealed no OAT mRNA in the patient and approximately 50% of the normal level of OAT mRNA in the father, mother, two sons, and daughter. Assay showed that the OAT activity in these individuals mirrored the OAT mRNA levels. The results indicate that an active allele of the OAT gene expresses 50% of the total normal OAT mRNA and activity and that both alleles of the gene are inactive in the patient in this pedigree, a situation resulting in a complete absence of the OAT mRNA, in accordance with the autosomal recessive mechanism of this disease; they also indicate a 50% decrease of OAT mRNA and enzyme activity in obligate heterozygous carriers carrying one defective allele and that these defects are stably inherited. PMID- 2916583 TI - Evidence for an elevated frequency of in vivo somatic cell mutations in ataxia telangiectasia. AB - Somatic cell mutation frequency in vivo was measured in individuals with high cancer risk who were from ataxia telangiectasia (A-T) families. The assay for somatic mutation measures the frequency of variant erythrocytes which are progeny of erythroid precursor cells with mutations that result in a loss of gene expression at the polymorphic glycophorin A (GPA) locus. Samples from 14 of 15 A T homozygotes showed high frequencies of GPA gene expression-loss variant cells with normal expression of only one of the two alleles at the GPA locus (i.e., GPA hemizygous variant cells). The mean elevation of the frequency of hemizygous variant cells over those in normal controls and unaffected family members was 7 14-fold. A-T homozygotes also showed an increase in the frequency of cells in which one allele at the GPA locus had lost expression and in which the remaining allele was expressed at a homozygous level (i.e., GPA homozygous variant cells). Family members who are obligate A-T heterozygotes did not appear to have a significantly elevated frequency of GPA hemizygous or homozygous variant cells. These indications of elevated in vivo frequencies of variant erythrocytes in A-T homozygotes support a causal link between susceptibility to somatic mutation and susceptibility to cancer. PMID- 2916584 TI - Km1 allotype association with one subgroup of alopecia areata. AB - The distribution of the immunoglobulin kappa light-chain determinant, Km1, was examined in 52 patients with alopecia areata, 22 of whom possessed serum antibodies to thyroid antigens. The allotype frequency was significantly higher than that found in a referent population of 105 healthy subjects. Furthermore, it was determined that within the patient population, the Km1 allotype was associated with the absence of detectable serum autoantibodies. In such patients, this association may be due to linkage disequilibrium between the chromosome 2 gene coding for Km1 and a chromosome 2 gene coding for susceptibility to alopecia areata. PMID- 2916582 TI - Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction. AB - Interspersed DNA elements of the form (dC-dA)n.(dG-dT)n constitute one of the most abundant human repetitive DNA families. We report that specific human (dC dA)n.(dG-dT)n blocks are polymorphic in length among individuals and therefore represent a vast new pool of potential genetic markers. Comparison of sequences from the literature for (dC-dA)n.(dG-dT)n blocks cloned two or more times revealed length polymorphisms in seven of eight cases. Variations in the lengths of 10 (dC-dA)n.(dG-dT)n blocks were directly demonstrated by amplifying the DNA within and immediately flanking the repeat blocks by using the polymerase chain reaction and then resolving the amplified DNA on polyacrylamide DNA sequencing gels. Use of the polymerase chain reaction to detect DNA polymorphisms offers improved sensitivity and speed compared with standard blotting and hybridization. PMID- 2916586 TI - Advanced cardiovascular therapy: redefining clinical goals-- therapy and protection across the ischemic spectrum. St. George, Bermuda, April 15, 1988. Proceedings. PMID- 2916585 TI - Heritability of bone mass: a longitudinal study in aging male twins. AB - Midshaft radial bone mass was first measured from 1970 through 1972 by photon absorptiometry in 42 pairs of monozygotic (MZ) and 38 pairs of dizygotic (DZ) male Caucasian twins (age 44-55 years). The MZ intraclass correlation (rMZ) of .70 was significantly larger (P less than .05) than the DZ correlation (rDZ) of .45, providing evidence for genetic influences (Smith et al. 1973). Radial bone mass measurements repeated 16 years later (1986-87) on 25 of the MZ pairs and on 21 of the DZ pairs revealed an rMZ of .61 and an rDZ of .44, but the difference was not significant (P greater than .05). The twins had an average radial mass loss of 0.49%/year between the two examinations. The rMZ (.52) and rDZ (.49) values for the 16-year loss in radial mass were both significantly different from zero, but their similar size indicated that the correlations were due to nongenetic factors. In a search for the source of genetic influences on adult radial mass, heritability was estimated by the formula 2(rMZ - rDZ) for radial width and was found to be .66 and .76 (P less than .05) for examinations 1 and 2, respectively. An index of radial density (mass/width) was calculated, and the differences between rMZ and rDZ were not significant at either examination. The intraclass correlations (rMZ = .35; rDZ = .43) were both significant for the loss of bone density between examinations but provided no evidence for genetic influences, results similar to the findings for the loss of mass.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2916587 TI - Total ischemic burden. Implications for prognosis and therapy. AB - Patients with silent myocardial ischemia can be classified as one of three clinical types: those who are totally asymptomatic (type 1), those who are asymptomatic after a myocardial infarction (type 2), and those who demonstrate both asymptomatic and symptomatic episodes (type 3). Total ischemic activity may be similar in any given patient, but the ratio of symptomatic to asymptomatic episodes will differ. Prognosis appears dependent on the degree of total ischemic activity plus the extent of coronary artery disease and left ventricular dysfunction. The effects of therapy can be monitored with exercise testing and/or Holter monitoring. Using the latter technique, the largest multicenter study to date, the Nifedipine Total Ischemia Awareness Program, has demonstrated the advantages of adding a calcium antagonist to nitrate and/or beta-blocker therapy regimens in order to maximize the reduction in total ischemic activity in angina patients. PMID- 2916589 TI - The gang that couldn't listen straight. PMID- 2916588 TI - Silent myocardial ischemia. Mechanisms and rationale for therapy. AB - The widespread use of Holter monitoring has demonstrated that the majority of ischemic episodes occur during activities that do not require exertion. These episodes tend to occur at only minimal increases in heart rate above resting levels, well below the level of myocardial oxygen demand required to produce ischemia on formal exercise tolerance testing. In all likelihood, therefore, most ischemic events in ambulatory patients are due to a combination of flow-limiting coronary stenosis and superimposed vasoactive or thrombotic elements. Asymptomatic ischemic events are common in subsets of patients with angina pectoris. Traditionally, treatment with calcium channel blockers, beta-blockers, and long-acting nitrates has been aimed at reducing episodes of angina pectoris. Despite a reduction in anginal symptoms, however, it is likely that patients continue to experience silent ischemia, particularly at rest and during activities of daily living. The strategy for treatment in such patients should include the abolition of the patients' "total ischemic activity." It is conceivable that more aggressive anti-ischemic therapy may improve prognosis, as patients with ambulatory ST-segment depression experience frequent cardiac events. Other potential benefits of more aggressive treatment include the prevention of myocardial hibernation, which occurs as a result of a chronic ischemic state, and a reduction in episodes of myocardial stunning. This approach may lead to protection against transient and chronic left ventricular dysfunction, which is associated with a poor prognosis in patients with symptomatic coronary artery disease. PMID- 2916590 TI - Some herbal teas can be toxic. PMID- 2916591 TI - Shopping for liability insurance. PMID- 2916592 TI - Forensic nurse examiners. PMID- 2916593 TI - Lithium. In a class by itself. PMID- 2916594 TI - Handle with care. PMID- 2916595 TI - Monitoring uterine activity at home. PMID- 2916597 TI - A new way to size up a wound. PMID- 2916596 TI - Five years of fewer falls. PMID- 2916598 TI - People without land. PMID- 2916599 TI - Arrhythmia or artifact? PMID- 2916600 TI - Demented, old, and alone. PMID- 2916601 TI - Listening with care. PMID- 2916602 TI - California jobfocus. California: with a special section on the western Sunbelt. PMID- 2916603 TI - Research on every rung of the clinical ladder. PMID- 2916604 TI - A capitol day. Power and politics 101. PMID- 2916605 TI - A handy software checklist. PMID- 2916606 TI - Unexpected miracles. PMID- 2916607 TI - Intrapartum fetal heart rate patterns in pregnancies complicated by hypertension. A cohort study. AB - Intrapartum fetal heart rate patterns were investigated in pregnancies complicated by hypertension in a cohort study. The total number of live births was 2400 and the frequency of hypertension was 8.8%. The study group comprised 2023 normotensive and 200 hypertensive deliveries. Dates of all pregnancies were established at an ultrasound examination in week 17. Ominous intrapartum fetal heart rate patterns were significantly more common in hypertensive deliveries than in normotensive deliveries (20.5% versus 7.6%). The women with hypertension were compared with a group of control women matched for age, parity, induction of labor, and gestational week (20.5% versus 6.5%). In hypertensive women ominous fetal heart rate tracings were frequently associated with primiparity, induced labor, epidural block, delivery of a growth-retarded fetus, and beta 1-adrenergic receptor blockers. Ominous fetal heart rate patterns were less common in hypertensive women without these risk factors; still the significant differences in comparison with normotensive women remained. The hypertensive pregnancies accounted for no less than 21.0% of all ominous intrapartum fetal heart rate patterns, whereas 13% of all cases of ominous intrapartum fetal heart rate patterns could be attributed to the excess frequency in hypertensive pregnancies. PMID- 2916609 TI - Association of episiotomy and delivery position with deep perineal laceration during spontaneous delivery in nulliparous women. AB - Spontaneous deliveries of 241 nulliparous women were analyzed to test the hypothesis that both episiotomy and use of stirrups for delivery of infants were related to the occurrence of third- and fourth-degree perineal lacerations. These deep perineal tears occurred in 0.9% of the women delivered of infants without the use of either episiotomy or stirrups and in 27.9% of the women delivered of infants with both episiotomy and stirrups. Women exposed to episiotomy alone or to stirrups alone had intermediate rates of laceration. There was no independent correlation of laceration with maternal age, 1- and 5-minute Apgar scores, or midwife or physician as delivery attendant. The results suggest that selective use of episiotomy and stirrups can minimize perineal trauma during spontaneous delivery in nulliparous women. PMID- 2916608 TI - Fetal organ and xenograft transplantation. AB - The use of anencephalic fetuses and neonates as organ donors is technically feasible, and xenografts may be. Several ethical questions emerge, however, involving the appropriate use of such organs and what alterations, if any, in obstetric and neonatal management may be acceptable to increase the availability and likelihood of success of such organs. PMID- 2916610 TI - Evaluation of the new amniostat-FLM test for the detection of phosphatidylglycerol in contaminated fluids. AB - The Amniostat-FLM rapid slide test (Hana Biologics, Inc., Alameda, Calif.) for detection of phosphatidylglycerol has previously been evaluated and has shown good correlation with the more sophisticated two-dimensional thin-layer chromatographic method. A new, ultrasensitive kit has now been released with a lower level of detection of 0.5 microgram of phosphatidylglycerol per milliliter of fluid. This is the first report of this new kit, which we used with vaginal pool samples and with contaminated amniocentesis samples. We evaluated this kit for concordance with thin-layer chromatography results as well as fetal outcome. Of 48 vaginal pool samples, 41 (85%) showed concordance, whereas 39 of 42 (93%) contaminated amniocentesis samples were concordant, for an overall concordance of 89% (80 of 90 samples). Sixty-seven infants were delivered within 72 hours of the test and there were no cases of hyaline membrane disease in the presence of a positive test result. We conclude that this new, ultrasensitive kit is a good, time-saving, and reliable test for the detection of phosphatidylglycerol without the development of false-positive results even when tested on the worst possible fluid samples. A review of clinical studies involving the Amniostat-FLM is also presented. PMID- 2916611 TI - Format of an obstetrics and gynecology journal club and four years' experience. AB - Departmental journal clubs have experienced varied degrees of success and longevity. Although a high degree of enthusiasm is difficult to maintain, clear objectives are key factors that encourage active participation. In this report we present a journal club format that has demonstrated popularity and 4 years of longevity. On the basis of this experience, we believe a journal club forum offers medical students and residents the optimal opportunity to learn an approach to critical reading of medical reports. In addition, they gain understanding of experimental design and research protocols and ultimately acquire knowledge of the current medical literature. PMID- 2916612 TI - Antibody to endotoxin is associated with decreased frequency of postoperative infection. AB - According to previous studies the presence of preoperative antibodies to gram negative lipopolysaccharides has a protective effect against postoperative infection and pyrexia in patients undergoing urologic and cardiac surgical procedures. Preoperative serum specimens collected from 86 women awaiting major gynecologic surgery were tested for the presence of antiendotoxin by a qualitative method. These patients were closely followed up in the postoperative period and any evidence of pyrexia or infection was noted. There were 21 (24%) patients who had preexisting antibodies. Of the women studied, 47 (55%) had some form of postoperative infection, of which 32 (37%) were exclusively a result of gram-negative bacteria. There was a significant association (p less than 0.05) between postoperative infection and the absence of preexisting antibodies. This association was particularly striking (p less than 0.02) when postoperative urinary tract infections were considered. There was no association between postoperative pyrexia and the absence of preexisting antibody. Our results confirm the findings of previous studies to evaluate the protective role of antiendotoxin in surgical procedures. In the future immunization may be considered an adjunct or alternative to prophylactic antibiotics. PMID- 2916613 TI - Fetal control of maternal prolactin production and bioactivity in utero. AB - Amniotic fluid prolactin is a product of maternal decidualized endometrium that is derived by translocation of the hormone across the reflected fetal membranes. Amniotic fluids from 26 second-trimester (14 to 23 weeks) and 75 third-trimester (29 to 40 weeks) normal singleton pregnancies were evaluated for prolactin content by radioimmunoassay and bioassay with the Nb2 rat lymphoma cell line. The relative bioactivity was calculated as the ratio of bioassay to radioimmunoassay for each fluid. Data segregated by gestational age and fetal genetic sex identified a highly significant difference (p = 0.0004) in amniotic fluid prolactin radioimmunoassay concentrations (mean +/- SEM) that surround male (682 +/- 49, n = 42) versus female (440 +/- 39, n = 33) fetuses of third-trimester age. Paired bioassay values were significantly lower (p = 0.002) than radioimmunoassay values among males (626 +/- 52) but equivalent (p = 0.1066) among females (464 +/- 44). The bioassay/radioimmunoassay ratios of third trimester fetal female-associated amniotic fluid prolactin were significantly higher (p = 0.0004) than those of third-trimester males and second-trimester males and females. The results suggest a fetal gender-related factor is associated with both the production and the biologic activity of the maternally derived hormone. Thus the fetus appears to have some control over the dynamics of uterine prolactin production. PMID- 2916614 TI - Child sexual abuse--genital tract findings in prepubertal girls. I. The unaided medical examination. AB - In a prospective study 205 prepubertal girls (mean age, 5.4 years) determined by Child Protective Services to be victims of sexual abuse were examined. Sixty-five girls (32%) had normal-appearing genitalia, 45 girls had nonspecific findings, and 95 girls had findings considered to be specific for sexual abuse. Whereas normal-appearing genitalia were most often observed in girls reporting digital assault, specific findings were more commonly observed in girls reporting genitogenital assault. Overall it was possible to document the presence of abnormal genital findings indicating or strongly suggesting sexual abuse in only 46% of the patients in this study group. Failure to document findings suggestive of abuse in half of the girls highlights the limitations of the medical evaluation in validating sexual abuse. PMID- 2916615 TI - Child sexual abuse--genital tract findings in prepubertal girls. II. Comparison of colposcopic and unaided examinations. AB - In recent years the inspection of the vulva of sexually abused girls by magnification with a colposcope has become increasingly popular. However, data concerning the usefulness of colposcopy in such evaluations are lacking. In a prospective study, 130 prepubertal girls (mean age 5.5 years) who were identified by child protective agencies to be victims of sexual abuse were evaluated both by an unaided examination and by colposcopy. If the colposcopic findings differed from those of the unaided inspection, the macroscopic examination was repeated to determine whether the abnormality could have been detected without magnification. Altogether, 92 of the 130 girls were found to have abnormal findings. In the majority of girls with abnormalities (96%), the abnormalities were observed during the unaided examination. Of the four patients in whom the findings were detected initially by the colposcopic examination, these findings were observed during the repeat unaided examination. The findings were observed by colposcopic examination alone in only one patient. We conclude that unaided examination is adequate for the evaluation of most victims of sexual abuse. PMID- 2916617 TI - Change of immunoglobulin G antibody levels to Toxoplasma gondii during pregnancy in an obstetric population. AB - Paired sera obtained from 393 pregnant women during the first trimester and from their umbilical cords at birth were examined for immunoglobulin G antibodies to Toxoplasma gondii by enzyme-linked immunosorbent assay. The course of antibody levels in asymptomatic populations is discussed with regard to possible fetal infection during the gestational period. PMID- 2916616 TI - An evaluation of red blood cell heterogeneity (increased red blood cell distribution width) in iron deficiency of pregnancy. AB - A new classification of anemias, which is based on mean corpuscular volume and quantitative anisocytosis (red blood cell distribution width), was evaluated in 331 pregnant women on initial presentation for prenatal care. Seventy-four of them had severe iron depletion (serum ferritin level less than or equal to 10 ng/dl). Contrary to the above classification, early iron deficiency without anemia was infrequently identified by an increase in distribution width (4 of 25 patients). The distribution width was not consistently increased in the 49 anemic, iron-deficient patients; 34 were normal and would have been considered to have thalassemia minor or anemia of chronic disease according to the new classification. The distribution width was no more sensitive than the mean corpuscular volume in suggesting iron deficiency. This study does not confirm the usefulness of the new classification in the diagnosis of iron deficiency in this patient population. PMID- 2916618 TI - Congenital hereditary fructose intolerance and pregnancy. AB - Congenital hereditary fructose intolerance is associated with the inability to tolerate fructose and carbohydrates, which are converted into fructose. We describe management of a pregnancy complicated by this disease in the mother and its implications for the neonate. PMID- 2916619 TI - Obstetric outcome of patients with more than one previous cesarean section. AB - Records of patients with more than one previous cesarean section were reviewed for a 1-year period. Of 69 such pregnancies, 36 underwent trial of labor in concurrence with an ongoing departmental cesarean section reduction initiative; 80% culminated in vaginal delivery. Twenty of these 69 patients had three or more previous cesarean sections; 9 underwent trial of labor, with 8 subsequent vaginal deliveries. The vaginal delivery rate after more than one previous cesarean section was no different from that of patients with only one previous cesarean section. We conclude that trial of labor in patients with more than one previous cesarean section did not result in a deleterious outcome. Our findings suggest that a trial of labor after more than one previous cesarean section delivery can safely be allowed. Guidelines can be identical to those already established for patients with only one previous cesarean section. PMID- 2916620 TI - Human fetal ductal flow velocity waveforms relative to behavioral states in normal term pregnancy. AB - In 16 normal pregnancies the relationship between the blood flow velocity waveform and fetal behavioral states at 37 to 38 weeks' gestation was studied. Whereas behavioral state independency was established for the acceleration time, peak flow velocity demonstrated a statistically significant reduction during active sleep, compared with quiet sleep. These data reflect reduced ductal flow and suggest a redistribution in the left-ventricular and right-ventricular output in favor of the left side of the heart during active sleep. Peak flow velocities in the fetal ductus arteriosus were independent of fetal heart rate. PMID- 2916621 TI - Measurement error in clinical perinatal data. AB - The error measurement of clinical perinatal variables obtained during the standardization and data-collection periods of a large prospective epidemiologic study is presented. The error is considerably larger during the data-collection period, particularly with regard to uterine height, birth weight, and blood pressure values. This information strongly supports the need to continuously supervise and monitor perinatal data collection systems, even after standardization. PMID- 2916622 TI - Diagnosis of gestational diabetes by use of a glucose polymer. AB - The oral glucose tolerance test is the recommended method for the assessment of carbohydrate metabolism in pregnancy. However, available glucose drinks are often associated with varying degrees of gastrointestinal symptoms that might preclude meaningful studies. Polycose (Ross Labs, Columbus, Ohio) is a glucose saccharide polymer mixture containing 3% glucose, 7% maltose, 5% maltotriose, and 85% polysaccharide of 4 to 15 glucose units, with an osmotic load one fifth that of glucose. We assessed the efficacy of this glucose polymer in the performance of a 3-hour carbohydrate tolerance test with glucose and glucose polymer used 3 to 5 days apart in each patient tested. After 2 days of 300 gm carbohydrate-enriched diets, 48 patients underwent 3-hour carbohydrate tolerance tests at a mean gestational age of 30 +/- 3 weeks. Statistical analysis revealed a moderate level of agreement (kappa = 0.45, p less than 0.001) between the results of both carbohydrate tolerance test preparations. Patients experienced fewer gastrointestinal symptoms with the glucose polymer than with glucose. These preliminary data suggest that glucose polymer may be effectively used in the performance of a 3-hour carbohydrate tolerance test. PMID- 2916623 TI - Blood glucose and oxygen tension levels in small-for-gestational-age fetuses. AB - Blood glucose and oxygen tension levels were measured in umbilical venous and arterial samples obtained by cordocentesis from 63 small-for-gestational-age fetuses. Reference ranges for these parameters were established by measurement of blood glucose (n = 122) and oxygen tension (n = 189) levels in appropriate-for gestational-age fetuses that were undergoing cordocentesis in the prenatal diagnosis of congenital abnormalities. The fetuses were subsequently found to be unaffected by the condition investigated. In the small-for-gestational-age fetuses, the maternal-to-fetal blood glucose concentration gradients for the umbilical vein and artery correlated significantly with the degree of fetal hypoxia but not with the degree of fetal smallness. Furthermore, there was no significant difference in the relationship of maternal and fetal blood glucose concentration gradient and hypoxia between the umbilical venous and arterial samples, which suggests that the major cause of hypoglycemia in small-for gestational-age fetuses is reduced supply rather than increased fetal consumption or decreased endogenous production of glucose. PMID- 2916624 TI - A prospective New Zealand study of fertility after removal of copper intrauterine contraceptive devices for conception and because of complications: a four-year study. AB - A prospective New Zealand study was started in 1982 to determine fertility rates and pregnancy outcomes after removal of copper intrauterine contraceptive devices to allow conception or because of complications. In a combined 4-year study, there were 887 removals to allow conception and 164 due to complications. Participants were 375 (35.7%) nulligravid and 676 (64.3%) gravid women. Within 48 months, 91.5% of the nulligravid and 95.7% of the gravid women had conceived. A 2 year combined study, with regard to longer use of intrauterine contraceptive devices (greater than 2 years), did not show any significant reduction in fertility or increase in ectopic gestation within 24 months. However, in gravid women of similar age distribution, there was a significant increase in the miscarriage rate, compared with use of intrauterine contraceptive devices for less than 2 years or compared with nulligravid women. In a 1-year study, removals because of complications did not cause a significant reduction in fertility or an increase in ectopic gestation, miscarriage, or preterm delivery rates within 12 months, compared with removals to allow conception. PMID- 2916625 TI - Oral contraceptive use and the risk of chlamydial and gonococcal infections. AB - Oral contraceptive users were compared with nonusers with respect to the rate of cervical infections by Chlamydia trachomatis and Neisseria gonorrhoeae. The comparison was adjusted for differences in demographic and behavioral characteristics between the two groups. The rates of infection among oral contraceptive users were increased by approximately 70% (statistically significant) for both pathogens. Cervical ectopy was implicated in the increased rate of chlamydia but not gonorrhea. Rates of gonorrheal infection differed significantly among oral contraceptive formulations; rates were higher for formulations containing more androgenic progestins. PMID- 2916626 TI - Long-term oral contraceptive use does not affect trabecular bone density. AB - To determine whether long-term exposure to exogenous estrogen in oral contraceptives influences trabecular bone mass in premenopausal women, we studied 25 closely matched, healthy, premenopausal women, who were recruited from an active obstetrics and gynecology practice. Eleven women had never used oral contraceptives, and 14 women had used oral contraceptives for a minimum of 67 months. All oral contraceptive users had used preparations that provided a minimum of 50 micrograms mestranol per day. Trabecular bone density was determined by quantitative single-energy computerized tomography of the L1-3 lumbar vertebral bodies. Trabecular bone density was similar for both the control group and the oral contraceptive users, 160.6 +/- 6.9 versus 161.2 +/- 7.4 mg/ml, respectively. The power to detect a 15% difference in bone density between these two samples was 0.87. We concluded that long-term, premenopausal oral contraceptive use has no effect on vertebral bone density. PMID- 2916627 TI - Management of the third stage of labor in pregnancies terminated by prostaglandin E2. AB - In the management of second-trimester medical terminations of pregnancy, it is a commonly accepted practice to allow 2 hours for the third stage of labor. This practice is based on data from terminations with saline solution as the abortifacient. Herein we report our experience with the use of prostaglandin E2 vaginal suppositories for midtrimester terminations, with particular regard to placental delivery rates and associated complications. Ninety-six patients underwent prostaglandin E2 vaginal suppository terminations. Fifty-eight percent of patients had spontaneous placental delivery within 2 hours of the passage of the fetus; approximately two thirds of these were expelled within 30 minutes. Previous work involving elective saline solution-induced terminations suggested the 2-hour time limit for the third stage of labor. This was based on an unacceptable complication rate of greater than 4% beyond 2 hours. The present study of the use of prostaglandin E2 suppositories for a variety of indications demonstrated a similar complication rate of 4% at 30 minutes. These findings suggest expectant management beyond this time limit may produce unacceptably high complication rates. PMID- 2916628 TI - Acute pericarditis complicated by cardiac tamponade during pregnancy. AB - A case of acute pericarditis, complicated by pericardial effusion and cardiac tamponade, is described. PMID- 2916629 TI - Coitus, twin pregnancy, and preterm labor. AB - The effect of coitus on precipitation of preterm labor was studied prospectively in 126 women with twin pregnancies. All of the women attended a special antenatal clinic in a tertiary referral center and were questioned about the frequency of coitus. Of the participants, 40% reported coitus early in the third trimester; the rate decreased to 24% by 36 weeks' gestation. There were no significant differences in the frequency of positive responses between those who went into labor before term when contrasted with those who were delivered of infants at term. The data indicate that coitus is not an important precipitant of preterm labor in this high-risk group and that coitus need not be discouraged in women with twin pregnancies. PMID- 2916630 TI - Factors influencing hemostasis after umbilical vein puncture in vitro. AB - Bleeding from the site of cordocentesis can be detected by ultrasound examination, but significant hemorrhage into the amniotic fluid rarely occurs. To evaluate the relative contribution of amniotic fluid thromboplastins and the quantity of Wharton's jelly in facilitating coagulation at the puncture site, amniotic fluid samples and umbilical cord segments were obtained at cesarean section from 20 patients. After puncture of the umbilical vein, bleeding times were measured in amniotic fluid and 0.9% sodium chloride. The quantity of Wharton's jelly was assessed by measuring umbilical cord circumference. Mean bleeding times were significantly shorter in amniotic fluid compared with saline solution, but there was no consistent relationship between bleeding times and umbilical cord circumference. We conclude that properties of amniotic fluid facilitate coagulation at the site of umbilical vein puncture. PMID- 2916631 TI - Amnionitis and life-threatening respiratory distress after percutaneous umbilical blood sampling. AB - Although amnionitis secondary to percutaneous umbilical blood sampling is extremely uncommon, a high index of suspicion should be maintained and a full evaluation should be initiated if nonspecific signs of infection appear within 2 weeks after the procedure is performed. In this case life-threatening adult respiratory distress syndrome was a sequela of this complication. PMID- 2916632 TI - Angiographic embolization of intractable puerperal hematomas. AB - Puerperal hematomas may not respond to conventional therapy, including vaginal packing, drainage, and hypogastric artery ligation. Two cases are presented in which selective angiographic arterial embolization was used to manage this potentially lethal complication. PMID- 2916633 TI - Prednisone does not prevent recurrent fetal death in women with antiphospholipid antibody. AB - Effects of therapy, antibody titer, and pregnancy history on pregnancy outcome were evaluated in pregnancies of women with antiphospholipid antibody. Prior fetal death and a high antiphospholipid antibody titer (greater than 40 IgG phospholipid units) contributed independently, in an additive manner, to current fetal loss. Twenty-one pregnancies occurred in asymptomatic women who had both prior fetal death and a high IgG antiphospholipid antibody titer. In this very high-risk group, 9 of 11 (82%) of pregnancies treated with prednisone, 10 to 60 mg/day, ended in fetal death, compared with 5 of 10 (50%) not treated with prednisone (p approximately 0.01, life-table analysis). Of pregnancies treated with aspirin, 80 mg/day, 9 of 14 (64%) treated and 5 of 7 (71%) not treated with prednisone had a fetal death (difference not significant). Prednisone does not improve, and may worsen, current fetal outcome in asymptomatic pregnant women with a high antiphospholipid antibody titer and prior fetal death. PMID- 2916634 TI - Unsuccessful Burch retropubic urethropexy: a case-controlled urodynamic study. AB - A retrospective comparison was made of the urodynamic parameters of urethral sphincteric function of 21 women with failure of modified Burch retropubic urethropexy and 21 matched control subjects in whom operation was successful. The match criteria included multiple risk factors that contributed to the failure of antiincontinence surgery. The preoperative resting urethral closure pressure and urethral functional length were significantly lower in the study (failure) group than in the control (success) group. These parameters of intrinsic urethral function improved only in the control (success) group after operation. Further study showed that 17 of the 21 patients (81%) in the control (success) group had preoperative closure pressure greater than 20 cm H2O, whereas only five of the 21 patients (24%) in the study (failure) group had initial closure pressure higher than this value. Identification of a low-pressure urethra by preoperative urethral profilometry suggests a greatly increased risk for operative failure. PMID- 2916635 TI - Intravenous clonidine hydrochloride toxicity in pregnant ewes. AB - Administration of intravenous clonidine hydrochloride has been advocated to rapidly control blood pressure in severe preeclampsia. To examine clonidine's acute maternal and fetal effects were intravenously injected 300 micrograms clonidine in eight chronically prepared normotensive near term ewes. Unlike intravenous saline solution injection, clonidine produced significant toxicity- intraamniotic pressure increased 97 +/- 27% (p less than 0.05), uterine blood flow decreased 55 +/- 7% (p less than 0.001), maternal and fetal serum glucose increased 158 +/- 23% and 249 +/- 91%, respectively (p less than 0.001), and maternal and fetal Po2 decreased to 44 mm Hg +/- 4 mm Hg and 13 mm Hg +/- 1 mm Hg, respectively (p less than 0.05). Maternal and fetal blood pressure and serum cortisol were unaffected by clonidine, whereas heart rate decreased. No adverse maternal or fetal effects were noted with serum clonidine concentrations less than 1.0 ng/ml. Direct fetal infusion of clonidine did not lower fetal arterial Po2 levels, although heart rates decreased and serum glucose levels increased. The multiple effects of clonidine infusion are best explained by actions on alpha 2-adrenergic receptors. These results suggest that intravenous administration of clonidine may adversely affect the fetus by direct actions and by alterations in maternal physiology. PMID- 2916636 TI - Labetalol does not decrease placental perfusion in the hypertensive term-pregnant rat. AB - The acute effect of labetalol hydrochloride, a combined nonspecific beta adrenergic and postsynaptic alpha 1-adrenergic blocker, on maternal hemodynamics and organ perfusion was investigated in 10 hypertensive, term-pregnant, spontaneously hypertensive rats with the use of the radioactive-labeled microsphere technique. The normal fall in blood pressure during pregnancy was prevented by the reduction of litter size to two conceptuses on day 7 of gestation. Labetalol (1 to 6 mg/kg) effectively lowered mean arterial pressure 22% by decreasing cardiac output 16%; total peripheral resistance was not significantly decreased. Thus, the blood pressure lowering effect of labetalol was due primarily to its beta-adrenergic blocking effect. Regional flows to the carcass and splanchnic circulation were decreased 19% and 15%, respectively, after labetalol administration. Uterine wall and ovarian perfusion were significantly reduced, but placental perfusion was not significantly altered. Because labetalol lowers blood pressure without reducing placental perfusion, it may be a useful alternative to hydralazine for the treatment of hypertensive emergencies in pregnancy. PMID- 2916637 TI - Neodymium:yttrium-aluminum-garnet laser occlusion of rhesus placental vasculature via fetoscopy. AB - We tested the feasibility of photocoagulating placental vascular communications with a fetoscopically delivered neodymium:yttrium-aluminum-garnet laser in 12 pregnant monkeys in the second trimester. The technique was successful in eight cases. One ended in spontaneous labor 2 weeks after occlusion and one stillbirth occurred at term. Six live fetuses were delivered at term, with all treated vessels demonstrating occlusion. There was minimal placental damage at the laser impact sites, and no fetal abnormalities were detected. Long-term occlusion of placental vasculature can be accomplished by fetoscopically delivered laser energy. PMID- 2916638 TI - Effects of outflow pressure on fetal lymph flow. AB - The purpose of this study was to determine to what extent fetal thoracic duct lymph flow may be reduced by increases in fetal venous pressure. In pregnant sheep the fetal left thoracic lymph duct was catheterized at the base of the neck and this catheter was connected to a jugular-vein catheter so the lymph could spontaneously return to the fetal circulation. At 5 days after catheter implantation in nine unanesthetized fetuses at 133 +/- 1 (SE) days' gestation, lymph flow was measured by disconnecting the lymphatic catheter from that in the jugular vein and varying outflow pressure of the lymphatic catheter independent of venous pressure. Whenever outflow pressure was negative, lymph flow was independent of outflow pressure and averaged 0.66 +/- 0.05 ml/min. When outflow pressure of the left thoracic duct was increased above zero, lymph flow decreased linearly with outflow pressure and flow stopped at an outflow pressure of 11.5 +/ 0.6 mm Hg. At a normal venous pressure of 3 mm Hg, the lymph-flow sensitivity to venous pressure was such that a 1 mm Hg rise in venous pressure reduced lymph flow by 12.7% +/- 1.2%. Thus it appears that fetal lymph flow is very sensitive to outflow pressure and only moderate elevations in venous pressure potentially may lead to fetal edema. PMID- 2916639 TI - Resistance of the rat embryo to elevated maternal epinephrine concentrations. AB - This study examined the effects of a chronic maternal infusion of epinephrine on development of the rat embryo. Epinephrine was infused during days 1 to 8, 8 to 15, or 15 to 22 of pregnancy to cover periods of implantation, embryogenesis, and rapid fetal growth, respectively. Infusions were accomplished with osmotic minipumps to avoid repeated handling stress. The infusion rate of 0.125 micrograms/min elevated resting plasma concentrations of epinephrine in nonpregnant rats by about sevenfold (from 0.28 to 1.98 ng/ml). Under these conditions, epinephrine did not affect the number of rats maintaining pregnancy, their litter size, or the numbers of resorptions, fetal deaths, and malformations. Fetal and placental weights were unaffected except for a slight trend for fetal weight to be depressed in larger litters of rats treated during days 15 to 22. It seems that the rat embryo is resistant to elevations of epinephrine concentrations equivalent to those observed under mild to severe stress conditions. PMID- 2916640 TI - The effect of pretreatment with magnesium sulfate on the initiation of seizure foci in anesthetized cats. AB - The therapeutic effect of magnesium sulfate remains unknown. Its role as an anticonvulsant is controversial. The effect of pretreatment with parenteral magnesium sulfate on the ability to initiate penicillin-induced seizure foci in anesthetized cats was studied. All animals in the experimental group achieved serum magnesium levels of greater than 10 mg/dl. No significant difference in epileptic spike frequency between the experimental and control groups was demonstrated. PMID- 2916642 TI - Scalp platelet counts and management of immunologic thrombocytopenic purpura. PMID- 2916641 TI - Ontogeny of CA 125 antigen in pregnancy: immunoradiometric determination in amniotic fluid and immunohistochemical localization in fetal membranes. AB - CA 125 antigen was measured in amniotic fluid, maternal blood, cord blood, and fetal urine by a commercially available immunoradiometric assay kit. The amniotic fluid was obtained from 99 normal pregnancies at various gestational ages. The mean antigen levels were 29,676, 3350, and 1680 U/ml in amniotic fluid of the first, second, and third trimesters, respectively. In maternal blood, 12.5% of pregnant women in the first trimester of pregnancy showed elevated levels of CA 125 (65 to 100 U/ml). Late in gestation, CA 125 levels in cord blood and fetal urine were always less than 65 U/ml. Immunohistochemical study of CA 125 in fetal membranes, placenta, and decidua showed the presence of antigen only in the amnion. These results suggest that CA 125 is shed into amniotic fluid directly from the amniotic membrane. PMID- 2916643 TI - The moon and menses. PMID- 2916644 TI - Ovarian cysts and oral contraceptives. PMID- 2916645 TI - Immunohistochemical localization of blood-retinal barrier breakdown in human diabetics. AB - Localization of the site of blood-retinal barrier breakdown in diabetes has been controversial. It has been particularly difficult to make assessments in clinical material where the use of tracer materials may not be practical. In this study, immunohistochemical staining for albumin was performed on paraffin-embedded eyes from patients with no known ocular disease and those with various stages of diabetic retinopathy. No extravascular albumin was detected in the retina or retinal pigment epithelium (RPE) of normal nondiabetics or diabetics with no ocular findings, but it was detected in 12.5% of mildly affected diabetics, 20% of background diabetic retinopathy cases, and 89% of proliferative diabetic retinopathy cases. The inner retinal vasculature appeared to be the primary site of leakage in diabetics because all cases demonstrating extravascular albumin positivity expressed it in the inner retina. It usually permeated the vessel walls and spread along the inner surface of the retina. Some of these cases also contained albumin in the outer retina and RPE, suggesting that additional leakage also may occur through the RPE. A case of cytomegalovirus (CMV) retinitis showed albumin staining predominantly in the inner retina, whereas a rhegmatogenous retinal detachment showed only outer retina staining. These data suggest immunohistochemical staining for albumin may be a useful technique for localizing blood-retinal barrier breakdown. PMID- 2916647 TI - Histogenesis of stromal cells in cerebellar hemangioblastomas. An immunohistochemical study. AB - Fifteen cerebellar hemangioblastomas were examined by immunohistochemistry for expression of neuron-specific enolase (NSE) and various neuropeptides using the avidin-biotin-complex peroxidase reaction with the following antibodies: NSE, synaptophysin, serotonin, substance P, vasoactive intestinal peptide (VIP), neuropeptide YY, neurotensin, and leu-enkephalin. In all tumor biopsies most of the stromal cells were positive for NSE. About 30% of the stromal cells showed a weak cytoplasmic synaptophysin positivity. Approximately 25% of the stromal cells were labeled with antibodies against substance P and neuropeptide YY. The partly strong reactivity was localized preferentially in perinuclear regions. These positive cells were mainly distributed in small cell clusters but were also scattered in the tumor parenchyma. In all tumor biopsies scattered cells exhibited strong perinuclear enkephalin positivity, corresponding probably to mast cells, whereas stromal cells were entirely negative. For serotonin, VIP, and neurotensin no specific reaction was seen. On the basis of these findings it is proposed that hemangioblastomas have a neuroendocrine component. PMID- 2916646 TI - The lesions of an ovine lysosomal storage disease. Initial characterization. AB - An inherited disease associated with deficiencies of beta-galactosidase and alpha neuraminidase has been identified recently in sheep. The clinical signs, the deficiency of lysosomal enzymes, and the familial nature of the disorder suggested that the condition was a lysosomal storage disease. Four affected sheep were necropsied and their tissues were examined by histopathologic and histochemical methods to determine if the lesions were consistent with a lysosomal storage disease. Central nervous system neurons were enlarged with finely to coarsely granular cytoplasmic material, or less often, neurons were distended with multiple, variably-sized vacuoles. Loss of neurons without gliosis was evident and the Nissl substance was either dispersed and fragmented or condensed around the nuclei of remaining neurons. Neurons of intestinal and other peripheral ganglia, retinal ganglion cells, and heart Purkinje fibers were enlarged similarly. White matter of the cerebrum and spinal cord had numerous spheroid to ellipsoid axonal enlargements. Periportal hepatocytes and renal epithelial cells were enlarged with marked vacuolation. The neuronal storage material stained intensely with periodic acid-Schiff/alcian blue, with Luxol fast blue, for acid phosphatase, and moderately with oil red O stains. Renal and hepatocyte storage material stained intensely with oil red O and moderately with periodic acid-Schiff/alcian blue and Sudan black B stains. The lesions in these sheep were consistent with those of a lysosomal storage disease. Both neuronal and visceral storage occurred, but the neuronal storage was more severe. PMID- 2916648 TI - Identification of a 185 kd Maclura pomifera agglutinin binding glycoprotein as a candidate for a differentiation marker for alveolar type II cells in adult rat lung. AB - In adult rat lung the lectin Maclura pomifera agglutinin (MPA) binds apically to alveolar type II (ATII) cells but not to alveolar type I (ATI) cells. This suggests that the presence of MPA binding glycoproteins might be a criterion by which to distinguish the differentiated state of these two adult alveolar epithelial cells. The authors therefore studied MPA binding glycoproteins of ATII cells, comparing, biochemically and cytochemically, MPA binding glycoproteins in freshly isolated ATII cells with those in cultures of ATII cells that are "dedifferentiating" or have "dedifferentiated" as a result of growth on tissue culture plasticware. A MPA binding glycoprotein (185 kd) that is present in freshly isolated "differentiated" ATII cells and then is subsequently lost as isolated ATII cells "dedifferentiate" in tissue culture has been identified. This 185 kd MPA binding glycoprotein alone, or expressed in conjunction with other proteins, is a candidate for a differentiation marker for ATII cells. Preliminary data suggests that this 185 kd MPA binding glycoprotein is not found in ATI cells. PMID- 2916649 TI - The in vitro interactions between serum lipoproteins and proteoglycans of the neointima of rabbit aorta after a single balloon catheter injury. AB - The effect of injury-induced alterations in the aortic neointimal proteoglycans on their binding with homologous serum lipoproteins was examined. Proteoglycans of the aortic intimal-medial tissues of rabbits that had undergone denudation with a balloon catheter 12 weeks earlier were isolated after homogenization of the tissues in 0.33 M sucrose, ultracentrifugation and subsequently by gel exclusion chromatography. Lipoproteins from the plasma of healthy donors were prepared by sequential, ultracentrifugal floatation after density adjustment with KBr. To study the interactions, aliquots of electrophoretically pure very low density lipoproteins (VLDL, d less than 1.006 g/ml), low-density lipoproteins (LDL, d = 1.019-1.063 g/ml), or high-density lipoproteins (HDL, d = 1.210 g/ml) were incubated with proteoglycans in the presence of Ca++ and Mg++ at 4 C. The amount of cholesterol found in the resulting pellet was measured as a marker of the binding capacity of the proteoglycans. Among lipoprotein fractions both VLDL and LDL showed strong binding with proteoglycans, whereas no appreciable binding was observed when incubation experiments were done with HDL. There were significant differences in the lipoprotein binding capacity of proteoglycan of control and injured animals, indicating that injury induced changes in proteoglycan composition exert profound influences on their ionic interactions. PMID- 2916650 TI - Cell surface molecules of human melanoma. Immunohistochemical analysis of the gp57, GD3, and mel-CSPG antigenic systems. AB - The rapidly expanding list of monoclonal antibodies (MAbs) to human cell surface antigens provides reagents to probe the biology of malignant melanoma and to develop new diagnostic and therapeutic approaches to this disease. The criteria used to select MAb-defined antigens as targets for passive immunotherapy or immunolocalization of melanoma include: 1) consistent antigen expression in melanomas, 2) restricted antigen distribution in normal tissues and nonmelanocytic tumors, and 3) cytotoxic activity of the MAb or MAb conjugates. The present study examined the tissue distribution of three prototype melanoma cell surface antigens, the Mr 57,000 glycoprotein (gp57) recognized by MAb A42, the GD3 ganglioside, and the mel-CSPG chondroitin sulfate proteoglycan. The avidin-biotin immunoperoxidase method was used to examine a large panel of normal tissues and over 150 malignant tumors. It was found that A42 has a highly restricted distribution in normal tissues and is expressed in subsets of melanomas and nonmelanocytic tumors. It was also found that GD3 and mel-CSPG are more widely distributed in normal tissues and among tumors than was thought previously. These immunohistochemical patterns provide an essential data base to evaluate the ongoing clinical trials employing MAbs to GD3 and mel-CSPG for the therapy and immunolocalization of melanomas, and they identify gp57 as a potential marker for subsets of normal and transformed melanocytic cells. PMID- 2916652 TI - The fibrillar nature and structure of isoproterenol-induced myocardial fibrosis in the rat. AB - A study of isoproterenol-induced (1 mg/kg) myocardial fibrosis in the rat was undertaken, taking advantage of the differential colorization provided by thick and thin collagen fibers to picrosirius red and polarization microscopy. The objective was to monitor the sequence (day 1, 2, 3, 4, and 8), fibrillar composition, and nature of isoproterenol-induced collagen remodeling, which was found previously to adversely influence myocardial stiffness. The following were found: 1) a distortion and widening of intermuscular spaces on day 1 that was accompanied by the disruption of collagen fibers; 2) by day 2, these spaces were closing and a new fibrillar collagen network had appeared consisting primarily of thinner collagen fibers that crossed over muscle fibers; 3) the new fibrillar network took on a clear crisscrossing pattern on day 3 and 4 as an ever increasing number of thicker fibers became entwined perpendicular to the thinner fibers; and 4) by day 8, a dense mesh of thick and thin collagen fibers had formed to encircle muscle while a greater number of intermuscular spaces, previously devoid of collagen, were now filled with thicker and thinner collagen fibers. Thus, isoproterenol-induced myocardial fibrosis is initiated by the appearance of interstitial edema and fibrillar collagen disruption and is followed soon thereafter by the formation of thinner collagen fibers that extend across muscle fibers and into which thicker collagen fibers become entwined in a crisscrossing pattern. Once formed, this mesh of collagen fibers encircles cardiac muscle. This pattern of fibrous tissue formation may entrap and isolate myocytes so that the mechanical behavior of muscle and the intact myocardium becomes abnormal. PMID- 2916651 TI - A 90-kd surface antigen from a subpopulation of smooth muscle cells from human atherosclerotic lesions. AB - A monoclonal antibody, designated 10F3, that reacts with an antigen with a molecular weight of 90,000 daltons has been obtained after immunization of BALB/c mice with long-term cultured smooth muscle cells (SMC) originally isolated from fetal human aorta (fSMC). In adults the antigen is present on venous, arterial and capillary endothelial cells of heart, kidney, liver, spleen, intestine, skin, uterus, placenta, and arteries only, as shown by immunohistochemical investigation using the PAP technique. The antigen 10F3 is also present on the mesenchymal cells of human fetal tissues (7 and 18-week-old fetuses) and on SMC of 7-week-old fetal aorta, and a subpopulation of cells reacting with 10F3 antibody also has been found in atherosclerotic intima. Double staining using 10F3 antibody and muscle actin-specific monoclonal antibody HHF-35 showed that the antigen-positive cells are smooth muscle cells. In primary culture of adult SMC, antigen-positive cells were detected 2 days after seeding (about 90% positive in medial and intimal cultures). It is suggested that 10F3 is a mesenchymal antigen that, lost during differentiation by cells other than endothelium, but expressed again by the SMC involved in atherogenesis. PMID- 2916653 TI - Tumor necrosis factor induces glomerular damage in the rabbit. AB - Tumor necrosis factor (TNF) is a polypeptide hormone produced by activated macrophages detectable in the circulation of experimental animals given endotoxin. Recent evidence strongly suggests that many of the deleterious effects of endotoxin in experimental animals are mediated by TNF. Because endotoxemia in experimental animals and humans is associated with glomerular damage the present investigation was designed to establish whether TNF directly induces glomerular functional and structural changes. Twenty-three rabbits were given human recombinant TNF at the doses of 0.08, 0.8, and 8.0 micrograms/kg/h as a continuous 5-hour intravenous infusion. Animals were killed at the end of the infusion. All rabbits given 0.8 and 8.0 micrograms/kg/h TNF developed anemia (Ht value decrease at 5 hours: 0.8 microgram/kg/h, 15%; 8.0 micrograms/kg/h, 16%); leukopenia (leukocyte count decrease at 5 hours: 0.8 micrograms/kg/h, 47%; 8.0 micrograms/kg/h, 59%); thrombocytopenia (platelet count decrease at 5 hours; 0.8 micrograms/kg/h, 45%; 8.0 micrograms/kg/h, 57%). Rabbits given 8.0 micrograms/kg/h also had renal failure (serum creatinine from 1.02 +/- 0.15 to 1.64 +/- 0.34 mg/dl). By light microscopy only occasional polymorphonuclear leukocytes in the glomerular capillaries were detectable in rabbits infused with 0.08 micrograms/kg/h TNF, whereas with 0.8 micrograms/kg/h TNF the presence of inflammatory cells in the glomerular capillaries was the prominent finding. With 8.0 micrograms/kg/h TNF beside leukocyte accumulation, fibrin was detected in the glomerular capillary lumens of two of eight animals. Electron microscopy found dose-dependent glomerular endothelial cell damage in animals given TNF with fibrinlike material in the capillary lumens. Glomerular changes induced by TNF were remarkably similar to those previously found in animals given endotoxin. Thus, TNF is likely to be the mediator of endotoxin-induced glomerular damage and can be regarded as a new mediator of macrophage-dependent damage in glomerulonephritis. PMID- 2916654 TI - Neonatal hemochromatosis. The regulation of transferrin-receptor and ferritin synthesis by iron in cultured fibroblastic-line cells. AB - The authors have investigated the hypothesis that neonatal hemochromatosis (NH), a generally fatal disease of infancy, is due to abnormalities in cellular response to ambient levels of iron. The clinical and necropsy findings in two infants with NH, the results of evaluations for iron-storage disease in their first-degree relatives, and the results of the authors' studies of ferritin and transferrin-receptor (TfR) synthesis in NH and normal fibroblasts are presented. No differences between cultured skin fibroblasts from a normal infant and similar cells from the two infants with NH were seen with respect to TfR and ferritin synthesis rates or their modulation by iron. NH and adult idiopathic hemochromatosis (AH) share a pattern of siderosis in which epithelial and mesenchymal elements contain large quantities of stainable iron, while reticuloendothelial elements contain almost none. Although no familial correlation between NH and AH has been established, and none appeared to exist in these two families, the authors' results parallel those of previous studies of various cell types from persons with AH. The abnormalities in cellular iron handling, undefined at present, that are associated with the phenotype common to NH and AH do not appear primarily to involve the regulation by iron of rates of TfR and ferritin synthesis. PMID- 2916656 TI - Program of the fifty-eighth annual meeting of the American Association of Physical Anthropologists. San Diego, California, April 4-8, 1989. Abstracts. PMID- 2916655 TI - Cytoarchitectural analysis of epithelial sheets formed in vitro by hepatic tumor cells possessing defined intermediate-sized filament cytoskeletal abnormalities. AB - Established 72/22 rat hepatic tumor cells, which bear well-characterized cytoplasmic abnormalities of intermediate filament (IF) network organization, form monolayer "sheets" of tightly juxtaposed epithelial cells at high culture population densities. The distribution of desmosomal complexes and their affiliated tonofilaments, as well as the regulation of cytokeratin/vimentin IF and actin microfilament contents were assessed during construction of this in vitro "epithelium." 72/22 cells formed desmosomal junctions throughout the length of the cellular perimeter. Compared with low population density cultures, fully confluent sheets of 72/22 cells exhibited a down-regulated cytoskeletal actin content and increased level of cytokeratin synthesis. Despite gross IF cytoarchitectural abnormalities, 72/22 cells normally modulated the content of specific structural elements within both the IF and microfilament networks in response to increasing cell-cell contact. Furthermore, these data support the concept that neither the structural integrity nor the topographic distribution of the desmosome array are dependent on tonofilament anchorage or IF scaffold organization. PMID- 2916657 TI - Dietary protein restriction and renal injury in the spontaneously hypertensive rat. AB - We examined the influence of a low-protein diet on the course of the renal injury in spontaneously hypertensive rats (SHR) and SHR given antihypertensive drug therapy (SHRD). Antihypertensive drug treatment was hydralazine, reserpine, and chlorothiazide. Wistar-Kyoto (WKY) rats served as normotensive controls. SHR, SHRD, and WKY were each placed on a 24, 14, and 10% protein diet at 5 wk and followed to 80-90 wk of age. Untreated SHR showed a steady rise in protein excretion from 5 to 70 wk regardless of dietary protein content. Protein excretion in SHRD on a 24% protein diet was similar to untreated SHR. However, SHRD on a 14 or 10% diet had a more moderate increase in protein excretion. Glomerular, tubular, and vascular pathology in untreated SHR was not influenced by dietary protein intake. Despite successful antihypertensive therapy, kidney pathology in SHRD on a 24% diet was not significantly different from untreated SHR. In contrast, SHRD on 14 or 10% protein diets had less segmental glomerulosclerosis and vascular pathology than untreated SHR. The results indicate that dietary protein restriction does not influence the course of renal injury in untreated SHR. However, the combination of antihypertensive drug therapy with protein restriction in SHR delays and may arrest progression of glomerulosclerosis and proteinuria. PMID- 2916658 TI - K+ channel currents in basolateral membrane of distal convoluted tubule of rabbit kidney. AB - To examine the nature of ion-conductive pathways in the basolateral membrane of rabbit distal convoluted tubule (DCT), we recorded single-channel currents from the tubule segment isolated from collagenase-treated kidney. Using cell-attached patch pipettes filled with 130 mM KCl, 5.4 mM CaCl2, and 10 mM N-2 hydroxyethylpiperazine-N'-2-ethanesulfonic acid (pH 7.4), we observed K+ channels in the basolateral membrane of DCT, having two different single-channel conductances of 48.7 +/- 1.4 (n = 9) and 60.6 +/- 1.4 pS (n = 7). Both types of channels were completely blocked by 0.1 mM BaCl2. Both channels have same open probability of approximately 0.5 at the intrinsic basolateral membrane voltage and were recorded with similar incidence. Mean open and closed times were 31.5 +/ 5.2 and 41.3 +/- 16.0 ms for the smaller channel, and 31.5 +/- 5.1 and 36.7 +/- 8.7 ms for the larger channel, respectively. These kinetic properties did not show any clear voltage dependence in both channels. Because of apparent similarity of channel kinetics, it is possible that both activities might represent different states of the same channel. For definite conclusion, however, further investigations are necessary. In three recordings from 54 successful patches, we observed a flickering channel with rapid kinetics, which was insensitive to 1 meq/l Ba2+. The conductance of this channel was 76.6 pS (n = 2). The extrapolated zero current voltage was 76.0 mV (n = 2), indicating that this channel is permeable to K+. From these results, we suggest that K+ channels constitute conductive pathways for K+ in the basolateral membrane of rabbit DCT. PMID- 2916659 TI - In vivo indicator dilution kinetics of PAH transport in dog kidney. AB - In vivo multiple indicator-dilution (MID) data were analyzed using a computer assisted mathematical model of transepithelial cell transport to determine p aminohippuric acid (PAH) transport kinetics across the proximal tubular antiluminal (ALM) and luminal (LM) membranes. A bolus of 125I-labeled albumin (plasma reference), [14C]creatinine (interstitial reference), and tracer [3H]PAH was injected into the left renal artery of anesthetized mongrel dogs (n = 21), and immediate serial sampling of the left renal venous and left and right urine outputs was performed (control). MID runs were then repeated in the same dog following intravenous infusion of unlabeled PAH. For all plasma PAH concentrations ([PAH]P), the steady-state unidirectional flux coefficients were calculated at the ALM and LM. The computer-derived unidirectional flux coefficients were in keeping with active ALM transport and passive, carrier mediated LM transport. The Km calculated for ALM uptake (interstitium to cell) was 0.51 mM. PAH transport was completely inhibited by probenecid. As [PAH]P increased, the renal vein mean transit time ratio t[3H]PAH/t[14C]creatinine was greater than 1.0, indicating backflux from cells into the interstitium, then declined toward unity, as ALM and LM transport became saturated. This study, which used PAH as a model substrate demonstrated the feasibility of utilizing computer-assisted mathematical models to quantitate the kinetics of transepithelial transport from in vivo experimentation. PMID- 2916660 TI - Renal microvascular effects of vasopressin and vasopressin antagonists. AB - The effects of vasopressin (AVP) and vasopressin antagonists on lumen diameters of cortical afferent and efferent arterioles isolated from rabbit kidneys were examined. Over a concentration range of 10(-14) to 10(-7) M, AVP had no effect on lumen diameters of afferent arterioles, although the arterioles were responsive to norepinephrine. Similarly, addition of 10(-8) M AVP to the lumen of afferent arterioles or to the bath of arterioles pretreated with indomethacin had no effect. In contrast, AVP caused a concentration-dependent reduction of lumen diameters of efferent arterioles. AVP was approximately 100-fold more potent than norepinephrine in producing contraction of efferent arterioles. The V1-selective antagonist, [d(CH2)5Tyr(Me)]AVP, and the V1/V2-antagonist, d(CH2)5D-Tyr(Et) desGlyVAVP, inhibited the vasoconstriction produced by AVP in a concentration dependent but noncompetitive manner. The V2-selective antagonist, [d(CH2)5D Ile]VAVP, had no significant effect on AVP-induced vasoconstriction. We conclude that, under the in vitro conditions used, AVP selectively contracts efferent arterioles. The results provide direct evidence for a postglomerular vascular effect of AVP in the renal cortex. This activity, together with its previously described effects on the glomerulus, suggests that AVP may produce changes in glomerular function and/or peritubular forces that are involved in tubular reabsorption. PMID- 2916662 TI - Potassium secretion by the cortical collecting tubule: effect of C1 gradients and ouabain. AB - In various epithelia K and Cl transport are molecularly coupled and KCl cotransport is dependent on the Na-K pump. The present study examines 1) the effect of a bath-to-lumen Cl gradient on K secretion during active Na transport and 2) the effect of basolateral ouabain on K secretion and Na absorption in the presence and the absence of a bath-to-lumen Cl gradient. Under symmetrical conditions there was significant K secretion (JK = -24.0 +/- 3.9 pmol.mm-1.min-1) and Cl secretion (JCl = -15.7 +/- 3.7 pmol.mm-1.min-1). Transepithelial voltage (VT) was significantly lumen negative (-25.3 +/- 5.9 mV), and Cl secretion occurred against its electrochemical gradient by a transcellular mechanism. Increasing bath [Cl] did not hyperpolarize VT; in fact there was a tendency for VT to depolarize and K secretion was not stimulated. However, ouabain significantly inhibited active Cl secretion and net Na absorption both in the presence and absence of a bath-to-lumen Cl gradient. Furthermore, ouabain totally inhibited K secretion in the absence of external ion gradients but inhibited K secretion by only 50% in the presence of a bath-to-lumen Cl gradient. This ouabain-insensitive K secretion exhibited a codependence on Cl secretion. Thus K secretion may occur passively, utilizing Cl movement down its electrochemical gradient when active Na transport is inhibited by ouabain. The results are compatible with the presence of a Cl-linked K-secretory process in the rabbit CCT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2916661 TI - Brush-border TEA transport in intact proximal tubules and isolated membrane vesicles. AB - The efflux of the organic cation, tetraethylammonium (TEA), across proximal cell luminal membranes was studied using intact, perfused rabbit proximal tubules and isolated rabbit cortical brush-border membrane vesicles (BBMV). Increases of either the extravesicular H+ concentration (from pH 7.5 to pH 6.5) or the extravesicular concentration of unlabeled TEA (from 0.1 to 0.5 mM) increased the rate of efflux of radioactively labeled TEA from BBMV. Similarly, when proximal tubules were preloaded with labeled TEA and then submerged in a mineral oil bath, a rapid increase in either the H+ concentration (from pH 7.5 to pH 5.8) or the TEA concentration (from 0 to 1 mM) of the tubular perfusate produced an acute increase in efflux of the labeled TEA across the luminal brush-border membrane. These results with intact tubules and isolated membranes are consistent with previous suggestions that TEA transport across the brush border of proximal tubule cells involves a carrier-mediated countertransport process and represent the first demonstration with intact proximal tubules that the secretory flux of TEA occurs by an exchange with H+. PMID- 2916663 TI - Impaired preservation of GFR during hypotension in preexistent renal hypoperfusion. AB - Autoregulation of renal blood flow and filtration rate was studied using micropuncture technique in Munich-Wistar rats with acute water deprivation (AWD) or congestive heart failure (CHF). In the first set of experiments, reduction of renal perfusion pressure to approximately to 70% of its initial value resulted in uncoupling of glomerular plasma flow rate and single-nephron glomerular filtration rate (GFR) (i.e., disproportionally profound fall in the latter) in AWD and CHF rats, whereas both indices changed little in normal control (NC) rats. The profound decrease in single-nephron GFR in AWD and CHF rats was primarily due to a reduction in glomerular capillary pressure (change from base line value was -29 +/- 2% in AWD, -27 +/- 1% in CHF, and -8 +/- 2% in NC). This profound fall in glomerular capillary pressure in AWD and CHF rats was associated with a reduction in efferent arteriolar resistance, which contrastingly increased in NC. To investigate the mechanism underlying this unique efferent arteriolar responsiveness in AWD and CHF, the response of renal arterioles to exogenous angiotensin II was examined in separate groups of AWD, CHF, and NC. There was a markedly attenuated efferent arteriolar vasoconstrictive response in AWD and CHF (the change of efferent arteriolar resistance in both groups was some 5% of that in NC). Thus impairment in the ability to preserve GFR in these two conditions is attributed, at least in part, to altered efferent arteriolar response in the face of reduced renal perfusion pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2916664 TI - Effect of acute metabolic acidosis on ammonia metabolism in kidney. AB - To understand the mechanisms that initiate the increase in ammonia formation during acute acidosis in kidney [amino-15N]- and [amino-15N]glutamine were used as substrates in isolated perfused rat kidney experiments. Perfused kidneys from methionine sulfoximine-treated rats take up glutamine nitrogen at the rate of 1.50 +/- 0.08 mumol.g kidney-1.min-1 while forming ammonia at a rate of 0.65 +/- 0.09 mumol.g.kidney-1.min-1. Mass spectrometer analysis of the perfusate and urine reveals that ammonia is formed from the amide nitrogen of glutamine at the rate of 0.32 +/- 0.06 mumol.g kidney-1.min-1 and ammonia is formed from glutamate derived from glutamine at the rate of 0.21 +/- 0.04 mumol.g kidney-1.min-1. The balance of the ammonia formed is from unidentified endogenous sources. Addition of HCl to the perfusate to lower perfusate pH increases ammonia formation to 1.09 +/- 0.10 mumol.g kidney-1.min-1. The results exclude a role for the purine nucleotide cycle during acute acidosis and confirm that ammonia formation from glutamate derived from glutamine is via glutamate dehydrogenase. Lowering perfusate pH increases the rate of glutamine deamidation significantly by 0.33 +/ 0.06 mumol.g kidney-1.min-1 and increases the rate of ammonia formation via glutamate dehydrogenase insignificantly by only 0.08 +/- 0.04 mumol.g kidney 1.min-1, whereas ammonia formation from endogenous sources remains unchanged. The results demonstrate that regulation of glutamine deamidation is an important controlling step in ammonia formation during acute metabolic acidosis in kidney. PMID- 2916665 TI - Reversible downregulation of thiazide diuretic receptors by acute renal ischemia. AB - Receptors for thiazide diuretic drugs in the rat renal cortex have recently been identified through the binding of [3H]metolazone, a potent diuretic with a thiazide-like mechanism of action. The present studies describe the rapid and reversible alterations that occur in thiazide receptors following acute renal ischemia in the rat. The apparent density of thiazide receptors in kidney membranes as measured by the binding of [3H]metolazone was reduced by 90% following 10 min of renal ischemia produced by clamping the renal pedicle. With release of the clamp and subsequent reperfusion for 10 min, thiazide receptor density returned to within 40% of control levels. Ischemia did not alter apparent affinity of receptors for [3H]-metolazone. Sections prepared from renal cortex and incubated in oxygenated media in vitro displayed similar rapid changes in thiazide receptors. Hypoxia of 10- to 30-min duration produced by incubating sections in vitro in nitrogen-saturated media caused a significant decrease in [3H]metolazone binding that was reversible with return to oxygenated media. Similar decreases were obtained in oxygenated sections that were incubated with mitochondrial inhibitors, dinitrophenol and rotenone, but not in sections incubated with ouabain. These results indicate that renal thiazide receptors undergo a rapid and reversible form of regulation and that controlling mechanisms are dependent on metabolic energy. PMID- 2916666 TI - Depolarization-induced alkalinization in proximal tubules. I. Characteristics and dependence on Na+. AB - We used intracellular pH-sensitive and voltage microelectrodes to examine the effects of depolarization on intracellular pH (pHi) in isolated perfused proximal tubules from the tiger salamander Ambystoma tigrinum. Tubules were depolarized by raising [K+] in the bath (b) or lumen (l), or by adding Ba2+ (1 mM) to the bath or lumen, always in nominally HCO3-free solutions. Increasing [K+]b from 2.5 to 50 mM caused the basolateral membrane to depolarize by an average of 45 mV, and pHi to increase by 0.23 over 3 min. Similar alkalinization was observed when basolateral Ba2+ (1 mM) was used to depolarize the cell at constant extracellular [K+], suggesting that the alkalinization observed during exposure to elevated [K+]b results from depolarization rather than an increase in [K+]b. The initial rate of depolarization-induced alkalinization (DIA) was proportional to the magnitude of the depolarization, regardless of whether tubules were depolarized by elevated [K+]b, elevated [K+]l, or by basolateral Ba2+. An exception was the initial rate of the alkalinization caused by 1 mM luminal Ba2+, which was more than 10-fold greater than that predicted from the depolarization. The voltage and pHi responses to basolateral Ba2+ were smaller in some tubules than others, as were the responses to elevated [K+]l. Tubules with small responses to 1 mM [Ba2+]b had large responses to 50 mM [K+]l, whereas tubules with large responses to 1 mM [Ba2+]b had small responses to 50 mM [K+]l. This variability can be accounted for by differences in the luminal K+ conductance. The DIA was partially inhibited by removal of Na+ from only the lumen or only the bath, but completely inhibited by bilateral Na+ removal. We conclude that the depolarization-induced alkalinization results from additive effects of Na+-dependent processes at both the luminal and basolateral membranes. PMID- 2916667 TI - Depolarization-induced alkalinization in proximal tubules. II. Effects of lactate and SITS. AB - Intracellular pH and voltage microelectrodes were used to further characterize the depolarization-induced alkalinization (DIA) observed in isolated perfused proximal tubules of the tiger salamander Ambystoma tigrinum. Tubules were depolarized by raising basolateral [K+] from 2.5 to 50 mM. The solutions were air equilibrated and nominally HCO3- free (estimated [HCO3-] = 0.2 mM). In the preceding study we showed that the DIA is partially blocked by removal of Na+ from only the lumen or only the bath, but completely blocked by bilateral Na+ removal. In the present study we found that bilateral amiloride (1 mM) had no effect on the DIA, suggesting that Na-H exchange is not involved. In contrast, basolateral 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS) (0.5 mM) partially blocked the DIA, presumably due to inhibition of one or more of three SITS-sensitive basolateral transporters present in amphibian proximal tubules: electrogenic Na-HCO3 cotransport, Na-dependent Cl-HCO3 exchange, and H lactate cotransport. Bilateral removal of all organic substrates, or of only lactate (Lac-) also blocked the DIA partially. As shown elsewhere (A. W. Siebens, and W. F. Boron, J. Gen. Physiol. 90: 799-831, 1987), in the absence of depolarization, luminal Lac- causes a pHi increase due to luminal Lac- entry via a Na-Lac cotransporter, followed by basolateral Lac- exit via an H-Lac cotransporter sensitive to alpha-cyano-4-hydroxycinnamate (CHC). Three lines of evidence indicate that this Na-Lac/H-Lac mechanism is involved in the DIA. 1) As noted previously, the DIA is partially blocked by luminal Na+ removal. 2) With the DIA partially blocked by basolateral SITS, removal of Lac- from only the lumen blocks the remainder of the DIA. 3) Basolateral CHC partially blocks the DIA. Our data suggest that the DIA is mediated by at least two additive mechanisms, a basolateral transporter that is SITS sensitive and Na+ dependent, and the Na-Lac/H-Lac transport system. PMID- 2916668 TI - Downregulation and desensitization of A1-adenosine receptors in embryonic chicken heart. AB - Downregulation of cardiac A1-adenosine receptors and desensitization of the negative inotropic response to adenosine were examined 44 h after pretreatment of 15-day-old chick embryos with phenylisopropyladenosine (R-PIA) or vehicle. The number of A1-adenosine receptors, assessed by 125I-aminobenzyladenosine (125I ABA) binding to crude cardiac membranes, was decreased by 63% (P less than 0.001) after pretreatment of embryos with 1 mumol of R-PIA, from 16.7 +/- 2.4 to 6.2 +/- 1.4 (SD) fmol/mg protein (n = 6). The KD of 125I-ABA binding to the remaining receptors did not differ significantly from control (0.71 +/- 0.45 vs. 0.79 +/- 0.57 nM). A maximally effective concentration of R-PIA (10(-5) M) decreased the developed tension of electrically paced right ventricular (RV) muscle strips from control embryos by 76 +/- 6% (mean +/- SD, n = 7) from its forskolin-stimulated plateau level, whereas the developed tension of strips from R-PIA-pretreated embryos was decreased significantly less, by 38 +/- 4% (P less than 0.001). The potency of R-PIA and the efficacy and potency of carbachol to decrease contractile tension were not changed. The data suggest that chronic exposure of the heart to R-PIA can produce downregulation of A1-adenosine receptors and homologous desensitization of the negative inotropic response to adenosine. PMID- 2916669 TI - Influence of neutrophil depletion on myocardial function and flow after reversible ischemia. AB - We explored the role of polymorphonuclear leukocytes (PMN) in the genesis of contractile dysfunction (myocardial "stunning") and of vascular abnormalities after reversible ischemia. Open-chest dogs underwent a 15-min coronary occlusion and 4 h of reperfusion (REP); treated animals (n = 16) received intravenous goat antiserum against canine PMN, whereas controls received nonimmune goat serum (n = 10) or saline (n = 15). In treated dogs, the average blood PMN levels were 10% of those in saline controls. During ischemia, collateral flow tended to be higher, and paradoxical systolic wall thinning tended to be less in neutropenic dogs, but despite this, recovery of wall thickening after REP was not enhanced in these animals. Similarly, arrhythmias during ischemia or REP did not differ among the three groups. Four hours after REP, both resting and minimal coronary resistance (the latter assessed by adenosine infusion) were higher in the stunned compared with the nonischemic myocardium; these vascular derangements, however, were similar in all three groups. Thus profound neutropenia failed to attenuate mechanical dysfunction, to reduce arrhythmias, and to prevent vascular abnormalities after a 15-min coronary occlusion. Although previous studies have suggested that neutrophils mediate cell death during prolonged ischemia, the present findings suggest that PMN do not contribute importantly to the damage associated with brief, reversible ischemia. The duration of flow reduction may be a critical factor determining whether PMN exacerbate ischemic injury. PMID- 2916670 TI - Contractile function of heterogeneously perfused myocardium in conscious dogs. AB - The contractile function of heterogeneously perfused segments (HET) after circumflex coronary artery occlusion (CAO) was examined in conscious dogs. At 1 h after CAO, regional shortening (SH) in nonischemic segments did not change from pre-CAO base line, and regional endocardial blood flow (REBF) increased (P less than 0.05) to 1.52 +/- 0.20 from 1.06 +/- 0.08 ml.min-1.g of tissue-1. In ischemic segments, SH was replaced by paradoxical bulging, and REBF averaged 0.07 +/- 0.02 ml.min-1.g of tissue-1. In HET with one crystal of each pair in nonischemic myocardium and the other in severely ischemic myocardium, SH at 1 h after CAO was reduced (P less than 0.01) by 53.2 +/- 3.4%. REBF maps constructed with serial sections of ventricular rings containing the crystals revealed that in HET 50 +/- 5% of the myocardium was ischemic. Therefore, in the acute phase of ischemia, the reductions in SH in HET were proportional to the amount of ischemic myocardium between recording sites. In HET, SH significantly recovered (P less than 0.01) over 4 wk after CAO but remained depressed by 26.8 +/- 5.1%. In contrast, SH in ischemic segments did not improve after CAO. In HET, the effects of inotropic stimulation and changes in left ventricular afterload on SH (as percent of base line) were similar before and at 1-4 wk after CAO. Thus, in HET, the level of dysfunction is acutely determined by the amount of ischemic myocardium between recording sites. Over 4 wk after CAO, SH improved substantially in these segments, and contractile function was not adversely influenced by an inotropic stimulation or an increase in ventricular afterload. PMID- 2916671 TI - Effects of steps in cardiac output and arterial pressure in awake dogs with AV block. AB - In awake dogs with atrioventricular block, we examined the responses in total peripheral resistance and atrial rate to square-wave changes in mean arterial pressure or cardiac output. We compared the responses 2-3 min after a step change with the responses 19-20 min after a step. With resetting of arterial pressure control, the compensatory responses should decrease as the baroreceptors reset to the prevailing pressure. With step changes in mean arterial pressure or cardiac output, the responses in both peripheral resistance and atrial rate increased from minutes 2-3 to minutes 19-20. The responses in peripheral resistance also increased in animals studied after bilateral vagal block. All of the above changes were significant in the majority of cases. In another experiment, the animals were "conditioned" by 20 min at imposed high or low pressure. When control was returned to the animal after conditioning at high pressure, arterial pressure was not significantly different (P greater than 0.05) from the initial control levels. When control was returned after conditioning at low pressure, arterial pressure was significantly greater (P less than 0.05) than during the initial control period. These results indicate an absence of resetting of the entire arterial pressure control system. PMID- 2916672 TI - Anatomical determinants of O2 flux density at coronary capillaries. AB - Calculations indicate that the PO2 in plasma falls to zero approximately 3 microns from an erythrocyte at O2 consumption (VO2) characteristic of myocardium (Federspiel, W.A., and A. Popel, Microvasc. Res. 32: 164-189, 1986). We measured distances between individual red cells along capillaries in rat hearts rapidly frozen in situ. Cell spacing varied widely even in branches of the same capillary. Plasma gaps between red cells were divided into two populations, those less than 5 microns and those greater than 5 microns. Mean gap lengths were 2.1 and 16.5 microns, respectively. Although the number of long plasma gaps was underestimated, gaps greater than 5 microns accounted for one-third of observed capillary length. Frozen muscles were also viewed in cross section. Because the depth of penetration of light was approximately equal to 3 microns, counts of red cell-containing capillary profiles in cross section depend on cell spacing as well as on number of cell-containing flow paths. Counts varied markedly with arterial O2 partial pressure, indicating that the capillary surface area functional for O2 transport changes in response to stress. The adaptive role of change in O2 flux density (flux per area) is discussed in light of new knowledge of tissue O2 gradients. PMID- 2916673 TI - Effects of tissue geometry on initiation of a cardiac action potential. AB - We used rabbit ventricular papillary muscles and isolated rabbit ventricular muscle cells to compare the effects of a decrease in cardiac excitability. For the papillary muscles, we defined tissue excitability as the inverse of the current required to initiate a propagated action potential from a local stimulus. For the isolated cells, we defined cellular excitability as the inverse of the current required to initiate a membrane action potential. For papillary muscles, lidocaine with elevated extracellular K+ concentration ([K+]o) decreased maximum rate of rise of membrane potential (Vmax), decreased conduction velocity, and strongly decreased tissue excitability. For the isolated cells, lidocaine with elevated [K+]o decreased Vmax but had little effect on cellular excitability. We interpret our results on the differences of effect on tissue excitability vs. cellular excitability as a consequence of the syncytial nature of the papillary muscle. The cell-to-cell electrical connections produce an electrical load on the locally stimulated region. This electrical load makes the tissue excitability dependent on the amount of inward current that the locally excited cells and the surrounding cells can generate. We simulated these phenomena with numerical solutions of action potential initiation in an isopotential cell compared with a two-dimensional disk of excitable tissue. The simulation results recreate the basic experimental observation that the sensitivity of the current threshold to agents that lower inward current is markedly larger for multidimensional current flow from a source compared with an isopotential system. PMID- 2916674 TI - Uneven blunting of chronotropic baroreflexes in obese Zucker rats. AB - We compared reflex chronotropic responses to intravenously infused drugs in three groups of age-matched normotensive female rats, namely, Sprague-Dawley, lean Zucker, and obese Zucker. Initial mean pressures did not differ between rat groups, but heart rates tended to be lower in obese Zucker rats. Baroreflex impairment was already evident, because heart rate responses to infused phenylephrine (reflex bradycardia) or sodium nitroprusside (reflex tachycardia) were consistently weaker in obese Zucker than in other rats. Regardless of rat grouping, subsequent cholinergic blockade with atropine elevated, whereas beta adrenergic blockade with propranolol lowered, basal heart rates without affecting mean pressure. Reflex heart rate responses were all appreciably reduced after either type of autonomic blockade, and although the extent of inhibition varied between rat groups, the residual heart rate responses remaining after blockade were nonetheless always smaller in obese than in lean rats. This difference suggests that efferent sympathetic and parasympathetic mechanisms normally responsible for mediating heart rate reflexes were unevenly blunted in obese Zucker rats. PMID- 2916675 TI - Vagal stimulation decreases rate of left ventricular relaxation. AB - We determined the effects of vagal stimulation on the time constant (tau) of left ventricular isovolumic pressure decay and on the maximum rates of left ventricular pressure change (dP/dt) during contraction and relaxation in anesthetized dogs. In each dog, the atria were paced at a constant rate of 150 beats/min. We recorded left ventricular pressure waveforms in the absence (control) and in the presence of vagal stimulation at frequencies of 1, 2, and 3 Hz. During the control periods and during vagal stimulation at each frequency, we determined tau, the maximal rate of contraction, and the maximal rate of relaxation from left ventricular pressure waveforms recorded at medium (100 mmHg), high (130 mmHg), and low (73 mmHg) afterloads. Vagal stimulation at a frequency of 3 Hz increased tau by 23%. This effect of vagal stimulation on tau was most pronounced at the high afterload. Vagal stimulation at 3 Hz decreased the maximal rate of relaxation by 19%, but it decreased the maximal rate of contraction by only 8%. Thus vagal stimulation significantly decreased the rate of left ventricular relaxation and had a greater depressant effect on ventricular relaxation than on contraction. PMID- 2916676 TI - Effect of sinoaortic denervation on arousal responses to hypotension in newborn lambs. AB - To examine whether hypotension reflexly initiates arousal from sleep and the mechanisms involved, we subjected sleeping lambs to hypotensive stimuli of 1-min duration, before and after sinoaortic denervation (SAD). In intact lambs, hypotension increased the probability of arousal from both quiet sleep (QS) and rapid-eye-movement (REM) sleep. Hypotension resulted in nonarousal in 42% (QS) and 47% (REM) of tests. Arousal time was significantly longer in REM (34.9 +/- 1.8 s, means +/- SE) than in QS (26.0 +/- 1.8 s). Arterial saturation of O2 (SO2) and PO2 measured at the point of arousal were unchanged from control values in those tests in which arousal occurred. In nonarousal tests, there was a significant fall in both SO2 (4.9 +/- 1.2%) and PO2 (21.6 +/- 4.2 mmHg). After SAD, hypotension did not increase the probability of arousal. Nonarousals significantly increased to 75% (QS and REM, P less than 0.02). We conclude that acute hypotension is a potent stimulus for arousal from sleep in newborn lambs. As the arousal response is abolished by SAD and is not correlated with arterial oxygenation, hypotensive arousal appears to be mediated via arterial baroreceptors. PMID- 2916677 TI - Pressure-flow characteristics of coronary collaterals in dogs. AB - In this study we utilized two methods to investigate the pressure-flow, P-F, relationship of the coronary collateral vessels in a beating, blood-perfused, isolated heart preparation. In the first method (free-flow method), 12 dog hearts were perfused at pressures ranging from 100 to 0 mmHg, whereas the retrograde flow (index of collateral flow) was measured on the circumflex coronary artery, LCA, against atmospheric pressure, first during autoregulation and then after maximum vasodilation. In the second method (back-pressure method), the back pressure to retrograde flow was varied from 0 to 100 mmHg, whereas the perfusion pressure to the remaining vessels was maintained constant at 100 mmHg. This procedure was performed on four hearts with and without embolization of the LCA by 25-microns spheres. The free-flow method demonstrated a linear P-F relationship with an average correlation coefficient, r, of 0.98. The pressure intercept was 1.7 +/- 1.2 mmHg. The back-pressure method yielded a relationship that was more curvilinear with an average pressure intercept of 13 mmHg without embolization and 38 mmHg with embolization. An analog of the coronary and collateral circulation was used to illustrate that, in the back-pressure method, changes in the coronary resistance at low pressures contributed to the nonlinearity of the collateral P-F characteristics and that the network formed between the collateral and coronary resistances was responsible for the higher pressure intercept value. PMID- 2916678 TI - Aberrant baroreceptor mechanotransduction in adult Dahl rats on low-salt diet. AB - Single fiber, regularly discharging baroreceptors (n = 118) from adult Dahl salt sensitive (DS) and salt-resistant (DR) rats on a low-salt diet were studied using an in vitro aortic arch-aortic nerve preparation. Pressure thresholds (Pth) and suprathreshold pressure sensitivities (Sth) were determined from responses to slow ramps of pressure. Pressure-diameter relationships measured in each rat were used to transform Pth and Sth values to their mechanical equivalents in terms of aortic wall strain. DS and DR ages were not different (approximately 50 wk). Despite the low-salt diet, DS tail systolic blood pressures were significantly higher than DR by approximately 25 mmHg. Pth averaged 84 mmHg in DR and 97 mmHg in DS. Sth values were similar in DR and DS (average 1.44 and 1.39 spikes.s 1.mmHg-1 in DR and DS, respectively). Increased variance of baroreceptor properties of DS over DR was a prominent finding and necessitated use of nonparametric statistics. The cumulative distribution of Pth values of DS was significantly different from DR, but Sth values were similar. Thus baroreceptor pressure set points are altered in adult DS, but pressure sensitivity per se is not. The differences in pressure parameters were not eliminated by conversion to their mechanical equivalents. Correlation analysis found only weak relationships between Pth and blood pressure for DS and DR (r less than 0.40). Thus in contrast to previous studies in the spontaneously hypertensive rat model, baroreceptors in adult DS on low salt are characterized by elevated variability and a weaker than expected correlation to the prevailing blood pressure in the animal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2916679 TI - Lipoxins A4 and B4 dilate cerebral arterioles of newborn pigs. AB - We determined the effects of lipoxins A4 and B4 on the cerebral microcirculation of neonatal pigs and whether vascular responses were modulated by prostanoids. Pial arteriolar diameters were determined using a closed cranial window and intravital microscopy. Before lipoxin A4 application, arteriolar diameter was 143 +/- 6 microns (means +/- SE). Topical application of lipoxin A4 increased the diameter to 160 +/- 7 microns at 0.1 ng/ml, 167 +/- 7 microns at 1 ng/ml, and 173 +/- 7 microns at 10 ng/ml (n = 9). Before application of lipoxin B4, arteriolar diameter was 146 +/- 7 microns. Topical application of lipoxin B4 increased the diameter to 165 +/- 7, 169 +/- 6, and 175 +/- 6 microns at 0.1, 1, and 10 ng/ml (n = 9), respectively. Intravenous injection of indomethacin (5 mg/kg) or vehicle did not affect these responses. Levels of prostaglandins E2 and F2 alpha in cerebrospinal fluid (measured by radioimmunoassay) did not increase in response to lipoxins. We conclude that lipoxins are dilator stimuli in the cerebral circulation and that prostanoids do not mediate these responses. PMID- 2916680 TI - Optimal hematocrit for canine gastric oxygenation. AB - To determine whether an optimal hematocrit exists at which gastric tissue is maximally oxygenated, chambered segments of resting canine stomach were perfused at a constant pressure while hematocrit was decreased in steps from 60 to 10%. The two groups of animals used were a control group and a second group given pentagastrin to elevate metabolic activity. Total blood flow was inversely related to hematocrit in both the control and pentagastrin-treated animals, and arteriovenous oxygen difference was directly related to hematocrit. Consequently, the relationship between gastric oxygen consumption and hematocrit was parabolic in both groups. Therefore, the oxygen uptake vs. hematocrit data from each experiment were fit to a quadratic equation that was used to calculate the maximal oxygen uptake and the optimal hematocrit for each preparation. Both the maximum oxygen uptake and the optimal hematocrit in the pentagastrin-treated group (2.1 +/- 0.4 ml.min-1.100 g-1 and 45.7 +/- 1.4%, respectively) were significantly greater than in the control group (1.5 +/- 0.4 ml.min-1.100 g-1 and 38.2 +/- 0.7%, respectively). We conclude that an optimal hematocrit exists for the oxygenation of gastric tissue and that it is within the normal hematocrit range under resting conditions. However, the optimal hematocrit is slightly higher than normal during periods of increased metabolic activity. PMID- 2916681 TI - Progressive change in collateral blood flow after coronary occlusion in conscious dogs. AB - This study used a retrospective analysis of infarcted and salvaged tissue samples to determine the patterns of blood flow changes (radioactive microsphere technique) that occur within the area at risk during the first 24 h after coronary artery occlusion (CAO) in conscious dogs. With the triphenyl tetrazolium chloride (TTC) technique, individual samples were selected and included in either the infarcted (TTC-negative) or salvaged (TTC-positive) group. The infarcted and salvaged samples were paired according to blood flow levels of 0.1-0.2, 0.2-0.3, or 0.3-0.4 ml.min-1.g-1 at either 5 min, 1 h, 3 h, or 6 h after CAO. In tissue samples that were salvaged, blood flow rose progressively, i.e., from 5 min to 1 h, from 1 to 3 h, from 3 to 6 h, and from 6 to 24 h. Blood flow to infarcted tissue rose only in the longest interval, from 6 to 24 h after CAO. When blood flow levels were less than 0.1 ml.min-1.g-1, virtually all the samples were infarcted, whereas corresponding lesser amounts of infarction were observed with increasing blood flow levels after CAO. Thus, in the conscious dog, blood flow rises progressively to salvaged but not infarcted tissue within the area at risk. Except for myocardium with blood flow levels less than 0.1 ml.min-1.g-1, the blood flow levels at any of the time points after CAO could not be used to predict necrosis. PMID- 2916682 TI - Mechanics and composition of arterioles in brain stem and cerebrum. AB - The goal of this study was to compare mechanics and composition of arterioles in brain stem and cerebrum. We calculated stress and strain of pial arterioles in anesthetized rats from measurements of pial arteriolar pressure (servo-null), diameter, and cross-sectional area of the vessel wall. Composition of pial arterioles was quantitated using point-counting stereology. Before deactivation of smooth muscle with ethylenediaminetetraacetic acid (EDTA), pial arteriolar pressure and diameter were 28 and 30% greater (P less than 0.05) in brain stem than cerebrum. After EDTA, diameter of arterioles was similar in brain stem and cerebrum. Cross-sectional area of the arteriolar wall was 32% greater (P less than 0.05) in brain stem than cerebrum. Stress-strain curves indicated that distensibility of pial arterioles is greater in brain stem than cerebrum. The proportion of nondistensible (collagen and basement membrane) to distensible (elastin, smooth muscle, and endothelium) components was 20% less (P less than 0.05) in brain stem than cerebral arterioles. We conclude that 1) cross-sectional area of the vessel wall in arterioles of comparable size is greater in brain stem than cerebrum, 2) distensibility of arterioles is greater in brain stem than cerebrum, despite greater cross-sectional area of the arteriolar wall in brain stem, and 3) the proportion of elastic components is greater in brain stem than cerebral arterioles, which may contribute to greater arteriolar distensibility in brain stem. PMID- 2916683 TI - Canine myocardial creatine kinase isoenzyme response to coronary artery occlusion. AB - The response of the myocardial creatine kinase system to acute coronary artery occlusion is not well defined. In the present study, we measured serial changes in myocardial creatine kinase and creatine kinase-MB activities after acute occlusion of the left anterior descending (LAD) coronary artery in 20 open-chest pentobarbital-anesthetized dogs. Tissue samples were obtained from both ischemic and nonischemic left ventricular myocardium at base line and 1-, 3-, and 5-h intervals after LAD occlusion and assayed for total creatine kinase and the isoenzymes creatine kinase-MM, and creatine kinase-MB. Total creatine kinase activity declined significantly in both the ischemic and the nonischemic tissue because of a decline in creatine kinase-MM activity. Concomitantly, creatine kinase-MB activity increased significantly in both the ischemic and the nonischemic tissue. These changes were observed when the duration of the LAD occlusion was 3 h or longer, but not when the duration of the occlusion was 1 h. Thus acute myocardial ischemia causes pronounced changes in the canine myocardial creatine kinase system. These rapid biochemical alterations occur both locally in ischemic tissue and remotely in nonischemic tissue. PMID- 2916685 TI - Mathematical model of dependence of heart rate on tissue concentration of acetylcholine. AB - The change in sinus period elicited by vagal stimulation depends on the rate of acetylcholine (ACh) release from the nerve endings, the rate of ACh degradation in the nodal tissue, and the responsiveness of the sinus node to ACh. Vagal stimulation in anesthetized dogs prolonged sinus period. After cessation of vagal stimulation, the sinus period returned to the prestimulation period. We developed a mathematical model to analyze the dynamics of ACh degradation in the neuroeffector junction and the dependence of sinus period on the concentration of ACh. From the in vitro reaction kinetics of acetylcholinesterase, we derived an analytical expression for the rate of ACh degradation in the intact animal. Our model represents the electrical behavior of the sinus node by the electrical activity of one pacemaker cell with six membrane ionic currents. This model predicts the decline in sinus period of the intact anesthetized dog as acetylcholinesterase degrades ACh in the neuroeffector junction. The half-life of ACh after cessation of vagal stimulation was estimated to be 2.7 s. We conclude that following termination of vagal stimulation, the sinus node of the intact animal responds to ACh as if the sinus node were one oscillator. PMID- 2916684 TI - Erythrocytes reduce liquid filtration in injured dog lungs. AB - In isolated, dog lung lobes with pulmonary vessels filled with different liquids, we measured the rate of weight gain for 5 or 10 min at constant alveolar and vascular pressures under zone 1 conditions (alveolar pressure greater than vascular pressure). We used six different liquids: syngeneic plasma, whole blood (hematocrit = 38 +/- 4%), 4% albumin in Krebs-Ringer solution, washed red blood cells in Krebs-Ringer solution (hematocrit = 37 +/- 6%), and platelet-rich or platelet-poor plasma. We studied the lobes under three conditions: immediate perfusion after removal (less than 30 min), delayed perfusion (2 h or more), or immediate perfusion after removal from air-embolized animals. In lobes that showed low-filtration rate using plasma [less than 0.5 g/(min x 100 g)] substitution of whole blood had no effect on the filtration rate. In lobes that showed high-filtration rates using plasma (delayed perfusion or deliberately injured using air emboli) substitution of whole blood caused a dramatic decrease in the filtration rate, restoring it to the level obtained in uninjured lobes. Platelets had no effect. Thus the red cells specifically reduced abnormally high filtration but did not affect normal filtration. There appear to be three possible mechanisms: 1) red cells physically blocking large leaks; 2) red cells settling on the filtration surface area (osmotic-barrier effect); 3) red cells acting as reducing agents against active oxygen metabolites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2916686 TI - Effect of hemoglobin concentration on critical cardiac output and oxygen transport. AB - We previously found limited tolerance to acute reduction in cardiac output in lambs at the nadir of their physiological anemia [Am. J. Physiol. 253 (Heart Cir. Physiol. 12): H100-H106, 1987]. To determine the effect of hemoglobin concentration [Hb] on critical cardiac output, critical systemic O2 transport, and peripheral O2 extraction, we performed 31 experiments in 12 one-mo-old lambs at four [Hb] (means +/- SD in g/dl): 7.4 +/- 0.6, 10.5 +/- 0.5, 14.5 +/- 0.5, and 16.5 +/- 0.6. Desired [Hb] was obtained by exchange transfusion with packed red cells or plasma. Cardiac output was reduced by inflation of a balloon-tipped catheter in the right atrium, and critical levels were defined at the point where O2 consumption decreased and/or arterial blood lactate concentration increased in response. With lower [Hb], cardiac output was unchanged, systemic O2 transport was reduced, and fractional O2 extraction was increased, keeping O2 consumption constant at base line. As [Hb] was reduced, critical cardiac output was significantly higher, whereas critical systemic O2 transport was independent of [Hb], as were fractional O2 extraction and mixed venous PO2 at the critical point. Thus peripheral O2 extraction was not affected by changes in [Hb] during progressive decreases in cardiac output. We conclude that 4-wk-old lambs have decreased tolerance to reductions in cardiac output and systemic O2 transport because their relative anemia provides them with a base-line cardiac output and systemic O2 transport close to the critical level. PMID- 2916687 TI - Stiffness and shortening changes in myofilament-extracted rat cardiac myocytes. AB - Sarcomere lengths, cell widths, volumes, stiffness, and regional striation uniformity were determined from isolated adult cardiac myocytes. Single cells were examined in the control saline solution followed by a sequence of relaxing, membrane skinning, and myofilament extraction solutions. Cell size and shape parameters were determined from freely dispersed myocytes, whereas stiffness was measured from myocytes attached to a perturbator and tension transducer with micropipettes. There were small changes in cell appearance, size, shape, and stiffness in the relaxing and skinning solutions. However, in 0.17-0.56 M KCl myosin extraction media, cell length declined significantly to 1.19 microns, and stiffness fell to 5-10% of control. The rate of cell shortening and stiffness decline was dependent on KCl concentration and pH. Subsequent exposure to higher ionic strength 0.60 M KI thin filament extraction media elicited additional decreases in stiffness (less than 5% of control) and cell length (0.98 micron). Cell shortening and stiffness decline have similar time courses under the same conditions, and they appear to coincide with A-band disassembly as indicated by electron micrographs. These data suggest that cardiac myocyte stiffness, size, and shape are determined in part by a stressed cytoskeleton that is associated with the myofilament apparatus. PMID- 2916689 TI - Direct diastolic ventricular interaction gain measured with sudden hemodynamic transients. AB - Changes in right ventricular volume affect left ventricular function via direct ventricular interaction mediated by the septum, common myocardial fibers in the free wall, and the pericardium, and also via series interaction mediated by changes in right ventricular output reaching the left ventricle through the pulmonary circulation. To study direct interaction, series interaction must be held constant or removed from the experimental preparation. Because there has been no way to directly measure direct ventricular interaction in the intact circulation, we developed a new method to experimentally separate these two components of ventricular interaction by combining abrupt occlusion of both venae cavae and quick withdrawal of 10-15 ml of blood from the right ventricle. This procedure decreased right ventricular end-diastolic pressure (RVEDP) on the next beat without changing pulmonary venous flow, left ventricular end-diastolic segment lengths, or left ventricular systolic function. The direct interaction gains, quantified as delta LVEDP/delta RVEDP, where LVEDP is left ventricular end diastolic pressure, and delta refers to the change between the beats before and after reducing right ventricular volume, were (means +/- SD) 0.32 +/- 0.32 at steady-state LVEDP = 5 mmHg, 0.38 +/- 0.23 at LVEDP = 10 mmHg, and 0.28 +/- 0.32 at LVEDP = 15 mmHg. These gains were not significantly different (P greater than 0.50). Therefore, we calculated an overall average gain by pooling data from the three base-line LVEDP conditions. This value is 0.33 with 95% confidence interval 0.16-0.51. This 95% confidence interval indicates our data are consistent with many previous reports of diastolic direct interaction. PMID- 2916688 TI - Effects of ATP precursors on ATP and free ADP content and functional recovery of postischemic hearts. AB - It has been proposed that administration of adenine nucleotide precursors might accelerate replenishment of myocardial ATP and "free" ADP, thus improving recovery of depressed contractility of postischemic hearts. To test this hypothesis, Langendorff-perfused rabbit hearts were subjected to 20 min of global ischemia and reperfused for 2 h with normal perfusate (n = 8) or perfusate containing 100 mumol/l of the ATP precursors adenosine (n = 8) or 5-amino-4 imidazolecarboxamide riboside (AICAriboside; n = 8). After reperfusion, developed pressure in untreated hearts averaged 70-80% of base line, whereas ATP content was reduced to approximately 70% of preischemic values. AICAriboside administration did not increase tissue ATP levels or contractility. However, in every heart that received adenosine during reperfusion, ATP content increased from a mean value of 65 +/- 4% of base line to 84 +/- 5% at the end of reperfusion (P less than 0.001). Free ADP also increased in adenosine-treated hearts from 40 to 50% of base line at the beginning of reperfusion, to normal levels by 60 min. However, no improvement in contractility was observed in the hearts that received adenosine. These results support the hypothesis that decreased availability of nucleotide precursors is responsible for depressed ATP levels in postischemic hearts; however, reduced ATP and free ADP levels may not be directly responsible for the depressed function of stunned myocardium. PMID- 2916690 TI - X-ray microanalysis of single cardiac myocytes frozen under voltage-clamp conditions. AB - By means of a patch pipette, an isolated ventricular myocyte was transferred into the taper of a silver holder covered by pioloform film. Once the cell was on the film, the cell was voltage clamped (pulses from -45 to +5 mV at 0.5 Hz). The amount of Ca entry was estimated from the Ca current. When contractility (cell shortening) was potentiated with either five pulses of 0.2 s or four pulses of 1 s, shock freezing was timed 116 or 816 ms after start of the clamp pulse. Electron micrographs from freeze-substituted cells revealed the good preservation of the intracellular compartments. The myocytes were cut at -150 degrees C, and the cryosections were freeze dried. In representative examples, the amount of Ca entry is compared with the subcellular Ca distribution as it is analyzed with energy dispersive X-ray microprobe analysis in cytoplasm, junctional sarcoplasmic reticulum (SR), mitochondria, and the subsarcolemmal space (sarcolemma, peripheral SR, fringe of cytosol). PMID- 2916691 TI - Erythrocytes decrease myocardial hydrogen peroxide levels and reperfusion injury. AB - Reperfusion with untreated, carbon monoxide-treated, or glutaraldehyde-fixed human erythrocytes (RBC) increased ventricular function and decreased myocardial hydrogen peroxide (H2O2) levels [assessed by H2O2-dependent aminotriazole (AMT) inactivation of myocardial catalase activities] of ischemic, isolated rat hearts. In contrast, reperfusion with RBC that lacked catalase (AMT treated) and/or glutathione (N-ethylmaleimide treated) did not increase ventricular function or decrease myocardial H2O2 levels as much as reperfusion with untreated RBC. By comparison, reperfusion with superoxide dismutase-depleted (diethyldithiocarbamate-treated) or anion channel-inhibited (diisothiocyanodisulfonic acid stilbene-treated) RBC increased ventricular function and decreased myocardial H2O2 levels the same as untreated RBC. The results suggest that catalase and/or glutathione in intact RBC can decrease endogenously generated H2O2 and related reperfusion injury in ischemic, isolated perfused hearts. PMID- 2916692 TI - Clearance and urinary excretion of vasopressin in conscious dogs. AB - The purpose of this study was to determine the relationship between plasma arginine vasopressin (PAVP) levels and the urinary clearance rate, the nonurinary plasma clearance rate, and the urinary excretion rate of AVP. Female conscious dogs were given an intravenous infusion of p-aminohippuric acid and inulin, and, after a 90-min control period, the infusion was either continued or AVP was added to the infusate to produce doses of 0, 40, 100, and 200 microU.kg-1.min-1 for the last 90 min of the experiment. The resulting PAVP levels were 1.2, 8.2, 11.4, and 21.6 microU/ml, respectively. The urinary clearance rate of AVP nearly doubled between the infusion rates of 0 and 100 microU.kg-1.min-1. Likewise, the nonurinary plasma clearance rate of AVP also nearly doubled between the infusion rates of 40 and 100 microU.kg-1.min-1. However, at the rate of infusion of 200 microU.kg-1.min-1, both the urinary and nonurinary clearance rates were unchanged compared with the 100-microU.kg-1.min-1 rate. The largest incremental rise in PAVP was observed between the doses of 100 and 200 microU.kg-1.min-1, when the clearance rates were apparently plateaued. The urinary excretion rate of AVP was linearly correlated with PAVP (R = 0.91) under the conditions of this study. The results suggest that the measurement of the urinary excretion rate of AVP is a reliable method of assessing PAVP and that the clearance of AVP increases when PAVP is elevated. PMID- 2916693 TI - Lateral parabrachial lesions attenuate ingestive effects of area postrema lesions. AB - Lesions of the area postrema and adjacent nucleus of the solitary tract (AP lesions) cause rats to consume increased amounts of palatable food in short duration tests. Because the lateral parabrachial nucleus (lPBN) receives a prominent afferent projection from the AP and adjacent nucleus of the solitary tract, it is possible the lPBN plays a role in the altered ingestive behaviors observed in AP-lesioned rats. The present study examines the role of the lPBN in overingestion of highly palatable foods subsequent to AP lesions. We found that lesions of the lPBN alone did not cause rats to consume increased amounts of palatable food. Rather, when lPBN lesions were produced before AP lesions, increased intake of highly palatable food did not occur. Moreover, when AP lesioned rats received subsequent lPBN lesions, the previously established overingestion of palatable foods was abolished. These results indicate that the lPBN is necessary in the pathogenesis of AP lesion-induced overingestion of highly palatable foods. PMID- 2916695 TI - Anesthetic effects on tonic and reflex renal sympathetic nerve activity in awake cats. AB - Renal sympathetic nerve activity (RNA), arterial blood pressure (AP), and heart rate (HR) were simultaneously measured before and after administration of pentobarbital sodium (PB), chloralose (CHL), or urethan (URE) in conscious cats. We examined the time courses and magnitudes of the changes in RNA, AP, and HR over a period of 5 h under anesthesia with spontaneous or artificial respiration. In both respiratory conditions, PB initially decreased and then increased RNA, AP, and HR; CHL sustainedly increased RNA but had almost no effect on AP and HR. Under artificial respiration, URE transiently decreased RNA but had no effect on AP and HR. To examine the baroreflex response of RNA, AP was increased to 150 mmHg by norepinephrine and decreased to 65 mmHg by nitroprusside. RNA responded inversely to the alterations of AP in both awake and anesthetized states. Compared with the awake state, the inverse AP-RNA relationship curve initially shifted downward and then upward under PB, and the slope of the relation curve was initially decreased. On the other hand, under CHL the relationship curve shifted only upward, and the slope increased. Thus the anesthetic drugs affected differently and time dependently tonic and reflex renal sympathetic nerve activity in the conscious cat. PMID- 2916694 TI - Coronary autoregulation and metabolism in hypothermic rat and ground squirrel hearts. AB - An isovolumic Langendorff preparation was used to perfuse rat and ground squirrel (Spermophilus tridecemlineatus) hearts at 37, 27, 17, and 7 degrees C. Perfusion pressure (PP) was randomly increased or decreased (40, 60, 70, 110, 120, or 140 mmHg) from a control PP of 90 mmHg. Coronary flow (CF) was measured immediately after each PP change (initial CF) and after stable flow was observed (final CF). Compared with initial flow, final CF was decreased at high PPs or increased at low PPs (autoregulation) in hearts from both species, but rat hearts did not autoregulate CF or develop left ventricular systolic pressure (LVSP) at 7 degrees C. Squirrel hearts generated LVSP at all temperatures and perfusion pressures. LVSP and initial CF were proportional to PP in both species, but squirrel heart LVSP was independent of PP at 7 degrees C. Myocardial O2 consumption (MVO2) was highly correlated with CF in all hearts at 37 degrees C but not at lower temperatures. Squirrel hearts were more efficient (MVO2 vs. HR X LVSP) than rat hearts at low temperatures but less efficient at 37 degrees C. The intrinsic temperature adaptations displayed by squirrel hearts would support continued myocardial function when body temperature and blood pressure fluctuate throughout the stages of hibernation. PMID- 2916696 TI - Activation by saccharides of a cation-selective pathway on canine lingual epithelium. AB - Responses of isolated canine lingual epithelium in an Ussing chamber to D-glucose and fructose reveal events associated with taste transduction. With the use of isotopic flux studies, together with ion substitution and pharmacological and voltage clamp measurements, it was found that the stimulation of ion transport by D-glucose arises from an increase in the influx of cations through a cation selective pathway. This influx of cations is completely inhibited by 0.1 mM amiloride. The stimulation of transport by fructose in 0.05 M KCl and by D glucose in 0.05 M RbCl was also inhibited by amiloride, demonstrating that the saccharide-stimulated entry pathway was specific for neither hexose sugars nor for Na. Saccharide stimulation of canine lingual epithelia does not appear to be modulated by increases in intracellular levels of adenosine 3',5'-cyclic monophosphate, guanosine 3',5'-cyclic monophosphate, or Ca. The Na that enters taste cells on saccharide stimulation exits them via the ouabain inhibitable Na+ K+-adenosinetriphosphatase located in the serosal membranes. PMID- 2916697 TI - Energy expenditure during stress ulcer formation in vulnerable rats. AB - Rat pups separated early from their mothers at day 15 become vulnerable to hypothermia and gastric erosion formation when food deprived and physically restrained on postnatal day 30 (S.H. Ackerman, M. A. Hofer, and H. Weiner, Science Wash. DC. 201: 373-376, 1978, and Gastroenterology 75: 649-654, 1978). We tested the hypothesis that this hypothermia is associated with a decrease in oxidative metabolism. We measured O2 consumption of 30-day-old rat pups that had been previously separated at either day 15 (15w) or day 21 (21w). When food was available, 15w rats used as much O2 as 21w rats. When rats were food deprived or food deprived and restrained, 15w rats used significantly less O2 than 21w rats, implying less heat production. We hypothesized that this decrease in heat production during food deprivation and/or restraint was due to impaired thermogenesis resulting from inadequate release of endogenous norepinephrine (NE), which is a stimulant of brown adipose tissue- (BAT) mediated thermogenesis. To test this hypothesis we administered exogenous NE to 15w to 21w rats. Exogenous NE failed to increase O2 consumption in 21w or 15w rats when injected during either food deprivation or restraint. We concluded that 30-day-old 15w rats have decreased oxidative metabolism during food deprivation and restraint and therefore become hypothermic. This decreased oxidative metabolism does not appear to be attributable to insufficient endogenous NE, since it is not reversed by the addition of exogenous NE. We suggest that a decrease in oxidative metabolism may explain susceptibility to stress ulcers in a number of previously reported experimental models. PMID- 2916698 TI - Sleep changes in emperor penguins during fasting. AB - The proportion and the distribution over 24 h of the different arousal stages characterized in emperor penguins [wakefulness (W), drowsiness (D), slow-wave sleep (SWS), and paradoxical sleep (PS)] were studied under natural ambient conditions in four subjects that were first fed and then deprived of food for 7 18 days. In both fed and fasting states, each arousal stage was distributed through numerous episodes of short duration. The fasting state provoked only a slight increase in D. There was, however, a large increase in SWS, which increased from 37.5 to 55.4%/day, mainly at the expense of W, which fell from 42.7 to 21.9%/day, in close relation to the first two fasting phases when proteins were saved and when most of the energy was derived from lipids. PS proportions were lower during fasting (from 5.7 to 2.4%/day). These changes in the arousal stages in emperor penguins are examined for their implications in sleep mechanisms and energy saving. Their possible consequences, due to the reduced alertness, are also discussed. PMID- 2916699 TI - Neuromodulation of intestinal transport in the suckling mouse. AB - The influence of enteric nerves on intestinal ion and sugar transport was investigated in 3- to 4-wk-old suckling mice. Whole thickness segments of jejunum were mounted as flat sheets in flux chambers equipped to electrically stimulate nerves in the intestinal wall. Tetrodotoxin significantly reduced basal short circuit current in a subset of tissues containing 3-O-methylglucose in the mucosal bath. Electrical field stimulation of intrinsic nerves evoked an increase in short-circuit current of 86 +/- 15 microA/cm2 that was due to an increase in active chloride secretion with no significant change in the net movement of other ions. The secretory response to neural stimulation was abolished by tetrodotoxin and reduced by the muscarinic antagonist, atropine. Mucosal-to-serosal fluxes of 3-O-methylglucose were not altered by the cholinergic agonist carbachol. These results show that ion transport in the suckling mouse jejunum is regulated by the enteric nervous system. Neural stimulation evokes a chloride secretory response that is mediated by acetylcholine and other noncholinergic transmitters. Sugar transport in the murine small intestine does not appear to be influenced by muscarinic cholinergic agonists. PMID- 2916700 TI - Hypertension and alterations in central catecholamines after preoptic recess lesions. AB - Catecholamine concentrations were measured in brain regions of rats with lesions of the anteroventral third ventricle (AV3V-X rats) or parietal cortex (CORT-X) and of control-operated (CONT) rats. Three hours after surgery, total norepinephrine (NE) concentrations in all brain regions measured of AV3V-X rats were less than those of CONT or CORT-X rats. Epinephrine (EPI) concentrations were decreased in the medulla and hypothalamus, but dopamine levels were unchanged. Also, extracellular NE concentration, estimated by in vivo microdialysis techniques, was increased in the anterior hypothalamic nucleus (AHNE) and dorsomedial medulla (DMMNE) of AV3V-X rats compared with CONT rats. Increased DMMNE paralleled blood pressure increases. DMMNE did not change after blood pressure was increased by intravenous angiotensin II infusion (60 ng/min) in CONT rats. Thus 1) AV3V lesions result in decreased NE and EPI concentrations in multiple brain regions; 2) acute reductions in central NE in AV3V-X rats are associated with increased extracellular NE in the AH and DMM, suggesting increased NE release; and 3) although increased DMMNE is temporally related to increased blood pressure following AV3V lesions, increased DMMNE is not a response to the hypertension per se. PMID- 2916701 TI - Adrenalectomy and response to corticosterone and MSH in the genetically obese yellow mouse. AB - Animals with the viable yellow (Avy/a) gene and their corresponding lean control black mice (a/a) were adrenalectomized or sham adrenalectomized, and changes in body weight, body composition, corticosterone, and GDP-binding to mitochondria isolated from interscapular brown adipose tissue (IBAT) were measured. Adrenalectomy slowed the weight gain of both the yellow obese mice and the black lean mice, but the reduction was greater in the yellow mice. Food intake was significantly reduced in the yellow mice. Adrenalectomy in the yellow mouse was associated with an increase in lean mass and a significant decrease in weights of fat depots. Blood glucose concentrations of the adrenalectomized yellow mice were reduced to levels similar to those of lean mice, but insulin levels, although lower than sham-adrenalectomized yellow mice, remained significantly higher than in lean animals. GDP binding to IBAT mitochondria increased after adrenalectomy in both phenotypes to values that were similar. Corticosterone replacement in adrenalectomized yellow mice produced a dose-dependent increase in body weight that was associated with a decrease in muscle weight and an increase in adipose tissue weight. Both desacetyl-melanocyte-stimulating hormone (MSH) and alpha-MSH interacted with corticosterone to increase body weight gain of adrenalectomized yellow mice. Desacetyl-MSH was more effective than alpha-MSH on increasing adipose tissue and liver weights. The effects of desacetyl-MSH on food intake, weight gain, and tissue weights were independent of the adrenal gland or of corticosterone. PMID- 2916702 TI - Structure and concentrating ability in the avian kidney. AB - We quantified various aspects of the morphology of the kidney in seven bird species and related these measures to urinary concentrating ability (the concentration of ureteral urine in dehydrated animals) for six of the species. Kidney mass, number of glomeruli, and number of medullary cones all tended to increase with body mass. Smaller birds, with smaller kidneys, had smaller nephrons with smaller glomeruli. Lengths of medullary cones tended to increase with body mass and were exceptionally long in the macaroni penguin. The proportion of nephrons that were mammalian-type (MT, with loops of Henle) ranged from 7% (ring-necked pheasant) to 30% (zebra finch, glaucous-winged gull) and was unrelated to kidney mass. The percent of kidney mass comprised of medullary cones varied from 5 to 13%, unrelated to kidney mass. The number of reptilian-type (without loops of Henle) nephrons associated with each medullary cone tended to increase with kidney mass. Of the variables examined, length of the medullary cones, and hence of the longest loops of Henle, was most strongly correlated with urinary concentrating ability; however, this correlation was negative. Concentrating ability was also strongly negatively correlated with body mass (small birds concentrate better). No significant relation existed between concentrating ability and proportion of MT nephrons. Our data suggest that, in a broad interspecific comparison, the quantitative extent of the renal medulla is not the primary determinant of urinary concentrating ability in birds. PMID- 2916703 TI - Amiloride effect on diurnal cyclic Na and K excretion in rats. AB - Amiloride was administered to rats during the peak and minimum of Na and K diurnal rhythmic excretion (i.e., during early dark phase and early light phase). In rats receiving a normal-K diet (2.34 meq/day) amiloride decreased K excretion from 186 to 37 mueq/h (dark phase) and from 31 to 4 mueq/h (light phase). Amiloride increased Na excretion from 91 to 344 mueq/h (dark phase) and from 35 to 164 mueq/h (light phase). Rats receiving a high-K diet (10.4 meq/day) showed a higher diurnal peak and minimum for K excretion. During high-K intake, amiloride decreased K excretion from 787 to 191 mueq/h (dark phase) and from 197 to 40 mueq/h (light phase) and increased Na excretion from 237 to 891 mueq/h (dark phase) and from 31 to 222 mueq/h (light phase). Whenever given, amiloride reduced K excretion to approximately 20% of control excretion. It is concluded that rhythmic changes in amiloride-sensitive distal transport are largely, but not entirely, responsible for the diurnal K cycle, but do not cause the concurrent Na cycle. Thus the diurnal cycles in Na and K are expressed through changes in different transport mechanisms. In rats maintained on a high-K diet there is an increase in rhythmic K secretion and Na reabsorption by amiloride-sensitive transport. To maintain Na excretion unchanged, Na reabsorption must be correspondingly depressed at an amiloride-insensitive site. PMID- 2916704 TI - Nocturnal patterns of macronutrient intake in freely feeding and food-deprived rats. AB - Analyses of rats' feeding behavior at the start and the end of the nocturnal cycle have revealed dramatic alterations in macronutrient intake over time. At dark onset, rats displayed a preference for carbohydrate, with the first meal of the night consisting of approximately 60% of this nutrient. This carbohydrate intake was soon followed by a shift toward protein-predominant meals. Superimposed on this pattern of meal-to-meal shifts in nutrient selection appears to be an additional rhythm in which carbohydrate ingestion was favored at dark onset and protein and fat ingestion were favored during the late dark hours. Differential feeding patterns were also apparent following mild food deprivation. A 2-h period of deprivation at dark onset produced a strong compensatory feeding response, particularly of fat and carbohydrate. This pattern was not observed at the end of the dark, when little compensatory feeding was demonstrated. It is suggested that these feeding patterns may be related to the activity of certain hypothalamic neurotransmitters, e.g., norepinephrine and serotonin, known to be important in modulating temporal feeding patterns and nutrient intake. PMID- 2916705 TI - Carotid baroreflex resetting during drug-induced arterial pressure changes in humans. AB - We studied human baroreflex resetting during 25 min of drug-induced arterial pressure changes in 10 healthy volunteers. Average (+/- SE) base-line systolic pressure of 113 +/- 4 fell to 102 +/- 3 during nitroprusside infusions and rose to 135 +/- 6 mmHg during phenylephrine infusions. Average base-line R-R intervals of 932 +/- 37 shortened to 820 +/- 39 during nitroprusside infusions and lengthened to 1,251 +/- 61 ms during phenylephrine infusions. Carotid baroreceptor-cardiac reflex responses were evaluated with a complex series of neck chamber pressure changes, and R-R intervals were plotted as functions of carotid distending pressure. Baroreceptor-cardiac reflex relations shifted on both R-R interval and arterial pressure axes during drug infusions, but there was no significant change of the maximum slope or range of R-R interval responses. The position of baseline R-R intervals on the reflex relation (operational point) changed significantly. Resting R-R intervals were closer to threshold during pressure reductions and closer to saturation for baroreceptor-cardiac responses during pressure elevations. These results document short-term partial resetting of human baroreceptor-cardiac reflex responses as early as 25 min after the onset of arterial pressure changes. PMID- 2916707 TI - Siphon mechanism in collapsible tubes: application to circulation of the giraffe head. AB - Controversy exists over the principles involved in determining blood flow to the head of a giraffe, specifically over the role of gravity pressure (pgh) in the collapsible jugular vein in facilitating uphill flow in arteries. This study investigated the pressures within vertically oriented models containing both rigid and collapsible tubes. An inverted U tube was constructed (height = 103 cm) of thick rubber tubing in the ascending limb and collapsible dialysis tubing in the descending limb. Water flow was induced by a variable speed pump maintained at the reservoir level such that the descending limb was partially collapsed. Pressure measurements were made at various levels within the U tube by two methods: 1) with the transducer at same level as the tip of the water-filled catheter and 2) with the transducer at the reservoir level. During flow, the pressure at any point was nearly atmospheric along the length of the descending limb. Such methods of obtaining pressure indicated that the pressure gradient within the partially collapsed descending limb was the sum of viscous flow pressure (P1-P2 of Poiseuille) and gravitational pressure (pgh). To study the facilitatory effect of a siphon, the descending limb was compared with a horizontally placed limb (length = 100 cm), and the flow was kept constant. Calculations of hydraulic "work" (pressure x flow) indicated that with a partially collapsed descending limb, work of the pump was reduced by 15% compared with uphill flow to the elevated horizontal position. It is concluded that the siphon mechanism operates in a partially collapsed descending limb of a siphon loop. PMID- 2916706 TI - In vitro diencephalic neuronal thermosensitivity in normotensive and hypertensive rats. AB - Because morphological differences exist in hypothalamic neurons from spontaneously hypertensive (SH) and normotensive Wistar-Kyoto (WKY) rats, the present study recorded neuronal spontaneous activity and thermosensitivity from diencephalic tissue slices of these two strains. With the use of extracellular recordings from horizontal tissue slices, neurons were characterized according to location, firing rate at 37 degrees C, and firing rate response to changes in local tissue temperature. Compared with WKY neurons, SH neurons had higher firing rates in the preoptic-anterior hypothalamus and lower firing rates in the dorsomedial hypothalamus. In addition, SH warm-sensitive neurons were less thermosensitive over the hyperthermic range (37-40 degrees C), and SH temperature insensitive neurons had higher spontaneous firing rates. These differences in spontaneous activity and thermosensitivity provide a neuronal basis to explain the elevation of core temperature observed in SH rats. PMID- 2916708 TI - Reducing the threat of hip fracture. PMID- 2916709 TI - Evaluating community interventions to reduce drunken driving. PMID- 2916710 TI - Injury control in perspective. PMID- 2916712 TI - Determinants of recovery 12 months after hip fracture: the importance of psychosocial factors. AB - The independent contributions to recovery from hip fracture of psychosocial factors including depression, personality, social connectedness, and self-rated health were studied in 219 women age 59 and older (mean age 78.5) who were community dwelling prior to fracture. Initial assessments were conducted shortly after surgery and follow up assessments 2, 6, and 12 months later. By 12 months, 15 patients had died and 15 had entered a nursing home. Substantial declines in physical functioning though not psychosocial status were observed. Only 21 per cent (compared to 81 per cent prefracture) reported walking independently; fewer than 30 per cent had regained reported prefracture levels of physical function. The proportion with elevated depression scores at 12 months was 20 per cent, down from 51 per cent following surgery; 64 per cent rated their health excellent or good at 12 months, up from 43 per cent after surgery. Poor cognitive status and post-surgical self-rated health were predictive of mortality. Among survivors, age, prefracture physical functioning, and cognitive status were associated with recovery in physical function but not psychosocial status. High post-surgery depression scores, but not the other psychosocial factors, were associated with poorer recovery in both functional and psychosocial status. These findings demonstrate the importance of depressive symptoms as one determinant of recovery from hip fracture and support the need to attend to the affective status of hip fracture patients following surgery. PMID- 2916713 TI - Traffic safety effects of sobriety checkpoints and other local DWI programs in New Jersey. AB - We examined the efficacy of three Driving While Intoxicated (DWI) programs in New Jersey from 1980 through 1985, using covariance analysis of county data. Road blocks, the major component of the Strike Force program, were associated with a drop of 10-15 per cent in the single vehicle nighttime crash rate and showed a relatively stable effect over time. DWI Task Force, an education program, was associated with a 6-10 per cent total decline in the crash rate and declining impact over time. SOBER, another education program, was associated with a small effect in the first year and little or no effect thereafter. PMID- 2916711 TI - Survival experience of aged hip fracture patients. AB - Hip fracture has long been considered a major threat to survival in aged populations. This report describes the survival experience of 814 aged, community dwelling hip fracture patients treated in seven Baltimore hospitals between 1984 and 1986: 4.3 per cent died during hospitalization; 8.2, 12.6, and 17.4 per cent died within three, six, and 12 months after fracture, respectively. The mortality rate for the entire population approaches expected mortality approximately six months post-fracture, but varies by age and sex. The most important factors predicting mortality are presence of serious concomitant illness and marked delirium (in the absence of dementia) at the time of hospital admission. The authors suggest that medical factors that may contribute to patient disorientation be investigated and treated, when possible, in an effort to improve the survival status of hip fracture patients. PMID- 2916714 TI - Blood alcohol tests, prevalence of involvement, and outcomes following brain injury. AB - We collected data on all residents of San Diego County, California who were hospitalized for or died from a brain injury in 1981. The objectives were to assess the frequency of blood alcohol concentration (BAC) testing and the associations of BAC prevalence with the external cause of the brain injury and case outcome. We found that high BAC levels were most frequent among brain injured subjects between the ages of 25 and 44 and among those subjects involved in motor vehicle crashes and assaults. Contrary to expectations, injury severity and hospital mortality were inversely related to BAC level, controlling for other predictors. We believe that these inverse associations might be due to differential rates of BAC testing by severity. Among brain-injured survivors with more severe injuries, however, we found that BAC level was positively associated with the prevalence of physician-diagnosed neurological impairment at discharge and with the length of hospitalization. PMID- 2916715 TI - Risk of fatal rollover in utility vehicles relative to static stability. AB - The risk of fatal rollover of utility vehicles per 100,000 registered vehicles relative to cars during 1982-87 was strongly correlated to the static stability of the vehicles. Distance between the center of the tires divided by twice the height of center of gravity explained 62 per cent of the variation in fatal rollover rates where rollover was the first harmful event. Statistical controls for 20 major risk factors indicated no correlations that would deflate the correlation between stability and rollover. Low stability utility vehicles roll over more often on the road suggesting that the lateral force of turning is often the tipping force. PMID- 2916716 TI - Evaluation of the efficacy of simulation games in traffic safety education of kindergarten children. AB - Using a simulation game designed to teach children to obey certain traffic safety rules, an experimental study was conducted with 136 five-year-old children in four Quebec schools. Within each classroom, subjects were randomly divided into four groups: three intervention groups and one control group. Each of the experimental groups was subjected to a different intervention with outcome measured using three instruments related to attitudes, behavior, and transfer of learning of pedestrian traffic safety. Results suggest that simulation games including role-playing/group dynamics and modeling/training can change attitudes and modify behavior in the area of pedestrian traffic safety in children of this age. PMID- 2916717 TI - Childhood injury deaths: national analysis and geographic variations. AB - Twenty-three causes of injury mortality in children ages 0-14 in the United States were analyzed by age, race, sex, and state of residence for the years 1980 85. Motor vehicles caused 37 per cent of all injury-related deaths and were the leading cause of injury mortality in every group except children younger than one year, for whom homicide was the leading cause. Male death rates were at least four times female rates for suicide, unintentional firearm injury, and injuries related to farm machinery or motorcycles. The drowning rate among Whites was almost twice that of Blacks for ages 1-4, but in the 10-14 year age group the drowning rate for Blacks was over three times that of Whites. In general, the highest injury death rates were in the mountain states and the south. Between 1980 and 1985, the suicide rate in the 10-14 year age group more than doubled. PMID- 2916718 TI - Incidence, causes and severity of injuries in Aquitaine, France: a community based study of hospital admissions and deaths. AB - This paper reports the results of a study of injuries conducted during a one-year period within a defined geographic population of 2.7 million persons (Aquitaine, France). Cases were defined as unintentional or intentional injuries, either resulting in immediate death before reaching hospital or requiring hospital admission. During the one-year period, 1,181 deaths were registered and 8,190 hospital admissions occurred during the sample periods. The three leading causes of injury were falls (40 per cent), traffic accidents (27 per cent), and poisonings (15 per cent). The overall incidence of injuries was 136 per 10,000 person years. Incidence by sex and age was assessed for the main external causes. The ratios of nonfatal to fatal cases were calculated by sex and age and by external cause. The origin of the injury was suicide in 14 per cent of cases and assault or homicide in 3 per cent. The severity of injuries, assessed using an automatic computation of the Injury Severity Score (ISS), ranged from 1 to 66 with a mean of 6.9. Substantial variations of ISS were observed according to external cause. At the 8th day following admission, 31 per cent of hospital treated patients were still hospitalized and 0.8 per cent had died in hospital. The outcome correlated well with the ISS. PMID- 2916720 TI - Driver age and crash involvement. AB - The youngest and oldest drivers have the highest crash risk, but the problem lies predominantly in the youngest age groups because elderly drivers have low exposure. The elderly driver problem will increase gradually as their share of the population increases but will remain relatively small. The bulk of the problem will continue to reside among drivers younger than age 65, particularly the youngest drivers. PMID- 2916719 TI - Sport fish consumption advisories and projected cancer risks in the Great Lakes basin. AB - Because Great Lakes sport fish are contaminated with several toxicants, the Great Lakes states individually issue advisories, principally based on Food and Drug Administration (FDA) action levels, that suggest limiting or eliminating consumption of contaminated fish. We describe the procedures the states use to determine when to issue consumption advisories and we evaluate the associated cancer risks using EPA-IARC-OSTP risk assessment procedures. Projected cancer risks are high for consumers of small quantities of sport fish contaminated with DDT or dieldrin at their respective action levels. Projected risks at concentrations that are common but below the action levels are also substantial. We propose that sport fish with tissue concentrations of DDT or dieldrin one fifth and one-third of the action levels should be covered by consumption advisories to warn consumers of the potential adverse health impacts. PMID- 2916721 TI - The inaccessibility of seat belts in taxicabs. AB - The accessibility of seat belts was determined in a total sample of 200 taxicabs waiting to pick up passengers at eight city airports. A rear seat belt was "accessible" (able to be fastened within 10 seconds) in 111 (55.5 per cent) taxicabs. The proportion varied by city from 16.0 per cent (New York City) to 96.0 per cent (Minneapolis-St. Paul) and was higher for taxicabs in cities covered by mandatory state seat belt legislation. PMID- 2916722 TI - Coverage gaps in seat belt use laws. AB - Some seat belt use laws exempt occupants in certain seating positions and in certain types of vehicles, or both. A state-by-state analysis was conducted of the extent to which passenger vehicle occupants killed before the laws went into effect would have been covered by the laws subsequently passed. Only five states had laws that covered all passenger vehicle occupants; the majority excluded 4 to 8 per cent and six states excluded 14 per cent or more. More inclusive laws can reduce injuries and save lives. PMID- 2916723 TI - Reducing knee morbidity among carpetlayers. AB - Carpetlayers have a high prevalence of occupational knee morbidity, partly attributable to their use of the knee kicker to stretch carpet for wall-to-wall installation. While a mechanical alternative "power stretcher" is available, knee kickers are still widely used. A questionnaire survey indicated that unavailability of the mechanical stretcher at installation sites was a major factor for continued use of the knee kicker. Strategies to reduce use of the knee kicker are discussed. PMID- 2916725 TI - Project LEAN. PMID- 2916724 TI - Modeling and variable selection in epidemiologic analysis. AB - This paper provides an overview of problems in multivariate modeling of epidemiologic data, and examines some proposed solutions. Special attention is given to the task of model selection, which involves selection of the model form, selection of the variables to enter the model, and selection of the form of these variables in the model. Several conclusions are drawn, among them: a) model and variable forms should be selected based on regression diagnostic procedures, in addition to goodness-of-fit tests; b) variable-selection algorithms in current packaged programs, such as conventional stepwise regression, can easily lead to invalid estimates and tests of effect; and c) variable selection is better approached by direct estimation of the degree of confounding produced by each variable than by significance-testing algorithms. As a general rule, before using a model to estimate effects, one should evaluate the assumptions implied by the model against both the data and prior information. PMID- 2916726 TI - Pleomorphic fibroma of the skin: a benign neoplasm with cytologic atypia. A clinicopathologic study of eight cases. AB - A clinicopathologic study of eight examples of polypoid and dome-shaped cutaneous fibrous lesions with sparse cellularity but striking nuclear atypia and rare mitotic figures is presented. Positive immunohistochemical staining for vimentin and actin supported the fibroblastic nature of these lesions. All eight cases were adults whose ages ranged from 33 to 67 years (mean 52 years). Five were women and three were men. Five lesions were located on extremities, two on the trunk, and one on the face and they measured from 4 to 16 mm in greatest dimension. The lesions were clinically followed from 4 months to 5 years. They all showed benign clinical behavior, with only one local recurrence in a lesion that had been incompletely removed. The nuclear atypia seen in these fibrous lesions may be similar to that which occurs in other benign mesenchymal neoplasms, such as pleomorphic lipoma, pleomorphic leiomyoma, ancient schwannoma, and variants of dermatofibroma with atypical cells. We suggest that "pleomorphic fibroma" is an appropriate term for this lesion based on its histologic differentiation, cytologic atypia, and benign clinical course. PMID- 2916728 TI - Ploidy and condylomata. PMID- 2916727 TI - Pulmonary metastases in patients with low-grade endometrial stromal sarcoma. Clinicopathologic findings with immunohistochemical characterization. AB - Two cases of low-grade endometrial stromal sarcoma (ESS) presenting as cystic pulmonary metastases are reported. Both lung lesions were initially thought to represent examples of so-called mesenchymal cystic hamartoma. A diligent search of the past medical records in the first case revealed that a primary low-grade ESS of the uterus had been resected 27 years earlier. In the second case, a uterine tumor was seen by computed tomography scan and subsequent pathologic examination of the hysterectomy specimen established the presence of a low-grade ESS. Peritoneal metastases, present in both cases, also presented diagnostic problems until the uterine primaries were recognized. Immunoreactivity for desmin was detected in all primary and metastatic tumor sites examined. We conclude that ESS should be included among the desmin-positive spindle cell sarcomas and that metastatic ESS should be included in the differential diagnosis of "benign" mesenchymal cystic hamartoma of the lung. PMID- 2916729 TI - Follow-up in gastric dysplasia patients. PMID- 2916730 TI - Ultrastructural biology of Leishmania (Viannia) panamensis (=Leishmania braziliensis panamensis) in Lutzomyia gomezi (Diptera: Psychodidae): a natural host-parasite association. AB - The development of Leishmania (Viannia) panamensis in a natural sand fly host, Lutzomyia gomezi, was studied by light and transmission electron microscopy. New aspects of peripylarian parasite behavior and morphology in the sand fly gut, early bloodmeal stages, and ultrastructural development in the anterior gut were documented. Eight distinct morphological forms were observed in the life cycle of the parasite within the insect. In the bloodmeal, amastigotes (1) transformed into stumpy promastigotes (2) which rapidly multiplied, resulting in spatulate shaped nectomonad promastigotes (3) and elongate nectomonad promastigotes (4). These latter forms migrated primarily into the hindgut, where both were observed attached (=haptomonad phase) to the cuticular intima by hemidesmosomes within extremely shortened flagella. Spatulate haptomonad promastigotes predominated, colonizing the entire length of the hindgut, with the greatest density at 2 disjunct sites: the pylorus/ileum and the anterior rectum/rectal sac. Paramastigotes and dividing flagellates were rare. Some parasites migrated directly to the cardia/stomodeal valve region without a hindgut phase; however, major movement anteriorly was from the hindgut beginning at 6 days postinfection. In the cardia lumen, dividing short Type A promastigotes (5) predominated, intermixed with short Type B promastigotes with longer flagella (6). Paramastigotes (7) were free-swimming in the lumen as well as attached to the stomodeal valve. The primary colonizers of the valve were pear-shaped haptomonad promastigotes (8), with flagella of variable lengths and multi-segmented hemidesmosomal attachment points to the intima. Promastigotes and paramastigotes colonized the esophagus-pharynx region and attached to the foregut lining by flagellar hemidesmosomes. Both forms may represent infective stages of L. (V.) panamensis; however, no parasites were detected in the cibarium or proboscis. L. (V.) panamensis appeared well-adapted to the gut of Lu. gomezi, multiplying extensively at 2 sites, changing morphological form, and adhering to host surfaces by variously modified flagellar hemidesmosomes. PMID- 2916731 TI - Co-circulation of multiple Colorado tick fever virus genotypes. AB - Colorado tick fever (CTF) virus, family Reoviridae, genus Orbivirus, contains 12 genes distinguishable by polyacrylamide gel electrophoresis (PAGE). Multiple genotypes of CTF virus were isolated at 3 field sites in Colorado in 1985. Five genotypes were found at Campos Cabin, 2 at Drake, and 6 at Rocky Mountain National Park. Virus isolations were made in 1985 from 6 patients with CTF. These isolates were distinct from each other and the field isolates. Although the CTF isolates were different by PAGE profile, the majority of the 12 genes were highly conserved among the 1985 isolates and a Florio isolate (FMA). Only genes 4 and 6 were variant among the 1985 CTF isolates and FMA, and no unique genes were identified. In 1986, a follow-up field survey was done at the Campos Cabin site. Of the 3 CTF PAGE genotypes obtained, 2 exhibited PAGE profiles which were different from the 1985 isolates. One isolate may have resulted from the reassortment of genes from 2 of the isolates circulating at Campos Cabin in 1985. PMID- 2916732 TI - Here we are: behind again! PMID- 2916733 TI - The tension-free hernioplasty. AB - Since the first true herniorrhaphy was performed by Bassini over 100 years ago, all modifications and surgical techniques have shared a common disadvantage: suture line tension. The anatomic, physiologic, and pathologic characteristics of hernia recurrence are examined. The prime etiologic factor behind most herniorrhaphy failures is the suturing together, under tension, of structures that are not normally in apposition. With the use of modern mesh prosthetics, it is now possible to repair all hernias without distortion of the normal anatomy and with no suture line tension. The technique is simple, rapid, less painful, and effective, allowing prompt resumption of unrestricted physical activity. PMID- 2916734 TI - Implantation metastasis as a cause of local recurrence of colorectal carcinoma. AB - Local recurrence of colorectal carcinoma postoperatively is due to locally unresected tumor, lymphatic permeation by tumor, or intraoperative implantation of viable shed cancer cells. One hundred eighty-five patients with colorectal carcinoma underwent resection for cure. Of these patients, 40 received diluted formalin intraluminally for prevention of local recurrence, and the remainder received no cancericidal agent. Distribution by tumor size and stage was similar in both groups. Local recurrence occurred in 2.6 percent of formalin-treated patients and 14.3 percent of untreated patients. The difference in recurrence rates was significant (p less than 0.05). No significant difference between the two groups was present in the actuarial survival curves. The 5-year survival rate was 66.6 percent in the formalin-treated group and 50.5 percent in the control group. No suture line recurrences were observed in the treated group. Our results indicate that intraluminal fixation of cancer cells before opening the bowel is an effective method of reducing local recurrence after resection of colorectal cancer. PMID- 2916735 TI - Early gastric cancer. AB - Thirty-six patients with early gastric cancer were studied. In 15 patients, malignancy was restricted to the mucosa; in 21 patients, submucosal invasion was noted. Lymph node involvement was found in four patients. Kaplan-Meier estimates for 5-year survival were 92 percent for mucosal lesions and 65 percent for submucosal lesions (overall 5-year survival rate 73 percent). Mucosal lesions were significantly larger than were submucosal lesions (3.7 +/- 0.6 cm versus 2.5 +/- 0.4 cm, mean +/- SE; p less than 0.005). Associated malignancy was recorded in 13 of 36 patients. When compared with data from a large Japanese study, early gastric cancer in the United States tends to develop more distally in the stomach and in patients approximately one decade older. Survival was not as favorable as in Japan. This may be related to patient age and the high incidence of associated nongastric malignancy. PMID- 2916736 TI - Screening for cholelithiasis prior to aortic reconstruction. AB - A study was undertaken to determine the value of preoperative oral cholecystography and the incidence and complications of cholelithiasis in patients undergoing aortic reconstruction. Over an 11-year period, 785 patients underwent aortic reconstruction. Forty-seven had a previous cholecystectomy; of the 738 remaining patients, 394 underwent preoperative operative oral cholecystography to screen for cholelithiasis. Seventy-three (18 percent) were found to have gallbladder disease. Thirteen had symptoms attributed to cholelithiasis and underwent cholecystectomy with aortic reconstruction. Three hundred eighty-one were left with the gallbladder after aortic reconstruction, 60 in whom disease was identified and 321 with normal oral cholecystography results. Three patients developed cholecystitis in the postoperative period, one in the diseased group and two with normal gallbladders. The incidence of postoperative cholecystitis was 0.8 percent (3 patients). Preoperative oral cholecystography is of little value as a screening tool. Cholecystectomy during aortic reconstruction is probably safe and the risk of postoperative cholecystitis in the asymptomatic patient is negligible. PMID- 2916738 TI - External carotid endarterectomy under direct vision. AB - At the conclusion of standard carotid endarterectomy in 50 consecutive patients, we examined flow in the external carotid artery using a continuous-wave Doppler probe. In two patients (4 percent), flow was absent in the distal external carotid artery. In both patients, opening the external carotid artery through a separate incision revealed an obstructing intimal flap that was removed easily under direct vision, and external carotid endarterectomy was accomplished without interrupting flow through the internal carotid artery. This simple manuever allows for salvage of external carotid arteries that are occluded during standard blinded external carotid endarterectomy. PMID- 2916737 TI - The tracheoesophageal diversion and laryngotracheal separation procedures for treatment of intractable aspiration. AB - Intractable aspiration is a severe and often fatal complication in patients with impaired protective function of the larynx. This problem is usually a result of central nervous system disorders such as cerebrovascular accident, trauma, neoplasms, or degenerative disease. Surgical separation of the upper respiratory tract from the digestive tract can prevent recurrent contamination of the respiratory system in these patients. Two such procedures are the tracheoesophageal diversion procedure and a modification of this operation, the laryngotracheal separation procedure. The Virginia Mason Medical Center experience with these procedures, their indications, technique, and outcome are presented. In addition, cases of successful surgical reversal of the diversion procedures are discussed. PMID- 2916739 TI - An analysis of the fourth year of medical school for students pursuing surgical careers. AB - A fourth-year curriculum survey was forwarded to surgery resident program directors, clerkship directors, and residents. A 37 percent response rate was achieved with comparable representation of each respondent type from 130 institutions. The purpose of the survey was to determine how each of the 3 respondent types rated the importance of 42 subjects or clinical experiences to be taken in the fourth year of medical school for students pursuing surgical careers. The survey also included questions on such issues as externships, early match programs, and guidelines used at their institutions for their fourth year students. The results indicated a significantly high agreement among respondent types on what should comprise surgical students' fourth-year curriculum content. The majority feel the fourth year should be planned by students with an electives advisor to equally add breadth to their general professional education as well as provide prerequisite experiences in the career-chosen discipline. PMID- 2916740 TI - Staging for breast carcinoma. AB - Pretreatment staging and posttreatment follow-up of the breast cancer patient consists of physical examination of the breasts and regional node-bearing areas, routine laboratory studies, chest radiography, and bilateral mammography. For palpable tumors, mammography is used to determine tumor size and to identify nonpalpable multifocal or contralateral lesions. Mammography is an important adjunct to physical examination when monitoring for local recurrence in the irradiated breast or when searching for second primary cancers in the contralateral breast. Axillary nodes are evaluated by direct palpation, but some investigators recommend lymphoscintigraphy to examine the internal mammary chain. The most common sites for distant metastases are the skeleton, lung, brain, and liver. Although radionuclide scanning is currently the most effective method to evaluate metastases to bone, plain radiography, and sometimes computed tomography and magnetic resonance imaging, are required to corroborate radionuclide findings. However, due to cost constraints and anticipated low yield, routine imaging for metastases should be limited to chest radiography. PMID- 2916741 TI - Bowel obstruction after operation for colorectal carcinoma. PMID- 2916742 TI - Histopathology of congenital pigmented nevi. AB - Between 1982 and 1985, a total of 39 congenital pigmented nevi (CN) were removed from patients in the Oklahoma Children's Memorial Hospital. Multiple sections were examined from each of the lesions removed. The histologic patterns were recorded with special note of those features traditionally associated with CN. These include nevus cells in the lower reticular dermis and subcutaneous tissue, association of nevus cells with and in appendageal structures, and infiltration of nevus cells between collagen bundles. These features were primarily observed in larger CN (greater than 3 cm). Most small nevi do not show these features. The histologic patterns were consistent throughout multiple sections of the nevi. It is concluded that the histology traditionally associated with CN relates primarily to the size of the nevus rather than to the time of its appearance. PMID- 2916743 TI - Rhabdomyomatous mesenchymal hamartoma of skin. AB - A case of a solitary mesenchymal hamartoma occurring on the chin of a newborn infant is presented. The skin nodule exhibited an abnormal arrangement of dermal mesenchymal elements and, in particular, there was prominence of skeletal muscle. This lesion, which appears to be unique, has been termed rhabdomyomatous mesenchymal hamartoma of skin. PMID- 2916744 TI - Let's put it this way. A medical writing clinic. PMID- 2916745 TI - On the terminology of cutaneous melanoma. PMID- 2916746 TI - The nature of the cells comprising tactile corpuscle-like structures. PMID- 2916747 TI - On cell contribution to gonadal soma formation in quail-chick chimeras during the indifferent stage of gonadal development. AB - A quail mesonephros was produced in a chicken embryo by orthotopic transplantation of quail left Wolffian duct and intermediate mesoderm between somites 18 and 21 in a 2 day chicken embryo. During the indifferent period of gonadal development in the chicken (day 4-6), no mesonephric (quail) cells take part in forming gonadal somatic cells. At this period all these cells are derived from the surface epithelium. The epithelial cells leave the surface where colonization of primordial germ cells occurs. The mesonephros begins its participation in gonadal soma formation between day 6 and 7, the time of sexual differentiation. These results are discussed in terms of sexual differentiation and the development stage of the mesonephros. PMID- 2916748 TI - Morphofunctional study of mammotropic cells following intraventricular administration of met-enkephalin. AB - An ultrastructural and morphometric study was carried out on the adenohypophyseal mammotropic cells of rats treated intraventricularly with an acute dose (150 micrograms) of Met-enkephalin. In the female rats, clear features of cellular hyperactivity appeared after opioid administration. The changes affected the Golgi complex, the rough endoplasmic reticulum, the mature and immature secretory granules and the images of exocytosis. Such changes did not appear when naloxone was administered before the opioid, and naloxone induced an increase in the numerical density of lysosomal dense bodies with lipoid inclusions. In the male animals, administration of an identical dose of Met-enkephalin caused only a few significant changes, similar to those observed in the controls. It is concluded that Met-enkephalin administered intraventricularly causes evident modifications in the mammotropic cells of female rats whereas such changes in the male animals are not significant. PMID- 2916749 TI - Administration of bovine superoxide dismutase prevents sequelae of spinal cord ischemia in the rabbit. AB - The contribution of free radical-mediated reperfusion injury to the ischemic damage caused by total arterial occlusion has been investigated in a model of transient spinal cord ischemia in the rabbit. Spinal cord ischemia was produced in 20 anaesthetized rabbits by temporary luminal occlusion (20 min) of the abdominal aorta below the renal arteries. Superoxide dismutase (5 mg/kg) (10 animals) was infused before and during reperfusion below aortic occlusion using an infusion pump that infused the enzyme through the contralateral femoral artery. Control (10 animals) received sterile saline with the same procedure. In this later group, 4 animals developed paraplegia, 4 were paretic and only 2 were normal. However, in the treated group, 6 animals were normal while 3 were paretic and only one appeared paralyzed. We conclude that: a) oxygen free radicals generated during reperfusion are involved in producing the ischemic injury, and b) the ischemic spinal cord injury is prevented by superoxide dismutase. PMID- 2916750 TI - The fate map of the chick forelimb-bud and its bearing on hypothesized developmental control mechanisms. AB - Carbon particles and isotopic quail grafts were used as markers to study the salient features of the fate map of the chick forelimb between stages 20 and 27. The grafting technique confirmed the reliability of the carbon method: they both revealed striking asymmetries in which apical mesodermal tissue was progressively displaced in a proximal direction (as would be expected on the basis of growth by net apical addition of tissue) but also in a preaxial direction, while postaxial tissue became elongated in the direction of limb outgrowth. Ectoderm showed a similar preaxial-postaxial asymmetry but became displaced from initially underlying mesoderm. In marked contrast to mesoderm, distal ectoderm remained at a constant distance from the apical ectodermal ridge (or became incorporated into it), thus implying that the ectodermal sheet is anchored distally and grows by uniform stretching proximally. Within the ectoderm itself, the outer peridermal layer is displaced distally relative to the underlying epidermal basal layer. Peripheral mesoderm showed patterns of displacement which were intermediate between those of ectoderm and chondrogenic core mesoderm. It is argued that such morphogenetic phenomena are integral components of developmental mechanisms of significance in the control of pattern generation. Implications of the interpretation and use of the fate map in relation to theories of limb development, particularly those based on mechanisms defined in terms of limb axes, are reviewed. PMID- 2916751 TI - Hyaline-cell cartilage (chondroid) in the heads of teleosts. AB - The structure and distribution of hyaline-cell cartilage (chondroid) (HCC) in the heads of teleosts has been studied in 48 species from 16 families. The tissue is pale-staining and has closely-packed, hyaline cells that are separated by a small quantity of matrix. The matrix has only a mild affinity for alcian blue and the cells are not shrunken within lacunae. Two subtypes of the tissue are here described--fibrohyaline-cell cartilage (chondroid) where collagen fibres are prominent in the matrix, and lipohyaline-cell cartilage where fat and hyaline cells are intermingled. An elastic hyaline-cell cartilage has been described previously. Associations of HCC with dense fibrous connective tissue, mucochondroid, hyaline cartilage and bone are described. Lists are provided of membrane and cartilages bones to which the tissue is attached and of species in which it is common. Suitable 'type examples' for reference and for further study include the cartilage in the rostral folds of the red-tailed black shark, Labeo bicolor and the flying fox, Epalzeorhynchus kalopterus. HCC occurs in lips and rostral folds, in pre-palatine and submaxillary menisci, in ligaments, at the anterior end of the basihyal, in the pectoral girdle, in adhesive discs, in gill arches, beneath the basioccipital chewing pad, in barbels, next to the facial nerve, around the olfactory region and in the core of the nasal skin flaps. It is a particularly important tissue in cyprinids and related fish, and enormous masses of it are present in the black shark, Morulius chrysophekadion and the Hong Kong pleco, Pseudogastromyzon myersi. It acts as a damper against the contractions of the heart or the pressure of occluding pharyngeal teeth, and it provides the mouth region of bottom-dwelling, algal eaters with flexible support. In relation to Schaffer's classification of supporting tissues, I confirm a distinction between HCC and Zellknorpel. PMID- 2916752 TI - Origin of the notochord in the rat embryo tail. AB - The origin of the notochord in the rat tail was investigated on transverse serial semi-thin and ultra-thin sections of 12- and 13-day embryo tails. It was found that the notochord develops from a mass of condensed mesenchymal cells which is located ventrally to the secondary neural tube, and which subsequently splits into a) a thin cord which becomes notochord and b) a thick portion which gives rise to the tail gut. By analogy with the secondary neurulation and the secondary gut formation, one might therefore speak of a secondary notochord formation in the tail. It occurs in close relationship with the formation of the tail gut. PMID- 2916753 TI - Granular epithelioid cells of the kidneys in salmon adapted to fresh- and seawater. AB - The occurrence of granular epithelioid cells in the kidney arterial vessels was studied in one- and two-year-old Atlantic salmon during the physiological fresh- and seawater periods. The purpose of this study was to make long-term comparison on the morphology of the renin angiotensin system in the same fish species. One year-old salmon living in freshwater had a statistically significant higher number of granular epithelioid cells (39.9 +/- 8.3/mm arterial vessel) than the two-year-old fish living in seawater (29.8 +/- 5.2/mm arterial vessel, P less than 0.00001). There was also a significant difference from month to month between the groups (P less than 0.05), but not within the groups (P greater than 0.07 freshwater, P less than 0.3 seawater). With the electron microscope the granules were found evenly distributed within the cytoplasm. They were of high electron density and lined by a single membrane. The granules were composed of a finely granular material. The recorded data on length and weight showed that all fish ate and developed normally. From our results and the available literature, we conclude that in primitive vertebrates, the renin angiotensin system is primarily involved in renal circulation, with vasoconstriction on the afferent side of the glomerulus. PMID- 2916754 TI - Site-specific regulation of osteogenesis: maintenance of discrete levels of phenotypic expression in vitro. AB - Intrinsic differences in bone formation rate, cell numbers, and the percentages of cells expressing alkaline phosphatase activity were studied in explants of chick calvaria periosteum cultured for 4 days and 6 days. Proliferation, differentiation, and bone production were examined in radioautographs of plastic sections and by using whole-culture biochemical assays of protein and alkaline phosphatase. Ectocranial explants at both 4 days and 6 days exhibited more alkaline phosphatase-positive cells and significantly more bone formation than endocranial cultures. There were no detectable differences in cell numbers or 3H thymidine labeling indices. The volume of bone synthesized per osteoblast was significantly higher in the ectocranial group. Examination of bone stripped of periostea and then cultured for 4 days revealed that large areas of bone were covered by osteoblasts, indicating that the periosteal explant cultures were composed almost exclusively of osteoprogenitor cells and fibroblasts. The data suggest that the level of expression of predetermined osteogenic phenotypes can be maintained in vitro for 6 days following explantation and that variations in the rate of osteogenesis are programmed into progenitor cells prior to their differentiation into osteoblasts. PMID- 2916755 TI - Immunogold distribution of actin during spermiogenesis in the rat, hamster, monkey, and human. AB - The localization of actin during spermiogenesis in the rat, hamster, monkey, and human was examined at the ultrastructural level using postembedding immunogold methods. Results revealed a similar pattern of actin distribution in these four species, although the staining intensity was higher in rodent spermatids than in those obtained from primates. Gold particles were first detected in the nascent subacrosomal space of round spermatids. This subacrosomal labeling extended as the acrosome spread over the nucleus during the elongation phase, remained unchanged during the first steps of the maturation phase, and disappeared completely before spermiation. Thus, using antiactin probes (present results) and other specific probes, actin appears to be a consistent component of the subacrosomal layer of spermatids during the greater part of spermiogenesis in many mammals. PMID- 2916756 TI - Distribution of fibronectins and laminin in the early pig embryo. AB - Fibronectins (FN) and laminin (LN) distributions were studied in the pig embryo by indirect immunofluorescence using antiporcine FN and antimurine LN antibodies. Extracellular FN are first detected in the early blastocyst before endodermal cell migration. They appear between the cells and on the blastocoelic face of the inner cell mass; thus, they are located at the interface of the trophectoderm and extraembryonic endoderm. Mesodermal cells migrate in a tridimensional network of fibrillar FN. These glycoproteins are also in the extraembryonic membranes (chorion and yolk sac wall) contiguous to the FN-rich basement membranes of embryonic ectoderm and endoderm. Extracellular LN appears in the blastocyst when the endoderm is already established as a continuous cellular monolayer, and is located between the trophectoderm and the extraembryonic endoderm, which produces it. Laminin also accumulates at the basal surface of the embryonic ectoderm at the onset of gastrulation. In the extraembryonic membranes, LN appears at the interface of the endoderm and mesoderm and at the interface of the trophectoderm and mesoderm. It is produced and secreted by extraembryonic mesodermal cells. Analysis of the distribution of these glycoproteins suggests that FN allow the migration of endodermal and mesodermal cells by providing them with a suitable substrate. When these cells become immobilized, they synthesize LN, probably to stabilize their interactions with the underlying extracellular material and epithelia. PMID- 2916757 TI - Localization of fibronectin in megakaryocytes of fetal liver. AB - Antibodies specific for fibronectin were utilized to determine the sites of localization in the liver during development. The livers of fetal rats from each of gestation days 11-19, and from days 1 and 8 postpartum, were studied by fluorescence microscopy. Fibronectin was localized predominantly in megakaryocytes and megakaryocyte precursors, and to a lesser extent in the extracellular matrix surrounding blood vessels and between hepatocytes and sinusoids. The cytoplasm of megakaryocytes and their precursors displayed bright fluorescence but their nuclei were negative for fibronectin. Hepatocytes had negative or faint fluorescence. Megakaryocytes were present in the liver from day 12, and were numerous from day 13 through most of the rest of gestation. The relative numbers of megakaryocytes decreased in later gestation; at 8 days postpartum only a few were observed per section. Hepatic megakaryocytes appeared before megakaryocytes were established in spleen and bone marrow. The early and persistent high levels of fibronectin in hepatic megakaryocytes, in the absence of comparable localization within hepatocytes, leads us to the hypothesis that megakaryocytes are important in establishing circulating fibronectin levels in the fetus. Similarly, bone marrow megakaryocytes may contribute to circulating fibronectin in the adult. PMID- 2916758 TI - The ultrastructure of Ruffini endings in the periodontal ligament of rat incisors with special reference to the terminal Schwann cells (K-cells). AB - The Ruffini endings and associated cells in the periodontal ligament of rat incisors were investigated by means of immunohistochemistry for glia-specific S 100 protein and electron microscopy. Numerous Ruffini endings, which were immunoreactive for S-100 protein as well as for neurofilament protein, were distributed in the alveolus-related part of the lingual periodontal ligament. In electron microscopy, the Ruffini endings displayed expanded axoplasmic spines filled with a large number of mitochondria and neurofilaments; some of the spines directly contacted the surrounding collagen fibers via fingerlike projections. The axoplasmic spines and Schwann sheath, for the most part, were covered alternately by single or multiple layers of the basal lamina. Several rounded cells showing S-100 immunoreactivity occurred in the vicinity of the Ruffini endings. The rounded cells associated with Ruffini endings possessed a kidney shaped nucleus and enveloped the axoplasmic spines with their cytoplasmic processes. From these morphological features, the cells in question were identified as the K-cells described by Everts et al. (1977). These K-cells developed Golgi apparatus and rough endoplasmic reticulum, suggesting active synthesis of proteins. Immunohistochemistry at the electron microscopic level revealed an intense immunoreactivity for S-100 protein in the cytoplasm of the K cell and led to a conclusion that the K-cells were terminal Schwann cells associated with Ruffini endings, presumably corresponding to the lamellar cells in the inner bulb of sensory corpuscles. PMID- 2916759 TI - Can the parasternal long axis plane replace the apical four-chamber plane in diagnosing mitral valve prolapse? AB - Since the mitral anulus is now known to be saddle-shaped, use of the qualitative motion of the mitral valve (MV) leaflets in the apical four-chamber plane to diagnose mitral valve prolapse (MVP) may be unsound, in that superior systolic displacement of the MV leaflets would occur in normal subjects, as well as in patients with MVP. It has therefore been suggested that the parasternal long axis (PLAX) plane should be used to diagnose MVP. To test the feasibility of this approach, the authors examined the predictive accuracy of PLAX prolapse and other isolated echocardiographic abnormalities versus a multivariate decision tree approach. PLAX prolapse, which was significantly associated with marked (greater than 0.7 cm) apical four-chamber prolapse, mitral regurgitation, the presence of a thick mitral valve, and low relative body weight, was 100% specific for MVP but only 44% sensitive. Similarly, marked apical four-chamber prolapse was 100% specific but only 53% sensitive. Apical four-chamber prolapse, if gauged only qualitatively as present or absent, was 94% sensitive but only 50% specific. By contrast, the decision tree classified all 32 initial patients correctly, and in a second, test set, selected 6 additional patients; these 6 patients had many of the clinical features of MVP. These observations suggest that: (1) if prolapse is seen in the PLAX plane, the patient does have MVP; on the other hand, lack of prolapse in this plane does not exclude the diagnosis of MVP and (2) the apical four-chamber plane, used qualitatively, does not reliably distinguish patients with MVP from those without MVP. PMID- 2916760 TI - Arterial fibrodysplasia: a regional cause of peripheral occlusive vascular disease. AB - The authors studied 17 cases of symptomatic arterial fibrodysplasia involving peripheral arteries without concomitant renovascular hypertension in Iranian males (age range: twenty-two to forty-five years). Affected arteries were most commonly the femoral, iliac, and popliteal, but in 2 cases the axillary and brachial arteries were also affected. Three cases were progressive. Differential diagnosis of arterial fibrodysplasia is discussed. It is concluded that this entity is the most common cause of peripheral occlusive vascular disease in younger Iranian males. PMID- 2916761 TI - Ultrasonic treatment of varicose veins. AB - Varicose veins and venous ailments are common among adult Americans. Treatment procedures vary but are mostly invasive. The current investigation utilizes focused high-intensity ultrasound for producing destruction of the venous wall in experimental dogs and in patients with varicose veins. Results are encouraging and suggest that focused ultrasonic irradiation can be an efficacious means of treating varicose veins and other venous disorders. PMID- 2916763 TI - Simultaneous monitoring of electrocardiogram and arterial blood pressure during exercise-induced syncope in a patient with severe aortic stenosis--a case report. AB - A sixty-six-year-old man with severe aortic stenosis, in whom simultaneous and continuous monitoring of the electrocardiogram and arterial blood pressure was performed immediately before, during, and following recovery from exercise induced syncope, is reported. During exercise the patient developed anginal pain associated with a gradual fall of arterial blood pressure followed by syncope. At the onset of the syncope, arterial blood pressure was extremely low, and the electrocardiogram showed sinus tachycardia. It was assumed from these findings that profound hypotension, induced by peripheral vasodilatation and ischemic myocardial depression leading to inappropriately low cardiac output, was the underlying factor mainly responsible for the occurrence of exercise-induced syncope in the present case. PMID- 2916762 TI - Echocardiographic confirmation of mitral valve prolapse: a new finding on radionuclide ventriculography--a case report. AB - A prominent filling defect was depicted on a radionuclide ventriculogram in a patient with mitral regurgitation. This defect was later shown, by cardiac ultrasound, to be due to mitral valve prolapse into the left ventricle during diastole. This case illustrates that mitral valve prolapse should be added to the list of clinical entities that can result in an intraventricular defect on a radionuclide ventriculogram. PMID- 2916764 TI - Risk factors for coronary atherosclerosis in the elderly. AB - To determine the importance of traditional risk factors for coronary artery disease (CAD) in the elderly, the authors studied 64 consecutive patients with angiographically normal or near-normal coronary arteries and 64 patients with CAD. All patients were greater than or equal to sixty years old. The risk factors studied were male sex, hypertension, diabetes mellitus, hypercholesterolemia, cigarette smoking, sedentary life-style, and family history. The prevalence of these risk factors in the two groups of patients was compared. The results suggest that in persons greater than or equal to 60 years old, male sex and cigarette smoking continue to remain risk factors for CAD. Since most of the patients with diabetes and hypertension were on medical management for their condition, the authors' findings also suggest that diabetes mellitus, even under treatment, remains an important risk factor for CAD in the elderly but controlled hypertension does not. Other traditional risk factors (hypercholesterolemia, sedentary life-style, and family history) do not discriminate individuals with moderate to severe CAD from those with normal or near-normal coronary arteries in persons greater than or equal to sixty years old. PMID- 2916765 TI - Augmented fragmentation of atrial activity upon premature electrical stimuli by verapamil. AB - The significance of fragmented activity obtained from the atrium during electrophysiologic study (EP study) was confirmed since it was always observed just at the onset of fibrillation. It was preceded by extra stimuli or atrial flutter, and the initial site of fragmentation varied from case to case. The premature-stimulus-induced widening of the atrial wave was observed in some cases who had normal size of atrium and no heart failure. The widening was augmented by administration of verapamil but not by procainamide, suggesting that for such widening or fragmented activity, slow-fiber-mediated conduction seems to be responsible. One case with intraatrial reentrant tachycardia developed fragmentation lasting for 1.0 second after verapamil. Therefore, some apparently normal atria may have a subclinical electrophysiologic abnormality that can be disclosed by premature stimulations or verapamil. PMID- 2916766 TI - Is increased plasma viscosity a risk factor for high blood pressure? AB - Data from several epidemiologic studies have suggested that, among other variables, hematocrit and fibrinogen may constitute risk factors for high blood pressure. As part of a population survey for cardiovascular risk factors, plasma viscosity and hemoglobin were measured. Blood pressure was determined under standardized conditions according to the recommendations of the AHA. A two-stage age-sex-stratified cluster sample of 5,312 persons, aged twenty-five to sixty four years, was selected from a mixed urban/rural target population of 282,279 (total population approximately 533,000). A net response of 79.3% was achieved. Multiple logistic regression analyses including plasma viscosity, hemoglobin, body mass index, alcohol consumption, smoking behavior, and total serum cholesterol as independent variables were run controlling for both age and sex. Plasma viscosity appeared as a significant main effect in all analyses and demonstrated the strongest association with high blood pressure next to body mass index. Whether this association implies a causal relationship cannot be answered from cross-sectional data. However, even if plasma hyperviscosity represents a secondary phenomenon in hypertension, it might be of prognostic relevance. There is evidence that increased plasma viscosity may contribute to myocardial hypertrophy. Therefore hypertensives with impaired blood fluidity might constitute a subgroup at particular risk for cardiovascular complications. When antihypertensive drugs are selected, their influence on blood viscosity should be taken into account. PMID- 2916767 TI - The acute effects of cigarette smoking on treadmill exercise distances in patients with stable intermittent claudication. AB - The hypothesis that smoking has an acute effect on treadmill exercise performance in patients with peripheral vascular disease was investigated in a crossover trial. Twelve patients with stable intermittent claudication who were regular smokers attended on two occasions within one week and treadmill tests were performed after 1/2, 1, 1 1/2, and 2 hours. Immediately before the second exercise test, two standard cigarettes were smoked or an unlit cigarette was "sham-smoked." Because participants could not be blinded, an attempt to control for patient bias was made. Half were told that we expected smoking to make no difference or possibly cause some improvement, and half were told that we expected it to make no difference or possibly cause some deterioration. These explanations and the order of study days were determined by balanced randomization. Suggestion had a significant influence on claudication distance immediately after smoking (p less than 0.01) but no significant effect on walking distance. Combining data from both groups assumes that no overall bias was introduced by the explanations given. Immediately after smoking, small, nonsignificant increases in claudication distance (+10%, 95% CI-7%, +27%) and walking distance (+9%, 95% CI-2%, +19%) were observed. Smoking caused a mean increase in heart rate of 9 beats per minute, which persisted for one hour, but no consistent change in blood pressure. The results show that suggestion may have a significant influence on treadmill exercise distances. Smoking is unlikely to have an important acute effect on exercise performance in claudicants. PMID- 2916768 TI - Effects of glycosaminoglycans and protamine chloridrate on platelet aggregation induced by collagen and thrombin. AB - The effects of heparin (HE), dermatan sulfate (DS), heparan sulfate (HS) and protamine chloridrate (PC) on platelet aggregation were studied. Both PC and the three glycosaminoglycans (GAGs) did not influence collagen-induced platelet aggregation. In contrast, all the tested GAGs blocked thrombin-induced platelet aggregation. HE and HS were equivalent and very effective, while DS was also but to a lesser extent. This could be because HE and HS act via both antithrombin III and heparin-cofactor II, whereas DS exerts its action on the latter only. PC, too, inhibited, in a dose-dependent fashion, thrombin-induced platelet aggregation, probably by competing with the thrombin affinity binding sites on the platelet surface. When the GAGs were tested together with PC, HE was shown to be the most effective: on a weight-for-weight basis, an identical amount of PC was unable to counteract the inhibitory effect of HE, while it partially reversed those of DS and HS. A full reversal of the inhibitory effect of DS and HS was never observed, in spite of adding increasing amounts of PC. It seems likely that plasma components may preserve the bindings of such GAGs with their cofactors. PMID- 2916769 TI - Resting ankle-arm pressure index in vascular diseases of the lower extremities. AB - The authors calculated 442 values of resting ankle-arm indices in 222 patients, of whom 114 reported exercise pain of the lower extremities (51.3%) and 34 reported rest pain (15.3%). Tissue necrosis was diagnosed in 55 patients (24.8%) and other disorders in 19 (8.6%). Obliterating atherosclerosis was found in 186 patients (83.8%), Buerger's disease in 16 (7.2%), and other vascular diseases in 20 patients (9%). The studied index value in 262 examined lower extremities was 1.3-1.0 in 54, 0.9-0.8 in 29, 0.7-0.6 in 66, 0.5-0.4 in 55, and 0.3-0.0 in 58 lower extremities. Respective values for contralateral lower extremities (180) were the following: 69, 54, 33, 14, and 10. PMID- 2916770 TI - Brachial artery catheterization via cutdown and a direct needle puncture. AB - Brachial artery catheterization via cutdown and a direct needle puncture was evaluated in 369 patients undergoing arteriography at the authors' medical center from January, 1970, to March, 1988. The indications for retrograde brachial arteriography were absence of palpable femoral pulses, failure of a femoral approach, previous aortic bypass surgery, and/or aneurysms of the abdominal aorta. The technique and results are described. Two patients lost their radial pulse; 1 of them had thrombectomy and, one year later, developed an aneurysm at the site of the needle puncture. The authors conclude that catheterization of the brachial artery through direct needle puncture is a safe procedure with good results. PMID- 2916771 TI - Late cardiac deaths after isolated valve replacement for aortic stenosis. Relation to impaired left ventricular diastolic performance. AB - Sixty-three patients took part in a follow-up study ten to seventeen years after valve replacement for aortic stenosis. Data obtained were used to predict cardiac deaths (n = 14) occurring in the following three-year period. The degree of residual left ventricular (LV) hypertrophy correlated inversely with indices for LV systolic and diastolic performance (radionuclide cardiography). A logistic regression (LR) model had a positive predictive value for cardiac deaths of 100% (10/10) with 8% (4/53) false negatives. Evaluating LV performance indices exclusively, LR analysis showed that only peak filling rate had independent predictive value. Subnormal and normal LV ejection fractions were associated with equal three-year cardiac death rates (29%). Depressed LV function was related to residual hypertrophy. Impaired diastolic performance was the prime predictor of cardiac deaths. PMID- 2916772 TI - Abdominal aortic aneurysm with inferior vena cava obstruction: case report. AB - Behcet's syndrome, a multisystem disorder, is characterized by recurrent oral and genital aphthous ulcerations, eye lesions, and skin changes. Other manifestations, although rare, may affect the nervous, gastrointestinal, or locomotor system, as well as veins and arteries. Vascular lesions occur in approximately 30% of reported cases. Although thrombosis in the larger veins is frequent, arterial thrombosis is somewhat less likely to occur. Only a few cases of arterial aneurysm have been documented in the literature. This report describes a patient who had suffered from Behcet's syndrome for fifteen years and in whom a complete obstruction of the inferior vena cava was demonstrated. An aortoiliac bypass was performed successfully, and the patient had had a good clinical recovery at long-term follow-up. PMID- 2916773 TI - Effect of hypothermia on the pharmacokinetics of ethanol in piglets. AB - The effect of hypothermia (29 C) on the pharmacokinetics of ethanol was studied in eight piglets serving as their own normothermic controls. Ten milliliters of 12% ethanol per kilogram were infused over 30 minutes, and serum ethanol concentrations were measured for seven hours. Ethanol concentration data were fitted to one-compartment open model assuming Michaelis Menten elimination kinetics. During hypothermia, ethanol concentrations were consistently higher than during normothermia. This observation could be explained by both a significantly smaller distribution volume of ethanol during hypothermia (0.71 +/- 0.03 L/kg at 29 C and 0.84 +/- 0.05 L/kg at 37 C, P less than .02) and a significantly slower maximum velocity of metabolism of ethanol (Vm) during hypothermia (1.12 +/- 0.11 mg/kg.min vs. 1.83 +/- 0.21 mg/kg.min, P less than .01). Our study indicates that during hypothermia, ethanol stays significantly longer in the circulation in piglets. Potentially, this may contribute to a more profound effect from the ethanol. PMID- 2916774 TI - Early versus late fluid resuscitation: lack of effect in porcine hemorrhagic shock. AB - The benefit of IV fluid therapy in the prehospital management of hemorrhagic shock is unproven. We used a reproducible, lightly anesthetized model of porcine continuous hemorrhage to evaluate the usefulness of pre-hospital IV fluid therapy. Incorporated into the model were time delays associated with ambulance request and dispatch, patient evaluation and treatment, and transport to the hospital in the average urban prehospital care system. Treatment occurred concurrently with hemorrhage. Twenty-eight immature swine (15 to 20 kg) were bled at a rate of 1.25 mL/kg/min. Animals in the prehospital IV group (n = 14) received fluid resuscitation at 1 mL/kg/min beginning 20 minutes after initiation of hemorrhage; those in the in-hospital IV group (n = 14) received fluid at a rate of 3 mL/kg/min beginning 35 minutes after hemorrhage. Both groups received blood and saline at 3 mL/kg/min 45 minutes after hemorrhage began, and both groups had hemorrhage controlled 25 minutes after simulated hospital arrival. Survival was 57% in both groups, and there were no statistically significant differences seen in measured hemodynamic or biochemical parameters. We conclude that early administration of IV normal saline has no effect on hemodynamics or survival in this porcine hemorrhagic shock model simulating an urban prehospital care system. PMID- 2916775 TI - Transtracheal needle catheter ventilation in complete airway obstruction: an animal model. AB - Transtracheal needle catheter ventilation (TNCV) may be used as an alternative airway when contraindications to endotracheal intubation exist. A feline model tested the efficacy of low-flow oxygen delivery, and initial data were gathered to define proper catheter calibers to effect adequate oxygenation and ventilation. Cats were anesthetized, trachea intubated, and ventilated for 30 minutes with a pressure-regulated ventilator. Arterial and venous pressures were monitored, and a chest tube was inserted to measure intrathoracic pressures. Arterial blood gas analysis was performed every five minutes during the baseline period. The endotracheal tube was then removed, the trachea cross-clamped, and TNCV instituted. Oxygen flow rates of 1, 3, and 5 L/min were varied with catheter sizes of 14, 16, and 18 g. Data demonstrated that TNCV provided adequate oxygenation and ventilation with flow rates of 3 and 5 L/min with the 14- and 16 g catheters. Satisfactory oxygenation could be obtained with these flow rates with the 18-g catheter, but ventilation was inadequate. Ventilation was unsatisfactory with the 1 L/min flow rate in all catheter sizes. These preliminary data indicate that a minimum catheter:trachea cross-sectional area ratio of 0.03 may be required to obtain oxygenation and ventilation with low-flow oxygen rates of 3 to 5 L/min in cats. PMID- 2916776 TI - Modeling emergency department operations using advanced computer simulation systems. AB - We developed a computer simulation model of emergency department operations using simulation software. This model uses multiple levels of preemptive patient priority; assigns each patient to an individual nurse and physician; incorporates all standard tests, procedures, and consultations; and allows patient service processes to proceed simultaneously, sequentially, repetitively, or a combination of these. Selected input data, including the number of physicians, nurses, and treatment beds, and the blood test turnaround time, then were varied systematically to determine their simulated effect on patient throughput time, selected queue sizes, and rates of resource utilization. Patient throughput time varied directly with laboratory service times and inversely with the number of physician or nurse servers. Resource utilization rates varied inversely with resource availability, and patient waiting time and patient throughput time varied indirectly with the level of patient acuity. The simulation can be animated on a computer monitor, showing simulated patients, specimens, and staff members moving throughout the ED. Computer simulation is a potentially useful tool that can help predict the results of changes in the ED system without actually altering it and may have implications for planning, optimizing resources, and improving the efficiency and quality of care. PMID- 2916777 TI - Computerized algorithm-directed triage in the emergency department. AB - A retrospective audit was conducted evaluating the effectiveness of the computerized algorithm-directed triage at Brooke Army Medical Center. A total of 98,086 charts were reviewed. From this, 58,282 patients were given dispositions to our acute care clinic and the remainder to the emergency department. Of these, 733 patients (1.2%) were retriaged from the acute care clinic to the ED. Based on these data, we conclude that the computerized algorithm-directed triage, using minimally trained personnel, appears to be an effective system. PMID- 2916778 TI - Targeted recruitment of senior citizens and cardiac patients to a mass CPR training course. AB - CPR courses attract a predominance of young, healthy adults. Targeted recruitment of senior citizens and family members of cardiac patients has been suggested but inadequately studied. We used a targeted recruitment strategy for our annual mass CPR training course to determine if such an approach would be effective in attracting the target group. Targeting significantly increased the percentage of senior citizen participants and participants who took the course because they or a close friend or relative had cardiac disease (P less than .00001). These data have important implications regarding potential future CPR training course recruitment methods compared with nontargeted recruitment approaches. PMID- 2916779 TI - Emergency medical care requirements for large public assemblies and a new strategy for managing cardiac arrest in this setting. AB - During the 1986 World's Exposition held in Vancouver, British Columbia, the types and frequencies of emergency medical problems were assessed. The average number of patients seeking care was 3.93 +/- 0.95 per 1,000 visitors (daily range, 1.94 to 6.8). Patient loads were linearly related to gate attendance, but the correlation was imperfect (P less than .001, r = .63). Only 4.4% of patients evaluated on site by nurses and paramedics were referred for additional testing and treatment: of these patients, 30% had suspected serious musculoskeletal injury, 16% had abdominal pain, and 25% had complaints of chest pain, dizziness, or loss of consciousness. Lay employees (security personnel) were trained to use automatic external defibrillators. There were six cardiac arrests (0.3 per million visitors). Two patients collapsed with ventricular fibrillation, were defibrillated by lay personnel, quickly regained consciousness, and survived. The other arrests were associated with asystole or electromechanical dissociation; no shocks were inappropriately given, and all four died. We conclude that four of every 1,000 persons at this assembly sought emergency medical care, that 95% of the problems seen were minor with few requiring physician skills, and that the automatic external defibrillator was suited for this setting and could be used by lay responders to provide early definitive treatment. PMID- 2916780 TI - Vertical trauma: injuries to patients who fall and land on their feet. AB - We reviewed the patterns of injuries sustained by 12 consecutive fallers and jumpers in whom primary impact was onto the feet. The fall heights ranged from 20 to 100 ft. The 12 patients sustained 49 significant injuries. Skeletal injuries were most frequent and included 15 lower extremity fractures, four pelvic fractures, and nine spinal fractures. In two patients, paraplegia resulted. Genitourinary tract injuries included bladder hematoma, renal artery transection, and renal contusion. Thoracic injuries included rib fractures, pneumothorax, and hemothorax. Secondary impact resulted in several craniofacial and upper extremity injuries. Chronic neurologic disability and prolonged morbidity were common. One patient died; the patient who fell 100 ft survived. After initial stabilization, survival is possible after falls or jumps from heights as great as 100 feet It is important to recognize the skeletal and internal organs at risk from high magnitude vertical forces. PMID- 2916781 TI - Urine sampling in ambulatory women: midstream clean-catch versus catheterization. AB - We conducted a study to determine if there were any significant differences in urinalyses or urine cultures obtained by midstream clean-catch (MSCC) urine sampling in comparison with in-and-out catheterization (CATH). One hundred five women with symptoms suggestive of a urinary tract infection were studied prospectively. Each woman had a MSCC urine sample obtained initially, followed by a CATH sample. The MSCC and CATH urine samples were analyzed and compared for urine culture, leukocyte esterase, nitrites, microscopic bacteriuria, and pyuria. Of the 105 patients, 42 (40%) had a culture-proven urinary tract infection. The concordance rates between MSCC and CATH urine cultures, nitrites, leukocyte esterase, significant microscopic bacteriuria, and pyuria were 96%, 94%, 93%, 90%, and 90%, respectively. There were no statistically significant differences between MSCC and CATH sensitivities, specificities, or positive or negative predictive values for any urinalysis variable (leukocyte esterase, nitrites, significant microscopic bacteriuria, or pyuria). We conclude that if proper MSCC technique is used, the differences between MSCC and CATH urinalyses or urine cultures do not appear to be significant in the majority of ambulatory women without active vaginal bleeding who present with symptoms suggestive of a urinary tract infection. PMID- 2916782 TI - Thermal stability of prehospital medications. AB - To evaluate the effect of prolonged environmental extremes on common prehospital medications, four identical sets of 23 drugs were placed in a simulated environment for up to four weeks. Subsequently, the samples were analyzed by gas chromatography-mass spectrometry for evidence of degradation byproducts. Twenty one of the 23 samples showed no breakdown products; however, isoproterenol demonstrated 11% loss of parent compound after four weeks of environmental exposure. Epinephrine manifested a change in its ionized state after exposure to heat; the physiologic effect of this change was not determined. Our results suggest that rural and suburban emergency medical services providers, whose medications may not be replaced until they are used in patient care, must monitor their drug boxes' duration of exposure to uncontrolled conditions. PMID- 2916783 TI - Nitrous oxide analgesia in a pediatric emergency department. AB - Nitrous oxide (N2O) has been shown to be an effective analgesic in adult medical outpatients, yet no prospective studies of its use in the pediatric medical outpatient exist. Thirty-four children requiring laceration repair were randomly assigned to one of two treatment groups: 30% N2O/70% O2 or a placebo, 100% O2. Pain behavior, using the observer-scored Children's Hospital of Eastern Ontario Pain Scale, was assessed by double-blind techniques, before and during the laceration repair. Less pain behavior was seen in children less than 8 years old who received the N2O mixture than in those receiving the placebo. In patients 8 or more years old who received N2O, there was a significant improvement in the second evaluation as compared with those receiving only O2 during the procedure (P less than .05). There also was a smaller increase in pain behavior, from the first to the second evaluation, in those receiving N2O (P less than .05). No side effects were encountered. The authors conclude that continuous N2O inhalation is an effective and painless analgesic in children for outpatient procedures. More effective analgesia will likely occur with 40% to 50% N2O, although these concentrations remain to be studied in pediatric outpatients. PMID- 2916784 TI - Emergency department presentation of cocaine intoxication. AB - All patients who presented to the emergency department as a result of cocaine intoxication during a one-year period were reviewed retrospectively. One hundred thirty-seven cases were reviewed. Patients presented with a wide variety of chief complaints including altered mental status (40%), chest pain (21%), syncope (19%), suicide attempt (13%), palpitations (12%), and seizures (12%), as well as numerous other complaints. There was only one death. Few patients required treatment within the ED; sixteen required hospitalization. PMID- 2916785 TI - Dead Sea water poisoning. AB - A unique chemical intoxication by Dead Sea water and its resultant physiological effects of combined severe hypercalcemia and hypermagnesemia are described. Of 48 adult patients, 16 had at least one severe clinical manifestation of either disturbed sensorium or a syndrome similar to adult respiratory distress syndrome. The patients had tachyarrhythmias (11 of 38, 29%), conduction disturbance (nine of 37, 24%), and a normal QTc interval in the presence of severe hypercalcemia. Combined respiratory and metabolic acidosis and concomitant extreme hypercalcemia and hypermagnesemia, reaching serum levels up to 28.8 and 33 mg/dL, respectively, were responsible for most of the clinical findings. The adult mortality was 19%. Four pediatric patients with variable degrees of intoxication survived. Discriminant function analysis determined that admission serum calcium concentration of more than 15.5 mg/dL was the best predictor of mortality. In patients with severe intoxication, supportive medical treatment, including forced diuresis, was disappointing. Early dialysis for severe cases merits further study. PMID- 2916786 TI - Intravenous magnesium sulfate in the management of acute respiratory failure complicating asthma. AB - IV magnesium sulfate was administered to a 72-year-old man with acute respiratory failure secondary to a severe asthma attack. The patient had clinically deteriorated despite aggressive standard treatment and evidenced acidosis and hypercarbia by arterial blood gas determination. An IV dose of 1 g MgSO4 produced rapid clinical and arterial blood gas improvement and enabled management of the patient without endotracheal intubation and mechanical ventilation. This is the first reported case of the use of IV MgSO4 to prevent intubation and assisted ventilation in a patient with acute respiratory failure complicating asthma. PMID- 2916788 TI - Dorsal dislocation of four metacarpophalangeal joints. AB - We report the case of a 23-year-old man who fell from a third-floor window and injured his left hand. Physical examination and radiographic evaluation revealed open dorsal metacarpophalangeal dislocation of four fingers. The index finger dislocation was reduced in the emergency department, and the other three fingers responded to closed reduction during surgery. The patient made an uneventful recovery without complications. Metacarpophalangeal dislocations are unusual, with multiple dislocations rarely described. PMID- 2916787 TI - Hypermagnesemia associated with catharsis in a salicylate-intoxicated patient with anorexia nervosa. AB - While clinicians have raised concerns about giving multiple doses of a cathartic as a part of therapy for acute poisoning, fears of excessive magnesium absorption or fluid or electrolyte imbalances have been largely unrealized. We present the case of a 19-year-old woman with anorexia nervosa and long-term laxative abuse who, despite a normal baseline serum magnesium concentration, developed hypermagnesemia during treatment with multiple doses of activated charcoal magnesium citrate for acute salicylate intoxication. The peak serum magnesium concentration, after two doses of magnesium citrate, reached 9.8 mg/dL (4.0 mmol/L). It fell to normal levels when sorbitol was substituted as a cathartic and after the patient had been hemodialyzed for symptoms of salicylate toxicity that continued despite conventional therapy. While disordered magnesium metabolism in one patient with a severe underlying medical condition should not interdict the use of repetitive doses of magnesium citrate as a cathartic, patients requiring such therapy should have serum magnesium concentrations measured serially to monitor for signs of magnesium loading. PMID- 2916789 TI - Catfish stings: a report of three cases. AB - During a two-month period, three patients with embedded freshwater catfish spines were seen. In each case, the spine was visualized radiographically and then removed. All three patients completed a course of cephalosporins and recovered without infection. PMID- 2916790 TI - Military emergency medical systems. PMID- 2916791 TI - Limitations of magnesium levels study. PMID- 2916792 TI - Digisorb--instrument, not a drug. PMID- 2916793 TI - Telling the living--Part 2. PMID- 2916794 TI - Managing cocaine crisis. PMID- 2916795 TI - Problems with R2 pads. PMID- 2916796 TI - Cardiac ultrasound in the ED. PMID- 2916797 TI - Detection of early gastric cancer in an aggressive endoscopy unit. AB - Early Gastric Cancer (EGC) is defined as tumor invasion limited to the mucosa and submucosa, irrespective of regional lymph node involvement. These patients have five-year survival rates in excess of 90 per cent. Although frequently seen in Japan, the detection of ECG remains uncommon in the United States. Twenty-two patients with EGC over a 15-year period were reviewed. EGC was identified in 0.5 per cent (1/207) of all gastric cancers before the widespread use of endoscopy (1972-1979) in our institution and in 16.5 per cent (21/127) of such patients after endoscopy began to replace barium contrast studies (1980-1987). Radiographic studies were performed initially in 14 out of 22 patients with EGC, and in ten patients were reported as normal. Endoscopy was used to make the diagnosis of EGC in 21 of 22 patients. Nineteen of the 22 patients are currently alive and free of disease (86%) with a mean follow-up of 3.4 years (range 6 months to 12 years). Our experience has paralleled that of the Japanese in that, with the adoption of fiberoptic endoscopy as the first-line diagnostic modality in patients with GI complaints, the detection of EGC has significantly increased. PMID- 2916798 TI - Balloon dilatation of gastro-gastrostomy strictures in gastroplasty revisions. AB - Several gastric operations have been developed for the control of morbid obesity. Further surgical intervention may be necessary because of failure to lose weight or complications associated with the previous operation such as intolerable reflux symptoms. Revision from a horizontal to a vertical staple line may result in a stenosis at the site of the gastro-gastrostomy. This study examines the authors' experience with balloon dilation of these strictures. Between May, 1981 and September, 1987, 12 of 113 patients who had revision of previous gastric reduction procedures developed either gastro-gastrostomy stenosis or stenosis above the Marlex collar (2 patients). Endoscopic balloon dilatation was attempted in all 12 patients. Eight females and four males (average age, 42 years) had undergone either a previous vertical banded gastroplasty (VBG) (2 patients), gastric bypass, or horizontal gastroplasty as their initial operation. Revision was performed for failure of the initial operation to control weight, obstructive symptoms, or gastroesophageal reflux. Balloon dilatation was possible in 11 of 12 patients. The majority required less than four dilations to alleviate obstructive symptoms. Balloon dilatation is effective in the management of gastro-gastrostomy stenosis following revision of gastric stapling procedures. PMID- 2916799 TI - Colonoscopic decompression for pseudo-obstruction of the colon. AB - The purpose of this report was to review the authors' experience with colonoscopy as a method of treating patients with acute colonic distention. For the period 1981-1987, 19 patients at two teaching hospitals met the selection criteria for this study. In terms of measurable decompression of a colon distention, colonoscopy was successful in 89 per cent of patients, although 41 per cent required repeat endoscopic decompression during their hospital stay. The procedure failed in two patients (11%) and operative decompression was necessary. The authors have found that colonoscopy is a useful procedure for determining the cause of progressive colon distention and for providing safe and effective treatment. PMID- 2916800 TI - A simplified technique for the extirpation of the gastric bubble using an endo overtube. AB - Since 1982, the medical literature as well as the lay press discussed an artificial bezoar, the gastric bubble, as an adjuvant in the treatment of morbid obesity. Approved by the FDA, the Garren-Edwards Gastric Bubble has been reported by the company to have been placed over 17,000 times. Due to a reported increased rate of deflation after three months, removal and reimplantation of a new bubble is recommended. After deflation, some difficulty in retrieval of the bubble has been reported. The authors report a new technique for bubble extraction. The bubble is visualized through a gastroscope and deflated using bicap cautery. The gastroscope is removed. The endo-overtube is placed on the gastroscope and this assembly is reintroduced through the esophagus to the level of the GE junction. The deflated bubble is visualized, grasped with a forceps, and withdrawn into the endo-overtube until becoming wedged. The entire assembly (gastroscope, overtube, forceps, and gastric bubble) are removed. With this technique, bubble removal has been simplified and has decreased the procedure length to approximately fifteen minutes. PMID- 2916801 TI - Colonoscopic extraction of foreign bodies from above the rectum. AB - There has been a considerable amount of experience with removal of rectal foreign bodies inserted transanally. Until recently removal of objects above the rectosigmoid junction has required laparotomy. A literature review reveals that since 1975 there have been 29 cases of colonoscopic removal of a variety of objects reported in fourteen publications. The authors have had experience with three cases of retained colonic foreign bodies (greater than 7 days) extracted using the colonoscope. All patients received preprocedure antibiotics and bowel preparation from below. All objects were removed using either the Olympus CF LB3R colonoscope or the Fujinon EVC-M videocolonoscope. The authors conclude that colonoscopic retrieval of foreign bodies is technically feasible, safe, less morbid, and less costly than laparotomy. This technique should be considered as the first step in management of these patients by endoscopic surgeons. PMID- 2916802 TI - The status of gastrointestinal endoscopy by surgeons in the Veterans Administration Healthcare System. A survey. AB - Between January and December 1987, a survey was sent to all Chiefs of Surgery in the Veterans Administration Healthcare System to assess current practices of surgical endoscopy. Results of this survey have shown a significant involvement in flexible gastrointestinal endoscopic procedures by most surgical services, especially those affiliated with major resident teaching programs. Total number of procedures performed, based on the projections of numbers of cases as reported, indicate that approximately 60,000 gastrointestinal endoscopic procedures are currently performed by surgeons each year in the Veterans Administration system in order to assess the greater than 90,000 gastrointestinal operations performed. Results of the survey also indicate that Chiefs of Surgery in the VA system enjoy a wide range of support by Gastrointestinal (GI) Medical Services in the VA, but generally this support is adequate. Part-time and full time surgeons in the VA need to increase overall Continuing Education activities in endoscopy as well as increase the number of surgeons affiliated with organizations interested in endoscopic care. PMID- 2916803 TI - Mid-infrared lasers for endoscopic surgery. A new class of surgical lasers. AB - Unlike the Nd:YAG, the CO2 laser produces well circumscribed tissue removal with little unwanted damage because of its high absorption coefficient relative to tissue water. Unfortunately, conventional quartz fibers cannot transmit wavelengths greater than three microns, well below the ten micron wavelength of the CO2 laser. Thus, fiberoptic transmission of CO2 laser requires use of exotic materials that lack the excellent properties of quartz fibers and that, in some cases, are toxic or chemically unstable. However, there are large peaks in the infrared absorption curve of water in the two to three micron region. Lasers that operate in this mid-infrared region should permit CO2-like precision of cutting, along with excellent transmission through quartz fiberoptics. Two mid-infrared lasers with a fiberoptic delivery system, the Er:YAG (2.94 micron) and the Tm-Ho Cr:YAG (2.15 micron) have been evaluated with human colon tissue in vitro and with rabbit gastric tissue in vivo. Histologic sections reveal excellently well localized lesions with minimal underlying thermal damage. Depth of penetration is controllable and occurs in very small increments. There is little spreading of the lesions at the 24 hour mark resulting from secondary thermal damage. Based on these facts, the authors think that these lasers will be of benefit to endoscopic surgeons. PMID- 2916804 TI - Percutaneous endoscopic gastrostomy. A mandate for complete diagnostic upper endoscopy. AB - One hundred patients underwent upper endoscopy for the placement of percutaneous endoscopic gastrostomies (PEGS) during a four year period from 1984 to 1988. These cases were retrospectively reviewed to document the need for total endoscopy during PEG. Ninety-seven per cent of the procedures were successful. In 89 per cent, a complete exam of the esophagus, stomach, and duodenum was performed, revealing pathologic findings in 59 per cent. The most common abnormalities were in the esophagus (23%) and the stomach (27%); however, a portion of the findings were also present in the duodenum (12%) and the pylorus (11%). Additional findings present in the complete esophagogastroduodenoscopy (EGD) done at the time of PEG included a five per cent incidence of gastric outlet obstruction and antral ulcers or polyps in six per cent. The breakdown of findings in the duodenum included eight per cent incidence of duodenal ulcers and four per cent incidence of duodenitis. A total of 22 per cent of the patients had some evidence of peptic ulcer disease. Many of the cases in which pathology was found required a change in medications and, when postoperative bleeding occurred after PEG, the other pathologic entity was much more likely to be the cause of the complication than the PEG. A careful and complete EGD is mandated every time a patient is scheduled for PEG. PMID- 2916805 TI - Postoperative percutaneous choledochoscopy. AB - Postoperative percutaneous choledochoscopy (PC) is becoming an important aid to surgeons in the diagnosis and treatment of complex biliary tract disease. The authors retrospectively examined the results of 27 PCs performed on 22 patients at the University of Louisville Affiliated Hospitals from 1980 to 1987. Indications for PC included: suspected choledocholithiasis stricture, sclerosing cholangitis, and cholangiocarcinoma. The biliary tree was accessed through a T tube tract in 18 patients, and through a biliary-enterocutaneous fistula in four patients. The patient population included 11 men and 11 women with a mean age of 62 years. T-tubes varied in size from #16F to #24F. The time allowed for T-tube tract maturation ranged from four weeks to five months. Percutaneous choledochoscopy was performed 16 times in 13 patients for possible choledocholithiasis. Stones were present in 13, and 11 of 13 attempted extractions were successful. Two patients underwent PC for stent placement. Nine procedures were performed on eight patients to obtain biopsies or to evaluate possible strictures. Four studies were normal, two patients had sclerosing cholangitis, one had a stricture of the Sphincter of Oddi, and one patient had benign ductal tissue on biopsy after an iridium implantation for cholangiocarcinoma. Two minor complications occurred in this series. The authors conclude that by using PC the surgeon may safely manage complicated biliary problems and avoid re-operation in selected cases. PMID- 2916806 TI - Standard formats for electronic transfer of clinical data. PMID- 2916807 TI - Zidovudine for thrombocytopenic purpura related to human immunodeficiency virus (HIV) infection. AB - STUDY OBJECTIVE: To determine whether zidovudine is effective in increasing the platelet count in patients with thrombocytopenic purpura related to human immunodeficiency virus (HIV) infection. DESIGN: Nonrandomized controlled trial with two consecutive regimens. SETTING: Immunopathology and hematology clinics at two general hospitals. PATIENTS: Consecutive sample of 34 patients infected with HIV who had thrombocytopenic purpura (platelets less than 50 x 10(9)/L) without visceral bleeding. Twenty-nine patients completed the study; one patient was removed because of drug toxicity. INTERVENTIONS: Zidovudine for 12 weeks, 250 mg every 6 hours orally in 10 patients; and 500 mg every 8 hours orally in 24 patients. MEASUREMENTS AND MAIN RESULTS: Three of ten patients receiving 250 mg every 6 hours and 12 of 24 patients receiving 500 mg every 8 hours had a persistent increase in their platelet counts. In both groups the mean value of the platelet count increased significantly by week 12; from 28 x 10(9)/L +/- 12 (SD) to 57 x 10(9)/L +/- 36 in the first group and from 20 x 10(9)/L +/- 13 to 77 x 10(9)/L +/- 42 in the second group (P less than 0.05 and P less than 0.01, respectively). CONCLUSIONS: Zidovudine is effective on platelet counts in some patients with HIV-related thrombocytopenia. These results suggest that HIV itself may play a direct or indirect role in the pathogenesis of this disorder. PMID- 2916808 TI - Childhood cancer survivors' knowledge of their diagnosis and treatment. AB - PURPOSE: To determine what factors correlated with the failure of the survivors of childhood cancer to acknowledge their diagnosis. STUDY DESIGN: A follow-up interview with 1928 adults who survived childhood cancer to evaluate the late effects of cancer and its treatment. Cancer was diagnosed in these survivors between 1945 and 1974 before they reached age 20: subjects had to have survived for at least 5 years and to have reached age 21. RESULTS: Fourteen percent of the survivors of malignancies at sites other than the central nervous system said that they had not had cancer. This proportion differed according to the survivors' race, the type of tumor and its treatment, the level of their father's education, the year of diagnosis, and the center where the tumor was diagnosed. Among survivors who knew that they had cancer previously, however, most (81%) correctly identified the type of treatment they had received. CONCLUSIONS: Physicians should be aware that a substantial proportion of long-term survivors of childhood cancer may not reveal their past history of cancer and its treatment, and possible clues to the cause of the presenting condition may thus be missed. PMID- 2916809 TI - Pyuria and asymptomatic bacteriuria in elderly ambulatory women. PMID- 2916810 TI - Hypokalemic periodic paralysis due to the Sjogren syndrome in Chinese patients. PMID- 2916811 TI - The chronic fatigue syndrome. PMID- 2916812 TI - Aerosolized pentamidine. PMID- 2916813 TI - Magnetic resonance scanning in the Sjogren syndrome. PMID- 2916814 TI - Testicular cancer, clinical stage I. PMID- 2916815 TI - Excessive drug challenge. PMID- 2916816 TI - Lovastatin and visual changes. PMID- 2916817 TI - Wide QRS-complex tachycardia. PMID- 2916818 TI - Doctor, patient, and family. PMID- 2916819 TI - Ethical decisions in small hospitals. PMID- 2916820 TI - Laser surgery for vocal cord carcinoma involving the anterior commissure. AB - Endoscopic laser surgery is an established means of treatment for benign laryngeal lesions. Laser surgery for early (stages I and II) squamous cell carcinoma is still being tested. Treatment of glottic tumors extending to the anterior commissure is in itself controversial. Approximately 20% of all glottic tumors involve the anterior commissure, with only 1% of these lesions being purely anterior commissure tumors. The anatomy of the anterior commissure is such that an apparent T1 lesion may actually be a T4 lesion if it involves the thyroid cartilage. The distance between the anterior commissure ligament and the thyroid cartilage is only 2 to 3 mm. A preoperative computed tomographic scan can aid us in evaluating this space. Therefore, tumors of the anterior commissure present as a therapeutic challenge. Radiation therapy has proven to be inadequate, with a high rate of recurrence and increased risk for radiochondronecrosis. The literature with regard to radiotherapy varies widely as to survival rates. Conservation surgery has consistently demonstrated an 80% survival in T1 lesions. Recently, it has been suggested that laser surgery in the region of the anterior commissure might offer satisfactory results. We have found the opposite. We will report on five patients who underwent endoscopic laser surgery on T1 vocal cord lesions involving the anterior commissure. All of these patients had tumor recurrence and subsequently have undergone salvage surgery and/or radiation therapy. The difficulties associated with endoscopic laser surgery of the anterior commissure will be discussed with a supporting animal study. PMID- 2916821 TI - Choanal atresia: treatment trends in 47 patients over 33 years. AB - From 1977 through 1985, 11 patients underwent surgical correction of choanal atresia. This group brings the total number of patients corrected at our institution since 1951 to 47. This review compares treatment and outcome in the most recent group with the previous series of 36 patients. Eight patients were female and three were male; their ages at the time of surgical treatment ranged from 1 day to 19 years. The atresia was bilateral in five patients and unilateral in six. Six patients had other physical or mental developmental problems. Mean follow-up was 5.6 years (range, 2 to 10 years). All five patients who had transnasal puncture as primary treatment required reoperation; this is a higher incidence of failure than in the previous group. None of the three patients who had transpalatal procedures needed further operation. In two of the eight patients who had transseptal repair, restenosis developed. PMID- 2916822 TI - Effects of cricothyroid muscle contraction on laryngeal resistance and glottic area. AB - To determine the functional significance of the cricothyroid muscle (CT) in respiration, laryngeal resistance was measured in anesthetized dogs, along with electromyographic activity of the posterior cricoarytenoid muscle (PCA) and CT. In two dogs the larynx was videotaped simultaneously via a telescope. Increased CT activity was induced by airway occlusion or hypercapnia. Observations were carried out before and during cold blockade of the recurrent laryngeal nerve (RLN) or the nerve to the CT (external branch of the superior laryngeal nerve [Ext SLN]). Paralysis of the CT had no effect on laryngeal resistance or glottic area, even at very high levels of CT activity. Blockade of the RLN increased inspiratory resistance, but did not have a significant effect on expiratory resistance. Electrical stimulation of the Ext SLN produced tetanic CT contraction, which increased laryngeal resistance in both inspiration and expiration. This was true even at very high levels of PCA activity. These results indicate that although artificially induced CT contraction markedly affects laryngeal resistance, physiologic levels of respiratory activity do not have a significant effect. PMID- 2916823 TI - Partial laryngectomy and radiotherapy for supraglottic cancer: a conservative approach. AB - This is a retrospective study of 33 patients with supraglottic cancer treated with partial laryngectomy and moderate-dose radiotherapy at the University of Virginia from 1967 through 1986. All patients had a 2-year minimum follow-up. Ten patients received preoperative radiotherapy, and 23, postoperative radiotherapy. The 2-year adjusted survival rate was impressive at 97%. Local control at 2 years was 96%, including one patient who was salvaged with total laryngectomy. Control of the neck was 90% at 2 years. Ninety percent of the patients alive at 2 years had a functional voice. One patient required a completion laryngectomy for chronic aspiration. Conservation surgery with radiotherapy provides excellent survival as well as locoregional control rates with preservation of function in selected patients with supraglottic cancer. This approach may be especially helpful in the management of bulky T2 lesions as well as T4 lesions with minimal vallecula or base of tongue involvement. PMID- 2916824 TI - Asymmetry of the laryngeal framework: a morphologic study of cadaver larynges. AB - Asymmetry of the laryngeal framework was investigated with 50 excised human larynges, ten from newborns (five males, five females), 20 from adults in their 20s (ten males, ten females), and 20 from adults in their 50s (ten males, ten females). All adults were right-handed. The results are summarized as follows. 1) The laryngeal framework was asymmetric to a greater or lesser extent in all larynges. 2) The degree of asymmetry did not differ among different age groups or between sexes. 3) In newborns, there was no directional preponderance in asymmetry. 4) In older adults, there was a directional preponderance in asymmetry. The right thyroid lamina tended to tilt laterally whereas the left lamina showed a tendency to tilt medially. The right cricoarytenoid joint tended to be located slightly more laterally, posteriorly, and inferiorly than the left joint. The longitudinal axis of the thyroid cartilage was inclined to shift to the right posteriorly against the axis of the cricoid cartilage. The thyroid cartilage as a whole tended to tilt to the right against the cricoid cartilage. 5) There must be some compensatory mechanisms for the asymmetric framework to keep the vocal fold edges relatively symmetric. PMID- 2916825 TI - Sectional anatomy of the larynx: implications for the transcutaneous approach to endolaryngeal structures. AB - A transcutaneous, transcricothyroid membrane approach to endolaryngeal structures is used for several techniques such as placement of electrodes for laryngeal electromyography and transcutaneous Teflon injection of the paralyzed vocal fold. The purpose of this study is to examine the sectional anatomy of the larynx with respect to the cricothyroid membrane and describe a suitable transcutaneous approach to endolaryngeal structures. Sixteen whole organ cadaveric larynges were frozen in clear gelatin to facilitate sectioning. Specimens were sectioned in the transaxial, sagittal, and coronal planes as well as 30 degrees, 45 degrees, and 60 degrees from the transaxial plane. For clinical orientation, the transaxial plane was defined as 90 degrees from the most anterior plane of the cricothyroid membrane. Sections were examined and angles and depths of penetration were measured with respect to the transcutaneous approach to endolaryngeal structures. PMID- 2916826 TI - Current and future horizons in laryngeal and voice research. AB - Voice dysfunction is associated with neuromuscular impairment of laryngeal control and is often difficult to diagnose by indirect examination of the larynx. The newer techniques, currently used in the UCLA-Veterans Administration Medical Center Laboratories, provide some methods that aid in the diagnosis of voice impairment by providing documented objective data. Illustrative case reports of disorders of neuromuscular dysfunction of the larynx are presented and future research needs and direction are discussed. PMID- 2916827 TI - Contractile properties of canine thyroarytenoid muscle reinnervated from the ansa cervicalis. AB - In an attempt to obtain data on the contractile properties of vocal fold muscle reinnervated from the ansa cervicalis, we severed the recurrent nerve and connected its distal stump to the ansa cervicalis by an end-to-end anastomosis in a series of dogs. Each dog was allowed to heal for 5 months. Then the section of the thyroid cartilage on which the vocal fold muscle inserted was detached, connected to an isometric force transducer, and activated by indirect stimulation successively on both the operated and unoperated sides. A series of twitch contractions was recorded from each side. In two dogs no contractile response was obtained. In the three others, the twitch contraction time was increased significantly, by 23% to 60%. In two of three dogs, the operated muscle was significantly weaker than the unoperated muscle. The reinnervated thyroarytenoid muscle changed its speed in the direction of the donor sternothyroid muscle. PMID- 2916828 TI - Model of a new generation of tracheostomy and endotracheal tubes. A preliminary study of sensors to monitor obstruction. AB - The feasibility of monitoring cannula obstruction was studied by conversion of the electrical resistance of substances that are capable of causing obstruction into audible auditory signals. Copper-nickel-gold electrodes were thermal pressed onto polyimide-based flexible films placed as 1-mm wide strips along the inner surface of tracheostomy and endotracheal tubes. The responses were fed into a resistance-to-frequency converter (IC 555 timer), and the output was frequency selected to generate auditory responses through a piezoelectric beeper. Quantitative estimates of responses from the IC output were computer averaged. Instantaneous obstruction detection was made possible by the immediate responsiveness of the device in the presence of obstruction. PMID- 2916829 TI - Facial nerve hemangioma. PMID- 2916830 TI - Laryngeal synkinesis: its significance to the laryngologist. AB - Basic research and surgical cases have shown that the injured recurrent laryngeal nerve (RLN) may regenerate axons to the larynx that inappropriately innervate both vocal cord adductors and abductors. Innervation of vocal cord adductor muscles by those axons that depolarize during inspiration is particularly devastating to laryngeal function, since it produces medial vocal cord movement during inspiration. Many patients thought to have clinical bilateral vocal cord paralysis can be found to have synkinesis on at least one side. This will make the glottic airway smaller, particularly during inspiration, than would true paralysis of all the intrinsic laryngeal muscles. Patients with bilateral vocal cord paralysis should undergo laryngeal electromyography. If inspiratory innervation of the adductor muscles is present, simple reinnervation of the posterior cricoarytenoid muscle will fail. The adductor muscles also must be denervated by transection of the adductor division of the regenerated RLN. PMID- 2916831 TI - Botulinum toxin injection for the treatment of oromandibular dystonia. AB - Dystonia is a neurologic disorder characterized by abnormal, involuntary movements causing twisting and turning postures; it is postulated to be a disorder of central motor processing. The dystonias, when classified by region of the body involved, have been characterized as focal, segmental, and generalized. Focal dystonia can affect jaw mechanics, leading to forceful contraction of the jaw muscles and resulting in inappropriate deviation of the jaw. Localized injections of botulinum toxin have been used successfully in the management of other focal or segmental dystonias. We have treated 20 oromandibular dystonia patients with botulinum toxin. Six patients had only jaw and tongue involvement; 11 had blepharospasm and jaw involvement; and three had jaw involvement as part of a more generalized dystonia. Five patients had been diagnosed originally and treated as having temporomandibular joint syndrome. All but one of the patients had improvement of their symptoms with the toxin injections. The patients averaged 47% improvement with the injections. PMID- 2916832 TI - Acute management of laryngeal trauma. Update. AB - The management of 120 laryngeal injury patients at a major trauma center over 23 years is presented in the form of two patient populations. The first population consists of 52 previously analyzed and reported laryngeal trauma patients who served as the basis for the subsequent refinement of treatment of a second population of 68 patients. Collectively, these patients form a series unique in that 1) it comprises the largest number of such injuries treated at one institution, 2) the management principles remained the same throughout the entire 23 years, and 3) the majority of the patients were managed by one physician. The experience gained from these patients is examined in the hope of resolving prevailing controversies about the treatment of the acutely injured larynx. PMID- 2916833 TI - Expression of monoclonal antibody-defined tumor markers in four carcinomas. AB - The specificity of monoclonal antibody-based, CA 125, CA 15-3, CA 19-9 and carcinoembryonic antigen (CEA) immunoassays were evaluated by studying how these tumor markers are expressed, using serial serum specimens from patients with breast, ovarian, colorectal, and pancreatic carcinomas. It was found that none of the monoclonal defined markers was specific for any single malignant disease. Multiple markers of increased concentration were found in all serial specimens. However, only one dominant marker was associated with each type of malignant disease. Taking advantage of the different patterns of these tumor markers expressed among different carcinomas, it was demonstrated that the specificity of these monoclonal immunoassays for diagnosis and screening of cancers could be improved if ratios of the dominant marker to other markers were determined. For example, determining ratios of CA 15-3/CEA, CA 15-3/CA 125, and CA 15-3/CA 19-9 will improve the differentiation of elevated CA 15-3 of breast carcinoma from those of colon, ovarian, and pancreatic carcinomas, respectively. PMID- 2916834 TI - Molecular cloning and analysis of full-length cDNAs cognate to a rat gene under multihormonal control. AB - Gene 33 is a multihormonally regulated rat gene whose transcription is rapidly and markedly enhanced by glucocorticoids, insulin, or cAMP. A cDNA clone (p216) containing a nearly full-length DNA complementary to the mRNA of this gene was isolated from a cDNA library and sequenced. The cDNA represents the entire mRNA transcript, except for three bases at the 5' terminus. The message is 2970 nucleotides long and can encode a protein of 459 amino acids with a molecular mass of 49,919 Da. The deduced amino acid sequence is rich in proline and serine but bears little homology to any known sequences. The 5' untranslated region, rich in G + C, is 270 nucleotides long and contains two apparently nonfunctional AUG initiator codons. The 3' untranslated sequence, rich in A + U, is 1323 nucleotides long and has a polyadenylation signal 13 bases upstream of the poly(A) tract. Two mRNA transcripts of the gene, which appear to be the consequence of alternative usage of splice sites, have been identified. The less abundant mRNA is truncated by 228 nucleotides in the protein coding region. The reading frame is maintained and this mRNA can code for a protein of 383 amino acids with a calculated molecular mass of 42,204 Da. PMID- 2916836 TI - Substrate specificity and inhibitors of a capillary injury-related protease from sheep lung lymph. AB - A serine protease (Mr 70,000 to 75,000) appearing in sheep lung lymph after capillary damage induced by Escherichia coli endotoxin, oleic acid, or air emboli, was studied for its specificity toward a series of synthetic peptide and thioester substrates containing an Arg residue in the P1 position. High specificity constants (kcat/Km) were generally obtained with substrates having two or more basic amino acid residues, and with those having a Gln residues in the P2 position. Secondary enzyme-substrate interactions at sites more removed from the scissile bond are of importance, since a few peptides with two basic residues were hydrolyzed slowly, and the site of cleavage of natural peptides was influenced by the amino acid sequence beyond the immediate vicinity of the hydrolyzed bond. The properties of the enzyme and its pattern of specificity distinguish it from enzymes of the clotting cascade, from components of the complement system, and from lung and skin tryptase. The enzyme was inactivated by p-amidinophenylmethanesulfonyl fluoride and by a series of mechanism-based isocoumarin derivatives, the most potent inhibitor being 4-chloro-7-guanidino-3 (2-phenylethoxy)isocoumarin. Enzyme solutions inactivated by reaction with isocoumarin inhibitors could be completely reactivated after 30 h by treatment with hydroxylamine at neutral pH. Formation of a stable sheep lymph acyl enzyme- in contrast to thrombin and other trypsin-like enzymes--is not followed by alkylation of an active site nucleophile that leads to irreversible enzyme inactivation. The high activity toward substrates with two basic residues suggests that the enzyme may potentially function in processing of precursors of bioactive peptides. PMID- 2916835 TI - Oxidation of aldehydic products of lipid peroxidation by rat liver microsomal aldehyde dehydrogenase. AB - Lipid peroxidation in microsomal membranes produces a large number of aldehydes, alcohols, and ketones, some of which have been shown to be cytotoxic. This study has determined the kinetic parameters for the oxidation of aldehyde lipid peroxidation products by purified rat hepatic microsomal aldehyde dehydrogenase (ALDH). Livers were obtained from male Sprague-Dawley rats for preparation of microsomal ALDH which was purified 400-fold. Kinetic parameters, Vmax and V/K, were determined for saturated and unsaturated aldehydes of three to nine carbons in length in the presence of NAD+. Of the aldehydes examined, only acrolein and 4 hydroxynonenal were not oxidized by ALDH. The Vmax values (mumol NADH produced/min/mg protein) increased linearly with carbon chain length and ranged from 6.5 to 23 for the saturated series and 4.0 to 9.0 for the unsaturated aldehydes. The affinity constant V/K (nmol NADH produced/min/mg protein/nmol aldehyde/liter) also increased with carbon chain length and ranged from 12 to 9000 for the saturated aldehydes and 13 to 5300 for the unsaturated aldehydes. These results suggest that microsomal ALDH may serve a biological role for detoxification of reactive aldehydes produced by lipid peroxidation of microsomal membranes. PMID- 2916837 TI - Sulfaquinoxaline inhibition of vitamin K epoxide and quinone reductase. AB - Sulfaquinoxaline (N1-(2-quinoxalinyl)sulfanilamide) has been shown to be a potent (Ki = 1 microM) freely reversible inhibitor of the dithiothreitol-dependent reduction of both vitamin K epoxide and vitamin K quinone by rat liver microsomes in vitro. This observation provides an explanation for the hemorrhagic syndrome occasionally seen in poultry on medicated feed and the efficacy of sulfaquinoxaline in anticoagulant based rodenticides. Sulfaquinoxaline inhibition resembled inhibition by coumarin anticoagulants (e.g., warfarin) and hydroxynaphthoquinones (e.g., lapachol). Inhibition was observed in assays using microsomes from control strain rats, but the enzyme was resistant to sulfaquinoxaline in microsomes from warfarin-resistant rats. Steady-state kinetics inhibition patterns were nearly competitive versus dithiothreitol and nearly uncompetitive versus vitamin K epoxide as is observed for warfarin and lapachol. These results suggest that this inhibitor binds to the oxidized form of vitamin K epoxide reductase in the same way as suggested for the coumarins and hydroxyquinones. Of 10 other sulfa drugs tested, none were inhibitors, and of fragments and related compounds tested, only 2-aminoquinoxaline benzenesulfonamide was active. These results provide a probably orientation in the binding site in relation to that for warfarin and lapachol. PMID- 2916838 TI - Actin filament capping and cleaving activity of cytochalasins B, D, E, and H. AB - The concentration dependences of the activities of cytochalasin B, D, E, and H in capping and cleaving actin filaments have been assayed using fluorescence photobleaching recovery. Filament capping was detected by the increase in mobile G-actin. Cytochalasin D (CD) showed the strongest filament capping activity, with an apparent dissociation constant from filament ends of 50 nM. The order of capping activity was CD greater than CH greater than CE much greater than CB. Filament cleavage was detected by the increase in the diffusion coefficients of actin filaments. By this criterion the order of filament cleavage activity was CD, CE greater than CH much greater than CB. Cytochalasin B shows some activity in cleavage of filaments over a concentration range (0-100 microM) at which it shows no appreciable capping activity. This activity, together with results from other groups, is interpreted to mean that CB binds to protomers within the filament, but not to the barbed end. The reversal of activities for CH and CE, combined with the activity profile of CB, constitute the strongest evidence to date that there is more than one cytochalasin binding site on the actin molecule. PMID- 2916839 TI - Pyruvate kinase isozymes from the green alga, Selenastrum minutum. I. Purification and physical and immunological characterization. AB - Pyruvate kinase from the green alga Selenastrum minutum consists of two isoforms (PK1 and PK2) separable by Q-Sepharose chromatography. The two isoforms have been highly purified to respective final specific activities of 42 and 23 (mumol pyruvate produced/min)/mg protein. Purification steps included salt fractionation, anion-exchange, hydrophobic interaction, and gel filtration chromatography. The final enzyme preparations differ significantly in physical and immunological properties. PK1 is heat labile and is completely inactivated following reaction with N-ethylmaleimide. In contrast, PK2 is heat-stable and is only partially inactivated following N-ethylmaleimide treatment. PK1 appears to be homotetrameric with a native molecular mass of about 240 kDa, whereas PK2 appears to be homodecameric with a native molecular mass of approximately 590 kDa. The antigenic reaction of both final PK preparations to rabbit antiserum prepared against homogeneous germinating castor bean endosperm cytosolic pyruvate kinase was tested by immunoprecipitation and Western blotting. The two algal pyruvate kinases are immunologically unrelated as only PK2 cross-reacts with the cytosolic pyruvate kinase antibodies. These data indicate that the S. minutum pyruvate kinase isoforms, PK1 and PK2, are not interconvertible forms of the same protein, but probably represent chloroplastic and cytosolic isozymes, respectively. PMID- 2916840 TI - Raman spectroscopic evidence for a disulfide bridge in calf gamma II crystallin. AB - Laser Raman spectroscopy has been applied to native and dithiothreitol-treated bovine cortical gamma II crystallin to examine the state of the thiol groups and the presence of a putative disulfide bridge. The data reveal significant differences in two key spectral regions. In the thiol stretching region (2500 2600 cm-1), the dithiothreitol-reduced form shows a 25% increase in the integrated Raman signal as compared to the native form. The magnitude of this increase corresponds to the presence of 1 mol of disulfide/mol of gamma II as determined both by the Raman data and the previous biochemical analysis from this laboratory. In the disulfide stretching region (500-540 cm-1), the native form shows a line near 511 cm-1 which is absent in the reduced form. Both native and reduced forms show a triple-banded thiol signal with one or more distinct shoulders, suggesting at least three and perhaps five different environments for the cysteine residues. The difference spectrum, obtained by a 1:1 computer subtraction of the native from the reduced form, indicates that the increase in thiol signal is centered around 2572 cm-1. In every other spectral region, both native and reduced gamma II forms are closely similar. These results strongly support the biochemical data reported earlier and indicate that the reduction of the single disulfide bridge is accompanied by minimal changes in secondary structure in solution. PMID- 2916841 TI - Prothymosin alpha and parathymosin: mRNA and polypeptide levels in rodent tissues. AB - Blot hybridization analyses have established the presence of mRNAs for prothymosin alpha (ProT alpha) and for parathymosin (ParaT) in rat and mouse lung, liver, kidney, and brain, confirming the biosynthesis of these peptides in nonlymphoid tissues. In these tissues the levels of mRNAs paralleled the content of the polypeptides, determined with specific radioimmunoassays. The mRNA levels also confirmed the reciprocal relation between the two polypeptides; ProT alpha and its mRNA were found in highest concentrations in spleen and thymus, followed by lung, kidney, and brain, with lowest concentrations in liver. On the other hand, liver contained highest concentrations of ParaT and the mRNA for ParaT, with lowest levels present in spleen and thymus. In comparison to tissues from young (6-8 week) mice, older (18 month) mice contained lower concentrations (20 40%) of both polypeptides, with qualitatively similar decreases in mRNA content. PMID- 2916842 TI - Disruption of rat hepatic microsomal electron transport chains by the selenium containing anti-inflammatory agent Ebselen. AB - The influence of Ebselen, an organoselenium anti-inflammatory agent, on the two electron transport chains present in rat liver microsomes has been studied. At low micromolar concentrations, Ebselen markedly inhibited the flow of reducing equivalents from NADPH-cytochrome P450 reductase to both its natural electron acceptor, cytochrome P450, and its artificial electron acceptor, cytochrome c. Similarly, the microsomal NADH-cytochrome c reductase system consisting of cytochrome b5 and its flavoprotein, NADH-cytochrome b5 reductase, was also significantly inhibited by Ebselen. The inhibition appears to be due to the inability of the reduced pyridine nucleotide to transfer electrons to the flavin (FAD and/or FMN) in the flavoprotein reductase. This was shown with the purified NADPH-cytochrome P450 reductase, which in the presence of Ebselen was not converted to the semiquinone form following the addition of NADPH. The addition of Ebselen to a suspension of hepatic microsomes from either untreated or phenobarbital-treated rats did not result in any spectral change characteristic of type I, type II, or reverse type I. PMID- 2916843 TI - Molecular cloning of salicylate hydroxylase genes from Pseudomonas cepacia and Pseudomonas putida. AB - The sal gene encoding Pseudomonas cepacia salicylate hydroxylase was cloned and the sal encoding Pseudomonas putida salicylate hydroxylase was subcloned into plasmid vector pRO2317 to generate recombinant plasmids pTK3 and pTK1, respectively. Both cloned genes were expressed in the host Pseudomonas aeruginosa PAO1. The parental strain can utilize catechol, a product of the salicylate hydroxylase-catalyzed reaction, but not salicylate as the sole carbon source for growth due to a natural deficiency of salicylate hydroxylase. The pTK1- or pTK3 transformed P. aeruginosa PAO1, however, can be grown on salicylate as the sole carbon source and exhibited activities for the cloned salicylate hydroxylase in crude cell lysates. In wild-type P. cepacia as well as in pTK1- or pTK3 transformed P. aeruginosa PAO1, the presence of glucose in addition to salicylate in media resulted in lower efficiencies of sal expression P. cepacia apparently can degrade salicylate via the meta cleavage pathway which, unlike the plasmid encoded pathway in P. putida, appears to be encoded on chromosome. As revealed by DNA cross hybridizations, the P. cepacia hsd and ht genes showed significant homology with the corresponding plasmid-borne genes of P. putida but the P. cepacia sal was not homologous to the P. putida sal. Furthermore, polyclonal antibodies developed against purified P. cepacia salicylate hydroxylase inactivated the cloned P. cepacia salicylate hydroxylase but not the cloned P. putida salicylate hydroxylase in P. aeruginosa PAO1. It appears that P. cepacia and P. putida salicylate hydroxylases, being structurally distinct, were probably derived through convergent evolution. PMID- 2916844 TI - Metabolism of retinol and retinoic acid by human liver cytochrome P450IIC8. AB - Liver microsomes obtained from nine subjects were found to metabolize retinol to polar metabolites, including 4-hydroxyretinol. In a reconstituted monooxygenase system containing human liver P450IIC8, retinol was converted to 4-hydroxyretinol and other polar metabolites, with a Km of 0.071 mM and a Vmax of 1.73 nmol/min/nmol P450. Neither P450IIC9 nor P450IIE1, two other purified human P450s, displayed significant retinol hydroxylase activity. Immunoblots performed with a monospecific antibody directed against human P450IIC8 revealed that appreciable amounts of this enzyme were present in human liver microsomes. The same antibody significantly inhibited retinol metabolism in liver microsomes and in the system reconstituted with P450IIC8. The system reconstituted with P450IIC8 also converted retinoic acid to polar metabolites. Thus, this study shows, for the first time, metabolism of two physiologic substrates by a human liver cytochrome P450 related to a group of "constitutive" rodent P450s believed to participate in the metabolism of endogenous compounds. Through its involvement in vitamin A metabolism, P450IIC8 may participate in maintaining the balance between those vitamin A concentrations that promote cellular integrity (and oppose the development of cancer) and those concentrations that cause cellular toxicity. PMID- 2916845 TI - Monoterpene biosynthesis: mechanism and stereochemistry of the enzymatic cyclization of geranyl pyrophosphate to (+)-cis- and (+)-trans-sabinene hydrate. AB - The conversion of geranyl pyrophosphate to (+)-cis- and (+)-trans-sabinene hydrate by a partially purified cyclase from sweet marjoram (Majorana hortensis) is considered to proceed by the initial ionization and isomerization of the substrate to (-)-(3R)-linalyl pyrophosphate and the subsequent cyclization of this enzyme-bound tertiary allylic intermediate to the monocyclic (+)-(4R)-alpha terpinyl cation. A 1,2-hydride shift and a second cyclization with water capture of the resulting cation complete the reaction sequence. [6-3H, 14C]Geranyl pyrophosphate, coupled with selective chemical degradation of the resulting sabinene hydrate products, was employed to demonstrate the hydride shift, while separate testing of the linalyl pyrophosphate enantiomers confirmed the involvement of the (3R)-antipode in the cyclization and indicated the cyclization of linalyl pyrophosphate to be faster than the coupled isomerization-cyclization of the geranyl substrate. (1R)- and (1S)-[1-3H, 14C]geranyl pyrophosphates, in conjunction with stereoselective degradations of the biosynthetic products to locate the 3H, were exploited to deduce that configuration at C1 of the substrate was retained in the reaction. These findings suggest the isomerization of the geranyl substrate to be a suprafacial process and the cyclization of the (3R) linalyl intermediate to proceed via the anti,endo-conformation consistent with the stereo-chemistry of other monoterpene cyclizations and with chemical model studies. Sulfonium ion analogs of the presumptive linalyl and alpha-terpinyl cationic intermediates of the isomerization-cyclization sequence were shown to be potent inhibitors of the enzymatic reaction (Ki = 0.3 and 2.8 microM, respectively), and inhibition was synergized by the presence of inorganic pyrophosphate, indicating that the enzyme recognized and bound more tightly to these ion-paired species than to either cationic or anionic partner alone. Additionally, the enzyme was capable of ionizing (solvolyzing) the noncyclizable substrate analogs 6,7-dihydrogeranyl pyrophosphate and 2,3-methanogeranyl pyrophosphate. These results define the overall stereochemistry of the coupled isomerization-cyclization to sabinene hydrate, demonstrate the 1,2-hydride shift, and confirm the electrophilic nature of this enzymatic reaction type. PMID- 2916846 TI - Molecular and immunologic differences in canine fibronectins from articular cartilage and plasma. AB - Two new monoclonal antibodies (Mabs) which reacted with canine fibronectin were produced and characterized. Data supported the conclusion that the epitope recognized by Mab 1H9A4 is within the first three Type III homology repeats of the Hep 2 domain and that the epitope for Mab 13G3B7 is within the last Type III homology repeat of fibronectin. These antibodies, along with three others, Mabs IST-2, IST-7, and IST-9, produced and characterized in the laboratories of L. Zardi of Genoa, Italy, were used to characterize canine cartilage and plasma fibronectin. In addition, cartilage explants were labeled with [35S]methionine in order to characterize newly synthesized cartilage fibronectin. The following observations were made. (i) Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (NaDodSO4-PAGE) of reduced canine plasma fibronectin revealed a characteristic doublet; reduced cartilage fibronectin revealed two major bands and one minor band. The lower molecular weight band was 10 kDa less than the beta subunit of plasma fibronectin. In Western blots, this band stained with Mab 1H9A4 but failed to react with Mab 13G3B7. (ii) Western blots of thermolysin and trypsin digests of cartilage fibronectin revealed cleavage patterns which differed from those obtained from digestions of plasma fibronectin. (iii) The ED A sequence, detected by Mab IST-9, was present in less than 2% of the cartilage fibronectins. (iv) NaDodSO4-PAGE of purified and reduced 35S-labeled fibronectin revealed two major radioactive bands and one minor radioactive band which comigrated with the fibronectin from the cartilage but not with plasma fibronectin. We concluded that like "cellular" fibronectin, the ratio of alpha type subunits to beta subunits was greater than 4 to 1 in cartilage fibronectin compared to 1.25 to 1 for plasma fibronectin; however, cartilage fibronectin was not a cellular fibronectin by the criterion of the presence of the ED-A sequence. Another difference between plasma and cartilage fibronectin was the presence in cartilage fibronectin of a subpopulation of subunits on which the last Type III homology repeat could not be detected. Biosynthetic data were consistent with the concept that cartilage fibronectin originates from local synthesis by the chondrocyte. PMID- 2916847 TI - Regulation of Chlorella nitrate reductase: control of enzyme activity and immunoreactive protein levels by ammonia. AB - Nitrate reductase catalyzes the initial step in the conversion of nitrate to organic nitrogen and is thought to be repressed by ammonia and induced by nitrate. Induction by nitrate and repression by ammonia were studied by following changes in NADH:nitrate reductase and the associated partial activities NADH:cytochrome c reductase and methylviologenr:nitrate reductase. Immunoreactive protein was assessed by enzyme-linked immunosorbent assay and immunoblotting. Molybdenum cofactor levels were investigated using the nit-1 complementation assay as well as fluorescence of the oxidized cofactor. The results indicate that the NADH:cytochrome c reductase activity is "induced" faster than the nitrate reducing activity and suggest that incorporation of the molybdo-pterin cofactor may be rate limiting in the expression of activity. Molybdenum cofactor levels are significantly elevated in nitrate-treated cells. Under "repressing" conditions all activities decreased at approximately the same rate. A more rapid conversion of the enzyme to a reversibly inactive form also occurred under these conditions. Changes in immunoreactive protein levels correlated most closely with NADH:cytochrome c reductase activity but appeared to increase faster during induction and decrease slightly slower during repression than the enzyme activities. Removal of exogenous ammonia results in the appearance of nitrate reducing activity, as well as immunoreactive protein (derepression). Studies using protein and RNA synthesis inhibitors indicated that de novo synthesis is required for nitrate reductase induction and were in agreement with the results of the immunoreactive studies. PMID- 2916848 TI - In vitro stimulation of rat liver retinyl ester hydrolase by ethanol. AB - Retinyl ester hydrolase (REH), the enzyme which converts retinyl esters to retinol, was partially characterized from whole liver homogenates of rats using an HPLC method with quantitation of retinol product. Optimal results were obtained by incubation of 1 mg of whole homogenate protein with 900 microM all trans-retinyl palmitate and 275 mM 3-[(3-cholamidopropyl)dimethylammonio]-1 propanesulfonate in a 0.1 M Tris-maleate buffer, pH 7.0, for 1 h at 37 degrees C. The enzyme assay proved to be sensitive and reproducible, with an interanimal coefficient of variation of 13% (n = 7). Because ethanol has been shown to mobilize vitamin A from the liver, we tested its effect on REH activity at several concentrations. In concentrations ranging from 0.01 to 0.5 M, ethanol added in vitro caused a concentration related increase in REH activity (from 20 to 86% above baseline activity). This increase was specific to ethanol as acetaldehyde, 1-propanol, and t-butanol either did not change or significantly decreased REH activity over the range of concentrations tested. The range of concentrations of ethanol causing stimulation in our assays was within the range of concentrations seen in the blood of rats after acute ethanol ingestion. Stimulation of REH activity could explain, in part, the well-known effects of ethanol on mobilization of vitamin A from liver stores. PMID- 2916849 TI - Identification of regulatory sites in the biosynthesis of ubiquinone in the perfused rat heart. AB - The biosynthesis of ubiquinone was studied in an isolated perfused beating heart preparation from adult male rats to determine rate-limiting steps in the biosynthetic pathway. The isolated heart could incorporate p-hydroxy[U 14C]benzoate into ubiquinones (ubiquinone-9 and -10) and two other lipids which were identified as 3-nonaprenyl 4-hydroxybenzoate and 3-decaprenyl 4 hydroxybenzoate. No other lipids could be detected. Addition of unlabeled mevalonolactone to the perfusate stimulated the rate of incorporation of p hydroxy[U-14C]benzoate into 3-nonaprenyl 4-hydroxybenzoate and 3-decaprenyl 4 hydroxybenzoate. The level of radioactivity in these intermediates was much greater than that in ubiquinone-9 and -10. These results show that in the intact heart there is a large excess capacity to form postmevalonate isoprenoid precursors of ubiquinone and suggest a possible regulatory step at the premevalonate level. Moreover, the accumulation of prenylated derivatives of 4 hydroxybenzoic acid indicates further rate limitation at one or more of the subsequent steps in conversion of these intermediates to ubiquinone. PMID- 2916850 TI - Glucocorticoid regulation of the rat cytochrome P450c (P450IA1) gene: receptor binding within intron I. AB - The actions of polycyclic aromatic hydrocarbons and glucocorticoids to regulate the expression of cytochrome P450c were investigated using cultured fetal rat hepatocytes. Cytochrome P450c mRNA content, determined by Northern blot analysis, was induced in cells treated with 1,2-benzanthracene from levels undetectable in untreated cells. When dexamethasone was included in the culture medium together with 1,2-benzanthracene there was a further 2-fold increase in the induction of cytochrome P450c mRNA. The concentration of dexamethasone required for a half maximal increase in cytochrome P450c mRNA content was approximately 10(-9) M. By nuclear run-on transcription assays, treatment with 1,2-benzanthracene induced cytochrome P450c transcription 5.3-fold over untreated cells. In the presence of dexamethasone and 1,2-benzanthracene, there was a further 2-fold increase in cytochrome P450c transcription. Southwestern blotting and exonuclease footprinting methods have identified binding interactions of a purified glucocorticoid receptor fraction with portions of the cytochrome P450c gene within the first intron. Using a chimeric plasmid containing the first intron, the first exon, and 824 bp of 5'-flanking region of the cytochrome P450c gene, chloramphenicol acetyltransferase activity was induced in transfected HepG2 hepatoma cells by the addition of 1,2-benzanthracene. The addition of dexamethasone induced a further 2.2-fold increase in activity. Deletion of the first intron within the chimeric plasmid abolished responsiveness to dexamethasone. It is concluded that glucocorticoids act together with polycyclic aromatic hydrocarbons to increase the levels of cytochrome P450c expressed in the fetal rat hepatocyte, and that this action is mediated by the glucocorticoid receptor. A glucocorticoid responsive element, which binds the glucocorticoid receptor, has been identified within the first intron of the cytochrome P450c gene. These results suggest that glucocorticoids play a significant role in the response of the hepatic cytochrome P450c gene to xenobiotics. PMID- 2916851 TI - Dietary intake of lead among Japanese farmers. AB - More than 1,000 24-h duplicates of food consumed were collected from farmers in 49 nonpolluted regions in Japan during the winter and summer seasons of 1977 1981. The samples were analyzed for lead to assess dietary intake. The dietary intake distributed log-normally in both winter and summer. The geometric mean (GM) (geometric standard deviation [GSD]) for winter samples was 38.2 micrograms/d (1.94) for males (N = 381) and 32.8 micrograms/d (1.91) for females (N = 711). A seasonal variation was detected in females but not in males. The findings on regional differences in dietary intake were inconclusive. The levels observed were lower than most values reported in the literature. The low dietary intake levels were in agreement with the low blood lead levels found among the subjects, which may reflect of Japan's decision in 1975 to withdraw alkyl lead from automobile gasoline. No significant correlation could be established between dietary intake and blood lead levels when GMs for the study regions were compared, or when dietary intake and blood lead levels were compared in 555 nonsmoking and nondrinking females who were between 30 and 59 y of age. It is estimated that 2-4 micrograms of lead is absorbed daily from the diet (i.e., food and water), and 0.1-1 micrograms is absorbed via respiration, and that cigarette smoking and alcohol consumption may increase lead absorption. PMID- 2916852 TI - Self-reported short- and long-term respiratory effects among PVC-exposed firefighters. AB - Firefighters exposed to burning polyvinyl chloride (PVC) were studied to assess respiratory effects at 5-6 wk post-incident and again 22 mo following the fire. Exposed subjects reported significantly more frequent and severe respiratory symptoms at both time points than did firefighter controls. In longitudinal analyses, a number of symptoms persisted over time, and acute symptom scores were significantly correlated with chronic scores. At Time 2, approximately 18% of exposed firefighters, compared with none of the controls, reported that since the time of the PVC exposure, a physician had told them that they had either asthma and/or bronchitis. PMID- 2916853 TI - Occupational illnesses from cholinesterase-inhibiting pesticides among agricultural applicators in California, 1982-1985. AB - California pesticide illness investigation reports involving toxicity category I or II organophosphate and carbamate pesticide exposures among agricultural pesticide applicators were reviewed for the years 1982-1985. The pesticides associated with each illness were recorded, and the exposures were classified as chronic, short-term, or accidental. Illnesses were associated with a range of pesticides, including both organophosphates and carbamates in both toxicity categories I and II. Approximately 19% of the illnesses were due to accidents. Overall, the analysis identified a need for improving occupational health surveillance and the regulations governing worker health and safety. PMID- 2916854 TI - Potential exposure levels and health effects of neighborhood exposure to a municipal incinerator bottom ash landfill. AB - An investigation was conducted to assess the potential exposure levels and pursuant public health implications of neighborhood exposure to a municipal incinerator bottom ash landfill. This site received ash from a single incinerator without pollution control devices from 1954-1973. Soil was sampled for 10 heavy metals, polychlorinated dibenzodioxins, polychlorinated dibenzofurans, 2,3,7,8 tetrachlorodioxin and furan congeners, polychlorinated biphenyls, and polycyclic aromatic hydrocarbons. Soil concentrations for these substances were converted to estimates of exposure, health effects, and/or cancer risk by the application of a general exposure model and exposure/effect and exposure/risk models for specific substances. The results of soil analysis and modeling indicate that the level of lead detected on the site was considerably above the recommended levels of the Centers for Disease Control (CDC) and may lead to an elevated blood lead level in exposed children above that currently defining a case of lead poisoning. The potential for health effects resulting from exposure to other substances measured in the soil on this site is considered to be small, and no significant increased cancer risk is expected. Comparison of levels of various substances obtained at this site with levels obtained in fresh bottom ash in other studies suggests that these results may be applicable to exposures from other municipal incinerator bottom ash landfills. PMID- 2916855 TI - Chromosome abnormalities and sister chromatid exchanges in children with acute intoxication due to inhalation of volatile substances. AB - Deliberate inhalation of volatile substances is a common and harmful practice among young persons worldwide. Recently, we described chromosome damage in children who chronically inhale volatile agents. Clinical and cytogenetic studies were performed for 15 "sniffing" children (13 boys and 2 girls), the purpose of which was to define the chromosomal effect of the acute intoxication. A significant increase in the rate of chromosome abnormalities and in the frequency of sister chromatid exchanges (SCEs) was found in sniffers vs. controls. The values were also higher in children who were acutely intoxicated than in those who chronically inhaled volatile agents. Clinical, socioeconomic, and cytogenetic findings are also discussed. PMID- 2916857 TI - Lack of teratogenic and mutagenic effects of nitrite on mouse fetuses. AB - To assess embryotoxic effects of sodium nitrite, pregnant ICR mice were given drinking water containing sodium nitrite at a concentration of either 100 or 1000 mg/L on days 7-18 of gestation. There were no significant differences between treated and control groups in measures of developmental toxicity, e.g., litter size, fetal weight, and number of resorbed or dead fetuses. The incidences of external and skeletal malformations in fetuses of treated groups were not significantly different from those in the controls. No significant increase was observed in the frequency of gaps and breaks of liver cell chromosomes in fetuses exposed in utero to sodium nitrite. Teratogenic and mutagenic effects of sodium nitrite were absent in mice at the doses used. PMID- 2916856 TI - Pulmonary function in wood workers exposed to formaldehyde: a prospective study. AB - Employees exposed to formaldehyde in the woodworking industry (N = 47) and nonexposed control subjects (N = 20) were examined in 1980 by spirometry and the nitrogen washout technique. A transient impairment of lung function was noted over a work shift. Five years later, 21 subjects were still experiencing exposure to formaldehyde. A transient decrease in lung function was again found over a work shift, as evidenced by a reduction in forced mid-expiratory flow (FEF25-75) of 0.15 l/s and an increase in closing volume (CV%) of 3.0% in nonsmokers. Significant decreases in forced expired volume in 1 s as a percent of forced vital capacity (FEV1.0/FVC) and FEF25-75 were also noted over the 5 y in nonsmokers (0.4% and 0.2 l.s/y, respectively, after correction for normal aging). After 4 wk of no exposure (holidays), FEF25-75 and forced expired vital capacity (FVC, FEV1.0) returned to normal in the smoking group. Lung function in smokers improved less during the holiday. A dose-response relationship was found between exposure to formaldehyde and decrease in lung function. Thus, industrial exposure to formaldehyde causes transient lung function impairment over a work shift, with a cumulative effect over the years. The impairment, however, can be reversed with 4 wk of no exposure. PMID- 2916858 TI - Deaths from gallstones. Incidence and associated clinical factors. AB - The purpose of this study was to determine the incidence of death as the initial manifestation of cholelithiasis. Records of patients who died or underwent cholecystectomy for gallstone-related disease at Duke University Medical Center between 1976 and 1985 were reviewed. Thirty patients died, six of whom (20%) had previous episodes of biliary pain and stone documentation. Twenty-four (80%) were asymptomatic (three with previous incidental diagnosis of cholelithiasis). Reason for admission included acute cholecystitis (nine), pancreatitis (eight), biliary pain (six), cholangitis (four), jaundice (one), and endocarditis (one). Three patients died of gallstone complications without surgical intervention; one patient had renal failure and two had septicemia. Other causes of death were: sepsis (seven patients), cardiac failure (six), pulmonary complications (four), renal failure (three), cerebrovascular accident (three), liver failure (two), pancreatitis (one), and gastrointestinal bleeding (one). During this period, 1731 cholecystectomies were performed without mortality. In this group, the patients were younger (50 +/- 8 years vs. 64 +/- 13 years, p less than 0.001), and had a lower incidence of cirrhosis (p less than 0.001) and diabetes (p less than 0.002). The sex ratio was inverted (p less than 0.001). This study demonstrates that death from gallstones is uncommon (three cases per year), as is death from their initial clinical manifestation (1.2%). The risk of death is two- and ninefold higher in patients with acute cholecystitis or acute pancreatitis. Age, cirrhosis, and diabetes are important determinants of outcome. PMID- 2916859 TI - The effects of amiloride on biliary calcium and cholesterol gallstone formation. AB - Recent studies indicate that gallbladder absorption increases during the early stages of experimentally-induced cholesterol gallstone formation. The purpose of the present study was to ascertain whether pharmacologic inhibition of gallbladder ion transport and absorption reduces the incidence of experimentally induced cholesterol gallstones. Prairie dogs were fed either a control chow or a 1.2% cholesterol-enriched chow for 15 days. One group of cholesterol-fed animals received saline via an orogastric tube; another group received amiloride, a drug known to inhibit in vitro ion transport in the prairie dog gallbladder. The incidence of gallstones in cholesterol-fed animals was reduced from 83% to 13% (p less than 0.025) when the animals were treated with amiloride; this occurred despite a cholesterol-saturation index comparable to that observed in gallstone animals. Additionally, although biliary calcium decreased in the gallbladder, hepatic bile did not in the amiloride-treated animals. These data provide further evidence that altered gallbladder absorption and increased biliary calcium are important factors in the pathogenesis of cholesterol gallstones. PMID- 2916860 TI - A multivariate analysis of preoperative risk factors in patients with common bile duct stones. Implications for treatment. AB - A multivariate analysis of 30 preoperative risk factors was undertaken in 248 patients who underwent surgery alone for common bile duct (CBD) stones and in 190 patients who had endoscopic sphincterotomy (ES), 77 of whom subsequently also had surgery. Independently significant risk factors in those undergoing surgery were the serum bilirubin level, the use of preoperative ES, and the presence of medical risk factors; in patients undergoing ES, only the serum bilirubin and albumin, but not medical risk factors, were of independent significance. The major implications of this study are, first, that high-risk patients should be treated by ES without subsequent surgery, and second, that "fit patients should be treated by surgery alone without routine preoperative ES. PMID- 2916861 TI - Surgical management of alimentary tract duplications. AB - Alimentary tract duplications are unusual anomalies that may require surgical intervention in the neonate, infant, and occasionally in the older child. The clinical presentation of patients with alimentary tract duplications includes bleeding, abdominal pain, intussusception, and respiratory distress, or it may be an incidental finding on either abdominal examination or chest x-ray. A review of 96 patients with 101 duplications seen over the last 37 years is reported herein. Twenty-one duplications were confined to the thorax; three were thoracoabdominal, and 77 were abdominal. Seventy-four patients presented as infants less than 2 years of age, and 22 patients were older. Ectopic gastric mucosa was found in 21 duplications, and pancreatic tissue was found in five. Seventy-five duplications were cystic and 26 were tubular. Ultrasonography, computed tomography (CT), and myelography are helpful diagnostic tools. Ninety-four of the 96 patients underwent surgical management for their duplications. One duplication was found at necropsy, and one patient was asymptomatic and did not undergo operation. A single death occurred in a 2-day-old infant who had intrauterine volvulus and meconium peritonitis. Management was based on the age and condition of the patient, the location of the lesion, whether it was cystic or tubular and communicating with the true intestinal lumen, and whether it involved one or more anatomic locations. Generally, total excision was preferred, but staged approaches were sometimes necessary. PMID- 2916862 TI - Tumor DNA content in resectable, primary colorectal carcinoma. AB - Tumor DNA content was measured in patients with colorectal carcinoma in order to determine whether tumor ploidy was a prognostic indicator independent of standard clinical and pathologic characteristics. One hundred forty-seven patients were analyzed who had their primary resectable colorectal carcinomas resected with curative intent from 1974 to 1981. Aneuploid colorectal cancers (i.e., tumors with abnormal DNA content) tended to be less well-differentiated, to invade the serosa or extend beyond, and to have lymph node metastases rather than diploid tumors (i.e., tumors with normal DNA content). A significantly increased rate of recurrent disease was demonstrated in patients with aneuploid tumors as opposed to those with diploid tumors (46.7% vs. 4.8%, respectively [p less than 0.001]). In addition, patients with aneuploid tumors exhibited a significantly decreased disease-free and overall survival in comparison with patients with diploid colorectal carcinomas. A Cox regression analysis demonstrated that tumor DNA content was the single most important factor in predicting recurrence or death from colorectal carcinoma. PMID- 2916863 TI - Preoperative irradiation for rectal cancer. Improved local control and long-term survival. AB - Between July 1975 and July 1986, 112 patients with adenocarcinoma of the rectum were treated using preoperative irradiation followed by excisional surgery on the colorectal surgery service of Jewish Hospital at Washington University Medical Center in St. Louis. There were 68 men and 44 women in this study, with ages ranging from 19 to 94 years of age. In all cases, the rectal cancers were believed to be transmurally invasive based on initial clinical examination. Included in this group were 13 patients with poorly differentiated tumors and 51 patients with tumors fixed to surrounding tissues. Between 1975 and 1980, we used 2000 cGy preoperative irradiation followed by immediate excisional surgery to treat 22 patients. Excisional surgery for cure was divided between abdomino perineal resection of the rectosigmoid in eleven patients, low anterior resection of the rectosigmoid in eight patients, and a low Hartmann's procedure in three patients. Five-year survival for 20 patients with potentially curable lesions (Dukes' A, B, and C), was 85%, and there was no local recurrence. Between 1980 and 1986, 90 patients were treated with 4500 cGy preoperative irradiation over a 5-week period followed by a 6-week waiting period, before excisional surgery. There were 72 patients with Dukes' A, B, and C lesions. Fifty patients underwent abdomino-perineal resection of the rectosigmoid, 33 patients underwent low anterior resection of the rectum, and seven patients underwent a low Hartmann's procedure. Five-year survival was 86%. Local recurrence was 1.8%. Tumor fixation and histologic dedifferentiation were the only factors that influenced survival. Five-year survival of patients with fixed poorly differentiated tumors was 27% as compared to 87% in patients with nonfixed well-differentiated tumors (p less than 0.0001). Tumor fixation was not a significant factor in itself. Preoperative external beam irradiation improves survival, local control, and resectability in patients with rectal cancer. This effect may be due to the treatment of the "tangential" margins and local lymph node metastases. Preoperative staging can be accomplished by determining fixation and differentiation of the tumor when preoperative irradiation is used. PMID- 2916864 TI - Pharmacologic modulation of experimental postischemic hepatic function. AB - The present study evaluated and compared the effects of SRI 63-441, a potent platelet activating factor antagonist, superoxide dismutase (SOD), an oxygen free radical scavenger, and ibuprofen, a cyclooxygenase inhibitor on hepatic function after 90 minutes of warm ischemia. After warm ischemia, livers were harvested and underwent 90 minutes of warm, oxygenated, sanguinous perfusion on an isolated liver perfusion apparatus. Pretreatment of donor animals with 20 mg/kg intravenous (I.V.) SRI 63-441 5 minutes before induction of total hepatic ischemia resulted in significantly increased bile production, a significant decrease in transaminase release, and a higher tissue adenosine triphosphate (ATP) content when compared with ischemic nontreated controls. SOD resulted in improved bile production and decreased transaminase liberation only when present in the perfusate at the time of in vitro reperfusion. Ibuprofen did not improve postischemic hepatic function in this model. Electron microscopy revealed patchy hepatocellular vacuolization with an intact sinusoidal endothelium in all ischemic livers. However, the degree of damage was less severe in the livers from those rats pretreated with 20 mg/kg SRI 63-441. This study demonstrates that SRI 63-441 pretreatment significantly reduces hepatic warm ischemic injury, and in the present model, appears superior to two other agents that have been advanced in the treatment of ischemic injury. The use of such agents singly or in combinations have important implications as regards gaining a better understanding of the basic mechanisms in organ ischemia, and moreover, for therapeutic applications in organ ischemia and preservation. PMID- 2916865 TI - Vascular occlusions for liver resections. Operative management and tolerance to hepatic ischemia: 142 cases. AB - The intra- and early postoperative courses of 142 consecutive patients who underwent liver resections using vascular occlusions to reduce bleeding were reviewed. In 127 patients, the remnant liver parenchyma was normal, and 15 patients had liver cirrhosis. Eighty-five patients underwent major liver resections: right, extended right, or left lobectomies. Portal triad clamping (PTC) was used alone in 107 cases. Complete hepatic vascular exclusion (HVE) combining PTC and occlusion of the inferior vena cava below and above the liver was used for 35 major liver resections. These 35 patients had large or posterior liver tumors, and HVE was used to reduce the risks of massive bleeding or air embolism caused by an accidental tear of the vena cava or a hepatic vein. Duration of normothermic liver ischemia was 32.3 +/- 1.2 minutes (mean +/- SEM) and ranged from 8 to 90 minutes. Amount of blood transfusion was 5.5 +/- 0.5 (mean +/- SEM) units of packed red blood cells. There were eight operative deaths (5.6%). Overall, postoperative complications occurred in 46 patients (32%). The patients who experienced complications after surgery had received more blood transfusion than those with an uneventful postoperative course (p less than 0.001). The length of postoperative hospital stay was also correlated with the amount of blood transfused during surgery (p less than 0.001). On the other hand, there was no correlation between the durations of liver ischemia of up to 90 minutes and the lengths of postoperative hospital stay. The longest periods of ischemia were not associated with increased rates of postoperative complications, liver failures, or deaths. There was no difference in mortality or morbidity after major liver resections performed with the use of HVE as compared with major liver resections carried out with PTC alone, although the lesions were larger in the former group. It is concluded that the main priority during liver resections is to reduce operative bleeding. Vascular occlusions aim at achieving this goal and can be extended safely for up to 60 minutes. PMID- 2916867 TI - A multivariate analysis of determinants of survival for patients with squamous cell carcinoma of the head and neck. AB - The prognosis for patients with squamous cell carcinoma of the head and neck remains poor, despite refinements in conventional therapy and experimental protocols using alternative treatment modalities. Clinical characteristics reported to influence survival have included age and sex of the patient, the therapy used, location of the primary tumor, and stage at initial presentation. However, such variables are highly correlated, and previous reports have lacked sufficient statistical analysis to assess the independent influence of these competing variables on survival. To better define the principal determinants of survival, we used a Cox multivariate regression analysis of 542 patients with invasive squamous cell carcinoma of the head and neck treated exclusively at our institution from 1962 to 1976. All patients were followed for a minimum of 5 years after diagnosis, with 98% complete follow-up achieved. Stage at initial presentation was the single-most important factor influencing survival for all tumor locations (p less than 0.0001). Advanced age (p = 0.001) and location of the primary tumor in the tonsillar area (p = 0.01) were also independently associated with an inferior survival. The type of therapy used and sex of the patient did not significantly influence survival after controlling for stage. These data emphasize the need for early diagnosis and treatment of squamous cell carcinoma of the head and neck and underscore the limitations of current therapeutic approaches. Future investigations should incorporate multivariate statistical techniques whenever possible, and additional efforts must be directed at basic research into the biology and immunologic characteristics of these tumors in an attempt to identify innovative therapeutic modalities. PMID- 2916866 TI - Noncardiogenic pulmonary edema after abdominal aortic aneurysm surgery. AB - Limb ischemia in experimental animals leads to white blood cell (WBC) and thromboxane (Tx)A2 dependent pulmonary dysfunction. This study examines the pulmonary sequelae of lower torso ischemia in 20 consecutive patients aged 63 +/- 5 years (mean +/- SEM) who underwent elective abdominal aortic aneurysm surgery. After 30 minutes of aortic cross-clamping, plasma TxB2 levels had risen from 77 +/- 26 pg/ml to 359 +/- 165 pg/ml (p less than 0.01) and was temporally related to increases in mean pulmonary artery pressure (MPAP) from 18 +/- 1 to 23 +/- 3 mmHg (p less than 0.01), as well as to increases in pulmonary vascular resistance (PVR) from 0.07 +/- 0.02 to 0.12 +/- 0.02 mmHg sec/ml (p less than 0.01). Each time that the aortic clamp was repositioned and with final declamping, after 83 +/- 10 minutes, there were further increases in MPAP to a peak of 32 +/- 2 mmHg (p less than 0.01) and in PVR to 0.26 +/- 0.030 mmHg sec/ml (p less than 0.01), corresponding to a plasma TxB2 level of 406 +/- 177 pg/ml (p less than 0.01). MPAP and PVR returned to baseline values within 30 minutes of declamping. Ten minutes after removal of the aortic clamp, platelet levels had fallen from 180 +/ 41 to 97 +/- 17 X 10(3)/mm3 (p less than 0.01) and WBC levels from 8900 +/- 1100 to 4700 +/- 400/mm3 (p less than 0.01). Both platelets and WBC returned towards normal levels, but at 24 hours, while WBC was elevated at 13000 +/- 900/mm3 (p less than 0.01), platelets were 44% of baseline at 135 +/- 14 X 10(3)/mm3 (p less than 0.01). Four to 8 hours after surgery, pulmonary dysfunction was manifest by increases in physiologic shunt from 9 +/- 2% to 16 +/- 2% (p less than 0.01), and peak inspiratory pressure (PIP) from 23 +/- 2 to 33 +/- 2 cmH2O (p less than 0.01). Chest radiography demonstrated interstitial pulmonary edema in all patients, whereas pulmonary artery wedge pressure was 12 +/- 2 mmHg, excluding the possibility of left ventricular failure. After 24 hours, pulmonary edema had resolved, and the PIP and PaO2 had both returned to baseline. These data indicate that reperfusion of the ischemic lower torso leads to the synthesis of TxA2, an event temporally related to pulmonary hypertension and transient leukopenia with subsequent pulmonary microvascular injury manifest by interstitial edema. PMID- 2916869 TI - How urgent is 'urgent' hypertension? PMID- 2916868 TI - The CHAT classification of stroke. AB - Current terminology for clinical episodes relating to stroke is inconsistent and unclear, does not permit inclusion of data regarding the location and magnitude of extracranial and intracerebral arterial disease, does not coincide with existing classifications in Europe, and characterizes a hemispheric entity only, as opposed to a global description including prior symptoms in both hemispheres. A new classification system (CHAT) has been designed to deal with these problems, including the current clinical presentation, historical clinical episodes, the site and pathologic type of arterial disease, and information regarding abnormalities of the brain. Using this system, a retrospective review of 480 consecutive carotid endarterectomies is presented, demonstrating the advantages of the CHAT classification. Data include a significant difference in the probability of survival after carotid endarterectomy for asymptomatic stenosis in patients with prior symptoms on the opposite side, as well as a significant difference in the probability of stroke-free survival between patients with amaurosis fugax and those with prior carotid cortical symptoms (TIAs) as the presenting clinical condition. The CHAT classification is suggested as a significant advance in the reporting of all surgical cerebrovascular disease experience, and has particular implications for the current randomized trials between medical and surgical therapy for carotid artery disease. PMID- 2916870 TI - Bromocriptine and pleuropulmonary disease. PMID- 2916871 TI - Oral nifedipine vs oral clonidine in the treatment of urgent hypertension. AB - Fifty-one patients with urgent hypertension were treated in the emergency department with either oral nifedipine or oral clonidine in a randomized double blind prospective study. Nifedipine was administered as a single dose of 20 mg. Clonidine was administered as an initial dose of 0.1 mg with hourly doses of 0.1 mg. Nifedipine was successful in reducing diastolic blood pressure in 83% of the patients within 45 minutes and in 96% of the patients within two hours, with a mean reduction in systolic blood pressure of 47 mm Hg and diastolic blood pressure of 29 mm Hg. Thirty percent of those who initially responded to nifedipine experienced a subsequent increase in diastolic blood pressure to pretreatment levels within three hours. Clonidine was successful in reducing diastolic blood pressure in 79% of the patients within four hours, with a mean reduction in systolic blood pressure of 51 mm Hg and diastolic blood pressure of 30 mm Hg. Our results indicate that both nifedipine and clonidine are safe and effective in the treatment of urgent hypertension. Nifedipine had a much more rapid onset of action with a greater initial success rate, and it was free from the sedative side effects of clonidine. We believe that either nifedipine or clonidine may be used as first-line therapy in the treatment of urgent hypertension. PMID- 2916872 TI - Relation of ocular and systemic factors to survival in diabetes. AB - The relationship of survival to systemic and ocular factors in diabetic persons was studied using data collected as part of the Wisconsin Epidemiologic Study of Diabetic Retinopathy. Six years after the baseline examination, 9.5% of 996 insulin-taking people who were younger than age 30 years when their diabetes was diagnosed (younger onset) had died. Of 1370 people whose diabetes was diagnosed after age 30 years (older onset), 35.3% had died. After adjusting for age and sex, longer duration of diabetes, presence of proteinuria, a history of cardiovascular disease, higher blood pressure, diuretic use, a history of smoking, poorer visual acuity, and more severe retinopathy were significantly associated with decreased survival in both groups. Glaucoma was associated with decreased survival in the younger onset group and cataract in the older onset group. These findings suggest that some ocular complications are important risk indicators for death. Their presence in diabetic patients suggests the need for frequent examinations to detect systemic complications and to intervene to minimize their effect. PMID- 2916873 TI - Idiopathic bronchiolitis obliterans organizing pneumonia with peripheral infiltrates on chest roentgenogram. AB - We report five patients with chest roentgenograms showing peripheral infiltrates similar to that described for chronic eosinophilic pneumonia (CEP). While lung biopsy specimens (transbronchial and open in two and transbronchial only in three cases) revealed typical changes of bronchiolitis obliterans organizing pneumonia (BOOP) as the predominant finding in all cases, two cases had changes consistent with a resolving CEP. We speculate that (1) it may be common for BOOP to present with peripheral infiltrates, (2) chest roentgenograms showing peripheral infiltrates are not diagnostic of any specific entity, (3) idiopathic BOOP may represent the evolution of untreated CEP, (4) a lung biopsy may be a more appropriate initial approach than the therapeutic trial of corticosteroids when peripheral infiltrates of unknown origin are present, and (5) transbronchial biopsy may be adequate to establish a working clinical diagnosis of BOOP. PMID- 2916874 TI - Postprandial blood pressure decrease in well elderly persons. AB - To learn if postprandial reduction in blood pressure occurs in active, very well elderly persons, we identified 16 such subjects over the age of 75 years, free of cardiovascular disease, taking no drug affecting blood pressure control. Each underwent measurement of seated and standing blood pressure and heart rate before and after a standard breakfast and before and after a volume of water (control). Eight young persons underwent the measurements before and after the meal. The elderly but not the young showed a significant fall in systolic and diastolic pressures after the meal, with heart rate increases in some subjects clearly inadequate for the decline in systemic pressure. No symptoms were seen. But postprandial decrease in blood pressure may in some less robust elderly persons be a factor in syncope and falls. This change may also confuse the monitoring of antihypertensive treatment in older outpatients. PMID- 2916875 TI - Significance of Histoplasma antigen in the cerebrospinal fluid of patients with meningitis. AB - A radioimmunoassay was previously developed for detection of Histoplasma capsulatum antigen in the blood and urine of patients with disseminated histoplasmosis. In this investigation, cerebrospinal fluid (CSF) specimens from 14 episodes of Histoplasma meningitis occurring in 12 patients were tested by radioimmunoassay. Histoplasma capsulatum antigen was detected in the CSF of five patients. Cerebrospinal fluid cultures were positive for H capsulatum in three of these five patients. Antibodies to H capsulatum were found in nine of the 13 CSF specimens tested. The radioimmunoassay for Histoplasma antigen was also positive in the CSF in one of 11 patients with coccidioidal meningitis but not in 17 patients with cryptococcal meningitis. It was concluded that Histoplasma antigen is present in the CSF of some patients with histoplasmosis and chronic meningitis, but cross-reactions may occur in patients with coccidioidal meningitis. PMID- 2916876 TI - Nosocomial febrile illnesses in patients on an internal medicine service. AB - Febrile illnesses commonly arise in hospitalized patients after admission, but most previous studies have been of specific subsets of febrile illnesses. To provide practical information about the problem as a whole, we studied febrile illnesses arising after admission (nosocomial febrile illnesses [NFls]) in 123 inpatients of an internal medicine service who had been afebrile for the preceding week. We compared them with 123 randomly selected patients without NFl. Causes of NFl included infections in 83 cases; noninfectious, inflammatory states in 15; malignancy in 12; ischemia in eight; and procedures in three. Evidence for the cause of the NFl was present at onset in at least 110 of the 123 patients. Despite this, antimicrobial agents were administered to 23 (58%) of 40 patients without infections. Thirty-four patients with NFl died; the NFl contributed to death in 26. In contrast, only eight comparison patients died. "Do not resuscitate" status was present in 32 patients with NFl compared with only 12 comparison patients, and 19 (59%) of the former died. The data from this study provide a comprehensive description of NFl arising in hospitalized internal medicine patients, indicate that the occurrence of a new febrile illness signifies a poor prognosis, and provide a rational basis for management. PMID- 2916877 TI - The therapeutic efficacy of critical care units. Identifying subgroups of patients who benefit. AB - The majority of patients are admitted to critical care units for observation and to facilitate intervention if deterioration occurs or complications develop. We attempted to determine if a reduction in mortality in a subgroup of these patients admitted directly to the critical care units could be identified. A new method using the scientific principles of a randomized trial applied to the case control design was employed. All 1905 patients admitted to the medical service over a three-month period were prospectively evaluated for illness severity and stability. Patients who would not have been eligible for a randomized clinical trial were excluded. Based on the prospective evaluations, four prognostically distinct subgroups of patients were formed. An odds ratio for each of the prognostic groups was calculated, a ratio of greater than 1 indicating a protective effect of direct critical care admission. Only one subgroup of patients, the unstable moderately ill, had an odds ratio greater than 1 (13.3). These results, in association with the results of our previous study, suggest that at the time of admission to the hospital, direct admission to the critical care unit reduced mortality among the unstable moderately ill subgroup of patients. PMID- 2916878 TI - Smoking counseling and preventive medicine. A survey of internists in private practices and a health maintenance organization. AB - Physicians could help a large number of patients quit smoking by taking time to advise them about quitting, helping them plan a date to quit, giving them self help materials, following up, and referring some to smoking cessation programs. To determine the attitudes and practices of internists concerning smoking cessation and selected preventive medical practices, we surveyed a random sample of internists in private practice and in a large health maintenance organization (Kaiser-Permanente Medical Group) in the San Francisco Bay area. Overall, internists consider counseling about smoking to be at least as worthwhile as many other practices, such as screening for breast cancer, and more worthwhile than periodic physical examinations. Despite these beliefs, 57% to 65% of internists reported that they spend two minutes or less counseling smokers during new patient visits. Many internists never use recommended strategies for counseling about smoking: 33% to 44% never help patients plan dates to quit, 68% to 75% never make follow-up appointments with patients primarily about smoking, and 27% to 48% never give smokers self-help pamphlets about quitting. Although they believe that counseling about smoking is worthwhile, internists are not doing as much as they could to help their patients quit. PMID- 2916879 TI - Feasibility and safety of emergency interhospital transport of patients during early hours of acute myocardial infarction. AB - The transfer of patients with acute myocardial infarction from community hospitals to tertiary care facilities for further intervention has become increasingly more frequent due to the emerging role of thrombolytic therapy and percutaneous transluminal coronary angioplasty. To assess the feasibility and safety of early transfer, a prospective analysis of 57 patients who were transported by ground ambulance or helicopter to the University of Massachusetts Medical Center, Worcester, for acute intervention during the early hours of myocardial infarction was conducted. Before transport, the majority (46 [81%]) of patients were having chest discomfort, 13 (23%) were hypotensive, and 12 (21%) were electrically unstable (defined as high-grade ventricular ectopia or nonsustained ventricular tachycardia). During transport, the majority (41 [72%]) continued to have some chest discomfort; however, only two (4%) remained hypotensive. Although five patients (9%) were electrically unstable during transport, the instability was considered noncritical. The distance traveled or the mode of transportation did not adversely impact on these clinical complications. All patients survived transport, and 53 patients (93%) were eventually discharged from the receiving hospital. PMID- 2916881 TI - Limitations to the use of a sensitive assay for serum thyrotropin in the assessment of thyroid status. AB - In the majority of clinical settings, a suppressed serum thyrotropin (s-TSH) level determined by the new sensitive assays is diagnostic of thyrotoxicosis. This has led to its proposed use as a screen for thyroid disease. However, s-TSH may be suppressed in conditions other than thyrotoxicosis. We retrospectively reviewed s-TSH measurements made in a large heterogeneous population to determine in which settings a suppressed value could potentially lead to misdiagnosis. We found that a suppressed s-TSH level was useful in making the diagnosis of autonomous thyroid function and in the assessment of thyroid hormone replacement therapy in patients with primary, but not central, hypothyroidism. Hyperthyroidism caused by either intrinsic thyroid disease or thyroid hormone administration accounted for 83% (111/134) of suppressed values; however, central hypothyroidism, nonthyroidal illness, acute psychiatric illness, or the administration of medication was responsible for this finding in 17% (23/134). While a suppressed s-TSH level is generally excellent in the diagnosis of pituitary suppression by thyroid hormone, in specific clinical settings, a suppressed s-TSH level may be seen in the absence of thyroid hormone excess. The limitations of its use as a first-line screen in those conditions must be recognized. PMID- 2916880 TI - Central hemodynamic changes after ingestion of a meal in patients with coronary artery disease. AB - Thirty-six patients with coronary artery disease participated in a controlled trial of the influence of food intake on central hemodynamic parameters determined noninvasively by radionuclide cardiography. Stroke volume increased considerably (23%) and heart rate was slightly higher (8%) half an hour after the meal, whereas the elevated cardiac output two hours postprandially could be ascribed entirely to relative tachycardia. No significant hemodynamic changes occurred in the patients who fasted. That the left ventricular ejection fraction was increased postprandially (3% to 4%) indicated that food intake had positive inotropic as well as chronotropic effects on the ischemic heart, even in heart failure. Afterload reduction and increased sympathetic nervous activity contribute to the changes, but the primary mechanism may be a change in resistance and blood flow in the intestinal vascular bed involved in digestion. PMID- 2916882 TI - Clinical outcome of patients with a 'low probability' of pulmonary embolism on ventilation-perfusion lung scan. AB - Lung ventilation and perfusion (V/Q) scintigraphy is usually indicated when pulmonary embolism (PE) is a suspected diagnosis. Typically, V/Q scintigraphic interpretation is reported as a "normal," "low," "intermediate," or "high probability" of PE. Although a "low probability" interpretation does not exclude the diagnosis of PE, it significantly reduces the likelihood. We retrospectively analyzed up to one year of follow-up in 90 patients who were clinically suspected of having PE, but in whom V/Q scintigraphy implied a low probability of PE. None of the 90 patients demonstrated clinical evidence of PE subsequent to the V/Q scan. Our findings suggest that significant pulmonary embolism is uncommon and that the clinical course appears to be predictable in patients with a low probability V/Q scan. PMID- 2916883 TI - Passive smoking affects endothelium and platelets. AB - Blood was obtained before and after ten healthy male nonsmokers sat for 20 minutes in open hospital corridors beside men who were already there smoking by their own initiative. Mean values before and after passive smoking were 0.87 and 0.78 for the platelet aggregate ratio, 2.8 and 3.7 per counting chamber for the endothelial cell count, 0 and 2.8 ng/mL for the plasma nicotine concentration, and 0.9% and 1.3% for the carboxyhemoglobin level. No variable changed significantly during control periods in which the subjects sat in a room where smoking was prohibited. Passive exposure to tobacco smoke affected the endothelial cell count and platelet aggregate ratio in a manner similar to that previously observed with active smoking. PMID- 2916884 TI - Physician utilization of laboratory procedures to monitor outpatients with congestive heart failure. AB - Little is known about how different types of physicians use laboratory procedures in the management of outpatients with congestive heart failure. We therefore analyzed data from a national survey of randomly selected general practitioners, internists, and cardiologists to assess their management of outpatients with New York Heart Association class II congestive heart failure. Most of the 2704 respondents (90%) scheduled office visits between two and four months apart. Body weight, serum electrolytes, and chest roentgenograms were followed regularly by 98% or more of respondents, at median intervals of one to two months, three to five months, and 12 to 17 months, respectively. Serum digoxin levels in patients taking digoxin were followed by 90% of respondents at a median interval of 12 months. Echocardiography, radionuclide ventriculography, and exercise testing were used by fewer respondents (81%, 61%, and 61%, respectively), each at a median interval of 18 months or longer. Cardiologists were significantly more likely to follow patients using either echocardiography, radionuclide ventriculography, or exercise testing. The estimated yearly cost of following a class II congestive heart failure outpatient varied nearly fourfold from the lowest quartile of physicians ($303) to the highest ($1167). Cardiologists were disproportionately represented among the high-cost users. In addition, physicians who were younger or who practiced in an urban setting were significantly more likely to be high-cost users. Thus, simple laboratory tests were used most frequently to follow patients with heart failure, but differences in use of more expensive tests led to large differences in cost. Test use for similar patients is affected by characteristics of both the physician and practice setting. PMID- 2916885 TI - Recurrent massive alveolar hemorrhage, crescentic glomerulonephritis, and necrotizing vasculitis in a patient with rheumatoid arthritis. AB - A middle-aged man presented with recurrent alveolar hemorrhage, rheumatoid arthritis, and crescentic immune complex-mediated glomerulonephritis. Nail bed hemorrhages and necrotizing vasculitis were documented concomitantly with the clinical picture of Goodpasture's syndrome. Perusal of the literature disclosed two additional similar cases. It is suggested that Goodpasture's syndrome may evolve in the framework of rheumatoid vasculitis. While immunosuppressive therapy resulted in short-term remission, two of the three patients involved developed late-stage renal failure. PMID- 2916886 TI - Limited weight losses with a gastric balloon. AB - An evaluation of the Garren-Edwards gastric bubble in the treatment of obesity was done. Several clinical trials have compared the effects of behavior therapy with and without the bubble, but the effects of the bubble alone have not been previously evaluated. Ten obese women averaging 91% overweight received the bubble without adjunctive therapy during a 12-week treatment period. Frequent psychological and laboratory measures as well as weight were obtained during the study to explore the possible mechanisms of the bubble's effect and its side effects. Mean weight change was -2.5 kg, with a range of -8.8 to +1.6 kg. Four patients lost more than 3.5 kg, three lost less than 3.5 kg, and three gained weight. The Garren-Edwards gastric bubble alone does not appear to provide significant benefit to most obese patients. PMID- 2916887 TI - Effect of daily charge feedback on inpatient charges and physician knowledge and behavior. AB - Concurrent charge feedback has gained widespread acceptance as a method of minimizing hospitals' losses under the Medicare prospective payment system despite the fact that its effect on patient outcomes, physician behavior, or charges has not been studied in depth. In a controlled trial on two medical wards in an academic medical center, the effect of daily charge feedback on charges was studied. Sixty-eight house staff and 16 teaching attending physicians participated during a 35-week period, taking care of 1057 eligible patients. No significant differences in charges were seen when all patients were included. Since 45% of patients had planned protocol admissions (diagnostic workups or protocol treatment) on which the house staff had little change to impact, a subgroup analysis was performed, excluding these patients. In the remaining patients, a highly significant reduction in mean total charges (17%), length of stay (18%), room charges (18%), and diagnostic testing (20%) was found. In hospital mortality and preventable readmission within 30 days were similar on the two wards. It was concluded that charge feedback alone is effective in a teaching hospital for decreasing charges. PMID- 2916888 TI - Left ventricular response to exercise and autonomic control mechanisms in end stage renal disease. AB - Left ventricular (LV) function during rest and during exercise was evaluated in patients with end-stage renal disease (ESRD) in whom other causes of LV dysfunction were eliminated through rigid selection criteria. Autonomic function was also assessed in these patients with Valsalva's maneuver and plasma catecholamine determinations. Echocardiography and radionuclide ventriculography in the group with ESRD revealed no abnormalities of LV wall motion or ejection fraction. During graded exercise, patients with ESRD achieved 85% of age predicted heart rate, and no differences in exercise tolerance or LV function were observed. Valsalva's response was abnormal in patients with ESRD, and post exercise the norepinephrine level was markedly increased (12.5 +/- 1.43 vs 8.28 +/- 0.82 nmol/L). Our results fail to indicate an independent adverse effect of ESRD on LV function. PMID- 2916890 TI - Fatal small-bowel necrosis and pulmonary hypertension in sickle cell disease. AB - Initial enthusiasm for the use of vasodilators to improve pulmonary hemodynamics and symptomatic status in pulmonary hypertension of diverse etiologies has been tempered by the high incidence of serious complications, especially hypotension. However, the unrelenting hypoxia of pulmonary hypertension without treatment and the improved pulmonary hemodynamics and symptomatic states of some patients during vasodilator therapy provide the rationale for a therapeutic test of vasodilators in hemodynamically monitored patients. We report that vasodilator therapy in a patient with severe hypoxia due to pulmonary hypertension and sickle cell crisis was fatally complicated by hypotension and extensive small-bowel infarction. PMID- 2916889 TI - Once-daily irrigation of long-term urethral catheters with normal saline. Lack of benefit. AB - Urinary incontinence is often managed with a long-term urethral catheter after other methods have failed. Such urethral catheterization is associated with polymicrobial bacteriuria, catheter obstruction, fever, bacteremia, urinary tract stones, and death. Periodic catheter irrigation is a common but untested management procedure intended to prevent catheter obstruction, fevers, and/or bacteremia. To evaluate this technique, we performed a randomized crossover trial comparing ten weeks of once-daily normal saline irrigation with ten weeks of no irrigation in 32 long-term catheterized women. The incidence of catheter obstructions and febrile episodes and the prevalence and species of bacteriuria were similar whether examined as completed crossover patients (N = 23) or as partially completed trials (N = 9). Once-daily irrigation with normal saline of long-term urethral catheters is a time-consuming and costly procedure that is unlikely to have an impact on the morbidity associated with such catheters. PMID- 2916891 TI - Left atrial myxoma associated with systemic AA amyloidosis. AB - A 76-year-old woman presenting with generalized amyloidosis of the AA-type protein was found to have a left atrial myxoma. Retrospective estimation of the concentration of SAA protein, a serum precursor of AA amyloid, before and after surgical removal of the myxoma, showed that the SAA protein had disappeared after the operation. A common manifestation of myxoma is the development of a severe inflammatory syndrome that sometimes simulates rheumatic fever or bacterial endocarditis. However, to our knowledge, it has never been described in association with amyloidosis. We suggest that atrial myxoma should be added the list of neoplastic and inflammatory diseases predisposing to AA amyloidosis. PMID- 2916892 TI - Atrial fibrillation. Cause and time of onset. AB - To characterize groups of patients presenting at the emergency room with atrial fibrillation (AF) according to the various causes of AF and the time of its onset, 704 medical files from the Beilinson Medical Center (Petah Tikva, Israel), during an eight-year period, were reviewed. Two thirds of all patients converted to sinus rhythm (SR) within a seven-day in-hospital treatment. The most frequent causes associated with AF were atherosclerotic cardiovascular disease, 55%; rheumatic heart disease, 22.8%; chronic obstructive pulmonary disease, 2.8%; Wolf Parkinson-White syndrome, 2.6%; and thyrotoxicosis, 2.6%. There was a relatively large group of idiopathic AF (4.5%). Best convertors to SR were patients with idiopathic AF (93.9%), then patients with Wolf-Parkinson-White syndrome (88.8%), followed by atherosclerotic cardiovascular disease (71.6%), and thyrotoxicosis (63.2%). Patients with rheumatic heart disease and chronic obstructive pulmonary disease had the lowest percentage of successful conversion to SR--46% and 55%, respectively. We conclude that there are differences regarding gender, age, and possible conversion of AF to SR according to the different causes of AF. PMID- 2916893 TI - Prehospital sudden death: need for immediate effective resuscitation. PMID- 2916894 TI - Correlation between protein-to-creatinine ratio in a single urine sample and daily protein excretion. PMID- 2916895 TI - Intravenous immunoglobulin therapy in human immunodeficiency virus-associated thrombocytopenia. PMID- 2916896 TI - Hypertrichosis lanuginosa in a man with colon adenocarcinoma. PMID- 2916897 TI - The House of God revisited. PMID- 2916898 TI - Pelvic examination pulmonary edema. PMID- 2916899 TI - Urokinase dissolution of a right atrial thrombus. PMID- 2916901 TI - Rhabdoid tumor. An entity or a phenotype? PMID- 2916900 TI - Inhibition of the yeast-mycelial transition and the phorogenesis of Mucorales by diamino butanone. AB - Diamino butanone (DAB), a competitive inhibitor of ornithine decarboxylase (ODC) a key enzyme in polyamine biosynthesis, inhibited the yeast to hyphae transition in Mucor rouxii, induced by transfer from anaerobiosis to aerobiosis, but not the opposite phenomenon. Addition of DAB to anaerobic yeast cells brought about a decrease in ODC and polyamine levels. In these conditions, the aerobic shift produced only a weak increase in ODC activity and no change in polyamine levels. DAB also blocked phorogenesis in M. rouxii and in Phycomyces blakesleeanus. At the effective concentrations DAB did not affect cell growth of either fungus. It is suggested that low, constant levels of ODC and polyamines are necessary for cell growth, and that high transient levels are required during the differentiative steps. DAB, at the concentrations used, affects this last process, but does not interfere with the maintenance level of polyamines. PMID- 2916902 TI - Malignant rhabdoid tumor of the kidney and soft tissues. Evidence for a diverse morphological and immunocytochemical phenotype. AB - Three malignant rhabdoid tumors of the kidney and two extrarenal rhabdoid tumors of soft tissues were studied by light and electron microscopy and by immunocytochemistry for the expression of keratin, vimentin, desmin, neurofilament triplet proteins, epithelial membrane antigen, myoglobin, and HNK-1 (Leu-7). Electron microscopy revealed the characteristic cytoplasmic whorled filamentous inclusions in all tumors. An epithelial phenotype (presence of cytoplasmic tonofilaments) was observed in two tumors (one renal and one extrarenal); and a focal primitive neural phenotype (cytoplasmic processes with neurosecretory granules), in a renal rhabdoid tumor. Strands of basal lamina were seen in two renal and one extrarenal rhabdoid tumors. Evaluation of basal lamina was more difficult in the third renal rhabdoid tumor, in which tissue preservation was not optimal. Primitive attachments were present in all rhabdoid tumors. Immunocytochemical staining supported a diverse phenotype, ranging from epithelial and/or mesenchymal to myogenous and/or neuroectodermal. Simultaneous expression of several of the studied antigenic determinants by the same tumor was noted. The findings suggest that both renal and extrarenal rhabdoid tumors express a diverse morphological and immunocytochemical phenotype. PMID- 2916903 TI - In vitro study of translocation t(4;11) acute leukemia. Sequential range of phenotype. AB - The nature of translocation t(4;11) acute leukemia cells has been widely discussed over the past few years. Many authors report their phenotypic heterogeneity, ranging from apparently common acute lymphoblastic leukemia antigen-positive to monoblastic leukemia, through "promiscuous" phenotype. We studied in vitro phenotypic modulation of three typical cases after induction by 12-O-tetradecanoyl phorbol 13 acetate. The initial phenotype was different in each case, but all of them exhibited changes in morphologic shape, cytochemistry, and immunophenotype; common features appeared after induction by 12-O tetradecanoyl phorbol 13 acetate, including esterase activity, expression of CD 9, CD-15, and CD-18 surface antigens, and monocyte/macrophage morphology. In all cases a B-associated surface antigen, CD-19, persisted. During clinical evolution, some previously reported cases have shown a karyotypic and phenotypic transformation. In one of our cases this phenomenon correlated with in vitro phenotypic modulation of initial blast population. Furthermore, clinical relapses and in vitro modulation always seem to evolve toward a more "mature" phenotype. Those results support the "promiscuous lineage" hypothesis, and point out the usefulness of in vitro studies to express the myeloid potential of this category of acute leukemia, which can be regarded as a model of early hematopoietic differentiation. PMID- 2916904 TI - Electron-microscopic study of systemic myonecrosis due to poisoning by tropical rattlesnake (Crotalus durissus terrificus) in humans. AB - This article describes the ultrastructural study of skeletal muscle biopsy specimens from five patients following envenomization by tropical rattlesnake (Crotalus durissus terrificus). All the patients were bitten in the leg and the biopsy specimens were obtained from the contralateral gastrocnemius muscle in the middle of the lower leg. A wide spectrum of detailed ultrastructural changes involving muscle fibers and microvasculature was demonstrated. Essentially, such lesions included widespread necrotic myofibers intermixed with intact fibers, accompanied by changes in the endothelial lining of the intramuscular blood capillaries and small arterial vessels, reducing their lumens. Since these alterations were observed in biopsy specimens from the limb contralateral to the site of the bite, they clearly demonstrate the systemic myonecrotic action of the venom of a tropical rattlesnake. On the basis of these data, the mechanism of venom-induced myopathy is described. It is postulated that the pathogenesis of systemic myonecrosis due to poisoning by C durissus terrificus is a complex one, probably due to direct damage to cells by the myotoxins of the venom, as well as indirect effects due to ischemia. PMID- 2916905 TI - The probability of finding suitable directed donors. AB - A series of tables based on mathematical calculations is given as guidelines for the number of directed donors needed by members of various ethnic/racial groups to provide a desired number of units of blood with a selected probability of achieving this result. From these tables, certain conclusions can be drawn. Unrelated donors who do not know their blood type are an inefficient source of directed donors. Rh-negative patients are unlikely to obtain enough directed donor units from either related or unrelated donors with confidence unless these donors known their blood type. In general, siblings, parents, and offspring are the most efficient directed donors from the standpoint of compatibility. Cousins, uncles, aunts, nieces, and nephews are not much more likely to be compatible than unrelated donors are. It is easier to obtain suitable directed-donor units among Hispanics than among whites, blacks, or Asians, due to their skewed blood group frequencies. In general, using O-negative directed donors for Rh-positive recipients does not significantly increase the likelihood of finding suitable donors. PMID- 2916906 TI - The effect of hemolysis on creatine kinase determination. AB - Hemolysis can cause falsely elevated creatine kinase (CK) values when spectrophotometric methods of measurement are used. This apparent increase in CK is due to the red blood cell enzyme adenylate kinase. In an attempt to reduce this interference, most commercial CK kits employ adenosine monophosphate and/or diadenosine pentaphosphate as adenylate kinase inhibitors. To determine whether hemolyzed specimens should be accepted for testing, we measured the CK values of 26 serum samples, each with six different concentrations of added hemolysate. The results showed that hemolysis had an additive effect on CK, with an average increase in CK of approximately 10 U/L for every 1 g/L of hemoglobin. In most settings, this increase is not clinically significant. In the case of massive hemolysis, the hemoglobin concentration of the serum can be measured to correct the apparent CK value. The exclusion of hemolyzed specimens is unnecessary. PMID- 2916907 TI - Analysis of lectin binding in benign and malignant thyroid nodules. AB - The lectin binding properties of ten cases each of adenomatoid nodule, follicular adenoma, and papillary carcinoma and five cases of microinvasive follicular carcinoma were examined histochemically and compared with adjacent normal thyroid tissue. Wheat germ agglutinin, concanavalin A, Ulex europaeus agglutinin I, peanut agglutinin, soybean agglutinin, Dolichos biflorus agglutinin, Ricinus communis agglutinin, and Helix pomatia agglutinin were employed. All the lectins but Ulex europaeus agglutinin I, peanut agglutinin, and Helix pomatia agglutinin were bound to thyroid parenchymal cells, colloid and stromal cells, but none uniquely to thyroid parenchymal cells. Helix pomatia agglutinin binding was present in stromal cells but not in parenchymal cells. Ulex europaeus agglutinin I binding to parenchymal cells was weakly positive only in five cases of papillary carcinoma. The binding in adenomatoid and neoplastic cells and their colloid was stronger than in adjacent normal thyroid tissue in all cases examined. Wheat germ agglutinin and concanavalin A binding was most intense among the lectins examined. In papillary carcinoma, lectin binding was observed mostly in the apical cytoplasm of carcinoma cells, whereas a diffuse surface binding pattern was predominant in follicular adenoma and carcinoma, adenomatoid nodules and normal thyroid gland. No consistent differences in lectin binding were found between follicular adenoma and carcinoma, or between adenomatoid nodules and follicular neoplasia. PMID- 2916908 TI - Chronic basal meningitis and vasculitis in acquired immunodeficiency syndrome. A possible role for human immunodeficiency virus. AB - We describe the clinical and postmortem findings in a 57-year-old man with human immunodeficiency virus who presented with neurologic symptoms attributed to stroke. In addition to multiple foci of ischemic necrosis, pathologic examination of the brain showed chronic basal meningitis and vasculitis. No microorganisms were found. The association of meningitis and vasculitis in patients with acquired immunodeficiency syndrome is unusual and the possibility that these conditions may be due to primary human immunodeficiency virus infection is raised. PMID- 2916909 TI - Isolated eosinophilic coronary arteritis and eosinophilic myocarditis. A limited form of Churg-Strauss syndrome. AB - Eosinophilic coronary arteritis is rare, and it occurs principally as a manifestation of cardiac involvement in Churg-Strauss syndrome (allergic granulomatosis and angiitis). A 39-year-old white man, who was an asthmatic, died suddenly and unexpectedly. Autopsy showed isolated eosinophilic coronary arteritis associated with myocardial necrosis, and isolated eosinophilic myocarditis as the cause of death. This limited form of Churg-Strauss syndrome, to our knowledge, has not been reported previously. PMID- 2916910 TI - Independent learning in pathology. Does it work? AB - The sophomore pathology course at the University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, was substantially modified with the intention of promoting guided, independent learning. The emphasis has been shifted from lectures to other modalities of instruction. This article delineates the curricular changes made, describes the instructional modalities used, and reports student performance after two year's experience with the new curriculum. PMID- 2916911 TI - The American Academy of Physical Medicine and Rehabilitation in 1988. PMID- 2916912 TI - Back strengthening exercises: quantitative evaluation of their efficacy for women aged 40 to 65 years. AB - In this prospective study, the efficacy of exercise on the strength of the back extensors was evaluated. Fifty healthy women volunteers, aged 40 to 65 years (mean = 56 years), participated in a back exercise program. Subjects were screened to exclude those with diseases or treatment programs that could affect muscle strength. Seventeen subjects participated in a conventional back strengthening program, consisting mainly of antigravity upper back extension exercises in the prone position. Thirty-three control subjects continued to perform their usual athletic and daily physical activities. The control group were postmenopausal women who had volunteered to participate in a study of the effect of back strengthening exercises on bone mineral density. Subjects were blindly assigned to the control group without any selection procedures. We used this group as the control for this study because two studies were performed concurrently, and it seemed unnecessary to have two control groups. All subjects were instructed in proper posture principles. Physical activity and back extensor strength were evaluated every four to six weeks for three months. Milestones were completed by 16 subjects in the exercise group and 31 control subjects. The strength of the back extensors was significantly increased (p less than 0.001) in the exercise group. This study indicates that the back extensors can be strengthened with conventional back extension exercise. PMID- 2916913 TI - Rehabilitation of the mastectomy patient: a randomized, blind, prospective study. AB - After biopsy confirmation of breast carcinoma, women who were scheduled to undergo a modified radical mastectomy had demographic data collected, goniometric measurements of shoulder flexion and abduction, and functional evaluation of the ipsilateral shoulder performed, and upper extremity circumferential measurements at five levels determined. Patients were then randomly assigned either to a group that received immediate postoperative physical therapy or to one that did not. Results represent the combination of data from a pilot study and this subsequent study following appropriate statistical analysis. Sixty-four women in the treatment group showed a statistically significant increase in shoulder range of motion in both abduction and flexion as compared to 51 women who received no physical therapy. The treated group also had fewer problems with five of the six upper extremity functional tasks that were assessed. There were no significant differences between the groups for length of hospital stay, postoperative complications, or upper extremity edema. The authors conclude that early physical therapy intervention makes a significant contribution to return to normal function without increasing the incidence of postoperative complications or prolonging hospital stay. PMID- 2916914 TI - Ultrasound: effectiveness of treatments given under water. AB - The purpose of this study was to determine whether ultrasound treatments given with a limb immersed in tap water are as effective in heating the tendons overlying a superficial bony prominence as ultrasound treatments given with the applicator and coupling agent in direct contact with the limb. The lateral epicondyle of a pig was treated with the applicator in contact with the limb and with the limb immersed in a water bath with the applicator held 2cm from the skin surface. With a thermocouple inserted into a 20-gauge needle, the temperature elevations in the tendon of the extensor muscles originating at the lateral epicondyle were measured. It was found that the temperatures of the tendons rose into the therapeutic range when the ultrasound was applied directly to the skin surface, but not when treatment was given under water. It is therefore preferable to give ultrasound treatments with the applicator in direct contact with the subject rather than in an immersion bath with tap water as the coupling agent. PMID- 2916915 TI - Functional outcome after delivery of intrathecal baclofen. AB - Patients with multiple sclerosis or spinal cord injury often have severe, disabling spasticity. This is frequently treated with oral medications or with destructive neurosurgical procedures. We report on a group of patients with spasticity not relieved by these methods. These patients were subsequently treated with intrathecal baclofen delivered by an implanted programmable drug pump. Twenty-one patients have received this form of treatment, and the functional status of eight has been tracked by the Patient Evaluation Conference System (PECS) for at least six months. In most cases, spasticity, performance of bowel and bladder programs, and performance of ADL improved after delivery of intrathecal baclofen. The improvements appear to be due to the decrease in hypertonicity and the increased ease of movement (passive or active) in affected extremities. Intrathecal baclofen should be considered as a treatment method in patients with severe spasticity of spinal origin. PMID- 2916916 TI - Orientation Group Monitoring System: an indicator for reversible impairments in cognition during posttraumatic amnesia. AB - During posttraumatic amnesia (PTA), confusion, attention deficits, impaired memory, disorientation, and inability to process external stimuli often preclude accurate assessment of subtle neurologic changes. The Orientation Group Monitoring System (OGMS) has proven to be a simple, useful strategy for assessing cognitive status. Retrospective analysis of weekly aggregate OGMS scores indicated that a decline in performance of 0.23 or greater is clinically significant. Over a one-year period, 27 patients demonstrated significant decrements in OGMS performance, and in 93% of these instances, the decrease was attributable to a medical problem. Adverse effects of medication was the most common etiology of decreased performance (n = 13). Overwhelmingly, the decline in the OGMS score was the first indication of impaired cognition. This monitoring device is therefore useful as an indicator during PTA of declining cognitive function, warranting further medical evaluation. PMID- 2916917 TI - Viscoelastic shoe insoles: their use in aerobic dancing. AB - To determine whether use of viscoelastic insoles would significantly decrease the frequency of musculoskeletal overuse injury in aerobic dancers, 139 high-level aerobic dancers were divided randomly into two groups. The control group received placebo foam insoles and test subjects were fitted with viscoelastic insoles. Subjects used these insoles during dance class for 15 weeks. Injury rates were low in both groups and no statistical difference was found. Pain syndromes were fewer in the group using viscoelastic insoles, but the difference was not statistically significant. About a third of dancers fitted with viscoelastic insoles and a tenth of placebo insert wearers found that the insoles made their shoes too tight to be comfortable. No conclusion can be drawn on whether shock absorbing insoles decrease injuries from aerobic dancing, but use of viscoelastic insoles may improve comfort and provide pain relief for some high-level aerobic dancers if proper fit is achieved. PMID- 2916918 TI - Bladder emptying assessment in stroke patients. AB - The bladder-emptying status of 85 stroke patients admitted to a comprehensive rehabilitation center was evaluated by postvoid residual (PVR) sequential catheterizations. Those patients with incomplete bladder emptying were assessed by scheduled PVRs throughout their hospitalization. Incomplete bladder emptying occurred initially in 48 of the 85 patients and was sustained in 28. Of this group, 22 were able to void voluntarily and 15 were continent. The incomplete emptying group also demonstrated a significantly higher rate of urinary tract infections. Incomplete bladder emptying or urinary retention in stroke patients with apparently normal bladders is a frequent problem which should be addressed as part of the routine rehabilitation management. PMID- 2916919 TI - Anatomic observations in carpal tunnel syndrome as they relate to the tethered median nerve stress test. AB - The Tethered Median Nerve Stress Test (TMNST) has proved to be a reliable clinical tool in the diagnosis of chronic, low-grade carpal tunnel syndrome (CTS). The TMNST consists of hyperextending the index finger at the distal interphalangeal joint with the wrist maintained in a supinated position. Proximal volar forearm pain radiation is experienced by patients with chronic CTS during this maneuver. This investigation shows that significant distal excursion of the median nerve occurs with hyperextension of the index finger and to a greater degree than with hyperextension of the adjacent digits. Pain experienced during the TMNST appears to be vascular in origin and its severity is directly related to the duration of testing. This finding emphasizes the important role of ischemia in chronic entrapment neuropathies. PMID- 2916920 TI - Insulin pump treatment of type I diabetes mellitus in a patient with C6 quadriplegia. AB - A 40-year-old patient with insulin-dependent (Type I) diabetes mellitus since childhood suffered a C6 spinal transection. Recurrent episodes of hypoglycemia resolved after the patient was placed on an insulin pump. The patient is able to set the insulin delivery rate and maintain the pump without assistance. Spinal cord injured patients may lack both the clinical symptoms of, and the ability to respond to, hypoglycemia. The mixing of NPH insulin and regular insulin requires fine motor skills; even with prefilled syringes, the quadriplegic person may have difficulty with subcutaneous injection. The use of an "open loop" insulin pump averts these problems and may provide better glucose control for selected spinal cord injury patients with Type I diabetes. PMID- 2916921 TI - Spasticity: quantitative measurements as a basis for assessing effectiveness of therapeutic intervention. AB - Spasticity, a common problem in upper motor neuron lesions, frequently results in uncontrolled involuntary motion that interferes with function. A quantifiable method related to the mechanical output of the muscle is needed to test and improve therapeutic intervention. A sinusoidal displacement of 5 degrees was used to measure elastic and viscous stiffness around the ankle at frequencies from 3 to 12Hz. To isolate viscoelastic response, the influences of inertia and equipment drag were eliminated. Test-retest correlation values were 0.953 for elastic and 0.992 for viscous stiffness. The elastic stiffness in 13 spastic subjects under nerve block was significantly higher than that of 13 healthy subjects (p less than or equal to 0.05), indicating early changes associated with contracture. Elastic and viscous response is expressed by the total stiffness vector containing both components, the Nyquist diagram. This diagram's pathlength from 3 to 12Hz was calculated and showed high test-retest reliability in healthy subjects. The median pathlength value for the spastic group was 98 Newton meters/radian (N-m/rad) and, for the normal group, 24N-m/rad, a statistically significant difference (p less than or equal to 0.0001). A mathematical model of the spastic response shows that the Nyquist diagram's pathlength relates to reflex loop gain and is independent of the shift in passive properties. The model predicts a shift in passive properties during spastic responses relative to responses measured during nerve block. Thus, subtraction of passive responses measured during nerve block may not isolate the remaining reflex response, but the pathlength measure relating to the reflex response gain was unaffected, allowing evaluation of therapeutic intervention effectiveness. PMID- 2916922 TI - Familial occurrence of primary fibromyalgia. AB - Seventeen families of patients with primary fibromyalgia were studied for evidence of inherited primary fibromyalgia. Fifty parents and siblings were included in the analysis. Twenty-six (52%, mean age 33.5 years) had characteristic symptoms and findings of primary fibromyalgia. Eleven (22%, mean age 28 years) were asymptomatic but had clinical evidence of abnormal muscle consistency to palpation without tender or trigger points. One person had clinical evidence of lupus. Thirteen (26%) had no evidence of fibromyalgia or abnormal muscle consistency. The mode of inheritance was autosomal dominant. Identical twins are described who developed symptoms of primary fibromyalgia within six months of each other, as are two brothers who developed abnormal palpable muscle consistency years before acquiring the characteristic findings of the fibromyalgia syndrome. Primary fibromyalgia may be an inherited condition with a variable latent stage before clinical expression of the disease. PMID- 2916923 TI - Suction cup ground and reference electrodes in electrodiagnosis. AB - An alternative to the taped-disc surface electrodes typically used during monopolar and concentric needle electromyographic studies has been investigated. The use of suction cup surface electrodes in place of the taped metal disc surface electrodes increases patient and operator safety and enhances patient comfort and operator efficiency. A two-channel EMG, with a single active needle and two reference electrodes, was done on patients routinely referred for electromyographic studies. The motor units were stored and compared. Similarly, baseline noise was stored and compared. This study shows that no distortion of motor unit potentials in typically measured parameters, nor alteration in baseline "noise" occurs when using the suction cup electrode in place of the taped metal discs. The safer, more comfortable suction cup surface electrodes do not distort the motor unit potentials that electromyographers are accustomed to interpreting. PMID- 2916924 TI - Principles of geriatric rehabilitation. PMID- 2916925 TI - The stroke rehabilitation outcome study: Part II. Relative merits of the total Barthel index score and a four-item subscore in predicting patient outcomes. AB - Part I of this series described the background of the study; the characteristics of the patient population; and their functional status before onset of stroke, at rehabilitation admission, at discharge, and at six months after discharge. Results at follow-up showed that patients with higher Barthel index scores living in the community were more likely to be satisfied with life in general, to have more person-to-person contacts, and to be more active in community affairs. Part II describes the utility of two sets of data derived from the admission Barthel index (combinations of independent performance of four basic items of the index vs the total score) in predicting the likely range of Barthel index scores at discharge and functional outcomes at six-month follow-up. PMID- 2916926 TI - The Western Neuro Sensory Stimulation Profile: a tool for assessing slow-to recover head-injured patients. AB - The Western Neuro Sensory Stimulation Profile (WNSSP) was developed to assess cognitive function in severely impaired head-injured adults (Rancho levels II-V) and to monitor and predict change in slow-to-recover patients. Slow-to-recover patients are those who remain at Rancho levels II and III for extended periods of time and are candidates for sensory stimulation programs. Although sensory stimulation is considered beneficial, its utility has not been documented, partly because of the absence of formal measurement tools. The WNSSP consists of 32 items which assess patients' arousal/attention, expressive communication, and response to auditory, visual, tactile, and olfactory stimulation. It was administered to 57 patients with a mean age of 29 years at a mean time of eight months after injury. Statistical analyses indicate the WNSSP to be a reliable, valid measure of cognitive function. WNSSP means differ at each Rancho level, and ranges of scores at each level are sufficiently broad to demonstrate improvement within as well as across cognitive levels. Subjects who later improved performed significantly better on initial testing than did those who did not improve, suggesting prognostic ability of the WNSSP. Our data support other investigations which emphasize that some slow-to-recover patients experience significant improvement. The WNSSP can be a useful tool for studying the recovery process and evaluating treatment programs for slow-to-recover patients. PMID- 2916927 TI - Helping traumatically brain injured patients return to work with supported employment: three case studies. AB - Three case studies illustrating the use of supported employment methods to help individuals with severe head injury are presented. Before supported employment intervention, these individuals were unable either to obtain or maintain employment. Neuropsychologic evaluation revealed many intellectual impairments which contributed to diminished employment potential. Through intervention, all three persons were able to obtain and maintain employment. Consecutive number of months employed ranged from 17.5 to 35, and hours worked per week ranged from 30 to 40. Current hourly earnings exceed the minimum wage, ranging from +5.00 to +5.16 per hour. These cases represent a subset within a larger supported employment program, which assists patients with severe traumatic brain injury to reenter the labor force and maintain employment. PMID- 2916928 TI - Brief assessment of cognitive impairment in patients with stroke. AB - The Stroke Unit Mental Status Examination (SUMSE) has been developed to provide a reliable poststroke test of cognitive functioning that may be administered at bedside. SUMSE was designed to assess major cognitive disorders caused by stroke (eg, language disorders, visuoperceptual deficits, and memory disorders) while avoiding, as much as possible, reliance on patients' English language skills and motor movements. SUMSE's reliability and validity were evaluated by administering it to patients on a stroke rehabilitation unit in conjunction with already validated tests. The results indicated that SUMSE has the potential to become a useful tool for the bedside assessment of mental impairment in stroke patients. PMID- 2916929 TI - Energy requirements of gamefield exercises designed for wheelchair-bound persons. AB - This report presents energy requirements of three athletic exercises (power ramp, climber, and chin-ups) in a free-wheeling gamefield developed by the City of Houston for wheelchair-bound persons. Heart rate was monitored by telemetry. Expired gas samples were collected in Douglas bags. Oxygen and CO2 concentrations were determined by mass spectrometry and expired gas volumes by a wet gas meter. Pulmonary ventilation, O2 consumption, and CO2 production were calculated from expired gas samples. Laboratory studies were conducted on eight men with paraplegia and ten untrained, healthy, able-bodied men. The same persons were tested on the gamefield while propelling a wheelchair over the power ramp, the climber, and doing chin-ups. Age and weight were 32 +/- 4yrs vs 31 +/- 6yrs and 79.6kg vs 79.0kg, respectively, for paraplegic and healthy men. Paraplegic men had average heart rates of 133 +/- 11bpm, 133 +/- 19bpm, and 135 +/- 21bpm, respectively, for the power ramp, climber, and chin-ups. Heart rate values for able-bodied men were 136 +/- 26bpm, 139 +/- 24bpm, and 136 +/- 26bpm, respectively, for the same three exercises. The paraplegic men's VO2 measurements were 13.2 +/- 2.2, 11.5 +/- 2.8, and 6.4 +/- 2.9ml/min/kg, respectively, for the power ramp, climber, and chin-ups. The able-bodied men's VO2 measurements were 15.8 +/- 2.8, 15.4 +/- 3.6, and 9.2 +/- 2.8 ml/min/kg for the same exercises. Patients with paraplegia seemed to outperform able-bodied men in all events. Gamefield exercises appeared to tax the cardiorespiratory system at a level comparable to that usually prescribed for training purposes. PMID- 2916930 TI - Running patterns of juveniles wearing SACH and single-axis foot components. AB - Concerns have been raised about the capability of conventional prosthetic foot components to provide adequate support and function for activities other than walking to persons with lower limb amputations. Degenerative changes of the lumbar spine and knee joints have been linked to prolonged asymmetric loading, which may be accentuated when force magnitudes are high, as in running. This study evaluated the extent and location of kinematic and kinetic asymmetries relative to the foot component worn. The running patterns of six children with unilateral below-knee amputations were evaluated on two occasions: first, while wearing the solid ankle-cushioned heel (SACH) component, and second, wearing the single-axis (SA) component. Cinematographic and forceplate data yielded bilateral temporal data, vertical ground reaction forces, joint angular trajectories, and moments. Results indicated that the SACH and SA components performed almost identically, despite the greater excursion allowed by the SA foot. Slower step speed on the affected side was related to significantly lower vertical ground reaction forces (p less than .01). The ankle angular displacement and moment curves revealed the incapacity of either component to stimulate natural foot ankle function, with resulting significant interlimb asymmetries. The ipsilateral knee displayed marked reduction of the initial flexor wave, paired with a reduced extensor moment. Compensations predominated ipsilaterally, as evidenced by the similarity of the contralateral patterns to those of an able-bodied runner, except for a decreased hip flexor moment before toe-off. This study showed that interlimb asymmetries were attributable to the inadequacies of both components. PMID- 2916931 TI - A rapid method for teaching severely brain injured adults how to wash and dress. AB - The use of a rapid method of teaching a severely brain injured patient to wash and dress is described. The patient, who was injured in an automobile accident eight months earlier, remained dependent in self-care after five months in an acute rehabilitation unit. He was then transferred to a Transitional Living Facility where the program was performed. The patient's physical and cognitive status remained unchanged during the program which lasted for 12 treatment days, but he did become independent in washing and dressing. Independence was maintained at six-month follow-up. Issues relating to the individual's severe memory impairment are discussed in terms of the relevance of such impairments to outcome of training techniques. PMID- 2916932 TI - Theory-based neurorehabilitation. PMID- 2916933 TI - Thoracic outlet syndrome. PMID- 2916934 TI - The 38th annual John Stanley Coulter lecture. The Winter of Our Discontent: breaking intolerable time locks for stroke survivors. PMID- 2916935 TI - Conservative surgery and radiation therapy for early breast cancer. Long-term cosmetic results. AB - To evaluate the cosmetic outcome of conservative surgery (CS) and radiation therapy (RT) for early-stage breast cancer and its stability over time, we reviewed the records of 593 patients treated from 1968 to 1981. The breast appearance was scored as "excellent," "good," "fair," or "poor". Median follow-up was 76 months (range, 37 to 186 months). Cosmetic results were generally excellent or good. The percents of excellent, good, fair, and poor results at three years were 65%, 25%, 7%, and 3%, respectively. Patients not receiving adjuvant chemotherapy were more likely than those receiving chemotherapy to have excellent scores at five years (71% vs 40%). Tumor size also influenced cosmetic outcome: 73% of patients with T1 tumors vs 55% with T2 tumors had excellent scores at five years. Our results were stable over time: of 36 patients assessable at seven years whose cosmetic scores were good or excellent at three years, 34 (94%) continued to have good or excellent scores, and only two (5%) deteriorated to fair. We conclude that the cosmetic results achieved with CS and RT are good to excellent in approximately 90% of patients and that these results remain stable for at least seven years. PMID- 2916936 TI - Local recurrent mammary carcinoma failing multimodality therapy. A solution. AB - Chest wall recurrence following radiation and hormonal therapy is an uncommon but serious and disabling condition. A chest wall ulcer secondary to treatment for recurrence also presents the same dilemma. Over the past 35 years, the Thoracic Service at our institution has treated 35 patients for these problems by surgical resection and reconstruction. Eight patients were seen after the first recurrence, six after the second, ten after the third, and ten after the fourth. One patient had chest wall resection with mastectomy when recurrence followed radiation therapy. Following resection of the tumor, 21 patients had reconstruction using mesh or a mesh "sandwich." There were no operative deaths and no respirator need. Twenty patients are alive from five to 120 months, with a median of 50 months. One of 35 patients had chest wall recurrence. Surgical resection of recurrent mammary carcinoma resistant to all other therapy is a viable alternative for both palliation and cure. PMID- 2916937 TI - Hepatectomy prolongs survival of mice with induced liver metastases. AB - Resection of hepatic metastases from colorectal cancer has been shown to prolong survival in some patients. Whether this results from a reduction of tumor burden or is an indirect effect mediated by hepatectomy is questionable. Male C57BL/6Ros 8-week-old mice underwent ileocolic vein injection of a suspension of 0.3 mL of 2 x 10(5) viable liver-derived murine (MCA-38) colonic adenocarcinoma cells. This model produces hepatic metastases in all lobes of the liver. At 7, 14, or 21 days after tumor injection, mice were randomized to receive either 42% resection of the liver or laparotomy alone. Survival in the animals with hepatectomy was significantly prolonged when the hepatectomy was performed 14 or 21 days after tumor injection. PMID- 2916938 TI - Prolongation of survival of nude mice bearing human colon cancer. Treatment with yttrium 90-labeled anti-carcinoembryonic antigen antibody. AB - Nude mice bearing diffuse intraperitoneal carcinomatosis of the human colon cancer cell line LS174T were treated with an anti-carcinoembryonic antigen monoclonal antibody (MAB) that was labeled with yttrium 90 (90Y-ZCE025). Control animals were either untreated or treated with nonspecific 90Y-MAB (90Y-96.5c). The median survival (MS) for untreated animals was 26 days. The MS for specific and nonspecific therapy that consisted of 120 microCi of 90Y-MAB was 69 and 34 days, respectively. No significant improvement in the MS was observed with a second 120-microCi administration of 90Y-MAB given two weeks later. A decreased MS was observed with 80 microCi of 90Y-MAB given every four days for three cycles. In each category, specific therapy had a significant advantage over nonspecific therapy in increased effectiveness and decreased toxicity. The 90Y ZCE025 therapy gave an increased life span of almost 200%. The therapeutic effects with different dosing regimens have important implications for treatment planning. PMID- 2916939 TI - Survival of patients with stage B2 colon carcinoma. The Gastrointestinal Tumor Study Group experience. AB - The Gastrointestinal Tumor Study Group, a multispecialty collaborative clinical research program, executed two studies of surgically resected colon carcinoma, including patients with serosal penetration but no positive regional lymph nodes (stage B2). In the first study, 232 patients with stage B2 disease were operated on and survival was unaffected by therapy. In the stage B2 group, survival was 78% at five years, and is estimated to be 64% ten years after surgery. A second study, begun in 1979, compared survival and recurrence data on patients who underwent surgical resection and were treated postoperatively with fluorouracil and hepatic irradiation vs those who were observed. Hematologic toxicity of the regimen and accumulation of data from the first study caused the termination of randomization of patients with stage B2 disease with continued registration to observation only. One hundred twenty-four untreated patients with stage B2 carcinoma had a five-year survival rate of 77%, confirming the relatively high survival of this group of patients who are treated with surgery alone. Our patients' five-year survival of 78% corresponds favorably to the 87% survival rate anticipated in an age-, sex-, and race-matched cohort of Americans not specifically diagnosed as having cancer. Adjuvant trials, in seeking improved survival, should recognize that our review of 356 patients implies a considerably higher-than-anticipated five-year survival for the patient with stage B2 disease who undergoes surgical resection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2916940 TI - Interactions of human colorectal carcinoma cells with basement membranes. Analysis and correlation with differentiation. AB - The abilities of colorectal carcinoma cell lines to adhere and invade through a basement membrane were examined. The four poorly differentiated cell lines studied were three to four times more adherent and spread to a greater extent following adherence to a basement membrane matrix than the three moderately well differentiated (MWD) lines. One exception was the MWD cell line DLD-2, whose histologic features resembled a signet ring carcinoma. The ability of these cells to invade through a basement membrane model was measured. This assay showed that the poorly differentiated cell lines as well as DLD-2 were three times more invasive than the remaining MWD cell lines. These data indicate that tumor cell adherence can be correlated with invasion through basement membranes. In addition, the ability of colorectal carcinoma cells to interact with the basement membrane seems, in general, to be inversely related to the degree of cytodifferentiation. PMID- 2916941 TI - The desmoid tumor. Not a benign disease. AB - The necessity of aggressive therapy for desmoid tumors has not been clearly established. To evaluate the therapeutic value of adequate resection and radiation therapy, we conducted a retrospective study of 138 patients treated from 1965 through 1984. Univariate analysis revealed five factors predictive of local failure: (1) age between 18 and 30 years, (2) presentation with recurrent disease, (3) partial or limited margin excision, (4) tumor at or close to the microscopic margin of resection, and (5) radiation therapy not administered for gross residual disease. Multivariate analysis identified two of these factors as having independent predictive value for recurrence: (1) presentation with recurrent disease and (2) less-than-adequate margins of resection. The five-year survival probability was 92%, but 11 of the 138 patients died as a consequence of locally uncontrolled tumor. These findings confirm that desmoid tumors are malignant soft-tissue neoplasms that warrant aggressive therapy. PMID- 2916942 TI - Photodynamic therapy for cutaneous and subcutaneous malignant neoplasms. AB - Twenty-seven patients with cutaneous and subcutaneous malignant neoplasms were treated with photodynamic therapy. Therapy was administered to 248 areas during a total of 72 separate treatment sessions after patients received a total of 45 injections of sensitizer. Seven patients had basal cell carcinoma, three had squamous cell carcinoma, three had malignant melanoma, one had liposarcoma, and 12 had breast cancers. One patient had Bowen's disease. Treatment was given either by surface radiation or interstitially. One month after treatment, 48 (67%) of the treatment sessions resulted in a complete response (no clinical evidence of tumor), and 19 (26%) resulted in a partial response (greater than 50% reduction in the number or size of tumors). Fifteen patients were examinable 12 months after treatment, and in this group, 31 treatment sessions were evaluated as a complete response one month after therapy, 15 (48%) of which retained this status at one year after treatment. By comparing the ability of different light delivery instrumentation, it was concluded that the Yellow Springs radiometer (Yellow Springs Instruments, model 65A, Yellow Springs, Ohio) provided the most reliable spot power density readings. Straight-tipped fibers are nonhomogeneous and can result in overtreatment of the central area with necrosis and pain and in undertreatment of the periphery. PMID- 2916943 TI - Plasma ultrafiltration as cancer therapy. AB - Studies of cancer-related immunosuppression reveal the presence of low-molecular weight (less than 10 kilodaltons) serum factors capable of in vitro lymphocyte suppression. Removal of suppressor factors by ultrafiltration (UF) prolongs survival in tumor-bearing rabbits. This study determined the prevalence of low molecular-weight suppressor factors in patients with cancer and normal volunteers and evaluated safety and feasibility of UF in patients with cancer. Intact serum and serum ultrafiltrate from 32 patients with cancer and 24 normal volunteers was examined with mitogen-induced lymphocyte blastogenesis. Eleven (34%) of serum samples from patients with cancer suppressed blastogenesis, while ultrafiltrate was suppressive in 25 (78%). None of the ultrafiltrate from normal volunteers was suppressive. Six patients with cancer underwent UF in a phase I trial, completing 82 sessions. There were no therapy-related complications, and high-performance liquid chromatography showed significant (greater than 90%) posttreatment reduction in serum suppressor factors. PMID- 2916944 TI - Pseudocysts in chronic pancreatitis. Surgical results in 102 consecutive patients. AB - Preoperative symptoms, diagnoses, and postoperative outcomes in 102 consecutive patients with pancreatic pseudocysts were analyzed. Upper epigastric pain, loss of weight, obstructive jaundice, and sudden arterial bleeding from the pseudocyst were the most common preoperative symptoms. Ultrasonography, computed tomography, and endoscopic retrograde cholangiopancreatography were the most useful diagnostic tools in the evaluation of the presence, size, location, and possible pancreatic ductal communications of the pseudocyst. In a single thick-walled pseudocyst, the best long-term results were achieved by internal drainage. Pancreatic resection is justified if the patient already has diabetes or multiple pseudocysts or if the pseudocyst is not amenable to internal drainage. The most fatal preoperative complication was a sudden arterial bleeding from a pseudocyst. In treating this complication, hemostasis with transcystic arterial ligation and external drainage of the pseudocyst gave the best results. PMID- 2916945 TI - Long-term survival in carcinoma of the biliary tract. Analysis of prognostic factors in 146 resections. AB - In 146 consecutive patients undergoing resection for carcinoma of the biliary tract, various tumor characteristics that affected long-term survival of the patients were studied. Patients with gallbladder carcinoma whose tumors had no serosal infiltration or vessel invasion were grossly papillary, or were papillary or well-differentiated adenocarcinoma histologically survived longer than those without these tumor characteristics. In upper-third lesions, patients whose tumors showed no serosal infiltration or vessel invasion, were grossly papillary, were papillary or well-differentiated adenocarcinoma histologically, or were treated with hepatic lobectomy had a higher chance of long-term survival. Patients with the middle-third lesions, whose tumors were grossly papillary or nodular or whose margins were tumor-free, were apt to survive longer. Long-term survival for patients with lower-third lesions was obtained most often in patients without lymph node metastasis or vessel invasion. PMID- 2916947 TI - Treatment of peritoneal mesothelioma. PMID- 2916946 TI - Follow-up of patients with aspirated breast cysts is necessary. AB - A review was conducted of 401 women who presented with breast lumps that proved to be cysts by yielding fluid on aspiration. The aim was to determine the proportion of patients with cancers that masqueraded as cysts and to establish whether short-term follow-up was necessary. After the first visit, six patients had biopsies because of a residual mass or a bloodstained aspirate. Of these patients, two were found to have cancer. After the follow-up visit, 20 further biopsies were carried out for presence of a mass, bloodstained fluid, or recurrent fluid, and two more cancers were diagnosed. Of the four patients with malignancy, only one had an intracystic carcinoma, two had necrotic grade 3 ductal carcinomas, and one had a malignant phyllode tumor. These findings underline the value of a single return visit after cyst aspiration. PMID- 2916949 TI - Distinguishing and improving dysarthria due to facial weakness. PMID- 2916948 TI - Breast cancer diagnosis in the augmented patient. PMID- 2916950 TI - Lyme borreliosis: discovery of the causative agent. PMID- 2916951 TI - Neuropsychological and neurological function of human immunodeficiency virus seropositive asymptomatic individuals. AB - Although individuals with acquired immunodeficiency syndrome (AIDS) are often impaired on a variety of neuropsychological tasks, questions remain as to when neuropsychological decline can be reliably detected during the course of human immunodeficiency virus (HIV) infection. Detailed neuropsychological testing was accomplished on a cohort of 83 immunologically and neurologically intact asymptomatic HIV-infected individuals drawn from a larger pool of 649 US Air Force personnel with HIV antibodies. These asymptomatic subjects were compared with a group of HIV-negative subjects, and no significant differences in neuropsychological functioning were found. No significant neuropsychological differences were found as a function of cerebrospinal fluid abnormalities in these asymptomatic subjects. When data from 13 subjects with immune compromise were included in the analyses, those with abnormal cerebrospinal fluid values performed significantly poorer on a task of verbal memory, suggesting that cognitive dysfunction is antedated by immunological decline. Methodological problems that inhibit specification of the incidence, prevalence, and natural history of HIV-related cognitive impairment are discussed, as are data suggesting that previously published high estimates of the frequency of HIV-related dementia may not be representative of all HIV-infected populations. PMID- 2916952 TI - Aging and Alzheimer's disease. Altered cortical serotonergic binding. AB - The binding of tritiated serotonin and tritiated spiperone to crude membrane preparations from human frontal poles was determined in both controls and subjects with Alzheimer's disease (AD). Using the dopamine-specific receptor antagonist sulpiride, spiperone binding in the cortex was shown to be essentially serotonergic. A decline in both serotonin and spiperone binding was found in normal aging, and an AD-related decrease was found for spiperone binding only. The AD-related decrement of spiperone binding occurred irrespective of patient age and duration of disease. Scatchard analysis indicates that both age- and disease-related decrements represent a decrease in receptor number. PMID- 2916953 TI - A verbal memory test with high predictive accuracy for dementia of the Alzheimer type. AB - The most common early deficit in patients with Alzheimer's disease (AD) is in recent memory. Distinguishing patients with AD from normal elderly individuals, using currently available memory tests, is limited by their lack of suitability for bedside use or for large-scale screening. We have devised a new memory test, a delayed word recall (DWR) test, that is both brief and efficient. It was designed specifically to maximize the likelihood of poor performance in patients with AD and minimize the likelihood of poor performance in normal elderly subjects. The DWR test uses required elaborative processing of to-be-remembered words and delayed free recall. Fifty-five normal elderly subjects and 28 patients with possible or probable AD were tested. The overall predictive accuracy of the DWR test was 95.2%. In addition, scores on the DWR test in normal subjects were not correlated with education or age. The inclusion of the DWR test in a previously studied cognitive detection battery for AD resulted in a considerable improvement in predictive accuracy. PMID- 2916954 TI - A comparison of dementia in Alzheimer's disease and multiple sclerosis. AB - We compared results of comprehensive neuropsychological testing in 42 patients with clinically diagnosed Alzheimer's disease (AD) and in an equal number of patients with clinically definite chronic-progressive multiple sclerosis. Age, sex, and education were controlled using demographically corrected T scores based on a large normal sample. Both groups showed significant impairment on the test battery, but the degree of dementia was more severe in the patients with AD. A deviation score analysis, controlling for overall level of cognitive impairment, revealed significant differences between the groups. Alzheimer's disease was associated with relatively greater impairment of learning, memory, and verbal skills, whereas the MS group showed greater relative impairment of attention, incidental memory, and psychomotor functions. These data suggest that both the degree and pattern of mental impairement differ in patients with AD and patients with multiple sclerosis. Our results support a distinction between "gray matter" and "white matter" dementia, and may help clarify the issue of "cortical" vs "subcortical" dementia by demonstrating neuropsychological differences based on secure neuropathologic distinctions. PMID- 2916955 TI - Incontinence associated with bilateral lesions of putamen. AB - From 1238 postmortem brain examinations, 44 subject cases with bilateral putamen lesions and 44 controls without bilateral putamen lesions were chosen and compared for the presence and severity of incontinence. The lesions were divided into three grades and the incontinence into five degrees of severity. Final results revealed that 39 of 44 subject cases had some degree of fecal incontinence compared with 12 of 44 controls. The subject cases included 14 with degree 4 incontinence while the controls had none. Forty-three of 44 subject cases exhibited urinary incontinence compared with 25 of 44 controls with the degree again being more severe in the subject cases. Using the chi 2 test, the probability that these differences were due to chance is minimal. Therefore, bilateral putamen involvement appears to be a significant factor in the occurrence of incontinence, and further study of this association is indicated. PMID- 2916956 TI - Selective attention in hemispatial neglect. AB - To determine how increasing demands on visual selective attention affect the symptoms of hemispatial neglect, we studied patients with right hemispheric lesions on a cancellation task requiring various degrees of focused attention. In the target only condition, the patients were to cancel all stimuli. In the target nontarget condition, discriminating targets from nontargets did not require close scrutiny, whereas in the target-foil condition, discriminating targets from foils required greater attention to detail. Our findings indicate that increasing demands on visual selective attention adversely affect both exploration of the left side of space and visual discrimination. PMID- 2916957 TI - Prognostic value of electrically elicited blink reflex in neonates. AB - The electrically elicited blink reflex (BR) was evaluated in 80 normal neonates and 12 neonates with neurologic abnormalities. In normal subjects, R1 and bilateral R2 responses were elicited both while awake and in a quiet sleep state. Whereas the R1 response was consistently elicited in the active sleep state, as well as while awake, the ipsilateral R2 response was markedly suppressed and the contralateral R2 response was almost absent. The BR in neonates with neurologic abnormalities showed the following variable results: normal, prolonged latency, or suppressed response at initial recording. Abnormal BRs were detected in most neonates with respiratory or sucking problems. While neonates in whom a suppressed response or prolonged latency persisted for over three months had a poor prognosis, those with normal BRs or early correction of the BR abnormality had almost normal development. The BR appears to be useful not only to evaluate brain-stem function in the neonatal period but also to predict subsequent outcome. PMID- 2916958 TI - Psychogenic respiratory distress. AB - Five patients developed recurrent episodes of psychogenic respiratory difficulty that were superimposed on psychogenic neurologic symptoms. Misdiagnosis resulted in long hospital stays, code blue alerts, intubation, mechanical ventilation, and, in one case, tracheostomy. Patients "learned" psychogenic respiratory distress because their breathing symptoms evoked distinct evidence of anxiety in physicians and staff. In these patients, gain was not incidental but exerted primary control over symptom selection. The behavioral mechanisms involved in the pathogenesis of psychogenic respiratory distress have significant implications for its diagnosis, treatment, and prevention. PMID- 2916959 TI - Spanish toxic oil syndrome neuropathy in three patients with hereditary motor and sensory neuropathy type I. AB - We describe three patients with hereditary motor and sensory neuropathy type I coming from a family who suffered from Spanish toxic oil syndrome with neuromuscular manifestations. Their clinical course neither differed from other kin only affected with the inherited neuropathy nor from other patients with Spanish toxic oil syndrome studied by us. These findings suggest that patients with hereditary motor and sensory neuropathy do not exhibit a special susceptibility to vasculitic neuropathy associated with Spanish toxic oil syndrome. PMID- 2916960 TI - Crossed aprosodia in strongly dextral patients. AB - Two strongly right-handed patients with aprosodia following left hemisphere strokes are described. These patients appear to represent the aprosodia analogue of crossed aphasia--crossed aprosodia--and provide further evidence that the organization of the effective components of language is functionally and anatomically similar to the organization of the propositional components of language in the brain. In addition, both patients evidenced "double-crossed" agraphia involving the left hand. PMID- 2916961 TI - The scope of neurologic practice and care in England, Canada, and the United States. Is there a better way? PMID- 2916962 TI - Cystoid macular edema following cataract surgery. PMID- 2916963 TI - Correlation of asymmetric damage with asymmetric intraocular pressure in normal tension glaucoma (low-tension glaucoma) PMID- 2916964 TI - Choroidal folds in posterior scleritis. PMID- 2916965 TI - Glaucoma in Barbados. PMID- 2916966 TI - Lid retraction therapy with a guanethidine solution. PMID- 2916967 TI - Death associated with acute, multifocal, placoid pigment epitheliopathy. Case report. PMID- 2916968 TI - Ligation of an arteriovenous malformation with the Heifetz clamp. Case report. PMID- 2916969 TI - Automated perimetry. How do we interpret the results? PMID- 2916970 TI - The Hsiao (Resource-Based Relative Value Scale) study. Experiences, impressions, and objections. PMID- 2916971 TI - Acute macular neuroretinopathy and multiple evanescent white dot syndrome occurring in the same patients. AB - A young woman developed acute macular neuroretinopathy in one eye and five years later developed the multiple evanescent white dot syndrome in the same eye. Another young woman developed unilateral multiple evanescent white dot syndrome and central macular lesions typical of acute macular neuroretinopathy that appeared soon after the peripheral macular and juxtapapillary white lesions resolved. The findings in these two patients suggest that these two relatively rare syndromes may have pathogenetic and etiologic features in common. PMID- 2916972 TI - Protracted enlargement of the blind spot in multiple evanescent white dot syndrome. AB - Two patients had protracted blind spot enlargement, photopsia, and no optic disc edema. Both had fundus and fluorescein angiographic findings typical of multiple evanescent white dot syndrome that resolved within several weeks, leaving a persistent enlarged blind spot and photopsia. These clinical findings and an analysis of the literature data suggest that acute idiopathic blind spot enlargement without optic disc edema may be a subset of multiple evanescent white dot syndrome. PMID- 2916973 TI - Visual field interpretation with empiric probability maps. AB - Automated visual field charts may be difficult to interpret partly because of the magnitude and complex nature of normal threshold variability. We devised two types of empiric probability maps in which this variability is taken into account and the significances of measured threshold values are displayed. These maps are highly sensitive to nonobvious but significant paracentral field loss but will at the same time deemphasize false-positive patterns commonly found more peripherally. They also frequently show field defects before these are obvious in conventional threshold printouts. In addition, they differentiate between generalized loss of sensitivity and localized field defects. PMID- 2916974 TI - Vitreous fluorophotometry in carriers of choroideremia and X-linked retinitis pigmentosa. AB - The status of the blood-retinal barrier (BRB) in carriers of choroideremia and X linked retinitis pigmentosa (XLRP) was determined by vitreous fluorophotometry (VF) and compared with that in female control subjects. Electroretinographic (ERG) amplitudes were measured to determine the overall functional integrity of retinal rods and cones. Comparison of the VF results showed an abnormal BRB in at least some carriers of XLRP, particularly those with peripheral fundus pigmentary changes, but not in carriers of choroideremia with even moderately extensive pigmentary changes. The abnormal BRB in XLRP carriers, with or without peripheral fundus pigmentary changes, was associated with at least moderate to moderately extensive reduction in scotopic ERG amplitudes, while the normal VF results in choroideremia carriers were associated with normal scotopic ERG amplitudes. However, in XLRP carriers, mild to modest reductions in ERG scotopic responses were seen in the presence of normal VF findings. PMID- 2916975 TI - Effects of optic atrophy on retinal blood flow and oxygen saturation in humans. AB - Retinal blood flow and oxygen saturation were evaluated in patients with unilateral inner retinal degeneration secondary to neurogenic optic atrophy. Arteriovenous O2 saturation for temporal and nasal vascular segments of the affected eyes, evaluated by retinal vessel oximetry, was 12% +/- 9% higher than in the fellow eyes (seven patients). Blood flow in the temporal retinal arteries of the affected eyes, measured by the laser Doppler technique, was 48% +/- 20% lower than in the fellow eyes (four patients). The combination of these results indicated a 40% +/- 29% reduction in O2 delivery in the affected eyes (four patients), thereby quantifying the decrease in retinal metabolism that resulted from inner retinal degeneration. PMID- 2916976 TI - Comparison of conventional fluorescein angiography film images with a cathode ray tube display. AB - We evaluated the effectiveness of cathode ray tube (CRT) displays in the transfer of diagnostic information to the ophthalmologist. Retinal fluorescein angiography images were used and data were taken using the receiver operating characteristic experimental paradigm. Three ophthalmologists with experience ranging from two to 12 years participated in the study. Sixty-eight images were selected from proof sheets of 800 original images. Next, these images were digitized, then each set was shown on its respective display (slide projection for the proof sheet images and CRT for the digital images). These 68 images were from a variety of patients and represented a broad range of normal and abnormal retinas (including diabetic retinopathy, hypertension independent of diabetes, and sickle-cell disease). Results show (1) that there is no difference between the systems in terms of diagnostic accuracy; (2) that certainty of diagnosis was not a function of the system; and (3) that although there was an effect due to experience of the ophthalmologist, it did not affect diagnosis accuracy. We conclude that CRT displays at conventional video resolutions can deliver the needed diagnostic information as well as film. We also hypothesize that digital enhancement techniques can increase the available diagnostic information beyond that of film. PMID- 2916977 TI - The Wisconsin Epidemiologic Study of Diabetic Retinopathy. IX. Four-year incidence and progression of diabetic retinopathy when age at diagnosis is less than 30 years. AB - Population-based epidemiologic data on the incidence and progression of diabetic retinopathy are important in medical counseling and rehabilitative services and for developing approaches to preventing diabetic retinopathy. We performed a population-based study in southern Wisconsin of insulin-taking diabetic persons diagnosed before 30 years of age. Of the 271 who had no retinopathy at the first visit, 160 (59%) developed it by the time they were reexamined four years later, and 75 (11%) of the 713 free of proliferative diabetic retinopathy developed it. Overall, worsening of retinopathy occurred in 41% of the population, whereas improvement occurred in only 7%. The incidence of proliferative retinopathy rose with increasing duration until 13 to 14 years of diabetes, thereafter remaining between 14% and 17%. These incidence data underscore the need for careful ophthalmologic follow-up of these people. PMID- 2916978 TI - Does pigmentation affect the trabecular meshwork? AB - Pigment has been associated with glaucoma in pigment dispersion syndrome and in intraocular lens-associated pigment dispersion. Human eyes with segmental pigmentation of the trabecular meshwork may provide a controlled model to study the effects of pigment on the meshwork. Nine normal human eye bank eyes with segmental pigmentation of the trabecular meshwork were examined for pigment associated differences in trabecular cellularity or morphology. Cellularity was examined with four methods: cells per histologic section, cells per length of tissue, cells per overall area, and cells per solid tissue. The simplest method, cells per histologic section, gave results equivalent to the other methods. No differences in cellularity or morphology were found between pigmented and nonpigmented areas. PMID- 2916979 TI - A search for lymphatic drainage of the monkey orbit. AB - Colloid solutions of technetium Tc 99m and india ink injected into the retrobulbar space of the cynomolgus monkey outside the extraocular muscle cone were removed from the orbit by the lymphatic vessels of the conjunctiva and eyelids and were then concentrated within the lymph nodes that drained the conjunctival and eyelid areas. Colloid solutions injected into the retrobulbar space inside the extraocular muscle cone did not reach the conjunctiva and did not collect in any lymph nodes over a 24-hour period. Within the orbit, the injected colloids spread along the planes of the connective-tissue septa. No lymphatic vessels were identified within the orbits posterior to the conjunctiva. Small amounts of india ink left the posterior orbit and ultimately entered the contralateral orbit. This posterior pathway did not lead to lymphatic vessels or lymph nodes and therefore does not appear to represent a prelymphatic pathway. PMID- 2916980 TI - Drug binding of ophthalmic viscoelastic agents. AB - When viscoelastic agents that contain hyaluronate sodium are used during anterior segment surgical procedures, it is common for some of the material to remain intraocularly after the surgery is completed. A variety of drugs, used intracamerally or topically following surgery, are also present. These drugs may be bound to the polyanionic hyaluronate molecule. This occurrence may cause drug alterations in therapeutic effectiveness, pharmacokinetics, and toxicity. To investigate the possibility for drug-viscoelastic agent adsorption, in vitro drug binding studies were performed on three commercial viscoelastic agents; undiluted aliquots of Amvisc, Healon, or Viscoat were mixed with radiolabeled D-threo chloramphenicol, dexamethasone, L-epinephrine, or pilocarpine hydrochloride, placed in dialysis membranes, and dialyzed for 24 hours against an isotonic phosphate buffer. The calculated drug binding by a viscoelastic agent ranged from 0% to 1.5%. These extremely low values for in vitro drug uptake by viscoelastic agents made it unlikely that any significant drug-viscoelastic agent interaction would occur in the postoperative eye. PMID- 2916981 TI - Relapsing polychondritis. PMID- 2916982 TI - Management of cosmetically objectionable veins in the lower eyelids. AB - We have examined three patients with cosmetically objectionable prominent veins in the lower eyelids. Segmental interruption of the vessels through multiple skin incisions has proved to be a satisfactory treatment. PMID- 2916983 TI - A 20-gauge intraocular electromagnetic tip for simplified intraocular foreign body extraction. AB - A modified tip for the Bronson intraocular electromagnet has been developed. The tip was machined to a 20-gauge cylinder that can be inserted readily into the eye either through an entrance wound or through a pars plana incision. Placement of the tip of the magnet inside the eye allows the foreign body to impact the tip of the magnet rather than the wall of the eye. PMID- 2916984 TI - A new intraocular aspiration probe with bipolar cautery and reflux capabilities. AB - The design of the Mentor Wet-Field eraser (Mentor O & O Inc, Norwell, Mass) has been modified so as to include fluid aspiration and reflux capabilities. This 20 gauge disposable probe minimizes instrument exchange through sclerotomy ports and provides sensitive control over reflux action by minimizing the dead-space volume over which reflux occurs. Safer manipulation of detached retina, membranes, and clots is therefore achieved. PMID- 2916985 TI - Ophthalmology in Zimbabwe. PMID- 2916986 TI - Increased levels of platelet-activating factor in blood following intestinal ischemia in the dog. AB - The possible role of platelet-activating factor (PAF) in superior mesenteric artery occlusion induced circulatory collapse was studied in anesthetized dogs. PAF was measured by platelet aggregation assay. Identity of PAF-like product in blood was ascertained by thin layer chromatography, high pressure liquid chromatography and alkaline treatment. Low amount of PAF was detected in the mesenteric blood under normal conditions, during reperfusion PAF levels were significantly higher. Pretreatment of the animals with BN 52021, a specific PAF receptor antagonist abolished the fall in mean arterial pressure and the rise in hematocrit due to ischemia/reperfusion. These findings suggest that PAF may play an important role in mesenteric ischemia-induced circulatory collapse. PMID- 2916987 TI - A time-resolved fluorescence anisotropy study of bilayer membranes containing alpha-tocopherol. AB - Rotational mobility in fluid phase dipalmitoylphosphatidylcholine unilamellar vesicles containing alpha-tocopherol has been studied by time-resolved anisotropy measurements of fluorescence from a diphenylhexatriene-phosphatidylcholine conjugate. The results are analysed using a simple wobbling-in-cone model. The diphenylhexatriene probe shows an increasing order parameter and more restricted wobbling with increasing alpha-tocopherol content of the membrane. The diffusional rate for wobbling was found not to change significantly. PMID- 2916988 TI - Effect of retinol and retinoic acid on testosterone production by rat Leydig cells in primary culture. AB - Adult rat Leydig cells, purified by Percoll density gradient centrifugation, were used to determine the effect of retinol and retinoic acid on steroidogenesis. It was found that both retinoic acid and retinol stimulated testosterone production. Although retinol was less potent than retinoic acid, retinol had the greater efficacy. When these retinoids were tested in the presence of a maximal dose of LH, it was found that retinol inhibited LH-stimulated testosterone synthesis whereas retinoic acid had no similar effect. These results demonstrate for the first time that retinol and retinoic acid have a direct effect on Leydig cell steroidogenesis in culture suggesting that retinoids play a role in the maintenance and regulation of Leydig cell function. PMID- 2916989 TI - Estradiol stimulates in vitro the secretion of insulin-like growth factors by the clonal osteoblastic cell line, UMR106. AB - UMR106 cells, a rat osteosarcoma derived clonal line, secreted insulin-like growth factors (IGF) in vitro. The IGF-II levels corrected for the cell numbers were 7-8 times higher than the IGF-I levels in the medium. Both growth factors were higher by 4-5 fold in medium conditioned by rapidly growing cells than in medium conditioned by confluent cells. The addition of 17-beta-estradiol (E) to the culture medium was associated with a statistically significant increase in the IGF concentrations. This increment was metabolite specific, not occurring with 17-alpha-E, the inactive epimer of E. 1,25(OH)2D3 also increased the IGF-I concentration but prior treatment with E blocked the response to 1,25(OH)2D3, demonstrating antagonistic actions of these two hormones on IGF secretion by osteoblast-like cells. PMID- 2916990 TI - Estimation of the lipophilicity of anti-HIV nucleoside analogues by determination of the partition coefficient and retention time on a Lichrospher 60 RP-8 HPLC column. AB - There is a close linear correlation between the log partition coefficient (Pa) of a series of 2'-deoxyriboside (dR), 2',3'-didehydro-3'-dideoxyriboside (ddeR), 2',3'-dideoxyriboside (ddR), 3'-fluoro-2',3'-dideoxyriboside (FddR) and 3'-azido 2',3'-dideoxyriboside (AzddR) derivatives of uracil, cytosine, thymine, guanine, adenine and 2,6-diaminopurine and their retention times (Rt) on a Lichrospher 60 RP-8 HPLC column (correlation coefficient r greater than 0.970). Within each class of compounds the following order of increasing lipophilicity was noted: dR less than ddeR less than ddR less than FddR less than AzddR. A straight-forward structure-lipophilicity relationship for both base and sugar modified purine and pyrimidine 2',3'-dideoxynucleosides could be delineated. PMID- 2916991 TI - The molluscicidal activity of Phytolacca dodecandra. I. Location of the activating esterase. AB - A number of methods have been used to extract molluscicidal saponins from the dried berries of Phytolacca dodecandra. The potency of the extract has been determined to depend on the release of an enzyme found only in the seed and breaking the seed is critical to the extraction process. The enzyme is inactivated by heat of alcohol. The highest potency extract is made from a cold water extraction of finely ground dried berries. PMID- 2916992 TI - Rabbit liver alcohol dehydrogenase: isolation and characterization of class I isozymes. AB - Livers of rabbits contain three classes of alcohol dehydrogenase (ADH) isozymes which are highly analogous to the human classes. Class I ADHs migrate toward cathode on starch gel and are very sensitive to 4-methylpyrazole (4-MePz) inhibition. Class II ADH migrates slowly toward anode and is less sensitive to 4 MePz. Class III ADH migrates rapidly toward anode and is insensitive to 4-MePz. There are one class II, one class III and at least three class I ADH isozymes present in the rabbit liver. The three class I isozymes purified to homogeneity are all dimers with subunit molecular weight of 41700. Two are heterodimers composed of A-, C-chains and B-, C-chains, respectively. The third one is a homodimer, contains only the C-chain. These results indicate that among all the mammals examined, rabbit ADH bears the greatest resemblance to the human enzyme. PMID- 2916993 TI - Molecular analysis of homologous recombination catalysed by human nuclear extract: fidelity and DNase protection. AB - We present a molecular analysis of DNA's resulting from homologous recombination, between two duplex molecules, and catalysed by human nuclear extracts. Sequence analysis of 20 recombined clones (400 nucleotides per clone), in a genetically silent sequence surrounding the recombination initiation or termination site, shows no modification compared to the parental sequence. Transient protection of the DNA's against DNase treatment was brought about by the nuclear extract. This protection was found to be strickly confined to the homologous sequences potentially implicated in recombination. PMID- 2916994 TI - Proton NMR study of the influence on iron oxidation/ligation/spin state on the heme orientational preference in myoglobin. AB - Proton nuclear magnetic resonance spectroscopy has been utilized to demonstrate that the degree of heme orientational disorder within a given myoglobin protein matrix can be a sensitive function of the oxidation/ligation/spin state of the heme iron. For sperm whale deuterohemin-reconstituted myoglobin, the equilibrium was found to strongly favor (5.7 to 7.8 kJ/mol) the X-ray characterized heme orientation in all six-coordinate states, but with a considerable reduction in preference (to 1.6 kJ/mol) in the five-coordinate deoxy state. In native yellow fin tuna myoglobin, changes in heme orientational preferences of approximately 3 kJ/mol occur even between two six-coordinate ferric states differing solely in spin states. PMID- 2916995 TI - Gas chromatographic-mass spectrometric analysis of hexose monophosphate shunt activity in cultured cells. AB - A GC/MS method is described for monitoring the relative amount of glucose degraded to lactate via the hexose monophosphate shunt (HMPS) in neoplastic cells. C6 glioma cells were incubated in medium supplemented with [1-13 C]glucose and medium containing [1-13C]glucose with 0.001 mM phenazine methosulfate (PMS). The ratio of the [13C]lactate to [12C]lactate determined from the measurement of the m/z 219/220 and 117/118 ions of the trimethyl silyl derivative, was used to calculate HMPS activity. PMS increased HMPS activity in C6 glioma cells by 3.2 and 4.8 fold at 2 and 12 hours of incubation respectively. GC/MS results were compared with 1H NMR measurements of the [3-13C]lactate/[3-12C]lactate ratio. The GC/MS method was found to require less sample size and yielded better sensitivity than the NMR method. PMID- 2916996 TI - Calmodulin activity in whole body and fat body tissue extracts of Heliothis virescens larvae. AB - Calmodulin is an activator of many enzymatic activities. Total calmodulin activity in tissue extracts of Heliothis virescens larvae (5th instar), assayed by cyclic phosphodiesterase activation, was 0.48 unit/gm for whole body and 22.2 units/gm for fat body. Specific calmodulin activity was 0.1 unit/mg protein for whole body and 3.0 units/mg protein for fat body. The larval fat body is therefore the main site of calmodulin activity in this lepidopterous larva. PMID- 2916997 TI - Amino acid substitutions in the human glutathione S-transferases confer different specificities in the prostaglandin endoperoxide conversion pathway. AB - The human glutathione S-transferases 1-1 and 2-2, which differ from each other by 11 amino acids, have different catalytic activities against cumene hydroperoxide and t-butyl hydroperoxide. Using prostaglandin H2 as the peroxide substrate, we found that GSH S-transferase 1-1 catalyzed the transformation of prostaglandin H2 to prostaglandin F2 alpha and E2 at a 4:1 ratio whereas GSH S-transferase 2-2 produced primarily prostaglandin D2 and F2 alpha at a 4:1 ratio. Our results indicate that GSH S-transferases catalyze the reduction and isomerization of prostaglandin H2 endoperoxide in vitro. We suggest that the amino acid substitutions between these two isozymes may be responsible for the difference in catalytic specificities. We propose that these isozymes are important reagents for the biosynthesis of various prostaglandins. PMID- 2916998 TI - S-mercuric-N-dansyl-cysteine labels the free sulfhydryl groups of human serum cholinesterase. AB - Human serum cholinesterase (BChE) has a putative sulfhydryl group (Cys-66) which is unreactive toward conventional alkylating agents such as iodoacetic acid, raising the possibility that this group is blocked in native BChE. In order to test this further, we examined the reactivity of BChE towards the sulfhydryl specific reagent S- mercuric-N-dansylcysteine (SMNDC). Stoichiometric binding of 4 mol SMNDC/mol of tetrameric enzyme was observed in fluorescence titration experiments, with retention of catalytic activity. SMNDC remained bound to the protein during SDS-polyacrylamide gel electrophoresis in the absence of reducing agent and the fluorescence pattern observed under U.V. light coincided with the Coomassie Blue stained bands. Addition of excess dithiothreitol to the SMNDC labeled enzyme resulted in the complete removal of bound SMNDC. Thus, Cys-66 appears to be present in the free sulfhydryl form in BChE, analogous to the corresponding free thiol group (Cys-231) of Torpedo californica acetylcholinesterase. As is the case with the latter species, BChE (labeled or unlabeled) is inactivated by 1.0 x 10(-4)M ZnSO4. PMID- 2916999 TI - Cadmium stimulates prostaglandin E2 production and bone resorption in cultured fetal mouse calvaria. AB - The effect of cadmium on bone resorption was studied using isolated fetal mouse calvaria. Cadmium stimulated bone resorption and PGE2 production in a dose dependent manner. The minimal concentration of cadmium which stimulated bone resorption was the same as that stimulated prostaglandin E2 production. The stimulatory effects of cadmium (0.5 microM) on bone resorption and prostaglandin E2 production were completely inhibited by indomethacin. Exogenously added PGE2 (100ng/ml) abolished the inhibitory effect of indomethacin on bone resorption stimulated by cadmium. These results strongly indicate that cadmium stimulates bone resorption via prostaglandin E2 mediated mechanism. PMID- 2917000 TI - Polyamine levels during Xenopus laevis oogenesis: a role in oocyte competence to meiotic resumption. AB - The results presented here show that a decrease in the concentration of total polyamines, due to a decrease in putrescine and spermine, occurs during oogenesis in Xenopus laevis. The microinjection of spermine or spermidine decreases the hormonal responsiveness (maturation) of the fully-grown oocytes. This effect is synergistic with that already described for the microinjection of casein kinase II (Mulner-Lorillon, O. et al. (1987) Eur. J. Biochem. 171, 107-117), a polyamine dependent enzyme. Therefore a decrease in polyamine concentration, via its effect on endogeneous casein kinase II, could constitute one of the molecular changes required for the acquisition of competence to mature. PMID- 2917001 TI - Differential polyadenylation of the mutant vasopressin mRNA during development of Brattleboro rats. AB - In the normal (Wistar) rat vasopressin encoding mRNA first appears at embryonic day 15 as demonstrated by in situ hybridization of hypothalamic sections. In mutant (Brattleboro) rats, which possess a defective vasopressin gene with a single nucleotide deletion, the corresponding transcript is not detectable before fetal day 18. In both rat strains however expression of the structurally related oxytocin gene begins at fetal day 19. Whereas normal and mutant vasopressin encoding mRNAs are identical in size up to at least three weeks after birth, the corresponding transcripts from adult Brattleboro but not from normal rats are markedly larger. This increase in size is due to a longer stretch of poly(A) sequence as demonstrated by treatment of the respective mRNAs with RNase H and oligo(dT). Thus the mutant vasopressin gene transcript is subject to a cellular specific differential polyadenylation process during development. PMID- 2917002 TI - Molecular cloning and nucleotide sequence of human pancreatic prechymotrypsinogen cDNA. AB - The cDNA clone encoding human prechymotrypsinogen was isolated from a human pancreas cDNA library and its nucleotide sequence was determined. The sequence consists of a 16 bp 5' non-coding region, a 789 bp amino acid coding region and a 60 bp 3' non-coding region. The predicted product consists of 263 amino acids, including 18 amino acids for a signal peptide and 15 amino acids possible for an activation peptide. Southern blot analyses using the cloned cDNA as a probe revealed that human genomic DNA carries at least two genes that are related to chymotrypsinogen. PMID- 2917003 TI - Tumor-promoting phorbol esters stimulate bovine cerebral cortex capillary endothelial cell growth in vitro. AB - The active tumor promoters, 12-O-tetradecanoyl phorbol 13-acetate (TPA) and phorbol 12, 13-dibutyrate (PDBu), which activate protein kinase C (PKC), were found to stimulate bovine brain cortex capillary endothelial cell (CEC) proliferation in a dose-dependent manner. 4 alpha-phorbol-12, 13-didecanoate (4 alpha-PDD), known to be inactive for PKC, was without effect in stimulating CEC proliferation. Furthermore, prolonged incubation with TPA led to a decrease in the number of [3H]-PDBu binding sites with a parallel loss of responses of the cells to TPA. Finally, staurosporine, a potent PKC inhibitor, showed a strong antiproliferative effect on CEC (IC50 = 1.3 nM). Therefore, this work suggests that PKC plays a fundamental role in CEC growth. PMID- 2917004 TI - 'A'-esterases. Enzymes looking for a role? PMID- 2917005 TI - Sulfone analogues of taurine as modifiers of calcium uptake and protein phosphorylation in rat retina. AB - The syntheses of five sulfone analogues of taurine are described: 2 aminoethylmethyl sulfone (AEMS), thiomorpholine-1,1-dioxide (TMS), N methylthiomorpholine-1,1-dioxide (M-TMS), (+/-)3-aminotetrahydrothiopyran-1,1 dioxide (APS), and (+/-)3-aminotetrahydrothiophene-1,1-dioxide (ATS). When these compounds were evaluated in the rat retina as modulators of ATP-dependent calcium ion uptake at low calcium ion concentrations (10 microM), AEMS, ATS, and APS were found to be more potent stimulators of ATP-dependent calcium ion uptake than taurine. TMS and M-TMS had no effect. At high concentrations of calcium ions (1.44 mM), taurine, AEMS, ATS, APS, and TMS inhibited ATP-independent calcium ion uptake; AEMS, ATS, and APS were more potent inhibitors than taurine. ATS was the only compound tested (including taurine) that inhibited ATP-dependent calcium ion uptake at high calcium ion concentrations. The effects of the sulfone analogues of taurine on the incorporation of phosphate into retinal proteins were also studied. Taurine, AEMS, ATS, APS, and TMS were equipotent inhibitors of phosphate incorporation (30-45%). M-TMS had no effect. PMID- 2917006 TI - Induction and depression of cytochrome P-450-dependent mixed-function oxidase by a cloned consensus alpha-interferon (IFN-alpha CON1) in the hamster. AB - A novel analogue of human alpha-interferon (IFN-alpha CON1) was tested for its ability to modify the hepatic cytochrome P-450-dependent mixed-function oxidase system in the hamster. This cloned interferon was derived by selecting the most frequently observed amino acid sequences at each position in the known human alpha-interferon subtypes. IFN-alpha CON1 had a biphasic effect on cytochrome P 450 and related drug biotransformation in the hamster causing an initial increase followed by a significant depression. IFN-alpha CON1 also had a biphasic effect on cytochrome P-450 in the lung, adrenal and spleen but only a depressant effect in the kidney. This effect was not due to morphological damage and followed the species specificity for this type of interferon. Both the increase and the decrease in cytochrome P-450 could be prevented by the administration of the protein synthesis inhibitor puromycin. Various isozymes of cytochrome P-450 induced by phenobarbital, beta-napthaflavone and clofibrate were also depressed by this interferon. The results presented in this report suggest that IFN-alpha CON1 interferon will likely depress drug biotransformation in humans because the antiviral effects and the "anti-cytochrome P-450" effect of interferons cannot be separated, and this interferon has antiviral properties in both hamster and human cells. Clinically relevant drug interactions may be common during the concomitant use of this interferon and other drugs that are metabolized by cytochrome P-450. PMID- 2917007 TI - 1,25-Dihydroxyvitamin D3-induced growth restriction of cultured epithelial cells derived from a murine hepatic tumor. AB - Recent evidence suggests that 1,25-dihydroxyvitamin D3 can accumulate in certain presumed non-target tissues, although the mechanism of action of the vitamin in such cells is not understood. Exposure of 77-1/3a mouse hepatic tumor cells, which derived from a non-target tissue of vitamin D action, to 1,25 dihydroxyvitamin D3 in chemically-defined serum-free medium resulted in a dose dependent decline in cellular growth rate and maximal culture population density but did not adversely affect cell viability. Culture of 77-1/3a cells in defined medium containing 10(-7) or 10(-6) M 1,25-dihydroxyvitamin D3 for 150 hr reduced the growth rate to 64 and 50% of control values respectively. Albumin secretion was unaffected by 1,25-dihydroxyvitamin D3 exposure; in contrast, the cellular content of the proliferation-associated protein p35 was reduced by 39%, a decline similar in trend and degree to that observed in other tumor cells exposed to differentiation-inducing agents. It appears that 1,25-dihydroxyvitamin D3 regulates cellular p35 content (within a specific restricted range) as a consequence of proliferative perturbation, rather than differentiated status, of cultured hepatic tumor cells. PMID- 2917008 TI - Improvement of ischemia-reperfusion-induced myocardial dysfunction by modulating calcium-overload using a novel, specific calmodulin antagonist, CGS 9343B. AB - The present paper explores the mechanism of calcium-overloaded cardiac cell exocytosis during reperfusion of ischemic myocardium. A novel specific inhibitor of calmodulin, CGS 9343B, was used to pretreat an ischemic heart in an effort to enhance myocardial preservation. The experimental model employed an isolated in situ pig heart subjected to 120 min of ischemic insult by reversibly occluding the left anterior descending coronary artery, the last 60 min being superimposed with global hypothermic cardioplegic arrest. This ischemic episode was followed by 60 min of revascularization. CGS 9343B enhanced post-ischemic myocardial recovery, as judged by improved regional as well as global myocardial functions, better preservation of high-energy phosphate compounds, and reduced release of creatine kinase. Since this compound blocks calmodulin without inhibiting protein kinase C, the results of this study suggest that calmodulin-dependent kinase, rather than protein kinase C, is primarily involved in expressing calcium overloaded cell exocytosis, and a specific calmodulin antagonist such as CGS 9343B can be used to salvage an ischemic heart from reperfusion injury. PMID- 2917009 TI - The accumulation of cystamine and its metabolism to taurine in rat lung slices. AB - The objective of these studies was to determine the accumulation and fate of the disulphide, cystamine by rat lung slices. Cystamine was accumulated by two active uptake systems that obeyed saturation kinetics, with apparent Km values of 12 and 503 microM, and maximal rates of 530 and 5900 nmol/g wet weight/hr respectively. The high affinity system was competitively inhibited by the diamine, putrescine and the herbicide paraquat, which are themselves accumulated. Thus, this pulmonary uptake process appears to be identical for all three compounds. In contrast, the low affinity process was not inhibited by putrescine, and this process results from the diffusion of cystamine into the cell and its subsequent metabolism. Upon accumulation, cystamine was metabolised, predominantly to the sulphonic acid, taurine, with 10-20% of the intracellular label covalently binding to protein. Conversion to taurine was unaffected by amine oxidase inhibitors, but was decreased after GSH depletion, suggesting that pulmonary cystamine metabolism is glutathione-dependent, and is not mediated by diamine oxidase. Both cystamine and taurine have been implicated as antioxidants, and we suggest that cystamine is actively accumulated by the lung as part of the process to protect pulmonary tissue against oxidative stress. PMID- 2917010 TI - Acetylcholinesterase prophylaxis against organophosphate poisoning. Quantitative correlation between protection and blood-enzyme level in mice. AB - Fetal bovine serum acetylcholinesterase (FBS-AChE, EC 3.1.1.7) was titrated, both in vitro and in vivo, with a highly toxic anti-ChE organophosphate, 7 (methylethoxyphosphinyloxy)-1-methyl-quinolinium iodie (MEPQ). Approximately 1:1 stoichiometry was obtained for the sequestration of MEPQ by FBS-AChE in mice. A quantitative, linear correlation was demonstrated between blood-AChE levels and the protection afforded by exogenously administered AChE in mice when challenged with anti-ChE MEPQ. The results presented in this report demonstrate that such prophylactic measures are indeed sufficient to protect animals against poisoning by as high as an 8 x LD50 dose of organophosphate without the administration of any supportive drug. Despite the relatively large toxic dose, most of the mice that survived the challenge did not show any classical clinical signs of severe anti-ChE poisoning. MEPQ may be considered a suitable model compound for studying the quantitative aspects of the scavenger prophylactic approach described here. PMID- 2917011 TI - Metabolism of diethylene glycol in male rats. PMID- 2917012 TI - Irreversible inhibition of rat striatal dopamine uptake induced by in vitro exposure to DSP4. PMID- 2917013 TI - Effect of khat on the metabolism of erythrocytes. AB - The plant khat "Catha Edulis Forsk" is widely distributed among most East African countries, Yemen and many other areas of the world. Administration of khat extract by the intragastric route in rabbits affected the metabolism of erythrocytes. There is a significant decrease in pyruvate kinase and the level of reduced glutathione (P less than 0.001), and a highly significant increase in both glucose-6-phosphate dehydrogenase and glutathione reductase activities (P less than 0.001) in khat-fed rabbits as compared to controls. On the other hand the activity of uridyl transferase as well as the concentration of 2,3 diphosphoglycerate were not significantly changed in experimental khat-fed rabbits (P greater than 0.5). PMID- 2917014 TI - Peroxidase as a model for reduction of tertiary amine oxides catalyzed by rat hepatic supernatant and microsomal fractions. AB - Rat hepatic microsomal and 100,000 g supernatant fractions catalyzed an NADH- and FMN-dependent reduction of amine oxides. Horseradish peroxidase (HRP) served as a model for the amine oxide reductase located in rat hepatic 100,000 g supernatant fraction. The HRP-catalyzed reaction displayed saturation kinetics with respect to NADH and the amine oxide substrate; however, there was an optimum concentration for FMN after which inhibition was observed at increased concentrations of FMN. The reductase in the 100,000 g hepatic supernatant fraction closely paralleled HRP-catalyzed amine oxide reduction in coenzyme requirements, sensitivity to inhibitors, and substrate specificity. Moreover, the peroxidase activity of HRP and microsomal and 100,000 g supernatant fractions correlated with the NADH- and FMN-dependent amine oxide reductase activities of these enzyme preparations. The NADH- and FMN-dependent amine oxide reductase activity in 100,000 g supernatant fractions, however, did not parallel the aldehyde oxidase activity. Thus, the results indicate that there is an amine oxide reductase in rat hepatic 100,000 g supernatant fraction with catalytic properties that are modeled well by horseradish peroxidase. PMID- 2917015 TI - Solvent dependency of rotational barriers in ethamivan and comparison to nikethamide. AB - Carbon-13 nuclear magnetic resonance (NMR) techniques were employed to examine the effects of solvent environment on rotational barriers in two drugs known to cause widespread stimulation in the mammalian central nervous system: ethamivan and nikethamide. Total NMR bandshape analysis was performed for the exchanging alkyl carbon resonances of these compounds as a function of temperature in six solvent systems: D2O, CH3OD, CH3CH2OD, CDCl3, C6D6 and CF3CH2OH. The rate constants for rotation about the amide bond obtained in this way were used to calculate free energy (delta G++), enthalpy (delta H++) and entropy (delta S++) of activation parameters for this process. Our results indicate that the magnitude of rotational barriers is affected markedly by (1) the size and polarity of the solvent molecules, and (2) the nature of the aromatic ring system attached to the amide grouping. Comparative interpretation of the thermodynamic parameters in light of the structures of nikethamide and ethamivan (in the various solvent systems examined) has further clarified the manner in which hydrogen bonding interactions between solvent molecules and the carbonyl oxygen of these analogues stabilize transition state conformers. PMID- 2917016 TI - Hormonal regulation of the developmental pattern of epoxide hydrolases. Studies in rat liver. AB - Hormonal influences on the developmental pattern of epoxide hydrolases (EH) were investigated in livers from male and female Fischer F-344 rats. During ontogeny, activities of rat liver microsomal and cytosolic epoxide hydrolases (cEH and mEH) increased gradually until puberty when activities in males rose rapidly to become 1.5-fold to 2.0-fold higher than those in females. These sex differences were not observed in the adult rat if males were castrated 24 hr after birth. In castrated males, as well as in females, testosterone propionate (TP, 0.5 mg s.c. in 50 microliters peanut oil) injected on days 1, 3 and 5 postpartum increased mEH and cEH activities at adulthood compared to peanut oil-treated controls. In another study to determine effects on adults of neonatal exposure to a prototype-inducing agent, phenobarbital (PB, 30 mg/kg s.c., qd, in 0.9% saline) was injected in male and female neonates on days 1 through 5 postpartum. Although no long-term effect on mEH activities appeared on days 28, 45 and 60, hepatic mEH activities increased in all treatment groups on days 90 and 120. Collectively, these studies indicate that neonatal exposure to testosterone and PB alters the developmental pattern of EH activities, including final adult levels. Thus, full adult expression of these activities depends on hormonal influences exerted neonatally. PMID- 2917017 TI - Optical spectral studies of ebselen interaction with cytochrome P-450 of rat liver microsomes. AB - Interaction of ebselen, an anti-inflammatory compound of low toxicity, with rat liver cytochrome P-450 is used as a model system to quantify possible interactions of seleno-organic compounds with sulfhydryl groups of intracellular membrane-bound proteins. Ebselen induces a unique difference spectrum (maximum at 405 nm, minima at 385 and 425 nm) after addition to microsomes under in vitro conditions. This spectrum indicates an interaction with the thiolate anion at cytochrome P-450; it can be blocked by previous addition of dithioerythritol. With uninduced microsomes, addition of ebselen converts maximally 50% of the cytochrome P-450 to P-420 in a time-dependent (nearly complete effect within 10 min) and concentration-dependent manner (halfmaximal effect with 50 microM at 1 nmol/ml cytochrome P-450 concentration) in vitro. In phenobarbital- and 3 methylcholanthrene-induced microsomes, 73% and 64%, respectively, of cytochrome P 450 are converted to P-420 in presence of 200 microM ebselen. It is assumed that only certain isoenzymes of the total hepatic cytochrome P-450 are accessible to ebselen. Bovine serum albumin at physiological concentrations and sulfhydryl compounds such as dithioerythritol are effective in preventing this cytochrome P 450 inactivation by ebselen. Specificity studies reveal that variation of the N substituent in the benzisoselenazolone system does not influence cytochrome P-450 inactivation, whereas ebselen derivatives with methylated or glucuronidated selenium moiety as well as diselenides do not convert cytochrome P-450 to P-420. It is concluded that benzisoselenazolones are able to interact with sulfhydryl groups of membrane-associated proteins in vitro. PMID- 2917018 TI - The bispyridinium-dioxime HLo-7. A potent reactivator for acetylcholinesterase inhibited by the stereoisomers of tabun and soman. AB - Purification of (+)-tabun was accomplished by treatment with electric eel acetylcholinesterase (AChE) in order to bind contaminating (-)-tabun and with purified (+)-tabun shown similar properties in reactivation reactions with oximes (pH 7.5, 25 degrees). The bispyridinium-2,4-dioxime HLo-7 is a substantially active reactivator for these inhibited enzymes as well as for human erythrocyte AChE inhibited with (-)-tabun. In contrast, the corresponding bispyridinium-2 monooxime HI-6 does not show any activity at similar reaction conditions. HLo-7 is also much more active than HI-6 when used as a reactivator for electric eel AChE inhibited by some N-unsubstituted derivatives of tabun. Surprisingly, HLo-7 is highly active in reactivating human erythrocyte and rat diaphragm AChE inhibited by C(+)P(+/-)-and C(-)P(+/-)-soman, i.e. at least as active as HI-6, which is the most potent reactivator for soman-inhibited AChE reported so far. To our knowledge, HLo-7 is the first compound reported in literature that shows a potent reactivating activity towards both tabun-inhibited AChE and soman inhibited AChE. PMID- 2917019 TI - Cytotoxic activity of daunorubicin or vindesin conjugated to a monoclonal antibody on cultured MCF-7 breast carcinoma cells. AB - Conjugates were constructed between daunorubicin or vindesin and a monoclonal antibody to human milk fat globule membrane associated antigen. This antibody recognizes a high molecular weight glycoprotein present at the cell surface of human normal and tumour epithelial cells; after specific binding to plasma membrane of cultured MCF-7 human breast carcinoma cells, it is endocytosed and gains access to lysosomes, wherein it is broken down (Aboud-Pirak et al., Cancer Res 48: 3188-3196, 1988). Covalent linkage of daunorubicin (through a succinylated tetrapeptide arm) or of vindesin (through a hemisuccinate arm) yields conjugates with maximal molar ratios (drug molecule/specific IgG under monomeric form, i.e. unaggregated) or 2.0 and 4.5 respectively. The conjugate with daunorubicin inhibits the binding of the 3H labelled antibody to MCF-7 cells as efficiently as the native unconjugated antibody, whereas the conjugate with vindesin inhibits it only by 56%. Both conjugates are entirely stable in plasma and serum; after 24 hr incubation at pH 4.8 in the presence of rat liver lysosomal enzymes, 60 and 33% of daunorubicin and vindesin respectively are released from the conjugates. Adherent non-confluent cultures of cells recognized (MCF-7) or not (Hep-G2, human hepatocarcinoma cells) by the antibody were incubated from 1 hr to 6 days with different concentrations of daunorubicin or vindesin, free or conjugated to the specific or to a control monoclonal antibody. LD50, defined as the drug concentration required to reach 50% of the amount of cell associated protein obtained in the absence of drug were determined at the end of 6 days continuous incubation or after shorter incubation followed by reincubation in drug free medium up to 6 days. Both cell lines are almost equally susceptible to the free drugs. The conjugate between daunorubicin and the antibody appears inactive, even at saturating concentrations of antibody. This could result from the extrusion out of the cells of daunorubicin molecules released from the conjugate, impairing the drug to reach the intracellular concentration required for cytotoxicity. In contrast, conjugation of vindesin to the specific but not to a control antibody restricts the activity of the drug to cells selectively recognized by the specific antibody. However, even after corrections for the loss of immunoreactivity and for the incomplete release of vindesin from the conjugate, cytotoxicity is achieved at higher concentrations or requires longer exposure to the conjugated than to the free drug.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2917021 TI - Metabolic binding of misonidazole to mouse tissues. Comparison between labels on the ring and side chain, and the production of tritiated water. AB - The 2-nitroimidazole, misonidazole, is of current interest as an imaging agent for hypoxic regions in tumors and in vascular disease such as stroke. The basis of this technique is the reductive activation and binding of nitroheterocycles which is much more efficient in the absence of oxygen. The appropriate molecular location for an active isotope on the nitroheterocyclic probe depends on the nature of the metabolites retained in tissues after the parent drug has been cleared. Previous studies with tumor cells in vitro indicated that a ring label (2-14C) and a side-chain label (3H) were retained equally efficiently in the acid insoluble fraction, whereas 1.5 to 3 times more side-chain label was retained in the total pool (acid soluble plus acid insoluble) of metabolites in several normal murine tissues. We show here that the excess side-chain label in six normal tissues, plasma and EMT6 tumors was found entirely in the acid-soluble fraction as a volatile component. This volatile component was tentatively identified as tritiated water. It appeared that, in general, molecular products of misonidazole metabolism were retained in mouse tissues, with the exceptions that a small excess of ring label was found in liver and heart and that tritiated water appeared in the acid-soluble fraction of all tissues. Tritiated water would not be important in imaging studies but could be a factor in studies in which scintillation counting of tritiated nitroheterocyles is used. PMID- 2917020 TI - Comparison of the form(s) of cytochrome P-450 induced by ethanol and glutethimide in cultured chick hepatocytes. AB - In this study, using a combination of immunological and enzymatic characterizations, we compared the forms of cytochrome P-450 induced by ethanol and glutethimide in primary cultures of chicken embryo hepatocytes. Recently we purified a cytochrome P-450 of 50K molecular weight from chicken embryo liver using glutethimide as a prototypic inducer. Antibodies to both this chicken cytochrome P-450 and to rabbit cytochrome P-450 form 3a from the IIE subfamily detected microsomal proteins of 50K induced by either ethanol or glutethimide in cultured chick embryo hepatocytes, indicating the antigenic homology of these subfamilies of cytochromes P-450 among different animal species. However, the antibody to glutethimide-induced chick cytochrome P-450 of 50K inhibited p nitrophenol hydroxylase and benzphetamine demethylase activities 85-90% in microsomes from both ethanol- and glutethimide-treated cells, indicating similar epitopes whose integrity is required for catalytic activity. In contrast, antibodies to rabbit cytochrome P-450 form 3a had little to no effect on these same microsomal activities. Both ethanol and glutethimide induced microsomal p nitrophenol and aniline hydroxylase activities in cultured chick embryo hepatocytes. In microsomes from ethanol-treated cells, the turnover of p nitrophenol per cytochrome P-450 was 2-fold greater than that induced by glutethimide treatment, suggesting that ethanol is inducing a form of cytochrome P-450 that has greater catalytic activity with this substrate than glutethimide induced forms. Thus, in cultured chick embryo hepatocytes, ethanol may induce cytochromes P-450 from both the IIB and IIE subfamilies. PMID- 2917022 TI - Interaction of haloacetonitriles with glutathione and glutathione-S-transferase. PMID- 2917023 TI - Human liver microsomal cytochrome P-450IIE1. Immunological evaluation of its contribution to microsomal ethanol oxidation, carbon tetrachloride reduction and NADPH oxidase activity. PMID- 2917024 TI - A time study on the uptake of estramustine into prostatic tumour 1013L cells in vitro. PMID- 2917025 TI - [Urticaria in general practice]. AB - The vast majority of cases of urticaria and angio-edema are diagnosed and treated by general practitioners. Epidemiologic investigations have shown that 2.5 percent of the population annually seek medical advice for urticaria, and of these 95 percent consult a general practitioner. The available literature, however, is mainly based on materials from specialist clinics, and outpatients hospital departments. The clinical picture of urticaria as seen by the general practitioner differs, however, is essential features from that observed in selected patient groups. Recent studies from the primary health care services have confirmed this observation. PMID- 2917026 TI - [Malignant diseases as secondary findings in forensic autopsies]. AB - In a study of 228 consecutive medico-legal autopsies, malignant disease was discovered in 19 cases. The malignant diseases are discussed as to their primary sites and histologic types, age groups in which they occurred, conditions with which they may have been associated, symptoms and signs which in some cases may have warned of malignant disease, and supposed reasons why the malignant diseases were not recognized while the deceased were still alive. It was found that undetected malignant diseases occur mainly in the elderly, that chronic renal disease with scarred kidneys and cirrhosis of the liver may be predisposing conditions in cancer development, and that malignant disease in the aged may be undetected because of confusion with general weakness or because of small size and obviously slow growth of the tumor with lack of symptoms. PMID- 2917027 TI - A profile of women participants in five long distance winter sporting events. AB - Women have been entering long distance winter sports in increasing numbers in Alaska and other states and countries. Much publicity has been given to the success of some. The 1,100 mile Iditarod Sled Dog Race across Alaska has been won by a woman every year since 1985. The Minnesota Beargrease Sled Dog Marathon 500 mile race was won by a woman in 1988. But what of the experience of the average female entrant? This investigation sought to examine the circumstances of each of the women who competed in the Iditarod, Iditaski, Iditabike, Yukon Quest and Beargrease Marathon. Since December 1987, 79 questionnaires were mailed to all of the women participants (past and present) of these events and as of July 1988 the response rate was 58%. Examination of the findings in the areas of age ranges; training/competition miles; types, rates, self-treatment of injuries and protection from cold are reported. PMID- 2917028 TI - A pre-operative autologous blood donation programme in a small hospital. AB - The utilization and effectiveness of a pre-operative autologous blood donation programme were analyzed at a small, 40-bed, general hospital with subspecialization in orthopaedic surgery. Over a period of 8 months, 13 patients who were all to undergo total knee or hip replacement were evaluated. Twelve patients were found suitable and they donated in mean 1.9 units of blood. At discharge the patients who had donated blood pre-operatively had the same mean hemoglobin value as a comparable group of patients who only received blood from the ordinary blood bank service in spite of the total transfusion demand being the same in the two groups. The pre-donated blood covered 54% of the total demand of the group evaluated. The method is found especially applicable at small hospitals, where the administrative problems concerned with the method are easy to manage. PMID- 2917029 TI - Seal finger--diagnosis, prevention and treatment. AB - Seal finger is a well described disease as to symptoms and signs, but the etiology is still unknown. The disease may often be prevented and tetracycline has proved effective. PMID- 2917030 TI - Cigarette smoking in Cree Indian school children of the James Bay region. AB - A survey of cigarette smoking habits of Cree Indian school children in the James Bay region of northern Quebec was carried out. Out of 689 questionnaires completed by students in grades 6 through Secondary V (approximately ages 11 through 18), 13.2% were nonsmokers, 35.4% were exsmokers, and 51.4% were current smokers. 65% of the smokers were daily smokers and they averaged 7 cigarettes per day. Factors positively associated with being a current smoker were age, female sex, having a mother who smoked, and having a best friend who smoked. PMID- 2917031 TI - Teaching and funding nutrition instruction in family practice education. AB - Nutrition instruction is accepted as an important element of physician education, but is often not a formal part of medical school or residency training. Personnel and funding are often cited as the major factors that limit nutrition instruction. Because family medicine residency programs have been in the forefront of nutrition instruction, a nationwide survey of these programs was conducted to examine the nature, staffing, and funding mechanisms for nutrition education. Results of the 1986 survey reported in this study indicate that registered dietitians were available to 89% of the programs in the United States and are supported by a combination of funding sources. The implications of these findings are discussed. PMID- 2917032 TI - Physicians' and medical students' knowledge of nutrition. AB - A study was conducted to assess the knowledge of nutrition of 184 family practitioners and general internists and 24 first- and second-year medical students before they had received medical school instruction in clinical nutrition. Overall, the physicians answered 69.2% of the questions correctly, a significantly better score than that of the medical students (62.5%, p = .0065). The physicians scored better on topics that have been the most heavily researched (such as diet and coronary heart disease) and worse on less heavily investigated topics (such as diet and cancer, iron absorption). There was no significant difference in overall knowledge in terms of gender or practice. However, a significant negative correlation was found between the number of years since graduation from medical school and respondents' knowledge about nutrition. PMID- 2917033 TI - Academic medicine's changing covenant with society. AB - The traditional and mutually accepted covenant between academic medicine and society had its origin in trust and was based on the premise that academic medicine's programs and commitments were in society's best interests, thus justifying generous support and the privilege of self-regulation. In contemporary times, this mutually supportive covenant is encountering substantial distress. The most noteworthy threats to the traditional covenant are the changing values and erosion of trust emanating from the competition model of delivering and paying for medical services. A creditable response to society's needs and expectations can be best undertaken by establishing a national agenda in academic medicine that places a high priority on health services research and the scientific analysis of our entire health care system. What is needed now is the institutionalization of health services research through expansion of the cadre of health service researchers, while providing a broader emphasis on academic rewards and recognition for initiatives in this critically needed area of investigation. PMID- 2917034 TI - Nursing education and practice. AB - Three issues directly influence the relationship between nurses and physicians: the nature of nursing practice, the education of registered nurses, and the American Medical Association (AMA) proposal for registered care technicians. Many conflicts among nurses, physicians, and health care administrators result from nurses' defining their practice in terms of their patients' needs, and nurses may differ from other health care professionals in interpreting those needs. Nursing education programs--in hospital schools of nursing, community colleges, and baccalaureate colleges--should focus their programs and objectives so as to prepare their graduates for different health care settings. For example, an associate degree program would emphasize preparation for home health care, long term care, or acute care. The AMA proposal to create a new nursing category- registered care technologist--complicates rather than helps the relationship between physicians and nurses and confuses the issues of providing patient care. Suggestions are offered for alleviating the nursing shortage and resolving much of the continuing conflict between nurses and physicians. PMID- 2917035 TI - Enhancing attention to prevention: a new strategy. PMID- 2917036 TI - The discovery of the aged in the Third World. PMID- 2917037 TI - Rural health care: some accomplishments, much to be done. PMID- 2917038 TI - Congress challenges medical schools on progress in minority representation. PMID- 2917039 TI - Coming to terms with the nursing shortage--asserting the role and initiatives of academic health centers. PMID- 2917040 TI - Nutrition education. PMID- 2917042 TI - Cultural literacy. PMID- 2917041 TI - Use of animals. PMID- 2917043 TI - A second survey of graduates of a traditionally black college of medicine. AB - To update and expand upon its 1975-76 survey of 729 graduates of seven classes, Howard University College of Medicine (HUCM) conducted a longer survey in 1985-86 of 1,985 graduates spanning 49 classes. Replies of the 728 respondents to the second survey confirm that HUCM's predominantly black alumni were continuing to provide patient care to a substantial number of poor blacks in urban areas. Fifty six percent of all HUCM alumni were in primary care, compared with 46% of all alumni of U.S. medical schools who were in primary care. New findings included concerns about malpractice suits and physician impairment. Regarding physician supply in their own communities, 53% of respondents believed that there were too many physicians overall, but 63% believed there were too few black physicians. For the 1940-1969 graduates, loans financed 10% of their medical education, and indebtedness influenced the types of practice chosen by 4%; comparable figures for the 1970-1980 graduates were 25% and 11%. PMID- 2917044 TI - Effect of nutrition education on nutrition counseling practices of family physicians. AB - The effects of completing a comprehensive nutrition curriculum on the nutrition counseling practices of family physicians trained at the University of Manitoba were investigated by sending a questionnaire to a group of these physicians who had completed the nutrition curriculum and a group that had not. The 48 responding family practice residency-trained physicians who had completed the nutrition curriculum, and the 41 responding hospital-trained physicians who had not, reported counseling practices that were not significantly different (p greater than .05). Implications and recommendations for future teaching of nutrition counseling skills to physicians during residency training are presented. PMID- 2917045 TI - Monoclonal antibodies: production and application. PMID- 2917046 TI - Enhanced proliferating activity of cultured smooth muscle cells from SHR. AB - In order to explore the cellular mechanisms responsible for the vascular abnormalities observed in hypertension, smooth muscle cells (SMC) were cultured after enzymatic digestion of aortas from both normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). These cultures were performed in the presence of fetal calf serum (FCS) and stimulated by vasoactive agents (angiotension II, serotonin, bradykinin). Growth rate was determined by cell counting and measurement of nuclear-tritiated thymidine incorporation and phospholipase C (PLC) activation by measurement of 3h-inositol mono-, di-, tri-, and tetra-phosphates formed from preincorporated 3h-myo-inositol. Cells from SHR proliferate more actively than control ones in the presence of 10% FCS but don't significantly differ at lower concentrations. In the presence of 5% FCS angiotensin II (10(-7) mol/L), 5-HT (10(-6) mol/L) and bradykinin (10(-6) mol/L) enhance cell proliferation and their effect is more important in cultures from SHR. The phospholipase C activation induced by these drugs was also more important in these SHR cultures than in control ones. The PLC hyperreactivity observed in SHR cells may therefore be involved in their enhanced proliferating activity evidenced in culture and in the vascular abnormalities described in vivo. PMID- 2917047 TI - Different determinants of left ventricular filling in normotensive subjects and essential hypertensive patients. AB - The aim of the study was to evaluate the relationships between left ventricular (LV) filling and age, heart rate (HR), blood pressure (BP), and LV mass in three groups of subjects with different casual blood pressure. Twenty normotensive subjects (NT: age 39.2 +/- 7.2; BP 121.6 +/- 11.3/77.7 +/- 7.5 mm Hg), 16 borderline hypertensives (BH: age 38.6 +/- 9.2; BP 138.2 +/- 11.6/91.7 +/- 9.4 mm Hg), and 20 essential hypertensives (EH: age 44.5 +/- 8.3; BP 165.7 +/- 14.8/107.6 +/- 11.4 mm Hg) underwent 2D Echo evaluation and PW Doppler measurements of transmitral blood flow velocity. In NT, the Doppler indexes of LV filling showed significant correlations only with age and heart rate (age v E peak: r = .68 P less than .001; v A peak: r = .45, P less than .05; v A/E: r = .78, P less than .001. Heart rate v A peak: r = .78, P less than .001, v A/E: r = .74, P less than .001, respectively). Similar but weaker relationships were observed in BH. On the contrary, EH showed no significant correlations with age or heart rate, but with both systolic blood pressure (SBP), diastolic blood pressure (DBP), and LV mass (SBP v A peak: r = .49, P less than .05; v A/E: r = .68, P less than .001; DBP v E peak: r = 44, P less than .05; v A/E: r = .58, P less than .01. Left ventricular mass v E peak: r = .45, P less than .05; v A/E: r = .51, P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2917048 TI - Dipyridamole-echocardiography test in essential hypertensives with chest pain and angiographically normal coronary arteries. AB - Microvascular angina--chest pain syndrome in the presence of angiographically normal epicardial coronary arteries and reduced flow reserve--has been described in patients with essential hypertension (EH) and linked to the development of left ventricular hypertrophy (LVH). We performed a dipyridamole-echocardiography test (DET: 2D-echo and 12 lead ECG monitoring with dipyridamole infusion, up to 0.84 mg/kg over ten minutes) in 28 essential hypertensives meeting the following inclusion criteria: (1) history of chest pain; (2) angiographically normal coronary arteries; (3) normal resting regional and global left ventricular function. A group of 12 (age- and sex-matched) normotensives with the same inclusion criteria, as well as with negative exercise stress test, was also evaluated. During DET, none of the essential hypertensives or the control group developed a regional dyssynergy of contraction. Fifteen essential hypertensives and two in the control group had a diagnostic (greater than 0.1 mV from baseline) ST segment depression on ECG tracing (54 v 17%, P less than .01); 16 essential hypertensives and two in the control group had chest pain (57 v 17%, P less than .01). None of the control group and nine of the essential hypertensives had echocardiographically assessed LVH. In the essential hypertensive group ventricular hypertrophy was present in seven of 20 patients with and in two of eight patients without dipyridamole induced chest pain and/or ST segment depression (35% v 25%, P = NS). In conclusion, essential hypertensive patients with chest pain and angiographically normal coronary arteries frequently show echocardiographically silent angina and/or ST segment depression during DET.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2917049 TI - Critical comments on recent literature. The J curve and other problems with therapy. PMID- 2917050 TI - Left ventricular mass in normotensive subjects. Importance of blood pressure response to activity. AB - Recent works have shown the importance of blood pressure (BP) response to exercise or to daily activity as determinants of hypertensive cardiac hypertrophy. We have tested the relationship between BP and left ventricular (LV) mass in 23 normotensive young adults (mean age 25 +/- 5) with normotensive parents. Blood pressure was measured at rest, at the end of maximal exercise test, and during 24-hour ambulatory monitoring during daily routine. Left ventricular mass was assessed with M-mode echocardiography. We found a closer relationship between LV mass with BP when measuring during activity (average day time BP and end exercise BP) than with rest BP (rest BP and average nighttime BP). Multiple regression analysis indicates an independent association of LV mass with both average day time and end exercise systolic blood pressure. Thus, we conclude that these two ways of assessing "activity" BP may be more complementary than opposing. Ambulatory BP monitoring appreciates the reactions to daily stresses and the exercise test measures the response to physical activity. PMID- 2917051 TI - Effect of glucocorticoid deficiency on arterial pressure in conscious spontaneously hypertensive rats. AB - The effect of selective glucocorticoid or mineralocorticoid deficiency upon arterial pressure was evaluated in unanesthetized adult spontaneously hypertensive rats (SHR). Adrenalectomized SHR were replaced with 6 micrograms/24 h aldosterone (ALDO), 10 microgram/24 h dexamethasone (DEX), or both aldosterone and dexamethasone (ALDO + DEX) by IP osmotic mini-pumps. These were compared to sham-operated SHR (SHAM) and adrenalectomized SHR given no steroid replacement (ADX). Drinking fluid for all groups was 1% NaCl + 2.5% glucose. Six days after adrenalectomy, intra-arterial mean arterial pressure (MAP) fell from 174 +/- 2 to 149 +/- 6 mm Hg in ALDO (n = 8, P less than .01) and from 179 +/- 4 to 125 +/- 4 in ADX (n = 6, P less than .01). In contrast, MAP rose in SHAM from 171 +/- 4 to 179 +/- 5 mm Hg (n = 7, P less than .01), in ALDO + DEX from 161 +/- 3 to 184 +/- 4 mm Hg (n = 7, P less than .01), and in DEX from 162 +/- 2 to 181 +/- 4 mm Hg (n = 7, P less than .01). The results indicate that when diet salt intake is high, glucocorticoid action is necessary for the full expression of hypertension in adult SHR. PMID- 2917052 TI - Periarthrosis of the shoulder associated with diabetes mellitus. AB - Among the protean complications of diabetes mellitus are contractures of the joints and periarticular soft tissue. These complications have not been well described in the literature. This syndrome of "limited joint mobility," has been reported as occurring in young, insulin-dependent diabetics, with primary involvement of the small joints of the hands. In older diabetics, similar changes have been described with additional contractures developing in the large joints of the upper extremities. This report presents clinical findings occurring in five older diabetics with primary contractures of the shoulder. Theoretical considerations are also discussed regarding the neurophysiology of this entity as well as the current treatment options. PMID- 2917053 TI - A prospective study of peripheral nerve lesions occurring in traumatic brain injured patients. AB - The purpose of this study was to determine the frequency and severity of peripheral nerve lesions occurring in patients with traumatic brain injury. A prospective study of 132 patients was conducted. Patients fulfilling research criteria (flaccidity, areflexia, abnormal motor patterns) underwent neurodiagnostic examination. Fifteen electromyograph/NCV studies were performed, yielding positive findings in 13 patients (10%); 3 patients were found to have preventable lesions. Many patients had permanent impairment or attendant complications from the peripheral nerve injury that adversely affected eventual recovery. PMID- 2917054 TI - Over fifty support group for patients in a rehabilitation hospital. Commentary. AB - The psychosocial needs of newly disabled 50- to 85-year-old individuals are often neglected in rehabilitation. The Rehabilitation Hospital of the Medical College of Ohio has addressed these needs with the establishment of an over 50 support group. Topics chosen by the group focused on common fears and concerns. The group has been valuable in offering opportunities for peer reinforcement, problem solving, and ventilation of feelings in a safe and supportive setting which had not before existed. PMID- 2917055 TI - Research in physical medicine and rehabilitation. I. How to ask the question. AB - A predictable pattern in research efforts is seen in 28 academic centers in physical medicine and rehabilitation. They consist of at least one technician and one small research room (220 square feet), with an additional small room (280 square feet), and 1/4 technician for every MD or PhD in the department (r = 0.72). Persons who are not active researchers with external funding must first define the research question in order to develop fundable research proposals. Clinical research is a process that starts from the clinical situation, leads to formulation and answering of the question, and eventually results in integration back into clinical practice. There are many reasons for posing a clinical research question and each results in a different type of question. Asking the right question is the most important part of research, as how the problem is stated determines what data is to be collected, the analysis to be done, and what kind of conclusions can be drawn. A strong research study addresses questions that are clearly spelled out and leads to conclusions that are within the limits of the experimental design and the availability, reliability, and validity of the data. Complex design and analysis do not make a study better if the question itself is not well formulated. It is not as important to know how to answer the question as it is to know how to ask the question. If the initial question is incomplete or incorrect, the rest of the research is at best irrelevant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2917056 TI - Lower extremity manifestations of spasticity in chronic spinal cord injury. AB - The prevalence of various manifestations of spasticity from questionnaire responses and from clinical examination of chronic spinal cord injured patients is reported. Extensor spasms, flexor withdrawal spasms, and clonus were reported by most subjects. Those with incomplete lesions reported more interference with activities, more pain, and less functional usefulness, than did those with complete lesions. Extensor spasms were reported to interfere more with transfers, whereas flexor withdrawal spasms were reported to be more frequent at night and to interfere more with sleep. Increased muscle tone was observed more often in extensor than in flexor muscles. Those with incomplete lesions had more hypertonus and more limited passive joint movements than did those with complete lesions. Flexor withdrawal reactions and extensor spasms were also more pronounced in those with incomplete lesions, particularly those with Frankel grade C lesions. PMID- 2917057 TI - Excellence in rehabilitation through research. Commentary. PMID- 2917058 TI - Normative model for cold pressor test. AB - The cold pressor test elicits an emotional/motivational pain experience from the immersion of a limb in cold water. It has been widely used to evaluate (experimental and chronic) pain. However, normative models for quantification and comparison for pain tolerance have not previously been established. This study developed a normative mathematical model for pain tolerance using the cold pressor test with over 600 subjects. Norms for age, sex, and ethnic group were calculated. In addition, chronic pain patients were compared with pain-free patients to determine normative differences in response. The results indicate that at any given age Anglo-Saxon males have the longest tolerance time followed by non-Anglo-Saxon males, Anglo-Saxon females, and finally non-Anglo-Saxon females. There is a consistent decrease in tolerance time as the male age increases and minimal change in tolerance time as the female age increases. Chronic pain patients exhibited the same type of pain response pattern as healthy volunteers when corrected for age, sex, and ethnocultural subgroup. PMID- 2917059 TI - [The promille limit and reduced responsibility]. AB - In a review the author agrees with the German Federal Court's judgement of 9.8.88 (see Blutalkohol 25,403). He deals with the relation between physiological and psychological circumstantial evidences (blood-alcohol-concentration and condition of personality in the time of violation) and with their reference to the ascertainment of reduced responsibility. In accordance with the Federal Court he states that within the necessary total assessment the importance of blood-alcohol concentration is the lower the more the BAC-level figured out is remote from the probable BAC in the time of violation because of the long period of time between. He concludes that the Federal Court was successful in it's attempt to draw the juridical arguments near to those of forensic medicine. PMID- 2917060 TI - Evidential breath ethanol analyzers, accuracy and sensitivity to breath acetone. AB - The purposes of this study included the examination of the relative accuracy of a number of evidential breath analyzers available in the United States, the sensitivity of ethanol breath analyzers to simulated breath acetone and the generation and subsequent interference created by endogenous acetone. This study used both laboratory simulation and human ethanol testing as well as a systematic examination of the sensitivity of various ethanol breath test instruments to both endogenous and simulated breath acetone. The results suggest that when evidential breath ethanol testers are administered in a uniform fashion, consistent and reliable results occur. Further, endogenous and simulated breath acetone can effect infrared ethanol breath testers but at levels in the case of endogenous acetone, in a non-significant fashion. Simulated breath acetone, consistent with other research produced selective interference on evaluation of breath instruments. The instruments utilizing wavelength 3.4 microns infrared bands were affected the greatest. Endogenous breath and blood acetone was demonstrated in a non-diabetic. The resulting breath acetone levels did produce mimicked ethanol levels on all single wavelength (3.4 microns range) instruments. Nine micron IR range instruments and the Breathalyzer 900 which utilizes a wet chemical procedure were unaffected by endogenous acetone. Those instruments equipped with acetone detectors, found in certain instruments, did not identify endogenously produced acetone. PMID- 2917061 TI - [Elimination properties of the congener n-propanol]. AB - Intravenous injections of n-propanol (25 mg, 50 mg, 100 mg, 200 mg, 300 mg) provoke blood concentration curves having exponential shapes of dose dependent rate constants after a sufficiently long time (2 min). They have to be seen therefore as a result of a non-linear elimination process controlled by a Michaelis-Menten-kinetic. Using the Lineweaver-Burk-method the characteristic data of metabolism are determined, namely the maximal velocity of metabolizing beta PrOHmax as 2.5 mg/l min and the Michaelis-Menten-constant as 10 mg/l. An increase of the ethanol exposition causes a prolongation of the mean residence time of n-propanol in the body. This phenomenon is to be interpreted as the result of an inhibition of the n-propanol metabolism by ethanol. The inhibition constant KPrOHEtOH concerned with this process is determined experimentally and has a value of 0.1%. PMID- 2917062 TI - [Causes and incidence of traffic accidents caused by precipitous disorders of consciousness and illnesses of drivers. A one year study in Upper Austria and Salzburg]. AB - It was attempted to make a survey of all traffic accidents due to sudden disturbances of health on behalf of drivers, being supported by the police of Upper Austria and Salzburg. Only 26 out of a total amount of 53.530 road accidents were made known but the cooperation with the police did not always seem to work too well. Only in the province of Salzburg did the number of these accidents correspond with the expected frequencies of 1.3%. Most of the drivers were internally sick, cardiovascular diseases prevailing. The danger of epilepsy is generally overestimated, that of diabetes and other internal diseases rather underrated. People in general good health were also seen causing accidents due to nausea. In such cases self-endangering is twice as common as the exposure of others to danger. In the majority of the incidents only damage to property resulted. In addition it became apparent, that accidents with damage to people occurred more often in the city than in rural areas, whereas fatalities and severe injuries were more common in the country than in cities. PMID- 2917063 TI - New concepts in hair replacement. PMID- 2917064 TI - Surgical access for clivus chordoma. The University of California, San Francisco, experience. AB - Surgical approaches to clivus chordoma are discussed. The approaches described in this article have been used in an attempt to minimize morbidity while maximizing exposure. The transseptal-transsphenoidal approach is appropriate for biopsy or for subtotal removal of small midline lesions of the upper (retrosellar) clivus only. The radical pterygomaxillotomy approach is used for gaining access to chordomas of the upper half of the clivus, with or without lateral extension. Removal of the lateral, posterior, and (if necessary) medial walls of the maxillary sinus is followed by resection of most of the contents of the pterygopalatine fossa. The pterygoid plates are then removed with a drill. The sphenoid sinus and upper clivus are then exposed for tumor removal. For more inferior lesions, we have modified the transoral-transpharyngeal approach by creating an inferiorly based posterior pharyngeal flap, which increases exposure of the clivus, particularly laterally. This flap can be extended laterally for paraclival extension. This approach allows removal of the lateral clivus as far laterally as the hypoglossal canal, with no dissection of tongue, mandible, lip, or cervical soft tissues. PMID- 2917065 TI - The transfacial approach for combined anterior craniofacial tumor ablation. AB - The transfacial approach to the anterior cranial fossa for tumor removal provides for excellent surgical exposure, improved postoperative appearance, and a minimum of complications. The technique is different from previously reported combined craniofacial ablative procedures in that the head and neck surgeon and the neurosurgeon approach the anterior fossa mass through the same facial incision, thus avoiding the need for a separate craniotomy incision. The formation of a vascularized nasofrontal bone flap allows for better wound healing regardless of preoperative and postoperative radiotherapy and/or chemotherapy. This report presents 42 cases in which the transfacial approach was exclusively used in a combined manner to remove nasal, paranasal sinus, and nasopharyngeal neoplasms. The transfacial technique offers a significant advantage over previously described approaches to the anterior skull base. PMID- 2917066 TI - Anterior craniofacial resection for ethmoid and nasal cancer with free flap reconstruction. AB - Two surgical approaches were used for nasal and ethmoid cancers involving the anterior skull base. A craniofacial operation with the assistance of a neurosurgeon was employed when the cribriform plate was infiltrated. A frontofacial operation through the frontal sinus was preferred when the cribriform plate was radiologically intact. Thirty patients underwent radical surgery with a minimum three-year follow-up. Thirteen of 16 patients with adenocarcinoma survived. Since 1980, nine patients have had their surgical defects repaired with a revascularized tensor fascia lata muscle and skin flap. The flap is tailored to support the cranial contents, provide muscle bulk for the orbitomaxillectomy cavity, and provide skin for the face, nasal, and palatal surfaces. There were two free flap failures. PMID- 2917067 TI - Approach to the pterygomaxillary space and posterior part of the tongue by lateral stair-step mandibulotomy. AB - Fifteen patients underwent surgery for retromandibular parotid, pharyngeal, or posterior tongue tumors. Surgical approach to the pterygomaxillary fossa, parapharyngeal space, and posterior tongue was performed by external cervical incision and lateral stair-step mandibulotomy. After resection of the tumors, the mandibular segments were replaced and secured with miniplates. The plates were removed after six weeks whenever postoperative radiation therapy was planned. By reflecting the ascending ramus, this method provides excellent exposure of the concerned areas. It makes unnecessary both incision of the lower lip and intermaxillary fixation with arch bars, thus allowing a quick resumption of oral feeding. A review of 15 patients demonstrated satisfactory results for mandibular function and morphologic appearance, with minimal complications. PMID- 2917068 TI - Prognostic factors in patients dying of well-differentiated thyroid cancer. AB - While some well-differentiated cancers of the thyroid gland are unusually aggressive, most have a more benign clinical behavior, making it difficult to evaluate factors possibly influencing patient survival such as initial surgical treatment. By studying 135 patients who received their initial surgical therapy at our institution, we have defined the prognostically significant factors. Sixteen patients (11.9%) died of disease during a ten- to 20-year follow-up period. Significant factors associated with death from disease were aged 40 years or older, primary lesion size of 2.5 cm or greater, presence of invasive characteristics, and presence of distant metastases. We recommend total thyroidectomy and postoperative sodium iodide I 131 therapy in patients 40 years of age or older, while suggesting a less aggressive approach may be appropriate in the younger patients. PMID- 2917069 TI - Recent experience with reconstructive surgery following major glossectomy. AB - In an attempt to monitor the impact of new reconstructive procedures and shifting interest away from routine preoperative radiotherapy, we have reviewed the 81 patients undergoing major glossectomy and reconstruction (MGR) at the Royal Marsden Hospital, London and Surrey, England, between 1975 and 1987. While there were four marginal and 13 major reconstructive failures, 11 of the latter were successfully managed with an alternative flap, thus providing a prompt and effective palliation for most of these patients. An evolution in our choice of reconstructive procedures as well as a recent trend toward using MGR as a primary therapeutic modality were noted. Data relating to speech following reconstruction and diet rehabilitation were encouraging, particularly with the use of the latissimus dorsi flap. Survival following MGR, however, was dismal due to early local and regional recurrence. PMID- 2917070 TI - Secondary tracheoesophageal puncture for voice rehabilitation after laryngectomy. AB - Since the introduction of the tracheoesophageal puncture technique for restoration of voice in 1980, 125 secondary punctures have been performed in 117 patients at the Cleveland Clinic Foundation. Preoperative evaluation, pharyngeal preparation, and their relation to final speech results were reviewed retrospectively. Critical factors in the rehabilitation of these patients are discussed based on our experience and a review of the literature. PMID- 2917071 TI - Tracheoesophageal puncture for voice restoration after extended laryngopharyngectomy. AB - Tracheoesophageal puncture was performed in ten of our patients undergoing extended laryngopharyngectomy. Three fistulas were allowed to close, and two patients were dissatisfied with their results, which allowed for an overall 50% success rate in this subgroup. The resultant voice was objectively compared with similar groups of patients undergoing primary and secondary tracheoesophageal puncture after standard laryngectomy. There was no significant difference in maximum phonation time, average speaking intensity, and average fundamental frequency between these groups. However, the maximum intensity and average intensity were significantly lower for the flap group. Our results indicate that tracheoesophageal puncture should be attempted in patients undergoing the extended procedure, notwithstanding a lower expected success rate. PMID- 2917072 TI - Fate of skin element of pectoralis major flap in intraoral reconstruction. AB - A skin island carried by pectoralis major muscle has been used to reconstruct an intraoral defect created after resection of a tumor. To our knowledge, what happens to the skin after its mobilization from the chest wall into the mouth has not been documented. To answer this, a wedge biopsy of the intraoral skin island on the pectoralis muscle was performed in 14 patients under local anesthesia. The skin biopsy specimen was subjected to scanning electron microscopic and histologic examination. The interval between the reconstructive surgery and the biopsy ranged from ten to 66 months (mean, 32 months). The results revealed desquamation of the epidermis and loss of appendages. The degree of desquamation was maximal when the skin island was used to replace the whole of the floor of the mouth and least when it was used for the lateral portion. PMID- 2917073 TI - Superior and transantral orbital decompression procedures. Effects on increased intraorbital pressure and orbital dynamics. AB - Eight superior and eight transantral decompressions were performed in 16 fresh cadaver orbits in which intraorbital pressure was experimentally increased by adding 12 mL of volume to an intraorbital balloon. Each decompression yielded a mean pressure decrease of 225 mm Hg (85% of the total) in experimentally induced intraorbital pressure. The maximal pressure decrease occurred after the removal of the first complete orbital wall. However, incision of the periorbita was most effective in achieving globe recession and a decrease in exophthalmos. Although the steps of the superior and transantral decompression techniques are not comparable, there was no statistically significant difference between the total net pressure decreases achieved. PMID- 2917074 TI - Desmoplastic melanoma. Histologic correlation with behavior and treatment. AB - Desmoplastic (neurotrophic) melanoma is a histologic variant of cutaneous melanoma that has a distinct clinical behavior. To better understand this behavior and to treat the disease more effectively, the medical records of 16 patients treated for this disease over a 12-year period were reviewed. Thirteen patients had head and neck lesions, the ear being a common site. The average thickness of the lesions was 5.75 mm. Six (46.2%) of 13 patients had local recurrence of disease. Only two patients (15.4%) developed regional node metastases. None of the patients with clinically NO desmoplastic melanoma were found to have positive nodes after elective neck dissection, regardless of the thickness of the primary lesion. Wide excision of the primary lesion with frozen section control of surgical margins and careful examination for the presence of perineural invasion is important in determining the extent of surgical resection. PMID- 2917075 TI - Chondromyxoid fibroma of the mastoid invading the occipital bone. AB - We describe a case of chondromyxoid fibroma of the mastoid bone extending along the occipital bone in a 48-year-old man. The presence of this tumor was heralded solely by aural fullness caused by otitis media with effusion. The tumor arose from the mastoid cavity, eroding the entire petrous portion, and invading the foramen magnum and jugular foramen. The occurrence of this tumor is exceedingly rare, and, to our knowledge, this is only the second article in the literature that describes a chondromyxoid fibroma of the mastoid region. The clinical appearance of this tumor and its light- and electron-microscopic findings are presented with reference to other articles. PMID- 2917076 TI - Convulsions secondary to hyponatremia associated with labyrinthectomy. AB - A case of convulsions occurring 48 hours following transcanal labyrinthectomy for Meniere's disease in a 76-year-old woman is described to illustrate the unexpected onset of severe hyponatremia after surgery. This syndrome is believed to be produced by inappropriately increased levels of antidiuretic hormone in healthy women without any associated medical condition. To prevent severe central nervous system damage and death, early recognition and appropriate correction of this cation deficiency is necessary. PMID- 2917077 TI - Pathologic quiz case 2. Kaposi's sarcoma (KS) of the oral cavity. PMID- 2917078 TI - Pathologic quiz case 1. Amyloidosis of the larynx. PMID- 2917079 TI - Gentamicin therapy in tympanostomy. PMID- 2917080 TI - Recurrent otitis externa. PMID- 2917081 TI - Specialisation in dentistry. PMID- 2917082 TI - 'The control of cross-infection in dentistry'. PMID- 2917083 TI - 'Why not the NHS?'. PMID- 2917084 TI - European Prosthodontic Association. PMID- 2917085 TI - Local anaesthetics in pregnancy. PMID- 2917086 TI - Contract confidence trick? PMID- 2917087 TI - Computerised matching for house officer posts. PMID- 2917088 TI - Cutting Korners. PMID- 2917089 TI - Presentation and antimicrobial treatment of acute orofacial infections in general dental practice. AB - Information on the presentation of orofacial infections and the use of antimicrobial agents in general dental practice in the United Kingdom was obtained using a postal questionnaire. Six hundred dentists were randomly selected and a total of 340 replies were received, giving a response rate of 57%. The dental practitioners estimated that acute infection was present in only a minority (approximately 5%) of patients. A total of seven different antibiotics were prescribed, in a variety of regimens, for the treatment of bacterial infection. However, the majority of dentists (46-62%) preferred a 5-day course of penicillin (250 mg, qid) for bacterial conditions other than acute ulcerative gingivitis, for which most practitioners (89%) prescribed 3 days of metronidazole (200 mg, tid). Nystatin was the most frequently selected anticandidal agent and topical acyclovir the most popular therapy for Herpes simplex infection. PMID- 2917090 TI - Multiple idiopathic internal resorption. AB - A very rare case is presented of multiple idiopathic internal resorption, which progressively involved all the mandibular incisor teeth. PMID- 2917091 TI - Descriptive statistics. AB - The importance of a knowledge of statistical methods in relation to most aspects of dentistry is discussed. Definitions of terms used in descriptive statistical techniques are provided, together with a review of the techniques themselves. PMID- 2917092 TI - Keeping up-to-date with tooth notation. AB - Methods of tooth notation have evolved over the years and there is now an increasing desirability for a system which offers the maximum in precision, clarity and compatibility with typing and computing requirements. A review of the many available methods leads to the FDI two-digit system as being highly appropriate for today's needs. This system is being adopted increasingly, worldwide. PMID- 2917093 TI - Oral surgery: staying healthy. AB - As one of the caring professions, dentistry has always concerned itself with the welfare of its patients, tending to their aches and pains, their needs and demands, and treating and preventing those diseases that occur in and around the mouth; we offer our skills and expertise to improve the quality of life of others. Unfortunately, nowadays the provision of such a service to our patients carries with it risks that were unknown 25 years ago. Once, when antibiotics were effective against syphilis and tuberculosis, dentistry carried little risk to the health of the practitioner and his staff. With the emergence of diseases that pose severe threats to both dentist and staff, our concept of a caring profession must now be broadened to include not only caring for the patient, but also caring for the health and welfare of the dentist who provides the treatment and for the staff who support him in this provision. PMID- 2917094 TI - Pitfalls and limitations in the use of impedance cardiography. PMID- 2917095 TI - Quantitative phase analysis in the assessment of coronary artery disease. AB - The phase image in radionuclide ventriculography shows the timing of ventricular contraction and is valuable in the detection of abnormalities induced by coronary artery disease. The image is usually interpreted subjectively, and in the present study a histogram of left ventricular phase values was used to make interpretation more objective. The left ventricular ejection fraction and the standard deviation, skewness, and kurtosis of the phase histogram were measured at rest, during isometric exercise, and during the final two stages of maximal dynamic exercise in 25 controls and 27 patients with coronary artery disease without previous infarction. The ejection fraction and the standard deviation of the phase had the same predictive accuracy for the presence of disease when measured during the penultimate stage of dynamic exercise (89%) as during the final stage, but their accuracy was lower during maximal exercise (77%) because of motion artefact at high exercise levels. Skewness and kurtosis of the histogram were of no value for the detection of disease, and isometric exercise was of only limited value. It is concluded that the phase histogram provides an objective measurement of the synchronicity of left ventricular contraction and can increase sensitivity for the detection of abnormality. Data should be acquired at all stages of dynamic exercise, and the penultimate stage should be used if there is any doubt about the validity of the final stage. PMID- 2917096 TI - Restrictive cardiomyopathy and constrictive pericarditis: non-invasive distinction by digitised M mode echocardiography. AB - It is difficult to distinguish between restrictive cardiomyopathy and constrictive pericarditis on the basis of clinical findings and simple investigation. Cardiac catheterisation has been the reference standard for diagnosis but even this does not always permit an accurate distinction. A Summagraphics digitiser and Prime 750 computer system were used to digitise the echocardiograms of 15 patients with restrictive cardiomyopathy, 10 with constrictive pericarditis and a group of 20 age and sex matched normal subjects of similar age and sex distribution. Compared with controls, patients with restrictive cardiomyopathy showed a significant reduction in the following variables (a) decreased fractional shortening, (b) decreased peak left ventricular filling and emptying rates, (c) decreased percentage posterior wall thickening, and (d) decreased peak left ventricular posterior wall thickening and thinning rates. Whereas patients with constrictive pericarditis only had significantly reduced peak left ventricular filling and posterior wall thinning rates and significantly increased posterior wall thinning rate. When patients with restrictive cardiomyopathy were compared with those with constrictive pericarditis the significant differences were: (a) decreased peak left ventricular emptying rate, (b) decreased percentage posterior wall thickening, and (c) decreased peak left ventricular posterior wall thickening and thinning rates. Digitisation of M mode echocardiograms, with particular attention to posterior wall function, may be a useful adjunct to cardiac catheterisation in distinguishing restrictive cardiomyopathy from constrictive pericarditis. PMID- 2917097 TI - Electrode catheter ablation for ventricular tachycardia: efficacy of a single cathodal shock. AB - Electrode catheter ablation was used to treat 11 distinct types of sustained ventricular tachycardias in eight patients. Rigid electrophysiological criteria were used to identify five left and five right ventricular arrhythmogenic sites; one of them gave rise to tachycardia with two distinct configurations. A single R wave-synchronised 250 or 150 J cathodal shock was delivered at each site. One patient had mildly symptomatic episodes of sustained ventricular tachycardia during the first four days after the shock--there were no other complications. At discharge none of the patients was taking antiarrhythmic drugs. They were followed for 8-20 months (mean 14). Ablation abolished five of the 11 ventricular tachycardias. There was no recurrence in three of the eight patients. In two patients identical ventricular tachycardias recurred because the identification of the arrhythmogenic site was incorrect. PMID- 2917098 TI - Physiological importance of different atrioventricular intervals to improved exercise performance in patients with dual chamber pacemakers. AB - To determine the importance of different atrioventricular intervals during exercise in patients with dual chamber pacemakers, seven patients with complete heart block and sinus rhythm were exercised in different pacing modes and atrioventricular intervals: (a) ventricular inhibited (VVI) pacing with no synchronous atrial augmentation or rate responsiveness; (b) atrial synchronous ventricular or DDD pacing with a short mean (SD) atrioventricular interval of 66 (4) ms; and (c) DDD pacing with a long atrioventricular interval of 168 (12) ms. Pacing with a short or long atrioventricular interval gave similar maximum heart rates, oxygen uptake at the anaerobic threshold, end tidal pressure of carbon dioxide or oxygen pulse (a measure of stroke volume). Pacing with either a short or long atrioventricular interval produced a significantly higher oxygen consumption and anaerobic threshold and less lactate production than VVI pacing. During exercise a short atrioventricular interval does not provide a better cardiopulmonary performance than a long atrioventricular interval. PMID- 2917099 TI - Abnormal cardiac signs after Fontan type of operation: indicators of residua and sequelae. AB - Among 74 survivors of the Fontan type of operation abnormal cardiac signs were detected in 46 (62%) at postoperative examination. The findings were analysed in relation to the state of the cardiovascular system of these patients. Cyanosis was present in 10 (13.5%) patients. The causes of cyanosis included residual interatrial shunt (six patients), acquired pulmonary arteriovenous fistulas (three patients) and acquired systemic-to-pulmonary vein communication (one patient). Signs of chronic fluid retention were detected in six (8%) patients. In four of them the fluid retention was related to conduit obstruction and in the remaining two it was secondary to severe subaortic stenosis in one and atrioventricular valvar regurgitation in the other. Organic heart murmurs were heard in 29 (39%) patients. The aetiologies of these murmurs were multiple. They included aortic valve regurgitation (eight patients), subaortic stenosis (seven patients), atrioventricular valvar regurgitation (five patients), pulmonary valve regurgitation (five patients), residual Blalock-Taussig shunt (two patients), residual ventricular septal defect (two patients), residual communication in the main pulmonary artery which had been ligated but not divided (one patient), and left ventricular to right atrial shunting (one patient). Cardiac rhythm disturbances of varying aetiology were noted in 23 (31.1%) patients. Sixteen (21%) had supraventricular arrhythmias and seven (9.5%) had conduction abnormalities. The present review suggests that among survivors of the Fontan type of operation abnormal cardiac signs are indicators of residua or sequelae or both of the native cardiovascular anomalies or surgical procedures. PMID- 2917100 TI - Advantages of colour flow imaging in the diagnosis of left ventricular pseudoaneurysm. AB - Eleven cases of left ventricular pseudoaneurysm in nine patients were studied by cross sectional echocardiography, conventional Doppler echocardiography, and colour flow imaging. In two patients recurrent pseudoaneurysms developed after cardiac surgery, three had acute rupture after myocardial infarction, two were the result of stab wounds, one was a late rupture of a true left ventricular aneurysm, one developed after surgical resection of a true left ventricular aneurysm, and two as a consequence of left ventricular venting. In all 11 cases the diagnosis was confirmed by angiographic or surgical information or both. The diagnosis was suspected clinically in only four cases. Cross sectional echocardiography alone confirmed the diagnosis in five cases. Neither pulsed wave Doppler nor continuous wave Doppler established the diagnosis when they were used without colour flow imaging in five and three cases respectively. In all 11 cases colour flow imaging showed flow in and out of the pericardial cavity at the defect site as well as the abnormal flow within the pseudoaneurysm. Subsequent use of pulsed Doppler showed a consistent "to and fro" flow pattern across the myocardial defect with characteristic respiratory variation of the peak systolic velocity. This unique intrapericardial flow pattern is diagnostic of a pseudoaneurysm. Colour flow imaging is a valuable addition to cross sectional and Doppler echocardiography, and is the best technique for detecting left ventricular pseudoaneurysms. PMID- 2917101 TI - Balloon dilatation of a stenosed bioprosthesis in the tricuspid valve position. AB - Percutaneous balloon dilatation of a stenosed Ionescu-Shiley bioprosthesis in the tricuspid valve position was performed twice in a 19 year old woman. On each occasion there was a considerable improvement in symptoms and haemodynamic function but the effect lasted for only a few months. When the valve was excised it showed no evidence of the previous balloon dilatations. PMID- 2917102 TI - Proceedings of the British Cardiac Society. Autumn meeting. London, 22 to 24 November 1988. Abstracts. PMID- 2917103 TI - Fatal haemopathological consequences of general anaesthesia. AB - A previously healthy 63-yr-old female died following an anaphylactoid response to anaesthesia with thiopentone and suxamethonium. Postmortem findings strongly suggested that disseminated intravascular coagulation played a significant role in her death. The local mechanism behind the reaction is unknown, but the formation of thiopentone-suxamethonium colloid aggregates during induction, may have led to "aggregate anaphylaxis". PMID- 2917104 TI - Acute gastric dilatation in an incarcerated hiatus hernia. AB - A case is reported of an unusual complication in which acute gastric dilatation occurred in an incarcerated hiatus hernia, resulting in left ventricular failure in the postoperative period. Failure to recognize this gave rise to concern when the patient re-presented for further surgery. PMID- 2917105 TI - Hypotensive agents: an animal model. PMID- 2917106 TI - Spinal anaesthesia with bupivacaine. PMID- 2917108 TI - Spinal anaesthesia and surgical blood loss. PMID- 2917107 TI - Teaching fibreoptic intubation. PMID- 2917109 TI - Awake fibreoptic intubation in the patient at high risk of aspiration. AB - This report describes our experiences with 129 awake oral and nasal fibreoptic intubations in 123 patients considered to be at high risk of aspiration of gastric contents. I.v. sedation was used on all but six occasions. Local anaesthesia was applied to the larynx and trachea through the working channel of the fibrescope on 85 occasions, and by transtracheal injection on 29. Rigid laryngoscopy was necessary after fibreoptic laryngoscopy failed in one patient (with a bleeding peptic ulcer) who vomited a large amount of fresh and clotted blood. No other patient regurgitated during the procedure, and no patient developed evidence of aspiration. PMID- 2917110 TI - Studies on morphine disposition: influence of general anaesthesia on plasma concentrations of morphine and its metabolites. AB - The kinetics of morphine were studied during balanced anaesthesia in 10 patients undergoing lower abdominal or body surface surgery, and compared with those obtained in nine awake patients receiving morphine i.v. for the relief of chronic non-cancer pain. All patients received morphine sulfphate pentahydrate 10 mg i.v. over 30 s. Venous blood samples were collected for up to 180 min, and plasma concentrations of morphine, morphine-3-glucuronide (M3G), and morphine-6 glucuronide (M6G) assayed by a differential radioimmunoassay technique. There were no differences between groups with respect to the elimination half-life (awake group: 207 min; anaesthetized group: 153 min), volume of distribution at steady state (awake: 147 litre; anaesthetized: 128 litre), or clearance (awake: 587 ml min-1; anaesthetized: 766 ml min-1). Peak concentrations of M3G were similar in the two groups, but the peak concentration of M6G was greater in the anaesthetized patients. The AUC for M3G and M6G (0-180 min) also were greater in the anaesthetized patients, presumably as a result of decreases in renal blood flow and glomerular filtration rate during halothane anaesthesia. PMID- 2917111 TI - Defining a standard intubating position using "angle finder". AB - Study of patients who exhibit only limited morphological abnormality yet present difficulty with direct laryngoscopy is facilitated by a standard intubating position. The "Angle Finder" instrument allows implementation of a simple reproducible geometric standard which is applied easily in formal research work and in clinical practice and teaching. The proposed standard relates to the curved (Macintosh) laryngoscope blade and a supine patient. The lower neck flexion is 35 degrees and extension of the plane of the face 15 degrees, each angle measured relative to horizontal. Initially, the standard was derived from a review of the literature, then validated in a study of the intubating practices of 10 senior anaesthetists. A more detailed study of 10 normal volunteers confirmed reproducibility and, for nine patients with a history of difficult direct laryngoscopy, the standard was shown to be appropriate. PMID- 2917112 TI - Early cortical auditory evoked response in anaesthesia: comparison of the effects of nitrous oxide and isoflurane. AB - Previous studies showing graded changes in the early cortical waves Pa and Nb of the auditory evoked response (AER) with increasing concentration of volatile anaesthetic agents demonstrated high amplitudes of these waves in the period immediately following induction of anaesthesia and tracheal intubation, when the patient breathed nitrous oxide alone. These high amplitude waves were not consistent with extrapolation of the data or observations of patients under steady-state nitrous oxide anaesthesia. In order to discriminate between effects in the period immediately following induction of anaesthesia and tracheal intubation, and effects caused by nitrous oxide alone, a randomized cross-over study was performed. Eight patients breathed either nitrous oxide or isoflurane at 0.6 MAC for three consecutive 10-min periods following intubation and before surgery. The amplitudes of Pa and Nb were significantly less for isoflurane with respect to the same MAC fraction of nitrous oxide in all periods, but for both agents the amplitudes were significantly greater in the 10 min following intubation than in subsequent periods, presumably as a result of stimulation. PMID- 2917113 TI - Adrenal cortical reserve in patients undergoing muscle biopsy for malignant hyperthermia screening. AB - Stress has been suggested as a factor involved in the development of a malignant hyperthermia (MH) reaction. This study has compared the hormonal response of a group of patients susceptible to MH (MHS), with that of a control group, during diagnostic muscle biopsy under general anaesthesia. Preoperative adrenal cortical reserve was assessed using the Short Synacthen Test (SST). There was no significant difference between the groups in their hormonal response to the procedure, both groups showing a peroperative reduction in plasma cortisol concentration from an initially high value, and the SST was within accepted normal limits for both groups. It was concluded that patients susceptible to MH have normal adrenal cortical reserve and responded normally to the psychological and surgical stress encountered during this study. PMID- 2917114 TI - Glycopyrronium requirements for antagonism of the muscarinic side effects of edrophonium. AB - We have compared, in 60 adult patients, the cardiovascular effects of glycopyrronium 5 micrograms kg-1 and 10 micrograms kg-1 given either simultaneously or 1 min before edrophonium 1 mg kg-1. Significant differences between the four groups were detected (P less than 0.001). Both groups receiving 10 micrograms kg-1 showed increases in heart rate of up to 30 beat min-1 (95% confidence limits 28-32 beat min-1). Use of glycopyrronium 5 micrograms kg-1 provided greater cardiovascular stability and, given 1 min before the edrophonium, was sufficient to minimize early, edrophonium-induced bradycardias. This low dose of glycopyrronium provided good control of oropharyngeal secretions. PMID- 2917115 TI - Extradural bupivacaine and methadone for extracorporeal shock-wave lithotripsy. AB - Combined extradural bupivacaine and methadone analgesia was investigated in 144 patients who underwent extracorporeal shock wave lithotripsy (ESWL). Patients were assigned randomly to one of three groups: group I--extradural 0.5% bupivacaine hydrochloride 0.75 mg kg-1; group II--extradural 0.1% methadone hydrochloride 4 mg after the bupivacaine; group III--as group II, plus a continuous extradural infusion of methadone 0.3 mg h-1 after operation. In all patients, only partial motor deficit occurred. During ESWL, patients who received extradural bupivacaine and methadone had significantly less pain compared with those who had bupivacaine alone (P less than 0.025). Extradural anaesthesia and immersion in the warm water bath were accompanied by only mild fluctuations in arterial pressure. After ESWL, significantly more patients with continuous methadone infusion were pain free (P less than 0.05) and they required less systemic analgesics. The anaesthesia during and after the ESWL procedure may be carried out safely and effectively by the administration of small doses of bupivacaine combined with methadone followed by infusion of the opioid. PMID- 2917116 TI - Does pretreatment with cimetidine and ranitidine affect the disposition of bupivacaine? AB - Thirty patients who chose extradural analgesia for elective Caesarean section were pretreated, by random selection, with cimetidine 400 mg, ranitidine 150 mg or no H2-blocker. Following the administration of 0.5% bupivacaine, no significant difference was found between peak plasma bupivacaine concentrations or area under the plasma bupivacaine concentration-time curve (AUC) in these three groups. This study shows that a single dose of cimetidine or ranitidine does not affect significantly the disposition of bupivacaine in the obstetric patient. PMID- 2917117 TI - Use of continuous prolonged administration of atracurium in the ITU to a patient with myasthenia gravis. AB - The case is described of a patient with myasthenia gravis who required prolonged controlled ventilation for respiratory failure. Muscular relaxation was obtained with a continuous infusion of atracurium 5 mg h-1 for 45 h. Following cessation of the infusion, paralysis disappeared rapidly. PMID- 2917118 TI - Severe Hb S-beta zero-thalassaemia with a T----C substitution in the donor splice site of the first intron of the beta-globin gene. AB - Through direct sequencing and dot-blot analyses with synthetic oligonucleotide probes of amplified DNA, a new nucleotide substitution was discovered in a Black teenager with severe Hb S-beta zero-thalassaemia. The substitution involved a T-- -C replacement at the second position of the donor splice site of the first intervening sequence of the beta-globin gene. The clinical and haematological observations made in Black subjects with Hb S-beta zero-thalassaemia, with different types of thalassaemia, suggest severe disease resembling sickle cell anaemia. Only an occasional patient had a milder clinical course, perhaps because of a greatly increased production of fetal haemoglobin. PMID- 2917119 TI - Maternal alloimmunization to HLA, platelet and granulocyte-specific antigens during pregnancy: its influence on cord blood granulocyte and platelet counts. AB - In order to obtain an estimate of the frequency of platelet-specific and granulocyte-specific antibodies and of the effect of such antibodies on the platelet count and granulocyte count of the newborn infant, serum from 147 women in their second or subsequent pregnancies was tested. No platelet-specific antibodies were found but 29 of the women had granulocyte-specific antibodies and the corresponding infants had granulocyte counts which were significantly lower than those of infants without antibodies. HLA antibodies were found in the sera of 57 women but were not associated with diminished platelet or granulocyte counts in the corresponding infants. Maternal granulocyte antibodies may be an underestimated contributory factor in the pathogenesis of neonatal neutropenia. PMID- 2917120 TI - Characterization of deletions of chromosome 7 short arm occurring as primary karyotypic anomaly in acute myeloid leukaemia. AB - Three patients with an acute myeloid leukaemia (AML) showed a deletion of the short arm of chromosome 7 with loss of the deleted material. The 7p- anomaly originated from either a terminal or an interstitial deletion and it represented the only karyotypic aberration in all the three cases. According to the clinical, morphological and immunological features of this series of patients, a 7p- chromosome appears to be associated with a group of AML with myelodysplastic features in the bone marrow, including secondary disorders in patients treated for a previous malignancy. PMID- 2917121 TI - Spectrin autoantibodies in normal human serum and in polyclonal blood grouping sera. AB - Naturally occurring spectrin autoantibody was detected in normal human sera and in polyclonal blood grouping sera by the immunoblotting technique. The autoantibody seems to be IgG, stable, of high titre and low affinity. It was detected in all sera tested. Preparations of monoclonal antibodies directed against some blood group antigens and anti-A1 lectin reagent were devoid of spectrin autoantibody as expected. This autoantibody may be instrumental in clearing red cell membrane components from the circulation during haemolysis. Care must be exercised in studies designed to determine the association of some blood group antigens with the red cell membrane skeleton, when using polyclonal sera which contain spectrin autoantibodies in addition to the antibodies against the blood group antigen in question. PMID- 2917122 TI - Reduction of membrane band 7 and activation of volume stimulated (K+, Cl-) cotransport in a case of congenital stomatocytosis. AB - We report on a case of congenital stomatocytosis in a French boy presenting with a haemolytic anaemia requiring splenectomy at the age of 6. The red cells included 15-20% stomatocytes and displayed a marked increase of volume. Their osmotic resistance and density were reduced; however, their deformability was unaltered in isotonicity. Erythrocyte Na+ was high (27 mEq/l) and K+ low (65 mEq/l). The newly described (K+, Cl-)-cotransporter normally triggered by hypo osmotic stress, was activated to maximal capacity. Membrane band 7 was reduced by 72%. From anamnestic data, the condition appears to have been transmitted by the father. The mother proved to be strictly normal on clinical, morphological, osmotic and biochemical bases. We suggest that the partly missing band 7 may play an important role in the genesis of stomatocytosis. PMID- 2917123 TI - Haematological changes during acute mental stress. AB - To study haematological effects of emotional stress, blood samples were obtained from 29 healthy, normotensive, non-smoking males aged 20-34 years before, during and after 10 min of mental arithmetic. There were significant increases in peripheral blood cell count, haemoglobin concentration, and haematocrit in response to mental stress. Parallel to these changes significant increases in heart rate, and systolic and diastolic blood pressure were observed. The relative increments of leucocyte (8%) and platelet (3.5%) count were significantly higher than the increase in haemoglobin concentration (2%). There was a significant positive correlation between the blood pressure increase and the mobilization of leucocytes, whereas the increase in erythrocyte count, haemoglobin concentration, and haematocrit showed significant positive correlations with heart rate reactivity. It is concluded that mental stress causes an increase in leucocyte and platelet count that could not solely be accounted for by the concurrent haemoconcentration. PMID- 2917124 TI - Bone marrow morphology at diagnosis as a prognostic parameter in Philadelphia positive chronic myelogenous leukaemia (CML) PMID- 2917125 TI - Scientific meeting of the British Society for Haematology. London, 1 December 1988. Abstracts. PMID- 2917126 TI - Chemosensitivity testing of fresh leukaemia cells using the MTT colorimetric assay. AB - We have determined the feasibility of using the MTT colorimetric assay for measuring the sensitivity of fresh leukaemia cells to cytotoxic agents. A linear relationship was seen between the number of leukaemic cells plated and the resulting absorbance in the MTT assay at day 4. For 2 X 10(5) cells/well from CLL peripheral lymphocytes, the mean absorbance (measured at 540 nm) was 0.41. Similar curves were obtained with the assay carried out between days 3 and 7. ID50 values for CLL lymphocytes exposed to adriamycin (ADM) were in the range of 0.02-0.29 micrograms/ml, a similar range to that given by the DiSC dye exclusion assay. Sensitization of leukaemia cells to ADM by verapamil or cyclosporin A could be demonstrated in some patients but not in others. The lymphocytes from one patient with prolymphocytic leukaemia were abnormally resistant to ionizing radiation. These cells also showed resistance to melphalan and adriamycin but not to vincristine. The MTT assay appears to offer an attractive option for in vitro chemosensitivity testing in leukaemia, determination of cross-resistance profiles and studies of resistance modifiers. PMID- 2917127 TI - A translocation involving a specific breakpoint (q35) on chromosome 5 is characteristic of anaplastic large cell lymphoma ('Ki-1 lymphoma'). AB - Two cases of non-Hodgkin's lymphoma are reported in which a chromosomal translocation was observed involving the same site (q35) on the long arm of chromosome 5. The other breakpoint involved in the translocation was chromosome 2 (p23) in one case and chromosome 3 (q12) in the other. Both cases were large cell lymphomas expressing CD30 antigen ('Ki-1 lymphoma'). One was clearly of T lymphoid origin, the other probably B cell derived. One other case of a Ki-1 lymphoma with 2;5 translocation (involving the same breakpoint on chromosome 5) has been reported previously, and it is suggested that this cytogenetic abnormality may be specifically associated with Ki-1 lymphoma. The literature contains a further eight cases of lymphoid neoplasms with a translocation involving a breakpoint at q35 on chromosome 5. They have all been described as cases of 'malignant histiocytosis', but the present findings make it likely that these cases were in reality also examples of Ki-1 lymphoma. The breakpoint at the q35 region on chromosome 5 is close to the position of the fms proto-oncogene, suggesting that an abnormality affecting this gene might possibly play a causal role in 'Ki-1 lymphoma'. However, DNA restriction fragment analysis of the present cases showed no evidence that the breakpoint on chromosome 5 involves the fms gene or its immediate vicinity. PMID- 2917128 TI - Children in long-term remission after treatment for acute lymphoblastic leukaemia show persisting haemopoietic injury in clonal and long-term cultures. AB - Twenty children who were in unmaintained full haematological remission after treatment for acute lymphoblastic leukaemia (ALL) showed a significantly lower incidence of granulocyte-macrophage progenitor cells (GM-CFC) in the bone marrow compared to controls. This low incidence lasted for up to at least 3 years after the cessation of chemotherapy. There was no tendency to higher values with longer times after treatment, and the low incidence was not predictive of relapse. Long term cultures from ALL bone marrows and from controls achieved similar levels of production of mature cells through the whole period of culture (6 weeks). However, cultures from patients' bone marrow had on average about 5 times lower numbers of GM-CFC, indicating that the level of mature cell production was achieved by a higher level of post-GM-CFC amplification than needed in the controls. This is taken to be due to compensatory mechanisms operative during stressed haemopoiesis which appears to be a long-lasting effect after current chemotherapy of ALL. PMID- 2917129 TI - PL2-49, a monoclonal antibody against glycoprotein IIb which is a platelet activator. AB - PL2-49 is a murine monoclonal IgG1 antibody obtained after immunization of Balb/c mice with EDTA washed platelets. Binding could be detected on Zwa(+) as well as Zwa(-) platelets, but not on type I Glanzmann's thrombasthenia platelets using an ELISA screening test. Immunoprecipitation studies showed that PL2-49 bound to glycoprotein IIb when the glycoprotein IIb/IIIa complex dissociation was performed after the monoclonal antibody binding. Experiments with a human alloantibody against Zwa antigen were run in parallel to control the complex dissociation. Ascitic fluid, as well as the purified antibody, induced activation and aggregation of washed platelets and ATP release. PL2-49-induced aggregation did not require exogenous fibrinogen and was inhibited, partially, in the presence of aspirin, apyrase, isosorbide dinitrate. Raising intra-platelet cyclic AMP with a stable PGI2 analogue, iloprost, and/or a phosphodiesterase inhibitor, RA 233, suppressed the responses to PL2-49. F(ab')2 fragments did not induce aggregation of normal platelets but inhibited the response to the whole immunoglobulin. Finally PL2-49 was shown to induce aequorin-detected elevations in intraplatelet Ca++ levels. Thus PL2-49 seems to differ from monoclonal antibodies so far described, since it binds to glycoprotein IIb in a complex dependent manner at least under our experimental conditions for immunoprecipitation studies, and it induces platelet Ca++ mobilization and platelet aggregation after a lag-time. These reactions depend both on Fab and Fc domains of the antibody and require neither complement nor exogenous fibrinogen. PMID- 2917130 TI - Plasma D-dimer levels and their relationship to serum fibrinogen/fibrin degradation products in hypercoagulable states. AB - Plasma D-dimer was measured and compared with serum fibrinogen/fibrin degradation product levels (FDPs) in patients with disseminated intravascular coagulation (DIC) and other conditions associated with a hypercoagulable state. D-dimer (N less than 200 ng/ml) was elevated in all 43 patients with DIC, in 48 of 59 patients with liver disease, in 22 of 27 patients with acute leukaemia at presentation, in 17 of 23 patients with malignant disease, in 29 of 39 women in the third trimester of a complicated pregnancy, in 17 of 18 patients with deep venous thrombosis and in only four of 27 patients with acute myocardial infarction. There was a significant correlation between plasma D-dimer and serum FDP levels (P less than 0.01) as follows; DIC: r = 0.58, liver disease: r = 0.57, acute leukaemia: r = 0.84, malignancy: r = 0.87. The frequent elevation of D dimer observed in liver disease, acute leukaemia, malignancy and complicated pregnancy indicates that a hypercoagulable state is a common occurrence in these conditions although in liver disease elevated levels resulting from a failure of normal clearance mechanisms cannot be excluded. The close relationship between D dimer and FDP levels suggests that serum FDPs predominantly arise from the interaction of plasmin with crosslinked fibrin rather than with fibrinogen in the conditions in which these were compared. PMID- 2917131 TI - Amodiaquine-induced immune agranulocytosis. AB - This report describes two patients who developed agranulocytosis while receiving prophylactic amodiaquine treatment. The neutrophil counts returned to normal in one after stopping the drug while the other died of sepsis. Amodiaquine-dependent circulating neutrophil IgG antibodies were demonstrated in both patients using the indirect granulocyte immunofluorescence test. The antineutrophil antibody activity was enhanced with the use of the major amodiaquine metabolite, mono desethyl amodiaquine. Additional studies showed the activity of the sera to be nondialysable, heat stable, active against autologous as well as allogenic cells, and absent from the convalescent sera. There was no growth inhibition of allogenic myeloid committed progenitor cells (CFU-GM) following incubation with the patients' sera, complement and amodiaquine. These results indicate that agranulocytosis can be mediated by a drug-dependent antibody which affects mature blood cells. PMID- 2917132 TI - Mortality and causes of death in Dutch haemophiliacs, 1973-86. AB - Mortality figures were calculated for a group of 717 Dutch haemophiliacs over the period 1973-86. Follow-up was on average 10.9 years; no patients were lost to follow-up. The data were compared to the general male population by actuarial methods and patient-year analysis. Forty-three patients died, while 20 deaths were expected in a hypothetical group of non-haemophiliacs of the same age distribution. Hence, overall mortality was 2.1 times higher than in the general population. This leads to a calculated life expectancy of 66 years, as compared to 74 years in the general male population. Mortality did not differ much by severity of haemophilia. A possibly beneficial effect of prophylaxis on longevity was observed. Haemorrhage occurred in half of all deaths and among these traumatic bleeding was the most prevalent. The number of deaths due to ischaemic heart disease was significantly lower (80% reduction) than expected and therefore the authors conclude that haemophilia offers protection against ischaemic heart disease. Cancer mortality was significantly higher (2.5 times) than expected. PMID- 2917133 TI - Antithrombin Sheffield: amino acid substitution at the reactive site (Arg393 to His) causing thrombosis. AB - A Sheffield family with a predisposition towards thrombosis has been shown to have a functional abnormality of antithrombin. The abnormality was detected as reduced heparin cofactor activity, with normal antigenic levels of antithrombin. Crossed immunoelectrophoresis performed in the absence and presence of heparin was normal. The antithrombin was isolated by heparin Sepharose affinity chromatography. It had normal mobility on SDS polyacrylamide gel electrophoresis. However, the second order rate constant of inhibition of thrombin was about half that of normal, and this was compatible with a heterozygous abnormality involving the reactive site. The antithrombin was further purified by chromatography on thrombin-Sepharose (to remove the normal component), reduced, S-carboxymethylated and fragmented with cyanogen bromide. A pool containing the reactive site region was digested with trypsin and the molecular size of peptides generated determined by fast atom bombardment mass spectrometry. The two peptides adjacent to the Arg393-Ser394 bond of mass 2290 and 700 were almost absent from the mass spectrum, but an additional peptide of mass 2952 was present. Subdigestion with V8 protease reduced the mass of this peptide to 1748. These peptides generated by trypsin and V8 protease were almost identical to those obtained when another variant, antithrombin Glasgow, was treated in the same way (Erdjument et al, 1988). It is concluded that the molecular abnormality of antithrombin Sheffield is identical to that of antithrombin Glasgow, Arg393 to His. PMID- 2917134 TI - A prospective comparison of four techniques for measuring platelet-associated IgG. AB - We describe a prospective study comparing four different assays for PAIgG. Platelets from patients with a variety of thrombocytopenic disorders were collected into ACD, washed, and the PAIgG then measured using three assays for surface PAIgG. These included: (a) a direct binding assay using 125I-monoclonal anti-IgG (MoAb); (b) a direct binding assay using 125I-staphylococcal protein A (SPA); and (c) a two-stage assay. PAIgG also was measured using an assay for 'total' PAIgG following platelet lysis. The mean +/- SD number of molecules of IgG per platelet on washed platelets from 29 healthy, non-thrombocytopenic controls was: 86 +/- 80 (125I-MoAb); 94 +/- 96 (125I-SPA); 3520 +/- 1890 (two stage surface assay); and 10,850 +/- 3720 (total PAIgG). A total of 62 different patients with idiopathic thrombocytopenic purpura or thrombocytopenia complicating systematic lupus erythematosus, and 73 different patients with 'non immune' thrombocytopenia, were tested using each of the four assays. These 'non immune' thrombocytopenic patients included patients with carcinoma, septicaemia, pre-eclampsia, chronic leukaemia, thrombotic thrombocytopenic purpura, haemolytic uraemic syndrome, acute leukaemia and myelodysplasia. All four assays gave similar results for both the immune and non-immune thrombocytopenic patients. The sensitivity of the assays for the most severely thrombocytopenic patients with immune thrombocytopenia was: MoAb 60%; SPA 88%; two-stage 82%; and 'total' PAIgG 88%. The specificity of the four assays in the non-immune thrombocytopenic patients was 57% 'total' PAIgG; 63% two-stage surface; 25% SPA; 38% MoAb.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2917135 TI - Interaction of bile salt monomer and cholesterol in the aqueous phase. AB - The purpose of the present study was to evaluate the possible interaction of bile salt monomer and cholesterol in the intermicellar aqueous phase. Cholesterol and taurocholate monomer concentrations in the intermicellar aqueous phase were determined using 0-20 mM taurocholate solutions saturated with cholesterol. Maximal solubilities of cholesterol in aqueous solutions having various concentrations of taurocholate, especially below its intermicellar monomer concentration (critical micellar concentration), were determined and compared with the intermicellar cholesterol concentration. The intermicellar monomer concentration of taurocholate was constant (6 mM) and independent of taurocholate concentrations. The cholesterol concentration in the intermicellar aqueous phase gradually increased, depending upon taurocholate concentrations, and became constant (1,3 microM) above 10 mM taurocholate. The solubility of cholesterol increased linearly with the taurocholate concentration even below the critical micellar concentration, and was 0.3 microM at 6 mM taurocholate, which was approx. 20-times higher than the aqueous solubility of cholesterol, but a fifth of the maximal intermicellar cholesterol concentration. The results indicate that the higher cholesterol concentration in the intermicellar aqueous phase compared to its aqueous solubility can be primarily ascribed to the interaction of cholesterol with bile salt monomers possibly forming bile salt-cholesterol dimers, and partly to the sustaining forces induced by numerous micelles. PMID- 2917136 TI - Control of lipoprotein lipase secretion in mouse macrophages. AB - The regulation of secretion of lipoprotein lipase (LPL) was studied in in vitro derived mouse bone marrow macrophages (BMM), peritoneal exudate and resident macrophages and in the macrophage-like tumor cell line J774.1. BMM in cultures initiated with low concentrations of bone marrow cells (LC-BMC cultures) secrete more LPL per cell than BMM in cultures initiated with high concentrations of bone marrow cells (HC-BMC cultures). The suppressed state of LPL secretion in HC-BMC cultures could be alleviated by the addition of a colony-stimulating factor source (L-cell-conditioned medium; L-CM) onto the culture medium or exchanging the medium of HC-BMC cultures with medium from LC-BMC cultures for short periods (4 h). Addition of L-CM increased LPL secretion also in LC-BMC cultures. Addition of L-CM to fresh culture medium had little or no effect, suggesting that, in addition to requirement for L-CM, optimal expression depended also on factors released by the growing cells, probably providing optimal growth conditions. L-CM enhanced LPL secretion by thioglycollate-elicited peritoneal macrophages and had no effect on LPL secretion by resident peritoneal macrophages. Secretion of LPL from adherent J774.1 cells showed a biphasic effect. Secretion increased with cell density up to the point when growth inhibition was observed. In dense cultures in which cell proliferation was almost arrested, LPL secretion was remarkably suppressed (80-90%). Change of medium of dense cultures to fresh medium or medium conditioned by sparse cultures (for the last 4 h of culture) led to enhancement of LPL secretion to levels similar to those optimally expressed by sparse cultures. L-CM did not enhance LPL secretion from J774.1 cells. Dense cultures of both BMM and J774.1 cells did not contain a stable inhibitor of LPL secretion and medium from sparse cultures did not contain an inducer of LPL secretion. The data suggest that proliferating macrophages secrete large amounts of LPL, whereas in nonproliferating, quiescent cells, this activity is much reduced. L-CM enhances LPL secretion in quiescent BMM and peritoneal exudate cells to levels expressed by proliferating cells. Since this effect is already expressed after a 4 h incubation period, it is not dependent on cell cycling but could be one of the early responses to this macrophage mitogen. In J774.1 cells, a change of medium is a sufficient signal for enhancement of LPL secretion in quiescent cells. PMID- 2917137 TI - Inhibitors of sterol synthesis. 15-oxygenated steryl ester hydrolase activity of rat liver at neutral and acid pH. AB - 5 alpha-Cholest-8(14)-en-3 beta-ol-15-one (15 ketosterol) is a potent inhibitor of cholesterol biosynthesis with significant hypocholesterolemic activity. The results of a recent study (Schroepfer, G.J., Jr., Christophe, A., Chu, A.J., Izumi, A., Kisic, A. and Sherrill, B.C. (1988) Chem. Phys. Lipids 48, 29-58) have indicated that, after intragastric administration of the 15-ketosterol in triolein to rats, most of the compound in intestinal lymph occurs in the form of the oleate ester, which is associated with chylomicrons. Moreover, after intravenous administration of chylomicrons containing the oleate ester of 15-[2,4 3H]ketosterol, rapid and selective uptake of 3H by liver was observed, which was associated with the rapid and substantial appearance of labeled free 15 ketosterol in liver. The present study concerns the capabilities of rat liver fractions to catalyze the hydrolysis of 15-ketosteryl oleate. Efficient hydrolysis was observed at acid pH with a digitonin-solubilized extract of rat liver, with a rate similar to that for the hydrolysis of cholesteryl oleate. The distribution of acid 15-ketosteryl oleate hydrolase of whole liver homogenate on a metrizamide isopycnic density gradient was similar to that of acid cholesteryl oleate hydrolase and acid phosphatase, suggesting that the lysosomal acid lipase is the enzyme responsible for the hydrolysis of the 15-ketosteryl oleate at acid pH. At neutral pH, 15-ketosteryl oleate and cholesteryl oleate was hydrolyzed at similar rates by the microsomal fraction of liver homogenate, whereas the 15 ketosteryl oleate was hydrolyzed at a much lower rate than cholesteryl oleate by the cytosolic fraction. The distribution of neutral 15-ketosteryl oleate hydrolase activity of whole liver homogenate on a metrizamide isopycnic density gradient was most correlated to a microsomal esterase, whereas cholesteryl oleate hydrolase activity was most correlated to a cytosolic enzyme. Both 15-ketosteryl oleate and cholesteryl oleate hydrolase activities were correlated to a mitochondrial marker enzyme. PMID- 2917138 TI - Variations of hepatic cholesterol precursors during altered flows of endogenous and exogenous squalene in the rat. AB - Hepatic and serum levels of cholesterol precursors were analyzed in rats under basal (control) conditions and when cholesterol synthesis was activated by feeding 1% squalene or 5% cholestyramine. Exogenous squalene stimulated the activity of acyl-coenzyme A:cholesterol acyltransferase (ACAT) but strongly inhibited the activity of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase; cholestyramine did not affect ACAT but increased HMG-CoA reductase several-fold, indicating enhanced production of endogenous squalene. Activation of cholesterol synthesis by the two methods markedly increased the hepatic and serum contents of cholesterol precursor sterols. However, the sterol profiles were clearly different. Thus, exogenous squalene raised most significantly (up to 109-fold) free and esterified methyl sterols, and less so (up to 2-fold) demethylated C27 sterols (desmosterol and cholestenols) and also esterified cholesterol. Activation of endogenous squalene production by cholestyramine was associated with a depletion of esterified cholesterol and by a marked, up to 8-fold, increase of the free demethylated sterol precursor levels, whereas the increase of methyl sterols, up to 5-fold, was less conspicuous than during the squalene feeding. The changes were mostly insignificant for esterified sterols. The altered serum sterol profiles were quite similar to those in liver. Serum cholestenols and especially their portion of total serum precursor sterols were closely correlated with the hepatic activity of HMG-CoA reductase. PMID- 2917139 TI - Structural and compositional difference in the neutral glycolipids between epithelial and non-epithelial tissue of the mouse small intestine. AB - Five major neutral glycolipids, GL-1-GL-5, were isolated from the mouse small intestine. Their structures and distribution were determined by permethylation analysis, sequential degradation with exoglycosidases and/or immunohistochemistry. The molar ratio of GL-1, GL-2, GL-3, GL-4 and Gl-5 in the whole small intestine was 1:0.04:0.03:0.42:0.02. The structures of GL-1 and GL-4 present in epithelial cells were reported previously to be glucosyl ceramide and asialo GM1, respectively (Umesaki, Y., Suzuki, A., Kasama, T., Tohyama, K., Mutai, M. and Yamakawa, T. (1981) J. Biochem. 90, 1731-1738). GL-5, also present in the epithelial cells, was fucosyl asialo GM1, and fucose was shown to be linked to terminal galactose of asialo GM1 in the manner of alpha(1-2) bond. GL-2 and GL-3, present in the residual tissue after scraping the mucosa, were determined to be globoside and Forssman glycolipid, respectively. Both globoside and Forssman glycolipid of the non-epithelial tissue had non-hydroxy fatty acid (C16-C24) in combination with sphingosine (C18) as the ceramide components, in contrast with the ceramide structures of the epithelial glycolipids, which contained alpha-hydroxy fatty acids in combination with phytosphingosine. Immunohistochemical staining using anti-glycolipid antibodies confirmed the distribution of asialo GM1 and fucosyl asialo GM1, and Forssman glycolipid in the epithelial and non-epithelial tissue, respectively. PMID- 2917140 TI - Factors regulating the expression of the neutral glycolipids in the mouse small intestinal mucosa. AB - GDP-fucose:asialo GM1 alpha(1-2)fucosyltransferase (FT) is induced in the small intestinal mucosa after microbial contamination of germ-free mice (Umesaki, Y., Sakata, T. and Yajima, T. (1982) Biochem. Biophys. Res. Commun. 105, 439-443). As a result, asialo GM1 glycolipid, a major component of the epithelial cell membrane, drastically converted into fucosyl asialo GM1. There were many other examples in which FT was induced. One was the weaning period for conventional mice. Others included injuries of the small intestine by punctures or administration of cytosine arabinoside, and the injection of protein synthesis inhibitors, such as cycloheximide or emetine, or the soluble fraction of the small intestinal homogenate (SISF). The induction of FT was more rapid after injection of cycloheximide or SISF than after injury, mechanical puncturing or after administration of cytosine arabinoside. The changes in the neutral glycolipids of the small intestine by injection of cycloheximide or SISF were analyzed in detail. FT activity started to increase after approx. 5 h and reached the maximum 10-12 h after injection of cycloheximide or SISF, and rapidly declined thereafter. The conversion of asialo GM1 into fucosyl asialo GM1 started after about 10 h and reached the maximal value 24 h after the treatment. Fucosyl asialo GM1 persisted for a few days, although the FT activity fell to near the basal level. On the other hand, the amount of glucosyl ceramide was constant after these treatments. There was little difference in the time-courses of both the FT activity and the glycolipid conversion between these treatments. In the case of co-injection of cycloheximide and SISF, the effect of both materials on FT activity induction was synergistic. The distribution of FT activity and immunohistochemical staining using anti-fucosyl asialo GM1 antibody along the crypt-villus axis showed a stronger expression of fucosyl asialo GM1 in villus portion, the post-mitotic cell zone, than in the crypt portion. Asialo GM1 was converted into fucosyl asialo GM1 after the induction of FT by the various treatments mentioned above. Especially the effects of cycloheximide and/or SISF on FT induction suggest at least the presence of a regulatory protein(s) which controls the glycolipid expression in the small intestine. PMID- 2917141 TI - Bile acid synthesis and secretion by rabbit hepatocytes in primary monolayer culture: comparison with rat hepatocytes. AB - Rabbit hepatocytes isolated after liver perfusion with collagenase were maintained in primary monolayer culture for periods up to 96 h. Bile acid synthesis and secretion was measured by capillary gas-liquid chromatography and by a rapid enzymatic-bioluminescence assay. As expected from the bile acid profile of rabbit gallbladder bile, cholic acid was the only bile acid synthesized in detectable amounts and was produced at a linear rate of 170 pmol/h per mg cell protein from 24 to 96 h in culture. Ketoconazole (20 microM) inhibited cholic acid synthesis and secretion by 78%, whereas the bile acids chenodeoxycholic acid (100 microM), deoxycholic acid (100 microM) or lithocholic acid (2 microM) had no effect. When rat hepatocytes were cultured under identical conditions, the rate of bile acid synthesis was found to be only 12 pmol/h per mg cell protein, a value in agreement with previous work. The large difference in rates of bile acid synthesis between rabbit and rat hepatocytes may be due to rapid loss of cytochrome P-450 from rat hepatocytes when placed in monolayer culture. Although reportedly active in cholesterol 7 alpha-hydroxylation, form 4 cytochrome P-450 levels in rabbit hepatocytes did not correlate with rates of bile acid synthesis. PMID- 2917142 TI - Molecular species of cerebrosides in fruiting bodies of Lentinus edodes and their biological activity. AB - Cerebroside fraction was obtained from fresh fruiting bodies of Lentinus edodes and separated into ten molecular species by reverse-phase high-performance liquid chromatography. The species were identified by GLC, GC-MS and NMR. Their component glycosides and sphingoids were uniformly glucose and (4E,8E)-9-methyl 4,8-sphingadienine, respectively. The component fatty acids were 2-hydroxy acids with the carbon chain length of 16, 15, 14, 18, 24, 17, 25, 26, 22 and 23 (from major to minor). The cerebrosides with the C14-18 fatty acids showed strong fruiting-inducing activity in Schizophyllum commune. Those with the C22 and C23 ones had one-eighth and one-sixteenth of the activity, respectively, and those with C24-26 had no detectable activity. 22 and 23 must be the carbon chain lengths of the component fatty acid of the sphingolipids critical for expression of biological activity. PMID- 2917143 TI - Role of the 8-double bond of lanosterol in the enzyme-substrate interaction of cytochrome P-450(14DM) (lanosterol 14 alpha-demethylase). AB - The role of the 8-double bond of lanosterol in the enzyme-substrate interaction of yeast cytochrome P-450(14DM) (lanosterol 14 alpha-demethylase) was studied by analyzing metabolism of 8-lanostene-3 beta,32-diol, 7-lanostene-3 beta,32-diol, 6 lanostene-3 beta,32-diol and lanostane-3 beta,32-diol by the cytochrome. 8 Lanostene-3 beta,32-diol was actively metabolized by cytochrome P-450(14DM) and converted to the 32-nor-14-unsaturated metabolite. 7-Lanostene-3 beta,32-diol was also metabolized by the cytochrome, but the rate of metabolism was low. However, the cytochrome failed to catalyze the conversion of 6-lanostene-3 beta,32-diol and lanostane-3 beta,32-diol to their 32-nor metabolites. Spectral analysis of the sterol-cytochrome complexes and kinetics of cytochrome P-450(14DM) reduction in the presence of the sterols indicated that 6-lanostene-3 beta,32-diol and lanostane-3 beta,32-diol could not interact with the substrate site of the cytochrome. These results revealed that the 8-double bond of lanosterol plays an important role in the enzyme-substrate interaction of cytochrome P-450(14DM). PMID- 2917145 TI - Bile acid synthesis and intracellular and extracellular cholesterol concentrations in isolated rat hepatocytes: the effect of dietary cholesterol. AB - Bile acid synthesis in isolated hepatocytes prepared from rats given 1% cholesterol in the diet and incubated for 1 h in suspension was not increased compared to that in cells from control rats. When the hepatocytes were maintained in monolayer culture for 24 h, however, increased production of bile acid (X2.5) was observed in the cholesterol-fed group. The amount of bile acid synthesised during incubation in suspension was significantly correlated with intracellular unesterified cholesterol levels, but showed no correlation with intracellular esterified or medium cholesterol concentrations after 1 h. Bile acid production in hepatocytes maintained in monolayer culture was also significantly correlated with the intracellular unesterified, but not esterified, cholesterol content. In addition, in this case, there was a significant correlation with the levels of both unesterified and esterified cholesterol found in the medium after 24 h. These results suggest that the amount of cholesterol available to liver cells from extracellular sources has a role in the regulation of bile acid synthesis in cholesterol-fed rats, while the concentrations of esterified cholesterol stored within the cells are not important in this process. PMID- 2917144 TI - Immunochemical quantitation of fatty-acid-binding proteins. I. Tissue and intracellular distribution, postnatal development and influence of physiological conditions on rat heart and liver FABP. AB - Antisera against rat heart and liver fatty acid-binding protein (FABP) were applied in Western blotting analysis and ELISA to assess their tissue and intracellular distribution, and the influence of development, physiological conditions and several agents on the FABP content of tissue cytosols. The data obtained are compared with the oleic acid-binding capacity. Heart FABP is found in high concentrations in heart, skeletal muscles, diaphragm and lung, and in lower concentrations in kidney, brain and spleen, whereas liver FABP is limited to liver and intestine. In heart and liver, FABP is only present in the cytosol. The FABP content of both heart and liver shows a progressive increase during the first weeks of postnatal development, in contrast to their constant oleic acid binding capacity. The reciprocally declining alpha-fetoprotein content of both tissues may partially account for the complementary fraction of the fatty acid binding capacity. The FABP content and the fatty acid-binding capacity of adult heart and liver were in good accordance under various physiological conditions. Addition of clofibrate to the diet induces an increase of liver FABP content, whereas feeding of cholesterol, cholestyramine, mevinolin or cholate caused a marked decrease. The significance of the combined determination of fatty acid binding capacity and FABP content (by immunochemical quantitation and blotting analysis) is indicated. PMID- 2917146 TI - Treatment of CHO-K1 cells with 25-hydroxycholesterol produces a more rapid loss of 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity than can be accounted for by enzyme turnover. AB - A key enzyme in the regulation of mammalian cellular cholesterol biosynthesis is 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase). It is well established that treatment with the compound 25-hydroxycholesterol lowers HMG-CoA reductase activity in cultured Chinese hamster ovary (CHO-K1) cells. After brief incubation (0-4 h) with 25-hydroxycholesterol (0.5 microgram/ml), cellular HMG CoA reductase activity is decreased to 40% of its original level. This also occurs in the presence of exogenous mevinolin, a competitive inhibitor of HMG-CoA reductase which has previously been shown to inhibit its degradation. The inhibition of HMG-CoA reductase activity by 25-hydroxycholesterol is complete after 2 h. Radio-immune precipitation analysis of the native enzyme under these conditions shows a degradation half-life which is considerably longer than that of the observed inhibition. Studies with sodium fluoride, phosphatase 2A, bacterial alkaline phosphatase and calf alkaline phosphatase indicate that the observed loss of activity is not due to phosphorylation. These data are not consistent with described mechanisms of HMG-CoA reductase activity regulation by phosphorylation or degradation but are consistent with a novel mechanism that regulates the catalytic efficiency of this enzyme. PMID- 2917147 TI - Phosphatidylcholine and triacylglycerol hydrolysis in HDL as induced by hepatic lipase: modulation of the phospholipase activity by changes in the particle surface or in the lipid core. AB - (1) Human HDL2 (d 1.063-1.125) and HDL3 (d 1.125-1.210), labelled with 2 [14C]oleoylphosphatidylcholine (PC), and with/without tri[3H]oleoylglycerol, were incubated with a partially purified human hepatic triacylglycerol lipase, at pH 8.5. PC hydrolysis was linear up to 90-120 min incubation and within a range of lipase activities, from 50 to 500 mIU/ml. At low degrees of lipolysis, the hydrolysis of triacylglycerol was linearly related to that of PC, but the relative degradation rate was 10-fold higher for the former, which was thus very rapidly consumed. HDL subfractions were then differentiated in terms of PC hydrolysis. Km values were 0.32 and 0.43 mM for HDL2 PC and HDL3 PC, respectively. The corresponding Vmax values expressed for 200 mIU/ml hepatic lipase activity were 41.0 nmol PC hydrolysed/ml per h (HDL2) and 28.6 nmol PC/ml per h (HDL3). (2) HDL3 were modified in the presence of VLDL by inducing triacylglycerol lipolysis in VLDL with a semi-purified human plasma or bovine milk lipoprotein lipase (LPL). Lipolysis-modified HDL3 (LIP-HDL3) were mostly enriched in free cholesterol (+80%, P less than 0.05) and to a lesser extent in triacylglycerol (+33%). As a consequence, 45% of the LIP-HDL3 was reisolated in the HDL2-density interval, and is referred to as light LIP-HDL3. LIP-HDL3 displayed a 65% increase in its reactivity towards hepatic lipase compared to control HDL3. The light LIP-HDL3 showed the lowest Km (0.19 mM PC) and the highest Vmax (69 nmol/ml per h) of all HDL tested. Coincubation of HDL3 with VLDL and albumin did not alter the further reactivity of HDL3 towards hepatic lipase. Cholesterol loading of HDL3 by celite-cholesterol dispersions also led to an enhanced reactivity, though less important than with the lipolysis modification. (3) HDL3 were also modified by coincubation with VLDL and the lecithin cholesterol acyltransferase-inhibited plasma fraction of d greater than 1.21 g/ml, thus allowing the cholesteryl ester transfer reaction to occur. The modified HDL3 (CET-HDL3) were depleted in esterified cholesterol (-25%, P less than 0.05) and enriched in triacylglycerol (+70%, P less than 0.05). However, these particles behaved like control HDL3 in their reactivity towards hepatic triacylglycerol lipase. Thus, the hydrolysis of HDL PC mediated by hepatic triacylglycerol lipase appears to be influenced by changes occurring in the particle's surface rather than in the lipid core. PMID- 2917148 TI - Secretion of liver lipase activity by periportal and perivenous hepatocytes. AB - Periportal and perivenous hepatocytes were separated by isopycnic centrifugation through Percoll, or selectively isolated by combined digitonin/collagenase perfusion. With either method, secretion of liver lipase activity was 2-2.5-fold higher in periportal than perivenous cells. This acinar heterogeneity parallels that of cholesterol de novo synthesis and bile formation reported previously. PMID- 2917149 TI - The subcellular distribution of the nonspecific lipid transfer protein (sterol carrier protein 2) in rat liver and adrenal gland. AB - The distribution of the nonspecific lipid transfer protein (i.e., sterol carrier protein 2) over the various subcellular fractions from rat liver and adrenal gland was determined by enzyme immunoassay and immunoblotting. This distribution is very different in each of these two tissues. In liver, 66% of the transfer protein is present in the membrane-free cytosol as compared to 19% in the adrenal gland. In the latter tissue, the transfer protein is mainly found in the lysosomal/peroxisomal and the microsomal fraction at a level of 1093 and 582 ng per mg total protein, respectively (i.e., 17% and 35% of the total), and to a lesser extent in the mitochondrial fraction (11% of the total). Of all the membrane fractions isolated, the microsomal fraction from the liver and the mitochondrial fraction from the adrenal gland have the lowest levels of the transfer protein (i.e., 168 ng and 126 ng per mg total protein, respectively). These low levels correlate poorly with the active role proposed for this transfer protein in the conversion of cholesterol into bile acids and steroid hormones in these fractions. Using immunoblotting, it was demonstrated that in addition to the transfer protein (14 kDa) a cross-reactive 58 kD protein was present in the supernatant and the membrane fractions of both tissues. Cytochemical visualization in adrenal tissue with specific antibodies against the nonspecific lipid transfer protein showed that immunoreactive protein(s) were present mainly in the peroxisome-like structures. PMID- 2917150 TI - Effects of tetrahydrolipstatin, a lipase inhibitor, on absorption of fat from the intestine of the rat. AB - Tetrahydrolipstatin (THL) derived by hydrogenation from lipstatin, a lipase inhibitor produced by Streptomyces toxytricini, has been shown to inhibit in vitro the activity of all three lipases secreted to the gastro-intestinal tract; gastric lipase, pancreatic lipase and carboxylester lipase (cholesterol ester hydrolase). The effects of THL on intestinal absorption of fat (transport to the thoracic duct chyle) has now been investigated after intraduodenal infusion in a rat model. Absorption of label from oleic acid when administered with monoolein in micellar bile salt solution was not affected by THL in concentrations up to 10(-4) M calculated on the volume of the aqueous phase. Absorption of free cholesterol in micellar bile salt solution of the lipolytic products of triolein; oleic acid and monoolein, is not significantly affected at a concentration of THL of 10(-4) M. Absorption of cholesterol from cholesteryl oleate under the same conditions is almost completely inhibited. The results indicate that absorption of free cholesterol is not dependent on the activity of pancreatic cholesterol ester hydrolase. The absorption of emulsified triolein was not significantly affected by 10(-5) M THL but decreased to around 30% of the controls by a concentration 10-times higher. There was no significant decrease of cholesterol absorption when administered in emulsified triolein while absorption of cholesteryl oleate was reduced at both concentrations of THL and almost completely at 10(-4) M. Radioactivity from [2-14C]THL when administered emulsified in triolein was recovered in urine, bile and thoracic duct lymph to 10 14, 8-13 and 1-3%, respectively, largely independent on dose administered. Label from [1"-14C] THL was recovered in the same amounts in lymph but much less in bile and urine indicating that the amino acid moiety has been split off early in the absorption process. PMID- 2917151 TI - Co-ordinate control of CDP-choline and phosphatidylethanolamine methyltransferase pathways for phosphatidylcholine biosynthesis occurs in response to change in diet fat. AB - Brain microsomal and synaptic plasma membrane phosphatidylcholine composition and biosynthetic activity were examined in relation to the composition of diet fat fed. Phosphocholinetransferase and methyltransferase activities are shown to be modulated by the diet, and by changes in the membrane phospholipid content of long-chain polyunsaturated fatty acids. This physiological modulation is co ordinated such that the rate of phosphatidylcholine synthesis via one route is inversely regulated with activity of the alternate pathway. PMID- 2917152 TI - Identification of the molecular species of lysophosphatidic acid produced when platelets are stimulated by thrombin. AB - Platelets, when stirred with 3 U thrombin/10(9) platelets, produced significant quantities of palmitoyllysophosphatidic acid (2.17 ng/10(9) platelets), stearoyllysophosphatidic acid (2.11 ng/10(9) platelets), and arachidonoyllysophosphatidic acid (1.06 ng/10(9) platelets). When platelets were pretreated with 100 microM of the phospholipase A2 inhibitor U10029A, there was a significant decrease in thrombin-stimulated production of stearoyllysophosphatidic acid (to 0.16 ng/10(9) platelets), while arachidonoyllysophosphatidic acid production was unchanged. U10029A concomitantly increased thrombin-stimulated production of stearoyl-containing phosphatidic acid species (primarily stearoylarachidonoylphosphatidic acid) from 5.99 to 9.71 ng/10(9) platelets. The results are consistent with the concept that stearoyllysophosphatidic acid production in platelets occurs via phospholipase A2 degradation of phosphatidic acid. PMID- 2917153 TI - Fatty acids generated by gastric lipase promote human milk triacylglycerol digestion by pancreatic colipase-dependent lipase. AB - The concerted action of purified bovine gastric lipase and human pancreatic colipase-dependent lipase and colipase, or crude human pancreatic juice, in the digestion of human milk triacylglycerols was explored in vitro. Gastric lipase hydrolyzed milk triacylglycerol with an initially high rate but became severely inhibited already at low concentration of released fatty acid. In contrast, colipase-dependent lipase could not, by itself, hydrolyze milk triacylglycerol. However, a short preincubation of milk with gastric lipase, resulting in a limited lipolysis, made the milk fat triacylglycerol available for an immediate and rapid hydrolysis by pancreatic juice, and also for purified colipase dependent lipase, provided colipase and bile salts were present. The same effect was obtained when incubation with gastric lipase was replaced by addition of long chain fatty acid. Long-chain fatty acid increased the binding of colipase dependent lipase to the milk fat globule. Binding was efficient only in the presence of both fatty acid and colipase. We conclude that a limited gastric lipolysis of human milk triacylglycerol, resulting in a release of a low concentration of long-chain fatty acids, is of major importance for the subsequent hydrolysis by colipase-dependent lipase in the duodenum. PMID- 2917154 TI - Aspects of secondary and quaternary structure of surfactant protein A from canine lung. AB - The results of a large number of studies indicate that pulmonary surfactant contains a unique protein whose principal isoform has a molecular weight of about 30,000, and whose presence in surfactant is associated with important metabolic and physicochemical properties. This protein, SP-A, as isolated from canine surfactant, contains a domain of 24 repeating triplets of Gly-X-Y, similar to that found in collagens. These studies were undertaken to determine whether SP-A forms a collagen-like triple helix when in solution, and to describe certain aspects of its size and shape. Our experiments were done on SP-A extracted by two different methods from canine surfactant, and on SP-A produced by molecular cloning. The results from all three preparations were similar. The circular dichroism of the complete protein was characterized by a relatively large negative ellipticity at 205 nm, with a negative shoulder ranging from 215 to 230 nm. There was no positive ellipticity, and the spectrum was not characteristic of collagen. Trypsin hydrolysis resulted in a fragment with peak negative ellipticity at about 200 nm, without the negative shoulder. Further hydrolysis of this fragment with pepsin resulted in a CD spectrum similar to that of collagen. The spectrum of the collagen-like fragment was reversibly sensitive to heating to 50 degrees C, and was irreversibly lost after treatment with bacterial collagenase. SP-A migrated on molecular sieving gels with an equivalent Stokes radius of 110 to 120 A, and had a sedimentation coefficient of 14 S. Using these data we calculate a molecular weight of about 700,000. The hydrodynamic characteristics can be approximated as a prolate ellipsoid of revolution having an axial ratio of about 20. We conclude that SP-A aggregates into a complex of 18 monomers, which may form six triple-helices. The shape of the complex is considerably more globular than collagen and is not consistent with end-to-end binding of the helices to form fibrous structures. PMID- 2917155 TI - Evidence for critical-period programming of intestinal transport function: variations in the dietary ratio of polyunsaturated to saturated fatty acids alters ontogeny of the rat intestine. AB - 2-week isocaloric modifications in the dietary ratio of polyunsaturated/saturated fatty acids (P/S) alters intestinal transport in rats. This study was undertaken to test the hypotheses that (1) the fatty acid composition of a nutritionally adequate diet in early life has lasting consequences for active and passive intestinal transport processes; and (2) early life feeding experiences with diets of varying fatty acid composition influence the intestines' ability to adaptively up- or down-regulate intestinal transport in later life. Female Sprague-Dawley rats were weaned onto S or P and were maintained on these diets for 2, 10 or 12 weeks. An in vitro uptake technique was used in which the bulk phase was vigorously stirred to reduce the effective resistance of the intestinal unstirred water layer. P decreased and S increased the uptake of glucose, and this effect was progressive from 2 to 12 weeks. Switching from a P to an S diet decreased jejunal but increased ileal uptake of glucose, whereas switching from an S to a P diet was associated with a decline in both the jejunal and the ileal uptake of glucose. The ileal uptake of galactose increased as the animals grew on either P or S. Switching from P to S resulted in a decline in ileal uptake of galactose, whereas the opposite effect was observed when switching from S to P. The effect of feeding P or S on hexose uptake was influenced by the animals' dietary history: ileal glucose and galactose uptake was lower in animals fed P at an early age (PSP) than in animals fed P for the first time in later life (SSP). Jejunal glucose and galactose uptake was also lower in animals fed S at an early age (SPS) than in those fed S for the first time in later life (PPS). The alterations in the uptake of long-chain saturated and unsaturated fatty acids and cholesterol did not progress with longer periods of feeding, and in the jejunum, lipid uptake did not change when switching from P to S or S to P. Early feeding with P (PSP vs. SSP) was associated with lower jejunal uptake of 18:3 and lower ileal uptake of 12:0, whereas previous feeding with S (SPS vs. PPS) was associated with lower ileal uptake of cholesterol. The changes in uptake of hexoses and lipids was not explained by differences in the animals' food consumption, body or intestinal weight or mucosal surface area.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2917156 TI - Mechanism of the hypertriglyceridemia induced by tumor necrosis factor administration to rats. AB - 4 h after intravenous injection of recombinant HuTNF-alpha to fed rats, an increase in heart, diaphragm, and plasma lipoprotein lipase activity was observed. At the same time, a 40-60% decrease in enzymic activity in epididymal fat pad and kidney and 40% decrease in hepatic lipase activity in liver had occurred. Similar results were obtained 20 h after injection of recombinant HuTNF alpha into fasted rats. Pretreatment with Indomethacin did not affect the changes in tissue lipoprotein lipase activity observed following recombinant HuTNF-alpha administration. Serum triacylglycerol concentration increased by 2- and 6-fold; 4 and 20 h after recombinant HuTNF-alpha administration. Disappearance of 14C labeled triacylglycerol from the circulation after injection of small chylomicrons, biosynthetically labeled in their triacylglycerol and cholesterol moieties, was lower in TNF-treated than in control rats. However, the clearance rate of triacylglycerol was the same or even higher in recombinant HuTNF-alpha treated rats (assuming that 14C-labeled chylomicron triacylglycerol represents the serum triacylglycerol pool). The livers of recombinant HuTNF-alpha-treated rats and controls contained similar amounts of 14C-labeled lipids, but less [3H]cholesterol, suggesting that in recombinant HuTNF-alpha-treated rats, the liver took up chylomicron remnant particles enriched with triacylglycerol. Separation of the d less than 1.04 g/ml fraction of serum obtained from control and recombinant HuTNF-alpha treated rats by zonal ultracentrifugation revealed that in recombinant HuTNF-alpha-treated rats the lipoprotein particles were less lipolyzed than in controls. The secretion rate of [3H]triacylglycerol into the serum was determined 90 min after injection of [3H]palmitate albumin complex and Triton WR 1339. In recombinant HuTNF-alpha-treated rats, the secretion of [3H]triacylglycerol into plasma was 48% higher than in controls. It is suggested that the increase in lipoprotein lipase activity of heart and diaphragm resulted from an indirect effect of TNF. It is concluded that the increase in serum triacylglycerol in the recombinant HuTNF-alpha-treated rats is due mainly to an increased secretion of triacylglycerol by the liver. Impaired lipolysis, probably due to a fall in hepatic lipase could also contribute to the rise in plasma triacylglycerol. PMID- 2917157 TI - Reversal of quinone-induced chlorophyll fluorescence quenching. AB - We have used two methods to investigate the reversibility of the interaction of substituted quinones with the thylakoid membrane of plant chloroplasts. Treatment of chloroplasts with added quinones lowers the room-temperature Photosystem II chlorophyll fluorescence intensity by variable amounts depending on the identity and concentration of the quinone. The extent of restoration of the chlorophyll fluorescence level is used as a measure of the effectiveness of the reversal technique. One reversal method involves the addition of thiols to quinone-treated chloroplasts to alter the quinone in a chemical way via a nucleophilic 1,4 Michael addition. In general, the modified quinones exhibit a lower affinity for the thylakoid membrane, as evidenced by an accompanying increase in chlorophyll fluorescence. The thiol concentrations necessary for quenching reversal are found to be in the order [dithiothreitol] less than [2-mercaptoethanol] less than [glutathione]. The second reversal method examines the extent to which added quinones can be removed from thylakoid membranes using a concentration gradient established by resuspension of quinone-treated chloroplasts in quinone-free media. The results further support the reversible nature of the quinone inhibition and indicate that the extent of recovery is dependent upon the degree of fluorescence inhibition originally induced by the added quinone. PMID- 2917158 TI - Phosphate transport protein of rat heart mitochondria: location of its SH-groups and exploration of their environment. AB - (1) The properties of the SH groups of the phosphate transport protein of rat heart mitochondria were investigated on the basis of inhibition caused by SH reagents under different conditions. (2) The essential thiol groups are located near the external surface, as they are accessible to impermeable reagents from the external space. (3) The environment of the sulfhydryl groups influences their reactivity, as alteration of the external pH affects adversely their reactions with ionizable and non-ionizable SH reagents. (4) Intramitochondrial pH exerts a transmembrane effect: alkalinization augments and acidification diminishes the reaction rate of the sulfhydryl groups on the opposite surface of the membrane. (5) Changes of the concentration of the transported substrate occurring exclusively in the extramitochondrial space do not influence the reactivity of the essential SH groups. (6) It is concluded that in transport studies the phosphate transport protein of heart and liver mitochondria show basic similarity. It is suggested that the amino-acid sequence around the NEM-reactive cysteine (i.e., Lys-41 - Cys-42 - Arg-43) does not participate in substrate binding. PMID- 2917159 TI - Effect of lipid-protein interaction on the color of bacteriorhodopsin. AB - Detergent solubilization and subsequent delipidation of bacteriorhodopsin (bR) results in the formation of a new species absorbing maximally at 480 nm (bR480). Upon lowering the pH, its absorption shifts to 540 nm (bR540). The pK of this equilibrium is 2.6, with the higher pH favoring bR480 (Baribeau, J. and Boucher, F. (1987) Biochim. Biophysica Acta, 890, 275-278). Resonance Raman spectroscopy shows that bR480, like the native bR, contains a protonated Schiff base (PSB) linkage between the chromophore and the protein. However, the Schiff base vibrational frequency in bR480, and its shift upon deuteration, are quite different from these in the native bR, suggesting changes in the Schiff base environment upon delipidation. Infrared absorption and circular-dichroism (CD) spectral studies do not show any net change in the protein secondary structure upon formation of bR480. It is shown that deprotonation of the Schiff base is not the only mechanism of producing hypsochromic shift in the absorption maximum of bR-derived pigments, subtle changes in the protein tertiary structure, affecting the Schiff base environment of the chromophore, may play an equally significant role in the color regulation of bR-derived pigments. PMID- 2917160 TI - Mechanism of spectrin degradation induced by phenylhydrazine in intact human erythrocytes. AB - The exposure of human erythrocytes to phenylhydrazine results in the degradation of both monomers of spectrin, a major cytoskeleton membrane protein. The degradative process, characterized by a loss of spectrin without the appearance of high-molecular-weight products, either under reducing conditions or not, is almost complete in 10 min when a 5% erythrocyte suspension is treated with 1 mM phenylhydrazine. Under these conditions, we found a loss of 62.3 and 48.5% for the alpha and beta monomer, respectively. A similar degradative extent was obtained when the membrane ghost plus cellular free extracts, were dialyzed, and the membrane ghost plus hemoglobin was exposed to 1 mM phenylhydrazine for 10 min. The presence of different proteinase inhibitors and effectors, such as EDTA, diethylenetriaminepentaacetic acid, EGTA, leupeptin, aprotinin, phenylmethylsulfonyl fluoride, pepstatin, Ca2+ and ATP plus Mg2+, in the membrane ghost plus cellular free extract system (undialyzed) did not affect the degree of the spectrin-degradative process induced by phenylhydrazine. In addition, a purified spectrin tetramer preparation exposed to 1 mM phenylhydrazine in the presence of hemoglobin was degraded to an extent comparable to that with intact cells. Our data suggest that the initial degradative step of spectrin induced by phenylhydrazine in intact erythrocytes may be ascribed more to a direct oxidative breakdown, probably involving main-chain cleavage and side-chain cleavage processes, than to an eventual proteolytic system. PMID- 2917161 TI - Thermotropic properties of mixtures of negatively charged phospholipids with cholesterol in the presence and absence of Li+ or Ca2+ ions. AB - Mixtures of cholesterol with dipalmitoylphosphatidylserine or phosphatidic acid were investigated by differential scanning calorimetry. As in mixtures of natural phosphatidylserine with cholesterol (Bach, D. (1984) Chem. Phys. Lipids 35, 385 392), also here phase separation of cholesterol at molar ratios of 2:1 (phospholipid:cholesterol) and below is observed. The limited solubility of cholesterol in negatively charged phospholipids is found to be independent of the nature of the acyl chain residues, and independent of whether the negative charge resides on both COO- and PO- groups (as in phosphatidylserine) or on PO- only (as in phosphatidic acid). The separate cholesterol phase is also seen by DSC in mixtures of natural phosphatidylserine or phosphatidic acid with cholesterol in the presence of Ca2+; and in phosphatidylserine/cholesterol mixtures in the presence of Li+, by DSC and X-ray diffraction. PMID- 2917162 TI - Characterization of sodium-dependent nucleoside transport in rabbit intestinal brush-border membrane vesicles. AB - The characteristics of uridine transport were studied in rabbit intestinal brush border membrane vesicles. Uridine was taken up into an osmotically active space in the absence of metabolism and there was no binding of uridine to the membrane vesicles. Uridine uptake was markedly enhanced by sodium, but showed no significant stimulation by other monovalent cations tested. Kinetic analysis of the sodium-dependent component of uridine flux indicated a single system obeying Michaelis-Menten kinetics (Km value of 6.4 +/- 1.4 microM with a Vmax of 9.1 +/- 3.6 pmol/mg protein per s as measured under zero-trans conditions with a 100 mM NaCl gradient at 24 degrees C). A variety of purine and pyrimidine nucleosides were able to inhibit sodium-dependent uridine transport, suggesting that these nucleosides are also permeants for the same system. Consistent with this suggestion was the finding that these nucleosides also stimulated uridine efflux from the brush-border membrane vesicles. The sodium: uridine coupling stoichiometry was found to be 1:1 as measured by the activation method. From these results it is concluded that a broad specificity sodium-dependent nucleoside transporter is present at the brush-border membrane surface of rabbit enterocytes. PMID- 2917163 TI - Orientation of alpha-helical peptides in a lipid bilayer. AB - Samples of pure lipid (dipalmitoylphosphatidylcholine) and lipid containing short alpha-helical peptides were oriented and examined by X-ray diffraction, together with unoriented samples of pure peptide. X-ray reflections from the bilayer and the alpha-helices showed that the peptides had oriented in the bilayer with their helical axes perpendicular to the surface. PMID- 2917164 TI - Differences in membrane properties between unfertilised and fertilised single rabbit oocytes demonstrated by electro-rotation. Comparison with cells from early embryos. AB - The apparent membrane capacity of tubular rabbit oocytes increases from 1.7-2.0 microF/cm2 before fertilisation to 3.7-4.0 microF/cm2 after fertilisation. The membrane conductivity measured on single cells was also increased by fertilisation from less than 1 mS/cm2 to 14 mS/cm2. Cells obtained from 2-, 4- or 8-cell embryos exhibited intermediate values of membrane capacity (2.3-2.8 microF/cm2) and conductivity (5-22 mS/cm2). The values quoted are those effective between 1 and 10 kHz, the frequency of the rotating field used. The large apparent capacities are probably due to the presence of structures such as microvilli which cause the actual membrane area to exceed the smooth sphere area. It must be assumed that these structures change in form or number on fertilisation, and that they persist in embryos, at least up to the 8-cell stage. No difference was apparent between cells fertilised in vitro or in vivo. Comparison of the above zona-free data with measurements on zona-complete oocytes indicate how fertilised and unfertilised rabbit eggs may be distinguished from one another, even in the presence of the zona pellucida. PMID- 2917165 TI - Concentration effects on reactions in membranes: rhodopsin and transducin. AB - The reaction rate of two laterally-diffusing species in a biological membrane shows a maximum at some concentration of reactants, because an increase in the concentration of reactants tends to increase the reaction rate by the law of mass action but decreases the diffusion rate of the reactants. The activation of transducin by rhodopsin in the disk membrane of the rod outer segment is described in terms of a steady-state diffusion model with concentration-dependent diffusion coefficients. The optimum concentrations of reactants are obtained from contour plots of the reaction rate as a function of rhodopsin and transducin concentrations, and the sensitivity of the results to the assumed values of the variables is examined. To determine whether the observed concentrations are in fact those yielding the maximum reaction rate, several variables must be known more accurately. PMID- 2917166 TI - Interaction of inhibitin with the human erythrocyte Na+(Li+)i/Nao+ exchanger. AB - The kinetic interactions of inhibitin, a peptide isolated from cultured leukaemic promyelocytes, with erythrocyte Na+/Na+ and Na+/Li+ exchanges have been investigated. Inhibitin (1 microM) reduced the ouabain- and bumetanide-resistant sodium efflux and influx by equivalent amounts indicating an inhibitin-sensitive exchange component of 0.52 mmol/l per h. This value was not significantly different from that measured as the difference in sodium-rich (140 mM) and sodium free media (0.49 mmol/l per h). Similarly, the inhibitin-sensitive lithium efflux was equivalent to the sodium/lithium countertransport component (0.36 vs. 0.34 mmol/l per h), indicating that both exchanges were mediated by the same transport process, which is inhibitin-sensitive. The dose-response curve revealed the presence of a single inhibitin binding site per exchanger with a Ki of 2.10(-7) M. In kinetic inhibition studies, inhibitin (0.1 microM) decreased the Vmax of ouabain- and bumetanide-resistant sodium efflux with no effect on the Km for external sodium, i.e., inhibitin displayed a non-competitive mechanism of action. These findings indicate that inhibitin interacts with the Na+(Li+)i/Nao+ exchanger at a site distinct from the sodium binding site. PMID- 2917167 TI - Hydrophobic erythrocyte folate binding proteins are converted to hydrophilic forms by trypsin in vitro. AB - Human erythrocyte membranes contain high-affinity folate-binding proteins (FBPs) which on solubilization with detergents resolve into apparent 160,000 Mr moieties on Sephacryl S-200 gel filtration in Triton X-100. These FBPs share antigenic and ligand binding characteristics with particulate FBPs from other human tissues. During studies to define the vectorial orientation of these FBPs on the erythrocytes, we trypsinized intact cells with 250 micrograms trypsin per ml packed cells and quantitatively analysed the remaining cell-associated FBPs as well as the products of proteolysed FBPs in the supernatant. Incubation of intact cells with trypsin resulted in a dose-dependent decrease in their capacity to bind 125I-labelled pteroylglutamate (histamine derivative); at 250 micrograms/ml trypsin, folate binding was decreased by 77% compared to nontrypsin-treated control cells. While trypsinized cells contained proportionately lower quantities of apparent 160,000 Mr FBPs than untreated control cells, the supernatant of trypsinized cells (soluble phase) contained a single species of Mr = 40,000 which retained folate binding capacity. The sum of FBPs in trypsin supernatant and trypsin-treated cells was 87% of that found in untreated cells. Analysis of solubilized particulate erythrocyte FBPs and soluble (trypsin product) FBPs by sucrose density gradient ultracentrifugation in H2O and 2H2O above the critical micellar concentration of Triton X-100 revealed that apparent 160,000 Mr FBPs were detergent-binding (hydrophobic) species (which sedimented at Mr = 40,000 in H2O) while soluble FBPs (also sedimenting at Mr = 40,000) were hydrophilic and did not bind Triton X-100. These are the first data which show that hydrophobic FBPs can be directly converted to hydrophilic FBPs by a trypsin-mediated proteolytic event. The trypsin-sensitive site is likely to be at the junction between the detergent-binding site and the major body of the protein (Mr = 40,000) containing the folate binding site. PMID- 2917168 TI - Effects of free fatty acids and transition temperature on the stability of dry liposomes. AB - Previous studies have shown that liposomes composed of phospholipids with low phase-transition temperatures can be stabilized in the absence of water, provided that fusion is inhibited between the vesicles during drying, and that during rehydration the phospholipids do not pass through the gel to liquid crystalline phase transition. These conditions are met by adding certain disaccharides to the vesicles before drying, which inhibit fusion and depress the transition temperature in the dry lipids. The present study shows that preservation can also be achieved with vesicles made from dipalmitoylphosphatidylcholine (DPPC), but that the retention of trapped solute by such vesicles is much less than in vesicles composed of more fluid phospholipids. Addition of free fatty acids to the vesicles before drying destabilizes them; DPPC vesicles containing 15 mol% or more of palmitic acid leaked all their contents during drying, regardless of how much of the stabilizing sugar was added. Unlike the case for more liquid phospholipids, the leakage in DPPC vesicles is due solely to fusion and not to hydration-dependent phase transitions. Addition of free fatty acids results in increased fusion, leading to leakage. PMID- 2917169 TI - Glutamine transport by rat basolateral membrane vesicles. AB - Glutamine, a neutral amino acid, is unlike most amino acids, has two amine moieties which underlies its importance as a nitrogen transporter and a carrier of ammonia from the periphery to visceral organs. The gastrointestinal tract utilizes glutamine as a respiratory substrate. The intestinal tract receives glutamine from the luminal side and from the arterial side through the basolateral membranes of the enterocyte. This study characterizes the transport of glutamine by basolateral membrane vesicles of the rat. Basolateral membranes were prepared by a well validated technique of separation on a percoll density gradient. Membrane preparations were enriched with Na+/K+-ATPase and showed no 'overshoot' phenomena with glucose under sodium-gradient conditions. Glutamine uptake represented transport into the intravesicular space as evident by an osmolality study. Glutamine uptake was temperature sensitive and driven by an inwardly directed sodium gradient as evident by transient accumulation of glutamine above the equilibrium values. Kinetics of glutamine uptake under both sodium and potassium gradients at glutamine concentrations between 0.01 and 0.6 mM showed saturable processes with Vmax of 0.39 +/- 0.008 and 0.34 +/- 0.05 nmol/mg protein per 15 s for both sodium-dependent and sodium-independent processes, respectively. Km values were 0.2 +/- 0.01 and 0.55 +/- 0.01 mM, respectively. pH optimum for glutamine uptake was 7.5. Imposition of negative membrane potential by valinomycin and anion substitution studies enhanced the sodium-dependent uptake of glutamine suggesting an electrogenic process, whereas the sodium-independent uptake was not enhanced suggesting an electroneutral process. Other neutral amino acids inhibited the initial uptake of glutamine under both sodium-dependent and sodium-independent conditions. We conclude that glutamine uptake by basolateral membranes occurs by carrier-mediated sodium dependent and sodium-independent processes. Both processes exhibit saturation kinetics and are inhibited by neutral amino acids. The sodium-dependent pathway is electrogenic whereas the sodium-independent pathway is electroneutral. PMID- 2917170 TI - Thermodynamic and kinetic studies on the association of melittin with a phospholipid bilayer. AB - Association of the amphiphilic peptide melittin with unilamellar vesicles of dioleoylphosphatidylcholine has been experimentally investigated by means of circular dichroism, fluorescence energy transfer and stopped-flow experiments. Circular dichroism changes upon titration of the peptide with vesicles (at low salt concentration) were analyzed to yield thermodynamic association isotherms. These isotherms are quantitatively interpreted in terms of a monomer-monomer partitioning of melittin between the aqueous and bilayer media. The data can be very well fitted by theoretical curves based on a Gouy-Chapman surface potential. Energy transfer involving chemically modified tryptophan confirms a lack of aggregation of the associated peptide. According to the kinetic measurements the association proceeds in practice as a one-step process, which is rather fast but not fully diffusion-controlled. We propose a simple mechanism where the inherent conformational transition determines the overall rate. PMID- 2917171 TI - Characteristics of Na+-dependent hexose transport in OK, an established renal epithelial cell line. AB - The characteristics of Na+-dependent hexose uptake were determined for monolayers of OK, an established renal epithelial cell line derived from an opossum kidney. A comparison is made with other cultured cells, particularly LLC-PK1. The capacity to accumulate alpha-methyl D-glucoside (AMG) in OK cells develops with time, reaching a maximum level of 18 nmol/mg protein per h, 3 days after confluency. In contrast to LLC-PK1, this level is not influenced by the medium D glucose concentration. AMG uptake in OK cells was characterized by an apparent Km of 2.9 mM and a Vmax of 17.1 nmol/mg protein per min. For Na+-dependent phlorisin binding, a KD of 0.025 microM and a Bmax of 1.5 pmol/mg protein were found. A turnover frequency of 158/s was derived from our data. The hexose carrier of OK shares with the carrier of LLC-PK1 a high level of expression, its substrate specificity and turnover frequency. It differs however with respect to the substrate binding site. The affinity for AMG and D-glucose is 3- and 10-fold lower, whereas the affinity for phlorizin is 3-times higher in OK than in LLC PK1. The Na+ dependence of AMG uptake was also different for both cell lines and suggested for OK cells a 1:1, Na+:substrate stoichiometry. In OK cells, the phlorizin-sensitive uptake rate of D-glucose is much lower than the one for AMG. Nevertheless, D-glucose interacts with the AMG binding site in a competitive way and with an affinity similar to AMG. This could indicate a malfunction of the carrier with D-glucose as a substrate at the level of the translocation step. PMID- 2917172 TI - 4-alkylidene oxazolones as substrates and inhibitors for sensitive assays of the normality of active sites and the catalytic properties of hydrolases. AB - The suitability of eleven 4-alkylidene oxazolones for the determination of four hydrolases, alpha-chymotrypsin, trypsin, carboxylesterase and leucine aminopeptidase, was tested. The specific activities were in general low compared with those obtained with the classical substrates but the Kmapp values were also small. Hence, the kcat/Kmapp ratios of the oxazolones, the optimal indicator of activity, remained in the usual range. The high differential absorption coefficients of the oxazolones in the UV range render these substrates very suitable for the determination of active site normalities if the solubilities of the acyl enzymes and the magnitudes of the rapid bursts are sufficient. Since some of the oxazolones fluoresce, the sensitivity of the method may be increased up to 1000 x by fluorescence detection. The titrations may be carried out in organic solvents, e.g. dimethyl sulphoxide, which greatly stabilize the hydrolases. The high specificity of the oxazolones permits active site titrations in the presence of other hydrolases. PMID- 2917173 TI - Relationships between chemical structure and inhibition of ADP-stimulated human thrombocyte release of serotonin and platelet factor 4. AB - The inhibitory potencies of carbamoylpiperidinoalkane and N alkylnipecotoylpiperazine derivatives on ADP-stimulated human blood platelet aggregation, serotonin (5-HT) release and platelet factor 4 (PF-4) release were evaluated. The procedure was designed to allow concurrent determination of all three sets of values. Most compounds were more than twice as potent in blocking PF-4 (X = 91 +/- 1 (S.E., n = 7)%) compared to their inhibition of 5-HT (X = 38 +/- 1(S.E., n = 6)%) release; the one compound which failed to meet these criteria was still decidedly more powerful in impeding PF-4 than 5-HT release. Since the compounds' platelet aggregation-inhibitory values were within the same range as their 5-HT release-blocking potencies, but had a strikingly greater impact in arresting PF-4 release, it is suggested that the platelet plasma membrane and the lining enveloping the dense bodies may share certain commonalities, while the sheathing encasing the alpha-granules may differ from both in a tangible manner. PMID- 2917174 TI - A highly stable NADP-dependent isocitrate dehydrogenase from Thermus thermophilus HB8: purification and general properties. AB - NADP-dependent isocitrate dehydrogenase (EC 1.1.1.42) was purified to electrophoretic homogeneity from an extremely thermophilic bacterium, Thermus thermophilus HB8, and shown to be a dimeric protein of molecular weight 115,000, with a pI of 5.5. The amino acid composition of the present enzyme was similar to that reported for other bacterial counterparts, except for a high Arg/Lys ratio and a low Cys content. Divalent cations, such as Mn2+ and Mg2+, were essential for activity. The optimal pH was 7.8 at 55 degrees C. The Km values for NADP and D-isocitrate were 6.3 and 8.8 microM, respectively, with a Vmax of 77.6 mumol/min per mg at 55 degrees C. NAD was able to replace NADP with low efficiency. Backward reaction at 40 degrees C indicated that the Km value for 2-oxoglutarate was 63 microM with a Vmax of 4% that of the forward reaction at that temperature. The enzyme was highly stable against high temperature and denaturing reagents. PMID- 2917175 TI - Kinetic mechanism of Halobacterium halobium NAD+-glutamate dehydrogenase. AB - The kinetic mechanism of Halobacterium halobium NAD+-glutamate dehydrogenase (EC 1.4.1.3) has been investigated at pH 9.0, 3 M NaCl and 40 degrees C in both directions, by initial rate and inhibition studies. The results of the initial rate studies indicate that the mechanism is sequential with respect to substrate addition. The inhibition patterns obtained with halophilic NAD+-glutamate dehydrogenase are not consistent with a simple ordered mechanism without modification. They can, however, be reconciled with this type of mechanism by postulating an appropriate abortive complex. PMID- 2917176 TI - Purification and characterization of a novel calcium-dependent serine proteinase secreted from malignant hamster embryo fibroblast Nil2C2. AB - A novel serine proteinase was purified from the conditioned medium of malignant hamster embryo fibroblasts, Nil2C2. The molecular weight of the purified enzyme was estimated to be 88,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis under non-reducing conditions. The enzyme was split into two subunits (Mr 66,000 and 33,000) with a reducing agent. The enzyme hydrolyzed not only synthetic peptides which are susceptible to trypsin digestion but also extracellular matrix proteins such as type I and IV collagen, fibronectin and gelatin. For the digestion of these proteins, Ca2+ at millimolar concentrations was essential but Ca2+ or chelators did not affect the esterase activity for synthetic peptides. The proteolytic activity was inhibited by diisopropyl fluorophosphate (DFP) and also by phenylmethylsulfonyl fluoride. DFP was shown to bind to the 33 kDa subunit, indicating that the catalytic machinery of the enzyme is located in this subunit. PMID- 2917177 TI - Asymmetrically glycosylated IgG isolated from non-immune human sera. AB - When human IgG or its F(ab')2 fragment purified from a pool of non-immune sera was passed through a Con A-Sepharose column, 12% of the molecules bound to concanavalin A. While 44% of Fab' and 72% of Fd' fragments obtained from F(ab')2 retained by concanavalin A and eluted with methyl alpha-D-mannoside bound to concanavalin A, the Fab' and Fd' fragments obtained from non-retained F(ab')2 and the L chains and Fc fragments did not interact with the lectin. Only Fd' fragment obtained from the F(ab')2 retained by concanavalin A inhibited the fixation of guinea-pig erythrocytes to concanavalin A. These results are similar to those previously observed for IgG antibodies of different animal species and indicate that partial asymmetric glycosylation is a general phenomenon that is not restricted exclusively to IgG molecules with known specificity. PMID- 2917178 TI - Triplet state characteristics and singlet oxygen generation properties of anthracyclines. AB - The triplet states of adriamycin (Ad), daunomycin (D) and two daunomycin analogues, daunomycinone (Dc) and daunomycin N-trifluoroacetamide (DAc), have been studied using laser flash photolysis and pulse radiolysis techniques. Triplet lifetimes, molar absorption coefficients, energy levels and quantum yields have been obtained for Dc and DAc, and estimated for D and Ad. Time resolved near-infrared singlet oxygen luminescence measurements have been carried out on D, Ad and 5-iminodaunomycin (5-ID) in 2H2O solution and Dc in benzene solution at room temperature. Singlet oxygen quenching by the water-soluble anthracyclines was observed and a second-order rate constant of approx. 10(8) M 1.s-1 obtained. Electron spin resonance experiments have demonstrated that D photoexcited at lambda less than or 365 nm gives rise to singlet oxygen as shown by its reaction with 2,2,6,6-tetramethyl-4-piperidone to give the corresponding nitroxyl radical. Although all the anthracyclines studied have the ability to photosensitize the formation of singlet oxygen, the quantum yields are very low (phi delta approximately 0.02-0.03), suggesting that these anthracyclines would be poor photodynamic sensitisers. PMID- 2917179 TI - Detection of 2H-1,4-thiazine-5,6-dihydro-3,5-dicarboxylic acid (lanthionine ketimine) in the bovine brain by a fluorometric assay. AB - A new sulfur imino acid, 2H-1,4-thiazine-5,6-dihydro-3,5-dicarboxylic acid (lanthionine ketimine), has been detected in the bovine brain by means of fluorometric and HPLC procedures. The fluorometric assay is based on the fluorescent property of the copper-ketimine interaction product at pH 11.5. Other ketimines do not fluoresce in these conditions. The fluorophore exhibits an excitation maximum at 353 nm and an emission at 462 nm and is stable for at least 24 h. In the test conditions the fluorescence is proportional to the ketimine concentration from 1 to 200 microM. Detection of endogenous lanthionine ketimine has been performed after a simple enrichment procedure (brain deproteinization and extraction with diethyl ether) which minimizes degradative by-reactions of the unstable ketimine. The concentration of this new sulfur imino acid in the brain ranges from 0.5 to 1 nmol/g in three different samples. Identification and quantitations were confirmed by an HPLC procedure which takes advantage of the selective absorption at 380 nm of the phenylisothiocyanate-ketimine adduct. The identification of lanthionine ketimine in nervous tissues may have important metabolic and physiological implications. PMID- 2917180 TI - Rapid prenatal diagnosis of beta thalassemia using DNA amplification and nonradioactive probes. AB - We used in vitro DNA amplification by the polymerase chain reaction and nonradioactive probes for prenatal diagnosis of beta thalassemia in Chinese from the Guangdong province. Exact molecular diagnoses were made in all 20 fetuses studied over a 6-month period. We conclude that this method of prenatal diagnosis for beta thalassemia is a viable approach in many parts of the world where this disease is common. PMID- 2917181 TI - International Fanconi Anemia Registry: relation of clinical symptoms to diepoxybutane sensitivity. AB - Fanconi anemia (FA) is characterized clinically by a progressive pancytopenia, diverse congenital abnormalities and increased predisposition to malignancy. Although a variable phenotype makes accurate diagnosis on the basis of clinical manifestations difficult in some patients, study of cellular sensitivity to the clastogenic effect of DNA cross-linking agents such as diepoxybutane (DEB) has been used to facilitate the diagnosis. Data from DEB-induced chromosomal breakage studies of 328 peripheral blood specimens from patients considered at risk for FA were analyzed using a stepwise multivariate logistic regression, in order to determine which method of representing the data best discriminated between DEB sensitive (DEB+) and DEB-insensitive (DEB-) cases. Similar methods were applied to the data from the International Fanconi Anemia Registry (IFAR) to determine whether DEB+ and DEB- cases may be considered as distinct clinical entities, and if so, which variables provide the best discrimination between the two groups. We conclude that hypersensitivity to the clastogenic effect of DEB is a useful discriminator for FA. A simplified scoring method for classifying patients on the basis of eight clinical manifestations that are the best predictors for FA is presented. Our data indicate that the clinical diversity in FA is more widespread than previously recognized. PMID- 2917182 TI - Tiazofurin induction of mouse erythroleukemia cell hemoglobin production in the absence of commitment or changes in protooncogene expression. AB - Tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide, NSC 286193), is a synthetic nucleoside inhibitor of inosine monophosphate dehydrogenase and blocks guanine nucleotide biosynthesis. In the present study, we examined the effects of tiazofurin on mouse erythroleukemia (MEL) cell differentiation and protooncogene expression. Tiazofurin induced hemoglobin production in MEL cells in a concentration-dependent manner, as measured by an increase in benzidine staining. Northern blot analysis of MEL cells treated with 7 mumol/L tiazofurin demonstrated accumulation of both alpha- and beta-globin RNA transcripts. This induction of differentiation was blocked by the presence of exogenous guanosine (100 mumol/L). In contrast to the down-regulation of c-myc and c-myb RNA in MEL cells induced by dimethyl sulfoxide (DMSO) or hexamethylene bisacetamide (HMBA), there was no detectable change in levels of these transcripts after tiazofurin treatment. Furthermore, MEL cells induced by tiazofurin did not commit to terminal differentiation. These results suggest a role for guanine nucleotides, at least in part, in the regulation of MEL cell differentiation. PMID- 2917183 TI - Production of human factor IX in animals by genetically modified skin fibroblasts: potential therapy for hemophilia B. AB - Inherited diseases might be treated by introducing normal genes into a patient's somatic tissues to correct the genetic defects. In the case of hemophilia resulting from a missing clotting factor, the required gene could be introduced into any cell as long as active factor reached the circulation. We previously showed that retroviral vectors can efficiently transfer genes into normal skin fibroblasts and that the infected cells can produce high levels of a therapeutic product in vitro. In the current study, we examined the ability of skin fibroblasts to secrete active clotting factor after infection with different retroviral vectors encoding human clotting factor IX. Normal human fibroblasts infected with one vector secreted greater than 3 micrograms factor IX/10(6) cells/24 h. Of this protein, greater than 70% was structurally and functionally indistinguishable from human factor IX derived from normal plasma. This suggests that infected autologous fibroblasts might provide therapeutic levels of factor IX if transplanted into patients suffering from hemophilia B. By transplanting normal diploid fibroblasts infected with the factor IX vectors, we showed that human factor IX can be produced and is circulated at readily detectable levels in rats and mice. PMID- 2917184 TI - Inhibition and complexation of activated protein C by two major inhibitors in plasma. AB - To determine the major physiologic inhibitors of activated protein C (APC), plasma was incubated with APC or with Protac C and subjected to immunoblotting. APC:inhibitor complexes gave two major bands reacting with antiprotein C antibodies when immunoblotted on nondenaturing gels, and additional minor bands that varied between serum and plasma. Formation of one of the two major bands of APC:inhibitor complex, but not the other, was stimulated by heparin and only this band reacted with antibodies to the previously described APC inhibitor that is here designated PCI-1. Plasma immunodepleted of PCI-1 formed complexes with APC as visualized with antiprotein C but not anti-PCI-1 antibodies, and exhibited heparin-independent inhibition of APC activity, providing evidence for the existence of a second major physiologic APC inhibitor, PCI-2. Formation of APC:PCI-2 complexes in PCI-1-depleted plasma paralleled inhibition of APC amidolytic activity. PCI-2 was separated from PCI-1 and partially purified using column chromatography. PCI-2 formed inactive complexes of approximately 110,000 molecular weight (mol wt) with APC suggesting PCI-2 has an approximate mol wt of 50,000. Thus, inhibition of APC in plasma involves two major distinct 50,000 mol wt inhibitors, the heparin-dependent PCI-1 and the heparin-independent PCI-2. PMID- 2917185 TI - The secretory release reaction initiated by complement proteins C5b-9 occurs without platelet aggregation through glycoprotein IIb-IIIa. AB - The secretory and aggregation responses of stirred platelets exposed to complement proteins C5b-9 was investigated. C5b-9 assembly on the platelet surface resulted in the release of dense granule adenosine triphosphate (ATP) accompanied by a decrease in sample turbidity, but no detectable cell lysis. Inhibition of cellular protein kinase C completely blocked the C5b-9 initiated release of ATP, confirming the secretory nature of this response. Addition of fibrinogen (up to 1 mg/mL) had no effect on either the release of ATP or the decreased turbidity observed for C5b-9 cells. Addition of the peptides Arg-Gly Asp-Ser (RGDS) and fibrinogen gamma-chain carboxyl-terminal (gamma 397-411) at concentrations sufficient to completely block fibrinogen binding to GP IIb-IIIa had no effect on either C5b-9 induced dense granule secretion or the associated turbidity change. Microscopic examination and electronic particle counting of the stirred platelet suspensions confirmed that no aggregation of C5b-9 platelets occurred even when these cells were stirred in the presence of fibrinogen. The capacity of the C5b-9 proteins to initiate platelet secretion without activation of cell surface glycoprotein (GP) IIb-IIIa suggests a mechanism for intravascular dissemination of activated platelets during complement activation in vivo. PMID- 2917186 TI - Formation of C1s-C1-inhibitor, kallikrein-C1-inhibitor, and plasmin-alpha 2 plasmin-inhibitor complexes during cardiopulmonary bypass. AB - Stimulation of platelets and neutrophils occurs during clinical cardiopulmonary bypass. We investigated whether the classical complement, contact, or fibrinolytic pathways are activated as potential sources of neutrophil agonists. Using enzyme-linked immunosorbent "sandwich" assays specific for C1s-C1-and kallikrein-C1-inhibitor complexes respectively, we found that there was a modest increase in plasma levels of each complex after clinical cardiopulmonary bypass was completed. The increased concentration of enzyme-inhibitor complexes reverted to baseline within 24 hours. Since these complexes are cleared in vivo, we measured their formation by assaying their plasma levels during in vitro simulated extracorporeal circulation. Over a period of two hours, C1s-C1 inhibitor complexes rose from a baseline of 2 +/- 1 nmol/L to 21 +/- 2 nmol/L, and kallikrein-C1-inhibitor complexes rose from 2 +/- 1 nmol/L to 25 +/- 5 nmol/L. However, there was no evidence of either in vivo or in vitro plasmin alpha 2-plasmin-inhibitor complex formation. These results indicate that the pathways of classical complement and contact activation, but probably not fibrinolysis, may be associated with neutrophil activation seen during clinical cardiopulmonary bypass. PMID- 2917187 TI - A form of protease nexin I is expressed on the platelet surface during platelet activation. AB - A protein that has several similarities to protease nexin I, a fibroblast thrombin and urokinase inhibitor, has been detected on platelets (Gronke RS, Bergman BL, and Baker JB: J Biol Chem 262:3030, 1987). On incubation of platelets with 125I-thrombin, this platelet protein forms complexes with 125I-thrombin that are found both in the incubation medium and, as demonstrated here, associated with purified platelet plasma membranes. The present results indicate that interaction with the platelet surface may modulate the conformation and function of this platelet form of protease nexin I (PNIp) because: (a) an antibody against protease nexin I inhibited released PNIp, but not platelet-bound PNIp from complexing 125I-thrombin, and (b) whereas PNIp extracted from platelets bound both thrombin and urokinase, platelet-bound PNIp bound only thrombin. In experiments using several different platelet isolation methods, PNIp accounted for a large fraction of the rapid high affinity binding of 125I-thrombin to platelets. However, platelets isolated and maintained in the presence of metabolic inhibitors failed to take added thrombin into 125I-thrombin-PNIp complexes. This finding suggests that PNIp is released from inside platelets during activation, and thus does not function to transmit the primary activating signal that is generated by thrombin binding to platelets. PMID- 2917188 TI - Identification of a cellular polypeptide that distinguishes between acute lymphoblastic leukemia in infants and in older children. AB - We analyzed the polypeptide pattern of leukemic cells of infants and older children with acute lymphoblastic leukemia (ALL), using two-dimensional polyacrylamide gel electrophoresis (PAGE). Patterns were analyzed for the occurrence of a previously detected cytosolic polypeptide, designated L3. Quantitative analysis of L3 in 12 infants and 91 older children with non-T ALL indicated lack of expression of polypeptide L3 in leukemic cells of infants which, in most cases, expressed HLA-DR and CD19 and lacked CD10. Quantitative analysis of L3 in relation to cell surface marker expression revealed that L3 was limited in its occurrence to non-T ALL and was not coordinately expressed with any of the surface markers included in the study. Among patients in the HLA-DR positive, CD19-positive, and CD10-negative group, different levels of polypeptide L3 were observed between infants and older children. These results indicate differences in leukemic cell constituents between infants and older children with ALL and an otherwise similar cell surface marker phenotype. PMID- 2917189 TI - Hematogones: a multiparameter analysis of bone marrow precursor cells. AB - Morphologically distinct lymphoid cells with homogeneous, condensed chromatin and scant cytoplasm can be observed in large numbers in the bone marrow of children with a variety of hematologic and nonhematologic disorders. In some patients, these cells may account for greater than 50% of the bone marrow cells, creating a picture that can be confused with acute lymphoblastic leukemia (ALL) or metastatic tumor. Although originally called hematogones (HGs), a variety of other names have been proposed for these unique cells. The clinical significance of expanded HGs has not been resolved, and the biologic features of these cells are incompletely described. In this study, we correlate the clinical, morphologic, cytochemical, flow cytometric, molecular, and cytogenetic properties of bone marrow samples from 12 children with substantial numbers of HGs (range 8% to 55% of bone marrow cells). Diagnoses in these patients included anemia, four; neutropenia, one; anemia and neutropenia, one; idiopathic thrombocytopenic purpura, two; retinoblastoma, two; Ewing's sarcoma, one; and germ cell tumor, one. Flow cytometric analyses of bone marrow cells demonstrated a spectrum extending from early B-cell precursors (CD10+, CD19+, TdT+, HLA-Dr+) to mature surface immunoglobulin-bearing B cells in these patients, corroborating our morphologic impression of HGs, intermediate forms, and mature lymphocytes. DNA content was normal, and no clonal abnormality was identified by either cytogenetic or immunoglobulin and T-cell receptor (TCR) gene rearrangement studies. Follow-up ranged from 3 months to 3 years. None of the patients has developed acute leukemia or bone marrow involvement by solid tumor. The possible role of HGs in immune recovery and hematopoiesis is presented. PMID- 2917190 TI - Identification of a leukocyte alloantigen with a high-frequency expression in leukemia patients. AB - In this report we describe the production and characterization of a monoclonal antibody to the human promyelocytic leukemia cell line HL-60. The antibody, NC-2, is of the IgG1 subclass and precipitates a 50-Kd protein from 125I-labeled HL-60 cells. The antigen is insensitive to treatment with trypsin, papain, or neuraminidase. NC-2 did not react with a number of established human cell lines, including Daudi, Molt-4, K562, U937, KG-1, CEM, Raji, and Gash-P. Neutrophils and monocytelike cells derived from HL-60 cells that were induced to differentiate continued to express the antigen. NC-2 reacted with all peripheral-blood cells except erythrocytes from eight (5%) of 150 normal individuals tested. Bone marrow samples from patients with myelogenous leukemias were more frequently reactive with NC-2 than were those from normal individuals (12/33 v 1/10). Family studies indicated that the antigen was inherited in an autosomal-dominant manner. These findings suggest that the expression of the above alloantigen is associated with an increased incidence of leukemia. PMID- 2917191 TI - Viscoelastic properties of red cell membrane in hereditary elliptocytosis. AB - The viscoelastic properties of the RBC membrane are in part determined by a submembrane network of proteins consisting of spectrin alpha beta heterodimers (SpD) assembled head-to-head to form spectrin tetramers (SpT) and spectrin oligomers (SpO). SpT, in turn, are connected into a two-dimensional network by the linkage of distal ends of SpT to protein 4.1 and actin. With the micropipette technique, we determined the membrane viscoelastic properties of RBCs from a subset of patients with hereditary elliptocytosis (HE); these RBCs exhibit membrane skeletal instability, defective SpD self-association, and a molecular defect in the alpha I domain of spectrin, which is involved in the SpD-SpD contact (HE SpD alpha-SpD). The elastic modulus and viscosity of the membrane were significantly higher for the HE RBCs than for the control cells. Incubation of normal cells with N-ethyl-maleimide (NEM) produced a similar defective SpD self-association and a significant increase in the viscoelastic parameters of the membrane. The data provide evidence that the mode of assembly of membrane spectrin in the cytoskeletal protein network plays a major role in determining the rheologic behavior of erythrocyte membrane. PMID- 2917192 TI - Characterization of the serum In(Lu)-related antigen: identification of a serum protein related to erythrocyte p80. AB - The In(Lu) gene has been shown previously to downregulate expression by erythrocytes and by a subset of leukocytes of an 80-Kd protein antigen defined by monoclonal antibody (MoAb) A3D8. A3D8 antibody has also been shown by inhibition studies to recognize a serum antigen; this serum antigen is present in reduced amount in serum from In(Lu) donors. The present study demonstrates that the serum antigen recognized by A3D8 antibody also resides on a protein similar in size to the protein present in erythrocyte membranes. Studies using chromatographically purified protein have further shown that this antigen shares many epitopes with that present in RBCs and is therefore likely to be extremely homologous or identical to the erythrocyte In(Lu)-related p80. PMID- 2917193 TI - Thalassemia intermedia resulting from a mild beta-thalassemia mutation. AB - We investigated the molecular basis for a mild phenotype in a group of patients with beta(+) thalassemia originating from Northern Sardinia by definition of the beta-thalassemia mutation, alpha-globin mapping and beta-globin haplotype determination. In nine patients, we detected the compound heterozygous state for the -87 promoter mutation and the codon 39 nonsense mutation; in one patient, we detected the combination of the codon 39 nonsense mutation and beta(+) IVS-1 nt 6 mutation. These patients were either nontransfusion dependent for survival or became transfusion dependent later. We did not detect the -87 promoter mutation in any of 115 thalassemia major patients originating from the same part of Sardinia, investigated as controls. Heterozygotes for the -87 promoter mutation showed statistically higher hemoglobin (Hb) levels and larger and better hemoglobinized RBCs as compared with heterozygotes for the codon 39 nonsense mutation. From these data, we conclude that the -87 promoter mutation is a mild thalassemia allele, able to produce a phenotype of intermediate severity even in combination with a beta(0)-thalassemia mutant. The coinheritance of alpha thalassemia or the -++-- 5' subhaplotype in several cases may have contributed to development of the mild clinical picture. Characterization of the beta thalassemia mutation in combination with alpha-globin mapping and haplotype analysis may allow a better estimate of the probability of a given clinical phenotype, thus permitting more accurate counseling. PMID- 2917194 TI - Inhibition of platelet-dependent thrombus formation by human activated protein C in a primate model. AB - The in vivo antithrombotic properties of human plasma activated protein C (APC), a natural anticoagulant enzyme, were investigated in a baboon model of thrombus formation on prosthetic vascular grafts. Infusion of 0.25 to 1.1 mg/kg/h purified, human, APC inhibited blood clotting, as measured by the activated partial thromboplastin time (APTT), and reduced vascular graft platelet deposition by 40% to 70%, as determined by the real-time scintillation camera imaging of 111In-labeled platelet deposition. APC infusion also preserved graft patency. Hemostatic plug formation remained normal, as measured by the template bleeding times. These results suggest that APC administration may produce immediate antithrombotic effects under arterial flow conditions. PMID- 2917195 TI - Procoagulant activity of endotoxin-treated human endothelial cells exposed to native human flowing blood. AB - It has been reported that cultured endothelial cells become procoagulant when exposed to endotoxin. This prompted us to investigate whether human endothelial cells treated with endotoxin could promote the generation of fibrin when exposed to human flowing blood. For this purpose we used a parallel-plate perfusion chamber in which confluent cultured endothelial cells from human umbilical veins were exposed for five minutes to directly drawn human nonanticoagulated blood, at wall shear rates of 100, 650, and 2600 sec-1. Fibrin deposition was assessed by morphometry. No fibrin deposition occurred on normal endothelial cells. In contrast, cells incubated with endotoxin for 4 or 18 hours induced fibrin deposition, but only at a shear rate of 100 sec-1. Since some extracellular matrix was exposed between the cells, we investigated whether extracellular matrix played a role in fibrin formation. When the endothelial cells incubated or not with endotoxin were removed by EDTA, the exposed extracellular matrix perfused with blood at 100 sec-1 supported platelet and fibrin deposition in both cases. This suggests that the effect of endotoxin on endothelial cells was not due to extracellular matrix alteration but only to cellular activation or secretion of procoagulant substances. We conclude that human endothelial cells treated with endotoxin can trigger fibrin formation and deposition at their surface when exposed to flowing blood at low shear rate. PMID- 2917196 TI - Two novel point mutations correlate with an altered developmental expression of blood coagulation factor IX (hemophilia B Leyden phenotype). AB - Hemophilia B Leyden is characterized by low levels of factor IX antigen and activity before the age of 15 years, whereas after puberty factor IX levels rise at a rate of about 5% per year. Two distinct point mutations (deletion of A, A--- G) were identified at position +13 of the factor IX gene of a Greek and an American patient with hemophilia B Leyden. The nucleotide changes have occurred 32 basepairs downstream of a previously reported point mutation in a Dutch kindred with the same hemophilic phenotype. The results point to the importance of sequences surrounding the putative start site for the constitutive expression of the factor IX gene and to the possible significance of an imperfect direct repeat of DNA. PMID- 2917197 TI - Monocyte long-term cultivation on microvascular endothelial cell monolayers: morphologic and phenotypic characterization and comparison with monocytes cultured on tissue culture plastic. AB - Human monocytes were cultured on monolayers of a newly established microvascular endothelial cell strain. As compared to monocytes cultured on plastic, these endothelium-"derived" monocytes (EDM) showed distinct morphology, higher motility, and different antigen-expression pattern for several surface markers, as detected by cytofluorimetry. The MO-1- and the Leu-M1-marker were maintained on EDMs while they were lost on plastic-cultured cells. The MAX 1-26-termed markers failed to increase on EDMs, in contrast to plastic-cultured monocytes. For seven additional markers, expression after two weeks in vitro was higher on EDMs than on plastic-cultured monocytes. Functionally EDMs showed typical monocyte/macrophage behavior and were easily removable from the culture system for further experimentation. Our data suggest that monocytes cultured on microvascular endothelial cells are maintained for several weeks in a more physiologic state than monocytes cultured on plastic. PMID- 2917198 TI - Abnormal peroxidase-positive granules in "specific granule" deficiency. AB - "Specific granule" deficiency (SGD) has been previously associated with lactoferrin deficiency. The antimicrobial peptides termed defensins, comprising 30% of normal primary granule proteins, have also been shown to be markedly deficient in SGD. The present study was undertaken to correlate these findings with ultrastructural morphometric analysis and peroxidase cytochemistry. Peroxidase-positive, rim-stained, large, defensin-rich dense granules, previously described as a subpopulation of azurophil or primary granules in normal neutrophils, were markedly decreased in a patient with SGD. Morphometric studies of peroxidase-positive granules indicated an average peroxidase-positive granule area (all profiles) in the patient of 0.019 +/- 0.017 micron 2 (mean +/- SD, n = 941) compared to control values from normal neutrophils of two volunteers of 0.049 +/- 0.033 micron 2 (n = 896) and 0.050 +/- 0.039 micron 2 (n = 873) (P less than 0.001 between patient and control samples). Granule histograms showed a single peak of small peroxidase-positive granules, whereas control samples contained more prominent subpopulations of larger peroxidase-positive granules. The total number of peroxidase-positive granules per 100 micron 2 of cytoplasm in the patient was 255 +/- 124 (mean +/- SD, n = 15 cell profiles), which was similar to control values of 266 +/- 63 and 212 +/- 109. Thus, the defensin deficiency in SGD is associated with a decrease in size rather than number of peroxidase-positive granules; suggesting that defensins contribute to normal peroxidase-positive granule size and that SGD is a more global granule deficiency than originally thought.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2917199 TI - Identical nucleotide sequences of the 3'A gamma globin gene enhancer elements from four different chromosomes. AB - We have determined the nucleotide sequence of the 2,360-bp long EcoRI fragment from four chromosomes; this fragment is located 3' to the A gamma globin gene and is considered to contain the enhancer element identified by Bodine and Ley. The chromosomes were from an Arabian sickle cell anemia patient with high Hb F and a homozygosity for haplotype No 31 and from a black sickle cell anemia patient with low Hb F and a homozygosity for haplotype No 19. A third chromosome carried the determinant for a nondeletional hereditary persistence of fetal hemoglobin seen in a Chinese subject, and the fourth was a normal chromosome from a Yugoslavian subject. Twenty-one differences were observed when a comparison was made with the published sequence; no differences were seen between the sequences of the four different samples except for an additional mutation in the Chinese. These data make it unlikely that specific mutations within this sequence are associated with increases in G gamma and A gamma production. PMID- 2917200 TI - G6PD Avenches and G6PD Moosburg: biochemical and erythrocyte membrane characterization. AB - Two new G6PD variants with severe enzyme deficiency in Switzerland (G6PD Avenches, G6PD I) and in Germany (G6PD Moosburg, G6PD II) are described. One patient had suffered from severe postpartal hyperbilirubinemia, the other one presented with chronic hemolysis and remittent hyperbilirubinemia. Both variants showed diminished electrophoretic mobility, both variants were heat labile. The Michaelis-Menten constants KM for glucose-6-phosphate and for NADP+ were normal. 2-Desoxy-glucose-6-phosphate was utilized by G6PD I in a higher and by G6PD II at a lower rate than by the normal enzyme. Desamino-NADP+ and galactose-6-phosphate were utilized by both variants at a normal rate. The electrophoretic separation of membrane proteins of G6PD II showed both in the presence and in the absence of 6-mercaptoethanol no difference concerning the formation of membrane protein aggregates between patient and normal control. PMID- 2917201 TI - Acute nonlymphocytic leukemia (M2) with chromosome abnormality trisomy 4 developing eight years after radiation therapy for breast cancer. AB - We report here the development, 8 years after radiation therapy for breast cancer, of acute nonlymphocytic leukemia (ANLL), type M2 of the FAB classification, in which trisomy 4 was detected as the only chromosomal abnormality. Simultaneous observation of cytologic and cytogenetic features of individual colonies derived from leukemic progenitor (L-CFU) and early progenitor (CFU mix) cultures in this patient revealed that all colonies examined had a normal karyotype, although the clone with trisomy 4 was predominant in the direct bone-marrow culture. These findings suggest that progenitor cells with trisomy 4 were less predominant in colony growth when stimulated by colony-stimulating factors (CSFs) than were stem cells with a normal karyotype. PMID- 2917202 TI - Bilateral tympanic cavity infiltration with effusion in a patient with acute myeloblastic leukemia. AB - A case of acute myeloblastic leukemia with bilateral tympanic cavity infiltration with effusion in addition to right facial and bilateral auditory nerve involvement is described. Tympanotomy demonstrated the presence of leukemic cells in the effusion of bilateral tympanic cavities. While repeated examinations of the cerebrospinal fluid using the cytocentrifuge failed to show any leukemic cells, it was suspected that the bilateral tympanic cavity infiltration was associated with meningeal involvement. PMID- 2917203 TI - Chorea in polycythemia vera: a rare presentation of hyperviscosity. AB - A 65-year-old woman developed severe chorea as the presenting symptom of the hyperviscosity syndrome together with polycythemia vera and an ovarian cyst. Whole blood viscosity was 69.5 centipoise at a shear rate of 1.1 s-1 (normal 12.0 22.0 centipoise). After four phlebotomies the chorea subsided completely, and the blood viscosity became normal. Hemoglobin level was stable at normal range and then increased to 18.0 g/dl with recurrence of the faciobuccal dyskinesia that disappeared promptly following the phlebotomies. This case emphasizes that in elderly patients with neurological disorders, such as chorea, polycythemia should be strongly considered as one of the treatable causes. PMID- 2917204 TI - Immunological phenotype of plasma cells in monoclonal gammopathy of undetermined significance. PMID- 2917206 TI - Journal interview 24. Conversation with Robert Straus. PMID- 2917205 TI - Monoclonal gammopathy in chronic myeloproliferative disorders. AB - The incidence of monoclonal gammopathy in 61 patients with chronic myeloproliferative disorders (CMPD) was studied. The distribution of patients among the CMPD subgroups was: chronic myelocytic leukemia, 24 patients; myelofibrosis, 11; polycythemia vera, 15; essential thrombocythemia, 7; unclassified MPD, 4 patients. Monoclonal gammopathy was found in 5 patients (8.2%). Two of these patients (1 IgA/k and 1 IgM/k) had myelofibrosis and 3 (2 IgG/k and 1 IgG/lambda) polycythemia vera. The presence of monoclonal gammopathy indicates an involvement of the lymphoplasmatic system in CMPD. PMID- 2917207 TI - Characteristics and help-seeking patterns of attenders at a community-based voluntary agency and an alcohol and drug treatment unit. AB - The assumption that clients using community-based facilities in the form of Councils on Alcohol have less serious alcohol problems uncomplicated by the physical, social and psychological difficulties found in those attending Alcohol Treatment Units was not confirmed. One of the most striking findings were the similarities, rather than the differences between the two samples. Both groups had attenders who were heavily dependent on alcohol and were experiencing a wide range of problems. Attenders at both agencies, women as well as men, had help seeking patterns similar to those described for other populations which were discontinuous and uncoordinated and featured multiple contacts and simultaneous use of different services. The need for co-ordination was discussed in the light of the improved outcome which can be expected given appropriate matching of clients to treatment. Some suggestions as to how this might be achieved were discussed. PMID- 2917208 TI - Lephetamine abuse and dependence: clinical effects and withdrawal syndrome. AB - Lephetamine (L-SPA) is a compound with central analgesic and anti-inflammatory action, recently reported to be abused in Italy. In this study, cases of L-SPA abuse were recorded. The survey included 15 patients who were assessed for effects caused by using L-SPA and induced by withdrawal. Moreover L-SPA was administered to 15 volunteers. L-SPA displayed effects partly similar to opiates and its withdrawal caused both subjective and objective symptoms. It is concluded that L-SPA exhibits abuse liability and dependence potential of a certain degree. PMID- 2917209 TI - Primary reconstruction of a major loss of lower jaw by an animal bite using a "rib sandwich" pectoralis major island flap. AB - A 20 weeks pregnant woman was bitten by a wild bear which took away the central portion of her jaw. A single stage primary reconstruction was performed using a composite pedicled pectoralis major "rib sandwich" island flap. This provided continence of the mouth, allowing her to feed herself within 3 weeks of the operation and to speak reasonably by 6 weeks. PMID- 2917210 TI - A new splint for use in axillary surgery. AB - The surgical options for the treatment of axillary hidradenitis suppurativa are discussed. A new light-weight splint is described which will allow comfortable immobilisation of the shoulder at 45 degrees yet permit full forearm movement and adequate access to the axilla for dressings. We have found the splint of benefit in the management of this conditions by promoting the primary healing of split skin grafts. PMID- 2917212 TI - Reconstruction of the middle-aged torn earlobe: a new method. PMID- 2917211 TI - Controlling the medicinal leech. AB - A simple method is presented for applying a medicinal leech (Hirudo medicinalis) to the precise area in which the clinician desires the leeching to take place. PMID- 2917213 TI - Squamous cell carcinoma of skin developing in a skin graft donor site. PMID- 2917214 TI - Computer-based coding of fractures in the craniofacial region. AB - A systematic approach to the coding of fractures in the craniofacial region is presented. An alpha-numeric code is formulated from an alpha component depicting the anatomical region of interest and a number which reflects the degree of disruption. PMID- 2917215 TI - Salvage of the ring avulsed finger in heavy manual workers. AB - Complete ring avulsion amputation (class III) injuries are difficult management problems, especially when they occur in heavy manual workers. By excising the bit of bone detached with the skin tube, opening up the skin tube into a flap and replanting it onto the proximal stump, two such cases were salvaged successfully, with early recovery of function. The fingers were shortened by 1.5 cm, had a normal nail, touch sensation and absence of cold intolerance and pain. Both of the patients returned to work in 4 months. PMID- 2917216 TI - The incidence of late recurrence (greater than 10 years); an analysis of 536 consecutive cases of cutaneous melanoma. AB - The main purpose of this study was, using a computerised database, to try to establish possible prognostic features shown in patients who develop late recurrence, after 10 years, from a melanoma. The records of 536 patients diagnosed and treated for cutaneous melanoma over a 10-year period were examined and 5 patients were found to have developed a late recurrence. These patients were all female and included both pre- and post-menopausal cases at the time of initial diagnosis. In 4 out of the 5 cases the primary lesion had been situated upon an extremity. This study adds to the evidence that prognostic indicators can lead to a possible identification of high risk patients and that the level of patient awareness and education must be maintained throughout the period of follow-up. PMID- 2917217 TI - Microvascular anastomoses in diabetes: an experimental study. AB - The process of intimal repair across a microvascular anastomosis has been studied in an animal model of diabetes using scanning electron microscopy. The mean area of re-endothelialisation at 10 days, 200 microns on either side of an experimental microarterial anastomosis, was 65% in nondiabetic controls compared to 16.5% in an untreated diabetic group and 10% in an insulin treated diabetic group. The degree of intimal repair was significantly lower in the diabetic groups compared to controls (p less than 0.01, Wilcoxon Rank Test). Defective re endothelialisation may contribute to anastomotic failure in clinical practice. PMID- 2917218 TI - Microarterial grafting into the carotid artery of the rabbit: some considerations concerning species-dependent thrombogenicity. AB - This study was undertaken to obtain more insight into the performance of microarterial prostheses in an experimental animal that resembles the human thrombogenically more closely than the rat. Therefore, microarterial polyurethane based (PU) prostheses and polytetrafluoroethylene (PTFE) prostheses were implanted into the carotid artery of the rabbit and were compared with regard to patency and thrombus formation at 1 hour (n = 4), 1 day (n = 4), 2 days (n = 4), 1 week (n = 4), 2 weeks (n = 6), 3 weeks (n = 6) and 6 weeks (n = 6) after implantation. Arterial autografts (n = 22), followed up for 2 weeks after implantation, served as a control for the surgical procedure. All arterial autografts were patent at the time of harvesting. In contrast, although all microarterial prostheses were patent at 1 hour and some were patent at 1 day, 2 days and 1 week, none of them were patent at 2, 3 and 6 weeks. The patent PTFE prostheses showed remarkably less thrombus accumulation on the graft surface when compared to the patent PU prostheses. However, all prostheses had the same amount of thrombus formation at the distal anastomosis. PMID- 2917219 TI - The Facial Appearance Sorting Test (FAST): an aid to the selection of patients for rhinoplasty. AB - A simple test which requires a few minutes to administer and score is described as an aid to the selection of patients for rhinoplasty. The sorting of cards evaluating appearance is performed consistently over a period of time by individual subjects and by different groups of subjects. A numerical formula is proposed which allows for deviation from the common system of evaluating appearance in measuring support for an application for rhinoplasty. PMID- 2917220 TI - A manoeuvre to locate the distal urethral opening at the tip of the glans in the final stage of Cecil-Culp urethroplasty. AB - One of the drawbacks of Cecil-Culp urethroplasty for hypospadias is its failure to place the distal urethral meatus at the tip of the glans when the scrotal flap is detached. This paper describes a manoeuvre to overcome this drawback with the help of a small flap from the median raphe of the scrotum at the third and final stage of Cecil-Culp urethroplasty. Relevant illustrations from a case and line drawings are included to describe the procedure. A small note is appended as a comment. PMID- 2917221 TI - Epithelioma cuniculatum plantare. AB - The clinical and histological findings and treatment of three patients with this well differentiated squamous cell carcinoma of the foot are presented. PMID- 2917222 TI - Silicone gel in the treatment of keloid scars. AB - Silicone gel is effective in the treatment of keloid scars. Eighteen patients with 22 scars were treated with gel and their progress reviewed at 6 months. Improvements in texture, colour and height of the lesions were noted. PMID- 2917223 TI - First branchial cleft sinus in hemifacial microsomia. AB - In this paper we present a case of first branchial cleft sinus in hemifacial microsomia. An external opening was placed about 2 cm infero-posterior to the microtic ear remnant. The literature is reviewed and discussed. PMID- 2917224 TI - Anomalous blood supply to the serratus anterior/rib composite flap. AB - The serratus anterior muscle and rib composite flap has been well described for oral and mandibular reconstruction. The flap may also be used in combination with the latissimus dorsi flap based on the common thoracodorsal vascular pedicle, a blood supply which has hitherto been proven to be reliable. This case demonstrates a totally independent arterial supply to the serratus anterior and latissimus dorsi muscles. PMID- 2917225 TI - How safe is it to give parenteral iron to a patient with rheumatoid arthritis (RA) and iron deficiency anaemia? PMID- 2917226 TI - 1H nuclear magnetic resonance investigation of synovial fluid components in osteoarthritis, rheumatoid arthritis and traumatic effusions. AB - The levels of a range of components were measured by 1H nuclear magnetic resonance (1H NMR) in samples of synovial fluid taken from three groups of patients: 10 with osteoarthritis (OA), 18 with rheumatoid arthritis (RA), and 11 with traumatic effusions. A large number of low molecular weight species were measured simultaneously in addition to triglycerides and glycoproteins. Large variations were found between individuals in any one disease group, and there was no measurable correlation between disease state and levels of any low molecular weight component. However, patients with traumatic effusions had high levels of saturated triglycerides, while those with OA had low levels. The chain length of the triglycerides found in OA synovial fluid appears to be shorter than that for the other groups. In RA the composition of triglycerides appears normal, while the overall level is slightly above normal. In a separate study, serial samples of synovial fluid drawn from the knees of two arthritic patients were examined, and the concentrations of glycoprotein, triglycerides and creatinine were found to show a reasonable correlation with each other and with systemic measures of disease activity. These data suggest the potential of synovial fluid triglycerides and creatinine as inflammatory markers. PMID- 2917227 TI - Fenestration of tenosynovial capillaries. AB - A proportion of superficial capillaries in joint synovium are known to be fenestrated. The specialized functions of these fenestrated capillaries are unknown. We report the finding of fenestrae in tenosynovial capillaries from rabbit peroneal tendon sheaths. Fenestrations occupied 0.66% of the endothelial surface. Fenestrated capillaries appear to be a general feature of synovium, rather than a specific feature of joint tissue. PMID- 2917228 TI - The effect of pregnancy on the onset of psoriatic arthritis. AB - Pregnancy may be a risk factor for the development of arthritis. The effect of pregnancy and other hormone-associated events on the expression of psoriasis and arthritis was investigated retrospectively in 33 female patients with psoriatic arthritis. Eighteen per cent of patients or 30% of mothers had onset of arthritis within 3 months postpartum. Another 5 patients (15%) had perimenopausal onset of arthritis. No such temporal association was seen with the onset of skin psoriasis. Hormone-associated events appear to be as important modifiers of the arthritis associated with psoriasis as they are for other forms of joint disease. PMID- 2917229 TI - The effect of continuing penicillamine and gold treatment on the course of penicillamine and gold nephropathy. AB - The effect of continuing penicillamine or gold treatment was examined in 53 patients with biopsy proven penicillamine (32) or gold (21) nephropathy. Thirty two patients stopped penicillamine or gold treatment as soon as proteinuria was detected whilst 21 patients continued treatment for periods of 2-11 months. The 24-hour creatinine clearance and urinary protein excretion were measured serially for a median period of 6 years. No significant differences were observed in the initial or maximum proteinuria, the duration of the proteinuria or in the initial or latest creatinine clearances between the groups of patients. These results indicate that penicillamine or gold treatment may be continued for short periods under close supervision despite moderate proteinuria without causing permanent renal damage. As several alternative non-nephrotoxic agents are available for the treatment of rheumatoid arthritis, continued treatment with penicillamine or gold despite proteinuria is seldom indicated. PMID- 2917230 TI - The patient is not a blank sheet: lay beliefs and their relevance to patient education. PMID- 2917231 TI - An unusual cause of joint swelling in rheumatoid arthritis. AB - We describe a patient with longstanding rheumatoid arthritis (RA) who developed a monoarticular swelling of the left elbow which proved to be due to non-Hodgkin's lymphoma (NHL) infiltration of skin and subcutaneous tissue. PMID- 2917232 TI - I recently saw a patient with a most unusual inflammatory arthritis of the knee. Deliberate self-harm was suggested by the general practitioner. How should I evaluate this possibility, and if necessary treat the problem? PMID- 2917233 TI - A controlled evaluation of arthritis education. AB - The benefits of patient education for those with chronic arthritis are well documented. Informed patients should practice self care more often, and may show reduced disability from their disease. An important question relates to maintenance of the knowledge and skills acquired in educational programmes. This prospective study evaluated an education programme for people with rheumatoid arthritis (RA) and osteoarthritis (OA). The intervention group participated in a comprehensively planned six session behaviourally based programme. A questionnaire was given to 100 patients and 95 matched but non-random controls before the programme, 1 month later, and at 3 and 12 months. The intervention group demonstrated improvements in knowledge, self-reported health behaviour and disability scores at 12 months, compared to the controls. No differences were reported in symptoms, compliance with therapy, pain perception, and locus of control. PMID- 2917234 TI - Rheumatoid arthritis and motor neurone disease--an association? AB - Three patients with rheumatoid arthritis and motor neurone disease are presented. The neurological syndrome supervened after 2, 19 and 23 years of polyarthritis and led to death within 4 years. The diagnosis of motor neurone disease was confirmed at post mortem in one case. Common immunological mechanisms may account for this previously unreported association. PMID- 2917235 TI - A case of lymphomatoid granulomatosis with a protracted course and prominent CNS involvement. PMID- 2917236 TI - Distillation. PMID- 2917237 TI - Frozen shoulder and cervical spine disease. PMID- 2917238 TI - Acute onset of scleroderma following subcapsular orchidectomy for carcinoma of prostate. PMID- 2917239 TI - Systemic lupus erythematosus and periodic peritonitis (FMF) PMID- 2917240 TI - Erythrocyte sedimentation rate as a parameter for drug evaluation in the MRL/l autoimmune mouse. PMID- 2917241 TI - Localized nodular myositis as the first manifestation of polymyositis. PMID- 2917242 TI - Osteomalacia and rheumatoid arthritis. PMID- 2917243 TI - Primary meningococcal arthritis caused by group A meningococcus: an unusual presentation of infection with an uncommon bacterial strain. PMID- 2917244 TI - Anaemia and rheumatoid arthritis. PMID- 2917245 TI - Rheumatoid arthritis and senile dementia of the Alzheimer's type. PMID- 2917246 TI - Surgeons and computers. PMID- 2917247 TI - Angelchik prosthesis. PMID- 2917248 TI - Gallbladder non-filling at ERCP. PMID- 2917249 TI - Postoperative wound pain. PMID- 2917250 TI - 'Sculpted' T tubes. PMID- 2917251 TI - Diagnosis and management of graft-enteric fistulae. PMID- 2917252 TI - Small bowel obstruction. PMID- 2917254 TI - Incisional hernias. PMID- 2917253 TI - Review of a hospital experience of breast abscesses. PMID- 2917255 TI - Femorofemoral bypass in unilateral iliac artery occlusion. AB - Between January 1973 and January 1988, 188 patients with unilateral iliac artery occlusion were treated at The Middlesex and University College Hospitals, 185 for primary disease and three for blockage of a previous aortobifemoral graft. In the early part of the series, a variety of operations, including aortofemoral and iliofemoral bypass, and endarteriectomy, was used. Femorofemoral bypass was at first reserved for patients who were considered unfit for major surgery, but the results seemed so good that it was adopted as the procedure of choice. Latterly, percutaneous transluminal angioplasty became available, and the role of this is discussed. Over the 15-year period, 150 patients underwent femorofemoral bypass (all but two receiving a prosthetic graft). Of these, 90 per cent had disabling claudication and 8 per cent had critical ischaemia. There were six early deaths (within 30 days of operation) and five late deaths, and two surviving amputees; nine patients could not be traced. The remaining 128 patients have been assessed at intervals of from 3 to 92 months, both clinically and with Doppler studies. The cumulative patency was 86 per cent at 13 years, and all of these patients experienced subjective and haemodynamic improvement in the recipient limb. Eight grafts occluded in the early postoperative phase. In five patients there was deterioration in the donor limb; it is postulated that the effect was due to causes other than the operation. There were two serious postoperative complications due to technical error, one of which led to early above-knee amputation. These are presented in detail. In the light of this experience, the advantages and indications for femorofemoral bypass and the results to be expected from it have become clarified, and the technique standardized so that errors can be avoided. We suggest that femorofemoral bypass is now the operation of choice for unilateral iliac artery occlusion. PMID- 2917256 TI - Risk of aortic aneurysm surgery as assessed by preoperative gated heart pool scan. AB - Gated heart pool scan measuring left ventricular ejection fraction (LVEF) was performed preoperatively in 72 patients presenting for elective repair of abdominal aortic aneurysm. Patients with a positive cardiac history were more likely to have a LVEF of less than or equal to 45 per cent (P less than 0.001). The operative mortality rate was 4 per cent. Each of three patients who died had a LVEF less than or equal to 35 per cent and developed cardiac failure which led to renal failure. Five other patients developed cardiac failure manifested by acute pulmonary oedema during the early postoperative period. There was no statistically significant association between a positive cardiac history and the occurrence of postoperative cardiac failure or death. However, patients with a LVEF of less than or equal to 45 per cent were more likely to develop postoperative cardiac failure (P = 0.004) while patients with a LVEF of less than or equal to 35 per cent had a greater chance of dying (P less than 0.001). No patient died with a LVEF greater than 35 per cent. Preoperative evaluation of LVEF can select patients at high risk of cardiac death from repair of abdominal aortic aneurysm. Such patients could be followed conservatively if they remain asymptomatic and the aneurysm does not enlarge. If operation is considered mandatory, patients with a low LVEF should receive intensive perioperative monitoring with enhancement of ventricular performance. PMID- 2917257 TI - Plasma arginine vasopressin levels and arterial pressure during open heart surgery. AB - A study of plasma arginine vasopressin (AVP) levels and their relation to changes in arterial pressure was undertaken in 13 patients undergoing open heart surgery. Seven of the patients received high doses of intravenous morphine (1 or 2 mg/kg) as part of their anaesthetic, whereas the other six did not. Increases in the AVP levels during cardiopulmonary bypass (CPB) were significant in both groups, but were significantly greater in the patients not receiving morphine (median 86.1 fmol/ml) than in those who did (47.5 fmol/ml). In both groups there was a linear correlation between the natural logarithm of the plasma AVP level and the percentage fall in the mean arterial pressure, although the slope of the relationship was significantly less in the group receiving morphine than in the group not receiving morphine. These results indicate that in patients undergoing cardiac surgery the neuroendocrine reflex control of plasma AVP levels in relation to changes in arterial pressure is intact, but that the sensitivity of the reflex (i.e. the increase in plasma AVP level for a given fall in arterial pressure) is reduced by the administration of high doses of intravenous morphine. PMID- 2917258 TI - Viscoelastic properties and collagen content of the long saphenous vein in normal and varicose veins. AB - Veins taken from patients undergoing surgery for varicose veins were compared with those obtained from patients undergoing other surgical procedures ('normals'). Varicose veins had a lower breaking strength and breaking energy than normal veins. Elastic stiffness was less in normals (tan theta = 41 (24] than in varicose veins (tan theta = 55 (18); P less than 0.01). There was no difference in viscoelastic behaviour between samples taken above, at, or below the valve leaflet insertion. In normals, perivalvular vein wall exhibited a 50 per cent lower breaking strength and elastic stiffness than vein from other sites. Collagen content was significantly higher in normal vein specimens in all sites examined (mean collagen content = 70 (21) micrograms/mg, versus 51 (20) micrograms/mg for varicose veins; P less than 0.001). We conclude that significant structural changes are seen in varicose veins. In normal veins, the perivalvular vein wall has distinct viscoelastic features when compared with vein wall from other sites. This difference was not found in veins which became varicose. PMID- 2917259 TI - Risk factors in onychocryptosis. AB - A study is described in which the normal toes of 50 patients with unilateral ingrowing toenails were compared with those of 50 healthy subjects matched for age and sex. Twenty-one potential risk factors were compared between the groups. All measurements on patients were derived from unaffected toes in order to avoid anatomical distortion due to the disease process. Statistical analysis revealed significant differences between the groups for three anatomical measures, namely nail fold width (P less than 0.001), medial rotation (eversion) of the great toe (P less than 0.02) and nail thickness (P less than 0.03). Possible discriminating variables were assessed using linear discriminant function analysis and a mathematical equation was derived based on these three factors. This equation was found to possess a potentially high predictive value in that it correctly classified 86 per cent of the patients and 77 per cent of the controls. A further group of 62 unselected patients presenting with unilateral onychocryptosis and 35 unaffected controls were assessed for these three parameters. Of these, 80 per cent of controls and 85 per cent of patients could be classified correctly by the equation. It is thus proposed that, in the majority of subjects with onychocryptosis, a discrete anatomical predisposition exists and that the other factors act only as triggers in the development of the condition. This study provides a rationale for less traumatic surgical approaches to ingrown nail than nail avulsion, with or without nail bed ablation and may also provide a means of identifying high-risk groups. PMID- 2917260 TI - Posterior sagittal anorectoplasty for reoperation in children with anorectal malformations. AB - A prospective study was carried out in 12 consecutive patients (7 boys and 5 girls), to evaluate posterior sagittal anorectoplasty for patients incontinent of faeces after anorectal reconstruction. Examination revealed anatomical problems such as: recurrent fistula (two), massive urethral diverticulum (one), absent vagina (one), and a missed urogenital sinus (one). Preliminary electromyography showed the external sphincter to be displaced from the anus in nine patients. Posterior sagittal anorectoplasty, with correction of anatomical defects and precise reconstruction of bowel within the sphincters, was carried out after the formation of a loop colostomy. No postoperative complications were observed. Contrast studies confirmed healed suture lines before stoma closure. Follow-up, between 4 and 46 months, revealed good faecal control in only two patients, with a significant improvement in two others. The rest remained incontinent although sensation was improved. These disappointing results, at variance with other published reports, lead us to conclude that posterior sagittal anorectoplasty, when used as a secondary procedure, is good for correcting anatomical defects but not for improving faecal continence. PMID- 2917261 TI - Anorectal function after abdominal rectopexy: parameters of predictive value in identifying return of continence. AB - Posterior abdominal rectopexy was performed in 12 patients with a full-thickness rectal prolapse: 9 had faecal incontinence. The prolapse was successfully controlled in all cases and six of nine patients were rendered continent. Physiological studies in patients were compared with age- and sex-matched controls. Preoperative anal pressures were significantly lower than in controls at rest (R), during maximum pelvic floor contraction (Sq) and attempted defaecation (St) (R, P less than 0.005; Sq, P less than 0.005; St, P less than 0.005). Anorectal angles were significantly more obtuse in patients than in controls (R, P less than 0.05; St, P less than 0.025). None of these parameters changed significantly after abdominal rectopexy. Median rectal emptying significantly decreased after operation (preoperative 83 per cent/min; postoperative, 58 per cent/min, P less than 0.05). Median perineal descent during attempted defaecation also significantly decreased after operation (preoperative, 8.5 cm; postoperative, 7.1 cm; P less than 0.025). Parameters which predicted return of continence included: delayed leakage during the saline infusion test (P less than 0.025), a narrow anorectal angle during pelvic floor contraction (P less than 0.025), minimal pelvic floor descent during contraction (P less than 0.05), and a long anal canal at rest (P less than 0.05) and during pelvic floor contraction (P less than 0.025). PMID- 2917262 TI - A study of the physiological variation in anal manometry. AB - The physiological variation in anal manometry using a perfused catheter with radiating sideholes was studied in 78 healthy volunteers. The maximum intraindividual variation in the length of the anal high pressure zone, resting pressure and squeeze pressure was 10 mm, 26 mmHg and 68 mmHg respectively. The median 95 per cent confidence interval for length of the pressure zone was 4 mm; for resting pressure it was 15 mmHg and for squeeze pressure it was 48 mmHg. Day to-day variation did not exceed the intraindividual variation. Constant recording with the catheter fixed in the high pressure zone revealed slow waves and ultraslow waves with amplitudes of 6-24 mmHg which could account for most of the intraindividual variation. No sex difference was found in the length of the high pressure zone whereas resting pressure and squeeze pressure were higher in men than in women. Although a tendency towards a decrease in the length of the high pressure zone, resting pressure and squeeze pressure was observed with increasing age, no significant age-related difference could be demonstrated. PMID- 2917263 TI - Treatment of cancer of the colon: a non-specialist's point of view. PMID- 2917264 TI - Air-filled microballoon manometry for use in anorectal physiology. AB - Manometry is fundamental to anorectal physiology but the water-filled manometric systems commonly used have several disadvantages. To investigate the 'new' air filled microballoon system, we compared it with a standard water-filled equivalent by measuring sphincter length, maximum resting pressure (MRP) and maximum voluntary contraction pressure (MVC) in 44 patients using the station pull-through technique. A good correlation was found for all three parameters (Spearman correlation coefficient rs: sphincter length = 0.86, MRP = 0.86 and MVC = 0.94, P less than 0.001). Repeat studies in 15 patients showed excellent reproducibility (rs: sphincter length = 0.97, MRP = 0.96 and MVC = 0.97, P less than 0.001). Air-filled microballoon manometry gives results similar to a water filled microballoon system and has many advantages. PMID- 2917265 TI - Pre-treatment with octreotide as an adjuvant to surgical resection in Zollinger Ellison syndrome. PMID- 2917266 TI - Near-total thyroidectomy for carcinoma of the thyroid. AB - There is controversy about the most appropriate treatment for patients with thyroid cancer. This study analyses our experience with 206 cases of thyroid cancer from an endemic goiterous area. There were 100 males and 106 females; patients presented at an earlier age with a short history. Thyroid cancers demonstrated an aggressive biological behaviour with an advanced stage at presentation (overt cancers in 51 per cent) and a relentless course with a mortality rate of 24.2 per cent for the well-differentiated tumours. Near-total thyroidectomy was performed in 126 patients. Multicentric foci of tumour were seen in 17.2 per cent of the well-differentiated cancers and 25.2 per cent of the cases of well-differentiated cancers who underwent near-total thyroidectomy developed loco-regional recurrence. Hemithyroidectomy was performed in 35 patients who refused completion total thyroidectomy at a second stage; 16.7 per cent of these patients developed a recurrence in the remaining contralateral lobe. Thus in our patients from an endemic goiterous area, near-total thyroidectomy is the treatment of choice particularly because of the frequent occurrence of follicular and anaplastic cancers (in 44.2 per cent) and because the course of the disease is more virulent. PMID- 2917267 TI - Contrast enhanced CT scan as a diagnostic procedure in mesenteric ischaemia due to mesenteric venous thrombosis. PMID- 2917268 TI - Facial paralysis due to a benign parotid tumour. PMID- 2917269 TI - Plunging salivary glands. PMID- 2917270 TI - Pseudoachalasia after radical gastrectomy. PMID- 2917271 TI - Heller's myotomy with partial fundoplication. PMID- 2917272 TI - Severe nonfluency in aphasia. Role of the medial subcallosal fasciculus and other white matter pathways in recovery of spontaneous speech. AB - The relationship between location and extent of lesion on CT scan and limitation in spontaneous speech was examined. The severity of spontaneous speech ranged from cases with no speech or only verbal stereotypies (first major group) to those with reduced, hesitant, poorly articulated, agrammatic speech (nonfluent Broca's aphasia, second major group). CT scan analysis revealed no single neuroanatomical area that contained an extensive lesion which could be used to discriminate the most severe cases from the least severe. The two groups were separable, however, on the basis of the CT scan when the extent of the lesion in two subcortical white matter areas were combined: (1) the most medial and rostral portion of the subcallosal fasciculus plus (2) the periventricular white matter near the body of the lateral ventricle, deep to the lower motor/sensory cortex area for the mouth. The most rostral portion of the medial subcallosal fasciculus, located in the lateral angle of the frontal horn (extremely deep to Broca's area), contains projections from the cingulate gyrus (area 24) and the supplementary motor area, to the caudate nucleus. We suggest that one explanation for the more severe limitation in spontaneous speech in the first group is the extensive white matter lesion in these two subcortical pathways had interrupted a large number of connections for (1) initiation and preparation of speech movements, and limbic aspects of speech (lesions in the medial subcallosal fasciculus), and (2) motor execution and sensory feedback for spontaneous speech (lesions in periventricular white matter deep to the motor/sensory cortex area for the mouth). Extensive lesion in only one of these two white matter pathway areas, alone was not sufficient to produce long-lasting severe limitation in spontaneous speech and could not be used to discriminate the two groups on the basis of the CT scans. The patients with less severe limitation in spontaneous speech (nonfluent Broca's aphasia) had less extensive lesion within these two white matter areas combined, and had interrupted a smaller number of these subcortical connections. The sites of the lesions in subcortical white matter in CT scans in Broca's original case who could only produce a verbal stereotypy are similar to those in our first group with the most severe limitation in spontaneous speech. The presence or absence of hemiplegia was not related to severity or recovery of spontaneous speech. Careful examination of lesion extent in these two areas of subcortical white matter on CT scanning appears to be relevant in predicting potential for recovery of spontaneous speech in some stroke patients. PMID- 2917273 TI - Hemisphere asymmetry for eye gaze mechanisms. AB - To investigate left/right asymmetries in cerebral gaze mechanisms, eye deviation was evaluated in 90 patients following intracarotid sodium amylobarbitone injections. For right-handed subjects with left cerebral language dominance, the occurrence and severity of eye deviation were greater for right versus left hemisphere injections. In contrast, subjects with mixed cerebral dominance for language/handedness exhibited no left/right difference in the incidence of eye deviation. The results are consistent with right cerebral dominance for attentional/intentional mechanisms directed at external space. Further analysis suggests that the cerebral asymmetry for gaze may be due to an evolutionary loss of attentional/intentional mechanisms by the left cerebral hemisphere as language function developed. PMID- 2917274 TI - Impairment and recovery of ipsilateral sensory-motor function following unilateral cerebral infarction. AB - After unilateral cerebral hemisphere stroke, resulting in contralateral arm symptoms but largely sparing higher cerebral function, ipsilateral arm function is generally considered to be unaffected. In this study, 8 subjects with acute unilateral cerebral infarction (confirmed by CT scan) and primarily motor deficits underwent 11 computerized and 6 clinical assessments between 11 days and 12 months poststroke, and were compared with 12 normal subjects. Computerized tests comprised 3 pursuit tracking tasks (preview-random, step and a combination of these), designed to measure different aspects of integrated sensory-motor (S M) function, and 12 tasks aimed at breaking tracking into various sensory, perceptual and motor components (joint movement sense, visual resolution, object perception, static and dynamic visuospatial perception, range of movement, grip and arm strength, reaction time, speed, static and dynamic steadiness). The asymptomatic arm was impaired on all but one of the computerized tests throughout the 12-month period, although to a lesser degree than the symptomatic arm. Grip strength was marginally impaired initially. Incomplete neurological recovery was seen in the asymptomatic arm for all functions except strength, speed and steadiness, possibly indicating their resistance to improvement. Clinical assessment detected no asymptomatic arm impairment and only a mild transient deficit of higher mental function. Our data suggest that (1) all cerebral hemisphere areas involved in S-M functions can exert some degree of bilateral motor control; (2) ipsilateral influence is never greater than contralateral influence, and is usually considerably less; and (3) the proportion of ipsilateral to contralateral control is closely related to the degree of continuous sensory feedback required by the particular task. The mechanism and degree of ipsilateral dysfunction can be explained by a 3-tier cerebral model of S-M integration comprising a lower level of functions with high contralateral specificity (somatosensory and motor), a middle level of non-limb-specific partially lateralized functions (ideomotor praxis and visuospatial perception) and an upper level of global mental activities (intellect, alertness, etc.). PMID- 2917275 TI - The natural history of multiple sclerosis: a geographically based study. I. Clinical course and disability. AB - The outcome of multiple sclerosis (MS), assessed according to the Kurtzke Disability Status Scale (DSS), was reviewed in 1,099 consecutive patients followed in London, Canada, between 1972 and 1984. A geographically based subgroup of 196 patients representing 90% of Middlesex County MS patients as well as a group of 197 patients seen from onset of disease were separately analysed. The clinical course was progressive from onset in 33% of the total population and in 28% of the Middlesex County subgroup. Of those with duration of 6-10 yrs, 30 40% with initially remitting disease developed progressive MS. The cross sectional distribution of disability was bimodal with peaks at DSS 1 (no disability) and DSS 6 (assistance required for walking). Actuarial analysis showed that the median time to reach DSS 6 from onset of MS was 14.97 +/- 0.31 yrs in the total population and 9.42 +/- 0.44 yrs in the "seen from onset' subgroup. Survival was minimally altered; 87% of patients followed up to 40 yrs were still alive, although ascertainment of cases with this duration of MS was incomplete. Data describing the rate at which disability develops after the onset of a progressive phase of MS are also presented. The implications of these data in planning and interpretation of clinical therapeutic trials are discussed. PMID- 2917276 TI - Changes in excitability of human cutaneous afferents following prolonged high frequency stimulation. AB - Prolonged high-frequency stimulation of cutaneous nerves can result in paraesthesiae that begin 20 to 30 s after the end of the train and last for 5 to 10 min. In the present experiments the effects of such stimulation on the excitability of human cutaneous afferents and on their refractory and supernormal periods were measured to determine whether these changes could explain the postactivation paraesthesiae. Attention was focused on the axons of lowest threshold (1.0-1.5 T) in the compound sensory action potential evoked by stimulating the digital nerves of the index or middle fingers. Repetitive activation produced two opposing effects on the excitability of low-threshold cutaneous afferents. Following stimulus trains of short duration (1-5 min) the dominant effect was a long-lasting decrease in excitability, such that the amplitude of a test afferent volley was always less than before stimulation. With these trains, no subject experienced paraesthesiae. For 10 min after stimulus trains lasting longer than 7 to 12 min the dominant effect was an increase in excitability such that the amplitude of the test volley was greater than before stimulation. Within this interval, following such trains, subjects experienced paraesthesiae. The extent and duration of supernormality induced by a supramaximal conditioning stimulus were greatly increased by stimulation for 1 min. Following stimulation for 10 min, the degree of supernormality of the enhanced test volley was much the same as before stimulation, but was inappropriately high for the size of the test volley. The sum total of the excitability change and the change in supernormality resulted in a larger potential after stimulation, whether the train lasted 1 min or 10 min. It is concluded that the postactivation changes in axonal excitability could predispose the most excitable axons to generate ectopic impulses and, thereby, to produce paraesthesiae. PMID- 2917277 TI - Diagnosis of unilateral telencephalic hearing disorders. Evaluation of a simple psychoacoustic pattern discrimination test. AB - A new psychoacoustic pattern discrimination test (PPDT) has been validated for the diagnosis of telencephalic hearing disorders. In this test, regular sequences of noise bursts or click trains are presented dichotically, and randomly occurring monaural changes in intensity or click pattern have to be discriminated. The PPDT was administered to 48 control subjects and to 62 patients with circumscribed cerebrovascular lesions. Involvement of telencephalic auditory structures (TAS) was assessed from CT scans. Abnormality in the PPDT was highly correlated with the incidence of a TAS lesion. The most prominent abnormality consisted of an increased error rate (missed discriminations) on the ear contralateral to the TAS lesion, comparable to the ear effect described for former dichotic tests. In normals, no ear dominance, which might have confounded the interpretation of lesion effects in patients, was observed for our test material. Also, the influence of peripheral hearing loss on test results was small. Criteria for the clinical evaluation of the PPDT were developed and yielded a good sensitivity (76.1%) when related to the CT scan data. Abnormality in the PPDT was also confirmed by reduced auditory evoked dipole source potentials in the lesioned hemisphere. Disturbances in auditory language comprehension in aphasic patients were not significantly related to a positive PPDT result, but a questionnaire about hearing difficulties revealed a close association of PPDT abnormality and auditory perceptual disturbances. These occurred only in difficult hearing environments, for example, the cocktail party situation. It must be concluded that unilateral TAS lesions lead to auditory perceptual impairment and communication problems, which should be given adequate attention during neuropsychological rehabilitation. PMID- 2917278 TI - X-linked recessive bulbospinal neuronopathy. A clinicopathological study. AB - A clinicopathological study on X-linked recessive bulbospinal neuronopathy was undertaken on 9 cases, with morphological observations on 3 autopsied cases and sural nerve biopsies from 6 patients. Both lower motor and primary sensory neurons were involved. Lower motor neurons were markedly depleted through all spinal segments and in brainstem motor nuclei except for the third, fourth and sixth cranial nerves. Primary sensory neurons were less severely affected. A quantitative study of primary sensory axons at several levels in the peripheral nervous system suggested that a distally accentuated axonopathy was the salient pathological process. Segmental demyelination and remyelination clustered on individual fibres, and g ratios (axon diameter: total fibre diameter) in the sural nerve showed an increased scatter in some cases. Evidence of regeneration was inconspicuous. Unmyelinated fibres were well preserved throughout all the nerves examined. Neurons in the Onufrowicz nuclei, in the intermediolateral columns and in Clarke's columns of the spinal cord were generally well preserved. These observations indicate that a lower motor and primary sensory neuronopathy is a major neurological manifestation in this disease. PMID- 2917279 TI - The Bereitschaftspotential is abnormal in Parkinson's disease. AB - The average Bereitschaftspotential (BP) preceding a rapid, self-paced voluntary extension movement of the index finger was recorded from 6 scalp locations in 14 patients with Parkinson's disease who had been withdrawn from their normal drug therapy for at least 12 h before testing. The amplitude of the potential was measured at the peak negativity (N1) and 650 ms prior to this (NS1), and compared with that recorded in a group of 12 age-matched control subjects. The N1 amplitude was the same as in the normals, but the NS1 component was smaller in the patients, especially in midline leads. As a result, the rise in the BP between the peak NS1 and N1 component (termed NS2) was larger in the patient group. The NS1 component of the BP is thought to reflect preparatory activity in the supplementary motor area (SMA) of cortex. Since the basal ganglia provide a major source of afferent input to SMA, the reduction in NS1 in the patients probably results from inadequate basal ganglia activation of SMA. The larger NS2 component may reflect extra activity in other brain areas to compensate for the reduced SMA activity. PMID- 2917280 TI - Reading with one hemisphere. AB - The subjects of this study were 2 originally right-handed teen-aged girls who had undergone complete hemispherectomy (1 left, 1 right) for intractable epilepsy. Both subjects had developed normal language and reading capacities before the onset of their illness. The reading performance of H.P. (whose right hemisphere had been removed), while not as advanced in level as that of a normal 17-yr-old, showed no abnormality in any subcomponent of reading skill. The reading performance of N.I. (whose left hemisphere had been removed) was poor, but with a pattern of retained and impaired subskills strikingly similar to adult deep dyslexic patients and to split-brain patients given reading tasks lateralized to the left visual field (right hemisphere). The results are discussed with regard to implications for the reading capacity of the nondominant right hemisphere and also its putative contribution to normal reading. PMID- 2917282 TI - Bilingualism and neurolinguistics. PMID- 2917283 TI - Visual field asymmetries in numerical size comparisons of digits, words, and signs. AB - Visual field asymmetries were examined in American Sign Language-English bilinguals for speeded numerical size judgments of pairs of digits, number words, and number signs. Physical size of the number pairs was either congruent or incongruent with their numerical size. The results revealed a greater left visual field (LVF) interference for numbers represented as digits and a greater right visual field (RVF) interference for numbers represented as words or signs. Subjects' performance on number words and signs was also influenced by their skill in English and ASL: interference was greater in the RVF in the subjects' better language but was greater in the LVF for the less skilled language. These findings suggest that lateralization of numerical size judgments is moderated by the mode of number presentation and by prior language experience. PMID- 2917281 TI - Abnormal spatial patterns of elbow muscle activation in hemiparetic human subjects. AB - The patterns of electromyographic (EMG) activity in spastic-paretic and contralateral elbow muscles of 10 hemiparetic human subjects were compared during a sequence of graded voluntary isometric contractions against 4 different-sized loads. These loads were orientated successively at 8 different angles over a 360 degree range, referenced to a plane at the wrist orthogonal to the long axis of the forearm. Comparisons of EMG activity recorded from normal and paretic limbs revealed that there were marked differences in the torque angles which evoked significant EMG activity, in the angular range of EMG, in the angle of peak EMG, and in the scaling of EMG magnitude with increasing isometric loads. In severely impaired limbs, there was a marked shift in both the peak EMG angle and the angular domain of EMG activity for both biceps and triceps muscle groups, away from the normal elbow flexion-extension axis towards external humeral rotation and shoulder girdle elevation. The extent of the disturbance in the spatial patterns of EMG activity was closely correlated with the clinical severity of the spastic-paretic disability, which was quantified using a functional scale patterned after that described by Fugl Meyer et al. (1975). The observed patterns of EMG activity in paretic flexor muscles do not conform with established synergistic patterns, such as might be released by excitation of the flexor reflex in a normal limb. Possible origins for the anomalous EMG patterns are discussed. PMID- 2917284 TI - Language laterality in Navajo reservation children: dichotic test results depend on the language context of the testing. AB - Language lateralization in 40 Navajo and 20 Anglo fifth graders was assessed via the Dichotic Consonant-Vowel Task (DCVT). One group of Navajo children was tested by an experimenter who spoke only Navajo with them. The other Navajo group and the Anglo group were tested by an experimenter who spoke only English to them. Strong right ear advantages (REAs) were obtained for the Anglo group and for the Navajo group tested by the Navajo-speaking experimenter. The Navajo group tested by the English-speaking experimenter showed minimal, nonsignificant REAs. Previous findings of an absence of REAs in Native American children failed to consider the possibility that this might occur only when the experimenter does not speak the dominant language of the children. Our results are not consistent with the view that Native Americans are more right hemisphere dominant as a function of an "appositional" mode of language and thought. PMID- 2917286 TI - Caring for out-of-province patients. PMID- 2917285 TI - Selective crossed aphasia in a trilingual aphasic patient followed by reciprocal antagonism. AB - After surgical removal of a parasitic cyst in the right prerolandic area, an educated 25-year-old male exhibited obvious deficits in one of his three languages (Gujarati), with no measurable deficits in the other two (French and Malagasy). The patient spoke all three languages fluently before the operation. Gujarati and Malagasy had been acquired in infancy. Gujarati was the language of his parents and relatives. Malagasy the language of the local population. All the patient's schooling had been in French, the only language in which he was literate. He used French daily at work. Since the acquisition history for Gujarati and Malagasy was identical, while French had been acquired in a different context, one would have predicted, on the basis of W. Lambert and S. Fillenbaum's (1959, Canadian Journal of Psychology, 13, 28-34) hypothesis, that Gujarati and Malagasy should have been equally affected, with French possibly differently so. However, 8 months postoperatively, the patient had regained control of Gujarati, while Malagasy had deteriorated considerably, and his French remained unimpaired. Two years later, the patient had recovered full use of his three languages. PMID- 2917287 TI - Hyperactivity in children. PMID- 2917288 TI - BScMed program: do finances influence enrollment? PMID- 2917289 TI - The use of vitamin K in the perinatal period. PMID- 2917290 TI - Preventing polydipsia in psychiatric patients. PMID- 2917291 TI - Splenic spite and flawless flight. PMID- 2917292 TI - Licensure: competence to do what? PMID- 2917293 TI - Pertussis vaccine: why do some parents say no? PMID- 2917294 TI - Political awareness of psychiatric patients. PMID- 2917295 TI - There are fewer doctors sitting in new Parliament [correction]. PMID- 2917296 TI - Management of sexually transmitted diseases in Canada, 1989. PMID- 2917297 TI - Occupational exposure to the human immunodeficiency virus among health care workers in Canada. PMID- 2917298 TI - Chronic cough and gastroesophageal reflux. AB - We reviewed the charts of 20 patients with chronic cough of unknown cause who had been referred to a tertiary care respiratory centre from 1980 to 1984 to determine whether gastroesophageal reflux (GER) was a contributing factor. Fifteen of the patients complained of symptoms suggestive of GER: radiologic investigation of the upper gastrointestinal tract revealed hiatus hernia and GER in four, hiatus hernia alone in three, GER alone in two, decreased esophageal peristalsis in one and normal findings in four. Fibreoptic bronchoscopy in the four former smokers and one nonsmoker showed diffuse mucosal erythema. A chest x ray film in one patient showed an infiltrate at the base of the right lung; transbronchial biopsy revealed vegetable material, which confirmed pulmonary aspiration. A 3-month course of medical antireflux treatment (dietary and lifestyle changes, elevation of the head of the bed and administration of cimetidine, antacid and metoclopramide) relieved the chronic cough in 14 of the 20 patients. Of the remaining patients one was lost to follow-up and five had GER confirmed by means of esophagoscopy, esophageal motility testing and long-term intraesophageal pH monitoring; four of the five patients underwent fundoplication and were asymptomatic 3 months after surgery. Antireflux therapy should be considered in patients with chronic cough when other causes have been ruled out, even if there are no GER symptoms. If the treatment fails, full investigation for GER is recommended; if GER is confirmed, surgery should be considered. PMID- 2917299 TI - Insulin-dependent diabetes mellitus in an Inuit child. PMID- 2917300 TI - Contamination of multiple-dose vials due to repeat use of syringes. PMID- 2917301 TI - Let me make myself perfectly obscure. PMID- 2917302 TI - New Royal College council expected to advise local ethics boards. PMID- 2917303 TI - There's no room for freebies in medical journalism. PMID- 2917304 TI - CMA needling leads to changes in federal drug-devices bill. PMID- 2917305 TI - Make it too costly for people to smoke, finance minister advised. PMID- 2917306 TI - As competition increases, so should MD's marketing efforts. PMID- 2917307 TI - High-dose cytosine arabinoside and daunorubicin as primary therapy in elderly patients with acute myelogenous leukemia. A phase I-II study of the Southeastern Cancer Study Group. AB - We undertook a phase I-II trial in elderly (age greater than or equal to 60 years) untreated acute myelogenous leukemia (AML) patients using brief, intensive therapy to improve induction rates and overall survival in older AML patients. Twenty-one patients ranging in age from 60 to 81 years (median, 66 years) were treated using either a 4- or 5-day course of high-dose cytosine arabinoside, 3 g/m2 intravenously (IV) every 12 hours; followed by daunorubicin, 45 mg/m2/d IV bolus for 3 consecutive days. Thirteen patients were entered at the first dose level (a 4-day course or eight doses of cytosine arabinoside), whereas eight patients underwent therapy at the second dose level (a 5-day course or ten doses). Patients who achieved a complete remission received a repeat course of high-dose cytosine arabinoside and daunorubicin within 4 weeks of attaining remission. Seven patients had an antecedant history of a myelodysplastic syndrome. Infection was the major complication experienced by this elderly patient group, and included ten episodes of bacteremia or fungemia (four of which were fatal) and five cases of pneumonia (one fatality). Nine of the 21 patients (three of 13 at the first dose level and six of eight at the second dose level) achieved a complete remission. Median remission duration was 9 months (range, 4 19+ months). Although high-dose cytosine arabinoside plus daunorubicin was an effective antileukemic therapy, it is too toxic to recommend for most elderly leukemic patients. PMID- 2917308 TI - Chlorambucil, vinblastine, procarbazine, and prednisone. An effective but less toxic regimen than MOPP for advanced-stage Hodgkin's disease. AB - The toxicity of MOPP chemotherapy, including nausea, vomiting, hair loss, and neuropathy, can limit patient compliance. Alternative regimens employing oral alkylating agents and vinblastine have been designed to ameliorate these toxicities. The authors reviewed their experience in 24 patients with advanced stage Hodgkin's disease who were treated with chlorambucil, vinblastine, procarbazine, and prednisone (ChlVPP). Complete responses were obtained in 92% (11/12) of previously untreated patients and in 92% (11/12) of patients who relapsed after radiation (10/10) or chemotherapy (one of two). Overall, relapse free survival is 82% with a median duration of follow-up of 5.5 years. Toxicity was minimal with myelosuppression being the dose-limiting toxicity. Severe nausea and vomiting occurred in only two patients and was considered secondary to procarbazine. Mild nausea occurred in six other patients. Minimal alopecia was seen in three patients and only two patients developed a mild peripheral neuropathy. The authors conclude that ChlVPP appears as effective as MOPP chemotherapy for Hodgkin's disease in comparable presentations but is a less toxic regimen. Thus, it may be useful in situations where poor compliance and patient acceptance may compromise optimal dose and frequency of drug administration. PMID- 2917309 TI - Cisplatin and 5-fluorouracil infusion for metastatic colorectal carcinoma. Differences in survival in two patient groups with similar response rates. AB - Because of reported synergism between 5-fluorouracil (5-FU) and cisplatin (CDDP) in L1210 leukemic mice and activity of this combination in clinical studies, a trial was initiated in previously untreated patients with advanced colorectal carcinoma. Cisplatin at 20 mg/m2 and 5-FU as a continuous infusion at 1000 mg/m2 were both administered for 5 consecutive days every 4 weeks. Forty-one patients were treated at Memorial Sloan-Kettering Cancer Center (MSKCC) and 46 were treated by the Community Clinical Oncology Program (CCOP) physicians. A 50% reduction in measurable disease was seen in 12 of 35 (34%) MSKCC patients and in nine of 41 (22%) of the CCOP patients with 95% confidence intervals of 0.18 to 0.50 and 0.10 to 0.35 in the two groups, respectively. The predominant toxicities were as follows: nausea and vomiting, 32%; mucositis, 26%; leukocyte counts less than 2000 cells/mm3, 17%; platelet counts less than 25,000 cells/mm3, 8%; and severe neurotoxicity, 5%. Dose attenuation was similar in the two groups. The median survival was 16.4 months for the MSKCC group and 9.6 months for the CCOP group (P = 0.0003). Although the baseline characteristics (age, sex, performance status, and baseline lactic dehydrogenase [LDH] and alkaline phosphatase) were similar, on further examination differences between the two groups were evident. In the MSKCC group, 14% of patients with liver metastases had greater than 50% of their liver involved with tumor whereas this occurred in 41% of the CCOP group (P = 0.03). The LDH values greater than 500 U/l were observed in 10% of patients in the MSKCC group and in 37% of the patients in the CCOP group (P = 0.007). Characteristics which reflect the bulk of disease, such as the percent of liver involvement, need to be analyzed in order to evaluate purported survival differences in randomized and nonrandomized trials of colorectal carcinoma. PMID- 2917310 TI - Adjuvant oral alkylating chemotherapy in patients with stage I epithelial ovarian cancer. AB - From November 1973 to May 1986, 50 patients with Stage I epithelial ovarian cancer were treated at the University of Kentucky Medical Center (Lexington, KY) with oral Alkeran (melphalan) chemotherapy after primary surgery. Twenty-two patients had Grade 1 tumors, 23 patients had Grade 2 tumors, and five patients had Grade 3 tumors. Patients with ovarian tumors of borderline malignancy were excluded from this study. Twenty-eight patients received from six to 11 courses of chemotherapy and 22 patients completed 12 courses of chemotherapy. Chemotherapy was well tolerated and no patient died of chemotherapy-related complications. Thirty-eight patients underwent second-look laparotomy died of disease 41 months after diagnosis and one patient died with no evidence of disease 6 months after treatment. The actuarial survival of the total group of patients was 98% at 2 years and 94% at 5 years. Fewer than 12 months of chemotherapy may be necessary to obtain long-term survival in these patients. PMID- 2917311 TI - Tamoxifen in combination with cytotoxic chemotherapy in advanced epithelial ovarian cancer. A prospective randomized trial. AB - One hundred patients with Stage III and IV epithelial ovarian cancer participated in a prospective randomized study to determine whether the addition of tamoxifen, an estrogen agonist-antagonist, to standard cytotoxic chemotherapy (doxorubicin, cis-diamminedichloroplatinum) would significantly improve survival. Fifty-one patients received the standard cytotoxic chemotherapy and 49 received tamoxifen as well. No significant difference in overall or progression-free survival between these two patient groups was observed. Cytosol steroid receptor determinations were performed on tumor samples from 72 patients. No correlation was evident between therapy and cytosol estrogen and progestin receptor content of the tumors. This study suggests that the strategy of combining an antiproliferative, hormonally active agent with cytotoxic chemotherapy for management of advanced ovarian cancer may be inappropriate. PMID- 2917312 TI - Activity of pirarubicin (4'-0-tetrahydropyranyladriamycin) in malignant mesothelioma. AB - Eight patients with diffuse malignant mesothelioma of the pleura or peritoneum, previously untreated with chemotherapy, were treated with a new anthracycline 4' 0-tetrahydropyranyladriamycin (pirarubicin). Pirarubicin was given intravenously at the rate of 5 mg per minute, at doses ranging from 35 to 70 mg/m2 once every 21 days. On clinical evaluation, one patient had complete response lasting 4 months. On second-look laparotomy residual tumor was found and she was labelled a partial responder and changed to alternate chemotherapy. Another patient had a partial response of recurrent chest wall tumors lasting 11 months. A third patient had a partial response lasting 4+ months of a pleural-based tumor and resolution of pleural effusion. After the fifth course of chemotherapy, he developed severe granulocytopenia, pseudomonas sepsis, shock, and renal failure. Despite recovery of blood counts to normal within 3 days, renal failure proved fatal. Autopsy revealed only fibrosis and no gross or microscopic evidence of malignant mesothelioma. A fourth patient had improvement in evaluable disease lasting about 4 months; and the remaining four had stable disease for at least 2 months each. The authors conclude that, whenever feasible, noninvasive clinical assessment of tumor response should be supplemented by surgical-pathologic evaluation. Pirarubicin is active in malignant mesothelioma. This is the first report documenting complete tumor eradication after chemotherapy in an adult with malignant mesothelioma. PMID- 2917313 TI - Functional morbidity after regional isolated perfusion of the limb for melanoma. AB - A series of 57 patients still in follow-up after regional isolated perfusion (RIP) of Stage I-II high-risk melanoma is described. Functional morbidity of the perfused limb was investigated. Median interval after RIP was 5 years. With no regard to recurrent disease subjectively only one patient had severe complaints of the perfused limb. Objective investigation showed no edema or atrophy in 80% of the upper limbs and in 64% of the lower limbs. Concerning the mobility of the joints in the upper limb we found in four cases a disturbed function in several movements. More restriction were observed in the lower leg. Especially the ankle showed severe functional restrictions in more than 25%. PMID- 2917314 TI - Primary central nervous system lymphoma in AIDS. Results of radiation therapy. AB - Primary central nervous system (CNS) lymphoma is one of the clinical presentations of the acquired immune deficiency syndrome (AIDS). Ten patients had biopsy-proven high-grade lymphomas that were confirmed by further staging as limited to the CNS. All ten patients received cranial irradiation (total dose, 2200 to 5000 cGy). Six patients demonstrated complete response (CR) of the intracranial masses at the time of repeat computed tomography (CT) scan, whereas one attained a partial response (PR). Two of the CR patients died of multiple opportunistic infections, two experienced relapse of lymphoma, and died at 7 and 16 months from diagnosis, and two were alive without evidence of disease at 8 and 14 months from diagnosis. The median survival of the whole group was 5.5 months (range, 2 to 16 months). Patients with AIDS-related primary CNS lymphoma may respond to radiation treatment; however, response duration is usually short, and survival is influenced by refractory disease or systemic opportunistic infections. PMID- 2917315 TI - Comparison of abdominopelvic computed tomography results and findings at second look laparotomy in ovarian carcinoma patients. AB - In 35 women with epithelial carcinoma of the ovary, the results of restaging laparotomy were compared with the preoperative abdominopelvic computed tomography (CT) findings to evaluate the accuracy of CT for determining tumor status. In the 36 studies performed, enhanced CT scans at 10-mm to 15-mm intervals had a sensitivity of 84% and a specificity of 88%; in addition, there was 86% agreement between the CT and surgical findings. These results suggest that although CT is not accurate enough to completely replace the restaging laparotomy, its high accuracy in determining residual disease after treatment is helpful for patient management. PMID- 2917316 TI - Genetic variation of haptoglobin and transferrin in relation to DNA content and stage in renal cell carcinoma. AB - Four genetic marker systems were investigated in 102 patients with renal cell carcinoma. The previously observed excess of the transferrin (TF) variant C3 among male patients was confirmed. Interestingly, an excess of TFC3 and a deficit of the haptoglobin heterozygote, HP2-1, were associated with diploid tumor DNA content and Stage I, particularly in male patients. The results are discussed in terms of a possible genetic influence on tumor progression. PMID- 2917317 TI - Grades of nodular sclerosis (NSI-NSII) in Hodgkin's disease. Are they of independent prognostic value? AB - Subclassification of the nodular sclerosis (NS) type of Hodgkin's disease in Grade 1 and 2 was reported for the first time by the British National Lymphoma Investigation (BNLI). Three groups, the BNLI, Gartner et al. and the current authors, found clearly different survival rates between Grade 1 and 2 NS patients. The authors studied retrospectively if this NS grading has an independent prognostic value in 90 NS patients, diagnosed in ten hospitals in the southeastern part of the Netherlands (1972-1983). In this study there is no significant difference in sex, age, B-symptoms, erythrocyte sedimentation rate (ESR), stage, positive laparotomy, involvement of mediastinum or spleen, lymphocyte count, and percentage of complete remissions between the NS subgroups. Multivariate analysis suggests that the subclassification of NS in Grades 1 and 2 is a prognostic factor in survival independent of age, stage and ESR. This finding and the high relative frequency of NS makes application of this NS subdivision probably clinically useful to identify patients for a risk-adapted therapy. PMID- 2917318 TI - Pseudoangiomatous hyperplasia of mammary stroma. Some observations regarding its clinicopathologic spectrum. AB - Pseudoangiomatous hyperplasia of mammary stroma (PHMS) is a benign proliferation of keloid-like fibrosis, containing slit-like pseudovascular spaces. Its main importance is its distinction from angiosarcoma; however, the clinicopathologic spectrum of PHMS remains incompletely described. We report two new cases and describe our findings in 200 consecutive breast specimens evaluated for the presence of PHMS. The first patient presented with peau-de-orange change in the overlying breast skin, thus mimicking inflammatory breast carcinoma. Furthermore, this patient's PHMS lesion had been diagnosed and treated inappropriately as a low-grade angiosarcoma. The second case showed the more typical, fibroadenoma like presentation of PHMS. In addition, PHMS changes occur commonly in routine breast biopsy specimens. In fact, our review of 200 consecutive breast specimens showed PHMS in at least one microscopic focus in 23% of cases. The PHMS changes occurred in younger patients than the control population and were associated with fibrocystic changes, in fibroadenomas, in gynecomastia, in normal breast tissue, and in sclerosing lobular hyperplasia. Ultrastructural and immunohistochemical studies of one case showed that the capillary-like spaces were either acellular or lined by fibroblasts. Pseudoangiomatous hyperplasia of mammary stroma represents a clinicopathologic spectrum, extending from focal, insignificant microscopic changes to cases where PHMS produces a breast mass. Increased awareness of PHMS and its clinicopathologic spectrum will allow its differentiation from other vascular tumors of the breast, especially low-grade angiosarcoma. PMID- 2917319 TI - DNA flow cytometry as a predictor of outcome of stage I renal cell carcinoma. AB - The features most frequently used in predicting the outcome of renal cell carcinoma are stage at presentation and nuclear grade. Recently DNA ploidy pattern, as detected by DNA flow cytometry has also been shown to be predictive. In this study DNA flow cytometry was performed on formalin-fixed paraffin embedded tissue from 50 patients with Stage I renal cell carcinoma for whom long term follow-up data were available. Two were eliminated for technical reasons. Of the 48 evaluable tumors, 25 (52%) were diploid, 19 (40%) were nondiploid, and in four, (8%) the ploidy was uncertain. The ploidy pattern was statistically significantly associated with nuclear grade (P less than 0.02), and primary tumor size (P less than 0.05) but did not correlate with cell type, microscopic growth pattern, or the presence or absence of mitotic activity. In the group as a whole, ten patients (21%) died of renal cell carcinoma, seven of 19 (37%) with nondiploid tumor patterns, and two of 25 (8%) with a diploid pattern (P less than 0.03). One of four patients (25%) with tumors of uncertain ploidy also died. However, only two factors, nuclear grade and primary tumor size, were independent predictors of outcome. For Stage I renal cell carcinoma, ploidy can significantly predict patient outcome and correlates with nuclear grade and tumor size, but is not an independent predictive variable. PMID- 2917320 TI - Gangliosides of human melanoma. AB - Human melanoma synthesizes a large quantity of gangliosides, glycosphingolipids containing sialic acid. The authors previously have demonstrated that the ganglioside profile differs among individual melanomas and is widely heterogeneous. In the current study, a retrospective study was performed to compare the relationship between the quantity of five major gangliosides of human melanoma (GM3, GM2, GD3, GD2, and alkali-labile ganglioside) and nine clinical factors (sex, age, site, stage, tumor size, pigmentation, histopathologic type of primary tumor, chemosensitivity, and prognosis). Melanoma specimens studied were obtained from patients of our clinic and included 52 biopsy specimens and 28 cultured cell lines. Analysis of melanoma biopsy specimens have shown a differential ganglioside expression among different sites of tumor, pigmentation, and histopathologic types. Results of cultured melanoma cell lines differed from those of biopsy specimens, but ganglioside expression also differed among the site of tumor, tumor size, histopathologic types, and chemosensitivity. GM3 positively correlated with a good prognosis in both biopsy and cultured melanomas. PMID- 2917321 TI - Oxyphil and squamous variants of medullary thyroid carcinoma. AB - Two unusual morphologic variants of medullary thyroid carcinoma not previously described are reported. The first tumor was composed predominantly of large eosinophilic cells indistinguishable at the light microscopic level from Hurthle cells. Focal areas of conventional medullary carcinoma were also present. Electron microscopic study showed mitochondrion-rich cells containing round neurosecretory granules. Immunoreactive calcitonin and carcinoembryonic antigen (CEA) were demonstrated within most tumor cells. The second tumor had areas of typical medullary carcinoma but exhibited extensive squamous differentiation. The tumor was positive for CEA, neuron-specific enolase, and chromogranin but negative for calcitonin. Oxyphil and squamous cells must be added to the long list of cell types that have been described in medullary thyroid carcinoma. PMID- 2917322 TI - Clinical manifestations of ganglioneuroma. AB - Ganglioneuroma may occur spontaneously or after therapy for neuroblastoma. This lesion may be metastatic or unresectable in the primary site. The rarity of this situation and lack of understanding of the biology of this benign condition may lead to extensive, potentially life-threatening attempts at surgical resection or the futile use of chemotherapy or radiotherapy to try to cause regression or control growth. The authors present here several cases which demonstrate the multiple presentations of ganglioneuroma and the potential problems which may arise in their management. PMID- 2917323 TI - Synchronous tumors arising in a single major salivary gland. AB - Multiple separate tumors arising in the major salivary glands are distinctly unusual. The records on 25 patients with synchronous unilateral salivary gland tumors on file at St Louis University and at the Armed literature. Bilateral tumors arose more frequently than multiple unilateral ones. The most common tumors with bilateral synchronous or metachronous development are the Warthin tumors, with more than 100 reported cases; the mixed tumor with at least 34 cases; and the acinic cell carcinoma, with 12 reported cases. The Warthin tumor also was the most likely to present with multifocal unilateral involvement with 29 tumors having three or more separate foci of tumor. The next most common tumor combinations are a Warthin tumor and a mixed tumor (20 cases), the multifocal membranous basal cell adenoma (12 cases), and multiple oncocytomas (nine cases). Numerous other tumor combinations were found covering the range of salivary gland neoplasia, however one of the tumors usually was a mixed tumor or a Warthin tumor. PMID- 2917324 TI - Right ventricular metastatic melanoma 27 years after resection of the primary tumor. AB - This article is a case report of a 65-year-old white woman with a history of malignant melanoma, resected from her back in 1959. She presented 27 years later with right-sided heart failure and metastatic melanoma to her right ventricle. To the authors' knowledge, a large ventricular mass as the sole site of disease recurrence has not been described previously. PMID- 2917325 TI - Dysplastic naevi in a population-based survey. AB - The prevalence of dysplastic naevi was studied in a population-based survey of 380 30 to 39-year-old and 50 to 59-year-old non-Maoris in Milton, a small town in the south of New Zealand. Photographs of all pigmented naevi greater than or equal to 4 mm in diameter were taken during the survey and subsequently evaluated by two experienced reviewers. Nine percent of the group (95% CI, 6%-13%) were judged to have one or more dysplastic naevi. Interobserver agreement over the diagnosis of dysplastic naevi was 85% (kappa = 0.55). Dysplastic naevi were associated with higher counts of moles greater than or equal to 2 mm in diameter; 50 or more such moles increased the likelihood of having three or more dysplastic naevi about 40-fold. Naevi judged to be dysplastic were, therefore, relatively common and were associated with increased numbers of common moles. PMID- 2917326 TI - Der(5)t(5;7)(q11.2;p11.2): a new recurring abnormality in malignant myeloid disorders. AB - Complete or partial monosomy for the long arm of chromosomes 5 and/or 7 is frequently observed in malignant cells from patients with a therapy-related myelodysplastic syndrome (t-MDS) or therapy-related acute nonlymphocytic leukemia (t-ANLL). Partial monosomy is usually the result of a chromosomal deletion; however, unbalanced translocations have also been observed. We have identified one such translocation in three patients who had either t-ANLL or a primary MDS. The genetic consequences of this translocation [-5,-7,+der(5)t(5;7)(q11.2;p11.2)] are partial monosomy for the long arm of chromosome 5 and complete monosomy for the long arm of chromosome 7. Thus, this rearrangement may represent a new, recurring abnormality that is associated with malignant myeloid disorders. PMID- 2917327 TI - Translocation t(8;16)(p11;p13) in acute nonlymphoblastic leukemia (M4) possibly secondary to Hodgkin's disease. AB - Simultaneous involvement of bands 8p11 and 16p13 in a primary, even though rare, chromosomal translocation recently described in acute nonlymphocytic leukemia may be of crucial interest in some subtypes of this acute leukemia, particularly in the monocytic form. In the present report we describe this translocation in acute nonlymphoblastic leukemia FAB M4, possibly secondary to Hodgkin's disease, though it is also possible that the leukemia may have developed de novo. The aberration t(8;16)(p11;p13) was present in 100% of direct and cultured bone marrow cell preparations. A very high frequency of cells with nonclonal structural chromosome aberrations was also observed in peripheral blood cultures (more than 53%). Random translocations and deletions constituted most of the observed alterations. These findings are discussed with regard to the relationships between secondary leukemias and intensive polychemotherapeutic treatments of primary neoplasias. PMID- 2917328 TI - Simultaneous existence of double minute chromosomes and a homogeneously staining region in a retinoblastoma cell line (Y79) and amplification of N-myc at HSR. AB - We observed double minute chromosomes (dmin) and a homogeneously staining region (HSR) in the same metaphase cells obtained from a retinoblastoma cell line, Y79. All of the 132 metaphases examined contained an HSR on the short arm of chromosome 1(1pHSR) and five cells (3.8%) had two to four dmin. To determine whether 1pHSR and dmin carried amplified N-myc sequences, we performed an in situ hybridization using an N-myc probe. Silver grains clustered on and along the 1pHSR, but not on the dmin. These findings indicate that the HSR on chromosome 1 is associated with amplification of N-myc in Y79 cells. PMID- 2917329 TI - Separate karyotypic features in a local recurrence and a metastasis of a fibrosarcoma. PMID- 2917330 TI - ins(6;1) in a patient with congenital leukemia. AB - Q- and C-banded karyotypes of leukemic cells of a patient with congenital acute lymphoblastic leukemia showed the karyotype: 46,XX,ins(6;1)(p21;p13p36). This rearrangement is unusual, and the breakpoints on chromosome 1 are interestingly close to known cellular oncogenes (N-ras, fgr, src-2) and to a putative antioncogene. PMID- 2917331 TI - Cytogenetic analysis of different cellular populations in chronic myelomonocytic leukemia. AB - Karyotypes of different cellular populations made after separation of bone marrow cells on a gradient of Percoll were evaluated in seven patients affected by chronic myelomonocytic leukemia diagnosed according to FAB criteria. Megakaryocytes, monocytic cells, and granulocytic and erythroid precursors were preferentially collected after centrifugation between density layers of 1045-1050 mg/ml, 1050-1060 mg/ml, and 1065-1070 mg/ml, respectively. The enriched cell fractions were cultured separately and submitted to cytogenetic investigation after short-term culture. Some chromosome aberrations (5q-,+8) were observed in all cellular fractions in three patients, thus providing cytogenetic evidence of the involvement of a common progenitor stem cell in this myelodysplastic disorder. On the other hand, chromosome abnormalities such as del(3)(q21) and del(11)(q23) appeared to be confined to the megakaryocytic and the monocytic fractions, respectively, in two patients. It is conceivable that lineage restricted aberrations may develop as a consequence of a multistep clonal evolution and may show a close relationship with the hemopoietic differentiative processes. PMID- 2917332 TI - Uterine leiomyoma cytogenetics. I. Rearrangements of chromosome 12. AB - Cytogenetic investigation on 19 benign tumors of uterine smooth muscle was carried out after short-term cultures. Clonal chromosome abnormalities were present in four cases; 15 had normal karyotypes. All four cases with abnormal karyotype showed changes of chromosome 12. In three cases, chromosome 12 was involved in structural rearrangements with chromosome X, 1, and 4, respectively. Breakpoints on this chromosome occurred in different regions. The fourth case had trisomy 12 and an extra deleted chromosome 2, del(2)(p22). These findings confirm the involvement of chromosome 12 in uterine leiomyoma. PMID- 2917333 TI - Cytogenetic abnormalities in an angioleiomyoma. AB - We have cytogenetically investigated short-term cultures from an angioleiomyoma. Monosomy for chromosome 13, and one to two small markers were observed in the tumor cells, resulting in the karyotype 46-47,XY,-13,+1-2 mar. PMID- 2917334 TI - The chemotherapeutic drug melphalan induces breakage of chromosomes regions rearranged in secondary leukemia. AB - A cytogenetic study is reported on the lesions induced in vitro by melphalan, a currently used anticancer drug. The distribution of 2166 breakpoints shows that they do not occur at random. There is a large excess of breaks in region q1 of chromosome 9 and R bands are significantly more affected than G-band-rich segments. Furthermore, some regions of chromosomes 5, 7, 11, and 17, which are the chromosomes usually rearranged and deleted in secondary leukemias, presumably induced by such treatments, are frequently affected. It is presumed that the frequent involvement of 9q1 largely reflects preexisting monostrand breaks. The frequent breakage of chromosomes 5, 7, 11, and 17 and of R bands in general, which are known to be G-C rich, may result from the preferential methylation of the O6 of guanine by melphalan. PMID- 2917335 TI - Nonrandom chromosomal aberrations are associated with sites of tissue involvement in non-Hodgkin's lymphoma. AB - In an effort to assess the utility of pretreatment cytogenetics as indicators of sites of involvement by lymphoma, clinical and cytogenetic correlations were performed on 133 consecutive specimens derived from 130 patients with non Hodgkin's lymphoma. Nonrandom chromosomal aberrations detected at the time of diagnosis were associated with sites of clinical involvement presenting initially or during the progression of the lymphoma. Statistically significant associations included translocation breaks involving the chromosomal region 1p32-36 and bone marrow involvement, chromosome 14 abnormalities including breaks at 14q22-24 and splenic involvement, chromosome 9 abnormalities and pulmonary involvement, and monosomy 11 and bone involvement. A significant correlation was also observed between breaks involving the region 6q22-24, detected during the course of disease, and bone marrow involvement by lymphoma. The relationship of the sites of nonrandom chromosomal breakage reported here to known cellular oncogenes and implications to concepts of tumor evolution and spread are discussed. PMID- 2917336 TI - Translocation t(1;19)(q23;p13) in acute lymphoblastic leukemia. A report on six new cases and an unusual t(17;19)(q11;q13), with special reference to prognostic factors. AB - We report clinical, immunologic, and cytogenetic characteristics of six patients with a t(1;19)(q23;p13) that was balanced in one case and of the unbalanced type [-19,der(19)t(1;19)(q23;p13)] in the remaining five cases. Intracytoplasmic immunoglobulins (cIg) were positive in the three cases where they were found. We also report on another patient, with a t(17;19) involving 17q11 and probably 19q13 regions, although involvement of 19p13 could not be excluded. In this patient, cIg were also present, thus raising the issue of whether such a rearrangement could be a variant of t(1;19). Clinically, five patients belonged to the high-risk acute lymphoblastic leukemia (ALL) group, because of high leukocytosis, central nervous system (CNS) disease at presentation, or massive organomegaly. Cytologically, all cases were FAB type L1. Except for the two cases allografted in the first complete remission (CR) all patients relapsed, three of them within 13 months. Two CNS relapses were seen in spite of adequate CNS prophylaxis. ALL with t(1;19) appears to be a poor-risk ALL subgroup and probably requires a reinforcement of therapeutic modalities that might include, when possible, allografting at first CR. PMID- 2917337 TI - Mechanism of i(6p) formation in retinoblastoma tumor cells. AB - Isochromosome (6p) represents a highly characteristic cytogenetic abnormality of human retinoblastoma (RB) cells and may be important for tumor progression. To elucidate the mechanism by which this abnormal chromosome is formed, 24 RB tumors and three cell lines were studied by means of DNA polymorphisms specific for the short arm and the long arm of chromosome 6. Our results indicate that mitotic nondisjunction leading to trisomy 6 precedes the isochromosome formation. The isochromosome may then be formed by transverse division of the centromere or intrachromosomal chromatid exchange. PMID- 2917338 TI - Tetra-n-propylporphycene as a tumour localizer: pharmacokinetic and phototherapeutic studies in mice. AB - The porphin isomer tetra-n-propyl-porphycene (TPP) was incorporated into unilamellar liposomes of dipalmitoylphosphatidylcholine and intravenously injected at a dose of 2 mg/kg to BALB/c mice bearing a MS-2 fibrosarcoma. Pharmacokinetic studies show that TPP is selectively transported by serum lipoproteins and delivered to the tumour tissue with good efficiency (approx. 1 microgram of the TPP per g of tissue at 24 h after injection) and selectivity (ratio of TPP concentration in the tumour to the peritumoural tissue 16.7 at 24 h). Large doses of TPP are also accumulated by the liver, in agreement with the elimination of the drug via the biliary route, while no TPP is recovered from the brain. Red light-irradiation (300 J/cm2) of the tumour area caused extensive necrosis, while only little cutaneous photosensitivity was observed. Since TPP has a large absorbance in the 630-640 nm region, can be synthesized with a high degree of purity and is an efficient generator of singlet oxygen, this drug represents a potential candidate as a phototherapeutic agent for tumours. PMID- 2917339 TI - Altered methionine metabolism in metastatic variants of a human melanoma cell line. AB - In order to identify the biochemical defect(s) responsible for the reduced levels of DNA 5-methylcytosine (5-mCyt) found within highly metastatic (in athymic "nude" mice) variants of the poorly metastatic human melanoma cell line MeWo, the ability of these cells to grow in culture medium devoid of exogenous methionine but containing either homocysteine (Hcy) or 5'-deoxy-5'-methylthioadenosine (MeSAdo) was determined. In contrast to the parental MeWo tumor line, many (but not all) of these malignant variants were completely unable to proliferate in methionine-free homocysteine-containing medium. Many of these malignant variants also exhibited a reduced ability to proliferate in methionine-free MeSAdo containing medium. Cell lines established from "artificial" metastases of MeWo or its cloned sublines, exhibited no consistent reduction in their ability to grow in methionine-free medium containing either Hcy or MeSAdo. These observations suggest that alterations in S-adenosylmethionine(AdoMet)-dependent transmethylation reactions may contribute to "progression" of the MeWo tumor from a relatively benign to a highly autonomous and malignant state. PMID- 2917340 TI - Stabilization and quantitative analysis of fecapentaenes in human feces, using synthetic fecapentaene-12. AB - Naturally occurring fecal mutagens, called fecapentaenes, are hypothesized to contribute to large bowel carcinogenesis. To understand health risks it is necessary to relate fecal mutagen concentrations to intestinal pathologies, i.e. colon cancer. However, fast and reliable methods for analysis of stool for fecapentaene levels are not available. This study presents an evaluation of stabilizing effects on synthetic fecapentaene-12 of various antioxidants, indicating tri-ethylamine to give the best results. Furthermore, it describes a fast extraction procedure for human stool and a subsequent HPLC-analysis which produces quantitative data on fecapentaene-12 concentrations within 30 min. PMID- 2917341 TI - Dietary ellagic acid reduces the esophageal microsomal metabolism of methylbenzylnitrosamine. AB - Dietary ellagic acid has been shown to reduce the incidence of methylbenzylnitrosamine-induced esophageal carcinoma in the rat. Methylbenzylnitrosamine (MBN) is a naturally occurring carcinogen which requires cytochrome P-450 dependent activation to be mutagenic. We examined whether the reduction in tumor incidence observed with dietary ellagic acid was associated with alterations in the cytochrome P-450 dependent microsomal metabolism of MBN. Dietary ellagic acid was shown to significantly reduce total esophageal and hepatic microsomal cytochrome P-450 (P less than 0.05) and significantly reduce the esophageal microsomal metabolism of MBN (P less than 0.05). The addition of ellagic acid in vitro also resulted in a significant inhibition (P less than 0.05) of the esophageal microsomal metabolism of MBN. In contrast, dietary ellagic acid and the addition of ellagic acid in vitro did not alter the hepatic microsomal metabolism of MBN. The reduced rate of MBN metabolism by the esophageal microsomes from the ellagic acid fed rats may contribute to the decreased incidence of esophageal carcinoma observed in these animals. PMID- 2917342 TI - The effect of breast tumour and normal breast tissue cytosols on oestradiol 17 beta-hydroxysteroid dehydrogenase activity. AB - We have prepared cytosols of normal breast tissue and breast tumour tissue and examined their effect on 17 beta-oestradiol dehydrogenase (E2DH) activity in cultured normal breast fibroblasts and on the MCF-7 breast cancer cell line. Tumour cytosol increased the activity of E2DH in the reductive (E1----E2) direction in both MCF-7 cells and normal breast fibroblasts. E2DH activity in the oxidative (E2----E1) direction did not change. Increasing the amount of tumour cytosol progressively raised E2DH activity in the E1----E2 direction in MCF-7 cells, whereas equivalent amounts of cytosol from normal tissue had no effect. No change was seen in the oxidative direction. These findings suggest that a factor present in breast tumours may influence E2DH activity and consequently, the hormonal environment and growth of tumours. PMID- 2917343 TI - Natural killer sensitivity of four Bomirski melanoma variants. AB - The sensitivity of four hamster melanoma variant cells to natural killer (NK) cell lysis mediated by hamster blood and spleen mononuclear cells is examined. The melanoma variants differed in their differentiation level, growth rate, and frequency and localization of metastases. The cells of the melanoma variants were found to differ in their sensitivity to NK cell mediated lysis. A consistent relationship between high sensitivity to lysis and such tumor characteristics as low differentiation level, slow growth rate, low metastatic potential was not observed. PMID- 2917344 TI - Effect of tumour location on selective uptake and retention of phthalocyanines. AB - The effect of anatomical site of tumour growth on selective uptake and retention of chloro-aluminium sulphonated phthalocyanine (ClAlSPc) was determined using the murine colorectal carcinoma (Colo 26). Tumours were established in the liver, spleen, kidney, lung, thoracic cavity and s.c. flank region of syngeneic BALB/c mice and animals received 10 mg/kg ClAlSPc by i.v. injection. Colo 26 growths at s.c., intra-pulmonary, intra-thoracic or intra-renal sites took up and retained greater amounts of ClAlSPc than did adjacent normal tissues. Such selective retention of ClAlSPc by neoplastic tissue was not observed when Colo 26 was grown in the spleen, where tumour and normal tissue took up about the same amounts, or the liver, where normal tissue took up more ClAlSPc than either directly implanted or metastatic tumours. ClAlSPc ratios found in tumour/adjacent tissue may vary for a single tumour growing at different anatomical sites and such variability could have a distinct effect on the efficacy of photodynamic therapy of cancer. PMID- 2917345 TI - Use of primary cultures of human hepatocytes in toxicology studies. AB - Often results from toxicological studies using rodent models cannot be directly extrapolated to probable effects in human beings. In order to examine the genotoxic potential of chemicals in human liver cells, a human hepatocyte DNA repair assay has been defined. Procedures were optimized to prepare primary cultures of human hepatocytes from discarded surgical material. On eight different occasions human hepatocyte cultures of sufficient viability to measure DNA repair were successfully prepared by collagenase perfusion techniques. The cells were allowed to attach to plastic or collagen substrata for periods of 1.5 to 24 h and subsequently incubated with [3H]thymidine and test chemicals for periods of 18 to 24 h. Chemically induced DNA repair, measured as unscheduled DNA synthesis, was quantitated autoradiographically. The following compounds were tested: 2-acetylaminofluorene, aflatoxin B1, 2-aminobenzyl alcohol, aniline, benzo(a)pyrene, carbon tetrachloride, chloroform, 2,4-diaminotoluene, 2,6 diaminotoluene, di(2-ethylhexyl)phthalate, dimethylnitrosamine, 1,6 dinitropyrene, 2,4-dinitrotoluene, 2,6-dinitrotoluene, methyl chloride, 5 methylchrysene, mono(2-ethylhexyl)phthalate, 2-methyl-2-P-(1,2,3,4-tetrahydro-1 naphthyl)phenoxypropionic acid (nafenopin), beta-naphthylamine, nitrobenzene, 2 nitrobenzyl alcohol, 2-nitrotoluene, 2,3,7,8-tetrachlorodibenzo-p-dioxin, unleaded gasoline, and 4-chloro-6-(2,3-xylidino)-2-pyrimidinylthioacetic acid (Wy 14,643). In only one of eight cases did some of the chemicals generally regarded as genotoxic fail to give a positive response. For purposes of comparison, all test chemicals were evaluated in the in vitro rat hepatocyte DNA repair assay. Individual-to-individual variation in the DNA repair response was far greater for the human cultures than for cultures derived from rats. For only three chemicals was there a qualitative difference in the response between the rodent and the human cells; beta-naphthylamine was positive in the rat but in none of the human cultures examined, whereas the opposite was seen for 2,6-diaminotoluene and 5 methylchrysene. Clofibric acid, mono(2-ethylhexyl)phthalate, and Wy-14,643 induced enzymes indicative of peroxisomal proliferation in primary rat hepatocyte cultures, but not in two human hepatocyte cultures. These results indicate that, in general, the in vitro rat hepatocyte DNA repair assay is a valid model for predicting potential genotoxic effects in human beings. However, rodent hepatocytes may not be appropriate for assessing the potential of chemicals to elicit nongenotoxic effects in human beings such as the induction of hepatocyte peroxisomal proliferation. PMID- 2917346 TI - Behavior of activities of thymidine metabolizing enzymes in human leukemia lymphoma cells. AB - The behavior of the activities of thymidine metabolizing enzymes, dihydrothymine dehydrogenase (EC 1.3.1.2) and thymidine phosphorylase (EC 2.4.2.4) for thymidine degradation, thymidine kinase (EC 2.7.1.75) and thymidylate synthase (EC 2.1.1.45) for DNA synthesis, was elucidated in cytosolic extracts from normal human lymphocytes and 13 human leukemia-lymphoma cell lines. In the normal human lymphocytes, the activities of dihydrothymine dehydrogenase, thymidine phosphorylase, thymidine kinase, and thymidylate synthase were 6.88, 796, 0.30, and 0.29 nmol/h/mg protein, respectively. In leukemia-lymphoma cell lines, the activities of synthetic enzymes, thymidine kinase, and thymidylate synthase, increased two- to 79-fold and 22- to 407-fold of the normal lymphocyte values. In contrast, the activities of the catabolic enzymes, dihydrothymine dehydrogenase and thymidine phosphorylase, decreased to 5-42% and 3-38% of the values of normal lymphocytes. As a result, the ratio of activities of thymidine kinase/dihydrothymine dehydrogenase was elevated by 7- to 1170-fold, respectively. Thus, reciprocal behavior in the activities of the opposing enzymes in thymidine metabolism was observed in human leukemia-lymphoma cells. Polyclonal and monoclonal antibodies against dihydrothymine dehydrogenase were prepared and studies on immunotitration of this enzyme with these antibodies showed that the enzyme protein amount in Jurkat leukemic cells was 36% of that of normal lymphocytes. This was in good agreement with the decrease in the activity of the enzyme to 32%, indicating that the decrease in activity in the leukemic cells was due to the decline in the amount of enzyme protein. The metabolic imbalances in thymidine utilization appear to be characteristic of human leukemia-lymphoma cells. These observations should confer selective advantages to the lymphoproliferating cells and mark out the catabolic, as well as the synthetic, enzymes as important targets in the design of chemotherapy. PMID- 2917347 TI - Effect of cancer on the in vivo energy state of rat liver and skeletal muscle. AB - The effect of increasing tumor burden on host liver and skeletal muscle energy status was studied using P-31 nuclear magnetic resonance spectroscopy (NMR), in rats inoculated with a nonmetastasizing methylcholanthrene-induced sarcoma (TB), and compared to nontumor bearing (NTB) and pair-fed (PF) rats. During the 28-day study, serial measurements of body weight, food intake, and tumor volume were obtained. Using a 0.9-cm double-turn surface coil, weekly NMR measurements were obtained from liver and skeletal muscle. An increasing ratio of [Pi]/[ATP] was used as one measure of intracellular energy depletion. [Pi]/[ATP] in NTB rats remained constant over time at 0.78 +/- 0.10 in liver, and 0.30 +/- 0.10 in skeletal muscle. In TB rats, the [Pi]/[ATP] ratio increased significantly in liver (P = 0.00002) and skeletal muscle (P = 0.04) with increasing tumor burden. In PF rats, no significant change occurred in [Pi]/[ATP] in liver or skeletal muscle, indicating that declining food intake was not responsible for the change in [Pi]/[ATP] seen in TB rats. Surface-coil spectroscopy of liver and skeletal muscle permits serial measurement of visceral energy stores. Increasing tumor burden results in early, ongoing depletion of energy stores as reflected by increasing [Pi]/[ATP] in these organs. PMID- 2917348 TI - 32P-postlabeling analysis of DNA adducts in liver of wild English sole (Parophrys vetulus) and winter flounder (Pseudopleuronectes americanus). AB - The 1-butanol adduct enhancement version of the 32P-postlabeling assay was used to measure the levels of hepatic DNA adducts in the marine flatfish, English sole (Parophrys vetulus), sampled from the Duwamish Waterway and Eagle Harbor, Puget Sound, WA, where they are exposed to high concentrations of sediment-associated chemical contaminants and exhibit an elevated prevalence of hepatic neoplasms. Hepatic DNA was also analyzed from English sole from a reference area (Useless Bay, WA) and from reference English sole treated with organic-solvent extracts of sediments from the two contaminated sites. Autoradiograms of thin-layer chromatograms of 32P-labeled hepatic DNA digests from English sole from the contaminated sites exhibited up to three diagonal radioactive zones, which were not present in autoradiograms of thin-layer chromatogram maps of 32P-labeled DNA digests from English sole from the reference site. These diagonal radioactive zones contained several distinct spots as well as what appeared to be multiple overlapping adduct spots. The levels (nmol of adducts/mol of nucleotides) of total DNA adducts for English sole from Duwamish Waterway and Eagle Harbor were 26 +/- 28 (DS) and 17 +/- 9.6, respectively. All autoradiograms of DNA from fish from the contaminated sites exhibited a diagonal radioactive zone where DNA adducts of chrysene, benzo(a)pyrene, and dibenz(a,h)anthracene, formed in vitro using English sole hepatic microsomes, were shown to chromatograph. English sole treated with extracts of the contaminated sediments had adduct profiles generally similar to those for English sole from the respective contaminated sites. The chromatographic characteristics of the adducts and the similarities in adduct profiles between field-sampled English sole and those treated with contaminated sediment extracts suggested that hydrophobic aromatic compounds of anthropogenic origin were adducted to hepatic DNA of sole from contaminated sites, but not in sole from the reference site. Moreover, an initial study with winter flounder (Pseudopleuronectes americanus) from Boston Harbor, MA, an area where high concentrations of sediment-associated chemicals are present, revealed a pattern of hepatic DNA-adducts (9.0 +/- 7.8 nmol of adducts/mol of nucleotides) similar to that observed for English sole from Eagle Harbor. PMID- 2917349 TI - Effects of oral administration of sulfolithocholic acid disodium salt and lithocholic acid sodium salt on N-methyl-N-nitrosourea-induced colonic tumorigenesis in conventional rats. AB - Effects of p.o. administration of sulfolithocholic acid disodium salt (SLCNa) and lithocholic acid sodium salt (LCNa) on N-methyl-N-nitrosourea (MNU)-induced colonic tumorigenesis were studied in conventional rats. Female F344 rats received either 0.5 ml of distilled water (DW) alone or DW containing 2.5 mg of MNU twice in 1 wk intrarectally. Then rats were fed freely on a basal diet (PCE 2) or PCE-2 containing LCNa or SLCNa (both at 0.5 mmol/100 g of PCE-2) for 40 wk. Thus, 6 groups were completed: MNU + PCE-2 (n = 30); MNU + LCNa (n = 29); MNU + SLCNa (n = 22); DW + PCE-2 (n = 17); DW + LCNa (n = 20); and DW + SLCNa (n = 19). Numbers of rats bearing colonic tumor were 3 (10%) in MNU + PCE-2, 2 (7%) in MNU + LCNa, and 8 (36%) in MNU + SLCNa group (uncorrected x2 = 9.35 among the 3 groups), but none in those groups without MNU. Total fecal bile acids in the rats given bile salts showed about 2-fold increase compared with those without bile salts. Fecal bile acid profiles between the LCNa and SLCNa groups were indistinguishable except for a slight increase of sulfolithocholic acid in the SLCNa groups. These results indicated that p.o. administration of SLCNa but not LCNa promoted MNU-induced colonic tumorigenesis in conventional rats. Fecal bile acid profiles did not support the higher tumor incidence in the MNU + SLCNa group compared with the MNU + LCNa group, which suggested that an unrecognized mechanism probably relating to desulfation of SLCNa was involved in this phenomenon. PMID- 2917350 TI - Human and rat kidney cell metabolism of 2-acetylaminofluorene and benzo(a)pyrene. AB - The metabolism and mutagenic activation of the model carcinogens benzo(a)pyrene [B(a)P] and 2-acetylaminofluorene (AAF) by human and rat kidney cells were measured. A slicing technique followed by enzyme digestion was utilized to obtain the kidney cells. Although levels of total metabolism of B(a)P by rat and human kidney cells were similar, analysis of specific metabolites of B(a)P indicated that species differences existed. Human kidney cells produced the organic-soluble metabolites B(a)P-9,10-diol, B(a)P-4,5-diol, B(a)P-7,8-diol, B(a)P-3,6-quinone, and B(a)P-9-phenol. Rat kidney cells produced organic-soluble B(a)P-pre-9,10 diols, B(a)P-9,10-diol, B(a)P-4,5-diol, and B(a)P-6,12-quinone. Both species produced sulfate and glucuronide conjugates of all products. For AAF, kidney cells from some human tissues produced up to four times the level of total metabolites compared to rat kidney cells. Organic-soluble metabolites were qualitatively similar between the species and consisted of 2-aminofluorene (AF), N-hydroxy-AAF and ring-hydroxylated products at the 1, 3, 5/9, 7, and 8 positions. Sulfate and glucuronide conjugates of these metabolites were also detected. Human interindividual variation with kidney cells was about 2.5-fold for total AAF metabolism and up to 6-fold for individual AAF metabolites. For B(a)P metabolism, human interindividual variation in total metabolism was low while for specific metabolites there was up to a 4-fold variation. Levels of AAF and AF cell-mediated Salmonella typhimurium mutagenesis were significantly higher with human cells as compared to rat kidney cells. It appears that the differences between human and rodent kidney cell metabolism of chemical carcinogens vary with the chemical class and understanding these differences will be necessary in the extrapolation of rodent carcinogenesis data to humans. PMID- 2917351 TI - Protection by cycloheximide against cytotoxicity induced by vincristine, colchicine, or delta 12-prostaglandin J2 on human osteosarcoma cells. AB - We examined the protective effects of cycloheximide against cytotoxicity induced by vincristine, colchicine, delta 12-prostaglandin J2, or other antitumor agents on the human osteosarcoma cell line, KSu. Vincristine at a concentration of 0.5 microgram/ml decreased the initial cell number to 34% during 4 days; however, when cycloheximide (0.5 to 10 micrograms/ml) was coexistent, the decrease of the cell number was suppressed and 68% of the initial cells remained viable at the maximum. Furthermore, 0.1 micrograms/ml of cycloheximide also reduced cytotoxicity of colchicine (0.1 to 5 microM) or delta 12-prostaglandin J2 (1 to 5 micrograms/ml) and reduced the cytotoxicity of 0.1 microgram/ml of doxorubicin or 1 micrograms/ml of mitomycin C, suggesting that protection by cycloheximide is shown against cytotoxicity of various types of antitumor agents even on human malignant cells. Next, protein synthesis was reduced to 52% of a control at 3 h by 0.1 micrograms/ml of cycloheximide, suggesting that protein synthesis inhibition precedes the protection. De novo protein synthesis analysis showed that vincristine (0.5 microgram/ml) does not induce any specific protein, whereas delta 12-prostaglandin J2 (3 or 4 micrograms/ml) induced Mr 70,000 and 90,000 proteins, and these were markedly inhibited by cycloheximide (0.1 microgram/ml). In a cell-cycle study, M-phase arrest by vincristine (0.5 microgram/ml) was inhibited in the presence of 0.1 microgram/ml of cycloheximide, suggesting that cell cycle arrest by cycloheximide may be important for protection. From these data, this protection by cycloheximide seems to be more general than expected before. PMID- 2917352 TI - Allele loss at the c-Ha-ras1 locus in human ovarian cancer. AB - Recent reports have shown allele loss at the c-Ha-ras1 locus on the short arm of chromosome 11 in some types of tumors. To determine whether loss of heterozygosity occurs at the c-Ha-ras1 locus in uncultured human ovarian carcinomas we used Southern blot analysis to study DNA from 17 pairs of ovarian tumors and matched white blood cell samples from the same patients. In one of these 17 tumors, the c-Ha-ras1 locus was rearranged, and in five tumor DNAs from ten informative patients, a c-Ha-ras1 allele was lost. This loss, of relatively high incidence, appears to be an important characteristic of human ovarian cancer and may provide a useful tool for understanding its biological behavior. PMID- 2917353 TI - Foci of aberrant crypts in the colons of mice and rats exposed to carcinogens associated with foods. AB - Aberrant crypt foci can be identified in the colons of rodents treated 3 wk earlier with azoxymethane, a known colon carcinogen. These crypts can easily be visualized in the unsectioned methylene blue-stained colons under light microscopy, where they are distinguished by their increased size, more prominent epithelial cells, and pericryptal space. They occur as single aberrant crypts or as two, three, or four aberrant crypts in a cluster. We compared the reported ability of carcinogens associated with the human diet to induce colon cancer with the measured rate of induction of aberrant crypts in female CF1 mice and Sprague Dawley rats. The carcinogens used were 1,2-dimethylhydrazine, methyl nitrosourea, N-nitrosodimethylamine, benzo(a)pyrene, aflatoxin B1, 2-amino-6 methyldipyrido[1,2-alpha:3',2'-d]imidazole, 2-amino-3-methylimidazo[4,5 P]quinoline, 2-amino-3,4-dimethylimidazo[4,5-P]quinoline, and 3-amino-1-methyl-5H pyrido[4,3-b]indole. Graded doses of these compounds were given to the animals by gavage twice with a 4-day interval, and the animals were terminated 3 wk later. All colon carcinogens induced aberrant crypts in a dose-related fashion. N Nitrosodimethylamine and 3-amino-1-methyl-5H-pyrido[4,3-b]indole, carcinogenic compounds that do not induce colon cancer, did not induce them. The ability of the studied compounds to induce aberrant crypts was species specific; e.g., aflatoxin B1 and 2-amino-3,4-dimethylimidazo[4,5-P]quinoline induce about 20 times more in rats than mice. This relationship was consistent with their reported ability to induce colon cancer in these species. Results of the present study support the use of the aberrant crypt assays to screen colon-specific carcinogens and to study the process of colon carcinogenesis. PMID- 2917354 TI - Effects of estradiol on prolactin and growth hormone messenger RNAs in cultured normal and neoplastic (MtT/W15 and GH3) rat pituitary cells. AB - The effects of 17 beta-estradiol (E17 beta) on prolactin (PRL) cell proliferation and on the expression of PRL and growth hormone (GH) proteins and mRNAs were analyzed in cultured pituitary cells by immunocytochemistry, in situ hybridization, and Northern blot hybridization studies. Three different cell cultures were used: (a) normal pituitary cells; (b) GH3 tumor cell line; and (c) MtT/W15, a transplantable PRL and GH-producing pituitary tumor. E17 beta (10(-7) M) caused a significant increase in PRL cell proliferation in normal pituitary [3.9 +/- 0.4 versus 7.7 +/- 0.9% (SEM) of immunostained PRL cells with thymidine incorporation] [P less than 0.01] but produced a significant decrease in PRL cell proliferation in MtT/W15 primary cell cultures [6.7 +/- 1.0 versus 3.7 +/- 0.8%] [P less than 0.05]. PRL mRNA was significantly increased in normal pituitary and in GH3 tumor cells by E17 beta treatment. There was a significant decrease in PRL mRNA and an increase in GH mRNA expression in cultured MtT/W15 tumor cells by immunocytochemistry and in situ hybridization analyses. The percentage of cells producing both PRL and GH or mammosomatotropic cells analyzed by two different techniques declined after one week in culture in normal pituitary cells and in cultured MtT/W15 tumor cells after E17 beta treatment. These results show that E17 beta has a direct stimulatory effect on normal pituitary and GH3 cells and a direct inhibitory effect on MtT/W15 tumor cells with respect to cell proliferation and PRL hormone and mRNA expression. PMID- 2917355 TI - Effects of hyperthermia on chromatin condensation and nucleoli disintegration as visualized by induction of premature chromosome condensation in interphase mammalian cells. AB - The effects of hyperthermia on chromatin condensation and nucleoli disintegration, as visualized by induction of premature chromosome condensation in interphase mammalian cells, was studied in exponentially growing and plateau phase Chinese hamster ovary cells. Exposure to heat reduced the ability of interphase chromatin to condense and the ability of the nucleolar organizing region to disintegrate under the influence of factors provided by mitotic cells when fused to interphase cells. Based on these effects treated cells were classified in three categories. Category 1 contained cells able to condense their chromatin and disintegrate the nucleolar organizing region. Category 2 contained cells able to only partly condense their chromatin and unable to disintegrate the nucleolar organizing region. Category 3 contained cells unable to condense their chromatin and unable to disintegrate the nucleolar organizing region. The fraction of cells with nondisintegrated nucleoli increased with increasing exposure time at 45.5 degrees C and reached a plateau at almost 100% after about 20 min. Exponentially growing and plateau phase cells showed similar response. Recovery from the effects of heat on chromatin condensation and disintegration of the nucleolar organizing region depended upon the duration of the heat treatment. For exposures up to 15 min at 45.5 degrees C, a gradual reduction in the fraction of cells with nondisintegrated nucleoli was observed when cells were allowed for repair at 37 degrees C. However, only a very limited amount of repair was observed after a 30-min exposure to 45.5 degrees C. The repair times observed at the chromosome level were similar to those reported for the removal of excess protein accumulating in chromatin or the nuclear matrix, suggesting a causal relationship between the two phenomena. It is proposed that nuclear protein accumulation on chromatin or in the nuclear matrix reduces the accessibility of chromatin to enzymes responsible for the phosphorylation reactions necessary for chromatin condensation and disintegration of the nucleolus. PMID- 2917356 TI - Analysis of the antigenic profile of uveal melanoma lesions with anti-cutaneous melanoma-associated antigen and anti-HLA monoclonal antibodies. AB - The reactivity of 12 surgically removed uveal melanoma lesions with monoclonal antibodies (MoAb) to 14 membrane-bound and 2 cytoplasmic cutaneous melanoma associated antigens (MAA), to the 2 subunits of HLA Class I antigens and to the gene products of the HLA-D region was compared with that of cutaneous melanoma lesions and correlated with their histiotype. The membrane-bound determinants defined by the anti-Mr 92,000 and 45,000 MAA MoAb TP39.1, anti-Mr 110,000 MAA MoAb M111, anti-Mr 118,000 MAA MoAb TP36.1, anti-Mr 115,000 MAA MoAb 345.134, anti-ICAM-1 MoAb CL203.4 and anti-Mr 31,000 MAA MoAb M2590, and the cytoplasmic determinants defined by the anti-MAA MoAb 465.12 and 2G-10 display a distribution in uveal melanoma lesions similar to that in cutaneous melanoma lesions. On the other hand, membrane-bound determinants defined by the anti-Mr 100,000 MAA MoAb 376.96, anti-9-O-acetyl-GD3 ganglioside MoAb ME311 and anti-GD2-GD3 ganglioside MoAb ME361 were not detected in the uveal melanoma lesions tested. Furthermore, the membrane-bound determinants defined by the anti-GD3 MoAb R24, anti-nerve growth factor receptor MoAb ME20.4, anti-Mr 97,000 MAA MoAb 140.240, anti carcinoembryonic antigen MoAb B1.1 and anti-HMW-MAA 149.53, 225.28, and 763.74 have a markedly lower expression in uveal than in cutaneous melanoma lesions. Incubation of uveal melanoma lesions with the pool of the MoAb 149.53, 225.28, and 763.74 recognizing distinct and spatially distant determinants of the HMW-MAA increased the intensity of staining of six lesions and stained four lesions which were not stained by the individual monoclonal antibodies. The distribution of HLA Class I antigens in uveal melanoma lesions resembles that in cutaneous melanoma lesions, since they are expressed in all the lesions of the mixed and epithelioid type but were not detected in those of the spindle type, i.e., the counterparts of nevocellular nevi. HLA Class II antigens are expressed with a lower frequency in uveal than in cutaneous melanoma lesions, since they were detected only in 2 of the 12 lesions. One of them is of the mixed type and the other one of the epithelioid type. Besides HLA antigens the determinants defined by the anti carcinoembryonic MoAb B1.1, anti-ICAM-1 MoAb CL203.4, and anti-GD3 MoAb R24 displayed a differential distribution in the different histiotypes of uveal melanoma, since they are preferentially expressed in lesions of the mixed and epithelioid type. PMID- 2917357 TI - Specific cytogenetic abnormalities in two new human colorectal adenoma-derived epithelial cell lines. AB - Two new epithelial cell lines from sporadic human colorectal adenomas designated S/AN and S/RG are reported. S/AN was from a villous adenoma and S/RG from a tubular adenoma. Both cell lines have extended growth capacities in vitro reaching passages 18 and 15, respectively, so far and show no signs of senescence. S/AN and S/RG have retained in vitro the ability to form mucin producing goblet-like cells. Every cell of S/AN has a deletion on the short arm of chromosome 1 and one normal copy of chromosome 1. S/AN is also monosomic for chromosome 18. The majority of cells of S/RG only have one normal copy of chromosomes 6, 7, 14, 17, 18, and 22. S/RG also has several marker chromosomes. Although aneuploid S/AN and S/RG are nontumorigenic in athymic nude mice, these cytogenetic abnormalities are insufficient for the fully tumorigenic phenotype. The common abnormality for S/AN and S/RG is monosomy for chromosome 18, indicating that this is a central and important step in colorectal carcinogenesis. Our cytogenetic analysis of the adenoma cell lines suggests at least two possible routes by which premalignant colonic cells can develop and progress to malignancy. S/RG, unlike most other adenoma cell lines, is clonogenic. Aneuploidy, clonogenicity, and extended in vitro growth capacity may therefore be useful in vitro markers for adenoma cell lines with a relatively high malignant potential. PMID- 2917359 TI - Antigenic differences between metastatic and nonmetastatic BSp73 rat tumor variants characterized by monoclonal antibodies. AB - Variants AS and ASML of the BSp73 rat tumor differ markedly with respect to morphology and to the capacity for spontaneous metastasis via the lymphatics. Monoclonal antibodies (MAbs) were raised in order to identify surface molecules associated with both phenotypes. Mice were immunized with either whole cells or isolated membranes and hybridoma supernatants were screened according to the criteria of selective binding to cultured cells of the variant used for immunization. Of two MAbs reacting with the nonmetastasizing AS variant, one showed immunostaining of AS tissue. From 11 MAbs binding to the metastatic ASML variant, 6 showed specific staining of ASML tissue, while the remaining 5 MAbs showed cross-reaction with normal rat tissues. According to Western blot data, the 6 MAbs selectively binding to ASML tissue identified at least 2 different antigens, one of them showing up as a complex of 12 bands. PMID- 2917358 TI - Varied differentiation responses of human leukemias to bryostatin 1. AB - Bryostatin 1, a macrocyclic lactone isolated from a marine bryozoan, has significant antineoplastic activity against the murine cell line P388. Like phorbol esters, bryostatin 1 is capable of binding to and activating protein kinase C, but these two compounds differ in the ability of bryostatin 1 to act as a tumor promoter. We have investigated whether bryostatin 1 can modulate the differentiated phenotype of fresh samples of human myeloid leukemia. We find that six of seven samples responded to bryostatin treatment with changes associated with a more differentiated phenotype including increases in macrophage-like morphology and an increase in adherence and OKM1 and alpha-naphthyl acetate esterase activity positivity. The percentage of cells within each sample evidencing these changes varied markedly among the seven patients' cells examined. Because of the effects of bryostatin on fresh samples we examined the ability of bryostatin to differentiate four HL-60 cell sublines obtained from different laboratories. We found that two of the cell lines did not respond either with an inhibition of growth or morphological change, while one was inhibited, and one showed both growth inhibition and some induction of macrophage like morphology when treated with bryostatin. To test whether other differentiating agents would enhance the effects of bryostatin 1, we added tumor necrosis factor alpha and bryostatin to these four cell lines. The addition of both agents effected an additive inhibition of growth. These data suggest that bryostatin 1 alone or in combination with other biological response modifiers may have a role in the treatment of human leukemia. PMID- 2917360 TI - Dose-related endocrine effects and pharmacokinetics of oral and intramuscular 4 hydroxyandrostenedione in postmenopausal breast cancer patients. AB - 4-Hydroxyandrostenedione (CGP32349; 4-OHA) is a clinically effective treatment for advanced postmenopausal breast cancer by both the parenteral and p.o. routes, as a result of its inhibition of aromatase and consequent suppression of plasma estrogen levels. Thirty patients were randomized to treatment with 250 mg 4-OHA orally once, twice, and 4 times daily for 2 weeks and 29 of these plus a further 11 patients were then randomized to treatment with 250 or 500 mg i.m. every 2 weeks to determine the optimal dose for each route according to the suppression of serum estradiol levels. There was no significant difference between the 3 oral doses in their suppression of estradiol levels indicating that the maximum required p.o. dose of 4-OHA is probably 250 mg daily. Suppression by the parenteral dose of 250 mg every 2 weeks was marginally suboptimal but clinical considerations of response and tolerability indicate this as the optimal dose for i.m. injection. 4-OHA had no effect on serum levels of androstenedione, testosterone, or 5 alpha-dihydrotestosterone when given by either route but p.o. treatment with 4 doses of 250 mg daily reduced sex hormone-binding globulin levels by a mean of 34%. Serum levels of estrone as measured by gas chromatography-mass spectrometry were suppressed to approximately 40% of baseline by parenteral treatment. The half-life of 4-OHA p.o. was approximately 3 h, whereas the apparent half-life of injected drug was between 5 and 10 days after a more rapid clearance during the first 4 days after injection. PMID- 2917361 TI - Case-control study of colorectal cancer and fecapentaene excretion. AB - The fecapentaenes are potent mutagens found in high concentrations in the stools of some individuals. These compounds are produced in vivo by common species of the colonic microflora, from precursors of unknown origin. The fecapentaenes have been postulated to increase the risk of colorectal cancer. To test this hypothesis, we measured fecapentaene excretion in 69 patients with adenocarcinoma of the colon or rectum, newly diagnosed at three Washington, DC area hospitals. The cases were compared with 114 surgical controls, frequency matched to the cases on age, sex, and hospital. We attempted to measure fecapentaene excretion 4 times for each subject: before surgery; and at 1 mo; 3 mo; and 6 mo following surgery. Contrary to our study hypothesis, we found fecapentaene excretion during the four study periods to be similar or even lower in cases compared to controls. An indirect measurement of fecapentaene precursors also tended to be lower in cases. The case-control differences could not be explained as effects of bleeding or of the colorectal diagnostic workup, which was assessed in a separate group of 86 patients. We conclude from these data that the excretion of fecapentaenes does not increase the risk of colorectal cancer, at least when measured near the time of diagnosis. PMID- 2917362 TI - Conference on advances in the biology and chemistry of N-nitroso and related compounds. PMID- 2917364 TI - Cell-mediated immunity is enhanced by cytostatic drugs continuously released at the site of antigenic stimulation. AB - Immunopotentiation by cytostatic drugs continuously released from osmotic minipumps, was investigated in a guinea-pig contact-sensitivity model. These pumps are designed to release their content within a period of 7 days. Vepeside (VP-16) and 5-fluorouracil were released into oxazolone-stimulated lymph nodes by subcutaneous implantation of pumps containing either of these drugs. The pumps were implanted at the intended sensitization site, 2 days before sensitization. Strong potentiation of T-cell-mediated immunity, evaluated by delayed-type hypersensitivity measurements, was observed with both drugs tested. Daily injections with VP-16 also caused an enhancement of the immune response. However, daily injections with 5-fluorouracil, a drug assumed to be cell-cycle-specific in its action, failed to potentiate delayed hypersensitivity to oxazolone. Intralesional administration of cytostatic drugs has been put forward as an effective treatment modality in various types of cancer. Therapeutic effects may depend on both local tumor cytotoxic and immunopotentiating activities. Our present results suggest that osmotic minipumps can be applied to broaden the applicability and effectiveness of local chemotherapy. PMID- 2917363 TI - Endogeneous interferon alpha/beta produced by murine Kupffer cells augments liver associated natural killing activity. AB - Nonparenchymal liver cells from untreated C3HeB/FeJ mice, when incubated in medium containing-10% fetal bovine serum or portal serum, produced significant amounts of interferon alpha/beta (IFN alpha/beta). In contrast, other cell populations (spleen, mononuclear blood cells and peritoneal cells) from C3HeB/FeJ mice or nonparenchymal liver cells from other strains of mice (C3H/HeJ, germ-free C3H/HeN and C57Bl/6J) produced little or no detectable IFN in fetal bovine serum under the same culture conditions. The cells in the nonparenchymal liver cell population responsible for IFN alpha/beta production were adherent, phagocytic, silica-sensitive, carbonyl-iron-sensitive, and Thy1.2-, presumably Kupffer cells or resident liver macrophages. IFN alpha/beta production by cultured Kupffer cells was not observed if medium containing fetal bovine serum or portal serum was treated with polymyxin B or if Kupffer cells were cultured in serum-free medium. This suggested that small amounts of endotoxin in fetal bovine or portal serum stimulated Kupffer cells to produce IFN alpha/beta. Possibly, Kupffer cells are in a different state of activation/maturation than peritoneal and splenic macrophages since the sensitivity of resident Kupffer cells from C3HeB/FeJ mice to the stimulatory effects of endotoxin. The endogenous production of IFN alpha/beta by Kupffer cells from C3HeB/FeJ mice can augment liver-associated natural killer (NK) activity against YAC-1 cells (4h) and induce liver-associated cytotoxic activity, not restricted by the major histocompatibility complex, against NK resistant P815 mastocytoma cells (18 h). PMID- 2917365 TI - In vitro modulation of natural killer cell activity in non-Hodgkin's lymphoma patients after therapy. AB - The depressed natural killer (NK) activity, anti-body-dependent cellular cytotoxicity (ADCC) and NK cytotoxic factor cytotoxicity in untreated non Hodgkin's lymphoma patients were found to be elevated after chemotherapy. In vitro treatment of the effector NK cells with interferon alpha could augment the NK activity in normal subjects and treated patients to a comparable degree. Chemotherapy mainly affected the post-binding events in the NK cytotoxic process by causing an increase in the active killing potential of the NK cells. This study provides a better understanding of changes in the NK cytotoxic mechanism in non-Hodgkin's lymphoma patients and the role of interferon in this process. PMID- 2917366 TI - Five intermediate complexes in transcription initiation by RNA polymerase II. AB - A native gel electrophoresis DNA binding assay was used to resolve complexes formed on the adenovirus Major Late Promoter by general transcription factors and RNA polymerase II. Five sets of complexes containing distinct components were identified. These complexes were generated by sequential binding of TFIID, TFIIA, TFIIB, RNA polymerase II, and TFIIE. The relative positions of each of the factors in the complexes were determined by DNAase I footprint analysis. TFIIA, derived from yeast or mammalian cells, formed a complex with yeast TFIID and the TATA element. TFIIB bound to this complex and probably acts as a "bridge" to the polymerase and the initiation site. The addition of ATP or dATP, necessary for "activation" of transcription, resulted in an alteration of the footprint in the +20 to +30 region, the same area protected upon addition of TFIIE to the initiation complex. Addition of ribonucleotide triphosphates generated new complexes that contained accurately initiated transcripts associated with the transcription machinery and the template DNA. A model for the interactions of components in initiation of transcription by RNA polymerase II is proposed. PMID- 2917367 TI - Trypanosoma brucei contains two RNA polymerase II largest subunit genes with an altered C-terminal domain. AB - We have identified and cloned four trypanosomal RNA polymerase largest subunit genes. Here, we present the molecular analysis of two genes, Trp4.8 and Trp5.9. The sequence of these genes shows that they are almost identical to each other and indicates that they encode the largest subunit of RNA polymerase II. Both genes contain a C-terminal extension that is clearly distinct from that of other eukaryotic RNA polymerase II genes, because it lacks the common tandemly repeated heptapeptide sequence and is rich in acidic amino acids. It shares many potential phosphorylation sites, however, with the C-terminal extension of other eukaryotic RNA polymerase II large subunits. The presence of two RNA polymerase II loci suggests that a fourth RNA polymerase could be formed. Interestingly, the fourth gene is only found in species exhibiting antigenic variation. PMID- 2917368 TI - The ultrastructure of upstream and downstream regions of an active Balbiani ring gene. AB - When active, the 37 kb Balbiani ring genes are known to form transcription loops with an almost fully extended chromatin axis. Here we examine the upstream and downstream regions of such transcription loops by electron microscopy. We demonstrate that a loop starts and ends in tightly packed chromatin; the two anchoring sites are clearly separated from each other in space. The upstream, nontranscribed region consists of a thin, extended, apparently flexible and nucleosome-free fiber corresponding to about 0.5 kb DNA. The downstream, nontranscribed region appears as a 200 nm long nucleofilament loosely coiled into a short, thick chromatin fiber and estimated to contain about 3 kb DNA. PMID- 2917369 TI - A role of Ia-associated invariant chains in antigen processing and presentation. AB - Most native antigens require processing in a cellular compartment for efficient presentation to T helper cells. The cellular elements that permit processing are not known. We investigated a possible role of the class II MHC-associated invariant chains in antigen processing. Fibroblast cells that were transfected with class II genes were compared with fibroblasts supertransfected with the invariant chain gene for their capacity to present the fifth component of complement (C5) to C5-specific class II restricted T cell clones or influenza virus protein to a virus-specific T cell clone. Only fibroblasts supertransfected with the invariant chain gene were able to present native antigen, even at very low antigen concentration, whereas both fibroblast types could present cyanogen bromide-fragmented C5 or the virus peptide. Presentation of intact antigen but not of fragmented antigen was totally abrogated by treatment of fibroblasts with chloroquine. The invariant chain gene encodes two polypeptides, li31 and li41. Expression of either li31 or li41 was sufficient to render class II-expressing fibroblasts capable of presenting intact antigen. PMID- 2917370 TI - Thermal skin injury: I. Acute hemodynamic effects of fluid resuscitation with lactated Ringer's, plasma, and hypertonic saline (2,400 mosmol/l) in the rat. AB - Heart rate (HR), central venous pressure (CVP), mean arterial pressure (MAP), and cardiac index (CI) were measured in anesthetized rats subjected to a 40% body surface area full-thickness scald burn. Postburn intravenous fluid therapy with lactated Ringer's (5 ml/hr), plasma (2.5 ml/hr), or very hypertonic saline (2,400 mosmol/l) (0.75 ml/hr) was compared to unburned or burned, untreated controls. HR and CVP were not influenced significantly by thermal injury. MAP decreased steadily in the untreated group from 110 mmHg to 80 mmHg at 3 hr postburn. In the fluid-treated groups MAP did not change significantly. During the first 15 min postburn, CI was reduced to 58-71% of control values (P less than 0.01). CI increased during Ringer's and plasma infusion to 74-80% of control values (P less than 0.02 vs. unburned). Despite infusion therapy, hematocrit increased from 48 to 52%, clearly less than in the unresuscitated group (increase from 48 to 58%). Theoretically, the 2,400 mosmol/l saline would expand extracellular volume by five to six times the infused volume. Still, CI was reduced by 55% at 3 hr postburn in the hypertonic saline as well as in the burned, untreated group (P less than 0.001 vs. unburned). The low CI was mainly due to a reduced stroke volume. PMID- 2917371 TI - Thermal skin injury: II. Effects on edema formation and albumin extravasation of fluid resuscitation with lactated Ringer's, plasma, and hypertonic saline (2,400 mosmol/l) in the rat. AB - Pentobarbital anesthetized rats were subjected to a 40% body surface area full thickness scald burn. Intravenous fluid therapy was given as lactated Ringer's (5 ml/hr), plasma (2.5 ml/hr), or very hypertonic saline (2,400 mosmol/l) (0.75 ml/hr) and compared to unburned or burned, untreated controls. At 3 hr postburn, skin water and albumin content and extravasation of radiolabelled albumin were determined. Water content in injured skin increased by 35-78% (least in the untreated group, most in the plasma group) compared to unburned controls (P less than 0.05). After lactated Ringer's therapy water content increased even in unburned skin and in muscle (P less than 0.05). Tissue albumin mass increased generally slightly more than the increase in water content, from 37% (lactated Ringer's group) to 126% (plasma group) in burned areas. Extravasation rate of radiolabelled albumin increased 5-80 times in burned areas, most following plasma treatment (equivalent to 0.6-1.0 ml plasma/g dry weight/180 min). A major part of the estimated total fluid loss following therapy by lactated Ringer's took place in noninjured tissue. Plasma therapy gave less fluid accumulation in unburned tissues but more edema in the injured areas than lactated Ringer's. PMID- 2917372 TI - Effect of hemorrhagic hypotension on endotoxin-induced lung injury in awake sheep. AB - Pulmonary insufficiency is a major cause for mortality and morbidity following shock and sepsis. We studied the effect of hemorrhagic shock and retransfusion on endotoxin-induced lung dysfunction. Eighteen unanesthetized sheep with chronic lung lymph fistulae were divided into 3 groups. In Group I (n = 5) hemorrhagic shock of 50 torr was induced by arterial bleeding. Shed blood was retransfused after 4 h, and the animals were observed for 5 h. In Group II (n = 7) 1 microgramg/kg E. coli endotoxin was injected intravenously, and the animals were observed for 5 h. In Group III (n = 6) hemorrhagic shock was induced similarly to Group I. After 2 h of hypotension, E. coli endotoxin was injected similarly to Group II. Blood was retransfused after 4 h. During hemorrhagic shock arterial oxygen tension (PaO2) increased from 78.0 to 94.0 torr (P less than 0.005), lymph flow (QL) decreased from 7.2 to 5.2 ml/h (P less than 0.05) and lymph protein clearance (L/P.QL) from 4.6 to 3.3 ml/h (P less than 0.05). Calculated pulmonary microvascular pressure (Pmv) decreased from 11.1 to 7.0 torr (P less than 0.05). Plasma TXB2 increased from 197 to 967 pg/ml (P less than 0.05) and lymph TXB2 from 272 to 833 pg/ml (P less than 0.05). Endotoxin infusion was followed by a fall in WBC to 2,900/microliters (P less than 0.001), rise in pulmonary artery pressure (Ppl) from 17.5 to 49.7 torr (P less than 0.005), and Pmv from 12.1 to 23.7 torr (P less than 0.01). PaO2 decreased from 78.0 to 61.0 torr (P less than 0.01), QL increased to 36.9 ml/h (P less than 0.001), and L/P.QL to 24.3 ml/h (P less than 0.001). Plasma TXB2 increased to 7,600 pg/ml (P less than 0.005) and 6 Keto PGF1 alpha to 1,519 pg/ml (P less than 0.01). Infusion of endotoxin during hemorrhagic shock was followed by a comparable fall in WBC, pulmonary hypertensive response and hypoxemia, while Pmv increased only to 19.2 torr which was significantly lower than Group II (P less than 0.05). The rise in QL to 17.4 and L/P.QL to 10.6 ml/h in response to endotoxin was also significantly lower than Group II (P less than 0.05 and P less than 0.05, respectively). Plasma and lymph TXB2 and 6-Keto PGF1 alpha were unchanged. It is concluded that hemorrhagic shock reduced endotoxin-induced pulmonary microvascular pressure, pulmonary lymph production and protein flux, while the fall in WBC, early pulmonary hypertensive phase, hypoxemia, and prostanoid production were not altered by the hypotensive insult. PMID- 2917374 TI - Effect of voluntary exercise on urinary excretion of catecholamines after traumatic shock in rats. AB - Thirteen rats were kept in cages equipped with running wheels for 10 months (exercise group), and 12 rats were kept in cages without running wheels during the same period (control group). Rats in both groups were subjected to a Noble Collip drum trauma (40 rpm, 350 revolutions in total) after the 10-month conditioning period. Urine output, urinary epinephrine (E), and norepinephrine (NE) were measured until the seventh day after the trauma. Urine output decreased after the trauma in both groups to the same extent, but the recovery of urine output after trauma was accomplished faster in the exercise group than in the control group, and diuresis after trauma was seen only in the exercise group. Urinary E increased in both groups within 24 hours after trauma, but the increase in the exercise group was significantly less than in the control group. The amount of NE excreted depended somewhat on the urine volume, but there was no significant difference in changes in urinary NE after trauma between the groups. These results suggest that rats bred in an active condition suffered less severe traumatic shock accompanied by a reduced sympathoadrenal activity as compared with rats bred in a relatively sedentary condition. PMID- 2917373 TI - Significance of hepatic mitochondrial redox potential on the concentrations of plasma amino acids following hemorrhagic shock in rats. AB - The changes in hepatic energy charge, hepatic mitochondrial redox potential, and plasma amino acid concentrations were examined in rats following the induction of hemorrhagic shock with mean arterial blood pressure at 50 mmHg. Hepatic energy charge and mitochondrial redox potential decreased significantly (P less than 0.001), from 0.86 +/- 0.01 to 0.49 +/- 0.05 and from 14.4 +/- 0.8 to 2.9 +/- 0.6, respectively, at 2 hours after the induction of hemorrhagic shock. Concentrations of total amino acids, alanine, proline, tyrosine, and phenylalanine in plasma increased, and molar ratio [( valine + leucine + isoleucine]/[tyrosine + phenylalanine]) in plasma decreased significantly (P less than 0.001). Hepatic mitochondrial redox potential was correlated negatively with total amino acids (r = -0.90, P less than 0.001) and positively with molar ratio (r = 0.85, P less than 0.001) during hemorrhagic shock. By reinfusion of shed blood at 2 hours after hemorrhagic shock, hepatic energy charge and mitochondrial redox potential immediately recovered to the pretreatment level. However, total amino acids, proline, tyrosine, and phenylalanine increased transiently and thereafter decreased to the pretreatment level. Molar ratio did not recover even at 60 minutes after reinfusion. These results suggest that, in hemorrhagic shock, reduced hepatic mitochondrial redox potential causes inhibition of the citric acid cycle metabolizing the amino acids in the liver and an increase of plasma amino acids; these results suggest also that, in the recovery phase from shock, the restoration of hepatic mitochondrial redox potential is a prerequisite for normalization of the accumulated plasma amino acids. PMID- 2917375 TI - The role of intestinal endotoxin in experimental peritonitis. AB - Escape of endotoxin from the intraintestinal site was investigated in experimental models of intestinal ischemia and during intraabdominal infection in rats. Following the instillation of Salmonella abortus equi endotoxin (S-form) into the proximal large bowel, we recorded the presence of the lipopolysaccharide molecule in the bowel wall, the intestinal lymph nodes, the peritoneal cavity, and in the liver sinusoids by immunohistochemical methods. At 3, 6, 12, 24, and 48 hr after the operative procedure, peritoneal fluid, blood, and tissue samples were taken. Survival rates were similar between the two test-groups (occlusion of the superior mesenteric artery [SMA] and cecal ligation and puncture [CLP]) and were not influenced by the amount of the injected endotoxin. There was no detectable morbidity in the sham-operated control animals with endotoxin doses up to 20 mg. Endotoxin could only be detected at 24 and 48 hr in the SMA group in the liver as well as in the peritoneal sediment and in intestinal lymph nodes. CLP and control samples remained negative throughout the observation period. Bacteria were found intraperitoneally within 12 to 24 hr in the SMA group and within 3 to 12 hr in the CLP group. PMID- 2917376 TI - Real-time and simultaneous measurement of tricuspid orifice and tricuspid anulus areas in anesthetized dogs. AB - Tricuspid valve orifice and tricuspid valve anulus areas were measured simultaneously in the anesthetized dog with a newly developed area-measuring system based on electromagnetic induction. This system permitted real-time monitoring of the area enclosed by the edges of valve leaflets and by the juncture of the valve leaflet and the cardiac wall in situ, without artificial constraint to the valve motion. Right atrial and right ventricular pressures were measured with two catheter-tipped micromanometers. During control state, tricuspid valve orifice area (TOA) increased up to its peak [1.38 +/- 0.26 cm2 (mean +/- SD)] coincidently with either atrial systole or rapid ventricular filling. Atrial contraction evoked distinct presystolic tricuspid anulus narrowing with concomitant slow TOA reduction. This slow TOA reduction began 30.0 +/- 16.1 msec before systolic atrioventricular pressure crossover, and the following rapid TOA decrease was completed 38.7 +/- 12.2 msec after systolic atrioventricular pressure crossover. TOA began to increase 48.4 +/- 30.4 msec before diastolic atrioventricular pressure crossover at the end portion of the isovolumic relaxation phase, opposing residual transvalvular pressure gradient (3.33 +/- 1.79 mm Hg). The slow presystolic TOA decrease was considered to be a reflection of the presystolic anulus narrowing caused by atrial systole. An isolated atrial contraction induced by administering 1 mg acetylcholine chloride into the atrioventricular node artery or by vagus nerve stimulation could produce complete valve closure. Even in an isolated atrial contraction, the inflection point that marks the boundary between slow "atriogenic" closure presumably due to anulus narrowing and rapid closure presumably due to hemodynamic force was easily identified. PMID- 2917377 TI - Protection against autonomic denervation following acute myocardial infarction by preconditioning ischemia. AB - To examine the effects of ischemic preconditioning on efferent autonomic responses following acute transmural myocardial ischemia/infarction (MI), the time course and extent of efferent sympathetic and vagal denervation were compared between control dogs that received a one-stage sustained coronary occlusion and preconditioned dogs that received four 5-minute coronary occlusions separated by 5 minutes of reperfusion before sustained occlusion. Effective refractory periods (ERP) basal and apical to MI were determined in the baseline state and during neural stimulation before and after preconditioning occlusions and 20, 60, 120, and 180 minutes after sustained occlusion by ligature ligation of diagonal branches of the left anterior descending coronary artery. In 10 control dogs with transmural MI, ERP shortening induced by bilateral ansae subclaviae stimulation (4-msec pulses, 2-4 Hz and 2-4 mA) was unchanged at basal sites but was attenuated at apical sites. Four of 40 apical test sites exhibited efferent sympathetic denervation (less than or equal to 2 msec shortening) 20 minutes after sustained occlusion. Thirteen of 40 apical sites became denervated during a 3-hour period. In 10 preconditioned dogs, ERP shortening at apical sites was unchanged after preconditioning occlusions and during the first 60 minutes of sustained ischemia but was attenuated at 120 minutes. Three of 40 apical test sites became denervated during a 3-hour period. The cumulative percentage of denervated apical test sites was significantly less in the preconditioned group compared with the control group (p = 0.006) despite a comparable degree of subepicardial involvement in the MI (8.2 +/- 1.0% vs. 8.4 +/- 1.4%, the ratio to the left ventricular circumference, mean +/- SEM). In 11 control dogs tested for efferent vagal response after MI, ERP prolongation induced by bilateral vagal stimulation (4-msec pulses, 20 Hz with current strength 0.05 mA greater than that required to produce asystole) was unchanged at basal sites, but was attenuated at apical sites, and five of 44 test sites exhibited denervation (less than or equal to 1 msec prolongation) 20 minutes after sustained coronary occlusion. Fourteen of 40 apical sites became denervated during a 3-hour period. In 10 preconditioned dogs, vagally induced ERP prolongation was unchanged both at basal and apical sites, and none of 36 apical test sites exhibited denervation after preconditioning and during a 3-hour period of sustained coronary occlusion (p less than 0.001 vs. control group) despite a comparable degree of subendocardial involvement in the MI (11.8 +/- 0.8% vs. 11.9 +/- 1.3%).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2917378 TI - Estimating cardiac transmembrane activation and recovery times from unipolar and bipolar extracellular electrograms: a simulation study. AB - A model of one-dimensional action potential propagation was used to compare activation times and recovery times measured from simulated unipolar and bipolar electrograms with the activation and recovery times measured from simulated transmembrane action potentials. Theory predicts that the intrinsic deflection- the time of the maximum negative slope of the unipolar electrogram QRS complex- corresponds to the time of maximum positive slope of action potential depolarization. Similarly, the time of the maximum positive slope of the unipolar electrogram T wave corresponds to the time of maximum negative slope of action potential repolarization. This study showed that the difference between the unipolar electrogram activation time and the action potential activation time and the difference between the unipolar electrogram recovery time and the action potential recovery time were small during ideal conditions of uniform propagation in a long cable. Nonideal conditions, however, were associated with activation time differences in excess of 1.8 msec and recovery time differences in excess of 30 msec (243 msec in certain conditions). Nonideal conditions that had a major influence were changes in activation sequence, propagation in a short cable, and propagation through regions of nonuniform coupling resistance and/or nonuniform membrane properties. Nonideal conditions that had a smaller influence were variations in distance from the measurement site to the simulated tissue surface, nonzero reference potentials, and the addition of distant events. Recovery time differences were more sensitive to the nonideal conditions than were activation time differences, and both depended on the action potential shape. When distant events significantly contributed to the unipolar electrogram waveform, the time differences when bipolar electrograms were used were less than those when unipolar electrograms were used; however, under other conditions, the time differences were comparable. Results showed that activation times and especially recovery times measured from electrograms can be greatly affected by conditions independent of changes in the underlying action potential waveforms. PMID- 2917379 TI - Effect of oxygen withdrawal on active and passive electrical properties of arterially perfused rabbit ventricular muscle. AB - Oxygen withdrawal from myocardial cells leads to changes of the transmembrane action potential (mainly action potential shortening), to cellular uncoupling, and to changes of vascular permeability. This study was aimed at the simultaneous measurement of electrical activity and passive electrical properties (extracellular and intracellular longitudinal resistance) in arterially perfused rabbit papillary muscles under different conditions of changed oxygen supply. These included 1) complete anoxia (erythrocyte-free perfusate), 2) hypoxia (PO2 between 23-28 mm Hg, erythrocytes present) in the presence and absence of glucose, and 3) normoxia with erythrocyte-free perfusate. Similarly to myocardial ischemia, rapid cellular uncoupling occurred only after an initial stable period of approximately 17 minutes, and it required complete anoxia. The marked shortening of the action potential developed before cellular uncoupling. In six out of eight experiments, the fibers were inexcitable when uncoupling started. In severe hypoxia, no significant change of internal longitudinal resistance was observed over 35-40 minutes. The time course of the extracellular longitudinal resistance was different from the change in intracellular resistance: A marked decrease occurred almost immediately after the onset of oxygen withdrawal. This decrease was followed by a small increase in conduction velocity, which was most likely due to a change in the interstitial compartment (edema). It was observed during anoxic as well as during hypoxic perfusion. We conclude that 1) cellular uncoupling in arterially perfused tissue requires almost complete oxygen lack and occurs with a delay of more than 10 minutes, 2) marked action potential shortening precedes uncoupling, and therefore can not simply be attributed to an increase in free, intracellular calcium, and 3) vascular endothelial function is more sensitive to oxygen withdrawal than the myocyte. PMID- 2917380 TI - Cardiac sympathetic afferent cell bodies are located in the peripheral nervous system of the cat. AB - Studies of the stellate ganglion and middle cervical ganglion indicate that sympathetic efferent nerve activity can be modified by peripheral excitatory inputs and that these neural connections may function as pathways for a peripheral reflex at the level of the thoracic sympathetic ganglia. This excitatory synaptic input could have a soma in either the central or the peripheral nervous system. A study was designed to determine whether chronic decentralization (3 weeks) of the stellate ganglion in cats would 1) abolish sympathetic cardiac afferent nerve activity recorded at the stellate cardiac nerve and 2) abolish local thoracic reflexes that are generated by stimulation of peripheral nerves. The ansae subclaviae, T3 and T4 rami, and stellate ganglion were also examined by electron microscopy for the extent of Wallerian degeneration. Afferent cardiac activation of the axon collaterals arising from cell bodies located in the dorsal root ganglia was abolished due to degeneration. However, sympathetic afferent nerve activity from the left ventricular receptors was still present and was recorded from the stellate cardiac nerve in all cats. Cardiac receptors were sensitive to mechanical distortion, increases in the left ventricular pressure, and epicardial application of veratrine hydrochloride. These data imply that 1) cardiovascular afferent input to the stellate ganglion persists following chronic decentralization and 2) the sensory neurons are located in the peripheral sympathetic nervous system. Thus, we find that regulation of the heart occurs in part via thoracic ganglia, independently of the central nervous system. PMID- 2917381 TI - Role of thromboxane A2 in the control of myocardial O2 supply/consumption balance and severity of ischemia during pacing-induced ischemia. AB - The role of thromboxane A2 (TXA2) in the control of O2 supply/consumption variables during pacing-induced ischemia was examined using the TXA2 receptor antagonist SQ 29,548. Anesthetized, open-chest dogs were subjected to left anterior descending coronary artery (LAD) stenosis that produced significant epicardial S-T segment elevation (12 mV) only when superimposed on atrial pacing. Regional myocardial blood flow was determined using radioactive microspheres, and O2 consumption was determined by measuring O2 saturation of venous blood draining the ischemic region. The dogs were treated with saline or 0.2 mg/kg + 0.2 mg/kg/hr SQ 29,548, and the effect on ischemia was determined during 5-minute pacing-induced ischemic episodes at 10, 40, and 70 minutes postdrug or saline treatment. SQ 29,548 significantly reduced S-T elevation at 40 and 70 minutes postdrug compared with saline values and at all times measured compared with its paired predrug pace+stenosis values. SQ 29,548 reduced S-T elevation approximately 45% compared with its paired predrug values at 70 minutes. SQ 29,548 resulted in a significantly higher subendocardial-to-subepicardial flow ratio (0.70 +/- 0.10, p less than 0.05) compared with saline-treated animals (0.42 +/- 0.06), with an overall increase of flow to the ischemic region of approximately 40%. This increased flow was matched by a proportional increase in O2 consumption without a change in O2 extraction. The O2 supply/consumption balance was also unchanged by SQ 29,548 implying that despite the increase in blood flow, the ischemic region was still flow-limited.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2917382 TI - Simultaneous measurements of action potential duration and intracellular ATP in isolated ferret hearts exposed to cyanide. AB - Shortening of the cardiac action potential during ischemia and anoxia is likely to contribute to the decline in contractility that occurs under such conditions. It has been hypothesized that a decrease in the intracellular ATP concentration ([ATP]i) underlies the changes in the action potential. The recently discovered potassium channel activated at low ATP concentrations might provide the link between action potential shortening and low [ATP]i. However, it has yet to be shown that [ATP]i falls to the range required for channel activation at the time when action potential shortening occurs. We have measured action potentials and [ATP]i simultaneously in isolated ferret hearts during inhibition of both oxidative phosphorylation and anaerobic glycolysis (metabolic blockade). Metabolic blockade caused a rapid decline in cardiac contractility, accompanied by a rapid fall in action potential duration. [ATP]i fell only slightly and remained well above the range where activation of the ATP-sensitive K+ channel would be expected to occur. Moreover, reintroduction of glucose to the perfusate led to a substantial recovery in both contraction and in action potential duration, again in the absence of any great change in [ATP]i. These results suggest that the action potential shortening observed in metabolic blockade cannot be explained by the simple hypothesis of K+ channel opening as a consequence of a decrease in bulk [ATP]i unless the Km for suppression of channel activity by ATP is very much higher in intact cells than in any of the patch configurations studied. An alternative explanation is that the channel may be regulated under these conditions by mechanisms other than a change in [ATP]i. PMID- 2917383 TI - Stimulation of renal sympathetic activity by static contraction: evidence for mechanoreceptor-induced reflexes from skeletal muscle. AB - Static muscular contraction in anesthetized animals has been firmly established to reflexly increase arterial pressure. Although group III and IV muscle afferents are known to be responsible for this reflex pressor response, there is no evidence that the stimulation of muscle mechanoreceptors, many of which are supplied by group III fibers, plays a role in causing this contraction-induced reflex effect. To provide this evidence, we recorded renal sympathetic nerve activity in chloralose-anesthetized cats while contracting the triceps surae muscles. We found that static contraction tripled renal nerve activity within three seconds of its onset, an increase that was abolished by cutting the L6 and S2 dorsal roots. On average, the contraction-induced increase in renal nerve activity was observed 0.8 +/- 0.1 seconds after the onset of this maneuver. In addition, intermittent tetanic contractions synchronized renal nerve discharge so that a burst of activity was evoked by each contraction. A similarly synchronized renal nerve discharge was evoked in paralyzed cats by electrical stimulation of the tibial nerve at five times motor threshold, a current intensity that activates group III afferents. We conclude that, in anesthetized animal preparations, mechanoreceptors with group III afferents contribute to the reflex stimulation of renal sympathetic outflow evoked by muscular contraction. PMID- 2917385 TI - Left ventricular time varying elastance behavior does not reflect a basic property of cardiac muscle. PMID- 2917384 TI - Significance of the transmural diminution in regional hydrogen ion production after repeated coronary artery occlusions. AB - Previous studies have revealed that the regional accumulation of ischemic metabolites including hydrogen ion (H+) and PCO2 diminish after repeated occlusions. We postulated that this diminution reflects a blunted metabolic response that is related to the severity of ischemic injury and, hence, may be most pronounced in subendocardial (ENDO) regions. To investigate this hypothesis, the left anterior descending coronary artery was serially occluded three times in 51 dogs for a period of either 3 minutes (n = 15), 5 minutes (n = 18), or 15 minutes (n = 18). Each occlusion was separated by 45 minutes of reperfusion. Myocardial [H+] was measured in the endomyocardium and in the epimyocardium of the ischemic anterior wall by use of miniature pH glass electrodes. Accumulation of H+ during occlusion (delta [H+]) in the ENDO region was significantly less during the second occlusion when compared with the first occlusion (3-minute occlusions: 28.2 +/- 3.7 nM/l vs. 39.4 +/- 5.4 nM/l, p less than 0.002; 5-minute occlusions: 49.8 +/- 5.0 nM/l vs. 72.1 +/- 6.5 nM/l, p less than 0.0002; 15 minute occlusions: 132.3 +/- 14.6 nM/l vs. 225.6 +/- 27.7 nM/l, p less than 0.0003). A similar trend was noted for delta [H+] in the subepicardial (EPI) regions. During occlusion, the rise in [H+] occurred sooner, and delta [H+] was consistently greater in the ENDO when compared with the EPI regions (p less than 0.05). Regional myocardial blood flow did not change during the three occlusions, indicating that the diminution in H+ accumulation stemmed from a decrease in H+ production and not from an increase in collateral flow. The decrement in H+ accumulation between the first and second occlusions (delta [H+]1-delta [H+]2) 1) was greater in the ENDO than in the EPI regions (p less than 0.05); 2) correlated with the duration of occlusion (ENDO: r = 0.66, p less than 0.001; EPI: r = 0.82, p less than 0.0001); and 3) was related to the impairment of anterior wall systolic shortening after the first reperfusion period. These findings suggest that the diminution in H+ production that follows serial coronary occlusions reflects a blunted metabolic response that is related to both the duration of ischemia and the degree of systolic dysfunction. Moreover, though attenuation of ischemic metabolite production occurs transmurally, it is most pronounced in the deep ENDO regions. PMID- 2917386 TI - Transcoronary chemical ablation of ventricular tachycardia. AB - After identification of the artery supplying blood to the arrhythmogenic area, transcoronary chemical ablation of ventricular tachycardia was undertaken in three patients with incessant tachycardia in whom the other therapeutic options had failed. Sterile ethanol (96%) was given at a dose of 1.5 ml in two patients and a total of 6 ml in the third. The arrhythmia was cured in two patients and suppressed during a 1-month period in the third until new collateral blood supply to the arrhythmogenic area developed and ventricular tachycardia recurred. The procedure was then repeated successfully. After administration of ethanol in the high interventricular septum, one patient developed temporary complete atrioventricular block and a pacemaker was implanted. No other complications occurred. We observed that in patients with ventricular tachycardia after myocardial infarction, it is possible to identify and catheterize small coronary arteries responsible for blood supply to the site of origin or pathway of ventricular tachycardia. After careful transcoronary mapping with saline, chemical ablation can prevent further episodes of the arrhythmia in selected patients. PMID- 2917387 TI - Coronary dilation with standard dose dipyridamole and dipyridamole combined with handgrip. AB - Intravenous dipyridamole is widely used to produce coronary vasodilation during cardiac imaging procedures. However, the routinely used dose of dipyridamole (0.56 mg/kg IV over 4 min) does not always result in maximal coronary dilation. The addition of isometric handgrip during dipyridamole coronary dilation has been reported to substantially increase coronary blood flow over dipyridamole alone. We compared the coronary vasodilation resulting from infusion of the standard dose of dipyridamole with that resulting from a maximally dilating dose of intracoronary papaverine in 12 patients with angiographically normal coronary arteries. We also assessed the effect on coronary blood flow velocity of the addition of isometric handgrip during dipyridamole coronary dilation. Changes in coronary blood flow velocity were measured with a 3F coronary Doppler catheter. The coronary flow reserve (peak/resting coronary flow velocity ratio) after dipyridamole (3.7 +/- 1.2 [mean +/- SD] was less than that seen after papaverine (4.4 +/- 0.5, p less than 0.05), and the coronary vascular resistance index during dipyridamole coronary vasodilation (0.28 +/- 0.09) was greater than during papaverine (0.22 +/- 0.03, p less than 0.05). The dipyridamole coronary flow reserve was less than 3.0 in four subjects and was 2.0 or less in two subjects. The addition of isometric handgrip to dipyridamole coronary vasodilation produced an 8% increase in mean heart rate and a 17% increase in mean arterial pressure, but coronary flow reserve was unchanged (3.8 +/- 1.1 before handgrip vs. 4.0 +/- 1.1 with handgrip). Quantitative angiography in six patients revealed no change in coronary caliber with the addition of handgrip.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2917388 TI - Follow-up of patients undergoing percutaneous mitral balloon valvotomy. Analysis of factors determining restenosis. AB - This study reports the clinical follow-up (13 +/- 1 months) of 100 consecutive patients who underwent percutaneous mitral balloon valvotomy (PMV). Echocardiographic (n = 32) and cardiac catheterization (n = 37) data from this group are also included. Patients were divided into two groups by an echocardiographic score. PMV resulted in a good hemodynamic result (post-PMV mitral valve area, greater than or equal to 1.5 cm2) in 88% of patients with a score of 8 or less and 44% of patients with a score of more than 8. Eighty-eight percent of patients with a score of 8 or less (n = 57) were New York Heart Association (NYHA) functional Classes III and IV before PMV; at follow-up, 81% were NYHA Class I and 12% were NYHA Class II. There were no deaths; three patients underwent mitral valve replacement (MVR). Ninety-eight percent of patients with a score of more than 8 (n = 43) were NYHA Classes III and IV before PMV; at follow-up, 58% were NYHA Classes I and II. Seven patients who did not improve and were not surgical candidates died 3.8 +/- 1.2 months after PMV. Nine patients who were surgical candidates underwent elective MVR at 4 +/- 0.9 months after PMV. Repeat cardiac catheterization demonstrated restenosis in only one of 27 patients (4%) with a score of 8 or less. Mitral valve area after PMV was 1.9 +/- 0.1 cm2 and at follow-up was 2 +/- 0.1 cm2 (NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2917389 TI - Hypertrophic cardiomyopathy in the elderly. Distinctions from the young based on cardiac shape. AB - The striking clinical and pathologic features of hypertrophic cardiomyopathy have been defined almost exclusively in the young. Little is known about this condition in the elderly, although it is assumed to be part of a single disease. Accordingly, we studied 28 patients who were 65 years of age and older (mean age, 72 +/- 6.4 years) who were diagnosed as having hypertrophic cardiomyopathy by M mode, two-dimensional, and Doppler echocardiography and compared them with a group of 28 consecutive patients with this disease who were younger than 40 years of age (mean age, 26 +/- 9.5 years). No clinically detectable differences existed between the two groups, except for an increased incidence of mild hypertension in the elderly. Echocardiography in both groups showed hypertrophy with a small left ventricular cavity, and Doppler outflow tract velocity or cardiac catheterization in most patients showed systolic anterior motion of the mitral valve or a systolic outflow tract gradient or both. Significant differences existed between both groups, however, concerning left ventricular size and shape. The elderly group had a predominantly ovoid cavity contour with normal septal curvature. In contrast, in the young group, a markedly abnormal cardiac shape predominated (p less than 0.0001) with a crescent-shaped left ventricular cavity and a reversed curvature of the interventricular septum. The right ventricular free wall was prominent by echocardiography in the young compared with the elderly group (p less than 0.001). Apart from a more frequent history of mild hypertension in the elderly, likely related to age, these findings show that hypertrophic cardiomyopathy, when present in the elderly, has similar clinical features to that in the young.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2917390 TI - Effect of magnesium on anginal attack induced by hyperventilation in patients with variant angina. AB - To examine whether or not magnesium suppresses coronary spasm, the effect of magnesium infusion on anginal attacks induced by hyperventilation was studied in 20 patients with variant angina. In all patients, anginal attacks associated with ischemic ST segment changes on the electrocardiogram were repeatedly induced by hyperventilation. The study was performed in the early morning successively for 3 days. On days 1 and 3 (control studies), 50 minutes before the hyperventilation test, a 5% glucose solution was infused as a placebo. On day 2 (magnesium study), 50 minutes before the hyperventilation test, magnesium sulfate (0.27 mM/kg body wt) was infused during a 20-minute period. During the control studies, anginal attack was induced by hyperventilation in all 20 patients, whereas during the magnesium study, anginal attack was induced by hyperventilation in only six (30%) of the 20 patients (p less than 0.001 vs. control studies). The changes in arterial blood pH and PCO2 caused by hyperventilation were not significant between the control study and the magnesium study. Mean serum magnesium concentration increased from 2.2 +/- 0.2 to 6.0 +/- 0.5 mg/dl immediately after infusing magnesium and was 4.5 +/- 0.6 mg/dl before the hyperventilation test during the magnesium study. We conclude that magnesium suppresses anginal attacks induced by hyperventilation in patients with variant angina. PMID- 2917391 TI - Quinidine-induced action potential prolongation, early afterdepolarizations, and triggered activity in canine Purkinje fibers. Effects of stimulation rate, potassium, and magnesium. AB - Early afterdepolarization (EAD)-induced triggered activity is thought to contribute to the cardiac arrhythmogenic effects of several class I antiarrhythmic agents. The combination of quinidine therapy, bradycardia, and hypokalemia is known to predispose to torsade de pointes, which is a form of atypical polymorphous ventricular tachycardia commonly associated with long QT intervals. Recent clinical reports have shown suppression of quinidine-induced torsade de pointes with intravenous administration of magnesium sulfate. To provide further understanding of these relations, we used standard microelectrode techniques to examine the time course of quinidine-induced action potential prolongation, EAD, and triggered activity development and the dependence of these changes on [K+]0, [Mg2+]0, and stimulation frequency in isolated Purkinje fiber preparations exposed to low concentrations of the drug. At slow stimulation rates, the quinidine-induced increase of action potential duration was slow to develop and failed to reach a steady state after 3 hours of exposure to the drug. EAD and EAD-induced triggered activity generally became apparent 70-90 minutes after adding the drug. Quinidine produced triggered activity in 10 of 22 preparations superfused with Tyrode's solution containing normal [K+]0 (3.5-4.0 mM) and in six other preparations when [K+]0 was reduced. In the presence of normal [K+]0, two types of EAD and triggered activity were distinguished. In four of 10 preparations, this activity arose from phase 2 of the action potential; in eight of 10, it was associated with phase 3; and in two experiments, both types were present in the same preparation. The incidence of both forms of triggered responses depended greatly on the rate of stimulation. Triggered activity arising from phase 3 was always manifest at rates considerably slower than those giving rise to phase 2 activity. Both forms of triggered activity were sensitive to changes in the extracellular concentration of potassium and magnesium. Lower-than normal levels of these electrolytes facilitated the manifestation of triggered activity, whereas elevated levels suppressed or caused a shift in the frequency dependence of the activity. Phase 2, but not phase 3, EADs were abolished in response to increased [Mg2+]0. The data show a clear congruity between the conditions that predispose to torsade de pointes in the clinic and the conditions under which quinidine may induce triggered activity and marked action potential prolongation in isolated Purkinje fibers.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2917392 TI - Effect of acute volume load on refractoriness and arrhythmia development in isolated, chronically infarcted canine hearts. AB - In normal isolated, perfused canine ventricles, increased ventricular volume leads to shortening of refractoriness. To test the hypothesis that myocardium within an infarction zone is more susceptible to volume-induced changes in refractoriness than is normal myocardium, we measured strength-interval curves at low and high end-diastolic volumes at control and infarcted sites in 14 isolated, blood perfused, canine hearts with chronic (greater than 25 days) infarctions. In addition, the effect of volume load on inducing ventricular arrhythmias was studied at one to six sites in 11 hearts. Differences in refractoriness and inducibility at low (22 +/- 5 ml) and high (48 +/- 6 ml) end-diastolic volumes were compared. At control sites, volume load reduced the absolute refractory period from 178 +/- 16.5 to 175 +/- 16.7 msec (p less than 0.05), but no significant change in the relative refractory period occurred. At infarcted sites, the change in refractoriness with volume load was greater, and the absolute refractory period decreased from 171.5 +/- 21 to 160.6 +/- 26.3 msec (p less than 0.01), and the relative refractory period decreased from 180.1 +/- 22.1 to 169.9 +/- 26 msec (p = 0.05). This differential effect of volume load on refractoriness led to an increased dispersion of overall refractoriness at high volume. Infarcted sites showing the largest changes in refractoriness were characterized by patchy scars extending at least to the midmyocardium, whereas sites located within areas of transmural scar, endocardial scar, or rare microfoci of fibrosis showed no increased sensitivity to volume load. Of eight hearts in which no tachyarrhythmias were inducible during programmed electrical stimulation at low volume, four had tachyarrhythmias induced at high volume. Sites of stimulation associated with a conversion from noninducible to inducible tachyarrhythmias showed a larger degree of shortening of refractoriness (change in absolute refractory period: 24.7 +/- 16.5 vs. 3.9 +/- 6.5 msec, p less than 0.05). These data indicate that volume loading may have electrophysiologic significance and that it may be of greater functional importance under pathologic conditions. PMID- 2917394 TI - Homogeneity out of heterogeneity. PMID- 2917393 TI - Effect of early and advanced atherosclerosis on vascular responses to serotonin, thromboxane A2, and ADP. AB - In monkeys with early and advanced atherosclerosis, we examined responses to the three major vasoactive agonists that are released when platelets aggregate. Measurements were obtained in normal cynomolgus monkeys and in monkeys fed an atherogenic diet for 4 +/- 1, 9 +/- 1, and 19 +/- 1 months (mean +/- SEM). Morphometry of femoral and iliac arteries indicated that 4 months of atherogenic diet produced only slight intimal thickening, 9 months produced early lesions, and 19 months produced approximately 5-10 fold greater intimal proliferation than did 9 months of atherogenic diet. Serotonin and adenosine 5'-diphosphate (ADP), which are endothelium-dependent agonists, and adenosine and phenylephrine, which are endothelium-independent agonists, were injected intra-arterially into the perfused hind limb. Thromboxane A2 analogue U46619 also was studied. Vasoconstrictor responses to serotonin were potentiated, and vasodilator responses to ADP were impaired by early and advanced atherosclerosis. In contrast, vasoconstrictor responses to phenylephrine and vasodilator responses to adenosine were similar in all groups. Vasoconstrictor responses to U46619 were potentiated by advanced atherosclerosis. Thus, vascular responses to serotonin, ADP, and thromboxane A2 are altered by atherosclerosis in a direction that would favor vasoconstriction when platelets aggregate. Furthermore, because responses to endothelium-dependent agonists are altered, these data suggest that endothelium is dysfunctional in early atherosclerosis. These findings may explain, in part, the propensity for exaggerated vasoconstriction even in arteries with minimal atherosclerotic lesions. PMID- 2917395 TI - The ongoing natural experiment of cardiovascular diseases in Japan. PMID- 2917396 TI - Office evaluation of hypertension. A statement for health professionals by a writing group of the Council for High Blood Pressure Research, American Heart Association. AB - The ultimate purpose of office evaluation of the hypertensive patient is to provide optimal management of blood pressure and associated risk factors. The workup includes a valid estimate of average blood pressure, including home blood pressure measurements, assessment of the degree of target organ damage, and identification of other risk factors, including family history. The history and physical examination should be directed to the principal target organs, including the optic fundi, central nervous system, heart, and kidneys. Laboratory evaluation should include urinalysis, ECG, and determinations of blood hemoglobin/hematocrit, creatinine, potassium, glucose, and cholesterol, including HDL fraction. This information will alert the physician to the possibility of curable forms of hypertension such as coarctation of the aorta, pheochromocytoma, primary aldosteronism, and renovascular hypertension. The office evaluation is also concerned with estimating prognosis and extent of organic damage, which is essential in planning management. The nurse or trained allied health professional should be used to the fullest possible extent both in evaluation and management of hypertensive patients. PMID- 2917398 TI - Should we recommend contact lenses? PMID- 2917397 TI - Patterns of lens care practices and lens product contamination in contact lens associated microbial keratitis. AB - A prospective study of 24 contact lens patients with culture- or histopathology proven microbial keratitis was performed between July and December 1987 to determine associated lens care practices and patterns of lens care product contamination. A questionnaire was used to document methods of lens care. Bacterial cultures were performed on all available contact lenses, lens cases, and solutions (including saline, disinfectant, daily cleaner and wetting agents), in addition to standard smears and cultures of the corneal ulcer. Failure to follow standard recommendations regarding contact lens care was widespread (21 of 24, 88%). In the majority of patients (20 of 24, 83%) bacterial contamination of the contact lens, case, and/or solutions was present. Almost two-thirds (15 of 24, 62%) of patients used solutions that were more than 3 months old. Cosmetic extended wear lens patients were most likely (7 of 8, 88%) to use solutions that were more than 3 months old and very likely (6 of 8, 85%) to have contaminated solutions. Efforts to improve lens care and decrease lens product contamination are necessary to prevent contact lens associated corneal ulcers. PMID- 2917399 TI - Opti-Free chemical disinfectant: a safety study with various soft contact lenses. AB - A 6-month, Phase I clinical study evaluated Opti-Free, a new polyquaternium-1 chemical disinfectant intended for use with all types of soft contact lenses. Fifty-one patients were enrolled and divided into two groups. Group A used the product under exaggerated conditions, with daily exposure of Durasoft 3 (55%) and Hydrocurve II (55%) medium water content, ionic lenses to 5 mL of Opti-Free for 16 hours. Beginning on day 15, group A patients began a normal daily use schedule. Patients in group B wore CSI (38%), Permalens (71%), and Softcon (55%) contact lenses and used the regimen under normal daily use conditions throughout the study. The result indicate that Opti-Free is safe and effective under both normal and exaggerated use conditions. The implications of these data for patient safety are discussed. PMID- 2917400 TI - Fluoroperm extended wear RGP contact lenses for myopia, hyperopia, aphakia, astigmatism, and keratoconus. AB - One hundred fifteen eyes of 62 patients were fit with paflufocon-A (Fluoroperm) rigid gas permeable (RGP) contact lenses. Patients included myopes, hyperopes, aphakes, and keratoconic and astigmatic patients; the latter patients were fit with bitoric designs for large amounts of corneal astigmatism or front toric designs for residual astigmatism. Thirty of the 52 patients (58%) who completed the study were able to wear the lenses continuously without complications; six (12%) were able to achieve extended wear for up to one month. The average visual acuity across the study was 20/20. Three complications were observed, resulting in a complication rate of 6%. PMID- 2917401 TI - Immune responses in monkeys to lenses from patients with contact lens induced giant papillary conjunctivitis. AB - The clinicopathologic findings in contact lens-induced giant papillary conjunctivitis (GPC) suggest that the syndrome is the result of a complex immunological process, an idea supported by the presence of elevated tear concentrations of IgG and IgE in GPC. Several groups of investigators have proposed that GPC may be due, in part, to the coating of the contact lens. To test this hypothesis we undertook development of an animal model of GPC in cynomolgus monkeys. Two soft contact lenses from patients with GPC, two from asymptomatic contact lens wearers, and two clean, unused lenses were each placed in one eye and held in place with a partial tarsorrhaphy. Tears from the two monkeys with GPC lenses showed increased levels of IgG (43 +/- 10 micrograms/mL), IgA (54.3 +/- 12.8 micrograms/mL) and IgE (7.7 +/- 3.3 IU/mL) 35-75 days post lens placement. While the tears from the two monkeys with clean lenses, and the two monkeys with lenses from asymptomatic contact lens wearers had elevated levels of IgG compared to the contralateral control eye without a lens, the tear IgE levels remained normal. Histopathology studies of tarsal conjunctival biopsy material from the monkeys with GPC lenses showed an intense round cell infiltrate at the epithelial-stromal junction. Mast cells were seen in the epithelial layers. These studies suggest that some factor (or factors) in the lens coating from GPC patients was able to induce a local tear IgE response and histopathological changes in monkeys. These changes are similar to the histopathological and immunological findings in human patients with GPC. PMID- 2917402 TI - Traumatic cataract management in penetrating ocular injury. AB - Eight patients with lens damage caused by penetrating ocular trauma underwent delayed cataract removal four to 30 days after the initial injury. All but one patient, who had a retinal detachment, achieved a visual acuity of 20/50 or better. A short delay in the treatment of the cataract as well as the use of intraocular lenses did not appear to have an adverse effect on the visual prognosis. PMID- 2917403 TI - Index of refraction. PMID- 2917404 TI - Corneal endothelial changes associated with contact lens wear. AB - Contact lenses may induce short- and long-term corneal endothelial changes. The endothelial bleb response is a short-term, reversible change noted with contact lens wear. Long-term endothelial changes such as polymegethism (increased variation in cell size) and pleomorphism (a decrease in the frequency of hexagonal cells) have also been detected in polymethylmethacrylate, rigid gas permeable, and daily and extended wear soft contact lens patients. These morphometric changes have also been seen in myopes, aphakes, and corneal transplant recipients. Differences in endothelial morphometry between the central and mid-peripheral regions of the cornea have also been noted in hard lens wearers. The long-term significance of these findings is discussed. PMID- 2917405 TI - Somatotopically organized transient projections from the primary somatosensory cortex to the cerebellar cortex. AB - The organization of transient projections from the primary somatosensory cortex (S-I) to the cerebellar cortex in neonatal kittens was examined using orthograde intraaxonal labeling techniques. Tritiated amino acid injections into face, forelimb and hindlimb areas of representation in S-I labeled mossy fiber-like terminals of cerebrocerebellar axons in different areas of the cerebellar cortex bilaterally. The hindlimb area of S-I projected to lobules I-IV in the anterior lobe and to ventral folia of the paramedian lobule (PML). Injections into forelimb areas of S-I labeled terminals in lobules IV and V and in intermediate and dorsal folia of the PML. The face area of S-I projected to the lobules V and VI, to medial folia in the ansiform and simplex lobules and to dorsal PML folia. Labeled terminals were more numerous in the cerebellar cortex contralateral to the S-I injections, except in lobules I and II and the ventral PML where the density of hindlimb input was approximately the same on both sides. These observations were supplemented by findings that small wheat germ agglutinin horseradish peroxidase (WGA-HRP) injections into the dorsal or ventral PML resulted in retrogradely labeled layer V pyramidal neurons in lateral (face and forelimb) and medial (hindlimb) areas of S-I respectively. The somatotopic organization of transient S-I cerebrocerebellar projections is very similar to the topography of cerebellar somatosensory afferent pathways in adult cats. PMID- 2917406 TI - Lipid peroxidation in developing fetal guinea pig brain during normoxia and hypoxia. AB - Lipid peroxidation in the fetal guinea pig brain was studied at 30, 35, 40, 45, 50, and 60 days of gestation. Conjugated dienes and fluorescent compounds, indices of lipid peroxidation, peaked at 35 days of gestation, decreased by 45 days, and remained at that level until birth. The higher levels of peroxidation products in early gestational periods (30-40 days) suggest that either the anti oxidant mechanisms for scavenging oxygen free-radicals and further metabolizing oxidation products are underdeveloped, or the rate of peroxidation is higher than periods near term. Prenatal hypoxia increased the levels of conjugated dienes and fluorescent products in the brains of preterm (50 days) and term (60 days) fetuses. Brain homogenates incubated in air at 37 degrees C underwent rapid lipid peroxidation as measured by the level of thiobarbituric acid (TBA)-reactive substances. However, term brain showed a higher rate of peroxidation and attained higher steady state levels of TBA-reactive substances than preterm brain. This may be due to the higher levels and degrees of unsaturation in fatty acids in term brain. Following hypoxia, term brain showed 5 times the rate of lipid peroxidation and a 3-fold increase in total TBA-reactive substances over controls. These studies show that a significant degree of lipid peroxidation is occurring in the fetal brain during gestation and that the developing brain is more susceptible to lipid peroxidation near term. Furthermore, prenatal hypoxic stress further increases the susceptibility of the brain to peroxidative reactions. PMID- 2917407 TI - Regulation of granule cell number by a predetermined number of Purkinje cells in development. AB - Development dysgenesis of Purkinje cells or granule cells was analyzed for the reciprocal effect of reduced number of each cell type on the other. A single pre- or postnatal injection of methylazoxymethanol acetate (MAM) in the rat reduces either the number of Purkinje cells or the number of granule cells when administered at the time of their respective genesis. The total number of these two types of neurons was obtained from cell density values of each layer and the total volume of the granular layer and the area of the Purkinje cell layer. The results show that Purkinje cells (targets) strictly determine the maximum number of granule cells (afferent neurons) following deficits in the number of Purkinje cells produced by prenatal MAM administration. Deficits in Purkinje cells were accompanied by a proportionally smaller number of granule cells so that the ratio remained constant. On the other hand, the reduction in the number of granule cells of the postnatal MAM model did not affect the number of Purkinje cells. These results indicate that the maximum number of these afferent neurons is constrained unidirectionally through a property defined by the number of their target neurons which develop earlier. Furthermore the number of afferent cells had no effect on the number of target cells. PMID- 2917408 TI - Peripheral competition in the control of sensory neuron numbers in Xenopus frogs reared with a single bilaterally innervated hindlimb. AB - Sensory neurons were counted in the hind-limb innervating spinal ganglia on both sides of juvenile Xenopus frogs which, as tadpoles, had had one hind limb bud amputated prior to innervation, and a channel made to allow innervation of the remaining limb bud from both sides. The total number of sensory neurons surviving on the two sides approximated the number on one side of normal frogs, the ipsilateral and contralateral numbers being negatively correlated. These effects differ markedly from the effects on motoneuron numbers, suggesting different control mechanisms of cell death in the two neuronal classes. PMID- 2917409 TI - Spatial arrangement of radial glia and ingrowing retinal axons in the chick optic tectum during development. AB - Neuroanatomical tracing of retinal axons and axonal terminals with the fluorescent dye, DiI, was combined with immunohistochemical characterization of radial glial cells in the developing chick retinotectal system. Emphasis was placed on the mode of the tectal innervation by individual retinal axons and on the distribution and fate of the tectal radial glial cells and their spatial relation to retinal axons. It was obvious from fluorescent images obtained from anterogradely filled axons that these axons deserted the superficial stratum opticum (SO) to penetrate the stratum griseum et fibrosum superficiale (SGFS) by making right-angled turns within the SO. Frequently, axons which had invaded the SGFS were bifurcated and had a superficial branch which remained within the SO. Terminal axonal arborization occurred at various depths within the SGFS. Characterization of the tectal glial cells and their radial fibers by means of the anti-filament antibody, R5, and post-mortem staining with the fluorescent dye, DiI, revealed the following. (a) At least from day E8 to P1, tectal glial fibers traversed all tectal layers from the periventricular location of their somata to the superficial interface between SO and pia mater. In this interface they enlarged and formed characteristic endfeet. (b) Glial endfeet covered the whole tectal surface. They showed at early ages anterior-posterior differences having a higher density in the posterior tectum. These differences disappeared at embryonic day E13. (c) After innervation, glial endfeet of the anterior tectal third were arranged in rows parallel to the retinal fibers within the SO. This arrangement was not observed in eyeless embryos. (d) Radial glial fibers could be stained with R5 from day E8 to late embryonic stages throughout their entire length. (e) At the first posthatching days, only the segments of the radial glial fibers restricted to the thickness of the SO were R5-positive, although the fibers still traversed throughout the depth of the tectum. The results are discussed in context to the genesis of the retinotectal projection. PMID- 2917410 TI - The postnatal development of layer VI pyramidal neurons in the cat's striate cortex, as visualized by intracellular Lucifer yellow injections in aldehyde fixed tissue. AB - The postnatal development of layer VI pyramidal neurons in the cat's striate cortex has been studied by means of intracellular injections of Lucifer yellow in aldehyde-fixed tissue (LYF technique). It is shown that the LYF technique gives results qualitatively and quantitatively similar to results obtained with other techniques (Golgi, marker-injections in viable tissue). Quantitative analysis demonstrated significant increases in soma diameter, number and length of basal dendrites, length of second order apical dendrites and, in particular, in number of spines/unit dendritic length, during the first postnatal month. Maturation of the basal dendritic tree and increase in number of spines continue in the second postnatal month. At later postnatal times soma diameter and number of spines decrease by about 20%. Dendritic varicosities are most frequent during the first postnatal week, and decrease in number steadily from thereon. The late maturation of layer VI pyramidal neurons suggests that these cells might be affected by early peripheral lesions and/or sensory deprivation to which the striate cortex of the cat has been shown to be most susceptible around the end of the first postnatal month. PMID- 2917411 TI - Morphologic plasticity of rapid-onset neurites in NG108-15 cells stimulated by substratum-bound laminin. AB - Undifferentiated NG108-15 cells, when replated onto laminin-coated substrata, extend multipolar, highly branched neurite-like extensions up to 200 microns in length within 4 h; morphologic and pharmacologic properties of these 'rapid-onset neurites' have been described recently. The present study has extended these observations, using time lapse video recordings of their dynamic behavior and additional pharmacologic studies. Rapid-onset neurites and neuronal growth cones were shown to be regulated in an identical manner in all respects examined, including inhibition of outgrowth by cytochalasin B. Of particular interest was the observation that rapid-onset neurites in contact with laminin exhibited an extremely high rate of turnover, which was inhibited by 5'-deoxy-5' methylthioadenosine (MTA). This system provides a uniquely favorable in vitro preparation in which neuritic plasticity can be elicited, directly observed and experimentally modulated under controlled conditions. PMID- 2917412 TI - Analysis of slow-onset neurite formation in NG108-15 cells: implications for a unified model of neurite elongation. AB - When undifferentiated NG108-15 cells are plated onto polylysine coated Petri dishes in serum-free medium, they form neurites within 1-4 h if plated in the presence of laminin or 5'-deoxy-5'-methylthioadenosine (rapid-onset neurites). In the absence of such agents, serum-deprived NG108-15 cells extend axon-like neurites onto polylysine over several days; here we characterize the dynamic behavior of this slow-onset outgrowth pattern in detail. Individual cells plated on laminin expressed a gradual multipolar-to-unipolar transition due to rapid onset neurites becoming remodelled into the appearance of slow-onset neurites. This phenomenon reflected the selective stabilization of certain rapid-onset neurites, along with the restriction of motility to their distal tips. Based upon the properties and interactions of both rapid- and slow-onset neurites in NG108 15 cells, a unified model for neurite formation is presented. PMID- 2917413 TI - Altered cell shapes in fibroblasts treated with 5'-deoxy-5'-methylthioadenosine: relation to morphogenesis of neural cells. AB - In the present study, mouse 3T3 fibroblasts and primary human foreskin fibroblasts exposed to MTA (5'-deoxy-5'-methylthioadenosine) were found to achieve neural-like cell shapes and to extend long, multipolar processes rapidly and reversibly. Time lapse recordings and pharmacologic studies revealed that process formation in MTA-treated fibroblasts was mechanistically related to the rapid-onset mode of neurite formation previously characterized in neural hybrid NG108-15 cells. These data, together with evidence presented elsewhere, indicate that MTA selectively reorganizes the mode of expression of a specific cytoplasmic machinery that is active in many types of cells, and which is involved in regulating cell shape and neurite formation in developing neurons. PMID- 2917414 TI - Longitudinal changes in cranial base angulation in mandibulofacial dysostosis. AB - Longitudinal measures of cranial base angulation (nasion-sella-basion angle; N-S Ba) were obtained in 24 patients with mandibulofacial dysostosis (MFD), with records available over time spans ranging from 2 years to 29 years. Initial measurements, obtained at ages ranging from 1 month to 13 years, 6 months, indicated basilar kyphosis (N-S-Ba less than 120 degrees) in five patients. Twenty-one patients showed increasing flexure of the cranial base angle (CBA) over time, eight to such a degree that their initially normal CBAs eventually fell into the kyphotic range. At the time of the final available records (age range 4 years, 0 months to 29 years, 2 months), a total of 54 percent of patients thus fell into the kyphotic range. These results point to the time-dependent nature of the appearance of abnormal CB angulation in some patients. In addition, there was a predominance of males in those patients showing significant change in cranial base angulation over time. PMID- 2917415 TI - Odontometrics of the permanent teeth in cleft lip and palate: systemic size reduction and amplified asymmetry. AB - Mesiodistal diameters of the permanent teeth of 70 isolated cleft lip and palate cases were analyzed. Subjects with unilateral cleft lip and palate (CLP) exhibit significantly smaller crown sizes than controls. Size reduction averages 2.3 percent, which translates to a 5.2-mm mean difference summed across all 28 permanent teeth. Bilateral cases are twice as affected, with a 4.2 percent reduction (9.3 mm). The baseline level of left-right asymmetry is significantly amplified across the whole dentition, encompassing both early- and late-forming teeth and constituting a 30-percent increase in overall asymmetry. Also, there is a localized peak of disproportionately high asymmetry centered on the upper lateral incisor but extending to both the central incisor and canine. The consistency of these differences across all tooth types and among early- and late forming teeth implies that isolated CLP is a sequelae of a systemic, generalized restriction of these individuals' growth potential. PMID- 2917416 TI - Screening of velopharyngeal inadequacy by differential pressure measurements. AB - Warren (1979) described an approach for screening velopharyngeal inadequacy using a device (PERCI) that measures orifice differential pressure (P). The PERCI score is based on the relationship between velopharyngeal orifice (VPO) area and velopharyngeal orifice differential pressure. The purpose of this study was to test the original assumptions, which were based on modeling experiments and a small sample size. The sample in this study included 515 subjects who demonstrated various degrees of velopharyngeal inadequacy. The pressure-flow technique was used to estimate velopharyngeal orifice size and to measure orifice differential pressure. The data demonstrate that differential pressures greater than 3.0 cm H2O generally predict adequacy of closure, whereas differential pressures less than 3.0 cm H2O usually indicate inadequacy. These findings support the use of orifice differential pressure as a simple screening of velopharyngeal function. PMID- 2917418 TI - Changes in articulation and resonance after tongue flap closure of palatal fistulas: case reports. AB - This paper describes speech changes in three patients after tongue flap closure of various sized palatal fistulas. In all three patients articulation and lingual mobility appeared to be unaffected by excision of tongue tissue for the procedure. However, a large protruding tongue flap was noted to interfere with the articulation of sibilants in one patient. All patients showed a reduction in overall hypernasal resonance and nasal emission, although one patient developed nasal turbulence postoperatively and another required a pharyngeal flap for total elimination of hypernasality. This paper points out the need for a systematic investigation into the effects of this surgery on speech. PMID- 2917417 TI - Intravelar veloplasty: a prospective study. AB - Preliminary results are reported from a prospective, alternated, single institution study of the effect of intravelar veloplasty (IVV) upon postpalatoplasty velopharyngeal incompetence. Two senior surgeons standardized their operative procedures and then performed or directly supervised all surgery. Patients alternately had palatoplasty with or without IVV. One speech pathologist conducted all perceptual speech and language evaluations without knowledge of the surgical procedure when the children were 3 years of age. The IVV and non-IVV groups were similar with respect to cleft anatomy, mean age at palatoplasty, and audiograms at 1 and 3 years of age. The findings from a sample of 51 patients were that surgical retropositioning and approximation of the levator muscles during initial palatoplasty (1) did not demonstrably affect the incidence of postpalatoplasty auditory perceptual symptoms of velopharyngeal incompetence; (2) required a significantly longer operating time; (3) were costlier than the control procedure; and (4) did not have greater morbidity than the control procedure. These findings suggest either that there is no beneficial effect of IVV upon postpalatoplasty velopharyngeal competence or that the effect, if present, is of small magnitude. PMID- 2917419 TI - The role of pressure flow and endoscopic assessment in successful palatal obturator revision. AB - The purpose of this paper is to illustrate the value of combined aerodynamic and endoscopic examination of velopharyngeal function in the revision of prosthetic speech appliances. Use of these combined measures enables the clinician to identify accurately the site(s) of any under- or overobturation. Furthermore, any needed revision is completed accurately and efficiently. PMID- 2917420 TI - Patterns and location of velopharyngeal valving problems: atypical findings on video nasopharyngoscopy. AB - Patterns of velopharyngeal (VP) valving and the location of velopharyngeal gaps were investigated in 246 consecutive nasopharyngoscopy studies. The predominant pattern of closure was coronal (68 percent), followed by the circular (23 percent), circular with a Passavant's ridge (5 percent), and sagittal (4 percent) patterns. Gaps were found in 181 patients; in 121 they were considered typical (centrally located), in 28 they were in one of the lateral aspects of the valve, and in 32 they were attributed to the shape of the adenoid tissue or to abnormalities in the anatomy or function of the posterior border of the soft palate. Atypical findings occurred primarily in patients with a coronal pattern of valving. These findings raise further questions about treatment for patients with atypical valving problems. PMID- 2917421 TI - Dimensions of the cleft nasal airway in adults: a comparison with subjects without cleft. AB - The prevalence of mouthbreathing among individuals with cleft lip and palate is significantly higher than in the normal population. This has been attributed to nasal deformities that tend to reduce nasal airway size. The purpose of the present study was to determine how a heterogeneous adult group with cleft lip and palate differs in terms of nasal airway cross-sectional area from an adult group without cleft during the inspiratory and expiratory phases of breathing. The pressure-flow technique was used to estimate nasal airway size in 15 adults without cleft (15 years or older) and 37 adults with cleft lip, cleft palate, or both. Mean areas and standard deviations for subjects without cleft were 0.63 cm2 +/- 0.17 during inspiration and 0.56 cm2 +/- 0.14 during expiration. This difference is statistically significant (p less than 0.01). Mean areas and standard deviations for all subjects with cleft were 0.37 cm2 +/- 0.18 during inspiration and 0.40 cm2 +/- 0.20 during expiration. This difference is not statistically significant (p greater than 0.15). Twenty-two of the subjects with cleft had nasal areas considered to be impaired (below 0.40 cm2) as compared with only three of the subjects without cleft. A two factor analysis of variance (ANOVA) demonstrated that area changes during respiration are different for subjects with and without cleft (p less than 0.005), and that cleft nasal areas are smaller than noncleft areas for both phases of breathing (p less than 0.001). Inspiratory-expiratory differences between subjects with and without cleft are probably the result of developmental defects, reparative surgery or both.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2917422 TI - Specific binding to methylated polynucleotides in monoclonal anti-poly(dT) antibodies from autoimmune mice. AB - Six monoclonal antibodies (mAbs) reactive to synthetic polynucleotide, poly(dT), were established from spontaneous autoimmune MRL/MpJ-lpr/lpr mice and male BXSB mice by spleen cell hybridization method, and were analyzed for cross-reactivity with polydeoxy-5-methylcytidylic acid [poly(dmC)] in comparison with its unmethylated counterpart poly(dC). By direct binding tests, these mAbs, all of which had preponderant binding activity to poly(dT) relative to poly(dU), were divided into two groups: (i) four mAbs showing reactivity to poly(dmC) as well as to natural DNA preparations and (ii) two mAbs with limited reactivity to poly(dT) but no binding to poly(dmC) or natural DNAs. Inhibition binding tests with these synthetic polynucleotides demonstrated that one mAb (TP-A9) in the first group reacted specifically to poly(dmC), as well as to poly(dT). In the second group, one mAb (TP-B5) showed highly specific reactivity to poly(dT) that could not be inhibited by poly(dU), poly(dC), or poly(dmC). However, another mAb (TP-C8) in the second group showed reactivity to poly(dT) that could be inhibited by poly(dU) as well as by poly(dT). Thus, these findings indicate that monoclonal anti-poly(dT) antibodies can cross-react with poly(dmC) with different specificities and suggest that the methylated base may be one of the major antigenic sites of DNA molecules recognized by anti-DNA antibodies spontaneously produced in autoimmune mice. PMID- 2917423 TI - Serum terminal complement component levels in hypocomplementemic glomerulonephritides. AB - Measurements of serum C3 through C9 are reported for patients with acute poststreptococcal glomerulonephritis (AGN), membranoproliferative glomerulonephritis type I (MPGN I), MPGN II, and MPGN III. Except in MPGN II, depressed C5 levels correlated with depressed C3 levels. In MPGN II, levels of C5 and of other terminal components were normal. In MPGN III, markedly depressed levels of C7 through C9 correlated strongly with depressed levels of C3 and C5. C6 was less severely depressed. In MPGN I, terminal component levels were less often depressed than in MPGN III and in AGN, depression of terminal components was seen only when levels of C3 and C5 were extremely low. The data indicate that late terminal components are activated in MPGN III to a greater extent than in the other nephritides despite C5 activation approximately equal in extent to that in AGN and MPGN I. PMID- 2917424 TI - A properdin dependent nephritic factor slowly activating C3, C5, and C9 in membranoproliferative glomerulonephritis, types I and III. AB - The IgG fraction of serum from patients with membranoproliferative glomerulonephritis (MPGN) types I and III was found to contain a nephritic factor (NFI/III) which differed from that usually present in MPGN type II and partial lipodystrophy (NFII) in that it converts C5 and C9 as well as C3, is dependent on properdin for its activity, and requires an incubation period of several hours rather than 30 min for its demonstration. C3 conversion occurred in the absence of an intact classical pathway. This nephritic factor was found in patients with reduced serum levels of terminal components and its activity, like that of the nephritic factor in MPGN type II, correlated with the serum C3 level indicating that these nephritic factors play a large role in producing hypocomplementemia. Although potentially nephritogenic because of its ability to activate the terminal pathway, the presence of this nephritic factor did not clearly correlate with clinical course. PMID- 2917425 TI - Secretion of the terminal complement proteins, C5-C9, by human platelets. AB - The terminal complement components, C8 and C9, and to a lesser extent C5, C6, and C7, but minimal amounts of C3, were shown to be associated with washed human platelets. In unactivated platelets, the complement components were detected in the platelet pellet by hemolytic assays after centrifugation and disruption of the platelets by freeze-thawing. However, after platelets had been activated by collagen, thrombin, or aggregated IgG to induce aggregation, the complement components were released into the supernatant. The rank order of hemolytic activity of C9, C8, C7, C6, and C5 detected in the supernatants of activated platelets was quite different from that found in serum from the same donors, in the same assays. In particular, the serum C7 hemolytic titer was more than twice the serum C9 hemolytic titer, whereas the activity of C9 detected from platelets was more than twice that of C7. This argues against a purely nonspecific uptake of these proteins by platelets from plasma. The functional role of terminal complement components released from platelets during activation is unknown, but it is tempting to speculate that these proteins may have a role in platelet dependent immunological tissue injury. Because the C5b-9 membrane attack complex activates platelets, it is possible that release of terminal complement proteins serves to amplify platelet activation and may also play a role in diseases in which complement membrane attack complexes have been implicated. PMID- 2917426 TI - Inability of oral bovine transfer factor to eradicate cryptosporidial infection in a patient with congenital dysgammaglobulinemia. AB - A 31-year-old man with dysgammaglobulinemia Type I (deficient IgG, IgA, and elevated IgM) and persistent cryptosporidiosis was treated over a 13-week period with oral bovine transfer factor from calves immunized with cryptosporidia. Spiramycin was added toward the end of the treatment period. This patient failed to show clinical response although there was a decrease in the stool oocyst count from the value just prior to therapy. Bovine transfer factor alone and in combination with spiramycin failed to eradicate the infection in this man with well-documented stable cryptosporidiosis. PMID- 2917427 TI - The efficacy of intraoperative autologous transfusion in major shoulder surgery. AB - Perioperative blood loss associated with 36 cases of major shoulder surgery in which an intraoperative autologous transfusion device was used was compared with a control group of 36 shoulder surgery patients to determine the effectiveness of intraoperative autologous transfusion (IAT). Total blood loss in this retrospective review was evaluated by assessing the volume of transfused banked blood and the change in hematocrit. All surgical cases were performed by the same surgeon. The procedures considered in the study were humeral head and total shoulder replacement. Use of an intraoperative autotransfusion device was associated with fewer units of transfused banked blood and similar or smaller drops in hematocrit. While shoulder surgery can involve substantial blood loss, the authors recommend intraoperative autologous transfusion for revision of failed shoulder surgery, arthrodesis, joint replacement, or repairs of massive cuff tears when mobilization and tendon transfers are anticipated. The risk of disease transmission through banked blood, especially of acquired immune deficiency syndrome (AIDS) and hepatitis viruses, has increased the need for a heightened awareness and use of alternative blood sources such as IAT. PMID- 2917428 TI - Anterolateral compression fracture of the thoracolumbar spine. A seat belt injury. AB - A thoracolumbar injury is reported in four patients who were involved in motor vehicle accidents while wearing shoulder-lap belt assemblies. These injuries consisted of anterolateral wedge compression of a thoracolumbar vertebra with lateral compression occurring on the side opposite the restrained shoulder. The posterior elements were disrupted contralateral to the anterolateral body compression. There was no translation in any of these fractures, and there were no neurological injuries. All fractures united without significant late disability. Although there was no gross clinical instability in these fractures, two of the three columns of the spine are disrupted, suggesting potential instability. The postulated mechanism of injury, referred to as the roll-out phenomenon, is flexion and rotation about the axis of the shoulder strap. PMID- 2917429 TI - Back shape in brace treatment of idiopathic scoliosis. AB - This preliminary study has shown that bracing may improve the cosmetic appearance of a scoliotic back although the underlying curve remains unchanged. Thirty-two patients treated with the Boston brace for adolescent idiopathic scoliosis were assessed both roentgenographically and by integrated shape imaging system scanning before and after treatment. The mean follow-up time was 16 months. Surface shape improved in 41% of the patients, whereas roentgenographic improvement occurred in only 9%. Roentgenographic measurements should, therefore, be considered in conjunction with corresponding surface shape measurements in the assessment of brace treatment of scoliosis. PMID- 2917430 TI - Osteoporosis and heredity. AB - A retrospective epidemiological study was performed to determine whether postmenopausal osteoporosis is a hereditary condition. Frequency of fractures was calculated in women whose mothers had suffered vertebral fractures after a low energy trauma three decades earlier. The frequency of fractures was compared to the frequency in an age-matched control group. The daughters of the osteoporotic women were not more prone to sustain fractures than the controls. PMID- 2917431 TI - The use of a flexor carpi ulnaris muscle flap in the treatment of an infected nonunion of the proximal ulna. A case report. AB - Multiple efforts had failed to heal an infected nonunion of the proximal ulna. A flexor carpi ulnaris muscle pedicle flap was used to improve blood supply and soft-tissue coverage at the nonunion site. The muscle flap and application of the principles of nonunion treatment promoted bone healing and restoration of useful elbow function. PMID- 2917432 TI - Conventional cemented total hip arthroplasty. Assessment of clinical factors associated with revision for mechanical failure. AB - This study investigates risk factors associated with mechanical loosening of cemented total hip arthroplasties. Mechanical failure was evaluated using survivorship analysis on all arthroplasties performed at the authors' institution by the Orthopedic Service from March 1971 until September 1983. Failure was defined as the necessity for replacement of one or more components for any reason other than infection. The failure rate was approximately 1.7% per year and, at 12 years, 20% of the hips had failed. Variables evaluated as potential risk factors for arthroplasty revision included weight, gender, age, surgeon, preoperative functional status, prosthetic type, and diagnosis. A Cox proportional hazard analysis indicated that weight (p less than 0.015) and age (p = 0.087) are important determinants of hip failure. The use of regression trees identified subsets of patients at differing risks for failure. Patients who weighed less than 75.22 kg had the best outcome with a 90% survival to 12 years. Patients weighing more than 75.22 kg are at varying risk depending on their age. These data define a subset of special-risk patients not previously described. Patients weighing more than 75.22 kg who were older than 75.4 years had a revision rate of 73% by eight years. PMID- 2917433 TI - Roentgenographic changes in proximal femoral dimensions due to hip rotation. AB - Three human adult femurs were examined using anteroposterior (AP) roentgenograms in anatomical position and in 15 degrees, 30 degrees, and 45 degrees of internal and external rotation. Relatively small (15 degrees or less) amounts of femoral rotation can cause significant changes in proximal femoral dimensions on supine AP hip roentgenograms, and the magnitude of these changes increases with rotation. Fifteen degrees of rotation can change it by almost 3 mm. These changes are comparable to the medullary canal expansion of a normal adult femur over a five- to ten-year period. These changes in measured proximal femoral dimensions with rotation necessitate either an improved roentgenographic technique or precise rotational matching of standard supine roentgenograms to obtain accurate measurements of their changes over time. PMID- 2917434 TI - An examination of factors contributing to failure of bipolar prostheses. AB - Preoperative factors that may lead to poor results in bipolar prostheses were examined in 34 patients with aseptic failures of their prostheses. Nineteen cases were revised for acetabular pain, seven for failure of the bearing insert, seven for a loose stem, and one for dislocation. The single significant factor that predicted a poor outcome was the angle of the sourcil of the acetabular roof. The group with acetabular pain had an average sourcil angle of 15.6 degrees compared with 5 degrees in those that failed for other reasons. PMID- 2917435 TI - Progress in ankle arthroscopy. AB - Ankle arthroscopy is rapidly gaining in popularity as an important diagnostic and therapeutic procedure. Indications for this technique include pain, swelling, stiffness, instability, hemarthrosis, and locking of the ankle. The anteromedial, anterolateral, and posterolateral portals are most commonly used. The use of a short, 30 degrees oblique arthroscope, with an ankle holder and distractor, permits visualization of the entire joint. Operative treatment is facilitated by small joint shavers, burrs, knives, and baskets. Intraarticular problems such as chondromalacia, osteophytes, loose bodies, synovitis, osteoarthritis, fracture, and instability all can be addressed arthroscopically. Prior to this technique, the cause of chronic ankle pain was poorly understood. Now, lateral ankle impingement is a well-recognized entity that responds well to arthroscopic treatment. Ankle arthroscopy provides a safe, effective method of diagnosis and treatment with few complications. Further advances in equipment and technique should expand indications for this procedure. PMID- 2917436 TI - Wilson's osteotomy for the treatment of hallux valgus. AB - One hundred oblique distal first metatarsal osteotomies (Wilson's) were reviewed at an average of five years and two months following surgery. In 96 feet there was pain over the bunion or first metatarsophalangeal joint preoperatively. This pain was eliminated in 85 feet and improved in nine feet. Second metatarsalgia present preoperatively was relieved in five of seven feet, but 19 feet developed second metatarsalgia following surgery. The majority of patients were pleased with the outcome of the surgery. No significant complications were noted. The surgical technique of Wilson's first metatarsal osteotomy for hallux valgus is straight-forward and produces a predictably excellent result. PMID- 2917437 TI - Talonavicular dislocations and midfoot arthropathy in neuropathic diabetic feet. Natural course and principles of treatment. AB - Talonavicular dislocations, sometimes associated with other midtarsal arthropathy, occasionally occur in patients with diabetic neuropathy. The natural course and rationale of treating this diabetic arthropathy is presented, based on the literature and the authors' experience with eight cases. Appropriate management depends on the acuteness of the injury, the degree of deformity, and the degree of bone fragmentation. If the injury is acute and alignment is acceptable, immobilization and protective weight bearing may prevent progression of the neuropathic joint destruction. If dislocation is acute with marked deformity but there is little fragmentation and the foot has intact circulation, reduction and surgical arthrodesis may be indicated. If dislocation is chronic, with bone fragmentation and severe deformity, proper management consists of wearing custom-molded shoes with stiff rocker-bottom soles. Patellar tendon weight-bearing braces may be added if needed. For patients in this last category, surgical treatment is recommended as a last resort only if soft-tissue breakdown cannot be prevented by appropriate footwear and bracing alone. PMID- 2917438 TI - A scaphoid fracture associated with a displaced distal radial fracture in a child. AB - A hyperextension injury to the wrist caused a transverse scaphoid fracture associated with a displaced distal radial fracture in an 11-year-old boy. Anatomic reduction and immobilization in a long-arm cast for a period of 12 weeks resulted in subsequent healing of these fractures. The coexistence of a scaphoid fracture with a distal radius fracture in a child is important to recognize because reduction maneuvers are modified to effectively treat this combination of injuries. Patients with distal radial physeal injuries should be closely evaluated for clinical and roentgenographic signs of scaphoid fractures. PMID- 2917439 TI - Rotational stability of diaphyseal fractures of the radius and ulna fixed with Rush pins and/or fracture bracing. AB - The rotational stability of fractures of the radius and ulna treated with Rush pins and/or fracture bracing was studied in six fresh cadaver forearms. Forearm rotation and fracture site motion (rotation) were measured as functions of applied forearm torque and rotation (pronation-supination). Values were obtained from the forearm: (1) intact and with both bones fractured; (2) without fixation; (3) with a fracture brace; (4) with Rush pins; and (5) with a combination of Rush pins and a fracture brace. A brace was ineffectual in reducing fracture site motion when the wrist was rotated to specified angles compared to fracture site motion for the forearm with no fixation treatment rotated to the same angles. When loading to specific torque levels, however, the brace reduced fracture site motion to one-half the motion with no fixation treatment. Under both loading conditions, Rush pin fixation significantly and markedly reduced the fracture site motion (to approximately one-eighth of the motion with no fixation treatment), whereas a brace in conjunction with Rush pins did not significantly further reduce the fracture site motion. The radius showed more motion at fracture site than the ulna. PMID- 2917440 TI - Fracture interaction in the extremities, The possible relevance of posttraumatic osteopenia. AB - Regional osteopenia may persist after certain types of fractures. To investigate the practical importance of this observation, the authors studied 2744 past fractures in 1659 patients with present fractures. Radial fractures rarely occurred ipsilateral to previous radial fractures, whereas fractures of the hand were more often ipsilateral to previous hand fractures. Hip fractures rarely recurred in the same hips. Patients with previous cervical hip fractures, unlike those with previous trochanteric fractures, had a predominance of subsequent fractures distal to the hip ipsilaterally. Those with previous femoral shaft fractures were more likely to have subsequent fractures ipsilaterally. Both femoral shaft and patellar fractures were more often seen on the side of previous lower extremity fractures. Patients with previous tibial fractures had more subsequent fractures of the femur and tibia ipsilaterally, and their present tibial fractures were more frequently ipsilateral when these fracture types had occurred in the past. Some of these shifts from the equal distribution of fractures between the two sides may be due to posttraumatic osteopenia. PMID- 2917441 TI - Cytogenetic analyses on giant-cell tumors of bone. AB - Giant-cell bone tumors are considered to be benign proliferations composed of poorly differentiated mononuclear cells and large multinucleated giant cells with the appearance of osteoclasts. Treatment is usually surgical resection, but there is a small risk of local recurrence and metastasis. Cytogenetic analyses were performed on giant-cell bone tumors of six consecutive patients. Chromosomally abnormal clones were found in three of the tumors, but no two patients had the same chromosome abnormality. Thus, there was no correlation between any specific chromosome change and the clinical behavior or histology of giant-cell bone tumors. However, all of the tumors had a significantly higher incidence of nonclonal chromosome abnormalities than is encountered in cultures of normal cells. The most common nonclonal abnormalities involved unusual telomere-to telomere chromosome translocations. These findings suggest that the cells in these tumors are chromosomally unstable. The telomeres most frequently involved were on the long arm of chromosomes 19 and 20. PMID- 2917442 TI - Osteosarcoma in adults. One institution's experience. AB - Twenty-six patients were referred to the adult sarcoma clinic of the authors' institution between 1979 and 1986. The diagnosis was not confirmed in four patients. The median age of the 22 confirmed patients was 37. Twelve patients had central skeletal primaries; of these 12, seven had metastatic or unresectable disease. Six patients were treated with complete resection of tumor followed by adjuvant chemotherapy; of these six, four remained continuously disease-free at 25+, 29+, 72+, and 75+ months. Eight patients received no adjuvant chemotherapy following complete resection. Four have remained disease-free for more than two years (31, 33, 44, 44+ months); however, only one remains continuously disease free. Adults tolerated chemotherapy well and should be considered appropriate candidates for adjuvant trials. Many, however, will have advanced-stage, poor prognosis lesions and require alternative approaches for treatment. PMID- 2917443 TI - The displaced femoral neck fracture: internal fixation versus bipolar endoprosthesis. Results of a prospective, randomized comparison. PMID- 2917444 TI - Pylon fractures of the distal tibia. AB - Forty-two patients with pylon fractures were categorized into Ruedi and Allgower Type I (26%), Type II (29%), and Type III (45%) subgroups and assessed. The mean follow-up period was 4.4 years (range, two to eight years). Type I fractures were usually torsion injuries, whereas Types II and III fractures were associated with violence (i.e., motor vehicle accident or fall from a height). Types I and II pylon fractures proved to be amenable to open reduction and restoration of anatomic position, stable internal fixation, early joint motion, and delayed weight bearing. Over 80% of these patients had satisfactory function. Nonanatomic reduction, unstable fixation, infection, nonunion, malunion, and secondary arthrosis were associated with disability from Type III pylon fracture treatment. Only 32% of Type III pylon fracture patients had satisfactory joint function. PMID- 2917445 TI - The role of the orthopedist in injury prevention. AB - Injury is an endemic disease process that is a leading cause of death and the leading cause of disability in the United States today. Among physicians, the orthopedic surgeon is most likely to be consulted by injured patients. Traditionally, orthopedists have played an important role in injury prevention as exemplified by the field of sports medicine. Three mechanisms have been demonstrated to be effective means of controlling the injury problem: (1) persuading persons at risk of injury to alter their behavior; (2) requiring individual behavior changes by law or administrative rule; and (3) providing automatic protection by product and environmental design. Specific strategies for implementing injury-prevention programs by the orthopedic surgeon are physician education, patient education, and public education. PMID- 2917446 TI - The role of standard roentgenograms in the evaluation of instability of pelvic ring disruption. AB - Anteroposterior pelvic roentgenograms of 154 patients with pelvic ring disruptions were evaluated to assess their value in the determination of pelvic instability. Three different categories of stability were roentgenographically recognizable: (1) stable, characterized by impacted vertical fracture of the sacrum, nondisplaced fracture of the posterior sacroiliac complex, and/or subtle fractures of the upper sacrum evidenced by asymmetry of the sacral arcuate lines; (2) unstable, characterized by hemipelvic cephalad displacement exceeding 0.5 cm, sacroiliac joint diastasis exceeding 1 cm and/or sacral or iliac diastatic fracture exceeding 0.5 cm; and (3) indeterminate (that is, suspicious but not diagnostic of pelvic instability), characterized by cephalad hemipelvic displacement of less than 0.5 cm, sacroiliac joint diastasis less than 1 cm, and/or diastatic fracture of the sacrum or ilium of less than 0.5 cm. Correlation of the standard roentgenographic, computed tomographic, and clinical orthopedic examinations revealed that pelvic stability was accurately evaluated on the standard pelvic roentgenograms in 88% of cases. Disruptions were stable in 70%, unstable in 18%, and suspect in 12% of patients, for whom adjunct roentgenographic and clinical examinations were required. Determination of pelvic stability in the manner described allows immediate identification of patients with a stable or unstable pelvic injury, as well as identification of those with indeterminate stability requiring further clinical or roentgenologic evaluation. Immediate recognition of pelvic instability on standard pelvic roentgenograms obviates the need for additional diagnostic studies that unnecessarily delay the institution of emergency therapeutic measures designed to control associated hemorrhage. PMID- 2917447 TI - Intramedullary devices for tibial fracture stabilization. AB - Reamed tibial nails that allow interlocking have been the most significant recent advance in the management of tibial fractures. Interlocking nails have expanded the indications for intramedullary fixation to include most nonarticular tibial fractures. Regardless of the amount of comminution, tibial fractures extending from just distal to the tibial tuberosity to 5 cm above the ankle joint may now be safely stabilized with interlocking nail devices. PMID- 2917448 TI - Compartment syndromes of the lower leg. AB - Increased lower-leg intracompartmental pressure compromising neuromuscular function within that compartment is termed compartment syndrome. This condition may be acute (often trauma induced) or chronic (usually exercise related). In a conscious, alert patient, acute compartment syndromes usually are easy to diagnose clinically; however, in the unconscious patient, a diagnostic aid such as the intracompartmental pressure monitor is useful. Using the slit catheter device, compartmental pressures in excess of 30-35 mmHg in a normally perfused patient suggest the need for open compartment fasciotomy. Chronic compartment syndromes require dynamic pressure measurements for an accurate diagnosis. The most important parameters are elevated postexercise pressures and delayed restoration of normal compartmental pressures. Subcutaneous fasciotomy may be sufficient in accurately diagnosed cases of chronic compartment syndrome. PMID- 2917449 TI - Pretreatment arbitration agreement: if you haven't done it right, you haven't done it at all! PMID- 2917450 TI - Nadolol in the treatment of aggressive behavior associated with schizophrenia. PMID- 2917451 TI - Hyperthermia associated with bretylium tosylate injection. PMID- 2917452 TI - Use of i.v. immune globulin for presumed quinidine-induced thrombocytopenia. PMID- 2917454 TI - Lack of chemical peritonitis after intraperitoneal use of two brands of vancomycin hydrochloride. PMID- 2917453 TI - Naloxone therapy in stroke. PMID- 2917455 TI - Attitudes of two groups of dentists towards dental hygienists. AB - The purpose of the study was to assess whether cooperation with a dental hygienist was based on pursuit of financial gain or on aspirations to improve patient care. To this end a questionnaire was sent to 972 dentists. 412 dentists replied, of whom 178 had patients treated by a dental hygienist. Questions were asked regarding practice profile, preventive orientation and dentists' opinion about the material and immaterial value of cooperation with a dental hygienist. Discriminant analysis showed that the main distinguishing factor between dentists who did and dentists who did not cooperate with dental hygienists was their opinion about the quality of the dental hygienists' work in relation to the non financial costs for patients, insurance companies, and dentists. The difference in the dentists' opinions about the direct profitability of dental hygienists was not significant. The conclusion can be drawn that the orientation of Dutch dentists towards care for their patients plays a more important role in a dentist's decision to cooperate with a dental hygienist than is usually presumed. PMID- 2917456 TI - Dental knowledge, attitudes, and behaviors of Indochinese and Australian-born adolescents. AB - Since 1975 more than 100,000 Indochinese refugees have settled in Australia. This study compared the dental health knowledge, attitudes, and behaviors of 131 Indochinese and 107 Australian-born adolescents from a state high school in Melbourne, Victoria. The Australian-born subjects demonstrated the highest level of dental knowledge, and the Kampuchean/Laotian subjects the least. Of the three birthplace groups (Australia, Vietnam, Kampuchea/Laos), the Kampuchean/Laotian group were more likely to believe that their dental health was controlled by external forces. The Kampuchean/Laotian group presented the highest proportion of subjects believing they needed dental treatment. In contrast, however, the Kampucheans and Laotians had the lowest perceived value of preventive dental visits with the Australian-born adolescents presenting the highest proportion. The dental health behaviors of the Kampucheans and Laotians were generally the least favorable and those of the Australian-born subjects the most favorable, although all groups were well short of the conventional ideal. One-third of the Kampuchean and Laotian subjects said they had never been to the dentist before. Few Indochinese subjects claimed to be regular visitors to the dentist. Analysis of data using the framework of the Health Belief Model provided little explanatory power in predicting preventive behaviors. A greater understanding of cultural variations between ethnic groups and targeted dental health education programs would appear to be beneficial strategies for improving oral health of high risk adolescents. PMID- 2917457 TI - A dental survey of Tibetan children in Dharamsala. AB - Since their exodus in 1959 about 100,000 Tibetans have settled in disparate communities in northern India and Nepal. This study describes the dental health of 243 Tibetan children in Dharamsala, in the State of Himachal Pradesh, India. Only 20% of 6-yr-olds were caries-free in the primary dentition while 96.9, 53.3, and 22.4% of 6, 12, and 15-yr-olds were caries-free in the permanent dentition respectively. The DMFT of 12-yr-old children was 1.1, while 15-yr-old children had a DMFT of 3.1. While plaque and calculus were present in many sextants, there was little intense gingivitis and signs of advanced periodontal diseases were rarely present. Almost no dental care had been received. Appropriate dental health promotion activities are discussed. PMID- 2917458 TI - Alveolar bone loss and crowding in adult periodontal patients. AB - The present study aimed to examine whether local crowding and tooth angulation in the mandibular incisor region led to alveolar bone loss in patients with moderate periodontal disease. The sample comprised 27 patients from the Department of Periodontology aged 29-57 yr. Mesiodistal tooth angulation and crowding, defined as an overlap of 2 mm or more, were assessed from dental casts. Alveolar bone loss was assessed from intraoral standardized paralleling radiographs by two methods, the absolute bone level (ABL), recorded from the cementoenamel junction, and the relative bone level (RBL), a new measure, expressing the bone level relative to the two adjacent interradicular crests. Contralateral sites were used as controls. A significant difference in bone level was found between crowded and non-crowded sites by both methods (-1.7 mm, P less than 0.001). This indicates that in periodontal patients local crowding and tooth angulation predisposes to increased bone loss. Analysis of the correlations between tooth angulations and the two measures of bone loss indicated that the RBL value is a more sensitive measure of localized bone loss. PMID- 2917459 TI - Anaerobic threshold. AB - The general interest in the application of exercise testing to evaluate the work capacity or change in the functional ability of individuals has resulted in the development of a variety of non-invasive tests and test parameters such as the anaerobic threshold. This paper presents a computer program written in BASIC that determines the anaerobic threshold from expired respiratory gases collected from an incremental exercise test. Results are summarized in tabular as well as graphical format. The use of the incremental exercise test in conjunction with this computer program provide another means of efficiently determining the exercise capability of the patient. PMID- 2917460 TI - A microcomputer-based system for multi-channel neurophysiological recording. AB - A set of software utility programs is described which, in association with a microcomputer and a commercially available analog-to-digital converter may be used to acquire, store, manipulate and display large amounts of behavioral and/or physiological data in digitized form. PMID- 2917461 TI - Value of clinical features for distinguishing myxedema ascites from other forms of ascites. AB - The diagnosis of myxedema ascites is often difficult and delayed, from our experience and the reports of other investigators. To address this situation, previous reports on the diagnosis of ascites were pooled in order to distinguish the features of myxedema ascites from other forms of ascites. These features were confined to variables that would be obtained routinely from patients with ascites requiring paracentesis. The data of 26 patients with myxedema ascites, and 61 patients with ascites from another cause were analyzed. Discriminant analysis was used to select the variables that best separated patients into myxedema and non myxedema groups. The variables selected were if the ascites was straw-colored or with a protein content less than 2.5 g/dl, if the patient was over age 40, and if there was periorbital edema or hepatomegaly. These variables correctly classified 90.8% of patients. However, considering the roughly 1% prevalence of myxedema ascites among patients with ascites, the predictive value of these variables, in combination, is only 8.7%. With this low rate, these variables should probably not be used to screen for myxedema ascites. PMID- 2917462 TI - Statistical evaluation of agreement between two methods for measuring a quantitative variable. AB - Methodologic research is often concerned with determining whether two methods (procedures, laboratory instruments) can be used interchangeably for measuring some quantitative variable of interest. Logically, one method can be used as a surrogate of another provided the methods show high agreement on the measured results. Although the product-moment correlation (r) is often used as an indicator of agreement, this index is in fact inappropriate for this purpose. The intraclass correlation (r1) is the correct statistic for assessing agreement or consistency between two methods. Another criterion sometimes used for supporting interchangeability is the similarity of the mean measured results obtained by the two methods. However, similarity of means (aggregate agreement) does not necessarily indicate individual-subject agreement, and it is the latter that is the pre-requisite for interchangeability. On the other hand, a marked difference between two means (lack of aggregate agreement) does necessarily indicate lack of individual-subject agreement and therefore non-interchangeability. Herein we suggest that two methods for measuring a quantitative variable can be judged interchangeable provided all of the following conditions are met: first the methods must not exhibit marked additive or nonadditive systematic bias; second the difference between the two mean readings is not "statistically significant"; third, the lower limit of the 95% confidence interval of the intraclass correlation is at least 0.75. Statistical procedures to evaluate these conditions of interchangeability are described in detail. A computer program coded in SAS to carry out the procedures is listed in the Appendix. A similar program coded in DBASE III PLUS for the microcomputer is available upon request. PMID- 2917463 TI - A new method for the classification of subvigil stages, using the Fourier transform, and its application to sleep apnea. AB - An online classification for two-second segments of the EEG is developed. Based on the calculation of a norm and three characteristic frequencies the automatic classification shows satisfactory agreement with visual classification. The influence of the Fourier phase spectra is discussed. Trajectories in the parameter space are introduced. The automatic classification was applied to patients with a pronounced sleep-wake disorder and proved to be valuable in the diagnosis of a disturbed sleep structure. PMID- 2917464 TI - Biological activity of LH during the peripartum period and the estrous cycle of the ewe. AB - Biological activity of luteinizing hormone (LH) is related to the degree of glycosylation of the glycoprotein hormone. The objectives of this study were to determine changes in biologically (BLH) and immunologically (ILH) active LH concentrations in plasma (in vitro bioassay and radioimmunoassay, respectively) and in the ratio of BLH to ILH (B:I) during the peripartum period and during the estrous cycle of the ewe. Blood samples were collected daily 4 days before through 4 days after parturition and during one estrous cycle. Also, samples were collected at 15-min intervals for 6 hr on Days 3 and 12 of the estrous cycle to quantify the influence of an elevated plasma concentration of progesterone (P) on the episodic secretion profiles of BLH. Progesterone concentration was determined on the 4th days pre- and post-partum, on each day of the estrous cycle and at hourly intervals on Days 3 and 12 of the cycle to investigate the hypothesis of an inverse relationship between P and BLH. The BLH and ILH concentrations were low during the peripartum period, and the B:I ratio did not increase by the 4th day postpartum. Mean ILH concentration was greater (P less than .05) in the postpartum than during the prepartum period. During the estrous cycle, mean daily B:I ratio was consistently above unity except for the day of estrus. The pre ovulatory LH surge (BLH and ILH) was associated with a decrease (P less than .05) in the mean B:I ratio to 0.0065. Mean concentrations of BLH and ILH in plasma samples collected every 15 min on Day 12 were similar to Day 3 of the cycle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2917465 TI - Clenbuterol-induced desensitization in murine adipocytes: relationship to in vivo effectiveness. AB - In vitro lipolytic response of isolated murine fat cells to epinephrine (EPI) or clenbuterol (CB) was used to evaluate the potential for the beta 2-adrenergic agonist, CB, to induce cellular resistance to further beta-adrenergic stimulation. Feeding CB (20 mg/kg diet) to mice for 1, 3 or 6 wk decreased adipocyte sensitivity to EPI or CB by 35-45%, with no differences in magnitude of this desensitization across time. Basal and maximal rates of lipolysis were similar for control- and clenbuterol-fed mice. In agreement with the feeding studies, a 2 hr preincubation of control-fat tissue with either 10 microM EPI or 100 microM CB, followed by adipocyte isolation and restimulation with EPI, reduced adipocyte sensitivity by 50%. In addition, maximal rates of lipolysis were decreased 24% and 34% for EPI and CB treated tissue, respectively. The similar adaptive responses of the adipocytes to CB exposure in vivo or in vitro suggest that CB interacts directly with fat cells in vivo and can induce tolerance. Mice fed CB for 12 wk had 33% smaller epididymal fat pads compared to controls, but pad weight differences were only 10% if feeding of CB was discontinued 1 wk before the 12 wk analysis. The reversal in fat pad gain with a 1 wk removal of CB from the diet indicates at least partial effectiveness of CB through 12 wk. The modest beta-adrenergic desensitization established by wk 1 was similar on wk 6 suggesting that CB-induced adipocyte resistance is of little consequence to the fat-reducing properties of CB administration. PMID- 2917466 TI - Characterization of secretion of thymosin alpha 1 and thymosin beta 4 during prepuberty, estrus and pregnancy in the bovine female. AB - The objective of the present study was to characterize secretion of thymosin alpha 1 (A1) and thymosin beta 4 (B4) during different stages of ovarian function and pregnancy in bovine females. One hundred and thirty-five prepubertal heifers averaging 9 mo of age at the time the study was initiated were used. Estrous detection was conducted twice daily using intact bulls fitted with marking harnesses. Blood samples were collected at first behavioral estrus and at the time of rectal palpation for pregnancy. Heifers were weighed at the beginning of the study and every 56 days and additional blood samples were collected at those times. Plasma was harvested and radioimmunoassays were conducted to quantify concentrations of thymosin A1 and B4. Mean concentrations of thymosin A1 and thymosin B4 were determined during prepuberty, estrus during which conception did not occur, estrus during which conception did occur, pregnancy and in heifers that failed to attain puberty. Mean plasma concentrations of thymosin A1 and B4 were greater at estrus during which conception occurred than at any other period (P less than .01). Regressions of days prepubertal and days post conception on thymosin A1 and B4 were analyzed. During the 100 days prior to puberty, thymosin A1 and B4 did not change in the heifers that ultimately conceived. However, in the heifers that were never determined to be pregnant by rectal palpation, concentrations of both thymosin A1 and B4 increased linearly during prepuberty (P less than .01). A decline in thymosin A1 and B4 concentrations occurred in a quadratic fashion from conception through the first 100 d of pregnancy (P less than .01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2917467 TI - Quantitation of calmodulin in the mammary gland of the lactating sow. AB - It has been suggested that calmodulin, a calcium-binding protein, has a functional role during milk secretion. High levels of calmodulin are present during lactation in rat mammary glands and a substantial increase has been observed in the bovine mammary gland prior to parturition. In the sow, regressed glands involute while suckled glands remain highly active even though they are under the same hormonal influence. In this study, tissue samples were taken from suckled and regressed glands of the same sow at both peak and late lactation. Calmodulin and total protein were measured in tissue homogenate supernatants. Residual milk was apparent in regressed glands during mid lactation but not in the same glands by late lactation. Calmodulin levels in tissue were the same for both suckled and regressed glands. There was a slight but non-significant increase in the tissue calmodulin level from peak to late lactation. Protein levels declined significantly from mid to the late stage of lactation. There was no change in protein level between the suckled and regressed glands. Calmodulin may be responsible for casein phosphorylation and/or the mediation of prolactin action on the gland. The precise regulatory mechanisms relating hormonal control to calmodulin levels during lactation need further investigation. PMID- 2917468 TI - Occurrence of sexual behaviour related to the risk of HIV-infection. A survey among Danish men, 16-55 years of age. AB - To describe the occurrence of sexual behaviour involving increased risk of HIV infection in a representative sample of Danish men, 16-55 years of age, a self administered anonymous questionnaire was distributed in connection with a personal health interview and returned by mail. The response rate was 55% corresponding to 1,155 participants. The sexual behaviour of 33% of the men was potentially risky, with a chance of HIV-infection. Homosexual experience was reported as 3% and sexual contact with female prostitutes as 14%. During the previous twelve months, 1% had had homosexual contact, 2% had had contact with prostitutes, and 22% had more than one female partner; most of these men had "one night stands" and used condoms infrequently. Consequently, a significant minority of the participants engaged in sexual behaviour which might facilitate the dissemination of HIV-infection. Although the prevalence of HIV among heterosexuals in Denmark is low, intense health education will be needed in order to prevent heterosexual spread of HIV in the future. PMID- 2917469 TI - 31st Annual Aspen Lung Conference: Infections and the lung. Aspen, Colorado. PMID- 2917471 TI - Two statistical approaches to nuclei shape and size in a morphometric description of lymph node sections in non-Hodgkin's lymphoma. AB - An attempt is made to evaluate more clearly the potential contribution of quantitative nuclear profile shape and size measurements to lymph node section histologic description in 70 cases of non-Hodgkin's lymphoma (NHL). The area of nuclear profiles and five nonredundant and size-free shape indices were measured using the THECLA program on a Leitz Texture Analysis System (Leitz-TAS). Two statistical approaches were applied, known respectively as "parametric," (first statistical moments of variable distributions over samples of 200 nuclear profiles) and "nonparametric," which are percentages of nuclear profiles distributed into five "cytological" classes that are defined by shape: round (A), elongated (B), kidney shaped (C), irregular (D) and cleaved (E) nuclear profiles. Both statistical approaches provide proper overall discrimination of the eight histological categories identified with reasonable reliability by pathologists. Above all, the present report discusses the ability of a set of parametric and nonparametric variables to describe NHL cell populations, in an objective and meaningful way, according to nuclei shape. A method of synthesizing multidimensional correlations (CORICO program) is proposed in support of the discussion. Also, the specific descriptive power of each of the variables is described; in particular, it is concluded that there is a close link between the shape and size of the nuclear profiles of the cells. PMID- 2917470 TI - Cyanine dye labeling reagents containing isothiocyanate groups. AB - New isothiocyanate derivatives of cyanine dyes were synthesized as fluorescent covalent labeling reagents for proteins and other biomolecules. These dyes have maximum absorbance in the red and near infrared regions of the spectrum, have high extinction coefficients and have adequate quantum yields. Incorporating two alkyl sulfonate groups in the dye structures increases their water solubility, which is beneficial for labeling biological molecules in aqueous solution. Reactivities of proteins with these new cyanines are similar to their reactivities with fluorescein isothiocyanate. These new labeling reagents are complementary to the fluorescein and rhodamine reagents, expanding the possibilities of multicolor analyses. Sheep anti-mouse-IgG antibody was labeled with a pentamethine cyanine dye (CY5.8-ITC) and used with a fluoresceinated antibody as a second reagent for detecting human T-cell subsets by flow cytometry. PMID- 2917472 TI - Cyanine dye labeling reagents for sulfhydryl groups. AB - Cyanine and merocyanine dyes are introduced as new fluorescent reagents for covalently labeling proteins and other biomolecules. These dyes, which contain iodoacetamide functional groups, have high extinction coefficients and moderate quantum yields. A major advantage of these polymethine dyes is the easy manipulation of their spectral properties during synthesis. Cyanines containing reactive functional groups can be made with absorption maxima ranging from less than 500 nm to greater than 750 nm. This property opens additional regions of the spectrum for experiments involving the simultaneous multicolor analysis of different fluorescent probes. The cyanines, which are relatively insensitive to solvent property changes, are complemented by the merocyanines, which are keen indicators of solvent polarity. PMID- 2917473 TI - Quantitative morphological analysis of adriamycin-resistant human K562 leukemic cells. AB - The morphological changes associated with Adriamycin resistance in a human leukemic cell line have been investigated by image analysis. An Adriamycin resistant subline of the human erythroleukemic K562 cell line has been established. Three sets of cells have been analysed: sensitive cells, resistant cells cultured in the continuous presence of Adriamycin, and resistant cells cultured without the drug. Image analysis shows that Adriamycin-resistant K562 cells display significant morphological changes as compared with sensitive cells, at both the nuclear and cytoplasmic levels. These changes make it possible to separate sensitive and resistant cells automatically and with a classification accuracy of 76% and only four cytological parameters. Image analysis may therefore offer an interesting tool for studying drug resistance in leukemic cells, from both an experimental and a clinical point of view. PMID- 2917474 TI - Comparison between flow cytometry and fluorometry for the kinetic measurement of membrane fluidity parameters. AB - Steady-state fluorescence polarization measurements obtained with a flow cytometer were compared with those obtained with an SLM subnanosecond fluorometer. Measurements were made over time after exposure of HeLa cells to the membrane probe 1,6-diphenyl-1,3,5-hexatriene (DPH), 1-[4-(trimethylamino)phenyl] 6-phenyl-1,3,5-hexatriene (TMA-DPH), or [12-(9:anthroyloxy) stearate (12-AS). After 1 min, anisotropy values of 0.28 (DPH), 0.28 (TMA-DPH), and 0.21 (12-AS) were obtained. Thereafter, the anisotropy of DPH- and 12-AS-labelled cells rapidly decreased (0.18 and 0.12 after 5 min), while that of TMA-DPH-labelled cells changed only slightly (0.27 after 30 min), suggesting that DPH and 12-AS, unlike TMA-DPH, do not remain anchored in the HeLa plasma membrane, but translocate to more fluid environments inside the cell. These suggestions were confirmed by visual observation with fluorescence microscopy. There was no significant difference between the results obtained with the flow cytometer and those obtained with the fluorometer. PMID- 2917475 TI - Characterization by flow cytometry of fluorescein-methotrexate transport in Chinese hamster ovary cells. AB - We have studied by flow cytometry the transport of fluorescein-methotrexate in Chinese hamster ovary cells. Fluorescein-methotrexate appears to enter cells via a mechanism different from the carrier-mediated system for methotrexate. This conclusion is supported by the following observations: 1) Fluorescein methotrexate is transported equally well into normal and mutant cells defective in the inward methotrexate uptake. 2) Folic acid and its reduced states, which competitively inhibit methotrexate uptake, do not alter fluorescein-methotrexate transport. 3) Fluorescein-methotrexate accumulation exhibits a low temperature coefficient (Q10 = 1.6) compared with the influx of methotrexate (Q10 = 6-8). 4) Initial rates of fluorescein-methotrexate uptake are concentration dependent but are not saturable. 5) Fluorescein-methotrexate uptake is very slow and reaches steady state after 8 h, whereas at an equimolar concentration methotrexate reaches saturation after 20 min. 6) Initial influx rates of fluorescein methotrexate are not affected by the presence of methotrexate. 7) Sulfhydryl reactive mercurials, which block methotrexate transport, do not reduce fluorescein-methotrexate influx, but rather stimulate it. Thus, based on the nonsaturability of fluorescein-methotrexate inward transport, its low temperature coefficient, and lack of inhibition with structural analogs, we conclude that fluorescein-methotrexate is accumulated in hamster cells by a passive diffusion process. PMID- 2917476 TI - The Multivariate Prognostic Index and nuclear DNA content are independent prognostic factors in primary breast cancer patients. AB - The predictive value of a previously described Multivariate Prognostic Index (which incorporates weighted values of the mitotic activity index, tumor size, and the axillary lymph node status), and the nuclear DNA content (DNA) was evaluated in 156 patients with primary invasive ductal breast cancer, diagnosed between 1980 and 1983. The results were analysed with respect to the occurrence of distant recurrence and survival of the patients after at least 3 yr of follow up (range 36-73 months; median 44 months). Known prognostic factors such as lymph node status, tumor size, and the mitotic activity index correlated independently with distant recurrence. Furthermore, in respect to survival, the investigated prognostic factors (except DNA content) were significantly correlated. The results indicate that the predictive value of the Multivariate Prognostic Index (MPI) is stronger (P less than 0.001) than of the nuclear DNA content (P less than 0.005) with respect to distant recurrence. In a Cox multivariate regression analysis DNA ploidy turned out to be an independent prognostic factor once the MPI was selected. Furthermore, in Cox's analysis, DNA ploidy was the fourth selected variable after lymph node status, mitotic activity index, and tumor size in individual parameter analysis. The results of this study indicate that, with respect to breast cancer screening programs, it seems worthwhile to integrate morphometric features, the MPI, and DNA ploidy in a new prognostic model. PMID- 2917477 TI - Ternary representation of trivariate data. AB - A new fast trivariate display technique based on the ratio of three measured variables and of relative cell number, obtained from flow cytometric measurements, is described. PMID- 2917478 TI - Comparison of fresh, ethanol-preserved, and paraffin-embedded samples in DNA flow cytometry. AB - Fresh, ethanol-preserved, and formalin-fixed and paraffin-embedded samples taken from the same part of 15 human tumors, and from one normal spleen and one pancreas were analyzed for nuclear DNA content by flow cytometry. The coefficient of variation (CV) values of the G1 peaks were smaller in the fresh than in the other samples (P less than 0.001). The DNA ploidy of the tumors was the same in all types of samples. The DNA indices (DIs) measured from either ethanol preserved or formalin-fixed tissue correlated strongly with those obtained from fresh tissue (P less than 0.001), although they tended to be somewhat smaller in the fresh samples. The S-phase fractions measured from all types of samples were of the same order of magnitude in most cases (P less than 0.001). Uninterpretable histograms were most often obtained from fresh samples. Identical DI values and rather constant S-phase fractions were obtained from ethanol-preserved samples stored at 4 degrees C for up to 5 months. It is concluded that all three types of samples are suitable for the determination of DNA ploidy, DI, and S-phase fraction and that 50% ethanol is suitable for long-term preservation of flow cytometric samples. PMID- 2917479 TI - A simple preservative for flow cytometric DNA analysis. AB - A solution containing citric acid buffered saline (CABS) and 99% ethanol (E) 1:1 was used for preserving cells for flow cytometric DNA analysis. DNA histograms obtained from fine needle biopsy aspirates and preserved in CABS+E had a similar mean coefficient of variation (CV) as was obtained from aspirates taken in CABS (3.3 vs. 3.4%) and a clearly smaller mean CV than was obtained from aspirates preserved in 50% ethanol (mean 4.8%, P less than .0001). Aspirates taken in CABS more often contained a small (less than 3,000) number of cells as compared with aspirates preserved either in CABS+E or ethanol (P less than .0001). Since preservation of cells in CABS+E allows long-term storage of samples and results in a decreased number of insufficient samples as compared with buffered saline and in an enhanced resolution as compared with 50% ethanol, CABS+E is recommended for preservation of cytological samples to be analyzed for DNA content with flow cytometry. PMID- 2917480 TI - [Treatment of otherwise incurable tumor diseases in childhood using whole-body hyperthermia and chemotherapy]. AB - Conventional methods of treatment having failed in 17 children (aged 9/12 to 16 5/12 years) with incurable solid malignant tumours underwent whole-body hyperthermia (41.8-42.0 degrees C, for 2-3 h), hyperglycaemia (20-25 mmol/l) and polychemotherapy. Five children had neuroblastoma (stage 4), three Wilm's tumour (stage 4 or 5, unfavourable histology), five skeletal sarcoma with metastases, three inoperable malignant liver tumour, and one brainstem tumour of unknown histology. Whole-body hyperthermia was induced by extracorporeal blood warming in an haemodialysis apparatus under neuroleptic analgesia, thermistors measuring the temperature in the oesophagus, rectum, trachea and skin. There were on average four treatment sessions (between one and ten, total 58), a week apart. The result could be assessed in 12 children: one persisting complete remission (19 months metastasising renal rhabdoid tumour), eight partial or incomplete remissions, and three nonresponders (osteogenic sarcoma; Ewing sarcoma; brainstem tumour). If the risk can be satisfactorily judged the method is useful and of bearable toxicity. The results point to a high antitumour effectiveness of combined hyperthermia and chemotherapy. PMID- 2917481 TI - [Papaverine-induced priapism. Experiences with a new urologic emergency]. AB - Ten patients with priapism after self-administered intracavernous papaverine injection for erectile impotence had to be treated as emergencies between September 1985 and February 1988. In half the patients it was possible to achieve penile detumescence by puncture of the corpora cavernosa, injection of 2-5 mg metaraminol or both, but failed in the remainder, requiring the intracavernous injection of 10-30 mg metaraminol in 500 ml physiological saline. Surgical treatment was necessary in one case. Papaverine-induced priapism constitutes a urological emergency which, because of the danger of hypertensive crises, demands treatment in hospital. PMID- 2917482 TI - [Diabetic retinopathy]. PMID- 2917483 TI - [Corpora cavernosa autoinjection therapy. Potency at any price?]. PMID- 2917484 TI - [Nephritis from 5-aminosalicylic acid]. PMID- 2917485 TI - [Serum beta-carotene: a simple static laboratory parameter for the diagnosis of steatorrhea]. AB - The value of serum beta-carotene concentration as an indicator of steatorrhoea was investigated in 50 patients with steatorrhoea (fecal fat greater than 7 g/day), 53 controls, and 22 patients with gastrointestinal disease without steatorrhoea. In the control group, beta-carotene concentrations were normally distributed when plotted logarithmically. The mean value was 131 micrograms/dl. The lower limit of normal, based on a 2-SD confidence interval, was 47 micrograms/dl. beta-Carotene concentrations and fecal fat excretion were correlated in a reciprocal, hyperbolic function (r = -0.66). Twenty-nine of the 50 patients with steatorrhoea had beta-carotene concentrations less than 47 micrograms/dl (sensitivity 58%; specificity 93%). Referring to an additional cut off point of 100 micrograms/dl, beta-carotene concentration had a sensitivity of 88%. These data show that low plasma beta-carotene concentrations (less than 47 micrograms/dl) can be regarded a specific and useful indicator of steatorrhoea and thus obviate fecal fat analysis. Values greater than 47 micrograms/dl, however do not exclude steatorrhoea. Based on a two-step interpretation beta carotene is thus both a useful screening test for steatorrhoea (with a cut-off point of 100 micrograms/dl) and, more important, a valid, simple, and clinically practical alternative for fecal fat analysis (if values are less than 47 micrograms/dl). PMID- 2917487 TI - [Chronic aluminum poisoning in continuous ambulatory peritoneal dialysis: treatment with deferoxamine]. AB - After six years of home haemodialysis and two years of continuous ambulatory peritoneal dialysis a 59-year-old woman developed an aluminium-induced osteopathy, myopathy and normochromic anaemia. She was at first treated with intravenous, then peritoneal, deferoxamine, 1 g every other day. Before treatment, 15.8 micrograms aluminium (Al) had been eliminated daily, with a peritoneal clearance of 0.3 ml/min; after intravenous deferoxamine a mean of 774.3 +/- 102.3 micrograms Al was eliminated per day, after peritoneal deferoxamine 646.7 +/- 89.6 micrograms of Al per day, with a peritoneal clearance of 2.2 +/- 0.9 (intravenous) and 1.9 +/- 0.7 ml/min (intraperitoneal). After four months of deferoxamine administration, mostly intraperitoneally as an out patient, the osteomalacia clearly improved, as did the myopathy and anaemia. PMID- 2917486 TI - [Catheter valvuloplasty in mitral valve stenosis]. AB - Balloon dilatation of the mitral valve was performed, trans-septum via the femoral vein or retrogradely via the femoral artery, in 20 patients, aged 31-65 years, with post-rheumatic mitral stenosis. Haemodynamically insignificant mitral regurgitation occurred in two patients. In one patient a permanent atrial septal defect was produced by the transseptal puncture. In a fourth patient severe mitral regurgitation occurred which required operation. There were no other serious complications. No dilatation was possible in three patients for technical reasons. Successful dilatation was achieved in 16 of the 20 patients. The end diastolic transvalvular pressure gradient was reduced from 12 +/- 5 to 4 +/- 3 mm Hg. At follow-up, after 3-6 months (12 patients) or after 1-1.5 years (5 patients), in one instant after a second dilatation, a lasting good result was confirmed, the mean end-diastolic gradient being 4 +/- 3 mm Hg. PMID- 2917488 TI - [Sacroiliitis caused by Brucella melitensis]. AB - Technetium scintigraphy established sacroiliitis in a 21-year-old man who had complained of hip pain for two weeks. Brucella melitensis was cultured from hip joint fluid. He was treated with 160 mg trimethoprim and 800 mg sulphamethoxazole, three times daily for six weeks. He also had prophylactically 600 mg rifampicin daily by mouth for the last three weeks. He was symptom-free four weeks after onset of treatment. At follow-up one year later there was no sign of recurrence. Brucella titres and blood sedimentation rate were within normal limits. PMID- 2917489 TI - [Standards in the surgery of colorectal carcinoma]. PMID- 2917490 TI - [Liability after death for treatment mistakes]. PMID- 2917491 TI - The value of hormonal measurement in gynaecological practice. PMID- 2917492 TI - The pattern of chronic gastric ulcer at Kenyatta National Hospital (K.N.H.). AB - Thirty consecutive patients with gastric ulcer diagnosed during upper gastrointestinal fibreoptic panendoscopy at both Kenya Medical Research Institute and Kenyatta National Hospital endoscopy rooms were studied. The male/female ratio was 5:1 with a peak prevalence in the 6th decade. 76.6% of the patients were from the Kikuyu ethnic group. Smoking habit was found in only 50% of patients with gastric ulcers. There were a total of 32 gastric ulcers in 30 patients. 84.4% of these were at the incisura angularis. All the incisural ulcers were benign. Two (6.25%) of the 32 ulcers were malignant (one at the cardia and the other at the antrum). Gastric ulcers whose diameter were greater than 30 mm had a higher tendency of being malignant. Five patients (16.7%) had both gastric (4 benign and 1 malignant) and duodenal ulcers while 4 (13.3%) patients had both gastric and pyloric ring ulcers. Apparent healing of a gastric ulcer while on an H2-antagonist does not totally exclude malignancy. Upper gastrointestinal bleed which was present in 53.3% of cases was the most frequent complication. PMID- 2917493 TI - The possible luteotrophic effect of guinea-pig chorionic gonadotrophin. AB - Studies into human pregnancy have many practical applications such as in fertility regulation. Such studies cannot be done in women for ethical reasons and a suitable animal model has to be identified. Though guinea-pig is known to secrete a CG-like protein, the precise function of this material during early pregnancy has not been elucidated. We assessed the effect of guinea-pig chorionic gonadotrophin (gpCG) on luteal tissue kept in-vitro. This involved short-term culture of the luteal tissue cells and the subsequent measurement of progesterone following challenge with gpCG. Guinea-pig CG stimulated progesterone production by cultured luteal tissue and this suggests that this hormone, as in primates, has a luteotrophic role during pregnancy. We conclude that the guinea-pig provides a useful homologous model for studying early pregnancy events in humans. PMID- 2917494 TI - Studies with choriocarcinoma and normal pregnancy serum chorionic gonadotrophin. AB - Serum obtained from either normally pregnant women or those with choriocarcinoma was pooled and purified by ammonium acetate/alcohol extraction followed by ionic exchange and gel filtration chromatography. The CG activity was monitored using a double antibody radioimmunoassay utilizing anti hCG both as the labelled ligand and standard. Biological activity was measured by the rat luteal cell radioreceptor assay. Both purified preparations exhibited heterogeneity in terms of the behaviour during ionic exchange chromatography and isoelectric focussing. The Stokes radii were 33A and 33.3A for normal pregnancy and choriocarcinoma hCG respectively. Material from both sources focussed between pH 4.5 and 5.5. Relative to the second international hCG standard the immunological activity of normal pregnancy hCG was 9,100 iu/mg and that of choriocarcinoma CG was 10,970 iu/mg. The corresponding biological potencies were 8,190 iu/mg and 7,569 iu/mg respectively. There was a significant difference between the biological to immunological activity of choriocarcinoma hCG (0.69) when compared with that of normal pregnancy CG (0.90). This was confirmed with a subsequent follow up study when individual serum samples from normal pregnancy were compared with those from choriocarcinoma patients (p = 0.01). It was concluded that in a third world situation this significant difference in the ratio of biological to immunological activity may be a useful method for evaluating treatment of choriocarcinoma patients. PMID- 2917495 TI - Percutaneous upper urinary stone surgery. AB - Fifty-five patients underwent surgery for renal and upper ureteric stones in the department of urology at the Royal Infirmary in Glasgow, Scotland, during a one year period beginning in October 1986. There were 31 males and 24 females, with a mean age of 47.7 years. The targeted stones were successfully removed in 46 (83.6%) patients. 52.7% of the patients were discharged home within 4 days of operation. Minor perforations of the renal collecting system was the commonest complication, which occurred in 6 patients. Three patients had serious haemorrhage, one of them requiring nephrectomy for bleeding from a torn renal vein. One patient had cardiac arrest on post operative day 3, suffered brain damage, and died on day 10. Percutaneous lithotomy has become a well-established, effective method of treating upper urinary stones. Costly equipment is involved, however, and critical assessment is required in deciding to introduce this technique of stone treatment in a developing country. In those circumstances a gradual assimilation is suggested. PMID- 2917496 TI - Forcefeeding practices and otitis media in Ilorin, Nigeria. AB - Six hundred and ten mothers were interviewed with respect to forcefeeding. 390 (64.37%) forcefed their children. Refusal of feeds (86.9%) was the main reason given by mothers necessitating forcefeeding. 139 (35.5%) of the mothers had experienced one child or the other aspirating the feeds during forcefeeding. 22 (8.2%) of the forcefed children had otitis media while only 12 (5.5%) of those who were not forcefed had otitis media. The difference was significant (p less than 0.05). There is a strong association (p less than 0.001) between forcefeeding and level of formal education. PMID- 2917497 TI - The clinical pattern of duodenogastric bile reflux in the Kenyan Africans. AB - Forty consecutive African patients found to have duodenogastric bile reflux at endoscopy were studied. Bile reflux was found more commonly among males than females, giving a male/female ratio of 2.3:1, with a peak age at 41-60 years. ABO blood groups had no significant influence on duodenogastric bile reflux. Flatulence and borborygmi were the most consistent symptoms other than the classical dyspeptic pain pattern. Bilious vomiting was a rare finding. Duodenogastric bile reflux was more commonly associated with endoscopic gastritis (67.5%), gastric ulcer (35%) and oesophagitis (30%) than with duodenal ulcer (22.5%), deformed pyloric ring (5%) or distorted duodenal bulb (2.5%). The dysfunction in the pyloric sphincter in people with duodenogastric bile reflux appears to be more of a physiological defect than structural. PMID- 2917498 TI - "Yesterday, today and tomorrow"--fifty exciting years: the Second Nelson Awori memorial lecture. PMID- 2917499 TI - Cervical cytology in an urban Nigeria population. AB - The prevalence of cytologic abnormality was investigated among two population groups in an urban setting: those responding to a mass cytologic screening campaign and are without symptoms and those referred on account of symptoms or signs suggestive of cervical pathology. Among a total of 1550 clients so screened a 6% incidence of cytologic abnormality was found among the asymptomatic group contrasting with an overall 23% prevalence in the whole group. Even though a prevalence of 90% was found among the early symptomatic group, only 2 cases of CIS was found giving a prevalence of 13/10,000. This suggests cervical screening could prove highly effective in identifying cervical pathology at a significantly highly treatable state in this population. PMID- 2917500 TI - The treatment of compound joint injury. AB - The management and complications arising from compound joint injuries are discussed. A five-part scheme for the treatment of compound joint injuries is presented: 1. Early radical and total primary surgical intervention. 2. Active irrigation drainage. 3. Rigid internal fixation. 4. Prophylactic anticoagulant therapy. The local application of VAB-cream and the use of systemic antibiotics reduced the rate of infection and the period of hospital stay. The best clinical results were attained by patients in group A-B open joint injury, 83 and 84% of whom, respectively, were classified as excellent to good. The study confirmed that the principles were safe and effective; they have general application and depends on the nature of open joint injury. PMID- 2917501 TI - The acute leukaemias in adults in Benin City, Nigeria. AB - Forty-three adult cases of acute leukaemia (AL) seen at the University of Benin Teaching Hospital, Benin City, Nigeria in the 13-year period 1975-1987 have been analysed with respect to the presenting features, management and outcome. The percentage incidence of AML and ALL were 51.2 and 23.3 respectively. There is a preponderance of male patient (male:female ratio was 2.1:1, 2.3:1, 1.3:1, and 3:1 respectively for AML, ALL, BC and ALSCL). Most cases of AL occurred in the 21-30 year age bracket. Pallor (77.3%) is the commonest presenting feature in AML whereas night sweats and lymphadenopathy occurred in most cases of ALL (80%). The main causes of death are haemorrhage and infection. Treatment is generally inadequate and so the results of treatment are poor. PMID- 2917502 TI - Measles in a two-months age baby and his mother in Juba, Sudan. AB - Measles in children 2-5 months of age is a new phenomena not only in Equatorial Juba but in the Sudan at large. It is the first time a baby of two months of age and his mother who had never contracted measles till the age of 17 years have been admitted to Sabah Children's Hospital in Juba. This occurrence may indicate as in other areas where immunisation programmes have been carried out increasing numbers of people will not encounter measles till they reach adolescence or adult life. This could lead to infants being born without usually transmitted antibodies, hence develop infection with measles at an earlier age than has been usual in the past. PMID- 2917503 TI - Difficult and advanced procedures. PMID- 2917504 TI - Manual translaryngeal jet ventilation. AB - The manual translaryngeal jet technique is a safe and reliable method of emergency ventilation, providing adequate gas exchange and high levels of oxygenation for the patient who requires positive pressure breathing. It can be performed more rapidly than other invasive means of airway control and, with close attention to the proper technique, has proved safe and effective in maintaining normal blood gases for prolonged periods. Further work is required to define proper inspiratory-to-expiratory ratios better and to determine whether the technique is protective against aspiration. The equipment and technique should be familiar and readily available to every emergency clinician. PMID- 2917505 TI - The external rotation method for reduction of acute anterior shoulder dislocation. AB - Acute anterior shoulder dislocation is a common disorder confronting the emergency physician. Traditional methods of reduction are often technically difficult, time consuming, and painful to the patient. Furthermore, they frequently require more than one physician and occasionally exacerbate the injury. Conversely, the recently described method of reduction by external rotation is a reliable and safe method. A single physician performs the reduction rapidly and patients tolerate it well. PMID- 2917506 TI - Difficult nasogastric tube insertions. AB - NGT insertion is a procedure that is done frequently in Emergency Departments. A step-by-step procedure has been presented. There are certain circumstances that may make NGT insertion difficult. They are esophageal narrowing, comatose or intubated patients, and patients who have sustained severe facial or skull injuries. A number of strategies have been suggested to facilitate the passage of the NGT. These include generous lubrication, chilling the tube, grasping the alae of the thyroid and lifting anteriorly, using two fingers in the mouth to facilitate passage of the tube, and direct visualization. Complications, although rare, may occur. Examples of complications that are reported in the literature include mucosal ulcerations, submucosal passage of a tube, accidental passage of an NGT into the brain, and esophageal perforation. Generous lubrication, direct visualization, and the use of fluoroscopy, as well as knowledge of these complications, may help to decrease or prevent their incidence. PMID- 2917507 TI - Emergency tracheotomy in patients with massive neck swelling. AB - Immediate control of the airway in a patient with massive neck swelling caused by cervical or maxillofacial trauma is often difficult. A modified new technique, discussed in this article, has been developed based on anatomic principles for the performance of a modified tracheotomy in these patients. PMID- 2917508 TI - Increases in thyroid gland blood flow after hemithyroidectomy in the rat. AB - After subtotal thyroidectomy, the thyroid gland remnant undergoes compensatory alterations in function and morphology. Under the trophic stimulation of elevated plasma TSH concentrations, the thyroid remnant responds with an increase in hormone synthesis and secretion and, in addition, increases in mass. We have examined the alterations in thyroid blood flow which accompany increased secretion and growth after hemithyroidectomy (HTX) in male Sprague-Dawley rats (200-220 g). At various times after surgical HTX (1, 2, and 3 weeks), blood samples for the determination of plasma hormone concentrations were obtained and tissue blood flows were determined using 15 +/- 5 microns diameter 141Ce-labeled microspheres in a modification of the reference sample microsphere technique. The microspheres were injected directly into the left cardiac ventricle via a 23 gauge needle passed through the chest wall while a reference blood sample was collected. After the animals were killed, tissues were cleaned and weighed, then tissue and reference blood sample radioactivities were determined. In addition, thyroidal immunoreactive vasoactive intestinal peptide was measured after acetic acid (0.67 N) extraction. After HTX, plasma TSH concentrations were significantly elevated. The plasma concentrations of T4 and T3 fell, but by less than the expected 50%. The mass of the remaining thyroid lobe increased progressively over the 3 weeks post thyroidectomy, reaching approximately 70% of the total thyroid gland weight of sham-operated controls. Thyroid blood flow per gram of tissue was significantly elevated at all times post HTX. HTX did not induce any alterations in thyroidal immunoreactive vasoactive intestinal peptide concentration. Thus, after HTX, the well documented compensatory alterations in thyroid remnant growth and secretion were accompanied by a prompt and striking increase in thyroid blood flow. PMID- 2917509 TI - The postnatal development of sarcoplasmic reticulum Ca2+ transport activity in skeletal muscle of the rat is critically dependent on thyroid hormone. AB - We investigated the role of thyroid hormone in the postnatal development of Ca2+ transport activity of sarcoplasmic reticulum in skeletal muscle (m. gastrocnemius plantaris). With a Ca2+-stat method using the fluorescent dye fura 2 as Ca2+ indicator, we determined the oxalate-supported maximal Ca2+ uptake activity of sarcoplasmic reticulum in whole muscle homogenates from neonatal rats. Expressed per g tissue wet wt, the activity increased nearly 10-fold during the first 8 weeks after birth, following which time a plateau was reached. This development was absent in hypothyroid pups, in which the level of Ca2+ uptake activity remained constant at 10% of the normal adult value for at least 8 weeks. When the mothers were given 0.05% propylthiouracil in the drinking water 1 week before parturition, these pups ceased to grow after 4 weeks, had a reduced muscle protein content and a characteristic cretinous appearance. The effects of hypothyroidism could be reversed by T3 treatment (0.5 micrograms/100 g BW, daily) starting 1 or 6 weeks after birth. Treatment with bovine GH (0.1 or 0.5 IU/100 g BW; daily) starting on day 5 stimulated body growth, particularly of muscle, but was without effect on the failing development of Ca2+ uptake activity. The postnatal rise in citrate synthase and succinate dehydrogenase activities was impaired in the hypothyroid group, but lactate dehydrogenase and creatine kinase activities rose continuously, although at a reduced rate. T3 treatment also reversed these effects of propylthiouracil. At the higher dosage used bovine GH appeared to stimulate the accumulation of creatine kinase. We conclude that the failing postnatal development of sarcoplasmic reticulum Ca2+ transport activity in hypothyroidism is not secondary to the absence of GH, nor is it part of a general, indiscriminate effect, but, rather, that it indicates an absolute requirement of thyroid hormone for this particular aspect of muscle differentiation. PMID- 2917510 TI - Prostaglandins and progesterone secretion in the in vitro perfused pseudopregnant rabbit ovary. AB - The relationship between progesterone and prostaglandin (PG) secretion in the pseudopregnant rabbit corpus luteum was investigated using isolated in vitro perfused ovaries. Progesterone and PG secretion were measured on days 1, 11, and 18 of hCG-induced pseudopregnancy. The mean progesterone secretion increased significantly from days 1 to 11, and then decreased significantly by day 18. PG secretion was inversely correlated with progesterone secretion, suggesting that PG might inhibit progesterone secretion. To test this hypothesis, indomethacin, an inhibitor of PG secretion, was administered to intact rabbits from days 11-18 of pseudopregnancy and/or on day 18 ovaries were perfused in vitro with indomethacin. Indomethacin administered in vivo, in vitro, or both in vivo and in vitro significantly reduced PG secretion compared to that in controls, but did not affect progesterone secretion. In addition, perfusion of ovaries in vitro with PGF2 alpha did not alter progesterone secretion on either day 11 or day 18. Thus, although there is an inverse relationship between progesterone and PG secretion during pseudopregnancy, PGF2 alpha alone had no effect on progesterone secretion. These results question the hypothesis that PGF2 alpha alone is the luteolytic factor. PMID- 2917511 TI - Biochemical characterization of the protein affinity labeled by dihydrotestosterone 17 beta-bromoacetate: comparison with the human androgen receptor. AB - Dihydrotestosterone 17 beta-bromoacetate covalently binds to a single protein of 58,000 mol wt from human genital skin fibroblast cytosol. Previous experiments have suggested that this protein is related to the human androgen receptor and may be a proteolytic fragment of the intact protein. In the present study the biochemical properties of the covalently radiolabeled protein were compared to those of the classically defined human androgen receptor radiolabeled noncovalently with [3H]dihydrotestosterone. The radiolabeled proteins were indistinguishable by gel filtration chromatography, sucrose density gradient centrifugation analysis, chromatofocusing, and hydrophobic interaction chromatography. Both ligands labeled a protein with an apparent Stokes radius of 4.4 nm under high salt conditions. Analysis on sucrose density gradients showed peaks of 4.6S and 9.2S with either ligand. The protein radiolabeled with either ligand chromatofocused as two isoforms, a predominant form with a pI of about 5.4 and a minor isoform with a pI of about 4.5. Both radiolabeled proteins were found to have a high degree of hydrophobicity and eluted identically from a phenyl Sepharose column. While the radiolabeled proteins were qualitatively indistinguishable, significantly more radiolabeled protein was quantitated using the affinity ligand. These data suggest that the affinity ligand may recognize precursor or degraded forms of the receptor that do not bind the natural ligand or that assays based on the use of noncovalent ligands could underestimate the receptor content of target cells. PMID- 2917512 TI - Prolactin maintains relaxin and progesterone secretion by aging corpora lutea after hypophysial stalk transection or hypophysectomy in the pig. AB - Porcine corpora lutea persist beyond 150 days in hysterectomized animals compared with about 114 days during normal pregnancy. To explore the mechanism(s) regulating the peak release of relaxin and secretion of progesterone by aging corpora lutea and to examine the direct effect of purified porcine (p) PRL on such corpora lutea, hypophysial stalk transection (HST), hypophysectomy (HYPOX) with or without PRL replacement, and sham operation control (SOC) were conducted on day 110 (estrus = day 0) on purebred Yorkshire gilts that were hysterectomized on days 6-8. The pPRL (0.5 mg every 6 h daily) or PBS (0.5 ml every 6 h daily) was given iv from days 110-120. HYPOX + pPRL, HYPOX + PBS, HST + PBS, and SOC + PBS formed four experimental groups. Peak relaxin concentrations in peripheral plasma (mean values ranged from 22-24 ng/ml) occurred on about day 113 for all groups [113.4 +/- 0.3 days (+/- SE)] regardless of the different surgical interventions. After peak release, relaxin decreased steadily in the HYPOX + PBS group, falling to less than 1.0 ng/ml by 6 days later, whereas relaxin in other groups remained elevated (approximately 7 ng/ml). In the HYPOX plus PBS group, progesterone decreased abruptly, remaining below 1 ng/ml from 1 week onward, lower (P less than 0.01) than that in controls (approximately 19 ng/ml); in the HYPOX + pPRL group, progesterone levels (approximately 17 ng/ml) remained similar (P greater than 0.05) to those in controls (approximately 19 ng/ml) and the HST + PBS group (approximately 15 ng/ml). These results clearly reveal that the pituitary gland plays no direct role in regulating the timed peak release of relaxin from aging corpora lutea in hysterectomized gilts and that the peak release of relaxin on about day 113 is preprogrammed and inherent within such aging luteal cells. This study provides strong evidence that purified pPRL maintains both relaxin and progesterone secretion as well as the morphology of aging corpora lutea for at least 10 days after hypophysectomy in hysterectomized gilts. PMID- 2917513 TI - Aging alters the activity of 5'-deiodinase in the adenohypophysis, thyroid gland, and liver of the male rat. AB - Aging is characterized by a decreased secretion of thyroid hormones in rats associated with unchanged plasma TSH suggestive of impairments in the hypothalamo pituitary-thyroid axis. Since it is known that pituitary T3 is more determinant on TSH secretion than plasma T3, we measured in young (4 months) and old (26 months) male rats the concentration of T3 in the anterior pituitary gland and found that it was similar in young and old animals despite the low circulating levels of thyroid hormones. This was suggestive of age-related differences in the intrapituitary T4 to T3 conversion. We therefore determined the activity of 5' deiodinase (5'-D, type I and type II) in the adenohypophysis and investigated possible age-related changes in this enzyme activity in peripheral tissues by its determination in the thyroid gland and liver (type I) of young and old rats. Intrapituitary 5'-D activity was increased in old compared to young rats (type I 5'-D: 4.59 +/- 0.13 vs. 2.92 +/- 0.33 pmol rT3/h x mg protein; type II: 0.54 +/- 0.5 vs. 0.21 +/- 0.03 pmol rT3/h x mg protein; P less than 0.001). In contrast, in the thyroid gland and in the liver, type I 5'-D was reduced with age (4.7 +/- 0.6 vs. 7.4 +/- 0.8 and 3.1 +/- 0.4 vs. 5.6 +/- 0.5 nmol rT3/h x mg protein, respectively; P less than 0.01). These data are illustrative of age-related changes in the activity of 5'-D, different according to the tissues in agreement with the known tissue-specific regulation of the 5'-Ds. The reduced activity of 5'-D in the thyroid and liver of old rats is indicative of an impaired thyroid hormones disposal in peripheral tissues with age. In contrast, in the adenohypophysis of old rats, the increase in the activity of 5'-D is similar to that reported in hypothyroid animals and suggests the development with age of an adaptative mechanism in the presence of low circulating thyroid hormones; this mechanism leads to unchanged intrapituitary concentration of T3 and consequently to unaltered plasma levels of TSH in old rats. PMID- 2917514 TI - The uptake of [3H]testosterone and its metabolites by the brain and pituitary gland of the fetal macaque. AB - Testosterone is secreted by the fetal testis during gestation, and this is thought to influence certain aspects of the brain's subsequent development. To study this action at the neuronal level, nine macaque fetuses were injected with 250 microCi [3H]testosterone via the umbilical vein at about 120 days gestation. After 60 min, samples of brain and peripheral tissue were studied by autoradiography or HPLC. Purified nuclear pellets were prepared, and radioactivity in ether extracts was fractionated by HPLC and identified by coelution with internal standard steroids. Concentrations of radioactivity were significantly higher (P less than 0.05) in the hypothalamus-preoptic area than in amygdala, hippocampus, midbrain, and cerebral and cerebellar cortexes, and most of the radioactivity (75%) in the hypothalamus-preoptic area coeluted with 17 beta-estradiol. Radioactivity coeluting with 17 beta-estradiol was also detected in nuclear fractions from amygdala (44%). In contrast, 80% of the radioactivity extracted from pituitary gland nuclei coeluted with testosterone. Most of the neurons labeled in autoradiograms were located in the hypothalamus and preoptic area, fewer were found in the amygdala, and labeling in the frontal or motor cortex did not exceed chance levels. Results suggested that aromatization and, consequently, estrogen receptors play a role in the effects of testosterone on the hypothalamus and amygdala of the primate fetus at this stage of development. PMID- 2917515 TI - The hormonogenic sites of turtle thyroglobulin and their homology with those of mammals. AB - Thyroglobulin (Tg) from turtles previously injected with 125I was reduced, alkylated, and digested with trypsin. We purified the resultant peptides on HPLC columns, determined their amino acid sequences and the locations of [125I]T4 and [125I]T3 residues, and compared them with established sequences from humans, cows, rabbits, rats, and guinea pigs. We found five major T4 peptides, three of which were homologous with the major hormonogenic sites A, B, and D of mammalian Tg. Site A, the highly conserved major T4 site in mammals, had substitutions in three residues near the T4 residue and had much less of Tg's newly synthesized T4 than is found in mammalian Tg (25% in turtle vs. 44% in rabbit). Site B contained correspondingly more of Tg's new T4 (42% vs. 24% in rabbit). Turtle Tg contained little [125I]T3, and we did not find site C (Ser-T3/T4-Ser, the major T3 site in guinea pig and rabbit) in turtles, but did find Val-T4, a possible homolog. Site D was quantitatively less important than in mammals. The fifth turtle hormonogenic site, containing 12% of Tg's newly formed T4, had a tyrosyl residue substituted for the phenylalanine at residue 632 in the human sequence. We conclude that Tg's major hormonogenic sites are generally conserved across a considerable evolutionary distance, but that differences in primary structure occur and may contribute to changes in priority of hormone synthesis among these sites. PMID- 2917516 TI - Circulating thyronines and peripheral monodeiodination in lactating rats. AB - The well known metabolic and endocrine adaptive responses accompanying lactation include a change in circulating thyronines that resembles the so-called euthyroid sick syndrome. To analyze the role played by tissue monodeiodination in this state, circulating levels of thyronines as well as hepatic and mammary 5' monodeiodinative activity (5'MA) were assessed during lactation in rats. Results show that the serum iodothyronine changes that accompany lactation are associated with a significant decrease in hepatic 5'MA and a simultaneous increase in mammary 5'MA. These changes begin within the first postpartum day, are proportional to lactation intensity (litter size), and disappear 48 h after either precocious (1st postpartum day) or natural (21st postpartum day) weaning. These data demonstrate that the compartmentalized change in energy expenditure characteristic of lactation is accompanied by organ-specific and opposite adjustments in hepatic and mammary monodeiodinative pathways. PMID- 2917517 TI - Control of gonadotropin secretion in the ovine fetus. II. A sex difference in pulsatile luteinizing hormone secretion after castration. AB - Gonadal involvement in the control of fetal LH secretion was examined by studying LH pulsatility in 12 chronically catheterized male (9 castrate and 3 sham control) and 12 female (8 castrate and 4 sham-control) ovine fetuses operated upon in utero at 106-116 days gestation (term = 147 days). Fetuses were studied longitudinally over a 2- to 30-day period in castrates and over a 2- to 37-day period in controls. 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). In female fetuses there was no significant difference in LH pulse frequency between castrates (25 pulses in 32 periods; 1 pulse/3.8 h of observation) compared to controls (15 pulses in 15 periods; 1 pulse/3.0 h). LH pulse frequency was similar in the sham-castrate males (11 pulses in 17 periods; 1 pulse/4.6 h). In contrast, LH pulse frequency was significantly higher in the castrate male group (90 pulses in 42 periods; 1 pulse/1.4 h) compared to that in each of the other 3 groups (P less than 0.005). LH pulse frequency did not vary with gestational age in castrate and control females or in control males. In castrate males, however, LH pulse frequency declined significantly (P less than 0.005) with advancing gestation from 80 pulses in 32 periods (1 pulse/1.2 h) before 130 days compared to 10 pulses in 10 periods (1 pulse/3.0 h) after 130 days. Thus, LH pulse frequency was indistinguishable in castrate vs. eugonadal males after 130 days. The absence of a castration effect on LH pulsatility in male fetuses older than 130 days was confirmed in an additional group of 8 male fetuses (5 castrate and 3 sham-controls) operated upon at 121-130 days gestation and studied over a 2- to 20-day period. Overall, LH pulse amplitude was similar in male [4.7 +/- 0.5 ng/ml (+/- SE)] and female (3.9 +/- 0.5 ng/ml) fetuses and did not vary as a function of gonadal status or gestational age. The postcastration increment in LH pulse frequency in the castrate male fetus from 108-130 days gestation delineates a role of the fetal testis in feedback regulation of LH secretion at this stage of development. The absence of a postcastration rise in LH pulse frequency in the castrate female indicates that the fetal ovary does not play a similar role.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2917518 TI - An enzyme-linked immunosorbent assay for quantitation of aromatase cytochrome P 450. AB - Traditionally, aromatase has been quantified as aromatase activity according to its ability to produce estrogen from androgen. We have developed a quantitative assay based on the protein mass of catalytically active aromatase cytochrome P 450. A solid phase sandwich enzyme-linked immunosorbent assay for aromatase cytochrome P-450 has been devised using mouse monoclonal antibody (MAb3-2C2) and rabbit polyclonal antiserum (PAb R-8-2). Two rabbit antisera (PAb R-8-1 and R-8 2) were raised by immunization against human placental aromatase cytochrome P-450 which had been isolated by immunoaffinity chromatography of MAb3-2C2-coupled to Sepharose 4B resin. Both antisera were capable of suppressing human placental aromatase activity with IC50 values of 0.6 and 0.8 microliter/ml incubate, respectively, and showed monospecific to aromatase cytochrome P-450 in the Western blot analyses. Solubilized human placental microsomal samples were incubated in microtiter wells precoated with MAb3-2C2. The unbound proteins were washed out, and the aromatase cytochrome P-450 bound with the MAb3-2C2 in the wells was then reacted with PAb R-8-2, the binding of which was subsequently probed with goat antirabbit immunoglobulin G antibody alkaline phosphatase conjugate. Immunoaffinity-purified aromatase cytochrome P-450 of human placental microsomes was used for the standard, with the current assay detection limit at 1 ng/ml. There was a positive correlation between aromatase activity and the immunoreactive aromatase cytochrome P-450 level in solubilized microsomal samples after preincubation at 22 and 37 C, indicating that the enzyme-linked immunosorbent assay measures the level of aromatase cytochrome P-450 that has catalytic activity. The mean level of aromatase cytochrome P-450 in solubilized human term placental microsomes was 16.4 +/- 10.3 (+/- SD) micrograms/ml, corresponding to 0.38 +/- 0.19% of the original microsomes. The mean specific activity of aromatization of the solubilized samples was 0.650 +/- 0.163 nmol estrogen formed/min.mg protein. These results indicate that aromatase in the solubilized placental microsomal fraction has catalytic ability of 5.3 +/- 1.6 min-1 based on the immunoassayable cytochrome P-450. PMID- 2917519 TI - Tumors producing human tumor necrosis factor induced hypercalcemia and osteoclastic bone resorption in nude mice. AB - We used a Chinese hamster ovary cell line that had been transfected with the human tumor necrosis factor (TNF) gene and constitutively produced TNF when transplanted in nude mice to study the effects of continuous production of TNF on calcium homeostasis. Continuous exposure to TNF caused increased osteoclastic bone resorption and humoral hypercalcemia in these animals. The mice bearing TNF producing tumors were significantly hypercalcuric compared to mice bearing control tumors, but urinary cAMP excretion was unchanged. Mice bearing Chinese hamster ovary cell tumors containing the empty vector did not demonstrate hypercalcemia or increased bone resorption. This model system using transfected cells to continuously produce cytokines in vivo is more analogous to the pathophysiological conditions present in patients than intermittent injections and can produce much longer exposures than infusion pumps. Such model systems should allow a better understanding of the role of factors involved in humoral hypercalcemia. PMID- 2917520 TI - Evidence for regulation of peptide-YY release by the proximal gut. AB - Peptide-YY (PYY) is a novel enteric peptide that is structurally related to pancreatic polypeptide and neuropeptide-Y. The objectives of the present experiments were to characterize the following aspects of PYY metabolism: the distribution of PYY in the canine gastrointestinal tract, the release of PYY in response to oral ingestion of a mixed meal or intraduodenal (ID) administration of oleic acid, the effect of ileocolectomy on the release of PYY in response to ID administration of oleic acid when transit of chyme to the distal ileum and colon is prevented, the effect of interruption of intramural neural pathways of the small bowel on the release of PYY, and the effect of iv cholecystokinin on the release of PYY. The results of these experiments demonstrate that PYY immunoreactivity is distributed primarily in the terminal ileum, colon, and rectum. Circulating levels of PYY increase significantly (P less than 0.05) within 10-30 min after ingestion of a meal or to ID administration of a fatty acid. Complete interruption of the flow of chyme to the site of PYY-containing cells (i.e. ileum-colon) did not block the release of PYY; however, ileocolectomy abolished the release of PYY in response to ID administration of oleic acid. Severance of intramural neural pathways along the small bowel did not alter the release of PYY in response to an oral meal. Intravenous administration of graded doses of cholecystokinin stimulated the release of PYY in a dose-related manner. The results of these experiments indicate that the release of PYY from the distal ileum and colon is controlled, at least in part, by an extramural neural, endocrine, or a combination of both types of mechanisms which originate in the foregut. PMID- 2917521 TI - Hypophysectomy of the fetal lamb leads to a fall in the plasma concentration of insulin-like growth factor I (IGF-I), but not IGF-II. AB - The role of the pituitary gland in the regulation of the plasma concentrations of insulin-like growth factors (IGFs) in the late gestation sheep fetus has been examined. Singleton sheep fetuses were either hypophysectomized or sham-operated between days 110-120 of gestation. Blood samples were then collected via carotid cannulae at least three times weekly for the remainder of gestation. In some hypophysectomized fetuses T4 was administered (100 g/day) to overcome the hypothyroidism caused by hypophysectomy. Blood samples were also obtained from lambs during the perinatal period, neonatal lambs within 1-10 days after birth, and pregnant and nonpregnant adult ewes. All plasma samples were subjected to Sephadex G-50 gel filtration under acidic conditions (pH 2.3) to eliminate IGF binding protein activity. The fractions containing the free IGF peptides were collected and assayed for IGF-I by heterologous RIA, and IGF-II by a homologous RRA. Plasma concentrations of IGF-I and IGF-II did not change with advancing gestational age in any fetal group and were not affected by the prolonged gestation that results from hypophysectomy. The mean plasma IGF-I and IGF-II concentrations in the sham fetuses were 112 +/- 8 and 1340 +/- 112 ng/ml, respectively. Hypophysectomy without thyroid hormone replacement resulted in a significant decrease in plasma IGF-I concentrations to 50 +/- 5 ng/ml, whereas IGF-II concentrations were not affected (1096 +/- 124 ng/ml). IGF-I concentrations in the hypophysectomized fetuses that received T4 were significantly increased (67 +/- 6.0 ng/ml) compared to those in the hypophysectomized fetuses that did not receive T4. The IGF-II concentrations in the hypophysectomized fetuses that received T4 were similar to those in the sham operated fetuses (1120 +/- 112 ng/ml). At term IGF-I concentrations were increased (180 +/- 21 ng/ml) and IGF-II concentrations were decreased (264 +/- 25 ng/ml) compared to fetal values. Plasma IGF-I concentrations in the prepubertal lamb were similar to the fetal values. Pregnancy in the adult ewe was associated with a significant increase in IGF-II, but had no effect on IGF-I plasma concentrations. These data show that circulating IGF-I concentrations in the fetal lamb are under some pituitary and thyroid control, whereas IGF-II concentrations are independently of pituitary or thyroid status. We confirm, using a homologous assay, that fetal IGF-II concentrations are high and then decrease at term. These data also support the concept that a pregnancy-related factor may regulate plasma IGF-II concentrations.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2917522 TI - Platelet-activating factor stimulates prolactin release from dispersed rat anterior pituitary cells in vitro. AB - The biologically active phospholipid (platelet-activating factor (PAF; 1-O-alkyl 2-acetyl-sn-glycero-3-phosphocholine) stimulated PRL release from dispersed rat anterior pituitary cells in culture. PAF-induced PRL release was dose dependent, with threshold stimulation at 1 nM and maximal stimulation at 100 nM. Stimulation occurred as early as 1 min of incubation and persisted for 2 h. The action of PAF on PRL release is consistent with a receptor-mediated mechanism based on the observations that the action of PAF is blocked by dopamine agonists and the PAF receptor antagonists L 652731 and SRI 63072. The structural analogs 1-O-alkyl-2 oleoyl-sn-glycero-3-phosphocholine and 1-O-alkyl-2-acetyl-sn-glycero-3 phosphoethanolamine, which lack the biological activity of PAF, are not able to stimulate PRL release over the dose range 0.2-2 microM. In addition, the PAF precursor lyso PAF and diacyl-sn-glycero-3-phosphocholine (phosphatidylcholine) were ineffective in stimulating PRL release. PAF induced the secretion of PRL and GH but not that of LH or TSH from hemipituitaries in short term incubations. PAF did not effect PRL release from GH3 cells. In conclusion, these data indicate that PAF stimulates PRL release from primary cultures of rat anterior pituitary cells in a dose-related, rapid, and specific manner. PMID- 2917523 TI - Mammotroph autoregulation: the differential roles of the 24K isoforms of prolactin. AB - In this study we have attempted to determine which of the secreted 24K isoforms was responsible for autocrine regulation of PRL secretion by comparing the isoforms synthesized and secreted by normal cells, which do autoregulate, with those synthesized and secreted by GH3 cells, which do not normally autoregulate. Comparable numbers of cells were washed free of serum and then extracted into Tris-buffered saline by sonication and detergent treatment. Proteins present in these cell extracts and in samples of culture medium were then precipitated with cold acetone (-20 C; 48 h) and subsequently dissolved in urea-lysis buffer for 2 dimensional (2-D) electrophoresis. The 2-D patterns for normal cells showed four 24K PRL isoforms inside the cells and three 24K PRL isoforms (designated 2, 3, and 3') secreted into the medium. The 2-D patterns for GH3 cells showed very little intracellular storage of PRL, but what was present was identified as 24K PRL isoform 2. The GH3 cells secreted large amounts of only 24K PRL isoform 2. Preparations of PRL containing only isoforms 1,2, and 3 (at a total radioimmunoassayable concentration of 5 micrograms/ml PRL) were capable of inducing autoregulation in GH3 cells, as evidence by decreased secretion of prelabeled intracellular PRL. Initiation of autoregulation in GH3 cells caused granulation and the intracellular production of isoform 3. Since a) a preparation containing isoforms 1, 2, and 3 was found to induce autoregulation in GH3 cells, b) isoform 1 is not a secreted form, and c) isoform 2 does not cause autoregulation (at least in GH3 cells), it is deduced that isoform 3 is an autocrine form of PRL. Since initiation of autoregulation in GH3 cells caused those cells to produce isoform 3, it is further deduced that the autoregulatory defect in GH3 cells lies in the actual lack of production of isoform 3 and not in an inherent inability of these cells to produce isoform 3. PMID- 2917524 TI - Two forms of glycosylated human prolactin have different pigeon crop sac stimulating activities. AB - Two forms of glycosylated PRL (G-PRL) which differed in their binding properties to Concanavalin-A (Con-A) were isolated from human pituitary glands. One form, G1 hPRL, was only slightly retarded by Con-A; the other, G2-hPRL, was adsorbed by Con-A and could be eluted with methyl-D-manno-pyranoside, an indication of differing carbohydrate units in the two G-PRLs. Differences in type of glycosylation were also indicated by HPLC peptide mapping of tryptic digests of the two forms. The elution time for the tryptic peptide carrying the asparagine linked carbohydrate unit varied for the two G-PRLs. The results point to the asparagine at position 31 as being the site of attachment of the carbohydrate. The carbohydrate structure influenced the crop sac-stimulating activity of the G hPRLs. G1-hPRL had only about one fourth the activity of the reference standard (nonglycosylated ovine PRL, 35 IU/mg). The form that bound to Con-A, G2-hPRL, was equipotent to the reference standard. Because glycosylated forms have varying biological activities and are major components of circulating PRL, the physiological significance of serum concentrations of PRL measured by RIA will have to be reevaluated. PMID- 2917525 TI - The effects of prolactin and prostaglandin F2 alpha on plasma membrane changes during luteolysis in the rat. AB - The ability of PRL to modify prostaglandin F2 alpha (PGF2 alpha)-induced membrane changes during functional corpus luteum regression was examined in the pseudopregnant rat. Fluorescence polarization studies conducted 24 h after sc injection of PGF2 alpha revealed a marked and significant increase in the polarization parameter, which is suggestive of reduced plasma membrane fluidity. At the same time, there was a decrease in hCG binding and a significant increase in apparent phospholipase-A2 activity during incubation of dispersed rat luteal cells. Each of these changes was attenuated when the animals were pretreated with PRL 30 min before PGF2 alpha. The decrease in plasma progesterone caused by PGF2 alpha treatment was also inhibited by PRL. PGF2 alpha also stimulated a significant polarization increase in dispersed cells prepared from ovaries removed 1 h after injection of this luteolytic agent, although this effect could not be demonstrated in plasma membrane samples. These results indicate that PRL and PGF2 alpha affect the same membrane pathway in the rat corpus luteum and that this pathway appears to be closely coupled to luteal cell function. PMID- 2917526 TI - Extracellular calcium modulates vitamin D-dependent calbindin-D28K gene expression in chick kidney cells. AB - The effect of extracellular calcium ion (Ca2+) concentration on 1,25 dihydroxyvitamin D3 (1,25-(OH)2D3)-induction of vitamin D-dependent calcium binding protein (calbindin-D28K) and its mRNA levels was examined in primary chick kidney cells in vitro. When exposed to normal medium Ca2+ (1.0 mM), 1,25 (OH)2D3 increased calbindin-D28K mRNA, as measured by Northern analysis, by 4-10 fold over basal levels by 12 to 24 h after addition of hormone. In the presence of 0.5 mM Ca2+, 1,25-(OH)2D3 induced calbindin-D28K mRNA by only 2 fold, whereas, when cells were exposed to 2 mM Ca2+, the induction was 10-15 fold. This calcium modulation of 1,25-(OH)2D3 induction was also observed at the level of calbindin D28K protein concentrations as measured by radioimmunoassay. The alterations in medium Ca2+ were not associated with any change in the rate of total RNA or protein synthesis. These studies suggest that both Ca2+ and 1,25-(OH)2D3 participate in the regulation of calbindin-D28K gene expression in the kidney. PMID- 2917527 TI - Diurnal rhythm of melatonin binding in the rat suprachiasmatic nucleus. AB - We used quantitative in vitro autoradiography to localize and characterize 2-125I melatonin binding sites in the rat suprachiasmatic nuclei in relation to pineal melatonin production. In a light:dark cycle of 12:12 h, binding density exhibited significant diurnal variation with a peak at the dark-light transition and a trough 12 hours later. Saturation studies suggested that the decreased binding at light-dark transition might be due to a shift of the putative melatonin receptor to a low affinity state. PMID- 2917528 TI - The antinatriuretic and kaliuretic effects of the glucocorticoids corticosterone and cortisol following pretreatment with carbenoxolone sodium (a liquorice derivative) in the adrenalectomized rat. AB - Carbenoxolone Sodium (CS), a chemical derivative of liquorice is known to be associated with hypertension, increased sodium retention and hypokalemia. The present studies describe the effects of CS on the renal actions of the glucocorticoids Corticosterone (B) and Cortisol (F) on sodium and potassium in adrenalectomized male rats. B (50, 100 and 500 micrograms/rat) and F (1 mg/rat) were found to possess no intrinsic antinatriuretic activity which is represented by a decrease in the Na+ to creatinine ratio; while only B (500 micrograms/rat) demonstrated kaliuretic effects as indicated by an increase in K+ to creatinine ratios. B and F showed very significant antinatriuretic and kaliuretic properties following pretreatment with CS (2.5 mg/rat). CS alone was not found to be antinatriuretic at this dosage. Further experiments demonstrated that lower dosages of CS (500 and 1,000 micrograms/rat) also cause B to exhibit Na+ retaining and K+ excreting properties. Thus, we have demonstrated that pretreatment with CS can confer mineralocorticoid-like activity upon the glucocorticoids B and F. PMID- 2917529 TI - Endoscopic diagnosis of reflux esophagitis by the dye-spraying method. AB - Twenty-one patients (13 patients after gastric surgery and 8 patients with hiatus hernia or other esophageal disease) in whom reflux esophagitis had been diagnosed by standard endoscopy, and who had undergone Lugol-spraying endoscopy, were reviewed. Ninety-two biopsy specimens were obtained from the esophageal mucosa under direct vision and stained with hematoxylineosin and PAS. The coincidence rate of the findings of dye-spraying endoscopy with histological findings was 89.9% (80/89), as opposed to 69.7% (62/89) attained by standard endoscopy (p less than 0.001), indicating that Lugol-spraying endoscopy is highly compatible with histology. Of 34 biopsy specimens showing papillary hyperplasia, 18 (52.9%) were stained unevenly and lightly, and 14 (41.2%) evenly and lightly. Of nine biopsy specimens showing epithelial regeneration, eight (88.9%) were unstained. All 26 biopsy specimens with erosion/ulcer were also unstained. It is concluded that Lugol-spraying endoscopy is of value in diagnosing reflux esophagitis, especially in determining the intensity and extent of the disease. PMID- 2917530 TI - Endoscopic balloon hydrodilatation and endoprosthetic treatment of esophageal and esophageal anastomotic strictures. AB - In 37 patients with benign stenosis of the esophagus and esophageal anastomoses, the method of dilatation using special balloon catheters under endoscopic control was employed, and adequate dilatation of the stenotic region accomplished. In comparison with balloon dilators, bougies exert forces along the radial axis, and no tension is applied to the esophagus along the longitudinal axis. To obtain prolonged remission and decrease the number of "supporting" dilatations of esophageal benign stenosis and esophageal anastomoses, temporary intubation of the esophagus with a silicone prosthesis was performed in 7 patients. Further clinical application, and a study of the long-term results of endoscopic balloon hydro-dilatation and endoprosthesis for treating esophageal and anastomotic esophageal strictures, will help to elaborate more precise indications for the combined use of these methods. PMID- 2917531 TI - Biliary lithiasis: combined endoscopic and surgical treatment. AB - A combined endoscopic and surgical procedure was performed in 69 patients suffering from gallbladder lithiasis with suspected associated lithiasis of the common bile duct (CBD). The procedure was spread over two days: Day 1 - Endoscopic retrograde cholangiopancreatography (ERCP) revealed choledocholithiasis in 50 cases and papillary sclerosis in 4 cases. In 15 patients, the common bile duct was found to be normal. Fifty-four endoscopic sphincterotomies were performed. Among the 50 cases of choledocholithiasis, endoscopic removal of the stones was judged complete in 44 cases and incomplete in the other 6. Day 2 - Cholecystectomy was carried out in all the patients. Peroperative cholangiography confirmed the results of the pre-operative ERCP with respect to the CBD in all the patients except one, and a choledochotomy was necessary in 6 patients. Results were as follows: The average length of hospitalization was 12.4 days. No residual choledocholithiasis was noted. The morbidity of the procedure was 7.2%, and the mortality 1.4% unrelated to the technique. The diagnostic and therapeutic significance of the procedure is discussed. PMID- 2917532 TI - Does the endoscope control head need to be disinfected between examinations? AB - An evaluation was made of the incidence of contamination of endoscope control heads during gastroduodenoscopy and colonoscopy, and of the efficacy of a simple disinfection technique. Contamination of the control heads occurred in 4 out of 17 examinations. Scrubbing in detergent followed by wiping with swabs impregnated with 70% isopropyl alcohol and 2% chlorhexidine achieved adequate disinfection of artificial heavy contamination of the control head. The endoscope control head represents a potential source of cross-infection and should not be neglected in any cleaning procedure. PMID- 2917533 TI - Endoscopic pancreatic sphincterotomy--technique and evaluation. AB - Endoscopic pancreatic sphincterotomy has been developed as a new method of treatment of chronic pancreatitis in our institution since 1982. We introduced pancreatic sphincterotomy as a safe technique, after performing it successfully in 21 cases of chronic pancreatitis without any complications, and relieving both abdominal and back pain in 19 of the cases. Recently, we have added endoscopic elimination of viscid pancreatic juice including protein plugs. This report describes our procedure of pancreatic sphincterotomy in detail, and evaluates it in the endoscopic treatment of chronic pancreatitis. PMID- 2917534 TI - A comparative study of the tissue-destroying effect of the laser and electrocoagulation. AB - The effect of the laser on compact, glandular tissue at the dosage employed for the local palliative treatment of tumors, can largely be mimicked with the aid of high-frequency current (HF-current), applied with the aid of an electro-hydro thermo-probe: The experiments described in the present study were performed on the livers of 70 male Wistar rats. The laser was applied for 2 seconds at an output of 80 J at a distance to the tissue of 0.5 cm. In the first stage, in the acute experiment, the effect of the HF-current was matched to that of the laser by varying the modulated and unmodulated current components. It was found that the depths of penetration into the tissue at the given laser settings could be achieved with modulated HF-current (so-called coagulation current) at an output of more than 72 watts (equipment setting K 10) coagulation being performed for 10 seconds. The admixture of modulated HF-current (so-called cutting current) reduces the depth of penetration into the tissue. In the first 5 days, the depth of penetration increases after both laser irradiation and HF-coagulation, by a factor of 2 to 3. With respect to the depths of penetration (DP), the scatter ranges, and the histological changes, no difference is to be seen between laser and HF lesions: Laser DP = 5.7 mm (confidence range: 4.4-7.0 mm); HF DP (equipment setting K 10) = 4.8 mm (confidence range: 3.6-5.4 mm).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2917535 TI - Brunner's gland hamartoma associated with microcarcinoids. AB - We report on the case of a 51-year-old female with a pedunculated duodenal tumor that was covered with normal duodenal mucosa. Histology of the endoscopically resected tumor revealed Brunner's gland adenoma with two foci of microcarcinoids. To our knowledge, such a case has not been reported in the literature. PMID- 2917536 TI - Five cases of ectopic liver and a case of accessory lobe of the liver. AB - Five cases of ectopic liver, two of retro-peritoneal cavity and three of gallbladder, and a case of accessory lobe of the liver, are reported. One of these cases with ectopic liver was accompanied by multiple cysts of the liver and kidney, and biliary microhamartoma, which was observed laparoscopically on the surface of the main liver and histologically proven in the ectopic liver. PMID- 2917537 TI - Acute renal failure after endoscopic injection sclerotherapy: a report of two cases. PMID- 2917538 TI - Acute appendicitis following endoscopic polypectomy. PMID- 2917539 TI - Successful endoscopic treatment of GI-tract fistulas with a fast-hardening amino acid solution. PMID- 2917540 TI - Anaphylactic reaction to ethanolamine oleate injection in sclerotherapy of esophageal varices. PMID- 2917541 TI - Hepatic abscesses and "sump syndrome": a new case. PMID- 2917542 TI - Through-the-scope balloon dilatation of benign pyloric stenoses. AB - In 9 patients with benign pyloric stenosis, the stenosis was dilated using through-the-scope (TTS) balloon catheters (diameter 1.5 to 1.8 cm), which can be passed through the biopsy channel of a standard fiberscope under direct vision. In all cases, the stenosis was secondary to fibrous changes in peptic ulcer disease. In addition, all patients had active ulcers. All dilatation treatments were primarily successful: the stenoses were opened for the passage of the fiberscope. There were no complications; even with active ulcers there were no side effects. The treatment was followed by immediate symptomatic relief. On prospective evaluation over a period of 7 months (mean), 6 patients remained asymptomatic, 2 patients had to be dilated again for restenosis and have since been asymptomatic for 1 and 12 months, respectively. One patient had to undergo surgery after 7 months for ulcer perforation into the common bile duct. The TTS technique has considerable advantages over the methods requiring a guide wire. This technique with its easy practicability and low incidence of complications may become a valid alternative to surgical procedures if the good initial results can be confirmed in further studies. PMID- 2917543 TI - Response of rat alveolar macrophages to ozone: quantitative assessment of population size, morphology, and proliferation following acute exposure. AB - The purpose of this study was to evaluate the in vivo effects of an acute exposure to low levels of ozone on rat pulmonary alveolar macrophages (PAM). Fisher 344 rats exposed to 0.0, 0.12, 0.8, or 1.5 ppm O3 for 6 h were killed immediately after and 3, 18, 42, or 66 h after ozone exposure and their lungs were lavaged. Compared to sham-exposed (control) rats, exposure to 0.12 ppm O3 had no measurable effect on the total number, labeling index (LI), mitotic index (MI), or morphology of rat alveolar macrophages. The number of neutrophils was significantly (p less than or equal to 0.001) greater than in controls at 3, 18, and 42 h after exposure to 1.5 ppm O3 and 42 h after exposure to 0.8 ppm O3. The number of PAM was approximately twice that of controls 42 and 66 h after exposure to 0.8 and 1.5 ppm O3. There was a significant (p less than or equal to 0.001) increase in PAM MI 42 and 66 h after exposure to 1.5 ppm O3 and 42 h after 0.8 ppm O3. The increase in the number of PAM in mitosis was preceded by an increase in PAM LI. The PAM LI was significantly (p less than or equal to 0.001) greater than controls 18 and 42 h after exposure but returned to near normal levels by 66 h after exposure. There was a transient decrease in the mean nuclear/cytoplasmic ratio of PAM from rats exposed to 1.5 ppm O3 18 and 42 h after exposure due to an increase in the mean PAM cytoplasmic area. Comparison of the PAM population doubling time (Dt) and cell cycle time (Ct) suggest that PAM proliferation played a significant role in the observed increase in PAM following exposure to 0.8 and 1.5 ppm O3. These results highlight the dynamic response of PAM to an acute exposure to ozone and suggest that the proliferative response of pulmonary alveolar macrophages may be a useful indicator of pulmonary damage following inhalation of an irritant oxidant. PMID- 2917544 TI - Induction of the stress response by isolation of rabbit type II pneumocytes. AB - Protein synthesis by isolated rabbit type II pneumocytes was evaluated by incorporation of labeled amino acids, gel electrophoresis, and fluorography. Type II alveolar epithelial cells preferentially synthesize a small number of proteins immediately following isolation and simultaneously exhibit a depression of all other protein synthesis. Examination of the time course of the appearance and decline of these proteins showed them to be actively synthesized during the first 14 h after isolation. Decline in their production was accompanied by a gradual enhancement in the synthesis of other proteins. Actin synthesis was not measurable 1 h after isolation, but increased to 9% of total label incorporated by 14 h. This recovery was independent of attachment to an extracellular matrix. Treatment with actinomycin D immediately following cell isolation abolished the synthesis of these proteins, suggesting a requirement for active mRNA production. A subset of these proteins are induced by heat treatment of cultured type II cells. The half-life, intracellular localization, isoelectric points, apparent molecular weights, and heat inducibility of this group of proteins are similar to stress proteins found in other mammalian systems. These stress proteins are unique in that their synthesis is induced by the cell isolation process. Possible mechanisms by which cell isolation may induce the stress response are discussed. PMID- 2917545 TI - Recovery of decreased glutamate decarboxylase immunoreactivity after rat hippocampal kindling. AB - The present study was designed to test the hypothesis that chronic gamma aminobutyric acid (GABA) disinhibition of granule cells could explain permanent kindled epileptogenicity. Quantitative and statistical comparisons of glutamate decarboxylase immunoreactivity (GAD-IR), the synthesizing enzyme for GABA, were made of GAD-IR cells and puncta in stratum granulosum of the fascia dentata. The use of GAD immunocytochemistry in kindled and control tissue was used to allow direct anatomic confirmation that we were measuring changes in GAD-IR which would represent GABA synthesis for release by the recurrent inhibitory system of the fascia dentata. Immediately after the last kindled seizure, optically detected GAD-IR puncta densities were significantly reduced in stratum granulosum. At 3 or 7 days after the last kindled seizure, GAD-IR was normal in puncta, indicating that the transient GAD-IR loss was probably a metabolic response to the recent seizure represented by over-use of GAD needed for synthesis of GABA after a prolonged kindled seizure. When the prolonged kindled seizures were discontinued GAD-IR recovered in the puncta. This transient effect did not occur in other areas such as Ammon's horn (CA3) or substantia nigra. The extent of the GAD-IR loss showed no correlation with the severity of the final behavioral seizure (R = 0.23), or the final afterdischarge (AD) duration in entorhinal cortex (R = 0.17) or motor cortex (R = 0.53). A massed stimulation control group given 19 shorter duration ADs every 10 min (non-kindling) did not reduce GAD-IR. These findings support the hypothetical model that prolonged kindled seizures release excessive GABA which depletes GAD in axon terminals for 1 day after the seizure. However, such a transient suppression of GAD-IR provides no evidence that disinhibition contributes to the kindling process, because kindling proceeds normally with inter-seizure intervals as long as 1 week. The finding of full recovery of GAD-IR within 1 week does not support the model of loss of GABA inhibition to explain the permanency of kindled epileptogenesis. PMID- 2917546 TI - A comparison of the anticonvulsant effects of 1,4- and 1,5-benzodiazepines in the amygdala-kindled rat and their effects on motor function. AB - Studies suggest that the 1,5-benzodiazepine clobazam possesses a favorable anticonvulsant profile due to its minimal neurotoxicity. The anticonvulsant and motor impairment effects of clobazam and 2 1,4-benzodiazepine, diazepam and clonazepam, were compared by dose-response analysis in amygdala-kindled rats and on 3 tests of motor function: gross motor impairment, a vertical screen test, and muscle tone. All drugs produced a significant, dose-dependent decrease in the duration of both behavioral and electrographic kindled seizure measures. Forelimb clonus suppression was the most sensitive measure of anticonvulsant drug effect. The order of potency for all effects was clonazepam greater than diazepam greater than clobazam. ED50s for the benzodiazepines' effects on motor impairment were compared to their ability to protect rats from forelimb clonus. Different spectrums of action for the various benzodiazepines were found depending on the comparison measure. Clonazepam had the most favorable ratio of potency for anticonvulsant vs. motor impairment activity when ataxia rating was the comparison measure. Diazepam had the most advantageous profile when the more sensitive screen test was used for comparison. Clobazam was not found to have a superior spectrum of action when compared across these measures. The results emphasize the importance of dose-response analyses and the consideration of behavioral measures used to assess beneficial and adverse effects of anticonvulsants. PMID- 2917547 TI - Hypothesis: the classification of epileptic seizures according to systems of the CNS. AB - Several comprehensive classifications of the epilepsies and epileptic syndromes have been proposed and the purpose of the last one (1985) was to supplement the International Classification of Epileptic Seizures as accepted by the General Assembly of the International League Against Epilepsy in 1981. These efforts represent a major contribution to a difficult problem, which must be continued as further scientific advances permit. Categorization according to clinical seizure type is a logical approach, inasmuch as response to antiepileptic medication depends more on seizure type than on etiological or other factors. A limitation of this approach, however, has arisen as a result of the Commission's failure to relate clinical seizure types to the underlying neurophysiology that mediates them. This has resulted in the categorization of absence as a generalized form of seizure along with generalized tonic-clonic seizures (GTCS). On the other hand, temporal lobe seizures (including automatisms) have been categorized as a complex form of partial seizures, which emphasizes their focal origin. It is the belief of the authors that a further clarification might be achieved, if a differentiation of seizure types is made with respect to the underlying CNS circuitry which mediates the sustained discharge that determines the clinical manifestations of each type. Focal origins, while significant, assume a secondary importance, since they do not explain the sustained discharge that mediates clinical seizure types, except in the case of elementary partial seizures (EPS) that remain discretely localized. In contradistinction to GTCS that essentially involve the entire CNS, absence and complex partial seizures (CPS) should be categorized as limited forms of seizures, mediated by bilateral, regional systems.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2917548 TI - Human brain phenytoin: correlation with unbound and total serum concentrations. AB - Simultaneous brain (gray matter) and serum specimens from 18 patients treated with oral phenytoin, who underwent cortical resections for intractable seizures, were analyzed by HPLC. The correlation between brain phenytoin concentration and unbound (free) phenytoin (r = 0.98-0.99) was significantly better than the correlation between brain phenytoin and total serum phenytoin (r = 0.90-0.93). Phenytoin concentrations in tissue from epileptic foci were slightly lower than brain phenytoin concentrations in non-epileptic regions in the same patient (means 15.0 vs. 15.5 micrograms/g, P less than 0.05). The results support the value of monitoring unbound phenytoin in clinical situations where phenytoin binding is highly variable. PMID- 2917549 TI - Hypoglycemia. PMID- 2917550 TI - Micronuclei formation in somatic cells of mice exposed to 50-Hz electric fields. AB - Male Swiss mice are tested under uniform 50-Hz electric field intensities of 100, 170, 220, and 290 kV/m. These values on the basis of equal induced current density are equivalent to the case of a human exposed to field intensities of nearly 8, 14, 18, and 24 kV/m, respectively. The latter values may be found beneath or in the vicinity of extra-high-voltage power lines whose voltages range from 220 to 765 kV. The cytogenetic effect of extremely low-frequency (ELF) electric fields, as expressed by micronuclei formation, is assessed. Mice are exposed for 24 hr, and samples are taken 48, 72, and 96 hr from the beginning of exposure. Sham-exposed mice served as controls. The number of micronucleated polychromatic erythrocytes (PCE) in exposed animals are significantly higher than those of the control. The increase in micronucleated PCE was significantly dose dependent at all times. Samples taken 96 hr after exposure show a decrease in percentages of micronucleated PCE, which may be taken as an indication of recovery. PMID- 2917551 TI - Absence of cinoxacin-induced DNA fragmentation and mutations in the rat granuloma pouch. AB - The mutagenic and DNA-damaging activities of cinoxacin were evaluated in the rat granuloma pouch assay (GPA) in order to assess its genotoxic potential in vivo. High doses of this antimicrobial quinolone, either directly injected into the pouch or administered by gavage, did not induce mutation at the hgprt locus or DNA fragmentation in granuloma cells. Moreover, DNA damage was absent in the liver and kidney of rats given cinoxacin by the oral route. PMID- 2917552 TI - Chromosome aberration and sister chromatid exchange tests in Chinese hamster ovary cells in vitro. III. Results with 27 chemicals. AB - Twenty-seven chemicals previously tested in rodent carcinogenicity assays were tested for induction of chromosomal aberrations (ABS) and sister chromatid exchanges (SCE) in Chinese hamster ovary (CHO) cells as part of a larger analysis of the correlation between results of in vitro genetic toxicity assays and carcinogenicity bioassays. Chemicals were tested up to toxic doses with and without exogenous metabolic activation. Seventeen of the chemicals tested were carcinogens; only two of these were negative for both ABS and SCE. Of the eight noncarcinogens tested, four were negative for both endpoints (ABS and SCE) and four gave a positive response for at least one endpoint. Of the remaining two chemicals, one, diallyl phthalate, gave an equivocal response in the bioassay and a positive response in these CHO cell cytogenetics tests. The other chemical, 2,4 toluene diisocyanate, was tested for carcinogenicity as a mixture with the 2,6 isomer; the mixture was carcinogenic, but the cytogenetic test results for the 2,4-isomer were negative. Only six of the 27 chemicals tested produced an effect in one endpoint alone; the other 21 were either positive or negative for both ABS and SCE. Only one of the 27 chemicals tested required S9 for a positive response in the SCE test; two chemicals required S9 for a positive result in the ABS test. Experiments with unsynchronized CHO cells demonstrated that mean SCE frequency increased with increasing culture time, and this may have been a factor in the positive results obtained for five chemicals in the SCE test under conditions of delayed harvest. PMID- 2917553 TI - Factors involved in preferential transcription of the fibroin gene. AB - Transcription factors for class II genes from a tissue source, the posterior silk glands of Bombyx mori, were fractionated by stepwise elution on a phosphocellulose column into five fractions: A (0.04 M KCl flow through), A' (0.1 M KCl eluate), B (0.3 M KCl eluate), C (0.5 M KCl eluate) and D (1 M KCl eluate). The minimal requirement for reconstruction of accurate initiation of transcription of the fibroin gene, as well as of the adenovirus 2 major late promoter, was the combination of fractions A, B and D, suggesting that transcription factors from B. mori can recognize general signals of the promoters for class II genes and that basic transcription factors are conserved even in distantly diverged species of eukaryotes. To detect activities stimulating the transcription governed by the promoter of fibroin gene, each fraction was tested for its function by supplementing a basal amount of HeLa cell extract. When circular templates were used, stimulatory activities specific for the fibroin gene were detected in fraction D. This preferential transcription is composed of at least three activities; the first and the second dependent on the upstream elements and the third dependent on the sequence downstream from the TATA box. However, when linear templates were used the preference for the fibroin gene was apparently lost and transcription activation by fraction D became general. PMID- 2917554 TI - Molecular differences between rat-liver and rat-kidney biliverdin reductase. Implications for their in vivo regulation. AB - Rat-liver biliverdin reductase exists in two molecular forms. The major form 1 has a molecular mass of 34 kDa, while the minor form 2 has a molecular mass of 56 kDa. Form 1 was converted into a second major form (form 3) with a molecular mass of 68 kDa by a NAD+-dependent peroxisomal dehydrogenase which was induced under conditions of oxidative stress [Frydman, R. B., Tomaro, M. L., Awruch, J. & Frydman, B. (1984) Biochem. Biophys. Res. Commun. 121, 249]. Molecular form 1 from rat kidney was not affected by the dehydrogenase, and a structural explanation for this difference was therefore sought. Both form 1 biliverdin reductases, isolated from rat liver and kidney, were purified to homogeneity using affinity chromatography, FPLC and HPLC techniques. The homogeneous enzymes were found to be identical when compared by their HPLC retention times, amino acid compositions and electrophoretic behaviour on polyacrylamide gels under non denaturing conditions and on SDS/polyacrylamide gels. On HPLC analysis the peptides resulting from the CNBr cleavage were found to be the same for both enzymes, when either the native enzymes or their thioethylpyridine derivatives were compared. When the HPLC fingerprints of the tryptic digests were compared, they were found to be very similar, except for a peptide eluting at 31.60 min in the liver digest and at 23.60 min in the kidney digest. When the enzyme from both origins was alkylated with 4-dimethylaminoazobenzene-4'-iodoacetamide and then digested with trypsin, the HPLC fingerprints of the alkylated cysteine-carrying peptides were almost identical, except for a peptide with a retention time of 19.03 min in the liver digest and of 18.19 min in the kidney digest. The liver reductase was not amenable to Edman degradation suggesting a block at the NH2 terminus; in the kidney enzyme, however, it was free and an NH2-terminal sequence of 12 amino acids could be determined. The liver enzyme was found to be more sensitive toward p-hydroxymercuriphenyl sulfonate than the kidney enzyme. PMID- 2917555 TI - Specific antibodies reveal ordered and cell-cycle-related use of histone-H4 acetylation sites in mammalian cells. AB - Antibodies specific for the acetylated forms of histone H4 (H4) were produced in rabbits with a synthetic peptide corresponding to the 18 N-terminal residues of tetra-acetylated H4 (i.e. with acetyllysine at positions 5, 8, 12 and 16). Specificity was determined by inhibition assays using four additional peptides, each acetylated at only a single site. Using an antiserum (R6) specific for the acetylation site at Lys-5 we have estimated the proportion of Lys-5 sites acetylated in the mono-, di- and tri-acetylated forms of H4 from randomly growing human HL-60 cells. The values obtained (7%, 29% and 61% respectively) differ from those expected if acetylation were random (i.e. 25%, 50% and 75%) or if site usage followed a set order for all H4 molecules (i.e. a jump from 0% to 100%). Antibodies from a second animal (R5) bound preferentially to peptides acetylated at Lys-12 and also bound to mono-acetylated H4 relatively weakly in several cell types. In contrast, mono-acetylated H4 from metaphase HeLa cells labelled more strongly with both antisera, indicating significant acetylation at Lys-5 and Lys 12. We conclude that (1) the sites at Lys-5 and Lys-12 are under-used in mono acetylated H4 from a variety of mammalian cell types and Lys-8 and/or Lys-16 are therefore the first to be acetylated, (2) more than one order of site usage is possible and (3) there is a metaphase-specific shift in site usage. These results suggest that H4 acetylation plays a role in the modulation of chromatin structure in mammalian cells. PMID- 2917556 TI - Characterization of the S'-subsite specificity of porcine pancreatic elastase. AB - A number of maleyl peptide p-nitrobenzyl esters have been synthesized to study elastase-catalyzed hydrolysis reactions. These new substrates were used as acyl donors to investigate the S'-subsite specificity of porcine pancreatic elastase by partitioning of the acyl enzyme between various added nucleophiles and water. The following results were obtained. 1. Porcine pancreatic elastase prefers amino acid residues with small side chains in the P'1 position. 2. The nucleophile binding is improved by a positively charged P'1 side chain, whereas a negatively charged function results in a very low binding tendency. 3. Elongation of the nucleophile to the P'2 position leads to higher aminolysis rates. 4. S' specificity is substantially influenced by the P1 residue of the acyl enzyme. PMID- 2917557 TI - Implication of the alpha 1 beta 1 interface in the hemoglobin affinity changes. A comparative study between normal and San Diego fully ligated hemoglobins. AB - The alpha 1 beta 1 interface of normal and mutated San Diego hemoglobins in their fully liganded form was investigated, through the SH vibrational absorption of beta-112 cysteine, by Fourier-transform infrared spectroscopy. The center frequency of this thiol group was significantly shifted in San Diego hemoglobin compared with normal human hemoglobin. Different dimer organization between the two proteins was also revealed by circular dichroism of the heme. These findings agree well with assessment that the alpha 1 beta 1 interface, far from being inert, is involved in the affinity changes of the hemoglobin molecule. PMID- 2917558 TI - Inhibition of mammalian spermine synthase by N-alkylated-1,3-diaminopropane derivatives in vitro and in cultured rat hepatoma cells. AB - A number of N-alkylated-1,3-diaminopropane derivatives [H2N-(CH2)3-NH-(CH2)nH, where n = 1-9] have been tested as potential inhibitors of partially purified rat hepatoma (HTC) cell or pure bovine spleen spermine synthase. Among the compounds described in this paper, the most potent competitive inhibitor of spermine synthase, with respect to spermidine, is N-butyl-1,3-diaminopropane with Ki values of 11.9 nM and 10.4 nM for the HTC cell and bovine spleen enzymes respectively. Inhibition of spermine synthase by this alkylated amine is selective since spermidine synthase activity is not affected up to 100 microM N butyl-1,3-diaminopropane at a range of 5-200 microM putrescine. Added to the culture medium of growing HTC cells, N-butyl-1,3-diaminopropane causes the expected changes in the polyamine levels with a marked decrease of spermine and an increase of spermidine. Under these conditions cell growth continues unabated. Such N-alkylated-1,3-diaminopropane derivatives may have considerable potential as tools for studying the role of polyamines and in particular the functions of spermine in cell multiplication and differentiation. PMID- 2917560 TI - A protein from rat liver confers to glucokinase the property of being antagonistically regulated by fructose 6-phosphate and fructose 1-phosphate. AB - At a concentration of 1 mM, fructose 1-phosphate stimulated about twofold, and glucose 6-phosphate inhibited by about 30%, the phosphorylation of 5 mM glucose in high-speed supernatants prepared from rat liver or from isolated hepatocytes, but did not affect, or barely so, the activity of a partially purified preparation of glucokinase. Anion-exchange chromatography of liver extracts separated glucokinase from a fructose-6-phosphate-sensitive and fructose-1 phosphate-sensitive inhibitor of that enzyme. This inhibitor could be further purified by chromatography on phospho-Ultrogel. It was destroyed by trypsin and was heat-labile. It inhibited glucokinase competitively with respect to glucose and its inhibitory effect was greatly reinforced by fructose 6-phosphate although not by glucose 6-phosphate. Fructose 1-phosphate relieved the enzyme of the inhibitory effect of the regulator and antagonised the effect of fructose 6 phosphate in a competitive manner. It is concluded that the regulator plays a role in the physiological control of the activity of glucokinase, particularly with respect to the stimulatory effect of fructose in isolated hepatocytes (see preceding paper in this journal). PMID- 2917561 TI - Purification, characterization and subcellular localization of pig liver alpha-L iduronidase. AB - alpha-L-Iduronidase was purified about 100,000-fold from pig liver by employing column chromatography on cellulose phosphate (P11), concanavalin A-Sepharose 4B, heparin-Sepharose 4B, Toyopearl HW-55, Sephadex G-100 and chelating Sepharose 6B charged with cupric ions. The molecular mass of the purified enzyme was estimated to be 70 kDa by Sephadex G-100 column chromatography. The purified enzyme gave a single band on disc polyacrylamide gel electrophoresis without using sodium dodecyl sulfate. However, two separate components of 70 kDa and 62 kDa appeared when it was analyzed by SDS/polyacrylamide gel electrophoresis. These 70-kDa and 62-kDa components were confirmed as alpha-L-iduronidase immunochemically. The isoelectric points of these enzymes were both 9.1 as measured by isoelectric focusing in a polyacrylamide gel containing ampholine and sucrose. The optimal pH and Km values were 3.0-3.5 and 65 microM 4-methylumbelliferyl-alpha-L-iduronide, respectively. The purified enzyme was stable in the pH range 3.5-6.0 under conditions with or without 0.5 M NaCl. However, in the presence of 0.5 M NaCl, it was unstable at pH 3.0. Moreover, it was conversely stabilized at pH 7.0 in the presence of 0.5 M NaCl. Immunohistochemically, the enzyme was found in the Kupffer cells and was abundant on their lysosomal membranes. In liver cells, however, the immunohistochemical reaction was weak. PMID- 2917559 TI - Stimulation of glucose phosphorylation by fructose in isolated rat hepatocytes. AB - The phosphorylation of glucose was measured by the formation of [3H]H2O from [2 3H]glucose in suspensions of freshly isolated rat hepatocytes. Fructose (0.2 mM) stimulated 2-4-fold the rate of phosphorylation of 5 mM glucose although not of 40 mM glucose, thus increasing the apparent affinity of the glucose phosphorylating system. A half-maximal stimulatory effect was observed at about 50 microM fructose. Stimulation was maximal 5 min after addition of the ketose and was stable for at least 40 min, during which period 60% of the fructose was consumed. The effect of fructose was reversible upon removal of the ketose. Sorbitol and tagatose were as potent as fructose in stimulating the phosphorylation of 5 mM glucose. D-Glyceraldehyde also had a stimulatory effect but at tenfold higher concentrations. In contrast, dihydroxyacetone had no significant effect and glycerol inhibited the detritiation of glucose. Oleate did not affect the phosphorylation of glucose, even in the presence of fructose, although it stimulated the formation of ketone bodies severalfold, indicating that it was converted to its acyl-CoA derivative. These results allow the conclusion that fructose stimulates glucokinase in the intact hepatocyte. They also suggest that this effect is mediated through the formation of fructose 1 phosphate, which presumably interacts with a competitive inhibitor of glucokinase other than long-chain acyl-CoAs. PMID- 2917562 TI - Alanine dehydrogenase from Streptomyces fradiae. Purification and properties. AB - Alanine dehydrogenase was purified to homogeneity from a cell-free extract of Streptomyces fradiae, which produces tylosin. The enzyme was purified 1180-fold to give a 21% yield, using a combination of hydrophobic chromatography and ion exchange fast protein liquid chromatography. The relative molecular mass of the native enzyme was determined to be 210,000 or 205,000 by equilibrium ultracentrifugation or gel filtration, respectively. The enzyme is composed of four subunits, each of Mr 51,000. Using analytical isoelectric focusing the isoelectric point of alanine dehydrogenase was found to be 6.1. The Km were 10.0 mM for L-alanine and 0.18 mM for NAD+. Km values for reductive amination were 0.23 mM for pyruvate, 11.6 mM for NH4+ and 0.05 mM for NADH. Oxidative deamination of L-alanine proceeds through a sequential-ordered binary-ternary mechanism in which NAD+ binds first to the enzyme, followed by alanine, and products are released in the order ammonia, pyruvate and NADH. PMID- 2917563 TI - Specific S-thiolation of a 30-kDa cytosolic protein from rat liver under oxidative stress. AB - Thin-gel isoelectric focusing (IEF) is a simple and sensitive method of quantifying S-thiolation of individual proteins (protein mixed-disulfide formation). IEF of rat liver cytosol identified one major protein (pI 7.0) which underwent S-thiolation with glutathione disulfide to produce two acidic bands with pIs 6.4 and 6.1. The S-thiolated forms of the protein were purified by preparative isoelectric focusing. An apparent molecular mass of 30 kDa was determined by SDS/polyacrylamide gel electrophoresis. The 30-kDa protein amounted to 7 +/- 2% of the total cytosolic protein on IEF. The most abundant soluble protein of freshly isolated hepatocytes, with an identical isoelectric point to the liver 30-kDa protein, was modified in a similar manner in response to oxidative stress induced by model compounds. Addition of 50 microM tert-butyl hydroperoxide, 50 microM diamide [1,1-azobis(N,N'-dimethylformamide)] or 20 microM menadione (2-methyl-1,4-naphthoquinone) initiated the S-thiolation within less than 2 min in the hepatocytes. These compounds, at the concentrations employed, did not result in cell death. Menadione produced slowly progressive S thiolation of the protein, while tert-butyl hydroperoxide or diamide produced rapid S-thiolation that decreased quickly after 2 min. PMID- 2917564 TI - The multiplicity of troponin T isoforms. Distribution in normal rabbit muscles and effects of chronic stimulation. AB - Polyclonal antibodies were raised in guinea pigs against troponin-T (TnT) isoforms purified from fast- and slow-twitch rabbit muscles. With the use of these antibodies and immunoblots of one- and two-dimensional electrophoreses, the distribution of fast and slow TnT isoforms was investigated in normal and chronically stimulated hindlimb muscles of the rabbit. According to differences in their apparent molecular masses, six fast TnT isoforms (TnTcf, TnT1f, TnT2f, TnT3f, TnT4f, TnT5f) were distinguished in normal tibialis anterior and extensor digitorum longus muscles. These muscles also contained low amounts of TnT1s and TnT2s which were the predominant TnT isoforms in slow-twitch soleus muscle. Fast and slow TnT isoforms were found to exist in several charge variants, i.e. one for TnTcf, three different charge forms for TnT1f, seven for TnT2f, four for TnT3f, three for TnT4f, one for TnT5f, four for TnT1s, and three for TnT2s. Some charge variants were phosphorylated isoforms because treatment with alkaline phosphatase reduced the number of the 19 fast and 7 slow variants to 12 and 3, respectively. The stimulation-induced fast-to-slow transition caused progressive decreases in fast and increases in slow isoforms. The decrease and the disappearance of the major fast isoforms followed a sequence of TnT2f, TnTcf, TnT4f, TnT1f, and TnT3f. This decrease in fast isoforms fits well with the reduction of fast TnT mRNAs assessed by Northern blot analysis. Prolonged stimulation ultimately created a TnT isoform pattern similar to that found in normal slow-twitch muscle. Stimulation also induced changes in the tropomyosin subunit pattern with a decrease in the fast and an increase in the slow alpha tropomyosin subunit without altering the alpha/beta-tropomyosin subunit ratio. Similar to slow-twitch soleus muscle, long-term stimulated muscles contained appreciable amounts of the fast alpha-tropomyosin subunit, but only traces of fast TnT isoforms. This combination indicated that the predominant slow TnT isoforms may be capable of interacting with fast tropomyosin in these muscles. PMID- 2917565 TI - Structural features of lipoprotein lipase. Lipase family relationships, binding interactions, non-equivalence of lipase cofactors, vitellogenin similarities and functional subdivision of lipoprotein lipase. AB - A structural homology between lipoprotein lipase, pancreatic lipase and hepatic lipase is known and indicates that all three lipases are members of a common protein family. Lipoprotein lipase and pancreatic lipase utilize small protein co factors, apolipoprotein C-II and co-lipase, respectively, but comparisons reveal no homology between the co-factor molecules. Hence, they do not show the same relationship as their target enzymes. Neither do screenings detect any extensive similarities between lipoprotein lipase, serine hydrolases, or apolipoproteins. Scannings against data bank proteins show that a 105-residue segment of lipoprotein lipases exhibits a 35-40% residue identity with a sub-region of Drosophila vitellogenins. One fifth of the conserved amino acid residues (8 of 40) are glycine, a pattern which is typical of distantly related forms of protein families. This supports a true relationship between large segments of Drosophila vitellogenins and lipases. Physiological and functional aspects of the vitellogenin/lipoprotein lipase similarities are given. The region concerned is entirely within the N-terminal domain of lipoprotein lipase and constitutes the segment where the similarity to hepatic and pancreatic lipases is most pronounced. Within this lipase region a 10-residue putative lipid-binding site exists for which further similarities have been found to the otherwise not closely related lingual/gastric lipases, prokaryotic lipases and lecithin cholesterol acyltransferase. Another segment in lipoprotein lipase, where the heparin-binding site has been mapped, exhibits a correlation between strength of heparin binding and extent of basic residues among members of the lipase family. It further exhibits weak similarities with the 'Zn-finger' DNA-binding segment of steroid hormone receptors and may indicate convergence in a binding interaction. Thus, a functional subdivision of lipoprotein lipase into different segments can be distinguished. PMID- 2917566 TI - Sequence analysis of the lpdV gene for lipoamide dehydrogenase of branched-chain oxoacid dehydrogenase of Pseudomonas putida. AB - The production of two lipoamide dehydrogenases by Pseudomonas is so far unique. One, LPD-val, is the specific E3 component of the branched-chain-oxoacid dehydrogenase and the second, LPD-glc, is the E3 component of 2-oxoglutarate dehydrogenase and the L-factor of the glycine oxidation system. The objective of the present research was to determine the nucleotide sequence of the structural gene for LPD-val in order to compare its deduced amino acid structure with that of other redox-active disulfide flavoproteins. Northern blots using mRNA isolated from P. putida grown in media with branched-chain amino acids identified a transcript of 6.2 kb which is long enough to encode all the structural genes for the complex. The nucleotide sequence of the structural gene for LPD-val, lpdV, was determined and consists of 459 codons plus the stop codon. The open reading frame begins two bases after the stop codon for the E2 subunit and is composed of 66.3% G + C. Codon usage is characteristic of moderately strongly expressed genes. There is a ribosome-binding site preceding the ATG start codon and a strong candidate for a rho-independent terminator at the 3' end of the reading frame. The Mr of the protein encoded is 48,164 and when the Mr of FAD is added, the total Mr is 48,949, which is very close to the value of 49,000 obtained by SDS-polyacrylamide gel electrophoresis. Similarity comparisons of LPD-val with sequences of three other lipoamide dehydrogenases showed that LPD-val was somewhat more distantly related. It is probable that the lipoamide dehydrogenases and the glutathione and mercuric reductases evolved from a common ancestral flavoprotein. PMID- 2917567 TI - The quaternary structure of the dihydrolipoyl transacetylase component of the pyruvate dehydrogenase complex from Azotobacter vinelandii. A reconsideration. AB - After limited proteolysis of the dihydrolipoyl transacetylase component (E2) of Azotobacter vinelandii pyruvate dehydrogenase complex (PDC), a C-terminal domain was obtained which retained the transacetylase active site and the quaternary structure of E2 but had lost the lipoyl-containing N-terminal part of the chain and the binding sites for the peripheral components, pyruvate dehydrogenase and lipoamide dehydrogenase. The C-terminus of this domain was determined by treatment with carboxypeptidase Y and shown to be identical with the C-terminus of E2. Together with the previously determined N-terminus and the known amino acid sequence of E2, a molecular mass of 27.5 kDa was calculated. From the molecular mass of the native catalytic domain, 530 kDa, and the symmetry of the cubic structures observed on electron micrographs, a 24-meric structure is concluded instead of the 32-meric structure proposed previously. From the effect of guanidine hydrochloride on the light-scattering of intact E2 it was concluded that dissociation occurs in a two-step reaction resulting in particles with an average mass 1/6 that of the original mass before the N----D transition takes place. Cross-linking experiments with the catalytic domain indicated that the multimeric E2 is built from tetramers and that the tetramers are arranged as a dimer of dimers. A model for the quaternary structure of E2 is given, in which it is assumed that the tetrameric E2 core of PDC is formed from each of the six morphological subunits located at the lateral face of the cube. Binding of peripheral components to a site that interferes with the cubic assembly causes dissociation, resulting in the unique small PDC of A. vinelandii. PMID- 2917568 TI - Synthesis and characterization of 1-substituted 5-alkylphenazine derivatives carrying functional groups. AB - The following 1-substituted derivatives of 5-methylphenazine and 5-ethylphenazine were synthesized: 1-(3-carboxypropyloxy)-5-methylphenazine (1B), 1-(3 carboxypropyloxy)-5-ethylphenazine (2B), 1-(3-ethoxycarbonylpropyloxy)-5 ethylphenazine (2C) and 1-[N-(2-aminoethyl)carbamoylpropyloxy]-5-ethylphenazine (2D); their spectra, stability and reactivity as electron mediators were investigated, together with those of 5-methylphenazine (1A) and 5-ethylphenazine (2A). The 1-substituted derivatives are all insensitive to light and the derivatives of 5-ethylphenazine are more stable than those of 5-methylphenazine under neutral and alkaline conditions; 2B is the most stable of all the derivatives. The spectral properties of the decomposed compounds showed that photodecomposition of 1A and 2A is associated with hydroxylation at position 1, alkali decomposition of 1A and 1B with elimination of the 5-methyl group and alkali decomposition of 2A, 2B, and 2D with a ring-opening reaction. The second order rate constant k1 for the reaction of the phenazine derivatives with NADH was measured under steady-state conditions. The k1 values vary depending on the substituents at positions 1 and 5: the values for 1A, 1B, 2A, 2B, 2C and 2D are 1.83 mM-1 s-1, 3.33 mM-1 s-1, 0.75 mM-1 s-1, 1.42 mM-1 s-1, 1.68 mM-1 s-1 and 2.03 mM-1 s-1, respectively. The rate constants, k2 and k3, for the reactions of the reduced form of 2B with oxygen and with 3-(4',5'-dimethylthiazole-2-yl)-2,5 diphenyltetrazolium ion, respectively, were k2 = 1.21 mM-1 s-1 and k3 = 91 mM-1 s 1. These phenazine derivatives have potential applications in the biochemical field. PMID- 2917569 TI - Preparation and kinetic properties of 5-ethylphenazine-poly(ethylene glycol)-NAD+ conjugate, a unique catalyst having an intramolecular reaction step. AB - 5-Ethylphenazine-poly(ethylene glycol)-NAD+ conjugate (EP+-PEG-NAD+) was prepared by linking 1-(3-carboxypropyloxy)-5-ethylphenazine (I) to poly(ethylene glycol) bound NAD+ (PEG-NAD+) and its kinetic properties were studied. As a reference compound, poly(ethylene glycol)-bound 5-ethylphenazine derivative (III) was also prepared and the effects of poly(ethylene glycol) on the reaction rate of the 5 ethylphenazine moiety with NADH was investigated. The second-order rate constant, k1, of the reaction of III with NADH is 2.78 mM-1 s-1 and is about 1.7 times that of 1-(3-ethoxycarbonylpropyloxy)-5-ethylphenazine (II) with NADH. A similar effect of the attached poly(ethylene glycol) was observed for the reaction of PEG NADH with I or II. The second-order rate constants, k2 and k3, of the reactions of the reduced form of III with oxygen and with 3-(4',5'-dimethylthiazole-2-yl) 2,5-diphenyltetrazolium ion, respectively, were k2 = 1.22 mM-1 s-1 and k3 = 32 mM 1 s-1; the k2 value is not changed but the k3 value is decreased by the attachment of the polymer. EP+-PEG-NAD+ works as a unique catalyst having an intramolecular reaction step within its turnover cycle in a coupled multi-step reaction system containing malate dehydrogenase, malate, EP+-PEG-NAD+, a tetrazolium salt and oxygen. The first-order rate constant, k4, of the intramolecular reaction was 1.1 s-1. The effects of the covalent linking of the 5 ethylphenazine and the NAD+ moieties were estimated by comparing the value of k4 with that of k1 for the reaction of III with NADH; the effective concentration of the NADH moiety for the 5-ethylphenazine moiety on the same EP+-PEG-NADH molecule (or vice versa) was calculated to be 0.40 mM from the ratio of k4/k1. The values of the rate constants in the coupled multi-step reaction system enable us to understand the dynamic features of the system and the characteristics of EP+-PEG NAD+ as a catalyst are discussed. PMID- 2917570 TI - Molecular characterization of a Dictyostelium discoideum gene encoding a multifunctional enzyme of the pyrimidine pathway. AB - We have isolated and characterized a Dictyostelium discoideum gene (PYR1-3) encoding a multifunctional protein that carries the three first enzymatic activities of the de novo pyrimidine biosynthetic pathway. The PYR1-3 gene is adjacent to another gene of the pyrimidine biosynthetic pathway (PYR4); the two genes are separated by a 1.5-kb non-coding sequence and transcribed divergently. The PYR1-3 gene is transcribed to form a 7.5-kb polyadenylated mRNA. As with the other genes of the pyrimidine biosynthetic pathway, the PYR1-3 mRNA level is high during growth and decreases sharply during development. We have determined the nucleotide sequence of 63% of the coding region of the PYR1-3 gene. We have identified the activities of the protein encoded by the D. discoideum PYR1-3 gene by comparison of amino acid sequences with the products of genes of known function. The PYR1-3 gene contains four distinct regions that probably correspond to four domains in the protein. From the NH2 extremity to the COOH extremity, these domains are: glutamine amidotransferase, carbamoylphosphate synthetase, dihydroorotase and aspartate transcarbamylase. This organization is identical to the one found in the rudimentary gene of Drosophila. The evolutionary implications of this finding are discussed. PMID- 2917571 TI - Refolding human serum albumin at relatively high protein concentration. AB - The conditions for refolding reduced and denatured human serum albumin (HSA) were investigated with a view to maximising the yield of native monomeric albumin. Refolding by dialysis was found to be preferable to dilution as a means of chaotrope (urea) and reductant (2-mercaptoethanol) removal. Dialysis of denatured HSA solutions containing 4-8 M urea and 14 mM 2-mercaptoethanol at pH 10.0 was found to be optimal for HSA refolding. The yield of monomeric HSA was maximal (94%) for dialysis in the presence of EDTA (1 mM) and sodium palmitate (20 microM). Using this protocol it was possible to refold HSA at concentrations in excess of 5 mg.ml-1 whilst maintaining a high recovery of native monomer. These results represent a considerable improvement on established methods of HSA refolding. PMID- 2917572 TI - Purification, characterization and revised amino acid sequence of a second thioredoxin from Corynebacterium nephridii. AB - A second thioredoxin, distinct from the one reported by Meng and Hogenkamp in 1981 (J. Biol. Chem. 256, 9174-9182), has been purified to homogeneity from an Escherichia coli strain containing a plasmid encoding a Corynebacterium nephridii thioredoxin. Thioredoxin genes from C. nephridii were cloned into the plasmid pUC13 and transformants were identified by complementation of a thioredoxin negative (trxA-) E. coli strain. The abilities of the transformants to support the growth of several phages suggested that more than one thioredoxin had been expressed [Lim et al. (1987) J. Biol. Chem. 262, 12114-12119]. In this paper we present the purification and characterization of one of these thioredoxins. The new thioredoxin from C. nephridii, designated thioredoxin C-2, is a heat-stable protein containing three cysteine residues/molecule. It serves as a substrate for C. nephridii thioredoxin reductase and E. coli and Lactobacillus leichmannii ribonucleotide reductases. Thioredoxin C-2 catalyzes the reduction of insulin disulfides by dithiothreitol or by NADPH and thioredoxin reductase and is a hydrogen donor for the methionine sulfoxide reductase of E. coli. Spinach malate dehydrogenase (NADP+) and phosphoribulokinase are activated by this thioredoxin while glyceraldehyde-3-phosphate dehydrogenase (NADP+) is not. Like the thioredoxin first isolated from C. nephridii, this new thioredoxin is not a reducing substrate for the C. nephridii ribonucleotide reductase. The complete primary sequence of this second thioredoxin has been determined. The amino acid sequence shows a high degree of similarity with other thioredoxins. Surprisingly, in contrast to the other sequences, this new thioredoxin contains the tetrapeptide -Cys-Ala-Pro-Cys- at the active site. With the exception of the T4 thioredoxin, this is the first example of a thioredoxin that does not have the sequence -Cys-Gly-Pro-Cys-. Our results suggest that, like plant cells, bacterial cells may utilize more than one thioredoxin. PMID- 2917573 TI - Synthesis and biological activity of N6-(N[(4-azido-3,5,6-trifluoro)-pyridin-2 yl]-2-aminoethyl)-adenosine 5'-monophosphate, a new AMP photoactivatable derivative. Covalent modification of horse liver alcohol dehydrogenase. AB - N6-(N-[(4-Azido-3,5,6-trifluoro)pyridin-2-yl]-2-aminoethyl)- adenosine 5' monophosphate has been synthesized and evidence presented for its structural assignment by ultraviolet and 19F-NMR spectroscopies. Its photolysis was shown to occur within 5 min. This AMP derivative behaves as a competitive inhibitor of NAD+ in horse-liver-alcohol-dehydrogenase-promoted oxidation of ethanol, with a Ki (0.95 mM) comparable to the Ki of AMP (1.9 mM). Moreover it is an activator of the enzyme when nicotinamide ribose is used as the oxidation cofactor. This activation is as good as that promoted by AMP or by the well known 8-azido-AMP. Upon photolysis of this new derivative in the presence of horse liver alcohol dehydrogenase, a covalent enzyme--analogue complex was isolated and assayed as a catalyst in the oxidation of ethanol using nicotinamide ribose as the cofactor. The reaction took place without complementation of AMP, indicating clearly that the AMP analogue is mainly covalently bound in the AMP-binding site, and that the linkage formed between the enzyme and the azido derivative has not dramatically altered the active site of the enzyme. A similar experiment with 8-azido-AMP produced a completely inactive complex. PMID- 2917574 TI - Carbohydrate structure of glycoprotein 65 encoded by the polycythemia-inducing strain of Friend spleen focus-forming virus. AB - The secondary envelope-gene product, glycoprotein 65 (gp65), of the polycythemia inducing variant of Friend spleen focus-forming virus (F-SFFVp) was isolated from F-SFFVp-infected normal rat kidney cells cultivated in the presence or absence ( Glc) of glucose. Oligosaccharide side chains present were sequentially liberated by treatment of tryptic glycopeptides with endo-beta-N-acetylglucosaminidase H and peptide N-glycosidase F and fractionated by high-performance liquid chromatography. The glycans were characterized by digestion with exoglycosidases, by chromatographic comparison with oligosaccharide standards and by methylation analysis. The results demonstrate that gp65 contains oligomannosidic, hybrid and N-acetyllactosaminic glycans. The oligomannosidic glycans represent the same partially glucosylated species with six to nine mannose residues present in F SFFVp gp52, the biosynthetic precursor of gp65 [Strube, K.-H. Schott, H.-H. and Geyer, R. (1988) J. Biol. Chem. 263, 3762-3771]. Oligosaccharides of the hybrid type were found to comprise one sialylated lactosamine unit and three or four alpha-linked mannose residues. Analysis of the N-acetyllactosaminic glycans revealed that gp65 carries fucosylated, partially sialylated bi-antennary, tri antennary and tetra-antennary oligosaccharides, in addition to incomplete species. The glycosylation of gp65(-Glc) is characterized by the presence of oligomannosidic glycans with five to nine mannose residues, similar hybrid-type species and by increased amounts of incomplete N-acetyllactosaminic oligosaccharides, a decrease in sialylation and the lack of tetra-antennary species. PMID- 2917575 TI - Evaluation of the metal-ion-coordinating differences between the 2'-, 3'- and 5' monophosphates of adenosine. AB - The stability constants of the 1:1 complexes formed between Mg2+, Ca2+, Sr2+, Ba2+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+ or Cd2+ and 2'AMP2-, 3'AMP2- or 5'AMP2- were determined by potentiometric pH titration in aqueous solution (I = 0.1 M, NaNO3; 25 degrees C). The experimental conditions were carefully selected such that self association of the nucleotides and their complexes is negligibly small; i.e. it was made certain that the properties of the monomeric divalent-metal-ion--AMP [M(AMP)] complexes were studied. Based on recent measurements with simple phosphate monoesters, R-MP2- where R is a non-coordinating residue [Massoud, S. S. & Sigel, H. (1988) Inorg. Chem. 27, 1447-1453], it is shown that all the M(AMP) complexes of the alkaline earth ions, with the possible exception of Mg(5'AMP), have exactly the stability expected for a sole-phosphate coordination of the metal ion. The same property is revealed for the complexes with Mn2+, Co2+, Zn2+ or Cd2+ and 3'AMP2-; in case of Ni(3'AMP) and Cu(3'AMP) a slight stability increase just at the edge of the experimental-error limits is indicated. This slight stability increase is attributed to the formation of a macrochelate (possibly with N-3); in fact, additional information confirms macrochelation for Cu(3'AMP). About 45% of Cu(2'AMP) exists in aqueous solution as a macrochelate (probably involving N-3); the other M(2'AMP) complexes (M2+ = Mn2+, Co2+, Ni2+, Zn2+, Cd2+) form (if at all) only traces of a base-backbound species. Most pronounced is macrochelate formation with 5'AMP2-: all mentioned 3d ions and Zn2+ or Cd2+ form to some extent macrochelates via N-7 (the structures of these closed species are indicated). In case of M(5'AMP) the base-binding site is certain: replacement of N-7 by a CH unit (tubercidin 5'-monophosphate) eliminates any increased complex stability, whereas formation of the 1,N6-etheno bridge to form 1,N6-ethenoadenosine 5'-monophosphate results in the phenanthroline-like N-6,N-7 site which facilitates macrochelation significantly. PMID- 2917576 TI - Dynamic of the HPV infection in uterine cervix: colposcopic findings and cyto histological relationship. AB - The Author report in the large investigation in Panama people by colposcopy and cytohistological findings concerning the dynamic of the HPV infection in uterine cervix. The results confirm the absolute efficiency of the methodology in the early diagnosis prevention and therapy. PMID- 2917577 TI - Lymph nodal metastases and pathological patterns in cervical cancer: a critical review. AB - We analyzed 8 pathological factors in order to recognize which of them are statistically significant in worsening the stage of cervical cancer. Three factors (external third invasion, CLS, parametrial invasion) are highly significant (p less than 0.001) as regards lymphatic metastases, while no one statistical relation has been found among grading or histotype and cervical canal invasion. Comparing the 8 pathologic factors among themselves, we have observed that parametrium, corpus and CLS are highly related to external third (p less than 0.001); in the same way corpus is related to cervical canal and parametrium to CLS (p less than 0.001). PMID- 2917578 TI - Anterior spread of gynaecological neoplasias: reliability between some diagnostic procedures. AB - The Authors report their experience regarding the comparison between pre-surgical clinico-instrumental staging and intra-operative staging in 134 patients with gynaecological neoplasias, particularly considering the spread to the lower urinary tract. The analysis of the results shows the moderate reliability of the cystoscopy in routinely evaluating extension of gynaecologic malignant diseases. The association of cytological urinary sediment examination with cystoscopy improves the possibility of a better evaluation. On the contrary, vesical biopsy, performed on the indications of cystoscopy and urinary cytology, and standard excretory urography prove to be insensitive indicators in diagnosing the spread of gynaecological malignancies. PMID- 2917579 TI - Morphological changes of the ovarian surface epithelium in women with ovarian polycystic disease or endometrial carcinoma and a control group. AB - The ovarian surface epithelium and that of related inclusion cysts were studied in 50 women with ovarian polycystic disease and they were compared with our preceding observations performed on women with endometrial carcinoma (n = 50) and on women without any hyperplastic or neoplastic genital tract pathology (n = 50). In 16 women (32%) the ovarian epithelium with normal aspect was found on the surface of the ovary and in inclusion cysts. In the remaining 34 women (68%) surface papillomatosis, hyperplastic and metaplastic changes were present on the ovarian surface and/or in the inclusion cysts. These findings were similar to those observed in the group of women with endometrial adenocarcinoma, while the surface epithelium was often normal in the control group. Our observations confirm the hypothesis of a hormonal influence in the hyperplastic and metaplastic modifications of the ovarian epithelium and in the related common epithelial tumors of the ovary. PMID- 2917580 TI - Diagnostic and therapeutic procedures in the vulvar intraepithelial neoplasia (VIN) and early invasive cancer of the vulva. AB - The study comprised 71 women from 1st Clinic of Gynecology Medical Academy of Cracow from 30 to 76 years (means = 52.5) with VIN and early invasive cancer of the vulva. The clinical examination, colposcopy, cytology, histology of target biopsy and culture of microorganisms taken from the vulva were performed in all cases. 36 cases with VIN I, 14 cases with VIN II, 17 cases with VIN III and 4 cases with early invasive carcinoma were found. The local anti-inflammatory procedure was used in all cases with VIN I, 8 cases with VIN II and 4 cases with VIN III. In 6 women with VIN III and in 3 with VIN II lyocal excision of unifocal lesions was performed. In 4 women with VIN III and 4 with the early invasive carcinoma simple vulvectomy was applied. After treatment with local anti inflammatory agents, the total regression of the lesion was observed in 92.9% cases with VIN I, and 75% with VIN II. In 6 women treated with cryocoagulation positive therapeutic effects were noted. In 1 out of 6 cases with VIN III treated by the local excision, the recurrence of the lesion was observed. Among 8 women, after simple vulvectomy, 5 cases have been observed for more than 5 years, and are considered cured. PMID- 2917581 TI - Validity of rapid estimation of erythrocyte volume in the diagnosis of polycytemia vera. AB - In the diagnosis of polycytemia vera, estimation of erythrocyte volume (EV) from plasma volume (PV) and venous hematocrit (Hctv) is usually thought unadvisable, because the ratio of whole body hematocrit to venous hematocrit (f ratio) is higher in patients with splenomegaly than in normal subjects, and varies considerably between individuals. We determined the mean f ratio in 232 consecutive patients suspected of polycytemia vera (f = 0.967; SD 0.048) and used it with each patient's PV and Hctv to calculate an estimated normalised EVn. With measured EV as a reference value, EVn was investigated as a diagnostic test. By means of two cut off levels the EVn values could be divided into EVn elevated, EVn not elevated (both with high predictive values), and an EVn borderline group. The size of the borderline EVn group ranged from 5% to 46% depending on position of the cut off levels, i.e. with the efficiency demanded from the diagnostic test. EV can safely and rapidly be estimated from PV and Hctv, if f is determined from the relevant population, and if the results in an easily defineable borderline range of EVn values are supplemented by direct EV determination. PMID- 2917582 TI - A modified scintigraphic technique for amputation level selection in diabetics. AB - A modified 123I-antipyrine cutaneous washout technique for the selection of amputation levels is described. The modifications imply a reduction of time needed for the examination by simultaneous recordings on different levels, and a better patient acceptance by reducing inconvenience. Furthermore, both skin perfusion pressure (SPP) and skin blood flow (SBF) are determined from each clearance curve. In a prospective study among 26 diabetic patients presenting with ulcers or gangrene of the foot, both SPP and SBF were determined preoperatively on the selected level of surgery and on adjacent amputation sites. These 26 patients underwent 12 minor foot amputations and 17 major lower limb amputations. Two of these amputations failed to heal. SBF values appeared indicative for the degree of peripheral vascular disease, as low SBF values were found with low SPP values. SPP determinations revealed good predictive values: all surgical procedures healed when SPP greater than 20 mmHg, but 2 out of 3 failed when SPP less than 20 mmHg. If SPP values would have been decisive, the amputation would have been converted to a lower level in 6 out of 17 cases. This modified scintigraphic technique provides accurate objective information for amputation level selection. PMID- 2917583 TI - Radioimmunoscintigraphy of ovarian cancer with 131-iodine labeled OC-125 antibody fragments. AB - Radioimmunoscintigraphy (RIS) with 131I labeled OC-125 F(ab')2 monoclonal antibody fragments was prospectively studied in 43 women for primary diagnosis and follow up of ovarian cancer. Total body planar photoscans with a scintillation camera were performed one to seven days after antibody application and results were compared with operation and or CT examination. By the region of interest technique the tumor to non tumor tissue ratio (T/N) was calculated in vivo. Sensitivity in primary diagnosis was 100% (10/10), specificity 33% (1/3). For local recurrency, sensitivity was 86% (19/22), for metastatic loci 80% (17/21). Specificity was 75% and 50%. T/N ratio was in the rage from 1.3 to 2.8. Sensitivity for ovarian cancer is high in primary diagnosis and follow up. By the region of interest technique it is possible to detect small recurrencies and to presume peritoneal carcinosis. Antibody accumulations in diseases different from ovarian cancer however diminish specificity. PMID- 2917584 TI - Increased theophylline clearance in asthmatic patients due to terbutaline. AB - The pharmacokinetic mechanism of the theophylline-terbutaline interaction has been studied. Sustained release theophylline 200-400 mg b.d. was given with placebo or terbutaline 2.5 mg t.d.s. to six adult asthmatic patients. Terbutaline decreased the serum trough theophylline levels from 8.1 to 7.3 micrograms/ml, improved daily the clinical score from 1.51 to 1.26 and increased the peak expiratory flow rate from 316 to 370 l/min. In a single dose study following the chronic therapy, it was shown that there was no change in the peak theophylline concentration or in the timing of the peak, but the t1/2 was reduced from 9.0 to 7.5 h, and the systemic clearance was increased from 20.2 to 24.8 ml.h-1.kg-1. Thus, terbutaline reduced the serum theophylline concentration by increasing its systemic clearance. PMID- 2917585 TI - The relationship between theophylline clearance and age in adult life. AB - Fifty three subjects (31 normal volunteers and 22 patients with asthma) between the ages of 20 and 87 years had their theophylline clearance measured. Volume of distribution (V) and terminal elimination half-life (t1/2) were also calculated in the volunteers who received i.v. theophylline. Although patients tended to have higher clearance values than volunteers, in both groups the oldest third had the lowest clearances. For the combined group (corrected for the patient effect) the oldest third (mean age 70 years) had a mean clearance of 0.53 versus 0.72 for the middle third (mean age 47 years) and 0.73 ml/min/kg CBW for the youngest third (mean age 26 years). There was no statistically significant age related change in V/kg CBW but t1/2 did rise with increasing age. Thus, although clearance does not fall with increasing age during younger adult life, there is a fall during late adult life becoming apparent in the seventh, eighth and ninth decades. PMID- 2917587 TI - The effects of alcohol on psychological functions in normal volunteers after 8 days' treatment with pipequaline (PK 8165), diazepam or placebo. AB - The effects of daily administration for 8 days of 50 mg pipequaline, 10 mg diazepam and placebo were assessed in a double-blind cross-over study with 12 healthy volunteers. This study also tested for an interaction between the drugs and alcohol on the eighth day. Subjective ratings, psychomotor and memory performance were evaluated. Diazepam produced the typical pattern of changes, namely impairments in psychomotor performance and reductions in the retention of newly memorised information. In contrast, the effects of pipequaline were relatively minor. In general, neither drug potentiated the effects of alcohol on performance, only isolated instances of non-additive interactions occurring. Subjective reports revealed that whereas both active drugs increased feelings of calmness, this result was accomplished by pipequaline with considerably less drowsiness, no euphoria and a general absence of the adverse side effects of diazepam. PMID- 2917586 TI - Urinary excretion of 6 beta-hydroxycortisol and the time course measurement of enzyme induction in man. AB - The effect of enzyme induction by antipyrine, phenobarbitone and rifampicin on the time-course of urinary 6 beta-hydroxycortisol (6 beta-OHC) excretion was investigated in healthy volunteers. The drugs were given chronically for either seven or 14 days. Significant increases in 6 beta-OHC excretion were observed after 4 days administration of antipyrine (1.2 g), 13 days administration of phenobarbitone (100 mg), and only 2 days administration of rifampicin (0.6 or 1.2 g). During 14 days rifampicin administration (1.2 g) 6 beta-OHC excretion, for individual subjects, reached a maximum on Days 11-14 when excretion was significantly greater than on day 7. On stopping rifampicin, in a 7-day study, excretion decreased over the next six days, but still remained significantly elevated compared to the original control values. These studies show that measurement of urinary 6 beta-hydroxycortisol provides a simple non-invasive method with which to monitor the time-course of enzyme induction by drugs in man. However, the method cannot be used to predict clinically important drug interactions until the cytochrome P-450 enzyme responsible for cortisol 6 beta hydroxylation has been fully characterized. PMID- 2917588 TI - Exercise haemodynamic effects of beta-blockade and intrinsic sympathomimetic activity. AB - Beta-adrenergic blockade with intrinsic sympathomimetic activity (ISA) causes less depression of resting and submaximal heart rate (HR) than non-ISA beta blockers. The effects of these drugs on exercise haemodynamics have not been well studied. We evaluated effects of pindolol, propranolol and placebo during rest and steady-state exercise on cardiac output, oxygen consumption, calf blood flow, HR and blood pressure in 18 healthy subjects. Pindolol 5 mg and propranolol 80 mg given twice daily, reduced maximal exercise HR by 50 and 52 beats.min-1 respectively, confirming similarity of beta 1-blockade. Resting cardiac output was unchanged in all three groups after one week of therapy. Cardiac output, measured during steady-state exercise decreased in the propranolol group (18.3 vs 15.6 l.min-1) with no significant changes in pindolol (15.7 vs 16.01.min-1) or placebo (18.6 vs 17.3 l.min-1). The rise in cardiac output, from rest to exercise, was similarly attenuated by propranolol but not by pindolol or placebo. Exercise stroke volume increased 12% on pindolol (123-140 cc) and decreased 7% on propranolol (143-133 cc). Neither drug had a detrimental effect on exercise calf blood flow compared to placebo. Thus, unlike propranolol, pindolol with ISA, maintains a normal cardiac output during submaximal exercise. PMID- 2917589 TI - 5-Methoxypsoralen increases the sensitivity of the retina to light in humans. AB - The acute effect of 5-methoxypsoralen (5-MOP) on the sensitivity of the retina to visible light in humans has been studied in 11 healthy volunteers 2 h after administration of 5-MOP or placebo given at 09.00 h. Retinal sensitivity was evaluated by electroretinography at 11.00 h. 5-MOP significantly increased the sensitivity of the retina to light under photopic conditions and in the early stages of the dark adaptation period, as observed under scotopic conditions. The findings suggest that melatonin is involved in these changes. PMID- 2917590 TI - Intensive monitoring of adverse drug reactions in infants and preschool children. AB - Intensive monitoring of adverse drug reactions (ADR) in infants and preschool children in the paediatric outpatient unit covering the town of Karlovac (150,000 inhabitants) was performed over a period of three months. Data were obtained by physical examination of children and the history given by their parents. In all 2359 children were examined. ADR were recorded in 63 children and were reported to the National ADR monitoring centre in Zagreb. Using the algorithm of Hutchinson et al. (1979), all ADR were classified as "definite", "probable", "possible" and "unlikely". Drugs were prescribed in 97.3% of children, 60.24% received an antimicrobial agent (43% of them on the basis of a sensitivity test), and an antipyretic was given to 1878 children, mostly paracetamol. ADR were most frequently caused by antibiotics (49 reactions to penicillin V, and 15 to amoxycillin) and secretolytics (7 reactions). ADR were followed by complete recovery and not a single child was hospitalized because of an ADR. The results, when compared with the very small number of broadly comparable studies, indicate that the incidence of ADR in this population is rather small and of minor importance. PMID- 2917591 TI - Effect of diltiazem on the pharmacokinetics of propranolol, metoprolol and atenolol. AB - The pharmacokinetic interaction between diltiazem and three beta-adrenoceptor blockers propranolol, metoprolol and atenolol was investigated in healthy volunteers given diltiazem 30 mg or placebo t.d.s. for 3 days, followed by a single dose of propranolol 20 mg, metoprolol 40 mg or atenolol 50 mg. The AUCs of propranolol and metoprolol were significantly increased after diltiazem and it significantly prolonged the elimination half-life of metoprolol. In contrast, it did not significantly affect the pharmacokinetics of atenolol. Propranolol significantly decreased the resting pulse rate after diltiazem pretreatment as compared to placebo. The results indicate that diltiazem impaired the clearance of propranolol and metoprolol, which are principally metabolized by an oxidative pathway, and that the kinetic interaction between diltiazem and propranolol may partly be related to the significant reduction in the pulse rate produced by the latter. PMID- 2917592 TI - Steady-state intravenous pharmacokinetics of pirenzepine in patients with hepatic insufficiency and combined renal- and hepatic insufficiency. AB - The steady-state intravenous pharmacokinetics of pirenzepine has been investigated in patients with chronic liver disease and others with combined chronic liver disease and renal insufficiency. The plasma clearance (CL) of Pirenzepine, steady-state plasma concentration Cmin(ss) and dominant half life t1/2 gamma were not significantly altered in the chronic liver disease group. In patients with renal and hepatic insufficiency, CL was reduced, t1/2 gamma was prolonged from 11.1 to 19.4 h and Cmin(ss) was elevated from 36 ng/ml to 66 ng/ml compared to healthy controls. Plasma concentrations remained in the therapeutic range and the dosage regimen was well tolerated. Adjustment of the dose of pirenzepine need be considered only in cases of severe impairment of both renal and hepatic elimination. PMID- 2917593 TI - Steady-state intravenous pharmacokinetics of pirenzepine in patients with differing degrees of renal dysfunction. AB - The steady-state intravenous pharmacokinetics of pirenzepine has been investigated in 57 subjects whose renal function ranged from normal to chronic failure requiring regular haemodialysis. Pirenzepine renal clearance, total clearance and terminal (dominant) half-life were found to be correlated with the creatinine clearance (CLCR), but this was not the case for the volume of distribution and the nonrenal clearance. The therapeutic regimen was well tolerated by all subjects. Haemodialysis did not significantly contribute to the elimination of pirenzepine. Dosage adjustment need only be considered in patients with CLCR less than 25 ml/min in order to reduce the frequency of minor side effects. PMID- 2917594 TI - Pharmacokinetics of cefonicid in children. AB - The pharmacokinetics of cefonicid was studied in 17 children requiring antibiotic treatment for respiratory or urinary tract infections. After informed consent had been obtained from the parents, a single dose of cefonicid 50 mg/kg/body weight was given by intramuscular injection. The mean peak serum concentration of 212.63 micrograms/ml was reached at 1.00 h, as absorption occurred at a very fast rate with a mean constant of 3.24 h-1. Mean values for half-life, apparent volume of distribution (Vz), total body clearance (CL), and renal clearance (CLR) were 3.24 h, 0.21 l.kg-1, 16.67 ml.min-1 and 13.60 ml.min-1 respectively. There was an inverse relationship between age and Vz, whereas CL and CLR were positively correlated with age. Cefonicid concentrations in urine were many times higher than the MICs of susceptible strains of bacteria. The study demonstrated that i.m. cefonicid 50 mg.kg-1 gave serum concentrations well within the therapeutic range for susceptible bacteria, and that its pharmacokinetic properties allow single daily doses to be used to treat infections in children. PMID- 2917595 TI - Effect of carteolol on renal function in healthy subjects and patients with hypertension. AB - The effect of short- and long-term administration of carteolol on renal function has been examined in healthy subjects and in hypertensive patients with or without renal failure. In healthy subjects neither a single dose of 10 mg carteolol nor continuous administration of 20 mg/day for 7 days had any effect on creatinine clearance and renal blood flow. In all subjects the clearance rate of carteolol was about 400 ml/min and its fractional excretion of carteolol exceeded 300%, suggesting that the drug is secreted actively from renal tubules. Twenty three hypertensive patients with or without renal dysfunction were given carteolol 10 to 20 mg/day for more than 50 weeks in addition to their standard antihypertensive regimens, which were left changed. Laboratory results were compared with the mean values of 50 weeks before and after the addition of carteolol, and none, including plasma creatinine, blood urea nitrogen and electrolytes, were significantly changed. Neither the estimated glomerular filtration rate nor the effect of the drug on blood pressure changed significantly during this prolonged treatment. It is concluded that carteolol had no effect on renal function in healthy subjects and in hypertensive patients with or without renal failure. PMID- 2917596 TI - 5-Methoxypsoralen increases evening sleepiness in humans: possible involvement of the melatonin secretion. AB - The acute and short-term effect of 5-methoxypsoralen (5-MOP) on daytime sleepiness was investigated in 12 healthy subjects according to a double-blind cross-over design. 5-MOP (40 mg/day) or placebo was orally administered (one week each) at 16.00 h. 5-MOP significantly increases daytime sleepiness 4 to 5 h after administration without affecting the subsequent sleep efficiency and duration. We found a positive correlation between sleepiness and melatonin levels. Our findings suggest that the melatonin secretion may play a role in the effect of 5 MOP on sleepiness in humans. PMID- 2917597 TI - Kinetic and dynamic interactions of oral viqualine and ethanol in man. AB - We have studied the interaction of viqualine, a 5-hydroxytryptamine (5-HT) uptake inhibitor, with ethanol in 16 healthy men aged 20 to 34 years. The subjects were randomly assigned to receive ethanol dosed to maintain blood alcohol concentrations of 17-22 mmol.l-1 (n = 8) or orange juice (n = 8) on each of two test days one week apart and preceded, in random order, by 3 days of viqualine 75 mg bd or placebo. Ethanol had no effect on steady-state viqualine concentrations or the inhibition of 5-HT uptake. Viqualine did not affect acetaldehyde concentrations or cause an aversive alcohol-sensitizing reaction. The deleterious effects of ethanol on word recall, manual tracking, body sway, and self-ratings of intoxication, sedation, and performance were not modified by the presence of viqualine. Within each beverage group performances and self-ratings on viqualine and placebo days were not different. The first dose of viqualine was associated with transient nausea. Viqualine and ethanol do not interact kinetically or dynamically on the variables examined in this study. PMID- 2917598 TI - Effect of cell substratum on lateral mobility of lipids in the plasma membrane of vascular endothelial cells. AB - Bovine vascular endothelial cells can be maintained in a highly differentiated state in vitro, either by the addition of fibroblast growth factor (FGF) to the culture medium or by plating the cells on extracellular matrix (ECM)-coated dishes. Under these conditions the cells proliferate actively and at confluence form a tightly packed monolayer composed of nonoverlapping polarized cells. A fluorescence recovery after photobleaching method was used to determine the lateral mobility coefficient D of the lipophilic fluorescent probe, 5N (hexadecanoyl)-aminofluorescein (HEDAF), in the basal and apical plasma membranes of endothelial cells under various culture conditions (cells on glass coverslips in the presence or absence of FGF, or cells plated on ECM in the exponential growth phase or at confluence). A heterogeneous distribution of lateral diffusion coefficients D was found in a given cell population. Nevertheless, for the basal membrane, a "mean" D value close to 2.0 x 10(-9) cm2/s was found for all the culture conditions. The "mean" D value of HEDAF in the apical pole was slightly higher when sparse cells were exposed to FGF (D = 2.2 x 10(-9) cm2/s) and was further enhanced when cells were growing or confluent on ECM-coated coverslips (D = 2.7 x 10(-9) cm2/s). On the other hand, when the cells were maintained in the absence of FGF on glass coverslips, similar "mean" D values were found in both cell poles (D = 2.0 x 10(-9) cm2/s). These results show that lateral mobility of lipids in endothelial plasmalemma varies in response to external factors such as FGF and the ECM. PMID- 2917599 TI - Double in situ hybridization in combination with digital image analysis: a new approach to study interphase chromosome topography. AB - Double in situ hybridization with mercurated and biotinylated chromosome specific DNA probes in combination with digital image analysis provides a new approach to compare the distribution of homologous and nonhomologous chromosome targets within individual interphase nuclei. Here we have used two DNA probes representing tandemly repeated sequences specific for the constitutive heterochromatin of the human chromosomes 1 and 15, respectively, and studied the relative arrangements of these chromosome targets in interphase nuclei of human lymphocytes, amniotic fluid cells, and fibroblasts, cultivated in vitro. We have developed a 2D-image analysis approach which allows the rapid evaluation of large numbers of interphase nuclei. Models to test for a random versus nonrandom distribution of chromosome segments are discussed taking into account the three dimensional origin of the evaluated 2D-distribution. In all three human diploid cell types the measurements of target-target and target-center distances in the 2D-nuclear image revealed that the labeled segments of the two chromosomes 15 were distributed both significantly closer to each other and closer to the center of the nuclear image than the labeled chromosome 1 segments. This result can be explained by the association of nucleolus organizer regions on the short arm of chromosome 15 with nucleoli located more centrally in these nuclei and does not provide evidence for a homologous association per se. In contrast, evaluation of the interphase positioning of the two chromosome 1 segments fits the random expectation in amniotic fluid and fibroblast cells, while in experiments using lymphocytes a slight excess of larger distances between these homologous targets was occasionally observed. 2D-distances between the labeled chromosome 1 and 15 segments showed a large variability in their relative positioning. In conclusion our data do not support the idea of a strict and permanent association of these homologous and nonhomologous targets in the cell types studied so far. PMID- 2917600 TI - Difference in the expression level of DNA polymerase beta among mouse tissues: high expression in the pachytene spermatocyte. AB - The expression level of DNA polymerase beta was determined in various mouse tissues. Northern blot hybridization analysis using rat cDNA as a probe revealed that the mRNA of about 1.5 kb for this enzyme is present in all kinds of tissues examined, but its content widely varies among tissues; the most abundant DNA polymerase beta mRNA was present in the testis, which was followed by brain, thymus, and spleen. The mRNA content was low in heart, kidney, and liver. In testis and brain, two minor species of transcripts of 3.3 and 6.2 kb were detected in addition to that of 1.5 kb. DNA polymerase beta activities in these tissues were closely correlated with the mRNA content, indicating that the expression of this enzyme is mainly regulated by the level of the mRNA. A survey of DNA polymerase beta mRNA levels in the testes at successive postnatal developmental stages and in isolated spermatogenic cells indicated that DNA polymerase beta mRNA was most abundant in spermatocytes at early pachytene. Since meiotic recombination occurs in this period, DNA polymerase beta may be involved in the repair-type DNA synthesis associated with the recombination process. PMID- 2917601 TI - Alphoid satellite DNA is tightly associated with centromere antigens in human chromosomes throughout the cell cycle. AB - In this study, we have examined a DNA element specific to the centromere domain of human chromosomes. Purified HeLa chromosomes were digested with the restriction enzyme Sau3AI and fractionated by sedimentation through a sucrose gradient. Fractions showing antigenecity to anticentromere (kinetochore) serum obtained from a scleroderma CREST patient were used to construct a DNA library. From this library we found one clone which has specifically hybridized to the centromere domain of metaphase chromosomes using a biotinylated probe DNA and FITC-conjugated avidin. The clone contained a stretch of alphoid DNA dimer. To determine precisely the relative location of the alphoid DNA stretch and the centromere antigen, a method was developed to carry out in situ hybridization of DNA and indirect immunofluorescent staining of antigen on the same cell preparation. Using this method, we have found perfect overlapping of the alphoid DNA sites with the centromere antigen sites in both metaphase chromosomes and nuclei at various stages in the cell cycle. We have also observed this exact correlation at the attachment sites of artificially extended sister chromatids. These results suggest the possibility that alphoid DNA repeats are a key component of kinetochore structure. PMID- 2917602 TI - The effect of aging and dietary restriction on DNA repair. AB - DNA repair was studied as a function of age in cells isolated from both the liver and the kidney of male Fischer F344 rats. DNA repair was measured by quantifying unscheduled DNA synthesis induced by UV irradiation. Unscheduled DNA synthesis decreased approximately 50% between the ages of 5 and 30 months in both hepatocytes and kidney cells. The age-related decline in unscheduled DNA synthesis in cells isolated from the liver and kidney was compared in rats fed ad libitum and rats fed a calorie-restricted diet; calorie restriction has been shown to increase the survival of rodents. The level of unscheduled DNA synthesis was significantly higher in hepatocytes and kidney cells isolated from the rats fed the restricted diet. Thus, calorie restriction appears to retard the age related decline in DNA repair. PMID- 2917603 TI - Correlation of development stage and gap junction formation between chick embryo neurons and cloned skeletal muscle myoblasts. AB - The frequency of gap junction formation between neurons and myoblasts of chick embryo leg skeletal muscle changes as a function of the developmental stage of the muscle. Cells from leg muscle of various ages and states of innervation were first cloned in vitro and then co-cultured with ciliary ganglion, spinal cord, or dorsal root ganglion neurons. The presence of gap junctions between cells was identified by the passage of fluorescent dyes or electric currents from one cell to another. The clones examined were fusing muscle clones (myoblasts) as well as nonfusing clones. Mononuclear cells of either kind of clone derived from legs younger than stage 24 (E4) dye-couple with other clone cells but do not dye couple with neurons. Myoblasts of fusing muscle clones derived from stage 24 through stage 29 (E5) legs dye-couple with neurons at high frequency; nonfusing clones from these same embryos do not contain cells that dye-couple with neurons. Mononuclear cells of both fusing and nonfusing clones from normally innervated stage 30 (E6) through 38 (E12) legs do not dye-couple with neurons at significant frequencies. Additionally, aneural legs of denervated E10-E12 embryos yield muscle clones in which the myoblasts again dye-couple with neurons at high frequency. The ability to form communicating junctions between muscle cells and neurons in culture is restricted to myoblasts cloned from legs of those stages of development and conditions of innervation that define and limit neuron-dependent alteration of myoblast populations in vivo. PMID- 2917604 TI - Phorbol ester-induced activation of protein kinase C leads to increased formation of diacylglycerol in human neutrophils. AB - Human neutrophils stimulated with a phorbol ester (phorbol 12-myristrate 13 acetate or phorbol 12,13-dibutyrate) responded with an increase in diacylglycerol, considered the natural activator of protein kinase C. The amounts of diacylglycerol formed were considerable, reaching 700-900% of basal after 20 min. In contrast, 4-alpha-phorbol 12-myristate 13-acetate did not induce any detectable formation of diacylglycerol. Simultaneously, phorbol 12-myristate 13 acetate exposure caused increased breakdown of both phosphatidylcholine and phosphatidylinositol 4,5-bisphosphate. These results suggest that once activated, protein kinase C can positively modulate its own activity by inducing additional formation of diacylglycerol from at least two different sources. PMID- 2917605 TI - Morphologic and phenotypic changes of human neuroblastoma cells in culture induced by cytosine arabinoside. AB - The effects of cytosine-arabinoside (ARA-C) on the growth and phenotypic expression of a new human neuroblastoma (NB) cell line (GI-ME-N) have been extensively tested. Low doses of ARA-C allowing more than 90% cell viability induce morphological differentiation and growth inhibition. Differentiated cells were larger and flattened with elongated dendritic processes; such cells appeared within 48 h after a dose of ARA-C as low as 0.1 micrograms/ml (about 1000-fold lower than the conventional clinic dose). The new morphological aspect reached the maximum expression after 5-6 days of culture being independent from the addition of extra drug to the culture. A decrease in [3H]thymidine incorporation was also observed within 24 h and the cell growth was completely inhibited on the sixth day. Moreover, ARA-C strongly inhibited anchorage-independent growth in soft agar assay. Membrane immunofluorescence showed several dramatic changes in NB-specific antigen expression after 5 days of treatment with ARA-C. At the same time ARA-C also modulated cytoskeletal proteins and slightly increased catecholamine expression. These findings suggest that noncytotoxic doses of ARA-C do promote the differentiation of GI-ME-N neuroblastoma cells associated with reduced expression of the malignant phenotype. PMID- 2917606 TI - Three-dimensional organization of micronuclei induced by colchicine in PtK1 cells. AB - In PtK1 cells micronucleated by colchicine, we previously demonstrated that some micronuclei contain a single chromosome. Here, we investigated interphase chromosome organization in micronucleated PtK1 cells using conventional electron microscopy and three-dimensional computer reconstruction. The distribution of micronuclei was not always polarized, but in some cells they formed a ring. When this occurred, centrioles and Golgi apparatus were located inside the ring. On freeze-fracture replicas, we observed that nuclear pore distribution among the micronuclei was heterogeneous, and on thin sections some micronuclei displayed an incomplete nuclear envelope, with gaps in the double membrane and areas without lamina or condensed chromatin. By autoradiography, we showed that the fibrillar dots were not sites of active transcription. We applied three-dimensional reconstruction to one micronucleated cell containing 22 micronuclei whose size indicated that each micronucleus probably contained one chromosome. In this cell we demonstrated that only the smallest micronuclei had an incomplete nuclear envelope. The presence in micronuclei of either nucleoli or fibrillar dots was found to be mutually exclusive. These dots might constitute stores of nucleolar proteins which migrate into micronuclei possessing no ribosomal genes. In NOR bearing micronuclei, the structural organization was similar to that of diploid nuclei: the nucleoli were attached to the nuclear membrane and a nucleolar canal was seen, even in single-chromosome spherical micronuclei. Taken together, these findings indicate that in the diploid nuclei of PtK1 cells, the three-dimensional organization of the nucleolar domain seems to be directly controlled by the X chromosome. PMID- 2917607 TI - Regulation of thymidylate synthase gene expression in mouse fibroblasts synchronized by mitotic selection. AB - Previous studies have shown that thymidylate synthase gene expression is regulated over a wide range in response to growth stimulation in cultured mouse fibroblasts. In the present study we show that the gene is also regulated during the cell cycle in continuously growing cells. Our analyses were conducted with a fluorodeoxyuridine-resistant mouse 3T6 cell line that overproduces thymidylate synthase and its mRNA by a factor of 50 due to gene amplification. Cells were synchronized by mitotic selection. RNA blot analyses showed that the amount of thymidylate synthase mRNA increased 5- to 10-fold as cells progressed from G1 through the middle of S phase. S1 nuclease protection assays showed that the pattern of 5' termini of thymidylate synthase mRNA was the same in G1 and S phase. Despite the large increase in thymidylate synthase mRNA content, the level of the enzyme increased only by a factor of 2 as cells progressed from G1 to mid S phase. This apparent discrepancy can be explained by the fact that the enzyme is highly stable. PMID- 2917608 TI - Protein kinase C mediates the hormonally regulated plasma membrane fusion of avian embryonic skeletal muscle. AB - Recent findings have demonstrated that prostanoid-generated calcium fluxes can trigger myoblast fusion and suggest inositol phospholipid turnover as part of the fusion mechanism. Here we demonstrate that a block imposed on myoblast fusion by antagonists of prostanoid biosynthesis can be overcome by either the membrane permeable diacylglycerol, 1-oleoyl-2-acetyl-sn-glycerol (OAG), or 12-O tetradecanoylphorbol 13-acetate (TPA). Both phorbol and the membrane-impermeable dioleoylglycerol were ineffective. These results implicate protein kinase C activation in prostaglandin E1-mediated myoblast fusion and add weight to the contention that inositol turnover is involved in the regulation of myoblast fusion. PMID- 2917609 TI - Dominance and independent segregation of metabolic cooperation-competence and pluripotency in an embryonal carcinoma cell hybrid. AB - We report the isolation of a fusion hybrid, PR3, from a pluripotent embryonal carcinoma (EC) cell line, PSA4, which is metabolic cooperation-competent, and an EC line R5/3OA which has a reduced capacity for metabolic cooperation and a restricted developmental capacity. PR3 resembles its pluripotent parent PSA4 in its capacity for gap-junction-mediated transfer of uridine nucleotides and in its pluripotency both in embryoid bodies in vitro and in tumors in vivo. This enabled the relationship between pluripotency and metabolic cooperation to be examined by the selection of segregant lines. Cooperation-deficient lines were isolated from a thioguanine-resistant intermediate line (PR3Tg12) using "Kiss of Death" selection. A novel method was devised for the selection of differentiation deficient segregants using feeder cell-conditioned medium which partially inhibits in vitro differentiation. It was found that communication-competence and in vitro pluripotency segregated independently, demonstrating that the loss of developmental capacity in R5/3OA cannot be attributed to its communication deficiency. PMID- 2917610 TI - Cell-surface location and molecular properties of cell-CAM 105 in intestinal epithelial cells. AB - Cell-CAM 105 is involved in intercellular adhesion of isolated rat hepatocytes in vitro. In addition to liver, cell-CAM 105 occurs in several different epithelia, in platelets, and in granulocytes. In this paper we present a detailed analysis of cell-CAM 105 in the small intestinal mucosa. Isolated rat intestinal epithelial cells and brush-borders were investigated by indirect immunofluorescence. A strong fluorescence occurred in the brush-border region and a much weaker staining was seen in the lateral cell surfaces. The brush-border staining was heterogeneous and concentrated to the periphery where brush-border microvilli from adjacent cells are in contact with each other. It is suggested that cell-CAM 105 might mediate binding between the outer surfaces of neighboring microvilli. Immunoblotting and electrophoretic analyses of the biochemical properties of intestinal cell-CAM 105 demonstrated significant differences compared with cell-CAM 105 isolated from liver. Intestinal cell-CAM 105 was smaller than liver cell-CAM 105 under reducing conditions, whereas it was larger than liver cell-CAM 105 under non-reducing conditions. Chemical reduction decreased the size of intestinal cell-CAM 105, but increased the size of liver cell-CAM 105. Our interpretation of these data is that intestinal cell-CAM 105 occurs as a part of a macromolecular complex. This interpretation was supported by electrophoretic analyses of intestinal cell-CAM 105 isolated by immunoaffinity chromatography on anti-cell-CAM antibodies. In addition to cell-CAM 105, this material contained several other proteins of lower molecular weight than cell-CAM 105. These data suggest that intestinal cell-CAM 105 participates in cell-surface interactions that may regulate the structure and function of the apical brush border regions of the intestinal epithelial cells. PMID- 2917611 TI - Binding, internalization, and degradation of basic fibroblast growth factor in human microvascular endothelial cells. AB - The binding, internalization, and degradation of basic fibroblast growth factor (bFGF) in human omental microvascular endothelial cells (HOME cells) were investigated. Binding studies of bFGF in human endothelial cells have not yet been reported. Basic FGF bound to HOME cells (KD of 42.0 +/- 3.8 pM and 70,526 +/ 6121 binding sites/cell for the high-affinity sites, KD of 0.933 +/- 0.27 nM and 630,252 +/- 172,459 sites/cell for low-affinity binding sites). The number of low affinity binding sites was found to be variable. Washing the cells with 2 M phosphate-buffered saline removed completely 125I-bFGF bound to low-affinity binding sites but decreased also the high-affinity binding. The majority of the surface-bound 125I-bFGF was removed by washing the cells with acetic acid buffer at pH 3. At 37 degrees C, 30% of the cell-associated 125I-bFGF became resistant to the acidic wash after 90 min, suggesting that this fraction of bound 125I-bFGF was internalized. At this temperature, degradation of the internalized ligand was followed after 1 h by the appearance of three major bands of 15,000, 10,000, and 8,000 Da and was inhibited by chloroquine. These results demonstrated two classes of binding sites for bFGF in HOME cells; the number of high-affinity binding sites being larger than the number reported for bovine capillary endothelial cells. The intracellular processing of bFGF in HOME cells seems to be different from that of heparin binding growth factor-1 in murine lung capillary endothelial cells and of eye-derived growth factor-1 in Chinese hamster fibroblasts. PMID- 2917612 TI - Ultrastructural changes in nucleoli and fibrillar centers under the effect of local ultraviolet microbeam irradiation of interphase culture cells. AB - As shown previously, ultraviolet (uv) microbeam irradiation of one of the two mature nucleoli within an interphase cell nucleus causes significant diminution and inactivation of the irradiated nucleolus and compensatory growth and activation of the nonirradiated one. In the present work we describe the results of an ultrastructural study of this phenomenon. The changes in the nucleoli were examined by means of complete series of ultrathin sections obtained from seven irradiated pig kidney cells. The compensatory hypertrophy of the nonirradiated nucleoli is shown to be accompanied by a nearly twofold increase in the number of fibrillar centers (FCs) and by a decrease in their linear dimensions compared with the control cells of the same ploidy. In the degraded nucleoli the number of FCs decreases, but their dimensions increase. Ultraviolet microbeam irradiation causes dramatic diminution of the dense fibrillar component within the irradiated nucleoli as well. The nucleolar capacity for compensatory hypertrophy indicates that in addition to active ribosomal genes, mature nucleoli also contain "silent" genes capable of being activated under extreme conditions to sustain the required level of rRNA synthesis. It is assumed that activation of latent ribosomal genes is accompanied by FC "fragmentation" without a considerable increase in their total volume per cell. PMID- 2917613 TI - Truckin' pneumonia--an outbreak of Q fever in a truck repair plant probably due to aerosols from clothing contaminated by contact with newborn kittens. AB - We describe an outbreak of Q fever affecting 16 of 32 employees at a truck repair plant. None of the cases were exposed to cattle, sheep or goats, the traditional reservoirs of Q fever. The cases did not work, live on, or visit farms or attend livestock auctions. One of the employees had a cat which gave birth to kittens 2 weeks prior to the first case of Q fever in the plant. The cat owner fed the kittens every day before coming to work as the cat would not let the kittens suckle. Serum from the cat had high antibody titres to phase I and phase II Coxiella burnetii antigens. The attack rate among the employees where the cat owner worked, 13 of 19 (68%), was higher than that of employees elsewhere, 3 of 13 (28%) [P less than 0.01]. The cat owner's wife and son also developed Q fever. None of the family members of the other employees with Q fever was so affected. We conclude that this outbreak of Q fever probably resulted from exposure to the contaminated clothing of the cat owner. PMID- 2917614 TI - Seroepidemiological study of the transmission of the mumps virus in St. Lucia, West Indies. AB - A seroepidemiological study of the prevalence of mumps virus specific antibodies reveals a pattern of endemic persistence on the island of St Lucia in the West Indies. In the unvaccinated population the proportion seropositive rose rapidly in the child age classes to attain a stable plateau close to unity in value in the teenage and adult age groups. The average age at infection was estimated to be between 3 and 4 years of age and the average duration of detectable levels of maternally derived antibodies was approximately 3 months. Analyses based on mathematical models of the transmission dynamics of the virus suggest that in excess of 75% of each cohort of 1- to 2-year-old children must be effectively immunized to eliminate mumps virus transmission. A mumps radial haemolysis test, developed for quantitative measurements of antibody, is discussed. PMID- 2917616 TI - Exposure to Legionellaceae at a hot spring spa: a prospective clinical and serological study. AB - Following the occurrence of five cases of Legionnaires' disease among patients and therapists at a French hot spring spa, a series of cleansing procedures and an epidemiological study were undertaken. During a 3-month period, the spring water was repeatedly sampled. Serum samples were taken from 689 randomly selected patients, 230 therapists, 134 administrative staff and a control group of 904 blood donors. Legionellaceae were present in the spring water at concentrations of 10(3)-10(5) colony forming units/l. Fifteen different species or serogroups were isolated with Legionella pneumophila serogroups 3 and 1 predominating. No clinical cases of Legionnaires disease were observed during the study. However, 11% of the therapists and 5% of the patients either had a high titre of antibody (greater than or equal to 256) to at least one species or serogroup or seroconverted during the study. Mean antibody titres in the three study groups were significantly higher than those in the blood donors against 11 of the 32 legionella antigens tested. Nine of these 11 antigens corresponded to species or serogroups isolated from the spring water. The highest mean antibody titres in all three study groups were against L. pneumophila serogroup 3, the most common legionella in the spring water. These findings have important implications for the maintenance of adequate standards of hygiene, bacteriological sampling and clinical surveillance in this and similar establishments. PMID- 2917615 TI - Legionella pneumophila in a hospital in Torino, Italy. A retrospective one-year study. AB - Legionella pneumophila serogroup 1 was isolated from post mortem specimens from 13 out of 58 patients with pneumonia diagnosed at autopsy. The results of a study undertaken in the hospital environment showed that the water plumbing system was colonized with L. pneumophila serogroup 1 which could also be isolated from respiratory devices filled with tap water. Control measures instituted are described. PMID- 2917617 TI - Campylobacter jejuni isolations from Mexican and Swedish patients, with repeated symptomatic and/or asymptomatic diarrhoea episodes. AB - The presence of different Campylobacter jejuni serotypes in Swedish patients with diarrhoea and in Mexican patients with or without diarrhoea was investigated with special reference to repeated isolations during the course of infection and to symptomatic and asymptomatic episodes. The study included 136 C. jejuni isolates from 62 Mexican children and 173 isolates from 68 Swedish patients. The bacteria were serotyped for heat-stable (HS) and heat-labile (HL) antigen. Swedish patients, all with symptoms, were in general only infected with one serotype and were rarely reinfected. Mexican patients on the other hand were in general infected with mixed serotypes and frequently reinfected without symptoms with new, different serotypes, a finding which is in concordance with a theory of an induced immunity to surface antigens. PMID- 2917618 TI - Campylobacter jejuni and Campylobacter coli diarrhoea in rural and urban populations in Yugoslavia. AB - During a 4-month period during the summer of 1985, campylobacters were isolated from 338 (16.3%) of 2080 patients with acute diarrhoea attending the University Hospital of Infectious Diseases in Zagreb. Of these isolates 220 (64.1%) were Campylobacter jejuni and 118 (34.9%) were C. coli. The patients were drawn from three residential zones in and around Zagreb: inner city, peripheral city and rural. Incidences of campylobacter diarrhoea ranged from 71 per 100,000 per year in inner city residents to 99 per 100,000 per year in the rural residents. Most infections were in young children; the incidence in infants ranged from 800 to 2500 per 100,000 per year in the inner city and rural zones respectively. The isolation rate from faecal specimens of infants from the rural zone was 61%. The ratio of isolation rates in males and females (all ages) was 1.1:1, but in infants it was 0.7:1 and in patients over the age of 65 years it was 0.4:1. The incidence of C. coli in the rural zone was four times that in the inner city and twice that in the peripheral zone. This survey shows that campylobacter infection in Zagreb has distinctive epidemiological features. The transmission of infection appears to be midway between that found in industrialized and developing countries, and there is an unexplained excess of C. coli infection. PMID- 2917620 TI - Mode of action of erythropoietin (Epo) in an Epo-dependent murine cell line. II. Cell cycle dependency of Epo action. AB - Erythropoietin (Epo), a glycoprotein hormone, regulates the proliferation and differentiation of committed erythroid progenitor cells. We investigated the effect of Epo on the kinetics of an Epo-dependent cell line (DA-1ER), which was cloned from the murine interleukin 3-dependent cell line, DA-1. Flow cytometry and [3H]thymidine incorporation were used to analyze the cell cycle. Removal of Epo from the culture medium resulted in the accumulation of the cells in the G1 phase. Eighteen hours after the removal of Epo, 75%-80% of the cells were arrested in G1 phase. Readdition of Epo to these quiescent cells allowed them to progress from the G1 to the S phase with a lag period of 10 h. Epo was required throughout the lag period in order to achieve maximal DNA synthesis. When the cells were arrested in the G2/M phase or the G1/S interphase by colcemid and thymidine, respectively, and then released from the arrest, they could complete the cell cycle in the absence of Epo. These findings suggest that Epo is only required in the G1 phase for the cells to progress through the cell cycle. PMID- 2917619 TI - A norfloxacin dose finding study for selective decontamination of the digestive tract in pigs. AB - Five pigs were treated orally with norfloxacin for 5 consecutive days in two well separated periods. This was done to determine the lowest dose required to free the pigs of Enterobacteriaceae. In the first period of the study, the animals were treated with 400 mg per day while in the second treatment 800 mg norfloxacin was given. Daily faecal culturing indicated that the faeces became free of Enterobacteriaceae in 3-5 days when treated with 400 mg/day, while all animals were found negative on culturing after 3 days of treatment with 800 mg/day. Investigation of the concentration of norfloxacin in the faeces revealed that a substantial fraction of the dose was either absorbed or inactivated by faecal substances. An in vitro study in faeces confirmed that a substantial part, some 75% of the dose, may have been inactivated by intestinal contents. This finding helps to explain the much lower concentration of 120 mg norfloxacin per kg of faeces in the pig in comparison with the almost tenfold higher concentration reported to develop in man during treatment with an identical dose. PMID- 2917621 TI - Ultrastructural localization of platelet factor 4 in rat megakaryocytes and platelets by gold-labeled antibody detection. AB - The pattern of distribution of platelet factor 4 (PF-4) was studied in rat platelets and megakaryocytes following immunohistochemical labeling with a monoclonal antibody (2E7) specific for PF-4 and visualization by a protein A-gold complex. We observed a heterogeneity in PF-4 expression among alpha granules with a minority of them being unlabeled by immunoelectron microscopy, a pattern similar in both mature, circulating platelets and developing megakaryocytes. Furthermore, the majority of the labeled alpha granules in both cell types displayed a unique, eccentric localization of the PF-4 that was mainly over the nucleoid region within each granule. This localization is similar to the microtubular localization in alpha granules reported previously for von Willebrand factor and yet distinct from the reported random distribution of fibrinogen. We also observed significant labeling of small vesicular structures in developing megakaryocytes that may be involved in the transport of PF-4 and its packaging in platelet alpha granules. This new information is important in relating patterns of PF-4 biogenesis in megakaryocytes to conditions of alpha granular dysfunction in platelets. PMID- 2917622 TI - Effects of isobaric hypoxia on murine medullary and splenic megakaryocytopoiesis. AB - Hypoxia stimulates erythropoiesis and inhibits megakaryocytopoiesis in the bone marrow of mice. However, the effects of hypoxia on megakaryocytopoiesis in the spleen are unknown. Mice were exposed to hypoxia by enclosure in cages covered with dimethyl-silicone rubber membranes for 1-14 days. The mice were sacrificed at intervals after exposure to hypoxia and blood, femurs, and the spleen were analyzed. One femur and the spleen were processed for measurement of megakaryocyte diameter and number. Marrow smears were made from the other femur and stained to identify the small acetylcholinesterase-positive (SAChE+) cell, a megakaryocyte precursor. Results showed a linear increase in packed cell volumes, a decrease in platelet counts, and a cycling of splenic volume with time in hypoxia. After 14 days of hypoxia, the relative number of megakaryocytes was decreased greater than 80% in the bone marrow and spleen; SAChE + cells were decreased greater than 65%. Splenic volume and megakaryocyte concentration were altered and the absolute number of splenic megakaryocytes cycled throughout the experiment. Mean megakaryocyte diameter increased after day 10 in the marrow and was inversely related to absolute megakaryocyte number in the spleen. Changes in megakaryocyte diameter and number with hypoxia suggest a compensatory mechanism for increasing platelet production, which may be regulated separately in the bone marrow and spleen. Results of this study support the hypotheses of stem cell competition between erythropoietic and megakaryocytic cell lines, and the autoregulation of megakaryocyte size and number. PMID- 2917623 TI - Low antigen density leukemia cells: selection and comparative resistance to antibody-mediated marrow purging. AB - Low tumor-associated antigen (TAA) expressing tumor cells present an obstacle to effective antibody directed purging of tumor cells from bone marrow. In this study, a comparison was made of the efficiency with which low TAA expressing leukemia cells could be depleted using two monoclonal antibody (MoAb) directed purging techniques: 1) complement (C)-mediated cytolysis, and 2) physical separation using magnetic microspheres. Low TAA sublines were selected from a cultured human leukemia cell line by growing out cells remaining after treatment with anti-TAA and C, or after immunomagnetic (IM) purging. IM-selected sublines showed lower TAA expression than did C-selected sublines, and sublines resulting from multiple selections expressed less TAA than those that had only been through one selection. These sublines were then examined for sensitivity to C or IM purging. The highly selected, lowest TAA expressing sublines were markedly resistant to both IM and C. Less selected sublines were resistant to C, but not to IM. In both techniques, addition of MoAbs against a second TAA restored the efficiency of purging to that observed with the parental line. When low TAA subline cells were seeded into simulated bone marrow and subjected to purging, C mediated lysis removed less than 40% of leukemia cells, whereas IM purging removed 85% of the cells. These results indicate that there are low antigen density cells that are resistant to C-mediated purging, but which retain sensitivity to IM removal. PMID- 2917624 TI - The hematopoietic stem cell compartments in mice during and after long-term inhalation of three doses of benzene. AB - Female BDF1 mice were exposed for 16 weeks to airborne concentrations of 100, 300, and 900 ppm of benzene, 6 h per day, 5 days per week. Bone marrow hemopoietic stem cell compartments and peripheral blood cell counts were studied using clonal assays and standard methods. Dose-dependent depressive effects were observed on all stem cell compartments. Only the erythroid colony-forming units (CFU-E) compartment was depressed during exposures to 100 ppm; CFU-E were more sensitive than the erythroid burst-forming units (BFU-E), spleen CFU (CFU-S), or G-M CFU (CFU-C) during exposure to 300 ppm or 900 ppm. Lymphocytopenia was observed in the peripheral blood. After benzene-free intervals, a regeneration of lymphocyte numbers and slow normalization of stem cell numbers was seen. Complete recovery from the 16 weeks exposure to 300 ppm was seen between 73 and 185 days. PMID- 2917625 TI - Effects of human fetal liver extract on the growth of HL-60 cells. AB - Two kinds of HL-60 cell growth suppressor present in human fetal liver were studied. One is the already known arginase, which showed nonspecific suppression on the growth of HL-60 cells and human granulocyte-macrophage progenitors (CFU GM), and the other, a new species of suppressor with the characteristics of lower molecular weight (less than 10,000 daltons), shows preferential suppression on HL 60 cell growth, but less effect on the growth of CFU-GM. PMID- 2917626 TI - Trichinella spiralis: the fate of the accessory layer of the cuticle of infective larvae. PMID- 2917627 TI - Schistosoma haematobium: analysis of eggshell protein genes and their expression. AB - Eggshell protein genes of Schistosoma mansoni that encode a 14 kDa protein have been shown to be highly conserved and expressed in a sex-, tissue-, and temporal specific manner. To initiate studies on the eggshell protein genes of S. haematobium, a cDNA probe, pSMf 61-46, representing a S. mansoni eggshell protein mRNA was used to screen a S. haematobium genomic library. Of the seven independent recombinant clones isolated, two (lambda SH 2-1 and lambda SH 6-1) were analyzed and compared to those of S. mansoni. lambda SH 2-1 and lambda SH 6 1 each contain a different genomic copy of the gene encoding a 19.8 and 17.6 kDa protein, respectively. This is due to an additional 78 bp present in the coding region of lambda SH 2-1 relative to lambda SH 6-1. The rest of the coding sequences are identical, and the 5' and 3' untranslated regions are nearly identical. The deduced amino acid sequences of S. haematobium eggshell proteins are very rich in glycine (47 and 50%) when compared to 43.5% glycine in the protein encoded by S. mansoni. Long stretches of glycines, as many as 15 in a row, occur in the S. haematobium sequence. DNA comparison of the eggshell protein genes of the two schistosome species yielded an overall homology of 83.1%. The homology is much higher in the 5' and 3' untranslated regions than in the protein coding regions. Genomic clones of both species contained second open reading frames, which appeared to be kept open as a consequence of the amino acid composition of the other. There are no introns in S. haematobium or S. mansoni eggshell protein genes, and the genomic Southern data indicated a similar arrangement of these genes in the genome of both species. Primer extension experiments and dideoxynucleotide sequencing of the RNA determined the mRNA cap site sequence as ATCAT and ATCAC in lambda SH 2-1 and lambda SH 6-1, respectively. Northern blot analysis determined the size of the mRNA to be about 1.0 kp. Expression of the RNA from these genes appears to be regulated in a manner similar to the corresponding genes in S. mansoni. mRNA is found only in mature females and first appears at 70 days after infection of hamsters. DNA sequence comparisons of the 5' flanking regions of S. haematobium and S. mansoni eggshell protein genes to each other and to those of silkmoth and Drosophila revealed several short sequence elements that are shared.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2917628 TI - pH-dependent uptake and macrofilaricidal effects of chloroquine on adult filarial parasites in vitro. AB - Uptake and macrofilaricidal effects of chloroquine (CQ) and other aminoquinolines were found to be highly pH dependent in Brugia pahangi, Acanthocheilonema viteae, Onchocerca volvulus, and Dirofilaria immitis. Using [3H]CQ, it was found that all of the parasites took up more drug under alkaline conditions (RPMI 1640 at pH 8.4) than in neutral (pH 7.4) or acidic (pH 6.8) media. Differences were seen in the amount of drug taken up among the filariae studied. B. pahangi and A. viteae took up 7 times more chloroquine per milligram of tissue than did O. volvulus, and 30 times more than D. immitis during a 60-min incubation period at pH 8.4. Sensitivity to the aminoquinolines also increased with increasing media pH, and was measured using parasite motility as an indicator of drug efficacy. Potency of chloroquine against B. pahangi increased 100-fold at pH 8.4 compared to pH 7.4. A. viteae and O. volvulus showed similar sensitivity to chloroquine compared to B. pahangi; D. immitis was less sensitive. While uptake of chloroquine was linear from pH 6.8 to 8.4, B. pahangi was unaffected by 32 microM of the drug below pH 7.6; at any pH above this, motility of this parasite was completely inhibited. Calculations of the internal pH of this parasite indicated that it shifted upwards significantly with changes in media pH. It was concluded that these shifts in internal pH may render parasites more sensitive to the effects of chloroquine. PMID- 2917629 TI - Antigenic proteins of Eimeria maxima gametocytes: cell-free translation and detection with recovered chicken serum. AB - RNA was extracted from isolated Eimeria maxima gametocytes and translated in a rabbit reticulocyte cell-free protein synthesis system. The major cell-free translation products from E. maxima gametocyte RNA ranged from 225 to 50 kDa, distinct and different from uninfected chicken intestine cell-free translation products. Rabbit antiserum to E. maxima gametocytes as well as recovered chicken sera specifically precipitated some of the major gametocyte cell-free products. A time course of infected intestine RNA indicated that these cell-free synthesized gametocyte antigens appear at 130 to 138 hr postinfection. PMID- 2917630 TI - Nematospiroides dubius: influence of adjuvants on immunity in mice vaccinated with antigens isolated by affinity chromatography from adult worms. AB - Five adjuvants were examined for their ability to potentiate the immune response of mice to soluble antigens from adult Nematospiroides dubius prepared by affinity chromatography against antibodies from repeatedly infected mice as ligands (IMIgAg). Immunized mice were better protected against N. dubius by IMIgAg injected intraperitoneally with either pertussigen (75%) or aluminium hydroxide (Alum) (67%) as adjuvants than with Freud's complete (54%) or incomplete adjuvants (31%). Protection was correlated with elevated specific antibody values and with cellular responses. Quil A was toxic to recipient mice at the concentration used. Alum may be a more practical adjuvant than pertussigen, which may activate protective immunity only in specific recipient genotypes and oil-based adjuvants which appear to be less efficient, to vaccinate mice with soluble parasite antigens. PMID- 2917631 TI - Trypanosoma brucei: frequent loss of a telomeric variant surface glycoprotein gene. AB - We have observed the loss of an inactive telomeric variant surface glycoprotein (VSG) gene that is located on a minichromosome in Trypanosoma brucei. If this is due to gene conversion, it is the third "silent" gene conversion (i.e., one that does not produce an antigenic switch) detected in 19 antigenic switches of the IsTaR 1 serodeme. This is surprisingly frequent since the immune response cannot select against the inactive gene. We estimate that 10(-1) to 10(-3) telomeric VSG gene conversions occur per generation, which is at least 100 times more frequent than antigenic switching. Since all three "silent" gene conversions involved an IsTat 5 VSG gene, the frequency may vary among telomeric VSG genes. However, the high gene conversion frequency for the 5 VSG gene does not ensure a higher antigenic switch frequency than other telomeric VSG genes for which we have probes. These results suggest that gene conversion rapidly alters the repertoire of telomeric VSG genes, possibly including those on minichromosomes, producing a continual variation in the VSG genes that are more likely to be expressed. PMID- 2917632 TI - Trichostrongylus colubriformis: epithelial cell kinetics in the small intestine of infected rabbits. AB - Epithelial cell kinetic parameters were compared in intestines of control and Trichostrongylus colubriformis infected rabbits using a microdissection and metaphase accumulation technique in regions of gut with heavy (proximal site) and small (distal site) burdens of worms. In control animals, the cell production rates were respectively 4.3 cells/crypt/hr in the proximal region and 3.7 cells/crypt/hr in the distal one; and the influx of cells onto villi were respectively 67.5 cells/hr and 37.4 cells/hr. In the parasitized rabbits, in the main site of infection, a fourfold increase was recorded in the cell proliferation rate and in the influx of cells onto villi. In the region distal to the main site of infection, the same parameters were twice the control values, although only a low number of T. colubriformis were recovered from this part of gut. These large modifications in the epithelial renewal probably underlies the morphological and enzymological changes previously described in both parts of the T. colubriformis infected gut. PMID- 2917633 TI - Is the histological classification of chronic granulocytic leukaemia justified from the clinical point of view? AB - By means of morphometric techniques, in 100 untreated Ph'-positive chronic granulocytic leukaemia (CGL) patients the main features from the initial bone marrow biopsy were analyzed, with particular attention being paid to morphological and quantitative study of megakaryocytes. The number of megakaryocytes per mm2 of marrow tissue showed a mean value of 25.3 (SD +/- 18.8), and was positively correlated with either platelet counts, blood percentage of basophils and blast cells, or spleen and liver size. Based on the number and morphological characteristics of megakaryocytes, patients were classified as having granulocytic CGL (67 cases) or the so-called chronic megakaryocytic-granulocytic myelosis (33 cases), but except for higher platelet counts and blood percentages of basophils and blast cells in the latter, no relevant clinical, evolutionary or prognostic differences were observed between the groups. Such results cast doubt on the validity of histological classification of CGL from the clinical point of view. PMID- 2917634 TI - Follicular low-grade non-Hodgkin's lymphoma: long-term outcome with or without tumor progression. AB - Long-term outcome for 127 patients with follicular low-grade lymphoma was investigated. Therapy included radiotherapy (n = 23), low toxicity chemotherapy with or without radiotherapy (n = 76), or more intensive chemotherapy (n = 22). 6 patients had no initial therapy. Complete remission was obtained in 67% of patients. For patients under 60 years of age median survival was 8.7 yr compared with 3.8 yr for older patients, but survival from lymphoma was identical for the two age-groups: 75% at 5 yr, and 58% at 10 yr. The relatively low tumor mortality contrasted with a relapse-free survival of 30% at 10 yr, and relapse 8-9 yr after first remission. Examining the disease topography and the stability of histologic subtype in 78 patients with recurrent lymphoma, two types of relapse with different prognoses were identified: 1) with tumor progression (lymphoma dissemination to atypical extranodal sites and/or histologic conversion to an intermediate/high-grade lymphoma) seen in 56% of patients with a survival from lymphoma of 13% at 10 yr; and 2) without tumor progression (involvement of nodal sites, and unchanged histology) seen in 44% with a survival from lymphoma of 77% at 10 yr. Actuarial risk of tumor progression was 44% at 5 yr, and 67% at 10 yr. Except from the negative impact of a large tumor burden, it was not possible to identify patients with high risk for tumor progression. More important than all pretreatment factors was poor response to initial therapy (p = 0.0001). Due to lack of reliable risk factors, it is recommended that all younger patients be treated with the intention of achieving complete remission; a significant fraction might be curable. PMID- 2917635 TI - Treatment of acute myeloid leukemia in elderly patients with oral idarubicin as a single agent. AB - Idarubicin (IDR) is a new anthracycline that can be administered orally. Oral IDR was given at a dose of 30 mg/m2 daily for 3 d in 20 patients aged 65 to 79 yr with previously untreated acute myeloid leukemia (AML). 5 patients whose marrow remained blastic at d 14 received a second course. 8 patients achieved complete remission (6 after one single course). There were: 1 early death, 4 deaths in aplasia, 7 failures. The hematologic toxicity was high. All but 1 patient had to stay in hospital and the duration of neutropenia was 12 to 34 d (median 19). Oral IDR is an effective therapy for AML in elderly patients but the total dose of 90 mg/m2 is too aggressive to be administered safely outside the hospital. PMID- 2917636 TI - Chronic myelogenous leukemia and Klinefelter's syndrome. AB - A case of chronic myelogenous leukemia with Klinefelter's syndrome mosaicism in a 27-yr-old male is reported. Cytogenetic analysis provided evidence that the Philadelphia chromosome occurred monoclonally in the XXY cells but not in the XY cells. PMID- 2917637 TI - Avascular necrosis of the femoral head in acute leukemia patients treated with combination therapy including steroids. PMID- 2917638 TI - Androgens in hairy cell leukaemia: an overlooked treatment? PMID- 2917639 TI - Three successful pregnancies in a woman with essential thrombocythemia. PMID- 2917640 TI - 'Pink test' and osmotic fragility test for the diagnosis of hereditary spherocytosis: another view. PMID- 2917641 TI - Genetic transfer of the pigment bacteriorhodopsin into the eukaryote Schizosaccharomyces pombe. AB - The gene encoding for bacterio-opsin (bop gene) from Halobacterium halobium has been introduced in a yeast expression vector. After transformation in Schizosaccharomyces pombe, bacterio-opsin (BO) is expressed and was detected by antisera. The precursor protein of BO (pre-BO) is processed by cleavage of amino acids at the N-terminal end as in H. halobium. Addition of the chromophore, retinal, to the culture medium results in a slight purple colour of the yeast cells indicating the in vivo regeneration of BO to bacteriorhodopsin (BR) and its incorporation into membranes. Therefore, in contrast to the expression in E. coli, isolation of the membrane protein and reconstitution in lipid vesicles is not necessary for functional analysis. The kinetics of the ground state signal of the photocycle BR in protoplasts is demonstrated by flash spectroscopy and is comparable to that of the natural system. The present investigation shows for the first time the transfer of an energy converting protein from archaebacteria to eukaryotes by genetic techniques. This is a basis for further studies on membrane biogenesis, genetics, and bioenergetics by analysis of in vivo active mutants. PMID- 2917642 TI - Stabilisation of cathepsin E by ATP. AB - The hydrolysis of 3 distinct substrates by cathepsin E from human red blood cells and gastric mucosa was measured in the presence and absence of physiologically relevant concentrations of ATP. At pH values below about 5.0, the nucleotide was without effect. However, at pH 5.8, whereas cathepsin E was virtually inactive by itself, it was restored to full activity (kcat) by ATP and the non-hydrolysable methylene-ATP analogue. At still higher pH values, kcat progressively diminished but significant levels of cathepsin E activity were readily detectable at pH 7.0. The specificity of this stabilisation effect was examined. PMID- 2917643 TI - Polarographic observation of substrate-level phosphorylation and its stimulation by acetylcholine. AB - Substrate-level phosphorylation was observed under the conditions optimal for this process and opposite to those for oxidative phosphorylation. Polarographic registration of Ca2+ stimulated alpha-ketoglutarate oxidation and self-inhibition of uncoupled alpha-ketoglutarate (KG) oxidation was used. Acetylcholine (ACh) administration stimulated KG oxidation and substrate-level phosphorylation in isolated mitochondria. These effects are stronger in tissues with a higher level of endogenous acetylcholine, such as guinea pig liver vs rat liver and pancreas vs liver. The specific stimulation of KG oxidation by ACh is related to a decrease of succinate oxidation and is contrary to the specific stimulating effect of adrenaline on succinate oxidation. Therefore the existence of reciprocal hormone-substrate-nucleotide systems is suggested. The described set of conditions optimal for substrate-level phosphorylation observation by polarographic registration of respiration is as convenient as the ADP test for the investigation of oxidative phosphorylation. PMID- 2917644 TI - Ba2+-sensitive K+ channels in luminal-membrane vesicles from pars convoluta of rabbit proximal tubule. AB - This paper describes properties of 86Rb+ fluxes through a novel K+ channel in luminal-membrane vesicles isolated from pars convoluta of rabbit proximal tubule. The uptake of 86Rb+ into potassium salt loaded vesicles was specifically inhibited by Ba2+. The isotope accumulation is driven by an electrical diffusion potential as shown in experiments using these membrane vesicles loaded with anions of different membrane permeability and was as follows: gluconate greater than SO4(2-) greater than Cl-. Furthermore, the vesicles containing the channels show a cation selectivity with the order K+ greater than Rb+ greater than Li+ greater than Na+ = choline+. PMID- 2917645 TI - Possible involvement of protein kinase C in proliferation and differentiation of osteoblast-like cells. AB - In cloned osteoblast-like cells, MC3T3-E1, 12-O-tetradecanoylphorbol-13-acetate (TPA), a protein kinase C activating phorbol ester, and 1-oleoyl-2-acetylglycerol (OAG), a specific activator for protein kinase C, stimulated DNA synthesis in a dose-dependent manner. Both TPA and OAG acted synergistically with insulin-like growth factor I to stimulate DNA synthesis. TPA as well as OAG suppressed the increase in alkaline phosphatase activity of MC3T3-E1 cells induced by parathyroid hormone. These results suggest that protein kinase C is involved in the process which directs osteoblast-like cells toward proliferation. PMID- 2917647 TI - Complete amino acid sequence of the sarcoplasmic calcium-binding protein (SCP-I) from crayfish (Astacus leptodactylus). AB - The complete amino acid sequence of the alpha chain of the dimeric sarcoplasmic Ca2+-binding protein (SCP-I = alpha 2) from crayfish (Astacus leptodactylus) has been determined by partial automatic sequencing of the peptides derived from tryptic digests of the protein after citraconylation or treatment with 1,2 cyclohexanedione. Overlapping peptides were obtained by cleavage with o iodosobenzoic acid, or digestion with Staphylococcus aureus protease, thermolysin and pepsin. The acetylated N-terminus was identified by fast atom bombardment mass spectrometry. The monomeric protein contains 192 amino acids and has an Mr of 21,643. The sequence shows the presence of three calcium-binding sites and perhaps of two others that may be degenerated. PMID- 2917646 TI - Molecular architecture of secretin receptors: the specific covalent labelling of a 51 kDa peptide after cross-linking of [125I]iodosecretin to intact rat pancreatic acini. AB - p-Azidophenylglyoxal (APG), a heterobifunctional reagent with one group reacting selectively with arginine residues and another group photoactivable, was used to cross-link [125I]secretin prebound to intact rat pancreatic acini. The best yield was obtained when the [125I]secretin-acini complex was incubated under dim light with 2 mM APG at 37 degrees C and pH 8.0, followed by photolysis at 312 nm. The main secretin binding peptide cross-linked under reducing conditions, when tested by SDS-PAGE and autoradiography: (i) had a molecular mass of 51 kDa and was not a subunit of a larger disulfide-linked structure, and (ii) was distinct from the main VIP binding peptide coexisting in the same preparation. PMID- 2917648 TI - Mechanism of inhibition of papain by chicken egg white cystatin. Inhibition constants of N-terminally truncated forms and cyanogen bromide fragments of the inhibitor. AB - N-terminally truncated forms of chicken egg white cystatin and its cyanogen bromide fragments were isolated and assayed for inhibition of papain. Truncated forms beginning with Gly-9 and Ala-10 had a 5000-fold lower affinity for papain than the two isoelectric forms (pI = 6.5 and 5.6) of the full-length inhibitor (Ki = 6 pM and 7 pM) or a truncated form beginning with Leu-7 (Ki = 6 pM), indicating the outstanding importance of one or two residues preceding conserved Gly-9 for binding. A weak inhibition of papain (Ki = 900 nM) was exhibited by the intermediate cyanogen bromide fragment (residues 30-89) containing the chicken cystatin QLVSG variation of the QVVAG segment which is conserved in almost all members of the cystatin superfamily. The obtained affinity data provide independent evidence for the validity of the proposed docking model of a chicken cystatin-papain complex [(1988) EMBO J. 7, 2593-2599]. PMID- 2917649 TI - Influence of thyroid status on the membranes of rat liver mitochondria. Unique localization of L-glycerol-3-phosphate dehydrogenase. AB - The effect of thyroid status on the physical properties of rat liver mitochondrial membranes and on the lipid microenvironment of proteins was investigated. The steady-state fluorescence anisotropy of diphenyl-1,3,5-triene and 1-[4-(trimethylaminophenyl)phenyl]-6-phenylhexa-1,3,5-triene revealed an increase of the order of the membranes with the increase of hormone level. Protein arrangement in the inner mitochondrial membrane altered with the thyroid status, which was reflected by digitonin subfractionation of mitochondria. The microenvironment of FAD-linked L-glycerol-3-phosphate dehydrogenase was dramatically influenced by thyroxine. PMID- 2917650 TI - The role of long-chain acyl-CoA in the damage of oxidative phosphorylation in heart mitochondria. AB - The aim of this investigation was to study the effect of intramitochondrial acyl CoA on the respiration of rabbit heart mitochondria over the whole range of stationary respiratory rates between States 4 and 3. The creatine phosphokinase system was used for stabilization of extramitochondrial adenine nucleotide concentration. It was shown that acyl-CoA depressed respiration more effectively in the intermediate range of respiration between States 4 and 3. The effect of acyl-CoA was negligible near State 4 and in State 3. These data are in line with our previous results concerning the dependence of the adenine nucleotide translocator control coefficient on the rate of mitochondrial respiration. Thus, our data suggest that long-chain acyl-CoA may regulate oxidative phosphorylation in heart mitochondria in vivo. PMID- 2917651 TI - 1,2-sn-diacylglycerol accumulates in choline-deficient liver. A possible mechanism of hepatic carcinogenesis via alteration in protein kinase C activity? AB - Choline deficiency is associated with triacylglycerol accumulation in the liver, and is the only nutritional state known to trigger hepatic cancer spontaneously. In two different experiments, rats were pair-fed for 6 weeks with control (0.2% choline), or choline-deficient (CD) (0.002% choline) diets. Hepatic choline and phosphocholine declined in CD animals to 54% and 16% of control levels, respectively. In control livers, 1,2-sn-diacylglycerol (1,2-sn-DAG) concentration was (in nmol/g wet wt) 144 (+/- 25; mean +/- SE); while in CD livers it was 792 (+/- 140) in the first experiment. In the second experiment the values were 375 (+/- 26) and 1147 (+/- 74), respectively. 1,2-sn-DAG, a precursor of triacylglycerol, is an endogenous activator of protein kinase C (PKC). PKC is the presumed site of action of the tumor-promoting phorbol esters. We suggest that the 1,2-sn-DAG accumulating in CD liver could bind PKC, altering its activity, and thus contribute to the carcinogenic effect of CD diets. PMID- 2917652 TI - A new heparin-inhibited and polyamine-activated protein kinase from bovine kidney. AB - Two casein kinases, casein kinase-1 (CK-1) and casein kinase-2 (CK-2), have been characterized from many sources. In this study we describe the properties of a third casein kinase, designated casein kinase-3 (CK-3). CK-3 (Mr 32,000) is readily separated from CK-2 by gel filtration and from CK-1 by hydroxyapatite chromatography. CK-3 phosphorylates several proteins, including phosphorylase kinase. Phosphorylation of phosphorylase kinase by CK-3 results in a 10-fold enzyme activation. CK-3 is activated by spermine and inhibited by heparin, ADP, and divalent metal ions (Mn2+, Zn2+). Heparin inhibition of the kinase is reversed by spermine. The physical and regulatory properties of CK-3 are very similar to CK-1, suggesting that these kinases may be closely related. PMID- 2917653 TI - Isoenzyme patterns of protein kinase C and a phospholipid-dependent but Ca2+ inhibited enzyme fraction in the crude extracts of different tissues. AB - We compared the protein kinase C isoenzyme patterns of crude extracts of rabbit brain, cerebellum, spleen, thymus and human and pig granulocytes. The isoenzymes were fractionated by hydroxyapatite chromatography and the protein kinase C activity was determined with a synthetic oligopeptide substrate. In the extracts of several tissues we also observed an enzyme fraction which was activated by phosphatidylserine + diacylglycerol but inhibited by Ca2+. PMID- 2917654 TI - Extracellular adenosine triphosphate activates phospholipase C and mobilizes intracellular calcium in primary cultures of sheep anterior pituitary cells. AB - In primary cultures of sheep anterior pituitary cells extracellular ATP (ED50 0.4 0.8 microM) stimulated efflux of 45Ca2+ from a slow-turnover intracellular pool. ADP was also effective whereas AMP and adenosine were not. The ATP effect was not due to cell permeabilization as 100 microM ATP did not elicit efflux of 2 deoxy[3H]glucose metabolites. This 45Ca2+ mobilization may be mediated by inositol trisphosphate, since ATP (ED50 1 microM) stimulated inositol phosphate generation. These results demonstrate P2-purinoceptors in sheep anterior pituitary cells which are coupled to phospholipase C activation and intracellular Ca2+ mobilization, and raise the possibility of a regulatory role for extracellular ATP in the anterior pituitary. PMID- 2917655 TI - Complement C9 is inserted into membranes in a globular conformation. AB - Complement component C9 undergoes a major conformational change during its insertion into a biological membrane from a globular to an extended form. At 0 degrees C a single C9 binds but a membrane attack complex (MAC) is not formed. We show that the C9 bound at 0 degrees is accessible to the intracellular space and sensitive to trypsin digestion, suggesting that C9 inserts in its globular state and requires an elevated temperature in order to change conformation. PMID- 2917656 TI - Unique substrate specificity and regulatory properties of PKC-epsilon: a rationale for diversity. AB - PKC-epsilon was isolated from a murine brain cDNA library. The clone, lambda 61PKC-epsilon, encoded a polypeptide of 737 amino acids that is homologous to other PKCs. Northern analysis showed that the 7 kb mRNA for this cDNA is widely expressed. The protein when expressed in COS-1 cells displayed phorbol ester binding activity. However in order to detect the kinase activity of PKC-epsilon, it was necessary to employ a synthetic peptide substrate based upon the pseudosubstrate site. Subsequent analysis demonstrated that PKC-epsilon, while showing certain properties characteristic of the PKC family, has a quite distinct substrate specificity and is independent of Ca2+. PMID- 2917657 TI - Localization of melted regions in supercoiled DNA. AB - Diethyl pyrocarbonate (DEPC) was used as a probe of local denatured regions in ccDNA pAO3 plasmid. It was found that in native ccDNA molecules only adenosine residues in the loop of the cruciform structure react with DEPC. Denaturation of ccDNA is accompanied by the appearance of two short regions (20 bp long) at both borders of the cruciform structure. Further increase in the denaturation process is associated with considerable expansion of the region located to the left of the cruciform, while the cruciform structure itself and the denatured region located to the right of it disappear. PMID- 2917658 TI - Two physiological substrate-specific casein kinases are present in the bovine mammary gland. AB - Two species of casein kinase from lactating bovine mammary gland have been identified; a Ca2+- and CM-independent casein kinase and a Ca2+- and CM-dependent casein kinase. The Ca2+- and CM-independent casein kinase phosphorylates previously dephosphorylated alpha s1-, beta- or kappa-casein while the Ca2+- and CM-dependent casein kinase prefers previously dephosphorylated beta- or kappa casein as substrates. Two activities are indicated by their substrate specificity, sensitivity to Ca2+ and CM, pH maxima, and differential solubilization by anionic detergents. The presence of a regulated casein kinase in the lactating mammary gland suggests that casein phosphorylation may be a regulator of micelle formation or secretion. PMID- 2917659 TI - Specificity of GDP-Man:dolichyl-phosphate mannosyltransferase for the guanosine diphosphate esters of mannose analogues containing deoxy and deoxyfluoro substituents. AB - Guanosine diphosphate (GDP) esters of 2-deoxy-D-glucose (2dGlc), 2-deoxy-2-fluoro D-mannose (2FMan), 3-deoxy-D-mannose (3dMan), 4-deoxy-D-mannose (4dMan) and 6 deoxy-D-mannose (6dMan) have been synthesised and tested for their ability to act as inhibitors of dolichyl phosphate mannose synthesis (enzyme: GDP mannose:dolichyl-phosphate mannosyltransferase, EC 2.4.1.83) in chick embryo cell microsomal membranes. The following order of efficiency was found with the apparent Ki in parentheses: GDP-6dMan (0.40 microM +/- 0.15) greater than GDP 3dMan (1.0 microM +/- 0.1) = GDP-2dGlc (1.3 microM +/- 0.2) greater than GDP 4dMan (3.1 microM +/- 0.1) GDP-2FMan (15 microM +/- 0). For comparison the Km for GDP-Man was 0.52 microM +/- 0.02 and the Ki for GDP was 56 microM +/- 2. These results indicate that the 6-hydroxyl group of mannose is not crucial for enzyme substrate recognition, whereas the 2- and 3-hydroxyls may have some involvement. The 4-hydroxyl appears to be an important determinant for enzyme-substrate recognition in this mannosyltransferase. PMID- 2917661 TI - A new instrument for bone drill biopsy. AB - Modern treatment of bone tumors requires more biopsies to be taken for diagnosis and evaluation of treatment. Two types of bone biopsy are distinguished: Open, and closed or drill biopsies. Both have advocates and adversaries. We describe a new instrument for drill biopsy which is easy to handle. PMID- 2917660 TI - Merkel cell carcinoma: management of primary, recurrent and metastatic disease. A clinicopathological study of 17 patients. AB - The clinicopathology of Merkel cell carcinoma (MC) has been evaluated in 17 patients, and its outcome and clinical management in 14 of these. The histopathologic diagnosis was confirmed by electronmicroscopy and/or immunohistopathology. The location of the primary lesions demonstrated a predilection for the skin of the face and the extremities. The primary treatment usually consisted of a wide excision only. Four out of five patients with MC of the face suffered from local and/or nodal relapses, in contrast to only one out of seven patients with primary lesion on the extremities. The three patients treated for local recurrences and/or regional node metastases were alive and disease-free 22-72 months after recurrences. Three patients developed distant metastases. Two of these died within 4 months after initial diagnosis. One patient completely responded to chemotherapy. The high frequency of local recurrences would justify an excision with generous margins, except when the tumour is close to a vital structure. Radiotherapy could in these cases obviate the necessity for extensive operations. If the primary lesion is located on an extremity, regional lymphadenectomy seems only to be necessary whenever nodal involvement is suspected. Node dissection is also recommended for suspected nodes in the face or on the neck, but the guidelines for elective node dissections in these sites are not obvious since the results of salvage therapy were excellent and the location of relapses unpredictable. PMID- 2917662 TI - Fine needle aspiration cytology in superficial lymph nodes: an analysis of 266 cases. AB - The results of fine needle aspiration cytology of superficial lymph nodes in 275 patients are discussed. Nine cases were lost to follow-up. Of the remaining 266 aspirates, 152 were classified as cytologically malignant, 79 as benign, three as suspicious for malignancy, and 32 as unsatisfactory owing to scanty cellularity. The sensitivity of cytology for metastatic cancer was 96.5%. The results of aspiration biopsy from lymphomas were less accurate (67.5% sensitivity). There were no false positives and nine (11.3%) false negatives. Open biopsy of three suspect lymph nodes proved them to be malignant. The aspiration procedure is easy, safe and reliable. The diagnosis of benignity cannot, however, be determined without an open biopsy, particularly for lymphomas. PMID- 2917663 TI - Histological grading of breast cancer; significance of grade on recurrence and mortality. AB - The influence of histological grade on the recurrence and mortality of patients with breast cancer is reported for 829 patients. The effect of the histological grade is also compared with the effect of axillary node involvement and the implications for clinical studies of the management of breast cancer discussed. The prognosis for both recurrence and death becomes increasingly poor as the degree of differentiation decreases, as reflected by the grading allocated to the tumour. This effect is independent of the clinical stage of the cancer at the time of treatment. PMID- 2917664 TI - Clinical response and survival according to estrogen receptor levels after bilateral ovariectomy in advanced breast cancer. AB - Estrogen receptor levels were determined at the time of ovariectomy in 71 premenopausal women with advanced breast cancer. Three groups of estrogen receptor concentration were established: less than 10 fmol/mg cytosol protein (group 1), between 10 and 25 fmol/mg cytosol protein (group 2), and more than 25 fmol/mg cytosol protein (group 3). The frequency of clinical response to ovariectomy was low in group 1 (17.4%), high in group 3 (79.4%), and intermediate in group 2 (35.7%). Median survival was poor in group 1 (18.5 months) and better in groups 2 (33.0 months) and 3 (32.5 months). These results were independent of disease stage and neoplastic localization. PMID- 2917665 TI - Thyroid cancer in children and adolescents in Denmark. AB - From 1960 to 1985, 20 patients (12 females and eight males) with thyroid cancer, developed before the age of 20, have been registered and observed at the Radium Center, The Finsen Institute. Papillary adenocarcinoma was diagnosed in 11 cases, and mixed papillary/follicular adenocarcinoma in six cases. Three patients had medullary carcinoma. No patients had previously received cervical irradiation. On admission, lung metastases were evident in two cases. All patients underwent surgical treatment, which in 15 cases consisted of total thyroidectomy, and in nine also lymph node dissection. External irradiation was given to 10 patients, and radioiodine treatment was performed in five patients. Local and/or distant relapse of the thyroid carcinoma occurred in five cases: three were patients with medullary carcinoma, and two had papillary and mixed adenocarcinoma. The three patients with medullary carcinoma died of their disease, but the other two with recurrence recovered after surgery, external irradiation and/or radioiodine treatment. Currently, 16 patients are alive without evidence of disease. The period of follow-up ranged from 2 to 23 years. PMID- 2917666 TI - Carcinoma of the uterine cervix stage I and IIA: results of surgical treatment: complications, recurrence and survival. AB - Between 1967 and 1981, 213 patients with carcinoma of the uterine cervix Stage I and IIA underwent an abdominovaginal radical hysterectomy with transperitoneal lymphadenectomy. In 1987 the overall 5-year survival rate was 87.5% and the 10 year survival 85%. Recurrences were seen in 29 patients (13.7%). Lymph node metastases occurred in 39 patients (18%). Five-year survival decreased from 94% without positive nodes to 65% with positive nodes. The median blood loss was 2100 cc. Fistulas were seen in 6.7% of the patients. Long-term voiding problems were encountered in 40.8%. In 25% of the women intercourse was impeded postoperatively because of shortening of the vagina. The results obtained with this type of radical surgery in cervical cancer Stages I-IIA are good and do not differ from other methods reported in the literature. However this also means that this more difficult and time-consuming approach does not improve survival rates. For this reason there are no reasons to change from the Wertheim operation to this combined approach. PMID- 2917667 TI - Experience with a totally implantable catheter in adult patients: a single institution retrospective study of 114 cases. AB - One hundred and fourteen consecutive totally implantable catheters were inserted in 114 patients between April 1984 and April 1987. Catheters were inserted under neuroleptanalgesia, through the jugular vein in 101 cases or the internal saphenous vein in 13 cases. No problem was encountered during the insertion procedure. Infection occurred in 5.2% of the patients but removal of the device was required in only 2.6%. Occlusion of the catheter occurred in 6.1% of the patients but never during the first 2 months. This complication rate is lower than the one observed with external tunnelled catheters. The comfort of the patient is substantially improved and nursing care is greatly facilitated. PMID- 2917669 TI - Adenocarcinoma cell invasion of an obturator artery aneurysm. AB - Classic teaching implies that arterial walls are a resistance to tumour invasion. We report a case of tumour cell infiltration of an obturator artery aneurysm following an abdomino-perineal excision of rectum. PMID- 2917668 TI - Epithelioid haemangioendothelioma of the liver: objective response to hepatic intra-arterial 5-FU. AB - A case of an epithelioid haemangioendothelioma of the liver is presented. The tumour was unresectable at laparotomy because of extensive involvement of both lobes of the liver. The histological appearances of the biopsy taken at operation suggested that the lesion was at the more malignant end of the spectrum for these tumours. The patient was treated by cycles of hepatic intra-arterial 5 fluorouracil with relief of symptoms and prolonged survival. It is important to recognize this type of neoplasm which bears resemblance to other liver pathologies, in particular, to sclerosing cholangiocarcinoma. PMID- 2917671 TI - Late onset of pectoralis major wasting after Patey mastectomy. PMID- 2917670 TI - Quantitative profiling of faecal bile acids in experimental colorectal cancer. PMID- 2917672 TI - Animal bite infections. PMID- 2917673 TI - The Medical Center of Delaware infectious disease clinic. PMID- 2917674 TI - The care of AIDS patients in Delaware. PMID- 2917675 TI - Infections due to coagulase-negative staphylococci. PMID- 2917676 TI - Influence of topically applied betamethasone-17-valerate on cell cycle kinetics of human anagen hair determined by DNA flow cytometry. AB - In 47 healthy volunteers betamethasone-17-valerate (0.1% solution and cream) was topically applied twice daily on the scalp skin. After 7 and 14 days treatment, anagen hairs were plucked in each volunteer from both treated and untreated contralateral scalp areas. Cell cycle analysis of plucked anagen hairs was performed by means of DNA flow cytometry. Already after topical betamethasone-17 valerate application for 7 days, cell kinetic changes were found showing a slightly significant decrease of S and G2 + M cell percentages and a significant increase of G0/1 cell percentages. The present study demonstrates the possibilities of DNA flow cytometry to study the pharmacological effects on cell kinetics of plucked human anagen hairs. PMID- 2917677 TI - The Muir-Torre syndrome: a disease of sebaceous and colonic neoplasms. AB - The Muir-Torre syndrome of sebaceous neoplasms of the skin, with or without keratoacanthomas, and multiple low-grade visceral malignancies with prolonged survival is a rare disorder. Colonic polyps are frequently present, and the syndrome appears to be familial. We report 2 unrelated patients with the Muir Torre syndrome. Each case exhibited sebaceous adenomas. Gastrointestinal findings included colonic adenocarcinomas and a tubulovillous adenoma. Although an unusual disease, the Muir-Torre syndrome requires recognition because these patients are at risk for multiple primary malignancies and may have family members also at risk. PMID- 2917678 TI - Pemphigus vulgaris following cobalt therapy for bronchial carcinoma. AB - A 52-year-old male patient with bronchial carcinoma developed pemphigus vulgaris 3 weeks after the end of cobalt therapy. The possible role of gamma-radiation in inducing the skin disease is discussed. PMID- 2917679 TI - An unusual combination of phototoxicity and Stevens-Johnson syndrome due to antimalarial therapy. AB - A 12-year-old boy developed a phototoxic rash with subsequent progression to Stevens-Johnson syndrome due to prophylactic ingestion of antimalarials (chloroquine and sulfadoxine-pyrimethamine; Fansidar). The patient recovered from his skin symptoms after 4 weeks during which he received systemic corticosteroids and antibiotics. This unusual combination of two different patterns of adverse cutaneous drug reactions was most probably caused by the sulfonamide component of Fansidar. PMID- 2917680 TI - Skin necrosis due to intravenous heparin. AB - A patient on intravenous heparin is described who developed an acute hemorrhagic necrosis of her legs. Thrombi without vasculitis were seen in the dermal blood vessels. This appears to be the 4th reported case of skin necrosis after intravenous heparin at sites unrelated to injections. Skin necrosis after intravenous heparin should warn the dermatologist of a possible fatal outcome from myocardial or cerebral infarction. PMID- 2917681 TI - Atopic dermatitis flare provoked by inhalant allergens. AB - We report on 2 patients with atopic dermatitis (AD) exacerbated by inhalant allergens: grass pollens in spring (AD as hay fever equivalent) and nonbiting red midges (chironomides) in pet fish food. These clinical observations confirm the existence of an 'extrinsic', IgE-mediated type of AD in a minority of patients, in which the IgE sensitization against specific allergens plays a causal role for the skin disorder. PMID- 2917682 TI - Dermatomyositis-like syndrome induced by nonsteroidal anti-inflammatory agents. AB - A dermatomyositis-like syndrome developed in a patient treated with a nonsteroidal anti-inflammatory agent (NSAI), niflumic acid, and regressed after the cessation of treatment. Previously an eruption had occurred under treatment with another NSAI, diclofenac. Our report shows that NSAI can induce not only lupus-like syndromes but also other connective tissue disorders. PMID- 2917683 TI - Pemphigus--an atavism? PMID- 2917684 TI - Regulation of liver angiotensinogen mRNA by glucocorticoids and thyroxine. AB - This study examines the immediate and longer-term changes in angiotensinogen mRNA and in plasma angiotensinogen which follow the withdrawal and replacement of glucocorticoids or thyroxine. RNA from rat liver was analysed by Northern blot and dot-blot hybridization with a 40-mer oligodeoxynucleotide probe specific for angiotensinogen mRNA. Adrenalectomy decreased plasma angiotensinogen and angiotensinogen mRNA to 55 and 50% of control values respectively over a period of 16 days. Similar decreases were obtained after propylthiouracil (1 mg/kg for 16 days) treatment, except when injected simultaneously with T3 (3 micrograms/kg/day). Over the same period plasma renin activity increased in adrenalectomized rats from 4.1 +/- 0.8 to 7.0 +/- 1.5 pmol angiotensin I (AI)/ml/h, and decreased in propylthiouracil-treated rats from 3.8 +/- 0.4 to 1.6 +/- 0.4 pmol AI/ml/h. Approximate half-times of 2-3 days were calculated for both plasma angiotensinogen and angiotensinogen mRNA post-adrenalectomy or after propylthiouracil treatment. Dexamethasone (400 micrograms/kg, i.m.) given to intact rats rapidly increased angiotensinogen mRNA to a maximum of 250% of control by 8 h and with a half-maximal response of 2.8 h. Plasma angiotensinogen responded similarly, apart from an initial delay of 2 h. Treatment with different doses of propylthiouracil and dexamethasone showed that responses were dose related. We conclude that changes in plasma angiotensinogen and angiotensinogen mRNA are closely correlated, and that under various physiological circumstances angiotensinogen mRNA has a rapid rate of accumulation but a slow rate of decay. PMID- 2917685 TI - Production and secretion of the 21-23.5 kDa prolactin-like molecules. AB - We recently described the presence of a series of prolactin (PRL)-like molecules (PLMs) in the rat pituitary gland and showed that their formation was not due to artifactual proteolysis of 24 kDa PRL during extraction or to degradation of PRL in lysosomes. In this study we have found (1) in vitro translation of pituitary cell RNA to result in the production of only 24 kDa monomer isoform 2 and no PLMs, (2) that secretion of newly synthesized PLMs is differently regulated than at least a proportion of newly synthesized monomers, (3) that secretion of newly synthesized PLMs occurs after at least a 6 h delay, (4) that cysteamine (a) inhibits the release of the PLMs, (b) causes an increase in their amount versus isoform 2, and (c) causes an intracellular accumulation of pleiomorphic, immature secretory granules, and (5) that cells grown under degranulating culture conditions do not contain PLMs. These results, using normal anterior pituitary cells in primary culture, demonstrate the potential for differential release of the PLMs versus monomer PRL in vivo and are consistent with the production of the PLMs from 24 kDa monomer isoform 2 during secretory granule condensation. PMID- 2917687 TI - Human choriogonadotropin entrapped into liposomes: characterization, biologic effects and interaction with purified mouse Leydig cells in vitro. AB - Liposomes containing human choriogonadotropin (hCG) were prepared from phosphatidylserine by the ether injection method. hCG adsorbed to the outer surface of the liposomes (77% of total liposome-associated hCG) was removed by proteolytic digestion with subtilisin. hCG-containing liposomes digested and not digested with subtilisin stimulated testosterone biosynthesis by Leydig cells in a dose-dependent way; both preparations had identical biologic activities (32% of the activity of free, not liposome-associated hCG) when equal doses of liposome associated hCG were applied. The onset of stimulation was delayed when compared to the action of free hCG. Liposomes without hCG did not stimulate testosterone biosynthesis. Association of liposomes with Leydig cells was determined by measurement of transfer of radioactive label from liposomes to Leydig cells. The association was not mediated by the hormone receptor. hCG entrapped in liposomes was incorporated by Leydig cells and translated to the cellular surface. This process was impaired by colchicine (10(-5) M). hCG translocated to the external surface of the cell membrane contained a modified alpha-subunit (Mr 16,200 instead of 20,600) which was not detected in unentrapped hCG bound to Leydig cells. We suggest that liposomally entrapped hCG is taken up by Leydig cells and re-exported to the cell membrane by a mechanism resembling retroendocytosis. PMID- 2917686 TI - Peroxisomal oxidative capacity of brown adipose tissue depends on the thyroid status. AB - The induction of hypothyroidism in rats by methimazole affects interscapular brown adipose tissue (IBAT) mitochondrial and peroxisomal enzyme activities in opposite directions. Hypothyroidism, indeed, decreases both mitochondrial succinate dehydrogenase and beta-oxidation total activities by 35 and 45%, respectively and increases peroxisomal catalase and acyl coenzyme A (acyl CoA) oxidase total activities 3.2- and 1.6-fold, respectively. Administration of a thyroid hormone analogue (3'-isopropyl-3,5-diiodo-L-thyronine) prevents these enzymatic modifications. The effects of hypothyroidism on IBAT mitochondrial enzyme activities seem to be direct, i.e. due to the lack of thyroid hormones, while those on peroxisomal enzyme activities might be indirect, i.e. secondary to the increased thermogenic needs of the rat and mediated by adrenergic stimulation. It is noteworthy that the indirect effects of hypothyroidism on peroxisomes are not observed in liver where acyl CoA oxidase activity is in fact decreased by 40%. In hypothyroid rat IBAT, administration of the peroxisome proliferator nafenopin does not further stimulate the already increased peroxisomal enzyme activities and does not inhibit the already decreased mitochondrial enzyme activities. PMID- 2917688 TI - The N-terminal domain of the human androgen receptor is encoded by one, large exon. AB - Using specific cDNA hybridization probes, the first coding exon of the human androgen receptor gene was isolated from a genomic library. The exon contained an open reading frame of 1586 bp, encoding an androgen receptor amino-terminal region of 529 amino acids. The deduced amino acid sequence was characterized by the presence of several poly-amino acid stretches of which the long poly-glycine stretch (16 residues) and the poly-glutamine stretch (20 residues) were most prominent. Androgen receptor cDNAs from different sources contained information for poly-glycine stretches of variable size (23 and 27 residues, respectively). The androgen receptor amino-terminal domain was found to be hydrophilic and have a net negative charge. Combined with the previously described, partially overlapping cDNA clone 7A2M27 (Trapman et al. (1988) Biochem. Biophys. Res. Commun. 153, 241-248), the complete human androgen receptor was deduced to have a size of 910 amino acids. PMID- 2917689 TI - Developmental stage-specific antigens in the nervous system of the cockroach. AB - A specific effort was made to obtain monoclonal antibodies that bind to macromolecules that play a role in the development of the nervous system. It was considered that good candidates for such molecules were those that were only transiently present in the embryonic nervous system. Hybridomas were prepared from spleen cells taken from mice that had been immunized with nerve cords from cockroach embryos at the 43-50% stage of development. The hybridoma supernatants were screened for antibody binding to frozen sections of both embryonic and adult thoracic ganglia. Cell lines that produced monoclonal antibodies that transiently bound to the embryonic nervous system were saved and cloned. These developmental stage-specific monoclonal antibodies either did not bind to the adult nervous system or bound to it with a pattern very different from that in the embryonic nervous system. The developmental stage-specific antigens detected by these monoclonal antibodies were organized into four categories based on the part of the embryonic nervous system in which they were transiently localized. These include binding to the cell bodies of all neurons, cell bodies of subsets of neurons or neuroblasts, subsets of axons, and the neuropile. Preliminary biochemical characterization of the antigens showed that many of these antibodies were recognizing carbohydrate epitopes. Functions for these antigens, most of which are components of the cell surface, are tentatively proposed. PMID- 2917690 TI - Nerve and muscle development in paralyse mutant mice. AB - Nerve and muscle development was studied in paralyse mutant mice. The mutant phenotype is first recognizable 6-7 days after birth (PN 6-PN 7) as cessation of muscle growth and weakness and incoordination of movement. Mutant animals die between 2 and 3 weeks of age. Muscle fibers from paralyse mutants had a unimodal distribution of diameters and normal numbers and distributions of acetylcholine receptors. The only structural abnormality seen was a reduced extracellular space within muscle fascicles. Total muscle choline acetyltransferase activity was reduced compared with that of control muscles, indicating that synaptic terminal development was impaired. Light and electron microscopy showed that polyneuronal innervation was retained in mutant endplates, and the normal process of withdrawal of redundant innervation did not occur. The paralyse muscles reacted to experimental denervation with an increase in extrajunctional acetylcholine receptor numbers. Intramuscular axons failed to become myelinated in mutant animals, although sciatic nerve axons were myelinated with a normal myelin thickness/axon diameter ratio. Nodes of Ranvier were elongated and myelin lamellae in the paranodal regions were poorly fused. Sciatic nerves in mutant animals retained the neonatal unimodal distribution of axon diameters, whereas in control animals it became bimodal by 2 weeks of age. Our results are not consistent with a previous suggestion that paralyse mutant muscle endplates are progressively denervated. We conclude that the major expression of the paralyse mutant phenotype is an arrest in development of both nerve and muscle during the first week after birth. The paralyse mutant gene most likely is involved in the general support of development of many or all body tissues from 1 week of age. We found no regression of any aspect of differentiation, once achieved. PMID- 2917691 TI - Developmental regulation of energy metabolism in Caenorhabditis elegans. AB - Changes in energy metabolism during larval development in Caenorhabditis elegans have been investigated using phosphorus nuclear magnetic resonance (31P NMR). The relative concentrations of ATP, ADP, AMP, sugar phosphates, and other metabolites were observed to change during larval development, producing stage-specific spectra. These spectra are consistent with enzyme assays for isocitrate dehydrogenase and isocitrate lyase, indicating that high activity of the glyoxylate pathway during embryonic development decreases during the first larval (L1) stage, and respiration during the L2, L3, and L4 stages occurs preferentially through the TCA cycle. Metabolic strategies were further studied using mutants that are predisposed to enter the dauer stage, a developmentally arrested third-stage larva formed under conditions of overcrowding and limited food. After the L1 molt, energy metabolism in animals destined to become dauer larvae diverges from that of animals committed to growth. Relative to the L1, the L2 larvae committed to growth exhibit increased isocitrate dehydrogenase activity as well as increases in ATP and other high-energy phosphates, but predauer (L2d) larvae exhibit declining enzyme activities and declining levels of high-energy phosphates. The predominant phosphorus NMR signal in dauer larva extracts corresponds to inorganic phosphate. We conclude that metabolism is regulated during C. elegans larval development, with a major transition apparent after the L1 stage. This transition does not occur in larvae destined to form dauer larvae. PMID- 2917692 TI - Relationship between the M42 antigen of mouse sperm and the acrosome reaction induced by ZP3. AB - A murine monoclonal antibody, M42 mAb, directed against 200/220 Kd protein of mouse sperm, has been employed to study the molecular events of gamete interaction. We have reported previously that M42 mAb blocks mouse fertilization in a zona-dependent manner; the reagent specifically inhibits physiologically induced (zonae), but not pharmacologically induced (A23187), acrosome reactions in mouse sperm. Using solubilized mouse zonae pellucidae and purified ZP3, we demonstrate that M42 mAb inhibits acrosome reactions (ARs) induced by ZP3 to the same extent as those induced by total zonae. We have also studied AR inhibition using the fluorescent antibiotic chlortetracycline (CTC), which permits visualization of three different acrosomal patterns during the AR. In the presence of M42 IgG, greater than 70% of capacitated sperm treated with zonae are arrested in the acrosome-intact state (B-pattern), in contrast to the majority of sperm (60-70%) in the absence of M42 IgG, which progress through the intermediate phase (S-pattern) to the fully acrosome-reacted (AR-pattern) state. Incubation of sperm with zona proteins modified by incubating eggs with phorbol esters arrests sperm in the S-pattern (Y. Endo, R.M. Schultz, and G.S. Kopf, 1987, Dev. Biol. 119, 199-209). We show that once sperm have reached such a state, M42 mAb no longer exerts an inhibitory effect. The addition of unmodified ZP to S-pattern sperm permits the completion of the acrosome reaction. These results indicate that M42 mAb blocks an early step in the AR cascade and that M42 mAb is unable to prevent subsequent events of this cascade once it has been initiated. PMID- 2917693 TI - Electrophoretic repatterning of charged cytoplasmic molecules within tissues coupled by gap junctions by externally applied electric fields. AB - Ionic currents and cytoplasmic voltage gradients have been observed in a variety of polarizing cells and developing tissues. In certain cases, it has been determined that these endogenous electric fields can segregate intracellular charged molecules by electrophoresis; in other cases, the endogenous fields are suspected to have such an influence. Separate theoretical suggestions have been made that extracellular electric currents, whether from a biological or a nonbiological source, should be able to electrophorese intracellular molecules after being conducted through cell membranes into the interior of long single cells [L.F. Jaffe and R. Nuccitelli (1977) Annu. Rev. Biophys. Bioeng. 6, 445 476] or extended ensembles of cells coupled electrotonically by gap junctions [M.S. Cooper (1984) J. Theor. Biol. 111, 123-130]. To test whether external electric fields could redistribute intracellular molecules within a tissue coupled by gap junctions, and to quantitatively measure in situ the electrophoretic mobility of a charged intracellular molecule, we injected 6 carboxyfluorescein into the electrotonically coupled lateral giant neurons of the crayfish abdominal nerve cord. When a dc electric field (0.2-3.4 V/cm) was subsequently applied along the length of the cord, the negatively charged fluorescent dye was observed to migrate through both the cytoplasms and the gap junctions of the lateral giant neurons, toward the anode, at a rate directly proportional to the applied electric field strength (electrophoretic mobility = 0.92 +/- 0.27 micron/sec per V/cm). These results suggest that electric fields of a sufficient magnitude, whether of an exogenous or an endogenous origin, can repattern the distribution of charged molecules within the cytoplasm of an extended ensemble of coupled cells. In addition, these results suggest that externally applied electric fields might be used in studies of pattern formation to repattern the intercellular distribution of charged molecules that are permeant to gap junctions within electrically coupled tissues. PMID- 2917694 TI - Development of Iiyanassa obsoleta embryos after equal distribution of polar lobe material at first cleavage. AB - Ilyanassa obsoleta embryos cleave unequally via the formation of polar lobes, which contain materials essential for the development of larval shell, foot, operculum, statocysts, and eyes. Polar lobe material is shunted to the CD cell during first cleavage and to the D cell during second cleavage. Treatment with cytochalasin B (CB) before first cleavage prevents the formation of the polar lobe and leads to equal cleavage and the equal distribution of lobe material. At second cleavage each cell forms a polar lobe, resulting in a four-cell stage with two large (D) cells and two smaller (C) cells. Embryos equalized with CB frequently display duplications, 68% duplicating two or more larval structures. Embryos with adjacent D cells (CCDD) duplicate statocysts more frequently than embryos with opposite D cells (CDCD), perhaps due to enhanced inductive interactions. When equal cells are separated after first cleavage, resulting larvae develop like CD halves from control embryos. When equal halves are analyzed as pairs and compared with whole, equalized embryos, they duplicate shell, foot, and operculum more frequently. This difference is probably due to masking of duplications of these structures in whole, equalized embryos rather than to general inhibitory interactions between the two D quadrants. These results are discussed with respect to proposals that interactions between D quadrants in equalized embryos may alter developmental capabilities. PMID- 2917695 TI - Gradual appearance of a regulated retinotectal projection pattern in Xenopus laevis. AB - The topographic projection pattern formed by the retinal ganglion cell axons in the tectum of the lower vertebrate appears to require positional cues that guide the optic nerve fibers to their appropriate targets. One approach to understanding these positional cues or "positional information" has been to investigate changes in the pattern of the retinotectal projection after surgical manipulation of the embryonic eyebud. Analysis of these apparent changes in the patterns of positional information in the eye, termed "pattern regulation," may provide clues to both the nature of positional information and the mechanisms by which it is assigned to cells in the eyebud. Here we examine pattern regulation in the Xenopus visual system following the replacement of the temporal half of a right eyebud with the temporal half of a left eyebud. This manipulation requires that the left half-eyebud be inverted along its dorsoventral axis. Electrophysiological maps of these compound eyes in postmetamorphic frogs reveal regulated maps; the cells in the temporal half of the NrTl eye project to the tectum with a dorsoventral polarity appropriate for their position in the host eye and not appropriate for the original positions of the grafted cells in the donor eyebud. Paradoxically, the regulated patterns are not apparent in the projections of the original grafted eyebud cells during early larval development. Using fiber-tracing and electrophysiological mapping techniques, we now show that the regulated patterns appear gradually in the projections made by peripheral retinal cells added during mid-larval development. Because the regulation occurs relatively late in development and probably only in the peripheral retinal cells, simple models of epimorphic or morphallactic regulation do not appear to fit this system. Thus, new or more complex models must be invoked to explain the phenomenon of pattern regulation in the developing visual system of Xenopus. PMID- 2917696 TI - Expression of an embryonic spicule matrix gene in calcified tissues of adult sea urchins. AB - The sea urchin spicule is composed of CaCO3 associated with an organic matrix containing at least 10 proteins. We have previously shown that one of these proteins, a 50-kDa glycoprotein (SM 50), is encoded by a gene which is only transcribed in cells of the micromere-mesenchyme lineage. In this report we examined RNA from five adult tissues: ovary, coelomocytes, intestine, tube feet, and spine for the presence of SM 50 transcripts and protein. Only RNA from cells of spine and tube feet hybridized to a SM 50-specific probe on Northern blots. These same two tissues undergo biomineralization and contain a protein which is immunologically related to the SM 50 protein. The restricted accumulation of SM 50 transcripts and protein suggests that the differentiation of biomineralizing mesenchyme cells in embryonic and adult tissue may utilize the same genetic program. PMID- 2917697 TI - Developmental and muscle-specific changes in methylation of the myosin light chain LC1f and LC3f promoters during avian myogenesis. AB - The fast alkali myosin light chains LC1f and LC3f are two contractile protein isoforms encoded for by a single gene complex. Expression of these two isoforms is dependent upon differential initiation of transcription at either of two promoters encoding unique 5' exons for isoform-specific amino termini of these light chains. Studies of protein expression have shown that the two isoforms are first expressed at different stages of development and in the case of the LC3f isoform only in fast twitch muscle fiber types. The molecular mechanisms that regulate the differential transcription of the gene complex are unknown. Experiments reported here demonstrated the direct correlation of isoform protein and mRNA expression with the undermethylation of the DNA in the promoter regions of the gene for each of the expressed myosin light chain isoforms. We find that fast and slow muscles have different patterns of undermethylation of the two promoter regions of the gene. Moreover, changes in methylation of the promoter regions were shown to occur specifically in skeletal muscle tissue, to be developmentally regulated, and to only occur in the LC3f promoter of those muscle groups that express LC3f protein. PMID- 2917698 TI - Dorsalization of mesoderm induction by lithium. AB - Lithium dorsalizes the body plan of Xenopus embryos when administered at the 32 cell stage (K.R. Kao and R.P. Elinson, 1988, Dev. Biol. 127, 64-77). In this paper, we have attempted to determine the effects of lithium on mesoderm induction, in order to localize the target of action of lithium. In the 32-cell embryo, the vegetal-most tier 4 cells are able to induce dorsal development in the overlying, equatorial tier 3 cells (R.L. Gimlich and J.C. Gerhart, 1984, Dev. Biol. 104, 117-130). Our experiments show that microinjection of lithium into either tier 3 or tier 4 cells of ultraviolet-irradiated, dorsoanterior-deficient embryos rescues normal development. Lineage tracer studies show that only tier 3 injected cells contribute progeny to dorsal axial structures while tier 4 injected cells contribute progeny to endoderm. Sandwich explants between animal caps and ventral vegetal cells cause induction of large amounts of muscle in the explants if either caps or vegetal cells are pretreated with lithium. Similarly, fibroblast growth factor-mediated mesoderm induction is also modified by lithium so that muscle is induced instead of ventral mesoderm. We conclude that lithium dorsalizes the response of animal cells to mesoderm induction signals, while not acting directly as a mesoderm inducer itself. The target of action of lithium is likely the third tier of cells of the 32-cell embryo. PMID- 2917699 TI - Diabetic myocardial infarction. Interaction of diabetes with other preinfarction risk factors. AB - To assess the effect of diabetes on outcome after acute myocardial infarction (MI), we compared a cohort of 228 type II (non-insulin-dependent) diabetic patients who had sustained acute MI with a similar number of nondiabetic patients with MI. Thirty-day mortality was greater in the diabetic group (27 vs. 17%). However, diabetic patients were older and had more cardiovascular disease before MI. Analyses accounting for such baseline risk revealed a complex effect of diabetes. The relative risk (RR) of dying from MI due to diabetes was greatest among patients with lowest baseline risk (RR 7.3) and least among those at highest baseline risk (RR 0.83). These effects were most striking with transmural MI, which was highly lethal for those with diabetes. Analyses with pulmonary edema as the endpoint support the significant risk conferred by diabetes and its interaction with baseline risk. Diabetes is a risk factor for poor outcome after MI, particularly among patients whose pre-MI cardiovascular status otherwise appears normal. PMID- 2917700 TI - Radioassay determination of insulin autoantibodies in NOD mice. Correlation with increased risk of progression to overt diabetes. AB - In an initial cross-sectional study, 29 female and 25 male nondiabetic weaned nonobese diabetic (NOD) mice of various ages (age range 30-300 days, mean 108 +/- 10 days) and 11 unweaned NOD pups were evaluated for competitive insulin autoantibodies (CIAAs) with a fluid-phase radioassay. Eleven of 54 (20%) weaned NOD mice had CIAA levels above the range (greater than 39 nU/ml) of 81 control mice. The group of NOD mice that progressed to diabetes had a significantly higher level of CIAAs than NOD mice that did not progress to diabetes (NOD mice progressing to diabetes: CIAA 63 +/- 12 nU/ml; NOD mice not progressing to diabetes: CIAA 8 +/- 4 nU/ml; P less than .02). Seven of 11 (64%) NOD mice having CIAA concentrations exceeding the normal range progressed to diabetes, whereas only 4 of 43 (9%) NOD mice progressed to diabetes without detection of elevated CIAAs (Fisher's exact test, P less than .0005). The relative risk of progressing to overt diabetes with CIAA levels greater than 39 nU/ml was therefore 17 (P less than .005), giving a positive predictive value of 64%, a negative predictive value of 91%, and an overall accuracy of 85%. None of 11 unweaned NOD pups had CIAA levels above the normal range (mean -9.4 +/- 4.9 nU/ml). At 6 wk of age, 37% of female NOD mice were CIAA+, whereas none of the male animals exceeded the normal range at this age (38 +/- 13 vs. 5 +/- 6 nU/ml, P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2917702 TI - [The status of computerized tomography in the diagnosis of primary cervix cancer]. AB - 172 patients with a primary cervical carcinoma have been examined using computerized axial tomography. CT-diagnosis was then analysed and compared with the results of the gynecological examination, cystoscopy, rectoscopy, lymphography, conventional radiological examination procedures and histology. CT is unsuitable for the primary diagnosis of cervical carcinoma and anyway unnecessary. In the case, where the carcinoma expands to the vagina, the diagnosis is quicker and more exact through inspection, palpation and biopsy rather than through CT. Moreover, to exclude a possible expansion of the carcinoma to the bladder and rectum, it is necessary that cystoscopy, rectoscopy as well as colon enema be performed. These examination procedures are in this case more effective than CT. Using CT, it is not feasible either to diagnose correctly the degree of infiltration of the parametria or to make definite predictions on the siting and operability. It is not necessary to use CT as a primary means of judging lymph node status, since other findings relevant to therapy (infiltration of the parametria, bladder, rectum) cannot be undertaken simultaneously with adequate safety. The use of CT in the diagnosis of the primary cervical carcinoma is therefore only of minimal importance. PMID- 2917701 TI - Gemfibrozil alone and in combination with lovastatin for treatment of hypertriglyceridemia in NIDDM. AB - Hypertriglyceridemic patients with non-insulin-dependent diabetes mellitus (NIDDM) have an increased risk of coronary heart disease (CHD) and acute pancreatitis. To examine the potential of hypolipidemic drugs for therapy of lipoprotein abnormalities in NIDDM, 10 patients maintaining marked (plasma triglycerides greater than 500 mg/dl) and 6 with moderate (plasma triglycerides 250-500 mg/dl) hypertriglyceridemia, despite good glycemic control, were studied in two phases. In the first phase, gemfibrozil alone (600 mg twice daily) was compared with a placebo, and in the second phase a combination of gemfibrozil and lovastatin (20 mg twice daily) was compared with gemfibrozil alone in a randomized, double-blind, placebo-controlled crossover study. In markedly hypertriglyceridemic patients, gemfibrozil reduced plasma triglycerides by 52% and very-low-density lipoprotein cholesterol (VLDL-chol) by 55% and increased high-density lipoprotein cholesterol by 23% compared with a placebo. However, low density lipoprotein cholesterol (LDL-chol) levels increased (42%), and LDL apolipoprotein B (apoB) levels remained unchanged. Addition of lovastatin to gemfibrozil effectively reduced total cholesterol (25%), LDL-chol (30%), and LDL apoB (19%). Lovastatin further reduced plasma triglycerides (11%) and VLDL-chol (27%). However, in moderately hypertriglyceridemic patients, gemfibrozil or the combination therapy did not seem to offer benefits over the previously reported study with lovastatin alone. Glycemic control was maintained throughout the study. In conclusion, the beneficial effects of the combination therapy on lipoprotein levels in markedly hypertriglyceridemic NIDDM patients could decrease the risk of development of both acute pancreatitis and CHD. PMID- 2917703 TI - [Intra-tubal embryo transfer. A new therapy in andrologic sterility]. AB - The intratubal transfer of pronucleus or early cleavage stage embryos (2-8-cell stage) is a new method in the treatment of human infertility. Following transvaginal sonographic oocyte retrieval, in vitro fertilization is performed and the fertilized oocyte pronucleus-stage or embryos are transferred into the tube by laparoscopy. By comparison to GIFT (intratubal gamete transfer), fertilization under in vitro conditions offers the advantage that the success of the fertilization process can be examined. Therefore, this method can give important diagnostic information--especially in cases of poor sperm quality or unexplained infertility. After fertilization in vitro and transfer into the tube the embryonic development occurs in the physiological milieu of the oviduct. Up until the present, the new procedure was performed in 40 patients with male factor or unexplained infertility. In 11 cases (28%) a pregnancy could be achieved. One abortion, but no ectopic pregnancy was observed. No difference in the pregnancy rates could be observed between the transfer of pronucleus stage and the early cleavage stage embryos. This method combines the advantages of IVF and GIFT and offers a successful procedure for the treatment of infertility. PMID- 2917704 TI - [Possibilities for using the LH color test in determining ovulation time]. AB - The LH color test was used to monitor 40 cycles of 32 patients. The urine test, which becomes positive at a LH-concentration of at least 50 I. U./ml, indicated the LH-peak in 34 out of 35 cycles with ascertained ovulation. In 24 cycles, the urine LH-peak preceded the serum LH-peak by one day. The urine LH-peak was found on cycle day 13.6 on average. The serum LH-peak on day 14.2 on average. The sensitivity of the LH color test was 97.2%, its specificity 100%. PMID- 2917705 TI - [Clinical and radiologic findings before and following sling operation for recurrent incontinence]. AB - In recent years, accurate preoperative diagnosis has been increasingly emphasized as an important therapeutic aspect of urinary incontinence in women. One of the diagnostic modalities employed is the lateral urethrocystogram. 25 patients with recurrent stress induced urinary incontinence were subjected to a dura-sling operation. The median duration of incontinence-related problems until secondary surgery (loop surgery) was 2.6 years. Radiological investigations before and after loop surgery showed, that this operation produces good morphological results, if the preoperative diagnosis is accurate. In 84% of the patients the continence obtained was verified by clinical evidence and radiologic findings. PMID- 2917706 TI - [Smoking and gestosis: comparative results of clinical and histomorphometric studies]. AB - Altogether 85 term placentae (20 from gestosis patients, 44 from patients who smoke and 21 normal term placentae) were examined macroscopically, microscopically and autoradiographically. The results and clinical data were analysed: strong smokers were compared with severe gestosis patients. A direct relation between reduced birthweight and placental insufficiency in gestosis patients and smokers could be established. In gestosis patients we found a "negative"--hypotrophic structural change of the placenta as a result of haemodynamic disturbance. In patients who smoke we found a "positive"- hypertrophic structural change of the placenta as an adaptation and compensation to the hypoxic stimulus of nicotine. PMID- 2917707 TI - [Immunotherapy following habitual abortion in paternal chromosome translocation]. AB - In a 41-year-old VII-gravida, I-para, the husband's reciprocal translocation of the chromosomes 1 and 18 as well as a partial identity of the marital partner in the HLA-system may have been the underlying causes for five abortions. In the 7th pregnancy, a prenatal chromosome analysis was performed as well as an immunotherapy with paternal lymphocytes, when uterine bleeding occurred. After termination of bleeding, the pregnancy continued without any complication. Our case report demonstrates the importance of an extensive search for causes leading to recurrent abortions not only with regard to diagnosis but also with regard to therapy in pregnancy. PMID- 2917708 TI - [Immunohistochemical and serologic detection of Ca-125 in patients with peritoneal tuberculosis and ascites]. AB - We report on two young patients with massively elevated CA-125 serum level of 290 and 264 U/ml respectively, who clinically exhibited suddenly occurring ascites. The diagnosis of ovarian carcinoma or ruptured ovarian cystoma led to a laparotomy. During the operation, a disseminating granulomatous inflammation was evident, which was identified histologically and microbiologically as miliary tuberculosis with peritoneal invasion. CA-125 was immunohistochemically localised, sharply demarcated around the tuberculous granuloma. A possible explanation for this finding is the inflammatory mesothelial proliferation. A similarity in antigenic structures of membrane components of M. tuberculosis and CA-125 cannot be excluded. Serum CA-125 levels tested 6 months after the treatment of the tuberculosis showed a value within the normal range (less than 35 U/ml). PMID- 2917709 TI - [Unusual course of metastatic cancer of the uterine cervix]. AB - The following report describes the case history of a 40-year-old woman suffering from a squamous carcinoma of the cervix uteri stage IV with predominantly cutaneous metastases. After a combined treatment of local radiotherapy and polychemotherapy with cisplatinum, bleomycin and methotrexate, a complete remission of the disease has been achieved. Six months later, however, a local recurrence of the tumor in the cervix uteri was diagnosed. As the patient showed no evidence of metastases, a radical hysterectomy was then performed. While the chemotherapy was continued over longer time intervals, the patient lived for a further five months in good health and without any recurrence of the disease. More than one year after treatment was started, the patient died suddenly of uncontrollable cerebral metastases. Considering the unfavourable prognosis and the satisfactory quality of the patient's life after therapy, the course of treatment undertaken appears to have been justifiable. PMID- 2917710 TI - [Is rotation in vacuum extraction possible?]. PMID- 2917711 TI - Coevolution of the major histocompatibility complex and the t-complex in the mouse. I. Generation and maintenance of high complementarity associations. AB - A quantitative model is developed to explore the effects of prezygotic and postzygotic incompatibility on the origin and maintenance of associations between the major histocompatibility complex (MHC) and the t-complex in the mouse. Incompatibility is represented by a reduction in the rate of conception or gestation of offspring derived from sperm bearing MHC antigens in common with the mother. Incompatibility encourages the evolution of associations from a state of complete independence between the two complexes by promoting the invasion of all novel antigens, including those that exhibit associations with the t-complex. Incompatibility can modify the relative numbers of antigens associated with each haplotype by actively promoting the exclusion or invasion of recombinants that bear formerly +-specific or t-specific antigens on the alternative haplotype. The results of the analysis indicate that the state of complete independence between the MHC and the t-complex is not preserved over evolutionary time in the presence of incompatibility. Further, the expression of incompatibility maintains fully associated states that include a single antigen associated with the t-haplotype and up to three to five antigens associated with the +-haplotype within a single population. PMID- 2917712 TI - Coevolution of the major histocompatibility complex and the t-complex in the mouse. II. Modification of response to sharing of histocompatibility antigens. AB - Selective pressures imposed by high complementarity associations between the major histocompatibility complex (MHC) and the t-complex on a locus that modifies the expression of prezygotic and postzygotic incompatibility are investigated through the analysis of a quantitative model. Sharing of MHC antigens between mates or between mother and offspring elicits weak inhibition of conception or gestation. In the presence of high complementarity associations between the MHC and the t-complex, weak incompatibility depresses the mean fitness of the population. Nevertheless, natural selection favors the enhancement of the expression of incompatibility if the number of antigens associated with the + haplotype exceeds the number associated with the t-haplotype by a sufficient margin. Under absolute linkage between the modifier locus and the t-complex, the number associated with the +-haplotype need only be greater than the number associated with the t-haplotype. In the absence of linkage, a twofold difference is sufficient to ensure the initial increase of modifier alleles that intensify the expression of incompatibility. PMID- 2917713 TI - Linkage and the maintenance of heritable variation by mutation-selection balance. AB - The role of linkage in influencing heritable variation maintained through a balance between mutation and stabilizing selection is investigated for two different models. In both cases one trait is considered and the interactions within and between loci are assumed to be additive. Contrary to most earlier investigations of this problem no a priori assumptions on the distribution of genotypic values are imposed. For a deterministic two-locus two-allele model with recombination and mutation, related to the symmetric viability model, a complete nonlinear analysis is performed. It is shown that, depending on the recombination rate, multiple stable equilibria may coexist. The equilibrium genetic and genic variances are calculated. For a polygenic trait in a finite population with a possible continuum of allelic effects a simulation study is performed. In both models the equilibrium genetic and genic variances are roughly equal to the house of-cards prediction or its finite population counterpart as long as the recombination rate is not extremely low. However, negative linkage disequilibrium builds up. If the loci are very closely linked the equilibrium additive genetic variance is slightly lower than the house-of-cards prediction, but the genic variance is much higher. Depending on whether the parameters are in favor of the house-of-cards or the Gaussian approximation, different behavior of the genetic system occurs with respect to linkage. PMID- 2917714 TI - Genes that implement the hermaphrodite mode of dosage compensation in Caenorhabditis elegans. AB - We report a genetic characterization of several essential components of the dosage compensation process in Caenorhabditis elegans. Mutations in the genes dpy 26, dpy-27, dpy-28, and the newly identified gene dpy-29 disrupt dosage compensation, resulting in elevated X-linked gene expression in XX animals and an incompletely penetrant maternal-effect XX-specific lethality. These dpy mutations appear to cause XX animals to express each set of X-linked genes at a level appropriate for XO animals. XO dpy animals are essentially wild type. Both the viability and the level of X-linked gene expression in XX animals carrying mutations in two or more dpy genes are the same as in animals carrying only a single mutation, consistent with the view that these genes act together in a single process (dosage compensation). To define a potential time of action for the gene dpd-28 we performed reciprocal temperature-shift experiments with a heat sensitive allele. The temperature-sensitive period for lethality begins 5 hr after fertilization at the 300-cell stage and extends to about 9 hr, a point well beyond the end of cell proliferation. This temperature-sensitive period suggests that dosage compensation is functioning in XX animals by mid-embryogenesis, when many zygotically transcribed genes are active. While mutations in the dpy genes have no effect on the sexual phenotype of otherwise wild-type XX or XO animals, they do have a slight feminizing effect on animals whose sex-determination process is already genetically perturbed. The opposite directions of the feminizing effects on sex determination and the masculinizing effects on dosage compensation caused by the dpy mutations are inconsistent with the wild-type dpy genes acting to coordinately control both processes. Instead, the feminizing effects are most likely an indirect consequence of disruptions in dosage compensation caused by the dpy mutations. Based on the cumulative evidence, the likely mechanism of dosage compensation in C. elegans involves reducing X-linked gene expression in XX animals to equal that in XO animals via the action of the dpy genes. PMID- 2917715 TI - Ethical care of the elderly: pitfalls and principles. AB - Ethical problems have become intrinsic to geriatric medicine. Physician's familiarity with ethical principles of medical decision-making, such as beneficence, autonomy, and justice, can be helpful. These principles can lead, however, to conflicting conclusions, and the decisions must be personal. An informed approach can help physicians resolve these increasingly commonplace dilemmas. PMID- 2917717 TI - Reimbursement comes to the fore. PMID- 2917716 TI - Conversation with...Ken Dychtwald, PhD: where will the 'age wave' carry physicians?. Interview by Richard L. Peck. PMID- 2917718 TI - Burn accidents and the elderly: what is happening and how to prevent it. AB - Individuals over 60 and children under 2 form the two most burn-prone age groups in the United States. These figures are confirmed in other western cultures. The majority of injuries sustained in these two groups are preventable and relate to inadvertent scalding from hot water at the tap or spilled liquids in the kitchen and ignition of fabrics by faulty heaters or cigarettes. These injuries among the elderly lead to permanent change in health care status in over 40% of such accidents, and their prevention could significantly reduce morbidity associated with aging. Recommendations to promote burn prevention include reducing the temperature of hot water at the tap, introducing self-extinguishing cigarettes, and placing smoke detectors in all residences. PMID- 2917719 TI - Sexual problems in the elderly, I: The use and abuse of medications. A Geriatrics panel discussion. AB - If sexual activity is not off-limits for elderly people, is it at least off limits as a topic of conversation with their physicians? The assumption that it is often prevents informed clinical intervention and leads to needless suffering. Panelists in this first installment in a special two-part discussion defined a broad role for primary care management of sexual dysfunction in the elderly. Drug side effects and appropriate use of estrogens are covered in this installment. PMID- 2917720 TI - Sexual problems in the elderly, II: Men's vs. women's. A Geriatrics panel discussion. AB - As men and women age, each sex finds a particular type of sexual dysfunction becoming more prevalent. For each dysfunction, furthermore, the primary care physician has a management role. The major dysfunctions and what to do about them is reviewed by an expert panel. The second installment in a two-part discussion. PMID- 2917721 TI - Cardiac valve disorders: growing significance in the elderly. AB - Accompanying the aging of the population has been a change in the presentation and the manifestations of valvular heart disease. Calcific aortic stenosis is now the most frequent reason for valvular heart surgery and differs greatly from the stenosis produced by rheumatic fever or a congenital bicuspid valve. Mitral insufficiency is found with increasing frequency and is often due to a calcified mitral valve annulus. Mitral valve prolapse, once thought to be a disease found in younger patients, is being diagnosed more and more in the elderly and is a significant cause of mitral regurgitation. It is important for the physician caring for the older patient to be aware of the differing presentations, manifestations, and implications of valvular diseases in the elderly. PMID- 2917722 TI - [Modern gastritis therapy. New pathogenetic concepts. Significance of Campylobacter pylori. Use of bismuth compounds. Report of the 16th meeting of the Bayern Society of Gastroenterology. Bad Durkheim, 21-22 October 1988]. PMID- 2917723 TI - [The threatened heart: prevention and therapy. Report of the seminar: "Coronary circulation disorders: a 20th century epidemic?" 18 November 1988, Dusseldorf]. PMID- 2917724 TI - [Colloid cysts of the 3d ventricle: problems of early intravital diagnosis]. AB - Basing on two own cases with acute signs of increased obstructive intracranial pressure the problem of early diagnosis of colloid cysts of the third ventricle is discussed with special reference to case reports in the literature. In the absence of typical clinical signs and symptoms, there are acute and chronic constellations of signs and symptoms that point to a suspicion of an obstruction of liquor flow by a colloid cyst. It is explained which importance CT and MR assume in the diagnosis of these benign tumours that present a very varied neurological pattern. Special reference is made to the presentation of neuroradiological differential diagnoses and the application of specific examination methods, such as tomography in very thin layers and allowing some time to elapse after contrast medium administration has been effected. PMID- 2917725 TI - [Isolated abducens paralysis--a retrospective study of 165 patients]. AB - In this retrospective study the case reports of 165 patients suffering from an abducens nerve palsy as the main presenting symptom were evaluated. The sixth nerve palsy was more frequent on the left (52%) than on the right hand side (38%), in 10% there was bilateral involvement. In 49 cases a vascular origin was suspected (29.7%), with diabetes mellitus as the most important risk factor (n = 35). Abducens palsies in inflammatory diseases (n = 32, 19.4%) were seen most often in multiple sclerosis (n = 11), viral meningoencephalitis (n = 5) and accompanying systemic viral infections (n = 5). Postvaccinal paresis was seldom (n = 1). Tumours (n = 18, 10.9%) causing sixth nerve paresis were metastases to the brain (n = 7), meningiomas (n = 3) and glioblastomas (n = 2). Nasopharyngeal carcinomas lead in 4 cases to an involvement of the abducens. Aneurysms causing sixth nerve palsy (n = 7, 4.2%) most frequent being located at the intracavernous region of the internal carotid artery (n = 4). In traumatic abducens paresis (n = 5, 3.1%) pathological findings of neuroradiological examinations are rare. In 48 patients (29.1%) diagnosis remained unclear, especially in young adults between the 20th and 40th year of age. Prognosis of abducens paresis is good in lesions of vascular and unknown origin; in these cases non-steroidal antiphlogistics are of benefit. PMID- 2917726 TI - Hemizona assay using salt-stored human oocytes: evaluation of zona pellucida capacity for binding human spermatozoa. AB - Human oocytes were stored (25 degrees C) in 1.5 M MgCl2 for 6-30 days, then utilized in the new hemizona assay (HZA) for tight binding of human spermatozoa [Burkman et al.: Fertil Steril 49:688-697, 1988]. We have compared 1) the ability of matching salt-treated hemizonae or dimethylsulfoxide (DMSO)-treated hemizonae to distinguish between sperm from semen having normal versus subnormal characteristics and, 2) the kinetics of fertile sperm binding to salt-treated or DMSO-treated hemizonae. After sperm preparation one salt-treated hemizona was incubated with normal spermatozoa and the matching hemizona was placed with sperm from the subnormal group. As a control, DMSO-treated hemizonae were incubated in additional sperm droplets. After 4 hours, the number of sperm tightly bound to each hemizona was counted. Within the normal semen group, there was equivalent binding to salt- or DMSO-treated hemizonae (54.0 +/- 12 and 49 +/- 14, respectively, mean +/- SEM). Similarly, tight binding of sperm from the subnormal group was not affected by the zona storage method (21 +/- 8 and 17 +/- 5, respectively). For either storage approach, binding of subnormal sperm was significantly less (P less than 0.01) compared with the number of normal sperm attached to the matching hemizona. For the kinetics study, the hemizona binding of proven fertile spermatozoa was followed throughout 8.5 hours. The shape of the binding curve was the same for zonae stored by either method and was consistent with our published kinetics data. Salt storage offers a simple and inexpensive means for accumulating and transporting human zonae pellucida; the resulting hemizonae function effectively in the HZA for estimating sperm binding potential. PMID- 2917727 TI - Fertilization by sperm injection in the rabbit. AB - Whole rabbit spermatozoa and isolated sperm nuclei were microinjected directly into the ooplasm of hamster and rabbit ova. These injected sperm decondensed and formed male pronuclei during subsequent in-vitro culture. Injection of whole spermatozoa and sperm nuclei prepared by a protocol known to allow in-vitro capacitation of ejaculated spermatozoa yielded a significantly higher (P less than 0.01) number of activated rabbit ova containing male pronuclei than did injection of uncapacitated epididymal sperm nuclei or ejaculated sperm nuclei. Rabbit ova fertilized by sperm injection were capable of undergoing normal appearing cleavage division during 22 h of culture. PMID- 2917728 TI - Analysis of the chromosome complement in outbred mouse sperm fertilizing in vitro. AB - The chromosome complements in a population of mouse sperm from random-bred ICR donors were analyzed at first-cleavage metaphase after in vitro fertilization (IVF) of oocytes from females of the same strain. The sperm were aged as donations occurred within an average of 31 days, either since last mating or at arrival at the animal facility in the case of virgin males. Of a total of 598 sperm complements studied from 22 sexually mature males aged 10-26 weeks old, there was one diploid complement (0.17%). The frequencies of hyperhaploidy and structural aberrations that were studied in 338 complements were 4.4% and 3.6%, respectively, giving an overall frequency of 8.0%. The hyperhaploid complements consisted of n + 1, n + 2, n + 3, and n + 7 counts, while the structural abnormalities were of the chromosome type and included large and small fragments and a possible translocation. This is the highest frequency of sperm chromosome abnormalities reported for mouse sperm obtained from males under physiological conditions and fertilized in vitro or in vivo. Sperm aging, strain, and/or technique differences are among the factors that may be responsible for this high frequency. Since the 8.0% frequency of hyperhaploidy and structural abnormalities is similar to the frequency reported for human sperm after IVF, the outbred murine in vitro fertilization system may be a useful model to study the origin of human sperm chromosome abnormalities. PMID- 2917729 TI - Incidence of chromosomal anomalies in early bovine embryos derived from in vitro fertilization. AB - The incidence of chromosomal anomalies in early bovine embryos derived from follicular oocytes fertilized in vitro using sperm separated by Percoll density gradient centrifugation was investigated. Overall, chromosomal anomalies were observed in 13.7% (138/1005) of embryos. There were 14 haploids (1.4%), 2 hypodiploids (0.2%), 6 hyperdiploids (0.6%), 101 triploids (10.0%), 12 tetraploids (1.2%), 2 diploid/triploid mosaics (0.2%), and 1 diploid/tetraploid mosaic (0.1%). The frequency of triploidy was caused mainly by polyspermy. There was a significant difference in the frequency of embryos with abnormal chromosomes between the two bulls used (P less than 0.005), but Percoll centrifugation did not affect the observed incidence of anomalies. The frequency of chromosomal anomalies in embryos at each stage increased with delay or arrest of development. These results suggest that the incidence of chromosomal anomalies depended on the conditions of in vitro fertilization and the arrest of development. PMID- 2917730 TI - Segregation products of male mice doubly heterozygous for the RB(6.16) and RB (16.17) translocations: influence of sperm karyotype on fertilizing competence under varying mating frequencies. AB - The meiotic segregants of male mice heterozygous for Rb(6.16)24Lub and Rb(16.17)7Bnr were viewed, for the first time, at first cleavage metaphase. Chromosomes were analyzed after G-banding, C-banding, and karyotyping. To study sperm aging effects, chromosomes of 202 one-cell zygotes derived from males mating at intervals of approximately 3, 14, and 21 days were examined. At least 89.6% of sperm-derived complements were products of 2:2 segregation; at most, a possible 6.4% were 3:1 segregants. The six expected types of 2:2 segregants, both balanced and unbalanced, were equifrequent in the total zygote population derived from sperm of all ages. When the data were analyzed according to mating frequency, the 3-day sperm population considered most likely to be fresh showed a deficiency of the segregant nullisomic for chromosome 6 and disomic for chromosome 17, when compared with the reciprocal segregant (P less than 0.025) as well as to all other 2:2 segregants (P less than 0.05). However, these sperm fertilized in greater numbers (P less than 0.01) than their reciprocal segregant (disomic for 6 and nullisomic for 17) in the 14-day sperm population. While sperm with chromosomal abnormalities are capable of fertilization, the competence of segregants nullisomic for 6 and disomic for 17 apparently depends on the prior storage period in the male. Further, the results suggest that the effect of aneuploidy on sperm function is dependent on the specific chromosome(s) involved. PMID- 2917731 TI - The place of work in psychiatric rehabilitation. PMID- 2917732 TI - The legacy of model programs. PMID- 2917733 TI - ECT for an elderly man with psychotic depression and concurrent dementia. PMID- 2917734 TI - The expansion of psychiatric participation in social control. PMID- 2917735 TI - Assessing the victimized psychiatric patient. AB - Psychiatric patients who have experienced violence or victimization usually do not report these traumatic events to clinicians spontaneously, although they may be relevant to the patients' current problems. Therefore, inquiry about such experiences should be part of the clinical assessment of patients who are refugees, crime victims, or military veterans or patients whose histories suggest traumatic events. The authors present a series of questions designed to facilitate discussion of traumatic events and to elicit clinical information that is relevant from both somatic and psychosocial perspectives. PMID- 2917737 TI - The development and practice of pastoral counseling. AB - The practice of pastoral counselors is not well understood by secular mental health professionals, although evidence suggests that advantages can be gained by increasing the interaction between the two groups. Trends in the historical development of pastoral counseling are summarized, and a typology that distinguishes three major thrusts among its practitioners--religious counseling, pastoral mental health work, and pastoral psychotherapy--is offered. A clergy malpractice case that raises issues of joint concern to secular and religious therapists is discussed. PMID- 2917736 TI - Do dangerousness-oriented commitment laws restrict hospitalization of patients who need treatment? A test. AB - A study at a large urban psychiatric hospital in Pennsylvania evaluated whether the state's dangerousness-oriented commitment criteria restricted hospitalization of patients whom emergency room clinicians considered highly in need of treatment but not dangerous. A total of 390 patients were studied. Eleven patients judged to be highly in need of treatment did not meet any of the commitment criteria, but they were largely compliant with the idea of being treated. An additional 17 patients considered highly in need of treatment met criteria for commitment based on inability to care for self, but most were hospitalized voluntarily. Only one patient who met none of the commitment criteria resisted recommended hospital care, and she was eventually committed involuntarily based on inability to care for self. The data suggest that dangerousness-oriented commitment criteria are flexible enough to provide for treatment of patients in serious need. PMID- 2917738 TI - Changes in VA diagnosis of schizophrenic and affective disorders after DSM-III. AB - DSM-III tightened the criteria for diagnosis of schizophrenia by excluding patients who exhibit a full affective syndrome before the onset of psychotic symptoms; such patients are to receive a diagnosis of affective disorder. The impact of this change on psychiatric diagnostic practices in Veterans Administration facilities before and after publication of DSM-III was assessed. Diagnoses of schizophrenia increased about half as much as would be expected based on the overall increase in psychiatric diagnoses, while diagnoses of affective disorders rose about two and a half times as much as would be expected. Patients whose diagnoses were changed from schizophrenic to affective disorders after publication of DSM-III had significantly fewer hospitalizations in both time periods than patients who retained diagnoses of schizophrenia. However, greater diagnostic inconsistency was found after implementation of DSM-III. PMID- 2917739 TI - Impact of therapeutic management on use of seclusion and restraint with disruptive adolescent inpatients. AB - Use of seclusion and restraint on three inpatient adolescent psychiatric units was examined during two five-month periods before and after implementation of a "therapeutic management" protocol. Under the protocol, staff classified disruptive behaviors into four stages and provided verbal and behavioral interventions to control behavior at each stage. Patients who required seclusion and restraint had significant latitude to determine the timing of their release from the interventions and met with staff one hour and 24 hours after their release to explore alternatives to aggression. The number of episodes of seclusion and restraint fell by 64 percent after the protocol was adopted, and the number of patients who required those interventions dropped by 39 percent. The mean duration of episodes of seclusion and restraint was reduced by 59 percent. Therapeutic management provides a corrective experience by addressing the developmental needs, deficient cognitive skills, and poor internalized controls of disruptive adolescents. PMID- 2917741 TI - Missed diagnosis of substance abuse in psychiatric patients. PMID- 2917740 TI - Urban psychiatric commitments: disability and dangerous behavior of black and white recent admissions. AB - Nationally black patients are overrepresented in public psychiatric institutions and are more likely than white patients to be committed involuntarily. This study of patients from 12 treatment units in the Chicago area, where these patterns were also true, compared the functioning of 227 acute admissions grouped by race (white or black) and admission status (voluntary or involuntary). Patients were assessed by highly trained independent observers using objective measures of dangerous behavior and disability levels, the relevant classes of functioning based on common principles underlying commitment statutes. No evidence was found that racial bias and discrimination in commitment and retention decisions would account for the overrepresentation of blacks among involuntary commitments to public institutions. Rather, the same factors that account for the overrepresentation of blacks compared with whites among all admissions may also explain their overrepresentation among the involuntarily confined. Changes in treatment programming and assessment practices are suggested. PMID- 2917742 TI - AMA discharges: prediction and treatment outcome. PMID- 2917743 TI - Davanloo's technique. PMID- 2917744 TI - Accusations of child abuse. PMID- 2917745 TI - Labeling patients. PMID- 2917746 TI - CA Blue Cross posts big gain in third-quarter '88. PMID- 2917747 TI - HAS Monitrend II: faster data, more detail. PMID- 2917748 TI - Reducing cesareans--a $1 million trade-off. PMID- 2917749 TI - Rehabilitation growth: is its heyday over? PMID- 2917750 TI - Rehabilitation growth fuels PT shortages. PMID- 2917751 TI - Researchers reconsider plants as drug sources. PMID- 2917752 TI - Image problems expand CEO role. PMID- 2917753 TI - Public image intact after antitrust trial ends. PMID- 2917754 TI - Marketers' survey: advertising decline continues. PMID- 2917755 TI - Hospital CEOs make commitment to child care. PMID- 2917756 TI - Salaries reflect value of physician managers. PMID- 2917757 TI - Meet CEO Inez Lemke: "This is where my heart is". Interview by Alden Solovy. PMID- 2917759 TI - Hospital closings reach 81 in 1988: AHA report. PMID- 2917758 TI - Labs in microcosm: what's happening in Denver. PMID- 2917760 TI - Executive resumes: the ultimate calling card. PMID- 2917761 TI - Market research: 'Let the buyer beware'. PMID- 2917762 TI - Realistic conductivity geometry model of the human head for interpretation of neuromagnetic data. AB - In this paper, the computational and practical aspects of a realistically-shaped multilayer model for the conductivity geometry of the human head are discussed. A novel way to handle the numerical difficulties caused by the presence of the poorly conducting skull is presented. Using our method, both the potential on the surface of the head and the magnetic field outside the head can be computed accurately. The procedure was tested with the multilayer sphere model, for which analytical expressions are available. The method is then applied to a realistically-shaped head model, and it is numerically shown that for the computation of B, produced by cerebral current sources, it is sufficient to consider a brain-shaped homogeneous conductor only since the secondary currents on the outer interfaces give only a negligible contribution to the magnetic field outside the head. Comparisons with the sphere model are also included to pinpoint areas where the homogeneous conductor model provides essential improvements in the calculation of the magnetic field outside the head. PMID- 2917763 TI - Optimal stroke volume in left-ventricular ejection. AB - Previous papers related to the recent concept of matching between the ventricle and arterial load have only dealt with the optimization of arterial load. Thus, stroke volumes predicted by the suggested models for an optimal arterial load have only been analyzed. In this paper, optimal value of stroke volume ejected against a given arterial load was studied, i.e., left-ventricular function was described by an optimization model. In the model, end-diastolic volume (Ved), the linear end-systolic pressure-volume relation, heart rate, and ejection time are given and arterial load is described by the three-element wind-kessel model. The cost function of the model takes into account two optimality criteria for ventricular function: energy economy and efficient response to an increase in Ved. The observed stroke volumes of isolated canine hearts (data from the literature) could be predicted quite accurately by the model. It was concluded that the left-ventricular response to a change in arterial load and Ved can be explained by an optimization model when contractility and heart rate are kept constant. The results also strongly suggest that energy economy and efficiency are essential features of left-ventricular function. PMID- 2917764 TI - A mathematical model of cerebral blood flow chemical regulation--Part I: Diffusion processes. AB - This paper proposes a mathematical model which describes the production and diffusion of vasoactive chemical factors involved in oxygen-dependent cerebral blood flow (CBF) regulation in the rat. Partial differential equations describing the relations between input and output variables have been replaced with simpler ordinary differential equations by using mathematical approximations of the hyperbolic functions in the Laplace transform domain. This model is composed of two submodels. In the first, oxygen transport from capillary blood to cerebral tissue is analyzed to link changes in mean tissue oxygen pressure with CBF and arterial oxygen concentration changes. The second submodel presents equations describing the production of vasoactive metabolites by cerebral parenchyma, due to a lack of oxygen, and their diffusion towards pial perivascular space. These equations have been used to simulate the time dynamics of mean tissue PO2, perivascular adenosine concentration, and perivascular pH to changes in CBF. The present simulation points out that the time delay introduced by diffusion processes is negligible if compared with the other time constants of the system under study. In a subsequent work the same equations will be included in a model of the cerebral vascular bed to clarify the metabolite role in CBF regulation. PMID- 2917765 TI - A mathematical model of cerebral blood flow chemical regulation--Part II: Reactivity of cerebral vascular bed. AB - In the present paper an original mathematical model of the chemical oxygen dependent cerebral blood flow (CBF) regulation in the rat is proposed. Taking into account recent experimental works, the model assumes that oxygen acts on cerebral vessels through an indirect mechanism, mediated by the release of two metabolic substances (adenosine and H+) from tissue, and that any change in perivascular concentration of these substances affects the diameter of both the medium and small pial arteries as well as of intracerebral arterioles. The model is composed of several submodels, each closely related to a different physiological event. mathematical equations, which describe the reaction of the vasoactive portion of the cerebral vascular bed, are reported in detail and justified. The model permits the simulation of the role played by chemical factors in the control of CBF under many different physiological and pathological conditions in an attempt to clarify their relevance. Several events associated with an alteration in oxygen supply to tissue (auto-regulation to changes in arterial and venous pressure, reactive hyperemia following on cerebral ischemia, arterial hypoxia) have been simulated with the model. The results suggest that chemical factors, adenosine and H+, play a significant but not exclusive role in the regulation of the cerebral vascular bed. The action of other mechanisms (which are probably neurogenic) must be hypothesized to explain completely the CBF changes occurring in vivo. PMID- 2917766 TI - The use of adaptive algorithms for obtaining optimal electrical shimming in magnetic resonance imaging (MRI). AB - A method of determining the dc coil current values to electrically shim the static magnetic fields used in magnetic resonance imaging (MRI) using modified steepest descent adaptive algorithm is described. Using a 32 cm diameter by a 40 cm long water phantom as the test volume, the algorithm achieved field homogeneities of 0.2 parts per million (ppm) peak-to-peak within a 20 cm diameter spherical imaging volume, and 1.3 ppm peak-to-peak within the entire phantom. The algorithm achieved an inhomogeneity variance of 0.18 ppm2. The shim system was successfully modeled as a sum of adaptive linear combiners. The model contains 13 parameters that can be varied, 12 shim coil currents, and the receiver mixer frequency. The model was then used to predict key adaptive algorithm parameters. Experimental verification of these parameters lends support to the accuracy of the model. PMID- 2917767 TI - High resolution NMR spectroscopy using a recursive algorithm. AB - When the DFT (discrete Fourier transform) is used as a method for obtaining NMR (nuclear magnetic resonance) spectrum, resolution of the obtained NMR spectrum depends clearly on spin-spin relaxation times of the nucleus and the sampled number of NMR signal. That is, the NMR spectrum is affected by decay of NMR signal due to the relaxation times and errors associated with discrete approximation of NMR spectrum. As a results, its resolution is degraded and the spectrum disagrees with the density distribution of the nucleus. In the present paper, we propose a new NMR spectrum estimation method for reducing their effects, demonstrating a high resolution NMR spectrum which is closer to the density distribution than that of the DFT. The proposed method is derived from applying the Kalman filter or the recursive least-square method to a NMR signal model based on Bloch equation. Under various conditions, the proposed method is compared with the DFT using a proton 1H NMR signal observed from mayonnaise in a 2 [T] static magnetic field. The results show that if spin-spin relaxation times are known previously, the proposed method can provide a higher resolution NMR spectrum than the DFT. In addition, it is shown that the method can reduce the discrete approximation errors of NMR spectrum. Finally, we demonstrate that if frequency components of sources of NMR signal are present in a limited range in frequency domain of interest, the method can magnify NMR spectrum with a sampling time and interval fixed. PMID- 2917768 TI - A tracking FFT processor for pulsed Doppler analysis beyond the Nyquist limit. AB - A tracking procedure for processing ultrasound pulsed Doppler signals with instantaneous frequencies beyond the Nyquist limit is discussed. It is based on the observation that the frequency translation required to properly reconstruct an aliased spectrum can be achieved by means of a simple reordering of data provided by a digital fast Fourier transform (FFT) unit. The amount of reordering is automatically derived by the computed value of a spectral parameter, e.g., the mean frequency. The procedure has been tested by introducing some modifications at the output of an FFT unit included in a conventional pulsed Doppler system. As a result, the dynamic evolution of the full Doppler spectrum and related mean frequency can be followed in real time over an extended range. In vitro and in vivo experiments, as well as quantitative measurements carried on with test signals are presented. PMID- 2917769 TI - Design optimization of interstitial antennas. AB - To improve the performance of interstitial antennas for microwave hyperthermia, parameters such as the uniformity of the heating pattern, the depth of penetration, and the impedance matching properties must be optimized. We examined analytically and experimentally the radiation characteristics of multisection insulated antennas in conductive tissue. The effects of varying the diameters and lengths of the center conductors in the various sections of the antenna and the diameter and type of the insulation on the electromagnetic power deposition pattern and input impedance characteristics were examined. A new approximate numerical model which calculates the current distribution and the radiation characteristics of multisection insulated antennas was developed. The numerical predictions were verified in a qualitative way experimentally by mapping the various near- and far-field components of these antennas. Based on the obtained results, design tradeoffs are identified and quantified, and guidelines for optimum designs are specified. In particular, it is shown that an insulation-to center-conductor diameter ratio between 1.5 to 2.0 is optimum for a uniform Teflon insulation, and that a multisection arrangement with the thinnest insulation near the antenna tip has superior performance compared with the uniform insulation or other multisection designs. PMID- 2917770 TI - Procedure for quantitative comparison of ground reaction data. AB - Measurement of ground reaction forces has been largely adopted for evaluation of gait disorders even if the discussion of obtained results and their comparison with those from normal locomotion are generally related to a purely visual interpretation of the pattern morphology or, at least, to the assessment of a limited number of parameters such as maximal amplitude of force, number of maxima in the envelope, presence of one minimum or more, etc. This paper describes an analytical method for a quantitative and detailed comparison of different ground reaction force patterns. It is based on a suitable processing of the 3-D components of the ground reaction force and is essentially composed of three main frames: verification of the regular recurrence of measurement conditions, normalization, and data comparison. The first frame is to check that the acquired data are not affected by inertial predominance in the direction of progression. Normalization involves the amplitude of force, the application point displacements and the stance-phase duration. Data comparison utilizes a dedicated implementation of an appropriate statistical approach to estimate significant differences between two suitable and typical ground reaction force patterns. In order to show practical examples of the whole analytical procedure, two cases are also presented in detail. PMID- 2917772 TI - Impulsive noise suppression and background normalization of electrocardiogram signals using morphological operators. AB - A new approach to impulsive noise suppression and background normalization of digitized electrocardiogram signals is presented using mathematical morphological operators that incorporate the shape information of a signal. A brief introduction to these nonlinear signal processing operators, as well as a detailed description of the new algorithm, is presented. Empirical results show that the new algorithm has good performance in impulsive noise suppression and background normalization. PMID- 2917771 TI - Four digital algorithms for activation detection from unipolar epicardial electrograms. AB - The reproducibility of activation detection by each of four algorithms used to calculate maximum derivatives was tested on two sequential paced beats of right ventricular unipolar epicardial electrograms which represented either local activation of the right ventricle alone or synchronous activation of both ventricles. The methods were evaluated by comparing the shape of the two beats aligned on their selected activation times, i.e., the time at which the maximum negative deflection occurred, the differences in activation intervals for the two beats, and the effect on the activation time of superimposing distant events on local activation. The 17-point second-order data fit algorithm performed slightly better than the first-order difference, three-point Lagrange derivative, and five point second-order data fit algorithms except that activation time selection by the 17-point technique was slightly, but significantly, delayed by the superposition of distant potentials. The 17-point second-order data fit technique is therefore recommended for use in detecting activation unless computation time is a major consideration. In that case, the five-point second-order data fit technique, which uses only four data values for each computation, can be used with only slight decreases in accuracy. PMID- 2917773 TI - Assessment of autonomic regulation of heart rate variability by the method of complex demodulation. AB - Complex demodulation was used to examine the effect of both divisions of the autonomic nervous system (sympathetic and parasympathetic) on heart rate. Data were analyzed from dogs during classical conditioning procedures which caused different changes in the autonomic regulation of heart rate. Two significant peaks in the heart rate variability spectrum were examined by this technique. The amplitude of the peak at the respiration frequency showed parasympathetic changes, while the amplitude of the low frequency peak (0-0.124 Hz) showed both sympathetic and parasympathetic effects. Complex demodulation results at these frequencies clearly showed the activities of both branches of the autonomic nervous system in regulating heart rate. During the CS+ period, when trained dogs were presented with a tone predicting a subsequent shock, the observed tachycardia was due to decreased parasympathetic activity and a transient increase in sympathetic activity. During the CS- period where a different tone predicts no shock, parasympathetic and sympathetic activities were unchanged from the baseline condition. The use of complex demodulation enables us to examine autonomic contributions to heart rate regulation in conditioning and a variety of other physiological and environmental conditions where autonomic input can be expected to change rapidly. PMID- 2917774 TI - The design and use of a microcomputerized real-time muscle fatigue monitor based on the medial frequency shift in the electromyographic signal. AB - We have designed a real-time microcomputerized muscle fatigue monitor based on the median frequency shift of the electromyographic signal, computed via the fast Fourier transform. For the ten subjects performing an isotonic and isometric trunk extension task on two separate days, preliminary results suggest a repeatable linear decrease in median frequency as a function of time. PMID- 2917775 TI - Vector analysis of three-dimensional evoked potentials: eccentric dipoles. AB - The quantitative description of three-dimensional cerebral evoked potentials is extended to include eccentric dipolar sources. Eccentricity-related distortions in dipole orientation and magnitude are assessed. The use of nonstandard montages, the prediction of topographic surface maps, dynamic analysis, and theoretical mechanisms of planar segment formation are discussed. PMID- 2917776 TI - A practical electrode-array myoprocessor for surface electromyography. AB - A new myoprocessor is described which produces a relatively smooth and accurate measure of a muscle's electrical activity during both slow and rapid movements. This is achieved partly by spatial averaging of weakly correlated EMG signals from electrodes distributed over the surface of the muscle. PMID- 2917777 TI - Serum antibody responses to the N-acetylneuraminyllactose-binding hemagglutinin of Campylobacter pylori. AB - We recently reported that Campylobacter pylori possesses a surface-associated fibrillar hemagglutinin which has an affinity for N-acetylneuraminyllactose; this hemagglutinin may function as a colonization factor for attachment to the gastric epithelium. In the present study we examined serum samples obtained from 65 C. pylori-infected individuals with gastric ulcers, duodenal ulcers, or both and from 121 asymptomatic volunteers, including 62 who were infected with C. pylori, for immunoglobulin G (IgG) specific for the C. pylori neuramin-lactose-binding hemagglutinin (NLBH). The NLBH purified from a single isolate was used as the antigen in an enzyme-linked immunosorbent assay. A positive result was obtained with serum from 81.5% (53 of 65) of the individuals with ulcers, 67.7% (42 of 62) of the C. pylori-infected volunteers, and 1.7% (1 of 59) of the C. pylori negative volunteers. This result confirms that NLBH is produced in vivo. There are several possible explanations for the fact that only 75% of 127 C. pylori infected individuals were positive for anti-NLBH IgG in serum. We favor the hypothesis that there are probably several antigenically distinct C. pylori NLBHs, i.e., NLBHs which would stimulate antibody that was undetectable by the antigen used in the enzyme-linked immunosorbent assay described here. PMID- 2917778 TI - Identification of stage-specific antigens of Toxoplasma gondii. AB - An immunologic evaluation of the surface antigens of the three major life-cycle stages of Toxoplasma gondii was performed. Mouse antisera were raised against these stages, which included the oocyst-sporozoite (feline-excreted stage), bradyzoite (chronic tissue cyst stage), and tachyzoite (invasive stage). The antisera were used in an enzyme-linked immunosorbent assay and Western blot (immunoblot) analysis to demonstrate the presence of stage-specific antigens. These antigens were of various molecular weights and were specific to each stage investigated. Cross-reaction studies showed that the mouse antisera recognized commonly shared antigens to at least two of the three stages. A panel of monoclonal antibodies identified specific immune epitopes unique to each of the stages investigated. These studies further support the hypothesis that stage specific antigens are present in T. gondii. PMID- 2917779 TI - Immunohistochemical and electron microscopic study of interaction of Yersinia enterocolitica serotype O8 with intestinal mucosa during experimental enteritis. AB - The experimental infection of mice with Yersinia enterocolitica serotype O8 was investigated in a quantitative and histological study. The course of bacterial penetration and spreading was precisely determined by immunohistochemical staining. After oral administration, the bacteria passed the epithelial barrier of the ileum and spread into the lamina propria. By preference they entered Peyer's patches, which were about 1,000 times more heavily colonized than the surrounding epithelium of a comparable surface area. The bacteria proliferated in the follicles, from which they spread into the lamina propria of the villi. At either site most of the bacteria multiplied extracellularly, with only a small percentage observed to be present within the phagocytes. The bacteria did not appear to be able to pass the intact basement membrane; hence, the integrity of the basement membrane is likely to play a role in determining the route of entry and limit of spread of Y. enterocolitica infection. PMID- 2917780 TI - Mannan as an antigen in cell-mediated immunity (CMI) assays and as a modulator of mannan-specific CMI. AB - Mannan (MAN) extracted from Candida albicans 20A was investigated for its potential as an antigen in the detection of cell-mediated immunity (CMI) in vivo and in vitro and for its ability to modulate CMI when administered intravenously (i.v.). CBA/J mice were either immunized as adults by the cutaneous inoculation of 10(6) viable blastoconidia or colonized as infants (primed) and then boosted cutaneously as adults. When immunized animals were footpad tested with MAN, highly significant delayed-type hypersensitivity (DH) responses were detected. The DH responses to MAN were of a greater magnitude than those noted with the same quantity of cell wall glycoprotein (GP), an ethylenediamine extract of the cell wall which contains both glucan and MAN. In contrast, GP was a better antigen for the detection of CMI responses in an in vitro lymphoproliferative assay with either spleen or lymph node cell suspensions. Mice treated with MAN i.v. prior to the initiation of immunization or between priming and secondary inoculations developed significantly suppressed DH reactions when tested with either MAN or GP. The lowest effective dose of MAN was 250 micrograms, maximum suppression occurred with 500 micrograms, and either dose given 1 week prior to immunization was suppressive. The suppression by MAN was specific for MAN or the MAN-containing GP. Responses to another unrelated candidal antigen, a membrane extract designated BEX, were relatively unaffected. MAN, therefore, was an effective antigen for the detection of CMI in vivo, and its administration i.v. created what appeared to be a MAN-specific suppression since it could be detected with both MAN and a MAN-containing extract from the cell wall. Caution must be exercised in the interpretation of these data, however, since the protein component of each of these extracts has not been characterized with respect to its potential role in the phenomena observed. PMID- 2917781 TI - Major histocompatibility complex control of immunity elicited by genetically engineered Eimeria tenella (Apicomplexa) antigen in chickens. AB - The immunogenicity of a recombinant Eimeria tenella coccidial antigen was studied in 6(1).B congenic chickens derived from B2B2 and B5B5 parents segregating for haplotypes B2 and B5. Five-week-old chickens were immunized with 2.4 micrograms of recombinant protein (designated 5401) in Freund complete adjuvant and challenged with 75,000 oocysts at 28 days postimmunization (DPI) to determine the degree of elicited protective immunity. Serum samples were collected weekly for 5 weeks postimmunization for analysis by enzyme-linked immunosorbent assay, immunofluorescence assay, and Western blotting. Lesion scores following oocyst challenge were significantly reduced in B5B5 chickens compared with those in B2B2 chickens. Immunization induced a sporozoite-specific immunoglobulin G (IgG) titer in serum detected by the enzyme-linked immunosorbent assay that peaked at 28 DPI, the day of challenge, in B5B5 chickens and at 42 DPI in B2B2 chickens. After challenge, this titer declined for each genotype. Anti-sporozoite IgG detected by the immunofluorescence assay attained a peak titer at 21 DPI in B2B2 chickens and 28 DPI in B5B5 chickens. Serum from immunized B5B5 chickens reacted strongly in Western blots with several high-molecular-weight (greater than 100,000), soluble proteins prepared from sporozoites. Serum from B2B2 chickens reacted with similar proteins as well as with a 51- to 53-kilodalton protein that was not labeled by serum from B5B5 chickens. These results demonstrate further the role of host genetics on anticoccidial immunity and suggest that a peak anti-sporozoite IgG titer in B5B5 chickens on the day of challenge may signal a state of immunocompetence to that challenge. PMID- 2917782 TI - Role of cell-mediated immunity in the resolution of secondary chlamydial genital infection in guinea pigs infected with the agent of guinea pig inclusion conjunctivitis. AB - Guinea pigs which have recovered from a genital infection with the agent of guinea pig inclusion conjunctivitis demonstrate strong immunity to reinfection for a short period of time but then become susceptible to reinfection. The secondary infection is markedly shortened in duration and decreased in intensity. Previous studies have indicated an important role for humoral immunity in resistance to and in recovery from reinfection. However, the contribution of cell mediated immunity to immunity toward or recovery from a secondary infection is not clear. Guinea pigs were infected in the genital tract with guinea pig inclusion conjunctivitis and were challenged at either 30 or 75 days after the primary infection. Prior to challenge, one group of animals were injected with rabbit anti-guinea pig thymocyte serum (ATS) while control groups received either normal rabbit serum or no treatment. Treatment was continued daily for the course of the experiment. On day 30, ATS-treated guinea pigs had a slightly higher rate of reinfection, and generally the infection persisted longer than in controls. On day 75, all animals became reinfected upon challenge, but control animals resolved their infections in 3 to 9 days. In contrast, most ATS-treated animals remained infected throughout the course of the experiment. Although the animals became reinfected, the levels of chlamydiae were much lower than those observed during the primary infection. ATS treatment abrogated T-cell responses, but serum and secretory antibody responses remained normal. Histopathological examination revealed some decrease in mononuclear infiltration of endocervical and uterine tissues in ATS-treated animals. These data indicate that previously infected guinea pigs require both cell-mediated immunity and humoral immunity for resolution of a challenge infection. PMID- 2917783 TI - Pasteurella haemolytica antigens associated with resistance to pneumonic pasteurellosis. AB - Antigens associated with whole Pasteurella haemolytica biotype A serotype 1, a capsular carbohydrate-protein extract of the organism, and P. haemolytica leukotoxin were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Antigens of the electrophoresed preparations were detected by Western blotting (immunoblotting) with sera from cattle which were either nonvaccinated or vaccinated with live or killed P. haemolytica vaccines and had variable degrees of resistance to experimental pneumonic pasteurellosis. Distinct, easily recognizable antigens of these preparations were identified, and the antibody responses to these antigens were quantified by densitometry. To determine their importance to disease resistance, we then compared antibody responses with experimental lesion scores. Antibody reactivity to surface antigens which were significantly correlated with resistance and present in two or more of the preparations were detected at 86, 66, 51, 49, 34, 31, and 16 kilodaltons (kDa). Of these, antibody responses to antigens at 86, 49, and 31 kDa appeared most important based on their concentration and significance levels. Antibody reactivity to leukotoxin antigens which were significantly correlated with resistance and common with important surface antigens were detected at 86, 66, and 49 kDa. Antibody responses to unique leukotoxin antigens which were significantly correlated with resistance were present at 92 and 58 kDa. PMID- 2917784 TI - Comparison of the biological responses induced by lipopolysaccharide and endotoxin of Treponema hyodysenteriae and Treponema innocens. AB - The chemical composition and classical biologic activities of lipopolysaccharide (LPS; phenol-water) and endotoxin (butanol-water) preparations from virulent Treponema hyodysenteriae and avirulent Treponema innocens were examined. The LPS and endotoxin preparations from T. hyodysenteriae B204 contained approximately 80.9 and 35.2% hexose, 0.12 and 0.45% thiobarbituric acid-reactive compound, and less than 1 and 11.3% protein, respectively. The LPS and endotoxin preparations of T. innocens B1555a contained approximately 56.3 and 37.8% hexose, 0.45 and 0.4% thiobarbituric acid-reactive compound, and less than 1 and 26% protein, respectively. A silver-stained 7.5 to 15% sodium dodecyl sulfate-polyacrylamide gel showed four bands for the T. hyodysenteriae preparations, while the T. innocens preparations failed to resolve into discrete bands on electrophoresis. We determined by the Limulus amebocyte lysate assay that the treponemal preparations had comparable amounts of endotoxin activity when Escherichia coli LPS was used as a standard. The 50% lethal doses of LPS and endotoxin from T. hyodysenteriae for BALB/cByJ mice were 380 and 80 micrograms, respectively. The treponemal preparations were poor adjuvants, failed to induce a dermal Shwartzman reaction, and were not pyrogenic. The treponemal LPS preparations, unlike the endotoxin preparations, were not mitogenic for murine spleen cells. Differences in virulence between the two treponemal species could not be associated with the biologic activities of the respective LPS or endotoxin moieties, but the endotoxin preparations were consistently more active than the purified LPS preparations. PMID- 2917785 TI - Characterization of a Legionella pneumophila extracellular protease exhibiting hemolytic and cytotoxic activities. AB - A preliminary screening of selected Legionella species for proteolytic and hemolytic phenotypes suggested a correlation between these activities. To investigate the relationship of these phenotypes, a mutant strain of Legionella pneumophila deficient in the expression of a 38-kilodalton (kDa) exoprotease was isolated and characterized. This strain, designated PRT8, was also found to be nonhemolytic when screened on blood agar composed of 5% canine or guinea pig erythrocytes. Strain PRT8 was serologically and biochemically identical to the parental strain with the exception of the expression of the exoprotease. Immunoblot analysis of concentrated culture filtrates from PRT8 probed with polyclonal anti-38-kDa exoprotease serum revealed no cross-reactive peptides. To resolve the role of the exoprotease in the hemolytic phenotype, the exoprotease was purified from the culture supernatant of the parental strain by a combination of ion-exchange and hydrophobic interaction chromatography steps. The hemolytic activity was found to copurify with the proteolytic activity, and analyses by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblot revealed a single protein species exhibiting an apparent molecular mass of 38 kDa. Finally, the purified exoprotease and concentrated culture supernatant from the parental strain, but not from PRT8, exhibited cytotoxicity (minimum cytotoxic activity of 0.17 U of protease activity) in a Chinese hamster ovary cell assay. These data suggest that the exoprotease is responsible for the hemolytic and cytotoxic phenotypes described for this species and therefore may be one of several determinants associated with virulence. PMID- 2917786 TI - Immunoprophylaxis of Chlamydia trachomatis lymphogranuloma venereum pneumonitis in mice by oral immunization. AB - Groups of BALB/c mice were orally immunized with chlamydiae and challenged intranasally to determine whether oral immunization offers protection against pulmonary disease and to characterize the nature and kinetics of the chlamydial antibody response in the lung and other mucosal sites. Protection by oral immunization from chlamydial lung disease was demonstrated by lack of replication of the organism and the lack of chlamydial antigen in lung tissue. The chlamydial immunoglobulin A (IgA) antibody response was present at all body sites, reaching peak levels in the lung as well as in the serum. Classical IgA booster effect kinetics was observed after intranasal challenge, especially in the lung. Specific IgG antibody was detected at all body sites but at lower levels. Furthermore, animals immunized orally had no pneumonic process, as determined by histopathology. These studies also suggest that passively acquired specific serum IgG antibody may not significantly influence the course of mucosal replication of the organism. These observations indicate that oral immunization activating the gut-associated lymphoid tissue system gave total protection against chlamydial lung disease, suggesting migration of immunologically competent cells from the intestine to the lung. PMID- 2917787 TI - Effect of iron restriction on the outer membrane proteins of Actinobacillus (Haemophilus) pleuropneumoniae. AB - The outer membrane protein profile of Actinobacillus (Haemophilus) pleuropneumoniae grown under iron-restricted and iron-replete conditions was studied by polyacrylamide gel electrophoresis and immunoblotting. A virulent serotype 1 isolate synthesized a novel protein with an apparent molecular weight of 105,000 (105K) and increased the synthesis of a 76K protein under iron restricted conditions. Both proteins were synthesized within 15 min of establishment of iron-restricted conditions. Proteins of equivalent molecular weights could also be induced by iron restriction in serotype 2, 3, 4, 5, and 7 isolates of A. pleuropneumoniae. Convalescent-phase sera from serotype 1-infected pigs contained antibodies which recognized both the 105K and 76K proteins from all six serotypes examined, indicating that these proteins were expressed in vivo and were immunologically conserved. Cells expressing the 105K and 76K proteins also displayed an enhanced ability to bind Congo red and hemin, suggesting that one or both of these proteins functioned to acquire complexed iron during in vivo growth. PMID- 2917788 TI - Cariogenicity of a lactate dehydrogenase-deficient mutant of Streptococcus mutans serotype c in gnotobiotic rats. AB - A lactate dehydrogenase-deficient (Ldh-) mutant of a human isolate of Streptococcus mutans serotype c was tested in a gnotobiotic rat caries model. Compared with the wild-type Ldh-positive (Ldh+) strains, it was significantly (alpha less than or equal to 0.005) less cariogenic in experiments with two different sublines of Sprague-Dawley rats. The Ldh- mutant strain 044 colonized the oral cavity of the test animals to the same extent as its parent strain 041, although its initial implantation was slightly but not significantly (P greater than or equal to 0.2) less. Multiple oral or fecal samples plated on 2,3,5 triphenyltetrazolium indicator medium revealed no evidence of back mutation from Ldh- to Ldh+ in vivo. Both Ldh+ strain 041 and Ldh- strain 044 demonstrated bacteriocinlike activity in vitro against a number of human strains of mutans streptococci representing serotype a (S. cricetus) and serotypes c and e (S. mutans). Serotypes b (S. rattus) and f (S. mutans) and strains of S. mitior, S. sanguis, and S. salivarius were not inhibited. Thus, Ldh mutant strain 044 possesses a number of desirable traits that suggest it should be investigated further as a possible effector strain for replacement therapy of dental caries. These traits include its stability and low cariogenicity in the sensitive gnotobiotic rat caries model, its bacteriocinlike activity against certain other cariogenic S. mutans (but not against more inocuous indigenous oral streptococci), and the fact that it is a member of the most prevalent human serotype of cariogenic streptococci. PMID- 2917789 TI - Influence of Lsh, H-2, and an H-11-linked gene on visceralization and metastasis associated with Leishmania mexicana infection in mice. AB - Visceral infection and metastatic lesion development following intravenous or subcutaneous inoculation of Leishmania mexicana amastigotes were examined in different B10 congenic mouse strains carrying alternative alleles at Lsh, H-2, or H-11. The results show that, despite a failure to observe any differences in rates of expansion of primary lesions in mice inoculated subcutaneously, each of these genes could be shown to exert some influence during visceralization and metastatic spread of L. mexicana infection. Of particular interest were (i) the continuous advantage observed throughout 160 to 200 days of infection in Lshr versus Lshs mice, (ii) the association between structural gene polymorphism at H 2 and profound visceral and metastatic spread of the parasite producing disease phenotypes akin to diffuse cutaneous leishmaniasis and post-kala-azar dermal leishmaniasis in humans, and (iii) similar effects observed in mice differing at H-11, the functional basis for which involves modified expression of major histocompatibility complex class II molecules. The results are discussed in relation to the human disease and the possibility that homologs for each of these genes regulate leishmanial infections in humans. PMID- 2917790 TI - Production and characterization of murine monoclonal antibodies to Histoplasma capsulatum yeast cell antigens. AB - Four monoclonal antibodies (MAbs) were produced by immunizing mice with a disrupted yeast cell homogenate of Histoplasma capsulatum. MAbs 1 and 2 reacted only with the yeast cell antigens of H. capsulatum and Blastomyces dermatitidis, whereas MAbs 3 and 4 showed broader cross-reactivity. MAb 3 cross-reacted with B. dermatitidis, Paracoccidioides brasiliensis, Sporothrix schenckii, and Candida albicans, and MAb 4 cross-reacted with B. dermatitidis, C. albicans, Coccidioides immitis, Aspergillus fumigatus, and Mycobacterium tuberculosis. All four MAbs exhibited unique specificity when reacted with three different strains of H. capsulatum (G217B, A811, and P-IN). MAb 1 belonged to the IgG2b subclass, MAb 3 belonged to the IgG1 subclass, and MAbs 2 and 4 belonged to the IgG3 subclass. MAbs 1, 2, and 3 formed bands in the Western immunoblot assay; the two dominant distinct bands had apparent molecular masses of 72 and 62 kilodaltons. PMID- 2917791 TI - Immunoglobulin M-dependent classical complement pathway activation in killing of Pentatrichomonas hominis. AB - Complement pathway activity in the killing of Pentatrichomonas hominis was investigated in this study. At 10(5) organisms per ml, P. hominis was completely killed by the presence of 1% normal human serum. In contrast, no killing effect on P. hominis was observed when specific antibodies were absorbed or when the complement was destroyed. Moreover, Mg2+-ethylene glycol-bis-(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid-treated serum had no killing effect on P. hominis, while serum heated at 50 degrees C or treated with zymosan killed P. hominis as well as did normal human serum. Further study using gel filtration (Sephacryl S-300) and affinity chromatography (protein A) revealed that immunoglobulin M (IgM; 20 micrograms/ml) alone was responsible for the complement activation in the killing of P. hominis, but both IgA (24 micrograms/ml) and IgG (180 micrograms/ml) had no effect on complement-mediated lysis. On the other hand, IgG at 1,260 micrograms/ml completely inhibited complement-mediated killing by IgM, suggesting that a blocking factor is present in IgG. The results of this study indicate that a mechanism of IgM-dependent classical complement pathway activation contributes to the killing effect of normal human serum on P. hominis. PMID- 2917792 TI - Ureaplasma urealyticum pneumonia: experimental production and demonstration of age-related susceptibility. AB - Two different strains of Ureaplasma urealyticum isolated in pure culture from the lungs of newborn human infants were shown to produce an acute, self-limiting, interstitial pneumonia in newborn C3H/HeN and C57BL/6 mice that were free of other respiratory pathogens. Lesion severity peaked 3 to 6 days following intranasal inoculation of ureaplasmas and was resolved by 12 days. Rhinitis and otitis also occurred but did so less frequently than pneumonia. Organisms were localized within the alveoli in areas of inflammation. In comparison with newborn mice, 14-day-old mice were less susceptible to either colonization or disease. PMID- 2917793 TI - Experimental cecitis in gnotobiotic quails monoassociated with Clostridium butyricum strains isolated from patients with neonatal necrotizing enterocolitis and from healthy newborns. AB - Using axenic quails fed a diet containing lactose, we have investigated the potentially pathogenic roles of six Clostridium butyricum strains of human origin. Three strains (CB155-3, CB1002, and CB203-1) isolated from neonatal necrotizing enterocolitis patients and two of three strains (CB19-1 and CB25-2) isolated from healthy newborns led to cecal or crop lesions or both similar to those observed in human neonatal necrotizing enterocolitis: thickening of the cecal wall with gas cysts, hemorrhagic ulcerations, and necrotic areas. The lactose-negative strain (CB46-1) did not develop any lesions. The neuraminidase producing strain (CB155-3) caused lesions in all monoassociated quails, whereas the other strains caused lesions in 28 to 85% of animals. Removal of dietary lactose suppressed all pathological incidence. These results show that lactose fermentation is a prerequisite in these pathological changes and stress the roles played by both the strain and the host in the expression of C. butyricum enteropathogenicity. PMID- 2917794 TI - Antigenic analysis of Campylobacter species and an intracellular Campylobacter like organism associated with porcine proliferative enteropathies. AB - Whole-cell and outer membrane preparations of Campylobacter mucosalis, C. hyointestinalis, C. jejuni, and C. coli isolated from porcine intestines were compared with preparations of intracellular Campylobacter-like organisms extracted directly from the lesions of pigs with proliferative enteropathy. By gradient polyacrylamide gel electrophoresis, outer membrane and total protein profiles of C. mucosalis, C. hyointestinalis, C. jejuni, and C. coli were significantly different from each other and from those of the Campylobacter-like organisms. Immunoblotting of these preparations with rabbit antisera or monoclonal antibodies prepared against the intracellular Campylobacter-like organisms showed strong reactions only with a 25,000- to 27,000-molecular-weight component of preparations of the intracellular organisms. Antisera to cultivable Campylobacter species isolates did not react with preparations of intracellular organisms. Isoelectric focusing of sonicated preparations showed protein profile differences and an immune-reactive component in the intracellular organisms with a pI of 4.5. This study suggests that the intracellular Campylobacter-like organism associated with proliferative enteropathy may be a novel bacterium with significant antigenic differences from the Campylobacter species previously associated with the disease. PMID- 2917795 TI - Identification and localization of cyst-specific antigens of Giardia lamblia. AB - We induced Giardia lamblia trophozoites to encyst in vitro by exposure to conditions which are specific to the human small intestinal milieu. We now show that encystation entails the appearance of two new groups of antigens detected in Western blots by rabbit antiserum against cysts which had been purified from human feces. A heterodisperse group of lower-molecular-mass antigens (approximately 21 to 39 kilodaltons) was expressed relatively early (less than 19 h) in encystation. In contrast, discrete bands at approximately 66, 78, 92, and 103 kilodaltons only appeared after 24 h of incubation under conditions which lead to production of large numbers of water-resistant cysts. We also describe for the first time the appearance of prominent cytoplasmic vesicles, which were the earliest morphologic change in encysting trophozoites observable by light microscopy. Early in encystation, cyst wall antigens were concentrated in these vesicles, as shown by immunocytochemistry, suggesting that the vesicles function in export of cyst wall constituents. PMID- 2917797 TI - Hemagglutination activity of Campylobacter pylori. AB - Forty-five strains of Campylobacter pylori isolated from gastric biopsy specimens showed distinct hemagglutination activity. The activity was partially decreased by treatment with heat, trypsin, or an alkylating agent and was inhibited by porcine gastric mucin but not by various compounds, including D-mannose. PMID- 2917798 TI - Type of alcoholic beverage and oral cancer. AB - The effect on oral cancer risk of different types of alcoholic beverage was investigated using data from a hospital-based case-control study. Owing to the small numbers of subjects drinking one beverage exclusively, it was necessary to classify drinkers as consumers of predominantly beer, wine, or hard liquor (i.e., more than 50% of their whiskey equivalents of alcohol derived from a specific beverage). The number of predominantly wine drinkers was too small to permit analysis. Logistic regression was used to obtain estimates of the risk associated with each predominant beverage, with adjustment for other risk factors and confounding variables. In males, the odds ratio for predominantly beer drinkers increased with increasing level of intake, reaching 4.87 (95% confidence interval: 2.51-9.46) in drinkers of 7+ oz. of whiskey equivalents/day. The odds ratio for predominantly hard liquor drinkers showed a similar increase, reaching 5.74 (95% confidence interval: 2.94-11.22) in predominantly hard liquor drinkers consuming 7+ oz. of whiskey equivalents/day, suggesting that the effect of these 2 major types of alcoholic beverage is of similar magnitude. The trends were less clearcut in women due to small numbers of drinkers. PMID- 2917796 TI - Binding of cholera toxin to pig intestinal mucosa glycosphingolipids: relationship with the ABO blood group system. AB - A search for compounds from intestinal mucosa of pigs carrying and not carrying blood group A-active substances (A+ and A- pigs, respectively) capable of binding cholera toxin (CT) was performed. Glycolipid extracts from a pool of pig intestinal mucosa resolved in thin-layer chromatography (TLC) revealed the presence of six to eight compounds capable of binding 125I-CT, two of them running as the ganglioside standards GM1 and GD1b. When intestinal mucosa glycolipids from single pigs were assayed by TLC for CT-binding capacity, two different patterns of labeling were observed. The main difference was at the level of compounds running below GD1b. The A+ pigs but not the A- pigs showed CT binding at this level. The major CT-binding compound detected only in A+ pigs was purified and some properties were determined. After TLC developed with different solvent systems, the purified compound bound CT and also immunoreacted with anti A and anti-AB antisera but not with anti-B antiserum. The compound was also able to inhibit the hemagglutination of human A erythrocytes caused by anti-A antiserum, but inhibition was not observed with the B-anti-B or O (H)-Ulex europaeus lectin systems. A partial chemical characterization indicated that the active compound is a neutral glycosphingolipid containing glucose, fucose, galactose, and hexosamine. The existence of a blood group-active substance(s) able to interact with CT may help to explain the relationship between ABO blood groups and the diarrheal disease caused by infection with Vibrio cholerae. PMID- 2917799 TI - Screening for breast cancer in Nijmegen. Report of 6 screening rounds, 1975-1986. AB - A population-based screening programme for breast cancer was initiated in Nijmegen in 1975 with mammography as the only screening procedure. Up to January 1987, 6 screening rounds were carried out with a 2-year screening interval. Rates of attendance, referral, biopsy and detection were calculated and numbers of interval cancers are presented in order to give a clear view of what repeated screening can accomplish in a population. At the first screening round the attendance rate was 87% for women under age 50 and 83% for women aged 50-64. For women aged 65 or over the initial attendance rate was 40%. Rates of attendance declined in subsequent years. Detection rates were highest for elderly women at their first examination: 9.5 per 1,000 screened women. Corresponding rates were 5.6 and 2.3 per 1,000 for women aged 50-64 and below 50 respectively. The positive predictive value for referral was, on average, 20% for women under age 50 and 50% for elderly women, although a sharp increase was seen in the last 2 screening examinations for all age-groups. Predictive values for biopsy were higher: 30% on average for women aged under 50 and 60%-70% for elderly women, again with a sharp increase in the last 2 screening rounds. Interval cancer rates, calculated as the number of cancers occurring within 2 years among negatively screened women at risk, showed no particular trend and varied between 0.9-1.3 per 1,000 woman-years after each screening round. Compared to screen detected cancers, interval cancers occurred more frequently in younger women. In women under age 50, the ratio between screen-detected and interval cancer was about 1:1, while it was about 2:1 for elderly women. PMID- 2917800 TI - Elevated apolipoprotein(a) levels in cancer patients. AB - Elevated plasma lipoprotein(a) has been associated with an increased risk of cardiovascular disease. We report a significant elevation of total plasma apolipoprotein(a) levels in cancer patients compared with hospitalized control patients and normal healthy blood donors. Of the cancer patients studied, 48% had levels in excess of 350 mg/l compared to 20% in normal blood donors and 29% of hospitalized control patients. The elevation was more prevalent but less extreme than that reported in patients with cardiovascular disease. Density gradient centrifugation studies of plasma from cancer patients revealed the presence of apolipoprotein(a) at a density of 1.085 g/ml in the region where mRNA-containing proteolipids, neoproteolipids and malignancy-associated lipoproteins had previously been isolated. PMID- 2917801 TI - Time trends in cancer mortality in the Federal Republic of Germany: progress against cancer? AB - In accordance with a previous analysis of US cancer mortality, this report also indicates that cancer mortality in the FRG over the last 3 decades (1952-1985) has not shown any decline commencing in a given period and prevailing in all age groups. If present, such effects could have been interpreted as a manifestation of improvements associated with cancer treatment. The absence of such an effect, derived by using data up to 1985 and age-specific mortality rates, supports the view expressed in the US analysis that improvements in cancer treatment are unlikely to have an impact on overall cancer mortality statistics and that efforts toward prevention may be more rewarding. PMID- 2917802 TI - Modelling the risk of adult T-cell leukemia/lymphoma in persons infected with human T-lymphotropic virus type I. AB - Adult T-cell leukemia/lymphoma (ATL), a malignancy of mature CD4-positive lymphocytes, has been etiologically linked to the human retrovirus HTLV-I. Although a long latent period is suggested from migrant studies, little prospective information on the risk of developing ATL among persons with HTLV-I infection is available. We present here a model for ATL risk based upon age- and sex-specific HTLV-I seroprevalence data from a cross-sectional survey of 13,000 Jamaicans and ATL incidence data from a 2 1/2-year case-control study. By examining the age-specific incidence of ATL relative to both adult and childhood acquired seropositivity versus childhood-acquired seropositivity alone, we provide evidence in support of the hypothesis that childhood infection with HTLV I is important to the development of ATL. Using this model, the cumulative lifetime risk of ATL for those infected before age 20 is estimated to be 4.0% for males and 4.2% for females. Under this hypothesis, HTLV-I-associated diseases with shorter latent periods, such as tropical spastic paraparesis, should have a higher incidence in adult females than in adult males. PMID- 2917803 TI - Suppression of transformation and immortality in human/Chinese hamster fibroblast hybrids--a model for suppressor gene isolation. AB - Somatic cell hybrids were produced by fusion of normal human (foreskin) fibroblasts and a transformed Chinese hamster fibroblast line V79-8. Overall, approximately 30% of hybrid clones showed stable reversion to normal morphology and growth control in vitro as shown by serum and anchorage dependence. In one third of these clones, senescence was observed after a number of generations similar to that required for the human fibroblast parent cells to senesce. The remainder appear to be immortal. Normal human chromosomes can therefore restore growth control with or without finite life-span to this transformed cell. V79 cells were found to be transfectable at an efficiency compatible with detection of single-copy gene transfer from genomic DNA. Furthermore, these cells were exceptionally sensitive to negative ("suicide") selection. Taken together, our data suggest that the V79 line represents an ideal system for isolation of human tumour suppressor genes. PMID- 2917804 TI - Differential expression of N-myc and c-src proto-oncogenes during neuronal and schwannian differentiation of human neuroblastoma cells. AB - Neuroblastoma (NB) cells can be induced to differentiate bidirectionally into either neuronal or schwannian cells by different inducers. However, the underlying mechanisms are poorly understood. We examined the expression of N-myc and c-src genes in 3 human NB-cell lines during either neuronal or schwannian differentiation in vitro, since proto-oncogenes are considered to play a pivotal role in regulating cell proliferation and differentiation. Decreased N-myc expression and increased c-src expression were observed during neuronal differentiation by retinoic acid, polyprenoic acid (E5166) and dibutyryl cyclic AMP, whereas the expression of N-myc and c-src genes was considerably reduced during schwannian differentiation by bromodeoxyuridine, demonstrating that the expression of N-myc and c-src genes was regulated independently in the bipolar differentiation processes of NB cells. Our results suggest that enhanced N-myc expression might be closely linked to the undifferentiated phenotypes of NB cells, that c-src expression might be related to the neuronal differentiation of NB cells, and that N-myc and c-src genes might be regulated independently in the determination of the bipolar differentiation of NB cells. PMID- 2917805 TI - In vitro proliferative responses of spleen lymphocytes from rats bearing progressive or regressive tumors induced by cell variants of a syngeneic colon carcinoma. AB - From one colonic carcinoma chemically induced in the rat, 2 sublines of tumor cells have been cloned, one (PROb) inducing progressive tumors, the other (REGb) generating tumors that regress a few weeks after s.c. injection into syngeneic hosts. Our study was aimed at comparing cellular immunity between animals bearing PROb or REGb tumors. Spleen cells were first tested for in vitro proliferation in response to mitomycin-treated PROb or REGb cells. Only spleen cells from rats injected with REGb cells proliferated significantly when mixed with PROb or REGb cells. The proliferative response induced by REGb cells was considerably higher than the response to PROb cells. When spleen cells from rats bearing REGb tumors were cultured with a mixture of REGb and PROb cells at various PROb/REGb cell ratios, PROb cells significantly suppressed the strong proliferative response generated by the same number of REGb cells alone. REGb-immune spleen cells, after in vitro stimulation by PROb or REGb cells, were not cytotoxic for either cell variant. REGb-immune spleen cells did not differ in their content of T lymphocytes expressing CD4 or CD8 markers when they were stimulated by PROb or REGb cells in vitro, but REGb cells induced a larger number of activated lymphocytes expressing the IL-2 receptor. Our results indicate that, compared to REGb cells, PROb cells are poorer stimulators of proliferation of tumor-immune spleen cells, and that they are able to suppress the proliferative response induced by REGb cells. PMID- 2917806 TI - Sulzberger-Garbe disease in Europe. PMID- 2917807 TI - Spironolactone therapy in hirsute women. PMID- 2917808 TI - Cutaneous sarcoidosis and tribal scarifications in West Africa. AB - Sarcoidosis is quite common in American and West Indian blacks. In America, the incidence in blacks could be up to 10 times higher than in whites. Sarcoidosis is generally believed to be rarer in African blacks and especially along the West African coast from which the American blacks trace their ancestry. The difference in incidence may be due to environmental influences, poor reporting system from inadequate local awareness of the presentation, confusion with tuberculosis, and lack of the Kveim antigen. Diagnosis of sarcoidosis is most commonly made from the pulmonary and skin manifestations. Since the skin manifestation presents readily for observation without the need for costly devices like x-ray machines, the present study focused on and analyzed the seven cases seen in the skin clinic within a period of 2 years (an incidence of 0.85%), showing that the commonest presentation was as scar-sarcoid on longstanding tribal marks. Tribal scarification is common in West Africa, and one should investigate any change in a longstanding scar. This heightened awareness in areas where scarification is or was practiced could end the belief of the rarity of sarcoidosis in the West African subregion. PMID- 2917809 TI - Radiation-induced soft tissue osteogenic sarcoma of the scalp. PMID- 2917810 TI - Exudative discoid and lichenoid chronic dermatosis (Sulzberger-Garbe). A fictional disease? PMID- 2917811 TI - Sulzberger-Garbe dermatosis in an Indian patient. PMID- 2917812 TI - Therapy of tinea nigra plantaris. AB - Four cases of tinea nigra plantaris are presented. The therapeutic approaches used by different dermatologists who treated these patients are analyzed in order to obtain a meaningful conclusion on how to best manage this infrequent entity. We conclude that the visible affected skin should be scraped off before using either ciclopiroxolamine or an imidazole topically; systemic therapy is not recommended. PMID- 2917813 TI - Secondary syphilis treated with parenteral cephalosporin. PMID- 2917814 TI - Transient acantholytic dermatosis treated with isotretinoin. PMID- 2917815 TI - Exudative discoid and lichenoid chronic dermatitis: does it exist or should it be discarded? PMID- 2917816 TI - Pediatric ophthalmology. PMID- 2917817 TI - Botulin therapy in pediatric ophthalmology. PMID- 2917818 TI - Detection and treatment of infantile cataracts. PMID- 2917819 TI - Comparative myocardial uptake characteristics of hexakis (alkylisonitrile) technetium(I) complexes. Effect of lipophilicity. AB - Hexakis (alkylisonitrile) technetium(I) complexes are a new class of cationic, lipophilic myocardial perfusion imaging agents. To further evaluate the effect of lipophilicity on myocardial uptake characteristics, the authors systematically synthesized and tested Tc-isonitrile complexes of varying lipophilicity in both cellular and whole animal systems. In chick heart cells in monolayer culture, cellular plateau level uptake in general correlated with lipophilicity of the complexes (determined by reverse phase high performance liquid chromatography) (r = .71) as well as with scintigraphic intensity of imaged rabbit hearts (r = .91). Exceptions to this trend indicated that additional factors such as size of the complex and form of the terminal alkyl chain branching also may have influenced uptake. The data indicated that neither the lipophilic properties nor the cation charge alone were sufficient to predict myocardial uptake. In addition, intravenous injection of complexes into rabbits showed optimal myocardial images with agents of intermediate lipophilicity. Results indicated that, following intravenous administration, complexes of low lipophilicity yielded suboptimal myocardial images because of low heart cell uptake, whereas complexes of high lipophilicity yielded poor relative myocardial visualization because of excessive binding to additional organs and compartments. PMID- 2917820 TI - Scatter compensation in digital chest radiography using Fourier deconvolution. AB - The authors present a numerical deconvolution technique to compensate for image degrading effects caused by scattered photons in radiographic chest images. Fourier transform techniques are used to deconvolve a shift invariant model of the two dimensional point spread response functions of the scattered radiation. This approach uses a digitized radiograph acquired with a standard chest imaging protocol, so no specialized imaging equipment is required. While the shift variant shape of the scatter model is optimized for the lung field, effective compensation is provided when this model shape is applied to other chest regions. Preliminary evaluation suggests that this technique can provide improved image contrast over the entire chest region. PMID- 2917821 TI - Intravascular contrast media and the blood-brain barrier. Testing the new nonionic agent ioxilan. AB - The effects of diatrizoate, iohexol, and ioxilan on the blood-brain barrier (BBB) were investigated in normal and hypertensive rats. Anesthetized Wistar rats received 14C-inulin as an indicator for BBB disruption. Diatrizoate, iohexol, or ioxilan (350 and 175 mgI/mL) or normal saline was then injected into the carotid artery (2 mL in 30 seconds). Twenty minutes later, the cardiovascular system was flushed, the brain removed, and each hemisphere was digested. BBB disruption, expressed as counts/minute/mg protein, was compared for each hemisphere in each group by analysis of variance. BBB damage in the diatrizoate-350 group was significantly greater than that in all other groups. No significant BBB damage resulted from iohexol or ioxilan relative to normal saline. PMID- 2917822 TI - Rapid, contrast-enhanced, diuretic magnetic resonance imaging of unilateral partial ureteral obstruction. An experimental study in micropigs. AB - The value of rapid, contrast-enhanced, diuretic magnetic resonance (MR) imaging (using ferrioxamine B and furosemide) in demonstrating partial unilateral ureteral obstruction and the potential of such MR imaging in differentiating obstructive from nonobstructive hydronephrosis was assessed in six micropigs. MR imaging (0.35 Tesla, partial-flip technique with repetition time [TR] of 125 milliseconds, echo-delay time [TE] of 20 milliseconds, and flip angle of 70 degrees) was performed before, and at 5, 12, and 19 days after partial ureteral obstruction. Additionally, MR images were acquired 5, 12, and 19 days after release of obstruction. The diuretic was injected 10 minutes after the contrast medium. MR findings were correlated with results from nuclear scintigraphy (99mTc DMSA uptake). MR images provided good morphologic detail from which renal size, parenchymal thickness, and degree of hydronephrosis could be determined. Contrast medium allowed assessment of cortical uptake and urinary excretion. The course of cortical signal enhancement best characterized the difference between obstructive and nonobstructive hydronephrosis. Normal kidneys and kidneys with nonobstructive hydronephrosis showed progressive decrease in cortical signal enhancement (-11.7% within 40 minutes) after furosemide injection. The kidneys with obstructive hydronephrosis demonstrated a plateau of signal enhancement without decrease ( 0.7% within 40 minutes). These results demonstrate the utility of rapid contrast enhancing, diuretic MR imaging in differentiating obstructive from nonobstructive hydronephrosis. PMID- 2917823 TI - Chemical shift imaging of atherosclerosis at 7.0 Tesla. AB - Chemical shift imaging (CSI) was performed on cadaveric atherosclerotic fibrous plaques, periaortic adipose tissue, and cholesterol standards using a 7.0 Tesla horizontal bore prototype imaging spectrometer. Proton spectroscopy of intact tissue and deuterated chloroform extracted samples was done at the equivalent field strength of 7.0 Tesla on a vertical bore spectrometer, including studies of temperature dependence and T2 relaxation measurements. Spectra obtained using CSI on the imaging magnet were comparable with those from the conventional vertical spectrometer. Fibrous plaques and adipose tissue had unique spectral features, differing in the ratios of their water and various fat components. Chloroform extractions revealed a typical cholesteric ester spectrum for the fibrous plaque in contrast to the triglyceride spectrum of the adipose tissue. These two tissues also had different T2 relaxation measurements of their major fat resonances, with fibrous plaques having a short T2 compared to adipose tissue (15.9 milliseconds vs. 46.2 milliseconds). Temperature dependence studies showed that spectral signal intensity of the fat resonance of the fibrous plaque increased while linewidth decreased with increasing temperature from 24 degrees C to 37 degrees C. Atherosclerotic lesions may be studied at 7.0 Tesla, and NMR parameters defined in the present study may be used for further studies at other magnetic field strengths. PMID- 2917824 TI - Measurement of cerebrospinal fluid movement in the spine. An experimental technique. AB - The authors devised a new technique for measuring cerebrospinal fluid movement in the spine. With gated list mode acquisition of radioactive emissions, bulk flow, oscillations, and dispersion of a bolus of isotope can be measured. The accuracy of the technique was measured in a simulation in which fluid oscillated at 71 cycles/minute and displaced at 6.5 cm/minute. With this method, the measured oscillation frequency and amplitude and the rate of translation were within 10% of actual values. PMID- 2917825 TI - MRI of the athletic knee. Findings in asymptomatic professional basketball and collegiate football players. AB - For the dedicated athlete in whom minor injuries are frequent and major injuries relatively common, a noninvasive knee assessment could either obviate the need for arthroscopy or focus its direction. The opportunity to study asymptomatic athletes was not feasible before the advent of magnetic resonance imaging (MRI). In this preliminary work, we examined 40 knees in 20 asymptomatic volunteer athletes, including five professional basketball players and 15 collegiate football players. Images were obtained at 0.5 T or 1.5 T. Spin echo sequences were used to obtain 5.0 mm thick coronal and sagittal sections. Fifty percent of asymptomatic athletes (10/20) had significant baseline MRI abnormalities that could have adversely affected scan interpretation in the context of an acute injury. Half of these athletes with MRI abnormalities, or 25% of the total (5/20), had no previous surgery and were unaware of significant injury. PMID- 2917826 TI - Pax. PMID- 2917827 TI - Medical student attitudes toward radiology. A multi-institutional survey. AB - A questionnaire was administered to 238 students at four institutions before and after a radiology clerkship to evaluate student attitudes regarding radiology as a career, radiologist expertise, and clerkship expectations. There was no statistically significant difference among the clerkships, although they varied in types of experience, geographic location, and size. After the clerkship, the students agreed more strongly that the radiologist should be involved in patient workup, screening of requests, interpretation of emergency room films, and consultations. A significant change in attitude could be identified after the four-week experience, indicating a desire for the radiologist to have a more active role as imaging consultant. PMID- 2917828 TI - As the world turns. PMID- 2917829 TI - Reproducibility in the analysis of multigated radionuclide studies of left ventricular ejection fraction. AB - The authors determined the reproducibility (the standard deviation [SD]) in the analysis of multigated radionuclide studies of left ventricular ejection fraction (LVEF). Radionuclide studies from a consecutive series of 38 patients suspected of ischemic heart disease were analyzed independently by four nuclear medicine physiologists and four laboratory technicians. Each study was analyzed three times by each of the observers. Based on the analyses of the eight observers, the SD could be estimated by the use of a variance component model for LVEF determinations calculated as the average of the analyses of an arbitrary number of observers making an arbitrary number of analyses. This study presents the SDs for LVEF determinations based on the analyses of one to five observers making one to five analyses each. The SD of a LVEF determination decreased from 3.96% to 2.98% when an observer increased his number of analyses from one to five. A more pronounced decrease in the SD from 3.96% to 1.77% was obtained when the LVEF determinations were based on the average of a single analysis made by one to five observers. However, when dealing with the difference between LVEF determinations from two studies, the highest reproducibility was obtained if the LVEF determinations at both studies were based on the analyses made by the same observer. No significant difference was found in the reproducibility of analyses made by nuclear medicine physicians and laboratory technicians. Our study revealed that to increase the reproducibility of LVEF determinations, special efforts should be made to standardize the outlining of the end-systolic region interest. PMID- 2917830 TI - A large animal model (swine) to study the diagnosis and treatment of cholelithiasis. AB - Human gallstones were surgically placed into the gallbladders of 200 swine. Eight of these swine were used as a prospective series to verify that the placement and presence of human gallstones in their gallbladders caused no significant pathologic changes in the gallbladder and that the gallstones were not spontaneously dissolved. Although limitations exist, the advantages of this procedure demonstrate that the surgically prepared swine is an appropriate model for controlled in vivo experiments in radiologic imaging or interventional treatment. A 4 F pig-tailed catheter designed for Trocar insertion was developed as a companion to this model. PMID- 2917831 TI - Reevaluation of indications for percutaneous placement of the Greenfield filter. AB - In our institution twice as many Greenfield filters were inserted in the year after percutaneous placement was begun as in the previous year when all filters were surgically inserted. Review of the indications for surgical and percutaneous filter placement in our hospital reveals that more filters were inserted percutaneously for all indications except recurrent emboli. The rates of percutaneous and surgical filter insertion for prophylaxis with acute deep venous thrombosis were similar (40% and 42%, respectively) and were higher than the majority of reported filter series because of the large number of high risk patients in our hospital population. In evaluating each patient for risk factors concerning the development of venous thromboembolism, the contraindications to anticoagulation, and the effectiveness and possible complications of anticoagulant therapy, we have defined a much broader range of patients as candidates for Greenfield filter insertion than had been considered in our institution in the past. PMID- 2917832 TI - Contrast and accuracy of relaxation time measurements in acquired and synthesized multislice magnetic resonance images. AB - The effects of interslice spacing, the number of data points and other factors on the accuracy of relaxation time measurements and contrast have been investigated for both acquired and synthesized multislice MR images using experiments and computer simulations. The cross-excitation between adjacent slices in multislice imaging affects both contrast and derived relaxation times. Such measurements also are affected by the T1 and T2 of the materials imaged, the pulse sequence timing parameters, and the number of data points used to estimate the relaxation times. Errors in T1 and T2 may be severe, particularly for slice spacings less than 0.5 slice thickness and for long T1 and T2 materials. Consequently, the difference in signal intensities between two materials with different relaxation times also varies with slice spacing and between acquired and synthetic images, particularly for strongly T1-weighed images. PMID- 2917833 TI - Ioversol. Double-blind study of a new low osmolar contrast agent for peripheral and visceral arteriography. AB - The new low-osmolar contrast agent ioversol was compared with the conventional ionic contrast agent diatrizoate in 60 patients undergoing routine abdominal (21 patients) and peripheral (39 patients) arteriography. The effects on hemodynamics, various laboratory parameters, and patient comfort were evaluated. In peripheral arteriography, there was less discomfort with ioversol as well as decreased magnitude and incidence of hypotension (P less than .001) after injection. In visceral arteriography, there was no significant difference between the two agents. Overall, the incidence of ECG changes was small in both groups (ioversol 2%, diatrizoate 8%). The two media were equivalent in incidence of adverse reactions (eg, nausea, vomiting, urticaria), the effect on laboratory parameters, and in the diagnostic adequacy of the radiographs. We conclude that ioversol is safe and efficacious for peripheral and visceral arteriography. In peripheral arteriography it causes less patient discomfort and, perhaps more importantly, fewer hemodynamic alterations than diatrizoate. These differences in hemodynamic effects may be important in patients with hemodynamic instability or limited cardiovascular reserve. PMID- 2917834 TI - Effects of contrast media on neural tissue glucose uptake in vitro. AB - The authors previously showed that metrizamide causes an inhibition in CO2 production in rat neural tissue. The purposes of this work were to test if this inhibition was the result of a competitive inhibition of metrizamide with the D glucose transport system and to test the effect of other contrast media. Deoxyglucose was used as a marker for glucose. The first cellular system using rat hippocampus slices was designed to examine the effect of 15 mM and 80 mM metrizamide on deoxyglucose uptake. The second cell-free system, using isolated rat brain synaptosomes, was designed to evaluate more accurately the mechanism and kinetics of metrizamide's inhibitory effect on the uptake of deoxyglucose and to compare metrizamide to other nonionic contrast media (iohexol, iopamidol, iotrol, and iodixanol). These experiments demonstrate that there is inhibition of D-glucose uptake only in hippocampus slices and that the inhibition is dependent on the concentration of metrizamide. This does not, however, appear to be a competitive inhibitory effect on the carrier such as that between D-glucose and 2 deoxy-D-glucose. In synaptosomes, none of the contrast media had a significant effect on the uptake of 2-deoxyglucose. PMID- 2917836 TI - Taxation for using 'forbidden terms'. PMID- 2917835 TI - Exposure equalization technique in mammography. PMID- 2917838 TI - Almost perfect. PMID- 2917839 TI - Computer-assisted radiology resident rotation scheduling. AB - The author developed a method for computer-assisted scheduling of resident rotations in which the chief resident determines the most desirable set of rotations for each resident, disregarding specific month assignments except as required or requested, and the computer generates the schedule by assigning months to rotations. The computer uses an efficient search algorithm to find a schedule that satisfies all requirements. The method satisfies training goals, staffing needs, and residents' desires more effectively than manual scheduling. Although fixed staffing levels for every rotation are required, flexibility is achieved through "dummy" assignments of rotations to residents. PMID- 2917837 TI - Facial deformity and rash. PMID- 2917840 TI - Displays. Contrast and spatial requirements. PMID- 2917841 TI - Medical charts and malpractice: how to avoid costly errors and omissions. AB - A thorough and well-organized medical chart can prevent malpractice from occurring, discourages the filing of groundless lawsuits, and is a useful tool in defending a physician in a medical malpractice action. This paper suggests methods by which a physician may improve record keeping and minimizing medico legal exposure. PMID- 2917842 TI - Mortality and career radiation doses for workers at a commercial nuclear power plant: feasibility study. AB - Career radiation doses for 8,961 male workers at the Calvert Cliffs Nuclear Power Plant (CCNPP) were determined for both utility (n = 4,960) and contractor (n = 4,001) employees. Workers were followed from the time of first employment at CCNPP (including plant construction) to the end of 1984 (mean follow-up = 5.4 y). Plant operation began in 1975. The mean duration of employment was 1.9 y at CCNPP and 3.1 y in the nuclear industry. Career radiation doses were determined from dosimetry records kept by the utility company and the U.S. Nuclear Regulatory Commission (NRC). For all exposed workers, the average career dose was 21 mSv and was higher for contractor (30 mSv) than utility (13 mSv) workers. Career doses were also higher among those employed in the nuclear industry for greater than or equal to 15 y (111 mSv) and among workers classified as health physicists (56 mSv). Cumulative doses of greater than or equal to 50 mSv were received by 12% of the workers; the maximum career dose reported was 470 mSv. The availability of social security numbers for practically all employees facilitated record-linkage methods to determine mortality; 161 deaths were identified. On average the workers experienced mortality from all causes that was 15% less than that of the general population of the U.S., probably due to healthier members of the population being selected for employment. Our investigation demonstrates that historical information is available from which career doses could be constructed and that, in principle, it is feasible to conduct epidemiologic studies of nuclear power plant workers in the U.S. Although difficult, the approach taken could prove useful until such time as a comprehensive registry of U.S. radiation workers is established. PMID- 2917843 TI - Shielding requirements for constant-potential diagnostic x-ray beams determined by a Monte Carlo calculation. AB - A Monte Carlo calculation has been performed to determine the transmission of broad constant-potential x-ray beams through Pb, concrete, gypsum wallboard, steel and plate glass. The EGS4 code system was used with a simple broad-beam geometric model to generate exposure transmission curves for published 70, 100, 120 and 140-kVcp x-ray spectra. These curves are compared to measured three-phase generated x-ray transmission data in the literature and found to be reasonable. For calculation ease the data are fit to an equation previously shown to describe such curves quite well. These calculated transmission data are then used to create three-phase shielding tables for Pb and concrete, as well as other materials not available in Report No. 49 of the NCRP. PMID- 2917844 TI - Preliminary experiences with 222Rn gas in Arizona homes. AB - Results of a survey of 222Rn gas using four-day charcoal canister tests in 759 Arizona homes are reported. Although the study was not random with respect to population or land area, it was useful in identifying areas at risk and locating several homes having elevated indoor 222Rn air concentrations. Approximately 18% of the homes tested exceeded 150 Bq m-3 (4 pCi L-1), with 7% exceeding 300 Bq m-3 (8 pCi L-1). Several Arizona cities had larger fractions of homes exceeding 150 Bq m-3 (4 pCi L-1), such as Carefree and Cave Creek (23%), Paradise Valley (30%), Payson (33%), and Prescott (31%). The Granite Dells and Groom Creek areas of Prescott had in excess of 40-60% of the houses tested exceeding 150 Bq m-3 (4 pCi L-1). Elevated 222Rn concentrations were measured for a variety of home types having different construction materials. Private well water was identified as a potentially significant source of 222Rn gas in Prescott homes, with water from one well testing over 3.5 MBq m-3 (94,000 pCi L-1). A 222Rn concentration in air exceeding 410,000 Bq m-3 (11,000 pCi L-1) was measured using a four-day charcoal canister test in a house in Prescott which had a well opening into a living space. Additional measurements in this 150-m3 dwelling revealed a strikingly heterogeneous 222Rn concentration. The excessive 222Rn level in the dwelling was reduced to less than 190 Bq m-3 (5.2 pCi L-1) by sealing the well head with caulking and providing passive ventilation through a pipe. PMID- 2917845 TI - Radon concentrations in five Pennsylvania soils. AB - The Rn concentration in the interstitial soil air depends on the Rn emanation from the soil, the water content of the soil, and the volume of the interstitial air space. The Rn emanation, which depends on the type of soil and the water content of the soil, can vary greatly from soil to soil. The interstitial air space depends on the soil compaction and the water content of the soil, so the Rn concentration can vary greatly from one soil type to another as well as within a given soil type. The emanation characteristics and soil compactions are studied for five Pennsylvania soils and ranges of possible Rn concentrations are calculated. Possible Rn concentrations in the soils studied range from about 20 kBq m-3 to nearly 1 MBq m-3. PMID- 2917846 TI - On improving the validity of wire screen "unattached" fraction Rn daughter measurements. AB - Wire screens are commonly used to estimate "unattached" Rn daughter fractions in ambient and mine atmospheres. However, it is now recognized that the "unattached" fraction is in reality an ultrafine cluster mode in the 0.5-3 nm size range and that the collection efficiency versus particle diameter characteristics of wire screens do not permit a distinct separation of the "unattached" and "attached" fractions. Wire screen penetration theory and a semi-empirically corrected diffusion coefficient equation are used to characterize "unattached" fraction measurements as a function of experimental parameters. Collection efficiency curves are estimated for previously published wire screen "unattached" fraction measurements, and improvements in wire screen methods for such measurements are discussed. PMID- 2917847 TI - Correlation between airborne U exposure and U urinalysis results at Bear Creek Uranium. AB - Inhalation exposure history and U urinalysis data collected at Union Pacific Resources Company's Bear Creek Uranium milling operation, located in the Powder River Basin area of Wyoming, were studied to determine if a correlation could be made between airborne U exposure and U urinalysis results. It was observed from these data that U urinalysis results correlate with airborne U exposure levels when averaged over a period of time. The urinary U excretion rate, empirically derived from these data, was 1.8 X 10(-1) micrograms U in urine d-1 per micrograms U inhaled d-1 for samples collected after 2.9 d of no exposure. PMID- 2917848 TI - Changes in per capita and collective dose equivalent due to natural radiation in Taiwan (1950-1983). AB - This paper deals with the changes in per capita and collective dose equivalent in Taiwan in the past three decades based on the measured terrestrial and cosmic radiation levels and the population distribution as well. Over 70% of the population is concentrated in three population centers which have been naturally formed in the north, middle and south of Taiwan along the west coast as a result of industrialization and population growth. The population has increased 2.5 times in the past 33 y and reached to 1.9 X 10(7) persons, yet the migration of population was from the rural areas where the natural radiation is usually high to the urban areas where the natural radiation is usually low. The resulting collective dose equivalent has been increasing, yet the per capita dose equivalent, on the contrary, has been decreasing. PMID- 2917849 TI - Some effects of radiation dosimetry errors on an estimated dose-response relationship. PMID- 2917850 TI - Essential trace metal concentrations in beagle liver and bone tissue after prolonged Zn-DTPA treatment. PMID- 2917851 TI - Particle size distributions for airborne radionuclides in Ginna steam generator work environments. PMID- 2917852 TI - Transfer to milk of 131I and 137Cs released during the Chernobyl reactor accident. PMID- 2917853 TI - Cesium-137 levels in breast milk and placentae after fallout from the reactor accident at Chernobyl. PMID- 2917854 TI - Determining the ratio of 239Pu to 241Am in wounds by measuring the L gamma x-rays with a Si(Li) detector. AB - A Si(Li) planar detector provides sufficient photopeak resolution to resolve the 20.16-keV U L gamma x rays resulting from 239Pu decay and the 20.78-keV Np L gamma x rays resulting from 241Am decay. The energies and, therefore, the absorption coefficients of the two x rays are very similar; thus, the ratio of the peaks for a source embedded in tissue remains approximately the same for the two x rays up to at least 6 mm. Measurements of 239Pu-to-241Am ratios by this method in deep wounds agree with results obtained by radiochemical analysis of excised tissue. PMID- 2917855 TI - Accidental CT scanning without A1 filtration and its dosimetry. PMID- 2917856 TI - Correction to BEIR IV report. PMID- 2917857 TI - Nuclear medicine staff and patient doses in Manitoba (1981-1985). AB - The number of diagnostic in vivo nuclear medicine (NM) procedures in the Province of Manitoba (population 1 million) has been examined over the period 1981 to 1985. The annual number of procedures performed has remained relatively constant at about 25 per thousand population. The isotope 99mTc accounted for 86% of all the studies performed and the number of NM procedures per imaging system was approximately 1,300 per annum. The total number of NM operators in the province increased from 30 in 1981 to about 40 in 1985. The mean NM operator dose was reduced from 3.8 mSv to 2.5 mSv over this five-year period and the collective operator dose underwent a smaller reduction of 13% to about 100 person-mSv in 1985. The value of the mean patient effective dose equivalent (HE) was relatively constant at 5.2 mSv. The contribution of diagnostic NM procedures to the annual per caput population dose in Manitoba was 0.13 mSv. Three diagnostic procedures (brain, bone and cardiac) accounted for approximately 80% of the collective patient HE. Patient profiles (age, sex and medical history) were obtained for the patients undergoing these three procedures, which showed them to be atypical in comparison to a normal working population. These data suggested that the application of the International Commission on Radiological Protection risk factor of 1.65 X 10(-2) Sv-1 to this patient population would have significantly overestimated the expected radiation detriment. PMID- 2917858 TI - Exposure to electromagnetic fields in arc welding. AB - Electric and magnetic fields at the power line frequency (60 Hz) and its harmonics have been measured around 22 arc welders. The electric field strengths in most cases were very low (1 V m-1) and only for one device reached 300 V m-1. Magnetic flux densities ranged from a few microT to a few hundred microT (a few A m-1 to a few hundred of A m-1). Several devices surveyed produced high magnetic flux densities (200-400 microT), which are rarely encountered in the environment and are representative of high occupational exposures. PMID- 2917859 TI - An automated dosimetry system for microwave and thermal exposure of biological samples in vitro. AB - A waveguide exposure system with automated sample temperature measurement is described. This system provides on-line determination of the temperature profile over time of biological samples in vitro. It allows automated computation of the specific absorption rate determined from heating/cooling curves, uses minimally perturbing thermometry, is biocompatible and can be used for measurements of both microwave and conventional heating. PMID- 2917860 TI - Concentrations of U and Po in animal feed supplements, in poultry meat and in eggs. AB - The present study was undertaken to assess the contribution of phosphate feed supplements to the radiation exposure of the population in Israel. The phosphates usually contain appreciable quantities of U and its daughters and the actual exposure of human consumers depends, to a very large extent, on the degree of equilibrium of the decay chain in the feed and through the metabolic process. The concentrations of 238U, 234U, 226Ra and 210Po (210Pb) in poultry feed supplements and in chicken meat (breasts, thighs) and organs (livers, spleens, gizzards) as well as in eggs were determined. From the results, the transfer coefficients of U and Po in chicken meat and in eggs were calculated. The effective dose equivalent to the Israeli population due to the consumption of poultry products which accounts for approximately 70% of all meat consumed in Israel is assessed to be 0.04 mSv y-1. PMID- 2917861 TI - Quantitative scanning electron microscopic autoradiography of inhaled 239PuO2. AB - We have applied the scanning electron microscope (SEM) to obtain autoradiographs of particles of 239PuO2 deposited in rat lung. The technique was used to obtain quantitative information on the clearance rates of particles from the alveoli, bronchioles and trachea up to 240 d after exposure. At all times, the concentration of particles on the surface of the bronchioles was an order of magnitude greater than on the tracheal surface. The clearance of Pu from both regions followed a biphasic pattern, similar to that obtained by radiometric analysis of the whole lung. Most of the radiation dose to the bronchiolar epithelium originated from Pu particles in peribronchiolar alveoli in which they were preferentially retained, compared to other alveolar regions. The prolonged retention of particles in the peribronchiolar alveoli may be a significant factor in the induction of lung carcinomas. PMID- 2917862 TI - Health implications of radionuclide levels in cattle raised near U mining and milling facilities in Ambrosia Lake, New Mexico. AB - This study was conducted to determine radionuclide tissue levels in cattle raised near U mining and milling facilities. Ambrosia Lake, New Mexico, has been the site of extensive U mining for 30 y and contains several underground U mines, a processing mill, and two large U tailings piles. Ten cows were purchased from two grazing areas in Ambrosia Lake and ten control animals were purchased from Crownpoint, New Mexico. Muscle, liver, kidney, and bone tissue taken from these animals, and environmental samples, including water, grasses and soil collected from the animals' grazing areas, were analyzed for 238U, 234U, 230Th, 226Ra, 210Pb, and 210Po. Mean radionuclide levels in cattle tissue and environmental samples from Ambrosia Lake were higher in almost every comparison than those found in respective controls. Liver and kidney tissues were particularly elevated in 226Ra and 210Po. Radiation dose commitments from eating cattle tissue with these radionuclide concentrations were calculated. We concluded that the health risk to the public from eating exposed cattle is minimal, unless large amounts of this tissue, especially liver and kidney, are ingested. PMID- 2917863 TI - Utilization of femoral head for estimating the skeletal burden of U and Pu in humans. AB - Uranium and Pu were determined in vertebrae, ribs and femoral head samples obtained from the same population. Vertebrae and rib samples were obtained at autopsy and femoral head samples were obtained from persons undergoing hip surgery. The results indicate that there was no statistically (p less than or equal to 0.05) significant difference between the mean concentration of 239,240Pu in vertebrae and ribs. Also, there was no significant difference between the mean concentration of 239,240 Pu in ribs and femoral head. Also, statistical tests were performed to see whether the mean concentrations of 238U and 234U in three different bones differ from each other. The results suggest that there was no statistically significant difference between vertebrae and ribs, vertebrae and head of the femur nor between ribs and femoral head. These results indicate that femoral head may be an appropriate substitute for vertebrae or ribs, the most commonly used bone for inferring the skeletal burden of U and Pu in human. Femoral head samples can be obtained from living persons undergoing hip surgery, while vertebrae and ribs are obtained only at autopsy. PMID- 2917864 TI - Role of the public sector in prevention and management of radiation accidents. PMID- 2917865 TI - Radon-222 levels in low income households. PMID- 2917866 TI - An inexpensive and practical ambient-temperature vacuum still for bioassays. PMID- 2917867 TI - Calibration of a double phoswich detector assembly for estimation of homogeneously or inhomogeneously distributed 241Am and/or 239Pu in untreated fecal samples. PMID- 2917868 TI - Usefulness of water-soluble paper for smear test of low-energy beta- and alpha emitters using a liquid scintillation technique. PMID- 2917869 TI - Health physics activities in the dismantling of a radioactive incinerator. PMID- 2917870 TI - Comment on 'Marble attenuation characteristics for diagnostic x rays'. PMID- 2917871 TI - Reply to Fisher's comment: "Standard for Expression of Powers of 10". PMID- 2917872 TI - A rural health services research agenda. Summary of a conference. December 13-15, 1987, San Diego, California. PMID- 2917874 TI - The changing rural environment and the relationship between health services and rural development. AB - Author summarizes today's changing rural America and the challenges that health services researchers and policymakers face in relating the rural environment to the problems and possibilities of rural health services delivery. PMID- 2917873 TI - Background tables on demographic characteristics, health status, and health services utilization. PMID- 2917875 TI - [Results of treatment of 584 laryngeal cancers at the Ear-Nose-Throat Clinic of Marburg University]. AB - The results in the management of 460 vocal cord carcinomas and 124 supraglottic carcinomas are reported. Of the vocal cord carcinomas, 63.3% were diagnosed in the early Tis and T1 stage. Seventy-six tumors were resected endoscopically, 128 by laryngofissure and chordectomy. Not one of these patients has lost his life, larynx or voice. In bilateral tumors of the T1b category, 2 patients developed local recurrences and lost their larynx. Sixty-two carcinomas of the Tis, T1a and T1b categories were irradiated primarily. Two of these patients died and 14 underwent laryngectomy for local recurrence. In T2 carcinomas a 5-year cure rate of 87.5% was achieved by vertical partial resection. The 5-year cure rate after laryngectomy or laryngectomy with neck dissection for T2N0 and T2N+ carcinoma was 86.2% and 75.0% respectively. Most treatment failures were due to late metastases which could not be controlled. In T3 carcinomas with a 5-year cure rate of 71.4% (N0) and 70.0% (N+) respectively, treatment failures were also mainly seen in patients with N0 necks where we did not carry out a prophylactic neck dissection. Five-year survival rates for primary surgery in supraglottic T1-T4 carcinomas were 100%, 82.4%, 84% and 58.3%. The widely hel opinion that laryngeal carcinoma should only be subjected to surgery for irradiation failure can no longer be sustained. More patients lose their larynx or their life after irradiation of small carcinomas than after primary surgery. Furthermore, too many patients have to undergo two major cancer treatments (irradiation and salvage surgery). In larger carcinomas radiotherapy produces a lower survival rate and too many patients require two stressful cancer therapies. The number of retained larynges is not substantially higher than with primary surgery. Primary irradiation for selected cases should be part of every therapy concept that aims at an adequate and individual treatment of every patient. PMID- 2917876 TI - [Results following total laryngectomy at the Budapest Clinic of Head-Neck surgery]. AB - The data on 356 laryngectomies during a 12-year period were analysed retrospectively. The operations were divided into three groups: group I, laryngectomy alone; group II, laryngectomy and secondary neck dissection; group III, one-stage laryngectomy and radical neck dissection. Most patients had advanced disease (stage III and IV: 54.5% and 23.9%, respectively). Supraglottic and glotto-supraglottic tumours were commonest (39.6% and 36.8%, respectively). The results of palpation, fine-needle biopsy and histology of the lymph nodes are compared. The mean survival time for the three groups was 53.4, 42.7 and 29.8 months, respectively, and the 5-year survival rates were 61.9%, 32.0% and 30.8%, respectively. PMID- 2917877 TI - [Extra-temporal localized facial neuromas]. AB - Nine facial nerve schwannomas were observed in more than 1,350 operations on the parotid gland. Eight patients had a pre-operative diagnosis of pleomorphic adenoma without facial palsy. One patient who underwent extensive surgery without preservation of the facial nerve for a tumour present for more than 10 years had a pre-operative facial palsy. Facial nerve function recovered totally or partially in six peripheral schwannomas. In two cases with main trunk schwannoma no reinnervation was observed despite end-to-end anastomosis or interposition of the great auricular nerve. Histology showed eight typical schwannomas and one neurofibroma. Neurofibromas are extremely rare in the parotid gland. Clinical and operative experience with parotid gland schwannomas shows that recovery of facial nerve defects is mostly incomplete. Reconstructive methods should be used, but the long-term prognosis is uncertain. PMID- 2917878 TI - [Intratemporal course of the facial nerve in magnetic resonance imaging]. AB - MR images of the intratemporal portion of the facial nerve were obtained with a 1.5 Tesla permanent magnet whole-body imaging system. The facial nerve was followed from the internal auditory through the temporal bone to the styloid foramen. MR promises to be a sensitive method for the evaluation of intratemporal facial nerve diseases. PMID- 2917879 TI - [Radiation dosage and clinical value of conventional tomography and high resolution computerized tomography of the nose and ear]. AB - Hypocycloidal (frontal and temporal) tomography of the base of the skull is compared with high resolution computed tomography (HR-CT) with respect to dose and clinical usefulness. In most cases HR-CT is indicated because of its better density resolution in comparison with conventional hypocycloidal tomography. As the X-ray beam is directed at the slice plane the dosage is noticeably less than when using conventional tomography. Slice thickness depends on the required geometric resolution. This is an additional factor in radiation protection. PMID- 2917880 TI - [Frequency-dependent cochlear microphonics in inner ear hearing loss with various pitch thresholds]. AB - Promontory recordings of the cochlear microphonics (CM) after stimulation with 0.5, 1 and 2 kHz tone bursts at 120 dB SPL were performed on normal subjects and patients with various, levels of sensory hearing loss. A significant correlation was found between frequency-related CM amplitudes and the configuration of the pure-tone audiogram. Such recordings provide objective information on hearing abilities at low and middle frequencies and are thus a relevant tool in clinical audiometry. PMID- 2917881 TI - [Increase of phlegmonous forms of infection following angina]. AB - A sudden mini-epidemic of severe septic cervical soft tissue phlegmons following pharyngitis with thrombophlebitis of the jugular veins, mediastinitis and meningeal irritation posed problems of diagnosis and therapy because the typical symptoms were masked by the preceding treatment with antibiotics. The disease could only be partially controlled by intensive care. Three illustrative cases are reported. PMID- 2917882 TI - [Osteochondrosis of the cervical spine as a cause of globus sensation and dysphagia]. AB - Dysphagia and globus hystericus can be caused by disorders of the cervical spine. Functional disorders of the upper cervical spine are the most common cause of dysphagia and globus hystericus due to vertebral disease. Prominent osteophytes of the ventral spine occasionally cause these complaints. In these cases the operative ablation of the osteophytes is effective. This is demonstrated in the following report, and the indication for operation is discussed. PMID- 2917883 TI - Questions conclusion in retrospective study. PMID- 2917885 TI - Do animals have rights? PMID- 2917884 TI - Comments on "Reflections" article. PMID- 2917886 TI - Zoonoses and AIDS in human beings. PMID- 2917887 TI - More on exocrine pancreatic insufficiency. PMID- 2917888 TI - Private enterprise and federal agencies attack sulfamethazine residues. PMID- 2917889 TI - Listening: heart and soul of doctor/client relationships. PMID- 2917890 TI - Use of farrowing rate as a measure of fertility of boars. AB - The first 100 single-boar services of 140 boars were analyzed to determine whether the farrowing rate resulting from initial services predicted the farrowing rate of subsequent services. The data were analyzed for the influence of parity, number of matings per estrus, season of service, and interaction of these variables on farrowing rate. Sow parity influenced farrowing rate. Sows with parity greater than 8 and gilts had the lowest farrowing rates (P less than 0.01). Sows with parity 2 through 5 had the highest farrowing rates (P less than 0.01). One and 2 matings/estrus resulted in reduced farrowing rates (P less than 0.01), compared with farrowing rates of greater than 2 matings/estrus. Farrowing rate for services during the summer was lower than that for other seasons of the year (P less than 0.01). Evidence of interaction among these variables was not found. Therefore, the results of each service recorded was adjusted to the mean farrowing rate of sows with parity 2 through 5, sows mated greater than or equal to 3 times/service, and sows serviced in the spring. After these adjustments, the farrowing rates for the first 10, 20, 30, 40, and 50 services were analyzed to determine associations with farrowing rates for subsequent services through 100 farrowings. These data also were analyzed to determine whether the associations were strengthened by removal of the first 10 services from the data. The best farrowing rate association indicated that for each 1% increase in farrowing rate subsequent to the first 50 services, the farrowing rate for the second 50 services increased 0.33% (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2917891 TI - Radiographic diagnosis of hereditary chondrodysplasia in newborn lambs. AB - Normal appearing Suffolk lambs affected with hereditary chondrodysplasia (HC) and normal appearing unaffected lambs were radiographed at birth, and at 2, 4, and 8 weeks of age. In affected lambs, lesions were seen consistently in the elbows, shoulders, sternum, and spine. Similar lesions were not identified in unaffected lambs. A malformed Corriedale lamb was radiographed to compare its lesions to those seen in HC. The Corriedale lamb had islands of ossification of the anconeal process similar to those identified in lambs with signs of HC at birth. The islands of ossification seen in the Corriedale lamb were fused by 2 months of age, whereas elbow lesions seen in lambs with HC increased in severity during the same period. PMID- 2917892 TI - Keratoconjunctivitis sicca associated with fracture of the stylohyoid bone in a horse. AB - Keratoconjunctivitis sicca developed in a mare with fracture of the stylohyoid bone. Treatment was directed at preserving the health of the globe while local inflammation at the fracture site was resolved. PMID- 2917893 TI - Diagnosis of avian tuberculosis in a horse by use of liver biopsy. AB - A 15-month-old Appaloosa colt had pyrexia, weight loss, diarrhea, and dependent edema. Abnormal laboratory findings included anemia, hypoalbuminemia, and hyperglobulinemia. Activities of liver-specific enzymes in this colt were high. Analysis of a liver biopsy specimen resulted in a presumptive diagnosis of tuberculosis. We recommend that liver biopsy be used as a diagnostic procedure if the differential diagnosis in a horse includes avian tuberculosis or granulomatous enteritis, especially if serum activities of liver-specific enzymes are high. PMID- 2917894 TI - Campylobacteriosis in an aborted equine fetus. AB - Abortion caused by Campylobacter fetus subsp fetus was diagnosed in a 7-month-old equine fetus. The fetus was small for its gestational age. Macroscopically, the proximal portion of the small intestine was hemorrhagic and its wall was thick. Histologically, the Brunner glands were distended with neutrophils, and the submucosa was thick, owing to fluid accumulation and/or cellular infiltrates. Curved bacteria were observed in the Brunner glands and intestinal glands. Campylobacter fetus subsp fetus was isolated from stomach contents, liver, and lungs, and was detected by dark-field microscopic examination of ocular fluid and stomach contents. Placenta was not available for examination. PMID- 2917895 TI - Monorchidism in three colts. AB - Three monorchid colts were admitted for castration as cryptorchids. Two colts each had one normal descended testis, and the third colt had a small testis in the abdomen. Monorchidism was diagnosed at surgery by locating an incomplete epididymis without a testis. After the incomplete epididymis and other testis were removed, the absence of testicular tissue was confirmed by results of a human chorionic gonadotropin response test. PMID- 2917896 TI - Sperm granuloma in a stallion. AB - A 7-year-old stallion with a history of abdominal pain after it fell was examined and found to have a swelling of the right testis and epididymis. Semen evaluation revealed an increase in secondary sperm abnormalities. The stallion was unilaterally castrated. The histologic diagnosis was sperm granuloma, with no evidence of infection. Periductal fibrosis was observed and appeared to have developed before the trauma occurred. The changes seen could be compatible with chronic blockade of efferent ductules, resulting in extravasation of spermatozoa. PMID- 2917897 TI - Treatment of a calf with Clostridium chauvoei infection. AB - In a small beef cattle herd, two 2- to 3-month-old calves had died suddenly. A 2.5-month-old calf, with Clostridium chauvoei infection of the right hip and stifle region, was treated successfully with procaine penicillin G. The herd had not been vaccinated against any disease. PMID- 2917898 TI - Idiopathic gonitis in heifers: 34 cases (1976-1986). AB - Acute suppurative arthritis of the stifle joint was diagnosed in 34 Holstein heifers between 1976 and 1986. Only 1 stifle joint was affected in each heifer; however, 1 heifer also had involvement of the contralateral radiocarpal joint. In each heifer, there was marked lameness and synovitis characterized by an effusion with high synovial fluid nucleated cell counts and total protein concentration. Seventy-four percent (25/34) of the heifers had radiographic evidence of an osteolytic lesion involving the lateral tibial plateau. Bacteriologic cultures of synovial fluid, synovial membrane, and bone yielded no growth. Eighteen of 23 (78%) affected heifers for which follow-up data was obtained became productive herd members after treatment. PMID- 2917899 TI - Trend in real starting salaries of US veterinary medical college graduates, 1980 1988. PMID- 2917900 TI - What is your diagnosis? Lysis of the vertebral body of C7, with a pathologic compression fracture and compression of the spinal cord at the level of C7. PMID- 2917901 TI - More on leishmaniasis in Ohio. PMID- 2917902 TI - Testing for tuberculosis in nonhuman primates. PMID- 2917903 TI - Questions extrauterine development of fetuses. PMID- 2917904 TI - Specialty practice--some legal considerations. PMID- 2917905 TI - ECG of the month. Hyperkalemia in a mare. PMID- 2917906 TI - Efficacy of intrauterine infusion of plasma for treatment of infertility and endometritis in mares. AB - We evaluated the efficacy of intrauterine plasma infusion in mares as a treatment for infertility caused by endometritis and distinguished the effects of intrauterine infusion of plasma vs saline solution. Forty-three subfertile mares were randomly assigned to 1 of 3 treatment groups: untreated controls (n = 14), those treated by saline infusion (n = 14), and those treated by plasma infusion (n = 15). Reproductive status was assessed daily by transrectal ultrasonography. Uterine aspirates and biopsy specimens were obtained 8 days after ovulation for cytologic and histologic evaluation, and mares were treated on days 12 to 16. Uterine aspirates and biopsy specimens were obtained again on day 8 of the next estrous cycle, and the mares were bred at the subsequent estrus. A postovulation intrauterine infusion of either plasma or saline solution was administered to mares in their respective treatment groups. Biopsy specimens were scored from 1 (no indications of inflammation) to 6 (severe inflammation). The pregnancy rate was lower (P less than 0.005) for mares with scores 5 and 6 (0/5) than for those with scores 1 to 4 (17/35). There was no significant effect of treatment nor a treatment by biopsy score interaction on pregnancy rate; however, the pregnancy rate for mares treated with plasma or saline solution (9/27) tended to be lower than for the control (untreated) mares (8/13). There was no change in mean biopsy score between specimens obtained before treatment and those obtained after treatment for the control group and the group treated with saline solution; however, there was a significant increase (P less than 0.05) in scores in the group treated with plasma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2917907 TI - Lameness in a mare with signs of arteriovenous fistula. AB - A 5-year-old mare was evaluated for lameness and swelling of the right forelimb. Clinical findings, including peripheral edema, venous pulsation, palpable thrill in the cephalic vein, disparate arteriovenous oxygen tension differences between the left and right forelimbs, and Branham sign, were suggestive of arteriovenous fistula. Failure to identify the fistula by angiography was attributed to closure of the shunt during anesthesia. Surgical exploration of the affected limb to identify the shunt also was unsuccessful. PMID- 2917908 TI - Serous cystadenoma in a normally cyclic mare with high plasma testosterone values. AB - Serous cystadenoma was diagnosed by histologic examination of a large ovary removed from a 16-year-old Thoroughbred mare with normal estrous cycles. Palpation and ultrasound examination per rectum had revealed an excessive number of follicles in the right ovary. The ovulation fossa was palpable on the right ovary, and the left ovary appeared to have normal activity. Plasma testosterone values were high at the time of examination (0.15 ng/ml), but decreased to normal values (0.09 ng/ml) after removal of the cystadenoma. PMID- 2917910 TI - Hemorrhagic diathesis caused by multiple myeloma in a three-month-old foal. AB - Multiple myeloma was diagnosed in a 3-month-old Quarter Horse foal with chronic weight loss, chronic bronchopneumonia, and epistaxis. The foal had pancytopenia, thrombocytopenia, and monoclonal beta-globulinemia. Bone marrow aspirates contained between 80 and 90% plasma cells. PMID- 2917909 TI - Tourniquet-induced hypertension in a horse. AB - Arterial hypertension developed in a horse anesthetized for arthroscopy and lavage of an inflamed right carpal joint. Anesthesia was induced with xylazine HCl, butorphanol, guaifenesin, and thiamylal Na and was maintained with halothane in oxygen. Arterial hypertension and tachycardia developed within 15 minutes after a pneumatic tourniquet was placed 8 to 10 cm proximal to the right carpus and inflated to 800 mm of Hg. The surgical procedure was expedited, halothane was discontinued and anesthesia was maintained with guaifenesin to facilitate bandaging. Heart rate decreased from 72 to 42 beats/min after the tourniquet cuff was deflated. Mean arterial pressure decreased from 260 mm of Hg to 128 mm of Hg. Differential diagnosis for a rapidly increasing arterial pressure during halothane anesthesia include inadequate plane of anesthesia, signs of pain, hypercapnia, hypoxemia, and/or hyperthermia. PMID- 2917911 TI - Open joint injuries in horses: 58 cases (1980-1986). AB - A retrospective study was made of 58 horses with open joint injuries admitted to the veterinary teaching hospital. Twenty-five (43%) were admitted within 24 hours of injury, 15 (26%) were examined 2 to 7 days after injury, and 18 (31%) were evaluated a week or more after the initial injury. The joints of the lower portions of the limbs most commonly were affected, with injuries that varied from puncture wounds to severe lacerations with soft tissue deficits. Diagnosis was made on the basis of clinical signs and results of synovial fluid analysis and radiography. Radiography was found to be an important diagnostic tool, indicating joint involvement in 80% of horses on which it was done. Sixteen horses were euthanatized on the day of admission; of the horses treated, 53% that were examined within the first 24 hours developed septic arthritis, and the overall survival was 65%. Ninety-two percent of horses examined within 2 to 7 days of injury developed septic arthritis, with 38.5% surviving; all horses evaluated a week or more after joint injury had septic arthritis, and 50% survived. The prognosis for return to function was best in horses that were examined within the first 24 hours. Horses examined more than 24 hours after injury had a significantly (P less than 0.05) higher chance of developing septic arthritis, and thus, were significantly (P less than 0.0014) less likely to survive the injury. PMID- 2917912 TI - What is your diagnosis? Dilatation of the thoracic portion of the esophagus. PMID- 2917913 TI - Oxygen radicals and antioxidant enzymes alter pulmonary vascular reactivity in the rat lung. AB - It has been postulated that changes in the availability of partially reduced O2 species, such as O2 radicals, could serve as a link between PO2 in the alveolus and pulmonary vascular tone (Herz 11: 127-141, 1986). To assess this hypothesis, the hemodynamic effects of acute changes in the balance between the production of O2 radicals and availability of antioxidant enzymes were studied in the isolated perfused rat lung. Intravascular generation of O2 radicals, by administration of xanthine-xanthine oxidase, decreased the pulmonary vascular pressor response to alveolar hypoxia (-55 +/- 5%) and angiotensin II (-58 +/- 10%, P less than 0.01 for each) in isolated perfused rat lungs without increasing the lung wet-to-dry weight ratio. Decreases in pulmonary vascular reactivity were inhibited by pretreatment of the lung with desferrioxamine or a mixture of catalase and superoxide dismutase. Catalase and superoxide dismutase preserved the hypoxic pressor response whether given in liposomes or in dissolved form. Superoxide dismutase administered free in solution, or combined with catalase in liposomes, increased the normoxic pulmonary arterial pressure and enhanced vascular reactivity to angiotensin II and hypoxia. Lungs treated with antioxidant enzymes in liposomes had 50% higher lung catalase levels than control lungs (P less than 0.05). These findings demonstrate that exogenous partially reduced O2 species can decrease pulmonary vascular reactivity and suggest that endogenous radicals, superoxide radical in particular, might be important in modulating pulmonary vascular tone. PMID- 2917914 TI - Relationship of diaphragmatic contractility to diaphragmatic blood flow in newborn lambs. AB - We determined the relationship of diaphragmatic contraction rate to diaphragmatic blood flow (Qdi), metabolism, and contractility in nine open-chested mechanically ventilated newborn lambs. The diaphragm was paced for 15 min at slow (20/min) and fast (100/min) contraction rates each followed by a 30-min rest period. There was a mild reduction in transdiaphragmatic pressure (Pdi) during the slow contraction period accompanied by a shift to the right of the curve relating stimulation frequency (10-100 Hz) to Pdi. Pdi returned to control at the start of the fast contraction period, but then fell by 30% within 2 min with continued fast contraction rates. The frequency-Pdi curve was significantly shifted to the right. Qdi, O2 transport, and O2 consumption increased during slow contraction and to an even greater extent during fast contraction. Fractional O2 extraction reached an apparent maximum during slow contraction. Lactate efflux from the right phrenic vein during slow contraction remained unchanged from control. During fast contraction lactate efflux rose proportionately more than did O2 consumption. We conclude that the energy demands at fast rates of diaphragmatic contraction in newborn lambs cannot be met by aerobic metabolism alone despite increasing O2 transport to the diaphragm. PMID- 2917915 TI - Role of costal and crural diaphragm and parasternal intercostals during coughing in cats. AB - The inspiratory phase of coughs often consists of large inspired volumes and increased motor discharge to the costal diaphragm. Furthermore, diaphragm electrical activity may persist into the early expiratory portion of coughs. To examine the role of other inspiratory muscles during coughing, electromyograms (EMG) recorded from the crural diaphragm (Dcr) and parasternal intercostal (PSIC) muscles were compared to EMG of the costal diaphragm (Dco) in anesthetized cats. Tracheal or laryngeal stimulation typically produced a series of coughs, with variable increases in peak inspiratory EMGs of all three muscles. On average, peak inspiratory EMG of Dco increased to 346 +/- 60% of control (P less than 0.001), Dcr to 514 +/- 82% of control (P less than 0.0002), and PSIC to 574 +/- 61% of control (P less than 0.0005). Augmentations of Dcr and PSIC EMG were both significantly greater than of Dco EMG (P less than 0.05 and P less than 0.002, respectively). In most animals, EMG of Dco correlated significantly with EMG of Dcr and of PSIC during different size coughs. Electrical activity of all three muscles persisted into the expiratory portions of many (but not all) coughs. The duration of expiratory activity lasted on average 0.17 +/- 0.03 s for Dco, 0.25 +/- 0.06 s for Dcr, and 0.31 +/- 0.09 s for PSIC. These results suggest that multiple respiratory muscles are recruited during inspiration of coughs, and that the persistence of electrical activity into expiration of coughs is not unique to the costal diaphragm. PMID- 2917916 TI - Effect of exercise on the development of osteoporosis in adult rats. AB - The role of moderate exercise in the prevention of high-turnover osteoporosis was investigated by the use of an animal model. The effect of chronic training on gravimetric, mineral, physical, and histological parameters of normal bone was also examined. Fifty-six adult female Long-Evans rats were divided into four groups: sedentary (C) and exercising controls (E) and sedentary (O) and exercising osteoporotics (EO). Exercising animals ran 4 h/wk for 1 yr. Two percent NH4Cl added to drinking water induced osteoporosis as shown by significantly lower femoral density and breaking strength and histomorphometrically quantified tibial trabecular bone volume but a normal mineral-to-matrix ratio in the O rats. The development of high-turnover osteoporosis in O rats was confirmed by significantly higher alkaline phosphatase activity (P less than 0.05), urinary hydroxyproline content (P less than 0.01), resorption surfaces (P less than 0.01), and histological parameters of bone formation (P less than 0.01). Exercise prevented all these biochemical, biophysical, and histological abnormalities in the EO group. Exercise had no influence on the density of normal femurs but tended to increase their breaking strength (by 11%) compared with femurs of C rats (P = 0.11). PMID- 2917917 TI - Operation Everest II: muscle energetics during maximal exhaustive exercise. AB - To investigate the metabolic basis for the reduction in peak blood lactate concentration that occurs with maximal exercise after acclimatization to altitude, eight male subjects [maximal O2 uptake of 51.2 +/- 3.0 (SE) ml.kg-1.min 1] were acclimated to progressive hypobaria over a 40-day period. Before decompression (SL-1), at 380 and 282 Torr, and on return to sea level (SL-2) the subjects performed progressive cycle exercise to exhaustion. Analysis of muscle samples obtained from the vastus lateralis before exercise and at exhaustion indicated a pronounced reduction (P less than 0.05) in muscle lactate concentration (mmol/kg dry wt) at 282 Torr (39.2 +/- 11) compared with SL-1 (113 +/- 9.7), 380 Torr (94.6 +/- 18), and SL-2 (92.7 +/- 22). For the other glycolytic intermediates studied (glucose 1-phosphate, glucose 6-phosphate, fructose 6-phosphate, fructose 1,6-bisphosphate, and pyruvate) only the increase in glucose 1-phosphate, glucose 6-phosphate, and fructose 6-phosphate were blunted (P less than 0.05) at 282 Torr. The reduction in muscle glycogen concentration during exercise was similar (P less than 0.05) for all environmental conditions. Although exercise resulted in reductions (P less than 0.05) in ATP and creatine phosphate averaging 30 and 51%, respectively, the magnitude of the change was not dependent on the degree of hypobaria. Inosine monophosphate was elevated (P less than 0.05) approximately 11-fold with exercise at both SL-1 and SL-2. These findings support the hypothesis that the lower lactate concentration observed at 282 Torr after exhaustive exercise is due to a reduction in anaerobic glycolysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2917918 TI - Hemodynamic effects of arginine vasopressin in rats adapted to chronic hypoxia. AB - Acute and chronic pulmonary and systemic hemodynamic responses to arginine vasopressin (AVP) were examined in 4-wk hypoxia-adapted and air control rats. AVP, administered intravenously as bolus injections or sustained infusions, produced major dose-dependent V1-receptor-mediated reductions in mean pulmonary arterial pressure in hypoxia-adapted rats. These effects were comparable in pentobarbital-anesthetized, thoracotomized animals and in conscious, intact rats. Chronic infusions of AVP induced a sustained reduction in mean pulmonary arterial pressure and partially prevented the development of pulmonary hypertension without changing systemic arterial pressure. AVP induced significant decreases in cardiac output in both groups; the cardiac output response was not significantly different in hypoxia-adapted and air control animals. AVP induced almost no change in MPAP in air control rats. Furthermore the systemic pressor effects of AVP were significantly blunted in hypoxia-adapted rats compared with air controls. We conclude that the pulmonary depressor and blunted systemic pressor effects of AVP observed in hypoxia-adapted rats may be related to release of a vasodilator, such as endothelium-derived relaxing factor, vasodilator prostaglandins, or atrial natriuretic peptides. Further study is needed to elucidate these mechanisms and assess the usefulness of AVP and/or its analogues in the treatment and prevention of hypoxia-induced pulmonary hypertension. PMID- 2917919 TI - Bronchial responsiveness and inflammation in guinea pigs exposed to acrolein. AB - Bronchial hyperresponsiveness can be produced experimentally after inhalation of numerous nonimmunospecific stimuli; our objective was to determine whether acrolein, a component of cigarette smoke, could increase bronchial reactivity to intravenously administered acetylcholine in guinea pigs. Bronchial responsiveness was assessed twice before and 1, 2, 6, and 24 h after exposures to less than or equal to 0.01 (sham), 0.31, 0.67, 0.94, or 1.26 parts per million for 2 h (5-7 guinea pigs/group). To examine the possible relationships of responsiveness to inflammatory mediator release and cellular infiltration, bronchoalveolar lavage was performed in another 30 guinea pigs before (control) and 0, 1, 2, 6, or 24 h after exposures. Pulmonary resistance was increased immediately after exposure (5 min) and returned to control values within 30-60 min. Increased bronchial responsiveness was evident within 1 h and became maximal 2-4 h after exposure. The acetylcholine dose necessary to double resistance decreased from 104.2 +/- 7.3 to 79.6 +/- 15.9 at 1 h and was 32.5 +/- 7.9 at 2 h and 32.8 +/- 7.6 micrograms.kg-1 at 6 h. Increases in two eicosanoids, thromboxane B2 (from 167 +/ 21 to 314 +/- 77 pg/ml) and prostaglandin F2 alpha (from 98 +/- 20 to 285 +/- 62 pg/ml) occurred immediately after exposure, whereas an influx of neutrophils occurred 24 h later (from 2.2 +/- 1.2 to 11.3 +/- 3.6%). These temporal relationships suggest that neutrophil infiltration may be a sufficient but not a necessary condition for the onset of bronchial hyperresponsiveness and that injury to cells normally present in the lung are responsible for the mediators thought to influence bronchial responsiveness. PMID- 2917920 TI - Cardiovascular failure and apnea in shock. AB - A model of shock was developed in anesthetized dogs by limiting venous return with a balloon inflated in the right atrium. The change in ventilation (VE) in response to a sustained decrease in arterial pressure (Pa) to 50-60 Torr was studied by recording transdiaphragmatic pressure (Pdi) and diaphragm (Edi) and parasternal intercostal (Eic) electrical activity. Four dogs died of cardiac arrest after 20-60 min. In 11 dogs, VE, after an initial increase, decreased progressively until apnea occurred after 103 +/- 24 min, after 60% reductions in breathing frequency, Pdi, and Eic and a 30% fall in Edi. No decrease in diaphragm contractility was found in response to artificial phrenic nerve stimulation. The cardiocirculatory function deteriorated during shock until it became irreversible at apneic time. No recovery from apnea occurred without a recovery of Pa. We conclude that the fall in VE and ensuing apnea in this model resulted from a decrease in central respiratory neural output associated with a progressive deterioration of the cardiocirculatory function. PMID- 2917921 TI - Determinants of VO2max in rats after high-intensity sprint training. AB - The hemodynamic response to maximal exercise was determined in rats that were subjected to high-intensity sprint training (HIST) and rats that served as sedentary controls. Training consisted of five 1-min bouts of treadmill running at work loads (15% grade, 97 m/min) in excess of the animals' maximal O2 uptake (VO2max) interspersed with 90 s of rest. Training was performed 6 days/wk for 6 wk. After the training regimen, all rats were acutely instrumented with catheters in the right carotid artery and right ventricle. O2 uptakes, hemodynamic parameters, arterial and mixed venous O2 concentrations, blood gases, and acid base status were determined at rest and during submaximal and maximal exercise. Results demonstrated that VO2max of HIST rats was significantly greater than that found for sedentary control rats. This increase in VO2max was due to an increase in maximal cardiac output (Qmax), since maximal arteriovenous O2 difference was similar between trained and sedentary rats. The increase in Qmax was due to an increase in maximal stroke volume (SVmax), because maximal heart rate in trained rats was similar to that in sedentary control rats. Citrate synthase and phosphofructokinase activities measured in the white gastrocnemius, plantaris, and soleus muscles of trained and sedentary rats were similar. These results suggest that the increase in VO2max produced with HIST in rats is strongly linked to an increase in central cardiac function as indicated by an increase in Qmax and SVmax. PMID- 2917922 TI - Distribution of bronchoconstrictor responses in isolated-perfused rat lung. AB - We studied the effects of bronchoconstrictor stimuli administered selectively through isolated-perfused preparations of the bronchial and pulmonary circulations of 80 Sprague-Dawley rats. Dose-related contraction was elicited with infusion of acetylcholine (ACh), histamine, and serotonin (5-HT). Bolus infusion of 10(-5) mol ACh caused a 3.5-fold increase in pulmonary resistance (RL) after infusion into the pulmonary circulation (PC) and a 2.5-fold increase in the bronchial circulation (BC) (P less than 0.05 vs. control) that was blocked selectively in each circulation with atropine. Administration of 10(-5) mol 5-HT into the BC caused only a 45% increase in RL; the same dose of 5-HT caused a 5.1 fold increase in RL in the PC. A biphasic (increase at lower doses/decrease at higher doses) change in RL was elicited by histamine that was converted to dose related constriction after H2-receptor blockade with cimetidine in both BC and PC. Response to exogenous ACh remained viable for greater than 5 h. Infusion of the mast cell degranulating agent, compound 48/80 (48/80), caused increase in RL that corresponded to quantitative recovery of histamine in the perfusates of both BC and PC. Histamine concentration in the perfusate increased from 47.2 +/- 31.8 (base line) to 624 +/- 60.1 ng/ml (2-fold increase in RL) in the BC and from 38.3 +/- 17.7 (base line) to 294.4 +/- 38.1 ng/ml (50% increase in RL) in the PC (P less than 0.001 vs. baseline concentration) after a 0.1-mg/ml dose of 48/80.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2917923 TI - Oxygen delivery rate and sufficiency of oxygenation during ECMO in newborn baboons. AB - Minimum acceptable O2 delivery (DO2) during extracorporeal membrane oxygenation (ECMO) remains to be defined in a newborn primate model. The right atrium, carotid artery, and femoral artery were cannulated, and the ductus arteriosus, aorta, and pulmonary artery ligated in neonatal baboons (Papio cynocephalus) under a combination of ketamine, diazepam, and pancuronium. The internal jugular vein was also cannulated retrograde to the level of the occipital ridge. We measured hemoglobin, pH, arterial and venous PO2 (both from the pump circuit and from the cerebral venous site), serum lactate and bicarbonate concentrations, and pump flow, and we calculated hemoglobin saturations, (DO2), O2 consumption (VO2), systemic O2 extraction, and cerebral O2 extraction. Six baboons were studied during each of two phases of the experiment. In the first, flow rates were varied sequentially from 200 to 50 ml.kg-1.min-1 with saturation maximized. In the second, flow was maintained at 200 ml.kg-1.min-1 and saturation was reduced sequentially from 100 to 38%. VO2 fell significantly below baseline at a flow rate of 50 ml.kg-1.min-1 and a DO2 of 8 +/- 2 (SE) ml.kg-1.min-1 in phase 1 and at DO2 of 12 +/- 5 in phase 2. Both systemic and cerebral O2 extraction rose significantly at a flow of 100 ml.kg-1.min-1 and DO2 of 17 +/- 4 ml.kg-1.min-1 in phase 1, whereas neither rose with decreasing DO2 in phase 2. In fact, cerebral extraction fell significantly DO2 of 16 +/- 6 ml.kg-1.min-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2917924 TI - Ozone-induced changes in pulmonary function and bronchial responsiveness in asthmatics. AB - To compare the responses of asthmatic and normal subjects to high effective doses of ozone, nine asthmatic and nine normal subjects underwent two randomly assigned 2-h exposures to filtered, purified air and 0.4 ppm ozone with alternating 15-min periods of rest and exercise on a cycle ergometer (minute ventilation = 30 l.min 1.m-2). Before and after each exposure, pulmonary function and bronchial responsiveness to methacholine were measured and symptoms were recorded. Ozone exposure was associated with a statistically significant decrease in forced vital capacity (FVC), forced expired volume in 1 s (FEV1), percent FEV1 (FEV1%), and forced expired flow at 25-75% FVC (FEF25-75) in both normal and asthmatic subjects. However, comparing the response of asthmatic and normal subjects to ozone revealed a significantly greater percent decrease in FEV1, FEV1%, and FEF25 75 in the asthmatic subjects. The effect of ozone on FVC and symptom scores did not differ between the two groups. In both normal and asthmatic subjects, exposure to ozone was accompanied by a significant increase in bronchial responsiveness. We conclude that exposure to a high effective ozone dose produces 1) increased bronchial responsiveness in both normal and asthmatic subjects, 2) greater airways obstruction in asthmatic than in normal subjects, and 3) similar symptoms and changes in lung volumes in the two groups. PMID- 2917925 TI - Expiratory neural activities in gasping. AB - The purpose was to characterize expiratory-related neural activities in eupnea and gasping. In decerebrate and vagotomized cats, activities were recorded from the phrenic nerve, spinal intercostal and abdominal nerves, and recurrent laryngeal nerve and its branches. Neural inspiration was defined by phrenic discharge. The spinal and laryngeal nerves discharged in inspiration, expiration, or during both phases. Gasping was induced by freezing the brain stem at the pontomedullary junction, exposure to asphyxia or anoxia, or ligation of the basilar artery and its branches. In gasping, peak phrenic activity typically increased as did inspiratory-related activities of laryngeal and spinal nerves. Expiratory activities were greatly reduced in gasping, with some activities being completely eliminated. Reductions of expiratory activity were more prominent for spinal than laryngeal nerves. Similar results were obtained in cats having intact vagi that were ventilated with a servo-respirator so that lung inflation paralleled phrenic activity. The concept that gasping differs fundamentally form other ventilatory patterns is discussed. PMID- 2917926 TI - Behavioral thermoregulation in mice subjected to high pressure. AB - Mice exposed to normoxic He and Ne at increased pressure and allowed to choose between a neutral and a cool environment showed a preference for the cooler environment. This behavior was apparent at 5.7 but not at 2.5 atm He. At 11.3 atm He and Ne, the behavior was associated with a similar reduction in the deep body temperature to a new steady level. The reduction in body temperature increased with pressure, up to 35 atm He, the maximum studied. Since the heat transfer of the He and Ne gas mixtures is different and both gases exert negligible anesthetic effects, the hydrostatic pressure most likely affects behavioral thermoregulation by affecting neuronal function. PMID- 2917927 TI - Medical collateral ligament healing subsequent to different treatment regimens. AB - The response of transected canine medical collateral ligaments (MCL) to clinical treatment regimens was investigated. These regimens included no surgical repair with no immobilization and surgical repair with various periods of immobilization. The biomechanical, biochemical, and histological properties of the healing MCL were examined 6 and 12 wk postoperatively. At 6 wk, all healing MCLs had increased cellularity with decreased levels of total collagen and increased amounts of reducible Schiff base cross-links and type III collagen. Biomechanically, the varus-valgus (V-V) knee laxity was significantly increased, and no group achieved normal structural or mechanical properties. At 12 wk the histological appearance of the MCL became more normal but still had increased cellularity. Biochemically, the total collagen levels in experimental MCLs were not statistically different from the controls, but these MCLs still had high amounts of type III collagen and an even higher number of reducible cross-links. From knees in which the MCL was not treated, the V-V knee laxity and the ultimate loads of the femur-MCL-tibia complex achieved normal values. However, the stress strain properties for these MCLs and those treated with repair and immobilization did not completely recover. PMID- 2917928 TI - Is resting muscle oxygen uptake controlled by oxygen availability to cells? AB - To estimate oxidative capacity of noncontracting rat skeletal muscle, the isolated gracilis muscle was perfused at various high flow rates with high-PO2 (88 kPa) saline-albumin solution and simultaneously perifused at either low (6.3 kPa) or high PO2 in a calorimeter at 28 degrees C. Under low-PO2 perifusion, specific O2 consumption and heat production rates (MO2 and E, respectively) were flow-rate dependent. E values were all larger than those obtained on blood perfused preparations at 28 degrees C. MO2 reached 0.47 mumol.min-1.g muscle-1 and E reached 4 mW/g. Normalized to 36 degrees C by means of activation energies determined from 30 and 36 degrees C measurements on nonperfused gracilis strips, these maxima correspond to three times the largest MO2 measured by other authors in blood-autoperfused gracilis. Increasing perifusion PO2 from 6.3 to 88 kPa sharply decreased MO2. These results confirm that MO2 of blood-perfused skeletal muscles in vitro (and a fortiori in vivo) is kept much below its maximum for a noncontracting organ; they also suggest that this maximum MO2 is not necessarily an effect of unphysiologically high PO2 in the tissue cells. PMID- 2917930 TI - Transmission of sound generated by sternal percussion. AB - We indirectly determined the transmission path of sound generated by sternal percussion in five healthy subjects. We percussed the sternum of each subject while recording the output audio signal at the posterior left and right upper and lower lung zones. Sound measurements were done during apnea at functional residual capacity, total lung capacity, and residual volume both with the lungs filled with air and with an 80% He-20% O2 (heliox) gas mixture. Three acoustic indexes were calculated from the output sound pulse: the peak-to-peak amplitude, the peak frequency, and the mid-power frequency. We found that the average values of all indexes tended to be greater in the upper than in the ipsilateral lower lung zones. In the upper zones, peak-to-peak amplitude was greater at total lung capacity and residual volume than at functional residual capacity. Replacing air with heliox did not change these results. These experiments, together with others performed during Mueller and Valsalva maneuvers, suggest that resonance of the chest cage is the predominant factor determining the transmission of sternal percussion sounds to the posterior chest wall. The transmission seems to be only minimally affected by the acoustic characteristics of the lung parenchyma. PMID- 2917929 TI - Induction of alveolar epithelial injury by phospholipase A2. AB - Severe damage to the alveolar type I epithelial cell is a characteristic morphological feature of lung injury due to numerous cases. It is postulated that excess phospholipase A2 (PLA2) activity might be responsible for these changes, as one of the naturally occurring products of this enzyme, lysophosphatidylcholine (lysoPC) has been shown to cause selective injury to the type I pneumonocyte when it is instilled into the lower air spaces of the lung. To further investigate this potential mechanism of type I epithelial cell toxicity, we have measured the epithelial permeability-surface area product (PS) for [14C]sucrose as well as whole-lung lysoPC content at several times after instilling PLA2 (Naja naja venom) into either the air spaces or the perfusate of an isolated hamster lung preparation. As a molar percentage of total phospholipids, the normal hamster lung contains approximately 1.5% lysoPC, and this value is not affected by fluid filling of the air spaces or perfusion of the excised lung for periods up to 90 min. When 0.15 U/ml PLA2 is instilled into the air spaces, lung lysoPC content increases to approximately 2.5% and there are barely detectable increases in [14C]sucrose PS. With air space PLA2 concentrations of 0.30 U/ml, lysoPC content increases to between 4 and 5%, [14C]sucrose PS increases by greater than a factor of 10, and flooding of the alveolar spaces occur. Ultrastructural studies of similarly treated lungs show widespread but selective damage to the type I epithelial cells. These same biochemical and functional changes are not seen when the same concentrations of PLA2 are added to the lung perfusate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2917931 TI - Transmission to the chest of sound introduced at the mouth. AB - We examined the transmission to the chest wall of white noise and 25-Hz square wave-generated noise introduced at the mouth of five healthy subjects. The output audio signals were recorded over the left and right upper and lower lung zones, posteriorly. Sound measurements were made during apnea at functional residual capacity, total lung capacity, and residual volume both after breathing air and an 80% He-20% O2 (heliox) gas mixture. We calculated the peak-to-peak amplitude, the peak frequency, and the midpower frequency of the output sound. We found no consistent variations in the values of these indexes due to lung volume or resident gas density. In all cases, the transmitted sound was most intense at the right upper zone. This could not be explained on the basis of technical factors but was probably the result of normal asymmetry of the mediastinal anatomy. These data suggest that sound introduced through the mouth of healthy individuals excites intrathoracic structures but is transmitted through the parenchyma in such a manner that it is not markedly affected by familiar physiological variables. This must be taken into account if objective acoustical tests of lung physiology are to be developed. PMID- 2917932 TI - Immune parameters of untrained or exercise-trained rats after exhaustive exercise. AB - The effect of a single exhaustive swimming exercise bout on immune competence of untrained or exercise-trained female Wistar rats was compared with the competence of control sedentary rats. After the exhaustive exercise bout, the blastogenic response to concanavalin A by spleen cells of untrained rats was extensively suppressed, whereas the response of the trained rats was only marginally suppressed. The suppressed immune competence of the untrained rats after the exhaustive exercise was associated with an increase in immune-suppressive activity of splenic lymphocytes. The macrophages of the untrained rats and of the control sedentary rats were slightly immune suppressive to normal spleen cells through a prostaglandin-dependent mechanism. The addition of prostaglandin E2 (PGE2) to the blastogenesis cultures revealed that the spleen cells of untrained rats were unusually sensitive to the suppressive effects of PGE2. In contrast to the untrained rats, the marginal level of immune suppression in trained rats after the exhaustive exercise was associated with a lesser degree of lymphocyte suppressive activity, an immune stimulatory activity by the splenic macrophages, and an insensitivity of the splenic lymphocytes to the suppressive effects of PGE2. PMID- 2917933 TI - Acoustic rhinometry: evaluation of nasal cavity geometry by acoustic reflection. AB - To study the geometry of the nasal cavity we applied an acoustic method (J. Appl. Physiol. 43: 523-536, 1977) providing an estimate of cross-sectional area as a function of distance. Acoustic areas in a model constructed from a human nasal cast, in the nasal cavity of a cadaver and in 10 normal subjects and two patients with well-defined afflictions of the nasal cavity, were compared with similar areas obtained by computerized tomography (CT) scans, a specially developed water displacement method, and anterior rhinomanometry. We found a coefficient of variation of the areas of less than 2% by the acoustic method compared with 15% for the rhinomanometric measurements. Acoustic areas correlated highly to similar areas obtained by CT scanning (r = 0.94) and by water displacement (r = 0.96). In two patients the acoustic method accurately outlined, respectively, a tumor in the nose and a septum deviation. It is concluded that this method provides an accurate method for measuring the geometry of the nasal cavity. It is easy to perform and is potentially useful for investigation of physiological and pathological changes in the nose. PMID- 2917934 TI - Interaction of inhaled LTC4 with histamine and PGD2 on airway caliber in asthma. AB - To investigate possible mediator interaction in asthma, the effect of inhaled leukotriene (LT) C4 on bronchoconstriction provoked by histamine and prostaglandin (PG) D2 was studied in nine asthmatic subjects. The provocation doses of histamine, PGD2, and LTC4 required to produce a 12.5% decrease in baseline forced expiratory volume in 1 s (FEV1, PD12.5) and to further this fall to 25% (PD25-12.5) were determined. On three subsequent occasions, subjects inhaled either the PD12.5 LTC4 plus vehicle or vehicle plus the PD25-12.5 of either histamine or PGD2, and FEV1 and maximal flow at 70% of vital capacity below total lung capacity after a forced partial expiratory maneuver (Vp30) followed for 45 min. From these results, predicted time-course curves for LTC4 with histamine and LTC4 with PGD2 were calculated. On two final occasions, airway caliber was followed for 45 min after inhalation of the PD12.5 LTC4 followed by the PD25-12.5 of either histamine or PGD2. During the first 9 min after LTC4 histamine and LTC4-PGD2, the decreases in airway caliber were greater than the calculated predicted response. This interaction, although small, was significant with LTC4-PGD2 for both FEV1 (P = 0.01) and Vp30 (P less than 0.05) and with LTC4 histamine for Vp30 (P less than 0.05) but not for FEV1 (P less than 0.05). We conclude that inhaled LTC4 interacts synergistically with histamine and PGD2 and that this effect, although small, may be a relevant interaction in asthma. PMID- 2917935 TI - Exercise alters the distribution of ammonia and lactate in blood. AB - Six subjects (3 males, 3 females) worked for 4 min on a cycle ergometer at 115% of peak O2 uptake (VO2). Venous samples drawn before, directly after, and 15 min after exercise were analyzed for ammonia (NH3) and lactate concentrations of plasma, whole blood, and erythrocytes (RBCs) to examine the effect of exercise on blood NH3 and lactate distribution. Exercise increased (P less than 0.05) the [NH3] of plasma and RBCs, with the larger (P less than 0.05) change in plasma (1.8- vs. 0.7-fold). This reduced (P less than 0.05) the RBC-to-plasma [NH3] ratio of 2.4 at rest to 1.3. The plasma-to-RBC [lactate] gradient (P less than 0.05) at rest (0.5 mmol/l) increased (P less than 0.05) 16-fold immediately after exercise (8.7 mmol/l), reflecting the greater increase (P less than 0.05) in plasma than RBCs [lactate] (15.5 vs. 7.5 mmol/l). [Lactate] and [NH3] did not decrease (P greater than 0.05) immediately after to 15 min after exercise. Plasma and whole blood [NH3] or [lactate] were correlated (r greater than 0.93, P less than 0.01) at all sample times, but the slopes of the relations for [NH3] (immediately after vs. 15 min after exercise) or for [lactate] (before and immediately after vs. 15 min after exercise) differed (P less than 0.05). The results indicate that supramaximal exercise alters the distribution of NH3 and lactate between plasma and RBC, thus changing the relations between plasma and whole-blood concentrations of these metabolites. The alteration of NH3 distribution may reflect changes in the pH gradient between plasma and RBCs. PMID- 2917936 TI - Effect of liver glycogen content on glucose production in running rats. AB - The influence of supranormal compared with normal hepatic glycogen levels on hepatic glucose production (Ra) during exercise was investigated in chronically catheterized rats. Supranormal hepatic glycogen levels were obtained by a 24-h fast-24-h refeeding regimen. During treadmill running for 35 min at a speed of 21 m/min, Ra and plasma glucose increased more (P less than 0.05) and liver glucogen breakdown was larger in fasted-refed compared with control rats, although the stimuli for Ra were higher in control rats, the plasma concentrations of insulin and glucose being lower (P less than 0.05) in control compared with fasted-refed rats. Also, plasma concentrations of glucagon and both catecholamines tended to be higher and muscle glycogenolysis lower in control compared with fasted-refed rats. Lipid metabolism was similar in the two groups. The results indicate that hepatic glycogenolysis during exercise is directly related to hepatic glycogen content. The smaller endocrine glycogenolytic signal in face of higher plasma glucose concentrations in fasted-refed compared with control rats is indicative of metabolic feedback control of glucose mobilization during exercise. However, the higher exercise-induced increase in Ra, plasma glucose, and liver glycogen breakdown in fasted-refed compared with control rats indicates that metabolic feedback mechanisms are not able to accurately match Ra to the metabolic needs of working muscles. PMID- 2917937 TI - Coupling of cardiac and locomotor rhythms. AB - The pressure within exercising skeletal muscle rises and falls rhythmically during normal human locomotion, the peak pressure reaching levels that intermittently impede blood flow to the exercising muscle. Speculating that a reciprocal relationship between the timing of peak intramuscular and pulsatile arterial pressures should optimize blood flow through muscle and minimize cardiac load, we tested the hypothesis that heart rate becomes entrained with walking and running cadence at some locomotion speeds, by means of electrocardiography and an accelerometer to provide signals reflecting heart rate and cadence, respectively. In 18 of 25 subjects, 1:1 coupling of heart and step rates was present at one or more speeds on a motorized treadmill, generally at moderate to high exercise intensities. To determine how exercise specific this phenomenon is, and to refute the competing hypothesis that coupling is due to vertical accelerations of the heart during locomotion, we had 12 other subjects cycle on an electronically braked bicycle ergometer. Coupling was found between heart rate and pedaling frequency in 10 of them. Cardiac-locomotor coupling appears to be a normal physiological phenomenon, and its identification provides a fresh perspective from which to study endurance. PMID- 2917938 TI - Cardiovascular response to cycle exercise during and after pregnancy. AB - Our purpose was to determine if pregnancy alters the cardiovascular response to exercise. Thirty-nine women [29 +/- 4 (SD) yr], performed submaximal and maximal exercise cycle ergometry during pregnancy (antepartum, AP, 26 +/- 3 wk of gestation) and postpartum (PP, 8 +/- 2 wk). Neither maximal O2 uptake (VO2max) nor maximal heart rate (HR) was different AP and PP (VO2 = 1.91 +/- 0.32 and 1.83 +/- 0.31 l/min; HR = 182 +/- 8 and 184 +/- 7 beats/min, P greater than 0.05 for both). Cardiac output (Q, acetylene rebreathing technique) averaged 2.2 to 2.8 l/min higher AP (P less than 0.01) at rest and at each exercise work load. Increases in both HR and stroke volume (SV) contributed to the elevated Q at the lower exercise work loads, whereas an increased SV was primarily responsible for the higher Q at higher levels. The slope of the Q vs. VO2 relationship was not different AP and PP (6.15 +/- 1.32 and 6.18 +/- 1.34 l/min Q/l/min VO2, P greater than 0.05). In contrast, the arteriovenous O2 difference (a-vO2 difference) was lower at each exercise work load AP, suggesting that the higher Q AP was distributed to nonexercising vascular beds. We conclude that Q is greater and a vO2 difference is less at all levels of exercise in pregnant subjects than in the same women postpartum but that the coupling of the increase in Q to the increase in systemic O2 demand (VO2) is not different.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2917939 TI - Prolonged whole-body cold water immersion: fluid and ion shifts. AB - To characterize fluid and ion shifts during prolonged whole-body immersion, 16 divers wearing dry suits completed four whole-body immersions in 5 degrees C water during each of two 5-day air saturation dives at 6.1 msw. One immersion was conducted at 1000 (AM) and one at 2200 (PM) so that diurnal variations could be evaluated. Fifty-four hours separated the immersions, which lasted up to 6 h; 9 days separated each air saturation dive. Blood was collected before and after immersion; urine was collected for 12 h before, during, and after immersion for a total of 24 h. Plasma volume decreased significantly and to the same extent (approximately 17%) during both AM and PM immersions. Urine flow increased by 236.1 +/- 38.7 and 296.3 +/- 52.0%, urinary excretion of Na increased by 290.4 +/ 89.0 and 329.5 +/- 77.0%, K by 245.0 +/- 73.4 and 215.5 +/- 44.6%, Ca by 211.0 +/- 31.4 and 241.1 +/- 50.4%, Mg by 201.4 +/- 45.9 and 165.3 +/- 287%, and Zn by 427.8 +/- 93.7 and 301.9 +/- 75.4% during AM and PM immersions, respectively, compared with preimmersion. Urine flow and K excretion were significantly higher during the AM than PM. In summary, when subjects are immersed in cold water for prolonged periods, combined with a slow rate of body cooling afforded by thermal protection and enforced intermittent exercise, there is diuresis, decreased plasma volume, and increased excretions of Na, K, Ca, Mg, and Zn. PMID- 2917940 TI - Surfactant subtypes in mice: characterization and quantitation. AB - Surfactant obtained by bronchoalveolar lavage of normal adult mice was separated into subtypes by a one-step centrifugation to equilibrium on continuous sucrose gradients. Mouse surfactant resolved in this way exists in three subtypes with similar phospholipid compositions. A "light" subtype of buoyant density 1.027 +/- 0.012 (SD) g/ml comprises 43 +/- 18% of the total alveolar lavage phospholipid, has little surface activity, and consists exclusively of small unilamellar vesicles. A "heavy" subtype of buoyant density 1.055 +/- 0.016 g/ml comprises 48 +/- 11% of the total, is surface active, and consists of small amounts of tubular myelin among large empty vesicles. A third component, called "ultraheavy," comprises 9 +/- 4% of the total alveolar lavage phospholipid, has a density of 1.072 +/- 0.020 g/ml, is surface active, and consists of large aggregates of tubular myelin associated with lamellar bodylike structures. Labeling studies suggested that the ultraheavy material was labeled first and was of the same density as purified lamellar bodies. These results are consistent with the view that, in mice, surfactant is secreted into the alveolar compartment in an ultraheavy form, which evolves into the heavy and light forms. PMID- 2917941 TI - Chest wall impedance partitioned into rib cage and diaphragm-abdominal pathways. AB - We measured chest wall "pathway impedances" (ratios of pressure changes to rates of volume displacement at the surface) with esophageal and gastric balloons and inductance plethysmographic belts around the rib cage and abdomen during forced volume oscillations (5% vital capacity, 0.5-4 Hz) at the mouth of five relaxed, seated subjects. Volume displacements of the total chest wall surface, measured by summing the rib cage and abdominal signals, approximated measurements using volume-displacement, body plethysmography over the entire frequency range. Resistance (R) and elastance (E) of the diaphragm-abdomen pathway were several times greater than those of the rib cage pathway, except at the highest frequencies where diaphragm-abdominal E was small. R and E of the diaphragm abdomen pathway and of the rib cage pathway showed the same frequency dependencies as that of the total chest wall: R decreased markedly as frequency increased, and E (especially in the diaphragm-abdomen) decreased at the highest frequencies. These results suggest that the chest wall can be reasonably modeled, over the frequency range studied, as a system with two major pathways for displacement. Each pathway seems to exhibit behavior that reflects nonlinear, rate-independent dissipation as well as viscoelastic properties. Impedances of these pathways are useful indexes of changes in chest wall mechanical behavior in different situations. PMID- 2917942 TI - Impedance of the chest wall during sustained respiratory muscle contraction. AB - We measured total chest wall impedance (Zw), "pathway impedances" of the rib cage (Zrcpath), and diaphragm-abdomen (Zd-apath), and impedance of the belly wall including abdominal contents (Zbw+) in five subjects during sustained expiratory (change in average pleural pressure [Ppl] from relaxation = 10 and 20 cmH2O) and inspiratory (change in Ppl = -10 and -20 cmH2O) muscle contraction, using forced oscillatory techniques (0.5-4 Hz) we have previously reported for relaxation (J. Appl. Physiol. 66: 350-359, 1989). Chest wall configuration and mean lung volume were kept constant. Zw, Zrcpath, Zd-apath, and Zbw+ all increased greatly at each frequency during expiratory muscle contraction; increases were proportional to effort. Zw, Zrcpath, and Zd-apath increased greatly during inspiratory muscle contraction, but Zbw+ did not. Resistances and elastances calculated from each of the impedances showed the same changes during muscle contraction as the corresponding impedances. Each of the resistances decreased as frequency increased, independent of effort; elastances generally increased with frequency. These frequency dependencies were similar to those measured in relaxed or tetanized isolated muscle during sinusoidal stretching (P.M. Rack, J. Physiol. Lond. 183: 1-14, 1966). We conclude that during respiratory muscle contraction 1) chest wall impedance increases, 2) changes in regional chest wall impedances can be somewhat independent, depending on which muscles contract, and 3) increases in chest wall impedance are due, at least in part, to changes in the passive properties of the muscles themselves. PMID- 2917943 TI - Effect of various doses of cocaine on endurance capacity in rats. AB - To determine the effects of a variety of doses of cocaine on endurance capacity, rats were injected intraperitoneally with either 0.1, 0.5, 2.5, 12.5, or 20 mg/kg body wt 20 min before running to exhaustion at 26 m/min up a 10% grade. Animals given saline ran 116 +/- 9 (SE) min. At doses of 12.5 and 20 mg/kg, cocaine reduced endurance time significantly (34 and 74%, respectively). At rest the drug had no effect on liver or fast-twitch muscle glycogen but significantly reduced (20-40%) soleus glycogen at the two highest doses. However, at exhaustion, the quantity of glycogen depleted in the fast-twitch red and white vastus muscles was similar in all groups despite the reduced run times of the animals receiving a higher dose implying a greater rate of glycogenolysis due to cocaine. Blood lactate in the 20 mg/kg group (9.9 +/- 1.2 mM) at exhaustion was nearly twice that of the saline controls at exhaustion (5.1 +/- 0.6). Before exercise plasma norepinephrine (at doses of 2.5, 12.5 and 20 mg/kg) was higher than saline controls and remained higher (20 mg/kg groups) at exhaustion. We conclude that high doses of cocaine cause rapid muscle glycogen depletion and early fatigue. The mechanism by which cocaine causes these effects is not clear. PMID- 2917944 TI - Extracellular matrix proteoglycan degradation by human alveolar macrophages and neutrophils. AB - Degradation and restructuring of the elastin fiber network of the lung is a pivotal process in the pathogenesis of emphysema. Alveolar macrophages and neutrophils are probably directly involved in elastin degradation, but they may also indirectly influence elastin structure and function by altering other extracellular matrix components such as proteoglycans. In this study the mechanisms of proteoglycan degradation by human alveolar macrophages and neutrophils have been explored. Macrophages appear to utilize plasminogen in solubilizing 35SO4-labeled proteoglycans in extracellular matrix produced by neonatal rat vascular smooth muscle cells. Proteoglycan degradation by macrophages is significantly augmented in the presence of 1% human serum. In contrast, neutrophils apparently utilize intrinsic proteinases to solubilize extracellular matrix proteoglycans, and serum inhibits proteoglycan degradation by these cells. Persistent inflammation in the terminal airways of cigarette smokers may produce proteoglycan degradation and influence elastin fiber architecture where the earliest physiological and anatomic evidence of emphysema appears. PMID- 2917945 TI - Calibration of respiratory inductive plethysmograph during natural breathing. AB - We describe a single-posture method for deriving the proportionality constant (K) between rib cage (RC) and abdominal (AB) amplifiers of the respiratory inductive plethysmograph (RIP). Qualitative diagnostic calibration (QDC) is based on equations of the isovolume maneuver calibration (ISOCAL) and is carried out during a 5-min period of natural breathing without using mouthpiece or mask. In this situation, K approximates the ratio of standard deviations (SD) of the uncalibrated changes of AB-to-RC volume deflections. Validity of calibration was evaluated by 1) analyzing RIP waveforms during an isovolume maneuver and 2) comparing changes of tidal volume (VT) amplitude and functional residual capacity (FRC) level measured by spirometry (SP) with RIP values. Comparisons of VT(RIP) to VT(SP) were also obtained in a variety of postures during natural (uninstructed) preferential RC and AB breathing and with voluntary changes of VT amplitude and FRC level. VT(RIP)-to-VT(SP) comparisons were equal to or closer than published reports for single posture, ISOCAL, multiple- and linear regression procedures. QDC of RIP in supine posture with comparisons to SP in that posture and others showed better accuracy in horizontal than upright postures. PMID- 2917946 TI - Pulmonary vascular responses to surgical chemodenervation and chemical sympathectomy in dogs. AB - We investigated the effects of surgical peripheral chemoreceptor denervation, chemical sympathectomy with 6-hydroxydopamine (6-OHDA), and the peripheral chemoreceptor stimulant almitrine on multipoint pulmonary arterial pressure cardiac index (PAP/Q) plots in 30 pentobarbital sodium-anesthetized dogs ventilated alternatively in hyperoxia [fraction of inspired O2, (FIO2) = 0.4] and hypoxia (FIO2 = 0.1). A hypoxic pulmonary vasoconstriction (HPV), i.e., a hypoxia induced increase in PAP over the entire range of Q studied, from 2 to 5 l.min-1.m 2, was elicited in all the animals. Surgical denervation of the carotid and aortic chemoreceptors in a first group of nine dogs increased PAP at the lowest Q of 2 and 3 l.min-1.min-2 in hyperoxia and increased PAP at all levels of Q in hypoxia, so that HPV was enhanced. Chemical sympathectomy in a second group of eight dogs increased PAP at all levels of Q to a comparable extent in hyperoxia and hypoxia so that HPV remained unchanged. Almitrine (8 micrograms.kg-1.min-1 iv) in a third group of eight dogs increased PAP at all levels of Q in hyperoxia but had no effect on PAP/Q plots in hypoxia, so that HPV was inhibited. Almitrine had these same pulmonary vascular effects when administered to the chemodenervated and the sympathectomized dogs. Sham operation and a 2-h delay in a final group of five dogs had no effect on hyperoxic or hypoxic PAP/Q plots. We conclude that in intact dogs 1) the sympathetic nervous system reduces both hyperoxic and hypoxic pulmonary vascular tone, 2) stimulation of the peripheral chemoreceptors inhibits HPV, and 3) almitrine has direct pulmonary vasoconstricting effects in hyperoxia but not hypoxia. PMID- 2917947 TI - Muscle acidosis during static exercise is associated with calf vasoconstriction. AB - In this study we measured (n = 6) the phosphocreatine-to-inorganic phosphate ratio (PCr/Pi), Pi, and pH with 31P-nuclear magnetic resonance (31P-NMR) in the human forearm during static work at 30% of maximal voluntary contraction (MVC) for 2 min followed immediately by 3 min of circulatory arrest (forearm arterial occlusion). Static exercise, with its central volitional and skeletal muscle metabolic and mechanical afferent components, caused a rise in heart rate (HR, 32%), blood pressure (BP, 29%), and calf vascular resistance (calf R, 30%). During forearm occlusion after static exercise, HR returned to base line, the increase in BP was attenuated by 30%, and calf R remained elevated and unchanged. The percent change in calf R was correlated with forearm cellular pH (R = 0.56, P less than 0.001) but only weakly associated with PCr/Pi (R = 0.33, P less than 0.042). 30% MVC for 1 min followed by arterial occlusion (3 min) reduced PCr/Pi by 65% and pH by 0.16 U (P less than 0.05). Calf R was unchanged. Circulatory arrest alone (20 min) caused no change in either pH or calf R but large changes in PCr/Pi (50% reduction). We conclude that 1) there is an association between forearm cellular acidosis and calf vasconstriction during static forearm exercise and 2) large changes in PCr/Pi without concomitant changes in pH are not associated with changes in calf R. PMID- 2917948 TI - Tumor-promoting phorbol esters inhibit monocyte adherence to endothelial cells. AB - Monocyte adherence to endothelial cells (EC) is an important event in the development of a monocytic inflammatory response, yet the effects of inflammatory mediators on monocyte adherence to EC are not well described. We compared the effects of phorbol esters known to activate protein kinase C, including phorbol myristate acetate (PMA) and phorbol 12,13-dibutyrate (PDA), on monocyte adherence to bovine aortic EC. Human monocytes (purity 90 +/- 1% SE) were isolated by centrifugal elutriation to obtain monocytes not previously exposed to a surface. Kinetic studies revealed that 51Cr-labeled monocyte adherence to EC reached a plateau after a 45-min incubation. Concentrations of PMA between 10 and 1,000 ng/ml significantly decreased monocyte adherence to EC (26 +/- 10 and 35 +/- 8% decrease compared with control, respectively). Concentrations of PDA of 100 and 1,000 ng/ml had a similar inhibitory effect. In contrast, the chemotactic stimulus, zymosan-activated serum, significantly increased monocyte adherence (40 +/- 14% increase compared with control). Thus inflammatory stimuli have different effects on the adhesive interaction of monocytes to EC. This may provide a mechanism to selectively modulate monocyte egress from the circulation into extravascular inflammatory sites. PMID- 2917950 TI - Hypoxanthine-xanthine oxidase-related defect in polypeptide chain initiation by endothelium. AB - After exposure to O2 intermediates generated by the hypoxanthine-xanthine oxidase system (HX-XO), the rate of [3H]phenylalanine incorporation into total proteins in cultured endothelial cells was markedly reduced. This reduction, which was prevented by catalase, could not be explained by 1) changes in amino acid pools, 2) increased rate of degradation of newly synthesized proteins, 3) impaired poly(A)+ RNA synthesis and efficiency, 4) decreased rate of amino acylation. On the other hand, the increase in the monoribosome-to-polyribosome ratio suggested that translation was affected at the level of chain initiation. Further analysis indicated that 40S initiation complex formation was normal, whereas the assembly of 80S initiation complex was inhibited. Results from reconstitution experiments showed that both normal and treated ribosomes could support normal protein synthesis in the presence of normal initiation factors (IFs). In contrast, IFs from HX-XO lysates did not support normal protein synthesis with ribosomes from either source. Thus, the effect of XO treatment on protein synthesis appears to be an initiation defect related to decreased IF activity and/or availability. PMID- 2917949 TI - Cigarette smoke extract increases albumin flux across pulmonary endothelium in vitro. AB - Cigarette smoking causes lung inflammation, and a characteristic of inflammation is an increase in vascular permeability. To determine if cigarette smoke could alter endothelial permeability, we studied flux of radiolabeled albumin across monolayers of porcine pulmonary artery endothelium grown in culture on microporous membranes. Extracts (in either dimethylsulfoxide or phosphate buffered saline) of cigarette smoke in a range estimate of concentrations simulating cigarette smoke exposure to the lungs in vivo caused a dose-dependent increase in albumin flux that was dependent on extracellular divalent cations and associated with polymerization of cellular actin. The effect was reversible, independent of the surface of endothelial cells exposed (either luminal or abluminal), and due primarily to components of the vapor phase of smoke. The effects occurred without evidence of cell damage, but subtle morphological changes were produced by exposure to the smoke extracts. These findings suggest that cigarette smoke can alter permeability of the lung endothelium through effects on cytoskeletal elements. PMID- 2917951 TI - Effect of swim exercise training on human muscle fiber function. AB - This study examined the effect of a typical collegiate swim-training program and an intensified 10-day training period on the peak tension (Po), negative log molar Ca2+ concentration (pCa)-force, and maximal shortening speed (Vmax) of the slow-twitch type I and fast-twitch type II fibers of the deltoid muscle. Over a 10-wk period, the swimmers averaged 4,266 +/- 264 m/day swimming intermittent bouts of front crawl, kicking, or pulling. The training program induced an almost twofold increase in the mitochondrial marker enzyme citrate synthase. Po of the single fibers was not altered by either the training or 10-day intensive training programs, and no significant differences were observed in the Po (kg/cm2) of type I compared with the type II fibers. The type II fiber diameters were significantly larger than the type I fibers (94 +/- 4 vs. 80 +/- 2 microns), and although fiber diameters were unaffected by the training, the 10-day intensive training significantly reduced the type II fiber diameter. The type I fibers from the trained swimmers showed pCa-force curves shifted to the right such that higher free Ca2+ levels were required to elicit a given percent of Po (for values less than 0.5 Po). The activation threshold (pCa) for the onset of tension and the pCa required to elicit one-half maximal tension were not altered by the training in either fiber type. Fiber Vmax (measured by the slack test) was fivefold higher in type II compared with type I fibers (4.85 +/- 0.50 vs. 0.86 +/ 0.04 fiber lengths/s). The exercise-training program significantly increased and decreased the Vmax of the slow and fast fibers, respectively. The 10 days of intensified training produced a further significant decrease in the Vmax of the type II fibers. After a period of detraining, the Vmax of both fiber types returned to the control level. The force-velocity relation was not significantly altered in either fiber type by the swim training; however, the intensified training significantly depressed the velocity of the type II fiber at all loads studied. The Vmax changes with exercise training are likely explained by an exercise-induced expression of fast myosin in slow fibers and slow myosin in fast fibers. PMID- 2917952 TI - Tritiated water as a measure of body water in immature rats growing at different rates. AB - Rats were reared from birth in litters of 4, 10, and 16 to achieve different growth rates. Pups in the litters of 16 had no access to rat chow until days 21 28, when chow was made available to one of the litters to induce catch-up growth. Total body water was estimated by tritiated water (TBWHTO) on days 7, 14, 21, and 28 and then calculated from desiccation (TBWdes). TBWHTO was consistently larger than TBWdes for all groups. Differences were 10.9-16.9% on day 7 and 3.7-6.4% on day 28. On day 28, percent difference was higher in the slower-growing than the faster-growing groups. Nonaqueous hydrogen exchange was determined from tritium activity in the dried carcass. Less than 1% of the injected tritium exchanged with nonaqueous hydrogen during the equilibration period. Thus differences between TBWHTO and TBWdes in the younger animals could not be accounted for by nonaqueous hydrogen exchange but may have resulted from a larger loss of injected tritium, possibly in insensible water. PMID- 2917953 TI - A prototype gas exchange monitor for exercise stress testing aboard NASA Space Station. AB - A monitor was developed to track weightlessness deconditioning aboard the National Aeronautics and Space Administration (NASA) Space Station by measuring the O2 uptake (VO2) and CO2 production (VCO2) and calculating maximum VO2 and anaerobic threshold during an exercise stress test. The system uses two flowmeters in series to achieve a completely automatic flow calibration, and it uses breath-by-breath compensation for sample line transport delay. The accuracy of the system was measured over the range of VO2 and VCO2 from 100 to 800 ml/min by means of simulation. Accuracy was 0.54% for VO2 and 2.9% for VCO2. The system was further evaluated using two laboratory methods, the first method being comparison with a breath-by-breath system. As volunteers performed a maximum effort on a cycle ergometer, the mean difference in readings between the two systems was 17 ml/min for VO2 and 8.0 ml/min for VCO2. The correlation coefficient squared was greater than 0.96 for both. The second laboratory test was to use the system for 2 mo in a Human Performance Laboratory. Readings of maximum VO2 (VO2max) and anaerobic threshold were repeatable and consistent with the individual's activity level. The accuracy and convenience of operation will make this a valuable instrument aboard the Space Station. PMID- 2917954 TI - Effect of testosterone on muscle mass and muscle protein synthesis. AB - We have studied the effect of a pharmacological dose of testosterone enanthate (3 mg.kg-1.wk-1 for 12 wk) on muscle mass and total-body potassium and on whole-body and muscle protein synthesis in normal male subjects. Muscle mass estimated by creatinine excretion increased in all nine subjects (20% mean increase, P less than 0.02); total body potassium mass estimated by 40K counting increased in all subjects (12% mean increase, P less than 0.0001). In four subjects, a primed continuous infusion protocol with L-[1-13C]leucine was used to determine whole body leucine flux and oxidation. Whole-body protein synthesis was estimated from nonoxidative flux. Muscle protein synthesis rate was determined by measuring [13C]leucine incorporation into muscle samples obtained by needle biopsy. Testosterone increased muscle protein synthesis in all subjects (27% mean increase, P less than 0.05). Leucine oxidation decreased slightly (17% mean decrease, P less than 0.01), but whole-body protein synthesis did not change significantly. Muscle morphometry showed no significant increase in muscle fiber diameter. These studies suggest that testosterone increases muscle mass by increasing muscle protein synthesis. PMID- 2917955 TI - Mouth pressure curve on abrupt interruption of airflow during forced expiration. AB - An attempt was made to investigate how the mouth pressure curve represents the process of air flowing into the collapsed segment downstream to the choke point when the airflow is abruptly interrupted at the mouth during forced expiration. Immediately after the interruption of airflow, the mouth pressure suddenly increased (phase 1), followed by a slower rise in pressure (phase 2) within approximately 100 ms until the pressure reached the alveolar pressure. The pleural and alveolar pressures remained constant during this process. The first phase of the abrupt rise represented the pressure induced by the instantaneous interruption of the airflow itself. Analysis of the supramaximal flow (Vsupramax) observed after resumption of the airflow suggested that the choke point remained constant during the second phase of the mouth pressure after interruption of maximal flow (Vmax). From these results, examination of the second phase of the mouth pressure curve may provide useful information about the downstream segment of the airway. PMID- 2917956 TI - Lidocaine pharmacokinetics during water immersion in normal humans. AB - Water immersion produces a marked diuresis, natriuresis, and kaliuresis in association with suppression of the renin-aldosterone system. These effects are mediated primarily by an increase in central blood volume. Consequently, this redistribution and the resultant marked increase in cardiac output is associated with alterations in the circulating levels of several volume regulatory hormones, including plasma renin activity and plasma aldosterone. Although the changes in these blood hormonal levels probably reflect perturbation of hormonal release, it is conceivable that the above-mentioned central hemodynamic modifications result in an altered splanchnic blood flow, thereby modulating hormonal clearances. We assessed the effects of immersion on hepatic blood flow by determining the pharmacokinetics of single doses of lidocaine administered intravenously. Seven normal male subjects were studied during a time-control period and during water immersion to the neck. The clearance of lidocaine was unaltered by immersion, suggesting that the presumed marked central hypervolemia and increased cardiac output was not associated with changes in splanchnic blood flow. PMID- 2917957 TI - Motor unit territories supplied by primary branches of the phrenic nerve. AB - Recent studies have demonstrated that, under certain circumstances, the diaphragm does not contract as a homogeneous unit. These observations suggest that motor units may not be randomly distributed throughout the muscle but confined to localized subvolumes. In the present study, electromyographic (EMG) and glycogen depletion methods were combined to investigate the organization of motor units supplied by the primary branches of the phrenic nerve in the cat. Four primary branches are generally present, one branch to the crus and three branches to the sternocostal region. The gross motor-unit territory of each of the four phrenic primary branches was determined by stimulating each nerve separately, while recording from nine EMG electrodes distributed over the hemidiaphragm. Stimulation of the crural branch evoked activity in the ipsilateral crus, whereas stimulation of each of the remaining branches evoked activity in discrete but overlapping areas of the sternocostal diaphragm. A more precise analysis of the distribution and borders of the motor territories was obtained by mapping regions depleted of muscle glycogen due to stimulation of each primary branch for 90 min. Glycogen depletion results closely matched the EMG findings of a localized distribution of motor units served by single primary branches. Stimulation of the crural branch typically caused depletion of the ipsilateral crus, whereas the sternocostal branches each served a striplike compartment. In the majority of cases, the borders of the sternocostal compartments were relatively abrupt and consisted of a 1- to 2-mm transition zone of depleted and nondepleted fibers. These studies demonstrate that motor unit territories of the primary branches of the phrenic nerve are highly delineated. This compartmentalization provides the central nervous system with the potential for a more precise regional motor control of costal and crural diaphragm than previously suspected. PMID- 2917958 TI - Muscle glycogen availability and temperature regulation in humans. AB - The effects of intramuscular glycogen availability on human temperature regulation were studied in eight seminude subjects immersed in 18 degrees C water for 90 min or until rectal temperature (Tre) decreased to 35.5 degrees C. Each subject was immersed three times over a 3-wk period. Each immersion followed 2.5 days of a specific dietary and/or exercise regimen designed to elicit low (L), normal (N), or high (H) glycogen levels in large skeletal muscle groups. Muscle glycogen concentration was determined in biopsies taken from the vastus lateralis muscle before and after each immersion. Intramuscular glycogen concentration before the immersion was significantly different among the L, N, and H trials (P less than 0.01), averaging 247 +/- 15, 406 +/- 23, and 548 +/- 42 (SE) mmol glucose units.kg dry muscle-1, respectively. The calculated metabolic heat production during the first 30 min of immersion was significantly lower during L compared with N or H (P less than 0.05). The rate at which Tre decreased was more rapid during the L immersion than either N or H (P less than 0.05), and the time during the immersion at which Tre first began to decrease also appeared sooner during L than N or H. The results suggest that low skeletal muscle glycogen levels are associated with more rapid body cooling during water immersion in humans. Higher than normal muscle glycogen levels, however, do not increase cold tolerance. PMID- 2917959 TI - Distribution of pulmonary vascular pressure as a function of perinatal age in lambs. AB - The distribution of pulmonary vascular resistance (PVR) with respect to compliance was determined using vascular occlusion in isolated lungs from lambs at five ages, from 2 wk before birth to 1 mo of age. The major change in PVR occurred in the pressure gradient across the middle compliant region (delta Pm), which dropped sharply at birth, remained low for 2 wk, and increased at 1 mo. Pulmonary vasoreactivity also varied with ages. Lungs at 0-4 days did not respond to hypoxia and responded poorly to prostaglandin F2 alpha (PGF2 alpha). In contrast, lungs at 13-33 days had significant increases in delta Pm and the gradient across relatively indistensible arterial vessels during hypoxia and increases in all gradients with PGF2 alpha. Ventilation of fetal lungs reduced PVR, mainly because of a 50% reduction in delta Pm. Our results demonstrate that the magnitude and distribution of PVR relative to compliance varied as a function of perinatal age and that pulmonary vasoreactivity depended on postnatal age. The major effect of ventilating fetal lungs was on the middle region. PMID- 2917960 TI - Muscle glycogenolysis and H+ concentration during maximal intermittent cycling. AB - The relationships between muscle glycogenolysis, glycolysis, and H+ concentration were examined in eight subjects performing three 30-s bouts of maximal isokinetic cycling at 100 rpm. Bouts were separated by 4 min of rest, and muscle biopsies were obtained before and after bouts 2 and 3. Total work decreased from 20.5 +/- 0.7 kJ in bout 1 to 16.1 +/- 0.7 and 13.2 +/- 0.6 kJ in bouts 2 and 3. Glycogenolysis was 47.2 and 15.1 mmol glucosyl U/kg dry muscle during bouts 2 and 3, respectively. Lower accumulations of pathway intermediates in bout 3 confirmed a reduced glycolytic flux. In bout 3, the work done represented 82% of the work in bout 2, whereas glycogenolysis was only 32% of that in bout 2. Decreases in ATP and phosphocreatine contents were similar in the two bouts. Muscle [H+] increased from 195 +/- 12 to 274 +/- 19 nmol/l during bout 2, recovered to 226 +/ 8 nmol/l before bout 3, and increased to 315 +/- 24 nmol/l during bout 3. Muscle [H+] could not be predicted from lactate content, suggesting that ion fluxes are important in [H+] regulation in this exercise model. Low glycogenolysis in bout 3 may be due to an inhibitory effect of increased [H+] on glycogen phosphorylase activity. Alternately, reduced Ca2+ activation of fast-twitch fibers (including a possible H+ effect) may contribute to the low overall glycogenolysis. Total work in bout 3 is maintained by a greater reliance on slow-twitch fibers and oxidative metabolism. PMID- 2917961 TI - Sympathetic activation is associated with increases in EMG during fatiguing exercise. AB - The purpose of this study was to test the hypothesis that efferent sympathetic neural discharge is coupled with the development of muscle fatigue during voluntary exercise in humans. In 12 healthy subjects (aged 20-34 yr) we measured heart rate (HR), arterial blood pressure (AP), and noncontracting, skeletal muscle sympathetic nerve activity (MSNA) in the leg (peroneal nerve) before (control) and during each of three trials of submaximal (30% of maximum) isometric handgrip exercise performed to exhaustion. In six of the subjects of eletromyographic (EMG) activity of the exercising forearm was also measured. HR and AP increased significantly (P less than 0.05) in the 1st min of exercise in all trials. In contrast, neither MSNA nor EMG activity increased significantly above control during the 1st min of exercise, but both parameters subsequently increased in a progressive and parallel manner (P less than 0.05). The overall correlation coefficient between MSNA and EMG activity (144 observations) was 0.85 (P less than 0.001). With successive trials the magnitudes of the increases in HR, AP, MSNA, and EMG activity were greater at any absolute point in time during exercise. These results indicate that sympathetic activation to noncontracting skeletal muscle is directly related to the development of muscle fatigue (as assessed by the change in EMG) during prolonged isometric exercise in humans. Furthermore, our findings demonstrate that previous fatiguing contractions alter the time course of the sympathetic neural adjustments to exercise. PMID- 2917962 TI - Effect of pentoxiphylline on oxygen transport during hypothermia. AB - At least two investigators have demonstrated a reduction in O2 extraction during induced hypothermia (Cain and Bradley, J. Appl. Physiol. 55: 1713-1717, 1983; Schumacker et al., J. Appl. Physiol. 63: 1246-1252, 1987). We hypothesized that administration of pentoxiphylline (PTX), a theobromine that lowers blood viscosity and has vasodilator effects, would increase O2 extraction during hypothermia. To test this hypothesis, we studied O2 transport in anesthetized, paralyzed, mechanically ventilated beagles exposed to hypoxic hypoxia during either 1) normothermia (38 degrees C), 2) hypothermia (30 degrees C), or 3) hypothermia + PTX (30 degrees C and PTX, 20 mg.kg-1.h-1). Measurements included arterial and mixed venous PO2, hemoglobin concentration and saturation, cardiac output, systemic vascular resistance (SVR), blood viscosity, and O2 consumption (VO2). Critical levels of O2 delivery (DO2, the product of arterial O2 content and cardiac output) were determined by a system of linear regression. Hypothermia significantly decreased base line cardiac output (-35%), DO2 (-37%), and VO2 ( 45%), while increasing SVR and blood viscosity. Addition of PTX increased cardiac output (35%) and VO2 (14%), and returned SVR and blood viscosity to normothermic levels. Hypothermia alone failed to significantly reduce the critical level of DO2, but addition of PTX did [normothermia, 11.4 +/- 4.2 (SD) ml.kg-1.min-1; hypothermia, 9.3 +/- 3.6; hypothermia + PTX, 6.6 +/- 1.3; P less than 0.05, analysis of variance]. The O2 extraction ratio (VO2/DO2) at the critical level of DO2 was decreased during hypothermia alone (normothermia, 0.60 +/- 0.13; hypothermia, 0.42 +/- 0.16; hypothermia + PTX, 0.62 +/- 0.19; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2917963 TI - New perspectives in large bowel cancer. PMID- 2917964 TI - Clinical management of hereditary nonpolyposis colon cancer. High-risk clinics and registries. AB - Early age at onset, multiple primary colon cancers, and other clinical features enable recognition of discrete heritable nonpolyposis colon cancer syndromes, when a pattern involving several close relatives can be demonstrated in specific families. Similar clinical expression can be predicted in as-yet asymptomatic relatives and forms a basis for extraordinary early diagnostic measures, involving frequent endoscopic surveillance starting as early as age 20 to 30 years. When even an early cancer is found, radical measures may be indicated, including total colectomy. The invocation of unusual diagnostic and therapeutic measures is admittedly based on a lack of certainty as to genotypic status and natural history in individual cases; as such, the ongoing zealous search for epithelial and serum markers of risk and early neoplastic change is warranted. Because of the relative infrequency, complexity, and uncertainty surrounding high risk families, referral to registries that deal on a daily basis with such problems is still indicated. PMID- 2917965 TI - The Arc and Mnt repressors. A new class of sequence-specific DNA-binding protein. AB - Genetic, biochemical, and biophysical studies have begun to reveal details of the structures of Arc and Mnt and show that these repressors use residues at their N terminal ends for operator recognition and binding. Some of the DNA contacts made by these residues have been identified, and this information together with NMR studies has permitted the construction of models of the DNA binding region. Although the accuracy of these models remains to be determined, it seems clear that Arc and Mnt are members of a new class of DNA-binding proteins. PMID- 2917966 TI - Cloning and characterization of a cDNA that encodes a 70-kDa novel human thyroid autoantigen. AB - cDNA clones were isolated by screening a human thyroid carcinoma lambda gt11 library with immunoglobulins purified from serum of a patient with autoimmune Graves' disease. One clone (ML8) containing a 1.25-kilobase (kb) insert hybridized with a single 2.0-kb poly(A+) mRNA in human thyroid and lymphocytes but not in human brain, liver, kidney, or muscle. In addition, this probe also hybridized with a single 2.0-kb poly(A+) mRNA from a rat thyroid cell line (FRTL 5). An apparently full length 2,074-base pair (bp) human cDNA was obtained and sequenced. The nucleotide sequence of the 2,074-bp cDNA includes a 5'-noncoding sequence of 17 bp, a 1827-bp open reading frame, and a 222-bp 3'-noncoding sequence. The canonical polyadenylation signal AATAAA is present 18 bp upstream of the poly(A) tail. This cDNA encodes a 69,812-dalton protein with two potential N-linked glycosylation sites and at least one potential membrane spanning domain. Immunoprecipitation of the in vitro translated protein by sera from several patients with Graves' disease argues that the 69,812-dalton protein is an autoantigen. PMID- 2917967 TI - Separation of protein X from the dihydrolipoyl transacetylase component of the mammalian pyruvate dehydrogenase complex and function of protein X. AB - The dihydrolipoyl transacetylase (E2)-protein X-kinase subcomplex was resolved to produce an oligomeric transacetylase that was free of protein X and kinase subunits. We investigated the properties of this transacetylase E2 oligomer and of a form of the subcomplex from which only the lipoyl-bearing domain of protein X (XL) was removed. While retaining other catalytic and binding properties of the native subcomplex, the oligomeric transacetylase and the subcomplex lacking the XL domain had greatly reduced capacities both to support the overall reaction of the complex (upon reconstitution with other components) and to bind the dihydrolipoyl dehydrogenase component. Our results indicate that protein X, in part through its XL domain, contributes to the binding of the dihydrolipoyl dehydrogenase component and to the overall reaction of the complex. PMID- 2917968 TI - Deletion of the carboxyl-terminal portion of the transit peptide affects processing but not import or assembly of the small subunit of ribulose-1,5 bisphosphate carboxylase. AB - Import of the small subunit of ribulose-1,5-biphosphate carboxylase/oxygenase into the chloroplast has been proposed to involve two proteolytic cleavages which convert the 20-kDa precursor (pSSU) into the mature 14-kDa subunit (SSU) via an 18-kDa intermediate. A deletion mutant (PSd48/57) of pSSU which lacks 10 amino acids in a conserved region in the carboxyl-terminal portion of the transit peptide is converted into a series of 16-18-kDa polypeptides in addition to the mature 14-kDa SSU when imported into isolated pea chloroplasts. We examined import and processing of this mutant pSSU to determine whether the 16-18-kDa SSUs undergo further maturation in the chloroplast stroma to yield 14-kDa SSU. The ratio of incorrectly processed to 14-kDa SSU is stable up to 60 min following import. This indicates that processing of PSd48/57 involves a single proteolytic cleavage which occurs during or immediately following transit across the chloroplast envelope. The carboxyl-terminal portion of the transit peptide confers either sequence specificity for the processing protease or provides a three-dimensional structure necessary for consistent cleavage at the mature amino terminus of SSU. Incorrectly processed SSUs were incorporated into the holoenzyme demonstrating that removal of the entire transit sequence is not necessary for assembly of the holoenzyme. PMID- 2917969 TI - Introduction of a metal-dependent regulatory switch into an enzyme. AB - A cysteine has been introduced into the hydrophobic binding pocket of staphylococcal nuclease via oligonucleotide-directed mutagenesis. The L89C mutation does not significantly alter the catalytic activity or specificity of the nuclease yet provides a metal-dependent switch for regulating enzymatic activity. The L89C mutant can be inactivated by addition of mercuric or cupric salts and subsequently reactivated by addition of chelating agents. This work may provide a general strategy for regulating the catalytic activity of other enzymes or the binding affinity of proteins to DNA or other proteins. PMID- 2917970 TI - Organic hydroperoxides at high concentrations cause energization and activation of ATP synthesis in mitochondria. AB - The addition of high concentrations of cumene or tert-butyl hydroperoxide to previously deenergized mitochondria results in the energization of these mitochondria and activation of ATP synthesis. The energization effect was observed in the presence of 0.5-0.7 mM cumene hydroperoxide or 2.0-2.5 mM tert butyl hydroperoxide. This energization of mitochondria and activation of oxidative phosphorylation by organic hydroperoxides required the presence of ADP in the mitochondrial matrix and does not depend upon the method of deenergization of the mitochondria. PMID- 2917971 TI - On the mechanism of action of cytochrome P-450. Spectral intermediates in the reaction with iodosobenzene and its derivatives. AB - Cytochrome P-450 is known to catalyze the following oxygen transfer reaction: RH + PhIO----ROH + PhI where RH represents a variety of hydroxylatable substrates and PhIO a variety of iodosobenzene derivatives that serve as oxygen donors, and neither molecular oxygen nor an external electron donor is required. To determine whether the cytochrome functions in such reactions by a peroxidase-type mechanism, the kinetics of its interaction with a variety of substituted iodosobenzenes and iodobenzene diacetates have been determined by stopped flow spectrophotometry. The reaction of phenobarbital-induced rabbit liver microsomal cytochrome P-450 form 2 with iodosobenzenes or iodobenzene diacetates leads to the reversible formation of three spectral intermediates, termed E, F, and G. Complex E is characterized by a type I difference spectrum, representing the iodosobenzene-dependent partial shift of the low spin hexacoordinate form of the ferric enzyme to the high spin pentacoordinate form, F represents a transient intermediate whose spectrum cannot be determined for kinetic reasons, and G represents a blue-shifted intermediate with an absorption maximum at about 393 nm in the absolute spectrum. The striking and principal feature of these observations is that the spectrum of Complex G does not vary with structural differences in the iodosobenzene derivatives, in contrast to the transient species observed in previous studies in this laboratory in the reaction between cytochrome P-450 form 2 and aromatic peroxy compounds. Complex G exhibits the spectral properties one might anticipate for an iron-oxo intermediate containing only one oxygen atom derived from the starting iodosobenzene. PMID- 2917972 TI - Conformation of adenosine bulge-containing deoxytridecanucleotide duplexes in solution. Extra adenosine stacks into duplex independent of flanking sequence and temperature. AB - Structural features at the extra adenosine bulge sites in DNA duplexes have been elucidated from an NMR analysis of two-dimensional through space and through bond connectivities in the self-complementary d(C-C-G-G-A-A-T-T-C-A-C-G-G) (CAC 13 mer) and d(C-C-G-A-G-A-A-T-T-C-C-G-G) (GAG 13-mer) duplexes in aqueous solution. These studies establish that the extra adenosine stacks into the helix at all temperatures below the onset of the melting transition in solution, and the results are independent of whether the extra adenosine is flanked by cytidines (CAC 13-mer) or guanosines (GAG 13-mer). The NMR parameters establish that the extra adenosine can be accommodated into the helix with the flanking base pairs adopting a wedge-shaped orientation. The resulting perturbation extends out to the C10-G11 phosphodiester backbone adjacent to the bulge segment in both the CAC 13-mer and GAG 13-mer duplexes. PMID- 2917973 TI - A novel cDNA extension procedure. Isolation of chicken fatty acid synthase cDNA clones. AB - We have developed a simple and versatile cDNA extension method using lambda exonuclease-generated single-stranded DNA as a primer. This plasmid-based cDNA extension method can be used to synthesize unidirectional extensions of the existing cDNA clones or subcloned fragments of the untranslated and exon regions of genomic DNA clones. The method is simple to use and involves no addition of linkers or tailing. We have successfully used this method to isolate 4.6 kilobase pairs of chicken fatty acid synthase cDNA clones, starting from the fragment of a genomic clone coding for the untranslated region of the fatty acid synthase mRNA. About 2.8 kilobase pairs of the cDNA coding for the chicken fatty acid synthase has been sequenced. The sequence has an open reading frame coding for 945 amino acids of the fatty acid synthase. In the sequence, we have identified the enoyl reductase, NADPH binding region, a putative beta-ketoacyl reductase region, and the entire sequences of acyl carrier protein and the thioesterase domains. The arrangement of these partial activities in this sequence confirms the arrangement of these activities as determined through partial proteolytic mapping studies. The amino acid sequence of chicken fatty acid synthase deduced from cDNA sequences shows a high degree of homology with the rat fatty acid synthase sequence, suggesting that these multifunctional proteins are conserved evolutionarily. PMID- 2917974 TI - Aging of proteins: immunological detection of a glucose-derived pyrrole formed during maillard reaction in vivo. AB - Recent work from this laboratory revealed that glucose-derived pyrroles can form with model amines under physiological conditions (Niroge, F. G., Sayre, L. M., and Monnier, V. M. (1987) Carbohydr. Res. 167, 211-220). The major extractable product, 5-hydroxymethyl-1-alkylpyrrole-2-carbaldehyde (named by us pyrraline) was labile to acid hydrolysis. To allow its detection in proteins undergoing advanced glycosylation, an enzyme-linked immunosorbent assay was developed. An immunogen consisting of epsilon-caproyl pyrraline (hapten) was linked onto poly-L lysine (114:1) and used to raise polyclonal antibodies in the rabbit. High antibody titers were obtained 16 weeks after immunization. The antibody cross reacted with butyl pyrraline (88%), propyl pyrraline (8%), lysyl pyrraline (2%), and neopentyl pyrraline (1.3%). A time-related increase in pyrraline immunoreactivity was observed in bovine serum albumin incubated with glucose (1000 mM), glycated lysine (50 mM), and 3-deoxyglucosone (50 mM) which reached 25, 300, and 350 pmol/mg, respectively, after 30 days. Mean level of protein pyrraline immunoreactivity were 27.0 +/- 7.2 and 43.3 +/- 11.7 pmol/mg in serum albumin from control and diabetic subjects, respectively (p less than 0.001). The pathobiological relevance of pyrraline may relate to its reported antiproteolytic and mutagenic properties. In addition, glucose-derived pyrroles may play a role in diabetic neuropathy in analogy to pyrroles formed during hexane-induced neuropathy. PMID- 2917975 TI - Intracellular substrates for extracellular signaling. Characterization of a ubiquitous, neuron-enriched phosphoprotein (stathmin). AB - We previously identified (Sobel, A., and Tashjian, A. H., Jr. (1983) J. Biol. Chem. 258, 10312-10324) a group of cytoplasmic proteins whose phosphorylation could be related to the regulation by extracellular effectors of cells as different as pituitary and muscle cells. Among these phosphoproteins, proteins "7" and "8" (Mr approximately 19,000, pI approximately 5.8-6.0), that we now designate P1 and P2, are very abundant in rat brain. Partial purification of these proteins was therefore achieved after 100 degrees C precipitation of a rat brain-soluble fraction and further fractionation of the supernatant by ion exchange chromatography. Several related non-phosphorylated (N1, N2) and phosphorylated (P3) proteins were also identified in the heat-resistant supernatant. Antisera raised against P2 extracted from nitrocellulose blots of semipreparative two-dimensional gels recognized all the proteins N1, N2, P1, P2, and P3, confirming that they belong to the same protein family, and suggesting that they are likely various forms of a single protein core. The same protein could be detected biochemically and immunologically at various concentrations in all the tissues or cell types from diverse mammalian and nonmammalian species tested. Together with our previous data relating its phosphorylation to the regulation of the proliferation, differentiation, and/or the functions of the cells considered, this observation leads us to suggest that it might be an ubiquitous regulatory phosphoprotein playing the role of an intracellular "relay" for extracellular signals, after their binding to specific membrane receptors and the generation of second messengers. We propose to name this protein stathmin, from the greek "stathmos" (relay). PMID- 2917976 TI - Human erythrocyte glycophorin C. Gene structure and rearrangement in genetic variants. AB - We have previously shown that a deletion of approximately 3 kilobases in the unique glycophorin C (GPC) gene, which encodes for the human erythrocyte glycophorins C and D, is associated with the Gerbich (Ge) blood group deficiency (Ge-2,-3 and Ge-2,+3 types) (Le van Kim, C., Colin, Y., Blanchard, D., Dahr, W., London, J. & Cartron, J.P. (1987) Eur. J. Biochem. 165, 571-579). We have now isolated and characterized the structure of the GPC gene from the common Ge+2,+3 donors and from a Ge-2,-3 variant (Ge-2,-3 gene). The GPC gene is organized in four exons distributed over 13.5-kilobase pairs (kbp) DNA and contains two directly repeated domains of 3.4 kbp in length which are likely derived from the recent duplication of a unique ancestral domain. Restriction mapping and sequence analysis indicate that a 3.4-kbp deletion within this gene, arising probably by unequal crossing over between the two repeated domains, is responsible for the formation of the Ge-2,-3 gene. The breakpoints of the deletion are located within introns 2 and 3, and therefore exon 3 is removed. The defective gene is transcribed as a mRNA with a continuous open reading frame extending over 300 nucleotides which is translated into an unusual sialoglycoprotein present on Ge 2,-3 red cells. The primary structure of this new glycoprotein has been deduced from nucleotide sequencing. It is proposed in addition, that another 3.4-kb deletion within the GPC gene eliminates exon 2 only by a similar mechanism and generates a defective gene encoding for the abnormal glycoprotein present on Ge 2,+3 erythrocytes. Interestingly, the same deletion which lead to the rare Ge-2, 3 genetic condition, occurred spontaneously and frequently in the cloned GPC gene during the propagation of the recombinant phages in Escherichia coli. From these observations we suggest that the Ge-2,-3 and Ge-2,+3 genes might represent the two allelic forms of a unique ancestral form of the GPC gene, following successive internal duplication and deletion events. PMID- 2917977 TI - Plasma membranes contain half the phospholipid and 90% of the cholesterol and sphingomyelin in cultured human fibroblasts. AB - The literature suggests that cholesterol and sphingomyelin might be essentially confined to plasma membranes in mammalian cells; however, this premise has thus far escaped a direct test. We explored the issue in three ways. First, we fractionated whole homogenates of cultured human fibroblasts by equilibrium sucrose density gradient centrifugation. We found that the profiles of cholesterol and sphingomyelin were indistinguishable from those of two plasma membrane markers, 5' nucleotidase and [3H]galactose, which was conjugated to the surface of intact cells from an exogenous donor by galactosyltransferase. Second, we determined the relative surface areas of intact cells from their uptake of 1 (4-trimethyl-amino)phenyl-6-phenylhexa-1,3,5-triene, a cationic fluorescent dye which partitions into but does not cross plasma membranes. Relative to human red cell ghosts, the apparent surface area of the fibroblasts was 17,500 microns2/cell while for canine hepatocytes, the value was 11,500 microns2/cell. The relative ratios of cell cholesterol to dye binding (hence, surface area) were quite similar in ghosts, fibroblasts, and liver cells; namely 1.0, 1.12, and 0.67, respectively. Finally, we found that the specific ratios of both cholesterol and sphingomyelin to 5' nucleotidase were only 10% less in gradient purified plasma membranes than in whole homogenates. Similar results were obtained using an entirely different method of purification: two-phase aqueous partition. The cholesterol and sphingomyelin in fractions rich in other membranes was closely proportional to their 5' nucleotidase content, suggesting that the presence of these lipids reflected contamination by plasma membrane fragments. The 5' nucleotidase/phospholipid ratio in the purified plasma membrane fraction was roughly twice that in whole cells. We conclude that the compartment marked by 5' nucleotidase in cultured human fibroblasts contains approximately 90% of the two named lipids and half the cell phospholipid phosphorus. PMID- 2917979 TI - Cholic acid synthesis from 26-hydroxycholesterol and 3-hydroxy-5-cholestenoic acid in the rabbit. AB - Intravenous administration of 26-hydroxycholesterol to the rabbit with a bile fistula yielded cholic acid in proportions (84 and 86%) not significantly different from that derived from cholesterol. By contrast, the naturally occurring C27 bile acid 3 beta-hydroxy-5-cholestenoic acid yielded not more than 8% cholic acid. Thus initial 26-hydroxylation of cholesterol followed by 7-alpha hydroxylation can provide sufficient amounts of cholic acid to be considered a quantitatively significant pathway for bile acid synthesis, and in addition it is the only pathway that can be the source of the circulating levels of C24 and C27 monohydroxy bile acids. PMID- 2917978 TI - Effect of t-butyl-hydroperoxide on bradykinin-stimulated changes in cytosolic calcium in vascular endothelial cells. AB - The effect of oxidant stress on agonist-induced changes in endothelial cell cytosolic free Ca2+ (Ca2+i) was measured using the fluorescent probe, fura-2. Cultured vascular endothelial cells were loaded with fura-2 via the acetoxymethyl ester form, fura-2/AM, before incubation with t-butyl-hydroperoxide (0.4 mM). Bradykinin-stimulated changes in (Ca2+i) were measured in cells exposed to the hydroperoxide for 0, 30, 60, 120, and 180 min. Incubation of cells with the oxidant initially (within 30 min) diminished the peak rise in (Ca2+i) that occurs after stimulation with bradykinin. Experiments conducted with cells in a Ca2+ free buffer indicated that t-butyl-hydroperoxide inhibited bradykinin-stimulated Ca2+ influx from the extracellular space and had little effect on agonist-induced release of Ca2+ from internal stores. At the later incubation periods (greater than 60 min), basal (Ca2+i) progressively rose and the peak response to bradykinin progressively decreased. After 180 min, the cells appeared unable to maintain steady-state with respect to Ca2+ flux. These alterations in Ca2+ homeostasis occurred before detectable changes in the ability of the cells to exclude trypan blue. These results suggest that oxidant stress alters the change in Ca2+i of vascular endothelial cells following stimulation with vasoactive agents. PMID- 2917980 TI - Purification and characterization of an alpha-1,2-mannosidase involved in processing asparagine-linked oligosaccharides. AB - A calcium-dependent alpha-1,2-mannosidase involved in the processing of asparagine-linked oligosaccharides was purified to homogeneity from rabbit liver microsomes. N-terminal amino acid analysis was consistent with the presence of a homogeneous protein. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis, under both reducing and nonreducing conditions, revealed a single protein band with an apparent molecular weight of 52,000. Gel filtration and sedimentation analysis under nondenaturing conditions suggested that the purified enzyme is a monomeric protein. The mannosidase is a glycoprotein based on the presence of protein-linked sugar and specific binding of the enzyme to concanavalin A Sepharose. Purified mannosidase was optimally active between pH 5.0 and 6.0. The enzyme was inactive with p-nitrophenyl-alpha-D-mannopyranoside and was inhibited by deoxymannojirimycin but not by swainsonine. The enzyme was specifically activated by Ca2+, with half-maximal activation occurring at concentrations of 10 microM or less and was inhibited by Mn2+, Co2+, Ba2+, and Zn2+. Calcium ions protected the enzyme against inactivation by p-chloromercuribenzoate. Rabbit liver mannosidase hydrolyzed alpha-1,2-mannosyl-mannose linkages in a variety of substrates including methyl-2-O-alpha-D-mannopyranosyl-alpha-D-mannopyranoside (Schutzbach, J. S. (1987) Anal. Biochem. 167, 279-283), ovalbumin glycopeptide IV, and the high mannose chains of thyroglobulin and phytohemagglutinin-P. Approximately 70% of the alpha-1,2-linked mannosyl units in the oligosaccharides of thyroglobulin were accessible to rabbit liver alpha-mannosidase, whereas most of the alpha-1,2-mannosyl units in phytohemagglutinin were resistant to digestion prior to heat denaturation of the plant lectin. PMID- 2917981 TI - Characterization of Na+-dependent phosphate transport in cardiac sarcolemmal vesicles. AB - Pi uptake by purified bovine cardiac sarcolemmal vesicles was stimulated by an inwardly directed Na+ gradient, but not by such gradients of K+, Rb+, Li+, and choline. When Na+ was present both inside and outside the vesicles, or when Na+ gradient was dissipated by monensin, the Na+-dependent Pi uptake increased with time, reached a peak, and then declined approaching a steady state. The initial rate of Na+-dependent Pi uptake was a saturable function of Pi concentration (Km = 0.5 mM). These findings indicate the existence of a Na+,Pi-cotransporter in the sarcolemma. The Na+-activation curve of the Pi uptake exhibited positive cooperativity, suggesting the requirement for multiple Na+ binding to the functional unit of the carrier. The initial rate of Na+-dependent Pi uptake decreased as extra-vesicular pH increased in the range of 5.5-8.7. The uptake rate increased under conditions that are known or expected to generate an inside negative membrane potential, indicating that Pi uptake is accompanied by the uptake of positive charge. These results suggest the electrogenic cotransports of two Na+ and one H2PO4-. We conclude that this cotransporter catalyzes the secondary active transport of Pi across the cardiac plasma membrane and regulates myocardial energy metabolism. We also suggest that the cotransporter may control intracellular Na+ and thus be involved in the regulation of trans-sarcolemmal Ca2+ movement and cardiac contractility. PMID- 2917982 TI - Hepatic glycogen synthesis from duodenal glucose and alanine. An in situ 13C NMR study. AB - An in situ and in vivo surface coil 13C NMR study was performed to study hepatic glycogen synthesis from [3-13C]alanine and [1-13C]glucose administered by intraduodenal infusion in 18-h fasted male Sprague-Dawley rats. Combined, equimolar amounts of alanine and glucose were given. Hepatic appearance and disappearance of substrate and concurrent glycogen synthesis was followed over 150 min, with 5-min time resolution. Active glycogen synthesis from glucose via the direct (glucose----glycogen) and indirect (glucose----lactate----glycogen) pathways and from alanine via gluconeogenesis was observed. The indirect pathway of glycogen synthesis from [1-13C]glucose accounted for 30% (+/- 6 S.E.) of total glycogen formed from labeled glucose. This estimate does not take into account dilution of label in the hepatic oxaloacetate pool and is, therefore, somewhat uncertain. Hepatic levels of [3-13C]alanine achieved were significantly lower than levels of [1-13C]glucose in the liver, and the period of active glycogen synthesis from [3-13C]alanine was longer than from glucose. However, the overall pseudo-first-order rate constant during the period of active glycogen synthesis from [3-13C]alanine (0.075 min-1 +/- 0.026 S.E.) was almost 3 times that from [1 13C]glucose via the direct pathway (0.025 min-1 +/- 0.005 S.E.). The most likely reason for the small rate constant governing direct glycogen formation from duodenally administered glucose compared to that from duodenally administered alanine is a low level of glucose phosphorylating capacity in the liver. PMID- 2917983 TI - Chiral reactions of acetylcholinesterase probed with enantiomeric methylphosphonothioates. Noncovalent determinants of enzyme chirality. AB - Enantiomeric cycloheptyl- and isopropyl methylphosphonothioates containing uncharged and cationic leaving groups, and 3,3-dimethylbutyl methylphosphonyl thiocholines were synthesized, and their inhibition of acetylcholinesterase from Torpedo examined. Bimolecular inhibition constants spanned 10(1)-10(9) M-1.min-1, equilibrium dissociation constants 10(-3)-10(-7) M, and phosphonylation constants 1-300 min-1. A general but not absolute preference for the SP-enantiomer, in the range 170-4600 for cycloheptyl-, 0.6-150 for isopropyl-, and 30 for 3,3 dimethylbutyl methylphosphonothioates, varied with nature of the alkyl ester ( OR) and thioic leaving groups (-SR') surrounding phosphorus. While the overall bimolecular reaction constant showed no marked dependence on ionic strength of the medium, the microscopic kp and KD for the RP- but not SP-cycloheptyl methylphosphonyl thiocholine underwent marked reduction with decreases in ionic strength. This result unmasks the interplay between occupation of the active center and productivity of that occupation. These studies reveal that chiral reactions with acetylcholinesterase are dependent more on the nature of the groups surrounding the tetrahedral phosphorus than on the absolute configuration about the phosphorus atom and indicate that the active center comprises partially overlapping subsites that can accommodate the -OR and -SR' groups. The presence of neighboring subsites characterized by different steric, electrostatic, and hydrophobic properties permits a multiplicity of binding orientations, independent of chiral configuration, and which account for the large variation in chiral preference seen among organophosphonates containing different substituents. PMID- 2917984 TI - Chiral nature of covalent methylphosphonyl conjugates of acetylcholinesterase. AB - This paper examines the chiral nature of the covalent conjugates formed upon reaction of acetylcholinesterase (AchE) with enantiomeric cycloheptyl, isopropyl, and 3,3-dimethylbutyl methylphosphonyl thiocholines. With the exception of the conjugate formed from reaction of AchE with RP-cycloheptyl methylphosphonyl thiocholine, all enantiomeric conjugates underwent oxime reactivation at rates that were within 2-3-fold of each other. Oxime reactivation was, therefore, independent of both initial configuration about phosphorus and the alkyl phosphonyl ester (-OR) moiety. Aging of the enantiomeric cyclopheptyl and isopropyl methylphosphonyl conjugates occurred exclusively for the conjugate formed from the SP-enantiomer and therefore displayed an absolute dependence on the initial configuration of the methylphosphonyl group. Equilibrium titrations with decidium, a fluorescent bisquaternary competitive inhibitor of AchE, provided an index of aging and enantiomeric configuration of the conjugates independent of enzyme activity. Decidium association with the enantiomeric conjugates (prior to aging) showed no marked dependence on the initial configuration about phosphorus but was measurably dependent on nature of the -OR moiety. These results are interpreted with respect to symmetry and nonrigidity of the organophosphonyl conjugates and are consistent with formation of final methylphosphonyl conjugates that are enantiomerically pure and of opposite configuration. These studies indicate that the active center of AchE comprises at least two kinetically distinct environments separate from the esteratic region but located within 5 A of the nucleophilic serine and differing in dipolar characteristics that promote charge separation and general acid catalysis. PMID- 2917985 TI - Kinetics of pH-dependent fusion between 3T3 fibroblasts expressing influenza hemagglutinin and red blood cells. Measurement by dequenching of fluorescence. AB - Fusion between membranes of 3T3 fibroblasts expressing hemagglutinin (HA) from the Japan strain of influenza virus and human red blood cells (RBC) was measured using an assay for lipid mixing based on the relief of self-quenching (dequenching) of fluorescence of the lipid probe octadecylrhodamine (R18). The probe was incorporated into the membrane of intact RBC at self-quenching concentrations, and the RBCs were bound to the 3T3 cells. Fusion, which allowed movement of R18 into 3T3 cell membranes, was monitored by spectrofluorometry as an increase in fluorescence. Upon lowering the pH below 5.4, the fluorescence increased after a delay of about 30 s at 37 degrees C, and leveled off within 2 min. In control experiments where R18 RBCs bound to 3T3 cells expressing the uncleaved precursor hemagglutinin (HA0) were incubated at 37 degrees C and low pH, no fluorescence increase was observed. This indicated that the R18 dequenching occurred as a result of HA-induced fusion of plasma membranes. Fusion showed a very steep pH dependence with a threshold at pH 5.4 and a maximum at pH 5.0, similar to HA-induced fusion seen previously using cell biological techniques. The fusion rate increased and the delay for the onset of fusion decreased as the temperature was raised above 20 degrees C. Low pH activation of the fusion process at 37 degrees C could be partially arrested by raising the pH after 2-10 s, but not after 15 s, indicating that the irreversible pH-activated conformational change of HA necessary for fusion was complete within about 15 s. Analysis of the data indicates that the pH-induced membrane fusion activity of HA is a highly cooperative event. PMID- 2917986 TI - Determination of the disulfide array in the human defensin HNP-2. A covalently cyclized peptide. AB - HNP-2 is a 29-residue peptide present in human neutrophils and is a member of the defensin family of antimicrobial peptides. All defensins contain an invariant disulfide infrastructure comprised of 6 half-cystine residues. The disulfide structure of HNP-2 was determined using a novel method to identify the cross links involving the amino- and carboxyl-terminal cysteine residues. A derivative of HNP-2 was synthesized by covalent modification of the terminal cysteine residues. This derivative was purified, characterized, and subjected to exhaustive proteolytic digestion. Characterization of purified proteolytic fragments by amino acid analysis and/or sequence analysis identified an oligopeptide containing all 6 cystine residues. This oligopeptide was subjected to a single cycle of Edman degradation to cleave the peptide bond linking 2 adjacent cysteines. Purification and characterization of the Edman reaction products allowed for assignment of the disulfide array in HNP-2, revealing a cystine motif unique to the defensin peptide family. Further, the covalent structure of HNP-2 was found to be cyclic as one disulfide links the amino- and carboxyl-terminal cysteine residues. HNP-2 is the only polypeptide known to possess such a configuration. PMID- 2917987 TI - Channeling of urea cycle intermediates in situ in permeabilized hepatocytes. AB - Preferential use of endogenously generated intermediates by the enzymes of the urea cycle was observed using isolated rat hepatocytes made permeable to low molecular weight compounds with alpha-toxin. The permeabilized cells synthesized [14C]urea from added NH4Cl, [14C]HCO3-, ornithine, and aspartate, using succinate as a respiratory substrate; with all substrates saturating, about 4 nmol of urea were formed per min/mg dry weight of cells. Urea usually accounted for about 40 50% of the total (NH3 + ornithine)-dependent counts, arginine for less than 10%, and citrulline for about 30%. Very tight channeling of arginine between argininosuccinate lyase and arginase was shown by the fact that the addition of a 200-fold excess of unlabeled arginine to the incubations did not decrease the percentage of counts found in urea or increase that found in arginine, even though a substantial amount of the added arginine was hydrolyzed inside the cells. The channeling of argininosuccinate between its synthetase and lyase was demonstrated by similar observations; unlabeled argininosuccinate added in 200 fold excess decreased the percentage of counts in urea by only 25%. Channeling of citrulline from its site of synthesis by ornithine transcarbamylase in the mitochondrial matrix to argininosuccinate synthetase in the cytoplasmic space was also shown. These results strongly suggest that the three "soluble" cytoplasmic enzymes of the urea cycle are grouped around the mitochondria and are spatially organized within the cell in such a way that intermediates can be efficiently transferred between them. PMID- 2917988 TI - Characterization of rabbit lactate dehydrogenase-M and lactate dehydrogenase-H cDNAs. Control of lactate dehydrogenase expression in rabbit muscle. AB - Two cDNA clones were isolated, one corresponding to the mRNA coding for lactate dehydrogenase-M (LDH-M), the other to the mRNA coding for lactate dehydrogenase-H (LDH-H). The cDNA inserts consist of the entire open reading frame for LDH-M and a partial sequence, from amino acid 117 to 332, for LDH-H. Using these two clones as probes we demonstrate that: (a) the abundance of mRNA is muscle-type dependent; (b) the ratio M/H subunit for protein and mRNA is well related in the muscles studied; and (c) the M + H mRNA level is not relative to the total LDH activity. PMID- 2917989 TI - Purification, microheterogeneity, and stability of human lipid transfer protein. AB - A method for the purification of lipid transfer protein (LTP) from human plasma was developed with the aid of succinylated low density lipoprotein-Sepharose affinity column chromatography. The purified LTP exhibited a single main band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. However, upon isoelectric focusing on polyacrylamide gel, the preparations consistently showed nine bands with isoelectric points ranging from 4.6 to 5.4. The treatment of LTP with Clostridium perfringens neuraminidase shifted these multiple bands toward higher pH regions due to the release of sialic acid. Extensive treatment with neuraminidase resulted in the appearance of a major band with the isoelectric point of 5.6. The purified LTP was rapidly inactivated upon incubation at 37 degrees C due to the denaturation at the "air"-water interface. Various factors promoting or preventing this interfacial denaturation were elucidated. When purified LTP was stored at 4 degrees C, plasma neuraminidase co-purified with LTP became activated, resulting in the gradual desialylation of LTP. It seemed that the LTP preparations of apparent homogeneity are associated with a trace amount of an inactive form of plasma neuraminidase. The inclusion of 4 mM 2 mercaptoethanol or 0.2% EDTA in the storage media completely prevented the activation of plasma neuraminidase. These agents, however, did not significantly inhibit the already activated neuraminidase. When LTP was stored at -20 degrees C in very low ionic strength media, such as 0.001% EDTA (pH 7.4) and at high protein concentrations, the loss of the activity was minimal even after prolonged storage. PMID- 2917990 TI - Glucocorticoid-induced lymphocytolysis is not mediated by an induced endonuclease. AB - The mechanism of glucocorticoid-induced internucleosomal DNA cleavage and cytolysis of lymphatic cells is not known. Recent data (Compton, M.M., and Cidlowski, J.A. (1987) J. Biol. Chem. 262, 8288-8292) suggested that in vivo treatment of rat thymocytes with glucocorticoids induces a nucleolytic "lysis gene" product(s) responsible for lymphocytolysis. In this paper, the possibility that lymphocytolysis may result from glucocorticoid-induced nuclease(s) was examined. Using the rat thymocytes as a model system, we have shown by electrophoretic, enzymatic, and amino acid sequence analysis that the putative glucocorticoid-induced nucleases identified recently by Compton and Cidlowski are in fact H1, H1(0), and core histones, and their gross appearance is not the result of new histone protein synthesis, but a result of the release of histone containing nucleosomes during chromatin breakdown. Evidence presented here shows that the putative induced nuclease activity is an artifact of the assay system employed. Because our data do not support induction of a glucocorticoid-induced nuclease(s), we examined the possibility that DNA cleavage might be induced by activation of a constitutive endogenous endonuclease. We have shown that it is possible to produce characteristic internucleosomal DNA cleavage of rat thymocytes, merely by incubating intact nuclei from untreated adrenalectomized rat thymocytes with Ca2+ and Mg2+ for a short period of time. However, in glucocorticoid-sensitive human CEM-C7 lymphocytes activation of internucleosomal DNA cleavage was independent of calcium uptake. We conclude that glucocorticoid induction of internucleosomal DNA fragmentation does not necessarily require expression of a new nuclease(s), but is the result of the activation of a constitutive endogenous endonuclease(s). Also, our data suggest that the mechanism which controls activation of internucleosomal DNA cleavage in rat thymocytes differs from that which operates in CEM-C7 lymphocytes. PMID- 2917991 TI - Deadenylation of alpha 1-acid glycoprotein mRNA in cultured hepatic cells during stimulation by dexamethasone. AB - During acute phase induction in rats, alpha 1-acid glycoprotein (AGP) mRNA is modified by a reduction in poly(A) tail size (Shiels, B.R., Northemann, W., Gehring, M.R., and Fey, G.H. (1987) J. Biol. Chem. 262, 12826-12831). In the studies presented here, we analyzed AGP mRNA induction and poly(A) tail modification in both primary rat hepatocytes and in the rat hepatoma cell line HTC. Poly(A) tail shortening occurred during stimulation by both glucocorticoids and hepatocyte stimulating factor. Induction of AGP by the glucocorticoid dexamethasone resulted in an approximately 50-fold increase in transcription by 4 h, which was followed by an equally rapid decrease. The large mRNA pool that resulted from this early burst of transcription was very stable, having a half life of well over 24 h, and the individual molecules in this pool had an average poly(A) tail length of 200-250 bases. This stable pool of AGP mRNAs was then deadenylated to form a pool with an average tail length of 20-50 bases; the time course of this shortening followed that seen in the liver. Ongoing RNA synthesis, but not ongoing protein synthesis, was required for shortening of the tail. In contrast to the conclusion of Shiels et al. (1987), our data indicate that deadenylation occurs in the cytoplasm rather than the nucleus. Our data also suggest that shortening of AGP mRNA represents a specific example of the general deadenylation seen in earlier studies of total cellular RNA. PMID- 2917992 TI - The platelet-derived growth factor-inducible KC gene encodes a secretory protein related to platelet alpha-granule proteins. AB - A full length cDNA clone of the platelet-derived growth factor-inducible KC gene has been isolated, sequenced, and expressed in COS cells. Both sequence analysis and expression studies indicate that KC encodes a secretory protein. Sequence analysis shows that, furthermore, the protein encoded by KC belongs to a growing superfamily of inducible proteins with a common ancestral linkage to the platelet alpha-granule proteins, platelet factor 4, and connective tissue-activating peptide III. A computer-generated phylogenetic tree documents interrelationships between KC and six additional members of this peptide superfamily. The KC gene is, in all probability, the murine homologue of a human gene termed "gro." By extension, the KC protein is the murine counterpart of the protein encoded by the gro gene. The gro protein corresponds to a factor described as "melanoma growth stimulating activity." PMID- 2917993 TI - Purification and properties of a soluble angiotensin II-binding protein from rabbit liver. AB - An angiotensin II-binding activity has been purified almost 3,000-fold to a nearly homogenous state from the 100,000 x g supernatant fraction of rabbit liver. The responsible protein is apparently monomeric since its molecular weight was estimated to be 75,000 in the native state by glycerol gradient centrifugation and in the reduced, denatured state by gel electrophoresis. The Kd and Bmax values of the purified preparation were 7.2 nM and 15.2 nmol of angiotensin II bound per mg of protein, the latter figure agreeing well with the theoretical value of 13.3. Competition experiments with 125I-angiotensin II and unlabeled peptides revealed that the angiotensin antagonist [Sar1,Ala8]angiotensin II (saralasin) and the agonist [des-Asp1]angiotensin II (angiotensin III) were more tightly bound than angiotensin II, whereas angiotensin I and the carboxyl-terminal hexapeptide were less avidly bound. The cardiac peptide, atrial natriuretic factor, also competed for binding to the purified preparation but was about 15-fold less effective than angiotensin II. Although the binding activity was purified in the absence of detergent, a requirement for detergent in the binding reaction emerged during the isolation procedure. Binding by the purified protein exhibited an almost complete dependence upon the presence of detergent, p-chloromercuriphenylsulfonic acid and EDTA. PMID- 2917994 TI - B----A transitions within a 5 S ribosomal RNA gene are highly sequence-specific. AB - The UV footprinting technique has been used to detect and map, at single nucleotide resolution, the formation of A conformations within a sea urchin 5S ribosomal RNA gene. Increasing amounts of the dehydrating agent, trifluorethanol, were used to induce the B----A transition. Our measurements argue that the B----A transition is highly sequence-specific. Fourteen different sequences within a fragment of DNA bearing the 5 S gene were found to undergo the B----A transition independently of one another. There is a striking relationship between the midpoint of the B----A transition for each stretch of DNA and its (G+C) content. DNA sequences at the boundary between A and B conformations do not appear to be significantly distorted. A (dAdT)8 tract at the 3' end of the 5 S gene undergoes the B----A transition in two cooperative steps suggesting that for some sequences the B----A transition may actually proceed through the formation of a previously unidentified intermediate. Although the sequence specificity of the B----A transition may be exploited by regulatory proteins when they bind DNA, our measurements argue that binding of the Xenopus laevis transcription factor 111A to 5 S genes does not. PMID- 2917995 TI - Factor XIIIa-mediated cross-linking of fibronectin in fibroblast cell layers. Cross-linking of cellular and plasma fibronectin and of amino-terminal fibronectin fragments. AB - Factor XIIIa cross-links plasma fibronectin as it is being assembled into the extracellular matrix of cultured human skin fibroblasts (Barry, E. L. R., and Mosher, D. F. (1988) J. Biol. Chem. 262, 10464-10469). We have further characterized this process. Fibroblasts were metabolically labeled with proline in the presence or absence of ascorbate and Factor XIIIa. Endogenous fibronectin in the extracellular matrix was cross-linked by Factor XIIIa. There was no evidence for cross-linking of collagenous proteins. Fibro-blast cell layers were incubated with iodinated 27-kDa heparin-binding or 70-kDa collagen- and heparin binding amino-terminal fibronectin fragments. Factor XIIa cross-linked the fragments into high molecular weight aggregates. The amounts of cross-linked fragments reaches a steady state after 1 to 2 h, whereas intact fibronectin continues to be cross-linked for 24 h. When fibroblast cell layers were pulsed with iodinated fibronectin or amino-terminal fragments and Factor XIIIa was included in the chase media, the high molecular weight aggregates were formed in a step-wise manner. The smallest cross-linking steps were to high molecular weight extracellular matrix molecules forming approximately 270-, 300-, and 440 kDa complexes for the 27-kDa fragment, 70-kDa fragment, and intact fibronectin, respectively. When iodinated fibronectin was bound to fibroblast cell layers and chased into the matrix pool in the absence of Factor XIIIa, it could also be cross-linked into high molecular weight complexes when Factor XIIIa was added to the media. These results, therefore, indicate that both cellular and plasma fibronectin and amino-terminal fragments are cross-linked specifically by Factor XIIIa, that the cross-linking is probably to other fibronectin molecules rather than to collagenous proteins, and that both assembling and assembled fibronectin are substrates for Factor XIIIa. PMID- 2917996 TI - Mutational analysis of the chicken progesterone receptor. AB - Oligonucleotide-directed site mutagenesis was used to prepare a series of chicken progesterone receptor deletion mutants in an attempt to elucidate structure function relationships of the receptor. These mutants spanned the entire 659 amino acid coding region of the A form of the receptor. The ability of these mutants to bind progesterone was analyzed following in vitro transcription and translation. Results obtained indicate that a large portion of the protein ranging from amino acid 420 to the extreme carboxyl terminus is necessary to maintain the protein in a conformation which is capable of binding hormone. Following transient cotransfection of mutant receptor proteins into CV-1 cells along with a reporter gene containing an authentic GRE/PRE (PRE-TK-CAT), our results indicated that any deletion throughout the entire molecule results in a decrease in transcriptional activation. Most of these decreases result from an inability of the mutant receptor proteins to bind DNA or hormone. However, two areas of the receptor have been identified which are unrelated to either DNA or hormone binding but markedly affect the ability of the receptor to transactivate target genes. PMID- 2917998 TI - Differential down-regulation of protein kinase C isozymes. AB - Types I, II, and III protein kinase C have been shown to be products of, respectively, gamma, beta, and alpha genes of this enzyme family (Huang, F. L., Yoshida, Y., Nakabayashi, H., Knopf, J. L., Young, W. S., III, and Huang, K.-P. (1987) Biochem. Biophys. Res. Commun. 149, 946-952). Incubation of the highly purified rat brain protein kinase C isozymes with trypsin (kinase/trypsin (w/w) = 100) under identical conditions results in a preferential degradation of types I and II enzymes, whereas the type III enzyme was relatively resistant to tryptic proteolysis. Degradation of the type III enzyme by trypsin could be facilitated with the addition of Ca2+, phosphatidylserine, and dioleoylglycerol; none of these components alone was effective. Limited proteolysis of the three protein kinase C isozymes generated distinctive fragments for each isozyme, indicating that each isozyme has different trypsin-sensitive sites. Tryptic digestion of the type III protein kinase C was used as a model to determine the effects of various modulators on protein kinase C degradation. While Ca2+ and phosphatidylserine together were sufficient to convert the type III protein kinase C from a trypsin insensitive to a -sensitive form, addition of dioleoylglycerol greatly reduced the Ca2+ requirement for such a conversion. Among the various phospholipids tested, in the presence of either dioleoylglycerol or phorbol ester, phosphatidylserine, cardiolipin, and phosphatidic acid were the most effective, and phosphatidylcholine and phosphatidylethanolamine were the least effective in supporting the digestion of type III protein kinase. Other acidic phospholipids, such as lysophosphatidylserine and phosphatidylinositol, were also effective in supporting the degradation in the presence of phorbol ester but not in the presence of dioleoylglycerol. The relevance of these proteolytic reactions to physiological responses was assessed with phorbol ester on rat basophilic leukemia RBL-2H3 cells, which contained both types II and III protein kinase C. Immunoblot analysis with the isozyme-specific antibodies revealed that phorbol ester induced a faster degradation of type II than that of type III isozyme in these cells. The results demonstrate that the various protein kinase C isozymes have different susceptibilities to proteolysis in vitro, when tested with trypsin, as well as to endogenous proteases in intact cells. PMID- 2917997 TI - Hepatic lipase in the rat ovary. Ovaries cannot synthesize hepatic lipase but accumulate it from the circulation. AB - Hepatic lipase is proposed to have a role in steroidogenesis through its involvement in the metabolism of high density lipoproteins. We examined the activity, synthesis, distribution, and uptake of this enzyme and assessed the content of its mRNA in luteinized ovaries. We found that during peak steroidogenesis, ovaries of pregnant mare's serum gonadotropin-human chorionic gonadotropin-treated immature rats contained heparin-releasable hepatic lipase like activity which was neutralized in a dose-dependent manner by purified antibodies to hepatic lipase isolated from post-heparin perfusates of rat livers. Quantitative immunoelectron microscopy revealed that ovarian hepatic lipase occurred along endothelial cells and was 3-fold more abundant in blood vessels of corpora lutea than those of stroma. However, hepatic lipase was not synthesized by the ovary since radiolabeled enzyme was not immunoisolated from the medium of dispersed luteinized granulosa cells incubated with [35S]methionine whereas it was present in the medium of control cells (hepatocytes). Similarly, hepatic lipase mRNA was detectable in liver but not ovaries or kidneys by Northern or slot blot analyses or by the polymerase chain reaction. Finally, 125I-labeled hepatic lipase injected into tail veins was quickly cleared from the systemic circulation, accumulating in liver, ovaries, kidneys, and spleen. Subsequent heparin injection caused rapid reappearance of radioactivity in the bloodstream and a marked decline of radiolabel in liver and ovaries but a modest decrease of that in kidneys and none in spleen. Exogenous 125I-bovine serum albumin also accumulated in all four organs but was not displaced from liver or ovaries by subsequent administration of heparin. Taken together, these data suggest that steroidogenically active ovaries possess but do not synthesize hepatic lipase. Instead, hepatic lipase originating elsewhere, presumably in the liver, is accumulated from the circulation at heparin-sensitive sites in ovarian blood vessels. PMID- 2917999 TI - Cloning of developmentally regulated genes from Leishmania major and expression following heat induction. AB - The protozoa Leishmania undergo morphological and biochemical transformation from the promastigote to the amastigote form during their life cycle. To characterize this transformation process, we constructed a cDNA library for the promastigote stage of Leishmania major and used differential cDNA hybridization to identify cDNA sequences expressed at different abundance in promastigotes or amastigotes of L. major. P100/11E is a single copy gene whose 1600-nucleotide mRNA is enriched in promastigotes. P101/10 is a repeated gene whose 3300-nucleotide transcript is enriched in amastigotes. These developmentally regulated genes are not linked in the genome of L. major and are located on separate chromosome bands. The abundance of the P101/10 transcript increases severalfold during the transformation process at 37 degrees C in vitro and is thermally induced within 3 h after transfer of promastigotes from 27 to 37 degrees C. Examination of beta tubulin gene expression showed that the relative abundance of the 3400-nucleotide beta-tubulin RNA is decreased at 37 degrees C in vitro. Our results indicate that the expression of two developmentally regulated genes of L. major is controlled at the level of mRNA abundance and provide direct evidence that thermal induction plays a general role in regulating gene expression in Leishmania. PMID- 2918000 TI - The developmentally regulated P100/11E gene of Leishmania major shows homology to a superfamily of reductase genes. AB - The life cycle transformation of the protozoan parasite Leishmania from promastigote to amastigote is accompanied by changes in the level of expression of a number of proteins whose function may be necessary for parasite survival in the sandfly vector or mammalian host. To genetically characterize these proteins, we have cloned and characterized cDNA sequences that vary in abundance during the life cycle of Leishmania major. One sequence (P100/11E) encodes a poly(A+) RNA whose abundance is markedly elevated in promastigotes of L. major. The DNA sequence of the P100/11E cDNA predicts an acidic polypeptide of Mr = 32,000 which shows 40-46% similarity to the superfamily of reductase proteins including 2,5 diketo-D-gluconic acid reductase, aldose reductase, aldehyde reductase, and rho crystallin. The P100/11E sequence of L. major contains the IPKS motif located at the active site of both aldose and aldehyde reductases. The P100/11H sequence was expressed in Escherichia coli, and the purified polypeptide was used to raise rabbit antisera which detect a protein of Mr = 35,000 in promastigotes of L. major. These results provide direct genetic evidence that L. major expresses a sequence homologous to the reductase superfamily as a developmentally regulated gene product in promastigotes. PMID- 2918001 TI - Compression-plate fixation of acute fractures of the diaphyses of the radius and ulna. AB - A retrospective study was done of eighty-seven patients who had 129 diaphyseal fractures of either the radius or the ulna, or both, and who were treated with fixation using an AO dynamic-compression plate. Open fractures were internally fixed primarily, and both comminuted and open fractures routinely had bone grafting. Ninety-eight per cent of the fractures united, and 92 per cent of the patients achieved an excellent or satisfactory functional result. The rate of infection was 2.3 per cent. Refracture occurred after removal of a 4.5-millimeter dynamic-compression plate in two patients, but there were no refractures after removal of a 3.5-millimeter plate. The 3.5-millimeter-plate system gave excellent results in patients who had a fracture of the forearm, and it minimized the risk of refracture. Our results demonstrated that immediate plate fixation of an open fracture of the forearm, with a low rate of complications, is possible. PMID- 2918002 TI - Comparison of computerized tomography parameters of the cervical spine in normal control subjects and spinal cord-injured patients. AB - The cross-sectional area and the sagittal and transverse diameters of the cervical spinal canal were measured, using high-resolution, thin-section computerized-tomography images, in 100 control subjects and forty-two patients who had a traumatic injury to the spinal cord. No significant differences were found between the control and the spinal cord-injured group with regard to the cross-sectional area of the spinal canal; however, the differences between the two groups were significant with regard to mean sagittal and transverse diameters of the spinal canal. The sagittal diameters of the spinal canal of the control group were significantly larger than those of the spinal cord-injured group. Conversely, the transverse diameters of the spinal canal of the spinal cord injured group were significantly larger than those of the control group. These findings suggest that certain patients may be predisposed to spinal cord injury, given sufficient trauma. It is not the total volume of space in the spinal canal that is the critical factor; rather, it is the shape. An index of shape is the ratio of the sagittal to the transverse diameter. The difference between the two groups, based on the ratio of sagittal to transverse diameter, was highly significant. Because this measure is a ratio, there is no need to evaluate an individual on the basis of measurements of absolute values. PMID- 2918003 TI - Cranial subluxation of the odontoid process in rheumatoid arthritis. AB - In eighteen patients who had long-standing severe rheumatoid polyarthritis, cranial subluxation of the odontoid process was caused by erosion and collapse of both the occipitocervical and the atlantoaxial facet joints. In five of the patients, the subluxation caused impairment of cranial nerves. One patient was tetraparetic. Six patients had a posterior fusion of the spine; of these, three also had laminectomy of the atlas. Operative treatment seemed to arrest the subluxation, but there was appreciable functional improvement in only four of the six patients. During an average of four years of follow-up, in the twelve conservatively treated patients, the cranial subluxation of the odontoid process progressed, on average, from 8.6 to 10.5 millimeters. PMID- 2918004 TI - Variations in the gait of normal children. A graph applicable to the documentation of abnormalities. AB - The goal of much orthopaedic treatment of children is to improve their walking. To document the quantitative characteristics of walking, we devised graphic displays of speed, cadence, stride length, and body height on the basis of 2,416 observations of 324 children walking over a range of speeds. The gait graph is an uncomplicated tool for the clinician to use in the documentation and evaluation of gait in children. It also provides the means to relate the walking abilities of patients to the standards for normal children. PMID- 2918005 TI - Posterior subluxation of the glenohumeral joint. AB - Twenty-four patients who had posterior subluxation of the glenohumeral joint were assigned to one of two groups on the basis of the severity of the symptoms. The sixteen patients in Group I, who had less severe symptoms, were treated with a physical therapy program that was based on exercises to strengthen muscles. The eleven patients in Group II (three of whom had no success with physical therapy when they were originally in Group I) had a posterior capsulorrhaphy, with or without a bone block. According to an over-all rating, Group I had a rate of success of 63 per cent, and Group II had a rate of success of 91 per cent. The patients who had more severe ligamentous laxity were not more likely to fail either of the treatment programs. Although voluntary subluxation may be a subtle but important indicator of underlying emotional difficulties, it appears that, in the patient who is emotionally stable, the ability to voluntarily subluxate the shoulder posteriorly is not associated with a negative prognosis for either non surgical or surgical treatment. Patients who have moderately disabling posterior subluxation of the shoulder should be treated with an intensive program that is designed to strengthen muscles. Patients who have symptoms that are severely disabling or who have had no success with non-operative treatment should be treated with posterior capsulorrhaphy. When the posterior aspect of the glenoid is severely deficient and when the posterior portion of the capsule or the infraspinatus tendon is attenuated, a bone block should augment the reconstruction. PMID- 2918006 TI - Capitellocondylar total elbow replacement. A long-term follow-up study. AB - The results of forty total elbow replacements in which a capitellocondylar prosthesis was implanted in thirty-five patients (five of whom had a bilateral procedure) were reviewed retrospectively. The average length of follow-up was 7.2 years (range, four to twelve years). Pronation, supination, and flexion of the elbow improved considerably, but extension did not change a great deal. The average rating of the elbow, according to the scoring system of Ewald et al., improved from 30 to 88 points, but the functional score, as defined by the American Rheumatism Association, improved in only four patients. Malarticulation or dislocation of the prosthesis occurred in ten patients (29 per cent). In two other patients, a deep infection developed, necessitating removal of the prosthesis. Ten prostheses (ten patients) had radiolucent lines on follow-up radiographs, but these lines were not associated with pain or loosening. Seven patients (seven elbows) had a transient ulnar-nerve palsy. The incidence of this complication was reduced from 30 per cent (five of seventeen patients) to 15 per cent (four of twenty-eight patients) when the lateral Kocher approach to the elbow was adopted. PMID- 2918007 TI - Palmar shelf arthroplasty in the rheumatoid wrist. Results of long-term follow up. AB - Sixty-three palmar-shelf arthroplasties (so-called pseudofusions of the wrist) that had been performed between 1970 and 1978 in forty-nine patients were evaluated. The length of follow-up averaged eighty-three months (minimum, twelve months for the wrists that fused and twenty-four months for those that did not). Preoperatively, all wrists were painful, with 96 per cent being moderately or severely so. Carpal subluxation was present in 79 per cent of the wrists. Postoperatively, pain recurred in 84 per cent of the wrists, but it was less severe (mild in 48 per cent, moderate in 35 per cent, and severe in 2 per cent). Sixty-eight per cent of the wrists fused spontaneously and were no longer painful. Of the twenty wrists (32 per cent) that did not fuse, 70 per cent were mildly or moderately painful. In patients who have rheumatoid arthritis, we found that palmar shelf arthroplasty was followed by a high rate of delayed spontaneous fusion and an unacceptably high rate of recurrent pain, although the pain was less severe. PMID- 2918008 TI - Roentgenographic classifications of hemophilic arthropathy. Comparison of three systems and correlation with clinical parameters. AB - In 105 knees, the roentgenographic classifications of hemophilic arthropathy of Arnold and Hilgartner, of Pettersson et al., and of a new system were compared. The amount of interobserver agreement (between two observers) was good for all three systems and, for all three, there was a good correlation between progressive severity of the lesion and decreasing function of the joint. The system of Pettersson et al. was better than that of Arnold and Hilgartner for grading severe arthropathy, but it was not better than the new, simplified system. The new system is a four-sign, 7-point classification, in contrast to the eight-sign, 13-point system of Pettersson et al. PMID- 2918009 TI - Observations on patellar height after proximal tibial osteotomy. AB - Sixty-six knees (sixty patients) that had had a proximal tibial osteotomy were evaluated to determine if any alteration of the patellar height had occurred as a result of the operation. Eighty-nine per cent of the patellae, as measured by the Insall-Salvati index, and 76.3 per cent, as measured by the Blackburne-Peel index, were observed to be lowered as they appeared on the postoperative lateral radiograph. This was probably due to shortening of the patellar ligament after prolonged immobilization in a cast, interstitial scarring of the patellar ligament, and new-bone formation in the area of insertion of the patellar ligament. There was no correlation between the postoperative height of the patella and the need for subsequent revision to a total knee replacement. PMID- 2918010 TI - Gangrene of the upper extremity in diabetic patients. AB - Twenty-two patients who had diabetes mellitus and had needed an amputation for gangrene in an upper extremity at an average age of fifty-one years were identified and followed. The five patients who were still living at the latest follow-up had been followed for an average of 50.6 months. The other seventeen patients survived for an average of only 20.6 months after the amputation. All of the patients were in poor health; eighteen had needed an amputation in a lower extremity, and sixteen received hemodialysis. The results of amputation in an upper extremity were unsatisfactory; the site of the initial amputation healed in only two of the twenty-two patients. In the remaining twenty patients, a total of sixty-three additional operations were performed on an upper extremity, and five of the twenty patients died before the wound had healed. PMID- 2918011 TI - Bonding behavior of a glass-ceramic containing apatite and wollastonite in segmental replacement of the rabbit tibia under load-bearing conditions. AB - Glass-ceramic implants containing apatite and wollastonite were studied under load-bearing conditions in a segmental replacement model in the tibia of the rabbit. Alumina-ceramic implants were used as a control. A sixteen-millimeter segment of the middle of the shaft of the tibia was resected at a point distal to the junction of the tibia and the fibula. The defect was replaced by a fifteen millimeter-long hollow, cylindrical implant that was fixed by intramedullary nailing using a Kirschner wire. Two groups of eight rabbits each (one group with a glass-ceramic implant and the other with an alumina implant) were killed twelve weeks after implantation. Two similar groups were killed twenty-five weeks after implantation. The segment of the tibia that contained the implant was excised and tension-tested. The load to failure of glass-ceramic implants containing apatite and wollastonite increased with time. The loads to failure of the glass-ceramic and alumina implants at twelve weeks after implantation were 19.8 +/- 7.06 and zero newtons, respectively. The loads to failure of glass-ceramic and alumina implants at twenty-five weeks after implantation were 126.4 +/- 32.54 and 19.6 +/ 13.92 newtons, respectively. No glass-ceramic implants broke. A calcium phosphorus layer at the interface of the glass-ceramic and the bone was observed by scanning electron microscopy and electron-probe microanalysis. There was no interposition of soft tissue between the glass-ceramic and the bone, as observed by Giemsa surface staining. PMID- 2918012 TI - Treatment of hemimelias of the lower extremity. Long-term results. AB - We used contemporary methods, including early surgical intervention (usually amputation) and prosthetic rehabilitation, to treat tibial or fibular hemimelia in thirty-three patients (forty-four limbs); twenty-four patients (twenty-nine limbs) had adequate follow-up, and their cases are reported here. After an average length of follow-up of sixteen years, all except two of the patients had an excellent or a good result. No patient had migration of the heel pad or a slough or infection of the skin, and only one patient needed a second operation. The Brown procedure was done on three limbs (two patients), but it always had to be supplemented by a corrective operation. We concluded that early surgical treatment and prosthetic rehabilitation yield an excellent result, not only for the short term but also for the long term. PMID- 2918013 TI - Congenital longitudinal deficiency of the tibia. AB - Fifty-seven patients (seventy-one limbs) who had congenital longitudinal deficiency of the tibia (tibial hemimelia) were retrospectively categorized according to radiographic type (Types 1 through 4, as described by Jones et al.). At an average follow-up of nine years, fifty-six of fifty-seven patients walked independently. An ablative surgical procedure was performed on sixty-one of the seventy-one lower extremities. According to the classification of Jones et al., fifty-four limbs had a Type-1 (a or b) or Type-2 deficiency. In twenty-two of these extremities, disarticulation of the knee was performed; in twenty-five, a Syme amputation; and in one, a Chopart amputation. The ipsilateral foot was retained in six extremities that had a severe Type-1 or Type-2 deficiency. Medial transfer of the fibula (the Brown procedure) generally yielded less than satisfactory results; in ten of fourteen extremities, one or more additional operations were needed. Seventeen extremities were classified as having a Type-3 or Type-4 deficiency; Syme amputation was done in nine and Chopart amputation, in four. Despite satisfactory reconstruction of the ankle, a Syme amputation was necessary in most extremities that had a Type-4 deficiency because a major leg length discrepancy was projected. In four limbs that had a Type-3 or Type-4 deficiency, the foot was retained. PMID- 2918014 TI - Osteomalacia secondary to osteosarcoma. A case report. PMID- 2918015 TI - Rupture of the peroneus longus tendon. Report of three cases. PMID- 2918016 TI - Thoracic myelopathy caused by cervicothoracic diastematomyelia. A case report. PMID- 2918017 TI - Multiple ruptures of flexor tendons due to hypertrophic change at the distal radio-ulnar joint. A case report. PMID- 2918018 TI - Snapping syndrome caused by the semitendinosus tendon. A case report. PMID- 2918020 TI - Disorders of the sacro-iliac joint in children. PMID- 2918019 TI - Dihydroergotamine/heparin in the prevention of deep-vein thrombosis after total hip replacement. PMID- 2918021 TI - Management of displaced extension-type supracondylar fractures of the humerus in children. PMID- 2918022 TI - Low cytoplasmic pH inhibits endocytosis and transport from the trans-Golgi network to the cell surface. AB - A fibroblast mutant cell line lacking the Na+/H+ antiporter was used to study the influence of low cytoplasmic pH on membrane transport in the endocytic and exocytic pathways. After being loaded with protons, the mutant cells were acidified at pH 6.2 to 6.8 for 20 min while the parent cells regulated their pH within 1 min. Cytoplasmic acidification did not affect the level of intracellular ATP or the number of clathrin-coated pits at the cell surface. However, cytosolic acidification below pH 6.8 blocked the uptake of two fluid phase markers, Lucifer Yellow and horseradish peroxidase, as well as the internalization and the recycling of transferrin. When the cytoplasmic pH was reversed to physiological values, both fluid phase endocytosis and receptor-mediated endocytosis resumed with identical kinetics. Low cytoplasmic pH also inhibited the rate of intracellular transport from the Golgi complex to the plasma membrane. This was shown in cells infected by the temperature-sensitive mutant ts 045 of the vesicular stomatitis virus (VSV) using as a marker of transport the mutated viral membrane glycoprotein (VSV-G protein). The VSV-G protein was accumulated in the trans-Golgi network (TGN) by an incubation at 19.5 degrees C and was transported to the cell surface upon shifting the temperature to 31 degrees C. This transport was arrested in acidified cells maintained at low cytosolic pH and resumed during the recovery phase of the cytosolic pH. Electron microscopy performed on epon and cryo-sections of mutant cells acidified below pH 6.8 showed that the VSV-G protein was present in the TGN. These results indicate that acidification of the cytosol to a pH less than 6.8 inhibits reversibly membrane transport in both endocytic and exocytic pathways. In all likelihood, the clathrin and nonclathrin coated vesicles that are involved in endo- and exocytosis cannot pinch off from the cell surface or from the TGN below this critical value of internal pH. PMID- 2918023 TI - Reassociation of microvillar core proteins: making a microvillar core in vitro. AB - Intestinal epithelia have a brush border membrane of numerous microvilli each comprised of a cross-linked core bundle of 15-20 actin filaments attached to the surrounding membrane by lateral cross-bridges; the cross-bridges are tilted with respect to the core bundle. Isolated microvillar cores contain actin (42 kD) and three other major proteins: fimbrin (68 kD), villin (95 kD), and the 110K calmodulin complex. The addition of ATP to detergent-treated isolated microvillar cores has previously been shown to result in loss of the lateral cross-bridges and a corresponding decrease in the amount of the 110-kD polypeptide and calmodulin associated with the core bundle. This provided the first evidence to suggest that these lateral cross-bridges to the membrane are comprised at least in part by a 110-kD polypeptide complexed with calmodulin. We now demonstrate that purified 110K-calmodulin complex can be readded to ATP-treated, stripped microvillar cores. The resulting bundles display the same helical and periodic arrangement of lateral bridges as is found in vivo. In reconstitution experiments, actin filaments incubated in EGTA with purified fimbrin and villin form smooth-sided bundles containing an apparently random number of filaments. Upon addition of 110K-calmodulin complex, the bundles, as viewed by electron microscopy of negatively stained images, display along their entire length helically arranged projections with the same 33-nm repeat of the lateral cross bridges found on microvilli in vivo; these bridges likewise tilt relative to the bundle. Thus, reconstitution of actin filaments with fimbrin, villin, and the 110K-calmodulin complex results in structures remarkably similar to native microvillar cores. These data provide direct proof that the 110K-calmodulin is the cross-bridge protein and indicate that actin filaments bundled by fimbrin and villin are of uniform polarity and lie in register. The arrangement of the cross bridge arms on the bundle is determined by the structure of the core filaments as fixed by fimbrin and villin; a contribution from the membrane is not required. PMID- 2918025 TI - Isolation and characterization of protein kinase C from Y-1 adrenal cell cytoskeleton. AB - The cytoskeletons of Y-1 mouse adrenal tumor cells contain a calcium and phospholipid-dependent protein kinase (protein kinase C) that is bound sufficiently tight to resist extraction by 0.5% Triton but not by 1.0% Triton. The enzyme has been purified to near homogeneity from cytoskeleton and cytosol. It shows features typical of this type of kinase, namely a requirement for Ca2+ and phospholipid, stimulation by tumor promoters but not by nontumor-promoting phorbol esters, and inhibition by trifluoperazine. The enzyme shows specificity for four substrates found in the cytoskeleton, namely 80, 33, 20, and 18 kD. The first three substrates are phosphorylated by the enzyme; the fourth is dephosphorylated and is therefore affected by the kinase indirectly. The 80-kD protein is the kinase enzyme itself which is autophosphorylated in vitro and in the cytoskeleton. The 20-kD protein is myosin light chain. The 33- and 18-kD proteins are unidentified. The same substrates were phosphorylated when Y-1 cells were permeabilized with digitonin and incubated with [gamma-32P]ATP and phorbol 12-myristate-13-acetate. Partly purified protein kinase C changes the extent of phosphorylation of the same substrates when added to cytoskeletons previously extracted to remove endogenous protein kinase C. Addition of Ca2+, phosphatidylserine, and phorbol-12-myristate-13-acetate to cytoskeletons, and addition of these three agents plus protein kinase C to extracted cytoskeletons, causes these structures to undergo a rapid and extensive rounding. A similar change is induced in intact cells by addition of phorbol ester. It is concluded that protein kinase C is capable of changing the shape of adrenal cells by an action that involves autophosphorylation and phosphorylation of myosin light chain. This response may in turn be related to the steroidogenic responses to ACTH and cyclic AMP. PMID- 2918024 TI - Distribution of fast myosin heavy chain isoforms in thick filaments of developing chicken pectoral muscle. AB - Colloidal gold-conjugated monoclonal antibodies were prepared to stage-specific fast myosin heavy chain (MHC) isoforms of developing chicken pectoralis major (PM). Native thick filaments from different stages of development were reacted with these antibodies and examined in the electron microscope to determine their myosin isoform composition. Filaments prepared from 12-d embryo, 10-d chick, and 1-yr chicken muscle specifically reacted with the embryonic (EB165), neonatal (2E9), and adult (AB8) antimyosin gold-conjugated monoclonal antibodies, respectively. The myosin isoform composition was more complex in thick filaments from stages of pectoral muscle where more than one isoform was simultaneously expressed. In 19-d embryo muscle where both embryonic and neonatal isoforms were present, three classes of filaments were found. One class of filaments reacted only with the embryonic antibody, a second class reacted only with the neonatal specific antibody, and a third class of filaments were decorated by both antibodies. Similar results were obtained with filaments prepared from 44-d chicken PM where the neonatal and adult fast MHCs were expressed. These observations demonstrate that two myosin isoforms can exist in an individual thick filament in vivo. Immunoelectron microscopy was also used to determine the specific distribution of different fast MHC isoforms within individual filaments from different stages of development. The anti-embryonic and anti-adult antibodies uniformly decorated both homogeneous and heterogeneous thick filaments. The neonatal specific antibody uniformly decorated homogeneous filaments; however, it preferentially decorated the center of heterogeneous filaments. These observations suggest that neonatal MHC may play a specific role in fibrillogenesis. PMID- 2918026 TI - Cerebellar granule cells contain a membrane mitogen for cultured Schwann cells. AB - Proliferation of Schwann cells is one of the first events that occurs after contact with a growing axon. To further define the distribution and properties of this axonal mitogen, we have (a) cocultured cerebellar granule cells, which lack glial ensheathment in vivo with Schwann cells; and (b) exposed Schwann cell cultures to isolated granule cell membranes. Schwann cells cocultured with granule cells had a 30-fold increase in the labeling index over Schwann cells cultured alone, suggesting that the mitogen is located on the granule cell surface. Inhibition of granule cell proteoglycan synthesis caused a decrease in the granule cells' ability to stimulate Schwann cell proliferation. Membranes isolated from cerebellar granule cells when added to Schwann cell cultures caused a 45-fold stimulation in [3H]thymidine incorporation. The granule cell mitogenic signal was heat and trypsin sensitive and did not require lysosomal processing by Schwann cells to elicit its proliferative effect. The ability of granule cells and their isolated membranes to stimulate Schwann cell proliferation suggests that the mitogenic signal for Schwann cells is a ubiquitous factor present on all axons regardless of their ultimate state of glial ensheathment. PMID- 2918028 TI - Degradation rate of acetylcholine receptors inserted into denervated vertebrate neuromuscular junctions. AB - Many studies exist on the effect of denervation on the degradation of acetylcholine receptors (AChRs) at the vertebrate neuromuscular junction (nmj). These studies have described the behavior of either the total population of junctional receptors at different times after denervation, or of the receptors present at the time of denervation (referred to as original receptors). No experimental studies yet exist on the degradation rate of the receptors newly inserted into denervated junctions. In the previous studies, the original receptors of mouse sternomastoid muscles were found to retain the slow degradation (t 1/2) of approximately 8-10 d of innervated junctional receptors for up to 10 d after denervation before accelerating to a t 1/2 of approximately 3 d. The total junctional receptors, on the other hand, showed a progressive increase in degradation rate from a t 1/2 of 8-10 d to a t 1/2 of 1 d. To reconcile these earlier observations, the present study examines the degradation of new receptors inserted into the nmj after denervation. To avoid possible contamination of the data with postdenervation extrajunctional receptors, we used transmission electron microscope autoradiography to study only receptors located at the postjunctional fold of the nmj. We established that the new receptors inserted into denervated junctions have a t 1/2 of approximately 1 d, considerably faster than that of the original receptors and equivalent to that of postdenervation extrajunctional receptors. Both original and new receptors are interspersed at the top of the junctional folds. Thus, until all the original receptors are degraded, the postjunctional membrane contains two populations of AChRs that maintain a total steady-state site density but degrade at different rates. The progressive increase in turnover rate of total AChRs therefore reflects the combined rates of the original and new receptors, as earlier postulated by Levitt and Salpeter (1981). PMID- 2918027 TI - Posttranslational membrane attachment and dynamic fatty acylation of a neuronal growth cone protein, GAP-43. AB - Growth cones, the motile apparatus at the ends of elongating axons, are sites of extensive and dynamic membrane-cytoskeletal interaction and insertion of new membrane into the growing axon. One of the most abundant proteins in growth cone membranes is a protein designated GAP-43, whose synthesis increases dramatically in most neurons during periods of axon development or regeneration. We have begun to explore the role of GAP-43 in growth cone membrane functions by asking how the protein interacts with those membranes. Membrane-washing experiments indicate that mature GAP-43 is tightly bound to growth cone membranes, and partitioning of Triton X-114-solubilized GAP-43 between detergent-enriched and detergent-depleted phases indicates considerable hydrophobicity. The hydrophobic behavior of the protein is modulated by divalent cations, particularly zinc and calcium. In vivo labeling of GAP-43 in neonatal rat brain with [35S]methionine shows that GAP-43 is initially synthesized as a soluble protein that becomes attached to membranes posttranslationally. In tissue culture, both rat cerebral cortex cells and neuron like PC12 cells actively incorporate [3H]palmitic acid into GAP-43. Isolated growth cones detached from their cell bodies also incorporate labeled fatty acid into GAP-43, suggesting active turnover of the fatty acid moieties on the mature protein. Hydrolysis of ester-like bonds with neutral hydroxylamine removes the bound fatty acid and exposes new thiol groups on GAP-43, suggesting that fatty acid is attached to the protein's only two cysteine residues, located in a short hydrophobic domain at the amino terminus. Modulation of the protein's hydrophobic behavior by divalent cations suggests that other domains, containing large numbers of negatively charged residues, might also contribute to GAP-43-membrane interactions. Our observations suggest a dynamic and reversible interaction of GAP-43 with growth cone membranes. PMID- 2918029 TI - Complete thrombospondin mRNA sequence includes potential regulatory sites in the 3' untranslated region. AB - The nucleotide sequence of human thrombospondin (TS) mRNA has been determined from human fibroblast and endothelial cDNAs. The sequence of 5802 bp begins 110 bp upstream from the initiator codon and includes the entire 3' untranslated region (UTR) of the mRNA. The coding region (3510 bp) specifies a protein of 1170 amino acids with all of the known features of the TS subunit (Frazier, W. A. 1987. J. Cell Biol. 105:625-632). The long 3' UTR of 2166 nucleotides is extremely A/T-rich, particularly in the latter half. It contains 37 TATT or ATTT(A) sequences that have been suggested as mediators of the stability of mRNAs for cytokines, lymphokines, and oncogenes (Shaw, G., and R. Kamen. 1986. Cell. 46:659-667). Another unusual feature of the 3' UTR of TS mRNA is a stretch of 42 nucleotides of which 40 are thymidines (uridine in the mRNA) including an uninterrupted sequence of 26 thymidines. This region is flanked by two sets of direct repeats suggesting that it may be an insertion element of retrotranscriptional origin. Comparison of the 3' untranslated region of TS mRNA with the GenBank data base indicates the greatest degree of similarity with an alpha-interferon gene which contains a number of the TATT/ATTT consensus sites. The degree of similarity between the TS and interferon sequences is the same in regions of the interferon gene corresponding to its coding and noncoding regions suggesting that most of the TS 3' UTR may be derived from an interferon gene or pseudogene. The features of the TS mRNA 3' UTR provide a potential explanation for the rapid regulation of TS message observed in cultured cells in response to PDGF and suggest that TS is a member of a group of proteins which are intimately involved in the control of cell growth and differentiation. PMID- 2918030 TI - Selective release from cultured mammalian cells of heat-shock (stress) proteins that resemble glia-axon transfer proteins. AB - Cultured rat embryo cells were stimulated to rapidly release a small group of proteins that included several heat-shock proteins (hsp110, hsp71, hscp73) and nonmuscle actin. The extracellular proteins were analyzed by two-dimensional polyacrylamide gel electrophoresis. Heat-shocked cells released the same set of proteins as control cells with the addition of the stress-inducible hsp110 and hsp71. Release of these proteins was not blocked by either monensin or colchicine, inhibitors of the common secretory pathway. A small amount of the glucose-regulated protein grp78 was externalized by this pathway. The extracellular accumulation of these proteins was inhibited after they were synthesized in the presence of the lysine analogue aminoethyl cysteine. It is likely that the analogue-substituted proteins were misfolded and could not be released from cells, supporting our conclusion that a selective release mechanism is involved. Remarkably, actin and the squid heat-shock proteins homologous to rat hsp71 and hsp110 are also among a select group of proteins transferred from glial cells to the squid giant axon, where they have been implicated in neuronal stress responses (Tytell et al.: Brain Res., 363:161-164, 1986). Based in part on the similarities between these two sets of proteins, we hypothesized that these proteins were released from labile cortical regions of animal cells in response to perturbations of homeostasis in cells as evolutionarily distinct as cultured rat embryo cells and squid glial cells. PMID- 2918031 TI - Kinetic characteristics and regulation of hexose transport in a galactokinase negative Chinese hamster fibroblast cell line: a good model for studies on sugar transport in cultured mammalian cells. AB - We report the kinetic characteristics for D-galactose, 2-deoxy-D-glucose and 3-O methyl-D-glucose transport in a galactokinase null-allele mutant of a Chinese hamster V79 cell line. GalKl cells exhibited a Km and Vmax for D-galactose, 2 deoxy-D-glucose, and 3-O-methyl-D-glucose transport of 8.6 +/- 2.6 mM and 26.1 +/ 7.2 nmol/mg p/min, 4.1 +/- 1.2 mM and 40.3 +/- 9.5 nmol/mg p/min, and 7.01 +/- .85 mM and 11.6 +/- 4.8 nmol/mg p/30 s, respectively. Nonsaturable hexose uptake was determined using cytochalasin B inhibition of galactose uptake (89.6 +/- 3.7% of galactose uptake was cytochalasin B inhibitable) and L-glucose uptake (7.5% of the galactose uptake). D-Galactose was not metabolized and effluxed rapidly from preloaded cells. The Kls for the inhibition of D-galactose transport were 4.5 +/- 2.5 mM for D-glucose, 7.0 +/- 2.0 mM for 2-deoxy-D-glucose, 6 mM for 2-deoxy-D galactose and 6.0 +/- 0.6 mM for 3-O-methyl-D-glucose. This indicates the operation of a single common carrier. The hexose transport rate decreased 50-60% after 24 h serum deprivation. Addition of insulin was shown to increase hexose transport (more than twofold) in serum-deprived cells. Hexose transport rates increased substantially in glucose-deprived, D-fructose- or D-galactose-fed cells as compared to glucose-fed cells. Since GalKl does not metabolize galactose, the hexose transport increases induced by feeding cells galactose suggest that carrier interaction with ligand is not a significant factor in transport regulation in GalKl. The kinetic and regulatory characteristics of D-galactose transport in the GalKl cell line indicate that this system is a good model to study sugar transport from a mechanistic and regulatory point of view. PMID- 2918032 TI - Regulation of skeletal muscle satellite cell proliferation and differentiation by transforming growth factor-beta, insulin-like growth factor I, and fibroblast growth factor. AB - Skeletal muscle satellite cells were cultured from mature rats and were treated in vitro with various combinations of transforming growth factor (TGF)-beta, fibroblast growth factor (FGF), and insulin-like growth factor I (IGF-I). In serum-free defined medium the following observations were made: TGF-beta depressed proliferation and inhibited differentiation; FGF stimulated proliferation and depressed differentiation; IGF-I stimulated proliferation to a small degree but demonstrated a more pronounced stimulation of differentiation. In evaluating combinations of these three factors, the differentiation inhibiting effect of TGF-beta could not be counteracted by any combination of IGF-I or FGF. The proliferation-depressing activity of TGF-beta, however, could not inhibit the mitogenic activity of FGF. Maximum stimulation of proliferation was observed in the presence of both FGF and IGF-I. The highest percentage fusion was also observed under these conditions, but differentiation with minimal proliferation resulted from treatment with IGF-I, alone. By altering the concentrations of TGF beta, FGF, and IGF-I, satellite cells can be induced to proliferate, differentiate, or to remain quiescent. PMID- 2918033 TI - Evidence for a major route for zinc uptake in human red blood cells: [Zn(HCO3)2Cl]- influx through the [Cl-/HCO3-] anion exchanger. AB - The initial rate of Zn2+ uptake in human red cells was measured by atomic absorption. A very important fraction of Zn2+ uptake was inhibited by DIDS with IC50 = 0.3 microM (and by furosemide and bumetanide with IC50 of 200 and 500 microM, respectively). DIDS-sensitive Zn2+ uptake exhibited the following properties: 1) It required the simultaneous presence of both external HCO3- and Cl-. 2) In Cl- containing media, it was strongly stimulated by external HCO3- following a sigmoidal (S-shaped) and saturable function, which was fitted by a Hanes equation, with n = 2 and an apparent dissociation constant (for external HCO3-) of 5.3 +/- 0.9 mM (mean +/- SD of four experiments). The maximal rate of Zn2+ uptake at saturating HCO3- concentrations was 50.7 +/- 4.8 mmol (liter cells x h)-1. 3) In HCO3- containing media, it was strongly stimulated by external Cl- following a Michaelis-like equation with an apparent dissociation constant (for external Cl-) of 88 +/- 11 mM (mean +/- SD of three experiments). 4) Bicarbonate stimulated Zn2+ uptake was inhibited by physiological concentrations of phosphate (sulfate was a much less potent inhibitor than phosphate). A kinetic analysis of the data strongly suggested that zinc was transported by the anion carrier in the form of the monovalent anion complex: [Zn(HCO3)2Cl]-. PMID- 2918034 TI - Stimulation of cartilage-matrix proteoglycan synthesis by morphologically transformed chondrocytes grown in the presence of fibroblast growth factor and transforming growth factor-beta. AB - The effects of transforming growth factor-beta (TGF-beta) on the synthesis of cartilage-matrix proteoglycan by cultured rabbit chondrocytes were examined. Rabbit chondrocytes were seeded at low density and exposed to a 1:1 mixture of Dulbecco's modified Eagle's medium and Ham's F-12 medium supplemented with 0.5% fetal bovine serum, 1% bovine serum albumin, 50 micrograms/ml ascorbic acid, and 2 x 10(-7) M hydrocortisone (Medium A). Various combinations of TGF-beta, insulin like growth factor-I (IGF-I), and fibroblast growth factor (FGF) were also added to Medium A, and the chondrocytes were grown to confluency. Chondrocytes grown with TGF-beta or FGF alone became flat or fibroblastic, those grown with FGF and TGF-beta became very elongated and formed distinct foci, and those grown with FGF and IGF-I showed the spherical configuration characteristic of overtly differentiated chondrocytes. Nevertheless, the incorporation of 3H with glucosamine into the large, chondroitin sulfate proteoglycan synthesized by cultures with FGF and TGF-beta was similar to that in cells grown with FGF and IGF-I and five times that in cells cultured with FGF alone. The increases in incorporation of 3H reflected real increases in proteoglycan synthesis, because chemical analyses showed an increase in the accumulation of macromolecules containing uronic acid in cultures with FGF and TGF-beta or with FGF and IGF-I. However, FGF in combination with either TGF-beta or IGF-I had little effect on the incorporation of 3H into small proteoglycans or hyaluronic acid. These results indicate that chondrocytes morphologically transformed with TGF-beta and FGF fully express the differentiated proteoglycan phenotype rather than the transformed glycosaminoglycan phenotype. PMID- 2918035 TI - Regulation of hexose transport in rat myoblasts during growth and differentiation. AB - We report here the effects of growth conditions and myogenic differentiation on rat myoblast hexose transport activities. We have previously shown that in undifferentiated myoblasts the preferred substrates for the high (HAHT)- and low (LAHT)-affinity hexose transport systems are 2-deoxyglucose (2-DG) and 3-O-methyl D-glucose (3-OMG), respectively. The present study shows that at cell density higher than 4.4 x 10(4) cells/cm2, the activities of both transport processes decrease with increasing cell densities of the undifferentiated myoblasts. Since the transport affinities are not altered, the observed decrease is compatible with the notion that the number of functional hexose transporters may be decreased in the plasma membrane. Myogenic differentiation is found to alter the 2-DG, but not the 3-OMG, transport affinity. The Km values of 2-DG uptake are elevated upon the onset of fusion and are directly proportional to the extent of fusion. This relationship between myogenesis and hexose transport is further explored by using cultures impaired in myogenesis. Treatment of cells with 5 bromo-2'-deoxyuridine abolishes not only myogenesis but also the myogenesis induced change in 2-DG transport affinity. Similarly, alteration in 2-DG transport affinity cannot be observed in a myogenesis-defective mutant, D1. However, under myogenesis-permissive condition, the myogenesis of this mutant is also accompanied by changes in its 2-DG transport affinity. The myotube 2-DG transport system also differs from its myoblast counterpart in its response to sulfhydryl reagents and in its turnover rate. It may be surmised from the above observations that myogenesis results in the alteration of the turnover rate or in the modification of the 2-DG transport system. Although glucose starvation has no effect on myogenesis, it is found to alter the substrate specificity and transport capacity of HAHT. In conclusion, the present study shows that hexose transport in rat myoblasts is very sensitive to the growth conditions and the stages of differentiation of the cultures. This may explain why different hexose transport properties have been observed with myoblasts grown under different conditions. PMID- 2918036 TI - Effect of retinoic acid on the phosphorylation of endogenous proteins in HL-60 cells. AB - HL-60 cells were incubated with [32P]-Pi in order to label endogenous phosphoproteins in situ. These were then resolved via two-dimensional electrophoresis and autoradiograms were made from the gels. A comparison of autoradiograms made from retinoic-acid-differentiated cells with those made from control cells revealed a small number of phosphoproteins whose labeling was enhanced in differentiated cells. Incubating HL-60 cells with [35S]-methionine revealed that RA induced the synthesis of one of these proteins, (53 kDa, pl 4.8) although not to a degree sufficient to account for the increased phosphate labeling observed in differentiated cells. Difluoromethylornithine (DFMO), which arrests HL-60 cell proliferation without inducing differentiation, had no effect on endogenous protein phosphorylation. Treatment of DFMO-arrested cells with retinoic acid, however, increased the phosphorylation of the proteins and resulted in differentiation of the cells. Densitometric analysis of autoradiograms made from two-dimensional gels revealed that the phosphorylation of the 53-kDa, pl 4.8 protein was significantly elevated in cells exposed to RA for as little as 12 hours, i.e., before the cells were committed to differentiate and before a significant increase in the number of phenotypically mature cells was observed. It therefore appears that this protein may be an intermediate in the retinoic-acid-induced differentiation process. PMID- 2918037 TI - Analysis of the multiple 5' and 3' termini of poly(A)+ and poly(A)-deficient thymidylate synthase mRNA in growth-stimulated mouse fibroblasts. AB - Thymidylate synthase (TS) mRNA content increases about 20-fold when growth stimulated mouse cells progress from the G0/G1 phase into the S phase of the cell cycle. Previous studies, using a cell line in which the TS gene is amplified (LU3 7), indicated that transcriptional initiation as well as polyadenylation of the mRNA occur at several locations in unsynchronized cells. In the present study, we have used S1 nuclease protection assays to analyze the possible significance of the multiple transcriptional initiation and polyadenylation sites. We found that the same pattern of 5' and 3' termini were detected with RNA isolated from the overproducing cells as with RNA isolated from the parental mouse 3T6 cell line, demonstrating that the heterogeneous termini are not a consequence of gene amplification. There was no change in the pattern of 5' or 3' termini with either cell line during the progression from G1 phase through S phase in serum stimulated cells. Therefore, the increase in TS mRNA content is not the result of differential utilization of the various transcriptional initiation or polyadenylation sites. Analyses of poly(A)- deficient cytoplasmic TS RNA showed that the 5' termini were the same as those found in poly(A) + mRNA. However, the 3' termini were extremely heterogeneous in length. Although some of the poly(A)- deficient RNA extended beyond the normal site of polyadenylation, most of it was shorter than full-length TS mRNA. PMID- 2918038 TI - Differences of Ca2+ regulation in skin fibroblasts from blacks and whites. AB - Black people have a higher propensity than caucasians toward essential hypertension. To explore the possibility that this racial difference relates to cellular Ca2+ metabolism, we measured 45Ca2+ washout and uptake and cytosolic free concentration of Ca2+ [Ca2+]i in serially passed skin fibroblasts from normotensive black and white males. Depending on the experimental conditions, 45Ca2+ washout in these cells was described by either two or three exponential functions, whereas 45Ca2+ uptake was described only by a two-exponent function. There were no racial differences in 45Ca2+ uptake and washout of unstimulated fibroblasts. However, stimulation by human serum resulted in an increase in the 45Ca2+ washout that was higher in fibroblasts from blacks than from whites. The racial differences were expressed primarily by higher values of the apparent washout rate constant (k1) of 45Ca2+ from the largest and most rapidly exchangeable cellular pool. The effect of human serum was not related to its origin (blacks vs. whites). In 2 mM Ca2+ medium and 10% serum from blacks, the respective k1 (mean +/- SEM; x 10(-2)/min) values for fibroblasts from blacks and whites were 89.68 +/- 5.23 and 73.29 +/- 4.0; in the presence of 10% serum from whites, the k1 values for cells from blacks and whites were 84.14 +/- 2.80 and 76.36 +/- 3.23 (overall significance of P less than .01). In Ca2+-deficient medium in the presence of 10% human serum, the k1 for fibroblasts from blacks and whites were 115.57 +/- 3.76 and 102.15 +/- 3.30 (P less than .05). Serum substantially increased the 45Ca2+ uptake in fibroblasts from both blacks and whites; however, racial differences were not observed. Basal levels of [Ca2+]i were not different in fibroblasts of blacks vs. whites (46.8 +/- 6.8 and 43.2 +/- 7.1 nM for blacks and whites, respectively). However, the peak response of Cai2+ transients for cell stimulated by 5% human serum was significantly higher in blacks than whites (blacks = 963 +/- 213, whites = 481 +/- 162 nM; P = .0286). We conclude that Ca2+ regulation is different in serum-stimulated fibroblasts from blacks and whites and that, at least in part, this difference may relate to a greater agonist-induced mobilization of Ca2+ in fibroblasts from blacks. PMID- 2918039 TI - Ionic dependence of the extracellular ATP-induced permeabilization of transformed mouse fibroblasts: role of plasma membrane activities that regulate cell volume. AB - Extracellular ATP rendered the plasma membrane of transformed mouse fibroblasts permeable to normally impermeant molecules. This permeability change was prevented by increasing the ionic strength of the isotonic medium with NaCl. Conversely, the cells exhibited increased sensitivity to ATP when the NaCl concentration was decreased below isotonicity, when the KCl concentration was increased above 5 mM while maintaining isotonicity, and when the pH of the medium was raised above 7.0. These conditions as well as the addition of ATP itself caused cell swelling. However, the effect of ATP was independent of cell volume and dependent upon the ionic strength and not the osmolarity of the medium since 1) addition of sucrose to isotonic medium did not prevent permeabilization although media made hypertonic with either sucrose or NaCl caused a decrease in cell volume; and 2) addition of sucrose or NaCl to hypotonic media caused a decrease in cell volume, but only NaCl addition decreased the response to ATP. Conditions that have been shown to inhibit plasma membrane proteins that play a reciprocal role in cell volume regulation had reciprocal effects on the permeabilization process, even though the effect of ATP was independent of cell volume. For example, inhibition of the Na+,K+-ATPase by ouabain increased sensitivity of cells to ATP while conditions which inhibit Na+,K+,Cl- cotransporter activity, such as treatment of the cells with the diuretics furosemide or bumetanide or replacement of sodium chloride in the medium with sodium nitrate or thiocyanate, inhibited permeabilization. The furosemide concentration that inhibited permeabilization was greater than the concentration that inhibited Na+,K+,Cl- -cotransporter-mediated 86Rb+ (K+) uptake, suggesting that the effect of furosemide on the permeabilization process may not be specific for the Na+,K+,Cl- -cotransporter. PMID- 2918040 TI - Regrowth kinetics of cells from different regions of multicellular spheroids of four cell lines. AB - A basic understanding of the recruitment of quiescent tumor cells into the cell cycle would be an important contribution to tumor biology and therapy. As a first step in pursuing this goal, we have investigated the regrowth kinetics of cells from different regions in multicellular spheroids of rodent and human origin. Cells were isolated from four different depths within the spheroids using a selective dissociation technique. The outer cells were proliferating and resumed growth after replating with a 0-8-hour lag period, similar to cells from exponentially growing monolayers. With increasing depth of origin, the lag periods prior to regrowth increased to 2-3 times the monolayer doubling time; cells from plateau-phase monolayers showed a lag period of 1-1.5 times the doubling period. After resuming growth, all cells of a given cell line grew with the same doubling time and achieved the same confluency level. The inner spheroid cells and cells from plateau-phase monolayers had reduced clonogenic efficiencies. The inner cells were initially 1.5-3 times smaller than the outer cells, but began to increase in volume within 4 hours of replating. The fractions of S-phase cells were greatly decreased with increasing depth of origin in the spheroids; there were long delays prior to S-phase recovery after plating, to a maximum of 1-1.5 times the normal doubling time. These results suggest that those quiescent cells from spheroids and monolayers which are able to reenter the cell cycle are predominantly in the G1-phase. However, quiescent cells from the innermost spheroid region require approximately twice as long to enter normal cell cycle traverse as cells from plateau-phase monolayers. The selective dissociation method can isolate very pure populations of proliferating and quiescent cells in a rapid and nonperturbing manner; this system will be valuable in further characterizing quiescent cells from spheroids. PMID- 2918041 TI - Identification of a 15,000-molecular-weight form of immunoreactive transforming growth factor alpha in extracts of porcine pituitary. AB - Two different mitogenic activities were identified from extracts of porcine pituitary by using COMMA-D mouse mammary epithelial cells in a serum-free 3H thymidine incorporation assay. Porcine pituitaries were extracted in phosphate buffered saline (pH 7.4) and 25-80% (NH4)2SO4 pellets were dialyzed and chromatographed by using DEAE-Sepharose chromatography (pH 8.0), resulting in two peaks (I and II) of mitogenic activity. Peak I represented a recovery of 73% of the units of mitogenic activity present in crude extract of pituitary while only 1.25% of the activity was recovered in peak II. Peak I was further purified by using CM-Sephadex and heparin-Sepharose chromatographies and yielded a mitogen that was able to elicit one-half-maximal stimulation of 3H-thymidine incorporation by COMMA-D cells at 48 pg/ml. As expected with pituitary as the tissue source, peak I was confirmed to be basic fibroblast growth factor (bFGF) by using specific antibodies in enzyme-linked immunosorbent assay and Western immunoblotting procedures. Peak II was further purified by using chromatofocusing (pH 7.3-5.0), reverse-phase, and cation-exchange HPLCs. The mitogenic activity eluted at pH 6.3 from chromatofocusing, migrated as a 13-kDa molecule on gel filtration HPLC, and did not bind to heparin-Sepharose under conditions which bound fibroblast growth factors. The material purified from peak II and rat synthetic transforming growth factor alpha (TGF alpha) competed in a parallel fashion with 125I-epidermal growth factor for receptor binding with A431 human epidermal carcinoma cells. In addition, the mitogen purified from peak II showed a single immunoreactive band migrating at 15 kDa when specific antiserum against TGF alpha was used in a Western immunoblotting procedure. The data suggest that in addition to the well-documented presence of bFGF, normal adult porcine pituitaries contain a 15-kDa form of immunoreactive TGF alpha that binds to EGF receptors and is mitogenic for mammary epithelial cells. PMID- 2918042 TI - Characterization of polyclonal antibodies that distinguish acidic and basic fibroblast growth factors by using western immunoblotting and enzyme-linked immunosorbent assays. AB - Rabbit polyclonal antibodies were raised against ovalbumin conjugates of purified bovine brain acidic fibroblast growth factor (aFGF) and a synthetic peptide containing the N alpha-terminal 1-24 amino acid sequence of bovine basic fibroblast growth factor (bFGF). These antibodies were used to specifically detect 1-ng quantities of aFGF and bFGF by using enzyme-linked immunosorbent assay (ELISA) and Western immunoblot procedures. Antibodies raised against aFGF recognized bovine brain aFGF and bovine recombinant aFGF but very poorly recognized recombinant bFGF or purified porcine or bovine pituitary bFGF with ELISA and Western immunoblot procedures. Antibodies raised against bFGF (1-24) recognized purified bovine, porcine, and recombinant human bFGF but only very poorly recognized aFGF with ELISA and Western immunoblot procedures. In vitro addition of anti-bFGF antibodies was able to partially neutralize bFGF-stimulated 3H-thymidine incorporation by COMMA-D mouse mammary epithelial cells while having no effect on aFGF or epidermal growth factor (EGF) stimulation. In vitro addition of anti-aFGF antibodies had no effect on bFGF- or EGF-stimulated 3H-thymidine incorporation, but surprisingly, had a potentiating effect on aFGF stimulation. Antibodies against aFGF immobilized on protein A-Sepharose were able to specifically and completely remove mitogenic activity from solutions containing aFGF but had no effect on removal of mitogenic activity from control solutions containing bFGF or EGF. Similarly, immobilized anti-bFGF antibodies completely removed mitogenic activity from solutions of bFGF, but not aFGF or EGF controls. These antibodies have been useful for the identification and characterization of growth factors from tissue and recombinant sources. PMID- 2918043 TI - A mammary-derived growth inhibitor (MDGI) related 70 kDa antigen identified in nuclei of mammary epithelial cells. AB - The aim of the present study was to investigate the expression of the mammary derived growth inhibitor (MDGI) and the subcellular localization of MDGI-related antigens in bovine mammary glands. Cell-free translation of poly(A+) = RNA, immunoprecipitation with rabbit anti-MDGI-antibodies, and estimation of the relative contents of MDGI by a radioimmunoassay in mammary tissue of different functional states revealed that the 13 kDa MDGI was dramatically increased in terminally differentiated mammary tissue compared with the proliferating tissue from pregnant animals. To address the question of tissue localization, polyclonal anti-MDGI antibodies and antibodies directed against a synthetic peptide corresponding to residues 69 to 78 of MDGI were used. Western blotting of tissue fractions revealed the cytosolic and microsomal localization of MDGI. Additionally, both types of antibodies detected a 70-kDa antigen in the nuclear fraction of differentiated mammary glands. Salt extraction and DNase I digestion of isolated nuclei, as well as chromatin purification, indicated an association of the 70-kDa antigen with the chromatin. By means of the immunogold technique, MDGI-related antigens were localized within euchromatic nuclear regions of epithelial cells in the intact differentiated mammary gland. The immunostaining was markedly diminished in the proliferating tissue. This finding raises the possibility that MDGI and the 70-kDa antigen influence cell proliferation by acting on gene expression within the nuclei of mammary glands. PMID- 2918045 TI - Metabolism of small RNAs in cultured human cells. AB - There are gaps in what is known about the metabolism of some mammalian small RNA species. Our present observations can be summarized as follows. The level of radiolabeled mature U1 RNA doubled between 2 and 24 hr of label chase, while that of all other small RNA species tested did not change. These results are compatible with the possibility that the nucleotide precursor pool for U1 RNA transcription may be partly segregated, or that there may be a second pathway of U1 RNA formation. Precursors of nucleolar U3 RNA were detected whose electrophoretic mobilities are equivalent to those of transcripts approximately 14 and approximately 8 nucleotides longer than the mature species, and which are apparently cytoplasmic. The ladder of U2 RNA precursors showed a gap, suggesting that some of the cleavages during U2 RNA processing are endonucleolytic. We detected an apparent U5 RNA precursor whose electrophoretic mobility is equivalent to that of a species approximately 1 nucleotide longer than mature U5 RNA. There was a predominant band in the middle of the ladder of U4 RNA precursors (apparently approximately 3 nucleotides longer than mature U4 RNA) which suggests that U4 RNA maturation may pause briefly at that intermediate. There are apparently two additional species of mature hY3 RNA, which are less abundant and are about 1 and 2 bases longer than the major hY3 RNA species. An apparent hY3 RNA precursor was detected, which may be approximately 2-3 nucleotides longer than the main mature hY3 RNA species. PMID- 2918044 TI - Heparin interactions with cultured human vascular endothelial and smooth muscle cells: incidence on vascular smooth muscle cell proliferation. AB - The binding, internalization, and metabolism of [3H]-heparin by human umbilical vein endothelial cells (HUVEC) and human umbilical arterial smooth muscle cells (HUASMC) have been characterized using size-exclusion HPLC. Incubation of HUVEC with [3H]-heparin demonstrated selective binding of high-molecular-weight (MW) components (MW = 21 kd), which was followed by rapid, temperature-dependent internalization. Over the next 3 hours, this internalized [3H]-heparin was degraded to low-MW fragments (MW = 0.9 kd). Primary cultures of HUASMC selectively bound extremely high-MW components (MW = 40 kd) and also smaller components whose MW (0.9 kd) corresponded to that of the heparin metabolite(s) formed by HUVEC. Subcultured HUASMC bound only the 40-kd components. Internalization of heparin by smooth muscle cells (SMC) was significantly slower than that determined for HUVEC, and even after 4 hours there was no evidence of the heparin being metabolized. However, when incubating primary rabbit aortic SMC with purified low-MW heparin fragment(s) produced in culture by HUVEC, a significantly lower proliferative response of these cells (IC50 = 18.4 micrograms/ml) was obtained. Virtually no effect was observed with subcultured SMC in the range of the tested concentrations (0-20 micrograms/ml). These fragments were 10- to 15-fold more effective in inhibiting primary SMC growth than was standard heparin. Furthermore, heparin fractions in the same range of molecular weights, purified either after nitrous acid or heparinase depolymerization of standard heparin, showed no activity on primary SMC growth, thus indicating a high degree of selectivity of the heparin metabolite(s) produced by HUVEC in culture. PMID- 2918046 TI - Distribution of RU 486 and its demethylated metabolites in humans. AB - The concentrations of RU 486 and its demethylated metabolites were determined by RIA in samples of myometrium, abdominal adipose tissue, and serum, which were collected at hysterectomies performed 12-15 h after oral administration of 200 mg RU 486. The RU 486 concentrations in myometrium were similar in the five women studied, with a mean of 148 +/- 58 (+/- SD) ng/g (344 +/- 135 pmol/g). The adipose tissue RU 486 levels varied more, the mean concentration being 447 +/- 191 ng/g (1041 +/- 445 pmol/g). The serum RU 486 concentrations ranged from 175 899 ng/ml [mean, 396 +/- 259 ng/mL (922 +/- 603 nmol/L)]. In these women the nonprotein-bound fraction of [6,7-3H]RU 486 varied from 1.4-3.1% (mean, 2.3%). The approximate concentrations of the combined mono- and didemethylated metabolites of RU 486 were 1.4, 3.1, and 5.2 times higher in adipose tissue, myometrial tissue, and serum, respectively, than those of the parent RU 486. In vitro, rapid and nonsaturable accumulation of [6,7-3H]RU 486 from phosphate buffer into adipose tissue was inhibited by the addition of alpha 1-acid glycoprotein, the specific serum transport protein for RU 486, to the buffer medium. Accumulation of [6,7-3H]RU 486 in myometrial specimens was poor. The enterohepatic cycling of RU 486 was assessed in four normal subjects by repetitive intake of charcoal subsequent to ingestion of 200 mg RU 486. Compared to other normal subjects, the serum levels and areas under the concentration curves were lower and t1/2 values shorter in the group given charcoal, suggesting that in vivo RU 486 may be partly pooled in the enterohepatic cycle. Our studies suggest that despite the low volume of distribution and the effective serum binding of RU 486, the myometrial and adipose tissue concentrations of RU 486 and its metabolites were similar (approximately 10(-9)-10(-10) mol/g) after oral intake of RU 486. PMID- 2918047 TI - Immunoreactive beta-casomorphin-8 in cerebrospinal fluid from pregnant and lactating women: correlation with plasma levels. AB - We measured plasma and cerebrospinal fluid (CSF) beta-casomorphin-8, a product of beta-casein hydrolysis which has opioid activity, by RIA in women during late pregnancy and lactation and in nonpregnant nonpuerperal women. Before RIA, the samples were acidified and extracted by reverse phase silica gel chromatography, which removed most of the beta-casein. Lactating women had a significantly higher mean plasma beta-casomorphin-8 concentration (2.66 nmol/L; n = 8) than women in late pregnancy (0.82 nmol/L; n = 8) and nonpregnant women (0.32 nmol/L; n = 5). The CSF beta-casomorphin-8 concentration also was significantly higher in lactating women (mean, 0.35 nmol/L; n = 8) than during late pregnancy (0.22 nmol/L; n = 8) or in nonpregnant women (0.15 nmol/L; n = 5). A positive correlation was found between plasma and CSF beta-casomorphin-8 levels in the entire study group. The milk beta-casomorphin-8 concentration, measured in five puerperal women, averaged 19.8 nmol/L. Thus, there is a decreasing concentration gradient between milk and plasma and between plasma and CSF. Chromatographic analysis revealed mol wt heterogeneity of the RIA-active material. In CSF at least three different components were detected, two of mol wt around 900-2,000 and one of approximately 12,000. One of the low mol wt components coeluted in several chromatographic systems with synthetic beta-casomorphin-8 (mol wt, 900). Such a component was not found in milk or plasma, in which the major activity was due to larger sized peptides. The major peaks in milk were around 1,500-2,000 and 12,000 mol wt, corresponding to the larger peaks in CSF. The results suggest that fragments of the milk protein beta-casein may cross the breast parenchyma-blood barrier into plasma and subsequently penetrate the blood-brain barrier to reach the central nervous system. Thus, mammary tissue may assume endocrine function during galactopoiesis, and beta-casein could be considered a prohormone. PMID- 2918048 TI - Pharmacokinetics and metabolism of neurotensin in man. AB - We studied the pharmacokinetics, arteriovenous extraction, and degradation sites of neurotensin (NT) in man during iv infusions of synthetic intact NT [NT-(1-13)] and the NH2-terminal metabolite NT-(1-8) during lipid ingestion and by catheterization of various vascular beds in normal subjects and patients with hepatic disease. NT-like immunoreactivities in plasma were quantitated using 2 sequence-specific RIAs and gel filtration chromatography. During iv infusion of NT-(1-13) in 6 normal subjects, the median t1/2 was 1.7 min (interquartile range, 0.7-2.8), the MCR was 36 mL/kg.min (range, 21-54), and distribution space was 78.8 mL/kg (range, 56-91). The results were similar at infusion rates of 72, 144, and 288 pmol/kg.h (n = 6). During infusion of NT-(1-8) in 7 normal subjects, the median t1/2 was 8.3 min (range, 4.7-13.8), the MCR was 11.0 mL/kg.min (range, 6.7 21.7), and the distribution space was 142.6 mL/kg (range, 45.3-281.0). Significant peripheral arteriovenous extraction of NT-(1-13) was found at infusion rates of 144 and 288 pmol/kg.h. Extraction of NH2-terminal immunoreactivity was not significant. Intact NT was identified by gel chromatography in arterial plasma after lipid ingestion and iv infusion of NT-(1 13), but postprandially in only low concentrations. In 17 patients with various nonhepatic diseases, plasma intact NT levels were not different in blood sampled from the renal vein, inferior vena cava, brachial artery, or hepatic vein. In contrast, NH2-terminal immunoreactivity was significantly higher in hepatic venous than in systemic plasma. In 6 patients with hepatic disease, systemic plasma intact NT levels were increased, but even more so in hepatic venous plasma. These results demonstrate that metabolism of intact NT is rapid, and a significant peripheral arterio-venous extraction is present. Further studies are necessary to establish if the liver is a site of degradation of intact NT in man. PMID- 2918050 TI - Serum bioactive parathyroid hormone in hemodialysis patients. AB - In 41 hemodialysis patients with bone disease (histological diagnosis with histomorphometric confirmation of PTH activity) results from a serum immunoreactive PTH (iPTH) assay correlated with results from a new serum bioactive PTH (bio-PTH) assay (r = 0.84; P less than 0.001). The serum bio-PTH values correlated well with osteoclast numbers (r = 0.70; P less than 0.001), resorption surfaces (r = 0.55; P less than 0.001), and presence of marrow fibrosis (P less than 0.02). The serum iPTH values also correlated with osteoclast numbers (r = 0.61; P less than 0.001), resorption surfaces (r = 0.47; P less than 0.003), and presence of marrow fibrosis (P less than 0.02). Serum bio PTH and iPTH values were higher in patients with severe hyperparathyroidism than in other patients. The assays were equally useful in identifying dialysis patients with severe hyperparathyroidism. Patients with osteomalacia or low turnover bone disease had low serum bio-PTH and/or iPTH values. Low bio-PTH values (less than or equal to 3.6 pmol/L) had a sensitivity and a specificity of 93% for osteomalacia or low turnover bone disease. Low bio-PTH values also were useful in identifying those patients with positive aluminum staining in bone. The serum bio-PTH assay was useful in identifying patients with osteomalacia, low turnover bone disease, or aluminum accumulation. PMID- 2918049 TI - Reversible alteration of red cell lithium-sodium countertransport in patients with thyroid disease. AB - Thyroid hormones may alter red blood cell (RBC) sodium content and transport. The functional importance of lithium-sodium (Li-Na) countertransport in regulating sodium (Na) transport in vascular smooth muscle and kidney by Na-H countertransport and the potential effect of thyroid hormone on these processes led us to study Li-Na countertransport and other sodium transporters in RBCs of patients with thyroid dysfunction. Patients with untreated hypothyroidism (10) and hyperthyroidism (10) were studied, along with normal subjects (10). The mean value for Li-Na countertransport was significantly higher in the hypothyroid group [0.46 +/- 0.08 (+/- SE) mmol/L cell.h; P less than 0.05] and lower in the hyperthyroid group (0.15 +/- 0.04 mmol/L cell.h; P less than 0.05) compared to that in the normal subjects (0.25 +/- 0.03 mmol/L cell.h). When all groups were combined, significant negative correlations were found between Li-Na countertransport and serum T4 (r = -0.48; P less than 0.01), free T4 index (r = 0.42; P less than 0.05), and serum T3 (r = -0.38; P less than 0.05). Li-Na countertransport was positively correlated with serum triglyceride (r = 0.57; P less than 0.01), but not with serum cholesterol levels (r = 0.28; P = NS). The values became normal in subsets of the hypothyroid (n = 5) and hyperthyroid groups (n = 5) during treatment. We found a bidirectional effect of thyroid status on RBC Li-Na countertransport, which was reversible when serum thyroid hormone levels became normal. Changes in Li-Na countertransport, a pathway of Na H exchange, may influence renal sodium handling and vascular tone in patients with thyroid disease and contribute to abnormalities such as hypertension that occur in patients with hypothyroidism. PMID- 2918051 TI - Chronic treatment with pirenzepine decreases growth hormone secretion in insulin dependent diabetes mellitus. AB - We and others previously reported that nocturnal GH secretion in patients with insulin-dependent diabetes mellitus is blunted by acute cholinergic muscarinic blockade with pirenzepine. In this study, we investigated whether this inhibitory effect on GH secretion persists during chronic pirenzepine administration, and if pirenzepine administration affects glycemic control. Nocturnal GH secretion was studied from 2300-0800 h before and after one month of pirenzepine administration (100 mg/day, orally, given at 2300 h) in 13 diabetic patients receiving their usual insulin treatment. GH secretion (GH area under curve) was blunted after pirenzepine administration [mean, 877 +/- 215 (+/- SE) vs. 1407 +/- 311 micrograms/L.min; P less than 0.002]. During pirenzepine administration, hemoglobin A1c significantly decreased (P less than 0.02), and 4 of the 13 patients had lower daily insulin requirements (5-23 U/day), but there was no significant change for the group as a whole. These results indicate that the inhibitory effect of pirenzepine on GH secretion persists when pirenzepine is given chronically and that pirenzepine seems to improve the metabolic control of the patients. PMID- 2918052 TI - The natural history of untreated hyperprolactinemia: a prospective analysis. AB - This report describes the results of a long term prospective study of 30 women with hyperprolactinemia who were not treated and who underwent yearly clinical, hormonal, and radiographic evaluation for an average of 5.2 yr (range 3-7 yr). At entry into the study 18 women had amenorrhea, 8 had oligomenorrhea, and 4 had regular menstrual periods. The initial mean serum PRL levels did not differ in women grouped according to menstrual function. Nine women (35%) had improvement in clinical symptoms. Serum PRL decreased, and menstrual periods normalized more often in those who initially had oligomenorrhea or regular menstrual periods. In most amenorrheic women serum PRL levels did not decline, and menstrual symptoms did not improve. Six of 30 women had an increase in serum PRL, 14 had no change, and 10 had a decrease, in 6 of whom serum PRL was normal at the last observation. Twenty-seven women had serial radiographic studies. Four (15%) of the 13 women with initially abnormal radiographic findings had normal studies later, 2 had tumor progression, and 7 no change. Four of 14 women who had normal radiographic studies initially developed radiographic evidence of a pituitary tumor, although the radiographic changes were minimal, and no patient developed a macroadenoma or pituitary hypofunction. Increases or decreases in serum PRL did not accurately predict changes in tumor size. Prior estrogen use and previous pregnancies did not increase the likelihood of tumor appearance or enhance tumor growth. The clinical presentation of the patient was an important factor in predicting which patients had a decline in serum PRL and resolution of symptoms. We conclude that patients with hyperprolactinemia are unlikely to have progression of their disease and may, in fact, have clinical and radiographic improvement. PMID- 2918053 TI - Augmentation of growth hormone secretion in children with constitutional growth delay by short term clonidine administration: a pulse amplitude-modulated phenomenon. AB - We evaluated the effect of chronic clonidine administration on 24-h integrated GH secretion (IC-GH) in eight children (six boys and two girls; age, 6.0-13.0 yr) with constitutional growth delay (CGD). Clonidine was given orally in a daily dose of 0.1 mg/m2 at bedtime for 6 months; 24-h secretion studies were performed before and after 2 months of treatment. Clonidine caused a significant augmentation (P less than 0.02) of mean IC-GH from 2.6 +/- 0.4 (+/- SE) to 4.6 +/ 0.6 micrograms/L. The increase in IC-GH was mainly the result of increased GH pulse amplitude, which rose from 12.3 +/- 1.3 to 18.2 +/- 2.1 micrograms/L (P less than 0.01). The mean GH pulse amplitude was significantly higher (P less than 0.02) during sleep (15.9 +/- 2.4 micrograms/L) than during the awake hours (8.4 +/- 1.5 micrograms/L) before treatment. During clonidine treatment the mean GH pulse amplitude during the awake hours (15.0 +/- 3.8 micrograms/L) was similar to that during sleep (20.3 +/- 3.1 micrograms/L). GH pulse frequency was not altered by treatment during either the awake or sleep hours. The mean insulin like growth factor I levels after 2 (1400 +/- 300 U/L) and 6 (1760 +/- 430 U/L) months of treatment were significantly higher (P less than 0.02 and P less than 0.05, respectively) than the pretreatment value (920 +/- 240 U/L). After 2 months of clonidine treatment, growth velocity increased from 3.1 +/- 0.5 to 10.2 +/- 1.0 cm/yr (P less than 0.001), and after 6 months of treatment is was still significantly higher (7.0 +/- 0.7 cm/yr; P less than 0.02) than that before treatment. These results confirm the ability of clonidine to accelerate growth in children with CGD and indicate that clonidine is capable of increasing IC-GH levels. They also reinforce the view that many children with CGD have decreased endogenous GH secretion. PMID- 2918055 TI - Variability in the quantitation of circulating growth hormone using commercial immunoassays. AB - The quantitation of human GH in a serum sample is not consistent among various commercially available immunoassays. We measured serum GH concentrations with four RIAs [Cambridge, Kallestad, National Hormone and Pituitary Program, and Radioassay Systems Laboratories (RSL)] and two immunoradiometric assays (IRMAs; Hybritech and Nichols). Serum GH concentrations measured by the RIAs were between 1.9 and 2.8 times higher than those determined by the Hybritech IRMA, whereas the concentrations measured by the Nichols IRMA were approximately 3.0 times higher than the Hybritech values. We evaluated the effects of differences in standards, assay diluents, and antibody specificity on GH measurement in the various assays. When GH standards from each of the assays were measured in the Hybritech IRMA, only the RSL standard was less immunoreactive than the other assay standards. Different assay diluents also resulted in varying GH values. In the RIAs, GH diluted in serum was more immunoreactive than GH diluted in phosphate-buffered saline-0.5% BSA. This enhanced immunoreactivity appeared to be due to a nonspecific effect generated by serum. The Nichols and Hybritech IRMAs provide standards diluted in horse serum. In the Nichols assay, GH diluted in human serum was more immunoreactive than GH diluted in horse serum, whereas the immunoreactivity of GH diluted in either serum was equal in the Hybritech IRMA. These IRMAs also differ in that the Nichols assay detected the 20K variant of GH, whereas the Hybritech assay did not. Considering these discrepancies, comparison of data obtained using different assays should be made carefully. PMID- 2918054 TI - Circulating immunoreactive oxytocin during the human menstrual cycle comes from the pituitary and is estradiol dependent. AB - The aims of this study were to 1) evaluate the relative contributions of hypothalamic and ovarian oxytocin (OT) to peripheral serum concentrations and 2) determine the relationship between serum OT and ovarian steroid concentrations. Four groups of women were studied: 1) women with spontaneous cycles (n = 4) and normal serum estradiol (E2), progesterone, LH, and FSH levels; 2) in vitro fertilization (IVF) patients (n = 8) undergoing ovarian hyperstimulation; 3) agonadal oocyte-recipient patients (n = 6) receiving replacement E2 and P therapy; and 4) postmenopausal women (n = 21). Peripheral serum samples were collected daily during a menstrual cycle from the normal and agonadal women and for 6 days before ovulation in the IVF group. Serum immunoreactive OT was measured by specific RIA after Sep-Pak extraction; the assay sensitivity was 0.6 pmol/L. Serum OT in the women with normal cycles increased during the follicular phase, reaching a peak 1 day after the LH surge, and decreased in the luteal phase [days 7, 16, and 21, 10.7 +/- 3.5 (mean +/- SE), 25.7 +/- 5.7, and 13.2 +/- 2.5 pmol/L, respectively; P less than 0.05]. Serum OT levels were higher in IVF patients before ovulation than in women with spontaneous cycles, but lower than those in the agonadal women, who had a peak value (49.1 +/- 9.6 pmol/L; P less than 0.05) on day 13 of E2/progesterone replacement therapy. Serum OT was positively correlated (r = 0.68, normal women; r = 0.91, oocyte recipients) with serum E2 values during the first part of the cycle (P less than 0.01). A similar positive correlation between serum OT and E2 was found in the postmenopausal women (r = 0.83). We conclude that serum OT before and around the time of ovulation comes mainly from the pituitary, and not from the ovary, and is E2 dependent. PMID- 2918056 TI - The nature of the defect in familial male pseudohermaphroditism in Arabs of Gaza. AB - Studies in six Arab individuals from Gaza with familial male pseudohermaphroditism (MPH) due to 17-ketoreductase deficiency revealed several metabolic aberrations associated with the disorder. Plasma LH, FSH, testosterone, and androstenedione concentrations were low in the two prepubertal patients. After hCG administration plasma androstenedione increased markedly. The four postpubertal MPH patients had very high plasma gonadotropin and androstenedione concentrations, the latter increasing further after hCG administration. Plasma testosterone concentrations in all six patients were moderately low or normal for age and increased little after hCG administration. Spermatic venous testosterone concentrations, measured in three adults, were within the normal range in two and low in one, while androstenedione concentrations were markedly elevated (15- to 32-fold) in all three patients. Kinetic analyses of progesterone and androstenedione metabolism were performed in testicular tissue of these patients and compared to the results in two control subjects. While testicular tissue from the two prepubertal patients metabolized progesterone only to androstenedione, and that to a limited extent, the tissue from the four postpubertal patients metabolized progesterone to 16 alpha- and 16 beta-hydroxyprogesterone, 17 alpha hydroxyprogesterone, androstenedione, and testosterone and metabolized androstenedione to testosterone. The Michaelis constants of these reactions were similar in the tissue from the MPH and the control subjects. The production of 16 alpha- plus 16 beta-hydroxyprogesterone was 5.4- to 10.3-fold greater, and 17 hydroxylase activity was 5.8- to 8.1-fold lower in the testes of the postpubertal MPH patients compared to values in the control subjects. The preference of androstenedione production through the delta 4- or delta 5-pathways was examined in the testes of two adult MPH patients using an equimolar concentration of [14C]progesterone and [3H]pregnenolone as substrates. While the flow of substrates in the control testes was equal or slightly greater through the delta 4-pathway, the delta 5-pathway predominated in the testes of the MPH patients. A large amount of dehydroepiandrosterone accumulated when NAD, the cofactor for 3 beta-hydroxysteroid dehydrogenase-isomerase, was omitted, supporting the contention that androstenedione was produced in the testes of the MPH patients mainly through the delta 5-pathway. Additional support for this suggestion was the finding that the 3H/14C ratio in androstenedione and testosterone produced from both substrates was 8 times higher in the testes from MPH patients than in those from the control subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918057 TI - Human corpus luteum: luteinizing hormone and chorionic gonadotropin receptors during the menstrual cycle. AB - To characterize and determine the concentration of LH/hCG receptors in human corpora lutea of the menstrual cycle, we measured occupied and unoccupied receptors and determined the association (Ka) and dissociation (Kd) constants individually in 23 corpora lutea (CL) and 4 corpora albicantia obtained at the time of tubal ligation from 25 normal cycling women. We found no [125I]hCG binding in any of the corpora albicantia. Scatchard plot analysis for each CL revealed a linear binding plot indicative of a single set of LH/hCG receptors. The mean concentration of unoccupied receptors was 36 +/- 10 (+/- SE) fmol/mg protein in the early luteal phase (days 15-19; n = 5), 64 +/- 11 fmol/mg protein in the midluteal phase (days 20-25; n = 13), and 42 +/- 19 fmol/mg protein in the late luteal phase (days 26-30; n = 5). The concentrations of occupied receptors were 56 +/- 8, 46 +/- 6, and 54 +/- 12 fmol/mg protein in the early, mid-, and late luteal phases, respectively. Total (occupied plus unoccupied) receptor concentrations reached maximum levels of 110 +/- 11 fmol/mg protein in the midluteal phase. Ka increased progressively from 12 +/- 4 X 10(9) mol/L-1 in the early luteal phase to 19 +/- 7 X 10(9) and 21 +/- 8 X 10(9) mol/L-1 in the mid- and late luteal phases. We conclude that in normal CL, 1) total and unoccupied LH/hCG receptor levels parallel progesterone secretion; 2) changes in the binding affinity may be important in sustaining and/or rescuing the CL; and 3) loss of LH/hCG receptors is probably related to luteolysis. PMID- 2918058 TI - Neurohypophyseal function in postpartum hypopituitarism: impaired plasma vasopressin response to osmotic stimuli. AB - We studied neurohypophyseal function in 12 women with postpartum hypopituitarism (Sheehan's syndrome) by measuring plasma arginine vasopressin concentrations during 5% hypertonic saline infusions. All patients had a history of obstetric shock or massive bleeding, and were receiving cortisol and/or L-T4 replacement therapy. None had any symptoms of diabetes insipidus. The mean basal plasma vasopressin level in the patients [0.6 +/- 0.1 (+/- SE) pmol/L] was significantly lower (P less than 0.01) than that in normal adults (2.5 +/- 0.5 pmol/L; n = 12), whereas mean plasma osmolality values were similar in the two groups. During hypertonic saline infusion, the 10 hypopituitary patients had varying degrees of subnormal arginine vasopressin responses to the increase in plasma osmolality. Urine-concentrating ability after dehydration also was lower in the patients, although overt polyuria was absent at the time of this study. These results indicate that the osmoregulation of arginine vasopressin secretion is frequently impaired in postpartum hypopituitarism, suggesting neurohypophyseal damage. PMID- 2918059 TI - Androgen resistance associated with a qualitative abnormality of the androgen receptor and responsive to high dose androgen therapy. AB - A 46,XY infant with perineoscrotal hypospadias and microphallus was identified in a family in which seven individuals have severe hypospadias that is inherited in a pattern compatible with an X-linked defect. The infant had small testes that were palpable in the labioscrotal folds, the proximal urethra was male in character, and there was no vagina. Serum testosterone rose from 0.5 to 5.1 nmol/L in response to hCG, and there was a negligible clinical response to a short term course of testosterone enanthate. A clinical diagnosis of male pseudohermaphroditism due to androgen resistance was made. Studies in cultured genital skin fibroblasts disclosed normal 5 alpha-reductase activity, a normal amount of high affinity dihydrotestosterone binding, and normal up-regulation of androgen receptors when monolayers were incubated with dihydrotestosterone or mibolerone. Fibroblast cytosol preparations contained a normal 7-8S sedimenting peak of androgen binding. However, androgen binding in monolayers decreased 60% when the assay temperature was raised from 30 to 41 C, and the dissociation rate of ligand from the receptor was enhanced 5-fold compared to the control value, establishing the diagnosis of androgen resistance due to a qualitative abnormality of the androgen receptor. Because of parental decision to raise the patient as a male, he was given two courses of high dose testosterone cypionate when he was 2.5 and 3.5 yr old (100 mg every 2 weeks for six doses). This treatment produced significant phallic growth, making it possible to undertake surgical correction of the hypospadias. We postulate that the impairment of androgen receptor function was overcome in part by the large dose of androgen. PMID- 2918060 TI - Human corpus luteum secretion of relaxin, oxytocin, and progesterone. AB - To determine whether the human corpus luteum is a source of relaxin and oxytocin, we measured the concentrations of these peptides in plasma obtained from the ovarian veins of ovaries with and without a corpus luteum and compared these to peripheral plasma levels. Peripheral and ovarian venous blood samples were obtained from 34 nonpregnant women, 13 during the luteal phase and 21 during the follicular phase of their cycles, and from a 6-week pregnant woman. Plasma relaxin, oxytocin, and progesterone concentrations were determined by sensitive and specific RIAs. Plasma relaxin levels were not detectable (less than 0.16 microgram/L) in peripheral or ovarian venous plasma not draining a corpus luteum. The mean relaxin concentration in plasma draining an ovary with a corpus luteum was 0.41 +/- 0.09 (+/- SE) microgram/L. Oxytocin levels also were significantly higher in plasma draining an ovary with a corpus luteum (6.70 +/- 1.86 pmol/L) than in that draining the ovary with no corpus luteum (1.58 +/- 0.09 pmol/L; P less than 0.01) or in peripheral plasma (1.58 +/- 0.09 pmol/L; P less than 0.025). The mean progesterone concentration also was highest in plasma draining an ovary with a corpus luteum (210.2 +/- 50.5 nmol/L) compared with those in plasma from the contralateral ovarian vein (40.3 +/- 16.5 nmol/L P less than 0.005) and peripheral plasma (30.2 +/- 5.7 nmol/L; P less than 0.005) during the luteal phase. In a woman who was 6 weeks pregnant, plasma draining the ovary with a corpus luteum had 1.9 micrograms relaxin/L, but only 0.49 pmol/L oxytocin; the latter was similar to concentrations in noncorpus luteum-bearing ovarian venous plasma. These findings indicate that the human corpus luteum secretes relaxin, oxytocin, and progesterone. Both ovarian oxytocin and relaxin may function as paracrine or autocrine modulators of luteal function. PMID- 2918061 TI - Lithium treatment increases intact and midregion parathyroid hormone and parathyroid volume. AB - Lithium carbonate is known to alter calcium metabolism by lowering urinary calcium excretion and increasing serum calcium concentrations. Several investigators have reported increases in serum immunoreactive PTH (iPTH) values after a few weeks or months of lithium treatment, and several cases of primary hyperparathyroidism developing during lithium treatment have been reported. To determine whether the increases in serum iPTH might be the result of increased renal retention of inactive PTH fragments rather than stimulation of parathyroid function, we measured plasma intact PTH by immunoradiometric assay and estimated parathyroid size by ultrasonography in men who had received short term (less than 6 months) or long term (greater than 3 yr) lithium treatment and in normal subjects. Serum ionized calcium was higher by 0.03-0.04 mmol/L in subjects treated short term (mean, 1.7 months) with lithium than in normal subjects, but plasma intact PTH and serum midregion iPTH values were not different. The absence of a reciprocal decrease in PTH values is compatible with a lithium-induced shift in the set-point for the inhibition of PTH secretion by calcium toward a higher calcium value. Both plasma intact PTH and serum midregion PTH values were higher in subjects during longer term (mean, 103 months) lithium treatment, and estimated parathyroid volume was 3-fold higher. Serum phosphate was lower, and serum chloride and plasma 1,25-dihydroxy-vitamin D values were higher in those treated with lithium long term, probably from the biological action of the increased PTH. We conclude that long term lithium treatment increases circulating biologically active PTH and causes parathyroid enlargement. Whether this chronic stimulus to parathyroid growth might lead to adenoma formation in certain susceptible individuals and whether a PTH-induced increase in skeletal remodelling occurs that might hasten the appearance of osteopenia remain to be determined. PMID- 2918062 TI - Plasma calcitonin levels are not lower than normal in osteoporotic women. AB - It has been suggested that postmenopausal osteoporosis is due to calcitonin deficiency. Interest in this concept has been increased because of the recent availability of nasal calcitonin for the management of osteoporosis. Plasma calcitonin and albumin-adjusted calcium levels were measured in 30 women with postmenopausal osteoporosis and 41 normal women matched for age and sex. Both mean plasma calcitonin and mean albumin-adjusted calcium levels were higher in the postmenopausal osteoporotic women [calcitonin, 21.0 +/- 17.6 (+/- SD) vs. 9.8 +/- 10.2 ng/L (P = 0.003); calcium, 2.33 +/- 0.09 vs. 2.27 +/- 0.07 mmol/L (P = 0.002)]. This result indicates that fasting calcitonin deficiency is not a feature of postmenopausal osteoporosis. PMID- 2918063 TI - The relationship between learning disability, emotional disorders, and neuropsychology; some results and observations. AB - Emotional disorders may precede learning disabilities, follow learning disabilities, or occur at the same time. This paper discusses evidence supporting each of these hypotheses, focussing on the possibility that both learning disabilities and emotional disorders, or at least some subforms of them, may have a common origin in neurological dysfunction. A model of interaction of the many factors involved in both the development and the persistence across age for both learning disabilities and emotional disorders is presented and avenues of research are discussed. Data from a 15-year follow-up study which illustrate some of these complex relationships are presented. PMID- 2918064 TI - Seventeenth annual INS meeting. International Neuropsychological Society. February 8-11, 1989, Vancouver, B.C., Canada. Abstracts. PMID- 2918065 TI - Levels of the antiprogestin RU 486 and its metabolites in human blood and follicular fluid following oral administration of a single dose. AB - Using high-pressure liquid chromatography (HPLC) the antiprogestin RU 486 and two of its metabolites (N-monodemethyl RU 486 and propargyl RU 486) were measured in plasma and follicular fluid of 21 women requesting laparoscopic sterilization. Pretreatment of the women involved ovulation induction with clomiphene and HCG. RU 486 (100 mg) was administered orally and 1 h later blood samples were withdrawn. Thirty-four hours later, at laparoscopy, samples of both blood and follicular fluid were collected. During the 34-h period the average plasma level of RU 486 decreased from 1.93 mumol/l to 0.91 mumol/l, i.e. by -50%. The latter concentration of RU 486 was not significantly different from that found in follicular fluid (0.79 mumol/l). The monodemethyl metabolite exhibited significantly higher plasma levels (3.09 mumol/l) than RU 486 1 h after administration. Thirty-four hours later these levels had decreased to 0.92 mumol/l, i.e. by 70%. In follicular fluid, the levels of the monodemethyl metabolite (1.76 mumol/l) were significantly higher than those of RU 486 (0.79 mumol/l). Because of background noise, only approximate values were established for the propargyl metabolite. These were 0.67 and 0.40 mumol/l, respectively, in plasma and 0.42 mumol/l in follicular fluid. The results indicate that RU 486 and two of its major metabolites can readily cross the blood-follicle barrier of human pre-ovulatory follicles. PMID- 2918066 TI - Serum levels of pregnancy-associated endometrial alpha 2-globulin (alpha 2-PEG) during normal menstrual and combined oral contraceptive cycles and relationship to immunohistological localization. AB - Serum levels of pregnancy-associated endometrial alpha 2-globulin (alpha 2-PEG), the major secretory protein of the endometrium during the late luteal phase of the menstrual cycle and early pregnancy, were measured serially during normal menstrual cycles and in women taking various combined oral contraceptives. Pill users were also sampled on an individual basis. Endometrium from women taking the combined oral contraceptive was examined immunohistochemically using a monoclonal antibody to alpha 2-PEG. Levels of alpha 2-PEG in the menstrual cycle sera showed consistent changes following the luteinizing hormone peak, with a greater than three-fold increase between basal levels at mid-cycle and those in the late luteal phase. Serum levels of alpha 2-PEG in the pill users remained at basal levels throughout the cycle, regardless of the progestagen in the formulation. This finding was noted in serial and individual samples from both monophasic and triphasic preparations. However, there was evidence of induction of alpha 2-PEG production at the local endometrial level when immunohistochemical staining was employed at various stages of the pill cycle. This suggests that serum levels of alpha 2-PEG may not necessarily reflect local endometrial production of the protein. These observations are discussed with reference to the proposed value of serum measurement of this protein in assessing relative progestagenic activity upon the endometrium. PMID- 2918067 TI - No increased histocompatibility antigen-sharing in couples with idiopathic habitual abortions. AB - Sharing of major histocompatibility antigens between spouses has been claimed to play an aetiological role in couples with unexplained, habitual spontaneous abortions. On the other hand there is evidence that a subset of habitually aborting women exists, in whom autoimmune aberrations seem to be of importance. In the present study, 56 couples with unexplained habitual abortions were histocompatibility typed for HLA-A, -B and -DR specificities, as were a group of 33 fertile control couples with two or more children and no spontaneous abortions. The DR-typing was done partly by use of the restriction fragment length polymorphism (RFLP). There was no significant difference in the distribution of histocompatibility antigens between the habitually aborting women and the control women. No increased HLA-antigen sharing could be demonstrated between spouses in aborting couples compared with controls, neither in each single locus nor in the combination of all loci (all P-values greater than 0.2). Neither could any increased HLA-antigen sharing in sub-groups of aborting couples with and without autoimmunity be demonstrated. It can be concluded from these data that compatibility between spouses for HLA-A, -B and DR-antigens per se only plays a minor role in the aetiology of habitual abortion. PMID- 2918068 TI - Recovery of motile sperm using the migration-sedimentation technique in an in vitro fertilization-embryo transfer programme. AB - Sperm washing techniques, based on the swim-up principle used before inseminating the human oocyte in in-vitro fertilization and embryo transfer programmes (IVF ET), usually require prior centrifugation which causes damage to the sperm cell. A technique is described for separating sperm at laboratory temperature based on sperm migration--sedimentation principles, using two concentric tubes and recovering 70-90% forward-moving cells. A group of 17 patients is presented who were managed with this method. The results were 85% fertilization rate, 4% polyspermia and six clinical pregnancies. PMID- 2918069 TI - A technical note on diluting semen for the haemocytometric determination of sperm concentration. AB - A comparison was made of the use of either an SMI positive displacement pipette or an Eppendorf Varipette as the method of sampling 63 liquefied semen samples for volumetric dilution and haemocytometry to determine sperm concentration. The 95% range of the differences between the values obtained using the SMI and the Varipette with whole tips was from -46.9 to 63.8 x 10(6)/ml. With the Varipette tips cut off 12.5 mm from the end the 95% range was from -52.4 to 55.8 x 10(6)/ml. Previous work had shown that the 95% ranges of differences between duplicate determinations using the SMI pipette were from -7.2 to 6.9 x 10(6)/ml for two 1 + 19 dilutions, or from -16.0 to 12.1 x 10(6)/ml for 1 + 19 and 1 + 49 parallel dilutions. Therefore, since the Varipette had a far greater potential for error, a positive displacement pipette should be used when taking precise volume aliquots of human semen. PMID- 2918070 TI - The role of follicular fluid in inducing the acrosome reaction of human spermatozoa incubated in vitro. AB - Motile human sperm populations were prepared from liquefied semen (5 donors x 3 replicates) using Percoll gradients at 30-60 min post-ejaculation and preincubated in a complex 'synthetic tubal fluid' culture medium (STF) at 37 degrees C under 5% CO2 in air for 6 h. Aliquots of these suspensions were then incubated for a further 2 h in STF containing 0, 5, 10, 25, 50, 75 and 100% (v/v) pooled human follicular fluid (FF). Another aliquot was treated with 10 micron A23187 in STF for 20 min and then incubated in fresh STF medium for a further 2 h to induce maximal acrosome loss. Acrosome reactions were assessed using both the triple-stain technique and fluorescent peanut agglutinin lectin-labelling. Sperm motility and movement characteristics were assessed from videorecordings using digital image analysis (CellSoft). Exposure to FF caused only relatively small proportions of the preincubated spermatozoa to undergo acrosome reactions. The size of these responsive sub-populations was smaller than that capable of responding to a Ca2+ influx generated by A23187. Increased FF concentrations induced a progressive loss of motility and trends for changes in movement characteristics that may have been related to reduced intracellular Ca2+. This interpretation of these observations is that while FF may act to stimulate or promote the human sperm acrosome reaction it does not appear to be a specific inducer of it. Consequently, a precise role for FF at the relatively low concentrations that would be expected to be present in the tubal ampulla in the physiological regulation of human fertilization remains unproven. PMID- 2918071 TI - Human fertilization by micro-injection of immotile spermatozoa. AB - Microfertilization of human oocytes with spermatozoa from a man with immotile cilia syndrome is reported, confirming a preliminary investigation where a zona free donor oocyte was fertilized with spermatozoa from the same patient. Oocytes from his spouse were obtained by laparoscopy after routine stimulation with clomiphene citrate, human menopausal and chorionic gonadotrophins, and were cultured for 4-6 h in Whittingham's T6 medium, supplemented with 10% of her serum. The spermatozoa were washed and processed in the same medium and capacitated for 6-8 h before micromanipulation. Three of five mature oocytes were fertilized by micro-injection of a single immotile spermatozoon into the perivitelline space. One oocyte produced a two-pronuclear ovum assessed 19 h after injection, while the other two produced 2-cell embryos with blastomeres of equal size, 22 h after injection. These embryos cleaved to 3-8-cell stages in culture before embryo replacement. No pregnancy resulted from embryo transfer. The results conclusively demonstrate that human oocytes can be fertilized successfully with immotile spermatozoa by micro-injection and the work has profound implications in the treatment of severe male infertility. PMID- 2918072 TI - Effect of damage to the zona pellucida on development of preimplantation embryos in the mouse. AB - The effect on development of early mouse embryos of making a hair-line slit in the zona pellucida of approximately one-third its diameter was investigated. The rate of development to mid-gestation of operated zygotes and 2-cell embryos transferred directly to the oviduct was significantly lower than that of sham operated or unoperated controls. However, the operation had no discernible effect on the development of 2-cell embryos that were cultured for 2 days prior to transfer to the uterus, or on embryos composed of 8 or more cells transferred directly to the oviduct. Zona slit zygotes and 2-cell embryos exhibited a significantly higher rate of anomalous development to the morula or blastocyst stage than controls following short-term transfer to the adult or immature oviduct. Such anomalies could not be attributed to damage of the embryos by leucocytes or bacteria entering through the wound in the zona. Rather, the typically non-spherical shape of slit zonae, together with the fact that some were empty on recovery, was consistent with operated embryos having been damaged by compression during passage through the oviduct. This suggests that, providing it is intact, the zona pellucida protects the early embryo from contraction of the oviductal musculature which is sufficient to lyse, arrest or extrude blastomeres prior to the formation of intercellular junctions. Hence, in experimental manipulations entailing damage to the zonae of early embryos, there may be a case for allowing them to form morulae in vitro prior to transfer, rather than returning them directly to the oviduct. PMID- 2918073 TI - Non-invasive measurement of glucose and pyruvate uptake by individual human oocytes and preimplantation embryos. AB - Pyruvate and glucose uptake by 73 individual human oocytes and preimplantation embryos was measured non-invasively, using an ultramicrofluorescence assay to analyse changes in substrate levels in microdroplets of culture medium. The uptake of both substrates was measured over successive daily incubations between days 1 (unfertilized oocytes) or 2 ('spare' embryos which were not transferred) and day 6 (day 0 = day of insemination). Under these conditions, 58% (25/43) of fertilized embryos with two pronuclei on day 1 developed to the blastocyst stage by day 6. The pyruvate uptake of these embryos increased from approximately 28 to a maximum of 40 pmol/embryo/h between days 2.5 and 4.5. Similarly, glucose uptake increased from approximately 8 to 14 pmol/embryo/h between days 2.5 and 4.5, but then increased further to 24 pmol/embryo/h on day 5 at the blastocyst stage. [corrected] The pyruvate uptake of fertilized embryos which arrested at cleavage stages was significantly lower than for those which developed to the blastocyst stage. Polyspermic and parthenogenetic embryos, and unfertilized oocytes also had lower pyruvate uptakes at later stages. The glucose uptake of unfertilized oocytes and abnormal embryos never reached the level of fertilized embryos at the blastocyst stage on day 5.5. Non-invasive measurement of pyruvate uptake before embryo transfer may provide a valuable functional criterion for the selection of viable embryos capable of developing to the blastocyst stage. PMID- 2918074 TI - Efficacy of the antiprogestin mifepristone (RU 486) prior to prostaglandin termination of pregnancy. AB - Forty-nine patients undergoing mid-trimester extra-amniotic prostaglandin termination of pregnancy were studied. Twenty patients acted as controls and received the standard hospital regime. Twenty-nine patients received the same regime, but in addition were given a single 200-mg oral dose of the antiprogesterone, mifepristone (RU 486), 24 h prior to prostaglandin infusion. The dose of prostaglandin required and the induction to abortion interval in the mifepristone-pretreatment group was significantly reduced. Complication rates were similar in both groups. Mifepristone is a safe and useful adjuvant therapy in mid-trimester prostaglandin termination. PMID- 2918075 TI - Discussion on ethical and judicial aspects of embryo research. PMID- 2918076 TI - Methysergide, a serotonin antagonist, does not inhibit the expression of autoimmune encephalomyelitis in the rabbit. AB - In view of recent interest in the potential role of vasoactive amines in the expression of experimental autoimmune encephalomyelitis (EAE) and neuritis (EAN), we set out to determine the effect of slow-release methysergide, a serotonin antagonist, on the effector phase of EAE/EAN in rabbits immunized with homologous spinal cord in Freund's adjuvant. On day 6 post-immunization (p.i.), slow-release pellets of methysergide maleate were implanted subcutaneously in graded doses 0 400 mg. At the highest dose, blood concentrations of methysergide were approximately 90 ng/ml on day 8 p.i. falling to 20 ng/ml by day 16 p.i. However, even at the highest dose of methysergide, rabbits developed typical clinical and histological signs of EAE/EAN. It is concluded that serotonergic mechanisms do not play a critical role in the effector phase of EAE/EAN in the rabbit. PMID- 2918077 TI - Glycine-immunoreactive projection of the cat lateral superior olive: possible role in midbrain ear dominance. AB - Neurons in the lateral superior olive are optimally excited by stimulation of the ipsilateral ear, as are those in the inferior colliculus by stimulation of the contralateral ear. This reversal of ear dominance may result, in part, from distinct crossed excitatory and uncrossed inhibitory pathways ascending from the lateral superior olive. To explore this possibility, immunoreactivity for two putative inhibitory neurotransmitters, glycine and GABA, was examined in projection neurons that retrogradely transported horseradish peroxidase from the cat inferior colliculus. The results suggest that the projection from the lateral superior olive can be segregated, immunocytochemically, into three components: 1) a crossed, glycine-negative (-) projection; 2) an uncrossed, glycine-positive (+) projection; and 3) an uncrossed, glycine(-) projection. Additional evidence suggests that the terminal fields of the two uncrossed projections may distribute differently within the inferior colliculus. Glycine(+) or glycine(-) projection neurons, crossed or uncrossed, do not differ in the size, shape, or location of their somata. However, most glycine(-) neurons are heavily encrusted with glycine(+) endings; glycine(+) neurons have 40-60% fewer of these endings. Glycine(-) neurons located in the lateral limb have fewer glycine (+) perisomatic endings than those in the medial limb. Few projection neurons are GABA(+), and GABA(+) perisomatic endings are rare in the lateral superior olive. Thus, there is a heavy uncrossed projection from the cat lateral superior olive to the inferior colliculus that may be glycinergic and inhibitory. Furthermore, there is a bilateral projection that is not glycinergic or GABAergic, which may be excitatory. The potential contribution of these pathways to contralateral ear dominance in the inferior colliculus is discussed. PMID- 2918078 TI - Forebrain projections from cholecystokininlike-immunoreactive neurons in the rat midbrain. AB - The purpose of the present study was to analyze the distribution of cholecystokininlike-immunoreactive (CCK-I) neurons within the rat ventral mesencephalon which project to several forebrain areas. The peroxidase antiperoxidase immunocytochemical technique was used to examine the anatomical localization of CCK-I within the ventral midbrain and in the following forebrain regions: caudate-putamen, nucleus accumbens, olfactory tubercle, bed nucleus of the stria terminalis, septum, amygdala, and prefrontal, anterior cingulate, and piriform cortices. CCK-I perikarya were distributed throughout the substantia nigra, ventral tegmental area, and several midline raphe nuclei to a greater extent than previously reported, particularly in the substantia nigra pars compacta. Terminallike immunoreactivity for CCK was observed in all of the above forebrain sites. In addition, infrequent CCK-I cell bodies were localized in the caudate-putamen, nucleus accumbens, olfactory tubercle, septum, and bed nucleus of the stria terminalis. To analyze forebrain projections of the ventral midbrain CCK-I neurons, indirect immunofluorescence was combined with fluorescence retrograde tracing. CCK-I neurons of the substantia nigra and/or ventral tegmental area were found to project, to varying extents, to all of the above CCK I forebrain terminal fields. The nucleus accumbens, olfactory tubercle, and septal and prefrontal cortical projections arose primarily from CCK-I perikarya in the ventral tegmental area whereas the projections to the caudate-putamen and anterior cingulate cortex arose predominantly from immunoreactive neurons in the substantia nigra pars compacta. The amygdala received innervation mainly from CCK I cell bodies located in the substantia nigra pars lateralis. CCK-I afferents to the bed nucleus of the stria terminalis and piriform cortex originated from perikarya distributed approximately equally across the ventral tegmental area and substantia nigra pars compacta. The general topography of CCK-I forebrain innervation observed in this study is similar to that previously reported for the ascending dopaminergic projections from ventral mesencephalic neurons. CCK-I neurons of the midline raphe nuclei were found to provide relatively minor afferents to the caudate-putamen, bed nucleus of the stria terminalis, septum, and prefrontal cortex and more substantial projections to the amygdala. The results of this study demonstrate that CCK-I neurons of the ventral midbrain supply a much broader innervation of forebrain regions than previously appreciated.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2918079 TI - Evidence for an alteration of the tonotopic map in the gerbil cochlea during development. AB - We have investigated developmental alterations in the tonotopic projection of the gerbil lateral superior olive. Single neurons were characterized in the frequency domain and the recording site marked with fast green. Transverse tissue sections from the auditory brainstem of each animal were visualized with a video-equipped microscope, and the image was digitized for subsequent alignment. The three dimensional display indicated little variation in the rostrocaudal axis, allowing us to collapse the data into a two-dimensional tonotopic map. The tonotopic map was found to change with age such that the characteristic frequency of neurons in a given anatomical location became successively higher during development. These results are consistent with the hypothesis that the place code gradually shifts in the developing cochlea. PMID- 2918080 TI - Comparative distribution of three opioid systems in the lower brainstem of the monkey (Macaca fuscata). AB - The regional distribution of the three opioid peptide neuronal systems- proopiomelanocortin (POMC), proenkephalin A, and proenkephalin B--was investigated in the lower brainstem of Japanese monkeys (Macaca fuscata) by immunocytochemical techniques. Antiserum to beta-endorphin/beta-lipotropin, [Met] enkephalin-Arg6-Gly7-Leu8, and human leumorphin were used to identify the POMC and the proenkephalin A and B systems, respectively. POMC-related immunoreactive material was not found in the neuronal perikarya in the lower brainstem; reactive fibers and apparent terminals were distributed in the substantia nigra, lemniscus lateralis, midbrain central gray, the nucleus raphes, nucleus parabrachialis lateralis, ventral area of the spinal trigeminal nerve, nucleus tractus solitarii, and in the reticular formation throughout the lower brainstem. Proenkephalin A-related immunoreactive neuronal perikarya were detected in the central gray, reticular formation, nucleus raphes, trapezoid body, nucleus parabrachialis lateralis and medialis, nucleus spinalis nervi trigemini, nucleus dorsalis nervi vagi, and in the nucleus tractus solitarii. Densely packed immunoreactive fibers were widely distributed in the substantia nigra, nucleus interpeduncularis, nucleus raphes, superior colliculus, periaqueductal central gray, nucleus parabrachialis lateralis and medialis, locus coeruleus, trapezoid body, nuclei cochleares, nucleus spinalis nervi trigemini, tractus spinalis nervi trigemini, nucleus tractus solitarii, nucleus dorsalis nervi vagi, nucleus gracilis, nucleus cuneatus, nucleus cuneatus accessorius, and in the reticular formation throughout the lower brainstem. Neuronal perikarya containing immunoreactive material related to proenkephalin B were found in the periaqueductal central gray, nucleus parabrachialis lateralis and medialis, nucleus tractus solitarii, and nucleus spinalis nervi trigemini. In addition, immunoreactive fibers were detected in the ventral tegmental area, substantia nigra, nucleus parabrachialis lateralis and medialis, nucleus vestibularis lateralis and medialis, and in some areas of the reticular formation. These anatomical findings demonstrate that these three opioid peptide neuronal systems are widely but uniquely distributed in the lower brainstem of the monkey. PMID- 2918081 TI - Topographical organization of the projections from the reticular thalamic nucleus to the intralaminar and medial thalamic nuclei in the cat. AB - The topography of the projections from the reticular nucleus of the thalamus (RT) to the intralaminar and medial thalamic nuclei were studied in the cat by the method of retrograde transport of horseradish peroxidase (HRP). Single small injections of the enzyme were made in the different intralaminar nuclei- mediodorsal, ventromedial, midline, and habenular--and in anterior group nuclei. The location and density of the neuronal labeling in the different parts of the RT were studied in each case. Our results show that 1) after injections located in all the nuclei here studied, a consistent number of labeled neurons were found in the RT, except for the injections in the lateral habenula and the anterior thalamic nuclear complex, both of which did not label neurons in the RT. 2) Among the other thalamic nuclei here studied, the most medially situated receive less numerous RT projections than those most laterally located. 3) Injections in all the nuclei studied gave rise to a cellular labeling in the anterior sectors of the RT, except for the anterior nuclear group and the lateral habenula. The projections from the rostral pole of the RT were topographically mediolaterally organized. 4) The anterodorsal part of the pregeniculate sector of the RT projects upon the large-celled part of the lateral central nucleus and to a lesser extent upon the paracentral, centromedian, and ventromedial nuclei, the anterior part of the lateral central nucleus, and the lateral band of the mediodorsal nucleus. The posterodorsal part of the RT pregeniculate sector only projects to the large-celled part of the lateral central nucleus. The dorsal portion of the posteroventral part of the RT pregeniculate sector also projects upon the large-celled part of the lateral central nucleus; its ventral portion projects to the ventromedial nucleus, the posterior part of the paracentral nucleus, the lateral band of the mediodorsal nucleus, and the centromedian nucleus. 5) The infrageniculate sector of the RT projects to the posterior part of the ventromedial nucleus. A weaker projection to the large-celled part of the lateral central nucleus, the centromedian nucleus, and the lateral band of the mediodorsal nucleus was also observed. 6) The ventral lateral geniculate nucleus projects upon the large-celled part of the lateral central nucleus, the lateral band of the mediodorsal nucleus, and the ventromedial nucleus. All these findings suggest an important modulatory action of the RT on the activity of the thalamic nuclei considered here. PMID- 2918082 TI - Organization and synaptic interconnections of GABAergic and cholinergic elements in the rat amygdaloid nuclei: single- and double-immunolabeling studies. AB - The aim of this study was to describe the localization of cholinergic and GABAergic neurons and terminals in the amygdaloid nuclei of the rat. Double immunolabeling was performed to study cholinergic-GABAergic synaptic interconnections. Cholinergic elements were labeled by using a monoclonal antibody to choline acetyltransferase (ChAT), the acetylcholine synthesizing enzyme. Antibodies against glutamate decarboxylase (GAD), the GABA- synthesizing enzyme, were employed to identify GABAergic perikarya and terminals. The tissue sites of the antibody bindings were detected by using either Sternberger's peroxidase-antiperoxidase (PAP) method or a biotinylated secondary antibody and avidinated ferritin. These two contrasting immunolabels allowed us to study GABAergic-cholinergic interconnections at the electron microscopic level. Our study revealed a characteristic distribution of GABAergic and cholinergic elements in the various amygdaloid nuclei: 1) Large, ChAT-immunopositive cells with heavily labeled dendrites were observed in the anterior amygdaloid area and in the lateral and medial zones of the central nucleus. These cells seem to constitute the intraamygdaloid extension of the magnocellular basal nucleus. Their dendrites invaded other amygdaloid nuclei, in particular the intercalated nuclei, the lateral olfactory tract nucleus, and the central zone of the central nucleus. These ChAT-immunoreactive dendrites formed synaptic contacts with GAD positive terminals. GABAergic terminals probably thus exert an inhibitory amygdaloid influence onto cholinergic neurons of the magnocellular basal nucleus. 2) Two amygdaloid nuclei-the basal dorsal nucleus and the lateral olfactory tract nucleus-contained a dense network of ChAT-immunoreactive fibers and terminals, but they also contained numerous GAD-positive perikarya. Double-immunolabeling experiments revealed cholinergic terminals forming synaptic contacts on GAD immunopositive cell bodies, dendritic shafts, and spines. 3) The central and medial nucleus seem to be the main target of GABAergic fibers to the amygdala. Both nuclei contained a dense plexus of GAD-immunoreactive terminals that may arise, at least in part, from the GABAergic neurons in the basal dorsal nucleus. Inhibition of the centromedial "excitatory" region through intraamygdaloid GABAergic connections may reduce excitatory amygdaloid influence onto hypothalamus and brainstem. PMID- 2918083 TI - Target dependence of hypoglossal motor neurons during development in maturity. AB - We have investigated the target dependence of hypoglossal motor neurons in postnatal rats by transecting the hypoglossal nerve and preventing reinnervation of the tongue. After transection in early postnatal life, approximately 60% of hypoglossal motor neurons die and surviving neurons are markedly atrophic compared to contralateral controls. In maturity, there is also substantial neuronal atrophy and about 30% of motor neurons appear to die after the procedure. However, most hypoglossal neurons in adults survive transection for periods up to 1 year. The adult response is present by 3 weeks of age. The time course of neuronal atrophy and death after permanent target deprivation was investigated in adult animals. One month after the hypoglossal nerve was deflected, there was marked axonal atrophy, although somatic atrophy was minimal. By 3 months after the procedure substantial neuronal atrophy and apparent cell loss (about 30%) had occurred. There was little change between 3 and 6 months. We conclude that hypoglossal motor neurons are influenced by connections with their targets in postnatal life. Even in maturity, neurons require target connections for maintenance of axonal and somatic morphology. However, the majority of motor neurons in adult animals can survive target deprivation for prolonged periods. PMID- 2918084 TI - Sensory pathways and motoneurons of the proboscis reflex in the suboesophageal ganglion of the honey bee. AB - A morphological description is given for the motoneurons underlying the proboscis extension reflex in the honey bee (Apis mellifera). Sensory neurons from the mandibles and labium were examined and their projection areas were related to those of the motoneurons. Motoneurons are located in the ventral part of the suboesophageal ganglion, have their somata in the hemiganglion ipsilateral to the filled nerve, and send prominent branches through identified ventral commissures into the contralateral hemiganglion. Motoneurons to the same muscle have parallel running projections into the contralateral hemiganglion, often parallel-running neurites and show vast areas of dendritic overlap. Arborizations of motoneurons are not restricted to their neuromere of origin but invade adjacent neuromeres, resulting in regions of dendritic overlap of motoneurons to different muscles. Sensory fibers from the mouthparts terminate in medio- and mediolateral parts of the suboesophageal ganglion, where their arborizations overlap with projections from motoneurons. A few sensory fibers descend in ventral parts of the cervical connective. Although sensory neurons from the mandible are restricted to the ipsilateral hemiganglion, those of the labium also show contralateral branches. These observations are discussed in the context of the suboesophageal ganglion as a ganglion composed of the embryonic fusion of three single neuromeres. PMID- 2918085 TI - Regional specialisation for synaptic input and output on a locust intersegmental interneurone with multiple spike-initiating zones. AB - A4I1 is a long intersegmental interneurone whose soma lies in the fourth abdominal ganglion and whose axon ascends through, and branches in, the thoracic and suboesophageal ganglia and the brain. It receives sensory input in the prothoracic ganglion from wind-sensitive hairs on the head and prosternum and in the fourth abdominal ganglion from cercal afferents (Pfluger: J. Comp. Neurol. 222:343-357, '84). Spikes can be initiated from both of these ganglia. In the present study the neurone was stained by intracellular injection of cobalt salts for light microscopy and of horseradish peroxidase for electron microscopy. The morphology of its neurites in the thoracic and fourth abdominal ganglia and the distribution of synapses upon them could then be observed and correlated. In the fourth abdominal ganglion the neurone receives input synapses but makes no outputs. In each thoracic ganglion the neurone has fine, varicose ventral neurites and thicker dorsal neurites. The ventral neurites are most abundant in the prothoracic ganglion where they receive only input synapses. In the meso- and metathoracic ganglia the ventral neurites also receive inputs, but in addition they make output synapses. In all three thoracic ganglia output synapses are abundant on the dorsal branches, but in the meso- and metathoracic ganglia a small number of inputs are also received here. The possibility that the function of the interneurone may not be the same in all of the thoracic ganglia is discussed in the light of its known physiological properties. PMID- 2918086 TI - Purkinje cell reduction in the reeler mutant mouse: a quantitative immunohistochemical study. AB - We have used the immunohistochemical detection of the Purkinje cell marker cGMP dependent protein kinase to identify Purkinje neurons in the cerebellum of the reeler mutant mouse. Our quantitative analysis of Purkinje cell number based on this marker indicates that reeler mice possess approximately 82,000 Purkinje cells, slightly less than half the number found in normal mice. Our analysis also shows that 5% of the Purkinje cells in reeler are located in a normal position (between molecular and granular layers), 10% are found in the granular layer, and the remainder form the deep cellular masses characteristic of the reeler cerebellum. The finding of a major Purkinje cell deficit in reeler was surprising in that most investigators consider this mutation to effect cell migration as opposed to cell number. Although we cannot determine whether the Purkinje cell loss in reeler is a primary or secondary gene effect, the possibility that the reeler gene has its effect on migration through a primary effect on neurogenesis or cell survival should be considered. PMID- 2918087 TI - Development of central projections of lumbosacral sensory neurons in the chick. AB - The development of central projections of sensory neurons in lumbosacral dorsal root ganglia (DRGs) was examined by using horseradish peroxidase labeling techniques in chick embryos from stage 23 (E4) to stage 39 (E13). Our results show that primary afferents reach the spinal cord by stage 23. Afferent axons extend in the primordium of the dorsal funiculus for several segments rostral and caudal to their segment of entry for over 24 hours before invading the gray matter at stage 28 (E6). Sensory fibers grow into the vicinity of motoneuron dendrites by stage 32 (E7.5), about the time that reflexes and apparent monosynaptic EPSPs can first be elicited. Dense projections into the dorsal laminae of the spinal cord, presumably representing cutaneous afferents, appear somewhat later, at about stage 39 (E13), when the segmental projection pattern begins to resemble the mature pattern. PMID- 2918088 TI - Development of the peripheral trigeminal system in the chick revealed by an isotype-specific anti-beta-tubulin monoclonal antibody. AB - Using a monoclonal antibody directed against a class III beta-tubulin isotype, c beta 4, we studied the time course of the expression of this protein, the morphological differentiation of the immunoreactive cells, and the time course of peripheral axon outgrowth in the chick trigeminal (V) system. The neural crest precursors of the V ganglion neurons do not express the antigen until they begin to differentiate as neurons. The placodal precursors of the V ganglion neurons express the antigen while they still are cuboidal epithelial cells. They continue to be immunoreactive as they migrate from the placode and settle in the ganglion, prior to sprouting axons. The V motoneurons express the antigen near the time of their terminal mitotic division. Using this antibody to visualize axons, we demonstrate that both ganglionic and motoneuron axons grow out as individual fibers, much like pioneer axons. Both halt their extension for several hours once they attain the vicinity of their targets. During this pause many other axons join the nerve bundles. Finally, single pioneer axons split from the main trunk to begin local target innervation. PMID- 2918089 TI - Connections of the olfactory bulb and nucleus olfactorius anterior in the hedgehog (Erinaceus europaeus): fluorescent tracers and HRP study. AB - The projections of the main olfactory bulbs (MOBs) and the dorsal part of the anterior olfactory nucleus (NOA) in the hedgehog (Erinaceus europaeus) have been studied by fluorescent tracers and the horseradish peroxidase method (HRP), respectively, to reveal the pattern of labeling from these structures. After different dye injections in both MOBs, labeled cells were present in the following structures: tenia tecta, vertical limb of the diagonal band of Broca, and medial septal nucleus in the ipsilateral injection site; and the NOA, piriform cortex, nucleus of the lateral olfactory tract, horizontal limb of the diagonal band of Broca, posterolateral cortical amygdaloid nucleus, anterior amygdaloid area, and dorsal raphe nucleus in both hemispheres. Structures showing double-labeled cells were the NOA, horizontal limb of the diagonal band of Broca, nucleus of the lateral olfactory tract, anterior amygdaloid area, and posterolateral cortical amygdaloid nucleus. After HRP injections in the dorsal part of the NOA, labeled cells were distributed in the NOA, nucleus of the lateral olfactory tract, posterolateral cortical amygdaloid nucleus, piriform cortex, horizontal and vertical limbs of the diagonal band of Broca, mitral cell layer of the MOB, tenia tecta, anterior amygdaloid area, and the contralateral NOA. We suggest that the contralateral projection nuclei to the MOB of the hedgehog, unusual in other mammals, and the large number of cells with axonal collaterals projecting to both hemispheres, may be a strategy in these animals to bilaterally integrate brain functions at the expense of its reduced corpus callosum. PMID- 2918090 TI - Ultrastructural localization of immunoreactive calbindin-D28k in the rat and monkey basal ganglia, including subcellular distribution with colloidal gold labeling. AB - Normal cellular function depends on the controlled flux of Ca++ within intracellular compartments and across the plasma membrane. Proteins that bind Ca++ are thought to contribute to the regulation of intracellular Ca++ and, perhaps more importantly, signal functional changes in cell activity. In the brain, calbindin-D28k is among a class of calcium-binding proteins that are widely and heterogeneously distributed in select populations of neurons, among them neostriatal cells, but whose function is largely unknown. In this study of the monkey and rat neostriatum and globus pallidus, calbindin-D28k was localized with immunoperoxidase and immunogold methods in order to identify striatal cell populations that contain this protein and the subcellular compartments in which it is likely to function. Light and electron microscopy showed intense and extensive labeling of immunoreactive calbindin-D28k in the cell bodies, dendrites, and spines of medium-sized neostriatal spiny neurons and in their axon terminals which end in the globus pallidus. More discrete labeling with a gold conjugated second antibody showed that the predominant site of calbindin-D28k was the matrix of the cytoplasm. Gold label was also associated with the karyoplasm of spiny cells and with the neurofilaments and axoplasmic matrix of striatopallidal axons and terminals, respectively. Membranes were either sparsely labeled (endoplasmic reticulum, mitochondria) or devoid of gold particles (nuclear envelope and plasmalemma). Radioimmunoassays of striatal subcellular fractions supported the anatomical findings by indicating that the soluble fractions of neostriatal tissue homogenates contained most of the calbindin-D28k immunoreactivity and that washes from forebrain synaptosomes treated with Triton X-100 yielded high levels of immunoreactive calbindin-D28k. These findings show that immunoreactive calbindin-D28k is localized to spiny neurons of the striatopallidal pathway and are consistent with previous observations on subcellular localization in nonneuronal tissues. If, as recently speculated, calbindin-D28k regulates calcium concentrations in neostriatal spiny neurons, this feature may be particularly involved with the high density of glutamatergic inputs to these cells. More work is needed to determine whether calbindin-D28k, when complexed to Ca++ in neostriatal spiny cells, signals the activation of protein kinases, phosphorylation, and/or neurotransmitter release, as has been shown for other Ca++-binding proteins in mammalian tissues. PMID- 2918091 TI - In situ localization of myosin and actin in dendritic spines with the immunogold technique. AB - The in situ detection of macromolecules by means of immunoelectron microscopy provides information about their ultrastructural localization in cellular compartments. With this technique, we have demonstrated that the contractile proteins actin and myosin are both localized in dendritic spines at densities exceeding those of other neuronal compartments. Myosin was associated with actin filaments, with spine plasma membrane, and with membranes of the spine apparatus. Given the dynamic properties of actin and myosin, these data suggest that these proteins may be involved in the mechanism of synaptic plasticity in general and in morphometric change resulting from intense synaptic activation in particular. PMID- 2918092 TI - Postembryonic development of serotoninlike immunoreactivity in the central nervous system of the snail, Lymnaea stagnalis. AB - Posthatching growth in the pond snail Lymnaea stagnalis involves approximately a 20-fold increase in the linear dimensions of the ganglia composing the central nervous system. Developmental change within the population of neurons exhibiting serotoninlike immunoreactivity (SLIR) was examined in order to explain this growth in cellular terms. The study indicates that at least two factors contribute to the growth of the nervous system. First, SLIR cells approximately double in number from the 200-250 cells in hatchlings to the complement found in animals approaching sexual maturity. Much of this increase in cell number occurred within identifiable discrete clusters of neurons with different clusters adding cells at different rates and at different times. The number of SLIR cells also increased in more diffuse populations, particularly along the medial aspects of the paired pedal and the right parietal ganglion. No identified cells were added postembryonically. In addition to the increases in neuron numbers, posthatching development in Lymnaea also involves the growth of individual cells. All cells examined showed continuous somatic growth during posthatching development, but different identified cells and different cell clusters were characterized by different rates of relative growth. Together, the results highlight the complexity of postembryonic development in the snail by indicating the temporal and spatial specificity for both cell addition and cell growth within the nervous system. PMID- 2918093 TI - Descending projections from auditory brainstem nuclei to the cochlea and cochlear nucleus of the guinea pig. AB - Projections from auditory brainstem nuclei to the cochlea and cochlear nuclei in the guinea pig were studied by injection of two retrograde fluorescent neuronal tracers. For seven experiments fast blue was injected into the scala tympani of one cochlea and diamidino yellow was injected into dorsal or anteroventral cochlear nucleus of the same side. The results show that the efferent projections to the cochlea and cochlear nucleus generally form two separate neuronal systems even though they share many common nuclei of origin. The largest projections to the cochlear nucleus come bilaterally from the lateral and ventral nuclei of the trapezoid body. Other nuclei, the lateral superior olive, the ventral nucleus of the lateral lemniscus, the dorsomedial periolivary nuclei, and the medial nucleus of the trapezoid body showed an ipsilateral bias in their projections to the cochlear nucleus. An upper limit of 3.5% of the medial system olivocochlear efferent neurones projecting to the cochlea were labelled with both diamidino yellow and fast blue, suggesting that few efferent neurones projecting to the cochlea send collaterals to the cochlear nucleus in this species. However, the site of medial system olivocochlear efferent collateral terminations is the granule cell area for the cat, mouse, and gerbil. When diamidino yellow was injected in the superficial layers of the cochlear nucleus, including the superficial granule cell layer of the ventral cochlear nucleus, approximately 3.6% of medial system olivocochlear efferents projecting to the cochlea sent collaterals to the cochlear nucleus. In three animals fast blue was injected into the cochlear nucleus and diamidino yellow into the cochlea. These experiments revealed a greater proportion of the medial system olivocochlear efferents projecting to the cochlea sending collaterals to the cochlear nucleus, but this proportion was still less than 10%. These results were confirmed by the extracellular injection of horseradish peroxidase into the intraganglionic spiral bundle. Only three medial system olivocochlear efferents were observed to send collaterals to the cochlear nucleus. This number was less than 10% of all labelled medial system fibres. Although these experiments suggest that in the guinea pig the number of olivocochlear efferents sending collaterals to the cochlear nucleus is considerably smaller than is found for the cat, mouse, and gerbil, it is not possible with the current experimental procedures to conclude whether the results are due to species or methodological differences. PMID- 2918094 TI - Quantitative autoradiographic mapping of serotonin 5-HT1 and 5-HT2 receptors and uptake sites in the neocortex of the rhesus monkey. AB - The in vitro autoradiographic technique was used to characterize the distribution of serotonin 5-HT1 and 5-HT2 receptors and uptake sites in 11 cortical areas of frontal, parietal, and occipital lobes in the rhesus monkey; 5-HT1 receptors were labeled with [3H]5-HT; 5-HT2 receptors were labeled with [3H]ketanserin; and 5-HT uptake sites were labeled with [3H]citalopram. Five-HT1 and 5-HT2 receptors and 5 HT uptake sites were found in every cortical area examined with the absolute concentration of 5-HT1 receptors higher than that of 5-HT2 receptors in all areas. In eight regions of prefrontal and parietal as well as in prestriate cortex, 5-HT1 and 5-HT2 receptors had complementary distribution profiles: 5-HT1 receptors were concentrated in layers I and II and the upper strata of layer III, while 5-HT2 receptors had their highest concentration throughout layers III and IV. Only the primary motor and visual cortex had receptor distributions different from that described above. Thus, in the primary visual cortex, both 5-HT1 and 5 HT2 receptors were found in high concentration in sublayer IVc beta, though the density of 5-HT1 receptor was also high in other subdivisions of layer IV and in layers III, V, and VI. In the primary motor cortex, both receptor subtypes were concentrated in layers I and II and the upper strata of layer III. The pattern of distribution of serotonin uptake sites did not match the patterns of distribution of either 5-HT1 or 5-HT2 receptors alone; rather it approximated the combined patterns of distribution of both receptor subtypes. The complementary patterns of distribution of 5-HT1 and 5-HT2 receptors in most areas of the monkey cerebral cortex suggest that these two receptor subtypes may make differential contributions to cortical functions. PMID- 2918095 TI - Dopamine-like immunoreactivity in the brain and suboesophageal ganglion of the honeybee. AB - The distribution of dopamine in the brain and suboesophageal ganglion of the honeybee Apis mellifera was investigated by means of immunocytochemistry with a well-characterized antiserum against dopamine. The binding of the antiserum in paraffin serial sections was studied with the peroxidase-antiperoxidase method. Dopamine-like immunoreactive neurons are present in most parts of the brain and in the suboesophageal ganglion. Only the optic lobes are devoid of label. There are ca. 330 dopamine immunoreactive somata in each brain hemisphere plus respective suboesophageal hemiganglion, which is less than 0.1% of the entire neuronal population. Most of the labelled somata are situated within three clusters: one below the lateral calyx and two in the anterior-ventral protocerebrum. Other labelled somata lie dispersed or in small groups around the protocerebral bridge, below the optic tubercles, proximal to the ventral rim of the lobula, and in the lateral and ventral somatal rind of the suboesophageal ganglion. Similar to neurons that react with an antiserum against serotonin, the fine processes of dopamine immunoreactive fibers have a varicose appearance which is typical for aminergic neurons. In addition to the neuronal staining, dopamine like immunoreactivity is also present in the sheath surrounding the brain and in the retina, where it is not restricted to any particular cell type. A detailed account is given for those neurons and groups of neurons that could be traced and reconstructed in some detail. A common feature of all dopamine immunoreactive fibers is that each fiber invades large volumes of neuropil, suggesting that dopamine is more important in mediating distant rather than local neural interactions. PMID- 2918096 TI - Neurons of origin and fiber trajectory of amygdalofugal projections to the medial preoptic area in Syrian hamsters. AB - The amygdaloid neurons of origin and the trajectory of amygdaloid fibers to the medial preoptic area of the adult male Syrian hamster were identified by using horseradish peroxidase (HRP) histochemistry. After iontophoresis of HRP into the medial preoptic area, retrogradely labeled amygdaloid neurons were located in the dorsal and caudal parts of the medial amygdaloid nucleus and throughout the amygdalohippocampal area. No amygdaloid neurons were labeled after HRP applications confined to the most rostral portion of the medial preoptic area (anterior to the body of the anterior commissure). Following more caudal medial preoptic area injections (body of the anterior commissure to the suprachiasmatic nucleus) the distribution of retrogradely labeled cells in the medial amygdaloid nucleus and the amygdalohippocampal area revealed no topographic organization of the amygdalopreoptic connections. When amygdaloid neurons were labeled, the amygdalohippocampal area contained two to five times as many HRP-filled cells as the medial amygdaloid nucleus. Retrogradely transported HRP could be followed from the medial preoptic area to the amygdala through fibers in the dorsomedial quadrant of the stria terminalis. In addition, electrolytic lesions of the stria terminalis prior to iontophoresis of HRP into the medial preoptic area prevented retrograde transport to neurons in both the dorsocaudal medial amygdaloid nucleus and the amygdalohippocampal area. These results confirm earlier observations describing the location of autoradiographically labeled efferents from the medial amygdaloid nucleus to the medial preoptic area and provide new information about the restricted region within the medial amygdaloid nucleus from which these projections arise. They also suggest that, unlike the projections from the medial amygdaloid nucleus to the bed nucleus of the stria terminalis, the efferents to the medial preoptic area travel entirely in the stria terminalis. PMID- 2918097 TI - Morphologies of rabbit retinal ganglion cells with concentric receptive fields. AB - Rabbit retinal ganglion cells with concentric receptive fields were intracellularly recorded and stained in the isolated superfused eyecup preparation to relate specific physiological response properties to dendritic morphology. Concentric ganglion cells, as traditionally defined, were those that had On or Off centers with antagonistic surrounds but lacked complex response properties such as direction or orientation selectivity. Concentric cells were classified into different groups by extracellular recordings of their On- or Off center response sign, excitatory receptive field center size, linearity of spatial summation, and brisk vs. sluggish and transient vs. sustained responses to step changes in light intensity. The cells were then impaled, confirmed in identity during intracellular recording, and iontophoretically injected with horseradish peroxidase for histological analysis. Twenty-three concentric ganglion cells were recovered and morphometrically analyzed. Their physiological response properties were found to be related to a number of underlying two- and three-dimensional attributes of the cell's dendritic branching patterns. The dendrites of all 20 brisk concentric cells and two of the three sluggish cells were found to ramify narrowly in either the proximal or distal half of the inner plexiform layer, corresponding to whether they are On center or Off center, respectively. One of the sluggish concentric cells was found to have a more complex, partially bistratified ramification. Physiologically identified brisk sustained-linear, brisk-transient-nonlinear, brisk-transient-linear, and at least two classes of sluggish concentric ganglion cells were stained. Each of these physiological classes appears to exhibit a distinct and identifiable dendritic branching pattern. PMID- 2918098 TI - Morphologies of rabbit retinal ganglion cells with complex receptive fields. AB - Ganglion cells that had complex receptive field properties, namely, On-Off and On direction-selective cells, orientation-selective cells, local edge detectors, and uniformity detectors (suppressed by contrast cells) were recorded in an isolated superfused rabbit eyecup preparation. Cells were first classified by their characteristic extracellular responses to manually controlled stimuli similar to those which have been used in previous in vivo studies. Ganglion cells were then impaled, confirmed in identity by intracellular recording, and iontophoretically injected with horseradish peroxidase for staining. Twenty-two ganglion cells, which included members of all the major classes mentioned above, were recovered from the visual streak or near periphery. All recovered cells were drawn in camera lucida from flat-mounted retinas and entered into a computer as two dimensional stick figures; nearly all were three-dimensionally reconstructed to determine the level and manner of dendritic ramification in the inner plexiform layer (IPL). The location of ganglion cell dendrites in sublaminar regions of the IPL was found to be consistent with the hypothesis of a division of the IPL into excitatory On (proximal) and Off (distal) sublaminae, with some qualifications for particular classes. Each of the complex receptive field ganglion cell classes exhibited a distinctive three-dimensional dendritic arborization pattern uniquely associated with that physiological class. PMID- 2918099 TI - Ganglion cell arrangement and axonal trajectories in the anterior lateral line nerve of the weakly electric fish Apteronotus leptorhynchus (Gymnotiformes). AB - To determine the organizational principles underlying the peripheral electrosensory nervous system of weakly electric gymnotiform teleosts we labelled each of the four anterior lateral line nerve branches with HRP. We determined the position of labelled cell bodies within the ganglion and followed anterogradely filled fibers to their termination sites in one of the four somatotopic maps in the electroreceptive lateral line lobe (ELL). Within the ganglion, cell bodies exhibit a loose somatotopy based on nerve branch position: trunk electroreceptors have their cell bodies located in the caudal ganglion; cell bodies to the head receptors are rostral. Cell bodies to the head exhibit a rough dorsoventral polarity, supraorbital cells tend to be located dorsally, infraorbital cells centrally, and mandibular cells ventrally. Despite this general somatotopy there is substantial overlap (up to 30%) of cell bodies among regions. There appears to be no rostrocaudal topography within nerve branch regions. Iontophoretic WGA-HRP injected into the medial segment of the ELL retrogradely labelled cell bodies that innervate ampullary organs. These cell bodies were dispersed throughout the ganglion, indicating that cell bodies do not cluster by receptor type. Peripherally directed axons from the ganglion appear to undergo an active reorganization in order to form the nerve branches. Within nerve branches, axons to a particular area of skin do not cluster together. Centrally from the ganglion, axons retain the position of their cell body until they reach the ELL border. Once in the ELL, fibers become sorted in the deep fiber layer according to receptor type and the map they terminate in. This reorganization involves rearrangement of fascicles and axons within fascicles. In toto, proceeding from peripheral to central, the electrosensory periphery loses at least a portion of its receptor topography in the distal nerve and ganglion and then acquires both a functional and somatotopic organization after reaching the ELL; conceptually it is torn down and rebuilt again. From an ontogenetic perspective, axonal growth occurs from the ganglion outward; the fact that ganglion cell bodies are not highly organized while the receptors they innervate and their central processes are suggests that active axonal guidance mechanisms are involved. PMID- 2918100 TI - Distribution of neuropeptide Y-containing perikarya and axons in various neocortical areas in the macaque monkey. AB - The laminar and areal distribution of neuropeptide Y (NPY)-containing perikarya and their processes was analyzed immunocytochemically in Brodmann's neocortical areas 17, 18, 7, 22, 3, 4, 24, and 9 (Walker's area 46) in seven macaque monkeys. Most NPY-containing cells are distributed in two broad bands in layers II-III and V-VI in all areas; relatively few cells can be found in layer I and virtually none in layer IV. Numerous NPY-containing cells are situated in the white matter immediately subjacent to the cortical gray. Severalfold regional and individual differences in the density of NPY-positive somata were found in supra- and infragranular layers. However, the interareal variations in the density of NPY containing somata do not conform to a universal pattern, because of either individual variability or inherent difficulties in standardizing immunocytochemical labeling. In contrast, the laminar differences in the distribution of NPY-containing axons among cortical areas are consistent in all animals. In general, primary sensory and motor areas have a lesser density of NPY containing axons than association and limbic areas. Within the general pattern, area-specific laminar segregation of NPY-containing axons occurs. The regional differences in the distribution of NPY-like immunoreactivity in the neocortex may reflect innate characteristics of local neuronal circuits serving specialized functions. PMID- 2918101 TI - Multiple types of neuropeptide Y-containing neurons in primate neocortex. AB - The avidin-biotin-peroxidase method was used at the light and electron microscopic levels to analyze neuropeptide Y (NPY)-containing neurons in the neocortex of six adult macaque monkeys. Regions studied included various sensory, motor, limbic, and association areas, designated as 17, 18, 7, 22, 3, 4, 6, 24, and 9 by Brodmann (Beitrage zur Histologischen Lokalisation der Grosshirnrinde. Leipzig: Barth, '06). Several types of NPY-containing neurons can be distinguished by their laminar location, by the size of their perikarya, and by the size, shape, and pattern of ramification of their processes: 1) layer I small local circuit neurons; 2) layer II granule cells; 3) aspiny stellate cells located in layers II-III and V-VI, with long, slender dendrites; 4) sparsely spiny stellate cells; 5) aspiny stellate cells with long, horizontally oriented dendrites, whose cell body is situated in layer VI; 6) Martinotti cells in areas 9, 7, and 24; and 7) multipolar neurons situated in the white matter subjacent to the cortical gray. The possibility of additional neuronal types containing NPY is suggested by labeled densely spinous dendrites in area 6 and recurving axons and axonal loops in the supragranular layers in areas 7 and 9. No NPY-containing neurons were found in layer IV of any area, except layers IVA and B of the visual cortex. Likewise, nonneuronal elements were not labeled. The regional differences in the distribution of some NPY-containing neuron types may reflect adaptations of local neuronal circuits for specialized functions. PMID- 2918102 TI - Fluorescent histochemical localization of neutral endopeptidase-24.11 (enkephalinase) in the rat spinal cord. AB - The localization of neutral endopeptidase-24.11 (E.C. 3.4.24.11; enkephalinase) in rat spinal cord was investigated by a novel fluorescent histochemical method. Enkephalinase was localized by using a coupled enzyme assay based upon the sequential cleavage of the synthetic peptide substrate glutaryl-ala-ala-phe-4 methoxy-2-naphthylamide by enkephalinase and exogenous aminopeptidase M. Enzyme distribution was examined in segments from cervical, thoracic, lumbar, and sacral cord. At all spinal cord levels, enkephalinase was localized to discrete regions of the gray matter. The substantia gelatinosa displayed rich enkephalinase staining which overlapped the inner and outer zones of lamina II. A staining pattern similar to that observed in lamina II was observed in the spinal trigeminal nucleus in the medulla. In lamina III the enzyme was associated with small and medium-sized cells. Lamina IV showed staining associated with medium sized and large cell bodies. The medial boundary of the dorsal gray of laminae IV and V had medium-sized fusiform cells which stained for enkephalinase. In the lateral reticulated areas of lamina V, enkephalinase reaction product was localized to scattered medium-sized and large cells compressed against the white matter of axon bundles. Staining in lamina VI was similar in appearance to lamina V. Enkephalinase reaction product was widely distributed in the ventral horn. Numerous ventral horn motor neurons of varied size and morphology in laminae VIII and XI stained richly for the enzyme. The enzyme was also localized to medium sized and large cells in lamina X and to cells of the central cervical nucleus. The size and morphology of the cell types associated with the enzyme supported a neuronal association for enkephalinase. The regional distribution of the enzyme overlapped that of enkephalin- and substance-P rich regions of the spinal cord. These findings support a role for enkephalinase in the metabolic regulation of centrally acting neuropeptides. PMID- 2918103 TI - Shape and distribution of an unusual retinal neuron. AB - Rabbit retinas were exposed to exogenous indoleamines and fixed with mixed aldehydes. The indoleamines were accumulated by two types of amacrine cell and by an unusual cell (type 3) that branches widely in both plexiform layers. The type 3 cells were studied after immunohistochemistry, photooxidation of the fluorescent label, or injection with Lucifer Yellow. Their cell bodies are located at the scleral margin of the inner nuclear layer. The cells' arbors in the outer plexiform layer range from 800 to 1,500 microns in diameter. A descending process crosses the inner nuclear layer and branches in layer 5 of the inner plexiform layer. The arbor in the inner retina can exceed 500 microns in diameter. The distribution of type 3 cells was mapped in a series of retinal whole mounts. The number of type 3 cells ranged from 58 to 270 in different retinas. In two retinas from a single animal, however, it was virtually identical. Type 3 cells are concentrated in the region ventral to the visual streak, so that large areas of the retina are not covered by any type 3 cell. Because of their incomplete retinal coverage and variable number from animal to animal, the type 3 cells appear to be developmental anomalies. Paradoxically, their generation must be precisely controlled because of the numerical symmetry between an individual animal's two eyes. PMID- 2918104 TI - Variations in the intralobular distribution of copper in the livers of copper loaded rats in relation to the pathogenesis of copper storage diseases. AB - There are differences in the hepatic intralobular distribution of copper in copper storage related diseases which may be of pathogenetic significance. Male rats fed a high copper diet (1500 ppm) for 16 weeks were killed at intervals in an attempt to compare copper distribution in their livers with those in human, canine and ovine copper toxicosis. Copper was found to accumulate almost exclusively in the periportal and mid-zones of the rat liver lobules and was associated with progressive pathological changes which included focal and periportal degeneration and necrosis. This pattern of copper distribution contrasts markedly with the centrilobular retention reported in familial canine copper toxicosis and chronic copper poisoning in sheep which suggests that, in these conditions, a secretory deficiency may be less important than a metabolic zonal defect of intracellular copper metabolism. The pathological changes observed in copper-loaded rats have a different micro-anatomical localization from those in dogs and sheep, but show similarities to the early changes reported in the latter species and indicate the possibility of a similar cellular lesion. PMID- 2918105 TI - Multinucleate giant cells in the regressed corpus luteum of the bitch. AB - The pigmented cell clusters which make up the residual luteal tissue in the canine ovary were found to be mostly syncytial in nature and to resemble the foreign-body and Langhan's-type giant cells of chronic inflammation. PMID- 2918106 TI - Cartilaginous metaplasia associated with a basal cell tumour in a dog. AB - Locally extensive dermal cartilaginous metaplasia was seen in association with a pigmented basal cell tumour in an aged, spayed Basenji dog. Six months after surgical excision, the animal remains healthy with no recurrence of the neoplasm. PMID- 2918107 TI - Post-mortem changes in the abomasal mucosae of sheep infected with Haemonchus contortus compared with those in uninfected sheep. AB - Progressive post-mortem changes were observed, with fibre optic endoscopy, in the abomasum of uninfected sheep and sheep infected with H. contortus. Loss of epithelial cells was observed 14 to 16 min after death in the uninfected sheep. The loss exposed the underlying lamina propria. This loss became more widespread as the time after death increased. Epithelial cell loss was observed earlier (as early as 6 min after death) in the infected sheep. Three of the infected sheep also displayed dispersal of alkaline phosphatase activity 30 min after death. The present work shows that post-mortem changes can occur quite quickly in animals, especially infected animals, and emphasizes the importance of rapid removal of tissue from animals after death. PMID- 2918108 TI - Occurrence of the lungworms Capillaria and Crenosoma spp. in British hedgehogs (Erinaceus europaeus). AB - Fifty-three dead hedgehogs (Erinaceus europaeus) were investigated histologically for evidence of lungworm infestation. The faeces of forty-two were examined microscopically for nematode eggs. Thirty-five animals showed parasitic lesions- fourteen Crenosoma only, five Capillaria only and sixteen both. Infestations were characterized by inflammatory changes in the trachea and lung and the presence of worms in other organs. There was some correlation between the finding of parasites in histological sections and the detection of eggs in faeces but, neither method appears completely reliable. PMID- 2918109 TI - Toxic effects of theobromine on mature and immature male rabbits. AB - Mature and immature male rabbits were fed for 120 and 20 days, respectively, a commercial diet containing theobromine in amounts of 0, 0.5, 1 and 1.5 per cent. Clinical, haematological, histopathological and histoenzymological examinations were performed. Mortality, which appeared dose- and time-related, was severe and rapid, mostly in the 1 and 1.5 per cent groups and was attributed to cardiac failure. Theobromine administration resulted in marked changes in thymus and testes and the severity of lesions appeared to be related to the amounts of the ingested methylxanthine. The earliest thymic alterations in immature rabbits consisted of a blurring of demarcation between cortex and medulla accompanied, in the more advanced stages, by a decreased lymphocyte density. Similar lesions were observed in mature animals which had died in the earlier phase of the study. Testicular alterations ranged from vacuolation of spermatids and spermatocytes to multinucleated cell formation and oligospermia or aspermia with extensive degeneration of tubule cells. Some necrotic and post-necrotic myocardial foci were also recorded. The increase in testicular activity of beta-glucuronidase in immature rabbits compared to the untreated animals provided further evidence of an early theobromine-induced damage of the testes. PMID- 2918110 TI - Experimental induction of pneumonia in mice with Bordetella parapertussis isolated from sheep. AB - The intranasal inoculation of mice with a suspension of ovine isolates of Bordetella parapertussis killed about 11 per cent of animals (four out of 34) between 2 to 3 days post-inoculation and produced a subacute bronchopneumonia morphologically similar to early lesions of naturally occurring ovine chronic non progressive pneumonia. Pulmonary lesions characterized by alveolar septal congestion and oedema, focal alveolar haemorrhage and intraalveolar and septal infiltration by neutrophils and macrophages were seen in the early stages. Bronchioles often contained an exudate of macrophages, neutrophils and fibrin and later hyperplasia of perivascular and peribronchiolar lymphoid tissue and fibrosis of the interalveolar septa were evident. Electron microscopy revealed extensive degenerative changes in the alveolar epithelium and alveolar macrophages. Pure cultures of B. parapertussis were consistently recovered from infected lungs from 12 h after inoculation to pid 6. Intact organisms and organisms showing varying degrees of degeneration were found free in alveolar spaces or phagocytosed by alveolar macrophages. PMID- 2918111 TI - Lymphangiosarcoma and haemangiosarcoma in a cat. AB - Ultrastructural findings in a feline ventral abdominal vascular tumour showed lack of basal lamina, few micropinocytotic vesicles and intercellular junctions and a discontinuous endothelial cell layer. A splenic cyst had a continuous basal lamina, numerous micropinocytotic vesicles and intercellular junctions and a continuous endothelial cell layer. These findings were compatible with diagnosis of lymphangiosarcoma (ventral abdomen and metastases) and haemangiosarcoma (splenic cyst). PMID- 2918112 TI - Metastatic malignant mesothelioma in a dog. AB - A case of malignant mesothelioma in a 5 1/2-year-old St Bernard dog is described. The distribution of the neoplasm was to the pericardium and peritoneum and not the pleura. Distant metastases were found in the bronchial lymph node and bone marrow. PMID- 2918113 TI - The dysplastic melanocytic nevus: a prevalent lesion that correlates poorly with clinical phenotype. AB - We estimated the prevalence of persons with histologic dysplasia in at least one of two nevi examined by biopsy to be 53% in Utah's caucasians. This apparently high prevalence indicates that such lesions may represent a normal variant of a melanocytic nevus, perhaps those in the process of active proliferation. Regardless of the apparent ubiquity of these lesions, examination of biopsy specimens led to a grading scheme of histologic dysplasia that may reflect chronologic stages in the neoplastic development of melanocytic nevi. Comparison of these histologic findings with the clinical examination yielded the unexpected result that dysplasia and lesion size are independent of each other. Lesions 3 mm in diameter or smaller were as likely to be dysplastic as those much larger. There was, however, a statistically significant relationship between histologic dysplasia of a nevus examined by biopsy and the person's total number of melanocytic lesions. This finding indicates that the pathology grading scheme may be useful. The high prevalence of dysplastic nevi dilutes the clinical significance of a dysplastic nevus as an isolated finding and thereby lessens the importance of pathologic findings in the diagnosis of dysplastic nervus syndrome. PMID- 2918114 TI - Personality factors as predictors of therapeutic response to cryosurgery in patients with warts. AB - Fifty patients with warts were treated with cryotherapy and given a 100-item questionnaire, The Tennessee Self-Concept Scale, to complete. Responses from 42 patients on whom follow-up data were available were subjected to computer analysis. The answers to eight of the questions differed significantly between treatment cures (23) and treatment failures (19). Further analysis of two of the eight questions showed that it may be possible to use them to predict cryosurgical treatment success or failure in up to 100% of cases. PMID- 2918115 TI - Easier patch testing with TRUE Test. AB - TRUE Test, a standardized, ready-to-apply patch test system, is made from polyester covered with a film of allergens incorporated in a hydrophilic polymer. The patches are mounted on nonwoven cellulose tape with acrylic adhesive, covered with siliconized plastic, and packed in an air-tight and light-impermeable envelope. When the test strip is taped on the skin, perspiration hydrates the film and transforms it to a gel, which causes the allergen to be released. The first panel of 12 allergens and allergen mixes is standardized and tested for stability in vitro and in vivo. The accuracy of the test panel has been certified in international multicenter studies by comparing it with present patch test techniques. A second panel of 11 more allergens was completed in 1988. The two test panels include the full standard panel of the North American Contact Dermatitis Group. PMID- 2918116 TI - Epidermal nevi and the epidermal nevus syndrome. A review of 131 cases. AB - One hundred thirty-one patients with epidermal nevi are reviewed. The commonest site of involvement was the head and neck, and 13% of patients had widespread lesions. Ages of onset ranged from birth to 14 years. A spread beyond the original distribution was noted in 37% of patients. Many clinical patterns occurred, including eight cases of inflammatory linear verrucous epidermal nevus. A variety of other cutaneous abnormalities were found. Biopsies were performed in 41 cases. Three patients developed secondary tumors. One hundred nineteen of the patients were assessed for the presence of abnormalities in other organ systems. One or more abnormalities were demonstrated in 33% of patients, and in 5%, five or more abnormalities were detected. This study indicates that patients with epidermal nevi are at significant risk of having other abnormalities and warrant detailed initial assessment and close follow-up. PMID- 2918117 TI - Histologic studies in psoriatic patients treated at the Dead Sea: comparison with photochemotherapy. PMID- 2918118 TI - Postirradiation Merkel cell carcinoma. PMID- 2918119 TI - Contact dermatitis to transdermal estradiol system. PMID- 2918120 TI - Ciguatera fish poisoning. PMID- 2918122 TI - Against time-limited certification. PMID- 2918121 TI - Successful treatment of the pruritus of human immunodeficiency virus infection and acquired immunodeficiency syndrome with psoralens plus ultraviolet A therapy. PMID- 2918123 TI - Use of the ophthalmoscope in the clinical diagnosis of cutaneous pigmented lesions. PMID- 2918124 TI - Examination of the male genitalia with an ophthalmoscope: a rapid and simple approach to the detection of penile venereal warts. PMID- 2918125 TI - Psoriasis: neutrophil chemotaxis and microbial factors. PMID- 2918126 TI - Melanocytic nevus counts and melanoma. PMID- 2918127 TI - Corticosteroids and postherpetic neuralgia. PMID- 2918128 TI - Primary amyloidosis of the concha. PMID- 2918129 TI - Bed sores and amyotrophic lateral sclerosis. PMID- 2918130 TI - Biophysical analyses of sequential bands of enamel related to ruffle-ended and smooth-ended maturation ameloblasts. AB - During amelogenesis in the rat incisor, modulating ruffle-ended (RA) and smooth ended (SA) ameloblasts are distributed as bands in the enamel organ of the maturation zone. This distribution of the two cell types has been shown to be precisely correlated with a banding of the underlying enamel, as shown by staining and other cyclical indicators (Takano et al., 1982a,b). Several biophysical approaches have been taken here to characterize the enamel bands sequentially and to determine whether the appearance of such bands is attributable to differences in inorganic composition possibly related to RA and SA. Sprague-Dawley rats were decapitated under ether anesthesia, lower incisors were dissected from surrounding alveolar bone, and enamel organs were wiped from the teeth with moistened gauze. Analyses were performed on either the surface of intact enamel or on individual strips of enamel dissected from the tooth surface, by use of the translucent bands that appear during drying as reference marks for the positions of the overlying cell type. X-ray diffraction (XRD), infrared spectroscopy (IR), x-ray photoelectron spectroscopy (XPS), and wave-length dispersive electron probe x-ray micro-analysis (WDS) all failed to detect significant differences between analysis areas; data were characteristic of enamel apatite having typical XRD maxima (hkl = 002, 211, 112, 300), IR absorption bands (PO4(3-) and CO3(2-], XPS Ca and P binding energies (Ca2p = 350.5, 346.9 eV; P2p = 133.7, 132.7 eV), and WDS Ca/P molar ratios (1.33 1.49).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918131 TI - Microstructural features of carious human enamel imaged with back-scattered electrons. AB - We have used back-scattered electrons (BE) in the scanning electron microscope to produce mineral density images of enamel. Flat surfaces of artificially-carious enamel, softened in an intra-oral experiment, and naturally-carious (white spot) enamel were polished to a high gloss with diamond lapping compound, rendering them almost featureless by secondary electron scanning electron microscopy. They were then examined at 10 to 30 kV in a Philips 505 instrument fitted with a 4 quadrant BE detector. Study of surfaces prepared approximately parallel to the natural surface showed that mineral was lost from both prism core and the interprismatic region, leaving a thin mineral-rich rim at the prism periphery. The same lesions viewed longitudinally on a surface prepared perpendicular to the natural surface showed mineral-rich bands at the prism margins in the outer enamel. Near the advancing front of the lesion, the prism junctions were widened and the prism cores sometimes hypermineralized. Natural lesions sectioned in the prism long axis showed features previously seen with other techniques, e.g., cross-striations and striae of Retzius, but in much greater detail. Mineral enrichment at the prism periphery in the lesion body and a widening of the prism junction at the advancing fronts of lesions in permanent teeth were most obvious. Calculations showed that with an accelerating voltage of 30 kV, the images reflected mineral density up to 4 microns beneath the surface. BE microscopy produces a high-resolution image of mineral loss or gain in carious enamel, with relatively easy sample preparation. PMID- 2918132 TI - Effects of sustained-release chlorhexidine acetate on the human dental plaque flora. AB - The aim of this study was to determine the effect on the human dental plaque flora of a varnish containing chlorhexidine diacetate. The in vitro release of chlorhexidine acetate from the varnish preparation was relatively fast on the first day, followed by a substantial decline in the subsequent three days. In a clinical experiment, 26 volunteers were randomly distributed over four experimental groups. After a dental prophylaxis, the subjects were treated with a single application of a placebo varnish (group I), a fluoride varnish (group II), a chlorhexidine varnish (group III), or a fluoride-plus-chlorhexidine varnish (group IV). Saliva and pooled plaque samples from approximal surfaces were taken before (baseline) and one, two, three, four, and six weeks after the treatments. No suppression was found of total cultivable flora or S. sanguis after the experimental treatments. Application of the fluoride varnish did not suppress the A. viscosus/naeslundii or S. mutans levels in the dental plaque. Chlorhexidine suppressed A. viscosus/naeslundii until two weeks after the treatment. S. mutans was significantly suppressed until four weeks after a single chlorhexidine application. While in some subjects S. mutans was effectively suppressed over the whole experimental period, in others S. mutans recovered quickly. In five subjects in whom S. mutans recovered quickly, the dentition was treated twice with chlorhexidine varnish, with an interval of one week between the treatments. After two chlorhexidine treatments, S. mutans in saliva and on the teeth was suppressed more strongly than after a single treatment. However, the second chlorhexidine treatment could not prevent the return of S. mutans in the approximal areas to its original level. PMID- 2918133 TI - Protein dissimilation by human salivary-sediment bacteria. AB - Proteins of known composition and structural characteristics were incubated (1.0 mg/mL) with re-suspended salivary sediment (2.5% v/v) in a lactate-salt medium with an initial pH of 5.2 for two hr at 37 degrees C. Hydrolysis of the proteins was monitored by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Hydrogen ion, amines, and ammonia were measured by use of a combined pH electrode, high-performance liquid chromatography, and glutamate dehydrogenase, respectively. Of the proteins studied, the caseins alpha s1, beta, and kappa and the histones H1 and H3 were extensively hydrolyzed by the salivary-sediment bacteria. The hydrolysis of these proteins was attributed to their relative lack of tertiary (folded) structure. The only amine detected was the polyamine putrescine arising from the catabolism of arginine following the hydrolysis of the arginine-rich histone H3. None of the other proteins extensively hydrolyzed by salivary sediment, although containing arginyl and lysyl residues, served as substrates for putrescine or cadaverine production. Pre-hydrolysis of the arginine-rich histone H3 and poly-L-arginine with trypsin resulted in a marked increase in putrescine produced, suggesting that the salivary-sediment proteolytic activity was not "trypsin-like". Incubation of salivary-sediment bacteria with the caseins and the histone H3 resulted in an increase in ammonium ion concentration and an associated decrease in hydrogen ion concentration. The increase in ammonium ion concentration not attributed to arginine hydrolysis was correlated with the content of glutaminyl plus asparaginyl residues of the proteins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918134 TI - Fluoride in plaque following use of dentifrices containing sodium monofluorophosphate. AB - Previous work showed that plaque fluoride increased with increasing NaF content of mouthwashes following daily use. The main aim of this study was to test whether a similar relationship was detectable after regular use of dentifrices containing amounts of sodium monofluorophosphate equivalent to 1000, 1500, and 2500 micrograms F/g. Plaque was collected from three groups, each consisting of approximately 80 children, who had each used one of the dentrifrices for one year. Plaque fluoride increased significantly with increasing Na2FPO3 content of the dentifrices. For the 1000-micrograms-F/g group, plaque fluoride also increased significantly with increasing frequency of dentifrice use, but did not correlate with amount of dentifrice applied per brushing. The inverse correlation observed between mean plaque fluoride concentrations and mean three-year caries increments suggests that oral fluoride measurements may prove valuable in estimating the likely anti-caries efficacy of fluoride-containing dental products. PMID- 2918135 TI - Tempering stresses in feldspathic porcelain. AB - The objective of this study was to develop an analytical model to calculate transient and residual (tempering) stresses in dental porcelain plates subjected to cooling rates used by commercial laboratories. The model incorporates linear viscoelasticity and structural relaxation effects. The viscosities of three experimental body porcelains and three experimental opaque porcelains as a function of temperature were calculated from creep rates measured in a bending beam viscometer. Measurements were made under thermal equilibrium conditions for temperatures ranging from 550 degrees C to 625 degrees C. Thermal expansion data measured in a differential dilatometer at slow heating rates were supplied by the manufacturer. Temperature distribution in the plates as a function of convective heat transfer coefficient, initial plate temperature, and plate thickness was calculated by use of standard numerical techniques. Calculations of transient and residual stress were performed for one body porcelain, for two plate thicknesses, and for three variable cooling rates. Calculated surface residual stresses were strongly dependent on plate thickness, cooling rate, and initial soak temperature. For the cases studied, the maximum residual surface compressive stress was 26.4 MPa. PMID- 2918136 TI - Studies on fluoride concentrations in human submandibular/sublingual saliva and their relation to flow rate and plasma fluoride levels. AB - Submandibular/sublingual saliva and blood were collected from five subjects after ingestion of 1 mg fluoride as NaF. An individual collection device, made from a silicone impression material, was used to collect the saliva in 10-minute samples, before and during 2 hr after the fluoride intake. In two separate experiments on each individual, submandibular/sublingual saliva was collected continuously at different flow rates: without stimulation and with gustatory stimulation. Blood was also collected at intervals throughout the experiments. The concentration of fluoride in the submandibular/sublingual saliva was less than that in the plasma but independent of salivary flow rate. The ratio between the saliva and plasma fluoride concentrations at the peak of the mean plasma fluoride concentrations was 0.55 +/- 0.13 and 0.69 +/- 0.11 in the experiments on unstimulated and stimulated salivary, flow rate, respectively. The total amount of the ingested fluoride dose that was excreted through the submandibular/sublingual glands during 130 min was highly correlated with the salivary flow rate. The fraction of the ingested fluoride dose excreted in 2 hr was 0.04 +/- 0.02% in the unstimulated saliva and 0.15 +/- 0.09% in the stimulated saliva. PMID- 2918137 TI - The detection of incipient caries with tracer dyes. AB - The purpose of this study was to determine the increase in color contrast produced by the use of a tracer dye in detection of incipient caries lesions with transillumination. Twenty-four caries-free first premolars were immersed in an acid gelatin for production of artificial incipient caries lesions. After the lesions had developed, these teeth were photographed by transillumination. Two photographs were taken of each tooth. The first photograph showed the lesion without dye. A blue tracer dye was then added and absorbed by the lesion, and a second photograph was taken. The data on the color difference were obtained by use of a reflectance colorimeter and showed a four-fold increase between the lesion and surrounding area with the dye. A two-way analysis of variance was used for the statistical interpretation. The color difference between the lesion without the dye and then with the dye was significant. The use of the blue tracer dye, therefore, significantly increased the contrast in the images of the artificial incipient lesions. PMID- 2918138 TI - What's in a name? The function of the mineralized tissue matrix proteins. PMID- 2918139 TI - Correlation of dental amalgam crevice corrosion with clinical ratings. AB - In vitro corrosion behavior of gamma 2-containing and gamma 2-free dental amalgams was examined under crevice conditions which simulated the amalgam-tooth interface. By means of potentiostatic testing, current-density/time behavior and integrated anodic current were measured for 16 hr. All of the amalgams demonstrated crevice corrosion susceptibility. Crevice corrosion propagation for gamma 2-free vs. gamma 2-containing amalgams was characterized by lower acceleration and maximum rates during the most dynamic period. Integrated anodic current results were correlated with marginal breakdown ratings reported in two clinical investigations. Strong and significant coefficients were found between integrated current and marginal breakdown ratings when gamma 2-containing and gamma 2-free amalgams were correlated as a single group, but not when correlated separately. PMID- 2918140 TI - The influence of polyacid molecular weight on some properties of glass-ionomer cements. AB - The influence of the molecular weight of the poly(acrylic acid) component on some properties of glass-ionomer cement has been investigated. The results can be explained by treatment of glass-ionomer cements as thermoplastic composites. Many of the concepts of polymer science can be applied successfully in a qualitative way to these cements, including the ideas of entanglements and reptation. Molecular weight of the polyacid had a pronounced influence on setting rate, acid erosion rate, toughness, fracture toughness, and wear resistance. The chain length of the polyacid was found to be an important parameter in formulation of a cement, and the higher the molecular weight, the better the properties. However, in practice the molecular weight is limited by viscosity, and some balance has to be achieved among concentration, molecular weight, and viscosity. PMID- 2918142 TI - Perspectives incite responses. PMID- 2918141 TI - Professional satisfaction. PMID- 2918143 TI - Continuing "cause for concern". PMID- 2918144 TI - Diagnostic radiographs. PMID- 2918145 TI - Lingual orthodontic treatment. PMID- 2918146 TI - Not a season for discontent. PMID- 2918147 TI - Inside the ADA. PMID- 2918148 TI - Physician and dentist compliance with American Heart Association guidelines for prevention of bacterial endocarditis. AB - To determine the rate of physician and dentist compliance with the American Heart Association's (AHA) recommendations for prophylaxis against bacterial endocarditis--considered the standard of care--questionnaires were mailed to 1,131 dental and medical practitioners. They were asked to identify various cardiac conditions requiring prophylaxis and dental procedures that would cause a bacteremia, and to write prescriptions for prophylactic antibiotics for five different scenarios. Both groups had low compliance with AHA recommendations (32.9% collectively) when prescribing appropriate antibiotic regimens for bacterial endocarditis prophylaxis. PMID- 2918149 TI - 'Usual and customary' practice versus the recommendations of experts: clinician noncompliance in the prevention of bacterial endocarditis. AB - Data were collected from a representative sample of American general practitioners to ascertain adherence to the recommendations by the American Heart Association (AHA) concerning management of patients at risk for bacterial endocarditis. Inconsistencies were found in the prescribing of appropriate risk related therapies such as proper timing, selection of antibiotics, and associated dosages. It is suggested that clinicians' compliance level with these recommendations may be raised by a careful reading of the AHA's latest findings. PMID- 2918150 TI - Oral manifestations of Ehlers-Danlos syndrome: report of case. AB - First described in the beginning of this century, Ehlers-Danlos syndrome is a hereditary connective tissue disorder. This case report describes an 11-year-old girl who had frequent unexplainable bruises. During an initial orthodontic evaluation, characteristic symptoms were spotted, and a subsequent diagnosis made. PMID- 2918151 TI - Marginal ridge strength of restored teeth with modified Class II cavity preparations. AB - This study compared marginal ridge fracture resistance in two groups of teeth restored with modified Class II cavity preparations, with control groups. The results indicated that the composite resin and dental amalgam restored teeth fractured at compressive loads that were not statistically different from those of the control (unprepared, intact) teeth. The marginal ridges of the unrestored, prepared teeth were significantly weaker. PMID- 2918153 TI - Accredited dental schools. Commission on Dental Accreditation. PMID- 2918152 TI - Painless verrucoid plaque on the lower lip. AB - Verruca vulgaris is an uncommon oral lesion which is caused by an infectious agent, HPV. These growths have many clinical features in common with other oral lesions, the most serious of which are verrucous carcinoma and verrucoid squamous cell carcinoma. These various lesions can usually be separated on the basis of clinical and microscopic features. In some cases, however, immunohistochemical studies and DNA hybridization studies may be necessary before an exact diagnosis can be made. PMID- 2918154 TI - Revised ANSI/ADA specifications No. 28 for root canal files and reamers, type K, and No. 58 for root canal files, type H (Hedstrom). Council on Dental Materials, Instruments, and Equipment. PMID- 2918155 TI - Risk factor profiles of patients with sudden cardiac death and death from other cardiac causes: a report from the Coronary Artery Surgery Study (CASS). AB - Identification of patients at risk of sudden death is essential if optimal preventive treatment strategies are to be developed. In the Coronary Artery Surgery Study (CASS) Registry, 19,946 patients were analyzed to characterize baseline clinical, hemodynamic and angiographic features of patients dying from sudden cardiac death and to compare them with features of patients dying from other cardiac causes, of those dying from noncardiac causes and of survivors. Of the 11,843 medically treated patients, 1,621 died during a mean follow-up period of 5.0 years: death was sudden in 557 (34%), nonsudden but cardiac in 813 (50%) and noncardiac in 251 (16%). In 8,103 surgically treated patients, 824 deaths occurred during a mean follow-up period of 5.1 years: death was sudden in 204 (25%), nonsudden but cardiac in 390 (47%) and noncardiac in 230 (28%). In general, the patients (both medically and surgically treated) who died of cardiac causes, either suddenly or nonsuddenly, were similar to each other but significantly different from patients who either survived or died of noncardiac causes. Although patients with an increased risk of any type of cardiac death could be identified, there were no measures of angiographic or hemodynamic characteristics that were significantly different between patients with sudden cardiac death and those with nonsudden cardiac death. Identification of patients at high risk for sudden cardiac death will require approaches in addition to clinical, angiographic and hemodynamic assessment, such as electrophysiologic assessment or monitoring techniques to identify triggering mechanisms. PMID- 2918156 TI - Anomalous coronary arteries: location, degree of atherosclerosis and effect on survival--a report from the Coronary Artery Surgery Study. AB - Limited information is available about clinical presentation, degree of atherosclerosis and effect on overall survival in a large series of patients with coronary artery anomalies. From the National Heart, Lung, and Blood Institute Multicenter Coronary Artery Surgery Study (CASS), detailed coding of coronary angiograms was available in 24,959 patients. Of these patients, 73 (0.3%) had major coronary artery anomalies: 70 had one coronary anomaly and 3 had two coronary anomalies. The most common anomaly involved the circumflex coronary artery (60%). In 69% of these, the circumflex artery arose from a separate ostium in the right coronary sinus, and in 31% it originated as a branch of the right coronary artery. The most common anomalous course was anterior or posterior to the great vessels but not between the great vessels. The major exception to this finding was an anomalous right coronary artery; 7 of 15 such arteries coursed between the great vessels. Anomalous circumflex coronary arteries had a significantly greater degree of stenosis than that in nonanomalous arteries in age- and gender-matched control patients (p = 0.02). Despite this difference, at 7 years there was no significant difference in survival by location or degree of stenosis in the anomalous artery. PMID- 2918157 TI - Intravenous diltiazem for termination of reentrant supraventricular tachycardia: a placebo-controlled, randomized, double-blind, multicenter study. AB - To assess the efficacy and safety of intravenous diltiazem, 54 patients with inducible sustained supraventricular tachycardia received diltiazem, 0.25 mg/kg or 0.25 mg/kg, followed by 0.35 mg/kg body weight, or placebo in a double-blind, randomized study. Twenty patients had atrioventricular (AV) node reentrant tachycardia, whereas 34 had orthodromic AV reciprocating tachycardia associated with the Wolff-Parkinson-White syndrome. Supraventricular tachycardia was terminated in 24 (86%) of 28 patients given intravenous diltiazem compared with 5 (19%) of 26 given placebo (p = 0.0000014). Nineteen (95%) of 20 patients initially given placebo had termination of supraventricular tachycardia after receiving diltiazem. Overall, 43 (90%) of 48 patients receiving intravenous diltiazem had conversion of supraventricular tachycardia to sinus rhythm; the median time to tachycardia termination was 2 min after initiation of a 2 min diltiazem infusion. All 20 patients (100%) with AV node reentrant tachycardia treated with diltiazem had conversion of tachycardia to sinus rhythm as did 26 (81%) of 30 patients with AV reciprocating tachycardia treated with diltiazem. Diltiazem prolonged refractoriness and slowed conduction of the AV node and thereby provided antiarrhythmic action to cause tachycardia termination. Diltiazem had no effect on the electrophysiologic properties of accessory AV connections. Adverse effects were seen in 3 (6%) of the 48 patients given diltiazem. For paroxysmal supraventricular tachycardia initiated in the electrophysiology laboratory, it is concluded that intravenous diltiazem is safe and very effective for acute tachycardia termination when the AV node is part of the reentrant circuit. PMID- 2918158 TI - Hemodynamic progression of aortic stenosis in adults assessed by Doppler echocardiography. AB - Doppler echocardiography was used to follow the hemodynamic severity of aortic stenosis. First, the reproducibility of repeat recordings (mean interval 28 +/- 36 days) of aortic jet velocity, made by two independent observers, was tested in 38 adults with aortic stenosis and unchanged clinical status. The two recordings of maximal velocity correlated well (r = 0.96, y = 0.88x + 0.46m/s, SEE = 0.21 m/s) with a mean coefficient of variation of 3.2%. Repeat recording of left ventricular outflow tract velocity by two independent observers in 10 other patients with aortic stenosis also correlated well (r = 0.94, y = 1.06x + 0.0 m/s, SEE = 0.06 m/s) with a mean coefficient of variation of 4.6%. Next, Doppler echocardiography was used to study 42 patients with aortic stenosis (mean age 66 years) over a follow-up interval of 6 to 43 months (mean 20). Maximal aortic jet velocity increased by 0.36 m/s per year (range -0.3 to +1.0 m/s per year). Mean transaortic pressure gradient changed by -7 to +23 (mean 8) mm Hg/year. Aortic valve area by the continuity equation (n = 25) decreased by 0 to 0.5 cm2/year (mean decrease 0.1 cm2/year). Some patients had a worsening of stenosis (decrease in valve area) even though they had no change or a decrease in pressure gradient, because of concurrent decreases in transaortic volume flow. Twenty-one patients (50%) developed new or progressive symptoms of aortic stenosis necessitating valve replacement.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918159 TI - Aortic stenosis: most cases no longer require invasive hemodynamic study. PMID- 2918160 TI - Prospective two-dimensional echocardiographic evaluation of left ventricular thrombus and embolism after acute myocardial infarction. AB - To determine whether two-dimensional echocardiography can identify patients with left ventricular thrombus after myocardial infarction who are prone to embolism, clinical and echocardiographic variables in 541 patients with a first infarction between 1979 and 1983 were studied prospectively. The first echocardiogram showed definite thrombus in 115 patients (Group 1, 21%) and no thrombus in 426 (Group 2, control). In Group 1, 27 patients (23%) had clinical evidence of systemic embolism related to the thrombus before referral (Group 1a) and 88 did not (Group 1b); these two groups were similar in age, gender and infarct location, but more Group 1a patients were within 1 month of the acute infarction. In both Groups 1a and 1b, the thrombus was found in apical views over asynergic zones, with no difference (p greater than 0.05) between the two groups in the size (average area from two views being 5.3 versus 4.5 cm2), type (protruding in apical views 30% versus 27%), location (apical 83% versus 86%; septal 11% versus 11%; posterior 4% versus 2%), extent of asynergy (31% versus 33%) and ejection fraction (33% versus 34%). However, the frequency of anticoagulant therapy was less (26% versus 63%, p less than 0.005), adjacent hyperkinesia greater (100% versus 49%, p less than 0.005) and thrombus mobility greater (81% versus 19%, p less than 0.005) in Group 1a than in Group 1b. Serial echocardiograms revealed a decreased size of the thrombus by 6 months in both Groups 1a and 1b, and little or no trace in 85% by 24 months. Thus, ventricular thrombus size, location and protrusion in apical views on echocardiography did not correlate with embolism. In contrast, thrombus mobility, the presence of adjacent hyperkinesia and thrombus protrusion assessed in multiple views appeared to be strong discriminators of thrombus prone to embolism. These echocardiographic features might provide a guide for the duration of anticoagulant therapy. PMID- 2918161 TI - Characterization of the acute left ventricular thrombus: hermit or nomad? PMID- 2918162 TI - Relation between exertional ischemia and prognosis in mildly symptomatic patients with single or double vessel coronary artery disease and left ventricular dysfunction at rest. AB - The randomized multicenter trials indicate that survival in patients with coronary artery disease and left ventricular dysfunction is enhanced by surgical therapy compared with medical therapy. This beneficial effect of coronary bypass surgery was demonstrated in patients with either three vessel or left main coronary artery disease, but not in those with one or two vessel disease. To determine whether subgroups of mildly symptomatic patients with one or two vessel coronary artery disease and left ventricular dysfunction have an increased risk of death or cardiac events during medical therapy, 53 consecutive patients with angiographically defined one or two vessel disease and impaired left ventricular function (ejection fraction 20% to 40%) were studied by exercise electrocardiography (ECG) and rest and exercise radionuclide angiography. All but two patients had previous myocardial infarction, and all were asymptomatic or only mildly symptomatic during medical therapy. By univariate life table analysis, mortality during medical therapy was associated significantly with the ST segment response to exercise (p less than 0.05) and with both the exercise ejection fraction (p less than 0.05) and the magnitude of change in ejection fraction with exercise (p less than 0.005). In patients with an exercise ejection fraction greater than 30%, the probability of survival at 6 years was 97 +/- 3% (+/- SE) compared with a survival rate of 62 +/- 14% in the remaining subjects (p less than 0.005). Similarly, 6 year survival was 100% in patients whose ejection fraction increased from the value at rest but was only 74 +/- 10% in the remaining patients (p less than 0.005). Exercise capacity was not associated with survival.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918163 TI - Hypertensive hypertrophic cardiomyopathy or hypertrophic cardiomyopathy with hypertension? A study of 78 patients. AB - Hypertensive hypertrophic cardiomyopathy may be a distinctive cardiac condition resulting from hypertension. Alternatively, this disease may represent the coincidence of a common disease, hypertension, with a relatively rare cardiomyopathy. A consecutive series of patients with hypertrophic cardiomyopathy and hypertension were studied and compared with age- and gender-matched patients with cardiomyopathy alone. Thirty-nine patients were identified as having hypertension; they ranged in age from 31 to 84 years (average 60 +/- 13); 82% were greater than 50 years old; 18 (46%) were women. When these patients were compared with the age-matched group with hypertrophic cardiomyopathy alone, there were no clinical or electrocardiographic differences between the two groups. By echocardiography, the hypertensive and nonhypertensive groups had a similar incidence of systolic anterior motion (77 versus 64%, respectively), mitral annular calcification (31 versus 31%), septal thickness greater than 20 mm (56 versus 46%) and outflow tract gradient greater than 20 mm (59 versus 67%). A posterior wall thickness greater than 13 mm was more frequent in the hypertensive group (54%) compared with the nonhypertensive group (31%) (p = 0.02). The findings show that hypertrophic cardiomyopathy with associated hypertension is a disease of the elderly. But, with the exception of thicker walls, the clinical and echocardiographic features of the patients with hypertension were indistinguishable from those of the age-matched and, hence, elderly group of patients with cardiomyopathy without hypertension. These findings suggest that hypertension may make hypertrophy worse, but that it is not the primary cause of the cardiomyopathy. Thus, the condition might be better termed "hypertrophic cardiomyopathy with hypertension." PMID- 2918164 TI - Quantitative assessment of mitral regurgitation by Doppler color flow imaging: angiographic and hemodynamic correlations. AB - This study was performed to test the hypothesis that measurements of jet area by Doppler color flow imaging can predict the angiographic severity and hemodynamic consequences of mitral regurgitation. Doppler color flow imaging was performed in 47 patients undergoing cardiac catheterization and left ventriculography. The jet area was measured as the largest clearly definable flow disturbance in the parasternal and apical views, and expressed as the maximal jet area, the mean of the largest jet area (average jet area) in two views or as the ratio of these measures to left atrial area. Correlation of all Doppler color flow measurements with angiographic grades of mitral regurgitation were comparable, maximal jet area being closest at r = 0.76. A maximal jet area greater than 8 cm2 predicted severe mitral regurgitation with a sensitivity of 82% and specificity of 94%, whereas a maximal jet area less than 4 cm2 predicted mild mitral regurgitation with a sensitivity and specificity of 85% and 75%, respectively. All patients with an average jet area greater than 8 cm2 manifested severe mitral regurgitation. However, jet area measurements showed limited correlation with regurgitant volume and fraction (r = 0.55 and 0.62, respectively) for maximal jet area, and were not predictive of hemodynamic abnormalities, including those of pulmonary wedge pressure, stroke volume or ventricular volumes. Thus, in patients with mitral regurgitation, maximal jet area from Doppler color flow imaging provides a simple measurement that predicts angiographic grade, but manifests a weak correlation with regurgitant volume and does not predict hemodynamic dysfunction. PMID- 2918165 TI - Quantitative assessment of mitral regurgitation. PMID- 2918166 TI - Reassessment of valve area determinations in mitral stenosis by the pressure half time method: impact of left ventricular stiffness and peak diastolic pressure difference. AB - Estimation of the orifice area is of major importance in the timing of valve dilation or surgery in patients with mitral stenosis. Determination of the area has traditionally been accomplished at cardiac catheterization by the Gorlin equation. The valve area can also be estimated noninvasively with Doppler echocardiographic measurements of the pressure half-time, which is inversely proportional to the area. This method has gained widespread acceptance, but its accuracy has recently been questioned and factors other than reduction of orifice area appear to modify the pressure half-time. In the present study, the influence of left ventricular stiffness (defined as diastolic pressure rise per milliliter of mitral flow) and peak atrioventricular pressure difference on the pressure half-time was examined both in a hydraulic model and by review of data from 35 patients with mitral stenosis. Left ventricular stiffness less than 0.13 mm Hg/ml was considered normal. In the model study, the orifice area correlated only moderately with inverted pressure half-time (1/PHT) (r = 0.67). By multiple linear regression, inverted pressure half-time was shown to be dependent on valve area, chamber stiffness and peak pressure difference (R = 0.89), area and stiffness being most important (R = 0.85). In the clinical study, an increased ventricular stiffness was found in 22 of the 35 patients. The pressure half-time method overestimated the Gorlin-derived area by an average of 72% in these patients compared with only 10% in 13 patients with normal stiffness (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918167 TI - Pulsed Doppler evaluation of atrial mechanical function after electrical cardioversion of atrial fibrillation. AB - Full recovery of atrial mechanical activity may not occur immediately after successful electrical cardioversion of atrial fibrillation to sinus rhythm. To examine the time course of recovery of left atrial mechanical function, serial two-dimensional, M-mode and transmitral pulsed Doppler echocardiographic studies were performed in 21 patients after elective direct current cardioversion of atrial fibrillation of 3 weeks' to 24 months' duration (mean 5 months). Over 3 months of follow-up, there were significant increases in both peak A wave velocity (p less than 0.005) and percent atrial contribution to total left ventricular filling (p less than 0.005). Compared with values in a normal control population, peak A wave velocity and percent atrial contribution to total left ventricular filling did not return to normal until 3 weeks after cardioversion in patients who remained in sinus rhythm. Left atrial dimension also decreased over the follow-up period (p less than 0.05) in patients with persistent sinus rhythm. These results may have important implications in guiding the appropriate duration of anticoagulant therapy after cardioversion, and in clinically assessing the hemodynamic benefit of restoring sinus rhythm in an individual patient. PMID- 2918168 TI - Gender-related differences in cardiac response to supine exercise assessed by radionuclide angiography. AB - This study examines the recently reported gender differences in cardiac responses to exercise. The study group consisted of 192 men and 67 women with a low probability of coronary artery disease who underwent supine exercise radionuclide angiography. Men had a lower rest ejection fraction than that of women (0.63 versus 0.66, p = 0.02) and greater increases in ejection fraction with exercise (0.08 versus 0.02, p = 0.0001). The slope relating ejection fraction to metabolic equivalents of exercise (METs) was greater (p = 0.004) for men, even after adjustment for differences in rest ejection fraction and end-diastolic volume index. Compared with men, women had a smaller rest end-diastolic volume index (87 versus 97 ml/m2, p = 0.003) and a greater increase in end-diastolic volume index with exercise (6 versus -2 ml/m2, p = 0.002). The slope relating end-diastolic volume to METs was greater for women, even after adjustment for differences in rest end-diastolic volume index and peak work load. There are clear gender differences in the supine exercise response of ejection fraction and end diastolic volume that are not explained by differences in exercise capacity. PMID- 2918169 TI - Assessment of right atrial pressure-volume relations in patients with and without an atrial septal defect. AB - Assessment of the complex relations between pressure and volume in the right atrium has been hampered in the past by difficulties in the measurement of atrial volume. Accordingly, in the present study the dynamics of right atrial pressure volume relations were examined (with the use of an impedance catheter to measure right atrial volume) in patients with and without an atrial septal defect. Right atrial pressure and impedance volume were measured in 16 patients at the time of cardiac catheterization with the use of a multi-electrode impedance catheter to provide continuous, on-line, pressure-volume data. Eleven patients without evidence of an interatrial shunt were examined during normal respiration and during the Valsalva maneuver and contrasted with five patients with an atrial septal defect documented by oxygen saturation step-up and echocardiographic studies. Right atrial pressure-volume diagrams in patients without an atrial septal defect exhibited the normal figure eight pattern, with an A loop (atrial contraction) and a V loop (passive filling), corresponding to the A wave and V wave of right atrial pressure, respectively. During inspiration, mean right atrial pressure decreased and mean right atrial volume increased, consistent with augmented venous return. With the Valsalva maneuver, right atrial pressure increased and both right atrial stroke volume and mean right atrial volume decreased compared with baseline. Patients with an atrial septal defect demonstrated baseline pressure-volume diagrams similar to those of patients without an interatrial shunt. However, no change in mean right atrial volume occurred with either respiration or the Valsalva maneuver despite changes in right atrial pressure similar to those seen inpatients without an atrial septal defect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918170 TI - Predictors of inducible sustained ventricular tachyarrhythmias in patients with coronary artery disease. AB - To determine predictors of inducible sustained ventricular tachycardia or fibrillation by programmed electrical stimulation in patients with coronary artery disease and ventricular tachyarrhythmias, 14 clinical and angiographic variables were analyzed in 60 consecutive patients. All patients had angiographically documented coronary artery disease and symptomatic ventricular arrhythmias (sustained ventricular tachycardia in 21, ventricular fibrillation in 21 and nonsustained ventricular tachycardia in 18). Baseline programmed electrical stimulation while the patient was not taking antiarrhythmic drugs was performed with use of single, double and triple extrastimuli and burst pacing from two right ventricular sites. The variables analyzed were presenting arrhythmia; presence, frequency and complexity of ventricular ectopic activity on baseline 24 h electrocardiographic (Holter) monitoring; greater than or equal to 70% narrowing in either the left anterior descending, proximal left anterior descending, right coronary or circumflex coronary artery (independently assessed); single, double or triple vessel coronary disease; anterior, apical or inferior wall motion abnormalities; segmental dyskinesia and ejection fraction. Thirty-seven patients (62%) had inducible sustained ventricular tachycardia (rate greater than 100 beats/min, duration greater than 30 s or requiring cardioversion) and two patients (3%) had ventricular fibrillation induced. Eleven patients (18%) had nonsustained ventricular tachycardia (duration greater than or equal to 3 beats, less than 30 s) induced and 10 patients (17%) had no inducible arrhythmia (duration less than 3 beats). Multivariate stepwise logistic regression analysis identified three independent variables predictive of inducible sustained ventricular arrhythmias: sustained ventricular tachycardia as the presenting arrhythmia (p = 0.004), proximal left anterior descending artery lesion (p = 0.002) and anterior wall motion abnormality (p = 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918171 TI - Changes in spontaneous sinus node rate as an estimate of cardiac autonomic tone during stable and unstable ventricular tachycardia. AB - Changes in sinus node rate were measured as an estimate of reflex control of cardiac autonomic tone during 32 episodes of stable ventricular tachycardia (without loss of consciousness) and 21 episodes of unstable ventricular tachycardia (loss of consciousness requiring electrical cardioversion) in 32 patients without retrograde ventriculoatrial conduction. Sinus node rate was measured before induction of ventricular tachycardia (at 5 s intervals during tachycardia) and 5 s after termination of ventricular tachycardia. It increased from 85 +/- 12 beats/min to a maximum of 109 +/- 25 beats/min during stable ventricular tachycardia (p less than 0.001) and from 82 +/- 15 beats/min to a maximum of 105 +/- 34 beats/min during unstable ventricular tachycardia (p less than 0.001). During unstable ventricular tachycardia, the increase in sinus rate was more abrupt and was followed by a sharp decrease beginning before termination of the tachycardia and resulting in a slower rate after termination (56 +/- 15 beats/min) than before tachycardia (p less than 0.001). Stable ventricular tachycardia resulted in a continuous increase of sinus node rate, which remained higher after termination (102 +/- 15 beats/min) than before tachycardia (p less than 0.001). Autonomic mechanisms responsible for changes in sinus rate were evaluated by reinducing the ventricular tachycardia after beta-adrenergic blockade by propranolol in 10 patients. Intravenous propranolol (mean dose 11 +/- 4 mg) had no effect on the magnitude of increase in sinus rate (+18 +/- 6 beats/min before and +17 +/- 7 beats/min after propranolol).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918172 TI - Beneficial effects of long-term diltiazem treatment in dilated cardiomyopathy. AB - There is increasing evidence that chronic enhanced exogenous or endogenous catecholamine stimulation in patients with dilated cardiomyopathy may worsen hemodynamic status and prognosis. The cause of this deterioration may lie in myocellular calcium accumulation and microcirculatory disorders. In a prospective study, the calcium channel antagonist diltiazem was given to 22 patients with dilated cardiomyopathy (60 to 90 mg three times daily) in addition to conventional therapy of digitalis, diuretics and vasodilators. Twenty-five patients received the conventional therapy and served as historical controls. Eight additional patients who were not originally included in this control group received adjunctive diltiazem treatment after initially receiving conventional therapy alone. The three patient groups were similar in all hemodynamic and anamnestic features. Only patients with reduced myofibrillar volume fraction on myocardial biopsy were included in the trial, because they could be expected to show hemodynamic deterioration. The mean survival time was 29 months in the control group, whereas no patient in the diltiazem group died over a mean follow up period of 15.4 months (p less than 0.001). Mean left ventricular ejection fraction increased from 0.34 to 0.44 (p less than 0.001) and New York Heart Association functional class improved significantly in the diltiazem group and during the diltiazem period in the crossover patients, but deteriorated in the control group. The results suggest that adjunctive diltiazem treatment in dilated cardiomyopathy has beneficial effects on mortality, hemodynamics and symptoms. PMID- 2918173 TI - Combination of disopyramide and mexiletine for better tolerance and additive effects for treatment of ventricular arrhythmias. AB - The efficacy and tolerance of disopyramide and mexiletine used alone and in combination were studied in 21 patients with frequent (greater than or equal to 30/h) ventricular premature complexes. Ambulatory electrocardiographic monitoring was performed at baseline and during therapy with disopyramide alone, mexiletine alone and a combination of disopyramide and mexiletine. During single drug therapy, the dose of disopyramide was 602 +/- 152 mg/day and that of mexiletine was 738 +/- 144 mg/day. During combination therapy with smaller doses of disopyramide (524 +/- 134 mg/day) and mexiletine (652 +/- 146 mg/day), no patient had side effects. At baseline before therapy, the mean number of ventricular premature complexes per hour, was 608 +/- 757, of couplets per hour was 22.4 +/- 45.8 and of episodes of nonsustained ventricular tachycardia/24 h was 219.7 +/- 758.2. The mean number of ventricular premature complexes per hour was reduced to 156 +/- 217 with disopyramide alone, 188 +/- 298 with mexiletine alone and 76 +/- 144 with combination therapy (p less than 0.05 for combination therapy versus disopyramide or mexiletine alone; p = NS for disopyramide versus mexiletine). Individually, an effective regimen (greater than 83% reduction in ventricular premature complexes and abolition of nonsustained ventricular tachycardia) was found in 5 (24%) of 21 patients during therapy with disopyramide alone, in 3 (14%) receiving mexiletine alone and in 13 (62%) receiving combination therapy (p less than 0.05 for combination therapy versus disopyramide or mexiletine; p = NS for disopyramide versus mexiletine). Thus, the antiarrhythmic effects of disopyramide and mexiletine are additive.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918174 TI - Contrast two-dimensional echocardiography in congenital heart disease: techniques, indications and clinical utility. AB - Saline contrast echocardiography was performed in 889 children from June 1976 through February 1988. One-third of these studies were in postoperative patients. A patent foramen ovale was identified by finding right to left shunting on venous contrast injection in 37% of 127 children studied with a structurally normal heart. The incidence of such shunting was greater at younger ages (55% younger than 1 month versus 22% older than 1 month). In most patients with an atrial or ventricular septal defect, some right to left shunting was demonstrable. The technique was useful in distinguishing different forms of atrial septal defect and identifying muscular ventricular septal defects that were difficult to image directly. The technique was used in the catheterization laboratory to aid in the identification of congenital coronary artery fistulas and was diagnostic in two cases of pulmonary arteriovenous malformation. In patients with situs abnormalities, the technique was useful in identifying the systemic venous connections to the atria. Contrast echocardiography was also used in postoperative evaluations. The technique was useful in identifying patch leaks and residual defects after Senning, Mustard and Fontan operations, and after closure of atrial and ventricular septal defects. Most patients were found to have no superior vena cava obstruction by contrast echocardiography after the Senning or Mustard procedure. Contrast echocardiography continues to be a useful technique in the diagnosis of a wide spectrum of congenital heart disease, as well as in the postoperative evaluation of congenital heart surgery. PMID- 2918175 TI - Contrast echocardiography in the Doppler color flow imaging era. PMID- 2918176 TI - Doppler echocardiographic evaluation of right and left ventricular diastolic function in normal neonates. AB - Doppler echocardiograms of the tricuspid and mitral valves were recorded along with the electrocardiogram and respiration in 22 normal full-term neonates. A computer-interfaced digitizer pad was utilized to measure the following: peak E and A velocities (cm/s); E and A areas (the components of the total velocity-time integral in the early passive period of ventricular filling [E] and the late active period of atrial emptying [A], respectively) and the 1/3 area fraction (or the proportion of filling in the first 1/3 of diastole). All of the variables of right (tricuspid) versus left (mitral) ventricular filling were significantly different on the 1st day of life. Respective values were peak E velocity (cm/s) 44.6 +/- 10.0 (tricuspid) versus 53.2 +/- 9.3 (mitral), p less than 0.01; peak E/A ratio 0.84 +/- 0.14 versus 1.15 +/- 0.17, p less than 0.0001; E/total area 0.58 +/- 0.07 versus 0.63 +/- 0.05, p less than 0.005; E/A area ratio 1.05 +/- 0.23 versus 1.63 +/- 0.40, p less than 0.0001; 1/3 area fraction 0.31 +/- 0.04 versus 0.41 +/- 0.04, p less than 0.0001; peak A velocity (cm/s) 53.0 +/- 8.4 versus 47.6 +/- 5.8, p less than 0.05 and A/total area 0.57 +/- 0.09 versus 0.41 +/- 0.09, p less than 0.001; the mean heart rate (beats/min) was not significantly different: 121 +/- 8 versus 120 +/- 7. Most of the variables remained significantly different on the 2nd day of life, but the level of significance was the same or less for all measurements.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918177 TI - Pressure recovery distal to a stenosis: potential cause of gradient "overestimation" by Doppler echocardiography. AB - Doppler ultrasound is currently being widely applied to measure intracardiac pressure gradients noninvasively. In comparative invasive studies, it is generally assumed that pressure is effectively uniform distal to the stenosis. As the poststenotic jet expands, however, its velocity decreases, and pressure is recovered to the extent permitted by turbulence, so that the measured gradient will be lower if the distal catheter is positioned downstream from the vena contracta. This can lead to apparent Doppler "overestimation" of the pressure gradient because of this phenomenon of pressure recovery. This study demonstrates that pressure recovery can be important in a variety of clinical settings studied by in vitro models. Although most prominent in streamlined tunnels modeled after the obstruction in patients with hypertrophic cardiomyopathy, these effects are important even for central stenoses at physiologic flow rates. Because precise catheter position is not always known or controlled, these findings suggest an important advantage for Doppler gradient estimation, because it provides the maximal gradient at the vena contracta, which determines the load on the proximal chamber. PMID- 2918179 TI - Contraction pattern within ischemic-infarct zones in acute myocardial infarction. PMID- 2918178 TI - Evolution of the temporal contraction sequence after acute experimental myocardial infarction. AB - The effect of infarct maturation on the temporal sequence of contraction within infarct zones has not previously been described. Accordingly, the time-varying pattern of contraction within ischemic/infarct zones was studied with use of cross-sectional echocardiography in 17 dogs at 10 min to 6 weeks after acute experimental myocardial infarction. Left ventricular short-axis images were digitized from end-diastole to end-systole and endocardial fractional radial change along 36 evenly spaced rays was calculated. The circumferential extent of dyskinesia and the number of rays that exhibited maximal dyskinesia were determined for each decile of the normalized contraction sequence. Between 10 min and 1 week after infarction, the greatest circumferential extent of dyskinesia occurred between the 3rd and 4th deciles of the normalized contraction sequence. However, as the infarct matured, the greatest spatial expanse of dyskinesia was noted to occur progressively earlier in the contraction sequence (second decile at 6 weeks), and the extent of mid- to late-systolic dyskinesia decreased markedly. Whereas end-systolic dyskinesia was present in 30% to 50% of ischemic/infarct zone rays from 10 min to 48 h, end-systolic dyskinesia was no longer observed at 6 weeks. Similarly, the maximal amplitude of dyskinesia was most commonly observed during midsystole from 10 min to 48 h, but occurred progressively earlier as the infarct matured, falling during the first decile at 6 weeks after infarction. These data suggest that maximal circumferential extent and amplitude of dyskinesia occur progressively earlier in the systolic contraction sequence as the infarct matures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918180 TI - Demonstration of increased myocardial lipid with postischemic dysfunction ("myocardial stunning") by proton nuclear magnetic resonance spectroscopy. AB - Histopathologic studies have demonstrated accumulation of lipid droplets in myocardium subjected to greater than or equal to 6 h of ischemic insult. Proton nuclear magnetic resonance (NMR) spectroscopy can provide a noninvasive means to evaluate changes in tissue lipid and, potentially, to characterize the ischemic insult. To determine whether lipids accumulate with a brief ischemic insult, myocardial lipid content was evaluated by 1H NMR spectroscopy of ex-vivo samples from seven dogs in a model of postischemic dysfunction created by 15 min of left anterior descending coronary artery occlusion followed by 3 h of reperfusion. Regional myocardial function was assessed by measuring segment length shortening with use of a pair of ultrasonic crystals placed in the ischemic zone and in the control zone. During the occlusion, all dogs had significant ischemia of the occlusion zone as measured by radiolabeled microspheres (0.08 +/- 0.08 versus 0.88 +/- 0.09 ml/g per min for the control zone), and all dogs developed systolic stretching of the ischemic zone segment. Myocardial lipid content was significantly elevated in the samples from the coronary occlusion zone (p less than 0.02). The increase in lipid signal may result from the ischemia-induced decrease in beta oxidation and resultant accumulation of fatty acyl esters (for example, fatty acids, triglycerides and acylcarnitines). In conclusion, this study shows that myocardium subjected to a brief (approximately 15 min) coronary occlusion followed by 3 h of reperfusion demonstrates a significant increase in NMR-detectable lipid content. PMID- 2918181 TI - Sustained nonoxidative glucose utilization and depletion of glycogen in reperfused canine myocardium. AB - Ischemically injured reperfused myocardium is characterized by increased 18F fluorodeoxyglucose uptake as demonstrated by positron emission tomography. To elucidate the metabolic fate of exogenous glucose entering reperfused myocardium, D-[6-14C] glucose and L-[U-13C] lactate were used to determine glucose uptake, glucose oxidation and the contribution of exogenous glucose to lactate production. The pathologic model under investigation consisted of a 3 h balloon occlusion of the left anterior descending coronary artery followed by 24 h of reperfusion in canine myocardium. The extent and severity of myocardial injury after the ischemia and reperfusion were assessed by histochemical evaluation (triphenyltetrazolium chloride and periodic acid-Schiff stains). Thirteen intervention and four control dogs were studied. The glucose uptake in the occluded/reperfused area was significantly enhanced compared with that in control dogs (0.40 +/- 0.14 versus 0.15 +/- 0.10 mumol/ml, respectively). In addition, a significantly greater portion of the glucose extracted immediately entered glycolysis in the intervention group (75%) than in the control dogs (33%). The activity of the nonoxidative glycolytic pathway was markedly increased in the ischemically injured reperfused area, as evidenced by the four times greater lactate release in this area compared with the control value. The dual carbon labeled isotopes showed that 57% of the exogenous glucose entering glycolysis was being converted to lactate. Exogenous glucose contributed to greater than 90% of the observed lactate production. This finding was confirmed by the histochemical finding of sustained glycogen depletion in the occlusion/reperfusion area. The average area of glycogen depletion (37%) significantly exceeded the average area of necrosis (17%). These data demonstrate enhanced and sustained activity of the nonoxidative glycolytic pathway after a prolonged occlusion with reperfusion in canine myocardium. Because glycogen stores remain depleted, exogenous glucose becomes an important myocardial substrate under these pathologic conditions. PMID- 2918182 TI - The need for clarification of percent risk reduction data in clinical cardiovascular trial reports. PMID- 2918183 TI - Cross-reactivity between penicillins and cephalosporins: clinical and immunologic studies. AB - Nineteen well-characterized penicillin-allergic patients were investigated for their sensitivity to cephalosporins containing potentially cross-reactive side chains. All patients were administered cephamandole parenterally and, if this was tolerated, a course of oral cephaloridine was administered. Only two patients responded to the cephamandole; none of the remaining patients reacted to cephaloridine. Benzylpenicilloyl RAST-inhibition studies with sera from three subjects who had not reacted to the cephalosporins demonstrated that cephamandole linked to proteins was capable of recognizing benzylpenicilloyl-specific IgE antibody. It is concluded that consideration of side chain structures can help to predict possible cross-reactions between penicillins and cephalosporins, but carefully controlled challenge tests are advisable before penicillin-allergic patients are treated with cephalosporins. In relation to cross-reacting potential, in vitro experimental studies are difficult to interpret and may in some circumstances overestimate the risk. PMID- 2918184 TI - Therapeutic effect and titers of the specific IgE and IgG antibodies in patients with sea squirt allergy (Hoya asthma) under a long-term hyposensitization with three sea squirt antigens. AB - Hyposensitization therapy with each of three sea squirt antigens, Gi-rep (molecular weight [MW] 106,000), Ei-M (MW 22,800), and DIIIa (MW 9980), have succeeded in 72%, 90%, and 36% of patients with sea squirt allergy, respectively, within the first year, and the effect has been maintained during subsequent 4 year maintenance therapy. All available sera from some of the hyposensitized patients were also examined for IgE and IgG titers against the most effective therapeutic antigen, Ei-M, and it was revealed that the Ei-M-specific IgG titer increased rapidly in the successfully hyposensitized patients, regardless of the therapeutic antigen used, except for a few patients. Furthermore, the high specific IgG titer, as well as the therapeutic effect, was maintained during the subsequent maintenance therapy. No such increase in the specific IgG titer was detected in all unsuccessfully hyposensitized patients. In contrast, the Ei-M specific IgE titer was practically unchanged in all allergic patients, independent of the therapy. Therefore, the effect of the hyposensitization therapy was closely dependent on the induction of the specific IgG capable of competing with the specific IgE for a certain asthma-inducing antigen, like DIIIa. The apparently low therapeutic efficiency of DIIIa was attributed to its relatively low immunogenicity to induce the specific IgG. PMID- 2918185 TI - The effect of theophylline and enprofylline on the late cutaneous response to antigen and compound 48/80. AB - Theophylline and enprofylline have been demonstrated to reduce mast cell-mediator release, inhibit polymorphonuclear leukocyte activation, and have been reported to reduce the late bronchial response to antigen. The effects of theophylline and enprofylline on the late cutaneous response (LCR) to compound 48/80 and antigen were studied in 29 patients enrolled in a placebo-controlled, double-blind study of the effect of the xanthines in mild asthma. Skin testing to a common environment allergen and compound 48/80 was performed during a baseline period and in the second phase of the study after stable drug levels were achieved, at least 6 weeks later. During baseline, the mean immediate wheal diameter (IWD) with antigen was 15.7 mm +/- 0.5, resulting in 27/29 LCRs with a mean wheal diameter of 37.1 mm +/- 5.2. The mean IWD with compound 48/80 was 16.1 mm +/- 0.7, resulting in 26/29 LCRs with a mean wheal diameter of 19.6 mm +/- 2.8. Repeat skin testing during treatment revealed no statistically significant changes in the LCR elicited by antigen or 48/80 in any of the treatment groups. There was little correlation between the size of the immediate wheal produced by antigen or 48/80 and the resulting size of the late response (r = 0.174 to 0.519). However, for the same IWD, the resulting late response was smaller with 48/80 than with antigen (p = 0.003). We conclude that (1) theophylline and enprofylline have no effect on the LCR to 48/80 and antigen and (2) for equivalent immediate wheal sizes, the resulting late response is smaller with 48/80 than with antigen. PMID- 2918186 TI - Cross-allergenicity in the legume botanical family in children with food hypersensitivity. AB - Sixty-nine patients with one or more positive prick skin tests to legumes (peanut, soybean, green bean, pea, and lima bean) were evaluated for food hypersensitivity with in-hospital oral food challenges. Of the 280 prick skin tests to legumes performed, 130 were positive. Forty-three positive food challenges occurred in 41 patients. The prevalence of legume allergy was not statistically different in those patients (N = 36) with two or more positive legume prick skin test (64% positive) compared to those patients (N = 33) with only one positive legume prick skin test (55% positive; p greater than 0.10). Even in this selected patient population, only two patients had symptomatic hypersensitivity to two legumes. Among patients with a positive prick skin test to peanut (N = 60), the mean wheal size was larger in patients with a positive versus a negative oral food challenge to peanut (p less than 0.001). Results of oral food challenges demonstrate that clinically important cross-reactivity to legumes in children is very rare. Clinical hypersensitivity to one legume does not warrant dietary elimination of all legumes. Results of prick skin tests should not be used to determine prolonged food restriction diets. PMID- 2918187 TI - Serum immunoglobulin E levels in patients with primary biliary cirrhosis. AB - Serum IgE levels were measured in 22 symptomatic adults with primary biliary cirrhosis (PBC) and 19 asymptomatic female adults with positive serum mitochondrial antibody tests. Control populations included 45 adult patients with chronic liver disease consisting of autoimmune chronic active hepatitis (N = 15), alcoholic liver disease (N = 15), or miscellaneous cholestatic liver disorders (N = 15), and 87 healthy adult hospital personnel. Fourteen of 22 (64%) patients with PBC had low (less than 10 KU/L) or undetectable serum IgE levels, compared to 12 of 45 (27%) control patients with liver disease (p less than 0.005) and 39 of 87 (45%) healthy control subjects (p = 0.09). Low serum IgE levels were also found in most (13 of 19 patients, 68%) asymptomatic individuals with positive serum mitochondrial antibody tests (p less than 0.005 and p less than 0.05 versus liver disease and healthy control subjects, respectively). In vitro IgE production by peripheral blood mononuclear cells after pokeweed mitogen stimulation was determined in eight patients with PBC and in eight healthy control subjects. After pokeweed mitogen stimulation, one of three, patients with PBC compared to four of four healthy control subjects with detectable levels of serum IgE, produced sufficient amounts of IgE to be detected in culture supernatants. Neither the five patients with PBC nor the four healthy control subjects with undetectable serum IgE levels produced sufficient amounts of IgE in vitro to be detected in our assay system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918189 TI - Inflammation in asthma. Kenilworth, New Jersey, December 11, 1987. Proceedings. PMID- 2918188 TI - Seasonal variation in specific IgE antibodies of grass-pollen hypersensitive patients depends on the steady state IgE concentration and is not related to clinical symptoms. AB - To evaluate parameters that determine the serum titer of specific antiallergen IgE antibodies, we graded the clinical symptoms of 78 grass-pollen hypersensitive patients during two consecutive seasons, while serum total and specific antigrass pollen IgE antibodies were titrated every 2 weeks. Correlation studies of clinical symptoms, grass-pollen counts, and specific IgE antibodies demonstrated that (1) bronchial asthma and nasal symptoms cannot be predicted on the basis of preseasonal IgE titers, (2) clinical symptoms are not related to seasonal antigrass-pollen IgE antibodies, (3) antigrass pollen and total IgE antibodies are not directly dependent on the air pollen point concentration, (4) increase in specific IgE antibodies during the pollen season is strongly correlated to preseasonal specific IgE titers, and (5) individual fluctuations of specific IgE antibody titers during the pollen season are proportional to preseasonal specific IgE titers. These findings suggest that titration of serum-specific IgE antibodies is of little use in predicting or monitoring the clinical symptoms of grass-pollen hypersensitive patients, since IgE titers strongly depend on individual immune responsiveness. PMID- 2918190 TI - Treatment of an influenza A outbreak in a teaching nursing home. Effectiveness of a protocol for prevention and control. AB - The safety and efficacy of current ACIP guidelines for the prevention and control of influenza in nursing home populations are uncertain. An outbreak of influenza A/Sichuan (H3N2) in a teaching nursing home during 1988 gave us the opportunity to evaluate the effectiveness of an influenza vaccination and amantadine prophylaxis protocol. Over 13 days, 12 of 60 residents developed influenza. Prior influenza vaccination had been given to 94% of the residents. Protection from infection occurred in those tested who had antibody levels greater than or equal to 1:16 to the A/Leningrad (H3N2) antigen contained in the standard 1987-88 trivalent vaccine. However, five of 17 vaccinated residents who were tested had antibody levels less than or equal to 1:16 at the start of the outbreak. Amantadine (less than or equal to 100 mg/day) was given to all but one resident starting on the third day of the outbreak, and to employees starting on the sixth day of the outbreaks. Seven residents developed illness after the start of amantadine, although amantadine appeared to ameliorate their symptoms. Although amantadine was generally well tolerated by residents, employees receiving amantadine identified a high incidence of side effects and only 44% of employees took at least 70% of the prescribed amantadine. In our opinion, early detection and protocol-directed intervention probably abated a more severe influenza outbreak. Therefore we support existing recommendations that formal nursing home policies be established to ensure that residents and employees receive annual influenza vaccine and that chemoprophylaxis be used when outbreaks of influenza A are suspected. PMID- 2918191 TI - Total hip replacement in patients aged 80 years and older. AB - Total hip replacement was performed in 27 patients aged 80 years and older. In the early postoperative period, medical complications occurred in 13 patients and arthroplasty-related complications in 5 patients. At the time of the follow-up, after an average of 31 months, there was one case of acetabular cup loosening, which was revised. Twenty of 22 patients were free from pain at rest, and the social function of the patients had remained almost unchanged. PMID- 2918192 TI - Impact of mild to moderate hearing loss on mental status testing. Comparability of standard and written Mini-Mental State Examinations. AB - Mild to moderate hearing loss has been hypothesized to decrease performance on verbally-administered cognitive tests as an artifact of testing. To evaluate this hypothesis, we conducted a randomized trial of a written version of the Mini Mental State Examination (MMSE), a cognitive screening instrument which, in its standard form, is primarily verbally administered. After baseline standard MMSE testing, 71 outpatients with Alzheimer's type dementia, 39 of whom (55%) had mild to moderate hearing deficits, and 32 of whom (45%) had normal hearing, were randomly assigned to receive either a written or standard MMSE. Hearing-impaired patients exhibited lower standard MMSE scores than hearing-unimpaired patients at baseline (P = .005). Contrary to expectation, however, on experimental administration, written MMSE scores were somewhat lower than standard MMSE scores in hearing-impaired patients (P not significant). Furthermore, written MMSE scores were slightly higher than standard MMSE scores in hearing-unimpaired patients (P not significant). These results suggest that the diminished cognitive performance associated with mild to moderate hearing loss is not necessarily an artifact of cognitive testing. In addition, these results provide preliminary evidence that a written MMSE is comparable to the standard MMSE and, thus, deserves further consideration for cognitive screening of profoundly hearing impaired individuals. PMID- 2918193 TI - Air-fluidized bed treatment of nursing home patients with pressure sores. AB - There are no large studies on long-term treatment of nursing home patients with pressure sores. A 4-year experience of treating 95 nursing home patients on air fluidized beds was reviewed. Treated patients were elderly (median age 73 years) and neurologically impaired (79% with dementia, cerebral vascular accident, or anoxic encephalopathy). The index pressure sores (deepest truncal sore for each patient) were large (median surface area 35.3 cm2) and commonly located on the sacrum (41%) and trochanters (38%). Only 13 of 95 (14%) index sores healed completely, and only two small sores healed in less than 30 days. No others treated less than 30 days had greater than or equal to 50% reduction in sore surface area. Patients were grouped according to whether or not treatment was less than 30 days, and for those treated greater than or equal to 30 days, according to whether or not greater than or equal to 50% reduction in sore surface area occurred. None of the easily measured patient characteristics examined were associated with longer or more successful treatment. These results indicate that although air-fluidized beds can be used to treat pressure sores successfully, even in severely debilitated nursing home patients, no simple criteria can be used to predict which patients will benefit from this treatment. Because long periods of time are necessary for treatment [median trial length 79 days and 17 of 95 (18%) trials greater than 180 days], substantial patient-care expenditures result.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918194 TI - Use of the Functional Assessment Inventory to distinguish among the rural elderly in five service settings. AB - This replication study further supports the hypothesis that the Functional Assessment Inventory (FAI) can reliably distinguish between the elderly in different service settings. The five settings studied include a state mental health facility, a nursing home, a visiting nurse service, a senior center, and a control group of well elderly. The inclusion of the home care and control groups in this study provide new tests of the applicability of the FAI. The sample consisted of 125 elderly individuals with 25 subjects in each of the five groups. The FAI questionnaire was administered to the subjects and/or an informant when necessary. Results of a multivariate analysis of variance (MANOVA) revealed that the more functionally impaired individuals were utilizing the more care-intensive settings. The FAI identified three distinct "cluster groups": an institutional cluster (state mental health facility and nursing home), a home care cluster (visiting nurse service), and a community cluster (senior center and control group). Analysis of the subscale scores reveals discrete differences between each of the groups. Implications of the study findings are discussed. PMID- 2918195 TI - History-taking in the elderly with and without cognitive impairment. How useful is it? AB - To assess the usefulness of interviewing older adults with cognitive impairment, we analyzed data from the NIMH Epidemiologic Catchment Area Study. People aged 65 and older with cognitive impairment were twice as likely as age-matched unimpaired elders to report sufficient symptoms of psychiatric disorders to qualify for a current diagnosis (16% vs 7%), and were also more likely to qualify for a lifetime diagnosis (25% vs 15%). We considered whether this excess could be due to random responses by the impaired, but found the rank order of their symptoms very similar to that of the unimpaired. Although dementia is thought to affect recent more than remote memory, the impaired were no less likely than the unimpaired to report disorders of recent onset. We also compared the cognitively impaired and unimpaired with respect to their reliability as assessed by reinterview one year later and found no significant difference. We conclude that there is no reason to believe that the excess of disorders in the mildly impaired is an artifact caused by their poorer performance as respondents. Interviewing the elderly person with cognitive impairment is a useful way of discovering concurrent disorders that may be treatable. PMID- 2918197 TI - Hepatic dementia or acquired hepatocerebral degeneration. PMID- 2918196 TI - Post-poliomyelitis sequelae in the elderly. PMID- 2918198 TI - Timolol side effects and inadvertent overdosing. AB - The case reports demonstrate that significant and potentially dangerous side effects from timolol maleate occur as a result of inadvertent overdosing. Because many glaucoma patients are elderly and vision is frequently impaired, overdosing may be the mechanism of side effects in many patients especially the elderly. A simple dropper that would withdraw only one drop and deliver the same would resolve this problem. PMID- 2918199 TI - Geriatric medicine in the United States. The current activities of former trainees. AB - To improve the health care received by frail older persons, an effort has been made in the United States to increase the number of physicians trained in geriatric medicine and geropsychiatry. The goal of training has been to create leaders in education, research, and patient care. To assess the progress of this effort, we surveyed physicians (284 in geriatric medicine and 91 in geropsychiatry) who graduated from U.S. geriatrics fellowship programs. Responses were obtained from 224 medicine (79% response) and 59 psychiatry fellows (65% response). Sixty-five percent of former geriatric medicine fellows report spending 10% or less time on teaching; 44% report doing no research, and 44% report spending more than half their time in patient care. Compared to other primary care specialties, the geriatricians reported caring for larger proportions of older patients and spending more time per patient visit. However, their role in teaching, research, and long-term care is minimal. PMID- 2918200 TI - Whither geriatrics faculty development? PMID- 2918201 TI - How should we treat third parties? PMID- 2918202 TI - Reserpine for hypertension. PMID- 2918203 TI - Quality of life in geriatric hypertension. PMID- 2918205 TI - Reprise on Comprehensive Geriatric Assessment. PMID- 2918204 TI - Measuring the volume of pressure sores. PMID- 2918206 TI - Somatosensory evoked potentials in infants and children. PMID- 2918207 TI - Intraventricular interferon treatment for subacute sclerosing panencephalitis. AB - Three children with subacute sclerosing panencephalitis (SSPE) were treated with alpha-interferon. Medication was administered via an Ommaya reservoir into the cerebral ventricular system over a period of 13 to 24 months in increasing amounts up to 1.0 x 10(6) IU twice weekly. Mild clinical improvement in two children and a stable course in the third were associated with improvement of electroencephalographic recordings in all patients and a decrease in antimeasles antibodies in the cerebrospinal fluid of two. The small number of patients does not enable us to determine whether this course was the natural history of SSPE in our patients or whether it was induced by treatment, yet it seems that intraventricular interferon treatment can modify the course of SSPE. PMID- 2918208 TI - Interictal sharp EEG transients in neonatal seizures. AB - This study describes the differences between several quantifiable variables that characterize interictal sharp EEG transients (SETS) recorded from neurologically ill neonates with proven electrographic seizures and a comparison group of apparently neurologically well babies with no known seizures. The abundance (number of sharp EEG transients per ten minutes), waveform morphology, repetitive behavior, and spatial distribution of SETS provide interpretive guidelines that help discriminate between these two patient populations. PMID- 2918209 TI - Megalencephaly in sudden infant death syndrome. AB - The fresh brain weights of 79 infants with sudden infant death syndrome (SIDS) were tabulated and compared with expected "normal" brain weights. The series included 47 males and 32 females. Their ages ranged from 8 days to 16 months with a median of 2.5 months. The weights of all these brains were above the 50th percentile for age, and 64 of 79 brains (81%) were above the 95th percentile, including 15 (19%) at or above the 99.9th percentile. The ratio of the brain stem plus cerebellum weight to the whole brain weight of 93 formalin-fixed brains from victims of SIDS showed that the cerebrum was disproportionately heavier in most cases. No gross or microscopic evidence of cerebral edema was noted to account for the heavier weight. The significance of these findings is debatable. The increase in brain weight was less obvious in infants younger than 1 month of age but accelerated after that age. The brain weights of infants with SIDS may represent the really "normal" weights, since these patients were not known to be ill prior to death. If the brain weights of SIDS infants are really heavier than "normal," the possibility must be considered that disproportionately rapid growth of the brain during early infancy may be detrimental to the neural control of the cardiorespiratory system. PMID- 2918210 TI - Benign nocturnal childhood occipital epilepsy: a new syndrome with nocturnal seizures, tonic deviation of the eyes, and vomiting. AB - An epileptic syndrome of benign nocturnal childhood occipital epilepsy with excellent prognosis is described. The syndrome is characterized by a clinical ictal triad of nocturnal seizures, tonic deviation of the eyes, and vomiting. There may be marching to involve the head and limbs, ending with a generalized tonic-clonic seizure. Consciousness is usually, but not invariably, disturbed. Infrequent daytime fits may develop one to two years after remission of the nocturnal seizures. Age of onset is usually from 3 to 5 years. Both sexes are involved. There is no family history of epilepsy or migraine. No definite causative factor was detected. The frequency of the seizures is very low with two children having only solitary ones. The interictal electroencephalographic features consist of repetitive occipital spike and slow wave complexes that are induced by closed eyes and darkness and are inhibited by open eyes and fixation with visual cues. It is proposed that this is a new idiopathic age-related-onset syndrome of the localization-related epilepsies. PMID- 2918211 TI - Neural defects in Jarcho-Levin syndrome. AB - Neuropathologic examination of two autopsied patients with Jarcho-Levin syndrome showed no pathologic changes in the brain, spinal cord, or nerve roots of one and diastematomyelia of the thoracolumbar spinal cord in the other. The abnormalities of the spinal cord in one of our patients and in another patient described in the literature establish neural defects as a component of the Jarcho-Levin syndrome. PMID- 2918212 TI - Eclampsia: a pediatric neurologic problem. AB - Eclampsia is a syndrome of hypertension, proteinuria, edema, and neurologic manifestations such as seizures, focal deficits, or blindness occurring during pregnancy, mainly in primigravidas. Although it is not seen often in the pediatric population, it occurs with greater frequency among pregnant patients under the age of 15 than in the general population. Serious sequelae can be prevented with prompt and adequate treatment, including termination of pregnancy. PMID- 2918213 TI - Pigmented, lipid-laden histiocytes in the central nervous system in chronic granulomatous disease of childhood. AB - In addition to granulomas, infiltrates of pigmented, lipid-laden histiocytes are a consistent morphologic finding in visceral organs of the reticuloendothelial system in patients with chronic granulomatous disease. We report a case with widespread meningeal and focal brain stem infiltrates of these distinctive histiocytes. The noninfectious involvement of the central nervous system in chronic granulomatous disease may be greater than previously recognized and related to the role of the CNS in the reticuloendothelial system. PMID- 2918214 TI - Foot pain in a diabetic patient. PMID- 2918216 TI - Adult onset of idiopathic inflammatory myopathies--therapy and prognosis. PMID- 2918215 TI - Acute gallbladder disease in the critical care patient. PMID- 2918217 TI - The nature and evaluation of cancer pain. PMID- 2918218 TI - Confidentiality--a physician's tool for effective medical treatment. PMID- 2918219 TI - Immunoelectron microscopic localization of laminin, type IV collagen, and type III pN-collagen in reticular fibers of human lymph nodes. AB - We studied the ultrastructural distribution of laminin, type IV collagen, and the amino terminal pro-peptide of type III collagen (type III pN-collagen) in normal human lymph nodes. After fixation with freshly prepared 4% paraformaldehyde mixed with 0.1% glutaraldehyde, cryoultramicrotomy proved to preserve the antigenicity of these proteins better than embedding in Lowicryl K4M. Sections were treated with rabbit antibodies against the 7S domain of human type IV collagen, the fragment P1 of human laminin, and the amino terminal pro-peptide of human type III pro-collagen, followed by anti-rabbit IgG conjugated to 10-nm colloidal gold. Laminin and type IV collagen were seen in the basement membrane structures of the blood vessels and in the walls of sinuses. The amorphous material between the collagenous fibers in locations corresponding to reticular fibers also contained laminin and type IV collagen. The amino terminal pro-peptide of type III pro collagen was present in the collagenous fibers in reticular fibers and in the walls of blood vessels and sinuses. Therefore, a significant number of the type III collagen molecules in these fibers must have retained their amino terminal pro-peptide. These results indicate that the basement membrane proteins laminin and type IV collagen are genuine components of reticular fibers, as suggested earlier by immunohistochemical studies at the light microscopic level. PMID- 2918220 TI - Intracellular topography of glycine-extended pro-gastrin-processing intermediates in human antral mucosa: an electron-microscopic immunocytochemical study. AB - To identify and characterize the subcellular topography of glycine-extended pro gastrin-processing intermediates (G-Gly) in human antral mucosa, we performed an electron microscopic immunocytochemical study using region-specific antisera generated against the synthetic peptide, Tyr-Gly-Trp-Met-Asp-Phe-Gly (GL7), and C terminal-specific anti-gastrin antisera. As has been previously reported, G-cells contained both electron-dense and electron-lucent granules, with a range of intermediate forms. Gastrin immunoreactivity was demonstrated in almost all granules of each type, whereas anti-GL7 antisera immunostained chiefly electron dense granules. The relative ratio of GL7/gastrin granules varied among different cells but was approximately 1:10 on average. Other cytoplasmic organelles were devoid of specific labeling for GL7 or gastrin. As we have assumed that G-Gly serves as the immediate precursor for each molecular form of gastrin, electron dense granules with high labeling for GL7 are regarded as the principal site for conversion of G-Gly to gastrin. This speculation supports many previous reports that electron-dense granules are immature and that the granules become less electron-dense with maturation. PMID- 2918221 TI - Alpha-smooth muscle actin, a differentiation marker of smooth muscle cells, is present in microfilamentous bundles of pericytes. AB - alpha-Smooth muscle (alpha-sm) actin, an isoform typical of smooth muscle cells (SMC) and present in high amounts in vascular SMC, was demonstrated in the cytoplasm of pericytes of various rat and human organs by means of immunocytochemistry at the electron microscopic level. In SMC and pericytes, alpha-sm actin was localized in microfilament bundles, strengthening the assumption that it is the functional isoform in these cell types and supporting the assumption that pericytes exert contractile functions. PMID- 2918222 TI - Heterogeneity of catalase staining in human hepatocellular peroxisomes. AB - Hepatocellular peroxisomes stained for catalase activity have different electron densities. When measured by scanning transmission electron microscopy, density is inversely linear to diameter. We investigated whether this phenomenon is the result of a staining artifact that reflects more efficient diffusion of substrate into smaller peroxisomes (higher surface-to-volume ratio), or of differences in endogenous enzymatic activity. Measurements of optical density show that the amount of reaction product is proportional to the diaminobenzidine concentration in the medium; this is not the case for H2O2. Modifying the concentration of both substrates does not alter the heterogeneous staining pattern. Heterogeneity persists when the reaction is slowed by inhibitors or when diffusion takes place before the reaction, and in preparations that have not been subjected to cytochemical staining. These data show that catalase activity is different in individual peroxisomes and that the staining differences are not a consequence of variations in substrate diffusion. Some implications of this conclusion are discussed. PMID- 2918223 TI - In situ hybridization using PEG-embedded tissue and riboprobes: increased cellular detail coupled with high sensitivity. AB - We describe a procedure for preparing tissue sections by embedding in polyethylene glycol for subsequent in situ hybridization analysis using single stranded RNA probes. Improved tissue morphology is obtained as compared to frozen sections, and the embedding procedure is milder and faster than paraffin embedding. Sections as thin as 2 microns are readily cut from PEG-embedded brain tissue. A simplified hybridization protocol (Clayton et al.: Neuron 1:249, 1988) supports the detection of even low-abundance brain mRNAs (less than or equal to 10(-4) fractional mRNA mass). By employing high stringency washes in place of ribonuclease treatment after hybridization, cell RNA is retained for cresyl violet staining, and high signal:noise ratios are achieved. Solutions to problems with section mounting and adherence to glass slides are presented. The combination of improved morphology, high signal levels, and relative simplicity should make this procedure useful in a variety of applications. PMID- 2918224 TI - Antigen presentation abrogated in cells expressing truncated Ia molecules. AB - Oligonucleotide site-directed mutagenesis was used to introduce a premature stop codon in wildtype A beta k and A alpha k cDNA clones to create truncated A beta k and A alpha k molecules lacking the cytoplasmic domain. Transfected B lymphoma cells expressing an I-Ak molecule with a truncated beta-chain or with truncated alpha- and beta-chains showed profound defects in two Ia-related functions: Ia restricted Ag presentation and intracytoplasmic signaling. The ability of these transfected cell lines to activate autoreactive T hybrids was markedly impaired whereas loss of Ag presentation to nominal Ag-specific T hybrids was more subtle. Ia-mediated transmembrane signaling as measured by PKC translocation from cytosol to nucleus after stimulation with anti-Ak antibody was greatly affected by truncation of the A beta and A alpha cytoplasmic domains. These results indicate an important role for the highly conserved cytoplasmic domain in Ia-mediated responses. PMID- 2918225 TI - Modulation of F1 cytotoxic potentials by graft-vs-host reaction. Cooperative non H-2- and H-2D region-gene control of F1 natural resistance to graft-vs-host reaction-associated immunosuppression. AB - Our previous study revealed that in F1 mice raised by crossing C3H/He or AKR/J mice with various H-2-congenic B10-series strains, parental H-2k spleen cells (SC) could not induce the graft-vs-host reaction (GvHR)-associated immunosuppression (GAIS). We also elucidated that a limited number of non-H-2 genes of parental C3H/He or AKR/J mice that had been incorporated into the F1 hybrids determined the F1 resistance to the GAIS, and the present study was done to explore the mechanism implicated in this type of F1 resistance to GAIS. SC from B10.AL mice carrying an rH-2 (K:k I:k S:k D:d) haplotype but not SC from H 2K B10.BR (k k k k) mice induced GAIS of in vitro CTL responses to third-party alloantigens in H-2k/d (C3H/He x B10.D2)F1 recipients mice. Further, SC from H 2k/a (C3H/He x B10.A)F1 mice carrying heterozygous C3H/B10 non-H-2 background but not SC from the same H-2k/a (B10.BR x B10.A)F1 mice but carrying homozygous B10/B10 background induced GAIS in H-2k/d (C3H/He x B10.D2)F1 recipients. Although C3H/He-, B10.BR-, and C3H.OH (d d d k)-SC were incapable of inducing GAIS in (C3H/He x B10.D2)F1 (k/d k/d k/d k/d) recipients, they were all good inducers of GAIS in (C3H.OH x B10.BR)F1 (d/k d/k d/k k/k) recipients. Exactly the same pattern of co-operative non-H-2 AKR and H-2D region-gene control of GAIS was observed on GvHR induced in H-2k/d (AKR/J x B10.D2)F1 recipients. These results suggest that the non-H-2 genes of C3H/He or AKR/J strain inhibit the functional expression of certain antigenic determinant(s) when it is encoded by heterozygous but not homozygous gene(s) linked tightly to H-2D region of k haplotype. Thus, the F1 resistance to GAIS is mediated by immune response of F1 recipients who miss the antigenic determinant(s) against that expressed on cell surface of GvHR inducing T lymphocytes. PMID- 2918226 TI - Phylogeny of regulatory proteins of the complement system. Isolation and characterization of a C4b/C3b inhibitor and a cofactor from sand bass plasma. AB - We have previously demonstrated that the alpha'-chain of human activated form of the fourth (C4b) and third (C3b) component of C are cleaved by plasma or serum from vertebrate species spanning through 300,000,000 yr of evolution yielding fragments identical with those obtained with human plasma. In this study, we investigated the molecular basis of this reaction. We chose barred sand bass plasma because this is the most primitive species analyzed possessing these activities. Barred sand bass plasma proteins were separated on a Sephadex G-200 column and the eluted samples analyzed for C4b and C3b cleavage. Individual fractions were inactive, but degradation was obtained when proteins of 380 and 155 kDa were combined. In contrast to the human regulatory proteins, the sand bass proteins require Ca2+ ions. K76COOH, an inhibitor of human factor I, inhibited the function of the 155-kDa but not of the 380 kDa-fraction. Thus it appears that the 155-kDa fraction functions as the C4b/C3b cleaving enzyme (I) and the 380-kDa material as its cofactor. Further purification of the 380-kDa fraction yielded a protein that by SDS-PAGE consisted of two noncovalently linked subunits of 110 and 42 kDa at a molecular ratio of 2:1. These two chains were antigenically distinct, and constitute domains of the same protein. The 110-kDa peptide binds C4b and not C3b but it fully expresses the cofactor function for the 155-kDa fraction on the cleavage of both C4b and C3b. Limited tryptic digestion of the 110-kDa domain demonstrated C4b binding activity in fragments of 34, 25, and 23 kDa. The activity of the 34-kDa fragment was the same as that of the undigested protein. Comparison of the amino acid composition of the barred sand bass cofactor and of human C4bp shows similar high content of cysteine and proline but not of tryptophan. It differs from human factor H in cysteine, serine, proline, and tryptophan. These studies indicate that regulatory proteins for the C4b and C3b C fragments may have appeared very early phylogenetically. PMID- 2918227 TI - A novel heteromorphic human cell surface alloantigen, gp60, defined by a human monoclonal antibody. AB - A human mAb (DSM1) generated from a patient immunized with irradiated allogeneic melanoma cells detects a new cell surface alloantigen of restricted cell type distribution. The Ag is a 60,000-Da glycoprotein (gp60) that displays considerable heteromorphism in its cytosolic and cytoskeletal (52 to 62 kDa) and membrane forms (60 to 64 kDa). The gp60 Ag has been purified using lectin affinity, ion exchange, and Mono P fast performance liquid chromatography. Rabbit antiserum against purified gp60 recognizes a homologous gp60 molecule on DSM1 nonreactive cells. Molecular properties of gp60 and a partial amino acid sequence of a tryptic gp60-derived peptide distinguish it from other known human alloantigens. This is the first report of a human alloantigenic system whose definition required a cell type other than those of bone marrow derivation. PMID- 2918228 TI - Trypanosoma musculi co-express several receptors binding rodent IgM, IgE, and IgG subclasses. AB - The present work demonstrates the expression of receptors for the Fc portion of rodent Ig by the murine parasite Trypanosoma musculi. By using a rosette assay adapted to the parasite morphology and by flow cytometry analysis, three distinct receptors were identified. A receptor binding rabbit or rat polyclonal IgG and mouse monoclonal IgG1, IgG2a, and IgG2b was found on parasites purified from the blood and the peritoneal cavity of infected mice and on parasites maintained in culture conditions. This IgG receptor was degraded by pepsin. A separate receptor, binding only mouse monoclonal IgG3 was observed on cultured parasites. A receptor binding rabbit, rat, and mouse IgM was found on cultured and peritoneal parasites, but not on blood parasites. This receptor did not bind IgG or IgA but it bound mouse and rat IgE as well as IgM. It was degraded by trypsin. IgG and IgM/IgE receptors were co-expressed on single parasites. They were not of host origin but synthesized by trypanosomes as shown by reexpression in vitro after proteolytic degradation. Their expression was variable with the development of trypanosomes both in vitro and in vivo. PMID- 2918229 TI - Disparate effects of in vitro low-dose UVB irradiation on intravenous immunization with purified epidermal cell subpopulations for the induction of contact hypersensitivity. AB - Low-dose ultraviolet (UV) B irradiation suppresses contact hypersensitivity (CH) reactions and alters the antigen-presenting function of epidermal cells (EC) in mice. To identify the EC sources of immunosuppression in this system, we examined the effect of UVB on the capacity of EC to induce and to regulate CH to trinitrochlorobenzene (TNCB). On day 0, cell sorter-purified populations of Ia+EC, Thy-1+EC, or Ia-/Thy-1-EC from CBA and C3H/HeJ mice were exposed to 200 J/m2 UVB from unfiltered FS20 Sunlamps, derivatized with hapten, and inoculated intravenously into syngeneic mice (5000 cells per inoculum). After 6 d, responsiveness was tested by challenging the left ear with 2% TNCB and measuring ear swelling responses. On day 14, regulation was tested by painting 7% TNCB on abdominal skin; after 6 d the right ear was challenged. Whereas mice which received haptenated unirradiated Ia+EC exhibited full CH responses without down regulation, mice inoculated with haptenated irradiated Ia+EC displayed significantly diminished primary responses and, on subsequent immunization, displayed down-regulation. On the other hand, panels of mice that received haptenated unirradiated Thy-1+EC, and haptenated irradiated Thy-1+EC both showed hyporesponsiveness as well as down-regulation. Intravenous immunization with haptenated unirradiated Ia-/Thy-1-EC or with haptenated irradiated Ia-/Thy-1-EC led in each instance to immunologically "null events." These findings indicate that UVB irradiation profoundly affected Ia+EC such that their capacity to sensitize for CH was not only abrogated, but that such treatment also resulted in down-regulation of CH responses. By contrast, the same phototreatment had no effect on the inherent property of Thy-1+EC to mediate down-regulation of CH. We conclude that Ia+EC are immunologically relevant targets of low-dose UVB radiation, and that two populations of irradiated EC, Ia+EC, and Thy-1+EC, have the potential to deliver down-regulatory signals in this model of immunosuppression. PMID- 2918230 TI - Removal of fibroblasts from human epithelial cell cultures with use of a complement fixing monoclonal antibody reactive with human fibroblasts and monocytes/macrophages. AB - A complement fixing IgM monoclonal antibody (1B10) that reacts with surface membrane molecules of human fibroblasts, tissue macrophages, and peripheral monocytes was produced. In Western blot analysis of detergent extracts of cultured human foreskin fibroblasts, antibody 1B10 detected protein bands of Mr 43,000 and 72-80,000. We used the 1B10 antibody with complement to eliminate most 1B10 positive nonepithelial cells from thymic epithelial (TE) cell cultures, thereby allowing us to grow highly enriched populations of human TE cells. PMID- 2918231 TI - Reappearance of CD1a antigenic sites after endocytosis on human Langerhans cells evidenced by immunogoldrelabeling. AB - We show evidence of the reappearance of CD1a antigenic sites on the surface of human isolated Langerhans cells after internalization of CD1a antigen/CD1a monoclonal antibody (BL6) complexes. The internalization was visualized by immunogoldlabeling, and the reappearance of CD1a binding sites was shown by immunogoldrelabeling. The relabeling was distinguished from the labeling either by using two sizes of gold granules (15 and 5 nm) or by quantitative estimation with one size of gold granules, before and after the relabeling. This reappearance of sites is cycloheximide insensitive, and is evidenced, even if the transfer of gold particles to lysosomes is blocked by the monensin. These results suggest that the reexpression of CD1a antigens is due to antigens stored in the cytoplasm or to recycling of internalized sites. Some immunolabeled Birbeck granules were observed in continuity with the plasma membrane, which demonstrates their membrane origin and their involvement in the endocytosis process. However, the weak labeling of these organelles makes us believe that they are not specialized CD1a endocytosis structures. PMID- 2918232 TI - Differential expression of the 4F2 activation antigen on human follicular epithelium in hair cycle. AB - The expression of the 4F2 activation molecule has been studied on keratinocytes of human skin and hair follicle using immunoperoxidase staining with three different anti-4F2 monoclonal antibodies. Membranes of basal layer keratinocytes of the skin uniformly expressed this antigen, whereas a differential expression of this antigen was located in specific areas of the hair follicle. Follicles in the complete anagen phase displayed a strong 4F2 positive staining at the matrix and the outer root sheath cells. This positive staining gradually decreased along the proliferation zone, and became negative at the migration zone. Positivity was recovered in follicular cells at the duct of the sebaceous gland and was maintained in the upper outer root sheath where those cells fuse with the keratinocyte basal monolayer. Changes were also detected on different phases of the hair cycle. Follicles in the catagen-telogen phase expressed a very low number of positive cells in the matrix. Positive labeling progressively increased when the follicle was at the initial anagen stage, reaching a complete staining pattern in hair at the anagen phase. These results suggest that the expression of this activation antigen on hair keratinocytes may be related to the proliferation, active metabolism, and/or activation states of these cell types. PMID- 2918233 TI - Molecular models of the intercellular lipid lamellae in mammalian stratum corneum. AB - Intercellular lipid lamellae in the stratum corneum constitute the barrier to water diffusion and may also play a role in cohesion between corneocytes. The lamellae arise from stacks of lamellar disks that are extruded from the granular cells and then fuse edge-to-edge to form sheets. It has been proposed that each lamellar disk is formed from a flattened vesicle, and therefore consists of two lipid bilayers in close apposition. In the present study, electron microscopic examination of ruthenium-tetroxide-fixed stratum corneum from mouse, pig, and human skin revealed that the double bilayer pattern persists in the intercellular lamellae. In addition, distinctive patterning of the intercellular lamellae has led us to propose novel molecular arrangements of the intercellular lipids. These include interlamellar sharing of lipid chains to produce lipid monolayers between pairs of bilayers. The pattern reflects the provenance of the intercellular lamellae from lamellar granule disks and the nonrandom orientation of the lamellar lipids. PMID- 2918234 TI - Ectopic growth of mouse whiskers from implanted lengths of plucked vibrissa follicles. AB - A method for transplanting whole or partial whisker follicles from adult mice to a site beneath the kidney capsule of syngeneic mice is described. Follicles were removed from the upper lip and the growing whiskers plucked. The follicles were either left intact or divided into two parts by transection and implanted under the kidney capsule. The intact whole follicles remained viable and regenerated whiskers which were later shed. The lower one-half or one-third follicle implants reorganized their base and produced a short, curled whisker. On the other hand, none of the upper one-half or two-thirds implants regenerated a dermal papilla, and no whisker production was observed. However, when a single dermal papilla which had been dissected out from another follicle was introduced into each upper follicle cavity in contact with the cut edge, a bulbar region emerged, and subsequently, a long, thick, medullated whisker developed from the implants. This technique should be useful in studying the induction and regeneration of adult mouse whiskers. PMID- 2918235 TI - Mast cell changes in a case of rapidly progressive scleroderma-ultrastructural analysis. AB - A 63-year-old woman had rapidly progressive scleroderma and died 4 months after the clinical appearance of her illness. Extreme itching of the affected skin was prominent. Electron microscopic study of the clinically uninvolved skin showed mainly normal mast cells. Mast cells in clinically involved skin showed a wide morphologic spectrum including evidence of cellular activation. There was an increased amount of cytoplasm occupied by polysomes and mitochondria and less cytoplasm occupied by granules. Most granules were pale and swollen, suggesting active degranulation. In some cases it was difficult to distinguish a hyperactive mast cell with only a few granules remaining from a fibroblast which had acquired granules by transgranulation. This case illustrates the active participation of mast cells in acute scleroderma. PMID- 2918236 TI - Immunohistologic demonstration of platelet-derived growth factor (PDGF) and sis oncogene expression in scleroderma. AB - Although the pathogenesis and mechanisms responsible for excessive connective tissue deposition are not known, it has been thought that specific growth factors may have an effect on scar formation by increasing the fibroblast population and by affecting the amount and types of matrix synthesized. In this regard, we explored the appearance and localization of TGF alpha, TGF beta, PDGF, and sis onc expression in situ. Sections of skin biopsies from eight scleroderma patients were investigated using specific antibodies to TGF alpha, TGF beta, human PDGF, and sis-onc products for immunohistochemistry. Most significantly, deposition of PDGF was detected in the endothelial lining of small capillaries in association with certain mononuclear cells of the perivascular infiltrates. In particular, strong labeling was observed in the cytoplasm of macrophages. Smooth muscle also appeared to be specifically labeled. Similarly, sis-onc product localized in the same areas. No significant staining was observed with antibodies to TGF alpha. TGF beta was found rather diffusely throughout the dermal connective tissue and was only occasionally observed in capillaries of lesions. We conclude that the PDGF may play an important role in the pathogenesis of scleroderma. PMID- 2918237 TI - Kinetics of excision repair in human skin. PMID- 2918238 TI - Membrane structural alterations in murine stratum corneum: relationship to the localization of polar lipids and phospholipases. PMID- 2918239 TI - Effects of 13-cis-retinoic acid on the hamster meibomian gland. AB - Systemic administration of 13-cis-retinoic acid caused a reduction of acinar tissue in the hamster meibomian gland. Histologic examination of treated meibomian gland tissue revealed a thickening of gland ductal epithelium and a decrease in the numbers of mature lipid-laden acinar cells. Morphometric analysis showed a reduction of up to 75% in mean volume of meibomian acinar tissue from animals fed a high dose of 13-cis-retinoic acid. Clinical observations in these animals included alopecia and weight loss. Ocular complications included crusting of the eyelid margin and the external surface of the lid and erythema of the conjunctiva. The model supports previous observations by the authors that systemic 13-cis-retinoic acid affects meibomian gland structure in a laboratory animal. The ocular side effects described in this model suggest that future functional studies may yield important insights into the complex relationship between meibomian gland morphology and function, and events on the ocular surface. PMID- 2918240 TI - Lipogenesis by isolated human apocrine sweat glands: testosterone has no effect during long-term organ maintenance. AB - Lipid synthesis by freshly isolated human apocrine glands has been measured by the incorporation of [U-14C] acetate. Incorporation is linear over 6 h at 1010 +/ 282 pmol/mg wet weight/h (n = 11; mean +/- sem). The lipid classes, as percentages of the total lipid synthesized, were found by TLC to be cholesterol 12.3 +/- 2.0, mono-glycerides 7.5 +/- 1.5, 1,2 di-glycerides 3.0 +/- 0.9, 1,3 di glycerides 3.5 +/- 0.5, tri-glycerides 28.4 +/- 1.8, free fatty acids 2.0 +/- 0.4, lysolecithin 15.4 +/- 3.9, sphingomyelin 9.9 +/- 4.3, phosphatidyl-choline 8.4 +/- 0.4, phosphatidyl-ethanolamine -inositol and -serine 1.8 +/- 0.1, phosphatidic acid and cardiolipin 3.3 +/- 0.5, and unidentified 3.3 +/- 0.5 (mean +/- sem, n = 5). Glands were maintained on permeable supports. After 10 d maintenance, electron microscopy showed that the cellular architecture had been preserved, that the ATP contents were the same as in freshly isolated glands, and that [U-14C] acetate incorporation was not significantly altered at 851 +/- 237 pmol/mg/h (n = 18). The addition of 3 microM testosterone had no effect on acetate incorporation at 844 +/- 231 pmol/mg/h (n = 18). The lipid classes and their proportions were similar to the values for fresh glands after 10 d maintenance both with and without testosterone. PMID- 2918241 TI - Changes in the relative amounts of endogenous and exogenous fatty acids in sebaceous lipids during early adolescence. AB - Skin surface lipid samples were collected from the scalps of 40 males, aged 9-15, and the lipid class composition of each was analyzed by quantitative thin layer chromatography. The ratio of wax esters/[cholesterol + cholesterol esters] (WE/[CH + CE]) increased with age. The wax ester, cholesterol ester, triglyceride, and free fatty acid classes were isolated from each sample and the fatty acid compositions were determined by capillary gas chromatography of fatty acid methyl esters (FAME) prepared from each lipid class. The concentrations of most of the different types of fatty acids were found to be correlated with the WE/[CH + CE] ratio. Those straight chain fatty acids that are thought to be synthesized mainly within the sebaceous glands, such as 14:0, 14:1, 16:1, and 18:2 delta 5, 8 tended to increase with increasing WE/[CH + CE], while fatty acids which circulate in the blood, such as 18:0, 18:1, and 18:2 delta 9, 12, tended to decrease with increasing WE/[CH + CE]. For the majority of straight chain fatty acid types, the data could be fitted to the equation y = a + b/[x + 1], which can be derived from simple assumptions concerning the origins of the various sebum components. The FAME from the wax esters were separated into saturated and monounsaturated fractions and analyzed by capillary gas chromatography to determine the concentrations of the different types of branched chain FAME present. In the wax esters, straight chain fatty acids tended to increase with increasing WE/[CH + CE], while terminally branched (iso and anteiso) fatty acids tended to decrease. Other branched chain fatty acids increased up to a WE/[CH + CE] ratio of about 2 and then decreased at higher ratios. PMID- 2918242 TI - A novel histone-stimulated protein kinase in normal and psoriatic epidermis. AB - During the course of studies on protein kinases in psoriatic epidermis, a novel histone-activated protein kinase activity was identified. This activity (referred to as PK-II because it was the second peak of protein kinase activity eluted from a DEAE column) was partially purified from the supernatant of an epidermal homogenate by DEAE-cellulose column chromatography. Although histone was not a substrate for phosphorylation, in the presence of histone, endogenous proteins of Mr 105 and 95 kDa were phosphorylated. Activity was not affected by Ca2+/phospholipid, cAMP, cGMP, cAMP-dependent kinase inhibitor, spermine, spermidine, calmodulin, EGF, or phorbol ester. Phosphorylation was specific for serine and threonine residues. A major peak of PK-II activity eluted from sepharose 6B with an apparent Mr of 100 kDa, suggesting that histone may stimulate autophosphorylation. The properties of PK-II resemble those recently described for a class of polypeptide-dependent protein kinases isolated from placenta, Ehrlich ascites tumor cells, and bakers' yeast. PK-II was significantly higher in psoriatic involved epidermis (32.6 +/- 11.6 pmol/min/mg protein) compared to psoriatic uninvolved epidermis (5.7 +/- 0.6 pmol/min/mg; p = 0.03) and normal epidermis (9.5 +/- 2.2 pmol/min/mg; p = 0.05). The function of histone stimulated protein kinase in epidermal function and its role in the pathophysiology of psoriasis remain to be explored. PMID- 2918244 TI - Abstracts of the ESDR-JSID-SID tricontinental meeting. Washington, D.C., April 26 30, 1989. PMID- 2918243 TI - Rapid detection of cutaneous herpes simplex virus infection with the polymerase chain reaction. AB - A simple and specific method for detecting herpes simplex virus infection in routinely processed paraffin-embedded biopsy specimens is described. DNA is extracted from paraffin blocks, and subjected to DNA amplification with the polymerase chain reaction. After 40 rounds, an amplified band can be detected after agarose gel electrophoresis and ethidium bromide staining. This band is specific for herpes simplex virus, because tissues infected with related viruses do not give this amplified band. We have been able to detect viral DNA in small punch skin biopsies with this procedure, which can take as little as 6 h. PMID- 2918245 TI - Characterization of very low density lipoprotein from Watanabe heritable hyperlipidemic rabbits. AB - We investigated the properties of very low density lipoprotein (VLDL) from two types of Watanabe heritable hyperlipidemic (WHHL) rabbits: one with a high incidence of coronary atherosclerosis (type 1), and the other with a low incidence (type 2). When incubated with mouse peritoneal macrophages, VLDL from type 1 WHHL rabbit (type 1-VLDL) stimulated cholesteryl ester synthesis 10.5-fold more than VLDL from the type 2 WHHL rabbit (type 2-VLDL) did. Moreover, a similar difference was seen in the stimulation of cholesteryl ester synthesis in peritoneal macrophages isolated from the WHHL rabbits. The mass ratios of cholesterol to protein in type 1- and type 2-VLDL were 5.69 and 2.05, respectively. Agarose gel electrophoresis of type 1-VLDL showed beta mobility, and that of type 2-VLDL showed pre-beta mobility. No difference was seen between the sizes of VLDL particles of the two types. The amount of apolipoprotein E in type 1-VLDL was greater than that in type 2-VLDL. In conclusion, the difference between type 1 and type 2 WHHL rabbits is at least partly due to the presence in type 1 animals of VLDL particles rich in cholesteryl esters and apolipoprotein E, particles which are very similar to beta-VLDL in conformation. PMID- 2918246 TI - Simultaneous fractionation of four placental neutral glycosphingolipids with a continuous gradient. AB - We describe a method for isolating milligram quantities of the four neutral glycosphingolipids, glucocerebroside, lactosylceramide, traiosylceramide, and globoside, from human placental tissue. This procedure is carried out on a silicic acid column eluted with a continuous chloroform-methanol gradient (19:1 to 4:1); the four glycosphingolipids elute as separate fractions with no need for further separation. The method is simple, rapid, and yields sufficient material to use as analytical standards for several hundred runs. The lipids have been identified by NMR spectroscopy. Placental tissue is freely available in most centers and is an excellent untapped source for these compounds. Given that lactosylceramide is not commercially available and that triaosylceramide (ceramide trihexoside) cannot be obtained in a reliable state, this technique represents an effective solution to this dilemma. PMID- 2918247 TI - Combined in-beam electron impact-B/E-linked scan mass spectrometry of oxazoline derivatives for the structure determination of long-chain unsaturated fatty acids. AB - Long-chain unsaturated fatty acids (UFA) having up to six double bonds are derivatized to 2-substituted 4,4-dimethyloxazolines (DMOX) and then analyzed by combined in-beam electron impact (IBEI)-B/E-linked scan mass spectrometry. This technique provides highly characteristic mass spectra and may serve as an auxiliary means for direct structure determination of individual UFA in mixtures. PMID- 2918248 TI - 24,25-epoxysterols. Differentiation of 24R and 24S epimers by 13C nuclear magnetic resonance spectroscopy. AB - The 24R and 24S epimers of the acetates of 24,25-epoxycholesterol and 24,25 epoxylanosterol have been prepared and purified by preparative normal phase high performance liquid chromatography. Neither pair of epimers could be differentiated by 1H NMR. However, the 13C NMR spectra of the epimeric pairs were sufficiently different to permit samples of individual epimers to be assigned as 24R or 24S. PMID- 2918249 TI - Effect of cholesterol nucleation-promoting activity on cholesterol solubilization in model bile. AB - Human bile contains a factor with cholesterol nucleation-promoting activity that binds to concanavalin A-Sepharose. In this study we have investigated the effect of this activity on the dynamics of lipid solubilization in supersaturated model bile. A concanavalin A binding protein fraction of human bile was mixed with model bile and the effect on the distribution of cholesterol and phospholipid between mixed micelles and phospholipid/cholesterol vesicles was studied by means of density gradient ultracentrifugation. The nucleation-promoting activity containing fraction induced a transfer of cholesterol and phospholipid from the micellar to the vesicular phase. This led to a decrease in the density of the vesicular fraction. We have also studied the effect of promoting activity on the nucleation time of an isolated vesicle fraction. A decrease of the nucleation time of 10.7 +/- 1.3 to 2.3 +/- 0.3 days was observed. In conclusion, a concanavalin A binding protein fraction from human bile stimulated cholesterol nucleation via a double effect; it increased the amount of vesicular cholesterol and phospholipid, and it also directly induced nucleation of cholesterol from the vesicles. PMID- 2918250 TI - Effect of dietary supplementation with a fish oil concentrate on the alkenylacyl class of ethanolamine phospholipid in human platelets. AB - It has been demonstrated that the alkenylacyl class of ethanolamine phospholipid (PE) represents one of the major forms of eicosapentaenoic acid (EPA)-containing phospholipid in the circulating platelets isolated from human subjects consuming a fish oil concentrate. Since the alkenylacyl PE from human platelets is enriched in the eicosanoid precursor arachidonic acid (AA) and the n-6 polyunsaturate adrenic acid (AdA), it was of interest to study changes in alkenylacyl PE fatty acid composition upon fish oil supplementation. Healthy volunteers were given 20 capsules of MaxEPA daily (3.6 g of EPA plus 2.4 g of docosahexaenoic acid, DHA) for 6 weeks followed by a 6-week recovery period. Washed platelet suspensions were prepared and the fatty acid compositions of the phospholipid components were evaluated by thin-layer and gas-liquid chromatography at weeks 0, 3, 6, 9, and 12. Fatty acid composition changes were more pronounced in the alkenylacyl PE than in other platelet phospholipids as a result of fish oil consumption. The alkenylacyl PE exhibited a greater drop (by 20.3 mol%, i.e., from 72.0 to 51.7 mol%) in AA than diacyl PE (by 1.6 mol%) or total (predominantly diacyl) choline phospholipids (PC) (by 4.5 mol%). In alkenylacyl PE, the predominant reservoir of AdA in human platelet phospholipid, a dramatic reduction in the level of AdA also resulted with MaxEPA supplementation (from 7.9 to 3.1 mol%); diacyl PE and total PC decreased by 0.6 and 0.3 mol%, respectively. With respect to the n-3 fatty acids, EPA rose by 12.5 mol% in alkenylacyl PE, compared to only 3.8 and 2.5 mol% in diacyl PE and total PC, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918251 TI - High density lipoprotein stimulates sterol translocation between intracellular and plasma membrane pools in human monocyte-derived macrophages. AB - Binding of high density lipoprotein (HDL) to its receptor on cultured fibroblasts and aortic endothelial cells was previously shown to facilitate sterol efflux by initiation of translocation of intracellular sterol to the plasma membrane. After cholesterol-loaded human monocyte-derived macrophages were incubated with either [3H]mevalonolactone or lipoprotein-associated [3H]cholesteryl ester to radiolabel intracellular pools of sterol, incubation with HDL3 led to stimulation of 3H labeled sterol translocation from intracellular sites to the cell surface which preceeded maximum 3H-labeled sterol efflux. A similar pattern was demonstrated for macrophages that were preloaded with cholesterol derived from either low density lipoprotein (LDL), acetyl-LDL, or phospholipase C-modified LDL. However, in macrophages that were not loaded with cholesterol, HDL3 stimulated net movement of 3H-labeled sterol from the plasma membrane into intracellular compartments, the opposite direction from that seen for cholesterol-loaded cells. A similar influx pattern was found in nonloaded macrophages and fibroblasts that were labeled with trace amounts of exogenous [3H]cholesterol. Cholesterol translocation from intracellular pools to the cell surface of cholesterol-loaded macrophages appeared to be stimulated by receptor binding of HDL, since chemical modification of HDL with tetranitromethane (TNM), which abolishes its receptor binding, reduced its ability to stimulate 3H-labeled sterol translocation and efflux. In nonloaded cells, however, the ability of HDL3 to stimulate sterol efflux and movement of sterol from the plasma membrane into intracellular pools was unaffected by TNM modification. Thus, binding of HDL to its receptor on cholesterol-loaded macrophages appears to promote translocation of intracellular cholesterol to the plasma membrane followed by cholesterol efflux into the medium. However, in nonloaded macrophages, HDL stimulates sterol movement from the plasma membrane into intracellular pools by a receptor-independent process. PMID- 2918252 TI - Effect of a fish oil diet on the composition of rat neutrophil lipids and the molecular species of choline and ethanolamine glycerophospholipids. AB - When rats were fed a corn oil versus a corn oil-fish oil diet the overall phospholipid content and composition as well as the subclass distribution of the choline- and ethanolamine-containing glycerophospholipids from neutrophils were not altered. The serine-containing glycerophospholipids were characterized by high levels of stearic and oleic acids. When fish oil was added to the diet it replaced some of the arachidonate in both the inositol- and the serine-containing glycerophospholipids. In the corn oil-fed animals, 25.2 and 33.6 mole %, respectively, of the molecular species of 1,2-diacyl- and 1-O-alkyl-2-acyl-sn glycero-3-phosphocholine contained arachidonate. The values for 1,2-diacyl and 1 O-alk-1'-enyl-2-acyl-sn-glycero-3-phosphoethanolamine were, respectively, 41 and 55.8 mole %. When half of the 5% corn oil in the diet was replaced by fish oil, there was a 53, 38, 27, and 25% reduction, respectively, in the level of arachidonate in these four lipid subclasses. The amount of 5,8,11,14,17 eicosapentaenoic acid incorporated into these four subclasses was always less than the decline in arachidonic acid. This was due, in part, to the acylation of small amounts of 22-carbon (n-3) acids into these lipids. Molecular species analysis demonstrated that 5,8,11,14,17-eicosapentaenoic acid paired with the same components at the sn-1 position, and in the same ratio, as did arachidonic acid. The amounts of 16- and 18-carbon saturated and unsaturated fatty acid at the sn-2 position were not altered by dietary change. Collectively, these findings suggest that 5,8,11,14,17-eicosapentaenoic and arachidonic acids are metabolized in a similar way by neutrophils. These studies also support the concept that neutrophils contain two metabolic pools of phospholipids. One pool is altered by dietary fat change while the pool containing 16- and 18-carbon acids is resistant to change when fish oil is included in the diet. PMID- 2918253 TI - Lipid content and lipid type as determinants of the epidermal permeability barrier. AB - During terminal differentiation, mammalian epidermal lipids undergo striking changes in both composition and distribution. Phospholipids and neutral lipids are replaced by a mixture of ceramides and neutral lipids organized in intercellular lamellar bilayers. Whether all of these lipids and/or whether specific lipid classes regulate permeability barrier function is not known. When hairless mice were treated with acetone, the degree of barrier perturbation (measured as transepidermal water loss, TEWL) increased linearly with the amount of lipid removed. Moreover, virtually all lipid species appeared to be removed by acetone treatment. In contrast, the nonpolar organic solvent, petroleum ether, while removing greater amounts of lipids, provoked lesser barrier abnormalities. As determined by both quantitative thin-layer chromatography and histochemistry, petroleum ether selectively extracted nonpolar lipids leaving sphingolipids and free sterols in place. In petroleum ether-treated animals, subsequent acetone treatment removed additional sphingolipids and produced a dramatic increase in TEWL. A linear relationship existed for the quantities of sphingolipid removed and degree of barrier disruption in acetone-treated, but not petroleum ether treated animals. These results support a relationship between the total lipid content of the stratum corneum and barrier function. Secondly, although the results demonstrate the participation of the total lipid mixture in the barrier, removal of nonpolar species alone appears to cause only a modest level of barrier disruption, while removal of sphingolipids and free sterols leads to a more profound level of barrier perturbation. PMID- 2918254 TI - Studies on the catalytic site of rat liver HMG-CoA reductase: interaction with CoA-thioesters and inactivation by iodoacetamide. AB - The localization of reactive cysteines and characterization of the HMG-CoA binding domain of rat liver HMG-CoA reductase were studied using iodoacetamide (IAAD) and short-chain acyl-CoA thioesters. Freeze-thaw-solubilized HMG-CoA reductase is irreversibly inactivated by IAAD with a second order rate constant of 0.78 M-1 sec-1 at 37 degrees C and pH 7.2. This IAAD inactivation is slowed down by pretreatment of the enzyme with disulfides, indicating that inactivation of HMG-CoA reductase occurs mainly through alkylation of specific cysteine residues in the protein. The substrate HMG-CoA, but not NADP(H), effectively protects the reductase from IAAD inactivation. When both HMG-CoA and NADP(H) are present, the reductase is inactivated by IAAD at a rate much faster than the inactivation in the presence of HMG-CoA alone. Of the two moieties of the HMG-CoA thioester, the CoA moiety confers protection from IAAD inactivation whereas HMG is totally ineffective. A series of CoA-thioesters of mono- and dicarboxylic acids of various size were tested for their effect on the activity of HMG-CoA reductase. The CoA analog, desulfo-CoA (des-CoA), and all CoA-thioesters of monocarboxylic acids of up to 6 carbons in length exhibit mixed-type inhibition of reductase activity. The competitive inhibition constants (Ki) for these compounds vary between 1 and 2 mM, whereas the noncompetitive component (K'i) is relatively constant (540 +/- 20 microM). As the acyl chain length increases beyond 6 carbons, the thioesters of monocarboxylic acids become more potent and acquire the characteristics of pure noncompetitive inhibitors. In contrast, the monothioesters of dicarboxylic acids are pure competitive inhibitors with Ki values which are similar to the Ki values of the corresponding thioesters of monocarboxylates. HMG does not affect reductase activity in concentrations of up to 2 mM, yet it greatly enhances the inhibition of the enzyme by des-CoA. Specifically, HMG affects only the Ki value of des-CoA by decreasing it from 1030 microM to 280 microM. The results indicate that reactive cysteine(s) are localized in the catalytic site of HMG-CoA reductase. Within the active site, these cysteines are closely associated with and probably participate in the binding of the CoA moiety of the substrate HMG-CoA. The results are also consistent with the existence of a noncatalytic hydrophobic site in HMG-CoA reductase. PMID- 2918255 TI - Application of criminal antitrust sanctions to health care professionals. PMID- 2918256 TI - Advances in the treatment of non-Hodgkin's lymphoma. AB - The use of more aggressive multiagent combination chemotherapy for the treatment of advanced diffuse aggressive lymphomas has resulted in a dramatic change in the overall outlook in patients with this disease. Once rarely curable or even controllable, it is now one of the most curable of disseminated malignancies. Sustained, disease-free survival rates have risen from 5% in the 1960s to approximately 65% in the 1980s. The 35% who do not achieve initial CR generally experience a fulminant course, with patients rarely surviving more than 2 years. Subsequent clinical trials will explore a number of new approaches including short-course, dose-intense induction regimens, addition of new agents into combinations (including cisplatin, vindesine, M-AMSA, ifosfamide, and methyl GAG), and the use of biologicals (monoclonal antibodies, interleukin-2 plus LAK cells, and tumor necrosis factor). Salvage therapy for those who experience recurrence of disease can produce responses in 45 to 65% of patients, but remission duration is short, and median survival time is usually less than 1 year. Recent interest in high-dose chemotherapy with or without total body irradiation, followed by autologous bone marrow transplantation for relapsed patients, has produced some encouraging results. PMID- 2918258 TI - Diverse systems, common ground: impressions of the World Medical Assembly. PMID- 2918257 TI - Surgical management of the morbidly obese: some personal comments. PMID- 2918259 TI - Medical experience and preparedness for handling radiation injuries. AB - Medically significant overexposures have not occurred in 30 years of operating commercial nuclear power plants in this country. However, the medical communities around reactors in Georgia as well as the rest of the country, maintain a vigilance and preparations to handle these cases through semi-annual exercises using simulated patients. The programs at the Hatch and Vogtle plants provide not only for local care but also for specialty medical teams to arrive and assist in the triage and evacuation of casualties to definitive care centers for complete evaluation and treatment. This is not unlike the plan the Soviets used so successfully at Chernobyl. PMID- 2918260 TI - Melatonin analogues induce pigment granule condensation in isolated Xenopus laevis melanophores in tissue culture. AB - 2-Iodomelatonin, a ligand which has recently been used to identify melatonin binding sites in the brain, produced condensation of pigment granules when added to isolated Xenopus laevis melanophores in culture. Melatonin (EC50 = 5.7 x 10( 13) mol/l), 2-iodomelatonin (EC50 = 3.4 x 10(-12) mol/l) and also 2 chloromelatonin (EC50 = 2.9 x 10(-13) mol/l) were all potent agonists in this test. Melatonin analogues in which the side-chain was conformationally restricted by linkage to the 2-position of the indole ring were inactive (EC50 greater than 10(-6) mol/l). The remarkable sensitivity and selectivity of this pigment condensation response suggests it will be useful in future studies of melatonin agonists and antagonists. PMID- 2918261 TI - The route of secretion of inhibin from the rat testis. AB - Levels of immunoactive and bioactive inhibin were measured in venous blood collected at a point just before (testicular venous) and after (spermatic venous) its passage through the mediastinal venous plexus over the anterior pole of the rete testis, and compared with levels in peripheral venous blood and testicular interstitial fluid (IF). In 15 control rats, levels of inhibin were highest in IF (8900 +/- 432 ng/l; mean +/- SEM) and lowest in peripheral (290 +/- 32 ng/l) and testicular (288 +/- 34 ng/l) venous blood, whilst levels in spermatic venous blood (633 +/- 99 ng/l) were always higher (P less than 0.002) than the levels in testicular venous blood. The latter difference was either reduced or abolished after disruption of spermatogenesis by local heating of the testes 8, 14, or 21 days previously, and by ligation of the efferent ducts for 6 h or more, but was not affected by acute removal of the epididymis. It is concluded that inhibin secreted into seminiferous tubule fluid may be reabsorbed from the rete testis and this may be the major route by which it reaches the peripheral bloodstream in rats with normal spermatogenesis. PMID- 2918262 TI - Growth hormone regulates the level of insulin-like growth factor-I mRNA in rat skeletal muscle. AB - Levels of mRNA for the insulin-like growth factor-I (IGF-I) in rat heart and skeletal muscle and its dependence on GH were investigated using a solution hybridization assay. Levels of IGF-I mRNA decreased following hypophysectomy, and replacement therapy with human GH (hGH) normalized heart and skeletal muscle levels. The stimulatory effect of hGH was dose-dependent, the lowest effective dose being 100 micrograms. A significant increase of IGF-I mRNA was observed 60 min after s.c. administration of 100 micrograms hGH and the maximum increase was apparent 6-12 h after hGH injection. Administration of 200 micrograms IGF-I or 11 micrograms insulin did not significantly change levels of IGF-I mRNA. The results show that GH regulates the level of IGF-I mRNA in rat heart and skeletal muscle and give further support to the hypothesis that locally produced IGF-I might be a local mediator for the direct stimulatory effect of GH on the growth and development of heart and skeletal muscle. PMID- 2918263 TI - The functional activity of hypothalamic 5-hydroxytryptamine neurones in broody bantam hens. AB - An assessment was made of the possible role of hypothalamic 5-hydroxytryptamine (5-HT) in the regulation of prolactin secretion in broody bantam hens. Prolactin secretion was stimulated less in incubating hens deprived of their nests for 24 h (nest-deprived) than in laying hens after administration of the 5-HT receptor agonist quipazine, or precursor 5-hydroxytryptophan. One type of 5-HT-binding site was found in the anterior and posterior hypothalami of out-of-lay, incubating and laying hens. Differences in prolactin secretion in these birds could not be accounted for by changes in the abundance of this type of 5-HT binding site. Another type of 5-HT-binding site, with a higher density but lower affinity, was found in the anterior hypothalami of laying hens. No specific 5-HT binding sites were found in the anterior pituitary gland. The turnover rates of 5 HT were compared in the anterior and posterior hypothalami of laying, incubating and nest-deprived hens. The turnover rates were estimated from the rate of accumulation of 5-HT after inhibiting its catabolism using the monoamine oxidase inhibitor, pargyline, or by measuring the ratio of the concentrations of 5-HT and its major metabolite, 5-hydroxyindole acetic acid. Both methods of measurement gave the same results. The turnover of 5-HT was increased in the anterior but not posterior hypothalami of incubating hens when compared with laying or nest deprived hens. There was also a significant increase in turnover of 5-HT in the posterior hypothalami in nest-deprived hens when compared with laying or incubating birds.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918264 TI - Stress alters immune function and disease resistance in chinook salmon (Oncorhynchus tshawytscha). AB - We examined the effects of acute stress on the immune system and disease resistance of juvenile chinook salmon (Oncorhynchus tshawytscha) in laboratory and clinical trials. Immune function, as measured by the ability of lymphocytes from the anterior kidney to generate specific antibody-producing cells (APC) in vitro, was depressed 4 h after stress, when plasma cortisol levels were highest. At the same time, resistance to the fish pathogen, Vibrio anguillarum, was also depressed. Compared with controls, plasma cortisol and APC of stressed fish were unchanged after 24 h, and disease resistance was enhanced as evidenced by higher survival rate and longer mean time to death of mortalities. After 7 days, even though numbers of APC were depressed, plasma cortisol concentration and disease resistance did not differ from controls. This pattern was generally the same, independent of the type of stress applied: i.e. being held out of water in a dipnet for 30 s, manipulation during hatchery operations for 4 h, or transportation for 9 h. These and earlier findings suggest that similar endocrine immune interactions operate in the mammalian and salmonid systems during acute stress. PMID- 2918265 TI - Oestradiol, vasoactive intestinal peptide and fibroblast growth factor in the growth of human pituitary tumour cells in vitro. AB - The growth of two human prolactin-secreting cell lines developed in our laboratory has been investigated in response to a number of factors. Oestrogen stimulated the synthesis of DNA and protein and increased prolactin secretion. Dexamethasone had the opposite effect to oestrogen. In the presence of serum, epidermal growth factor (EGF) inhibited cell growth at concentrations of 5 ng/ml. Known secretagogues of prolactin (vasoactive intestinal peptide (VIP), TRH, bombesin and neurotensin) were investigated for their action on cell growth but only VIP had a stimulatory effect. Two preparations of fibroblast growth factor (FGF) were studied. One form, derived from bovine pituitary glands, stimulated human pituitary cell growth. In contrast, another FGF, of the basic type (rFGF), was inhibitory to cell growth, increasing the time for cell doubling from 30 to 72 h. This inhibitory effect of rFGF was modified but not abolished by serum, oestradiol, platelet-derived growth factor or EGF. We conclude that bovine pituitary contains at least two fibroblast growth factors, both of which stimulate fibroblast cell growth, but one stimulates and the other inhibits human pituitary tumour cell growth. PMID- 2918266 TI - Feedback regulation by progesterone of stress-induced prolactin release in rats. AB - We have previously found that modifications to serum progesterone concentration have profound inhibitory effects on prolactin release in response to ether stress. The objective of the present study was to determine the effect of ether stress on progesterone secretion and the role of this steroid in ether-induced prolactin release. Serum progesterone concentration, 5 min after ether stress had been applied over a 2-min period, was consistently increased in male rats, in cyclic rats on the mornings of pro-oestrus and oestrus, and in androgenized rats in permanent oestrus. Ovariectomized androgenized rats showed the same response. Adrenalectomy of male and female rats abolished the progesterone increase induced by stress. Thus, the progesterone secreted by stressed rats is mostly of adrenal origin. In groups of male and pro-oestrous rats, circulating concentrations of prolactin and progesterone were measured from 5 to 60 min after stress. In both sexes the serum prolactin concentration was significantly increased at only 5 and 10 min after stress when compared with control values. In pro-oestrous rats the serum progesterone concentration was significantly higher than in controls at 5, 10 and 20 min after stress, whilst in male rats the concentration remained significantly higher at 30 min. Thirty minutes after the first stress, male and proestrous rats were etherized for 2 min, and bled 5 min after removal from the ether container. In female rats this second stress produced only a slight but significant increase in serum prolactin concentrations, whereas in male rats prolactin concentrations did not increase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918267 TI - Endometrial responses to a deciduogenic stimulus in ovariectomized rhesus monkeys treated with oestrogen and progesterone. AB - To establish an artificial model for the study of decidual cell reaction in the rhesus monkey, long-term ovariectomized animals were treated with oestrogen followed by progesterone and an artificial deciduogenic stimulus was applied on day 16 of the treatment cycle. Histological examinations of the endometrial samples on different days following stimulation showed prominent epithelial plaque reaction by day 20. Marked subepithelial oedema surrounding plaque cells was also noted. On day 32, degenerating plaque cells with leucocytic infiltration were found. Beginning on day 24 of hormone treatment, stromal fibroblasts adjacent to plaque and glands showed swelling with rounding-up and enlargement of nuclei; these stromal cells appeared more decidual-like with moderate amounts of hypertrophy and few were binucleate by day 28. Endometrial granular cells became more conspicuous and appeared to increase in numbers adjacent to glands and blood vessels. Endometrial glands showed no notable changes, and were mostly tortuous with columnar epithelium and apocrine-type secretions. Around days 40 and 48 of the treatment cycle, the luminal margins of the glands became bosselated, and significant amounts of secretion were present in the glandular lumen. Measurement of immunoreactive concentrations of oestradiol-17 beta and progesterone in endometria from traumatized, hormone-treated monkeys revealed significant (P less than 0.01) decreases in levels of oestradiol with time while the level of progesterone remained unchanged (P greater than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918268 TI - Androgen regulation of major mRNAs for proteins of the immature and adult mouse vas deferens. AB - When total RNA and poly (A)+ RNA extracted from the adult mouse vas deferens were translated in the rabbit reticulocyte lysate protein synthesizing system, they showed a similar electrophoretic pattern of about 20 protein bands of widely varying molecular weights. Within the total mRNA population, three functional mRNAs coding for proteins with molecular weights of 24, 34.5 and 36 kDa showed marked changes after 1 month of castration. The time-course of the response of the translatable proteins showed that while 3 days after castration the 24 and 36 kDa bands were missing, the mRNA coding for the 34.5 kDa band was markedly reduced only 20 days after castration. The negative effect of castration on the three mRNAs could be completely reversed by treatment with testosterone. When total RNA extracted from the immature mouse vas deferens was translated, the 24, 34.5 and 36 kDa protein bands were detectable in 10-day-old males and were synthesized in significant amounts between 10 and 20 days (24 and 36 kDa bands) or between 20 and 30 days (34.5 kDa band). Based on its electrophoretic and immunological properties, the 34.5 kDa protein band, which is predominant in the translation products, was identified as the major androgen-dependent protein previously described in vivo. PMID- 2918269 TI - Oestrogen receptors and effects of oestradiol administration on mRNA synthesis in the limbic system of the neonatal female rat. AB - There is sexual dimorphism of specific species of mRNA in the neonatal rat brain and this sexual dimorphism may be imprinted by steroids of testicular origin during the perinatal period. According to current theories, only aromatizable androgens may cause sexual differentiation of sexual behaviour and function in the adult. The effects of oestradiol benzoate on mRNA synthesis in the neonatal female limbic system were therefore studied. In addition, cytosolic and nuclear oestrogen receptors were measured after administration of testosterone propionate, oestradiol benzoate or dihydrotestosterone (DHT). An attempt was made to distinguish between the brain oestrogen receptor and the plasma oestrogen binding protein, alphafoetoprotein (AFP) by isoelectric focussing. After injection of 50 micrograms oestradiol benzoate s.c. to neonatal female rats, the expression of mRNA coding for sexually dimorphic proteins appeared to be changed to a male-type pattern. The overall density of labelling was noticeably greater and specific changes in labelled proteins were observed. These effects were observed within 3 h of injection. Both testosterone and oestradiol caused a marked depletion of cytosolic oestrogen receptors in the limbic system whereas DHT was ineffective in this respect. Nuclear receptors were present in equal abundance in male- and female-derived nuclei and only oestradiol was able to cause a significant (P less than 0.025) increase in nuclear oestrogen receptors. The receptor and AFP could be distinguished by isoelectric focussing, since the pI of the receptor was 7.05, while that of AFP was 4.5. These results are consistent with the possibility that oestradiol alters transcription in the neonatal rat brain and may do this through the oestrogen receptor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918270 TI - Lipid lowering in severe familial hypercholesterolaemia: efficacy and safety of a new regenerating system for selective apheresis of apolipoprotein B-containing lipoproteins. AB - Preliminary experience of the efficacy and safety of a new regenerating system for selective extracorporeal removal of apolipoprotein B-containing lipoproteins is described. Four patients with familial hyperlipoproteinaemia were studied on 10 occasions. A system of two, parallel, dextran sulphate cellulose columns was used, and plasma was processed continuously by passage through one of the columns while the other was being regenerated. With this procedure, reductions of very low density and low density lipoprotein cholesterol levels by 73 and 43%, respectively, could be achieved after treatment for 2.5-3 h (1000-3200 ml of plasma volume). No clinically relevant changes in the concentrations of other plasma proteins, including high density lipoproteins, were observed, and the treatment was well tolerated. We conclude that continuous selective apolipoprotein B apheresis is a safe and efficient lipid-lowering procedure which may be used both for metabolic investigations and for studies on possible regression of atherosclerosis. PMID- 2918271 TI - Platelet-derived growth factor: structural and functional aspects. PMID- 2918272 TI - Experiences of clodronate treatment of multifocal eosinophilic granuloma of bone. AB - Clodronate, an inhibitor of osteoclast function, reduces bone resorption in osteolytic metastases and in multiple myeloma. We have evaluated its ability to decrease bone destruction in patients with multifocal eosinophilic granuloma of the skeleton. Two patients, whose multifocal bone granulomas appeared with a frequency of about 6 months, received 1.6 g day-1 oral clodronate for 6 months. Both patients had a reduction in serum calcium level which was accompanied by a decline in the fasting urinary hydroxyproline/creatinine and calcium/creatinine ratios and a slight increase in parathyroid hormone (PTH) level. Pain relief was observed in both patients. No new bone lesions were seen during the treatment and the old lesions healed. After discontinuing the therapy, however, new painful lesions appeared after 5 years in patient 1 and after 3, 4 and 5 years in patient 2. We suppose that clodronate delayed the appearance of new granulomas. PMID- 2918274 TI - Newborn's discrimination among mid- and long-wavelength stimuli. AB - Recent anatomical and behavioral evidence suggests that important visual functions like color vision may be severely limited at birth. Therefore, we examined human newborns' ability to discriminate among stimuli of different wavelength by habituating them to a 16 degrees chromatic square of widely varying luminance (as wide as 1.1 log cd/m2) and then testing for recovery of habituation to a different chromatic square of the same size. In the first experiment, newborns showed evidence of recovery to a 650-nm (peak wavelength) red square after habituating to 545-nm green squares, but they did not recover to the red or the green after habituating to 585-nm yellow squares. In a second experiment using the same procedure, newborns did not show evidence of discriminating the 650-nm red from the 545-nm green when the stimulus size was reduced to 8 degrees. These data suggest that human newborns are capable of making a chromatic discrimination within the spectral region above 540 nm (the Rayleigh region) but their ability is limited to chromatic stimuli of very wide spectral separation and of very large size. Possible neurological bases underlying this immaturity are discussed. PMID- 2918273 TI - Early understanding of perception as a source of knowledge. AB - Two studies investigated preschool children's ability to infer another person's knowledge or ignorance on the basis of that person's recent perceptual experience. In Experiment 1 children were questioned about their own and a puppet's knowledge of a hidden object's color and about their own and the puppet's ability to see the hidden object. Three- and 4-year-olds attributed knowledge and perceptual experience to the person (either themselves or the puppet) who had viewed the hidden object, but not to the person who did not view it. Experiment 2 further investigated 3-year-olds understanding of perception as a source of knowledge. Children were asked to indicate which of two puppets, one who had viewed a hidden object and one who had not, would be able to tell them the object's color. Children chose the correct puppet more often than would be predicted by chance. The results of these experiments suggest that understanding of perception as a source of knowledge is present by the age of 3 years. PMID- 2918275 TI - The development of children's achievement-related expectancies and subjective uncertainty. AB - Children between the ages of 3 and 6 years were asked to predict their success or failure in two different tasks: a box-lifting task and a task in which marbles had to be rolled through gates of different widths. Both tasks had five difficulty levels which were presented either simultaneously or successively. Along with the verbal or nonverbal responses to questions about their chances of success, the time children needed to make the prediction (decision time), the number of eye movement during the decision time, and, in the box-lifting task, the time taken to approach the box were assessed. The results indicated that children from 3 years on make realistic assessments of their chances for success at the five different difficulty levels. The simultaneous presentation mode enables the children to make more realistic success predictions only in the marble-rolling task. For the box-lifting task, children seem to have a stabilized difficulty scale which allows sure predictions without the whole range of difficulty levels being physically presented. PMID- 2918276 TI - Tactual learning and cross-modal transfer of an oddity problem in young children. AB - The ability to solve tactual oddity problems, and transfer of oddity learning across the visual and the tactual modalities, was studied in 3- to 8-year-old children (N = 294). Oddity tasks consisting of one odd and two equal objects were made from stimuli that were easily discriminated visually and tactually. The results showed that tactual oddity learning increased gradually with age. The growth in tactual performance begins later than visual, suggesting that children are more adept at encoding visual stimulus invariances or relational properties than tactual ones. Bidirectional cross-modal transfer of oddity learning was found, supporting the suggestion that such transfer occurs when training and transfer oddity tasks share a common vehicle dimension. The cross-modal effect also shows that oddity learning is independent of a specific modality-labeled perceptual context. Our results are consistent with the view that development of oddity learning depends on a single rather than a dual process, and that the oddity relation may be treated as an amodal stimulus feature. PMID- 2918277 TI - Validity testing of commercial urine cocaine metabolite assays: I. Assay detection times, individual excretion patterns, and kinetics after cocaine administration to humans. AB - A validity study of eight commercial urine assays for detection of cocaine metabolite was performed on clinical specimens collected from human subjects who received single 20-mg intravenous doses of cocaine hydrochloride. The specimens were collected under controlled conditions and analyzed in random order under blind conditions. Benzoylecgonine concentration in each specimen also was determined by gas chromatography/mass spectrometry (GC/MS). Mean times of detection of the last positive specimen (greater than or equal to 300 ng/mL of benzoylecgonine equivalents) after cocaine administration varied among seven of the commercial tests from 16.9 to 52.9 h in the following ascending order: Toxi Lab less than TDx = EMIT dau = EMIT st less than Abuscreen less than Coat-A-Count = Double Antibody. In contrast, a commercial spot test (KDI Quik Test) which was evaluated for detection of cocaine metabolite produced both false positives and false negatives for benzoylecgonine and was not considered to be a valid test for detection of cocaine metabolite. Half-lives of excretion of benzoylecgonine among four subjects varied from 5.9 to 7.9 h, and overall recovery of benzoylecgonine varied from 15.0 to 34.3% of the administered dose of cocaine. PMID- 2918278 TI - Temporal clustering of heroin overdoses in Washington, DC. AB - During the 5-day period from 28 Feb. 1985 through 4 March 1985, 24 heroin overdoses occurred in the District of Columbia. Statistical tests for clustering of fatal and nonfatal overdoses during this interval identified 7 heroin-related deaths that occurred on March 1 to 2 as a statistically significant cluster (p = 0.007). An extension of the analysis for clustering to a 15-month period identified 2 additional clusters, 1 of fatal overdoses and 1 of nonfatal ones. When all victims of fatal overdose in cluster intervals were combined and compared with all other heroin-related deaths, no significant differences were noted for levels of morphine or ethanol in blood. However, bile morphine concentrations of cluster decedents were significantly lower than those of noncluster decedents (p = 0.033), suggesting that these decedents were less tolerant to the effects of narcotics than the comparison group. Heroin concentrations in street-level heroin samples collected during clusters did not differ from those collected during comparison intervals. These data conflict with the traditional explanation of overdose clusters, which attributes these events to unusually potent street-level heroin. PMID- 2918280 TI - Estimation of postmortem interval using kinetic analysis of the third component of complement (C3) cleavage. AB - To estimate postmortem interval (PMI), spontaneous cleavage of the third component of complement (C3) was studied in aged blood and cadaveric blood by crossed immunoelectrophoresis. Using the kinetics of C3 cleavage in vitro described as dC/dt = -kC, where C is the concentration of native C3 at time t and k is a first-order rate constant, Arrhenius' equation, and another equation which assumes a linear drop of body temperature after death, the percentages of C3 cleavage were calculated. There was a significant positive correlation between the calculated percentages and the measured percentages of up to 10% in cadaveric blood. We found that the comparison between the calculated percentage of C3 cleavage for each optional postmortem interval and the measured percentage of up to 10% in cadaveric blood leads to the estimation of PMI. This approach is one step towards the development of an accurate method for determining PMI based on C3 cleavage, that is, on a first-order reaction. PMID- 2918279 TI - Comparison of chemical methods for determining postmortem interval. AB - Accurate determination of postmortem interval (PMI) is a problem for the forensic thanatologist, especially in unwitnessed deaths. A number of objective chemical methods for determining PMI have been developed, the most widely used being accumulation of potassium in the vitreous humor. The authors previously have reported a chemical method for determining PMI from the predictable accumulation or clearance of the dopaminergic metabolite 3-methoxytyramine (3-MT) in the putamen of the brain. They have extended their previous study to compare directly the accuracy of determining PMI from the level of 3-MT in putamen with the level of potassium in vitreous humor. The data indicate that 3-MT is at least as accurate as, if not more accurate than, potassium accumulation in vitreous humor, although 3-MT levels can be affected by the cause of death and drugs present at the time of death. Nevertheless, determination of both the 3-MT and potassium levels can afford the most accurate method of determining PMI; preliminary nomograms for determining PMI from both variables are presented. PMID- 2918281 TI - Age estimation from quantitation of features of "chest plate" X-rays. AB - This study presents a method for estimating the age at death from the quantitation of roentgenologic features of X-ray films of chest plates obtained during routine autopsies. Multiple linear regression analysis allows estimation of coefficients of regression of features on known age-at-death individuals. The regression equation can be used in turn for age estimation of an unknown age-at death individual. The accuracy of age estimation is about +/- 8.4 years (standard error) which is in the range of previously published macroscopic methods, though the present method is much faster and simpler. PMID- 2918282 TI - Death caused by a constricting snake--an infant death. AB - A 21-month-old male was found dead in his crib. An escaped pet python snake (Python reticulatus) was found near the child on a cribside shelf. Autopsy findings included petechiae associated with asphyxial death plus puncture wounds consistent with the reptile's teeth. This report details this 1982 death of a child in Reno, Nevada, and includes illustration of the reptile's bite marks plus description of snake jaw mechanics in swallowing. PMID- 2918283 TI - Suicide by intravenous injection of cocaine. A report of three cases. AB - Death as a consequence of cocaine abuse is continuing to increase in all parts of the United States. Cocaine use may cause the development of psychosis, with subsequent expression of suicidal ideations, and potentially even successful suicide. Cocaine dependence may also cause depression in the individual who is unable to control his or her craving for the drug, and suicide may be perceived as the only solution to a desperate problem. Despite the dramatic escalation of cocaine abuse and the potential toxicity of this drug, there have been no reports within the United States of cocaine being used as the agent to accomplish a suicide. Herewith are reported three cases in which depression and desperation over cocaine dependence were the motivations for successful suicide, which was accomplished through the intravenous injection of cocaine to the point of death. True cocaine suicide is probably only identified through the presence of objective scene information that unequivocally proves suicidal intent, such as notes or letters which contain information to this effect. A careful search of the scene of death in cocaine fatalities is mandatory, and diligent application of routine scene investigation principles may reveal that suicide through the use of cocaine is more widespread than first appearances would suggest. PMID- 2918284 TI - Toolmarks and peculiar blunt force injuries related to an adjustable wrench. AB - A factory hand troubled a housewife with a money matter, and in the end he beat her to death with an adjustable wrench. The toolmarks found at the crime scene and the patterned injuries on the victim are shown in this article. PMID- 2918285 TI - Cranial suture eccentricities: a case in which precocious closure complicated determination of sex and commingling. AB - The union of the cranial sutures can follow a somewhat erratic course. While it is recognized that this can cause inaccuracies in estimating age at death, deviant closure patterns can influence assessments other than age. Premature or eccentrically fusing sutures can alter cranial growth and, therefore, shape. Such modified growth vectors can significantly influence metric analysis. A case is described in which precocious synostosis of the sagittal suture complicated determination of sex in a set of skeletalized remains. Features of the cranium and post-cranial skeleton indicated the individual was male, while the mandible, both metrically and morphologically, appeared to have come from a female. This led to the question of commingling. Techniques are described which were used to resolve these issues. PMID- 2918286 TI - Drug concentrations and driving impairment--consensus report. PMID- 2918287 TI - Validity testing of commercial urine cocaine metabolite assays: II. Sensitivity, specificity, accuracy, and confirmation by gas chromatography/mass spectrometry. AB - A comprehensive validity assessment study was performed on eight commercial urine assays for detection of cocaine use. Sensitivity, specificity, and accuracy of each assay were evaluated by analyzing, in random order and under blind conditions, specimens spiked with known drug concentrations and clinical specimens obtained from human subjects after intravenous cocaine use. Commercial assay results were compared with gas chromatography/mass spectrometry (GC/MS) assay of the same specimens for benzoylecgonine. All of the assays examined were determined to have utility in screening for cocaine use, with the exception of the KDI Quik Test, which was not a reliable test for detection of cocaine use. Major differences in sensitivity, specificity, and confirmation rate by GC/MS were noted among the assays, differences which should be taken into consideration when implementing a urine screening test for cocaine use or interpreting test results involving use of these assays. PMID- 2918288 TI - Analysis of cocaine-positive fatalities. AB - A review of all autopsy and toxicology reports for persons dying in New York City in an 11-month period found 935 persons dying with cocaine in their bodies. Cocaine-positive fatalities were more likely in the young black and Hispanic and male population. In addition to cocaine and its metabolites, heroin and other opiates were found in 39% of persons and ethanol in 33% and barbiturates and minor tranquilizers in only 2% of the deceased. Cocaine overdose was responsible for 4% of the deaths and overdose with heroin and cocaine for 12% of the deaths. Violence was often the cause of death. Thirty-eight percent died of homicide, seven percent of suicide, and eight percent from accidents. Of particular interest were 6 persons who died of acute cardiac events directly related to cocaine as well as 4 cases of ruptured dissections of the ascending aorta, and 9 cases of cerebral hemorrhage. Autopsy findings for these individuals are described, and possible mechanisms of death are discussed. PMID- 2918289 TI - Excluding a psychoactive substance use disorder in forensic psychiatric evaluations. AB - The forensic psychiatrist is sometimes asked to exclude that a person has a psychoactive substance use disorder, for example, in a security worker who has access to weapons, in a health care professional who may be alcohol/drug impaired, or in a parent, in a deprived child or custody hearing matter. After examining the data that are leading to the evaluation, these evaluations require corroborated background information to look for developmental and genetic antecedents that might be consistent with substance abuse and dependence; inquiry into the history of substance use; and an examination of areas, in which problems from substance use can occur, namely in family and other social relationships, at work, in legal settings, in physical health, and in personal and psychiatric reactions, for example, in suicidal behavior. Then a physical exam and laboratory evaluation are conducted to look for medical evidence of substance use and complications therefrom, and a mental status exam is performed and psychological testing is obtained as required, for example, a Minnesota Multiphasic Personality Inventory (MMPI) or neuropsychological testing. When such an evaluation is essentially negative, the examiner can say, within the limits of the evaluation, that a psychoactive substance use disorder does not exist. PMID- 2918290 TI - ABH antigen typing in bone tissue. AB - Results obtained from the ABH grouping of bone tissues by the absorption-elution procedure and by a recently described two-dimensional absorption-inhibition procedure are reported. Neither the elution nor the inhibition procedure alone yielded uniformly correct results. A combination procedure consisting of the use of both absorption-elution and two-dimensional absorption-inhibition is proposed for bone ABH grouping. When elution and inhibition were used in combination, specimens yielding concordant results with both techniques were correctly grouped. PMID- 2918291 TI - Amanita phalloides mushroom poisoning: a cluster of four fatalities. AB - A group of four illegal aliens had been without food for several days when they found a group of wild mushrooms growing in a field in Southern California. Each man consumed a meal of one to six fried mushrooms. Two days after eating the mushrooms, all four men developed abdominal pain, nausea, diarrhea, and intractable vomiting. Three days after consuming the mushrooms, all four were hospitalized and their clinical courses rapidly deteriorated to refractory hepatorenal failure and coma. Three of the victims died three days after admission to the hospital and the fourth died eight days after admission. The autopsy findings are presented and the mechanism of Amanita phalloides mushroom poisoning is discussed. PMID- 2918292 TI - The use of videotape to demonstrate the dynamics of bite marks. AB - Traditionally, bite mark photographs have been used to study statically a dynamic event. With the advent of the compact video camcorder, odontologists can now document bite marks on video tape and, in some instances, with the model of the suspect's dentition, may be able to record the dynamics of a bite on human flesh. A review of two cases and equipment used is discussed. PMID- 2918293 TI - Changes in the specificity of blood groups induced by enzymes from soil fungi. AB - Three strains of Cunninghamella elegance (C. elegance), Penicillium simplicissimum (P. simpl.), and Aspergillus niger (A. niger) were isolated from soil that produced the enzymes acting on blood groups A and B red cells. Culture filtrates from these fungi contained alpha-N-acetyl-D-galactosaminidase as an A decomposing enzyme, which resulted in an almost complete loss of A specificity and an enhancement of blood group H activity as measured by elution tests using monoclonal antibodies. They also contained an alpha-D-galactosidase and an alpha L-fucosidase, which partially destroyed the blood group B specific activity, but did not influence the blood group H specific activity. PMID- 2918294 TI - Computers for the small office practice: one clinician's experience. PMID- 2918295 TI - Measuring depressive symptomatology in China. AB - A study was conducted on a representative sample of 1000 residents in Tianjin, China to construct a scale of depressive symptoms. From items and criteria developed in the West and statements and expressions understood by the Chinese, a set of 26 statements was formulated. After a series of psychometric (reliability and validity) analyses, it was proposed that a set of 22 items form the Chinese Depressive Symptom Scale (CDS-22) and that a subset of 16 items (CDS-16) constitute the abbreviated version. Comparisons of the levels and patterns of symptomatology in China as measured by such scales with those found in the United States show considerable similarities. PMID- 2918296 TI - Psychosocial adjustment of Hmong refugees during their first decade in the United States. A longitudinal study. AB - Over their first decade in the United States, 100 Hmong refugees were studied on three occasions. Data included demographic characteristics, acculturation skills, traditional affiliations and pastimes, material acquisitions, psychosocial problems, and self-rating scales. In addition to a description of the data changes, a multiple regression analysis was performed. Changes demonstrated considerable evidence of acculturation, psychiatric care seeking, and greatly reduced symptom levels for several symptom complexes. However, a large minority of subjects remain illiterate, unable to speak English, generally involved with other Hmong but not with the majority society, and/or have high symptom levels on self-rating scales. Regarding symptom changes, depression, somatization, phobia, and self-esteem symptoms improved the most with time and acculturation. On the contrary, anxiety, hostility, and paranoid symptoms changed little. Multiple regression analyses indicated that strong traditional ties (e.g., large household size, being an herbal healer), older age, marital problems, and medical complaints were most associated with high symptom levels. PMID- 2918297 TI - Somatic symptom index (SSI): a new and abridged somatization construct. Prevalence and epidemiological correlates in two large community samples. AB - An abridged somatization construct (the Somatic Symptom Index) derived from the Diagnostic Interview Schedule's somatization disorder items was tested on community epidemiological samples to examine its prevalence, risk factors, and predictive value. The construct had a high prevalence (range, 4.4% to 20% compared with .03% to 0.7% for the full DSM-III somatization disorder diagnosis), was related to low socioeconomic status, female gender, older chronological age, and Hispanic ethnic background. The presence of this construct determined preferential use of medical services and predicted high indices of disability. The Somatic Symptom Index may have practical utility for clinical and community studies of somatoform phenomena. PMID- 2918298 TI - Posttraumatic stress disorder as a consequence of the POW experience. AB - To estimate the relative contributions of trauma and premorbid disposition in the development and persistence of posttraumatic stress disorder (PTSD) symptoms, we conducted structured psychiatric interviews of 62 former World War II POWs. Half these men satisfied DSM-III criteria for PTSD in the year following repatriation. Eighteen (29%) continued to meet the criteria for PTSD 40 years later. Family history of mental illness and preexisting psychopathology were at best only weakly correlated with persistent PTSD symptoms. The strongest predictors of PTSD were proportion of body weight lost and the experience of torture during captivity. This study demonstrates that former POWs frequently develop posttraumatic stress disorder and that for one half of those who develop the symptoms, they persist for over 40 years. Familial risk factors and preexisting psychopathology are superseded by the overwhelming nature of the trauma. The persistence of the symptoms for many years is a reflection of the severity of the trauma. PMID- 2918299 TI - Diagnostic and psychopharmacological treatment characteristics of 536 inpatients with posttraumatic stress disorder. AB - Descriptive information (demographic variables, DSM-III diagnoses, and medications prescribed) was obtained from the discharge summaries of 536 male veteran inpatients who received a diagnosis of posttraumatic stress disorder (PTSD) over a 4-year period. Data comparisons were also made between two types of inpatient programs (specialized PTSD vs. psychiatric ward) to control for program selection biases. Consistent with previous studies, alcohol and substance abuse and/or depression diagnoses occurred concurrently with PTSD. Diagnoses of schizophrenia were more prevalent in the psychiatric wards. Nearly one third of the total sample received an axis II diagnosis, with borderline features most common. Half of all patients received psychopharmacological treatment in addition to psychotherapy. Antidepressants, neuroleptics, and beta-blockers were prescribed most frequently. Directions for future inpatient PTSD research are offered based on the findings. PMID- 2918300 TI - Nocturnal panic. AB - The phenomenon of nocturnal panic was examined by comparing individuals with panic disorder who reported the experience of nocturnal panic (N = 37) with those who did not (N = 56). Variables that were assessed included frequency and intensity of daytime panic attacks, generalized anxiety, and responses to a standardized physiological assessment. In addition, the most recent nocturnal panic was rated on measures of intensity, duration, and circumstances. Nocturnal panic occurred in individuals who were equally avoidant and distressed as individuals who did not experience nocturnal panic. However, nocturnal panickers experienced daytime panics and general somatic sensations more frequently than other panickers. The similarity of nocturnal panic to sleep apnea, dream-induced anxiety attacks, and night terrors is discussed. The nature of nocturnal panic is described within the context of an explanatory model that combines behavioral and physical factors. PMID- 2918301 TI - Masochistic personality disorder. A prototype analysis of diagnosis and sex bias. AB - The Work Group of the American Psychiatric Association to revise DSM-III in 1985 proposed a new personality disorder titled Masochistic Personality Disorder (MPD). This study concerns the clinical relevance and possible sex bias of MPD. The study was performed with clinicians who analyzed 15 case histories, five of which represented masochistic personality. The results led to the rejection of two hypotheses: a) masochistic personalities can be subsumed under existing DSM III categories and b) there is a sex bias in the diagnostic use of MPD. PMID- 2918302 TI - Possible mechanisms of inhibition and activation of rat N-acetyltransferase (EC 2.3.1.5.) by cations. AB - The possible mechanisms of inhibition and activation of various cations on rat pineal N-acetyltransferase (NAT) were elucidated. Copper was found to be a partial mixed noncompetitive inhibitor of NAT with respect to both substrates and this inhibition can be considered to result primarily from impairment of tryptamine (serotonin) binding to the enzyme. Both calcium and magnesium were found to activate NAT by a similar mechanism, with calcium being more effective than magnesium. It appears that the activation results from cation binding to the enzyme causing an increased affinity of tryptamine (serotonin) for binding to NAT and therefore enhancing catalytic activity. The monovalent cations, potassium and sodium, activated NAT by a similar mechanism which differed from the caused by the divalent cations. It can be suggested that tryptamine (serotonin) binds to the enzyme followed by the monovalent cation which enhances binding of the acetyl donor and thereby promotes catalysis. At high potassium or sodium concentration the affinity of acetyl coenzyme A for NAT begins to decrease suggesting that excess monovalent cations can be inhibitory and may represent an endogenous regulatory mechanism controlling in vivo NAT activity. It is possible that certain cations may be involved in regulation of melatonin synthesis although the physiological significance of such modulation remains unknown. PMID- 2918303 TI - Probable mechanism of catalysis of pineal gland hydroxyindole-O-methyltransferase (HIOMT) from rainbow trout (Salmo gairdneri). AB - Activity of trout pineal HIOMT was found to increase with increase in incubation temperature from 5 to 40 degrees C although the activation energy remained constant over this range. From examination of the effects of the products of HIOMT catalysis on the enzyme it was apparent that the catalytic mechanism was ordered Bi-Bi with S-adenosylmethionine as the obligatory first substrate. Trout HIOMT was found to methylate all the common pineal hydroxyindoles with hydroxytryptophol having the greatest affinity for the enzyme. The pH optimum for trout HIOMT was found to be about pH 9.0 although routine use of a pH of 7.9 is recommended to limit potentially deliterious effects caused by degradation of S adenosylmethionine at elevated pHs. PMID- 2918304 TI - Cholinesterases in the cerebrospinal fluid, plasma, and erythrocytes of patients with Alzheimer's disease. AB - In patients with probable Alzheimer's disease and in controls, acetyl- and butyrylcholinesterase activities were studied in cerebrospinal fluid (CSF) and plasma, and acetylcholinesterase activity of erythrocytes was determined. In addition, the molecular forms of acetylcholinesterase were measured in CSF. Severely demented patients had significantly lower acetylcholinesterase (p less than 0.01) and butyrylcholinesterase (p less than 0.05) activities in CSF than the controls had, but the activities of these enzymes in plasma and erythrocytes were within the same range in both groups. Acetylcholinesterase and butyrylcholinesterase activities in the CSF of mildly demented patients did not differ from control values. The ratio of the intermediate molecular form of acetylcholinesterase to the light molecular form of the enzyme did not differ significantly between patients with Alzheimer's disease and controls. According to our results, AChE levels were lower in the CSF of severely demented patients, but both light and intermediate molecular forms were affected. PMID- 2918305 TI - The ratio of acetylcholinesterase to butyrylcholinesterase influences the specificity of assays for each enzyme in human brain. AB - A single-vial extraction radiometric assay was used to measure acetylcholinesterase and butyrylcholinesterase in human post-mortem brain tissue. Data are presented regarding the differential inhibition of acetylcholinesterase and butyrylcholinesterase in several brain areas from a case of Alzheimer's disease and a case without neuropsychiatric disease. The results indicate that neither enzyme is entirely specific for its substrate, and the necessity for using inhibitors depends upon the ratio of acetylcholinesterase to butyrylcholinesterase in a particular sample. PMID- 2918306 TI - Postmortem- and cryostability of the potassium-evoked release of [3H]5 hydroxytryptamine from rat cerebral cortical miniprisms. AB - A prerequisite for the study of neurotransmitter release from human brain autopsy samples with histories of different diseases is that the cryo- and postmortem stability of the release process is good. In the present study, the effect of post-mortem delay and of storage at -70 degrees C by the "slow freeze--fast thaw" method of Hardy et al. [J Neurochem (1983) 40: 608-614] (which allows for the retention of metabolic activity of the tissue after the storage and thawing) of rat cerebral cortex samples upon the release of [3H]5-hydroxytryptamine ([3H]5 HT) from prelabelled miniprisms has been investigated. Storage of samples at -70 degrees C by this method resulted in samples that accumulated less [3H]5-HT but showed an increased sensitivity to the Ca2+-dependent releasing properties of K+ when compared with "fresh" samples. On the other hand, the sensitivity of the K+ evoked release to the inhibitory effects of the serotoninergic agonist 5-methoxy N,N-dimethyltryptamine were reduced by storage. The effects on [3H]5-HT accumulation and on K+-evoked release were due mainly to the freeze-thaw procedure, the length of storage at -70 degrees C having only a minor influence on these parameters. A post-mortem interval of 5 hours at either +4 or +22 degrees C prior to storage of the tissue reduced the K+-evoked release of tritium, but did not affect the accumulation of [3H]5-HT or the inhibitory effects of 5-methoxy-N,N-dimethyltryptamine on the K+-evoked release over and above the effects produced by the storage per se. PMID- 2918307 TI - Intracerebral dialysis monitoring of striatal dopamine release and metabolism in response to L-dopa. AB - We have used intracerebral dialysis to monitor the striatal extracellular fluid (ECF) in rats with unilateral lesions of the nigrostriatal dopamine (DA) pathway. Dialysis samples were collected before and after L-dihydroxy-phenylalanine (L DOPA) administration both in the presence and absence of carbidopa, an extracerebral DOPA decarboxylase (DDC) inhibitor. The baseline ECF levels of DA, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) were always higher in the intact than in the lesioned striata. In the normal striata, dopamine (DA) concentrations increased following L-DOPA administration. Pretreatment with carbidopa prolonged the duration of the DA increase. In the lesioned striata, DA levels increased following L-DOPA administration only in animals pretreated with carbidopa. Following L-DOPA administration, striatal HVA and DOPAC levels increased considerably more in animals not pretreated with carbidopa than they did in pretreated animals. This increase was particularly marked in the lesioned striata and leads us to conclude that extracerebrally produced HVA and DOPAC can enter the brain extracellular space. PMID- 2918308 TI - Oral aspartame and plasma phenylalanine: pharmacokinetic difference between rodents and man, and relevance to CNS effects of phenylalanine. Short note. AB - The ingestion of aspartame, a phenylalanine-containing dipeptide, raises plasma phenylalanine levels. These increments are much greater in humans than rats, because the rat hydroxylates phenylalanine five times faster than man. Accordingly, dose comparisons of aspartame (or phenylalanine) between humans and rats have usually been corrected by a factor of five. Recently, a correction factor of sixty has been proposed (Wurtman and Maher, 1987); the rationale is based on a novel calculation of competitive phenylalanine transport into brain. An analysis of the logic behind this postulation reveals there to be no basis for accepting the higher dose conversion of 60 between rat and man. PMID- 2918309 TI - Regional alterations in blood-to-brain transfer of alpha-aminoisobutyric acid and sucrose, after chronic administration and withdrawal of dexamethasone. AB - The effect of dexamethasone administration and withdrawal was studied with respect to blood-brain barrier function. The tracers alpha-[3H]aminoisobutyric acid (AIB) (MW 104) and [14C]sucrose (MW 342), which have a low permeability across the intact endothelium, were simultaneously injected intravenously in rats treated with dexamethasone and placebo-treated control animals or in rats in which dexamethasone treatment was discontinued 3 days before the experiment. Unidirectional transfer constants (Ki) were determined in discrete brain regions. Steroid administration reduced the rate of influx of AIB and sucrose, whereas discontinuation of drug resulted in an increased permeability. These findings suggest that when exposure to glucocorticoids is prolonged, the efficiency of medical treatment of CNS diseases may decrease due to reduction of drug delivery to CNS. Thus, these experimental findings may have particular importance in the clinical setting of drug administration when considering the combination of steroids with other drugs, and may aid in understanding better the pathogenesis of some types of brain edema seen in patients from whom corticosteroid therapy has been withdrawn. PMID- 2918310 TI - Effect of ouabain applied by intrastriatal microdialysis on the in vivo release of dopamine, acetylcholine, and amino acids in the brain of conscious rats. AB - In the present study we have applied a brain microdialysis technique to investigate the effects of ouabain infusion on the release of dopamine, acetylcholine, and amino acids from striatal neurons in freely moving rats. Ouabain caused an increase in the dialysate levels of dopamine; its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC); and the amino acids glutamate, aspartate, taurine, glycine, alanine, serine, asparagine, and threonine. The ouabain-induced increase in dopamine was dose dependent and explosive (100-fold at an infusion concentration of 1 mmol/L) and contrasted strongly with the small effect of the glycoside on the output of DOPAC. We investigated the nature of ouabain-induced transmitter release by determining its sensitivity to coinfusion with tetrodotoxin or the calcium antagonist Mg2+. In the case of dopamine two mechanisms of ouabain-induced release could be established. At lower infusion concentrations ouabain induced an exocytotic type of release whereas at higher concentrations the release was probably carrier mediated. In the case of amino acids we noticed a calcium-independent release which was nerve impulse flow dependent in the case of glutamate and aspartate and impulse flow independent in the case of alanine, serine, glycine, threonine, and asparagine. Ouabain induced a decrease in the release of acetylcholine and glutamine. PMID- 2918311 TI - Concentrations of tryptoline and methtryptoline in rat brain. AB - Combined gas chromatography-mass spectrometry and gas chromatography-tandem mass spectrometry have been used to identify and quantify tryptoline, methtryptoline, 5-hydroxytryptoline, and 5-hydroxymethtryptoline as their heptafluorobutyryl derivatives in extracts of rat brain. Tryptoline and methtryptoline were identified on the basis of their retention times and mass spectral characteristics: they were reliably detected in brain tissue extracts without interference from artifactual formation; their whole brain concentrations ranged between 0.2 and 3 ng/g; and they had a similar neuroanatomical distribution, with the highest concentrations in the cerebellum and the cortex. Smaller quantities of 5-hydroxytryptoline and 5-hydroxymethtryptoline were also identified on the basis of their retention times and mass spectral characteristics. However, the significance of this finding is unclear, because these two compounds were accompanied by larger quantities of their tetradeuterated analogues formed from tetradeuterated-5-hydroxytryptamine added at the time of tissue homogenization; this result suggests that formation of 5-hydroxytryptoline and 5 hydroxymethtryptoline occurred during tissue homogenization, sample preparation, or both. PMID- 2918312 TI - Clonidine prevents transient loss of noradrenaline in response to cholinergic hypofunction induced by ethylcholine aziridinium (AF64A). AB - Intracerebroventricular injection of ethylcholine aziridinium (AF64A) (2 nmol/ventricle) induced a considerable decrease in the level of acetylcholine (ACh) in hippocampus (from 21.14 +/- 0.84 to 10.04 +/- 0.59 pmol/mg of tissue; p less than 0.001) 4 days after application. The reduction of cholinergic function was accompanied by a decrease in the level of noradrenaline (NA) (from 1.96 +/- 0.08 to 1.41 +/- 0.06 pmol/mg of tissue; p less than 0.001). Two days after administration of AF64A (1 or 2 nmol/ventricle), the dose-dependent decrease in NA level was associated with an increase in the level of its major metabolite, 3 methoxy-4-hydroxyphenylglycol (MHPG), resulting in a considerable increase in the MHPG/NA molar ratio (from 0.84 +/- 0.06 to 1.62 +/- 0.17; p less than 0.002). Chronic treatment of AF64A-injected rats with clonidine (0.02-0.2 mg/kg, i.p., every 8-12 h) had no significant effect on the loss of ACh content, whereas the decrease in NA content in hippocampus was completely prevented. Clonidine induced aggressive behavior in the AF64A-treated rats, in contrast to sedation in vehicle injected rats. The response to clonidine under these experimental conditions and the increased MHPG/NA molar ratio in response to AF64A suggest that the transient loss of NA content following AF64A administration results from increased NA release. The increased noradrenergic activity in hippocampus may be linked to the reduction of tonic inhibitory cholinergic input. These results are discussed in relation to possible implications for senile dementia of the Alzheimer type. PMID- 2918313 TI - Synaptosomal "membrane-bound" choline acetyltransferase is most sensitive to inhibition by choline mustard. AB - The objectives of the present study were to validate the presence of cytoplasmic and membrane-associated pools of choline acetyltransferase (ChAT) in rat brain synaptosomes, and to evaluate inhibition of these different forms of the enzyme by the nitrogen mustard analogue of choline, choline mustard aziridinium ion (ChM Az). The relative distribution of ChAT and lactate dehydrogenase (LDH) was followed in subfractions of synaptosomes to establish whether ChAT activity associated with salt-washed presynaptic membranes represents membrane-bound protein rather than cytosolic enzyme trapped within undisrupted synaptosomes or revesiculated membrane fragments. The percentage of total synaptosomal ChAT activity (14%) recovered in the final membrane pellet always exceeded that of LDH (6%), lending support to the hypothesis that much of the ChAT associated with the membranes was a membrane bound form of the enzyme. Incubation of purified synaptosomes with ChM Az led to irreversible inhibition of ChAT activity; this loss of enzyme activity could not be accounted for by lysis of nerve terminals during incubation in the presence of the mustard analogue. Subfractionation of the ChM Az-treated nerve terminals revealed that the membrane-bound form of ChAT was inhibited to the greatest extent, followed by the ionically membrane associated enzyme, with the activity of the water-solubilized enzyme not differing significantly from control. Preparation of the synaptosomal ChAT subfractions from untreated nerve terminals prior to incubation with varying concentrations of ChM Az or naphthylvinylpyridine revealed that under these conditions water-solubilized, ionically membrane-associated, and detergent solubilized membrane-bound pools of ChAT were not differentially inhibited by either compound.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918314 TI - Effect of glucose starvation on glucose transport in neuronal cells in primary culture from rat brain. AB - The regulation of glucose transport into cultured brain cells during glucose starvation was studied. On glucose deprivation for 40 h, 2-deoxy-D-glucose (2-DG) uptake was stimulated twofold in neuronal cells but was not changed significantly in astrocytes. On refeeding, the increased activity of neuronal cells rapidly returned to the basal level, an observation indicating that the effect of glucose starvation was reversible. The increase was due solely to change in the Vmax, a finding suggesting that the number of glucose transporters on the plasma membrane is increased in starved cells. Cycloheximide inhibited this increase. In the presence of cycloheximide, the activity of 2-DG uptake of starved cells remained constant for 12 h and then slowly decreased, whereas that of fed cells decreased rapidly. These findings suggest that glucose starvation regulates glucose transport by changing the rate of net synthesis of the transporter in neuronal cells in culture. PMID- 2918315 TI - Catecholamine content changes in brain regions of spontaneously hypertensive rats under immobilization stress. AB - We compared the effect of immobilization stress on noradrenaline (NA) and 3 methoxy-4-hydroxyphenylethyleneglycol (MHPG) content in two brain regions- diencephalon and pons-medulla oblongata--in young and adult spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). In SHR, NA content decreased with time after the onset of the stress, whereas levels of its metabolite MHPG increased. In WKY, NA and MHPG showed no change. The MHPG/NA ratio in both regions increased relative to the duration of the stress in SHR, whereas it remained almost constant in WKY. The rate of increase in the ratio was much higher in the diencephalon of adult (12-week-old) than of young (4-week-old) SHR. In SHR, NA turnover in the brain is readily affected by environmental stress, and these changes in the noradrenergic system may induce or sustain hypertension. PMID- 2918316 TI - Tellurium-induced neuropathy: metabolic alterations associated with demyelination and remyelination in rat sciatic nerve. AB - Rats fed a diet containing 1.25% elemental tellurium initiated on postnatal day 20 undergo a transient neuropathy characterized by synchronous demyelination of peripheral nerves. In sciatic nerve, the extent of demyelination was maximal after 5 days of tellurium exposure; there was a loss of 25% of the myelin, as assayed by concentration of myelin-specific P0 protein. Tellurium-induced alterations in the metabolic capacity of Schwann cells were examined by measuring the synthesis of myelin lipids in vitro in isolated sciatic nerve segments. Exposure to tellurium resulted in an early marked decrease of approximately 50% in overall incorporation of [14C]acetate into lipids, with a preferential depression in synthesis of cerebrosides, cholesterol, and ethanolamine plasmalogens (components enriched in myelin). Most dramatically, within 1 day of initiation of tellurium exposure, there was a profound increase in [14C]acetate derived radioactivity in squalene; 23% of incorporated label was in this intermediate of cholesterol biosynthesis, compared to less than 0.5% in controls. In association with the remyelinating phase seen after 5 days of tellurium exposure, synthesis of myelin components gradually returned to normal levels. After 30 days, metabolic and morphologic alterations were no longer apparent. We suggest that the sequence of metabolic events in sciatic nerve following tellurium treatment initially involves inhibition of the conversion of squalene to 2,3-epoxysqualene, and that this block in the cholesterol biosynthesis pathway results, either directly or indirectly, in the inhibition of the synthesis of myelin components and breakdown of myelin. PMID- 2918317 TI - Hippocampal membranes contain a neurotrophic activity that stimulates cholinergic properties of fetal rat septal neurons cultured under serum-free conditions. AB - Primary cultures of fetal rat septal neurons were used to identify a membrane associated cholinergic neurotrophic activity. Under serum-free culture conditions, approximately 98% of the septal cells are neurons, and approximately 6% of the neurons are cholinergic as determined immunocytochemically. Crude membranes prepared from rat hippocampal homogenates stimulate choline acetyltransferase (ChAT) activity in treated septal neurons. The membrane associated trophic activity is apparent at lower protein concentrations than activity present in the soluble fraction and is unevenly distributed in various brain regions; it is highest in hippocampus and striatum and negligible in cerebellum. Membrane trophic activity is developmentally regulated, is heat and trypsin sensitive, and increases the rate of expression of ChAT in septal neurons. Upon gel filtration chromatography of a high-salt membrane extract, trophic activity elutes as a broad peak in the 500 kilodalton (kD) molecular mass range. Stimulation of septal neuronal ChAT activity by either crude membranes or partially purified preparations is not inhibited by antibodies against nerve growth factor (NGF), and its maximal activity is additive to maximally active doses of NGF. The results indicate that hippocampal membranes contain cholinergic neurotrophic activity which may be important for the development of septal cholinergic neurons. PMID- 2918318 TI - ATP-evoked Ca2+ mobilisation and prostanoid release from astrocytes: P2 purinergic receptors linked to phosphoinositide hydrolysis. AB - Astrocyte cultures prelabelled with either [3H]inositol or 45Ca2+ were exposed to ATP and its hydrolysis products. ATP and ADP, but not AMP and adenosine, produced increases in the accumulation of intracellular 3H-labelled inositol phosphates (IP), efflux of 45Ca2+, and release of thromboxane A2 (TXA2). Whereas ATP stimulated 3H-IP accumulation was unaffected, its ability to promote TXA2 release was markedly reduced by mepacrine, an inhibitor of phospholipase A2 (PLA2). ATP evoked 3H-IP production was also spared following treatment with the cyclooxygenase inhibitor, indomethacin. We conclude that ATP-induced phosphoinositide (PPI) breakdown and 45 Ca2+ mobilisation occurred in parallel with, if not preceded, the release of TXA2. Following depletion of intracellular Ca2+ with a brief preexposure to ATP in the absence of extracellular Ca2+, the release of TXA2 in response to a subsequent ATP challenge was greatly reduced when compared with control. These results suggest that mobilisation of cytosolic Ca2+ may be the stimulus for PLA2 activation and, thus, TXA2 release. Stimulation of alpha 1-adrenoceptors also caused PPI breakdown and 45 Ca2+ efflux but not TXA2 release. The effects of ATP and noradrenaline (NA) on 3H-IP accumulation were additive, but their combined ability to increase 45Ca2+ efflux was not. Interestingly, in the presence of NA, ATP-stimulated TXA2 release was reduced. Our data provide evidence that functional P2-purinergic receptors are present on astrocytes and that ATP is the first physiologically relevant stimulus found to initiate prostanoid release from these cells. PMID- 2918319 TI - Cloning of a putative neuronal nicotinic acetylcholine receptor subunit. AB - A cDNA clone was isolated from a rat superior cervical ganglion cDNA library with an oligonucleotide that hybridized to muscle-like nicotinic acetylcholine receptor (nAChR) subunit cDNA. The deduced amino acid sequence possesses characteristics expected of a nAChR subunit that does not bind acetylcholine, in addition to distinctive features such as unique cysteine residues and N-linked glycosylation sites. PMID- 2918320 TI - The effect of local recurrence on survival time in adult high-grade soft tissue sarcomas. AB - Data gathered on 262 adults with high-grade soft tissue sarcoma, operated on at the same institution for curative intent, were used to study formally, and to quantitate for the first time, the relationship between local recurrence of the tumor and survival time. Using Cox's proportional hazards model with a time dependent covariate representing the local recurrence of the tumor, it was found that local recurrence is significantly associated with a shorter survival time (estimated relative risk (relative hazard) = 2.5, p less than 0.0001). The estimated 5 yr survival rate and median survival time for patients without a local recurrence were 44% and 42 months, respectively, while the corresponding figures for patients with a local recurrence were only 26% and 28 months. Hence, a local recurrence resulted in a relative decline in the estimated 5 yr survival rate of 41%. This strong relationship continued to hold even after adjusting for several other important, time-independent prognostic variables (stage, type of surgery, type of resection, signs of sarcomatous skin invasion, and presence of postoperative fever) in a multivariable analysis. Local control of high-grade soft tissue sarcomas is vitally important for successful management of these patients. PMID- 2918321 TI - Effects of framing and level of probability on patients' preferences for cancer chemotherapy. AB - Although most clinicians agree that patients should be informed about treatment alternatives, little is known about the way patients perceive probabilistic information about treatment outcomes and how it influences the choices they make. The purpose of this study was to examine the influence of level and framing of probability on preferences for cancer treatment alternatives in which tradeoffs between quantity and quality of life are made. 129 healthy volunteers and 154 cancer patients indicated their preferences for a toxic treatment over a non toxic treatment at varying survival probabilities. Subjects responded to questions in one of three randomly assigned conditions: (1) a positive frame in which the probability of survival was given; (2) a negative frame in which the probability of dying was given; and (3) a mixed frame in which the probability of surviving and dying were both given. The cancer patients' preferences for the more effective toxic treatment was significantly stronger than the healthy volunteers. Both groups were significantly influenced by the level of probability that was presented. Preferences for the toxic treatment were weaker when the chance of survival dropped below 50%. This weakening preference below 50% survival was enhanced for subjects who responded in the negative frame. A negative frame or probability level below 0.5 would seem to stimulate a "dying mode" type of value system in which quality of life becomes more salient in decision making than quantity of life. The implications in eliciting informed consent from patients are discussed. PMID- 2918322 TI - Prognosis of gallstones with mild or no symptoms: 25 years of follow-up in a health maintenance organization. AB - Two-hundred ninety-eight patients with gallstones accompanied by mild or nonspecific symptoms, 123 with asymptomatic gallstones, and 46 with nonfunction on cholecystogram and mild or nonspecific symptoms were followed in the setting of a health maintenance organization for up to 25 years after diagnosis. In a life-table analysis, complications (severe events) developed in about 1% per year of patients with visualized gallstones and in about 2% per year of patients with nonfunction. During each of the first 5 years after diagnosis, all events, both severe and non-severe (including surgery for continuing mild symptoms) occurred in about 6% of the patients with mild symptoms accompanying either gallstones or nonfunction, and in about 4% of patients with asymptomatic gallstones. The annual probabilities for all events tended to decrease as length of follow-up increased. Among patients with stones and mild symptoms, women were more apt to develop any event than men (p = 0.02) and more obese patients were more likely to develop severe events than those who were thinner (p = 0.05). The patients in this study are probably more representative of outpatients with gallstones seen by most primary care physicians than are most groups investigated previously for prognosis. Their event rates are sufficiently similar to those used in published decision analyses, that they should not alter previous conclusions that early elective cholecystectomy will have little positive or negative effect on average life expectancy of patients with gallstones. PMID- 2918323 TI - An investigation of a reported cancer cluster in Randolph, Massachusetts. AB - An increasingly common public health problem is the perception that disease incidence has increased or a cluster of disease has occurred in a community. In most cases, the disease of concern is cancer and a local hazardous waste site or other environmental problem is involved. These problems can be difficult to investigate and public health officials are frequently criticized for their inability to address community concerns. This paper reports a case study of such a situation occurring in the Barlett-Green Acres (BGA) neighborhood of Randolph, Massachusetts. Study data were obtained by interviews in households of persons belonging to a list of alleged cancer cases initially supplied by residents and supplemented using records available in town and state public health offices. One objective of the investigation was to develop methods that may be of value in similar situations arising in other communities. From a list of names compiled prior to and during the investigation, 45 incident cases of cancer were identified and found suitable for analysis. An additional four cases were added from the Massachusetts Cancer Registry. The analysis showed the existence of a cancer cluster, but overall cancer incidence and mortality in the BGA neighborhood were not elevated. Residence history, disease site, and other features of the cancer cases were investigated using methods less sensitive to incomplete reporting than total incidence. No unusual features of the cancer data other than the initiating cluster were identified and no environmental hazard likely to impact the BGA neighborhood was discovered, hence we conclude that the most likely cause of the cancer cluster was random variation in cancer rates. PMID- 2918324 TI - Epidemiologic evidence of perinatal influence in the etiology of adult cancers. AB - Using data from 5489 cancer patients and 2647 patients without cancer we investigated whether parental age at the birth of the patient or the patient's rank within his sibship was related to the risk of cancer during adulthood. An increase of 10 years in maternal age was associated with an increase of 24% for the incidence of breast cancer (odds ratio = 1.24%; 95% CI = 1.09-1.41); the corresponding increase for paternal age was 19% (odds ratio = 1.19; 95% CI = 1.07 1.33). There was some evidence that the age of each parent may make an independent contribution to the risk of breast cancer. For certain types of genito-urinary cancers, the risk was higher when the parents were relatively young at the birth of the patient. These cancers included tumors arising in the prostate (odds ratios = 0.71 and 0.55 for maternal and paternal ages, respectively), testis (odds ratios = 0.57 and 0.52), penis (odds ratios = 0.37 and 0.45), kidney (odds ratios = 0.66 and 0.60), and bladder (odds ratio = 0.79 and 0.85). The associations for cancer of the prostate and bladder were stronger among patients who were diagnosed at a relatively young age. No statistically significant effects were found for birth order relative to adult cancers. The authors conclude that environmental factors that affect the parents or that operate in the perinatal period may have stronger influences on the incidence of adult cancers than have been previously recognized. PMID- 2918325 TI - Survival in multiple sclerosis. AB - Survival from onset of symptoms was calculated for two series of MS patients, a population-based epidemiologic series from southern Lower Saxony of 224 cases, and a revised hospital series of 1429 cases from 11 neurologic centers throughout the Federal Republic of Germany. Median survival for the epidemiologic series was 35-42 years, with no finer estimate possible. Observed survival was 3/5 expected survival after 35 years of illness. Survival in this series was similar to that from two other population-based reports. No significant difference was found between the sexes, though patients with onset at age 35 + had a significantly shorter survival than those with onset at age under 35 years. The much larger hospital series, where median survival was 30 years, demonstrated significant differences separately favoring females and young onsets. However, the ratios of observed to expected survival from population life tables were strikingly similar among all four subgroups defined by sex and age at onset. While overall there is a substantial reduction in the expectation of life in MS, the differential survival by sex and age appears to be a reflection of the expected survival by sex and age per se, and not that of the disease. PMID- 2918326 TI - On estimating survival; a tale of two censors. PMID- 2918327 TI - Are risk factors for CHD the same at different ages. PMID- 2918328 TI - Risk factors in middle age that predict early and late onset of coronary heart disease. AB - Twelve biological and lifestyle characteristics measured in a group of 5919 middle aged men free of clinical coronary heart disease (CHD), stroke and cancer were analyzed for differences in predicting early and late onset of new cases of definite CHD (non-fatal myocardial infarction and fatal CHD) over a 12-year follow-up period. Among these men, 151 cases of definite CHD occurred early (under age 60) and 135 cases occurred later in life (age 60 and over). Serum triglyceride was the only risk factor that was an independent predictor of early onset disease and not of late onset disease. While cigarette smoking was a predictor for both onset groups, the effect of smoking was greater in people who developed CHD earlier in life. Systolic blood pressure, alcohol intake, serum cholesterol and serum glucose were independent predictors for both onset groups, with no difference in effect between groups. The findings indicate that it is possible for some factors to affect CHD risk differently in terms of premature vs delayed onset of disease. The findings for serum triglyceride may account for some of the inconsistencies in reports regarding it as an independent risk factor for CHD. In general, however, most of the characteristics studied here had a similar effect on both early and late onset and thus remain important in the prevention of both premature and late onset of CHD. PMID- 2918329 TI - Phase I trial of intramuscularly administered tumor necrosis factor in patients with advanced cancer. AB - A phase I trial of intramuscularly administered recombinant human tumor necrosis factor (rTNF) was conducted in 19 adult patients with advanced solid tumors. The agent was administered daily for up to five consecutive days every other week for two to four courses. Doses of rTNF ranged from 5 to 200 micrograms/m2/d. Dose limiting toxicities were encountered at doses greater than 100 micrograms/m2/d. Toxicities included tenderness, erythema and induration at the site of injection, fatigue, fever, chills, headache, anorexia, nausea, vomiting, and diarrhea. Moderate to marked reductions in WBC and platelet counts were observed regularly at the highest dose levels, but none were clinically significant. Hepatic enzyme elevation was seen frequently, and two patients developed hyperbilirubinemia. Only one of seven patients treated with doses greater than 100 micrograms/m2/d completed the planned course of therapy. Even at the highest dose levels, serum concentrations of rTNF could only rarely be detected in the serum. No therapeutic responses were observed. The maximal tolerated dose (MTD) of rTNF in this trial was 150 micrograms/m2/d, administered for two courses. PMID- 2918330 TI - Minimal residual disease in acute lymphoblastic leukemia detected by immune selection and gene rearrangement analysis. AB - We have developed an assay for the detection of malignant residual cells in the bone marrow from patients with B- or T-lineage acute lymphoblastic leukemia (ALL) in clinical remission. This assay involves an immune selection step followed by immunoglobulin or T-cell receptor gene rearrangement analysis and allows the detection of one contaminating tumor cell out of 1,000 normal bone marrow cells. We have examined the bone marrow of 11 patients with adult ALL in remission over a 24-month period. Five patients relapsed in the bone marrow and one in the CNS. The assay allowed the detection of minimal residual disease in four of five patients that subsequently relapsed in the bone marrow, 1.5 to 9 months before the relapse became morphologically and clinically manifest. Residual disease was not found in the bone marrow from patients in continuous remission and from the single patient who relapsed in the CNS. We conclude that the ability of the assay described here to detect minimal residual disease with high specificity can provide information for further understanding of the biology of ALL and hopefully for the clinical management of patients with this disease. PMID- 2918331 TI - A long-term follow-up study of survival in stage I (T1N0M0) and stage II (T1N1M0) breast carcinoma. AB - This study was undertaken to investigate the long-term survival and the probability of "cure" in a group of 644 patients treated by mastectomy for T1 breast carcinoma. After a median follow-up of 18.2 years, 23% were dead of recurrent breast carcinoma, 3% were alive with recurrent disease, and 74% had not experienced a recurrence. The probability of recurrence was directly related to the initial extent of the disease. Overall, 16% of recurrences and 25% of deaths due to disease occurred in the second decade of follow-up. The proportion of recurrences detected in the second decade was inversely related to the stage of the primary tumor at diagnosis. When stratified by tumor size, T1N0M0 patients with tumors 1.0 cm or less in diameter had a significantly better 20-year recurrence-free survival (86%) than did T1N0M0 patients with tumors 1.1 to 2.0 cm (69%). When observed and expected survival curves were compared by the method of Brinkley and Haybittle, it appeared that 80% of T1N0M0 patients with tumors 1 cm or less might be cured at 20 years, whereas for those in the 1.1- to 2-cm group, the proportion cured was indeterminate, but might be as high as 70%. A potentially cured group could not be identified among T1N1M0 patients, but an estimated 52% of these patients did not have a recurrence within the nearly 20 year follow-up period. These data are important when one considers the proper role of adjuvant therapy for stage I disease. Patients with tumors larger than 1 cm and those with axillary lymph node metastases may have an improved recurrence free survival as a result of systemic adjuvant treatment, while women in the T1N0M0 group with an especially favorable recurrence-free survival, particularly those with tumors 1 cm in diameter or smaller, might be spared adjuvant therapy. PMID- 2918332 TI - Breast conservation versus mastectomy: distress sequelae as a function of choice. AB - Between 1981 and 1984, 93 stage I and II breast cancer patients were entered onto a trial at the National Cancer Institute (NCI) randomizing patients to excisional biopsy plus radiation v mastectomy. Between 1984 and 1987, 98 stage I and II breast cancer patients were entered onto a behavioral study in Pittsburgh, approximately 70% of whom elected to have breast conservation surgery. Patients at both sites were assessed three to five days postsurgery, and again at 3 month's follow-up, using a well-validated mood measure, the Profile of Mood States (POMS). There were no demographic or disease differences between the two samples. In the Pittsburgh sample, using a repeated measures multivariate analysis of covariance (MANCOVA) analysis, after adjusting for menopausal status and radiotherapy and chemotherapy toxicity, the conservation group was psychologically worse off (F = 2.7, P less than .03). For example, they were significantly more distressed over time (F = 5.5, P less than .02), and more depressed in general (F = 9.2, P less than .005). Using Karnofsky ratings, the two groups were identical in terms of disability at 3-month's follow-up. In contrast, for the NCI patients participating in the randomized trial, after adjusting for chemotherapy and radiotherapy treatments, reported overall distress decreased over time (F = 17.4, P less than .0001) for all patients, irrespective of treatment group, and the between-groups MANCOVA was not significant. Thus, when comparing the two samples, when "choice" played a major role, the conservation patients were psychologically worse off--at least at 3-month's follow-up.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918333 TI - Results of surgery for obstructing carcinomatosis of gastrointestinal, pancreatic, or biliary origin. AB - Results of operation for obstructing carcinomatosis of gastrointestinal (GI), pancreatic, or biliary origin were reviewed to assess relief of symptoms, management of re-obstruction, and duration of hospitalization. A retrospective review (1977 to 1986) identified 89 patients, 59 (66%) of whom had tumors originating in the colon, and 19 (21%) in the stomach. Normal bowel function was restored for a median of 102 days in 66 patients (74%) and all but four (94%) were discharged. Forty-one (46%) patients remained unobstructed until death. Twenty-three (26%) were not relieved by operation and died a median of 33 days later (P less than .005). Forty-eight (81.4%) of the 59 colon cancer patients and ten (52.6%) of 19 with gastric cancer (P less than .05) were benefited by the operation, although comparison of duration of function was less striking (P less than .1). In-hospital mortality was 13% and complications occurred in 44%. Obstruction recurred in 38% of those relieved by the initial operation. Normal bowel function was restored in six (46%) of 13 patients undergoing a second laparotomy (median, 158 days) and in six of 13 (46%) treated with nasogastric suction. Obstruction recurred again in four of the latter six patients (median, 39 days). Hospitalization averaged 31 days (median, 25 days) for the first procedure and 41 days (median, 39 days) for patients operated for recurrent obstruction. These results justify laparotomy for intestinal obstruction in known or suspected carcinomatosis, particularly of colonic origin, if performance status is compatible with a reasonable quality of life. PMID- 2918334 TI - Chronic daily administration of oral etoposide--a phase I trial. AB - In this phase I study, we administered etoposide (VP-16) orally for 21 consecutive days to patients with advanced refractory cancers. All patients had received previous chemotherapy, and 50% of patients had received more than one combination regimen. When given for 21 consecutive days, the maximum-tolerated dose of oral VP-16 was 50 mg/m2/d. Myelosuppression was the dose-limiting toxicity, and occurred between days 21 and 28. In most patients, blood counts had recovered sufficiently by day 35 to begin another 3-week course. WBC count nadirs of less than 1,000/microL occurred in four of 20 courses at this dose, and three patients required hospitalization for treatment of neutropenia and fever. Alopecia occurred in most patients; gastrointestinal (GI) and other toxicities were uncommon. Five of 16 patients with measurable tumor had partial responses of 3 to 4 months duration. Four of these five patients had malignancies that are usually unresponsive to VP-16 when administered by previously investigated schedules. This method of VP-16 administration is well tolerated, convenient, and may optimize antitumor efficacy by exploiting the schedule dependency of this drug. Phase II studies are necessary to define the level of activity of this schedule of VP-16. PMID- 2918335 TI - Activity of coumarin and cimetidine in metastatic renal cell carcinoma. PMID- 2918336 TI - Prognostic factors related to response to chemotherapy in metastatic breast cancer. PMID- 2918337 TI - Neural coding of gustatory information in the thalamus of Macaca mulatta. AB - 1. Extracellular action potentials were recorded from single neurons in the parvicellular division of the ventroposteromedial (VPMpc) nucleus of the thalamus of restrained, but alert, Old World monkeys during gustatory, tactile, and thermal stimulation of the oral cavity. In contrast to previous reports in anesthetized or paralyzed rats, the spontaneous activity of these neurons was brisk and their evoked responses robust. 2. Each of 50 taste-responsive neurons was tested with 1.0 M sucrose, 0.1 M NaCl, 0.003 M HCl, and 0.001 M QHCl before other concentrations of the same stimuli were used. Sucrose, which was effective in 80% of the neurons tested, evoked the largest responses of the 4 standard gustatory stimuli (16.1 spikes/s). The average response to NaCl, an effective stimulus for 44% of the neurons in the sample, was 7.5 spikes/s. HCl and QHCl, which few neurons responded to, typically evoked smaller responses. 3. Most of the neurons tested showed monotonic intensity-response (I-R) functions. The power functions showed about the same degree of compression (range = 0.39-0.53), which has been described previously for brain stem neurons in anesthetized rodents. Only 9.1% of the responses were inhibitory, and there was no tendency for these responses to be associated with either specific neurons or stimuli. These data suggest that quality coding of gustatory information in the thalamus is not radically different from that seen among lower-order neurons in other species. 4. Through the use of hierarchical cluster analysis, it was possible to divide the neuron sample into 2 groups, one of which consisted of sucrose-best neurons that had an average entropy value of 0.56. The neurons in the other group, though more heterogeneous, showed either primary or side-band sensitivity to NaCl. The average breadth of responsiveness of the 50 thalamic neurons as described by the entropy coefficient was 0.73. 5. In addition to gustatory neurons, tactile (n = 15), thermal (n = 1), and nonresponsive (n = 25) neurons also were located within VPMpc. An additional 48 neurons that could not be classified as either sensory or motor in nature, inhibited their bursting spontaneous discharge just prior to the onset of fluid stimulation. Only 2 of these neurons demonstrated differential chemical sensitivity. The presence of these nongustatory neurons within the thalamic taste area suggests that the traditional characterization of VPMpc as a gustatory relay may understate its role in ingestive behavior and ignore other noningestive functions of the area. PMID- 2918338 TI - Patterns of spontaneous discharge in primate spinothalamic neurons. AB - 1. The spontaneous discharge of 30 spinothalamic tract (STT) neurons in the lumbosacral spinal cord of anesthetized monkeys was studied. Interval, correlation, and spectral analyses were performed. 2. Three patterns of discharge were found; these were referred to as the SP1, SP2, and SP3 patterns. 3. The SP1 group had moderately regular discharge trains that were devoid of short-interval spike bursts. 4. The SP2 group had spike trains dominated by short-interval bursts without evidence of low-frequency rhythmicity. 5. The SP3 group had spike trains with features of both the SP1 and SP2 groups. 6. Some correlations were found between the mean discharge rate and stimulus-response classes previously defined by our group (25). Correlations were deduced from a parent data set of 221 STT neurons. Type 1 neurons, which were driven primarily by tactile afferents, were found to have significantly lower mean rates than other "within neuron" groups. On the other hand, type C neurons, which had strong input from afferents signalling pressure and noxious stimuli, were found to have significantly higher mean rates than all other "across-neuron" classes. 7. A weak relationship was found between the pattern of discharge and the within-neuron stimulus-response classification. Neurons with a largely tactile coding orientation (types 1 and 2) were most frequently of the SP1 and SP2 classes, whereas neurons with a more prominent nociceptive input (types 3 and 4) were most frequently of the SP2 and SP3 classes. No relationship was apparent between discharge pattern and the across-neuron classes. PMID- 2918339 TI - Somatotopic organization of forelimb representation in cervical enlargement of raccoon dorsal horn. AB - 1. Somatosensory representation of the forelimb in the dorsal horn of spinal segments C5-T2 was examined in 13 North American raccoons anesthetized with pentobarbital sodium. Single- or multiple-unit responses to light mechanical stimulation were recorded at a total of 504 loci, which were subsequently reconstructed from stained, transverse sections. From these, dorsal view maps of forelimb representation in Rexed's laminae III and IV were synthesized. 2. There was a shifting, serial overlap of representations of different forelimb regions in both the rostrocaudal and mediolateral axes of the dorsal horn. The rostrocaudal progression of receptive fields was from preaxial forelimb to forepaw to postaxial forelimb, whereas the mediolateral progression was from the volar glabrous forepaw toward the trunk. 3. Representations of the glabrous surfaces of the digits and palm pads showed considerable overlap, with the digital representations extending more laterally, but the palmar representations extending more rostrally and caudally. One-third of all recording loci were devoted exclusively to glabrous skin representation. 4. Comparison with results of earlier studies in raccoons indicates that representation of a given digit or palm pad is more restricted in rostrocaudal extent in the dorsal horn than in the dorsal roots, and that, compared with various nuclear regions of the dorsal column-medial lemniscal system, the glabrous surfaces of the forepaw are underrepresented in the dorsal horn. 5. The results suggest that there is a dorsoventral modular organization of forelimb representation in the dorsal horn. These wedge-shaped modules from larger aggregates which represent major body subdivisions and which course sinuously in the rostrocaudal dimension. PMID- 2918340 TI - Spinocervical tract neurons responsive to light mechanical stimulation of the raccoon forepaw. AB - 1. The extracellular activity of 45 antidromically identified spinocervical tract (SCT) neurons responsive to light mechanical stimulation of the glabrous surfaces of the forepaw was examined in raccoons anesthetized with pentobarbital sodium. An additional seven neurons had peripheral receptive fields (RFs) located on hairy skin of the forelimb, and three had deep RFs. 2. All recording sites were histologically verified as falling within Rexed's laminae III and IV in spinal cord segments C6-T1. Antidromic conduction velocities of the 55 neurons ranged between 8.3 and 64.2 m/s. 3. Units with glabrous skin RFs were classified according to their response to a maintained mechanical stimulus as either rapidly adapting (n = 39) or slowly adapting (n = 6). Of 11 cells tested, 2 displayed enhanced responses to noxious stimuli and were classed as multireceptive. 4. RF areas were significantly smaller on digits (range = 0.4-45.0 mm2) than on palm pads (range = 5.6-76.0 mm2), and comparable in size to RF areas previously reported in raccoon cuneate nuclear cells (32). 5. RA neurons fell into three distinct categories with respect to the relationship between instantaneous spike frequency during displacement ramp stimulation, and ramp velocity, steep functions (as defined by the value of power function exponents), flat functions, and discontinuous functions; SA neurons fell into two categories, continuous, and discontinuous. 6. The results, in conjunction with those of previous studies, lead to two major conclusions: 1) raccoon and primate spinocervicothalamic systems are more similar to each other than either is to that of the cat and 2) the ability of the raccoon SCT to convey information from the glabrous skin of the forepaw regarding characteristics of light mechanical stimuli is at least as precise as that of neurons of the dorsal column-medial lemniscal system. PMID- 2918341 TI - Responses to parallel fiber stimulation in the guinea pig dorsal cochlear nucleus in vitro. AB - 1. Parallel fibers of the guinea pig dorsal cochlear nucleus (DCN) were electrically stimulated at the pial surface of the nucleus in a brain-slice preparation. Extracellular field potentials produced by the parallel fibers and postsynaptic cells, and the response of single units were identified and characterized. Responses were compared with those reported for stimulation of parallel fibers in the cerebellum and to those seen with electrical stimulation of the auditory nerve. 2. Stimulation of the DCN parallel fibers generates a consistent set of extracellular field potentials. In layer 1 of the DCN, a short latency triphasic wave (P1(1)-N1(1)-P2(1)) is followed by a slower negative wave (N2(1)). The onset phase of the N2(1) often exhibits a small positive notch (P2a1). In layer 2, an initial triphasic wave (P1(2)-N1(2)-P2(2)) is followed by a short-latency negative wave (N2(2)) and a slower positive wave (P3(2)). The N1(2) is approximately coincident with the N1(1), whereas the P3(2) is coincident with N2(1). The falling phase of the P3(2) is sometimes interrupted by a brief negative deflection (N3(2)). These field potentials are similar, but not identical to those reported for parallel fiber stimulation in the cerebellum in vivo (15). These responses differ substantially from those produced in the DCN by electrical stimulation of the auditory nerve (50). 3. Low-calcium solutions and pharmacologic manipulations were used to separate pre- and postsynaptic response components in the field potential records. When the slice is bathed in a low calcium solution the P2a1, N2(1), N2(2), P3(2), and the brief late deflections are abolished. However, the P1(1)-N1(1)-P2(1) and P1(2)-N1(2)-P2(2) remain unaffected. A similar separation of pre- and postsynaptic components can be achieved with 100 microM adenosine or 0.5 mM kynurenic acid. It is concluded that the P1(1)-M1(1)-P2(1) wave is the compound action potential of the unmyelinated parallel fibers, whereas the longer-latency field potential components are generated postsynaptically. 4. The conduction velocity of the parallel fiber volley was measured to be 0.30 m/s at the pial surface, in a line approximately parallel to the strial axis of the nucleus. Mapping experiments reveal that the spread of the P1(1)-N1(1)-P2(1) is greatest along the strial axis, and more limited in the orthogonal direction. 5. Single units were recorded in layer 2. At a distance of 500-700 microns from the stimulating electrode, the latencies of single-unit discharges fall between 2.5 and 4 ms, at the time of the N2(2).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2918342 TI - Topographic and directional organization of visual motion inputs for the initiation of horizontal and vertical smooth-pursuit eye movements in monkeys. AB - 1. The goal of our study was to determine the properties of the visual inputs for pursuit eye movements. In a previous study we presented horizontal target motion along the horizontal meridian and showed that targets were more effective if they moved across the center of the visual field. We have now analyzed the topographic weighting of the inputs for pursuit in greater detail, using targets that moved in all directions and across a wide area of the visual field. 2. Monkeys were rewarded for tracking targets that started at 48 positions in the visual field. The initial positions were spaced equally around 4 circles that were centered at the position of fixation and had radii of 3, 6, 9, and 12 degrees. Targets moved horizontally or vertically at 30 degrees/s. We measured the smooth eye acceleration in the first 80 ms after the initiation of pursuit, before there had been time for visual feedback to affect the position or velocity of the retinal images from the target. 3. For both horizontal and vertical target motion, there were major differences between the early and late intervals in the first 80 ms of pursuit. In the first 20 ms eye acceleration was largely independent of initial target position. In later intervals eye acceleration decreased sharply as a function of initial target eccentricity. The later intervals also showed a pronounced toward/away asymmetry such that the initiation of pursuit was more vigorous for target motion toward than for motion away from the horizontal or vertical meridian. 4. Comparison of the topographic organization of the middle temporal visual area (MT) with our data on pursuit suggests that the topography of cortical maps is smoothed when the visual signals are transmitted to the pursuit system. For example, the superior visual hemifield is underrepresented in cortical motion processing areas, but target motion in the superior and inferior visual hemifields is equally effective for the initiation of pursuit. 5. We investigated the directional organization of the visual inputs for pursuit by presenting targets that started at 6 degrees eccentric and moved in 16 different directions. Horizontal target motion always evoked larger eye accelerations than did vertical target motion. Target motion in oblique directions evoked intermediate values of eye acceleration. 6. Our data show two classes of variation in pursuit performance. First, some subjects showed ideosyncratic variations that were restricted to one hemifield or one direction of target motion. We attribute these variations to differences among subjects in the physiology of visual pathways.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2918343 TI - The contribution of articular receptors to proprioception with the fingers in humans. AB - 1. Whether joint receptors contribute demonstrably to proprioception has remained uncertain. Therefore, we tested whether an articular contribution to movement sense could be revealed if the total sensory input available to signal joint movement were reduced by eliminating movement signals from muscles. With a reduced sensory input, whatever contribution articular receptors made to proprioception ought to assume a greater-than-normal importance, and any effect of eliminating articular inputs should become more apparent. The distal interphalangeal joint of the middle finger was used, because the muscles could be decoupled from this joint by positioning the fingers to slacken the tendons. 2. To further enhance the possibility for observing an effect of eliminating articular contributions, we planned to test movement sense at positions of the joint in which the articular receptors would be most active. However, the response properties of receptors in primate finger joints were unknown, so we examined activity of receptors in finger joints of monkeys prior to testing humans. 3. Activity of receptors in interphalangeal joints of monkeys was measured over a wide range of positions before and during local anesthesia of the joint. Little response was seen over intermediate positions, but activity increased as the joint approached full flexion or full extension in much the same manner as responses previously observed with receptors in the knee, elbow, wrist, and hip joints. Local anesthetic injected into the joint space abolished the nerve activity. 4. Proprioception was tested in humans before and during local anesthesia of the joint using a movement-detection paradigm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918344 TI - Cable properties of spinal cord motoneurons in adult and aged cats. AB - 1. The electrophysiological properties of spinal cord alpha-motoneurons were investigated in adult cats (1-3 yr old) and old cats (14-15 yr old) using intracellular recording techniques. Voltage transients following depolarizing pulses of current were analyzed according to the procedure described by Ito and Oshima (15). The input resistance of each cell, together with the passive electrical time constants, were used to estimate the electrotonic length and total cell capacitance of each motoneuron. 2. Adult and old motoneurons both exhibited an undershoot of the membrane potential following the cessation of a subthreshold depolarizing current pulse (15). The average time constant for the decay of this undershoot in membrane potential was statistically indistinguishable in motoneurons of adult and aged animals. 3. The average membrane time constant of motoneurons in aged cats was 19% longer than that of motoneurons in adult cats. 4. The average total cell capacitance of motoneurons in aged cats was 16% smaller than that of motoneurons in adult cats. 5. The average electrotonic length of old motoneurons was statistically indistinguishable from that of motoneurons in adult cats. 6. From these results, we conclude that there is an age-dependent increase in the membrane resistance and an age-dependent decrease in cell surface area of alpha-motoneurons of the lumbar spinal cord in aged cats. Both of these phenomena are believed to contribute to the age-dependent increase in input resistance that has been previously reported to occur in motoneurons in aged cats (18). PMID- 2918345 TI - Distribution of combination-sensitive neurons in the ventral fringe area of the auditory cortex of the mustached bat. AB - 1. The orientation sound (pulse) of the mustached bat, Pteronotus parnellii parnellii, consists of long constant-frequency components (CF1-4) and short frequency-modulated components (FM1-4). The auditory cortex of this bat contains several combination-sensitive areas: FM-FM, DF, VA, VF, and CF/CF. The FM-FM area consists of neurons tuned to a combination of the pulse FM1 and the echo FMn (n = 2, 3, or 4) and has an echo-delay (target-range) axis. Our preliminary anatomical studies with tritiated amino acids suggest that the FM-FM area projects to the dorsal fringe (DF) area, which in turn projects to the ventral fringe (VF) area. The aim of our study was to characterize the response properties of VF neurons and to explore the functional organization of the VF area. Acoustic stimuli delivered to the bats were CF tones, FM sounds, and their combinations mimicking the pulse emitted by the mustached bat and the echo. 2. Like the FM-FM and DF areas, the VF area is composed of three types of FM-FM combination-sensitive neurons: FM1-FM2, FM1-FM3, and FM1-FM4. These neurons show little or no response to a pulse alone, echo alone, single CF tone or single FM sound. They do, however, show a strong facilitative response to a pulse-echo pair with a particular echo delay. The essential components in the pulse-echo pair for facilitation are the FM1 of the pulse and the FMn of the echo.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918346 TI - Force output of cat motor units stimulated with trains of linearly varying frequency. AB - 1. A relation between stimulation frequency and muscle force is usually determined with stimulus trains of constant frequency and described as a single valued sigmoid curve. This relationship fails to explain a number of features of rate coding. 2. Single motor units were isolated in medial gastrocnemius or soleus muscles of cats deeply anesthetized with pentobarbital sodium. Motor units were classified as fast or slow. Each unit was stimulated with a train whose frequency varied linearly from less than 3 pulses per second (pps) to 20% above the unit's fusion frequency and back to about 3 pps with a period of 5 s. 3. All motor units showed a marked hysteresis during frequency-varying stimulation. A greater force was produced when frequency was decreasing than when it was increasing. The force output of each unit remained nearly maximal as stimulus frequency declined from its maximum to about one-half of the unit's fusion frequency; force rapidly declined with further decreases in frequency. The force frequency relation could change with each trial as frequency increased but was highly reproducible when frequency decreased. This suggested a strategy by which central nervous system (CNS) control could maximize the force at any discharge rate and produce a predictable force-frequency relation. 4. Posttetanic potentiation, motor unit slowing, and a preload which causes a motor unit to operate on the negatively sloping portion of the length-tension curve may each contribute to the observed hysteresis under certain circumstances. None can explain why hysteresis was consistently seen in all motor units. A time-dependent rate of tension development and decay together with a catchlike property can account for all of the properties of hysteresis and appeared to be the primary cause of hysteresis in fully potentiated motor units. PMID- 2918347 TI - Measurement of passive membrane parameters with whole-cell recording from neurons in the intact amphibian retina. AB - 1. Whole-cell recordings have been obtained from intact, photoactive retinal neurons using patch-clamp electrodes in the amphibian superfused retina eyecup preparation. 2. After removal of the vitreous humor from the surface of the retina, using a collagenase with low tryptic activity, high-resistance seals (1 10 G omega) could be formed between the patch pipette and the cell membrane by applying mild suction to the pipette. Additional suction broke the membrane patch and provided continuity between the low-resistance pipette and the interior of the neuron. 3. Measurements of input resistance and time constant were obtained from bipolar, amacrine, and ganglion cells. Assuming the membrane capacitance was 1 microF/cm2, time constant data were used to derive the specific membrane resistance. The average specific membrane resistance for the inner retinal neurons in our sample was 68,000 omega.cm2. 4. Analysis of the charging curve induced by a brief current pulse applied to the soma was used to analyze the average electrotonic length of dendrites. The charging curves of some ganglion cells were well represented by a single exponential, suggesting that they were essentially isopotential. 5. The voltage decay along an equivalent cylinder model of a ganglion cell was calculated, using the experimentally obtained values of membrane resistance to compute decay of steady-state voltages along the dendritic tree. The calculations indicate that with the high membrane resistance values implied by this study, the electrotonic length of dendritic cables were short, and there may be relatively little attenuation of the synaptic potentials irrespective of their location along the dendritic tree. PMID- 2918348 TI - An evaluation of the role of identified interneurons in triggering kicks and jumps in the locust. AB - 1. We have used intracellular recording and staining techniques to examine the importance of certain identified interneurons within the system responsible for triggering kicks and jumps in the locust, Locusta migratoria. In particular, our study focused on a pair of metathoracic interneurons called the M-neurons. These cells make strong inhibitory connections to hind-leg flexor motoneurons and are thought to play a key role in the termination of flexor activity which causes kicks and jumps to be triggered (8, 20, 24). 2. Simultaneous recordings from M neurons and flexor motoneurons during bilateral hindleg kicks revealed that in most cases the onset of the M-neuron's high-frequency discharge coincided precisely with the start of the flexor's rapid repolarization. This result demonstrated that M's activity had the correct timing to be involved in the triggering process and so confirmed suggestions made in previous studies. At times, however, the flexor motoneurons began to repolarize slowly prior to the first spike in the M-neuron, indicating that triggering must involve other neurons and perhaps also an additional mechanism such as a reduction of flexor excitation. 3. The sufficiency and necessity of the M-neurons for triggering kicks were tested by experiments involving intracellular current injections. The application of a brief pulse of depolarizing current to an M-neuron, in order to evoke a burst of spikes in the cell prior to the time it would normally have become active, caused extension of the ipsilateral leg to be triggered prematurely but did not influence the motor program in the contralateral leg. This effect was only observed when the discharge frequency evoked artificially in the M-neuron was greater than that seen during natural performance of the behavior. Even then, the repolarization produced in the flexor motoneurons by the current pulses was not the same as occurs normally. We conclude that under natural circumstances the M-neurons, by themselves, are not sufficient to trigger kicks. 4. When the usual discharge in an M-neuron was prevented by the injection of hyperpolarizing current, both legs were still able to kick. This lack of necessity of the M-neurons confirms that additional neurons must be involved in the triggering process. The rate of repolarization of the flexor motoneurons during kicks in which M activity had been abolished was slower and more variable than is seen in normal kicks but this did not appear to alter the timing of leg extension.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2918349 TI - W-and Y-cells in the C layers of the cat's lateral geniculate nucleus: normal properties and effects of monocular deprivation. AB - 1. Previous studies have shown that rearing with monocular visual deprivation (MD) produces a loss of Y-cells and a reduction in spatial resolution among X cells in layers A and A1 of the cat's dorsal lateral geniculate nucleus (dLGN). However, there have been no studies of the effects of visual deprivation on the function of the retinogeniculate W-cell pathway, which terminates in the C layers of the dLGN. It also is not known if Y-cells in the C layers are affected by MD in the same way as Y-cells in the A layers. These questions were addressed by the present experiment. 2. Single-cell recordings were made from the C layers of 5 normal adult cats (112 cells) and from the nondeprived (94 cells) and deprived (95 cells) C layers in 10 cats monocularly deprived by lid suture for 3-7 yr. The cells were classified as X, Y, or W on the basis of their receptive-field properties and responses to electrical stimulation of the optic chiasm. In addition, quantitative measures were made of responses to sine-wave gratings of different spatial frequencies. 3. Receptive-field organization, receptive-field center size, spatial and temporal linearity to counterphased sine-wave gratings, and latency to optic chiasm stimulation were similar for C-layer cells in normal cats and in the deprived and nondeprived layers of MD cats. On the basis of these properties, 23% of normal layer-C cells were classified as Y-cells and 72% were classified as W-cells. The Y-cells tended to be located in the magnocellular division of layer C and most (though not all) W-cells were in the parvocellular division. Normal layers C1 and C2 contained almost exclusively W cells. The incidence of Y and W cells was similar to normal in the nondeprived and deprived C-layers of MD cats. 4. In normal cats, W cells typically had the lowest amplitude first-harmonic (F1) response rates to drifting sine-wave gratings. However, many W cells gave quite brisk responses and, overall, there was no significant difference between F1 response amplitudes of Y and W cells. Response amplitudes of Y- and W-cells in the deprived and nondeprived C-layers of MD cats were not significantly different from normal. 5. Normal Y- and W-cells tended to have low optimal spatial frequencies (0.2 c/deg or lower) and spatial resolutions (generally 0.4-1.6 c/deg) to drifting sine-wave gratings.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2918350 TI - Deficits of visual attention and saccadic eye movements after lesions of parietooccipital cortex in monkeys. AB - 1. Visual attention is often profoundly disturbed in humans after damage to the cortex of the posterior parietal lobe, particularly of the minor hemisphere, with some patients being totally unaware of visual stimuli in the hemifield of extrapersonal space contralateral to the cortical damage. This severe form of visual inattention is usually called contralateral neglect and has occasionally been reported following posterior parietal lesions in monkeys. However, in monkeys, only qualitative observations have been published and those reports are not in agreement concerning the severity of the deficit. The present experiments were designed to measure quantitatively the amount of disruption of selective visual attention which is produced by lesions of posterior parietal and parietooccipital cortical lesions in monkeys. 2. Five monkeys were trained to visually fixate and follow with their gaze a small visual stimulus as it suddenly moved varying distances (8, 16, or 24 degrees) from the midline into the left or right visual hemifields. Two animals then received a unilateral cortical lesion limited to the inferior parietal lobule (IPL). Three animals received unilateral lesions which included both the inferior parietal lobule and a portion of adjacent dorsal prestriate cortex (IPL-PS). 3. Visual inattention is commonly divided into two levels of severity. The more severe form, contralateral neglect, is the complete absence of behavioral response to a stimulus in the visual field contralateral to hemisphere damage. The less severe deficit, usually called visual extinction, is a tendency to ignore the contralateral of two visual stimuli when they appear simultaneously and symmetrically placed with respect to the center of the subject's surroundings. The five monkeys in this study were tested on a stimulus paradigm which simultaneously measured the severity of visual neglect and also the amount and duration of visual extinction which were produced by the cortical lesions. 4. All monkeys displayed contralateral visual extinction after unilateral posterior parietal or parietooccipital lesions. Three of the five monkeys showed a reversal of the visual extinction after a second, symmetrical lesion was placed in the opposite hemisphere. No monkey showed evidence of full-blown contralateral neglect after lesions limited to the parietooccipital cortex, either in the formal testing situation or during informal neurological examinations. The severity of the observed inattention did not appear to be related to the size of the cortical lesions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2918351 TI - Impulse activity of a crayfish motoneuron regulated its neuromuscular synaptic properties. AB - 1. Previous studies have demonstrated that initial transmitter release, fatigability, and the morphology of identified crayfish neuromuscular synapses adapt to long-term changes in motoneuron impulse activity. 2. Experiments were performed to determine whether these long-term, adaptive alterations in neuromuscular synaptic physiology are triggered by changes in neuromuscular synaptic activity, muscle activity, or neuronal impulse activity. The fast closer excitor of the crayfish claw, a phasic motoneuron, was studied. Either the central or the peripheral region of the motoneuron was selectively stimulated in vivo by blocking impulse activity midway along the motor axon with localized application of tetrodotoxin and stimulating either central or distal to the blocked region. 3. Neither muscle activity nor transmitter release from the neuromuscular synapses was required to trigger the changes in synaptic physiology. Stimulation central to the block induced changes in neuromuscular transmission that included a long-lasting decrease in initial transmitter release and increased fatique resistance. 4. Because peripheral stimulation also produced decreased initial transmitter release, it appears that increased impulse activity in either region of the motoneuron can produce the synaptic changes. These results along with earlier findings suggest that neuronal depolarization induces adaptive, long-term changes in synapses. 5. These results are discussed in relation to findings at vertebrate and invertebrate synapses. PMID- 2918352 TI - Long-lasting reduction of excitability by a sodium-dependent potassium current in cat neocortical neurons. AB - 1. The function and ionic mechanism of a slow outward current were studied in large layer V neurons of cat sensorimotor cortex using an in vitro slice preparation and single microelectrode voltage clamp. 2. With Ca2+ influx blocked, a slow relaxation ("tail") of outward current followed either (1) repetitive firing evoked for 1 s or (2) a small 1-s depolarizing voltage clamp step that activated the persistent Na+ current of neocortical neurons, INaP. When a depolarization that activated INaP was maintained, an outward current gradually developed and increased in amplitude over a period of tens of seconds to several minutes. An outward tail current of similar duration followed repolarization. The slow outward current was abolished by TTX, indicating it depended on Na+ influx. 3. With Ca2+ influx blocked, the onset of the slow Na+-dependent outward current caused spike frequency adaptation during current-evoked repetitive firing. Following the firing, the decay of the Na+-dependent current caused a slow afterhyperpolarization (sAHP) and a long-lasting reduction of excitability. It also was responsible for habituation of the response to repeated identical current pulses. 4. The Na+-dependent tail current had properties expected of a K+ current. Membrane chord conductance increased during the tail, and tail amplitude was reduced or reversed by membrane potential hyperpolarization and raised extracellular K+ concentration [( K+]0). 5. The current tail was reduced reversibly by the K+ channel blockers TEA (5-10 mM), muscarine (5-20 microM), and norepinephrine (100 microM). These agents also resulted in a larger, more sustained inward current during the preceding step depolarization. Comparison of current time course before and after the application of blocking agents suggested that, in spite of its capability for slow buildup and decay, the onset of the Na+ dependent outward current occurs within 100 ms of an adequate step depolarization. 6. With Ca2+ influx blocked, extracellular application of dantrolene sodium (30 microM) had no clear effect on the current tail or the corresponding sAHP.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2918353 TI - Norepinephrine selectively reduces slow Ca2+- and Na+-mediated K+ currents in cat neocortical neurons. AB - 1. The effects of norepinephrine (NE) and related agonists and antagonists were examined on large neurons from layer V of cat sensorimotor cortex ("Betz cells") were examined in a brain slice preparation using intracellular recording, constant current stimulation and single microelectrode voltage clamp. 2. Application of NE (0.1-100 microM) usually caused a small depolarization from resting potential; hyperpolarizations were rare. Application of NE reversibly reduced rheobase and both the Ca2+- and Na+-dependent portions of the slow afterhyperpolarization (sAHP) that followed sustained firing evoked by constant current injection. The faster Ca2+-dependent medium afterhyperpolarization (mAHP), the fast afterhyperpolarization (fAHP), the action potential, and input resistance were unaffected. 3. The changes in excitability produced by NE application were most apparent during prolonged stimulation. The cells exhibited steady repetitive firing to currents that were formerly ineffective. The slow phase of spike frequency adaptation was reduced selectively and less habituation occurred during repeated long-lasting stimuli. The relation between firing rate and injected current became steeper if firing rate was averaged over several hundred milliseconds. 4. During voltage clamp in TTX, NE application selectively reduced the slow component of Ca2+-mediated K+ current. The faster Ca2+-mediated K+ current was unaffected, as were two voltage-dependent, transient K+ currents, the anomalous rectifier and leakage conductance measured at resting potential. Depolarizing voltage steps in the presence of Cd2+ revealed an apparent time- and voltage-dependent increase of the persistent Na+ current after NE application. The voltage-clamp results suggested ionic mechanisms for all effects seen during constant current stimulation except the depolarization from resting potential. The latter was insensitive to Cd2+ and TTX and occurred without a detectable change in membrane conductance. 5. NE application did not alter Ca2+ spikes evoked in the presence of TTX and 10 mM TEA. Inward Ca2+ currents examined during voltage clamp in TTX (with K+ currents reduced) became slightly larger after NE application. We conclude that NEs reduction of the slow Ca2+-mediated K+ current is not caused by reduction of Ca2+ influx. 6. Effects on membrane potential, rheobase, and the sAHP were mimicked by the beta-adrenergic agonist isoproterenol, but not by the alpha-adrenergic agonists clonidine or phenylephrine at higher concentrations.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2918354 TI - Temporal coding of envelopes and their interaural delays in the inferior colliculus of the unanesthetized rabbit. AB - 1. The difference in the time of arrival of a sound at the two ears can be used to locate its source along the azimuth. Traditionally, it has been thought that only the on-going interaural temporal disparities (ITDs) produced by sounds of lower frequency (approximately less than 2 kHz) could be used for this purpose. However, ongoing ITDs of low frequency are also produced by envelopes of amplitude-modulated (AM) tones. These ITDs can be detected and used to lateralize complex high-frequency sounds (1, 8, 12, 15, 22, 24, 26). Auditory neurons synchronize to the modulation envelope, but do so at progressively lower modulation frequencies at higher levels of the auditory pathway. Some neurons of the cochlear nucleus synchronize best to frequencies as high as 700 Hz, but those of the inferior colliculus (IC) exhibit their best synchrony below 200 Hz. Even though synchrony to higher modulation frequencies is reduced at higher levels of the auditory pathway, is information about ITDs retained? 2. We answered this question by extracellularly recording the responses of neurons in the IC of the unanesthetized rabbit. We used an unanesthetized preparation because anesthesia alters the responses of neurons in the IC to both monaurally presented tones and ITDs. The unanesthetized rabbit is ideal for auditory research. Recordings can be maintained for long periods, and the acoustic stimulus to each ear can be independently controlled. 3. We studied the responses of 89 units to sinusoidally AM tones presented to the contralateral ear. For each unit, we recorded the response at several modulation frequencies. The degree of phase locking to the envelope at each frequency was measured using the synchronization coefficient. Two measures were used to assess the range of modulation frequencies over which phase locking occurred. The "best AM frequency" was the frequency at which we observed the greatest phase locking. The "highest AM frequency" was the highest frequency at which significant phase locking (0.001 level) was observed. We could not assess synchrony to ipsilateral AM tones directly, because most units did not respond to ipsilateral stimulation. 4. We studied the sensitivity of 63 units to ITDs produced by the envelopes of AM tones. Sensitivity to ITDs was tested by presenting AM tones to the two ears that had the same carrier frequency, but modulation frequencies that differed by 1 Hz. Units that were sensitive to ITDs responded to this stimulus by varying their response rate cyclically at the difference frequency, i.e., 1 Hz.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2918355 TI - Monaural and binaural response properties of neurons in the inferior colliculus of the rabbit: effects of sodium pentobarbital. AB - 1. We studied the effects of sodium pentobarbital on 22 neurons in the inferior colliculus (IC) of the rabbit. We recorded changes in the sensitivity of these neurons to monaural stimulation and to ongoing interaural time differences (ITDs). Monaural stimuli were tone bursts at or near the neuron's best frequency. The ITD was varied by delivering tones that differed by 1 Hz to the two ears, resulting in a 1-Hz binaural beat. 2. We assessed a neuron's ITD sensitivity by calculating three measures from the responses to binaural beats: composite delay, characteristic delay (CD), and characteristic phase (CP). To obtain the composite delay, we first derived period histograms by averaging, showing the response at each stimulating frequency over one period of the beat frequency. Second, the period histograms were replotted as a function of their equivalent interaural delay and then averaged together to yield the composite delay curve. Last, we calculated the composite peak or trough delay by fitting a parabola to the peak or trough of this composite curve. The composite delay curve represents the average response to all frequencies within the neuron's responsive range, and the peak reflects the interaural delay that produces the maximum response. The CD and CP were estimated from a weighted fit of a regression line to the plot of the mean interaural phase of the response versus the stimulating frequency. The slope and phase intercept of this regression line yielded estimates of CD and CP, respectively. These two quantities are thought to reflect the mechanism of ITD sensitivity, which involves the convergence of phase-locked inputs on a binaural cell. The CD estimates the difference in the time required for the two inputs to travel from either ear to this cell, whereas the CP reflects the interaural phase difference of the inputs at this cell. 3. Injections of sodium pentobarbital at subsurgical dosages (less than 25 mg/kg) almost invariably altered the neuron's response rate, response latency, response pattern, and spontaneous activity. Most of these changes were predictable and consistent with an enhancement of inhibitory influences. For example, if the earliest response was inhibitory, later excitation was usually reduced and latency increased. If the earliest response was excitatory, the level of this excitation was unaltered or slightly enhanced, and changes in latency were minimal. 4. The neuron's response pattern also changed in a predictable way. For example, a response with an inhibitory pause could either change to a response with a longer pause or to a response with an onset only.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2918356 TI - A differential synaptic input to the motor nuclei of triceps surae from the caudal and lateral cutaneous sural nerves. AB - 1. Postsynaptic potentials (PSPs) were recorded in 115 triceps surae motoneurons of 10 chloralose-anesthetized adult cats (spinal cord intact), upon electrical stimulation of the caudal and lateral cutaneous sural nerve branches (CCS and LCS, respectively). 2. With twice threshold (2T) stimulation of CCS, excitatory PSPs (EPSPs) were the predominant effect in 95% of all medial gastrocnemius (MG) motoneurons tested (min. central latency 1.5 ms; mean 2.4 ms). In only a few MG cells was the EPSP followed by an inhibitory postsynaptic potential (IPSP) and in only one cell was an IPSP the sole effect. Increasing the stimulus intensity to 5T tended to enhance both the later EPSP and IPSP components, with less change in the amplitude or latency of the earliest EPSPs. 3. In lateral gastrocnemius (LG) and soleus (SOL) motoneurons, 2T CCS stimulation led to either inhibition or no potential change in the majority of cells tested: EPSPs were the predominant effect in only 15 and 30% of LG and SOL cells, respectively (min. central latency 2.5 ms; mean 3.0 ms) and rarely occurred without subsequent inhibition. Again, increasing the stimulus intensity to 5T had more of an effect on later rather than earlier PSP components. 4. A predominance of depolarization in MG motoneurons but not in SOL motoneurons is in agreement with previous findings that CCS excitation is more powerful in "fast type" triceps surae motoneurons. However, the strong predominance of hyperpolarizing effects of CCS stimulation in the present LG population is evidence that such an organization does not transcend triceps surae motor nuclei as a whole. 5. Postsynaptic effects of LCS stimulation at 2T were frequently weak or absent but increasing the stimulus intensity to 5T produced predominant inhibition in 71% of all triceps surae motoneurons studied (n = 107). Of the few cells which did receive excitation from this nerve, most were MG, a few were SOL, and none were LG. These EPSPs occurred more frequently at 5T than at lower stimulation strengths. 6. The results indicate that excitation produced by electrical stimulation of the ipsilateral CCS nerve occurs preferentially in the MG portion of triceps surae and with the shortest central latencies. Effects of LCS stimulation are largely inhibitory throughout the motor nuclei comprising triceps surae but even here, the presence of excitation occurs more frequently in MG. A comparison of these results with those in other reports is discussed. PMID- 2918357 TI - Thalamocortical response transformation in the rat vibrissa/barrel system. AB - 1. Extracellular single-unit recordings and controlled whisker stimuli were used to compare response properties between cells in the "barreloids" of the thalamic ventrobasal complex and those in the cytochrome oxidase-rich centers of the "barrels" in the first somatic sensory cortex. Individual vibrissae were deflected alone or in paired combination involving the neuron's maximally excitatory whisker and an adjacent one in the same or neighboring whisker rows. Quantitative data were derived from 135 thalamocortical unit's (TCUs), 242 "regular-spike" barrel units (RSUs), and 16 "fast-spike" barrel units (FSUs) recorded in 26 normal adult rats. 2. Compared with TCUs, RSUs displayed lower rates of spontaneous activity and responded less vigorously to whisker stimuli. Proportionally, more than twice as many TCUs as RSUs responded in slowly adapting fashion to at least one angular direction of whisker displacement. Discharges of slowly adapting TCUs were approximately 3.5 times greater than those of slowly adapting RSUs. 3. Proportionally, about twice as many TCUs than RSUs responded selectively to whisker movements in different angular directions. 4. Cells in the thalamus responded more vigorously to a larger number of whiskers than RSUs in the cortex. Depending on the stimulus conditions, two to three times more TCUs than RSUs were excited by two or more whiskers. 5. Following displacement of an adjacent whisker, unit discharges to subsequent deflections of the maximally excitatory whisker were reduced in a time-dependent fashion. The time course of response suppression was similar in TCUs and RSUs, but inhibitory interactions between adjacent whiskers were observed much less often in the thalamus. A cyclic pattern of stimulus-evoked excitation/inhibition characterizes responses in the cortical barrels but is considerably less pronounced in the thalamic barreloids. 6. The presence and/or degree of response suppression depended on which adjacent whisker was stimulated and on the angular direction of that whisker's movement. For individual TCUs, some adjacent whiskers evoked inhibition, others did not. The vast majority of RSUs displayed response suppression to all adjacent whiskers. Unlike receptive fields of TCUs, those of RSUs have small--i.e., single whisker--excitatory centers with potent and symmetrical inhibitory surrounds. 7. Fast-spike units in the barrels displayed the greatest spontaneous and stimulus evoked activities and were the least selective for whisker movements at different angular directions. FSUs had the largest excitatory receptive fields; 100% responded to two or more vibrissae.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2918358 TI - Mnemonic coding of visual space in the monkey's dorsolateral prefrontal cortex. AB - 1. An oculomotor delayed-response task was used to examine the spatial memory functions of neurons in primate prefrontal cortex. Monkeys were trained to fixate a central spot during a brief presentation (0.5 s) of a peripheral cue and throughout a subsequent delay period (1-6 s), and then, upon the extinction of the fixation target, to make a saccadic eye movement to where the cue had been presented. Cues were usually presented in one of eight different locations separated by 45 degrees. This task thus requires monkeys to direct their gaze to the location of a remembered visual cue, controls the retinal coordinates of the visual cues, controls the monkey's oculomotor behavior during the delay period, and also allows precise measurement of the timing and direction of the relevant behavioral responses. 2. Recordings were obtained from 288 neurons in the prefrontal cortex within and surrounding the principal sulcus (PS) while monkeys performed this task. An additional 31 neurons in the frontal eye fields (FEF) region within and near the anterior bank of the arcuate sulcus were also studied. 3. Of the 288 PS neurons, 170 exhibited task-related activity during at least one phase of this task and, of these, 87 showed significant excitation or inhibition of activity during the delay period relative to activity during the intertrial interval. 4. Delay period activity was classified as directional for 79% of these 87 neurons in that significant responses only occurred following cues located over a certain range of visual field directions and were weak or absent for other cue directions. The remaining 21% were omnidirectional, i.e., showed comparable delay period activity for all visual field locations tested. Directional preferences, or lack thereof, were maintained across different delay intervals (1 6 s). 5. For 50 of the 87 PS neurons, activity during the delay period was significantly elevated above the neuron's spontaneous rate for at least one cue location; for the remaining 37 neurons only inhibitory delay period activity was seen. Nearly all (92%) neurons with excitatory delay period activity were directional and few (8%) were omnidirectional. Most (62%) neurons with purely inhibitory delay period activity were directional, but a substantial minority (38%) was omnidirectional. 6. Fifteen of the neurons with excitatory directional delay period activity also had significant inhibitory delay period activity for other cue directions. These inhibitory responses were usually strongest for, or centered about, cue directions roughly opposite those optimal for excitatory responses.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2918359 TI - Input-output relationships of the primary face motor cortex in the monkey (Macaca fascicularis). AB - 1. Somatosensory afferent input and its relationship with efferent output were examined in the primary face motor cortex (MI) and adjacent cerebral cortical areas. Excitatory afferent inputs were tested in a total of 1,654 single neurons recorded in awake or anesthetized monkeys (Macaca fascicularis), and output was characterized in these same monkeys by the movement and EMG responses evoked by intracortical microstimulation (ICMS) at the neuronal recording sites. 2. Most neurons in the MI area responded to light tactile stimulation of the orofacial region, especially the upper lip, lower lip, and tongue. Although contralateral afferent inputs predominated, 21% of the neurons received ipsilateral or bilateral orofacial inputs. The afferent input evoked by tactile stimulation of the upper and lower lips was represented especially at the medial border and the input from the tongue at the lateral border of MI. However, in most regions of MI between the medial and lateral borders, an intermingling of tactile inputs from different orofacial areas occurred. Multiple representation of tactile input from the same orofacial area was found in several, often quite separate, intracortical sites in MI. 3. Only a small proportion of the MI neurons could be activated by the deep stimuli used (e.g., stretch and pressure applied to muscle, passive jaw movement, low-intensity stimulation of hypoglossal nerve) from the orofacial region. Those neurons which did respond to these low-threshold deep inputs were not clearly segregated from those which responded to tactile input, although most of the neurons receiving deep input were located in the rostral part of MI. 4. A somatotopic pattern of representation of orofacial tactile input was more obvious in the primary face somatosensory cortex (SI). At the medial border of SI, the periorbital area was represented, then followed laterally in sequence the tactile representation of the upper lip, lower lip, and intraoral area. Contralateral afferent inputs predominated, but as in MI, a considerable proportion of SI neurons received ipsilateral or bilateral orofacial inputs. Few neurons in the region explored (areas 3b, 1, and 2) responded to deep orofacial stimuli. 5. Tactile input also dominated the input patterns of neurons in the premotor cortex (PM). Most neurons received ipsilateral or bilateral orofacial afferent inputs and no clear somatotopic pattern was noted. Several PM neurons were also activated by visual stimuli. 6. Muscle twitches evoked by ICMS were limited to MI.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2918360 TI - Effects of baclofen on transient neurons in the mudpuppy retina: electrogenic and network actions. AB - 1. Baclofen increases transient light responses of amacrine and ganglion cells despite acting as a classical inhibitory transmitter to both hyperpolarize and shunt these cells. 2. This effect seems to occur at the level of the inner retina and appears not to be due to an additional input from bipolar cells. 3. In some transient cells baclofen increases the total amplitude of the light response but does not change the peak potential of the light evoked EPSP. In these cells, the baclofen-induced enhancement can be accounted for by an increase in driving force of the excitatory postsynaptic potential (EPSP) resulting from the hyperpolarization. 4. However, in other cells the peak of the light response after baclofen application is greater, which cannot be accounted for by a change in driving force. This effect of baclofen can be mimicked by a blockers of gamma aminobutyric acid (GABA) and glycine, suggesting that in these cells baclofen's enhancement is due in part to network effects resulting in a removal of sustained inhibition. 5. Therefore, the paradoxical effect of an inhibitory transmitter producing an enhancement of synaptic responses seems due to at least two mechanisms. 6. The results indicate that some transient cells receive significant tonic inhibition which limits their response amplitude in a push-pull type mechanism, but other cells are not under this inhibitory control process. PMID- 2918361 TI - Encoding of electrical, thermal, and mechanical noxious stimuli by subnucleus reticularis dorsalis neurons in the rat medulla. AB - 1. In anesthetized rats, recordings were made within the medullary subnucleus reticularis dorsalis (SRD) from neurons that exhibited convergence of nociceptive inputs from the entire body. Neurons with total nociceptive convergence (TNC) responded to suprathreshold percutaneous electrical stimuli (2-ms duration) with an early and a late peak due to activation of A delta- and C-fibers, respectively, no matter which part of the body was stimulated. Neurons with partial nociceptive convergence (PNC) responded to the same stimuli with an A delta-peak regardless of which part of the body was stimulated and with a C-peak of activation from some, mainly contralateral, parts of the body. The characteristics of the responses of these neurons to the application of graded intensities of electrical, thermal, and mechanical stimuli were analyzed. 2. All TNC neurons and 85% of PNC neurons responded to A delta- and C-fiber activation following percutaneous electrical stimulation of the contralateral hindpaw. With regard to A delta-fiber-evoked responses, a linear relationship between the logarithm of the applied current and the magnitude of the responses was found within the 0.25- to 6.0-mA and 0.5- to 24-mA ranges for TNC and PNC neurons, respectively; however, these curves were essentially similar. With regard to C fiber-evoked responses, such a linear relationship was found within the 1.5- to 6.0-mA range for both types of SRD neurons, although the TNC neurons presented larger C-fiber-evoked responses than did the PNC neurons. 3. TNC and PNC neurons linearly increased their discharges during the application of noxious thermal stimuli to the contralateral hindpaw within the range 44-52 degrees C; the mean responses evoked by noxious heat from TNC neurons were of higher magnitude than those from PNC neurons. The majority of SRD neurons presented long-lasting afterdischarges, especially with the highest temperature employed (52 degrees C). 4. TNC neurons monotonically increased their discharges during graded mechanical or thermal stimulation of the tail. When mechanical stimuli were applied, a linear relationship was found between the logarithm of the strength of the mechanical stimulus and the neuronal discharges, in the 5.3- to 7.4-N/cm2 range. With thermal stimulation, TNC neurons linearly increased their discharges in the 44-52 degrees C range. When increasing amounts of the tail were immersed in a 50 degrees C waterbath, TNC neurons increased their discharges within a restricted range of tail surface areas (0.9-5.7 cm2); further increases in the stimulated surface size were not followed by increases in firing rate.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2918362 TI - Variance analysis of excitatory postsynaptic potentials in cat spinal motoneurons during posttetanic potentiation. AB - 1. Fluctuations in the peak amplitudes of composite excitatory postsynaptic potentials (EPSPs) in cat spinal motoneurons were analyzed during posttetanic potentiation (PTP). Each of a series of identical tetanic stimulus trains delivered to a muscle nerve was followed by 45 test stimuli applied at 2-s intervals. The mean peak amplitude and mean peak variance were calculated for EPSPs evoked by all those stimuli following a tetanus with the same time interval. It was assumed that the variance arises primarily from the probabilistic all-or-none behavior of single synaptic boutons and background noise due to spontaneous synaptic activity and thermal noise in the recording system. The variance was corrected for the contribution from additive Gaussian background noise. 2. If it is assumed that individual synaptic boutons behave independently, corrected mean peak variance and mean peak amplitude are related by a parabolic function. The expected parabolic relationship was seen in 9 of 31 cases studied, and the parameters of the best parabolic fit to the data allowed estimation of some synaptic properties. From these parameters, the mean amplitude of the unit EPSP (v) was estimated to be 102.1 +/- 57.4 (SD) microV. An average of 3.7 boutons comprised each Ia-motoneuron contact system. 3. On average, only 27% of all synaptic boutons given off by the stimulated Ia fibers to one motoneuron were active and releasing transmitter during unpotentiated reflex transmission. The remaining 73% of the synapse population was intermittently silent. The population of boutons which took part in synaptic transmission could be divided into two subpopulations, one with a release probability P = 1 and a second with a mean release probability P = 0.13 +/- 0.086. 4. We conclude that synaptic boutons connecting Ia afferents to motoneurons exist in two populations, one having a high and one a low probability of transmitter release. Transmitter release is quantal, resulting in a unit EPSP of approximately 100 microV measured at the motoneuron soma. PMID- 2918363 TI - Evidence that repetitive seizures in the hippocampus cause a lasting reduction of GABAergic inhibition. AB - 1. A method was developed to quantify paired-pulse depression of population spikes in the CA1 region of the hippocampus of urethane-anesthetized rats with paired stimuli to the contralateral CA3 region at various states of excitability of pyramidal cells. This method was applied to measure changes following recurrent seizures, a single seizure, or long-term potentiation (LTP). 2. In naive animals paired-pulse depression was highly variable at low stimulus intensities, but constant above a certain "threshold" stimulus intensity. The potency of paired-pulse depression also depended on the time between paired stimuli, being maximal at an interpulse interval of 20 ms. The general relationships of paired-pulse depression to stimulus intensity and to interpulse interval were unaltered after LTP, after a single seizure, and after recurrent seizures, but there were quantitative changes in the last two cases. 3. A variety of pharmacologic agents known to interact with GABAergic inhibition were studied for their effect on paired-pulse depression. These agents affected earlier phases of paired-pulse depression (interpulse intervals less than or equal to 100 ms). The GABA agonist muscimol and the benzodiazepine diazepam enhanced paired-pulse depression whereas the GABA antagonist bicuculline decreased it. 4. Repeated seizures elicited by trains (50-Hz, 10-s durations every 5 min) of electrical stimuli to the hippocampus were associated with progressive lengthening of afterdischarges. 5. Recurrent seizures caused a statistically significant reduction in the potency of earlier phases of paired-pulse depression. There was an increase in the potency of later phases of paired-pulse depression after recurrent seizures, but this was not statistically significant. These changes were present for at least 2 h after the last seizure. 6. An antidromic-orthdromic paired-pulse protocol was used to exclude slow conductance changes as the cause of paired-pulse depression. Paired-pulse depression measured with this method was also decreased by recurrent seizures. 7. A single seizure caused a small reduction in paired-pulse depression that dissipated in less than an hour. 8. A single seizure caused LTP of stimulus intensity versus population spike curves whereas recurrent seizures attenuated or even reversed the potentiation, leading to a rightward shift of the curves relative to control curves. When LTP was produced by a less intense stimulus train (50-Hz, 400-ms duration), there were no associated seizures nor was there any change in paired-pulse depression.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2918364 TI - Loss of inhibition precedes delayed spontaneous seizures in the hippocampus after tetanic electrical stimulation. AB - 1. The electrophysiological consequences of a "continuous" hippocampal stimulation protocol consisting of 10-s-long stimulus trains administered every 11 s for 90 min to the hippocampus of urethane-anesthetized rats were studied. During the period of stimulation, there was an initial phase with tonic discharges occurring every 1-2 min followed by a secondary phase in which there were well-demarcated recurrent clonic seizures. 2. At the end of the 90 min stimulation period, 7 out of a total of 14 animals studied show epileptiform activity that lasted one-half hour. The other half show disappearance of epileptiform activity within 2 min after terminating the stimulus. In all the animals a quiescent period then followed. In 11 of the animals studied, spontaneous seizures reappeared after the quiescent period had been present for several hours. 3. A paired-pulse method that in previous studies had been shown to reflect the functional state of GABAergic inhibition was employed. Paired pulse depression in the CA1 region of the hippocampus was measured before administration of stimulus trains, in the quiescent period following the trains, and during and after spontaneous seizures. By comparing indices of maximal inhibition under the various experimental conditions, estimates of the relative amount of inhibition lost could be made. 4. All animals showed reduction of paired-pulse depression in the quiescent period following stimulation when compared with prestimulation values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918365 TI - Depth distribution of neuronal activity related to a visual reaction time task in the monkey prefrontal cortex. AB - 1. The depth distributions of neurons with changes in activity during a visual reaction time task were investigated in the dorsolateral prefrontal cortex of the macaque monkey, using glass micropipettes. The task was initiated by the monkey pressing a lever and consisted of an initial waiting phase (3.0-s period); a warning phase (green lamp, a variable period of 1.5-3.5 s); a lever-release GO phase (red lamp); and a final reward phase. The locations of neurons, in terms of the cortical layer, whose activities were recorded during performance of the task, were estimated histologically by marks made during the recording session. Marks were made by passing a DC current (anodal, 10-20 microA, 10-20 s) through the tip of an electrode which contained carbon fibers. Manipulator readings during the experiments and measurements of the distance of the marks from the cortical surface for 28 electrode penetrations showed a discrepancy of 2.0 +/- 5.0%, indicating that the depths at which task-related neurons were located could be estimated with errors of less than 10%. 2. Out of 162 task-related neurons recorded during 31 electrode penetrations, 53 showed changes in activity only during the warning phase (W-type; 19 phasic, 10 phasic-tonic, and 24 tonic), 37 showed changes only during the GO phase (GO-type; 4 Cue-coupled, 27 Intermediate, and 6 Movement-coupled), 34 showed changes during both the warning and GO phases (WG-type; 9 phasic, 10 phasic-tonic, and 15 tonic), and 38 showed changes during the reward phase (RE-type; 22 phasic and 16 tonic). 3. The various task-related neurons were distributed differently in different layers. Most neurons were recorded from layers III through V. In layer I, no neurons were recorded. In layer II, only a small number of neurons, with changes during the warning phase, were recorded (n = 7, 4%). One-third of the neurons were recorded in layer III (n = 51, 32%); neurons with changes during the warning phase were the most numerous (n = 24) and were significantly more numerous than neurons with changes associated with other phases of the task. One-fourth of the neurons were recorded in layer IV (n = 43, 27%); neurons with changes during the reward phase were the most numerous (n = 19), and were significantly more numerous than neurons with changes during both the warning and GO phases and also more numerous than neurons with changes during the GO phase.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2918366 TI - Components of the responses of a population of DSCT neurons determined from single-unit recordings. AB - 1. Impulse activity of single units belonging to the dorsal spinocerebella tract (DSCT) was recorded in response to electrical stimulation of peripheral muscle nerves at group I intensities. The responses for 187 units were determined using a spike train analysis technique that facilitates the comparison of poststimulus response time course across units (response probability function, RPF; 16). 2. The poststimulus changes in impulse activity were represented in the waveform of the RPF. Principal component analysis was used to determine the component waveforms that were common to the responses across units. The analysis showed that there were a few waveforms that dominated the majority of the responses (85% of the total variability was accounted for by five principal component waveforms). 3. A cluster analysis based on three principal component waveforms revealed seven major groups of responses according to the patterns of their poststimulus activity. These response types were composed of different combinations of short- or long-latency excitation and inhibition. The same clusters were formed regardless of response amplitude or the source of the stimulus. 4. The responses were characterized by three general features, revealed by the first three principal components. The primary feature was the sign of the response, either mostly excitatory or inhibitory. The second feature was a distinction between a short- (up to 15 ms) and long- (approximately 30 ms) latency to peak response, and the third feature was the appearance of two separate phases of opposite sign in some of the responses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918367 TI - Components of responses of a population of DSCT neurons to muscle stretch and contraction. AB - 1. Impulse activity of 264 units of the dorsal spinocerebellar tract (DSCT) was recorded during random contraction or stretch in hindlimb muscles. Contractions were evoked in either the isolated gastrocnemius-soleus (GS) muscles or the intact limb during crossed-extensor reflexes; stretches were applied to the isolated GS. 2. The time course of poststimulus changes in spike activity of DSCT neurons was determined from the response probability function (RPF; Ref. 15). These data were analyzed using principal component and cluster analysis to group the responses according to the RPF waveforms. 3. The responses to each type of stimulus displayed a remarkable similarity in time course, regardless of the type of stimulus used. The responses were also similar to those observed previously during single shock nerve stimulation (14). 4. The most reasonable explanation for these results is that the time course of excitability changes in DSCT neurons is determined less by particular types of receptors or patterns of afferent fiber activity than by the circuitry and afferent pathways impinging on the neurons of the DSCT. 5. The functional organization of DSCT suggested by these results includes a wide divergence from sensory receptors along polysynaptic pathways to DSCT neurons and considerable convergence onto each neuron from a diversity of receptors. Individual DSCT cells may respond to stimuli with one of a few stereo typical response patterns yet the distribution of those patterns among the units of the DSCT population may be unique for each stimulus. PMID- 2918368 TI - The two major phosphoproteins in growth cones are probably identical to two protein kinase C substrates correlated with persistence of long-term potentiation. AB - Regulation of neural protein kinase C (PKC) activity appears to directly affect the persistence of long-term potentiation (LTP; Akers and Routtenberg, 1985; Lovinger et al., 1985, 1986, 1987; Routtenberg et al., 1985, 1986; Akers et al., 1986; Linden et al., 1987), a model of neural plasticity (Bliss and Lomo, 1973). In addition, the in vitro phosphorylation of a brain-specific PKC substrate, protein F1 (Mr 47 kDa, pl 4.5), has been directly correlated with persistence of LTP (Lovinger et al., 1986). Because PKC has been implicated in neurite outgrowth and is present at high levels in growth cone-rich areas of fetal brain, we investigated and characterized PKC substrates in a preparation of isolated nerve growth cone fragments from fetal rat brain and compared them with PKC substrates found in adult rat hippocampus. Four major proteins in the growth cone preparation showed endogenous phosphorylation levels at least 10-fold greater than any other phosphoproteins. Three of these 4 phosphoproteins, termed pp40, pp46, and pp80 (Katz et al., 1985), were phosphorylated by exogenous PKC in a dose-dependent manner, indicating that PKC activity might be of particular importance relative to other kinases in growth cone function. The 2 most highly labeled PKC substrates, pp46 and pp80, comigrated on 2-dimensional gels with the adult hippocampal proteins F1 and "80k" (Mr 78-80 kDa, pl 4.0), respectively. In addition, similarities in charge heterogeneity, 2-dimensional phosphopeptide maps, and increased phosphorylation in the presence of exogenous PKC or PKC stimulators suggest that protein F1 and 80k are highly homologous to, if not identical to, pp46 and pp80, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918369 TI - Passive membrane properties of motorneurons and their role in long-distance signaling in the nematode Ascaris. AB - In the motornervous system of the large parasitic nematode, Ascaris suum, the dorsal and ventral nerve cords are connected by a repeating pattern of single identified motorneuron processes, called commissures (Stretton et al., 1978). By making microelectrode penetrations of the commissures, we here report the first successful intracellular recordings of nematode neurons. These cells, like muscle cells of Ascaris, exhibit resting potentials of approximately -30 to -40 mV. Several tests indicate that these are the normal resting potentials of the cells and are not low due to damage. Using 2 intracellular microelectrodes (one for stimulation and one for recording), we have determined the input resistance and cable properties of commissural motorneurons. Over the physiological voltage range, the steady-state I-V plots are linear with little indication that voltage sensitive conductances are contributing substantially to signaling. The membrane capacitance is comparable to that of single biological membranes (range, 0.4-0.9 microF/cm2) and the internal resistivity (range, 79-314 omega cm) is similar to that found in other cells. Because of unusually large membrane resistances (range, 61-251 k omega cm2), the space constants, lambda, are high (range, 4-10 mm). Such membrane properties produce cells that are well-designed for conducting passive signals over long distances. This long-distance signaling ability appears to be due to the intrinsic properties of the motorneuron membrane itself. PMID- 2918370 TI - Kinesthetic and visual control of a bimanual task: specification of direction and amplitude. AB - Kinesthetic information about a perturbation can quickly modify motor activity by producing reflexive compensation. The purpose of the present study was to determine how quickly kinesthetic information about target movement can modify motor activity. Visual information about target movement is known to guide motor activity both quickly and accurately. Therefore, we compared the speed and accuracy of responses to kinesthetically and visually presented targets. Human subjects produced changes in elbow torque as quickly and accurately as possible after the random presentation of 1 of 8 target torques. Information about the direction and amplitude of the target torque was provided either kinesthetically or visually. Responses to kinesthetic targets started at an average latency of 150 msec, and after an additional 159 msec, these responses became accurately graded according to target amplitude. Responses to visual targets started at an average latency of 250 msec, and after an additional 208 msec, these responses became accurately graded according to target amplitude. The accuracy of responses to kinesthetic targets was very similar to the accuracy of responses to visual targets. We conclude that the neural processing of kinesthetic information about target movement is sufficiently fast and accurate to guide typical motor activities. PMID- 2918371 TI - Association of neurotensin binding sites with sensory and visceromotor components of the vagus nerve. AB - Specific neurotensin (NT) binding sites were recently shown to be highly concentrated in the nucleus of the solitary tract (NTS), which receives primary vagal afferents, and in the dorsal motor nucleus of the vagus (DMN), which contains the cell bodies of origin of vagal preganglionic neurons. To investigate the relationship of these binding sites with sensory and visceromotor components of the vagus nerve, they were labeled here in vitro, using monoiodo[Tyr3]neurotensin (125I-NT) and visualized by light microscopic radioautography in the dorsomedial medulla of both intact and unilaterally vagotomized rats, in the nodose ganglia of intact animals, and in ligated vagus nerves. Unilateral vagotomy performed above the nodose ganglion resulted in a significant ipsilateral decrease in 125I-NT binding within both the NTS and the DMN, suggesting that NT binding sites were associated with both primary afferent fibers and preganglionic nerve cell bodies. The selective radioautographic labeling of a subpopulation (approximately 15%) of neuronal perikarya in the nodose ganglion confirmed that a proportion of vagal afferent neurons contained NT binding sites. Following vagus nerve ligation, a pile up of radiolabeled NT binding sites was observed on both sides of the nerve crush, indicating that NT receptor components were transported both anterogradely and retrogradely along fibers of the vagus nerve. We conclude that NT receptors are synthesized and transported within a subpopulation of afferent and efferent components of the vagus nerve and that NT may therefore act presynaptically upon vagal axon terminals in both central and peripheral nervous systems. PMID- 2918372 TI - Inhibitors of protein kinase C prevent enhancement of calcium current and action potentials in peptidergic neurons of Aplysia. AB - Following brief stimulation of an afferent pathway, the bag cell neurons of Aplysia undergo a dramatic change in excitability, resulting in a prolonged discharge of spontaneous action potentials. During the discharge, the action potentials of the bag cell neurons become enhanced in height and width. The afterdischarge triggers release of neuroactive peptides that initiate egg-laying behavior in this animal. Evidence suggests that changes in excitability of the bag cell neurons may be mediated by activation of protein kinase C (PKC) and cAMP dependent protein kinase (cAMP-PK). PKC activators, such as the phorbol ester TPA (12-O-tetradecanoyl-13-phorbol acetate), enhance the amplitude of action potentials in isolated bag cell neurons in cell culture. These agents act by unmasking a previously covert species of voltage-dependent calcium channel resulting in an increase in calcium current. In the accompanying paper (Conn et al., 1989), we showed that H-7, a protein kinase inhibitor, inhibits the effect of TPA, and is a selective inhibitor of PKC relative to cAMP-PK in these cells. We now report that another PKC inhibitor, sphinganine, also inhibits the effect of TPA on action potential height and calcium current in cultured bag cell neurons, and that N-acetylsphinganine, an inactive sphinganine analog, fails to inhibit the effects of PKC activators. Although both H-7 and sphinganine prevent the effects of TPA when added prior to TPA addition, neither compound reverses the effects of TPA when added after the action potentials have already become enhanced by TPA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918373 TI - Interruptions of fictive scratch motor rhythms by activation of cutaneous flexion reflex afferents in the turtle. AB - A low-spinal immobilized turtle displays a fictive scratch reflex in hindlimb muscle nerves in response to mechanical stimulation of specific regions of the shell (Robertson et al., 1985). There are 3 forms of the scratch reflex: the rostral, the pocket, and the caudal; each exhibits rhythmic activation of hindlimb motor neurons. Cutaneous stimulation of the distal hindlimb elicits a fictive flexion reflex that exhibits tonic excitation of hip protractor (flexor) motor neurons and tonic inhibition of knee extensor motor neurons (Stein et al., 1982). In the present study, we describe the motor pattern blends that resulted from transient activation of either the ipsilateral or the contralateral flexion reflex pathway during ongoing scratch motor patterns. Two types of blends were observed: (1) insertions of a flexion reflex synergy into an interrupted scratch cycle and (2) deletions of parts of a scratch cycle. Associated with each type of motor pattern blend was a permanent reset of the ongoing scratch rhythm. The sign of the reset (phase-advance or phase-delay) could be predicted for all forms of the scratch based on the location of the foot stimulus (ipsi- or contralateral) and its timing relative to the hip protractor/retractor cycle. The timing of knee extensor activity within the hip cycle is different for each form of the scratch (Robertson et al., 1985); thus, the sign of the reset cannot be predicted from the timing of the stimulus relative to the knee extensor cycle. These results indicate the importance of the hip rhythm in determining the overall timing of the scratch reflex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918374 TI - Two sexually dimorphic cell groups in the human brain. AB - A quantitative analysis of the volume of 4 cell groups in the preoptic-anterior hypothalamic area (PO-AHA) and of the supraoptic nucleus (SON) of the human brain was performed in 22 age-matched male and female individuals. We suggest the term Interstitial Nuclei of the Anterior Hypothalamus (INAH 1-4) to identify these 4 previously undescribed cell groups in the PO-AHA. While 2 INAH and the SON were not sexually dimorphic, gender-related differences were found in the other 2 cell groups. One nucleus (INAH-3) was 2.8 times larger in the male brain than in the female brain irrespective of age. The other cell group (INAH-2) was twice as large in the male brain, but also appeared to be related in women to circulating steroid hormone levels. Since the PO-AHA influences gonadotropin secretion, maternal behavior, and sexual behavior in several mammalian species, these results suggest that functional sex differences in the hypothalamus may be related to sex differences in neural structure. PMID- 2918375 TI - Peripheral target choice by homologous neurons during embryogenesis of the medicinal leech. I. Segment-specific preferences of Retzius cells. AB - A pair of large serotonergic neurons, the Retzius (Rz) cells, is found in each segment of the leech nervous system. Most Rz cells innervate the body wall of their own segment as well as adjacent anterior and posterior segments. Rz cells in segments 5 and 6 [Rz (5,6)] instead innervate the reproductive tissue found only in those segments. Rz cells from adjacent segments [Rz (4,7)] provide the serotonergic innervation of the body wall of segments 5 and 6. During embryogenesis, the body wall and the reproductive tissue are apparently available to both Rz (5,6) and Rz (4,7), yet these neurons choose different targets. We asked how Rz (5,6) and Rz (4,7) choose their respective peripheral targets in the reproductive segments by ablating either the reproductive tissue or specific Rz cells. Ablation of the reproductive tissue caused Rz (5,6) to innervate body wall, although not as proficiently as did standard Rz cells, suggesting a preference of Rz (5,6) for reproductive tissue. Ablation of those Rz cells that would normally innervate the body wall of segments 5 and 6 did not cause Rz (5,6) to innervate body wall, ruling out competition for this target. When Rz (5,6) were ablated, Rz (4,7) innervated the body wall of segments 5 and 6 normally and did not innervate reproductive tissue. Thus, competition did not act in the choice of target by Rz (4,7) either. These results suggest that during normal development, Rz (5,6) and Rz (4,7) choose their targets independently of one another rather than competing for the available targets and that these cells have segment-specific target preferences. PMID- 2918376 TI - Peripheral target choice by homologous neurons during embryogenesis of the medicinal leech. II. Innervation of ectopic reproductive tissue by nonreproductive Retzius cells. AB - Most Retzius (Rz) cells innervate the body wall of their own and adjacent segments, whereas Rz cells in segments 5 and 6 [Rz (5,6)] innervate the reproductive tissue, which is found only in those segments. Results from the preceding paper (Loer and Kristan, 1989a) showed that Rz (5,6) and standard Rz cells do not normally compete for their respective peripheral targets. These experiments did not, however, distinguish between 2 other possible mechanisms of target selection: intrinsic differences in target preference or differences in the timing of target contact. In order to separate these possibilities experimentally, we transplanted reproductive primordia to standard segments. We found that standard Rz cells were capable of densely innervating ectopic reproductive tissue, provided the target was transplanted at an appropriate time and location. Furthermore, after some processes of standard Rz cells contacted ectopic reproductive tissue, the rest of the cell's processes showed their growth in a way reminiscent of Rz (5,6) processes. These results strongly suggest that Rz (5,6) innervate reproductive tissue at least partly because their processes contact this target during a period that is optimal for them to associate with the target, or when the reproductive tissue is most attractive to Rz processes, or both. PMID- 2918377 TI - Visual-visual associative learning and reward-association learning in monkeys: the role of the amygdala. AB - Three Cynomolgus monkeys (Macaca fascicularis) took part in an experiment on visual learning set in an automatic apparatus. Each new visual discrimination problem was solved using a visual secondary reinforcer consisting of a white line. If the monkey chose the correct stimulus (by touching it), the white line appeared over the correct stimulus. Primary food reward was delivered only after a new problem was solved to a criterion, and the problem was then replaced by a new one. Thus, within-problem learning did not rely on primary reinforcement but on the visual secondary reinforcer. The animals were trained preoperatively in visual learning set with this procedure and were assessed postoperatively for their ability to learn new visual discriminations with the same procedure. Bilateral amygdalectomy did not significantly impair the animals' learning ability in this task. Learning remained unimpaired when transection of the uncinate fascicle and of the fornix was added to amygdalectomy. The effect of bilateral amygdalectomy in this task was much less severe than in a similar task we previously studied, with auditory secondary reinforcers. The results show that the involvement of the amygdala in processes of secondary reinforcement depends on the sensory properties of the secondary reinforcer. From these and other recent results, we conclude that the sensory attributes of a reinforcer are easily associated with a discriminative stimulus when they are in the same modality and same spatial location as the discriminative stimulus and that this sensory-sensory association is independent of the amygdala. PMID- 2918378 TI - Relationship between phosphorylation and synthesis of goldfish optic nerve proteins during regeneration. AB - After intraocular injection of radiolabeled phosphate and 3H-proline, the labeling of goldfish optic nerve proteins was monitored over a 7 week period of regeneration following a lesion to the optic tract. Labeled phosphate incorporation into total nerve protein increased to a peak value about twice that in normal nerve at 3 weeks after injury, then declined to slightly above normal by 7 weeks. Incorporation of 3H-proline showed a higher rise and a steeper decline, with values still significantly above normal at 7 weeks. Two-dimensional gel electrophoresis revealed that almost all the individual proteins examined underwent an increase in 3H-proline incorporation with a peak at about 3 weeks. However, only 4 proteins showed an increase in incorporation of 32P correlated with the increase in 3H-proline. The closest correlation was seen for protein 4, the equivalent of the growth-associated protein GAP-43; for the other 3 proteins (15, 31, and 38) 32P incorporation remained elevated even when 3H-proline incorporation had declined. Two other proteins (24e and 48) showed increased 32P incorporation not correlated with 3H-proline changes. Several proteins showed a decrease in 32P incorporation, even though 3H-proline incorporation was increased. For example, the phosphorylation of ON2, a neuronal intermediate filament protein, showed a long-lasting decline, which was already evident at 1 week and had not yet returned to normal by 7 weeks. Other proteins in this group (33, 37, and 46) showed a faster recovery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918379 TI - Sprouts emerging from the dendrites of axotomized lamprey central neurons have axonlike ultrastructure. AB - We have examined the dendritic and axonal ultrastructure of intact anterior bulbar reticulospinal neurons (ABCs) in the CNS of the larval sea lamprey and compared it with that of the dendrites and neuritic sprouts from ABCs examined 2 months following axotomy. Dendrites and axons of intact ABCs are distinguishable from one another by several ultrastructural criteria: (1) the predominance of microtubules in the dendritic cytoskeleton and neurofilaments in that of the axon, (2) the exclusively postsynaptic status of the dendrites versus the presynaptic status of the axon, and (3) the presence of polyribosomes and large numbers of mitochondria in the dendrites and their respective absence and scarcity in the axon. The ultrastructure of axonal sprouts evoked by axotomy of ABCs 1-1.5 mm from their somata ("intermediate axotomy") in many ways resembled that of intact axons. Axonal sprouts were presynaptic to other neurons, and their cytoskeletons consisted mainly of neurofilaments. They also exhibited some features not seen in either axons or dendrites, such as numerous clusters of small vesicles that were not associated with synapses and, in some cases, close associations with glial elements. We also examined sprouts emerging from the dendrites of ABCs following axotomy within 500 microns of their somata ("close axotomy") and found that such "dendritic" sprouts closely resembled axonal sprouts; they possessed neurofilament-dominated cytoskeletons, were presynaptic to other neurons, and were often associated with glial elements. The dendrites of ABCs undergoing dendritic sprouting retained their normal gross morphology but possessed a mixture of "axonal" and "dendritic" ultrastructural characteristics, exhibiting neurofilament-dominated cytoskeletons while remaining entirely postsynaptic to other neurons. However, there were significantly fewer synapses on the dendrites of axotomized cells than were found on the dendrites of intact ABCs. We conclude that sprouts evoked by axotomy are intrinsically axonal in character whether they originate from the axon stump or from the dendritic tree. Our results also suggest that the materials necessary for axonal regeneration may displace elements of the dendritic cytoskeleton as they are transported through the dendrites to the emerging "dendritic" sprouts following close axotomy. PMID- 2918380 TI - Postnatal development of corticocortical efferents from area 17 in the cat's visual cortex. AB - We are interested in the postnatal development of corticocortical connections in the cat's visual cortex. In this study, we injected the anterograde tracer 3H proline into visual cortical area 17 of kittens, aged 4-70 d, and adult cats to visualize the distribution of terminals of the association projections to areas 18, 19, 21a, and the lateral suprasylvian visual cortex. The density of anterograde label was quantified using computerized image analysis. There was dense labeling at topographically appropriate locations in area 18 in animals of all ages. In 4- and 8-d-old kittens, other extrastriate areas (19, 21a and the lateral suprasylvian cortex) contained only sparse label, localized in a few solitary axons; these areas were densely labeled in animals aged 12 d or more. In kittens aged 4-20 d there was considerable, widespread label within fibers located in the white matter, and many of these axons lay underneath regions of extrastriate, and also striate, cortex that were almost certainly not destined to be persistently innervated by cells at the injection site. This pattern of extensive white matter label was not seen in animals older than 20 d. In each extrastriate region, from the earliest age at which we identified dense cortical innervation from area 17, the terminals were distributed in clusters. At first these patches were mainly in infragranular layers, but later, during the second and third postnatal weeks, they began to appear in more superficial laminae. By 70 d, an adult-like distribution of terminals was found in each extrastriate area: most fibers appeared to end in layers II and III in areas 18, 19, and 21a and centered on layer IV in the medial bank of the middle suprasylvian sulcus in adult cats. We suggest that the development of ipsilateral association projections from area 17 to extrastriate cortex is a 2-stage process. First, cells at a particular point in area 17 send immature fibers in a nonspecific fashion through white matter towards a very wide area of extrastriate cortex. Second, corticocortical axons penetrate extrastriate cortex mainly in patches at topographically appropriate regions and grow to their targets in a specific fashion. PMID- 2918381 TI - Differentiation of axon-related Schwann cells in vitro: II. Control of myelin formation by basal lamina. AB - Several recent observations suggest that Schwann cell (SC) differentiation, including myelin formation, is dependent upon the development of basal lamina which characteristically surrounds each axon-SC unit in peripheral nerve. This dependence can be tested in a neuron-SC culture system developed in our laboratory in which SC differentiation, including basal lamina formation and myelination, is faithfully reproduced. The use of serum-free, defined medium (DM) with this culture system allows axon-driven SC proliferation but not basal lamina formation or myelination. We previously demonstrated that ascorbic acid, in the presence of a nondialyzable serum factor(s), stimulates basal lamina assembly and myelin formation with similar dose-response relationships (Eldridge et al., 1987). We hypothesized that ascorbic acid acts to promote SC myelination indirectly, by enabling the assembly of basal lamina. We now provide support for this hypothesis by demonstrating the following. (1) Pepsin-resistant triple helical collagen molecules were produced only by SCs grown in the presence of ascorbic acid, suggesting that triple-helical type IV collagen may mediate the effect of ascorbic acid on basal lamina formation. (2) The formation of myelin by oligodendrocytes, which myelinate axons in the CNS without the concomitant deposition of basal lamina, was little affected by ascorbic acid, suggesting that the biosynthesis and assembly of myelin per se does not require ascorbic acid. (3) The provision of exogenous basal lamina matrix to SCs grown with neurons in DM without ascorbic acid promoted control levels of myelination (and basal lamina formation); the provision of exogenous fibrillar collagen matrix did not. (4) Purified laminin promoted control levels of myelination in the absence of ascorbic acid, but purified type IV collagen and heparan sulfate proteoglycan (HSPG) did not. Laminin caused SCs to assemble basal lamina-like structures that contained not only laminin but also HSPG and non-triple-helical type IV collagen. Thus, several types of experiments demonstrate that SC myelin formation can be controlled by regulating the ability of the SC to assemble basal lamina, illustrating that acquisition of basal lamina is a crucial prefatory step for further SC differentiation. PMID- 2918382 TI - Two distinct mechanisms, differentially affected by excitatory amino acids, trigger GABA release from fetal mouse striatal neurons in primary culture. AB - The mechanisms leading to Ca2+-dependent and Ca2+-independent GABA release were studied on highly purified striatal neurons developed in primary culture. Ca2+ dependent GABA release, which represents about 75% of the 56 mM K+ effect was totally inhibited when striatal neurons were first exposed to tetanus toxin (TnTx) (10 micrograms/ml) for 24 hr. The K+ effect was potentiated when 1 mM nipecotic acid (an inhibitor of the GABA uptake system) was added during the stimulation period or when Na+ was replaced by Li+. However, no difference in the GABA release measured under high-K+ conditions was observed after a 22 min preincubation of the neurons in a medium containing nipecotic acid or Li+. Replacement of Cl- ions by SO4(2-) did not modify K+-evoked GABA release. Ca2+ independent GABA release was stimulated by veratridine (20 microM), ouabain (3 mM), and monensin (20 microM), as well as the excitatory amino acids glutamate (100 microM), N-methyl-D-aspartate (100 microM), quisqualate (10 microM), and kainate (1 mM), drugs known to increase intracellular Na+ concentration. The veratridine- or glutamate-evoked GABA release was neither inhibited when intracellular Ca2+ content was reduced by more than 90% nor by treatment of the neurons to TnTx. However, the Ca2+-independent GABA release elicited by veratridine was inhibited by preincubation of the neurons in a medium containing 1 mM nipectotic acid and in a medium containing Li+ instead of Na+ or SO4(2-) instead of Cl-. These results strongly suggest that 2 different GABA release mechanisms exist in striatal neurons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918383 TI - The expression of the growth associated protein B50/GAP43 in the olfactory system of neonatal and adult rats. AB - B50/GAP43 is a neuron-specific phosphoprotein whose expression is associated with neural development and synaptic plasticity. Its postnatal ontogeny was investigated in the primary olfactory pathway of the rat using immunohistochemical methods. The unique ability of the olfactory neuroepithelium to generate new neurons from a population of precursor cells present in the basal cell layer of this tissue makes it a valuable model in the study of neural development. In newborn rats B50/GAP43 is present throughout the entire population of olfactory receptor neurons. These cells are stained throughout, from the ciliated dendritic knob to their axon terminals in the bulb. This appears to be the first example of unambiguous B50/GAP43 expression in dendritic processes. With increasing age the distribution of this protein becomes progressively restricted to a subpopulation of olfactory neurons. Comparison of the expression of B50/GAP43 and the olfactory marker protein (OMP), a polypeptide only present in mature olfactory neurons, revealed that during postnatal development of the olfactory system these 2 proteins are expressed in a nearly reciprocal fashion. In adult animals (3.5 months-6 months of age), B50/GAP43 positive cells are exclusively present adjacent to the basal cell layer of the neuroepithelium. Basal cells appear to be unstained. The region of the epithelium containing the B50/GAP43-positive cells is virtually devoid of OMP-positive neurons. A significant fraction of these B50/GAP43-containing cells bear dendritic and neuritic processes. However, these cells do not express olfactory cilia. It is probable that the olfactory neurons expressing the growth-associated B50/GAP43 protein may correspond to a particular subset of olfactory neurons at an intermediate state of maturation. PMID- 2918384 TI - Amacrine cell interactions underlying the response to change in the tiger salamander retina. AB - The neural circuitry and pharmacology underlying transient signal formation at the bipolar-amacrine cell interface were studied. Synaptic currents were measured with whole cell patch clamp in retinal slices. Cell types were identified with Lucifer yellow staining. Activity was initiated with puffs of kainate of known time course and spatial spread delivered at bipolar dendrites. OFF bipolar cells responded to kainate with a sustained inward current, but ON bipolar cells were silent. Two types of amacrine cell were found: (1) narrow field cells, with processes that extended laterally less than 200 microns, responding with a sustained inward current, and (2) wide field cells, with processes that extended laterally by up to 1 mm, responding with a brief transient inward current followed by a more sustained outward current. We pharmacologically dissected the synaptic interactions underlying the transient current in the wide field amacrine cell. In the presence of 5-aminovaleric acid (AVA), the time course of this transient current was increased so that it resembled the response of bipolar cells. Because AVA is a GABAB antagonist, it appears to block an opposing signal that truncates the sustained excitatory bipolar input, thereby generating the transient. GABAB specificity is confirmed by (1) block of the transient inward current by baclofen, a GABAB agonist, and (2) block of the baclofen effect by AVA. The site of GABAB action appears to be presynaptic to the amacrine cell membrane because neither baclofen nor AVA, in combination with picrotoxin, had a direct effect at the amacrine cell membrane. GABAB receptors are often found at presynaptic terminals where they modulate calcium or potassium conductances. It has been shown that bipolar cell terminals receive a GABAergic synaptic input (Vaughn et al., 1981; Wu et al., 1981; Tachibana and Kaneko, 1987). The narrow field sustained-responding amacrine cells appear to be GABAergic (Werblin et al., 1988). This suggests that transient activity measured in wide field amacrine cells is formed at a population of bipolar cell terminals by GABAergic feedback from narrow field amacrine cells at GABAB receptors. PMID- 2918385 TI - Androgen-specific critical periods for the organization of the major pelvic ganglion. AB - Previous studies indicate that the major pelvic ganglion (PG) is dependent on testosterone for normal development. Tyrosine hydroxylase (T-OH), DOPA decarboxylase, and choline acetyltransferase (CAT) activities are significantly reduced by postnatal castration on day 10-11, while testosterone replacement therapy reversed all developmental enzyme activity deficits (Melvin and Hamill, 1987). In the present studies castration on the day of birth combined with various testosterone-replacement paradigms produced effects demonstrating that the PG is sensitive to testosterone dosage and time of administration during early postnatal development. Gonadal hormone replacement experiments show that the androgens testosterone and dihydrotestosterone were effective in restoring T OH and CAT activity deficits produced by neonatal castration. Estrogen therapy reversed the deficits in CAT activity, but was ineffective in reversing the alterations in T-OH activity. Treatment of pregnant dams with the anti-androgen flutamide altered the ontogeny of T-OH and CAT activities in pups despite replacement therapy on the day of birth. Thus, androgen-critical periods exist prenatally as well as postnatally. These studies suggest that the organization of PG development is critically dependent on both the time of exposure and dose of testosterone. Prenatal and postnatal critical periods appear to exist. In addition, the lack of an effect of estradiol on tyrosine hydroxylase activity suggests that androgens are specifically responsible for organizing the noradrenergic development of the PG. PMID- 2918386 TI - Lack of specificity of polyunsaturated fats in the inhibition of rat liver glucose-6-phosphate dehydrogenase. AB - The mechanism of the effect of polyunsaturated fatty acids (PUFA) on glucose-6 phosphate dehydrogenase (EC 1.1.1.49) (G6PDH) was studied in young, male Wistar rats. Starvation-refeeding increased G6PDH level above that seen in ad libitum fed animals (enzyme overshoot). A second episode of starvation-refeeding produced even higher levels of G6PDH activity (induction increment). Interposing a high fat diet (containing PUFA) between starvation and feeding the inducer diet abolished one-half to two-thirds of the overshoot. Feeding a high fat diet between the two starvations abolished the induction increment. Inhibitors of arachidonic acid metabolism were not able to reverse the PUFA effect. In another set of experiments it was shown that both linoleic and linolenic acid are equally effective in either reducing the overshoot or abolishing the induction increment. The evidence was interpreted as supporting a hypothesis that the PUFA effect does not require the formation of a specific end product of arachidonic metabolism in a direct way. PMID- 2918387 TI - Plasma ammonia, plasma, brain and liver amino acids and urea cycle enzyme activities in rats fed ammonium acetate. AB - Male Sprague-Dawley rats were trained to eat a 6% casein diet within a 3-h period each day. They were then fed a 6% casein diet for 10-16 d before they were fed either the same 6% casein diet or the 6% casein diet supplemented with 15% ammonium acetate for 1 or 7 d. During the absorptive period, plasma ammonia, plasma amino acids and brain amino acids were measured on d 1 and d 7 after feeding ammonium acetate. Food intake of rats fed 15% ammonium acetate was depressed on d 1 and increased to approximately 75% of the intake of the 6% casein-fed group by d 7. On d 1 plasma ammonia of the rats fed 5% ammonium acetate was 101 microM as compared to 56 microM for the rats fed 6% casein (P less than 0.05). On d 7, plasma ammonia of the rats fed 15% ammonium acetate was 240 microM (P less than 0.05) as compared to 44 microM for the rats fed 6% casein. In rats fed 15% ammonium acetate, after 7 d ornithine transcarbamylase and arginase activities were higher and argininosuccinate synthetase activity was lower (P less than 0.05) while carbamyl phosphate synthetase activity tended to be higher than that of rats fed 6% casein. The results suggest that rats adapt to ingestion of 15% ammonium acetate by some unknown neural mechanism rather than by increases in all urea cycle enzyme activities. Feeding ammonium acetate causes changes in plasma, brain and liver amino acid concentrations. PMID- 2918388 TI - Effect of various intakes of phylloquinone on signs of vitamin K deficiency and serum and liver phylloquinone concentrations in the rat. AB - The relationship between dietary phylloquinone, serum and liver concentrations of phylloquinone, and various indices of vitamin K adequacy have been studied in male rats fed a purified diet containing various levels of phylloquinone. In excess of 500 micrograms phylloquinone/kg diet was needed to prevent the most sensitive signs of vitamin K deficiency. Liver phylloquinone concentrations were shown to be correlated with dietary phylloquinone intake. Serum phylloquinone was not correlated with either diet or liver concentration of phylloquinone and did not increase with increased dietary intake until the liver contained sufficient vitamin to maintain optimal synthesis of vitamin K-dependent proteins. Because of the rapid loss of vitamin from the liver, prior ingestion of a high level of vitamin K had little influence on liver vitamin K concentrations beyond the first 2 d of a deficient period. When rats consumed a diet containing 500 micrograms phylloquinone/kg diet in 3 h, liver and serum phylloquinone concentrations fluctuated drastically following this feeding period. During the subsequent 24-h period, liver phylloquinone concentrations decreased to a level that would not support maximal activity of the hepatic vitamin K-dependent carboxylase. PMID- 2918389 TI - Role of intestinal microflora in the metabolism of vitamin B-6 and 4' deoxypyridoxine examined using germfree guinea pigs and rats. AB - In previous work identification of urinary metabolites of 4'-deoxypyridoxine which had been oxidized in the 5'-position and long-term dilution of labeled urinary metabolites with unlabeled molecules suggested possible microbial contributions. In the current studies germfree guinea pigs were able to convert 4'-deoxypyridoxine to 4'-deoxy-5-pyridoxic acid demonstrating that the ability to oxidize the 5'-position is not restricted to microorganisms. Labelling curves for urinary pyridoxic acid in rats continuously fed [14C]pyridoxine since weaning were similar in conventional and germfree animals indicating that any vitamin B-6 synthesized in the intestinal tract was not readily absorbed and metabolized. Therefore, coprophagy did not make a detectable contribution to vitamin B-6 metabolism in rats receiving a nutritionally complete diet. The difficulty in achieving comparable labeling in adult animals is probably due to very slow turnover of portions of the vitamin B-6 pool and not to microbial production of vitamin B-6. The total pool calculated from the radioactivity in the germ-free rats averaged 16.2 +/- 0.8 nmol vitamin B-6 compounds/g body wt. Only 10% of the ingested label was recovered in the feces. In addition, only about 50% of the label excreted in the urine appeared as 4-pyridoxic acid in rats. These observations suggest that it may be difficult to quantitate the total urinary and fecal excretion of ingested vitamin B-6 without using tracers. PMID- 2918390 TI - Biosynthesis of a novel form of vitamin B-6 by tumor cells. AB - Studies on the time-course utilization of radiolabeled pyridoxine in hepatoma bearing rats led to the discovery of a novel vitamin B-6 product. It is present in a spectrum of tumor lines, but it is absent or occurs minimally in normal tissues. Hepatomas incorporate up to 20-30% of labeled pyridoxine into the novel species. Its structure was tentatively identified as adenosine-N6-methyl, propylthioether-N-pyridoximine-5'-phosphate. In the present study, 3B3 mouse human hybridoma cells were incubated with radiolabeled precursor molecules, perchloric acid cell extracts were analyzed by high performance liquid chromatography (HPLC), and radioactivity in effluent fractions was measured. The results show that [G-3H]pyridoxine, [2,8-3H]adenosine, L-[35S]cysteine and L-[U 14C]serine are incorporated into the novel tumor product. These findings are interpreted to indicate that the correct structure of the novel product is adenosine-N6-diethylthioether-N'-pyridoximine-5'-phosphate. Further, these data demonstrate that tumor cells have evolved novel enzymatic steps for metabolism of vitamin B-6. The potential use of the novel metabolite as a marker for tumor genesis and establishment is especially significant, as the compound is peculiar to the neoplastic state. PMID- 2918391 TI - Production and reversal of the neuromuscular pathology and related signs of zinc deficiency in guinea pigs. AB - The purposes of this study were to use vocalization and posture as indices of the neuromuscular pathology that develops in zinc-deficient guinea pigs and to determine the rate of depletion before and of repletion after intraperitoneal (IP) zinc therapy. When severe signs of deficiency developed, tissues were analyzed for their zinc content to assess sites of depletable and mobilizable zinc stores. Weanling guinea pigs were fed low (less than 1 mg/kg) and adequate (100 mg/kg) zinc diets based on isolated soybean protein or autoclaved egg white. The first signs (stage 1) of vocalization due to handling, abnormal posture and skin lesions developed after approximately 4 wk. Severe (stage 3) signs followed after 5-6 wk. A single IP dose of ZnSO4 (50 mumol/kg) caused remission of signs within 4-5 d following which all signs regressed to stage 3 within 7 d. Analysis of 15 tissues from severely deficient guinea pigs showed that only plasma and bone had significantly lower zinc concentrations than tissues from comparable age related controls fed a zinc-adequate diet. It seems unlikely that major soft tissues, such as muscle, brain, liver and skin, serve as mobilizable stores of zinc for other critical metabolic functions. Bone zinc is slowly mobilized but at a rate insufficient to maintain health or even life. PMID- 2918392 TI - Incorporation of iron from an oral dose into the ferritin of the duodenal mucosa and the liver of normal and iron-deficient rats. AB - To further characterize the role of ferritin in regulating iron absorption, uptake of an oral dose of 59Fe (0.2 mg Fe/kg body wt.) into duodenal and hepatic ferritin of control and iron-deficient (ID) rats was studied. Retention and uptake of 59Fe from Fe(II)-sulfate, Fe(III)-chloride, or Fe(III)-polymaltose were measured up to 28 h after dosing. Ferritin was determined by radioimmunoassay (RIA) and 59Fe ferritin-iron by gel electrophoresis. Retention and liver content of 59Fe was higher in ID rats than in controls. The mucosa of ID rats, however, retained only one third of the amount of 59Fe retained by the mucosa of controls. The mucosal and hepatic ferritin levels were lower in ID rats than in controls. The percentage of orally administered 59Fe found in the liver ferritin was therefore higher in control than in ID rats. However, when expressed as per unit of ferritin, iron uptake was eight times higher in ID rats. In contrast, mucosa ferritin of ID rats contained one-third of 59Fe per unit of ferritin than that of controls. Assuming no change in the mechanism of iron uptake into ferritin of control and ID rats, the differential uptake of oral iron into mucosa and liver ferritin indicates either a different compartmentation of the tissue ferritin or differences in the iron transport processes, but mucosal ferritin does not withdraw iron from intestinal absorption. PMID- 2918393 TI - Inhibitory effects of phytic acid and other inositol phosphates on zinc and calcium absorption in suckling rats. AB - While it is known that phytic acid, inositol hexaphosphate, has a negative effect on zinc and calcium absorption, the effects of inositol which is phosphorylated to a lesser extent are less known. We have prepared inositol triphosphate (IP-3), tetraphosphate (IP-4), pentaphosphate (IP-5) and hexaphosphate (IP-6) by hydrolysis of sodium phytate and separation by ion-exchange chromatography and have studied their effect on zinc and calcium absorption. Using a suckling rat pup model, we found that liver uptake of 65Zn after 6 h was 5% of the total dose from solutions of IP-6, 19% from IP-5, 28% from IP-4, 29% from IP-3 and 31% from ZnCl2 (control). Non-absorbed calcium was 17%, 1.4%, 0.5%, 0.5% and 0.5% of the given dose of 45Ca, respectively. Thus, at a high degree of phosphorylation (IP 6, IP-5), zinc and calcium uptake was inhibited, while no effect was observed for the other phosphates. Consequently, total "phytate" analysis, which includes inositol phosphates with varying degrees of phosphorylation, can give misleading information with regard to mineral availability. In addition, even limited dephosphorylation of inositol hexaphosphate can have a positive effect on mineral absorption. PMID- 2918394 TI - Selenium content and glutathione peroxidase activity of milk from vegetarian and nonvegetarian women. AB - The concentration of selenium (Se) in milk samples obtained from 26 lacto-ovo vegetarian (vegetarian) women was significantly greater (22.2 +/- 0.8 ng/ml) than from 12 nonvegetarian women (16.8 +/- 1.3). Mean GSH-Px activity (EC 1.11.1.9) in milk from vegetarians was 146% of that in milk from nonvegetarians. A significant correlation between GSH-Px activity and Se concentration was observed (r = 0.76). Likewise a significant correlation was observed between milk linoleic acid content and GSH-Px activity (r = 0.68). In undialyzed samples from vegetarian women, most of the increased content of Se was found in fractions containing proteins of 100 kdaltons (kD) or more. The high glutathione peroxidase activity in milk from vegetarians was associated with selenoproteins in the 90 to 100 kD range. A distinct 40 kD Se peak was also detected in milk from vegetarians. There was no difference in Se intake between the two groups of women. Therefore, although data from the present study show that both the quantity and distribution of Se in human milk can be modified by the maternal diet, the increased Se content and GSH-Px activity in milk from vegetarians cannot be explained by an increased Se intake. PMID- 2918395 TI - Effect of molybdenum supplementation on hepatic trace elements and enzymes of female rats. AB - The effects of molybdenum (Mo) supplementation in the drinking water at the levels of 0.1, 0.5, 1.0, 2.0, 5.0 and 10.0 mg/l on the hepatic trace element concentrations and enzyme activities of female Sprague-Dawley rats were studied. The mean hepatic Mo concentration increased significantly in the rats supplemented with 0.1 mg Mo/l as compared to the nonsupplemented rats, but a further significant increase did not occur until the supplementation level reached 5-10 mg Mo/l drinking water. Hepatic copper concentration of the group given 0.1 mg Mo/l and hepatic iron content of the groups given 0.1 or 0.5 mg Mo/l were significantly higher than those of the other groups. The hepatic xanthine dehydrogenase/oxidase activity was not significantly affected by Mo supplementation. The hepatic sulfite oxidase (SOX) activity of the group given 0.1 mg Mo/l was significantly higher than that of the nonsupplemented group. The SOX activities of all the other supplemented groups were at a significantly different level intermediate between the first two. The hepatic superoxide dismutase (SOD) activity was significantly higher in the group given 0.1 mg/l than in the other groups. These results indicated that molybdenum enzymes and SOD might not be participants in previously reported anticarcinogenic activity of Mo, as supplementation at the level of 0.1 mg/l had been observed to be inefficacious in inhibiting N-nitrosomethylurea-induced mammary tumor incidence. PMID- 2918396 TI - A comparison of intrinsic and extrinsic tracer methods for estimating calcium bioavailability to rats from dairy foods. AB - Dairy products doubly labeled with 45Ca and 47Ca were used to evaluate an extrinsic labeling procedure for calcium bioavailability determination. Nonfat milk, yogurt, and fresh cheese curd were prepared from caprine milk that was intrinsically labeled with 45Ca. The products were then labeled extrinsically with 47Ca and administered to rats by gavage. The 47Ca to 45Ca ratio in bone and teeth averaged about 1.00 with either milk, yogurt, or CaCl2, but the ratio was about 1.04 when dosed with cheese curd. Ca absorption, determined by whole-body counting of 47Ca, was lower (P less than 0.05) in cheese curd (59%) than in either milk (69%), yogurt (72%), or CaCl2 (72%). Expressed as percent of dose, the absorption of 47Ca was highly correlated with bone 47Ca (r = 0.973) and with bone 45Ca (r = 0.946). Correlation between tibia 47Ca and tibia 45Ca was r = 0.923. For the dairy products tested, our results indicated that extrinsic 47Ca was absorbed similarly to intrinsic 45Ca. Moreover, the percent of radioactive dose retained in bone appears to be a valid indicator of relative bioavailability of food Ca. PMID- 2918397 TI - Effects of dietary and abomasally infused choline on milk production responses of lactating dairy cows. AB - Three experiments investigated the effects of exogenous choline on milk production responses of dairy cows. Ruminally fistulated Holstein cows were fed total mixed diets containing 30% corn silage and 70% corn/soybean meal-based concentrate in experiment 1, or 40% corn silage and 60% concentrate in experiments 2 and 3. In experiment 1, the effects of unsupplemented (control), dietary supplemented choline (50 g/d) and abomasally infused choline (50 g/d) were examined using three first-lactation cows in a 3 X 3 Latin square design. While dietary added choline had no effect, abomasally infused choline increased daily milk and 4% fat-corrected milk yield 3.2 and 3.8 kg/d respectively. In experiment 2, effect of daily abomasal infusion of 0, 30, 60 and 90 g choline were studied using four mature cows in a 4 X 4 Latin square design. Fat-corrected milk and milk fat percent were 2.6 kg/d and 0.59 percentage units higher for cows infused with 30 g/d choline than for unsupplemented controls, with 60 and 90 g/d choline infusions showing smaller effects. In experiment 3, daily abomasal infusion of 0 or 40 g choline were studied using four mature cows in a switchback design. Choline infusion (40 g/d) increased daily milk 1.6 kg/d over control while having no effect on milk composition or feed intake. Results of these experiments suggest a possible requirement for supplementing choline in lactating dairy cows. PMID- 2918399 TI - Fractional contributions to total carnitine in the neonatal rat. AB - This study was designed to determine the fraction of tissue total carnitine derived from the mother in utero, from milk, and from fetal and neonatal de novo synthesis. Female rats were offered drinking water ad libitum containing either tritium or [14C]-labeled carnitine (0.1 mCi/mmol, 5 mM). The rats were mated, and after birth, the pups of females given the tritium-labeled water were switched with the pups of rats given the [14C]-labeled carnitine (cross-fostering). Analyses of neonatal tissue total carnitine in five tissues were determined on d 0, 1, 2, 5, 10, and 20 after birth. Carnitine derived from neonatal de novo synthesis remained relatively constant from birth throughout the 20 d period, ranging from 26% in liver to 50% in the heart at d 0. The contribution from milk carnitine rose rapidly after birth until d 5, at which time it became relatively constant, ranging from 40.8% in heart to 55.4% in kidney at d 20. The fetus is a major contributor to its own tissue carnitine. Nevertheless, the infant rat is dependent upon external sources of carnitine in order to maintain tissue carnitine levels. PMID- 2918398 TI - Species and strain differences in teratogenic effects of biotin deficiency in rodents. AB - The teratogenicity of maternal biotin deficiency of mice, rats and Syrian hamsters was compared. Biotin deficiency during pregnancy caused severe malformations and growth retardation in mouse fetuses. The malformations were mainly cleft palate, micrognathia, micromelia and open eyelid. The ICR and C57BL strains of mice were more susceptible than the A/Jax strain to biotin deficiency. In rats, no malformations were seen in the fetuses from biotin-deficient dams. In hamsters, embryonic lethality was very high in biotin-deficient dams, and teratogenicity of biotin deficiency was rather equivocal. The results of measurements of the maternal and fetal biotin content suggest that a possible underlying mechanism is a difference in the efficiency of the mother-to-fetus transport of biotin among these species. PMID- 2918400 TI - Phosphoenolpyruvate carboxykinase of rat small intestine: distribution and regulation of activity and mRNA levels. AB - Phosphoenolpyruvate carboxykinase (PEPCK) activity is present along the length of rat small intestine and in enterocytes throughout the villus-crypt axis. There is no detectable activity in submucosal layers. Messenger RNA encoding PEPCK is detectable in rat intestinal mucosa and the relative abundance increases markedly (3- to 8-fold) during starvation or streptozotocin-diabetes. However, these changes are not matched by changes in enzyme activity which are only slightly increased (1.5-fold). The intestine of neonatal rats possesses relatively high amounts of both PEPCK activity and mRNA. Based on the distribution and regulation of intestinal PEPCK, it is proposed that the enzyme does not play a significant role in either gluconeogenesis or glutamine catabolism in adult rats. PMID- 2918401 TI - Biosynthesis of hippurate, urea and pyrimidines in the fatty liver: studies with rats fed orotic acid or a diet deficient in choline and inositol, and with genetically obese (Zucker) rats. AB - The activities of pathways for the biosynthesis of hippurate, urea and pyrimidines in hepatocytes isolated from lean livers were compared with those from three sources of fatty liver: a) the genetically obese Zucker rat, b) Sprague-Dawley rats fed a diet deficient in choline and inositol, and c) Sprague Dawley rats fed a diet supplemented with orotic acid. The capacity for hippurate synthesis was not significantly affected by fat accumulation, but ureagenesis from saturating ammonia and ornithine was diminished about 50% in all models when fat content rose above 12% wet wt of liver. Pyrimidine biosynthesis under these conditions was similarly diminished with fat accumulation. Ureagenesis was inhibited by sodium benzoate in hepatocytes from lean livers, but not in hepatocytes from fatty livers. Other results suggest that higher rates of ureagenesis than could be achieved with the fatty liver are required in order to demonstrate inhibition by benzoate. Incorporation of [14C]NaHCO3 into orotate was also inhibited by sodium benzoate, but in hepatocytes from fatty as well as lean livers. The metabolic basis for impairment of ureagenesis and pyrimidine biosynthesis in the fatty liver requires further study. That the capacity for hippurate synthesis was not significantly affected suggests a pathway-specific mechanism. PMID- 2918402 TI - Short term neonatal starvation altered cholera toxin binding in rabbits. AB - Acute neonatal malnutrition alters lumenal glycoproteins as demonstrated by altered lectin binding. To determine the effect of a 72-h fast on lumenal glycolipids, specifically the monosialoganglioside GM1, we quantitated cholera toxin (CT) binding and adenylate cyclase activity. The calculated number of specific sites for CT binding to microvillus membrane (MVM) from newborn rabbits fasted for 72 h was decreased in MVM from proximal small bowel (7 +/- 0.8 x 10(8)/micrograms protein) compared to 72-h control neonatal rabbits (18 +/- 3.3 x 10(8) micrograms protein). In distal small bowel there was no difference in the calculated receptor sites/micrograms MVM protein between fasted (8 +/- 1.7 x 10(8)) and fed (11 +/- 4 x 10(8)) groups. MVM prepared from proximal small bowel of fed animals bound significantly more CT than MVM prepared from distal small bowel of fed animals. The affinity for CT was the same in all MVM preparations. Neuraminidase treatment of MVM resulted in increased CT binding in fed and fasted rabbit proximal and distal MVM preparations, but the greatest increase occurred in MVM prepared from proximal small bowel from fasted animals. There was no difference in adenylate cyclase activity in fed, fasted, and proximal or distal small bowel crude membrane preparations. Refeeding (120 h) resulted in normalization of CT binding in MVM from proximal small bowel of fasted animals. We conclude a 72-h fast in neonatal rabbits resulted in decreased regional CT binding in MVM prepared from proximal small bowel of fasted animals, but no change in adenylate cyclase activity. Refeeding reverses CT binding abnormalities. PMID- 2918403 TI - Hormonal and nutritional regulation of phosphoenolpyruvate carboxykinase mRNA levels in chicken kidney. AB - In chickens, the kidney possesses a distinct cytosolic phosphoenolpyruvate carboxykinase activity which is not found in the liver. This activity is subject to long-term regulation by diet and changes in acid-base status. The activity is increased during starvation or metabolic acidosis. In addition, an unidentified component of some standard chicken diets results in altered activity. Using a specific cDNA probe the abundance of PEPCK mRNA has been determined in chicken kidney in vivo and in vitro. The abundance of PEPCK mRNA in chicken kidney increases during starvation and is rapidly decreased after refeeding carbohydrate. In isolated kidney tubules the abundance of the mRNA is increased after incubation with glucocorticoids, dibutyryl cAMP or hormones acting via changes in the concentration of cAMP (parathyroid hormone, epinephrine). Phorbol esters or hormones acting via calcium-dependent mechanisms were without effect. The results support the hypothesis that in the chicken the kidney is the major site of gluconeogenesis from substrates other than lactate and thus plays an important role in the maintenance of glucose homeostasis. PMID- 2918404 TI - The future direction of nutrition research: unraveling the diet-disease connection. PMID- 2918405 TI - The future direction of nutrition research: strong inference. PMID- 2918406 TI - Comparison of participants and nonparticipants in a work site cancer awareness and screening program. AB - In 1985, Pennzoil Company offered a company-paid cancer awareness and screening program focusing on breast and colorectal cancers for its employees. Following a lecture/slide presentation, employees filled out a risk assessment questionnaire. Those at risk for breast and/or colorectal cancers were invited for consultation, mammography, and/or short colonoscopy. Overall completion rates were 49% for mammography, 20% for the fecal occult blood test, and 31% for short colon oscopy, but these rates varied by risk status. Moreover, the same demographic and risk factors were not consistently associated with completion of the same screening procedure across risk groups. Based on these findings, we suggest that different interventions may need to be developed depending on the risk characteristics of subgroups within the target population. PMID- 2918407 TI - Pulmonary alveolar proteinosis and cement dust: a case report. AB - Pulmonary alveolar proteinosis developed in a 29-year-old white man within 2 years of working as a cement truck driver. Pulmonary alveolar proteinosis (PAP), an uncommon respiratory disorder characterized by the accumulation of phospholipid material within the alveoli, has been described in association with exposure to silica, aluminum oxide, and a variety of dusts and fumes. Although a link between exposure to Portland cement and PAP has not been previously noted, this type of cement contains nearly 20% silica. Lung biopsy material, originally used to diagnose PAP, was reviewed under electron dispersive spectroscopy. Analysis indicated the presence of silica particles within the alveolar fluid and macrophages. A number of items support a causal relationship between exposure to cement dust and PAP: (1) the temporal sequence between assuming job duties and the development of the illness, (2) improvement following removal from further exposure, (3) dusty, unprotected working conditions, (4) the presence of silica within the cement, and (5) the alveolar fluid from periodic acid-Schiff-positive lung tissue. PMID- 2918408 TI - Liver injury tests in hazardous waste workers: the role of obesity. AB - The prevalence of fatty liver disease at autopsy ranges from 40% to 80% in Europe and North America, and liver injury tests are abnormal in up to 8% of healthy populations. Liver injury tests were therefore examined in a group of 325 workers without exposure to hepatotoxins to identify the influence of obesity and gender. Obesity was a strong predictor of the degree of abnormality for serum levels of arginine and alanine aminotransferase and of alkaline phosphatase, even in the normal range. Women generally demonstrated lower levels of these enzymes. Workers with morbid obesity were substantially more likely to have abnormal liver injury tests. Obesity and gender must be considered in the interpretation of abnormal liver injury tests in hazardous waste workers. PMID- 2918409 TI - Education in management aspects of occupational and environmental health and safety programs. PMID- 2918410 TI - Clinical ecology in the workplace. AB - The field of clinical ecology is based on a putative diagnosis of "environmental illness," applied to persons who have multiple symptoms and are believed to be sensitive to numerous items in the environment. Increasingly this diagnosis is being used by workers for an occupational disability claim. Medical records of 90 workers claiming work-related "environmental illness" were reviewed. The majority were women. They worked in a variety of occupations with no unifying feature of the type of work or the claimed causative exposure. Symptoms were multiple and unaccompanied by objective clinical findings. Careful review of medical records showed that most had their symptoms before the claimed occupational exposure. Examining physicians who were not clinical ecologists invariably arrived at other diagnoses, usually psychiatric. This retrospective review lends no support to the clinical ecology concept of "environmental illness." PMID- 2918411 TI - The relationship between retrospective health insurance claims and a health risk appraisal-generated measure of health status. AB - This research examined the relationship between a measure of health status (defined as the health index--the difference between actual and appraised ages) derived from a health risk appraisal and retrospective health insurance claims taken from one cooperating work organization. A model was defined consisting of 3 year retrospective medical claims as the criterion and age and the health index as predictors. Using a cube-root transformation of medical claims, a significant inverse relationship for age and the health index was identified for men. No relationships were found for women. It was concluded that, for men when age is held constant, a negative relationship exists between retrospective medical claims and a health risk appraisal-generated health status indicator, the health index. PMID- 2918412 TI - Mortality among nonwhite men in the meat industry. AB - Mortality among 5145 nonwhite men in a local meatcutters' union in Baltimore who were observed between July 1949 and December 1980, was compared with that of nonwhite men of the United States general population, through the estimation of standardized mortality ratios. The study population had potential for exposure to viruses that cause leukemia and lymphoma in cattle and chickens, and other harmful agents. Statistically significant standardized mortality ratios of 2.1 for lung cancer and 3.1 for cancer of the esophagus were observed among workers in abattoirs and meatpacking plants, respectively. The results obtained are consistent with findings for white male and female members of the same union, and with other published data. PMID- 2918413 TI - A follow-up study of workers at a dye and resin manufacturing plant. AB - A total of 2642 men employed at a dye and resin manufacturing plant in New Jersey were observed from the opening of the plant in 1952 through 1985, and their mortality rates were compared with the rates of United States white men. The workers' mortality experience was related to former employment at the Cincinnati Chemical Works, which had produced or used benzidine and beta-naphthylamine. The 2553 men who had never worked at the Cincinnati Chemical Works had fewer than expected deaths from all causes combined (317 observed/402 expected) and equal numbers of observed and expected cancer deaths (89/89). The 89 former Cincinnati Chemical Works employees had an excess of cancer (17/8.6, P = .02), which was due to increased mortality from bladder (3/0.25, P = .004), kidney (2/0.21, P = .04), and CNS (2/0.22, P = .04) cancer. There also were several increases in cancers among men employed in certain work areas at the New Jersey plant. These included elevated mortality from lung (18/9.2, P = .01) and liver (3/0.46, P = .02) cancer among maintenance workers, from stomach (3/0.40, P = .02) and CNS (3/0.44, P = .02) cancer among azo dye workers, and from lung cancer (4/0.91, P = .03) among epichlorohydrin workers. The lung cancer excess among maintenance workers increased with length of employment, suggesting an association with an unidentified occupational exposure. Other associations were based on small numbers of deaths, and their interpretation is not clear. PMID- 2918414 TI - Career options of occupational physicians. PMID- 2918415 TI - Reproductive hazards of semiconductor industry. PMID- 2918416 TI - The mechanical and morphological properties of bone beneath internal fixation plates of differing rigidity. AB - The internal fixation of diaphyseal fractures by bone plates is a well recognized treatment. The normal physiological stress of bone is reduced by plates that cause a negative balance of bone-remodeling processes. Many investigators have shown that the degree of stress protection is dependent on the rigidity of the plates. It was the aim of this study to quantify mechanical and morphological changes at different locations in a plated diaphyseal bone as a function of differing plate rigidity. Two types of plates with the same size but different materials were used. The stainless steel plates had a modulus of elasticity and bending stiffness 3.2 times higher than the carbon fiber reinforced carbon plates. Both types of plates were applied to the intact right and left femora of six foxhounds for 6 months. The stiffer stainless steel plates led to a significantly higher bone loss and correspondingly greater loss of mechanical properties. These effects were greatest directly beneath the plate and less with increasing distance from the plate. PMID- 2918417 TI - The effect of radiation on the fracture repair process. A biomechanical evaluation of a closed fracture in a rat model. AB - The effects of a single dose of irradiation on the biomechanical parameters of the fracture healing process were studied in a rat model. Intramedullary pinning was performed before production of a closed femoral midshaft fracture. The experimental group was exposed to 900 rad 3 days after fracture and was compared with a control group with a similar fracture that received no irradiation. Animals were killed at intervals ranging from 2-16 weeks after surgery and the bones were tested until failure in torsion. In the irradiated groups, a delay of 4 weeks was noted in the biomechanical parameters associated with fracture healing (torque to failure, torsional stiffness, angle to failure, and biomechanical stage). Despite this delay in the normal temporal progression, the staging and stiffness approached normal controls within an 8-week period. However, the torque to failure remained below normal levels at the conclusion of this study. These results differ from a previous study using an open fracture model. PMID- 2918418 TI - Limb lengthening by epiphyseal distraction in chondrodystrophic bone: an experimental study in the canine femur. AB - Epiphyseal distraction of the left distal femur was accomplished in 18 chondrodystrophic dogs (age 19-22 weeks). A distraction rate of 0.5 mm/day was applied by means of a unilateral device. Epiphysiolysis occurred after 4 to 9 days. Lengthening was continued for 3 weeks. The animals were killed at 3 (Group 1; n = 5), 19 (Group 2; n = 10), and 71 (Group 3; n = 3) weeks after the end of distraction to verify the magnitude of elongation at removal of the device (Group 1) and at the time of growth cessation (Groups 2 and 3), and to register possible permanent secondary joint changes (Group 3). The average lengthening of 1.2 cm (12.3%) at removal of the device was reduced to 0.7 cm (6.4%) at cessation of growth. The middiaphyseal diameter of the elongated femur was enlarged after the lengthening procedure in all animals. The average torsional strength of the elongated femur compared with the contralateral control was 83% in Group 1, 98% in Group 2, and 107% in Group 3. Degenerative changes were observed in the knee joints of three animals in each group. A two-way analysis of variance was applied for all data sets to test differences between control and elongated bones and between time periods. The reduction in gained length by retardation of residual growth in the distal femur was significant (p less than 0.05). The difference in external diameter between lengthened and control bones was significant in Groups 1 and 3 (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918419 TI - Low body weight as a risk factor for hip fracture in both black and white women. AB - A lower incidence of hip fracture in black women has been reported by several studies. The most frequently proposed explanations for this phenomenon have included a genetically greater bone mass, better preservation of bone due to the fact that certain populations of black women perform more physical labor, and the impact of other unidentified environmental and/or lifestyle factors. This retrospective study demonstrates that low body weight is as significant a risk factor for hip fracture in black women as it is in white women. Coupled with the known higher prevalence of obesity in the older black female population, the findings of this study suggest that differences in body weight may be a significant and possibly sufficient explanation for the lower incidence of hip fracture in black women. PMID- 2918420 TI - Growth hormone stimulates insulin-like growth factor I actions on adult articular chondrocytes. AB - We report effects of adding insulin-like growth factor I (IGF-I) and methionyl human growth hormone (GH), alone or in combination, to adult bovine articular chondrocytes plated at high density. Purified human and synthetic IGF-I stimulated chondrocyte DNA and proteoglycan synthesis. GH had no effect on either process. However, GH added in combination with IGF-I increased proteoglycan, cell associated proteoglycan, and keratan sulfate synthesis over levels observed with IGF-I alone. IGF-I and GH did not alter the hydrodynamic size of proteoglycans or synthesis of collagen. Our results show that GH and IGF-I act together to stimulate adult chondrocyte extracellular matrix synthesis. PMID- 2918421 TI - The repair of experimentally produced defects in rabbit articular cartilage by autologous chondrocyte transplantation. AB - Using the knee joints of New Zealand White rabbits, a baseline study was made to determine the intrinsic capability of cartilage for healing defects that do not fracture the subchondral plate. A second experiment examined the effect of autologous chondrocytes grown in vitro on the healing rate of these defects. To determine whether any of the reconstituted cartilage resulted from the chondrocyte graft, a third experiment was conducted involving grafts with chondrocytes that had been labeled prior to grafting with a nuclear tracer. Results were evaluated using both qualitative and quantitative light microscopy. Macroscopic results from grafted specimens displayed a marked decrease in synovitis and other degenerative changes. In defects that had received transplants, a significant amount of cartilage was reconstituted (82%) compared to ungrafted controls (18%). Autoradiography on reconstituted cartilage showed that there were labeled cells incorporated into the repair matrix. PMID- 2918422 TI - Early histologic, metabolic, and vascular assessment of anterior cruciate ligament autografts. AB - A rabbit model for anterior cruciate ligament (ACL) reconstruction using autogenous patellar tendon was utilized to study the early events of autograft cellular dynamics. Biochemical, autoradiographic, histological, and vascular injection techniques demonstrated that the native autograft cell population rapidly necroses. This repopulation occurs without a vascular contribution; cells entering the autograft are reliant upon synovial fluid nutrition. PMID- 2918423 TI - Microscopical investigation of canine anterior cruciate ligament and patellar tendon: collagen fascicle morphology and architecture. AB - The collagen structure of the canine anterior cruciate ligament (ACL) and patellar tendon (PT) was examined by using light and scanning electron microscopy. The collagen waviness known as a crimping was found to occur in ACL and PT fascicles. This waviness, seen at the periphery of fascicles, is very smooth, and its amplitude seems to decrease from the periphery toward the fascicular center. It appears as a periodic collapse of the fascicle in two dimensions. Two models of the architectural patterns of the ACL and PT wavy fascicles are presented. The constituent collagen fibrils are either parallel or twisted relative to the fascicle axis, giving rise to planar and helical wave patterns, respectively. There is a distinct difference between the ACL and PT collagen structure. The helical wave pattern occurs in both PT and ACL while the planar waveform is found only in the centrally located ACL fascicles. In addition, there is less variability in fascicular size and density over the PT cross-section than in ACL. PMID- 2918424 TI - An ultrastructural study of slipped capital femoral epiphysis: pathogenetic considerations. AB - Two normal proximal femoral growth plates and core biopsies from six patients with slipped capital femoral epiphysis (SCFE) were studied by electron microscopy. In these SCFE patients, chondrocytes from all the zones of the plate were frequently smaller than normal, more irregular in shape, and many of them were degenerating, with formation of matrix vesicles and cellular debris. Floccular electron-dense material, most likely abnormal proteoglycan, was present in the hypertrophic rough-surfaced endoplasmic reticulum and Golgi apparatus as well as in the extracellular matrix, intermingled with collagen fibrils thinner than normal and loosely arranged. Mineralization of the abnormal matrix of the longitudinal septa of the degenerating zone was either scanty or absent, with scanty formation of irregular and thin bone trabeculae. The abnormalities observed in SCFE seem to be caused by a change in chondrocyte metabolism with consequent altered synthesis and/or extracellular aggregation of both collagen and proteoglycan, and scanty mineralization of the abnormal cartilage matrix. PMID- 2918425 TI - The influence of chair height on lower limb mechanics during rising. AB - The mechanics of the lower limb were analyzed in young, adult normal subjects when rising from a seated position. Limb mechanics were described in terms of flexion-extension motion and moments at the hip, knee and ankle while rising from four seat heights corresponding to 65, 80, 100, and 115% of the subject's knee joint height. The results indicate that the maximum moment tending to flex the hip joint was higher than that occurring at the knee or ankle. The magnitude of the maximum flexion moment at the hip was not substantially influenced by chair height, changing by less than 12% between the highest and lowest chair heights. Conversely, the maximum knee flexion moments were found to be highly dependent on chair height and nearly doubled from the highest to the lowest position. The magnitude of the moments at the ankle did not change with chair height and were significantly lower than the magnitude of the moments found during normal walking. The magnitude of motion and moments at the hip were greater during chair rising than during stair-climbing or walking. The range of motion required at the knee for the lower chair heights was also greater than was reported during stair climbing studies. Thus, the combination of moments in joint angles during chair rising are unique among common activities of daily living and should be considered in chair selection as well as in the guidelines for prosthetic devices. PMID- 2918426 TI - Contact pressures in the patellofemoral joint during impact loading on the human flexed knee. AB - Currently, a bone fracture criterion is used by the automotive industry to assess the potential for a lower extremity injury from impact directed on the flexed knee. However, recent studies with animal models indicate irreversible damage to articular cartilage due to overpressures generated within the patellofemoral (P F) joint without bone fracture, and suggest this injury may lead to a progressive, degenerative disease of the joint. The purpose of this investigation was to measure contact pressure in the human P-F joint during impact loading on the isolated, flexed knee. Loads were delivered on the patella with a free-flight inertial mass that had a rigid or foam padded interface. The experiments were conducted by serially increasing the impactor velocity in repeated tests until bone fracture was observed. The distribution of maximum pressures generated within the joint was recorded with a pressure-sensitive film. Fracture of the patella or the femur occurred at impact loads of approximately 8.5 kN. The average P-F pressure was approximately 25 MPa for 8 kN of impact load on the 90 degrees flexed joint. The P-F contact area varied with the level of contact load and degree of joint flexion. The distribution of P-F pressures was nonuniform. At approximately 70% of the fracture load for the 90 degrees flexed knee, nearly 35% of the contact area was exposed to pressures greater than 25 MPa. In an earlier study by others using subchondral bone-cartilage preparations, this level of pressure resulted in fissures and lacerations of the cartilage. PMID- 2918427 TI - The effect of medial meniscectomy and coronal plane angulation on in vitro load transmission in the canine stifle joint. AB - The purpose of this study was to determine the in vitro load transmission characteristics of the canine stifle joint, paying particular attention to the positioning effect of the meniscus in the coronal plane. The intact joint was first loaded, and then tested under two different loading conditions after a complete medial meniscectomy. The first set of test conditions attempted to simulate those used by previous investigators, by ignoring the spacer effect of the meniscus and not repositioning the joint after its removal. The second set of tests was carried out after the joint was repositioned in the coronal plane to allow initial contact to occur in both tibiofemoral compartments. It is presumed that this occurs subsequent to a meniscectomy in vivo, following the application of any weight-bearing load. As with previous investigators, it was found that after meniscectomy the joints produced slightly larger displacements and lower stiffnesses than when intact (no significant differences from intact). However, repositioning the meniscectomized joint produced markedly smaller displacements (35-49%, p less than 0.01) and greater stiffnesses (47-123%, p less than 0.05) over the range of forces analyzed, compared with the intact joint. The ratio of dissipated to input energy was 42% for the intact joint, and rose following meniscectomy to 54% (p less than 0.05) with repositioning and 55% (p less than 0.05) without repositioning. Measured contact area decreased by 17% (p less than 0.05) following meniscectomy alone, and by 12% (p less than 0.05) following meniscectomy with repositioning. Since repositioning of the joint subsequent to meniscectomy (accounting for the loss of the meniscal spacer) resulted in an increase in structural stiffness, it was concluded that the medial meniscus decreases the structural stiffness of the intact stifle joint. In addition, the meniscus has a role in elastic energy storage and increasing contact area. This study is intended to serve as a baseline comparison for future in vivo studies on meniscectomy, meniscal repair, and meniscal replacement, in addition to more fully elucidating the mechanism of load transmission. A model is presented to explain both the decrease in stiffness after meniscectomy without repositioning and the increase in stiffness after meniscectomy with repositioning, employing linear springs of unequal length and different stiffnesses. After removal of the softer meniscal element and allowing joint approximation to occur, loading of the stiffer articular element results in an initially stiffer preparation. PMID- 2918428 TI - Frequency spectrum analysis of wrist motion for activities of daily living. AB - A frequency spectral analysis was performed on wrist motion data for 24 activities of daily living (ADLs). Wrist motion was measured using a triaxial electrogoniometer attached to the wrist using tape (for 12 subjects) and pins (for one subject). Results show that the average predominant frequency component of these ADLs was approximately 1 Hz with 75% of the spectral energy less than 5 Hz. The taped-on electrogoniometer, when compared with the pinned electrogoniometer, was adequate for calculating the predominant frequency component and spread of spectral data, but overestimated the magnitudes of the maximum spectral density and total area of the spectral curves. This discrepancy was largest for axial rotation. PMID- 2918429 TI - Effects of concurrent infections on growth, development, distribution, and infectivity of adult Philophthalmus megalurus and Philophthalmus gralli. AB - Chickens were infected concurrently with 10 and 20 metacercariae/eye of Philophthalmus megalurus and Philophthalmus gralli. After 14 and 34 days of growth, the adults were removed and worm lengths, return rates, stage of development, and distribution within the host recorded. In a second experiment, chickens infected on day 1 with 10 metacercariae/eye of P. megalurus were concurrently infected with a similar dose of P. gralli on day 14. At day 34, the worms were removed and evaluated for the same parameters as in the first study. The effect of concurrent infections on worm length of P. gralli but not P. megalurus was significant when compared to single species control groups. In all cases recovery rates of P. megalurus in concurrent infections were significantly lower than controls, whereas P. gralli adults were recovered at lower rates only in 20-metacercariae--14-day infections. Maturation of eggs was delayed in both species in concurrent infections at the higher infection levels. Normal distribution was disrupted more for P. gralli at the higher infection levels and longer growth periods. Philophthalmus megalurus adults rarely left their normal habitat in the conjunctival sac. A delayed infective dose of P. gralli affected both species by disrupting normal distribution patterns, delaying egg development, and, in the case of P. megalurus, reducing the recovery rate. The possible role of crowding and antagonistic effects is discussed. PMID- 2918430 TI - New feather mite species of Aralichus (Acarina, Pterolichidae) from the white capped parrot, Pionus senilis (Spix). AB - Two new feather mite species of Aralichus Gaud (Pterolichoidea, Pterolichidae) are described from the white-capped parrot Pionus senilis (Spix): Aralichus elongatus and Aralichus menchacai. Immature instars and host-parasite associations are discussed. PMID- 2918431 TI - Hemocyte population changes during the immune response of Aedes aegypti to inoculated microfilariae of Dirofilaria immitis. AB - Ultrastructural and lectin-binding studies have established that the melanotic encapsulation reaction of Aedes aegypti Liverpool strain against inoculated Dirofilaria immitis microfilariae (mff) is a hemocyte-mediated reaction. Total hemocyte counts from mff-inoculated (= immune-activated), saline-inoculated, and uninoculated female A. aegypti were determined using a hemocoel perfusion technique. Total hemocyte populations in uninoculated mosquitoes were significantly larger in younger mosquitoes, but no significant change was noted as mosquitoes aged beyond 14 days. Hemocyte populations in immune-activated mosquitoes increased from 1 to 3 days postinoculation (PI) and decreased on days 4 and 5 PI. Hemocyte populations at 1 to 4 days PI were significantly elevated in mff-inoculated A. aegypti as compared with saline-inoculated controls. Saline inoculated mosquitoes displayed little change in total hemocyte numbers from 1 to 5 days PI, and their hemocyte populations were similar to those seen in uninoculated insects of the same age. Experiments involving the inoculation of [3H]thymidine along with mff or saline alone and studies involving the administration of colchicine suggest that increased hemocyte populations in immune-activated A. aegypti are a result of mitotic division of circulating blood cells. PMID- 2918432 TI - Effects of rat and human intestinal lamina propria cells on viability and muscle establishment of Trichinella spiralis newborn larvae. AB - Although eosinophils and other inflammatory cells from the circulation and peritoneal cavity can damage Trichinella spiralis newborn larvae (NBL) in vitro, the cytotoxic potential of cells from the intestinal lamina propria, a site that may be the first line of defense against NBL migration, is unknown. Accordingly, we examined the interaction between NBL and isolated intestinal lamina propria cells (ILPC), including an enriched eosinophil population, from rats and humans. Rat ILPC killed NBL in vitro only after a prolonged incubation of 6 days. However they strongly adhered to NBL after only 4 hr incubation and prevented muscle establishment of NBL injected intravenously. Human ILPC showed similar adherence as rat ILPC but no killing was seen at the incubation time tested (36 hr). PMID- 2918433 TI - Eosinophil activation in acute and chronic chagasic myocardial lesions and deposition of toxic eosinophil granule proteins on heart myofibers. AB - Cardiac lesions in patients with Chagas' disease are infiltrated with various types of inflammatory cells, including eosinophils (EOS). We determined the proportions of resting and activated EOS in 2 types of chagasic myocardial lesions to establish whether their presence correlated with lesion severity. One lesion type was defined by interstitial infiltration associated with degeneration and necrosis of myocardial fibers; the other type presented mild myocarditis but myofibers were preserved. In all cases (1 patient with acute and 5 patients with chronic Chagas' disease), a marked degree of EOS infiltration was seen in the necrotic areas after staining either with Giemsa or immunohistochemically, using antibodies specific for the EOS cationic protein or the major basic protein of the granule. In contrast, a very small number of EOS was present in areas of the very same tissue sections displaying mild myocarditis and preserved myofibers. Of the EOS present in the necrotic areas, 42-78% were in the activated secretory stage as evidenced immunohistochemically after incubation with a monoclonal antibody specific for an epitope of the secretory but not the storage form of the EOS cationic protein. In areas with mild myocarditis this proportion was much smaller, ranging from 9 to 28%. In all cases, both the total level of resting and activated EOS in the necrotic areas correlated well with the overall degree of severity of myocarditis evaluated histopathologically. Deposits of the major basic cationic proteins of the EOS granules were found on myofibers in the necrotic areas from the acute and chronic cases, indicating EOS degranulation. PMID- 2918435 TI - Bronchoalveolar eosinophilia in guinea pigs harboring inapparent infections of Paraspidodera uncinata. AB - During the course of experiments examining the changes in cell populations in bronchoalveolar lavage (BAL) fluid in 3-11-wk-old guinea pigs, a marked increase in the numbers of eosinophils was observed in BAL fluid in untreated control animals from historical levels (observations made over the previous 2 yr) of 8.8 +/- 1.5% to levels greater than 16% and up to 44%. Repeated occurrence of this phenomenon in several different groups of guinea pigs that appeared clinically normal and the impact on our experimental studies led us to attempt to identify the cause of increased inflammatory cell numbers in these guinea pigs. Examination in 2 groups of animals of whole blood and lung tissue for the presence of bacteria or fungi revealed minor bacterial infections in one group but not the other, whereas both exhibited elevated eosinophil numbers. At necropsy, 41.7% and 60% of the animals in the 2 groups harbored the nematode Paraspidodera uncinata. Guinea pigs exhibiting eosinophil numbers in BAL fluid comparable to our historical levels were then inoculated with approximately 100 embryonated eggs of P. uncinata and developed elevated eosinophilia in BAL fluid compared to sham-inoculated animals (significant at 2 of the 3 examination times postinoculation). These findings suggest that P. uncinata is capable of causing changes in inflammatory cell populations in the lungs of guinea pigs and illustrate the importance of subclinical or inapparent infections in experimental design and interpretation. PMID- 2918434 TI - An in vitro radiolabel uptake viability assay for Onchocerca microfilariae. AB - A radiolabel uptake viability assay for Onchocerca cervicalis using [3H]2-deoxy-D glucose in Hanks' balanced salt solution, pH 7.5, at 30 C is described and compared to the traditional visual motility assay. A correlation of r = 0.92 between the assays was found, with the radiolabel uptake method apparently a more sensitive indicator of microfilarial viability. PMID- 2918436 TI - Novel C-banding patterns in Paragonimus ohirai (Trematoda: Platyhelminthes). AB - The C-banding pattern for the karyotype of Paragonimus ohirai representing individuals in a new population is reported. The short arm of chromosome 4 consisted of a large pericentromeric proximal C-band block and euchromatic tip. This pattern has not been observed previously and is designated as type E. Other new observations were: chromosome 5 was composed of pericentromeric heterochromatin, a lightly stained intercalary band at the middle portion of the short arm, and a lightly stained interstitial band at the terminal region of the long arm. Chromosome 7 consisted of pericentromeric heterochromatin and a lightly stained telomeric band at the short arm. PMID- 2918437 TI - Hymenolepis diminuta utilizes the envelope surrounding Moniliformis moniliformis in order to survive in the cockroach host. AB - The acanthocephalan Moniliformis moniliformis is surrounded by a membranous envelope that protects the parasite from hemocytic attack in the cockroach host. If injected into a cockroach infected with M. moniliformis, hatched oncospheres of the tapeworm Hymenolepis diminuta are able to penetrate this envelope and, once inside, utilize its protective function in order to develop. These "double parasites" were infective to rats. PMID- 2918438 TI - The first record of a confirmed human case of Gnathostoma doloresi infection. AB - The first case of Gnathostoma doloresi infection in a human was found in Miyazaki Prefecture, Japan. A whole length of the parasite was dissected out from biopsied skin and was identified as the third-stage larva of G. doloresi based on the morphological characteristics of the hooklets of the head bulb and also on the number of nuclei in the intestinal epithelial cells of the parasite. PMID- 2918439 TI - Effect of closantel on intrategumental pH in Schistosoma mansoni and Fasciola hepatica. AB - It has been proposed that the anthelmintic activity of the flukicide, closantel, is due to the drug's ability to interfere with the proton gradient in the parasite's mitochondria that in turn inhibits the generation of ATP by the parasite. Recent results using 31P-NMR suggest that this is not the primary target of the drug. We measured the effects of closantel on fluke intrategumental pH and observed a significant decrease (6.8 to 6.5). This decrease occurred within 10 min and at concentrations that were lower than those that produced significant changes in parasite ATP concentration. We also noted that this drug induced change in intrategumental pH was associated with a marked reduction in fluke motility. Our results, when coupled to previous reports, would suggest that closantel is a membrane-active molecule that is capable of affecting a number of helminth biochemical and physiological processes. PMID- 2918440 TI - Chemotherapy of experimental visceral leishmaniasis in the opossum. AB - Visceral leishmaniasis is a severe chronic disease of people and animals. The disease is caused by several subspecies of a protozoal organism, Leishmania donovani. If not treated, visceral leishmaniasis is often fatal. The most commonly used chemotherapeutic agents to treat the disease are pentavalent antimonials, which can be toxic, must be administered by parenteral routes, and are sometimes ineffective. In this study, meglumine antimoniate, a pentavalent antimony, was compared with WR 6026, an 8-aminoquinoline derivative, as to antileishmanial efficacy. The results indicate that either of these 2 drugs are effective in the suppression of amastigotes in the liver and spleen of the opossum. Despite the marked parasite suppression in the liver and spleen of the infected opossums, the experimental disease was fatal in all of the infected opossums, regardless of the therapy. PMID- 2918441 TI - Systematic analysis of the Diplostomidae and Strigeidae (Trematoda) AB - A systematic analysis of the genera in the Diplostomidae and Strigeidae was made using the Proterodiplostomidae as the outgroup. The Proterodiplostomidae was the family with the greatest preponderance of primitive characters and its monophyly was supported by the unique paraprostate gland. However, no character state supported the monophyly of the Diplostomidae sensu Dubois, 1970. That paraphyletic taxon was composed of 3 monophyletic groups: the pseudosuckerless Neodiplostomidae n. fam. had the most primitive character states of the 3 and its monophyly was based on characters in the neascus/neodiplostomulum metacercariae; the Bolbophoridae n. fam., with pseudosuckers, had its monophyly supported by characters present in the newly named prodiplostomulum metacercaria; and the emended Diplostomidae, also with pseudosuckers, had the most derived states and its monophyly was supported by characters present in the diplostomulum. The presence of pseudosuckers united the Bolbophoridae n. fam., the emended Diplostomidae, and the Strigeidae as a monophyletic assemblage. The Strigeidae had the most derived characters of these 3 taxa and its monophyly was supported by characters in the tetracotyle and the cup-shaped forebody and bilobed tribocytic organ of the adult. In general, the adult stages of these strigeoid families showed very conserved morphology and it was the metacercariae that possessed the innovations. The conserved adult morphology was typical of what one might expect if the intramolluscan stages were analyzed. Thus, the data were concordant with the view that the mollusc and vertebrate definitive host were the original hosts to the Digenea and that the second intermediate host and metacercaria were more recently intercalated. More specifically, the phylogeny of these groups suggested that ancestral bisegmented strigeoids originally infected reptiles, they subsequently radiated into birds with which they coevolved extensively, and on 5 separate occasions they radiated into mammals. The radiations into mammals were, by all available evidence, preceded by second intermediate host shifts from fish to amphibians. PMID- 2918442 TI - Profilicollis botulus (Van Cleave, 1916) from diving ducks and shore crabs of British Columbia. AB - Adults of Profilicollis botulus were found in 6 species of diving ducks in British Columbia including 3 new hosts: common goldeneye, Bucephala clangula (L.); Barrow's goldeneye, B. islandica (Gmelin); and greater scaup, Aythya marila (L.). The identification of the species was verified by the examination of co types and specimens from eider ducks, Somateria mollissima (L.), from Scotland and oldsquaw, Clangula hyemalis (L.), from New Brunswick. Cystacanths from the hairy shore crab, Hemigrapsus oregonensis (Dana), were similar in morphology to those from Carcinus maenas (L.) from Scotland. PMID- 2918443 TI - Effect of in vitro cultivation on the stability of resistance of Trypanosoma brucei brucei to diminazene, isometamidium, quinapyramine, and Mel B. AB - A Trypanosoma brucei brucei stock resistant to diminazene aceturate, isometamidium chloride, quinapyramine sulfate, and Mel B was grown in vitro and its response to these drugs compared to that of a drug-sensitive trypanosome stock. There was little if any change of drug sensitivity after in vitro propagation as bloodstream forms for 120, 177, and 275 days and after in vitro transformation of bloodstream forms into procyclic, epimastigote, and finally metacyclic forms. Drug resistance was stable during in vitro maintenance in the absence of drugs in both culture systems. The response of resistant and sensitive T. b. brucei to diminazene in vitro correlated with their sensitivity pattern in vivo. Thus, in vitro techniques can be used to study drug resistance in trypanosomes. PMID- 2918444 TI - Effect of age on cholinesterase activity and protein of unfed larval ticks. AB - The cholinesterase (AChE) activity and total protein in homogenates of unfed larvae of Amblyomma americanum (L.), A. cajennense (Fabricius), A. maculatum Koch, Anocentor nitens Neumann, and Boophilus microplus (Canestrini) were determined weekly in ticks 1-6 wk of age. There was a considerable variation in total protein, AChE, and the ratio of AChE to protein as the ticks aged. However, AChE activities were constant or increased with age and total protein levels were constant or decreased. No direct relationship was detected between AChE activity and total protein levels. The ratio of AChE to protein increased as the unfed larval ticks aged. PMID- 2918445 TI - Incompetence of catbirds as reservoirs for the Lyme disease spirochete (Borrelia burgdorferi). AB - We compared the relative infectivity to vector ticks of gray catbirds (Dumetella carolinensis) and white-footed mice (Peromyscus leucopus) for the Lyme disease spirochete (Borrelia burgdorferi). Of 28 catbirds captured in a site enzootic for this agent, 18 were infested by immature Ixodes dammini, the tick vector. By comparison, each of 32 mice sampled concurrently from the same site was infested, and by about 10 times as many ticks as were found infesting the 3 most commonly netted bird species. Although 76% of noninfected larval ticks placed on these mice in a xenodiagnosis became infected, none of the ticks similarly placed on 12 catbirds did so. Spirochetes were detected in ticks derived from 2 Carolina wrens (Thryothorus ludovicianus) and a common yellowthroat (Geothlypis trichas), but these species' potential contribution to infecting ticks does not compare with that of mice. Thus, although birds may help establish new foci of ticks, catbirds, at least, do not appear to contribute as reservoirs of infection. PMID- 2918446 TI - Morphology and life cycle of Schistosoma sinensium Pao, 1959, from northwest Thailand. AB - Schistosoma sinensium Pao, 1959, was first isolated from an unidentified snail in Szechuan Province, China, and was described on the basis of adult worms and eggs recovered from experimentally infected mice. We discovered snails, Tricula bollingi Davis, and rodents, Rattus rattus (L.) and Crocidura attenuata Milne Edwards, infected with S. sinensium near Fang in northwest Thailand. Adult worms were recovered from small veins immediately adjacent to the small intestine. Eggs first appeared in the feces of experimentally infected mice at 25 days postinfection. Cercariae first emerged from experimentally infected T. bollingi at 40 days postinfection. Shortly after emerging, cercariae were found at the water surface, their bodies flat against the meniscus and tails hanging free in the water column. Our morphometric results for adults and eggs from naturally infected hosts agree well with those presented in the original description. The occurrence of a lateral spine on the egg of this Asian schistosome has created some confusion as to the affinities of S. sinensium. A comparison of 8 character states, including snail hosts, cercarial behavior, geographical distribution, and morphology of life cycle stages, indicates that S. sinensium is more closely related to S. japonicum Katsurada than it is to S. mansoni Sambon. PMID- 2918447 TI - The two-factor model of self-reported mood: a cross-cultural replication. AB - The cross-cultural stability of a two-factor model of self-reported mood was studied in Israel. Sixty women and 25 men filled out a 58-adjective Mood Check List, everday for 45 consecutive days. Replicatory factor analyses demonstrated that the two-factor model of mood is applicable to both Israeli men and women and that this structure is consistent across American and Israeli cultures. Three implications of these findings are discussed. Replication of this structure in a diversified and unique culture, such as Israel, coupled with a previous replication in Japan (Watson, Clark, & Tellegen, 1984), is interpreted as lending considerable support to the assertion that this model of mood is cross-culturally consistent. Theoretical formulations and empirical findings derived and discovered in the U.S. can now be employed in planning and interpreting mood studies in Israel. The results of such studies can be incorporated within the general body of knowledge accumulating on this topic in the U.S. PMID- 2918448 TI - Indices of psychopathology in the Rorschachs of boys with severe gender identity disorder: a comparison with normal control subjects. AB - Recent clinical and empirical studies of boys with Gender Identity Disorder (GID) of Childhood suggest that severe behavioral disturbance exists beyond their feminine preoccupations. This study examines the thought organization and object representational paradigms of a sample of GID boys (n = 26) in a blind comparison with a normal subgroup (n = 18). Rorschach test protocols were used to compare the groups along these two more internal measures of personality organization. As hypothesized, the GIC group was found to have more pathological scores than the normal group on the Mutuality of Autonomy (MOA) Scale and a thought disorder hierarchy. The findings suggest that GID boys do not suffer solely from gender symptomatology but are disturbed in other aspects of their ego functioning as well. PMID- 2918449 TI - Validity of the Superiority and Goal Instability scales as measures of defects in the self. AB - A series of four canonical correlation analyses was conducted to compare the Superiority and Goal Instability scales both with personality pattern and clinical syndrome scales from the Millon Clinical Multiaxial Inventory (MCMI) and with therapist ratings of personality traits and symptom patterns using 91 clients from a cross-section of outpatient and inpatient mental health agencies. The Superiority scale was related to a pattern of social gregariousness, interpersonal exploitation, and impulsivity and Goal Instability was related to a pattern of social withdrawal, depression, and lack of ambitions and goals. These results clarify the meaning of the two self-scales as well as providing preliminary data on self-pathology and character types. PMID- 2918450 TI - Validation of a measure of perfectionism. AB - This article describes perfectionism, or the holding of and striving for unrealistically high standards, and presents two studies undertaken to investigate the convergent, discriminant, and predictive validity of the Perfectionism Scale (PS; Burns, 1980). College students in the first study completed the PS, several other measures of high standards, and measures of constructs that, conceptually, are differentially related to perfectionism. Correlational analyses indicated that the Perfectionism Scale has convergent and discriminant validity and seems to measure self-oriented perfectionism. The second study attempted to determine the predictive validity of the PS by testing a vulnerability model of subclinical depression outlined in Hewitt and Dyck (1986). PS scores were used to predict depressed mood changes in female college students following failure on important and unimportant tasks. As expected, the results indicated that perfectionism interacted with failure on important versus unimportant tasks to produce dysphoric mood. Evidence for the predictive validity of the PS was thus shown. Several directions for future research are discussed. PMID- 2918451 TI - Lao Depression Inventory. AB - There are no measurement tools that accurately measure depression among Lao refugees. The overall purpose of this research was to complete the development and validation procedures for the Lao Depression Inventory (LDI). The study consisted of 216 Ethnic Lao refugees. A clinical interview and 164 true/false questions were administered to identify specific items which could identify depression among the Ethnic Lao people. All items were administered in both English and Lao. Overall, 78 of the 164 items differentiated groups of depressed and nondepressed Lao at the .01 level. Results of validation procedures showed that a 30-item scale had an accuracy rate of 89% in identifying the presence of depression in the validation group; the hit-rate for the same items and cutoff was 92% in the cross-validation group. Potential uses of the scale are discussed. PMID- 2918452 TI - It only takes one psychologist to demonstrate the impact of psychological assessment. AB - Evidence is needed in the field of psychological assessment of psychiatric patients to verify if test findings actually influence the clinical processes of diagnosis, treatment, case disposition, and outcome. Those who perform many assessments can conduct limited experiments to measure these effects. One such study is presented. It is a quasi-experiment in which the value of the psychologist's diagnostic recommendations to treating psychiatrists was measured. Diagnoses at admission, at subsequent psychological evaluation, and at discharge were compared among 70 patients referred to a clinical diplomate from the American Board of Professional Psychology (ABPP) for assessment. The psychiatrists who had referred the patient agreed with the psychologist's diagnosis in 94% of the cases. Agreement was high even when the psychologist had disagreed with the admitting psychiatrists' diagnoses. Despite imperfections in research design, the study demonstrates that solo practitioners can evaluate the impact of assessment. Other possibilities for study are presented, as are reasons for the significant findings of this study. PMID- 2918453 TI - Correlates of the Egocentricity Index in child and adolescent outpatients. AB - This study examined the Rorschach and MMPI covariates of Exner's Egocentricity Index, 3r + (2): R, in a sample of child and adolescent outpatients (n = 46). Consistent with previous findings on adult psychiatric inpatients (Barley, Dorr, & Reid, 1985), significant positive correlations were obtained between the Index and M, FM, X + %, and D when controlled for the number of protocol responses. The Egocentricity Index was negatively associated with lambda and, in a subsample of adolescents (n = 19), depression scores. The index bore no significant relationship to either Minnesota Multiphasic Personality Inventory (MMPI) validity or clinical scales, also congruent with earlier investigations. Implications for the interpretation of childrens' Egocentricity Indices are discussed. PMID- 2918454 TI - Diagnosis of major depression by self-report. AB - The Symptom Checklist-90 (SCL-90), Millon Clinical Multiaxial Inventory (MCMI), and Minnesota Multiphasic Personality Inventory (MMPI) test profiles of inpatients and outpatients with DSM-III major depression (n = 48) were contrasted with the test profiles of a control group of patients with diverse psychiatric disorders (n = 68). In addition, the diagnostic efficiency of the relevant depression subscales for the diagnosis of major depression were examined. The results indicated that the three self-report tests may be used to diagnose DSM III major depression, and that the depressed patients had characteristic test profiles. PMID- 2918455 TI - A psychometric study of the PRF ANDRO Scale. AB - This study investigated the adequacy of the items in the PRF ANDRO Masculinity (M) and Femininity (F) Scales, in terms of the content themes specified by Berzins, Welling, and Wetter (1978), and empirically tested their appropriateness using Bem's (1974) criteria. Results indicated that the PRF ANDRO M and F scales contain a large proportion of items that are theoretically irrelvant and that did not satisfy Bem's criteria. In addition, these scales were found to contain several items with low content saturation. Implications of the results are discussed. PMID- 2918456 TI - Standardizing the administration of the Profile of Mood States (POMS): development of alternative word lists. AB - Although standard administration procedures are essential for valid inference making, current Profile and Mood States (POMS; McNair, Lorr, & Droppleman, 1971) protocol forces each examiner, when asked for assistance, to provide subjects extemporaneously with a word or phase that is: (a) synonymous with the original item, (b) located nowhere else on the instrument, and (c) more meaningful to the subject than the original item. The purpose of this article is to describe an empirically based extension of current POMS protocol designed to augment uniformity in administration procedures by providing examiners with a standardized list of alternatives to be referred to when questions concerning the meaning of POMS items arise. A multiphase survey procedure was employed to generate and refine alternative items. A series of alpha (internal consistency) reliabilities, calculated for the POMS subscales after each alternative was substituted, revealed little change in subscale homogeneity resulting from the substitution of the alternatives. PMID- 2918457 TI - The assessment of personality characteristics in depressed and dependent psychiatric inpatients. AB - The diagnosis and treatment of depression may be complicated by the presence of excessive dependency needs. Previous research has found stable personality traits useful in identifying depressive subtypes. This study was designed to assess the personality characteristics of 106 psychiatric inpatients. Subjects were grouped according to the presence or absence of two primary dimensions: depression and dependency. Results indicated that both depression and dependency were significantly related to various indices of psychopathology. Main effects were more useful than interactions, implying that depression and dependency both affect symptomology directly rather than interactively. Although the assessment of personality traits may be complicated by the presence of a major psychiatric disorder, results from our study suggest that the assessment of both Axis I and Axis II variables can be useful in understanding the current clinical picture. PMID- 2918458 TI - Predicting depression using earliest childhood memories. AB - In order to investigate the utility of earliest childhood memories (EMs) in clinical assessment, this study investigated the value of EMs in predicting naturally occurring depressive mood states. Of interest were those features of EMs that discriminate depressed from nondepressed individuals. Subjects were 212 undergraduate volunteers who completed the Beck Depression Inventory, the Profile of Mood States, and a self-administered EM questionnaire. Utilizing thematic predictors derived from cognitive and psychodynamic theories of depression, depressed subjects were differentiated from nondepressed subjects at a rate significantly greater than chance, p less than .001, with a highly respectable estimate of cross-validation shrinkage. The findings demonstrate the phenomenon of mood dependent recall in autobiographical memory, namely, that memory attributes are strongly influenced by current mood state. Consistent with psychodynamic theories of depression and in contrast to cognitive theory, depressive mood states appear to facilitate retrieval of memory schemas involving deprivation and disturbing human interaction. Schemas involving loss of control, failure, or reactions to noncontingent reinforcement (perceptions of the self as agent) appear less salient than relationship schemas (perceptions of the self as related) in depressive experience. PMID- 2918459 TI - An MMPI description of the narcissistic personality. AB - This study developed a Minnesota Multiphase Personality Inventory (MMPI) description of the narcissistic personality in a nonclinical population. The Narcissistic Personality Inventory (NPI) and the MMPI were administered to two samples of 57 and 173 subjects. A correlational analysis produced a cross validated positive relationship between narcissism and MMPI mania (Ma) and cross validated negative relationships between narcissism and MMPI depression (D), psychasthenia (Pt), social introversion (Si), anxiety (A), repression (R), and ego control (Ec). A correlational analysis of the 7-factor components of the NPI (Authority, Exhibitionism, Superiority, Vanity, Exploitativeness, Entitlement, and Self-Sufficiency) and the MMPI validity, clinical, commonly scored, and content scales suggests that the seven NPI components reflect different levels of psychological maladjustment. Narcissistic Entitlement and Exploitativeness reflect the most maladjustment, whereas narcissistic Authority reflects the least maladjustment. In addition, a profile analysis of the high NPI scorers suggest that a 98/89 MMPI profile with an elevated F score is most representative of the narcissistic personality in nonclinical samples. PMID- 2918460 TI - Rorschach records of Nazi war criminals: a reanalysis using current scoring and interpretation practices. AB - The Nuremberg trials focused worldwide attention on 22 Nazi war criminals. Rorschach Inkblot tests were administered to these Nazi leaders in an attempt to understand the Nazi personality. Past studies which have described and interpreted these Rorschach records have made at least two types of errors in their analyses. One is that of overinterpretation and excessive inference. A second common error has been the failure to detect meaningful distinctions between protocols that represent significant differences in personality style. This latter error is shown in repeated attempts to group all Nazi protocols into one distinct "Nazi personality." This investigation attempted to quantify the analysis of these Nazi Rorschach records, specifically those Nazi leaders who were sentenced to life imprisonment or execution for their war crimes against humanity, by utilizing Exner's (1985a) standardized Comprehensive Scoring System as well as computerized objective interpretation software based on the Exner system (1986). This modern analysis of the Rorschach records demonstrates that the Nazi war criminals cannot be grouped together into one specific mental disorder that would adequately characterize these diverse individuals. The varying degrees of psychopathology of the Nazi leaders are illustrated by analyses of individual Rorschach protocols. PMID- 2918461 TI - Intravenous recombinant tumor necrosis factor in the treatment of AIDS-related Kaposi's sarcoma. AB - Tumor necrosis factor (TNF) has demonstrated antitumor activity against a variety of tumors and is particularly cytotoxic to capillary endothelial cells, which are the presumed cell of origin of Kaposi's sarcoma. We evaluated the toxicity and clinical antitumor and antiretroviral effects of recombinant TNF administered at a once weekly dose of 100 micrograms/m2 intravenously for 8 weeks in five men with AIDS-related Kaposi's sarcoma and without prior opportunistic infection. One patient was removed from study at week 4 due to rapid progression of Kaposi's sarcoma, another patient with stage IV disease and a pretreatment CD4 count of 11 developed fever, hypotension, and pneumonia at week 7 and died 8 days after discontinuing recombinant TNF. No pathogenic organisms were isolated. He had marked eschar formation of his Kaposi's sarcoma lesions, particularly in areas previously exposed to radiation therapy. Uniform toxicities included fevers, rigors, and headaches during drug infusion that were ameliorated by prophylactic meperidine hydrochloride and acetaminophen. All experienced fatigue and three had arthralgias. One patient had transient hypotension which corrected with i.v. fluids. No significant hematologic, hepatic, or renal toxicities were seen. All patients had some progression of their Kaposi's sarcoma on study. There was no change in CD4 or CD8 count or in CD4:CD8 ratios. Serum human immunodeficiency virus (HIV) p24 antigen levels increased greater than 50% in three patients. We conclude that, as a single agent, at a dose of 100 micrograms/m2 recombinant TNF by i.v. infusion has no obvious antitumor or antiretroviral effects in patients with AIDS-related Kaposi's sarcoma. PMID- 2918462 TI - Seroconversion, sexual activity, and condom use among 2915 HIV seronegative men followed for up to 2 years. AB - A cohort of 2915 HIV-1-seronegative men from the four centers of the Multicenter AIDS Cohort Study (MACS) was followed at 6 month intervals for 24 months to identify men who developed antibodies to HIV-1. Two hundred thirty-two men (8%) seroconverted. The highest attack rate was among men who reported practicing both receptive and insertive anal-genital intercourse. The attack rate among men who reported practicing receptive but not insertive intercourse was 3.6 times higher than among men practicing insertive intercourse although those practicing insertive only reported 38% more different partners. Only two men seroconverted who reported not practicing analgenital intercourse in the 12 month prior to the first antibody-positive visit. Because men were followed every 6 months, one of these men could have been infected within 6 months of the actual development of HIV-1 antibodies. The seroconversion rate was significantly lower among men who reported using condoms with all their partners. The results of this study (a) reaffirm that receptive anal-genital intercourse is the major route of infection among homosexual men of HIV-1, (b) suggest that there is a low risk of HIV-1 infection to the insertive partner in anal-genital intercourse, (c) suggest that infection may rarely occur through sexual activities other than anal-genital intercourse, (d) provide evidence that condoms as currently used by men in the MACS provide significant but not complete protection against HIV-1 infection, and (e) suggest that the number of men in the homosexual community engaging in high risk behavior is declining. PMID- 2918463 TI - The conditional latency distribution of AIDS for persons infected by blood transfusion. AB - Knowledge of the latency period between infection with HIV and the onset of clinical AIDS is important both to establish prognosis for infected individuals and to model the spread of HIV. This paper presents nonparametric analyses of conditional distribution of latency based on data from 1,206 persons who developed AIDS as a result of contaminated blood transfusions. Among persons who develop AIDS within 8 years of infection, there are no significant differences in the distributions of males and females. The conditional latency distribution of infants is significantly shorter than that of other transfusion cases, yet considerably longer than has previously been reported. PMID- 2918464 TI - HIV-2-associated AIDS and HIV-2 seroprevalence in Bissau, Guinea-Bissau. AB - During a 6-month period in 1987, we examined patients clinically suspected of the acquired immune deficiency syndrome (AIDS) at the national hospital in Bissau, the capital of Guinea-Bissau, and found 20 cases that fulfilled the criteria for AIDS. The two most prevalent major symptoms were weight loss and diarrhea, and the most common minor symptoms generalized lymphadenopathy and generalized dermatitis. Six of 20 patients died within a couple of months. Nineteen of 20 patients were tested for human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) antibodies and were shown to be HIV-2 seropositive. During the same time period, a seroprevalence study of HIV-2 and HIV-1 was carried out, including 2,122 patients or healthy persons in Bissau. Antibodies to HIV-2 were demonstrated by enzyme-linked immunosorbent assay and verified by Western blot analysis in 8.6% (46/535) of prenatal women, in 7.9% (9/114) of women attending a family-planning clinic, in 4.4% (19/427) of applicants for scholarships, in 17.6% (16/91) of blood donors tested during the first 2 months and 5.3% (10/189) of blood donors tested during the following months, in 5.7% (2/35) of police officers, in 36.7% (11/30) of female prostitutes, in 15.8% (97/614) of outpatients suspected of having tuberculosis, and in 55.2% (48/87) of patients clinically suspected of AIDS or AIDS-related disease. One of 2,001 subjects tested had antibodies specific for HIV-1. Another subject had an antibody pattern compatible with both HIV-1 and HIV-2 infections.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918465 TI - Stereoselectivity of styrene oxidation in microsomes and in purified cytochrome P 450 enzymes from rat liver. AB - The stereochemistry of the cytochrome P-450(P-450)-dependent oxidation of styrene to styrene 7,8-oxide (SO) enantiomers was evaluated with rat hepatic microsomes and with individual rat liver P-450 enzymes in reconstituted monooxygenase systems. The stereoselectivity of the monooxygenase reaction with styrene was determined by high-performance liquid chromatographic analysis of the glutathione conjugates formed quantitatively from SO, the product of the monooxygenase reaction. Hepatic microsomes from control rats oxidized styrene at a rate of 13.1 +/- 4.5 nmol/min/nmol of P-450 and with a ratio of the amount of the (R)-styrene 7,8-oxide enantiomer to the amount of the (S)-styrene 7,8-oxide enantiomer (R/S) SO ratio of 0.65 +/- 0.1. These values were determined under incubation conditions in which epoxide hydrolase activity was inhibited by cyclohexene oxide, and at least 95% of the SO formed was converted enzymatically to glutathione conjugates. Treatment of rats i.p. with phenobarbital (PB) or beta naphthoflavone (beta NF) caused changes in both parameters. Whereas the rates of oxidation in hepatic microsomes prepared from PB-treated rats was unchanged at 15.4 +/- 7.5 nmol/min/nmol of P-450 and decreased in hepatic microsomes from beta NF-treated rats to 9.4 +/- 2.8 nmol/min/nmol of P-450, the preference for formation of the R-enantiomer increased as the R/S ratio changed to 0.92 +/- 0.1 for PB and 1.25 +/- 0.1 for beta NF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918466 TI - Toxicity of the HMG-coenzyme A reductase inhibitor, lovastatin, to rabbits. AB - Lovastatin, a specific inhibitor of the rate-limiting enzyme in cholesterol biosynthesis, HMG-CoA reductase, has been shown to be highly effective in lowering serum cholesterol in animals and humans and thus represents a promising approach to the treatment and prevention of cardiovascular disease. During the preclinical safety assessment of lovastatin, oral doses that were tolerated by dogs, rats and mice were found to be lethal to rabbits in subacute studies. Postmortem findings in rabbits consisted of centrilobular hepatic necrosis, frequently accompanied by renal tubular necrosis and occasionally gallbladder necrosis. The liver lesions were associated with up to 300-fold elevations in serum aspartate and alanine aminotransferase activities, whereas the kidney lesions resulted in accumulations of serum urea nitrogen and creatinine. The organ damage was preceded by a progressive decline in food consumption and loss of body weight. All histopathological and serum biochemical changes induced by lovastatin were completely prevented by coadministration of mevalonate, the product of the inhibited HMG-CoA reductase enzyme. In addition, administration of mevalonate after the onset of lovastatin-induced hepatotoxicity effectively reversed the toxicity despite continued drug treatment. These findings indicated that the toxicity of high doses of lovastatin to rabbits is a consequence of a highly exaggerated pharmacologic action in blocking mevalonate synthesis. However, supplementation of lovastatin-treated rabbits with oral doses of the major product of mevalonate metabolism, cholesterol, paradoxically enhanced the liver and kidney damage, which suggested that the toxicity of lovastatin stemmed from depletion of a nonsterol metabolite(s) of mevalonate critical for cell viability. PMID- 2918467 TI - Targeting small unilamellar liposomes to hepatic parenchymal cells by dose effect. AB - A major research goal of liposome pharmacology is the selective delivery of drugs to target cell populations while minimizing extraction by phagocytic macrophages and blood monocytes of the reticuloendothelial system. The liver is an ideal organ for studying targeting strategies using a variety of liposomes, inasmuch as its discontinuous capillaries have fenestrae through which liposomes less than 0.2 microns in diameter may escape into the extravascular space. In a previous kinetic study, we proposed that the hepatic uptake of small unilamellar vesicles (SUV) in mice was compatible with a model of uptake involving dual, parallel pathways. One is a saturable, phagocytic pathway of uptake mediated by Kupffer cells, the other is a nonsaturable, pinocytotic pathway of uptake mediated by parenchymal cells, favoring the latter pathway at high liposomal dose (Beaumier et al., 1983). In the present study, we demonstrated by the techniques of liver cells fractionation that the uptake of either the bovine brain sphingomyelin/cholesterol (2:1; mole/mole) SUV or distearoyl phosphatidylcholine/cholesterol (2:1; mole/mole) SUV by hepatic parenchymal cells was enhanced markedly by increasing the amount of injected dose of SUV. As high as 85 to 90% of the total liver dose can be attributed to the uptake of SUV by the hepatic parenchymal cells alone, when the injected dose reaches at or above 7.5 to 10 micrograms of lipid per g b.wt. The dose effect on the uptake of liposomes by hepatocytes appears to be a general phenomenon of neutral SUV. Our data suggested that blockade by dose permits a feasible approach to target SUV to hepatic parenchymal cells. PMID- 2918468 TI - Effects of acute and chronic clozapine and haloperidol on in vitro release of acetylcholine and dopamine from striatum and nucleus accumbens. AB - The purpose of this investigation was to determine if striatal or nucleus accumbens dopamine (DA) release, ACh release or DA receptor function were altered by acute and chronic haloperidol or clozapine treatment in a manner consistent with the reported pharmacological effects of each drug on A9 and A10 DA cell bodies and projection areas, when experiments were performed without a drug-free, or washout, period after drug treatment. The release of neurotransmitters reported here was evaluated using a slice-superfusion assay system. Transmitter release was induced either by an electrical field (for DA and ACh) or by application of either amphetamine or amfonelic acid (DA only). Dopaminergic receptor function was assessed by inhibiting electrically stimulated ACh release with in vitro TL-99 (a dopaminergic agonist) and by reversing that inhibition with in vitro neuroleptics or with ex vivo experimental paradigms (the in vitro analysis of transmitter release subsequent to in vivo drug administration). These data suggest that although there are differences between haloperidol and clozapine, there is no difference between the degree of postsynaptic DA receptor blockade produced that can be attributed to the duration of neuroleptic treatment. Chronic clozapine (20 mg/kg x 21 days) reversed TL-99-induced inhibition of ACh release in the nucleus accumbens only, whereas chronic haloperidol (0.5 mg/kg x 21 days) produced a similar reversal in both brain areas. One possible explanation for the lack of effect of chronic clozapine treatment in the striatum is that carrier-mediated (amphetamine-stimulated) DA release is enhanced in the striatum but not in the nucleus accumbens, suggesting that the potential DA receptor block in the striatum may be compromised by enhanced striatal DA levels. Acute haloperidol (0.5 mg/kg) was found to increase electrically stimulated ACh release in the striatum and DA release in the nucleus accumbens. Tolerance developed in the striatum, but not the nucleus accumbens, with repeated administration. However, acute clozapine had no effect on ACh release in either area, but it was found to enhance DA release in the striatum, an effect to which tolerance developed with chronic administration. Further, comparison of these data with data obtained using haloperidol and clozapine in vitro suggests that it is unlikely that these effects are due to residual drug still present in these tissues at the time of experimentation. These data are discussed with regard to electrophysiological and pharmacological differences observed between clozapine and haloperidol on the activity of A9 and A10 DA cells after chronic neuroleptic treatment. PMID- 2918469 TI - Uptake of nephrotoxic S-conjugates by isolated rat renal proximal tubular cells. AB - Freshly isolated, rat renal proximal tubular cells have been widely used to study the biochemical mechanisms of cysteine and homocysteine S-conjugate-induced cytotoxicity. Because cellular transport may be an important determinant of S conjugate-induced nephrotoxicity, the characteristics of the transport of nephrotoxic cysteine S-conjugates and analogs were studied in rat renal proximal tubular cells. Time- and concentration-dependent uptake of S-(1,2-dichlorovinyl) L-cysteine (DCVC) and S-(1,2-dichlorovinyl)-L-homocysteine (DCVHC) into cells were observed; higher concentrations were accumulated in the presence of aminooxyacetic acid (AOAA), an inhibitor of cysteine conjugate beta-lyase, indicating that AOAA does not inhibit transport. Saturable sodium-dependent and sodium-independent transport processes were identified; approximately 50% of DCVC uptake, but only 30% of DCVHC uptake, was sodium-dependent. Competition studies indicated that the probenecid-sensitive organic anion transport system, which is sodium-dependent, and system L, which is sodium-independent, participate in the renal proximal tubular uptake of both S-conjugates. In addition, DCVHC uptake occurs by the sodium-dependent system ASC and system A. The greater degree of sodium independence of DCVHC uptake as compared to that of DCVC indicates that system L plays a greater role in DCVHC uptake than it does in DCVC uptake. Both sodium-dependent and sodium-independent uptake of the nonmetabolizable and nontoxic alpha-methyl analogs, S-(1,2-dichlorovinyl)-DL-alpha-methylcysteine and S-(1,2-dichlorovinyl)-DL-alpha-methylhomocysteine, were observed at rates comparable to those of DCVC and DCVHC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918470 TI - Glucose utilization in the rat brain during chronic morphine treatment and naloxone-precipitated morphine withdrawal. AB - Rates of local cerebral glucose utilization (LCGU) were measured in morphine dependent and morphine-abstinent rats. Morphine pellets were implanted s.c. (one pellet 7 days before glucose utilization measurement and two pellets 4 days before the measurement) to produce opioid dependence. LCGU rates in 85 brain regions of placebo- and morphine-pelleted rats were similar. In contrast, LCGU rates, 5 hr after implantation of one morphine pellet, were decreased significantly in six areas. The lack of a chronic morphine effect on LCGU suggests tolerance to morphine. Additional support for this view was that an additional dose of morphine (8 mg/kg s.c.) in morphine-dependent rats was also ineffective in altering LCGU and in an antinociception (hot plate) test. Furthermore, plasma morphine levels in chronically treated animals were greater than those in acutely treated animals. Naloxone-precipitated morphine withdrawal enhanced LCGU, most notably in thalamic and limbic areas, but also in some hypothalamic and hindbrain regions. The findings identify brain areas that may be important in the opioid abstinence syndrome. Furthermore they suggest that adaptations in the brain produce tolerance to morphine, reflected in LCGU rates and latencies in the hot-plate test. PMID- 2918471 TI - Environmental determinants of enhanced sensitivity to the behavioral effects of naltrexone. AB - Dose-effect curves for naltrexone were determined in three squirrel monkeys studied sequentially under four different schedule conditions: a schedule of shock postponement; a fixed-interval schedule of shock presentation; a fixed ratio schedule of food presentation; and a fixed-ratio schedule of stimulus-shock termination. In general, responding under the shock-postponement or the fixed interval schedules was decreased minimally by doses of naltrexone up to 30 mg/kg, and these effects were not altered appreciably after daily injections of naltrexone under the fixed-interval schedule. Under the fixed-ratio schedule of food presentation naltrexone (0.3 to 10 mg/kg) produced dose-related decreases in responding, and after repeated daily injections of naltrexone the dose-effect curve was shifted more than 3-fold to the left. Under the fixed-ratio schedule of stimulus-shock termination, however, this supersensitivity to naltrexone was not apparent: responding was decreased appreciably only after 17.6 mg/kg of naltrexone. When the fixed-ratio schedule of food presentation was reinstated, the supersensitivity to naltrexone observed previously under this schedule was not evident initially, but reappeared quickly in two of the monkeys. The greater rate-decreasing effects of naltrexone under the fixed-ratio schedules compared to the other schedules may reflect a dependency related to the control rate of responding. Supersensitivity to naltrexone occurred only under the fixed-ratio schedule of food presentation and could be reversed temporarily by intervening exposure to the schedule of stimulus-shock termination. These results extend earlier findings that the behavioral effects of drugs can be dependent upon both past and present environmental influences. PMID- 2918472 TI - Electrophysiological effects of ACC-9358, a novel class I antiarrhythmic agent, on isolated canine Purkinje fibers and ventricular muscle. AB - Class I antiarrhythmic agents are heterogeneous with respect to their cardiac electrophysiological effects and have been subdivided into three categories: la, lb and lc. The purpose of the present study was to determine the classification and investigate the mechanism of action of ACC-9358 [4-hydroxy-N-phenyl-3,5-bis (1-pyrrolidinyl-methyl)benzamide], a novel class I antiarrhythmic agent currently under clinical investigation. The effects of ACC-9358 on action potentials from isolated canine Purkinje fibers and ventricular muscle were examined using standard microelectrode techniques. In Purkinje fibers, ACC-9358 (1-50 microM) exerted a dose-dependent reduction in maximum upstroke velocity (Vmax) and action potential duration at 50 and 90% repolarization (APD50 and APD90). The reduction of Vmax was voltage-dependent (greater at an extracellular potassium concentration of 6 mM than at 2.7 mM), frequency-dependent (greater at a basic cycle length of 500 than at 2000 msec) and very slow in onset (rate constant of 0.017 action potentials-1) and offset (recovery half-time of 66.9 sec). In Purkinje fibers, ACC-9358 attenuated the action potential shortening effects of lidocaine but not that of nicardipine or nicorandil and shortened APD50 to a greater extent at a basic cycle length of 2000 than at 500 msec. In ventricular muscle, ACC-9358 (1-50 microM) exerted a dose-dependent reduction in Vmax and prolongation of APD50 and APD90.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918473 TI - Studies on inhibition of angiotensin II receptors in rabbit adrenal and aorta. AB - Angiotensin II (AII) labeled with 125I binds to rabbit adrenal cortical membranes over a concentration range from 0.5 to 20 nM at an apparent single site with a KD of 5 nM. This binding was inhibited in a surmountable fashion with respect to AII by the peptide analogs sarcosine1 (Sar1),Leu8AII and Phe4, Tyr8 AII when added to the incubation media concomitant with AII addition. With a 30-min preincubation, however, the former inhibitor displayed nonsurmountable kinetics whereas the profile of the latter was unaffected. In rabbit aortic strips with the same preincubation time, the Sar1Leu8AII analog was a nonsurmountable antagonist of the contractile effect of AII whereas the inhibition produced by Phe4,Tyr8AII was surmountable by increasing agonist (AII) concentrations. The inhibitory effect of the former was maintained after repeated washing of the tissue whereas that of the latter was readily reversible. Addition of Phe4,Tyr8AII to the bath 5 min before preincubation protected the tissue from the prolonged AII inhibition by Sar1,Leu8AII. These findings indicate different kinetic modes of AII inhibition by these two antagonists. Phe4,Tyr8AII behaves as a reversible, competitive inhibitor of AII binding, whereas Sar1,Leu8AII combines with the AII receptor in a slowly dissociable manner and is therefore not readily displaced by AII. PMID- 2918474 TI - Contrasting effects of verapamil and nifedipine on pH of ischemic myocardium in the dog. AB - It remains unknown whether the actions of verapamil to depress and nifedipine to enhance contractile function of ischemic myocardium influence the degree of myocardial ischemic injury. Thus, we measured intramyocardial pH using fiberoptic pH probes in 43 anesthetized open-chest dogs pretreated for 30 min with verapamil, or nifedipine in doses that decreased aortic pressure 10 to 15 mm Hg before ligation of the left anterior descending coronary artery for 15 min. Drugs were continued during the 15-min ischemic period until the animals were euthanized without reperfusion: verapamil, 10-20 micrograms/kg/min and nifedipine, 2 to 4 micrograms/kg/min i.v. Verapamil-treated dogs showed higher pH of ischemic subendocardium after 15 min ischemia (6.75 +/- 0.07) than did the nifedipine (6.48 +/- 0.04) or placebo (6.43 +/- 0.05) groups, even if the animals were paced (6.71 +/- 0.11) to prevent the negative chronotropic effect of verapamil (P less than 0.01). Neither verapamil nor nifedipine changed collateral myocardial blood flow from 0.10 +/- 0.02 in the subendocardium and 0.17 +/- 0.03 ml/min/g in the subepicardium. Left ventricular function estimated by left ventricular dp/dt was depressed 15% by verapamil and enhanced 26% by nifedipine. Thus, verapamil, but not nifedipine, relieves acidosis of ischemic myocardium after acute coronary occlusion in doses that sustain a 10 to 15 mm Hg decrease in aortic pressure. Nifedipine, in doses that produced the same 10 to 15 mm Hg decrease in mean aortic pressure, did not increase intramyocardial pH, as it enhanced contractile function, estimated by left ventricular dp/dt.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918475 TI - Block of 45Ca uptake into synaptosomes by methylmercury: Ca++- and Na+ dependence. AB - Block of Ca++ influx into isolated nerve terminals by the neurotoxicant methylmercury (MeHg) was studied for its dependence on extracellular Ca++ and Na+. Depolarization-independent entry of 45Ca++ was determined in rat forebrain synaptosomes incubated in 5 mM K+ solution. 45Ca++ uptake was similarly measured after 1 ("fast" phase) or 10 sec ("total") of elevated K+ (41.25 mM)-induced depolarization or after 10 sec of elevated K+-induced depolarization after synaptosomes had been predepolarized for 10 sec in Ca++- and MeHg-free solutions ("slow" phase). In 5 mM K+ solutions, MeHg concentrations of 125 microM and greater significantly reduced synaptosomal 45Ca++ uptake measured during 1 or 10 sec of incubation. In K+-depolarized synaptosomes, the estimated IC50 for block of total, fast and slow 45Ca++ uptake by MeHg is 75 microM; 250 microM MeHg reduced uptake by approximately 90%. The reversibility of block by extracellular Ca++ was tested by increasing the extracellular Ca++ concentration from 0.01 to 1.15 mM. When compared to control, 50 microM MeHg reduced total uptake of 45Ca++ by greater than or equal to 70% and reduced fast uptake by 20 to 60% at all concentrations of extracellular Ca++ tested. At Ca++ concentrations of 0.01 to 0.15 mM, MeHg (50 microM) reduced slow uptake by 75 to 90%, but did not affect slow uptake at higher Ca++ concentrations (greater than or equal to 0.30 mM). When the dependence of block of 45Ca++ uptake on extracellular Na+ was tested, equivalent levels of inhibition were caused by MeHg (25 microM) for fast uptake by synaptosomes in Na+-containing and Na+-free solutions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918476 TI - Effect of ouabain on the concentration of free cytosolic Ca++ and on contractility in cultured rat cardiac myocytes. AB - Effects of ouabain on [Ca++]i and on contractility was measured in quin2 and fura2 loaded cultured neonatal rat cardiac myocytes. Addition of ouabain (5 x 10( 8) to 5 x 10(-6) M) to cultured myocytes exposed to balanced buffered salt solution (BSS) caused a transient increase in [Ca++]i, followed by slow oscillations for about 10 min, and by an elevated steady state level of [Ca++]i thereafter. Concentrations of ouabain between 10(-7) and 5 x 10(-7) M caused an increase in the amplitude of systolic motion (ASM) whereas concentrations above 10(-6) caused a decrease in the ASM, an increase in the beating frequency and an upward shift of the base line, indicating impaired relaxation. When ouabain was added to cardiac myocytes exposed to Ca++-free BSS the increase in [Ca++]i was not observed, but only a transient decrease. To investigate the effect of [K+]o on the ouabain-induced changes in [Ca++]i, ouabain was added to cells exposed to BSS containing low K+ concentration (1 mM instead of 5 mM in balanced BSS). In this medium the increase in ASM by ouabain was similar to that in balanced BSS. Addition of ouabain caused a transient decrease in [Ca++]i. There was no initial increase in [Ca++]i and the steady state level of [Ca++]i was not elevated as compared with the same cells before the addition of ouabain. Similar results were observed in cells loaded with quin2 or with fura2. In view of these results the mechanism of action of ouabain on cardiac myocytes is discussed. PMID- 2918477 TI - Pharmacokinetic patterns of repeated administration of antidepressants in animals. II. Their relevance in a study of the influence of clomipramine on morphine analgesia in mice. AB - Many studies have shown tricyclic antidepressants (TCAs) to potentiate morphine analgesia, but more recent work, using different modes of administration, has revealed inhibition of morphine analgesia by TCAs. The influence of different modes of administration of clomipramine (CMI) on morphine analgesia assessed by the hot-plate test was studied in mice. The administration procedure was based on the pharmacokinetic parameters of CMI determined in the strain used. Acute and chronic (i.e., every half-life of 130 min for five half-lives) administration of CMI (10 or 20 mg/kg i.p.) had opposite effects; the former potentiated morphine analgesia and the latter inhibited it. Five closely repeated administrations (i.e., every 40 min) suppressed the potentiation without producing inhibition. The time course of the influence of CMI showed that the inhibition of morphine analgesia observed after repeated administration of a given dose of CMI occurred if the latter was present for sufficient time; this time decreased when the dose of CMI was increased. Moreover, comparison with literature data shows the importance of standardized patterns of repeated administration: the variability in the frequency of repeated administration and in the time-lag between the last injection of TCA and the test may account for the varying results observed. The discrepancies in the literature regarding TCA/morphine interaction are thus only apparent, and arise merely from varying conditions. Possible mechanisms for the CMI-morphine interaction are discussed: involvement of opiate receptors and/or the serotonergic system. PMID- 2918478 TI - Regulation of rat uterine steroid receptors by nomegestrol acetate, a new 19-nor progesterone derivative. AB - The regulatory effects of nomegestrol acetate (NOM-Ac: 17 alpha-acetoxy-6 alpha methyl-19-nor-pregna-4,6-diene-3,20-dione), a new 19-nor-progesterone derivative, active p.o. progestin, were studied on rat uterine estrogen (ER) and progestogen receptor (PgR) levels. The actions of estradiol (E2), progesterone (P) and various progestins were investigated. The effects of E2 were reproduced with 5 micrograms/animal: a 2-fold increase in activated ER level in the nucleus at 30 min, 2-fold stimulation of cytosolic ER replenishment at 48 hr and a 4-fold induction of PgR synthesis at 48 hr. The negative regulatory effects of P were also reproduced at doses ranging from 0.25 to 2 mg/animal: inhibition of basal and E2-stimulated cytosolic ER replenishment and inhibition of E2-induced PgR synthesis. NOM-Ac reproduced these negative regulatory effects. The 50% effective doses in reducing estrogen receptor levels and the corresponding potencies relative to P showed NOM-Ac to be 2.4-fold more active than P and to present, when compared to the other progestins, the highest antiestrogenic capacity. Furthermore, in contrast with norethisterone acetate, a 19-nor-testosterone derivative, it was completely devoid of estrogenic potency. PMID- 2918479 TI - Effect of alpha-1-acid glycoprotein, albumin and palmitic acid on the brain and salivary gland extraction of warfarin in rats. AB - The effect of plasma protein binding of warfarin on its transfer into the brain and salivary gland was investigated using alpha-1-acid glycoprotein and human serum albumin (HSA) in combination or not with palmitic acid. The tissue extraction of [14C] warfarin relative to [3H]water was determined by intracarotid injection technique in male Wistar rats. The tissue extraction of warfarin varied inversely with the concentration of added serum protein, (HSA and alpha-1-acid glycoprotein), and addition of palmitic acid to HSA diminished the extraction. The fraction of drug uptaked by tissue (tissue available fraction) was always dramatically greater than the in vitro free drug fraction, and this was interpreted as an enhanced in vivo drug dissociation from the binding protein. The fraction of drug uptake by salivary gland was closer to the in vitro free fraction than the fraction of drug uptake by brain tissue. The addition of palmitic acid to HSA induced parallel changes in the in vitro free fraction of warfarin and in the brain tissue or salivary gland extraction of warfarin. These data indicate that a part of protein-bound warfarin (as determined in vitro) is available for tissue extraction via an enhanced in vivo dissociation of the drug protein complex in the tissue microcirculation. The in vitro data were fitted to a saturable model of binding whereas the in vivo data could satisfactorily fit a model dealing with a nonsaturable model of binding, and this is probably the result of the several-fold increase in the in vivo dissociation constant. PMID- 2918480 TI - Effects of acute and chronic prenatal nicotine treatment on central catecholamine systems of male and female rat fetuses and offspring. AB - The effect of acute and chronic prenatal administration of nicotine on central catecholamine systems was studied in Long Evans rats. A single injection of nicotine (1 mg/kg s.c.) to urethane-anesthetized time-pregnant dams at gestational day (GD) 21 increased dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid (determined by radioenzymatic assay and high-performance liquid chromatography with electrochemical detection, respectively) in male and female fetal forebrain within 30 min. No significant change was seen in norepinephrine (NE) and MOPEG, but the MOPEG/NE ratio increased in male fetuses. After the administration of nicotine by an osmotic minipump (0.25 mg/kg x hour or vehicle for controls) between GD 12 and 18/19, MOPEG was elevated at GD 18 and reduced at postnatal day (PN) 15 in both sexes; the reduction persisted in males until adulthood (2.5 months). 3,4-dihydroxyphenylacetic acid was affected by chronic drug treatment only in males with an increase at GD 18 and PN 15 and a decrease in adulthood. In contrast, homovanillic acid was reduced in adult offspring of both sexes. Male NE and dopamine of both sexes was above control level at PN 15. Cross-fostering data demonstrate that the changes were due to prenatal influences. The observations indicate that central fetal catecholamine systems are responsive to acute administration of nicotine and that chronic prenatal exposure to the drug results in persistent alterations in the functional state of these neurons. The drug-induced pattern of neurochemical alterations changes during ontogeny until adulthood; it depends upon the sex of the offspring. PMID- 2918481 TI - Stimulation of gastric alkaline secretion by histamine in rats: possible involvement of histamine H2-receptors and endogenous prostaglandins. AB - The mechanism of stimulatory action of histamine on gastric alkaline secretion was investigated in anesthetized rats. Intravenous infusion of histamine (2-8 mg/kg/hr) dose-dependently stimulated acid secretion and in the presence of omeprazole (60 mg/kg), an H+/K+-adenosine triphosphatase inhibitor, produced an increase of gastric but not duodenal alkaline secretion; the degree of gastric alkalinization was also dependent on the dose of histamine, reaching the maximal values of approximately 1.0 microEq/10 min. Cimetidine (100 mg/kg s.c.) significantly inhibited both acid and alkaline secretory responses caused by histamine, whereas indomethacin (5 mg/kg s.c.) significantly prevented the increased alkaline secretion caused by histamine as well as mucosal acidification (100 mM HCl for 10 min). Tripelennamine (10 mg/kg s.c.) had no effect on either acid or alkaline secretion. Histamine (8 mg/kg/hr) reduced the arterial blood pressure (25.3%) and increased the mucosal vascular permeability in the stomach as determined by Evans blue (160%), but these vascular responses were significantly prevented only by tripelennamine, excluding the possible contribution of the vascular effects to the increased gastric alkaline secretion. These results suggest that histamine may stimulate gastric alkaline secretion as well as acid secretion, and the mechanism of histamine-induced alkaline secretion may involve both endogenous prostaglandins and stimulation of H2-receptors. PMID- 2918482 TI - Effects of continuous infusion of cholinergic drugs on memory impairment in rats with basal forebrain lesions. AB - The effects of continuous infusion of cholinergic drugs on behavior in normal rats and on impaired acquisition and retention of several behavioral tasks in rats with basal forebrain (BF) lesions were investigated. Physostigmine and oxotremorine were infused continuously with a miniosmotic pump for 3 weeks, and the performance on several different behavioral tasks was examined during the infusion. In normal rats high doses of physostigmine (4 and 8 mg/kg/day s.c.) produced significant changes in general behavior and impaired performance in the Morris water maze. Oxotremorine (0.25-2 mg/kg/day s.c.) had no significant effects on general behavior or cognitive performance in normal rats, although severe cataracts developed at the high dose (4 mg/kg/day). A deficit in motor habituation in rats with BF lesions produced by bilateral injections of ibotenic acid (30 nmol on each side) was improved markedly by the chronic administration of physostigmine (2 mg/kg/day) and oxotremorine (1 mg/kg/day). BF lesions produced severe impairments in acquisition and retention in a passive avoidance task, an active avoidance and the Morris water maze, which was characterized by a marked disruption of retention. The impairment was also ameliorated markedly by the cholinergic drugs, whereas other behavioral impairments were not affected by the drugs. These results indicate that the continuous administration of cholinergic drugs produces a marked improvement of acquisition and retention in rats with BF lesions, and suggest that the impairment in cognitive performance, especially with regard to retention, caused by BF lesions is due to the disruption of the BF-cortical cholinergic pathway. PMID- 2918483 TI - Role of sulfhydryls in mucosal injury caused by ethanol: relation to microvascular permeability, gastric motility and cytoprotection. AB - The relationship between gastric mucosal glutathione (GSH) levels, vascular permeability, gastric motility and mucosal injury caused by ethanol was investigated in rats. Oral administration of 50% ethanol (1 ml) produced elongated reddish bands of lesions in the mucosa with a significant reduction of GSH levels and increase of microvascular permeability. These lesions were significantly inhibited by pretreatment with s.c. administered diethylmaleate (DEM: 1 ml/kg), cysteamine (100 mg/kg) and 16, 16-dimethyl prostaglandin E2 (dmPGE2, 10 micrograms/kg) but worsened markedly by N-ethylmaleimide (NEM: 10 mg/kg). Irrespective of whether the animals were treated with 50% ethanol or not, the mucosal GSH levels were significantly decreased or increased, respectively, by DEM or cysteamine, and were not affected by both NEM and dmPGE2. NEM significantly enhanced the vascular permeability in the absence or presence of ethanol (greater than 10%), whereas other agents significantly inhibited only the increased vascular permeability caused by ethanol. On the other hand, gastric motility was potently and persistently inhibited by either DEM, cysteamine or dmPGE2 at the doses which prevented ethanol-induced mucosal injury, whereas NEM had no effect on the motility. These results suggest that 1) the mucosal GSH levels do not relate directly to either development or prevention of ethanol induced gastric injury, 2) potentiation by NEM of the mucosal injury may be accounted for by its enhancement of the vascular permeability and 3) inhibition of gastric motility may be associated with prevention of mucosal lesions. PMID- 2918485 TI - Racing wheelchair crown compensation. AB - This paper is concerned with the directional stability of racing wheelchairs on crown roads. Three types of crown compensators are described and evaluated: the push-pull, the push-push, and the pull-pull. It was found that the push-push and the push-pull types of compensators have the most desirable characteristics, and were, in general, safer than the pull-pull type. In addition, the equations necessary to specify the minimum spring force required to compensate for the downhill turning moment, were derived and compared to the actual preset forces for the various compensators presently in use. It was found that the force required to maintain directional stability was less than that to deflect the crown compensator. This was due to the preference of athletes for additional stiffness needed for disturbance rejection, and to help compensate for any asymmetry in their stroke kinematics. It was also more cost-effective for the manufacturer to build stiffer-than-necessary crown compensators so that a range of individual and racing wheelchair combinations could use the same crown compensator. PMID- 2918484 TI - Mechanism of protective effects of Ca++ channel blockers on energy deprivation contracture in cultured ventricular myocytes. AB - To examine mechanisms of the protective effects of Ca++ channel blockers on energy deprivation contracture, we measured cystolic calcium ion concentration ([Ca++]i) (Indo-1 fluorescence), development of contracture (video motion detector) and ATP contents during exposure of cultured chick embryo ventricular cells to 1 mM cyanide (CN) and 20 mM 2-deoxyglucose (2-DG). The time periods required for [Ca++]i to reach 50% of [Ca++]i transient ([Ca++]i-50) and contracture were determined after exposure to 1) CN + 2-DG alone, 2) CN + 2-DG simultaneous with 1 microM verapamil (V-sim) and 3) verapamil followed by CN + 2 DG (V-pre). Time periods required to reach [Ca++]i-50 under these conditions were 4.2 +/- 0.4 min (CN + 2-DG alone), 3.8 +/- 0.4 min (NS vs. CN + 2-DG alone) (V sim) and 6.4 +/- 1.1 min (P less than .05 vs. CN + 2-DG alone) (V-pre), respectively. Time periods required for contracture development were 4.4 +/- 0.3 min (CN + 2-DG alone), 4.4 +/- 0.6 min (NS vs. CN + 2-DG alone) (V-sim) and 9.3 +/- 1.2 min (P less than .05 vs. CN + 2-DG alone) (V-pre). Three minutes after metabolic inhibition, ATP contents declined from 32.3 +/- 0.7 nmol/mg of protein to 4.2 +/- 1.0 in CN + 2-DG alone, to 4.5 +/- 0.9 (NS vs. CN + 2-DG alone) with V sim and to 8.3 +/- 2.2 (P less than .05 vs. CN + 2-DG alone) with V-pre.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918486 TI - Tests of two new polyurethane foam wheelchair tires. AB - The performance characteristics of four 24-inch wheelchair tires are considered; one pneumatic and three airless. Specifically, two new airless polyurethane foam tires (circular and tapered cross-section) were compared to both a molded polyisoprene tire and a rubber pneumatic tire. Rolling resistance, coefficient of static friction, spring rate, tire roll-off, impact absorption, wear resistance, and resistance to compression set were the characteristics considered for the basis of comparison. Although the pneumatic tire is preferred by many wheelchair users, the two new polyurethane foam tires were found to offer a performance similar to the high-pressure pneumatic tire. In addition, the foam tires are less expensive and lighter in weight than the other tires tested. PMID- 2918487 TI - Racing wheelchair rear wheel alignment. AB - This technical note describes a time-saving device for aligning the rear wheels of a racing wheelchair. The newly-developed analog alignment device is compared to the now standard discrete alignment device. The analog alignment device is found to reduce the time needed to align the rear wheels by nearly 75 percent, while increasing the accuracy of the alignment. The device does not noticeably alter the performance of the racing wheelchair and, if installed properly, the device is sufficiently resistant to fatigue. PMID- 2918488 TI - Replacing losses in kind: improved sensation following heel reconstruction using the free instep flap. AB - Two similar patients, with extensive defects of the heel treated by free tissue transfer of the contralateral instep, are discussed. Durable coverage and near normal static two-point discrimination were obtained in both. Improved results are attributed to the proximal interfascicular dissection of the medial plantar nerve and implantation into the posterior tibial nerve as the recipient. This flap may be transferred with only relatively minor donor-site complications. The contralateral instep free flap provides an ideal, durable, and sensate heel replacement, particularly when local tissues are unavailable. PMID- 2918489 TI - The importance of venous drainage in rat flaps: an experimental study. AB - Venous drainage of musculocutaneous grafts prepared on the backs of rats survived successfully by preserving the draining vein. Even in musculocutaneous flaps, venous drainage at the distal part of the flap plays an important role in a successful take. An experiment was prepared in a rat model in which the iliolumbar veins were utilized as the draining veins, and musculocutaneous flaps, 4 x 10 cm in size, were created. In this experiment, it was shown that even in random pattern musculocutaneous flaps, necrosis can be prevented by preserving the draining vein. PMID- 2918490 TI - The osteomusculocutaneous musculoperitoneal groin flap in head and neck reconstruction. AB - The anatomy of the ascending branch of the deep circumflex iliac vessels is reported. This vasculature allows the design of a musculoperitoneal flap, not exceeding 7 cm x 14 cm, together with an osteomusculocutaneous groin flap. The procedure is particularly useful, if resection of an intraoral carcinoma has included such structures as bone and the outer skin of the head and neck. The flap can be harvested with or without the internal oblique muscle. Most common composite defects after resection can be replaced by an osteomusculoperitoneal flap. Clinical applications are also described and one case report is included. PMID- 2918491 TI - Free vascularized fibular grafts. AB - Postoperative results in 21 patients with bone defects that had been treated with a free vascularized fibular graft (FVFG) were evaluated. Pathogeneses in 21 patients were bone defect or pseudarthrosis after trauma in eight, massive bone defect after resection of bone and soft tissue tumor in six, congenital pseudarthrosis of the tibia in six, and congenital arteriovenous fistula in the forearm in one patient. The follow-up ranged from 15 months to 12 years, with an average of four years and six months. At final review, 12 patients went on to primary bony union, and six additional patients obtained union following an additional conventional bone graft. Three FVFGs resulted in a non-vascularized fibular graft. However, two patients obtained union with additional bone graft. Only one patient failed to obtain bony union and eventually required an above knee amputation. Bony union rates in congenital pseudarthrosis of the tibia treated with the FVFG were lower than those in other diseases. Variables related to the surgical procedures and other factors affecting results and complications were also evaluated. PMID- 2918493 TI - Nasal alar reconstruction with an ear helix free flap. AB - Reconstruction of full-thickness defects of the nasal alae has always been a challenge. Local flaps are commonly used but often result in facial scars and bulky alae that require secondary revisions. The structural similarities between the nasal alae and auricular helices have allowed the use of free helical composite grafts to repair small nasal defects of less than 2.0 cm. Recent delineation of vascular territories of the ear has allowed the use of vascularized helical free flaps in the repair of large alar defects. Successful reconstruction of a 3.2 cm x 3.0 cm full-thickness alar defect, with a chondrocutaneous microsurgical free flap from the root of the auricular helix, is presented. The reconstruction was satisfactory as to contour, symmetry, and color match over a one year follow-up. PMID- 2918492 TI - Adipose veno-lymphatic transfer for management of post-radiation lymphedema. AB - In a patient who had post-radiation lymphedema after excision of liposarcoma, a method is described that is called adipose veno-lymphatic transfer. The technique involves transferring adipose tissue containing lymphatic vessels that surround the long saphenous vein, from the normal, healthy leg to the irradiated leg, with the creation of an arteriovenous fistula. PMID- 2918494 TI - The vascularized fascia of the scalp. AB - The fascial layers of the temporal and occipital regions of the scalp were examined in 11 fresh cadavers. In the temporal region, three independently vascularized layers were isolated, all of which could be elevated on a single superficial temporal artery, but separated to remain independently vascularized from specific branches of this parent trunk. In the occipital area, the occipital vessels could be dissected to yield a long pedicle for an independent, fascial territory that could be transposed locally or elevated as a free flap and that will, in all likelihood, carry vascularized occipital bone. Realized and as yet unrealized uses of these ultrathin vascularized tissues remain boundless. Three representative cases are presented. PMID- 2918495 TI - Late arterial thrombosis in a replanted thumb: a case report. AB - A case of arterial occlusion occurred nine years after replantation of a thumb. Factors implicated were smoking and repeated blunt trauma to the first web space. The digit was successfully revascularized after excision of a segment of thrombosed arterial vein graft. PMID- 2918496 TI - The 2-desamino and 2-desamino-2-methyl analogues of aminopterin do not inhibit dihydrofolate reductase but are potently toxic to tumor cells in culture. PMID- 2918497 TI - A carboxy-terminus truncated analogue of angiotensin II, [Sar1]angiotensin II-(1 7)-amide, provides an entry to a new class of angiotensin II antagonists. PMID- 2918498 TI - Synthesis of gastrin antagonists, analogues of the C-terminal tetrapeptide of gastrin, by introduction of a beta-homo residue. AB - A series of analogues of Boc-Trp-Leu-Asp-Phe-NH2, a potent gastrin agonist, were synthesized by introducing a beta-homo residue in the sequence. These compounds were tested in vivo on acid secretion, in the anesthetized rat, and for their ability to inhibit binding of labeled gastrin to its receptors on gastric mucosal cells. These analogues behaved as gastrin antagonists. The most potent compounds in this series were Boc-Trp-Leu-beta-homo-Asp-NHCH2C6H5 (10) (IC50 = 1 microM, ED50 = 0.2 mg/kg), Boc-Trp-Leu-beta-homo-Asp-NHCH2CH2C6H5 (11) (IC50 = 0.75 microM, ED50 = 0.5 mg/kg), Boc-Trp-Leu-beta-homo-Asp-Phe-NH2 (12) (IC50 = 1.5 microM, ED50 = 0.1 mg/kg), and Boc-Trp-Leu-beta-homo-Asp-D-Phe-NH2 (13) (IC50 = 2 microM, ED50 = 0.1 mg/kg). We could demonstrate the importance of the region of the peptide bond between leucine and aspartic acid and of the structure of the C terminal dipeptide Asp-Phe-NH2, for exhibiting biological activity on acid secretion. PMID- 2918499 TI - Fluoronaphthyridines and quinolones as antibacterial agents. 1. Synthesis and structure-activity relationships of new 1-substituted derivatives. AB - A series of novel 7-piperazinyl-1-substituted-6-fluoroquinolones and naphthyridines have been prepared and their antibacterial activities evaluated. These derivatives are characterized by having alkyl, alkenyl, arylalkyl, cycloalkyl, and cycloalkenyl groups at the 1-position. As a result of this study, derivatives 7 and 26, which are substituted with tert-butyl groups at N-1, were found to possess excellent in vitro and in vivo potency, particularly against Staphylococcus aureus, comparable to that of norfloxacin or ciprofloxacin. Structure-activity relationships of N-1 substituted alkyls and cycloalkyls are also discussed. PMID- 2918500 TI - Preparation and biodistribution of 1-[2-(3-[125I]iodo-4-aminophenyl)ethyl]-4-[3 (trifluoromethyl) phenyl]piperazine and 1-[2-(3-[125I]iodo-4-azidophenyl)ethyl]-4 [3-(trifluoromethyl)phenyl] piperazine. AB - The iodinated analogue of 1-[2-(4-aminophenyl)ethyl]-4-[3 (trifluoromethyl)phenyl]piperazine (PAPP), IPAPP (4), and the corresponding azido compound azido-IPAPP (5) were synthesized. The corresponding no-carrier-added 125I (T1/2 = 60 days, 35-60 keV) labeled compounds were also prepared. High specific binding was observed from in vitro binding studies using rat brain tissue preparation; Ki = 20 and 17.5 nM against [3H]-5-HT. In vivo biodistribution studies in rats showed that azido-[125I]IPAPP passed through intact blood-brain barrier and localized in the brain. Ex vivo autoradiography of rat brain sections exhibited a diffuse uptake pattern, which may be due to specific and nonspecific binding. The results indicate that IPAPP and azido-IPAPP may not be suitable to image the serotonin receptor in the brain. PMID- 2918501 TI - Structure-activity studies of trichothecenes: cytotoxicity of analogues and reaction products derived from T-2 toxin and neosolaniol. AB - Forty-two analogues and reaction products derived from T-2 toxin or neosolaniol were assayed for their cytotoxicity to cultured mouse lymphoma cells. Structure activity relationships confirmed the stereospecific nature of the cytotoxic action of T-2. Cytotoxicity was particularly susceptible to changes at C3, C4, C9, and C10 but was relatively unaffected by changes at C8, which appears to represent a region of steric tolerance in the interaction of T-2 with a cellular constituent. The most potent compounds were T-2, diacetoxyscirpenol, and a series of C8 ester analogues 11 and 31-35. PMID- 2918502 TI - Long acting dihydropyridine calcium antagonists. 2. 2-[2 Aminoheterocycloethoxy]methyl derivatives. AB - A series of [(2-aminoheterocycloethoxy)methyl]dihydropyridines were prepared as selective coronary vasodilators. Results showed that a wide variety of five- and six-membered heterocycles were acceptable at the 2-position of the dihydropyridine ring and in vitro potency and tissue selectivity was independent of the basicity of these heterocycles. The SAR indicated that activity was optimum when the largest ester group was placed at the 3 rather than 5 position. 2-[[2-[(3-Amino-1H-1,2,4-triazol-5-yl)amino]ethoxy]methyl]-4- (2,3 dichlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6-methyl- 1,4 dihydropyridine (3b) (UK-52,831) emerged as a potent (IC50 = 6.3 X 10(-9) M) and tissue-selective calcium channel blocker with a duration of action greater than 7 h in the anaesthetized dog. PMID- 2918503 TI - Quinazoline antifolate thymidylate synthase inhibitors: nitrogen, oxygen, sulfur, and chlorine substituents in the C2 position. AB - The synthesis of 16 new N10-propargylquinazoline antifolates with methylamino, ethylamino, (2-aminoethyl)amino, [2-(dimethylamino)ethyl]amino, (2 hydroxyethyl)amino, (carboxymethyl)amino, dimethylamino, imidazol-1-yl, methoxy, ethoxy, phenoxy, 2-methoxyethoxy, 2-hydroxyethoxy, mercapto, methylthio, and chloro substituents at C2 is described. In general, the synthetic route involved the coupling of diethyl N-[4-(prop-2-ynylamino)benzoyl]-L-glutamate (5a) with 6 (bromomethyl)-2-chloro-3,4-dihydro-4-oxoquinazoline in N,N-dimethylformamide with calcium carbonate as the base, displacement of the C2-chloro substituent with nitrogen and sulfur nucleophiles, and deprotection using mild alkali. The C2 ether analogues were most conveniently prepared by coupling 5a with 6 (bromomethyl)-2,4-diakoxy(or diphenoxy)quinazolines. In this series the final deprotection step with aqueous alkali gave simultaneous selective hydrolysis of the C4-alkoxy or C4-phenoxy substituent. The compounds were tested as inhibitors of partially purified L1210 thymidylate synthase (TS). As a measure of cytotoxicity, they were examined for their inhibition of the growth of L1210 cells in culture. The C2-methoxy analogue 11a was equivalent to the previously described tight binding TS inhibitor N10-propargyl-5,8-dideazafolic acid (CB3717, ICI 155387, 1a) against the TS enzyme and exhibited enhanced potency in culture. The C2-methoxy substituent also gave a 110-fold enhancement in aqueous solubility relative to the C2-amine. These results suggest that 11a will be an interesting compound for further study as a potential antitumor agent in vivo. A further series of 2-methoxyquinazoline antifolates with modified alkyl substituents at N10 is also described. None of these analogues equalled the activity of 11a. Thus the propargyl group appears to be the optimum N10 substituent in both 2-amino- and 2-methoxyquinazoline antifolates. PMID- 2918504 TI - 5-(1-piperazinyl)-1H-1,2,4-triazol-3-amines as antihypertensive agents. AB - A series of 5-(1-piperazinyl)-1H-1,2,4-triazol-3-amines was synthesized and screened for antihypertensive and diuretic activity in spontaneously hypertensive rats (SHR). One compound, 5-[4-[(3-chlorophenyl)methyl]-1-piperazinyl]-1H-1,2,4 triazol-3-am ine (8), was selected to define the mechanism of its antihypertensive activity. Studies in SHR suggest ganglionic blocking activity. Short-lived antihypertensive activity was observed in conscious renal hypertensive dogs. PMID- 2918505 TI - Synthesis and hypertensive activity of neuropeptide Y fragments and analogues with modified N- or C-termini or D-substitutions. AB - Porcine neuropeptide Y (NPY), NPY fragments, and analogues with D-Xaan, Ala9, D Ala9, and Met17 substitutions or modifications to the C- or N-termini were synthesized. The synthesis and purification of these peptides was achieved by using routine laboratory strategies and techniques. The ability of these peptides to alter mean arterial pressure (MAP) and heart rate (HR) in conscious rats was monitored for 15 min following intraarterial administration. Potencies and efficacies of these peptides relative to NPY were determined by comparison of dose-response curves. Administration of 40 micrograms/kg NPY resulted in a rapid, though short-lived, rise in mean arterial pressure from a basal value of 107.0 +/ 2.6 to 157 +/- 5.5 mmHg (means +/- sem, n = 13). The ED50 (+/- SE) for this response was 3.04 +/- 0.88 micrograms/kg. Peptide YY (PYY) elicited a response that was similar in magnitude but with an ED50 (+/- SE, n = 3) of 0.76 +/- 0.24 micrograms/kg while porcine pancreatic polypeptide (pPP) was inactive when tested at 40 micrograms/kg (n = 4). Relative potencies for [Ac-Tyr1]NPY, [Ac-D-Tyr1]NPY, [des-amino-Tyr1] NPY, and [Me-Tyr1]NPY ranged from 1.1 to 2.2. Potencies relative to NPY for D-substitutions at positions 2-6 and 8-13 inclusive ranged from 0.1 to 1.0. Analogues with D-substitutions at positions 1-3 exhibited an extended duration of action. Analogues with D-substitutions at positions 33-35 inclusive were inactive at 40 micrograms/kg, and [D-Tyr36]NPY was 10-fold less potent than NPY, suggesting that the integrity of the C-terminal region is critical to the overall biological action of NPY. This conclusion is supported by studies with C- and N-terminal deletion peptides. NPY2-36 showed full intrinsic activity at 40 micrograms/kg and retains 40% of the hypertensive potency of NPY. There was a sequential decrease in efficacy upon further N-terminal deletion. In contrast to the finding with NPY2-36, modification of the C-terminus either from the native carboxamide to the free carboxylic acid or by deletion of the C-terminal residue resulted in analogues which were inactive at 40 micrograms/kg. These data indicate that an essentially full-length, C-terminally amidated NPY structure is required for the hypertensive activity observed in conscious rats upon intraarterial administration of NPY and NPY analogues. PMID- 2918506 TI - Synthesis and in vitro activity of 1 beta-methyl C-2 quaternary heterocyclic alkylthio carbapenems. AB - New 1 beta-methylcarbapenems having various (substituted) quaternary heterocyclic alkythio groups at the C-2 position were synthesized and tested for antibacterial activity and renal dipeptidase susceptibility. Compounds having the 1 beta-methyl substituent were found to possess an increased stability to the enzyme. In addition, combination of the 1 beta-methyl substituent and the C-2 quaternary heterocyclic alkylthio side chain generated compounds with excellent antipseudomonal activity and improved stability toward hydrolysis by renal dipeptidase. PMID- 2918507 TI - Potential tumor- or organ-imaging agents. 29. Radioiodinated esters and amides of 20-hydroxy- and 20-aminopregn-5-en-3 beta-ols. AB - Radioiodinated benzoyl esters and amides of epimeric 20-hydroxy- and 20 aminopregn-5-en-3 beta-ols were synthesized in an effort to find an agent that would be rapidly and selectively taken up by adrenal cortical tissue. Achievement of such a goal would provide a basis for the development of adrenal imaging agents superior to those currently available for clinical use. The iodobenzoyl derivatives were obtained by treating the appropriate epimer with 2-iodobenzoic acid in the presence of dicyclohexylcarbodiimide and 4-(dimethylamino)pyridine. The resulting esters and amides were readily labeled with radioiodine by isotope exchange with sodium iodide-125 in pivalic acid. Tissue distribution studies in female rats revealed that only the esters displayed appreciable adrenal specificity, and the ester having the same configuration at C-20 as cholesterol was significantly better than the corresponding C-20 epimer. PMID- 2918508 TI - Structure-activity relationships of pyrimidine nucleosides as antiviral agents for human immunodeficiency virus type 1 in peripheral blood mononuclear cells. AB - The structure-activity relationships of several pyrimidine nucleosides related to 3'-azido-3'-deoxythymidine (AZT) were determined in human immunodeficiency virus type 1 (HIV-1) infected human peripheral blood mononuclear cells. These studies indicated that nucleosides with a 3'-azido group on the sugar ring exhibited the most potent antiviral activity. Substitution at C-5 with H, CH3, and C2H5 produced derivatives with the highest potency, whereas alkyl functions greater than C2, including bromovinyl substitution reduced the antiviral potency significantly. Changing the 3'-azido function to an amino or iodo group reduced the antiviral activity. Replacement of the uracil ring by cytosine or 5 methylcytosine produced analogues with high potency and low toxicity. Modification of the 5'-hydroxy group markedly reduced the antiviral activity. Similarly, various C-nucleoside analogues related to AZT and 2',3' dideoxycytidine were inactive and nontoxic. From these systematic studies 3' azido-2',3'-dideoxyuridine (5a), 3'-azido-5-ethyl-2',3'-dideoxyuridine (5c), and 3'-azido-2',3'-dideoxycytidine (7a) and its 5-methyl analogue (7b) were identified as potent and selective anti-HIV-1 agent in primary human lymphocytes. PMID- 2918509 TI - 1-(3-cyano-2,3-dideoxy-beta-D-erythro-pentofuranosyl)thymine (cyanothymidine): synthesis and antiviral evaluation against human immunodeficiency virus. AB - 1-(3-Cyano-2,3-dideoxy-beta-D-erythro-pentofuranosyl)thymine (cyanothymidine) (3a) has been prepared by an unambiguous route starting from D-xylose. The relative and absolute stereochemistry of 3a and its anomeric isomer 9 have been confirmed by NOE experiments and by X-ray diffraction analysis. In antiviral tests vs HIV 3a was shown to be inactive, a surprising result in view of a preliminary disclosure claiming potent anti-HIV activity. The activity previously assigned to 3a is believed to be due to contamination of that sample with the known antiviral nucleoside analogue 5b. PMID- 2918510 TI - A dihydropyridine carrier system for sustained delivery of 2',3' dideoxynucleosides to the brain. AB - The present study evaluates the utility of the dihydropyridine in equilibrium pyridinium salt redox system for the specific delivery and sustained release of a model 2',3'-dideoxynucleoside to the brain of mice as the initial effort in a search for agents that may prove effective in reversing the complicating neurological disorders of AIDS. The unsaturated nucleoside 2',3'-didehydro-2',3' dideoxythymidine (1), which is effective in protecting ATH8 cells against the cytopathogenicity of HIV-1, was converted to the corresponding N-methyl-1,4 dihydronicotinate derivative, 4, in three steps. The 5'-O-nicotinate ester, 2, obtained by reaction of 1 with nicotinyl chloride, was converted in quantitative yield to the N-methylpyridinium salt 3 on treatment with MeI in acetone. Reduction of the latter with Na2S2O4 gave 4 in 50% yield. Pseudo-first-order rate constants for the oxidation of 4 to 3 were observed in plasma (k = 3.54 x 10(-5) s-1) and in homogenates of mouse liver (k = 9.2 x 10(-5) s-1) and brain (k = 8.85 x 10(-5) s-1). None of the chemical delivery system 4 could be detected in the brain of female BDF/1 mice at 1 h postinjection. The peak level of 3 in the brain occurred at 3 h with a half-life of 25 h. Both 1 and N-methylnicotinic acid (trigonelline, 5) were readily identified by HPLC in a brain homogenate derived from mice injected (25 mg/kg) with 4. TLC showed a low level penetration of mouse brain by 1 (0.44 microgram/g wet tissue) following injection of the corresponding labeled [methyl-3H]-2',3'-unsaturated nucleoside (25 mg/kg). The data indicate that 4 crosses the blood-brain barrier to be oxidized by cerebral tissue to the ionic structure 3, which is "locked therein". The sustained local release of a 2',3'-dideoxynucleoside, such as 1, from a chemical delivery system (4) represents a potentially useful approach to the treatment of AIDS dementia complex. PMID- 2918511 TI - Antitumor and antiviral activity of synthetic alpha- and beta-ribonucleosides of certain substituted pyrimido[5,4-d]pyrimidines: a new synthetic strategy for exocyclic aminonucleosides. AB - A novel and direct synthesis of the antiviral and antitumor agent 4-amino-8-(beta D-ribofuranosylamino)pyrimido[5,4-d]pyrimidine (ARPP, 8) and its alpha-anomer (11) has been developed. Treatment of 2,4,6,8-tetrachloropyrimido[5,4 d]pyrimidine (1) with 2,3-O-isopropylidene-D-ribofuranosylamine gave an anomeric mixture of 2,4,6-trichloro-8-(2,3-O-isopropylidene-beta- and -alpha-D ribofuranosylamino)pyrimido[5,4-d]pyrimidines (3 and 4) in a ratio of 1.0:0.7. A nucleophilic displacement of the 4-chloro group of 3 and 4 with NH3 furnished 4 amino-2,6-dichloro-8-[(2,3-O-isopropylidene-beta-D-ribofuranosyl)amino ] pyrimido[5,4-d]pyrimidine (6) and its alpha-anomer (9), respectively. Catalytic hydrogenation of 6 and 9, followed by deisopropylidenation gave ARPP (8) and the alpha-anomer 11, respectively. Similarly, 3 and 4 have been transformed to 4 methoxy-8-(beta-D-ribofuranosylamino)pyrimido-[5,4-d]pyrimidine (MRPP, 14) and its alpha-anomer (17). Application of this procedure to 3 with NH2Me or NHMe2 resulted in the synthesis of 4-(methylamino)- and 4-(dimethylamino)-8-(beta-D ribofuranosylamino)pyrimido [5,4-d]pyrimidine (24 and 27, respectively). A synthesis of 8-(beta-D-ribofuranosylamino)pyrimido[5,4-d]pyrimidin-4(3H)-one (21) has also been accomplished from 3 in three steps. Selective hydrogenation of 6 furnished 4-amino-6-chloro-8-[(2,3-O-isopropylidene-beta-D-ribofuranosyl)amino] pyrimido[5,4-d]pyrimidine (36), the structure of which was established by single crystal X-ray diffraction analysis. Deisopropylidenation of 36 gave 6-chloro-ARPP (37). Extended treatment of 36 with NH3 furnished 4,6-diamino-8-[(2,3-O isopropylidene-beta-D-ribofuranosyl)amino]pyrimido [5,4-d]pyrimidine (34), which on deisopropylidenation gave 6-amino-ARPP (35). An unambiguous synthesis of 34 and 36 has also been accomplished by the reaction of 4,6,8-trichloropyrimido[5,4 d]pyrimidine (28) with 2, followed by the treatment with NH3. Nucleophilic displacement studies with 1, 6, and 28 indicated the reactivity of the halogens in these compounds is in the order of 8 greater than 4 greater than 6 greater than 2. The structures of 3 and 9 have been assigned on the basis of 1H NMR data and further confirmed by single-crystal X-ray diffraction analysis. The exocyclic aminonucleosides synthesized during this study were tested for their activity against several RNA and DNA viruses in vitro and against L1210, WI-L2, and LoVo/L in cell culture. The effect of these compounds on the de novo nucleic acid biosynthesis has been studied. Compound 14 (MRPP) exhibited enhanced activity against L1210 in vivo, when compared to ARPP (8). PMID- 2918513 TI - Crystallographic resolution and crystal and molecular structures of stereoisomers of 1,3,5-triglycidyl-s-triazinetrione. AB - The crystal and molecular structures of alpha and beta isomers of the antineoplastic alkylating agent 1,3,5-triglycidyl-s-triazinetrione (TGT) have been determined by X-ray diffraction. Although the isomers differ chemically only in the order of a carbon and an oxygen atom in one of the glycidyl epoxide rings, the molecular conformations and crystal packing arrangements are very different. The different physical and biological properties of the two stereoisomers can be explained on the basis of the structures. The sample of alpha-TGT was found to be a mixture of alpha and beta forms, and it is suggested that use of pure alpha-TGT may lead to better therapeutic results. PMID- 2918512 TI - Synthesis and evaluation of iodinated analogues of diacylglycerols as potential probes for protein kinase C. AB - Analogues of diacylglycerol containing a 3-(3-amino-2,4,6-triiodophenyl)-2 ethylpropanoyl or 3-(3-amino-2,4,6-triiodophenyl)propanoyl group in the 2 position (1a and 1b, respectively) were synthesized and shown to compete with [3H]phorbol dibutyrate [( 3H]PDBu) for binding in a crude rat brain preparation. Phorbol diesters have been shown to bind specifically to protein kinase C and the PDBu receptor has been copurified with protein kinase C activity. The four diastereomers of 1a (1c-f) were synthesized from chiral starting material and studied in the same assay. The affinities for the [3H]PDBu binding site of 1a, 1b, and two isomers of 1a with naturally occurring L configuration were comparable to that of 1-oleoyl-2-acetyl-rac-glycerol (OAG), but the D isomers of 1a were essentially inactive. The chirality of the side chain did not influence the binding affinity. Activation of protein kinase C by 1a, 1c, and 1e demonstrated the same stereochemical requirements, but none were as active as OAG. For the 1,3-isomers 2, 2a, and 2b, the competitive binding studies gave different results. The racemic mixture and the D isomer, 2b, were able to compete for binding, but the L isomer, 2a, did not compete. These studies demonstrate that diacylglycerol binding to and activation of protein kinase C is stereospecific for the glycerol backbone, but not the side chain. Furthermore, the D-1,3-isomer must exist in a conformation such that the acyl and hydroxyl oxygens assume a spatial relationship similar to that in the L-1,2-isomers. PMID- 2918514 TI - Effects of steroid D-ring modification on suicide inactivation and competitive inhibition of aromatase by analogues of androsta-1,4-diene-3,17-dione. AB - Analogues of androsta-1,4-diene-3,17-dione (3a) in which the D ring is modified were prepared and tested as suicide inactivators and competitive inhibitors of human placental aromatase. As long as the five-membered ring is intact, modifications of the D ring such as reduction or removal of the carbonyl group or conversion to a gamma-butyrolactone cause a less than 6-fold decrease in affinity for and rate of inactivation of aromatase, compared to 3a. Thus, an oxygen atom at C-17 is not required for binding of these inhibitors to aromatase, suggesting that hydrogen bonding to the D-ring oxygen does not play a major role in binding. Opening the D ring converts the cyclopentane ring to an alkyl chain and causes a greater than 300-fold decrease in affinity; this can be partially reversed by shortening the chain length. These results are consistent with a model in which the free chain of the opened D ring adopts conformations that sterically interfere with binding of the inhibitor to the enzyme. These findings may have practical applications in drug design, by allowing the preparation of 17-deoxo analogues that have high affinity for aromatase but that are not subject to reduction of the 17-carbonyl group, which is a major mode of metabolism of 3a. PMID- 2918515 TI - Alkylating partial muscarinic agonists related to oxotremorine. N-[4-[(2 haloethyl)methylamino]-2-butynyl]-5-methyl-2-pyrrolidones. AB - N-[4-[(2-Chloroethyl)methylamino]-2-butynyl]-5-methyl-2-pyrrolidone (3) and N-[4 [(2-bromoethyl)methylamino]-2-butynyl]-5-methyl-2- pyrrolidone (4) were synthesized. Compounds 3 and 4 cyclized in neutral aqueous solution to an aziridinium ion (4A). The rate constants for the cyclization of 3 and 4 at 37 degrees C were 0.025 and 0.89 min-1, respectively. The aziridinium ion was equipotent with carbachol as a muscarinic agonist on the isolated guinea pig ileum. It was more potent than the corresponding 2-pyrrolidone derivative (2A) in alkylating muscarinic receptors in homogenates of the rat cerebral cortex. This higher potency was due to greater receptor affinity of 4A as compared to 2A rather than to greater rate constant for alkylation of muscarinic receptors. These properties of 3 and 4 and their low toxicity should make them valuable tools for receptor inactivation studies in vivo and in vitro. PMID- 2918516 TI - In vitro metabolic transformations of vinblastine: oxidations catalyzed by peroxidase. AB - Vinblastine is converted to a single major metabolite during in vitro enzymatic oxidations catalyzed by horseradish peroxidase in the presence of hydrogen peroxide. Preparative-scale enzyme incubation permitted the isolation of sufficient amount of the transformation product for complete structural identification and biological evaluation. The metabolite was identified as catharinine (also known as vinamidine) by 1H and 13C NMR and by mass spectrometry. Incubations conducted in H2(18)O-enriched water gave catharinine in which a single atom of 18O was incorporated into the metabolite structure. The labeling experiment provided evidence for an unusual ring-fission pathway by which peroxidase transforms vinblastine to catharinine. Catharinine is 77 times less active than vinblastine when tested in vitro against the human T-cell leukemic cell line (CRFF-CEM). PMID- 2918517 TI - Studies on prodrugs. 10. Possible mechanism of N-dealkylation of N-masked norfloxacins having several active methylene groups. AB - As a prodrug approach to norfloxacin (NFLX, 2), we have prepared several N-masked NFLXs (1a-f) and studied the cleavage mechanism of the C-N bond of N-masked NFLXs utilizing the following experiments: (1) the oxidation of N-masked NFLXs (1a-f) with m-chloroperbenzoic acid (MCPBA) and their subsequent cleavage to 2 in chloroform at room temperature or at 50 degrees C; (2) the liberation of NFLX from N-masked NFLXs after oral administration in mice. It was found that the chemical oxidative dealkylation of N-masked NFLXs proceeded when anion stabilizing groups (e.g., CN, COR, COOR) are present on the alpha carbon of the nitrogen atom. In in vivo experiments, N-masked NFLXs having acidic hydrogens on the alpha carbon to the nitrogen atom also liberated NFLX (2) after oral administration. PMID- 2918518 TI - Heterocyclic analogues of benzamide antiarrhythmic agents. AB - A series of heterocyclic N-[(diethylamino)alkyl]arenamides related to acecainide was prepared and examined for antiarrhythmic activity. The compounds were synthesized from the corresponding known heterocyclic carboxylic acids or esters by using standard amide formation methods. The effects of the compounds on the electrophysiological properties of canine Purkinje fibers and ventricular muscle strips were determined. Most of the compounds showed effects consistent with weak class I activity. Two compounds, N-[2-(diethylamino)ethyl]-3,4,5-trimethyl-1H pyrrole-2-carboxamide and N-[2-(diethylamino)ethyl]-1H-indole-2-carboxamide, displayed prolongation of the action potential duration and functional refractory period indicative of modest class III electrophysiological activity. Representative compounds were examined by using molecular modeling techniques. Compounds of differing activity classes displayed qualitatively different electrostatic potential maps. PMID- 2918519 TI - Preparation and antitumor activity of additional mitomycin A analogues. AB - On the basis of qualitative structure-activity relationships developed in the preceding article, a series of 32 new mitomycin A analogues were prepared and tested in antitumor screens. Seven of them gave greater prolongation of life (ILS) than mitomycin C in the mouse P388 leukemia assay. They included examples with 7-O substituents such as cyclic ethers and nitrogen heterocycles. A Hansch analysis was attempted with log P and MR as the independent variables, but no statistically significant correlation could be made. Seven compounds, chosen mainly for their good potency (MED), were tested in the subcutaneous B16 melanoma assay in mice and four of them showed greater ILS than mitomycin C. PMID- 2918520 TI - (6R,6S)-5,8,10-trideaza-5,6,7,8-tetrahydrofolate and 6(R,6S)-5,8,10-trideaza 5,6,7,8-tetrahydropteroyl-L-ornithine as potential antifolates and antitumor agents. AB - (6R,6S)-5,8,10-Trideaza-5,6,7,8-tetrahydropteroic acid was synthesized in several steps from 4,4-(ethylenedioxy)-cyclohexanone and [4-(tert butyloxycarbonyl)benzyl]triphenylphosphonium bromide and was elaborated to (6R,6S)-5,8,10-trideaza-5,6,7,8-tetrahydropteroyl-L-glutamic acid and (6R,6S) 5,8,10-trideaza-5,6,7,8-tetrahydropteroyl-L-ornithin e. Compound 1 was found to be a good substrate for partially purified mouse liver folypolyglutamate synthetase (FPGS), with a Michaelis constant (Km = 15 microM) comparable to that reported for the reduced folate substrate (6S)-5,6,7,8-tetrahydropteroyl-L glutamic acid and for (6R,6S)-5,10-dideaza-5,6,7,8-tetrahydropteroyl-L-glutamic acid (DDATHF). However, in striking contrast to DDATHF, which is potently cytotoxic, 1 failed to inhibit tumor cell growth in culture at concentrations of up to 100 microM. These results suggested that the NH at position 8 of DDATHF is important for cytotoxic activity but not for polyglutamylation. Just as 1 was a good substrate for FPGS, the ornithine analogue 2 proved to be among the more potent competitive inhibitors of this enzyme discovered to date, with a Ki,s of 10 microM. While the binding affinity of 2 was lower than that reported for 5,6,7,8-tetrahydropteroyl-L-ornithine (H4PteOrn), very substantial FPGS inhibition was observed even though N5,N8, and N10 in H4PteOrn were replaced by carbon. Binding to FPGS thus appears to be tolerant of bioisosteric replacements made simultaneously in ring B and the bridge region. Neither 1 nor 2 was active in preventing cell growth in culture at concentrations of up 100 microM. The N delta-hemiphthaloyl derivative of 2, synthesized as a potential prodrug, was also inactive. PMID- 2918521 TI - Evaluation of glycolamide esters and various other esters of aspirin as true aspirin prodrugs. AB - A series of glycolamide, glycolate, (acyloxy)methyl, alkyl, and aryl esters of acetylsalicylic acid (aspirin) were synthesized and evaluated as potential prodrug forms of aspirin. N,N-Disubstituted glycolamide esters were found to be rapidly hydrolyzed in human plasma, resulting in the formation of aspirin as well as the corresponding salicylate esters. These in turn hydrolyzed rapidly to salicylic acid. The largest amount of aspirin formed from the esters were 50 and 55% in case of the N,N-dimethyl- and N,N-diethylglycolamide esters, respectively. Similar results were obtained in blood with the N,N-dimethyl- and N,N diethylglycolamide esters. Unsubstituted and monosubstituted glycolamide esters as well as most other esters previously suggested to be aspirin prodrugs were shown to hydrolyze exclusively to the corresponding salicylic acid esters. Lipophilicity parameters and water solubilities of the esters were determined, and structural factors favoring ester prodrug hydrolysis at the expense of deacetylation to yield salicylate ester are discussed. The properties of some N,N disubstituted glycolamide esters of aspirin are highlighted with respect to their use as potential aspirin prodrugs. PMID- 2918522 TI - Possibilities and limitation of prenatal diagnosis and carrier determination for Duchenne and Becker muscular dystrophy using cDNA probes. AB - Two cDNA probes, cf23a and cf56a, identify deletions of selected exons in about 50% of our DMD/BMD patients. We have estimated the most likely order of the 11 exons detectable with both probes with respect to the different extensions of the deletions. In one of our BMD pedigrees, the observed deletion could be traced in the affected males through three generations. This result shows that with the use of cDNA probes detecting deletions, the only risk of error in genomic prenatal diagnosis is the general high frequency of new mutations for DMD/BMD. This is important progress in diagnosis compared to the 2 to 5% risk of misdiagnosis because of crossing over events using conventional linkage analysis with bridging or intragenic probes. The first prenatal diagnosis of an unaffected fetus of a woman who is a DMD carrier according to ultrasound examination is described. In one of our DMD males, the cDNA probe cf56a detects a deletion breakpoint. His sister also shows the altered band and is therefore a DMD carrier, while his mother has a totally normal band pattern. The interpretation of this observation could be either germline mosaicism or two identical new mutations. The identification of deletion breakpoints is a new diagnostic strategy, especially for carrier determination, which excludes misdiagnosis owing to crossing over events and the problems of dosage estimation. It is, however, limited by the low frequency of breakpoints detectable with cDNA probes. Therefore, the generation of new intron probes in this region is an important goal. PMID- 2918523 TI - Genetic aspects of tuberous sclerosis in the west of Scotland. AB - Complete ascertainment of tuberous sclerosis was attempted in the west of Scotland (population 2,763,000). A total of 101 patients was identified, giving an overall minimum prevalence of 1 in 27,000, but for children under 10 years of age the minimum prevalence was 1 in 12,000. Both parents of 84 of the ascertained cases were assessed for signs of tuberous sclerosis. In 51 pairs of parents no evidence of the condition was seen, indicating that up to 60% of the cases were new mutations. The mutation rate was estimated at 2.5 X 10(-5) mutations per gene per generation. Analysis of parental ages for the new mutations did not show a significant age effect. Thirty-five patients occurred in 13 families containing other affected subjects. The pattern of inheritance was consistent with an autosomal dominant trait in these families. In one sibship, non-penetrance or gonadal mosaicism resulted in affected sibs with normal parents. Of two further sibships where non-penetrance was suspected, one was shown to represent a single new mutation in monozygotic twins and the other to involve non-paternity. PMID- 2918524 TI - The use of low density lipoprotein receptor activity of lymphocytes to determine the prevalence of familial hypercholesterolaemia in a rural South African community. AB - The diagnosis of heterozygous familial hypercholesterolaemia in three rural South African communities in which hypercholesterolaemia is very prevalent could be confirmed by the measurement of low density lipoprotein (LDL) receptor activity in circulating lymphocytes. A nominal cut off point could be proposed which separated the LDL receptor activity of 24 clinically diagnosed heterozygous FH patients and 31 healthy people. LDL receptor activity was measured as total degradation of 125I-LDL and expressed as ng LDL/mg cell protein/6 hours. The cut off point was set at 970 ng/mg protein/6 hours. This proposed cut off point was tested by assaying the LDL receptor of three homozygous FH patients and seven of their obligate heterozygous FH first degree relatives. The three homozygous FH patients showed no receptor activity and the activity of the seven obligate heterozygous first degree relatives fell below the proposed cut off point. To determine the prevalence of FH in the study population, all persons aged 15 to 24 years whose total cholesterol levels fell above the 80th centile for their age and sex, as well as their families, were approached (n = 114). The LDL receptor activity in lymphocytes of 77 of these persons aged 15 to 24 years was determined after applying the exclusion criteria. Ten of the 77 participants had LDL receptor activity below 970 ng LDL/mg protein/6 hours and were therefore diagnosed as being heterozygous FH patients. The calculation of the prevalence (corrected for exclusions) revealed that one in 71 of the 15 to 24 year old permanent residents in the predominantly Afrikaans speaking community suffered from heterozygous FH. This is higher than any FH prevalence previously reported for any group. PMID- 2918525 TI - Congenital hypothyroidism, spiky hair, and cleft palate. AB - Two brothers are described with athyroidal hypothyroidism, spiky hair, choanal atresia, cleft palate, and bifid epiglottis. Polyhydramnios was present in the third trimester of each pregnancy. These abnormalities appear to represent a new syndrome. PMID- 2918526 TI - Hydrocephalus, tall stature, joint laxity, and kyphoscoliosis: a new inherited disorder of connective tissue? AB - We describe two sisters with hydrocephalus, tall stature, joint laxity, and thoracolumbar kyphosis. PMID- 2918527 TI - Further delineation of the Yunis-Varon syndrome. AB - A boy with intrauterine growth retardation, microcephaly, dysostosis of the skull, hypoplastic facial bones, labiogingival retraction, agenesis of the clavicles, distal aphalangia, and severely hypoplastic thumbs and halluces is described. The features are consistent with the Yunis-Varon syndrome. Review of published reports shows this to be a generalised disorder with variable manifestations in the skeletal, ectodermal, and cardiovascular systems. The consanguinity of the parents of the present case is in agreement with autosomal recessive inheritance. PMID- 2918528 TI - A case of interstitial deletion of 10q25.2----q26.1. AB - A de novo interstitial deletion of chromosome 10, del(10)(pter----q25.2::q26.1--- qter), was detected in a newborn female with facial anomalies, failure to thrive, and subsequent developmental delay. This case is compared with 10 previous reports of monosomy 10q within the q25----qter region. PMID- 2918529 TI - Obesity and abnormal behaviour associated with interstitial deletion of chromosome 18 (q12.2q21.1). PMID- 2918530 TI - Partial trisomy 16q secondary to a maternal 9;16 translocation. PMID- 2918531 TI - Duplication 6p and deletion 9p. PMID- 2918532 TI - The megacystis-microcolon-intestinal hypoperistalsis syndrome: a fatal autosomal recessive condition. AB - We report the cases of two sibs with the megacystis-microcolon-intestinal hypoperistalsis syndrome. The parents are first cousins. These cases further support the view that this syndrome is inherited in an autosomal recessive fashion. PMID- 2918533 TI - Apple peel syndrome in sibs. AB - We report an Arab sibship of two brothers with apple peel jejunal atresia. The parents are consanguineous. Other reported familial cases are briefly reviewed. PMID- 2918534 TI - Iris coloboma, ptosis, hypertelorism, and mental retardation. PMID- 2918535 TI - Teratogenicity of ergotamine. PMID- 2918536 TI - Interstitial deletion of distal 13q associated with Hirschsprung's disease. AB - Three cases of interstitial deletion of chromosome 13 involving the common segment 13q22.1----q32.1 are reported. In addition to the recognised clinical features of this deletion, two had Hirschsprung's disease. PMID- 2918537 TI - Hereditary distal muscular atrophy with vocal cord paralysis and sensorineural hearing loss: a dominant form of spinal muscular atrophy? AB - In 1980 Young and Harper described a family with an unusual form of distal spinal muscular atrophy associated with vocal cord paralysis. We report a family with three similarly affected subjects. Progressive sensorineural hearing loss was an additional feature in our patients. Electrophysiological and histological investigations did not exclude an involvement of sensory neurones. Whether the classification of this dominant disorder with the spinal muscular atrophies is justified will depend on additional studies in further families. PMID- 2918538 TI - Knowledge and perceptions of haemoglobinopathy carrier screening among general practitioners in Cardiff. AB - A questionnaire was sent to 164 principal general practitioners working in Cardiff. A response rate of 81% was achieved. A total of 70% of respondents had had professional contact with a carrier for thalassaemia and a similar number for sickle cell disease, while 57% had recommended that a patient should be screened for haemoglobinopathy status. GPs tended to underestimate greatly the prevalence of haemoglobinopathies in South Glamorgan, and were uncertain of the ethnic minorities that were at particular risk. A carrier screening programme was considered justified by the majority of GPs in Cardiff and reasons for this opinion were examined. However, before a screening programme is started, information on whom to screen and their relative risk needs to be made more widely available. PMID- 2918539 TI - Rhodanese isozymes in three subjects with Leber's optic neuropathy. AB - Previous studies have reported an association between Leber's optic neuropathy and deficiency of rhodanese activity in liver and rectal mucosa. We have studied the rhodanese isozymes in liver biopsies from three subjects with Leber's optic neuropathy. The rhodanese isozyme patterns were indistinguishable from controls both in relative intensity and position on the isoelectric focusing pH gradient. No new rhodanese isozymes were observed and there was no evidence of deficiency in any of the cases. PMID- 2918540 TI - Stickler's syndrome. PMID- 2918541 TI - Interstitial deletion of the long arm of chromosome 2 with normal levels of isocitrate dehydrogenase. AB - We report a 16 year old boy with the abnormal karyotype 46,XY,del(2)(q32.2q33.1) who has mental retardation, microcephaly, epilepsy, craniofacial dysmorphism, distinctive scalloped skin pigmentation, and normal levels of isocitrate dehydrogenase. PMID- 2918542 TI - A terminal deletion (14)(q31.1) in a child with microcephaly, narrow palate, gingival hypertrophy, protuberant ears, and mild mental retardation. AB - A female child with a terminal deletion on the long arm of chromosome 14, 46,XX,del(14)(q31.1), presented with microcephaly, narrow palate, gingival hypertrophy, protuberant ears, and a small haemangioma on the back. She was mildly mentally retarded. Only a few patients with a partial deletion of 14q (14q ) have been reported without consistent clinical findings. Although a clinical syndrome associated with ring chromosome 14, r(14), has been established, no distinct pattern has been so far reported in 14q-. PMID- 2918543 TI - Familial distal trisomy 8(q24.13----qter). AB - Trisomy for the distal part of the long arm of chromosome 8(q24.13----qter) is described in three sibs. The anomaly arose as an adjacent 1 meiotic segregation from a balanced reciprocal translocation t(1;8)(q44; q24.13)mat. PMID- 2918544 TI - Is there an autosomal recessive form of the split hand and split foot malformation? AB - A family is described in which four subjects in two sibships had typical split hand/foot malformation. The possibility of the existence of a rare autosomal recessive form of the malformation is discussed, as well as a two locus model. In the two locus model the dominant mutation leading to the split hand/foot malformation is controlled by a gene at another locus. A dominant mutation at the controlling locus leads to non-penetrance of the split hand/foot mutation. PMID- 2918545 TI - The association of Angelman's syndrome with deletions within 15q11-13. AB - The inheritance of Angelman's syndrome, a disorder characterised by mental retardation, epilepsy, ataxia, and a happy disposition, is debated because affected sibs occur less frequently than expected with autosomal recessive inheritance. After discovering two unrelated patients with a small deletion of the proximal long arm of chromosome 15, 10 further patients with Angelman's syndrome were reassessed. Five had apparently normal karyotypes, four had a deletion within 15q11-13, and one had a pericentric inversion, inv(15)(p11q13) involving the same chromosomal region. In the latter case, the healthy mother had the same pericentric inversion, indicating that the patient also had a submicroscopic mutation on his other chromosome 15. These data map the Angelman locus to 15q11-13 and suggest that de novo visible deletions (associated with a low recurrence risk) and autosomal recessively inherited cases combine to give an overall sib recurrence risk of less than 25%. PMID- 2918546 TI - Familial supravalvular aortic stenosis: a genetic study. AB - Supravalvular aortic stenosis (McKusick 18550) is a rare hereditary condition with autosomal dominant transmission. However, the available data have been limited to small family groups which do not allow the definition of the degree of penetrance of the disease. The present study describes a large family with a high frequency of supravalvular aortic stenosis including five generations and 80 subjects, the largest family group with this disease studied so far. The study was carried out prospectively in 66 subjects (clinical examination, ECG, M mode and two dimensional echocardiography). In 14 subjects available data were examined retrospectively. In 10 patients cardiac catheterisation was performed (prospective study in eight). The disease was present in 36 (45%) of the 80 subjects investigated, on the basis of clinical, echocardiographic, and haemodynamic (when available) criteria. The disease was found to be severe in eight cases (22%), moderate in six cases (17%), mild in 13 (36%), and undefined in eight (22%) patients. In one case (3%), multiple pulmonary stenoses were noted in the absence of supravalvular aortic stenosis. Genetic analysis of these data shows, for the first time, the degree of penetrance of the supravalvular aortic stenosis trait (K = 0.86) and confirms that it is transmitted with incomplete penetrance and variable expressivity. PMID- 2918547 TI - Spondyloenchondrodysplasia. AB - Spondyloenchondrodysplasia is a rare autosomal recessive skeletal dysplasia with vertebral dysplasia and enchondroma-like lesions in the pelvis and long bones. The vertebral bodies show dorsally accentuated platyspondyly with disturbance of ossification. Clinical abnormalities such as short stature, rhizomelic micromelia, increased lumbar lordosis, barrel chest, facial anomalies, and clumsy movements may be present. We report on four patients, three of them from one family, who showed a wide range of clinical and radiological changes to document considerable variability of expression of the mutated gene. PMID- 2918548 TI - Lung cancer and smoking: the science of applying preventive strategies. PMID- 2918549 TI - Summary of Institute of Medicine study of resources for clinical investigation. PMID- 2918550 TI - Binding kinetics of tetrachloro-1,2-diaminocyclohexaneplatinum (IV) (tetraplatin) and cis-diamminedichloroplatinum (II) at 37 degrees C with human plasma proteins and with bovine serum albumin. Does aquation precede protein binding? AB - Experiments were conducted at 37 degrees C to study the kinetics of (a) binding of cis-diamminedichloroplatinum (II) (CDDP) and of a racemic mixture of d- and l isomers of trans-tetrachloro-1,2-diaminocyclohexaneplatinum (IV) [or tetraplatin (TP)] to protein [human plasma proteins or bovine serum albumin (BSA)]; (b) aquation (acid hydrolysis) of CDDP and of TP; and (c) binding of charged (aquated) CDDP species to BSA. The experiments were performed at clinically relevant concentrations for CDDP, so that the proportional concentrations of platinum complexes relative to the concentrations of other chemical species in blood plasma were similar to those obtaining in the clinical use of the drug. "Free" (unbound) platinum complexes were separated from the protein-bound complexes were separated from the protein-bound complexes by gel filtration chromatography. By use of ion-exchange chromatography, charged platinum species were separated from the uncharged species and free charged platinum species of CDDP were separated from those bound to BSA. Platinum in various fractions was quantitated by atomic absorption spectrophotometry with electrothermal atomization; proteins were quantitated by te Bradford method with Coomassie blue dye. The kinetic data obtained by the application of these methods for CDDP are in good agreement with those obtained by other methods, e.g., binding rates based on separations by centrigugal ultrafiltration. The overall protein-binding reaction of CDDP was consistent with a binding process comprising two consecutive first-order reaction steps: the rate-controlling aquation reaction [half-life (t 1/2), approximately 2 hr] followed by a more rapid binding reaction of the charged (aquated) CDDP species to the protein (t 1/2, approximately 23 min). However, the results for TP indicated that prior aquation was not required for protein binding, and we could surmise that binding of TP to protein proceeds via a direct nucleophilic attack. An unexpected finding was the marked, reproducible difference in rates of aquation between the two lots of TP that we used; this finding suggests the need for cautions evaluation of pharmacokinetic data describing the behavior of TP. PMID- 2918551 TI - Cytotoxicity of receptor-mediated 16 alpha-[125I]iodoestradiol in cultured MCF-7 human breast cancer cells. AB - Therapeutic strategies using 125I-labeled steroid hormones are attractive in light of the estrogen dependence of many human breast cancers and the favorable microdosimetry resulting from 125I decay. We determined the uptake, specific estrogen receptor (ER) binding, and cytotoxicity of 16 alpha-[125I]iodoestradiol in cultured MCF-7 human breast cancer cells. The cytotoxicity of receptor mediated 125I appears to be sufficient in MCF-7 cells to warrant in vivo experimentation. Furthermore, cytotoxicity not specific to ERs is minimal within the dose range necessary for ER saturation and specific cell killing. Competitive toxicity studies using nonradioactive 17 beta-estradiol demonstrate an unequivocal relationship between ER binding and clonogenic viability. PMID- 2918552 TI - Inhibition of metastases of a human melanoma xenograft by monoclonal antibody to the GD2/GD3 gangliosides. AB - A human melanoma variant cell line was obtained from a lung metastasis that arose spontaneously after we inoculated melanoma cells sc into a nude mouse. In this model, IgG2a monoclonal antibody (MAb) ME 36.1 defining the GD2/GD3 gangliosides inhibited melanoma growth at the primary site and metastatic spread of the cells, whereas an IgG1 variant of MAb ME 36.1 inhibited lung metastasis formation only. Possible mechanisms of antitumor effects of MAb ME 36.1 are discussed. PMID- 2918554 TI - Cancer sweepstakes. PMID- 2918555 TI - Predicting the outcome of exploratory laparotomy in ICU patients with sepsis or organ failure. AB - Critically ill patients with sepsis and/or organ failure are difficult to assess. They are often comatose or on steroids and many nonspecific findings such as fever, positive blood cultures, or septic shock which may suggest intra-abdominal sepsis are far from diagnostic. To determine whether decision making regarding the use of laparotomy in these patients could be improved upon, we reviewed our experience with consecutive intensive care unit patients who had laparotomy and we related laparotomy outcome to clinical signs and symptoms. Seventy-three per cent of the 100 laparotomies reviewed were positive for intra-abdominal sepsis. A discriminant function analysis revealed that eight factors in combination predicted laparotomy outcome. However, the overall accuracy of the discriminant function prediction (76.8%) offered little improvement over the policy in place for performing laparotomies in this group of patients at the participating hospitals during the time period of our investigation. PMID- 2918553 TI - Transfected mouse melanoma lines that express various levels of human melanoma associated antigen p97. AB - The gene for the human melanoma-associated antigen p97 has been introduced by cDNA transfection into cells from clone M2 of the K1735 mouse melanoma, which metastasizes to the lung when injected iv into syngeneic C3H/HeN mice. Tumor clones were established from the transfected cells and found to differ in the level of p97 expression. Their outgrowth in immunocompetent syngeneic mice was shown to inversely correlate with p97 antigen expression, and lines that express higher p97 levels elicited a stronger delayed-type hypersensitivity response when injected into the footpads of mice immune to p97. Five clones which expressed very high levels of p97 failed to grow in immunocompetent C3H/HeN mice while they formed tumors in nude (nu/nu) mice. The highest expressing clone, 2A, grew slightly faster than any of the other clones when cultured in vitro. Since several of the transfected clones were found to express a stable level of p97 and have consistent in vivo growth behavior, they provide a useful model for various forms of antigen-specific active and passive immunotherapy with the same agents as those intended for human application. PMID- 2918557 TI - Longitudinal evaluation of left ventricular performance in dogs following nonpenetrating cardiac trauma. AB - To investigate the temporal changes of global left ventricular function following nonpenetrating cardiac impact, studies were performed in ten purpose-bred dogs. Under full anesthesia and after hemodynamic and angiographic measurement, a midline thoracotomy was performed and a 12 m/sec blunt impact was delivered to the anterior surface of the heart in eight dogs with an air-pressurized impactor. Two dogs were sham operated and did not undergo trauma. After closing the chest, the hemodynamic measurements were repeated at 3 hours, 3 days, 2 weeks, and 5 weeks after impact. Hemodynamic measurements included left ventricular end diastolic pressure and peak left ventricular positive and negative rates of change of pressure. Left ventricular ejection fraction was calculated from ventriculograms obtained with the dog positioned on its right side. All indices of left ventricular performance in dogs that underwent trauma were depressed at 3 hours after impact and recovered gradually to near normal levels at 2 to 5 weeks after trauma. Recovery of left ventricular function occurred in spite of residual patchy scarring of the left ventricular myocardium in the region of impact. No variability of left ventricular function indices was observed over the course of the study in the two sham-operated dogs. The results indicate that blunt cardiac impact can cause depression of left ventricular performance in the immediate post impact period, but near complete recovery of function occurs within 2 to 5 weeks after the injury, in spite of residual scarring. PMID- 2918556 TI - Cerebral function monitoring in rats with a critical hepatic injury treated with pneumatic antishock garment and infusion. AB - Twenty-nine rats were subjected to a severe standardized hepatic injury and divided into four groups. In addition to controls, the animals were treated with PASG inflated to 40 mm Hg, PASG and infusion of Ringer's acetate, or PASG and infusion of Ringer's acetate and Dextran 70 in combination. The aim of the infusion therapy was to stabilize the mean aortic blood pressure at 60 mm Hg. PASG significantly prolonged the survival time and the time during which a sensory evoked response could be observed. The PASG also prolonged the time before the EEG amplitude began to decrease or a burst-suppression pattern appeared in the EEG. Intravenous infusion of Ringer's acetate did not prolong these times compared to when PASG was used alone; when Dextran 70 was added to the infusion therapy these times were reduced. Changes in the EEG were recorded at a mean aortic pressure of 60 mm Hg when infusions were given, whereas the aortic pressure had to fall to 40 mm Hg before any changes could be observed when no infusions were used. PMID- 2918558 TI - Production and release of C3 by cultured monocytes/macrophages isolated from burned, trauma, and septic patients. AB - The release of C3 under various conditions by cultured monocytes/macrophages isolated from burned, trauma, and septic trauma patients was determined. When monocytes were cultured for up to 14 days there was no difference in production and release of C3 by normals and patients; C3 production rose slowly at first then rose rapidly from 8-14 days of culture. C3 production continued for up to 28 days of culture. When lymphocytes were present with the monocytes for the first 24 hr of culture there were differences in C3 production by normal and patient cells at various times of culture. There were differences in C3 release by patients' 24 hour-cultured cells at certain postburn and injury days. Macrophages from burned patients released less C3 than normal cells and macrophages from septic trauma patients released more C3 than normal cells. PMID- 2918559 TI - Analysis of life expectancy and living status of elderly patients surviving a burn injury. AB - This study evaluates the long-term outcome of elderly patients discharged from hospital after a burn injury. Ninety-three patients over the age of 60 years, admitted to a regional burn center, were included in the study from January 1981 to January 1986. The in-hospital mortality rate was 49.4%. Patients' living status was graded according to dependency: 47% of patients were reduced to a more dependent living status on discharge, and 36% of the survivors were followed up for between 1 and 5 years. During this time seven (19.4%) patients died, three (8.3%) became more independent, four (11.1%) less independent. Life table analysis of discharged patients showed no accelerated death rate in comparison with the normal population. The high mortality associated with burns in the elderly was confirmed. Half the survivors were at least temporarily less independent. Projected life expectancy for the elderly surviving a burn is comparable with his/her uninjured counterpart. PMID- 2918560 TI - Advanced three-dimensional evaluation of acetabular trauma: volumetric image processing. AB - Volumetric image processing is a new approach to generating simulated three dimensional images from transaxial CT data. The major advantages compared to conventional surface-rendering 3D technique include: preservation of every pixel of CT data for increased accuracy of rendered image; tissue layer translucency allowing appreciation of multiple tissue layers on each image; simulation of real time rotation in varying axes for optimal appreciation of abnormalities; and a high-speed, high-capacity computer setup which generates high-quality images rapidly, giving the system sufficient flexibility for these complicated functions while remaining user friendly and fast. PMID- 2918561 TI - Non-cavitary hemorrhage producing shock in trauma patients: incidence and severity. AB - Intraperitoneal and intrathoracic bleeding, cavitary hemorrhage (CH), are recognized as major causes of hypovolemic shock in trauma patients. Blood loss from fractures and lacerations, non-cavitary hemorrhage (NCH), is not considered a common cause of shock. Of 466 trauma patients admitted during a 12-month period without spinal cord injury, burns, or ongoing CPR, 13.1% were admitted in hypovolemic shock. Of these 466 patients 55.7% had strictly non-cavitary sources of blood loss, most commonly long bone fractures and skin lacerations. There was no significant difference in the resuscitative fluid requirements, morbidity, or mortality between patients presenting in hypovolemic shock due to CH and NCH. Blood loss from NCH must be recognized as a significant source of hypovolemic shock in trauma patients. PMID- 2918562 TI - Injuries to the hand inflicted by rotary snowcutters. AB - In the period January 1, 1975, through December 31, 1986, 28 patients were treated for hand injuries caused by small home rotary snowcutters. These injuries were characterized by extensive lacerations and contusions, particularly on the dorsal side of the hand and the fingers, with concomitant extensor tendon ruptures, comminuted and complicated fractures, and traumatic amputations of fingers of the dominant hand. The index and middle finger were nearly always injured; the thumb was usually totally spared. The frequency of postoperative complications was low after delayed primary surgical treatment. In this series the mean permanent medical disablement was found to be 12%, ranging from 0 to 50%. The present observations, when made available, alarmed national authorities. In turn, manufacturers were required to equip rotary snowcutters with motorquenchers. This device will probably effectively prevent these injuries in the future. PMID- 2918563 TI - Snowblower injuries to the hand. AB - When operated carelessly, snowblowers can produce serious trauma to the hand. During a 3-year period, 13 cases were identified. The injuries occurred when the operators attempted to dislodge impacted snow from the snowblower chute. Experience with the equipment did not appear to be a factor. The frequency of injuries was directly related to the depth of snowfall. Higher temperatures and wet snow were also important. The long and ring fingers of the dominant hand were most frequently injured. A total of 22 digits in 13 patients were involved. Three digits underwent amputation. All patients had fractures, ranging from simple closed fractures of the distal tuft to open comminuted fractures of the proximal phalanx. Injuries were treated with debridement and primary repair. Operator carelessness is usually responsible for the injury. If the public is made aware of snowblower hazards at the time of heavy snowfall, injuries may be avoided. PMID- 2918564 TI - Blunt chest trauma in the elderly. AB - Significant differences were identified between a group of elderly patients (65 years and older) and a nonelderly group both with blunt thoracic trauma. There was a lower incidence of elderly patients presenting in shock; however, cardiopulmonary arrest at arrival was more frequent in this group. Although the types of complications were similar in both populations, the morbidity and mortality rates were higher in the elderly. A high index of suspicion must be generated for an elderly patient who has sustained blunt chest trauma. An aggressive diagnostic and therapeutic approach may lead to a decrease in the high morbidity and mortality rates in the elderly. PMID- 2918566 TI - Pediatric equestrian injuries: a 14-year review. PMID- 2918565 TI - Management of acute head injuries in a Norwegian county--effects of introducing CT scanning in a local hospital. AB - Introducing a new diagnostic tool, a CT scanner, in a county hospital resulted in a marked redistribution of the handling of acute/severe head injuries. Before the introduction of the CT scanner, a substantial number of these patients were referred to the regional neurosurgical unit. After having acquired its own scanner, the county hospital took over most of the diagnostic and therapeutic tasks concerning acute head injuries, surgery inclusive. This change in policy resulted in more patients surviving without sequelae, and reduced the average latency to surgery. The proportion of operated patients increased considerably, from 23% to 64%. In a relatively large proportion of the patients, there were complications with continuous ICP monitoring using the subdural bolt. This procedure was therefore discontinued. In spite of the improved results caused by the observed redistribution, the study indicates a need for additional training of the county hospital staff. PMID- 2918567 TI - Traumatic avulsion of arch vessels in a child: primary repair using hypothermic circulatory arrest (case report). AB - We present here the case of a 7-year-old girl who was ejected from a speeding motor vehicle and suffered avulsion of the left carotid and left subclavian arteries. Repair was affected primarily without the need of graft material, using cerebral protection of cardiopulmonary bypass, profound hypothermia, and circulatory arrest. PMID- 2918568 TI - Traumatic aortocaval fistula: case report. AB - A gunshot wound to the right chest in a 21-year-old female resulted in an acute aortocaval fistula at the level of the diaphragm. An operative approach planned for maximal exposure, vascular control with intraluminal balloon catheters, and conservation of blood with an intraoperative autotransfusion system resulted in successful repair and long-term survival. PMID- 2918569 TI - Traumatic hemoperitoneum due to a Meckel's mesodiverticular band: case report. AB - The blood supply to a Meckel's diverticulum exists either within the small bowel mesentery, or within a separate mesodiverticular band. The latter is associated with bowel obstruction. It is a rare source of hemorrhage. The case report describes hemoperitoneum resulting from blunt trauma-induced disruption of a mesodiverticular band. PMID- 2918570 TI - Snow blower injuries to the hand. PMID- 2918571 TI - Shotgun wound ballistics. PMID- 2918572 TI - Frequencies of hepatitis B, delta and human immune deficiency virus markers in multitransfused Saudi patients with thalassaemia and sickle-cell disease. AB - Frequencies of hepatitis B, delta and human immune deficiency virus markers were investigated in multitransfused thalassaemic (212) and sickle-cell disease (173) patients from four different regions of Saudi Arabia. Irrespective of the region, thalassaemics had higher exposure rate to HBV (14.7-31.6% HBsAg; 79.4-97.9% all markers) than sickle-cell disease patients (9.4-27.5% HBsAg; 45.3-85% all markers) and controls (5.8-21.3% HBsAg; 30.8-72.5% all markers). Evidence of delta infection was found in thalassaemics from all regions (7.1-21.0%); also, the prevalence of anti-delta was higher in thalassaemics than in sickle-cell disease patients and controls. Only five thalassaemics were positive for antibody to the human immune deficiency virus (HIV). In the light of these results, screening of all donated blood for HBsAg and for anti-HIV by the most sensitive techniques is essential. Furthermore, early vaccination of Saudi children with thalassaemia and sickle-cell disease against HBV is recommended. PMID- 2918573 TI - Evaluation of a sanitation programme using eggs of Ascaris lumbricoides in household yard soils as indicators. AB - Soil samples were analysed for the presence of Ascaris lumbricoides eggs as indicators of environmental pollution in household yards in Maputo, Mozambique, with the objective of evaluating the impact of a programme for the promotion of improved latrine construction. The locations for soil sample collection were defined by a random grid on which household activities were mapped. In addition, parasitological examinations were carried out amongst household residents. No significant difference was found between the type of latrine in use and the presence of Ascaris eggs in the soil or human Ascaris infection. Households with at least one infected person appeared more likely to have Ascaris eggs in the yard. It was notable that egg counts around the latrines were only slightly greater than in other areas of the yard and less than those immediately in front of the dwelling. This is taken to indicate that faecal pollution of the household environment is due more to promiscuous defecation than to poor construction or maintenance of the latrines. The findings highlight the need to complement sanitation 'hardware' with the necessary health education 'software'. Ascaris eggs are useful indicators but robust standardized methods are needed for their extraction from household soils. PMID- 2918574 TI - Granulomatous peritonitis caused by Ascaris eggs: a report of three cases. AB - Three cases of granulomatous peritonitis, due to the eggs of Ascaris lumbricoides, are reported. All patients presented with a palpable mass in the abdomen and two patients, in addition, had fever and abdominal pain. Laparotomy was performed and the operative diagnosis in each case was tuberculosis. The diagnosis of Ascaris ova peritonitis was made by histopathological examination of tissue removed at operation. The pathogenesis and differential diagnosis of this condition are briefly discussed. PMID- 2918576 TI - Importance of group G streptococci in human pyogenic infections. AB - Streptococci that belong to groups other than A are involved in a variety of human infections. In the present study, we report the pyogenic infections associated with group G streptococci (GGS), observed at the Christian Medical College Hospital, Vellore, Tamil Nadu, India. Of 2314 beta-haemolytic streptococci isolated from 31,857 pus specimens processed during the period 1975 1986, GGS accounted for 338 (14.6%). Twelve of these were grown in pure culture. The clinical conditions associated with them included pyogenic arthritis, osteomyelitis, paravertebral sinus and an abdominal burst. Clinical analysis of 99 of 125 patients with GGS, grown in mixture with another organism or skin contaminants, showed that 59% of them were from surgical wound infections, diabetic lesions or wound infections in leprosy patients. Surgical management and antibiotic treatment resulted in full recovery of these clinical conditions. PMID- 2918575 TI - Mother-to-child transmission of hepatitis B virus in a semirural population in Egypt. AB - A follow-up study for one year was made on 35 babies born to HBsAg positive mothers in a semirural population in Egypt. Five of 21 babies (24%) showed HBsAg in the umbilical cord blood and remained positive throughout the observation period. At 3 months, eight of 37 babies (23%) were HBsAg + ve. At 6 months, 13 of 35 babies (37%) were HBsAg + ve and they were also still found positive at 12 months. None of 30 babies born to HBsAg-ve mothers developed antigenaemia throughout the observation period. Factors which significantly contributed to transmission were maternal educational level, family socio-economic standard, family residence, maternal e/anti-e status, and maternal schistosomal infestation. Factors which did not significantly affect transmission were maternal age, maternal parasitic non-schistosomal infestations, maternal transaminases level, order of the child in the family, and type of child feeding. Of particular note, four of five babies (80%) born to HBsAg + ve mothers who as well had schistosomiasis were HBsAg + ve throughout the observation period. PMID- 2918577 TI - Mebendazole retention enema for severe Trichuris trichiura (whipworm) infection: a case report. AB - The authors report a case of massive Trichuris trichiura infection, resulting in severe anaemia and congestive cardiac failure in a 9-year-old Iban boy, who was resistant to the usual oral anthelmintic treatment, but promptly responded to mebendazole retention enema. This patient also had an associated Entamoeba histolytica infection. PMID- 2918578 TI - Arteriomesenteric duodenal occlusion associated with strongyloidiasis. AB - Arteriomesenteric occlusion of the distal duodenum may occur in clinical conditions which result in narrowing of the angle between the aorta and superior mesenteric artery. Two patients with arteriomesenteric duodenal occlusion associated with Strongyloides stercoralis infection are described. In one patient the mechanism of occlusion appeared to be significant weight loss and associated visceroptosis, while in the other patient increased diameter of superior mesenteric vessels was the major factor. Strongyloidiasis, a curable parasitic infection, should be considered in patients presenting with arteriomesenteric occlusion of the distal duodenum. PMID- 2918579 TI - Hepatitis B virus in Saudi Arabia. AB - This study was conducted on 2702 samples collected from the male and female population in different provinces of Saudi Arabia. The overall prevalence of hepatitis B surface antigen (HBsAg) was high (16.7%) and no significant difference was encountered between the rate in males and females. Different regions of Saudi Arabia showed a significantly variable prevalence of HBsAg. The eastern province had a prevalence of about 9% compared to the southwestern province where the prevalence was 25% in Jaizan. The antibodies anti-HBs and anti HBc were encountered in 30-67% of the individuals in different provinces, suggesting that a significant number of Saudis were already immune to HBsAg before they reached adulthood. This paper presents the results obtained in different regions and shows that significant differences exist in the HBsAg carrier rate in the different regions of Saudi Arabia. The possible causes for the variation are discussed and strategies to reduce the prevalence of HBsAg carrier state are suggested. PMID- 2918580 TI - Re-evaluation of the value of ascitic fluid pH lactate dehydrogenase and total proteins in the diagnosis of spontaneous bacterial peritonitis (SBP). AB - In view of high mortality, variable clinical presentation, and late results of bacterial culture, early diagnosis of SBP and treatment are based on indirect parameters of infection. Forty-two patients with ascites and liver cirrhosis were studied. Ascitic fluid (AF) was examined for total protein content, pH, lactate dehydrogenase, amylase, absolute polymorphonuclear cell count (PMN) and for presence of bacteria by examining a fresh smear of the deposit and culture of the fluid under aerobic and anaerobic conditions. AF/serum gradient of total proteins and LDH was calculated. One patient proved to have a malignant ascites and was excluded. The remaining 41 patients fell into two groups: Group I PMN less than 250 cell mm-3, culture negative, sterile ascites, 36 patients. Group II PMN greater than 250 cell mm-3. (a) Culture positive neutrophilic ascites (SBP), three patients. (b) Culture negative neutrophilic ascites (CNNA), two patients. In both CNNA and SBP:AF/serum total LDH gradient greater than 0.75 In the sterile group: AF/serum total LDH gradient less than 0.58 There was no correlation between presence of infection and ascitic fluid pH, protein content and AF/serum total protein gradient. Therefore AF PMN greater than 250 mm and AF/serum total LDH gradient greater than 0.6 should be considered reliable, indirect parameters of infection, and CNNA a variant of SBP with a small bacterial inoculum size. PMID- 2918581 TI - Subspecialization and general urology. AB - Subspecialization within urology is growing, affecting not only teaching and research but the general practice of urology as well. To evaluate present attitudes towards subspecialization a questionnaire was sent to the membership of the Western Section of the American Urological Association. The responses from 561 members (53 per cent) were tabulated by computer and analyzed. Of those in private practice 16 per cent consider themselves to be subspecialists, although half of these have had no formal training. More subspecialize in oncology, andrology and gynecology than in pediatric urology. Opinions toward issuing certificates of special competence are mixed but opposition to board certification is general. A majority of respondents believe that subspecialization might provide better care for some patients but would increase costs, especially for tertiary care. It would not result in inferior care for patients not having access to the subspecialist. Subspecialization would be expected to reduce the economic return to the nonspecialist without increasing it for the specialist. Respondents believe that it would advance diagnosis, treatment and research in special areas, and improve training and competence but at greater expense. Finally, they express concern that subspecialization may well restrict the experience and competence of general urologists and cause conflict. PMID- 2918582 TI - Reversal of end stage renal failure with surgical revascularization in patients with atherosclerotic renal artery occlusion. AB - A total of 9 patients with end stage renal failure caused by atherosclerotic renal artery occlusion underwent surgical revascularization with subsequent recovery of renal function. The duration of dialysis preoperatively ranged from 1 week to 13 months. In all cases renal viability was being maintained by collateral vascular supply. Postoperatively, renal function improved immediately and no patient required subsequent dialysis. Excellent over-all rehabilitation was achieved in all patients. Six patients currently are alive at a mean interval of 4.0 years postoperatively and with satisfactory renal function (mean serum creatinine 2.7 mg. per dl.). Three patients died at a mean interval of 6.8 years postoperatively and they all maintained satisfactory renal function (mean serum creatinine 3.0 mg. per dl.) until death. In some patients with end stage renal failure caused by atherosclerotic arterial occlusion surgical renal revascularization can yield extended survival with freedom from chronic dialysis. PMID- 2918583 TI - Variations in fluoroscopic and spot film techniques during extracorporeal shock wave lithotripsy. AB - The radiation techniques of different operators who performed extracorporeal shock wave lithotripsy of the kidney were evaluated retrospectively. The study was limited to 9 operators who each performed more than 100 procedures on the Dornier lithotriptor. The average fluoroscopic time and number of video spot films per procedure for all operators were 4.1 minutes and 6.5, respectively. However, the average fluoroscopic time per operator varied from 1.4 to 7.6 minutes and the average number of video spot films per operator varied from 3 to 13. The results illustrate the need for some operators to reduce fluoroscopic time and video spot filming. PMID- 2918584 TI - Morbidity associated with indwelling internal ureteral stents after shock wave lithotripsy. AB - Placement of internal ureteral stents before extracorporeal shock wave lithotripsy of large stone burdens has decreased the incidence of post extracorporeal shock wave lithotripsy colic, secondary endoscopic procedures and prolonged hospital stays. However, indwelling stents have an associated patient morbidity and intolerance. A telephone survey of 50 patients (average stone burden 28 mm.) who were discharged from the hospital after treatment with an indwelling internal polymer stent was performed with a standard questionnaire. Symptoms reported with in situ internal ureteral stents included gross hematuria (42 per cent), fever or chills (20 per cent), and persistent discomfort or pain in the bladder and/or flank (26 to 38 per cent). Of the patients 44 per cent reported moderate to intolerable discomfort that was relieved by removal of the stent. The degree of symptoms was not associated with stent composition, style or length, or the presence of a transurethral string. Five patients had premature migration or dislodgment of the internal stent and 4 reported episodes of obstructive pyelonephritis requiring removal of an impacted stent or endourological intervention. Internal ureteral stents placed before extracorporeal shock wave lithotripsy have an identifiable patient morbidity while indwelling and, therefore, they should be used judiciously according to the stone burden, renal anatomy and body habitus. PMID- 2918585 TI - Clinical experience with transitional cell carcinoma of the bladder with special reference to smoking. AB - A review was done of 100 consecutive patients with carcinoma of the bladder treated by 1 physician at 1 hospital from June 1982 to December 1986. Special reference was made to the possible effect of cigarette smoking on initial stage, initial grade and recurrences. There was no significant difference in terms of initial tumor stage or grade but smokers had significantly more recurrent tumors. Also, smokers had bladder recurrences after partial cystectomy and urethral recurrences after total cystectomy. The biochemical aspects of smoking as a risk factor in bladder carcinoma are reviewed briefly. PMID- 2918586 TI - Clinical evaluation of an external urine collection device for nonambulatory incontinent women. AB - Chronic urinary incontinence is a frequent complication of a variety of neurological diseases and is a major clinical problem among the aged. Urinary incontinence may be the pivotal factor that determines whether a patient requires long-term institutional care. For management of urinary incontinence in aged, nonambulatory women use of absorbent products may not prevent decubitus ulcers, while chronic use of indwelling urethral catheters results in bacteriuria and its complications. An effective external urine collection device for women, analogous in function to the condom catheter for men, may improve care by reducing complications, averting admissions to chronic care facilities and lowering medical costs. During 125 patient-days we evaluated 63 applications of an external urine collection device on 7 incontinent women in a nursing home. Each device was allowed to remain in situ for a maximum of 48 hours. Only 14 per cent of the devices required premature replacement due to unacceptable urine leakage. The median device wear time was 48 hours. The only adverse reactions observed were minimal erythema at 2 of 63 device removals and transient periurethral edema in 1 patient, which disappeared with continued use of the device. Thus, this device, exploiting an adhesive developed for ostomy appliances, was effective in maintaining patient dryness and was not associated with severe local reactions. These results appear to warrant clinical trials for extended periods in incontinent women. PMID- 2918587 TI - Treatment of urinary incontinence by the periurethral implantation of glutaraldehyde cross-linked collagen. AB - Injectable materials have been used to augment the urethral sphincter and improve urinary continence with some success. However, none of these materials has received widespread use because they are difficult to inject and have been reported to migrate. We investigated the efficacy of transurethral implantation of glutaraldehyde cross-linked collagen, a highly purified bovine collagen. A total of 17 patients (16 men and 1 woman) with urinary incontinence resulting from a previous operation was selected for glutaraldehyde cross-linked collagen injection into the region of the urethral sphincter. Before and after implantation patients underwent urodynamic evaluation. Glutaraldehyde cross linked collagen was injected into the area of the bladder neck or urinary sphincter under direct endoscopic vision. If no improvement occurred reinjection to increase the implant volume was performed at least 3 months after a previous injection. Of the 17 patients 9 were cured or improved. No complications have been reported. This investigation shows that glutaraldehyde cross-linked collagen can be injected into the urinary tract to correct urinary incontinence without observable or measurable morbidity. PMID- 2918588 TI - Vaginal flap urethral reconstruction: an alternative to the bladder flap neourethra. AB - Vaginal flap urethral reconstruction was done in 10 women who sustained total or partial loss of the urethra, and extensive damage to the vesical neck and trigone due to operative complications. In all patients a neourethra was constructed by rolling a vaginal flap into a tube and covering the anastomosis with a labial pedicle fat pad graft and vaginal flap. Five patients underwent a concomitant pubovaginal sling procedure, 3 had a modified Pereyra operation and 1 had a modified Kelly plication. Postoperatively, 9 of the 10 patients had a satisfactory neourethra but 3 required a generous meatotomy to facilitate micturition. Two patients required temporary intermittent self-catheterization. Of the 10 patients 6 were completely continent after a single reconstruction, which included an anti-incontinence repair. Of the patients with postoperative incontinence 2 subsequently were cured with a pubovaginal sling and 1 had a vesicovaginal fistula that was successfully repaired transvaginally. These results support our contention that a vaginal flap urethral reconstruction combined with an appropriate anti-incontinence operation offers a viable and simple alternative to bladder flap urethral reconstruction. PMID- 2918589 TI - Prostaglandin E1 versus phentolamine/papaverine for the treatment of erectile impotence: a double-blind comparison. AB - The use of intracavernous prostaglandin E1 was studied in 48 organically impotent men. Eight men with previous chemical priapism did not have chemically induced priapism at up to 4 times the minimum effective dose of prostaglandin E1. Of 15 men with arteriogenic impotence who had failed prior intracavernous phentolamine and papaverine therapy 10 had adequate erections with prostaglandin E1. A total of 25 men received intracavernous prostaglandin E1 and phentolamine plus papaverine in a double-blind fashion. Erections with prostaglandin E1 were equal or superior to those with phentolamine plus papaverine in each case. PMID- 2918590 TI - Stage IE nonHodgkin's lymphoma of the testis: a need for a brief aggressive chemotherapy. AB - Primary nonHodgkin's lymphoma of the testis is a localized disease in 50 per cent of the cases. Clinical records and pathological material from 9 stage IE cancer patients treated at our institutions were reviewed. All but 1 patient had B cell type lymphomas of intermediate (6) or high (3) grade according to the Working Formulation. Mean survival was 49 months and actuarial survival was 74 per cent at 5 years. Chemotherapy differed with time and frequently was associated with subdiaphragmatic involved field and prophylactic contralateral testis radiotherapy. In view of the good prognosis of patients receiving doxorubicin based chemotherapy and recent reports on low stage nonHodgkin's lymphoma we recommend an aggressive brief therapy for stage IE lymphoma of the testis after orchiectomy. PMID- 2918591 TI - Post-chemotherapy lymph node histology in radiologically normal patients with metastatic nonseminomatous testicular cancer. AB - A total of 37 patients with initially advanced metastatic nonseminomatous testicular cancer underwent retroperitoneal lymph node dissection after cisplatin based combination chemotherapy. Abdominal computerized tomography was negative at retroperitoneal lymphadenectomy (lymph nodes not exceeding 10 mm. in the transverse computerized tomography plane). Complete necrosis and fibrosis were found in 25 patients. In 11 patients the retroperitoneal lymphadenectomy specimen showed a mature teratoma. Residual vital malignant tumor was observed in 1 patient. Neither the initial size of the retroperitoneal mass nor the histological status of the primary tumor was predictive of the histological findings in the retroperitoneal lymphadenectomy specimen. The high frequency of mature teratoma raises the question whether omitting post-chemotherapy surgery is a safe routine policy in patients with negative computerized tomography, especially if long-term followup is not feasible. We recommend a post chemotherapy retroperitoneal operation as routine treatment even in patients with negative computerized tomography. PMID- 2918592 TI - A comparison of fine needle aspiration and core biopsy in diagnosis and preoperative grading of prostate cancer. AB - Fine needle aspiration biopsy has been documented to be safe and accurate for the diagnosis of prostate cancer. A study was done based on 3 objectives to determine 1) whether performing core biopsies and fine needle aspiration in each patient with a prostate nodule increases the detection rate of prostate cancer, 2) the accuracy of preoperative grading by fine needle aspiration in predicting the final pathological grade in radical prostatectomy specimens and 3) the usefulness of fine needle aspiration in screening for unsuspected stage A prostate cancer. Of 203 consecutive patients undergoing prostate biopsies core and fine needle aspiration biopsies were performed in 121. An additional 58 patients underwent prostate biopsies just before transurethral resection of the prostate and 24 underwent radical prostatectomy. The diagnostic accuracy of fine needle aspiration was superior to that of core biopsy (82 versus 74 per cent). Performance of both biopsies yielded a higher percentage of positive diagnoses than either biopsy alone (32.2 per cent versus 24 and 28 per cent). Except in poorly differentiated cancers, fine needle aspiration is a poor predictor of final pathological grade. Fine needle aspiration is not useful in detecting stage A1 prostate cancer. Although fine needle aspiration has several distinct advantages over core biopsies, there is a definite learning curve before its use can be fully exploited. It is important to have an experienced pathologist and to perform both biopsies at each center until sufficient experience is accumulated. PMID- 2918593 TI - Total prostatectomy for clinically localized prostatic cancer: long-term results. AB - The fate of the first 52 patients with clinically localized prostate cancer who underwent total perineal prostatectomy at our clinic and have been followed for a minimum of 15 years is reviewed to evaluate the long-term impact of this operation on the disease. None of these patients received any adjuvant therapy. Nine patients (17 per cent) had recurrence and 5 (10 per cent) died of disease during this interval. The actual observed over-all survival at 15 years was 64 per cent, the actuarial survival was 67 per cent and the cause-specific survival was 90 per cent. PMID- 2918594 TI - Morbidity and mortality of local failure after definitive therapy for prostate cancer. AB - We reviewed our experience with morbidity and mortality associated with clinical local failure after definitive therapy for adenocarcinoma of the prostate by interstitial 125iodine implantation, external beam radiation therapy or radical prostatectomy. Morbid complications included unilateral ureteral obstruction; bladder obstruction and/or incontinence requiring treatment by transurethral resection, or placement of a urethral or suprapubic catheter; hematuria requiring intervention for clot evacuation or fulguration, and perineal and/or pelvic pain. Lethal complications included bilateral ureteral obstruction or bowel obstruction. We treated 108 patients with 125iodine, 178 with external beam radiotherapy and 67 with radical prostatectomy. Clinical local failure occurred in 26 per cent of the 125iodine, 17 per cent of the external beam radiotherapy and 12 per cent of the radical prostatectomy groups. The total incidence of local failure with 125iodine was statistically higher than for radical prostatectomy. Stage C and poorly differentiated tumors were associated with a statistically higher incidence of local failure compared to lower stage and grade tumors. However, within each stage and grade there was no significant difference in local failure between treatment modalities. There was negligible morbidity or mortality secondary to local failure associated with stage A2, stage B1 or well differentiated tumors regardless of treatment modality. There was no difference in the morbidity and mortality between treatment modalities for stage C or poorly differentiated tumors. However, for stage B2 or moderately differentiated tumors treated by 125iodine implantation there was a statistically greater incidence of morbidity and mortality than that associated with external beam radiotherapy and radical prostatectomy. Our observations with regard to selection of primary monotherapy options that provide local tumor control are as follows. Stage A2, stage B1 or well differentiated tumors can be well controlled by all 3 treatment modalities. 125Iodine is associated with local failure-related morbidity and mortality for stage B2 or moderately differentiated tumors, which are statistically higher than for external beam radiotherapy and radical prostatectomy, and therefore, these latter are the preferred treatment. Radical prostatectomy and 125iodine for stage C tumors are associated with a trend to higher local failure, and related morbidity and mortality than is external beam radiotherapy. However, longer followup of the external beam radiotherapy series is necessary to confirm this observation. PMID- 2918595 TI - Use of the external condom catheter to secure a temporary balloonless urethral catheter. PMID- 2918596 TI - Neuroanatomy of the pelvis in an infant with cloacal exstrophy: a detailed microdissection with histology. AB - The internal anatomy of the pelvis in the patient with cloacal exstrophy has not been described in detail previously. We present in detail the pelvic anatomical relationships of a patient with cloacal exstrophy who died 72 days after birth and whose body subsequently was perfused with a formalin-based anatomical fluid. Microdissection of the pelvis with histological confirmation of the identity of structures dissected was performed. The vascular supply to the urinary hemibladders arises from the internal iliac arteries, which pass along the lateral portion of the pelvis and enter each hemibladder. The autonomic innervation to the bladder and corporeal bodies arises from a pelvic plexus that lies on the anterior surface of the sacrum. The innervation to the hemibladders then travels in the midline along the posteroinferior surface of the pelvis before extending laterally to communicate with each hemibladder. Autonomic innervation to the duplicated corporeal bodies arises from the sacral pelvic plexus and travels in the midline to pierce the inferior portion of the pelvic floor posterior and medial to the hemibladders. These nerves then enter the crural region of the corpora. Sensory innervation to the corporeal bodies arises from the sacral trunk and passes posterior to the pelvic floor muscles, traveling just medial to the widely separated ischial spines and then laterally along the corporeal bodies. Illustrations of the anatomy and implications for management of the exstrophy patient are presented. PMID- 2918597 TI - Ectopic vas deferens, imperforate anus and hypospadias: a new triad. AB - An ectopic vas deferens is a rare congenital anomaly frequently associated with rectal abnormalities. We describe 2 patients with ectopic vas deferens associated with an imperforate anus and hypospadias. There are 19 previous reports of patients with ectopic vas deferens, 5 of which were bilateral. One of our patients, a child with bilateral ectopic vas deferens, had the highest reported insertion of an ectopic vas deferens. The embryology and management of this rare condition are reviewed. PMID- 2918598 TI - Aphallia: its classification and management. AB - Aphallia is an extremely rare disorder with profound urological and psychological consequences. Approximately 60 patients have been reported on in the literature; we report our experience with 3 additional patients. Fifty patients had sufficient information to classify the condition according to the site of the urethral meatus. With the relative relationship of the urethral meatus to the anal sphincter several observations were noted. The more proximal the meatus the higher the incidence of other anomalies and the greater the number of neonatal deaths. Of the patients 30 (60 per cent) had a post-sphincteric meatus located on a peculiar appendage at the anal verge. These patients had the lowest incidence of other anomalies (1.2 per patient) and the highest survival rate (87 per cent). A total of 14 patients (28 per cent) had pre-sphincteric urethral communications (prostato-rectal fistula), of whom 36 per cent died in the neonatal period. Six patients (12 per cent) had urethral atresia. This group had no survivors and the highest incidence of other anomalies (4 per patient). Of our patients 2 had a post-sphincteric meatus and 1 had a pre-sphincteric meatus. In addition to correction of life-threatening anomalies the management of aphallia centers on establishing gender assignment. Bilateral orchiectomy, labial construction and urethral transposition should be done in the newborn period, if possible. PMID- 2918599 TI - Massive strawberry hemangioma of the male genitalia. AB - We report a case of a massive strawberry hemangioma involving the penis and scrotum of a neonate. The lesion and its minor complications (ulceration) were managed conservatively with an excellent outcome. A conservative approach should be strongly recommended in lesions of this type. PMID- 2918600 TI - Varicocele as the presenting sign of an abdominal mass. AB - A patient with a varicocele on the right side as the presenting sign of intra abdominal Burkitt's lymphoma is reported. The incidence and etiology of varicocele are discussed. PMID- 2918601 TI - Magnetic resonance imaging in the diagnosis and followup of idiopathic retroperitoneal fibrosis. AB - Four cases of idiopathic retroperitoneal fibrosis are reported. Magnetic resonance and computerized tomographic images were obtained for diagnosis in each case, and followup scans were obtained at various intervals after therapy. In all 4 cases magnetic resonance imaging was equal or superior to computerized tomography in the diagnosis of retroperitoneal fibrosis, outlining the extent of involvement, preoperative planning and assessing response to medical or surgical therapy. PMID- 2918602 TI - Voiding dysfunction secondary to penetrating bony fragment 20 years after pelvic fracture. AB - We report a case of persistent voiding dysfunction caused by an unsuspected penetrating bony spicule 20 years after extraperitoneal bladder rupture and pelvic fracture. PMID- 2918603 TI - Removal of a strangulating metal bearing from the penis. AB - A patient presented to the emergency room with a stainless steel bearing around the shaft of the penis. There was marked edema of the entire penis distal to the constricting steel ring. A circular saw attachment used for total joint arthroplasty was used to cut this metal ring successfully. PMID- 2918604 TI - OmniPhase penile prosthesis: delayed bilateral central cable breakage. AB - The OmniPhase* penile prosthesis is a new mechanically activated penile implant. The prosthesis can be alternatively flaccid and rigid depending on the tension of a supporting central cable. We report a case of delayed bilateral central cable breakage with subsequent loss of penile rigidity. PMID- 2918605 TI - Hormone-secreting metastatic interstitial cell tumor of the testis. AB - A patient is described with a hormone-secreting interstitial cell tumor, manifesting metastasis 7 years after removal of a reportedly benign primary tumor. The late course of the disease was followed by computerized tomography and serum hormone assays. Previously reported cases of metastatic interstitial cell tumor are reviewed, and prognostic features and treatment are discussed. PMID- 2918606 TI - Isolation and characterization of collagen in Peyronie's disease. AB - Peyronie's disease is characterized histologically by excessive collagen deposition in the lesion. We examined the collagen types in Peyronie's disease plaque tissues compared to unaffected tissues from the same patient, other control tissues, and Dupuytren's contracture. Gel electrophoresis of pepsin solubilized collagen demonstrated the presence of type I collagen and an increased content of type III collagen in plaque tissue. Increased type III collagen was detected in apparently normal tissue adjacent to the plaque and in Dupuytren's lesion, confirming previous findings. Although the cause of excessive collagen accumulation of Peyronie's disease is unknown, the results suggest an imbalance in the regulation of extracellular matrix production leading to pathologic fibrosis. PMID- 2918609 TI - A study of the incorporation of urinary macromolecules onto crystals of different mineral compositions. AB - A new method used to study the binding of proteins onto calcium oxalate crystals demonstrated this interaction to be a selective process regarding the types of adsorbed proteins. To determine whether the incorporation of urinary macromolecules onto crystals formed in urine in vitro is dependent on the specific crystalline composition, this technique was applied to both uric acid and calcium oxalate crystals. Powdered uric acid was dissolved in urine and the pH lowered to 5.5. The resulting uric acid crystals were centrifuged and the pellet dialyzed against water at pH 8.0. Calcium oxalate crystals produced by the addition of 0.1 M calcium chloride and 0.1 M sodium oxalate to an aliquot of the same urine sample were demineralized with 5% EDTA. Gel filtration chromatography was used to isolate the protein fraction of an aliquot of the urine samples before and after crystallization of uric acid and calcium oxalate. The proteins recovered from the crystals and urine samples were separated by two-dimensional polyacrylamide gel electrophoresis. Analysis of the gels confirmed that the binding of urinary proteins onto crystals is a selective process and indicate that this interaction is dependent on the specific inorganic composition of the crystals. PMID- 2918607 TI - Measurement of urinary antibodies to crude bacterial antigen in patients with chronic bacterial prostatitis. AB - Measurements of IgG and IgA antibodies against common gram negative organisms in pre and post prostatic massage urines were investigated. Lower tract urinary localization specimens were obtained in men with chronic bacterial prostatitis, nonbacterial prostatitis, and without evidence of infection. Quantitative cultures were performed on all specimens. A rapid and simple enzyme-linked immunosorbant assay (ELISA) was developed to measure urinary total immunoglobulins and antibodies to common gram negative organisms (mixed antigen specific antibodies, MASA). Comparison with a previously developed radioimmunoassay yielded a correlation determinant of 0.89 per cent. Almost all patients had post prostatic massage urinary IgA and IgG levels that were higher than the premassage levels, reflecting the presence of prostatic fluid in the postmassage specimens. In only the patients with chronic bacterial prostatitis, however, were levels of IgA or IgG MASA in the postmassage urines higher than those measured in the premassage urines. This same elevation was found in the urinary specimens from men who could not be diagnosed to have bacterial prostatitis by traditional means on a specific occasion because of antibiotic treatment, inadequate specimens, or bacteriuria, but had chronic bacterial prostatitis confirmed traditionally on another occasion. No detectable MASA were measured in either the pre or postmassage urines of men without a history of previous urinary infections. From these data it appears that urinary MASA may be used to diagnose bacterial prostatitis in situations in which quantitative bacteriologic cultures cannot be performed. These measurements may, furthermore, be used to diagnose chronic bacterial prostatic infection in men who cannot be diagnosed to have bacterial prostatitis when prostatic fluid is unobtainable or culture results are uninterpretable. PMID- 2918608 TI - The action of pinacidil in the isolated human bladder. AB - The need for effective symptomatic treatment of patients with detrusor hyperactivity is widely recognized. In search of new principles of decreasing bladder contraction we have studied the effects of pinacidil on the isolated human bladder. Pinacidil is a recently developed antihypertensive agent classified as a K+ channel opener, and is believed to depress smooth muscle activity by this action. Pinacidil concentration-dependently depressed contractions elicited by carbachol, low concentrations of K+ (less than 60 mM) and electrical stimulation. In addition it caused a concentration-related increase in the efflux of 86Rb from preloaded detrusor cells. The effects on 86Rb efflux could be inhibited by tetraethylammonium chloride and procaine, but not by apamin, agents known to block K+-channels. The results support the view that part of the pinacidil effect on the human bladder is caused by an opening of K+ channels, efflux of K+ and subsequent hyperpolarization of the detrusor cells. Clinical testing of this new therapeutic principle for treatment of bladder hyperactivity seems justified. PMID- 2918610 TI - Quantitative analysis of outflow pathway of corpora cavernosa by pressure flow technique. AB - Using a pressure flow technique, quantitative analysis of the physiological characteristics of the outflow pathway of the corpus cavernosum was carried out in 19 male dogs weighing 7.5 to 23.0 kg. Pressure flow curves were made on dogs whose pelvic nerve was stimulated electrically and on dogs left unstimulated. When a cyclical change in saline perfusion rate was applied without nerve stimulation, the variable of the intracorporeal pressure showed a large hysteretic loop, indicating that the resistance of the outflow canals to flow was altered by the distension of the sinusoidal space. In dogs whose pelvic nerve was stimulated, the pressure flow curves shifted to the left side in comparison with the outward phase of the pressure flow curve of animals without pelvic nerve stimulation, and this curve piled on the returning phase. No hysteretic relation was observed between the outward and returning phase of the pressure flow curve with pelvic nerve stimulation, but in the detailed analysis, in which the % flow rate was used instead of actual flow rate of saline perfusion, a small hysteretic loop based on the difference of the elasticity of the outlet canals was found. The distension of the corpora cavernosa and the pelvic nerve electrostimulation probably act as the triggers of the same occlusive mechanism in the outflow pathway. The percentage decrease in the blood flow in the outflow canal of the corpus cavernosum induced by the distension of the sinusoidal space or by the pelvic nerve electrostimulation was 69.6 +/- 14.4% (mean +/- SD). PMID- 2918611 TI - The rat as a model for the study of penile erection. AB - A model has been developed for the study of penile erection in the Sprague-Dawley rat. Anatomical dissections demonstrate a bilateral ganglion lateral to the prostate called the major pelvic ganglion. This ganglion receives input from the pelvic and hypogastric nerves and innervates the pelvic viscera. A large fiber from the major pelvic ganglion courses along the urethra and innervates the corpus cavernosum, the cavernous nerve. In 40 animals, electrical stimulation of either the cavernous nerve or the pelvic nerve resulted in reproducible repetitive tumescence of the corpora cavernosum. Following ablation of the cavernous nerve, electrical stimulation failed to produce erections. Standard mating behavior tests of mounting, intromission and ejaculation in 38 rats showed that surgical ablation of the cavernous nerve resulted in a decrease in the rate of intromissions and ejaculations compared with sham operated controls. Present models for the study of erection have been limited to the dog, monkey and cat. The rat model presented here offers several advantages over these existing models: 1) the cavernous nerve is easily identified, 2) electrical stimulation is easily accomplished and reproducible, 3) behavioral and neurophysiological studies are possible, and 4) animal purchase, housing, and maintenance costs are low. These advantages make this model a uniquely useful tool in the further study of penile erection. PMID- 2918612 TI - A comparison of urologic application of bipolar versus monopolar five French electrosurgical probes. AB - Urologic endoscopic procedures often involve electrosurgery. Recently bipolar probes have become commercially available. This study compares monopolar and bipolar electrosurgical probes in relation to power losses in urologic endoscopic instruments with the infusion of sterile water and saline, and the power transmitted by probes to tissue correlated to tissue destruction in each fluid. The power losses through each instrument in both solutions were minimal. The bipolar electrode functioned at a much lower power output than did the monopolar electrode. The bipolar probe was also more effective in saline than sterile water. The depth, width and volume of tissue damage for both electrodes were found to vary with generator power output. The data shows the burns had similar diameters for both probes but the bipolar probe caused significantly less burn depth than the monopolar probe. These initial studies indicate that bipolar electrodes can function in normal saline with less depth damage compared to the monopolar probe. PMID- 2918613 TI - Effects of shock waves on the rat ovary. AB - The studies reported in this paper were undertaken to investigate the effect of shock waves on ovarian function. In an initial study, five female Wistar rats underwent general anesthesia. One ovary was then exposed to 1500 shock waves at 20 kV using the Dornier XL-1 experimental lithotripter. One week following this treatment, the animals were sacrificed and both ovaries were step sectioned. We counted all follicles that contained both an oocyte and antrum. These follicles in turn were classified further as being healthy or atretic. No statistical difference in these counts was observed between shocked and unshocked ovaries taken from the same animal. In the definitive study, thirty-one adult female Wistar rats underwent unilateral oophorectomy. These rats were then divided into treated, sham-treated and control groups. The eleven treated animals were given general anesthesia and received 1500 shocks at 15 kV directed at their remaining ovary using the Dornier XL-1 lithotripter. The ten sham treated animals received identical anesthesia and duration of waterbath immersion as the treated group. In contrast, however, sham treated animals were positioned outside the path of the focused shock wave. The control group received no treatment. Normal estrus cycle was maintained in all groups following shock wave exposure. Two weeks after this exposure, all three groups of animals were allowed to mate. All animals in each of the three groups became pregnant. There was no statistical difference in litter size or fetal weights at three weeks gestation. No gross teratogenic effects were observed. The rat ovary appears to be structurally and functionally resistant to the shock wave energy levels used in this experiment. PMID- 2918614 TI - Effects of shock waves on the structure and growth of the immature rat epiphysis. AB - The left proximal tibia of eighteen five week old male Sprague-Dawley rats was exposed to 1500 shock waves at 20 kV in a Dornier XL-1 experimental lithotripter. Six of these rats, and six age-matched controls, were sacrificed two, four and ten weeks later. Eight of 18 (44%) of treated animals had lesions of focal growth plate dysplasia attributable to treatment. In the absence of extensive lesions, no significant difference was identified in the growth plate thickness of shocked versus unshocked limbs. In the group sacrificed at ten weeks, two of six (33%) treated animals had extensive dysplastic lesions which were associated with marked shortening of the shocked limb. In the absence of extensive lesions, there was no significant shortening of shocked limbs. Shock wave exposure of the rat epiphysis can affect subsequent bone growth. PMID- 2918615 TI - Primary hyperparathyroidism. AB - Hyperparathyroidism was described initially in the mid 1920s in patients suffering from a rare and severe form of bone disease, osteitis fibrosa cystica. In the 1940s and 1950s renal stone disease was recognized as a far more frequent complication of primary hyperparathyroidism than bone disease, and approximately half of the patients with primary hyperparathyroidism in clinical series published through the 1970s presented with renal stones. The introduction of routine determination of serum calcium concentration in the mid 1970s has had a dramatic impact on the frequency with which primary hyperparathyroidism is diagnosed in the population, particularly in older individuals with predominantly nonspecific symptoms of the disease. Stone complications appear to occur in less than 10 per cent of such patients. Underlying primary hyperparathyroidism is diagnosed in approximately 1 to 5 per cent of the patients with calcium stone disease. The predominant risk factor for stone formation in primary hyperparathyroidism is hypercalciuria, and patients typically present with moderate to marked hypercalciuria but with only mild hypercalcemia, in the range of 11 mg. per dl. or less. Hypercalciuria in these patients is principally the result of 1,25-dihydroxyvitamin D-mediated hyperabsorption of calcium from the intestine. The pattern of hypercalciuria disproportionate to the degree of hypercalcemia that typifies patients with primary hyperparathyroidism and stone disease reaches an extreme degree in patients with so-called subtle or normocalcemic primary hyperparathyroidism, in whom diagnosis by routine techniques may be difficult. Parathyroid exploration remains the treatment of choice in patients with primary hyperparathyroidism and stone complications. PMID- 2918616 TI - Clinical and laboratory approaches for evaluation of nephrolithiasis. AB - The initial part of this presentation deals with the sensitivity of tests commonly used in the diagnosis of primary hyperparathyroidism. Total serum calcium levels often are normal in patients with small parathyroid adenomas but levels of serum ultrafilterable and/or ionized calcium usually are elevated in these patients. The recent introduction of improved radioimmunoassays for measurement of circulating parathyroid hormone has led to greatly improved sensitivity of this test for the diagnosis of primary hyperparathyroidism. However, measurement of total urinary cyclic adenosine monophosphate, even when expressed as a function of glomerular filtration rate, is an extremely insensitive test in patients who have parathyroid adenomas weighing less than 1 gm. Consequently, this test no longer is used for diagnostic purposes in our laboratory. Data relating to the prevalence and causes of hyperoxaluria in patients with idiopathic calcium oxalate stones also are presented. Hyperoxaluria (more than 450 mumol. per 24 hours) was found in 21 of 99 consecutive untreated male patients. Approximately a third of the patients with high normal or increased urinary oxalate excretion also have increased urinary glycolate excretion, which is indicative of increased endogenous oxalate production. This metabolic abnormality was unresponsive to pyridoxine administration but preliminary findings suggest that it may be corrected by restricting dietary protein. PMID- 2918617 TI - Clinical and laboratory approaches for evaluation of nephrolithiasis. AB - A medical history and laboratory investigation of patients with recurrent stones serve as the cornerstone for preventive and therapeutic treatment. Identifiable risk factors can be discovered in 90 per cent of the patients. More sophisticated analyses of urinary supersaturation can be helpful in resistant cases. PMID- 2918618 TI - Overview of surgical treatment of urolithiasis with special reference to lithotripsy. AB - In the early 1980s, 2 elegant innovations were added to open surgery in the management of stones: endourology and extracorporeal shock wave lithotripsy. The decision strategy for treating stones is not yet codified and it depends on several factors, such as equipment, type and size of stones, needs of the patient and skills of the surgeon. After open stone surgery convalescence lasts approximately 4 to 6 weeks and repeated surgery is more difficult. With endourology convalescence can be reduced to a few days in an uncomplicated case, the risk of complication is approximately 10 per cent and retreatment is not more complicated. Convalescence with extracorporeal shock wave lithotripsy often is negligible and some extracorporeal shock wave lithotripsy units are run on an outpatient basis. However, as with all stone surgeries, extracorporeal shock wave lithotripsy causes renal bleeding of varying degrees. There are reports of diastolic hypertension after extracorporeal shock wave lithotripsy in up to 8 per cent of the patients. Retreatment is easy but the late consequences of retreatment are unknown. Extracorporeal shock wave lithotripsy is the dominant means of surgical management for stones in the western world; 87 per cent of our patients are treated with extracorporeal shock wave lithotripsy and 4 per cent with open surgery. PMID- 2918619 TI - The role of percutaneous surgery in renal and ureteral stone removal. AB - Percutaneous procedures are appropriate for a wide variety of renal and ureteral stones. In the era of shock wave lithotripsy percutaneous procedures usually are indicated in stones for which extracorporeal shock wave lithotripsy is not appropriate. Many of these situations occur in patients with large stones, and stones associated with obstruction and other problems. Indications for percutaneous stone removal and indications for open surgery are discussed. PMID- 2918620 TI - Prevention and treatment of kidney stones. Role of medical prevention. AB - Despite dramatic advances in stone removal brought by extracorporeal shock wave lithotripsy, there is a continuing need for medical diagnosis and prevention. Justifications for the medical approach include prevention of recurrence (medical treatment could prevent further stone formation, unlike a surgical approach), efficacy of prophylactic program (recurrent stone formation may be inhibited in most patients using a variety of treatment programs), inhibition of spontaneous passage (by medical treatment, although not amenable to surgical treatment), potential avoidance of renal colic (occurring before stone removal avoided by preventing recurrence), reduced need for stone removal (achieved by successful medical treatment), correction of extrarenal manifestations (deleterious extrarenal manifestations of a stone-forming condition, such as bone disease in distal renal tubular acidosis, may be corrected by appropriate medical treatment) and cost-effectiveness. The cost of medical care is estimated to be half to a fourth that of surgical care. The need and type of medical treatment should be appraised continually to accommodate advances in techniques of stone removal. PMID- 2918621 TI - The doctors' dilemmas. PMID- 2918622 TI - Renal endarterectomy through the transected aorta: a new technique for combined aortorenal atherosclerosis--a preliminary report. AB - The optimal surgical management of combined aortic and renal atherosclerosis has not been defined. A modified technique of renal endarterectomy performed through the transected aorta before anastomosis of the aortic prosthesis is presented. The surgical course and early follow-up results of the first 44 consecutive patients treated by this technique are reported. Twenty-three patients (25%) had symptomatic coronary artery disease, 36 patients (82%) had arterial hypertension, and 28 patients (64%) had elevated serum creatinine levels (mean 2.10 mg/dl). Primary indications for operation related to aortic disease in 39 patients (89%) and to poorly controlled hypertension in five patients (11%). Seventy-five renal arteries were revascularized; 11% of these arteries were occluded. Revascularizations were bilateral in 27 patients (61%), involved a solitary kidney in three patients (6%), and were unilateral in 14 patients (32%). Aortobifemoral bypass grafting was performed in 16 patients (36%), aortoiliac bypass was performed in 15 patients (34%), and infrarenal aortic replacement was performed in 11 patients (25%). Postoperative complications developed in 14 patients (32%). There were two postoperative deaths (4%). Nineteen patients had transient increases in serum creatinine levels greater than 0.5 mg/dl. Two patients required postoperative dialysis, neither related to failure of their renal revascularization. There were five late deaths, all as a result of myocardial infarction. Renal function improved in four patients and remained stable in 22 patients. Blood pressure was improved in 64% of patients previously hypertensive. These preliminary results indicate that renal endarterectomy through the transected aorta along with aortic reconstruction is a safe, efficient, and effective means of treating these complex lesions. PMID- 2918623 TI - Massive pulmonary embolism: triple-armed therapy. AB - Many patients who suffer a massive pulmonary embolus die despite emergent therapy. In these desperately ill patients an aggressive, combined method of management was initiated to improve their chances and quality of survival. During a 5-year period 10 patients were treated with (1) low-dose topical, intrapulmonary thrombolytic therapy to dissolve thrombus, (streptokinase or urokinase); (2) anticoagulation to prevent thrombus propagation (heparin); and (3) the simultaneous insertion of a Greenfield filter to prevent the early, recurrent, and therefore potentially fatal pulmonary embolus--"triple-armed therapy." Thrombolytic therapy was administered through a Swan-Ganz catheter wedged against the pulmonary embolus. During the same interval 10 other patients also sustained massive pulmonary emboli but were treated only with systemic heparin. Serial pulmonary arteriography was performed daily. The patients treated by triple-armed therapy responded favorably with a rapid (less than 6 hours), significant improvement in PaO2, pulmonary artery pressure, cardiac output, pulmonary vascular resistance, and blood pressure, compared with patients treated with continuous heparin alone. Nine patients in the triple-armed therapy group survived whereas only six in the heparin group survived. Two additional patients were treated by triple-armed therapy and had thrombolysis with triple-armed therapy with tissue plasminogen activator; these patients demonstrated the most rapid improvement in cardiorespiratory dynamics and arteriographic clearance of emboli. This management protocol shows promise for patients who sustain a massive pulmonary embolus, because it reduces the morbidity associated with pulmonary embolectomy while avoiding the hazards associated with systemic thrombolytic therapy. PMID- 2918624 TI - Species variation and the success of endothelial cell seeding. AB - In vivo seeding of vascular grafts in dogs has resulted in the formation of a confluent luminal monolayer and increased patency. Results of similar trials in humans have been mixed. Interspecies variation of the harvest, attachment, and growth of vascular endothelium might explain these apparent differences. Endothelial cells were harvested by standard enzymatic techniques from bovine aorta (n = 7), canine external jugular vein (n = 9), and human saphenous vein (n = 8). Growth curves were generated by means of a replicate microwell technique and then compared with the following observations: Harvest of endothelium from human saphenous vein provides a lower yield of viable endothelial cells. When compared to bovine or canine cells, the lag phase of the growth curve of human cells is prolonged and the doubling time in the growth phase is increased. These results suggest that in humans there are fewer available cells, and conditions for endothelial cell growth may be more stringent than for other species. It may be necessary to develop alternative methods of seeding before success in humans can be achieved. PMID- 2918625 TI - Spinal cord ischemia: an evaluation of pharmacologic agents in minimizing paraplegia after aortic occlusion. AB - Superoxide dismutase (SOD), barbiturates, and hypothermic crystalloid were evaluated for their effectiveness in minimizing ischemic damage to the spinal cord at 40 minutes of aortic occlusion. Forty-two dogs underwent proximal and distal thoracic aortic occlusion for 40 minutes with infusion of test agents into the occluded segment. The dogs were divided into six groups. Group 1 (n = 6) served as control. Group 2 (n = 6) received hypothermic crystalloid. Group 3 (n = 6) animals received thiopental. Group 4 (n = 7) received SOD. Group 5 (n = 9) received hypothermic crystalloid and thiopental. Group 6 (n = 8) received hypothermic crystalloid, thiopental and SOD. The animals were observed for neurologic deficit for 72 hours. In group 1, six of six dogs showed complete paralysis. Five of six dogs from group 2, five of six dogs from group 3, and five of seven dogs from group 4 showed complete paraplegia. The remaining dogs in these groups showed varying degrees of recovery. Four of nine dogs in group 5 had complete paraplegia, three dogs showed varying degrees of recovery, and two dogs had no neurologic deficit. In group 6, one dog had complete paraplegia, three had partial recovery, and four had no neurologic deficit. Group 6 was the only group that showed significantly less late neurologic impairment than the control group. We concluded that although cold perfusion, barbiturates, and SOD are not protective when used alone, they are effective when all are used in combination. The combination of cold perfusion, barbiturates, and SOD significantly decreases neurologic deficit after 40 minutes of aortic occlusion. PMID- 2918626 TI - Flow patterns in the abdominal aorta under simulated postprandial and exercise conditions: an experimental study. AB - Specific hemodynamic factors have been shown to be associated with atherosclerotic plaque localization at the human carotid bifurcation. Flow field characteristics may also determine plaque distribution in the abdominal aorta. We therefore characterized flow patterns in a glass model abdominal aorta that included its major branches under conditions of steady flow. Outflow resistances of the celiac, superior mesenteric, renal, inferior mesenteric, and iliac arteries were varied to produce flow distributions consistent with rest, the postprandial state, and vigorous lower limb exercise. Flow patterns were visualized with three colors of dye injected simultaneously through capillary tubes at selected locations and recorded as still photographs and by cinephotography on videotapes. Under resting conditions a large region of flow separation and stagnation occurred at the posterior wall of the aorta directly opposite the orifices of the superior and inferior mesenteric arteries. Similar separation regions were observed during the simulated postprandial state but diminished markedly when distal outflow was increased to levels consistent with exercise. In the highly susceptible infrarenal aortic segment, beginning about 2 cm below the renal artery orifices, multiple secondary flow patterns with three to four counterrotating vortex formations were observed under both resting and postprandial conditions but disappeared in the exercise state. Secondary flow patterns were not noted in the suprarenal abdominal aorta, which is usually relatively spared. Such features have been related to plaque localization elsewhere, and the disappearance of these patterns with increased flow velocity during exercise is consistent with the previously noted protective effect of unidirectional laminar high-flow states. The beneficial effects of physical fitness programs may be related in part to these hemodynamic modifications. PMID- 2918627 TI - Upper extremity arterial injury in athletes. AB - Between 1983 and 1986, 23 athletes were evaluated for arm and hand complaints. Eleven players had symptoms of thoracic outlet compression. Severe arm fatigue (eight patients) and finger ischemia (three patients) were the presenting symptoms. In the remaining 12 athletes, symptoms of hand ischemia were predominant. Noninvasive testing with Doppler ultrasonography and duplex scanning (positional testing and finger systolic pressure recording) and cold immersion were used to aid in diagnosis. In the 11 athletes with thoracic outlet compression, arteriography confirmed the finding with compression of the subclavian artery in five, the axillary artery in one, both subclavian and axillary arteries in two, posterior humeral circumflex artery in one, and subclavian aneurysm in two. Compression of the suprascapular artery was identified in four, the subscapular artery in two, and the posterior humeral circumflex artery in one. Thrombosis of a first baseman's ulnar artery and occlusion of the palmar arch in a frisbee player were documented by arteriography. Decompression of the thoracic outlet consisted of anterior scalenectomy in five, pectoralis minor muscle division in one, and resection of both muscles in two. Removal of cervical rib with interposed vein graft was performed in the two players with arterial aneurysm. Hand ischemia in the remaining athletes was treated conservatively with Dextran-heparin infusion for acute ischemia. Repeat noninvasive study of all players demonstrated absence of compression in their playing position, and all have resumed their playing careers. Hand ischemia in athletes can be evaluated noninvasively and treated conservatively. Resection of hypertrophied muscles to decompress the thoracic outlet together with release of branch artery compression in selected athletes promotes perfusion to arm and shoulder muscles and helps to avoid the catastrophic complication of repetitive trauma leading to sudden arterial thrombosis. PMID- 2918628 TI - Mesenteric venous thrombosis. AB - Sixteen patients with mesenteric venous thrombosis were reviewed retrospectively during a period from 1983 to 1987. Twelve patients had progressive abdominal pain, three had gastrointestinal bleeding, and one had general malaise. Seven of these 16 patients had previous deep-vein thrombosis. After negative routine gastrointestinal and hepatobiliary evaluation, 11 patients underwent an infusion computerized tomographic scan. Of these, 10 had superior mesenteric vein thrombosis; three of these 10 patients had portal vein thrombosis. Selective arteriography was done in two patients because of gastrointestinal bleeding, and a diagnosis of mesenteric vein thrombosis was made on the venous phase of the examination. The remaining four patients developed acute abdominal symptoms requiring surgical exploration, at which time mesenteric venous thrombosis was discovered. An identifiable coagulopathy was detected in nine patients (protein C deficiency in six, protein S deficiency in two, and factor IX deficiency treated with factor IX concentrate in one). No case of congenital antithrombin-III deficiency was identified. Six of these nine patients had a past history of deep venous thrombosis. Of five patients who underwent surgical exploration, all required bowel resection. In follow-up, two patients died of intestinal necrosis and a third died of associated pancreatic cancer. Thirteen patients were discharged from the hospital. Treatment of coagulopathy was by heparin in three patients and sodium warfarin (Coumadin) in four patients. Long-term anticoagulation was not instituted because of gastrointestinal bleeding in three and cirrhosis in three patients. Mesenteric venous thrombosis can occur without gangrenous bowel. Diagnosis should be suspected when acute abdominal symptoms develop in patients with prior thrombotic episodes and a coagulopathy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918629 TI - Research initiatives in vascular surgery. Seminar sponsored by the Society for Vascular Surgery and the International Society for Cardiovascular Surgery, with the cooperation of the National Institutes of Health and the National Heart, Lung, and Blood Institute. Bethesda, Md., Feb. 19-20, 1988. Abstracts. PMID- 2918630 TI - Can change in life-style reduce failure of arterial reconstructions? PMID- 2918631 TI - Synchrotron transvenous angiography holds promise in coronary studies. PMID- 2918632 TI - Forensics experts tackle task of identifying thousands of 'disappeared' victims. PMID- 2918633 TI - Where are the children of the 'dirty war'? Science seeks answers for their relatives. PMID- 2918634 TI - New visceral transplants invigorate cancer victims. PMID- 2918635 TI - Low-osmolar contrast agents. PMID- 2918636 TI - Repeated blood donations and erythropoietin levels. PMID- 2918637 TI - Clindamycin for staphylococcal skin infections in AIDS. PMID- 2918638 TI - Trauma systems. PMID- 2918639 TI - Crime labs or the street for drug information? PMID- 2918641 TI - Boxing-related injuries in the US Army, 1980 through 1985. AB - Boxing-related injuries, serious enough to involve hospitalization in US Army hospitals, were studied from 1980 through 1985. On average, there were 67 hospitalizations annually, with the injured spending an average of 5.1 days in bed and 8.9 days disabled, unfit for duty. There was one death from serious head injury and one instance of unilateral blindness from ocular trauma requiring enucleation. Head injuries accounted for 68% of all the injuries and were more common in the younger and presumably less experienced boxers. The advisability of continued promotion of boxing in the military needs to be addressed. PMID- 2918642 TI - The torturer's horse. PMID- 2918640 TI - Transplantation of multiple abdominal viscera. AB - Two children with the short-gut syndrome and secondary liver failure were treated with evisceration and transplantation en bloc of the stomach, small intestine, colon, pancreas, and liver. The first patient died perioperatively, but the second lived for more than 6 months before dying of an Epstein-Barr virus associated lymphoproliferative disorder that caused biliary obstruction and lethal sepsis. There was never evidence of graft rejection or of graft-vs-host disease in the long-surviving child. The constituent organs of the homograft functioned and maintained their morphological integrity throughout the 193 days of survival. PMID- 2918643 TI - The desperate case: CARE (costs, applicability, research, ethics) PMID- 2918644 TI - Diagnostic and therapeutic technology assessment. Gastric restrictive surgery. PMID- 2918645 TI - A piece of my mind. First day. PMID- 2918646 TI - Large trial finds ticlopidine superior to aspirin in preventing stroke. PMID- 2918647 TI - This St Patrick's Day finds no lack of controversy at Irish Medical Journal. PMID- 2918648 TI - In-hospital cardiopulmonary resuscitation. PMID- 2918649 TI - Denial of the AMA-endorsed disability insurance program owing to marriage counseling. PMID- 2918650 TI - Attack ferrets? PMID- 2918651 TI - The New York State Medical Society Impaired Physician Program. PMID- 2918652 TI - Cigarette smoking and exposure to passive smoke are risk factors for cervical cancer. AB - Personal cigarette smoking and exposure to passive smoke as risk factors for cervical cancer were examined in a population-based, case-control study conducted in Utah. Personal cigarette smoking was found to increase the risk of cervical cancer, after adjusting for age, educational level, church attendance, and sexual activity. The adjusted risk estimate associated with being a current smoker was 3.42 (95% confidence interval [Cl], 2.10 to 5.57); for having smoked for 5 or more pack-years, it was 2.81 (95% Cl, 1.73 to 4.55); and for having smoked at least 100 lifetime cigarettes, it was 2.21 (95% Cl, 1.44 to 3.39). The adjusted risk estimate (also adjusted for actual cigarettes smoked) associated with passive smoke exposure for 3 or more hours per day was 2.96 (95% Cl, 1.25 to 7.03). Risk from passive smoking was greater in women who were not smokers (odds ratio, 3.43; 95% Cl, 1.23 to 9.54) than in women who smoked (odds ratio, 2.59; 95% Cl, 0.23 to 29.24). PMID- 2918653 TI - Standard of care and anesthesia liability. AB - For the past 3 years, the Committee on Professional Liability of the American Society of Anesthesiologists has been studying records of closed malpractice claims files for anesthesia-related patient injuries. The database of 1004 lawsuits was examined to define the impact of the "standard of care," as judged by a practicing group of anesthesiologists, on the likelihood and amount of financial recovery. We found that payment was made in more than 80% of claims made by patients who were judged to have received substandard anesthetic care. Payment also was made in more than 40% of claims when the anesthesia care was judged to be appropriate. We conclude that in the tort-based system of compensation for anesthesia-related injury, the patient has a high probability of financial recovery for injury caused by substandard care. However, if the anesthesiologist provides appropriate care there is still a greater than 40% chance that payment will be made for the claim of malpractice. PMID- 2918654 TI - The taxes of sin. Do smokers and drinkers pay their way? AB - We estimate the lifetime, discounted costs that smokers and drinkers impose on others through collectively financed health insurance, pensions, disability insurance, group life insurance, fires, motor-vehicle accidents, and the criminal justice system. Although nonsmokers subsidize smokers' medical care and group life insurance, smokers subsidize nonsmokers' pensions and nursing home payments. On balance, smokers probably pay their way at the current level of excise taxes on cigarettes; but one may, nonetheless, wish to raise those taxes to reduce the number of adolescent smokers. In contrast, drinkers do not pay their way: current excise taxes on alcohol cover only about half the costs imposed on others. PMID- 2918656 TI - Monitoring anesthetic care: new directions. PMID- 2918655 TI - Hyperprolactinemia and nonpuerperal mastitis (duct ectasia). AB - In 108 patients with nonpuerperal mastitis (inflammatory symptoms of duct ectasia), serum prolactin levels were determined before, during, and after treatment. Twenty-nine patients (26.8%) exhibited transiently elevated prolactin levels during the period of inflammation (mean +/- SD level, 42 +/- 22 micrograms/L) that returned to normal within 4 weeks. Twenty-two patients (20.4%) presented with more severe hyperprolactinemia (78 +/- 56 micrograms/L), and 15 were found to have pituitary microadenomas. In 11 cases, mastitis was the first symptom of hyperprolactinemia. A second group of 83 patients with known hyperprolactinemia and 83 normoprolactinemic controls were interviewed with regard to recent symptoms or past treatment of nonpuerperal mastitis. Sixteen hyperprolactinemic women (19.3%) and none of the controls reported that they had experienced mastitis. We conclude that duct ectasia is due in part to increased prolactin secretion. Thus, nonpuerperal mastitis may be a symptom of hyperprolactinemia. On the other hand, nonpuerperal mastitis may induce transient hyperprolactinemia (neurogenic hyperprolactinemia) of about 3 weeks' duration that is less pronounced than central hyperprolactinemia. PMID- 2918657 TI - A piece of my mind. Yomin's star. PMID- 2918658 TI - Maternal, child health needs noted by two major national study groups. PMID- 2918659 TI - Scope, specifics of maternal drug use, effects on fetus are beginning to emerge from studies. PMID- 2918660 TI - Interaction of drug-abusing mother, fetus, types of drugs examined in numerous studies. PMID- 2918661 TI - Combinations of drugs taken by pregnant women add to problems in determining fetal damage. PMID- 2918662 TI - Leads from the MMWR. Mumps--United States, 1985-1988. PMID- 2918664 TI - Maternal brain death during pregnancy. PMID- 2918663 TI - Prenatal screening for hepatitis B antigen. PMID- 2918665 TI - Compelled medical treatment of pregnant women. PMID- 2918666 TI - Priapism in Kawasaki disease. PMID- 2918667 TI - Long-lasting behavioral changes following prednisone withdrawal. PMID- 2918668 TI - Extracorporeal shock wave lithotripsy: what does the surgeon do? PMID- 2918669 TI - The soda crush. PMID- 2918670 TI - One child, one family. PMID- 2918671 TI - Temporal patterns of cocaine use in pregnancy. Perinatal outcome. AB - Seventy-five cocaine-using women enrolled in a comprehensive perinatal care program were divided into two groups: those who used cocaine in only the first trimester of pregnancy (group 1 [N = 23]) and those who used cocaine throughout pregnancy (group 2 [N = 52]). Perinatal outcomes of these pregnancies were compared with perinatal outcomes of a matched group of obstetric patients with no history or evidence of substance abuse (group 3 [N = 40]). Group 2 women had an increased rate of preterm delivery and low-birth-weight infants as well as an increased rate of intrauterine growth retardation. Group 1 women had rates of these complications similar to the drug-free group. Mean birth weight, length, and head circumference for term infants were reduced in only the group 2 infants. However, both groups of cocaine-exposed infants demonstrated significant impairment of orientation, motor, and state regulation behaviors on the Neonatal Behavioral Assessment Scale. PMID- 2918672 TI - HIV seroprevalence in newborns in New York State. AB - The prevalence of human immunodeficiency virus (HIV) infection was determined in women at the time of childbirth throughout New York State between November 30, 1987, and November 30, 1988. Mandatory blood specimens (276,609) obtained from all newborns were examined for HIV. The overall HIV seroprevalence rate was 0.66% (1816 newborns), with 0.16% in Upstate New York and 1.25% in New York City. Rates for newborns whose mothers were aged 20 to 29 years (1.30%) and 30 to 39 years (1.35%) were significantly higher than rates for those with mothers younger than 20 years of age (0.72%). Rates of seropositivity were higher among blacks (1.8%) and Hispanics (1.3%) than among whites (0.13%). Seropositivity of HIV was higher in zip code areas with high rates of drug use (2.2%) than in the rest of New York City (0.8%). It is estimated that more than 726 HIV-infected children were born in New York State during the 1-year study period, using 40% as the probable proportion of seropositives that will become infected. PMID- 2918673 TI - Cryotherapy in infants with retinopathy of prematurity. A decision model for treating one or both eyes. AB - Formal decision model analysis for cryotherapy to reduce blindness from retinopathy of prematurity shows that the decision to treat depends substantially on disease severity, the probability of long-term side effects, and correlations of treatment outcomes and side effects for individuals in whom both eyes are treated. The model indicates that both eyes should be treated regardless of disease severity only when the probability of long-term side effects is zero. As risk of long-term side effects increase, treating neither eye or only the worst eye is preferred for an increasingly large spectrum of disease. With high correlations of long-term side effects, treating the worst eye is preferred for moderate levels of disease severity. For high disease severity, treating both eyes is recommended, even when the probability of long-term side effects is high. Better-informed treatment recommendations must await new data to assess risks of long-term side effects and correlations of treatment outcomes and side effects. PMID- 2918674 TI - Classification and analysis of fetal deaths in Massachusetts. AB - Fetal deaths, in contrast to infant deaths, have been subject to epidemiologic analysis infrequently. We characterized 574 Massachusetts resident fetal deaths from 1982 and assessed the accuracy of cause-of-death information available from vital records compared with that from corresponding fetal autopsies. The fetal death rate exceeded the neonatal mortality rate. Fetal mortality was higher among black, unmarried, and older mothers. Fetuses of multiple-gestation pregnancies had an unusually high risk of fetal death. Autopsy reports were obtained for 61% of fetal deaths. The underlying cause of death from the fetal death record differed from that on the autopsy report in 55% of cases. Systematic collection of population-based autopsy data is a useful approach for improving the quality and accuracy of mortality statistics on fetal deaths. Many stillbirths remain unexplained, however, and research is needed to identify pathological markers that might reduce the heterogeneity within the fetal deaths currently ascribed to unknown causes. PMID- 2918676 TI - Congenital syphilis and necrotizing funisitis. AB - During the past 5 years we encountered 16 cases of necrotizing funisitis, a deeply seated inflammatory process within the matrix of the umbilical cord, and established that all of them were associated with maternal and congenital syphilis. During that time necrotizing funisitis was not found to be associated with any other infection. The relationship was unexpected on the basis of current knowledge of the condition, but we found the older medical literature documents syphilis as the virtually specific cause of deep funisitis with angiophlebitis. Necrotizing funisitis has a characteristic macroscopic appearance, the "barberpole" cord, that permits the presumptive diagnosis of congenital syphilis at the time of birth. PMID- 2918675 TI - Mortality in infants discharged from neonatal intensive care units in Georgia. AB - Although neonatal intensive care units (NICUs) have contributed to advances in neonatal survival, little is known about the epidemiology of deaths that occur after NICU discharge. To determine mortality rates following NICU discharge, we used linked birth, death, and NICU records for infants born to Georgia residents from 1980 through 1982 and who were admitted to NICUs participating in the state's perinatal care network. Infants who died after discharge (n = 120) had a median duration of NICU hospitalization of 20 days (range, 1 to 148 days) and a median birth weight of 1983 g (range, 793 to 5159 g). The postdischarge mortality rate was 22.7 per 1000 NICU discharges. This rate is more than five times the overall postneonatal mortality rate for Georgia from 1980 to 1982. The most common causes of death were congenital heart disease (23%), sudden infant death syndrome (21%), and infection (13%). Demographic characteristics commonly associated with infant mortality were not strongly associated with the mortality following NICU discharge. PMID- 2918678 TI - A piece of my mind. At Nisqually. PMID- 2918677 TI - Implications of research and high technology for neonatal intensive care. PMID- 2918679 TI - Physicians' obligations under the National Childhood Vaccine Injury Act. PMID- 2918680 TI - Enterohepatitis in Mongolian gerbils (Meriones unguiculatus) inoculated perorally with Tyzzer's organism (Bacillus piliformis). AB - Enterohepatitis was produced in Mongolian gerbils by intragastric inoculation with Tyzzer's organism from natural infection of a gerbil. Death occurred in 50 to 60% animals 5 to 7 days postinoculation (p.i.). On day 3 p.i., when a few necrotic foci appeared in the liver, a large amount of bacterial antigen was present within ileocecal enterocytes and reticuloendothelial cells of the Peyer's patches. Neutrophil and monocyte infiltration was found in the lamina propria. On day 5 or 6 p.i. there was severe necrotizing and hemorrhagic ileotyphlocolitis. Bacterial antigen was abundant within not only enterocytes, but also smooth muscle cells of the ileum and jejunum as well as reticular cells of the mesenteric lymph nodes. On day 7 p.i. the intestinal lesions subsided in the presence of fewer bacteria, while necrotizing hepatitis became well developed. The results indicated that Mongolian gerbils were highly susceptible to the oral route of infection with the Tyzzer's organism. PMID- 2918681 TI - Chronic instrumentation and longterm investigation in the fetal and maternal baboon: tether system, conditioning procedures and surgical techniques. AB - A tether system, conditioning procedures and surgical techniques were designed to maintain chronic catheters and electrodes in the pregnant baboon and her fetus. The tether system was comprised of a lightweight metal backpack containing catheters and electrodes, couplers, pressure transducers and electrical cabling. The backpack was held snugly in place by shoulder and body straps. A flexible metal tether connected the pack to a ball bearing assembly mounted on the top of the animal's home cage. Attached to the assembly were two infusion pumps, fluid reservoir and slip ring electrical connector. The entire system rotated freely with the movements of the animal; thus, the instrumentation and connectors were secure while access was maintained for continuous physiologic recording and intravascular infusion or intermittent blood sampling with minimal physical restraint. Animals were conditioned to accept the system prior to pregnancy and animals who demonstrated tolerance were bred. An initial group of 10 pregnant animals were sham tethered during pregnancy at 102 +/- 7 days with term gestation estimated at 180 days. Surgical procedures were done at 136 +/- 4 days with placement of catheters in the maternal femoral artery and vein, fetal carotid artery jugular vein and trachea, amniotic fluid cavity, and electrodes for fetal electrocardiogram and electroencephalogram. The mean fetal survival time was 9.3 (range 0 to 29) days. The major complications which led to early delivery were placental abruption and rupture of amniotic membranes. With ultrasonic localization of the placenta and determination of fetal position before surgery, these complications may be avoided.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918682 TI - A steady state method of measuring carbon monoxide diffusing capacity of the lung of sheep. AB - A method for measuring the diffusing capacity of the lung for carbon monoxide (DLCO) in sheep was developed. The test's usefulness and reliability was studied in ten, splenectomized adult ewes. Hemoglobin concentration and weight were found to affect sheep DLCO. This article describes a method of determining DLCO in sheep, gives preliminary results of limited testing, and discusses factors affecting DLCO in sheep. PMID- 2918683 TI - Cardiopulmonary responses to Pseudomonas septicemia in swine: an improved model of the adult respiratory distress syndrome. AB - Bacteremia with resultant damage to multiple organ systems remains a serious problem in intensive care of human patients. We have developed a clinically relevant swine model of sepsis-induced adult respiratory distress syndrome (ARDS). Twenty-three animals were given various doses of Pseudomonas aeruginosa intravenously. Low cardiac output septic shock was prevented with massive fluid infusion. It was found that a dose of 1.0 X 10(7) colony forming units per 20 kg/min for 2 hours reliably produced respiratory failure in a setting of hyperdynamic sepsis which meets the diagnostic criteria of human ARDS. PMID- 2918684 TI - A comparison of experimental visceral leishmaniasis in the opossum, armadillo and ferret. AB - Visceral leishmaniasis is a severe, chronic protozoal disease of humans and animals. Although chemotherapeutic agents are available for the treatment of this disease, problems such as drug toxicity, drug ineffectiveness and drug resistance of the parasite are responsible for treatment failures. To determine whether a drug is a potential antileishmanial agent, screening tests are performed using in vitro and in vivo models. Subsequently, a study using an appropriate animal model is performed to clearly determine the efficacy of a drug against Leishmania. Due to current public concerns regarding the use of companion animals in addition to the high costs of obtaining and maintaining these animals for research use, conventional animal models used in these chemotherapy studies, notably the dog and monkey, are becoming less acceptable. Therefore, new, less expensive and more accessible animal models are needed for the study of antileishmanial compounds. In this study, the armadillo, ferret and opossum were evaluated as possible new animal models for visceral leishmaniasis. The marked body weight loss, hepatomegaly, splenomegaly, large amastigote densities and the microscopic lesions observed in the infected opossums indicated that the opossum was more susceptible to visceral leishmaniasis than the armadillo or ferret. PMID- 2918685 TI - Chlorine dioxide sterilization of implanted right atrial catheters in rabbits. AB - The disinfection of right atrial catheters in situ using chlorine dioxide was investigated. Catheters were implanted into rabbits (Oryctolagus cuniculi) and colonized by inoculation of Staphylococcus aureus, Sa-80, into the lumen. All of the catheters were colonized and the difference in numbers of bacteria recovered from animals destined for the control and disinfection groups was not significant. Animals were assigned randomly to the control or disinfection group. Treatment consisted of filling the catheter lumen of the disinfection group with chlorine dioxide and of the control group with sterile physiological saline daily for 15 minutes. In addition, both groups received systemic antimicrobial therapy. Cultures of blood withdrawn from the catheters and by venipuncture were negative for five of the nine control group animals after treatment for 5 days. Four control group catheters failed, after from 3 to 21 treatments, without ever achieving negative cultures. All nine animals in the disinfection group had negative cultures after treatment for 5 days. Subsequently, one animal from each group reverted to positive cultures. All nine control group catheters failed during the study, compared to only three disinfection group catheters (p less than 0.01). At necropsy, culture of cardiac blood, thrombi and catheter tubing sections demonstrated colonization of six in the control group and only one in the disinfection group (p less than 0.05). Rabbits tolerated the chlorine dioxide disinfection well and no adverse signs were noted. PMID- 2918686 TI - Effects of a commercial malathion dip preparation on the cellular and humoral immune response of BALB/c mice. AB - Because of the widespread use of malathion as a treatment for ectoparasitism, a study was undertaken to determine the effects of a malathion dip preparation on the BALB/c mouse immune system. Mice were treated with either 2% (recommended dosage) or 8% solutions of malathion or a water control. The cellular immune response was evaluated by in vitro exposure of lymphocytes to mitogens, and the humoral immune response was assessed by using an enzyme-linked immunosorbent assay (ELISA) to quantify antibody production against sheep red blood cells (SRBC). Responses to the mitogens and to the SRBC were not significantly different between 2% and 8% malathion treated and water treated mice. Results indicated that malathion did not affect these two aspects of the mouse immune system when used as a 2% or 8% dipping solution. PMID- 2918687 TI - A standard procedure for measuring rodent bedding particle size and dust content. AB - Hardwood dust can cause dermatitis, respiratory disease, allergies and nasal cancer in humans. A major concern with animal hardwood bedding is its dust content and its possible effects on animals and animal technicians. Previous reports on the quality control of rodent bedding did not specify sample size or shake time for measuring bedding particle size and dust content. These variables could alter particle size analyses. In an effort to more accurately characterize bedding particle size and dust content, 50g and 100g samples of hardwood bedding were shaken for 0.5, 1, 2, 3, 4, or 5 minutes in a portable sieve shaker containing U.S. standard sieves (Nos. 8, 20, 30 and 50) to determine optimum sample size and shake time. Significant differences (P less than 0.05 or greater) were observed in the percent of bedding retained on a No. 8 sieve when 50g and 100g samples were taken for 30 seconds or for 1 minute. Samples shaken for 2 or more minutes did not show any statistical differences in the percent of bedding which was retained on or passed through the different sieves. Major differences occurred in the percent of bedding which was retained or passed through the different sieves, when the shake time was varied from 0.5 to 5 minutes. These results indicated that 0.5 or 1 minute was definitely not enough time to accurately measure bedding particle size and dust content and that the sample size and shake time must be consistent in order to accurately compare the particle size and dust content of different shipments of bedding or to compare bedding from different vendors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918688 TI - Evaluation of dust respirators for elimination of mouse aeroallergens. AB - The efficiency of various dust respirators for eliminating mouse allergens [mouse urine proteins (MUP), pelts proteins (MPP) and serum albumin (MSA)] were evaluated with use of low-volume air samplers and immunochemical methods. Three kinds of dust respirators from one manufacturer which have different efficacy in the exclusion of dust particles were put on the fiber glass filter in each air sampler. Then the air in a mouse housing room was sampled. The allergens passed through the respirators, were trapped in the fiber glass filters, and then extracted from the filters. The allergens of MUP and MPP in the extract were measured by an inhibition method of fluorometric enzyme-linked immunosorbent assay (ELISA) for IgE antibody and those of MSA measured by a fluorometric sandwich ELISA. The respirator with the lowest capability of exclusion was found to eliminate 65-86% of respective allergens. The other two respirators with higher powers eliminated 98% of MUP. MPP and MSA were eliminated to undetectable levels through these respirators. This study provided a means for the evaluation of dust respirators for animal aeroallergens. PMID- 2918689 TI - A technique for liver biopsy in Pekin ducks. AB - The duck hepatitis B virus (DHBV), a member of the hepadna-virus group, has become a useful animal model for exploring important aspects in this family of viruses such as viral replication, course of infection, and the response to antiviral therapy. In chronically DHBV infected ducks, repeated analyses of liver tissue are important in defining the degree of viral replication and liver injury. We describe a technique for repeated liver biopsy using a Keyes skin punch biopsy. This technique provided sufficient quantities of liver tissue for serial analyses with minimal hemorrhage in 18 Pekin ducks. This procedure offers a safe and reliable method of obtaining serial liver biopsies. PMID- 2918690 TI - Pairing previously singly caged rhesus monkeys does not interfere with common research protocols. PMID- 2918691 TI - Spontaneous profuse superovulation in association with ectopic fetuses in a rabbit. PMID- 2918692 TI - Kinked tail in Sprague-Dawley rats. PMID- 2918693 TI - Otacariasis in tree shrews (Tupaia belangeri) caused by Criokeron quintus. PMID- 2918694 TI - South Carolina medical malpractice patients' compensation fund. PMID- 2918695 TI - JUA claims functions. PMID- 2918696 TI - The South Carolina Medical Association/Joint Underwriting Association risk management program. PMID- 2918697 TI - The SCHA Loss Control Program: reduction in liability exposures for hospitals and physicians. PMID- 2918698 TI - The South Carolina Dental Association and the S.C. Medical Malpractice JUA. PMID- 2918699 TI - Malpractice prophylaxis. PMID- 2918700 TI - So you are a defendant in a malpractice action. PMID- 2918701 TI - The deposition--the doctor, the lawyer. PMID- 2918702 TI - Quality assurance, quality management, risk management, and other buzz words of the eighties. How do we use them? PMID- 2918703 TI - Risk management. PMID- 2918704 TI - A proper balance. PMID- 2918705 TI - Constitutional Amendment One. PMID- 2918706 TI - South Carolina Medical Malpractice Joint Underwriting Association. PMID- 2918707 TI - Gamete intrafallopian transfer (GIFT): the South Carolina experience. PMID- 2918708 TI - Update on hospitalized pesticide poisonings in South Carolina, 1983-1987. AB - Three hundred twelve hospitalizations for pesticide poisoning occurred in South Carolina during 1983-1987. This represents a twenty percent decline from an average of 78.5 cases hospitalized per year (1979-1982) to 62.4 cases hospitalized per year currently. Non-occupational poisonings accounted for one half of the hospitalizations while 20% were related to occupation. Intentional poisonings represented 27% of the total. Two deaths as a result of suicide occurred during the four year period giving a case fatality of less than 1.0%. This five year update reenforces the need for continued education and prevention efforts. PMID- 2918709 TI - Chronic hepatitis and indolent cirrhosis due to methyldopa: the bottom of the iceberg? PMID- 2918711 TI - Beliefs, attitudes, and health promotion. PMID- 2918710 TI - Health promotion beliefs and attitudes of physicians: a survey of two communities in South Carolina. PMID- 2918712 TI - Slow poisons. PMID- 2918713 TI - Abdominal radiation causes bacterial translocation. AB - The purpose of this study was to determine if a single dose of radiation to the rat abdomen leads to bacterial translocation into the mesenteric lymph nodes (MLN). A second issue addressed was whether translocation correlates with anatomic damage to the mucosa. The radiated group (1100 cGy) which received anesthesia also was compared with a control group and a third group which received anesthesia alone but no abdominal radiation. Abdominal radiation lead to 100% positive cultures of MLN between 12 hr and 4 days postradiation. Bacterial translocation was almost nonexistent in the control and anesthesia group. Signs of inflammation and ulceration of the intestinal mucosa were not seen until Day 3 postradiation. Mucosal damage was maximal by Day 4. Bacterial translocation onto the MLN after a single dose of abdominal radiation was not apparently dependent on anatomical, histologic damage of the mucosa. PMID- 2918714 TI - Retarding liver cancer growth in the rat by transient repeated hepatic dearterialization. AB - The effect of repeated ischemic episodes to experimental liver tumors is studied in a group of inbred Wistar-Furth rats. A vascular occluder model was developed specially for the purpose of delivering intermittent compressions to the hepatic artery in the rat. With five daily 1-hr occlusions of the hepatic artery, rats benefited from significantly reduced tumor growth rates compared with controls that underwent sham operation (P less than 0.05). In contrast to results from previous pig experiments, it is demonstrated by angiographic studies that repeated transient dearterialization does not entirely overcome the problem of collateral vessel formation in the rat. Tumor neovascularization continues irrespective of whether the tumor is being dearterialized. It is also observed that in both normal and tumor rats, collateral channels from the left gastric artery temporarily open up when the hepatic artery is obstructed but disappear on reestablishment of flow. As such types of collateral flow are beyond our control, it is imperative that future developments in vascular occlusion therapy should aim at shortening ischemia time and combining with chemotherapy. PMID- 2918715 TI - The physiologic basis of the TUR syndrome. AB - To better assess the role of hyperammonemia versus hypoosmolarity versus hyponatremia in the TUR syndrome, we developed a rat model. Sprague-Dawley female rats received an intraperitoneal injection (250 cc/kg body weight) of either 1.5% glycine, 2.0% glycine, 2.0% glycine plus 1.5% mannitol, 3.0% mannitol, 5.0% mannitol, or 2.0% glycine plus 0.25% saline. Arterial blood samples were obtained prior to injection, at 2, 8, 16, and 24 hr and analyzed for osmolarity, sodium, and ammonia. Those animals receiving 2.0% glycine, 2.0% glycine plus 1.5% mannitol, and 5.0% mannitol all died within 24 hr with lethargy, convulsions, and coma. Hyponatremia developed in all animals; death, however, occurred only when the sodium concentration declined to 90-95 meq/dl. Mannitol maintained serum osmolarity but did not prevent coma and death. Including 0.25% saline in the initial injection, or an iv injection of 5.0% saline delayed 8 hr achieved 100% survival. Ammonia concentrations increased 15-fold by 8 hr in groups receiving 2.0% glycine; it rapidly decreased to near normal by 24 hr. Decreasing the rise in ammonia by 50% with iv arginine had no effect on survival. Our results suggest that hyponatremia rather than hyperammonemia or hypoosmolarity accounts for the major morbidity and mortality secondary to the TUR syndrome. PMID- 2918716 TI - Long-term nutritional function of orthotopic small bowel autotransplants. AB - Nutritional function following autografting of the entire small bowel was followed in 11 dogs for 12 months. Although positive nitrogen balance was recovered within a few weeks, the animals did not achieve their preoperative body weight for up to 6 months. Fat and D-xylose absorption remained depressed and never fully recovered. Hematocrit and serum iron did not normalize until the second postoperative month or later. Abnormal serum albumin and albumin/globulin ratio persisted for 12 months. When the mesenteric vein was anastomosed to the vena cava rather than to the portal vein, this group had more severe abnormalities in body weight, hematocrit, total protein, and serum albumin, in addition to a significant rise in liver enzymes. These findings represent a discouraging portent for the functional utility of small bowel transplants. PMID- 2918717 TI - The role of metal ions in ischemia/reperfusion injury in skin flaps. AB - The role of hydroxyl radical generation by the metal-catalyzed Haber-Weiss reaction in producing injury to postischemic skin flaps in rats was evaluated. The venous drainage from groin island flaps was occluded for 7 hr and then reperfused. The flaps were infused with either deferoxamine, CaNa2EDTA, histidine, salicylate, or vehicle (saline) at the time of reperfusion. In another experimental group, the role of hydrogen peroxide was evaluated by the infusion of catalase at the time of reperfusion. Treatment with a single dose of deferoxamine (40 mg/kg), CaNa2EDTA (50 mg/kg), or histidine (50 mg/kg), significantly increased the flap survival rate from 24 to 63, 75, and 63%, respectively. A large dose of salicylate (80 mg/kg) improved the flap survival rate (to 63%): a smaller dose (40 mg/kg) offered no improvement. A large dose of catalase ameliorated the survival rate (to 88%). The results suggest that the presence of metal ions is required for the expression of free radical-induced tissue damage. Hydrogen peroxide appears to be essential for the production of this injury. PMID- 2918718 TI - Modulation of proline and glucosamine incorporation into tissue repair cells by peritoneal macrophages. AB - The purpose of this study was to determine the patterns of [14C]proline and [14C]glucosamine incorporation by tissue repair cells (TRC) as modulated by postsurgical macrophages. Rabbits underwent a midline laparotomy followed by resection (2.0 cm) and reanastomosis of their ileum. Another group of rabbits underwent peritoneal wall abrasion with sterile gauze until punctate bleeding developed. Postoperative (1-28 days) exudate cells (PEC) were recovered from the peritoneal cavity after reanastomosis, and (TRC) were obtained directly from the injured peritoneal surface after abrasion. Since the postsurgical exudate was composed mainly of macrophages, we examined the effect of postsurgical macrophage spent media on the incorporation of [14C]proline, [14C]glucosamine, and [3H]thymidine by TRC. After 7 days of culture, Postsurgical Day 7 TRC were incubated with spent media from postsurgical PEC (greater than 90% macrophages). When TRC were cultured with macrophage-spent media, the number of TRC increased significantly compared to that of fresh medium-treated controls. The incorporation of [3H]thymidine by TRC was also enhanced by macrophage-spent media. The incorporation of [14C]proline and [14C]glucosamine by TRC was also enhanced when incubated with macrophage-spent medium. However, when data were expressed on a per cell basis, incorporation of [14C]proline and [14C]glucosamine by TRC cultured with macrophage-spent media was the same or less than that by cells incubated with fresh medium. These data suggest that the increase in incorporation of glucosamine and proline into connective tissue protein by postsurgical repair cells may be directly modulated by macrophages recruited in response to surgical injury and that this increase is due to the fibroproliferative effect of postsurgical macrophages. PMID- 2918719 TI - Sixty minutes of normothermic ischemia in the rat liver: correlation between adenine nucleotides and bile excretion. AB - The effect of 60 min of normothermic liver ischemia on cellular levels of adenine nucleotides (ATP, ADP, and AMP), energy charge (EC), and bile excretion was studied. Following ischemia the concentration of ATP was reduced to 12% of preischemic and control values within the first 10 min and remained low during the remaining ischemic period. EC values were also low. During 120 min of reperfusion, ATP increased to 34% of the ATP level found in the control group. EC values increased immediately to reach values not significantly different from those of control animals. Bile flow was nonexistent during ischemia and increased during reperfusion. The increase paralleled those of ATP and EC. Bile flow seems to reflect the degree of liver ischemia and may be used as a functional parameter. PMID- 2918720 TI - Clinical and histopathological appraisal of preoperative irradiation for adenocarcinoma of the pancreatoduodenal region. AB - A retrospective review to elucidate the rationale of preoperative irradiation was made on 18 carcinomas of the head of the pancreas area. After 50 Gy/25 fractions of 10 MV X-ray was given, all 18 tumors decreased from 3.3 +/- 0.8 cm to 2.0 +/- 0.7 cm. At the surgical operation, 16 patients (89%) received pancreatic resection, without operative death. Histologically, in 13 of these 16 cases, the population of severely degenerative cancer cells (SDCC) was more than 1/3 of all cancer cells, and SDCCs were likely to locate at the periphery (advancing point of carcinoma). These histological patterns were considered as favorable to improve the operative curability. However, in the remaining three cases, the SDCC population was less than 1/3. In addition, nonaffected (i.e., viable) cancer cells were detected at the periphery, and this is an extremely adverse condition for subsequent surgery. Chronic pancreatitis in the noncancerous area was present in these three cases, but not in the 13 cases. Therefore, the most significant factor that predicts the radioresistance especially at the periphery of the carcinoma was considered to be coexisting chronic pancreatitis. PMID- 2918721 TI - Sarcoma-180 cells are more sensitive to heat than are mouse normal tissues: esophagus, stomach, small intestine, large intestine, liver, spleen, and kidney. AB - Sensitivity of various mouse tissues to heat was determined using mouse sarcoma 180 (S-180) cells and normal tissues: esophagus, stomach, small intestine, large intestine, liver, spleen, and kidney. The in vitro succinate dehydrogenase inhibition (SDI) test was used. The succinate dehydrogenase (SD) activity of tissue fragments was assayed, following exposure to a temperature of 43 degrees C (heat treatment) or 37 degrees C (control) for 1, 2, 5, or 10 hr. The sensitivity to heat treatment was estimated by the percentage of SD activity of the heat treated cells, compared to that of the control cells. The decrease in SD activity following exposure to heat varied with the tissue. The SD activity decreased to a greater extent in the S-180 cells than in the normal tissues. In the normal tissues, the order of sensitivity to heat was stomach, spleen, large intestine, small intestine, esophagus, kidney and liver. These results show that hyperthermia is tissue selective, hence heat treatment of a malignant lesion should be carefully designed. PMID- 2918722 TI - Results of radiation therapy in early glottic carcinoma (T1, T2 N0). AB - Glottic carcinoma is curable by either surgery or radiotherapy. A total of 60 patients were treated by radiation alone at the Northern Israel Oncology Center, Rambam Medical Center, Haifa, between 1970 and 1980. Twenty-nine (48%) were classified as T1 N0 and 31 (52%) as T2 N0. All patients received radiotherapy primarily with curative intent, with surgery reserved for recurrences. The 5-year actuarial survival for all patients was 90% and actuarial disease-free survival was 95%. In ten patients (17%) there was local failure, and five of them were salvaged by surgery. There were no significant acute or long-term complications of radiation. Factors influencing treatment outcome (anterior commissures involvement, degree of differentiation, treatment volume, and technique of irradiation) and the occurrence of second primary malignancies are discussed. PMID- 2918723 TI - Use of a totally implantable drug delivery system in a university-affiliated community hospital. AB - We reviewed our experience at the Western Reserve Care System with totally implantable drug delivery systems (IDDS) in cancer patients with vascular access problems. Fifty-one ports were placed in 50 patients. Forty-nine of the IDDS were placed under local anesthesia. One patient developed a hemothorax during placement. Two catheters were removed because of infection. Two catheters found to be occluded responded to flushing with streptokinase. All catheters remained functional up to the time of treatment completion or of the patient's death. The low morbidity and high success rates of IDDS should encourage placement early in the course of chemotherapy. PMID- 2918724 TI - Limitations of flow cytometric DNA analysis for the diagnosis of bladder cancer. AB - Flow cytometric analysis was done on exfoliated urothelial cells from 11 control patients and 31 patients with transitional cell carcinoma: 9 grade I, 11 grade II, and 11 grade III. The determination of aneuploidy by DNA analysis did not provide identification of low-grade tumor cells. Other flow cytometric parameters of cellular change such as cell size, nuclear size, nuclear/cytoplasmic ratio, or cell refractivity may provide better identification of low-grade lesions. PMID- 2918725 TI - Megaprostheses in the treatment of primary malignant and metastatic tumors in the hip region. AB - Twenty patients with malignant bone tumors of the hip region were treated surgically by resection and reconstruction with an endoprosthesis. Histologic types included five primary bone tumors and 15 metastatic lesions. At review four primary bone tumor patients are still alive without evidence of disease. The length of the observation period varied from 26 to 104 months. Eleven patients with metastatic bone disease died. The average postsurgical survival time was 23 months. All patients were able to walk with or without a cane. Failure of an endoprosthesis occurred in one case. According to the Enneking Evaluation System 11 patients had a good and 9 a fair result. PMID- 2918726 TI - 18th annual UCLA symposium. Abstracts: Hematopoiesis. PMID- 2918728 TI - 18th annual UCLA symposium. Abstracts: Developmental biology. PMID- 2918727 TI - 18th annual UCLA symposium. Abstracts: Molecular biology of aging. PMID- 2918729 TI - 18th annual UCLA symposium. Abstracts: Defense molecules. PMID- 2918730 TI - 18th annual UCLA symposium. Abstracts: Molecular evolution. PMID- 2918731 TI - Transhiatal esophagectomy with gastric transposition for pharyngolaryngeal malignant disease. AB - Between 1981 and 1988, 41 patients underwent pharyngolaryngoesophagectomy with transhiatal gastric transposition and primary pharyngogastrostomy for hypopharyngeal, laryngeal, and cervical esophageal carcinoma. All patients had squamous cell carcinoma. Twenty-one patients had been treated initially by high dose radiotherapy, but the tumor had either persisted or recurred. Four patients had previously received high-dose local radiotherapy to the neck for unrelated diseases, and in 16 patients no preoperative radiotherapy was given. There was one operative death. Anastomotic leaks developed in nine previously irradiated patients and three required flap reconstructions. Thirty patients had satisfactory swallowing postoperatively and three swallowed poorly. Delayed gastric emptying was a serious problem in two patients, necessitating pyloric bag dilatation in one and pyloroplasty in another. The average postoperative stay was 31 days. Thirty-seven percent survived longer than 12 months and 15% longer than 24 months. The probability of survival after 2 years is 35%. All deaths from recurrent disease occurred within 412 days postoperatively. At present, pharyngolaryngoesophagectomy with gastric transposition and primary pharyngogastric anastomosis offers the best chance for cure or palliation with acceptable morbidity and function for selected patients with advanced hypopharyngeal and laryngeal tumors. PMID- 2918733 TI - The current status of surgery for bullous emphysema. AB - The great majority of cases of emphysema are generalized with diffuse involvement of all portions of the lung: Clearly, surgery has little to offer in such cases. In contrast, there is an uncommon variant involving primarily the upper lobes and the superior portions of the lingula and lower lobes, which spares the relatively normally functioning lower lobes. A number of diagnostic tests are available to identify compression of uninvolved lower lobe tissue, the most reliable of which identify pulmonary vasculature that is crowded together. We suggest that whole lung tomograms or pulmonary angiograms provide the most convincing evidence of compression of normal tissue. In properly selected patients with compression or displacement of normal lung, thoracotomy with simple excision of the bullae is tolerated by even the most ill patients if care is taken to carefully support the patient postoperatively with assisted ventilation and prolonged chest tube suction. There were no deaths in 19 patients and the results were rewarding, often spectacular, and surprisingly enduring. It is likely that some patients with operable bullous emphysema are not being studied or offered operation because of a lack of knowledge about the benefits possible with bullectomy. PMID- 2918734 TI - Reinforced staple line in severely emphysematous lungs. AB - In severely emphysematous or otherwise destroyed lung parenchyma, staples often cut through, which causes prolonged postoperative air leakage. A mechanical suture line reinforced by a polydioxanone ribbon is a simple, safe, and effective method for closure of air leaks, resection, or biopsy in such cases. PMID- 2918732 TI - Urgent operation for acute transverse aortic arch dissection. AB - Surgical intervention is generally accepted for acute type A dissection, but little is published regarding therapy for acute dissection of the transverse portion of the aortic arch, though involved in approximately 15% of cases. Often, surgical treatment is withheld if aortography suggests a primary tear in the aortic arch. Similarly, resection is limited to the ascending aorta despite intimal tears within the transverse portion of the arch. This work reports a 9 year experience with a policy of emergency resection for all acute aortic dissections involving the aortic arch. Intensive "antiimpulse" therapy is instituted and aortic angiograms are obtained. Type A dissections are resected under moderate hypothermia and, if the primary tear extends into the arch or is not found in the ascending aorta, the arch is explored during a brief period of deep hypothermia and circulatory arrest. If necessary, the arch is replaced during circulatory arrest, the patient's head is packed in ice, steroids are administered, and a barbiturate coma is induced. If arch replacement is anticipated preoperatively, surface cooling is also employed. Sixteen acute (up to 14 days) and three subacute (15 to 28 days) transverse arch dissections were treated in this manner between May 1979 and May 1988, with four (21%) hospital deaths (25%, acute; 0%, subacute). Mortality was related to left main coronary dissection with extensive myocardial infarction in two of our four cases, a third death was related to persistent seizures in a renal transplant patient requiring hemodialysis who had lupus cerebritis, and the fourth resulted from rupture of the descending aorta 15 days after arch replacement.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918735 TI - Blood platelets in cardiopulmonary bypass operations. Recovery occurs after initial stimulation, rather than continual activation. AB - The ultrastructure of blood platelets was related to platelet function and secretion products before, during, and after cardiopulmonary bypass. Circulating platelets from 15 patients undergoing aorta-coronary bypass operations were investigated at ten predetermined points of time by scanning and transmission electron microscopy. Simultaneously, platelet adenosine triphosphate, diphosphate, and serotonin, as well as plasma levels of platelet factor 4, beta thromboglobulin, serotonin, thromboxane B2, lactic dehydrogenase, and free hemoglobin were measured. Moreover, platelet responsiveness toward adenosine diphosphate and collagen was determined by optical aggregometry. By scanning electron microscopy, the number of unactivated platelets dropped from 96% +/- 4% to 54% +/- 19% (p less than 0.05) 8 minutes after the onset of bypass. Simultaneously, the percentage of "shape changed" platelets significantly increased. No major release reaction was detected at this time. After the initial activation, platelet morphology began to recover although the bypass continued. During the late period of bypass, a highly significant correlation between increasing plasma levels of alpha-granule compounds (platelet factor 4 and beta thromboglobulin) and lysis parameters (lactic dehydrogenase and free hemoglobin) was found. However, transmission electron microscopic analysis of the arterial filter and scanning electron microscopic findings of circulating platelets indicated that the release products in plasma were due not only to platelet lysis but also to a limited extent to secondary aggregation. In an inverse and probably causative manner, platelet morphology recovered, whereas the sensitivity of platelets to adenosine diphosphate and collagen decreased toward the end of bypass. PMID- 2918736 TI - Aortic atresia with normal left ventricle. Single-stage repair in the neonate. AB - Four to seven percent of infants born with aortic atresia have a normal-sized left ventricle in association with a ventricular septal defect and a normal mitral valve. In contrast to the more common group of infants with aortic atresia whose left ventricle is hypoplastic, this important subgroup has potential for complete operative correction involving both the right and left ventricles. Previous reports of surgical management of these infants have described early palliative procedures to control systemic and pulmonary blood flow. Our approach has been to perform complete repair at one stage in the neonate. Continuity between the proximal main pulmonary artery and aorta is established, a patch on the ventricular septal defect baffles left ventricular blood to the pulmonary valve, and a homograft conduit achieves right ventricular-pulmonary artery continuity. Three of four neonates who underwent single-stage repair were discharged from the hospital in good condition. Achieving a physiologically normal circulation simplifies the postoperative management of this condition and is to be preferred over neonatal palliation. PMID- 2918737 TI - The Hancock II porcine bioprosthesis. A preliminary report. AB - From May 1983 to July 1987 a total of 153 Hancock II porcine bioprostheses have been implanted in 130 patients with a mean age of 59 +/- 8 years (range 29 to 76 years). Mitral valve replacement was performed in 72 patients, aortic valve replacement in 35, and mitral-aortic valve replacement in 23. Cumulative follow up of 121 survivors is 223 patient-years and 100% complete (range 0.4 to 4.5 years). The actuarial survival rate at 4 years is 88% +/- 8% for mitral, 86% +/- 7.8% for aortic, and 84% +/- 8% for mitral-aortic valve replacement. Minor thomboembolism occurred in two patients (0.9% +/- 0.6%/pt-yr) with an actuarial freedom from emboli at 4 years of 100% for mitral, 96% +/- 3.7% for aortic, and 91% +/- 8.6% for mitral-aortic valve replacement. Anticoagulant-related hemorrhage occurred in 10 patients (4.4% +/- 1.4%/pt-yr) with an actuarial freedom at 4 years of 90% +/- 4.8% for mitral, 89% +/- 5.8% for aortic, and 84% +/- 10.6% for mitral-aortic valve replacement. Failure of the porcine bioprosthesis was observed in three patients with an actuarial freedom at 4 years of 96% +/- 3.6% for aortic, 91% +/- 8% for mitral, and 91% +/- 8.6% for mitral aortic valve replacement. Actuarial freedom from all porcine bioprosthesis related complications at 4 years is 85.7% +/- 6.6% for aortic, 79% +/- 9% for mitral, and 70% +/- 13% for mitral-aortic valve replacement. No instances of primary tissue failure occurred.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918738 TI - Extended operation for lung cancer invading the aortic arch and superior vena cava. AB - Extended operation for lung cancer and mediastinal carcinoma involving the aortic arch or superior vena cava was performed in six patients. In three patients with lung cancer invading the right side of the mediastinum, sleeve pneumonectomy (two patients) or sleeve lobectomy was followed by resection and reconstruction of the superior vena cava with ringed polytetrafluoroethylene grafts. One patient with squamous cell carcinoma and T4 N1 M0 disease was alive and free of disease more than 34 months after the operation. The other patients with adenocarcinoma (T4 N1 M0) and adenosquamous cell carcinoma (T4 N2 M0) died 18 and 5 months after the operation of systemic metastases. In two patients with invasion of lung cancer into the left side of the mediastinum, resection and reconstruction of the aortic arch and left common carotid artery were performed by a femoro-femoral bypass. These patients had adenocarcinoma (T4 N2 M0) and large cell carcinoma (T4 N1 M0) and died of systemic metastases and bleeding during reoperation 12 and 4 months after the initial operation. In one patient with mediastinal squamous cell carcinoma, resection and reconstruction of the aortic arch and left subclavian artery were performed by application of a temporary bypass graft between the ascending and descending aorta. This patient was alive and free of disease more than 17 months after the operation. PMID- 2918739 TI - Anastomotic narrowing after esophagogastrectomy with the EEA stapling device. AB - We studied a series of 176 patients undergoing esophageal resection with the aid of the EEA surgical stapling device (Auto Suture U.K. Limited, Great Britain) during a period of 7 1/2 years. A total of 160 patients (91%) were operated on for malignant disease. Operative death occurred in 15 patients (8.5%), and there were three anastomotic leaks (1.7%). The prevalence of dysphagia caused by both benign and malignant strictures after esophageal resection in which the EEA stapler was used was 17.4%. The rate of benign anastomotic narrowing in discharged patients was 12.5%. Anastomotic stricture resulting from recurrent tumor caused dysphagia in 6.2% of the patients undergoing resection for malignant disease. The highest rate of benign anastomotic narrowing occurred in patients who had undergone esophageal resection for benign, nondilatable strictures. In these patients, the prevalence of benign anastomotic narrowing was 37.5%, compared with 9.6% in the patients undergoing resection for malignant disease (p less than 0.001). An additional trend was noted: The smaller the stapling head used to construct the anastomosis, the higher the prevalence of benign anastomotic narrowing; however, a statistically significant difference could not be documented. Ninety-five percent of patients with benign anastomotic narrowings complained of dysphagia within the first 6 months after the operation; 79% of these patients required two or fewer dilatations to relieve the dysphagia. Dysphagia after esophageal resection with the aid of EEA stapler occurred in just over one of six patients. The usual cause of the dysphagia was benign anastomotic narrowing, which responds well to dilatation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918740 TI - Synchronously stimulated skeletal muscle graft for left ventricular assistance. Case report. AB - A 56-year-old man with chronic dilatation of the heart caused by cardiomyopathy (New York Heart Association functional class IV) was selected for cardiomyoplasty. The procedure was divided into two separate stages. In stage I the latissimus dorsi muscle was prepared for progressive stimulation. For this purpose two pacing leads were attached to the muscle, one at the proximal and the other at the distal end, and connected to a pulse-train generator, which was placed subcutaneously. A stimulation protocol was initiated in which the requirements of the latissimus dorsi muscle were periodically increased. In stage II the latissimus dorsi muscle was dissected to make a pedicle graft, which was introduced into the thorax and wrapped around the left ventricle. Pacing electrodes were sewn onto the pedicle graft in the same fashion as in stage I. Two sensing electrodes were fixed to the epicardium of the right ventricle, and the four leads were connected to a double-chambered pacemaker. Twelve days later, the pacemaker was programmed to a bipolar mode, VAT, and the latissimus dorsi muscle graft was synchronously stimulated in a 1:1 assist mode. The patient's status improved to New York Heart Association functional class II. Echocardiographic studies showed better contraction of the posterior wall of the left ventricle, as well as reduction in its diameters. Radioisotopic studies demonstrated a significant improvement in hemodynamic parameters. Cardiomyoplasty seems to be an alternative in those patients with severe cardiac insufficiency caused by cardiac dilation owing to cardiomyopathy. PMID- 2918741 TI - Experiments with a bowl of saline: the hidden risk of hypothermic-osmotic damage during topical cardiac cooling. AB - Some of the misconceptions in the application of cardiac hypothermia are that the temperature of cold normal saline solution is necessarily above 0 degrees C, cold saline solution and slush are relatively safe for living tissues, and normal saline will retain normal osmolality even if partially frozen. These postulates were examined in thermodynamic experiments that demonstrated three points: (1) The temperature of unfrozen saline solution may drop way below the freezing point. (2) When liquids and solid components of saline solution are separated, the components will become hypo-osmolar or hyperosmolar. (3) Ice chips and slush ice produced in the operating rooms may reach temperatures as low as -36 degrees C. We recommend that the possibility of these events should be taken into consideration whenever topical cardiac hypothermia is clinically applied. PMID- 2918742 TI - Blood platelets and bypass. PMID- 2918743 TI - Neonatal arterial switch operation complicated by intramural left coronary artery and treated by left internal mammary artery bypass graft. PMID- 2918744 TI - Double-outlet ventriculoarterial connection. PMID- 2918745 TI - Peristaltic versus syringe pumps for push-pull perfusion: tissue pathology and dopamine recovery in rat neostriatum. AB - The characteristics of performance were compared for two types of pump, peristaltic and infusion-withdrawal, commonly used for localized push-pull perfusion of brain tissue. Guide cannulae were stereotaxically implanted bilaterally in the caudate-putamen complex of the rat at homologous sites in the coronal plane. Consecutive 5.0 min push-pull perfusions were carried out simultaneously with one pump perfusing ipsilaterally while the other pump perfused the contralateral caudate nucleus. 3H-dopamine (DA) diluted with an artificial CSF was used as the radiotracer and was perfused at a rate of 25 microliters/min. Following the collection of 7-8 samples, the brain was fixed, removed, and histological sections taken through the sites of perfusion. Microscopic examination of the perfusion site showed that the circumscribed lesion at the tip of the cannula connected to either pump was generally indistinguishable. A comparison of the values of 3H-DA recovery in samples obtained with the peristaltic and infusion-withdrawal pumps demonstrated that: (1) the respective uptakes of the catecholamine into caudate tissue paralleled one another in most experiments, and (2) the content of 3H-DA in push-pull perfusates recovered from sample to sample varied independently of the pump used. Based on the results of histopathological examination and DA radioactivity values, it is concluded that the peristaltic pump as well as the syringe-driven push-pull pump can yield valid experimental observations which are comparable to one another. PMID- 2918746 TI - The voltage-clamp apparatus assisted by a 'current pump'. AB - A current pump is described, which is attached to the last stage of the 2 microelectrode voltage-clamp apparatus. Thus a voltage-to-current conversion independent of the impedance of the current microelectrode is obtained. In this way it is possible to pass relatively large currents through the current microelectrode and in the same time to have a stable negative feed-back system. PMID- 2918747 TI - Single-channel current simulation and recording using a photodiode as current generator. AB - A device which can generate rectangular currents in the picoampere range is described. The current generator is a photodiode connected to the head stage of a single-channel recording amplifier. The photodiode is activated by a light emitting diode controlled by a computer or any other current source. The device can transmit signals corresponding to simulated single-channel behaviour. Since the kinetic parameters of the simulation are known, the user can test the data acquisition and analysis system under conditions similar to those prevailing during recording from a biological membrane. This current generator can also be used for the tuning of patch-clamp amplifiers; rectangular currents generated by the photodiode allow the frequency response of the amplifier to be properly adjusted. PMID- 2918748 TI - A high-speed multichannel neural data acquisition system for IBM PC compatibles. AB - An inexpensive 32-channel data acquisition system has been constructed for use in acquiring neuroelectric data from a multiple element electrode array. Direct memory access (DMA) techniques allowed a maximum aggregate sampling rate of 652 ksamples/s, or 20.4 ksamples/s on 32 channels. The 8-bit analog-to-digital (A/D) conversion circuitry lies on a single plug-in card installed in an IBM PC compatible AT & T 6300 Plus personal computer, although the card may be used in an IBM PC with no reduction in sampling performance. Data have been taken from 32 points on the surface of the rat hippocampal slice preparation. Assembly language graphics routines permitted rapid display of raw and processed data. Signal processing routines can be executed and results can be displayed to provide rapid feedback to an experimenter. PMID- 2918749 TI - A homing procedure for studying spatial memory in immature and adult rodents. AB - In this procedure, subjects learn the spatial position of one hole out of many, that allows them to escape from a large open-field into their home cage. The arena is circular and can be rotated between trials so that no proximal landmark is permanently associated with the target hole. This task is thus similar to the Morris water maze procedure, since subjects must remember the position of the escape hole relative to extra-arena cues only. In addition it allows studying the importance of olfactory cues such as scent marks in or around a hole. Since the motivation is to reach home and the motor requirement is low, this task provides a useful alternative to the Morris place navigation task for studying spatial orientation in weanling or senescent rats. Examples are given showing that various behavioural parameters provide a good estimation as how subjects learn this task. PMID- 2918750 TI - An improved method for tail-flick testing with adjustment for tail-skin temperature. AB - The tail-skin temperature is an important factor in determining tail-flick latency to noxious radiant heat in rats and mice. A simple, non-invasive method for recording the tail-skin temperature during conventional tail-flick testing is described. The method is conveniently performed during conventional tail-flick testing. It does not require additional handling of the animals, and it is not stressful. The method utilizes a small-sized thermocouple which is brought in contact with the dorsal surface of the tail close to the area exposed to the radiant heat stimulus. A computer based system is used to record the temperature and control the tail-flick apparatus. Continuous monitoring of skin temperature showed that the temperature as measured 23 mm from the tip of the tail agreed well with skin temperature in the position where the beam was focused during tail flick testing (13 mm from the tip). The skin temperature closer to the base of the tail (100 mm from the tip) showed considerably more deviation from the temperature 13 mm from the tip. Temperature measurements close to the heated area gave a higher degree of correlation between recorded temperature and tail-flick latencies than did temperature measurements closer to the base of the tail. These results provide further support for the contention that tail-skin temperature is an important factor when assessing nociception by means of the tail-flick test, and demonstrate that the temperature should be measured as close to the heated area as possible. PMID- 2918751 TI - How synaptic noise may affect cross-correlations. AB - The relationship between a postsynaptic potential (the 'test PSP') and the profile of the cross-correlation that it produces in a repetitively discharging mammalian motoneuron, with and without synaptic noise, has been explored by computer stimulation. In a noiseless motoneuron the cross-correlation profile represents the first derivative of PSP shape except where 'shadowing' occurs (Eqn. 1a-c). When synaptic noise is present the relationship changes. When the amplitude of spike-like 'noise PSPs' occurring at regular intervals reaches a critical value (Eqn. 2), all threshold crossings involve noise PSPs. Under these circumstances termed 'just maximally effective synaptic noise', the cross correlation represents test PSP directly (Eqn. 3a). When the interval between noise PSPs is shortened the relationship reverts to the first differential (Eqn. 4a-c). If the amplitude of the noise PSPs is less than the critical value (Eqn. 5) the cross-correlation profile is represented in a complex way by a combination of the first derivative of the upper part and the direct representation of the lower part of the test PSP. The area of the cross-correlation peak above baseline provides the most reliable estimate of EPSP amplitude in a noiseless motoneuron (Eqn. 6a). This area may fall to half for the same triangular test EPSP in the presence of just maximally effective synaptic noise (Eqn. 7a). In general, the presence of synaptic noise leads to underestimation of EPSP amplitude. These general principles remain valid for physiological noise consisting of randomly occurring EPSPs and allow certain experimental findings in cat motoneurons to be understood. PMID- 2918752 TI - Determination of intracellular pH in the in vitro hippocampal slice preparation by transillumination spectrophotometry of neutral red. AB - A method is presented for measuring intracellular pH (pHi) spectrophotometrically in hippocampal slices using the pH dye indicator, Neutral red (NR). Measurements of pHi by NR were compared directly with the creatine kinase (CK) equilibrium method. Slices were bathed in artificial cerebrospinal fluid buffered with bicarbonate/CO2. Intracellular pH in hippocampal slices was found to be more alkaline (approximately 0.3 pH units) than buffer pH and far more alkaline (0.5 pH units) than extracellular pH. Resting intracellular alkalinity was observed by using both the NR and the CK equilibrium methods. The method may be useful for studies of pH regulation in intact functioning tissues in vitro where rapid and repeated measurements are necessary or where cell size precludes measurements with pH-sensitive microelectrodes. PMID- 2918753 TI - Capacitance compensation and bridge balance adjustment in intracellular recording from dendritic neurons. AB - Under most experimental conditions in intracellular recording, the proper adjustment of the amplifier is essential for the interpretation of the signals recorded from neurons. It is considered possible to accurately align the capacitance compensation and bridge balance adjustments of the amplifier simultaneously with the recording of membrane potential of an impaled cell if a number of conditions are met. In the strictest sense, these conditions are met only if: (1) the neuron is isopotential and if its electrical behavior can be adequately described using a single exponential decay constant, and if (2) that decay time constant is much longer than that of the microelectrode. These conditions cannot usually be satisfied. Because intracellular adjustment of capacitance compensation and bridge balance is necessary in many circumstances, it is desirable, to know whether any of the methods for performing these adjustments are accurate when used under less strict constraints, and to assess the nature and degree of the error that can be expected when the constraints are ignored. The results of computer simulations of a simple intracellular recording amplifier, microelectrode and a dendritic neuron model consisting of an isopotential cell and terminated finite equivalent cylinder representation of the dendrites are presented here. These studies show that the introduction of fast components of the response to intracellular current transients by the redistribution of applied charge in dendrite neurons may sometimes make it impossible to correctly apply the conventional methods of capacitance compensation and bridge balance. If the high-frequency response of the intracellular recording amplifier has sufficient fidelity, however, these adjustments can be made to a sufficient degree of accuracy using the response to sine wave calibration signals of varying frequency. PMID- 2918754 TI - A simple device for the reliable production of varnish-insulated, high-impedance tungsten microelectrodes. AB - The construction and operation of a simple device that produces varnish insulated, high-impedance tungsten microelectrodes for single-unit recording is described. In essence, the device operates as a high-voltage pulse generator whose output creates an arc between a fully insulated tungsten microelectrode and a polished counter-electrode. As a result, insulation is removed reliably and symmetrically from the microelectrode tip. The device is constructed with a minimal outlay of time, skill, and money. PMID- 2918755 TI - Chromosome abnormalities in B cell chronic lymphocytic leukemia and their clinical correlations. AB - Cytogenetic analysis was successfully performed on 31 of 40 patients with chronic B cell leukemia. Clonal abnormalities were seen in 16 patients using various culture methods. Fourteen of these had unstimulated cultures established of which 13 had the clonal abnormality. Trisomy 12 was observed in seven patients while a 14q32 translocation was present in four. Race, age, hemoglobin, WBC, percentage of lymphocytes and prolymphocytes in BM and PB, platelets, Smig, lymph node, spleen, liver, pattern of bone marrow infiltration, therapy free interval, and overall survival were all compared. Significant correlations between the presence of clonal abnormalities and prior therapy (p less than 0.005) and an increase in prolymphocytes in bone marrow (p = 0.05) and/or peripheral blood (p = 0.0014) were observed. PMID- 2918756 TI - Culture conditions in chronic lymphocytic leukemia: relationship to karyotype. PMID- 2918757 TI - Isochromosome 9q in acute lymphoblastic leukemia: a new non-random finding. AB - The presence of an isochromosome is commonly associated with late-stage disease and has rarely been reported at diagnosis in hematological malignancies. Five patients (two males and three females aged 3, 6, 13, 13, and 35 years) with an acquired i(9q) at diagnosis of acute lymphoblastic leukemia (ALL) are presented; in one case it was the sole karyotypic change. The patients presented in November or January, two in 1983/84, three in 1987/88. The latter were three of 100 unselected ALL cases referred over a three year period for cytogenetics and successfully karyotyped. Two had a prior history of pancytopenia. Features of high risk ALL in these patients included age over 10 years (three cases), leukocyte counts greater than 200 x 10(9)/liter (two cases) and pre-B immunological phenotype (two cases). All achieved remission on standard protocols. One patient is disease free over 4.5 years from diagnosis. One relapsed at 3.5 years and is well following a bone marrow transplant in second remission. Follow-up for the remaining three patients is between 9 and 11 months. Our findings indicate that i(9q) frequently with additional chromosome change is a feature of newly diagnosed ALL. PMID- 2918758 TI - Retroviral src gene expression in continuous marrow culture increases the self renewal capacity of multilineage hematopoietic stem cells. AB - To define the action of the retroviral src gene on hematopoietic stem cells, C57BL/6 x DBA/2 (B6D2F1) mouse long-term marrow cultures were infected at initiation with Moloney murine leukemia virus (MuLV) pseudotypes of src recombinant retroviruses with the src gene inserted in the env region of an amphotropic MuLV (src-Ampho), or in the gag region of Moloney MuLV (src-Mo). Other cultures were infected with Friend spleen focus-forming virus polycythemia inducing strain (SFFVp), Moloney MuLV, or amphotropic MuLV, or were uninfected controls. Harvested nonadherent cells were tested weekly for multilineage, granulocyte-erythroid-megakaryocyte macrophage (CFU-GEMM) colony formation in vitro in recombinant murine IL-3 and erythropoietin, and individual colonies were removed, split 1:2, with half of each replated for in vitro self-renewal and the other half examined morphologically for number of hematopoietic cellular lineages, or tested for release of MuLV and src virus. Cultures infected with src Ampho, src-Mo, or SFFVp demonstrated a significant increase in cumulative nonadherent cell and CFU-GEMM production. There was prolonged self-renewal over seven serial transfers of individual CFU-GEMM from src virus-infected cultures over seven serial transfers, and five of 61 individual colonies from the second or third generations contained detectable v-src gene sequences, but none released detectable src virus. Self-renewal of CFU-GEMM was similar to that with permanent IL-3-dependent cell line B6SUtA. In contrast, MuLV-infected or control uninfected cultures produced fewer cells, and self-renewal of CFU-GEMM did not exceed three generations. IL-3-dependent clonal hematopoietic progenitor cell lines, derived from each culture group, formed no detectable tumors in vivo; however, each released the original helper and/or transforming virus. Adherent cell lines, derived from src-Ampho-infected cultures released src virus and formed fibro sarcomas in vivo. The data support the conclusion that src-recombinant virus expression in long-term marrow cultures increases the self-renewal capacity of multilineage hematopoietic stem cells. PMID- 2918759 TI - Differentiation stage-specific expression of a gene during granulopoiesis. AB - Differential screening of a recombinant cDNA library using cDNAs transcribed from poly(A)+ RNA of normal or leukemic leukocytes revealed a number of recombinants homologous to mRNAs characteristic of particular leukemias. The occurrence of one of these (pCG14) in high abundance was shown to be sufficiently characteristic of the circulating leukocyte population of chronic granulocytic leukemia (CGL) patients to distinguish them from all other populations of leukocytes. We have now characterized the gene encoding this mRNA and shown that its expression is specific to the granulocyte lineage in hemopoietic cells and is, moreover, limited to a narrow stage of differentiation during granulopoiesis. Our results explain why high levels of pCG14 RNA are characteristic of chronic granulocytic leukemia peripheral blood leukocytes. PMID- 2918760 TI - Cytogenetic and molecular studies of the Philadelphia translocation t(9;22) observed in a patient with myelodysplastic syndrome. AB - We report here the case of a patient with refractory anemia with excess of blasts (RAEB) which evolved into RAEB in transformation. The standard Philadelphia (Ph) chromosome was found by cytogenetic study at diagnosis and during evolution. Southern blot analysis showed breakpoint cluster region (bcr) rearrangement as observed in chronic myelogenous leukemia (CML). PMID- 2918761 TI - "Cytoplasmic" expression of nuclear antigens. PMID- 2918762 TI - Which cells do respond during in vitro stimulation of B-CLL and HCL cultures? PMID- 2918763 TI - Outreach as case finding: its effect on enrollment in prenatal care. AB - One mechanism proposed for encouraging use of prenatal services in low-income communities involves the employment of community residents to encourage and support individuals in the use of available medical care. This study examines the effect of such workers on the start of prenatal care among a cohort of women receiving prenatal services at clinics affiliated with Harlem Hospital. Of the 599 women enrolling for prenatal care during the intake period for the study, only 52 had had an outreach contact before the start of prenatal care despite extensive field activity. No difference in the week of gestation at the start of prenatal care was noted between those with and without outreach contacts. Controlling for factors associated both with trimester of initiation of prenatal care in this population and with outreach contact did not account for this lack of difference. This type of outreach, known as case-finding, proved to be very labor intensive. Other less costly techniques for encouraging use of services in mobile, urban populations should be sought. PMID- 2918764 TI - The epidemiology of delays in a teaching hospital. The development and use of a tool that detects unnecessary hospital days. AB - This study's purpose was to develop a tool that detects, quantifies, and assigns causes for medically unnecessary hospital delays and use it to describe the epidemiology of delays at a teaching tertiary care hospital. Based on observational data, a taxonomy of delays was constructed that included nine major categories and 166 subcategories. This formed the basis for an instrument for detecting inefficiency in hospital care: the Delay Tool. Initially designed for real-time concurrent assessment, in retrospective use it was also reliable, requiring about 6 minutes per medical record. In using the Delay Tool over a 6 month period on general internal medical and gastrointestinal services, it was discovered that 30% of 960 patients experienced delays, the average length of which was 2.9 days. This represented 17% of all hospital days. The most frequent causes of delays were scheduling of tests (31%), unavailability of post-discharge facilities (18%), physician decision-making (13%), discharge planning (12%), and scheduling of surgery (12%). Because of the longer lengths of the delays involved with awaiting postdischarge facilities (primarily nursing home beds), this was the most important cause of delays and represented 41% of all delay days. The general medicine and gastrointestinal services had significantly different distributions of delay types related to their different kinds of patients and care. The Delay Tool should be helpful in addressing hospital, and hospital related, inefficiencies in health care delivery. PMID- 2918765 TI - Social support, stressful events, strain, dietary intake, and the elderly. AB - Little research exists linking social support, stressors, and related nutritional strain (loss of appetite) with the risk of poor nutritional health. Relationships among these concepts were investigated using a sample of elderly Virginians. It was hypothesized that the risk of poor nutritional health (dietary inadequacy) is reduced among elderly with high levels of social support and exacerbated among those experiencing stressful events and strain. Moreover, it was hypothesized that the negative effects of stressful events and strain on the diet are mitigated by high levels of social support. Using multiple regression models, these hypotheses were tested, controlling for age, sex, race, and socioeconomic status. The results indicated that elderly with 1) an extensive friendship network have more adequate diets; 2) greater financial stress experience greater nutritional stress (poorer appetite); and 3) greater nutritional stress have less adequate diets. Moreover, companionship serves as a buffer against the negative effects of poor appetite on dietary intake. PMID- 2918766 TI - Bug/drug resistance. Sometimes less is more. AB - Increased use of antibiotics in any community increases the risks that future bacterial strains will resist the effects of current antibiotics. The consequences of a resistant bacterial strain include costs for more expensive and powerful drugs, additional hospital days, and on rare occasion, death. A key to understanding the importance of this problem is better knowledge about the rate that resistance increases and persists as antibiotic use rates increase. Using the scant evidence available in the literature, this study conducts a sensitivity analysis to calculate the unrecognized costs of antibiotic use annually in the United States under various possible circumstances. For the estimated 150 million annual antibiotic prescriptions, the unrecognized costs appears to be at least $.1 billion, and they may exceed $30 billion in the worst case. The estimates of the burden caused by bacterial resistance to antibiotics depend heavily on unknown parameters, including the rate that resistance occurs, the dose resistance patterns through time, the frequency of inappropriate use of antibiotics, and the frequency with which death occurs due to a resistant bacterial infection. New studies in each of these areas are needed to improve our understanding of the extent of the resistance problem. PMID- 2918767 TI - Cardiovascular pharmacotherapy III. PMID- 2918768 TI - Government viewpoint of clinical trials of cardiovascular drugs. AB - The design of clinical trials affects their usefulness in evaluating the effectiveness and safety of drugs. Problems associated with active control studies are described and methods are given for effective dose-finding. The importance of dose-finding and dose-interval determination is emphasized. PMID- 2918769 TI - [Low frequency noise--an overlooked environmental factor]. PMID- 2918770 TI - [Estrogen or calcitonin in prevention of osteoporosis?]. PMID- 2918771 TI - [The validity of arterial gas analyses--storage temperature has negligible effect]. PMID- 2918772 TI - [Oral rehydration in acute diarrhea--a problem not only in developing countries]. PMID- 2918773 TI - [Campylobacter pylori--an amazing discovery still of current interest]. PMID- 2918774 TI - [Meeting of the association for medical angiology: how to manage atherosclerosis and treat peripheral vascular disease?]. PMID- 2918775 TI - [X-ray pictures via picture-telephone as a possibility for consulting physicians]. PMID- 2918776 TI - [Insufficient resources of clinics for adolescents for preventing chlamydia infections]. PMID- 2918777 TI - [The WHO program for the 21st century: campaigns for the eradication of diseases and health for all]. PMID- 2918778 TI - [Medical ethics. The ethical committees of the Swedish National Board of Health and Welfare and the Swedish Medical Society: refusal of blood transfusion should be respected if the patient is aware of the consequences]. PMID- 2918779 TI - [The fight against venereal diseases. A difficult balance between trust and community benefits]. PMID- 2918780 TI - [The scientific society and research fraud. Even the fraudbusters are attacked now]. PMID- 2918782 TI - [A notable decrease of hepatitis B in Stockholm and Gothenburg but not in Malmo Lund]. PMID- 2918781 TI - [Is it time for patient care regulation?]. PMID- 2918783 TI - [Roentgen is old-fashioned in the diagnosis of ulcerative colitis]. PMID- 2918784 TI - [The leadership responsibility and psychiatrists--legal views]. PMID- 2918785 TI - [Cardiology in Sweden--risk of unnecessary surgery?]. PMID- 2918786 TI - [Injury pattern among skiers during winter holidays in Skane]. PMID- 2918787 TI - [The number of children with abnormalities is not higher than expected in Soderhamn]. PMID- 2918788 TI - [Is electrodermal measurement a complement in assessing suicide risk?]. PMID- 2918789 TI - [Fibromyalgia--a new name for a syndrome with diffuse muscular disorders]. AB - This new name for an old and common disease has introduced fresh criteria and initiated clinical and basic research. The present clinical knowledge of the diagnosis and treatment is reviewed. Morphological and biochemical findings in the muscle of fibromyalgia patients have shown an unevenly distributed reduction of the oxygen tension. Hypoxia in the muscle sensitizes nociceptors, resulting in hyperalgesia with a diffuse distribution of pain symptoms. These are difficult for the individual to localize and are often combined with muscle stiffness and increased fatigability. These symptoms correspond to complaints received from fibromyalgia patients. PMID- 2918790 TI - [Chickenpox during pregnancy]. PMID- 2918791 TI - [Diseases of the motor system--a review]. PMID- 2918792 TI - [Intracranial hemorrhage--a too common adverse effect of anticoagulants?]. PMID- 2918793 TI - [Female alcoholics--psychopathology and treatment]. PMID- 2918794 TI - [Children in homes with alcohol problems--how do they feel and can they be helped?]. PMID- 2918795 TI - [Discitis in children--the natural history and presentation of 10 case reports]. PMID- 2918796 TI - [A comparative study of clinics: Terminal care personnel need communication, support and comfort to provide good care]. PMID- 2918797 TI - Speech tracking in the evaluation of a multichannel cochlear prosthesis. AB - Individual speech tracking data were analyzed in relation to other variables in 11 adult users of the Nucleus multichannel cochlear implant. Patients were categorized according to postoperative speech tracking results. The resultant groups could also be differentiated on the basis of postoperative MAC scores, surgeon's rating of overall success, and duration of deafness before implantation. The speech tracking paradigm appears to be a useful technique for the evaluation of performance with a cochlear prosthesis. PMID- 2918798 TI - Gadolinium-enhanced magnetic resonance imaging in temporal bone lesions. AB - A 2-year experience with an enhancement agent in magnetic resonance imaging (MRI) is examined through case presentations. Characteristics of the agent Gadolinium DTPA/Dimeglumin are reviewed. Radiographic capabilities in enhanced versus unenhanced MRI are compared. Temporal bone lesions, including acoustic neuromas and facial nerve neuromas, are presented. Recent experience with facial nerve enhancement in Bell's palsy is also presented. Greater accuracy in defining small temporal bone lesions and increased delineation of facial nerve involvement appear to be significant benefits with enhanced MRI. PMID- 2918799 TI - Functional endonasal sinus surgery (FESS) in the pediatric age group. AB - Functional endonasal sinus surgery has become a popular mode of surgical treatment for sinus disease in the United States. The literature has primarily addressed its use in the adult population. We present our series of 57 children who underwent functional endonasal sinus surgery. The children ranged in age from 3 to 15 years. Follow-up was from 3 to 13 months. Fifty-four of the patients were treated for chronic or recurrent sinus infections. Three patients were treated for complications of acute sinusitis. All patients tolerated the procedure well, and there were no major complications. We conclude that functional endonasal sinus surgery is a safe procedure in the pediatric age group. Although postoperative follow-up in the series was very short, early results appear encouraging. The technical approach is similar to that used in the adult procedure. The pediatric procedure, however, requires a follow-up nasal endoscopy under general anesthesia to achieve optimal results. PMID- 2918800 TI - Synchronous facial vascular vasodilation and salivatory response to atropine in the parasympathetically denervated human salivary parotid gland. AB - Hypersalivation and facial skin hyperemia that simultaneously emerge in response to atropinization have been observed in patients who suffered trauma to the skull base combined with damage of the parasympathetic secretory and vasodilatory fibers in the greater and lesser petrosal nerves at the tip of the temporal bone pyramid. The study was facilitated by special vacuum capsules applied to both outlet ducts of the parotid glands. Hyperemia and hyperthermia of the face were evaluated visually, by thermometer readings, and color photography. The events described are distinct from those reported in the literature (i.e., paradoxical disturbances of facial and salivary gland innervation). This study analyzes the mechanism of initiation and the manifestations of this complex syndrome. PMID- 2918801 TI - Normal brainstem auditory evoked potentials in adult hypothyroidism. AB - Nervous system dysfunction and hearing loss are part of the clinical picture of hypothyroidism. Several studies on visual evoked potential and two brainstem auditory evoked potential studies have shown abnormalities in this disease that are reversible with treatment. It has been suggested that visual evoked potential and brainstem auditory evoked potential could be useful to evaluate the effects of hypothyroidism on the central nervous system and to monitor the response to treatment. We recorded brainstem auditory evoked potentials in 15 adult hypothyroid patients immediately before treatment. All patients were women, ranging in age from 34 to 82 years. Fourteen also had an audiometric study. In five patients, both tests were repeated 20 to 22 months after treatment. Audiometry showed that hearing loss increased with age, suggesting that hearing loss in these patients could be secondary more to aging than to hypothyroidism. When compared to sex-matched controls of similar ages, our patients showed no statistically significant differences in brainstem auditory evoked potentials before treatment. Brainstem auditory evoked potential values were not modified in the five patients whose tests were repeated after treatment. The normality of these results raises serious objections to the clinical use of brainstem auditory evoked potential for central nervous system evaluation and therapy monitoring in adult hypothyroidism. PMID- 2918802 TI - A new surface electrode for recording from the posterior cricoarytenoid muscle. AB - A new pharyngeal surface electrode for recording posterior cricoarytenoid muscle activity through the hypopharyngeal mucosa has been evaluated. The electrode was passed through one nasal passage into the hypopharynx. Correct electrode location was verified by increased activity during inhalation, with decreased activity during phonation. The procedure was evaluated in 45 subjects, 10 normal speakers and 35 patients with dysphonia. Accurate recordings were obtained in 25 subjects (56%). Problems encountered were lack of pharyngeal descent, electrode dysfunction, and signal interference due to phonatory vibration or interarytenoid activity. Signal validity was evaluated in four normal speakers with accurate electrode placement. Significant (p less than or equal to 0.001) increases in PCA activity occurred during tasks requiring vocal fold abduction. The electrode proved to be a useful, noninvasive clinical tool for recording PCA activity in some patients. PMID- 2918803 TI - Brainstem auditory evoked potentials with increased stimulus rate in patients suffering from systemic lupus erythematosus. AB - Central nervous system involvement in systemic lupus erythematosus is frequently occult, may be the presenting sign, and is a bad prognostic indicator. At present, there is no reliable, sensitive laboratory test for the evaluation and diagnosis of subclinical central nervous system involvement of the disease. Brainstem auditory evoked potentials with and without increased stimulus rate have been used to diagnose ischemic lesions in the central nervous system. Brainstem auditory evoked potentials, with and without increased stimulus rate, was used to investigate 15 systemic lupus erythematosus patients, 20 normal participants, and 5 patients receiving corticosteroids for bronchial asthma. A significant statistical difference was found in the net effect of increased stimulus rate in comparisons of the systemic lupus erythematosus patients with the normal group. Brainstem auditory evoked potentials, with increased stimulus rate, demonstrated subclinical involvement of the central nervous system in systemic lupus erythematosus, reinforcing the notion that increased stimulus rate measures are sensitive to ischemic changes, in this case, even in neurologically asymptomatic patients. PMID- 2918804 TI - Toy weapons and firecrackers: a source of hearing loss. AB - Although acoustic injury as a result of exposure to noisy toys and firecrackers has been reported previously, most of these studies have been conducted on adults. The purpose of this prospective study, conducted at the time of Deepawali, an Indian festival of fireworks, was two-fold: 1. to measure the acoustic output of representative samples of toy weapons and firecrackers and the intensity level at critical spectator points from the site of emission; and 2. to determine the auditory status of a cross section of the target population, involving 600 participants from various age groups, before and after exposure to firecracker noise at Deepawali. The average sound level at a distance of 3 m was 150 dB, thus exceeding the damage risk criterion for adults (i.e., 130 dB peak level). An average 30 dB persistent sensorineural hearing loss was found in 2.5% of the target population as a result of toy weapon/firecracker noise during Deepawali. The 9- to 15-year-old age group was most affected. A judicious approach in the manufacture and use of toy weapons and firecrackers, in addition to legal restraints, is advocated. PMID- 2918805 TI - Intentionally induced abnormalities in optokinetic pattern tests. AB - Abnormalities of optokinetic nystagmus are easily detected by administering an optokinetic pattern test, in which optokinetic nystagmus responses to acceleration and deceleration of a series of optokinetic stimuli are recorded at slow paper speed, and the results are visually assessed based on the response pattern. Although optokinetic pattern tests are regarded as valuable in diagnosing lesions of the nervous system that directly or indirectly relate to the reflex route of optokinetic nystagmus, these tests can be significantly influenced by the intention of the person being tested. The present study revealed that the majority of abnormal optokinetic patterns can be induced intentionally. This indicates that optokinetic pattern tests are of limited diagnostic value, and a definite diagnosis should not be made based solely on the optokinetic pattern test result. PMID- 2918806 TI - The pleural osteomuscular flap in oropharyngeal reconstruction. AB - The addition of a pleural segment to the osteomyocutaneous flap used in head and neck reconstruction can be efficacious in selected cases. The pleura underlying the rib segment has been shown to remain viable and provide good healing and oral lining. The extent of pleura that can be transferred is unknown and currently being investigated, but pleura can be safely taken to the edges of the superior and inferior ribs. The pleura offers a thin, pliable, reconstructed surface to the oral cavity that alleviates bulky flaps or difficulty with intraoral skin grafts. This adaptation is a valuable addition to the surgeon in head and neck reconstruction. PMID- 2918807 TI - Coaxial frontal sinus drainage catheter. PMID- 2918808 TI - Intraoral approach to rigid internal fixation of anterior mandibular fractures. PMID- 2918809 TI - Diagnostic endoscopy of the pediatric airway. PMID- 2918810 TI - Middle ear pressure changes after general anesthesia. PMID- 2918811 TI - Mohs micrographic surgery. PMID- 2918812 TI - Methods for depleting brain glutathione. AB - To search for a technique to deplete reduced glutathione (GSH) in brain, the influence of various types of compounds on brain GSH levels was investigated in mice. Of the compounds tested, cyclohexene-1-one, cycloheptene-1-one and diethyl maleate were shown to be potent GSH depletors in brain as well as in liver. The depletion of cerebral GSH ranged about 40-60% of control levels at 1 and 3 hr after intraperitoneal injection. Cyclohexene, cycloheptene, phorone, acetaminophen, and benzyl chloride caused mild depletion of cerebral GSH, but buthionine sulfoximine did not alter cerebral GSH levels. Further, intracerebroventricular injection of cyclohexene-1-one and cycloheptene-1-one caused depletion of brain GSH to about 60-80% of control levels at 1 hr after injection, and the effects persisted for at least 6 hr. Under these conditions, hepatic GSH was not altered. These results demonstrated that cyclohexene-1-one and cycloheptene-1-one can cause not only a marked depletion of brain GSH by systemic administration, but also depletion of cerebral GSH by intracerebroventricular injection by virtue of being water-soluble compounds. Thus, methods for depleting brain GSH employing both compounds are available for exploring possible functions of cerebral GSH in in vivo systems. PMID- 2918813 TI - Hepatic metastases: rat models for imaging research. AB - Improved rat liver tumor models with solitary or multiple metastatic tumors were developed for radiological imaging research. Unlike previous studies which employed trocar inoculation of tumor fragments, an enzymatically disaggregated cell suspension of mammary cancer was injected by fine needle either directly into the liver to produce solitary cancer nodules, or indirectly via the spleen or mesenteric vein to produce multiple liver metastases. Tumor size was proportional to the time elapsed after implantation. The operative mortality of direct liver, splenic parenchymal, and mesenteric inoculations were 8%, 4%, and 27%, respectively. MR tissue characteristics, image contrast, and pharmaceutical enhancement of these tumors closely resembles human hepatic metastases. The availability of reproducible, inexpensive animal models of metastatic cancer allows efficient evaluation of new liver imaging techniques. PMID- 2918814 TI - Reduced blood flow in the transverse sinus visualized by ultra low field magnetic resonance imaging. AB - With an ultra low field magnetic resonance imager (ULF-MRI) operating at 0.02 Tesla we describe a case of increased signal intensity from the transverse and sigmoid sinuses of the brain. A comparison with radionuclide angiography and skull computer tomography is made. The difficulties in differentiating low blood flow and venous thrombosis is also discussed. PMID- 2918815 TI - Quantitative magnetic resonance imaging of vertebral bodies: a T1 and T2 study. AB - Multiple point T1 and T2 values of 424 vertebral bodies were measured and analysed. The influence of several factors including age, sex, location in the spine and status of neighbouring discs on the measured relaxation times were evaluated. The results indicate limitations in the region of interest approach. Vertebral bodies of different age, sex and location in the spine could not be distinguished. For heterogeneous tissues a more advanced form of image analysis appears to be essential. Diurnal factors resulting from the stress of normal ambulatory activity caused increased variation in vertebral body relaxation time values. PMID- 2918816 TI - Thermoregulatory consequences of cardiovascular impairment during NMR imaging in warm/humid environments. AB - A simple model of physiological thermoregulation, previously adapted to predict the thermoregulatory consequences of exposure to the nuclear magnetic resonance (NMR) imaging environment, has been further adapted to simulate impaired cardiovascular function. Restrictions on the rate of skin blood flow (SkBF), ranging from 0 to 89% of normal, were studied. Predictions of physiological heat loss responses in real time were generated as a function of ambient temperature (Ta), relative humidity (RH) and rate of whole-body radiofrequency (RF) energy deposition (SAR). Under conditions that are desirable in the clinic (Ta = 20 degrees C, 50% RH, still air), moderate restrictions (up to 67%) of SkBF yield tolerable increases in core temperature (delta Tco less than or equal to 1 degree C) during NMR exposures (SAR less than or equal to 4 W/kg) of 40 min or less. Increased Ta and RH exacerbate the thermal stress imposed by absorbed RF energy; severely impaired SkBF encourages short NMR exposures (e.g., 20 min or less) at SARs less than or equal to 3 W/kg. In warm/humid environments, sweating is predicted to be profuse and evaporative cooling curtailed, yielding a state of extreme thermal discomfort. Added insulation (e.g., a blanket) is discouraged. Some guidelines, incorporating SkBF restrictions, Ta, RH, and insulation, are offered for the prediction of tolerable NMR exposure conditions. PMID- 2918817 TI - Marrow infarction in sickle cell anemia: correlation with marrow type and distribution by MRI. AB - Ischemic necrosis of bone is believed to occur exclusively in areas of predominantly fatty marrow. Sickle cell disease is unusual in that marrow infarction occurs in areas of active hematopoiesis. MR images of long bone obtained in ten patients with sickle cell anemia (SCA) were analyzed to correlate the distribution and appearance of marrow infarction with the type of marrow. While the hematopoietic marrow predominated in metaphyseal and diaphyseal regions of femurs and tibias, the fatty or mixed marrow was the most common pattern in epiphyses. Infarcts occurred in fatty as well as hematopoietic marrow. Marrow infarcts were isointense or minimally hyperintense on T1 weighted images with the hematopoietic marrow and therefore difficult to detect. On T2 weighted images, the infarcts showed very high signal. T2 weighted images are essential for detection of marrow infarction. Soft tissue changes seen as low signal on T1 and high signal on T2, may be secondary to intramuscular injections of analgesics or muscle ischemia occurring during sickle crisis. PMID- 2918818 TI - Vascular morphology by three-dimensional magnetic resonance imaging. AB - A three-dimensional examination of blood vessels is provided using MR data from seven cases. The vascular surfaces are constructed with an algorithm that automatically follows the selected artery or vein and generates a projected three dimensional gradient shaded image. Fast 3DFT pulse sequences were optimized to enhance the time-of-flight contrast of the intravascular region. By increasing the surface threshold value in a three-dimensional head study, the flesh of a patient's face was peeled away to demonstrate the superfacial temporal artery. Gated cardiac images show the great vessels and cardiac chambers. A three dimensional view of the aorta shows an irregular surface in the vicinity of an adrenal tumor. 3D MR exams provide a non-invasive technique for assessing vascular morphology in a clinical setting. PMID- 2918819 TI - Post-pneumonectomy evaluation of the chest: a prospective comparative study of MRI with CT. AB - A comparative study of 11 pneumonectomized patients was undertaken in order to evaluate the respective advantages and drawbacks of MRI and CT in post-operative follow-up. Nine patients were healthy at the time of the study and two presented with tumor recurrence. MR examination included 500/40 ms axial, and frontal 800/40-80 ms or 1300/60-120 ms nongated spin echo sequences. MRI was slightly more efficient in identifying vascular stump and main nodal stations, and detected better than CT tumoral and metastatic spread in cancer recurrences. It was as informative as CT in evaluating postpneumonectomy space and bronchial stump. It was noncontributory in the detection of calcifications. Although clips were visible with MRI, their location was less definite than with CT, a potential pitfall when radiotherapy is planned. PMID- 2918820 TI - Intensity dependence of flow signal in slice selective velocity measurements. AB - The quantitative determination of flow velocities using inflow-outflow techniques require slice selective excitation pulses. The intensity-velocity relationship for such methods is shown to be such that flow velocities estimated using techniques which rely on an absolute calibration of the measured intensity are sensitive to the details of the slice profile of the excited material. This can cause errors when the estimation of flow velocities is made from the image intensity. A method which provides a measure of the flow velocities and which relies only on relative variations in intensity is examined and shown to be insensitive to details of the slice profile. PMID- 2918821 TI - MR imaging of model fluid velocity profiles. AB - A projection MR technique for imaging the velocity profiles of moving fluids has been applied to various steady flow models designed to simulate a variety of flow conditions. From such profiles can be readily deduced peak velocities, volume flow rates, information concerning the degree of flow development, features such as flow separation, and estimates shear stresses at the vessel wall. PMID- 2918822 TI - In vivo detection of applied electric currents by magnetic resonance imaging. AB - Magnetic resonance imaging is very sensitive to magnetic field variations. This inherent sensitivity can be exploited to measure small electric currents flowing in the human body. This report describes an experiment in which the magnetic fields produced by small currents applied to the forearm of a living subject have been detected in the tissue. It shows how such measurements have been used to measure current density. The suggested technique is used to measure one component of a current density in a saline solution in vitro. PMID- 2918823 TI - Assessment of T1 time course changes and tissue-blood ratios after Gd-DTPA administration in brain tumors. AB - Sequential T1 changes in brain tumor tissue after Gd-DTPA administration were investigated in 10 patients, including 4 meningiomas, 2 gliomas, 3 metastatic cerebral tumors and 1 brain abscess. T1 values were measured serially for 60 minutes following Gd-DTPA injection using a magnetic focusing technique. In vitro T1 of the whole blood samples was also comparatively examined. Time processes in the tissue-blood ratio (TBR) were calculated from two-point relaxation rates at 5 and 30 minutes. The obtained ratios of TBR were ranged from 1.0 to 3.0, probably depending on histological types of brain tumor (the value of 1.0 to 1.5 for meningioma and 1.5 to 3.0 for glioma and metastatic tumor). No significant changes in the T1 value were observed in the examined normal tissue and peritumoral edema. These results indicate that Gd-DTPA plays an important role not only as an image enhancer for tumor tissue but also as an indicator for estimating the blood-brain barrier function. PMID- 2918824 TI - Magnetic resonance imaging of the penis: normal anatomy. AB - This study was undertaken to investigate the magnetic resonance anatomy of the normal penis, by means of the use of a new designed surface coil specific for the study of male external genital organs. The combined evaluation of T1- and T2 weighted images obtained by choosing different repetition and echo time values together with an appropriate selection of scanning planes oriented according to various angles of incidence strongly contributed to perform a complete morphological analysis of the penis and constantly revealed fine anatomical details of diagnostic and clinical significance. Among these, the magnetic resonance examination (data referred to a 0.5 T apparatus) allowed a precise morphological differentiation of the penile covering tissues, such as outer skin, dartos tunica and hypodermal connective; the vascular characterization of cavernous tissue, belonging to corpora cavernosa and spongiosum urethrae, of deep arteries and superficial dorsal vein(s); the resolution of the albuginea and the identification of the urethral lumen. Such a capability of magnetic resonance imaging in providing accurate demonstration of penile structures without technical artifacts and use of ionizing radiations makes the actual technology able to cooperate efficaciously with computerized tomography and diagnostic sonography for an efficient clinical assessment of penis diseases. PMID- 2918825 TI - [A method for data processing in radionuclide angiography of the kidneys in nephroptosis based on anatomical zones]. PMID- 2918826 TI - [The microcirculation of the myocardium based on scintigraphic data using labelled microspheres]. AB - The authors described an original procedure for the determination of the organ blood flow with the help of 99mTc-labeled microspheres of aggregated albumin. Some features of the myocardial microcirculation in patients with CHD and without it were determined as well as interrelationships between the major coronary blood flow and the state of the myocardial microcirculation in various groups of CHD patients. A group of 32 males was examined. After thorough clinico-instrumental investigation CHD was diagnosed in 18 of them, 14 persons were taken as controls. Intraventricular administration of labeled microspheres during coronary angiography was followed by multipositional scintigraphy of the myocardium with further computer processing of images. A high sensitivity and specificity of the method was shown. The data obtained were compared with the results of other methods, among them those used by foreign researchers. PMID- 2918827 TI - [Kinetic study of human tissue metabolism of sodium using 22Na]. PMID- 2918828 TI - [X-ray fluorescent determination of iron, copper, zinc, bromine and rubidium in biopsies of the gastric mucosa]. AB - A method of a combined use of fiber gastroscopy and x-ray fluorescent analysis was elaborated for a study of the chemical composition of the gastric mucosa. Fr, Cu, Zn, Br, and Rb concentrations were determined in gastric mucosa biopsy specimens obtained during fiber gastroscopy, using x-ray fluorescent analysis. The concentrations of trace elements in the gastric mucosa were determined in 13 healthy persons, in 23 patients with chronic mucosal atrophy, in 15--with gastric ulcer, and in 16--with polyps. Besides, the content of trace elements was determined in the tumorous tissue of 66 gastric cancer patients. The results of the investigation revealed a statistically significant rise of mean Fr concentrations on the ulcer edge, in polyps and tumorous tissue as compared to the unchanged mucosa. Polypous tissue differed from the normal gastric mucosa by a low level of Cu, the difference being statistically significant. A tendency to a decrease in Zn content as compared to the unchanged mucosa was noted in the edge of ulcerative defects. The method can be effectively used for intravital studies on Fr, Cu, Zn, Br, and Rb levels in the G. I. tract mucosa. PMID- 2918829 TI - [Thermoradiotherapy of the late stages of cancer of the oral mucosa and oropharynx]. AB - Local UHF-hyperthermia (915 MHz) of cancer of the oral mucosa at advanced stages ensures higher immediate cure rates (48.9 +/- 7.5%) as compared to radiotherapy (26.8 +/- 6.9%). 30-min. hyperthermia before irradiation turned out more effective than 60-min. hyperthermia. Hyperthermia was attended by side-effects (fatigue and sweating, vertigo and pain in the zone of heating). Hyperthermia was not tolerated by 10.7% of patients. Fixed metal prostheses and crowns in the zone of planned hyperthermia should be removed. PMID- 2918830 TI - [Hemostasis in cancer patients during radiation therapy using metronidazole]. AB - Indices of platelet function, plasmic coagulation and fibrinolysis were studied during gamma-beam therapy in patients with laryngeal, gastric and cervical tumors (potentially at risk for thrombosis) against a background of metronidazole administration. During the above therapy the thrombophilic status of gastric cancer patients was preserved. These patients were considered at risk for thrombosis. In patients with laryngeal and cervical cancer platelet capacity to adhesion was considerably reduced during radiotherapy with the use of metronidazole. As a result of it the thrombogenic blood potential and danger of intravascular thrombogenesis were decreased. PMID- 2918831 TI - [Comparative evaluation of the results of combined radiation therapy in patients with primary vaginal cancer]. PMID- 2918832 TI - [The results of combined radiation therapy of stage-IB cervical cancer depending on the method of intracavity gamma therapy]. AB - The authors described the results of combined radiotherapy of 219 cervical cancer patients, stage TIBN0M0, of them 47 were treated by routine intracavitary gamma beam therapy including intracavitary irradiation based on the principle of successive administration of low activity radionuclide sources and 134 patients by that of high activity radionuclide sources. Gamma-beam therapy was of one type. There was no significant difference in 5-year survival rates in patients treated by combined radiotherapy including intracavitary gamma-beam therapy based on the principle of successive administration of low or high activity radionuclides. However, the survival rate in them as compared to that in patients treated by intracavitary irradiation of common type, was much higher. Rectal complications were most frequent in patients treated by routine radiotherapy, bladder complications were noted in patients treated by successive administration of high activity radionuclide sources. PMID- 2918833 TI - [Polyradiomodification. Optimization of the combined use of hyperglycemia and local hyperthermia in tumor irradiation]. AB - Therapeutic potentialities of various types of polyradiomodification were compared in experiments on mice with solid Ehrlich carcinoma by using separate and combined use of short-term hyperglycemia (SH) and local hyperthermia (HT). In the combination of modifiers SH was always created 3 h after the beginning of glucose administration. Irradiation of tumors was performed in either of 5 moments: 4 h or immediately before SH, in-between SH and HT, 30 min. or 2.5 h after SH. Two control schemes, in which irradiation was combined with one of the modifiers only, corresponded to each polyradiomodification regimen. The combined use of SH and HT produced a more noticeable effect than their separate action. A maximum effect on a tumor was observed in the combined use of both modalities shortly after irradiation, and it was not accompanied by enhanced skin radiation injury in a tumor growth zone. Irradiation after or in-between SH and TH resulted in enhanced skin radiation reactions. Thus, the highest therapeutic effect was noted in those schemes of polyradiomodification in which SH and HT followed radiation treatment. SH and HT induced suppression of the blood supply in tumors played an important role in the optimization of the combined use of SH and HT with irradiation. PMID- 2918834 TI - [Influence of the dose rate and postradiation hyperthermia on the cytogenetic effect of irradiation of cells in the G0 stage by 252Cf and 60Co sources]. AB - The paper is concerned with the results of a comparative study of radiation injury of chromosomes of human lymphocytes at the G0 stage resulting from the influence of 60Co gamma quanta and high activity 252Cf radiation sources and depending on a dose and dose rate; with the potentialities of modifying a cytogenetic effect of irradiation by postradiation hyperthermia of cells. It has been shown that at the G0 stage of a cell cycle the frequency of chromosome aberrations does not depend on the dose rate of 252Cf radiation within the range of 0.0035-0.35 Gy/min. by the neutron component. Linear correlation between the frequency of induced chromosome aberrations and a dose was observed within a dose range of 0.27-3.1 Gy. Thus, a conclusion is that postradiation hyperthermia at the G0 stage does not almost influence the frequency of chromosome aberrations during 252Cf radiation, and increases it insignificantly during 60Co gamma radiation. PMID- 2918835 TI - [The action of radiation on the differentiation process of myogenic cells in culture]. PMID- 2918836 TI - [199Tl chloride in the experimental assessment of myocardial perfusion. 2]. AB - Pharmacokinetic and scintigraphic studies on 199Tl were conducted. Pharmacokinetic characteristics of 199Tl chloride give an opportunity to use it for perfusion scintigraphy of the myocardium which is no inferior in the resolving power to 201T1. The shorter half-life of 199Tl will make it possible to reduce radiation exposure of an examinee. PMID- 2918837 TI - [Calculation of the parameters for teleradiotherapy procedures on the Iskra-226 computer]. AB - The mentioned computes calculates parameters for treatment sessions of the following types of gamma teletherapy: multizonal rotation irradiation with open fields, multizonal static irradiation with open fields and with the use of protective units in case of using AGAT and ROKUS-M apparatus. The employment of computer programs makes it possible to cut down (on the average from 20 to 2 min) the time consumed for calculation of parameters of irradiation for each patient, to avoid casual errors made in calculations by hand and to simplify drawing up of documents. PMID- 2918838 TI - [Potentials and outlook for radiation therapy of cancer patients on an outpatient basis]. AB - The paper is devoted to the problems of the organization of radiotherapy in an outpatient setting. Irradiation outside a hospital was demonstrated on 2500 patients with different primary and metastatic tumor lesions by way of an example. Social and economic advantages of this type of care were shown. PMID- 2918840 TI - Glucose intolerance, hyperinsulinemia and insulin resistance in aplastic anemia. AB - Oral glucose tolerance tests were conducted in 29 patients with aplastic anemia and 20 nondiabetic controls. Seventeen were men and 12 were women, ranging in age from 15 to 67 years. Based on the results of oral glucose tolerance test, the patients were divided into three groups: 14 previously treated cases with normal glucose tolerance; eight previously treated cases with abnormal glucose tolerance, of whom six had diabetes and two had impaired glucose tolerance; and seven newly diagnosed cases with normal glucose tolerance. Hyperinsulinemia and insulin resistance were observed in all patients. Multivariate analyses show that sex, age, body mass index, previous androgen and corticosteroid therapy, previous blood transfusion, initial hemoglobin and white blood cell and serum ferritin concentrations were not significantly related to hyperinsulinemia as expressed by the integrated insulin area under the curve of glucose tolerance test. Patients in the second group who had abnormal glucose tolerance had a delay in insulin secretion in response to glucose, indicating a deterioration of insulin reserve in the beta cells. Patients in this group were significantly older at the time of diagnosis than those in the first group. No other determinants of the development of abnormal glucose tolerance were demonstrated. PMID- 2918839 TI - Hormonally active long-term culture of human ovarian cells: initial characterization. AB - At present, to our knowledge, there are no long-term hormonally active cultures of normal human stromal ovarian cells. This report describes a method of developing such a system. Normal human stromal ovarian cells from three patients were cultured in McCoy's 5A tissue culture medium at 37 degrees C, 5% CO2, 95% humidity. The cells rapidly acquired fibroblastic appearance and grew in monolayers. The cells were trypsinized and passaged weekly. Tissue culture medium was collected and assayed for progesterone. The cells were initially producing 33.2 +/- 2.64 ng/mg protein of progesterone. By the eighth to twelfth passage, however, progesterone was no longer detectable in the medium. When the cells of the 12th passage were incubated with cholesterol, progesterone production resumed (8.9 +/- 0.09 ng/mg protein). When pregnenolone was used as a substrate, progesterone production was also present (8.06 +/- 0.24 ng/mg protein). Moreover, in the cells incubated with pregnenolone, progesterone production could be stimulated by adding 50 ng/mL FSH, or 50 ng/mL insulin to the incubation medium. Progesterone content of the medium increased to 11.3 +/- 0.29 ng/mg protein and 10.97 +/- 0.54 ng/mg protein respectively (P less than .05). The cells were also able to convert androstenedione to estrone. When the cells were incubated with 3 mumol/L androstenedione, estrone content of the medium ranged from 318 +/- 13 to 382 +/- 14 pg/mg protein. This finding suggests that aromatase is present in cultured human ovarian cells. These cells have now been maintained for 12 passages. A hormonally active long-term culture of normal human ovarian cells could be a useful tool in studies of ovarian physiology. PMID- 2918841 TI - Rate of weight loss during underfeeding: relation to level of physical activity. AB - The kinetics and bioenergetic-metabolic determinants of weight loss were examined in obese women ingesting 900 kcal/d for 5 weeks. The patients were assigned either to a sedentary group (n = 5) or to an exercise group (n = 6) in which the participants expended an additional (X +/- SD) 346 +/- 61 kcal/d in aerobic physical activity. The percentage weight loss and the fractional rates (K1 = fast component; K2 = slow component) of weight loss were almost identical between the two groups. The failure of added exercise to increase the velocity of weight loss could not be explained by differences between the groups in any of the following: gastrointestinal energy and nitrogen (N) absorption; fractional rates of urinary urea N and total N loss; or the thermic effect of the formula diet. The cumulative and fractional rates of protein (ie N) loss were also similar between the groups. The exercise group lost more fat (5.3 +/- 1.0 kg) than the non exercise group (4.4 +/- 1.6 kg, P less than .001) as measured by underwater weighing. The maximum between-group difference in the rate of fat loss, as determined by energy-N balance, occurred during early underfeeding. With continuation of the 900 kcal/d diet, the between-group differences in the rate of fat loss diminished. The exercise subjects significantly lowered their resting heat losses relative to the non-exercise subjects (P less than .025). This in turn reduced the degree of negative energy balance in the more energy-deficient exercise group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918842 TI - Appearance of multidisperse low density lipoprotein and altered lipoprotein composition in non-insulin-dependent diabetes with type IIa hyperlipoproteinemia. AB - The purpose of the present study is to elucidate the characteristics of lipoprotein disorders in diabetes mellitus. By analytical ultracentrifugation, non-insulin-dependent diabetic patients (NIDDM) with type IIa hyperlipoproteinemia (HLP) showed significantly higher incidence of multidisperse low density lipoprotein (LDL) than non-diabetics with type IIa HLP. Furthermore, LDL multidispersity in diabetic subjects seemed to be directly related to neither triglyceride (TG) levels in very low density lipoprotein (VLDL) nor the degree of glycemic control. Diabetics with multidisperse LDL had a lipoprotein profile that was different from the subjects with paucidisperse LDL as follows: (1) enrichment in the cholesterol content of VLDL, (2) TG-rich LDL with small flotation coefficient, (3) low cholesterol levels in high density lipoprotein2 along with enrichment in TG, and (4) high plasma concentrations of apoprotein B. Although the underlying mechanism behind the prevalence of multidisperse LDL in NIDDM with type IIa HLP remains unknown, it seems important that lipoprotein disorders in diabetics with multidisperse LDL were potentially atherogenic. PMID- 2918843 TI - Rat hepatic and renal 5'-deiodination of rT3 during fasting: supportive role of intermediate Mr cytosolic non-glutathione thiol cofactor and NADPH. AB - The roles of subcellular components and, in particular, cytosol fractions and beta-nicotinamide adenine dinucleotide phosphate, reduced form (NADPH), in the regulation of rat hepatic and renal 5'-deiodination during fasting were assessed. 5'-deiodinase (5'-DI) activities in reaction mixtures were measured by using outer ring 125I-radiolabelled reverse triiodothyronine (rT3) as a substrate in the presence of 200 mumol/L NADPH. Subcellular components from rats fed ad libitum or fasted for 24, 48 or 72 hours were prepared by standard differential centrifugation. Cytosol was chromatographed on a Sephadex G-50 column to obtain Fraction A of molecular weight (Mr) greater than 60,000 and Fraction B of Mr approximately 13,000 and to exclude reduced glutathione (GSH) (Mr less than 400). 5'-DI activity in liver homogenates was reduced by 42% at 24 hours and by 59% at 48 hours of fasting. In reconstitution experiments, liver microsomes showed a progressive loss of 5'-DI activity, reaching a maximal reduction of 46% at 72 hours of fasting. Activation of microsomal deiodinase by whole liver cytosol was also significantly reduced at 24 hours of fasting and achieved a maximal reduction of 5'-DI activation of 42% at 48 hours before substantial but incomplete recovery at 72 hours. Cytosolic Fraction A and B were assessed in combination with fed microsomes and NADPH. A close correlation was demonstrated between the loss of hepatic 5'-DI supportive activity in whole cytosol and that of Fraction B but not A during fasting.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918844 TI - Plasma histamine concentrations are elevated in patients with diabetes mellitus and peripheral vascular disease. AB - Previous work has shown that plasma and tissue concentrations of histamine are elevated in rats with experimental diabetes mellitus and that leucocytes and platelets from patients with peripheral vascular disease have a higher histamine content than those from controls. In the present study, we have measured: (a) plasma histamine concentrations; (b) leucocyte and platelet histidine decarboxylase (the enzyme responsible for the biosynthesis of histamine) in patients with diabetes mellitus (Types I and II) and peripheral vascular disease; and (c) platelet and leucocyte histamine content. Plasma histamine concentration was significantly higher in patients with diabetes and peripheral vascular disease respectively than that in age-matched controls. Leucocyte histidine decarboxylase activity in diabetic and peripheral vascular disease patients was similar to that in controls, while platelets had no histidine decarboxylase activity. The leucocyte and platelet content of histamine were greater in patients with peripheral vascular disease than those in controls, but they were not altered in diabetic patients. There was no correlation between plasma histamine concentration, leucocyte and platelet histamine content, and histidine decarboxylase activity. We conclude that plasma histamine is elevated in diabetics and in patients with peripheral vascular disease and that platelet and leucocyte histamine content is increased in the latter. This increase in platelet and leucocyte histamine content is not due to an increase in histidine decarboxylase activity of these cells. The increase in plasma and cellular histamine content may contribute to the pathogenesis of increased endothelial permeability in diabetes and to the pathogenesis of intimal damage in atherosclerosis. PMID- 2918845 TI - Regulation of low density lipoprotein apoprotein B metabolism by lovastatin and cholestyramine in miniature pigs: effects on LDL composition and synthesis of LDL subfractions. AB - A major factor in the regulation of low density lipoprotein (LDL) apoprotein B (apo B) concentrations in miniature pigs is the direct synthesis of LDL apo B. LDL apo B derived from plasma very low density lipoproteins (VLDL) accounts for only 20% to 30% of total LDL synthesis. Treatment with lovastatin and cholestyramine can inhibit the direct synthesis pathway in this species, thereby lowering LDL apo B concentrations. The present study was carried out to determine if lovastatin alone was as effective as in combination with cholestyramine. The possibility that the direct synthesis pathway was confined to a specific subclass of LDL and the effect of lovastatin and cholestyramine on the metabolism of LDL subfractions were also investigated. Homologous 125I-VLDL and 131I-LDL were injected into miniature pigs during a control period and again following 18 days of treatment with lovastatin (1.2 mg/kg/d, n = 4) or in combination with cholestyramine (1.0 g/kg/d, n = 4). Kinetic analysis of apo B specific activity curves following lovastatin treatment indicated that LDL apo B pool size was decreased by 25% (P less than .025), which was due entirely to a 70% (P less than .025) decrease in the direct synthesis of LDL apo B, since VLDL-derived apo B, and LDL fractional catabolic rate (FCR) were not affected. Parameters of VLDL apo B metabolism were not affected. Lovastatin in combination with cholestyramine was more effective than lovastatin alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918846 TI - Low-dose colestipol plus fenofibrate: effects on plasma lipoproteins, lecithin:cholesterol acyltransferase, and postheparin lipases in familial hypercholesterolemia. AB - Effects on plasma lipoproteins, lecithin:cholesterol acyltransferase (LCAT), and postheparin lipase (LPL and HTGL) activities were studied in 18 patients with familial hypercholesterolemia during 8-week treatment periods with colestipol (15 g/d), fenofibrate (0.25 g/d), and colestipol plus fenofibrate. Lipoprotein lipids and apolipoproteins were determined by standard procedures, LCAT by a self substrate method, and lipases by nonradioisotopic methods. Colestipol and fenofibrate, each given independently, caused similar percentage decreases in LDL cholesterol and apolipoprotein B: -18.4% and -8.6% v -17.4% and -10.6% Colestipol increased the VLDL cholesterol concentration, whereas fenofibrate reduced this parameter but increased HDL cholesterol and apolipoprotein A-I levels. The combination of both drugs led to a substantial fall in LDL cholesterol (-36.8%) and in apolipoprotein B (-28.3%) and maintained the other effects of fenofibrate on VLDL and HDL. Colestipol, given independently or with fenofibrate, produced an increase of the fractional esterification rate of the LCAT enzyme (+25.3% and +36.2%). Fenofibrate stimulated the postheparin LPL enzyme by +16.1% and +21.7%, respectively. This study indicates the complementarity in effectiveness when both drugs were administered together. The appropriate reduction in LDL was combined with the favorable effects on HDL in familial hypercholesterolemia. PMID- 2918847 TI - Glucose-alanine relationship in normal human pregnancy. PMID- 2918848 TI - Formula diets for obesity. PMID- 2918849 TI - [Clinical and laboratory chemical studies of the incidence and extent of diabetic cheiropathy in childhood and adolescence]. AB - Diabetic cheiropathy is often not diagnosed because of a paucity of symptoms. In the present study, 100 type I diabetic patients and 20 controls were investigated. The age of patients ranged from seven to 26 years, the duration of diabetes was one to 23 years. Extension of hands by "prayer position", a hand print and angle determinations of joints were considered for the determination of diabetic cheiropathy. The presence of cheiropathy was unrelated to the duration of diabetes. However, it was well correlated with the quality of blood sugar control and it was often associated with diabetic retinopathy: Diabetic cheiropathy was detected in 53 (53%) of the diabetic patients, and in 26 (49%) of them diabetic retinopathy was also diagnosed. Only three patients had a retinopathy without cheiropathy. On the basis of our results, diabetic cheiropathy is a surprisingly common feature in young type I-diabetics. It is not to be considered as a late complication but rather a sequel of badly controlled diabetes mellitus. PMID- 2918850 TI - [Description and assessment of a rapid new method for measuring erythrocyte sedimentation rate]. AB - A new method for the rapid photometric determination of the erythrocyte sedimentation rate (ESR) is described and compared with the Westergren technique. The basis of this method is the development of a new physical equation valid for transport processes, in which sedimentation processes can be described by means of a linear regression analysis. After the mathematical transformation, the measured ESR data follow a linear function. The apparatus evaluated measures within a few minutes the velocity profile of the ESR over a distance of about 2 X 10(-4) meter by kinetic determination of the optical density of a short blood column filled in a small cuvette. A microprocessor calculates the linear regression and derives the one and two hour values by extrapolation. The correlation of this method with the standard Westergren technique, determined over 20 days is acceptable (R = 0.95; n = 368). The reproducibility of the same sample (n = 20) is better than that of the conventional procedure. The reproducibility determined with different instruments (n = 20) is comparable to the precision of the Westergren method. The practical value of this new time- and blood-saving, well standardized method for an efficient patient-care is discussed. PMID- 2918851 TI - [Differential diagnosis and therapy of cycle-dependent severe attacks of familial Mediterranean fever]. PMID- 2918852 TI - [Is asthma a psychosomatic disease?]. PMID- 2918853 TI - [Antibodies, clinical and hematologic findings in immunoneutropenias]. AB - Sera were analyzed from patients who were suspected to have antibodies to neutrophils. The analysis comprised five methods which avoid heterologous antibodies to human immunoglobulin. These methods were the granulocyte agglutination test (GAT), the granulocyte cytotoxicity test (GCT), the monocyte cytotoxicity test (MCT), the lymphocyte cytotoxicity test (LCT) and immune phagocytosis inhibition test (IPI). Each serum was tested with cells from five healthy donors, at least, and some with cells from relatives. After exclusion of sera containing multiple antibodies and HLA-antibodies with positive LCT- and IPI tests, the GAT- or GCT-reactive antibodies were significantly (p = 0.00005) more frequent among patients with neutrophil counts less than or equal to 1.0 X 10(9)/l (30%; n = 117) than among patients with neutrophil counts greater than 1.0 X 10(9)/l (9%; n = 111). Within the group of neutropenic patients (less than or equal to 1.0 X 10(9)/l) these antibodies were significantly (p = 0.001) more frequent in patients without (48%; n = 46) than with reduction of the granulopoiesis (13%; n = 31). This typical feature of an immune cytopenia also could be shown with GAT-reactive antibodies alone. From all five antibody tests the diagnostic criteria of the autoimmune neutropenia (AINP) and neonatal alloimmune neutropenia (NIN) were infered. 25 patients with clearly defined AINP presented with significantly more infectious complication than 23 patients with only assumed AINP (48% versus 13%). Further, the clinical findings of eight patients with NIN were described. --Antibodies only reactive in the GAT were detected in healthy individuals (1.3%; n = 75) and patients without indication for AINP or NIN (8%; n = 111), also.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918854 TI - Gallamine exerts biphasic allosteric effects at muscarinic receptors. AB - Although gallamine and a number of other compounds have been reported to slow the rate of dissociation of labeled ligands, especially [3H]N-methylscopolamine (NMS), from muscarinic receptors of heart and brain, there has been some dispute as to whether the dissociation of [3H]quinuclidinyl benzilate (QNB) is subject to such allosteric regulation. The present studies were intended to determine whether past discrepancies might be due to differences between tissues. We have found that gallamine modulates the dissociation of [3H]QNB from muscarinic receptors of the heart in a biphasic manner. Low concentrations (micromolar) accelerate the rate of dissociation, whereas higher concentrations (millimolar) slow it; at about 0.1 mM, the two effects cancel each other. Similar results were obtained with muscarinic receptors from the brainstem, but gallamine had only marginal effects on the dissociation of [3H]QNB in the forebrain. On the other hand, verapamil exerts only monophasic effects (slowing) on the dissociation of both [3H]NMS and [3H]QNB from heart receptors and gallamine slows the dissociation of [3H]NMS to a similar extent in all three tissues. Thus, it appears that past discrepancies in the literature can be attributed to the tissues and concentrations of gallamine that were used. Furthermore, the biphasic effects of gallamine suggest that there are multiple allosteric regulatory sites associated with muscarinic receptors. PMID- 2918855 TI - Investigations into the biochemical effects of region-specific nephrotoxins. AB - 1H NMR spectroscopy provides a useful initial biochemical screen with which to detect abnormal patterns of metabolites in urine collected from animals with different sites of nephrotoxic lesions. Male Fischer 344 rats were treated with nephrotoxic doses of sodium chromate (pars convoluta of proximal tubule), cisplatin, hexachlorobutadiene, mercury II chloride (pars recta of proximal tubule), propylene imine, and bromoethanamine (renal papilla) in order to induce damage in specific regions of the kidney. Urine was collected for up to 48 hr after dosing and was analyzed by 1H NMR spectroscopy (400 MHz) and conventional biochemical methods to provide biochemical fingerprints of urine in various site specific nephrotoxic states. Hexachlorobutadiene and HgCl2 produced severe glycosuria and transient enzymuria. 1H NMR urinalysis revealed aminoaciduria, glycosuria, and lactic aciduria after exposure to all proximal tubular toxins except cisplatin, whereas papillary insult resulted in early elevations in urinary trimethylamine N-oxide and dimethylamine, together with later elevations in urinary acetate, succinate, and N,N-dimethylglycine (after propylene imine). Trimethylamine N-oxide and dimethylamine are suggested as novel markers of site specific renal papillary injury in the rat. PMID- 2918856 TI - Joint experimental and theoretical investigation of the comparative DNA binding affinities of intercalating anthracycline derivatives. AB - The comparative binding affinities for poly(dA-dT) and poly(dG-dC) of novel antitumor anthracyclines are reported. The data concern, besides the parent compound adriamycin (ADM), 4-demethoxy 6-deoxy 6-aminodaunomycin (II), 9-deoxy ADM (III), 4-demethyl-6-O-methyl-ADM (IV), and 3'-deamino-3'-hydroxy-4'-epi-ADM (IV). Theoretical computations are performed in parallel for their comparative binding affinities to model double-stranded hexanucleotides, d(GCGCGC)2, d(TATATA)2, and d(CGTACG)2, using the SIBFA (sum of interactions between fragments computed ab inito) procedure. The computations reproduce in a very satisfactory manner the most salient features of the experimental comparative binding affinities. These encompass, in particular, a higher affinity for the d(TATATA)2 oligomer of II than that of ADM, despite the absence of the 14-OH substituent in II, a marked reversal of the CG versus TA sequence selectivity of the neutral compound V, favoring the d(CGCGCG)2 oligomer over the d(TATATA)2 one; and the deleterious effect incurred on the binding affinities by the presence of an O-methyl substituent at position 6 of the chromophore. PMID- 2918857 TI - Oral immunization with a free peptide from cholera toxin: local protection and IgA production. AB - It is frequently of great benefit for good protection against pathogens to elicit a local immunization. For example the importance of antibacterial as well as antitoxin local secretory IgA, for protection against cholera, has been underlined in several studies. We have already reported that oral administration of the peptide corresponding to the 50-75 sequence of cholera toxin (CT) B subunit elicits serum antibodies neutralizing CT activity. In this study we demonstrate that IgA with specificity to CT are present in intestinal secretions of mice immunized orally with the P50-75 or P30-50 peptides of CT B subunit. In addition local protection is observed in the intestine of P50-75 orally immunized mice. These results point out the potential of synthetic peptides as immunogens at the mucosal level. PMID- 2918858 TI - Enhanced transmembrane signalling activity of monoclonal antibody heteroconjugates suggests molecular interactions between receptors on the T cell surface. AB - Signal transduction occurs through multiple receptors expressed on mature, resting T cells. In addition to the CD3-T cell receptor complex, the CD2, CD4, CD5, CD7, CD8 and CD28 receptors mobilize cytoplasmic calcium within minutes of binding with monoclonal antibodies and additional crosslinking occurs on the cell surface. As an approach to study the interactions between these receptors and their transduced signals, monoclonal antibodies to each of these receptors were covalently coupled as heteroconjugates and investigated for activity in cytoplasmic calcium mobilization using indo-1 and flow cytometry. Of a total of 35 conjugates studied, there were seven heteroconjugates that showed an increase in activity and these consisted of either certain conjugates of anti-CD3 or certain conjugates of anti-CD5. The CD3-CD2, CD3-CD4, CD3-CD6 and CD3-CD8 heteroconjugates each gained two to three orders of magnitude in titer in calcium mobilization compared to unconjugated CD3 or the CD3-CD3 conjugate. The increase in activity was not accompanied by an increase in binding titer, indicating that signal transduction occurred at lower levels of receptor occupancy. The increased activity was dependent in each case on the relevant second receptor, since unconjugated CD2, CD4, CD6 or CD8 MAb could block the activity of the corresponding heteroconjugate. Neither CD3-CD5, CD3-CD28 or CD3-CD3 conjugates gained activity, whereas CD3-CD7 heteroconjugates gained slightly in activity. The heteroconjugates with CD5 that acquired ability to mobilize calcium at low concns (less than 5 micrograms/ml) were CD5-CD4, CD5-CD8 and CD5-CD6. Their activity could be inhibited by either CD5 MAb or the second MAb of the heteroconjugate. The increased activity of CD3 or CD5 heteroconjugates was observed in the absence of extracellular calcium. Size exclusion chromatography of heteroconjugates demonstrated that 1:1 ratios were optimal, but larger conjugates were also active. These results suggest that certain receptors are capable for molecular interactions on the cell surface to form complexes with enhanced activity in signal transduction leading to calcium mobilization. PMID- 2918859 TI - Characterization of a broadly expressed human leucocyte surface antigen MEM-43 anchored in membrane through phosphatidylinositol. AB - A monoclonal antibody MEM-43 was prepared, which recognizes an antigen expressed on all peripheral blood leucocytes, on erythrocytes and several cell lines, but is absent from U937, Nalm-6, Daudi and Raji cell lines. The antigen isolated by immunoaffinity chromatography from several cell lines is an 18,000-25,000 mol. wt glycoprotein. An apparently identical antigen isolated from erythrocytes binds to several lectins and has a 14,000 mol. wt polypeptide backbone, modified by an endoglycosidase F-sensitive carbohydrate moiety. The epitope recognized is reduction-sensitive. The sequence of N-terminal 17 amino acid residues was determined; five out of six N-terminal amino acids are identical to those found at the N-terminus of the mouse lymphocyte surface antigen Ly-6C. The antigen is completely released from the cell surface after treatment with phosphatidylinositol-specific phospholipase C. PMID- 2918860 TI - Carbohydrate binding specificity of the basic lectin from winged bean (Psophocarpus tetragonolobus). AB - The carbohydrate binding specificity of the basic lectin from winged bean (Psophocarpus tetragonolobus) was investigated by quantitative precipitin analysis using blood group A, B, H, Le and I substances and by precipitation inhibition with various mono- and oligosaccharides. The lectin precipitated best with A1 substances and moderately with B and A2 substances, but not with H or Le substances. Inhibition assays of lectin-blood group A1 precipitation demonstration that A substance-derived oligosaccharides having the common structure: D-GalNAc alpha(1----3)D-Gal-(beta 1----3/4) to a D-Glc, were the best inhibitors and about 8 and 4 times more active than D-GalNAc and D-GalNAc alpha(1 ---3)D-Gal, respectively. A difucosyl A-specific oligosaccharide (A-penta), a monofucosyl (A-tetra) and a non-fucosyl containing (A5II) oligosaccharide, D GalNAc alpha(1----3)D-Gal beta(1----3)D-GlcNAc, had almost the same reactivity, suggesting that the fucose linked to the sub-terminal D-Gal or to the third sugar. D-GlcNAc, from the non-reducing end made no contribution to the carbohydrate binding. Although a terminal non-reducing D-GalNAc or D-Gal residue was indispensible for binding, the lectin bound not only to these terminal non reducing galactopyranosyl residues, but also showed increased binding to oligosaccharides in which it was bonded to a sub-terminal D-Gal joined to a D GlcNAc residue, as in blood group A or B substances. This defines the site, thus far, as complementary to a disaccharide plus the beta linkage to the third sugar (D-Glc or D-GlcNAc) from the non-reducing end. The role of the beta(1----3) or beta(1----4) linkage of the sub-terminal non-reducing D-Gal to the D-GlcNAc requires further study. PMID- 2918861 TI - Quantitative methods for assessing a synergistic or potentiated genotoxic response. AB - The problem of assessing chemical interactions in studies of genotoxicity is discussed. Attention is focused on assessing possible synergism or potentiation when the observed genotoxic response is binary (yes-no). Different forms of enhancement are distinguished based upon different assumptions on the genotoxic activity of the experimental treatments. A generalized linear statistical model is considered that links the probability of the binary response to the doses, and data-analytic strategies are described for detecting synergy and potentiation in factorially designed experiments. This approach is illustrated with a series of analyses of various genotoxicity data-sets. PMID- 2918862 TI - Generation of PM2 DNA breaks in the course of reduction of chromium(VI) by glutathione. AB - The carcinogen chromate is efficiently taken up and reduced to chromium(III) compounds by various biological systems. To test the possible DNA damage induced in the course of chromium(VI) reduction, we used a combination of chromate with the reductant glutathione (GSH) as well as a green complex of chromium(V), which is formed in the reaction of chromate with GSH. The combination of chromate and glutathione was found to cause single-strand breaks in supercoiled circular DNA of the bacteriophage PM2. The green chromium(V) complex Na4(GSH)4Cr(V).8H2O, prepared from chromate and glutathione, also cleaved supercoiled PM2 DNA. No DNA degrading effects were observed with either chromate or the final product of the reaction with GSH, a purple anionic chromium(III) GSH complex. The nature of the buffering agents revealed a strong influence on the extent of DNA strand breaks produced by chromate and GSH. A variation of the GSH concentration in the reaction with chromate and PM2 DNA, performed in sodium phosphate-buffered solutions showed an initial increase in the number of strand breaks at GSH concentrations up to 1 mM followed by a decline at higher GSH concentrations. Since neither chromate, when administered individually, nor the final product of chromium(VI) reduction, the purple chromium(III) GSH complex, produced any detectable DNA cleavage, the critical steps leading to DNA strand breaks occur in the course of the conversion of chromium(VI) to chromium(III) by GSH, the most abundant intracellular low molecular thiol. Moreover, the demonstration that DNA cleavage is induced in the presence of the chromium(V) complex identifies chromium(V) as the oxidation state of the metal, which is involved in the steps leading to DNA-damaging effects of chromate. PMID- 2918863 TI - Mutation at the hprt locus. Stockholm, May 26-28, 1988. Abstracts. PMID- 2918864 TI - A comparison of mutation induction at the tk and hprt loci in human lymphoblastoid cells; quantitative differences are due to an additional class of mutations at the autosomal tk locus. AB - X-Rays, ethyl methanesulfonate and ICR-191 induced 2 classes of trifluorothymidine-resistant mutants at the autosomal tk locus in human lymphoblastoid cells. These classes were differentiated by their growth rates; some mutants grew with a normal doubling time of 14-18 h (tk-NG), while others grew much more slowly, with doubling times of 21-44 h (tk-SG). Only mutants with normal growth rates were observed at the X-linked hprt locus; the frequencies of mutations induced at hprt were equal to those induced for tk-NG mutants. Thus, more mutations overall (by up to a factor of 6) were induced at tk than at hprt. These results are discussed in relation to recent studies in rodent cells, in which much greater mutation frequencies were observed at autosomal loci. PMID- 2918865 TI - Excision repair characteristics of denV-transformed xeroderma pigmentosum cells. AB - Introduction of the denV gene of phage T4, encoding the pyrimidine dimer-specific endonuclease V, into xeroderma pigmentosum cells XP12RO(M1) was reported to result in partial restoration of colony-forming ability and excision repair synthesis. We have further characterized 3 denV-transformed XP clones in terms of rates of excision of pyrimidine dimers and size of the resulting resynthesized regions following exposure to 100 J/m2 from an FS-40 sunlamp. In the denV transformed XP cells we observed 50% dimer removal within 3-6 h after UV exposure as compared to no measurable removal in the XP12RO(M1) line and 50% dimer excision after 18 h in the GM637A human, control cells. Dimer removal was assayed with Micrococcus luteus UV-endonuclease in conjunction with sedimentation of treated DNA in alkaline sucrose gradients. The size of the resulting repaired regions was determined by the bromouracil photolysis technique. Based on the photolytic sensitivity of DNA repaired in the presence of bromodeoxyuridine, we calculated that the excision of a dimer in the GM637A cells appears to be accompanied by the resynthesis of a region approximately 95 nucleotides in length. Conversely, the resynthesized regions in the denV-transformed clones were considerably smaller and were estimated to be between 13 and 18 nucleotides in length. These results may indicate that either the endonuclease that initiated dimer repair dictated the size of the resynthesized region or that the long-patch repair observed in the normal cells resulted from the repair of non-dimer DNA lesions. PMID- 2918866 TI - Microinjection of T4 endonuclease V produced by a synthetic denV gene stimulates unscheduled DNA synthesis in both xeroderma pigmentosum and normal cells. AB - A structural gene for T4 endonuclease V was constructed by ligating synthetic oligonucleotides. The endonuclease V was overproduced in E. coli under control of the E. coli tryptophan promoter and purified to apparent homogeneity. The product had comparable DNA glycosylase and apurinic/apyrimidinic (AP) endonuclease activities to the natural enzyme in vitro. When this endonuclease V was microinjected into the cytoplasm of xeroderma pigmentosum (XP) cells of complementation group A, B, C, D, F, G or H, unscheduled DNA synthesis (UDS) above the residual level was detected in all the cells at a dose of about 10(3) molecules following UV irradiation. The gain numbers of UDS in these XP cells increased with increase in the dose of enzyme and reached a plateau at the normal cell level on introduction of about 10(4) molecules. Introduction of more enzyme into either XP cells or normal human cells did not increase the grain number under regular labelling conditions (2.5 h, 37 degrees C). In normal mouse cells, introduction of the enzyme increased the grain number more than 4-fold under the same conditions during at least 8.5 h following UV irradiation. Furthermore, with a labelling time of 30 min, the enzyme more than doubled the grain number even in normal human cells. PMID- 2918867 TI - DNA methylation in xeroderma pigmentosum. AB - DNA methylation was examined in xeroderma pigmentosum (XP) cells. The amount of 5 methylcytosine (mC) in DNA from XP cells was about 70% of that in DNA from normal controls. Southern hybridization analysis showed that the HLA-DR alpha gene in XP lymphocyte B cells was differently methylated from normals, but its expression was apparently unaffected. The methylation of dihydrofolate reductase, a housekeeping gene, was the same as in controls. The revertants to UV resistance from XP fibroblasts recovered a methylation level close to that of normal cells. Results suggested that XP DNA was undermethylated non-randomly, and that DNA methylation might be associated with DNA repair function. PMID- 2918868 TI - Homologous recombination is not enhanced in UV-irradiated normal and repair deficient human fibroblasts. AB - Many mammalian cells exhibit damage-inducible phenomena that resemble the bacterial SOS functions. However, whereas RecA plays a prominent role in the prokaryotic SOS response, in mammalian cells so far no enhanced recombination as a result of treatment with DNA-damaging agents of the cells, rather than of infecting viruses, has been found. In order to study recombination as a UV inducible cellular phenomenon we infected UV-irradiated normal and repair deficient human fibroblasts with a mixed population of adenovirus 5 (Ad5) mutants that carried a deletion in the E1A or the E2A gene. Wild-type recombinant progeny viruses were readily obtained, but no enhanced recombination was observed at any UV dose given to the cells, nor at any time point between -6 h and +4 days between irradiation and infection. Control experiments, in which we infected unirradiated cells with UV-irradiated Ad5 deletion mutants (a test for recombination targeted at UV-damaged DNA) showed a strong increase in wild-type recombinant viruses when both deletion mutants had been irradiated compared to the additive effect of irradiation of either one of the mutants alone. Therefore, this study shows that UV irradiation results in an enhanced recombination activity in cells that is specifically targeted to damaged DNA, but it does not cause a general (untargeted) recombinational response (enhanced recombination) in the cell. PMID- 2918869 TI - The cloned human DNA excision repair gene ERCC-1 fails to correct xeroderma pigmentosum complementation groups A through I. AB - The human DNA excision repair gene ERCC-1 complements the ultraviolet light (UV) and mitomycin C (MMC) sensitivity of CHO mutants of complementation group 1. We have investigated whether ERCC-1 is the mutated gene in cell lines from xeroderma pigmentosum (XP) complementation groups A through I by analyzing the endogenous gene in XP cells and by introduction of the gene followed by repair assays. Our studies show that ERCC-1 is not deleted or grossly rearranged in representative cell lines of 9 XP groups. Furthermore, Northern blot analysis revealed correct transcription of ERCC-1 in all groups. The cloned human ERCC-1 gene was introduced into immortalized XP cells by DNA transfection (groups A, C, D, E and F). The presence of the integrated transfected sequences was verified on Southern blots and by selection for 2 dominant marker genes that flank the ERCC-1 gene on the transfected cos43-34 DNA. ERCC-1 failed to confer a normal UV survival and UV induced unscheduled DNA synthesis (UDS) to transfected populations. In the case of the remaining XP complementation groups (B, G, H and I), nuclear microinjection was used to introduce an ERCC-1 cDNA construct driven by an SV40 promoter into primary fibroblasts. Coinjection of the SV40 large T gene and analysis of its expression served as a control for the injection. The ERCC-1 cDNA failed to induce increased levels of UDS in the microinjected fibroblasts. We infer from these experiments that ERCC-1 is not the mutated gene in the 9 XP complementation groups examined. From a similar type of experiments we conclude that ERCC-1 is not the defective gene in UV-sensitive Cockayne's syndrome cells. PMID- 2918870 TI - Cytogenetic effects of tobacco smoke exposure among involuntary smokers. AB - Tobacco smoke is highly genotoxic and produces chromosomal damage in several experimental systems. Active smokers have been shown to have an increased prevalence of somatic chromosome damage in their peripheral blood lymphocytes: this is seen in most cases as an increased sister-chromatid exchange (SCE) frequency and often also as increased structural chromosome aberrations (CAs). Among passive smokers, in association with exposure to environmental tobacco smoke, no such induction of chromosomal damage has been documented. In the present paper we report negative results on induction of chromosomal damage in 2 separate groups of intensive involuntary exposure to tobacco smoke, non-smoking restaurant personnel and newborn children of smoking mothers. While significant exposure in these groups is clearly seen in biochemical intake markers, e.g. cotinine and thiocyanate values in plasma, the conventional cytogenetic parameters, structural chromosome aberrations and sister-chromatid exchanges, are unable to detect the low exposures of involuntary smokers. PMID- 2918871 TI - Passive smoking and lung cancer: current evidence and ongoing studies at the International Agency for Research on Cancer. AB - The evidence available from 3 cohort and 11 case-control studies investigating the relationship between exposure to environmental tobacco smoke (ETS) and lung cancer in non-smokers is reviewed. While it appears most likely that a causal relationship exists, the size of the effect, under different circumstances of exposures, remains to be accurately estimated. This requires studies using valid instruments (e.g., questionnaires) to quantitate exposures, and free as far as possible from biases. An investigation addressing this point is in progress under the coordination of the International Agency for Research on Cancer. PMID- 2918872 TI - Population burden of lung cancer due to environmental tobacco smoke. AB - The population burden of lung cancer due to environmental tobacco smoke is significant because a large fraction of the population is exposed. The risks are, of course, lower than those to smokers themselves; but smoking is self-inflicted, passive smoking is involuntary. Making various assumptions, the proportion of lung cancer cases among non-smokers that could reasonably be attributed to environmental tobacco smoke can be calculated to be about 20-30% in western countries. Thus, non-smokers in the society could benefit considerably from diminishing exposures to other people's smoke. PMID- 2918873 TI - Environmental tobacco smoke and passive smoking. Papers from a symposium. Helsinki, June 9-12, 1987. PMID- 2918874 TI - Prediction of relapse or survival in patients with node-negative breast cancer by DNA flow cytometry. AB - More accurate prediction of the prognosis in women with node-negative breast cancer may improve physicians' ability to identify the patients most likely to benefit from systematic adjuvant therapy. With this in mind, we performed DNA flow-cytometric measurements of ploidy and the fraction of cells in the synthesis phase of the cell cycle (S-phase fraction) on 395 specimens of node-negative breast cancer from our bank of frozen tumors, using the aliquots of pulverized frozen tissue from steroid-receptor assays. The median duration of follow-up in patients still alive at the time of analysis was 59 months. Thirty-two percent of the 345 specimens that could be evaluated were diploid, and 68 percent were aneuploid. The probability of disease-free survival at five years was 88 +/- 3 percent in patients with diploid tumors and 74 +/- 3 percent in those with aneuploid tumors (P = 0.02). The S-phase fraction was not a significant additional predictor of disease-free survival in patients with aneuploid tumors. However, the probability of disease-free survival in patients with diploid tumors and low S-phase fractions was 90 +/- 3 percent at five years, as compared with 70 +/- 13 percent in those with diploid tumors and high S-phase fractions (P = 0.007). Similar differences in overall survival were noted. We conclude that DNA flow-cytometric measurements of ploidy and S-phase fraction can be performed on frozen specimens of tumors and are potentially important predictors of disease free and overall survival in patients with node-negative breast cancer. PMID- 2918875 TI - Dissolution of cholesterol gallbladder stones by methyl tert-butyl ether administered by percutaneous transhepatic catheter. AB - We treated 75 patients with symptomatic cholesterol gallstones by dissolving the stones with methyl tert-butyl ether (MTBE) instilled into the gallbladder through a percutaneous transhepatic catheter. The MTBE was continuously infused and aspirated manually four to six times a minute, for an average of five hours per day for one to three days; the treatment was monitored by fluoroscopy. The placement of the catheter and the administration of MTBE caused few side effects or complications, and treatment did not have to be stopped in any patient for this reason. In 72 patients there was complete dissolution of stones or more than 95 percent dissolution. Among 21 patients who were completely free of stones after treatment, 4 had recurrence of stone formation 6 to 16 months later. The other 51 patients had residual debris, which spontaneously cleared completely in 15 patients within 6 to 35 months; only 7 with persisting debris have had symptoms. Five of the initial 6 patients treated, but only 1 of the next 69 patients, have required surgery during follow-up periods of 6 to 42 months. We conclude that the dissolution of gallstones by MTBE delivered through a percutaneous transhepatic catheter is a useful alternative to surgery in selected patients with symptomatic cholesterol stones. Further study will be necessary to establish the long-term effectiveness of this treatment and its appropriate role in the management of the various types of gallstones. PMID- 2918876 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 10-1989. A 60-year-old man with a large right atrial mass. PMID- 2918877 TI - Prenatal diagnosis--advances bring new challenges. PMID- 2918879 TI - Acute rhabdomyolysis associated with cocaine intoxication. PMID- 2918878 TI - Nonsurgical treatment of gallstones. PMID- 2918880 TI - Changes in lipoproteins during weight loss. PMID- 2918881 TI - Automatic external defibrillator for out-of-hospital cardiac arrest. PMID- 2918882 TI - Successful pregnancy in a previously infertile woman treated with SMS-201-995 for acromegaly. PMID- 2918883 TI - Hypoferremia: adaptation to disease? PMID- 2918884 TI - Alternative therapies used by patients with AIDS. PMID- 2918885 TI - Delayed death from ingestion of a toothpick. PMID- 2918887 TI - Fraud on the agenda. PMID- 2918886 TI - DNAR: do not attempt resuscitation. PMID- 2918888 TI - Ozone limitations. PMID- 2918889 TI - NIH change procedures for monitoring scientific misconduct. PMID- 2918890 TI - US Congress scuttles federal agency salary increases. PMID- 2918891 TI - First report on US AIDS behavior. PMID- 2918892 TI - Soviet psychiatrists at odds on eve of visit by United States. PMID- 2918893 TI - Too high radon risks not helped by "penny-pinching" UK government. PMID- 2918894 TI - Japan grapples with definition of death by brain death. PMID- 2918895 TI - Multiple sclerosis. Relationship to a retrovirus? PMID- 2918896 TI - Cell growth factors. Bicarbonate and pHi response. PMID- 2918897 TI - Benign familial neonatal convulsions linked to genetic markers on chromosome 20. AB - Recurrent seizures, commonly known as epilepsies, occur in 1.7% of the general population by age 40. The factors that initiate or underlie seizures are not well understood, but trauma, infectious disease and genetics have been implicated. An understanding of the molecular basis of seizures would shed light on the basic mechanisms of neuronal homeostasis and allow new therapeutic strategies to be explored. Here, we report the mapping of an epilepsy gene to a specific chromosomal region, on the basis of cosegregation of two closely-linked DNA markers with a form of epilepsy known as benign familial neonatal convulsions (BFNC2, 12120 in ref. 3). The linked markers confirm the genetic basis and autosomal dominant inheritance of this trait, and localize the gene causing BFNC in this family to the long arm of chromosome 20. This regional placement is the first step towards the isolation of a gene involved in neuronal activity in the human brain. PMID- 2918898 TI - Computer-analysed 2-D electrophoresis. AB - A service is now available for analysing 2-dimensional gels and comparing them to existing databases, broadening the number of laboratories which can study protein expression using the technique. PMID- 2918899 TI - Compensation for haemophiliacs. PMID- 2918900 TI - Embryo research. PMID- 2918901 TI - Generic drug-makers win telling point. PMID- 2918902 TI - Research foundation loses out in fund-raising failures. PMID- 2918903 TI - Truce on the US horizon for engineered organism releases. PMID- 2918904 TI - A nose for Alzheimer's disease? PMID- 2918905 TI - Transatlantic spread of seal virus. PMID- 2918906 TI - Hazards of sulphur. PMID- 2918907 TI - The perception of moving plaids reveals two motion-processing stages. AB - When viewed through a small aperture, the perceived motion exhibited by a long moving line or grating is ambiguous. This situation prevails because even a perfect machine could only detect motion perpendicular to a moving contour, so motion parallel to a contour is undetectable. The human visual system views the world through an aperture array--the neural receptive fields. Therefore a moving object is viewed through many small apertures and the motion within many of those apertures is ambiguous. This ambiguity may be resolved by monitoring the motion of a distinctive feature, such as a line-end or corner, and attributing to the larger object the motion of the feature. Alternatively, Adelson and Movshon have suggested that moving images are processed in two stages, that is, they are first decomposed into one-dimensional components which are later recombined to generate perceived object motion. For a moving plaid, defined as the sum of two drifting gratings, these alternative models generate different predictions concerning the resolution of the plaid's motion ambiguity. A feature monitor would respond to the motion of the intersections between gratings, whereas the two-stage motion processor would first decompose the plaid into its constituent gratings and subsequently recombine them to generate the perception of a moving plaid. Using speed discrimination to distinguish between the two models, I find that discrimination thresholds reflect the speed of a plaid's component gratings, rather than the speed of the plaid itself. This result supports the two-stage model. Although speed discrimination is limited by component processing, observers cannot directly access component speed. The only perceptually accessible velocity signal is generated by the second-stage pattern processing. PMID- 2918908 TI - Direct binding of influenza peptides to class I HLA molecules. AB - Activation of T lymphocytes requires the intracellular fragmentation of foreign antigens and their presentation by class I or class II major histocompatibility complex (MHC) glycoproteins. The direct binding of peptides to class II molecules has been demonstrated using equilibrium dialysis, gel filtration and fluorescence energy transfer at planar membranes, and its specificity compared to that of T cell activation. In contrast, direct binding of peptides to class I molecules has been difficult to detect; although peptide sensitization experiments and the crystallographic structure of HLA-A2 (ref. 9) persuasively argue for its occurrence and importance. Here we describe a gel filtration assay from which we derive direct evidence for selective binding of an influenza matrix peptide to HLA-A2 and for binding of an influenza nucleoprotein peptide to HLA-B37. These two peptides have previously been shown to act respectively as targets for certain HLA-A2 or HLA-B37 restricted influenza-specific cytotoxic T lymphocytes (CTL). In addition we demonstrate binding to some, but not all, HLA allospecificities that cannot present these peptides to CTL. We estimate that less than 0.3% of the HLA molecules present in any given purified preparation were able to bind the added peptides. PMID- 2918909 TI - A pseudo-exon in the functional human alpha A-crystallin gene. AB - The frequent correspondence of exons to structural or functional domains in proteins has suggested that many proteins have evolved by modular assembly. This idea is supported by examples of apparent exon duplication and by shared domains among both alternatively spliced and completely separate genes. During this process it is probable that some combinations of exons would not prove advantageous and would therefore be lost. Here we report that within the active single-copy human gene for alpha A-crystallin there is a 'pseudo-exon' in the early stages of being extinguished, perhaps the result of a failed experiment in the evolution of this specialized, lens-specific protein. PMID- 2918910 TI - Dynamical transition of myoglobin revealed by inelastic neutron scattering. AB - Structural fluctuations in proteins on the picosecond timescale have been studied in considerable detail by theoretical methods such as molecular dynamics simulation, but there exist very few experimental data with which to test the conclusions. We have used the technique of inelastic neutron scattering to investigate atomic motion in hydrated myoglobin over the temperature range 4-350 K and on the molecular dynamics timescale 0.1-100 ps. At temperatures below 180 K myoglobin behaves as a harmonic solid, with essentially only vibrational motion. Above 180 K there is a striking dynamic transition arising from the excitation of nonvibrational motion, which we interpret as corresponding to torsional jumps between states of different energy, with a mean energy asymmetry of 12 kJ mol-1. This extra mobility is reflected in a strong temperature dependence of the mean square atomic displacements, a phenomenon previously observed specifically for the heme iron by Mossbauer spectroscopy, but on a much slower timescale (10(-7) s). It also correlates with a glass-like transition in the hydration shell of myoglobin and with the temperature-dependence of ligand-binding rates at the heme iron, as monitored by flash photolysis. In contrast, the crystal structure of myoglobin determined down to 80 K shows no significant structural transition. The dynamical behaviour we find for myoglobin (and other globular proteins) suggests a coupling of fast local motions to slower collective motions, which is a characteristic feature of other dense glass-forming systems. PMID- 2918911 TI - Apoptosis. PMID- 2918912 TI - Human space flight. PMID- 2918913 TI - Rough justice. PMID- 2918915 TI - How to say sorry graciously. PMID- 2918914 TI - The test of time. PMID- 2918916 TI - Meiosis: initiation of recombination. PMID- 2918917 TI - Chaos: detecting density dependence in imaginary worlds. PMID- 2918918 TI - Hair light guide. PMID- 2918919 TI - Cystic fibrosis. PMID- 2918920 TI - DNA helical repeats. PMID- 2918921 TI - Unhealthy genes. PMID- 2918922 TI - UK animal rights: university building bombed. PMID- 2918923 TI - US animal rights: activists setting the agenda. PMID- 2918924 TI - Identification of a photoreceptor-specific mRNA encoded by the gene responsible for retinal degeneration slow (rds). AB - Mutant mice homozygous for 'retinal degeneration slow' (rds/rds) are characterized phenotypically by abnormal development of photoreceptor outer segments in the retina, followed by gradual degeneration of photoreceptors. This process of degeneration is complete by one year, with preservation of all other retinal cells. The biochemical defect that leads to the mutant phenotype is not known. Our strategy for cloning the rds gene was based upon three previously reported observations. First, the rds locus maps to chromosome 17. Second, experimental rds/rds----+/+ and rds/+----+/+ tetra-parental mice manifest patchy photoreceptor changes in the retina, suggesting that the wild-type rds locus is expressed within cells of the photoreceptor lineage. Finally, the process of degeneration is specific to photoreceptors. On the basis of these observations, we predicted that the rds mRNA is encoded by a gene on chromosome 17 and is normally expressed exclusively within photoreceptors in the retina. We here present evidence that this is the case. PMID- 2918925 TI - Gorbachev's first Chernobyl visit since disaster. PMID- 2918926 TI - Countercurrent chromatography meets MS. AB - Interfacing countercurrent chromatography with thermospray mass spectrometry provides a new analytical tool for detecting nonvolatile, hydrophilic or thermally unstable bioactive natural products. PMID- 2918927 TI - Cattle disease set for cure. PMID- 2918928 TI - Wild chimpanzees endangered. PMID- 2918929 TI - Genome mapping. Europe's plans turn towards talk. PMID- 2918930 TI - Biomedical ethics. French Assembly to lay down the law. PMID- 2918931 TI - The hypothetical way of progress. PMID- 2918932 TI - Polio in Israel. PMID- 2918933 TI - RU 486 abortions. PMID- 2918934 TI - Cancer genetics. Genomic imprinting and embryonal tumours. PMID- 2918935 TI - Lipoprotein receptors. Unravelling atherosclerosis. PMID- 2918936 TI - Preferential mutation of paternally derived RB gene as the initial event in sporadic osteosarcoma. AB - Successive loss of function of both alleles of the retinoblastoma susceptibility gene (RB) on human chromosome 13 seems to be critical in the development of retinoblastoma and osteosarcoma. In cases where the tumour is familial and susceptibility is inherited, a mutation in one of the alleles is carried in the germline. We have recently shown that cytogenetically visible germline mutations are usually in the paternally derived gene. Such a bias would not be expected for sporadic (non-familial) tumours, where both mutations occur in somatic tissue, but there has been some indication of a bias towards initial somatic mutation in the paternally derived gene on chromosome 11 in sporadic Wilms tumour. We have now examined 13 sporadic osteosarcomas and find evidence which indicates that in 12 cases the initial mutation was in the paternal gene, suggesting the involvement of germinal imprinting in producing the differential susceptibility of the two genes to mutation. PMID- 2918937 TI - DNA-protein conjugates can enter mitochondria via the protein import pathway. AB - Mitochondria import most of their proteins and small molecules from the cytoplasm. There is some tentative evidence that they import some of their RNAs, but it is not known how nucleic acids could enter mitochondria. Here, we show that isolated yeast mitochondria can import a single-stranded or double-stranded 24-base pair piece of DNA whose 5' end is covalently linked to the C-terminus of a mitochondrial precursor protein. PMID- 2918939 TI - [Apoplexy: aspects of rehabilitation and prevention. 23 November 1988]. PMID- 2918940 TI - Can we predict outcome in acute renal failure? PMID- 2918938 TI - Reconstruction of an enzyme by domain substitution effectively switches substrate specificity. AB - The polar domains of the two transcarbamoylases, aspartate transcarbamoylase (ATCase) and ornithine transcarbamoylase, (OTCase) from Escherichia coli bind the common substrate carbamoyl phosphate and share extensive amino-acid sequence homology. The equatorial domains of the two enzymes differ in their substrate specificity (ATCase binds aspartate, OTCase binds ornithine) and have decreased sequence identity. While addressing the conservation of specific protein interactions during the evolution of these enzymes, we were able to switch one of their amino-acid-specific equatorial domains to produce a viable chimaeric enzyme. This was achieved by the in vitro fusion of DNA encoding the polar domain of OTCase to DNA encoding the equatorial domain of ATCase. The resulting gene fusion successfully transformed an argI-pyrB deletion strain of E. coli to pyrimidine prototrophy, giving rise to Pyr+ transformants that expressed ATCase but not OTCase activity. The formation of this active chimaeric enzyme shows that by exchanging protein domains between two functionally divergent enzymes we have achieved a switching in substrate specificity. PMID- 2918941 TI - Easy and early prognosis in acute tubular necrosis: a forward analysis of 228 cases. AB - Multiple factors still influence the high rate of mortality in acute tubular necrosis. Trying to analyze the influence of each risk factor present in an individual patient and the possible interdependence between these factors, as well as to obtain an early prognosis, we have applied a forward analysis to demographic data, acute renal failure origin, need of dialysis, diuresis and clinical conditions in 228 patients, using a multiple linear regression model contained in a computer package. Based on this approach we have found that three variables: deep neurological coma, persistent blood hypotension and assisted respiration have significant influence on mortality. Also, a regression equation was obtained which could be applied as a discriminant score to patient prognosis. This score, calculated with the three aforementioned variables and oliguria when the nephrologist sees the patient for the first time, allows an easy and early prognosis in each patient with acute tubular necrosis. PMID- 2918942 TI - Pure mesangial proliferative glomerulonephritis. A clinicomorphologic analysis and its possible role in morphologic transition of minimal change lesion. AB - Renal biopsies from 45 children with idiopathic nephrotic syndrome were analysed. A clinicopathologic correlation has been attempted in 19 children with mesangioproliferative glomerulonephritis. Mesangial hypercellularity is found to have a direct correlation with the clinical presentation, response to therapy and final outcome. The presence of diffuse mesangial IgM or IgM with C3 is of no significance and lacks specificity. PMID- 2918943 TI - Comparative study of C5a plasma levels with different hemodialysis membranes using an enzyme-linked immunosorbent assay. AB - Using a specific and sensitive ELISA for C5a, the present study shows that predialysis levels of C5a in end-stage renal disease patients are not elevated and that all membranes studied (Cuprophan, Hemophan, Gambrane and hydrophilic polysulfone) cause significant increases of C5a plasma levels albeit to different degrees. Higher increases of C5a were accompanied by larger decreases of circulating granulocytes and monocytes. Dialyzers with a newly introduced modified regenerated cellulose membrane, Hemophan, showed lower C5a plasma levels during hemodialysis than Cuprophan. With Hemophan C5a plasma levels were comparable to those with polysulfone membranes. PMID- 2918944 TI - Aluminum removal with hemodialysis, hemofiltration and charcoal hemoperfusion in uremic patients after desferrioxamine infusion. A comparison of efficiency. AB - In order to compare the effectiveness of aluminum removal in uremic patients during extracorporeal treatment, 17 patients with endstage renal failure were given a desferrioxamine infusion of 40 mg/kg body weight after an ordinary dialysis treatment. Forty-eight hours later 7 patients were treated with hemodialysis, 6 with hemofiltration and 4 with a combination of hemodialysis and hemoperfusion. The clearance of aluminum was measured at different intervals. It was found that the aluminum clearance was 75 +/- 18 ml/min in hemofiltration compared to 30 +/- 10 ml/min in hemodialysis (p less than 0.001). A combination of hemodialysis and hemoperfusion with a charcoal column containing 100 g activated charcoal in series gave a total aluminum clearance of 56 +/- 11 ml/min. The total amount of aluminum in the ultrafiltrate after hemofiltration was found to be approximately 3 times as high (1,728 +/- 156 micrograms) as the total amount of aluminum in the hemodialysis water that had passed a single pass system during a 4-hour dialysis (576 +/- 104 micrograms). Our results indicate that hemofiltration or a combination of hemodialysis and hemoperfusion should be used to remove aluminum in patients with signs of severe aluminum accumulation such as encephalopathy or painful bone disease, because these methods are 2-3 times as effective as ordinary hemodialysis. In patients where aluminum has been accumulated but no severe symptoms occur hemodialysis gives a significant clearance of the aluminum desferrioxamine complex. PMID- 2918945 TI - Clinical availability of serum fructosamine measurement in diabetic patients with uremia. Use as a glycemic index in uremic diabetes. AB - Serum fructosamine levels were investigated in patients with uremia undergoing various modes of treatment. The serum fructosamine levels correlated positively with the blood glucose levels determined a week or two earlier. The fructosamine levels were significantly affected by the protein concentration, and those corrected for protein concentrations had a closer correlation to the blood glucose levels than did the uncorrected levels. The corrected fructosamine levels were not significantly different between healthy volunteers and nondiabetic patients with uremia on conservative treatment. In an in vitro system, fructosamine concentrations were hardly affected by urea, which is known to influence the level of hemoglobin A1. These results suggest that serum fructosamine measurement can provide us with reliable information on a short-term glycemic condition, even in azotemic patients. To be more precise, the serum level of fructosamine corrected for protein concentration can be an excellent glycemic index which is not susceptible to over- or dehydration and is of high clinical value, especially in the management of diabetic patients with chronic renal failure. PMID- 2918947 TI - Effects of L-carnitine administration on short-chain fatty acid (acetic acid) and long-chain fatty acid metabolism during hemodialysis. AB - The purpose of the study is to investigate the effects of L-carnitine on the exogenous acetate metabolism during hemodialysis together with the triglyceride and free fatty acid metabolism. Sixteen chronic renal failure patients on acetate dialysis were orally administered 1,200 mg of L-carnitine chloride per day for 12 weeks. Plasma triglyceride concentrations at 30 and 60 min following initiation of hemodialysis were significantly lower than before hemodialysis, while the plasma concentrations of free fatty acid at the same points into hemodialysis were significantly higher than before hemodialysis, whether L-carnitine chloride was being given or not. This is attributed to the enhanced degradation of triglyceride and the increased generation of the free fatty acid with heparin administration during hemodialysis. The L-carnitine chloride treatment did not affect the plasma triglyceride concentrations at 30 and 60 min into hemodialysis, whereas the free fatty acid concentrations at the same points into hemodialysis were significantly lower after L-carnitine chloride administration commenced than before it. This is attributed to the fact that fatty acid oxidation was enhanced following the L-carnitine chloride treatment. Compared to before the drug administration, the whole body clearance of exogenous acetate was significantly increased after the drug was given, and the plasma acetate level during hemodialysis fell accordingly. This is attributed to the fact that with L carnitine chloride administration, the amount of accumulated acyl-CoA in the cytosol decreased and consequently the citrate cycle function increased. PMID- 2918946 TI - Free and sulfoconjugated catecholamines in normotensive uremic patients: effects of hemodialysis. AB - In 9 normotensive uremic patients undergoing chronic hemodialysis, the baseline plasma catecholamines varied widely from low-normal to very high; sulfoconjugated plasma catecholamines were constantly high. A dialysis-induced fall of all sulfated catecholamines and epinephrine was observed. Norepinephrine decreased in 5 patients and increased in 4, with a strong inverse correlation between predialysis norepinephrine and delta norepinephrine (p less than 0.0001). No correlation was evident between clinical parameters (mean arterial pressure, heart rate) and catecholamines (both predialysis and postdialysis). Significant (p less than 0.0001 and p less than 0.0002) inverse correlations between epinephrine and norepinephrine and their sulfoconjugation degree were demonstrated only in predialysis. Our data may support the presence of a uremic autonomic neuropathy and adrenoceptor damage. PMID- 2918948 TI - Studies of a glomerular permeability factor in patients with minimal-change nephrotic syndrome. AB - Peripheral blood mononuclear cells (PBMC) from patients with minimal-change nephrotic syndrome (MCNS) were tested for their ability to produce a factor which increases the urinary protein excretion levels of rats. It was shown that enhanced proteinuria can be produced in 8-hour urine specimens from rats by the injection of concentrated supernatants of cultured concanavalin-A-stimulated PBMC of patients with MCNS, but not from other nephrotics or normal subjects. The increase in urinary protein excretion was associated with a significant alteration of glomerular epithelial cells similar to that seen in MCNS. These results suggest that in MCNS, PBMC release a factor, which we termed a glomerular permeability factor (GPF), causing changes in glomerular permeability with resulting proteinuria. PMID- 2918949 TI - Body composition changes in the subtotally nephrectomized rat fed differing dietary proteins. AB - Changes in body composition are found in chronic uraemia, but it is unclear if this results from poor nutrient intake or is a consequence of impaired renal function. To investigate this question, 31 female Wistar rats were allocated to undergo subtotal nephrectomy or sham operation and were fed diets of either 24% casein or 24% soya protein. Three months later measurements of inulin clearance were undertaken in the conscious animal and the carcass subsequently analyzed for body water and body fat. Subtotally nephrectomized animals had a significantly greater proportion of body water (p less than 0.001) and a lesser proportion of body fat (p less than 0.001) than control animals, and a significant correlation was found between glomerular filtration rate and body fat content (24% casein diet: r = 0.96; 24% soya diet: r = 0.71). The dietary protein source appeared not to influence the body composition. These results support the concept that altered body composition in uraemia is due to renal dysfunction rather than altered nutrient intake. PMID- 2918950 TI - Comparison of toxic effects of methylguanidine, guanidinosuccinic acid and creatinine in rats with adenine-induced chronic renal failure. AB - Methylguanidine (MG), guanidinosuccinic acid (GSA) and creatinine (Cr), which accumulate in the body in parallel with the progress of renal failure after adenine administration, were given separately to rats in order to compare their toxicities. Food containing adenine was given to rats for 24 days to induce renal failure, and then each of the test substances was administered intraperitoneally from the following day, the survival rates of the rats being subsequently determined. Administration of MG at varying doses produced a dose-dependent decrease in the survival rate, whereas the survival curves obtained for rats given GSA or Cr indicated weak toxicity. The levels of MG, GSA or Cr accumulated in the body were extraordinarily high in surviving rats after 14 days of administration of each respective compound. The toxic effects are discussed on the basis of these results. PMID- 2918951 TI - Acquired renal cysts in five-sixths nephrectomized rats: the roles of oxalate deposits in renal tubules and a renotropic factor. AB - The present study was undertaken to see if the oxalate deposits seen in renal tubules are a causative factor in the development of acquired renal cysts in chronic renal failure. Thirty 5/6 nephrectomized rats had free access to water containing 8 mg/ml of vitamin C (oxalate precursor) and 20 5/6 nephrectomized rats were given tap water without vitamin C. Oxalate deposits were found on microscopy in the renal tubules of vitamin C-treated rats in the 11th and 12th postnephrectomy months; however, acquired renal cysts were noted far in advance of the appearance of oxalate crystals. It has been suggested that the tubular dilatation seen in 5/6 nephrectomized rats is caused by an abrupt decrease in the functioning renal mass, leading to the production of a so-called 'renotropic factor'. However, oxalate deposits and renal tubular dilatation in oxalate treated 5/6 nephrectomized rats preceded the renal tubular dilatation of untreated partially nephrectomized rats. In addition, these histological changes in the kidney were also seen in healthy rats which were given oxalate orally and subcutaneously. The present study suggested that the pathogenesis of acquired renal cysts is multifactorial. Renotropic factor may play an important role leading to nephron hyperplasia, but oxalate deposits in the renal tubules seem to be an important factor in the formation of these cysts. PMID- 2918952 TI - Normalization of renal function and blood pressure after dissolution with intra arterial fibrinolytics of a massive renal artery embolism to a solitary functioning kidney. AB - The intra-arterial administration of fibrinolytics in a massive embolism to the renal artery of a solitary functioning kidney determined quick normalization of the severe renal failure and hypertension. PMID- 2918953 TI - Association of IgA nephropathy and myasthenia gravis. AB - Three patients with IgA nephropathy associated with myasthenia gravis are described. In all 3 cases, myasthenia gravis emerged after the discovery of glomerulonephritis. Myasthenic symptoms were improved by thymectomy in 2 cases, but progression of the renal disease was not improved. Some systemic abnormalities, including immunological aberrations, were observed in these two disorders. It is postulated that T cell abnormalities in IgA nephropathy might be independent of the development of myasthenia gravis. PMID- 2918954 TI - Carbamazepine-induced granulomatous necrotizing angiitis with acute renal failure. AB - A 42-year-old male treated with carbamazepine developed a skin eruption in the trunk, followed by acute renal failure. Laboratory data revealed leukocytosis (15,700/mm3) with eosinophilia (37%). A renal biopsy disclosed granulomatous necrotizing angiitis that differed from classic periateritis nodosa and hypersensitivity angiitis. All drugs were discontinued immediately, and there was a gradual improvement of the renal function. A carefully performed provocation test using carbamazepine was positive. We made a diagnosis of carbamazepine induced granulomatous necrotizing angiitis. Only 6 cases of drug-induced granulomatous angiitis have been reported prior to the present case. Drug-induced granulomatous angiitis is often fatal. The present report suggests the importance of making a diagnosis quickly, and providing adequate treatment in order to prevent a fatal course. PMID- 2918955 TI - Acute renal failure after high-dose methotrexate therapy. Role of hemodialysis and plasma exchange in methotrexate removal. PMID- 2918956 TI - Spicular cap of amyloid on the outer aspect of the Bowman's capsule. PMID- 2918957 TI - Does lead overload develop in hemodialysis patients? PMID- 2918958 TI - Erythrocyte charge, glycosaminoglycans and diabetic nephropathy. PMID- 2918959 TI - Erythropoietin treatment: influence of haemoglobin concentration on dialyser creatinine clearance in haemodialysed patients. PMID- 2918960 TI - Clinical significance of an impaired mononuclear phagocyte system immune clearance in human nephritis. PMID- 2918961 TI - Erythropoietin-associated hypertension: what role for blood viscosity changes? PMID- 2918963 TI - Membranoproliferative glomerulonephritis in Japan. PMID- 2918962 TI - Early tubular functional changes in autosomal dominant polycystic kidney disease. PMID- 2918964 TI - Berger's disease without IgA deposits? PMID- 2918965 TI - Relapsing acute renal failure in IgA nephropathy. PMID- 2918966 TI - Acute renal failure in multiple myeloma after the ingestion of a contrast agent for cholecystography. PMID- 2918967 TI - Hypernatremia associated with severe rhabdomyolysis. PMID- 2918968 TI - A trial of the 21-aminosteroid U74006F in a primate model of chronic cerebral vasospasm. AB - The efficacy of U74006F in the prophylaxis of chronic cerebral vasospasm (VSP) was evaluated in a randomized, double-blind, placebo-controlled trial. Forty cynomolgus monkeys were divided by restricted randomization into 2 treatment groups of 20. Five animals from each treatment group were randomized into subgroups 1 and 2. The animals of subgroup 1 were studied pathologically. Brain biopsies of the animals in subgroup 2 were performed and studied with high performance liquid chromatography (HPLC). The remaining 20 animals supplemented the number studied angiographically. Significant VSP (P less than 0.05) was detected in the majority of vessels from the clot site (right) of both treatment groups. Electron microscopy results showed positive correlation with the angiographic data. When comparing the effects of U74006F to those of the placebo at day 7, there was a significant difference (P less than 0.05) in the degree of VSP in the right extradural internal carotid and right middle cerebral arteries. This resulted from a greater degree of VSP in placebo animals. Two animals developed delayed ischemic deficits, one from each group. The infarct of the U74006F animal was smaller than the infarct in the placebo animal. Although overall changes in phosphagen levels did not reach statistical significance, HPLC analysis of the cortical biopsies did show a decrease in the ATP/ADP +/- AMP ratio of 54% in placebo animals and only 7% in animals receiving U74006F. The middle cerebral arteries of 2 animals were also studied with HPLC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918969 TI - The importance of "accessory" outflow pathways in hydrocephalus after experimental subarachnoid hemorrhage. AB - This study evaluated the changes in pathways of cerebrospinal fluid (CSF) outflow that accompanied acute and compensated hydrocephalus in the rabbit. Intraventricularly injected 99mTc antimony sulfide was used as a tracer of outflow pathways, and specified structures were counted 12 to 24 hours after injection. Fifteen rabbits were divided into three groups: 1) an acutely hydrocephalic group in which 3 cisternal injections of blood were followed by a study of CSF pressure, ventricular size, and CSF outflow pathways 1 week after the last injection; 2) a control group treated according to the same protocol, except that sterile saline was injected instead of blood; and 3) a chronic group also treated according to the same protocol but in which the animals were maintained an average of 4 weeks after the last blood injection. Ventricular size was measured by computed digitation and expressed as an area ratio of ventricle to brain (VBR). In control animals, 11.8% of the injected colloid dosage was found in cranial perineural lymphatic channels, and 4.8% appeared in the spinal cord. The mean CSF pressure was 149 +/- 20.2 mm H20 (mean +/- SE) and the mean VBR was 0.040 +/- 0.003. In animals evaluated 1 week after subarachnoid injection, accessory cranial perineural lymphatic outflow decreased significantly to 3.4%, and spinal cord activity increased to 9.8% (P less than 0.05, two-tailed t-test). These animals were hydrocephalic and had CSF pressure of 247 +/- 25.1 mm H20 (mean +/- SE) and VBR of 0.083 +/- 0.009.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2918970 TI - Evaluation of prognostic factors in cerebral arteriovenous malformations. AB - In a retrospective study of 48 patients who underwent elective surgery for cerebral arteriovenous malformations, a statistical analysis of demographic, clinical, and neuroradiological data was undertaken in order to discover the best predictors of operative morbidity. In addition, the predictive value of different clinical grading systems as applied to this series was compared. All patients had a computed tomographic scan and a positive angiogram before surgery. Complete resection was proven angiographically. The univariate Mann-Whitney-Wilcoxon rank sum test, the Fisher exact test, Spearman's rank correlation coefficient analysis, and multivariate logistic regression were used as statistical methods. Duration of surgery, the development, of either new deficits or an increase in the preoperative neurological signs immediately after surgery, and rehabilitation (as measured by the Karnofsky index) were taken as target variables for the difficulty of operation and for postoperative morbidity, respectively. The largest diameter of the nidus of the arteriovenous malformation, eloquence of the adjacent brain, and deep venous drainage showed the most consistent correlation with these target variables. Intracerebral hematoma and other single factors, such as the age of the patient or localization of the arteriovenous malformation did not affect the outcome. The clinical grading scale of Spetzler and Martin provided better prediction of surgical risks than other proposed systems. PMID- 2918971 TI - Impairment of vertebral artery flow caused by extrinsic lesions. AB - In a consecutive series of 71 cases of extrinsic lesions involving the vertebral artery (VA), 51 patients presented with external compression of this vessel. The compressive agents included 34 tumors, 4 osteophytes, 5 fibrous bands, 4 traumatic lesions, 2 neural elements, and 2 infectious processes. The main site was the second portion of the VA (C2-C6) (30 of 51 patients). Compression always induced at least significant stenosis, and in 8 patients caused complete occlusion. The compression was either permanent (44 patients) or intermittent (7 patients). Symptoms were observed in 11 patients, including 2 with permanent deficits. Surgical release of compression was performed each time symptoms could be explained by a reduction in VA flow and also when the compressing agent needed to be removed, as in the cases involving tumors. VA decompression was achieved by direct approach in 37 patients, by reduction and fixation of a traumatic dislocation in 2 patients, and by distal revascularization in 4 patients. Medical treatment or roentgenotherapy was used in the other patients. Results were excellent in all but 2 patients, who died from traumatic and ischemic lesions, respectively. Therefore, it seems important to identify external causes of compression of the VA for two reasons: 1) to suppress symptoms of vertebrobasilar insufficiency when their relation to VA compression is clearly established, and 2) to remove compressive agents like tumors safely while preserving the VA. PMID- 2918972 TI - Critical analysis of extensive cervical laminectomy. AB - Conventional extensive laminectomy has been widely performed to reduce spinal cord compression, and is greatly facilitated by the use of an air drill. Laminectomy is recognized, however, as the occasional cause of problems after surgery, such as spinal instability or deformity, acceleration of spondylotic change, constriction of the dura mater caused by extradural scar formation, and lack of posterior bony protection for the spinal cord. In an effort to eliminate these negative aspects of conventional laminectomy, a surgical technique called suspension laminotomy has been used. Fifty-five patients treated with conventional extensive laminectomy and 55 others treated with suspension laminotomy were followed up clinically and compared. Flexibility and alignment of the cervical spine were assessed by plane radiographs, and dural configuration by computed tomographic scans. Neurologic improvement was also evaluated. Decrease of spinal movement after laminectomy was observed, notably during extension, probably as a result of functional insufficiency of paraspinal muscles. The incidence of postoperative spinal deformity was lower and the relief of dural constriction better in the patients treated with suspension laminotomy than in those treated with conventional laminectomy. Neurological recovery was significantly better in fully decompressed cases than in insufficiently decompressed cases. PMID- 2918973 TI - Magnetic resonance imaging after closed head injury in children. AB - Magnetic resonance imaging (MRI) was performed in a series of 21 children and adolescents who had been hospitalized after sustaining closed head injuries of varying severity at least 6 months previously. Areas of high intensity in the parenchyma were present in 8 of the 11 severely injured patients, whereas MRI findings were normal in all 10 patients with mild-to-moderate head injuries. Lesions involving the subcortical white matter were confined to severely injured patients whose clinical features were compatible with diffuse axonal injury. Neuropsychological assessment disclosed deficits primarily in the severely injured patients; these deficits were significantly associated with persistent lesions visualized by MRI. Serial MRI and neurobehavioral assessment following early injury may be useful in documenting cognitive impairment in relation to structural alterations of the young brain. PMID- 2918974 TI - Control of intractable spasticity with intrathecal morphine sulfate. AB - Three years ago we reported our preliminary results regarding treatment of intractable spasticity with use of intrathecal morphine. This paper is a follow up report of 12 patients who underwent implantation of a pump or reservoir for delivery of intrathecal morphine sulfate for control of spasticity. Our primary concern initially was that patients would ultimately become drug tolerant and lose the beneficial effect of the morphine. Only one of these 12 patients has developed drug tolerance. The longest follow-up period has been 4.3 years, and this patient has maintained excellent control of his spasticity with a stable dose of 2 mg of morphine daily. PMID- 2918975 TI - Effects of hypovolemic hypotensive shock on somatosensory and motor evoked potentials. AB - The utility of evoked potentials in monitoring spinal cord and cerebral function in various neurosurgical and orthopedic operations has now been established. To study the effects of graded hypotension upon spinal and cortical somatosensory evoked potentials (SMEPs), and spinal motor evoked potentials (SMEPs), 12 anesthetized cats were subjected to graded hypotension ranging from a mean arterial blood pressure of 100 mmHg to 30 mmHg or less. Hypotension causes a progressive increase in onset latency and a decrease in amplitude and conduction velocity of SEPs and SMEPs. Cortical SEPs and SMEPs were sensitive to profound hypotension (MAP less than 30 mmHg). Spinal SEPs showed more resistance and disappeared at lower levels of hypotension. Immediate blood transfusion caused resumption of cortical SEPs and SMEPs within 30 minutes after infusion; however, the latency and amplitude of responses did not reach the baseline values within 1 hour after transfusion. The sequential recovery of evoked responses was dependent upon the length of hypotension. When 15 minutes elapsed between loss of responses and transfusion, cortical SEPs and SMEPs did not resume within 1 hour after infusion. No return of signals occurred if 30 minutes elapsed between the loss of evoked responses and blood reperfusion. These findings suggest that ischemia associated with profound systemic hypotension can alter or obliterate evoked responses. PMID- 2918976 TI - Influence of anesthetics--nitrous oxide in particular--on electromyographic response evoked by transcranial electrical stimulation of the cortex. AB - The influence of anesthetics usually used for neuroleptic anesthesia--nitrous oxide, fetanyl, flunitrazepam, and thiopental sodium--on motor evoked potentials (MEP) was examined in 15 patients during neurosurgical operations on the spinal cord, in 16 patients in traumatic coma, and in 6 healthy volunteers. MEP were recorded from the contralateral thenar and anterior tibial muscles in response to single transcranial electrical stimuli on the motor cortex. Intraoperatively, during neuroleptic anesthesia we found the amplitudes to be reduced to an average of 11% of the preoperative baselines for the thenar potentials, and to 7% of the preoperative baselines for the anterior tibial muscle potentials, despite a maximum stimulus strength of 750 V. A similar reduction of MEP amplitudes was observed in 6 volunteers during breathing of an oxygen/nitrous oxide mixture (34%/66%), whereas fentanyl, flunitrazepam, and thiopental had only a minor effect on MEP. We conclude that with respect to anesthesia-related suppression of amplitudes, an average of 5 to 15 electromyographic responses should be evaluated for intraoperative monitoring of MEP using the technique described here. PMID- 2918977 TI - Does intraoperative monitoring of auditory evoked potentials reduce incidence of hearing loss as a complication of microvascular decompression of cranial nerves? AB - During a 14-month period, 129 individuals underwent 140 operations for microvascular decompression to relieve hemifacial spasm, disabling positional vertigo, tinnitus, or trigeminal neuralgia at our institution. Seven patients were operated upon twice on the same side and 4 were operated upon on both sides at different times. In each case, the brainstem auditory evoked potentials were monitored intraoperatively by the same neurophysiologist. In 75 of these operations, compound action potentials were also recorded from the exposed 8th nerve. Comparison of speech discrimination scores before the operation and at the time of discharge showed that at discharge, discrimination had decreased in 7 patients by 15% or more and increased in 4 patients by 15% or more, in 2 patients by as much as 52%. Essentially similar results were obtained when preoperative speech discrimination scores were compared with results obtained from the 87 patients who returned for a follow-up visit between 3 and 6 months after discharge. Only one patient lost hearing (during a second operation to relieve hemifacial spasm). Another patient (also operated upon to relieve hemifacial spasm) suffered noticeable hearing loss postoperatively, but had recovered nearly normal hearing by 4 months after the operation. Nine patients had an average elevation of the hearing threshold for pure tones in the speech frequency range (500 to 2000 Hz) of 11 dB or more at 4 to 5 days after the operation; 8 of these had fluid in their middle ears that most likely contributed to the hearing loss. Threshold elevations occurred at 4000 Hz and 8000 Hz in 19 and 29 ears, respectively. PMID- 2918978 TI - Ruptured S1-S2 disc presenting with S2 radiculopathy. AB - We report the case of a 61-year-old man in whom numbness developed on the right side of the penis, scrotum, and perineum after he jumped into a swimming pool. Magnetic resonance imaging and a computed tomographic scan disclosed a lesion at S1-S2 impinging on the right S2 nerve root. At surgery, ruptured disc material originating in an area normally occupied by the fixed fibrocartilaginous plate was identified and excised. Postoperatively, the numbness resolved. We discuss a possible cause of the rupturing of the sacral disc and recommended treatment by laminectomy and excision, as in other cases of ruptured disc at other levels of the spinal column. PMID- 2918979 TI - Aneurysmal bone cyst of the thoracic spine: treatment by excision and segmental stabilization with Luque rods. AB - Preoperative radiological evaluation with magnetic resonance imaging and computed tomography was valuable in planning the surgical management of a destructive lesion of the posterior elements of the thoracic spine that was causing spinal cord compression in an 18-year-old woman. Preoperative recognition of bilateral involvement of the pedicles in addition to the laminae and spinous process led to use of prophylactic segmental stabilization of the spine with Luque rods after successful excision of an aneurysmal bone cyst. This case provides an example of the usefulness of computed tomographic scanning and magnetic resonance imaging in assessing the distribution and location of vertebral tumor and its potential effect on spinal stability. The efficacy of combining radical excision with stabilization for treatment of aneurysmal bone cysts of the spine is emphasized. PMID- 2918980 TI - Magnetic resonance imaging of symptomatic Rathke's cleft cyst: report of a case. AB - A case of symptomatic Rathke's cleft cyst is described. In spite of the intrasellar component and radiological and clinical evidence of involvement of the pituitary gland, the sella turcica was minimally involved. MRI afforded optimal visualization and localization of the intra- and suprasellar components vis-a-vis the pituitary gland, optic chiasm, infundibular stalk, and carotid arteries. PMID- 2918981 TI - Ectopic prolactinoma within the sphenoid sinus. AB - A case of an ectopic prolactin-producing tumor located within the sphenoid sinus is reported. It was discovered in a girl who experienced secondary amenorrhea without galactorrhea. We discuss the different diagnoses proposed before immunocytochemical staining results were available. This case presented unusual radiological, surgical, and histopathological aspects. PMID- 2918982 TI - Progressive unilateral hydrocephalus in adults. AB - Unilateral dilatation of the lateral ventricle in adults is rare. We report 2 cases of unilateral hydrocephalus with obstruction at the foramen of Monro. Both patients presented with symptoms of raised intracranial pressure. PMID- 2918983 TI - Upward transtentorial herniation: a complication of postoperative edema at the cervicomedullary junction. AB - Local edema at the operative bed developed a few hours after uneventful subtotal removal of a lesion occupying the lower medulla and upper cervical cord. The patient experienced apnea, quadriplegia, and circulatory collapse followed by acute respiratory insufficiency. Hydrocephalus secondary to aqueductal occlusion occurred on the 3rd postoperative day. A computerized tomographic scan was compatible with upward transtentorial herniation. The association of this phenomenon with an intra-axial lesion at the cervicomedullary junction has not been previously documented. The pathophysiological mechanisms implicated in this complication are discussed. PMID- 2918985 TI - Modified skull clamp procedure. PMID- 2918984 TI - Cerebellar hemangioblastoma during pregnancy. PMID- 2918986 TI - Temporary lumbar drainage in normal pressure hydrocephalus. PMID- 2918987 TI - Therapeutic trial of intravenous nimodipine. PMID- 2918988 TI - Origin of motor evoked potentials in the rat. PMID- 2918989 TI - Neurography for intraoperative monitoring of facial nerve function. PMID- 2918990 TI - Vasoactive intestinal peptide (VIP)-like immunoreactive neurons located in the rat suprachiasmatic nucleus receive a direct retinal projection. AB - The existence of a direct projection from retinal ganglion cells to vasoactive intestinal peptide (VIP)-like immunoreactive neuronal elements in the rat suprachiasmatic nucleus (SCN) was revealed by combining analysis of degenerating axons following enucleation and electron microscopic immunocytochemistry. Degenerating axons appeared to make synaptic contact with VIP-like immunoreactive dendrite and neuronal perikarya in the ventral part of the SCN. The possibility of neuronal input from retinal ganglion cells to axons of VIP-like immunoreactive neurons was also suspected since axo-axonic synapses were detected between degenerating axons and axons with VIP-like immunoreactivity. Thus, VIP-like immunoreactive neurons in the SCN receive several neuronal inputs, including those from the retina, and may play a significant role in circadian entrainment. PMID- 2918991 TI - Re-evaluation of the effects of norepinephrine on the single-unit activity of paraventricular neurosecretory neurons. AB - Electrical stimulation of the A1 noradrenergic region elicited predominantly an excitatory orthodromic response from paraventricular neurosecretory neurons recorded in urethane-anesthetized male rats. In a majority of cases, locally applied norepinephrine (NE) as well as A1 region stimulation excited paraventricular neurosecretory neurons. However, in some neurons including a subpopulation of putative vasopressin neurons, iontophoresed NE was inhibitory. Both excitatory and inhibitory effects of NE were selectively blocked by the alpha-antagonist, phentolamine, but not by the beta-antagonist, timolol. In general, the results support the notion that the A1 noradrenergic input to paraventricular neurosecretory neurons is excitatory. Nevertheless, the results do not exclude the possibility that NE exerts a specific, alpha-receptor mediated, inhibitory effect on a subpopulation of paraventricular neurons. PMID- 2918992 TI - Receptor position, not nerve branch, determines electroreceptor somatotopy in the gymnotiform fish (Apteronotus leptorhynchus). AB - The supraorbital (SO) nerve branch of some weakly electric teleosts innervates electroreceptors on the entire rostral snout and therefore excludes the infraorbital (IO) branch. A ventral twig of SO innervates the ventral snout (normally IO territory) and projects into the electroreceptive lateral line lobe in an IO pattern. This suggests that afferents to adjacent snout receptors can take widely divergent pathways (different nerve branches) to the electrosensory lateral line lobe (ELL) yet retain somatotopy centrally. We conclude: (1) that there is intrabranch somatotopy within these nerves, and (2) that receptor position, not nerve branch, determines ELL somatotopy. PMID- 2918993 TI - Collateral nerve sprouting and twitch forces of single motor units in conditions with partial denervation in man. AB - Single motor units (MUs) were studied in the first dorsal interosseus muscle of 7 patients with slight partial denervation and in 10 controls. MU action potentials were recorded using the macro-EMG technique and their size was taken to assess collateral nerve sprouting. Simultaneously, the muscle force was monitored to determine the voluntary recruitment thresholds of the MUs and spike-triggered averaging was applied to measure their twitch forces. At comparable force recruitment thresholds, both macro-EMG potentials and twitch forces were increased in the patients. We conclude, that collateral nerve sprouting increases MU force and can compensate for MU loss. PMID- 2918994 TI - An in vitro preparation for studying motor pattern generation in the cerebellorubrospinal circuit of the turtle. AB - In vivo studies in mammals have suggested that the cerebellorubrospinal circuit functions as a recurrent excitatory loop that generates motor commands and transmits them to the spinal cord via the rubrospinal pathway. Here we describe an in vitro preparation from the turtle exhibiting functional synaptic connections between the cerebellum, brainstem and upper spinal cord that is suitable for detailed analysis of this circuit. Electrical stimulation of the spinal cord was used to activate the cerebellorubrospinal circuit while activity was sampled with extracellular recordings from single cells in the red nucleus. Single units responded to stimulation with short and long latency synaptic responses, in addition to antidromic activation. Some cells showed bursts of activity lasting several hundred milliseconds suggesting the presence of recurrent excitation. Interruption of Purkinje cell inhibitory input impinging on the cerebellorubrospinal loop prolonged bursting and enhanced spontaneous activity. This preparation should facilitate the examination of the role of the cerebellorubrospinal circuit in motor pattern generation. PMID- 2918995 TI - Presynaptic effect of gamma-aminobutyric acid on the inhibitory nerve and nerve terminals in the crayfish neuromuscular junction. AB - Experiments were carried out in voltage-clamped fibres of the opener muscle of the first walking leg or claw of small crayfish. Repetitive discharges in the inhibitory nerve innervating the muscle were induced by adding serotonin (10(-6) mol/l) and forskolin (10(-4) mol/l) to the superfusate. Rates of nerve discharge were determined by recording nerve evoked inhibitory postsynaptic currents (IPSCs) in the voltage-clamped muscle fibre. Subsequently, the effect of gamma aminobutyric acid (GABA) on the rate of IPSCs in normal and Cl- -deficient superfusate was investigated. In normal superfusate GABA (10(-5) mol/l) abolished the IPSCs whereas in Cl- -deficient superfusate GABA (10(-4) mol/l) enhanced the rate of IPSCs. Moreover, in Cl- -deficient superfusate the rate of asynchronous quantal release of inhibitory transmitter could be enhanced by GABA. The results indicate that in the crayfish neuromuscular junction the inhibitory axon is supplied with GABA receptors which may affect (a) axonal excitation and (b) quantal output at the inhibitory axon terminals. PMID- 2918996 TI - Long-term potentiation induced in dendrites separated from rat's CA1 pyramidal somata does not establish a late phase. AB - In 14 transversal hippocampal slices from rats the extracellular field-EPSP (excitatory postsynaptic potential) in the dendritic region of the CA1 subfield was recorded after isolating the apical dendrites from their somata by microsurgical cuts through the proximal stratum radiatum. Contrary to intact slices which, after tetanic stimulation of the Schaffer collaterals, showed long term potentiation (LTP) until the end of registration after 8-10 h, LTP declined in the isolated dendrites to baseline values after 3 h. It is concluded that de novo protein synthesis in postsynaptic cell bodies might be necessary for the maintenance of late phases of LTP. PMID- 2918997 TI - Effects of melatonin on neuronal activity in the rat suprachiasmatic nucleus in vitro. AB - The pineal hormone melatonin is believed to act directly on the hypothalamic suprachiasmatic nuclei (SCN), which are principal circadian pacemakers in rodents, although direct demonstration of this is lacking. To determine whether the SCN are sensitive to melatonin electrophysiologically, we investigated the effect of melatonin on rat SCN single-unit activity in an in vitro hypothalamic slice preparation. SCN single-unit activity was inhibited by melatonin superfusion during the late subjective day in a dose-dependent manner but not at other times of day, supporting the view that melatonin acts directly on SCN neurons. PMID- 2918998 TI - The recording of brain evoked potentials resulting from intra-articular focused ultrasonic stimulation: a new experimental model for investigating joint pain in humans. AB - Pain was induced in the proximal interphalangeal joint of the index finger in human volunteers using a high powered focused ultrasonic generator. Eighty, 100 ms pulses were applied during each test. This test was repeated at hourly intervals for a period of 5 h. A brain evoked potential with a characteristic wave form was recorded, resulting from the application of these stimuli. A computerised visual analogue scale system was used to measure subject's perception of the painfulness of each stimulus. A significant correlation was found between evoked potential amplitude and mean visual analogue scale score. There was some variation in evoked potential amplitude and mean visual analogue scale score as a result of repeated application of the test but this was not significant over the 5 h time period. PMID- 2918999 TI - Antagonism of cholecystokinin function in the rostral and caudal nucleus accumbens: differential effects on brain stimulation reward. AB - Microinjections of proglumide, a cholecystokinin (CCK) receptor antagonist, into the rostral and caudal nucleus accumbens (NA) were examined for effects on intracranial self-stimulation (ICSS) derived from the ventral tegmental area (VTA). Proglumide was found to dose-dependently antagonize ICSS when administered in the caudal NA but had weak facilitatory effects when administered in the rostral NA. These findings were interpreted to suggest that endogenous CCK is involved in the neurochemical mechanisms underlying brain stimulation reward derived from the VTA. The present results are consistent with the notion that caudal NA CCK function is associated with facilitatory influences on brain stimulation reward. The dopamine antagonist-like effects of CCK appear to involve CCK actions in the more rostral regions of the NA and may reflect the contribution of non-dopamine neuron-derived source(s) of CCK. PMID- 2919000 TI - Status epilepticus-induced hippocampal damage is modulated by glucose availability. AB - Kainic acid administration induces status epilepticus seizures in the rat which damage CA1 and CA3 hippocampal neurons. Rats made hypoglycemic prior to seizure had enhanced volumes of damage, when compared to normo- or hyperglycemic rats. The mild hypoglycemia was not in the range which, itself, typically produces hippocampal damage. This suggests that limited energy availability compromised the ability of neurons to survive seizures. Our data also suggest that the CA1 damage seen after status epilepticus is not hypoxic-ischemic in origin, since elevating pre-seizure glucose concentrations to a range which typically exacerbates hypoxic-ischemic CA1 damage did not augment status-epilepticus CA1 damage. PMID- 2919001 TI - The amygdala directly innervates adrenergic (C1) neurons in the ventrolateral medulla in the rat. AB - The innervation of adrenergic (C1) neurons in the ventrolateral medulla by the central amygdaloid nucleus (Ce) was investigated using immunohistochemical detection of phenylethanolamine N-methyltransferase (PNMT) combined with anterograde tracing through Phaseolus vulgaris leucoagglutinin (PHA-L) transport and lesion-induced axonal degeneration. Injections of PHA-L into the medial Ce labelled axons in close proximity to PNMT-immunoreactive dendrites and somata in the ventrolateral medulla. The PNMT-immunoreactive neurons within the rostral part of the nucleus reticularis rostroventrolateralis were preferentially innervated by the amygdaloid terminals. Degenerating terminals formed synaptic contacts on PNMT-immunoreactive cells of the ventrolateral medulla in animals with lesions of the Ce. The synaptic contacts were mainly found on dendrites and were usually of the symmetrical type. The present findings provide evidence that cells within the amygdala directly innervate presumed adrenergic cells in the ventrolateral medulla. This pathway may be part of the anatomical substrates that are activated during amygdaloid-mediated sympathetic activity. PMID- 2919002 TI - Passive electrical properties of spontaneously active neurons in the nucleus reticularis gigantocellularis of the cat. AB - We evaluated in chloralose-urethane anesthetized cats the passive electrical properties of 25 spontaneously active neurons in the nucleus reticularis gigantocellularis (NRGC) of the medulla oblongata. Compared to other mammalian brain regions, these reticular cells in general possessed higher input resistance, shorter membrane time constant and first equalizing time constant, and longer somatodendritic electrotonic length factor. It is discussed that, by providing a synaptic machinery for quick and sensitive response to afferent inputs and an efficacious interplay between temporal and spatial summation, these electrical membrane properties may account for the spontaneous and irregular discharge pattern characteristic of the NRGC neurons. PMID- 2919003 TI - Aging does not alter the voltage-dependent release of endogenous dopamine from mouse striatal synaptosomes. AB - Striatal synaptosomes isolated from 3-, 12-, and 24-month-old C57B1/6J mice were exposed to low (5 mM) and high (30 mM) concentrations of potassium of 1, 3, 5, 15 and 30 s. There were no age-related differences in the total intrasynaptosomal content of dopamine among the three age groups of mice. The basal release of endogenous dopamine from synaptosomes isolated from 24-month-old animals was significantly greater than that from synaptosomes isolated from 3-month-old animals at all time points tested. Similarly the potassium stimulated release of dopamine from 24-month-old animals was also higher than that from the 3-month-old group, but this increase was not statistically significant. The net voltage dependent release of dopamine (stimulated minus basal) was similar for all groups at all time points measured. The increase in basal dopamine release in the 24 month-old animals may reflect an increased fragility or leakiness of the synaptosomal preparation. PMID- 2919004 TI - Lysosome instability in aged rat brain. AB - The study of the age-dependent change in lysosomal enzyme activities of the cerebral tissue showed the significant increase of cathepsin D in the aged rat brain, while those of beta-glucuronidase and acid phosphatase remained unchanged. The subcellular distribution study of cathepsin D and beta-glucuronidase revealed the increased activity of these enzymes in the cytosolic fraction from the aged brain. In vitro incubation of the lysosome fraction from the aged rat brain resulted in more leakage of these two enzymes, indicating the instability of the lysosome in the aged brain, which resembled the effect of L-Leu-methyl ester to the lysosome. PMID- 2919005 TI - Myorelaxant effect after intrathecal injection of antispastic drugs in rats. AB - The effects of intrathecal (i.th.) injections of antispastic drugs were studied on spontaneous activity in the electromyogram (EMG) in genetically spastic rats and on spinal reflex transmission in anaesthetized normal rats. Baclofen, 0.2-2 nmol, and midazolam, 10-80 nmol, suppressed tonic activity in the EMG recorded from the gastrocnemius muscle in mutant rats, whereas tizanidine, 1-100 nmol, enhanced it. The action of baclofen was antagonized by i.th. co-administration of delta-aminovalerate but not by bicuculline, that of midazolam by systemic pretreatment with Ro 15-1788. The effect of i.th. tizanidine was antagonized by co-administration of prazosin but not by yohimbine. Baclofen, 2 nmol, exerted suppressant effects on Hoffman (H)-reflexes and spinal flexor reflexes in normal animals, midazolam, 80 nmol, only on flexor reflexes. Tizanidine, 100 nmol, failed to suppress H-reflexes and flexor reflexes. The present results demonstrate a myorelaxant effect of i.th. injections of baclofen and midazolam but not of i.th. tizanidine. PMID- 2919006 TI - Neuritic outgrowth in primary cell culture of neurons from the squid, Loligo pealei. AB - Giant fiber lobe (GFL) cells obtained from healthy squid reliably produced neuritic processes in culture. The processes were of two types, a sheet-like veil or thin branching neurites. The latter type was often associated with bulbous expansions (presumptive growth cones), at the termini, at branch points, or at sites of apparent contact among branches from two different cells. On poly-L lysine substrate, veiling usually occurred by the fourth or fifth day in culture, while the branching processes appeared by one week to ten days. The elaboration of the outgrowths by the GFL neurons was influenced by the culture substrate and incubation temperature. The development of a preparation in which isolated GFL somata extend neurites in an easily controlled environment will permit the detailed study of axon fusion, channel expression and turnover, and synapse formation in the neurons. PMID- 2919007 TI - Myelin formation in myelin-deficient rat spinal cord following transplantation of normal fetal spinal cord. AB - Previous studies of the myelin-deficient rat spinal cord have suggested that astrocytes may play a role in preventing the formation of myelin in this mutant, or causing its breakdown. Comparison of mutant and normal littermate spinal cords shows a marked hypertrophy of astrocytes in the mutant in both gray matter and fiber tract regions. Nevertheless, when normal fetal spinal cord fragments are transplanted into mutant host spinal cord, clusters of normal-looking myelin sheaths develop with no sign of attack by host astrocytes. PMID- 2919008 TI - Identification of gamma-aminobutyric acid-like immunoreactive neurons in the rat cuneate nucleus. AB - Neurons in the cuneate nucleus of the rat were examined for gamma-aminobutyric acid-like immunoreactivity (GABA-LI) using antiserum raised against GABA glutaraldehyde-keyhole limpet hemocyanin. GABA-LI neurons were analyzed for size, shape, and distribution and compared to Nissl-stained neurons. GABA-LI cell bodies were located at all rostral-caudal levels and were distributed randomly throughout the nucleus except at the level of the obex, where they were limited to the peripheral region of the cuneate nucleus. GABA-LI cell bodies had a significantly smaller mean cross-sectional area than the total cuneate neuronal population and comprised 21.5% of the total neuronal population as assessed with Nissl-staining. These results are consistent with the hypothesis that GABA is involved in processing somatosensory information in the rat dorsal column nuclei. PMID- 2919009 TI - The rabbit retina: a suitable mammalian tissue for obtaining astroglia-free Muller cell cultures. AB - Monolayer cultures were prepared from two distinct parts of early postnatal rabbit retinae. Cell suspensions obtained from the developing medullary ray (MR) region contained neurons, Muller (glial) cells, and astrocytes, cells obtained from the remainder (peripheral) part of the retina contained neurons and Muller cells, but no astrocytes. Muller cells lack glial fibrillary acidic protein (GFAP) immunolabeling in situ but some of them acquire faint GFAP labeling in both types of cultures. Strongly GFAP-labeled cells, most likely astrocytes, were seen in MR cultures only. We propose that the periphery of the rabbit retina is ideal for obtaining astroglia-free Muller cell cultures to study their functional properties in vitro. PMID- 2919010 TI - The conditioning effect of optic nerve injury upon axonal regrowth from adult rat retinal ganglion cells explanted in vitro. AB - An in vitro assay was used to determine the effects of conditioning nerve lesions on the regeneration of adult rat retinal ganglion cell (RGC) axons from retinal explants. Following the conditioning lesion (CL) of unilateral optic nerve transection, maximal regrowth was seen from RGC explanted from ipsilateral retinae 10 days post-CL. Explants from this group initiated axonal regrowth earlier and a greater percentage regrew axons when compared with explants from normal rats. Axonal regrowth from explants of retinae contralateral to CL was also seen earlier than normal. In further experiments, the effects of both exposure of the optic nerve sheath in the orbit and the incision of the dura without injury to optic nerve axons were studied. The conditioning effect of a dural incision was found to be the same as that of optic nerve transection, whilst exposure of the optic nerve sheath had no conditioning effect on RGC axonal regrowth in vitro. PMID- 2919011 TI - Preferential adhesion of chick central neurons to the gray matter of the central nervous system. AB - Dissociated chick neocortical neurons were cultured on cryostat sections of the rat central nervous system. The neurons adhered to and grew on the gray matter of the tissue derived from various parts of the central nervous system (CNS), but were not seen on the white matter. However, cell attachment was seen on sciatic nerve. This preferred adhesion to and growth on the gray matter of the CNS was abolished by irradiation of ultraviolet light which is supposed to denaturate proteins without disturbing tissue architecture. These observations suggest that differential cell adhesion to the gray and white matter could be ascribable to localization of some adhesive molecule(s) in the gray matter or to localization of nonpermissive molecule(s) in the CNS gray matter. PMID- 2919012 TI - The re-expression of two myosin heavy chains in regenerated rat muscle spindles. AB - The vascular supply and tendons of the extensor digitorum longus (EDL) muscles of two adult rats were unilaterally severed and the muscles were allowed to regenerate for 40 days. Serial frozen sections of muscle grafts were cut and stained for enzymes that delineated fiber type, sensory endings and motor endings. MF30 and ALD58, two antibodies which react only to intrafusal fibers in normal rat muscle, were reacted against sections of nerve-intact muscle grafts. Data were compared to that from muscles of normal rats. Encapsulated fibers devoid of sensory innervation and some extrafusal fibers in muscle grafts had a weak to moderate reaction to MF30, but no reaction to ALD58. Regenerated, encapsulated fibers with sensory innervation bound both MF30 and ALD58. These data indicate that afferents which reinnervate regenerated spindles retain the capacity to induce expression of spindle-specific myosin isoforms in rats. PMID- 2919013 TI - Is a retinal input involved in the generation of eye resetting fast phases in the frog eye optokinetic nystagmus? AB - An intravitreal injection of cis-2,3-piperidine dicarboxylic acid (PDA), a glutamate analog, in one eye only, decreased or even totally suppressed the eye resetting fast phases (ERFPs) of the frog optokinetic nystagmus (OKN) in monocular as in binocular situations. On the opposite, for low drum speeds, the slow phase eye velocity was not affected by PDA. Moreover, it seems that intravitreally injected PDA does not act upon central structures responsible for OKN. Our experiments suggest that a retinal input may be involved in triggering the ERFPs in the OKN. PMID- 2919014 TI - The ability of gustatory stimuli to modify the cardiac sympathetic and vagus nerve activities. AB - The effects of chemical stimulation of the oro-lingual mucosa on the heart rate and arterial blood pressure were studied together with changes in the cardiac nerve activities in the rat. Of four qualities of basic taste stimuli, only HCl and NaCl but not quinine and sucrose were effective in increasing the heart rate and blood pressure. These changes in the cardiovascular system were associated with an increase in the efferent cardiac sympathetic activity and a decrease in the vagal activity, although they were no longer appreciable after transection of the glossopharyngeal nerve. PMID- 2919015 TI - Correlation between intracellular pH and lactate levels in the rat brain during potassium cyanide induced metabolism blockade: a combined 31P-1H in vivo nuclear magnetic spectroscopy study. AB - Female Sprague-Dawley rats were chronically implanted with nuclear magnetic resonance (NMR) surface coils tuned to both 31P and 1H NMR frequencies. Alternated 31P and 1H NMR spectra were recorded at 2.5 min intervals in waking rats or rats under pentobarbital or chloral hydrate anesthesia. After a reference period, the metabolic changes were observed following intraperitoneal injection of potassium cyanide (KCN, 5 mg/kg). Among previously observed changes typical of cellular anoxia, attention was specifically paid to the relationship between the intracellular pH values and the lactate levels. The results show a strong lactate pH correlation in waking rats, a partial decoupling under nembutal anesthesia and a complete decoupling under chloral hydrate anesthesia. PMID- 2919016 TI - Meningococcal vaccine--do some children experience side effects? AB - In order to stop an outbreak of group A meningococcal meningitis, 130,000 Auckland children were immunised. During the month following vaccination there were 546 reports of unusual clinical events reported by parents and practitioners, together with 40 specialist paediatric assessments of children presenting with neurological symptoms. In 25 of these latter there was complete agreement between the history as presented by parents in the initial telephone report and the paediatrician's subsequent summarised history. Of the 546 reports, 217 either had too little detail for an assessment or the symptoms were clearly attributable to other causes. Of the remaining reports, there were 152 cases of fever with or without other symptoms; 85 were of rash and local reactions within 24h of vaccination; 63 reports were of headache, stiff neck and myalgia within 48h of vaccination. There were 92 reports of apparent peripheral nerve involvement, including 80 reports of unexplained weakness and 57 reports of paraesthesia or dysaesthesia. Both motor and sensory symptoms occurred in some children; none were permanent. The effects of adverse publicity during the campaign on the genesis of some symptoms is acknowledged, but the possibility that short term neurological symptoms occur after vaccination seems likely and has not been previously reported. PMID- 2919017 TI - Life after Cartwright. PMID- 2919018 TI - Treatment of premenstrual symptoms in Wellington women. AB - A survey of 1826 women in the Wellington region was carried out. Participants were asked about their general and gynaecological health, as well as detailed questions about their last menstrual cycle. The majority (1456) had had a menstrual period within the last month or so. Eighty five percent of these women noted premenstrual symptoms of some kind, and were asked about a variety of self help measures, and medical help, for these, and whether the advice and/or treatment was in fact helpful. Nine hundred and ninety women had tried self-help while four hundred and sixteen had sought medical help. The most commonly tried self-help measures were exercise, rest and vitamin B6. Half the women had tried each of these. Overall, there was a marked placebo response, but exercise, rest and keeping a written diary of symptoms were all helpful in over eighty percent of those who tried them. Doctors offered a wide range of treatments, including vitamin B6, diuretics, oral contraceptives and mefanamic acid, but the effect of these was difficult to evaluate further. When the sample was subdivided into clusters of women who shared similar symptoms, significant differences in the effectiveness of different self help measures emerged. Four different premenstrual syndromes are suggested: PMS-breast, PMS-bloat, PMS-irritable and intolerant, and PMS-various. PMID- 2919019 TI - Children admitted to a general intensive care unit. AB - A retrospective analysis of the pattern of admission of children to the general intensive care unit of Christchurch Hospital during the period 1980-7 inclusive, is reported. Three hundred and ninety-nine children were admitted during this period and they formed 10.7% of all admissions to the unit. In addition to the intensive care specialist, a paediatrician was involved with the management on 260 occasions and a surgeon on 139 occasions. Acute epiglottitis was the single commonest medical cause for admission and trauma from motor vehicle accidents the commonest surgical reason. Overall mortality was 14.5%, 13% for medical conditions and 16% for those with surgical problems. These results are in keeping with those reported from overseas. PMID- 2919021 TI - How safe is anaesthesia in New Zealand? PMID- 2919020 TI - Psychobiological effects of gastric restriction surgery for morbid obesity. AB - A sample of 36 patients who had undergone gastric reduction surgery for severe obesity was seen postoperatively and psychobiological changes assessed. Subjects reported substantial weight losses with reduced food intake and normalisation of eating habits. In the majority of patients positive changes had occurred in attitudes and improvements were found in mood, social and sexual functioning. Low rates of psychological disturbance were reported. PMID- 2919022 TI - AIDS and the health care worker. PMID- 2919023 TI - Autopsy and the cause of death. PMID- 2919024 TI - Contraceptive practice in New Zealand. PMID- 2919025 TI - Diet and heart disease. PMID- 2919026 TI - High-dose inhaled corticosteroids. PMID- 2919027 TI - O & G textbooks revised. PMID- 2919028 TI - Changes in dose limitation. PMID- 2919029 TI - Use of sodium iodide to overcome the eluate age restriction for Ceretec reconstitution. AB - The Ceretec kit for preparation of 99Tcm-hexamethylpropyleneamine oxime (HMPAO) complex for the investigation of regional cerebral blood flow requires careful handling by the radiopharmacist and a number of restrictions have been placed on the kit relating to the nature of 99Tcm generator eluate used for reconstitution. The addition of sodium iodide to eluate immediately after elution can remove one of these restrictions. A level of 0.4 mg sodium iodide added after elution allows reconstitution of Ceretec up to 6 h later with no adverse effect on radiochemical purity. This offers a simple method for the use of this product if availability of fresh technetium generator eluate is a constraint. PMID- 2919030 TI - The evaluation of right ventricular function in acute myocardial infarction by xenon-133. AB - Right ventricular performance was assessed in 37 patients with acute myocardial infarction within two hours of admission to Coronary Care and compared to results in 21 normal volunteers and 12 patients undergoing coronary arteriography. Right ventricular ejection fraction (RVEF) was measured from gated xenon-133 scans. The normal range of RVEF (42.8 +/- 5.1%) was significantly higher than in the 30 patients with inferior infarction (26.3 +/- 10.9%; p less than 0.001) and was similar to that in patients with anterior infarct (40.6 +/- 5.4%; ns) and patients undergoing coronary arteriography (39.3 +/- 4.9%; ns). Fifteen of the patients with inferior infarct had clinical evidence of right ventricular dysfunction with a mean RVEF of 18.9 +/- 7.9%, significantly below the fifteen patients with no clinical evidence of right ventricular dysfunction (34.3 +/- 8.3%; p less than 0.001). PMID- 2919031 TI - The effect of eating on transit through the small intestine. AB - The effect of eating on the transit of radiolabelled particles through the small intestine has been monitored in eight healthy subjects dosed after an overnight fast. Each subject participated on three occasions and either remained fasting for 9 h after dosing or consumed a meal at 1.5 h or 4 h. The mean +/- 1 S.D. small intestinal transit time during the fasting study was 5.5 +/- 2.1 h and during the 1.5h and 4 h fed studies 4.8 +/- 2.9 h and 4.7 +/- 2.2 h, respectively. These times were not significantly different, nor were the rates of entry of the particles into the colon. These findings indicate that once in the small intestine the efficacy of orally administered pharmaceutical preparations is unlikely to be affected by eating. PMID- 2919032 TI - Diagnostic potential of diuresis renography: limitations by the severity of hydronephrosis and by impairment of renal function. AB - Eighty ureterorenal units (65 patients) with upper urinary tract dilatation underwent pressure perfusion studies and diuresis renographies separated by short intervals. Pressure perfusion studies were evaluated as suggested by Whitaker, while wash-out curves of diuretic renographies were analysed quantitatively by calculating peak elimination rates. Upper urinary tract volume was estimated from i.v. urographies and measured directly in 21 cases. Renal function was assessed from base-line renograms and plasma creatinine levels. In patients with minor upper urinary tract dilatation (less than 30 ml) the two procedures agreed in 88% of cases, in those with massive dilatation (greater than 70 ml) agreement was limited to 58%. Diuretic renal scans were more often obstructed than pressure perfusion studies in the latter situation. The effect of severely reduced renal function was less prominent than that of massive dilatation. This was confirmed by the exaggerated response to frusemide reflected by urinary flow measurements in patients with a creatinine clearance of 10 ml min-1 or less. Of the eight patients with severely reduced renal function, who did not show full agreement between the procedures, six had massive dilatation of the upper urinary tract. PMID- 2919033 TI - Bilateral compressive optic neuropathy secondary to bilateral sphenoethmoidal mucoceles. AB - We have presented a rare case of bilateral posterior sphenoethmoidal sinus mucoceles with bilateral compressive optic neuropathy. While the duration of compression was variably present over a 10-month period, there were nevertheless significant improvements in visual acuity of the right eye and visual fields bilaterally following extensive optic nerve decompression. PMID- 2919034 TI - Fusarium oxysporum keratitis. AB - We describe herein a patient with a rare occurrence of mycotic keratitis caused by Fusarium oxysporum. The fungus destroyed the cornea, and a perforating corneal graft had to be performed. The drug of choice in such diagnosed cases is natamycin. A comparison between Fusarium oxysporum and Fusarium solani is discussed. PMID- 2919035 TI - Cytology of intraocular lens surface: a transmission electron-microscopic study. Cytology of intraocular lens surface. AB - We developed a new method for specimen preparation for transmission electronmicroscopic study of cellular responses on intraocular lenses. This procedure omits propylene oxide treatment of the materials to be studied, which is normally a step in the routine preparation process for transmission electron microscopy. It was previously found that propylene oxide treatment dissolves intraocular lenses. Using our procedure, two types of cells were identified on intraocular lenses removed from monkey eyes 7 days after implantation. These cells had the typical structural features of multinucleated giant cells and of macrophages. It thus appears that this procedure will permit study of the cytology of intraocular lens surfaces. PMID- 2919036 TI - Study of a new series of large relaxing retinotomies. AB - Silicone oil injection followed by retinotomy was performed in a second series of 37 patients with retinal detachment and advanced proliferative vitreoretinopathy. The retina posteriorly to the retinotomy was attached in 16 eyes with at least 18 months of follow-up. Ambulatory vision or better vision was restored in 12 eyes. The size and the site of the retinotomy depend on the size and the site of the retraction. PMID- 2919037 TI - Neuroretinal rim area in normal eyes: a study on a randomized group of 30 subjects. AB - This study was undertaken in order to evaluate the range of the neuroretinal rim area in a normal sample and the repeatability of manual photogrammetric measurements. Thirty randomly chosen eyes from 30 subjects without ocular disease were examined: the mean disc area (2.20 +/- SD 0.58 mm2), the mean cup area (0.36 +/- 0.29 mm2) and the mean rim area (1.83 +/- 0.37 mm2) were evaluated. All the measurements were performed by two independent observers and were corrected to the actual size by measuring refraction and axial length of each eye. A linear correlation among disc areas (r = 0.71), cup areas (r = 0.93) and rim areas (r = 0.74) between the two observers was found. Furthermore, a highly significant correlation between disc area and rim area was observed (r = 0.90) together with a correlation between the disc and cup area (r = 0.82). A correlation between disc area and axial length was finally found (r = 0.59). The neuroretinal rim area has been expressed as a percentage of the total disc area. Percent values (+/- SD) were clustered around a mean of 84.83 +/- 8.8%. Despite their high degree of repeatability, our data are slightly different from those previously reported by other authors. PMID- 2919038 TI - Accuracy of memory-guided saccades. AB - Accuracy of saccades toward a remembered target positions in the dark (memory guided saccades) was studied in 11 normal subjects. The subjects were instructed to execute saccades with amplitudes of 20, 40, 60, and 80 degrees, centering on the primary position. Saccades were initially performed for 30 s with visual fixation targets. The targets were then switched off. The subjects continued saccades in the dark with the given amplitude. Most memory-guided saccades overshot the target. Saccades with an amplitude error of 12.7 +/- 7.3 degrees (mean +/- SD) were followed by corrective saccades, while no corrective saccades occurred following saccades with an error of 4.3 +/- 4.0 degrees. The accuracy of initial memory-guided saccades decreased with time. However, the amplitude of the memory-guided saccades was corrected when the error was beyond about 5 degrees. These results suggest that memory-guided saccades are not repetitions of visually guided saccades, but nonvisual error signals relate to the control of eye movements in the dark. PMID- 2919039 TI - Bilateral macular coloboma associated with progressive atrophy of the peripheral retina. AB - An 11-year-old girl with poor visual acuity since birth was found to have nearly complete defects of the retinochoroidal tissue in the central areas of both fundi and almost normal peripheral retinas. Her parents were first cousins. At age 24, the patient reported night blindness. An examination showed geographic atrophy of the peripheral retina and stationary macular lesions in both eyes. Her condition appeared to be a rare case of bilateral macular coloboma associated with progressive peripheral retinal atrophy. PMID- 2919040 TI - Controlling risks of the possible transmission of human immunodeficiency virus. Notice of American Academy of Ophthalmology Clinical Alert 2/4. PMID- 2919041 TI - Increased scleral rigidity and age-related macular degeneration. AB - The coefficient of scleral rigidity of the eyes of 29 patients with age-related macular degeneration (ARMD) was significantly higher than the rigidity of 25 control patients, frequency matched for age. The data suggest that an increased scleral rigidity may be a significant risk factor for the development of the disorder. PMID- 2919042 TI - Improved reading performance using individualized compensation filters for observers with losses in central vision. AB - By boosting the amplitudes of the intermediate spatial frequencies more than the amplitude of the lower spatial frequencies, reading performance improved significantly when observers with losses in central vision read words that were filtered. Words that were filtered using an image enhancement function based on an observer's losses in visual function relative to a normal observer (1) reduced the magnification (30-70% less magnification was needed) and (2) increased the reading rate (2-3 times), measured in words per minute. The greater the loss in central visual function, the more individualized compensation filters reduced the magnification needed for word recognition. Individualized compensation filters improved the clarity and visibility of words for low vision observers. This study also found that the shape of the enhancement function was important to determine the optimum compensation filter for improving reading performance. In addition, the individualized compensation filters can be implemented by inexpensive hardware, for example in a closed circuit television (CCTV), to provide a significantly more effective low vision aid for observers with losses in central vision to read text, than is provided using only magnification. PMID- 2919043 TI - A comparison of the blue color mechanism in high- and low-tension glaucoma. AB - Twenty-five eyes of 25 high-tension glaucoma patients and 25 eyes of 25 low tension glaucoma patients matched for similar visual field defects had their spectral increment threshold measured. Patients with high-tension glaucoma showed significant losses in both chromatic and achromatic sensitivities when compared with low-tension glaucoma patients. The results support the hypothesis that there may be different mechanisms of damage in glaucoma. PMID- 2919044 TI - Errors in the three-step test in the diagnosis of vertical strabismus. AB - The Parks three-step test is the standard for diagnosing which isolated cyclovertical muscle is palsied. It does not, however, tell the examiner if in fact one is dealing with a palsy of one cyclovertical muscle. Numerous other causes of vertical strabismus may have a positive Bielschowsky head tilt test. The use of the three-step test in these clinical situations may lead to incorrect diagnosis and treatment. These clinical conditions include contracture of the vertical recti, paresis of more than one vertical muscle, dissociated vertical divergence, previous vertical muscle surgery, skew deviation, myasthenia gravis, and small nonparalytic vertical deviations associated with horizontal strabismus. Several diagnostic steps in addition to the three-step test are necessary to tell if one is in fact dealing with a palsy of a single cyclovertical muscle. PMID- 2919045 TI - Strabismus in infancy. AB - In order to prospectively study the development of strabismus in infancy, the ocular alignment of a large population of normal neonates was studied and follow up examinations were obtained in a subset of these infants. The characteristic findings of congenital esotropia subsequently developed in three infants who were either orthotropic or exotropic at birth. Pathologic exotropia developed in two infants; both were exotropic at birth, but no more so than most normal neonates. In infants with congenital esotropia or pathologic exotropia, the characteristic deviation appears to develop between 2 and 4 months of age, a period during which normal infants are becoming increasingly orthotropic. PMID- 2919046 TI - Cyclophotocoagulation: how far posterior to the limbus is the ciliary body? PMID- 2919047 TI - Peripapillary crescents and halos in normal-tension glaucoma and ocular hypertension. AB - In normal-tension glaucoma ("low-tension" glaucoma), 21 of 33 eyes (64%) had a peripapillary chorioscleral crescent or halo, compared with 13 of 38 eyes (34%) with ocular hypertension. The average area of bared choroid and sclera was greater in normal-tension glaucoma (5.8 arbitrary units of area) than in ocular hypertension (1.4 units). Myopic eyes were prevalent among the normal-tension glaucoma group. When eyes with more than 4 diopters (D) of myopia were excluded from the analysis, the difference in prevalence and size of chorioscleral crescents and halos remained. Thus, the presence of a crescent correlates with disc damage, but further work is needed to determine if the correlation represents peripapillary atrophy that accompanies glaucomatous nerve atrophy or represents a greater susceptibility of discs with preexisting peripapillary abnormality. PMID- 2919048 TI - Clinical histologic correlation of human peripapillary anatomy. AB - The various types of peripapillary crescents which are observed clinically are generally interpreted to represent misalignments of the edges of the neural retina, retinal pigment epithelium (RPE), choroid, and sclera at the disc margin. In order to test the validity of conventional assumptions about the anatomic basis for each type of crescent, the authors compared histologic sections to previously obtained clinical photographs and fluorescein angiograms of 21 eyes enucleated for choroidal melanomas. The authors' results define several configurations of peripapillary tissue, but also show that there can be more than one anatomic basis for some appearances. A scleral lip, which consists of an anterior extension of sclera to separate the choroid from the optic nerve head, is nearly always present, and ophthalmoscopically appears as a white rim that marks the disc margin and accumulates fluorescein after the vascular transit in an angiogram. A chorioscleral crescent occurs when the RPE is retracted from the disc margin, most prominent when associated with a tilted exit canal for the axon bundles through the sclera. In such a crescent, the choroid may be thinned or absent next to the disc, exposing to view some of the underlying sclera. Malposition of the embryonic fold occurs when the boundary between the neural retina and the RPE does not coincide with the embryologically formed fold in the neuroectoderm that occurs at the disc. When this occurs, there is either a double layer RPE (forming a very dark pigment crescent) or a double layer of incompletely formed neural retina adjacent to the disc.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2919049 TI - The effect of age on normal human optic nerve fiber number and diameter. AB - In one optic nerve from each of 19 persons, the authors determined the number of axons, the distribution of fiber diameter, and the total neural area. The mean fiber count was 693,316, the mean neural area was 5.17 mm2, and the mean axonal fiber diameter was 0.96 microns. No significant decline in fiber number or neural area with increasing age was found. The authors found a large variability of axonal number among their patients. This variability would have obscured any small effect of aging. Linear regression analysis of the effect of age on mean axonal diameter yielded a slight negative slope (P less than 0.01), suggesting a redistribution of fiber diameter. This could occur from axonal shrinkage, from preferential large fiber loss, or from the technical features of tissue acquisition and analysis. The authors suspect that the explanation is a selective loss of large nerve fibers. PMID- 2919050 TI - Corneal topographic changes after radial keratotomy. AB - A high resolution photokeratoscope using digital video image acquisition and computer graphics was used to describe anterior corneal topography before and after radial keratotomy. After radial keratotomy, the entire cornea is flattened, but this effect is more pronounced centrally. The flat central "optical zone" varies in size, shape, and location. Regional variations in corneal power may explain phenomena observed after radial keratotomy, such as visual acuity that is better than would be expected on the basis of refractive error, and the occurrence of ghost images. PMID- 2919051 TI - The fellow eye of patients with phakic lattice retinal detachment. AB - A retrospective study was performed to determine whether the prophylactic treatment of areas of lattice degeneration, holes, or breaks reduced the risk of subsequent new breaks or detachment in the fellow undetached phakic eyes of patients with a phakic lattice retinal detachment (RD). Three hundred eighty eight consecutive patients who presented to the University of Iowa between 1959 and 1984 were followed for a mean of 7.9 +/- 5.8 years after the detachment in the first eye. Fellow eyes which received no prophylactic treatment had a 2.5 times greater risk of a new break or RD over 7 years than eyes receiving full prophylactic treatment (19.4 versus 7.5%; P = 0.0002). Fellow eyes receiving no treatment also had a greater risk of a new RD over 7 years than eyes receiving full treatment (5.1 versus 1.8%; P = 0.0125). These results do not allow us to make recommendations concerning which fellow eyes, if any, should be prophylactically treated. On the one hand, prophylactic treatment did significantly reduce the risk of new breaks and detachments. On the other hand, however, prophylactic treatment reduced the risk of new RD alone in the fellow eye only from 5.1 to 1.8% over 7 years. In addition, prophylactic treatment did not reduce the risk of detachment in the higher risk eyes with high myopia or extensive lattice. PMID- 2919052 TI - Image analysis of fundus photographs. The detection and measurement of exudates associated with diabetic retinopathy. AB - A computer-based image analysis system was used to detect and measure exudates in fundus photographs. A fundus transparency was imaged, digitized, and stored in image memory. The stored image was then processed by several operators, to reduce shade variations in the image background and enhance the contrast between this background and the exudates. Exudates were separated from the background on the basis of their brightness or "gray level" and were then copied in to a binary image. For comparative purposes, the binary image was superimposed on the original unprocessed image. Exudate areas were measured using the binary image, which was also transferred to a printer to provide a permanent record or "exudate map." The system was able to discriminate between standard photographs used to grade hard exudates in the Early Treatment for Diabetic Retinopathy Study (ETDRS). It was also used to monitor the response of a subject to laser treatment. PMID- 2919053 TI - Atrophic creep of the retinal pigment epithelium after focal macular photocoagulation. AB - To determine if enlargement of laser scars occurs in nonmyopic individuals, the authors retrospectively reviewed 126 consecutive patients with age-related macular degeneration who had been successfully treated with focal macular laser photocoagulation for subretinal neovascularization. Of the 174 laser scars in the study, 122 (70%) increased in size from 50 to 1016 microns (mean, 290 microns) as determined photographically on serial examination ranging from 2 to 81 months. There was no statistically significant difference in the number of scars which increased in size among the three laser wavelengths used. Four (3%) patients lost vision as a result of the scar extending into the fovea. Enlargement of retinal pigment epithelial (RPE) atrophy after focal macular laser photocoagulation may cause significant, delayed visual loss after successful treatment of subretinal neovascularization. PMID- 2919054 TI - Infrared thermography in oral and maxillofacial surgery. AB - A highly sensitive infrared thermographic camera was evaluated in a variety of physiologic and pathologic conditions associated with the head and neck. Although it may have clinical applications, particularly in the field of facial pain and the temporomandibular joint, such wide variations in normal values were noted that any standardization was extremely difficult. PMID- 2919055 TI - A study of the utility of measuring mandibular mobility by means of the interincisal dimension. AB - The purpose of this investigation was to determine the reliability of using the interincisal dimension as a measure of mandibular range of motion. Thirty patients who underwent mandibular advancement and 15 patients who underwent mandibular setback were included in this study. Preoperatively, a lateral cephalogram in centric relation and a second cephalogram with the mandible at maximum voluntary gape were obtained. Immediately following surgery, another centric relation cephalogram was obtained. A composite tracing of the two preoperative tracings was made to show how the mandible changed in position from the closed-mouth to the open-mouth radiographs. The proximal segment (ramus) of the postoperative cephalogram was then superimposed on the open-mouth mandibular ramus, and the distal segment of the postoperative mandible was drawn. This composite produced a tracing of what the postoperative maximal gape cephalogram would be if the same amount of condylar rotation and translation as in the preoperative tracing had occurred. The preoperative interincisal dimension was recorded on the composite tracings (factoring in any overbite or openbite) as was the would-be postoperative interincisal dimension. These measures were compared using the paired t test and Pearson's correlations to determine if there were any significant differences between them. The results showed that the interincisal dimension is a fairly reliable measure of mandibular mobility even when the length of the mandible is altered with surgery. PMID- 2919056 TI - Thromboembolic risk factors in patients undergoing maxillofacial surgery for malignancies. AB - Venous thromboembolism is a common complication in patients undergoing major surgery. We studied blood coagulation profiles in 16 patients undergoing extensive maxillofacial surgery for oral malignant diseases. Activity of coagulation factor V and levels of antithrombin III were significantly reduced on the first postoperative day. Fibrinogen level showed a continuous increase throughout the observation period. However, no thromboembolic events were observed. It can be concluded that despite a severe alteration of the blood clotting system, maxillofacial surgery does not seem to be associated with postoperative thromboembolism. PMID- 2919057 TI - Bilateral hyperplasia of the mandibular coronoid processes: a report of two cases. AB - Two cases of bilateral coronoid hyperplasia of the mandible are presented. Consistent with other reported cases, the patients were men whose onset of symptoms correlated with the onset of puberty. One case was unusual in that bilateral coronoidectomies did not relieve the restriction of mandibular movement. Additional masseter muscle and fascial surgery was required to provide unrestricted mandibular motion. PMID- 2919058 TI - Xeroradiography in the diagnosis of nonradiopaque sialoliths. AB - Sialolithiasis may be the most common disease of the salivary glands in patients more than 20 years of age. Approximately 19% of sialoliths occur in the parotid gland. Of these, only up to 71% can be successfully diagnosed radiographically. The remaining 29% provide a diagnostic dilemma. Xeroradiography, because of its tissue-edge enhancement, can distinguish tissue margins of different density more dramatically than can conventional imaging and is an invaluable aid in the diagnosis of nonradiopaque sialoliths. PMID- 2919060 TI - Metastatic adenocarcinoma of the colon presenting as periradicular periodontal disease: a case report. AB - Metastases to the jaws account for only 1% of all malignant tumors of the oral cavity. Consequently the diagnosis of metastasis to the mandible requires a high degree of clinical suspicion and the use of a systematic diagnostic approach. In this case report a patient sought treatment for what appeared clinically and radiographically as periradicular periodontal disease. However, because the patient had a medical history of adenocarcinoma of the colon 5 years previously, metastasis to the jaws was included in the differential diagnosis. Metastasis to the jaws may resemble periodontal disease or many of the other benign and malignant conditions that affect the jaws, thus making the correct radiographic diagnosis difficult. Ultimately, histologic evaluation is essential to make a definitive diagnosis. PMID- 2919059 TI - Effect of chlorhexidine rinsing on the oropharyngeal ecology in patients with head and neck cancer who have irradiation mucositis. AB - Oral flora is thought to contribute to irradiation mucositis in patients with head and neck cancer. Neglect of oral hygienic care may also contribute to mucositis. The purpose of this prospective, randomized, placebo-controlled, double-blind study was to evaluate the effect of chlorhexidine 0.1% mouthrinses on oral flora and irradiation mucositis. This study included 30 patients with head and neck cancer who had comparable irradiation portals. One group (N = 15) rinsed four times daily with chlorhexidine 0.1%, the other group (N = 15) with a placebo. The oral flora was cultured (oral washing technique) twice before and three times per week during the period of radiotherapy. On the same days, the severity of mucositis was determined. The colonization index of viridans streptococci was significantly reduced only after 5 weeks of chlorhexidine 0.1% treatment. The colonization patterns of Candida species, Streptococcus faecalis, staphylococci, and Enterobacteriaceae, Pseudomonadaceae, and Acinetobacter species were not influenced by 5 weeks of use of chlorhexidine rinses when compared with the placebo. No differences were seen between the two study groups in the development and severity of mucositis. In conclusion, suppression of oral flora and a lowering of the severity of mucositis by means of disinfecting mouthrinses were not successful. PMID- 2919061 TI - Odontomas. AB - A total of 351 odontomas were retrieved and analyzed from 53,824 submitted specimens. The majority (53.6%) were diagnosed in the second decade of life; the most common location was the anterior portion of the maxilla (33.9%), but there was no overall predilection for the maxilla. An associated unerupted tooth was present in at least 47.6% of the cases. Dentigerous cysts were diagnosed in conjunction with 27.6% of the odontomas, and a calcifying and keratinizing odontogenic cyst was seen in 0.9% of the cases. PMID- 2919062 TI - Epidermoid cyst of the buccal mucosa. AB - An uncommon case of a large epidermoid cyst arising within the buccal mucosa is described. PMID- 2919063 TI - Crossed congenital hemifacial hyperplasia. AB - Crossed congenital hemifacial hyperplasia is a rare condition that produces facial asymmetry and overgrowth of the opposite lower extremity. A case involving the left side of the head and the right foot is presented. Etiologic theories are discussed. The involvement of crossed structures suggests the possibility that the cause may be related to abnormalities of the nervous system. PMID- 2919064 TI - Monoclonal antibodies to HSV-infection-related antigens cross-react with tumor cell lines and tumor tissue sections. PMID- 2919065 TI - A new root canal instrument and instrumentation technique: a preliminary report. AB - Cleaning and shaping the root canal system has been and continues to be a challenge for even the most experienced endodontist. Curved, narrow canals, in particular, cause difficulties for the beginner as well as the specialist. A new instrument designed to incorporate new concepts was developed to ameliorate the problems in cleaning and shaping root canal systems. This new instrument has been given the name of SW (Senia and Wildey). The new SW instrument uses controlled right and left rotational forces. This motion was used to clean and shape simulated root canals in plastic blocks and root canals in extracted teeth. Instrumentation appeared to be easier, faster, and more precise than with conventional instruments, especially in curved canals where there was remarkable reduction of canal transportation. A mechanical version of the SW instrument was also developed. It was used to flare the coronal portion of the root canal system. PMID- 2919066 TI - Multiple idiopathic root resorption: diagnostic considerations. AB - Multiple idiopathic root resorption is a specific entity that must be delineated from all other resorptive processes. We present a case report and discuss the diagnostic possibilities that must be considered before arrival at this diagnosis. PMID- 2919067 TI - The application of panoramic zonography to the diagnosis of maxillofacial fractures. AB - Traditionally, multiple radiographic views and techniques were required to elucidate the nature and extent of fractures of the maxillofacial complex. As a result, patient cost in terms of time, expense, manipulation, and radiation exposure scaled upward. Synthesis and interpretation of the fragmented bits of information from multiple films also constituted a labor-intensive process. A new imaging modality, panoramic zonography, provides precise anatomic imaging of preselected areas of interest with minimal radiation exposure. The usefulness of this technique in the diagnosis, treatment, and follow-up of traumatic events in the mandibular and maxillofacial regions is illustrated by a series of cases. PMID- 2919068 TI - The effects of temporomandibular joint internal derangement and degenerative joint disease on tomographic and arthrotomographic images. AB - In a blind study, 243 arthrograms were interpreted as showing normal disk position, anterior disk displacement with reduction, or anterior disk displacement without reduction. The presence or absence of a perforation of the posterior attachment or disk was recorded. Later, tomograms of the same patient were interpreted. The presence or absence of evidence of temporomandibular degenerative joint disease (TMDJD) was recorded. The condyle-to-fossa relationship was characterized as retropositioned or not retropositioned. O the 106 cases with tomographic evidence of TMDJD, 100 (94%) had arthrographic evidence of internal derangement (p less than 0.0001), whereas 47% of the cases with internal derangement (211) had evidence of TMDJD. Perforations were seen in 29 (27%) of the cases with degenerative joint disease and in none (0%) of the cases without TMDJD (p less than 0.001). In cases without TMDJD, 90% of the cases with internal derangement revealed condylar retropositioning (p less than 0.0001). With tomographic evidence of TMDJD present, the relationship between condylar position and disk position was not significant. PMID- 2919069 TI - Evaluation of aluminum-yttrium filtration for intraoral radiography. AB - In comparison with the use of traditional aluminum filtration, a radiation dose reduction of 40% at 90 kVp and 25% at 70 kVp was found with the use of aluminum yttrium (Al-Y) filtration for intraoral bitewing and periapical radiographs. An increased exposure time, and consequent greater tube loading, was necessary to maintain film density. Extended gray-scales (i.e., reduced radiographic contrast) occurred at both energy levels tested with the use of Al-Y filtration. Subjective evaluation of image quality in terms of clarity, resolution, and contrast was carried out independently by nine periodontologists. Despite some interoperator variance, there was a preponderant preference for traditional aluminum filtration. PMID- 2919070 TI - Foreign body. PMID- 2919071 TI - Fracture of the sella turcica. PMID- 2919072 TI - Ghost foreign body. PMID- 2919073 TI - Threaded Steinmann pin embedded in the glenoid fossa. PMID- 2919074 TI - Surgical reconstruction of the arthritic knee I. PMID- 2919075 TI - Clinical results of Whiteside Ortholoc total knee replacement. AB - Three hundred and four consecutive cementless Ortholoc I TKAs were followed for 2 to 5 years. One patient had femoral and tibial component loosening. There were no cases of patellar component loosening, but six knees had failure of the patellar polyethylene surface due to wear. A major design change of the metal-polyethylene locking mechanism was effected to address this problem. The patellar component is now countersunk and the central post has been reduced in size. 79.1 per cent of the knees were graded excellent, 13.4 per cent good, 5.8 per cent fair, and 1.7 per cent poor. The Ortholoc I group was compared to a similar group of 424 Ortholoc II knees at 1 year postoperatively for pain relief. The Ortholoc II knee differs from the Ortholoc I primarily in tibial component fixation, using four peripheral 6.5-mm screws. The Ortholoc II group had significantly fewer painful knees, which suggests that the screws in the tibial component were effective in improving fixation and controlling load distribution. Survival analysis showed no tendency for the results to deteriorate over the time span studied. Cementless fixation of all components, including the tibia and patella, was highly successful and can be achieved without stress relief of the distal femur. PMID- 2919076 TI - Requirements for successful total knee replacements. Design considerations. AB - Historical review up to 1969 showed the emergence of conservative hemiarthroplasty resurfacings and rigid all-metal hinges. The first cemented metal-on-plastic design, introduced in 1969, began a decade in which a large number of different condylar designs were introduced. Variations of these condylar replacements in terms of femoral-tibial surface conformity, the fixation elements, and the provision for the patellofemoral joint produced wide variations of clinical results. In parallel with these condylar replacement designs, unicompartmental and both lax and fixed hinges were still used for particular indications. A review of all of the different design types showed that the most successful results were obtained with partially conforming condylar replacements with provision for the patellofemoral joint. Although cemented condylar replacement components composed the majority of the clinical reports, press-fit uncemented designs also had significant promise. The results of unicompartmental designs depended dramatically upon the indications. Present hinged replacements, whether lax or fixed-axis, produced problems that were sufficiently serious to restrict their use to cases in which condylar replacements were distinctly inadequate. Despite the success of condylar replacements at up to 10 years follow up, a number of problems remain. These include optimizing the femoral-tibial geometry for maximum range of motion, minimum loosening, and minimum wear. Longer term problems include improved design for long-term fixation and reduction of wear of polyethylene by optimum surface geometry, by better material quality control, or by improved materials. Whichever instrumentation system was used, surgical parameters such as component placement and sizing were shown to affect the potential range of motion. Considerations of design were given for revision cases in which condylar replacements were inadequate. Certain design suggestions were made for minimizing the serious problems used with lax or fixed-axis hinged replacements. PMID- 2919077 TI - The surgical technique for performing a total knee replacement arthroplasty. PMID- 2919078 TI - Intraoperative controls for bacterial contamination during total knee replacement. AB - The increasing number of infected total knee replacements produces a financial and social burden upon patients, families, hospitals, insurance companies, and government. Methods of reducing the problem of wound infection are discussed in this article, including prophylactic anticoagulation, CPM, autologous blood replacement, good nutrition, and careful wound closure. PMID- 2919079 TI - Postoperative care of the total knee patient. AB - After total knee surgery the three most important problems are thromboembolic disease, disorders of wound healing, and inadequate range of motion. With the use of prophylactic anticoagulation, CPM, autologous blood replacement, good nutrition, and careful wound closure, most patients will have an uneventful postoperative course and reach the maximum potential from their knee arthroplasty. PMID- 2919080 TI - Effect of posterior cruciate sacrifice on durability of the cement-bone interface. A nine-year survivorship study of 100 total condylar knee arthroplasties. AB - This article presents a survivorship analysis of the second conservative 100 primary total-condylar knee arthroplasties in 75 patients performed between 1979 and 1980, with a maximum follow-up of 9 years. With this type of knee arthroplasty, the posterior cruciate ligament is routinely sacrificed. Survivorship results revealed that 98.9 per cent of the knees had good outcome at 9 years of follow-up, using revision surgery for aseptic and septic loosening and radiographic evidence of global radiolucency or shift of the component as endpoint. Radiographic survivorship analysis showed well-fixed components in 87 per cent of implants, using endpoint criteria of appearance and progression of radiolucency under tibial component. Sacrificing the posterior cruciate ligament does not adversely affect durability of fixation of the total-condylar knee arthroplasty. Bone cement provides an excellent fixation of total knee implant. PMID- 2919081 TI - The posterior stabilized knee prosthesis. AB - The posterior stabilized knee prosthesis is a versatile and durable prosthesis with an excellent clinical record. It was designed to increase range of motion, improve stair climbing, and prevent posterior tibial subluxation. PMID- 2919082 TI - Is kinematic total knee replacement better than total hip replacement? AB - Revision rates, complication rates, and the bone-cement interface reaction of 1,069 condylar total knee replacements were reviewed to help decide if conventional total knee replacement continues to be appropriate for the older low demand patient. This knee replacement series was also compared with two published series of total hip replacements from the same institution. The conclusions are (1) in medium-term follow-up, total knee replacement is as good as or superior to total hip replacement and (2) based on bone-cement interface analysis, survival of total knee replacement is expected to be superior to conventional total hip replacement ten years postoperatively. PMID- 2919083 TI - Press-fit condylar total knee replacement. AB - In 1984 the press-fit condylar knee was first introduced and was intended to provide a condylar knee system primarily for posterior cruciate retention that addressed refinements in metallurgy, prosthetic geometry and sizing, cementless fixation, inventory management, and instrumentation. This article addresses the results observed in the use of this prosthesis. PMID- 2919084 TI - A comparison of cemented and cementless fixation with the Miller-Galante total knee arthroplasty. AB - This study demonstrates the comparability of cemented and cementless fixation in total knee arthroplasty at short-term follow-up. While some differences in pain, limp, and support were noted, knee scores were equivalent. Roentgenographic analysis as well as implant retrieval studies demonstrate that porous ingrowth is a viable method of fixation of total knee components. Further long-term follow-up studies will be required to determine both the long-term clinical results and the longevity of the fixation interface. PMID- 2919085 TI - [Scintigraphy of the adrenergic nervous system]. AB - The authors describe their experiences with 100 MIBG scintigraphies. The importance of the examination is stressed in the diagnostics of neuroblastoma in childhood, the determination of the clinical stage and follow-up of the disease. MIBG scintigraphy plays a primary role among the imaging examination procedures aimed at the localization of pheochromocytoma especially in the extra-adrenal, multiplex and malignant diseases. The disturbance of adrenergic innervation in Shy-Drager syndrome is demonstrable with radiopharmacon. PMID- 2919086 TI - [Measurement of aortic flow indices by Doppler echocardiography for the determination of systolic function in infants and children]. AB - Aortic blood flow velocity indexes measured by Doppler echocardiography to assess systolic function in infants and children. The obtained M-mode parameters were correlated with Doppler findings. We found the closest correlation between lin. EF and peak flow velocity integral (r = 0.83 p less than 0.001) Echocardiography completed by Doppler studies proved to be a safe noninvasive method not only estimating left ventricle dysfunction but in assessment the changes in the follow up too. PMID- 2919087 TI - ["Tell the world what you are doing against AIDS!"]. PMID- 2919088 TI - [The work of the nationwide network of Genetic Counseling Services in Hungary between 1978 and 1985]. PMID- 2919089 TI - Antinociceptive effects of azepexole (BHT 933) in mice. AB - Subcutaneous (s.c.) administration of azepexole (BHT 933) at doses between 4 and 40 mg/kg produced dose-dependent antinociceptive effects in mice as assessed by tail-immersion, tail-pinch and acetic acid writhing tests. The ED16s were 5.6 +/- 0.4, 6.7 +/- 1.2 and 2.96 +/- 0.2 mg/kg respectively. Similarly, morphine produced analgesia in the same tests with ED16s of 0.87 +/- 0.03, 0.47 +/- 0.1 and 0.45 +/- 0.01 mg/kg respectively. In all instances naloxone (0.1 mg/kg s.c.) shifted the dose-response curves to morphine to the right in a parallel manner. Naloxone (0.1 and 1 mg/kg s.c.) partially antagonized the effect of azepexole in the tail-immersion and tail-pinch tests but significantly decreased the slope of the dose-response curve suggesting that a competitive interaction at the level of the opioid receptors did not occur. Naloxone had no effect on the antinociceptive action of azepexole in the acetic acid writhing test. PMID- 2919090 TI - Diurnal variations in pain perception and thermal sensitivity. AB - Pain and thermal sensitivity thresholds in healthy volunteers were examined for diurnal variations. The subjects were 11 men aged between 22 and 27 years (means = 23.5, S.D. = 1.5). Data were collected for 2 days, with 7 measurements per day. To ensure the pain specificity of the results the subliminal modality, i.e., thermal sensitivity thresholds to warm and cold stimuli, was investigated in addition to the threshold for perception of heat pain. Assessments were made on the right hand and foot, the stimuli being presented with a thermoelectric contact-thermode. Despite the influence of variables other than time of day (45 56% of the total variance), diurnal variations were found for some subjects on the pain threshold measure (significant correlation between days and relatively high frequency of 24 h component in Fourier analysis spectra). However, they could not be demonstrated for the thermal sensitivity measures. The diurnal variations in pain perception thresholds did not have a consistent pattern over all subjects (Friedman test). The small diurnal variations with interindividual differences in the pattern are therefore not sufficient to explain the variations seen in clinical pain, but they may be useful in detecting pain modulators by investigating correlations. PMID- 2919092 TI - On the difficulties of coding pain-related data. PMID- 2919091 TI - Central post-stroke pain--neurological symptoms and pain characteristics. AB - The intention of the present study was to characterize patients with central post stroke pain (CPSP) with regard to type and location of the cerebrovascular lesion (CVL), the characteristics of the pain and the neurological symptoms and signs in addition to the pain. Twenty men and 7 women with a mean age of 67 years and a mean pain duration of 44 months were examined 9-188 (mean 53) months after their stroke. The clinical symptoms and signs and the CT scans indicated that the CVL were located in the lower brain-stem in 8 patients, involved the thalamus in 9 patients and were located lateral and superior to the thalamus in 6 patients. In the remaining 4 patients the location of the CVL could not be determined with certainty. The 3 identified hematomata were all located in the thalamus. The onset of the pain was immediate in 4 patients, within the first post-stroke months in 10 patients and delayed by 1-34 months in the rest. The pain was on the left side in 18 patients. Twenty patients had hemipain. Most patients experienced more than one type of pain. The most common qualities were burning, aching, pricking and lacerating, with some differences in the frequencies according to the location of the CVL. Burning pain was most common, except among the patients with thalamic CVL, in whom lacerating pain was more common. Aching and pricking pain were also frequent. All patients considered the pain to be a great burden and most rated the pain intensity as high on a visual analogue scale. The intensity was increased by external stimuli, the most common being joint movements, cold and light touch. Five patients reported aggravation by emotional stimuli. Besides pain, the only neurological symptom common to all patients was decreased temperature sensibility, as shown by quantitative methods. It is possible that pain sensibility was also abnormal in all. Hypersensitivities to cutaneous stimuli, including evoked dysesthesias were found in 88% of the patients, while the detection thresholds for touch and vibration were abnormal in only 52% and 41%, respectively. Similarly, low figures were found for paresis and ataxia, which were present in 48% and 62%, respectively. It is concluded that only a minority of patients with central pain after stroke have thalamic lesions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2919093 TI - Comparison of ketamine and pethidine in experimental and postoperative pain. AB - The analgesic efficiency of ketamine and pethidine was compared in experimental ischemic pain and postoperative pain after oral surgery. Naloxone 1.6 mg or placebo was given 5 min before the analgesic drug. The subjects recorded their pain on a visual analogue scale. Both ketamine 0.3 mg/kg and pethidine 0.7 mg/kg were effective as analgesics against the two types of pain studied. Naloxone prevented the analgesic effect of pethidine, but had no effect on ketamine analgesia. The results are in accordance with the hypothesis that the analgesic effect of ketamine is mediated by a non-opioid mechanism, possibly involving PCP receptor-mediated blockade of the NMDA-receptor-operated ion channel. PMID- 2919094 TI - Dynamics and significance of placebo response in primary dysmenorrhea. AB - A total of 55 patients with primary dysmenorrhea who had shown a favorable response to a preliminary treatment cycle with placebo were admitted to a double blind study on placebo versus antiprostaglandin agents (naproxen and pirprofen). To evaluate the placebo effect and its duration, the treatment was given for 4 successive cycles. Whereas the antiprostaglandin agents were effective in most of the patients (in 80% of the pirprofen group and 85.7% of the naproxen group) and this efficacy was maintained throughout the study, a favorable response to placebo was observed in 84% in the first cycle, 29% in the second, 16% in the third and 10% in the fourth. The incidence of side effects was similar in the placebo and the active treatment groups (35.4% vs. 37.5%). It is postulated that a placebo effect in dysmenorrhea is due to a central analgesic mechanism mediated by endorphin release or possibly to psychological dynamics (mental or conditioning theories). However, this effect loses efficacy with time possibly due to a decreased susceptibility to the opioid action of the central nervous circuits responsible for menstrual pain perception or to deconditioning mechanisms. PMID- 2919095 TI - An epidemiological follow-up survey of persistent pain sufferers in a group family practice and specialty pain clinic. AB - The course and prognosis of persistent pain are largely unknown. In addition, follow-up studies of chronic pain sufferers have come from specialized pain clinics and have ignored the question of how representative this special group is to the general population who suffer persistent pain. Because health care planners are assumed to require these data for projection of health care needs, it is important to determine the course of persistent pain in those persistent pain sufferers in the general population as well as those referred to a specialty clinic. An epidemiological study compared 2 groups of self-reported persistent pain sufferers from a Family Practice Clinic and a Specialty Pain Clinic over a 2 year period. All subjects reporting a persistent problem with pain at the time of the initial survey were contacted 2 years later to determine whether the initial differences between the 2 groups remained constant over time and whether there were any changes within each group over time. Despite the similarities between the study groups on multiple socioeconomic and demographic variables, the Specialty Pain Clinic group remained distinctly different from the Family Practice pain sufferers on many pain behavior and emotional variables. Thirteen percent of the persistent pain sufferers from the Pain Clinic group and 36% of the persistent pain sufferers from the Family Practice group no longer reported pain as a problem at follow-up. Of those pain sufferers from either group who continued to experience pain at 2 years follow-up, their pain became more intermittent, psychological distress factors improved, and the use of health services decreased. The implications are that persistent pain does not necessarily continue forever and that persistent pain sufferers in the general population have a better prognosis than those who are referred to a Specialty Pain Clinic. All follow-up studies need to be interpreted in light of these findings. PMID- 2919096 TI - The detection of psychiatric illness and psychological handicaps in a British pain clinic population. AB - Ninety-seven successive patients attending the Newcastle Pain Relief Clinic completed a battery of psychiatric, psychological and pain questionnaires, and an extensive personal information form. All patients were seen by a physician who evaluated the extent of the pain arising from physical, psychiatric and psychological causes, and by a psychiatrist, who administered a structured interview schedule. Thirty-two percent of the patients had sufficient symptoms to be classified as psychiatric cases on the Present State Examination (PSE), a further 22% had minor neurotic symptoms and features of illness behaviour, 35% were categorized as organic, and 11% were unclassified. The Leeds General Depression Scale for Depression and Anxiety and the Beck Depression Inventory were the most effective of the psychiatric questionnaires used in separating the psychiatric patients from the remainder, and can be recommended as screening instruments for psychiatric illness in this population. Factors associated with a psychiatric diagnosis included female sex, larger number of present medications, greater reduction in activities compared to the period before the pain developed and increasing subjective pain from the onset of this. PMID- 2919097 TI - Relationships between depressive symptoms and descriptions of chronic pain. AB - The present study investigated the relationship between the severity of depressive symptoms and various qualitative and quantitative aspects of pain reported by chronic pain patients. The sample consisted of 73 patients from a heterogeneous pain population admitted to the Victoria General Hospital Pain Management Unit. Patients completed a comprehensive pain evaluation battery that included the Beck Depression Inventory (BDI) and the McGill Pain Questionnaire (MPQ). They rated their loss of desire and ability for various social and recreational activities, and the intensity of their pain for 8 periods of a typical day. Multivariate analyses of variance were used to assess the sensory, affective, and evaluative indices of the MPQ, daily pain intensity ratings, and reported impairment of activities of non-depressed, mildly depressed and moderate/severely depressed patients. The results indicate significant relationships between the degree of depression and (a) the number of sensory descriptors endorsed on the MPQ; (b) pain intensity ratings in the late evening and at bedtime; and (c) reported loss of ability for social and recreational activities. Depression is related to loss of desire for activity in women, but not in men. A discriminant analysis suggests that depressed and non-depressed pain patients can be distinguished with 78% accuracy on the basis of their MPQ Sensory scores, reported loss of ability for activities, and global pain ratings at late evening and bedtime. The findings are discussed in terms of their implications for research as well as for the assessment and treatment of chronic pain patients. PMID- 2919098 TI - Pain in mitral valve prolapse. AB - Thirty subjects with mitral valve prolapse were carefully observed, in order to investigate whether chest pain, characteristic of angina pectoris, was present. No cases of angina pectoris or of heart pain were observed. A characteristic which did emerge was that 86% of the subjects suffered a typical myofascial pain of the muscles of the chest. There does not appear to be a clear relationship between mitral valve prolapse and myofascial pain. PMID- 2919099 TI - Continuing care: a major issue in cancer pain management. PMID- 2919100 TI - Extent of sympathetic blockade after stellate ganglion block with bupivacaine. AB - A study of the extent of sympathetic blockade after stellate ganglion block was assessed using liquid crystal thermography. Two volumes (10 and 20 ml) of bupivacaine 0.5% plain were used. Irrespective of the volume used cranial sympathetic block always occurred and thoracic sympathetic block never occurred. While upper cervical block was present in all patients, lower cervical sympathetic block was present only in the 20-ml group (P less than 0.05). The larger volume was associated with a significant incidence of hoarseness due to spread of local anaesthetic onto adjacent laryngeal nerves. PMID- 2919101 TI - Effects of extraversion and neuroticism on experimental pain, clinical pain, and illness behavior. AB - The effects of 2 personality traits, extraversion and neuroticism, on experimental and clinical pain were characterized in a group of myofascial pain dysfunction (MPD) patients. Extraverts did not differ from introverts in visual analogue scale (VAS) sensory or VAS affective ratings of graded 5-sec nociceptive temperature stimuli (43-51 degrees C) nor in VAS sensory-VAS affective relationships related to their clinical pain. However, high extravert patients scored lower on affective inhibition (Pilowsky Illness Behavior Questionnaire; IBQ) compared to low extravert patients. This result is consistent with previous suggestions that extraverts inhibit overt expressions of suffering less than do introverts. High neurotic patients did not differ from low neurotic patients in their VAS sensory ratings of either experimental or clinical pain. Their VAS affective ratings of both types of pain were marginally higher as compared to low neurotic patients. As hypothesized, high neurotic score patients gave higher VAS ratings of emotions related to suffering and scored higher on items related to affective disturbance on the IBQ as compared to low neurotic score patients. Overall, the results indicate that the personality traits of neither extraversion nor neuroticism affect sensory mechanisms of nociceptive processing but appear to exert their influence by means of cognitive processes related to the ways in which people constitute the meanings and implications of pain. PMID- 2919102 TI - Caudal epidural morphine analgesia for an infant with advanced neuroblastoma: report of a case. AB - Caudal epidural administration of morphine was used to provide pain relief to a 5 month-old infant with neuroblastoma and massive abdominal distension. Intermittent injections were performed on 6 occasions over 1 week and resulted in prolonged analgesia (17-20 h) and improved depth of respiration on each occasion. Epidural opioid analgesia should be regarded as technically feasible for relief of cancer pain in patients of all ages. PMID- 2919103 TI - Effects of diffuse noxious inhibitory controls (DNICs) on the sensory discriminative dimension of pain perception. AB - We have recently demonstrated that humans report heat stimuli as less painful when presented concurrently with a second noxious stimulus applied to another part of the body. Previous neurophysiological studies have shown that similar heterotopically applied noxious stimuli selectively and completely inhibit the activity of wide-dynamic-range (WDR) neurons in the dorsal horn - a phenomenon termed diffuse noxious inhibitory controls (DNICs). Taken together, these 2 lines of evidence suggest that activation of WDR cells may be necessary for normal perception of pain. Recent studies in the behaving monkey have additionally shown that WDR neurons respond to small changes in noxious heat stimuli better than do high threshold neurons, thus indicating a more specific role for WDR neurons in sensory-discriminative aspects of pain perception. If DNICs do indeed selectively and completely inhibit the activity of WDR neurons, then a heterotopically applied noxious stimulus should selectively interfere with a subject's ability to discriminate noxious stimuli. This hypothesis was tested using a noxious heat discrimination task and a cold water (5 degrees C) diffuse noxious stimulus. We found that the ability to detect small changes (0.4-0.8 degrees C) in painful heat stimuli applied to the face decreases when the person's hand is submerged in painfully cold water (P = 0.005) and that this effect persists, to a lesser extent, after the hand is removed from water. Control tasks, using visual stimuli, demonstrated that the modulation of nociceptive discrimination was not a generalized effect on sensory perception; other control measures indicated that the results could not be attributed to distraction, fatigue or changes in response bias.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2919104 TI - Long-term changes in discharge behaviour of cat dorsal horn neurones following noxious stimulation of deep tissues. AB - Certain pathological types of afferent input are supposed to lead to long-term changes in the responsiveness of dorsal horn neurones. This mechanism might be of importance for the development of neurological disturbances such as chronic pain. The present study was undertaken in order to find out whether dorsal horn neurones--particularly those processing input from deep tissues--exhibit long lasting changes in response behaviour after a short-lasting noxious stimulation of deep tissue. In anaesthetized cats, the impulse activity of single dorsal horn cells was recorded extracellularly with glass microelectrodes. In a small number of cells that had multiple receptive fields (RFs), the algesic agent bradykinin was injected into a muscle RF and the properties of all RFs retested at regular time intervals. Following noxious chemical stimulation of one RF, the injected and the other RFs of the same neurone often showed changes which consisted of an increase in size, a lowering of mechanical threshold and appearance of new RFs. In an attempt to assess the influence of a single noxious stimulus on the entire population of dorsal horn cells, the properties of a greater sample of neurones were compared before and after injection of bradykinin into the deep tissues of the hind limb. Every cell encountered was classified as being driven by (1) cutaneous receptors only, (2) deep receptors only, (3) both input sources, or (4) electrical stimulation only (cell without receptive field). Following injection of bradykinin, the proportion of cells with both deep and cutaneous input and of those having background activity rose, and the percentage of cells without a receptive field decreased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2919105 TI - Influence of a specific 5-HT3 antagonist on carrageenan-induced hyperalgesia in rats. AB - The effect of ICS 205-930 (ICS), a specific 5-HT3 antagonist, was studied on carrageenan (CAR)-induced rat paw inflammation to assess the involvement of endogenous released serotonin (5-HT) in the observed hyperalgesia. Studies were performed using a behavioural test, measuring the threshold stimulus necessary to elicit vocalization by gradually increasing pressure applied to the paw. When administered (s.c., in the CAR-injected paw) either 20 min before, simultaneously or 20 min after CAR, ICS (10(-11) mol/kg, i.e., 3.2 ng/kg) completely prevented the hyperalgesia in both the injected and non-injected hind paws. This effect was prolonged for 90 min, equivalent to the effect on CAR on 5-HT release. Moreover, ICS increased the vocalization threshold over the pre-drug values in normal and CAR-treated rats when injected both 20 min before and simultaneously with the polysaccharide. On the contrary, it did not reduce the hyperalgesia, when injected 2 h after CAR. ICS had no effect at any time of administration on paw oedema. These results suggest that the early inflammatory sensitization of peripheral nociceptors is mainly dependent on the release of serotonin and that the hyperalgesic effect of the monoamine involves 5-HT3(M) receptors which do not seem to be involved in the early development of oedema. PMID- 2919106 TI - Buspirone effect on the development of antinociceptive reactions. AB - The anxiolytic agents, buspirone and diazepam, increase the paw lick latency of rats in the hot plate test, the effect being dose-dependent and exceeding that of morphine. The action of buspirone was not accompanied by ataxic and sedative effects which were observed in rats on diazepam. Buspirone (up to 25 mg/kg) and diazepam (up to 5 mg/kg) neither change the tail flick latency nor potentiate the action of morphine on the test. A buspirone dose of 2 mg/kg administered to animals before foot shock, or the dose of 1.5 mg/kg before cold swimming stress, led to a significant increase in hot plate latency 1 min after stress as compared to the control. The effect of buspirone on the paw lick reaction in rats may be related to the activation of antinociceptive mechanisms and inhibition of an emotional-motivational component of the pain reaction. PMID- 2919107 TI - Opposing effect of apomorphine on antinociceptive activity of morphine: a dose dependent phenomenon. AB - Apomorphine, when administered intracerebroventricularly (0.05 mg/kg) to rats, increased tail-flick latency (a spinal nociceptive response). However, intraperitoneal administration at doses of 1, 3 and 10 mg/kg had no effect, probably because of a tonic supraspinal inhibitory influence on spinal dopaminergic neurones involved in segmental nociceptive processes. Depending on the doses administered, intraperitoneal administration of apomorphine exhibited opposite effects on antinociceptive activity of morphine. Pretreatment with a low dose of apomorphine (1 mg/kg) attenuated, whereas, a high dose (10 mg/kg) potentiated morphine-induced antinociception. Dopamine antagonists, in doses that preferentially block autoreceptors, i.e., haloperidol (0.1 mg/kg, i.p.) and (-) sulpiride (5 mg/kg, i.p.), antagonised the attenuation of morphine antinociception by a low dose of apomorphine, while treatment with a high dose of haloperidol (1 mg/kg, i.p.) and pimozide (1.25 mg/kg, i.p.) completely antagonised the potentiating effect of a high dose of apomorphine on the antinociceptive activity of morphine. The attenuation of morphine antinociception thus appears to be due to decreased dopaminergic activity as a result of preferential dopamine autoreceptor stimulation by a low dose of apomorphine, whereas potentiation with a high dose of apomorphine is caused by enhanced dopaminergic activity via postsynaptic receptor stimulation. PMID- 2919108 TI - Training pediatric scientists. PMID- 2919109 TI - Disposition of ethanol and acetaldehyde in late pregnant rats and their fetuses. AB - The pattern of ethanol and acetaldehyde appearance in blood after an oral ethanol gavage (4 g/kg body wt) was not different at 12 or 21 days' gestation compared to virgin rats. Five min after maternal ethanol administration, concentrations of ethanol in fetal blood were lower than in maternal blood; however, at 15 min after ethanol administration, fetal and maternal blood levels were similar. Ethanol concentrations in fetal blood and amniotic fluid were already at equilibrium 5 min after ethanol administration. Acetaldehyde concentrations in fetal blood and in amniotic fluid were undetectable at all the times investigated, with the exception of fetuses from two pregnant rats studied 3 h after ethanol administration. Alcohol dehydrogenase activity in fetal liver and in placenta at late pregnancy was very low or undetectable, suggesting a very low rate of ethanol oxidation in vivo. After intravenous administration of acetaldehyde (10 mg/kg body wt), blood acetaldehyde concentrations were higher in pregnant than in virgin rats. Acetaldehyde concentrations in fetal blood and in amniotic fluid were similar to maternal blood at 2, 5, and 30 min after injection. When circulating concentrations of maternal and fetal acetaldehyde, obtained after either ethanol or acetaldehyde administration, were plotted, it was found that fetal blood concentrations of acetaldehyde were only detectable when maternal blood concentrations were greater than 80 microM. Concerning the acetaldehyde oxidation capacity, both the high and low affinity components of aldehyde dehydrogenase activity in fetal liver and placenta were very low as compared with maternal liver. However, aldehyde dehydrogenase activity in fetal liver was much higher than in placenta.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2919110 TI - Intestinal maturation: characterization of mitochondrial calcium transport in the rat. AB - The mitochondria play a major role in the regulation of intracellular calcium. Despite the fact that the enterocytes receive the majority of absorbed calcium, the role of the intestinal mitochondria in calcium transport during maturation is not known. Therefore, the current studies were designed to characterize calcium pump activity of jejunal mitochondria of rats during maturation (suckling, weanling, and adolescent rats). The functional integrity of the intestinal mitochondria of suckling and adolescent rats was determined by oxygen consumption studies demonstrating respiratory control ratios of more than 3 when succinate was used as a test substrate. Ca++ uptake was significantly stimulated by the presence of 3 mM ATP at all age groups studied. Maximal Ca++ uptake in the presence of 3 mM ATP and 2 mM succinate was 31.1 +/- 0.4, 50.2 +/- 4.2, and 94.3 +/- 1.5 nmol/mg protein (mean +/- SE) in suckling, weanling, and adolescent rats, respectively. Rates of ATP hydrolysis were 15.5 +/- 1.5 and 2.9 +/- 0.3 nmol/ATP hydrolyzed/mg protein in adolescent and suckling rats, respectively (p less than 0.001). Ca++ uptake was completely inhibited by 0.25 microM ruthenium red, oligomycin (10 micrograms/mg protein), 0.5 mM dinitrophenol and 1 mM sodium azide at all age groups. Ca++ efflux in the presence of ruthenium red occurred by a Na+ dependent pathway, indicating a Ca++/Na+ exchange mechanism. Kinetic parameters for ATP stimulated Ca++ uptake at 10 s revealed a Km of 0.84 +/- 0.11, 0.65 +/- 0.17, and 0.57 +/- 0.03 microM and Vmax of 1.83 +/- 0.07, 3.62 +/- 0.26 and 14.15 +/- 0.21 nmol/mg protein/10 s in suckling, weanling, and adolescent rats, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2919111 TI - Interrelation between the metabolism of L-isoleucine and L-allo-isoleucine in patients with maple syrup urine disease. AB - The nonprotein amino acid L-allo-isoleucine is formed endogenously in maple syrup urine disease patients from (R)-3-methyl-2-oxo-pentanoic acid. During strict metabolic balance, the plasma L-allo-isoleucine/L-isoleucine ratio correlates inversely with the residual activity of the branched-chain 2-oxoacid dehydrogenase in fibroblasts and thus constitutes a relevant in vivo parameter of the severity of the metabolic defect in MSUD patients. PMID- 2919112 TI - Characteristics of histidine uptake by human placental microvillous membrane vesicles. AB - L-histidine is an essential amino acid. Its fetal-to-maternal blood concentration ratio is high, suggesting active placental transport. In this study, human placental microvillous membrane vesicles were used to characterize L-histidine transport, heretofore not evaluated in human tissue. L-Histidine uptake by microvillous membrane vesicles was stimulated by an inward sodium gradient, leading to an "overshoot," followed by apparent equilibration. Linear uptake at 22 degrees C was limited to the 1st min. The initial sodium-dependent uptake rate was proportional to the sodium concentration in the medium. The sodium-dependent uptake was markedly diminished or lost when potassium, cesium, or choline was substituted for sodium but not lithium. Replacement of chloride with sulfate or gluconate had little effect. Sodium-stimulated L-histidine uptake was further stimulated by an outward potassium gradient (inside-negative) in the presence of valinomycin. Sodium-dependent uptake kinetic constants for L-histidine were: Km = 0.44 +/- 0.18 mM: Vmax = 536 +/- 94 nmol/mg/30 s (mean +/- SD). 2 (methylamino)isobutyric acid did not inhibit L-histidine uptake. Conversely, L histidine noncompetitively inhibited sodium-dependent uptake of 2 (methylamino)isobutyric acid and L-cysteine. L-glutamine competitively inhibited sodium-dependent L-histidine uptake. L-histidine uptake was stimulated by preloading the vesicles with either L-histidine or L-glutamine (transstimulation). L-histidine uptake was not sensitive to N-ethylmaleimide treatment but was strongly inhibited by low pH. These findings suggest that L histidine is transported in the human placenta by a specific sodium-dependent system similar to the "N" system described in rodent hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2919113 TI - The effect of diazepam on neonatal seizure: in vivo 31P and 1H NMR study. AB - It is assumed that when anticonvulsants arrest seizure, there is rapid return of brain high energy phosphates and brain lactate to control values. To test this hypothesis, diazepam was administered to neonatal dogs during flurothyl-induced seizure. In vivo 31P nuclear magnetic resonance spectroscopy disclosed that diazepam quickly arrested electrographic seizure and restored brain phosphocreatine and inorganic phosphate to baseline values. In contrast, in vivo 1H nuclear magnetic resonance spectroscopic measurements showed that arrest of seizure with diazepam did not return brain lactate to control values. The sustained increase in cerebral blood flow and prolonged elevation of brain lactate, acetate, valine, and succinate in the postictal period indicate that metabolic recovery of the brain occurs over an extended period of time after the normalization of EEG, phosphocreatine, and brain pH. PMID- 2919114 TI - Gestational effects of corticosteroids and surfactant in ventilated rabbits. AB - Maternal corticosteroid treatments decreased lung protein leaks and increased the compliance responses to exogenous surfactant in 27-day preterm rabbits. We asked if maternal corticosteroid treatments at different gestational ages might alter these responses. Pregnant does were given 0.1 mg/kg betamethasone 48 and 24 h before study of the rabbits at 27, 28, and 29 days of gestational age and term newborns at 31 days of gestational age. Alternate rabbits at each gestation were treated with 50 mg/kg surfactant after delivery. Alveolar saturated phosphatidylcholine pool sizes increased with gestation similarly in control and corticosteroid-treated groups. Corticosteroids improved compliance relative to control values at 29 days of gestational age in animals not treated with surfactant and improved the compliance response to surfactant treatment at 27 and 28 days of gestational age. Corticosteroids decreased the leak of radiolabeled albumin to the lungs and alveolar washes at all preterm gestations with a maximum decrease to 16% of the control value at 29 days of gestation. Surfactant decreased this protein leak more effectively than did corticosteroids at the earlier gestations. There were potentially beneficial effects of corticosteroids either alone or together with surfactant at all preterm gestations studied. No protein leak or compliance effects of either treatment were noted in the term newborns. PMID- 2919115 TI - Short-chain acyl-coenzyme A dehydrogenase deficiency in mice. AB - A murine model for short-chain acyl-coenzyme A dehydrogenase (SCAD) deficiency has been identified and characterized in BALB/cByJ mice. These mice have undetectable SCAD activity, severe organic aciduria; excreting ethylmalonic and methylsuccinic acids and N-butyrylglycine, and develop a fatty liver upon fasting or dietary fat challenge. The mutant mice develop hypoglycemia after an 18-h fast, and have elevated urinary and muscle butyrylcarnitine concentrations. Most of these findings parallel those of human disorders associated with SCAD deficiency and other beta-oxidation defects. This mouse model presents important opportunities to investigate the biology of mammalian fatty acid metabolism and the related human diseases. PMID- 2919116 TI - Circulatory effects of sodium nitroprusside in the conscious lamb with an aortopulmonary left to right shunt. AB - We studied the effect on the circulation of reducing peripheral vascular resistance by infusing sodium nitroprusside into lambs of three different age groups (subgroup A, 11-26 days, subgroup B, 32-52 days, and subgroup C, 61-88 days of age) with and without an aortopulmonary left to right shunt. Infusion of 10 micrograms/kg/min nitroprusside over 2 h decreased aortic and left atrial pressures markedly and increased heart rate, whereas systemic, pulmonary, and left to right shunt blood flows hardly changed. Within 30 min after the onset of infusion, the hemodynamic variables stabilized. Aortic and left atrial pressures were still below control levels at that time. The different flows remained the same and heart rate, after an initial fall, increased again. The pattern of hemodynamic changes was not influenced by age or the presence of an aortopulmonary left to right shunt. Based on this study, we do not advocate sodium nitroprusside administration in case of a left to right shunt with normal arterial pressure and systemic blood flow. PMID- 2919117 TI - Serum mucin-associated antigen levels of cystic fibrosis patients are related to their ages and clinical statuses. AB - Mucin levels are generally elevated in sera from many cystic fibrosis (CF) patients as measured by radioimmunoassay using monoclonal antibody 19-9, which is directed against the mucin-associated sialyl Lea antigen. Antibody 19-9 can only be used to measure mucin-associated antigen levels in those patients who are genetically able to make detectable levels of mucin-associated sialyl Lea epitope. Serial studies of 20 patients followed over 3-5 y showed that their serum mucin-associated antigen levels varied directly with respect to the severity of their disease and inversely with their Shwachman-Kulczycki clinical scores (p less than 0.001) and Brasfield chest roentgenographic scores (p less than 0.02). Serum mucin-associated antigen levels in samples from 89 CF patients were generally higher in the older patients (p less than 0.025). Serum mucin associated antigen levels of CF patients who were colonized with Pseudomonas aeruginosa did not significantly differ from those of uninfected CF patients. The mean serum mucin-associated antigen level of CF patients colonized with Pseudomonas was higher than the mean mucin level of six non-CF bronchiectatic patients whose lungs were colonized with Pseudomonas (p = 0.053). Serum mucin associated antigen levels are thus related to CF patients' ages and clinical statuses. PMID- 2919118 TI - Copper toxicity and lipid peroxidation in isolated rat hepatocytes: effect of vitamin E. AB - We investigated the role of lipid peroxidation as the mechanism mediating copper toxicity in isolated rat hepatocytes and the modulating effect of vitamin E. Hepatocytes, isolated from rats fed diets containing deficient (E-), sufficient (E+), and excess (E++) amounts of vitamin E, were incubated with CuCl2 (0-2400 microM) for 150 min. Dose and time-dependent decreases in hepatocyte viability (determined by trypan blue exclusion and lactate dehydrogenase release) due to copper toxicity correlated with production of malonyldialdehyde in E- and E+ hepatocytes. However, malonyldialdehyde generation did not accompany copper toxicity in E++ cells. Copper toxicity was enhanced in E- compared to E+ and E++ hepatocytes as assessed by cell viability studies and ultrastructural plasma membrane bleb formation. In vitro vitamin E repletion of E- hepatocytes restored resistance to copper and decreased malonyldialdehyde production proportionately. Thus vitamin E deficiency appeared to increase the susceptibility of hepatocytes to copper toxicity. We conclude that lipid peroxidation may not be the mechanism by which copper is toxic to isolated hepatocytes but that the site of injury may be thiol-rich cellular proteins. PMID- 2919119 TI - Heterogeneity of Fc receptor expression in chemotaxis and adherence of neonatal neutrophils. AB - Chemotaxis and adherence to polymorphonuclear neutrophils (PMN) subpopulations from cord blood of 13 healthy neonates and blood of 16 healthy adults as control subjects were determined using the rosette-forming procedure, the modified Boyden method, and 51Cr adherence assay. The percentage of rosette-forming neutrophils (RFN) (Fc receptor expression) of cord PMN (35 +/- 8%) was significantly lower than that of adult PMN (60 +/- 4%, p less than 0.01). Differences in chemotaxis of PMN subpopulations between cord and adult PMN after stimulation by their own endotoxin-activated plasma were as follows: (i) unfractionated adult PMN (A) (n = 10) versus adult RFN (B) (n = 5) versus adult nonRFN (C) (n = 5); (A) less than (B), p less than 0.01 and (A) greater than (C), p less than 0.01; (ii) unfractionated cord PMN (a) (n = 5) versus cord RFN (b) (n = 5) versus cord non RFN (c) (n = 5); (a) less than (b), p less than 0.01 and (a) versus (c), NS; (iii) (A) greater than (a), p less than 0.01; (iv) (B) greater than (b), p less than 0.05 and (C) versus (c), NS. Similarly, differences in adherence were as follows: (i) (A) (n = 13) versus (B) (n = 4), NS and (A) greater than (C) (n = 4), p less than 0.01; (ii) (a) (n = 4) versus (b) (n = 4), NS and (a) greater than (c) (n = 4), p less than 0.01; (iii) (A) greater than (a), p less than 0.05; (iv) (B) versus (b), NS and (C) versus (c), NS. These results suggest that differences in chemotaxis and adherence between cord and adult PMN may relate in part to differences of PMN subpopulations. PMID- 2919120 TI - Human lactation. II: Endogenous fatty acid synthesis by the mammary gland. AB - We studied the effects of a diet that was low in fat, high in carbohydrate (CHO) on milk lipid composition and de novo endogenous fatty acid synthesis by the mammary gland in five lactating women. The women consumed either a low fat (LF) (5% fat, 80% CHO) diet or a high fat (HF) (40% fat, 45% CHO) diet. Fat synthesis was determined after an oral dose of 500 mg/kg D2O by measuring the incorporation of deuterium into C10:0 to C18:0 saturated fatty acids of milk fat and plasma triglycerides by gas chromatography-mass spectrometry. Synthesis of plasma C16:0 and C18:0 triglycerides was barely detectable while women consumed the HF diet, but was increased 6-fold during the LF diet. Medium chain fatty acids secreted by the mammary gland increased from 12.8% (HF diet) to 16.3% (LF diet) in milk fat from four of five subjects (p = 0.027). Medium chain fatty acid secretion, however, increased from 13.9% (HF diet) to 29.9% (LF diet) in one subject. The primary fatty acids synthesized during lactation were C10:0, C12:0, and C14:0 in the majority of women studied. The LF diet significantly increased the apparent synthesis of C14:0 (p = 0.05), whereas no changes were observed in C12:0, C16:0, or C18:0. One subject had highly enriched C16:0 and C18:0 fatty acids in her milk on the LF diet, which could have been the result of mammary synthesis or of transport and secretion of hepatically synthesized lipids. PMID- 2919121 TI - Increased constriction of the ductus arteriosus with combined administration of indomethacin and betamethasone in fetal rats. AB - To find a better treatment for patient ductus arteriosus of preterm infants, we studied the combined effect of indomethacin and betamethasone on the fetal ductus in rats. We used a rapid whole-body freezing technique, and the ratio of the inner diameter of the ductus to the main pulmonary artery, which was 1.0 in controls, was used as an index of constriction. Indices of ductal constriction 4 h after administration of indomethacin (1 mg/kg) alone, betamethasone (1 mg/kg) alone or in combination in near-term rats were 0.56 +/- 0.05 (mean +/- SEM), 0.76 +/- 0.06, and 0.17 +/- 0.03, respectively. In preterm rats too, a marked increase in fetal ductus constriction was observed with the combined administration of these two drugs. Study of the dose effect of betamethasone revealed that maximal effects were obtained with 1 mg/kg of betamethasone combined with indomethacin in both preterm and near-term fetal rats. Increased constriction of the fetal ductus with combination treatment persisted from 1 to 8 h after administration. Administration of betamethasone 24 h before the rat was killed did not augment constriction of the fetal ductus by indomethacin administered 4 h before they were killed. Fetal ductus constriction by sulindac, another nonsteroidal antiinflammatory drug with little inhibitory effect on renal function, also was augmented by combined use with betamethasone (1 mg/kg). In conclusion, ductal constriction was markedly increased by combined administration of indomethacin and betamethasone in near-term and preterm fetal rats. PMID- 2919122 TI - Effect of somatomedin-C/insulin-like growth factor I and growth hormone on cultured growth plate and articular chondrocytes. AB - To determine whether growth hormone has a direct effect on skeletal tissues not mediated by somatomedins, and to better define the role of somatomedin-C/insulin like growth factor I (Sm-C/IGF-I) in skeletal development, bovine growth plate, and rabbit articular and growth plate chondrocytes in primary culture were evaluated under a variety of experimental conditions designed to elicit growth hormone and Sm-C/IGF-I stimulation. Under none of these conditions did bovine growth plate chondrocytes respond to either homologous bovine growth hormone or heterologous hGH. Under the same conditions, these cells were highly responsive to human Sm-C/IGF-I with respect to both [3H]thymidine and [35S]sulfate incorporation, indices of mitotic and differentiated cell functions, respectively. Similarly, both rabbit articular and growth plate chondrocytes showed enhanced incorporation of [3H] thymidine and [35S]sulfate in the presence of Sm-C/IGF-I, but did not respond to either native or recombinant hGH. Cells at different stages of maturation within the bovine growth plate differed in their reaction to Sm-C/IGF-I with proliferative zone cells manifesting a greater response to the peptide than cells of the reserve zone. These results suggest that the action of Sm-C/IGF-I on growth plate and articular chondrocytes is direct and that the effect of GH on these cells is indirect. The data further suggest that within the growth plate, the transition from reserve to proliferative status is associated with an increased Sm-C/IGF-I responsiveness, a change which may contribute to the functional differences in these cells. PMID- 2919123 TI - Noninvasive assessment of artery wall properties in children aged 4-19 years. AB - The vessel wall properties of the common carotid artery were noninvasively studied in 53 normotensive, presumed normal boys of various ages (4-19 yr) with the use of a multigate pulsed Doppler system. This device allows the on-line recording of velocity profiles and the relative changes in carotid artery diameter during the cardiac cycle. From the width of these profiles, the internal diameter of the carotid artery can be determined. With the use of internal carotid artery diameter, relative changes in carotid artery diameter during the cardiac cycle, and pulse pressure the pulse pressure, as measured in the brachial artery, the distensibility coefficient and the cross-sectional compliance were calculated. The children were allotted to three different age groups: group I (4 10 yr), group II (11-14 yr), and group III (15-19 yr). In the older children (group III) the systolic arterial pressure and the pulse pressure were significantly higher than in groups I and II. The carotid artery diameter was significantly larger and the distensibility coefficient was significantly smaller in group III than in groups I and II. The cross-sectional compliance was not significantly different in the age groups, which can be explained by the larger artery diameter in the older age group. The findings indicate that the carotid artery wall is less distensible in adolescents than in younger children. The subjects in group III showed similar carotid artery wall properties as the young adults (aged 20-34 yr) in a previous study. Therefore, it is likely that in adolescents the vascular system can be considered as mature as far as the arterial wall properties are concerned. PMID- 2919124 TI - Adrenocortical steroids in small-for-gestational-age term infants during the early neonatal period. AB - We evaluated adrenocortical steroid concentrations at birth and during postnatal adaptation (2 h until 7 days) in 10 vaginally delivered term small-for gestational-age (SGA) infants and 12 term appropriate-for-gestational age infants. Plasma aldosterone, 11-deoxycorticosterone, corticosterone, progesterone, 17-hydroxyprogesterone, 11-deoxycortisol, cortisol, and cortisone were longitudinally measured by specific RIA after Sephadex LH-20 chromatography. Mean aldosterone was significantly higher in SGA than in appropriate-for gestational-age infants (2 h to 7 days; p less than 0.001). In SGA infants, cortisone and cortisol levels were significantly lower in umbilical artery (p less than 0.05), and all glucocorticoid levels were significantly lower 12 h after birth (p less than 0.05). Thereafter (24 h to 7 days), only 11 deoxycortisol levels remained significantly lower in SGA; corticosterone and cortisol levels were even higher (p less than 0.05) in SGA 24 h after birth. The data suggest that SGA infants maintain high aldosterone levels throughout the 1st wk of life. Low cortisol and cortisone levels in umbilical artery as well as low glucocorticoid levels at 2 h and/or 12 h compared to term appropriate-for gestational-age infants may reflect either a less stressful postnatal adaptation or, more likely, a reduced adrenocortical synthesis in term SGA infants. PMID- 2919125 TI - Effects of ammonium chloride, salicylate, and carnitine on palmitic acid oxidation in rat liver slices. AB - To explore the possible association of hyperlipidemia with hyperammonemia and aspirin ingestion, the effects of NH4+, salicylate, and carnitine on the oxidation of [1-14C]palmitic acid to acid-soluble products (ASP) and to CO2 were investigated in rat liver slices. DL-carnitine (5 mM) increased total oxidation (ASP + CO2) more than oxidation to CO2. KCN (1.5 mM) inhibited more than 90% of the oxidation. NH4Cl inhibited the oxidation that reached a maximum at about 40 mM, but the inhibition of oxidation to CO2 (63%) was larger than that of total oxidation (30%). Carnitine did not influence NH4+ inhibition, which is consistent with the results reported for isolated mitochondria. Salicylate effects depended on salicylate concentration as well as on the presence of carnitine. In the absence of carnitine, inhibition of total oxidation reached 90% at 3 mM salicylate but that of oxidation to CO2 reached 50%. Velocity calculated at saturating palmitic acid concentration for total oxidation was slightly increased by 0.75 mM salicylate, but the increase for oxidation to CO2 was larger. At 3 mM salicylate, velocity at saturating palmitic acid concentration for the oxidation was decreased, but the decrease for oxidation to CO2 was smaller than for total oxidation. Carnitine partially relieved the inhibition of total oxidation and further increased the formation of CO2. The combination of 20 mM NH4Cl and 0.75 mM salicylate inhibited total oxidation, which was more than additive of the individual effects, and carnitine partially relieved the inhibition. It is concluded that NH4+ exerted a stronger inhibition of oxidation to CO2 than of oxidation to ASP, whereas salicylate strongly inhibited the oxidation to ASP but increased the oxidation to CO2 by uncoupling mitochondrial oxidative phosphorylation. Therefore, hyperammonemia and aspirin ingestion can inhibit fatty acid oxidation and mitochondrial metabolism that could lead to the pathophysiology seen in some childhood diseases such as Reye's syndrome. Carnitine therapy might offer some benefits. PMID- 2919126 TI - Vascular to alveolar leak of iron dextran (120 kD) in the immature ventilated rabbit lung. AB - Rabbit fetuses were delivered by hysterotomy on day 27 or 28 of gestation. Immediately after birth, the animals were tracheotomized and received by intravenous injection 0.2 mu Ci radiolabeled albumin and 11 mg iron dextran in 0.2 ml saline. The newborn rabbits then were ventilated artificially with a tidal vol of 12 ml/kg for 5-20 min. One group of nonventilated animals served as controls. At the end of the experiment, one lung was lavaged via the airways and the other was fixed for histologic examination. The recovery of labeled albumin and iron dextran in the lavage fluid was quantified. Iron dextran complexes were easily identified in the lung sections by staining with Prussian blue. Iron dextran accumulated in the airspaces of animals delivered on day 27 (about 4% of the injected dose during 10-20 min of ventilation). The albumin leakage was slightly higher than that of the dextran, a result consistent with different mol wt of the markers. The vol density of leaking alveoli in histologic sections increased with time, from 0 at birth to a mean value of 0.36 after 20 min of ventilation. The leakage starts as a focal event, gradually involving more and more terminal airspaces. In the histologic sections, there was no indication of a significant leakage at the bronchiolar level, although the epithelium of terminal and preterminal airways was clearly injured in all ventilated animals. PMID- 2919127 TI - Influence of increased pulmonary vascular pressures on the closure of the ductus arteriosus in newborn lambs. AB - Neonatal conditions associated with increased pulmonary artery pressure have an increased incidence of patent ductus arteriosus. We operated on 15 near term fetal lambs and placed mechanical occluders into or around both branch pulmonary arteries so that main pulmonary artery blood pressure could be controlled. The lambs were delivered and ventilated for 4 h. In seven lambs, the branch vessels were obstructed so that pulmonary artery pressure increased to equal aortic pressure; in eight lambs (control), the branch vessels were not obstructed. There were no significant differences between the two groups in circulating prostaglandin E2 or 6 keto F1 alpha concentrations, PaO2, pH, or PaCO2. Despite these similarities, ductus resistance in the lambs with elevated pulmonary pressure was significantly less than that in the control lambs. After the 4 h measurements, we studied the ductus in vitro. We have previously found that ductus arteriosus constriction produces ischemia of its muscle wall that limits its ability to dilate or constrict any further. Ductus from lambs with elevated pulmonary pressure had a significantly increased ability to respond to oxygen, prostaglandin E2, and indomethacin compared with ductus from control lambs; these findings are consistent with less ductus constriction in vivo. Thus, the high incidence of patent ductus arteriosus in neonates with elevated pulmonary vascular resistance may be due in part to the increased pulmonary vascular pressure, which opposes ductus constriction and preserves ductus responsiveness. Conversely, the normal drop in pulmonary pressure that occurs in full term infants may facilitate the closure of the ductus after delivery. PMID- 2919128 TI - In vivo mechanical properties of the developing airway. AB - The inherent mechanical characteristics of the airways are determined in part by their elastic and viscoelastic properties. As compliant structures during early development, the airways are susceptible to significant distention and collapse, depending on the proportionality between airway volume and transmural pressure. To characterize the age-related changes in airway mechanical properties, the elastic and viscoelastic behavior of in vivo tracheal segments were evaluated in preterm and newborn lambs over a wide range of developmental age (108 to 154 days postconceptional age). Tracheal pressure-vol relationships and concomitant airway compliance measurements were used to determine elastic behavior. Calculations of the tracheal relaxation time constant on the same tracheal segments were used to evaluate airway viscoelastic behavior. Data demonstrated a significant (p less than 0.01) correlation with developmental age. With increasing age, the airways were found to be less compliant, and the tracheal relaxation time constant was observed to decrease. The difference in elastic properties of the trachea, in vivo compared to in vitro, suggest that neural-humoral and surrounding connective tissue factors may affect the elasticity of the developing airway. Although the modulating effects of smooth muscle tone and supporting connective tissue assist in the control of airway dimension and resistance to airflow in the intact airway, the age-related differences in the elastic properties may be a factor that predisposes the more immature airway to positive pressure-induced damage. PMID- 2919129 TI - Abnormality of odd-numbered long-chain fatty acids in erythrocyte membrane lipids from patients with disorders of propionate metabolism. AB - In propionic acidemia and methylmalonic aciduria, disorders of propionate catabolism, excess intracellular propionyl-CoA leads to an enhanced synthesis of odd-numbered long-chain fatty acids. Red cell membrane lipids of patients with these disorders contain pentadecanoic, heptadecanoic, and heptadecenoic acids in excess of normal levels. The odd-numbered long-chain fatty acid content may reflect individual differences in severity of these disorders as well as the degree of effective dietary control. It might be a useful long term parameter for determining the effectiveness of clinical management. PMID- 2919130 TI - Galactose metabolism in human ovarian tissue. AB - Galactose metabolism was studied in human ovarian tissue obtained from 14 women controls between 21 and 72 y of age, and one 21-y-old galactosemic patient with hypergonadotrophic hypogonadism. Tissue slices were incubated with 1-14C galactose, and labeled intermediates were analyzed by anion-exchange column chromatography. Activities of enzymes related to the galactose pathway: galactokinase, transferase, epimerase, uridine diphosphoglucose (UDPGlc) and uridine diphosphogalactose pyrophosphorylases, and UDPGlc and uridine diphosphogalactose pyrophosphatases were measured in ovarian homogenates using radioisotopic, spectrophotometric, and fluorometric techniques. Incorporation of carbon label from 1-14C-galactose into various galactose and glycolytic intermediates, as well as carbon dioxide and TCA-insoluble materials was demonstrated in samples from non-galactosemic controls. In tissue from the galactosemic individual, no labeled carbon dioxide was produced and very little incorporation into TCA-insoluble material was found. Labeled galactose-1 phosphate was elevated. In normal ovarian tissue, specific activities of galactokinase, transferase, epimerase, and UDPGlc pyrophosphorylase are much higher than those found in the red cells and in testes. UDPGlc pyrophosphorylase activity is about 50 times that of transferase, suggesting that uridine nucleotide sugars have an important role in the normal development and function of the ovary. It is hypothesized that premature ovarian failure, often observed in patients with galactosemia, is due to interference with nucleotide sugar metabolism and the synthesis of galactose containing glycoproteins and glycolipids consequent to the enzymatic defect in the major pathway of galactose metabolism. PMID- 2919131 TI - 15N tracer studies of protein metabolism in low birth weight preterm infants: a comparison of 15N glycine and 15N yeast protein hydrolysate and of human milk- and formula-fed babies. AB - Nitrogen flux and protein synthesis and degradation were estimated using a single oral bolus of 15N glycine or 15N yeast protein hydrolysate and measuring the 15N enrichment of urinary ammonia in five low birth wt infants fed a low birth wt formula and in six who were receiving their own mother's breast milk. Results derived from using 15N-glycine and 15N-yeast hydrolysate tracers in a randomized crossover study in 10 studies on seven infants showed, with one exception, higher turnover rates and more interindividual variation with the 15N yeast. Both tracers showed good reproducibility in two infants who had repeated studies. Although wt gain was similar in both groups, nitrogen intake and retention were greater (p less than 0.01) in the formula-fed group. Mean nitrogen turnover was similar in both groups, but there was a greater variance in the human milk-fed group which also had a greater nitrogen turnover/U absorbed nitrogen (p less than 0.025) and a lower excretion of nitrogen/U flux. PMID- 2919132 TI - Delayed lung maturation in the macrosomic offspring of genetically determined diabetic (db/+) mice. AB - We studied a genetically determined diabetes in pregnancy, the heterozygous diabetes (db/+) mouse. We found that fetal mice from these pregnancies are macrosomic with increased body, lung, and placenta wt, have altered organ protein, DNA and phospholipid content, and exhibit abnormal carbohydrate metabolism with increased liver and glycogen content. We further studied the effect of increased substrate availability and utilization on lung growth and maturation in (db/+) fetal mice, by measuring lung phospholipid synthesis as represented by the incorporation of the radiolabeled precursors, [3H]choline and [14C]glycerol, in fetal lung at 18 days' gestation (term = 19). Diabetic fetuses incorporated significantly more [3H]choline into disaturated phosphatidylcholine than controls (1.32 +/- 0.10 X 10(-2) versus 0.78 +/- 0.05 X 10(-2) nmol/g protein/min, mean +/- SE; p less than 0.001), but significantly less [14C]glycerol into phosphatidylglycerol than controls (3.18 +/- 0.38 versus 4.91 +/- 0.53 nmol/g protein/min, mean +/- SE; p less than 0.002), and their phosphatidylglycerol/phosphatidylinositol synthesis ratios were decreased (1.81 +/- 0.18 versus 3.17 +/- 0.14; mean +/- SE; p less than 0.001). Diabetic fetal lungs appeared morphologically less mature than controls at 18 days' gestation, as shown by a significantly decreased air space density (0.27 +/- 0.01 versus 0.43 +/- 0.02, mean +/- SE; p less than 0.001) and alveolar epithelial cell/total tissue ratio (0.54 +/- 0.02 versus 0.66 +/- 0.03, mean +/- SE; p less than 0.01). The increased synthesis of lung disaturated phosphatidylcholine in diabetic fetal mice may reflect the enhancement of body and lung growth in these macrosomic fetuses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2919133 TI - Ischemia alters cerebral vascular responses to hypercapnia and acetylcholine in piglets. AB - Effects of ischemia (20 min) on cerebral cortical prostanoid synthesis and microvascular responses to hypercapnia and topical acetylcholine were examined in anesthetized newborn pigs. Pial arteriolar dilation in response to hypercapnia (10% CO2 ventilation, 10 min) was absent 2 h after ischemia and reversed toward constriction by 24 h postischemia. In sham control piglets, hypercapnia increased cortical periarachnoid fluid prostanoid concentrations. After ischemia, hypercapnia did not affect prostanoid concentrations on the brain surface. Acetylcholine (10(-3) M)-induced pial arteriolar constriction was reversed toward dilation 24 h after cerebral ischemia. Further, acetylcholine-induced prostanoid synthesis was markedly attenuated after ischemia. We conclude that cerebral ischemia-reperfusion alters cerebral prostanoid synthesis and microvascular control in newborn pigs. These abnormalities persist for at least 24 h. PMID- 2919134 TI - Human milk feeding enhances the urinary excretion of immunologic factors in low birth weight infants. AB - The effects of fortified human milk feedings on the urinary excretion of lactoferrin, lysozyme, secretory component, IgA, and secretory IgA antibodies to Escherichia coli O antigens were investigated in very low birth wt infants. Infants were maintained on either a human milk or a cow's milk preparation. The amounts of each immune factor that were ingested and excreted were quantified during balance studies conducted at 2.5 and 5 wk of age. Serum levels of these immune factors were similar in both feeding groups. The urinary excretion of all factors except lysozyme was 7- to 150-fold greater in infants fed human milk than in those fed cow's milk formula. IgA was the only factor for which the amount of the factor excreted correlated with the amount ingested. Fragments as well as whole molecules of lactoferrin were found in the urine of the infants fed human milk, but the molecular sizes of the excreted proteins exceeded those normally filtered by the kidneys. Therefore, the genesis of the enhanced levels of host defense factors in the urine of infants fed human milk is not clear. Gastrointestinal absorption and subsequent renal excretion as well as enhanced production of immune factors in the infant's urinary tract are possible explanations. PMID- 2919135 TI - Maturation of chloride-bicarbonate exchange in rat ileal brush border membrane vesicles. AB - The present studies were designed to examine the ontogeny of the Cl- -HCO3- exchange process in the ileum of suckling (2 wk old), weanling (3 wk old), and adult (6 wk old) rats using well-validated brush border membrane vesicle techniques. The purity of the vesicle preparation was verified by demonstrating that the activity of brush border marker enzyme activity was enriched 30-fold compared to the cell homogenate. Glucose uptake experiments demonstrated an overshoot phenomenon under Na+ gradient conditions, but not in the absence of Na+. Chloride uptake varied inversely with the extravesicular osmolarity, demonstrating that transport was into an osmotically sensitive space. Membrane binding accounted for only 20% of total uptake. An inwardly-directed pH gradient (pHout/pHin = 5.2/7.5) produced overshoot Cl- uptake in all age groups. The magnitude of overshoot was greatest in suckling rats and declined with advancing age. Addition of an outwardly-directed HCO3- gradient yielded further stimulation of Cl- uptake in suckling and weanling animals but could not be demonstrated in the adult. The majority of Cl- uptake proceeded via an electroneutral exchange process. However, a conductive component was present, as demonstrated by enhancement of uptake when the vesicles were rendered positive inside by a K+ gradient and valinomycin, as compared with voltage clamp conditions. At 5 mM concentration, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, an inhibitor of anion exchange, inhibited Cl- uptake by 62, 44, and 33%, respectively in suckling, weanling, and adult rats. The initial rate of uptake was linear for 8 s.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2919136 TI - Quantitative histology of cartilage cell columns in the human costochondral junction: findings in newborn and pediatric subjects. AB - The mean number of cells per cartilage column and the proportion of hypertrophic and proliferative chondrocytes per column were determined in the costochondral junction in a population of normal subjects including 10 fetal-newborns and 15 subjects aged 0.3-16 y of age. Both the mean number of cells per column and the proportion of proliferative cells per column were significantly greater in the fetal-newborn population compared to the pediatric population (12.6 +/- 1.0 versus 8.4 +/- 0.4, p less than 0.001 and 39.6 +/- 6.9 versus 24.4 +/- 2.5, p = 0.025, respectively) (mean +/- sem [n]). The number of cells per column bore a significant negative relationship to subject age (r = -0.52, p = 0.007). Significant positive correlations were found between the mean number of cells per column and age-specific growth velocity both in males (length-height velocity = [(6.3) (mean number of cells) - 44.1], r = 0.72, p = 0.02) and in females (length height velocity = [(3.4 (mean number of cells) - 14.4], r = 0.77, p = 0.006). These data will provide normative values against which abnormalities characteristic of the skeletal dysplasias can be compared. PMID- 2919137 TI - Health care of physicians' children. AB - In anecdotal reports, problems have been cited in the health care of physicians' children, but no systematic study of this issue has been attempted. Pediatricians in a community of high physician density were interviewed to determine whether and how the health care of physicians' children differs from that of children of equivalent socioeconomic status. Of the community's 33 pediatricians, 94% responded to items in a 45-minute structured interview, for which test-retest reliability was demonstrated. Systematic differences in the care of physicians' children included delayed help seeking and increased self-referral to specialists by parents, and poor documentation of psychosocial history, less detailed instruction giving, and a reluctance to discuss problem behavior by pediatricians. Reasons cited by pediatricians for these problems included inappropriate assumptions concerning the medical knowledge of the physician's family, confusion between the roles of healer and help seeker, and embarrassment about discussing personal issues with colleagues. Pediatricians and physician parents need to become aware of and communicate about the potential for problems in the health care of physicians' children. PMID- 2919138 TI - Low morbidity and mortality of status epilepticus in children. AB - In an ongoing study of status epilepticus, 193 children with status epilepticus of varying causes have been followed up for a mean period of 13.2 months. Of these, 97 patients were recruited prospectively. The patients' ages ranged from 1 month to 18 years (mean, 5.0 years). The cause of the status epilepticus was classified as idiopathic in 46 cases, remote symptomatic in 45, febrile in 46, acute symptomatic in 45, and progressive neurologic in 11. The mortality and incidence of sequelae following status epilepticus was low and primarily a function of etiology. Seven children died within 3 months of having the seizure. New neurologic deficits were found in 17 (9.1%) of the 186 survivors. All of the deaths and 15 of the 17 sequelae occurred in the 56 children with acute or progressive neurologic insults. Only two of the 137 children with other causes sustained any new deficits (P less than .001). Duration of the status epilepticus affected outcome only within the acute symptomatic group (P less than .05). Neurologic sequelae occurred in 29% of infants younger than 1 year of age, 11% of children 1 to 3 years of age, and 6% of children older than 3 years of age. However, this was a reflection of the greater incidence of acute neurologic disease in the younger age groups. Within each cause, age did not affect outcome. Of the 193 children, 61 (32%) had a history of prior unprovoked seizures. Of the 125 surviving children with no history of prior unprovoked seizures, 37 (30%) had subsequent unprovoked seizures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2919139 TI - Factors associated with surfactant treatment response in infants with severe respiratory distress syndrome. AB - In a prospective, randomized study of 18 infants treated with bovine surfactant (surfactant TA, Tokyo Tanabe Co, Tokyo) for severe respiratory distress syndrome, a lasting response was found in 12 infants (66%), a transient response was found in two (11%), and no response was found in four (22%) when arterial to alveolar PO2 ratios were used to define responses during the first 48 hours after treatment. In contrast, three of 23 control infants (13%) had a transient or lasting "response" to sham treatment (Pediatrics 1987;79:31-37). To determine whether maldistribution of surfactant could explain lack of response or a transient response, surfactant TA was mixed with technetium-99m sulfur colloid (approximately 300 mu Ci per infant), and eight infants with severe respiratory distress syndrome were treated six to 58 hours after birth. Scintigraphy of the lungs was performed three to 15 hours after treatment. Although a lasting response was observed in three infants, a transient one in three, and no response in two, no gross maldistribution of the radioactive label was found. Either lung received from 37% to 62% of the total radioactivity. During the past 3 years, in all infants with severe respiratory distress syndrome who were treated with surfactant (n = 29), poor or transient responses were associated with early patent ductus arteriosus and air leaks (pulmonary interstitial emphysema and pneumothoraces). Pathophysiologic conditions associated with respiratory distress syndrome are more likely to explain suboptimal responses after surfactant treatment than gross maldistribution of surfactant in the lungs. PMID- 2919140 TI - Is my child normal yet? Correlates of vulnerability. AB - There are some children whose parents believe them to be unusually susceptible to medical or developmental problems--"vulnerable"--despite a lack of objective evidence of any difficulty. The "vulnerable child syndrome" refers to a constellation of behaviors that are thought to develop as a result of this excessive parental anxiety and subsequent difficulties in limit setting. In this study, the sense of vulnerability expressed by mothers concerning their healthy 3 year-old children is explored; children born prematurely and with considerable neonatal morbidity are compared with children born at full-term. Sense of vulnerability is assessed through the use of a simple instrument, the use and validity of which are described. Mothers of premature infants described a significantly greater sense of vulnerability concerning their children than did mothers of full-term infants. Mothers with more education described a greater sense of vulnerability than did less well-educated mothers, although mothers who claimed greater well-being and marital satisfaction described a lesser sense of vulnerability. Mothers with a greater sense of vulnerability concerning their children also reported more behavior problems, especially in the sphere of discipline, peer relationships and self-control, and in internalizing and somatic symptoms. Pediatricians can intervene in the development of the vulnerable child syndrome by recognizing those children at special risk and helping their parents to nurture their health and independence. PMID- 2919141 TI - Pneumogram recordings in infants resuscitated for apnea of infancy. AB - Infants who sustained a spell of apnea of infancy during which they were resuscitated have been shown to be at increased risk for sudden infant death syndrome. To determine the value of the pneumogram as a predictor of outcome in this population, the first pneumogram obtained of 51 such infants was analyzed. The infants were grouped on the basis of subsequent outcome during a course of monitoring: group 1--infants who died during a subsequent event; group 2--infants who received resuscitation or vigorous stimulation to terminate a subsequent spell; group 3--infants who survived and did not have a significant subsequent episode. The results for these infants were compared with those of a control group matched for age and sex. A detailed, blinded computer analysis revealed no significant difference in the results of the pneumogram analysis between the three groups. It did not identify the infants in whom apneic spells necessitating resuscitation subsequently developed or those who died. However, when compared with the control group, infants with apnea of infancy had significantly higher mean respiratory rates, heart rates, and tachycardia indexes. It is concluded that, although the first pneumogram does not predict the risk of an adverse outcome in a population of infants with severe apnea of infancy, it does reveal subtle cardiorespiratory differences between study and control infants. PMID- 2919142 TI - Auditory brainstem responses and clinical follow-up of high-risk infants. AB - Auditory brainstem response (ABR) evaluations were performed on 667 high-risk infants from an infant special care unit. Of these infants, 82% passed the ABR. Those infants who failed the ABR were classified into two groups, those who failed at 30 dB hearing level and those who failed at 45 dB hearing level. All of the infants were encouraged to return for otologic/audiologic follow-up in 1, 3, or 6 months, depending on the initial ABR results. All of the infants with severe hearing impairments came from the group who failed at 45 dB hearing level. The incidence of severe sensorineural hearing impairment in this population was estimated to be 2.4%. For the group that failed at 30 dB hearing level, 80% of those who were abnormal at follow-up were considered to have conductive hearing disorders and 20% had mild sensorineural hearing impairments. In addition, infants enrolled in a parent-infant program for hearing impaired by 6 months of age were from the ABR program; however, several infants entered the parent-infant program at a relatively late age because they did not meet the high-risk criteria, they were from other hospitals, or they were not detected by the ABR program. PMID- 2919143 TI - Fear of obesity among adolescent girls. AB - The perceptions concerning weight, dieting practices, and nutrition of 326 adolescent girls attending an upper middle-class parochial high school were studied in relation to their body weight. Underweight or overweight students were those with greater than 10% body weight differential for height. The high school students reported an exaggerated concern with obesity regardless of their body weight or nutrition knowledge. Underweight, normal weight, and overweight girls were dieting to lose weight and reported frequent self-weighing practices. As many as 51% (n = 60) of the underweight adolescents described themselves as extremely fearful of being overweight and 36% (n = 43) were preoccupied with body fat. A distorted perception of ideal body weight was documented, particularly among the underweight students; the greater the underestimation of perceived ideal body weight, the greater the actual deficit in ideal body weight for height of the students (r = .73; P less than .001). Normal weight and overweight girls had better concordance between their actual and perceived ideal body weight for height. The frequency of bingeing and vomiting behaviors was similar among the three weight categories. The data suggest that fear of obesity and inappropriate eating behaviors are pervasive among adolescent girls regardless of body weight or nutrition knowledge. PMID- 2919144 TI - Severe retinopathy in convalescent preterm infants with mild or regressing retinopathy of prematurity. PMID- 2919145 TI - Duration of pediatric and internal medicine practice in Oregon. PMID- 2919146 TI - Status epilepticus: it's not what we've thought or taught. PMID- 2919147 TI - Children, adolescents, and television--1989: I. Television violence: a critique. PMID- 2919148 TI - Children, adolescents, and television--1989: II. The role of pediatricians. PMID- 2919149 TI - American Academy of Pediatrics Committee on Genetics: Newborn screening fact sheets. PMID- 2919151 TI - [Medical journals and editorial freedom]. PMID- 2919150 TI - Pharmaceutical and Biomedical Analysis Meeting. Groningen (The Netherlands), 11 November 1988. Abstracts. PMID- 2919152 TI - [Urinary tract infections, etiology, diagnosis and treatment with effective antibiotics]. AB - Among young, sexually active women, the prevalence of urinary tract infections (UTI) is five per cent, which is 30-50 times higher than among men. The incidence increases with age, and the female: male ratio declines. UTI account for 40 per cent of nosocomial infections. Single dose treatment is to be highly recommended in acute, uncomplicated cases of UTI in adult women, the advantages being satisfactory effect, fewer side effects, reduced development of resistance, and substantial reduction in antibiotic consumption. PMID- 2919153 TI - [Hypothyroidism in the elderly--a concealed disease]. AB - Hypothyroidism in the elderly seldom corresponds to the text-book picture of this disorder. Symptoms and signs develop insidiously, and may easily be taken for the result of arteriosclerotic disease. Screening for hypothyroidism in elderly people is advocated, and serum-TSH is recommended as the primary investigation for such screening. Substitution with thyroxine must be started cautiously and with very small doses. Healthy people with subclinical hypothyroidism should be observed for the possible occurrence of symptoms and signs. PMID- 2919154 TI - [Nerve growth factor (NGF)--the current state of knowledge]. AB - As Nerve Growth Factor (NGF) is probably the growth factor most extensively studied so far, it serve as a model of other growth factors. NGF regulates the survival of specific populations of neurons during critical periods of their development. NGF is also essential to the development and maintenance of specific functional properties of these neurons and to the ability of certain neurons to regenerate. PMID- 2919155 TI - [The Danop Data System for decentralized postoperative surveillance of wound infections]. AB - The Danop Data System is a microcomputer system designed for the local (ward) surveillance of postoperative surgical infections. The system is served by a simply operated microcomputer program capable of tabulating data input in four standard tables providing continuous information sufficient for surveillance purposes. The aim is that, within a five-year period, 50 per cent of all Danish hospitals will adopt this or similar systems. The system is envisaged as a preliminary to more systematic surveillance of all nosocomial infections. PMID- 2919156 TI - [Clinical chemical parameters for metabolic control of patients with diabetes mellitus]. AB - Fructosamine and various measures of blood glucose were compared to glycosylated hemoglobin as indices of glycaemic control in 148 patients with insulin treated diabetes. Fructosamine correlated fairly well with glycosylated hemoglobin (r = 0.67), but around 40 per cent of the patients with glycosylated hemoglobin below upper reference limit had a fructosamine value over upper reference limit and vice versa. The possibility to predict the level of glycosylated hemoglobin from fasting blood glucose, postprandial blood glucose, and self-measured blood glucose was poor. The difference in self-measured blood glucose from patients with high versus low levels of glycosylated hemoglobin was very modest (0.5-2.0 mmol/l). It is concluded that it is reasonable to measure both glycosylated hemoglobin and fructosamine to evaluate glycaemic control in insulin treated diabetic patients. Fasting blood glucose, postprandial blood glucose, and self measured blood glucose only seem to reflect glycaemic control to a minor degree. PMID- 2919157 TI - [Bronchoscopy in monosymptomatic hemoptysis--hemoptysis in bronchial carcinoma]. AB - Blood in sputum, haemoptysis, is a common symptom in mucous membrane disorders of the respiratory tract--it is often seen in conjunction with inflammation but may also be associated with malignant tumours of the respiratory tract. In a survey of 422 patients with monosymptomatic haemoptysis, 15 patients with bronchogenic carcinoma were identified. A cytological examination of the sputum of these 15 patients was carried out, and in 9 of these cases suspected malignant cells were observed. From these and other observations it is concluded that with patients of over 40 years of age who are smokers with haemoptysis, but who display a normal X ray examination of the thorax, it would be prudent to carry out a cytological examination of the sputum before bronchoscopy. PMID- 2919158 TI - [Nonparametric correlation analysis]. PMID- 2919159 TI - [Health for all by the year 2000: human rights and health]. AB - Human rights, humanitarianism, and equality in health and access to care are some of the cornerstones of the European Health For All (HFA) programme. The World Health Organization has set a target of reducing present national and international differences in health status by 25 per cent. This may well be an Utopian dream, in view of the gulf that exists between different socio-economic categories with regard to lifespan, and infant mortality and morbidity. An additional source of concern is the lack of political initiative to resolve these problems. PMID- 2919160 TI - [Health hazards from radiation from broadcasting equipment]. PMID- 2919161 TI - Model of the interactions of calichemicin gamma 1 with a DNA fragment from pBR322. AB - An analysis of the binding interactions of several DNA-drug complexes that utilize carbohydrates for DNA recognition has been undertaken. It is proposed that the carbohydrate residues function as general minor groove binding elements, and the stereochemistry of aglycone attachment sites is generally disposed to promote a right-handed helical geometry that is complementary to right-handed DNA. The constitution and stereochemistry of the DNA double-strand cleaving agent calichemicin gamma 1 is consistent with this analysis. Docking experiments with computer-generated models of this drug and a dodecamer duplex that was found to serve as a calichemicin cleavage site were performed to gain insight into the origin of the drug's sequence-selective binding and cutting properties. A model is presented that provides a molecular level understanding of the double-strand cleavage patterns that result from the action of calichemicin gamma 1 on DNA. PMID- 2919162 TI - Separate cis-regulatory elements confer expression of phosphoenolpyruvate carboxykinase (GTP) gene in different cell lines. AB - The gene encoding cytosolic phosphoenolpyruvate carboxykinase (GTP) [PEPCK; GTP:oxaloacetate carboxy-lyase (transphosphorylating), EC 4.1.1.32], a key enzyme in gluconeogenesis and glyceroneogenesis, is expressed in tissues that arise from different embryonal origins: the gluconeogenic liver arises from endoderm, whereas the gluconeogenic kidney cortex and glyceroneogenic adipose tissue arise from the mesoderm. To identify the cis-regulatory elements conferring the differential gene expression, PEPCK chimeric genes were transfected into two rat hepatoma cell lines (H4IIEC3 and HTC-M1.1) and mouse adipocytes (3T3F442A), which express the endogenous gene, and into myoblasts and preadipocytes, which do not express it. The results demonstrate that 597 base pairs of the 5' flanking region of the PEPCK gene are sufficient to confer cell-specific gene expression in the PEPCK-expressing hepatoma cells and adipocytes. However, different elements within this 597-base-pair region enhance the gene expression in the hepatoma cells (endoderm) and adipocytes (mesoderm). In the hepatocytes, expression is conferred by two elements--one 5' of position -362 and the other 3' of position 98 with respect to the transcription start site. The region in between these two elements (from -362 to -98), which seems to inhibit the gene expression in the hepatocytes, confers enhanced expression in the adipocytes. Moreover, the distal positive regulatory element of the hepatocytes seems to be orientation and PEPCK promoter dependent. In contrast, the positive regulatory element of the adipocytes seems to act as a more typical enhancer. These results suggest that separate cis-regulatory elements confer cell-specific expression of the PEPCK gene. PMID- 2919163 TI - Binding of hormone accelerates the kinetics of glucocorticoid and progesterone receptor binding to DNA. AB - Steroid hormone receptors induce genes by virtue of their interaction with DNA regulatory sequences. The hormonal response of a particular gene in vivo correlates with binding of the hormone to the receptor and supposedly reflects the degree of occupancy of the corresponding DNA regulatory sequences. However, in vitro the steroid-free glucocorticoid and progesterone receptors bind specifically to the regulatory sequences of mouse mammary tumor virus, thus raising questions on the role of the hormone in DNA binding in vivo. By using monoclonal antibodies, gel retardation assays, and filter binding techniques we show here that binding of a functional steroid to either the glucocorticoid or the progesterone receptors influences the kinetics of the protein-DNA interaction in vitro. In the presence of hormone the on rate of receptor binding to DNA fragments with or without regulatory sequences is accelerated 2- to 5-fold, and the off rate is accelerated 10- to 20-fold. The receptors complexed to an antihormone bind to DNA with kinetics intermediate between those of the steroid free and the hormone-bound protein. Thus, ligand binding accelerates the kinetics of receptor binding to DNA and this could partly account for the behavior of the hormone receptor observed in vivo. PMID- 2919164 TI - Regulation of the low density lipoprotein receptor and hydroxymethylglutaryl coenzyme A reductase genes by protein kinase C and a putative negative regulatory protein. AB - Transcription of the low density lipoprotein receptor (LDL-R) and 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase genes was rapidly and transiently induced (8.5- and 2.3-fold, respectively) early during phorbol 12-myristate 13 acetate (PMA)-induced macrophage differentiation of the human monocytic leukemia cell line THP-1. The levels of mRNA coding for LDL-R and HMG-CoA reductase increased soon after induction, reached a maximum (12- and 7-fold increase, respectively) in 2-3 hr, and then rapidly returned to the low constitutive levels observed before induction. The stability of LDL-R mRNA did not change significantly during differentiation, whereas that of HMG-CoA reductase mRNA decreased by about 5-fold 6 hr after the addition of PMA. Transcriptional induction of both LDL-R and HMG-CoA reductase genes (5.6- and 2-fold, respectively) was also observed when undifferentiated cells were treated with cycloheximide (CHX), resulting in a transient increase in steady-state mRNA (7- and 3-fold, respectively). These results suggest that expression of the two genes is maintained at low constitutive levels in uninduced THP-1 cells by a protein with a short half-life. Superinduction of both genes occurred when PMA and CHX were added simultaneously. The induction of LDL-R and HMG-CoA reductase mRNAs during early macrophage differentiation is mediated by protein kinase C. It is hypothesized that protein kinase C acts directly or indirectly to inactivate the labile negative regulatory protein. Induction of LDL-R mRNA was also observed when the human hepatocarcinoma cell line Hep G2 was treated with PMA and CHX, suggesting that this mechanism of regulation may exist in several cell types. PMID- 2919165 TI - UV-induced DNA-binding proteins in human cells. AB - To investigate the response of human cells to DNA-damaging agents such as UV irradiation, we examined nuclear protein extracts of UV-irradiated HeLa cells for the presence of DNA-binding proteins. Electrophoretically separated proteins were transferred to a nitrocellulose filter that was subsequently immersed in a binding solution containing radioactively labeled DNA probes. Several DNA-binding proteins were induced in HeLa cells after UV irradiation. These included proteins that bind predominantly double-stranded DNA and proteins that bind both double stranded and single-stranded DNA. The binding proteins were induced in a dose dependent manner by UV light. Following a dose of 12 J/m2, the binding proteins in the nuclear extracts increased over time to a peak in the range of 18 hr after irradiation. Experiments with metabolic inhibitors (cycloheximide and actinomycin D) revealed that de novo synthesis of these proteins is not required for induction of the binding activities, suggesting that the induction is mediated by protein modification. PMID- 2919166 TI - Transcription-based amplification system and detection of amplified human immunodeficiency virus type 1 with a bead-based sandwich hybridization format. AB - The in vitro amplification of biologically important nucleic acids has proceeded principally by a strategy of DNA replication. Polymerase chain reaction was the first such protocol to achieve this goal. In this report, a transcription-based amplification system (TAS) is described. Each cycle of the TAS is composed of two steps. The first is a cDNA synthesis step that produces one copy of a double stranded DNA template for each copy of RNA or DNA target nucleic acid. During the course of this cDNA synthesis step, a sequence recognized by a DNA-dependent RNA polymerase is inserted into the cDNA copy of the target sequence to be amplified. The second step is the amplification of the target sequence by the transcription of the cDNA template into multiple copies of RNA. This procedure has been applied to the detection of human immunodeficiency virus type 1 (HIV-1)-infected cells. After four cycles of TAS, the amplification of the vif region of the HIV-1 RNA genome was measured to be, on the average, 38- to 47-fold per cycle, resulting in a 2-5 x 10(6)-fold increase in the copy number of the original target sequence. This amplification by the TAS protocol allows the detection of fewer than one HIV 1-infected CEM cell in a population of 10(6) uninfected CEM cells. Detection of the TAS-generated RNA from HIV-1-infected cells can easily be accomplished by means of a bead-based sandwich hybridization protocol, which provides additional specificity for the identification of the amplified HIV-1-specific sequence. PMID- 2919167 TI - Identifying protein-binding sites from unaligned DNA fragments. AB - The ability to determine important features within DNA sequences from the sequences alone is becoming essential as large-scale sequencing projects are being undertaken. We present a method that can be applied to the problem of identifying the recognition pattern for a DNA-binding protein given only a collection of sequenced DNA fragments, each known to contain somewhere within it a binding site for that protein. Information about the position or orientation of the binding sites within those fragments is not needed. The method compares the "information content" of a large number of possible binding site alignments to arrive at a matrix representation of the binding site pattern. The specificity of the protein is represented as a matrix, rather than a consensus sequence, allowing patterns that are typical of regulatory protein-binding sites to be identified. The reliability of the method improves as the number of sequences increases, but the time required increases only linearly with the number of sequences. An example, using known cAMP receptor protein-binding sites, illustrates the method. PMID- 2919168 TI - Cooperative interaction of Agrobacterium VirE2 protein with single-stranded DNA: implications for the T-DNA transfer process. AB - Induction of Agrobacterium tumefaciens vir gene expression by wounded plant cells results in production of a free transferable single-stranded (ss) copy of T-DNA, the T-strand. One of the Vir proteins, the VirE2 polypeptide, is a ssDNA-binding protein. In the present work, interaction of nopaline-specific VirE2 protein (Mr 69,000) with ssDNA was studied by using nitrocellulose filter binding, gel retardation, and electron microscopy techniques. The VirE2 protein was found to bind to ssDNA molecules with strong cooperativity, forming VirE2-ssDNA complexes with a binding site of 28-30 nucleotides. The VirE2-ssDNA complexes are stable at high salt concentrations and resistant to exonucleolytic activity. When examined under the electron microscope, the VirE2 protein converted collapsed free ssDNA molecules into unfolded and extended structures. The structure and properties of VirE2-ssDNA complexes predict possible functions in Agrobacterium virulence to (i) protect the T-strands from cellular nucleases and (ii) facilitate transfer of the T-strands through bacterial membranes possibly by specific interaction with putative membrane pores formed in plant-induced Agrobacterium cells. PMID- 2919169 TI - Rapid activation by interferon alpha of a latent DNA-binding protein present in the cytoplasm of untreated cells. AB - The highly conserved interferon (IFN)-stimulated regulatory elements of the human genes 6-16 and 9-27 bind to one or more proteins (E factor) detected in extracts of human Bristol 8 B cells or human foreskin fibroblast cells treated with IFN alpha. E factor is not detectable in extracts of untreated cells and appears in IFN-treated cells within less than 1 min in a form extractable with low salt and thus presumably not bound to DNA. After a few more minutes, the level of this form decreases in parallel with the increase of a form extractable only with high salt and thus presumably bound to DNA. Induction of E factor by IFN-alpha can occur in nuclei-free cytoplasts, whereas no E factor was detected in IFN-treated nucleoplasts. Together, these results suggest a model for signal transduction in which latent E factor, located in the cytoplasm, is activated or released from an inhibitor very rapidly upon binding of IFN-alpha to its receptor. Active E factor can then migrate to the nucleus, where it binds to the IFN-stimulated regulatory elements of IFN-regulated genes, activating their transcription. PMID- 2919170 TI - Estrogen-responsive element of the human pS2 gene is an imperfectly palindromic sequence. AB - Using chimeric recombinants transfected into HeLa cells and a transient expression assay, we demonstrate that the 5'-flanking region of the pS2 gene from position -428 to position -324 exhibits both constitutive and estrogen-inducible enhancer activity. The estrogen-inducible activity, but not the constitutive activity, was inhibited by antiestrogens. ICI 164,384 behaved as a pure antagonist, whereas hydroxytamoxifen was a partial agonist-antagonist. The estrogen-responsive element of the pS2 gene has been narrowed down by site directed deletion mutagenesis to a 13-base-pair (position -405 to position -393) imperfectly palindromic sequence, which in isolation can confer estrogen inducibility to the heterologous rabbit beta-globin gene promoter. On the other hand, the sequences responsible for the constitutive enhancer activity are spread over the entire region. PMID- 2919171 TI - Dynamic Monte Carlo study of the folding of a six-stranded Greek key globular protein. AB - To help elucidate the general rules of equilibrium globular protein folding, dynamic Monte Carlo simulations of a model beta-barrel globular protein having the six-stranded Greek key motif characteristic of real globular proteins were undertaken. The model protein possesses a typical beta-barrel amino acid sequence; however, all residues of a given type (e.g. hydrophobic residues) are identical. Even in the absence of site-specific interactions, starting from a high-temperature denatured state, these models undergo an all-or-none transition to a structurally unique six-stranded beta-barrel. These simulations suggest that the general rules of globular protein folding are rather robust in that the overall tertiary structure is determined by the general pattern of hydrophobic, hydrophilic, and turn-type residues, with site-specific interactions mainly involved in structural fine tuning of a given topology. Finally, these studies suggest that loops may play an important role in producing a unique native state. Depending on the stability of the native conformation of the long loop in the Greek key, the conformational transition can be described by a two-state, three state, or even larger number of multiple equilibrium states model. PMID- 2919172 TI - Primary structure of cucumber (Cucumis sativus) ascorbate oxidase deduced from cDNA sequence: homology with blue copper proteins and tissue-specific expression. AB - cDNA clones for ascorbate oxidase were isolated from a cDNA library made from cucumber (Cucumis sativus) fruit mRNA. The library was screened with synthetic oligonucleotides that encode the NH2-terminal sequence of this enzyme. Nucleotide sequence analysis of the cloned cDNA inserts revealed a 1761-base-pair open reading frame that encoded an NH2-terminal signal peptide of 33 amino acids and a mature enzyme of 554 amino acids (Mr, 62,258). The amino acid sequence deduced from nucleotide sequence analysis agrees with the NH2-terminal amino acid sequence of the purified ascorbate oxidase, as determined by microsequencing methods. Cucumber ascorbate oxidase contained four histidine-rich regions with striking sequence homology to the corresponding parts of the other multicopper oxidases such as Neurospora crassa laccase and human ceruloplasmin and, to some extent, to a low molecular weight copper protein such as plastocyanin. Moreover, these data further support the hypothesis that the small blue copper proteins and the multicopper oxidases have evolved from the same ancestral gene. By RNA blot hybridization analysis, the mRNA for the ascorbate oxidase was found to be abundant in cucumber fruit tissue while expressed at very low levels in leaf and root tissues. PMID- 2919173 TI - Distinctive traits of normal and tumor-derived human mammary epithelial cells expressed in a medium that supports long-term growth of both cell types. AB - A medium is described that supports long-term growth in culture of human primary mammary tumor cells, of normal epithelial cells from mammoplasty, and of mammary tumor cell lines. Tumor cells are shown to be distinguishable from normal mammary epithelial cells by morphology, by growth requirements, and by two markers: preferential expression of the HMFG-2 epitope on tumor cells and preferential retention in tumor cell mitochondria of the lipophilic fluorescent dye rhodamine 123. Differential fluorescence of HMFG-2 fluorescein-conjugated antibodies can be used as a basis for separation of normal and tumor cells in a fluorescence activated cell sorter, as can differential retention of rhodamine 123. PMID- 2919174 TI - Fourier analysis of cell motility: correlation of motility with metastatic potential. AB - We report the development of a computerized, mathematical system for quantitating the various types of cell motility. This Fourier analysis method simultaneously quantifies for individual cells (i) temporal changes in cell shape represented by cell ruffling, undulation, and pseudopodal extension, (ii) cell translation, and (iii) average cell size and shape. This spatial-temporal Fourier analysis was tested on a series of well-characterized animal tumor cell lines of rat prostatic cancer to study in a quantitative manner the correlation of cell motility with increasing in vivo metastatic potential. Fourier motility coefficients measuring pseudopodal extension correlated best with metastatic potential in the cell lines studied. This study demonstrated that Fourier analysis provides quantitative measurement of cell motility that may be applied to the study of biological processes. This analysis should aid in the study of the motility of individual cells in various areas of cellular and tumor biology. PMID- 2919175 TI - Targeting of a chromosomal protein to the nucleus and to lampbrush chromosome loops. AB - We have isolated a cDNA clone (SE5A) that encodes a protein on lampbrush chromosome loops of the newt Notophthalmus. In vitro-synthesized transcripts of this clone were injected into Xenopus oocytes, where they were efficiently translated. Most of the translated protein was imported into the oocyte nucleus, and some of it appeared on the chromosome loops. The translation product must contain information that permits its appropriate targeting first to the nucleus and then to the chromosome loops. PMID- 2919176 TI - Divergent evolution of part of the involucrin gene in the hominoids: unique intragenic duplications in the gorilla and human. AB - The gene for involucrin, an epidermal protein, has been remodeled in the higher primates. Most of the coding region of the human gene consists of a modern segment of repeats derived from a 10-codon sequence present in the ancestral segment of the gene. The modern segment can be divided into early, middle, and late regions. We report here the nucleotide sequence of three alleles of the gorilla involucrin gene. Each possesses a modern segment homologous to that of the human and consisting of 10-codon repeats. The early and middle regions are similar to the corresponding regions of the human allele and are nearly identical among the different gorilla alleles. The late region consists of recent duplications whose pattern is unique in each of the gorilla alleles and in the human allele. The early region is located in what is now the 3' third of the modern segment, and the late, polymorphic region is located in what is now the 5' third. Therefore, as the modern segment expanded during evolution, its 3' end became stabilized, and continuing duplications became confined to its 5' end. The expansion of the involucrin coding region, which began long before the separation of the gorilla and human, has continued in both species after their separation. PMID- 2919177 TI - Recovery of induced mutations for X chromosome-linked muscular dystrophy in mice. AB - We have used elevated levels of plasma creatine phosphokinase activity to identify muscular dystrophy phenotypes in mice and to screen the progeny of chemical mutagen-treated male mice for X chromosome-linked muscular dystrophy mutations. We were not successful in identifying heterozygous carriers of these induced muscular dystrophy mutations in greater than 8000 progeny. However, we were highly successful in identifying three additional alleles of the characterized mdx locus. These alleles of mdx were recovered from various mutagen treated males and they occur on an X chromosome that carries flanking markers that allow us to follow the mutations in genetic crosses and in the development of corresponding mutant stocks. These alleles have been designated as mdx2Cv, mdx3Cv, and mdx4Cv. Preliminary data show that mice with mdx2Cv and mdx3Cv mutations have muscular dystrophic phenotypes that do not grossly differ from the characterized mdx mutation. These additional mdx mutations expand the value of mouse models of X chromosome-linked muscular dystrophy and potentially define additional sites of mutation that impair dystrophin expression. PMID- 2919178 TI - Rapid detection of ultraviolet-induced reversion of an amber mutation in mouse L cells. AB - An amber codon (TAG) was introduced into the N-terminal coding region of the murine H-2Kb gene. The mutant gene was transfected into mouse L cells, and a clone containing a single unrearranged chromosomally integrated copy of the mutant gene was mutagenized with 254-nm UV radiation. Surviving cells were scored for surface expression of H-2Kb protein with in situ immunoperoxidase staining. Revertants were detected at a frequency of 3 X 10(-6) at a dose of 40 J/m2 (3-5% survival). Revertant genes, cloned by plasmid rescue, contained the expected thymine-to-cytosine transitions at the amber codon. These data show that revertants can be rapidly detected in mammalian cells without selection and provide a basis for the development of mammalian cell lines that could be used to study mutational phenomena. During this study the steady-state level of mRNA was reduced in L cells carrying the amber mutant H-2Kb gene compared with L cells containing a wild-type or revertant H-2Kb gene. This reduction was shown not to be due to transcriptional differences, suggesting that the amber mutation decreases stability of the H-2Kb mRNA. PMID- 2919179 TI - Chromosomes of older humans are more prone to aminopterine-induced breakage. AB - We have adopted a simplified version of the "cell hybrid cotransfer method" to test the hypothesis that human lymphocytes derived from elderly individuals have a higher chromosome instability. Peripheral blood lymphocytes from "old" male individuals and "young" controls were fused with a Chinese hamster cell line (CHO YH21), yielding 10 HAT-resistant rodent-human clones from the old propositi and 22 from the young controls (HAT = hypoxanthine/aminopterin/thymidine). Both series of hybrid clones were analyzed with respect to the retention of the enzyme glucose-6-phosphate dehydrogenase and the surface antigen MIC2 identified by monoclonal antibody 12E7, two human X chromosome-linked markers located at opposite ends of the X chromosome. Cell hybrid clones with an X chromosome from a young control retained both markers in about 70% of the cells. In contrast, cell hybrid clones with an X chromosome from an old donor retained the MIC2 marker in only 30% of their cells. Slot-blot hybridization studies have established that the observed loss of the MIC2 marker is due to loss of the coding gene, not to suppression of its expression. Similar hybridization studies with molecular probes specific for other regions of the X chromosome suggest preferential chromosomal breakage sites. T lymphocytes from old donors were also found to have an LD50 for aminopterine significantly lower than the concentration of this drug in the HAT medium used to grow the hybrids, suggesting that the higher level of gene loss observed in the X chromosomes from old donors may be directly related to their increased sensitivity to the clastogenic effect of aminopterine. We speculate that the higher rate of chromosomal breakage and of marker loss observed along the "old-age" X chromosomes could be the result of "molecular scars" accumulated with aging at sites of constitutive chromosomal fragility. PMID- 2919180 TI - Anomalous and selective DNA mutations of the Old World monkey alpha-globin genes. AB - It has been a widely accepted hypothesis that the molecular clock slows down during evolution of higher primates. By molecular cloning and nucleotide sequence comparison of a rhesus macaque alpha-globin gene to its homologs in man, orangutan, olive baboon, and other mammals, we demonstrate a burst of evolution of the baboon alpha-globin gene since its separation from the rhesus macaque. This mutation burst has occurred only at the nonsynonymous sites but not the synonymous sites. Its magnitude is at least 10-fold higher than the synonymous substitution rates in higher primates and as high as the synonymous substitution rates of the rodent lineage. On the contrary, the rate of synonymous site substitutions in the alpha-globin genes of either the rhesus macaque or the olive baboon is several times slower than that of human. Our data demonstrate an anomalous exception to the slow rates of molecular evolution in higher primates and provide strong evidence for a recently accelerated evolution of a primate globin gene under an as yet unknown selective force(s). PMID- 2919181 TI - Conservation of structural and functional domains in complement component C3 of Xenopus and mammals. AB - The cDNA sequence and the deduced amino acid sequence of the Mr 34,000 C-terminal fragment of Xenopus laevis complement component C3 are presented. The sequence of Xenopus C3 has 57% nucleotide identity to the corresponding sequence of human C3 and approximately 49% amino acid identity to C3 from human, mouse, and rabbit. The Xenopus C3 sequence shows clusters of high and of low similarity to the mammalian C3 sequences. One of these regions of high similarity represents the domain of mammalian C3b involved in the binding of properdin, a regulator of the alternative pathway of complement activation. It is not clear whether the other highly conserved regions are involved in binding to other C3 ligands. The Xenopus C3 sequence completely lacks the Arg-Gly-Asp sequence, which has been suggested to be the recognition site of the human complement receptor type 3 on the iC3b fragment of human C3. The Xenopus C3 gene is shown not to be linked to the Xenopus major histocompatibility complex, as is also the case in mammals. Since the gene of the related molecule C4 is MHC-linked in both mammals and Xenopus, the C3 and C4 genes may have separated before Xenopus and mammals speciated. PMID- 2919182 TI - Sulfation of tyrosine residues increases activity of the fourth component of complement. AB - Sulfation of tyrosine residues recently has been recognized as a biosynthetic modification of many plasma proteins and other secretory proteins. Effects of this site-specific modification on protein function are not known, but the activity of several peptides such as cholecystokinin is greatly augmented by sulfation. Here, we examine the role of sulfation in the processing and activity of C4 (the fourth component of complement), one of the few proteins in which sites and stoichiometry of tyrosine sulfation have been characterized. Our results, with C4 as a paradigm, suggest that sulfation of tyrosine residues can have major effects on the activity of proteins participating in protein-protein interactions. Sulfation of C4 synthesized by Hep G2 cells was blocked by incubating the cells with NaClO3 and guaiacol. These sulfation inhibitors did not alter secretion or other steps in the processing of C4. However, hemolytic activity of C4 was decreased more than 50%. The inhibitors' effect on C4 activity was prevented by adding Na2SO4 to restore sulfation of C4. Activity of C3, a complement component homologous to C4 but lacking tyrosine sulfate residues, was minimally reduced (19%) by the inhibitors. Decreased hemolytic activity of nonsulfated C4 apparently resulted from impaired interaction with complement subcomponent C1s (EC 3.4.21.42), the protease that physiologically activates C4. Purified C1s was able to cleave nonsulfated C4, but approximately 10-fold higher concentrations of C1s were required for that cleavage than to yield equivalent cleavage of sulfated C4. Our results suggest that activation of C4, a central component in the classical pathway of complement activation, is influenced by the level of sulfation of the protein. Thus, sulfation of C4 provides a potential locus for physiological or pharmacological modulation of complement-mediated opsonization and inflammation. PMID- 2919183 TI - Mature human eosinophils have the capacity to express HLA-DR. AB - Human eosinophils are known to lose Ia antigen expression as they mature, and, accordingly, eosinophils obtained from the blood of five eosinophilic donors and three of four normal donors failed to display the major histocompatibility complex class II antigen HLA-DR, as determined by flow cytometry. However, when eosinophils from these nine donors were maintained in culture with recombinant human granulocyte-macrophage colony-stimulating factor and murine 3T3 fibroblasts, HLA-DR consistently developed on the eosinophils. By days 4-6 of culture, 24-97% of eosinophils were HLA-DR+, and the eosinophils remained morphologically mature. In contrast, another class II antigen, HLA-DQ, was not detectable by flow cytometry on eosinophils from eight of nine donors. Cultured eosinophils were able to synthesize HLA-DR, as documented by the incorporation of [35S]methionine into immunoprecipitable HLA-DR heavy and light chains. These findings show that mature eosinophils can synthesize and express HLA-DR and provide a means whereby eosinophils may interact with CD4+ lymphocytes. PMID- 2919184 TI - Hippocampal specialization of food-storing birds. AB - In a study of 52 individuals belonging to 35 species or subspecies of passerine birds it was shown that the volume of the hippocampal complex relative to brain and body size is significantly larger in species that store food than in species that do not. Retrieval of stored food relies on an accurate and long-lasting spatial memory, and hippocampal damage disrupts memory for storage sites. The results suggest, therefore, that food-storing species of passerines have an enlarged hippocampal complex as a specialization associated with the use of a specialized memory capacity. Other life-history variables were examined and found not to be correlated with hippocampal volume. PMID- 2919185 TI - Dopamine turnover and glutathione oxidation: implications for Parkinson disease. AB - Parkinson disease is characterized by a major loss (approximately 80% or more) of dopaminergic nigrostriatal neurons and by an increased turnover of neurotransmitter by surviving neurons of the nigrostriatal tract. In theory, increased turnover of dopamine should be associated with an oxidative stress derived from increased production of hydrogen peroxide. The peroxide is formed during the oxidative deamination of dopamine by monoamine oxidase. In experiments with mice, increased presynaptic turnover of dopamine was evoked by injection of reserpine, which interferes with the storage of dopamine in synaptic vesicles. Loss of dopamine and formation of deaminated metabolites were accompanied by a significant rise (87.8%) in the level of oxidized glutathione in brain. This change was observed in the striatum, which is richly innervated by dopamine terminals, but not in the frontal cortex, which receives a much sparser innervation by catecholamine nerve terminals. The rise in oxidized glutathione was seen even though dopamine terminals constitute only 1% or less of the mass of the striatum. Clorgyline, an inhibitor of monoamine oxidase type A, blocked the formation of oxidized glutathione. These observations confirm that a selective increase in neurotransmitter turnover within nigrostriatal nerve terminals can evoke a change in cellular redox status. We suggest that an oxidative stress may play a role in the natural history of Parkinson disease. PMID- 2919188 TI - Retinoids. PMID- 2919186 TI - Trigeminovascular fibers increase blood flow in cortical gray matter by axon reflex-like mechanisms during acute severe hypertension or seizures. AB - Cerebral blood flow was measured and compared in 10 symmetrical brain regions following unilateral trigeminal ganglionectomy (n = 13), sham operation (n = 6), or trigeminal root section (rhizotomy) (n = 8) in cats. Multiple determinations were obtained in anesthetized and paralyzed animals using radiolabeled microspheres during (i) normocapnia-normotension, (ii) hypercapnia (5% CO2/95% room air), (iii) angiotensin-induced acute severe hypertension (190 greater than mean arterial blood pressure less than 210 mmHg), or (iv) bicuculline-induced seizures. Flow was symmetrical in all brain regions at rest and during increases induced by hypercapnia in the three groups. During severe hypertension or seizures, marked elevations developed bilaterally (approximately 93% and approximately 130%, respectively). In ganglionectomized animals, increases due to hypertension or seizures were attenuated by 28-32% on the denervated side within cortical gray matter regions corresponding to the anterior, middle, and posterior cerebral arteries. Flow was symmetrical within all brain regions in sham-operated animals and in the rhizotomy group, despite comparable increases in regional cerebral blood flow induced by angiotensin. Hence, the trigeminal nerve mediates blood flow adaptations during severe hypertension and seizures. Furthermore, since trigeminal cell bodies and peripheral axons are destroyed or degenerate following ganglionectomy but not following rhizotomy, local "axon reflex-like" mechanisms mediate these increases in cerebral blood flow. PMID- 2919187 TI - The two subunits of the human asialoglycoprotein receptor have different fates when expressed alone in fibroblasts. AB - Two related polypeptides, H1 and H2, comprise the human asialoglycoprotein receptor (ASGP-R). Stable lines of murine NIH 3T3 fibroblasts expressing H1 alone or H2 alone do not bind or internalize the ligand asialoorosomucoid (ASOR), which contains triantennary oligosaccharides. In contrast, cells expressing H1 and H2 together bind and degrade ASOR with properties indistinguishable from those of the ASGP-R in human hepatoma HepG2 cells. Whether or not H2 is coexpressed, H1 is synthesized as a 40-kDa precursor bearing high-mannose oligosaccharides, processed to its mature 46-kDa form, and transported to the cell surface. In cells expressing only H1, homodimers and -trimers of H1 are formed. In contrast, when expressed in 3T3 cells without H1, H2 is synthesized as its 43-kDa precursor, bearing high-mannose oligosaccharides, but is rapidly degraded. When H1 and H2 are coexpressed in the same cell, the H1 polypeptide "rescues" the H2 polypeptide; H2 is processed to its characteristic 50-kDa mature form and is transported to the surface. We conclude that the human ASGP-R is a multichain heterooligomer, probably a trimer of H1 molecules in noncovalent association with one, two, or three H2 molecules, and that the two polypeptides normally interact early in biosynthesis. PMID- 2919189 TI - Intrasession and intersession reliability of hand-held dynamometer measurements taken on brain-damaged patients. AB - Recent reports have characterized force measurements obtained with hand-held dynamometers from brain-damaged patients as being highly reliable. The purposes of this two-part study were to replicate essential parts of those studies and to further examine the reliability of these measurements in a clinical context. Repeated force measurements were taken from the nonparetic and paretic limbs of brain-damaged patients during the same testing session (Part 1) and during two testing sessions separated by two days (Part 2). The intratester intraclass correlation coefficients (ICCs) for all measurements taken during a single session ranged from .88 to .98. The ICCs for repeated measurements taken two days apart from the paretic limbs ranged from .90 to .98. The ICCs for repeated measurements taken two days apart from the nonparetic limbs ranged from .31 to .93. The ICCs for repeated measurements taken two days apart from the combined data for all limbs ranged from .79 to .97. Hand-held dynamometer measurements taken on brain-damaged patients appear to be highly reliable when taken during the same testing session. When repeated measurements are separated by a longer time interval, the measurements taken from the paretic limbs continue to be highly reliable, whereas most measurements taken on the nonparetic limbs exhibit poor reliability. PMID- 2919190 TI - Effects of unilateral brain damage on contralateral and ipsilateral upper extremity function in hemiplegia. AB - This article describes the long-term effects of unilateral penetrating hemispheric lesions on contralateral and ipsilateral upper extremity motor performance and functional outcome. Activities-of-daily-living skill and gross motor performance contralateral to the lesions were compared among 32 left-sided and 19 right-sided hemiplegic subjects using analysis of variance and chi-square techniques. Ipsilateral to the damaged hemisphere, fine motor tasks of simple visual motor reaction time, grip and pinch strength, finger tapping, and Purdue Pegboard performance were tested. Analysis of covariance compared each ipsilateral task to performance in the corresponding hand of 70 matched controls. Results indicate similar long-term functional ADL outcome in right and left hemisphere-damaged subjects, despite more severe contralateral functional motor deficits following lesions of the left hemisphere. Right hemisphere lesions led to ipsilateral decrements in reaction time, and lesions of either hemisphere diminished grip or pinch strength, finger tapping, and pegboard performance ipsilaterally. These results demonstrate that unilateral brain damage involving the motor areas of either hemisphere has detrimental effects on ipsilateral upper extremity motor function. Findings are discussed and related to the concept that the left hemisphere is specialized or has greater neuronal representation for bilateral motor processes. Physical therapists involved in the treatment of patients with hemiplegia should be aware that motor functions of the ipsilateral, nonparetic upper extremity may also be affected adversely by unilateral brain lesions. PMID- 2919191 TI - Health beliefs and health behaviors of physical therapists. AB - The purpose of this study was to examine the health beliefs and health behaviors of physical therapists. A survey questionnaire was sent to a 10% random sample of the physical therapists on the Texas licensure list for 1984, and 234 responses (69%) were used in the data analysis. The respondents tended to have positive health beliefs and good health behaviors in terms of a healthy life style. These findings have implications for physical therapists as role models for encouraging good health habits in their patients. PMID- 2919192 TI - Evaluation of eccentric exercise in treatment of patellar tendinitis. AB - The purpose of this study was to analyze the effects of a quadriceps femoris muscle eccentric training program on strength gain in patients with patellar tendinitis. The effect of an eight-week eccentric exercise program on quadriceps femoris muscle work was evaluated in four groups of subjects--two groups of "normal" (healthy) subjects and two groups of patients with patellar tendinitis. All four groups participated in a home muscle stretching exercise program, but only two groups--one group of normal subjects (N-A) and one group of subjects with tendinitis (T-A)--received additional eccentric training on an eccentric isokinetic dynamometer. The eccentric quadriceps femoris muscle work ratio (involved limb/uninvolved limb x 100) was used to quantify strength in the N-A and T-A Groups. Pain ratings were recorded for subjects with tendinitis before and after the eight-week experiment and were correlated with the dependent variable using a Spearman rank-order correlation coefficient. The N-A Group performed significantly better than all subjects with tendinitis (p less than .05). Subjects in the T-A Group, however, showed a trend toward increasing eccentric quadriceps femoris muscle work capacity over the eight-week training period. As pain ratings in the T-A Group increased, work ratios decreased. We concluded that eccentric exercise may be an effective treatment for patellar tendinitis, but that knee pain may limit optimal gains in strength. PMID- 2919193 TI - Age and passive ankle stiffness in healthy women. AB - The purpose of the study was to evaluate passive joint stiffness in ankles of young (aged 21-40 years; n = 15), middle-aged (aged 41-60 years; n = 15), and young elderly (aged 61-80 years; n = 15) women. The effect of knee position on passive joint stiffness was also evaluated by testing the subjects with the knee flexed (90 degrees) and with the knee extended (0 degrees). A torque motor system was used to record angular displacement and resistive torque during a 6 degrees/sec ankle rotation from 10 degrees of plantar flexion to 10 degrees of dorsiflexion (DF). Passive torque and passive elastic stiffness were measured at 0, 5, and 10 degrees of DF. Both measures increased nonlinearly as the ankle was rotated into DF, but showed no significant differences between the three age groups tested. There was also no significant difference in the passive stiffness measurements when the knee was flexed or extended. We concluded that within the range of motion tested, the factors of age and knee position do not affect the passive stiffness observed in the ankle joints of healthy women. We have now established baseline values of passive ankle joint stiffness for healthy women during DF within a functional ROM, which will be useful in the clinical evaluation of passive ankle joint stiffness and in studies where treatment efficacy is being investigated. PMID- 2919194 TI - Confidence limits for your ICC. PMID- 2919195 TI - A physiologist in Africa: lending a hand in developing countries. PMID- 2919196 TI - Effect of anterior chamber paracentesis on decreased retinal circulation due to retrobulbar hematoma in dogs. AB - An experimental canine model for blindness following blepharoplasty was developed to demonstrate occlusion of retinal circulation resulting from simulated retrobulbar hematoma. Seven mongrel dogs were studied, monitoring retinal vascular patterns by funduscopic examination and intraocular pressure by pneumotonometry. Anterior chamber paracentesis was performed in five dogs 10 minutes after injecting blood retrobulbarly, with an immediate decrease in pressure and return of retinal blood flow. In two dogs without paracentesis, increased pressure and blindness persisted. Anterior chamber paracentesis has been shown to reduce intraocular pressure from hematoma of the retro-orbital area in dogs. Although controversial, anterior chamber paracentesis may represent a useful temporizing adjunct in the treatment of increased intraocular pressure and impaired vision from hematoma following blepharoplasty. PMID- 2919197 TI - Semiquantitative correction of posttraumatic enophthalmos with sliced cartilage grafts. AB - A simple surgical technique for correcting posttraumatic enophthalmos is described. The steps are as follows: (1) a plaster mold is obtained of the patient's face, (2) wax is added to the enophthalmic eye of the plaster mold until it becomes symmetrical, (3) the quantity of wax is measured, and (4) the same amount of sliced costal cartilage is implanted beneath the periosteum of the extended orbital wall behind the vertical axis of the globe. Using this technique, we have successfully treated six patients with traumatic orbital floor defects without complication. This approach is useful for decreasing the orbital volume using a semiquantitative procedure to estimate the amount of graft material required. In this respect, costal cartilage demonstrates a marked advantage, with stability and cosmetic appearance verified over 12 months of follow-up. PMID- 2919198 TI - Submandibular gland resection and bilateral parotid duct ligation as a management for chronic drooling in cerebral palsy. AB - The control of chronic drooling in cerebral palsy has been difficult in the past. Previous methods to control drooling include the Wilkie procedure, which diverts the salivary flow from the parotid glands by means of surgically created tunnels to the tonsillar fossa, along with submandibular gland resection. An alternative is submandibular gland resection with bilateral parotid duct ligation. Previous published studies using this method have resulted in good to excellent results, but population sizes were felt to be too small to be conclusive. Since 1979, a total of 58 patients have been treated by parotid duct ligation with submandibular gland resection, and 86 percent have shown good to excellent results. These results compare favorably with those published by Wilkie. Also, parotid duct ligation is technically easier, associated with less postoperative morbidity, and has shown a decreased duration of hospitalization compared to parotid duct transposition. PMID- 2919199 TI - Comparison of compression and torque measurements of self-tapping and pretapped screws. AB - The choice of an internal fixation system for maxillofacial surgery is made difficult because of lack of information with respect to functional load. This study attempted to clarify some of the controversy with respect to maxillofacial use of these implants. Maximal compressive force to torque values were measured in standardized bone thicknesses of 1, 2, 3, and 4 mm. The screws tested were pretapped AO 1.5-, 2.0-, 2.7-, and 3.5-mm rescue screws and self-tapping Luhr, Champy, and AO 1.5- and 2.0-mm screws. Ten measurements were made for each screw type/bone thickness combination using a piezoelectric washer and torque screwdriver. It was apparent that for 1- and 2-mm bone thicknesses the use of self-tapping screws resulted in the highest compression values. In 3- and 4-mm bone thicknesses, pretapped screws offered the highest compression values. As expected, self-tapping screws had the highest torque values on insertion owing to torque loss in cutting the screw threads. The 2.7-mm screw offered no advantage over the 2.0-mm screws in 1- and 2-mm bone thicknesses but resulted in higher compression values in 3- and 4-mm bone thicknesses. PMID- 2919200 TI - Intralesional corticosteroid therapy for infantile hemangiomas. AB - Intralesional corticosteroid injections were performed in 31 hemangiomas in 30 infants aged 1 to 10 months at first injection. One to five injections were given, spaced 6 weeks apart. Lesions were located throughout the head and neck region, except one that was on the buttock. A mixture of betamethasone acetate and triamcinolone acetonide was used. Four lesions (13 percent) virtually disappeared, ten (32 percent) showed greater than 50 percent reduction in volume, ten (32 percent) showed definite but less than 50 percent reduction in volume, and seven (23 percent) showed little or no decrease in size. None showed further growth. All injections were performed without anesthesia, and there were not significant complications. We conclude that intralesional corticosteroid injections are safe and effective in properly selected infants with hemangiomas. PMID- 2919201 TI - Superomedial pedicle technique of reduction mammaplasty. AB - A series of 148 patients who underwent reduction mammaplasty utilizing the superomedial pedicle technique is presented. Resections as large as 4100 gm per breast with nipple-areola transpositions up to 30 cm were done with reliable nipple-areola survival, including preservation of sensation. The superior pedicle technique of breast reduction is recognized by many as technically easier and capable of producing a longer-lasting aesthetic effect. Classically, however, it has been limited to smaller resections. By incorporating the medial quadrant in the superior pedicle, more aggressive reductions can be safely undertaken with the same excellent results. Details of the procedure, the anatomic basis for its success, and complications are discussed. PMID- 2919202 TI - Calf implantation. AB - The process of calf implantation has been standardized by the author, who uses routine incisions and develops a subfascial pocket before inserting the oblong implants of different sizes. The evolution of the technique has led to a series of satisfactory results and a small percentage of complications. One-hundred and twenty-one patients with implantation had satisfactory increases in calf circumference. Complications included infections and capsule formation, which were dealt with in a satisfactory manner. PMID- 2919203 TI - Scanning electron microscopy and gel electrophoresis of vascularized periosteal autografts. AB - This study was devised to investigate the morphologic and biochemical sequence of events occurring during early periosteal osteogenesis in vascularized periosteal flaps. A pleuroperiosteal flap based on the intercostal vessels was developed and rotated onto the chest wall in 12 adult dogs. Animals were sacrificed at intervals between 7 and 60 days, and the flaps were removed with the underlying muscular bed. Specimens were studied by tetracycline uptake, gel electrophoresis, light microscopy, and the scanning electron microscope. Osteoprogenitor cells were seen as early as 7 days after transfer. Collagen fiber deposition was vigorous and noted in all specimens with rapid mineralization by 9 to 15 days. There was no structural or vascular interaction between the flaps and the recipient muscular bed. Gel electrophoresis confirmed the presence of type I and III collagen, with an increase in type I collagen over time. The pattern of collagen deposition and the final bony architecture resembled that of woven bone. PMID- 2919204 TI - The rating game. PMID- 2919205 TI - The Tessier number 9 cleft. AB - The clinical, radiologic, and operative examination of two patients with the Tessier number 9 cleft has allowed the first complete description of this, the rarest of the rare craniofacial clefts. Soft-tissue disruption extends from the lateral third of the upper eyelid through a distorted lateral end of the eyebrow to the temporal scalp, with an associated hairline indicator. The skeletal disturbance similarly radiates superolaterally from the superolateral orbital rim across the greater wing of the splenoid to the upper squamous temporal. The three dimensional extent of the bony disruption is associated with distortion of the cranial base and calvaria above. PMID- 2919206 TI - Composite in situ vein bypass for upper extremity revascularization. AB - Chronic upper extremity arterial insufficiency is rare. Consequently, major reports specifically limited to the topic are scarce, and the clinical experience is small. In addition, symptomatology, diagnostic criteria, and guidelines for surgical management remain ill-defined. In the lower extremities, however, in situ vein bypass has been attempted for nearly three decades. This technique offers many advantages over traditional revascularization methods. Although the procedure has become popular for the lower extremity, no report of its use in the upper extremity is found in the literature. We report what may be the first case in which in situ bypass was used in the upper extremity for a threatened limb secondary to diabetic occlusive vascular disease complicated by a previous shunt used for hemodialysis. Revascularization of the upper extremity using the in situ vein bypass technique may offer a new alternative to traditional methods of revascularization. PMID- 2919207 TI - A simple technique for locating the umbilicus in abdominoplasty. AB - A method for locating the umbilicus in abdominoplasty is described. The method utilizes a magnet sutured to the umbilical stalk and a locking device which determines the exact location of the umbilicus. PMID- 2919208 TI - The use of adhesive tape to inform the patient preoperatively. PMID- 2919209 TI - The management of hypertrophied inferior turbinates. PMID- 2919210 TI - Reconstruction of the preputium in distal hypospadias. PMID- 2919211 TI - Ganglions of the temporomandibular joint. PMID- 2919212 TI - Use of transillumination in tissue expansion. PMID- 2919213 TI - Happy ending to suffering. PMID- 2919214 TI - AAAAA--crawling to the top and why I rode with Wojcik. PMID- 2919215 TI - Legal, ethical, and moral issues in plastic surgery. PMID- 2919216 TI - Mammography as a cause of firmness after augmentation mammaplasty. PMID- 2919217 TI - Use of the laser in treatment of carpal tunnel syndrome. PMID- 2919218 TI - Uvulopalatopharyngoplasty. PMID- 2919219 TI - Repair of ruptured orbicularis oris in trumpet players. PMID- 2919220 TI - Galactorrhea after reduction mammaplasty. PMID- 2919221 TI - Use of the expander to estimate the volume required in reconstructing the breast. PMID- 2919222 TI - Lectinhistochemical study of cell surface alterations in mouse embryos exposed to low radiation doses. AB - The peroxidase-coupled Dolichos biflorus agglutinin (DBA) served as a marker for cell surface alterations in embryonic mouse tissues exposed to low-dose radiation during the early organogenesis (day 9 post conception). In unirradiated embryos, DBA bound selectively to various organ primordia, depending on their differentiation state. The auditory vesicles and the developing blood vessels were the only tissues staining strongly with the lectin. The vascular endothelia also showed the highest radiosensitivity, expressed by the maximal reaction already at 12.5 cGy. Marked surface changes as well were registered in the basal part of the Rathke's pocket and in the roof of the diencephalon. After exposure to 25 cGy, a transient amplification of the reaction as compared with 12.5 cGy occurred firstly in the Rathke's pocket, then in the infundibulum and in auditory vesicles. The most distinct effects were achieved with 50 cGy. Remarkable is the prompt rise of the DBA-affinity in a narrow area of the myelencephalon, and subsequently also in the roof of the diencephalon. Furthermore, the infundibulum and the Rathke's pocket, both anlagen of the pituitary gland, bound heavily DBA during the entire examination period of 24 h. The present study demonstrated the outstanding suitability of the Dolichos biflorus agglutinin for histochemical detection of subtle cellular alterations by small radiation doses. PMID- 2919223 TI - X-ray dose-effect relationship on unscheduled DNA synthesis and spontaneous unscheduled DNA synthesis in mouse brain cells studied in vivo. AB - X-irradiation of the head of adult mice leads to DNA repair synthesis (unscheduled DNA synthesis, UDS) in non-proliferating cells of the brain as shown autoradiographically after injection of 3H-thymidine and subsequent irradiation. The extent of UDS induced by one and the same X-ray dose varies between different cell types and also between different brain areas. Within the range of X-ray doses studied (2 to 100 Gy) a linear dose effect relationship was observed. No evidence of a saturation effect was found. The slopes of the regression lines for the dose effect relationship differ considerably for the different cell types. Two interesting correlations were found, if the present results were compared with other data in the literature: (i) There seems to be a correlation between the extent of UDS and radiosensitivity of the different cell types, the cells with low DNA repair synthetic rates being more radiosensitive. (ii) The extent of UDS of the different cell types correlates well with the extent of protein synthesis of the corresponding cell types. Apart from radiation induced UDS, spontaneous UDS was found to occur in sham-irradiated animals. The extent of spontaneous UDS also differs considerably between different cell types as well as between different brain areas. The increase of spontaneous UDS with increasing duration of immobilization of the animals during sham irradiation suggests a relationship between spontaneous UDS and stress. PMID- 2919224 TI - Radiation-induced changes of structural and functional properties of human hemoglobin. I. Spectral characterization of irradiated deoxyhemoglobin. AB - Structural changes of human deoxyhemoglobin (deoxyHb) induced by water and ethanol radicals were investigated in this study using absorption spectroscopy. Spectra of deoxyHb samples irradiated under various conditions (the atmosphere of argon or N2O in the absence or presence of ethanol) indicate their conversion into methemoglobin (metHb), hemichrome- and cholehemichrome-like products. The absorbance at the characteristic maxima of these derivatives and also of the oxidized or reduced samples following irradiation depends on the dose of radiation and the conditions employed. PMID- 2919225 TI - Radiation-induced changes of structural and functional properties of human hemoglobin. II. Structural and functional characterization of irradiated deoxyhemoglobin. AB - Gel filtration and SDS-PAGE separation of hemoglobin (Hb) irradiated under argon or N2O show formation of covalent-aggregated Hb molecules. The production of covalent bonds is attributed mainly to the action of hydroxyl radicals, because addition of ethanol, a scavenger of these radicals, suppresses this reaction to a great extent. The oxidized heme iron forming metHb or hemichromes is found in all the separated fractions of irradiated Hb. It is also found that the radiation modified Hb molecules exhibit a decrease of co-operative binding of oxygen. PMID- 2919226 TI - UV-A induced lipid peroxidation in liposomal membrane. AB - UV-A (365 nm) produced a dose-dependent linear increase of lipid peroxidation, as detected by the assay of malondialdehyde (MDA). MDA formation was inversely related to the UV-A dose rate. Sodium formate and ethylenediaminetetra acetic acid (EDTA) could not inhibit by any significant degree the UV-A induced MDA formation. While butylated hydroxy toluene (BHT) caused about 85% inhibition, sodium azide and L-histidine produced 45-50% inhibition of MDA formation. The involvement of singlet oxygen (1O2) in the UV-A induced lipid peroxidation is discussed. PMID- 2919228 TI - Magnetic resonance imaging: a brief review of image contrast. AB - Because MRI is sensitive to tissue properties that are quite different from those exploited by traditional x-ray technologies, it has provided a highly sensitive new way of looking at the human body. This article summarizes the basic mechanisms of contrast in proton MR images, examining the phenomena responsible and the user's ability to manipulate contrast through system parameters. The intended purpose is to impart a qualitative, intuitive understanding of these mechanisms to the newer user. PMID- 2919227 TI - Thermoregulatory responses of rats exposed to 9.3-GHz radiofrequency radiation. AB - Ketamine-anesthetized Sprague-Dawley rats were exposed in H orientation to far field 9.3-GHz continuous-wave (CW) and pulsed (2 microseconds, 500 pps) radiofrequency radiation (RFR) at average power densities of 30 and 60 mW/cm2 (whole-body average specific absorption rates of 9.3 and 18.6 W/kg, respectively). Irradiation was conducted to cyclicly increase colonic temperature from 38.5 to 39.5 degrees C. Colonic, tympanic, and subcutaneous temperatures, ECG, blood pressure, and respiratory rate were continuously recorded during experimentation. At both power densities, the subcutaneous and tympanic temperature increases significantly exceeded the colonic temperature increase. At both exposure levels, heart rate increased significantly during irradiation and returned to baseline when exposure was discontinued. Blood pressure and respiratory rate did not significantly change during irradiation. There were no significant differences between the effects of CW and pulsed RFR exposure. The levels of subcutaneous heating and heart rate change were greater, and the times required to achieve and to recover from a 1 degree C colonic temperature increase were longer than in previous studies conducted at 2.8 GHz. Results of these studies indicate that the carrier frequency used during irradiation markedly affects the pattern of heat distribution and the physiological responses of RF irradiated animals. PMID- 2919229 TI - MRI of the head and neck. PMID- 2919230 TI - The role of gadolinium-DTPA in the evaluation of extracranial head and neck mass lesions. AB - Based on our experience with 28 patients, there is good evidence that gadolinium enhanced MR will be useful in evaluation of skull base involvement, sinus involvement, or intracranial extension by neoplasms that involve the neck above the hard palate. This region has historically been a difficult area to image with any modality, because of the detailed anatomy and numerous important structures that traverse it. Gadolinium-enhanced MR should provide a valuable tool in the evaluation and management of these patients. The evidence that gadolinium is useful in staging of primary and nodal squamous cell carcinoma of the extracranial head and neck is less apparent. Areas where gadolinium may be helpful include size and extent of primary tumor and internal architecture of nodes that do not meet size criteria for malignant adenopathy. This is an area in which more experience is necessary, employing careful correlation with enhanced CT, unenhanced MR, and surgical specimens. Posttreatment follow-up of head and neck squamous cell lesions is a potential use for gadolinium, but this too is yet to be adequately studied. We have found that gadolinium enhancement provides no additional information important to the management of benign head and neck lesions over enhanced CT or unenhanced MR. PMID- 2919231 TI - MR-directed needle biopsies. AB - New generation stainless steel alloys have enabled the development of needles which can be used for MR-guided biopsies. Biopsy under MR guidance has the advantages of greater tissue contrast resolution, lack of ionizing radiation, and variable angle oblique imaging planes. The biopsy approaches and imaging techniques are described. PMID- 2919232 TI - [X-ray diagnosis of renal osteopathy in dialysis patients with reference to clinical aspects]. AB - Pathophysiological histological and radiological findings in renal osteodystrophy are described. Special emphasis is laid on secondary hyperparathyroidism. Preliminary results of the authors' investigations show a good correlation between radiological findings in the phalanges of the hand and the concentration of parathyroid hormone (PTH) in 14 patients. The concentration of the hormone in the blood was measured by a new "two-site" immunoradiometric assay, which is specific for the intact, biologically active hormone. Patients with high concentrations of PTH in the blood tended to have more severe radiological changes. In 4 patients for whom radiographs of the hands revealed no pathologic findings, normal PTH concentrations in the blood were measured by this method, whereas the conventional assay gave elevated hormone concentrations for the same patients. This is due to the lack of specificity of the conventional method for the intact, biologically active hormone. Nevertheless, further investigations are needed to confirm these findings. PMID- 2919233 TI - [Radiotherapy with increased efficacy]. AB - The introduction of iodine atoms into a malignant tumor by intravenous injection of a contrast medium that is excreted by way of the kidneys selectively increases the tumor's capacity for the absorption of X-ray photons. This effect is exploited in CCT, but in high-voltage X-ray therapy it leads to an elevated focal dose while the incident dose remains the same. PMID- 2919234 TI - [A strange calcification on/in the thorax. A dorsal pleural calcification following long-term drainage of a splinter injury and pleural empyema on the right]. PMID- 2919235 TI - [The axillary brachial plexus block. A study of 178 patients]. AB - Success rates and complications were studied in 178 patients scheduled for brachial block. METHODS. Patients of both sexes aged 9 to 79 years received axillary blocks in order to permit typical surgical procedures of the hand an forearm. The block was performed using the transarterial method described be Dejong. Half of the local anesthetic was administered anterior to and half posterior to the axillary artery. The incidence of successful blocks, latency time, and systemic complications were investigated; 14 days after the blocks, motor function and sensation were examined in order to evaluate the local neurological status. RESULTS. The rate of successful blocks averaged 79% using 40 ml 1% mepivacaine after 12 min latency; this rate was increased to 89% by administering a further 20 ml 1% mepivacaine. Disagreeable sensations from the operative field occurred in 5% and mild symptoms of cerebral toxicity in 2.8% of cases; 1.6% of patients had cardiovascular disturbances such as hypotension or arrhythmias. Local complications such as hematomas were found in 17.5% local pain in the axillary region in 15%, and long-lasting paresthesias in 12% of cases. DISCUSSION AND CONCLUSIONS. The 90% rate of successful blocks is comparable to the range of 86-98% presented in the literature. The success rate depends on the definition of successful block, the experience of the anesthetist, and the volume and concentration of the anesthetic solution administered. The incidence of systemic cardiovascular complications was similar to that in the literature, but we observed fewer symptoms of cerebral toxicity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2919236 TI - [Thoracic peridural anesthesia in childhood]. AB - Local and regional anesthesia, especially peridural anesthesia, is a rarely used method in pediatric anesthesia. That cannot be explained by children's physis, since it shows in general neither a different margin of therapeutic safety nor a different effect/side-effect ratio than in adult. Nevertheless, psychologic alteration of children through operation and anesthesia necessitate simultaneous endotracheal narcosis during peridural anesthesia. The following characteristics of regional anesthesia in children should be regarded: The younger the child the higher is the ratio between extracellular water and body weight. Thus higher doses of local anesthetics in relation to body weight can be applied. The smaller diameters of children's nerves support diffusion of local anesthetics and, therefore, allow the use of lower concentrations. Increased perfusion of tissues and high cardiac output lead to rapid resorption and accelerated increase of anesthetic blood levels. This disadvantage can be avoided by use of lower concentrations of anesthetics. Even an extended sympathetic block during peridural anesthesia hardly causes any negative effect on circulatory parameters. We performed thoracic epidural anesthesia during thoracic and upper abdominal surgery in 40 5-15-year-old children. In many of the patients additional risks had already occurred through atelectasis or lung fibrosis. Before introducing the epidural catheter we always carried out endotracheal anesthesia with relaxation to achieve perfect conditions for the puncture. This puncture was made between Th 6 and 10, mostly between Th 7/8, the patient lying on one side. An extension of analgesia between Th 3 and Th 12 was intended, which, however, could not be controlled because of simultaneous endotracheal anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2919237 TI - Flow cytometry: diagnostic applications. PMID- 2919238 TI - Organization and operation of a flow cytometric immunophenotyping laboratory. AB - Technical advances in the field of flow cytometry have made it feasible for many academic and private hospital laboratories to purchase relatively inexpensive "user friendly" flow cytometers that do not require dedicated flow cytometer operators, special rooms, or a significant amount of laboratory space. Because the financial and physical constraints in operating a flow cytometer have been substantially reduced, many pathologists may now be considering such a purchase. By chronicling the clinical activities of a single flow cytometric immunophenotyping laboratory, this report will answer a variety of questions that may be asked by pathologists regarding both the utility of flow cytometers in clinical diagnosis and the mechanics of operating an immunophenotyping laboratory. The types of tissues that can be evaluated by flow cytometry will be detailed, and we will summarize the number and type of flow cytometric clinical studies performed in our laboratory since its development in 1983. Practical aspects of laboratory operation including technical staff requirements, specimen handling and processing procedures, monoclonal antibody selection, and quality control procedures will be presented. In addition, a comprehensive review of flow cytometric immunophenotyping studies as applied to the diagnosis of leukemias, lymphomas, and immunodeficiency disorders will be presented along with case examples that illustrate our approach to the interpretation of immunophenotyping results. PMID- 2919239 TI - Effects of corpus callosum stimulation on the morphology and frequency of epileptic bursts in the feline topical penicillin generalized model. AB - Twelve cats were stimulated at the rostrum of the corpus callosum while full epileptic activity was recorded after topical application of penicillin on the cortex bilaterally. Electrocorticography was performed bilaterally. In 6 animals the electrode position was checked by evoked potentials. Stimulation parameters ranged from 0.5 to 1,000 Hz, from 2 to 10 mA, and from 0.5 to 5.0 ms. No significant modification was found in frequency, synchrony, and morphology of the epileptic bursts and spikes, suggesting that callosal stimulation, at least using this model, is ineffective in reducing epileptic activity. PMID- 2919240 TI - Statistical and mathematical modeling of the AIDS epidemic. Papers from a conference. Baltimore, Maryland, 17-18 November, 1987. PMID- 2919241 TI - A model of the spread of HIV infection and the demographic impact of AIDS. AB - The objective of the computer simulation model described here is to project, for periods up to one or more decades, the annual incidence and prevalence of HIV infection and AIDS in a population with given epidemiological, behavioural and demorgraphic characteristics. In addition, the epidemic's impact on a range of demographic variables is calculated. The epidemiological components of the model use a compartmental approach and they are described with sets of linear differential equations. The demographic framework in which the epidemiological components are integrated, is based on a standard cohort component method of population projection. The simulated population is stratified by age, gender, sexual behaviour, marital status and infection/disease status. The concluding section provides an illustrative application of the model to a Central African population. In this hypothetical simulation covering the period from 1975 to 2000, HIV prevalence in the adult population rises from 0 to 21 per cent. By the end of the projection period mortality is about double the level that would have prevailed in the absence of the epidemic, but, owing to the very high birth rates that prevail in most of Africa, the growth rate of the population remains substantially positive. PMID- 2919242 TI - Some stochastic models of AIDS spread. AB - In this paper we propose a stochastic model for the AIDS spread in a homosexual population. The probability generating function (PGF) of the numbers of latent persons, infective persons and AIDS cases is derived. By using the PGF, it is shown that the expected numbers and variances and covariances of these persons satisfy some ordinary differential equations. These equations have been solved numerically to assess effects of various factors on AIDS spread. PMID- 2919243 TI - Policy implications of modelling of the AIDS epidemic. AB - Health policy issues associated with AIDS are complex and controversial, including health care, research priorities, education, testing and confidentiality. Modelling may provide information relevant to their solution. Estimates of the future numbers of symptomatic persons and of the mix of severity are necessary for developing the capability to provide and fund health care services. Models may suggest other data needs and research directions. An important policy role of models is to permit evaluation of potential intervention steps and especially to project negative consequences. The critical contribution of models will be improved understanding of the dynamics of the AIDS epidemic. PMID- 2919244 TI - Statistical methods for short-term projections of AIDS incidence. AB - Short-term projections of AIDS incidence are critical for assessing future health care needs. This paper focuses on the method of back-calculation for obtaining short-term projections. The approach consists of back-calculating from AIDS incidence data through use of the incubation period distribution to obtain estimates of the numbers previously infected. The numbers previously infected are then projected forward to obtain short-term projections. An approach is suggested for accounting for new infections in short-term projections of AIDS incidence. Back-calculation requires accurate AIDS incidence data. A method which is computationally easy to implement is proposed for estimating the distribution of the delays in reporting AIDS cases. It was found that the reporting delay distribution in the United States varies by geographic region of diagnosis. Back calculation also requires a reliable estimate of the incubation period distribution. Statistical issues associated with estimating the incubation period distribution are considered. The methods are applied to obtain short-term projections of AIDS incidence in the United States. The projected cumulative AIDS incidence in the U.S. by the end of 1992 was 287,100 under the assumption that there are no new infections after 1 July 1987, and 330,600 under the assumption that the infection rate remains constant. These projections do not account for the new broadened AIDS surveillance definitions or the underreporting of AIDS cases to the Centers for Disease Control. PMID- 2919245 TI - Statistical methods for monitoring the AIDS epidemic. AB - This article describes statistical methods for monitoring the epidemic of the acquired immunodeficiency syndrome (AIDS). A log-linear model is proposed to estimate AIDS incidence and its growth rate while taking account of delays in case reporting. An empirical Bayes approach for estimating the epidemic growth rate in low prevalence subgroups is introduced. These methods are illustrated with an analysis of AIDS incidence trends for seven risk groups in each of six geographic regions using the Centers for Disease Control AIDS case registry data as of September 1987. The analysis finds that AIDS incidence is currently doubling about once every two years and that the relative composition of new cases is shifting away from the older epidemics such as in north-eastern homosexual communities. PMID- 2919246 TI - The value of AIDS incidence data in assessing the spread of HIV infection. AB - Changes over time in the cumulative number of cases of AIDS depend in a complex way on several features of the epidemic, including the distribution of the induction time between infection with the human immunodeficiency virus (HIV) and onset of symptoms of AIDS, heterogeneity in such behaviours as sexual practices, selection of partners, and IV drug use, and changes over time in these behaviours. Consequently, the observed increase in the doubling time in cumulative AIDS incidence from 5 to 13 months, since AIDS was first recognized in 1982, demonstrates neither that the epidemic has begun to 'run its course' nor that behavioural changes have had a major impact in reducing incidence. Even in a homogeneous population with known induction distribution, AIDS incidence data currently are of little value in determining the number of persons infected with HIV unless additional information is available about the shape of cumulative incidence curve of HIV infection. PMID- 2919247 TI - Models for the HIV infection and AIDS epidemic in the United States. AB - Statistical models of the HIV infection epidemic in the U.S. which account for the observed incidence of AIDS cases in the years 1978-1987 are considered. The models assume a known distribution of times from infection to AIDS. The best model estimates that there were approximately 563,000 to 1,110,000 individuals infected in the U.S. in April 1987. These estimates do not take into account underreporting of AIDS cases. The sensitivity of the conclusions to the model's assumptions is ascertained by investigating a variety of parametric models for the infection epidemic, a variety of likely distributions for the time from infection to AIDS, and some plausible alternatives for the history of AIDS cases in the U.S.. It is concluded that there is too much uncertainty in the data and the models to be able to give highly accurate predictions of the number of people currently infected in the U.S., however, the results from the best fitting models suggest that there are less than the 1 to 1.5 million infected as estimated by the Centers for Disease Control. A Bayesian scheme is suggested for incorporating the uncertainty in the models. PMID- 2919248 TI - Disease prevention models of voluntary confidential screening for human immunodeficiency virus (HIV). AB - Epidemic models are developed to evaluate the potential benefits of voluntary confidential testing (VCT) for HIV. The number of tests required to prevent one case (called the economic ratio ER), and the number of cases prevented by the screening programme are calculated. Methods differ from commonly used epidemic models because susceptibles and infecteds are subdivided according to testing status, to permit modelling of the efficacy of knowledge of HIV status in retarding epidemic spread. The methods also allow for subdivision into several homogeneous subpopulations whose members may be attracted in varying degrees to members of other subpopulations. Thus the common assumption of free mixing across subpopulations is relaxed. The following conclusions which refer to a population of 100,000 persons over a period of 5 to 15 years, are robust to wide variations in assumed parameter values and other aspects of modelling: 1. VCT prevents hundreds or thousands of infections in isolated high risk populations and ER values are typically less than 100 making VCT very attractive economically. 2. VCT prevents only a few infections in isolated low risk populations with initial prevalence 0.1 per cent or less, and the ER values are well above 2000. However, in 'low risk' populations with 1 per cent initial prevalence, tens or hundreds of infections may be prevented, and ER values fall below 2000 for plausible spread rates, indicating that VCT may be economically feasible in such settings. 3. In a mixed population of gays, bisexuals and heterosexuals, a VCT programme that aims primarily at the gay/bisexual subpopulations prevents more disease in the gay/bisexual populations, prevents more disease in the heterosexual populations, and requires fewer tests per case prevented than a VCT programme that tests all subpopulations equally. PMID- 2919249 TI - The number of partners and the probability of HIV infection. AB - This paper analyses the probability of contracting the AIDS virus in relation to the number of sexual contacts and the number of different partners. It is shown that in the case of a fixed number n of sexual contacts there is the following ranking from least risk to greatest risk: 1. a monogamous relationship with a non infected partner; 2. a monogamous relationship with a randomly selected partner; 3. a relationship with more than one randomly selected partners; 4. n randomly selected partners; 5. a monogamous relationship with an infected partner. PMID- 2919250 TI - Heterogeneity in the probability of HIV transmission per sexual contact: the case of male-to-female transmission in penile-vaginal intercourse. AB - Recent studies have indicated variation in the infectivity beta of HIV among heterosexual couples. We represent this heterogeneity by modelling beta as a random variable. Using data on the number of contacts and seroconversion of couples, we fit the model by maximum-likelihood estimation with a beta distribution and a discrete distribution for beta. The estimates indicate the heterogeneity is extreme. The limitations of the model and the implications of the results for epidemiologic spread and further research are discussed. PMID- 2919251 TI - [AIDS and other sexually transmitted diseases. A videocasette from the University Dermatology Department in Zurich]. PMID- 2919252 TI - [Plasma cell leukemia]. AB - The following article describes five patients with plasma cell leukemia treated during the last two years at a Medical University Polyclinic. Plasma cell leukemia is a disease which was seen extremely rarely in the past. The disease can develop in patients with multiple myeloma or, even more rarely, as a "de novo" disease. Generally patients with plasma cell leukemia are younger than the multiple myeloma patients and have a higher incidence of organomegaly. Despite the fact that patients with plasma cell leukemia received the same intensive chemotherapy as those with multiple myeloma, their prognosis was considerably worse, with a median survival time of only five month. PMID- 2919253 TI - [The assessment of anxiety in somatic patients--a pilot study]. AB - 16 patients of the Medical ambulatory at the University of Basel born between 1940 and 1945 were explored with the State-Trait Anxiety Inventory (STAI) of Spielberger for the presence of anxiety. With this self-rating inventory state anxiety as well as general trait anxiety can be recognized. The examined group was not selected on specific diagnoses. Two patients with a heavy organic disease (Aids, Friedreich's ataxia) showed an increased state anxiety and an increased general trait anxiety. Six patients with hypertension showed decreased, average as well as increased values of state anxiety and general trait anxiety. In one patient with epilepsia decreased general trait anxiety and average state anxiety were manifest. A patient with a depressive neurosis and functional abdominal pain showed increased general trait anxiety and average state anxiety. Finally, in six patients with different diseases, such as patients with different diseases, such as bronchitis, diabetes, coronary and congestive heart disease, obesity and myalgias, no deviation of their state and general trait anxiety values was evident when compared with standard values. The results are discussed. PMID- 2919254 TI - [Hypertension]. AB - This 40 year old man had been treated adequately for arterial hypertension over the last 10 years. Within one year this arterial tension rose continuously in spite of treatment. A low blood-potassium value found on routine chemical analysis prompted an investigation on secondary causes for hypertension. The results of a peripheral renin-study were typical for secondary aldosteronism. An abdominal aortography and selective angiography of the renal arteries visualized an intrarenal arterial aneurysm with stenoses as causative factor of the renovascular hypertension. Antihypertensive treatment with an ACE-blocker permitted to normalize the blood-pressure values subsequently. PMID- 2919255 TI - [A case from practice (127). Patient: Mrs. M. S., born 1952, housewife]. PMID- 2919256 TI - [Intestinal drug smuggling--a new diagnostic and therapeutic problem]. AB - Since spring 1985 81 persons were examined because of suspected intestinal drug smuggling (body-packing). 46 patients (57%) had drug-packages in the gastro intestinal tract, in 35 persons (43%) the suspicion was not confirmed. 26 patients had swallowed the drugs (mostly cocaine) whereas in 20 cases drugs were found in the rectum (mostly heroine). Most important for diagnosis was abdominal x-ray whereas in our hands abdominal sonography was unreliable. When body-packing is diagnosed, observation and mild laxative in conjunction with sufficient beverages are recommended. Serious complications in our series comprised one patient with mechanical ileus and another with heroine-poisoning after rupture of a package. PMID- 2919257 TI - [Exertional dyspnea, fatigue, palpitations]. AB - This 52-year old female patient suffered from exertional dyspnea, fatigue and palpitations progressive for some months. She had rheumatic fever in childhood. Physical examination and echocardiography revealed severe pure mitral regurgitation, invasive studies showed dilatation of the left atrium and ventricle, a regurgitant volume of 70% of the stroke volume and mitral valve replacement was performed. PMID- 2919258 TI - [A case from practice (128). Patient: Mr. B. L., born 1947, engineer]. PMID- 2919259 TI - [Computed tomography and conventional x-ray diagnosis of tumor bone lesions]. AB - The informative value of conventional x-ray film and computed tomography was analysed on the basis of findings in 214 patients having 9 primary and 189 secondary malignant tumours as well as 16 benign bone tumours. In 44% of the benign bone tumours CT yielded decisive additional information in so far as it became possible to determine the type of tumour (4) or the paraosseous tumour extension (3), respectively. The tumour status of the primary malignant tumours was determined throughout via x-ray film, whereas intraosseous and extraosseous extension of the tumorous process was covered much better by computed tomography. CT did not yield additional information in 28% of the secondary malignant bone tumours, whereas 33% of the osseous destructions--depending on the size and localisation--could be identified only via computed tomography. Decisive additional information was gained via CT in 39% of the patients mainly in respect of intraspinal or endocranial tumour extension. PMID- 2919260 TI - [Radiotherapy of malignant lymphomas]. AB - Radiotherapy of malignant lymphomas has yielded excellent results especially in Hodgkin's lymphomas. A high rate of freedom from recurrences combined with a low rate of side effects can be achieved only with optimal radiotherapy. Benefit/risk analyses shows that the side effects are in a favourable proportion to the results achieved. PMID- 2919261 TI - [Diagnosis and therapy of differentiated thyroid cancer]. AB - Summing up, we can state the following: Diagnosis of thyroid cancer seems easy, since the organ lies immediately beneath the skin, so that tumour growth could be readily detected, and also since thyroglobulin (tg) is an ideal and well-tried tumour marker. Nevertheless, malignant thyroid nodes are still frequently misinterpreted as benign, as benign strumae occur quite often. In view of the fact that malignant follicular carcinomas have a tendency to produce metastases via the bloodstream, in all tumours larger than 1 cm to 1.5 cm no change should be made in the classical therapeutic approach (total thyroidectomy, radioiodine therapy and levothyroxine suppression therapy), whereas in so-called occult papillary thyroid cancer (i.e. carcinomas smaller than 1-1.5 cm) hemithyroidectomy and lifelong suppression therapy can be satisfactory. It follows from this that in view of the low complication rate even with maximal therapy of differentiated thyroid cancer and the advantages resulting therefrom for follow-up care, the total ablation therapy should be retained as standard treatment. The low incidence of thyroid cancer justifies, inter alia, central follow-up care, the more so since this is usually performed on an interdisciplinary basis and there is as yet no standardised procedure for thyroglobulin determination. PMID- 2919262 TI - [MRT of intrathoracic space-occupying lesions--conventional and new rapid study technics]. AB - 100 patients with histologically and cytologically confirmed intrathoracic space occupying growths were examined by CT and MR over and above conventional x-ray film diagnosis. MR tomography was performed in all the 100 patients via ECG triggered T1 and T2 weighted spin echo sequences. The last 35 patients were additionally examined via gradient echo sequences with which it is possible to examined 24 consecutive layers in any layer plane within 7 minutes without ECG triggering. Comparative evaluation of CT and MR tomography yielded an equally high degree of sensitivity when identifying intrathoracic growths. Compared to CT, determination of tumour status via MR tomography proved easier in individual cases. Other advantages of MR tomography were seen in the staging of bronchial carcinomas. Compared with conventional spin echo sequences the rapid gradient echo sequences reduced examination periods by more than 50%. In the cardiac region and the mediastinal structures that pulsate with it the diagnostic value of the gradient echo images is at present slightly impaired by fuzziness caused by movement. The image quality of the spin echo images is comparatively good in the regions of the superior and posterior mediastinum, the lungs and the thoracic wall. PMID- 2919263 TI - [Enuresis: the viewpoint of the urologist]. AB - After a description of the bladder-sphincter system physiology and of the different stages in the acquisition of micturition control by children, as revealed by urodynamic explorations, the author presents the bladder immaturity syndrome. This entity includes diurnal disorders of micturition--such as urgencies, pollakiuria, more seldom retention and incontinence--which can readily be identified by questioning. It accounts for many cases of nocturnal enuresis which may benefit from treatment with anticholinergic drugs. Nocturnal enuresis without disorders of micturition in daytime is due to other physiopathological mechanisms. It is preferably treated with tricyclic antidepressants and other non medicinal therapies. All cases should be investigated for a possible organic pathology. A practical classification of enuresis is given. PMID- 2919264 TI - [Respiratory disorders during sleep in children]. AB - Respiratory disorders that occur in children asleep are frequent. They are evaluated by studying the respiratory function at each stage of sleep, as determined by neurophysiological criteria, and they must be interpreted on the basis of what is known of respiratory adaptation during sleep in healthy infants. Respiratory disorders during sleep may be due to: (1) obstructive sleep apnoea syndrome caused by an obstruction of the upper airways, most frequently by enlarged tonsils; (2) nocturnal episodes of acute on chronic obstructive lung disease, such as cystic fibrosis, sequelae of viral infection, ciliary dysfunction, broncho-pulmonary dysplasia; (3) nocturnal asthma; (4) alveolar hypoventilation of central origin. The short-or long-term risk of respiratory disorders during sleep is their repercussions on pulmonary circulation and right heart function. PMID- 2919265 TI - [The child insomniac]. AB - The most frequent of sleep disorders in children are repeated and prolonged wakeful periods. One month old infants are normally awake during one-third of the nocturnal sleeping time. Gradually, sleep moves into night and wakefulness into daytime. At 3 years, 25 to 38% of children wake up during the night, but after 5 years this proportion becomes negligible. Apart from acute or chronic diseases which may produce sleep disorders, most of these are due to environmental factors. Two syndrome are worthy of special mention: deficiency of slow wave and deep sleep in psychosocial dwarfism, and insomnia due to intolerance to cow's milk. Treatment of insomniac children rests on behavioural techniques: parents must be helped to understand and observe the sleep-wake rhythm of their children and teach them to acquire regular sleeping habits. PMID- 2919266 TI - [Sudden death syndrome in the newborn infant and sleep]. AB - It seem increasingly obvious that sudden death is a multifactorial syndrome, the result of respiratory and/or cardiac dysfunction in responses to various causes. Cardiorespiratory and neurophysiological explorations performed during sleep have considerably increased our understanding of the syndrome. They have been at the root of all recent theories, and they make it possible to rule out a likely cause in infants "rescued" from sudden death. Some of these explorations may be used for screening purposes, as they sometimes evaluate the risk of apnea or cardiac accident capable of causing sudden death. The development of sleep during the first 6 months of life plays de determinant role in the syndrome. Slightly more than 80 p. 100 of deaths occur during a period of presumed sleep. The 1 to 6 months period is characterized by very rapid changes in the quality and organization of sleep: there is a substantial increase in quite sleep time, during which the child is most probably vulnerable, and a decrease in agitated sleep time which at that age is thought to protect against sudden death. This is also the period of life where sleep stability increases and where al circadian rhythms are constituted and harmonized with each other. The rapidity and nature of these changes probably makes this period a time of risk. Another factor of importance is the problem of sudden infant death is the ability to wake up. Recent studies have shown that infants believed to be at risk of sudden death seem to have disturbed awakening mechanisms. PMID- 2919267 TI - [Wake-sleep rhythm and school rhythm]. AB - Recent studies, and notably 24 hour polygraphic recordings, have provided accurate data on the qualitative and quantitative changes in the organization of sleep and wake periods which occur during childhood and adolescence. These studies explain the lack of adaptation of some subjects, notably young children and teenagers, to school hours. It is hoped that this knowledge of changes in circadian rhythms will be taken into account by those who decide on working hours in schools. PMID- 2919269 TI - [Epidemiology and prevention of cancer of the uterine cervix]. PMID- 2919268 TI - [Simplified treatment of poisoning by ethylene glycol]. PMID- 2919270 TI - [Ontogenesis and organization of sleep]. AB - The newborn infant spends three quarters of his time asleep, while at adulthood his sleep will occupy only 8 hours out of 24. The development of sleep and wakefulness is continuous from before to after birth, and follows a progressive pattern: first rapid in the perinatal period and until one year of age, then much slower until puberty. Schematically, the ontogenetic organization of the states of vigilance consists of: 1. the building up of a circadian sleep-wake rhythm and the lengthening of the ultradian Basic Rest-Activity Cycle, 2. the specific development of each physiological variable which is linked to the states, 3. the synchronization of these variables, and 4. the reduction of REM sleep time and the relative increase of non-REM sleep proportion. This ontogenetic scheme applies by in large to all mammals. It raises the fascinating question of the role of REM sleep and of dreaming in the evolution of the organism and of the species. PMID- 2919271 TI - [Menopause-osteoporosis: a challenge to modern society. Genova symposium (CRIS)]. PMID- 2919272 TI - [Evaluation of the ambulatory and hospital burden of patients with stage IV HIV infection]. AB - To evaluate the burden that AIDS patients will impose on health care facilities, we evaluated the costs incurred for patients with stage-IV HIV infection followed up at the Centre Hospitalier Universitaire Vaudois (CHUV) from 1982 to 1987. Besides determination of these costs the study shows that management of these patients is progressively switching from inpatient to outpatient services. In 1987; 0.25% of acute-care beds were occupied by patients with advanced HIV infection, and the inpatient cost for this new disease was estimated at approximately 700,000 Swiss francs. PMID- 2919274 TI - [Tamponade and central venous catheter. Apropos of a case]. AB - We report the case of a patient who developed cardiac tamponade after insertion of a central venous catheter. Often in such situations the first symptoms of this severe complication are late and thus delay correct diagnosis. In our patient the critical situation was recognized only after hemodynamic measurements and echocardiography. Emergency pericardiocentesis was followed by a dramatic improvement. The cardinal features of this serious event and the preventive measures to be taken to avoid this situation after placement of a central venous line are discussed. PMID- 2919273 TI - [Long-term oxygen therapy in Switzerland]. AB - In Switzerland long-term oxygen treatment is chiefly performed with oxygen concentrators provided by the Swiss Association against Tuberculosis and Pulmonary Diseases through its cantonal leagues. Prescription and supervision are carried out according to the Association's guidelines. To assess compliance with these guidelines, the prescription forms of 447 patients (1981-1985) were analyzed concerning diagnosis, lung function and blood gases. Of the 398 diagnoses mentioned, 73% were COPD, 16% restrictive syndromes and 11% cardiovascular diseases (including cor pulmonale). Lung function results were given in 81% of the total but in only 73% and 67% of two non-COPD groups. Blood gases at ambiant air were given in 92% and under oxygen at the flow chosen for treatment in 72%. At ambiant air the PaO2 was greater than 7.33 kPa in 21% (8.18 +/- 0.85 kPa) and less than 5.33 kPa in 19% (4.86 +/- 0.33 kPa). - These results show that prescription criteria are not always correctly met, especially in non COPD patients. They also suggest that long-term oxygen treatment is often prescribed mainly on the basis of clinical criteria, despite a PaO2 which would not require it, and also in unstable state, as indicated by the high proportion of cases with very low PaO2. The rationale behind the guidelines should be explained more clearly to prescribing doctors, in order to confine this difficult and costly treatment to patients who really need it. PMID- 2919275 TI - [The feeding of dogs in Switzerland. The results of an inquiry]. AB - Results of inquiry made of 2190 dog owners about customs of feeding and keeping dogs in Switzerland are presented. The diet most often used consists of cereal flakes which are given together with feedstuff from animals or other commercial dogfood. Usually, only one meal per day is given and the amount of food is based on a constant body weight. Regular feeding of bones appears to have a good effect on digestion and dental health. PMID- 2919276 TI - [What is your diagnosis? Sertoli cell tumor in a dog]. PMID- 2919277 TI - [Animal rights--new questions about animal ethics]. AB - The assertion that animals have interests and rights comparable to those of humans raises some new questions: How should unavoidable conflicts between man and animal be solved? How should a decision be taken in a conflict between human demands of no vital necessity e.g. the consumption of meat or mobility, and the right of animals to live? The answers to these questions illustrate the scope and limitations of ethical discussions. In spite of this solutions have to be elaborated based on conscience, ideas of a fair partnership and theological considerations. PMID- 2919278 TI - Navy marine mammals. PMID- 2919279 TI - Court ruling rekindles controversy over SATs. PMID- 2919280 TI - AIDS panel urges new focus. PMID- 2919282 TI - Frazier reinstated at McLean. PMID- 2919281 TI - Cancer Board attacks tobacco. PMID- 2919283 TI - Wanted: normal brains. PMID- 2919284 TI - New trial evaluates parkinsonian therapy. PMID- 2919285 TI - Epithelial cell surfaces induce Salmonella proteins required for bacterial adherence and invasion. AB - Salmonella bacteria are capable of entering (invading) and multiplying within eukaryotic cells. Stable adherence to and invasion of epithelial cells by S. choleraesuis and S. typhimurium were found to require de novo synthesis of several new bacterial proteins. This inducible event appears to be a coordinately regulated system dependent on trypsin- and neuraminidase-sensitive structures present on the epithelial cell surface. Mutants of S. choleraesuis and S. typhimurium were unable to synthesize these proteins and did not stably adhere to nor invade eukaryotic cells. Two such S. typhimurium mutants were avirulent in mice, an indication that these proteins are required for Salmonella virulence. PMID- 2919286 TI - Cancer in the elderly. PMID- 2919287 TI - Roferon-A in solid tumor therapy. PMID- 2919288 TI - The infant of the human immunodeficiency virus-infected mother. PMID- 2919289 TI - The AIDS epidemic: developing an institutional response. AB - The AIDS epidemic presents the health care delivery system with a number of diverse and complex challenges. Some institutions will perceive the problems associated with this disease as being overwhelming and insurmontable. Others will be stimulated by the scientific and ethical issues presented. The need to strike a balance, which incorporates the needs of the institution and the population to be served, cannot be stressed enough. The proper planning of an institutional response to this epidemic should involve an evaluation of internal resources, the investigation of existing models of AIDS care, and an assessment of the patient population. The departments of nursing, medicine, pediatrics, and social work can provide invaluable input into this process. Consultation with community-based agencies is also stressed, as these organizations provide an important source of supportive care to outpatients. A number of concerns are raised when institutions begin to plan and develop responses to the AIDS epidemic. These concerns often center on the perception that a visible commitment to persons with AIDS-related illnesses will keep other patients away or that attention and resources will be diverted from other equally serious conditions. Such concerns are reasonable and must be taken into account when planning any type of dedicated services. Particular care must be taken to avoid diverting resources from other programs. For institutions already providing care to large numbers of AIDS patients, the decision to centralize services and provide a more comprehensive approach to care is often a matter of relocation as opposed to introduction of a new patient care service.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2919290 TI - Psycho-social aspects of caring for families of infants infected with human immunodeficiency virus. PMID- 2919291 TI - Ethical issues in caring for pregnant women and newborns at risk for human immunodeficiency virus infection. PMID- 2919292 TI - Women infected with human immunodeficiency virus: counseling and testing during pregnancy. PMID- 2919293 TI - The radiographic appearances following adequate transfusion in beta-thalassaemia. AB - The main lesions of the skull and hand, observed in a group of hypertransfused beta-thalassaemic patients, are compared with a control group of low-transfused patients. Bony abnormalities reflect the relationship between proliferating bone marrow and bone cortex, and hypertransfusion therapy will prevent development of lesions only if established early in life. If this is done, the diploe in the skull may become normal, overgrowth of facial bone is moderate, pneumatisation of the paranasal sinuses is not completely prevented, and the "hair-brush" pattern may disappear completely. A normal appearance of the hand in adequately treated patients differentiates between prepubertal patients and adults. PMID- 2919294 TI - Micromelic bone dysplasia with cloverleaf skull. AB - Micromelic bone dysplasia with cloverleaf skull is a well-described entity with short, straight tubular bones, hydrocephalus and cloverleaf deformity of the skull, narrow chest and platyspondyly. A further two unrelated patients are presented, in whom the shape of the head varied. Both cases also showed a narrow foramen magnum, hypoplastic cerebellum, atrial septal defect, hypoplastic adrenals, and ureteric malformations. The findings in the skeleton show similarities to other types of generalised bone dysplasias but are distinguishable from these. This well-defined bone dysplasia should probably be regarded as a separate entity. Visceral malformations may be associated. PMID- 2919295 TI - Transverse posterior element fractures associated with torsion. AB - Six examples of a previously undescribed class of transverse vertebral element fractures are presented. These fractures differ from Chance and Smith fractures and their variants in the following respects: (1) the etiology is torsion and not flexion; (2) there is neither distraction of posterior ring fragments nor posterior ligament tears; (3) in contrast to Chance and Smith fractures, extension of the fracture into the vertebral body is absent or minimal; (4) the transverse process of the lumbar vertebra is avulsed at its base with a vertical fracture, not split horizontally. These fractures occur in cervical, lumbar, and sacral vertebrae in normal or compromised areas of the spine. PMID- 2919296 TI - Metaphyseal impaction fractures in acute lymphoblastic leukemia. AB - Patients with acute lymphatic leukaemia frequently are osteoporotic. A small subset of these develop disabling metaphyseal transverse fractures, usually bilateral and in the lower limb. These impaction fractures have a characteristic appearance and develop in recently laid down bone. They may develop ab initio or during therapy. Magnesium deficiency is found in these patients. PMID- 2919297 TI - Work in progress: postarthrography computed tomography of the wrist: evaluation of the triangular fibrocartilage complex. AB - This report reviews a work in progress evaluating the use of postarthrography computed tomography (CT) of the wrist in assessing triangular fibrocartilage complex abnormalities. Twenty-two triangular fibrocartilage complex perforations in 119 patients were identified with both multiple compartment arthrography and postarthrography CT. To obtain a double contrast image of the triangular fibrocartilage complex, the postarthrography CT examinations were performed after multiple compartment arthrography and the injection of air into the radiocarpal compartment. The site of triangular fibrocartilage complex perforation could be identified (radial versus peripheral) as could degenerative changes and internal derangements such as chondrocalcinosis. We did not, however, find any information not provided by arthrography that would have changed the course of management. At this time there is no clinical role for postarthrography CT in the evaluation of triangular fibrocartilage complex derangements. PMID- 2919298 TI - Stress views in the comparative assessment of spondylolytic spondylolisthesis. AB - Patients with spondylolytic spondylolisthesis were examined in six different positions to detect segmental instability. The amount of displacement was determined on lateral spot radiographs, taken in recumbent, standing, flexion, extension, axial compression, and traction positions in each patient. An error analysis was also performed. Examination in axial compression-traction was found to be a significantly better method for detection of segmental instability compared with standing-recumbent, or flexion-extension radiographs. In addition, the compression-traction method exhibited a higher sensitivity for identification of instability (73%) than standing-recumbent (33%) or flexion-extension (20%) views. The total error in the determination was small, +/- 2.5% (95% CL), providing a careful and controlled technique was used. PMID- 2919299 TI - The surgery of the rheumatoid wrist: postoperative appearances and complications of the more common procedures. AB - There is considerable orthopedic interest in the surgical management of rheumatoid arthritis involving the wrist. Surgery is being used more frequently in treating this condition, and many surgical options are available. The biomechanical basis, indications, postoperative appearances, and complications of these many operations should be known to the radiologist involved in preoperative care and postoperative follow-up. Some of the more frequent procedures are presented, and the complications are discussed. PMID- 2919301 TI - Requiem for the Eponym (Eponymomania). (For the International Skeletal Society). PMID- 2919300 TI - Rigid subtalar joint--a radiographic spectrum. AB - A painful or rigid subtalar joint is a common clinical problem. Computed tomography (CT) has been shown to be useful in evaluating tarsal coalition, but several other pathologic processes with a similar clinical presentation may affect the subtalar joint. Findings from 45 radiographically abnormal subtalar joints are presented, including examples of three different patterns of subtalar tarsal coalition, arthritis, infection, trauma and postsurgical changes. Knowledge of different causes of subtalar pathology may permit ready explanation of symptomatology related to the subtalar joint. PMID- 2919302 TI - Verbum sapienti. PMID- 2919303 TI - Case report 512: Spondyloenchondrodysplasia (SED) in two siblings. PMID- 2919304 TI - Case report 513: Tuberculosis of manubrium sterni. PMID- 2919306 TI - Case report 515: Simple (solitary) bone cyst of the calcaneus. PMID- 2919305 TI - Case report 514: Hamartomatous disorder (newly described). PMID- 2919307 TI - Case report 516: Lumbar vertebral chordoma causing sclerosis of affected vertebra (3rd lumbar vertebra). PMID- 2919308 TI - Case report 517: Ulcerating adamantinoma of the tibia. PMID- 2919309 TI - Catastrophic stress and factors affecting its consequences among Southeast Asian refugees. AB - Effects on mental health of the stress of being interned in a refugee camp were assessed in a community survey of 1348 Southeast Asians. The impact on depressive mood proved significant but short-lived. Social support derived from the ethnic community and from an intact marriage moderated the risk of developing depressive symptoms, apparently by enhancing a sense of identity and belongingness. A psychological coping mechanism--avoidance of the past--buffered the impact of camp stress on depressive symptoms. While refugees brought into the country under private sponsorship were expected to have a mental health advantage compared to those admitted under government sponsorship, this hypothesis was not confirmed. Private sponsorship, carried out by individuals or groups whose religion differed from the refugees they were supporting, acted as a source of stress. PMID- 2919310 TI - Survival of female breast cancer patients in Finland and in Estonia: stage at diagnosis important determinant of the difference between countries. AB - The survival experiences of female breast cancer patients diagnosed in 1968-81 in Finland and in Estonia were compared. The series consisted of 18,729 patients in Finland and 4100 in Estonia. The overall estimated 5-year relative survival rate was 67.3% in Finland and 55.9% in Estonia. The stage-adjusted 5-year relative survival rate in Estonia was 63.4% (the Finnish rates used as a standard). Older patients in Finland had much higher survival rates than older patients in Estonia. There was a clear difference in the stage distribution in Estonia between older and younger age groups, with non-localized cases occurring in older age groups. No such difference was noticed in Finland. It seems that the diagnostic lag for older women is longer in Estonia than in Finland. In Estonia older patients seek medical assistance later, or symptoms and signs of younger patients are more effectively studied. PMID- 2919311 TI - Psychosocial adjustment following a stroke. AB - A stroke can be a serious and debilitating health problem. The present study examined the effect of the severity of the stroke, patients' cognitive adaptation to their situation, the relationship with the caregiver and caregivers' adaptation on patient depression and motivation in outpatient therapy. Forty poststroke patients and their primary caregivers (usually a spouse) were interviewed an average of 9 months poststroke. Three independent predictors of depression were identified: a lack of meaningfulness in life, overprotection by the caregiver, and a less recent stroke. Motivation was independently related to less overprotection and lower perceptions of control over recovery. It was found that psychosocial factors predicted depression and motivation even when the effects of severity and site of the stroke were controlled for. The implications of cognitive adaptation and social support ideas for coping with a stroke are discussed. PMID- 2919312 TI - Role of support networks in maintenance of improved cardiovascular health status. AB - This study was undertaken to clarify the relationship between maintaining an improved cardiovascular health status and social support networks. Two hundred and ninety participants from a national trial that was carried out to specify the impact of reducing risk for cardiovascular disease were rescreened 3 years after completion of the trial. Original risk status of the participants was compared to risk status at the end to identify who had an improved risk status (n = 204). Risk status of 204 improvers was calculated from the rescreening data to identify maintainers (n = 63) and nonmaintainers (n = 143). No significant differences were found between maintainers and nonmaintainers in sociodemographic status, or in level of general support. Highly significant differences were found for four types of support provided specifically for risk reduction: information/advice (P = 0.002), appraisal (P = 0.004), emotional support (P = 0.01) and availability (P = 0.019). Most of these differences in support were accounted for by the larger support network identified by the maintainers. In addition, compared to nonmaintainers, maintainers' networks were more family-centered (P = 0.012), and were correspondingly more dense (P = 0.021). A discriminant function analysis using the significant variables was able to predict maintenance in 72% of the cases. The significant variables also accounted for 10% of the variance between maintainers and nonmaintainers. The implications of this study are: (1) assessment of support should be specific to the health outcome being studied: (2) research on the impact of social environment on health status will benefit from clearly specifying individual components of social support and social networks; (3) amount of social support provided is related to size of the network and relationship of supporter to the at-risk individual; (4) because social support and social networks account for a small but significant amount of the variance between maintainers and nonmaintainers, these concepts should be included in patient assessments prior to developing a treatment or maintenance plan. PMID- 2919313 TI - Employment of individuals with haemophilia in The Netherlands. AB - A study was performed to determine whether improvements in the treatment of haemophilia over the past 20 years have influenced the prospects of these patients in the labour market. Surveys on the medical and social situation of haemophiliacs in The Netherlands were carried out in 1972, 1978 and 1985. Most of the patients participated in these surveys. Trends in employment do not show either an increase in the number of employed haemophiliacs or a decrease in the number administratively defined as disabled. However, considering the influence of the economic recession on the position of the chronically sick on the labour market and the rise in the number administratively defined as disabled in the Dutch population, haemophiliacs perform well. Sick leave has decreased considerably. Although the employment rate for the group of haemophiliacs is lower than that for the general male population, the level of employment in relation to educational achievements is high and most of the employed do not feel limited in their daily job activities by the haemophilia. Physical mobility is a main factor influencing the employment status but other factors, such as the type of occupation or former occupation and prejudice against people with haemophilia, have to be considered. PMID- 2919314 TI - Breastfeeding trends in Singapore. AB - About 60% of well-to-do mothers in Singapore initiate breastfeeding. This value compares favourably with the 36% recently recorded for poor mothers, but is still unacceptably low compared to the 85-95% of well-to-do mothers and 90% of poor mothers who breastfed in the 1950s and 1960s. There has been a general decline in the incidence of breastfeeding over the last 35 years. Differences between the well-to-do and poor groups were initially small. A pronounced decline in the incidence of breastfeeding among the well-to-do mothers followed; a reversal in this downward trend in well-to-do mothers over the past 10 years has narrowed, and indeed reversed, the difference between the two groups. Similar trends can be found for the duration of breastfeeding. Whilst the overall decline probably reflects increasing affluence and 'Westernization' of the population the variation between these two economic groups is probably a result of differences in education. Among the three major ethnic communities, Chinese favoured breastfeeding least and Malays favoured it most. The differences are believed to be related to cultural differences and the ability of traditional practices and beliefs among the ethnic groups to resist the modern trend towards bottlefeeding. PMID- 2919315 TI - Determinants of fertility in a rural society: some evidence from Sierra Leone. AB - Data from a sample of 2000 currently married women aged 15-49 years, during a fertility and family planning survey carried out in rural areas of Moyamba District of Sierra Leone in 1979, are used to investigate the influences of background (wife's tribal and religious affiliations, and current place of residence), socio-economic (wife's education and occupation, and husband's education), and demographic (wife's current age, age at first marriage, desired family size, and infant-child mortality) variables on marital fertility in Sierra Leone. An OLS regression analysis indicates that the demographic variables, size of place of residence and wife's occupation affect fertility significantly. Wife's educational level and tribal affiliation exhibit marginal effects on fertility. Policy implications of these findings are discussed. PMID- 2919316 TI - Paternalism and Finnish anti-smoking policy. AB - Paternalism is one of the most problematic ethical issues in public health promotion. In the article an attempt is made to elucidate the matter by examining the theoretical characteristics of paternalistic attitudes and action on the one hand, and actual Finnish anti-smoking policies on the other. The attitudes adopted by Finnish health authorities toward smoking are strongly paternalistic, i.e. based on the idea that the general public is not to be relied on in assessing the health risks of tobacco use. Surprisingly, however, the actual governmental anti-smoking measures in Finland cannot be truthfully described as overtly constraining. Since paternalism implies restrictions on personal freedom for the individual's own good, many branches of smoking control fall outside its proper scope: for instance, restrictions on smoking in public premises can almost always be justified by referring to the harm inflicted by smokers on the other people. But most of the Finnish governmental anti-smoking measures which can be classified as paternalistic are also justifiable. Some of them concern minors only or mainly minors, and thus can be defended as instances of authorities' parental concern for our children. Some are freedom-restricting but only in a weak sense and are based on the idea of informing people about the dangers of smoking, while leaving the final decision up to them. In the last analysis, there is but one regulation that meets the criteria of wrongful paternalism, and that one, the ban on strong tobacco brands, may not be important enough, in practice, to raise major ethical controversies. PMID- 2919317 TI - [Double contrast pharyngography of dysphagia as a leading symptom. Methodology and diagnostic value]. PMID- 2919318 TI - [Thermoluminescent dosimetry of panoramic zonography]. PMID- 2919319 TI - [Radiotherapy planning: a barium sulfate-containing marker paste for computed tomography]. PMID- 2919320 TI - [A negative oral intestinal contrast medium for abdominal computed tomography]. PMID- 2919321 TI - Analgesic nitrous oxide for addictive withdrawal states. PMID- 2919322 TI - Paternity exclusion using 18 genetic systems in 2124 cases in four South African population groups. AB - Using 18 different blood group systems, 2,124 cases of doubtful paternity, unevenly distributed among four different population groups--South African Negroes (Xhosas) 645 (30%); South African Caucasians 264 (13%); Cape Coloureds (non-Malay) 1,156 (54%), and Cape Malays 59 (3%)--were analysed. Tests for red cell antigen, plasma protein, red cell enzyme and HLA polymorphisms were done on all subjects. The overall exclusion rate was 38,23%, i.e. 812 of the 2,124 men were not biological fathers of the children ascribed to them. The capability of the individual systems to exclude a man from specific paternity was also evaluated. The polymorphic HLA system was the most useful and alone--depending on the particular population group--excluded between 93.5% and 97.8% of falsely accused men. The proportion of men excluded also varied between different population groups using the different systems, e.g. the Rhesus system alone excluded 43.9% of South African Caucasian non-fathers and only 14% of the Xhosa non-fathers. This is a reflection of the gene frequencies within a particular population. The analysis showed that the genetic systems tested in this laboratory were extremely efficient in providing evidence in proof of non paternity. PMID- 2919323 TI - Morphometric analysis to detect suspected myocardial disease. A pilot study. AB - Myofibres in the normal left ventricle (LVs) of 24 healthy young accident victims and the diseased LVs of 10 subjects who died from constrictive pericarditis or congestive (African) cardiomyopathy were subjected to morphometric evaluation. Each myofibre was represented by a pair of measurements: cross-nuclear fibre (FD) and nuclear (ND) diameters. Using a VIDS image analyser interfaced with a light microscope, 150 paired measurements were determined for each of the 34 specimens. The bivariate relationship between FD and ND for each group of specimens were expressed as linear regressions. The limits for the group distribution of normal specimen FD/ND means were calculated and graphically depicted in the form of an ellipse. Disease specimens were plotted for comparison. Of the normal specimens, 23/24 FD/ND coordinates fell within the "normal' ellipse whereas the altered relationship between FD and ND in pathological myocardia caused all 10 specimen means to be plotted outside the ellipse and their regression lines to be displaced from normal. It is suggested that the normal data define the morphometric parameters of LV myofibres in healthy hearts and create a graphic standard by which myofibre pathology in hearts suspected of disease can be detected. PMID- 2919324 TI - Alcohol-related parasuicide among married people. AB - Although parasuicide has been widely studied, its indirect relationship with alcohol abuse has received less attention. The present study examines the incidence of alcohol-related parasuicide at a Pietermaritzburg general hospital. Over 40% of married parasuicide women cited their husbands' abuse of alcohol and its associated violent behaviour as precipitants to their self-destructive acts. However, in contrast to overseas findings, recent alcohol intake was not prevalent in the parasuicide women themselves. This difference appears to be culturally rooted. PMID- 2919325 TI - [Psychiatric aspects of family killings]. AB - There has been very little research done on family slayings in the RSA. The concept is defined and a short survey of the literature is provided. Five case studies of patients who were referred to Weskoppies Hospital after being involved in family killings are described; a diagnosis of depression was made in all 5 cases. The clinical implications of manslaughter and depression are discussed, and suggestions are offered for future research into psychiatric factors involved in family killings. PMID- 2919326 TI - Stannosis. A report of 2 cases. AB - Stannosis is a condition in which tin-oxide is deposited in lung tissue after inhalation. Tin-oxide is radiologically visible although there is no tissue reaction to its presence. Two examples of the condition are described. It is of value to recognise the condition and so avoid unnecessary invasive diagnostic procedures. PMID- 2919327 TI - The role of the clinical health psychologist in the management of chronic paediatric illness. A report of 2 cases. AB - Behavioural problems in chronically ill children are common and adequate provision for holistic management is necessary. It appears preferable for psychological intervention to start not when the child is referred with behavioural problems but as soon as the medical condition is diagnosed. These children, and their families, are usually in need of psychological care from the earliest stages of the disease process. Two case reports are cited in this context. The role of the clinical health psychologist is emphasised. PMID- 2919328 TI - Pulsed Doppler and two-dimensional echocardiographic findings in coronary arteriovenous fistula complicated by bacterial endocarditis. A case report. AB - Coronary arteriovenous fistula (CAVF) may occasionally be complicated by bacterial endocarditis. The actual anatomical site of infection has not been clearly defined. A 13-year-old boy with a CAVF and Streptococcus viridans bacteraemia is described. The origin of the fistulous tract and a vegetation in close proximity to the distal drainage site into the right ventricle was demonstrated by Doppler two-dimensional echocardiography. PMID- 2919329 TI - Temporal lobectomy in epilepsy. A report of 2 cases. AB - Two South African patients with frequent drug-resistant complex partial seizures arising from the left temporal lobe were referred to the UK for anterior temporal lobectomy. Both patients are now seizure-free, the first 3 1/2 years and the second 2 1/2 years after operation. Clinical details are presented. PMID- 2919330 TI - Legionella pneumonia--a need for epidemiological alert. PMID- 2919331 TI - Small is beautiful. PMID- 2919332 TI - Port-a-Cath--a totally skin-covered venous access system for long-term cytotoxic treatment. PMID- 2919335 TI - The haematology of tuberculosis. PMID- 2919334 TI - Cardiac biopsy. PMID- 2919333 TI - Antibody to HTLV-I in a black South African with a neurological disorder resembling multiple sclerosis. PMID- 2919336 TI - Blood transfusion in the newborn infant. PMID- 2919337 TI - Priorities for research on smoking and health. PMID- 2919338 TI - Mononuclear leucocyte function in patients with lichen planus and cutaneous lupus erythematosus during chemotherapy with clofazimine. AB - Mitogen-induced transformation and the production of reactive oxidants by mononuclear leucocytes (MNLs) from patients with chronic dermatological disorders were investigated in vitro before and during the administration of the antimycobacterial/immunosuppressive agent clofazimine (200 mg 3 times weekly). Seven patients, 4 with lichen planus and 3 with cutaneous lupus erythematosus, were included in the study. Clofazimine administration did not influence the mitogen-induced proliferative responses of patients' MNLs. However, chemotherapy with this drug stimulated the production of reactive oxidants by MNLs. Since reactive oxidants are immunosuppressive it is possible that these effects may be involved in the pharmacotherapeutic activity of clofazimine. PMID- 2919339 TI - Consecutive melatonin circadian rhythms in normal volunteers. AB - Circadian plasma melatonin secretion patterns were determined in 12 healthy men over 3 consecutive 24-hour periods. The rhythms showed marked intra-individual stability, but pronounced interindividual variation. Plasma melatonin may serve as a reliable biological marker. Plasma melatonin assayed between 23h00 and 01h00 gave a reliable indication of an individual's circadian melatonin rhythm. PMID- 2919340 TI - Disease profiles for white and black adult and geriatric patients. An analysis of 2,008 hospital medical admissions. AB - A prospective analysis of 2,008 discharge diagnoses revealed important differences in disease incidence between black and white adult and geriatric patients treated in the Department of Medicine, Frere Hospital, East London. Among geriatric patients the major differences were the increased incidences among blacks of tuberculosis, pulmonary circulatory disorders and cardiomyopathy, as opposed to ischaemic heart disease, cerebrovascular disorders and chronic obstructive pulmonary disease among whites. Among blacks hypertension was less common than had been expected and occurred predominantly in females. Tuberculosis affected 14% of blacks but only 1.6% of whites. It was also the commonest cause of medical deaths and responsible for 31% of deaths of black patients. Analysis of age patterns showed that 68% of whites and 31% of blacks were over 60 years old; 18% of whites and 3% of blacks were over 80 years old. These figures indicate the need to extend hospital facilities for geriatric patients, and for more comprehensive training in geriatric medicine for doctors and nurses. PMID- 2919341 TI - Euthyroid hyperthyroxinaemia due to endogenous antibodies to thyroxine and tri iodothyronine. A case report. AB - A case of euthyroid hyperthyroxinaemia caused by auto-antibodies to thyroxine and tri-iodothyronine is presented. Gel filtration chromatography of the patient's serum showed increased binding of radio-labelled thyroxine analogue to a macromolecular component, which migrated in the gammaglobulin region on electrophoresis. Precipitation by protein A confirmed that this was an immunoglobulin. The importance of recognising this condition so that inappropriate therapy can be avoided is stressed. PMID- 2919342 TI - Partial hydatidiform mole with a coexistent live full-term fetus. A case report. AB - A patient with a partial hydatidiform mole, who had a coexistent normal fetus, is described. The pregnancy proceeded to term and ended in the spontaneous, vaginal delivery of a normal baby. The placenta showed areas of macroscopic cystic degeneration with the histological features of hydatidiform mole. PMID- 2919343 TI - Listeria pneumonia. A case report. AB - A 42-year-old man with an atypical pneumonia. He had chest pain and a dry cough for 3 weeks, was dull at the left base clinically, and had left lower zone consolidation on chest radiography. The pneumonia spread despite oral ampicillin and cloxacillin. Blood culture grew Listeria monocytogenes and white cell count showed a monocytosis. He responded to intravenous penicillin and gentamicin with complete X-ray clearance. PMID- 2919344 TI - Tuberculous paraplegia during pregnancy. A report of 4 cases. AB - Four patients who developed tuberculous paraplegia during pregnancy are described. They delivered at term without complications and then underwent successful decompression for paraplegia. PMID- 2919345 TI - Antibiotic sensitivity of pathogenic bacteria in cutaneous infections in the Johannesburg area. PMID- 2919347 TI - Occupational hazards and health workers. PMID- 2919346 TI - Evaluation of lung function in uranium mine workers. PMID- 2919348 TI - Continuous insufflation of the pharynx in oropharyngeal obstruction. PMID- 2919349 TI - Pulmonary tuberculosis in geriatric homes in Port Elizabeth. PMID- 2919350 TI - Birth by days of the week. PMID- 2919351 TI - Differences in cardiac responses to resuscitation from burn shock. AB - Isolated coronary perfused hearts from guinea pigs were used to determine if aging alters left ventricular (LV) intrinsic contractile response to resuscitated burn shock. Parameters measured included LV pressure (LVP) and maximal rate of LVP rise (+dP/dt max) and fall (-dP/dt max) at a constant preload (LV enddiastolic pressure [LVEDP]). Compared with young controls (ten), aged control hearts (ten) showed significantly lower LVP (87.4 +/- 2.53 versus 76.0 +/- 1.5, p,0.001), +dP/dt max (1,351 +/- 51 versus 1,048 +/- 49, p,0.001), and -dP/dt max (1,154 +/- 34 versus 916 +/- 27, p,0.001), at an LVEDP of 10 millimeters of mercury. A 43 +/- 2 per cent third-degree burn (Walker model) was studied in ten young and ten aged guinea pigs. Burned aged hearts showed significantly lower LVP (57.1 +/- 2.1 versus 67.5 +/- 3.7, p,0.01) and -dP/dt max (707 +/- 33 versus 993 +/- 59, p,0.001) at an LVEDP of 10 millimeters of mercury. In addition, LV function curves for burned aged hearts were shifted downward and to the right of curves obtained from young burned hearts (p,0.05). Contractile defects in the aged group were not overcome by altered beating frequency, increased extracellular calcium concentration, nor maximally effective increases in diastolic stretch. Finally, we examined the effects of fluid resuscitation (4 milliliters per kilogram per percentage of burns) on contractile function in an additional ten young and ten aged burned guinea pigs. Contractile deficits persisted in both age groups despite adequate fluid resuscitation. Peak LVP and maximal rate of relaxation (-dP/dt) were uniformly depressed in aged as compared with young burned hearts (52.4 +/- 1.5 versus 63.2 +/- 2.7 and 715 +/- 42 versus 909 +/- 52, p,0.01, respectively). These data suggest that severe myocardial contractile change resulting from a major thermal insult in subjects with already compromised hearts is likely a significant limiting factor in the response to burn shock and adequate fluid resuscitation. PMID- 2919352 TI - Second look operation in managing carcinoma of the pancreas and periampullary region. AB - From a total of 153 patients with carcinoma of the periampullary region and of the head of the pancreas, 127 underwent surgical treatment. There were 79 men and 48 women with a mean age of 65 years (a range of 39 to 90 years). Of these, 26 had resectional operations. Fifteen were carried out at the initial laparotomy and 11 at a second look operation (SLO). Of the 112 patients who had a palliative bypass at the initial laparotomy, 30, who were less than 65 years of age and were fit and remained so when assessed at six and 12 weeks postoperatively, were re evaluated for SLO. Of these, 12 had evidence of metastases and, therefore, were not considered for SLO. Eleven had a successful resection, and in seven, attempted resection had to be abandoned because of local invasion. The five year survival rate was 50 per cent for carcinoma of the periampullary region and 9 per cent for carcinoma of the head of the pancreas after primary resection. The comparable rates after SLO were 33.3 and 12.5 per cent, respectively. Based on our experience, SLO should be considered in young, fit patients as associated pancreatitis can make some tumors seem locally invasive and, hence, appear unresectable at the initial laparotomy. PMID- 2919353 TI - Quantitative evaluation of stiffness of commercial suture materials. AB - The bending stiffness of 22 commercial suture materials of varying size, chemical structure and physical form was quantitatively evaluated using a stiffness tester (Taber V-5, model 150B, Teledyne). The commercial sutures were Chromic catgut; Dexon (polyglycolic acid); Vicryl (polyglactin 910); PDS (polydioxanone); Maxon (polyglycolide-trimethylene carbonate); Silk (coated with silicone); Mersilene (polyester fiber); Tycron (polyester fiber); Ethibond (polyethylene terephthalate coated with polybutylene); Nurolon (nylon 66); Surgilon (nylon 66 coated with silicone); Ethilon (coated nylon 66), Prolene (polypropylene); Dermalene (polyethylene), and Gore-tex (polytetraflouroethylene). These are both natural and synthetic, absorbable and nonabsorbable and monofilament and multifilament sutures. All of these sutures were size 2-0, but Prolene sutures with sizes ranging from 1-0 to 9-0 were also tested to determine the effect of suture size on stiffness. The bending stiffness data obtained showed that a wide range of bending stiffness was observed among the 22 commercial sutures. The most flexible 2-0 suture was Gore-tex, followed by Dexon, Silk, Surgilon, Vicryl (uncoated), Tycron, Nurolon, Mersilene, Ethibond, Maxon, PDS, Ethilon, Prolene, Chromic catgut, coated Vicryl, and lastly, Dermalene. The large porous volume inherent in Gore-tex monofilament suture was the reason for its lowest flexural stiffness. Sutures with a braided structure were generally more flexible than those of a monofilament structure, irrespective of the chemical constituents. Coated sutures had significantly higher stiffness than the corresponding uncoated ones. This is particularly true when polymers rather than wax were used as the coating material. This increase in stiffness is attributable to the loss of mobility under bending force in the fibers and yarns that make up the sutures. An increase in the size of the suture significantly increased the stiffness, and the magnitude of increase depended on the chemical constituent of the suture. The flexural stiffness of sutures was also found to depend on the duration of bending in the test for stiffness. In general, monofilament sutures exhibited the largest time-dependent stiffness. This was most pronounced with the Gore-tex suture. Most braided sutures also showed less time-dependence in stiffness. Nylon sutures did not exhibit this time-dependent phenomenon regardless of physical form. PMID- 2919354 TI - Juvenile malignant melanoma. AB - Malignant melanoma in children and adolescents is a rare phenomenon. During a retrospective computer-aided chart review, 78 patients less than 20 years of age were identified who had the diagnosis of malignant melanoma. This accounted for 1.8 per cent of all the melanomas registered at the University Melanoma Clinic. Fifty-one per cent were females, and all the patients were white. Most of the lesions were found on the primary areas of the trunk and extremities. Sixty-seven per cent of the melanomas were of the superficial spreading type, and 82 per cent were invasive to Clark level III and IV. The range of tumor thickness was 0.32 to 5.22 millimeters, with a mean of 1.76 millimeters. Similar population characteristics were noted in the adult and juvenile populations. Controlling for the two most powerful prognostic factors for Stage I melanoma, that is, ulceration and tumor thickness, the actuarial survival times between the two population groups were similar. The median survival times in the adult and juvenile population were 12.9 and 11.9 years, respectively (p = 0.54). There was a trend toward a shorter disease-free interval in the juvenile population. The five year disease-free interval was 65 per cent for adults with melanoma compared with 57 per cent for juveniles with malignant melanoma (p = 0.16). Multiple regression analysis failed to reveal age less than 20 years to be an independent prognostic factor for the development of metastases or over-all survival time. Recurrent disease was observed in 46.2 per cent of juveniles with melanoma who were initially Stage I at diagnosis. Eighty per cent of the relapses occurred in either the local skin or regional lymph nodes. Although malignant melanoma is rare in populations of patients younger than 20 years of age, clinicians should be aware that melanoma does occur in juveniles. With an aggressive approach to surgical therapy, survival rate is comparable with that of the adult population. PMID- 2919355 TI - Abstract renders the summary superfluous. AB - By definition, an abstract and summary must contain much the same content, as it is the purpose of each to provide a synopsis of the study or review. The journal Surgery Gynecology and Obstetrics requires both an abstract and a summary for its articles. We studied 83 reports from Surgery, Gynecology and Obstetrics, reviewing the similarities and differences in the abstracts and summaries based on six objective criteria: the number of words, the number of sentences, the number of repetitious sentences, the clarity of the abstract or summary without having to refer to the body of the article, the expression of conclusions and the introduction of new material that is not mentioned within the body of the article. Our results showed that, although abstracts were nearly one-third longer than the summaries, almost one-third of the sentences were repetitious. On the other hand, in one-fifth of the instances, the important conclusions of the article were included in either the abstract or summary but not both. We conclude that the quantitative and structural attributes of the summary and abstract are sufficiently similar to warrant that the abstract mandated by many publications has rendered the summary superfluous. Furthermore, when both the abstract and summary are included within an article, the omission of important conclusions can occur in one or the other. We recommend to retain the abstract or the summary in the conventional format in the articles rather than to have both in entirety or an altered format. PMID- 2919356 TI - A simple method for controlling hemorrhage during hepatectomy. AB - A technique of compressing the liver parenchyma without interfering with the blood supply to the remainder of the liver during anatomic and nonanatomic resections is presented. Two grooved nylon strips fitted into each other to form an ellipse that is tightened near the resection line permits the parenchymal incision in an unhurried and practically bloodless manner. PMID- 2919357 TI - Splenorenal anastomosis during resection of juxtarenal aortic aneurysm. PMID- 2919358 TI - An improved technique for rapid infusion of warmed fluid using a Level 1 Fluid Warmer. PMID- 2919359 TI - Quantification of abnormal intracranial pressure waves and isotope cisternography for diagnosis of occult communicating hydrocephalus. AB - Nineteen consecutive patients with suspected occult communicating hydrocephalus were investigated by means of clinical evaluation, neuropsychological testing, isotope cisternography, computed tomography scanning, and continuous intracranial pressure monitoring. Semi-quantitative grading systems were used in the evaluation of the clinical, neuropsychological, and cisternographic assessments. Clinical examination, neuropsychological testing, and computed tomography scanning were repeated 3 months after ventriculoperitoneal shunting. All patients showed abnormal intracranial pressure waves and all improved after shunting. There was close correlation between number, peak, and pulse pressures of B waves and the mean intracranial pressure. However, quantification of B waves by means of number, frequency, and amplitude did not help in predicting the degree of clinical improvement postshunting. The most sensitive predictor of favorable response to shunting was enlargement of the temporal horns on computed tomography scan. Furthermore, the size of temporal horns correlated with mean intracranial pressure. There was no correlation between abnormalities on isotope cisternography and clinical improvement. PMID- 2919360 TI - Pituitary adenoma with multiple ciliated cysts: transitional cell tumor? AB - The case of a prolactin-secreting pituitary tumor with multiple cyst formation is described. Ultrastructurally, the cyst-lining cells were ciliated and closely resembled those of Rathke's cleft cyst but contained secretory granules, and no basal lamina formation was seen between the adenoma cells and the lining cells. Immunohistochemical study revealed that the adenoma cells consisted of both prolactin-secreting cells and growth hormone-secreting cells. The lining cells were immunoreactive with the antiserum to cytokeratin. No S-100 protein-positive cells were seen. The origin of this tumor is discussed. PMID- 2919361 TI - Radical surgery of a galenic aneurysm with regional cerebral blood flow analysis. A case report. AB - Successful surgical treatment of a case of aneurysm of the vein of Galen is presented. An 11-month-old boy was admitted with episodes of convulsive attacks. Neuroradiological examination revealed an aneurysm of the vein of Galen filled by branches of posterior cerebral arteries and left thalamoperforating artery. Regional cerebral blood flow, which was measured by a method of xenon-enhanced computed tomography, showed a low flow area in the frontal and occipital regions. The aneurysm was approached through the bilateral parietooccipital interhemisphere, freed from the feeders, and ligated. During the operation, cortical blood flow was monitored for prevention of normal perfusion pressure breakthrough. After the feeders were successfully clipped, the blood flow increased and became normalized in the related cortex. There was no postoperative neurological deterioration. PMID- 2919362 TI - Brain tolerance to middle cerebral artery occlusion during hypotension in primates. AB - The aim of this study was to determine the duration of middle cerebral artery occlusion required to produce significant ischemic damage when the occlusion occurs during controlled systemic hypotension. In 21 anesthetized cynomolgus monkeys, an IV infusion of sodium nitroprusside was used to lower the mean arterial blood pressure to 45-50 mmHg for 90 minutes. Middle cerebral artery occlusion for 15, 30, 45, or 60 minutes was performed during the hypotensive period. Neurological function was then evaluated every 8 hours for a total of 72 hours. At the end of the observation period, the monkeys were again anesthetized, magnetic resonance imaging was performed, and the brain was perfused with 10% buffered formalin. Neurological deficits were observed after 30 minutes, but not after 15 minutes, of middle cerebral artery occlusion, and rapidly increased in incidence and severity when the duration of occlusion was increased. After 60 minutes of occlusion, all the monkeys exhibited severe deficits. Four monkeys died during the observation period--two in each of the 45- and 60-minute occlusion groups. Histopathological examination revealed that little or no ischemic damage resulted from a 15-minute occlusion during hypotension. However, severe ischemic damage began to occur after only 30 minutes of occlusion, and all monkeys subjected to middle cerebral artery occlusion for 60 minutes developed extensive regions of infarction. The size and incidence of these infarctions correlated well with the lesions observed in the magnetic resonance images. These results demonstrate that the duration of middle cerebral artery occlusion that produces cerebral infarction in primates is drastically reduced when the occlusion occurs at hypotensive levels commonly employed during neurovascular surgical procedures. PMID- 2919363 TI - Intramedullary cavernous angiomas. AB - Two cases of histologically verified intramedullary cavernous angiomas at C3 and D5-6 are presented. Both patients suffered progressive myelopathy with intermittent improvement. In both cases preoperative diagnosis was possible by means of magnetic resonance imaging using spin echo techniques, fast imaging, and phase display, while spinal angiography was not helpful. Laminectomy and total removal of the tumors were performed with temporary increased neurological deficits. It is thought that magnetic resonance imaging provides a useful diagnostic tool in these tumors and is also essential for planning surgical strategy. PMID- 2919364 TI - Convexity meningioma with galactorrhea and hyperprolactinemia. A case report. AB - A case is reported of a huge convexity meningioma associated with galactorrhea and an elevated serum prolactin level of 41 ng/mL. Total removal of the tumor resulted in a return of the prolactin level to normal (9.7 ng/mL). Because of a severe mass effect, the distant tumor might have encroached upon the hypothalamic pituitary axis and interrupted PRL inhibitory factor regulation. PMID- 2919365 TI - "Perjury is not a crime". PMID- 2919366 TI - Society of University Surgeons: present and future horizons. PMID- 2919367 TI - Serotoninergic neurites in senile plaques in cingulate cortex of aged nonhuman primate. AB - In immunocytochemical studies, a polyclonal antiserotonin antibody was used to visualize fibers within the cingulate cortex of young and aged rhesus monkeys. Intricate and distinct patterns of serotoninergic processes were seen in anterior and posterior segments of cingulate cortex (Brodmann areas 24 and 23). In these regions of cortex, many multivaricose serotonin-immunoreactive axonal swellings were identified, and some of these immunostained neurites were associated with deposits of amyloid. These observations suggest that serotoninergic processes are involved in the formation of senile plaques in neocortex of aged macaques. PMID- 2919368 TI - Presence of ghost doublets of coded neuronal patterns: relation to synaptic memory storage. AB - Recent evidence demonstrates that controlled visual stimuli cause the generation, in the primary visual cortex of rhesus monkey cells, of large numbers of very precisely replicating copies of complex patterns of discharge consisting of three or more spikes, the patterns of which presumedly code for specific qualities of the stimuli presented. We present evidence that the copies of precisely replicating triplets of spikes, generally not exceeding 100 ms in duration, occur in close time proximity to many copies of highly precise "ghost" doublets. These doublets are defined as patterns consisting of two pulses, with precise separations in time, specifically those that would be generated if any one of the pulses making up a given replicating triplet were missing. In striking contrast, nonreplicating triplets (also present in these records)--that is, triplets made up of intervals that are not present in replicating triplets--are not accompanied by such ghost doublets. The persistence (memory) of capacity to produce such ghost doublets decays according to two independent kinetic rules. The first of these results in the disappearance of such doublets within about 0.1 s as measured by two independent methods, whereas the second disappears only after several minutes or longer. These results provide strong evidence consistent with the notion that at least some parts of the brain transmit, store representations of, and retrieve qualitative information through the use of a code consisting of specific patterns of nerve discharges in time. PMID- 2919369 TI - Chloral hydrate anesthesia alters the responsiveness of identified midbrain dopamine neurons to dopamine agonist administration. AB - Single-unit electrophysiological recording techniques were used to sample the basal activity of antidromically identified nigrostriatal and mesoaccumbens dopamine (NSDA and MADA, respectively) neurons and to examine the responsiveness of these cells to dopamine agonist-induced inhibition of cell firing rate in either chloral hydrate-anesthetized or paralyzed rats. Paralyzed rats exhibited a greater percentage of burst-firing cells (69%) than did anesthetized animals (37%). Furthermore, paralyzed rats were less sensitive to the mixed D1/D2 DA receptor agonist apomorphine and the selective D2 DA receptor agonist quinpirole. However, significantly higher doses of d-amphetamine were required in paralyzed animals only with respect to inhibiting MADA neurons. The abilities of apomorphine and quinpirole to inhibit NSDA cell firing were rate-dependent in both anesthetized and paralyzed rats, whereas d-amphetamine-induced inhibition was rate dependent only in anesthetized animals. In contrast, apomorphine- and quinpirole-induced inhibition of MADA neurons were rate-dependent only in anesthetized rats, whereas d-amphetamine-induced inhibition was rate-dependent only in paralyzed animals. These results suggest that general anesthesia exerts subtle effects on the basal activity and pharmacological responsiveness of midbrain dopamine neurons. PMID- 2919370 TI - Afferent axons from the antenna influence the number and placement of intrinsic synapses in the antennal lobes of Manduca sexta. AB - The present study compares the placement and frequency of occurrence of synapses in normally developing antennal lobes of the brain of the moth Manduca sexta and in lobes developing in the absence of afferent axons from the antenna. The antennal lobes develop during the metamorphosis from larva to moth, and require antennal afferent input to develop their characteristic knots of synaptic neuropil, the glomeruli, that are arrayed around a central core of coarse neuropil. Synapses begin to form throughout the neuropil of the antennal lobe before ingrowth of antennal axons into the lobe. During normal development, almost all synapses (those among intrinsic neurons as well as those made by antennal afferent axons) become segregated into glomeruli as the glomeruli are established. Thus, in normal mature lobes, the radial segregation between synaptic (glomerular) and nonsynaptic (central) regions is virtually complete. In lobes that have never been allowed to receive antennal axons, an outer ring of "protoglomerular" neuropil develops in place of the glomeruli. A similar segregation of synaptic and nonsynaptic regions occurs, with two major differences: the frequency of synapses that develops in the outer ring of fine textured neuropil is almost 50% higher than in normal glomeruli, and the small number of synapses that occur in the coarse central neuropil now occur on aberrant fine processes in that neuropil. Apparently, in the absence of their normal massive input from the antenna, elements intrinsic to the antennal lobe are induced to form extra synapses with each other, and to send aberrant fine branches to synapse in a region of neuropil normally containing predominantly large-caliber neurite trunks and few synapses. PMID- 2919371 TI - [Health care for the mentally retarded--special care. Consequences of liquidation]. PMID- 2919372 TI - [A study of new patients at a dermatologic outpatient clinic]. AB - Data on all new dermatology outpatients seen during the period 1 January to 30 June 1987 were analyzed in order to obtain information on the types of patients attending the clinic and on the skin diseases presented. We also recorded the source of referral, the frequency of the need for surgery, and patient compliance. There was a general predominance of female patients (60%), particularly in the 21-30 years age group. The leading diagnoses were atopic dermatitis (18%) and psoriasis (11%), and 2/3 of the atopic dermatitis patients were female. A skin biopsy was performed in 12% of the new patients and the clinical pre-biopsy diagnosis was correct in 72% of the cases. Surgery was necessary in 16% of all new patients. 54% of the patients required a follow-up appointment. 11% of these (108 patients) failed to appear. Patients with atopic dermatitis were the chief offenders in this latter group. The results of the study suggest that out-patient costs and waiting lists could be reduced by revising the indications for biopsy and follow-up appointments. PMID- 2919373 TI - [Cytogenetic analysis in acute leukemia]. AB - Leukemic cells often show clonal cytogenetic abnormalities. Some of these are strongly associated with certain morphological subgroups and seem to be of prognostic importance. Cytogenetic studies and molecular genetic investigations using recombinant DNA technology have contributed to our understanding of the development of leukemia. This article reviews earlier work on cytogenetic findings in acute leukemia, and adds our own experiences. PMID- 2919374 TI - [Experiences of immunologic phenotyping in acute leukemia]. AB - Phenotyping of leukemic cells with monoclonal antibodies usually confirms the morphological classification in acute lymphoblastic and acute myeloid leukemia. Immunological phenotyping gives a more detailed subclassification and may add information on the stage of differentiation of the leukemic cells. This may have prognostic implications, and in the future may influence the choice of treatment modalities. It is not unusual for the leukemic cells to carry both myeloid and lymphoid markers. For such leukemias the prognosis is poor. We describe our experience from immunological phenotyping of 46 acute myeloid and 35 acute lymphoblastic leukemias. PMID- 2919375 TI - [Viral or bacterial meningitis. Differential diagnostic problems]. AB - A 19 year old previously healthy man presented symptoms of meningitis. Culture from the cerebrospinal fluid revealed herpes simplex virus type 2 to be the responsible agent. The course was benign, the patient was never seriously ill. He recovered fully within a few weeks. The cerebrospinal fluid showed prolonged pleocytosis and low values of glucose. The traditional cerebrospinal fluid parameters employed in the diagnosis of meningitis, and for distinguishing bacterial from viral meningitis, are shown to be inadequate in many cases. Of these tests cerebrospinal fluid differential cell count is of most value, especially if repeated after 12 hours or so in the initial course. Additional tests have been proposed, none of which have proven to be of much help, except perhaps the test for lactate in the cerebrospinal fluid. PMID- 2919376 TI - [Herpes simplex virus infection of the central nervous system]. AB - Herpes simplex virus type 1 (HSV 1) infection in the central nervous system results in encephalitis with high mortality and morbidity. However herpes simplex virus type 2 (HSV 2) infection in this area usually results in benign meningitis. Brain biopsy is the most sensitive and most specific method for diagnosing HSV 1 encephalitis. Antibody determinations in serum and cerebrospinal fluid give only a retrospective diagnosis. A rapid non-invasive diagnostic test is urgently required as an alternative to biopsy. Cerebrospinal fluid viral culture may be of great help in diagnosing HSV 2 meningitis. Acyclovir given intravenously is the treatment of choice for HSV encephalitis. In the case of HSV 2 meningitis no studies have been conducted on systemic antiviral therapy. PMID- 2919377 TI - [Pathologic brain damage in male alcoholics dying outside of hospitals]. AB - From 1984 to 1988, 195 male alcoholics aged 30-64 years who died outside hospitals and nursing homes in Oslo were autopsied at the Institute of Forensic Medicine, the National Hospital, Oslo. Of the 127 brains neuropathologically examined, 86 (67.7%) showed abnormalities, and 28 contained lesions of more than one type. One or two lesions associated with alcoholism were found in 61 cases (48%). Thus, 18 (14.2%) showed Wernicke's encephalopathy, 47 (37%) cerebellar atrophy, two central pontine myelinolysis, and one hepatic encephalopathy. Subdural haematoma and/or cortical contusions were found in 30 (23.6%), and cerebrovascular lesions in 19 (15%). Of the 195 cases, 22 had a history of repeated epileptic seizures. Nineteen of them were examined neuropathologically, and 13 had focal damage that might have been responsible for their fits. The results indicate that the frequency of Wernicke's encephalopathy and cerebellar atrophy in male alcoholics who die outside hospital is similar to that previously observed in cases who died in hospital. Although cerebral damage was even more frequent among vagrants and others dependent on social support, half the men living in their own homes were also affected. PMID- 2919378 TI - [Alcohol-induced hyperlipemia. Hypertension and extreme hypercholesterolemia/hypertriglyceridemia in a patient with hidden alcohol abuse]. AB - The article presents the case history of a 28 year-old male with alcohol-induced hypertension and extreme hypercholesterolemia (36 mmol/l) and hypertriglyceridemia (76 mmol/l). Blood pressure and blood lipids were completely normalized after a few months withdrawal from alcohol. Alcoholism is emphasized as a possible differential diagnosis for both hypertension and hyperlipemias. The upper referential value for alcoholic hyperlipemia should probably be adjusted in accordance with the values observed in the present case. PMID- 2919379 TI - [Retinopathy as a complication of acute pancreatitis]. AB - We describe a case of acute, severe retinopathy in a patient with acute pancreatitis. The relative times of the organ manifestations, and comparisons with other published cases, strongly suggest that the pancreatitis was the cause of the retinal changes. This complication is unknown to most physicians, but ten to 12 cases have been published earlier. The pathogenesis is not known. We briefly discuss the significance of this complication and several possible pathogenetic mechanisms. PMID- 2919380 TI - [Intestinal spirochetes]. AB - We report a case of intestinal spirochaetosis. The bacteria were seen by light microscopy and reacted in an indirect immunofluorescence test on the biopsy material with serum with high levels of IgG antibodies against Borrelia burgdorferi. The patient's own serum had no detectable antibody activity against the bacteria. No inflammatory response was observed. Aspects of these findings are discussed. PMID- 2919381 TI - [Hypercholesterolemia. Use of laboratory analysis]. AB - The article summarizes the use of laboratory analysis as described in the recently published Norwegian program for diagnosis and treatment of hypercholesterolemia in adults. Serum cholesterol is used both to diagnose hypercholesterolemia and to monitor the effect of treatment. Serum triglycerides should be measured when hypercholesterolemia has been found and dietetic treatment is considered. High density lipoprotein (HDL) cholesterol should be measured when dietetic treatment has not reduced hypercholesterolemia sufficiently and drug treatment is considered. We do not at present recommend measurement of apolipoproteins and factors within coagulation/fibrinolysis, but such measurements might be of importance in the near future. Blood cholesterol exhibits large biological variations, which makes retesting necessary before hypercholesterolemia is diagnosed. Analytical variation is usually less than biological variation, but requires use of quality control materials. This control is equally important for small dry chemistry analyzers as for wet chemistry analyzers. PMID- 2919382 TI - [Treatment of diarrhea in children]. PMID- 2919383 TI - [The general population as a reference group. A discussion of the concept of the healthy worker effect]. AB - In cohort studies concerning occupational diseases the general population is a commonly used reference entity in countries with national cancer registries or census bureaus. However, former and present employees regularly experience lower disease incidence than the general population, even in occupations with exposures known to cause adverse health outcomes. This phenomenon is often referred to as the "healthy worker effect". The concept is discussed in the present paper. PMID- 2919384 TI - [Who is left in the institutions? Some problems in connection with the process of deinstitutionalization]. AB - The medical and psychiatric diagnoses of 168 clients aged 16 to 65 years in a Norwegian institution for the mentally retarded were registered together with medication, level of functioning, and types of problem behavior. Most of these clients (64.9%) were profoundly or deeply retarded, and only 6.5% were independent of continuous supervision or help. Medical diagnoses were found in 87.5%, psychiatric diagnoses in 89.1% (DSM-III, axis I). Daily use of medication was found in 81.0% of the clients, and 48.9% used psychotropic drugs on a daily schedule. 58.3% of the clients had exhibited violent behavior during the last year, defined as assaults on persons, self-mutilation or destructiveness. The article discusses the implications of these observations for primary health care, which is expected to supply the necessary service to these clients after 1991. PMID- 2919385 TI - [Psychosocial gynecology and obstetrics. A need for its own specialty]. AB - Gynaecology and obstetrics are medical fields where knowledge about the psychological and social factors influencing the patient's situation is essential. Some of these factors are risk factors for complications and illness during pregnancy and childbirth, and for reproductive health. Treatment and diagnosis of women with gynaecological disorders and of mother and child during pregnancy strongly influence mental health and well-being. Individual ways of coping with life events vary. In the individual approach to the treatment of women, gynaecologists need to have a broad understanding of the intrapsychic and social aspects of women's lives. This article lists some important fields of future research. We also discuss the necessity for systematic education in psychosocial gynaecology and obstetrics for clinical gynaecologists. PMID- 2919386 TI - [Nicotine chewing gums and lactation]. PMID- 2919387 TI - [Beta agonists, the background of the excitement?]. PMID- 2919388 TI - [Ectoparasiticides]. PMID- 2919389 TI - [Legal status in relation to services of veterinarians in the border area of another EEC member country, especially in relation to the administration of veterinary medications]. PMID- 2919390 TI - [To the welfare of man and animals]. AB - This inaugural address consists of three parts, starting with an elaboration of the fact that there is great differentiation among animals and humans. The second section goes into their interests. In the third section some practical relationships between humans and animals are discussed and some common denominators are sought. The title of the address is a well-known motto in the Dutch veterinary world: 'Hominum animaliumque saluti', which stands for: 'To the Welfare of Man and Animal'. PMID- 2919391 TI - [Amprolium residues in eggs following administration of amprolium/ethopabate in laying hens and breeding hens]. AB - Amprolium may be used as a coccidiostat in rearing hens and is a therapeutical agent used in laying hens. As a result of cross contamination, low amprolium levels may occur in feed. Feed containing a concentration of amprolium ranging from 5 to 250 mg/kg was therefore supplied to groups of laying hens. The amprolium residues in the yolks during and after treatment were subsequently determined. These levels varied from 1.75 mg/kg in the group fed 250 mg/kg to 0.2 mg/kg in the group fed 5 mg/kg. Amprolium levels in the whites of eggs were much lower than those in the yolks. The residues in yolks decreased below detectable levels (less than 0.005 mg/kg) within approximately ten days after treatment. Rearing hens in a tiered wire floor system were given amprolium in their feed until the first egg was laid. Amprolium residues in yolks were detected for well over a fortnight after the onset of laying. The amprolium residues determined in yolk did not exceed US tolerance levels of 8 mg/kg. PMID- 2919392 TI - [Eosinophilic granuloma of the oral cavity in a Siberian husky]. AB - An ulcerative sublingual inflammation was found to be present in a Siberian Husky dog. Histological examination revealed an eosinophilic granuloma. Treatment with corticosteroids was successful. PMID- 2919393 TI - [Campylobacter jejuni infections in The Netherlands]. PMID- 2919394 TI - Effect of 1,3-butanediol on rat liver microsomal NDMA demethylation and other monooxygenase activities. AB - The administration of 1,3-butanediol (BD) previously has been shown to elevate blood concentrations of ketone bodies, to potentiate carbon tetrachloride hepatotoxicity, and to increase the hepatic microsomal content of cytochrome P450 and the activity of aniline hydroxylase. In the present study, oral treatment (10 g/kg) with racemic BD and each of its enantiomers (R-BD and S-BD) induced NDMA demethylase activity by approx. 1.5-fold in rat hepatic microsomes obtained 12 h later, suggesting an induction of P450IIE1, the acetone/ethanol-inducible form of P450. The results agreed with an immunochemically determined increase in the levels of this isozyme. No change in P450 content, NADPH-cytochrome-c reductase, or in pentoxyresorufin dealkylase activity were detected. Blood levels of acetone were determined during a 10-h period after BD administration and showed a higher initial rate of increase by R-BD, possibly due to steroselective metabolic oxidative metabolism. However, no difference in the induction of NDMA demethylase activity by the enantiomers could be detected. Induction of P450IIE1 probably contributes to the previously described potentiation of haloalkane-induced hepatotoxicity by BD administration. PMID- 2919395 TI - Effects of dietary pyrrolizidine (Senecio) alkaloids on vitamin A metabolism in rats. AB - In two experiments, the effect of feeding the pyrrolizidine alkaloid (PA) containing plant tansy ragwort (Senecio jacobaea) on the metabolism of vitamin A in rats was examined. In Experiment 1, dietary levels of 0, 5 and 10% tansy ragwort and 0, 25,000 and 100,000 IU supplementary vitamin A/kg diet were used. In rats fed tansy ragwort, both plasma and liver concentrations of vitamin A were depressed (P less than 0.05). Plasma values were decreased to about 50% of control values. In Experiment 2, rats fed 5% tansy ragwort had depressed plasma and liver vitamin A concentrations 48 h after oral dosing with vitamin A. Fecal excretion of vitamin A was decreased in tansy ragwort-fed rats. In control rats, most fecal vitamin A was excreted in the first 24 h post-dosing, while in tansy ragwort-fed animals, the excretion was delayed, suggesting a possible effect of PA on gut motility. The results indicate that PA causes reductions in liver and plasma vitamin A concentrations. Postulated mechanisms include an effect of PA on hepatic retinol-binding protein synthesis, and impaired biliary excretion depressing vitamin A absorption. PMID- 2919396 TI - Arsenic-selenium interactions determined with cultured fish cells. AB - A fibroblastic cell line derived from gill tissue (designated BG/G) and an epithelioid cell line derived from fin tissue (designed BG/F) of bluegill sunfish (Lepomis macrochirus) were used as the bioindicators in toxicity experiments. The neutral red in vitro cytotoxicity assay served as the endpoint. In both cell lines the sequence of observed cytotoxicity was arsenite greater than arsenate greater than selenite greater than selenate, with each cell type exhibiting comparable ranking of midpoint toxicity (NR50) concentrations. Antagonistic interactions were noted between combinations of arsenics and seleniums. Thus, selenate and selenite (at nontoxic levels) reduced, but did not eliminate, the acute cytotoxicities of arsenate and, to a lesser extent, of arsenite. PMID- 2919397 TI - Renal clearance of aluminium: studies in the isolated perfused rat kidney. AB - The model of isolated rat kidney was used to study the renal handling of aluminium (Al). The kidney function remained unchanged at perfusate concentrations of Al in a range of 0.04-12.4 micrograms/ml during a perfusion period of 60 min. The clearance values of Al decreased with increasing concentrations of Al in the perfusate. The fractional Al clearance was reduced from 70% at the lowest Al concentration in the perfusate to 8.2% at the highest Al concentration. The Al content of the kidneys increased dose-dependently and reached a maximum value of 4 micrograms Al per kidney at a perfusate concentration of 5 micrograms Al/ml. Protein-binding studies with Al confirmed the suggestion that renal elimination of Al is dependent on the degree of Al binding. It is proposed that at low Al load in the plasma, the kidney possesses the capability to eliminate Al in an effective manner. PMID- 2919398 TI - Concentration-dependent depletion of non-protein sulfhydryl (NPSH) content in lung, heart and liver tissue of rats and mice after acute inhalation exposure to butadiene. AB - The effects of different exposure concentrations of butadiene on the cellular non protein sulfhydryl (NPSH) content of liver, lung and heart tissue were investigated in B6C3F1 mice and Sprague-Dawley rats. Groups of male animals of both species were exposed for 7 h to 10, 50, 100, 250, 500, 1000 and 2000 ppm butadiene. Immediately after exposure, NPSH content of liver, lung and heart tissue was determined according to a modified Ellman procedure. A comparison of both species shows that a dose-dependent NPSH depletion can be observed in mice for all tissues examined. In rats, liver NPSH content shows a major reduction at high exposure concentrations only. In mice, depletion of NPSH content of liver, lung and heart tissue starts at exposure concentrations of about 250 ppm butadiene. A reduction in NPSH content of about 80% is observed for lung tissue at 1000 ppm and for liver and heart tissue at exposure concentrations of 2000 ppm butadiene. The data on tissue concentrations of NPSH obtained after exposure of rats and mice to butadiene reflect the quantitative differences in butadiene metabolism and in biological effectivity of reactive butadiene intermediates between both species. PMID- 2919399 TI - Toxicological study of etoposide (VP-16) in rats with special emphasis on testicular alteration. AB - Etoposide (VP-16) was administered intravenously to rats for 3 months. Testicular alterations induced by etoposide (VP-16) at 0.5 and 1.5 mg/kg/d were thoroughly assessed with light and electron microscopy. Light microscopic analyses demonstrated disorganization and moderate depletion of germinal epithelium at 0.5 mg/kg/d, and complete germ cell depopulation at 1.5 mg/kg/d. Ultrastructural studies revealed degenerative changes in spermatogonia and early spermatocytes, appearance of large spermatids with multi-nuclei, and nuclear alterations and cytoplasmic vacuolation in Sertoli cells. Moreover, the basement membrane of the seminiferous tubule showed wavy lamellae and infolding to the seminiferous epithelium. Leydig cells manifested no significant ultrastructural changes. The small intestine and ovaries were not affected. The 2-month recovery period following cessation of treatment led to the recovery of these testicular alterations at the 0.5 mg/kg/d dose, but not at the 1.5 mg/kg/d dose. Judging from these results, etoposide (VP-16) induced damage primarily in spermatogenic cells, followed by Sertoli cells and the basement membrane in seminiferous tubules. Though reversible at intermediate doses, higher doses of VP-16 might produce irreversible testicular lesions. PMID- 2919400 TI - Effects of monosodium glutamate (MSG) on serum lipids, blood glucose and cholesterol in adult male mice. AB - Monosodium glutamate (MSG) was administered to adult male mice for 6 d at dose levels of 2, 4 and 8 mg/g b.w. Dose levels of 4 and 8 mg/g MSG resulted in significant changes in serum total lipids, triglycerides, phospholipids, free fatty acids and blood glucose 31 d after cessation of exposure. Administration of 2 mg/g MSG resulted in a decrease in blood glucose concentration but had no effect on the other measured end-points. No change in serum cholesterol was observed, either in free or esterified form or in different fractions of lipoproteins. PMID- 2919401 TI - The cyanide-metabolizing enzyme rhodanese in rat nasal respiratory and olfactory mucosa. AB - Hydrogen cyanide is a commonly occurring and highly toxic air pollutant. Inhalation of hydrogen cyanide would expose the nasal tissues to its toxic affects unless a detoxicating mechanism were available. Experiments with rat nasal tissues showed that the cyanide-metabolizing enzyme, rhodanese, is present in high concentrations, particularly in the olfactory region. The olfactory tissues had nearly 7-fold more rhodanese on a per mg mitochondrial protein basis than did the liver. These experiments show that nasal metabolism of cyanide may have an important influence on the toxicity of inhaled cyanide and cyanogenic materials. PMID- 2919402 TI - Cardiovascular, metabolic and neurologic effects of acute carbon monoxide poisoning in the rat. AB - Acute severe carbon monoxide poisoning was investigated in a modified Levine preparation. The rats inhaled 2700 p.p.m. CO for 90 min (COHb = 80%). Body temperature, heart rate and carotid systemic and 'stump' blood pressure declined sharply during CO exposure. By 2 and 4 h post-CO, body temperature and blood pressure had not renormalized, while heart rate was elevated. Blood glucose was unchanged at termination of CO exposure, but increased from 115 mg/dl to 191 mg/dl by 2 h post-CO. Hematocrit increased significantly during CO exposure, but no change in plasma volume was observed. Many rats showed one-sided muscle weakness and unidirectional rotation. By 4 h post-CO, behaviorally-assessed neurologic deficit was strongly correlated with an increase in left cerebral hemisphere water content, demonstrating a direct relationship between brain edema and dysfunction resulting from CO poisoning. PMID- 2919403 TI - Nafenopin, a peroxisome proliferator, depletes hepatic vitamin E content and elevates plasma oxidised glutathione levels in rats. AB - Male Sprague-Dawley rats were given oral doses of nafenopin (80 mg/kg/d) for up to 28 d. Nafenopin administration resulted in liver enlargement and induction of peroxisomal fatty acid beta-oxidation enzymes (which generate hydrogen peroxide), but little effect was observed on catalase and cytosolic GSH peroxidase was decreased. Hepatic vitamin E levels were depleted to around 50% of control. A small increase in hepatic oxidised glutathione (GSSG) content was paralleled in a time-dependent increase in plasma GSSG. These changes in vitamin E and GSSG levels may represent early indicators of oxidative stress produced in rat hepatocytes by nafenopin and other peroxisome proliferators as a consequence of the increased production of hydrogen peroxide. PMID- 2919404 TI - Increased alkylation of liver DNA and cell turnover in young versus old rats exposed to vinyl chloride correlates with cancer susceptibility. AB - To investigate the factors responsible for the high sensitivity of the livers of young rats to the carcinogenic stimulus of vinyl chloride (VC) adult and 11-day old Wistar rats were exposed to [1,2-14C] VC. Adult rats received either a single 6-h exposure, or 2 single 6-h exposures separated by a treatment-free time interval of 15 h. Eleven-day-old rats received 2 single 6-h exposures, according to the same treatment schedule. The animals were sacrificed 1 h after the end of the corresponding exposure period; liver DNA was isolated, enzymatically hydrolyzed and analyzed by column chromatography. Incorporation of [14C]VC derived radioactivity into the physiological deoxyribonucleosides (presumably reflecting the activity of DNA replication) was observed for all three sets of experiments. Virtually no difference in 14C-incorporation was observed between adult rats sacrificed immediately after one single 6-h exposure to [14C]VC and those which received a second exposure on the following day. In contrast, an about 8-fold increase in 14C-incorporation into the physiological purines of DNA of young versus adult rats was detected. This difference is indicative of a significantly elevated DNA synthesis/cell replication in the liver of young (11 d) rats. Radioactivity associated with 7-(2-oxoethyl)guanine was taken as an indicator of DNA alkylation by [14C]VC. Analysis of 7-(2-oxoethyl)guanine revealed that in adult animals the amount of this alkylation product formed is increased by a second exposure to VC. About 5-fold of the amount of 7-(2 oxoethyl)guanine present in adults could be determined in liver DNA of young (11 d) animals exposed under the same exposure conditions. Our results suggest that the high sensitivity of young rats to VC-induced hepatocarcinogenesis can reasonably be explained by enhanced DNA-alkylation and by increased cellular proliferation at an early age. PMID- 2919405 TI - Analysis of mutagenic activity in human urine after concentration on different resins and high-performance liquid chromatography. AB - Smokers' urine was tested for mutagenic activity on Salmonella typhimurium strain TA1538 with metabolic activation after adsorption on different resins and desorption with organic solvents. The amounts of XAD-2 were 1.25 and 5 g/100 ml urine, the amounts of alumina, cyanopropyl and C18 were all 5 g/100 ml and extrelut 80 g/100 ml. Adsorbed organic chemicals were eluted with acetone from XAD-2, with dichloromethane from extrelut and with a series of solvents from the other resins (hexane, toluene, dichloromethane and methanol). All columns gave similar results, with the exception of extrelut, which had poor recovery of mutagenic activity. Higher resin/urine ratios and sequences of columns gave better results. The organic eluates from XAD-2 columns loaded with the urine of patients treated with cyclophosphamide and melphalan were mutagenic on strain TA1535 with S9, and some mutagenic activity was also detectable in the aqueous eluate. Cisplatin was adsorbed on XAD-2, C18 and extrelut, but was eluted only from extrelut using dimethylformamide as a solvent. Smokers' urine was separated into several fractions with high-performance liquid chromatography, using C-18 columns with a series of solutions of 2.5 mM phosphoric acid and acetone or with a gradient of methanol. Several fractions containing dissolved organic compounds and no histidine were mutagenic with metabolic activation, but the overall mutagenic activity was still lower than the one detected with one-step chromatography on XAD-2. Using XAD-2 resins with a high ratio of resin to urine still seems to be the method of choice for studying urinary mutagenicity. PMID- 2919406 TI - Purification and properties of cytochrome P-450 from liver microsomes of phenobarbital-treated marmoset monkeys (Callithrix jacchus). AB - One form of cytochrome P-450 from phenobarbital-induced marmoset liver was purified to apparent electrophoretic homogeneity and compared with the major inducible form isolated from rat liver. Whereas spectral properties and molecular weights, as well as catalytic activities towards aminopyrine and ethylmorphine N demethylation are quite similar, rates of O-dealkylation with enzymes from the two species are considerably different. While ethoxycoumarin deethylation for the marmoset cytochrome is about one-fortieth of that for the rat, ethoxyresorufin and even pentoxyresorufin dealkylations for the marmoset form are not detectable. By contrast, aldrin epoxidation as catalyzed by this cytochrome is about three times as high as that obtained from the rat. PMID- 2919407 TI - Ortho-iodosobenzoic acid: its acute toxicity and neurobehavioral effects in mice. AB - o-Iodosobenzoic acid (IBA), in a surfactant micellar medium, is a rapid and efficient catalyst for the hydrolysis of organophosphate (OP) esters. Since little is known about the toxicity of IBA, a primary screen of neurobehavioral toxicity was evaluated in male ICR mice. IBA was administered intraperitoneally in a pH 7.4 phosphate buffer solution containing 8% dimethylformamide. The predominant overt signs of toxicity included an immediate and transient writhing reflex and/or persistent spasmodic myotwitching of the abdomen, and conspicuous suppression of orienting/exploratory behavior and emotional defecation. The dose ranges for ED50 of writhing response, suppression of rearing and spontaneous motor activity overlapped at levels of about one-tenth the acute LD50, 742 (633 856) mumol/kg, being 94.9 (74.5-122.5), 69.8 (47.9-105.4) and 71.1 (49.9-101.3) mumol/kg, respectively; the dose ranges for ED50 of abdominal myotwitching and depression of emotional defecation in a novel environment also overlapped but at levels of about one-fifth the acute LD50, being 138.4 (115.3-167.2) and 146.2 (110.7-196.3) mumol/kg, respectively. Morphine (1.25-10 mg/kg s.c.) antagonized the IBA-induced writhing response and abdominal myotwitching in a dose-dependent manner, with a PD50 of 4.2 and 4.9 mg/kg, respectively. The present report demonstrates that acute intraperitoneal administration of IBA produces an intriguing, non-specific behavioral syndrome, probably resulting from nociceptive stimulation. This implies that IBA might be irritating to the skin and mucosa. PMID- 2919408 TI - Influence of ochratoxin B on the ochratoxin A inhibition of phenylalanyl-tRNA formation in vitro and protein synthesis in hepatoma tissue culture cells. AB - Ochratoxin B (OTB), the dechloro-analogue of ochratoxin A (OTA), was studied separately and in combination with OTA on the aminoacylation of phenylalanine tRNA (tRNAPhe) catalysed by mice liver phenylalanyl-tRNA synthetase. OTB was neither a significant inhibitor of the reaction nor an antagonist of OTA. OTB was also assayed for its possible antagonistic effect on the in vivo protein synthesis inhibition caused by OTA in hepatoma tissue culture cells. No prevention of OTA inhibition could be found for OTB. It rather showed a slight additional inhibitory activity when mixed (100-180 microM) with low concentrations of OTA (40-60 microM). In conclusion, these results are not in favor of an antagonistic effect of OTB with respect to OTA action, at least on the level of cellular protein synthesis. PMID- 2919409 TI - Heparin anticoagulation. PMID- 2919410 TI - Estimation of error limits for cerebral blood flow values obtained from xenon-133 clearance curves. AB - I provide the theoretical basis for an error calculus for measurements of cerebral blood flow using a freely diffusible tracer substance such as xenon-133. The use of the error calculus is exemplified by a study of the effect on the error margins in measurements of gray matter blood flow from flow level, relative weight of the gray matter compartment, and use of the earliest parts of the clearance curves. The clinical value of the error calculus is illustrated by its ability to separate different sources of measurement error. As a consequence, it is possible to optimize the method for blood flow calculation from the clearance curves, depending on the type of cerebral blood flow measurement. I show that if a true picture of the regional gray matter blood flow distribution is sought, the earliest part of the clearance curves should be used. This does, however, increase the error in the estimate of the average cerebral blood flow value. PMID- 2919411 TI - Changes of blood flow in the cerebral cortex after subcortical ischemic infarction. AB - The two-dimensional xenon-133 inhalation method was used to measure cortical blood flow in 16 patients with small subcortical ischemic infarcts and in 10 patients with larger cortical infarcts in the chronic phase of stroke. An abnormal hemispheric asymmetry of blood flow was seen, not only in patients with cortical infarcts, but also in those with subcortical infarcts. In the patients with subcortical infarcts, focal areas of reduced cortical blood flow were seen in the symptomatic hemisphere remote from the tissue destruction, usually including part of the noninfarcted frontoparietal cortex. The cortical dysfunction may have contributed to the clinical manifestations including aphasia, which was present in 14 of the 16 patients with subcortical lesions. PMID- 2919412 TI - Mechanisms of vascular supersensitivity in hypercholesterolemia. AB - We have characterized in vitro, for the first time, the phenomenon of acute interaction between hypercholesterolemia and cerebrovascular function. We then used this model to investigate a number of mechanisms for the interaction. Rabbits fed a diet supplemented with 2% cholesterol developed hypercholesterolemia over 4 weeks with no histologically detectable atherosclerosis. This absence of anatomic change was reflected in normal biophysical elastic responses to graded radial stretch and normal optimum tension for responses to exogenous K+ in the selected arteries. However, basilar arteries removed from cholesterol-fed rabbits showed abolished myogenic responses to radial stretch and decreased median effective doses for added norepinephrine. These potentiated constrictor responses to norepinephrine were significantly correlated with increased plasma cholesterol concentration. A mechanism related to the opening of membrane calcium channels may be responsible for the supersensitivity. PMID- 2919413 TI - Atherosclerosis potentiates constrictor responses of cerebral and ocular blood vessels to thromboxane in monkeys. AB - The goal of our study was to examine the effects of infusion of serotonin and the thromboxane A2 analogue U46619 into one carotid artery to stimulate their release from platelets during aggregation. We measured blood flow to the brain and eye using microspheres and cerebral microvascular pressure in the pial arteries of normal and atherosclerotic cynomolgus monkeys. Unilateral intracarotid infusion of 10-30 micrograms/min serotonin did not affect cerebral blood flow in normal or atherosclerotic monkeys; serotonin did not alter blood flow to the eye in normal monkeys but decreased flow to the retina and choroid in atherosclerotic monkeys by 39 +/- 11% and 44 +/- 10% (mean +/- SEM), respectively. Infusion of 30 ng/min U46619 did not alter cerebral blood flow but increased the pressure gradient from the aorta to the pial artery, which is an index of large-artery resistance, in atherosclerotic monkeys. U46619 had no effect on blood flow to the eye in normal monkeys but decreased blood flow to the retina and choroid by 71 +/- 14% and 53 +/- 13%, respectively, in atherosclerotic monkeys. Thus, atherosclerosis potentiates the constrictor responses of large cerebral arteries to thromboxane and the responses of blood vessels of the eye to thromboxane and serotonin. PMID- 2919414 TI - A flavonoid inhibitor of 5-lipoxygenase inhibits leukotriene production following ischemia in gerbil brain. AB - Leukotrienes C4 and D4 are arachidonic acid metabolites that constrict blood vessels and enhance vascular permeability; their biosynthesis is initiated by the reaction of arachidonic acid with 5-lipoxygenase enzyme. After bilateral carotid artery occlusion for 15 minutes and reperfusion of the gerbil brain for 15 minutes, we determined the brain tissue concentrations of leukotrienes C4 and D4 by radioimmunoassay; they had increased from a baseline concentration of less than 1 to a mean +/- SEM concentration of 12.8 +/- 3.9 pmol/g brain. We also studied the effect of a flavonoid 5-lipoxygenase inhibitor on leukotriene production in the reperfused gerbil brain. A water-soluble flavonoid (5-hexyloxy 3',4'-dihydroxy-6,7-dimethoxyflavone 4'-disodium phosphate) was administered intravenously at a dose of 200 mg/kg body wt; 15 minutes later, both carotid arteries were occluded. The enhanced production of leukotrienes C4 and D4 in the reperfused brain was reduced by approximately 80% (from a mean +/- SEM of 12.8 +/ 3.9 to 2.2 +/- 1.3 pmol/g brain) in the presence of the 5-lipoxygenase inhibitor. The flavonoid did not affect the production of prostaglandin D2, the concentration of which also increased in the reperfused ischemic brain. PMID- 2919415 TI - Nicardipine reduces ischemic brain injury. Magnetic resonance imaging/spectroscopy study in cats. AB - We investigated whether the calcium channel entry blocker nicardipine would reduce ischemic brain damage in barbiturate-anesthetized cats subjected to permanent unilateral occlusion of the middle cerebral artery. The evolution of cerebral injury was assessed in vivo in 24 cats by a combination of proton magnetic resonance imaging and phosphorus-31 magnetic resonance spectroscopy for 5 hours following occlusion. Immediately thereafter, the volume of histochemically ischemic brain tissue was determined planimetrically in triphenyl tetrazolium chloride-stained serial coronal sections. Nicardipine was initially administered as an intravenous bolus injection of 10 mg/kg/hr 15 minutes before or 15 minutes after occlusion, followed by continuous infusion at 8 mg/kg/hr for the 5 hours of the experiment. Compared with untreated controls, cats that received nicardipine before or after occlusion showed a significant reduction in the extent of edema in the ipsilateral cerebral cortex, internal capsule, and basal ganglia. The results of phosphorus-31 magnetic resonance spectroscopy studies suggest that nicardipine may protect against cerebral ischemic damage by an action on cellular metabolic processes that preserve high-energy phosphates during the ischemic period. PMID- 2919416 TI - Effect of nimodipine on cerebral blood flow and metabolism in rats during hyperventilation. AB - Nimodipine shws promise in the prevention and treatment of brain ischemia. We examined the interaction of nimodipine pretreatment in a dose sufficient to prevent postischemic hypoperfusion and hyperventilation. We studied four groups of rats: normocarbia plus vehicle (Group 1, n = 5), hypocarbia plus vehicle (Group 2, n = 4), normocarbia plus nimodipine (Group 3, n = 7), and hypocarbia plus nimodipine (Group 4, n = 6). Groups 3 and 4 received 1 mg/kg i.p. nimodipine, and Groups 1 and 2 received an equivalent amount of vehicle. Ventilation was left unaltered in Groups 1 and 3 or increased to lower PaCO2 to 21-24 mm Hg in Groups 2 and 4. Determination of regional cerebral glucose utilization (rCGU) was carried out using the [3H]2-deoxyglucose method, and regional cerebral blood flow (rCBF) was determined by the indicator fractionation method using [14C]iodoantipyrine. The brain regions studied were the cerebral hemispheres, the diencephalon, the cerebellum, and the brainstem. Hyperventilation in Groups 2 and 4 from approximately 38 to 22 mm Hg reduced rCBF to 60% of normocarbic levels (p less than 0.05). The slope and intercept of this response were similar in vehicle- and nimodipine-pretreated rats. Nimodipine modestly decreased mean arterial blood pressure by 20% and increased plasma glucose concentration by 60% (p less than 0.05). Although nimodipine tended to increase rCBF and decrease regional cerebrovascular resistance (rCVR), this was significant only for hemispheric rCVR (p less than 0.05). There was a borderline effect for nimodipine to increase rCGU, especially during hypocarbia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2919417 TI - Role for gamma-aminobutyric acid in selective vulnerability in gerbils. AB - We tested the efficacy of various putative neuroprotective agents in the gerbil model of delayed neuronal death. The selective loss of anterior CA1 neurons of the hippocampus 4 days after 5 minutes of bilateral ischemia was complete in greater than 90% of the gerbils examined. We tested 11 agents for their ability to protect against neuronal loss. Only those agents that were associated with the GABAergic system exhibited protection and only when administered before the ischemic insult. The possibility that delayed neuronal death is the result of a primary defect in inhibitory neurotransmission is considered. PMID- 2919418 TI - Infarction of the medulla and cervical cord after fitness exercises. AB - The clinical association of a left lateral medullary syndrome with left corticospinal and posterior column deficits is reported in the case of a young woman with a left vertebral artery dissection. The signs are explicable on the basis of occlusion of branches of the vertebral artery to both the upper cervical cord and the medulla. The dissection may have been due to sustained rotation of the neck during fitness classes. In view of the undocumented benefits and the potential unwanted effects of this exercise, it is doubtful whether it should be recommended. PMID- 2919419 TI - Gadolinium-enhanced magnetic resonance imaging in multiple infarction. PMID- 2919420 TI - Clinical disagreement on the diagnosis of transient ischemic attack: is the patient or the doctor to blame? PMID- 2919421 TI - Human immunodeficiency virus seroprevalence among blood product recipients in San Francisco before transfusion. AB - To determine the incidence of transfusion-associated human immunodeficiency virus (HIV) infection after routine screening of donated blood, a pilot study estimated the pretransfusion prevalence of HIV infection among blood product recipients in San Francisco. Among the 911 nonduplicate pretransfusion specimens from recipients without a clinical history of acquired immune deficiency syndrome (AIDS) or AIDS-related complex (ARC), the overall prevalence of antibody to HIV was 2.9 percent (5.2% among males and 0.6% among females; p = 0.00002). If recipients in specifically defined or possible high-risk groups (n = 348) were excluded, a seropositivity rate of 1.8 percent (10/563) was detected, with all the positives occurring in men (10/242, 4.1%) and none in women (0/321, 0%). This demonstrated prevalence of HIV infection among blood product recipients in San Francisco before transfusion was substantially higher than the known 0.02 to 0.04 percent prevalence in the donor population. Therefore, the population of women without known risk for AIDS is the best in which to assess the risk of HIV infection in patients who are currently receiving seronegative blood transfusions. PMID- 2919422 TI - Complications of plasma exchange. AB - For the past few years, the Canadian Apheresis Study Group has collected data on most apheresis procedures carried out throughout the country. The information accumulated during calendar year 1985 has been reviewed, and the complications that occurred as a result of therapeutic plasma exchange (PE) have been assessed. There were side effects during 612 (12%) of the 5235 procedures done, involving 252 (40%) of the 627 patients treated. The most common reactions were fever, chills, urticaria, muscle cramps, or paresthesias; these reactions were encountered more frequently when plasma was used in the replacement fluid. Most reactions had little or no clinical significance. However, there were 28 severe complications, including one cardiac arrest and two respiratory arrests. Five late deaths occurred, but these were not related directly to PE. Although PE is relatively safe, life-threatening reactions do occur, and patients require careful observation during the procedure. PMID- 2919423 TI - Testing of maternal sera in pregnancies at risk for neonatal alloimmune thrombocytopenia. AB - The utility of prenatal testing of maternal serum for platelet-reactive antibody was assessed in 25 women at risk of delivering infants with neonatal alloimmune thrombocytopenia (NAT). Seventeen women were incompatible with their husbands for the PlA1 antigen and three for Baka; in five families, no demonstrable platelet specific antigen incompatibility was found. Analysis of the clinical outcome demonstrated that women with platelet-specific antibody detectable in any of the assays at any time during gestation were at risk of delivering thrombocytopenic infants (neonatal platelet count 31,250/microliters if mother did have antibody, as compared with 138,750/microliters if she did not; p less than 0.005). When only PlA1-incompatible pregnancies were examined, this association remained significant (mean neonatal platelet count in infants exposed to anti-PlA1, 34,285/microliters; that in infants not so exposed, 243,000/microliters; p less than 0.001). Changes in antibody strength throughout pregnancy did not correlate with the severity of NAT. The combination of the antigen-capture enzyme-linked immunosorbent assay and the indirect immunofluorescence test appeared to be most sensitive in detecting relevant platelet-specific alloantibodies. It is concluded that the detection of platelet-specific alloantibody in maternal serum in pregnancies at risk for NAT predicts moderate to severe NAT. However, the failure to detect such antibody does not always predict a normal neonatal platelet count. PMID- 2919424 TI - Blood and component wastage report. A quality assurance function of the hospital transfusion committee. AB - The transfusion service of a regional referral medical center issues a monthly blood and component wastage report to the Hospital Transfusion Committee. The report includes the amount and type of units wasted, who is responsible, and the cost incurred by the wastage. The individuals responsible for wastage include physicians, nurses, and laboratory personnel. Physicians are responsible for most wastage, principally by failing to administer thawed or pooled blood products. The Hospital Transfusion Committee initiated a wastage-reduction program that included a letter to physicians indicating the patient's name and the type of blood and/or components that the addressed physicians was responsible for wasting. Simple corrective actions results in a 73 percent reduction in our blood and component wastage. Monitoring of blood and component wastage should be routine quality assurance function of the Hospital Transfusion Committee. PMID- 2919425 TI - Heat inactivation of human immunodeficiency virus in solutions of antithrombin III. AB - Human immunodeficiency virus (HIV), isolated from cultures of infected peripheral blood lymphocytes, was added to solutions of highly purified antithrombin III (AT III), which was stabilized with 1 M citrate and 17 percent sucrose. The efficiency of heat inactivation of HIV in AT-III at 60 degrees C was compared with that of HIV in culture medium and followed for periods from 0 to at least 10 hours. The virus added, titer 10(5) by ID50, was inactivated as rapidly (less than 30 minutes) and efficiently (completely) in the stabilized AT-III as in the culture medium. Virus was determined both by direct measurement of the HIV related reverse transcriptase activity and by quantitation of virus infectivity by ID50 assay. PMID- 2919426 TI - Effect of diltiazem and a prostaglandin derivative (PGBx) on platelet function during long-term storage. AB - Calcium is an intermediate messenger between platelet stimuli and platelet response. Published studies have shown that the decreased ability of platelets to control calcium flux during long-term storage leads to platelet senility. Platelet metabolism might be more efficient during storage if pharmacologic agents that limit calcium movement were incorporated into the platelet concentrate storage solution. This hypothesis was tested by storing platelets with the calcium channel blocker, diltiazem, or with a prostaglandin B1 derivative, PGBx. During a 15-day storage period, platelets incubated with either diltiazem or PGBx showed improved function, as measured by aggregation, as compared to control platelets. The PGBx -enhanced platelet function during storage was accompanied by a significant decrease in glucose and an increase in adenosine triphospate concentrations. Platelet function after storage with PGBx improved in spite of significantly lower pH levels of the platelet concentrates at all time points tested. These studies suggest that the maintenance of calcium ion homeostasis during long-term platelet storage is important to in vitro platelet function even if the Ca2+ balance is maintained at the expense of pH and the glucose concentrations. PMID- 2919427 TI - Evaluation of a new, more oxygen-permeable, polyvinylchloride container. AB - A new container made of polyvinylchloride (PVC) with diethylhexyl phthalate (DEHP) used as the plasticizer was subjected to in vitro and in vivo evaluation for prolonged platelet storage. As compared with the original PVC bag, this bag has increased gas permeability by its reduced film thickness, larger surface area (400 ml capacity), and more porous label. The oxygen permeability coefficient, K(O2), of the new container was measured to be 655 nmol per min per atm. On the basis of previous studies relating the K(O2) to the maximal platelet count, it was predicted that this maximal count would be in the range of 7.9 to 8.9 X 10(10) platelets. This prediction was confirmed by carrying out 58 studies measuring pH, pO2, and platelet count on platelet concentrates (PCs) stored for up to 7 days. After 5 days of storage all PCs with counts above 8.0 x 10(10) had pH less than or equal to 7.0, whereas those with counts below 8.0 x 10(10) had pH greater than or equal to 7.0. Six units (10%) with counts above 9.0 X 10(10) had pH levels of 6.5 or below. Thirteen of the PCs underwent extensive in vitro testing of platelet function during 7 days of storage. No significant differences were found in pH, ATP content, and decrease in platelet count, as compared with studies (n = 22) using PCs stored in polyolefin containers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2919428 TI - Preparation of packed red cells suitable for intravascular transfusion in utero. AB - Intra-cardiac transfusion in utero is a recent development in the treatment of erythroblastosis foetalis. As with intra-umbilical cord transfusion, the procedure has been described as having a high risk of complication characterized by bradycardia and cardiac-arrest. Intra-coronary hyperkalemia was suspected as being a major contributing factor towards the complications experienced, particularly by the intra-cardiac delivery. The procedure is warranted, however, in cases where intra-umbilical cord transfusion is not possible. Therefore, studies comparing various methods of preparing packed cells for intravascular transfusion were initiated. The plasma potassium levels of gravity sedimented packed cells and saline washed red cells resuspended in either Ringer's lactate, pooled donor plasma or saline were measured. Products of saline washed/resuspended packed red cells transfused within 2 hours of preparation were found to have low potassium levels while exposing the fetus to minimal risk of transfusion transmitted infection and were therefore selected to be the most suitable product. Using this product, a significant decrease in the incidence of severe bradycardia resulting in cardiac-arrest, following intravascular transfusion (32 procedures) was observed. PMID- 2919429 TI - Transfusion medicine: law, ethics, and profession. PMID- 2919431 TI - The algorithm and the crossmatch. PMID- 2919430 TI - Quality control and evaluation of leukocyte-depleting filters. PMID- 2919432 TI - Of oil changes and their complications. PMID- 2919433 TI - The sensitivity and specificity of the immediate-spin crossmatch. AB - The immediate-spin (IS) crossmatch is used to detect ABO incompatibility between donor red cells (RBCs) and the serum of the intended recipient. However, this test may be positive in the absence of ABO incompatibility (false positive) or it may be negative when ABO incompatibility exists (false negative). During a 25 month study, the rates of both false-positive and false-negative IS crossmatch results were evaluated, and the sensitivity and specificity of the IS crossmatch were determined. During the study period, 53,656 IS crossmatches were performed for patients without significant RBC antibodies. Fifty-five patients had positive IS crossmatches, and no false-negative reactions were found. In tests of 55 patients with positive IS crossmatches, 77 false-positive and 5 true-positive reactions were noted. The causes of the false-positive reactions were rouleaux (36 patients), cold-reactive antibodies (8 patients), a combination of rouleaux and cold-reactive antibodies (2 patients), fibrin clot (1 patient), and undetermined (3 patients). The sensitivity and specificity of the IS crossmatch were 100 and 99.86 percent, respectively. Laboratory personnel should be aware that the IS crossmatch may have false-positive or false-negative results, and they should develop written protocols to distinguish quickly between true positive and false-positive reactions. PMID- 2919434 TI - American Society of Transplant Physicians. 1988 presidential address. PMID- 2919435 TI - Effects of calcium channel blockers on in vivo cellular immunity in mice. AB - In vitro studies have shown that calcium channel blockers (CCB) inhibit lectin induced lymphocyte proliferation. However, no in vivo effects have been documented yet. In this study we evaluated the effects of CCB on in vivo cellular immunity by using contact sensitivity to oxazolone in mice. From 15 to 30 twelve week-old female C3H mice were randomized into: 0.9 NS (sham), ethanol, CsA, dexamethasone (DXM), verapamil, diltiazem, and nifedipine groups. These study agents were given daily from day 1 to day 9 subcutaneously to the shaved abdominal wall. The mice were sensitized with oxazolone to the abdominal wall on day 2 and challenged with oxazolone on the right ear on day 8. Delayed-type hypersensitivity was measured on day 10 and defined as the difference in thickness between the right (challenged) and left (control) ear of each mouse. The mean DTH of each study group was compared with that of the sham, and the statistical significance was determined by a Student's t test. The percentage of change in DTH from the sham was also calculated as: (mean DTH of study drug group mean DTH of sham group)/mean DTH of sham group x 100%. A negative value meant a suppressive effect on DTH; a positive value, an enhancing one. The CsA, DXM, and nifedipine all had significant suppressive effects on DTH. Verapamil had a significant enhancing effect. Ethanol and diltiazem had no significant effect. More studies employing other antigens with several other cell-mediated response measurements along with DTH quantification should be done in order to determine the specificity of the immunosuppressive effect of CCB as well as the potential of any calcium antagonist as an adjuvant suppressive agent. PMID- 2919436 TI - The effect of dimethyl sulfoxide on the absorption of cyclosporine in rats. PMID- 2919437 TI - Subpopulations of human lung alveolar macrophages: ultrastructural features. AB - Lung alveolar macrophages (LAM), obtained by bronchoalveolar lavage of healthy donors, were separated into four subfractions on discontinuous gradients of Percoll and subjected to light microscopic, transmission (TEM) and scanning electron microscopic (SEM) studies. Alveolar macrophage morphometric analysis was performed on cytocentrifuged preparations. TEM of subpopulations revealed considerable morphologic heterogeneity. By SEM, cells of the most dense (D) subfraction were small, round, and, typically, the surface was highly ruffled with small membrane pseudopods. Cells of the least dense subfraction (A) showed a low degree of membrane folding or filopodia and were often totally disorganized. In smokers, macrophages of fraction A had a greater area and perimeter compared with non-smokers, whereas the inverse relationship was observed for C and D cells. Also, the number of electron-dense inclusions and the level of acid phosphatase were higher in smokers than in non-smokers. Coupled with functional heterogeneity the morphologic differences described in this paper suggest that density-separated subpopulations of LAM may represent different stages of differentiation or maturation. PMID- 2919438 TI - Ependymoma of the foramen of Monro: ultrastructural characterization. AB - The characteristics of clear cells of an ependymoma of the foramen of Monro have been studied by electron microscopy to precisely define its organellar composition and to establish the tumor histogenesis. Our data confirm that the once-thought oligodendroglial is, in fact, an ependymal tumor. Both the scarce number of organelles, owing to the low degree of differentiation, and the abundance of hyaloplasmic lipid vacuoles can account for the clear appearance of these tumor cells. PMID- 2919439 TI - Malignant oncocytic carcinoid of the pancreas. AB - We report a rare case of malignant oncocytic carcinoid of the pancreas including the diagnostic immunocytochemical and electron microscopic findings. In addition the tumor shows some unusual ultrastructural features: lamelliform cristae and cytoplasmic and nuclear crystalline structures. PMID- 2919440 TI - Cellular junctions in nonepithelial tumors (UP12:389-405, 1988) PMID- 2919441 TI - [Prevention and conservative treatment of involuntary and difficult urination]. PMID- 2919442 TI - [Soft intraocular lenses]. AB - Hard intraocular polymethylmethacrylate (PMMA)-lenses have been implanted following cataract extractions since 1949, and their good properties are well proven. Soft intraocular lenses have only been implanted since 1976. Their chemical and physical properties, advantages and disadvantages are discussed with reference to the well known PMMA-lenses. In the short term the patients obtain the same visual acuity with soft intraocular lenses as with hard intraocular lenses, and it is the impression, that the soft lenses are more tissue compatible, but more prolonged follow up is required. PMID- 2919443 TI - [Training of patients with urinary incontinence]. AB - The different types of urinary incontinence are defined and the possible educational treatment modalities are described. Stress incontinence may be treated by pelvic floor exercise and bio-feed-back. The object is training in muscle awareness with the purpose of teaching the patients to squeeze without activating the abdominal muscles. Significant improvement can be obtained in 22 63% of the patients. Urge incontinence can be treated by bladder drill and bio feed-back. Voluntary control over the detrusor reflex is re-educated and the patients are instructed to adhere to a fixed voiding schedule every three hours. In women, 80% may be improved. In reflex incontinence, prophylactic bladder emptying may be initiated by stimulation of specific trigger points. Overflow incontinence may be reduced by optimal voiding technique and clean intermittent self-catheterization. Postmicturition dribble can be relieved by manual emptying of the urethra. No treatment is known for giggle incontinence. In nocturnal enuresis, conditioning treatment is recommended. Immediate waking is essential. Environmental incontinence is treated by securing easy access to voiding facilities and by training in toileting skills. Half of the patients are curable. PMID- 2919444 TI - [Training of patients with residual urine and/or recurrent urinary tract infections]. AB - The principles for voiding instructions to patients with symptoms due to residual urine and to patients with recurrent urinary tract infection are reviewed and motivated. Residual urine may be reduced by triple voiding at one-minute intervals, fixed voiding intervals of three hours and by treatment of constipation. Additional abdominal straining and manual suprapubic expression may be necessary. To improve the voiding technique, pelvic floor training or bio-feed back are advocated with the purpose of teaching the patients to strain without squeezing the pelvic floor muscles. In cases without symptomatic relief, clean intermittent self-catheterization is advocated. The frequency of recurrent, uncomplicated, symptomatic, bacterial urinary tract infections may be halved by copious fluid intake (at least 2 litres per day), voiding every three hours in the daytime regardless of desire to void, triple voiding until the bladder is empty and regular bowel emptying. Women are advised to void after sexual intercourse. PMID- 2919445 TI - [Organic disease among patients at an open psychiatric outpatient clinic]. AB - All of the new consultations in the Copenhagen Municipal psychiatric outpatient department during a period of three month were registered. Out of these, 1,149 did not lead to admission of the patient. In 47% of these information about somatic condition was available and in 31% information about somatic disease was present. Were 21% of the 1,149 patients were concerned, there were indications for treatment of the somatic disease. 50% of these were treated by the medical staff of the department, 17% were treated in other psychiatric departments, 21% were treated in departments for somatic disease and 11% were referred to their general practitioners or practising specialists for further treatment. These findings emphasize the importance of medical referral in an open psychiatric clinic with direct therapeutic contact. PMID- 2919446 TI - [Measurement of alcohol in saliva with a test strip]. AB - As the concentration of alcohol in saliva follows the concentration of alcohol in the blood meticulously, a test strip to measure alcohol in saliva would provide an easy and rapid method of semiquantitative estimation of the blood alcohol concentration. The authors have submitted Alco-Screen test strips to trial by comparing five different batches by measurement on aqueous solutions of alcohol, saliva to which alcohol had been added and also in practice. The batch variations were very great and the results obtained on aqueous solutions and saliva with added alcohol were too high whereas the results in practical use were, in general, too low. In addition, it was found that the colour of the reagent field was difficult to compare with the reference fields. Instructions for use were incomplete and easily misunderstood. PMID- 2919447 TI - [Psychiatric admissions among city bus drivers. A prospective study]. AB - During the period from 1978 until and including 1984, 2,645 male bus drivers were followed as regards psychiatric admissions. In 1978, 83% of these had replied to a questionnaire about job-satisfaction and working conditions. Fifty-eight out of these 2,465 had been admitted to psychiatric departments during the follow-up period, corresponding to 117 admissions. The commonest diagnoses on discharge were affect reactions with a total of 35 discharges. The number of admissions to psychiatric hospitals among bus drivers was compared with the number of admissions among Danish men in 1981. Significantly fewer admissions among bus drivers were found in the diagnostic group manic depressive psychoses, reactive conditions and for all psychiatric admissions. On the other hand, the number of admissions among bus drivers where the diagnoses of affect reactions, paranoid conditions and non-specific psychoses were found to be significantly higher (standard morbidity ratio statistic = 217) than for Danish men. Odds-ratio for psychiatric admissions among the 2,045 bus drivers who had replied to the questionnaire in 1978 were significantly raised for the bus drivers who did not feel their work monotonous, were divorced, felt unbalanced and frequently stressed. Previous smokers had significantly lower odds ratio as compared with others. PMID- 2919448 TI - [Accidental explosions in Denmark when working on containers for combustible fluids]. AB - Gases may be formed in containers for inflammable fluids and these may burn explosively if lit. Even apparently empty containers may contain sufficient quantities of gas to result in violent explosions precipitated by procedures which produce heat or sparks in the neighbourhood of the container. Seventeen persons were found to be injured in accidents of this type in a Danish investigation. Two of the accidental injuries proved fatal. The serious risk involved in handling and treating containers which contain or have contained inflammable fluids is, therefore, emphasized. PMID- 2919449 TI - [Admissions of persons aged 17-49 years to non-psychiatric departments]. AB - Based upon data from the Danish National Patient Register, the number of somatic admissions during the period 1977-1984 was summed up in two municipalities with an average annual population of 30,426 persons in the age group 17-49 years. 38% of the male population and 48% of the female population in this age group had been admitted at least once during the period (excl. pregnancy conditions). 1% of the population had more than nine admissions which was 18% of all admissions. 4.5% had more than four admissions which was 38% of all admissions. No difference was observed as regards sex, and age was of minor importance for the frequency of admissions. A significant statistical association was found between the number of admissions and abuse, suicidal attempts, and psychiatric illness. About half of the patients (males 56%, females 43%) with more than nine admissions were discharged with one of the "non-organic" diagnoses on at least one occasion. Patients with "non-organic" diseases had an average of 5.2 admissions during the period compared with the other diagnoses with an average of 2.7 which was 20% of all admissions. There were more males with abuse diagnoses and a majority of 30 49 year-olds among the cases of psychiatric illnesses. Apart from this, no significant differences as regards sex and age were found among these diagnostic groups. PMID- 2919450 TI - [Bowenoid papulosis in men. Sexually transferred intra-epithelial neoplasia of the ano-genital region]. AB - The clinical picture in three cases of Bowenoid papulosis is reported. Histology indicates carcinoma in situ changes and koilocytosis. Evidence points to the role of human Papillomavirus in the etiology of the disease. PMID- 2919451 TI - [Acute pancreatitis with few symptoms complicated by segmentary colitis]. AB - A case of acute pancreatitis with few symptoms complicated by spontaneously remitting segmentary colitis is described. The possibility of overlooking the colonic complications in acute pancreatitis is emphasized. The pathogenesis and therapeutic possibilities are mentioned. PMID- 2919453 TI - [Cancer treatment]. PMID- 2919452 TI - [Perinatal mortality and infant mortality during the period 1979-1985. Causes of death in perinatal deaths during the period 1985-1986]. PMID- 2919454 TI - [Bone metastasis]. AB - Bone metastases are frequently one of the first signs of disseminated disease in cancer patients. In the majority of patients, the primary tumour originates from the breast, prostate or lungs. Even although the prognosis is serious, a proportion of the patients will survive for several years and will thus require active treatment. More than 25% of the patients have no symptoms whereas pain dominates in the remainder. Frequent complications are pathological fractures, hypercalcaemia and spinal cord compression. Normally, the diagnosis can be established from the clinical picture compared with a series of laboratory analyses, x-ray investigations of the skeleton and bone scintigraphy. As treatment is mainly palliative, the purpose is primarily relief of pain, prevention of fractures and ensuring a reasonable functional level. The therapeutic possibilities comprise local treatment in the form of surgery and irradiation and also systemic treatment in the form of chemotherapy, endocrine therapy and possibly diphosphonates. of these, irradiation still plays the most important role. About 80% of the patients respond to treatment and, after 12 months, 50-70% of the surviving patients will still be free from pain. Only few randomized investigations are found in the literature available and the criteria of response are, in general, difficult to interpret. There is, therefore, a great requirement for more clinically controlled investigations which assess the efficacy of the numerous therapeutic possibilities. PMID- 2919455 TI - [Meconium ileus equivalent]. AB - Meconium ileus equivalent (MIE) can be defined as a clinical manifestation in cystic fibrosis (CF) patients caused by acute intestinal obstruction by putty like faecal material in the cecum or terminal ileum. A broader definition includes a more chronic condition in CF patients with abdominal pain and a coecal mass which may eventually pass spontaneously. The condition occurs only in CF patients with exocrine pancreatic insufficiency (EPI). It has not been seen in other CF patients nor in non-CF patients with EPI. The frequency of these symptoms has been reported as 2.4%-25%. Pathophysiologically, MIE is probably caused by a combination of EPI, increased intestinal transit time, and abnormal intestinal mucus. The treatment should primarily be non-operative. Specific treatment with N-acetylcysteine, administrated orally and/or as an enema is recommended. Enemas with the water soluble contrast medium, meglucamine diatrizoate (Gastrografin), provide an alternative form for treatment and can also serve diagnostic purposes. It is important that the physician is familiar with this disease entity and the appropriate treatment with the above mentioned drugs. Non-operative treatment is often effective, and dangerous complications following surgery can thus be avoided. PMID- 2919456 TI - [Serious infections in alcoholics. 1. Bacteremia, lobar pneumococcal pneumonia and pneumococcal meningitis in alcoholics 1974-1987]. AB - During the period 1974-1987, the frequency of infections in alcoholics discharged from hospitals in Funen showed an increase of 5.53 +/- 3.38 (p = 0.0039) per 10,000 alcoholics discharged per year. The frequency of discharged alcoholics increased by 3.72 +/- 0.60 per 10,000 discharged patients per year. Infections were diagnosed in 0.48 per cent of the discharged alcoholics and in 0.18 per cent of the discharged non-alcoholics (p less than 0.00001). Pneumococcal infections were relatively more frequent in alcoholics (p less than 0.05). PMID- 2919457 TI - [Serious infections in alcoholics. 2. Etiology of bacteremia and meningitis in alcoholics discharged from hospitals in Funen 1981, 1984 and 1986]. AB - In 1981, 1984 and 1986 relatively more episodes of bacteremia with Corynebacterium in one or two tubes out of twelve were found in alcoholics and these normally negligible episodes may be a iatrogenic marker of intubation and esophagoscopy in alcoholics. Definite bacteremic episodes with E. coli, Staphylococcus aureus, Klebsiella, Streptococcus pneumoniae, Proteus, Pseudomonas aeruginosa, Enterobacter, Streptococcus faecalis, haemolytic Streptococcus and Bacteroides were found in 0.79% of alcoholics and 0.37% of non-alcoholics (0.01 greater than p greater than 0.001). The frequency per 100,000 discharged patients with positive blood cultures irrespective of bacteriological diagnosis, and also alcoholic liver cirrhosis was 8.12 = about two thirds of the number of deaths from cirrhosis per year. In selected cases of severe infections in alcoholics, the frequency of cirrhosis or steatosis was 29/48 = 60%. Foci were more often demonstrated bacteriologically in patients without cirrhosis or steatosis (0.01 greater than p greater than 0.001). Bacteremia with Staphylococcus aureus was a complication of treatment 6-18 days from admission, whereas bacteremia with E. coli and Pneumococci was present on admission. Serious bacteremia in alcoholics was not found in patients over 70 years of age and the many geriatric alcoholics (4.7%) did not show a greater morbidity than the average geriatric patient. The mortality of bacteremic alcoholics was more than 45% over a 6-year period. PMID- 2919459 TI - [Births, abortions and extrauterine pregnancies in the community of Funen during 1974-1986]. AB - A retrospective investigation was undertaken of all the births and abortions during the period 1974-1986 in the County of Funen. The material comprised 66,020 births, 23,179 induced abortions, 9,270 spontaneous abortions and 1,344 ectopic pregnancies. The distributions of the various types of pregnancy were assessed for the entire period and correlated with the age of the women. Comparison of the circumstances in 1974 and 1986 revealed significant changes (p less than 0.05) for pregnant women greater than or equal to 35 years with the following values: the number of births increased 20%, the number of spontaneous abortions increased 56%, the number of ectopic pregnancies increased 240% and the number of induced abortions fell 31%. These numerical values are probably representative for all Denmark. PMID- 2919458 TI - [Surgical treatment of otosclerosis. Effects and risks]. AB - Surgical treatment of otosclerosis involves an opening of the labyrinth and, accordingly, a risk of complications from that organ: vertigo and sensorineural hearing loss or anacusis. During the past decade, the number of new patients with otosclerosis has stabilized at a low level in Danish ENT-departments. Thus, typically the number of stapedectomies per year per department is between 10 and 25. The study elucidates effects and risks at the operation, focusing in particular on the question whether this treatment ought to be centralized. In a seven-year period, a total of 75 stapedectomies in 73 patients with otosclerosis were performed at the ENT-department, Glostrup Hospital, Copenhagen. No revision operations were included. Hearing gain was obtained in all patients except two and the conductive hearing loss was eliminated in 87% of the cases. One patient developed severe sensorineural hearing loss caused by granuloma around the prosthesis, a very rare complication of uncertain cause. Thus, the results were satisfactory but in this series all operations except two were performed by the same expert surgeon in a department with high activity in otosurgery for other diseases. If similar conditions are not available a certain degree of centralization should be considered. The long-term results and the question of bilateral stapedectomy are discussed. PMID- 2919460 TI - [Functional levels in nursing homes residents assessed by the Gottfries-Brane Steen scale]. AB - Thirty-three inhabitants in a nursing home were evaluated by the Gottfries-Brane Steen scale. The evaluation showed that more than one third of the residents had marked dementia, especially with intellectual symptoms. The residents showed a high degree of motoric problems. It is concluded that dementia is a common cause for placement in a nursing home, although it seldom is recorded in detail as such before admission. PMID- 2919461 TI - [Placing of patients with dementia in nursing homes as evaluated by the Gottfries Brane-Steen scale]. AB - Sixteen gerontopsychiatric inpatients were compared with 33 residents in a somatic nursing home by Gottfries-Brane-Steen scale. Both groups showed symptoms of mental deterioration of intellectual and also emotional character. The gerontopsychiatric inpatients showed significantly more emotional deterioration than the others. It was concluded, that especially the emotional defect in combination with intellectual deterioration is the cause of the placement in a psychiatric ward. PMID- 2919462 TI - [Changes in the standardized resolutions and procedures for regional scientific ethical committees in Denmark]. PMID- 2919463 TI - [Smoke poisoning. Inhalation injuries from remaining at the scene of a fire]. AB - In 1987, 87 persons died in Denmark as the result of fires. Fifteen of these occurred after arson. The commonest immediate cause of death in connection with fire is smoke inhalation. The pathophysiology of smoke inhalation is reviewed. The injurious effects on health may be subdivided into three different groups, viz thermal injuries to the respiratory passages, hypoxia and carbon monoxide poisoning and the toxic effects on the pulmonary parenchyma of various compounds (particles, gases and steam) which develop from the burning materials in the process of burning. After this, the symptomatology and treatment of smoke inhalation are reviewed. Treatment is primarily supportive and symptomatic. Finally, the various fire-extinguishing agents employed to extinguish fires at present are reviewed. Some of these have potentially injurious effects. PMID- 2919464 TI - [Supracondylar fracture of the femur following total knee replacement]. AB - A total of 157 cases of well-documented supracondylar fractures of the femur in patients with knee replacement on the ipsilateral side are reviewed. Predisposing factors and methods of treatment are described and a possible therapeutic model is presented. PMID- 2919465 TI - [Regional differences in the use of cholecystectomy in Denmark during the period 1977-1985]. AB - In a register-based study of all cholecystectomized patients in Denmark during the period from 1977-85 (37,048 patients) an account is given of the regional variations observed in connection with the intervention. The cholecystectomy operation is sub-divided into four types of operation dependent on whether the intervention is merely a matter of cholecystectomy or it involves the choledocus, the duodenum, the small intestine or other organs. The variation analysis is based on a division of the country into 75 areas, each primarily served by a single hospital. The method highly reflects the differences in clinical treatment strategies. The summarized rate of cholecystectomy for this period of time was 8.2 per 10,000 persons. In areas with the highest and the lowest rates of operation the figures were 12.3 per 10,000 and 5.1 per 10,000, respectively. In 18 areas, the rates of operation were significantly higher than average and in 18 other areas significantly higher than average and in 18 other areas significantly below average. SCV-score (X100) 2.19. There is no systematic correlation between the degree of specialisation in the operating department and the frequency in employing the operation. Areas with an operation index significantly above average had the same rate of more complicated operations than simple cholecystectomy as the other areas. Possible causes of national as well as international variations in the use of cholecystectomy are discussed, and the need for a radical evaluation of this kind of treatment is emphasized. PMID- 2919466 TI - [Emergency medical services during the Nijmegen march in 1987. A consecutive prospective study]. AB - In connection with the international Nijmegen march, EDB controlled registration of the first-aid services provided by the Danish first-aid team was carried out. The object of this was to register the pattern of injuries among the participants and correlate this with their health backgrounds in order to assess the possibility of selecting potential risk groups among the participants. Out of 487 uniformed Danish participants (442 men and 45 women) 249 (51.1%) consulted the first-aid team. In addition, 70 other persons also consulted the first-aid team. These consisted mainly of foreigners in uniform and Danish civilian participants. The 319 participants received a total of 862 EDB registered services: 140 (44%) consulted the first-aid team on one occasion while the remaining 179 (56%) had from two to 16 consultations (mean three). The median age was significantly higher for those who had one consultation only as compared with the remainder (24 as compared with 22 years). Just under 2/3 of the participants who received first aid services were smokers and significantly more smokers were found among those who participated for the first time. Uniformed persons from the womens' services who participated differed from their male colleagues by having significantly fewer skin complaints. A total of nine out of the 487 participants dropped out (1.8%) but only eight of these had been in contact with the first-aid services. These figures are too limited to permit selection of actual risk groups. PMID- 2919467 TI - [Breech presentation deliveries]. AB - A total of 5,519 consecutive single deliveries at term were analysed for maternal and foetal factors associated with breech presentation (UK). The protocol in this department for breech deliveries which permits vaginal delivery of foetuses estimated to be between 2,400 and 3,800 g in cases where the pelvis was considered to be clinically normal, was also evaluated. Breech presentation was found in 173 cases. In 102 of these circumstances were present which permitted trial of vaginal delivery. Seventy-seven were delivered vaginally. An increased frequency of low Apgar scores (less than 8) after one minute was demonstrated among infants delivered vaginally in the breech presentation on comparison with infants delivered by Caesarean section, whereas low scoring after five minutes occurred with the same frequency. One infant died during delivery. Follow-up of infants delivered in breech presentation (mean period of observation two years) showed developmental disturbances in three of the vaginally delivered infants and in five of those delivered abdominally. Two of the infants delivered abdominally had severe cerebral paresis and psychomotor retardation without evidence of intrauterine or severe neonatal asphyxia. On comparison with the population delivered in cephalic presentation (HST), significantly increased frequencies of primiparity and light-for-dates infants were found in the breech presentations. Low Apgar score after one minute was significantly more frequent in breech presentations while low Apgar scoring after five minutes occurred with the same frequency. The perinatal mortality rates in breech and cephalic presentations were 17.3 and 4.7 per 1,000 respectively. Following correction for lethal malformations, the rates were 5.8 and 3.8 per 1,000, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2919468 TI - [Cardiotocographic monitoring of deliveries. A prospective comparative study of 2 types of electrodes]. AB - The number of electrodes employed, the frequency of reapplication, the technical quality of monitoring and the complications of use of spiral electrodes and Copeland electrodes for cardiotocographic monitoring of deliveries are assessed in a prospective randomized investigation. The number of electrodes employed and the frequency of reapplications were significantly lower employing Copeland electrodes. Similarly, the electrode signal was significantly better as assessed by the percentage of the duration of monitoring in which the cardiotocogram did not register during the second stage of labour on account of poor electrode signals. No differences were found in the frequencies of complications or subjective discomfort in the mother on employing the two types of electrodes. PMID- 2919469 TI - [Serious complications of sternal puncture]. AB - Fatal complications of sternal puncture are, as a rule, the result of penetration of the needle through the sternum followed by lesion of the pericardium and myocardium and finally pericardial tamponade and death. Thirty-four such cases are studied with a view to the technique and especially the site on the sternum where the puncture was made. It was supposed that the punctures in the sternum in the fatal cases were performed below the level of the second intercostal space and that that was the primary cause of the fatal outcome as the heart and pericardium here are very close to the sternum. Punctures at the level of the second intercostal space and higher should be reasonably safe. To the astonishment of the author, it was found that many of the fatal punctures were made in the sternum at the level of the second intercostal space or higher. The many reports in the literature were examined again and it was concluded that the complications might be due to inexperience and lack of training of the person who performed the puncture. It is concluded that puncture of the iliac crest with marrow aspiration and biopsy is preferable for better diagnostic value and a safer procedure. PMID- 2919470 TI - [Prognosis after surgery of infrarenal abdominal aortic aneurysm]. AB - During the period from January 1972 to September 1984, 285 patients were admitted and treated operatively for abdominal aortic aneurysm (AAA). At operation a non ruptured AAA was found in 177 patients and a ruptured AAA in 108 patients. Advanced age and reduced renal function were found by employment of Cox's regression analysis to influence the peroperative and postoperative mortalities. The commonest cause of postoperative death was renal failure both in cases of non ruptured and ruptured AAA. The commonest causes of late deaths were coronary occlusion, malignant disease, cerebral haemorrhage and haemorrhage from the anastomosis. PMID- 2919471 TI - [AIDS without recognized HIV status. 2 cases of AIDS without prior recognition of HIV status]. AB - Two cases of fatal Pneumocystis carinii pneumonia in middle aged homosexual men, not previously suspected of HIV-infection are presented. Neither had consciously considered himself at risk of contracting AIDS which emphasizes the need for differentiated information campaigns as well as vigilance on the part of the medical profession outside specialized centers. PMID- 2919472 TI - [Infantile arterial calcification]. AB - A case of idiopathic infantile arterial calcification combined with hydrops foetalis is presented. The pathogenesis, symptomatology and diagnosis are reviewed. PMID- 2919473 TI - [Cerebral infarction in systemic lupus erythematosus]. AB - The case-history of a man aged 31 years with systemic lupus erythematosus and cerebral infarction is presented. Although patients with active disease are young, cerebral infarcts are strikingly frequent among them. PMID- 2919474 TI - [The Ethics Committee's position on the criteria of death]. PMID- 2919475 TI - Intraprostatic tumor location and pelvic lymph node metastatic pattern in early prostate cancer. AB - Recently we treated 54 patients with clinically localized prostate cancer: 8 had Stage A disease, 13 had Stage B1, 32 Stage B2, and 1 Stage C. Fifty of these patients underwent bilateral pelvic lymphadenectomy and retropubic radical prostatectomy, while the other 4 patients underwent bilateral pelvic lymphadenectomy only. Pathologic staging revealed pelvic lymph node metastases in 12 patients. We reviewed these 12 Stage D1 cases to see whether or not the intraprostatic tumor location influenced the locoregional metastatic nodal pattern. We found that metastases occurred ipsilaterally in 5 cases, while the other 7 patients experienced bilateral pelvic involvement. We failed to find any case in which contralateral nodal involvement occurred without the tumor also involving the pelvic lymph nodes ipsilateral to the intraprostatic tumor. The data suggest that it would be reasonable to perform pelvic lymphadenectomy only on the same side of the prostatic lesion. This modified approach potentially could reduce morbidity and cost to the patient. PMID- 2919476 TI - Management of extraperitoneal ruptures of bladder caused by external trauma. AB - We reviewed 105 cases of extraperitoneal bladder rupture admitted to our hospitals from 1959 to 1985. Primary suturing of the rupture was performed in 65 patients, and catheter drainage alone without suturing of the rupture was performed in 34. The incidence of blunt trauma causing the rupture of gross hematuria on admission, and of associated injuries was similar in both groups. There was a higher incidence of women older than sixty years in the group managed by catheter drainage alone, and a higher incidence of laparotomy for associated intra-abdominal injuries and a higher mortality rate in the group treated by primary suturing. There were three early complications in the group treated by suturing (hematuria with clot retention 2, sepsis contributing to death 1) and four early complications in the conservatively treated group (hematuria with clot retention 1, pseudodiverticulum with bone spike in its floor 1, persistent urinary fistula 1, and sepsis contributing to death 1). There were two late complications in 42 patients followed in the group treated by suturing (urethral stricture 1, frequency and dysuria 1), and three late complications in 14 patients followed in the conservatively treated group (hyperreflexic bladder 2, urethral stricture and vesical calculi 1). Catheter drainage alone for extraperitoneal rupture from external trauma was simple, quick to perform, and appealing in the multiple-injured patient. Although the early and late complication rates were higher in the conservatively managed group, there was no statistically significant difference from the group treated by primary suturing. PMID- 2919477 TI - Radiation therapy-associated invasive bladder tumors. AB - Radiotherapy-associated bladder carcinoma was found in 3.7 percent of 244 cases of advanced urothelial carcinoma. Average age at diagnosis of the bladder tumor was 63.1 years, with a mean of 20.5 years between radiation treatment and diagnosis. All 9 patients presented with gross hematuria. Eight patients had transitional cell carcinoma, 7/8 (87.5%) also had vascular or lymphatic invasion, and 1 was adenocarcinoma. Mean survival was 15.4 months (range 1-40 mos.), with a 55.5 percent one-year disease-free survival after diagnosis. Four patients died of bladder tumor, 4 were alive with no evidence of disease, and 1 was alive with metastasis. PMID- 2919478 TI - Progressive systemic sclerosis (scleroderma) and impotence. AB - Scleroderma, a connective tissue disorder involving multiple organ systems, can be a causal factor in erectile dysfunction. Cases are presented where arteriographic and biopsy evidence supports this. Awareness of this association could make possible an early diagnosis and influence treatment choices. Corpus cavernosum biopsy has been utilized to this end. PMID- 2919479 TI - Integrated cystoscope: first rigid multipurpose operating cystoscope for local anesthetic endoscopy. AB - The Miller Integrated Cystoscope is the first small-diameter (17 Ch), rigid, multipurpose, operating cystoscope (biopsy, urethrotomy, ureteric catheterization, cutting, retrieval of stones and foreign bodies, and injection) designed with patient comfort in mind. Despite a small outside diameter, the 8.7 Ch instrument channel conducts a 7.5-Ch accessory including the unique rigid Endoknife, which converts it into an optical urethrotome and rigid Endoneedle which can deliver local anesthetic and other pharmacologic agents into the bladder, prostate, and urethra of both male and female patients. The simplicity of design has dispensed with the need for more costly and conventional instrumentation (e.g., optical urethrotome, Albarron lever) at a fraction of the cost. The urologist can not only inspect the lower urinary tract (Cf fiberscopes) but also perform endoscopic procedures short of a full transurethral prostatectomy with maximum patient comfort. PMID- 2919480 TI - Percutaneous removal of "extra-renal" residual urinary calculus. AB - We report a case of an "extra-renal" calculus and associated perinephric abscess treated by endourologic techniques. The calculus could have fallen into the perinephric tissues at the time of open renal surgery. PMID- 2919481 TI - Posterior urethral valves. Role of temporary and permanent urinary diversion. AB - Between 1960 and 1983, 67 boys were treated for posterior urethral valves. Despite adequate valve ablation, azotemia eventually developed in 19, and they underwent permanent urinary diversion. Normal renal function was not achieved in any of these children. Diversion does not appear to have changed the natural course of their renal insufficiency, which is most likely secondary to damage incurred prior to their initial presentation. Prognostic factors useful to identify this select population are examined. PMID- 2919482 TI - Diphallia associated with malformation of hindgut derivatives. AB - A case of diphallia associated with bifid scrotum and duplication of urethra, bladder, and large intestine is reported. PMID- 2919483 TI - Ureteral calculi in children: review of 50 consecutive cases. AB - Fifty children presenting with ureteral calculi over a twenty-year period were studied retrospectively. There were 35 boys and 15 girls, with a mean age of five and a half years. Nineteen patients had a urinary tract anomaly: 11 had an obstructed megaureter, and 8 had previously undergone urinary tract surgery. Forty-four children had infection stones and the remaining 6 oxalate calculi. Infected urine was found in 35; the infecting organism was a Proteus species in 23. Metabolic abnormalities were detected in 2 children. Operative removal of the stones was done in 39 patients, and in the remaining 11 patients the stones passed spontaneously. There were 6 recurrences, all within four years of initial presentation. PMID- 2919484 TI - Double pigtail (D-P) stent catheter with tether in Kock pouch ileal reservoir. PMID- 2919485 TI - Modulation of hematoporphyrin derivative-sensitized phototherapy with corynebacterium parvum in murine transitional cell carcinoma. AB - The interaction of photodynamic therapy (PDT) with hematoporphyrin derivative (Hpd) and immunotherapy with Corynebacterium parvum (CP) was studied in a murine transitional cell carcinoma (MBT-2) model. C3H/He mice were transplanted subcutaneously in the hind limb with 2.5 X 10(5) tumor cells. One day after transplantation, mice were randomized into groups to receive saline (control), PDT, CP 25 micrograms, CP 250 micrograms, CP 25 micrograms + PDT, and CP 250 micrograms + PDT. PDT was administered by intraperitoneal (IP) injection of Hpd (12.5 micrograms/g body weight), followed twenty-four hours later by photoirradiation. CP was given intralesionally at the same time as IP injection of Hpd (24 hours before photoirradiation). A low dose of CP (25 micrograms) was shown to enhance the effect of PDT while PDT reduced the benefit obtained with high dose of CP (250 micrograms). In a second series of experiments, CP (250 micrograms) treatment after photoirradiation was shown to give significantly greater benefit than CP treatment before photoirradiation. The study thus indicates that the effectiveness of combined immunophototherapy is dependent on the sequence of the combination and its intricate relationship with the dosage of CP. The enhancement of PDT by low dose of CP in this model suggests the usefulness of this combined immunophototherapy in enhancing tumor control and in lessening deleterious side effects. PMID- 2919486 TI - Leiomyoma of spermatic cord with unusual features. AB - We describe a case of a patient with osseous metaplasia and chronic inflammatory changes in a leiomyoma of the spermatic cord, as well as a lipoma of the cord with similar changes. The differential diagnosis and possible etiology of these findings are presented. PMID- 2919487 TI - Hyperinsulinism associated with primary renal cell carcinoma. AB - A case is reported of a patient with symptomatic hyperinsulinism associated initially with a renal cell carcinoma and then later, with secondary deposits from the same tumor. Evidence points to a strong possibility of renal tumor involvement in the production of insulin hypersecretion. PMID- 2919488 TI - Renal hydatidosis. AB - Renal hydatidosis in humans is rare, although it is not uncommon in sheep- and cattle-raising countries. We describe a patient who had renal hydatidosis with hydatidcysturia. PMID- 2919489 TI - Remarkable effect of endocrine therapy on brain metastasis from prostatic carcinoma. AB - The brain metastasis of prostatic carcinoma is rare and is distinguished by its poor prognosis in cases which are not surgically resectable. Herein we report on a case of brain metastasis of prostatic carcinoma which showed a dramatic regression through bilateral orchiectomy and doses of diethylstilbestrol diphosphate and estramustine phosphate. Neurologic and psychiatric symptoms diminished within three months, and the patient is alive and well without any subjective symptoms after twelve months. PMID- 2919490 TI - Benign hepatic masses mimicking metastatic renal cell carcinoma. AB - Making the distinction between a benign hepatic mass and renal cell carcinoma metastatic to the liver is crucial in evaluating a patient with renal cell carcinoma. The erroneous diagnosis of metastatic renal cell carcinoma may deter the surgeon from performing a potentially curative nephrectomy. In this report, we present 1 patient with cavernous hemangiomas and another patient with focal nodular hyperplasia of the liver. In each case the benign liver lesion was incorrectly diagnosed initially as metastatic renal cell carcinoma. The radiographic appearance of these lesions is discussed in detail. PMID- 2919491 TI - Role of linear tomography in evaluation of patients with nephrolithiasis. AB - One hundred twenty-four consecutive patients with suspected or known nephrolithiasis were referred for evaluation by linear tomography. Renal calculi were detected in 98 patients (79%). Linear tomography revealed more renal calculi than did preliminary KUB films in 46 patients (37%), although in only 10 cases (8%) was the tomogram positive if the KUB was negative. Exact quantification of the numbers and locations of renal stones is important in patients to be managed metabolically, and in those being evaluated in advance of or following percutaneous or extracorporeal lithotripsy. PMID- 2919492 TI - Nondilated obstructive uropathy. PMID- 2919493 TI - Retrograde balloon dilation of urethra. PMID- 2919494 TI - Neoplasia involving the middle ear cavity of dogs. AB - Eleven cases of neoplasia which involved the middle ear cavity of dogs are recorded. Eight of the tumours originated in the external ear canal and comprised four adnexal tumours, one squamous papilloma and three adenocarcinomas of the ceruminous glands. Papillary adenomas were recognised within the middle ear cavity of two dogs. In one animal the precise origin of an anaplastic carcinoma involving the middle ear could not be determined. Only five of the tumours were amendable to surgical excision and four dogs survived for more than eight months after surgery. PMID- 2919495 TI - An evaluation in pigs of Nobi-Vac AR and an experimental atrophic rhinitis vaccine containing P multocida DNT-toxoid and B bronchiseptica. AB - The trial involved eight large white sows obtained from a closed experimental specific pathogen free herd. Four sows (two each for an experimental vaccine and for Nobi-Vac AR) were vaccinated twice (eight weeks and two weeks before parturition) with 2 ml of vaccine administered intramuscularly. Two unvaccinated sows were used as an infected control group and two unvaccinated sows served as an uninfected control group. Forty-six piglets (28 from vaccinated sows and 18 from unvaccinated sows) were challenged by intranasal instillation of Bordetella bronchiseptica at two days of age and Pasteurella multocida type D, dermonecrotic toxin at seven days of age. Among the infected control group some piglets died and there were clinical signs of pneumonia and severe turbinate atrophy. In the vaccinated groups the results showed that immunisation of the pregnant sows had provided a good level of antibodies, which were transmitted to their offspring. There was a significant reduction in the clinical signs and no lesions were observed in the group vaccinated with the experimental vaccine and only moderate atrophy of the turbinates in the Nobi-Vac AR group. B bronchiseptica and P multocida were never recovered from the lungs of the vaccinated groups and in the nasal cavities their frequency declined with age. PMID- 2919496 TI - Relationship between wing flapping at shackling and red wingtips in chicken carcases. PMID- 2919498 TI - A new insurance form. PMID- 2919497 TI - Bovine and human infestation with Parasitus consanguineus Oudemans and Voigts (Mesostigmata:Parasitinae). PMID- 2919499 TI - Antibiotic resistance. PMID- 2919500 TI - [Methodological approaches to studying the influence of parental occupation on the development of malignant neoplasms in children]. PMID- 2919501 TI - [Follicular hyperplasia of the regional lymph nodes in stomach cancer and its prognostic significance]. AB - Degree of follicular hyperplasia of regional lymph nodes (LFH) in patients with gastric tumors (T1-4N0M0) was evaluated versus 5-year survival, age, tumor size, depth of invasion and histologic pattern. Stage II-III LFH was found to have a favorable prognosis. Tumor size proved a factor influencing the degree. No apparent relationship between age, depth of invasion and degree of tumor cell differentiation, on the one hand, and LFH stage, on the other, was established. PMID- 2919502 TI - [The rate of tumor growth and cell loss in cervical cancer]. AB - Time of tumor volume doubling, mitotic index and share of pathologic mitoses were identified in 61 patients with squamous-cell cervical tumors and the importance of cell loss evaluated. Tumor doubling time ranged 58-1500 days (average 314 +/- 37); mitotic index--0.1-3.7% (average 1.07 +/- 0.07%); percentage of pathologic mitoses 1-89% (average 28.9 +/- 1.6%); cell loss--92.0-99.9% (average 98.2 +/- 0.2%). Cell loss was found to be significantly different in groups of patients characterized by different rates of tumor growth and was directly proportional to tumor doubling time. There were no significant differences in mitotic index or pathologic mitosis share in groups with different rates of tumor growth. It is suggested that cell loss is determined by the tumor-bearer's antitumor systems to a considerable degree. PMID- 2919504 TI - [Effect of ionol on carcinogenesis in the kidneys]. AB - The effect of treatment with an antioxidant--ionol (2,6-di-tert-butyl, 4 methylphenol)--on nitrosodimethylamine-induced carcinogenesis was studied. Large doses of ionol were found to inhibit tumor development in the kidney. This also involved intensification of spontaneous peroxidation of renal cortical membrane cell lipids which in turn was inhibited when additional stimulation with iron was carried out. PMID- 2919503 TI - [The action of inhibitors of the amine nitrosation reaction in human gastric juice and in the body of animals]. AB - The effect of ascorbic, ferulic and caffeic acids on dimethylamine and amidopyrine nitrosation in a medium containing 3 samples of total gastric juice taken from 10 humans (pH = 6.1; 3.2 and 1.7) was studied versus the amount of inhibitor added to the medium. The resultant relationship proved bizarre, the inhibitor at low concentrations stimulating nitrosation in some situations. When gastric juice concentration in the medium was further lowered by dilution with a buffer at relevant value of pH, the paradoxical effect of inhibition gradually disappeared. PMID- 2919505 TI - [Effect of estradiol dipropionate on the development of uterine sarcoma induced by 1,2-dimethylhydrazine in mice]. AB - The study was concerned with the influence of single dose of estradiol dipropionate on its promoting effect on 1,2-dimethylhydrazine-induced tumors in female CBA/CaLac mice. Estradiol dipropionate given within 19 weeks did not affect carcinogenesis whereas 39-week treatment stimulated uterine sarcoma development irrespective of single dose and schedule of administration. PMID- 2919506 TI - [The complex diagnosis of nonorganic neoplasms of the small pelvis]. AB - The paper discusses the results of examination of 205 cases of extra-organ tumors of the small pelvis carried out in 1967-1986. The study group included 65 pediatric and 140 adult patients, 57 (28%) males and 148 (72%) females, 194 primary and 11 relapsing cases. Patients aged under 4 years (47, i. e. 23%) prevailed. Benign tumors were detected in 83 (40.5%) and malignant ones--in 122 (59.5%) cases. Disease was asymptomatic in 39 (19.0%) patients and presented with multiple symptoms in 166 (81.0%). Rectally, the upper pole of lesion was palpable in 47 (22.9%) while the lower one--in all cases. Tumors which took up as much as two-thirds of the small pelvis cavity were found in 37 (56.9%) pediatric and 31 (22.1%) adult patients. Tumorous or secondary lesions of adjacent organs were detected rectoscopically in 47 of 74 (63.5%) cases: sensitivity (s)-88.6%, specificity (sp)-57.1%; using chromocystoscopy--in 43 of 64 (67.2%): s-89.5%, sp 75.0%; pelvic pneumography-31 of 56 (55.3%): s-68.8%, sp-54.5%; excretory urography-53 of 79 (67.0%): s-88.3%, sp-68.4%; irrigoscopy-55 of 79 (69.6%): s 82.4%, sp-75.0%; angiography-30 of 70 (42.8%): s-90.9%, sp-78.4% and computer tomography--in 42 of 45 (93.3%) patients: s-96.4%, sp-88.2%. Four stages of diagnosis were suggested. PMID- 2919507 TI - [Side effects in chemoradiotherapy of bladder cancer]. AB - Chemoradiation treatment was given to 60 patients with locally-advanced cancers of the urinary bladder and their recurrences. Split-course radiotherapy was carried out using a rotation technique at 3-4 week intervals. Total focal dose for two courses was 65-70 Gy. Combined therapy used cyclophosphamide, dactinomycin and cisplatin. Chemotherapy was given immediately after each course of irradiation. Concomitant cardiovascular pathology was registered in 46.6% of patients and renal function derangement--in 36.6%. However, all the patients, except three, received treatment matched by symptomatic therapy. Myelosuppression was among major side effects. Response was assessed in 47 cases (75%). The immediate effect of combined treatment was observed in 57.4%. PMID- 2919508 TI - [The aldosterone level as a probable prognostic factor in patients with kidney cancer]. PMID- 2919509 TI - A population-based study of children with standard risk acute lymphoblastic leukemia in the five Nordic countries. A follow-up of 230 patients. AB - Two hundred and thirty children with standard risk acute lymphoblastic leukemia (ALL) were diagnosed during a period of 3 years from July 1, 1981 to June 30, 1984 in the five Nordic countries. Criteria for standard risk ALL were age above 2.0 and below 10 years, WBC less than or equal to 20 x 10(9)/l, no evidence of CNS-involvement, mediastinal mass or T- or B-cell leukemia. The children were treated without prophylactic CNS irradiation, the majority (200 patients) according to two treatment programs. Follow-up of the entire group after a minimum of 30 months showed 64% of the children living in complete continuous remission with a probability of event-free survival of 0.60. The treatment results are not entirely satisfactory and intensification of therapy is required. A subgroup of patients with WBC between 10 and 20 x 10(9)/l and with adverse prognosis was identified, justifying a change of the present criteria for risk grouping. PMID- 2919510 TI - Hypoxia reinforces laryngeal reflex bradycardia in infants. AB - The laryngeal chemoreflex involves bradycardia, apnea, swallowing and peripheral vasoconstriction. This reflex was studied in twelve infants, aged 5 days-28 weeks, who had sustained an apparent life-threatening event or were siblings of infants who had died of the sudden infant death syndrome. The bradycardic and apneic components of the reflex were found to be significantly, and sometimes powerfully, reinforced when elicited by pharyngeal water instillation during acute, mild hypoxia (transcutaneous PO2 4.6-8.3 kPa). Apnea duration during normoxia was 0.7-15 sec, and during hypoxia 2-30 sec. Heart rate change ranged from +26% to -21% during normoxia, as compared with -4% to -63% during hypoxia. The percentage change in heart rate was found to inversely correlate with the transcutaneous PO2-level prevailing when the reflex was elicited. The conclusion is that there is a significant reinforcement of the cardiorespiratory adjustments when the laryngeal reflex is activated during simultaneous excitation of the peripheral arterial chemoreceptors. One infant, showing a particularly strong increase of the cardiorespiratory response to laryngeal receptor stimulation during hypoxia, later died of sudden infant death syndrome. PMID- 2919511 TI - Dental caries in Turkish immigrant primary schoolchildren. AB - Dental caries and the utilization of the Public Dental Service in Sweden were investigated in 84 Turkish immigrant children born in Sweden, 69 Turkish children born in Turkey and 85 Swedish age- and sex-matched controls. Dental fear was also studied. The mean age of the children was 8.3 years. Turkish immigrant children had more caries both in the primary and in the permanent teeth than Swedish children. Children born in Turkey had more caries in the primary dentition than those born in Sweden. Turkish children came more often for emergency visits than Swedish children and expressed dental fear more frequently. Turkish immigrant children therefore constitute a high risk group for caries and need supervision early after immigration. PMID- 2919512 TI - Influence of malnutrition on cognitive development assessed by Piagetian tasks. AB - Cognitive development of 1336 children (6-8 yr) was studied in relation to their nutritional status. Seven Piagetian tasks covering the mental process of a concrete operational period were given to each child to assess the cognitive development. Weschler intelligence scale for Indian Children was used to assess the IQ of each child. The percentage of malnourished children in stage I of development (preoperational) was significantly higher as that of wellnourished children. A higher percentage of children in the latter group was in stage III of development (concrete operation). In boys performance on all the tasks was influenced by undernutrition except for class inclusion. In girls this was true only for conservation of liquid, substance and ordinal relation. The results of the regression analysis showed that nutrition was the only factor weakly associated with the poor performance of the children in various tasks. Further, the effect of nutrition was more pronounced in conservation tasks indicating poor verbal reasoning and comprehension in malnourished children. Information was also collected regarding the parental education and occupation, socio-economic status, caste, economic sufficiency, psychosocial stimulation and home environment. However, these environmental factors did not influence the development of rural children. This might be due to the fact that the population in the present study did not vary much with regard to these variables. PMID- 2919513 TI - Lower incidence of elevated umbilical cord serum IgE concentration in infants of hepatitis B carrier mothers. PMID- 2919514 TI - Hallucinations and hyperthermia after promethazine ingestion. PMID- 2919515 TI - Furosemide and ethacrynic acid: risk factors for the occurrence of serum electrolyte abnormalities and metabolic alkalosis in newborns and infants. PMID- 2919516 TI - Pituitary enlargement, hypertrichosis and blunted growth hormone secretion in primary hypothyroidism. AB - Pituitary hyperplasia, hypertrichosis and blunted growth hormone (GH) secretion were observed in three children with untreated primary hypothyroidism. These abnormalities disappeared and improved after thyroid hormone therapy. The recognition of these associations may eliminate unnecessary surgery and GH therapy and lead to the choice of thyroid hormone replacement therapy. PMID- 2919517 TI - Cardiac involvement in postnatal rubella. AB - Two cases of rubella myocarditis are reported: a 6-year-old boy who developed a complete, distal to His, atrioventricular block, during the third day of illness; and a 12-year-old boy who developed myocarditis with congestive heart failure 20 days following rubella infection. Although permanent pacing was required in the first patient, six years later he showed a normal growth and maintained normal activity. The second patient has deteriorated markedly and 6 months after the initial illness he had severe heart failure. It should be noted that myocarditis with abnormalities of the conduction system or congestive heart failure may be a complication to postnatal rubella. PMID- 2919518 TI - Reversible pulmonary arterial hypertension in a 6-year-old girl with extrinsic allergic alveolitis. AB - A case is reported of a 6-year-old girl who developed extrinsic allergic alveolitis due to hypersensitivity to her pet budgerigars. Pulmonary artery pressure measurements obtained by a cardiac catheterization demonstrated a significant increase in the pulmonary vascular resistance during the acute stage of the disease. Six months after exclusion of exposure to the budgerigars the hemodynamic of the pulmonary circulation was normalized. The present case thus shows that a reversible increase in the pulmonary vascular resistance in extrinsic allergic alveolitis of childhood may occur without development of an irreversible pulmonary fibrosis. PMID- 2919519 TI - Coexisting hereditary methaemoglobinaemia and heterozygous beta-thalassaemia. AB - Cyanosis was noted within a few weeks after birth in two sisters. On investigation the cause of cyanosis was found to be congenital methaemoglobinaemia due to NADH diaphorase deficiency. Heterozygous beta thalassaemia was present as an additional incidental finding in one of the sisters, but did not contribute to the symptoms, thus showing that the two diseases, when coexistent, do not pose additional haematological problems. However, it is possible that the beta-thalassaemia counteracts the tendency to compensatory erythrocytosis induced by methaemoglobinaemia. PMID- 2919520 TI - First description of "Indian childhood cirrhosis" in a non-Indian infant in Europe. AB - The first female child of healthy German parents, breast-fed for 5 weeks, developed progressive abdominal distension due to hepatosplenomegaly at the age of 7 months and died from acute liver failure 3 months later. Histology showed destruction of liver architecture with extreme hepatocellular copper storage, characteristic of "Indian childhood cirrhosis" (ICC). The family received drinking water from a well via copper pipes. The copper level of the water was extremely elevated (430 and 5510 micrograms/l) so that exogenous copper intake during the first months of life may have induced the fatal liver disease, probably in association with an unproven genetic disposition. This is the first description of a case of ICC in a member of a non-Indian family in Europe. PMID- 2919521 TI - The duration for which exclusive breast-feeding is adequate. A study in Jordan. AB - The object of this study was to determine the length of time for which exclusive breast-feeding supported adequate growth in a cohort of infants from families in and around Amman, Jordan. The infants were described as "faltering" if their incremental growth over 4 weeks fell below -2 standard deviations of the increments reported by Fomon in the USA. The infants were examined every 2 weeks until they faltered, or, without faltering, were started on supplementary foods. In general, up to the time of faltering, growth was satisfactory by international standards. The median time of faltering was 6 months. The results support the view that, at least in this relatively well-nourished community, exclusive breast feeding is satisfactory for 4-6 months. However, further examination is needed of the risk factors that lead to early faltering in some breast-fed children. PMID- 2919522 TI - Protein C activity and antigen in premature and fullterm newborn infants. AB - Blood was obtained from 23 premature infants (birthweights 950-2910 g at 26-35 gestational weeks), and 27 fullterm infants (birthweights 2930-4900 g at 37-42 gestational weeks). Protein C concentration and activity were analysed. In preterm infants, protein C concentrations were 2.9-24% of adult values, and those of protein C activity 6-32%, the corresponding figures for term infants being 16 60% and 8.5-60%. Protein C concentrations were below 10% of adult values in four low birthweight infants, three of whom had significant haemorrhages. Protein C activity was below 10% of adult values in three infants, all of whom suffered from major haemorrhages. PMID- 2919523 TI - The outcome of neonatal septicemia during fifteen years. AB - The outcome of neonatal septicemia in 320 infants seen during 1969-83 has been evaluated. Mortality decreased from 27% to 12%. The incidence of moderate to severe handicaps in survivors remained unchanged at around 20%. Sixty percent of these handicapped children had meningitis or osteomyelitis, and many of these were healthy prior to onset. All handicapped infants without osteomyelitis or meningitis had several other risk factors that may have contributed to the final outcome. PMID- 2919524 TI - Flavobacterium meningosepticum infections in a neonatal intensive care unit. AB - An outbreak of nosocomial infections by Flavobacterium meningosepticum in a neonatal intensive care unit is described. During a period of eleven weeks two patients presented with septicaemia and meningitis. In addition, nine patients were found to be colonized and three of these neonates developed septicaemia. The infected patients were treated with clindamycin and piperacillin. All the patients survived, but the neonates with meningitis developed hydrocephalus. An extensive bacteriological screening of the staff was negative, but in the ward environment, F. meningosepticum was found around sinks, on rubber stoppers for milk bottles and on "cleaned" teats. Several infection control measures were instituted. Established routines were revised, with particular emphasis on the handling of objects containing or in regular contact with water. PMID- 2919525 TI - Staphylococcus aureus bacteraemia in children below the age of one year. A review of 407 cases. AB - The bacteriology, epidemiology, infection types and mortality were reviewed in 407 cases of Staphylococcus aureus bacteraemia in the period 1967-1984 in children less than one year old. The number of bacteraemia cases in this age group increased in the seventies, but only 4% of the bacteraemias seemed to be due to epidemic spreading. Neonates might be at higher risk for S. aureus bacteraemia than older children less than one year old, and nearly all infections in the neonatal period were hospital-acquired. The mortality was 24%, and did not correlate with type of infection, but in neonates it correlated with low birthweight. PMID- 2919526 TI - Aetiology of congenital hypothyroidism in Finland. AB - In Finland a nationwide screening programme for congenital hypothyroidism (CHT) has operated since 1980 with complete coverage. Among the total of 307,000 newborns screened, the incidence per 100,000 was 24.6 for thyroid dysgenesis and 4.0 for dyshormonogenesis. We conclude that, when screening is based on cord serum TSH, the false-positive results are caused mainly by difficult delivery. The most important factors associated with dyshormonogenesis were CHT in the family, origin from a geographic risk area, and origin of both mother and father from the same community. These reflect the autosomal recessive inheritance. The risk factors for dysgenesis were female gender, CHT in the family, birth in a geographic risk area, and birth during a risk period of the year. PMID- 2919527 TI - Serum antibodies to cow's milk proteins in pediatric inflammatory bowel disease: Crohn's disease vs. ulcerative colitis. AB - Serum antibodies to five cow's milk proteins, alpha-casein, bovine serum albumin (BSA), beta-lactoglobulin A and B (BLG-a, BLG-b) and alpha-lactalbumin (ALA) were investigated in young patients with inflammatory bowel disease, 56 with Crohn's disease (CD), 24 with ulcerative colitis (UC). IgG antibodies against BSA and BLG a and -b were higher in Crohn's disease patients as compared to those with ulcerative colitis and controls. The IgG anti-BSA were higher in the group of CD patients with higher score of disease activity. Additionally, IgA antibodies to alpha-casein were higher in CD and UC compared to control. These findings may be due to increased uptake of dietary antigens or enhanced immunological response occurring in CD patients. PMID- 2919528 TI - Dysfunction of the monocyte-macrophage system in the idiopathic minimal change nephrotic syndrome. AB - We studied the function of phagocytes and the distribution of lymphocyte subpopulations in 23 patients with Idiopathic Minimal Change Nephrotic Syndrome. All the patients were in relapse at the time of the study. The latter was performed before specific therapy was started. Our control group consisted of 26 normal children who were studied while undergoing routine analysis prior to plastic surgery. Polymorphonuclear leukocytes from the patients showed no alterations in their ability to ingest and to kill candidas. On the contrary, peripheral blood monocytes had a normal phagocytic function with a decreased candidacidal activity when compared to normal controls (p less than 0.001). No correlation was found between serum immunoglobulin levels and the monocyte lytic function. The absolute number of B lymphocytes was significantly increased (p less than 0.05), whereas the absolute number of total lymphocytes, T lymphocytes and T4+ and T8+ cell subsets did not differ from those of the age-matched normal controls. Natural killer cells were functionally normal. PMID- 2919529 TI - The prevalence of bacteriuria among high risk neonates in Nigeria. AB - Among the 446 high risk neonates studied for significant bacteriuria and pyuria in the neonatal wards of the Obafemi Awolowo University teaching hospital Complex, Ile-Ife, 7.6% and 5.8% were positive for significant bacteriuria and pyuria respectively, while none of the 81 infants in the control group were positive. Males and females were similarly affected and there was no seasonal variation in the prevalence of pyuria or bacteriuria. It is noteworthy that 25 (96%) of the 26 pyuria neonates also had bacteriuria emphazising the significance of pyuria as a possible screening method for urinary tract infections in neonates. The clinical problems in the neonates studied included prematurity, low birthweight, neonatal jaundice, fever, CNS symptoms, ophthalmia neonatorum, prolonged rupture of the membranes (PROM), respiratory distress, septic cord/skin, diarrhoea, vomiting and feeding problems. Only prematurity and low birthweight were significantly associated with bacteriuria in the neonates studied. The organisms encountered in this study were Escherichia coli (58.4%), Klebsiella species (35.3%) and Proteus species (5.9%). Of the bacterial isolates, 67% were sensitive to Ampicillin and 97% to Gentamycin. The combination of these antibiotics was effective in all cases in the present study. The study has highlighted the need for routine urine culture in our high risk neonates. PMID- 2919530 TI - Controlled versus hyperemic flow during reperfusion of jeopardized ischemic myocardium. AB - Controlled versus uncontrolled reperfusion of ischemic myocardium after experimental coronary artery occlusion was studied to determine the effect on regional ventricular wall motion and associated biochemical alterations. Fourteen pigs underwent coronary artery occlusion for 1 hour followed by 2 hours of reperfusion. In seven animals uncontrolled reperfusion was achieved by complete release of the arterial occlusion resulting in hyperemic flow. In seven other animals coronary flow during reperfusion was controlled at baseline levels eliminating hyperemic flow. Our results show that controlled reperfusion lessens end-diastolic wall thickness, reduces myocardial calcium deposition, increases the rate of mitochondrial oxidative phosphorylation, and preserves cellular high energy phosphate stores in the ischemic-reperfused myocardium when compared to the uncontrolled reperfusion state. These data suggest that the magnitude of flow at an early stage of reperfusion is one of the important determinants in the outcome of ischemic myocardium. PMID- 2919531 TI - Influence of leukopenia on collateral flow, reperfusion flow, reflow ventricular fibrillation, and infarct size in dogs. AB - Leukocytes contribute to myocardial damage during ischemia and reperfusion. However, the mechanism involved has not been clearly elucidated. The purpose of the present study was to determine whether leukocyte-induced myocardial damage is flow mediated. In open-chest dogs submitted to 2 hours of ischemia, area at risk, infarct size, and regional myocardial blood flow before, during, and after ischemia were measured. Leukopenia was induced by a two-step method (chemotherapy and antineutrophil serum) in a group of 14 dogs as compared to a control group of 18 dogs. The relation of infarct size to the major determinants of infarct size was analyzed by uni- and multilinear regressions. Seven control dogs had ventricular fibrillation at reperfusion compared to one dog with leukopenia. In the group with leukopenia the mean infarct size was smaller (31.1 +/- 5.8% of area at risk) than in the control group (47.7 +/- 2.9, p = 0.02). In addition, the two multiple linear regression equations were significantly different (p = 0.01). Myocardial blood flow to the central ischemic zone did not change significantly between 20 and 120 minutes of ischemia in the control dogs (n = 12; subendocardial = 0.08 +/- 0.03 vs 0.07 +/- 0.03 ml/min/gm; subepicardial = 0.20 +/- 0.07 vs 0.20 +/- 0.05 ml/min/gm) and in the dogs with leukopenia (n = 12; 0.07 +/- 0.02 vs 0.07 +/- 0.02 ml/min/gm and 0.15 +/- 0.004 vs 0.18 +/- 0.04 ml/min/gm). A similar reduction in myocardial blood flow was observed after 6 hours of reperfusion in the control dogs (0.34 +/- 0.07 ml/min/gm vs 1.02 +/- 0.11 at baseline, p less than 0.01) and in the dogs with leukopenia (0.25 +/- 0.04 vs 0.81 +/- 0.08 ml/min/gm, p less than 0.01). It was concluded that the leukocyte-dependent myocardial injury did not appear to be mediated through a flow mechanism during either ischemia or reperfusion. PMID- 2919532 TI - Long-term stepwise sustained improvement in left ventricular ejection fraction after myocardial infarction. AB - Radionuclide left ventricular ejection fraction, end-diastolic volume, and exercise capacity were determined in 34 selected patients who survived a first Q wave anterior infarction. Patients were included in the study if they had no subsequent cardiac events (unstable angina or myocardial infarction) during the average follow-up period of 47 months (range = 36 to 70 months); none was treated with thrombolysis, coronary angioplasty, or bypass grafting. Overall, mean left ventricular ejection fraction increased from 28 +/- 10% 1 month after infarction to 33 +/- 10% at 3 years (p less than 0.01); mean end-diastolic volume decreased from 217 +/- 99 ml to 171 +/- 80 ml (p less than 0.002). Stepwise improvement in left ventricular ejection fraction occurred in 15 of these patients (group B) and was associated with a significant increase in exercise capacity. Mean ejection fraction in group B was 26 +/- 7% at 1 month and 41 +/- 10% at 3 years (p less than 0.001). In all of these patients there was improved regional wall motion in the noninfarct zone, whereas five patients also showed improvement in the infarct zone. The results indicate a progressive improvement in left ventricular function that occurs over time in some patients after first Q wave anterior infarction, independent of intervention. PMID- 2919533 TI - Asymptomatic left main coronary artery disease and silent myocardial ischemia. AB - Gathering data on the prognosis, detection, and natural history of asymptomatic left main coronary artery disease with silent myocardial ischemia is difficult. Epidemiologic studies of unexpected death and postmortem studies on silent myocardial infarction suggest this entity to be common. We reviewed 89 consecutive patients with left main coronary artery disease (LMD), defined as 50% or greater reduction of luminal diameter. Of this group, 10 patients (11%) were asymptomatic (ALMD) and 79 patients (88%) were symptomatic (SLMD). All 10 ALMD patients were men, with a mean age of 53 years (range 40 to 65). Treadmill tests (TMT) were performed for: ECG abnormalities six; pre-jogging evaluation two; risk factor evaluation two. The TMT within 9 minutes showed 2 mm or greater ST depression in seven (70%) and 1 to 2 mm in three (30%). Similar TMT results were obtained in the SLMD group, although two patients had negative responses. The degree of stenosis of the left main coronary artery and the frequency of three vessel disease were similar in both groups. The ejection fraction (EF) and contractile pattern of the left ventricle (LV) were normal in all 10 ALMD patients, but the left ventricular end-diastolic pressure (LVEDP) was abnormal in three (70%). In the SLMD group, 51 (64%) had an abnormal ejection fraction, 50 (65%) had wall motion abnormalities, and 25 (32%) had an abnormal LVEDP. PMID- 2919534 TI - The impact of age on the incidence and prognosis of initial acute myocardial infarction: the Worcester Heart Attack Study. AB - As part of a community-wide study examining time trends in the incidence and case fatality rates (CFR) of patients hospitalized with acute myocardial infarction (MI) in sixteen hospitals in the Worcester, Massachusetts metropolitan area, the association of age to the incidence rates of initial acute MI and to in-hospital and long-term survival among 2115 patients with validated acute MI was examined. After selected age-specific changes in the incidence rates of initial events of acute MI between 1975 and 1981, the incidence rates of acute MI markedly declined between 1981 and 1984, resulting in decreases in the age-specific incidence rates of initial acute MI between 1975 and 1984. For the combined study periods, the in hospital CFR of acute MI increased from 5.0% in patients less than 55 years of age to 7.9% in those 55 to 64 years, to 16.1% in those 65 to 74 years and to 32.1% in patients 75 years of age and older. Among discharged hospital survivors, increasing age was related to poorer long-term survival over a 5-year follow-up period. The results of this population-based study reinforce the need for, and importance of, modification of coronary risk factors in both young and older individuals, and of focused therapeutic efforts to salvage jeopardized myocardium in elderly patients hospitalized with acute MI. PMID- 2919535 TI - Efficacy, safety, and tolerance of d-sotalol in patients with refractory supraventricular tachyarrhythmias. AB - The efficacy, safety, and electrophysiologic effects of intravenous and oral d sotalol, an investigational class III antiarrhythmic agent, are not yet well characterized. We evaluated the electrophysiologic, antiarrhythmic, and hemodynamic effects of d-sotalol infusion (1.5 to 2.75 mg/kg) and of chronic oral therapy (200 to 400 mg bid) in 10 patients with chronic, paroxysmal supraventricular tachyarrhythmias refractory to 5 +/- 2 standard agents. Four patients had paroxysmal supraventricular tachycardia (PSVT), four had paroxysmal atrial fibrillation, two had atrial flutter, and one had nonparoxysmal reciprocating junctional tachycardia (NPRJT). PSVT was inducible or spontaneously present in 4 of 4 before d-sotalol. After intravenous d-sotalol PSVT was noninducible in three patients and slowed by 40% in one. Atrial fibrillation was inducible or spontaneously present in 4 of 4 before therapy. After intravenous d sotalol, one became noninducible, and three achieved rate-slowing (the mean falling from 69 to 61 bpm). In one patient, atrial flutter became noninducible; in another, d-sotalol slowed the rate of atrial flutter by 28%. D-sotalol restored sinus rhythm in the patient with NPRJT. Intravenous d-sotalol increased the sinus cycle length; the QTc, PR, and AH intervals; and the AV nodal functional refractory period, the AV nodal effective refractory period; and the right ventricular effective refractory period significantly. The atrial effective refractory period, sinoatrial conduction time, and corrected sinus recovery time tended to increase, but did not reach statistical significance. The QRS, PA, and HV intervals did not change. Mean BP fell 13.4 +/- 9.2% after intravenous d sotalol, but no adverse symptoms developed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2919536 TI - Effect of calcium channel blockers on hemodynamic responses to defibrillation. AB - The hemodynamic response to sequences of ventricular fibrillation and defibrillation includes an adrenergic component that is important for the maintenance of blood pressure after successful defibrillation. Because calcium channel blocking drugs have antiadrenergic effects, we hypothesized that they might blunt the adrenergic response to defibrillation. Ventricular fibrillation was induced in 35 closed-chest dogs. Each received 4 to 7 direct current transthoracic shocks at three energy levels to determine defibrillation energy requirements. Heart rate and blood pressure were recorded. Energy sequences were repeated after 45 minutes of no intervention (control, n = 5) or after 45-minute infusions of diltiazem (0.1 mg/kg/min, n = 10), verapamil (0.1 mg/kg bolus plus 0.01 mg/kg/min, n = 10), or nifedipine (40 micrograms/min for 3 minutes plus 2 to 20 micrograms/min adjusted to maintain a 10 mm Hg drop in mean arterial pressure, n = 10). Our results show that the normal post-shock rise in mean arterial pressure was blunted by the calcium channel blockers diltiazem (systolic arterial pressure at 15 and 60 seconds post-shock, pre-drug versus post-drug: 102 +/- 9 versus 64 +/- 9 mm Hg and 113 +/- 10 versus 87 +/- 6 mm Hg; p less than 0.05) and verapamil (108 +/- 9 versus 78 +/- 12 mm Hg and 113 +/- 7 versus 90 +/- 10 mm Hg, p less than 0.05). There were no differences in blood pressure responses after nifedipine treatment or no drug. Heart rate responses were not altered by diltiazem or verapamil; after nifedipine administration, post-shock heart rates were slower.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2919537 TI - The effect of drugs and lead maturation on atrial electrograms during sinus rhythm and atrial fibrillation. AB - Antitachycardia devices need more accurate means to identify arrhythmias. Previous studies have found that sinus rhythm can be distinguished from a variety of tachyarrhythmias by algorithms that are based on time-domain and frequency domain analysis of intracardiac electrograms. Amplitude distribution analysis (time-domain) and power density spectral analysis (frequency-domain) are two of the techniques that have seemed to hold promise. However, previous studies have not evaluated whether lead maturation or drugs such as lidocaine, propranolol, verapamil, or isoproterenol can interfere with the ability of these algorithms to distinguish among cardiac rhythms. In the present study, five dogs had permanent atrial pacing leads placed. On a series of days, recordings were made from the atrial leads during sinus rhythm and induced sustained atrial fibrillation, both before and after administration of cardioactive drugs. For up to 1 month after implantation, progressive lead maturation did not prevent differentiation of atrial fibrillation from sinus rhythm by either amplitude distribution analysis or power density spectral analysis. However, the difference between the power density spectra of sinus rhythm and atrial fibrillation became progressively less with time. Isoproterenol, lidocaine, verapamil, and propranolol had no consistent effects on amplitude distribution analysis of atrial electrograms during sinus rhythm or atrial fibrillation. However, there were marked effects of drugs on amplitude distribution characteristics in individual dogs. Propranolol and lidocaine produced consistent changes in power density spectra during sinus rhythm and atrial fibrillation, respectively; both drugs reduced the ability of power density spectral analysis to differentiate sinus rhythm from atrial fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2919538 TI - Prediction of left ventricular ejection fraction using a unique method of chest x ray and ECG analysis: a noninvasive index of cardiac performance based on the concept of heart volume and mass interrelationship. AB - A reasonably accurate, simple, inexpensive, noninvasive method of determining ejection fraction (EF) is necessary to evaluate left ventricular function in epidemiologic studies and individual patients. Using the concepts of left ventricular mass reflected by precordial R wave summation (M) and left ventricular volume (V) estimated by chest roentgenography in 114 patients with myocardial disease undergoing left ventriculography, EF was predicted with the formula: EF = 63.74 - (2.16.V) + (0.34.M); R2 = 0.69; standard error of the estimate (SEE) = 11. Because angiographic inferior wall motion (IWM) abnormalities significantly affected the results, but inferior Q waves were usually only present in patients having one infarct, a noninvasive technique to predict the presence of inferior wall motion abnormality (IMA) in patients having multiple infarcts was developed and based on the relationship of precordial R wave summation (M) and roentgenographic heart volumenometry (V). By combining V, M, and IMA (which predicted IWM) to determine EF, multiple linear regression analysis showed that EF = 67.30 - (1.56.V) + (0.23.M) - (14.18 IMA) (R2 = 0.77; SEE = 9). Prospective validation of the formula was then done in 139 consecutive individuals, with R2 = 0.49 and SEE = 9. This study demonstrates that routinely performed, simple, inexpensive clinical tests provide data that can be combined by multiple regression analysis to predict resting EF in patients with heart disease affecting the left ventricle. This unique method may allow inexpensive ventricular function screening in large population studies and in addition might provide an independent index of myocardial performance for clinical use, since it reflects the amount of contractile mass per unit of left ventricular volume.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2919539 TI - Lens changes and the incidence of cardiovascular events among persons with diabetes. AB - Previous analysis of data from the Framingham Heart Study and the Framingham Eye Study showed that the "all-cause" death rate for diabetic persons with lens opacities was more than twice that of diabetic persons without lens opacities. Additional follow-up information was used to investigate whether these lens changes were associated with cardiovascular morbidity and mortality in particular. At the eye examination (1973 to 1975) there were 133 diabetic persons with no cardiovascular disease, of whom 41% had lens changes. Of these 133 persons, 57 had at least one cardiovascular event by the time of the most recent follow-up examination (1981 to 1983). Regression analyses suggested an increased risk of cardiovascular events among diabetic persons with lens changes (incidence rate ratio = 1.8; p = 0.07). Specifically there were associations of lens changes with the development of congestive heart failure (incidence rate ratio = 3.6; p = 0.01) and coronary heart disease (incidence rate ratio = 2.4; p = 0.08). Thus lens changes, in addition to being early prognostic signs of mortality, appear to be predictors of cardiovascular disease in adult-onset diabetes. PMID- 2919540 TI - Population screening for plasma cholesterol: community-based results from Connecticut. AB - Plasma cholesterol levels were measured in 15,892 participants of a cholesterol screening in Hartford, Connecticut. The screenees were typically health conscious as evidenced by the low prevalence of current cigarette smoking (12%). However, more than 25% of the men and 35% of the women over the age of 50 years had cholesterol levels in excess of 240 mg/dl, placing them at moderate to high risk for coronary artery disease. Results showed a pronounced dose-response relationship between cigarette smoking and cholesterol levels in men of all age groups and in women of premenopausal age; however, average cholesterol levels were similar in exsmokers and subjects who had never smoked. Risk analysis revealed a strong positive association between cholesterol and prevalence of nonfatal myocardial infarctions. Notably patients with newly diagnosed hypercholesterolemia reduced their cholesterol levels an average of 40 mg/dl under the care of a physician. These results indicate that cholesterol screening coupled with physician follow-up and treatment can have a substantial impact in lowering cholesterol levels and the attendant risk of cardiovascular disease. PMID- 2919542 TI - Percutaneous balloon valvuloplasty via the right internal jugular vein for valvular pulmonic stenosis with severe right ventricular failure. PMID- 2919541 TI - Balloon mitral valvuloplasty via retrograde left atrial catheterization. AB - A technique for performing retrograde catheterization of the left atrium followed by double balloon mitral valvuloplasty without transseptal catheterization is described. Three patients have undergone double balloon mitral valvuloplasty by means of this technique, all with marked improvement in postdilatation mitral valve areas. The technique avoids iatrogenic atrial septal defects and is less difficult to perform than transseptal catheterization. PMID- 2919543 TI - Endomyocardial trauma during balloon mitral valvuloplasty. PMID- 2919544 TI - Pathology of aortic valvuloplasty: findings after postmortem successful and failed dilatations. PMID- 2919545 TI - Detection of aortic valve ring abscess by intraoperative epicardial two dimensional echocardiography. PMID- 2919546 TI - Echocardiographic detection of abnormal attachment of a Bjork-Shiley prosthesis to the interatrial septum causing an atrial septal aneurysm. PMID- 2919547 TI - Aortico-left ventricular tunnel: two-dimensional echocardiographic and angiocardiographic features. PMID- 2919548 TI - Atrial automatic tachycardia with two different types of electrophysiologic characteristics. PMID- 2919549 TI - Intravenous dipyridamole: body weight considerations and dosage requirements. PMID- 2919551 TI - Modern methods of investigating converting enzyme inhibition. Satellite symposium to the Xth Congress of the European Society of Cardiology. August 28 to September 1, 1988, Vienna. Proceedings. PMID- 2919550 TI - The clinical description of angina pectoris in the elderly. PMID- 2919552 TI - Double-blind crossover versus parallel groups in hypertension. AB - The efficacy of antihypertensive drugs requires evaluation in clinical trials, the design of which must minimize variability (observer or patient) and order effects, eliminate bias, and include sufficient numbers of patients (i.e., have sufficient power) to allow real differences in blood pressure between patient groups to be detected at conventional levels of statistical significance. The crossover design of trial requires the successive examination of different treatments. This may result in a lengthy trial for the participant and an increase in the dropout rate. Therefore the parallel group design is usually performed for a comparison of several active drugs or drugs and placebo. This design avoids the potential problems of order and carryover effects, and when of a long duration, takes into account short-term and longer term responses to drugs. Crossover trials with limited periods of treatment for each phase can be carried out with fewer numbers of subjects and are more economical of patient resources. However, care must be taken to correct for order effects by appropriate design and to exclude carryover effects. Usually such a design only allows the investigator to comment on short-term blood pressure responses. The extrapolation of such information for longer term use of the drugs in clinical practice requires much caution. PMID- 2919554 TI - Congestive heart failure--advances in treatment. Introduction. PMID- 2919553 TI - Pharmacokinetics of a new angiotensin-converting enzyme inhibitor, benazepril hydrochloride, in special populations. AB - To investigate the pharmacokinetics of benazepril hydrochloride in special populations, single or multiple doses between 5 and 20 mg of the new drug were given, and the pharmacokinetics of unchanged benazepril and its pharmacologically active metabolite benazeprilat were compared with those in healthy male volunteers. In elderly subjects and patients with mild and moderate renal insufficiency, there was little change in the kinetics of benazepril or benazeprilat. In patients with severe renal impairment (creatinine clearance less than 30 ml/min), benazeprilat elimination was slowed, which resulted in greater accumulation after repeated dosing. In patients with hepatic cirrhosis, the kinetics and bioavailability of benazeprilat were not affected. Therefore dose adjustment is unnecessary because of the patient's age, mild or moderate renal impairment, or hepatic cirrhosis. Dose reduction is necessary in patients with creatinine clearance less than 30 ml/min. PMID- 2919555 TI - Evolution of left ventricular function after intracoronary thrombolysis for acute myocardial infarction. AB - The temporal evolution of left ventricular (LV) function after intracoronary streptokinase therapy for acute myocardial infarction (AMI) was assessed from the data of 264 patients who had complete occlusion of either the left anterior descending or the right coronary artery before treatment. Angiography was performed immediately, and at 3 days and 6 months after AMI in 91%, 71% and 47% of the study group, respectively. Wall motion was measured by the centerline method. In patients with sustained reperfusion, the ejection fraction decreased at 3 days (delta = -2.0 +/- 9.9%, n = 134, p = 0.02) and recovered later (from 54 +/- 12% acutely to 57 +/- 12% at 6 months, n = 82, p less than 0.05). These changes in global function were associated with a marked regression in hyperkinesis in the noninfarcted wall by 3 days, and delayed recovery of wall motion in the infarct region (delta = 0.2 +/- 0.9 at 3 days, p = 0.055; 1.0 +/- 1.2 at 6 months, p less than 0.001). Patients without reperfusion or with reocclusion had a more severe decrease in ejection fraction at 3 days, and little or no subsequent functional recovery. The length of the hypokinetic segment increased significantly by 3 days but subsequently diminished to slightly less than the acute value. It is concluded that full recovery of ischemically impaired myocardium takes greater than 3 days, but compensatory hyperkinesis regresses earlier so that global LV function deteriorates by the third day. Variability or deterioration of LV function early after AMI need not be due to infarct extension; it can reflect regression of hyperkinesis in the noninfarcted region. PMID- 2919556 TI - Low vitamin B6 status in patients with acute myocardial infarction. AB - The vitamin B6 status of 84 patients with acute myocardial infarction was compared with that of 84 control subjects. Pyridoxal and pyridoxal 5'-phosphate (PLP) in plasma and erythrocytes, as well as the basal and total potential activity of the PLP-dependent enzyme aspartate aminotransferase in erythrocytes, were measured for a comprehensive assessment of vitamin B6 status. The mean levels of all vitamin B6 indexes (except pyridoxal) were lower in the patients than in the control subjects. The differences were statistically significant, except for erythrocyte PLP and total potential enzyme activity. The adjusted relative odds of a myocardial infarction for subjects in the lowest quartile of plasma PLP was about 5 times higher when compared with those in the highest quartile (relative odds = 5.2, 95% confidence interval = 1.4 to 18.9). Similar findings were found with the other vitamin B6 indexes. No significant association between infarct size, as estimated by creatine kinase level, and the vitamin B6 indexes was observed. PMID- 2919557 TI - Clinical and hemodynamic significance of left ventricular diastolic volume changes by exercise radionuclide ventriculography in coronary artery disease. AB - Recent studies have suggested that left ventricular (LV) dilatation during exercise radionuclide ventriculography may identify coronary artery disease (CAD). Coronary anatomy and LV end-diastolic pressure at catheterization were compared with results of supine exercise radionuclide ventriculography in 66 patients evaluated for chest pain. Forty-six patients had significant CAD (greater than 75% diameter stenosis) and 20 patients were normal. Radionuclide ventriculography was performed within 18 hours of catheterization, at rest and at peak exercise. Relative LV end-diastolic volumes were extrapolated from end diastolic counts. LV end-diastolic counts increased during exercise in 19 of 20 normal subjects. In patients with CAD, LV end-diastolic counts increased in 35 (group A) and decreased in 11 (group B). The percent change in LV end-diastolic counts from rest to exercise, rest ejection fraction, exercise ejection fraction and rest LV end-diastolic pressure for each group were 20 +/- 23%, 60 +/- 13%, 67 +/- 13% and 8 +/- 3 mm Hg in normal subjects; 20 +/- 20%, 50 +/- 12%, 47 +/- 13% and 12 +/- 4 mm Hg in group A; and -9 +/- 8%, 54 +/- 21%, 49 +/- 18% and 21 +/- 7 mm Hg in group B (mean +/- standard deviation). An increase in LV end-diastolic counts was unrelated to ejection fraction response or presence of underlying CAD but only correlated to rest LV end-diastolic pressure (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2919558 TI - Electrophysiologic manifestations of the excitable gap of orthodromic atrioventricular reciprocating tachycardia demonstrated by single extrastimulation. AB - To assess the electrophysiologic characteristics of the excitable gap, 12 patients with orthodromic atrioventricular (AV) reciprocating tachycardia were studied. During tachycardia, 8 patients used a left-sided and 4 patients a right sided anomalous bypass tract for retrograde conduction. QRS complex-synchronized single extrastimuli were delivered from high right atrium, right ventricular apex and coronary sinus, respectively, scanning the whole cycle length of tachycardia. An excitable gap was determined to be present if tachycardia resetting or tachycardia termination occurred. The duration of the excitable gap varied among different pacing sites and occupied 0 to 48% (mean 17 +/- 16) of basic tachycardia cycle length (240 to 480 ms, mean 327 +/- 70). Three patterns of tachycardia resetting were observed: the sum of coupling interval and return cycle being (1) less than a fully compensatory pause in 12 of 12 patients, (2) more than a fully compensatory pause in 5 of 12 patients and (3) equal to a fully compensatory pause in 2 of 12 patients, depending on extent of AV nodal conduction delay exhibited in return cycle. Tachycardia termination was possible when extrastimuli were delivered from right ventricular apex and coronary sinus but not from high right atrium, and only when basic tachycardia cycle length was greater than or equal to 290 ms in 7 of 12 patients. Tachycardia termination was accounted for by development of orthodromic conduction block in AV node in 7 of 7 patients and in bypass tract in 2 of 7 patients. Therefore, site of extra stimulation and basic tachycardia cycle length affect electrophysiologic manifestations of excitable gap. Further, functional properties of the AV node influence patterns of tachycardia resetting and are primarily responsible for tachycardia termination during programmed single extrastimulation. PMID- 2919559 TI - Importance of the endpoint of noise reduction in analysis of the signal-averaged electrocardiogram. AB - Reduction of random noise by signal averaging is required to uncover ventricular late potentials (LPs). Noise reduction is dependent upon the ambient noise before the study and the number of signal-averaged QRS complexes. Prior studies have used a fixed number of QRS complexes (e.g., 150 to 200) for performing signal averaged electrocardiograms (SAECGs). Because of variable background noise levels, it was hypothesized that variable noise levels after processing could interfere with detection of LP. Accordingly, SAECGs were performed for each patient to 2 prespecified noise endpoints (expressed as the standard deviation/square root of number of beats): 1.0 microV, which has been used previously as a minimal residual noise level, and 0.3 microV, a low level that generally can be attained in less than 450 beats. Root mean square-voltage noises in the 40-Hz high pass filtered vector magnitude for these studies were 1.36 +/- 0.57 and 0.58 +/- 0.28 microV, respectively. The relative prevalence of LP was evaluated in 3 groups. Group I was comprised of 26 patients with sustained ventricular tachyarrhythmias, group II included 59 patients after myocardial infarction and group III had 14 normal volunteers. The prevalence of LP was greater in group I (69 vs 46%, p less than 0.001) and group II (34 vs 24%, p less than 0.01) with the 0.3-microV studies. In group III, the prevalence did not change (7 vs 7%, difference not significant). The greater detection of LP was due to improved resolution of the terminal low-amplitude QRS segment. Therefore, using the 0.3 microV level instead of 1.0 microV increased sensitivity of LP without loss of specificity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2919560 TI - Effect of disopyramide on initiation of atrial fibrillation and relation to effective refractory period. AB - Electrophysiologic studies were performed before and after intravenous administration of disopyramide (2 mg/kg) to 40 patients with either documented or suspected atrial fibrillation (AF). In control studies, sustained AF (greater than 1 minute), nonsustained AF (1 to 60 seconds) and no AF were found in 14, 18 and 8 patients, respectively. After disopyramide, the ability to initiate AF was totally lost in 18 patients (group A), while 22 patients (group B) showed sustained AF (11 patients) or nonsustained AF (11 patients). The effective refractory period of the atrium was 232 +/- 41 ms in the control study and 266 +/ 49 ms after disopyramide. Atrial functional refractory periods before and after disopyramide were 282 +/- 43 and 317 +/- 48 ms, respectively. The differences and ratios of the refractory periods after and before disopyramide were higher in group A than in group B (p less than 0.001). The prolongation of atrial refractoriness after disopyramide was important to suppress the initiation of AF in group A. In some group B patients, on the other hand, the initiation of AF was promoted after disopyramide. Disopyramide may alter the atrial electrophysiologic substrate required for AF initiation. PMID- 2919561 TI - Hemodynamic effects of pimobendan given orally in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. AB - Pimobendan (UD-CG 115 BS) was administered orally to 23 patients with congestive heart failure (functional class IV) caused by coronary artery disease (11 patients) or idiopathic dilated cardiomyopathy (12). All patients received maintenance doses of digoxin, furosemide and warfarin. Baseline data, collected during 15 hours, stayed within a 10% range. A 10-mg oral dose of pimobendan increased the heart rate from 95 +/- 20 to 109 +/- 24 beats/min (p less than 0.003). The pulmonary artery wedge pressure decreased from 23.0 +/- 5.9 to 10.1 +/- 5.2 mm Hg (p less than 0.0001), the cardiac index increased from 1.9 +/- 0.4 to 3.3 +/- 0.7 liters/min/m2 (p less than 0.0001) and the left ventricular stroke work index increased from 2,005 +/- 927 to 3,065 +/- 1,161 ml/mm Hg/m2 (p less than 0.0001). Statistically significant improvements in hemodynamic variables were still present 10 hours after the administration of pimobendan. Most patients felt better and reported no angina or other side effect, the incidence of ventricular arrhythmias was unchanged and no electrocardiographic changes suggesting ischemia were observed. Patients with severe congestive heart failure experienced a prolonged improvement of their cardiovascular condition after a single dose of pimobendan. PMID- 2919562 TI - Functional anatomy of severe mitral regurgitation in active rheumatic carditis. AB - The mechanism of severe mitral regurgitation (MR) due to active rheumatic carditis is ill defined. This study involved 73 patients, aged 7 to 27 years (mean 13), with severe MR and active rheumatic carditis who were subjected to surgery. Sixty-one were studied retrospectively (group 1) and 12 prospectively (group 2). Active rheumatic carditis was diagnosed according to the modified Jones' criteria, morphologic appearances of the heart at operation and histology of the valve. All patients had preoperative 2-dimensional echocardiographic and intraoperative assessment of the mitral valve apparatus. The presence of mitral valve prolapse--defined as failure of leaflet edge coaptation resulting in systolic displacement of the free edge of the involved leaflet toward the left atrium--was determined in all patients. Mitral anular diameter and maximal systolic chordal length were measured at 2-dimensional echocardiography in group 2 patients and compared to values obtained from matched control subjects. Anular and chordal dimensions in 6 of the group 2 patients were correlated with precise measurements obtained at surgery. Mitral valve prolapse involving the anterior leaflet was detected on echocardiography and confirmed at surgery in 69 patients (94%). Mitral anular dilatation was observed at operation in 70 patients (96%). Maximal anular diameter was significantly greater (p less than 0.0001) than in matched control subjects (37 +/- 4 vs 23 +/- 2 mm). The mean anular dimension measured at surgery (36 +/- 3 mm) was similar to that obtained by echocardiography and individual values using the 2 methods correlated well (r = 0.93). Chordal elongation was observed in 66 patients at operation (90%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2919563 TI - Efficacy of intraoperative transesophageal echocardiography in children with congenital heart disease. AB - The feasibility and potential adverse effects of using intraoperative transesophageal echocardiography (TEE) in 19 children ages 7.5 to 16 years undergoing surgical repair of a variety of congenital heart defects were evaluated. The ability of TEE to assess the adequacy of surgical repair as well as left ventricular function and wall motion abnormalities in this setting was also examined. Intraoperative transesophageal 2-dimensional and Doppler evaluation, and, in selected patients, echo-contrast and color flow imaging, were performed with either a 3.5- or 5.0-MHz phased array probe mounted within the tip of a flexible gastroscope. Probe insertion was successful in 18 of 19 patients. Fiberoptic endoscopy (9 patients) and autopsy (1 patient--cardiac donor) performed within 24 hours of surgery demonstrated no significant esophageal abnormalities. Intraoperative wall motion abnormalities were identified in 8 patients but did not persist after the operation. An adequate surgical repair was demonstrated by contrast and color flow imaging in most patients. Microcavitation was detected in 6 patients for greater than 5 minutes after a standard debubbling procedure. No patient displayed any adverse neurologic effects. It is concluded that, with the currently available probes, intraoperative TEE can be performed safely and reliably in children as young as 7.5 years of age. The procedure provides valuable information regarding wall motion abnormalities, cardiac function and the adequacy of surgical repair. PMID- 2919564 TI - Genetic factors in the electrocardiogram and heart rate of twins reared apart and together. AB - Important physiologic mechanisms have been thought not to exhibit large amounts of variability, due in part to the assumption that critical biologic functions will have evolved to an evolutionary optimum. The attainment of this optimum would necessarily eliminate individual differences in these variables. Using a sample of monozygotic and dizygotic twins reared apart since birth or early infancy, 12-lead electrocardiographic recordings and vectorcardiograms were obtained. Values of these variables for monozygotic and dizygotic twins reared together were obtained from other studies. Maximum likelihood tests of genetic and environmental components of variation for PR interval, QRS duration, QT interval and ventricular rate indicated a significant contribution of genetic effects (most heritabilities ranged from 30 to 60%), with a negligible contribution from common familial environmental effects. PMID- 2919565 TI - New coronary events at four-year follow-up in elderly patients with recognized or unrecognized myocardial infarction. PMID- 2919566 TI - Effect of acute systemic blood pressure elevation on left ventricular filling with and without mitral regurgitation. PMID- 2919567 TI - Radiographic pulmonary congestion in end-stage congestive heart failure. PMID- 2919568 TI - Operative results in endomyocardial fibrosis. PMID- 2919569 TI - Mitral and tricuspid valve regurgitation in dilated cardiomyopathy. PMID- 2919570 TI - The confusion technique untangled: its theoretical rationale and preliminary classification. AB - This article examines the historical development of Milton H. Erickson's theoretical approach to hypnosis using confusion. Review of the literature suggests that the Confusion Technique, in principle, consists of a two-stage "confusion-restructuring" process. The article also attempts to categorize several examples of confusion suggestions by seven linguistic characteristics: (1) antonyms, (2) homonyms, (3) synonyms, (4) elaboration, (5) interruption, (6) echoing, and (7) uncommon words. The Confusion Technique is an important yet little studied strategy developed by Erickson. More work is urged to investigate its nature and properties. PMID- 2919571 TI - Coping with examination stress through hypnosis: an experimental study. AB - Fifty-six volunteer medical students participated in three groups balanced for number of subjects, performance at last examination, and hypnotizability. The hypnosis and waking groups attended eight group sessions once a week with general ego-strengthening and specific suggestions for study habits, with a ninth session of age progression and mental rehearsal. Subjects in these two groups practiced self-suggestions (in self-hypnosis or waking respectively) daily for the study period of 9 weeks. The control group experienced sessions of passive relaxation induced by light reading for the same period of time. The hypnosis group improved significantly in coping with examination stress, but there was no significant change in performance on examinations by any of the groups. PMID- 2919572 TI - Hypnotic versus active cognitive strategies for alleviation of procedural distress in pediatric oncology patients. AB - This study provided a differential comparison of the efficacy of standardized instruction in hypnosis or active cognitive strategy for provision of relief from procedurally induced pain and anxiety. Subjects were instructed to self-direct in the use of strategies during medical procedures. Twenty pediatric oncology patients participated in the study. They were not informed that hypnosis was one of the strategies. Subjects were screened for hypnotizability and randomly assigned to treatments. Demographic data were collected. Pre-strategy training observations were made during a Bone Marrow Aspiration or Lumbar Puncture (BMA/LP) using visual analog scales, the McGill Pain Questionnaire, State-Trait Anxiety Inventory, pulse and temperature readings, and interview. Following strategy training, data were collected during a second BMA/LP using the same measures as employed pre-intervention. Results indicated that both strategies were effective in providing pain reduction. Neither technique provided for anxiety reduction. Hypnotizability scale scores failed to correlate with degree of pain reduction. PMID- 2919573 TI - Ego-enhancement: a five-step approach. AB - The present article describes an ego-enhancement procedure which combines hypnotic induction, trance deepening, positive suggestion, and imagery in a five step "package." This procedure may be used in a generalized form with no reference to the patient's presenting symptoms or it may be tailored to address specific problems. The elements comprising the "package" are: (1) physical relaxation, (2) mental calming, (3) disposal of mental "rubbish," (4) removal of a barrier representing everything that is negative in the life of the subject, and (5) enjoyment of a special place where the subject feels content. Opportunities to tailor the approach to handle specific problems occur within each of these five steps, particularly when patients are in their "special place." Three case studies are provided to indicate how such tailoring is done. PMID- 2919575 TI - Hypnosis: emotions for the tin man (the schizoid personality). AB - Insight psychotherapy had been ineffective in helping a schizoid patient experience affect. He remained cold, aloof, and without overt expression of affect. When hypnosis was utilized, the patient overtly demonstrated affect. Hence the title for the article--hypnosis was effective in changing the tin man into a person with emotions and feelings. A discussion indicates some possible variables associated with this phenomenon. PMID- 2919574 TI - The use of indirect hypnotic suggestions for insomnia arising from generalized anxiety: a case report. AB - This case report concerns an aggressive, independent, and financially successful businessman who suffered with insomnia within the context of generalized anxiety disorder. The hypnotherapy included indirect suggestions for the insomnia delivered through the vehicle of metaphorical stories designed as an indirect intervention for the generalized anxiety. The client's perception of the problem was clarified and respected, but the choice of intervention strategy was designed to indirectly suggest more global changes. The creative changes made by the client were positive and enduring at 2-year follow-up. PMID- 2919576 TI - Acute pregnancy-associated hypertension treated with hypnosis: a case report. AB - A 24-year-old patient was treated using hypnotic intervention for acute pregnancy associated hypertension. The patient displayed evidence of secondary arrest of labor and acute onset of signs and symptoms of pre-eclampsia. Hypnotic intervention resulted in normal vaginal delivery without complications or further evidence of morbidity secondary to a hypertensive episode. Hypnosis as an adjunct in the treatment of pre-eclampsia should be investigated further. PMID- 2919577 TI - Barrett's esophagus: what's new and what to do. PMID- 2919578 TI - Physician role model: past, present, and future. PMID- 2919579 TI - 1988 Henry Baker lecture. The community hospital gastroenterologist: survival of the species. PMID- 2919581 TI - Duodenal Crohn's disease: an analysis of 89 cases. AB - Duodenal Crohn's disease has an estimated incidence of 1% to 2% among patients with Crohn's disease. We report 89 patients with duodenal Crohn's disease. Common symptoms were upper abdominal pain and symptoms of gastroduodenal obstruction. Contiguous disease of the gastric antrum and duodenum was present in 60% of patients. Endoscopic examination revealed abnormalities in 62 of 67 patients. Granulomas or granulomatous inflammation was found in 37 of 76 patients. Forty nine patients treated medically were followed up for 2-25 yr (median 9.7 yr). Good to excellent results were obtained in 45 patients. Thirty-three patients required surgical intervention, usually for gastroduodenal obstruction. Reoperation was required in eight patients, seven of whom had had vagotomy with gastroenterostomy or subtotal gastrectomy. In two of these seven patients, marginal ulcers developed. Both patients had had gastroenterostomy and vagotomy. Our experience does not support the routine use of vagotomy when a bypass procedure is performed. Good to excellent results were achieved in 26 of the 30 surgically treated patients followed up for more than 1 yr (1-43 yr; median 11 yr). Measured in terms of need for surgical intervention, gastroduodenal disease generated considerably less morbidity than did distal Crohn's disease (p less than 0.001). Most patients achieved good to excellent results whether treated medically or surgically. PMID- 2919580 TI - In vivo susceptibility of Campylobacter pylori. AB - Campylobacter pylori infection has been associated with duodenal ulcer, gastric ulcer, and non-ulcer dyspepsia. Although in vitro studies have shown that C. pylori is susceptible to most commonly used antibiotics, predictions from in vitro sensitivity studies have not led to a safe and generally effective therapy; C. pylori has proved to be very difficult to eradicate in vivo. We used the urea breath test to assess the susceptibility of C. pylori in vivo to various drugs. C. pylori was susceptible to bismuth subsalicylate, bismuth subnitrate, and furazolidone. C. pylori was not susceptible (i.e., urease activity remained despite administration of the drug) to the following drugs: 1) antiulcer agents (cimetidine, ranitidine, famotidine, omeprazole, misoprostol, sucralfate, liquid antacids); 2) NSAIDs (aspirin, indomethacin, ibuprofen, naproxen, tolmetin); 3) antibiotics (oral penicillin V, trimethoprim-sulfamethoxazole, dicloxacillin); 4) salts (lithium, ferrous sulfate, gold); 5) miscellaneous (acetaminophen, phenytoin, hydrochlorothiazide, propranolol, metoprolol, metoclopramide, ursodeoxycholic acid). Oral antimicrobials can be administered directly onto the site of infection, so that a very low oral dose will provide many multiples of the in vitro minimal inhibitory concentration. Furazolidone suspension (7 mg) was administered seven times daily (daily dose 49 mg) to three individuals infected by C. pylori during suppression of gastric acid secretion with famotidine (40 mg bid). After 4 days, all subjects had significant reductions in urease activity (two to normal and one to a borderline value). This response suggested that very low-dose therapy may be useful either alone or combined with bismuth. Conclusive establishment of an etiologic (or major contributory) relationship of C. pylori to ulcer disease will require a safe and reliable method to eradicate the organism from the stomach and duodenum. PMID- 2919582 TI - Epidemiology of Crohn's disease in the Jewish population of central Israel, 1970 1980. AB - The epidemiology of Crohn's disease (CD) during the years 1970-80 was studied in the Jewish population in a defined area of central Israel with 1.4 million inhabitants. Three hundred sixty-five patients with definite CD were identified, and a complete follow-up was obtained. The incidence of CD rose from 0.33 (per 10(5)) in 1970 to 3.10 in 1979. This rise was noted in both sexes, in all age groups, in all major Jewish community groups, and was demonstrated in three different regions of the study area. It is thought to represent a true (10-fold) increase in incidence. The mean annual incidence was 1.55/10(5). The prevalence in 1970 was 7.08/10(5), and in 1980 it was 19.47/10(5). In 1970, the age-adjusted prevalence in immigrants from Europe-America was 13.27 and in immigrants from Asia-Africa it was 1.69. In 1980, the difference between the two groups narrowed and the prevalences were 26.05 and 12.37, respectively. This decrease in differences between original migrant groups, as well as the rapid changes in incidence, point to the effect of environmental factors in the pathogenesis of CD. Population studies worldwide have demonstrated an increased incidence of CD in Jews, with marked differences among Jews in different geographic areas. This suggests the coexistence of genetic and environmental factors in the pathogenesis of the disease. PMID- 2919583 TI - Pancreatic pseudocysts: clinical and endoscopic experience. AB - Records of 51 patients with proven pancreatic pseudocyst (PC) were retrospectively reviewed to assess clinical and endoscopic variables. Thirty-nine had surgery after preoperative endoscopic retrograde cholangiopancreatography (ERCP), six patients had ERCP only, and six patients had surgery without prior ERCP. Forty-two pancreatograms were obtained, and all were abnormal. PC communication with the pancreatic duct was present in 29 and ductal obstruction downstream from the PC was shown in 11 studies. Thirty-five cholangiograms were obtained and 19 were abnormal, including ductal narrowing in 16 and biliary calculi in three. PC contents were cultured intraoperatively in 29 patients, and 17 were positive. PC infection was highly correlated with the incidence of recurrent hospitalizations and with PC recurrence. PC infection did not occur significantly more often in patients with communicating PC or in those with preoperative ERCP. Factors that did not influence outcome included PC size, multiplicity, anatomic location, and PC communication with the pancreatic duct. Results from both ERCP and culture of PC contents add significantly to our knowledge of PC disease. PMID- 2919584 TI - Effect of renal prostaglandins on survival in patients with liver cirrhosis. AB - To assess the effect of renal prostaglandins on the prognosis of liver cirrhosis, we studied the relationship between the effect of prostaglandin synthetase inhibition by indomethacin on glomerular filtration rate (GFR) and effective renal plasma flow (RPF) and survival in 30 patients with liver cirrhosis. After indomethacin administration, GFR dropped significantly from 86 +/- 2 ml/min to 73 +/- 3 ml/min (p less than 0.01) and RPF from 421 +/- 10 to 349 +/- 14 ml/min (p less than 0.01). Survival was not correlated with baseline GFR or RPF, but was correlated with changes in both GFR and RPF after indomethacin administration (p less than 0.01). The cumulative survival rate from 1 to 7 yr was significantly higher (p less than 0.01) in patients with a decrease in GFR of less than or equal to 15% after indomethacin administration than in patients with a decrease in GFR of more than 15%. Findings for changes in RPF after indomethacin administration were similar. These results suggest that the augmentation of prostaglandin inhibition by indomethacin is associated with a poor prognosis of liver cirrhosis. It may be involved in the depletion of renal prostaglandins to maintain renal hemodynamics in patients with liver cirrhosis. PMID- 2919585 TI - The biotransformed metabolite profiles in blood after intravenous administration of dehydrocholic acid. AB - One gram of dehydrocholic acid was injected intravenously into two patients with percutaneous transhepatic cholangial drainage, and the biotransformed metabolites profiles over a 120-min period in serum and bile were analyzed. In serum unconjugated 3 alpha-hydroxy-7,12-dioxo-cholanoic acid (3 alpha-OH-7,12-OXO) acid was markedly increased after the injection of dehydrocholic acid, and reached about 80 microM within 30 min. On the other hand, conjugated 3 alpha, 7 alpha dihydroxy-12-oxo-cholanoic acid (3 alpha,7 alpha-OH-12-OXO) was consecutively increased with lag time to an elevation of 3 alpha-OH-7,12-OXO. In bile, the major constituent of metabolites was conjugated 3 alpha,7 alpha-OH-12-OXO (more than 90% of the excreted metabolites), while conjugated 3 alpha-OH-7,12-OXO was detected as minor constituent. Therefore, between bile and serum, there was great difference in biotransformed metabolites profiles. The mechanism of elevation of unconjugated 3 alpha-OH-7,12-OXO in serum remains obscure, but this new finding raised a question as to whether organ-reducing 3-keto group of dehydrocholic acid is restricted to the liver. PMID- 2919586 TI - Measurement of portal shunting in dogs. AB - A new method for measuring the quantity of portal blood bypassing the liver (shunted) has been developed and tested in the dog. Shunts were mimicked by the simultaneous infusion of glycocholic acid into a small peripheral portal venule and a peripheral vein. The total infused amount was kept constant, but the ratio at the two infusion sites varied. Determination of the extraction efficiency of the liver by simultaneously measuring the hepatic vein and arterial blood for systemically infused [14C]glycocholic acid permitted the calculation of shunted blood from information provided by the concentration of glycocholic acid in the hepatic vein, artery, and portal vein blood. This method was tested for various proportion of shunting from none to complete. The total hepatic flow was determined with single injection of indocyanine green and the individual arterial and portal vein flows determined with flowmeters. The input ratios of shunting related quite closely to that calculated from the flowmeters or the hepatic extraction ratio. PMID- 2919587 TI - Long-term survival after an end-to-side portacaval shunt. PMID- 2919588 TI - Development of splenoadrenorenal shunts after obliteration of esophageal varices by endoscopic sclerotherapy. AB - We present three patients with portal hypertension in whom large splenoadrenorenal shunts developed after obliteration of esophageal varices by endoscopic sclerotherapy. PMID- 2919589 TI - Prosthetic endocarditis after endoscopic variceal sclerotherapy: a failure of antibiotic prophylaxis. AB - Bacteremia after esophagogastroduodenoscopy and endoscopic procedures such as esophageal variceal sclerotherapy is well recognized. The theoretical risk of endocarditis has led the American Heart Association and other authorities to recommend antibiotic prophylaxis for these procedures. However, no well documented episodes of endocarditis associated with endoscopy have been reported. The current case of prosthetic valvular endocarditis is clearly linked to endoscopic sclerotherapy and occurred despite such antibiotic administration. This failure of prophylaxis may be due to factors specific to this patient; however, the efficacy of prophylaxis remains to be proven. PMID- 2919590 TI - Detection of human immunodeficiency virus-1 by 35S-RNA in situ hybridization in solitary esophageal ulcers in two patients with the acquired immune deficiency syndrome. AB - Esophageal disease frequently complicates the course of the acquire immune deficiency syndrome. In two patients with unusual refractory esophageal ulcers, we were able to demonstrate the presence of human immunodeficiency virus RNA in lymphocytes and mononuclear cells from the ulcer base, using an in situ hybridization technique. These observations suggest that human immunodeficiency virus may play a role in the development or persistence of solitary refractory esophageal ulcers. PMID- 2919591 TI - Kaposi's sarcoma with visceral involvement in a young heterosexual male without evidence of the acquired immune deficiency syndrome. AB - A case of disseminated Kaposi's sarcoma (KS) in a 21-yr-old white heterosexual male with cryptogenic cirrhosis and no serological or immunological evidence of acquired immune deficiency syndrome (AIDS) is reported. The patient died 2 wk after diagnosis. Postmortem examination showed involvement of lymph nodes, liver, spleen, gastrointestinal tract, and bone marrow. This case demonstrates that Kaposi's sarcoma can occur in a young heterosexual male with normal immune function and in the absence of HIV infection. PMID- 2919592 TI - A case of Behcet's disease with intestinal involvement due to Crohn's disease. AB - A 15-yr-old, Arabic male presented with painful, recurrent, self-resolving oral and genital ulcers, erythema nodosum and uveitis. Behcet's disease was diagnosed. A few months later, he experienced anorexia, abdominal pain, diarrhea, and weight loss. Although all routine laboratory and radiologic investigations were negative, colonoscopy revealed the presence of serpiginous ulcers with pseudopolyps and inflamed intervening mucosa in the proximal half of the colon. Therapy with oral steroids was helpful, but the disease exacerbated a few months after prednisone was discontinued. Repeat evaluation showed similar endoscopic findings and, on colonic biopsy, noncaseating granulomas compatible with Crohn's disease were seen. Again, the patient responded well to oral steroids and sulfasalazine. We believe that gastrointestinal involvement in our patient is compatible with Crohn's disease and that screening tests to rule out chronic inflammatory bowel disease should be performed in the presence of gastrointestinal involvement in Behcet's disease. Behcet's disease may be a part of the spectrum of chronic inflammatory bowel disease. PMID- 2919593 TI - Short-term administration of SMS 201-995 in the management of an external pancreatic fistula. AB - A patient presented to the hospital with a persistent high-output (greater than 250 ml/day) external pancreatic fistula after an enucleation of an insulinoma 5 months earlier. Daily treatment with SMS 201-995, a long-acting somatostatin analogue, for 8 days decreased fistulous output to less than 5 ml/day. The patient was discharged in stable condition 9 days after admission. All drainage ceased 2 days later, and the fistula has remained closed. SMS 201-995 has been shown to be effective in decreasing fistulous output of external pancreatic fistulas of various origins. With its few side effects and remarkable effectiveness, SMS 201-995 should be considered in the conservative management of any external pancreatic fistula. PMID- 2919594 TI - Response to W. Scott Brooks, Jr., on prophylactic sclerotherapy. PMID- 2919595 TI - Acute calcular cholecystitis associated with Brucella melitensis. PMID- 2919596 TI - Pseudochylous ascites developed in a patient with chronic renal failure: importance of lipoprotein analysis. PMID- 2919597 TI - Penile metastases from esophageal carcinoma. PMID- 2919598 TI - Rifampin as antipruritic agent in primary sclerosing cholangitis. PMID- 2919599 TI - Acute renal failure associated with ioxaglate, a low-osmolality radiocontrast agent. AB - Iodinated radiocontrast agents may cause acute renal failure, particularly in patients with preexisting renal failure, heart failure, or diabetes. The low osmolality contrast agents cause less hypersensitivity, but substantial nephrotoxicity has not been noted. We report three high-risk patients who developed acute renal failure after one of these new agents, ioxaglate, was administered for coronary arteriography and ventriculography. The renal failure was severe: two of the patients required dialysis. We could find no previously reported cases of acute renal failure associated with ioxaglate. Despite their theoretical advantages, the low-osmolality contrast agents may cause acute renal failure in patients who are at risk and should be used with the same precautions as the conventional agents. PMID- 2919600 TI - Phosphate-binding effects of sucralfate in patients with chronic renal failure. AB - Sucralfate has been reported to reduce serum phosphate concentration in patients with chronic renal failure. To evaluate whether sucralfate could be used to treat hyperphosphatemia secondary to chronic renal failure and whether this treatment resulted in a reduced exposure to aluminum, an open-label crossover study was designed to determine the efficacy, relative potency, safety, and cost of sucralfate v aluminum hydroxide. Of the 21 hemodialysis patients completing both phases of the crossover study, serum phosphate could be maintained below 4.5 mg/dL (1.45 mmol/L) in 16 with sucralfate and in 14 with aluminum hydroxide. The 16 patients controlled on sucralfate consumed 1,694 +/- 190 mg/d of aluminum to maintain a serum phosphate concentration of 3.91 +/- 0.17 mg/dL (1.27 +/- 0.05 mmol/L) compared with the 14 patients controlled on aluminum hydroxide with an aluminum intake of 2,678 +/- 294 mg/d (P less than 0.025) and a serum phosphate concentration of 3.94 +/- 0.13 mg/dL (1.27 +/- 0.04 mmol/L). Thus sucralfate was an effective, albeit expensive, alternative to aluminum hydroxide for the treatment of hyperphosphatemia associated with chronic renal failure. Although the difference in aluminum intake was significant, use of sucralfate did not result in lower serum aluminum concentrations. PMID- 2919601 TI - The protective mechanism of thyroidectomy in a rat model of chronic renal failure. AB - Selective thyroidectomy (Tx) has been shown to attenuate proteinuria and disease progression in models of chronic renal failure (CRF). In this investigation, four groups of Munich-Wistar rats were studied to determine if glomerular dynamics or another renal metabolic consequence of Tx was responsible for the protective effect as measured by 24-hour protein excretion (UPROT). The groups were TxT4, thyroxine-replaced Tx rats with five-sixths nephrectomy; Tx, Tx rats not receiving replacement thyroxine with five-sixths nephrectomy; TxI, Tx rats not receiving replacement thyroxine with five-sixths nephrectomy that were given continuous intraperitoneal isoproterenol to restore systemic and renal hemodynamics; and TxT4(C), two-kidney Tx rats receiving replacement thyroxine that served as normal controls. Five-sixths nephrectomy was carried out 2 weeks after Tx, and experiments were carried out 1 week later. Serum T4 was profoundly reduced and there was failure to gain weight in Tx and TxI rats, despite similar protein intakes in all groups. Cardiac output was reduced in Tx, but was similar in TxI to levels in TxT4 rats. Whole-kidney glomerular filtration rate was lower in Tx, at 0.145 +/- 0.052 mL/min (P less than 0.05), but similar in TxI (0.305 +/ 0.147 mL/min) to that in TxT4 rats (0.317 +/- 0.135 mL/min). Twenty-four-hour urinary protein, which was 129 +/- 57 mg in TxT4, was reduced in Tx to 9 +/- 3 mg (P less than 0.01) but restored in TxI to 89 +/- 30 mg, a level similar to that in TxT4.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2919602 TI - Removal of intracellular waste products by hemofiltration. AB - Because the total amount of waste products removed by hemofiltration can be measured exactly, it was divided into two components, that removed from the extracellular compartment and that removed from the intracellular compartment, using inulin as a marker for extracellular fluid in five uremic patients treated with hemofiltration in the postdilution mode. The amount removed from the extracellular compartment as a proportion to the total amount removed from the whole body by hemofiltration was 86.5% +/- 10.6% for guanidinosuccinic acid, 69.1% +/- 15.6% for sodium, 59.4% +/- 3.3% for uric acid, 56.4% +/- 2.1% for inorganic phosphate, 45.6% +/- 5.3% for creatinine, 43.1% +/- 7.2% for potassium, 42.9% +/- 3.1% for guanidinoacetic acid, 42.5% +/- 7.5% for methylguanidine, 37.2% +/- 8.4% for chloride, 36.3% +/- 2.8% for urea, and 6.9% +/- 2.9% for glucose. These results show that extracellular substances such as sodium and guanidinosuccinic acid were removed mainly from the extracellular compartment. On the other hand, glucose was removed only from the intracellular compartment, since blood glucose level is regulated. Although uric acid, inorganic phosphate, creatinine, potassium, guanidinoacetic acid, and methylguanidine are intracellular substances, they accumulated also in the extracellular fluid in renal failure, and were removed from both compartments, intracellular as well as extracellular, by hemofiltration. PMID- 2919603 TI - Effect of indomethacin on the glomerular filtration rate after a protein meal in humans. AB - The renal response to a protein meal has been characterized by increases in glomerular filtration rate (GFR) and renal plasma flow and decrease in renal vascular resistance. Several hormonal mediators of this response have been proposed, including renal prostaglandins (PGs). We studied ten normal subjects before and after ingestion of indomethacin. All subjects had three 30-minute baseline creatinine and iothalamate clearances measured before and three one-hour clearances measured after an 80-g protein meal. The night before the second test, the subjects took 25 mg indomethacin and 150 mg one hour before the test meal. Urine PG excretion decreased significantly during the second test, from 0.60 +/- 0.23 to 0.30 +/- 0.14 ng/min (P less than 0.01). Initial iothalamate clearance increased from 110 +/- 10 to a mean of 122 +/- 15 mL/min/1.73 m2 (average increase of 12 mL/min/1.73 m2) during the second hour after the test meal. After ingestion of indomethacin, the GFR remained unchanged from a baseline of 101 +/- 9 to 101 +/- 7 mL/min/1.73 m2 (average change of -1 mL/min/1.73 m2). Because the time of peak increase after the meal varied from subject to subject, the maximal increase in GFR after the meal was calculated and found to be significantly less during the second test, 13 +/- 3 v 22 +/- 4 mL/min/1.73 m2 (P less than 0.05). Because PGs can stimulate glucagon secretion and because glucagon has been suggested to mediate the protein-stimulate GFR response, we measured plasma glucagon during both tests; these levels were not different.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2919604 TI - Peritoneal mucormycosis in a patient receiving continuous ambulatory peritoneal dialysis. AB - A 48-year-old man receiving maintenance hemodialysis for 3 years and continuous ambulatory peritoneal dialysis for 1 year developed a clinical picture compatible with peritonitis. Three successive fluid cultures were negative, and only after filtration of a large volume of peritoneal fluid a fungus identified as a Rhizopus sp was isolated in cultures of the filtering devices. The same fungus was also isolated from the peritoneal catheter cuff. Intravenous amphotericin B was administered and both the abdominal and general conditions of the patient improved transiently. Twenty days after initiation of antifungal treatment, a clinical suspicion of intestinal perforation arose and an exploratory laparotomy was scheduled, but the patient died during the anesthetic induction. The patient never received deferoxamine; any conditions predisposing to mucormycosis, such as diabetes or immunosuppression, were also absent. PMID- 2919605 TI - Two case studies from a family with primary Fanconi syndrome. AB - We report two cases from a family with primary Fanconi syndrome. A 39-year-old white woman with a history of frequent bone fractures developed hypophosphatemia, hypouricemia, hypokalemia, metabolic acidosis, and renal glycosuria. Her 15-year old son had renal glycosuria without metabolic acidosis. Both had mildly to moderately impaired renal function. Determination of amino acids in 24-hour urine specimens confirmed the generalized nature of aminoaciduria. Acid-loading, bicarbonate-loading, and phosphate-loading tests revealed that the mother had proximal (type II) renal tubular acidosis and excessive renal loss of phosphate for her level of renal function. These tests for the son were normal or within normal limits of his renal function. Known causes of Fanconi syndrome, such as cystinosis and Wilson's disease, were excluded by slit-lamp eye examination and leukocyte cystine level determination. One unexpected finding in the son was the preseNce of nephrocalcinosis on x-rays; a percutaneous needle biopsy of the kidney showed tubular atrophy, interstitial fibrosis, and calcium oxalate crystal deposits. The two cases presented here represent a familial variety of the primary Fanconi syndrome, a rare entity with a limited number of cases reported in the literature. PMID- 2919606 TI - Glomerular crescents and pregnancy. PMID- 2919607 TI - Common symptoms in ambulatory care: incidence, evaluation, therapy, and outcome. AB - PURPOSE AND PATIENTS AND METHODS: Many symptoms in outpatient practice are poorly understood. To determine the incidence, diagnostic findings, and outcome of 14 common symptoms, we reviewed the records of 1,000 patients followed by house staff in an internal medicine clinic over a three-year period. The following data were abstracted for each symptom: patient characteristics, symptom duration, evaluation, suspected etiology of the symptom, treatment prescribed, and outcome of the symptom. Cost estimates for diagnostic evaluation were calculated by means of the schedule of prevailing rates for Texas employed by the Civilian Health and Medical Program of the Uniformed Services for physician reimbursement. RESULTS: A total of 567 new complaints of chest pain, fatigue, dizziness, headache, edema, back pain, dyspnea, insomnia, abdominal pain, numbness, impotence, weight loss, cough, and constipation were noted, with 38 percent of the patients reporting at least one symptom. Although diagnostic testing was performed in more than two thirds of the cases, an organic etiology was demonstrated in only 16 percent. The cost of discovering an organic diagnosis was high, particularly for certain symptoms, such as headache ($7,778) and back pain ($7,263). Treatment was provided for only 55 percent of the symptoms and was often ineffective. Where outcome was documented, 164 (53 percent) of 307 symptoms improved. Three favorable prognostic factors were an organic etiology (p = 0.006), a symptom duration of less than four months (p = 0.009), and a history of two or fewer symptoms (p = 0.001). CONCLUSION: The classification, evaluation, and management of common symptoms need to be refined. Diagnostic strategies emphasizing organic causes may be inadequate. PMID- 2919609 TI - Screening for hereditary non-polyposis colorectal cancer: a study of 22 kindreds in The Netherlands. AB - PURPOSE: Identification of the hereditary non-polyposis colorectal carcinoma syndrome (HNPCC) is a basis for secondary prevention. The objectives of this study are to investigate the natural history of HNPCC and to assess the effect of screening. PATIENTS AND METHODS: Screening for colorectal carcinoma was performed in 22 HNPCC families (colonoscopy or double-contrast barium enema and sigmoidoscopy). The patients were subdivided into two groups. Group A comprised patients with colorectal cancer who were referred because they were symptomatic. Group B included family members of these patients who were found to have a colorectal lesion by screening. We compared these groups with respect to the stage of tumor growth. RESULTS: Histologic examination of the tumors in Group A (87 patients) revealed Dukes A carcinomas in six patients, Dukes B carcinomas in 37, Dukes C carcinomas in 21, and Dukes D carcinomas in 10 patients (classification unknown in 13 patients). In Group B (20 patients), adenoma was found in 14 and carcinoma in six patients (Dukes A in two and Dukes B in four patients). A total of 93 patients, including those whose tumors were detected by screening, had a colorectal carcinoma. The age at diagnosis ranged from 24 to 81 years (mean age: 46 years). The location of the colonic tumors was proximal in 60 percent. Multiple primary tumors were found in 26 percent. CONCLUSION: These results suggest that screening leads to the early detection of colorectal carcinomas and adenomas in asymptomatic members of HNPCC families. Screening should be initiated at the age of 20 and continued during the life of the individual. Careful examination of the right colon is indicated because of the frequent occurrence of tumors in the proximal colon. A subtotal colectomy is indicated at the time of diagnosis of the initial colon cancer because of the risk of multiple primary tumors. PMID- 2919608 TI - Spectrum of dysautonomia in mitral valvular prolapse. AB - PURPOSE: Symptoms suggesting altered autonomic regulation of cardiovascular function have been noted in some patients with mitral valvular prolapse (MVP) but may also occur in patients with other disorders. We evaluated cardiovascular responses to autonomic stimuli in 118 patients with symptoms of dysautonomia, 78 of whom had MVP, and 40 of whom did not, to determine if unique patterns of these responses distinguished patients in one symptomatic subgroup from another. SUBJECTS AND METHODS: The responses of patients to standing, quantitated Valsalva maneuver, facial immersion in ice water, and administration of isoproterenol, phenylephrine, and tyramine were compared with those in 12 asymptomatic patients with MVP and 23 normal volunteers. RESULTS: Constitutional, cardiovascular, and neuropsychiatric symptoms occurred with similar frequency in the two symptomatic patient groups. The most common pattern of abnormal responses in symptomatic patients with or without MVP was (1) an increased heart rate and elevated plasma norepinephrine levels while supine and then while standing quietly for five minutes, (2) an exaggerated increase in heart rate during phase II of Valsalva, (3) a diminished bradycardic response during phase IV of Valsalva, and (4) an exaggerated heart rate response to administration of isoproterenol. The increased heart rate during Valsalva, but not the exaggerated sensitivity to isoproterenol, was correlated with the magnitude of the chronotropic response to standing only in symptomatic patients with MVP. Exaggerated hypertensive overshoot during phase IV of Valsalva was observed in only a few symptomatic patients. No consistent pattern of these abnormalities, however, was noted in any of the patient subgroups. Hemodynamic responses to autonomic stimuli in asymptomatic MVP patients were generally indistinguishable from those observed in normal subjects. CONCLUSION: These findings suggest that abnormal cardiovascular responses to autonomic stimuli may occur in any patient with symptoms of dysautonomia regardless of the presence or absence of MVP and that the pattern of these abnormal responses may be diverse. It is therefore important to characterize the pattern of altered autonomic regulation of cardiovascular function in each patient when considering mechanistic implications or making therapeutic decisions about these patients. PMID- 2919610 TI - Thyroid hormone resistance in a large kindred: physiologic, biochemical, pharmacologic, and neuropsychologic studies. AB - PURPOSE: Thyroid hormone resistance affects the pituitary gland and a variety of other tissues. We studied a large kindred with this disorder and measured a number of clinical markers of tissue metabolism to determine if these markers were useful in elucidating the sites and degree of resistance. PATIENTS: A kindred of 89 persons in four generations was identified; 44 had thyroid function tests, and 14 (five to 67 years old) were found to have thyroid hormone resistance. RESULTS: The inheritance pattern was autosomal dominant, with no common HLA haplotype. Physiologic measurements in five affected members showed marked heterogeneity. Four patients had normal baseline cardiac contractility, but only two experienced a shortening of their QKd interval into the hyperthyroid range with triiodothyronine (T3) therapy. Intrathyroidal 127I content was increased in two patients and was normal in two. Bone mineral content was normal in two men, but two women had marked osteopenia. The propositus, hypothyroid after inappropriate 131I therapy, had a hypothyroid ventilatory response to hypercapnea. This response became low normal during T3 (100 micrograms/day) administration but not during long-term thyroxine (T4) (300 micrograms/day) administration. Three other patients had values within normal limits and one had a hyperthyroid ventilatory response. Peripheral biochemical markers of thyroid hormone action were measured in 13 affected and 19 unaffected family members. Sex hormone-binding globulin was increased in zero of 13 affected patients (versus 19 of 20 hyperthyroid, chi 2:p less than 0.001); ferritin was elevated in two of 13 patients (versus 11 of 20 hyperthyroid, p less than 0.02); angiotensin converting enzyme activity was increased in one of 13 patients (versus 12 of 20 hyperthyroid, p less than 0.025). The eldest patient had marked cardiac sensitivity despite normal biochemical markers. We attempted to suppress the integrated thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH) using T3 (72 and 100 percent suppression in two patients), dopamine (40 percent suppression in one), 3,5,3'-triiodothyroacetic acid (TRIAC) (94 percent suppression in one), and verapamil (10 percent and 40 percent suppression in two). Neuropsychologic function was studied in 14 individuals (11 affected, three unaffected). Although mild impairments were detected, they were not specific for thyroid hormone resistance.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2919611 TI - Prevalence of granular lymphocyte proliferation in patients with rheumatoid arthritis and neutropenia. AB - PURPOSE: Granular lymphocyte proliferation and neutropenia with or without splenomegaly occurs with unknown frequency in rheumatoid arthritis. We decided to evaluate the prevalence of Felty's syndrome and granular lymphocyte proliferation among patients with rheumatoid arthritis and to determine the fraction of patients with granular lymphocyte proliferation who also had rheumatoid arthritis. PATIENTS, METHODS, AND RESULTS: We retrospectively analyzed 1,053 cases of rheumatoid arthritis and 13,505 marrow examination reports for the decade 1978 to 1987. Among patients with Felty's syndrome rheumatoid arthritis with neutropenia/leukopenia, and rheumatoid arthritis with splenomegaly, we identified 18 patients with neutropenia as a manifestation of rheumatoid arthritis. We also identified marrow examinations in 150 patients with rheumatoid arthritis. Using blood counts, microscopy of marrow, and surface antigen analysis of mononuclear cells, we determined that 12 patients had typical Felty's syndrome and six had granular lymphocyte proliferation, representing prevalences of 1.1 percent and 0.6 percent, respectively. No patient had granular lymphocyte proliferation without neutropenia. CONCLUSION: Granular lymphocyte proliferation and neutropenia with or without splenomegaly in rheumatoid arthritis commonly resembles typical Felty's syndrome. Further, the six patients with granular lymphocyte proliferation represent 20 percent of our institution's patients with granular lymphocyte proliferation, supporting the previously described common association of this disorder with rheumatoid arthritis. The relatively large fraction of deaths (due to malignancy and infection) among the patients with typical Felty's syndrome suggests that their mean survival may be comparatively less than in those with granular lymphocyte proliferation. PMID- 2919612 TI - Sleep apnea syndrome in chronic renal disease. AB - PURPOSE: We performed this study in order to expand on an earlier report indicating a high prevalence of the sleep apnea syndrome in male patients with end-stage renal disease treated with hemodialysis and to determine whether patients with chronic renal insufficiency (prior to the initiation of therapy for end-stage renal disease) and female patients with end-stage renal disease treated with hemodialysis were affected. PATIENTS AND METHODS: Polysomnography was performed in 26 male and female patients with chronic renal insufficiency and end stage renal disease treated with hemodialysis who were not receiving testosterone. They included 22 whose histories were suggestive of sleep apnea ("symptomatic") and four whose histories were not ("asymptomatic"). RESULTS: Sixteen of the symptomatic (73 percent) and none of the asymptomatic patients were found to have clinically significant sleep apnea syndrome (p less than 0.02). Both female patients and patients with chronic renal insufficiency had sleep apnea. In nine of these 16 cases, the disorder was primarily of the obstructive type. CONCLUSION: These preliminary data raise the possibility of an association of chronic renal disease and the sleep apnea syndrome, and suggest that some of the daytime sleepiness and disturbed nocturnal sleep in such patients may be related to sleep apnea. They also indicate that questioning patients with chronic renal disease and symptoms suggestive of a sleep disorder is useful in determining who are at high risk for the sleep apnea syndrome. Further study is required to establish a causal relationship between chronic renal disease and the sleep apnea syndrome, and to determine the prevalence of the latter in patients with end-stage renal disease. PMID- 2919613 TI - One particular leviathan. PMID- 2919614 TI - The prospects of autopsy: mortui vivos docuerunt? ("Have the dead taught the living?"). PMID- 2919616 TI - Hypercalcemia and renal insufficiency in a 56-year-old woman. PMID- 2919615 TI - Obtaining permission for an autopsy: its importance for patients and physicians. AB - This paper reviews the importance, benefits, and methods of increasing autopsy percentages. Its focus is on specific procedures for obtaining autopsy consent, particularly in terms of addressing the problems that most often interfere with obtaining permission for postmortem examination. Techniques for handling various misconceptions about autopsies are discussed. These guides for postmortem-related discussions with families will lead to improvement in overall physician performance and satisfaction. PMID- 2919617 TI - Hypersensitivity reaction to bacillus Calmette-Guerin treated with plasmapheresis. PMID- 2919618 TI - Superiority of magnetic resonance imaging over computer tomography for diagnosing isodense bilateral subdural hematomas. PMID- 2919619 TI - Primary amyloidosis with unusual bone involvement: reversibility with melphalan, prednisone, and colchicine. PMID- 2919620 TI - Human immunodeficiency virus type 1 in a seronegative patient with visceral Kaposi's sarcoma and hypogammaglobulinemia. PMID- 2919621 TI - Myelofibrosis and aplastic anemia: first report of the two disorders occurring sequentially in the same person. PMID- 2919622 TI - Fatal colchicine toxicity. PMID- 2919623 TI - Allopurinol hepatotoxicity. PMID- 2919624 TI - Intrathoracic extramedullary hematopoiesis simulating post-traumatic intrathoracic hemorrhage. PMID- 2919625 TI - Retinoid-associated hypertriglyceridemia in chronic granulomatous disease. PMID- 2919626 TI - Transient isolated thyrotropin deficiency in the postpartum period. PMID- 2919627 TI - A new roentgenographic sign: the split eggshell sign for aortic arch aneurysms. PMID- 2919628 TI - Hypercalcemia, primary hyperparathyroidism, and cardiac calcifications. PMID- 2919629 TI - Clinical significance of hyperbilirubinemia associated with Staphylococcus aureus septicemia. PMID- 2919630 TI - Serial studies of auditory neurotoxicity in patients receiving deferoxamine therapy. PMID- 2919632 TI - Subclinical hypothyroidism in the neonate: not to treat. PMID- 2919631 TI - Characterization of a new G6PD variant: G6PD Titusville. AB - We describe a new glucose-6-phosphate dehydrogenase mutant, G-6-PD Titusville. The propositus is a 7-month-old black male infant with a transient hemolytic episode. The mutant enzyme is characterized by abnormal electrophoretic mobility, thermolability, Km for NADP, abnormal deamino NADP use and a decreased sensitivity to inhibition by NADPH. G-6-PD activity of hemolysate, as measured under optimal in vitro conditions, was not initially decreased, whereas fibroblasts, granulocytes, and platelets showed a markedly decreased level of enzyme activity. These properties identify G6PD Titusville as a unique variant of this X-linked, housekeeping enzyme. We conclude that although the propositus with G6PD Titusville had a transient hemolytic episode, we cannot be certain whether this association was a causative one. PMID- 2919633 TI - Remission of chronic idiopathic myelofibrosis to busulphan treatment. PMID- 2919634 TI - Different vasomotor action of nifedipine on dynamic coronary obstructions and therapeutic response in effort and prinzmetal angina. AB - Variations induced by nifedipine (10 mg sublingually) in the residual lumen diameter of significant (greater than 50%) coronary lesions were assessed angiographically in 58 patients with effort angina (group 1) and in 19 patients with Prinzmetal angina (group 2). A relationship was sought between these acute variations of the stenotic lumen and the clinical response to treatment with the same drug (20 mg four times daily). Treatment efficacy was evaluated with exercise testing in group 1 and Holter monitoring in group 2. In group 1 the residual segment of stenotic diameter showed an increase, decrease, or no change with the calcium antagonist. Nifedipine failed to improve 40% of the cases (21% unchanged and 19% worsened) in group 1. In the same group of patients, the responses to exercise tests were dissociated from the acute vasomotor pattern. Changes in the pressure-rate product also did not explain the clinical results. In group 2 the majority of lesions had compliant portions, which invariably reacted to nifedipine with dilatation. All patients with the Prinzmetal form had relief of the anginal episodes with treatment. These data suggest that the therapeutic efficacy of nifedipine in classic effort angina probably is the net result of influences on the myocardial oxygen consumption and supply, and the acute coronary vasomotor pattern does not allow to predict the clinical response. Stenotic lesions in the Prinzmetal form possess a distinct sensitivity to the relaxant action of calcium channel blockade, which reasonably explains the highly positive response to treatment. PMID- 2919635 TI - Survival on dialysis therapy: one center's experience. AB - Patient survival while undergoing renal replacement therapy was evaluated from January 1, 1967, through June 15, 1986. There were 1,216 patients, of which 230 were treated by continuous ambulatory peritoneal dialysis (CAPD), 150 by home hemodialysis (HHD), and the remainder by dialysis in a free-standing dialysis facility (LCD). Covariate analysis found that patient survival on dialysis therapy was not influenced by race, sex, or marital status. Patients more than 60 years of age and patients with renal failure secondary to diabetes mellitus or hypertension had the worst survival on dialysis. Patients entering into CAPD were associated with diminished survival when compared to HHD but not to LCD. The ability of the initial dialysis technique to maintain a person on dialysis was not different when patients were matched for age, race, and etiology of renal failure. Only a randomized prospective trial will answer the question as to whether continuous ambulatory peritoneal dialysis can maintain a patient at home as long as home hemodialysis. PMID- 2919637 TI - Hospitals that succeed with nurses. PMID- 2919636 TI - Idiopathic pulmonary fibrosis: cellular and molecular pathogenesis. AB - Diffuse involvement of the pulmonary interstitium with abnormal fibrous tissue is a process that occurs in many settings. There are many possible etiologies for pulmonary fibrosis, but in the majority of individuals, a clear cause cannot be determined and a diagnosis of idiopathic pulmonary fibrosis (IPF) results. Despite limited knowledge concerning the etiology, recent advances in biomedical technology offer great promise for increasing our understanding of IPF. This review will focus on current concepts of the pathogenesis and therapy of IPF. PMID- 2919638 TI - Fighting over a critically ill patient. PMID- 2919639 TI - Cholesterol measurements--update. PMID- 2919640 TI - The White House nurses. PMID- 2919641 TI - How to fight MG fatigue. PMID- 2919642 TI - A mid-life crisis for baby-boomer nurses. PMID- 2919643 TI - Managing Myra's madness. PMID- 2919644 TI - Shared governance. Reality or sham? PMID- 2919645 TI - A career day--with a difference. PMID- 2919646 TI - Speaking out. More power to you. PMID- 2919647 TI - Commonsense tips for working with blind patients. PMID- 2919648 TI - An exercise program for dialysis patients. PMID- 2919649 TI - ECG rhythms made easier with algorithms. PMID- 2919650 TI - Midwest jobfocus. The midwest plains and simple. PMID- 2919651 TI - Why students choose ADN programs. PMID- 2919652 TI - Michigan jobfocus. Michigan's magic. PMID- 2919653 TI - She isn't what you see. PMID- 2919654 TI - Glucocorticoid receptor activation in isolated perfused rat hearts. AB - The formation of unactivated and activated glucocorticoid receptor complexes was studied in intact, isolated, perfused rat hearts in the presence of [3H]triamcinolone acetonide. Receptor activation, as quantified by the DNA cellulose-binding assay, began to increase within 30 s of perfusion and reached a final steady-state level (t 1/2 = 4.6 min) with 46% of the steroid-receptor complexes bound to DNA-cellulose. With the use of a linear potassium phosphate (KP) gradient (5-400 mM), unactivated receptors eluted from DEAE-cellulose anion exchange columns at approximately 250 mM KP. Two activated receptor forms appeared, which eluted either in the wash fraction (binder IB) or between 50 and 100 mM KP (binder II) and occurred with half times of 1.3 and 2.7 min, respectively. Postperfusion cytosol preparation did not markedly influence the results as receptor binding was reduced by 10% or less when a 100-fold excess of unlabeled triamcinolone acetonide was included in the homogenizing buffer. We conclude from these results that glucocorticoids are able to exert a direct effect on the heart through binding to their own receptor in the absence of endogenous hormones. The time dependency of receptor activation supports a physiological role for this process. However, activation rates, determined from conformational changes associated with altered DEAE-cellulose elution profiles and appearance of activated receptor forms, occur earlier and may not be coordinated with the rate of activation as quantified by DNA-cellulose binding. PMID- 2919655 TI - Regulation of intracellular calcium by cell pH in vascular smooth muscle cells. AB - Intracellular calcium (Cai2+) and intracellular pH (pHi) are important regulators of a variety of intracellular processes. Cai2+ is a regulator of muscle contraction, but the role of pHi is unclear. The purpose of this study was to determine the effect of alterations of pHi on Cai2+. A7r5 vascular smooth muscle cells (VSMC) were grown to confluence on glass cover slips. Cai2+ was determined with the fluorescent probe fura-2 and pHi with 2,7-bis-carboxyethyl-5(6)-carboxy fluorescein (BCECF). Alkalinization of the VSMC by exposure to 20 mM NH4Cl (delta pHi 0.41 +/- 0.07) resulted in a rise in Cai2+ from 99 +/- 8 to 146 +/- 13 nM (n = 5) in the presence of extracellular Ca2+ (Cao2+). In the absence of Cao2+, NH4Cl-induced alkalinization also resulted in a Cai2+ rise (delta Cai2+ = 26 +/- 4 nM, n = 5). Similar changes in Cai2+ were observed when cells were alkalinized by exposure to nigericin in a KCl buffer (pH 7.7). Neither 100 microM verapamil or 100 microM 8,8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate HCl (TMB-8) altered the alkaline-induced changes. After cellular Ca2+ stores were partially depleted by exposure to AVP in a Ca2+-free solution, subsequent cell alkalinization induced no changes in Cai2+. These results demonstrate that alkalinization of VSMCs leads to a rise in cytosolic Ca2+ via release of intracellular Ca2+ stores. The intracellular Ca2+ storage sites appear to be the same as those sites sensitive to AVP. Thus pHi may regulate Cai2+ and thereby play a role in the regulation of vascular smooth muscle tone. PMID- 2919656 TI - Regulatory volume decrease by cultured renal cells. AB - Volume regulatory responses of OK cells (a continuous epithelioid cell line from opossum kidney) are examined by electronic cell sizing and measurements of intracellular pH in cell suspensions. In response to a 40% reduction in osmolality, the cells swell and then subsequently shrink toward their starting volume. This regulatory volume decrease (RVD) is reduced by replacement of Cl- in the medium with acetate. Replacement of Cl- with NO3- accelerates the RVD. The RVD response is inhibited by 1 mM quinine or 100 microM 4,4' diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) in the medium. The inhibitory effect of 100 microM DIDS (but not 1 mM quinine) is altered by replacement of Cl- by NO3- in the medium. Hypotonic challenge does not induce a DIDS-sensitive net flux of acid-base equivalents. Addition of (9 microM) valinomycin also inhibits the RVD response. It is suggested that the RVD response of OK cells involves activation of separate K+ and Cl- channels. PMID- 2919657 TI - Stimulation of K-C1 cotransport in rat red cells by a hemolytic anemia-producing metabolite of dapsone. AB - Dapsone, a sulfone compound used in the treatment of leprosy and, more recently, Pneumocystis carinii pneumonia, produces as a major side effect a hemolytic anemia. This anemia is characterized by oxidation of hemoglobin to methemoglobin and increased splenic uptake of red blood cells. Using a rat model, Grossman and Jollow (J. Pharmacol. Exp. Ther. 244: 118-125, 1988) found that dapsone hydroxylamine (DDS-NOH), a dapsone metabolite, is responsible for its hemolytic effect in vivo. DDS-NOH also promotes hemoglobin binding to SH groups on rat red cell membrane proteins (Budinsky et al., FASEB J. 2: A801, 1988). Since the binding of hemoglobin and other reagents (e.g., N-ethylmaleimide) to membrane SH groups has been associated with increased K transport in red blood cells, we examined the effect of DDS-NOH on K efflux from rat red blood cells in vitro. Cells shrink when exposed to DDS-NOH (100 microM) in media with plasma-like ionic composition. This shrinkage is prevented if extracellular K is raised to 110 mM or if intra- and extracellular Cl are replaced by methylsulfate (MeSO4), suggesting involvement of a K-Cl cotransport pathway. Indeed, 100 microM DDS-NOH produces a 4- to 5-fold increase in K efflux in cells containing Cl but less than a 2-fold increase in cells containing MeSO4. This stimulatory effect is specific for K; Na efflux is slightly inhibited by 100 microM DDS-NOH. The concentrations of DDS-NOH required for half-maximal stimulation of Cl-dependent K efflux (53 microM) is similar to its half-maximal hemolytic concentration in rats (approximately 100 microM). Furthermore, the stimulation of Cl-dependent K efflux by DDS-NOH is greater than 80% reversed by subsequent treatment of the cells with dithiothreitol, suggesting involvement of SH groups. Our results indicate that DDS-NOH exposure stimulates an apparent K-Cl cotransport in rat red blood cells, resulting in cell shrinkage under physiological ionic conditions. Since shrinkage of red blood cells renders them less deformable (Mohandas et al., J. Clin. Invest. 66: 563-573, 1980), this suggests a pathophysiological mechanism whereby DDS-NOH exposure in vivo could promote increased splenic uptake of red blood cells and hemolytic anemia. PMID- 2919658 TI - Cross-bridge dephosphorylation and relaxation of vascular smooth muscle. AB - We tested the hypothesis that relaxation in vascular smooth muscle is the result of inactivation of myosin light chain kinase and cross-bridge dephosphorylation. Fast neurally mediated contractions of swine carotid medial strips were induced by electrical field stimulation. Termination of the stimulus resulted in relaxation with a half time of 2 min. Nifedipine (0.1 microM) increased the relaxation rate without significant effects on the contractile response. Cross bridge dephosphorylation was much faster than stress decay with basal levels reached within 1 min when 73% of the developed stress remained. The time-course data of dephosphorylation and stress were analyzed with a model that predicted the dependences of stress and isotonic shortening velocity on cross-bridge phosphorylation during contraction. Rate constants resolved from contraction data also fitted the relaxation data when the model's prediction was corrected for estimated errors in the phosphorylation measurements. Because Ca2+-dependent cross-bridge phosphorylation was the only postulated regulatory mechanism in the model, these results are consistent with the hypothesis that cross-bridge dephosphorylation is necessary and sufficient to explain relaxation in the swine carotid media. PMID- 2919659 TI - Acetylcholine-induced intracellular acidosis in rabbit salivary gland acinar cells. AB - Intracellular pH (pHi) was measured in acini isolated from rabbit mandibular salivary glands using the fluorescent pH-sensitive probe 2,7-bis(carboxyethyl) 5(6)-carboxyfluorescein (BCECF). Resting pHi was estimated to be 7.13 +/- 0.01 (mean +/- SE of 29 experiments). Stimulation with acetylcholine (ACh) caused an intracellular acidosis followed by a return of pHi toward the control value with a half time of approximately 3 min. The intracellular acidosis was dose dependent and could be abolished by pretreatment of the acini with atropine (10 microM), suggesting that it was due to a receptor-mediated event. Incubation of the acini in HCO3- -free solutions or treatment of the acini with the carbonic anhydrase inhibitor acetazolamide (1 mM) abolished the acidosis, suggesting that the acidosis might be caused by loss of HCO3- from the cell. The acidosis was not affected by either 1) pretreatment of the acini with the anion exchange inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), or 2) equilibration of the acini in Cl- -free solution (Cl- substituted with glucuronate). These results suggest that the postulated HCO3- efflux does not occur by Cl- -HCO3- exchange. However, Cl- -HCO3- exchange did appear to be present because replacement of Cl- caused a large DIDS-sensitive alkalinization of pHi, presumably caused by HCO3- uptake in exchange for Cl-. The recovery of pHi after the initial acidosis on stimulation with ACh could be blocked by 1 mM amiloride, suggesting that the recovery phase was mediated by Na+-H+ exchange. PMID- 2919660 TI - Effects of charge on membrane processing in the proximal nephron. AB - To examine the effects of molecular charge on membrane processing in renal tubular cells, the distribution of cationic and anionic ferritin was characterized in microperfused proximal nephron segments. During the first 7 min of proximal tubule perfusion, cationic ferritin was observed 1) bound to the brush-border membrane, 2) in apically positioned vesicles and vacuoles, 3) in lysosomes, 4) in vesicles adjacent to the basolateral plasmalemma, and 5) bound to the basolateral plasmalemma. Compared with anionic ferritin, the distribution of cationic ferritin was characterized by 1) a smaller relative grain density for lysosomes, 2) an accumulation of granules in an enlarged pool of apical cytoplasmic vesicles and vacuoles, and 3) a greater number of granules reaching the basolateral plasmalemma. During incubation directly in the presence of isolated renal cortical microvilli, binding of cationic ferritin increased significantly as pH was lowered from 8.0 to 4.5 and was greater than that of anionic ferritin, which varied little with pH. The data indicate that the molecular charge of endocytosed substances affects routing and membrane processing in proximal tubular cells, suggesting that their membrane-binding characteristics may influence transport patterns. PMID- 2919661 TI - Changes of tracheal smooth muscle stiffness during an isotonic contraction. AB - Stiffness of the series elastic component (SEC) of canine tracheal smooth muscle in isotonic contraction and relaxation was measured by applying small force perturbations to the muscle and measuring the resulting length perturbations. The quick, elastic length transient was taken as the change in length of the SEC (delta L). The force perturbation was a train of 10-Hz rectangular force waves varying from 0 to 10% maximum isometric tension (Po) in magnitude (delta P = 10% Po). Stiffness of the SEC was estimated by the ratio delta P/delta L. The change in SEC stiffness with respect to the change in muscle length was further studied by obtaining the stress-strain curves of the SEC at different muscle lengths using the load-clamping method. The clamps were applied at a fixed time (10 s after stimulation). Length of the muscle 10 s after contraction was controlled by the magnitude of the isotonic afterload. It was found that the apparent SEC stiffness increased as muscle length decreased. This stiffness increase is not likely due to an increase in the number of attached cross bridges, but it is probably due to the gradual diminution of the SEC length itself during muscle shortening. PMID- 2919662 TI - Detection of La3+ influx in ventricular cells by indo-1 fluorescence. AB - We exposed indo-1-loaded cultured embryonic chick ventricular cells to 0.03-1.0 mM extracellular lanthanum concentration ([La3+]o) and simultaneously measured cell contractile motion and the 410/480 nm fluorescence intensity ratio. After exposure to La3+, ventricular cells stopped contracting and relaxed within seconds, and the 410/480 fluorescence ratio increased. The increase in the 410/480 signal was related to [La3+]o but was not affected by short exposures to zero extracellular calcium concentration ([Ca2+]o) or caffeine, suggesting that the fluorescence was not caused by a La3+-induced increase in intracellular calcium concentration ([Ca2+]i) but rather to increased intracellular lanthanum concentration ([La3+]i). In vitro studies confirmed that indo-1 fluorescence was sensitive to La3+. The increase in [La3+]i in 0.1 mM [La3+]o was directly related to intracellular sodium concentration ([Na+]i), suggesting that La3+ entered cells via Na+-La3+ exchange. In contrast to ventricular cells, which have a functionally distinct Na+-Ca2+ exchange system, exposure of indo-1-loaded cultured bovine endothelial cells to La3+ failed to produce an increase in [La3+]i. These results indicate that exposure of ventricular cells to 0.1-1.0 mM [La3+]o results in a [La3+]i greater than 250 nM within 1 min. Therefore, changes in myocardial 45Ca2+ fluxes and contents induced by La3+ cannot be ascribed solely to extracellular La3+ effects. PMID- 2919663 TI - Ca-induced Ca release in malignant hyperthermia-susceptible pig skeletal muscle. AB - To provide information regarding the cause of the muscle rigidity in malignant hyperthermia-susceptible (MHS) pigs, the Ca-induced Ca-release mechanism of the sarcoplasmic reticulum (SR), the Ca uptake by the SR, and the Ca-activated tension production of the contractile system were examined in skinned skeletal muscle fibers from MHS and normal pigs. In muscles of MHS pigs, the rate of Ca induced Ca release was significantly higher than in normal muscle. The potentiation effect on Ca-induced Ca release by halothane and caffeine did not differ appreciably between MHS and normal fibers. The rate of Ca uptake by the SR and the Ca sensitivity of the contractile system of MHS fibers were not different from those of normal fibers, and halothane in an anesthetic concentration exerted no effect on them. Dantrolene inhibited the Ca-induced Ca release at 38 degrees C. These results suggest that the principal cause of malignant hyperthermia (MH) in MHS pigs is due to the enhancement of the Ca-induced Ca-release mechanism of the SR of the skeletal muscle. PMID- 2919664 TI - Inositol lipid turnover and compartmentation in canine trachealis smooth muscle. AB - We established conditions for the study of metabolism and compartmentation of inositol phospholipids in canine trachealis muscle. Unstimulated muscle was incubated with myo-[3H]inositol for 30 min at 37 degrees C which resulted in labeling of the tissue free myo-inositol pool, whereas only a small amount of radioactivity was incorporated into inositol phospholipids or inositol phosphates. After addition of 5.5 microM carbachol, phosphatidylinositol (PI), phosphatidylinositol-4-phosphate (PIP), and phosphatidylinositol-4,5-bisphosphate (PIP2), specific radioactivities increased exponentially, reaching apparent constant values in 180-240 min. Initial rates of increases in PI, PIP, and PIP2 specific radioactivities were 39, 32, and 66 times that measured in unstimulated muscle. Metabolic flux rates (nmol.100 nmol total lipid Pi-1.min-1) during development of force averaged 0.42 +/- 0.09 and during force maintenance averaged 0.14 +/- 0.01. Fractions of total PI, PIP, and PIP2 pools that were linked to muscarinic cholinergic activation were estimated to be 0.97, 0.85, and 0.65, respectively. Initial rates of increase in specific radioactivities and specific radioactivities during carbachol activation were similar in PI, PIP, and PIP2 fast active compartments, suggesting metabolic flux from PI to PIP to PIP2 was in near chemical equilibrium. Turnover times for PI, PIP, and PIP2 fast active compartments were estimated to be 21, 1.6, and 4.0 min, respectively. PMID- 2919665 TI - Na-Ca exchange in ferret red blood cells. AB - Ferrets have high Na (140 mmol/l) red blood cells. To determine whether ferret red cells had a Na-Ca exchange system, Na effluxes via the Na + K + 2Cl cotransrpoter and Ca effluxes via the Ca pump had to be inhibited. This was accomplished by replacing cell chloride with nitrate and by loading the cells with vanadate that inhibits the Ca pump. Under these conditions, extracellular Na (Naout) inhibited Ca influx. Intracellular Na (Nain) was required for the large Ca influx as replacement of Na with Li reduced Ca influx to less than one-tenth of the original rate. Caout stimulated Na efflux by about twofold. The Ca efflux from cells depleted of Na was increased from 0.8 to 3.2 mmol.l packed cells-1.h-1 by the presence of Naout. Cells placed in a Na-free solution accumulated Ca: total intracellular Ca was 20-fold higher than free Caout. Most of this Ca was released on addition of the Ca ionophore, A23187. Because the Na gradient had driven net Ca uphill, the fluxes of Na and Ca are coupled. In a Na-free solution, the K1/2 for Ca influx was usually approximately 10 microM (occasionally approximately 100 microM), and the maximal velocity (Vmax was 1.5-4.4 mmol.l packed cells-1.h-1. At Naout = 150 mM, K1/2 increased 5- to 150-fold. In some cells, Naout decreased Vmax by approximately fourfold, suggesting that Naout does not always compete with Caout.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2919666 TI - A simple device for rapidly exchanging solution surrounding a single cardiac cell. AB - This study describes the design and various physiological applications of a simple device to rapidly change the solution surrounding a single intact cardiac cell. It consists of a short length of double-barreled glass tubing (theta tubing) attached to a miniature solenoid. A cell is positioned in one of two parallel streams of solution that simultaneously flow from each barrel. Rapid solution switching is achieved by activation of the solenoid that directs the adjacent stream over the cell, changing the bulk solution within 7 ms. Approximately 150 ms were required to change the solution at the membrane surface of guinea pig ventricular cells, judging from potassium-induced changes in resting membrane potential. This delayed response was probably due to, in part, restricted diffusion in the transverse tubular system. The switching speed of this device makes it possible to change extracellular solutions during action potentials and voltage-clamp pulses. PMID- 2919667 TI - Physiological attributes of endogenous bioactive luteinizing hormone secretory bursts in man. AB - The exact nature of glandular secretory events is difficult to discern in vivo, since underlying patterns of hormone release are confounded by metabolic clearance. Moreover, conventional immunoassay does not always agree with bioassay. Here, we have used the rat interstitial cell testosterone in vitro bioassay of luteinizing hormone (LH) to measure serial LH concentrations in the normal adult human male. The resultant bioactive LH time series were analyzed by a deconvolution model in which circulating hormone concentrations are controlled by the operation of four finite, nonzero, and determinable parameters: 1) the location(s); 2) the amplitude(s), and 3) the half-duration(s) of underlying secretory bursts, acted on by 4) endogenous exponential clearance kinetics. A macroscopic secretory burst was modeled in the algebraic form of a Gaussian distribution of instantaneous molecular secretory rates. The physiological implications of this model were examined by analyzing bioactive LH pulsatility in eight men sampled every 10 min for 6 h. Multiple-parameter deconvolution disclosed endogenous bioactive LH half-lives of 53 +/- 5.4 min (range 38-76 min), in agreement with earlier independent estimates of 65 +/- 4.9 (42-87) min in four LH-deficient men given a 35 micrograms iv bolus of human LH. Calculated endogenous production rates of bioactive LH (0.48 +/- 0.06 mIU.min-1.ml-1) were also in accord with values estimated previously from steady-state infusions of LH. Deconvolution further indicated that underlying bioactive LH secretory bursts had half-durations of only 12.2 +/- 1.5 min, occurred at intervals of 56 +/- 1.3 min, and achieved amplitudes of 2.1 +/- 0.26 mIU.min-1.ml-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2919668 TI - Attenuation of the osmotic release of vasopressin by enkephalins in dogs. AB - To assess the possible role of circulating enkephalins in the osmotic release of vasopressin, Met5 (M-Enk)- or Leu5-enkephalin (L-Enk) dissolved in 0.9 or 10% NaCl was infused to either anesthetized or conscious dogs at a dose of 3.5 nM.kg 1.min-1 for 15 min. Intravenous infusion of M-Enk or L-Enk produced 150- to 200 fold increases in their plasma levels, and the elevated levels were maintained during the infusion. Although blood pressure (BP) in anesthetized dogs decreased significantly during L-Enk infusion, BP in conscious dogs was unaffected by both enkephalins. Neither M-Enk nor L-Enk infusion affected plasma vasopressin concentration (PAVP) in these anesthetized and conscious dogs that were not osmotically stimulated. PAVP in conscious time control dogs increased significantly after start of 10% NaCl infusion in spite of an increase in BP. M Enk or L-Enk significantly blunted the increase in PAVP induced by 10% NaCl infusion. This attenuation was not accompanied by any significant changes in plasma sodium concentration and BP compared with those of time control dogs. Thus increase in plasma enkephalins attenuates the osmotic release of vasopressin. PMID- 2919669 TI - Effect of hypercalcemia-producing tumor on 1,25(OH)2D3 biosynthesis in athymic mice. AB - Serum 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] levels are low in patients with malignancy-associated hypercalcemia (MAH), whereas murine models of MAH have high circulating 1,25(OH)2D3. To determine the effects of a hypercalcemia-producing tumor on circulating 1,25(OH)2D3, in vitro 25-hydroxyvitamin D1-hydroxylase (1OHase) activity was measured in kidneys from BALB/c athymic mice implanted with a hypercalcemia-producing human lung tumor. Twelve days of low-phosphorus diet (LPD) in control animals lowered serum phosphorus to levels found in tumor bearing mice fed normal phosphorus diet (NPD; 4.1 +/- 0.3 vs. 4.4 +/- 0.7 mg/dl, P = NS) and increased 1OHase activity (1.6 +/- 0.2 vs. 3.9 +/- 0.7 pmol.mg protein-1.5 min-1, NPD vs. LPD, P less than 0.05). 1OHase activity was greater in tumor-bearing animals fed NPD compared with control animals fed LPD (8.4 +/- 0.6 vs. 3.9 +/- 0.7 pmol.mg protein-1.5 min-1, P less than 0.01). High-phosphorus intake suppressed 1OHase activity in both control and tumor-bearing animals. Seven days of parathyroid hormone infusion in control animals fed NPD raised serum calcium (9.4 +/- 0.2 vs. 13.3 +/- 1.6 mg/dl, P less than 0.05) and suppressed 1OHase activity (0.25 +/- 0.02 vs. 0.02 +/- 0.002 pmol.mg protein-1.5 min-1, P less than 0.001). The inverse relationship of serum phosphorus and 1OHase activity was much steeper in the tumor-bearing animals, with greater enzyme activity at comparable levels of serum phosphorus. The present study indicates that 1) factors produced by the tumor stimulate 1OHase activity, and 2) hypophosphatemia is required for expression of enhanced enzyme activity. PMID- 2919670 TI - Palmitate oxidation by isolated working fetal and newborn pig hearts. AB - Palmitate oxidation and the effect of palmitate on glucose and lactate utilization were investigated in isolated, perfused, fetal (0.9 gestation), and neonatal (2 day old) pig hearts. Hearts were perfused under working conditions, developing a mean aortic pressure of 50-55 mmHg, paced at 180 beats/min for 30 min, with Krebs-Henseleit buffer containing 3% albumin, glucose (5 mM), and insulin (100 microU/ml). Palmitate (1 mM) and lactate (5 mM), either individually or in combination, were added to the perfusion buffer. Palmitate oxidation was assessed from 14CO2 production from [U-14C]-palmitate, glucose uptake as 3H2O production from D-[2-3H]-glucose, and lactate metabolism from changes in buffer lactate content. After perfusion, ATP, creatine phosphate, triglycerides, and glycogen were measured. Substantial palmitate oxidation was observed at both ages but was greater in neonatal hearts. Nevertheless, palmitate inhibited lactate utilization and glucose uptake similarly in fetal and neonatal hearts. Lactate also reduced palmitate uptake and oxidation by 40-60% in both fetal and neonatal hearts. During perfusions with palmitate, tissue concentrations of triglycerides increased approximately threefold in fetal hearts and were unaffected by lactate. Thus both palmitate and lactate can act as major energy substrates for the immature heart. Both substrates significantly (P less than 0.01) suppress glucose utilization, and each has suppressive effects on the other's metabolism. PMID- 2919671 TI - On the measurement of lactate turnover in humans. PMID- 2919673 TI - Regulation of intestinal biotin transport in the rat: effect of biotin deficiency and supplementation. AB - The effect of biotin deficiency and supplementation at pharmacological doses on the intestinal transport of the vitamin was examined in the rat using a brush border membrane vesicle (BBMV) technique. Transport of biotin in both jejunal and ileal BBMV was significantly (P less than 0.05-0.01) higher in biotin-deficient rats compared with control (pair-fed) rats. This increase in biotin transport appeared to be specific because transport of D-glucose was similar in the two rat groups. The increase in biotin transport in the deficient rats appeared to be mediated through a marked increase (146-230%) in the Vmax of the biotin transport process (with minimal change in the apparent Km), suggesting an increase in the number of the transport carriers. In contrast, supplementation at pharmacological doses of biotin caused significant (P less than 0.05-0.01) and specific decrease (suppression) in biotin transport compared with (unsupplemented) controls. The suppression of biotin transport in the supplemented rats appeared to be mediated through a marked decrease (58%) in the Vmax of the biotin transport process (with minimal change in the apparent Km), suggesting a decrease in the number of the transport carriers. These results provide evidence that biotin transport in the intestine is regulated by the level of the vitamin in the diet (and/or body stores). Furthermore, the results demonstrate the ability of the small intestine to adapt to the challenge of deficiency of an essential nutrient, a capability that may be crucial for the survival of the animal. PMID- 2919672 TI - Mechanisms contributing to gastric motility changes induced by PAF-acether and endotoxin in rats. AB - Platelet-activating factor (PAF) may be involved in the pathophysiology of gastrointestinal damage and motility changes. The effects of PAF in inducing gastric contractions in vivo have now been determined in pentobarbital sodium anesthetized rats. Local intra-arterial infusion of PAF (5-50 ng.kg-1.min-1 for 10 min) induced a maintained rise in intragastric pressure followed by a further postinfusion increase. Inhibitors of eicosanoid biosynthesis had no effect on these gastric motility changes. However, pretreatment with cimetidine or methysergide decreased by 50% the initial increase in intragastric pressure, whereas mepyramine, adrenergic alpha- and beta-receptor blockade, atropine, hexamethonium, or vagotomy had no effect. During the local infusion of tetrodotoxin, the initial increase in intragastric pressure was not maintained, and the postinfusion increase was abolished. With these inhibitors and antagonists, there was no consistent correlation between the extent of PAF induced mucosal damage and increase in intragastric pressure. Tetrodotoxin had no effect on the changes in intragastric pressure induced by the thromboxane mimetic U-46619. Administration of Escherichia coli and Salmonella typhosa endotoxin (50 mg/kg iv) also increased intragastric pressure, which peaked after 10 min and slowly declined thereafter. These effects were inhibited by the specific PAF receptor antagonist L652,731, suggesting that the endogenous release of PAF may contribute to the endotoxin-induced increases in gastric motility. The present study suggests that PAF initially acts directly on smooth muscle and through histamine and serotonin release with a secondary motility response due to activation of nonadrenergic noncholinergic, neuronal activity. PMID- 2919674 TI - Biliary obstruction dissipates bioelectric sinusoidal-canalicular barrier without altering taurocholate uptake. AB - To study immediate events during extrahepatic cholestasis, we investigated the effect of short-term biliary obstruction on the bioelectrical sinusoidal canalicular barrier in the rat using molecular weight-matched uncharged and negatively charged inert solute pairs. The bioelectrical barrier averaged -22 +/- 5 and -18 +/- 4 mV (NS) using the pair carboxy-/methoxyinulin and ferrocyanide/sucrose, respectively. After a 20-min biliary obstruction both decreased by 61 and 11%, respectively, but only the large molecular weight pair (the inulins) returned to base line after release of the obstruction. Inert solute clearances were increased after short biliary obstruction depending on molecular size and negative charge (ferrocyanide greater than sucrose greater than carboxyinulin greater than inulin), suggesting that both permeability and bioelectrical barriers were affected by obstruction. The hepatic extraction in vivo of a passively transported drug not excreted into bile (D-propranolol) was not affected by obstruction, whereas that of an actively transported drug (glycocholate) decreased from 66 +/- 8 to 41 +/- 20% during biliary obstruction (P less than 0.01). Unidirectional transfer of glycocholate was not affected by short-term biliary obstruction in the situ perfused rat liver; however, 2 min after [14C]glycocholate administration, increased return was observed in hepatic venous effluent in obstructed animals. Our findings demonstrate a loss of the bioelectrical barrier immediately after short-term biliary obstruction. Decreased hepatic extraction in the view of unaltered sinusoidal uptake demonstrates regurgitation of bile into blood during short-term biliary obstruction. PMID- 2919675 TI - Effect of Yersinia enterocolitica on intestinal mucin secretion. AB - Mucin and glycoprotein synthesis and secretion were evaluated in the upper, mid, and distal small intestine and in the proximal colon of rabbits infected with Yersinia enterocolitica (YE). Infected (INF) animals were examined on day 6 and compared with pair-fed controls and unmanipulated weight-matched rabbits. Tissue mucin content in vivo and mucin secretion in vitro, measured by a specific immunoassay, were significantly elevated in all four regions of the gut of INF rabbits compared with both control groups. In vitro secretion of stored glycoprotein, prelabeled with [3H]glucosamine, was not increased in the upper and mid small intestine of INF animals but was significantly elevated in the distal small intestine and proximal colon. In vitro incorporation of [14C]glucosamine was increased in all four regions of the gut of INF rabbits, but secretion of newly synthesized [14C]glycoprotein was only significantly elevated in the distal small intestine and proximal colon. A graded response was observed down the intestinal tract of INF rabbits, with the greatest increase in mucin content, synthesis and secretion occurring in the distal small intestine and proximal colon where the morphological impact of disease is also most severe. PMID- 2919676 TI - Bombesin ingestion stimulates epithelial digestive cell proliferation in suckling rats. AB - The characterization of a bombesin-like peptide in the breast milk of some mammals might suggest that this peptide may influence, in part, the postnatal development of the digestive tract. To test this hypothesis, our experiments investigated whether oral administration of bombesin affects epithelial progenitor cell proliferation in digestive organs of suckling and weaned rats. Four series of pups were given bombesin diluted in milk (20 micrograms/kg, 3 times daily) or milk alone, for 5 days during either the first, second, third, or fourth week of life. Pups were killed after [3H]thymidine pulse labeling. DNA labeling and mitotic indices were estimated in the oxyntic, antral, colonic mucosae, and exocrine pancreas. In all tissues examined, oral bombesin significantly increased over control values the two cell proliferative parameters studied during the suckling period (P less than 0.05 to P less than 0.001). In bombesin-treated rats, maximal stimulation of these parameters occurred in the second week of life. This effect of oral bombesin on the cell kinetics disappeared in all tissues after weaning. This study confirms the growth promoting effect of bombesin observed on the digestive system of the neonatal rat after subcutaneous administration of the peptide and shows that bombesin, when given orally to suckling rats, is sufficiently resistant to proteolysis to enable it to exert a stimulatory effect on digestive cell proliferation. However, our findings as such do not prove that milk bombesin-like peptide has a physiological influence on the developing gastrointestinal tract and pancreas. PMID- 2919677 TI - Intraenterocyte distribution of absorbed lipid and effects of phosphatidylcholine. AB - The present studies were designed to investigate the distribution of absorbed lipid in intestinal mucosal cells and to identify the chylomicron precursor pool. Rats were infused intraduodenally with glyceryl tri[9,10(n)-3H]oleate (135 mumol/h); other rats were in addition infused with 9 mumol/h of phosphatidylcholine. After 5-h infusion the proximal one-half of intestine was removed and the mucosa obtained. It was found that 50% of the radioactivity in the whole homogenate pelleted on centrifugation at 75,000 g.min. The supernatant was further fractionated by high-speed centrifugation resulting in a floating lipid layer, a supernatant, and a microsomal pellet. The results showed that these subcellular fractions had a triacylglycerol specific activity 46-52% of the infusate's specific activity. Including phosphatidylcholine in the duodenal lipid infusion increased the triacylglycerol specific activity of all subcellular fractions (70%) resulting in a specific activity approaching that of the infusate, which would be expected of chylomicron triacylglycerol. These studies demonstrate 1) that considerable mucosal lipid is distributed into a low-speed pellet, 2) that mucosal triacylglycerol specific activity can be greatly increased by including phosphatidylcholine in a lipid infusion, and 3) that despite obtaining multiple subcellular fractions, the chylomicron precursor pool could not be clearly identified in the mucosa of control rats. PMID- 2919678 TI - Autoregulation of muscarinic and gastrin receptors on gastric parietal cells. AB - In previous studies we demonstrated that parietal cell stimulation with gastrin and carbamoylcholine (carbachol) is accompanied by increased turnover of membrane inositol phospholipids. We conducted the present studies to examine whether membrane-associated protein kinase C activity is enhanced as a consequence of these events and to explore the role of this enzyme in regulating parietal cell function. We observed that carbachol and gastrin dose dependently increased membrane-associated protein kinase C activity while histamine did not. Furthermore, compounds such as phorbol esters and diacylglycerol, which are known to be direct stimulants of protein kinase C activity, also stimulated parietal cell aminopyrine uptake. In contrast, the phorbol ester 12-O-tetradecanoylphorbol 13-acetate and the synthetic diacylglycerol 1-oleoyl-2-acetyl-sn-glycerol inhibited both aminopyrine uptake and membrane inositol phospholipid turnover in parietal cells induced by carbachol and gastrin. The inhibitory effect appeared to result from reduction in the quantity of muscarinic and gastrin receptors without alterations in their specific affinities. These data suggest that protein kinase C mediates stimulation of parietal cells by gastrin and carbachol but also activates an autoregulatory mechanism via downregulation of muscarinic and gastrin receptors. PMID- 2919679 TI - Postprandial gastrointestinal blood flow and oxygen consumption during environmental cold stress. AB - We studied the independent and combined effects of feeding and environmental cold stress by measuring pre- and postprandial gastrointestinal blood flow (QGI), oxygen consumption (GIVO2), and oxygen extraction (GIO2ex) in seven awake 3- to 4 day-old piglets while in a thermoneutral environment (control phase, 31 degrees C) and during environmental cold stress (experimental phase, 20.5 degrees C). Each animal consecutively completed both the control and experimental phases. In the control phase, measurements were made before and 30 min after feeding. In the experimental phase, measurements were made before and 30 min after induction of cold stress. A feeding was then given and measurements repeated 30 min later during continued cold stress. QGI (ml.100 g-1.min-1) increased postprandially while in a thermoneutral environment (130 +/- 11 to 152 +/- 12) but not while in a cold environment (126 +/- 15 to 121 +/- 8). Postprandial GIVO2 (ml O2.100 g 1.min-1) increased from 2.1 +/- 0.2 to 3.7 +/- 0.5 while in a warm environment. During preprandial cold stress, an unexpected increase in GIVO2 was observed (1.7 +/- 0.2 to 3.1 +/- 0.5). Feeding while in a cold environment provoked a further significant increase in GIVO2 (3.1 +/- 0.5 to 4.2 +/- 0.4). All increases in GIVO2 were associated with increased GIO2ex. This study has demonstrated that 1) postprandial GIVO2 is appropriately increased during cold stress as a function of GIO2ex and 2) that fasting GIVO2 is increased during cold stress, demonstrating an intestinal metabolic contribution to cold-induced systemic thermogenesis. PMID- 2919680 TI - Stimulation of oxygen uptake by glucagon is oxygen dependent in perfused rat liver. AB - Livers from well-fed female Sprague-Dawley rats (100-150 g) were perfused at flow rates of 4 or 8 ml.g liver-1.min-1 to deliver O2 to the organ at various rates. During perfusion at normal flow rates (4 ml.g-1.min-1), glucagon (10 nM) increased O2 uptake in perfused liver by approximately 40 mumol.g-1.h-1. In contrast, glucagon increased O2 uptake by nearly 100 mumol.g-1.h-1 when livers were perfused at high flow rates. Increase in O2 uptake was directly proportional to flow rate and was blocked partially by infusion of phorbol myristate acetate (100 nM) before glucagon. Increase in O2 uptake due to elevated flow was not due to enhanced glucagon delivery, since infusion of 120 nM glucagon at normal flow rates only increased O2 uptake by approximately 40 mumol.g-1.h-1. On the other hand, when O2 tension in the perfusate was manipulated at normal flow rates, the stimulation of O2 uptake by glucagon increased proportional to the average O2 tension in the liver. Infusion of 8-bromo-adenosine 3',5'-cyclic monophosphate (BrcAMP; 25 microM) also increased O2 uptake more than twice as much at high compared with normal flow rates. In the presence of angiotensin II (5 nM), a hormone that increases intracellular calcium, glucagon increased O2 uptake by nearly 100 mumol.g-1.h-1 at normal flow rates. Infusion of glucagon or BrcAMP into livers perfused at normal flow rates increased state 3 rates of O2 uptake of subsequently isolated mitochondria significantly by approximately 25%. In contrast, perfusion with glucagon or BrcAMP at high flow rates increased mitochondrial respiration by 50-60%. Glucagon addition acutely to suspensions of mitochondria, however, had no effect on O2 uptake. These data are consistent with reports that glucagon administration in vivo or treatment of intact cells with glucagon increases O2 uptake of subsequently isolated mitochondria, a phenomenon that can account for the observed increase in O2 uptake in livers perfused at high flow rates with glucagon. Furthermore, these results are consistent with the hypothesis that the effect of glucagon on mitochondria is O2 dependent in the perfused liver. This is most likely due to an effect of intracellular calcium on a mechanism mediated via cAMP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2919681 TI - Ethanol stimulates leucine uptake by rat fetal hepatocytes via trans-stimulation. AB - Prior studies showed that exposure of cultured rat fetal hepatocytes to ethanol increased sodium-independent transport of alpha-amino-isobutyric acid and cycloleucine. Using leucine (Leu) as a probe, we now show that this is a reflection of trans-stimulation of system L inward flux. Transport of Leu was entirely sodium independent and beta-2-aminobicyclo(2,2,1)-heptane-2-carboxylic acid inhibitable. Uptake kinetics indicated two components, likely systems L1 and L2 reported for the adult hepatocyte. The low-affinity Km was in the 0.5 mM range, whereas the high-affinity Km was 2% of that value. Under optimal growth conditions, approximately 65% of the Leu was transported by the latter system. Strong bidirectional exchange was shown with Leu loading, stimulating initial Leu uptake by 66%. Externally directed transport was enhanced 2.9 times against 5 x 10(-3) M Leu vs. no external Leu. A 24-h exposure to ethanol (2 mg/ml) increased Leu uptake by up to 100%, an effect that could be mimicked by arrested cell replication. Both enhanced rates could be reversed by amino acid depletion, reflecting intracellular amino accrual that induced trans-stimulation of Leu uptake. Enhanced uptake was also reproduced in replicating cells by loading with increasing concentrations of Leu. PMID- 2919682 TI - Omeprazole and cimetidine versus pentagastrin in canine ex vivo gastric chamber. AB - The effects of acid inhibitory doses of omeprazole were compared with equieffective doses of cimetidine in the canine ex vivo stomach model (n = 30). Systemic blood pressure, temperature, stomach fluid and ion fluxes, potential difference, blood flow rates, and arterial and venous blood gases were monitored during each of nine 30-min periods. Two resting periods preceded seven periods of pentagastrin stimulation. During the last four of these, the drug effect was recorded (cimetidine 1.2 or 4.8 mumol.kg-1.h-1; omeprazole 0.3, 0.6, or 1.2 mumol/kg). Omeprazole (1.2 mumol/kg) produced 100% inhibition of stimulated acid efflux, no significant decrease in total gastric blood flow (venous outflow), 90% return of potential difference (PD) toward resting values, and a 55% reduction in stimulated oxygen consumption. Omeprazole also showed a dose-dependent K+ efflux at the two lower doses. Cimetidine (4.8 mumol.kg-1.h-1) given during pentagastrin stimulation showed a 70% decrease in total gastric blood flow, a 40% return of PD toward resting, and a 77% reduction in stimulated oxygen consumption. Neither drug showed significant changes in mucosal blood flow from resting values, thus supporting the principle that changes in gastric acid secretion and changes in blood flow are not necessarily correlated. PMID- 2919683 TI - Inhibition of gastric emptying by glucose depends on length of intestine exposed to nutrient. AB - Nutrients inhibit gastric emptying in a dose-related fashion. We postulated that load-dependent gastric emptying results from the saturation of mucosal absorptive mechanisms, so that a longer length of the small intestine is exposed to unabsorbed nutrients as more nutrient enters the intestine to participate in this negative feedback. To test this idea, we limited exposure of 0.25 to 1.0 M glucose meals to various lengths of duodenum and jejunum in 17 dogs. The effects of these limited perfusions were then compared with experiments in which the whole gut (ALL) was exposed to the nutrient. Maximal inhibition was seen with 1.0 M meal and was similar with perfusions of 150 cm and ALL. By contrast, even with the 1.0 M load, no inhibition of gastric emptying was seen when glucose meal was confined to the first 15 cm of the proximal duodenum. Only 50-60% of maximal inhibition was observed during confinement of 1.0 M meal to the proximal 65 cm. We concluded that glucose sensors are present in both the proximal and the distal gut and the inhibition was related to the length of the small intestine exposed to glucose. PMID- 2919684 TI - Quantitation of metabolites of isolated chicken enterocytes using NMR spectroscopy. AB - Isolated enterocytes prepared from chicken small intestine were studied by proton nuclear magnetic resonance (NMR). Perchloric acid extracts of cells were prepared from duodenum, jejunum, and ileum, and concentrations of 19 different metabolites were determined after the virtually complete assignment of all peaks in the aliphatic region of the spectrum. High concentrations of serine ethanolamine phosphodiester (SEP), creatine, taurine, and acidic amino acids were found in all segment extracts. Relatively high concentrations of SEP (approximately 12 mM) and acidic amino acids (approximately 3.5 mM) were found in the ileum, whereas creatine (3 mM) and lactate (6.5 mM) were found at higher concentrations in jejunum. Taurine (approximately 8 mM), choline (0.5 mM), and betaine (approximately 0.5 mM) were evenly distributed throughout the segments. Fasting (40 h) led to substantial increases in the concentrations of pyruvate, succinate, SEP, and taurine, while neutral hydrophobic amino acid concentrations fell appreciably. The significance of the findings is discussed, and the possible contributions of SEP, taurine, and choline to membrane lipid homeostasis are considered. PMID- 2919685 TI - New horizons for liaison psychiatry: biomedical technologies and human rights. PMID- 2919686 TI - The meaning of culturally sensitive research in mental health. AB - To answer the question of what culturally sensitive mental health research is, the author focuses on the entire process of research. He argues that research is made culturally sensitive through a continuing, incessant, and open-ended series of substantive and methodological insertions and adaptations designed to mesh the process of inquiry with the cultural characteristics of the group being studied. Illustrations include pretesting and planning of research, collection of data and translation of instruments, instrumentation of measures, and analysis and interpretation of data. The insertions and adaptations ideally have a cumulative effect in rendering individual projects culturally sensitive and in building culturally informed research. PMID- 2919687 TI - Legal principles in the psychiatric assessment of personal injury litigants. AB - The authors review the legal principles that a psychiatrist must understand in assessing the emotional and psychiatric sequelae of a personal injury leading to a litigation claim. The principles of the establishment of fault or liability, the assessment of pain and suffering, causal connection, the credibility of the plaintiff, the credibility of the expert witness, the determination of prognosis, the award of damages, and the adversarial system are discussed. An appreciation of these principles will enable psychiatrists to provide assessments that will be useful to the legal system in arriving at a fair and accurate determination of the compensation to which a victim is entitled. PMID- 2919688 TI - RDC alcoholism in patients with major affective syndromes: two-year course. AB - The authors examined the 2-year course of alcoholism as defined by Research Diagnostic Criteria (RDC) in 127 newly admitted patients with major affective syndromes and concurrent alcoholism at intake. The cumulative probability of remission (at least 6 months free of alcohol problems) in these patients was 0.67. Many of the remissions began within a few weeks of intake; the remaining were distributed over the follow-up period. Of the patients without remissions, 17% died, half by suicide. Diagnoses of schizoaffective disorder, indicators of alcohol dependence, and previous chronicity of alcohol problems predicted poor outcome of alcoholism, but none of these variables predicted subsequent relapse. PMID- 2919689 TI - Sleep EEG and DST findings in anergic bipolar depression. AB - The authors report sleep EEG and dexamethasone suppression test (DST) findings for a homogeneous sample of anergic bipolar depressed outpatients (bipolar I, N = 7; bipolar II, N = 19) characterized by motor retardation, volitional inhibition, hypersomnia, or weight gain and sleep EEG findings for 26 age- and sex-matched normal control subjects. Sleep architecture was abnormal in bipolar depression, particularly with respect to little stage 1 sleep. The biological profile of an anergic episode of bipolar depression did not include a shorter than normal mean REM latency, poor sleep continuity, or abnormally low amounts of stages 3 and 4 sleep, and only three (13%) of 23 patients manifested cortisol nonsuppression. PMID- 2919690 TI - Briquet's syndrome in association with depression and panic: a reconceptualization of Briquet's syndrome. AB - In a sample of 188 consecutive female psychiatric patients, Briquet's syndrome was found to be associated more closely with the aggregation of both major depression and either panic disorder or agoraphobia than with major depression or panic disorder-agoraphobia alone. These results are consistent with the hypothesis of a shared diathesis underlying some cases of major depression, panic disorder, agoraphobia, and Briquet's syndrome. The author proposes that Briquet's syndrome may represent the most extreme expression of a tendency for a number of physical and psychological syndromes to aggregate. PMID- 2919691 TI - Depression, hopelessness, and suicidal behavior in Chinese and American psychiatric patients. AB - The authors compared 37 patients in the People's Republic of China and 46 patients in the United States who were having difficulty with suicidal thinking or behavior. Hopelessness, reasons for living, and suicidal efficacy showed none of the expected relationships with suicidal intent among the Chinese patients, but the two groups were similar on many variables theoretically related to suicidality. Chinese patients were less likely to communicate suicidal intent and rated suicide as less effective at solving problems. The authors examine such variations in the light of possibly different cultural approaches to suicidal behavior. PMID- 2919692 TI - Depression and Alzheimer's disease. AB - In his classic case, Alzheimer described cognitive symptoms such as amnesia, aphasia, and apraxia and noncognitive symptoms such as delusions and agitation. Recent studies have suggested that depression also occurs in Alzheimer's disease. In this study, 144 patients who met criteria for Alzheimer's disease were examined for depression on a modified version of the Present State Examination. The prevalence rate of major depression was 17%. The depressed Alzheimer's disease patients were more cognitively impaired and more disabled than the nondepressed patients. Studies are needed to clarify the etiology and treatment of depression in Alzheimer's disease. PMID- 2919693 TI - Maintenance of an insanity defense under Montana's "abolition" of the insanity defense. AB - In 1979, Montana's insanity defense was replaced with the more restrictive mens rea defense, a change that has been described as an example of "abolition" of the insanity defense. The authors identified cases in which mental health was an issue in seven Montana counties for 3 years before and 3 years after the 1979 reform. They found that acquittals based on the insanity plea markedly declined, but that dismissals based on incompetence to stand trial increased substantially following the reform. They conclude that dismissal based on incompetence to stand trial became a substitute for acquittal based on the insanity plea under mens rea. PMID- 2919694 TI - Psychometric assessment of first-degree relatives of 62 autistic probands in Utah. AB - The Wechsler Intelligence Scales, Wide Range Achievement Test, and the Shipley Hartford Test were administered to 122 parents and 153 siblings of 62 autistic probands in Utah. Scores were distributed as expected within the published normative ranges for each scale. Parents' scores correlated with those of their nonautistic children, but neither parents' nor siblings' scores correlated with the IQ level of the autistic probands. These results do not confirm prior reports from England and the United States of a high rate of cognitive and learning problems in the siblings of autistic individuals, nor the aggregation of such problems in the siblings of probands with high or low levels of cognitive function. PMID- 2919695 TI - The psychiatric emergency service holding area: effect on utilization of inpatient resources. AB - This study compared the rates of hospitalization from two psychiatric emergency services which were similar except that one service had an extended evaluation unit, or holding area, allowing up to 24 hours of evaluation. The rate of hospitalization from the service with the extended evaluation unit was 36%; the rate from the other service was 52%. The difference in admission rates was related to the availability of the extended evaluation unit, which made it possible for many patients to avoid rather than merely postpone admission to the hospital. Clinical determinants of admission and of successful treatment in the unit were also reviewed. PMID- 2919696 TI - Adverse outcome of hip fractures in older schizophrenic patients. AB - The psychiatric and ambulatory course of 21 older chronic schizophrenic patients who sustained hip fractures was studied prospectively, and their walking ability after the fractures was compared to that of 25 nonpsychiatric hip fracture patients. Although the schizophrenic patients were younger when the hip fractures occurred, their recuperation and ambulatory outcome were significantly worse. The psychiatric course was assessed with a standardized rating scale that was administered 6 months and 1 year after the fractures and compared to similar ratings done before the fractures. Significant mental deterioration was found at 6 months after the fractures, with no further changes later. PMID- 2919697 TI - Self-reported anxiety in adolescents. AB - In a study of 988 adolescents, female gender, somatic complaints, history of physical and sexual abuse, poor grades, use of street drugs, and family history related to depression were among factors that differentiated adolescents reporting high anxiety from those reporting low anxiety. PMID- 2919698 TI - Carbamazepine-induced mania with hypersexuality in a 9-year-old boy. PMID- 2919699 TI - Seizure disorder misdiagnosed as borderline syndrome. PMID- 2919700 TI - What to do about extremely high plasma levels of tricyclics? PMID- 2919701 TI - Longitudinal assessment of older schizophrenic patients. PMID- 2919702 TI - Importance of the transference and therapeutic alliance in pharmacotherapy. PMID- 2919703 TI - Psychiatric aspects of lying. PMID- 2919704 TI - Polydipsia and hyponatremia. PMID- 2919705 TI - Controlling auditory hallucinations. PMID- 2919706 TI - Positive and negative syndromes in schizophrenia. PMID- 2919707 TI - Preference for alprazolam over diazepam. PMID- 2919708 TI - Suicide gestures and self-mutilation. PMID- 2919709 TI - Somatization in psychiatric patients. PMID- 2919710 TI - Diagnosis of refugees. PMID- 2919711 TI - Hemifacial flushing during unilateral ECT: an alternative explanation. PMID- 2919712 TI - The meaning of empathy. PMID- 2919713 TI - Ear wiggling tics. PMID- 2919714 TI - Dysthymia and depression. PMID- 2919715 TI - Issues in personality disorder diagnoses. PMID- 2919716 TI - Lymphadenopathy of Kimura's disease. AB - Kimura's disease is an important category of reactive lymphadenopathy in the Oriental population. The enlarged nodes are mostly located in the head and neck region. Salient pathological changes include florid germinal centers, Warthin Finkeldey type polykaryocytes, vascularization of germinal centers, increased postcapillary venules in the paracortex, eosinophilic infiltration, and sclerosis. The pathology of Kimura's disease is quite different from that of angiolymphoid hyperplasia with eosinophilia (epithelioid hemangioma). Immunoperoxidase studies show IgE reticular networks in germinal centers. Nondegranulated surface IgE-positive mast cells are present in the paracortex. The authors propose that Kimura's disease represents an aberrant immune reaction to an as yet unknown stimulus. Although the individual histological features are nonspecific, the constellation of features is highly characteristic of Kimura's disease. Since lymphadenopathy can herald involvement of other tissues and the prognosis is excellent, accurate diagnosis of this disease in lymph node biopsies may spare the patients unnecessary radical surgery. PMID- 2919717 TI - Infiltrating syringomatous adenoma of the nipple. A clinical and pathological study of 11 cases. AB - The clinical and pathologic findings of 11 infiltrating syringomatous adenomas of the nipple (ISA) were studied. All neoplasms were composed of small ducts and solid strands of epithelial cells surrounded by desmoplastic stroma. Ten of the 11 invaded the smooth muscle of the nipple, four extended to underlying breast tissue, and one showed perineural invasion. All lesions had an infiltrative margin, but 10 were treated successfully by local excision, even though five (45%) recurred. None metastasized. ISA must be distinguished from nipple duct adenoma and tubular carcinoma. Its clinical significance lies primarily in its recognition as a distinctive benign neoplasm. In the past, a variety of terms have been used to describe this lesion, whether it occurred in the skin, nipple, or substance of the breast. "Infiltrating syringomatous adenoma" is the preferred term to avoid using "carcinoma" for lesions involving the breast. PMID- 2919718 TI - Pathologic features of prognostic significance in adrenocortical carcinoma. AB - There are currently no well-established pathologic prognostic factors helpful in distinguishing low versus high grade adrenocortical carcinomas. The effect of 11 pathologic parameters on survival was investigated in 42 cases of adrenocortical carcinoma. Only one variable, mitotic rate, had a strong statistical association with patient outcome. The 21 patients with carcinomas with greater than 20 mitoses per 50 high power fields (hpf) had a median survival of 14 months, whereas the 21 patients with carcinomas with less than or equal to 20 mitoses had a median survival of 58 months (p less than 0.02). The presence of atypical mitoses, capsular invasion, tumor weight greater than 250 g, and size greater than 10 cm each showed a marginal statistical association with poor survival (p less than 0.06), whereas other features assessed, such as nuclear grade, presence of necrosis or of venous or sinusoidal invasion, character of the tumor cell cytoplasm, or architectural pattern, showed no statistical significance in predicting survival. It is proposed that adrenal cortical carcinomas with greater than 20 mitoses be designated high grade, whereas tumors with less than or equal to 20 mitoses be designated low grade. PMID- 2919719 TI - Vascular invasion in malignant melanomas. An independent prognostic variable? AB - The role of vascular invasion as a prognostic indicator in melanoma has not been fully evaluated, mainly due to difficulty in differentiating between capillaries and artefactual spaces caused by shrinkage in routine histological sections. However, immunohistochemical staining using Ulex europaeus I (UEA-I) permits accurate identification of tumor capillaries, thus facilitating recognition of vascular invasion. Sixty-six primary cutaneous melanomas were included in this study. Sections of each case were stained with UEA-I; then, vascular invasion at the level of the tumor capillary bed was sought. Hematoxylin-and-eosin-stained sections were reviewed; the thickness of each lesion was measured and the level of invasion and the growth phase of the tumors were also assessed. The frequency of vascular invasion was found to increase with increasing tumor thickness and with increasing level of invasion. Vascular invasion was seen in only one of 29 horizontal growth phase melanomas, whereas it was identified in 28 of 37 vertical growth phase tumors. Although these results would seem to indicate that vascular invasion within melanomas is unlikely to be an independent prognostic variable, they may partly explain the deteriorating prognosis associated with increasing tumor thickness. They also lend support to the concept of "horizontal" and "vertical" growth phase in melanoma. PMID- 2919720 TI - Renal parenchymal malakoplakia. Histologic spectrum and its relationship to megalocytic interstitial nephritis and xanthogranulomatous pyelonephritis. AB - We report five cases of renal parenchymal malakoplakia. They represent a histologic spectrum of this uncommon inflammatory process as it involves the renal parenchyma. Only one of these five cases presented the classical histologic picture of malakoplakia ("diagnostic stage"). Two cases--although with similar cellular infiltrate--had a marked paucity of Michaelis-Gutmann bodies and thus might have been classified as megalocytic interstitial nephritis were it not for the identification of such calcific intracellular inclusions under the electron microscope. The fourth case presented a pseudosarcomatous morphology and is similar to what has been described as a late or fibrous stage in malakoplakia of the urinary bladder. The last case had a destructive, frankly granulomatous histologic picture with a preponderance of foamy histiocytes reminiscent of xanthogranulomatous pyelonephritis, but with clusters of von Kossa-positive Michaelis-Gutmann bodies. The last two forms of the disease have not been previously reported to occur in the kidney. We believe that these cases represent various stages of development of the disease. PMID- 2919721 TI - Intraoperative pathologic consultation. An audit of 1,000 recent consecutive cases. AB - In order to assess the accuracy of the intraoperative consultation, or "frozen section," a retrospective review of 1,000 consecutive intraoperative consultations was performed. We present these data as a quality assurance assessment and as an update to a body of older literature examining the accuracy of the frozen section. The indications for intraoperative consultation and types of specimen submitted have changed in recent years, and these changes are related to the results in the present study. The increasingly important role of intraoperative cytology as an adjunct to and, in many cases, a replacement for frozen section is also emphasized. PMID- 2919722 TI - Stamping method for frozen section. AB - An easy and very quick method for proper orientation of tissue for frozen section is described. In this technique the stickiness of the cold chuck is used to advantage and the resulting slides are of improved quality. PMID- 2919723 TI - Localization of circumsporozoite antigen in exoerythrocytic schizonts of Plasmodium cynomolgi. AB - We used colloidal gold probes and post-embedding immunoelectron microscopy to localize circumsporozoite (CS) antigen in 5- and 8-day-old in vitro cultures of Plasmodium cynomolgi exoerythrocytic (EE) schizonts. Both small uninucleated and large multinucleated EE schizonts were found in 5-day-old cultures. A mouse monoclonal antibody to the repeat region of the P. cynomolgi CS protein densely labeled the plasma membrane and surface of 5-day-old EE schizonts as well as the surrounding parasitophorous vacuole membrane and space. Density of labeling decreased significantly as EE schizonts increased in size and maturity. Labeling of large, multinucleated 5-day-old schizonts was sparse and limited to the surface of EE schizonts and to small patches of electron dense material which were attached to the inner surface of the parasitophorous vacuole membrane. Mature 8-day-old EE schizonts with developing merozoites had little detectable labeling. CS antigen was not associated with internal structures within developing schizonts. Labeling was not observed in the host cell cytoplasm or on the surface of infected hepatocytes. These findings indicate that epitopes associated with the repeat region of the P. cynomolgi circumsporozoite protein are sequestered within infected host cells during EE development. PMID- 2919724 TI - The role of phospholipase in host cell penetration by Toxoplasma gondii. AB - Phospholipase A2 (PLA2) plays an important pathogenic role in infections caused by several microorganisms and has been implicated in host cell invasion. The mechanism of host cell penetration by the intracellular protozoan Toxoplasma gondii involves several steps; we have investigated the role of PLA2 in cellular invasion by the tachyzoite stage of this parasite. We assayed T. gondii invasion of human fibroblast monolayers by measurement of the selective incorporation of 3H-uracil into growing intracellular parasites. Exogenous PLA2 from snake venom (Naja naja) increased the penetration of fibroblasts by T. gondii, while horse antiserum to Naja hannah venom inhibited penetration. An irreversible PLA2 inhibitor, p-bromophenacyl bromide, blocked penetration without metabolically disabling the parasite. When host fibroblasts were preincubated with this drug, penetration was not affected, supporting a role for parasite rather than host cell PLA2 in the penetration process. Another PLA2 inhibitor, nordihydroguaiaretic acid, also inhibited penetration. We assayed extracellular T. gondii tachyzoites, purified from host cell debris, for PLA2 activity by radiometric detection of fatty acid release from labeled Escherichia coli membranes. Sonically disrupted parasites contained a low level of calcium dependent PLA2 with maximum activity at pH 8.5-9.0. These experiments suggest that a phospholipase is implicated in T. gondii host cell invasion. PMID- 2919725 TI - Kala azar with disseminated dermal leishmaniasis. AB - In this report we summarize 5 cases of kala azar with disseminated dermal leishmaniasis. All had fever, hepatosplenomegaly, and disseminated skin lesions on admission. Maculopapular, pustular, and maculonodular eruptions were present, located mainly on the face and extremities. Innumerable amastigotes were demonstrated in the bone marrow and in the skin biopsies. All patients responded to Glucantime therapy. PMID- 2919726 TI - Identification, using isoenzyme electrophoresis and monoclonal antibodies, of Leishmania isolated from humans and wild animals of Ecuador. AB - Six strains of Leishmania isolated from wild mammals and humans on the Pacific Coast of Ecuador were identified by isoenzyme electrophoresis and by their reactivity patterns to a cross-panel of specific monoclonal antibodies using a radioimmune binding assay. Single isolates from Sciurus vulgaris, Potos flavus, and Tamandua tetradactyla were identified as Leishmania amazonensis. Three other strains, isolated from cutaneous lesions of humans, were identified as Leishmania panamensis. PMID- 2919727 TI - Intestinal capillariasis in Egypt: a case report. AB - Capillaria philippinensis eggs, larvae, and adults were identified in the stool of a 41-year-old female physician from Cairo, Egypt, who had never traveled abroad. She had eaten local and imported fish. She suffered from borborygmi, abdominal pain, severe diarrhea, vomiting, and loss of weight for greater than 3 months. Treatment with Flubendazole (R17889-Janssen) 200 mg twice daily for 30 days resulted in clinical and parasitological cure. PMID- 2919729 TI - Cognitive nonsense. PMID- 2919728 TI - Epidemiology of hepatitis B in the Gezira region of Sudan. AB - To determine the prevalence of and risk factors for hepatitis B infection in rural Sudan, 2 villages in the Gezira were surveyed. There were 851 subjects (age 1-89 years; mean age 24.6 years) of equal sex distribution, 408 from Khalawaat and 443 from Saleim. HBsAg was found in 18.7%, and seropositivity for any hepatitis marker (HBsAg, anti-HBs, or anti-HBc) was found in 63.9%. The prevalence of HBsAg was highest in subjects less than 5 years of age (32.3%). Seropositivity for any hepatitis marker increased from 48.4% in subjects less than 5 years to 88.5% in persons greater than or equal to 50 years of age. HBeAg was present in 70% of HBsAg-positive women of childbearing age. Residence in Khalawaat and parenteral therapy for malaria were found to be independent risk factors for HBsAg-positivity. Age, residence in Khalawaat, crowding, and having had a tattoo were predictive of seropositivity for any hepatitis marker. The reason for increased markers of hepatitis B in Khalawaat compared to Saleim was not apparent. PMID- 2919730 TI - The consequences of current constraints on surgical treatment of appendicitis. AB - In this study, we sought to identify changes in the picture of a selected surgical condition during an interval of time that has brought about radical departures from previously established policies and programs. As a direct consequence, the patients take a more circuitous route to the surgeon. A significant number of patients with acute appendicitis in 1986 (37 percent) and 1987 (29 percent) suffered a prolonged delay in hospitalization or surgical referral compared with patients in 1980. This delay was accompanied by a more advanced stage of disease that ultimately caused a markedly increased morbidity (13 percent in 1986 and 24 percent in 1987, compared with 5 percent in 1980) and subsequent extended length of stay. This deterioration in patient care and failure at cost containment had previously been examined for conditions that can be operated electively. This study documents that the constraints also affect the treatment of patients whose initial condition requires urgent operative treatment. With specific relation to patients with acute appendicitis, surgeons recognize the value of the negative appendectomy. It appears the so-called gatekeepers must find a way to accept a certain negative hospitalization to referral rate. If current constraints will not allow this, the policies and programs behind the constraints should be changed. PMID- 2919731 TI - Postoperative gastric atony after vagotomy for obstructing peptic ulcer. AB - From 1979 through 1984, truncal vagotomy and drainage were performed in 71 patients with symptomatic obstructing peptic ulcers, whereas proximal gastric vagotomy with or without drainage was performed in 30 patients. Seven patients (7 percent) developed prolonged early postoperative gastric atony. Six of the 71 patients (8 percent) who had truncal vagotomy had atony, whereas only 1 of the 30 patients (3 percent) with proximal gastric vagotomy had atony (p = 0.08). The atony resolved with medical management in all patients after a median of 23 days. At follow-up (median 3 years), 74 percent of patients with truncal vagotomy had an excellent or good result compared with 86 percent of those with proximal gastric vagotomy (p greater than 0.1). The conclusion was that prolonged early postoperative gastric atony occurs uncommonly after vagotomy for obstructing peptic ulcer. Preservation of antropyloric innervation by using proximal gastric vagotomy instead of truncal vagotomy may be helpful, but does not completely prevent the atony. PMID- 2919732 TI - Gastric emptying and bezoars. AB - Bezoars are conglomerates of undigested material in the stomach, which appear as a late complication of gastric surgery and are presumably related to secondary motility changes. We studied the gastric emptying of a technetium-99m-(Tc 99m) labelled solid meal in 10 patients who presented with a bezoar 1 to 20 years after vagotomy and pyloroplasty, vagotomy and antrectomy, vagotomy and gastrojejunostomy, or hemigastrectomy. The results were compared with the emptying data of operated patients without bezoars. The gastric retention of Tc 99m-labelled solids at 45, 75, and 105 minutes was 85 +/- 15 percent (mean +/- SD), 79 +/- 17 percent, and 65 +/- 24 percent, respectively. No differences were found when results were compared with those of operated patients without bezoars. We concluded that factors other than the gastric digestive phase are the main contributors to bezoar formation. PMID- 2919733 TI - Ranitidine for prevention of postoperative suppression of delayed hypersensitivity. AB - Cell-mediated immunity was assessed by skin testing with seven delayed-type common antigens in 20 patients undergoing major abdominal surgery and in 20 nonoperative control subjects. The 20 surgical patients were randomized to perioperative ranitidine (50 mg every 6 hours for 72 hours) or no ranitidine. The 20 control subjects received either no ranitidine or ranitidine in the same dosage as the surgical patients. Skin tests were performed 2 days before and 1 day after operation with the same time schedule in the control subjects. Postoperatively, the diameter of the positive skin test area decreased in each of 10 patients without ranitidine (p less than 0.006) but increased in 9 and was unchanged in 1 of the ranitidine-treated patients (p less than 0.01). The skin test changes were similar during the two tests in ranitidine-treated surgical patients and the nonoperative control subjects. Ranitidine did not amplify the response in the nonoperated group. The potential role of histamine blockade in reversal of other aspects of postoperative immunosuppression and reduction in the risk of infection should be explored. PMID- 2919734 TI - Surgical morbidity in patients with systemic lupus erythematosus. AB - Thirty-six surgical procedures were performed on 29 patients with systemic lupus erythematosus (SLE). Nineteen cases involved active lupus at the time of surgery and 11 were performed on an emergent basis. Most patients had multiple organ involvement and were on some form of systemic therapy at the time of surgery. Thirty-seven postoperative complications were confined to 20 of these cases. Comparing this complicated group with the remaining 16 uncomplicated cases, the patients in the former group had a higher mean dose of steroid preoperatively, more organ involvement by SLE, and more frequent renal involvement; a higher percentage of the cases in this group were emergent rather than elective. The majority of factors examined failed to show predictive value in the outcome of surgery in lupus patients. We conclude that surgical complications are frequent in SLE patients and have identified four factors predictive of increased morbidity. PMID- 2919735 TI - Esophageal and jejunal motor function after total gastrectomy and Roux-Y esophagojejunostomy. AB - Emptying and peristaltic activity of the esophagus and proximal jejunum were studied using scintigraphy and fluoroscopy documented on videotape in 11 patients after total gastrectomy and Roux-Y loop reconstruction. Impaired esophageal motor function, as judged by both methods, was seen in five patients who were all 50 years of age or older. This was in contrast to the findings in a group of healthy control subjects, all over 50 years of age, in whom esophageal function appeared normal on scintigraphy in five of seven. Disturbed jejunal function, as judged by radiography, was found in eight patients, whereas the emptying rate according to scintigraphy was judged normal in all but two patients. Five of the patients complained of various adverse alimentary tract symptoms, but the scintigraphic and radiographic findings did not correlate with these symptoms. PMID- 2919736 TI - Is reperitonealization of the gallbladder bed a ritual or necessity? AB - Reperitonealization of the gallbladder bed after cholecystectomy is the standard procedure described in many textbooks of surgery. Most surgeons who advocate nondrainage after cholecystectomy also routinely obliterate the gallbladder bed. The theoretic considerations are a decrease in post-operative drainage and avoidance of adhesions to the liver. To evaluate the validity of the first consideration, 88 patients undergoing elective cholecystectomy were randomly allocated into two groups. In the first group, the gallbladder bed was reperitonealized whereas in the second group, the raw surface was left uncovered. No significant difference in the amount of postcholecystectomy drainage could be demonstrated in the two groups of patients studied. PMID- 2919737 TI - Pancreaticogastrostomy for chronic pancreatitis. AB - Forty-five patients with painful chronic pancreatitis underwent side-to-side pancreaticogastrostomy. Correct diagnosis was ensured by endoscopic retrograde cholangiopancreatography, decreased exocrine pancreatic secretion, abdominal calcifications, and histologic verification. A main etiologic factor was alcohol abuse (84 percent of patients). At a median follow-up period of 3.8 years, good, fair, and poor results were achieved in 56, 23, and 21 percent of patients, respectively. The operative mortality rate was 4.4 percent. At follow-up, 16 of the patients were employed, weight was increased by a mean of 2.5 kg, and the use of opiates was significantly reduced. Poor results were significantly related to preoperative use of tranquilizers and postoperative alcohol consumption. Neither patency of the anastomosis nor the time of observation were related to the operative result. The 8-year cumulative survival rate was 83 percent. PMID- 2919738 TI - Carotid eversion endarterectomy revisited. AB - Carotid eversion endarterectomy appears to be a safe and anatomically acceptable alternative to the standard carotid bifurcation endarterectomy, as evidenced by the absence of permanent neurologic morbidity and mortality in 98 operations. Preliminary clinical, angiographic, and noninvasive laboratory parameters suggest that there is a significant reduction of both residual technical defects and early recurrent stenosis. Specifically, no perioperative thrombosis or early restenosis was encountered in the 98 endarterectomies. Furthermore, only two technical defects have been noted, and one of these occurred in one patient who required a longitudinal arteriotomy and attendant suture line when the common carotid artery was transected too proximally and the eversion maneuver could not be accomplished. Serial long-term clinical and noninvasive laboratory follow-up evaluation, in addition to indicated postoperative angiography, will continue in an effort to assess the durability of a technical approach to carotid endarterectomy that may minimize residual defects and early restenosis. PMID- 2919739 TI - Comparison of regional and general anesthesia for carotid endarterectomy. AB - Two hundred twenty-one patients undergoing carotid endarterectomy were studied for morbidity and mortality. Thirty-seven had general anesthesia and 138 had regional anesthesia. The two groups were similar in preoperative risk factors and were operated on by a single surgeon and similar operative teams. Patient selection was prospective in the sense that the first 37 procedures were performed with general anesthesia and the next 184, with regional anesthesia. No significant difference in incidences of death, myocardial infarction, stroke, or transient ischemic attack was found. Hospital lengths of stay were similar. The type of anesthetic used for carotid endarterectomy should be the choice of the surgeon and operative team. PMID- 2919740 TI - An anatomic and functional classification for the diagnosis and treatment of inguinal hernia. AB - A simple classification of inguinal hernias is presented which can be valuable to surgeons as a (1) blueprint for dissecting the canal, (2) means for choosing the most appropriate operative procedure, (3) means for evaluating and correlating the prognosis of postoperative symptoms, time of convalescence, and degree of disability, and (4) method of identifying and communicating the exact anatomic derangement found so that accurate and consistent follow-up studies and statistics can be prepared. Diligent follow-up is essential for verifying the true results of hernia surgery techniques. Such follow-up requires that the surgeon be dedicated to examining his patients for many years, as well as to understanding, recording, and referencing the exact anatomic and functional defects found and the repairs used to correct them. Only with these factors identified and recorded can there be a basis for meaningful reporting and valuable conclusions. The classification of inguinal hernias presented here is intended to provide surgeons an opportunity to better evaluate their own methods and to more clearly communicate results with colleagues. As Oliver Wendell Holmes once said, "Many times ideas grow better when they are transplanted from one mind to another." PMID- 2919741 TI - Surgical needle sharpness. AB - We developed a standard reproducible test to determine surgical needle sharpness. This parameter was measured by recording the maximum force required to push a curved surgical needle through a thin laminated synthetic membrane. Three comparable groups of reversed cutting-edge needles were selected from different manufacturers for needle penetration testing. The results of this testing demonstrated that the needle diameter, manufacturing process, and the manufacturer were all important determinants of needle sharpness. Needles with a smaller diameter were sharper than those with a larger diameter. In addition, electrohoned or hand-honed needles were sharper than those subjected to only machine grinding. When comparably sized needles were compared, Ethicon manufactured the sharpest needles, followed by Davis & Geck and Deknatel needles. Scanning electron microscopic photographs and elemental analysis of the surgical needles could be correlated with their sharpness. The sharper needles had long, narrow cutting edge geometries compared with the short wide geometries of duller needles. The sharpest needles were fabricated from an American Society for Testing and Materials (ASTM) 45500 stainless steel alloy that has stronger tensile and yield strengths than those of ASTM 42000 and 42020 alloys used in the creation of the other needles. This stronger alloy allows the manufacturer to produce a longer, narrower cutting point geometry with reduced danger of either bending or breakage during surgery compared with needles made from weaker alloys (ASTM 42000 and ASTM 42020), which accounts for the superior sharpness of the Ethicon surgical needles. PMID- 2919742 TI - The suction knife in liver surgery. AB - A simple, inexpensive alternative method of blunt dissection for dividing liver parenchyma utilizing a suction knife is presented. The device, made from an ordinary suction tube, has been used successfully in six patients. Details of the device and method are discussed herein. PMID- 2919743 TI - Hepatic resection technique. AB - The author describes a technique of hepatic resection that is particularly beneficial for segmental and nonanatomic procedures. The technique is reportedly safe and accurate due to the use of the Nd:YAG laser and the ultrasonic dissector. PMID- 2919744 TI - Reliability of different grading systems used in evaluating surgical students. AB - Inter-rater agreement in assigning grades using five different grading systems was determined. The performance of 16 students in a surgery clerkship was rated by 21 faculty raters using a pass-fail grading system, a pass-fail-honors system, a letter grade system, a number grade scale from 1 to 10, and a number grade scale from 1 to 100. Inter-rater agreement coefficients were used to assess relative and absolute reliabilities, respectively. Both the letter grade and 1 to 10 number grade systems provided good discrimination, had high to moderate reliability, and required only five raters to achieve a mean rating with the commonly recommended reliability of 0.80. Using the letter grade system, however, a majority of raters agreed on a specific grade assignment for 14 of 16 students, in contrast to the 1 to 10 scale, for which this was true for only 4 of 16 students. The results of this reliability study favor the use of a letter grading system. PMID- 2919745 TI - Cisplatin in isolated limb perfusion. PMID- 2919746 TI - [The place of intra- and postoperative autotransfusion in the exchange of a hip endoprosthesis]. AB - Intraoperative autologous transfusion with a cell separator is being employed to an increasing extent in orthopedic procedures associated with high blood loss, including surgery for exchange total hip arthroplasty. Postoperative loss of blood via drains after exchange total hip replacement is also considerable. To our knowledge, there are only unpublished reports on postoperative autotransfusion in this type of surgery. In this study the role of intra- and postoperative autotransfusion is investigated. PMID- 2919747 TI - [Evoked potentials in the follow-up and prognosis of patients with craniocerebral trauma]. AB - The aims of this study were to find a reliable way of establishing the prognosis for the final outcome in the first week after head injury, to show the correlation between abnormalities in evoked potentials (EP) and clinical coma score, and finally, to document EP results in patients with the clinical diagnosis of brain death. We examined 46 patients, 23 in different states of coma and 23 with bulbar syndrome (complete absence of cortical and brain stem function). In the group of comatose patients brain stem auditory EP (BAEP) and somatosensory EP (SEP) were recorded in the first 48 h, 3-5 days, 1 week and 4 weeks after the head injury. The depth of coma was scaled with a scoring system devised by the authors and with the Innsbruck coma scale. Outcome was evaluated with the Glasgow outcome scale after 3, 6, and 9 months. BAEP were recorded bilaterally after stimulation with clicks; SEP were recorded from the neck (C2) and the contralateral cortex (C3', C4') after electrical stimulation of the median nerve. Evoked potentials were scored according to a four-point scale from grade 1 (normal) to grade 4 (only component I present in BAEP or absence of cortical responses on both sides in SEP). We found a significant correlation between the mean SEP score of the first week and the Glasgow outcome of the 3rd month, but no significant correlation between the BAEP score of the first week and the Glasgow outcome. There was a significant correlation between SEP (BAEP) scores and the corresponding clinical score.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2919748 TI - [Permeability of the alveolocapillary membrane during unilateral lung lavage. An experimental study]. AB - Experimental unilateral continuous lung lavage in a nonregenerating system containing 3000 ml isotonic crystalloid was performed in 12 pigs to determine the permeability of the alveolocapillary membrane under these conditions. The maximum time of lavage was 270 min. The concentrations of ions in both serum and fluid were determined at defined intervals. Exponential functions adjusted to the electrolyte changes in the fluid suggest different types of kinetics: sodium and urea adapted rapidly to serum concentrations. The half-time of the exponential function was short, the permeability constant high. Calcium, phosphate, and creatinine increased significantly, the permeability constant being lower than for urea. Potassium showed a linear increase, possibly due to influx from intracellular compartments. Total protein and albumin increased only initially, levelling far below the serum values. The low permeability constants of protein and albumin indicate an almost total lack of permeation, the initial increase possibly being due to washout of the epithelial lining fluid compartment. There was only a minimal loss of lavage fluid into the organism. PMID- 2919749 TI - [A fatal paradoxical air embolism during a routine obstetric procedure (cervical cerclage)]. AB - A lethal paradoxical air embolism (PLE) occurred in a 21-year-old secundigravida during general anaesthesia for cervical cerclage on account of cervical insufficiency. The diagnosis of PLE was verified postmortem; we initially diagnosed venous air embolism intraoperatively because of typical symptoms (cyanosis, pulmonary dysfunction, and vascular obstruction) and aspiration of air from the subclavian catheter. We also suspected an arterial embolism due to prominent neurologic deficits. In spite of corrective positioning, controlled ventilation (CPPV and PEEP), volume therapy, and sympathomimetics, resuscitation remained unsuccessful. This very rare complication depends upon several conditions: (1) opened, non-collapsible veins; (2) a pressure gradient from outside to inside the veins; (3) a patent foramen ovale; and (4) a right atrial pressure greater than that on the left, which can cause an air embolism to either the coronary or cerebral circulations. The pathophysiology and causative factors are discussed extensively as the immediately started resuscitation could not alter the lethal course. PMID- 2919750 TI - [The HELLP syndrome--a rare form of preeclampsia. Anesthesiologic and obstetric aspects]. AB - A 34-year-old quadripara was hospitalized in the 33rd gestational week due to an acute hypertensive crisis, headache, upper abdominal pain, icterus, and proteinuria. Laboratory testing revealed hemolysis, hepatic dysfunction, and thrombopenia. The values returned toward normal after delivery by cesarean section. Diffuse bleeding in the surgical wound and acute renal failure necessitated two relaparotomies, intensive hemotherapy, and hemodialysis. Mother and child were released in good condition. Anesthesiological and obstetrical aspects of the HELLP syndrome are discussed. PMID- 2919751 TI - [Fibrinolytic treatment of superior vena cava syndrome, a complication of a central venous catheter]. AB - Central venous catheterization plays a major role in anesthesia and intensive care medicine. Catheter-induced thrombosis, a common complication, develops in 15 47% of cases. A possible sequela is the occlusion of a large central vein; one early sign is edema of the upper extremities or face. Although complete occlusion of a central vein appears to be rare, this complication should be recognized in view of the extensive use of central venous catheters today. We report a case of severe superior vena cava syndrome that developed after catheterization of the right internal jugular vein. Fibrinolytic treatment using streptokinase and urokinase proved to be successful. A dose of 100,000 units/h was chosen for each agent, and heparin was added during urokinase therapy. Profound clinical improvement was observed after a few hours. Bleeding complications did not occur during the 4 days of treatment. PMID- 2919752 TI - [Catheter induced rupture of a proximal pulmonary artery caused by vigorous coughing in a spontaneously breathing patient]. AB - A complication is occurred during insertion of a pulmonary artery catheter in a 73-year-old woman with class III NYHA cardiac failure. After easy insertion of the catheter, massive haemoptysis developed as the patient coughed while the balloon of the catheter was inflated. Despite prompt emergency measures, the patient did not survive. Autopsy revealed a 2.7-cm perforation of the proximal pulmonary artery with penetration into the right lower lobe bronchus. This complication and its prevention are discussed. PMID- 2919753 TI - [Is the infusion filter a hygienic necessity?]. PMID- 2919754 TI - Spinal analgesia with morphine and clonidine. PMID- 2919755 TI - Hepatotoxicity and metabolism of isoflurane in rats with cirrhosis. AB - A rat model was used to determine whether isoflurane exacerbates liver dysfunction and whether its metabolism is changed in the presence of cirrhosis. Male Wistar rats were gavaged weekly with carbon tetrachloride until cirrhosis was well advanced. They and control rats without pretreatment with carbon tetrachloride and without cirrhosis were then exposed to 1.45% (1 MAC) isoflurane for 3 hours. Blood and urine samples were taken before, immediately, as well as 4, 24, 48, and 72 hours after anesthesia to measure liver function and isoflurane defluorination. After the last samples had been obtained, the rats were sacrificed and the liver removed for histologic examination and in vitro metabolic studies. Serum levels of SGOT and SGPT and inorganic fluoride production in rats with cirrhosis were similar to those in control rats without cirrhosis. Concentrations of cytochromes b5 and p-450 and specific activities of microsomal defluorinase and several cytosolic enzymes were significantly lower in cirrhotic than in noncirrhotic liver, but their total amounts in whole liver were the same. The results imply that cirrhosis does not increase the risk of acute hepatotoxicity of isoflurane. They also demonstrate that metabolism of isoflurane and perhaps other volatile anesthetics may be unaffected in rats with cirrhosis, even though liver architecture is severely disrupted. PMID- 2919756 TI - Effects of halothane and enflurane on conduction velocity and maximum rate of rise of action potential upstroke in guinea pig papillary muscles. AB - Using standard microelectrode techniques, the effects of halothane and enflurane on the maximum rate of rise of action potential upstroke (Vmax) and conduction velocity of excitation were compared with those of fast sodium channel blockers in isolated guinea pig papillary muscles. Lidocaine and tetrodotoxin decreased the square of the conduction velocity in proportion to the decrease in Vmax. In contrast, halothane and enflurane only slightly affected Vmax, but decreased the conduction velocity in a concentration-dependent manner. These results suggest that these volatile anesthetics affect conduction velocity by a mechanism different from that of fast sodium channel blockers. Caution should be used when these anesthetics are administered to patients receiving class 1 antiarrhythmic agents or who have pre-existing intraventricular conduction disease. PMID- 2919757 TI - Status of the match in anesthesiology: 1988. AB - The majority of anesthesia program directors agreed 2 years ago to use the National Resident Matching Program (NRMP) as the mechanism for appointing senior medical students to second postgraduate year positions in anesthesiology. Eighty seven applicants for the Mayo Clinic program were surveyed to measure the level of cooperation with the NRMP by programs and applicants. Low percentages of applicants reported pressures to sign contracts (22.4%) or make verbal commitments before February (32.8%). The frequency of these incidents was extremely low when considered in light of the number of applicant interviews reported by the applicants who responded. Nonparticipation in the match is a more important problem than infractions of NRMP rules. PMID- 2919758 TI - A randomized comparison between midazolam and thiopental for elective cesarean section anesthesia. I. Mothers. AB - In a randomized blind trial midazolam (0.3 mg kg-1) was compared with thiopental (4 mg kg-1), both combined with meperidine-nitrous oxide, for elective cesarean section anesthesia in 40 women. We found no statistically significant differences between thiopental and midazolam at induction, during operation or recovery with regard to maintenance doses, change in maternal neurologic status based on a modified Glasgow Coma Scale, systolic blood pressure, and heart rate. Induction time was 120 seconds with midazolam and 111 seconds with thiopental. There were significant differences with regard to diastolic blood pressure. Side effects occurred with approximately equal frequencies, but vomiting was significantly more frequent after thiopental. Perivenous tenderness and erythema occurred in four patients, all after thiopental. Midazolam appears to be a suitable alternative to thiopental for the induction and maintenance of anesthesia for elective cesarean section. PMID- 2919759 TI - A randomized comparison between midazolam and thiopental for elective cesarean section anesthesia: II. Neonates. AB - In a randomized blind trial, the general condition of 40 neonates was assessed following midazolam- or thiopental-based general anesthesia for elective cesarean section. Among 19 neonatal neurobehavioral observations and tests, statistically significant differences between the midazolam and the thiopental groups were rare. However, a statistically significant interaction with regard to body temperature, general body tone, and arm recoil was observed where results were inferior for midazolam, although only within the first 2 hours. It was concluded that midazolam is as safe as thiopental for the induction and maintenance of elective cesarean section anesthesia in neonates. PMID- 2919760 TI - A randomized comparison between midazolam and thiopental for elective cesarean section anesthesia: III. Placental transfer and elimination in neonates. AB - Forty neonates delivered by cesarean section were studied, half being delivered of mothers in whom anesthesia was induced with midazolam (0.3 mg/kg intravenously) and half of mothers given thiopental (4 mg/kg). At delivery, blood samples from mother and the umbilical vein were drawn for determination of plasma concentrations of thiopental, midazolam, and alpha-hydroxymidazolam. Over the next 60 hours, three blood samples were drawn using a randomized procedure of two blood samples at 30 different times. Placental transfer, expressed as the umbilical/maternal concentration ratio, was 0.96, 0.66, and 0.28, respectively, for thiopental, midazolam, and alpha-hydroxymidazolam. The transfer of thiopental was significantly more rapid than the transfer of midazolam and alpha hydroxymidazolam. The population average of elimination half-life in neonates was 6.3 hours for midazolam and 14.7 hours for thiopental. Both values are substantially larger than those found in previous studies in adults. PMID- 2919761 TI - Extent of blockade with various approaches to the lumbar plexus. AB - The extent of blockade when four different techniques were used for blocking the lumbar plexus was prospectively evaluated in 80 adult patients. The extent of blockade was measured by testing motor function of all nerves except the lateral and posterior femoral cutaneous nerves, which were evaluated by pinprick response. The posterior approaches of Dekrey at L3 (n = 20) and Chayen at L4-5 (n = 20) proved similarly effective in producing blockade of the femoral, obturator, and lateral femoral cutaneous nerves, as well as the nerves to the psoas muscle. The anterior approach of Winnie (femoral sheath or 3-in-1 block) using paresthesia (n = 20) or peripheral nerve stimulation (n = 20) proved effective in producing blockade of the femoral and lateral femoral cutaneous nerves, but ineffective for obturator nerve blockade. None of the four techniques produced blockade of the sacral plexus. Perhaps our means of assessing blockade (motor) is what produced the difference between our findings and those of others. PMID- 2919762 TI - Comparison of sedative infusions during regional anesthesia--methohexital, etomidate, and midazolam. AB - Using a randomized, double-blind study design, the intra- and postoperative sedative effects of three intravenous central nervous system depressants were compared in 64 patients during regional anesthesia. After establishing regional anesthesia, methohexital 59 +/- 29 mg IV, etomidate 12.6 +/- 8 mg IV, or midazolam 3.7 +/- 1.5 mg IV (mean dose +/- SD) were infused in a titrated fashion over 5-15 minutes to achieve similar end points of sedation. This level of sedation was then maintained with a variable-rate infusion of either methohexital 180 +/- 65 mg/hr, etomidate 32 +/- 12 mg/hr, or midazolam 7.5 +/- 4 mg/hr (mean dose +/- SD) To maintain a stable level of sedation, changes in the maintenance infusion rate were required more frequently with methohexital (4.6 +/- 3 times) than with etomidate (2.6 +/- 2 times) or midazolam (2.7 +/- 3 times). Decreases in oxygen saturation below 95% were more frequent with midazolam than with methohexital and etomidate, while recall of intraoperative events was less frequent after midazolam. Observer evaluations found less sedation in the methohexital and etomidate groups than in the midazolam group during the early postoperative period. However, the patients' evaluation of residual sedative effects (e.g., postoperative sedation visual analogue scores) and discharge times from the recovery room were similar in all three groups. Nevertheless, patients given midazolam had significantly greater impairment of performance on the digit symbol substitution test in the early postoperative period than did patients given either methohexital or etomidate. PMID- 2919763 TI - Doxacurium chloride for neuromuscular blockade before tracheal intubation and surgery during nitrous oxide-oxygen-narcotic-enflurane anesthesia. AB - The neuromuscular effects of doxacurium (BW A938U) were studied in 36 patients, divided into four groups of 9 patients each, given doxacurium either 50 micrograms/kg (2 x ED95) 5 or 4 minutes or 80 micrograms/kg (3 x ED95) 4 or 3 minutes before tracheal intubation. Adequate neuromuscular relaxation permitted successful intubation at 5 minutes for doxacurium 50 micrograms/kg and at 4 minutes for 80 micrograms/kg. Time to 90% blockade was 5.4 +/- 1.5 minutes for doxacurium 50 micrograms/kg and 3.5 +/- 1.2 minutes for 80 micrograms/kg. Time to 25% spontaneous recovery was 84.7 +/- 54.3 minutes for doxacurium 50 micrograms/kg and 164.4 +/- 85.2 minutes for 80 micrograms/kg. Either neostigmine 45 micrograms/kg, neostigmine 60 micrograms/kg, or edrophonium 1000 micrograms/kg was given for reversal when T1 had spontaneously recovered to 25% of baseline level, T1 being the first response to repetitive train-of-four (TOF) stimuli (2 Hz for 2 seconds at 10-second intervals) expressed as percent of baseline level. The T4:T1 ratio is the amplitude of the fourth twitch relative to the first twitch in a TOF stimulus expressed as a ratio. T1 rapidly achieved 90% of baseline in 5-10 minutes after reversal of neuromuscular blockade. In contrast, the T4:T1 ratio lagged, recovering to a mean of 0.6 at 20 minutes when T1 was over 90% of baseline. Recovery patterns were not statistically significantly different (unpaired t-test) among the three reversal regimens. Therefore, the reversal data were pooled. No clinically significant hemodynamic effects occurred in any group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2919764 TI - Influence of nifedipine on systemic and regional hemodynamics during adenosine induced hypotension in dogs. AB - Previous pharmacologic studies indicating competitive interactions between adenosine and nifedipine at the adenosine vascular receptor suggest that adenosine may be a less effective hypotensive drug after pretreatment with nifedipine. This hypothesis was tested in 18 pentobarbital-anesthetized, open chest dogs by evaluating the hypotensive effects and regional hemodynamic responses to 60-minute intravenous adenosine infusions before and after bolus injection of nifedipine (20 micrograms/kg, IV). Regional blood flow was measured with 15-microns radioactive microspheres. Before nifedipine, infusion of adenosine at a rate of 126 +/- 30 mumol/min caused a 50% reduction in mean aortic pressure that in the presence of no change in aortic blood flow was attributable to a proportional decrease in systemic vascular resistance. These systemic effects were associated with heterogeneous changes in regional blood flow; blood flow decreased in the renal cortex (-68%), pancreas (-50%), spleen (-77%), and skin (-61%); increased in the left (+112%) and right (+265%) ventricular myocardium; and did not change significantly in the duodenum, liver, skeletal muscle, or brain. Nifedipine did not alter the dose requirement or time course of the adenosine-induced hypotensive response or affect the associated systemic hemodynamic changes. Furthermore, nifedipine caused only minor alterations in the regional blood flow changes during adenosine-induced hypotension. Apparently the high plasma levels of adenosine required for controlled hypotension in the present study were sufficient to overcome the blocking influence of nifedipine at the adenosine vascular receptor. The study demonstrates that the hypotensive action of adenosine remains unimpaired after pretreatment with nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2919765 TI - Anesthesia for cesarean section--effects on neonates. AB - The effects of general and regional anesthesia on neonates after cesarean section have been studied mainly on elective cases. In this paper we studied infants delivered by elective and nonelective cesarean section at the Winnipeg Women's Hospital from 1975 to 1983 (n = 3940) to determine the effect of anesthetic technique on neonatal outcomes. A trained anesthesia nurse interviewed all parturients and reviewed their antepartum, labor and delivery, and anesthesia records. Assessments of neonatal outcomes were based on 1- and 5-minute Apgar scores, need for positive pressure oxygen by mask or intubation, and neonatal deaths (within 30 days). These outcomes were determined in three subgroups of neonates delivered by cesarean section: those delivered by elective section, those delivered by urgent cesarean section for dystocia or failure of labor to progress, and those delivered by section because of fetal distress. Overall, 12.5% of the infants had 1-minute Apgar scores of 4 or less, and 1.4% had 5 minute Apgar scores of 4 or less. Neonates born to mothers given general anesthesia had worse outcomes than those born to mothers given regional anesthesia. Among neonates delivered after elective section, general anesthesia was associated with a higher incidence of low Apgar scores at 1 minute. In neonates delivered by nonelective section, general anesthesia was associated with higher rates of low Apgar scores at 1 and 5 minutes as well as greater requirements for intubation and artificial ventilation. There were no differences seen in neonatal death rates with general and regional anesthesia in the three groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2919766 TI - Surgical repair of hip fractures using continuous spinal anesthesia: comparison of hypobaric solutions of tetracaine and bupivacaine. AB - The aim of this study was to compare hypobaric solutions of tetracaine and bupivacaine in 30 geriatric patients undergoing surgical repair of hip fractures while under continuous spinal anesthesia. Tetracaine 1% and bupivacaine 0.5% were mixed with distilled water to prepare hypobaric 0.25% solutions. In a double blind fashion, all patients received 3 ml (7.5 mg) of either solution in the lateral decubitus position with the operated side up, the table being kept horizontal for 30 minutes after injection. The mean highest sensory levels in both groups, and in both operated and non-operated sides in the same group, were comparable, ranging between T7 and T8.5. Duration of analgesia was 134 minutes with tetracaine and 130 minutes with bupivacaine (NS). In both groups, motor blockade was satisfactory in 29/30 patients on the operated side. The frequency of a decrease in systolic blood pressure of more than 30% was similar in the two groups. The authors conclude that hypobaric solutions of both tetracaine and bupivacaine are suitable for surgical repair of hip fractures in geriatric patients and produce comparable anesthetic and hemodynamic effects. PMID- 2919767 TI - Midazolam-morphine sedative interaction in patients. AB - The sedative effects of midazolam, morphine, and their combination were studied in ASA physical status I and II patients. The visual analog method was used to determine sedative effect. A self-rated score of 50 mm or more on a 100-mm line was regarded as a positive response to the treatment. The dose-response curves for midazolam, morphine, and their combination (each in a group of 30 patients) were determined by probit procedure and compared with isobolographic and algebraic (fractional) analyses. Interactions between midazolam and morphine when used to produce sedation represent summation, not synergism. PMID- 2919768 TI - Left ventricular oxygen tensions in dogs during coronary vasodilation by enflurane, isoflurane and dipyridamole. AB - The purpose of this study was to investigate the effects of the anesthetics enflurane and isoflurane and of the coronary vasodilator dipyridamole on myocardial oxygen balance and myocardial tissue oxygen tensions. The studies were performed in 24 open-chest dogs during basal anesthesia with a narcotic. Myocardial blood flow (MBF) was measured using radioactive microspheres, myocardial surface tissue PO2 by means of a platinum multiwire surface electrode. One control group and three experimental groups were studied: enflurane (1.1 vol%), isoflurane (0.7 vol%, both end-tidal concentrations), and dipyridamole (0.4 mg/kg). Mean arterial pressure significantly decreased to an average of 70 mm Hg in all three experimental groups. Although MBF was unchanged during enflurane (-18%) and isoflurane (+20%), it increased during dipyridamole (+304% p less than 0.05 vs baseline and control, enflurane, and isoflurane groups). Myocardial oxygen consumption decreased significantly during enflurane and isoflurane but remained unchanged during dipyridamole. Thus, the ratio between myocardial oxygen delivery and consumption increased 6% with enflurane (p less than 0.05 vs baseline), 47% with isoflurane (p less than 0.05 vs baseline and control group) and 280% with dipyridamole (p less than 0.05 vs baseline and control, enflurane, and isoflurane groups). Coronary venous PO2 remained unchanged during enflurane but increased significantly during isoflurane and dipyridamole. Left ventricular surface tissue PO2 was unchanged in enflurane and isoflurane animals and decreased slightly, yet significantly, during dipyridamole. All variables remained unchanged in the control group. Thus, isoflurane and dipyridamole interfered with MBF autoregulation and increased myocardial oxygen delivery out of proportion to myocardial demands.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2919769 TI - The effect of cimetidine and ranitidine on the duration of action of succinylcholine. AB - A recent study suggested that cimetidine prolongs the duration of action of succinylcholine (SCh). We examined this reported interaction, and investigated whether it is the result of inhibition of plasma cholinesterase (PChE). We also studied the effect of ranitidine on the duration of action of succinylcholine. Thirty patients were randomly assigned to three groups to receive oral cimetidine 300 mg or ranitidine 150 mg or no H2-antagonist the night before surgery and again 1-2 hours prior to induction of anesthesia. Succinylcholine (1.5 mg/kg i.v.) was given to facilitate tracheal intubation after induction of anesthesia; neuromuscular function was monitored by evoked compound electromyogram. Pretreatment blood samples were analyzed for PChE activity. PChE activity and levels of appropriate H2-antagonists were measured in preinduction blood samples. No significant effect of either cimetidine or ranitidine on the duration of action of SCh or PChE activity was demonstrated. We conclude that H2-antagonists administered preoperatively do not prolong the duration of action of succinylcholine or alter PChE activity. PMID- 2919770 TI - Bunegin-Albin catheter improves air retrieval and resuscitation from lethal venous air embolism in upright dogs. AB - Three types of catheters, the Arrow multi-orifice catheter, the American Edwards 7 Fr Swan-Ganz catheter and the Cook Bunegin-Albin multi-orifice CVP catheter were evaluated for their ability to retrieve venous air emboli and effect on the success rate of resuscitation from venous air emboli. The catheters were inserted in dogs anesthetized with isoflurane (1.7%, inspired) and N2O (66%) in O2 and placed in the sitting position with the head 90 degrees to the horizontal. Swan Ganz catheters were positioned with the right atrial (RA) port just above the junction of the superior vena cava (SVC) and the RA and the pulmonary artery (PA) port in the pulmonary artery. The Arrow and Bunegin-Albin multi-orifice catheters were placed with the proximal orifice just above the SVC-RA junction and the distal orifice near the mid-RA. Dogs were then given a predetermined lethal dose of air (5 ml.kg-1) over 30 sec via the jugular vein. Attempts to aspirate venous air emboli were begun with the first decrease in expired CO2. Both RA and PA ports of the Swan-Ganz catheter were used for aspiration. The amounts of gas retrieved expressed as a percent of the injected air and the incidence of successful resuscitation were compared. Significantly greater percentages of injected venous air were retrieved with the Bunegin-Albin catheter (63 +/- 14%, mean +/- SEM) than with the Arrow multi-orifice catheter (6 +/- 2%) or the Swan Ganz catheter (14 +/- 5%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2919772 TI - Epidural butorphanol-bupivacaine for analgesia during labor and delivery. AB - A double-blind, randomized, dose-response study of a combination of 0.25% bupivacaine combined with 0, 1, 2, or 3 mg of butorphanol was studied in 40 laboring parturients. The optimal dose of butorphanol combined with 8.5 to 10 ml 0.25% bupivacaine was 2 mg; with 2 mg, the duration of analgesia was significantly greater and the time to onset of analgesia significantly shorter than when no butorphanol was added, and the amount of bupivacaine could be reduced 50%. Adverse fetal effects were not observed except that of a low amplitude sinusoidal fetal heart rate pattern with doses of 3 mg butorphanol. All neonatal observations were normal. It is concluded that epidural butorphanol can be a useful and safe adjunct to bupivacaine used for epidural analgesia during labor. PMID- 2919771 TI - Effect of epidural lidocaine on spinal cord blood flow. AB - The effect of epidural lidocaine on spinal cord blood flow (SCBF) was measured in mongrel dogs. Spinal evoked potentials were used to measure spinal cord conduction and enabled us to time the measurement of SCBF associated with maximum reduction in latency and amplitude of spinal evoked potentials produced by instillation of 5 ml of 2% lidocaine in the epidural space. We used the radioactive microsphere technique to quantitate SCBF in the cervical, upper thoracic, lower thoracic, and lumbar regions of the spinal cord. A narcotic/relaxant technique was used to eliminate SCBF changes associated with other anesthetic agents. Other parameters known to affect SCBF were kept constant and within normal physiologic values. As compared with saline solution controls, there were significant decreases in SCBF in all the four areas of spinal cord in animals given epidural lidocaine, most marked in the lumbar area. PMID- 2919773 TI - A computerized anesthesia database. AB - The collection of anesthesia related information in an organized fashion and the subsequent analysis of the data assist in the maintenance of quality anesthesia care. We have created and implemented a computerized anesthesia database that utilizes an IBM personal computer. We are now able to easily and accurately monitor the anesthesia practices of our large university anesthesia program. We recommend the wide adaptation of systems such as ours to all departments, from the small private hospital to the large university center. PMID- 2919774 TI - Epidural morphine after anterior cruciate ligament repair: a comparison with patient-controlled intravenous morphine. AB - To compare the management of postoperative pain using morphine administered by epidural catheter with intravenous patient-controlled analgesia (PCA), we prospectively studied 47 consecutive cases involving repair of the anterior cruciate ligament of the knee. Both the quality of analgesia and the incidence of side effects were documented. Compared with patients receiving PCA morphine, patients given epidural morphine reported significantly lower pain scores both at rest (0.7 +/- 1.1 versus 3.4 +/- 2.1, P less than 0.01) and with mobilization (3.2 +/- 2.1 versus 6.1 +/- 2.1, P less than 0.01). Although patients receiving epidural morphine had a greater incidence of urinary retention, there were no significant differences in the incidence of nausea or pruritus. There was no respiratory depression in either group. We conclude that epidural morphine provides superior analgesia with a clinically inconsequential increase in side effects. Further, epidural morphine may have special advantages when early mobilization is indicated. PMID- 2919775 TI - Epidural analgesia with bupivacaine reduces postoperative paralytic ileus after hysterectomy. AB - This study was undertaken to compare the effects of postoperative bupivacaine epidural analgesia with those of intermittent injections of ketobemidone (a synthetic opioid) on postoperative bowel motility in patients who had had hysterectomies. The epidural group (N = 20) received continuous epidural anesthesia with bupivacaine postoperatively for 26-30 hours and the control group (N = 20) received intermittent injections of ketobemidone for postoperative pain relief. Postoperative bowel movements and propulsive colonic motility were estimated from the first passage of flatus and feces and by following radiopaque markers by serial abdominal radiographs. In the epidural group, the times for first passing of flatus (31 +/- 22 hours; mean +/- SD) and feces (70 +/- 44 hours) were significantly shorter than in the control group (flatus 58 +/- 14 hours and feces 103 +/- 26 hours). The average position of the markers was significantly more distally in the epidural group immediately after operation and the markers continued to move forward during the first postoperative day. In the control group, the markers did not move during this period. The results demonstrate that postoperative bowel peristalsis returned earlier in the patients given epidural analgesia with bupivacaine for pain relief than in patients given a narcotic. PMID- 2919776 TI - Influence of Dornier HM3 system on respiration during extracorporeal shock-wave lithotripsy. AB - Patients undergoing extracorporeal shock-wave lithotripsy (ESWL) for renal stones in the Dornier HM3 apparatus are immersed to the clavicles in water and anchored by abdominal and leg restraining straps. The respiratory effects of this system and sedation with midazolam were studied in 70 awake patients anesthetized with epidural blockade. On immersion, surface abdominal pressure and respiratory frequency (f) increased. Tidal volume (VT) and arterial saturation (SaO2) decreased. After intravenous midazolam 0.045 mg/kg body weight, VT decreased further to 35% below pre-immersion values and stone excursions measured by fluoroscopy diminished by more than 50%; reduction of VT and stone excursions were linearly correlated (R = 0.45). SaO2 declined sharply to 6.1% (range -1.5 13.8%) below pre-immersion values, whereas end-tidal CO2 (PETCO2) increased more slowly and f remained above the pre-immersion rate. In three patients, SaO2 decreased to below 85% but was rapidly restored to 98-100% by oxygen administration. The respiratory effects of sedative drugs are exaggerated by the Dornier HM3 system, and continuous monitoring of gas exchange and appropriate oxygen administration are recommended in patients receiving regional anesthesia and sedation. PMID- 2919777 TI - Selection of implantable narcotic delivery systems. AB - Intraspinal narcotics have dramatically influenced the way pain of malignant origin is managed. There has been a rapid acceptance of this modality within the anesthesia community to treat a wide variety of cancer pain problems. In tandem the development of various implantable narcotic delivery systems has complemented and facilitated the expanded role of intraspinal narcotics in the treatment of cancer pain. Appropriate patient selection is crucial if optimal results are to be achieved. Factors to be considered in patient selection should include the results of the preimplantation spinal narcotic trial, infection trial, infection and local conditions, hematologic status, physiologic and behavioral abnormalities, cost, patient support systems and life expectancy. By interfacing these factors with the unique profiles that each of the five types of implantable narcotic delivery systems offer, improved results both in terms of pain relief and patient satisfaction can be expected. PMID- 2919778 TI - Phonocardiography as a monitor of cardiac performance during anesthesia. AB - The usefulness of phonocardiography as a monitor of cardiac performance during anesthesia was investigated in six dogs. Anesthetic depression by halothane, isoflurane and nitrous oxide was demonstrated by the phonocardiogram. Likewise, the stimulating effect of dopamine clearly showed in the recordings. Changes in the amplitude of the first heart sound were found to correlate closely with changes in the maximum rate of rise of left ventricular pressure (r = 0.9551, 0.001). P less than 0.001). Simultaneous changes in cardiac output and arterial pressure also occurred. Cardiac depression from anesthetics and/or disease is a major concern during anesthesia. Perioperative phonocardiography, a simple and noninvasive procedure, merits further investigation as a possible monitor of cardiac performance. PMID- 2919779 TI - Isoflurane in obstetrics. PMID- 2919780 TI - Evaluation of five metallic tapes for protection of endotracheal tubes during CO2 laser surgery. PMID- 2919781 TI - Interpleural bupivacaine for mammography during needle localization and breast biopsy. PMID- 2919782 TI - Serum inorganic fluoride levels after enflurane in children. PMID- 2919783 TI - Acute bronchospasm complicating intercostal nerve block with phenol. PMID- 2919784 TI - Consecutive cardiac arrests on induction of anesthesia associated with nifedipine induced carotid sinus hypersensitivity. PMID- 2919785 TI - Epidural anesthesia for patients with amyotrophic lateral sclerosis. PMID- 2919787 TI - What wisdom is there in administering elective general anesthesia to children with active upper respiratory tract infection? PMID- 2919786 TI - Concentrations of morphine in the cerebrospinal fluid after femoral perineural morphine administration. PMID- 2919788 TI - Emergency airway management in trauma patients with a suspected cervical spine injury. PMID- 2919789 TI - Recurrent HSVL and the use of epidural morphine in obstetrics. PMID- 2919790 TI - Spinal anesthesia in children: surface anatomy. PMID- 2919791 TI - Is the message getting through? PMID- 2919792 TI - Diltiazem effect on regional function: perfusion pressure rather than direct effect? PMID- 2919793 TI - Another problem with a stylet in an endotracheal tube. PMID- 2919795 TI - Reverse Sellick maneuver. PMID- 2919794 TI - Cuffed endotracheal tubes in pediatric patients. PMID- 2919796 TI - The study of house dust mites in Taiwan. AB - By using a radioallergosorbent test (RAST) and intradermal skin testing, our previous studies strongly suggested that house dust mites are the most important allergen in Taiwan, especially in asthmatic children. This study was conducted to determine the distribution of house dust mites in houses of mite-sensitive asthmatic children and normals, the species of mites in various house dust samples, the seasonal prevalence, and the relation between the content of mite allergen and the mite density in dusts. Serial samples were collected every month between February 1986 and January 1987 from 61 houses of mite-allergic patients and nine normals. About 1 m2 surface area each of (A) family couch, (B) TV room floor carpet, (C) mattress, and (D) bed room floor carpet was vacuumed for one minute. The flotation method was used to collect mites in dusts and mites were counted under an inverted phase contrast microscope. Identification of house dust mite species was also performed. The RAST inhibition method was used for assay of mite allergen in dust extracts. The results showed the following six points. (1) Dermatophagoides pteronyssinus (DP) was the dominant species found in house dust in the Taipei area (78.8%). (2) The mean number of mites was greater in August through November and lowest in July. (3) The content of mite allergen did not correlate with the number of mites in dust sample. (4) The average number of mites in patients' houses was not different from that in normals' houses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2919797 TI - A clinical comparison of terbutaline with albuterol administered by metered-dose inhaler. AB - The effects of albuterol and terbutaline administered by metered-dose inhaler were compared via a randomized crossover design. For 20 previously diagnosed asthmatics, spirometric measurements were determined prior to and at nine times post-dose up to six hours. Patients used each drug for a 7-day test period and recorded the occurrence of side effects. As measured by FEV1 and FEF25-75, both drugs caused a rapid and significant bronchodilation of approximately 4-hour duration. For both drugs, there was little effect on blood pressure and heart rate and reported side effects were minimal. There was no statistically significant difference between drugs in pulmonary response nor in any reported side effect. PMID- 2919798 TI - Studies of neutrophil chemotactic factor of anaphylaxis in metabisulfite sensitivity. AB - The mechanism(s) of adverse reactions to sulfites remains unclear. To determine whether mast cell degranulation is involved in sulfite sensitivity, we performed single-blind, placebo-controlled oral aqueous challenges with potassium metabisulfite in 13 patients with histories suggestive of sulfite sensitivity. Ten patients were also skin tested with potassium metabisulfite at 10 mg/mL and all had negative reactions. Serum samples were obtained from all the patients before the challenge and for 180 minutes after the challenge. The samples were tested for the presence of neutrophil chemotactic factor of anaphylaxis, using both a 51chromium microchamber chemotaxis assay and a leukocyte polarization technique. Six of 13 patients had positive challenges as defined by a fall equal to or greater than 20% in their forced expiratory volume in one second. No significant increase in neutrophil chemotactic factor activity was detected in the postchallenge serum samples from patients who experienced positive or negative challenges. We conclude that sensitivity to aqueous metabisulfite is not associated with mast cell degranulation in metabisulfite skin test-negative patients. PMID- 2919799 TI - Effect of theophylline on adenosine-induced bronchoconstriction. PMID- 2919800 TI - Partial lipodystrophy: immunologic studies in a Sicilian girl. PMID- 2919801 TI - Influence of air pollution on extrinsic childhood asthma. AB - A crossed comparative study was done with 248 extrinsic asthmatic children living either in polluted or non-polluted areas (mean emission per year of sedimentary material greater than or less than 300 mg/m2/day, respectively) to establish the influence of air pollution on childhood extrinsic asthma. The mean number of wheezing crises per year was significantly higher for the children living in polluted areas (10.4 versus 7.69). In addition, incidence of severe asthma (types II, III, and IV) in children living in polluted areas was markedly increased whereas the slight form of asthma (type I) was more frequent in children living in non-polluted areas. No correlation, however, between the wheezing episodes and levels of atmospheric contaminants (fumes and SO2) was detected when a group of 84 extrinsic asthmatic children living in polluted areas was studied longitudinally for a year. The data indicate that air pollution, as an isolated agent, plays a transient role in the appearance of wheezing episodes in subjects with extrinsic asthma. Results also suggest that the air pollution may potentiate wheezing episodes via alternative mechanisms. PMID- 2919802 TI - The use of the dose-response curve in the assessment of normal and asymptomatic asthmatic patients. AB - We studied bronchial reactivity, the slope of the dose-response curve to inhaled methacholine, in normal subjects (N), young asthmatics with normal respiratory resistance (Rrs) (YAL), young asthmatics with high Rrs (YAH), and old asthmatics with high Rrs (OAH) by three different methods: linear reactivity (slope of the linear cumulative dose-conductance (Grs = 1/Rrs) curve), timed reactivity (slope of the log concentration-Grs or time-Grs curve), and log reactivity (slope of the log cumulative dose-Grs curve). There were significant differences in linear reactivity between the N and the three asthmatics but no difference among the three asthmatic groups. On the other hand, both timed and log reactivities showed significant differences between the three asthmatic groups. Log and timed reactivities corrected by baseline Grs did not differentiate the YAL from the YAH but showed a significant difference between the YAH and OAH. This study suggests that timed and log reactivities may be better indices of bronchial reactivity than linear reactivity because they differentiate asthmatics, and that bronchial reactivity in asthmatics may be dependent on not only baseline airway caliber in asthmatics but also other factors such as atopic status or age. PMID- 2919803 TI - Theophylline levels after single daily and divided dosing of a once-a-day theophylline preparation in asthmatic children. AB - Twelve children with chronic asthma were treated with a single dose of sustained release theophylline once-a-day taken after supper at 9 PM. During the steady state period after 15 days of treatment, serum theophylline levels were measured one and two hours after dosing and then every two hours until 9 PM the following day. The peak concentration (mean +/- SD) of serum theophylline (20.9 +/- 6.5 micrograms/mL) was observed eight hours after dosing while the through concentration (4.34 +/- 2.62 micrograms/mL) was measured 24 hours after dosing; the percent fluctuation (mean +/- SD) was 966.45 +/- 1105.55%. Another 15 children were treated with the same preparation administered at 8 AM after breakfast and at 8 PM after supper. Serum samples for theophylline concentration were obtained immediately before dosing at 8 AM and then every two hours for the following 12 hours. The mean theophylline level observed immediately before dosing at 8 AM was 10.16 +/- 3.84 micrograms/mL while the mean level at 8 PM was 9.39 +/- 4.77 micrograms/mL. The peak serum level was 13.07 +/- 5.13 micrograms/mL at 2 PM, while the trough was 9.31 +/- 3.71 micrograms/mL at 10 AM, with a percent fluctuation of 155.21 +/- 147.95%. Few side effects were seen in both groups. The results of our study clearly demonstrated that in children the percent fluctuation and peak-trough differences are far greater with once daily than with twice daily dosing and this should be considered when planning theophylline treatment in asthmatic children. The administration of a once-a-day preparation every 8-12 hours can however result in overlapping absorption patterns. PMID- 2919804 TI - Immunologically medicated food allergy: the importance of food challenge procedure. PMID- 2919805 TI - Polyarthralgias, skin hardening, and weight loss in a 30-year-old male. PMID- 2919806 TI - Metabisulfite sensitivity and local dental anesthesia. AB - A case of sulfite sensitivity first manifesting as urticaria and acute airway obstruction following local anesthesia is described. A positive parenteral provocation test to metabisulfite was observed weeks after recovery of the patient from the clinical event. PMID- 2919807 TI - Reestimations of the protein concentrations of birch pollen allergen extracts selected as candidates for the international standard (IS) preparation. AB - The total protein concentrations of six selected candidates for an international standard (IS) of birch pollen were previously estimated (Ann Allergy 1987;58:71 77). The results of analyses showed large variations depending both on the method and the reference protein used. More than 2-fold variations in the protein content were obtained using Bradford's protein binding method. In the present communication the protein contents of these birch IS-candidates were reestimated by Lowry, a modified Lowry technique, Bradford's protein-dye binding, bicinchoninic acid reagent and amino acid compositions. Great variations were obtained for the protein contents, depending on the technique employed, emphasizing the difficulties of choosing a proper method of protein analyses of pollen allergens. The Lowry and the bicinchoninic acid reagent methods gave the highest obtained protein estimates, while the modified Lowry and Bradford's protein-dye binding methods showed the lowest values. The amino acid analysis gave concentrations similar to those obtained by Lowry and bicinchoninic acid reagent methods. The Lowry method seemed to be adequate for the analysis of plant proteins. The amino acid analysis is currently the most precise method for estimation of the protein concentration irrespective of additional prosthetic groups. A serious shortcoming of the method is that it requires an amino acid analyser or other liquid chromatrographic systems, which are not commonly in laboratory use. PMID- 2919808 TI - Three cases of fatal anaphylaxis to antibiotics in patients with prior histories of allergy to the drug. AB - Three cases of fatal anaphylaxis to penicillin and cephalexin are described. All three patients had prior histories of severe allergic reactions to the antibiotics they were given. The radioallergosorbent test was positive on post mortem blood to the appropriate antibiotic in all three cases. RAST can be performed on post-mortem specimens of serum, sodium fluoride-treated blood, or whole blood. PMID- 2919809 TI - Diagnostic value of IgG4 measurements in patients with food allergy. PMID- 2919810 TI - Resistances and compliances of a compartmental model of the cerebrovascular system. AB - A lumped parameter compartmental model for the nonsteady flow of the cerebrovascular fluid is constructed. The model assumes constant resistances that relate fluid flux to pressure gradients, and compliances between compartments that relate fluid accumulation to rate of pressure changes. Resistances are evaluated by using mean values of artery and cerebrospinal fluid (CSF) fluxes and mean compartmental pressures. Compliances are then evaluated from clinical data of simultaneous pulse wave recordings in the different compartments. Estimate of the average CSF compartmental deformation, based on the compliance between the CSF and brain tissue compartments, proves to be of the order of magnitude of actual experimental measurements. PMID- 2919812 TI - A continuous cardiac output computer based on thermodilution principles. AB - A totally self-contained instrument for the measurement of cardiac output is described. The microcomputer controlled instrument is based upon the principles of thermodilution and is capable of making cardiac output determinations on a minute by minute basis. A bolus of heat is delivered to the blood via a resistive heating element wound on the surface of a conventional thermodilution catheter, and the resulting transient pulmonary artery blood temperature increases is monitored with the thermistor located near the tip of the catheter. The performance of the instrument was tested in a mock circulatory loop and in dogs for periods of up to 13 hours. The accuracy and reproducibility of flow determinations made with the system compare favorably with those made with a conventional cardiac output monitor. This study demonstrates the feasibility of a stand-alone cardiac output computer that can provide virtually continuous measurements of blood flow without the intervention of a technician. PMID- 2919811 TI - A compartmental model for oxygen transport in brain microcirculation. AB - A compartmental model is formulated for oxygen transport in the cerebrovascular bed of the brain. The model considers the arteriolar, capillary and venular vessels. The vascular bed is represented as a series of compartments on the basis of blood vessel diameter. The formulation takes into account such parameters as hematocrit, vascular diameter, blood viscosity, blood flow, metabolic rate, the nonlinear oxygen dissociation curve, arterial PO2, P50 (oxygen tension at 50% hemoglobin saturation with O2) and carbon monoxide concentration. The countercurrent diffusional exchange between paired arterioles and venules is incorporated into the model. The model predicts significant longitudinal PO2 gradients in the precapillary vessels. However, gradients of hemoglobin saturation with oxygen remain fairly small. The longitudinal PO2 gradients in the postcapillary vessels are found to be very small. The effect of the following variables on tissue PO2 is studied: blood flow, PO2 in the arterial blood, hematocrit, P50, concentration of carbon monoxide, metabolic rate, arterial diameter, and the number of perfused capillaries. The qualitative features of PO2 distribution in the vascular network are not altered with moderate variation of these parameters. Finally, the various types of hypoxia, namely hypoxic, anemic and carbon monoxide hypoxia, are discussed in light of the above sensitivity analysis. PMID- 2919813 TI - Analysis of human torso motion with muscle actuators. AB - A biomechanical model is devised to analyze the motion of the human torso and estimate the load on the lumbar spine, the contraction forces in the trunk muscles, and the sensory signals between the muscle and the nervous system. A state space formulation of three-dimensional (3D) equations of motion of the human torso is presented with muscle forces as input to the system. At least 3 pairs of skeletal muscles are considered to be necessary for 3D motion of human torso. Functional anatomy of these major muscles of the human trunk are discussed. These muscles as well as their feedback and feedforward sensory paths are modeled by linear viscoelastic components and force generators. Stability of the torso with three pairs of muscles is studied both with muscle spindles inactive (open loop) and active (closed loop). Voluntary point-to-point motion of the torso in three-dimensional space is simulated on a digital computer, employing a dynamic controller, where feedback gains are tuned (programmed) by higher centers of nervous system. PMID- 2919814 TI - A programmable system for acquisition and reduction of respiratory physiological data. AB - A portable software package (TIDAL--Tools for Intelligent Data Acquisition in the Laboratory) for acquiring and analyzing respiratory physiological data is described. TIDAL supports flow-, volume-, and concentration-measuring devices, and any other instruments that produce linear analog outputs. The system allows users to specify the names and types of channels to be sampled, and the calculations involved in reducing samples to breath-to-breath values. The specification of channels and calculations is given in EDL, an Experiment Description Language designed for respiratory physiology. EDL comprises a set of internal functions (primitives) which can be combined into arbitrarily complex expressions. To simplify EDL programming, TIDAL includes a macro processor and a standard macro library; the library contains definitions for a wide variety of respiratory variables. Examples are inspiratory and expiratory times and total volumes, mean inspired and expired gas volumes and concentrations, and end-tidal concentrations. Variables that are derived from these primary data, such as respiratory quotient, are also easily specified. TIDAL is written entirely in the C programming language, with special attention to portable coding practices. The code is organized in a modular structure that eases porting to multiple hardware/compiler/operating system environments. PMID- 2919815 TI - Cytopathic effects of Moraxella bovis on cultured bovine neutrophils and corneal epithelial cells. AB - The effects of Moraxella bovis on the morphologic features of purified bovine neutrophils and bovine corneal epithelial cells were examined, using transmission and scanning electron microscopy and light microscopy. Within 2 minutes after incubation of bovine neutrophils with living M bovis, electron microscopic cellular changes included vacuolation, swelling, and loss of microplicae. Most of the neutrophils were lysed by 10 minutes of incubation. Human neutrophils phagocytosed the M bovis and remained intact, even after 30 minutes of incubation with the bacteria. Living M bovis killed bovine corneal epithelial cells in vitro. Sterile filtrates prepared from 6-hour shaker cultures of M bovis also killed bovine corneal epithelial cells, but the cytotoxic activity was less than that produced by the living bacteria. Cellular changes were first observed in specimens collected 1 hour after corneal cell monolayers were inoculated with sterile culture filtrates. The changes in these cells included pit-like lesions on the cellular surface, cellular separation, and vacuolation. PMID- 2919816 TI - Development and evaluation of an enzyme-linked immunosorbent assay for bovine antibody (IgG) to Pasteurella haemolytica. AB - The sensitivity of an indirect enzyme-linked immunosorbent assay (ELISA) for bovine IgG serum antibody to Pasteurella haemolytica was compared with that of an indirect hemagglutination (IHA) test. Pasteurella haemolytica serotypes were grown in a chemically defined cell culture medium, and soluble antigens released into the growth medium were used in the ELISA and IHA test. An ELISA with serotype-1 antigen consistently detected antibody in sera that were positive by IHA test (correlation, 99%). Sera reacting with serotype-1 ELISA antigens also reacted with ELISA antigens prepared from other serotypes. Although ELISA titers averaged 5 log2 units higher than IHA titers, plots of titers determined by the 2 methods were approximately linear. Titer increases detected in paired serum samples by either test were similar. The ELISA was more sensitive than was the IHA in detecting colostral IgG antibody in serum of newborn calves. The ELISA uses a simple, stable antigen preparation and detects antibody to P haemolytica serotypes that commonly infect cattle. PMID- 2919817 TI - Humoral recognition of lipopolysaccharide core antigens of gram-negative bacteria in neonatal swine. AB - Serologic recognition of common lipopolysaccharide core antigens has been related to enhanced resistance to gram-negative bacterial disease in several species. Class-specific titers (IgG, IgM) were determined by direct ELISA, using intact Escherichia coli (J5) as a plate antigen. Serum samples were obtained from 224 neonatal swine between the ages of 36 and 60 hours. The mean (+/- SEM) log10 IgG titer against gram-negative core antigens was 1:1,713 +/- 0.4718 and the mean log10 IgM titer was 1:202 +/- 0.5644. The IgG titer was directly related with litter size, birth weight, and serum total IgG concentration; IgM titer was directly related with dam parity and serum total IgG concentration. PMID- 2919819 TI - Electron microscopic study of the unique features and structural-morphologic relationship of canine bone marrow. AB - Electron microscopy revealed several unique features in canine bone marrow, compared with that of other species. The marrow was fatty and extensively trabeculated and was enclosed by a complete layer of endosteal bone-lining cells. Branched reticular cells were closely associated with each other and, occasionally, covered part of the sinus wall as an adventitial layer. The extent of adventitial coverage varied markedly and was less extensive, compared with that of other species. On average, only 23% of the sinus wall was covered by adventitial layer, in contrast to 65% reported in laboratory animals. Unilaminar sinuses, with no adventitial coverage, accounted for greater than 38% of all sinuses. Quantitative analysis indicated that 60% of the latter sinuses contained apertures, as opposed to 35% of sinuses with adventitial coverage (P less than 0.05). Moreover, the number of apertures in unilaminar sinuses was significantly (P less than 0.009) greater than that in multilaminar sinuses. Apertures were observed every 59 microns in unilaminar sinuses, in contrast to every 109 microns in multilaminar sinuses. Approximately 75% of the apertures were occupied by cells in transit, and only 25% were free of cells. Macrophages were distributed throughout the marrow and were closely associated with all blood cell lines. Occasionally, cells that entered the lumen were not fully mature. Erythroblasts were seen migrating across the wall and within the lumen of sinuses. The less extensive adventitial coverage in canine bone marrow might indicate that the rate of cell delivery from the marrow into the circulation was relatively high in this species.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2919818 TI - Porcine malignant hyperthermia susceptibility: halothane-induced increase in cytoplasmic free calcium in lymphocytes. AB - We tested the hypothesis that lymphocytes from swine with susceptibility to malignant hyperthermia (MH) had increased sensitivity to the membrane-perturbing effects of halothane that increase cytoplasmic calcium. Cytoplasmic concentration of ionized calcium in lymphocytes isolated from blood was determined in the presence and absence of halothane for 10 Pietrain x Poland China swine that were susceptible to MH and 20 Yorkshire swine that were resistant to MH. Calcium was determined by dual-emission spectrofluorometry and by measuring the ratio of free to calcium-bound form of the fluorescent calcium dye Indo-1. Mean values for calcium concentrations in lymphocytes from MH-susceptible (MHS) swine were 80% less than control values (40.5 +/- 38.8 and 185.3 +/- 91.6 nmol/L; P less than 0.01). Untreated lymphocytes from MHS swine accumulated calcium at half the rate observed for controls. Exposure to 1 mmol/L halothane resulted in a 3-fold increase of free calcium concentration to 127.9 +/- 81.3 nmol/L in the lymphocytes of MHS swine, but had no significant effect on lymphocytes from control swine (225.0 +/- 91.4; P less than 0.01). Exposure to 2 mmol/L halothane resulted in a 6-fold increase of free calcium concentration to 255.9 +/- 91.4 nmol/L in lymphocytes from MHS swine and a 63% increase in lymphocytes from controls (303.8 +/- 116). The rate of halothane-induced increase in cytosolic calcium was 13 times greater in lymphocytes from MHS swine, compared with controls. These data indicated that the molecular defect that results in halothane-hypersensitivity and is characteristic of muscle of MHS swine also occurs in lymphocytes from MHS swine. PMID- 2919820 TI - Serum and tissue fluid norfloxacin concentrations after oral administration of the drug to healthy dogs. AB - Norfloxacin, a 4-quinolone antibiotic, was administered orally to 4 healthy dogs at dosages of 11 and 22 mg/kg of body weight, every 12 hours for 4 days, with a 4 week interval between dosing regimens. Serum and tissue cage fluid (TCF) norfloxacin concentrations were measured at 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after the first and seventh dose of each dosing regimen. When administered at a dosage of 11 mg/kg, the mean peak serum concentration (Cmax) was 1.0 microgram/ml at 1 hour, the time of mean peak concentration (Tmax) after the first dose. After the seventh dose, the Cmax was 1.4 micrograms/ml at Tmax of 1.5 hours. The Tmax for the TCF concentration was 5 hours, with Cmax of 0.3 microgram/ml and 0.7 microgram/ml after the first and seventh dose, respectively. When administered at a dosage of 22 mg/kg, the serum Tmax was 2 hours after the first dose, with Cmax of 2.8 micrograms/ml. After the seventh dose, the serum Tmax was 1.5 hours, with Cmax of 2.8 micrograms/ml. The Tmax for the TCF concentration was 5 hours after the first and seventh doses, with Cmax of 1.2 micrograms/ml and 1.6 micrograms/ml, respectively. After the seventh dose, the serum elimination half-life was 6.3 hours for a dosage of 11 mg/kg and was 6.7 hours for a dosage of 22 mg/kg. For serum concentration, the area under the curve from 0 to 12 hours (AUC0----12) was 8.77 micrograms.h/ml and 18.27 micrograms.h/ml for dosages of 11 mg/kg and 22 mg/kg, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2919821 TI - Serum vitamin E and blood glutathione peroxidase values of horses with degenerative myeloencephalopathy. AB - Serum vitamin E and blood glutathione peroxidase values were determined in 40 horses with a histologically confirmed diagnosis of degenerative myeloencephalopathy and in 49 age-matched control horses with normal neurologic function. Significant differences were not detected in serum vitamin E or blood glutathione peroxidase values between horses affected with degenerative myeloencephalopathy and control horses. These findings fail to support a reported role of vitamin E deficiency as a cause of equine degenerative myeloencephalopathy. PMID- 2919822 TI - Onchocerca gutturosa and Onchocerca lienalis in cattle: variation in length of microfilariae by site of recovery. AB - Dermal microfilariae recovered from specimens obtained from umbilical and cervical sites of cattle infected with adult Onchocerca gutturosa alone or with adults of O gutturosa and O lienalis were measured and compared with uterine microfilariae obtained directly from gravid female worms of each species. Uterine microfilariae of O gutturosa were longer than dermal microfilariae obtained from cattle harboring only adults of O gutturosa. Dermal microfilariae were recovered from umbilical and cervical sites in these cattle. Those found at the cervical site had lengths equal to or greater than lengths of microfilariae recovered from the umbilical site. There was a significant (P less than 0.0001) shift in length across populations of microfilariae of O gutturosa from various sites in its bovine host, with a progressive decrease in length between microfilariae recovered from the worm's uterus, microfilariae from the cervical dermis, and microfilariae from the umbilical dermis, respectively. A similar direct comparison was not possible for microfilariae of O lienalis, because none of the cattle was infected with only adult worms of this species. In an indirect comparison, microfilariae of O lienalis were identified at the umbilicus, but their presence in the cervical region could not be determined unequivocally because of confounding of microfilariae length by concurrent infection with O gutturosa. Uterine microfilariae from O lienalis were longer than uterine microfilariae of O gutturosa, although a degree of overlap in the range of measurements existed between species. PMID- 2919823 TI - Effects of Moraxella bovis and culture filtrates on 51Cr-labeled bovine neutrophils. AB - The cytotoxicity of Moraxella bovis whole cells and culture filtrates was studied, using 51Cr-labeled bovine and human blood neutrophils. The cytotoxicity of living M bovis was directly related to the concentration of bacteria in the neutrophil cultures, and was maximal at an approximate neutrophil to bacteria ratio of 1:10. Cytotoxicity was maximal by 30 minutes after living bacteria were added to the suspension of the 51Cr-labeled neutrophils. Expression of the cytotoxicity was dependent on the presence of Ca2+ in the media, and was independent of the presence of Mg2+. Cytotoxic activity was eliminated by inactivating M bovis in buffers containing formalin or sodium azide. Hemolytic and nonhemolytic isolates of M bovis were examined for cytotoxic activity. All 7 of the hemolytic isolates were cytotoxic for bovine neutrophils, but all 4 of the nonhemolytic isolates were devoid of cytotoxic activity. None of the 11 isolates were cytotoxic for human neutrophils. Sterile filtrates from 6-hour shaker cultures of a hemolytic M bovis isolate were cytotoxic for bovine neutrophils. Cytotoxicity of the filtrate was eliminated by heating, incubation with trypsin, or addition of EDTA to the media. Bacterial homogenates or sterile filtrates prepared from statistically incubated cultures of M bovis were not toxic for bovine neutrophils. PMID- 2919824 TI - Seminal vesicle and coagulating gland growth induced by intraperitoneal inoculation of fungi in mice. AB - The effect of fungi on the growth of body organs in mice was investigated. Single, intraperitoneal injections of yeasts (Cryptococcus albidus, Saccharomyces cerevisiae, Schizosaccharomyces octosporus) or molds (Aspergillus niger, Geotrichum candidum, Mucor haemalis) induced an increase in the mass of seminal vesicles and coagulating glands independent of whole body weight changes in mice. PMID- 2919825 TI - Comparison of bovine and human platelet deformability, using micropipette elastimetry. AB - We evaluated the deformability of bovine platelets and contrasted the effects of pharmacologic and thermal perturbations on cytoskeletal structure of human and bovine platelets. Platelets were aspirated into micropipettes (0.7 to 0.8 micron in diameter) by stepwise increments in tension. The resulting lengths of the cell extensions were recorded. The cell extensions aspirated from bovine platelets were shorter than the extensions drawn from human platelets. Disassembly of the circumferential microtubule coil allowed human platelets to pass through the pipette, but the same treatments only slightly increased the deformability of bovine platelets. Alteration of the actin filament cytoskeleton caused increased mechanical fragility of human platelets. In contrast, even the combined use of microtubule and actin filament-disrupting agents only modestly increased the deformability of bovine platelets and did not cause premature fragmentation of the cells. Unusual cytoskeletal structure, absence of an open canalicular system, and disparity in granule size may all contribute to the variance in deformability between the platelets of the 2 species. Reduced cell deformability may impair bovine platelet surface interactions by diminishing the ease of cell spreading and formation of areas of contact between the platelet and other cell surfaces. PMID- 2919826 TI - Comparative study of continuous lumbar segmental epidural and subarachnoid analgesia in Holstein cows. AB - Eight adult Holstein cows were used to compare the effects of lumbar segmental epidural analgesia (SEA) and lumbar segmental subarachnoid analgesia (SSA). A modified 17-gauge Huber point (Tuohy) needle was used to place a catheter with stylet into either the epidural space at the thoracolumbar (T13-L1) intervertebral space or the subarachnoid space at the lumbosacral intervertebral junction. The catheters were advanced so that their tips lay at the anterior lumbar (L1-L2) epidural space or at the thoracolumbar (T13-L1) subarachnoid space. The position of the catheter was confirmed radiographically. A 5% solution of procaine HCl was used at mean doses of 300 mg (6 ml) to induce SEA and 84.4 +/ 12.9 mg (1.7 +/- 0.3 ml) to induce SSA. Onset of analgesia to superficial and deep muscular pinprick stimulation was significantly (P less than 0.05) faster in cows with SSA than in those with SEA (10.4 +/- 2.3 minutes vs 15.9 +/- 3.8 minutes). Maximal thoracolumbar analgesia extended from spinal cord segments T12 to L4 on one or both sides of the vertebral column during SEA and from T10 to L3 on one or both sides during SSA. Duration of analgesia lasted significantly (P less than 0.05) longer in cows with SEA than in those with SSA (76.2 +/- 16.2 minutes vs 53.7 +/- 14.3 minutes). The advantages and disadvantages of the SEA catheter technique are discussed. PMID- 2919827 TI - Effects of distention and neostigmine on jejunal vascular resistance, oxygen uptake, and intraluminal pressure changes in ponies. AB - The influence of distention (high baseline intraluminal pressure) and neostigmine methylsulfate on intestinal vascular resistance, oxygen uptake, and intraluminal pressure changes (rhythmic contractions) was studied in terminal jejunal segments, which were perfused at a constant rate, in 16 anesthetized ponies. When baseline intraluminal pressure was increased to 10 mm of Hg, the intestinal vascular resistance and amplitude of rhythmic contractions were increased. Neostigmine induced cyclic increases in amplitude of rhythmic contractions whether intraluminal pressure was 0 or 10 mm of Hg. Neostigmine also increased intestinal oxygen uptake at intraluminal pressures of 0 mm of Hg, but not at 10 mm of Hg, and vascular resistance was not altered at either intraluminal pressure. The results indicate that intestinal hemodynamics are adversely affected by distention. Further, neostigmine did not adversely affect intestinal hemodynamics while increasing rhythmic contractions, suggesting that neostigmine may be useful in the treatment of ileus in equids. PMID- 2919828 TI - Hemostasis development in the lamb fetus and neonate. AB - Fetal and neonatal lamb hemostasis were studied from the 60th day of pregnancy to birth. Platelet counts and blood coagulation, as assessed by tests such as recalcification time and thromboelastography, were similar in fetuses, neonates, and adult sheep. The values of coagulation factors were low, ie, vitamin K dependent Factors II, VII, IX, and X remained unchanged (30 and 40% of adult reference values) until the last 10 days of gestation, and then increased until birth (40 to 60%). Values of fibrinogen and Factor V followed a similar pattern, although their activities became identical to adult values at birth. Also, we measured values of protein C and antithrombin III, which are synthesized by the liver. The importance of hepatic failure and fetal vitamin K deficiency were discussed. Factors VIII and XII activities increased gradually during pregnancy to reach adult values at birth. Fetal fibrinolytic activity increased. This could not be explained by the values of tissue-type plasminogen activator (it was not detectable) or by the presence of its fast-acting inhibitor, whose concentration did not decrease. PMID- 2919829 TI - Concentration of receptors for estradiol and progesterone in canine endometrium during estrus and diestrus. AB - Receptors for estrogen and progesterone were measured in cytosols prepared from specimens of canine endometrium obtained at late proestrus, day 4 of estrus, day 2 of diestrus, and at 10 day intervals from days 10 through 80 of diestrus. Twenty nine adult bitches were used, with 2 to 4 dogs used at each time point. Concentrations of estradiol receptors measured in endometrial cytosols from late proestrus through day 10 of diestrus were similar (mean +/- SEM: 9.9 +/- 2.2, 10.5 +/- 1.2, 16.3 +/- 1.6, and 16.2 +/- 2.9 pmol/g of tissue at proestrus, day 4 of estrus, days 2 and 10 of diestrus, respectively). As serum concentrations of progesterone increased during early diestrus, the concentration of estradiol receptors decreased and were significantly (P less than 0.05) lower on days 30 (4.9 +/- 1.3 pmol/g of tissue) and 40 (3.7 +/- 0.6 pmol/g of tissue) of diestrus. After day 40 of diestrus, when serum concentrations of progesterone were approaching basal concentrations, the concentration of estradiol receptors increased and remained significantly (P less than 0.05) higher from days 60 to 80 of diestrus (day 60, 13.4 +/- 2.9; day 70, 15.7 +/- 1.7; day 80, 19.8 +/- 2.4 pmol/g of tissue). As observed for estrogen receptors, the concentration of endometrial receptors for progesterone also gradually increased from late proestrus (4.9 +/- 1.3 pmol/g of tissue) to day 2 of diestrus (6.4 +/- 0.3 pmol/g of tissue).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2919830 TI - Serum relaxin and progesterone concentrations in pregnant, pseudopregnant, and ovariectomized, progestin-treated pregnant bitches: detection of relaxin as a marker of pregnancy. AB - Serum concentrations of relaxin and progesterone were measured by specific radioimmunoassays in pregnant, pseudopregnant, or ovariectomized (between gestation weeks 4 and 5) pregnant Labrador Retriever bitches. Daily administration of 17 alpha-ethyl-19-nortestosterone was performed to maintain gestation in the ovariectomized pregnant bitches. This synthetic gestagen was selected because it did not interfere with the assay for endogenously secreted progesterone concentration in serum. Serum progesterone concentration was high in ovarian-intact pregnant or pseudopregnant bitches, but the mean progesterone concentration in pseudopregnant bitches (evaluated at 4 weeks after mating) was only 56% of the concentration in pregnant bitches. After ovariectomy, serum progesterone concentration decreased to undetectable values. Unlike progesterone, serum relaxin concentration increased during the latter half of pregnancy in the ovarian-intact and in the ovariectomized pregnant bitches, but relaxin was not detectable at any time in the pseudopregnant bitches. The amount of relaxin measured in the ovariectomized pregnant bitches was less (P less than 0.05) than that in ovarian-intact bitches, suggesting that the ovaries may have contributed to the total circulating relaxin concentration in the latter. Placental production of relaxin might have accounted for the serum relaxin concentration after ovariectomy; thus, the ovary and placenta each may secrete relaxin during gestation in bitches. Regardless of its source, measurement of serum relaxin concentration may offer a useful way of distinction between pregnancy and pseudopregnancy in dogs. PMID- 2919831 TI - Bioassay techniques and high-performance liquid chromatography for detection of oxytetracycline residues in tissues from calves. AB - Tissue specimens from muscle, liver, kidney, and injection sites were collected, and serum was obtained from 3 calves euthanatized on each of posttreatment days 5 and 22. Calves were treated with 6.7, 13.4, or 20 mg of oxytetracycline (OTC)/kg of body weight, IM, once daily for 3 days; these dosages are 1, 2, and 3 times the label dose, respectively. One control calf was euthanatized on each of posttreatment days 5 and 22. In treated male calves killed 2 days after the last injection, OTC residues were detected in all tissues and serum, using high performance liquid chromatography. Tissues from all injection sites also were considered positive for antimicrobial residues, using the swab test on premises (STOP), microbial inhibition test (MIT), and thin-layer chromatography bioautography (TLCB) test. Kidney tissues from a calf given 13.4 mg of OTC/kg and kidney and liver tissues from a calf given 20 mg of OTC/kg also were considered positive, using the MIT and TLCB. Results of the STOP only were considered positive for the liver and kidney of a calf given 20 mg of OTC/kg, but substitution of Saskatoon antibiotic medium-3 for the original medium (antibiotic medium-5) allowed the STOP to detect residues in these tissues from all treated calves. In female calves killed 19 days after the last injection, the STOP, MIT, and TLCB procedures revealed positive results for tissues from some injection sites, but revealed negative results for other tissues.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2919832 TI - Pulsed-wave Doppler evaluation of intracardiac blood flow in 30 clinically normal Standardbred horses. AB - Pulsed-wave Doppler echocardiography was performed on 30 clinically normal 1- to 6-year-old racing Standardbreds. There were 13 females, 13 geldings, and 4 stallions. Cardiac disease was not detected with M-mode, 2-dimensional real-time or pulsed-wave Doppler echocardiography. Normal flow velocities for right and left atrial outflow, right and left ventricular outflow, the aorta, and pulmonary artery were determined. Peak flow velocities for right and left atrial outflow occurred during the rapid filling phase and were higher toward the mitral valve (mean, 0.70 +/- 0.24 m/s) than toward the tricuspid valve (mean, 0.49 +/- 0.17 m/s). Peak flow velocities in the right and left ventricular outflow tracts were similar (means, 0.81 +/- 0.10 m/s and 0.75 +/- 0.39 m/s, respectively). Peak flow velocities in the pulmonary artery (mean, 1.09 +/- 0.42 m/s) and aorta (mean, 1.01 +/- 0.29 m/s) were similar, although flow peaked earlier in systole in the aorta than in the pulmonary artery. PMID- 2919833 TI - Increased peroxidation of erythrocytes of stress-susceptible pigs: an improved diagnostic test for porcine stress syndrome. AB - When incubated with solutions of hydrogen peroxide, erythrocytes of stress susceptible pigs produced more by-products of lipid peroxidation (as measured as thiobarbituric acid-reactive substances [TBARS]) than did erythrocytes from stress-resistant pigs. Using this technique, discrimination between the 2 pig types was absolute at hydrogen peroxide concentrations of 0.9 and 1.5%. This was in contrast to other methods of identifying stress-susceptible pigs, such as osmotically induced erythrocyte lysis and the determination of plasma pyruvate kinase and creatine kinase activities, for which considerable overlap of data was observed between pig types. The increased TBARS production by erythrocytes was further evidence for the existence of an antioxidant abnormality in stress susceptible pigs. However, because there were no discernible differences in the major blood antioxidant-related values between stress-susceptible and stress resistant pigs, the nature of the defect remains unclear. The production of TBARS by erythrocytes when incubated with hydrogen peroxide provides an improved method for identifying stress-susceptible pigs. PMID- 2919834 TI - Clinical studies of fish blood: importance of sample collection and measurement techniques. AB - Effects of blood sample collection and measurement techniques were assessed for blood gas tensions, acid-base status, and hematologic and plasma biochemical values of rainbow trout. Blood samples were collected via intraaortic cannulae from immersed, unrestrained fish and from emersed, restrained fish. The samples were analyzed at either fish body temperature (10 to 14 C) or clinical blood analyzer temperature (37 C); results obtained at 37 C were back-adjusted to fish body temperature, using standard mammalian temperature-correction factors. Fish emersion and handling for 30 seconds significantly (P less than 0.05) altered blood PCO2, acid-base status, and hematologic and plasma biochemical values. The results were consistent with respiratory acidosis and hemoconcentration. The use of mammalian temperature-correction factors for determination of fish blood gas tensions and acid-base status yielded values that were significantly (P less than 0.05) different from those measured directly at fish body temperature. PMID- 2919835 TI - The 1983 Beirut Airport terrorist bombing. Injury patterns and implications for disaster management. AB - The casualty profile and results of the medical care provided for the survivors of the terrorist truck bombing of the U.S. Marine Corps facility in Beirut, Lebanon, in 1983 were reviewed to determine the factors that influenced casualty survival. This explosion resulted in 346 casualties, of whom 234 (68%) were immediately killed. The spectrum of injury was determined in 85 survivors using the Injury Severity Score (ISS). There were seven (6.3%) deaths among the 112 immediate survivors. All deaths occurred among the 19 (17%) victims who were critically injured (ISS greater than 15), giving a mortality in this population of 37 per cent. Six (86%) of the seven deaths were associated with an initial delay in treatment. Head injury was the most common fatal injury among both immediate fatalities (71.4%) and immediate survivors (57%). Thoracic injury and burns each accounted for 29 per cent of survivor deaths. Triage efficiency, as determined by the rates of overtriage (80%) and undertriage (0), did not appear adversely to affect mortality. Critical analysis of disasters such as this can contribute to improvements in preparation and casualty care in the event of future disasters. PMID- 2919836 TI - All terrain vehicles (ATVs). A recreational gamble. AB - Over the period September 1985 to July 1986, the authors reviewed 28 admissions to the Level I trauma center as a result of all-terrain vehicle (ATV) accidents. The patients ranged in age from 6 to 71 years, with nearly 33 per cent (9), under age 16. There were 22 (78.6%) male and 6 (21.4%) female patients. All suffered multiple abrasions, lacerations, and contusions. In addition, 21 (75%) patients had a fracture of some type. Eight (28.6%), had head injuries and 3 (10.7%) sustained spinal cord injuries with a permanent neurologic deficit. Intrathoracic injury occurred in 2 patients (7.1%) and intraabdominal injuries occurred in 1 (3.6%). Moreover, death occurred in 3 (10.7%). Simultaneously reviewed were admissions resulting from motor vehicle accidents (MVA) and motorcycle accidents (MCA) during the same period. By comparison, the death rates (DR), fracture rates (FR), and spinal cord lesions with deficit (SLR) were significantly higher in accidents with ATVs than with MVAs or MCAs. The death rates for ATVs, MVAs, and MCAs were 10.7 per cent, 4.6 per cent, and 1.2 per cent, respectively, with significance between the MCA and ATV groups, P = .0395. The FR were 75 per cent, 53 per cent, and 65 per cent, respectively, with P = .265. SLR was found in 10.7 per cent, 2.3 per cent, and 4.4 per cent of these same groups, with P = .0001. These data suggest that ATV riders are at a higher risk for sustaining fractures, significant spinal cord injuries, or death. ATVs clearly present a health hazard to riders of all ages. PMID- 2919837 TI - Microscopic hematuria after blunt trauma. Is pyelography necessary? AB - Hematuria after blunt abdominal trauma is common with multiple organ system injuries, and many trauma centers routinely perform intravenous pyelography (IVP) on all trauma patients having any degree of hematuria. However, it has been suggested that many IVPs could be avoided if more selective criteria were used. To help determine the need for an IVP, we reviewed the records of 102 consecutive patients undergoing IVP after blunt abdominal trauma over a 17-month period. Twenty-six (25%) patients had gross hematuria. Of these, seven (27%) had abnormal IVPs, and two (7.7%) of those required urologic surgery. Seventy-six (75%) patients had microscopic hematuria. Of these, one (1.3%) had an abnormal IVP but required no urologic surgery. Thus, if IVP had been performed only when gross hematuria was present, then all surgically significant urinary tract lesions would have been recognized, and 75 per cent of these 102 patients would have been spared IVPs. We agree with others that microscopic hematuria alone is not an indication for emergency IVP in these trauma patients. However, gross hematuria or other strong clinical evidence of renal injury still mandates IVP early during the assessment of patients who have suffered blunt abdominal trauma. PMID- 2919838 TI - Trauma in pregnancy. A 10-year perspective. AB - Trauma is the most common cause of nonobstetric death in pregnant women. Fortunately, the incidence of trauma in the pregnant population is low, and individual surgeons are unlikely to see many cases in their practice. This report reviews the Charity Hospital of Louisiana at New Orleans experience with trauma in pregnancy over a recent 10-year period. Our results, with an 8 per cent incidence of maternal death and 28 per cent incidence of fetal death, support the concept of an aggressive approach to resuscitation and evaluation of traumatized pregnant women to achieve optimal results. PMID- 2919839 TI - Penetrating injury to the carotid artery. A reappraisal of management. AB - Penetrating trauma remains the most common cause of cervical carotid artery injury. Controversy persists regarding proper management of these injuries, especially in the presence of a neurologic deficit. Recent experience with 24 patients over a 5-year period is reviewed. In patients with preoperative neurologic deficits, neither repair nor ligation of the injured vessel altered outcome. Outcome correlated only with preoperative neurologic status. All patients without preoperative neurologic deficits should have repair attempted when technically feasible. Although controversial, this study supports carotid artery repair except in comatose patients who have profound neurologic deficits. PMID- 2919840 TI - Sartorius transposition to protect vascular grafts in the groin. AB - Fifty-two patients who required reexploration through the groin incision within seven days of an arterial procedure were studied to assess the value of sartorius transposition. Twenty-four group I patients had the sartorius muscle used to cover the vascular graft at reoperation while 28 group II patients had a standard closure. The groups were similar with respect to age, initial arterial operation, incidence of diabetes, and use of antibiotics and postoperative anticoagulation. Wound complications were frequent in both groups (62.5% vs. 57.1%, respectively) but outcome of these wound problems was quite different. Graft infection and anastomotic disruption were significantly less frequent in group I patients. Because fewer infected prostheses had to be removed group I patients were less likely to require high level amputations. Sartorius transposition is an effective method of protecting vascular grafts jeopardized by the high frequency of wound problems associated with early reoperation. PMID- 2919841 TI - Postoperative bleeding in cardiovascular surgery. Does heparin rebound really exist? AB - Postoperative bleeding following cardiovascular procedures is troublesome and often life-threatening. The effect of heparin (H) is usually reversed with protamine sulfate (P) at the end of vascular procedures; subsequent bleeding or abnormal coagulation times are ascribed to so-called heparin rebound and are treated with extra empiric doses of P. H rebound has heretofore been described only by using biologic clotting tests, which are often abnormal postoperatively. Thus, many instances of postoperative bleeding are treated with inappropriate and dangerous doses of P in the mistaken impression that more H needs to be reversed. Using the new test for plasma H, the azure A Assay, which measures H chemically rather than biologically, 27 patients were tested after cardiac bypass surgery to determine whether H rebound truly exists. Azure A levels of H were measured before the bypass procedure and every half hour from 0-8 hours after bypass in routine coronary artery bypass patients. Tests for prothrombin time (PT) and partial thromboplastin time (PTT) were performed simultaneously. The azure A test was performed on 252 samples of blood in the 27 patients; only one sample drawn anytime except immediately after bypass contained measurable H (0.4%). This sample became negative for H in the ensuing 30 minutes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2919842 TI - Prospective clinicopathologic study of carotid intraplague hemorrhage. AB - A prospective study was conducted of 82 carotid endarterectomy plaques from 73 patients to determine the incidence of intraplaque hemorrhage, its relation to the production of cerebral ischemic symptoms, and the role of the antiplatelets. These included 42 with hemispheric transient ischemic attacks (TIA), nine with hemispheric stroke (Group A), and 31 with nonhemispheric TIA's or asymptomatic carotid stenosis (Group B). The plaques were evaluated for the presence of hemorrhage. Intraplaque hemorrhage was present in 63 (76.8%) of 82; 46 (90.2%) of 51 in Group A had hemorrhage, in contrast to 17 (54.8%) of 31 in Group B (P less than .001). Twenty-nine (56.86%) plaques from patients in Group A had multiple hemorrhages and 22 (43.14%) had single or no hemorrhages; in contrast to two (6.45%) that had multiple hemorrhages and 29 (93.55%) that had single or no hemorrhages in patients in Group B (P less than .0005). Forty-seven plaques were removed from patients receiving antiplatelets; 43 (91.48%) of these showed hemorrhages. Of the 35 plaques that were removed from patients not receiving antiplatelets, 26 (74.2%) showed hemorrhages (P = .071). However, when the plaques were studied for multiple hemorrhages, 28 (59.5%) of 47 had multiple hemorrhages in patients receiving antiplatelet agents in contrast to 3 (8.57%) of 35 in patients receiving antiplatelet agents (P less than .00001). The authors conclude that 1) the intraplaque hemorrhage is an important and common feature in symptomatic carotid disease, 2) antiplatelets increase the incidence of plaque hemorrhages, particularly multiple hemorrhages that carry higher incidence of symptoms. Therefore the use of antiplatelet agents in certain patients with carotid artery disease is questioned. PMID- 2919843 TI - Pancreatitis and duodenal obstruction after aortic surgery. AB - Three patients developed pancreatitis and duodenal obstruction after aortic surgery, contributing significantly to stormy postoperative courses. Serum amylase and lipase levels should be obtained in any patient who has duodenal obstruction and/or persistent ileus after aortic surgery. If these enzyme levels are elevated, computerized tomography of the abdomen should be performed to implicate or exclude pancreatitis as a possible cause. PMID- 2919844 TI - Late complications of traumatic arteriovenous fistula. Case report and overview. AB - Traumatic arteriovenous (AV) fistulas produce several profound pathophysiologic and structural changes in the circulatory dynamics of the vessels associated with the fistula. Most of the changes are reversible with surgery. However, in longstanding AV fistulas, irreversible degenerative changes occur in the arterial wall and result in dilatation and thrombosis. This can make late closure technically difficult. This report presents a case of peroneal AV fistula of 18 years duration. The diagnosis, management, and complications of long-standing AV fistulas are discussed. PMID- 2919845 TI - Splanchnic venous obstruction. A complication of chronic pancreatitis. AB - A retrospective review of 20 adult patients with splanchnic venous obstruction secondary to chronic pancreatitis was performed to identify factors important in the preoperative diagnosis and operative management of this disorder. Fifteen patients with isolated splenic vein obstruction, four with portal occlusion and one with isolated inferior mesenteric vein occlusion were studied. Chronic alcoholism was the etiology of the pancreatitis in 18 patients; two patients had a Type IV hyperlipidemia. Four patients with massive hemorrhage from gastric varices were treated with splenectomy. Most patients presented with complaints of chronic pancreatitis, requiring pancreaticojejunostomy to treat the underlying pancreatic disorder. Splenic artery inflow control was obtained preoperatively in six patients and offers a technique that is beneficial in decreasing operative blood loss. The dynamic computerized tomography (CT) scan was a valuable diagnostic tool in identifying splanchnic venous obstruction although selective angiography is required for confirmation of the diagnosis. PMID- 2919846 TI - Changes in oxygenation and pulse rate during endoscopy. AB - Continuous monitoring of arterial oxygen saturation and heart rate with a pulse oximeter was performed in 100 consecutive patients undergoing esophagogastroduodenoscopy (78) or colonoscopy (22). Twenty-four patients had decreases in their estimated arterial PO2 level to less than 60 mm Hg during or just after the procedure. In 15 patients the hypoxemia was transient, but in nine others, treatment was required. Twenty patients also developed a tachycardia greater than 120 beats/minute. PMID- 2919847 TI - Controlled trial methodology and progress in treatment of the acquired immunodeficiency syndrome (AIDS). A quid pro quo. PMID- 2919848 TI - Style notes: taxonomic names in microbiology and their adjectival derivatives. PMID- 2919849 TI - Nebulized albuterol for acute hyperkalemia in patients on hemodialysis. AB - STUDY OBJECTIVE: To determine the efficacy and safety of nebulized albuterol in the acute treatment of hyperkalemia in patients on chronic hemodialysis. DESIGN: Prospective, double-blind, and placebo-controlled study. SETTING: Outpatient hemodialysis clinic at a university medical center. PATIENTS: Ten patients on maintenance hemodialysis who had chronic hyperkalemia. INTERVENTIONS: Patients received nebulized albuterol therapy (10 mg or 20 mg) or placebo (saline) on three separate occasions, serial measurements of plasma potassium levels, blood pressure, and pulse were then taken for a 2-hour period. MEASUREMENTS AND MAIN RESULT: Patients had a significant decrease in plasma potassium concentrations that was evident by 30 minutes and sustained for at least 2 hours after albuterol treatment. After the administration of 10- and 20-mg doses of albuterol, the maximal decrease in the plasma potassium levels was 0.62 +/- 0.09 and 0.98 +/- 0.14 mmol/L (SE), respectively. Nebulized saline administration did not produce a significant change in the plasma potassium concentrations. Patients did not develop symptoms or significant changes in blood pressure or heart rate with albuterol treatment. CONCLUSIONS: In the doses used, nebulized albuterol therapy resulted in a prompt and significant decrease in the plasma potassium concentrations in patients on hemodialysis, and caused no adverse cardiovascular effects. This treatment should be considered as an important adjunct for acute treatment of serious hyperkalemia in this population of patients. PMID- 2919850 TI - Osteoporosis in hemochromatosis: iron excess, gonadal deficiency, or other factors? AB - STUDY OBJECTIVE: To define the prevalence, severity, type and pathogenesis of osteopenia in idiopathic hemochromatosis. DESIGN: Prospective study conducted over 18 months. SETTING: Tertiary care center. SUBJECTS: Twenty-two men with idiopathic hemochromatosis and 20 age-matched controls. There were 5 hypogonadal patients, 9 eugonadal nonvenesected patients, and 8 eugonadal venesected patients. MEASUREMENTS AND MAIN RESULTS: All patients and controls were evaluated by spinal radiography, spinal and forearm bone mineral density estimations, dynamic skeletal histomorphometry, and serum biochemistry. Ten patients (45%; 95% CI, 24% to 68%) had osteoporosis as defined by spinal and forearm bone density measurements. Trabecular bone volumes were significantly reduced in the patients (the difference in means between patients and age-matched controls was 3.9%; CI, 1.3% to 6.7%). No patient had osteomalacia. Hypogonadal men had lower bone mass measurements than eugonadal men (radial bone density: beta coefficient = -20.5; CI, -29.2 to -11.8; trabecular bone volume: beta coefficient = -7.1; CI, -10.8 to -3.3). Osteoid and osteoblastic surfaces and bone formation rates were significantly greater in the eugonadal venesected compared with the eugonadal nonvenesected persons (P less than 0.05 for all measurements). CONCLUSIONS: A significant decrease in bone density is seen in idiopathic hemochromatosis, particularly when hypogonadism is present. Low serum free-testosterone concentrations rather than the calciotrophic hormones determine bone mass in this condition. PMID- 2919851 TI - Unilateral renal parenchymal disease with contralateral renal artery stenosis of the fibrodysplasia type. AB - In patients who have hypertension and a unilateral small kidney, hypertension may have either a vascular (renal artery stenosis) or nonvascular (urologic) cause. Generally, the hypertension can be attributed to the abnormal-sized kidney, and nephrectomy of the shrunken kidney or correction of the stenotic artery will result in the normalization of blood pressure. We report eight cases of hypertension in young women shown to have a small kidney by intravenous urography. The abnormal-sized kidney was considered to be due to either agenesis or dysplasia and reflux. Although the diseased kidney was thought to be the cause of the high blood pressure, these patients were unique in that they had a stenosis of the contralateral renal artery of the fibrodysplasia type, which was predominantly localized in the distal part of the artery and frequently extended into the peripheral branches. Successful anatomic correction of the stenotic artery without surgery on the contralateral small kidney resulted in the normalization of blood pressure. This previously unrecognized combination of parenchymal disease of one kidney and renal artery stenosis of the fibrodysplasia type on the contralateral side should be considered in patients with hypertension and a unilateral small kidney. Such recognition could prevent the unnecessary treatment of these patients with an angiotensin-converting enzyme inhibitor or nephrectomy. PMID- 2919852 TI - The misinformation era: the fall of the medical record. AB - Medical record information has become less reliable than ever before despite the electronic information revolution in medical care and the authority medical records have been accorded in our society. Long flawed by errors introduced by medical personnel, patients, and machines, medical records have had a further decline in credibility as a result of the loss of confidentiality and the imposition of well-meaning but unrealistic cost-control regulations on medical practice. Medical records are being distorted and fashioned to keep clinically important but sensitive personal information about patients from public view. To comply with standards of care and a reimbursement system blind to biologic diversity, medical records are being forced to address only the technical side of care. Until these deficiencies are corrected, our increasing dependence on medical records should be balanced by increasing skepticism about the value of the information they contain. PMID- 2919853 TI - Evaluation of patients after recent acute myocardial infarction. American College of Physicians. PMID- 2919854 TI - Ischemic hepatitis from aortic dissection. PMID- 2919855 TI - Therapy for syphilis. PMID- 2919856 TI - Right-sided endocarditis with Staphylococcus aureus. PMID- 2919857 TI - Effects of social class differences and social mobility on growth in height, weight and body mass index in a British cohort. AB - By longitudinally linking follow-up restudies of the National Child Development Study it has been possible to examine not only the well-known association of social class with the size of the child, but also with longitudinal growth, and, in addition the effect of social mobility on growth. The relation of type of occupation of the male head of household to height and weight of the child is seen at all ages (7, 11 and 16) but class influence on growth from 7 years onward is minimal. Social mobility is a significant factor especially in relation to stature but is not significantly related to growth after age 7 so the effect of underlying conditions on the children precedes the change of type of occupation by their fathers. PMID- 2919858 TI - Acute mountain sickness and physiological stress during intermittent exposure to high altitude. AB - The effect of intermittent exposure to high altitude (4200 m) hypoxia on symptomatology of acute mountain sickness (AMS) was observed, and the relationship between AMS and stress hormone excretion was examined among shift workers at the United Kingdom Infrared Telescope (UKIRT) facility and a control group of sea level residents. Some of the shift workers experienced AMS during their first day at altitude, but had recovered after 5 days residence at altitude. Upon acute exposure to altitude, none of the shift workers reported severe cases of AMS after 5 days residence at sea level, but some reported severe cases after 45 residence at sea level, thus providing some evidence for a 'carry over' of acclimatization for a 5 day period. Reported symptomatology at sea level was predictive of 24 h. excretion rates of adrenaline and 17 hydroxycorticosteroids at high altitude. No good predictors of symptomatology of AMS at high altitude were found using sea level measures alone. PMID- 2919859 TI - Birth dimensions in Melanesian and Indian Fijians and their relationships with maternal and socio-economic factors. AB - Fifty-nine Melanesian (MF) and 39 Indian (IF) Fijian full-term newborns were studied within 5 days of birth. Dimensions recorded included birthweight, length, crown-rump length, head circumference, upper limb length, bycondylar humeral and femoral diameters and four skinfolds (triceps, subscapular, suprailiac and thigh). Data from previous pregnancies of the presenting newborns' mothers were added to presenting birthweights, giving a total of 160 MF and 84 IF birthweights. In all birthweight and linear dimensions MFs were the bigger. Sex differences were significant in respect only of head circumference and the two bicondylar diameters. Multiple regression analysis showed dimensions in MF newborns to have few significant relationships with the maternal and socio economic variables of age, parity, stature and years of education, but IFs had many more significant relationships. When covariance correction was made for the significant maternal and socio-economic variables (maternal age and parity) little effect on racial differences was seen. All linear dimensions except length could be subsumed into birthweight. MFs had greater triceps and subscapular skinfold thicknesses than IFs, a difference which was not much changed by covariance correction for significant maternal and socio-economic variables (maternal stature and years of education). Measurements of shape, expressed as ratios of linear dimensions, showed few racial differences but males had relatively broader limbs. For upper limb shape only, this difference was maintained after covariance correction for significant maternal and socio economic variables (parity, stature and education). The greater size of MF infants at birth is associated with lower peri- and neonatal death rates. However this advantage is reversed during the remainder of the first year of life. It is suggested that better standards of infant care among IFs are responsible for this change. PMID- 2919860 TI - The validity of reported parental height in inner city areas in England. AB - The validity of self-reported height was assessed in a sample of Afro-Caribbean, Asian and Caucasian parents. Asian mothers overestimated their height (p less than 0.01) and Caucasian mothers overestimated that of their child's father. The standard deviations of the differences between reported and measured height, with the exception of Caucasian mothers, were large (between 4.33 cm and 11.18 cm). It is concluded that self-reported height from subjects living in inner city areas in Britain should be interpreted with great caution. PMID- 2919861 TI - Variability in stature growth. AB - An analysis of longitudinal data shows that there are marked changes in the variability of stature and stature velocity during growth in stature, as measured by the coefficient of variation. Variability in stature velocity tends to rise after birth but from age 2 years it gradually declines until the end of adolescence, once variation in the timing of adolescence is taken into account. Comparison of velocity variation in an affluent western society (UK) with velocity variation in two poorer societies (India and Thailand) shows the former to be systematically smaller. PMID- 2919862 TI - Distribution of group-specific component (Gc) subtypes in several Mongoloid populations of East Asia. AB - The distribution of group-specific component (Gc) subtypes was determined by isoelectric focussing in thin layer polyacrylamide gels of pH range 4 to 6.5, in a group of 2412 individuals from 10 Mongoloid populations of East Asia. The sample comprised 959 Chinese from different localities (Singapore, 249; Malaysia, 347; Taiwan, 246; Hong Kong, 57; Fuzhou mainland, 60), 338 Koreans, 277 Filipinos, 484 Thais, 330 Malays and 24 Indonesians. The Filipinos and Malays had lower frequencies of Gc2 (0.15 and 0.18) compared to other Mongoloid populations (0.23 to 0.32) and the Chinese (0.24 to 0.32). The frequencies of Gc1F varied from 0.39 to 0.49 in the Chinese and 0.35 to 0.52 in other Mongoloid populations. Low frequency of rarer variants was observed in most of the populations. The average frequency of Gc2 was higher in the Japanese (0.26 +/- 0.01) than in the Chinese (0.24 +/- 0.02), and in Mongoloids of East Asia (0.23 +/- 0.01) and South East Asia (0.17 +/- 0.01). The average frequencies of Gc1F and Gc1S were similar in the Chinese and Japanese, whereas the Mongoloids of South-East Asia had a much higher frequency of Gc1F and a lower frequency of Gc1S than the Chinese, Japanese and East Asian Mongoloid populations. PMID- 2919863 TI - The Ok Tedi Health and Nutrition Project, Papua New Guinea: adult physique of three populations in the North Fly region. AB - Adult physiques of three populations living close to a major gold and copper mine are described and compared. Men of all three groups do not differ in stature, sitting height, biceps, triceps, subscapular and medial calf skinfold thicknesses. However, Wopkaimin men are heavier, with bigger mid-upper arm circumference and bi-iliac diameter than their Ningerum and Awin counterparts. Women of all three groups have similar stature, sitting height, biacromial diameter, biceps and triceps skinfold thicknesses. Wopkaimin women have greater values for mid-upper arm and calf circumference, subscapular, supra-iliac and medial calf skinfold thicknesses, and bi-iliac diameter. These differences are attributed to an increase in the plane of nutrition of the Wopkaimin, who live closest to, and have been most affected by the Ok Tedi gold and copper mining operation. PMID- 2919864 TI - Effect of sex chromosome aneuploidy on growth of human skin fibroblasts in cell culture. AB - Growth of human skin fibroblast lines with sex chromosome aneuploidy was studied in cell culture. Two lines were derived from individuals with 45,X and two from individuals with 47,XYY chromosome constitution. The aneuploid cell lines were compared with normal skin fibroblasts derived from age-matched same-sex siblings. To ensure similar conditions in culture, each study-control pair was treated simultaneously and equally in all steps. Growth in both 45,X cell cultures slowed down earlier than in control cultures. One of the 47,XYY cultures grew faster and the other at a similar speed to the control culture. Thus, the 45,X cell lines seemed to have lesser, and one of the 47,XYY cell lines greater, growth potential than the 46,XX and 46,XY cells, respectively. These differences in the final cell numbers may relate to changes in the rate of cell division of the aneuploid cell lines. However, the results do not support the hypothesis that an increasing number of sex chromosomes decreases the rate of cell division. PMID- 2919865 TI - Gray-matter degeneration in presenile Alzheimer's disease. AB - Previous comparisons between presenile Alzheimer's disease (AD) and senile dementia of the Alzheimer type (SDAT) did not control for disease severity and duration. In the current study, 18 patients with each diagnosis were matched for disease duration, cognitive dysfunction, and behavioral symptoms (using the modified Mini-Mental Status [mMMS] examination and the Blessed Dementia Rating Scale [BDRS] ). Regional cerebral blood flow (rCBF) was quantified by the 133xenon inhalation technique, and several indices of tissue perfusion were examined. The two variables of primary interest were relative gray-matter relative weight (35% in presenile patients versus 39% in senile patients and healthy control subjects, p = 0.006), with neither perfusion nor disease severity differences between the two dementia samples. This loss of gray matter was significantly related to both severity and duration of disease in the patients with presenile AD, but not in patients with SDAT. These findings lend support ot previous suggestions of greater degenerative process in presenile AD and confirm the need to examine and control age of onset in future investigations of AD. Further, correlation analysis suggests greater proportion of common variance among clinical and physiological indices in presenile AD. PMID- 2919866 TI - The olfactory and cognitive deficits of Parkinson's disease: evidence for independence. AB - In the present study we sought to determine whether the olfactory deficits of parkinsonism are related to the cognitive and perceptual-motor manifestations of the disease. Pearson correlation coefficients were computed among a number of olfactory, neurological, and neuropsychological measures obtained from 58 Parkinson's disease patients, including the University of Pennsylvania Smell Identification Test, a modified Randt memory test, a reaction time test, a finger tapping test, ratings of motor and neurological function, and selected verbal and performance subtests of the Wechsler Adult Intelligence Scale--Revised. Data from 38 patients with Parkinson's disease who received odor detection threshold testing were also evaluated. The intercorrelation matrix was subjected to a principal components factor analysis which yielded six clear-cut factors: cognitive/memory, gross motor, oral motor, fine motor, olfactory, and tremor. The olfactory factor received strong and nearly exclusive loadings from the olfactory measures (which did not evidence meaningful loadings on any of the other factors). A ten-trial jackknife procedure revealed the factor structure to be stable. Further support of the independence of the olfactory variables from the other measures was provided by multiple regression and canonical correlation analyses. Overall, these findings lend support to the hypothesis that the olfactory disorder of parkinsonism is independent of the cognitive, perceptual motor, and memory manifestations of the disease. PMID- 2919867 TI - Hypoxic-ischemic spinal cord injury following perinatal asphyxia. AB - The role of spinal cord injury in the pathogenesis of abnormal motor signs (depressed tone and reflexes) following severe perinatal hypoxia-ischemia was prospectively evaluated by clinical, electrophysiological, and neuropathological examinations in 18 asphyxiated neonates. All infants had an abnormal mental status (lethargy or coma), and seizures were present in 12. Neuromuscular examinations revealed hypotonia or flaccidity and hyporeflexia or areflexia in all infants. Neuropathological examinations of the cerebrum and spinal cord were conducted in the 12 neonates who expired. Cerebral pathological findings included cortical neuronal necrosis in 10 of 12 and subcortical white matter injury in 5 of 12. All infants with coma or seizures displayed diffuse cortical injury, but no injury conformed to a parasagittal "watershed" distribution. Spinal cord gray matter displayed prominent ischemic necrosis in 5 patients who were typically flaccid and areflexic. Electromyographic examinations of all 6 survivors were abnormal, consistent with recent injury to the lower motor neuron above the level of the dorsal root ganglion. We conclude that ischemic injury to anterior horn cells within spinal cord gray matter is relatively common among hypotonic hyporeflexic neonates following severe perinatal hypoxia-ischemia. Although the acute neurological syndrome of neonatal asphyxia is often overshadowed by prominent cerebral signs such as coma and seizures, the motor abnormalities may be partially attributed to concurrent spinal cord injury. PMID- 2919868 TI - Carbamazepine and its epoxide: relation of plasma levels to toxicity and seizure control. AB - We studied the relation of plasma levels of carbamazepine (CBZ) and carbamazepine 10,11 epoxide (CBZ-E), and their ratio to drug toxicity and seizure control in 7 patients with complex partial seizures. CBZ-E/CBZ increased with increasing CBZ levels and was higher when patients were taking phenytoin or valproic acid. There were weak correlations between CBZ, CBZ-E levels, toxicity scores, and seizure control when patients were taking CBZ alone, but not when other drugs were given as well. There were no significant differences in the correlation with toxicity score or seizure frequency between CBZ, CBZ-E, or their sum. Measurement of CBZ-E levels did not provide additional information useful for monitoring clinical response to CBZ therapy. PMID- 2919869 TI - The open opercular sign: diagnosis and significance. AB - Four children with varying clinical manifestations, but with the unifying feature of severe developmental delay, had bilateral enlargement of the sylvian fissure confirmed by magnetic resonance imaging (MRI). Subsequently, we examined 125 consecutive MRI scans of the heads of pediatric patients, looking for this insular exposure, and did not find it. Pathological correlation in 1 child revealed arhinencephaly and abnormal gyral formation; another is known to have migrational abnormalities. We suggest that the open operculum is a sign of arrested development and is associated with other anomalies and a poor prognosis. PMID- 2919870 TI - Nonconvulsive status epilepticus following cerebral angiography. AB - A 64-year-old man developed lethargy and aphasia immediately following cerebral arteriography with iothalamate meglumine. An electroencephalogram showed continuous epileptiform activity. The patient was treated with intravenous phenytoin with complete resolution of clinical symptoms and electroencephalographic epileptiform abnormalities. The diagnosis of nonconvulsive status epilepticus should be considered in cases of altered consciousness following cerebral arteriography. PMID- 2919871 TI - Transient neonatal hyperglycinemia. AB - Two patients with neonatal seizures and subsequent normal neurological development were found to have nonketotic hyperglycinemia. In both patients, hyperglycinemia resolved at 6 weeks of age. After cerebrospinal fluid glycine levels were normalized, the seizures stopped completely in one child and were markedly improved in the other. The possible mechanisms for the hyperglycinemia are discussed. PMID- 2919872 TI - Disseminated thymoma and myasthenia gravis: dramatic response to prednisone. PMID- 2919873 TI - Ocular motor paresis versus apraxia. PMID- 2919874 TI - "Ease of falling" syndrome. PMID- 2919875 TI - Essential tremor and Parkinson's disease. PMID- 2919876 TI - tert-butyl hydroperoxide kills cultured hepatocytes by peroxidizing membrane lipids. AB - The killing of cultured hepatocytes by tert-butyl hydroperoxide was dissociated from the changes both in glutathione metabolism and in intracellular calcium homeostasis that accompany the metabolism of this toxin. Deferoxamine, a ferric iron chelator, keto-methiolbutyric acid, a radical scavenger, and the antioxidants N,N'-diphenyl-p-phenylenediamine (DPPD) and catechol prevented the cell killing without effect on glutathione or calcium metabolism. Malondialdehyde, formed as a result of the peroxidation of cellular lipids, accumulated before any loss of viability. Prevention of the lipid peroxidation paralleled the prevention of cell killing. As much as 25 microM DPPD or 1 mM catechol did not prevent the iron-dependent, catalase-insensitive formation of tert-butyl alkoxyl radicals. Thus, DPPD and catechol do not detoxify a radical species that kills the cells and initiates lipid peroxidation as an epiphenomenon. Furthermore, lipid peroxidation cannot be dismissed as simply a consequence of the cell killing. It is concluded that low concentrations of tert butyl hydroperoxide (less than 1.0 mM) lethally injure cultured hepatocytes by a mechanism that depends on the peroxidation of cellular lipids. PMID- 2919877 TI - Purification and characterization of a galactoside-binding lectin from human brain. AB - A beta-galactoside-binding hemagglutinin was detected in soluble extracts of human brain. This soluble lectin was purified to homogeneity by affinity column chromatography on lactose coupled to divinylsulfone-activated agarose. The purified lectin had an isoelectric point of 3.9 and its subunit molecular mass estimated by polyacrylamide gel electrophoresis in sodium dodecyl sulfate was 14,500. Human brain lectin was not a glycoprotein and its amino acid composition was characterized by a high content of serine, glutamic acid, and glycine, and a low content of methionine and cysteine. The most potent saccharide inhibitors tested were thiodigalactoside, lactose, and p-nitrophenyl-beta-D-galactoside. An antibody was raised to the pure lectin. Immunological relationships were found between the brain lectin and several other soluble lectins of various vertebrate origins. PMID- 2919878 TI - Formation of trans-caffeoyl-CoA from trans-4-coumaroyl-CoA by Zn2+-dependent enzymes in cultured plant cells and its activation by an elicitor-induced pH shift. AB - A novel hydroxylase activity catalyzing the formation of trans-caffeoyl-CoA from trans-4-coumaroyl-CoA was identified in crude extracts from cultured parsley cells. The extracts were less active (Vmax/Km) in converting trans-4-coumaric to trans-caffeic acid. Optimal hydroxylase activity was found at pH 6.5 with a steep decline toward both pH 7.4 and pH 5.0. The enzyme activity requires ascorbate and Zn2+ at optimal concentrations of 50 and 0.5 mM, respectively. No other reductant could replace ascorbate, whereas high concentrations of Ca2+ partially substituted for Zn2+. The enzyme is soluble and appears to be located in the cytoplasm. The unusual pH optimum suggests that the hydroxylase is inactive at the normal cytoplasmic pH. Upon treatment of parsley cells with an elicitor derived from Phytophthora megasperma f. sp. glycinea, the cytoplasmic pH dropped by approximately 0.25 pH unit within 55 min as determined by 31P NMR spectroscopy. Our results suggest that this shift in the cytoplasmic pH is sufficient for the activation of the hydroxylase, eventually leading to the formation of caffeoyl and feruloyl esters. Such esters may be a part of a very rapid resistance response of the plant cells, which would leave no time for de novo enzyme synthesis. PMID- 2919879 TI - Dissociation of ferritins. AB - Apoferritins prepared from horse spleen and heart and rat heart and liver were dissociated by treatment with acetic acid (pH 1.3-3.0). Sedimentation velocity studies showed that apoferritins of spleen and liver (16-17 S) and heart (18-19 S) dissociated into material sedimenting near 3.2 S. Sedimentation equilibrium measurements determined that most of the material had a molecular weight of 38,000-43,000, corresponding to subunit dimers. Failure to dissociate into subunit monomers was confirmed by gel chromatography on Sephadex G-75 and G-150. With the exception of boiling in sodium dodecyl sulfate, further treatments with 0.1-0.4 M KCl, NaCl, 4-9 M urea, 0.01-0.5 M KSCN, 0.1-0.5% Triton X-100, 5-52% dimethylsulfoxide, 10% ethylene glycol, or 0.1% trifluoroacetic acid all failed to cause dissociation into individual subunits, as did exposure to 6 M guanidine HCl or formic acid, or prior succinylation and/or nitration of the protein. Reassociation occurred between pH 4 and 7 but was not aided by the addition of Fe(II) or reducing agents. It is concluded that ferritins readily dissociate to subunit dimer units and that further dissociation does not occur without full denaturation of the protein. PMID- 2919880 TI - Monoterpene biosynthesis: mechanistic evaluation of the geranyl pyrophosphate:(-) endo-fenchol cyclase from fennel (Foeniculum vulgare). AB - Geranyl pyrophosphate:(-)-endo-fenchol cyclase catalyzes the conversion of geranyl pyrophosphate to (-)-endo-fenchol by a process thought to involve the initial isomerization of the substrate to the tertiary allylic isomer, linalyl pyrophosphate, and the subsequent cyclization of this bound intermediate. Studies with 18O-labeled acyclic precursors and H2(18)O, followed by mass spectrometric analysis of the cyclic product, confirmed that water was the sole source of the carbinol oxygen atom of endo-fenchol, thus indicating the participation of the solvent in terminating this presumptive carbocationic reaction. The isomerization component of the normally coupled reaction sequence was demonstrated directly using the substrate analog 2,3-cyclopropylgeranyl pyrosphosphate and by isolating the corresponding homoallylic analog of linalyl pyrophosphate as a major reaction product. The cyclization component of the reaction sequence was effectively dissected using linalyl pyrophosphate as substrate, and both isomerization and cyclization steps were shown to take place at the same active site of the cyclase, an observation consistent with the efficient coupling of these processes. 2-Fluorogeranyl pyrophosphate and 2-fluorolinalyl pyrophosphate were shown to be effective inhibitors of the cyclase, and the electron-withdrawing substituent was shown to greatly suppress the rate of cyclization of these labeled analogs, indicating that both steps of the coupled isomerization cyclization sequence are initiated by ionization of an allylic pyrophosphate. Additional evidence for the electrophilic nature of the reaction was obtained by demonstrating the ability of the cyclase to solvolyze other substrate analogs which bear an allylic pyrophosphate, and by showing that cyclization was strongly inhibited by sulfonium analogs of presumptive carbocationic intermediates of the reaction sequence, especially in the presence of inorganic pyrophosphate as counterion. In spite of the fact that the fenchol cyclase terminates the cyclization with an external nucleophile (H2O), the primary mechanistic features of this isomerization-cyclization reaction are similar to those catalyzed by other cyclases that terminate the reaction by deprotonation or cation capture by the pyrophosphate moiety of the substrate. PMID- 2919881 TI - Rat brain hexokinase: further studies on the specificity of the hexose and hexose 6-phosphate binding sites. AB - Based on the lack of correlation between the ability of various hexoses to serve as substrate and the ability of the corresponding hexose 6-phosphates to inhibit brain hexokinase (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1), R. K. Crane and A. Sols (1954, J. Biol. Chem. 210, 597-606) proposed that this enzyme possesses two discrete sites capable of binding hexose moieties, one serving as the substrate binding site and a second, regulatory in function, to which inhibitory 6-phosphates bind. Subsequent work has provided further experimental support for this proposal. The pioneering work by Crane and Sols focused primarily on the specificity of these sites with respect to requirements for orientation of hydroxyl substituents at the various positions of the pyranose ring. The present study explores additional aspects of the specificity of these sites, namely, the effect of substitution of a sulfur atom in place of the oxygen in the pyranose ring on ability to serve as substrate or inhibitor, and the effect of modification in charge of the substituent at the 6-position on inhibitory effectiveness. 5-Thioglucose is a linear competitive (versus glucose) inhibitor of rat brain hexokinase, with a Ki of about 0.2 mM, and is a linear mixed inhibitor (versus ATP), with Ki values in this same range. 5-Thioglucose is not, however, readily phosphorylated by brain hexokinase. Thus, although 5-thioglucose binds with moderate affinity to the glucose binding site, it is not effectively used as a substrate of the enzyme. Inhibition of brain hexokinase by glucose 6 phosphate or its analogs has been found to require a dianionic substituent at the 6-position. The 6-fluorophosphate derivative and glucose 6-sulfate are poor inhibitors of the enzyme, and the Ki for inhibition by 1,5-anhydroglucitol 6 phosphate increases markedly at pH values below the pK of the 6-phosphate group, indicating that the monoanionic form is ineffective as an inhibitor. In contrast to the detrimental effect that substitution of the oxygen atom in the pyranose ring with a sulfur has on ability to serve as substrate, 5-thio analogs are considerably more effective as inhibitors, the Ki for inhibition by 5-thioglucose 6-phosphate being 10-fold lower than that seen with glucose 6-phosphate. This effect of the heteroatom substitution can partially offset the decreased inhibition resulting from monoanionic character at the 6-position, but the 6 fluorophosphate derivative of 5-thioglucose 6-phosphate still inhibits with a Ki about 1000-fold greater than that seen with 5-thioglucose 6-phosphate.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2919882 TI - Directed biosynthesis of avermectins. AB - Avermectin homologs are produced by Streptomyces avermitilis when externally supplied with sodium 2-methylpentanoate and sodium 2-methylhexanoate. The homologs carry 2-pentyl and 2-hexyl groups, respectively, at C-25 of the aglycone moiety as opposed to the 2-butyl group of "a" components and the isopropyl group of "b" components of natural avermectins. The new homologs designated as avermectin "c" and "d" components, respectively, possess potent anthelmintic and insecticidal activity. PMID- 2919883 TI - Essential histidine residues in lysolecithin:lysolecithin acetyltransferase from rabbit lung. AB - Both activities of rabbit lung lysolecithin:lysolecithin acyltransferase (EC 3.1.1.5), hydrolysis and transacylation, are inactivated by diethylpyrocarbonate. The reaction follows pseudo-first-order kinetics, and second-order rate constants of 1.17 mM-1min-1 for hydrolysis and 0.56 mM-1 min-1 for transacylation were obtained at pH 6.5 and 37 degrees C. The rate of inactivation is dependent on pH, showing the involvement of a group with a pK of 6.5. The difference spectra showed an increase in absorbance at 242 nm, indicating the modification of histidine residues. The activity lost by diethylpyrocarbonate modification can be partially recovered by hydroxylamine treatment. The statistical analysis of residual fractional activity versus the number of modified histidine residues leads to the conclusion that two histidine residues are essential for the hydrolytic activity, whereas transacylation activity depends on only one essential histidine. The substrate and substrate analogs protected the enzyme against inactivation by diethylpyrocarbonate, suggesting that the essential residues are located at or near the active site of the enzyme. PMID- 2919884 TI - Active-site modification of superoxide dismutase by H2O2 studied through 1H NMR of the cobalt derivatives. AB - It is known that H2O2 at pH 10, inactivates copper(II)-zinc(II)-SOD although not much information is available on what happens at the ligands coordinated to the two metal ions. We have reinvestigated the system through the electronic and 1H NMR spectra of the cobalt(II) and copper(II)-cobalt(II) derivatives. Such studies indicate that the coordinated residues are maintained although there is evidence of some flexibility of the donor groups. The coordination around copper is slightly more tetragonal. Azide binding to the copper ion does not cause the complete detachment of one of the histidines from the copper coordination sphere, as happens with the untreated enzyme. PMID- 2919885 TI - Decreased activity of the pyruvate translocator and changes in the lipid composition in heart mitochondria from hypothyroid rats. AB - A study of the transport of pyruvate in heart mitochondria from normal and hypothyroid rats has been carried out. Heart mitochondria from hypothyroid rats translocate pyruvate via the alpha-cyanocinnamate sensitive carrier much more slowly than do mitochondria from normal rats. Kinetic analysis of the pyruvate transport shows that the Vmax of this process is decreased while there is practically no change in the Km values. Neither a decrease in the transmembrane delta pH value nor a decrease in the total number of the pyruvate carrier molecules, titrated with labeled alpha-cyanocinnamate, account for the decreased rate of pyruvate transport. The lower activity of the pyruvate translocator in mitochondria from hypothyroid rats is associated with a parallel decrease of the rate of pyruvate supported oxygen uptake. There is, however, no difference in either the respiratory control ratios or in the ADP/O ratios between these two types of mitochondria. The heart mitochondrial lipid composition is significantly altered in hypothyroid rats. Cardiolipin, particularly, was found to decrease by around 36%. In addition the pattern of fatty acids was found to be altered in mitochondrial membranes from hypothyroid rats. It is suggested that the decreased activity of the pyruvate translocator in heart mitochondria from hypothyroid rats can be ascribed to changes in the lipid environment which surrounds the pyruvate carrier molecule in the mitochondrial membrane. PMID- 2919886 TI - Generation of hydrogen peroxide by brain mitochondria: the effect of reoxygenation following postdecapitative ischemia. AB - The hypothesis that mitochondria damaged during complete cerebral ischemia generate increased amounts of superoxide anion radical and hydrogen peroxide (H2O2) upon postischemic reoxygenation has been tested. In rat brain mitochondria, succinate supported H2O2 generation, whereas NADH-linked substrates, malate plus glutamate, did so only in the presence of respiratory chain inhibitors. Succinate-supported H2O2 generation was diminished by rotenone and the uncoupler carbonyl cyanide m-chlorphenylhydrazone and enhanced by antimycin A and increased oxygen tensions. When maximally reduced, the NADH dehydrogenase and the ubiquinone-cytochrome b regions of the electron transport chain are sources of H2O2. These studies suggest that a significant portion of H2O2 generation in brain mitochondria proceeds via the transfer of reducing equivalents from ubiquinone to the NADH dehydrogenase portion of the electron transport chain. Succinate-supported H2O2 generation by mitochondria isolated from rat brain exposed to 15 min of postdecapitative ischemia was 90% lower than that of control preparations. The effect of varying oxygen tensions on H2O2 generation by postischemic mitochondrial preparations was negligible compared with the increased H2O2 generation measured in control preparations. Comparison of the effects of respiratory chain inhibitors and oxygen tension on succinate supported H2O2 generation suggests that the ability for reversed electron transfer is impaired during ischemia. These data do not support the hypothesis that mitochondrial free radical generation increases during postischemic reoxygenation. PMID- 2919887 TI - Purification of phospholamban from bovine cardiac muscle with organic solvents. AB - Phospholamban (PLB), an integral membrane protein of cardiac sarcoplasmic reticulum, was extracted from bovine cardiac muscle with an acidic chloroform/methanol mixture. A combination of gel permeation and ion-exchange chromatographies in organic solvents allowed the purification of PLB. The intensive use of organic solvents throughout the isolation yielded a highly purified and intact protein that can be phosphorylated by cAMP protein kinase. The ease of purification and the high yield obtained (2.5 mg/100 g of fresh tissue) show that organic solvents can be very useful in the extraction and purification of hydrophobic membrane proteins. PMID- 2919888 TI - Stereoselective ligand interactions of chicken liver phosphoenolpyruvate carboxykinase with fluorophosphoenolpyruvate. AB - The stereospecific interactions of chicken liver phosphoenolpyruvate carboxykinase (P-enolpyruvate carboxykinase) with the two geometric isomers of 3 fluorophosphoenolpyruvate (F-P-enolpyruvate) were examined. Previous studies have shown that the Z isomer of F-P-enolpyruvate is a substrate for P-enolpyruvate carboxykinase but the E isomer is a competitive inhibitor [T. H. Duffy and T. Nowak (1984) Biochemistry 23, 661-670]. The reasons for this substrate selectivity were investigated. Studies of the 1H, 19F, and 31P relaxation rates of the ligands in the binary Mn-ligand complexes indicate the formation of direct coordination complexes. The temperature and frequency dependence of the proton relaxation rates (PRR) of the respective enzyme-Mn-ligand complexes demonstrates that the perturbation of the electronic environment at the Mn(II) site on the enzyme is different upon binding of the inhibitor (E-F-P-enolpyruvate) in contrast to the binding of substrates (P-enolpyruvate or Z-F-P-enolpyruvate). Structural studies demonstrate that Z-F-P-enolpyruvate forms a second sphere coordination complex with enzyme-bound Mn(II). E-F-P-enolpyruvate exchanges slowly from the ternary complex and binds less than or equal to 10 A from the bound Mn(II). CD studies in the far-uv region demonstrate that the alpha-helical content of P-enolpyruvate carboxykinase is increased at the expense of antiparallel and parallel beta-sheet structure upon binding of Mn(II) and substrate (P-enolpyruvate or Z-F-P-enolpyruvate) to the apoenzyme, but show no such structural change upon binding of Mn(II) and E-F-P-enolpyruvate. Analogous results are observed from CD studies at the aromatic amino acid region (250-350 nm). The stereoselective catalytic activities of P-enolpyruvate carboxykinase with F-P-enolpyruvate analogs can be explained by different interactions of these ligands within the catalytic site of the enzyme. PMID- 2919889 TI - Monoclonal antibody-directed characterization of rat hepatic P450 catalyzing the omega-1 and omega-2 hydroxylation of prostaglandins. AB - Previous studies have demonstrated that methylcholanthrene (MC) treatment of rats increases 10-fold the omega-2 hydroxylation of prostaglandin E2 (PGE2) by liver microsomes (K. A. Holm, R. J. Engell, and D. Kupfer (1985) Arch. Biochem. Biophys. 237, 477-489). The current study identifies the cytochrome P450 form, which catalyzes a major portion of the omega-2 hydroxylation of prostaglandins in liver microsomes of MC-treated rats (MC-microsomes) and examines whether the same enzyme catalyzes this reaction in microsomes from untreated rats (control microsomes). Three monoclonal antibodies (MAbs), MC 1-7-1, 1-31-2, and 1-36-1, raised against the major liver P450 from MC-treated rats were used. MAb 1-7-1 binds P450(57K) and P450(56K) (P450c and P450d, respectively); MAb 1-31-2 binds primarily P450(57K); and 1-36-1 binds solely P450(57k). MAb 1-7-1 inhibited omega 2 and omega-1 PGE2 hydroxylations in MC-microsomes by 70 and 45%, respectively. By contrast, MAb 1-31-2 and 1-36-1 were not inhibitory. MAb 1-7-1 did not inhibit PGE2 omega-2 hydroxylation in control or in microsomes from phenobarbital-treated rats (PB-microsomes). Since MAb 1-7-1 binds to both P450c and P450d, and 1-31-2 and 1-36-1 bind to P450c but are not inhibitory, these findings did not permit the determination of whether in MC microsomes a single isozyme (P450c or P450d) or both isozymes catalyze the omega-2 hydroxylation. This question was partially resolved by the observation that immunoaffinity-isolated P450c, supplemented with purified NADPH-P450 reductase, catalyzes effectively the omega-2 hydroxylation and to a lesser extent the omega-1 hydroxylation. There was no activity in the absence of reductase. The P450 antibody complex exhibits characteristics similar to those of the omega-2 hydroxylating activity in intact MC-microsomes supported by H2O2, by demonstrating a much higher activity when H2O2 is used instead of reductase and NADPH. Furthermore, a reconstituted monooxygenase composed of rat liver reductase and P450c, purified by conventional means, hydroxylated PGE2 at the omega-2 and omega-1 sites at a ratio of 2.8, similar to that obtained with the P450-antibody complex. These findings demonstrate that a major portion of the omega-2 hydroxylation of PGs in MC-microsomes is catalyzed by P450c; however, the possibility that some omega-2 hydroxylating activity is due to P450d was not ruled out.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2919890 TI - Structural and immunochemical analysis of three alpha-limit dextrin oligosaccharides. AB - Complete structures are described for three urinary oligodextrins from one patient with type II and one patient with type III glycogen storage disease. GLC MS, direct probe MS, and 1H NMR demonstrate two heptasaccharides and one hexasaccharide containing only alpha 1-4 and alpha 1-6 linkages. The observation that all three oligosaccharides were present in urine of both patients and the occurrence of alpha 1-4 and alpha 1-6 linkages in characteristic sequences indicates that the oligodextrins are limit dextrins derived from alpha-amylolytic degradation of glycogen. The binding affinities of the oligodextrins for a monoclonal antibody (401/6) raised against Glc alpha 1-6Glc alpha 1-4Glc alpha 1 4Glc, were determined by frontal analysis. The highest affinity was exhibited by Glc alpha 1-6Glc alpha 1-4Glc alpha 1-4Glc followed by the two heptasaccharides and the hexasaccharide. The results from quantitative affinity measurements agree with results of structural analysis by physical methods in that all oligodextrins containing the nonreducing terminal sequence, Glc alpha 1-6Glc alpha 1-4Glc . . . , are specifically bound by the antibody with similar affinities, but the affinity is somewhat higher for chains containing the tetrasaccharide sequence Glc alpha 1-6Glc alpha 1-4Glc alpha 1-4Glc at the nonreducing terminal. Utilization of affinity methods offers clear advantages for isolation and characterization of oligosaccharides with very similar structures. PMID- 2919891 TI - [Activation of neutrophil function by MDP-Lys(L 18)]. AB - The study was carried out to confirm the effect of MDP-Lys (L 18) on the neutrophil number and function in the patients with lung cancer. The patients were enrolled only in case of leukopenia (equal or less than 3,000/mm3 after anticancer chemotherapy) and subcutaneously given 200 mcg of MDP-Lys (L 18) for 7 days. Mean leukocyte counts were found to be 3,900/mm3 and 5,500/mm3 one day and one week after MDP-Lys (L 18) treatment, respectively. The rate of "markedly effective" and "effective" was 53% (8/15). Chemiluminescence by zymosan showed a significant increase after MDP-Lys (L 18) treatment. However, no change of neutrophil function was observed in the tests of chemiluminescence by phorbol myristate acetate, superoxide (O2-) production, hydrogen peroxide (H2O2) production, chemotaxis, bacterial killing and opsonization. Transient fever was observed in 6 cases and eruption accompanied with one fever case. It was concluded that MDP-Lys (L 18) could prevent infection in cancer-bearing immunocompromised patients by increasing the neutrophil number and function. PMID- 2919892 TI - [Combination chemo-endocrine therapy of metastatic and stage IV breast cancer with cyclophosphamide, adriamycin, prednisolone and tamoxifen (CAPT)--with special reference to management of brain and liver metastasis]. AB - Sixty-three evaluable patients with metastatic and stage IV breast cancer who had not previously undergone chemo-endocrine therapy were treated with a combination chemoendocrine therapy regimen consisting of cyclophosphamide 100 mg p.o. every day, adriamycin 10 mg i.v. on day 1 to 5, prednisolone 10 mg or 20 mg (20 mg was given on day 1 to 5) p.o. every day, and tamoxifen 20 mg p.o. every day. Adriamycin on day 1 to 5 was repeated three times every two weeks. After a total dose of 150 mg of adriamycin, the patients were changed to maintenance therapy consisting of cyclophosphamide 100 mg p.o., prednisolone 10 mg p.o. and tamoxifen 20 mg p.o. every day. After 72 months of the treatment there were 61 patients good for evaluation, 13 patients achieved a complete response (21.3%) with a median survival of 30.5 months and 18 patients had a partial response (29.5%) with a median survival of 21.0 months, and 30 patients failed to respond (49.2%) with a median survival of 8.5 months. There was a significant difference in survival time between responders (CR + PR) and non-responders (NC + PD) (p less than 0.001). Responses by site were seen in lung 10/18 (55.6%), liver 3/6 (50.0%), brain 2/4 (50.0%), bone 6/17 (35.3%) and soft tissue 14/24 (56.3%). A Satisfactory response for brain and liver metastasis, which are usually viewed as a sign of grim prognosis, was obtained similar to other sites of metastasis. Retreatment with CAPT, which was attempted in patients with secondary brain metastasis who responded to CAPT for initial brain metastasis, was uniformly effective. High ration of androgen to corticosteroid, positive estrogen receptors, long disease-free survival (over two years), premenopausal, high Broca' index (above 110) resulted from the chemo-endocrine therapy regimen CAPT. Toxicity was minimal and consisted of nausea, vomiting, alopecia and leucopenia. PMID- 2919893 TI - [Circumvention of ACNU-resistance in rat glioma cells by pretreatment with O6 methylguanine]. AB - The chemotherapy of malignant brain tumors has been, only partially successful yet. Recently major concern is drug resistance, one of possible mechanisms of such drug resistance stems from inducible repair enzyme, especially in case of chloroethylnitrosoureas as ACNU or BCNU. We examined the changes of acquired resistance to ACNU in rat glioma cells by pretreatment with O6-methylguanine, which is a substrate for O6-methylguanine methyltransferase. ACNU-resistant (9L/AC) cells had established after 10 times treatments of ACNU. 9L/AC cells were pretreated with 2 mM O6-methylguanine for 2 hours, and subsequently challenged with increasing doses of ACNU for 2 hours. In vitro colony formation assay the survival fraction of 9L and 9L/AC cells ranged from 0.39 to 0.63 by 2-hour reaction of 1-3 mM O6-methylguanine. Based on the dose-response curve for ACNU in 9L/AC cells, by O6-methylguanine pretreatment (2 mM), ACNU-resistance decreased markedly to one-third, one-fifth, and one-two hundredth at 12, 24, 36 microM ACNU, respectively. In contrast, the survival of 9L cells against ACNU was similar under O6-methylguanine pretreatment or nontreatment condition. Therefore, ACNU-resistance is considerably related to DNA repair enzyme induction, and the substrates may potentiate the cell-killing effect of ACNU in the resistant glioma cells. PMID- 2919894 TI - [Efficacy of etoposide in bone metastasis of breast cancer]. AB - We have used ADM, MMC, CDDP and other drugs for a case of bone metastasis of breast cancer, but the bone destruction was advanced and she could not walk. We have also used etoposide, a new chemotherapeutic drug, for the same case. Two months later bone sclerosis was seen by X-ray film and pain disappeared. Bone sclerosis then advanced after 6 months, she has begun to stand, and after 8 months she has been able to walk with a cane. There was no severe side effect. Etoposide was very effective for bone metastasis of the breast cancer. PMID- 2919895 TI - Side gland of Suncus murinus as a new model of sebaceous gland: 5 alpha reductase, androgen receptor, and nuclear androgen content in male and female animals. AB - The side gland of Suncus murinus is composed of well-developed sebaceous glands in both males and females. We measured the 5 alpha-reductase activity, androgen receptor content, and the intranuclear concentrations of testosterone and dihydrotestosterone in this side gland taking it as a new experimental model of human sebaceous glands. Lineweaver-Burk plot analysis suggested the presence of two classes of 5 alpha-reductase with different Km for testosterone in the homogenate. The enzyme activity was slightly higher in males than in females in the presence of a high concentration of testosterone. The levels of androgen receptors were approximately 40 and 30 fmol/mg protein in the cytosol and nuclei, respectively. The values did not differ significantly between males and females. The intranuclear concentration of dihydrotestosterone in the side gland was higher than that of testosterone in each sex. The intranuclear level of each of these two androgens in the female side gland was comparable to that in the male side gland despite the fact that the serum level of testosterone was much lower in the female. These data clearly indicate that the side gland is a typical target tissue for androgens in the female as well as in the male. Androgens other than testosterone may serve as precursors of dihydrotestosterone in the female side gland. PMID- 2919896 TI - Normal IgA production by peripheral blood lymphocytes in dermatitis herpetiformis and linear IgA dermatosis. PMID- 2919897 TI - Decreased levels of vitamin A in serum of patients with psoriasis. PMID- 2919898 TI - Human immunodeficiency virus and the patient who needs a cardiac operation. PMID- 2919899 TI - Human immunodeficiency virus and the cardiac surgeon: a survey of attitudes. AB - The decision to operate on carriers of the human immunodeficiency virus (HIV) who need an urgent cardiac operation is difficult. There is a lack of knowledge about the effect of the presence of HIV on operative risk, about the effect of cardiopulmonary bypass on the progression of HIV infection to acquired immunodeficiency syndrome (AIDS), and about the risk to the cardiac surgical team of operating on 1 or more HIV carriers. This lack of knowledge is exacerbated by the strict regulations surrounding testing. We polled the board-certified cardiac surgeons in the United States on their willingness to perform open cardiac procedures on HIV carriers and AIDS patients. Fifty-three percent of the surgeons responded. Two thirds of them will operate on HIV carriers who need an urgent cardiac operation but regard the presence of AIDS as a contraindication to cardiopulmonary bypass. This is presumably a medical judgment. Those who will not operate on HIV carriers are apparently motivated by fear rather than moral judgments concerning the patients. Virtually all surgeons want to be able to test "high-risk" patients, and a substantial majority would test all patients. PMID- 2919900 TI - Reperfusion injury in the lung preserved for 24 hours. AB - The left lower lobes of 28 canine lungs were isolated, preserved, and then reperfused for 150 minutes. Five groups of lobes were studied: group 1, control (n = 5); group 2, one hour of warm ischemia (n = 5); group 3, one hour of warm ischemia + oxygen free radical scavengers (n = 5); group 4, 24 hours of cold ischemia (n = 8); and group 5, 24 hours of cold ischemia + oxygen free radical scavengers (n = 5). Oxygen free radical scavengers consisted of superoxide dismutase and catalase (100 micrograms/mL) given at the moment of reflow. Extravascular lung water (grams per gram of blood-free dry lobe weight) after reperfusion was 2.75 +/- 0.19, 5.46 +/- 0.60, 4.08 +/- 0.37, 9.43 +/- 0.98, and 6.91 +/- 0.95 for groups 1 through 5, respectively (p less than 0.05, groups 2 through 5 versus group 1; p less than 0.05, group 2 versus group 3 and group 4 versus group 5). Lung tissue lipid peroxidation, measured as thiobarbituric acid reactive material, was 117 +/- 14, 314 +/- 19, and 163 +/- 25 nmol/g dry lobe weight for groups 1, 4, and 5, respectively (p less than 0.05, group 4 versus group 1 and group 4 versus group 5). The data suggest that oxygen free radical scavengers attenuate reperfusion injury after long-term hypothermic lung preservation. PMID- 2919901 TI - In situ prosthetic graft replacement for mycotic aneurysm of the aorta. AB - Mycotic aneurysms as defined in this study include only those naturally occurring aortic aneurysms that result from or are secondarily infected by bacteria arising in a distant site of infection. Of the 2,585 patients treated for aortic aneurysm during the past 8 1/2 years, 22 patients had disease conforming to this definition. The aneurysms were located in the ascending aorta in 2 patients, ascending aorta and arch in 5, arch and descending aorta in 1, descending thoracic aorta in 1, separate descending and abdominal aorta in 1, thoracoabdominal aorta in 5, upper abdominal aorta in 6, and infrarenal abdominal aorta in 1. The primary source of infection was the urinary tract in 2 patients, salmonellosis in 4, pneumonia in 3, sub-acute bacterial endocarditis in 2, ear, nose, and throat in 2, cellulitis of the hand in 1, chronic wounds in 2, dental extraction in 1, lumbar disc space infection in 1, septic thrombophlebitis in 1, and generalized febrile illness in 3. The duration of febrile illness ranged from 2 weeks to 1 year. All patients were treated with antibiotics and operation was performed within 24 hours after admission in 11 patients and within one to eight days after admission in 11. Treatment consisted of in situ graft replacement. Appropriate antibiotics were given intravenously for 4 to 6 weeks in patients with positive cultures and continued orally for the rest of the patients' lives. Of the 22 patients, 19 (86%) were early survivors, and all are still alive 3 months to 8 years postoperatively. Only 1 had a recurrent infection, which involved the intervertebral disc space. PMID- 2919902 TI - Pneumothorax in cystic fibrosis: a 26-year experience. AB - We reviewed the records of all patients with cystic fibrosis and radiologically demonstrated pneumothorax at Rainbow Babies and Childrens Hospital between 1959 and 1987. There occurred 144 pneumothoraces, 71 right and 73 left, in 99 patients, 48 female and 51 male. The median survival from the date of the first pneumothorax was 29.9 months. Primary therapy included the following: observation; tube thoracostomy; tube thoracostomy with instillation of quinacrine hydrochloride, tetracycline, silver nitrate, or talc; or partial pleurectomy. Complications were minimal in each group. The surgical group did significantly better than all other groups except the group given talc. We conclude that pneumothorax is a late and ominous complication of cystic fibrosis. The primary treatment of pneumothorax should be partial pleurectomy. Talc instillation should be reserved for patients in respiratory failure who are too ill to undergo operation and for the occasional patient in whom surgical intervention fails. PMID- 2919903 TI - Cryopreservation of canine trachea: functional and histological changes. AB - The purpose of this study was to evaluate tracheal viability and to document histological changes in an autograft implanted in the abdominal wall after a 1 week period of cryopreservation. A 5-cm segment of cervical trachea was resected in 6 dogs. One-half of the segment was cryopreserved and stored in liquid nitrogen at -196 degrees C for 1 week. The other half was immediately implanted in an abdominal pouch fashioned from the rectus abdominis muscle (control). One week later, the cryopreserved segment was thawed and then implanted in a similar contralateral muscular pouch. Five weeks later, the control and cryopreserved autografts were removed and compared with the in situ trachea. Ciliary beat frequency was assessed by transmitted light technique. Histology was evaluated by light microscopy. Gross anatomy and mucus production were maintained after cryopreservation. Histologically the cryopreserved segment displayed both normal epithelium and smooth muscle cells, but the cartilage was abnormal as characterized by empty lacunae. Mean ciliary beat frequency of in situ, control, and cryopreserved segments was 13.3 +/- 1.8, 13.5 +/- 1.5, and 13.3 +/- 1.1 beats per second (+/- the standard deviation), respectively. We conclude that smooth muscle, epithelium with mucus production, and ciliary function were retained after cryopreservation and reimplantation. Histological changes, however, were suggestive of early cartilage ischemia. These findings support further evaluation of cryopreserved canine tracheal grafts. PMID- 2919904 TI - Long-term results in neonates with pulmonary atresia and intact ventricular septum. AB - Our entire institutional experience with pulmonary atresia and intact ventricular septum (1965 through 1987) included 115 patients, 16 of whom died before surgical intervention. Fifty-six percent of surgical patients (n = 99) had angiographic evidence of right ventricle-coronary arterial connections. The early mortality in the surgical group was 27.2%, and the actuarial survival was 24.7% +/- 6% at 13 years postoperatively. Multivariate analysis indicated that the presence of ventriculocoronary connections (p = 0.037), a decreasing ratio between right ventricular and left ventricular pressure at the initial cardiac catheterization (p = 0.007), and lower weight at operation (p = 0.001) were incremental risk factors for postoperative death; the presence of Ebstein's anomaly was an additional risk factor in the overall experience (including patients not surgically treated) (p = 0.01). Nearly all long-term survivors underwent at least one reoperation, including right ventricular outflow tract reconstruction (n = 39) and thromboexclusion of the right ventricle (n = 9). The presence of severe stenosis or interruption of the proximal left anterior descending coronary artery system was a uniformly lethal risk factor for patients undergoing these procedures (p = 0.0003). We conclude that surgical procedures that successfully decompress the right ventricle will usually result in biventricular circulation in and long-term survival of patients with pulmonary atresia with intact ventricular septum not complicated by Ebstein's anomaly or extensive ventriculocoronary connections. Decompression or thromboexclusion of the right ventricle is contraindicated in patients with ventriculocoronary connections and a right ventricle-dependent coronary circulation. PMID- 2919905 TI - Ten years' experience with the Senning operation for transposition of the great arteries: physiological results and late follow-up. AB - We report our results in 93 consecutive infants and children who underwent atrial repair of simple transposition of the great arteries using the Senning operation between February 1978 and February 1988. Mean age at operation was 5.6 +/- 6.3 months (range, 1 week to 4 years); 60 were less than 6 months old. There were 65 boys and 28 girls. Operative mortality was 5.4%, and there has been 1 late death. Average follow-up is 45.1 months with 39 followed more than 3 years and 25 followed more than 5 years. Postoperative cardiac catheterization was performed in 43 patients. Right ventricular ejection fraction at rest averaged 0.50 +/- 0.09 and was normal in 26 patients. Response of right ventricular ejection fraction to afterload stress was abnormal in 12 of 14 patients tested. Right ventricular ejection fraction increased normally during exercise in 6 patients, but was abnormal in 15. Mild tricuspid regurgitation was noted in 10 patients. Mild obstruction of the superior vena cava was noted in 4 patients. Baffle leak requiring reoperation occurred in 1 patient. Seventy-two of 80 patients are in sinus rhythm by latest electrocardiogram. Postoperative electrophysiological studies were performed in 34 patients and Holter monitoring was performed in 22. A major arrhythmia occurred in 8 patients: 3 required a pacemaker for junctional rhythm or sinus node dysfunction, 2 have symptomatic or inducible supraventricular tachycardia, 2 have junctional rhythm, and 1 has sick sinus syndrome. Eight additional patients have delayed sinus node recovery time. At last follow-up, 78 children (97.5%) are in New York Heart Association functional class I, and 2 (2.5%) are in class II.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2919906 TI - Continued assessment of the combined Collis-Nissen operation. AB - The combined Collis-Nissen operation has been performed in 353 patients. Forty five percent had reflux esophagitis without stricture; 20%, peptic stricture; 72%, a sliding hiatal hernia; 17%, a paraesophageal hernia; 21%, previous antireflux operation; 15%, esophageal spasm; 8%, scleroderma; and 32%, marked obesity. There were 4 postoperative deaths (mortality rate, 1.1%). Complications occurred in 28 patients (8%) and included wound infection (2.2%), esophageal or gastroplasty tube leak (1.7%), bleeding (1.1%), splenic injury, gastric atony, and crural repair dehiscence (each less than 1%). Follow-up includes personal interview, esophageal manometry, and standard acid reflux testing. The average length of follow-up for 261 patients (74%) followed at least 12 months is 43.8 months. Fifty-eight percent have been followed at least 36 months; 41%, 48 months; and 29%, 60 months or longer. Subjectively, in these 261 patients, reflux has been eliminated in 75%, is mild in 11%, is moderate in 9%, and is severe in 5%. Eight percent have postthoracotomy pain; 3%, early satiety ("bloats"); and 1%, postvagotomy diarrhea. Seventeen percent require either periodic or regular esophageal dilations for dysphagia. Objectively, intraesophageal pH studies show good reflux control in 91% and poor reflux control in 9%. Twenty-six patients (10%) have required reoperation for recurrent reflux or dysphagia. These results substantiate satisfactory reflux control using the Collis-Nissen operation in patients at risk for recurrence after standard repairs, but also emphasize that, like other antireflux procedures, the Collis-Nissen operation is not without some degree of postoperative adverse symptoms. PMID- 2919907 TI - Closure of chronic postpneumonectomy bronchopleural fistula using the transsternal transpericardial approach. AB - Thirteen patients with postpneumonectomy bronchopleural fistula occurring 4 months to 10 years after the initial operation have been treated with a transsternal transpericardial approach after the associated empyema had been treated by either tube thoracostomy or open-window thoracostomy. In 10 patients, there were contraindications to using an ipsilateral transthoracic approach. In 10 of the 13 patients, the procedure was successful. Three fistulas recurred; two were quite small, one of them closing spontaneously within 6 months. There were no deaths or clinically significant morbidity related to the transsternal approach. We have found this technique to be most applicable in those patients in whom other procedures have failed to resolve the problem. The technique is relatively simple and safe. PMID- 2919908 TI - Clinical and hemodynamic results after mitral valve replacement in patients with obstructive hypertrophic cardiomyopathy. AB - Mitral valve replacement has been performed in patients with obstructive hypertrophic cardiomyopathy if: (1) the interventricular septum is smaller than 18 mm in the region of usual resection; (2) atypical septal morphology is encountered; (3) a previous left ventricular myomectomy has been performed but residual major obstruction and symptoms persist; or (4) intrinsic mitral valve disease exists. Since 1983, mitral valve replacement has been performed in 58 patients with obstructive HCM only. Thirty-three female patients (mean age, 47.9 years) and 25 men (mean age, 45.7 years) met criteria 1 through 3 for mitral valve replacement. Patients with intrinsic mitral valve disease (criterion 4) were omitted from this study. All patients were in New York Heart Association functional class III or IV and had failed optimal medical therapy. Low-profile mechanical prostheses and bioprostheses were implanted, and the early mortality (less than 30 days or in the hospital) was 8.6% (5/58). Six patients (11.3%) died late, 3 suddenly of probably arrhythmia, 2 of respiratory failure, and 1 of an anticoagulant-related complication. After mitral valve replacement, 40 (83%) of 48 patients surviving operation and returning for evaluation were in functional class I or II, whereas 8 patients were in functional class III. Hemodynamic data obtained 6 months postoperatively showed that pulmonary artery wedge pressure was normal (13.7 +/- 4 mm Hg [+/- standard deviation]), left ventricular end diastolic pressure had decreased (10.9 +/- 3.4 mm Hg), cardiac index was maintained (2.6 +/- 0.6 L/min/m2), and resting and provoked gradients were unremarkable. Mean follow-up was 24.2 months, actuarial survival was 86% at 3 years, and survival free from thromboembolism, anticoagulant-related complication, reoperation, and congestive heart failure for the same interval was 68%. Complications such as ventricular septal defect and complete heart block are avoided in patients undergoing mitral valve replacement, but device-related and cardiac-related complications can add to the morbidity and mortality in these patients in the long term. PMID- 2919909 TI - Penetrating wounds to the heart: a wartime experience. AB - Forty-nine war casualties with penetrating cardiac wounds were treated at the Hotel-Dieu de France University Hospital between April 1975 and December 1987. All the wounds were caused by high-velocity missiles. An aggressive approach was utilized. Emergency room thoracotomy was performed in 17 "lifeless" patients, 4 of whom survived. Twenty-seven of the 32 patients who were in stable enough condition to undergo initial repair in the operating room survived. Overall survival was 63% (31/49). No intracardiac injuries were diagnosed in survivors, and no cardiac reoperations were required. Careful analysis of the trajectory of the missile or missiles and a portable chest roentgenogram were the most important factors for diagnosing a penetrating wound to the heart and for predicting potential associated injuries. PMID- 2919911 TI - Delayed primary closure after sternal wound infection. AB - Infected median sternotomy is a major complication of cardiac operations. Over a 30-month period, 25 sternal wound infections were treated at a single institution. Twenty-four (2.7%) followed 883 operations with cardiopulmonary bypass, and 1 followed median sternotomy for a noncardiac procedure. Twenty-one of the 25 patients survived to sternal closure. Eighteen patients were treated with delayed primary closure and 3 with pectoralis muscle flaps. Fifteen patients (83%) had an uneventful postoperative course after delayed primary closure. In 2 patients reoperation was required for sternal dehiscence, and in 1 patient a superficial wound infection developed, which was treated with local wound care. In all 18 patients the sternum eventually healed. Criteria for delayed primary closure included clean tissue surfaces without purulent debris, the absence of pockets of purulent drainage, and negative wound cultures obtained 24 hours before closure. The average time from operation to sternal incision and drainage was 11 days (range, five to 59 days). Delayed primary closure was performed nine days after incision and drainage (range, five to 27 days). The average hospital stay was 24 days after sternal incision and drainage (range, nine to 85 days). Cultures from specimens taken at the time of sternal incision and drainage were positive in all patients. Wound cultures were positive at the time of sternal closure in 5 patients. Wound complications developed in 2 of these 5 patients. Delayed primary closure has many of the advantages of classic methods, but fewer complications. Results are comparable, while allowing simpler wound care and less cosmetic deformity. Delayed primary closure is an acceptable alternative in the treatment of sternal wound infections. PMID- 2919910 TI - Cryosurgical ablation of accessory atrioventricular pathways without cardiopulmonary bypass: an epicardial approach for Wolff-Parkinson-White syndrome. AB - An epicardial approach has been developed and applied to 31 Kent bundles (23 parietal, 1 right anteroseptal, and 7 posteroseptal bundles) in 28 patients with Wolff-Parkinson-White syndrome. Our technique consists of dissection of the atrioventricular fat pad of the Kent bundle site using an ultrasonic aspirator and subsequent cryosurgical ablation. For the left parietal and posteroseptal pathways, the apex of the heart has to be retracted upward, but this maneuver was well tolerated in all patients. Moreover, even through a narrow operative field, the ultrasonic aspirator permitted deliberate dissection on the beating heart without injury to major coronary vessels or the atrial wall. In 89% of the patients, operation was performed without the use of heart-lung bypass. All patients were free from preexcitation. With this technique, all Kent bundles except that adjacent to the atrioventricular node can be ablated on the beating heart, usually without heart-lung bypass. PMID- 2919912 TI - Neonatal pneumopericardium with high-frequency ventilation. AB - Pneumopericardium is an uncommon condition in the neonate and has not, to our knowledge, previously been reported in patients treated with high-frequency ventilation. The results of such treatment in 8 neonates seen in the Neonatal Intensive Care Unit, Wilford Hall USAF Medical Center, San Antonio, Texas, are presented. The mean gestational age was 35 weeks, and birth weight averaged 2.7 kg. The pneumopericardium developed while the patients were on high-frequency ventilation, and the diagnosis was confirmed with a chest radiogram. Treatment included pericardiocentesis with a needle catheter followed by placement of a 10F to 14F chest tube into the pericardial space. The pneumopericardium resolved in all 8 patients. Three of the newborns died of underlying disease; 5 survived and were discharged from the hospital. Pneumopericardium in the neonate is a life threatening complication, and appropriate therapy includes drainage with a pericardial tube placed under direct vision. PMID- 2919913 TI - Aortic allografts: reconstruction of right ventricle-pulmonary artery continuity. AB - The use of aortic allografts in the repair of congenital cardiac lesions has increased as a result of both the advent of cryopreservation and the effects of increased donor availability secondary to infant transplantation. During the period 1986 through 1987, 38 cryopreserved aortic allografts were placed for right ventricle-pulmonary artery discontinuity. Size of the allografts ranged from 11 to 26 mm (mean size, 19 mm), and age of the patients ranged from 6 weeks to 26 years (mean age, 5 years). Twenty-one patients had primary placement of aortic allografts, and 17 underwent replacement of previous conduits. There were 5 hospital deaths (13%) overall, only 1 among the 10 patients younger than 6 months of age with truncus arteriosus, and none among the 17 patients having conduit replacement. A large conduit could be placed with a low incidence (10.5%) of postoperative hemorrhage related to the conduit. The aortic allograft is our conduit of choice for both conduit replacement and primary repair of right ventricle-pulmonary artery discontinuity. PMID- 2919914 TI - Diagnosis of traumatic thoracic aortic rupture: a 10-year retrospective analysis. AB - A 10-year retrospective analysis of 82 patients with suspected thoracic aortic rupture (TAR) due to blunt chest trauma was performed to define which symptoms and signs were helpful in making an early diagnosis. Symptoms and signs associated with TAR included midscapular back pain (in the absence of thoracic spine fracture), unexplained hypotension, upper extremity hypertension, bilateral femoral pulse deficits, and initial chest tube output in excess of 750 mL. Chest roentgenographic signs seen with significantly greater frequency in the 12 patients with TAR than in 70 patients without such rupture included a widened paratracheal stripe (7 patients), deviation of the nasogastric tube or central venous pressure line (5 patients), blurring of the aortic knob (9 patients), abnormal paraspinous stripe (6 patients), and rightward tracheal deviation (5 patients). Mediastinal widening of greater than 8 cm occurred in 11 of the 12 patients with TAR (sensitivity, 92%); its specificity, however, was only 10% (11 true-positive and 63 false-positive results). In patients in hemodynamically stable condition who display these findings, immediate aortography should be considered. The presence of myocardial contusions, intraabdominal injuries, and pelvic fractures also occurred more frequently in patients with TAR. We conclude that a detailed history, physical examination, and chest roentgenography, with rapid progression to aortography in suspicious cases, represent the safest and most reliable approach to patients with TAR. PMID- 2919915 TI - Effect of cold cardioplegic solution and hypothermia on response to acetylcholine in perfused epicardial coronary artery of pig. AB - The effect of cold cardioplegic solution and hypothermia on the response to acetylcholine, a major postganglionic neurotransmitter of the parasympathetic nervous system, was studied using perfused epicardial coronary arteries of pigs. Cold crystalloid cardioplegic solution (5 degrees C) and hypothermia including topical cooling with slushed ice significantly augmented the coronary flow reduction by acetylcholine at one and two hours after rewarming. Cold Krebs Henseleit solution (5 degrees C) with hypothermia showed similar effects. However, cardioplegic solution at 37 degrees C did not affect the responsiveness. The coronary flow reduction induced by potassium chloride (60 mmol/L) did not change even after the administration of cold cardioplegic solution (5 degrees C) or cold Krebs-Henseleit solution (5 degrees C), indicating that cooling did not necessarily augment the coronary contractile response generally. It is concluded that cooling and subsequent rewarming can potentiate the contractile response of the coronary artery of the pig to acetylcholine. This suggests that cold cardioplegic solution with hypothermia can promote intraoperative coronary spasm upon activation of the parasympathetic nervous system. PMID- 2919916 TI - Prediction of post-cardiopulmonary bypass cardiac output. AB - The ability to predict cardiac output (CO) before termination of cardiopulmonary bypass (CPB) allows identification of potential complications once the patient is off bypass. We have previously demonstrated that CO early after CPB can be reliably predicted by a plot of venous oxygen saturation at various flow rates on CPB, based on in-line monitoring of venous oxygen saturation. In this study, we evaluated a simplified technique for predicting CO with a series of 50 patients on CPB. When CPB weaning began, patients were normothermic, anesthetized, and paralyzed. Venous oxygen saturation and arterial blood flow were recorded. At low pump flow just before termination of CPB, the final venous oxygen saturation was recorded. Assuming a proportional relationship between venous oxygen saturation and arterial blood flow, CO early after CPB was predicted. The simplified CO prediction was compared with the thermodilution CO immediately after CPB. The simplified technique reliably predicted CO early after CPB compared with the thermodilution technique. The simplicity and reliability increase the clinical value of the CO prediction. PMID- 2919917 TI - Homograft aortic root replacement to correct infective endocarditis requiring seven open cardiac procedures. AB - Infective endocarditis, presumably from a septic dental focus, affecting the aortic valve was seen as acute aortic regurgitation in a 20-year-old woman. Seven open cardiac procedures for replacement of the aortic valve and left ventricular outflow tract were performed over the subsequent 6 years. Aortic root replacement using a fresh antibiotic-sterilized homograft was performed as the last definitive operative procedure. This article is presented to highlight (1) the use of homograft aortic root replacement for extensive involvement of aortic valve and left ventricular outflow tract in cases of infective endocarditis and (2) the feasibility of multiple sternal reentries when indicated. PMID- 2919918 TI - Annuloplastic reconstruction for common atrioventricular valvular regurgitation in right isomerism. AB - Two patients who had common atrioventricular valvular regurgitation associated with right isomerism, univentricular heart of the right ventricular type, transposition of the great arteries, pulmonary stenosis, and both systemic and pulmonary venous anomalies underwent common atrioventricular valvular annuloplasty. They also underwent bilateral, bidirectional cavopulmonary shunt. A Carpentier's ring was used in patient 1 and a polytetrafluoroethylene tube was used in patient 2 to reduce the diameter of the common atrioventricular annuli. Postoperative catheterization confirmed complete elimination of regurgitation of the common atrioventricular valve in both patients. PMID- 2919919 TI - Pleuropulmonary actinomycosis associated with a systemic-to-pulmonary artery fistula and contralateral metastatic back mass. AB - We report a case of systemic-to-pulmonary artery fistula associated with thoracic actinomycosis and with metastatic hematogenous dissemination to the soft tissues of the back. The difficulty in diagnosing thoracic actinomycosis may predispose to the increased incidence of hematogenous spread of this disease. Although resection of pulmonary tissue including the infectious mass was required in previous cases, resection of the pleural mass alone was curative in this patient when combined with penicillin therapy. PMID- 2919920 TI - Vascular sling with tracheomalacia: surgical management. AB - Surgical repair of pulmonary artery sling without concomitant correction of associated tracheal abnormalities has yielded poor results in the past. We combined vascular sling repair done during cardiopulmonary bypass through a median sternotomy incision with tracheopexy for severe associated tracheomalacia in 2 infants. Neither experienced substantial postoperative respiratory difficulties and both had patent vascular anastomoses at 1 year after repair, thus supporting this approach when this combination of lesions is present. PMID- 2919921 TI - Transpericardial bronchial closure with omentopexy for postpneumonectomy bronchopleural fistula. AB - We report a case of successful closure of a postpneumonectomy bronchopleural fistula by means of the transpericardial approach with omentopexy through a median sternotomy incision. This method minimizes problems of infection, healing, and pulmonary function. PMID- 2919922 TI - Percutaneous endoscopic tracheostomy. AB - Bedside percutaneous tracheostomies are increasingly performed. This avoids patient transport to the operating room. Complications of this procedure are largely related to the blind nature of the technique. After laboratory studies, 4 patients underwent percutaneous endoscopic guided tracheostomy in a selective clinical trial. There were no procedure-related complications. Endoscopic guidance ensures precise low tracheostomy position, prevents paratracheal tube misplacement, and avoids inadvertent injuries. PMID- 2919923 TI - Cardioplegia delivery by combined aortic root and coronary sinus perfusion. AB - Retrograde coronary sinus perfusion for the administration of cardioplegic solutions has recently been the subject of renewed interest. A method is described for the administration of bolus antegrade cardioplegia followed by continuous retrograde coronary sinus perfusion, particularly for patients with left main artery disease, left main equivalent, or aortic root/aortic valve disease. Advantages of the technique are discussed, as well as its limitations and its use for myocardial preservation in heart transplantation. PMID- 2919924 TI - Left ventricular stress during extracorporeal membrane oxygenation. PMID- 2919925 TI - Muscle-sparing thoracotomy. PMID- 2919926 TI - Foreign body-induced hemoptysis. PMID- 2919927 TI - Right atrial cardioplegia: a safe procedure for myocardial protection. PMID- 2919928 TI - A simplified method for pleural abrasion. PMID- 2919929 TI - Preventing second-generation complications due to Staphylococcus aureus. PMID- 2919930 TI - Management of clinically suspected acute venous thrombosis in outpatients with serial impedance plethysmography in a community hospital setting. AB - The reported high sensitivity and specificity of impedance plethysmography (IPG) in the diagnosis of proximal vein thrombosis were evaluated in a prospective cohort follow-up study, in which IPG was performed three times over a period of seven days in 243 consecutive outpatients with clinically suspected deep venous thrombosis (DVT). The test was abnormal in 112 patients (46%). The positive predictive value of an abnormal IPG for venography-proved DVT was 90%. One hundred thirty-one patients (54%) with repeatedly normal tests were considered not to have DVT, and anticoagulants were withheld. During six months of follow up, completed in all patients with repeatedly normal IPG, no patient died of venous thromboembolism and no patient returned with clinically suspected pulmonary embolism. One patient (0.8%) returned after two months with recurrent leg symptoms, and venous thrombosis was documented (95% confidence limits, 0.02% to 4.21%). Another patient, who was nonsymptomatic, had an abnormal IPG at the three-month follow-up visit, and venography revealed venous thrombosis. Patients sent by general practitioners to a community hospital, with clinically suspected acute DVT, can be effectively managed by serial IPG alone. PMID- 2919931 TI - Short-course therapy for catheter-associated Staphylococcus aureus bacteremia. AB - To determine the efficacy of "short-course" therapy (less than 17 days) for Staphylococcus aureus catheter-associated bacteremia, 13 patients were prospectively followed up for at least three months after completion of therapy. A single patient relapsed after 28 days with endocarditis. No clinical or microbiological predictors of relapse could be identified, and coexistent medical conditions associated with some degree of immunosuppression did not appear to predispose to relapse. The results of this study and a review of the literature indicate that short-course therapy for uncomplicated S aureus catheter-associated bacteremia has a relapse rate of only 5% to 10% and, therefore, is reasonable therapy for this condition. The majority of relapses are endocarditis and occur within ten weeks after completion of therapy. Close follow-up during this period is essential. PMID- 2919932 TI - Changing physician test ordering in a university hospital. An intervention of physician participation, explicit criteria, and feedback. AB - To decrease inappropriate test ordering by medical house staff in a university hospital, we examined the feasibility of an intervention that involved physicians in developing explicit criteria for ordering four specific tests and incorporated feedback of tests ordered. We implemented a time series design with measures at 12 and six months before, during, and three weeks after the intervention. During the intervention, orders for initial or admission chest roentgenograms decreased by 22% and repeated orders for routine urinalyses, chest roentgenograms, and leukocyte differential counts decreased by 23%, 30%, and 46%, respectively, compared with the six-month preintervention period. Orders for prothrombin time and/or partial thromboplastin time did not fall. After the intervention, most test ordering remained at the intervention level. These preliminary results suggest that this intervention may be effective and not overly costly. PMID- 2919933 TI - Personal characteristics, career plans, and specialty choices of medical students elected to Alpha Omega Alpha. AB - Among US medical graduates in 1983, personal characteristics, career plans, and specialty choices of men and women elected to Alpha Omega Alpha (AOA), the honor medical society, differed in a number of ways from those of their non-AOA classmates. Students in AOA scored significantly higher on each subtest of the Medical College Admission Test, were disproportionately white, and had a higher proportion of parents achieving a post-high school education. Members of AOA participated in undergraduate medical research and authored papers during medical school significantly more frequently than those who were not members of AOA, planned a major career commitment to research, and planned careers in academic medicine significantly more frequently than those who did not belong to AOA. In contrast, neither religious preference, among students from Catholic, Jewish, or Protestant backgrounds, nor gender differentiated members of AOA from non-AOA members. Among the 15 specialties studied, internal medicine subspecialties and internal medicine attracted the highest proportion of students elected to AOA. PMID- 2919934 TI - Pulmonary disease in progressive systemic sclerosis. A complication of gastroesophageal reflux and occult aspiration? AB - Thirteen patients with progressive systemic sclerosis were studied to evaluate the possible role of gastroesophageal reflux as a contributing pathogenic factor in the pulmonary disease of the patients. The evaluation of all patients included fiberoptic esophagogastroduodenoscopy with biopsies of the esophagus, otolaryngologic evaluation, technetium Tc 99m sulfur colloid aspiration scan, pulmonary function testing, including the diffusing capacity for carbon monoxide (DLCO) test, and 24-hour intraesophageal pH monitoring with probes placed 5 and 15 cm above the lower esophageal sphincter. Eleven patients had microscopic and macroscopic evidence of proximal esophagitis, 12 patients had laryngeal changes suggestive of aspiration, and 12 patients had abnormal DLCO values. Using multiple regression analysis, the degree of DLCO impairment correlated with the proximal and distal reflux episodes and scores recorded by pH monitoring. There was direct and indirect evidence for proximal gastroesophageal reflux and aspiration in the majority of patients, and a distinct correlation between the severity of reflux and the severity of pulmonary disease. Aggressive antireflux therapy may be helpful in reducing the pulmonary damage due to aspiration in these patients. PMID- 2919935 TI - Fine-needle aspiration biopsy of the thyroid nodule. Results of a start-up project in a general teaching hospital setting. AB - The results of the initial 102 fine-needle aspiration biopsies of the thyroid performed at a 795-bed general teaching hospital are reported. Eighty-four of the nodules (82%) were cytologically benign, 18 nodules (18%) were suspicious, and none of the nodules was diagnosed as malignant. Five nodules In the suspicious group (28%) were found to be malignant following microscopic examination of the surgical specimens. There was one false-negative result. Based on the data from 21 patients with both cytologic and histologic diagnoses, the positive predictive value of this procedure was 38% and the negative predictive value was 87% (sensitivity, 83%; specificity, 47%). Our results were comparable with those of major referral centers. Guidelines for establishing a fine-needle aspiration biopsy program at a general hospital are suggested. PMID- 2919936 TI - Treatment of recurrent thyroid cysts by injection of tetracycline or minocycline. AB - We analyzed the effects of tetracycline hydrochloride or minocycline hydrochloride sclerotherapy on 66 recurrent thyroid cysts. All were hemorrhagic lesions except one serous cyst; cytologic study showed all were benign. On average, three treatments were given until resolution or the patient became unavailable for follow-up. The cumulative frequency of cyst disappearance was 33%, 45%, 52%, and 59% after 1, 2, 3, and 4 treatments. Five additional patients had cyst resolution after six to 19 treatments, and the serous lesion did not resolve. Cysts requiring more than two treatments were larger at presentation than those resolving after one or two treatments. Side effects in 179 treatments were local pain lasting ten to 20 minutes in 4.5%, radiated pain lasting one to two hours in 4.5%, fatigue lasting one to two days in 3.9%, and a febrile sensation lasting one to two days in 2.8%. Hemorrhagic thyroid cysts can usually be cured by repeated tetracycline or minocycline sclerotherapy with tolerable side effects. PMID- 2919937 TI - Reassessment of indications for digoxin. Are patients being withdrawn? AB - Several studies have shown that the majority of patients receiving digoxin can be successfully withdrawn. A medical record review was conducted to determine whether, in practice, patients were being withdrawn from digoxin. Original indications for digoxin therapy in 163 outpatients were as follows: congestive heart failure (CHF), 50%; supraventricular tachycardia (SVT), 23%; CHF and SVT, 10%; and unknown/unclear, 17%. One third of these patients were withdrawn during the 3.5-year study, and 79% remained stable, off digoxin. The most significant predictor of withdrawal was chart indication of reassessment of the need for digoxin. The majority of the patients (68%) were reassessed, and of these, almost half were withdrawn. Physicians appear to be reassessing the need for digoxin therapy, resulting in higher withdrawal rates than previously reported. Results suggest that patients with unclear original indications, a onetime indication, or without clinical evidence of CHF or SVT can be successfully withdrawn. PMID- 2919938 TI - Aerosol bronchodilator delivery methods. Relative impact on pulmonary function and cost of respiratory care. AB - Thirty-six acutely III, hospitalized patients with acute exacerbations of obstructive airway disease and a greater than 10% increase in forced expiratory volume in 1 s after administration of aerosolized bronchodilator were randomized to receive either metaproterenol sulfate delivered by updraft-compressor nebulization (UDN) or terbutaline sulfate delivered by metered-dose inhaler (MDI) with a spacer. Serial analyses of pulmonary function measurements were performed with the use of 95% confidence intervals for the percentage response ratios of MDI to UDN. The response to MDI was at least equivalent to that of UDN, and MDI use was associated with no prolongation of hospital stay. Equivalent bronchodilation was achieved with MDI therapy with a lower daily charge for therapy for each patient and less respiratory therapist time. In hospitalized bronchodilator-responsive patients with acute exacerbations of obstructive airway disease, the MDI/spacer combination is the preferred approach when the status of the patient allows its use. PMID- 2919939 TI - Heterosexual human immunodeficiency virus transmission among the middle class. AB - Patterns of heterosexual human immunodeficiency virus (HIV) spread among the middle class have not been previously reported. Thirty-nine (35 women and four men) heterosexual contacts of HIV-infected individuals were evaluated by a private infectious diseases practice located in a predominantly white middle class borough of New York City. Thirty-five of 39 patients were white. The mean household income of all patients was +41,200. Source cases (28 men and four women) were predominantly intravenous drug abusers (IVDAs). After excluding those contacts who were referred because of HIV or hepatitis B virus infection, six of 27 women and one of three men who agreed to be tested were seropositive for HIV. Heterosexual HIV spread is occurring among the middle class, with the predominant sources being IVDAs who do not fit the stereotype of being minorities and lower class. Condoms were not regularly utilized in these relationships even though (1) 23 of 32 contacts became aware of their partners' risk behaviors before the diagnosis of HIV infection, and (2) 23 of 32 IVDAs had attended a methadone program. Such programs could be better utilized to provide HIV-related education since they provide access to many of these IVDAs. PMID- 2919940 TI - Acute hyperparathyroidism with systemic calcinosis. Report of a case. AB - A patient with a huge mediastinal parathyroid adenoma had an acute hypercalcemic crisis. The patient exemplifies the many pitfalls in diagnosis and management of this unusual complication. Postoperatively the patient further developed severe calciphylaxis with calcinosis cutis and systemic and pulmonary calcinosis, a most rare condition. PMID- 2919941 TI - Toxicity of methotrexate compared with azathioprine in the treatment of rheumatoid arthritis. A case-control study of 131 patients. AB - One hundred thirty-one patients with rheumatoid arthritis treated with either azathioprine sodium (n = 37, 102.7 +/- 32.9 mg/d) or methotrexate sodium (n = 94, 8.4 +/- 3.0 mg/wk) were followed up for 38 +/- 23.3 months to determine the nature, frequency, and potential predictors of "major" toxic reactions. Thirty one methotrexate-treated patients (33%) and 11 patients (30%) receiving azathioprine experienced a major toxic reaction during the study period. With the case-control method, no predictors of major toxic reactions secondary to azathioprine therapy were found. Sex, drug dosage, response to prior slow-acting antirheumatic drug therapy, concurrent use of salicylates, and age did not predict major toxic reactions secondary to methotrexate treatment, but the methotrexate-treated patients who experienced a major toxic reaction had a significantly greater mean level of blood urea nitrogen at the time of their reaction compared with the control group. Life-table analysis suggested toxic reactions posed a greater risk of treatment termination in methotrexate-treated patients compared with the lack or loss of efficacy. This trend was not apparent in the azathioprine group. The majority of patients in each treatment group (79 for methotrexate and 29 for azathioprine) experienced one or more "minor" toxic reactions during the follow-up period. PMID- 2919942 TI - Endemic fluorosis with spinal cord compression. A case report and review. AB - We report a case of spinal cord compression in a Mexican immigrant due to vertebral osteosclerosis from chronic fluoride intoxication. Endemic fluorosis is acquired through drinking water. Groundwater sources with high fluoride content occur worldwide. The epidemiology, metabolism, and clinical features of fluorosis are reviewed. Greater physician awareness of this entity is important to identify correctly patients with this unusual and potentially devastating clinical disorder. PMID- 2919943 TI - Myocardial infarction: severe reversible ischemia and shock following excess thyroid administration in a man with normal coronary arteries. PMID- 2919944 TI - Salmonella arizona infections associated with ingestion of rattlesnake capsules. PMID- 2919945 TI - Pyomyositis in a patient with the acquired immunodeficiency syndrome. PMID- 2919946 TI - Antibiotic utilization. PMID- 2919947 TI - Catheter-related fungemia by Hansenula anomala. PMID- 2919948 TI - Desorption of aspirin from activated charcoal. PMID- 2919949 TI - Strongyloides. PMID- 2919950 TI - Serotonergic responsivity in male young adults with autistic disorder. Results of a pilot study. AB - Altered serotonergic function has been postulated to exist in autistic disorder. Central serotonergic responsivity was assessed with a neuroendocrine challenge test in seven male young adults with autistic disorder and in seven age- and gender-matched healthy controls. Binding indexes and physiologic responsivity of the platelet serotonin-2 (5-HT2) receptor complex were also measured, as was whole-blood serotonin content. Compared with controls, autistic subjects had substantially blunted prolactin release in response to a 60-mg oral dose of fenfluramine hydrochloride, an indirect serotonin agonist [corrected]. Furthermore, the magnitude of serotonin-amplified platelet aggregation, mediated by the platelet 5-HT2 receptor complex, was reduced in the autistic group, as was the mean number of platelet 5-HT2 receptor sites. Among autistic subjects, fenfluramine-induced prolactin release correlated positively with the serotonin amplified platelet aggregation response and negatively with whole-blood serotonin content. The results of the present study are compatible with the hypothesis that central serotonergic responsivity is decreased in male autistic young adults. Correlations between central and peripheral serotonergic measures in autistic subjects suggest that systemic alterations in serotonergic function may occur in autism. PMID- 2919951 TI - Age of alcoholism onset. I. Relationship to psychopathology. AB - Numerous attempts have been made to subdivide populations of alcoholics into homogeneous subgroups. Although no consensus has been reached about the characteristics of these subgroups, a number of classification schemes have identified a subgroup of patients with a high genetic loading for alcoholism, an early onset of alcoholism, a severe course, and coexisting psychiatric problems consisting of aggressive tendencies or criminality. In a recent typology proposed by Cloninger on the basis of adoption studies, this subgroup has been classified as type 2. Another group of patients who were found to differ in their mode of inheritance and clinical characteristics was classified as type 1. The identification of etiologically homogeneous subgroups is easier in studies of adoptees than in studies of individuals who were not adopted. In an attempt to divide alcoholics into two groups of individuals presenting type 1 and type 2 characteristics, we used as a criterion the age of alcoholism onset because type 2 alcoholics as well as their fathers had been found to abuse alcohol at a younger age than type 1 patients. Patients with an onset of alcoholism before their 20th birthday were found to have a significantly higher incidence of paternal alcoholism and were twice as likely to have been incarcerated for crimes involving physical violence. We also observed other features not previously described in this patient subgroup. Patients who started abusing alcohol in their teens were three times as likely to be depressed and four times as likely to have attempted suicide as patients with a later onset of alcohol abuse. PMID- 2919952 TI - Age of alcoholism onset. II. Relationship to susceptibility to serotonin precursor availability. AB - Alcoholics who start abusing alcohol early in life have been found to exhibit problems with mood and aggression control more frequently than patients with a later onset of alcoholism. Because alcohol preference and consumption, as well as mood and aggression regulation, are believed to be influenced by serotonin, relationships between tryptophan availability and mood and aggression regulation were explored in alcoholics. When studied in the entire population, the ratio of tryptophan over other amino acids competing for brain entry (which influences brain serotonin) was found to be lowest one day after cessation of drinking and to increase progressively over the following two to three weeks. When the population was divided into two groups of patients according to whether subjects started abusing alcohol before or after 20 years of age, associations between a low tryptophan ratio and depressive and aggressive tendencies were significant only in the subgroup of patients with an early onset of alcoholism. They were not significant in the rest of the population. Our data are compatible with the interpretation that patients with an early onset of alcoholism have a preexisting serotonin deficit that could manifest itself by an increased alcohol intake early in life and by an increased vulnerability to fluctuations in precursor availability. PMID- 2919953 TI - Biochemical classifications of diagnostic subgroups and D-type scores. PMID- 2919954 TI - Normal beard growth and testicular volume in depressed men. PMID- 2919955 TI - Buspirone reduces smoking. PMID- 2919956 TI - College of American Pathologists Conference XIV. Safety in transfusion practices revisited. August 17-19, 1988. Proceedings. PMID- 2919957 TI - Safety in transfusion practice. Is it safe to eliminate the major crossmatch for selected patients? AB - If a patient has no clinically significant unexpected antibodies, a major crossmatch is not required prior to blood transfusion so long as a test method that demonstrates ABO incompatibility is done. In this study, the safety of using a noncrossmatch method for detecting ABO incompatibility was compared with the use of an immediate spin crossmatch (ISCX). This noncrossmatch method consisted of the duplicate ABO testing of blood recipients, the repeated ABO testing of donor blood, and a clerical check to assure that only ABO matched or compatible blood was selected for transfusion. During the one-year study, 7124 patient samples were tested in duplicate for ABO, 26,942 U of red blood cells received from blood collection facilities were retested for ABO, and 23,962 U of blood selected for transfusion based on the noncrossmatch method were tested by an ISCX. ABO test results were concordant for 7115 of 7124 patient samples and discordant for nine. Seven of the nine discordant patient test results were resolved prior to transfusion, and two were inadvertently overlooked. ABO test results were concordant for 26,922 of 26,942 donor units and discordant for 20. Seventeen of the 20 discordant donor test results were resolved prior to transfusion and three were inadvertently overlooked. Two ABO incompatibilities were missed by the noncrossmatch method but were detected by the ISCX. Unless clerical errors can be totally eliminated, it may be safer to retain the ISCX. PMID- 2919958 TI - Transfusion practice in the private hospital. AB - Recognition that human immunodeficiency virus could be transmitted by blood transfusion has brought the practice of transfusion medicine into the public consciousness with great force. Patients are informed about the dangers of receiving a blood transfusion and are expressing their preferences about the source of the blood they may receive and the conditions under which they may receive it. Government, blood bank organizations, and physicians are responding to the public demand for a safe blood supply. As a result, profound changes are underway in hospital blood donor services, transfusion service inventory controls, and patient transfusion practices. A much more bureaucratic and complex system has emerged. Providing help to patients and physicians as they struggle to cope with the vicissitudes of this confusing new transfusion medicine is the role of the medical director of the hospital blood bank. PMID- 2919959 TI - The academic hospital blood bank director. All things to all people. AB - The in situ academic full-time hospital blood bank director is the best person to provide staff education, ensure optimal patient care, and encourage transfusion medicine research. The blood center medical director is too far away, and the part-time blood bank director is often too disinterested or overcommitted to other tasks to function on an equal level. By "being there," the academic blood bank director becomes the best role model for the young physician wishing for a career in transfusion medicine. PMID- 2919960 TI - The duty to warn about transfusion risks. AB - Blood banks and transfusion services should anticipate that patients contracting transfusion-transmitted diseases will claim that these facilities have a duty to warn or notify patients of potential transfusion risks. Although physicians treating patients must secure informed consent by describing significant risks and possible alternatives, precedent does not support extending informed consent requirements to the hospital or blood bank. Nonetheless, efforts to find new sources of compensation may cause judges to develop new theories of liability. Blood bank and transfusion service medical directors, therefore, are advised to provide clinicians with information regarding current or emerging transfusion risks and alternatives such as autologous transfusion, urging communication to patients when informed consent is obtained. PMID- 2919961 TI - The efficacy of oral antimicrobials in reducing aerobic and anaerobic colonic mucosal flora. AB - We investigated the impact of intestinal antisepsis on the colonic mucosa associated flora. Four groups of dogs were studied: group A received no bowel preparation, group B received a three-day clear-liquid diet, group C underwent mechanical cleansing of the bowel, and group D had mechanical cleansing followed by oral neomycin and erythromycin. Mucosal biopsy specimens were obtained for bacteriologic and scanning electron microscopic (SEM) studies. No significant difference in recovery of mucosal bacteria was observed between groups A and B. A significant decrease in recovery of aerobes was observed in group C, and a significant decrease in both aerobes and anaerobes was observed in group D compared with group A; Enterobacteriaceae and Bacteroides were either eliminated or greatly reduced. The SEM analysis of group D revealed a marked decrease in mucosa-associated microflora compared with groups B and C. Oral neomycin erythromycin produced a significant quantitative reduction in the colonic mucosa associated bacterial population, including the potentially pathogenic Escherichia coli and Bacteroides fragilis group isolates. These mucosa-associated bacteria are a likely source of contamination of the abdominal cavity and wound at the time of colon surgery. PMID- 2919962 TI - Emergency abdominal operations in the patient with acquired immunodeficiency syndrome. AB - We have reviewed the medical records of ten patients with acquired immunodeficiency syndrome who required emergency celiotomy in a three-year period. These operations are characterized by a high morbidity and mortality. Careful attention to the support of these immunosuppressed, malnourished patients if emergency operation is necessary may improve the poor results reported herein. PMID- 2919963 TI - Gallbladder response to enteral lipids in injured patients. AB - Severely injured patients are at risk for complications of gallbladder stasis in a spectrum from sludge formation and cystic duct occlusion by inspissation and, subsequently, acalculous cholecystitis. In a double-blind randomized trial, the effect of enteral lipids on the ability of the gallbladder to clear itself was tested. The gallbladder was assessed by ultrasonography for acute contractions, sludge and dilatation on days 1, 3, and 7 after injury. There were no significant differences between patients who received enteral lipids and controls. Both groups showed modest enlargement of the gallbladder and failure of contraction. In a population at risk for biliary stasis following severe trauma, standard enteral lipids did not elicit, acutely or chronically, an appropriate reflexive evacuation of the gallbladder. PMID- 2919964 TI - Is extensive lymphadenectomy necessary for surgical treatment of intramucosal carcinoma of the stomach? AB - This study was undertaken to elucidate those histological and gross features associated with gastric carcinoma that can be adequately treated by gastrectomy with less aggressive lymphadenectomy. The frequency of metastasis to the lymph nodes was analyzed in 514 cases of resected, solitary, gastric carcinomas. The frequency of metastasis to the lymph nodes increased in proportion to the increase in the extent of penetration by the cancer into the gastric wall. Lymph nodes were not involved in cases of intramucosal carcinoma of the intestinal type, by Lauren's histological classification. By contrast, metastasis to the lymph nodes was observed in cases of intramucosal carcinoma of the diffuse type, by Lauren's classification. We conclude that extensive lymphadenectomy is not mandatory for patients with intramucosal carcinoma of the stomach of the protruded type, since the lymph nodes do not become involved in this type of gastric carcinoma. PMID- 2919965 TI - DNA ploidy and tumor invasion in human gastric cancer. Histopathologic differentiation. AB - The relationship between DNA ploidy and tumor invasion in 254 patients with gastric carcinoma was studied, with particular emphasis on histopathologic features. In the differentiated type of adenocarcinoma, there were aneuploid lesions characterized by a relatively high incidence of lymph node metastasis and hematogenous recurrence, even when the invasion was limited to the submucosa. In the undifferentiated type, aneuploid lesions were rarely seen at the early stage, but the frequency remarkably increased with invasion into the deeper layers. Nodal involvement and disseminating metastasis were evident with serosal invasion. Analyzed by a multivariate Cox model, DNA ploidy significantly correlated with prognosis. Thus, DNA ploidy is a major determinant of survival, and the behavior of an aneuploid carcinoma is apparently controlled by individual histologic type. PMID- 2919966 TI - Guidelines for practical utilization of intraoperative frozen sections. AB - We reviewed 4057 intraoperative frozen sections from 1980 through 1984 to assess the accuracy, strengths, and weaknesses of this technique. Breast, lymph node, and skin comprised half of the sites evaluated. Frozen-section and final diagnoses agreed in 91.5% and disagreed in 6.8% of the cases; 1.7% of the cases were deferred. False-negative frozen-section diagnoses were due to pathologist sampling or judgment errors and surgeon sampling errors. There were eight (0.15%) false-positive diagnoses, none of which altered patient treatment. We recommend that lymph nodes for lymphoproliferative disorders and breast tissue for which a malignant diagnosis will not result in an immediate mastectomy not be submitted for frozen-section diagnosis. Appropriate studies of these tissues can be carried out without an intraoperative diagnosis; such a policy will increase the cost effectiveness of frozen sections without compromising patient care. PMID- 2919967 TI - Computed tomography and diagnostic peritoneal lavage in blunt abdominal trauma. Their combined role. AB - We reviewed medical records and films of all 196 trauma patients who underwent computed tomography (CT) between June 1982 and October 1986 to see whether CT achieved the level of accuracy attributed to it, whether diagnostic peritoneal lavage (DPL) performed in conjunction with CT was a useful diagnostic test for blunt abdominal trauma, and whether laparotomy was mandatory when pelvic fluid collections were seen by CT after blunt trauma. A total of 36 patients underwent DPL, 29 before and seven after CT. There were seven false-negative CTs that were clinically significant. Diagnostic peritoneal lavage was positive in three patients who had false-negative CTs. Although overall accuracy was excellent, CT was not reliable in detecting bowel injury. Diagnostic peritoneal lavage was helpful in detecting injuries missed by CT. Most stable patients with moderate or large intraperitoneal fluid collections on CT accompanying solid viscus injury were treated successfully without laparotomy. PMID- 2919968 TI - Physiologic effects of steep positioning in the surgical intensive care unit. AB - Ten hemodynamically stable patients requiring mechanical ventilation for radiographically symmetric acute lung disease were studied during steep lateral positioning and continuous rotation in a Roto Rest kinetic treatment bed. There were no significant hemodynamic or ventilatory differences among the four positions (supine, right side down, left side down, and rotating). In four patients, arterial oxygen pressure (PaO2) decreased 16% to 49% in the lateral position when compared with the supine position. Continuous rotation restored the PaO2 toward the supine value in each patient. In six patients, PaO2 increased 11% to 35% during lateral positioning. In five of the six patients, the increase in PaO2 differed between sides, suggesting asymmetric lung disease. Continuous rotation did not significantly alter the PaO2 from the supine values in these patients. Adverse effects on oxygenation caused by positional changes may be reversed by continuous rotation using the Roto Rest kinetic bed. PMID- 2919969 TI - Nosocomial abscess. Results of an eight-year prospective study of 32,284 operations. AB - This article details the results of 114 abscesses found after 32,284 operations during a 30-day prospective infection surveillance. Abscesses occurred more often after gastric/esophageal (3.6%), colonic/appendiceal (2.8%), and pancreatic/biliary (1.5%) operations. Abscesses were intra-abdominal (58%), pelvic/perineal (31%), and retroperitoneal (3%). The most common pathogens were Escherichia coli, enterococci, and Bacteroides organisms. Abscess symptoms appeared 10 +/- 6 days (mean +/- SEM) after surgery and were drained 8 +/- 8 days after onset of symptoms. Hospital stay from onset of symptoms to discharge was four times greater than that for wound infection. Twenty-seven patients (28%) died. Mortality was increased in patients older than 50 years and in those with renal failure or multiple abscesses. Nosocomial abscesses had a greater morbidity than would infection. Excessive expense and high mortality warrant infection surveillance for both wound infection and ongoing nosocomial abscesses. PMID- 2919970 TI - Influence of estrogen receptors on survival and recurrence in patients with breast cancer without lymph node metastases. AB - A retrospective chart review was conducted to determine the prognostic effect of estrogen receptor (ER) protein in patients with node-negative operable breast cancer. One hundred nine patients with breast cancer whose tumors underwent ER analysis and whose lymph node negativity was established histologically were studied. Based on life-table analysis, the overall survival at six years was 92.7% for ER-positive patients, 95.3% for ER-negative patients, and 94.4% for ER borderline patients. The disease-free survival was 83.3%, 92.8%, and 71.4%, respectively. Survival and disease-free survival were also correlated to menopausal status. The difference in survival was not statistically significant at six years. We conclude that in node-negative primary operable breast cancer, ER status should not be used as a discriminant for adjuvant treatment. PMID- 2919971 TI - A foregut carcinoid tumor causing Zollinger-Ellison syndrome. AB - A patient had severe peptic ulcer disease complicated by gastric outlet obstruction and choledochoduodenal fistula. Serum gastrin levels were elevated preoperatively to 340 ng/L. A 1.5-cm histologically benign carcinoid tumor of the antrum of the stomach was found at surgery, and surgical resection of the tumor resulted in normalization of serum gastrin levels and amelioration of the peptic acid diathesis. The patient remains asymptomatic at one year. Immunohistochemical staining demonstrated that the carcinoid indeed contained gastrin along with chromogranin, cholecystokinin, and neuron-specific enolase. This is a case of Zollinger-Ellison syndrome caused by a benign foregut carcinoid (gastric carcinoid-gastrinoma). PMID- 2919972 TI - Cefotetan-associated coagulopathies. PMID- 2919973 TI - Spontaneous renal rupture in pregnancy. PMID- 2919974 TI - Aphasia therapy: more than just hand-holding. PMID- 2919976 TI - Systemic interferon alfa in multiple sclerosis. PMID- 2919975 TI - Listeria brain abscess in the acquired immunodeficiency syndrome. PMID- 2919977 TI - Chronic myelopathies associated with human T-lymphotropic virus type I. A clinical, serologic, and immunovirologic study of ten patients in France. AB - Chronic myelopathy associated with human T-lymphotropic virus type I (HTLV-I) has been described in HTLV-I endemic areas. In Paris, 167 neurologic patients were screened for HTLV-I by enzyme-linked immunosorbent, indirect immunofluorescent, and Western blot assays. Ten of the 11 patients with positive results had a chronic spastic paraparesis with IgG oligoclonal bands and elevated HTLV-I antibody index. Two of them had been born and were living in France, without HTLV I risk factors. Evoked potentials were abnormal in the nine tested patients and brain magnetic resonance images in three of seven patients. No improvement was observed with steroid treatment. A retrovirus similar to HTLV-I was isolated in five cases at different periods of the disease. Hypotheses of limited endemic areas in western countries are discussed. Early presence and persistence of HTLV I suggest that it is the etiologic agent. PMID- 2919978 TI - Human immunodeficiency virus type 1 antigen in cerebrospinal fluid. Correlation with clinical neurologic status. AB - Human immunodeficiency virus type-1 (HIV-1) antigen was assayed in paired serum/cerebrospinal fluid (CSF) specimen from 85 adults and 58 children with acquired immunodeficiency syndrome and was compared with clinical neurological status. A quantitative comparison of HIV-1 antigen levels in matched serum and CSF specimens indicated that HIV-1 antigen expression in these compartments is independent and is correlated with acquired immunodeficiency syndrome dementia complex in adults and progressive encephalopathy in children. In a longitudinal study (n = 47), 16 patients tested positive for HIV-1 antigen in the CSF before (n = 2) or coincident (n = 14) with neurological deterioration. Six patients who tested positive for HIV-1 antigen in the CSF remained neurologically normal for a median duration of follow-up of 11 months. Six of 25 patients who tested negative for HIV-1 antigen in the CSF, subsequently showed neurological deterioration. These data indicate that HIV-1 antigen expression in the CSF is not useful in predicting neurological deterioration. PMID- 2919979 TI - Neurologic involvement in Behcet's syndrome. A prospective study. AB - We investigated the prevalence and type of neurologic involvement in Behcet's syndrome in a prospective protocol. Of 323 consecutive patients with Behcet's syndrome seen during a 12-month period, 46 underwent neurologic evaluation because of headaches and/or neurologic symptoms and signs. Only 17 (5.3%) were found to have involvement of the nervous system. Hemispheric lesions were as common as brain-stem involvement. Headaches were of no clinical importance unless accompanied by other neurologic findings. Computed tomographic scans were of little diagnostic help. After 12 +/- 4 (SD) months of follow-up, only three patients showed worsening of their neurologic findings. PMID- 2919980 TI - Cerebrospinal fluid immunoglobulin abnormalities in neurosarcoidosis. AB - A retrospective chart review of neurosarcoidosis at the University of Texas Medical Branch (Galveston) between 1982 and 1987 revealed 99 patients with sarcoidosis. Six patients were diagnosed with neurosarcoidosis and had electrophoresis of serum and cerebrospinal fluid performed (one patient with a ventriculoperitoneal shunt was later excluded). Cerebrospinal fluid immunoglobulins and albumin levels were determined followed by calculation of an IgG index and synthesis rate for each patient. Four (80%) of five patients had elevated IgG indexes and synthesis rates indicative of intrathecal immunoglobulin production. No patient had immunoglobulin oligoclonal bands detected. To date, results of electrophoresis of cerebrospinal fluid in neurosarcoidosis have been reported in 37 patients among four series. Of these, only nine patients (24%) have had either an elevated IgG index or synthesis rate. Our series suggests that intrathecal immunoglobulin production in neurosarcoidosis occurs more frequently than previously described. Furthermore, the elevated indexes and synthesis rates without associated oligoclonal bands suggests a polyclonal immunoglobulin response. PMID- 2919981 TI - Relation of personality and attentional factors to cognitive deficits in human immunodeficiency virus-infected subjects. AB - In view of the evidence that patients with human immunodeficiency virus infection experience reactive depression and anxiety, it is important to determine whether these factors might account for some of the cognitive deficiencies observed in this group, as is often the case in psychiatric populations. An extensive battery of cognitive, personality, and attention tests was administered to 26 patients who tested positive for the human immunodeficiency virus. In this group were patients who demonstrated no symptoms, patients who had acquired immunodeficiency syndrome-related complex, and patients who had acquired immunodeficiency syndrome. Pearson Product Moment correlations were computed between scores on the three types of measures. The results of this correlational study suggest that cognitive decline in patients infected with human immunodeficiency virus is independent of mood and attentional changes. PMID- 2919982 TI - Vertigo of vascular origin. Clinical and electronystagmographic features in 84 cases. AB - We reviewed the clinical and electronystagmographic findings of 84 patients who presented to our neuro-otology clinic with vertigo of presumed cerebrovascular origin. There was a surprisingly high incidence of isolated episodes of vertigo (abrupt in onset, lasting minutes). In some patients these episodes preceded other symptoms of vertebrobasilar insufficiency or infarction by months. Peripheral vestibular abnormalities were common on electronystagmographic testing; 42% had unilateral hypoexcitability to caloric stimulation. We conclude that the vestibular labyrinth is selectively vulnerable to ischemia within the vertebrobasilar system. PMID- 2919983 TI - The intracarotid amobarbital sodium procedure. False-positive errors during recognition memory assessment. AB - Memory performance during the intracarotid amobarbital sodium (Amytal sodium) procedure was examined in 40 patients as part of their diagnostic work-up as candidates for epilepsy surgery. Free recall was significantly better following right hemisphere injection although no left/right difference was present during recognition assessment. However, the occurrence of false-positive (FP) recognition errors was significantly more frequent following left hemisphere injection. In all conditions, no relationship to seizure focus was observed. Patients with FP errors displayed poorer delayed verbal memory during baseline neuropsychological assessment compared with patients without FP errors. Data indicate an inverse relationship between FP errors and recent verbal memory function, and they suggest that impaired memory rather than failure to suppress incorrect responses secondary to poor self-monitoring capacity is responsible for the generation of FP and intrusion errors. PMID- 2919984 TI - Interobserver agreement in the diagnosis of multiple sclerosis. AB - Interobserver agreement in the clinical diagnosis of multiple sclerosis (MS) among six neurologists was evaluated. Three of them participated in a study of the clinical diagnosis of MS, the Italian Multicenter Study (IMS). The raters examined the clinical forms of MS of 50 patients randomly selected from among 430 patients recruited from the IMS. For each patient, neurologists were asked to make a diagnosis according to the McDonald-Halliday classification system of MS. The overall agreement on the diagnosis (MS present or absent) was fair, with no difference noted between the two groups of raters. Considering the six diagnostic levels instead, the reliability was higher for the neurologists participating in the IMS program. These neurologists agreed particularly on the Clinically Definite and Progressive Possible classifications. Complete disagreement was observed for the Early Probable or Latent and Progressive Probable classifications. Because of the different level of agreement on diagnosis, we suggest separate consideration of Clinically Definite and Progressive Probable MS cases in clinical trials and epidemiologic studies of this disease. PMID- 2919985 TI - Brain-stem auditory evoked potential abnormalities with unilateral brain-stem lesions demonstrated by magnetic resonance imaging. AB - We correlated the brain-stem auditory evoked potential (BAEP) abnormalities in 24 patients with discrete unilateral brain-stem lesions demonstrated by magnetic resonance imaging. In 18 patients who had BAEP abnormalities either confined to or more severe on stimulation of one ear, the lesion on magnetic resonance imaging was in the brain stem ipsilateral to the corresponding ear. Mesencephalic lesions produced amplitude abnormalities of the IV/V complex while pontine lesions resulted in abnormalities of earlier components (wave II and/or III). Prolongation of the I-III interpeak latency tended to occur with pontine lesions and of the III-V interpeak latency with mesencephalic lesions. Unilateral brain stem lesions, particularly at the mesencephalic level, often produced BAEP abnormalities on both ipsilateral and contralateral monaural stimulation. PMID- 2919986 TI - Post-traumatic anosmia. Ultrastructural correlates. AB - Five patients suffering post-traumatic anosmia were studied at the University of Colorado Health Sciences Center, Denver. Each patient underwent psychophysical testing, clinical evaluation, and olfactory biopsy. The biopsy specimens were examined ultrastructurally and were found to vary from normal tissues. The overall appearance of the olfactory epithelium in the post-traumatic patient is disrupted and the receptor cells are distorted. Large numbers of axons are located near the basement membrane and can often be found in bundles throughout the epithelium, extending even to the mucosal surface. Olfactory cilia are rarely seen in epithelia obtained from post-traumatic patients. Bald olfactory vesicles, often containing basal bodies, are frequently observed. We postulate that in these cases, the olfactory epithelium regenerates following head trauma and the receptor cells attempt to send axons centrally. However, the cribriform plate has undergone fibrotic healing and the axons are unable to penetrate it and make contact with olfactory bulb neurons. PMID- 2919987 TI - Anterior speech region. Asymmetry and weight-surface correlation. AB - Results of this work show, in the inferior frontal gyrus and in the different portions into which it was divided, asymmetry of weight and cortical surface and left predominance in the posterior portion, which is concerned with language. In spite of the difference among the absolute individual values, the correlation between weight and surface values is excellent in all cases, and the weight and surface ratio is the same for the portions related to language and different for the remainder of the inferior frontal gyrus. PMID- 2919988 TI - Divided attention, as measured by dichotic speech performance, in dementia of the Alzheimer type. AB - To determine if impaired dichotic performance in patients with dementia of the Alzheimer type is due to the inability to divide attention or the inability to perceive degraded auditory stimuli, we measured performance on tasks of both dichotic and degraded monotic speech materials. We also examined whether perception of degraded speech stimuli presented monaurally is related to abnormalities of temporal lobe anatomy and physiology, as we have shown for dichotic performance. Although the patients were impaired on both dichotic and monotic tests, significantly greater impairment was seen on the dichotic test. Our earlier finding of a significant relation between dichotic performance and measures of anterior temporal lobe atrophy and reduced glucose metabolism was replicated, but no significant relation was found between monotic tests and measures to temporal lobe integrity. We conclude that the inability to divide attention, rather than abnormal processing of degraded stimuli per se, is reflected in poor dichotic performance in patients with dementia of the Alzheimer type, and that dichotic performance, unlike degraded monotic perception, depends directly on the integrity of temporal cortex in these patients. PMID- 2919989 TI - Consensus and controversy in neurologic practice. The case of steroid treatment in multiple sclerosis. PMID- 2919990 TI - Deep cerebral venous thrombosis. Clinical, neuroradiological, and neuropsychological correlates. AB - Thrombosis of the deep cerebral venous system is usually fatal, and patients are frequently stuporous or comatose at presentation. This report describes serial radiological and neuropsychological observations in an 18-year-old woman who remained alert and survived this disorder. In association with diencephalic edema seen on computed tomographic scan, she demonstrated disorientation, abulia, attentional deficits, memory loss, and dyscalculia and had impaired IQ scores: the performance scores were worse than the verbal scores. Significant aphasia or sensory loss was absent. She recovered full intellectual capacity in the course of follow-up examinations, and the diencephalic edema seen on the computed tomographic scan resolved despite persistent thrombosis of the straight sinus demonstrable on follow-up digital angiography. PMID- 2919991 TI - Persistent high-altitude headache and aguesia without anosmia. AB - High-altitude headache and taste dysfunction are usually cured within a few months by descent to sea level. We studied a patient who had persistent bitemporal throbbing headache with the associated findings of high-altitude headache syndrome 15 years after a compression chamber accident. He also had loss of taste without loss of smell since the incident. PMID- 2919992 TI - Osmotic demyelination syndrome. Lack of pathologic and radiologic imaging correlation. AB - An otherwise healthy diabetic woman developed severe hyponatremia, her serum sodium ion levels were rapidly corrected to normal, and she had a course of improvement then neurologic deterioration, with seizures and coma developing in the subsequent two days. Imaging studies, including computed tomography and magnetic resonance images of the brain as late as 19 days after the osmotic insult, failed to show pathologically demonstrated demyelinating lesions. Osmotic brain injury induces demyelination in areas of gray-white apposition and, clinically, results in a delayed neurologic deterioration one to three days following the osmotic challenge. Even with magnetic resonance imaging, review of the literature and this experience suggest that osmotic demyelination cannot reliably be imaged during the first month after the insult. PMID- 2919993 TI - Breast cancer: role of postoperative radiotherapy. PMID- 2919994 TI - Non-seminomatous testicular cancer, 1989: primum non nocere. PMID- 2919995 TI - Do big breasts disadvantage women with breast cancer? AB - The present study was undertaken in order to discover whether patients with breast cancer in large breasts experienced a delay in the detection of their cancer due to the bulk of the breast and consequently presented with more advanced tumours compared with women with small breasts. Mastectomy specimens were weighed and their dimensions measured, in particular recording breast mass and breast thickness (anterior-posterior depth). Tumour diameter, the number of involved lymph nodes and the oestrogen and progesterone receptor levels were measured as prognostic indices. Although there was no difference in receptor status of tumours from large and small breasts, on presentation, patients with big breasts had larger tumours and more involved lymph nodes than women with small breasts, whether breast size was assessed by weight or thickness. Women with large breasts may therefore be expected to fare worse than those with small breasts. PMID- 2919996 TI - Splenectomy for immune thrombocytopenic purpura: Auckland experience 1979-87. AB - Of 148 elective splenectomies performed in Auckland during 1979-87, 48 were performed as therapy for immune thrombocytopenic purpura (ITP). In all cases medical therapy had either failed to maintain their platelet count (36 patients), or side-effects of medical treatment had made continuation unacceptable (12 patients). The mean age of the group was 31 years and there were 15 males and 33 females. Thirty-four of 48 patients (71%) had a favourable response to splenectomy: platelet count was maintained above 150 x 10(9)/l and medical therapy was no longer required. There was no operative or inhospital mortality. Seven patients experienced postoperative complications (mainly infections) of which none were life-threatening. There was no difference in response between males and females (67% and 73% response rate, respectively), and the response rates of Europeans and non-Europeans were similar (71% and 69%, respectively). By contrast, the average age of the responders [29 years) was almost 10 years younger than the non-responders (38 years). It is concluded that the use of splenectomy as therapy for patients with ITP, who have either failed to respond to medical management or for various reasons cannot tolerate the complications associated with steroid therapy, is a safe procedure which in the present series was associated with no operative mortality and an acceptably low rate of morbidity. Younger ITP patients (less than 30 years) have a better chance of responding favourably to splenectomy than do older patients (greater than 40 years). PMID- 2919997 TI - Management of the traumatized liver: an appraisal of 63 cases. AB - A review of all patients with liver trauma admitted to the Royal Adelaide Hospital during the period 1983-86 was undertaken. Twelve of the 63 patients died. Liver trauma was responsible in eight (giving a mortality rate of 12.7%). The overall mortality rate was 19.0%. Most of the liver injuries (83%) were due to blunt trauma. All the deaths occurred in this group and were related directly or indirectly to blood loss. A high mortality (83%) was associated with hepatic vein injury. Right hepatectomy was unsuccessful in preventing death in any of these patients. The management of major venous injuries is discussed. A significant number of the liver injuries was minor. Analysis of these suggests that a more conservative approach to the management of haemodynamically stable patients might be appropriate. PMID- 2919998 TI - Revision total hip arthroplasty using uncemented components: preliminary report. AB - Revision of failed cemented total hip arthroplasties represents a major technical challenge to orthopaedic surgeons. One of the problems encountered is loss of femoral bone stock, making restoration of prosthetic stability difficult. Revision with uncemented components may allow healing of bone defects. PMID- 2919999 TI - Huckstep nail arthrodesis of the knee: a salvage for infected total knee replacement. AB - Seventeen patients had Huckstep Nail arthrodeses of the knee as a salvage for infected total knee replacements. All patients were followed prospectively for an average of 22.6 months. All patients were satisfied with their results. There was one broken nail secondary to non-union, and three other patients with non-unions (two of whom were asymptomatic). It is believed that this is a reliable method of treatment in selected patients. It has a number of advantages over other techniques. In addition, a two-staged operative method with a number of technical improvements is outlined. PMID- 2920000 TI - Intestinal atresia: factors affecting survival. AB - Eighty-four patients with congenital jejuno-ileal or colonic atresia treated at this hospital during the years 1961-86 were studied. There were 42 cases of jejunal atresia, seven cases of jejuno-ileal atresia, 33 cases of ileal atresia and two cases of colonic atresia. Multiple atresias occurred in 19 patients. During the first 15 years of the study the mortality rate was 56%. In the last 10 years it was 22%. Multivariate linear modelling techniques were used to determine the factors associated with a fatal outcome. In order of magnitude associations were found between death and year of treatment (P less than 0.01), the type of anastomosis performed to correct the atresis (P less than 0.05), the presence of other congenital abnormalities (P less than 0.01) and presence of a malrotation (P less than 0.02). The anastomoses associated with the highest mortality were those with a stoma. The mean length of bowel resected proximal to the anastomosis was 15 cm and the mean length resected distally 5 cm. Eleven patients had 60 cm or less of small bowel remaining after surgery and only three of these survived. The highest mortality rate can be expected in patients with other congenital abnormalities and those with a malrotation. A primary anastomosis without a stoma is recommended. PMID- 2920001 TI - Simplified hepatectomy: the tourniquet method. AB - A method to control bleeding from the transected liver parenchyma during hepatectomy is described. The merits of this tourniquet method are its simplicity and versatility. It is inexpensive, can be applied rapidly and performed readily. Hepatic transection, particularly in a cirrhotic liver, can be effected with a substantial reduction in blood loss. PMID- 2920002 TI - Transcutaneous oxygen potentials in venous disease. AB - Abnormal levels of transcutaneous tissue oxygen tension (TcPO2) have been reported in venous disease but the most appropriate application of the technique to the study of venous disease is not clear. Patients with mild (superficial varicosities) and severe venous disease (ulcers and/or skin changes) and normal controls were studied. Four variables derived by measurement of TcPO2 were used for comparison between groups. The peak postischaemic response was reduced markedly in patients with severe venous disease and may be the most appropriate way of applying TcPO2 measurements to investigation of venous disease. The findings support the theory that a diffusion block to oxygen exists in severe venous disease. PMID- 2920003 TI - Secretion of antidiuretic hormone in neurosurgical patients: appropriate or inappropriate? AB - In neurosurgical patients with hyponatraemia (plasma sodium less than 130 mmol/l) and natriuresis, increased antidiuretic hormone (ADH) secretion may be appropriate rather than inappropriate. Ten such patients were studied prospectively to assess circulating ADH concentration and body fluid volumes. Compared with a control group, the mean plasma ADH level was significantly elevated (0.9 pmol/l (s.e.m. = 0.2) versus 0.2 pmol/l (s.e.m. = 0.1], the total body water was normal (101% (s.e.m. = 3) versus 100% (s.e.m. = 6], while the blood volume was significantly reduced (89% (s.e.m. = 3) versus 104% (s.e.m. = 5]. The elevated ADH level was therefore appropriate to a reduced blood volume. This suggests that, in neurosurgical patients with hyponatraemia, fluid restriction could be dangerous. Serial observations in this small group of patients showed that salt replacement and normal fluid intake resulted in a fall in the elevated ADH levels. PMID- 2920004 TI - Replantation of an excised segment of radial forearm tissue. AB - A report on a case of successful replantation of an excised segment of forearm tissue is presented. An 18 year old man was admitted to hospital with a completely excised segment of the radial side of his forearm and wrist as a result of a circular saw injury. The best reconstructive option was replantation of the excised radial forearm tissue thus providing both soft tissue cover and bony stabilization. PMID- 2920005 TI - A computer model for unconscious spread of anxiety-linked inhibition in cognitive networks. AB - Unconscious inhibitory processes, triggered by a potential anxiety reaction, are reviewed in the context of an emerging rapprochement between psychodynamic and cognitive approaches in experimental psychology. Conditions underlying spread of inhibitory action to other cognitive networks are first explored in three tachistoscopic experiments utilizing words posthypnotically tied to a potential anxiety, pleasure, or neutral reaction. Response times of subjects, instructed to ignore those words while naming pictures or solving anagrams as quickly as possible, reveal a highly differentiated pattern of circumstances governing likelihood of inhibitory spread from anxiety-linked words to target stimuli. Next a computer model is constructed to simulate cognitive processes from onset of display to eventual response, and the model is then tested for its fit to the empirical data. Finally, an illustrative study shows that a subset of computer generated predictions for spread of inhibitory action is verifiable experimentally. PMID- 2920006 TI - Correlation of neuropathy target esterase activity with specific tritiated di isopropyl phosphorofluoridate-labelled proteins. AB - Neuropathy target esterase (NTE) is a membrane-bound carboxylesterase activity that has been proposed as the target site for initiation of organophosphate induced delayed neuropathy. This activity is identified by its resistance to treatment with Paraoxon and sensitivity to co-incubation with Paraoxon and Mipafox. Sucrose-density-gradient centrifugation of membrane-associated proteins isolated from chick-embryo brains identified three proteins, Mr 161,000, 116,500 and 103,000, that were labelled with [3H]di-isopropyl phosphorofluoridate in an NTE-like manner and that co-migrated with NTE. The 161,000-Mr and 116,500-Mr proteins were identified in both adult and embryo brain. One or both of these proteins may therefore contribute to the activity defined as NTE. In addition, a 61,000-Mr protein was identified that does not comigrate with NTE, but that was labelled with [3H]di-isopropyl phosphorofluoridate in a Paraoxon-resistant and Mipafox-sensitive manner. The effect of Mipafox on labelling, however, was reversibly blocked by co-incubation with Paraoxon. This protein, therefore, is not NTE, but has the necessary inhibitor-sensitivity to be the target site for organophosphate-induced delayed neuropathy. PMID- 2920007 TI - Unfractionated heparin inhibits thrombin-catalysed amplification reactions of coagulation more efficiently than those catalysed by factor Xa. AB - We have proposed previously that the steps in coagulation most sensitive to inhibition by heparin are the thrombin-dependent amplification reactions, and that prothrombinase is formed in heparinized plasma only after Factor Xa activates Factor VIII and Factor V. These propositions were based on the demonstration that both heparin and Phe-Pro-Arg-CH2Cl completely inhibited 125I prothrombin activation for up to 60 s when contact-activated plasma (CAP) was replenished with Ca2+. Furthermore, the addition of thrombin to CAP before heparin or Phe-Pro-Arg-CH2Cl completely reversed their inhibitory effects. Additional support for the above hypotheses is provided in this study by demonstrating that, when the activity of thrombin is suppressed by heparin (indirectly) or by Phe-Pro-Arg-CH2Cl (directly), exogenous Factor Xa reverses the ability of these two agents to inhibit prothrombin activation. Prothrombin activation was initiated by adding Factor Xa (1 nM) or thrombin (1 or 10 nM) simultaneously with CaCl2 to CAP. In the absence of heparin or Phe-Pro-Arg-CH2Cl, prothrombin activation was seen 15 s later in either case. Heparin failed to delay, and Phe-Pro-Arg-CH2Cl delayed for 15 s, prothrombin activation in CAP supplemented with Factor Xa. In contrast, heparin and Phe-Pro-Arg-CH2Cl completely inhibited prothrombin activation for at least 45 s in CAP supplemented with 1 nM-thrombin. Heparin failed to delay prothrombin activation in CAP supplemented with 10 nM-thrombin, whereas Phe-Pro-Arg-CH2Cl completely inhibited prothrombin activation in this plasma for 45 s. These results suggest that in CAP: (1) Factor Xa can effectively activate Factor VIII and Factor V when the proteolytic activity of thrombin is suppressed; (2) heparin-antithrombin III is less able to inhibit Factor Xa than thrombin; (3) suppression of the thrombin dependent amplification reactions is the primary anticoagulant effect of heparin. PMID- 2920009 TI - Structural similarity of chymopapain forms as indicated by circular dichroism. AB - Four chymopapain forms were isolated by high-resolution liquid chromatography on a cation-exchange column. The three major forms possess nearly identical secondary and tertiary structures, as judged from their c.d. spectra; these components showed similar proteolytic activity and Mr values close to that of papain. The fourth isolated component seems to be a mixture of modified proteins. PMID- 2920008 TI - Biochemical localization of the transformation-sensitive 52 kDa (p52) protein to the substratum contact regions of cultured rat fibroblasts. Butyrate induction, characterization, and quantification of p52 in v-ras transformed cells. AB - A 52 kDa protein (p52) was identified, using differential extraction and electrophoretic criteria, as a major extracellular and substrate-associated component of normal rat kidney (NRK) fibroblasts. Cells transformed with Kirsten murine sarcoma virus (KNRK cells) did not express p52 constitutively, but were inducible for both p52 production and its substrate association during culture in sodium butyrate (NaB)-supplemented growth medium. Comparative analysis of the relative molecular mass, subcellular distribution, and isoelectric complexity (five variants ranging in pI from 5.4 to 6.2) of the 52 kDa species constitutively and inducibly expressed by NRK and KNRK/NaB cells respectively, indicated that they were, indeed, the same protein. p52 selectively localized to cellular fractions enriched in substrate focal contact sites and associated ventral undersurface components. NaB induction of p52 in KNRK cells occurred before cell spreading; other polar compounds, such as dimethyl sulphoxide, which did not induce KNRK cell spreading, similarly failed to elicit p52 production. p52 accumulated more rapidly in (and was quickly released from) the focal-contact enriched protein fraction of NRK cells compared with its time course of appearance in the medium. These data collectively suggest that p52 is one of a relatively small number of proteins the synthesis of which is either involved in determination of cell shape or regulated as a consequence of cell-shape changes. PMID- 2920010 TI - Transient-time analysis of substrate-channelling in interacting enzyme systems. AB - The kinetics of dynamically interacting enzyme systems is examined, in the light of increasing evidence attesting to the widespread occurrence of this mode of organization in vivo. The transient time, a key phenomenological parameter for the coupled reaction, is expressed as a function of the lifetime of the intermediate substrate. The relationships between the transient time and the pseudo-first-order rate constants for the coupled reaction by the complexed and uncomplexed enzyme species are indicative of the mechanism of intermediate transfer ('channelling'). In a dynamically interacting enzyme system these kinetic parameters are composite functions of those for the processes catalysed by the complex and by the separated enzymes. The mathematical paradigm can be extended to a linear sequence of N coupled reactions catalysed by dynamically (pair-wise) interacting enzymes. PMID- 2920011 TI - Effect of heparin on the glia-derived-nexin-thrombin interaction. AB - In order to determine the specificity of the interaction between thrombin and glia-derived nexin (GdN), the inactivation of proteolytically modified human thrombin species by GdN has been studied. The second-order rate constants for the inactivation of alpha-, beta T-, gamma T- and epsilon-thrombin by GdN were 1.41, 0.63, 0.33 and 1.91 microM-1.s-1 respectively. The kinetic properties of gdN were also investigated in the presence of different types of heparin, fractionated according to antithrombin III-binding affinity. Association rate constants of both gdN and antithrombin III with alpha-thrombin were obtained using unfractionated, low- and high-affinity heparin types. The different heparin types gave optimal rates of inhibition at similar heparin concentrations for both inhibitors. At optimal heparin concentrations, the rate of inactivation of alpha thrombin by GdN was 0.5-1.2 nM-1.s-1, which suggests that, under these conditions, the interaction is diffusion-controlled. PMID- 2920012 TI - Glutathione transferases in rat hepatoma cells. Effects of ascites cells on the isoenzyme pattern in liver and induction of glutathione transferases in the tumour cells. AB - Rat hepatoma cells grown intraperitoneally as an ascites tumour were analysed with respect to their contents of cytosolic glutathione transferases. In contrast with normal liver tissue, the hepatoma cells were dominated by the class Pi glutathione transferase 7-7. All the major hepatic enzyme forms were down regulated to almost undetectable concentrations. Livers of rats bearing ascites hepatoma cells expressed low, but significant, amounts of protein which, by electrophoretic and immunochemical properties, appeared identical with transferase 7-7. This enzyme is not detectable in normal hepatocytes. Treatment of rats with trans-stilbene oxide induced the expression of transferase 7-7 in the livers of normal rats as well as in hepatoma-cell-bearing animals. In addition, a 2-fold induction of transferase 7-7 was measured in the hepatoma ascites cells. No significant elevation of any other enzyme forms in the hepatoma cells was noted. PMID- 2920013 TI - Physiological significance of the marked increased branching of the glycans of human serotransferrin during pregnancy. AB - Human serotransferrin (Tf) presents a microheterogeneity based on the existence of biantennary and triantennary glycans of the N-acetyl-lactosaminic type. By affinity chromatography on a concanavalin A-Sepharose column in well-defined conditions, human serotransferrin isolated from healthy donors was resolved into three carbohydrate molecular variants: Tf-I (less than 1%), Tf-II (17 +/- 2%) and Tf-III (82 +/- 3%) containing two triantennary glycans, one triantennary and one biantennary glycans and two biantennary glycans respectively. In addition, two 'isomers' of the triantennary glycans containing the third antenna beta-1,4 linked to the alpha-1,3-mannose residue or beta-1,6-linked to the alpha-1,6 mannose residue were characterized by methylation analysis in the ratio 1:1 in both Tf-I and Tf-II variants. On concanavalin A crossed immuno-affinity electrophoresis, the patterns exhibited by each of the three purified variants or by a mixture of these variants were compared with the patterns given by transferrin present in sera from nonpregnant and pregnant women. The results suggest that the relative proportions of transferrin carbohydrate variants was unchanged when the concentration of transferrin was increased in serum from normal donors, whereas in the serum of pregnant women, especially in the last 3 months of pregnancy, when the serum concentration of transferrin reached 4.5-5 g/l, the relative proportions of the carbohydrate variants Tf-I and Tf-II increased from 1 to 6 +/- 1% and from 17 +/- 2 to 26 +/- 3% respectively while that of Tf-III decreased from 82 +/- 3 to 67 +/- 3%. The binding of the three transferrin carbohydrate variants to the receptor of the syncytiotrophoblast plasma membranes was determined by using Scatchard-plot analysis. The number of binding sites remained constant with an increase in the number of triantennary glycans whereas a decrease up to 6-fold in the affinity constant was observed. Detection of the transferrin-receptor complex by immunoblotting in the presence of non-dissociating detergents revealed the existence of only one type of receptor or of a receptor possessing similar properties involved in the binding of each of the three serotransferrin carbohydrate variants. PMID- 2920014 TI - Uptake of retinyl ester in HL-60 cells via the low-density-lipoprotein-receptor pathway. AB - Newly absorbed retinol is transported in association with chylomicrons and their remnants. In addition, after intake of high doses of retinol, significant amounts are also found in low-density lipoprotein (LDL). As both chylomicron remnants and LDL may be taken up by cells via the LDL receptor, and retinoids inhibit proliferation of some leukaemic cells, we have studied the uptake of retinol in leukaemic cells via the LDL-receptor pathway. HL-60 cells contain saturable binding sites for LDL. The binding of LDL to its receptor has a dissociation constant of about 3.2 x 10(-9) M, and the number of receptors per cell was calculated to be about 2700. Uptake of 125I-LDL by HL-60 cells was increased 2 fold by preincubating the cells with mevinolin. The presence of specific receptors for LDL on HL-60 cells was further confirmed by the finding that exogenous LDL cholesterol was able to up-regulate the ACAT (acyl-CoA: cholesterol acyltransferase) activity of HL-60 cells. We then tested the uptake of retinyl ester in leukaemic cells via the LDL-receptor pathway. HL-60 cells were incubated with LDL or chylomicron remnants labelled with [3H]retinyl palmitate. Uptake of retinyl ester associated with both LDL and chylomicron remnants was observed. Furthermore, the presence of excess LDL decreased the uptake by 75-100%, supporting the hypothesis that the uptake of retinyl ester occurred via the LDL receptor in HL-60 cells. PMID- 2920015 TI - Altered enzyme activities and citrulline synthesis in liver mitochondria from ornithine carbamoyltransferase-deficient sparse-furash mice. AB - Male mice carrying the spfash mutation have 5-10% of the normal activity of ornithine carbamoyltransferase, yet are only slightly hyperammonaemic and develop quite well. A study of liver mitochondria from normal and spfash males showed that they differ in important ways. (1) The spfash liver contains about 33% more mitochondrial protein per g than does normal liver. (2) The specific activities of carbamoyl-phosphate synthetase (ammonia) and glutamate dehydrogenase are about 15% lower than normal in mitochondria from spfash mice, whereas those of beta hydroxybutyrate dehydrogenase and cytochrome oxidase are 22% higher and 30% lower respectively. (3) In the presence of 10 mM-ornithine and the substrates for carbamoyl phosphate synthesis, coupled and uncoupled mitochondria from spfash mice synthesize citrulline at unexpectedly high rates, about 25 and 44 nmol/min per mg respectively. Though these are somewhat lower than the corresponding rates obtained with normal mitochondria, the difference does not arise from the deficiency in ornithine carbamoyltransferase, but from the lower carbamoyl phosphate synthetase activity of the mutant mitochondria. (4) At lower external [ornithine] (less than 2 mM), a smaller fraction of the carbamoyl phosphate synthesized is converted into citrulline in spfash than in normal mitochondria. These studies show that what appears to be a single mutation brings about major adaptations in the mitochondrial component of liver. In addition, they clarify the role of ornithine transport and of protein-protein interactions in citrulline synthesis in normal mitochondria. PMID- 2920016 TI - The renal Na+/Ca2+ exchange system is located exclusively in the distal tubule. AB - The movement of Ca2+ across the basolateral plasma membrane was determined in purified preparations of this membrane isolated from rabbit proximal and distal convoluted tubules. The ATP-dependent Ca2+ uptake was present in basolateral membranes from both these tubular segments, but the activity was higher in the distal tubules. A very active Na+/Ca2+ exchange system was also demonstrated in the distal-tubular membranes, but in proximal-tubular membranes this exchange system was not demonstrable. The presence of Na+ outside the vesicles gradually inhibited the ATP-dependent Ca2+ uptake in the distal-tubular-membrane preparations, but remained without effect in those from the proximal tubules. The activity of the Na+/Ca2+ exchange system in the distal-tubular membranes was a function of the imposed Na+ gradient. These results suggest that the major differences in the characteristics of Ca2+ transport in the proximal and in the distal tubules are due to the high activity of a Na+/Ca2+ exchange system in the distal tubule and its virtual absence in the proximal tubule. PMID- 2920017 TI - Longer-term regulation of branched-chain-2-oxoacid dehydrogenase complex studied in rat hepatocytes in culture. AB - The effect of protein-free diet to decrease liver activity of branched-chain (-2 oxoacid) dehydrogenase (BCD) complex (active form) and increase BCD kinase activity was unaffected by preparation of hepatocytes, but partially reversed by 25 h of culture of hepatocytes in medium 199. Activation of BCD complex preceded loss of BCD kinase. The effect of culture on BCD complex was completely prevented by omission of branched-chain amino acids and partially prevented by 1 mM-alpha cyano-4-hydroxycinnamate or 0.2 mM-pyruvate/2 mM-lactate. Protein-free diet decreased plasma branched-chain amino and oxo ('keto') acids and increased plasma pyruvate and lactate. It is concluded: (1) that branched-chain amino acids are involved directly in regulation of activities of BCD complex and BCD kinase; (2) that mitochondrial uptake of branched-chain oxo acids is necessary for regulation of BCD complex activity; and (3) that the stable increase in BCD kinase may function as a hysteresis mechanism. PMID- 2920018 TI - Is methionine transaminated in skeletal muscle? AB - Methionine transamination is extensive in rat and chick skeletal-muscle homogenates, but is barely detectable in intact rat, but not chick, skeletal muscles. Branched-chain amino acids essentially block methionine transamination in intact muscles and homogenates from both species. The physiological significance of methionine transamination in skeletal muscle is questioned. PMID- 2920019 TI - Sub-micromolar concentrations of extramitochondrial Ca2+ stimulate the rate of citrulline synthesis by rat liver mitochondria. AB - 1. In the presence of physiological concentrations of Na+ and Mg2+, the rate of citrulline synthesis by isolated rat liver mitochondria respiring on a range of substrates was stimulated by up to 60% when the extramitochondrial Ca2+ concentration was raised from 130 pM to 770 nM. 2. Our findings suggest that hormonal stimulation of the urea cycle may be mediated by Ca2+. PMID- 2920020 TI - Identification of an androgen-repressed mRNA in rat ventral prostate as coding for sulphated glycoprotein 2 by cDNA cloning and sequence analysis. AB - The concentrations of a small number of mRNAs in the rat ventral prostate increase after castration and then decrease upon androgen treatment. Since the repression of specific gene expression may be important in the regulation of organ growth, we have cloned a cDNA for an androgen-repressed mRNA, the concentration of which increased 17-fold 4 days after castration, and this increase was reversed rapidly by androgen treatment. By sequence analysis the androgen-repressed mRNA was identified as that coding for sulphated glycoprotein 2. PMID- 2920022 TI - Some uses of extrapolation in kinetics. AB - Extrapolation procedures are shown to be useful for obtaining kinetic parameters from irreversible enzymic reactions in which there are two intermediates, under both single-turnover and steady-state conditions. Small excesses of one component are treated as if they were large excesses, which is convenient in practice. The method has also been applied to a non-enzymic reversible bimolecular reaction. PMID- 2920021 TI - Binding of various ovotransferrin fragments to chick-embryo red cells. AB - 1. The ability of N- and C-terminal half-molecule fragments of hen ovotransferrin to interact with chick red blood cells (CERBC) has been studied under conditions that allow binding of the transferrin to transferrin receptors to take place, but not the delivery of iron to the cell. Two kinds of half-molecule fragments were used: (a) those which can associate with one another to give a dimer resembling native transferrin and (b) those which cannot associate in this way because they lack a few amino acid residues from their C-terminal ends. 2. Neither N nor C half-molecules alone can bind to the CERBC, but, when both are present, tight binding occurs. 3. Whether or not the half-molecules can associate with one another makes little difference to receptor binding. 4. Given that one of the half-molecules is iron-saturated, the presence or absence of iron in the contralateral half-molecule again makes little difference to receptor binding. PMID- 2920024 TI - Structural and electrostatic differences between actinidin and papain account for differences in activity. PMID- 2920023 TI - The interplay of electrostatic and binding interactions determining active centre chemistry and catalytic activity in actinidin and papain. PMID- 2920025 TI - Type analysis of the oligosaccharide chains on microheterogeneous components of bovine pancreatic DNAase by the lectin-nitrocellulose sheet method. AB - The oligosaccharide chains of microheterogeneous bovine pancreatic DNAases were characterized by the lectin-nitrocellulose sheet method. The active fractions of the DNAases from column chromatography showed four major and several minor spots on a two-dimensional polyacrylamide gel. They were transferred on to nitrocellulose sheets and treated with glycosidases (neuraminidase, endo-beta-N acetyl glucosaminidase H or F, or peptide N-glycosidase F) and treated with peroxidase-coupled lectins (concanavalin A, Ricinus communis agglutinin or wheat germ agglutinin). From the results, the most probable oligosaccharide types were proposed to be as follows: the four major spots contained components which had high-mannose type or hybrid-type oligosaccharides, such as those susceptible to endo-beta-N-acetylglucosaminidase H. In addition, spot 1 contained a complex-type biantennary oligosaccharide without sialic acid and spot 3 contained a tri- or tetra-antennary complex-type oligosaccharide with sialic acid. The component corresponding to spot 2 had a hybrid-type oligosaccharide chain with a 'bisecting' acetylglucosamine, linked 1-4 to the beta-mannose residue of the trimannosyl core, and the component corresponding to spot 4 had a high-mannose type oligosaccharide chain. PMID- 2920026 TI - Partial purification and characterization of a formylmethionine deformylase from rat small intestine. AB - A formylmethionine deformylase from rat small-intestinal mucosa has been isolated, characterized and partially purified. The enzyme catalyses the release of equimolar amounts of formate and the free amino acid. The deformylase was active against formylmethionine (Km 7.1 mM) and formylnorleucine, but showed reduced activity against formyl-leucine. It was inactive against a range of other polar and nonpolar formyl-amino acids and against formyl di- and tri-peptides. The Mr of the native enzyme was between 45,000 and 66,000, as determined by h.p.l.c. gel permeation. Further purification of the enzyme either by h.p.l.c. ion-exchange chromatography and concanavalin A-Sepharose or by isoelectric focusing yielded a preparation with one predominant band of Mr 50,000 on SDS/polyacrylamide-gel electrophoresis. Bacteria in the intestine present the host with substantial amounts of formylmethionine (fMet) from proteinase and carboxypeptidase digestion of bacterial formyl-peptides in the intestinal lumen. fMet (0.01-1.0 mM) inhibited translation of a test RNA from brome mosaic virus in vitro, indicating that it could have adverse effects on cellular metabolism. Gut epithelial fMet deformylase may be required for deformylation of this exogenous (bacterial) and also endogenous (mitochondrial) fMet. PMID- 2920027 TI - A single-parameter family of adjustments for fitting enzyme kinetic models to progress-curve data. AB - Current methods for fitting integrated rate equations to enzyme progress curves treat each observation as if it were an independent measurement. When the data are obtained by taking several successive readings from each of a series of progress curves, the data will not be truly independent and will exhibit autocorrelation. Here we propose a simple pragmatic extension of integrated rate equations which takes account of first-order autocorrelations. The value of the method is assessed when applied to five sets of experimental data. PMID- 2920028 TI - Physiochemical studies on achatininH, a novel sialic acid-binding lectin. AB - We have purified a sialic acid-binding lectin, achatininH, in a single step by affinity chromatography, having high affinity for 9-O-acetylneuraminic acid. The physicochemical characterization of the interaction of achatininH with bivalent metal ions and sialic acid derivatives by the use of spectrofluorimetry, spectropolarimetry and precipitin reaction is reported. From fluorescence quenching studies the binding of Ca2+ (Ka = 251 +/- 9 M-1) and of Mn2+ (Ka = 86 +/- 5 M-1) was found to be weak, but their presence is absolutely necessary for sugar binding as well as biological activity. The nature and position of the substituent group play a very important role in the binding affinity. AchatininH shows a high affinity for 9-O-acetylneuraminic acid (Ka = 1.20 x 10(3) +/- 0.07 x 10(3) M-1) compared with that for the 4-O-acetyl derivative. In oligomers the binding strength increases in the order monosaccharide less than disaccharide less than trisaccharide. The binding affinity of achatininH for the disaccharide was found to reach a peak around pH 8. From c.d. spectral studies achatininH was found to have a high beta-sheet content (46%) and a low alpha-helix content (24%). From precipitin analysis at least one sugar-binding site on each of the 16 monomer subunits of the protein is indicated. PMID- 2920029 TI - Minimum requirements for inhibition of smooth-muscle myosin light-chain kinase by synthetic peptides. AB - Although the amino acid residues that are important for peptide substrates of myosin light-chain kinase have been reported, those that are important for peptide inhibitors of this enzyme have not previously been investigated. Synthetic peptides based on the sequence Lys11-Lys12-Arg13-Ala-Ala-Arg16-Ala-Thr Ser19 -Asn-Val21-Phe22-Ala of the chicken gizzard myosin light chain were tested as inhibitors of pig carotid-artery myosin light-chain kinase. The basic amino acid residues of the known myosin light-chain kinase inhibitor Lys-Lys-Arg-Ala Ala-Arg-Ala-Thr-Ser-NH2 (IC50 = 14 microM) [Pearson, Misconi & Kemp (1986) J. Biol. Chem. 261, 25-27] were shown to be the important residues that contribute to inhibitor potency, as evidence by the finding that the hexapeptide Lys-Lys-Arg Ala-Ala-Arg-NH2 had an IC50 value of 22 microM. This indicates that binding of the phosphorylatable serine residue to myosin light-chain kinase, which is of obvious importance for a substrate, does not enhance the potency of an inhibitor. With the aim of preparing more potent inhibitors, peptides Lys-Lys-Arg-Ala-Ala Arg-Ala-Ala-Xaa-NH2 were prepared with a variety of amino acids substituted for the phosphorylatable serine residue. None of these peptides was a more potent inhibitor than the serine peptide. PMID- 2920030 TI - A type VI collagen-related glycopolypeptide is the major concanavalin A-binding component in pig skin. AB - The major concanavalin A-binding component in urea/deoxycholate/mercaptoethanol extracts of pig skin was a collagenous disulphide-cross-linked glycopolypeptide with an apparent molecular mass of 150 kDa and a pI of 5.5. Antiserum against the electrophoretically purified glycopolypeptide gave strong dermal staining similar to that seen with fluorescent concanavalin A. Immunocytochemical labelling showed prominent labelling of 3-4 nm dermal microfilaments, particularly those associated with dermal blood vessels and mast cells. Immunoblotting with authentic antiserum indicated that the major skin glycopolypeptide was probably identical with collagen-like glycoprotein, the tissue form of the alpha 1/alpha 2 subunits of type VI collagen. This was confirmed by immunoblotting of authentic type VI collagen from pepsin-treated pig skin. Immunoblotting, metabolic labelling with [3H]glucosamine and immune precipitation showed that an immunoreactive collagenous glycopolypeptide was synthesized and secreted by cultured pig skin fibroblasts. The results suggest that type VI collagen is the major concanavalin A-binding component in pig skin. PMID- 2920031 TI - Partial purification of a protein from maize (Zea mays) coleoptile membranes binding the Ca2+-channel antagonist verapamil. AB - A protein that binds the calcium-channel antagonist verapamil has been partially purified from maize (Zea mays) coleoptile membranes. The protein was solubilized with the detergent CHAPS ([ 3-(3-cholamidopropyl)dimethylammonio]propane-1 sulphonate) and purified by a combination of ion-exchange, gel-filtration and hydrophobic-interaction chromatography. This resulted in a 120-fold purification. SDS/polyacrylamide-gel-electrophoretic analysis of the polypeptides from the final purification step indicated that the verapamil-binding protein may have a major component of Mr 169,000. The dissociation constants for specific binding of [3H]verapamil to crude and CHAPS-solubilized maize coleoptile membrane fractions are 72 nM and 158 nM respectively, with respective binding-site concentrations of 135 pmol/mg of protein and 78 pmol/mg of protein. In both cases the Scatchard plots are linear, indicating a single class of binding sites. [3H]Verapamil binding to crude maize coleoptile membrane fractions could not be displaced by unlabelled desmethoxyverapamil or by nifedipine, but could be displaced by unlabelled methoxyverapamil. PMID- 2920032 TI - Na-Ca exchanger as a calcium influx pathway in adrenal glomerulosa cells. AB - When aequorin-loaded glomerulosa cells were incubated in isotonic Na2+-free medium containing N-methyl-D-glucamine instead of NaCl, there was an increase in cytoplasmic free calcium concentration, [Ca2+] c, which was not observed when extracellular calcium concentration was reduced to 1 microM. Upon removal of extracellular sodium, there was nearly five-fold increase in fractional efflux ratio of calcium. The reduction of extracellular sodium resulted in a stimulation of calcium influx rate, the magnitude of which was dependent on extracellular sodium concentration. Similar stimulation of calcium influx was observed when extracellular sodium was replaced with lithium. Nitrendipine did not affect the calcium influx induced by the reduction of extracellular sodium while a derivative of amiloride 3',4'-dichlorobenzamil, which inhibits Na-Ca exchange, attenuated calcium influx observed in sodium-free medium. These results indicate that removal of extracellular sodium leads to an increase in [Ca2+] c by stimulating calcium influx and that calcium enters the cell via Na-Ca exchanger. PMID- 2920033 TI - The role of phospholipase A2 in microsomal lipid peroxidation induced with t butyl hydroperoxide. AB - The role of phospholipase A2 (PlA2) in lipid peroxidation induced with t-butyl hydroperoxide was examined in rat liver microsomes. Exposure of microsomes to t butyl hydroperoxide was associated with activation of endogenous PlA2. When PlA2 was inhibited with chlorpromazine, mepacrine, or p-bromphenacyl bromide, the accumulation of thiobarbituric acid reactive substances (TBARS) was reduced in a dose dependent manner. In contrast, the accumulation of conjugated dienes was not affected by chlorpromazine, and was slightly increased by mepacrine. When endogenous PlA2 was activated with mellitin prior to induction of peroxidation, accumulation of both TBARS and dienes was reduced. Analogously, pretreatment with exogenous PlA2 reduced both dienes and TBARS. In contrast, addition of mellitin following the induction of peroxidation did not alter either TBARS or dienes. PMID- 2920034 TI - Heterobifunctional cross-linking of a monoclonal antibody with 2-methyl-N1 benzenesulfonyl-N4-bromoacetylquinonediimide. AB - The Cyssor reagent, 2-methyl-N1-benzenesulfonyl-N4-bromoacetylquinonediimide, which will cleave a protein chain at Cys under acidic conditions, cross-linked unreduced and partially reduced antibody at pH 8.0. No cleavage of the antibody occurred suggesting that the Cyssor reagent may be useful with certain proteins as a heterobifunctional cross-linker. PMID- 2920035 TI - The amino acid sequence of the chromosomal protein HMG-Y, its relation to HMG-I and possible domains for the preferential binding of the proteins to stretches of A-T base pairs. AB - The primary structure of the human high mobility group (HMG) protein HMG-Y has been established except for a few amino acids in the N-terminal and the C terminal part of the protein. It was found that the sequence was identical to that of HMG-I except for a run of eleven amino acids. Like HMG-I the protein was N-terminally blocked and the palindromic sequence Pro-Arg-Gly-Arg-Pro occurred twice as in HMG-I. The binding of peptides derived from HMG-I (after thermolysin cleavage) to poly (dA-dT).poly(dA-dT) suggested that there are at least two different binding domains in the protein and that binding is not dependent upon an intact protein. PMID- 2920036 TI - Interactions of factors bound at two different sites in the 5'-upstream region of the adenovirus 12 E1A gene. AB - A nuclear extract of Ehrlich ascites tumor cell contains factors binding to two distinct sites in the 5'-upstream region of the adenovirus 12 E1A gene. The gel shift assay was performed for characterization of the binding factors with oligo DNA probes containing sequences corresponding to these sites. The specific binding of a factor to one probe was enhanced when the other oligo DNA was present in excess in the binding reaction. Thus possibly, protein-protein interactions between factors may mutually prevent their binding to target sequences. PMID- 2920037 TI - Structure of mouse fatty acid synthase mRNA. Identification of the two NADPH binding sites. AB - Overlapping cDNA clones corresponding to 3.3 kb covering the carboxy-half and 3' non-coding regions of the single 8.2 kb mouse fatty acid synthase mRNA were isolated and sequenced. The sequence coded for 838 amino acid residues, followed by termination codon TAG, 771 nucleotides of 3' untranslated sequence and a poly A tail. For the first time, the two putative components of the NADPH binding sites of fatty acid synthase were identified, thereby making it possible to assign the enoyl reductase and beta-ketoacyl reductase domains of the multifunctional fatty acid synthase. Overall, the deduced amino acid sequence provides the domains for enoyl reductase, beta-ketoacyl reductase, acyl carrier protein and thioesterase of the mouse fatty acid synthase. PMID- 2920038 TI - Zero-field Mossbauer studies of diferric human transferrin. AB - Diferric transferrin samples labelled with 57Fe at the N- or the C-terminal binding sites are compared by Mossbauer spectroscopy at 15 K and in zero magnetic field. The spectra of the samples are similar but the fitting of single Lorenzian lines to the data shows that some of the line positions differ in the two cases. According to this we can not exclude a difference between the chemical structures of the binding sites that can arise for example from the participation of different forms of the anion and/or water in the two lobes of transferrin. All other line parameters (line-width, intensity) are the same within the limits of errors. PMID- 2920039 TI - Molecular cloning of the human transmembrane secretory component (poly-Ig receptor) and its mRNA expression in human tissues. AB - A 2.5 kilobase (kb) cDNA clone containing 92% of the coding region for human transmembrane secretory component (SC) or poly-Ig receptor, was isolated from a mammary gland cDNA library. The cDNA clone encoded a protein of 693 amino acids which showed 99% homology with the primary amino acid sequence of human free SC as reported by Eiffert et al. (1), and 54% homology with the deduced amino acid sequence of rabbit transmembrane SC for which cDNA was cloned by Mostov et al. (2). Northern blot analysis showed mRNA expression in various human exocrine tissues in good agreement with our previous immunohistochemical studies of SC. PMID- 2920040 TI - Association of endogenous synenkephalin containing peptides with intracellular membranes of bovine adrenal medulla. AB - The association of endogenous synenkephalin and met-enkephalin containing peptides with the membrane of bovine chromaffin granules and physicochemical characteristics of this association were studied. The associated materials were only released at a non physiological pH range and this effect was enhanced with growing salt concentrations (0.5, 1.0 and 2.0 M KSCN). A higher peptide dissociation occurred with membrane solubilizing agents (SDS greater than Triton X-100 greater than digitonin). In microsomes the materials dissociated with 2 M KSCN (pH 7.4) corresponded to peptides larger than 12.0 kDa, while in granules corresponded to molecules smaller than 8.5 kDa, displaying synenkephalin and met enkephalin immunoreactivities. These data suggest that some sequence of the C terminal portion of synenkephalin may be responsible for the association of proenkephalin derived peptides with microsome and granule membranes. PMID- 2920041 TI - Activation of the bone-derived latent TGF beta complex by isolated osteoclasts. AB - Although TGF beta is unquestionably an important growth regulatory polypeptide with effects on many cell types, the cellular mechanisms which release it from the binding proteins which mask its biological activity are not well understood. Here we show that when isolated osteoclasts are activated, they release active TGF beta from the latent TGF beta complex produced by bone organ cultures. Since active TGF beta has powerful inhibitory effects on osteoclast formation and bone resorption and stimulates osteoblast activity, is present in abundant amounts in the bone matrix and is released during hormone-stimulated osteoclastic bone resorption, the activation of TGF beta by stimulated osteoclasts may be an important regulatory step in normal bone remodeling. PMID- 2920042 TI - Preferential cleavage of amino- and carboxyl-terminal oligopeptides from vasoactive intestinal polypeptide by human recombinant enkephalinase (neutral endopeptidase, EC 3.4.24.11). AB - Human recombinant enkephalinase (neutral endopeptidase, EC 3.4.24.11) cleaved synthetic vasoactive intestinal peptide (VIP1-28) with time-and peptidase concentration-dependence, which left less than 30% intact after 30 micrograms was incubated at 37 degrees C with 0.1 micrograms and 10 micrograms of peptidase for 120 min and 15 min, respectively. The rank order of relative rates of peptidolysis amino-terminal to hydrophobic amino acids was Ala4 and Val5 greater than Tyr22 and Ile26 much greater than Leu13 and Met17. The many effects of VIP1 28 on epithelial cell and leukocyte functions thus may be influenced by degradation of the mediator by enkephalinase at the surface of target cells. PMID- 2920043 TI - Secretagogue induced calcium mobilization in single pancreatic acinar cells. AB - Microspectrofluorometry of fura-2 was utilized to monitor [Ca2+]i in single acinar cells stimulated with a cholinergic agonist and cholecystokinin. A similar amplitude of agonist induced Ca mobilization between single cell and populational approaches was observed. New findings in single cells not observable in populations of cells include: 1) the maintenance of a sustained elevation in [Ca2+]i above basal levels throughout agonist application, 2) the reloading of the agonist-sensitive Ca pool only following removal of the agonist and 3) the presence of oscillations of [Ca2+]i in response to agonist application which is enhanced at lower agonist concentrations. PMID- 2920044 TI - Activation of human neutrophil NADPH-oxidase in vitro by the catalytic fragment of protein kinase-C. AB - Phorbol ester treatment of intact neutrophils both stimulates protein kinase C (PK-C) and causes the rapid proteolytic conversion to a cytosolic, co-factor independent fragment, protein kinase M (PK-M). In intact neutrophils, phorbol ester treatment activates the NADPH-oxidase, the enzyme responsible for the oxidative burst. Addition of purified PK-M to resting neutrophil light density membranes activated the NADPH-oxidase in the presence of PS, ATP and Mg2+. A 3.5 fold greater stimulation of oxidase (ca. 25 nmoles O2-/min/mg membrane protein) was obtained with comparable PK-M concentrations to that observed with the reconstituted PK-C system, and approximately 1/3 that obtained with arachidonic acid (AA) or SDS. In contrast to the reconstituted system using PK-C, PMA and Ca++ were neither required nor affected activity. The effect of PS was unexpected, since PK-M does not require phospholipids for enzymatic activity, and likely represents the action of PS on the oxidase itself or on another component in the plasma membrane fraction. Our studies demonstrate for the first time that purified PK-M permits reconstitution of a physiologic phorbol ester response. PMID- 2920045 TI - Magnesium-dependent non-specific binding of [125I]prolactin to myelinated tracts in the rat central nervous system. AB - An in vitro autoradiographic assay was used in identifying a magnesium-dependent, non-specific binding of [125I] prolactin to myelinated fiber tracts in the rat brain. Frozen tissue sections were incubated for 18 h at 4 degrees C in media which included [125I]prolactin alone or with a 500 fold excess of unlabelled prolactin. Magnesium in the incubation medium caused a non-specific binding of radiolabelled prolactin to the myelinated fiber tracts in the brain. In contrast, calcium did not facilitate prolactin non-specific binding to myelin. Hence, calcium should optimize the detection of specific prolactin binding sites in the brain by in vitro autoradiographic or radioreceptor assays. PMID- 2920046 TI - The nucleotide sequence of a full length cDNA clone encoding rat liver urate oxidase. AB - Recently we reported the sequence of a cDNA clone (pUOX-1), isolated from a lambda gt11 cDNA library, which encoded for rat liver urate oxidase (EC 1.7.3.3), but this clone lacked the nucleotide sequences encoding the N-terminal region for this enzyme. Using the cDNA insert from the pUOX-1 clone as a probe, we have now isolated a full length cDNA clone, pUOX-2, from a lambda gt10 library by plaque hybridization. Nucleotide sequence analysis of the pUOX-2 clone showed that it has 1379 base pairs with an open reading frame coding for 303 amino acid residues corresponding to a molecular mass of 34,931 daltons. In addition to the open reading frame the pUOX-2 contains 439 bp of 3'-untranslated and 41 bp of 5' untranslated sequences. The consensus polyadenylation signal AATAAA precedes a stretch of poly(A)+ residues at the 3' end. PMID- 2920047 TI - Liver histology in rheumatoid arthritis patients receiving long-term methotrexate therapy. A prospective study with baseline and sequential biopsy samples. AB - Twenty-nine patients with active rheumatoid arthritis receiving long-term oral weekly methotrexate (MTX) therapy were studied to determine the extent of their hepatic architectural changes. Liver biopsies (n = 101) were performed in all patients before the initiation of MTX therapy, after 2 years, and annually thereafter (mean duration of therapy 53 months). The hepatic histologic grade (5 point scale) in 25 patients increased (worsened) (mean +/- SEM change 0.84 +/- 1.02; P = 0.001). Fibrosis, confirmed by trichrome staining, developed in 14 of 27 patients (52%). A history of alcohol consumption prior to starting MTX correlated significantly with subsequent worsening of the liver biopsy grade (r = 0.55, P = 0.0054). Alcohol intake prior to study entry, elevated weight at MTX initiation, and dose and duration of MTX were significantly associated with the development of fibrosis. Elevations in serum aspartate aminotransferase levels at 29-53 months of therapy correlated with the increase in hepatic histologic grade at the 3-year biopsy (r = 0.50, P = 0.04) and 4-year biopsy (r = 0.58, P = 0.03). We conclude that long-term MTX therapy in rheumatoid arthritis patients results in a statistically significant worsening in hepatic histologic grade, with common development of mild fibrosis. We do not consider these changes to be clinically significant at present. PMID- 2920048 TI - Lack of correlation between the Steinbrocker staging of hand radiographs and the functional health status of individuals with rheumatoid arthritis. AB - We evaluated the correlation between destructive changes seen on hand radiographs and disability in 54 patients with definite or classic rheumatoid arthritis. No statistically significant correlation was found between radiographic findings and patient disability as determined by patient and physician assessment or by the patient's score on the Arthritis Impact Measurement Scales questionnaire. These findings call into question the appropriateness of using hand radiographs as a determinant of disability or as a criterion for disability insurance benefits. PMID- 2920049 TI - Demonstration of a cross-reactive idiotype (IdRQ) in rheumatoid factors from patients with rheumatoid arthritis but not in rheumatoid factors from healthy, aged subjects. AB - A human monoclonal IgM kappa paraprotein with rheumatoid factor (RF) activity was used to elicit antiidiotypic antibodies in rabbits. The antiidiotypic antiserum thus obtained reacted with samples from 40% of 72 rheumatoid arthritis patients, but not with any of the samples from 22 aged control subjects having serum RF. Our findings suggest that, despite the similarities between RF from rheumatoid arthritis patients and that from healthy individuals, the expression of V region genes may be different in healthy subjects and those with the disease. PMID- 2920050 TI - Tumor necrosis factor in the serum of patients with systemic lupus erythematosus. AB - In view of recent data demonstrating defective production of tumor necrosis factor alpha (TNF cachectin) in murine autoimmune lupus nephritis, we studied the serum levels of TNF in 22 patients with systemic lupus erythematosus (SLE), using a specific radioimmunoassay. Patients with SLE had either normal or slightly elevated levels of TNF when compared with healthy control subjects. All 5 SLE patients with concomitant infections had elevated levels of TNF; those with systemic bacterial infection had markedly raised levels (median 260 pg/ml; normal less than 40). These results show that SLE in humans is not associated with a depressed level of circulating TNF, and that in SLE patients with infection, the level of TNF in the circulation increases in a manner similar to that in other subjects. PMID- 2920051 TI - Pregnancy in women with systemic sclerosis. AB - We assessed fetal morbidity and mortality in women with systemic sclerosis (SSc). Women with a history of SSc and a concomitant pregnancy completed a detailed questionnaire about the pregnancy. These 48 subjects were age-matched and race matched to 2 other groups of women (a rheumatoid arthritis group and a control group from the same neighborhood), all of whom had been pregnant at least once. There were no differences in the frequencies of miscarriage or perinatal death in the SSc group compared with the 2 control groups. Preterm births occurred slightly more frequently in both SSc patients and rheumatoid arthritis patients compared with the neighborhood control subjects. There were significantly more small full-term infants born to women with SSc. Interestingly, the increase in preterm births and small full-term babies occurred with equal frequency prior to and after the onset of disease. Although close monitoring for premature birth and intrauterine growth retardation is necessary, we conclude that an uneventful, healthy pregnancy is possible for women with SSc. Those with early, rapidly progressive, diffuse skin thickening should avoid becoming pregnant since, intrinsically, they are at higher risk of developing renal crisis. PMID- 2920052 TI - Does smoking protect against osteoarthritis? AB - While studying knee osteoarthritis (OA) in the first Health and Nutrition Examination Survey, we unexpectedly found a protective association between smoking and OA. After adjustment for age, sex, and weight, smokers had a significantly lower rate of OA than did nonsmokers, and heavier smokers were less likely to have the disease than were light smokers. To test this association in a separate study and see if it was due to confounding factors, we looked at the Framingham Osteoarthritis Study, a study of elderly members of the Framingham Heart Study cohort. We evaluated whether the presence of knee OA in 1983-1985 was related to smoking status at the first Framingham examination, 36 years earlier. Subjects who had been smokers at examination 1 had a lower rate of OA (190 of 679, 28%) than did nonsmokers (276 of 736, 37.5%). In an analysis adjusted for age, sex, and weight, heavy smokers had a modestly lower risk of developing knee OA than did nonsmokers (relative risk 0.81). Also, the adjusted risk of severe OA was less in heavy smokers than in nonsmokers (relative risk 0.73). The negative association with OA persisted when we examined the average cigarette consumption over the first 10 years of the Framingham study. Furthermore, after controlling for age, sex, weight, knee injury history, sports activity history, physical activity level, coffee and alcohol consumption, and weight change after examination 1, and after modeling weight and age in a nonlinear manner, smoking remained a significant protector against later knee OA. It appears that smoking or some unidentified factor correlated with smoking modestly protects against the development of knee OA. PMID- 2920053 TI - Protective effects of corticosteroids on cartilage lesions and osteophyte formation in the Pond-Nuki dog model of osteoarthritis. AB - The in vivo effects of corticosteroids on osteoarthritic (OA) lesions were examined in 12 dogs in which the anterior cruciate ligament had been sectioned. Six were treated with oral prednisone and 6 were treated with intraarticular (IA) injections of triamcinolone hexacetonide (TH), at surgery and 4 weeks later. Twelve other operated dogs received no treatment. All dogs were killed 8 weeks postsurgery. Four of 15 normal control dogs received IA TH injections. Operated untreated dogs developed significant cartilage lesions on the femoral condyles and tibial plateaus with prominent osteophytes. Operated dogs treated orally or with IA injections had a significant reduction in osteophyte size. Cartilage erosions on femoral condyles were observed in 25% of the untreated dogs, 8% of the dogs receiving oral prednisone, and none of the dogs receiving IA TH. In both groups of treated dogs, the size of the tibial plateau lesions was significantly reduced compared with the operated untreated dogs. Histologically, corticosteroids significantly reduced the severity of OA structural changes of the cartilage on both medial and lateral femoral condyles and tibial plateaus in operated animals, with the exception of the lateral plateaus of those treated orally. In electron microscopy studies, we found no evidence of increased cell degeneration or death associated with steroids. IA corticosteroids had no deleterious effects on normal articular cartilage. These results indicate that glucocorticoids administered orally or intraarticularly are effective against the development of OA lesions in this model. PMID- 2920055 TI - The "neck sign" in scleroderma. AB - The "neck sign" consists of ridging and tightening of the skin of the neck on extending the head. In this study it was found to be positive in over 90% of patients with scleroderma and negative in patients with primary Raynaud's disease and in control subjects. It is a useful diagnostic test for scleroderma. PMID- 2920054 TI - Reversal of neutropenia with methotrexate treatment in patients with Felty's syndrome. Correlation of response with neutrophil-reactive IgG. AB - We evaluated the clinical and hematologic response to methotrexate (MTX) in 4 women with Felty's syndrome (FS) who had had neutropenia for 1-3 years. Since immune complexes or antineutrophil antibodies are implicated in the pathogenesis of the neutropenia of FS, we also measured both direct and indirect levels of neutrophil-reactive IgG. All 4 patients showed a prompt and dramatic increase in neutrophil counts within 1-2 months of starting MTX therapy. In 3 patients, the symptoms of arthritis also improved; in the fourth patient, arthritis worsened. Recurring infections ceased in 3 patients. Neutrophil-reactive IgG levels, which were elevated in all patients prior to treatment, decreased toward normal while the patients were receiving MTX therapy. We conclude that MTX is effective in treating the neutropenia of FS, in part by lowering neutrophil-reactive IgG. PMID- 2920056 TI - Central nervous system vasculitis in Behcet's syndrome: angiographic improvement after therapy with cytotoxic agents. AB - We describe a patient with Behcet's syndrome who had clinical and angiographic features of widespread cerebral angiitis of small- and medium-caliber vessels. We report the successful treatment of this condition with a combination of cytotoxic agents and steroids, and demonstrate angiographically the resolution of these abnormalities in neuro-Behcet's disease. PMID- 2920057 TI - Favorable results using methotrexate in the treatment of patients with ankylosing spondylitis. PMID- 2920058 TI - Thrombocytopenia in patients with Sjogren's syndrome. PMID- 2920059 TI - Comment on the article by Tomana et al. PMID- 2920060 TI - Chronic fungal olecranon bursitis caused by Penicillium. PMID- 2920061 TI - Freeze-fracture study of the intramembrane particle density in the aortic smooth muscle cell plasmalemma of rabbits fed an atherogenic diet. AB - The density of intramembrane particles (IMP) of the arterial smooth muscle cell (SMC) plasmalemma was studied by freeze-fracture methods in rabbits fed an atherogenic diet. After 3 weeks of diet, no change in the IMP E face density was observed but the IMPs of the P face decreased by about 50%. Among the various functions of IMPs, they are also believed to be responsible for mechanical adhesion between adjacent cells and cell-cell interactions. That is why the modification of their frequency observed in this study may be assumed to induce the non-recognition of SMC between each other. Thus, they become free from each other and migrate into the subendothelial space. This is one of the important initial conditions leading to atherosclerosis. Therefore, by this freeze-fracture study, our hypothesis about the involvement of SMC in the earlier stages of atherogenesis is confirmed. PMID- 2920062 TI - Increased urinary mevalonic acid excretion in patients with abetalipoproteinemia and homozygous hypobetalipoproteinemia. AB - Previous reports in which cholesterol homeostasis has been examined in patients with phenotypic abetalipoproteinemia have shown an increase in whole body cholesterol synthesis when measured by sterol balance techniques but normal rates of cholesterol synthesis when measured by isotopic cholesterol turnover. Recent studies have indicated that increases in cholesterol biosynthesis are paralleled by increases in the plasma concentrations of mevalonic acid and by higher rates of excretion of mevalonic acid in the urine. In the present report we have measured the 24-h urinary excretion of mevalonic acid in 7 patients with phenotypic abetalipoproteinemia and compared this to control subjects. Urinary excretion of mevalonic acid was significantly higher in the patients with abetalipoproteinemia (57.2 +/- 10.2 nmol/kg body weight per day, mean +/- SEM) as compared to control subjects (23.1 +/- 1.5 nmol/kg per day). The magnitude of the increase in urinary mevalonic acid excretion seen in patients with abetalipoproteinemia (148%) is greater than the increase in whole body cholesterol biosynthesis assessed by sterol balance techniques (57% increase). Our results serve to further validate the usefulness of urinary mevalonate as an indicator of relative rates of cholesterol biosynthesis in humans and suggest that this measurement provides a valuable means to potentially screen for disorders associated with an oversynthesis of cholesterol. PMID- 2920063 TI - Change in chromatin organization of the 3'-flanking region of the rat apoprotein E gene in neonatal rats after an increase in transcriptional activity. AB - To investigate if a change in chromatin organization is associated with the increased transcriptional activity of the apoprotein E (apo E) gene, a study was done in hepatic nuclei isolated after birth to identify areas in or flanking the rat apo E gene with increased sensitivity to DNase I. An area of preferential digestion in the 3'-flanking region of the apo E gene was identified in liver nuclei from 3-day-old pups but not in nuclei from fetal livers collected at day 20 of gestation. This hypersensitive area may contain information important for the regulated expression of the rat apo E gene. PMID- 2920064 TI - Modification of lipoprotein patterns and retardation of atherogenesis by a fish oil supplement to a hyperlipidemic diet for swine. AB - We have studied the effect of addition of 30 ml cod liver oil (FO) daily to a highly atherogenic butter (BT) diet for swine on lesion development in the coronary arteries and aorta, plasma lipoprotein (LP) patterns, plasma levels of thiobarbituric acid-reactive substances (TBARS) and on tritiated thymidine labeling indices ([3H]TdR LI) of smooth muscle cells (SMC) and monocyte/macrophages (M/M phi) in the atherosclerotic lesions. Seventeen male Yorkshire swine (11.1 +/- 0.4 kg) were divided into 3 groups: BT (n = 6), BT + FO (n = 6) and mash (n = 5). They were fed the respective diets for 4 months. Terminally, fasting plasma was obtained and cholesterol contents were determined in various fractions of lipoproteins separated by density gradient ultracentrifugation, Pevikon block electrophoresis and immunoelectrophoresis. Apoprotein (B, A-I, E and C) contents of the plasma and lipoprotein fractions were determined by polyacrylamide gel electrophoresis and densitometry of gels stained with Coomassie blue. Swine were injected intramuscularly with 0.5 mCi/kg of [3H]TdR 2 h before death. The aorta and coronary arteries were perfusion fixed in situ under anesthesia. Samples were obtained for microscopic morphometry, autoradiography and immunohistochemistry from distal abdominal aorta, thoracic aorta, and proximal coronary arteries; left main (LM), left anterior descending (LAD), left circumflex (LCX), right main (RM), and right coronary artery (RCA). On the BT diet without FO there was extensive atherosclerotic (AS) lesion development, which was drastically reduced by the addition of FO to the BT diet in all sites by from 71 to 94%. The overall plasma cholesterol (CH) levels were reduced only modestly by the FO (816 +/- 64 to 629 +/- 14 mg/dl) but the distribution of CH in the various lipoprotein classes was remarkably altered. The CH in the large lipoprotein molecules containing both B and E apoproteins was reduced from 488 +/- 84 to 204 +/- 17 mg/dl by the FO with an almost corresponding increase in the conventional LDL molecules containing apo B only (158 +/- 29 to 344 +/- 15 mg/dl). We offer the hypothesis that the large apo B,E containing molecules are much more atherogenic than the smaller apo B containing molecules. This hypothesis is supported by a highly significant correlation between extent of lesion development in all arterial sites and plasma levels of CH in apo B,E containing lipoproteins. Plasma TBARS were elevated by the BT + FO diet but seemed to have no significant effect on the lesions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2920065 TI - Platelet function and survival in rats with genetically determined hypercholesterolaemia. AB - Platelets from rats with genetically determined hypercholesterolaemia are hypersensitive to aggregation induced by thrombin compared with platelets from their genetic controls without hypercholesterolaemia. Aggregation or release induced by thrombin of platelets from hypercholesterolaemic and control rats correlated significantly with plasma cholesterol concentrations. Platelet responses to ADP or collagen were not different between the groups. The hypersensitivity to thrombin-induced aggregation was independent of released ADP or products of arachidonic acid metabolism. The changes in platelet sensitivity occurred with only moderate increases in plasma cholesterol concentration and with no detectable changes in total platelet cholesterol. The hypersensitivity of platelets from hypercholesterolaemic rats was not associated with a reduction in platelet survival or any significant injury to the aortic endothelium in these animals. Platelets from hypercholesterolaemic rats were smaller than platelets from controls. Thus, platelets from rats with genetically determined hypercholesterolaemia have alterations in function similar to those found with platelets from rats with diet-induced hypercholesterolaemia indicating that this strain can be used to study the mechanisms by which cholesterol can change platelet function without the possible complicating effects of dietary factors. Since platelet hypersensitivity occurred in rats with genetically determined hypercholesterolaemia without a reduction in platelet survival, these studies are also consistent with the reduced platelet survival found in animals with diet induced hypercholesterolaemia being independent of platelet changes. PMID- 2920066 TI - Guar gum and gemfibrozil--an effective combination in the treatment of hypercholesterolaemia. AB - Twenty-nine hypercholesterolaemic patients, treated for one year with gemfibrozil but being still hypercholesterolaemic (serum total cholesterol greater than or equal to 6.25 mmol/l) were included in a double-blind trial to evaluate the hypocholesterolaemic effects of gemfibrozil-guar gum combination (GE + GU) vs. gemfibrozil-placebo combination (GE + PL) using a cross-over study design. The patients were treated with gemfibrozil on a constant dosage (range 900-1200 mg/day) during the entire trial. After a 4-week run-in period on GE + PL treatment the patients were randomly allocated to 2 groups: one received GE + GU 15 g/day, and the other GE + PL for 3 months and after that groups were crossed over. Guar gum and placebo were administered as granules taken 3 times a day during meals. Serum total cholesterol was 8.61 +/- 0.17 mmol/l before gemfibrozil therapy, and 7.29 +/- 0.15 mmol/l at the end of the run-in period on GE + PL (P less than 0.01). During the double-blind phase serum total cholesterol values were 6.28 +/- 0.19 mmol/l at the end of the GE + GU treatment period and 7.21 +/- 0.16 mmol/l at the end of the GE + PL treatment period (P less than 0.01). At the end of the GE + GU treatment period serum total cholesterol was 27% lower and LDL cholesterol 39% lower than before gemfibrozil treatment. A marked improvement (23%) was found in HDL/LDL ratio during GE + GU treatment compared with GE + PL treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2920067 TI - Does platelet aggregation play a role in the reduction in localized intimal proliferation in normolipidemic pigs with fixed coronary artery stenosis fed dietary fish oil? AB - In order to investigate the effect of fish oil on intimal proliferation of coronary arteries with a fixed stenosis normolipidemic piglets received a basic diet to which either 9% (w/w) lard (L, n = 8) or 4.5% (w/w) lard and 4.5% (w/w) mackerel oil (ML, n = 8) was added for 4 months. Stenosis was applied by implanting a 4.0 X 2.0 mm (i.d.) Teflon constrictor around the left anterior descending coronary artery (LADCA) (o.d. 2.7 +/- 0.1 mm). During the dietary period ADP-induced platelet aggregation in whole blood was higher in L than in ML. Partial replacement of 20:4 n - 6 by 20:5 n - 3 fatty acids in the platelet membranes of ML may have altered platelet aggregation by changes in eicosanoid synthesis. The plasma cholesterol and triglyceride levels did not change in L, but decreased in ML. At the end of the 4-month dietary period the animals were again anesthetized and regional myocardial perfusion (radioactive labelled microspheres) and systolic segment length shortening (SLS) were measured while the hearts were paced at 160 pulses/min. Perfusion and SLS of non-LADCA nourished segment were similar for L and ML. However, transmural flow to the LADCA perfused myocardium was impaired in both groups, but the deficiency in endocardial perfusion was considerably larger in L than in ML, resulting in a larger loss of SLS in the former. Remote (2-3 cm from the site of the constrictor) luminal encroachment was minimal (less than 2%) in both groups, but at the site of the constrictor there was significant encroachment in both groups which was higher in L (62 +/- 7%) than in ML (11 +/- 4%). It is thought that in these normolipidemic pigs the reduction in platelet aggregation may play a role in the smaller intimal proliferation of the fish oil-fed animals. PMID- 2920068 TI - High density lipoprotein metabolism in a rabbit model of hyperalphalipoproteinemia. AB - The potential utility of an animal model of hyperalphalipoproteinemia for examining the role of high density lipoprotein (HDL) in atherogenesis prompted the current studies. Preliminary data indicated that in rabbits high-coconut oil feeding for 30 days doubled plasma HDL-cholesterol levels, but did not affect lower density lipoproteins (LDL) (d less than 1.063 g/ml). Experiments were performed to examine the composition of these HDL and to determine the mechanism for the diet-induced increase in plasma HDL. Rabbits were fed commercial chow or chow plus 14% (w/w) coconut oil and blood samples were collected 18 h after feeding. Compared to chow-fed rabbits, peak levels of HDL-cholesterol were attained within 2 weeks, and coconut oil feeding doubled the plasma levels of HDL cholesterol, phospholipids and protein for up to 4 months without affecting HDL lipid and apoprotein composition. After 3 months the diet also increased VLDL- (107%) and LDL-cholesterol (40%) levels, but the absolute increases in each of these lipoprotein fractions was less than half of that of HDL. Isotope kinetic studies of 125I-HDL protein indicated a doubled rate of production of HDL and no change in the efficiency of removal of HDL from plasma. These studies demonstrate that in the rabbit high-coconut oil feeding doubles the rate of production and turnover of apparently normal HDL particles. It is proposed that such an animal model could be utilized to examine directly the role of HDL in atherogenesis. PMID- 2920069 TI - Screening for alcohol related problems in the antenatal clinic; an assessment of different methods. AB - This paper assesses different methods of asking about alcohol consumption in the antenatal clinic. Reliable screening methods are essential if appropriate intervention is to be accurately targeted. Women attending antenatal clinic for the first time were questioned about their alcohol consumption in the period immediately before confirmation of pregnancy. Quantity-frequency questions, a question about bingeing and the Cage Questions were asked as part of the routine clinical history by the interviewing doctor. In addition, the women were given a further self-completed questionnaire which contained more detailed questions about the usual quantity and frequency of drinking beers, wines and spirits, the Cage Questions again and the Brief Michigan Alcoholism Screening Test (BMAST). Asking simple quantity-frequency questions coupled with a question about bingeing during the clinical history was shown to be a quick and efficient method of estimating alcohol intake. Self-administered questionnaires were shown to be unnecessary and although the Cage Questions performed better than the BMAST, these alcoholism screening tests were found to be unreliable in this population in which drinking was generally at a low level. PMID- 2920070 TI - Alcoholism, alcohol and attempted suicide. AB - Attempted suicide patients referred to a general hospital over a 10 year period were studied with regard to alcoholism and drinking in association with suicide attempts. Alcoholism was diagnosed in 7.9% of patients (14.6% of males and 4.2% females), and this diagnosis became proportionately more common in both sexes during the study period. However, only male alcoholic attempters showed an increase in absolute numbers during the study period, the increase in the proportion of females diagnosed as alcoholic being due to a decline in attempts by non-alcoholics. Particularly high rates of alcoholism were found in the unemployed of both sexes and in housewives. Alcoholic attempters were at greatly increased risk of making repeat attempts. Alcohol consumption shortly before a suicide attempt and as part of the act was extremely common, especially among alcoholics. In addition to increasing the likelihood of an attempt, alcohol may add considerably to the danger of overdoses. Careful investigation of drinking patterns should be an integral part of the assessment of all attempted suicide patients, and there should be close liaison between general hospital services for such patients and local alcoholism treatment services. PMID- 2920071 TI - Effect of acute ethanol ingestion on human gastric luminal prostaglandin E2, prostaglandin F2 alpha and 6-keto-prostaglandin F1 alpha. AB - In healthy human volunteers we evaluated the effect of a single oral dose of 1 g/kg of alcohol (12.5%, v/v) on the output of prostaglandin E2, prostaglandin F2 alpha and 6-keto-prostaglandin F1 alpha in the gastric juice. In control experiments performed at intervals of 5-8 days, the subjects received the identical volume of water. Ninety minutes after the ingestion of alcohol, or water, first the basal secretion and subsequently the secretion after injection of pentagastrin (6 micrograms/kg, i.m.) were collected over periods of 60 min. The concentrations of the three prostaglandins were determined by radio immunoassay. After ingestion of alcohol, the volume of gastric juice in response to pentagastrin stimulation was reduced by 24.6%, as compared with the control period. Ingestion of alcohol led to a significant reduction in the concentration of prostaglandin E2 (-42.7%) after stimulation with pentagastrin. The prostaglandin E2 output per hour was markedly inhibited by the ingestion of alcohol, both in the basal period (-47%) and after stimulation with pentagastrin (-55%). While stimulation with pentagastrin did not influence the secretion of PGE2 or PGF2 alpha, the output of 6-keto-PGF1 alpha increased appreciably (+88%) after the administration of pentagastrin. Alcohol also significantly (-28%) inhibited the secretion of 6-keto-PGF1 alpha in the period following the administration of pentagastrin. It is supposed that the inhibition of the secretion of prostaglandin E2 and 6-keto-prostaglandin F1 alpha by acute alcohol ingestion, might be of significance for the development of alcohol-induced mucosal damage in the stomach. PMID- 2920072 TI - Alcohol consumption in Guadeloupe. AB - This study bears upon the patterns of alcohol consumption in Guadeloupe (French West Indies), and has been carried out over a representative sample of adults. Each subject was questioned about his or her consumption of alcoholic drinks and a blood sample taken to measure the biological indicators of chronic alcohol consumption. The resulting mean consumption has permitted Guadeloupeans to be classed among the world's foremost consumers of alcohol. For almost half of the adult population, this consumption takes place on a daily basis and therefore constitutes part of everyday life. The patterns of alcohol consumption are linked to sex, age, level of education, employment and socio-professional categories. The heavy-drinking man tends to be elderly, has a low level of education and is an agricultural worker; his consumption is based on rum. The woman is middle-aged and not working; her consumption is based on wine. These stated characteristics permit the setting up of tailored prevention programs. PMID- 2920073 TI - Patient use of treatment options at an ATU and ratings of their relative usefulness. AB - A sample of new patients attending an ATU was followed up for 6 months. All those who had completed at least 3 months of treatment were asked about the kinds of treatment they had received and their views about the usefulness of the various treatment options available (as were staff). Treatment outcome was assessed in terms of drinking behaviour and patient ratings of the severity of their drinking problem. The survey showed considerable variation in the intensity of treatment received; overall the cohort reduced their alcohol consumption substantially (particularly those who received more intensive treatment) and believed their drinking problem to be much less serious. Patient (and staff) views of the various treatment options are presented and discussed. Although staff and patients differed substantially in their views both groups showed little support for the involvement of relatives in treatment. PMID- 2920074 TI - Incidence of cervical spine injuries in association with blunt head trauma. AB - To establish an incidence of cervical spine injuries in significant blunt head trauma and to evaluate the necessity of using cervical radiography, all consecutive cases of blunt head trauma admitted to the trauma service over a 7 month period were reviewed. Two hundred twenty-eight charts were reviewed for demographic information, circumstance of injury, complaints and physical findings referable to the cervical spine, presenting level of consciousness, severity of head injury, and cervical spine radiographic findings. Only three patients were found to have cervical spine injuries, for an incidence of 1.7%. Of the 122 alert and asymptomatic patients, none had cervical spine injury. The patient population was defined, yet the very low incidence of cervical spine injuries associated with blunt head trauma in this study precludes any identification of predictors. Nevertheless, the results suggest that alert and asymptomatic patients can be spared cervical spine radiography. PMID- 2920075 TI - Training lay persons to use automatic external defibrillators: success of initial training and one-year retention of skills. AB - This study was conducted to determine the feasibility of recruitment of lay persons to use automatic external defibrillators (AEDs), the effectiveness of their initial training, and the need for and frequency of retraining over time. Volunteers (n = 146), recruited from a variety of settings, included security personnel and administrative staff from large corporate centers, supervisors from senior care and exercise facilities, and employees in high-rise office buildings. Seven sites for 14 AEDs were recruited. In a single, two-hour class, participants learned to identify and respond to cardiac arrest, to notify emergency personnel, to retrieve and attach the semiautomatic (shock advisory) AED, and to respond to instructions presented on the display screen of the device. A skills check list was used to grade each student on performance of cardiopulmonary resuscitation, operation of the device, and time required to deliver an electric countershock. Retesting was performed one or more times after initial training to assess skill retention. The study lasted 1 year. All age groups, both sexes, and each responder type easily learned to operate the AED, with a trend for lower performance scores in people aged greater than 60 years. Performance time and skills declined significantly after initial training, but returned to satisfactory levels after one retraining session and were even higher after two retraining sessions. With retesting, errors that would have prevented delivery of countershocks to patients in ventricular fibrillation were rare (six of 146 tests, 4%). During the year of this study only three cardiac arrests occurred in the study sites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2920076 TI - A comparison of oral, rectal, and tympanic membrane-derived temperature changes after ingestion of liquids and smoking. AB - Ambulatory patients frequently ingest liquids or smoke just before temperature measurement. The change in body temperature measurements over time following ingestion of ice water, hot water, and smoking were investigated. Twenty-two healthy, afebrile study subjects sequentially ingested temperature-controlled water and smoked a cigarette. Simultaneous oral and auditory canal temperatures were measured over 15 minutes following ingestion. Auditory canal temperatures were obtained with an infrared detection probe; we designated this process a tympanic membrane-derived (TMD) temperature. To determine the correlation between rectal and TMD temperatures, 100 patients had simultaneous measurements at both sites. Mean initial temperatures were rectal, 37.1 +/- 0.5 degrees C (mean +/- S.D.); oral, 36.4 +/- 0.4 degrees C; and TMD, 37.4 +/- 0.4 degrees C. Maximal mean oral temperature change was greatest at 1.5 minutes after hot, +0.9 +/- 0.1 degrees C, and cold, -1.2 +/- 0.2 degrees C, water. This change was statistically significant for seven minutes at the 95% confidence level (analysis of variance test with Dunnett's multiple range test for significance). There was no significant change in the TMD temperature with any ingestion. The Pearson correlation coefficient for 107 pairs of rectal and TMD temperatures, r = 0.90 (P less than .001), was excellent. It was concluded that hot and cold liquids significantly influence oral temperature measurement for seven to nine minutes following ingestion. TMD temperature is unaffected by liquid ingestion and may allow accurate measurement of body temperature. Further studies are needed to determine the accuracy of TMD temperature over a wide range of body temperature in diverse clinical settings. PMID- 2920077 TI - High-pressure water injection injury to the hand. AB - An 84-year-old man presented with a high-pressure injection injury of the left thumb. The hand-held water gun involved generates less pressure than the grease and paint sprayers usually involved in these injuries. The patient was managed conservatively in the hospital with elevation, observation, and dressing changes. Surgical debridement was not required. This case points out a previously unrecognized hazard of these devices, particularly to older individuals with atrophic skin. PMID- 2920078 TI - Rectal diazepam in pediatric status epilepticus. AB - Status epilepticus is a neurologic emergency with an 8% to 12% mortality. Rapid ablation of seizure activity is imperative. Although intravenous administration of diazepam is the preferred immediate treatment, vascular access is often difficult to achieve. Rectal administration of diazepam is easily accomplished during status epilepticus. Five cases in which diazepam administered in the rectal lumen stopped seizure activity are reported. Rectal diazepam appears to be safe and efficacious. It should be considered as an alternate to intravenous therapy when immediate vascular access is delayed. Rectal diazepam may have great benefit in the prehospital setting. PMID- 2920079 TI - Tracheal obstruction presenting as new-onset wheezing. AB - Two cases of recent-onset dyspnea and wheezing initially treated with bronchodilator therapy for presumed reactive airway disease are presented. Plain film chest radiographs subsequently demonstrated mediastinal masses causing extrinsic tracheal compression. The first patient had inoperable poorly differentiated squamous cell carcinoma resistant to radiotherapy. The second patient underwent resection of a substernal multinodular goiter with complete resolution of symptoms. The physician should always entertain the diagnosis of upper airway obstruction in all adult patients with new-onset wheezing. New-onset adult wheezing of uncertain etiology should prompt the physician to refer the patient for pulmonary function testing with flow-volume loops. PMID- 2920080 TI - Postural guarding and hypertension as initial manifestations of Guillain-Barre syndrome. AB - A child without any prodromal events presented with incapacitating, symmetrical limb pain intensified by any movement. He lacked objective motor weakness or reflex changes. A provisional diagnosis of Guillain-Barre syndrome was not entertained despite sequential examinations that further documented dysesthesia, postural guarding, and hypertension. The clinician must consider Guillain-Barre syndrome as a cause for self-imposed immobilization associated with autonomic dysfunction. PMID- 2920081 TI - Pacemaker electrode perforation of the myocardium: an unusual etiology for recurrent abdominal pain. AB - A 79-year-old man with a permanent pacemaker presented on five separate occasions to the emergency department with recurrent episodes of crampy abdominal pain. Extensive radiographic studies and repetitive labwork were nondiagnostic. Shortly after hospital admission on the fifth visit he experienced cardiac arrest and was successfully resuscitated. Poor pacemaker capture and paced clonic contractions of the diaphragm and abdominal wall were noted, suggesting myocardial perforation by the pacemaker electrode. A new lead and pulse generator were implanted and the patient was discharged without further abdominal discomfort. Implications of pacemaker electrode perforation of the myocardium are discussed. PMID- 2920082 TI - Hemorrhagic compression of the phrenic nerve after streptokinase infusion. AB - A 72-year-old woman with acute myocardial infarction underwent intravenous streptokinase therapy following an unsuccessful attempt at right subclavian vein catheterization. Three hours after initiation of therapy, chest radiograph revealed a markedly elevated right hemidiaphragm. Subsequent computed tomography and fluoroscopy of the chest revealed paralysis of the phrenic nerve by hematoma. This case demonstrates the hazards of attempted cannulation of noncompressible vessels when fibrinolytic therapy is anticipated. PMID- 2920083 TI - The cost of smoking: an emergency department analysis. AB - A representative sample of emergency departments visits was taken to determine the incidence of tobacco-related illnesses. Seven percent of all visits and 12% of gross billings were for illnesses associated with tobacco use. After calculation of attributable risk it was determined that 3% of visits and 5% of gross billings were directly attributable to tobacco. When the latter figures are extrapolated to all emergency departments in the United States, the result is nearly 2.5 million visits and $0.5 billion per year. PMID- 2920084 TI - Detection of colovesical fistula in the emergency department: report of a case. AB - A case of colovesical fistula is described, revealing the pathognomonic findings of terminal pneumaturia and fecaluria. The sensitivity and specificity of various procedures that can be performed in the emergency department for confirmation of the diagnosis are evaluated. Dye studies including methylene blue, the Bourne test, the modified diatrizoate (gastrograffin) test, barium enema and cystography, cystoscopy and colocystoscopic examination, and computed tomography and nuclear medicine scans are discussed as diagnostic modalities. Surgical treatment of colovesical fistula is briefly reviewed. As colovesical fistula are thought to occur in 2% to 22% of patients with known diverticular disease, it is reasonable to question all patients with recurrent urinary tract infection, especially those with known disease of the colon, regarding symptoms of terminal pneumaturia and fecaluria. PMID- 2920085 TI - Massive hemoperitoneum following rupture of hepatic metastases from unsuspected choriocarcinoma. AB - Spontaneous massive hemoperitoneum in a reproductive-aged woman is usually associated with ectopic pregnancy. An unusual cause of intraperitoneal hemorrhage is presented: spontaneous rupture of hepatic metastases from unsuspected choriocarcinoma in a 29-year-old woman 4 weeks postpartum. Although choriocarcinoma is known to have the potential for subsequent hemorrhage of secondary sites, massive hemoperitoneum due to rupture of hepatic metastases is rare. In this case report, the presentation, prognosis groups, and treatment modalities are presented. PMID- 2920086 TI - Serial serum drug concentrations and prolonged anticholinergic toxicity after benztropine (Cogentin) overdose. AB - A 38-year-old man overdosed on benztropine mesylate (Cogentin; Merck Sharpe & Dohme, West Point, PA) and developed anticholinergic poisoning syndrome, which lasted nine days. Serial serum benztropine concentrations were obtained during his hospitalization. Fluctuating benztropine levels suggested that his lengthy intoxication may have been secondary to prolonged, intermittent absorption rather than from slow plasma clearance. This is believed to be the first report of serial serum benztropine concentrations after overdose. PMID- 2920087 TI - Improving medical communication with facsimile (fax) transmission. AB - Facsimile machines (fax) used intensely in business, send copies of documents from one location to another. The medical potential for fax has not been fully explored. A general background in fax and the potential uses for fax between hospitals and within hospitals are described. Fax permits small hospitals to share the resources of larger hospitals and permits a large hospital to share resources more efficiently among its departments. The cost of a fax unit is small compared with the amount of work and time it can save. Clinics and private physicians may also find fax units cost effective. Fax boards, which provide fax capability to personal computers, are also described. The use of fax could streamline the process of patient transfer, telephone patient consultation, medical records retrieval, ECG interpretation, central information distribution, retrieval of medical literature, inpatient pharmacy orders, etc. PMID- 2920088 TI - The acute presentation of intestinal nonrotation. AB - Intestinal nonrotation has been recognized as a cause of obstruction in neonates and children. However, it can also be the cause of significant abdominal pain in adults. The pain is recurrent and often associated with a feeling of distention. If the diagnosis is entertained, it often can be made from basic clinical information. PMID- 2920089 TI - Hypnosis in the emergency department. AB - Five cases are presented wherein hypnosis was used by the emergency physician either as the primary mode of treatment or as an adjuvant to standard medical care. Common hypnotic phenomena (eg, anesthesia, analgesia), as well as novel effects, are reported. The technique used for trance induction and utilization is briefly outlined, and criteria are set forth for the bedside recognition of hypnotic trance. PMID- 2920090 TI - Head trauma and cervical spine injuries. PMID- 2920091 TI - [Asthma and isocyanates]. AB - 1. After having reviewed all the 22 patients in Belgium who are indemnified for isocyanate occupational asthma, the authors cannot find any significant factor that would permit screening and previous eviction (atopy, smoking habits). Every patient suffers from a non-specific bronchial responsiveness even after the end of exposure. 2. The specific RAST HDI, MDI, TDI, performed on 26 exposed workers suggests an IgE-mediated sensitization, that does not appear to be a reliable diagnostic or prognostic factor of the disease. PMID- 2920092 TI - [Tracheobronchial wheezing of childhood turning into asthma?]. AB - In order to study the allergic, immunological, functional and bronchial hyperreactivity (BHR) differences between wheezy bronchitis and perennial asthma, the author studied 285 children aged 4 to 13, divided in three groups: asthma group (A.g.) 102; wheezy bronchitis (W.b.g.) 103; control group 20. The following tests were done: skin prick test (SPT) with D. pteronyssinus (DP), Total IgE, specific IgE anti-DP (RAST), functional respiratory tests (FRT) with a Jaeger whole body plethysmography, and acetylcholine challenge to test the nonspecific BHR. The results show us that there are a greater number of positive SPT and positive RAST, functional abnormalities and a higher sensitivity to acetylcholine in asthmatic children (A.g.) than in those with wheezy bronchitis (differences between the two groups are statistically significant). (table; see text) The findings indicate that it exists in w.b. children an allergo-immunological mechanism and a bronchial hyperreactivity as we observe in asthma, but in a milder degree. W.b. must be carefully watched over because an important number go on to overt asthma. In conclusion, there is a close link between wheezy bronchitis and asthma in children. Atopic w.b. should be treated as an atopic asthma. PMID- 2920093 TI - Neurovegetative assessment in subjects with a risk for hypertension. AB - Cardiacneurovegatative assessment was studied in 60 subjects divided into three groups consisting of 20 normotensive subjects without familial hypertension, 20 normotensive subjects with familial hypertension, and 20 patients with mild hypertension. Cardiacneurovegetative function was investigated by evaluations of these parameters: systolic, diastolic, and mean blood pressure, heart rate, skin temperature, skin conductance, and muscular contraction. These measurements were taken before and after psychological stress (mathematical, Sacks' incomplete sentences, electrical, auditory) and after physical stress (cold, hand grip, head up tilt, lying, and standing). The results showed a significant difference of the psychophysiologic profiles among the three groups. On the contrary, the cardiovascular variables were not very sensitive or well-discriminating, especially when response amplitude was considered. In conclusion we propose the hypothesis that identification of the psychophysiologic profile in certain individuals may be a better marker for future development of hypertension in subjects with a genetic risk. PMID- 2920094 TI - Clinical use of ambulatory blood pressure monitoring. AB - This paper describes the alerting reaction and blood pressure rise induced in the patient when blood pressure measurement is taken by the doctor, emphasizing that this may be responsible for important errors in estimating the real untreated or treated blood pressure in hypertension. It then examines the advantages offered by ambulatory blood pressure monitoring. It is shown that when performed intra arterially this approach may be useful in the diagnosis of pheochromocytoma. However, its wider use as a means to better discriminate between normotensive and borderline or mild hypertensive subjects should not yet be advocated because information on normalcy of ambulatory blood pressure values is limited. Furthermore, although target organ damage of hypertension correlates more closely with 24-hour or day-time blood pressure mean than with sphygmomanometric values, there is insufficient prospective evidence that ambulatory blood pressure is prognostically superior to cuff blood pressure. Finally, noninvasive ambulatory blood pressure monitoring (ie, the only approach suitable for clinical practice) is not accurate because of the relatively large number of artifactual readings and their limited correspondence to intra-arterial values. PMID- 2920095 TI - Blood pressure recovery curves after submaximal exercise. A predictor of hypertension at ten-year follow-up. AB - The purpose of this study is to examine the usefulness of blood pressure recovery curves after submaximal exercise in apparently normotensive young adults as an early predictor for hypertension. Twenty-six college age males in 1977, with normal blood pressures at rest, were given the Harvard Step Test and postexercise blood pressures were recorded. Criteria were set that differentiated a hypertensive from a normotensive response to exercise. In 1987, these individuals were contacted regarding their blood pressure status. Nine out of ten subjects who demonstrated a hypertensive response to exercise in 1977, now have been given the diagnosis of hypertension. Eleven out of twelve subjects who demonstrated a normotensive response to exercise in 1977, now are still considered to be normotensive. A proposed hypothesis is that during the course of this disease, exercise can unmask hypertension in subjects who have the potential for developing hypertension but currently have a normal resting blood pressure. PMID- 2920096 TI - Dietary calcium alters blood pressure in neonatal spontaneously hypertensive rats. AB - Dietary alterations in young genetically hypertensive rats have been shown to have a substantial impact on subsequent blood pressure (BP) development. In the present study, spontaneously hypertensive rat (SHR) pups fostered at birth to high calcium (2%) SHR dams developed significantly lower mean arterial pressures by 28 days of age than pups fostered to low calcium (0.1%) dams (93.7 v 107.7 mm Hg, P less than .01). To determine whether BP differences were due to milk ingestion or to late lactational solid diet consumption, a second experiment was performed. Pups were fostered at birth to medium calcium (1.0%) dams and weaned at 21 days to one of three calcium diets. Blood pressures were determined at 28 days after birth. Pups weaned to the high diet at 21 days had lower pressures at 28 days than pups weaned to the low diet (94.2 v 108.3, P less than .01), suggesting that the pressure variations in the first experiment were due primarily to solid food consumption by the pups late in the suckling period. This rapid BP alteration suggests that neonatal SHR have an enhanced susceptibility to the pressure effects of dietary calcium. PMID- 2920097 TI - Does chronic hyperinsulinemia cause hypertension? AB - The aim of this study was to determine whether chronic hyperinsulinemia, comparable to that found in obesity-associated hypertension, causes sustained increases in mean arterial pressure (MAP) or potentiates the hypertensive effects of angiotensin II (ANG II). Insulin infusion (0.5 or 1.0 mU/kg/min, IV), with plasma glucose held constant by IV glucose infusion, for seven to 28 days raised plasma insulin by five- to ten-fold, but did not significantly change MAP in dogs with reduced kidney mass that were maintained on high sodium intake. In dogs infused with ANG II to cause mild hypertension, insulin for 28 days did not potentiate the hypertension. Insulin infusion did, however, cause modest sodium retention during the first few days of infusion. These findings suggest that additional factors besides hyperinsulinemia per se are responsible for obesity associated hypertension. PMID- 2920098 TI - Saline infusion causes rapid increase in parathyroid hormone and intracellular calcium levels. AB - Previous data demonstrate that increasing dietary NaCl causes an increase in intracellular calcium, possibly due to elevations in parathyroid hormone (PTH). To ascertain whether NaCl can induce a rise in PTH and thereby raise intracellular calcium, five adult males were infused with normal saline, and plasma was analyzed for intact PTH and erythrocytes for intracellular calcium at 15-minute intervals. Saline infusion caused a significant increase in PTH within 15 minutes and in intracellular calcium within 30 minutes. To further demonstrate that PTH was directly responsible for the increased intracellular calcium, erythrocyte suspensions were incubated with PTH, and the PTH caused significant, sustained elevations in erythrocyte total intracellular calcium. These data indicate that NaCl-induced increases in vascular resistance may result, in part, from PTH-induced increases in intracellular calcium. PMID- 2920099 TI - What can be safely said about predialysis treatment? AB - The modern principles of protein restriction and concomitant treatment in the predialysis period were explained. Our own data of a prospective study show the superiority of a keto acid-substituted diet with regard to the progression of chronic renal failure. The advantage of a keto acid administration was underlined. PMID- 2920100 TI - Psychological aspects of low protein diet therapy. AB - One of the main problems in low protein diet is patient's noncompliance and the risk of both depression and reduced quality of life. A pilot study investigated the life-style and the state of mood before and during low protein diet. The results show a deterioration in the life-style and the state of mood. Conclusions are concentrated on the necessity of a systematic psychological well-founded low protein diet educational program. PMID- 2920101 TI - Engulfment of the Philadelphia strain of Legionella pneumophila within pseudopod coils in human phagocytes. Comparison with other Legionella strains and species. AB - In this paper we report our ultrastructural studies of the early phagocytosis of two different strains of L. pneumophila serogroup (SG) 1 (Philadelphia 1 and Knoxville 1) and of L. micdadei. These bacteria replicate, in vivo as well as in vitro, in eukaryotic cells e.g. in monocytes and macrophages. Whether or not the mode of entry of these organisms in phagocytes contributes to their intracellular survival is presently unknown. Whilst internalization of bacteria of the Philadelphia 1 strain occurred within a pseudopod coil, organisms of the Knoxville 1 strain and L. micdadei were phagocytized in the classical manner, i.e. between pseudopods. No ultrastructural differences were observed between the two strains of L. pneumophila SG 1 whereas L. micdadei appeared as shorter rods with an extracellular layer of relatively low electron density. The phenomenon of coiling phagocytosis was not affected by heat-killing the bacteria or preopsonization with specific antibody. Formation of phagolysosomes was seen when cells of the Knoxville strain and L. micdadei were used but not with the Philadelphia strain. In our experiments, the occurrence of coiling phagocytosis was specific for the Philadelphia 1 strain of L. pneumophila and independent of bacterial virulence. Thus, it seems most unlikely that the coiling phenomenon plays any important role in the resistance of Legionella to the killing abilities of phagocytic cells. PMID- 2920102 TI - Cortical bone cross-sectional osteon size in chronic pulmonary insufficiency and regional ischemic states. AB - Cross sectional osteon diameter (D) and Haversian canal diameter (d) were measured in undecalcified, unstained sections from the mid-diaphysis of femoral bones from 13 patients with long lasting chronic pulmonary insufficiency, 10 patients with unilateral thrombosis of the femoral artery and from sex- and age matched normal controls. The cross sectional osteon radius (R = the distance travelled by osteoclats), the mean wall thickness (MWT = (D-d)/2 = distance travelled by osteoblasts) and the structural unit balance (B = R/MWT) were calculated. No significant differences were found in R, MWT og B between chronic pulmonary insufficiency patients and normal controls. Furthermore, no significant differences were found between thrombotic or non-thrombotic legs or between thrombotic legs and their normal controls. This part of the study does not support the concept that the distance travelled by the osteoclasts (R) depends on local supply of nutrients and/or removal of waste products. However, in all patients and controls R was larger in the inner zone than in the outer zone (p less than 0.01). This could be explained by the anatomy of the arterial supply to cortical bone supporting the above hypothesis. PMID- 2920103 TI - Similar chromosomal evolution in a uterine stromomyosarcoma and in one of two leiomyomas from the same patient. AB - The chromosomes from three uterine tumours found in the same patient, two benign leiomyomas (L22 and L23) and a low-grade stroma cell sarcoma with leiomyomatous differentiation (L24), were studied by banding technique. L23 had an abnormal stemline distinguished by triosomy 12. The sarcoma showed a stemline with the same 7q-marker as L23 plus a marker del (12)(q13-24). A comparison with cytogenetically studied myomas collected from the literature showed (1) that there are at least three different recurrent, primary, gross chromosomal changes, viz. t(12;14)(q14-15;q23-24), t(1;2)(p36;p24) and del(7)(q22-31) and that there exist at least five further types of primary chromosomal deviations. The sarcoma showed aberrations identical or closely related to the recurrent structural deviations in myomas. These observations indicate a similar evolutionary pattern in benign and malignant leiomyomatous tumours. PMID- 2920104 TI - Generation and characterization of monoclonal antibodies against Staphylococcus aureus thermonuclease. AB - Monoclonal antibodies (MAbs) against Staphylococcus aureus thermonuclease (TN) were raised by immunizing BALB/c mice with a commercial TN preparation. Six monoclones were generated producing MAbs specific for S. aureus TN as tested in Western blots and ELISA. They all combined with a 17 kD and a 21 kD protein, respectively, both of which showed DNase activity. All MAbs were of IgG1 isotype with kappa light chain. Competition ELISA showed that five of the MAbs recognized a total of three different binding sites of TN, designated I, II and III, respectively. Only the anti-site II MAbs inhibited the DNase activity. A MAb based sandwich ELISA showed a lower detection limit for TN of approximately 0.5 ng/ml protein. Only S. aureus strains (culture supernatants) showed positive ELISA (31 positive/31 tested), although other tested gram positive cocci produced thermostable nucleases. The MAbs have potentials as reagents for rapid and specific detection of S. aureus. PMID- 2920105 TI - Implantation of colon cancer cells onto renal pelvic mucosa. A case report. AB - We report here on a patient with recurrent sigmoid colon carcinoma. Postmortem examination revealed a fist-sized tumor in the retroperitoneum, invasive to the left ureter obstructing its lumen causing hydronephrosis of the ipsilateral kidney. Histological examination of the kidney showed multiple foci of adenocarcinoma cells on the pelvic surface. Invasion into the underlying tissue was not observed, and there was no tumor in the submucosal tissue of the pelvis or in the parenchyma of the left kidney. Cancer cells on the renal pelvic mucosa showed strong immunoreactivities for CEA and CA 19-9. These findings suggest that the tumor foci in the pelvis are formed by the intraluminal implantation of colon cancer cells detached from the ureteric metastasis. Our case presents the possibility of the implantation of carcinoma cells in the human urinary tract. PMID- 2920106 TI - Qualitative assessment and morphometry in the study of the ileal reservoir after restorative proctocolectomy. AB - Little is known about the long-term effects on the reservoir mucosa in patients with ulcerative colitis and familial polyposis coli who undergo proctocolectomy with subsequent construction of ileal reservoir/pouch and ileoanal anastomosis. In these patients, questions regarding adaptation towards a more colon-like mucosa and/or development of (pre)malignant changes are of particular importance. With the aim of designing a method for reliable evaluation of the mucosa in the ileal pouch, biopsies from 10 patients were studied by semiquantitative assessment and morphometry. The findings were compared with those obtained from normal jejunum, ileum, and colon. The following parameters were found to be important: Villous surface density, quantity of goblet cells, number of mitoses, and the presence/absence of predominantly sulphated mucin+ goblet cells. The number of Paneth cells did not show significant changes. The villous surface density was determined by a cycloid test system applied to vertical sections. Semiquantitative assessment was a sufficiently precise method for the evaluation of the quantity of goblet cells. The counting of sulphated mucin+ goblet cells was not reproducible, instead a simple statement about the presence or absence of these cells was judged to be adequate. The number of mitoses and of Paneth cells were counted directly. During the first year of function the ileal pouch showed signs of adaptation towards a colon-like mucosa: Reduction of villous surface density, increased mitotic activity, and appearance of sulphated mucin+ goblet cells. The number of Paneth cells did not show significant changes. The amount of goblet cells was generally not increased, rather reduced in some patients. PMID- 2920107 TI - 'Patient charges and the use of dental services: some evidence'. PMID- 2920108 TI - Vocational training eligibility. PMID- 2920110 TI - 'Soft lasers--have they a place in dentistry?'. PMID- 2920109 TI - 'Identification in the Manchester air disaster'. PMID- 2920111 TI - Fair pay for hygienists. PMID- 2920112 TI - 'HIV infection: comparing attitudes, knowledge and cross-infection control amongst dentists in San Francisco and Great Britain'. PMID- 2920113 TI - 'A physical and microbial evaluation of the re-use of non-sterile gloves'. PMID- 2920114 TI - 'Dentists causing harm with x-rays'. PMID- 2920115 TI - AIDS and dentistry. PMID- 2920116 TI - Funds for research. PMID- 2920117 TI - Intracranial tumours presenting with facial pain. AB - Facial pain is a common presenting symptom in oral surgery outpatient clinics. Among the large number of patients presenting in this way, a small number of patients will be found to have intracranial tumours. Three such cases are described and recommendations made regarding the selection of facial pain patients for further investigation. PMID- 2920118 TI - Cervicofacial actinomycosis in pregnancy. AB - Two cases of cervicofacial actinomycosis in pregnancy are described and the refractory nature of the condition in pregnancy is discussed. PMID- 2920119 TI - Calcification of the dental papilla. A rare finding. AB - An interesting case is reported, of calcification of the dental papilla. As yet, little is known about this asymptomatic calcification, which constitutes a rare radiographic finding, deforming the root of a vital tooth, generally a lower premolar or canine. PMID- 2920120 TI - Simple summary calculations. AB - Methods of measuring the general magnitude or central tendency of sets of data are described, including the mean, median and mode. Similarly, methods of determining the degree of dispersion of the observations about the mean, including range, variance, and standard deviation are presented, together with worked practical examples of their use and importance. The use of algebraic notation in statistics is described. PMID- 2920121 TI - Oral surgery: the diagnosis. AB - It is because we are experts in our field that patients seek our advice about the varied problems that they have in and around their mouths. In order to be able to give such advice, and to effectively treat the patient, a wide range of knowledge, skills and expertise has to be called upon by the practitioner. Listening to, observing, questioning, examining and performing further tests on the patient are all necessary stages along the pathway leading to a diagnosis. Only then is the practitioner in a position to consider the treatment options and to enter into discussions with the patient as to the best course of action to take. The time spent in this part of patient management is time well spent, and will greatly increase the likelihood of a successful outcome to the treatment. PMID- 2920122 TI - Vocational training. A year of opportunity. AB - Vocational training, a stepping stone or a wasted year? The response speaks for itself. The need was perceived for some sort of cushioning between under-graduate protection and the harsh realities of a working day in general practice. The support for the scheme from dental students was overwhelming. The worried conversations of some final year students, discussing their futures, should change dramatically. The new graduate can now face the challenges of his first steps in the real world with more confidence and security. Yet, argues Simon Lewis, vocational training offers much more than just a stepping-stone. PMID- 2920123 TI - AIDS update. PMID- 2920124 TI - NHS: the challenge of change. PMID- 2920125 TI - Belshazzar's feast. PMID- 2920126 TI - 'Keeping up-to-date with tooth notation'. PMID- 2920127 TI - Oral surgery and orthodontic training. PMID- 2920128 TI - 'Community orthodontic services: a local review'. PMID- 2920129 TI - 'Spare a thought for the resident hospital dental surgeon'. PMID- 2920130 TI - 'The control of cross-infection in dentistry'. PMID- 2920131 TI - Management of the small child with gross caries. PMID- 2920132 TI - 'The hospital service today'. PMID- 2920133 TI - A comparison of ibuprofen and dihydrocodeine in relieving pain following wisdom teeth removal. AB - Although dihydrocodeine (DF118) is widely prescribed by general dental practitioners, there is little evidence that it is successful in controlling post operative dental pain. Ibuprofen is known to be effective in this situation. A single dose, double-blind study was carried out in 148 patients to compare 400 mg ibuprofen with 30 mg dihydrocodeine and placebo for treating moderate to severe pain following the removal of unilateral, impacted mandibular third molar teeth under local anaesthesia. An additional dose of either ibuprofen or dihydrocodeine was available after 2 hours. The post-operative ibuprofen reduced pain and produced more pain relief than dihydrocodeine or placebo. Furthermore, fewer patients receiving ibuprofen took additional analgesic at 2 hours. Patients who received ibuprofen as supplementary medication also experienced less pain and had greater pain relief than those receiving dihydrocodeine as supplementary medication, even when their post-operative treatment had been placebo. More patients reported the medication as having been effective if they took ibuprofen either post-operatively or as supplementary analgesia. Ibuprofen is an appropriate analgesic for treating post-operative dental pain. PMID- 2920134 TI - The prevention of cross-infection. Progress in the West Midlands. AB - A questionnaire was sent to a group of general dental practitioners in the West Midlands, one year after they had participated in a previous survey and a year following publication of the British Dental Association's 'Guide to blood-borne viruses and the control of cross-infection in dentistry'. Results show that awareness of the need to safeguard patients and staff from the risks of cross infection continues to grow and that procedures undertaken to reduce the possibility of cross-infection continue to be improved. PMID- 2920135 TI - Oral surgery: assessment and treatment. AB - In arriving at a diagnosis, a dentist will have employed much skill and expertise, but there can be no doubt that in formulating a treatment plan, in addition to skill and expertise, intuition and wisdom (and sometimes inspiration) are required. Whereas the road to diagnosis is paved with objectivity, the road to treatment is paved with subjectivity and instinct. PMID- 2920136 TI - Probability and sampling. AB - The concept of probability is introduced, and the role of probability distributions in statistical theory is discussed, with particular reference to the Normal distribution and its characteristics. Sampling and sampling variation are described, together with sampling error, the standard error of the mean, and confidence intervals for determining the likely magnitude of a population mean. PMID- 2920137 TI - Mortality in the British rubber industry 1946-85. AB - The mortality experienced by a cohort of 36,691 rubber workers during 1946-85 has been investigated. These workers were all male operatives first employed in any one of the 13 participating factories in 1946-60; all had worked continuously in the industry for a minimum period of one year. Compared with the general population, statistically significant excesses relating to cancer mortality were found for cancer of the pharynx (E = 20.2, O = 30, SMR = 149), oesophagus (E = 87.6, O = 107, SMR = 122), stomach (E = 316.5, O = 359, SMR = 113), lung (E = 1219.2, O = 1592, SMR = 131), and all neoplasms (E = 2965.6, O = 3344, SMR = 113). Statistically significant deficits were found for cancer of the prostate. (E = 128.2, O = 91, SMR = 71), testis (E = 11.0, O = 4, SMR = 36), and Hodgkin's disease (E = 26.9, O = 16, SMR = 59). Involvement of occupational exposures was assessed by the method of regression models and life tables (RMLT). This method was used to compare the duration of employment in the industry, the duration in "dust exposed" jobs, and the duration in "fume and/or solvent exposed" jobs of those dying from causes of interest with those of all matching survivors. Positive associations (approaching formal levels of statistical significance) were found only for cancers of the stomach and the lung. The results of the RMLT analysis are independent of those from the SMR analysis, and the study continues to provide limited evidence of a causal association between the risks of stomach cancer and dust exposures, and the risks of lung cancer and fume or solvent exposures in the rubber industry during the period under study. PMID- 2920138 TI - Smoking, occupational exposure to rubber, and lung cancer. AB - A cohort of 1624 employees (957 men, 667 women) in a rubber factory in Shanghai have been followed up since 1972 and their 12 year mortality experience is presented. The relative risk of lung cancer for smokers was 8.5 for men and 11.4 for women and for rubber workers exposed to curing agents or talc powder 3.2 for men and 4.6 for women. PMID- 2920139 TI - Disability, mortality, and incidence of cancer among Geneva painters and electricians: a historical prospective study. AB - The 1916 painters and the 1948 electricians who resided in the Canton of Geneva at the time of the 1970 census were identified and followed up to 1984. During the study period 121 disability pensions were awarded to painters and 59 to electricians. Age standardised incidence of disability per 1000 man-years at risk was higher among painters than among electricians for all neuropsychiatric causes (1.23/1000 and 0.68/1000, respectively) and for all other causes (5.50/1000 and 3.41/1000, respectively). No case of presenile dementia was diagnosed among painters. There was inadequate evidence to indicate that the higher risk of neuropsychiatric disability for painters might have been due to their occupational exposure to organic solvents. A possible toxic effect of these substances on the central nervous system was confounded with alcoholism which was associated with disability from neuropsychiatric disease in 12 of 20 painters and in only one of 10 electricians. Mortality and incidence of cancer were assessed among both cohorts and compared with the expected figures calculated from Geneva rates. Among painters there was a significant increase in overall mortality (O = 254, E = 218.5), in mortality from all cancers (O = 96, E = 75.4), and in incidence from all cancers (O = 159, E = 132.0). For the specific cancer sites, there was a significant excess risk for lung cancer (mortality: O = 40, E = 23.0), which was possibly related to occupational exposure to asbestos and to zinc chromate, although cigarette smoking was not controlled. The significant excesses of biliary tract cancer and of bladder cancer were in accordance with previous observations among painters from other countries. There was also a significant increase in incidence from testicular cancer (O=5, E=1.6), which has not been reported before. For causes of death other than cancer the excesses for alcoholism (O=5, E=0.8). for liver cirrhosis (O=14, E=8.8), for motor vehicle accidents (O=12, E=5.9), and for cerebrovascular disease when allowing for ten years of latency (O=8, E=4.0), were consistent with a probable increased risk of alcohol abuse. Among electricians overall mortality was similar to that expected (O=137, E=139.0). No significant excess risk was found for all cancers or for any specific cancer site. Because of the small number of expected deaths the statistical power was low for the assessment of a possible risk for leukaemia or for brain tumour. PMID- 2920140 TI - Risk of cancer from the use of tar bitumen in road works. AB - Tar bitumens are increasingly being used as a binder in road works. They consist of a standard product of about 70% bitumen and 25-30% tar. Tar bitumens are classifiable as the pyrolysis products of organic materials and are applied hot. Depending on the temperature used there are emissions of various intensities of polycyclic aromatic hydrocarbons (PAH), some of which are carcinogenic. A total of 250 one hour air samples was taken at breathing height on 20 days at 11 road works sites. The region of road paving operations in the immediate neighbourhood of the finishing machine operator and the screedmen were the chosen sampling points. A total of 19 unsubstituted chromatography/mass spectrometry. These included benzo[b]fluoranthene, benzo[a]pyrene, chrysene, dibenzo[a,h]anthracene, and indeno[1,2,3-cd]pyrene, all of which are carcinogenic. The median concentrations of chrysene and of benzo[b,j + k] fluoranthenes (determined en masse) were 9.3 and 2.8 micrograms/m3 respectively. The median concentrations of benzo[a]pyrene (BaP) and indeno[1,2,3,-cd]pyrene were 0.7 and 0.2 micrograms/m3 respectively. Dibenzo[a,h]anthracene had the lowest median concentration with about 0.03 micrograms/m3. Of the resulting shift means, the BaP concentration was over 1 microgram/m3 in about 50% of the cases, over 2 micrograms/m3 in 35%, and over 5 micrograms/m3 in about 15%. Even when the temperature of the paving mix was only between 120 degrees and 135 degrees C. 4.8% of the concentrations (identical to 3 samples) were greater than 2 micrograms BaP/m3, this value was exceeded in 34.9% of the determinations (identical to 30 samples) when the temperature of the tar bitumen was between 135 degrees and 150 degrees C. The highest concentration measured here was 17.8 micrograms BaP/m3. The recommended maximum paving temperature of the paving mix of 150 degrees C was exceeded in about 23% of all cases. The maximum concentration determined under any condition was 22 microgram/m(3). Thus the employment of tar bitumen as a binding material during road paving operations must be regarded as causing a considerable risk to health. The primary task is to ascertain whether tar bitumen can be replaced as a binder in paving for roads and what safety measures are practicable. PMID- 2920141 TI - Environmental and health studies of farm workers in Swedish swine confinement buildings. AB - The relation between the health of workers and the environment in swine confinement buildings was investigated in a study of 57 workers on 30 swine farms in southern Sweden and 55 matched controls. Swine workers reported significantly higher frequencies of respiratory symptoms, more frequent colds and absence due to chest illness, and a history of pneumonia. The increased frequency of symptoms of respiratory disease was related to the number of years and percent of the day spent working with swine. Symptoms were also associated with respirable dust, total dust, endotoxin in total dust, and number of microbes in the air of the work environment. In a multiple regression analysis of the relation between 16 different environmental parameters to work period shifts of five pulmonary function parameters, endotoxin was found to be significantly related to the FEV1 in a dose dependent way. PMID- 2920142 TI - Carpal tunnel syndrome (CTS) and exposure to vibration, repetitive wrist movements, and heavy manual work: a case-referent study. AB - Possible connections between carpal tunnel syndrome (CTS) and exposure to vibrating handheld tools, repetitive wrist movements, and heavy manual work were examined in a case-referent study. The cases were 38 men operated on for CTS between 1974 and 1980. For each case, two referents were drawn from among other surgical cases (hospital referents) and two further referents from the population register and telephone directory, respectively (population referents). Thirty four of 38 cases (89%) and 143 of 152 referents (94%) were interviewed by telephone. An increased prevalence of obesity, rheumatoid disease, diabetes, or thyroid disease was observed among the cases but most did not suffer from any of these disorders. CTS was significantly correlated with exposure to vibration from handheld tools and to repetitive wrist movements but showed a weaker correlation with work producing a heavy load on the wrist. A cause-effect relation between CTS and exposures to handheld vibrating tools and to work causing repetitive movements of the wrist seems probable. Some differences between hospital and population referents indicate that a case-referent study of this type could be biased by inappropriate selection of referents. PMID- 2920143 TI - Sister chromatid exchange analysis in lymphocytes of workers exposed to hexavalent chromium. AB - To investigate the usefulness of sister chromatid exchange (SCE) analysis in lymphocytes as an indicator for mutagenic effects after in vivo exposure to hexavalent chromium (Cr), SCE frequency was analysed in lymphocytes of 44 Cr platers occupationally exposed to hexavalent Cr and 47 controls. Although urinary Cr analysis confirmed that the Cr platers were exposed to Cr, no effects of the exposure on SCE frequency were found. Smokers, both Cr platers and controls, had a significantly higher SCE frequency than non-smokers. These results suggest that SCE analysis in human lymphocytes is not a good indicator of possible mutagenic effects of exposure to hexavalent Cr. PMID- 2920144 TI - Occupational asthma after exposure to azodicarbonamide: report of four cases. AB - Azodicarbonamide (Chemical Abstract Service Registry No 123.77.3) is an organic low molecular weight agent used for blowing and foaming plastics. Finely ground azodicarbonamide can be a pulmonary and sometimes a cutaneous acute sensitiser. Four cases of work related asthma are reported. PMID- 2920145 TI - Ethical conflict in the practice of occupational medicine. AB - The practice of occupational medicine has been portrayed as being fraught with ethical conflict and yet this problem has received little systematic study. A question and case study survey of a randomly selected cohort of members of the American Occupational Medical Association has been performed to examine the extent and nature of this problem in occupational medicine practice in the United States. The results indicate a strong reliance on traditional medical role models in responding to ethical conflict but with significant underlying tension between more deontological physician-patient approaches and more teleological public health approaches. These results have significant implications for the synthesis of bioethical theories based on a perceived complementarity of ethical reality, as well as suggesting important improvements in future occupational medicine training. PMID- 2920146 TI - Reversible airways obstruction and interstitial pneumonitis due to acetic acid. PMID- 2920147 TI - Pleural mesothelioma in a brake mechanic. PMID- 2920148 TI - Calculating expected numbers of deaths in cohort studies. PMID- 2920149 TI - Long-term follow-up of retinal blood flow in diabetes using the blue light entoptic phenomenon. AB - The blue light entopic phenomenon was used to measure retinal blood flow in 87 diabetics and 10 normal controls in a longitudinal study. The time interval between the initial and final studies was 21-39 months (mean 31.4). The retinal blood flow velocity did not change in the 10 subjects in the control group nor in those nine patients with no retinopathy, all but one of whom remained free of retinal lesions. In the 24 with background retinopathy the flow velocity fell significantly from 0.71 (SD 0.35) mm/s to 0.48 (0.13) mm/s (p less than 0.01). The velocity also decreased in the preproliferative group of 16 patients from 0.62 (0.39) mm/s to 0.41 (0.14) mm/s (p less than 0.05). The retinopathy status changed in 11 of this group. In those with proliferative retinopathy (now treated) and those treated previously there was no change in flow velocity. PMID- 2920150 TI - Mesectodermal leiomyoma of the ciliary body: case report. AB - The clinical, light microscopical, and electron microscopical features of a mesectodermal leiomyoma of the ciliary body are presented. This exceptionally rare and apparently benign tumour is considered to be of neural crest origin. In the case described the tumour cells were seen to contain thin filaments with focal densities and conspicuous numbers of mitochondria, and smooth muscle protein was demonstrated by immunohistochemical means. PMID- 2920151 TI - Levels of zinc in plasma, erythrocytes, and hair, and levels of serum copper in patients with retinitis pigmentosa in Turkey. AB - This study was made on 100 patients with retinitis pigmentosa and 23 of their relatives. Their plasma, erythrocyte, and hair Zn and serum Cu levels were compared with those of a control group of 14 healthy persons. No statistically significant difference in these levels was found between the patients with retinitis pigmentosa and the relatives or controls. PMID- 2920152 TI - Retinal and choroidal vascular occlusion secondary to corticosteroid embolisation. AB - We report a case of visual loss following intranasal injection of triamcinolone acetonide and phenylephrine hydrochloride in a 22-year-old female with chronic sinusitis. Clinical examination and fluorescein angiography revealed vascular occlusions which involved multiple small branches of both the choroidal and retinal circulations. The mechanism of such a complication probably involves inadvertent intra-arterial injection into the anterior or the posterior ethmoidal artery, with retrograde flow into the opthalmic arterial system. Precautions can be taken to avoid such complications. PMID- 2920153 TI - A new synthetic material for the brow suspension procedure. AB - This report describes the use of a new synthetic material, combining polyester with carbon, in nine brow suspension procedures. The mechanical properties of polyester, with the fibrous tissue inducing properties of carbon, combine to produce a scaffolding on which fibrovascular ingrowth is possible. Subsequent fibrosis gives a permanent effect. Early results indicate that the material is tolerated well in the eyelid, but the problem of early slippage remains. PMID- 2920154 TI - Repair of an avulsed upper lid and partially severed lower lid. AB - We present a case in which trauma from a broken glass resulted in complete amputation of the upper lid and severe lacerations to the lower lid but with an intact and functioning globe. The avulsed upper lid was repaired as a composite autograft. The possible management of such an unusual case is discussed. PMID- 2920155 TI - Accuracy of routine intraocular lens power calculation in a district general hospital. AB - To assess the accuracy of routine preoperative biometry we reviewed all cases of extracapsular cataract extraction with posterior chamber implant performed at Queen Alexandra Hospital in 1985. Of 471 eyes included in the survey 67.9% were within 1.0 D of the expected refraction and 90.7% within 2.0 D. Factors influencing accuracy are discussed. The necessity of routine preoperative biometry is emphasised. PMID- 2920156 TI - Epithelial downgrowth: a 30-year clinicopathological review. AB - We performed a retrospective clinicopathological review of 124 patients with epithelial downgrowth seen over a 30-year-period at the Massachusetts Eye and Ear Infirmary. The purpose of this study was to determine predisposing factors in the development of epithelial downgrowth, diagnostic symptoms and signs, and the results of various types of treatments. The incidence of this condition after cataract surgery was 0.12%, decreasing to 0.08% over the latter decade. 82% of postsurgical patients with epithelial downgrowth presented to the ophthalmologist within one year following surgery, commonly complaining of decreasing visual acuity, red eye, and pain. The most common presenting signs of epithelial downgrowth were retrocorneal membrane, which was seen in 45% of patients, glaucoma in 43%, corneal oedema in 21%, and a positive Seidel test in 23%. We found that a variety of conditions predispose to epithelial downgrowth but that no one factor was present in all cases. Damage to the underlying endothelium, corneal stromal vascularisation, and stromal downgrowth appeared to be important events not emphasised in prior studies. The angle was partially or totally closed in 87% of enucleation specimens. Patients treated surgically underwent fewer enucleations than those treated medically or not treated. PMID- 2920157 TI - Rabies: ocular pathology. AB - Ocular pathology in the first European case of human bat-borne rabies is described. The patient was a 30-year-old bat scientist who seven weeks after bat bite developed neurological symptoms and died 23 days later. Rabies virus antigens were detected in brain smears. After extensive virological studies the virus turned out to be a rabies-related virus, closely resembling the Duvenhage virus isolated from bats in South Africa in 1980. By light microscopy focal chronic inflammatory infiltration of the ciliary body and of the choroid was found. PAS-positive exudate was seen in the subretinal and in the outer plexiform layers of the retina, and retinal veins showed endothelial damage and perivascular inflammation. Many of the retinal ganglion cells were destroyed. The presence of rabies-related viral antigen in the retinal ganglion cells was shown by positive cytoplasmic immunofluorescence, though electron microscopy failed to identify definite viral structures in the retina. By immunohistochemistry glial fibrillary acidic protein was observed in the Muller's cells, which are normally negative for this antigen but express it as a reactive change when the retina is damaged. Synaptophysin, a constituent of presynaptic vesicles of normal retinal neurons, was not detected in the retina. PMID- 2920158 TI - Fibrinous iritis due to oxybuprocaine. AB - Following minor surgery performed under topical application of oxybuprocaine (Dorsacaine, Novesin) two patients suffered from fibrinous iritis and moderate corneal swelling. We believe that this represents a toxic reaction caused by an inadvertent entry of this drug into the anterior chamber during the procedure. PMID- 2920159 TI - A survey of surgical rotations for oral & maxillofacial surgery trainees. AB - Seventy oral and maxillofacial surgery departments were sent questionnaires to determine whether they made provision for their medically qualified registrars to undergo 1 year's surgical training in recognition for the Part II FRCS oral and maxillofacial surgery option of the Royal College of Surgeons of Edinburgh. Fifty six (80%) replies were received revealing that 11 (19.6%) departments had existing arrangements for a surgical rotation while 14 (25%) had plans to implement one. These results are further reported. PMID- 2920160 TI - How community pharmacy staff manage a patient with possible oral cancer. AB - Community pharmacy staff were surveyed for the advice they would offer to a patient with a history highly suggestive of oral carcinoma. Less than 10% of 57 pharmacies indicated that a dental or medical opinion should be sought. This study confirms that the knowledge of pharmacy staff about oral disease is as limited as it is about systemic disease and suggests that a dental or medical consultation is necessary for persisting complaints. PMID- 2920161 TI - Long standing trismus as the initial presentation of acute catatonic schizophrenia. AB - A case is reported where long standing trismus was the presenting factor in a case of catatonic schizophrenia. The investigations and treatment are described. PMID- 2920162 TI - The Rosai Dorfman syndrome in a 50-year-old male. AB - A case is presented of a 50-year-old man with Rosai Dorfman Syndrome (Sinus histiocytosis with massive lymphadenopathy) who had facial, cervical and cutaneous involvement. PMID- 2920163 TI - Florid cemento-osseous dysplasia (gigantiform cementoma) in a Caucasian woman. AB - The present study reports a case of an uncomplicated florid cemento-osseous dysplasia in a 39-year-old Caucasian woman. The extensive dysplastic lesions affected all jaw quadrants and both radio-opaque and lytic lesions were demonstrated radiographically. Histopathological studies revealed calcified, partly acellular cementum-like tissue. All clinical, radiographic, biochemical and histological features were suggestive of the diagnosis of florid cemento osseous dysplasia. PMID- 2920164 TI - Aggressive calcifying odontogenic cyst--a possible variant of ameloblastoma. AB - A case of an aggressive calcifying odontogenic cyst of the maxilla is presented. It recurred twice after surgical excision over the course of a year and was subsequently treated by maxillectomy followed by radiotherapy. The current histological criteria for the diagnosis of calcifying odontogenic cyst were satisfied but it is argued that they are drawn too widely. Since the majority of calcifying odontogenic cysts are benign in behaviour the presence of cytological indicators of local destruction and invasiveness alongside the usual features of calcifying odontogenic cysts (presence of dentinoid, epithelial ghost-cell degeneration) should be the over-riding prognostic considerations and should thus be reflected in the diagnostic title. Such tumours are best regarded as variants of ameloblastoma rather than as unusually aggressive forms of calcifying odontogenic cyst and an appropriate name would be 'dentinogenic ghost-cell ameloblastoma'. PMID- 2920165 TI - Elastic cartilage in the incisive canal region: report of a case. AB - A man complained persistently of 'gritty bits' coming into his mount from behind the upper front teeth over a period of 10 years. Elastic cartilage was found within fibrous connective tissue of the incisive papilla region and it is suggested that transepidermal elimination of elastotic material, as happens in perforating dermatoses, was responsible for this patients complaint. PMID- 2920166 TI - Focal dermal hypoplasia syndrome with incomplete transverse facial cleft and tumour of the lips. AB - A case of Goltz's syndrome complicated with both incomplete transverse facial cleft and characteristic tumour of the upper and lower lips is presented. Tumour excision and repair of defect were successfully performed. PMID- 2920167 TI - Localisation of retained roots by fibre-optic transillumination. AB - The rationale for the use of fibre-optic transillumination in the location of residual roots is discussed and the technique is described. PMID- 2920168 TI - The Broadgreen osteotomy splint. AB - A modification is suggested to the standard cast metal cap splint which allows accurate and easier localisation in the operative and post-operative phases. PMID- 2920169 TI - New treatment for Ludwig's angina. PMID- 2920170 TI - Comparison of the structural organization and expression of germinal and somatic rat histone H4 genes. AB - A rat somatic histone H4 gene was isolated by screening a rat genomic library using a cloned cell-cycle-regulated human histone H4 gene as a probe. The somatic histone H4 gene was subcloned and the nucleotide sequence was determined. The structural organization and expression of the somatic histone H4 gene and the rat germinal histone H4t gene were compared. Although the predicted amino-acid sequences of the two histones were identical, 49 out of 102 codons differed. The leader sequence of the germinal histone H4t mRNA was 17 bases compared to 40 bases for the somatic histone H4 mRNA, and the 3' terminal sequence of the germinal histone H4t mRNA was 52 bases compared to 75 bases for the somatic histone H4 mRNA. The germinal histone H4 gene also lacked a consensus purine-rich motif which was present in the 5' noncoding region of the somatic histone H4 gene. Northern blot analyses and S1-nuclease protection analyses revealed that the germinal histone H4t and H1t genes were expressed during spermatogenesis in rat pachytene spermatocytes, and the somatic histone H4 gene was expressed only in nongerminal rat cells and tissues. The histone H4t gene was also expressed in some other rat cell types. The differences in expression of the histone H4t and H1t genes may reflect differences in transcription, differences in turnover rates of the mRNAs, or a combination of these factors. PMID- 2920171 TI - Singlet molecular oxygen causes loss of biological activity in plasmid and bacteriophage DNA and induces single-strand breaks. AB - Damage of plasmid and bacteriophage DNA inflicted by singlet molecular oxygen (1O2) includes loss of the biological activity measured as transforming capacity in E. coli and single-strand break formation. Three different sources of 1O2 were employed: (i) photosensitization with Rose bengal immobilized on a glass plate physically separated from the solution; (ii) thermal decomposition of the water soluble endoperoxide 3,3'-(1,4-naphthylidene) dipropionate (NDPO2); and (iii) microwave discharge. Loss of transforming activity was documented after exposing bacteriophage M13 DNA to 1O2 generated by photosensitization employing immobilized Rose bengal, and with bacteriophage luminal diameter X174 DNA, using the thermodissociable endoperoxide (NDPO2) as a source of 1O2. These findings are in agreement with experiments in which plasmid DNA pBR322 was exposed to a gas stream of 1O2 generated by microwave discharge. The effects of 1O2 quenchers and of 2H2O indicate 1O2 to be the species responsible. Strand-break formation in pBR322 and luminal diameter X174, measured as an increase of the open circular form at the expense of the closed circular supercoiled form, was observed without alkaline treatment after exposing the DNA to 1O2, using either agarose gel electrophoresis or sucrose gradient separation. The effect of quenchers and 2H2O indicate the involvement of 1O2 in DNA damage. We conclude that singlet oxygen can cause loss of biological activity and DNA strand breakage. PMID- 2920172 TI - Studies of interactions of porphyrins with transfer RNA by high-resolution NMR. AB - The interactions of tetra-4N-methylpyridyl porphyrin and its zinc(II), copper(II) and manganese(III) complexes with brewer's yeast type V phenylalanine specific tRNA have been evaluated by high-resolution NMR. Differences in chemical shifts have been noted for three proton resonances in response to the presence of small quantities of the free base and the zinc and copper complexes. The protons giving rise to these signals are located on bases T54 and psi 55, both of which are involved in the primary intraloop and interloop hydrogen bonds that hold the D and T psi C loops together in the tertiary structure. In addition, broadening of specific resonances due to hydrogen bonding protons in the D stem at low ratios of porphyrin to tRNA indicates that the association of porphyrins increases the rate of imino proton exchange. The titration of the tRNA with the manganese(III) complex did not reveal shifts or specific broadening comparable to the other porphyrins at low ratios. The changes induced in the NMR spectrum of tRNA by porphyrins define their site of interaction with the polynucleotide. This site, at the outside of the elbow-bend in the tRNA 'L', is different from the locus of binding in tRNA for other classical DNA intercalators. Furthermore, a new mode of binding may be involved that is neither intercalative nor simply electrostatic. PMID- 2920173 TI - Drug induction of P450IIB1/IIB2 and 5-aminolevulinate synthase mRNAs in rat tissues. AB - Expression of the phenobarbitone-inducible cytochrome P-450 mRNA species (cytochrome P450IIB1/IIB2) has been investigated in tissues of rats following administration of 2-allyl-2-isopropylacetamide or phenobarbitone. Using a cDNA probe complementary to these mRNAs, a 2.1 kb mRNA species was detected in liver and lung of untreated rats and to a lesser extent in kidney. This species was not detected in testis, brain or erythroid spleen. Following drug treatment, this mRNA species was increased in liver and kidney, particularly after administration of 2-allyl-2-isopropylacetamide. Using oligomeric probes specific for cytochrome P-450 IIB1/IIB2 mRNAs it was shown that both mRNAs are present in untreated liver and are induced by drug treatment, while in lung only cytochrome P-450 IIB1 was detected and this was not induced. However, in kidney, neither of these mRNAs could be detected, even after drug treatment. This indicates that either the levels of these mRNAs in kidney are below the limit of detection or that a related mRNA is induced which does not hybridize to the oligomeric probes. This represents the first report of a phenobarbitone-inducible cytochrome P-450 mRNA in rat kidney. The tissue-specific drug induction of cytochrome P-450 mRNAs correlated with an increased level of mRNA for 5-aminolevulinate synthase. This finding is compatible with the proposal that induction of 5-aminolevulinate synthase is dependent upon the lowering of heme levels through increased amounts of cytochrome P-450 apoprotein. PMID- 2920174 TI - DNA fork displacement rate measurements in heated Chinese hamster ovary cells. AB - DNA fork displacement rates (FDR) were measured in Chinese hamster ovary (CHO) cells heated at either 43.5 degrees C or 45.5 degrees C for various times. The inhibition of fork movement rate by heat was both time and temperature dependent, i.e., 10-20 min at 43.5 degrees C or 5 min at 45.5 degrees C was required to decrease the FDR to 20-30% of the control rate of 1 micron/min. Following heating, the reduced FDR was found to be constant for at least 75 min. The observed effects of heat on reduced rates of DNA replicon initiation and chain elongation and the increase in DNA with single-stranded regions could be explained by the heat sensitivity of the FDR. Any of these alterations in the DNA replication process may lead to many opportunities for abnormal DNA and/or protein interactions to occur which ultimately may lead to the observed formation of chromosomal aberrations. PMID- 2920175 TI - Purification of carp growth hormone and cloning of the complementary DNA. AB - The growth hormone (GH) was isolated and purified from common carp (Cyprinus carpio) pituitary glands by salt precipitation and HPLC on reverse-phase C18 columns. The carp GH cDNA was synthesized and cloned in Escherichia coli using EcoRI linkers and pBR322 as vector. The positive clones were selected and sequenced. The full-length carp GH cDNA contains 1187 nucleotide basepairs with an open reading frame coding for the precursor form carp GH of 210 amino-acid residues. The partial amino-acid sequence from the protein completely agrees with that derived from the cDNA, with serine as the first residue in mature carp GH preceded by a 22-residue hydrophobic signal peptide. Comparison of the amino-acid sequence of carp GH with those of various species reveals positional identity at 32.4%, 38.8%, 42.0%, 37.2%, 66%, 55% and 49% with GHs of man, rat, duck, bullfrog, salmon, tuna and yellow tail, respectively. PMID- 2920176 TI - A relationship between retinol and cellular retinol-binding protein concentrations in human squamous cell carcinomas. AB - The retinol and retinyl ester concentrations in human xenografted squamous cell carcinomas, with various concentrations of cellular retinol-binding protein (CRBP), were studied, as well as the in vivo uptake and esterification in these tumours of labelled retinol, presented as a complex with plasma RBP. The mean retinol concentration in the different tumours was in the range 3.7-6.2 nmol/g protein, and the mean CRBP concentration was between 16 and 69 nmol/g protein. There was a statistically significant correlation between the retinol and the CRBP concentrations in the same tumour (P less than 0.001; r = 0.622). Calculation of the maximal extent of retinol-saturation of CRBP showed low values (range: 9-26%). Retinyl palmitate, the predominant retinyl ester, comprised approx. 70% of the retinyl esters in the tumours. There was no correlation between the concentration of CRBP and that of retinyl palmitate. The uptake of [3H]retinol from intravenously injected retinol-RBP complex was similar in the four human squamous cell carcinomas studied, and not related to their CRBP concentration. 20% of the radioactivity in tumour specimens was lipid soluble, as compared to 96% in liver specimens, showing that in the former a higher fraction metabolised to polar compounds. Taken together, our results suggest that in these squamous carcinoma cells, factors other than cellular CRBP content are the major determinants of net cellular uptake and esterification of retinol. The cellular retinol concentration, on the other hand, appears proportional to CRBP content. PMID- 2920177 TI - Intracellular free magnesium and phosphorylated metabolites in hexokinase- and pyruvate kinase-deficient red cells measured using 31P-NMR spectroscopy. AB - The erythrocyte metabolism of two patients with nonspherocytic hemolytic anemia caused by a hexokinase deficiency, and a pyruvate kinase deficiency, respectively, were studied with NMR. The complexing of ATP and 2,3 diphosphoglycerate (2,3-DPG) with Mg2+ and hemoglobin (Hb) was determined using 31P-NMR on oxygenated and deoxygenated cells to investigate the influences of these enzyme defects on intracellular magnesium distribution and on Hb oxygen dissociation. In the pyruvate kinase-deficient red blood cells, the 2,3-DPG concentration was almost twice the normal value and the ATP concentration was near the lower limit of the normal range. In the hexokinase-deficient red cell population, the predominance of young cells masked the deficiency. Therefore, reticulocyte control cells were included in this study. In the oxygenated pyruvate kinase-deficient cells, the fraction of ATP that is complexed to magnesium as well as the free Mg2+ concentration were normal, despite the abnormal concentration of 2,3-DPG. In the deoxygenated cells the free Mg2+ concentration was lower than in normal cells. The fraction of Hb complexed with 2,3-DPG was higher than normal in both oxygenated and deoxygenated pyruvate kinase-deficient cells, in accordance with the high p50 of the oxygen-hemoglobin dissociation curve. In hexokinase-deficient cells, two major abnormalities are found: when the cells were deoxygenated, the concentration of ATP and 2,3-DPG fell. This was not observed for any other sample and could, therefore, be a consequence of the hexokinase deficiency. Despite almost normal levels of magnesium-binding metabolites, the free Mg2+ concentration in oxygenated and deoxygenated cels is much lower than in normal cells. This could be a cell-age related phenomenon, since lower free Mg2+ concentrations were also found in reticulocyte control cells. PMID- 2920178 TI - Renal epithelial cell lines (BSC-1, MDCK, LLC-PK1) express 11 beta-hydroxysteroid dehydrogenase activity. AB - Renal tissue of several species has been shown to express considerable 11 beta hydroxysteroid dehydrogenase (11-HSD, EC 1.1.1.146) activity. However, it is uncertain as to which renal cell types exhibit 11-HSD activity. In the present study, we investigated corticosterone metabolism in BSC-1 cells, a continuous renal epithelial cell line derived from the African green monkey (Cercopithecus aethiops). In incubation experiments using 3H-labelled corticosterone and HPLC, we have demonstrated oxidative 11-HSD activity in intact monolayers of BSC-1 cells as well as in BSC-1 cell homogenates. 11-HSD activity in cell homogenates could be stimulated 7-9-fold by the addition of exogenous NADP+ (1 mM). In contrast, no reductive 11-HSD could be detected either in intact cells or in cell homogenates under various experimental conditions which were designed to favor reductive 11-HSD activity. Pilot experiments were performed in cell homogenates from two other renal epithelial cell lines derived from canine (MDCK) and porcine (LLC-PK1) kidney. They also revealed oxidative but no reductive 11-HSD activity. The data provide evidence for an epithelial localization of renal oxidative 11 HSD activity. PMID- 2920179 TI - 31P-NMR evidence for cytoplasmic acidification and phosphate extrusion in syringomycin-treated cells of Rhodotorula pilimanae. AB - 31P-NMR spectroscopy was used to investigate the effects of the phytotoxin, syringomycin, on phosphate metabolism and intracellular pH changes in the yeast Rhodotorula pilimanae. Syringomycin, at levels between 20 and 60 units per 10(8) cells, caused a cellular efflux of orthophosphate. At 40 and 60 unit per 10(8) cells, the efflux was accompanied by a decrease in polyphosphate and an acidification of the cytoplasm. At low temperatures (5 degrees C) and with 75 units per 10(8) cells, these effects were more rapid and pronounced. The efflux of phosphate was confirmed by chemically assaying extracellular phosphate after syringomycin treatment. PMID- 2920180 TI - The effects of heavy metal cations and sulfhydryl reagents on degranulation from digitonin-permeabilized neutrophils. AB - Digitonin-permeabilized neutrophils were exposed to micromolar levels of a variety of heavy metal cations and sulfhydryl oxidants to gain insight into the potential biochemical mechanisms underlying neutrophil degranulation. The results from this study suggest that the oxidation of intracellular sulfhydryl groups may play a role in neutrophil signal transduction. Evidence to support this conclusion is based on the observation that cupric phenanthroline and Cu2+/cysteine, agents reported to induce disulfide bond formation, evoke significant granule enzyme release when presented to permeabilized neutrophils. The stimulatory actions of these compounds occur in the absence of Ca2+ and are blocked by the sulfhydryl reducing agent, dithiothreitol. In addition, we observed marked potentiation of Ca2+-induced secretion by potentially physiological levels of Ni2+. Although we are unaware of any Ni2+-requiring enzymes in eukaryotic cells that are likely to be pertinent to degranulation, the ability of this divalent metal cation to lower the Ca2+ requirements for granule secretion suggests that it may play an important regulatory role in Ca2+ dependent processes. Finally, we observed significant granule release when permeabilized neutrophils were exposed to the heavy metal cations, Hg2+ and Ag+. The apparent stimulatory actions of these metals were the result of lysis rather than degranulation. Thus, the ability of these metals to lyse intracellular organelles such as lysosomal granules may contribute to their toxicological properties. PMID- 2920181 TI - Effect of alanine on in vitro glucose utilization by rat interscapular brown adipose tissue. AB - The rates of either glucose or alanine incorporation into tissue and oxidation to CO2 were studied in rat interscapular brown adipose tissue in order to evaluate the mutual influence of both substrates on their uptake and utilization. Tissue fragments were incubated in vitro in the presence of 1-10 mM glucose and 0.3-1.5 mM alanine. The highest glucose oxidation rate was obtained with the lowest alanine concentrations tested. This suggests that alanine inhibits glucose utilization by this tissue at concentrations that are within the physiological plasmatic range. Glucose levels had little effect upon alanine oxidation, but glucose had a permissive effect on the utilization of alanine. On the basis of these results, it is postulated that this glucose conservation effect of alanine on brown adipose tissue can help to prevent glucose wastage in postprandrial situations. PMID- 2920182 TI - Glucose, glutamine and ketone body utilisation by resting and concanavalin A activated rat splenic lymphocytes. AB - The utilisation of glucose, glutamine, acetoacetate and D-3-hydroxybutyrate were investigated over 72 h of incubation of rat splenic lymphocytes, with and without concanavalin A. Lymphocytes consumed both ketone bodies; acetoacetate was consumed preferentially. The ketone bodies reduced glucose consumption by 30-50%, but had little effect on lactate production. Glutamine uptake was concentration dependent up to 4 mM, and consumption was increased in the presence of concanavalin. Glutamine stimulated glucose consumption and lactate production in both resting and activated cells. Complete oxidation contributed 65% of glucose derived ATP, but less than 40% of glutamine-derived ATP. Glutamine metabolism makes only a minor contribution to lymphocyte ATP generation. PMID- 2920183 TI - Formation of inositol polyphosphates in cultured human sweat duct cells in response to cholinergic stimulation. AB - Inositol phosphate formation in response to cholinergic stimulation was studied in cultured human sweat duct cells, prelabelled with myo-[2-3H]inositol. Formation of inositol mono-, bis-, tris- and tetrakisphosphates was increased after 15 min stimulation by 30 microM carbachol. Formation of inositol 1,3,4 trisphosphate and inositol tetrakisphosphate was significantly increased within 1 min at carbachol concentrations between 10 microM and 100 microM. No detectable increase in inositol 1,4,5-trisphosphate formation was observed at 15 s or 1 min, but an increase was observed after 15 min at a carbachol concentration of 30-100 microM. The data are consistent with an involvement of inositol polyphosphates in the biphasic response of ion transport, to cholinergic stimulation in these cells (see Pederson, P.S. (1986) 6th Professional Conference "Broken Arrow 1986". Genetic and Eptihelial Dysfunction in Cystic Fibrosis (Riordan, J.R. and Buchwalds, M., eds.), Alan Liss, New York and Pedersen, P.S. (1987) Med. Sci. Res. 15, 769-770) and suggest a different pattern of metabolism from exocrine acinar cells. PMID- 2920184 TI - Common or distinct receptors for gastrin and cholecystokinin in gastric mucosa? AB - The differentiation between gastrin (HG) and cholecystokinin (CCK) receptors in gastric mucosa was examined on isolated parietal (F3) and non-parietal (F1) cells from rabbit fundic mucosa separated by elutriation. Direct binding assays on enriched cell populations were performed using 125I-labeled HG-17, 125I-labeled CCK-8 and 125I-labeled CCK-39 as probes. (1) On F1 cells, the dissociation constants (Kd) for the two labeled CCKs were nearly the same (62 pM for CCK-8 and 74 pM for CCK-39) but the binding capacity for CCK-8 was 2-times higher than for CCK-39. HG-17 also bound to this cell population, but its Kd value as about 2 times higher (110 pM) than that of CCK. The presence of two distinct classes of sites on F1 cells can be suggested from competition studies: one more specific for CCK, which bound CCK-8 and CCK-39 with the same affinity, and another class more specific for gastrin, which bound CCK-8 and HG-17 with the same affinity and CCK-39 with a low affinity. (2) On F3 cells, CCK-8 and HG-17 bound with similar affinities (Kd values 81 pM for CCK-8 and 87 pM for HG-17), but CCK-39 did not specifically bind to this cell population. The presence of a binding site more specific for HG than for CCK on F3 cells was confirmed by competition studies in which CCK-33 competed for binding with labeled HG-17 and labeled CCK-8 with a 50 times lower affinity than the other peptides. PMID- 2920185 TI - cDNA and deduced amino acid sequence for the rat hydrophobic pulmonary surfactant associated protein, SP-B. AB - Pulmonary surfactant prevents collapse of lung alveoli by lowering surface tension at the air/liquid interface. The hydrophobic surfactant associated proteins SP-B and SP-C have been shown to be important in surfactant function and metabolism. A cDNA clone for rat SP-B was isolated and sequenced. Northern analysis showed mRNA for SP-B was present in whole lung and was greatly enriched in alveolar type II cells, but was not present in brain, kidney, spleen or liver. A full length transcript of the rat SP-B cDNA clone consists of 1536 bases and encodes an open reading frame of 376 amino acids. The predicted molecular mass of the primary translation product is 42 kDa and the predicted molecular mass of the mature protein is 8 kDa. Extensive homology exists between the rat sequence for SP-B and those reported for human and canine SP-B. The position of 25 cysteine residues has been extremely well preserved across all three species. An N-linked glycosylation site in the COOH region has been conserved across all three species. A search of the NIH database revealed homology between rat SP-B and the active site for the mouse contrapsin serum proteinase inhibitor. PMID- 2920186 TI - Multiple molecular forms of cytochrome P-450SCC purified from bovine corpus luteum mitochondria. AB - Cytochrome P-450 related to side-chain cleavage of cholesterol (P-450SCC) was isolated from bovine corpus luteum mitochondria in the form of its stable cholesterol complex. The isolation procedure included ammonium sulfate fractionation and chromatography on omega-aminohexyl-Sepharose (AH-Sepharose). Corpus luteum P-450SCC was resolved into one minor (AH-I) and two major (AH-II and AH-III) fractions by the chromatography. Results of re-chromatography suggested the possibility that AH-III Fraction was originally complexed with lipidic material. The two major fractions purified by the re-chromatography (AH IIR and AH-IIIR Fractions) showed essentially a single band on sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis and their absorption spectra were indistinguishable from each other. Both fractions were further resolved into two major and some minor bands of P-450SCC by isoelectric focusing on polyacrylamide gel in the presence of a non-ionic detergent, as detected by protein staining, heme staining and immunoblot analysis with anti-bovine P-450SCC monoclonal antibody. Both AH-IIR and AH-IIIR Fractions were further resolved by high-performance liquid chromatography (HPLC) on SP-TSK gel column into two fractions, SP-I and SP-II. These fractions had the same N-terminal amino acid sequence, showed similar catalytic activity and resolved into one major and a few minor bands on isoelectric focusing on polyacrylamide gel. Much more heterogeneity was observed in purified P-450SCC preparations from bovine adrenal cortex mitochondria. These results indicated the presence of multiple molecular forms of corpus luteum P-450SCC as well as adrenal cortex P-450SCC. Computer simulation studies were carried out in order to analyze the mechanism of formation of multiple bands on isoelectric focusing. The multiple bands of corpus luteum P-450SCC could be explained by postulating the presence of two isozymes (or molecular forms) having a pair of sites each with or without a charged group. PMID- 2920187 TI - On the structure of alpha-crystallin: construction of hybrid molecules and homopolymers. AB - The alpha A2 and alpha B2 subunits of bovine alpha-crystallin were purified by chromatofocussing in urea and assembled into homopolymers. Light-scattering measurements indicated their molecular masses were 360 and 420 kDa. The alpha A2 and alpha B2 polypeptides were also used to construct a series of hybrid molecules with alpha A/alpha B ratios ranging from 7:1 to 1:7. Sedimentation velocity analyses, isoelectric focussing under non-deaggregating conditions, circular dichroism spectroscopy and immunochemical analysis indicated that all of the subunits had copolymerized to alpha-crystallin-like aggregates with complete regeneration of the native structure. The polymers could be distinguished on the basis of their differing affinities for the antiserum. This was directly related to the proportion of alpha A2 subunits in each polymer. It was concluded that the alpha A2 and alpha B2 subunits are structurally equivalent and occupy equivalent site in the alpha-crystallin aggregates. It was also concluded that a micellar like quaternary structure was consistent with most previous observations on the protein. PMID- 2920188 TI - Voluntary movement dysfunction in schizophrenics. AB - Several aspects of fine motor control were compared in schizophrenics and two control populations. The motor behavior analyzed was a button-press response in a forced choice paradigm. Three areas of abnormality were seen in schizophrenics: first, the interval preceding the motor response was characterized by reduced motor steadiness prior to the button-press response; second, the motor response was made with excessive force (hyperdynamia); and third, the agonist-antagonist synchrony (motor reversal) was impaired. Schizophrenics on and off neuroleptics did not differ on any measure of motor control, but schizophrenics with clinically observed tardive dyskinesia were found to have significantly less steadiness prior to the motor response than other schizophrenics. PMID- 2920189 TI - Reaction time impairment in schizophrenia and affective illness: the role of attention. AB - A young but chronic group of schizophrenic and affective disorders patients was tested for simple reaction time (RT) and RT while engaged in a concurrent task. The affective disorders patients were subdivided by the presence of psychotic features. The results show that extreme slowing of RT is due to psychoticism and is not characteristic of nonpsychotic affective illness. Extreme intrasubject variability, however, was specific to schizophrenia, and may be a trait marker of the disorder. PMID- 2920190 TI - Sensory gating in schizophrenics and normal controls: effects of changing stimulation interval. AB - Auditory evoked potentials were recorded using a paired click, conditioning testing paradigm in 10 schizophrenics and in 10 normal subjects with no family history of psychotic disorder. The paradigm is used to demonstrate central nervous system gating of responsiveness to auditory stimuli by examining the extent to which the response to the conditioning stimulus diminishes the response to a test stimulus occurring a short time later. Recordings were made at conditioning-testing intervals of 500 msec, 150 msec, and 75 msec to determine subjects' gating of responsiveness to stimuli repeated at various intervals. The schizophrenics had conditioning-testing ratios indicative of poor gating of the auditory P50 wave at the 500-msec and 150-msec intervals, but most patients had good sensory gating at the 75-msec interval. Normal subjects showed good sensory gating at all three intervals. Results suggest that although sensory gating mechanisms responsible for changes in neuronal response at longer intervals are chronically defective in schizophrenics, other gating mechanisms functioning at shorter intervals appear to be intact and function well in most patients. The results may lead to increased specification of the neurobiological basis of sensory abnormalities in schizophrenia. PMID- 2920191 TI - Essential fatty acids in plasma phospholipids in schizophrenics. AB - Blood samples were taken from schizophrenics and control patients in three different centers. The phospholipids were extracted from plasma and their fatty acid composition analyzed. Similar and consistent differences between schizophrenics and controls were observed at all three centers. The n-6 essential fatty acid levels were significantly reduced, whereas n-3 essential fatty acids were elevated. PMID- 2920192 TI - Treatment outcome, seizure duration, and the neurophysin response to ECT. AB - Serum concentrations of immunoreactive neurophysin (IRN) and vasopressin associated neurophysin (hNpI) were measured before and after the first treatment in a course of electroencephalographically monitored electroconvulsive therapy (ECT) given to 19 depressed patients. The difference (DIFF) between the serum concentrations of IRN and hNpI is equivalent to the concentration of oxytocin associated neurophysin. Before ECT the six patients who had a good outcome at 2 months after the course of ECT had a mean serum IRN concentration one-half (p less than 0.05) and a mean serum DIFF concentration one-third (p less than 0.05) that of the 13 patients who had a poor outcome. The increase in serum DIFF concentration (but not IRN or hNpI) after the first ECT correlated with the improvement on the Hamilton Rating Scale for Depression (r = -0.73, p less than 0.005) and the Montgomery and Asberg Depression Rating Scale (r = -0.49, p less than 0.05). The peak percentage increase in serum DIFF concentrations after ECT was 4 times greater (p less than 0.001) in the good outcome group than in the poor outcome group. None of the neurophysin responses to ECT correlated with electroencephalogram-measured seizure duration. PMID- 2920193 TI - Auditory event-related potentials in adolescents at risk for drug abuse. AB - We evaluated sensory and cognitive information processing in noninstitutionalized delinquent male adolescents and in age-matched low delinquency controls. Detailed psychometric testing documented the nature of the aggressive behavior of these young men. Deficits in information processing, as assessed by event-related potential (ERP) techniques, were observed at several levels of the auditory system in the delinquent group. The delinquent group showed delays in wave V of the brainstem auditory evoked potential, shorter N100 latency, and decreased slow wave amplitude of cognitive event-related potentials when subjects were asked to perform a mental task in a noisy environment. It remains to be determined whether or not such information-processing deficiencies are common among delinquent populations and how they might influence the development of delinquent behavior and drug abuse. PMID- 2920194 TI - Measuring cholinergic sensitivity: I. Arecoline effects in bipolar patients. AB - In a previous study, bipolar patients were found to be more sensitive than controls to induction of rapid eye movement (REM) sleep by the direct muscarinic agonist arecoline. We have replicated this observation in a new group of patients and controls. However, much overlap between groups was seen. Muscarinic supersensitivity appears to be present in some bipolar affective patients, but the REM induction procedure may not be the optimal method for measuring it. PMID- 2920195 TI - Measuring cholinergic sensitivity: II. Arecoline effects on metabolic activity in pontine regions of rat brain. AB - Brain imaging studies may help to localize areas particularly sensitive to cholinergic agonists. A study in rats using the 2-deoxyglucose method for studying changes in brain metabolic activity was performed. Among regions in the pons/medulla, arecoline, 0.05 mg/kg ip, increased glucose utilization in the dorsal raphe, median raphe, and basilar pontine nuclei without producing behavioral or cardiovascular effects. These brain areas, along with the hippocampus, may be pertinent to studies of muscarinic supersensitivity in humans. PMID- 2920196 TI - Auditory hallucinations in schizophrenia: does humming help? PMID- 2920197 TI - Serum homovanillic acid concentrations in carbamazepine-treated chronic schizophrenics. PMID- 2920198 TI - Interrater reliability of MECTA SR-1 seizure duration. PMID- 2920199 TI - Menstruation and cerebral blood flow. PMID- 2920200 TI - Dextroamphetamine and dexamethasone suppression test prediction of desipramine response. PMID- 2920201 TI - Sleep EEG in bulimic, depressed, and normal subjects. PMID- 2920202 TI - [Ultrasound hemolysis]. AB - An ultrasound unit for hemolysis for an analytic device is presented which permits hemolysis without the need of a specific insonification chamber which is an unwanted discontinuity along the probe path. This is possible by direct insonification of a flexible tube which contains the flowing blood. The influence of ultrasound power, insonification time and coupling conditions on the result of hemolysis is investigated. PMID- 2920203 TI - [Cybernetic studies of the behavior of human equilibrium using frequency analysis (2)]. AB - The present paper describes the evaluation of static and dynamic experiments investigating the regulation of human balance. The results from a neurologically unremarkable group of test subjects are reported and discussed. These results are compared with those of a patient suffering from multi-infarction disease. PMID- 2920204 TI - Cytogenetic and molecular analysis in Philadelphia negative CML. AB - We studied the clinical, hematologic, cytogenetic and molecular biologic features in four patients with Philadelphia (Ph) negative chronic myeloid leukemia (CML). In all four cases the clinical and hematologic characteristics were indistinguishable from Ph positive CML. Cytogenetic analysis showed a normal karyotype in two patients and chromosomal translocations apparently not affecting chromosome 22 in the other two cases. Southern blot analysis using probes of the bcr region, demonstrated a bcr break-point in all four patients. In situ hybridization with bcr, c-abl, and c-sis probes showed unusual hybridization sites for 5'-bcr and c-abl indicating complex chromosomal rearrangements affecting three different chromosomes in the four patients investigated. Using polymerase chain reaction (PCR) followed by hybridization to oligonucleotide probes specific for the bcr-abl fusion region, the expression of a chimeric bcr abl mRNA was detected. In these patients we demonstrated that (a) CML with a breakpoint in the bcr region without cytogenetically detectable Ph chromosome is characterized by the same genomic recombination of 5'-bcr and c-abl as CML with standard Ph translocation and (b) unusual localization of 5'-bcr and c-abl sequences caused by complex Ph translocation does not interfere with transcription of the bcr-abl fusion gene. PMID- 2920205 TI - The enhancer-like sequence 3' to the A gamma gene is polymorphic in human populations. AB - Cloning and sequencing of the enhancer 3' of the A gamma globin gene of a particularly low G gamma and HbF sickle cell anemia (SCA) patient unexpectedly revealed three base changes (T----C, C----A, and A----G at sites +2285, +2460, and +2676) previously associated with the Seattle-type HPFH, thus leading the authors to suspect that the three mutations were polymorphic. The determination of the incidence of the mutations among various ethnic groups allowed the authors to conclude that this is a widely spread polymorphism, thus excluding any role of these base changes in the determination of the hereditary persistence of fetal hemoglobin (HPFH) phenotype. The origin of these three mutations is not clear because they appear linked, and the same bases (C, A, G) are found in homologous position in the 3' of the normal G gamma gene. As C, A, G at positions +2285, +2460, and +2676 are found with a 100% frequency in African SS patients and presumably among normal Africans (to explain the extremely high frequency among normal American blacks), it is likely that this was the sequence preceding the division of races. The presence of T, C, and A at the same positions apparently occurred after the divergence between blacks and the other races, that is, within the last 1 million years. PMID- 2920206 TI - Graft-v-host disease is associated with autoimmune-like thrombocytopenia. AB - Persistent thrombocytopenia after allogeneic marrow transplantation is associated with poor patient survival. To identify the mechanisms of the thrombocytopenia, we studied platelet and fibrinogen kinetics and antiplatelet antibodies in 20 patients between 60 and 649 days (median 90) after transplantation. Seventeen patients had isolated thrombocytopenia (less than 100 X 10(9) platelets/L): the marrow cellularity was normal in five patients and slightly reduced in 12, and there was no discrepancy between thrombopoiesis and myeloerythropoiesis. Three patients had pancytopenia following marrow graft rejection (two) and relapse of leukemia (one). Only three patients had evidence of increased platelet production, indicating that in most cases there is a poor marrow response to thrombocytopenia early after marrow grafting. There was no correlation between platelet count and splenic pooling, suggesting that hypersplenism was an unlikely mechanism of the thrombocytopenia. Although there was a direct relationship between platelet count and platelet survival, the reduction in platelet survival was greater than what could be explained by the fixed platelet removal found in thrombocytopenic patients; this suggests increased platelet destruction. Seven patients had intercurrent infections that reduced both platelet and fibrinogen survivals. In addition, platelet antibodies bound to autologous or marrow donor platelets were present in five of the 12 patients studied. Patients with antiplatelet antibodies had lower platelet counts (30 +/- 10 X 10(9)/L v. 49.1 +/ 28.7 X 10(9)/L, P less than 0.05) and platelet survivals (1.32 +/- 0.92 days v. 3.58 +/- 2.02 days, P less than 0.05) than patients without antiplatelet antibodies. Furthermore, platelet-bound autoantibodies were present in five of six patients with grade II-IV acute or chronic graft-versus-host disease (GVHD), but were not present in six patients free of GVHD (P less than 0.01). We conclude that persistent thrombocytopenia after marrow transplantation is most often secondary to increased platelet destruction mediated by multiple mechanisms and that platelet autoantibodies are found in patients with acute or chronic GVHD. PMID- 2920207 TI - Elimination of clonogenic tumor cells from HL-60, Daudi, and U-937 cell lines by laser photoradiation therapy: implications for autologous bone marrow purging. AB - Laser photoradiation therapy was tested in an in vitro model for its efficacy in the elimination of non-Hodgkin's lymphoma cells. Results show that at 31.2 J/cm2 of laser light in the presence of 20 micrograms/mL of merocyanine 540 (MC540) there was greater than 5 log reduction in Burkitt's lymphoma (Daudi) cells. Similar tumor cell kill was obtained for leukemia (HL-60) cells at a laser light dose of 93.6 J/cm2. However, to obtain the same efficiency of killing for histiocytic lymphoma (U-937) cells, a higher dose of MC540 (25 micrograms/mL) was required. Clonogenic tumor stem cell colony formation was reduced by greater than 5 logs after laser photoradiation therapy. Under identical conditions for each cell line the percent survival for granulocyte-macrophage colony-forming units (CFU-GM, 45.9%, 40%, 17.5%), granulocyte/erythroid/macrophage/megakaryocyte (GEMM, 40.1%, 20.1%, 11.5%), colony-forming units (CFU-C, 16.2%, 9.1%, 1.8%), and erythroid burst-forming units (BFU-E, 33.4%, 17.8%, 3.9%) was significantly higher than the tumor cells. Mixing of gamma ray-irradiated normal marrow cells with tumor cells (1:1 and 10:1 ratio) did not interfere with the elimination of tumor cells. The effect of highly purified recombinant interferon alpha (rIFN) on laser photoradiation therapy of tumor cells was also investigated. In the presence of rIFN (30 to 3,000 U/mL), the viability of leukemic cells was observed to increase from 0% to 1.5% with a concurrent decrease in membrane polarization, suggesting an increase in fluidity of cell membrane in response to rIFN. However, at higher doses of rIFN (6,000 to 12,000 U/mL) this phenomenon was not observed. The viability of lymphoma cells remained unaffected at all doses of rIFN tested. These results may have therapeutic relevance in patients undergoing interferon treatment who require bone marrow transplantation, as the complete elimination of tumor cells by marrow-purging procedures may be hampered by this increased survival in the presence of interferon. PMID- 2920208 TI - In utero gene transfer and expression: a sheep transplantation model. AB - Retroviral-mediated gene transfer was used to insert a Neo R gene into fetal sheep hematopoietic cells obtained by exchange transfusion from lambs in utero. After gene transfer the cells were returned to the donor fetus. The lambs were examined after birth for the presence of a functioning Neo R gene. Of ten analyzable animals, six were positive for G418 resistant progenitor cells (CFU Mix, CFU-C, BFU-E, CFU-E). Two animals were studied for extended periods of time: 8 and 24 months. Each has demonstrated a pattern wherein positive periods are interspersed with times when there were no detectable G418-resistant cells. We conclude that retroviral-mediated gene transfer can be used to insert genes into early progenitor cells of fetal sheep in utero and that the animals can continue to demonstrate blood cells expressing the gene for more than 2 years after birth. This is a US government work. There are no restrictions on its use. PMID- 2920209 TI - Erythrocyte deformation under shear flow. PMID- 2920210 TI - High-level secretion of tumor necrosis factor-alpha contributes to hematopoietic failure in hairy cell leukemia. AB - Hairy cell leukemia (HCL) is frequently associated with severe pancytopenia. The authors detected high levels of tumor necrosis factor (TNF)-alpha in the bone marrow serum of patients with HCL and found anti-TNF-alpha neutralizing monoclonal antibodies (MoAbs) to be able to enhance hematopoiesis of HCL patients in in vitro colony assays. As potent producers of TNF-alpha, hairy cells could be identified, thus implicating the malignant population in the pathogenesis of hematopoietic failure due to inappropriate secretion of this cytokine. PMID- 2920211 TI - A point mutation in the coding region of uroporphyrinogen decarboxylase associated with familial porphyria cutanea tarda. AB - Familial porphyria cutanea tarda (PCT) is inherited as an autosomal dominant trait caused by decreased activity of uroporphyrinogen decarboxylase (URO-D). In most families with PCT, URO-D mRNA levels are normal but both catalytic activity and immunologic reactivity of URO-D are half normal. We have cloned and sequenced 8 URO-D cDNA transcripts derived from a pedigree member with familial PCT. Three of the cDNAs had sequences encoding normal URO-D but five cDNA's contained a point mutation resulting in a gly----val substitution at amino acid position 281. An oligonucleotide probe complementary to the mutant sequence hybridized to DNA from affected individuals within the pedigree, but not to DNA from normal individuals. Measurements of pulse labeled URO-D in Epstein-Barr virus transformed lymphocytes indicated that the mutant protein has a half-life in vivo of less than four hours. In vitro measurements utilizing labeled URO-Ds generated in a reticulocyte lysate system revealed a 12-hour half-life for the mutant protein compared with a 102-hour half-life for normal URO-D. This is the first URO-D mutation to be characterized in a pedigree with familial PCT. This mutation was not detected in affected individuals from seven other PCT pedigrees, suggesting that PCT can result from different mutations. PMID- 2920212 TI - Inhibition against CFU-C and CFU-E colony formation by soluble factor(s) derived from hairy cells. AB - The inhibitory effect by hairy cell conditioned medium (HCCM) on the growth of granulocyte and erythrocyte colony forming cells was studied in vitro. The percent inhibition of CFU-C formation by HCCM from four hairy cell leukemia (HCL) patients ranged from 36% to 76%, while no inhibition was observed with conditioned medium (CM) obtained from three B-cell chronic lymphocytic leukemia (B-CLL) patients nor from two normal controls. HCCM inhibited specially the growth of rG-CSF responding stem cells. The hairy cell-derived colony inhibitory factor from HCCM was nondialyzable, fairly stable to heat treatment, and trypsin sensitive. Its maximal inhibitory activity against granulopoiesis was observed in the fractions of 5,000 to 6,000 daltons. Moreover HCCM inhibited CFU-E colony formation but not BFU-E. These results indicate that hairy cells produce a factor that inhibits granulopoiesis and erythropoiesis in vitro. This factor may play a role in neutropenia and anemia observed in HCL. PMID- 2920213 TI - Beta-thalassemia due to two novel nucleotide substitutions in consensus acceptor splice sequences of the beta-globin gene. AB - We have identified two novel RNA-splicing mutations affecting a critical nucleotide (nt) in the acceptor consensus sequences at both the IVS-1/exon 2 and IVS-2/exon 3 junctions of the human beta-globin gene. Both mutations are single nt substitutions, T to G and C to A, at position -3 adjacent to the invariant AG dinucleotide. For the IVS-2/exon 3 mutation abnormal splicing into the cryptic splice site at IVS-2 nt 579 is documented. Identification of these two mutations provides further support for the importance of the location of specific nucleotides within the consensus sequences in splice site selection and RNA processing. PMID- 2920214 TI - Molecular characterization of a high A2 beta thalassemia by direct sequencing of single strand enriched amplified genomic DNA. AB - Two families, one of Anglo-Saxon-Dutch descent, and the other, West Indian black, have an atypical beta thalassemia characterized by an unusually high level of Hb A2 in the heterozygous state. Restriction endonuclease mapping showed a deletion of about 1.35 kilobase (kb) in the 5' region of the beta globin gene. Direct sequencing of a specific region of genomic DNA amplified by a new modification of the polymerase chain reaction defined the deletion to be 1,393 base pairs (bp) and to be the same in both families. The deletion extends from 485 bp 5' to the mRNA CAP site to the middle of the second intervening sequence. This deletion, together with three others previously described that remove the 5' end of the beta gene but leave the delta gene intact, are all associated with unusually high levels of Hb A2 in the heterozygous state. PMID- 2920215 TI - Characterization of the potentiation effect of activin on human erythroid colony formation in vitro. AB - Activin, also named FSH-releasing protein, was previously shown to induce hemoglobin accumulation in K562 cells and potentiate the proliferation and differentiation of CFU-E in human bone marrow cultures. Present studies indicate that the potentiation effect of activin is lineage specific. In addition to CFU E, activin caused an increase in the colony formation of BFU-E from either bone marrow or peripheral blood. It had little effect on the colony formation of CFU GM and the mixed colonies from CFU-GEMM. In serum-depleted culture, the effect of activin was shown to be dose-dependent with doses effective at picomolar concentrations. The potentiation effect of activin was exerted indirectly through mediation of both monocytes and T lymphocytes. Activin was also found to increase specifically the proportion of DNA-synthesizing erythroid progenitors from both bone marrow and peripheral blood. It had little effect on DNA synthesis in CFU-GM and in mitogen-stimulated lymphocytes. Addition of the monocytes or T lymphocytes to their respective depleted subpopulations of mononuclear cells reconstituted the enhancing effect of activin on the colony formation and DNA synthesis of erythroid progenitors. These results strongly suggest a specific role of activin in potentiating the proliferation and differentiation of erythroid progenitors in vitro. PMID- 2920216 TI - Evidence for the presence of tissue factor activity on subendothelium. AB - By a variety of methods, tissue factor activity was demonstrated in the subendothelium of rabbit aorta and human umbilical artery. In one method, everted segments of de-endothelialized vessels were mounted in an annular perfusion chamber and the subendothelial surface was exposed to nonanticoagulated human blood under controlled flow. Procoagulant activity was assessed by measuring fibrin deposition on subendothelium and fibrinopeptide A (FPA) levels in post chamber blood. Both fibrin deposition and FPA were decreased with rabbit vessel segments exposed (at a shear rate of 650 seconds-1) to blood from patients with factor VII deficiency and with umbilical artery segments (at shear rates of 90 to 180 seconds-1) that had been pretreated with a monoclonal antibody to human tissue factor. In a second method, everted umbilical artery segments were mounted on a stir bar and the subendothelial surface was exposed, with stirring, to plasma or purified coagulation factors. The capacity of the surface to clot plasma on addition of calcium was inhibited by the antibody to tissue factor. The surface also activated purified 3H-factor X in the presence of factor VIIa, but not in its absence, and this surface property was almost entirely eliminated by pretreating the vessel segments with antitissue factor. Tissue factor activity in subendothelium could play a role in both the arrest of bleeding and in promoting the formation of thrombi at sites of vascular injury. PMID- 2920217 TI - Acute immune hemolysis induced by a degradation product of amphotericin B. AB - We report here on an eight-year-old boy who first developed acute intravascular hemolysis following therapy with amphotericin B (AmB) and subsequently a delayed hemolytic transfusion reaction due to alloantibodies. Although there is as yet no evidence for metabolism of AmB in vivo, the hemolysis appeared to be the result of sensitization against a degradation product of the drug. The patient's serum contained a hemagglutinating IgM antibody that reacted with all red blood cells (RBC) tested in the presence of plasma obtained from patients receiving AmB (ex vivo antigen), but not in the presence of their urine, AmB itself, or with AmB pretreated RBC. These findings indicate that the antibody was directed against a degradation product of AmB, presumably a trace metabolite, that has not yet been identified. PMID- 2920218 TI - Expression of nonspecific cross-reacting antigen species in myeloid leukemic patients and healthy subjects. AB - The reactivity of two monoclonal antibodies recognizing NCA-95 and NCA-55 (MAb 47 and MAb 192, respectively) with a polyclonal anti-NCA serum in myeloid leukemic cells isolated by density gradient centrifugation was compared using an immunofluorescence test (IF). It was observed that the blood myeloid cells in 78.8% of the patients with different types of myelocytic leukemias and all granulocytes of 15 normal donors showed similar expression of the NCA species studied. The leukocytes of the remaining patients did not synthesize the NCA-95 species regardless of the maturation stage of the cells studied. In two patients, synthesis of this NCA form was limited to the fractions containing myelocytes and metamyelocytes. We have found that all anti-NCA antibodies studied recognized different antigenic epitopes in a myeloid cell series. A relationship between the patient's survival and the proportion of NCA-containing cells was also observed. PMID- 2920219 TI - Blood erythroid progenitors (CFU-E and BFU-E) in acute lymphoblastic leukemias. AB - Circulating erythroid progenitors from 14 patients with acute lymphoblastic leukemia (ALL) and from 8 healthy subjects were studied in culture to determine the frequency and size of CFU-E- and BFU-E-derived colonies. Cells were cultured in a plasma clot system, and hemoglobinized colonies identified by diaminobenzidine reaction. The numbers of CFU-E and BFU-E per milliliter of peripheral blood were greatly increased in 10 patients when compared to controls. In 13 patients, the size distribution of BFU-E-derived colonies, analyzed by counting the number of subunits in each colony, was also found to differ significantly from controls, with a large excess of small colonies and a low percentage or a total lack of large colonies. This abnormal BFU-E size distribution was partially corrected, in the 5 patients tested, by the addition to the culture medium of 10% phytohemagglutinin-leukocyte-conditioned medium (PHA LCM). Bone marrow crowding out of the normal progenitors, as well as disturbances in the cellular interactions involved in their normal development, most likely explain these results and these factors could be implicated in the frequent pancytopenia of ALL. PMID- 2920220 TI - Aplastic anaemia. PMID- 2920221 TI - Bioassays for detection of aldicarb in watermelon. PMID- 2920222 TI - Minicolumn technique for the detection of deoxynivalenol in agricultural commodities. PMID- 2920223 TI - Organochlorine insecticide residues in soils used for vegetable and tropical fruit production in the Cudgen-Duranbah area of New South Wales. PMID- 2920224 TI - Spontaneous occurrence of ochratoxin A residues in porcine kidneys in Belgium. PMID- 2920225 TI - Long-term effects of land application of aqueous oil effluent on photosynthetic efficiency of certain varieties of Oryza sativa L. PMID- 2920226 TI - Organochlorine residues in human adipose tissue in Spain: study of an agrarian area. PMID- 2920227 TI - An improperly labeled container with chloropicrin: a farmer's nightmare. PMID- 2920228 TI - Pesticide exposure to a greenhouse drencher. PMID- 2920229 TI - Method for the preliminary assessment of aquatic contamination sites using sediment extract toxicity tests. PMID- 2920230 TI - Lead poisoning of northern pintail ducks feeding in a tidal meadow contaminated with shot from a trap and skeet range. PMID- 2920231 TI - Sodium nitrilotriacetate (NTA) influences the larval development and metamorphosis of marine invertebrates. PMID- 2920232 TI - Cadmium-binding proteins in midgut gland of freshwater crayfish Procambarus clarkii. PMID- 2920233 TI - Effects of organic and inorganic lead on the oxygen equilibrium curves of the fresh water field crab, Barytelphusa guerini. PMID- 2920234 TI - Metabolism of chlorobenzene and hexachlorobenzene by the zebra fish, Brachydanio rerio. PMID- 2920235 TI - Effects of bleached kraft mill effluent (BKME) on the schooling behavior of vendace (Coregonus albula L.). PMID- 2920236 TI - Studies on the role of gastrointestinal tract contents in the methylation of inorganic mercury compounds. PMID- 2920237 TI - Histopathological effects of monosodium methanearsonate (MSMA) on New Zealand white rabbits (Oryctalagus cuniculus). PMID- 2920238 TI - Effect of petroleum vapors inhalation on intestinal absorption of glucose and some amino acids in the rat. PMID- 2920239 TI - Absorption of mercuric chloride and mercuric sulphide and their possible effects on tissue glutathione in mice. PMID- 2920240 TI - Maintained improvement in calcium balance and bone mineral content in patients with osteoporosis treated with the bisphosphonate APD. AB - The effects of the (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD) in osteoporosis were investigated in a series of open studies. Seven patients received a high dose of 600 mg/day of APD orally and showed an increase in calcium balance of 5.5 mmol/day (P less than 0.01) within a period of 10 days. In a group of 14 patients with osteoporosis, receiving a low dose of 150 mg/day of APD continuously, the mean calcium balance rose from -0.72 +/- 0.59 mmol/day before treatment to 1.33 +/- 0.87 mmol/day (P less than 0.005) after 1 year. In 24 patients treated with APD 150 mg/day for a mean period of 3.7 years (range 1.4 6.2) repeated dual photon absorptiometry measurements of the lumbar spine showed a mean rate of increase in bone mineral content of 3.1 +/- 1.0% per year (P less than 0.005). This yearly gain in bone mineral content appeared continuous for several years of treatment. In a comparable group of 19 patients with osteoporosis who also received conventional care and treatment but no APD, no significant changes in bone mineral content were found. Addition of a low dose of APD to conventional treatment of osteoporosis does not only prevent bone loss but induces a continuous gain in bone mass. These results justify long-term prospective studies with uninterrupted low dose APD treatment in osteoporosis. PMID- 2920241 TI - Bone mineral density of the spine and proximal femur in normal and osteoporotic subjects in Japan. AB - Bone mineral density (BMD) of the spine and proximal femur in Japanese men and women was investigated with dual photon absorptiometry, using gadolinium-153. Peak bone mass of the spine (L2-4) was 1.20 g/cm2 in women which was lower than that of men by 4.7%, whereas BMD of the femoral neck was 0.91 g/cm2 in women and lower than in men by 13.3%. Bone loss was faster in postmenopausal women than in men of the corresponding age, and the regressions of BMD on age were 6.7-times higher at L2-4 and 5.1-times higher at the femoral neck than in men. Such rates of loss became slower both in the lumbar spine and proximal femur in women after 70 years of age, but the density at the proximal femur kept decreasing in men after 70 years of age. Fracture thresholds of each region were evaluated at the 90th percentile for BMD of L2-4 in patients with vertebral crush fractures and for BMD of the proximal femur in patients with hip fractures. The fracture threshold was 0.97 g/cm2 at the spine and 0.67 g/cm2 at the femoral neck in women. BMD values at the spine and proximal femur in normal Japanese men and women appear to be lower than those in white American control population. PMID- 2920242 TI - Is there a need for more theoretical biology? PMID- 2920243 TI - Unconscious guilt as a cause of sexualized relationships. AB - The author summarizes 4 years of intensive psychotherapy with a patient who engaged in various forms of self-destructive behavior, including the sexual fondling of his 14-year-old stepdaughter. The author illustrates the important role that unconscious guilt may play in motivating a patient to engage in what ordinarily would be thought of simply as illicit drive-gratifying behavior. She describes the patient's reported childhood traumas and the therapeutic process of treatment, and gives examples of interpretations that facilitated the patient's efforts to gain control over his self-destructive behavior. PMID- 2920244 TI - Crisis intervention through early interpretation of unconscious guilt. AB - The author describes an approach to crisis intervention based on the assumption that a crisis reconfirms a patient's unconscious pathogenic beliefs and increases unconscious guilt. The nature of the psychopathology can be understood in terms of the patient's history, current life problems, and testing of the therapist. Treatment involves offering the patient a dynamic evaluation that includes interpretation of the role of pathogenic beliefs and guilt in the crisis. This approach provides symptomatic relief and may lead to incipient personality change. Improvement may be due in part to the greater openness to change characteristic of persons in crisis. However, this approach seems effective primarily because patients are enabled to disconfirm their pathogenic beliefs and thereby reduce unconscious guilt. PMID- 2920245 TI - Critique of a new view of unconscious guilt. PMID- 2920246 TI - Reality testing and judgment. AB - Both clinical and research efforts will be enhanced when professionals clearly understand the meaning of the terms reality testing and judgment. Until recently, clinicians and writers often failed to differentiate between them and also introduced other similar words and phrases that further diminished the specificity of the term reality testing. After reviewing some recent efforts to clarify the terminology, the author discusses the critical role of sensation as a precursor to perception and cognition, and the interaction of all three elements in the development of reality testing. He concludes with proposals to clarify the clinical applications of the terminology. PMID- 2920247 TI - The role of culture and family in mental illness. AB - A case is presented of a 25-year-old Oriental man who shocked his family by revealing his homosexuality, choosing atheism over his family's traditional Christian religion, and attempting suicide. The discussant examines the cultural implications of the family's reactions to the patient's clinical picture. PMID- 2920248 TI - The role of unconscious guilt in psychopathology and psychotherapy. AB - Using a new psychoanalytic perspective, the author explains how irrational unconscious guilt originates, how it produces psychopathology, and how it is mastered in psychotherapy. According to this perspective, unconscious guilt is a product of repressed irrational beliefs derived from traumatic childhood experiences. The author emphasizes the role of guilt as a source of resistance and transference, and he explains patients' unconscious efforts to master problems with guilt through an ongoing process of testing the therapist. Therapeutic outcome significantly depends on the degree to which therapists pass patients' tests and accurately analyze patients' guilt-based resistances and transferences. The author briefly describes an empirical study based on these concepts. PMID- 2920249 TI - Renal hydatid disease. Importance of pre-operative diagnosis. PMID- 2920250 TI - Primary osteogenic sarcoma of the kidney. PMID- 2920251 TI - Spontaneous regression of subcutaneous and pulmonary metastases from renal carcinoma. PMID- 2920252 TI - Another approach to the treatment of priapism. PMID- 2920253 TI - Ureteric meatotomy guided by antegrade insertion of a double J splint. PMID- 2920254 TI - Irrigation and acute ureteric dilatation--as for ureteroscopy. AB - The effects of irrigation with sterile and infected saline after acute ureteric dilatation by graded Teflon dilators were evaluated renographically and histologically in minipigs. The minipig ureter was dilated from its normal calibre of 4 F to 10 F, and 100 ml of sterile or infected saline were then introduced from a height of 60 cm under gravity. One week after irrigation and dilatation the ipsilateral kidney was either functioning less than 10% or there was an obstructive nephropathy. Histology at 3 months suggested that extravasation of infected irrigating fluid was the most likely cause of ureteric stricture formation. PMID- 2920255 TI - The severity of urinary incontinence in women. Comparison of subjective and objective tests. AB - The subjective assessment of urine loss in 84 incontinent women was quantified by using a 10-cm visual analogue scale. These results were compared with the results of a 2-h pad weighing test. We found no relationship between a patient's subjective impression of the severity of her incontinence and the corresponding objective assessment by a 2-h pad weighing test. PMID- 2920256 TI - Assessment of the results of Stamey bladder neck suspension. AB - A total of 48 patients with genuine stress incontinence underwent endoscopic bladder neck suspension; 36 patients (75%) were completely cured of their incontinence but 12 (25%) suffered recurrent leakage. In 2 cases this was due to infection and erosion of the vaginal sutures; in 4 cases failure was ascribed to a small capacity bladder and "pipe-stem" urethra. In the remaining 6 unsuccessful cases the Stamey sutures had cut through flimsy endopelvic fascia. It was concluded that endoscopic bladder neck suspension has advantages over colposuspension in terms of reduced dissection and hospital stay, but its success rate is lower than originally reported. Failures due to suture infection and buttress displacement may be avoided by not using Dacron and, instead, by picking up vaginal subdermis with nylon sutures--the same tissue used to provide support in a Burch colposuspension. PMID- 2920257 TI - Lack of relationship of conus reflexes to bladder function after spinal cord injury. AB - A series of 20 patients with acute complete suprasacral cord lesions underwent serial urodynamic assessment of vesicourethral function and serial measurement of sacral reflex latency times (SRL) and reflex threshold throughout a follow-up period of 42 to 83 weeks (mean 50). No correlation was found between any pattern of SRL latencies or reflex thresholds and subsequent bladder behaviour. The reproducibility of sacral reflex latencies was found to be poor (mean variation of serial measurements from initial reading 21%) and could not be explained on the basis of "dynamic" neurological recovery. Studies using the bladder as a stimulus site were unreliable. The value of SRL studies in detecting subtle neurophysiological changes is discussed. PMID- 2920258 TI - Bladder replacement by ileocaeco-urethrostomy or ileo-urethrostomy with a reservoir after cystoprostato-vesiculectomy for bladder cancer. A functional evaluation. AB - The purpose of this study was to evaluate the function of the intestinal segments used to replace the bladder after cystoprostato-vesiculectomy. The series included 30 patients, 10 of whom underwent clinical, radiological, urodynamic and electromanometric investigations. Seven patients had an ileocaeco-urethrostomy (ICUS) and 3 had an ileo-urethrostomy with a reservoir (IR). The results were good in all patients and there was no sign of tumour recurrence. All were completely continent during the day but during the night only those who observed the 2-h intervals between voiding were continent. The radiological findings for 1 patient showed grade I asymptomatic vesicoureteric reflux. In all cases, periodic pressure waves were observed during electrocystomanometric tests at basal levels, with the IR patients showing waves higher in frequency and lower in amplitude. Prostigmin induced a significant variation in motor activity in IR patients only. The urodynamic tracings showed an almost physiological flow in both groups. Cystomanometry revealed good compliance in both types of new bladders. The height and width of contraction waves during filling was greater in ICUS than in IR patients. Good perineal sphincteric activity was demonstrated by electromyography. Low passive resistance was indicated by the urethral pressure profile. Preliminary analysis of data indicated good functional micturition and renal function in both ICUS and IR patients. Slight differences were found between the two intestinal segments used for bladder replacement. PMID- 2920259 TI - Three years' experience with an ileal low pressure bladder substitute. AB - At the beginning of this century it was realised that peristalsis would cause incontinence if bowel was used for augmentation or substitution of the bladder. Trans-section of the antimesenteric border and cross-folding of the intestinal segments (Goodwin's cup-patch technique) is an efficient means of solving this problem and has been successfully used in the Kock pouch. We anastomosed the ileal low pressure reservoir to the membranous urethra in 22 male patients following radical cystoprostatectomy for bladder cancer. The mean observation time was 16 months (range 3-36). The capacity of the bladder substitute increased with time, the average being 450 ml after 6 months. In the first 4 patients with a short (2-5 cm) intestinal segment between the pouch and the urethra, micturition was prolonged, residual urine varied from 50 to 300 ml and bacteriuria was found. Occasional expulsions of several ml of urine were caused by peristalsis within this short tubular segment. In the following 18 patients, the low pressure reservoir was anastomosed directly to the membranous urethra. Micturition was good, with no notable residual urine, no bacteriuria and no paroxysmal urinary incontinence. However, a safety pad is used by half of the patients because once or twice a week, mainly at night, a few ml of urine may be lost. No significant changes in serum electrolytes, bicarbonate or creatinine were noted. With the three different antireflux techniques used, no obstructive or inflammatory changes in the upper urinary tracts were found, although no long term antibiotic prophylaxis was given. PMID- 2920260 TI - The Mitrofanoff principle for continent urinary diversion. AB - A continent urinary diversion was formed for 16 patients using the Mitrofanoff principle for continence. As originally described, this system used the appendix tunnelled into the bladder to form a continent catheterisable vesicostomy. We have expanded the technique and have used all available narrow tubes as continent conduits (ureter 10 cases, appendix 5, Fallopian tube 1). The urine container was made of large and small intestine and bladder in several combinations. The system has been very satisfactory: 14 patients were continent and able to catheterise; 1 required a revision to achieve continence and 1 awaits revision; 3 patients required revision procedures for stricture. PMID- 2920261 TI - The enigma of interstitial cystitis--an autoimmune disease? AB - Interstitial cystitis (IC) is characterised by recurrent inflammation and destruction of bladder tissue without obvious cause. To determine whether this self-perpetuating disease is the result of an autoimmune disorder, we studied 26 patients with IC of mean duration 5 years and compared the results with those of a control group of similar age and sex with other urological complaints. We performed a standard autoimmune profile and looked for specific antibodies to normal human bladder in the serum, using an indirect immunofluorescence technique. Deep bladder biopsies were examined by conventional histology and cryostat sections were studied with peroxidase-conjugated anti-human antibodies in a search for immunoglobulin deposition within the bladder. Seventeen of 26 patients with IC (65%) and 5 of 14 controls (36%) demonstrated non-organ-specific antibodies; 40% of those with IC had anti-nuclear antibodies; 18 IC patients (75%) and 4 of 10 controls (40%) had anti-bladder antibodies present in the serum, but 5 healthy volunteers showed no such antibody activity. There was no statistically significant difference between the two groups for either type of antibody (Fisher's exact test). Only 5 of 17 patients with IC (29%) showed immunoglobulin deposition in the bladder epithelium, a similar proportion to controls (38%); 4 of these 5 had circulating anti-bladder antibodies present in the serum. Although IC patients demonstrated a non-specific increase in antibody formation, this was not significantly different from a similar group of other urological patients. The lack of specificity makes this immunological response more likely to be a secondary phenomenon associated with inflammatory damage to the bladder rather than the primary cause of the disease. PMID- 2920262 TI - Concurrent adriamycin and radiotherapy in locally advanced bladder cancer. AB - A prospective 2-phase study was performed on 24 patients with locally advanced transitional cell carcinoma of the urinary bladder to evaluate the toxicity of integrated treatment with Adriamycin 10 mg/m2 (group A) or 20 mg/m2 (group B) and hyperfractionated, accelerated radiotherapy. Local and systemic toxicity with Adriamycin 10 mg/m2 was significantly lower than with 20 mg/m2. Complete tumour remission was achieved in 18 patients (6 of 8 patients in group A and 12 of 16 in group B). In 12 cases the treatment could be stopped after the first series. PMID- 2920264 TI - Urine microscopy and culture in the selection of patients for urinary tract investigation. AB - In a 1-year laboratory-based study the validity of certain findings on microscopy and culture of mid-stream urine specimens as predictive of the presence of structural or functional abnormalities of the urinary tract was tested. During 1986, infection was diagnosed in 12,705 specimens sent to the laboratory by general practitioners; in the light of the findings a comment suggesting the possibility of underlying urinary tract pathology was appended to the reports of specimens from 652 patients. Data were available from the investigation of 233 of these patients. The percentage in whom abnormalities were detected considerably exceeded that reported from studies of bacteriuric children and of adult women with symptoms. It is suggested that the use of these criteria may assist clinicians to select, from the very large number of patients who suffer from urinary tract infection, those who require investigation. PMID- 2920263 TI - New combination chemotherapy programme for bladder cancer. AB - Forty patients with either metastatic, post-radiotherapy recurrent, or poor prognosis locally advanced transitional cell carcinoma of the bladder were treated in a new combination chemotherapy programme with methotrexate, vinblastine, mitozantrone and JM8 (carboplatin); 33 patients were assessable for response. There were 9 complete responses (27%), 12 partial responses (36%) and 7 disease stabilizations (21%); 5 patients (15%) had progressive disease. The median duration of complete response has not been reached and is in excess of 9 months (range 4- greater than 18 months). This regimen was without significant toxicity and this is in contrast with M-VAC, which is thought to be currently the most effective treatment for urothelial cancer. PMID- 2920265 TI - Volatile N-nitrosamines in urinary catheters. AB - Levels of volatile N-nitrosamines were measured in 10 brands of latex and 2 brands of silicone catheters using high performance liquid chromatography. The cytotoxicity of catheters from identical batches was determined by measuring the inhibitory effect of catheter extracts on the uptake of 3H-labelled thymidine into L-929 fibroblasts in culture (IC50). The most frequently encountered nitrosamines were N-nitrosodi-n-butylamine and N-nitrosodiethylamine. Total N nitrosamine levels in excess of 100 ng/g were found in 6 of the 16 catheters tested. When compared with the cytotoxicity of the catheters a significant correlation was found, with increasing nitrosamine content being associated with greater cytotoxicity. In view of the reported toxic and carcinogenic effects of these compounds it is suggested that the nitrosamine content of catheters be routinely monitored and safe regulatory limits be imposed. PMID- 2920266 TI - Oestrogen in the treatment of prostatic carcinoma. What is the safe and effective dose of ethinyloestradiol? AB - The treatment of prostatic carcinoma with diethylstilboestrol (DES) and ethinyloestradiol (Lynoral) has become less popular since the introduction of new forms of treatment such as antiandrogens, estramustine phosphate and LHRH analogues. One of the reasons for this decline in popularity is the risk of cardiovascular side effects during treatment with oestrogens. In the literature, different dosages of DES and ethinyloestradiol are recommended and different rates of cardiovascular side effects are reported. In a prospective study, 18 patients were treated with ethinyloestradiol 0.05 mg/day. In most cases this lowered the plasma testosterone permanently below castrate level during therapy. Also, because the acid phosphatase returned to normal in almost all patients, this treatment seemed adequate. In 4 patients the treatment was stopped because of side effects, in 3 of these because of cardiovascular complications. The cardiovascular side effect at this dose are considerable (29%) but comparable rates are reported in some studies following placebo treatment of patients with prostatic carcinoma. PMID- 2920267 TI - Urethral substitution in women. AB - A series of 30 female patients underwent total urethral substitution for a variety of conditions, usually urogenital sinus abnormalities or post-irradiation vesicourethrovaginal fistulae. Five different techniques were used: bladder flap neourethroplasty, neourethroplasty using a urinary tract remnant, vaginal/urogenital sinus neourethroplasty, pedicled labial skin tube neourethroplasty and colonic substitution neourethroplasty with synchronous implantation of an artificial sphincter. Bladder flap neourethroplasty is appropriate if the bladder size is adequate and if the bladder neck is incompetent, but stress incontinence is a common complication which must be anticipated and dealt with proleptically. Vaginal/UG sinus neourethroplasty is preferred if the bladder neck is competent enough to preserve continence. When no other tissue is available, particularly after radiotherapy, a pedicled labial skin tube neourethroplasty gives the best results. Colonic substitution with the implantation of an artificial sphincter is not satisfactory. Any surgically created neourethra should be wrapped with either labial fat pads or omentum and, in the absence of a competent bladder neck, with an artificial sphincter cuff to support the urethra and to prevent it telescoping, and for use as a back-up if continence is not adequate. PMID- 2920268 TI - Epididymo-orchitis and Brucellosis. AB - A series of 40 patients presented with epididymo-orchitis between January 1983 and August 1985. In 14 brucellosis was diagnosed. In 10 of these (72%) both testis and epididymis were involved and 1 had bilateral disease. All patients with brucella epididymo-orchitis were treated with streptomycin and tetracycline and complete resolution occurred in 8 (57%). PMID- 2920269 TI - Effect of phentolamine on venous return in human erection. AB - A group of 25 patients underwent Doppler penile blood examination and cavernometry before and after 5 mg of phentolamine injected intracavernously. The organic or psychogenic nature of impotence was determined by psychological testing, the intracavernous injection of papaverine, hormonal evaluation, neurological examination, Doppler penile blood flow measurement and cavernometry for vascular investigations. The intracavernous injection of phentolamine had no effect on the venous return and it provoked penile arterial dilatation. The erectile angle, which was also measured, was less evident than after the injection of papaverine. The results confirmed the fact that an increase in arterial inflow alone is not sufficient to induce a rigid erection in man. PMID- 2920270 TI - Early calcification of haematoma in the renal pelvis. PMID- 2920271 TI - Renal parenchymal malakoplakia. PMID- 2920272 TI - The use of milk progesterone analysis to monitor reproductive activity in the camel (Camelus dromedarius). AB - Milk progesterone profiles were used to monitor the ovarian changes during the post-partum period of five she-camels. Milk samples were collected daily for 60 days from four suckling camels (1-4) and from one animal whose calf died on day 3. Progesterone was determined using the Ovucheck Bovine progesterone kits. The first increase of progesterone level in the five animals occurred on days 28, 26, 21, 24 and 20 respectively. At least two progesterone peaks of 6 +/- 2 SD days' duration occurred during the 60 days. An early one day peak was also noticed in three animals. PMID- 2920273 TI - Changes in limb loading with lameness for a number of Friesian cattle. AB - Lameness in cattle is an expensive problem. Gait studies may assist in understanding the factors involved. The gait changes of four lame cows were related to the gaits of non-lame cows. The vertical forces and horizontal fore and-aft forces during the stance phase of steps were investigated using a force plate. The maximum vertical force (MVF) was often reduced on lame limbs. The horizontal forces showed an initial decelerative force followed by an accelerative force. For sound cows the maximum accelerative force (MAF) and the maximum decelerative force (MDF) were of the same order of magnitude, while those for lame animals were generally modified. Forces applied to the non-lame limbs of lame cows were also changed, probably to reduce further the loads exerted upon the lame foot. PMID- 2920274 TI - The relationship between milk yield and cystic ovarian disease in cattle. AB - Studies were conducted to understand the relationship, if any, between the amount and pattern of milk yield and the occurrence of cystic ovarian disease (COD) in dairy cattle. More than 70 cows with cysts were compared with herd mates of similar lactation number. Total milk yield in lactations when cysts occurred and in the preceding lactations were not different from the corresponding lactations in control cows. Patterns of monthly milk yield did not differ between the two groups of cows. However, weekly analysis in early lactation revealed differences. Both groups of cows achieved peak yields at a similar time (5.4 +/- 1.2 vs 5.7 +/ 1.9 weeks post partum in normal vs cows with COD). However, owing to an early decline in yield of cows with COD, their duration of peak yield was significantly shorter (P less than 0.05) than in the control cows (3.2 +/- 2.2 vs 5.6 +/- 2.4 weeks). Both the attainment and the decline of peak yield occurred 5.6 (range = 2 15) weeks before the cysts were diagnosed. It is concluded that COD is not particularly a disease of higher yielding cows and that COD has no discernible effect on the milk yield or its pattern. It is speculated, however, that some cows in early lactation, while trying to meet the requirements of sustained peak milk production, are more susceptible to minor environmental changes (such as new social interactions, or changes in diet). These events may lead to a drop in milk production and disruption of events controlling normal ovulation, resulting in the formation of ovarian cysts. PMID- 2920275 TI - Ethological aspects of leg fractures in deep litter laying chickens. AB - Unilateral leg fractures in chickens on deep litter were investigated when 15 cases (0.21%), all hens, had occurred during 40 weeks and ethological factors were suspected. A significant subsequent reduction to three cases in 33 weeks followed advice to farm staff on their footwork and the avoidance of sexually crouching hens. PMID- 2920276 TI - Effect of ivermectin on the ear mange mite, Psoroptes cuniculi, of rabbits. AB - Rabbits, naturally infected with ear mange mite, Psoroptes cuniculi, were injected subcutaneously with a single dose of ivermectin at 200 micrograms or 400 micrograms/kg of body weight. The effect of the drug was evaluated clinically and parasitologically over 4 weeks. The animals in both groups became negative for mites 6 days after treatment and remained so until the end of trial. The ear lesions disappeared in both groups. However, the regression of lesions was faster in rabbits administered 400 micrograms/kg of ivermectin. PMID- 2920277 TI - Studies on the prevalence and laboratory transmission of fascioliasis in animals in the Kashmir Valley. AB - In Kashmir, 85.1% of cattle, 51.3% of sheep and 14.8% of goats were found infected with Fasciola spp. The prevalence rate varied from 66.6 to 100.0%, 25.0 to 100% and nil to 66.0% in cattle, sheep and goats respectively in different months of the year. Fasciola gigantica was the predominant species in all animal species but sheep harboured both F. gigantica and F. hepatica. The prevalence of F. hepatica infection in sheep happens to be the first report from India. Lymnaea auricularia sensu stricto supported the development of F. gigantica under laboratory conditions. The incubation temperature affected the shedding of the cercariae. Snails maintained at 25-27 degrees C started cercarial shedding as early as day 20 post-infection (PI), whereas those maintained at 10-12 degrees C commenced it from day 64 PI. One out of three experimentally infected guinea pigs aged 1 month revealed adult flukes in the liver at necropsy on day 52 PI. PMID- 2920278 TI - Effect of tetrathiomolybdate administration on the excretion of copper, zinc, iron and molybdenum in sheep bile. AB - The copper (Cu), zinc (Zn), and iron (Fe) excreted daily in the bile of three sheep were estimated at 0.20, 0.10 and 0.36 mg respectively. Intravenous administration of tetrathiomolybdate (TM) increased bile Cu excretion and reduced liver Cu concentration. Tetrathiomolybdate had no significant effect on the excretion of Zn and Fe. These findings indicate that at least one of the mechanisms by which TM induces hypocuprosis is by increasing biliary Cu excretion. Hence it has a possible use in the treatment of Cu storage diseases in man and animals. PMID- 2920279 TI - A retrospective study of hepatic abscesses in goats: pathological and microbiological findings. AB - Post-mortem examination of 658 goats showed that 17 (2.5%) exhibited hepatic abscesses. The following bacteria were isolated: Corynebacterium pseudotuberculosis (58.9%), Escherichia coli (11.8%), Corynebacterium sp. (11.8%), Pasteurella haemolytica (5.9%), Proteus sp. (5.9%) and Staphylococcus aureus (5.9%). Hepatic abscesses occurred more frequently in adult animals. Eleven of the 17 goats (64.7%) were older than 12 months of age. Four goats (23.5%) were 12 months of age and only two (11.8%) were less than 1 year of age. All of the goats with hepatic abscesses were in poor nutritional condition and the abscesses were invariably associated with accompanying pathological disorders at other body sites. PMID- 2920280 TI - Abattoir condemnation of pigs and its economic implications in Singapore. AB - Losses due to mortality and rejection of carcases and viscera in a population of 2,959,607 pigs admitted for slaughter in Singapore abattoirs between 1984 and 1986 were studied. Mortality losses were 2822 pigs (9.5 per 10,000 admissions) while 3039 whole carcases (10.3 per 10,000 admissions) were condemned at post mortem examination. The main reason for rejection of carcases was pyaemia (30.3%). Kidneys and livers were the two main organs of economic value rejected. Rejection of kidneys was primarily due to nephritis (54.8%) while liver condemnation was mainly due to cirrhosis (38.6%). The financial loss from abattoir rejection was S$5.27 millions or S$1.78 per pig admitted. The value of abattoir condemnation data as a tool in preventive medicine is discussed. PMID- 2920281 TI - Serum biochemistry of Zebu bulls and their Friesian crosses fed two planes of protein. AB - Twenty-one Bunaji (White Fulani, Zebu) and 21 Friesian X Bunaji cross-bred bull calves, approximately 6 months of age, were each divided after weaning into two groups and fed isocaloric rations containing 14.45% (high protein) and 8.51% (low protein) crude protein for 10 months. Serum samples were collected biweekly for 10 months and analysed for serum proteins. Age had no significant effect. The Bunaji had significantly (P less than 0.05) higher total protein, albumin, and alpha 1-globulin than Friesian X Bunaji. While there was no significant difference in body condition score between the two breeds, the Friesian X Bunaji had a significantly (P less than 0.05) higher growth rate. Animals on high protein diets had significantly (P less than 0.05) higher total protein, albumin, alpha 2-globulin, gamma-globulin and total globulin than those on low protein. However, alpha 1-globulin and beta-globulin were not significantly (P greater than 0.05) different for the two treatment groups. PMID- 2920282 TI - Dermoid cysts in camels. AB - In our experience the camel (Camelus dromedarius) seems to be affected more commonly by dermoid cysts as compared to other cutaneous cysts. However, apart from one reference (Monteverde, 1935), the dermoid cyst has not been reported in the camel. This report documents dermoid cysts in identical locations in 11 camels with two camels having bilateral dermoid cysts at the similar site. PMID- 2920283 TI - Postaccess processes in the open vs. closed class distinction. AB - We present the results of two auditory lexical decision experiments in which we attempted to replicate findings originally presented in Bradley (1978, Computational distinctions of vocabulary type, Ph.D. dissertation, MIT). The results obtained by Bradley were used as evidence for a processing distinction between the open and the closed class vocabularies; this distinction then used as part of an explanation for agrammatism in the comprehension and production of Broca's aphasics. In our first experiment we failed to replicate Bradley's result of frequency insensitivity in the closed class. Our second experiment, however, replicates Bradley's finding that closed class based nonwords (e.g., thanage) fail to induce interference effects in nonword decisions. We argue that our results, together with the various other reported failures to replicate Bradley's frequency insensitivity result, indicate that the open and closed classes may play distinct roles in postaccess phenomena involving the processing of morphological information but that such studies cannot address the question of whether the open vs. closed class distinction plays a role in syntactic processing. PMID- 2920284 TI - Immediate memory functions in reading disability subtypes. AB - This study examined immediate memory processes in specific reading disability subtypes. Three subgroups (n = 15 in each subgroup) of reading disabled children were examined: (a) perceptual-motor disorder, (b) verbal disorder-general, and (c) verbal disorder-specific (memory). The three groups were matched for age and full scale IQ. All children received a memory-for-colors task (Color Span Test) designed to evaluate intra- and intermodal serial memory functioning. Comparison of memory profiles for the three reading disability subtypes revealed that patterns varied depending on mode of stimulus presentation or response. Although all three groups performed considerably below normative levels on each of the four subtests of the Color Span Test, all subjects performed significantly better on verbally presented items than on visually presented items. The findings were interpreted to suggest that these reading disabled children may not consistently utilize verbal strategies for coding or retrieval of information when stimuli are visually presented. PMID- 2920285 TI - The effects of right and left hemiparkinsonism on prosody. AB - Recent studies show right hemisphere dominance in the mediation of emotional prosody and left hemisphere contribution to linguistic prosody in patients with cortical injury. The present study investigated emotional and linguistic functions of prosody as well as facial and musical processing in 21 patients with lateralized subcortical disease. Fourteen right hemiparkinsonians (RPD) and 7 left hemiparkinsonians (LPD) were compared to 17 normal controls (NC). Patients were impaired on receptive and expressive tests of emotional and linguistic prosody. Patients were also selectively impaired on emotional processing of facial stimuli and in the musical processing of pitch and tonal memory, though not timber. These findings suggest that monotone speech reported in PD is of multimodal origins and may involve dysfunction in neural centers involved in emotional and linguistic processing. There were no differences between RPD and LPD groups in the pattern of deficits, suggesting bilateral involvement in emotional processing at the subcortical level. PMID- 2920286 TI - Cortical deafness cannot account for the inability of Japanese macaques to discriminate species-specific vocalizations. AB - Bilateral ablation of the superior temporal gyrus in Japanese macaques results in a significant hearing loss (cortical deafness) as well as in an inability to discriminate between two types of their "coo" vocalizations. A two-part investigation was conducted to determine whether the hearing loss may itself affect the ability to discriminate vocalizations. First, four normal Japanese macaques were tested for their ability to discriminate coos which were filtered to simulate the effect of a cortical hearing loss. Second, four Japanese macaques with bilateral superior temporal gyrus lesions were tested for their ability to discriminate coos which were amplified and equalized to compensate for each animal's hearing loss. All four normal macaques were able to discriminate the filtered coos easily whereas compensating for the operated monkeys' hearing losses did not improve their performances. It appears that the inability of monkeys with bilateral superior temporal gyrus lesions to discriminate conspecific vocalizations is not simply due to the accompanying hearing loss, but is a separate auditory disorder. PMID- 2920287 TI - Sequence initiation performance by stutterers under conditions of response competition. AB - Male stutterers and nonstutterers were compared on their performance of a task that required tapping keys as rapidly and accurately as possible to reproduce different sequences of finger movements as soon as they had been demonstrated on a visual display panel. Testing using the right hand alone confirmed previous findings that stutterers are significantly slower than nonstutterers in initiating new movement sequences and make significantly more errors on initial sequences. Subjects were also tested on this sequence reproduction task while they performed concurrently a manual task with the left hand that required turning a knob in response to signal tones. The hypothesis underlying the study was that associated with stuttering is a dysfunction in the mechanisms regulating interhemispheric communication, and it was predicted that the concurrent task would interfere more with the sequence reproduction task performance of stutterers than with that of nonstutterers. A joint analysis of the speed and accuracy aspects of performance of the two tasks confirmed the prediction. Additional research required to clarify whether the effects are in fact due to the hypothesized interhemispheric mechanisms or to a generally greater susceptibility of stutterers to interference from any concurrent motor or cognitive activity is discussed. PMID- 2920288 TI - The effect of semantic and syntactic structure on verbal memory in Alzheimer's disease. AB - This study examined the ability of 17 patients with Alzheimer's disease and 17 normal-old subjects to recall short sentences that were normal, or had a disruption in either their semantic structure, their syntactic structure, or both their semantic and syntactic structure. Results showed that sentence recall performance was affected similarly in the demented and normal-old subjects by both the syntactic and semantic structure of the sentences. The presence of either type of language structure appeared to allow both normal and demented subjects to organize strings of words into multiword chunks for more efficient memory encoding. PMID- 2920289 TI - Semantic abilities in dementia of the Alzheimer type. 1. Lexical semantics. AB - The lexical semantic abilities of 18 Alzheimer patients were investigated using confrontation naming tasks (including both visual and tactile naming tests) and compared to those of a group of institutionalized, nonneurologically impaired control subjects matched for age, sex, and educational level. The Alzheimer patients produced a greater number of naming errors than the control subjects. The errors made by subjects during the naming tasks were analyzed according to a set of 16 error response types. The Alzheimer patients' response patterns suggest that they do recognize objects which they are unable to name and are able to identify the semantic class to which the target belongs, but cannot provide the lexeme corresponding to the correct individual class member. The results support a semantic network disruption rather than a visual perceptual deficit as the basis of the naming disturbance observed in Alzheimer patients. PMID- 2920290 TI - Processing of lexical ambiguities: a comment on Milberg, Blumstein, and Dworetzky (1987). AB - In a study by Milberg, Blumstein, and Dworetzky (1987), normal control subjects and Wernicke's and Broca's aphasics performed a lexical decision task on the third element of auditorily presented triplets of words with either a word or a nonword as target. In three of the four types of word triplets, the first and the third words were related to one or both meanings of the second word, which was semantically ambiguous. The fourth type of word triplet consisted of three unrelated, unambiguous words, functioning as baseline. Milberg et al. (1987) claim that the results for their control subjects are similar to those reported by Schvaneveldt, Meyer, and Becker's original study (1976) with the same prime types, and so interpret these as evidence for a selective lexical access of the different meanings of ambiguous words. It is argued here that Milberg et al. only partially replicate the Schvaneveldt et al. results. Moreover, the results of Milberg et al. are not fully in line with the selective access hypothesis adopted. Replication of the Milberg et al. (1987) study with Dutch materials, using both a design without and a design with repetition of the same target words for the same subjects led to the original pattern as reported by Schvaneveldt et al. (1976). In the design with four separate presentations of the same target word, a strong repetition effect was found. It is therefore argued that the discrepancy between the Milberg et al. results on the one hand, and the Schvaneveldt et al. results on the other, might be due to the absence of a control for repetition effects in the within-subject design used by Milberg et al. It is concluded that this makes the results for both normal and aphasic subjects in the latter study difficult to interpret in terms of a selective access model for normal processing. PMID- 2920291 TI - Reaction time methodology and the aphasic patient: a reply to Hagoort (1988). AB - P. Hagoort (1988, Brain and Language, 36, 335-348) suggests that the results of an experiment conducted with aphasic patients reported by W. Milberg, S. E. Blumstein, and B. Dworetzky (1987, Brain and Language, 31, 138-150) are "difficult to interpret in terms of a selective access model for normal processing because of a confound caused by the use of repeated lexical decision targets." We argue that the use of repeated lexical decision targets and other methodological compromises are necessary for using the lexical decision reaction time paradigm with aphasic patients. Furthermore, the minor differences between our data and those presented by Hagoort do not undermine our claims concerning semantic processing in different subgroups of aphasics, nor our comparisons of these patients to normal subjects. PMID- 2920292 TI - Immunological, psychological and sociological studies in alcohol abusers and long term abstainers. AB - The presented results are part of a broader study of problems of alcoholism investigated within the research project on "Pathogenesis of Major Mental Diseases". The paper consists of three parts: immunovirological, psychological, and sociopsychological. Certain signs of disbalance were found in the immune system of 196 alcoholics, as compared with 363 controls, which proved reversible with the improvement of the patient's condition. This may be interpreted as an additional sign of recovery of the somatic condition of the patient. In the psychological part screening questionnaires were adapted and used in 335 inpatients and 116 outpatients. In a pilot study the pesonality characteristics of 30 obtaining alcoholics were compared with those of 37 treated alcoholics. A scale of psychic rigidity was elaborated for alcoholics (130 subjects) as compared to controls (70 subjects). The sign of psychic rip6dity was evaluated for its suitability in discriminating between alcoholics and non-addict drinkers. In the sociological part diagnostic lists were elaborated containing 195 markers reflecting different aspects of the sociopsychological profile of persons at risk and of alcohol abusers. The investigated subjects came from a factory community. PMID- 2920293 TI - [The effect of trigeminal zone irritation on parameters of forced vital capacity in humans]. AB - In 44 healthy males aged 18-21 years, the authors studied the effect of irritation of the trigeminal zone by ammonia vapors and by immersion of the face into water on parameters of forced vital capacity. Inhalation of ammonia immediately induced impairment of all the studied parameters of forced expiration. In the later time intervals (up to the 10th minute after inhalation) the air flow remained reduced over the whole forced expiration (FVC/FET), mainly at the expense of decreased air flow at the end of forced expiration (FEF75-85%). Inhalation of ammonia also resulted in abolition of the psychically induced higher heart rate and in its normalization. Immersion of the face into cold water caused reduction in the values of FVC, FEV1, FVC/FET, and FEF0-25%. After voluntary apnea in the air there was only a small reduction of FEF0-25%. In the light of these findings, the authors consider irritation of cold receptors of the face to be the main cause of the changes in functional parameters of the lungs during immersion reflex. PMID- 2920294 TI - [Use of suprasternal imaging with 2-dimensional echocardiography in adults]. AB - The authors demonstrate the justification of the suprasternal approach from the hollow of the neck in routine two-dimensional echocardiographic examination in adult patients. Echocardiographic and angiographic imaging is documented in two patients after surgery for coarctation of the aorta, with the narrowed section of the arch of the aorta well visualized, and in the third patient with partial anomalous opening of the pulmonary veins, the dilated left innominate vein draining blood from the left vertical vein into the dilated upper vena cava was clearly visible. PMID- 2920295 TI - [Paroxysmal march hemoglobinuria--a 1-year duration in a young man]. AB - The development of paroxysmal march hemoglobinuria in a young man is described. It first appeared when he was 31 years old and lasted for over one year. It was induced only by long walking (half an hour and more) on paved city streets and did not appear after any other physical exertion. Apart from the dark urine, the condition had a completely asymptomatic course and after one year it spontaneously disappeared. The practical implication of differentiating hemoglobinuria from other potential causes resulting in dark coloration of urine, such as hematuria, porphyrinuria and myoglobinuria, is being emphasized. The discussion presents a concise analysis of the problem of hemolysis developing as a result of mechanical damage to erythrocytes, particularly with regard to paroxysmal march hemoglobinuria. (Ref. 18.). PMID- 2920296 TI - Use of selected quantitative parameters of the electric field of the heart in evaluating the presence and site of preexcitation. AB - Electrocardiographic methods play a decisive role in evaluation of the health condition of subjects with WPW pattern. The authors examined 54 patients with WPW pattern with different degrees of preexcitation. The presence of preexcitation and the localization of its focus was determined by surface electrocardiographic mapping using the original Czechoslovak computer equipment KARDIO-SMEP 01.0. The duration of ventricular activation was determined according to root mean square signals. By means of potential and temporo-spatial analysis of peak negative regions of instantaneous maps (in 2 ms intervals) they determined the duration of the period of proper preexcitation, of fusion of the two activation events, and of the end depolarization of the ventricles. In localizing the preexcitation focus they proceeded according to the criteria of Benson et al. (1982) with individual evaluation of quantitative preexcitation parameters of ECG maps and according to vector analysis of the delta wave. Quantitative and temporo-spatial evaluation of the mutual relationship of the two activation events in WPW pattern allows to establish reliably the presence, degree and focus localization of preexcitation even at a low degree of preexcitation and at a low-potential level of the preexcitation surface activity on ECG maps. PMID- 2920297 TI - Genotoxic effects of heavy metals in rat hepatocytes. AB - The genotoxic interaction of metals, which are common environmental contaminants, was studied in cultured hepatocytes. Freshly isolated rat hepatocytes were exposed to concentrations of cadmium, copper, silver and lead salts ranging from non-cytotoxic to moderately cytotoxic (as determined by LDH release), and the incorporation of [3H]thymidine into the DNA, as a measure of repair synthesis, was followed. In addition, the uptake of metals by the nuclear fraction was determined using Inductively Coupled Plasma/Mass Spectrometry or atomic absorption spectrophotometry. The evaluation of binding of 109Cd to the DNA in situ was also attempted. It was observed that after a 20 h exposure period, all the metals investigated were found in the nuclear fraction of hepatocytes, with Ag apparently being accumulated less efficiently. In parallel, Cd (0.18 to 1.8 microM) and Cu (7.9 to 78.5 microM) consistently produced a statistically significant stimulation of [3H]thymidine incorporation into the DNA, in the presence or absence of hydroxyurea while Ag was active only at the highest concentration tested (18.5 microM). In contrast, Pb failed to induce a UDS response at the levels used. Moreover, exposure of hepatocytes to 1.8 microM 109CdCl2 for 20 h led to a DNA binding ratio of 0.98 +/- 0.23 ng Cd/micrograms DNA. The present results support the view that the nucleus may be an important target organelle for metal toxicity. PMID- 2920299 TI - Effects of tetradecanoyl phorbol acetate, pyrethroids and DDT in the V79. AB - The effects of the pyrethroids flucythrinate, cyfluthrin, bioallethrin and resmethrin on metabolic cooperation between V79 cells were investigated. Addition of flucythrinate to cocultures of 6-thioguanine-resistant and 6-thioguanine sensitive V79 cells significantly increased the mutant cell recovery, indicating inhibition of intercellular communication. No such effect was observed by the other pyrethroids tested. To compare the modes of action of TPA-, DDT-, and pyrethroid-induced inhibition of intercellular communication, co-exposure experiments were undertaken. Addition of TPA, together with increasing doses of fenvalerate or flucythrinate, produced a synergistic response. Various combinations of fenvalerate-, flucythrinate- and DDT-exposure gave results in accordance with an additive response. The result suggest different pathways of action for TPA and the insecticides investigated in this study. PMID- 2920298 TI - Synergistic inhibition of metabolic cooperation by oleic acid or 12-0 tetradecanoylphorbol-13-acetate and dichlorodiphenyltrichlorethane (DDT) in Chinese hamster V79 cells: implication of a role for protein kinase C in the regulation of gap junctional intercellular communication. AB - The effects of TPA and/or DDT and oleic acid and/or DDT on gap junction-mediated intercellular communication (i.e. metabolic cooperation) between Chinese hamster V79 cells was examined. Addition of TPA, DDT or oleic acid alone to cocultures of 6-thioguanine-resistant (6-TGR) and 6-thioguanine-sensitive (6-TGS) V79 cells significantly increased the recovery of 6-TGR cells indicating inhibition of metabolic cooperation. In the presence of TPA and DDT or oleic acid and DDT the observed recovery of 6-TGR cells was significantly greater than the expected (calculated) additive 6-TGR cell recovery. No synergistic increases in 6-TGR cell recovery were observed when co-cultures of V79 cells were exposed to dieldrin and DDT. These results indicate that TPA and DDT or oleic acid and DDT can act synergistically to inhibit metabolic cooperation. These data suggest a role for protein kinase C in the regulation of gap junction-mediated intercellular communication. PMID- 2920301 TI - Asepsis--an indispensable part of the patient's care plan. PMID- 2920302 TI - Wound care. AB - Knowledge of wound physiology and factors that affect wound healing is extremely valuable to the critical care practitioner. Critical care patients are all inherently at risk for wound healing complications and infection. Early recognition of high-risk patients and optimization of the patient's wound healing resources can, in many cases, prevent such complications. PMID- 2920300 TI - Two models for screening chelating agents for cadmium removal. AB - The effectiveness of some chelating agents to mobilize cadmium from Chinese hamster ovary cells after chronic exposure (20 hr), as well as from cytosolic metallothionein, was studied. In the first protocol, the most effective substance was 2,3-dimercaptopropanol, followed by 2,3-dimercaptopropane-1-sulfonate and 2,3 dimercaptosuccinic acid, whereas CaNa3-diethylenetriamine pentaacetic acid X 5 H2O showed less effect. Simultaneous incubation of cells with cadmium and the chelating agent resulted in a different order of effectiveness: CaNa3 DTPA prevented cadmium uptake almost totally, 2,3-mercaptopropanol by 75% and 2,3 dimercaptopropane-1-sulfonate by 35%. Neither CaNa3-diethylenetriamine pentaacetic acid X 5 H2O nor 2,3-dimercaptosuccinic acid had altered the distribution of cadmium between the cytosolic protein fractions after a 2 hr incubation of cells, whereas after this period, 2,3-dimercaptopropanol had removed all cadmium from metallothionein, and 2,3-dimercaptopropane-1-sulfonate about 50%. None of the chelating agents had reduced the amount of Cd bound to high molecular weight proteins. In the cell-free system, 2,3-dimercaptopropanol and 2,3-dimercaptopropane-1-sulfonate were equally effective and removed all cadmium from metallothionein within ten minutes. CaNa3-diethylenetriamine pentaacetic acid X 5 H2O, however, even after 60 min, had removed only 50% of the cadmium. The remaining cadmium was found distributed to the high molecular weight and lower molecular weight protein fractions. PMID- 2920303 TI - Surveillance of nosocomial infections. AB - Surveillance for nosocomial infections is one of the most effective quality assurance outcome measurements of health care. To provide the most reliable data, organization is the key to reporting good data. Specific criteria must be defined, and where and how the necessary data is most readily available must be determined. Surveillance activity must be performed concurrently so that data can be reported in a timely manner and appropriate action can be taken if necessary. Reports must be designed in a concise and understandable manner so they are easily interpreted and can be effectively used. The method of data reporting must be analyzed, committees and individuals who need to evaluate the data must be identified, and any necessary action must be taken to ensure that data fit the evaluators' needs. The use of graphics to provide a clearer picture of consistent rates or problem areas should be evaluated. PMID- 2920304 TI - Combination of disopyramide and propranolol in hypertrophic cardiomyopathy. AB - Fifteen patients were studied by echocardiography, apexcardiogram and carotid pulse tracings in four ways: basally; on propranolol 40 mg, three times daily; on disopyramide 200 mg single dose, three days after propranolol discontinuation; and on both drugs. The following data were measured: systolic anterior mitral motion slope, systolic anterior mitral distance from the septum, outflow tract diameter, the A wave to the total apexcardiographic excursion ratio, carotid pulse contour and left ventricular ejection time index. Propranolol did not produce any significant changes while disopyramide was much more effective in changing the data in a direction suggesting diminution of left ventricular outflow gradient. The combination of propranolol and disopyramide had the greatest influence. Fourteen patients received the two drugs for 12.3 +/- 4.3 months with improvement of NYHA class. PMID- 2920305 TI - Termination of sustained ventricular tachycardia with a new antitachycardia pacemaker: role of the nonautomatic mode to follow pacemaker function. AB - The use of an antitachycardia pacemaker for the treatment of recurrent, drug resistant nonsyncopal sustained ventricular tachycardia in a 28-year-old patient is described. The report emphasizes the role of electrocardiographic recording during manual activation of the tachycardia response in an outpatient setting. The follow-up covers 12 months with 26 spontaneous tachycardia episodes forcing the patient to go to an emergency room to monitor tachycardia termination. Mean ventricular tachycardia cycle length was 340 +/- 21 ms. Tachycardias were terminated either by the primary or secondary modality without acceleration or degeneration to ventricular fibrillation. Thus, it was possible to assess the efficacy and the safety of the termination programs. Unlike during intensive in hospital testing, restoration of stable sinus rhythm was complicated by re emergence of ventricular tachycardia. It is concluded that manual activation with medical supervision provides safe management of selected patients with ventricular tachycardia. However, in-hospital testing overestimated, in this case, the efficacy of tachycardia response modalities to terminate spontaneous tachycardia episodes. The customization of an antitachycardia pacemaker with an automatic implantable cardioverter/defibrillator may increase the quality of life as it would allow switching to automatic pace termination. PMID- 2920306 TI - Congenital complete heart block in an infant with free plasma carnitine deficiency. AB - A newborn male presenting with congenital complete heart block was found to have low levels of free plasma carnitine. Among the many complications of carnitine deficiency is a structural disruption of myocardial tissue. A deficiency of carnitine may be causally related to the presence of cardiac dysrhythmias in this patient on the basis of mechanical disturbance to the cardiac conducting system. PMID- 2920307 TI - Increased calcium uptake in vascular tissue by plasma of salt induced hypertensive Dahl rats. AB - Elevated intracellular free cytosolic calcium in vascular smooth muscle cells has been suggested in the pathophysiology of hypertension and circulating factors in the plasma have been implicated. To investigate the role of these factors on calcium homeostasis in salt induced hypertension, calcium uptake was measured in aortae of Sprague-Dawley rats by plasma derived from Dahl salt sensitive and resistant rats given high (8.0%) and low (0.4%) salt diets, respectively, for four weeks. Calcium uptake was also measured in aortae of Dahl rats on these diets. Calcium uptake in aortae and systolic blood pressure were higher (P less than 0.001) in Dahl salt sensitive rats given a high salt diet as compared to those on a low salt diet. Plasma from salt sensitive rats on high salt diet increased calcium uptake (P less than 0.001) in aortae of Sprague-Dawley rats. In contrast, no changes in calcium uptake and systolic blood pressure were observed in Dahl salt resistant rats. The parallel increase in systolic blood pressure and calcium uptake in Dahl salt sensitive rats on high salt diet suggests that increased intracellular free calcium may be involved in the pathophysiology of hypertension. The increased calcium uptake seems to reflect an abnormality in calcium handling by the vessels. These data also demonstrate that plasma from salt sensitive rats on high salt diet increases calcium uptake in aortic tissue. PMID- 2920308 TI - Facts about adolescent suicide. PMID- 2920309 TI - Charting behaviors of psychiatric nursing. PMID- 2920310 TI - Therapeutic relationships in milieu therapy. PMID- 2920311 TI - Youth suicide. PMID- 2920312 TI - Biologic and structural evaluation of 80 surgically excised human umbilical vein grafts. AB - Human umbilical vein is a valuable alternative to autogenous saphenous vein in lower-limb revascularization. However, the long-term patency is not as good. To understand better the reasons for this, the authors studied the biologic and structural changes occurring in 80 segments of human umbilical vein (HUV) grafts excised from 70 patients. Morphologic, histologic and scanning electron microscopy examinations were performed on each specimen. It was noted that increasing duration of implantation was associated with greater encapsulation and less surrounding inflammatory reaction. Twenty-six percent of clinically noninfected grafts were found to harbour bacteria. Bacteremic colonization was often in the folds of the luminal surface. As a result of these findings, the authors emphasize the need for complete excision of clinically infected grafts. Anastomoses between HUV segments are discouraged because they are associated with a high frequency of infection and a corresponding decrease in duration of implantation. Delamination of the wall was common, and such sites may represent areas at risk for further degradation. Continued surveillance of the biologic and structural changes occurring in excised grafts remains an important method in increasing our understanding of the evolutive complications of HUV grafts. PMID- 2920313 TI - Extra-anatomic bypass grafting: a rational approach. AB - To determine predictors of long-term patency in extra-anatomic bypass grafting, the authors studied retrospectively the charts of 134 patients who underwent bypass grafting (axillofemoral in 17, axillobifemoral in 32 and femorofemoral in 85). Of the study group, 64% were men; the mean age was 65 +/- 12 years (+/- SEM). The indications for grafting were limb salvage (102), claudication (27) and replacement of septic grafts (5), and for using the extra-anatomic route included high risk (83), sepsis (8) and unilateral disease (34). Operative mortality was 6% and the early graft occlusion rate 7.4%. The late death rate was 44%. At 3 years, the life-table patency rates for the various procedures were axillofemoral 52.5%, axillobifemoral 67.7% and crossfemoral 86.9%. Smoking significantly (p less than 0.05) decreased the patency rate, but diabetes did not. However, amputation was more frequent in diabetics. Indications for operation did not alter patency rates, but did affect operative mortality. The authors conclude that extra-anatomic bypass grafting is highly successful, but not as successful as anatomic bypass. When appropriate, the axillobifemoral graft is preferred to the axillounifemoral graft because of its increased patency. Crossfemoral grafts must be carefully monitored to ensure that no donor limb stenosis occurs and this procedure should not be attempted unless the disease is truly unilateral. PMID- 2920314 TI - Abdominal aortic aneurysm: consequences of a positive family history. AB - To assess the prevalence of coexisting abdominal aortic aneurysm (AAA) within certain families, a retrospective review was carried out of patients who had undergone AAA repair over a 5-year period. Contact was made with 305 families (52%) and a positive history of an affected, first-degree relative was obtained in 34 (11%). A known AAA was reported to affect approximately 20% of siblings at risk when the proband had an affected parent or sibling. Siblings of patients with an affected first-degree relative represent a high-risk group that may benefit from a screening program for earlier detection and elective management of AAA. PMID- 2920315 TI - Transiliac bypass for infected femoral end of an aortofemoral graft. AB - Infection of an aortofemoral fabric graft is among the most serious complications of vascular surgery and necessitates removal of the graft. The authors chose a transosseal (iliac bone) approach to permit a new graft to be carried down to the periphery without the risk of contamination or pressure on it from the patient's position. They performed this procedure in a 71-year-old man. He underwent a transiliac bypass before the infected limb of an aortobifemoral graft was removed. He was well 11 months after the operation and the graft was functioning well with no evidence of infection. PMID- 2920316 TI - Renal oncocytoma in pregnancy: a case report. AB - Oncocytoma is an uncommon renal tumour and this is the first report of such a tumour occurring in a pregnant woman. Optimal treatment is nephrectomy and the prognosis is usually good, though metastasis has been reported. It is unknown whether pregnancy alters tumour behaviour or the prognosis. PMID- 2920317 TI - Failure of preoperative cultures to predict development of Staphylococcus aureus wound infections after cardiac surgery. AB - To assess the predictive value of preoperative surveillance cultures for the postoperative development of Staphylococcus aureus wound infection, the findings in 563 patients who underwent elective cardiac surgery were evaluated. One hundred and forty-seven (26%) were found to be S. aureus carriers preoperatively. Postoperatively, 11 S. aureus wound infections developed, 4 in patients whose cultures were positive preoperatively and 7 in patients whose cultures were negative preoperatively. The patient's endogenous flora appears to be the source of only a minority of such postoperative infections. The authors conclude that preoperative surveillance cultures are not of value in predicting patients at risk for wound infection after elective cardiac surgery. PMID- 2920318 TI - Incidence and importance of bacteriuria in postoperative, short-term urinary catheterization. AB - The frequency and importance of bacteriuria in patients requiring short-term postoperative catheterization (24 to 48 hours) is unknown. From a prospective, controlled study of 100 patients requiring catheterization postoperatively, the authors determined that there was a definite risk (6%) of bacteriuria; however, a symptomatic urinary tract infection developed in only 1% of the patients. There was no advantage to using either a latex or silicone catheter. It appears that the risk of symptomatic bacteriuria in this group of patients is very low when a closed urinary drainage system is used under strict, sterile conditions of catheter insertion and with meticulous ongoing catheter care. PMID- 2920319 TI - Synovial cyst of the hip: an unusual cause of an inguinal mass. AB - A palpable groin mass is a common surgical problem. The authors describe the case of a 58-year-old man who had a painless right groin mass. Initial clinical evaluation suggested a femoral hernia. Subsequent radiologic evaluation revealed a synovial cyst of the hip. Awareness of this anomaly will aid early diagnosis and influence treatment. PMID- 2920320 TI - Primary anterior mediastinal tumours: "an investigational algorithm". AB - A review of 33 months' experience with primary anterior mediastinal masses in 31 patients disclosed that in 9 (29%) the tumour was benign. Nineteen (86%) of the 22 malignant tumours and only 2 of the 9 benign tumours were symptomatic. Diagnosis was established by histopathologic examination of a biopsy specimen or resected tissue and serum radioimmunoassay for alpha-fetoprotein or human chorionic gonadotropin, beta-subunit. The authors present an investigational algorithm, using modern procedures, to facilitate the diagnosis of this relatively uncommon and challenging condition. PMID- 2920321 TI - Unusual gastric foreign bodies. PMID- 2920322 TI - Doctor or mister? PMID- 2920323 TI - Stapled bypass procedure for unresectable pancreatic carcinoma. PMID- 2920324 TI - Perforated benign gastric ulcer: the case for simple closure. AB - During the 12 years from 1975 to 1986 at University of Alberta Hospital, Edmonton, 36 patients were found to have a perforated gastric ulcer. A review of their operative treatment revealed that only one patient had a definitive gastric resection despite reports in the literature recommending the procedure. This study was undertaken to determine if simple closure was appropriate treatment for the majority of these patients. Even the enthusiasts of gastric resection would agree that advanced patient age, serious underlying disease and delay in treatment are contraindications to the procedure for perforated gastric ulcer. We found that 28 (78%) of the 36 patients had one or more of these contraindications. Thus, the high-risk nature of the patients presenting to our institution with perforated gastric ulcer explains the frequent use of simple closure in these cases. The data from this study indicate that the profile of patients presenting with perforated benign gastric ulcer needs to be defined before generalizations regarding surgical treatment are made. PMID- 2920325 TI - Care in the air. PMID- 2920326 TI - Funds for health care: new source? PMID- 2920327 TI - Induced abortion: the CMA's position. PMID- 2920328 TI - Letting patients know where you stand. PMID- 2920330 TI - Gastrointestinal gas. PMID- 2920329 TI - The Hippocratic Oath. PMID- 2920331 TI - Unusual cause of carpal tunnel syndrome. PMID- 2920332 TI - Promotion of infant formula and feeding products. PMID- 2920333 TI - Getting help for depressed colleagues. PMID- 2920334 TI - Research in obstetric care: questions and methods. PMID- 2920335 TI - Understanding physicians' response to AIDS. AB - Attempts to comprehend physicians' extreme reaction to AIDS (acquired immune deficiency syndrome) have met with great difficulty since the disease brings into question traditional norms and assumptions. As the medical profession struggles to develop guidelines and policies to help it deal with this disease, it can draw on very little systematic research on the effect of AIDS on physicians' attitudes and practices. We suggest a framework developed from the literature on physicians' and society's response to other disorders that would provide a basis for organizing the ever-increasing amount of information on physicians and AIDS and would guide systematic research aimed at understanding and predicting physicians' participation in the prevention and management of AIDS. Within this framework we consider how characteristics of the disease, elements of the health care system and physicians' attitudes interact to influence clinical and personal practices. AIDS had led to new delineations of physicians' responsibility, modification of prevailing beliefs about physician autonomy and thus a redefinition of the role of the physician in North America. PMID- 2920336 TI - Differences in intrapartum obstetric care provided to women at low risk by family physicians and obstetricians. AB - To determine differences in practice style and to examine maternal and neonatal outcomes, we reviewed the hospital charts of 1115 women admitted by family physicians and 1250 women admitted by obstetricians who gave birth at one of three teaching hospitals in Toronto between April 1985 and March 1986. All the women in the two groups were categorized retrospectively as being at low risk at the onset of labour on the basis of their prenatal records and their admission histories and physical examination results. There were higher proportions of younger women and women of lower socioeconomic status in the family physician group than in the obstetrician group (p less than 0.001). The rates of interventions, including artificial rupture of the membranes, induction, augmentation, low forceps plus vacuum extraction, episiotomy and epidural anesthesia, were all higher in the obstetrician group. The mean birth weight and the cesarean section rate were the same in the two groups. Differences in labour and delivery outcomes between the two groups, including a higher rate of spontaneous vaginal delivery for the family physicians, reflected a more "expectant" practice style by family doctors. However, there were no significant differences in the rates of maternal or neonatal complications. A practice style characterized by a higher rate of interventions was not associated with improved maternal or newborn outcome in this low-risk setting. PMID- 2920338 TI - Sterilization: Canadian choices. AB - Significant differences in cost and safety between vasectomy and tubal ligation have been reported. For this reason the incidence of these two procedures between 1976 and 1986 was studied to obtain information upon which future policy decisions might be based. Although tubal ligation predominated in almost every province and year its rate declined by 27.6% over the study period, whereas the rate of vasectomy increased by 39.1%. When projected to 1988 the national rates for the two procedures became nearly equal; those for Quebec had become equal by 1986. Provincial differences were most marked in eastern Canada, where neighbouring provinces had the highest and the lowest rates of sterilization in the country. Given the relative economic and surgical disadvantages of tubal ligation, policymakers may wish to consider fostering an increased acceptance of vasectomy, particularly in areas where such acceptance continues to be slow. PMID- 2920337 TI - Relation of family physician or specialist care to obstetric interventions and outcomes in patients at low risk: a western Canadian cohort study. AB - To determine the relation of family physician or specialist care to intrapartum interventions and outcomes, we carried out a historical cohort study of 1456 obstetric patients at low risk admitted between Nov. 15, 1984, and Mar. 15, 1986, to a western Canadian teaching hospital. The patients were classified as being at low risk on admission by means of chart review. Family physicians and specialists were found to have similar rates for most of the interventions measured, although the interventions for which significantly different rates were found suggest a less interventionist style of intrapartum care by family physicians. There were no significant differences in maternal or neonatal outcomes except for a higher proportion of infants weighing less than 2500 g among primigravid women cared for by family physicians compared with those under the care of specialists. Self selection of physician specialty by patients resulted in differences in the demographic characteristics of the two patient populations. The findings support the continued involvement of family physicians in the provision of obstetric care. PMID- 2920340 TI - The primacy of diet in the treatment of hyperlipidemia. PMID- 2920339 TI - Massive necrosis of fat and skin as complication of obesity. PMID- 2920341 TI - Georgia survey results are bleak news for AIDS educators. PMID- 2920342 TI - The doctor as medical entrepreneur: there are still MDs willing to take the plunge. PMID- 2920343 TI - Medicine in Uganda: the impact of prolonged war and epidemic AIDS on medical care. PMID- 2920344 TI - Art-related health hazards: artists should be put in picture. PMID- 2920345 TI - Ottawa's geriatric assessment program: "better care is less expensive care". PMID- 2920346 TI - Is the house call coming back? Did it ever leave? PMID- 2920347 TI - Alzheimer's research: physicians begin to tread in an ethical minefield. PMID- 2920348 TI - Do you love this planet? PMID- 2920349 TI - AIDS and the arts: the iconography of an epidemic. PMID- 2920350 TI - Geriatric dermatology. PMID- 2920351 TI - Aging of the United States population. The dermatologic implications. AB - Clearly in the near and later future the older patient will augment significantly the burden of dermatologic disease and the consequent need for care. Increasing in numerical strength, those 65 years and older, carrying along the common problems prevalent in every adult age group, will, by living longer, have new problems related to wear, tear, and actinic exposure as well as pharmacologically induced problems arising from needed therapy for other conditions. The predictable challenge to our specialty is formidable. PMID- 2920352 TI - The case for a name change from neoadjuvant chemotherapy to induction chemotherapy. PMID- 2920353 TI - The social implications of questionable cancer therapies. AB - Questionable or "unorthodox" treatments are not selected in a vacuum; their degree of popularity and the particular types used are functions of their social and cultural context. The liquid preparations that were popular earlier in this century reflected fascination with bottled medicinals, consistent with the growing era of pharmaceutical medicine. Today's questionable remedies are similarly consistent with their social and cultural context. "Metabolic" therapies emphasizing diet, self care, vitamins, and internal cleansing, along with "immune-enhancing" regimens, represent today's reigning "alternatives." Such approaches reflect underlying social trends and values, such as belief in assuming personal responsibility for one's health, the importance of self care and physical fitness, patients' rights movements, dietary emphases encouraged by conventional and alternative medicine alike, the holistic medicine movement, and general disaffection with organized medicine. Just as questionable therapies are born of the values and beliefs of their culture, so these treatments and their use affect the social environment in which they exist. The relationship is reciprocal and cyclic, with social trends encouraging particular forms of questionable regimens and these regimens, in turn, reinforcing prevailing social beliefs. Public beliefs about cancer were reflected in responses to our studies of unorthodox cancer therapies and of psychosocial correlates of survival. Responses revealed widely held values and beliefs about cancer, cancer treatment, and medicine generally. These themes are described. PMID- 2920354 TI - Treatment of alpha chain disease. Results of a prospective study in 21 Tunisian patients by the Tunisian-French intestinal Lymphoma Study Group. AB - Between 1981 and 1985, the authors studied 21 Tunisian patients with alpha chain disease. Twenty of 21 underwent laparotomy. According to Galian et al. six patients were classified Stage A, two Stage B, and 13 Stage C. The therapeutic regimen included the following: (1) Antibiotics: In the case of intestinal bacterial overgrowth (IBO), antibiotics selected by their antibiograms were delivered; in absence of IBO, metronidazole plus ampicillin were first given. The antibiotic treatment was changed in case of therapeutic failure. (2) Chemotherapy: From 1981 to 1983 a cyclophosphamide, Adriamycin (doxorubicin), teniposide (VM-26), prednisone (CHVP) protocol (Adriamycin 35 mg/m2, teniposide 50 mg/m2 day 2, cyclophosphamide 300 mg/m2 days 2 through 4, prednisone 40 mg/m2 days 1 through 10) was used. After 1983 bleomycin 15 mg, Adriamycin 30 mg, vinblastine 10 mg were given on day 15. Serum immunoelectrophoresis and immunohistochemical study of duodenojejunal specimens were made on a 3-month and 6-month basis, respectively. Survival curve analysis was made according to Kaplan and Meier. Results were as follows: (1) Stage A: Six patients were first treated by antibiotics alone; two complete responses (CR) persisting 42 and 55 months later were observed, respectively. The four antibiotic failures were submitted to further chemotherapy with four subsequent failures and two deaths. (2) Stage B-C: Chemotherapy led to nine CR with one precocious relapse, a salvage chemotherapy allowing to one more CR. (3) All stages mixed, percentage of survival reached 90 +/- 12% at 2 years and 67 +/- 25% at 3 years, all patients alive beyond 3.5 years being disease-free. PMID- 2920355 TI - Tamoxifen treatment increases the concentration of 52K-cathepsin D and its precursor in breast cancer tissue. AB - The pro-cathepsin D of Mr 52,000 is regulated by estrogens via the estrogen receptor (RE) and is secreted by breast cancer cells in vitro. In an attempt to predict the hormone responsiveness of breast cancer in vivo, we have assayed total 52K cathepsin D and its precursor in the primary breast cancer cytosol of 36 patients treated before surgery with 30 mg of tamoxifen daily for 1 to 5 weeks (average, 3 weeks). Compared to a similar control population, total 52K cathepsin D was increased by tamoxifen (P = 0.02) but less so than its precursor (P less than 0.001). Furthermore, 45% of the RE-positive tumors from tamoxifen-treated patients had a higher cathepsin D precursor concentration than the same type of tumor from control patients, or than RE-negative tumors from tamoxifen-treated patients. This 3-week challenge test was probably too short to avoid partial estrogenic activity of tamoxifen (flare) and the authors infer that longer time of treatment would decrease rather than increase the concentration of cathepsin D in the RE-responsive tumors. However, two cancers from patients with relapses after prolonged tamoxifen treatment (greater than 6 months) also had high concentrations of 52K cathepsin D and its precursor. The authors conclude that the concentration of cathepsin D and its precursor in breast cancer cytosol can be increased by short-term tamoxifen treatment, suggesting that these tumors are estrogen responsive. PMID- 2920356 TI - 4-epidoxorubicin in recurrent cervical cancer. AB - Thirty-eight patients with histologically proven recurrent cervical cancer were treated with epirubicin, an analogue of anthracycline. There were eight complete responders and ten partial responders. The overall response rate was 47.8%. The survival duration of the responders was significantly longer than that of the nonresponders. The optimal dose of epirubicin has yet to be determined. The dosage of 120 mg/m2 was well tolerated. The role of epirubicin as an adjuvant chemotherapeutic agent in the treatment of cervical cancer was discussed. PMID- 2920357 TI - Factors affecting the response of recurrent squamous cell carcinoma of the cervix to cisplatin. AB - From June 1977 to June 1987 74 patients were treated with cisplatin for recurrent squamous cell carcinoma of the cervix as the primary chemotherapeutic agent. Sixty-eight patients were evaluable for response or survival. Patients with disease confined to the chest had a 53% complete response rate with an overall response rate of 73%. Patients with localized pelvic recurrences or persistence demonstrated no complete responses and a 21% overall response rate. Isolated chest metastases are more likely to respond to cisplatin than pelvic recurrences (P = 0.0007); however, location of recurrence did not significantly alter survival (mean 22.7 months versus 14.1 months; P = 0.24.). Concomitant disease in other locations reduced the likelihood of response in the chest (P less than 0.05) by virtue of lack of response in those other sites. Lesion size, clinical stage, patient age, and duration from primary treatment to recurrence were not of significance with regard to response or survival. When evaluating response to chemotherapy in recurrent cervical cancer, location of metastasis and effect on survival must be considered. PMID- 2920358 TI - The importance of tamoxifen to a cisplatin-containing regimen in the treatment of metastatic melanoma. AB - The combination of dacarbazine (DTIC, 220 mg/m2) and cisplatin (DDP, 25 mg/m2) IV daily for 3 days every 3 weeks, carmustine (BCNU, 150 mg/m2) IV every 6 weeks, and tamoxifen (TAM, 10 mg orally twice daily) produced a 50% objective response rate in patients with metastatic melanoma. Associated with this treatment, there was a high incidence of deep venous thrombosis (DVT) and pulmonary embolism (PE). In an effort to reduce this toxicity, this regimen minus TAM was studied, and the results are reported. Twenty of twenty patients are evaluable for response and toxicity. There was one complete response (CR) lasting 5+ months and one partial response (PR) lasting 4+ months for an overall response rate of 10% (95% confidence limits, 1.23% to 31.70%). Two patients exhibited a mixed response and three patients developed disease stabilization lasting 4 to 10 months. Toxicity was similar to the original study except that no patients developed DVT or PE. This statistically significant (Fisher's exact test [two-tail] P = 0.008) decrease in the response rate by comparison with that achieved with the TAM containing regimen may signal an essential role of TAM in this regimen. TAM may be acting in synergy with cisplatin through its calcium channel-blocking properties. TAM should be included as described in the initial reports, and the patients should be carefully observed for vascular complications. PMID- 2920359 TI - Acquired protein C deficiency in patients with breast cancer receiving cyclophosphamide, methotrexate, and 5-fluorouracil. AB - Recent reports have documented an increase of thrombotic complications in patients with carcinoma of the breast receiving chemotherapy regimens containing cyclophosphamide, methotrexate, and 5-fluorouracil. The authors studied blood from nine such patients screening for abnormalities that might predispose to thrombosis or indicate that the coagulation cascade had been activated. Six of the patients were in the adjuvant setting, and three had metastatic disease. Samples were collected from each patient before, during, and after completion of the chemotherapy in question. In each patient a statistically significant decline in functional protein C activity (P = 0.001) was demonstrated at midtherapy. In seven of nine patients functional protein C level normalized after the cessation of therapy. No other positive results were found. The authors conclude that the combination of cyclophosphamide, methotrexate, and 5-fluorouracil, when administered to patients with a diagnosis of carcinoma of the breast, causes a reversible decline in the activity of protein C. PMID- 2920360 TI - Late regrowth of pituitary adenomas after irradiation and/or surgery. Hazard function analysis. AB - A retrospective analysis was performed on all patients with pituitary adenomas treated at the Radiation Oncology Center, Mallinckrodt Institute of Radiology, St. Louis, Missouri. Of 210 patients treated from April 1954 through December 1982, 70 were treated with radiotherapy alone (RT), 121 received immediate postoperative RT (2 to 6 weeks), and 19 received RT following surgical failure. The mean follow-up time from the date of diagnosis for those patients alive at the time of last follow-up was 13.0 years (range, 3.0 to 30.0 years). Actuarial progression-free survival was analyzed up to 30 years. The 10-, 20-, and 30-year progression-free survival was 80.5%, 73.5%, and 73.5% for those patients treated with irradiation alone and 92.8%, 71.2%, and 44.0% for those treated with immediate postoperative irradiation. The median time to first failure from initial diagnosis by original treatment was 3.8 years for surgery alone, 4.2 years for RT only, and 10.2 years for surgery plus postoperative RT. Analysis for risk of recurrence per 5-year interval was performed using a hazard function analysis. The risk of recurrence after radiotherapy alone was greatest during the first 5-year interval after treatment and decreased to zero by 20 years. However, the risk of recurrence after primary surgery and postoperative radiotherapy revealed an increasing risk for recurrence up to 30 years after treatment. The concept of "cure" for pituitary adenomas requires extended follow-up. PMID- 2920361 TI - Detection of squamous cell carcinoma antigen in normal squamous epithelia and in squamous cell carcinomas of the uterine cervix. AB - Squamous cell carcinoma (SCC) antigen is a subfraction of tumor antigen TA-4 isolated from a cervical squamous cell carcinoma. The specificity of SCC antigen and the factors influencing its release into serum were evaluated. Antigen concentrations were measured in 157 tissue extracts and in 188 sera of patients with nonmalignant or malignant gynecologic diseases. A commercial radioimmunoassay based on polyclonal antibodies (Abbott Laboratories, North Chicago) was used. Cytosol concentrations were significantly higher (P less than 0.005) in normal squamous epithelia (means = 6040 ng/mg cell protein [CP]) and in squamous cell carcinomas (means = 2483 ng/mg CP) of the exocervix than those in normal columnar epithelia and in adenocarcinomas of the endocervix, endometrium, ovary, and breast (means = 1-508 ng/mg CP). Despite the high antigen concentrations in normal squamous epithelia, elevated serum levels (greater than 2.5 ng/ml) were almost exclusively found in patients with cervical squamous cell carcinomas. The sensitivity of SCC antigen as a marker for primary carcinomas was 61%, increasing from 29% in Stage I to 89% in Stage IV. The positivity rate was higher in women with well-differentiated (78%) and moderately differentiated carcinomas (67%) than in those with poorly differentiated tumors (38%). The results show that SCC antigen is not tumor specific. The release into serum is independent of local tissue content, but is apparently influenced by the infiltrative growth, the mass, and the degree of histologic differentiation of the tumor. PMID- 2920362 TI - Effect of yttrium-90-labeled anti-carcinoembryonic antigen monoclonal antibody on the morphology and phenotype of human tumors grown as peritoneal carcinomatosis in athymic mice. AB - Grossly visible peritoneal carcinomatosis resembling that seen in man was produced in athymic mice 7 days after intraperitoneal injection of 8 x 10(5) cells of the carcinoembryonic antigen (CEA)-producing human colon carcinoma cell line LS174T. The mice received intraperitoneal injections of 40 to 160 microCi of yttrium-90 (90Y)-labeled anti-CEA monoclonal antibody (MAb). When the mice were killed 12 days after injection, a significant inhibition of tumor growth, ranging from 40% to 95%, was observed in the treated animals when compared to the growth of tumors in the untreated animals (P less than 0.001). No mortality secondary to the therapy was seen. The bone marrow was depleted significantly at the higher doses of labeled MAb, but total recovery was observed 4 weeks after treatment. Histologically, the treated tumors showed extensive radiation effects early in the posttherapy period and massive necrosis at later times. Minute foci of viable tumor remained in the periphery. New tumor outgrowths with histologic features similar to those in the untreated controls began to appear 3 weeks after therapy. The CEA expression of the treated tumors was similar to that of the untreated controls during the early posttreatment period, diminishing progressively as the tumors became necrotic. Newly grown tumor nodules in the treated animals lacked significant CEA expression both initially and at later times. Our studies suggest that therapy with 90Y-anti-CEA MAb therapy results in selection of tumor clones lacking CEA, and that a single large dose of 90Y-MAb should be more effective than multiple fractions of smaller doses. PMID- 2920363 TI - Experimental model for locally recurring mammary tumors. Development, morphology, karyotype, growth kinetics, and experimental metastatic potential. AB - A rat model was established for evaluating the biology of locally recurring mammary tumors after surgical resection of the primary tumor. Eight distinct cell lines were independently derived from primary tumors and local recurrences after surgical removal of 13762NF rat mammary adenocarcinoma clone MTF7(T20). In vivo tumor doubling times between the "parental" MTF7(T20) cell line, primary tumor derived cell lines sc1 and sc3, and the local recurrence (LR) sublines varied after the inoculation of 10(6) tumor cells into the mammary fat pad of female Fischer 344 rats. Doubling times were shorter for LR3, and LR4, LR5, and LR6 than their primaries sc3 and MTF7(T20), respectively, and longer for LR1 and LR1a than their primary tumor sc1. The LR sublines varied considerably for their experimental metastatic potentials. Both increases and decreases in metastatic potential were seen compared to MTF7(T20), sc1, and sc3. Karyotype analysis by G banding revealed the presence in the LR sublines of several marker chromosomes, previously identified in MTF7 at tissue cultures 11 and 35. Two new chromosome markers were identified: M54, shared by MTF7(T20), sc1, LR4, LR5 and LR6, and M55, shared by MTF7(T20), sc1, LR1, sc3, LR3, LR4, and LR6. These data indicate that local tumor regrowth after surgical excision of the primary tumor in this model most likely selects the growth of tumor cell subpopulations already present within the primary tumor. Differences in growth kinetics, karyotype, and metastatic potential between the parental MTF7(T20), primary tumors sc1 and sc3, and their LR sublines may reflect in vivo influences on the phenotypic diversity generated during the development of local mammary tumor recurrences after surgical treatment of the primary tumor. PMID- 2920364 TI - Mammary fibromatosis. A benign spindle-cell tumor with significant risk for local recurrence. AB - Twenty-two patients with fibromatosis of the breast were studied to define the clinical and pathologic features of this uncommon stromal tumor. All were female patients, 14 to 80 years (median, 25). Bilateral lesions were synchronous in three and asynchronous in one case. One tumor grew near a saline breast implant, one followed trauma, and one arose at the site of excision of a fibroadenoma a year earlier. No patient had Gardner's syndrome. Two patients had contralateral carcinoma and one was previously treated for non-Hodgkin's lymphoma. Two lesions were subareolar. Size ranged from 1 to 10 cm (average, 3 cm). Microscopically, some of the fibrocollagenous proliferations were keloidal. Others were more cellular with rare mitoses (less than 1/10 high-power field). Focal lymphoid infiltrates in about 50% of cases were mainly peripheral. Twenty were treated first by excision and two had mastectomy with residual tumor found in one breast. Six patients (27%) had recurrences after 2 to 72 months (average, 30 mo) including one bilateral recurrence. Recurrences in four cases were treated by reexcision, one had no treatment, and one mastectomy was performed for a 4-cm recurrence. Although histologically benign, mammary fibromatosis recurs locally and rarely when recurrent requires radical surgery. It should not be mistaken for an inflammatory condition. Wide local excision is recommended for initial therapy. PMID- 2920365 TI - Prognostic value of quantitative pathologic features and DNA content in individual patients with stage I endometrial adenocarcinoma. AB - The prognostic value of clinical features, qualitative and quantitative pathologic characteristics and steroid receptor incidence was evaluated in 50 patients with Stage I endometrial adenocarcinoma. It turned out that many of these features were prognostically important. Estrogen receptor content was not significantly associated with prognosis in our material, but patients with progesterone receptor positive lesions had a better survival than those in which the tumors were progesterone receptor negative. Multivariate analysis also clarified that only three features in combination had independent significance: mean shortest nuclear axis, DNA index, and depth of myometrial invasion (in sequence of decreasing importance). The prognostic rule consisting of these features overshadowed the value of all other features investigated. The overriding prognostic value of this highly reproducible rule was clear from the complete separation of 27 survivors and six nonsurvivors in the learning set of 33 patients. In an independent test set, all three nonsurvivors and 13 of the 14 survivors were correctly classified, thus confirming the accuracy and reliability of the developed rule to predict the outcome of future patients with Stage I endometrial adenocarcinoma. PMID- 2920366 TI - Thrombotic microangiopathy in three patients with cured lymphoma. AB - Thrombotic microangiopathy (TM) occurred 14 to 27 months after last chemotherapy in two patients with diffuse large cell lymphoma and in one patient with Hodgkin's disease. Death from TM occurred in two patients who had no evidence of lymphoma at postmortem examination, and the lone survivor's disease is in complete clinical remission. All three patients had prominent arthritis. Occurrence of TM in non-Hodgkin's lymphoma has not previously been reported: its cause is uncertain; it may be to a late sequela of successful lymphoma chemotherapy. PMID- 2920367 TI - Prospective evaluation of diagnostic accuracy of gastrofiberscopic biopsy in diagnosis of gastric cancer. AB - The accuracy of gastrofiberscopic biopsy in diagnosis of gastric malignancies has been evaluated by studying operative and postmorten findings and clinical follow up data in linkages at Osaka Cancer Registry, Japan, after an average of 7.7 years. Satisfactory data were obtained in follow-ups of all 1331 patients examined. There were only 31 (3.7%) false-negative diagnoses of malignancy among 858 patients diagnosed as having benign lesions, and only three (0.6%) false positive diagnoses among 473 patients diagnosed as having malignant tumors. The false-negative diagnoses were most frequent in cases of elevated types of early cancer, advanced cancer of type 4 and leiomyosarcoma, or in cases located in the posterior wall and in the antrum. The three benign lesions that were diagnosed as malignant by biopsy were all associated with active ulceration, indicating that care is necessary in taking biopsy specimens of ulcerated lesions. From these findings the sensitivity and specificity of the gastrofiberscopic biopsy method for detection of gastric malignancies were calculated to be 93.8% and 99.6%, respectively, and the overall accuracy for all the patients was 97.4%. These results reconfirm that gastrofiberscopic biopsy is very useful for diagnosis of gastric malignancies. PMID- 2920368 TI - Selection criteria for local excision with or without adjuvant radiation therapy for rectal cancer. AB - As an alternative to radical surgery, local excision with or without adjuvant pelvic radiation therapy has been used in selected patients with rectal cancer. To determine which clinical and pathologic features can predict the presence of positive lymph nodes (LN+), a retrospective review of 168 patients who underwent potentially curative surgery for rectosigmoid and rectal cancer was performed. By univariate analysis, tumor penetration, grade, and histology were significant predictive features. This was confirmed by logistic regression analysis. The incidence of LN+ increased with increasing tumor penetration (T1, 0%; T2, 28%; T3, 36%; T4, 53%; P = 0.04), grade of adenocarcinoma (well-differentiated, 0%; moderately differentiated, 30%; poorly differentiated, 50%; P = 0.07, [borderline significance]), and the presence of any colloid histology (pure adenocarcinoma, 30%; total colloid, 52%; P = 0.04). Using 2 X 2 contingency tables, the presence of blood vessel invasion (BVI), lymphatic vessel invasion (LVI), vascular invasion (VI), total colloid histology, and high grade further increased the incidence of LN+ with increasing tumor penetration. Regardless of tumor size, grade, histology, BVI, LVI, or VI, none of the nine patients with Stage T1 tumors or the seven with well-differentiated adenocarcinomas had LN+. For this group, local excision alone is recommended. The incidence of LN+ was greater than or equal to 19% in all other categories. For this group of patients, if there is no evidence of gross tumor in the pelvis, then a local excision plus adjuvant pelvic radiation may be an alternative to radical surgery. PMID- 2920369 TI - Cutaneous malignant melanoma. II. The natural history and prognostic factors influencing the development of stage II disease. AB - The survival history of 259 patients with Stage I cutaneous malignant melanoma who were at risk for developing regional nodal metastases (Stage II) were studied. Eighty-seven of 377 Stage I patients (23%) developed regional nodal metastases (Stage IIB) with 40% 5-year survival. Fifty patients had regional nodal metastases at presentation, with or without a known primary (Stages IIA or IIC, respectively), with a 42% 5-year survival. A step-down multivariate analysis using the Cox regression model revealed four risk factors as being highly significant for predicting a more favorable survival outcome: (1) thinner Breslow thickness (P = 0.0001), (2) pathologic Stage I disease (P = 0.004), (3) no clinical ulceration (P = 0.0004), and (4) being a woman younger than 50 years of age (P = 0.029). These results are discussed in reference to other series. PMID- 2920370 TI - Special communication. The Cooperative Human Tissue Network. AB - This report is to make the general scientific community aware of availability of human tissues through this network. During the short period of its existence, this network has developed useful procedures for distributing human tumor tissue in a rapid, scientifically useful, cost-effective manner to investigators to whom this tissue would not otherwise be available. The growth in the number of specimens being distributed matches the previous experience of each of the member institutions in internal distribution activities. It is expected that the availability of tissue will lead to new research initiatives and grant applications. This Network has been established as a model which can in the future be expanded to meet the needs of the scientific community at large. The National Cancer Institute encourages investigators engaging in cancer research who have need of human tissues to submit their requests to the Cooperative Human Tissue Network. PMID- 2920371 TI - Effect of dietary linoleic acid level on lodgement, proliferation and survival of mammary tumor metastases. AB - High levels of dietary linoleic acid (18:2) have been shown to increase the spontaneous metastasis of line 4526 mouse mammary tumors. In this report, the influence of 18:2 on specific events of tumor metastasis, namely, lodgement, proliferation and survival, were studied using spontaneous and experimental metastasis assays with line 4526 cells. A significantly greater number of radiolabeled tumor cells lodged in the lungs of mice fed 4, 8 and 12% 18:2 when compared with mice fed lower levels of 18:2. The effect of dietary 18:2 appeared to be on the host tissue (lungs) and not the tumor cells. Lodgement of tumor cells first cultured in serum of mice fed 18:2 then injected into mice fed 1% 18:2 was not affected. There were no significant differences in the percentage of [3H]thymidine labeled metastatic cells from lungs of mice fed different levels of 18:2. However, the number of surface lung nodules that appeared in mice 21 days after injection of unlabeled line 4526 cells increased in mice fed 8 and 12% 18:2 compared with those fed lower levels of 18:2. Thus, dietary 18:2 may increase metastasis by influencing the lodgement, implantation and survival but not proliferation of line 4526 mouse mammary tumor cells. PMID- 2920372 TI - Characterization of two monoclonal antibodies that recognize high molecular weight colon antigens. AB - Two monoclonal antibodies, M32-1 (Ig-G1,k) and M39-2 (IgM,k), were prepared against high molecular weight (greater than 650 kDa) cytosol antigens (HMW-CA) of a human adenocarcinoma of the colon (GW-39). These monoclonal antibodies appeared to bind to determinants on two distinct high molecular weight colon antigens. One was shown by gel filtration to be a 650 kDa glycoprotein (gp650) containing at least one 300 kDa antigenic subunit (gp300). The other antigen eluted from a S 300 Sephacryl column at a molecular size of 600 kDa (gp600) and was resistant to dissociation by detergents, salts and chaotropic agents. The differential sensitivity of these two high molecular weight glycoproteins to treatment with trypsin, chondroitinase ABC, HNO2, endoglycosidase H and 2-mercaptoethanol suggest that monoclonal antibodies M39-1 and M39-2 react with distinct antigenic determinants located on two separate, high molecular weight, colon antigens. Since these antigens are only detected in extracts prepared from normal mucosa, well-differentiated tumors or margins of well-differentiated tumors, their expression appears to be related to a well-differentiated cell phenotype. PMID- 2920373 TI - Modulation of murine melanoma growth by naloxone. AB - The present study was undertaken to determine the effect of the opioid receptor antagonist, naloxone, on the growth of B16 melanoma, a murine tumor known to possess opioid receptors. Naloxone inhibited the growth of B16 melanoma in vitro when monolayer cultures were continuously exposed to concentrations of greater than or equal to 0.25 mg/ml. Tumor cell proliferation as measured by [3H]thymidine ([3H]Tdr) incorporation is reduced by a continuous 48-h treatment with greater than or equal to 0.025 mg/ml but slightly enhanced by a 6-h treatment. The administration of naloxone to mice caused a transient inhibition of subcutaneous local tumor growth at doses of 0.1, 1 and 10 mg/kg daily. At a dose of 10 mg/kg daily, naloxone caused a slight reduction in the number of pulmonary metastases following the intravenous inoculation of tumor cells. The mechanism by which naloxone inhibits tumor growth in vivo is not clear, but factors other than direct cytotoxicity may also be involved. The results further support the role of the endogenous opioid system in the modulation of tumor growth. PMID- 2920374 TI - The high sensitivity of cells transformed by E1A gene of adenovirus type 12 to diacylglycerol-mediated cell killing. AB - Viability of rat 3Y1 fibroblasts transformed by adenovirus type 12 (Ad12) was markedly impaired by the administration of dilinoleoylglycerol (DLG) to the culture medium. To identify the gene(s) of Ad12 responsible for the high sensitivity to DLG, we established several transformed sublines of 3Y1 induced by the viral E1A gene or by the mutants of Ad12 which have mutations in the E1A region. All of the transformed sublines of 3Y1 expressing either the 12S or the 13S message from the E1A region were highly sensitive to the cytotoxicity of DLG. We propose that the high sensitivity of Ad12-transformed cells to the DLG mediated cytotoxicity is attributable to the common function of E1A-12S and E1A 13S mRNA products. PMID- 2920375 TI - Inducibility of glutathione S-transferases in hamsters. AB - The effects of 3-methylcholanthrene (3-MC), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), phenobarbital, trans-stilbene oxide (TSO), pregnenolone-16 alpha carbonitrile (PCN), dexamethasone, ethanol, isoniazid and butylated hydroxyanisole (BHA) on hepatic glutathione S-transferase (GST) activities toward six substrates were determined in hamsters. TCDD and 3-MC, which are comparatively poor inducers of GSTs in rats, were most effective in enhancing GST activities in hamster liver. In contrast, TSO, BHA and phenobarbital, which are very effective inducers of hepatic GSTs in rats and mice, were ineffective or poor inducers of GSTs in hamster liver. While dexamethasone increased some GST activities, treatments with PCN, ethanol and isoniazid were without effect. The findings indicate that not only the control activity but also the inducibility of hepatic GSTs are different in hamsters from those in other species. PMID- 2920377 TI - Skin tumors: experimental and clinical aspects. PMID- 2920376 TI - Lack of initiating activity of the peroxisome proliferator ciprofibrate in two stage hepatocarcinogenesis. AB - The peroxisome proliferator ciprofibrate was examined for its ability to initiate hepatocarcinogenesis in rats. Ciprofibrate was fed in the diet at levels of 0%, 0.01% and 0.025% for 2 weeks in order to induce steady-state peroxisome proliferation. Rats were then subjected to partial hepatectomy and then maintained for 6 months on a basal diet or one containing 0.05% phenobarbital. Ciprofibrate treatment did not increase the number or volume of altered hepatic foci (putative preneoplastic lesions). However, ciprofibrate treatment increased liver weights in a dose-dependent manner in rats which did not receive phenobarbital. It is concluded that ciprofibrate-induced peroxisome proliferation is not sufficient to induce initiation, but that a permanent change is produced which results in an increased liver weight. PMID- 2920378 TI - Comparative study of the composition of primary and secondary dentine. AB - There is considerable variation in the composition of primary and secondary dentine. In general, secondary deposits, regardless of type, contain less calcium, phosphorous, and collagenous matrix per unit volume when compared to primary dentine. Fluoride levels show the reverse tendency. These observations suggest a more open, porotic structure for secondary deposits. PMID- 2920379 TI - Acidogenesis by oral streptococci at different pH values. AB - Streptococcus mutans is known to be one of the most cariogenic oral microorganisms. Recently, organisms classified as S. mutans have been shown to be genotypically heterogeneous and to form at least six separate species. In this study, differences in acid production between the mutans streptococci and Streptococcus sanguis were investigated at pH values from 5.0 to 7.0. While all of the species investigated were able to produce acids, Streptococcus sobrinus was found to be significantly more acidogenic than the others. S. sobrinus was capable of sustained acid production at pH levels below 6.0, while acid production by other species ceased or was strongly inhibited. These results indicate that S. sobrinus deserves more attention as a potentially cariogenic microorganism. PMID- 2920380 TI - Interactions of zinc with fluoride on growth, glycolysis and survival of Streptococcus mutans GS-5. AB - Effects of zinc and/or fluoride on growth, glycolysis and survival of Streptococcus mutans GS-5 were examined in vitro. Zinc inhibited growth and glycolysis, and enhanced the antimetabolic activity of fluoride. Zinc alone had little effect on cell survival. During cell growth without pH control a protection from cell death was mediated by fluoride, which appeared to be caused by a higher final pH in the culture medium. When cell death was observed under controlled pH conditions in a lactate-acetate buffer at pH 6.5, 5.0 or 4.0, fluoride was bactericidal only at pH 4.0. However, the combination of zinc plus fluoride was strongly bactericidal at all pH values that were tested. PMID- 2920381 TI - Effect of systemic fluoride on rat molar morphology. Stereophotogrammetric analysis. AB - Female Sprague-Dawley rats were divided into three groups. All three groups were given the same solid diet (with 1.6 ppm F). Group I was given deionized water, group II drank water with 5 ppm fluoride added, and group III had 50 ppm fluoride added. All females were mated with the same male. The pups were sacrificed at 28 days, and the mandibles were removed and cleaned. Three-dimensional representations of the occlusal surfaces of the 1st and 2nd mandibular molars were reproduced via computer-digitized images using stereophotogrammetry. Fissure depths and widths were measured, and 'volumes' of the fissures were computed. The fissure widths, depths, and volumes were compared statistically using unpaired t tests between groups (p less than 0.05). There were significant differences in fissure depth between groups I and II and between groups I and III. For fissure volumes, significant differences were found between groups I and III. The width of the fissure and the overall tooth size were not significantly different between fluoride-treated groups. Standardization showed a reproducibility to within +/- 40 mm with the stereophotogrammetric method. PMID- 2920382 TI - Dentine caries in vivo. Combined scanning electron microscopic and microradiographic investigation. AB - Dentine subjected to an in vivo demineralization challenge by plaque looses substantial amounts of mineral and is expected to change its ultrastructure. Results are presented of a combined microradiography and scanning electron microscopy (SEM) study on in vivo demineralized human dentine. The tissue was first demineralized in vivo under plaque for 3 weeks and subsequently analyzed by microradiography and SEM. In 6 participants dentine was positioned in a full prosthesis just under M2 in such a way that the outer surface of the tissue was 1.5 mm lower than the surface of the prosthesis; plaque accumulation takes place in the recessed area. A special technique allows SEM observations (at a given distance from the outer surface) on broken thin sections of demineralized dentine with a mineral content determined by microradiography. The results show that the ultrastructure of the dentine changes during severe demineralization. The main ultrastructural features are, however, still largely intact, even if half of the mineral originally present has been lost. In dentine with a mineral content of about 25 vol%, the dentinal tubules are enlarged by about 30%. In vivo demineralized dentine looses mineral in substantial amounts both from intertubular and from peritubular regions. PMID- 2920383 TI - Effects of Parafilm and cheese chewing on human dental plaque pH and metabolism. AB - The effects of chewing Parafilm and cheese following sucrose rinsing on human dental plaque pH and plaque fluid organic and amino acid concentrations were investigated. Immediate increases in plaque pH were observed following chewing with concomitant decreases in lactate and acetate concentrations and increases in the concentration of formate and many amino acids. Chewing with cheese when compared with Parafilm resulted in significantly higher (p less than 0.05) plaque fluid concentrations of most amino acids, although significant decreases (p less than 0.05) in phosphate, succinate, and acetate concentrations were observed. However, no significant difference in the levels of formate, lactate, and propionate were found between the two chewing treatments. PMID- 2920384 TI - Caries-related microbiological findings in a group of teenagers and their parents. AB - The levels of salivary Streptococcus mutans and lactobacilli and caries experience were studied in 113 teenagers and 163 adults. The study population consisted of 82 mother-child and 73 father-child pairs. The number of decayed, missing, and filled tooth surfaces (DMFS) was eightfold higher in adults than in teenagers (56.4 +/- 22.8 vs. 7.3 +/- 6.7). The percentage distribution of the level of salivary S. mutans and lactobacilli was approximately the same in both groups. The mean number of DMFS increased with increasing levels of salivary S. mutans and lactobacilli, the correlation being highly significant both in teenagers and adults. There was a significant correlation of the DMFS indices in the mother-child pairs (r = 0.364), but the correlation was not significant in the father-child pairs (r = 0.138). The salivary level of S. mutans was higher in the children of mothers with high DMFS values compared to the children of mothers with low DMFS values. PMID- 2920385 TI - Protection by F, I, Sr, and combinations against fermentation attack by Streptococcus sobrinus artificial plaque on bovine enamel. AB - Labial surfaces of 64 bovine incisors (8 teeth/treatment) were subjected to 1-min treatment with (1) 500 ppm Sr, (2) 0.5% I2 plus 1% KI solution, (3) F varnish treatment (Duraphat) for 24 h, or (4) combined treatments. The treated teeth were incubated under an artificial Streptococcus sobrinus plaque for 10 days. The 'oral fluid' with maleate buffer (pH 5.8) partially saturated with Ca3(PO4)2 and with or without 3.3% sucrose or sucrose plus 25 ppm F, was replaced by a mixture containing thioglycolate broth and the buffer for 4 h daily. This was done in an attempt to maintain the viability of the plaque as it was not renewed. Analysis of the Ca and inorganic P in the fluid phase taken after the 1st and the 10th day of incubation indicated that complete protection was obtained with F varnishing plus 25 ppm F in the fluid, with added sucrose. The Sr plus F treatment was more protective than F or Sr alone. The iodine treatment was slightly protective when combined with F varnishing. The results of the enamel surface and subsurface F and Sr as well as measurements of surface microhardness also indicated the highest protective effect with the double-F treatment and a marked protection provided by the Sr plus F treatment. The efficacy of the double-F treatment was partly explained by the prevention of a fall in 'plaque' pH and partly by the release of bacterial inorganic P in the extracellular fluid. The present caries model is versatile in quantification of changes in numerous parameters (14 parameters measured) involved in the caries-like process and its inhibition. PMID- 2920386 TI - Cardiac catheterization: who's doing the teaching? PMID- 2920387 TI - Hemodynamic abnormalities during coronary angiography: comparison of Hypaque-76, Hexabrix, and Omnipaque-350. AB - The hemodynamic effects induced by coronary angiography in dogs with low osmolar ionic dimer Hexabrix (HB) and nonionic Omnipaque-350 (OM) were compared to the standard ionic contrast medium, Hypaque-76 (H76), both in the normal heart and in one with simulated severe cardiac disease. Left coronary angiography was performed in 12 "normal" closed-chest dogs with 10-cc injections of H76, HB, and OM in a randomized, blinded fashion. The maximal change in the left ventricular (LV) systolic pressure (SP), mean aortic pressure (MAP), left ventricular end diastolic pressure (LVEDP), and LV dp/dt were recorded. The LVSP and MAP fell 30 +/- 3 mm Hg and 26 +/- 4 mm Hg with H76, 22 +/- 2 mm Hg and 19 +/- 2 mm Hg with HB, and 7 +/- 1.5 mm Hg and 5 +/- 1 mm Hg with OM (P less than .001). The LVEDP increased 4.8 +/- 0.5 mm Hg with H76, 3 +/- 0.5 mm Hg with HB, but only 0.2 mm Hg with OM (P less than .001). The LV dp/dt decreased 392 +/- 63 mm Hg/sec with H76 and 235 +/- 21 mm Hg/sec with HB, but increased 411 +/- 50 mm Hg with OM (P less than .001). In eight additional open-chest dogs, left coronary angiography was performed 1 hr after occlusion of the proximal LAD coronary artery and in the presence of a critical circumflex coronary artery (CX) stenosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2920388 TI - Angiographic coronary morphology in postinfarction angina. AB - To investigate the pathophysiologic relevance of angiographically irregular coronary stenoses in postinfarction angina (PIA), we analyzed the clinical course and coronary angiograms of 73 patients studied within 30 days of infarction. Coronary lesions were classified as smooth or irregular. Thirty-six patients had PIA (Group 1) and 37 had an uncomplicated course (Group 2). Irregular lesion(s) in patent infarct-related arteries were found in 77% of Group 1 vs. 24% of Group 2 patients (P less than 0.005). Irregular lesion(s) in any coronary artery were found in 58% of Group 1 versus 19% of Group 2 patients (P less than 0.002). Other univariate predictors of PIA included older age, hypertension, angina before myocardial infarct, lower peak creatine kinase, three-vessel disease, and higher modified Gensini score. Multivariate analysis ranked lesion irregularity as the strongest predictor of PIA. Our data suggests that ruptured atherosclerotic plaques may be important in the pathogenesis of PIA. It is possible that lesion irregularity is associated with an active process and/or a residual thrombus, which may be responsible for postinfarction angina. PMID- 2920389 TI - Dual connection of the left anterior descending coronary artery to the left and right coronary arteries. AB - Origin of the left anterior descending coronary artery from the right coronary artery is a well-described but rare congenital coronary anomaly. In this report, we describe two cases in which the mid left anterior descending coronary artery is connected to the right coronary artery through an intraseptal connecting vessel, while the proximal left anterior descending coronary artery originates normally from the left main coronary artery. This previously unreported pattern suggests partial persistence of the peritruncal ring, which occurs during normal embryologic development of the coronary circulation. Even though it is classically described as an epicardial structure, the vascular pattern in our cases suggests that the peritruncal ring may have an intramural segment in some individuals. PMID- 2920390 TI - Inadvertent Swan-Ganz catheter placement in the left pericardiophrenic vein. AB - Placement of flow-directed Swan-Ganz catheters without fluoroscopic guidance occasionally results in placement in positions other than the pulmonary artery. In the case presented, the inadvertent placement of such a catheter into the left pericardiophrenic vein was probably facilitated by distortion of the right heart and systemic venous anatomy. PMID- 2920391 TI - Echocardiographic findings in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC). AB - Although a variety of cardiac abnormalities have been described in AIDS patients, it is unclear whether these are incidental findings or they presage clinically important heart disease. Also, because AIDS-related complex (ARC) is, in general, a milder form of AIDS, we wondered if echocardiographic abnormalities would differ in kind or in frequency, when compared with AIDS. To answer these questions, we studied the echocardiographic findings and the demographic features of 15 patients with AIDS and 24 patients with ARC. The ARC group had abnormalities in the same proportion as in our AIDS group, except for echocardiographic mitral valve prolapse. The MVP, however, did not appear to be due to intrinsic valvular disease. Rather, echocardiographic MVP was associated with low body weight (P = .02) but not with the cardiac signs or symptoms of MVP. Four AIDS patients had LV dysfunction. Of the echocardiographic variables, only a wide EPSS was significantly correlated with survival, as it is in other populations. We conclude that although echocardiographic abnormalities are common in AIDS and ARC patients, most of these abnormalities lack clinical significance. PMID- 2920392 TI - Safety and convenience of a mechanical injector pump for coronary angiography. AB - Coronary angiography and left ventriculography was performed in 5,887 consecutive patients over a 5-year period using a mechanical injector pump activated by a foot switch. Five coronary dissections occurred, four of the right coronary artery and one of the left internal mammary artery, which had been grafted to the left anterior descending artery. One patient had angina following an air embolus; there were no significant intramyocardial injections of contrast agent. The pressure generated in the catheter by hand injection of contrast agent was compared with that generated by the injector pump. Contrast agent was injected through a 7F Judkins Right 4 and an 8F Sones catheter by hand at slow, medium, and fast rates by hand and by the injector pump at 2,3, and 4 ml/sec; maximum pressure generated was recorded. Although the pressures generated through a Sones catheter were similar using both methods, pressures with hand injection were much more variable. The pressures generated with hand injection through a Judkins catheter were lower than those with pump injection, but again the pressures showed much greater variability with hand injection. The pump was found to be safe, reliable, predictable, and convenient when used for coronary angiography with Sones and Judkins catheters. It eliminates the need for a trained assistant during the procedure of coronary angiography. PMID- 2920393 TI - Accurate determination of the transaortic valve gradient using simultaneous left ventricular and femoral artery pressures. AB - Accurate determination of the transaortic valve gradient has required two catheters, one in the left ventricle and one in the ascending aorta. We now report a new technique for measurement of the transaortic valve gradient from the simultaneous left ventricular (LV) and femoral artery (FA) pressure tracings. This technique was compared with the "true" gradient obtained by measurement of the simultaneous LV and central aortic pressures, and is accurate (R = 0.999) and relatively simple. Other approaches used to determine the mean transaortic valve gradient were less accurate: simultaneous LV-FA (R = 0.991); aligned LV-FA (R = 0.974); averaged simultaneous and aligned LV-FA (R = 0.981); and nonsimultaneous LV-aorta pullback (R = 0.953). Thus, this new technique provides an accurate transaortic valve gradient without requiring the use of two central catheters. PMID- 2920394 TI - The potential risk of thrombosis during coronary angiography using nonionic contrast media. AB - The influence of contrast media on coagulation has an important association with thromboembolic complication during coronary angiography. In this study, whole blood was methodically mixed with nonionic contrast medium, Iohexol (IOH), conventional ionic contrast medium, Hypaque-76 (H76), and low osmolar ionic dimer Hexabrix (HB) in vitro. The thrombotic propensity of contrast agents can be evaluated by measuring the clot formation of the mixtures. The experiments were repeated with whole blood after systemic heparinization. In the in vitro study, 5 ml of canine (N = 10) and 3 ml of human (N = 11) whole blood was incubated for 30 min in glass tubes with equal volumes of IOH, H76, HB, and 0.9% NaCl before heparinization. Clot formation with IOH and 0.9% NaCl were seen both in dogs (4.0 +/- 0.7 gm and 5.6 +/- 0.8 gm) and in patients (1.4 +/- 0.9 gm and 2.9 +/- 1.3 gm), whereas no clot was seen with H76 or XB. Following heparinization, no clot was visualized in any mixture of whole blood with contrast media or 0.9% NaCl. Similar results were observed in the catheter-syringe system with canine blood (N = 11) mixed with the contrast agents. Blood clots found in 15 min and 30 min of IOH were 0.07 +/- 0.08 gm and 0.44 +/- 0.20 gm (P less than 0.01) and of NaCl were 0.29 +/- 0.37 gm and 0.69 +/- 0.38 gm (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2920395 TI - In situ analysis of antibody-forming cells from the BALB/c CRIc idiotype family: idiotopic heterogeneity among clustered cells. AB - Immunocytochemical staining methods were applied toward defining the in situ expansion of the BALB/c mouse antibody-forming cells (AFC) that express the CRIc idiotype (id) family associated with the antibody response against the p azophenylarsonate (Ar) hapten. CRIc+ AFC dominated the early primary anti-Ar response but represented a decreased fraction of the anti-Ar AFC during secondary responses. Two subsets of the CRIc family, CRIc1 and CRIc2, differed in their relative expression, with CRIc1 more pronounced during primary responses and CRIc2 better expanded in secondary responses. Idiotopic differences among AFC in very close proximity suggested convergent migration among B cells having similar but not identical V regions or possibly V region mutations among clonally derived cells. The approach also allowed in situ idiotypic analysis of polyclonally activated B AFC. PMID- 2920396 TI - In vitro regeneration of activated rat peritoneal mast cells cocultured with 3T3 fibroblasts. AB - Rat peritoneal mast cells (MC) cocultured with 3T3 fibroblasts (MC/3T3) were activated by compound 48/80 to release most of their histamine content (approximately 90%). These activated MC could be kept viable in vitro for as long as 2 weeks, during which their regeneration had been followed. As early as 3-4 hr following activation, the MC started reacquiring their resting morphology. In 1-2 weeks they were more densely granulated grossly resembling nonactivated, control MC. Reactivation of MC/3T3 with compound 48/80 on Day 7 or 14 of culture resulted in a percentage histamine release which was similar to that of Day 0, and to control MC/3T3, indicating that these activated MC were functionally responsive. Activated MC/3T3 could partially resynthesize histamine during the 14 days of culture following activation. On Day 7 their histamine content was approximately 23% and on Day 14 approximately 40% of the initial amount they had on Day 0, prior to activation. Thus, MC/3T3 activated by compound 48/80 in vitro can regenerate by resuming their initial morphology, becoming responsive to a subsequent reactivation and resynthesizing histamine. PMID- 2920397 TI - Partial characterization of a low-molecular-weight, macrophage-derived inhibitor of DNA synthesis: a possible immunoregulatory molecule. AB - It has been previously reported that tumor-associated macrophages isolated after combination therapy contained an activity that inhibited thymocyte proliferation in the IL-1 comitogenic assay. The present report shows that this macrophage derived inhibitory factor (MDIF) inhibits DNA synthesis in diverse adherent and nonadherent cells in vitro. The elution pattern seen after chromatography using Bio-Gel P10 or Sephadex G-25 columns indicated a molecular size of 3-6.5 kDa. However, full activity was retained when MDIF was passed through an Amicon filtration membrane having a cut off of 500 Da. It was also seen that other molecules less than 500 Da, such as thymidine, thimerosal, and PGE2, each of which was also shown to be growth inhibitory, eluted in a size range similar to that of MDIF after chromatographic separation. Ion exchange chromatography confirmed that MDIF was distinct from thymidine, and a radioimmunoassay indicated that PGE2 was not responsible for MDIF activity. Little or no inhibitory activity could be detected in macrophages isolated from progressing tumors or from tumors excised after cyclophosphamide treatment of tumor bearers. Given that this inhibitory activity was associated with macrophages derived from tumors induced to regress by combination therapy, the possibility is discussed that MDIF may play an important role during the regulation of immune reactions at the tumor site. PMID- 2920398 TI - [Specific and nonspecific indicators of activation of influenza viruses before an epidemic caused by influenza viruses subtype A/H3N2 and type B in Czechoslovakia in 1986]. AB - The authors submit an aetiological and epidemiological analysis of the influenza epidemic which occurred in the CSR between the 4th and 14th week of 1986 and was caused by the influenza virus subtype A/H3N2/ and type B. The epidemic affected a total of 27.1% of the population, in the age group of 0-5 years 63.7%, in the age group 6-14 years 52.7% and in the age group above 15 years 17.1%. In the course of the epidemic 77,458 cases of pneumonia and bronchitis were reported and 1,412 deaths with the diagnosis influenza, bronchitis, pneumonia and chronic affection of the lungs. The authors analyze also specific indicators of the activation of influenza viruses and reach the conclusion that serological evidence of the circulation of influenza viruses in the population was detected already in the third quarter of 1985, the first isolations were made six weeks before the influenza epidemic. Activation of the influenza viruses is indicated already during the pre-epidemic period by some non-specific indicators which include the rising number of patients with acute respiratory affections in surgeries and the rising number of children absent from nurseries and nursery schools on account of these diseases. The most sensitive non-specific indicator is the rising number of patients with respiratory diseases in surgeries of the First aid medical service. PMID- 2920399 TI - [Comparison of 2 methods for determining antibodies to collagen: the ELISA test and passive hemagglutination]. AB - For the determination of antibodies against collagen in different rheumatic diseases the authors elaborated two serological techniques. It was particularly the passive haemagglutination, which proved to be little sensitive and insufficiently reproducible. Therefore, for the determination of antibodies against collagen the authors introduced the ELISA method as one of the varieties of enzyme immunoanalysis, giving more precise results. Both methods were compared and it has become apparent that the ELISA method is more reliable and more suitable for the determination of antibodies against collagen. PMID- 2920400 TI - [The importance of the microprecipitation reaction in agar in the diagnosis of toxoplasmosis]. AB - The authors examined 56 pigs by an isolation experiment for Toxoplasma gondii and simultaneously by the Sabin-Feldman reaction, microprecipitation reaction in agar (MPA), quantitative microprecipitation reaction in agar (MPAK), reaction with complement-fixing and indirect haemagglutination reaction with toxoplasma antigen. In nine pigs with positive isolation finding, the Sabin-Feldman reaction and quantitative microprecipitation reaction in agar was positive in eight cases. In cases of negative Sabin-Feldman reaction, the quantitative microprecipitation reaction was always negative. The quantitative microprecipitation reaction in agar is therefore a suitable indicator of the success of isolation experiments. For a simplicity of the test it is suitable for immunological diagnostics of toxoplasmosis in pigs in common practice. PMID- 2920401 TI - [A standard code for naming microbes]. AB - The author suggests a code for communication and processing of data which involves the formation of code names, in particular of microorganisms. These code is reached after agreement, made compulsory and then strictly respected. The principle for the formation of the code is relative comprehensibility, simplicity and orientation on a given area of application. The generation of the code is made by a computer. PMID- 2920402 TI - Kinetic study of the Jaffe reaction for quantifying creatinine in serum: 2. Evaluation of buffered reagent and comparison of different data-processing options. AB - Here we describe the evaluation of several data-processing options for the kinetic determination of creatinine by use of the Jaffe reaction. Data-processing options evaluated include initial-rate, two-point fixed-time, rate at t = k-1, and multipoint curve-fitting predictive methods. We evaluated these options for a buffered formulation of the Jaffe reagent and studied the effects of potential interferents, including glucose, acetoacetate, bilirubin, and albumin, on each option. To reduce effects of bilirubin, we evaluated the inclusion of a preoxidation step with ferricyanide. All the data-processing options gave good precision and linearity between the measurement objective and creatinine concentration. However, differences between slopes of calibration plots in aqueous and serum matrices ranged from a high of +60% for the two-point, fixed time method to a low of -11% for the curve-fitting, predictive method. Standard additions of creatinine to sera were quantified reliably (yielding 96% to 102% of target values) by the predictive method and less reliably (62% to 102%) by the other methods. We conclude that the predictive method has the potential to yield the most reliable results for creatinine. PMID- 2920403 TI - Short-term and long-term variability of indices related to nutritional status. I: Ca, Cu, Fe, Mg, and Zn. AB - Five free-living women (ages 28-38 y) and five women (ages 23-44 y) residing in a metabolic unit and eating a constant diet were assessed for variation in indices related to mineral nutrition. Blood was sampled once a month for five months, once a week for five weeks, and once a day for five days to assess analytical and biological variability. Analytical variability was determined by using concurrently run duplicate control samples prepared from plasma or serum pools. Of the measured indices, serum ferritin varied most, with intra-individual variance of 4.72% to 18.0%. Much of this variance may have been because of changes in iron status or in the analytical technique used. Intra-individual month-to-month variance for other indices ranged from 17% for superoxide dismutase (EC 1.15.1.1) to 1.5% for calcium. Correction for long-term analytical variation indicated that most of the variance was associated with the biological component. The higher biological variabilities of some indices, including ferritin or superoxide dismutase, need to be considered when nutritional status is being evaluated or when serial observations are made over a protracted period in clinical studies or trials. PMID- 2920404 TI - Rapid, reliable in vivo assays of human phosphate metabolites by nuclear magnetic resonance. AB - This accurate, reliable, and fast method of assaying absolute concentrations of phosphate metabolites noninvasively in living tissue, including that of humans, combines 31P nuclear magnetic resonance (NMR) spectroscopy and 1H NMR imaging. The images are used to measure the areas of metabolite-bearing tissue in selected sections through the subject, and 31P spectra are acquired from the same section, together with a concentration reference located on the periphery. Metabolite concentrations are calculated from the ratios of areas and integrated signal intensities. Apparatus and protocol are designed to eliminate corrections due to magnetic field nonuniformities and NMR relaxation times. Mean (and SD) concentrations of adenosine triphosphate (ATP), phosphocreatine, and inorganic phosphate (Pi) measured in the brains of 15 normal adult human volunteers with a 1.5-T NMR system were 3.03 (0.49), 5.18 (0.89), and 1.5 (0.7) mmol per liter of wet tissue, respectively. Acquisition times of only a few minutes should facilitate metabolic studies of patients with disorders in limbs and brain, particularly those affecting entire organs. PMID- 2920405 TI - Lactate dehydrogenase isoenzyme pattern in sera of patients with malignant diseases. AB - Total lactate dehydrogenase (LDH; EC 1.1.1.27) activity and the percentage distribution of LDH isoenzymes were determined in 127 patients with malignant diseases. A shift in the isoenzyme patterns was observed toward the M-type, with an increase in the percentage of LDH-4 and LDH-5 isoenzymes and a slight increase in total LDH activity of all patients. Serum samples from 68 of the patients contained an abnormal isoenzyme of LDH, "LDH-1 ex," that, on agarose gel electrophoresis at pH 8.6, migrated between albumin and LDH-1 isoenzyme. Chemotherapy, radiotherapy, or surgical removal of the tumor was accompanied by disappearance of this abnormal isoenzyme. The heat stability of LDH-1 ex isoenzyme appears to be similar to that of LDH-1 but greater than that of the other LDH isoenzymes. Statistical analysis of these data demonstrated a significant correlation between malignancy and the appearance of LDH-1 ex isoenzyme (P less than 0.001). In contrast, the relationship between LDH-1 ex isoenzyme and metastasis or anatomical location of the malignancy is not statistically important (P less than 0.1). PMID- 2920406 TI - Differences between capillary and venous blood-alcohol concentrations as a function of time after drinking, with emphasis on sampling variations in left vs right arm. AB - Twelve healthy men drank 0.8 g of ethanol per kilogram of body weight during 30 min after an overnight (10 h) fast. At nine exactly timed intervals (30-390 min after the start of drinking), blood was sampled through indwelling catheters in cubital veins on the left and right arms. Immediately thereafter, capillary blood was sampled from fingertips on the left and right hands. The blood ethanol concentration (BAC) was determined by headspace gas chromatography. The SD for alcohol determinations in venous blood, including the left vs right arm sampling variation, was 30 mg/L (range 8.3-83 mg/L), whereas for capillary blood the SD was 35 mg/L (range 11-60 mg/L). This difference much exceeded the purely analytical errors: SD = 2.67 mg/L for venous blood and 14.2 mg/L for fingertip blood. During the first 60 min after the subjects started to drink, capillary BAC exceeded venous BAC, the mean difference at 30 min being 136 mg/L (range 36-216 mg/L). In the postabsorptive state later than 60 min after drinking, venous BAC exceeded capillary BAC [mean difference 58 mg/L (range 0.0-170 mg/L]), the values for venous and capillary BAC crossing 37 min (range 6-77 min) after the end of drinking. Apparently, the source of blood analyzed, venous or capillary, must be considered in clinical pharmacokinetic studies of ethanol. PMID- 2920407 TI - Standardization of a commercial (Boehringer Mannheim diagnostics) enzymic method for cholesterol. AB - The Laboratory Standardization Panel of the National Cholesterol Education Program recommends that cholesterol method accuracy ideally be within 3% of the true value determined by the Abell-Kendall Reference Method, a component of the National Reference System for Cholesterol. As one of the Abell-Kendall network laboratories established to facilitate cholesterol standardization, the approach we recommend for determining accuracy involves a comparison analysis on patients' specimens by the method in question and by the Abell-Kendall method. Use of fresh specimens precludes matrix interactions that may influence enzymic measurement. Using this approach, we assessed an enzymic method for cholesterol with two instruments (Boehringer Mannheim/Hitachi 717 and 737), with BMD reagent, controls, and calibrator. Fresh and frozen sera were analyzed with both instruments over three days. The Abell-Kendall method was used at the Northwest Lipid Research Center on frozen aliquots of the same sera. Both instruments demonstrated good agreement with the Reference Method, as determined by linear regression; overall bias averaged less than -2% for the Hitachi 717 and -1% for the Hitachi 737 at 2000 mg/L--i.e., within the accuracy recommendation. We observed a difference in bias for fresh and frozen specimens; with the Hitachi 717, fresh specimens exhibited -3% bias at 2000 mg/L, but there was virtually no bias of determinations of frozen specimens. PMID- 2920408 TI - Changes in creatine kinase activity in the course of acute myocardial infarction. AB - Peak activity of creatine kinase (CK; EC 2.7.3.2) and its decline were determined in 380 patients with acute myocardial infarction (AMI) whose CK values had peaked after admission to the hospital. During hospitalization, 26 patients either died (14 patients) or experienced nonfatal re-infarction (12 patients). In 22 of these 26 patients CK activity decreased by less than 50% within 48 h after the peak value was measured. In all patients who did not die or develop re-infarction, CK activity decreased by greater than 50% during the 48 h after the peak. Evidently the rate of decline of CK (i.e., whether more than or less than 50%) from its peak value during the 48 h after AMI may be helpful in assessing which patients are at high risk for developing re-infarction or dying. PMID- 2920409 TI - Chromatofocusing and isoelectric focusing in immobilized pH gradients compared for characterization of human hemoglobin variants. AB - We compared the performance of two highly resolving methods, chromatofocusing (CRF) and isoelectric focusing in immobilized pH gradients (IPGF), for the separation of human hemoglobin variants. Lysates containing 13 different hemoglobins, including variants of clinical and geographical importance, and four electrophoretically "silent" variants (Hb Brockton, Hb Cheverly, Hb Koln, and Hb Waco) were analyzed. Both techniques showed a good intrarun precision (CV = 0.87% for CRF, 0.27% for IPGF) and high and similar resolving power (0.010 pH units, with the pH gradients used in this work). The use of an ultranarrow IPGF range (pH 7.15-7.35; pH gradient = 0.019 pH/cm) allowed the resolution between Hb Brockton, Hb Koln, and Hb A. In some cases (Hb D-Los Angeles, Hb F, Hb Waco), the variants were separated from Hb A in different orders, depending on which technique was used, probably because of the different analytical principles of the two methods. As a second-level test, both procedures are informative for characterization of human hemoglobin variants. PMID- 2920410 TI - Diagnosis of acute myocardial infarction from two measurements of creatine kinase isoenzyme MB with use of nonparametric probability estimation. AB - By using bivariate probability estimation for the diagnosis of acute myocardial infarction (AMI) we show how to overcome the difficulties encountered for patients whose clinical presentation is atypical and those encountered when multiple isoenzyme determinations are treated by univariate methods. We use the values for creatine kinase isoenzyme MB measured at the time of admission and 12 h later to estimate the Bayes factors in favor of AMI. The Bayes factors are compiled into a table that the clinician can use to estimate the posterior probability that a patient has AMI. The table of Bayes factors is based on data for a sample of 802 non-AMI patients and 180 AMI patients. Further to validate the method, we randomly chose 200 of the non-AMI and 50 of the AMI patients as an evaluation sample, then used the remaining 602 non-AMI and 130 AMI patients to recompute the Bayes factors. These Bayes factors were used to find the probability of AMI for each of the 250 patients in the evaluation sample. The method resulted in only one false positive and no false negatives. For the misclassified patient the measurements at admission and 12 h later were 1 and 11 U/L; the posterior odds were 15 to 1 in favor of AMI, but in fact the patient was non-AMI. PMID- 2920411 TI - A self-consistent set of reference values for 23 clinical chemical analytes. AB - Heparinized plasma of 528 blood donors was subjected to the 23 most frequently ordered chemical and enzymatic tests. The central fraction of the distribution of all results for each test was estimated. Out of the 528 donors a reference population has been selected. Because of the lack of other criteria, the result for any test of a blood donor was selected as a value belonging to the reference population if the results for the other 22 analytes of this particular donor lay within their own central fraction. On this basis an iterative procedure for the selection was programmed, considering the interaction between tests. The procedure was stopped when the reference limits for all 23 tests were converging. Fractions from 0.90 to 0.98 were applied to results for men and women donors separately. The elimination procedure and the criteria to select the best fitted fraction are discussed. The derived reference intervals are designated a "self consistent set of reference values." PMID- 2920412 TI - Automated determination of drugs in serum by column-switching high-performance liquid chromatography. IV. Separation of tricyclic and tetracyclic antidepressants and their metabolites. AB - We describe automated column-switching high-performance liquid chromatography for determining nine tricyclic and tetracyclic antidepressants (TCAs) and their metabolites in human serum. TSKgel ODS-80TM and TSKprecolumn PW (Tosoh Co., Tokyo) are used in the analytical column and the precolumn, respectively. A 200 microL serum sample is directly injected onto the precolumn. After washing the serum proteins from the precolumn with potassium phosphate buffer, the precolumn connection is switched to introduce the retained substances onto the analytical column. The drugs are then eluted within 30 min with an acetonitrile/potassium phosphate buffer mixture containing sodium 1-heptanesulfonate. The analytical recoveries (95-104%), reproducibilities (within-run CV less than 3%), and detection limits (10 micrograms/L) indicate that this HPLC system is suited for therapeutic drug monitoring. Correlations were good between the TCA concentrations in serum and administered dose (r = 0.713, n = 41), and between 10 hydroxynortriptyline and nortriptyline in serum (r = 0.691, n = 24). PMID- 2920413 TI - Screening for microalbuminuria by use of a rapid, low-cost colorimetric assay. AB - We evaluated the pyrogallol red-molybdate(IV) method for quantification of urinary protein as a screening procedure for microalbuminuria by determining the assay's sensitivity and specificity at different concentrations of urinary albumin as measured by a comparison laser-nephelometric immunoassay. The pyrogallol red-molybdate(IV) method has sensitivity and specificity similar to that for other semiquantitative assays, but it is less expensive and sample throughput can be high if microtiter plate techniques are used. PMID- 2920414 TI - Erythrocyte sedimentation rate and C-reactive protein compared in the elderly. AB - The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) concentrations were studied in 101 elderly individuals (mean age 72 y) to determine their utility as diagnostic aids in subjects with underlying infection/inflammation. Whereas ESR and CRP were both significantly increased in patients with infection or inflammation, or both, analysis of variance indicated that those subjects still alive six months later had significantly lower ESR values. Analysis of sensitivity, specificity, and positive predictive values indicated that neither test satisfactorily discriminated between patients with and those without ongoing active or chronic disease. Receiver-operating characteristic curve analysis confirmed the low true-positive/false-positive ratios of both ESR and CRP. In the elderly, neither CRP nor ESR has distinct advantages over the other, and both tests evidently have limited utility. PMID- 2920415 TI - Liquid-chromatographic assay of urinary porphobilinogen. AB - This is a rapid (10 min per sample), highly sensitive procedure for quantifying urinary porphobilinogen (PBG). Interfering substances are removed by selectively adsorbing PBG onto an ion-exchange resin. After PBG is eluted with 0.5 mol/L formic acid, Ehrlich's reagent is added to produce the chromophore, which is then injected into a liquid chromatograph equipped with a diode-array detector. PBG is separated by a linear gradient (10% to 100%) of methanol in 10 mmol/L phosphate buffer, pH 3.0. Absorbance is monitored at 555 nm. Assay response varies linearly with PBG concentration over the range 0-110 mumol/L (0-25 mg/L). As little as 1.5 mumol/L (0.3 mg/L) can be detected. In prepared urine samples with known PBG concentrations, the within-run coefficient of variation (CV) ranged from 1.7% to 3.2%, the day-to-day CV from 3.5% to 6.1%. PBG concentrations in 24-h urine collected from 25 healthy subjects were all below the detection limit of the assay (less than 1.5 mumol/L). We used the new assay to measure PBG concentrations in the urine of two patients with latent porphyria. This method is more sensitive than spectrophotometric techniques currently used for measuring urinary PBG. PMID- 2920416 TI - Automated determination of urinary Na+, K+, chloride, inorganic phosphate, urea, and creatinine without sample dilution, with the "RA-XT". AB - We describe how concentrations of chloride, urea, inorganic phosphate, and creatinine in urine can be measured directly, without manual sample dilution, in a discrete analyzer (the Technicon "RA-XT"). These methods were accurate for concentrations of chloride up to 280 mmol/L, urea up to 500 mmol/L, inorganic phosphate up to 50 mmol/L, and creatinine up to 30 mmol/L. CVs are less than 3% nd results correlate well with those obtained by continuous-flow analysis (SMA II). All these reagents are stable at room temperature for three weeks. Analyses are easy to perform and infrequent calibration is required. PMID- 2920417 TI - Interference of coumarin therapy with the "Heptest" owing to declining prothrombin concentrations. AB - The Heptest kit (Haemachem, Inc., St. Louis, MO) for quantifying heparin in plasma is based on heparin-mediated inhibition of factor Xa, resulting in prolongation of clotting time. In 19 of 55 plasma samples obtained from 32 patients concurrently receiving coumarin and heparin, Heptest results exceeded true heparin values by more than 0.2 int. unit/mL; four samples showed a deviation exceeding 0.4 int. unit/mL. We show here that these deviations are caused by coumarin-induced decreases of plasma prothrombin. This problem can be circumvented by adding purified prothrombin or normal plasma to the assay mixture. PMID- 2920418 TI - Effect of hematocrit and added heparin on ionized calcium in capillary blood samples from neonates. AB - Sampling of capillary blood for determination of ionized calcium (Ca2+) in neonates requires that extra heparin be added to prevent clotting in the sampling tube and (or) in the Ca2+ analyzer. Because the additive dissolves in the plasma compartment, different hematocrit (erythrocyte volume fraction, EVF) values may cause different results for Ca2+. To study the effect of EVF and heparin additive, we repeatedly removed plasma, thereby increasing the EVF. These samples with different EVF's were aspirated into commercial capillary tubes containing heparin and, according to our routine procedure, an additional 10 microL (approximately 0.9 int. unit) of sodium heparin. We found a negative bias of 0.05 0.09 mmol/L in Ca2+, depending on the EVF. Adding saline instead of heparin gave the same effect, indicating that this bias was entirely due to dilution. We suggest compensating for this by adding 0.09 mmol/L to the actual value for ionized calcium when EVF exceeds 70%. The increase in Ca2+ in neonates on days 1 to 5 postpartum is physiological and not an effect of change in EVF. PMID- 2920419 TI - Time-resolved fluorescence immunoassay system especially suited for research applications. PMID- 2920420 TI - New method for determining bound and ionized calcium in serum. PMID- 2920421 TI - Two commercial test kits for CK-MM isoforms evaluated for early recognition of acute myocardial infarction. PMID- 2920422 TI - HPLC determination of hemoglobin A1C in the presence of the fast hemoglobin I Philadelphia. PMID- 2920423 TI - An unusual band that binds hemoglobin after ultracentrifugation of hemolyzed plasma for lipoprotein separation. PMID- 2920424 TI - Effect of storage conditions on saliva thiocyanate concentration. PMID- 2920425 TI - Fructosamine assay modified for the estimation of glycated hemoglobin. PMID- 2920426 TI - Emetine identified in urine by HPLC, with fluorescence and ultraviolet/diode array detection, in a patient with cardiomyopathy. AB - A 15-year-old girl with a four-month history of cardiac failure from undetermined cause was admitted to the hospital with weakness, fatigue, and weight loss. During her hospitalization she was found to have abused diet aids, laxatives, and cathartics. Although an electrocardiogram revealed nonspecific T-wave abnormalities and laboratory studies showed supranormal enzyme test results for creatine kinase and lactate dehydrogenase, no definite explanation of the cardiomyopathy was forthcoming. Ipecac abuse leading to cardiomyopathy was suspected early in the hospitalization. HPLC analysis of a urine sample showed emetine, a principle component of ipecac, the presence of which was later confirmed by more-specific HPLC analysis with photodiode array detection. PMID- 2920427 TI - The new International Temperature Scale of 1990 (ITS-90). AB - A new international temperature scale, the ITS-90, will replace the International Practical Temperature Scale of 1968 (amended edition of 1975), IPTS-68(75), on 1 January 1990. Temperatures on the ITS-90 will agree more closely with thermodynamic temperatures; therefore, the ITS-90 represents a substantial improvement over the IPTS-68(75). Fortunately for the clinical laboratory community, the change in the scale will be at most only 0.05 degrees C or less in the range from 0 to 60 degrees C, but corrections in primary calibrations should be made so that the calibrations are based on the ITS-90. PMID- 2920428 TI - Determination of 4,4'-methylenebis(2-chloroaniline) in urine. PMID- 2920429 TI - Serum magnesium as affected by drugs. PMID- 2920430 TI - Strategy for diagnosis of monoclonal gammopathies in serum. PMID- 2920431 TI - Differentiating between sensitivity and limit of detection. PMID- 2920432 TI - Quality control of glucose monitors outside the clinical laboratory: use of commercial nonhuman erythrocyte preparations supplemented with additional glucose. PMID- 2920433 TI - Differences between alkaline phosphatase activities in serum and lyophilized controls in AMP buffer explained. PMID- 2920434 TI - Direct determination of free thyroxin in undiluted serum by equilibrium dialysis/radioimmunoassay. PMID- 2920435 TI - Modified method of analysis for metadrenaline in urine. PMID- 2920436 TI - Incorporation of butylated hydroxytoluene in the mobile phase increases sensitivity in carotenoid chromatography. PMID- 2920437 TI - Salivary melatonin estimation in assessment of pineal-gland function. PMID- 2920438 TI - Disturbance of the determination of hemoglobin concentration in patients with high leukocyte counts. PMID- 2920439 TI - Specific determination of plasma dexamethasone by HPLC and RIA--application to standard dexamethasone suppression test in psychiatric patients. AB - Three radioimmunoassays (RIA), with or without preparative HPLC, were applied to the monitoring of plasma dexamethasone (DXM) levels during standard dexamethasone suppression test (DST) in psychiatric patients. Due to the robotic ease of the fully automated HPLC process, precision of the chromatographic assay was equivalent to that of the direct assays, but prepurification improved both sensitivity and specificity. These improvements allowed the elucidation of the following features: (1) half (36) of the patients (68) displayed infranormal DXM levels (less than or equal to 0.40 ng/ml) whatever the cortisol response; (2) 22% (15) patients (68) with DXM levels in the low control range showed a strong inhibition of cortisol suppression. These observations raise some doubts on the validity of the DST test and introduce the following questions. (1) What is the dependence of cortisol suppression upon DXM absorption and catabolism? (2) Does plasma DXM measurement several hours after its physiological action still reflect its effect on the hypothalamo-hypophyseal axis? (3) What is the reliability of DXM direct assays when measuring low DXM levels in the presence of high cortisol? PMID- 2920441 TI - Complement activation after prolonged exercise. AB - The effects of a 2.5-h running test on the concentrations of the complement cleavage products C3a, C4a and C5a in plasma were examined in eight healthy young males. In all participants the C3a and C4a values were raised during (1 h after the start) and immediately after exercise. C4a was also raised 1 and 3 h after the race. These results provide evidence for complement activation after prolonged exercise. PMID- 2920440 TI - Association between increased concentrations of free thyroxine and unsaturated free fatty acids in non-thyroidal illnesses: role of albumin. AB - We measured the concentrations of non-esterified free fatty acids and free and total thyroid hormones in serum from patients with various non-thyroidal illnesses (NTI) and chronic renal failure (CRF). The total concentration of free fatty acids was measured enzymatically and the eight most abundant fractions were determined by gas-liquid chromatography. The concentration of total free fatty acids was significantly increased in the NTI group as compared with controls (p less than 0.01); the concentrations of oleic, linoleic and linolenic acid were increased more than those of the other fractions. In NTI the serum-free thyroxine (FT4) concentration was increased (p less than 0.01) and the free triiodothyronine (FT3) concentration was decreased (p less than 0.001); these concentrations were measured by equilibrium dialysis. There was a significant correlation between the levels of total free fatty acids and FT4 in the NTI (n = 43) group (r = 0.45, p less than 0.01), and also between the levels of linoleic acid and FT4 (r = 0.35, p less than 0.05). The serum albumin concentration was decreased in the NTI group, and when free fatty acid to albumin molar ratios were calculated stronger correlations with FT4 were observed (total free fatty acids: r = 0.55; p less than 0.001; oleic acid: r = 0.30, p less than 0.05; linoleic acid: r = 0.46, p less than 0.01; linolenic acid: r = 0.35, p less than 0.05). There was no correlation between FT4 and unsaturated FFA concentrations in CRF patients, who had normal mean FT4 and total FFA levels. These results support the hypothesis that unsaturated fatty acids are involved in the increase of serum FT4 in NTI, especially when albumin levels are low. PMID- 2920442 TI - Urinary excretion of 2,3-butanediol and acetoin by babies on a special care unit. AB - 2,3-Butanediol was detected by capillary gas chromatography in 45 urine samples from 20 babies on a special care unit, 17 of whom were premature. The meso form of the diol predominated and in 21 samples was the only diastereoisomer present. Acetoin was found in 20 of the samples. It was never detected in the absence of 2,3-butanediol. 2,3-Butanediol was not detectable in more than trace amounts in urine from 66 other babies on the unit. The most likely origin of these compounds was from bacterial fermentation of pyruvate in the gut. Their presence may be explained by abnormal gut colonisation with acetoin-producing microorganisms, an abundant supply of nutrient lactose in the colon and increased intestinal permeability. It is further evidence of the magnitude of intestinal carbohydrate fermentation in preterm babies. 2,3-Butanediol could prove a useful biochemical marker for abnormal colonisation of neonates on special care units. PMID- 2920444 TI - The determination of plasma oxalate concentrations using an enzyme/bioluminescent assay. 2. Co-immobilisation of bioluminescent enzymes and studies of in vitro oxalogenesis. AB - An inexpensive, continuous flow assay for the determination of oxalate in plasma is described. The assay is based on the bioluminescent determination of NADH, a product of the degradation of oxalate by oxalate decarboxylase and formate dehydrogenase, using bioluminescent enzymes immobilized on cyanogen bromide activated sepharose. The detection limit of the assay is 0.8 mumol/l. Intra-batch CV values of 5.2 and 3.8% were obtained at oxalate concentrations of 18 and 60 mumol/l. Recovery of added oxalate averaged 100.7%. Plasma oxalate ranged from less than 0.8 to 2 mumol/l in 14 healthy subjects, and from 6 to 134 mumol/l in 125 patients with renal disease treated by continuous ambulatory peritoneal dialysis. Ascorbic and dehydroascorbic acid did not directly interfere in the assay. In vitro oxalogenesis was observed in blood from 12 healthy subjects, but only after samples had stood at room temperature for more than 6 h. No significant oxalate generation occurred in blood from 24 patients with impaired renal function, even after standing at room temperature for 24 h. Oxalate generation was inhibited by the addition of oxalate to plasma, but the addition of urea and creatinine was without effect. PMID- 2920443 TI - Validation of the Friedewald formula for the measurement of low density lipoprotein cholesterol in insulin-dependent diabetes mellitus. AB - The Friedewald formula has been widely used in the estimation of the serum LDL cholesterol concentration in diabetic patients. In patients with insulin dependent diabetes we have compared the serum LDL cholesterol concentrations obtained when VLDL was isolated in the preparative ultracentrifuge and its cholesterol content directly determined with those when the 'Friedewald Formula' assumption that there is a fixed ratio between total serum triglycerides and VLDL cholesterol was used in the calculation of the LDL cholesterol value. Both methods gave similar results which were closely correlated (r = 0.98) with a slope of 0.98 on linear regression analysis for patients with serum triglycerides of less than 2.5 mmol/l. The inclusion of a small number of hypertriglyceridaemic patients (14%) had virtually no impact on these findings. PMID- 2920445 TI - Effect of fish oil supplementation on erythrocyte lipid pattern, malondialdehyde production and glutathione-peroxidase activity in psoriasis. AB - Erythrocytes from psoriatic patients have a significant increase in polyunsaturated fatty acids (p less than 0.001) especially in arachidonic acid (p less than 0.001). Glutathione peroxidase activity, in both erythrocytes and platelets, was stimulated when compared with normal cells (p less than 0.001, less than 0.02, respectively) and the production of malondialdehyde was also increased in psoriasis (p less than 0.01). The level of plasma selenium was significantly reduced (52.80 vs 72.49 ng/ml; p less than 0.001). alpha-Tocopherol and retinol were both normal in plasma of psoriatics. After two months of fish oil supplementation, the erythrocyte lipid pattern was changed, eicosapentaenoic and dochesaenoic acids substituting the arachidonate in the membrane. A reduction in malondialdehyde (p less than 0.01), a prolongation of bleeding time (p less than 0.05) and a further stimulation of glutathione-peroxidase (p less than 0.001) in both erythrocytes and platelets was also found. PMID- 2920446 TI - Human plasma contains low molecular weight factors which stimulate active sodium transport in erythrocytes. AB - The aim of this study was to establish whether differences in sodium efflux rate constants (ke) in human erythrocytes occur when artificial media are compared with plasma. Using a 22Na tracer method, a mean total ke of 0.49 +/- 0.10 h-1 and significantly (p less than 0.05) lower ke values in Hanks' solution (0.43 +/- 0.08 h-1) and Basic Salt Solution (0.37 +/- 0.07 h-1) were observed. Exhaustive dialysis of plasma against Hanks' solution over a membrane with relative molecular mass cut-off of 1000 Da resulted in a decrease of the plasma total ke value to that measured in Hanks' solution. After equilibrium dialysis of plasma against Hanks' solution a decrease of total ke was found in plasma and an increase of the ke in Hanks' solution was measured. The data suggest the presence of an excess of dialyzable, active sodium transport stimulating plasma factor(s) with relative molecular mass below 1000 Da. PMID- 2920447 TI - Racial effect on serum creatine-kinase: implications for estimation of heterozygosity risks for females at-risk for Duchenne dystrophy. PMID- 2920448 TI - Determination of tellurium in biological fluids by means of electrothermal vaporization-inductively coupled plasma-mass spectrometry (ETV-ICP-MS). PMID- 2920450 TI - Serum and ascitic fluid concentrations of apolipoproteins A and B in alcoholic cirrhosis patients. PMID- 2920449 TI - Carboxyl terminal glycine extended progastrin (gastrin-G) in human gastric mucosa and gastrinomas. PMID- 2920451 TI - GdMRI--good value at 150 DM a vial? PMID- 2920452 TI - Tympanosclerosis: a scanning electron microscopic study. AB - Twelve specimens of tympanosclerosis were examined. Six were immediately fixed in 3% glutaraldehyde and 6 were obtained from the departmental collection of specimens in wax blocks which had previously been examined by light microscopy. Seven specimens were demineralized. The material was examined macroscopically, by light microscopy and by scanning electron microscopy to a magnification of x25,000. The microstructure of tympanosclerosis is an irregular three-dimensional collagen lattice, enclosing distinct, spherical, mineralized aggregates, housed in lacunar-like spaces. This lattice is continuous with the plaque surface which is an envelope, probably of proteinaceous material. The spherical calcified aggregates were absent from the demineralized specimens. There was no structural difference in the scanning electron microscopic appearances of specimens processed conventionally in 3% glutaraldehyde and those previously embedded in wax. PMID- 2920453 TI - No peak-peak tympanometric conversion following surgery for otitis media with effusion in relation to airway size: a new treatment strategy? AB - This study was performed to examine the relationship between the pre-operative radiographic palatal airway and no peak-peak tympanometric conversion 1 yr following adenoidectomy, adenotonsillectomy or no pharyngeal surgery performed for otitis media with effusion. A relationship between the airway in children with otitis media with effusion and matched controls is described and this is used to analyse tympanometric change in 3 airway size groups. No peak-peak conversion was significantly greater following adenoidectomy or adenotonsillectomy compared with no pharyngeal surgery in those with small airways and tonsillectomy conferred no additional benefit. Adenoidectomy with or without tonsillectomy is probably best avoided in children with large radiographic palatal airway measurements when planning surgical treatment for established disease, although this may ultimately be related to age at operation. PMID- 2920454 TI - Evaluation of a computer interview system for use with neuro-otology patients. AB - The effectiveness, feasibility and credibility of a computer assessment package was evaluated in a group of 60 neuro-otological outpatients. The computer system was compared with a standard questionnaire and used to elicit basic neuro otological information prior to clinical interview. The majority of patients (81%) preferred computer assessment. There were no differences in attitude or difficulties between diagnostic groups. Older patients had more difficulties and took longer than younger patients. The computer system was also more efficient than the form from an information handling and administrative point of view. PMID- 2920455 TI - Antroscopy: a comparison between the sublabial (canine fossa) and intranasal (inferior meatus) approaches as an out-patient procedure. AB - We present a prospective randomized study comparing two approaches for out patient antroscopy. The traditional inferior meatus route was seen to be associated with a higher incidence of discomfort and significant complications. An alternative route via the canine fossa provided easier access, better patient tolerance and improved visualization of the antral contents. It was associated with a lower incidence of immediate complications, although there were a number of delayed symptoms, all of which were mild and transient. The canine fossa approach under local anaesthesia offers an effective and more acceptable alternative for antroscopy as an out-patient procedure. PMID- 2920456 TI - Hypaque and steroids in the treatment of sudden sensorineural hearing loss. AB - While the origins of sudden sensorineural hearing loss remain unproven and treatment empirical, the most appropriate therapy remains a matter of controversy. In this paper we have analysed the current forms of treatment, i.e. diatrizoate meglumine, steroids and a vasodilator. The results suggest that although several related factors were shown to indicate a good prognosis regardless of the therapy, none of the currently available regimens produces consistently better results than the spontaneous recovery rate of 65% reported by Mattox & Simmons. PMID- 2920457 TI - The location of the upper oesophageal sphincter and its behaviour during bolus propagation--a simultaneous cineradiographic and manometric investigation. AB - By means of simultaneous cineradiographic and manometric examinations using closely positioned microtransducers the maximal pressure of the upper oesophageal sphincter was found at a level 20 mm below the plane of the vocal folds and 6 mm above the level of the cricoid arch. The sum of these 2 distances is in accordance with the distance between the vocal fold level and the lower border of the cricoid arch given in the literature. This implies that the high pressure zone of the upper oesophageal sphincter corresponds to the pars fundiformis of the cricopharyngeus muscle. The lower part of the inferior pharyngeal constrictor and the upper circular muscle fibres of the oesophagus contribute to the sphincter. When the bolus approached the sphincter, the pressure decreased and during bolus passage the pressure was below or well below half of the resting pressure. The pressure profile disclosed no signs of muscular dyscoordination or discontinuity of the upper oesophageal sphincter. PMID- 2920459 TI - Dermatologic therapy II. PMID- 2920458 TI - Magnetic resonance imaging in head and neck cancer. AB - The scans of 120 patients with proven head and neck cancer who underwent magnetic resonance imaging (MRI) at Mt. Vernon hospital were reviewed and, where possible, compared with their clinical, computed tomography (CT) and histological findings. MRI was generally superior to both clinical examination and CT in the detection of cervical lymphadenopathy and in the assessment of primary tumour extent, particularly in the tongue base, nasopharynx and parotid gland. Small intracranial tumour extensions were more readily detected by MRI than CT. MRI was no better than CT in distinguishing between malignant and inflamed tissues and was generally inferior to CT in spatial resolution, patient acceptance and examination cost. PMID- 2920460 TI - Wound repairs. Unusual problems and solutions. AB - This article presents solutions to difficult surgical repair problems. Solutions for the repair of defects in the ear (in this case the ear lobule) and upper lip are discussed. A solution is also provided for an exasperating problem that arises when cheek and neck lifts are done. An aid for the design of cutaneous flaps is shown, and an improvisation that can be used for the closure of wounds near the nose and upper lip is presented. Properly used, this technique can enhance the cosmetic result of wound closures that might otherwise distort the ala nasi or structures near the lip. PMID- 2920461 TI - Tattoos. AB - Tattoo removal is a difficult, risky task that should not be undertaken lightly. Postprocedural scars are inevitable and unavoidable. Salabrasion is often the best removal procedure, if it will work. Also included for discussion are various excision techniques. PMID- 2920462 TI - Treatment of mucoid cysts of fingers and toes by injection of sclerosant. AB - Mucoid cysts of the fingers and toes may be cured by injection of a sclerosant such as sodium tetradecyl sulfate. Easy to perform and inexpensive, this technique appears to be without complications. Most patients are cured after a single injection. Very few need a second or third injection. Relapses are uncommon. PMID- 2920463 TI - Informed consent for chemical peels and dermabrasion. AB - Clinicians have an obligation to make sure that patients are adequately informed and understand, first, the general risks involved in any elective procedure, and, second, whether there are any features in their medical profiles that pose greater risks or pose the possibility of greater benefits than the average patient. Patients must understand the concepts of general risk, the possibility of unpredictable events happening randomly, and their own personal risk of having this happen. The remainder of the article deals with the information regularly provided to patients who show an interest in dermabrasions or chemical peels. PMID- 2920464 TI - Alternative topical therapy. AB - Although there have been revolutionary changes in the management and treatment of dermatologic disorders with topical therapies, these potent remedies do not always work in recalcitrant and intractable cases. When all the "modern" preparations have been exhausted, falling back on some old remedies often proves curative. This article offers a list of 73 alternative topical measures that are often beneficial. PMID- 2920465 TI - Therapeutic potpourri. AB - Many older treatments should not be discarded because of newer modalities. Various dermatologic disorders may be controlled effectively by prescribing these older topical agents. PMID- 2920466 TI - The renal metabolism of pepsinogen A and C in man. AB - Pepsinogen A (PGA) and pepsinogen C (PGC) are almost identical low molecular weight proteins with marked differences in renal handling. PGA is present in large amounts while PGC is almost absent in the urine of healthy subjects. Whether the amount of PGA in the urine represents the total amount of PGA that is extracted, is unknown. We, therefore, assessed the renal metabolism of PGA and PGC by measuring PGA, PGC and creatinine concentrations in the aorta and the right renal vein, and in the urine from patients undergoing elective heart catheterization. The renal extractions of PGA and PGC were not significantly different from the extraction of creatinine: 22%, 18% and 24%, respectively. Sixty-eight percent of PGA and 98% of PGC extracted from the circulation were metabolized by the kidney, and fractional metabolism was closely related to the fractional reabsorption of PGA and PGC from the glomerular filtrate. It is concluded that the kidney metabolizes PGA and PGC. The fractional metabolism of PGA and PGC can be calculated from the fractional reabsorption. Further studies on the renal handling of pepsinogens are warranted as they may provide information on factors affecting renal metabolism of low molecular weight proteins. PMID- 2920467 TI - Adult respiratory distress syndrome following administration of nitroprusside in postpartum acute renal failure. PMID- 2920468 TI - Rapid diagnosis of hemodialysis catheter sepsis. PMID- 2920469 TI - Human recombinant erythropoietin treatment in transfusion dependent anemic patients on maintenance hemodialysis. AB - Six anemic hemodialysis patients dependent on regular blood transfusions and with massive iron overload were treated with recombinant human erythropoietin (r huEPO). The effect on absolute reticulocyte count, hemoglobin and serum ferritin was studied during a twenty-week period. Red-cell volume and red-cell life span were measured with 51Cr-tagged erythrocytes at baseline and after twenty weeks of r-huEPO. Absolute reticulocyte counts and hemoglobin concentration rose markedly (from 55.6 +/- 31.2 to a maximum of 174.9 +/- 31.0 x 10(9)/l at 4 weeks and from 6.8 +/- 0.3 to a maximum of 11.2 +/- 1.3 g/dl at 12 weeks, respectively, p less than 0.001) without any further need for transfusions. Red-cell volumes increased concomitantly (from 58 +/- 4 to 81 +/- 11% of normal, p less than 0.005), in spite of a persistent shortening of red-cell life span (45 +/- 18 and 47 +/- 4 days before and after r-huEPO). Markedly elevated serum ferritin concentrations indicating iron overload decreased slowly from 3,550 +/- 1,615 to 2,721 +/- 1,506 micrograms/l (p less than 0.05). It is concluded that r-huEPO is very effective in treating the anemia of patients maintained on hemodialysis. The favorable effects on hemoglobin and red-cell volumes occur in spite of persistent hemolysis and lead to a slow reduction of iron overload. PMID- 2920470 TI - Long-term prognosis of chronic idiopathic membranous glomerulonephritis. An analysis of 334 cases with particular regard to tubulo-interstitial changes. AB - A retrospective long-term study (average follow-up time 5.2 years) of 334 patients with idiopathic membranous glomerulonephritis (MGN) was carried out with the following results: 1) MGN was found to have a relatively good prognosis when all cases were considered together: 5-year kidney survival rate (KSR) -88%, and 10-year KSR -77%. 2) Univariate survivorship analysis showed the following morphological and clinical parameters to be associated with an increased risk of terminal renal insufficiency or death from renal disease: a) tubulo-interstitial changes; b) glomerular stage III as opposed to stages I and II; c) elevation of serum creatinine concentration at the time of the biopsy; d) arterial hypertension at the time of the biopsy. 3) Multivariate analysis showed that only tubulo-interstitial changes (interstitial fibrosis and/or acute renal failure) found at the time of the biopsy and their clinical correlate, serum creatinine concentration, were significant and therefore of definite prognostic importance. 4) Unsystematic therapy with steroids and/or cytostatic agents does not improve the long-term prognosis of MGN. 5) The cause of disease in the tubulo interstitial system in MGN is discussed. Interstitial fibrosis is considered to develop possibly as a consequence of unresorbed interstitial edema which can develop during an episode of acute renal failure. Coexisting T-cell-mediated disease in the region of the intertubular capillaries is also considered as a possible factor in the development of interstitial fibrosis. PMID- 2920471 TI - Clinical and laboratory features of patients with chronic renal disease at the start of dialysis. AB - We examined clinical and laboratory features retrospectively in 402 patients at the start of chronic hemodialysis in order to define better the "uremic syndrome" in the dialysis era. The information gathered included demographic data, renal diagnoses, uremic symptoms, biochemical values, and prevalences of hypertension (69%), diabetes mellitus (23%) and ischemic heart disease (16%). Unexpected findings were the wide ranges of serum creatinine levels (3.5 to 35 mg/dl) and blood urea nitrogen levels (35 to 345 mg/dl), and the frequency of hyponatremia (27%), hypoalbuminemia (52%), and anion gaps above 25 mg/dl (5%). There were higher hematocrits in males and diabetics, lower serum creatinine levels in females, diabetics and older patients, and lower blood urea nitrogen levels in blacks. The time interval from diagnosis of diabetes mellitus to initiation of dialysis in patients with diabetic nephropathy due to juvenile-onset diabetes mellitus (20.6 +/- 6.8 years) was twice that in adult onset diabetes mellitus (10.3 +/- 8.3 years). PMID- 2920472 TI - Apolipoprotein B turnover in dialysis patients: its relationship to pathogenesis of hyperlipidemia. AB - Exogenously labelled Iodine-125-VLDL (very low density lipoprotein) was given intravenously to twelve dialysis patients and four normal controls. Specific activities of I-125-VLDL apoB (apolipoprotein B) and I-125-IDLapoB (intermediate density lipoprotein apolipoprotein B) were measured for forty-eight hours. Synthesis rates (flux) and fractional catabolic rates (FCRs) of VLDLapoB and IDLapoB for hyperlipidemic (n = 8), normolipidemic (n = 4) dialysis patients and controls (n = 4) were calculated. Dialysis patients had lower VLDLapoB FCRs than controls (p less than 0.05); hyperlipidemic dialysis patients had marginally raised VLDLapoB flux over normolipidemics (p = 0.0508), suggesting apoB production might play a greater role in the pathogenesis of hyperlipidemia. Hyperlipidemics had lower IDLapoB FCRs than controls (p = 0.01). IDLapoB flux was similar in all three groups. The discrepancy in VLDLapoB fluxes between hyperlipidemics and normolipidemics with similar IDLapoB fluxes suggested that VLDLapoB could be directly catabolized in hyperlipidemics. ApoB concentration was increased in VLDL, IDL of hyperlipidemics when compared with normolipidemics (p less than 0.05) and controls (p = 0.01). Hyperlipidemic VLDL plasma levels were relatively enriched with cholesterol when compared with controls, p less than 0.01, and normolipidemics, p less than 0.05. These factors might all contribute towards accelerated atherogenesis in hyperlipidemic dialysis patients. PMID- 2920473 TI - Ultrastructural alterations of glomerular anionic sites in IgA nephropathy. AB - The ultrastructural alterations of glomerular anionic sites were studied in biopsy specimens from 34 patients with IgA nephropathy using polyethyleneimine (PEI). Prominent common findings in the glomeruli of the patients were few PEI particles in electron dense deposits in the mesangial and subepithelial area and marked reduction in glomerular anionic sites covered with deposits. The anionic sites of the glomerular basement membrane (GBM) and epithelial cell surface coat (ESC) appeared unaltered in the patients with hematuria and/or mild proteinuria. But in patients with proteinuria in the nephrotic range, focally discrete loss of anionic sites in the lamina rara externa (LRE) was seen and the number of anionic sites of the ESC were decreased with retraction of the foot processes. The anionic sites of the lamina rara interna showed much less change in these patients. Subepithelial deposits were often seen concomitantly with focal loss of anionic sites in the LRE at the site of the deposits, but subendothelial deposits had little influence on the anionic sites of the neighboring GBM. The anionic sites of GBM that showed focal thinning with small GBM projections were appreciably decreased in number, but those in split GBM were not decreased. These results suggest that either loss of the negative charge on the glomerular capillary wall associated with subepithelial immune deposition or morphological changes of the GBM contribute to the progression of proteinuria in IgA nephropathy. PMID- 2920474 TI - Effects of RA 233 treatment on the adhesive, invasive and metastatic properties of 13762NF rat mammary tumor cells. AB - The pyrimido-pyrimidine analogue RA 233 has pleiotropic and differential effects on cultured tumor cell clones isolated from the 13762NF rat mammary adenocarcinoma. A nonresponsive clone of low metastatic potential (MTC) was not modified in its cell fragility or invasive, adhesive or lung-colonizing properties by RA 233 treatment. In contrast, a drug-responsive clone of high metastatic potential (MTLn3) was rendered less invasive and its cell fragility was decreased with RA 233 treatment, although its adhesiveness to lung microvascular endothelial cells and subendothelial matrix was unaffected by RA 233. Lung colonization of intravenously injected MTLn3 cells in syngeneic rats was significantly increased by RA 233 treatment, whereas spontaneous metastasis from the mammary fat pad to lung sites was decreased, although this decrease was not statistically significant. PMID- 2920475 TI - Association of near-diploid DNA content and N-myc amplification in neuroblastomas. AB - Seventeen neuroblastomas at different clinical stages were analysed for their N myc copy number and flow cytometrically determined DNA content. Aneuploidy was found in 11 patients (65 per cent), whereas the remaining were near-diploid. N myc amplification was found significantly (P less than 0.05) confined to near diploid tumors (3 out of 6 cases). This finding indicates a very selective mechanism of oncogene amplification which is independent of gross chromosomal imbalance and limited to specific loci in the human genome. Association of near diploidy and age at diagnosis older than 24 months was also demonstrated (P less than 0.05). Thus, flow cytometric analysis of DNA content together with N-myc gene dosage allowed us to distinguish two different subsets of neuroblastoma tumors: the first one aneuploid, with single-copy N-myc, usually observed in patients younger than 24 months with localized or IV-S clinical stages; the second one near-diploid, with frequent N-myc amplification, usually observed in patients older than 24 months with advanced clinical stages. PMID- 2920476 TI - Changes in adhesive properties of tumor cells do not necessarily influence metastasizing capacity. AB - BSp6S and BSp73AS are two rat tumors which grow locally after intra-footpad (ifp) application. BSp73ASML and BSp6AS are variants, which metastasize via the lymphatics. Both variants have lost adherence properties, as shown by in vitro culture on plastic surfaces, suggesting that loss of adherence may be accompanied by increased metastasizing capacity. However, after growth of BSp6S and BSp73AS in vitro on poly(2-hydroxyethylmethacrylate) (polyHEMA)-coated plates, which resulted in loss of adherence and spreading, and subsequent intravenous (iv) or ifp injection of non-adherent tumor cells into syngeneic rats, metastasizing capacity was not increased. It is concluded that loss of adherence may facilitate metastatic spread, but certainly is not sufficient for initiation. PMID- 2920478 TI - Symposium: First Canadian Quinolone Conference and Workshop. December 1987, Lake Louise, Alberta. Proceedings. PMID- 2920477 TI - Plasminogen activator activity in clonogenic cell populations separated from a murine fibrosarcoma. AB - Tumor cells from a murine fibrosarcoma (FSa) produce plasminogen activator (PA), a protease that converts the zymogen plasminogen into the trypsin-like enzyme plasmin. Several studies indicate that tumor cell invasion is accompanied by proteolysis and that PA, generated by highly malignant cells, is by far the most ubiquitous protease associated with malignant transformation. Subpopulations of FSa cells were isolated by using density gradient centrifugation and the ability of these populations to form lung colonies was compared with their associated levels of PA production. Five populations of cells from a murine fibrosarcoma were separated in continuous gradients of Renografin in the density range 1.05 1.18 g/cm2. The PA activities of an unseparated control cell lysate and cell lysates of the five separated populations were determined by using [125I]fibrin as a substrate in a reaction between cell lysate and plasminogen. The assay was based on the release of digested [125I]fibrin from the surface of Petri dishes into the supernatant solution, and the results were expressed as a percentage of the total radioactivity. The cell populations collected at densities of 1.05 and 1.09 (B1, B2) were the more clonogenic with relative clonogenic efficiencies of 2.6 and 3.3 times that of the unseparated tumor population, respectively. Analysis for PA demonstrated that enzyme formation was restricted mostly to these two populations. Cells from populations 4 and 5 did not secrete increased amounts of PA and had reduced clonogenic efficiencies compared with the unseparated FSa control population. These results are consistent with the hypothesis that PA activity is correlated with the clonogenicity of tumor subpopulations isolated from a heterogeneous and complex tumor system such as the FSa. PMID- 2920479 TI - The pharmacokinetics and tissue penetration of the fluoroquinolones. AB - There are marked differences among the pharmacokinetic properties of the quinolones. Absorption of norfloxacin, ciprofloxacin, and enoxacin is incomplete, whereas the bioavailability of pefloxacin, ofloxacin and fleroxacin is almost 100%. With the exception of norfloxacin the quinolones can be taken orally or administered by the parenteral route. Maximum serum concentrations vary between 1.5 and 10.7 micrograms/ml depending on the dose and antibiotic given. Respective AUC's of 78 and 5.5 micrograms/ml-h are observed following the administration of 400 mg of either fleroxacin or norfloxacin. Protein binding is low (less than or equal to 30%) and apparent volume of distribution is between 1.5 and 3.1 liters/kg. Pefloxacin undergoes extensive metabolism in the liver (85%) while less than 5% of ofloxacin is transformed. Norfloxacin and ciprofloxacin have the shortest half-lives (+/- 4h), while fleroxacin and pefloxacin have the longest (10-12h). In renal failure, no adjustments are necessary with pefloxacin, while major modifications in dosing interval and/or doses are needed when ofloxacin is given. The pharmacokinetics of the quinolones is disturbed in elderly subjects and cystic fibrosis patients. Concurrent administration of antacids which contain aluminum hydroxide or magnesium hydroxide leads to reduced absorption, while probenecid blocks the tubular secretion of some quinolones. These drugs diffuse rapidly in extravascular fluid, saliva, urine, kidney, prostate, bile and peritoneal fluid. Slightly lower levels can be detected in fibrin clots, cerebrospinal fluid and the heart. Ciprofloxacin offers the best therapeutic ratio (concentration serum-tissue/minimum inhibitory concentration) against Pseudomonas aeruginosa. PMID- 2920480 TI - Antimicrobial therapy: past, present, and future. AB - Antimicrobial chemotherapy is a growth industry in the rapidly changing world of health care. The identification of new pathogens, new treatment modalities, and new issues related to our patterns of antimicrobial use ensure that the practise of Infectious Diseases in 1994 will be markedly different than it has been in 1988. Ongoing adaptation and radical change will both be required of each one of us as we modify our treatment guidelines to ensure that our patients receive optimal antimicrobial therapy for maintaining or regaining their health. PMID- 2920481 TI - Current experience with quinolones in the treatment of urinary tract infection. AB - Urinary infection in some clinical situations remains difficult to treat with standard oral therapy. Particular problems occur in individuals with underlying genitourinary abnormalities, with intolerance to multiple oral agents, with infections due to resistant organisms, and in men with prostatitis. The fluoroquinolone antimicrobials have an extended spectrum of activity compared to standard oral therapy, achieve high concentrations in the urine following the usual therapeutic doses, and are relatively free of major adverse effects. Thus, they may be effective therapy for some of the clinical situations for which current oral therapy is not satisfactory. However, the majority of clinical studies published to date have examined the use of quinolone therapy in the treatment of urinary infection primarily in individuals with a normal genitourinary tract, a group in which an 85-100% cure rate is achieved with standard oral therapy. Further studies of quinolones, particularly in individuals with underlying abnormalities of the genitourinary tract and in men with prostatitis, are required to clarify their role in these clinical situations and to document the extent of the emergence of resistant organisms. Other studies which would compare quinolones, examine more carefully cost effectiveness uses, and evaluate the effectiveness and safety of extended therapy are also needed to identify the appropriate therapeutic niche of this new group of drugs in the management of urinary infection. PMID- 2920482 TI - Role of fluoroquinolones in lower respiratory tract infections. AB - Oral quinolones such as ciprofloxacin are promising agents in the treatment of serious bronchopulmonary infections due to susceptible gram-negative micro organisms such as Haemophilus influenzae, Branhamella catarrhalis, Klebsiella pneumoniae and even Pseudomonas aeruginosa. Their moderative activity against Streptococcus pneumoniae may limit the use of these agents in the treatment of acute exacerbations of chronic bronchitis and in the empiric management of community-acquired bacterial pneumonia. Further prospectively designed studies are needed to address this issue. The ability of quinolones to effectively penetrate bronchial mucosa and to be concentrated within macrophages may afford additional advantage to these agents. They should not be used as a sole agent in the treatment of aspiration pneumonia nor anaerobic pleuropulmonary disease. Quinolones are very active in experimental models of Legionnaire's disease and deserve further clinical study. Ciprofloxacin is a promising alternative to standard parenteral drugs in the management of Pseudomonas aeruginosa infections in adults with cystic fibrosis. The potential for drug interactions with theophylline must be kept in mind for patients on both of these drugs. PMID- 2920483 TI - Role of oral fluoroquinolones as an alternative to traditional parenteral therapy for patients with serious infections. PMID- 2920484 TI - The role of the fluoroquinolones in primary care practice. PMID- 2920485 TI - Prevention and control of resistance to the quinolones. PMID- 2920486 TI - Home oxygen therapy. Outcome of infants discharged from NICU on continuous treatment. AB - Forty-four oxygen-dependent infants were discharged home in oxygen from an NICU during an 8-year period. Survivors were followed for 3 years. The infants' discharge diagnoses were bronchopulmonary dysplasia (BPD) (39), sleep apnea (2), and congenital cardiac defects (3). The five infants who had diagnoses other than BPD all died, but 34 of 39 infants with BPD survived. Supplemental oxygen was discontinued at a mean age of 13.4 months. The infants with BPD experienced health, growth, nutritional, neurodevelopmental and sensory problems that necessitated frequent rehospitalizations and utilization of a variety of medical and support services. PMID- 2920487 TI - The real challenge of "Baby Doe": considering the sanctity and quality of life. PMID- 2920488 TI - Bulimia, tricyclic antidepressants, and mania. AB - Anorexia nervosa and bulimia are common conditions that are difficult to treat effectively. Psychopharmacologic agents, particularly tricyclic antidepressants, are now being used as adjunctive therapy in bulimia. The case of a 15-year-old girl with bulimia who was treated with imipramine and had a severe (and first) manic episode is presented. The complication of drug-induced mania observed in patients treated with tricyclic antidepressants is discussed. PMID- 2920489 TI - Use of antidepressants in bulimia. PMID- 2920490 TI - Nursing bottle caries: characteristics of children at risk. AB - Nursing bottle carries is a pattern of extensive decay in newly erupted maxillary incisors. We examined nutritional, demographic, and behavioral characteristics of children with this condition and age/sex-matched controls, generating a profile of factors associated with increased risk for the development of this disease. Parents of 24 consecutive bottle caries patients seen in a private pediatric dental office completed a questionnaire. Controls were children receiving routine primary pediatric health services at a university based clinical office. Children with bottle caries were more likely to be living in a single parent household (p = 0.005). A higher incidence of sleep difficulties and strong temper also was reported (p = 0.05). Cases were more likely to take the bottle to bed and, to an older age than controls. They received less professional advice regarding weaning as well as less fluoride supplementation (p = 0.025). Clinical recognition of this profile may foster provision of specific anticipatory guidance resulting in primary prevention of this condition. PMID- 2920491 TI - Paraplegia after lumbar puncture. In an infant with previously undiagnosed hemophilia A. Treatment and peri-operative considerations. AB - We report a 3-month-old infant who became paraplegic from an epidural hematoma caused by a diagnostic lumbar puncture for work-up of sepsis. The differential diagnosis of the cause of paraplegia was epidural hematoma formation versus spinal abscess. Hemophilia A was diagnosed when coagulation studies were discovered to be abnormal, and non-contrast CT scan revealed an epidural mass with spinal cord displacement. The coagulopathy was rapidly corrected preoperatively with an infusion of cryoprecipitate. A medially limited bilateral T8-L4 laminectomy allowed complete evacuation of the hematoma with maximum preservation of normal bone tissue, but no clinical improvement resulted. Coagulopathy should be highly suspect in an infant who becomes paraplegic after lumbar puncture. The coagulopathy may be rapidly corrected with deficient factor replacement, allowing major spinal surgery to be performed safely. PMID- 2920492 TI - Recurrent bacterial meningitis. Secondary to malformation of the inner ear. AB - A 5-year-old girl with congenital sensorial deafness experienced four episodes of bacterial meningitis in a 13-month period. On the fourth episode, an extensive search for the cause of recurrent meningitis was conducted. Complete immunologic studies, humoral, cellular, and phagocytic, yielded negative results. Precise otological examination, i.e., skull roentgenograms, an inner ear target CT scan, and puncture of the eardrum, was attempted, which disclosed the inner ear malformation (Mondini's anomaly) and a cerebrospinal fluid (CSF) fistula. CSF discharge from the oval window was repaired surgically. Extensive otologic evaluation should be conducted in patients with recurrent bacterial meningitis. PMID- 2920493 TI - Nail size in normal infants. Establishing standards for healthy term infants. AB - The nails of 48 healthy infants of 39 to 41 weeks' gestation were measured with dial calipers to establish both a method for measurement of nails and standards of nail size. Nail width and length were measured directly, and an estimated area was calculated. Nail area was compared between sexes and races and was not found to differ significantly except between races for the first fingernail. A description of the term newborn nail is presented. PMID- 2920494 TI - Is it sexual abuse? Confusion caused by a congenital anomaly of the genitalia. AB - Because of the increasing number of reports of sexual abuse of children, pediatricians should become more familiar with the examination of the genitalia of prepubertal children and learn to recognize physical indicators of abuse. Although some physicians may not recognize abnormal findings on examination, in other cases, unusual physical findings may be reported erroneously as possible abuse. The authors report a case of an unusual genital finding in a child which was suspected initially as being caused by sexual abuse but was subsequently determined to be a congenital anomaly. An external examination using a colposcope was useful in delineating the normal appearance of the tissues in question. PMID- 2920495 TI - Education on the concept of essential drugs and rationalized drug use. PMID- 2920496 TI - Ferrous sulfate reduces levodopa bioavailability: chelation as a possible mechanism. AB - This study examined the effect of ferrous sulfate, a widely used iron treatment, on levodopa bioavailability in normal subjects. A 250 mg tablet of levodopa was taken with and without a 325 mg tablet of ferrous sulfate by eight normal subjects in a randomized crossover trial. When levodopa was taken with ferrous sulfate there was a 55% decrease in peak levodopa levels (3.6 +/- 2.6 vs 1.6 +/- 0.82 nmol/ml; p less than 0.05) and a 51% decrease in AUC (257 +/- 133 vs 125 +/- 51 nmol.min/ml; p less than 0.01). Persons with the highest peak levodopa levels and AUC after levodopa alone had the greatest reduction in peak levodopa levels and AUC after levodopa ingestion with ferrous sulfate. Iron in its ferrous state is oxidized rapidly to the ferric state in the presence of levodopa at pHs found in the small intestine. In the ferric state, iron binds very strongly to levodopa. Chelation of iron by levodopa is the likely mechanism for this drug interaction. The clinical significance of this interaction is yet to be established. PMID- 2920497 TI - Adaptive control of etoposide administration: impact of interpatient pharmacodynamic variability. AB - We sought to use a previously derived pharmacodynamic model for 72-hour etoposide infusions to adaptively control administration of this agent and to demonstrate that more predictable toxicity could be obtained with this dosing scheme. A randomized crossover study design was used to compare "standard" dosing (125 mg/m2/day) to adaptive control, with dose adjustment at 28 hours based on the 24 hour plasma level. A total of 31 patients received 86 cycles of chemotherapy, 36 by standard dosing and 50 by adaptive control. However, there was no demonstrable advantage to the adaptive control scheme, because of apparent bias of the previous model. A new model was proposed that also included serum albumin, performance status, and prior RBC transfusions as measures of interpatient pharmacodynamic variability. We conclude that adaptive control dosing of etoposide is feasible but that the therapy must be individualized for both pharmacokinetic and pharmacodynamic variability. PMID- 2920498 TI - Effect of quinolones on caffeine disposition. AB - Six healthy volunteers received a single caffeine dose after pretreatment with norfloxacin, pipemidic acid, or placebo in a crossover, randomized, single-blind clinical trial. Quinolones altered the pharmacokinetics of caffeine, with a significant increase in the AUCs and a decrease in plasma clearance. The elimination half-life increased significantly with pipemidic acid. The apparent volume of distribution, mean renal clearance, and time to reach maximum caffeine concentrations remained unaltered. There was a decline in caffeine metabolite levels in the 24-hour urine samples for both quinolone treatments, suggesting that pipemidic acid and, to a lesser degree, norfloxacin inhibit metabolism of the N-demethylation pathways of caffeine. The practical consequence of this observation could be caffeine accumulation during repeated intake of coffee. In two additional healthy volunteers under a controlled multiple-dose regimen of caffeine ingestion, administration of pipemidic acid for 2 days caused a fourfold increase in the plasma concentrations of caffeine. PMID- 2920499 TI - Effect of yohimbine on blood pressure in patients with depression and orthostatic hypotension induced by clomipramine. AB - Orthostatic hypotension, one of tricyclic antidepressant treatment's side effects, is also a factor in limiting adequate antidepressant dosing. We tested in a double-blind, crossover, placebo-controlled study the effect of low doses (4 mg/t.i.d.) of yohimbine in 12 patients with depression with clomipramine-induced orthostatic hypotension. Yohimbine, a selective alpha 2-adrenoceptor antagonist, had a favorable effect in orthostatic hypotension and induced a significant increase in blood pressure. A pharmacodynamic and pharmacokinetic interaction between yohimbine and clomipramine or demethylclomipramine was discussed. PMID- 2920500 TI - Individual variability in the blood pressure response to intravenous phenylpropanolamine: a pharmacokinetic and pharmacodynamic investigation. AB - The intersubject variability in blood pressure response to 0.44 mg/kg intravenous phenylpropanolamine (d,l-norephedrine) was studied in 10 normal subjects. A phenylpropanolamine or placebo infusion was administered over 45 minutes on separate days according to a double-blind, balanced protocol. Blood pressure increased by 24 +/- 13/16 +/- 7 mm Hg (systolic/diastolic, mean +/- SD) after the phenylpropanolamine infusion and was statistically different from the placebo infusion response (7 +/- 5/8 +/- 3 mm Hg). Phenylpropanolamine infusions were terminated early in two subjects (hyperresponders) after 0.31 and 0.23 mg/kg because of excessive increases in blood pressure (52/30 and 34/21 mm Hg, respectively). The hyperresponders had the lowest peak serum phenylpropanolamine concentrations. These data suggest that considerable intersubject variability exists in the blood pressure response to intravenous phenylpropanolamine. A pharmacokinetic basis for the variability in response to racemic phenylpropanolamine was not observed. A relationship did not exist within the group between blood pressure effect and serum concentration but did exist within each subject. Therefore phenylpropanolamine's blood pressure effect in an individual cannot be predicted solely from a serum concentration of racemic drug. PMID- 2920501 TI - Monoamine oxidase inhibition by phenelzine and brofaromine in healthy volunteers. AB - The two monoamine oxidase (MAO) inhibitors phenelzine and brofaromine given for 2 to 3 weeks were compared in six volunteers. Blood pressure sensitivity to intravenous tyramine increased 2.6-fold during phenelzine (60 mg/day) and 4.8 fold during brofaromine, whereas sensitivity to oral tyramine increased more during phenelzine (15.7-fold vs 8.5-fold). After withdrawal of phenelzine, pressor sensitivity to oral tyramine returned to control values within 2 and for more than 8 weeks. Relative bioavailability of conjugated tyramine was elevated sixfold by brofaromine and 11.6-fold by phenelzine. Urinary elimination of tryptamine increased during phenelzine and brofaromine to 12.7-fold and threefold, respectively. 3-Methoxy-4-hydroxyphenylglycol (MHPG) and 3-methoxy-4 hydroxymandelic acid (VMA) excretion decreased during brofaromine significantly by 72% and 49%, respectively. The nonsignificant decrease of MHPG excretion and the increase of intravenous tyramine pressor sensitivity caused by phenelzine are significantly related. The data suggest that the selective reversible MAO-A inhibitor brofaromine has a larger therapeutic safety than phenelzine. PMID- 2920502 TI - Safety, tolerability, and pharmacologic activity of multiple doses of the new platelet activating factor antagonist WEB 2086 in human subjects. AB - The safety, tolerability, and pharmacologic activity of WEB 2086, a novel, specific platelet activating factor antagonist, were examined in two double blind, placebo-controlled, within-subject crossover studies. In each study, WEB 2086 (three times 40 mg/day or three times 100 mg/day) was administered for 7 days to 12 healthy volunteers. Pharmacologic activity of the compound was monitored with ex vivo platelet activating factor-induced platelet aggregation. Multiple administration of WEB 2086 resulted in a continuous, almost complete inhibition of this aggregation. Nevertheless, no clinically significant drug related effects on vital and laboratory parameters or obvious drug-dependent adverse reactions were observed. In conclusion, the performed studies confirmed earlier findings that WEB 2086 was an effective platelet activating factor antagonist in human beings and, furthermore, showed no side effects that would provide objections against further clinical trials with this substance in patients. PMID- 2920503 TI - Nitrendipine versus hydrochlorothiazide in hypertensive patients over 70 years of age. AB - The effects of nitrendipine and hydrochlorothiazide were studied in hypertensive elderly patients. Blood pressure was reduced (p less than 0.01) by both nitrendipine (13/10 +/- 4/3 mm Hg [n = 15], mean +/- SE) and hydrochlorothiazide (25/11 +/- 4/2 mm Hg [n = 16]). After hydrochlorothiazide, plasma glucose, uric acid, and renin activity increased and plasma potassium levels decreased. Edema and flushing were the main adverse reactions during nitrendipine. The response of blood pressure and heart rate to head-up tilt were not significantly different under both treatments. However, the effects of both drugs on diastolic blood pressure and norepinephrine responses to head-up tilt differed significantly. We conclude that, in the elderly, hydrochlorothiazide lowers systolic blood pressure more effectively than nitrendipine. However, nitrendipine does not have any of the potentially harmful metabolic side effects that were found during hydrochlorothiazide therapy. The clinical significance of a lower vasoreactivity during nitrendipine, as was found with the head-up tilt test, has to be established. PMID- 2920504 TI - Influence of absorbable and nonabsorbable lipids and lipidlike substances on drug bioavailability. AB - The influence of three diets (olestra, triglyceride oil, and water) on the bioavailability of a single dose of propranolol, diazepam, norethindrone, and ethinyl estradiol was evaluated. For each drug the diets were randomly administered in a crossover fashion; a period of at least 14 days separated each of the drug studies. Blood samples were obtained before and after the oral administration of test drug and diet. Specific timing of blood samples varied for the respective drugs. AUCs were determined by the trapezoidal method. There were no statistical differences observed in the absorption of the various drugs evaluated in this study when administered with olestra, triglyceride oil, or water, except that the time to peak concentration of diazepam was significantly longer with the triglyceride oil than with olestra or water. PMID- 2920505 TI - Effects of time of dose in relation to food on the bioavailability of Theo-Dur Sprinkle at steady state in asthmatic children. AB - The effects of administration of Theo-Dur Sprinkle in the fasting state (phase A), 10 minutes before food (phase B), and immediately after food (phase C) were investigated in 12 children with asthma aged 5 to 9 years at steady state. The AUC during the dosing interval was significantly reduced in phases B and C compared with phase A, and bioavailability relative to the fasting state was reduced to 77% +/- 15% (range 61% to 104%) in phase B and 70% +/- 16% (range 40% to 103%) in phase C. The average plasma theophylline concentration during the dosing interval and Cmax were also significantly reduced in phases B and C compared with phase A. The morning predose plasma theophylline concentration in phase B was 22% lower than the predose concentration with Theo-Dur tablets taken 10 minutes before breakfast. The diurnal variation in predose plasma theophylline concentrations was increased from 28% in phase A to 63% in phase C. There was no significant difference in any parameter between administration 10 minutes before food and immediately after food. PMID- 2920506 TI - Assessment of the debrisoquin and dextromethorphan phenotyping tests by gaussian mixture distributions analysis. AB - From a sample of 149 unrelated Spaniards, individuals were phenotyped for their ability to hydroxylate debrisoquin and O-demethylate dextromethorphan. The distribution of urinary metabolic ratios for each test was analyzed by univariate gaussian mixture distributions analysis to determine the number of populations, the mean and standard deviation of the metabolic ratios for each population, and the proportion belonging to each population. For the 124 subjects phenotyped with both the debrisoquin and dextromethorphan tests a bivariate analysis was performed. The results demonstrate that both tests similarly separated this sample into two populations, with 10% belonging to poor metabolizer phenotypes. In addition, the correlation between the metabolic ratios from each test is significant, indicating that they are measuring the same biologic trait and the certainty of correctly identifying the debrisoquin oxidation phenotype of an individual is improved by using the results of both tests. PMID- 2920507 TI - An insurance policy to reduce the risk of dying from breast cancer. PMID- 2920508 TI - Tibia vara caused by focal fibrocartilaginous dysplasia. AB - A case of severe unilateral tibia vara in a young boy is reported. The clinical and radiological features were identical to the only three reported cases of focal fibrocartilaginous dysplasia. With conservative management the child showed a complete recovery. The importance of recognising this condition is emphasised, as unnecessary surgery may be avoided. The radiologist can play a major role in making the diagnosis. PMID- 2920509 TI - Superior aspect of the perirenal space. PMID- 2920510 TI - In defence of the duodenum. PMID- 2920511 TI - Unilateral orbital edema following the intravascular injection of contrast medium. PMID- 2920512 TI - Relapsing polychondritis. PMID- 2920513 TI - The accuracy of volumetric measurement of high-grade gliomas. AB - To assess the accuracy of volumetric measurement of high-grade intracranial gliomas by computed tomography (CT), the scans of 26 patients were studied retrospectively. Twenty patients had only pre-treatment scans while six had scans both before and after chemotherapeutic treatment. Tumour volumes were measured separately by two observers, each on two occasions. A significant intraobserver variation in volumetric measurement was encountered, as well as a systematic variation between the observers; one radiologist consistently reading higher than the other. The after treatment readings were more variable than the pre-treatment readings, and most changes in tumour volume following treatment were obscured by the intra-observer variation. This study provides further evidence of the limitations of volumetric measurement as a means of assessing the response of high-grade gliomas to treatment. PMID- 2920514 TI - Can computed tomography be relied upon to detect skull fractures? AB - Skull fractures were detected on plain films in 63 of 100 consecutive head injured patients admitted to a neurosurgical unit. On routine computed tomographic (CT) lateral scout films, only 58% of lateral fractures were detected and there was a false positive rate of 12%. None of the anterior or posterior fractures was seen. On the routine axial CT cuts only 22.5% of fractures were detected. When examined at bone window settings, 76% of vertical and 37.5% of oblique linear fractures were detected but none of the horizontal fractures. All comminuted and depressed fractures were demonstrated when the axial cuts were examined at bone window settings and in all but one case by the scanogram and at routine brain window settings. Basal fracture extent was better shown by axial CT than on plain films, especially at bone window settings. Recommendations are made regarding the use of CT in the detection of skull fractures. PMID- 2920515 TI - Computed tomography in the management of nasopharyngeal carcinoma. AB - Nasopharyngeal carcinoma (NPC) is one of the common cancers in China. According to mass surveys, the incidence of NPC in some areas of Guangdong is 39.84/100,000. Due to its high contrast resolution CT has the ability to show not only superficial abnormality but also deep infiltration of the fasciae and muscles of the parapharyngeal region. Computed tomography scanning was performed on more than 1000 patients with NPC in the Tumour Hospital in the 2 years from 1984 to 1986. The role of CT scanning in NPC can be summarised as: (1) detection of primary lesions not accessible to pharyngoscopy; (2) determination of the extent of disease; (3) clinical staging; (4) radiotherapy planning; (5) follow up evaluation; (6) the differentiation of recurrence and radiation damage to the brain; and (7) the demonstration of distant metastasis. In contrast to the concept of jugular chain metastasis via the postero-lateral pharyngeal lymph nodes, our material has demonstrated that the lesion most probably spreads to the carotid sheath area directly from the pharyngeal lesion. The tendency of submucosal spread of NPC is emphasised. PMID- 2920516 TI - Normal lymph node size in the mediastinum: a retrospective study in two patient groups. AB - The size and number of normal mediastinal lymph nodes seen on computed tomography were studied retrospectively in 110 patients from the Royal Marsden Hospital, Sutton, and St Bartholomew's Hospital, London. The mediastinum was divided into four areas. Lymph nodes were seen in 81% of patients. The number of patients with nodes in a specific area varied from 28% in the right superior mediastinum to 46% in the pretracheal retrocaval space. Seventeen per cent of the areas studied contained one node, 11% contained two or three nodes and 4% had three nodes. Fewer nodes were seen in patients with sparse mediastinal fat. Sixty-seven per cent of patients had nodes measuring 5 mm or less in maximum transverse diameter and 21% of patients had one or more nodes of 6-10 mm. Only a single calcified node measured more than 10 mm. We conclude that the majority of nodes are 5 mm or less in diameter and that almost all normal nodes measure 10 mm or less. PMID- 2920517 TI - Shadows over screening mammography. PMID- 2920518 TI - The value of computed tomography in the diagnosis and management of bronchiectasis. AB - In order to evaluate the usefulness of computed tomography (CT) in the diagnosis and management, as distinct from only the diagnosis, of bronchiectasis, we retrospectively reviewed the clinical, lung function, and radiological data of 38 patients suspected of having the disease. All had chest radiographs, CT scans, and bronchograms. The approach was to examine the radiological investigations with the clinical data in three stages: I, chest radiograph; II, CT; III, bronchography (BG), as if they were newly presenting cases. At the end of each stage, a decision was made either to proceed to the next stage or to stop because further investigation was considered unlikely to alter management. Apparent normality, equivocal abnormality, or unilateral abnormality were criteria for proceeding. Unfitness for surgery, unequivocal bilateral disease, or mild disease were criteria for stopping after a firm diagnosis had been made. We stopped at stage I in four patients (11%) because the chest radiograph showed bilateral bronchiectasis and two had poor lung function. We stopped at stage II in 15 patients (39%): 12 had bilateral disease on CT; three had unilateral disease on CT but their clinical features were so mild that BG was considered unjustified. Scrutiny of the CT and BG films of those patients who were judged not to require CT or BG in the retrospective review confirmed that these would not have altered their management. Of the remaining 19 patients who proceeded to stage III, BG was useful in 15 (39%) by confirming or refuting CT findings, but was not useful in four (11%) because of underfilling. We conclude that optimal use of chest radiographs and CT in patients suspected of having bronchiectasis can significantly reduce the necessity of performing BG. PMID- 2920519 TI - A comparison of radiation doses to the breast in computed tomographic chest examinations for two scanning protocols. AB - Compared with other radiological examinations in which the breasts are directly exposed, the breast doses involved in computed tomographic (CT) chest examinations are high. A CT protocol which reduces such breast dose has been investigated. Breast doses have been measured for contiguous 10 mm scans and interspaced 3 mm scans. Differences in the breast doses were found between the left and right breasts for both scanning protocols. The dose associated with the interspaced scans was lower by a factor of about two compared with that for the contiguous scans. PMID- 2920520 TI - Aortic displacement on computed tomography of idiopathic retroperitoneal fibrosis. AB - We present two cases of proven idiopathic retroperitoneal fibrosis in which displacement of the aorta from the spine (caused by the presence of tissue posterior to the aorta) was demonstrated on computed tomography, an appearance which has not been reported previously. PMID- 2920521 TI - Oesophageal tears during pneumatic balloon dilatation for the treatment of achalasia. AB - Fifty-eight contrast studies of the oesophagus, performed in patients shortly after balloon dilatation for the treatment of achalasia, were reviewed for evidence of perforation. Forty-nine examinations (85%) were normal and nine studies (15%) were abnormal. Three main radiological patterns were observed. Complete rupture of the oesophagus occurred in two cases. Incomplete tears of the oesophageal wall were present in seven cases: in one patient there was a linear mucosal tear while in six patients there was a localised outpouch or diverticulum. All patients with abnormal contrast studies were successfully managed conservatively. The range of radiological appearances of the distal oesophagus following balloon dilatation should be recognised to avoid unnecessary surgical intervention. PMID- 2920522 TI - Ulcerogenic choledochoduodenal fistula. AB - Spontaneous choledochoduodenal fistula is a rare form of biliary enteric fistula which is usually related to peptic ulcer disease and therefore is seen more often in men. This is in contrast to the more common cholecystoduodenal fistula which is associated with calculous gall-bladder disease and occurs predominantly in women. We report two cases diagnosed by radiology following unhelpful laparotomy. PMID- 2920523 TI - The fragmented staghorn calculus: a radiological sign of pyonephrosis. AB - Staghorn calculi may cause several complications, particularly important being the development of pyonephrosis due to long-standing infection. We describe four patients who presented with either a marked systemic illness or a loin mass due to pyonephrosis. In each patient, the plain abdominal radiograph showed a fragmented staghorn calculus, which is suggested as a radiological sign of pyonephrosis and indicative of the need for surgical attention. PMID- 2920524 TI - Fatal outcome of pelvic radiotherapy for carcinoma of the cervix in a patient with systemic lupus erythematosis. AB - Although there is an impression that patients with connective tissue disorders tolerate radiotherapy less well than other patients, this is not well documented in the literature. We present the case of a patient with a 7-year history of systemic lupus erythematosis who developed fatal pelvic necrosis as an unexpectedly severe complication after radiotherapy for carcinoma of the cervix. PMID- 2920525 TI - Primary cutaneous neuroendocrine (Merkel cell or trabecular carcinoma) tumour of the skin: a radioresponsive tumour. AB - Four patients with primary neuroendocrine carcinoma of the skin (Merkel cell or trabecular carcinoma) are reported to document their response to radiotheraphy. In three patients there was complete response following radiation treatment, with no local recurrence, whilst the other patient died later with distant metastases. In one patient, post-operative irradiation after excision of an involved local node prevented the growth of further tumour in this nodal group but the unirradiated primary site recurred after initial wide local excision only. This rare tumour appears to be radioresponsive, and although more clinical data are required, we would advocate a wider study of radiotherapy to the primary lesion after biopsy or excision biopsy, in association with prophylactic nodal irradiation. These tumours occur predominantly in elderly people in whom the avoidance of extensive surgery is particularly desirable. PMID- 2920526 TI - A case of breast carcinoma with sarcomatous metaplasia. AB - We report the distinct mammographic appearance of a breast carcinoma in a woman of 58 years, which proved on histology to be adenocarcinoma with metaplasia to osteosarcoma. The unusual appearance may alert radiologists, surgeons and pathologists to the possibility of an uncommon tumour. PMID- 2920527 TI - A method of quantifying sinus arrhythmia: parallel effect of respiration on P-P and P-R intervals. AB - 1. The electrocardiogram was recorded for 3 min during spontaneous respiration in 70 subjects aged 15-86 years who were in sinus rhythm. Using a signal-averaging approach, the presence of respiratory variation of P-P intervals was analysed by multiple regression against a cosine function (cosinor analysis). 2. By cosinor analysis the phase of respiration when the intervals were longest was determined, together with the amplitude of the variation of the intervals around their mean value. 3. Respiratory variation of P-P intervals (respiratory sinus arrhythmia) was demonstrated in 84% of subjects; its amplitude decreased with age and respiratory rate. On average, the duration of P-P intervals varied by 2.8% around the mean, and the maximum duration occurred around the time of end-expiration. 4. By cosinor analysis, and allowing for variation of heart rate, P-R intervals showed an independent respiratory variation in 39% of cases, and its average amplitude was 1.2% around the mean. 5. The respiratory variation of P-R and P-P intervals showed similar phase relationships to respiration, suggesting that during respiration there is parallel alteration of sinoatrial and atrioventricular node function. PMID- 2920528 TI - Paradoxical effect of respiration on ventricular rate in atrial fibrillation. AB - 1. In 50 subjects with atrial fibrillation we have attempted to demonstrate variation of ventricular rate with respiration, as evidence of cardioregulatory reflex activity. 2. The electrocardiogram was recorded for 3 min during spontaneous respiration. The presence of respiratory variation of R-R intervals was analysed by multiple regression against a cosine function (cosinor analysis), making it possible to determine the phase of respiration when the intervals were longest. 3. Variation in ventricular rate with respect to respiration was demonstrated (P less than 0.05) in seven (14%) cases. On average, R-R intervals were longest at the end of inspiration; this contrasts with sinus rhythm where P P, P-R and R-R intervals are longest around the time of end-expiration. 4. These results suggest that in atrial fibrillation the beat-to-beat ventricular rate may be under the influence of cardioregulatory reflexes, but the effect of respiration is weak and paradoxical. PMID- 2920529 TI - Effect of passive muscle stretching in osteoarthritis of the hip. AB - 1. Twenty-five minute daily muscle stretching, perpendicular to the fibre direction of the adductor muscles without movement of the hip, was performed in patients with osteoarthritis of the hip. 2. Before and after treatment hip abduction was measured and muscle biopsies were taken for analysis of fibre cross sectional areas of type 1 and type 2 fibres as well as adenosine 5'-triphosphate, creatine phosphate and glycogen contents. 3. From the results it is concluded that passive muscle stretching leads to a significant increase in hip abduction of 8.3 degrees (P less than 0.05). There was also a significant increase of type 1 and type 2 fibre cross-sectional area and of glycogen content after the treatment period (P less than 0.05), but the concentrations of adenosine 5' triphosphate and creatine phosphate did not change significantly. PMID- 2920530 TI - Inter-relationship between urinary kallikrein-kinins and arginine vasopressin in man. AB - 1. Physiological saline solution was infused in nine normal subjects and six patients with central diabetes insipidus (DI). At 120 min after the start of infusion, arginine vasopressin (AVP) was injected intramuscularly. Urine was collected in 30 min fractions before and after AVP administration. 2. The urinary excretions of kallikrein-like activity (KAL-A) (S-2266 hydrolysis activity) and immunoreactive kinins (i-kinins) were significantly lower in patients with DI than in normal subjects before AVP administration, while there were no differences in plasma renin activity, plasma aldosterone concentration, creatinine clearance and blood pressure between the two groups, except for a marked water diuresis in patients with DI. The urinary excretion of KAL-A and i kinins correlated positively with the urinary excretion of AVP. 3. AVP administration increased both plasma AVP and urinary excretion of AVP to similar levels in both groups. As a result, urine volume decreased to a greater degree in patients with DI than in normal subjects. In contrast, the urinary excretions of KAL-A and i-kinins were increased by AVP administration, with a greater response in normal subjects than in the patients with DI. 4. After overnight fasting, acute water loading was carried out orally for 15 min in six normal subjects. At 30 min plasma AVP was suppressed by water loading to almost the basal level found in patients with DI. Urinary excretions of KAL-A and i-kinins in the first 30 min fraction after loading were also suppressed to the basal level in patients with DI. Later, the urinary excretion of KAL-A increased together with the increase in urine flow. Urine volume and free water clearance markedly increased except in the first 30 min fraction, compared with the control period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2920531 TI - Erythrocytes alter the pattern of renal hypoxic injury: predominance of proximal tubular injury with moderate hypoxia. AB - 1. The distribution of morphological injury was assessed qualitatively and quantitatively in the perfused rat kidney in vitro at controlled rates of oxygen delivery in the presence of low concentrations of erythrocytes. 2. In control kidneys (total oxygen delivery approximately 32 mumol/min per kidney) no injury was seen in the medullary thick ascending limb of Henle's loop (MTAL) whilst 11 +/- 5(SD)% of proximal tubules sustained damage. 3. Mild hypoxia (total oxygen delivery approximately 28 mumol/min per kidney) produced little or no injury to MTAL, namely 6 +/- 4(SD)% and 3 +/- 3% of tubules damaged, respectively. In contrast, both groups sustained extensive damage to proximal tubules, averaging 46 +/- 13% (P less than 0.01 vs control) and 84 +/- 14% (P less than 0.001 vs control), respectively. This damage was equally distributed between the superficial and deep cortex. 4. Comparison with morphometric data obtained previously from cell-free-perfused rat kidneys [P.J. Ratcliffe, Z. H. Endre, S. J. Scheinman, J. D. Tange, J. G. G. Ledingham & G. K. Radda (1988) Clinical Science 74, 437-448] showed that (a) erythrocytes prevent hypoxic damage to the MTAL at mild and moderate levels of hypoxia; (b) when oxygen delivery rates are matched between cell-free- and erythrocyte-perfused kidneys, proximal tubular injury is greater in the presence of erythrocytes; (c) when arterial partial pressure of oxygen is matched between cell-free- and erythrocyte-perfused kidneys, the degree of proximal tubular injury is similar. 5. The data suggest that the proximal tubule and not the MTAL is the nephron segment most at risk of hypoxic injury in vitro. PMID- 2920532 TI - Urinary albumin excretion and blood pressure in the general population. AB - 1. Twenty-four hour urinary albumin excretion rate was measured by a sensitive radioimmunoassay in 99 male and 100 female randomly selected factory workers, aged between 20 and 60 years. 2. The median (range) albumin excretion rates for men and women of 4.67 (1.0-25.8) and 5.25 (0.2-33.0) mg/24 h, respectively, were not significantly different. 3. No correlation was established between diastolic, systolic or mean arterial blood pressure and albumin excretion rate for the whole group. 4. Twenty-eight subjects with systolic and/or diastolic blood pressures greater than or equal to 140/90 mmHg (18.7/12.0 kPa) showed a positive correlation between mean arterial blood pressure and albumin excretion rate (r = 0.412, P less than 0.01). 5. There was no significant relationship between number of cigarettes smoked, age or alcohol intake and albumin excretion rate. 6. The data suggest that in the general population albumin excretion rate is variable and not dependent on blood pressure, but at blood pressures greater than 140/90 mmHg (18.7/12.0 kPa) albumin excretion rate may become pressure dependent, although high albumin excretion rates were sometimes found in subjects with blood pressures less than 140/90 mmHg (18.7/12.0 kPa). PMID- 2920533 TI - Transamination of methionine in humans. AB - 1. This study was designed to investigate the transamination pathway of methionine in humans. 2. Evidence is provided that methanethiol and its metabolites are formed via transamination of methionine. 3. Gas-liquid chromatography was used to measure serum and urinary transamination metabolites of methionine: 2-keto-4-methylthiobutyrate, 3-methylthiopropionate and methanethiol, and the metabolites of methanethiol, dimethylsulphide, protein-S-S CH3 (a mixed disulphide of blood proteins and methanethiol) and X-S-S-CH3 (a mixed disulphide of methanethiol and another thiol with an unknown component X). 4. Methionine and the transamination intermediates were measured in 10 normal subjects, in six normal subjects after L-methionine loading (0.1 g/kg body weight) and in a male patient with hepatic methionine adenosyltransferase (EC 2.5.1.6) deficiency. 5. In the patient with methionine adenosyltransferase deficiency, at least 20% of methionine was degraded via transamination. In normal subjects transamination of methionine did exist but was quantitatively not important in methionine catabolism, not even after methionine loading. 6. The results of this study might be of importance for future studies on the role of methanethiol in hepatic encephalopathy. PMID- 2920534 TI - Effect of liver disorders on ethanol elimination and alcohol and aldehyde dehydrogenase activities in liver and erythrocytes. AB - 1. Liver biopsies were performed in healthy control subjects and in subjects with alcoholic and non-alcoholic liver disease in order to examine alcohol dehydrogenase (ADH; EC 1.1.1.1) and aldehyde dehydrogenase [ALDH; aldehyde dehydrogenase (NAD+); EC 1.2.1.3] activities. Erythrocyte ALDH and ethanol metabolism were also investigated in the same subjects. 2. Fifteen per cent of the subjects studied (seven of 48 subjects tested) presented atypical ADH activity, characterized by elevated activity at pH 7.4 or 8.8 compared with that found in subjects with the usual ADH form. However, the ethanol elimination curves obtained in two subjects with atypical ADH were indistinguishable from the kinetics of the group with normal ADH. Subjects displaying atypical ADH activity showed normal liver and erythrocyte ALDH activities. 3. Considering only the subjects with the normal ADH form, hepatic ADH activity was unaltered in subjects with non-alcoholic liver disease (chronic hepatitis or cirrhosis) and in those with alcoholic steatosis. Subjects with alcoholic hepatitis or alcoholic cirrhosis showed a lower ADH activity compared with the healthy control group. 4. In spite of the changes detected in subjects with alcoholic liver disease, curves of blood ethanol concentration after oral administration of 0.4 g of ethanol/kg were indistinguishable between the alcoholic hepatitis group and the control group. 5. Hepatic ALDH activity, assayed at 300 mumol/l acetaldehyde, was found to be diminished in all liver pathologies investigated, regardless of their aetiology. Nevertheless, erythrocyte ALDH activity was not modified in subjects with non-alcoholic or alcoholic liver disease. As a result of these findings, no relationship was found between hepatic and erythrocyte ALDH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2920535 TI - Maternal zinc during oral iron supplementation in pregnancy: a preliminary study. AB - 1. To investigate the possible effect of iron ingestion on maternal zinc status, one group of women was given 94 mg of iron per day as ferrous sulphate with multivitamins during the second and third trimesters of their pregnancies and another, control, group was given a placebo of multivitamins without iron. 2. The subjects given iron developed significantly lower plasma zinc concentrations than those in the control group. This effect on zinc was maximal by 6 weeks, whilst that on maternal iron status was slower. 3. There was no parallel decrease of zinc concentration in maternal mixed leucocytes, or of plasma heatlabile alkaline phosphatase activity, suggesting that there was a redistribution of zinc between plasma and tissues. 4. The results indicate that iron supplementation during pregnancy alters the disposition of zinc in the mother. PMID- 2920536 TI - Platelet intracellular free calcium concentration in normotensive and hypertensive pregnancies in the human. AB - 1. Basal and stimulated platelet intracellular free calcium concentrations were measured in non-pregnant women and in third trimester patients who were either normotensive or who had pregnancy-induced hypertension or pre-eclampsia. There were 15 subjects in each group. 2. A trend for a reduction of the maximal response of platelet calcium levels to stimulation by 5-hydroxytryptamine was seen in pregnant groups compared with nonpregnant subjects, but this was significant only in pre-eclampsia. 3. No significant differences in basal or adenosine 5'-pyrophosphate-stimulated levels of platelet intracellular free calcium concentration were observed between the four groups. 4. These results illustrate that basal platelet calcium levels are unchanged in hypertension of pregnancy. Alterations in basal platelet calcium levels may not be involved in the platelet activation that is a feature of pre-eclampsia. PMID- 2920537 TI - Perception of rotated forms: a theory of information types. AB - The present article proposes a theory of form perception in an attempt to understand puzzling problems in mental rotation and in perception of forms rotated in the frontal-parallel plane. According to the theory, it is critical to distinguish four types of information. They result from the orthogonal combination of two binary distinctions: information can be orientation-free or orientation-bound, elementary or conjunctive. The theory provides an explanation as to when and why mental rotation has to be performed. If two forms can be discriminated only on the basis of conjunctive orientation-bound information, mental rotation or some other functionally equivalent strategy is required. Mental rotation is unnecessary if the forms differ in either type of orientation free information, provided that the difference is actually encoded as such. This explanation along with the proposed distinctions among the four types of information was supported by two mental rotation experiments and three visual search experiments. PMID- 2920538 TI - Critical period effects in second language learning: the influence of maturational state on the acquisition of English as a second language. AB - Lenneberg (1967) hypothesized that language could be acquired only within a critical period, extending from early infancy until puberty. In its basic form, the critical period hypothesis need only have consequences for first language acquisition. Nevertheless, it is essential to our understanding of the nature of the hypothesized critical period to determine whether or not it extends as well to second language acquisition. If so, it should be the case that young children are better second language learners than adults and should consequently reach higher levels of final proficiency in the second language. This prediction was tested by comparing the English proficiency attained by 46 native Korean or Chinese speakers who had arrived in the United States between the ages of 3 and 39, and who had lived in the United States between 3 and 26 years by the time of testing. These subjects were tested on a wide variety of structures of English grammar, using a grammaticality judgment task. Both correlational and t-test analyses demonstrated a clear and strong advantage for earlier arrivals over the later arrivals. Test performance was linearly related to age of arrival up to puberty; after puberty, performance was low but highly variable and unrelated to age of arrival. This age effect was shown not to be an inadvertent result of differences in amount of experience with English, motivation, self-consciousness, or American identification. The effect also appeared on every grammatical structure tested, although the structures varied markedly in the degree to which they were well mastered by later learners. The results support the conclusion that a critical period for language acquisition extends its effects to second language acquisition. PMID- 2920539 TI - Evaluation of a dental preventive program for Danish chocolate workers. AB - The purpose of the present study was to develop and evaluate a preventive dental program at two Danish chocolate factories. The program was undertaken within the setting of an occupational health service in order to control oral occupational diseases. Eighty-nine persons (80%), 19-61 yr of age, participated in a 2-yr follow-up study. Preventive care was offered to the workers by a dental hygienist. Clinical prophylaxis was given at four visits the first year and two visits the second year. Health education was based on active involvement of the participants and safety committee or safety group members in order to stimulate self-care activities at the factories. The outcome of the program was evaluated by clinical recordings of visible plaque index (VPI), gingival bleeding (GB), calculus index (CI), and DMFS. Data on dental conditions were recorded at baseline, after 12, and after 24 months. Questionnaires were completed by the workers each time in order to obtain data on dental knowledge, attitudes, dental health behavior, social network activities, and perceptions of the process. The results showed improvement in dental health in terms of stepwise reductions in VPI, GB, CI, and DS. For example, mean GB decreased from 36% of the teeth scored at baseline to 9% at 24 months and mean DS decreased from 2.3 to 0.7. Positive developments of dental health behavior were observed. The proportion of workers reporting daily toothbrushing at work increased from 6% to 24% during the program and the proportion of workers using dental floss regularly increased from 24% to 47%. However, the changes in dental knowledge and attitudes were rather diffuse.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2920540 TI - Dental patients' knowledge and beliefs about periodontal disease. AB - The knowledge and beliefs about periodontal disease of 1093 regularly attending patients in 36 North Carolina general dental practices were examined. Patients had a strong positive orientation toward keeping their teeth. Correct information concerning the signs, causes, prevention, and treatment of periodontal disease was widely held. Older patients were more knowledgeable about treatment and signs of periodontal disease, while younger patients expressed more positive beliefs about keeping their teeth for a lifetime. Although patients' knowledge was not perfect, it included few misperceptions that could threaten oral health. Additional education was most needed with respect to the significance of bleeding gums. PMID- 2920541 TI - Reproducibility and overlapping of bitewing radiographs: comparison of Eggen-bite with Kwik-bite. AB - In the present study the reproducibility of horizontal dimensions and of overlappings of two filmholder techniques with aiming devices (Eggen-bite and Kwik-bite) and additionally the number of overlappings on the resulting bitewing radiographs were compared. The overlapping reproducibility was significantly higher with Kwik-bite. The microdensitometric reproducibility demonstrated the same tendency, but the result was not significant. Bitewings carried out by an oral radiologist demonstrated fewer overlappings with Eggen-bite than with Kwik bite, while bitewings carried out by inexperienced students revealed no difference between the methods. Both reproducibility and number of overlappings should be taken into consideration when bitewing filmholder techniques are used in epidemiological and longitudinal studies. PMID- 2920542 TI - Comparison of oral radiographic findings among 35-year-old Oslo citizens in 1973 and 1984. AB - The purpose of the present study was to evaluate a variety of radiographically detectable conditions found on orthopantomograms of 141 individuals as a part of an oral health survey of 35-year-old Oslo citizens, born 1949. Radiographic findings were recorded and compared with those of a similar study made in 1973. The findings revealed a statistically significant reduction in the prevalence of marginal bone loss. The frequencies of endodontically treated teeth and teeth with apical radiolucencies were unchanged. PMID- 2920543 TI - Oral health of Polish children and WHO/FDI goals for the year 2000. AB - Based on available epidemiology data, dating sporadically from 1967 to 1985, of the oral health situation of Polish children and youngsters, the attainment of the first three oral health goals of FDI/WHO for the year 2000 is discussed. It can be assumed that the first oral health goal may be reached by at most only 10% of Polish children. The second oral health goal may be achieved by some 60% of 12 yr-old Polish children. The third oral health goal will be reached by at most 33% of 18-yr-old Polish youngsters. The reasons for these rather pessimistic prognoses are explained. PMID- 2920544 TI - Reassessment of the effect of fluoridation on cost of dental treatment among Scottish schoolchildren. AB - The present study, which is a repeat of a 1980 study, compares the dental treatment needs of 5, 10, and 15-yr-old life-time residents of a fluoridated town (Stranraer) and non-fluoridated town (Annan). Although fluoridation ceased in July 1983, the cost of all dental treatment in 1986 was 57% lower for 5-yr-olds in the fluoride area compared with the non-fluoride one. The corresponding differences in costs for 10- and 15-yr-old groups were 36% and 63%, respectively. Comparison with the 1980 results showed a 21% drop in the cost of all treatment for 5-yr-olds in Annan and a 4% drop in 10-yr-olds. The corresponding comparison for Stranraer 5-yr-olds showed a 43% reduction in the cost of all treatment. The 10-yr-old group in Stranraer showed a 21% increase in the cost of all treatment and a 115% increase in the cost of restorations for caries. The implications of these findings and the possible link with the cessation of water fluoridation are discussed. PMID- 2920545 TI - Dental hygienists' influence on the patients' knowledge, motivation, self-care, and perception of change. AB - The purpose of this study was to assess the success of the dental hygienist in the dental health education of dental patients in general dental practice. Special emphasis was laid on health education in the field of periodontics. The answers on a questionnaire of 159 dental patients who visited a dental hygienist were compared with the answers of 302 dental patients who had never visited a dental hygienist. The comparison was done by means of t-test and regression analysis on specially developed scales with regard to knowledge, motivation, self care, and perception of change. On all scales the dental patients who visited a dental hygienist scored better. This difference remained when social demographic variables and the dentist's influence were taken into account. This indicates that the dental hygienist is successful in the behavioral aspect of her work. PMID- 2920547 TI - A polyepisodic course in bipolar illness: possible clinical relationships. AB - Using archival data, we conducted a systematic study of consecutive admissions of bipolar patients and found that an early age of onset, a subacute onset, a family history of bipolarity, and the administration of electroconvulsive therapy (ECT) during an index episode were individually associated with a polyepisodic course of illness (three to nine or more episodes) during a period of observation which included onset of illness, index admission, and a period of follow-up. The family history of biopolarity which seems to predispose to multiple episodes suggests that what may be transmitted may not necessarily be a bipolar illness but possibly an illness with many episodes, thus increasing the likelihood of occurrence of a manic episode. PMID- 2920546 TI - Clinical picture of snuff dipper's lesion in Swedes. AB - In a survey of oral mucosal lesions in 20,333 individuals, 1,466 individuals with snuff dipper's lesions were found. All but seven of the snuff dippers were men, which gives a prevalence of snuff dipper's lesions of 15.9% in the male population. Four degrees (1-4) of clinical severity of lesions were allotted. There were positive correlations between the severity of the lesion and years with the habit, daily amount of snuff used, time with contact between snuff and the oral mucosa, and, to some extent, with age of the snuff dipper. There were differences between the different brands of snuff as regards the severity of the snuff dipper's lesion produced. PMID- 2920548 TI - The dose-response relationship for memory impairment by anticholinergic drugs. AB - Twelve stabilized chronic schizophrenic outpatients receiving maintenance treatment with fluphenazine decanoate plus anticholinergic antiparkinsonian drugs underwent two challenge sessions receiving, in random sequence and double-blind, injections of either benztropine or glycopyrrolate (a peripherally active anticholinergic agent that penetrates the CNS poorly, used as an active placebo). Performance on free recall testing was significantly worse after benztropine than after glycopyrrolate. It has previously been shown that routine clinical doses of anticholinergic antiparkinsonian drugs impair verbal learning relative to a drug free baseline. Our results suggest that memory impairment continues to further increase as anticholinergic drugs are pushed to the upper limit of the acceptable clinical range. PMID- 2920549 TI - Traumatic stress disorder: diagnostic and clinical issues in former prisoners of war. AB - Examined are a variety of clinical issues in the diagnosis and treatment of Posttraumatic Stress Disorder (PTSD) of former prisoners of war (POWs). Difficulties and complexities in understanding and diagnosing PTSD in former POWs presenting symptomatic complaints associated with this disorder are explored. Data collected on former POWs complaining of PTSD and diagnosed by DSM-III-R criteria revealed Minnesota Multiphasic Personality Inventory (MMPI) and Millon Clinical Multiaxial Inventory (MCMI) clinical profiles appropriate for clinical application. Comparative data between German-held and Japanese-held POWs experiencing PTSD and adjustment-related stressors are discussed. Import on clinical strategies with diagnosed patients suggests both behavioral approaches to treatment and future directions in research. PMID- 2920550 TI - Axis I phenomenology of borderline personality disorder. AB - The Axis I phenomenology of 50 outpatients meeting both Diagnostic Interview for Borderlines (DIB) and DSM-III criteria for Borderline Personality Disorder (BPD), 29 outpatients meeting DSM-III criteria for Antisocial Personality Disorder (APD), and 26 outpatients meeting DSM-III criteria for Dsythymic Disorder as well as DSM-III criteria for some other type of Axis II disorder (dysthymic OPD) was assessed blind to clinical diagnosis using the Structured Clinical Interview for DSM-III (SCID). Borderlines were significantly more likely than antisocial controls to have met DSM-III criteria for an affective disorder, particularly Dysthymic Disorder, and an anxiety disorder. They were also significantly more likely than dysthymic OPD controls but significantly less likely than antisocial controls to have met DSM-III criteria for alcohol abuse/dependence and drug abuse/dependence. The authors conclude that: (1) the link between BPD and unipolar affective disorders is less specific than previously suggested, and (2) there is a link between BPD and impulse disorders that may be of equal, if not greater, importance. PMID- 2920551 TI - Personality and suicidal behavior in depressed patients. AB - The relationship between personality and suicidal behavior was evaluated in 53 patients with primary major depressive disorder. Mean borderline personality scale scores on the Millon Clinical Multiaxial Inventory (MCMI) differed between suicide attempters and non-attempters. The frequency of personality disorder diagnoses, especially borderline personality disorder, was not higher in the suicide attempters. Clinical and theoretical implications of these findings are discussed. PMID- 2920552 TI - A comparison of clinical and self-report diagnoses of DSM-III personality disorders in 552 patients. AB - This report examines the relationship between clinicians' diagnoses of personality disorder and self-report diagnoses of personality disorder obtained from the Personality Diagnostic Questionnaire (PDQ). The results from 552 patients showed general lack of agreement between clinical and self-report diagnoses of DSM-III personality diagnoses. The best agreement obtained was for Borderline Personality Disorder: k = 0.46, and r = .51 for scaled ratings. Possible sources of disagreement including failings of the self-report questionnaire, difficulties in relying upon patients' self-reports, lack of reliability of clinical diagnoses of personality, and possible inherent lack of reliability of several of the DSM-III personality disorders are discussed. PMID- 2920553 TI - A family study of anorexia nervosa and bulimia. AB - A family study is presented that examines the association between eating disorders and affective illness. 307 relatives of 30 eating disorder patients, of 16 patients with major depression, and of 20 normal controls, were interviewed to determine lifetime histories of psychiatric illness. Using logistic regression analyses, the results supported previous findings of a familial association between eating disorders and major depression. However, there was no evidence that clinical features of eating disorder patients (presence of bulimia or major depression) can be used to predict morbid risk. In addition, the results failed to reveal a familial aggregation of either alcoholism or drug abuse in eating disorder families. PMID- 2920554 TI - Development of a graphic psychiatric self-rating scale. AB - This report describes the development of a clinical instrument that is intended to assess general inpatient psychopathology among patients who cannot communicate directly with the clinician, either due to a language barrier or other problems with verbal communication. Reliability and validity of the instrument indicate that it can serve a useful purpose as a self-rating scale that obviates the need for extensive verbal communication. The scale also appears to be sensitive to changes in symptom intensity over time. PMID- 2920555 TI - Focus on Scotland. Taking the high road. Interview by Sue Smith. PMID- 2920556 TI - Focus on Scotland. Over the sea from Skye. Interview by Sue Smith. PMID- 2920557 TI - Home--or home? PMID- 2920558 TI - Community nurse profile. All in a day's work. PMID- 2920559 TI - Crisis on the streets. PMID- 2920560 TI - Career paths for nursing: another step forward. PMID- 2920561 TI - Effects of gastric alkalization on bacterial colonization in critically ill patients. AB - Gastric alkalization of critically ill patients is associated with bacterial and fungal overgrowth in gastric contents. We studied the incidence of gastric colonization and its relation to other infections and antibiotic therapy in 25 critically ill ICU patients. All patients received 12-h NG Mylanta II and 15 received an H2-receptor antagonist. All patients had bacterial colonization of NG contents within 4 days of ICU admission and 10 had Candida colonization within 8 days. There were 70 NG isolates and the same isolates were found in tracheobronchial secretions (n = 46), blood (n = 4), urine (n = 4), and wounds (n = 8). Tracheobronchial colonization was preceded by NG colonization with the same organism in 12 instances (11 patients), was concurrent with NG colonization in 20 instances (14 patients), was followed by NG colonization in 14 instances (11 patients), and had no similar NG isolate in 18 instances (11 patients). NG culture of the same organism preceded four of eight positive blood cultures. In 35 of 70 NG isolates and five of 11 subsequent tracheobronchial isolates, colonization occurred despite concurrent appropriate antibiotics. We conclude that colonization of alkalinized NG contents is universal, is a common source of infection in other areas, and is not prevented by systemic antibiotic therapy. Local antibiotic therapy may be important in controlling this important source of infection. PMID- 2920562 TI - Hypothermia outcome score: development and implications. AB - Multiple rewarming methods have been recommended for the treatment of hypothermia in the ED. Because the hypothermic patient population is heterogenous, a method for stratifying mortality risk when comparing therapies is desired. We used univariable and multivariable statistical analyses to identify variables which discriminated between patient death or survival in the 24 h after arrival in the ED. Prehospital cardiac arrest, a low or absent presenting BP, elevated BUN, and the need for either tracheal intubation or NG tube placement in the ED were found to be significant predictors of patient demise in a large database (n = 428). The likelihood ratio was used to develop and validate an empiric hypothermia outcome score that can be used in future hypothermia treatment studies to account for differences of patient presentation. PMID- 2920563 TI - Correlation of nonlinear mathematical transformation of the normal electrocardiogram with the severity of coronary artery disease. AB - Signal processing was applied to normal ECGs to study whether the results could predict coronary artery disease (CAD) on angiography. ECGs determined to be normal by conventional criteria for 116 white males and 84 white females were subjected to signal processing. The technique applied nonlinear mathematical transformation to a segment of seven ECG leads which were photographically imaged, automatically digitized, normalized for time, and had topographical coordinate transformation using an IBM-XT microcomputer. The resulting curvilinear display on the computer monitor was termed a biopotential coordinate transformation (BCT). Successive superimposition of BCTs from normal ECGs of patients with normal angiograms developed boundaries of a normal template for each lead. Study BCTs were then compared to the normal templates to predict the presence or absence of CAD. Correlation of the BCT results with the severity of CAD for the males resulted in average sensitivities of 80%, 84.4%, and 91.7% for single, double, and triple-vessel CAD, respectively. Similarly, for the females average sensitivities were 59.1%, 73.9%, and 88.9%, respectively. In past studies on the same population, the BCT process detected CAD with average sensitivity of 85.1% and specificity of 81.8% for white males and average sensitivity of 73% and specificity 81% for white females. As such, computerized signal processing of ECGs may provide a noninvasive method for detection of CAD in patients with seemingly normal resting ECGs. The results of this study indicate that the sensitivity of the process increases in direct proportion to the severity of CAD. Further investigation is warranted for process refinement and verification. PMID- 2920564 TI - Whole lung pulmonary angiography in the intensive care unit with two portable chest x-rays. AB - Suspected massive pulmonary embolism requires urgent, accurate diagnosis. We describe a technique for pulmonary angiography in the ICU. Four patients admitted with suspected pulmonary embolism had fulminating cardiorespiratory failure with support requirements precluding transfer. Each patient had a flow-directed pulmonary angiography catheter inserted into the pulmonary artery. In two catheter positions, 25 ml of iopamidol 612 mg/ml was delivered from a portable angiographic injector at a flow of 20 ml/sec. A portable x-ray was taken immediately before completion of syringe excursion. Major central pulmonary emboli were seen in three patients and a negative angiogram was obtained on the fourth. Two of the three positive diagnoses were confirmed at pulmonary embolectomy. The negative diagnosis was confirmed at autopsy. Pulmonary angiography via a flow-directed catheter enabled precise and rapid diagnosis of pulmonary embolism in patients too ill to transfer for formal angiography. PMID- 2920565 TI - Screening for hypoglycemia with plasma in neonatal blood of high hematocrit value. AB - A model utilizing human umbilical cord blood was used to screen for hypoglycemia in a simulated neonatal situation. The aims of the study were to assess the effect of increasing Hct concentration on Dextrostix readings, and to determine whether plasma samples, in contrast to conventional whole blood samples, were acceptable for Dextrostix determinations in selected cases. Dextrostix readings were determined on 65 whole blood samples of varying Hct, and on plasma specimens, 48 of which were paired with whole blood samples. The results were compared with plasma true glucose values. Plasma Dextrostix readings correlated well with true glucose values throughout the entire Hct range (r = .94, slope = 1.16). Whole blood Dextrostix readings, on the other hand, were Hct-dependent and, with increasing Hct values, became falsely low. As a result, a Hct values greater than 70%, whole blood Dextrostix readings were less than 50% of the true glucose value (r = .94, slope = 0.45). Plasma Dextrostix determinations may offer an accurate means of screening for neonatal hypoglycemia in asymptomatic infants with high Hct, pending laboratory glucose results. PMID- 2920566 TI - Transient expectoration of pancreatic fluids in a patient with pancreaticopleural fistula. PMID- 2920567 TI - Oxygen delivery and lactic acidosis. PMID- 2920568 TI - Gaar equation is not a reliable predictor of pulmonary capillary pressure. PMID- 2920570 TI - Dermatology convention digest. Highlights from the annual meeting of the American Academy of Dermatology. PMID- 2920569 TI - Acute benzodiazepine withdrawal syndrome after midazolam infusions in children. PMID- 2920571 TI - Flow-directed pulmonary artery catheterization. Moratorium vs clinical trial. PMID- 2920572 TI - Patient dumping. The physician's dilemma. PMID- 2920573 TI - Pleural and lung cryobiopsies during thoracoscopy. AB - Cryotherapy through rigid bronchoscopy has been used in the past three years in the treatment of endobronchial tumors. We performed pleural and lung cryobiopsies during thoracoscopy. The hemostatic properties and the quality of the histopathologic specimens obtained using this technique offer an innovative approach to the diagnosis of pleural effusion with associated lung disease. PMID- 2920574 TI - Unexpected high prevalence of silent pulmonary embolism in patients with deep venous thrombosis. AB - In patients presenting with clinically suspected deep vein thrombosis, symptomatic pulmonary embolism is rarely apparent. To assess the prevalence of silent pulmonary embolism in outpatients with proven deep vein thrombosis but without symptoms of pulmonary embolism, perfusion ventilation lung scans were performed in 101 consecutive patients at presentation. Fifty-one percent of these patients had a high probability lung scan at the initiation of treatment. In comparison, in patients referred with suspected venous thrombosis, but who on subsequent objective testing did not have venous thrombosis (n = 44), the prevalence of a high probability-scan for pulmonary embolus was only 5 percent. At repeat lung scanning, performed after one week of anticoagulant treatment, complete to partial improvement was observed in 68 percent of the patients with initially abnormal scans. Lung-scan detected asymptomatic pulmonary embolism occurs frequently in patients presenting with symptomatic deep venous thrombosis, and the majority of these emboli showed significant to complete resolution within one week of anticoagulant treatment. PMID- 2920575 TI - Chronic thromboembolic occlusion in the adult can mimic pulmonary artery agenesis. AB - In the first 100 patients operated on for C T-E PH, three were referred with the diagnosis of UPAA having been made elsewhere. We found that many features of these two conditions are so similar that differential diagnosis is very difficult. Shared features may include findings on chest x-ray film, pulmonary angiography, CT scan and MRI studies. Since the two conditions vary substantially with respect to the methods of potential surgical correction, recognition of this possible differential diagnostic dilemma is important. PMID- 2920576 TI - Subclinical effects of cigarette smoking. A five-year follow-up of physiologic comparisons of healthy middle-aged smokers and nonsmokers. AB - Measurements of ventilatory function, lung elastic recoil, diffusing capacity, and distribution of ventilation were obtained on healthy middle-aged cigarette smokers and nonsmokers on two occasions five years apart in order to assess the effects of smoking and the change which may occur over this five-year interval. Subjects were drawn from a randomly selected sample of the population of Tucson, AZ. Exactly the same protocol, methods, and equipment were employed in both studies. Although very few of these healthy subjects had abnormal function, there were significant differences in most indices of function between smokers and nonsmokers. However, we could discern no difference between smokers and nonsmokers in change in function over five years. It appears that, in smokers who remain free of serious respiratory trouble, there are subtle changes which accumulate over the years and which are too gradual to detect over a five-year interval. PMID- 2920577 TI - Patient and family participation in the management of respiratory failure in Duchenne's muscular dystrophy. AB - Mechanical ventilation is now considered a therapeutic option for respiratory failure associated with Duchenne's muscular dystrophy (DMD). Through the monitoring of forced vital capacity and PCO2, prediction of impending respiratory failure is possible. This knowledge allows the patient to choose institution of mechanical ventilation before acute respiratory failure or no intervention and preparation for a natural death. To assist patients and families in this decision making, a special clinic was established. Thirty adolescent boys with DMD were followed up. Eighteen boys reached the end stage of their disease. Three died of cardiac failure. Prediction of respiratory failure was possible in 14 of the remaining 15; 11 of the 15 were able to make educated choices regarding respirator assistance or a natural death. The clinic has shown that in the majority of cases, when properly educated, patients and families can be active participants in life-and-death decisions. PMID- 2920578 TI - Doppler evaluation of changing cardiac dynamics during Cheyne-Stokes respiration. AB - For the purpose of elucidating the mechanisms and/or effects of the cardiovascular changes occurring during Cheyne-Stokes respiration, we utilized Doppler echocardiography to determine intracardiac flow velocity profiles during the changing phases. Left ventricular inflow (LVI) and outflow (LVO) were examined in ten patients, nine with heart failure and one with a cerebrovascular accident. The mean LVI, peak early (E) and late diastolic (A) and LVO velocities were measured at the end of both the hyperpneic and apneic phases. The phasic hemodynamic changes observed during Cheyne-Stokes respiration by Doppler profile could be explained by the development of LV diastolic dysfunction and a decrease in LV stroke volume during the apneic phase of Cheyne-Stokes respiration. Alternatively, an increase in PCO2 during the apneic phase may increase pulmonary vascular resistance lowering preload and stroke volume, whereas during the hyperpneic phase, pulmonary vascular resistance is reduced with resultant increase in left ventricular preload and increase in stroke volume. Both theories are speculative and the precise hemodynamic changes associated with Cheyne-Stokes respiration requires further investigation. PMID- 2920579 TI - The relationship between lung volume and standard scalar ECG parameters in normal subjects. AB - Although the relationship between abnormalities in the ECG and lung volumes has been well described in patients with chronic obstructive lung disease, little is known about this relationship in normal subjects. We investigated this relationship in normal, supine subjects at lung volumes ranging from residual lung volume to total lung capacity. We found that there was a significant right shift in the frontal axis with increasing lung volume. Over the precordium, R wave amplitude decreased mainly at the lateral leads and S wave amplitude increased chiefly at the anterior leads. These results are consistent with a normal vertical shift and clockwise rotation of the heart with increasing lung volume. PMID- 2920580 TI - Threshold pressure training, breathing pattern, and exercise performance in chronic airflow obstruction. AB - The effects of six weeks of threshold pressure inspiratory muscle training (IMT) on inspiratory muscle performance, breathing pattern and exercise performance were studied in eight patients with severe airflow obstruction. The results indicated that IMT improved inspiratory muscle performance but did not affect exercise performance or breathing pattern during maximal exercise. PMID- 2920581 TI - Increase in number of myocardial ischemic episodes following nifedipine administration in two patients. Detection of silent episodes by Holter monitoring and role of heart rate. AB - Out of 34 consecutive patients with angina and treated with nifedipine, two subjects (5.8 percent) showed a significant increase of transient myocardial ischemic episodes during the period of treatment, as assessed by continuous Holter ECG monitoring. In both these patients, a large proportion of ischemic episodes happened to be asymptomatic. A relationship between nifedipine intake, heart rate increase, and number of ischemic episodes was observed. This occasional aggravation of myocardial ischemia could be related to an increase in myocardial oxygen demand medicated through a drug-induced reflex tachycardia. PMID- 2920582 TI - Chemiluminescence and antibody-dependent, cell-mediated cytotoxicity between human alveolar macrophages and peripheral blood monocytes in smokers, nonsmokers, and lung cancer patients. AB - Some evidence suggests a capability of peripheral blood monocytes to destroy tumor cells, while this ability by human alveolar macrophages, the main defense cells in the alveoli, is still debatable. We measured the chemiluminescence and antibody-dependent, cell-mediated cytotoxicity in the PBMs and HAMs of 12 lung cancer patients and 20 healthy subjects; the latter included ten smokers and ten nonsmokers. The PBMs were prepared by using a Ficoll-Hypaque density gradient, then separated by Petri-dish adherence. The HAMs were taken during the bronchoalveolar lavages. The chemiluminescence in the HAMs of smokers was significantly higher than nonsmokers, (p less than 0.05), which did not occur in the PBMs. Chemiluminescence in HAMs from the lung cancer patients was also significantly higher than the smoker control subjects (p less than 0.01). However, the lung cancer patients had significantly lower ADCC activity than the smokers in the control group (4.52 +/- 2.96 vs 8.27 +/- 2.83 percent; p less than 0.05). The chemiluminescence in the PBMs showed no statistical difference between the lung cancer patients and smoker control, but PBMs of the lung cancer patients had significantly lower ADCC activity than the smoker normal control group. The HAMs from lung cancer patients produced more superoxide anion, for an increased chemiluminescence reaction was noted, although ADCC activity was lower than in smokers, ie, HAMs were ineffective in killing tumors. Environmental factors such as cigarette smoking affect HAM's function by causing an increase of superoxide anion production. The chemiluminescence and ADCC activity in the PBMs does not always correspond to the HAMs findings. These results suggest that PBMs can not accurately reflect or predict the HAMs' function in lung diseases. PMID- 2920583 TI - Comparison of PEFR and FEV1 in patients with varying degrees of airway obstruction. Effect of modest altitude. AB - Measurements of FEV1 and PEFR performed on a Jones Pulmonor Spirometer (JPF) were compared with PEFR obtained with a mini-Wright peak flow meter (WPF) in 102 patients. Data were converted to percent predicted. Standard deviations of triplicate measurements were: FEV1, 3.01 percent; JPF, 7.22 percent; and WPF, 5.12 percent. Correlation of best of three measurements was FEV1-JPF r = .758; FEV1-WPF r = .744; and JPF-WPF r = .846. The mean percent predicted of the best of three values of FEV1 was 74.8 percent, JPF 91.4 percent, and WPF 94 percent. These higher values for percent predicted PEFR were obtained throughout the range of FEV1 values. Studies on nine normal volunteers in an atmospheric chamber suggested that higher altitudes may account for higher PEFR values. We conclude that PEFR, measured by either waterless spirometer or mini-Wright peak flow meter, has greater intrasubject variability than FEV1, and it tends to underestimate the degree of pulmonary impairment. PMID- 2920584 TI - A randomized controlled trial of methylprednisolone in the emergency treatment of acute exacerbations of COPD. AB - We conducted a randomized, controlled double-blind study to determine whether intravenous administration of methylprednisolone early in the therapy for acute exacerbations of COPD would improve pulmonary function in the Emergency Department and reduce the need for hospitalization. Ninety-six patients completed the study. All were at least 50 years of age and had no history of asthma. Patients received aminophylline and hourly administration of aerosolized isoetharine. Methylprednisolone (100 mg) or physiologic saline solution was given within one-half hour of arrival in the Emergency Department. Spirometry was performed initially and after the third and fifth aerosol treatments. We found no greater improvement in FEV1 in the group receiving the steroid (37 percent) than in the control group (43 percent; NS). There was also no difference in the rate of hospitalization (33 percent in the steroid-treated group vs 30 percent in the control group; NS). We conclude that early administration of methylprednisolone does not affect the emergency phase of treatment for acute exacerbations of COPD. PMID- 2920585 TI - Dexamethasone as prophylaxis for acute mountain sickness. Effect of dose level. AB - Rapid exposure of unacclimatized persons to high altitude causes the syndrome acute mountain sickness (AMS). Prophylactic treatment with frequent high doses of dexamethasone has been shown to prevent AMS. To determine whether lower, less frequent doses were effective in preventing AMS, 28 men between the ages of 18 and 32 were exposed to a simulated altitude of 4,570 m for 45 h in a hypobaric chamber on two occasions while taking one of three doses of dexamethasone (4 mg, 1 mg, or .25 mg every 12 h) or a placebo in a double-blind, crossover design. The 4-mg dose of dexamethasone reduced the incidence of AMS symptoms compared with placebo and the other dose levels. Dexamethasone did not alter fluid balance or plasma volume changes, but treatment with 1 mg and 4 mg suppressed cortisol secretion. There was no evidence of adrenal cortical suppression after treatment with dexamethasone or placebo 48 h after discontinuing altitude exposure and drug treatment. The results indicate that 4 mg of dexamethasone twice daily is an effective prophylactic treatment for AMS, while lower doses are relatively ineffective. PMID- 2920586 TI - Phenotype of blood monocytes and alveolar macrophages in interstitial lung disease. AB - The immunologic phenotype of the monocyte-macrophage cell populations in bronchoalveolar lavage (BAL) fluid and monocytes in peripheral blood (PB) were studied in 20 patients with sarcoidosis, 18 with idiopathic pulmonary fibrosis (IPF), seven with extrinsic allergic alveolitis (EAA), and 12 healthy volunteers. There were no significant differences in expression of the immunologic markers CD13(My7), CD14(My4), and Monocyte-2 on blood monocytes between the patient groups and healthy volunteers, but there were marked differences between groups in the expression of the three markers on BAL macrophages. The percentage of Monocyte-2+ macrophages was increased in BAL in subjects with sarcoidosis, EAA, and IPF compared with healthy volunteers, greatest in EAA. This increase is probably due to increased recruitment of blood monocytes into alveoli, since the cells had a monocytic morphology on phase contrast microscopy (in normal subjects the majority of blood monocytes, but few alveolar macrophages, express the Monocyte-2 antigen). Patients with IPF had a significantly lower percentage of CD13(My7)+ macrophages in BAL than the other three groups. Compared with IPF patients and healthy volunteers, patients with EAA had a significantly higher percentage of CD14(My4)+ macrophages, whereas in sarcoidosis patients the numbers were reduced. These observations suggest an increased influx of blood monocytes into the alveoli in interstitial lung disorders. Phenotypic differences were found between the BAL macrophage populations of the various interstitial diseases. These differences in alveolar macrophage phenotype may be due to local factors, depending on the type of inflammation. PMID- 2920587 TI - Effect of radiation therapy on bronchial obstruction due to bronchogenic carcinoma. AB - We evaluated the effect of radiation therapy in 57 patients with obstruction of a large bronchus with NSCC. Response with aeration of the atelectatic lung was seen in 12 patients (21 percent). Three patients (5 percent) showed partial response with persistent partial atelectasis, and nine patients (16 percent) showed good response with complete aeration of the atelectatic lung. In these patients the response appeared to be related to the dose of radiation. All of the patients who responded received more than 50 Gy. The difference in the response rate related to the dose of radiation was statistically significant (p less than 0.05). The rates were similar with all histologic types of NSCC. Regardless of the clinical response observed, bronchoscopy performed two to four months after completion of radiation therapy in 14 patients revealed persistent endobronchial tumor. There was no significant relationship between the persistence of endobronchial tumor, the dose of radiation therapy, and the tumor's histologic type. Of the 12 patients with radiographic improvement in atelectasis, fibrotic changes developed in four (33 percent) patients and pneumonitis in two (17 percent). Progression of disease with distant metastases occurred in 58 percent (seven) of the 12 patients who showed a clinical response of their bronchial obstruction. The median time to survival was nearly identical in responders and nonresponders. PMID- 2920588 TI - Chronic simple bronchitis in pigeon fanciers. Relationship of cough with expectoration to avian exposure and pigeon breeders' disease. AB - The prevalence of chronic bronchitis and its relationship to antigenic exposure was studied in a population of pigeon fanciers. Two hundred and eighty seven fanciers completed a questionnaire regarding symptoms and circumstances of avian exposure and had IgG antibody to pigeon gammaglobulin measured by an enzyme linked immunosorbent assay. Chronic bronchitis occurred in 26.2 percent of nonsmoking fanciers and increased in prevalence as antibody levels rose (p less than 0.001). Although significantly more common (p less than 0.005) in the 85 (29.6 percent) fanciers who also had typical delayed symptoms of pigeon breeders' disease (PBD), chronic bronchitis was the only manifestation of the disease in 24 (8.4 percent) of the population surveyed. Chronic bronchitis was not related to the intensity or duration of avian exposure suggesting that host factors are more important in its pathogenesis. Chronic bronchitis must be considered to be an integral part of the clinical spectrum of PBD. PMID- 2920589 TI - A possible association of rheumatoid arthritis and sarcoidosis. AB - There are eight previous reports of sarcoidosis developing in patients with rheumatoid arthritis. Reported here are two patients with rheumatoid arthritis who developed sarcoidosis. Both patients have HLA antigen DR4 and Sjogren's syndrome. Only stage II chest roentgenogram abnormalities previously have been described in patients with rheumatoid arthritis who developed sarcoidosis. This report demonstrates that these patients may present with stage III sarcoidosis. The prevalence of sarcoidosis in this clinic population is two per 263 as compared with 20 to 80 per 100,000 in the general population. This may indicate a previously unappreciated increased prevalence of sarcoidosis in patients with rheumatoid arthritis. PMID- 2920590 TI - Continuous monitoring of mixed venous oxygen saturation in patients with acute myocardial infarction. AB - Continuous measurement of mixed venous oxygen saturation (SvO2) has been suggested as an adjunct in monitoring critically ill patients. We evaluated SvO2 monitoring in 24 patients suffering from complicated myocardial infarctions. Cardiac output and arterial lactate levels were measured when there were persistent 5 percent changes in SvO2, and otherwise, every 12 hours or as indicated clinically. Increases in SvO2 by 5 and 10 percent corresponded with an increase in cardiac index in 78.5 percent and 75 percent of measurements, respectively. Decreases in SvO2 by 5 and 10 percent corresponded with decreases in cardiac index in 45.5 percent and 61 percent of measurements. Twenty percent changes in cardiac index showed dissimilar directional changes with SvO2 in 62 percent of cases. Arterial blood lactate levels correlated poorly with SvO2. Survivors had significantly higher mean SvO2 and cardiac indices than nonsurvivors (p less than 0.01). The clinical management of patients with myocardial infarction may not be altered in view of the limitations of SvO2 in reflecting tissue hypoxia. We conclude that continuous monitoring of SvO2 may not be a sensitive measure of cardiac output after acute myocardial infarction. PMID- 2920591 TI - Inotropic response to digoxin and dopamine in patients with severe sepsis, cardiac failure, and systemic hypoperfusion. AB - We studied the inotropic response to dopamine and digoxin in 20 patients with severe sepsis and left ventricular failure. Left ventricular failure was defined as a left ventricular stroke work index less than or equal to 40 g.m/m2 at a pulmonary artery wedge pressure greater than or equal to 15 mm Hg. Hemodynamic assessment was obtained before and following administration of digoxin 10 micrograms/kg IV or dopamine, 5 to 12 micrograms/kg/min IV. Patients treated with digoxin demonstrated a significant increase in LVSWI. The LVSWI increased 13 +/- 10 percent in the dopamine-treated patients compared with 74 +/- 16 percent in the digoxin patients (p less than 0.02). We conclude that digoxin exhibited significant inotropic activity in patients with sepsis. PMID- 2920592 TI - Invasive hemodynamic monitoring in the United Kingdom. Enough or too little? AB - In response to a questionnaire regarding use of invasive hemodynamic monitoring techniques in the United Kingdom, 211 replies were received from 276 hospitals (76.4 percent). Over one fifth of Intensive Care or combined Intensive/Coronary Care Units did not use pulmonary artery catheters (PAC); of those that did, two thirds used no more than two/month, and only two units used more than ten/month. Nearly a quarter did not possess a cardiac output computer. Only 18 complications occurring in the preceding year were reported, which suggests underrecognition. Clinical indications and lack of expertise were the main reasons proferred for limited use; however, cost (which was generally underestimated) and clinical value also were mentioned. The majority of CCUs did not use PACs, and only 10 percent used more than two/month. Only 10 percent of hospitals have used them perioperatively and most cardiothoracic units used no more than two PACs/month. In view of the large difference in numbers used between the United Kingdom and the United States, a large-scale study is warranted to determine the actual value of PACs in reducing mortality and morbidity. PMID- 2920593 TI - Ventilation-perfusion imaging in evaluating regional lung function in nonpenetrating injury to the chest. AB - The extent of chest wall and lung injury after nonpenetrating injury to the chest (NIC) determine how aggressive and invasive management modalities should be. We investigated the value of ventilation (133Xe) and perfusion (99mTc) studies as indicators of extent of lung injury in 28 patients with moderate to severe unilateral NIC. The ventilation-perfusion (V/Q) abnormalities were compared with parameters conventionally used to evaluate NIC. All studies were carried out within 24 h of NIC and repeated 24 h later. Ventilation (p less than 0.001) and perfusion (p less than 0.01) abnormalities were more extensive soon after NIC than suggested by chest roentgenograms. Chest x-ray film changes lagged behind V/Q changes on admission and also after 24 h. The extent of ventilation, perfusion, and chest x-ray film abnormalities on admission were all predictors of increased morbidity. V/Q studies may be useful to define the extent as well as the changes in regional lung function following NIC. PMID- 2920594 TI - Automaticity of the SN and A-V junctional tissue before and after chemical denervation in the dog. AB - Automaticity of SN and A-V junctional tissue was studied in 40 dogs in which a stable junctional rhythm was obtained following thermal ablation of the SN and sulcus terminalis. Atrial overdrive pacing studies were performed both before and after chemical denervation of the heart. Control sinus cycle and junctional CL were 438 +/- 13 ms and 751 +/- 23 ms, respectively. Chemical denervation resulted in significant prolongation of both junctional CL and maximal corrected junctional recovery time; junctional rate was down to 46 percent of the sinus rate observed before suppression of SN activity. Neither sinus CL nor maximal corrected SN recovery time changed significantly after administration of drugs. The basal autonomic nervous system has a relatively greater influence on the junctional pacemaker than on the normal SN in the dog and, when SN was suppressed, chemical denervation prolonged the junctional CL by 23 percent and junctional recovery time by 63 percent. PMID- 2920595 TI - Removal of bronchial secretions by two-phase gas-liquid transport. AB - Net outward wave motion of secretions from airways by two-phase gas-liquid transport is favored by higher airflow during expiration than inspiration. This can be accomplished by IRV in which the controlled mode of mechanical ventilation is adjusted such that the inspiratory cycle is prolonged and the expiratory phase is shortened. Studies were done on six anesthetized, nasally intubated sheep. Simulated mucus was instilled into the bronchi at 15-min intervals during I-E ratio of 1:2.7, 1.9:1, and 3:1. The IRV modes of 1.9:1 and 3:1 promoted transport of simulated mucus outward. Neither systemic blood pressure nor cardiac output were altered by IRV. Thus, IRV might be useful in the management of excessive bronchial secretions in mechanically ventilated patients. However, clinical trials of IRV should take into account its potential for producing adverse hemodynamic effects and barotrauma in patients with compromised cardiac function due to auto-PEEP attendant with its usage. PMID- 2920596 TI - The man who loved drunken crabs. A case of pulmonary paragonimiasis. PMID- 2920597 TI - Management for interstitial lung disease. State of the art. AB - A survey of 109 pulmonary physicians representing both private practice and academic medicine was conducted to learn their practice of management and treatment of interstitial lung disease. Of the 109, 25 (23 percent) responded. Twenty-two of 23 routinely obtain tissue diagnosis. The routine method was transbronchial biopsy by 15 physicians vs open lung biopsy by seven. Few (n = 5) use BAL cell analysis. The majority of clinicians used two to four criteria to initiate therapy. Physiology laboratory data were the predominant criteria used by the majority of physicians and also were most commonly used to monitor a patient's course over time. Prednisone was the drug of choice for therapy. Immunosuppressive therapy was not used until failure of steroid therapy was observed. There was little consistency in the diagnostic procedures applied, criteria for the decision to treat, the drugs used to treat, or methods for monitoring. PMID- 2920598 TI - Superimposed high frequency ventilation with conventional mechanical ventilation. AB - A 73-year-old man with ARDS-multiple organ failure due to Chlamydia psittaci, was successively supported with conventional respiratory techniques. After 48 hours of no clinical improvement, HFV was superimposed to CMV in order to combine the advantages of each one. Since improvement has been seen in all ventilatory parameters, this method is suggested as another mode of ventilation for patients with refractory hypoxia and hypercarbia who do not respond to conventional respiratory care. PMID- 2920599 TI - Sudden death as the initial manifestation of diffuse pleural mesothelioma. AB - Malignant mesotheliomas are generally considered pathognomonic of asbestos exposure. The prognosis of mesothelioma varies with clinical staging of the disease. The overall survival of patients from the time of diagnosis is six to 16 months. Although patients with malignant mesotheliomas often have nonspecific symptoms and signs, occult diffuse pleural mesothelioma is uncommon, and one that occurs in a patient with no evidence of asbestos exposure must be exceedingly rare. Sudden death as the initial manifestation of pleural mesothelioma, to our knowledge, has not been previously reported in the literature. One such unusual case is documented here. PMID- 2920600 TI - Stump neuroma masquerading as recurrent malignancy on chest roentgenogram. AB - An amputation neuroma is a nerve's attempt at repair following amputation. While many are asymptomatic, some present as a painful mass. We describe a patient who, following a forequarter amputation for sarcoma, developed a stump neuroma that was unusual because it was first discovered on a routine chest roentgenogram. PMID- 2920601 TI - Postobstruction pulmonary edema. AB - Several occurrences of pulmonary edema following relief of acute upper airway obstruction have been reported. The edema is associated with normal cardiac filling pressures and responds promptly to conservative therapy. Its origin may be attributed to the cardiopulmonary effects of the vigorous inspiratory effort that the spontaneously breathing patient generates to overcome respiratory obstruction (the Muller maneuver). A patient with postobstruction pulmonary edema complicated by hypovolemia and myocardial infarction is described. Prompt invasive hemodynamic monitoring in selected high-risk patients is suggested. PMID- 2920602 TI - Head-up tilt table evaluation in a trained athlete with recurrent vaso-vagal syncope. AB - A 27-year-old trained athlete with recurrent syncope of suspected vaso-vagal origin was evaluated. A 60 degrees head-up tilt table test reproducibly triggered the patient's spontaneous symptoms and allowed the investigation of different modalities of therapy (medical and pacing) in preventing syncopal episodes. The head-up tilt table test may be a useful tool in the evaluation of syncope of vaso vagal origin, helping to determine the initial precipitating vagal event and the effect of therapy. PMID- 2920603 TI - Pulmonary infiltration with blood eosinophilia after scorpion sting. AB - A 30-year-old man developed bilateral pulmonary infiltrates with blood eosinophilia after receiving a scorpion sting. A short course of corticosteroids resulted in rapid improvement. The PIE syndrome after scorpiasis has not, to our knowledge, been described previously. PMID- 2920604 TI - Recurrent bronchial carcinoid tumor. AB - Bronchial carcinoid tumors are considered to be of low grade malignancy, and if completely resected, to be cured. A patient with resection of a bronchial carcinoid presented 18 years later with superior vena caval obstruction, and carcinoid syndrome due to a recurrence. There was an excellent response to radiation. PMID- 2920605 TI - Depressed central respiratory drive causing weaning failure. Its reversal with doxapram. AB - A patient failed to wean from mechanical ventilation. Her problem was unique in that she had a depressed central drive to breathe manifested by hypopnea when removed from the ventilator. After excluding the known problems that impair successful weaning, we empirically administered three separate infusions of doxapram, a respiratory stimulant. These infusions produced a dramatic improvement in spontaneous ventilation and led to successful weaning and hospital discharge. PMID- 2920606 TI - Removal of broken fragment of biopsy forceps with magnetic extractor. AB - Transbronchial lung biopsy performed on a 51-year-old woman for the evaluation of nodular densities with cavities in the bilateral apical areas was complicated by the breakage of the biopsy forceps. The broken fragment of the forceps was successfully retrieved by use of the magnetic extractor through a fiberoptic bronchoscope under fluoroscopic guidance. PMID- 2920608 TI - Myocardial bridging of a coronary artery--a not-so-benign anomaly. PMID- 2920607 TI - Elicitation of myocardial ischemia by nifedipine in a case of coronary artery fistula. AB - A 63-year-old woman had chest pain that worsened when nifedipine was given. She was found to have a right coronary-to-thorax angioma/fistula. Acute nifedipine administration elicited precordial symptoms, associated with ischemic changes in the inferior ECG leads and an obvious vasodilatation of the fistulous tract, suggesting that a nifedipine-induced "steal" phenomenon might be responsible for the paradoxic clinical response. PMID- 2920609 TI - Diagnostic value of serum to pleural fluid zinc ratios in pleural effusions. PMID- 2920610 TI - Legionella pneumonia and AIDS. PMID- 2920611 TI - Bronchoalveolar T-lymphocytosis in HTLV-1-associated myelopathy. PMID- 2920612 TI - Bronchoscopic aspect of pulmonary aspergilloma. PMID- 2920613 TI - Leaking endotracheal tube. PMID- 2920614 TI - Pulmonary function tests in AIDS. PMID- 2920615 TI - [Current aspects of a new staging classification of colorectal cancer and its clinical consequences]. PMID- 2920616 TI - [Current aspects of a new staging classification of bronchial cancer and its clinical consequences]. PMID- 2920617 TI - [Current aspects of a new staging classification of pancreatic cancer and its clinical consequences]. PMID- 2920618 TI - [Long-term laryngoscopic follow-up in vocal cord paralysis following struma surgery]. AB - Of 525 patients 17 (3.2%) showed a laryngoscopically established palsy of the recurrent laryngeal nerve after surgery due to goiter. A laryngoscopic follow-up of all these patients, performed at least one year after the operation, revealed that 76.5% of the recurrent nerve palsies were temporary and 23.5% were permanent. Danger of permanent palsy increased in the sequence--uncomplicated nodular goiter--struma maligna--recurrent goiter. The outcome of long-term follow up showed a palsy rate of 0.8%, which was much lower than the corresponding rate reported by short-term control (p = 0.005). Therefore laryngoscopic long-term follow-up in cases of postoperative abnormal laryngoscopic function should be a standard part of follow-up in thyroid gland surgery. PMID- 2920619 TI - [Synchronous occurrence of neoplasias of the thyroid gland and hyperthyroid nodular struma in an endemic area]. AB - The simultaneous occurrence of hyperthyroidism and differentiated carcinoma of the thyroid gland is more frequent than previously assumed. In our endemic goiter region 16.5% of patients with thyroid carcinoma have hyperthyroidism and 1.8% of patients with hyperthyroidism have a thyroid carcinoma. The tumors are predominantly located in autonomous adenomas but are also found in cold nodules. Not only scintigraphically cold nodules but also warm and hot nodules must be suspected of malignancy. Consistent preoperative cytodiagnosis of all goiter nodules, including hot nodules, is therefore recommended. Surgical treatment of toxic multi-nodular goiters should be considered more often. PMID- 2920620 TI - [Identification of the recurrent laryngeal nerve in thyroid gland surgery--a status determination]. AB - The recurrent laryngeal nerve palsy is the most important complication in thyroid surgery. It seems to be possible to reduce the rate of palsies by consequently identifying the recurrent laryngeal nerve. A comparison of statistics out of the literature with and without identification of the recurrent laryngeal nerve shows this. A follow-up of our patients of the years 1980-1982 (1312 operations) confirms this finding. PMID- 2920621 TI - [Systematic assessment of postoperative complications. A form of personal quality control]. AB - A quality control program for the surveillance of surgical complications is described which includes all persons working at a surgical unit. The house surgeon when writing his letter for the general practitioner after the patient is demissed uses a special form for postoperative complications. Ten well defined types of complications, e.g. haematoma, fistula, abscess, pneumonia are recorded. Another surgeon responsible for the control program gathers weekly all forms presenting the results monthly at an audit to all surgeons of the unit. Here results are discussed in detail. Each surgeon gets his own complication profile monthly. Every three months the results of surveillance program are presented to all staff members including nurses, so that cooperative actions to reduce the complication rate can be taken. From January 1, 1985 to June 30, 1987, 2597 operations were performed, 213 patients (8.2%) suffered postoperative complications especially after surgery of the colon and rectum (28%), cholecystectomy (26%) and hernia repair (18%). Comparing three time periods (1985, 86, 87) no significant amelioration of complication rates were found. But factors influencing complications like very high age of patients, seriousness of the disease, and diabetes were not evenly distributed in all three samples. Therefore it might be impossible to lower the complication rate since those factors can't be influenced by better preparation for and better performing of surgery. PMID- 2920622 TI - [Microvascular re-anastomosis of the testis in management of recurrent inguinal hernia]. PMID- 2920623 TI - [The new TNM classification and its effect on surgical treatment of stomach cancer]. PMID- 2920624 TI - Colorectal trauma. AB - Surgical treatment of colon and rectal trauma continues to challenge physicians. Injuries to a colon or rectum filled with feces results in subsequent peritoneal contamination which will lead to severe septic complications unless dealt with promptly and correctly. The authors have reviewed the records of 242 patients with colon and rectal trauma operated on at the Cook County Trauma Unit from July 1, 1973 to December 31, 1983, to evaluate treatment results. The mechanism of trauma was penetrating in 233 of 242 patients. Most, if not all, colonic lesions were treated with either exteriorization, resection and no anastomosis, or closure and proximal colostomy. Mortality related to colonic injury was 2.5 percent. Morbidity related to colonic injury included wound infection, 6.3 percent; abscess, 2.5 percent; other, 3.3 percent. Despite the severity of the trauma, adherence to conservative principles of "no anastomosis" in the overwhelming majority of cases has resulted in low morbidity and mortality. PMID- 2920625 TI - Defecometry. A new method for determining the parameters of rectal evacuation. AB - The parameters of defecation, i.e., maximum rectal pressure increase during straining, duration of effective evacuation, and the work performed to evacuate a simulated stool, can be quantified by defecometry, a new method to evaluate the defecation act. Simultaneous anal pressure records demonstrate the nature of the sphincter activity during simulated defecation. The test was performed on 19 patients with constipation and on 14 controls. Five patients could not evacuate the simulated stool, while five others could, but more laboriously than the remaining nine patients whose defecation was comparable with the controls. Laborious defecation is characterized by longer duration and more performed work during evacuation. Every patient with difficult or ineffective evacuation had sphincter contraction during defecation, whereas this phenomenon was not observed in patients with normal defecation. Defecometry permits more adequate identification and characterization of the outlet-obstruction-type constipated patients than the simple balloon expulsion test and the analysis of sphincter activity during straining with empty rectum in lateral decubitus. Early diagnosis and treatment of patients with outlet obstruction is important to avoid late neuromuscular damage to the pelvic floor. PMID- 2920626 TI - A new balloon-retaining test for evaluation of anorectal function in incontinent patients. AB - The balloon-retaining test consists of progressive filling of a compliant intrarectal balloon in a patient in the sitting position. The pressure inside the balloon is monitored and the patient is asked to retain the balloon as long as possible and to report first, constant, and maximal tolerable sensation levels. A balloon is used to simulate semisolid and solid stool. This test is a more realistic approach to the evaluation of fecal continence than the rectal saline infusion test and anal manometry. The test evaluates the rectal reservoir function, sensation, and sphincter competence simultaneously; however, the real rectal distensibility and compliance must be determined by compliance measurement until the maximal tolerable level for patients in a reclining position is reached. This test also permits objective evaluation of the effect of different treatments in incontinent patients. PMID- 2920627 TI - Recurrent typhlitis. A disease resulting from aggressive chemotherapy. AB - Neutropenic typhlitis is a frequently fatal disease most commonly reported in leukemics. The authors have treated eight such patients over the last 18 months. All patients had abdominal pain and sepsis during chemotherapy-induced neutropenia. CT scanning was diagnostic in six patients thought to have typhlitis. Two patients were not diagnosed before exploratory laparotomy. The authors have found nonoperative treatment highly effective in patients who do not manifest signs of peritonitis, perforation, gastrointestinal hemorrhage, or clinical deterioration. Recurrent typhlitis was frequent after conservative therapy (recurrence rate, 67 percent), however. One patient underwent an elective right hemicolectomy after a second episode, and typhlitis did not recur despite neutropenia associated with a subsequent course of chemotherapy. It is concluded that successful treatment of this disease hinges on: 1) early diagnosis provided by a high index of suspicion and the use of CT scanning, 2) nonoperative treatment for uncomplicated cases, and 3) elective right hemicolectomy to prevent recurrence. PMID- 2920628 TI - Prognostic staging of extraperitoneal rectal cancer. AB - In 375 patients who had curative resection for cancer of the rectum below the peritoneal reflection, prognosis was evaluated according to four currently used staging systems, i.e., Dukes' system, the modified TNM system described by the American Joint Committee for Cancer Staging, The Australian Clinicopathological Staging System, and The Astler-Coller Staging System. Dukes' Staging System, which originally was described for use in rectal cancer, gives as good a prognostic separation as any of the other staging systems, some of which include serosal involvement as a staging criteria, which cannot be used for cancer of the extraperitoneal part of the rectum. It is furthermore demonstrated that an important prognostic separation can be obtained by dividing the B group of Dukes' Staging System into tumors that reach the surface of the muscularis propria and those with demonstrable invasion of extrarectal structures, the latter having as bad a prognosis as Dukes' C tumors. PMID- 2920629 TI - Intraoperative colonic irrigation with povidone iodine. An effective method of wound sepsis prevention. AB - In the ten-year period between 1975 and 1986, 367 patients underwent colonic resection with subsequent anastomosis using intraoperative colonic irrigation with 10 percent povidone iodine. One hundred thirty three patients underwent resection of the right or transverse colon, whereas 233 patients had left hemicolectomy with low anterior anastomosis or reanatomosis. Twenty individuals underwent emergency resection for perforation and temporary end colostomy. Nineteen of these patients returned for definitive reanastomosis as part of a two stage procedure. The rate of wound infection, and/or intra-abdominal abscess formation was retrospectively reviewed and found to be completely nonexistent in these patients. This study examines the various techniques used to reduce the rate of wound infection after colonic surgery and addresses the concept of intraoperative povidone iodine irrigation. PMID- 2920630 TI - Pelvic drainage after anterior resection of the rectum. AB - Thirty patients undergoing anterior resection of the rectum were randomized for postoperative drainage with either corrugated (N = 14) or corrugated plus Shirley sump drain (N = 16). Drainage volume per 24 hours was measured, and volume of residual pelvic fluid collection estimated by CT scan on the seventh postoperative day. A mean of 591.9 +/- 415.2 ml of fluid drained during the first seven postoperative days. There was a significant (P less than 0.01) increase in 24 hour drainage volume between the fourth and sixth postoperative days. There was no significant difference in drainage volumes between the two drainage methods. Residual pelvic fluid collection (median volume, 16 ml) was detected in 80 percent of patients at one week after operation. While this was larger (24 ml median) for the corrugated only group compared with the corrugated plus sump drain group (11.5 ml median), the difference was not significant. Fluid loss during the first postoperative week (616.6 +/- 424.2 ml) was significantly (P less than 0.05) less when the anastomosis was situated higher than 12 cm (294 +/- 192 ml) compared with 6 to 12 cm from the anal margin (496 +/- 210 ml), or after coloanal anastomosis (1077 +/- 432 ml). Residual pelvic fluid collection was larger after coloanal anastomosis (median, 33 ml; range, 1.5 to 90 ml) compared with 6 to 12 cm (median, 11 ml; range, 0-124 ml) or higher than 12 cm (median 9 ml; range, 0 to 16 ml) from the anal margin, but the difference was not significant. Drainage after anterior resection is important because large volumes of serosanguineous fluid collect, especially after resection of low tumors. Neither of the drainage methods tested in this study prevented persisting pelvic fluid collection at the seventh postoperative day. PMID- 2920631 TI - Melanosis coli. Prevalence, distribution, and histologic features in 200 consecutive autopsies at Kuopio University Central Hospital. AB - The occurrence of large-bowel melanosis was evaluated by microscopy in 200 large bowels at autopsy. Melanin was seen as yellow-brown pigment in the macrophages of the lamina propria. The pigment stained with diastase-alcian blue PAS, Fontana, and iron stains. One hundred nineteen of 200 (59.5 percent) bowels showed melanosis, which was equally common in both sexes. Usually more than one segment was involved (most commonly, four segments). Melanosis was common in the proximal part of the colon, but much rarer in distal parts (sigmoid and rectum). Affected segments were successive; negative segments between positive ones were exceptional. If the rectum was affected, all five proximal segments were affected in 11 of 12 cases. The intensity of melanosis was directly related to the number of segments involved. In the oral part of the colon, affected males had a higher intensity of melanosis than affected women, but about the same intensity in the sigmoid and rectum. The fraction of patients with melanosis increased with age. Of men and women in the age group of 20 to 54 years, 32 and 44 percent were affected, and above the age of 75 years, 76 and 67 percent, respectively. PMID- 2920632 TI - Mucinous cystadenocarcinoma of the colon. Report of a case. AB - A rare case of mucinous cystadenocarcinoma arising in the sigmoid colon, found accidentally during an operation for cholecystolithiasis, is reported. The tumor was located 40 cm from the anal verge, and had two histologic variations consisting of a large distended cystic lesion and branching cystic channels with papillary proliferation of the epithelium. Serial sections revealed the existence of a luminal communication between the two lesions. The tumor tissue was seen mainly in the muscularis propria with no mucosal involvement. The papillary portion had a highly differentiated appearance, giving rise to considerable difficulty in determining whether it was benign or malignant. In a localized area, however, the tumor invaded into the subserosa and showed distinctive atypical changes. The tumor cells showed intense reactivity for carcinoembryonic antigen. This mucinous cystadenocarcinoma was considered to be originated from an enterogenous cyst, a possible derivative of duplication of the colon. The differential diagnosis concerning this rare tumor is also discussed. PMID- 2920633 TI - Adenocarcinoma developing in a rectosigmoid conduit used for urinary diversion. Report of a case. AB - Adenocarcinoma of the colon developing at or about the sites of ureterosigmoid anastomoses for urinary diversion has been documented in the literature. A case report is presented that illustrates that a carcinoma can develop in a large bowel urinary conduit not exposed to the fecal stream. Colonic bladders are being used with increasing frequency, making observation for this delayed complication necessary. How this neoplastic transformation might occur is discussed. Suggestions for the management of this problem and guidelines for follow-up are also presented. PMID- 2920634 TI - Perianal Bowen's disease associated with Crohn's colitis. Report of a case. AB - A 24-year-old woman with a two-year history of inflammatory bowel disease, with no anal or perineal involvement, underwent a proctocolectomy and ileostomy. Pathologic evaluation of the specimen revealed Crohn's colitis and unsuspected perianal Bowen's disease. The patient is free of Crohn's and Bowen's disease 6.5 years later. The association of perianal Bowen's disease with Crohn's colitis is discussed. PMID- 2920635 TI - Congratulations on "Current Status". PMID- 2920636 TI - Patient care guidelines. PMID- 2920637 TI - Statement on outpatient percutaneous liver biopsy. AB - This document represents a consensus statement dealing with optimum patient care in a significant clinical area. The statement has been prepared by the Patient Care Committee of the American Gastroenterological Association with the advice of other experts and with peer review. As with all such guidelines, this should be interpreted in a nondogmatic manner, so as not to exclude other therapies or opinions in any particular situation. Based on present knowledge, limited at times, future modifications or other changes in this statement may be necessary. PMID- 2920638 TI - Perforation of esophagus after endoscopic variceal sclerotherapy. Incidence and clues to pathogenesis. AB - To determine the true incidence of endoscopic variceal sclerotherapy (EVS) related esophageal perforation, a retrospective analysis of 900 EVS procedures using sodium tetradecyl sulfate performed on 170 patients during a five-year period (1980-1985) was carried out. Autopsy data of all patients who received EVS and who died (32 patients, 100%) during this period were available to confirm the diagnosis of perforation. Esophageal perforation was confirmed in 5 (2.9%) and was seen in patients with advanced alcoholic liver disease. Importantly, most patients did not manifest features of an esophageal leak, but presented instead as a deterioration in condition and died after a mean (+/- SD) 14 +/- 5.2 days. Analysis of the clinical and EVS data reveals that the risk of developing perforation is high when EVS is performed during active bleeding. The extravariceal location of sclerosant and microabscesses may be important predisposing factors. In our experience large-dose injection, deep ulceration, and balloon tamponade are less likely predisposing factors of this complication. PMID- 2920639 TI - Significant DQw1 association in achalasia. AB - Achalasia is a neuromuscular disorder of the esophagus with unknown etiology. There have been suggestions that this disorder is immunologically mediated. To examine this possibility, HLA phenotyping was prospectively performed on 40 patients with documented achalasia (24 Caucasian, 16 blacks). Results showed a positive association for the class II HLA antigen, DQw1, with 83% of Caucasians (P less than 0.02) and 86% of blacks having the antigen (NS). The relative risk for developing achalasia with the presence of DQw1 was 4.2 in Caucasians and 3.6 in blacks. A negative correlation for the DRw53 antigen was noted in Caucasian patients with a relative risk of 0.23. These results indicate an immunogenetic association for achalasia and provide insight into the pathogenesis of this disorder. PMID- 2920641 TI - Effect of low extracellular calcium on gallbladder contraction in vitro. AB - Increases in intracellular calcium ion mediate smooth muscle contraction, but the requirement for extracellular calcium availability during this process is unclear. We studied the intact guinea pig gallbladder in an organ bath to define the effect of low bath calcium on contractile responses to varying doses of cholecystokinin-octapeptide, histamine, and acetylcholine. The contractile responses to cholecystokinin-octapeptide and acetylcholine were dependent on the presence of calcium in the bath, with a 40-100% reduction in contraction when buffer with no added calcium was used. In contrast, the contractile response to histamine was unchanged when stimulation was carried out in low calcium buffer. The contractions of the guinea pig gallbladder induced by cholecystokinin octapeptide and acetylcholine, but not histamine, appear to require near physiologic levels of extracellular calcium. PMID- 2920640 TI - Plasma cholecystokinin and gallbladder responses to intraduodenal fat in gallstone patients. AB - Impaired gallbladder emptying is one of the various factors suggested to be involved in the pathogenesis of gallstones. The present study was undertaken to determine whether gallbladder emptying, endogenous cholecystokinin (CCK) secretion, or their interrelation is altered in patients with gallstones. After intraduodenal administration of 60 ml corn oil, plasma CCK concentration was measured by a sensitive and specific radioimmunoassay and gallbladder emptying by cholescintigraphy. Patients with gallstones (N = 20) produced significantly less endogenous CCK (105 +/- 17 pmol/liter 60 min; P less than 0.001) than control subjects (191 +/- 11 pmol/liter 60 min, N = 20); gallbladder emptying in the patients was significantly decreased at 5, 10, 40, 45, and 50 min but the reduction in gallbladder emptying did not reach statistical significance at 60 min (patients 44 +/- 8%, control subjects 60 +/- 4%). In addition, the gallbladder responsiveness to intravenous infusion of the synthetic CCK analog cerulein was investigated. Based on the results of gallbladder emptying in response to endogenous and exogenous CCK, four subgroups of gallstone patients were identified: (1) a group (N = 7) with normal gallbladder sensitivity to CCK, (2) a group (N = 6) with significantly increased gallbladder sensitivity to CCK, (3) a group (N = 6) with impaired gallbladder emptying after corn oil due to a significantly reduced endogenous CCK secretion but with normal gallbladder sensitivity to CCK, and (4) one patient whose gallbladder was unresponsive to CCK and was found to have chronic cholecystitis at surgery. PMID- 2920642 TI - Endoscopic biliary manometry in patients with suspected sphincter of Oddi dysfunction and in patients with cystic dilatation of the bile ducts. AB - We studied the motility of the sphincter of Oddi in 12 patients with suspected sphincter of Oddi dysfunction, in four patients with cystic dilatation of the bile ducts (two Caroli's cases and two fusiform choledochal cyst cases), and in 33 patients with retained common duct stones. In these last 33 patients, the motor activity of the sphincter of Oddi was similar to that recorded in nine control subjects without pancreatic or biliary diseases. In the suspected Oddi dysfunction cases, both the basal sphincteric pressure and the frequency of the phasic contractions were significantly elevated (P less than 0.001). Patients with biliary cystic dilatation showed an increased basal pressure, but the frequency of the contractions was elevated in only those with choledochal cysts and the amplitude in only one of the two patients with Caroli's disease. Motor disorders of the sphincter of Oddi provide a basis for an alternative etiopathogenesis of cystic disease of the biliary system and a possible explanation for pain and dilatation of the bile duct in patients with suspected sphincter of Oddi dysfunction. PMID- 2920643 TI - Physiological gastroesophageal reflux and esophageal motor activity studied with a new system for 24-hour recording and automated analysis. AB - Gastroesophageal reflux and esophageal motility were studied for 24 hr in 32 ambulatory healthy volunteers (20-73 years old), using a newly developed system, consisting of a microprocessor-based data recorder and algorithms for fully automated data analysis. Physiological reflux was more extensive than expected on the basis of widely used normal values. The percentage of time with pH less than 4 and the duration of the reflux episodes increased with age. Of the more than 2000 esophageal contractions occurring per day, peristaltic contractions constituted 50.9 +/- 2.0%. Their amplitude was significantly lower between meals than during meals and during the night. The duration of the peristaltic contractions increased with age. Simultaneous contractions constituted 10.4 +/- 1.2% of the esophageal contractions. Their incidence increased with age. We conclude that continuous ambulatory 24-hr recording with automated analysis of esophageal motility and pH profile is feasible, that the upper limits of normal in ambulatory esophageal pH recording are higher than previously accepted, and that age, meals, and body position must be taken into account in the interpretation of both 24-hr esophageal pH and pressure data. PMID- 2920644 TI - Nonsurgical management of esophageal perforation from pneumatic dilatation in achalasia. AB - Perforation of the esophagus is a well-described complication of pneumatic dilatation in patients with achalasia. Although successful management of these patients without surgical intervention has been reported, little follow-up data exist. We report the successful nonsurgical management of esophageal perforation after pneumatic dilatation in three patients. Manometric and radionuclide esophageal emptying studies in these patients showed satisfactory results after the dilatations despite the occurrence of perforation, and the excellent symptomatic response has been maintained during a follow-up period ranging from one to four years. PMID- 2920645 TI - Proinflammatory effects of local abdominal irradiation on rat gastrointestinal tract. AB - Although the role of inflammatory processes in the genesis of late changes in the gastrointestinal tract following exposure to ionizing irradiation has been extensively studied, few studies have concentrated on the presence of an acute inflammatory response in the period immediately following radiation. We therefore examined, in rats, whether the local application of 10 Gy cobalt-60 irradiation to the abdomen led to changes in the gut within the first 24 hr that were consistent with an acute inflammatory response. In stomach, small intestine, and colon, local irradiation led to a significant increase in the accumulation of plasma within the tissue by 4-8 hr following irradiation. This increase in tissue plasma volume, indicative of an increased microvascular permeability, was then sustained until the end of the 24-hr assessment period in all tissues examined. Concurrent with this was a consistent transient increase in tissue red blood cell volume, suggestive of vasodilation. Of particular note, a significant increase in the number of mucosal neutrophils was also observed between 2 and 12 hr following irradiation. This elevation in mucosal neutrophils was particularly marked in the pericryptal or deep mucosal regions of small intestine and colon and consistently preceded the vasodilation and enhanced permeability. Furthermore these pathophysiological alterations occurred at a time when histological changes in the mucosa consistent with an impaired mucosal microcirculation (ie, edema of the lamina propria and subepithelial bleb formation) were present. These results support the hypothesis that an inflammatory response occurs in the gut during the first 24 hr following abdominal irradiation. Such changes may then further exacerbate the damage initiated by the ionizing radiation. PMID- 2920646 TI - Identification of proline-specific carboxypeptidase localized to brush border membrane of rat small intestine and its possible role in protein digestion. AB - A proline-specific carboxypeptidase (carboxypeptidase P, EC 3.4.12.-) was identified and partially characterized in the brush border membrane fraction of rat intestinal enterocytes and shown to be distinct from pancreatic proteases. The carboxypeptidase activity of isolated brush border membranes, with Z-Gly-Pro Leu as substrate, was 43 nmol/min/mg protein representing a 16-fold purification when compared with mucosal cell homogenates. Activity was maximal in the middle region of the small intestine, and villus cells had twice the activity of crypt cells. Carboxypeptidase activity was maximal at pH 7.0, was stimulated by divalent cations, and was inhibited by metal chelating agents, suggesting that it is a metalloenzyme. The enzyme had the highest activity with synthetic peptides containing proline penultimate to the carboxy terminus. In vivo patterns of hydrolysis and absorption of amino acids from Z-Pro-Trp were examined using an intestinal perfusion technique. These studies indicate that brush border membrane carboxypeptidase may play an important role in the digestion of proline containing peptides and proteins. PMID- 2920647 TI - Effects of gastric fundic stimulation on glucose absorption and water and electrolyte fluxes from rabbit small bowel. AB - A single-pass perfusion model was developed to measure net fluxes of glucose, water, sodium, and potassium across upper jejunal and duodenal mucosa in vivo in the anaesthetised rabbit. Irrigation of the gastric fundic mucosa with Michaelis' buffer (pH 8) reduced jejunal mean glucose absorption by 21.3% (P less than 0.04) and duodenal glucose absorption by 27.2%. Irrigation of gastric fundic mucosa with 0.1 M glycine at pH 2 increased mean jejunal glucose absorption by 25%. Jejunal net secretion of water and sodium were reduced by gastric fundic alkali. Potassium net fluxes in jejunum and duodenum were not significantly affected. These results support the hypothesis that the gastric fundic mucosa is sensitive to chemical stimulation, responding by a humoral mechanism that modified the rate of glucose absorption from the small bowel mucosa. PMID- 2920648 TI - Reduction in index of oxygen saturation at margin of active duodenal ulcers may lead to slow healing. AB - This study tested the hypothesis that reduced perfusion of a duodenal ulcer margin (ie, the mucosa 1-2 mm from the edge of the ulcer base) is associated with slow healing. Reflectance spectrophotometric measurement of indices of mucosal hemoglobin concentration (IHB) and mucosal hemoglobin oxygen saturation (ISO2) were obtained endoscopically in 21 patients at the ulcer margin and the adjacent mucosa (ie, the mucosa 1-2 cm from the edge of the ulcer base). In 17 patients with adequate follow-up, stepwise multilinear regression analysis revealed a significantly negative correlation (r = -0.69, P less than 0.05) between ISO2 at the ulcer margin minus ISO2 at the adjacent mucosa (delta ISO)2 and ulcer healing time. In addition, smoking, being black, and early relapse since the last ulcer attack were found to be associated with increased duration required for healing. The results of this pilot study suggest factors, in addition to smoking, that may have to be considered in future studies concerned with duodenal ulcer healing. PMID- 2920649 TI - Release of protective products, different from prostaglandins, by rat stomachs exposed to mild irritant. AB - The factors responsible for the mediation of mild irritant-induced (adaptive) cytoprotection to the rat stomach are not fully understood. The existence of cytoprotective products that are released by the gastric mucosa in response to its exposure to a mild irritant is assessed in this work. Gastric contents of rats exposed to a mild irritant (0.3 N HCl) or to 0.3 N NaCl (control) were collected, titrated to neutrality, and administered orally to prefasted animals followed by 100% ethanol. Ethanol-induced gross hemorrhagic injury in rats pretreated with the 0.3 N HCl gastric contents were significantly less than in control treated rats (P less than 0.01). Pretreating the donor or recipient rats with indomethacin did not interfere with the generation or protective action of the 0.3 N HCl gastric contents. These findings demonstrate that the exposure of the gastric mucosa to a mild irritant causes the release of protective products, which are different from prostaglandins, into the gastric lumen. PMID- 2920650 TI - Campylobacter pylori in esophagus, antrum, and duodenum. A histological and microbiological study. AB - Two hundred forty-six patients with a wide range of upper gastrointestinal tract disorders were investigated for the presence of Campylobacter pylori infection in esophagus, gastric antrum, and duodenum. C. pylori was identified in 52% of patients in at least one site, and microbiological and histological techniques were used to exclude the presence of the organism. Esophageal infection was not significant and is probably due to reflux. Antral C. pylori was significantly associated with active gastritis and active duodenitis and is possibly pathogenic. PMID- 2920651 TI - Prognosis and prognostic factors in chronic pancreatitis. AB - To evaluate the prognosis and prognostic factors of chronic pancreatitis, 84 patients with alcoholic chronic pancreatitis and 51 with nonalcoholic chronic pancreatitis have been followed for 1-21 years (average of 7.1 years). The follow up period was defined as the period from diagnosis to death in those who died and to the present in those still alive. The following conclusions were obtained. (1) Patients with alcoholic chronic pancreatitis showed a significantly higher mortality rate (26.2%) and cancer death rate (8.3%) than the age- and sex-matched population. In patients with nonalcoholic chronic pancreatitis, however, the difference did not reach the level of statistical significance, although both rates tended to be higher. (2) Patients with alcoholic chronic pancreatitis showed a significantly poorer prognosis than those with nonalcoholic chronic pancreatitis. (3) Frequent causes of death in chronic pancreatitis were cancer (11 cases) and diabetes-associated conditions (renal failure in three cases, intractable pneumonia in one, hypoglycemic shock in two, and myocardial infarction in two). Death directly from pancreatitis was observed in four. (4) Unfavorable prognostic factors in alcoholic chronic pancreatitis included heavy drinking, continuance of drinking after diagnosis, smoking, insulin-dependent diabetes, and an advanced age. In nonalcoholic chronic pancreatitis, however, patients' age was the only significant prognostic factor; smoking did not reach the level of statistical significance, although it tended to lead to a poorer prognosis. PMID- 2920652 TI - Effect of natural peptide YY on pancreatic secretion and cholecystokinin release in conscious dogs. AB - The effects of natural peptide YY on pancreatic secretion under different stimulatory conditions and on fatty acid-induced cholecystokinin release were examined in five conscious dogs with pancreatic and gastric fistulas. Intravenous infusion of natural peptide YY at 1 and 0.2 microgram/kg/hr caused 60 and 40% inhibition of secretin- and cholecystokinin-stimulated secretion, respectively, and 40-50 and 20-40% inhibition of intraduodenal oleate stimulated secretion, respectively. A significant but transient decrease in the plasma cholecystokinin level was observed in response to peptide YY under oleate stimulation. The present study demonstrates that peptide YY has a potent inhibitory effect on both exogenously and endogenously stimulated pancreatic secretion and has a mild suppressive effect on fatty acid-induced cholecystokinin release suggesting that this peptide is an important colonic inhibitor of pancreatic secretion. PMID- 2920654 TI - Use of somatostatin analog in management of carcinoid syndrome. AB - Carcinoid tumors are the most frequent gut neuroendocrine tumors accounting for more than 50% of all tumors of the gastroenteropancreatic (GEP) axis. These tumors appear to derive from a stem cell line capable of differentiating into a variety of malignant cells that secrete many different peptides and amines. The symptoms of carcinoid tumors are often non-specific, vague abdominal pain that may precede the diagnosis by a median of 9 years. Carcinoid syndrome occurs in less than 10% of patients. We evaluated the effects of SMS 201-995 in 14 such patients, 12 with diarrhea, 8 with flushing, 3 with wheezing, one with tricuspid valve incompetence, 6 with facial telangiectasia, 3 with a pellagra type dermatosis and one with myopathy. Diarrhea was abolished or significantly reduced in 83%, flushing in 100%, wheezing in 100%, and myopathy improved in the one patient. Blood serotonin was resistant to change, urine 5HIAA fell in 75%, and most gut neuropeptide hormones apart from somatostatin were suppressed. Tumor growth appeared to be slowed in 2/3 of cases treated for up to 4 years. The analog of somatostatin appears to be a useful addition to the therapeutic armamentarium for carcinoid tumors and the symptom complex. PMID- 2920653 TI - Involvement of pancreatic polypeptide (PP) in luminal feedback regulation in the conscious rat. AB - The possibility of the involvement of pancreatic polypeptide (PP) release in luminal feedback regulation in the conscious rat was examined. Pancreatic secretion in the intestinal phase in the rat is regulated by negative feedback control so that a decrease in luminal protease activities produced by a diversion of bile-pancreatic juice (BPJ) from the intestine stimulates pancreatic secretion. Plasma concentration of rat PP and the effect of exogenous infusion of rat PP on pancreatic secretions during BPJ diversion were determined. Plasma PP concentration significantly increased with BPJ diversion and peaked at 90 min after BPJ diversion began, almost paralleling changes in protein output. Exogenous PP infusion (1, 2 and 10 micrograms/kg/hr) inhibited pancreatic protein and fluid outputs but not the bicarbonate output during BPJ diversion. PP was shown to be physiologically released in the intestinal phase of pancreatic secretion; however, the physiological role of endogenous PP remains unknown. PMID- 2920655 TI - Acute tubular necrosis: preventing complications. AB - Any patient who demonstrates a decrease in urinary output, compromise in hemodynamic parameters, or exposure to nephrotoxic agents will be thoroughly assessed by the critical care nurse for signs or symptoms of acute tubular necrosis (ATN). Prompt recognition of the patient who is at risk, and early nursing interventions, can prevent or improve the course of ATN, the most common form of acute renal failure (ARF). PMID- 2920656 TI - Retention technique #1. Developing managerial warmth. AB - A manager who has interpersonal warmth is not simply gullible or naive, but instead possesses a valuable skill in reaching others. In most manager-employee relationships, some degree of limit-setting and judgment are necessary; however, warmth integrated with limit-setting is more satisfying for both employee and manager. Although warmth as an interpersonal phenomenon is affected by the employee's perception, certain managerial actions can increase the likelihood of being perceived as warm; yet, in spite of careful adherence to the guidelines for communicating warmth, managerial warmth will still be rejected in some situations. As is true of any managerial technique, the effective use of warmth requires an assessment of the employee's personality and the approach most appropriate for the situation at hand. The excellent manager is able to quickly adapt, matching the level of warmth to the situation. See Nurse Manager Retention Factors for viewpoints from nurses themselves. Interpersonal management style is an important retention factor. PMID- 2920657 TI - Building respect: the key to retention. PMID- 2920658 TI - Retention technique #2. Closing critical care beds. AB - The key to nursing retention is to be sensitive to the pressures and demands placed on staff nurses who want to provide and take pride in giving quality patient care. If an institution has many critical care nursing vacancies, it is important to avoid pushing the remaining nurses beyond human limits. It may even be necessary to close beds to keep the remaining nurses, rather than allow the stress of the nursing shortage to cause them to resign too. PMID- 2920659 TI - Retention technique #3. Research: future impact on image and retention. AB - The recruitment, retention, utilization, and image of nursing are critical issues facing nurses today. Critical care nursing research will assist us in dealing with these problems to prepare for a twenty-first century in which nursing is a valued profession. This author takes an optimistic view of the future and explains how she believes nursing research will help solve these recruitment and retention problems. PMID- 2920660 TI - Retention technique #4. Developing retention strategies within your internship program. AB - Internship programs are a well-established method of recruiting and preparing nurses for practice in critical care. This author describes how to incorporate strategies into a program that may enhance the retention of the nurse, following the internship program. PMID- 2920662 TI - Decreased cardiac output: a nursing diagnosis. AB - Controversy exists regarding whether "Decreased Cardiac Output" is really a nursing, or instead, a medical diagnosis. These authors clarify the importance of this diagnosis for nursing care. PMID- 2920661 TI - Retention technique #5. Teaching opportunities: retention of the experienced critical care nurse. AB - Continued career development is an important goal for critical care nurses. Assisting clinical nurses to develop strong teaching skills can promote their career advancement and self-confidence, while increasing retention of these experienced professionals. If you are an experienced nurse interested in developing teaching skills, this article will help you to begin. If you are a manager, educator, or a clinical nurse specialist, the author suggests ideas for helping your expert colleagues develop these abilities. PMID- 2920663 TI - Sex differences in the marital functioning of treated alcoholics. AB - Fifty-five treated alcoholics (31 males and 24 females) were matched with a control group of social drinkers on four dimensions: sex, age, level of education and number of children. Spouses of alcoholic and non-alcoholic respondents were also sampled (total n = 199). Respondents and spouses completed the following questionnaires: The Dyadic Adjustment Scale (DAS), the Areas of Change Questionnaire (AC), and the Marital Status Inventory (MSI). Major results were as follows: (1) Alcoholics reported poorer marital functioning than non-alcoholics. (2) Male alcoholics described less troubled relationships than did female alcoholics. (3) However, spouses of alcoholics described strained marriages in both cases. (4) Alcoholic couples were less congruent than control couples on conscious decisions regarding marital dissolution. (5) Alcoholic wives had taken more steps towards marital dissolution than their husbands had, whereas alcoholic husbands had taken fewer steps than their wives had. It was suggested that male alcoholics externalize their drinking and deny its impact on their marriages, whereas female alcoholics acknowledge their drinking and take the blame for their marital problems. Therapeutic and research implications were discussed. PMID- 2920664 TI - Effects of ethanol on human fractionated response times. AB - The effects of ethanol (EtOH) on response components varying along a central vs. peripheral dimension were studied in five subjects. Reaction times (RTs) were fractionated by electromyographical recordings into premotor (central) and motor (peripheral, contractile) components. Highly practiced subjects performed a simple and discrimination RT task and related movement without significant impairment at the moderate blood ethanol concentration (BEC) (0.10%). At the higher BEC (0.17%), all components involving central processing (response time, RT and premotor time) were impaired in both simple and discrimination RT. More peripheral components (contractile time and movement time) were little affected. Contractile time was slowed slightly but significantly, but only in the combination of EtOH and the discrimination task which suggests that the stimulus discrimination stage of information processing can influence the activation of motor units involved in carrying out the movement. PMID- 2920665 TI - Cognitive functioning of alcoholics and its relationship with prognosis. AB - In a preliminary study a group of 30 alcoholics were subjected to psychological tests to explore the influence of regular alcohol intake on their cognitive functioning and its relationship with prognosis. The functions chosen were, arousal and maintenance of attention, verbal intelligence and performance intelligence. Tests used were the Binet Kamat test of intelligence and Bhatia short scale. Level of education was positively correlated with attention-span and verbal intelligence, but not with performance intelligence. The inter-test discrepancy alone on the performance intelligence test could be assessed for evaluation of cognitive impairment. Poor P.Q. scorers sought medical consultation before their mid thirties and had earlier onset of alcoholism. Elder addicts (above 35 years) showed more abstraction deficiency. The higher the P.Q. the higher was its' positive correlation with adjustment to work, but not to family. PMID- 2920666 TI - High blood lead level in alcoholics: wine vs. beer. AB - One hundred and sixty one alcoholics (121 men and 40 women) were studied during a social rehabilitation program. All had a daily intake of ethanol higher than 1 g/kg/day. The mean lead blood level was 28 micrograms/100 ml and was as high as 72.5 micrograms/100 ml in one subject. Wine drinkers had a higher blood lead level (29.8 micrograms/100 ml) than beer or spirit drinkers (23.8 micrograms/100 ml). A significant correlation was found between the blood lead level and systolic and diastolic arterial blood pressure and this relation was independent of sex, weight or age. We conclude that a high blood lead level can be a risk factor for hypertension in alcoholics. PMID- 2920667 TI - Alcohol and the validation of experimental aggression paradigms: the Taylor reaction time procedure. AB - The aim was to find out whether intoxicated and sober subjects would calibrate a shock scale to the same objective level and whether shocks received would be subjectively experienced in the same way in terms of pain and discomfort. The intention was also to replicate previous studies attributing an aggression enhancing effect to alcohol. The subjective ratings were made within the Taylor reaction time 'aggression machine'. Twenty-four subjects were randomly assigned to either an alcohol or a control group. The former drank 0.8 ml of pure alcohol/kg body wt. Results indicated no differences among groups on a shock setting measure of aggression under unprovoked or provoked conditions and no differences in level of calibration of shocks or in subjective ratings of pain and discomfort. These results were contrary to all predictions and are discussed as indirectly supportive of an hypothesis stating that this version of the 'aggression machine' may not generate a valid measure of aggression when used in alcohol research. PMID- 2920668 TI - Flow cytometric analysis of oxidative product formation in phytohemagglutinin stimulated ethanol-treated immune mononuclear cells. AB - Oxidative products formed by immune mononuclear cells were studied by flow cytometry. JURKAT T cells and peripheral blood mononuclear cells were incubated with 2,7-dichlorofluorescin diacetate. This substance was hydrolysed in the cells, leading to a non-fluorescent product which was oxidized into highly fluorescent 2,7-dichlorofluorescein by oxygen reactive species. These latter products were analysed by flow cytometry in phytohemagglutinin (PHA)-stimulated ethanol (ETH)-treated mononuclear cells. The level of fluorescence intensity (FI) was found higher in stimulated cells than in non-stimulated cells. ETH displayed two different effects on the cells: either a decrease of FI associated with a decrease of the number of fluorescent cells (FC) or an increase in FI. Both effects were dose-dependent. ETH is an effective scavenger of .OH radicals, but it is also oxidized by the microsomal ETH oxidizing system with production of oxygen reactive species, which probably explains the opposite effects of ETH. In the presence of desferal, an iron-chelating agent, and nordihydroguaiaretic acid, an inhibitor of the lipooxygenase pathway, the cells showed a decrease of FI and FC. These results suggest that .OH and other oxygen reactive species are involved in stimulation by PHA of ETH-treated immune mononuclear cells. PMID- 2920669 TI - Effects of dapiprazole, clonidine and yohimbine on the development of dependence and withdrawal behaviour in mice. AB - There is evidence that central noradrenergic hyperactivity is involved in the manifestation of the major signs and symptoms of the opiate withdrawal syndrome. In order to assess whether or not the noradrenergic system is also implicated in the development of opiate dependence, we studied dapiprazole, an alpha-1 selective adrenoceptor antagonist, clonidine and yohimbine using the acute dependence model in mice. When administered just before naloxone, after dependence development, all three drugs reduce abstinence signs. When injected 15 min before morphine to observe the drugs' effects on the development of dependence, dapiprazole depresses all the symptoms registered while clonidine decreases only jumping, but increases paw and head shakes. None of these drugs affects the naloxone precipitated withdrawal syndrome when injected 1 h before morphine. It is suggested that the noradrenergic system is involved in both the manifestation of the withdrawal syndrome and in the development of opiate dependence. Diapiprazole may be a useful tool in patients and in pharmacological studies of dependence and abstinence. PMID- 2920670 TI - Alcoholism--assessment and diagnosis. AB - Ninety-two patients with alcoholism were interviewed on various aspects of alcohol use. Factor analysis of the data revealed five factors: withdrawal symptoms; help seeking behaviour; pathological drinking; legal difficulties; family problems. The analysis suggested the possibility of heterogenity in this clinical sampling with alcoholism. PMID- 2920671 TI - Prospective study of alcoholism treatment in Kuwait: a 5-year follow-up report. AB - The outcome of a 5-year prospective follow-up study of 100 patients treated in the Kuwait Hospital for alcohol-related problems is reported using two parameters computed from weighted follow-up variables, i.e., Offset Score measuring patients' initial follow-up status and Direction of Slope summarizing consequent follow-up scores. Nineteen patients had died representing 14 times the age corrected national rate. Univariate and multivariate analyses of outcome measures against prefollow-up patients' characteristics revealed that variables indicating heavy alcohol use independent of each other predicted negative outcome and mortality. The tendency of the group score distribution towards normalization uninfluenced by treatment is demonstrated. The pertinence of these findings to the medical profession in Kuwait is stressed. PMID- 2920672 TI - Guillain-Barre's syndrome in alcoholics. PMID- 2920673 TI - [Hereditary dysprothrombinemia with a mild bleeding tendency (prothrombin Magdeburg)]. AB - Seven members of one family over three generations were found to have a characteristic reduction to about 0.5 of the ratio between factor II clotting activity and factor II concentration, which was not seen when measuring prothrombin after activation with staphylocoagulase. In addition to the "normal" prothrombin, two abnormal prothrombins, with higher molecular weights and lower isoelectric points, were found by SDS-polyacrylamide gel electrophoresis. This is an autosomal hereditary dysprothrombinemia, the affected persons being heterozygotes. Five of the seven persons had a slightly increased bleeding tendency which manifested itself especially in more marked or prolonged posttraumatic and postoperative bleedings. PMID- 2920674 TI - [Neutropenic enterocolitis]. AB - In three patients with neutropenia who had died after a short period from their basic disease (myelodysplasia, medullary carcinoma, acute myeloic leukaemia), autopsy revealed segmental necrotising enterocolitis in the caecal region (neutropenic enterocolitis). Morphologically the enterocolitis was characterised by necrotized mucosa, marked oedema of the intestinal wall, intramural gas, the absence of pseudomembranes and a nearly complete absence of inflammatory cell infiltrates. In one case a palpable abdominal tumour had been produced by pseudotumorous thickening of the intestinal wall. The pathogenesis in these three cases might be a neutropenia-associated disturbance of the intestinal flora with selective proliferation of toxin-producing clostridia. PMID- 2920675 TI - [Endocardial dual-chamber stimulation in an anomalous persistent left superior vena cava]. AB - A persistent left superior vena cava was noted in a 63-year-old woman during pacemaker implantation because of sinus bradycardia and AV dissociation. During atrial test stimulation a 2 degree AV block occurred at a rate of only 110/min and dual-chamber provision was thus necessary. Both catheters were introduced into the right heart via the coronary sinus, but placement of the right ventricular lead was made more difficult than usual because of looping. One year later pacemaker function (DDI mode) was unchanged and the patient symptom-free. PMID- 2920676 TI - [Long-term storage of autologous blood in case of vital need]. PMID- 2920677 TI - [Side effects of a cartilage extract]. PMID- 2920678 TI - [Tumor patients and alternative medicine. Attempt at characterizing users of alternative treatment methods in oncology]. AB - 161 oncological outpatients at Basel University hospital were anonymously questioned as to their motives for undergoing treatment methods which had not been proven efficacious. 71 patients stated that they were using unconventional remedies, principally diet and anthroposophical treatment. "Building up resistance" (87%) and "supplementary treatment" (69%) were the main reasons given. A lack of confidence in conventional medicine (6%) or failure of previous therapy (4%) was less important. In attempting to characterize users and non users of unorthodox medical treatments in this group of patients significant differences were revealed in the patients' political and religious convictions, as well as their health consciousness. Users more often described themselves as "left-wing" or "ecologically-orientated", and more frequently experienced a strengthening of their religious faith through their illness. No differences could be determined as to age, sex, family status or attitude toward disease. PMID- 2920679 TI - [Pharmacokinetics of cisplatin in long-term hemodialysis treatment]. AB - A 66-year-old woman with ovarian cancer which had metastasized was receiving chemotherapy with cisplatin and cyclophosphamide while undergoing haemodialysis for chronic renal failure. Cisplatin concentration in plasma was measured by flameless atomic absorption spectroscopy. After infusion of 40 mg cisplatin/m2 body-surface peak levels of 2.06 micrograms/ml and 2.29 micrograms/ml were obtained after the second and third treatment cycles, respectively. Terminal half life was 14 days. Clearance value during haemodialysis was 470 ml/min. Seven treatment cycles were administered, up to doses of 60 mg/m2 cisplatin and 600 mg/m2 cyclophosphamide. Complete remission occurred after five treatment cycles. But the patient died 22 months after onset of treatment from an acute non-A, non B hepatitis. PMID- 2920680 TI - [Magnetic resonance and computed tomography in brain evaluation]. PMID- 2920681 TI - [Ciprofloxacin management of pelvic inflammation caused by Salmonella panama]. PMID- 2920682 TI - [Psychophysiologic loads amplify clinical stress tests]. PMID- 2920683 TI - [Midazolam causing respiratory arrest and hypotension]. PMID- 2920685 TI - [Is biochemical screening for alcohol abuse ethical?]. PMID- 2920684 TI - [A case of polyradiculitis with EKG deviations and weakened heart sounds]. PMID- 2920686 TI - [Diagnosis and treatment by orthopedic manipulation]. PMID- 2920687 TI - [Rehabilitation of limb amputees]. PMID- 2920688 TI - [Physiatric health promotion]. PMID- 2920689 TI - [Physiatrics of the elderly as a special group]. PMID- 2920690 TI - [Physiotherapy is a humane interaction]. PMID- 2920691 TI - [The physiatric contribution to physical fitness]. PMID- 2920692 TI - [The physiatric management of orthopedic patients]. PMID- 2920693 TI - [The physiatric management of potential axial and locomotor diseases]. PMID- 2920694 TI - The relationship of frog pressure to heel expansion. AB - A study was carried out on five horses and four ponies to assess the effect of altering frog pressure on hoof expansion. Measurements of hoof expansion were made using strain gauges. It was concluded that whereas frog pressure affects hoof expansion, it is only one of several factors. Increasing frog pressure may result in increased expansion, or contraction, or may have virtually no affect. The variable results of changing frog pressure should be taken into account when considering therapeutic shoeing. PMID- 2920695 TI - A technique for assessing hoof function in the horse. AB - This paper describes the application of foil strain gauges to the hoof wall, and the use of measuring equipment to monitor weightbearing and changes in hoof shape in shod and unshod horses. It concludes that the systems can detect hoof movement and that results are reproducible. It is also concluded that the use of a conventional nailed on iron shoe restricts flexion and spreading of the hoof wall at the ground surface, but has little effect on the degree of expansion of the heels of the foot. PMID- 2920696 TI - Comparison of transtracheal aspirate and bronchoalveolar lavage cytology in 50 horses with chronic lung disease. AB - Comparisons were made between transtracheal aspirate (TTA) and bronchoalveolar lavage (BAL) cytology obtained from 50 horses with chronic lung disease and from 10 control horses. There was no significant correlation between the TTA cytology and the BAL cytology, suggesting that the cell population in the trachea is not representative of the cell population in the lower airways. In control horses the range of differential cell counts obtained from TTA fluid was remarkably large, whereas the variability in cell populations observed in BAL fluid was smaller. In the principal horses the total and differential cell counts of the TTA and BAL fluids were within the 95 per cent confidence interval in 38 and 24 per cent of cases, respectively; and an increase in percentage neutrophils was most common. It was concluded that BAL may be a useful diagnostic aid when evaluating horses with chronic lung disease, but that the clinical usefulness of cytological evaluations of TTA fluid may be limited in these cases. PMID- 2920697 TI - Muscular adaptation of horses during intensive training and detraining. AB - Five horses were studied during a five-week regime of controlled intensive daily training on a high-speed treadmill followed by five weeks of detraining. Muscle biopsies were taken weekly from both the right and left gluteus muscle and from the sternocephalicus muscle before, and at the end of, the training and detraining periods. Histochemical and biochemical analyses of the sternocephalicus muscle showed no metabolic adaptation with either training or detraining. No significant differences were observed in any of the analysed parameters in the gluteus muscle between contralateral sites. Glycogen levels decreased by 10 to 15 per cent after one to two weeks of training, remained low during the training period and increased to pretraining levels after one week's cessation of training. Citrate synthase activity increased rapidly and was 27 per cent higher after one week and 42 per cent higher after five weeks of training. Lactate dehydrogenase activity decreased by 15 per cent during this period. The changes seen in these enzyme levels persisted during the detraining period. No alterations were seen in fibre type composition but type IIA fibre areas decreased by 19 per cent after five weeks training and capillary density increased by 17 per cent. It is concluded that a period of intensive training will rapidly increase the oxidative capacity and the capillary density in an actively working muscle, and that these metabolic adaptations are well maintained during a subsequent period of detraining. PMID- 2920698 TI - Interactions between chloramphenicol, acepromazine, phenylbutazone, rifampin and thiamylal in the horse. AB - The potential for interactions between chloramphenicol, phenylbutazone, acepromazine and thiamylal and chloramphenicol, rifampin, and phenylbutazone were evaluated in two groups of experiments. In the first, five horses were given thiamylal intravenously (iv) (6.6 mg/kg) after pretreatment with acepromazine, and the time of recumbency was determined. Administration of chloramphenicol iv (25 mg/kg) 1 h prior to anaesthesia significantly lengthened the recumbency time from 21.8 +/- 4.8 mins to 36.0 +/- 8.3 mins. There was an apparent but not statistically significant decrease in recumbency time when phenylbutazone (4.4 mg/kg) was administered iv daily for 4 days prior to anaesthesia. In the second series of experiments, phenylbutazone (4.4 mg/kg), chloramphenicol (25 mg/kg) and rifampin (10 mg/kg) were administered in various sequences to five different horses. Chloramphenicol pretreatment produced a significant decrease in the elimination rate and rifampin a significant increase in the elimination rate of phenylbutazone. The half-life of elimination of phenylbutazone alone was about 4 h. Following four days pretreatment with rifampin it was approximately 2.7 h, it was approximately 5.6 h and 9.5 h, respectively, when chloramphenicol was administered in one dose 1 h before or two doses 12 h and 1 h before phenylbutazone. PMID- 2920699 TI - Left ventricular function and haemodynamics in ponies during exercise and recovery. AB - Myocardial and haemodynamic responses to strenuous treadmill exercise were monitored with chronically implanted instrumentation in seven physically untrained ponies. In two other ponies, haemodynamics were monitored using a conventional catheter technique. During exercise (mean +/- sem heart rate = 203 +/- 3 beats/min), left ventricular peak systolic ahd end-diastolic blood pressure significantly increased from 125 +/- 2 to 208 +/- 6 mmHg and from 29 +/- 1 to 58 +/- 3 mmHg, respectively (P less than 0.05). Peak positive first derivative of left ventricular pressure (dP/dt) was also increased significantly, (1397 +/- 144 to 6016 +/- 325 mmHg/sec), as were myocardial segment velocity of shortening during systole (dL/dtsys) and stroke work (193 and 109 per cent, respectively). Paradoxically, segment systolic shortening was reduced significantly (P less than 0.05) with respect to resting control values for 10 mins after cessation of exercise, with the maximal reduction of 22 per cent occurring at 2 mins post exercise. In addition, left ventricular segment stroke work decreased significantly to 67 per cent of resting control value at 2 mins post exercise. This study demonstrates that analysis of regional myocardial performance in conjunction with haemodynamic data permits a detailed description of cardiac events during and immediately following exercise, facilitating definition of changes which are not readily reflected by haemodynamics. Based on these findings, the authors conclude that untrained ponies may readily complete short bouts of near-maximal exercise, yet experience significantly diminished left ventricular function in the immediate post exercise period. PMID- 2920700 TI - Effect of freeze-drying on measurements of pH in biopsy samples of the middle gluteal muscle of the horse: comparison of muscle pH to the pyruvate and lactate content. AB - Muscle biopsies taken after exercise, in comparison to those at rest, contain increased amounts of blood and this is a particular problem in studies of the horse. The inclusion of blood in muscle will introduce an upward bias in values of pH measured in muscle homogenates. In an attempt to control this, muscle biopsy samples of the middle gluteal from Thoroughbred horses were freeze-dried and dissected free of blood before determination of pH. Following exercise, muscle pH measured after freeze-drying was similar to that measured in homogenates prepared from frozen samples. In contrast, freeze-drying appeared to increase muscle pH in samples taken at rest. This was probably the result of loss of CO2 during freeze-drying. Muscle pH determined in freeze-dried samples taken at rest and after exercise was linearly related to pyruvate and lactate content (P less than 0.001). It is concluded that muscle samples taken after exercise can be freeze-dried and dissected free from blood before determination of pH, whereas this procedure will cause an alkaline shift in samples taken at rest. PMID- 2920701 TI - Use of high-speed cinematography and computer generated gait diagrams for the study of equine hindlimb kinematics. AB - High-speed cinematography with computer aided analysis was used to study equine hindlimb kinematics. Eight horses were filmed at the trot or the pace. Filming was done from the side (lateral) and the back (caudal). Parameters measured from the lateral filming included the heights of the tuber coxae and tailhead, protraction and retraction of the hoof and angular changes of the tarsus and stifle. Abduction and adduction of the limb and tarsal height changes were measured from the caudal filming. The maximum and minimum values plus the standard deviations and coefficients of variations are presented in tabular form. Three gait diagrams were constructed to represent stifle angle versus tarsal angle, metatarsophalangeal height versus protraction-retraction (fetlock height diagram) and tuber coxae and tailhead height versus stride (pelvic height diagram). Application of the technique to the group of horses revealed good repeatability of the gait diagrams within a limb and the diagrams appeared to be sensitive indicators of left/right asymmetries. PMID- 2920702 TI - Effects of season and lower ambient temperature on the structure of the sweat glands in anhidrotic horses. AB - Histological studies of the sweat glands of anhidrotic horses in the Hong Kong summer and under conditions of reduced thermal stress, both natural and controlled, were undertaken to determine if glandular regeneration occurs. Clinical data were collected for comparison with the histological results in each instance. Horses were assigned to one of three categories on the basis of the resulting change in the number of thin glandular profiles in a cooler environment. Group 1, which was classed as normal, had a low initial value, which was maintained. Group 2, typical of mild and moderately affected animals, had a high initial value, which fell markedly after as little as six weeks in the cool environment. Animals in Group 3, classed as severely affected, had a high initial value which remained high even after prolonged exposure to the cool environment. Light microscopical examination of the sweat glands in the heat, and after six weeks in a cool environment, provided a means of predicting the degree of anhidrotic severity and the potential for recovery in a cool climate. This was superior to clinical observation, although a diagnostic test based on glandular function is still required. PMID- 2920703 TI - Three cases of paroxysmal atrial fibrillation in the Thoroughbred newborn foal. PMID- 2920704 TI - Autosomal trisomy in a Standardbred colt. PMID- 2920705 TI - Uterus bicollis in a Clydesdale mare. PMID- 2920706 TI - Subchondral osseous cyst formation after an intra-articular fracture in a filly. PMID- 2920707 TI - Light and electron microscopic changes in sural nerves in Ethiopian diabetics. AB - The light and electron microscopic morphological changes in sural nerve biopsies from 32 Ethiopian diabetics and 4 malnourished non-diabetic subjects were studied in order to determine the role of malnutrition in the development of diabetic neuropathy. The most prominent finding in diabetics with clinical neuropathy was reduction in the density of myelinated axons of all diameters especially the large ones. Affected nerves showed abundant intraneural collagen, and evidence of nerve regeneration in some cases. Demyelination, though present, was less marked. Changes in the vasa nervorum were seen in only one case. The morphological changes correlated with the duration and severity of the diabetes and with nerve conduction velocity. No changes were seen in malnourished non-diabetics and diabetics without clinical neuropathy, thus suggesting that malnutrition by itself does not contribute significantly to the development of diabetic neuropathy. Axonal degeneration appears to be the predominant feature in diabetic neuropathy. PMID- 2920708 TI - The frequency of multiple births in Gondar Hospital northwestern Ethiopia. AB - The frequency of multiple births was analysed using data on 12287 deliveries conducted at the Gondar College of Medical Sciences Teaching Hospital in Northwestern Ethiopia, between 1977 and 1985. There were a total of 183 multiple births giving a frequency of 14.9 per thousand deliveries. The prevalence rates of twins and triplets were 14.4 and 0.49 per thousand deliveries respectively. Increasing rates of twinning by maternal age and parity were observed, the peak prevalence was seen after the sixth parity and in mothers 40-44 years old. Using Weinberg's differential method, the monozygous and dizygous twinning rates per thousand deliveries were 4.8 and 11.7 respectively. The latter rate tended to increase with both parity and maternal age. The findings of this study suggest a lower frequency of multiple births than in previous reports from Ethiopia and other African countries and hence are not characteristic of the continent. The rates found occupy an intermediate position between those for Caucasians and Africans. Multicentre data should, therefore, be analysed to confirm the findings of this and other reports concerning multiple births in Ethiopia. PMID- 2920709 TI - Sensitivity patterns of bacteria isolated from patients at Sidamo Regional Hospital. AB - This study from the Sidamo Regional Hospital presents the prevailing sensitivity to common antimicrobials among 337 bacterial isolates from abscesses, infected wounds, urine or gonorrhoeal infections. As expected, Staphylococcus aureus Escherichia cloi, Proteus supp and Streptococcus pyogenes were most frequently grown from abscesses and infected wounds, whereas E. coli, Proteus spp, Klebsiella spp, and coagulase negative staphylococci dominated in urinary tract infections. Very high rates of reduced sensitivity, including multiresistance to commonly used antibiotics, were detected. Of 54 isolates of Niesseria gonorrhoeae 84% were resistant to penicillin-G by disc diffusion method. Beta lactamase production was detected in 4 of 6 isolates tested. PMID- 2920710 TI - Histopathological features of liver disease in hospitalized Ethiopian patients. AB - A retrospective analysis of 860 liver biopsy specimens processed by the Department of Pathology of Addis Ababa University was made to determine the frequencies of the various histopathological lesions seen among Ethiopians admitted with liver disease. One hundred fifty six (18.1%) of the specimens were inadequate for precise pathological diagnosis. Liver cirrhosis accounted for 25.4% (179) and primary hepatocellular carcinoma for 19.2% (135) of all diagnoses. Porphyria cutanea tarda was diagnosed in 12.4% (87) of the biopsy specimens. Hepatitis, metastases to the liver, and hepatic granulomata were present in 8.8% (62), 4.5% (32) and 2.8% (20) of the specimens respectively. In countries like Ethiopia where autopsies and diagnostic facilities are limited, and liver diseases prevalent, percutaneous needle biopsy is a useful procedure to define the histopathology of different types of liver disease. PMID- 2920711 TI - The effect of high altitude on saliva aldosterone and glucocorticoid concentrations. AB - Saliva was collected from six healthy young men at hourly intervals at sea level and after 1-2, 8-9 and 15-16 days at 4450 m on Mount Kenya for measurement of aldosterone (SA) and glucocorticoid (SGC, cortisol + cortisone) concentrations. Blood samples were collected simultaneously with some of the saliva samples and analysis of these showed that plasma and saliva concentrations of aldosterone and glucocorticoids were highly correlated (r = 0.91 and 0.75 respectively; p less than 0.01 for both hormones). Mean SA for the group was reduced to approximately 50% of the sea-level value (p less than 0.05) by the time the first saliva samples were collected at altitude, and remained at this depressed level throughout the 2-week period on Mount Kenya, although there was considerable inter-subject variation. SGC concentration also tended to be lower on Mount Kenya than at sea level. Though SA was lower throughout the day at altitude compared to sea level, the principal difference in the temporal pattern of SA was the reduction or complete absence of the marked rise in SA that normally occurs in the first few hours after rising. SA and SGC responses to exercise, which consisted of stepping on and off and 0.4-m high stool 60 times/min for 25 min, were assessed at sea level and after various periods at 4450 m.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2920712 TI - Predictors of sweat loss in man during prolonged exercise. AB - Nineteen healthy male subjects, differing in training status and Vo2max (52 +/- 1 ml.min-1.kg-1, mean +/- SEM; 43-64 ml.min-1.kg-1, range), exercised for 1 h at an absolute workload of 192 +/- 8 W (140-265 W); this was equivalent to 70 +/- 1% Vo2max (66-74%). Each exercise test was performed on an electrically braked cycle ergometer at a constant ambient temperature (22.5 +/- 0.0 degrees C) and relative humidity (85 +/- 0%). Nude body weight was recorded prior to and after each exercise test. Absolute sweat loss (body weight loss corrected for respiratory weight loss) during each test was 910 +/- 82 g (426-1665 g); this was equivalent to 1.3 +/- 0.1% (0.7-2.2%) of pre-exercise body weight (relative sweat loss). Weighted mean skin temperature and rectal temperature increased after 5 min of exercise from 30.5 +/- 0.3 degrees C and 37.2 +/- 0.1 degrees C respectively to 32.5 +/- 0.2 degrees C and 38.8 +/- 0.1 degrees C respectively, recorded immediately prior to the end of exercise. Bivariate linear regression and Pearson's correlation demonstrated absolute sweat loss was related to Vo2max (r = 0.72, p less than 0.001), absolute exercise workload (r = 0.66, p less than 0.01), body surface area (r = 0.62, p less than 0.01), weight (r = 0.60, p less than 0.01) and height (r = 0.53, p less than 0.05). Relative sweat loss was related to VO2max (r = 0.77, P less than 0.001) and absolute exercise workload (R = 0.59, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2920713 TI - Flexibility of the shoulder joint measured as range of abduction in a large representative sample of men and women over 65 years of age. AB - In a representative survey of 1000 elderly men and women aged over 65 years living in their own homes, assessments have been made of flexibility measured as range of shoulder abduction in addition to health status, psychological well being and reported customary activity. The results for shoulder abduction were approximately normally distributed and the mean values (+/- 1 standard deviation) were as follows: - in men aged 65-74 years, 129 (+/- 14) degrees and aged over 74 years, 121 (+/- 19) degrees; in women aged 65-74 years, 124 (+/- 19) degrees and aged over 74 years, 114 (+/- 22) degrees. These mean values are about 30 degrees less than those accepted for younger subjects. Nearly half the distribution falls below the accepted threshold level of 120 degrees for adequate function. There were significant effects of sex and age (P less than 0.001); women had poorer flexibility and the reduction with age amounted to 10 degrees per decade. Multiple regression analysis showed that the effect of age was accounted for in part by health, strength and customary use. The effects of use were most marked in those with some disability. This suggests that maintained or increased use could offset some of the age-related loss of the range of shoulder movement. PMID- 2920714 TI - The fatigability of two agonistic muscles in human isometric voluntary submaximal contraction: an EMG study. I. Assessment of muscular fatigue by means of surface EMG. AB - During an external isometric constant torque (25% of the maximal voluntary contraction) maintained until the maximal endurance time (limit time), we analysed and compared the changes in electromyographic (EMG) activity illustrating muscular fatigue simultaneously with mechanical activity (the tangential acceleration theta") related to physiological tremor. The EMG activities recorded were of two agonistic flexors, the biceps brachii (BB) and the brachioradialis (BR) muscles and one of the main extensors, the triceps brachii (TB). The integrated EMG increase and the mean power frequency (MPF) of the power spectrum density function (PSDF) decrease were larger for BR than for BB activity. These two findings suggested a greater BR fatigability. However, it is shown that differences between BB and BR MPF changes could be related to differences in the PSDF upper frequency limit of the two muscles and also to the relative magnitude of their tremor component. PMID- 2920715 TI - The fatigability of two agonistic muscles in human isometric voluntary submaximal contraction: an EMG study. II. Motor unit firing rate and recruitment. AB - The recruitment and firing rate of biceps brachii (BB) and brachioradialis (BR) motor units (MUs) were studied in the course of fatiguing isometric contractions at 20%-30% of maximal voluntary contraction (MVC). MU recruitment generally occurred throughout the maintained contraction and was similar for BB and BR muscles. Newly recruited MUs started to discharge in the form of bursts, the duration of which increased until a continuous rhythmical firing was achieved. Within each burst, the first interval between two consecutive discharges was usually the shortest. MU threshold was lowered just after the limit time of the maintained contraction. The MU's firing rate either increased or remained stable as a function of the elapsed time. It is concluded that (1) in fatiguing isometric contractions at 20%-30% MVC contractile failure is mainly compensated for by MU recruitment and a lowered MU threshold and (2) differences between in surface changes in the electromyogram of BB and BR muscles cannot easily be explained by related differences in MU firing rate and recruitment. PMID- 2920716 TI - Comparison between a 30-s all-out test and a time-work test on a cycle ergometer. AB - The relationship between the amount of work (Wlim) performed at the end of constant-power exhausting exercise and exhaustion time (tlim) has been studied for supramaximal exercise [105%, 120%, 135% and 150% of the individual maximal aerobic power, (MAP)] performed on a Monark cycle ergometer in nine men. The Wlim -tlim relationship was described by a linear relationship (Wlim = a + b . tlim). Intercept a was roughly equivalent to the work produced during a 1-min exercise performed at MAP. Slope b was equal to 79% of MAP. Intercept a has been correlated with the total amount of work (AW) performed during a 30-s all-out test supposed to assess anaerobic capacity. Intercept a was significantly (p less than 0.05) correlated with AW. The anaerobic capacity was not depleted at the end of the all-out test, as the mechanical power at the 30th s of this test was approximately equal to twice MAP. However, AW was significantly higher than intercept a. It was likely that the value of intercept a was an underestimation of the maximal anaerobic capacity because of the inertia of the aerobic metabolism. Indeed, an exponential model of the Wlim--tlim relationship, which takes the interia of the aerobic metabolism into account, shows that a linear approximation of the Wlim--tlim relationship yields a systematic underestimation of the anaerobic capacity. Consequently, intercept a of the Wlim--tlim relationship is not a more accurate estimation of the anaerobic capacity than the AW performed during a 30-s all-out test.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2920717 TI - Plantarflexor muscle function in young and elderly women. AB - Contractile properties of the ankle plantarflexor muscles were compared between groups of young (means = 26 y) and elderly (means = 82 y) women. The H-reflex muscle contraction in the elderly group was characterized by a significant slowing of torque generation, as compared to the young women (means for average rate of torque development were young = 0.16 Nm ms-1 +/- 0.02 (SE), elderly = 0.09 Nm ms-1 +/- 0.02, P less than 0.05). However, the proportion of the total motor unit pool activated by the reflex was similar for the young and elderly groups at 63% and 70%, respectively. Maximal voluntary isometric torques were significantly lower (71%) in the elderly (young means = 135.3 Nm +/- 9.3, elderly means = 39.2 Nm +/- 2.9, P less than 0.01). These results are consistent with, and extend, previous reports showing decreased strength and speed of contraction in elderly muscle. Given that the average body weight was similar for the young and elderly groups, it was concluded that the aged plantarflexor muscles exhibited considerable impairment in ability to generate stabilizing torques about the ankle joint. PMID- 2920718 TI - Comparison of twitch potentiation in the gastrocnemius of young and elderly men. AB - The capacity for twitch potentiation in the gastrocnemius muscle was determined following maximal voluntary contractions (MVC) in 11 elderly (means +/- SD; 66.9 +/- 5.3 years) and 12 young (25.7 +/- 3.8 years) men. Potentiation was observed by applying selective stimulation to the muscle belly, 2 s after a 5 s MVC. With this procedure, both groups showed significant (P less than 0.05) increases in twitch tension in the gastrocnemius (ratios of potentiated twitch to baseline were means = 1.68 +/- 0.40 for young vs means = 1.40 +/- 0.20 for the elderly, P less than 0.001). Time to peak tension of the twitch decreased from means = 101.5 +/- 17.9 ms to means = 88.0 +/- 15.8 ms in the young men following potentiation; the respective values for the older men were 136.7 +/- 17.9 ms and 133.1 +/- 28.6 ms. These changes resulted in a greater rate of tension development in the potentiated state. The elderly gastrocnemius thus showed qualitatively similar changes in the isometric twitch following potentiation, but reduced and prolonged responses in comparison to young adults. Slowed muscle contraction and reduced capacity for potentiation may be physiological correlates of the reported morphological changes in aged skeletal muscle. PMID- 2920719 TI - Influence of cold exposure on blood lactate response during incremental exercise. AB - This study examined the effect of acute exposure of the whole body to cold on blood lactate response during incremental exercise. Eight subjects were tested with a cycle ergometer in a climatic chamber, room temperature being controlled either at 24 degrees C (MT) or at -2 degrees C (CT). The protocol consisted of a step increment in exercise intensity of 30 W every 2 min until exhaustion. Oxygen consumption (VO2) was measured at rest and during the last minute of each exercise intensity. Blood samples were collected at rest and at exhaustion for estimations of plasma norepinephrine (NE), epinephrine (E), free fatty acid (FFA) and glucose concentrations, during the last 15 s of each exercise step and also during the 1st, 4th, 7th, and the 10th min following exercise for the determination of blood lactate (LA) concentration. The VO2 was higher during CT than during MT at rest and during nearly every exercise intensity. At CT, lactate anaerobic threshold (LAT), determined from a marked increase of LA above resting level, increased significantly by 49% expressed as absolute VO2, and 27% expressed as exercise intensity as compared with MT. The LA tended to be higher for light exercise intensities and lower for heavy exercise intensities during CT than during MT. The E and NE concentrations increased during exercise, regardless of ambient temperature. Furthermore, at rest and at exhaustion E concentrations did not differ between both conditions, while NE concentrations were greater during CT than during MT. Moreover, an increase off FFA was found only during CT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2920720 TI - Effects of pre-motion electromyographic silent period on dynamic force exertion during a rapid ballistic movement in man. AB - The effects of pre-motion silent period (PSP) on dynamic force exertion were studied in ten healthy subjects performing ballistic elbow extensions. The experiments were designed to evaluate the significance of mean differences between the averaged dynamic force curves of two groups: PSP-presence groups and PSP-absence groups. The presence of PSP was judged quantitatively and automatically by means of a newly developed method using statistical analysis. The results indicated that there were two effects of PSP on dynamic force exertion: one was a reducing effect, observed prior to the movement; the other was a reinforcing effect, observed in the first part of the ballistic movement. The duration of the reinforcement was significantly correlated with the duration of the reducing effect of PSP. The findings suggested that the reinforcement of dynamic force may be produced by the pre-stretch of agonistic muscles caused by prior force reduction due to PSP occurrence. The fact that PSP plays an important role in dynamic force exertion suggests that PSP may be incorporated in the central motor control system designed to interrupt the background activity, to stretch the agonist and to reinforce the dynamic force. PMID- 2920721 TI - Gastric emptying during exercise: effects of heat stress and hypohydration. AB - To determine the effects of acute heat stress, heat acclimation and hypohydration on the gastric emptying rate of water (W) during treadmill exercise, ten physically fit men ingested 400 ml of W before each of three 15 min bouts of exercise (treadmill, approximately 50% VO2max) on five separate occasions. Stomach contents were aspirated after each exercise bout. Before heat acclimation (ACC), experiments were performed in a neutral (18 degrees C), hot (49 degrees C) and warm (35 degrees C) environment. Subjects were euhydrated for all experiments before ACC. After ACC, the subjects completed two more experiments in the warm (35 degrees C) environment; one while euhydrated and a final one while hypohydrated (-5% of body weight). The volume of ingested water emptied into the intestines at the completion of each exercise bout was inversely correlated (P less than 0.01) with the rectal temperature (r = -0.76). The following new observations were made: 1) exercise in a hot (49 degrees C) environment impairs gastric emptying rate as compared with a neutral (18 degrees C) environment, 2) exercise in a warm (35 degrees C) environment does not significantly reduce gastric emptying before or after heat acclimation, but 3) exercise in a warm environment (35 degrees C) when hypohydrated reduces gastric emptying rate and stomach secretions. Reductions in gastric emptying appear to be related to the severity of the thermal strain induced by an exercise/heat stress. PMID- 2920722 TI - Gastric emptying during walking and running: effects of varied exercise intensity. AB - Gastric emptying is increased during running (50%-70% maximal aerobic uptake, VO2max) as compared to rest. Whether this increase varies as a function of mode (i.e. walking vs running) and intensity of treadmill exercise is unknown. To examine the gastric emptying characteristics of water during treadmill exercise performed over a wide range of intensities relative to resting conditions, 10 men ingested 400 ml of water prior to each of six 15 min exercise bouts or 15 min of seated rest. Three bouts of walking exercise (1.57 m.s-1) were performed at increasing grades eliciting approximately 28%, 41% or 56% of VO2max. On a separate day, three bouts of running (2.68 ms-1) exercise were performed at grades eliciting approximately 57%, 65% or 75% of VO2max. Gastric emptying was increased during treadmill exercise at all intensities excluding 75% VO2max as compared to rest. Gastric emptying was similar for all intensities during walking and at 57% and 65% VO2max during running. However, running at 74% VO2max decreased the volume of original drink emptied as compared to all lower exercise intensities. Stomach secretions were markedly less during running as compared to walking and rest. These data demonstrate that gastric emptying is similarly increased during both moderate intensity (approximately 28%-65% VO2max) walking or running exercise as compared to resting conditions. However, gastric emptying decreases during high intensity exercise. Increases in gastric emptying during moderate intensity treadmill exercise may be related to increases in intragastric pressure brought about by contractile activity of the abdominal muscles. PMID- 2920723 TI - Effects of estrus cycle on thermoregulatory responses during exercise in rats. AB - In female rats, rectal temperature (Tre), tail vasomotor response, oxygen uptake (VO2), and carbon dioxide production (VCO2) were measured in proestrus and estrus stages during treadmill running at two different speeds at an ambient temperature (Ta) of 24 degrees C. Experiments were performed at 2.00-6.00 a.m., when the difference in Tre was greatest between the two stages; Tre at rest in the estrus stage was 0.54 degrees C higher than in the proestrus stage. In a mild warm environment, threshold Tre for a rise in tail skin temperature (Ttail) was also higher in the estrus stage than in the proestrus stage. In contrast, no difference was seen in the threshold Tre and steady state Tre at the end of exercise between proestrus and estrus stages. These values were higher at the higher work intensity. VO2 was also similar between the two stages, except in the second 5 min after the beginning of exercise, when VO2 was greater and Tre rose more steeply in the proestrus stage. These data indicate that deep body temperature during exercise is regulated at a certain level depending on the work intensity and is not influenced by the estrus cycle. PMID- 2920724 TI - Enzyme nomenclature. Recommendations 1984. Supplement 2: corrections and additions. PMID- 2920725 TI - Characterization of a 48-kDa nucleic-acid-binding fragment of nucleolin. AB - Nucleolin (C23 or 100 kDa) is an abundant single-stranded-nucleic-acid-binding nucleolar protein proposed to be involved in the early stages of ribosome assembly. A stable 48-kDa fragment of the protein was produced either by proteolytic activity present in nucleolar extracts or by added trypsin. The hydrodynamic and DNA-binding properties of the 48-kDa fragment were compared with the parent molecule. Protein sequencing indicated that the fragment begins at residue 282; amino acid composition of the fragment including 10-12 methylated arginine residues suggested that the fragment contains the entire COOH-terminal two-thirds of the protein. The 48-kDa fragment was more globular than nucleolin, as indicated by a lower frictional coefficient (1.3 vs. 2.0 for nucleolin) and a similar sedimentation coefficient (4.1-4.3S) in spite of the reduction in molecular mass. Although the 48-kDa fragment retained single-stranded-DNA-binding activity, the binding capacity and the ability to reassociate DNA were about fivefold and sixfold lower, respectively, than nucleolin. Similarly, tenfold higher concentrations of the 48-kDa fragment were required to form nucleoprotein aggregates. These results suggest that nucleolin contains a globular COOH terminal domain for nucleic-acid binding and a NH2-terminal region which is involved in protein-protein interactions and modulating nucleic-acid-binding activity. PMID- 2920726 TI - Comparative characterization of membrane-associated and cytosolic Tyr-protein kinases in human erythrocytes. AB - In recent years, two protein-tyrosine kinase activities, phosphorylating tyrosine residues on the transmembrane band-3 protein, have been isolated from human erythrocyte membranes and partially characterized by different laboratories, i.e. one extracted by non-ionic detergent (Triton X-100 or Nonidet P-40), the other solubilized by 0.25 M NaCl from the detergent-insoluble residue. The present paper shows that these two membrane-associated Tyr-protein kinases purified, in the presence of bovine serum albumin, by phosphocellulose chromatography followed by heparin-Sepharose chromatography, have the same apparent molecular mass (36 kDa) determined by Ultrogel Ac44 filtration. Moreover, both Tyr-protein kinases exhibit several identical properties, including Km values for band 3, the random acidic copolymer poly(Glu,Tyr)4:1 and angiotensin II, pH dependence, response to Mn2+ and Mg2+, response to NaCl and 2,3-bisphosphoglycerate. All these properties are identical or very similar to those exhibited by the Tyr-protein kinase previously isolated by us from human erythrocyte cytosol. These results suggest that the two membrane-associated and the cytosolic Tyr-protein kinase activities are mediated by the same enzyme, distributed between the cytosol and the membrane structures. PMID- 2920727 TI - Characterization of two murine (2'-5')(A)n-dependent endonucleases of different molecular mass. AB - RNase L is considered as the major if not unique target of (2'-5')(A)n and therefore as an important intracellular mediator of interferon action. It behaves as an 185-kDa species in various cell extracts when analyzed by gel filtration. SDS/PAGE analysis of the polypeptides covalently labelled with a (2'-5')(A)4-3' [32P]pCp probe reveals a single 80-kDa species, thus attesting a multimeric form of the 185-kDa protein. At variance with such data, mouse spleen extracts reveal an additional 40-kDa polypeptide with (2'-5')(A)n-dependent ribonucleolytic activity. This seemingly new form of RNase L migrates as a 40-kDa polypeptide when analyzed under native or denaturing conditions. It bears some structural similarity with the larger-molecular-mass RNase L as revealed by partial proteolysis. It is probably not generated through proteolytic degradation of the 185-kDa RNase L during extract preparation, although its physiological significance is unknown. Indeed various protease inhibitors do not significantly alter the ratio of 40-kDa and 185-kDa (2'-5')(A)n-dependent ribonucleases; moreover, the (2'-5')(A)n-binding capacity of the 40-kDa polypeptide is more stable than that of the 185-kDa one. PMID- 2920728 TI - Purification and properties of five different forms of human procarboxypeptidases. AB - Three different procarboxypeptidases A and two different procarboxypeptidases B have been isolated for the first time, in a pure and native state, from human pancreatic extracts. These proteins were purified in one or two quick steps by anion-exchange HPLC. All these forms have been biochemically characterized. Two of the procarboxypeptidases A, the A1 and A2 forms, are obtained in a monomeric state while the other, the A3 form, is obtained as a binary complex of a procarboxypeptidase A with a proproteinase E. This complex is stable in aqueous buffers at various ionic strengths and develops carboxypeptidase A and proteinase E activities in the presence of trypsin. The A1 and A2 forms show clear differences in electrophoretic mobility in SDS/polyacrylamide gels, isoelectric point, proteolytic activation process with trypsin and susceptibility to thermal denaturation. In contrast, these properties are similar in the A1 and A3 (binary complex) forms. On the other hand, with respect to the properties listed above, the B1 and B2 forms differ from each other mainly in isoelectric point. An overall comparison of the above properties reveals the unusual character of the A2 form, midway between the other A and B forms. N-terminal extended sequence analysis carried out on these proenzymes confirm that they constitute different isologous forms. PMID- 2920729 TI - Purification of nitrate reductase from Nicotiana plumbaginifolia by affinity chromatography using 5'AMP-sepharose and monoclonal antibodies. AB - Nitrate reductase was purified from leaves of Nicotiana plumbaginifolia using either 5'AMP-Sepharose chromatography or two steps of immunoaffinity chromatography involving monoclonal antibodies directed against nitrate reductase from maize and against ribulose-1,5-bisphosphate carboxylase from N. plumbaginifolia. Nitrate reductase obtained by the first method was purified 1000 fold to a specific activity of 9 units/mg protein. The second method produced an homogenous enzyme, purified 21,000-fold to a specific activity of 80 units/mg protein. SDS/PAGE of nitrate reductase always resulted in two bands of 107 and 99.5 kDa. The 107-kDa band was the nitrate reductase subunit of N. plumbaginifolia; the smaller one of 99.5 kDa is thought, as commonly reported, to result from proteolysis of the larger protein. The molecular mass of 107 kDa is close to the values calculated from the coding sequences of the two nitrate reductase genes recently cloned from tobacco (Nicotiana tabacum cv Xanthi). PMID- 2920730 TI - The carboxyltransferase activity of the sodium-ion-translocating methylmalonyl CoA decarboxylase of Veillonella alcalescens. AB - Methylmalonyl-CoA decarboxylase of Veillonella alcalescens catalyzed the isotopic exchange between methylmalonyl-CoA and [1-14C]propionyl-CoA or between malonyl CoA and [1-14C]acetyl-CoA. The exchange was independent of sodium ions and was abolished by avidin. The enzyme also catalyzed the carboxyl transfer reaction from methylmalonyl-CoA to acetyl-CoA yielding propionyl-CoA and malonyl-CoA, and vice versa. The beta subunit was dissociated from methylmalonyl-CoA decarboxylase by prolonged washing of the enzyme while bound via its biotin prosthetic group to monomeric avidin-Sepharose. The beta-chain-depleted enzyme was inactive as a methylmalonyl-CoA decarboxylase but retained carboxyltransferase activity. The beta subunits were specifically protected by Na+ ions from tryptic hydrolysis. Based on these and other observations the following functions may be assigned to the different polypeptide chains of methylmalonyl-CoA decarboxylase: carboxyltransferase (alpha), carboxybiotin-carrier-protein decarboxylase (beta), biotin carrier protein (gamma). The function of the delta chain is unknown. PMID- 2920731 TI - Synthesis of glycoconjugates derived from various lipopolysaccharides of the Vibrionaceae family. AB - Conjugation of simple ketoses (such as 3-deoxy-D-manno-2-octulosonic acid and N acetylneuraminic acid) and of various O-specific polysaccharides (from Aeromonas hydrophila and Aeromonas salmonicida) to the bifunctional spacer 1,6 hexanediamine, was achieved by reductive amination. The saccharide--1-(6-amino) hexane alkyamines obtained were converted into the corresponding isothiocyanate derivatives and coupled to the free epsilon-amino group of lysine residues of the protein carrier bovine serum albumin. In similar manner, the aldehyde group introduced by selective periodate oxidation into the partially O-deacylated lipopolysaccharide of Vibrio anguillarum was conjugated to 1,6-hexanediamine, converted into the corresponding isothiocyanate and covalently attached to bovine serum albumin. PMID- 2920732 TI - The energy-conserving nitric-oxide-reductase system in Paracoccus denitrificans. Distinction from the nitrite reductase that catalyses synthesis of nitric oxide and evidence from trapping experiments for nitric oxide as a free intermediate during denitrification. AB - 1. A Clark-type electrode that responds to nitric oxide has been used to show that cytoplasmic membrane vesicles of Paracoccus denitrificans have a nitric oxide reductase activity. Nitrous oxide is the reaction product. NADH, succinate or isoascorbate plus 2,3,5,6-tetramethyl-1,4-phenylene diamine can act as reductants. The NADH-dependent activity is resistant to freezing of the vesicles and thus the NADH:nitric-oxide oxidoreductase activity of stored frozen vesicles provides a method for calibrating the electrode by titration of dissolved nitric oxide with NADH. The periplasmic nitrite reductase and nitrous-oxide reductase enzymes are absent from the vesicles which indicates that nitric-oxide reductase is a discrete enzyme associated with the denitrification process. This conclusion was supported by the finding that nitric-oxide reductase activity was absent from both membranes prepared from aerobically grown P. denitrificans and bovine heart submitochondrial particles. 2. The NADH: nitric-oxide oxidoreductase activity was inhibited by concentrations of antimycin or myxothiazol that were just sufficient to inhibit the cytochrome bc1 complex of the ubiquinol--cytochrome-c oxidoreductase. The activity was deduced to be proton translocating by the observations of: (a) up to 3.5-fold stimulation upon addition of an uncoupler; and (b) ATP synthesis with a P:2e ratio of 0.75. 3. Nitrite reductase of cytochrome cd1 type was highly purified from P. denitrificans in a new, high yield, rapid two- or three-step procedure. This enzyme catalysed stoichiometric synthesis of nitric oxide. This observation, taken together with the finding that the maximum rate of NADH:nitric-oxide oxidoreductase activity catalysed by the vesicles was comparable with that of NADH:nitrate-oxidoreductase, is consistent with a role for nitric-oxide reductase in the physiological conversion of nitrate or nitrite to dinitrogen gas. 4. Intact cells of P. denitrificans also reduced nitric oxide in an antimycin- or myxothiazol-sensitive manner. However, nitric oxide was not detected by the electrode during the reduction of nitrate. Nitric oxide synthesis from nitrate could be detected with cells in the presence of very low concentrations of Triton X-100 which selectively inhibits nitric-oxide reductase activity. 5. Nitric oxide was detected as an intermediate in denitrification by including haemoglobin with an anaerobic suspension of cells that was reducing nitrate. The characteristic spectrum of the nitric oxide derivative of haemoglobin was observed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2920733 TI - Defective processing and binding of low-density lipoprotein receptors in fibroblasts from a familial hypercholesterolaemic subject. AB - The properties of the low-density lipoprotein (LDL) receptor were studied in skin fibroblasts from a homozygous familial hypercholesterolaemic subject, MM (MM cells), who exhibits a defect in the processing of the precursor form of the receptor. Despite the prolonged half-life of the precursor (3 h), essentially all was eventually processed to the mature form, which was degraded with a half-life of approximately 6 h. The receptor content of the MM cells, determined by radioimmunoassay, was slightly lower than normal and by immunoblotting it was estimated that 55% was present as the mature form at equilibrium. The mature receptor reached the cell surface and was internalized and recycled apparently normally, with about 60% accessible to pronase at any time. Immunoblotting, immunoassay and surface labelling with 125I all indicated that the cells contained twice as much surface receptor protein as would be expected from the binding of LDL. Maximum heparin-releasable LDL binding to MM cells was 20% of normal and the apparent affinity for LDL was reduced. The cells did not show the marked increase in affinity and reduction in binding exhibited by normal cells when cooled to 4 degrees C. Also, neither the apparent affinity of the receptors nor the maximum binding at 37 degrees C was greatly affected by an antibody that has been shown to reduce the affinity and halve the binding of normal cells. The results suggest that the mutation in the LDL receptor gene of these cells affected the ability of the receptors to bind LDL in a similar manner to the antibody, possibly by promoting aggregation of receptors on the cell surface, and halving the amount of LDL bound. PMID- 2920734 TI - Hemoglobin from the Antarctic fish Notothenia coriiceps neglecta. 1. Purification and characterisation. AB - Antarctic fishes live at a constant temperature of -1.8 degrees C, in an oxygen rich environment. In comparison with fishes that live in temperate or tropical waters, their blood contains less erythrocytes and hemoglobin. A study was initiated on the structure and function of Antarctic fish hemoglobin. The erythrocytes of the Antarctic benthic teleost Notothenia coriiceps neglecta, of the family Nototheniidae, have been shown to contain two hemoglobins, accounting for about 90% and 5% of the total content. These hemoglobins have been isolated, and obtained in crystalline form. They are tetramers and contain two pairs of globin chains. The globin chains of each hemoglobin have been purified and characterised. The two hemoglobins appear to have one of the two globin chains in common. The Root and Bohr effects have been investigated in erythrocytes, 'stripped' hemolysates and pure hemoglobins, indicating that the functional properties are finely regulated by pH and allosteric effectors. PMID- 2920735 TI - Hemoglobin from the Antarctic fish Notothenia coriiceps neglecta. 2. Amino acid sequence of the alpha chain of Hb1. AB - The complete amino acid sequence of the alpha chain of the main hemoglobin of the Antarctic fish Notothenia coriiceps neglecta (family Nototheniidae) has been determined. It consists of 142 residues; an acetylated seryl residue is at the amino terminal. The molecular mass is 15,519 Da. In comparison with alpha-chain sequences of non-Antarctic poikilothermic fish hemoglobins, the homology appears to be significantly lower than that existing among the latter species. A higher homology has been found with the alpha-chain sequence of the non-poikilothermic bluefin tuna. PMID- 2920736 TI - The influence of purification and protein heterogeneity on the crystallization of p-hydroxybenzoate hydroxylase. AB - The structure of the enzyme p-hydroxybenzoate hydroxylase was determined to a resolution of 0.25 nm [Wierenga et al. (1979) J. Mol. Biol. 131, 53-73] with crystals belonging to space group C222(1). Subsequently it was impossible to repeat the growth of this crystal form and only poor quality tetragonal crystals could be obtained. We have thoroughly investigated this problem and found that Cibacron-blue-purified enzyme appears to be heterogeneous with respect to aggregation state and Cys-116 oxidation. Most importantly, it could be firmly established that C222(1) crystals can only be grown from purely dimeric p hydroxybenzoate hydroxylase possessing an intact SH group. Ion-exchange chromatography on DEAE-Sepharose can successfully remove those forms of the enzyme which impede successful crystallization. Sulfite and dithiothreitol improve crystallization by dissociating the enzyme oligomers into dimers; sulfite especially gives excellent results. PMID- 2920738 TI - A survey and critical evaluation of a dual isotope (Dicopac) vitamin B12 absorption test. AB - The results of all dual isotope tests (2142) carried out on 1989 patients, 807 males (40.6%) and 1182 females (59.4%), during a 10 year period (1976-1985 inclusive) in the Grampian Health Board Area (population 497,272) have been reviewed. Patient age ranged from 5-95 years with 45.5% over 60 years. The referring specialties were Gastroenterology (47.6%), Haematology (11.3%), Paediatrics (2.1%) and all others (39.0%). According to the manufacturer's recommended criteria, results were classified as normal in 1054 (49.2%), abnormal in 659 (30.8%), equivocal in 337 (15.7%) and unsatisfactory in 92 (4.3%) tests. Vitamin B12 malabsorption of ileal type was indicated in 544 tests (25.4%) and of gastric type in 115 (5.4%). Of the latter, 76 were related to pernicious anaemia, 10 to previous gastric surgery and 2 to gastric carcinoma. Of the 337 patients with equivocal results, 138 patients were reviewed and 115 (83.3%) found to have a documented cause for gastric malabsorption (96 pernicious anaemia and 19 previous gastric surgery). In 172 patients with proven pernicious anaemia the manufacturer's recommended criteria for gastric malabsorption were completely satisfied in only 76 (44.3%) but 167 (96.5%) had an excretion ratio greater than or equal to 1.3 and 127 (73.8%) a ratio greater than or equal to 1.7. Unsatisfactory tests were mainly due to incomplete urine collection (91.3%) or contamination with another isotope (5.4%). PMID- 2920737 TI - The behavior of 99mTc-hexamethylpropyleneamineoxime (99mTc-HMPAO) in blood and brain. AB - 99mTc-hexamethylpropyleneamineoxime (99mTc-HMPAO) is a reagent for scanning cerebral blood flow. We investigated how 99mTc-HMPAO changed in the blood and brain. The 99mTc-HMPAO, which was prepared by adding of 99mTcO4- to HMPAO and Sn(II), consisted of primary and secondary complexes, reduced hydrolyzed 99mTc, and 99mTc-pertechnetate. The percentage of the primary complex in 99mTc-HMPAO decreased with time after preparation. The primary complex converted to the secondary one very rapidly in the presence of plasma. When 99mTc-HMPAO was injected into patients, 99mTc activity was immediately partitioned in the plasma fraction, with approximately 60% in whole blood. In plasma, 99mTc was found to be associated with proteins such as albumin and globulin. 99mTc trapped in red cells was not washed out with either plasma or saline. Biodistribution studies showed that the less lipophilic compounds of 99mTc-HMPAO could not pass through the blood brain barrier (BBB), and therefore did not accumulate in the brain. The results of gel chromatography and equilibrium dialysis indicated that no specific 99mTc binding protein was present in the brain. Considering the instability of 99mTc-HMPAO in vivo, we proposed that the speed at which the primary complex converted to the less lipophilic compounds was important in allowing 99mTc-HMPAO to pass through the BBB and to be fixed in the brain. PMID- 2920739 TI - [18F]fluorodeoxyglucose scintigraphy in diagnosis and follow up of treatment in advanced breast cancer. AB - Seventeen patients with advanced breast cancer were imaged with a specially collimated gamma camera to study tumor uptake of 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) before and during therapy. Fourteen patients (82%) showed increased FDG accumulation in metastatic tumors, 6/8 (75%) of axillary, supra or infraclavicular metastatic lymph nodes were detectable. In one of these cases, FDG imaging was the first method to identify axillary metastasis causing nerve compression. Also, pulmonary and liver metastases could be imaged with FDG; both in two patients. The intra individual variability in uptake was considerable in bone metastases, and some lesions remained FDG negative: 99mTc-DPD was superior in detecting bone disease. Bone metastases of the osteolytic or mixed type were better visualized than sclerotic ones. Ten patients were reimaged later to assess the effect of therapy on FDG uptake. Increased uptake was associated with clinical progression, while unchanged or diminished uptake did not predict the course of disease as reliably. This study indicates that FDG can be used to image breast cancer metastases. FDG may be valuable in monitoring treatment response, but positron emission tomography (PET) would probably be more appropriate than planar imaging for this purpose. PMID- 2920740 TI - Determinants of diagnostic accuracy in pulmonary scintigraphy for pulmonary capillary protein leak associated with adult respiratory distress syndrome (ARDS): a technical note. AB - Radionuclide assessment of pulmonary capillary protein leak using [99mTc] human serum albumin (99mTc-HSA) was first reported from our laboratory. In this study we investigated the impact of 1) sampling time post tracer injection, and 2) lung region assignment, on diagnostic accuracy between 2 groups (control n = 20 and ARDS n = 20). Each patient received 370 MBq 99mTc-HSA i.v. and was imaged for 45 min. The slope index (SI) [change in lung: heart activity ratio/min] was calculated from 11 computer assigned lung regions for intervals of 5-15 (early [E]) and 15-45 (late [L]) min. The diagnostic accuracy of E vs L SI calculations for the 11 regions was evaluated by stepwise logistic regression. E SI data and L SI data from the lower 1/3 of the lung did not achieve significance for inclusion in the discriminant model (P less than 0.05). In the nine remaining regions L SI was significant. Optimal discrimination was achieved from L SI data obtained from a region confined to the lateral half of the mid 3rd of the lung field (sensitivity 81%, specificity 85%, accuracy 83%). The results confirm that: 1) a late (15-45 min) sampling period and 2) proper region assignment are necessary to maximize accuracy of this technique. PMID- 2920741 TI - beta-Methyl-15-p-iodophenylpentadecanoic acid metabolism and kinetics in the isolated rat heart. AB - The use of 15-p-iodophenyl-beta-methyl-pentadecanoic acid (beta Me-IPPA) as an indicator of long chain fatty acid (LCFA) utilization in nuclear medicine studies was evaluated in the isolated, perfused, working rat heart. Time courses of radioactivity (residue curves) were obtained following bolus injections of both beta Me-IPPA and its straight chain counterpart 15-p-iodophenyl-pentadecanoic acid (IPPA). IPPA kinetics clearly indicated flow independent impairment of fatty acid oxidation caused by the carnitine palmitoyltransferase I inhibitor 2[5(4 chlorophenyl)pentyl]oxirane-2-carboxylate (POCA). In contrast, beta Me-IPPA kinetics were insensitive to changes in fatty acid oxidation rate and net utilization of long chain fatty acid. Analysis of radiolabeled species in coronary effluent and heart homogenates showed the methylated fatty acid to be readily incorporated into complex lipids but a poor substrate for oxidation. POCA did not significantly alter metabolism of the tracer, suggesting that the tracer is poorly metabolized beyond beta Me-IPPA-CoA in the oxidative pathway. PMID- 2920742 TI - Myocardial 201Tl washout after combined dipyridamole submaximal exercise stress: reference values from different patient groups. AB - Dipyridamole stress is favorable in patients unable to exercise maximally for 201Tl myocardial scintigraphy. Aside from an analysis of uptake defects, proper washout analysis can be limited by heart rate variations when isolated dipyridamole stress is used. Heart rate standardized 201Tl washout kinetics after a combined dipyridamole and submaximal exercise stress protocol (CDSE), feasible in elderly patients as well as in patients with peripheral artery disease, were therefore studied to investigate the 201Tl washout after CDSE in differently defined patient groups: Group I comprised 19 patients with documented heart disease and angiographically excluded coronary artery disease (CAD); group II contained 17 patients with a very low likelihood of CAD determined by both normal exercise radionuclide ventriculography and normal 201Tl uptake. Group III comprised 56 patients with a 50% pretest likelihood of CAD but normal 201Tl uptake. Mean washout values were nearly identical in all groups. Despite similar uptake patterns, however, washout standardized by CDSE was significantly lower than the normal washout values after maximal treadmill exercise. Thus an obviously lower 201Tl washout after CDSE than after maximal treadmill exercise must be considered if washout analysis criteria after dipyridamole are applied to evaluate ischemic heart disease. Nevertheless, heart rate elevation achieved by additional submaximal exercise stress seems necessary, adequate and clinically safe for standardisation of washout analysis in dipyridamole 201Tl scintigraphy. PMID- 2920743 TI - Automatic assignment of elliptical ROIs: first results in planar scintigrams of the left ventricle. AB - Several algorithms for quantitative analysis of 201Tl scintigrams require operator assigned elliptical regions. Therefore these algorithms are hampered by inter- and intra-observer errors. In this paper we present a robust algorithm to determine automatically contours with elliptical shapes. The algorithm is based on the Hough transformation and can determine the parameters describing an ellipse even in low signal-to-noise ratio images and when the contour is only partially visualized such as in non-perfused regions of the left ventricular myocardium. As long as the number of parameters to describe the shape of the contour is not too large, the same kind of algorithm can also be used for differently shaped contours, and for 3D elliptical contours as in SPECT. PMID- 2920744 TI - The diameter of coronary arteries in infants and children without heart disease. AB - Two-dimensional echocardiographic examinations of the proximal left and right coronary artery were performed in 100 children without heart disease. Fifty-nine boys and 41 girls were studied whose ages ranged from 1 day to 17 years old. The diameter of the proximal right and left coronary artery was 1 mm in newborns and 4.5 mm in teenagers. No significant difference was observed between male and female subjects. A linear correlation between the coronary artery dimensions and the patient's age, weight, length, and body surface area could be demonstrated. The closest linear correlation corresponded to the patient's length with a correlation coefficient of r = 0.91 and r = 0.89 for the right and the left proximal coronary artery respectively. A quick orientation concerning normality of coronary artery diameters is possible with our graph of body length and corresponding coronary artery size. Knowing normal echocardiographic values for proximal coronary artery diameters, even subtle changes of these vessels can be diagnosed and the number of invasive diagnostic procedures, e.g. in Kawasaki disease, can be reduced. PMID- 2920745 TI - High dose intravenous methylprednisolone for Kassabach-Merritt syndrome. AB - Kassabach-Merritt syndrome involving the sternum in a 2-month-old child is described. Treatment with high dose intravenous methylprednisolone resulted in normalization of the platelet count and disappearance of haemangioma. PMID- 2920746 TI - Recurrent parotid gland enlargement as an initial manifestation of Sjogren syndrome in children. AB - Recurrent parotid gland enlargement is a common disorder in children, while that of auto-immune aetiology is rare. Three children with recurrent parotid swelling had autoantibodies including antinuclear antibody, anti-SS-A (Sjogren syndrome A), SS-B (Sjogren syndrome-B) antibodies and rheumatoid factor, abnormal sialograms and lymphocytic infiltration of salivary glands, which were consistent with Sjogren syndrome. Initially, all three lacked symptoms of keratoconjunctivitis sicca. During follow up, two patients developed xerostomia and were diagnosed as having primary Sjogren syndrome. Recurrent parotid enlargement appears to be important as an initial manifestation of Sjogren syndrome in children. PMID- 2920747 TI - Infants born to mothers with antibodies against Borrelia burgdorferi at delivery. AB - A serological survey over a 1-year period of 1416 mothers at delivery and their 1434 offspring for the presence of anti-Borrelia burgdorferi antibodies revealed a prevalence of 0.85%. Clinically active Lyme disease during pregnancy was found in 1 of these 12 women with elevated titres and the child was born with a ventricular septal defect. Of six affected children, two had hyperbilirubinaemia, one muscular hypotonia, one was underweight for gestational age, one was macrocephalic, and one had supraventricular extrasystoles. Anomalous findings could not be attributed to B. burgdorferi due to a lack of serological evidence of intrauterine infection. Our data do not imply the need for serological screening in pregnancy, however, the importance of recognition and treatment of Lyme disease in pregnancy is emphasized. PMID- 2920748 TI - Meningitis due to Borrelia burgdorferi in the initial stage of Lyme disease. AB - Borrelia burgdorferi (B.b.) was isolated from cerebrospinal fluid from two children with aseptic meningitis. Serology for B.b. was initially negative or borderline and became positive during the subsequent course. Children with aseptic meningitis of unknown origin should be re-evaluated within 1 month to detect possible increasing antibody titres to B.b. Aseptic meningitis may be a stage 1 manifestation of Lyme disease. PMID- 2920749 TI - Unusual course of a Chlamydia pneumonia in an infant with IgG2/IgG4-deficiency. AB - An unusual case of Chlamydia trachomatis (C. trachomatis) pneumonia, complicated by the development of a pneumothorax, is reported in an IgG2/IgG4 deficient infant delivered by caesarean section. C. trachomatis was isolated initially from a throat smear and subsequently from pleural effusions. Serological examinations using the complement fixation test were negative in sera of both mother and child. However, using immunofluorescence the presence of an acute or recent infection was confirmed by IgM-antibodies in the serum of the infant and IgA antibodies in the serum of the mother. At the age of 7 months the girl suffered from impetigo contagiosa which was partially resistant to antibiotic treatment. IgG-subclass deficiency was diagnosed after the onset of this disease and the girl was then treated by immunoglobulin transfusion. PMID- 2920750 TI - Rubinstein-Taybi syndrome in a mother and son. AB - The Rubinstein-Taybi syndrome is a condition characterized by mental retardation, typical facial changes and broad thumbs and big toes. The cause is unknown; almost all cases are sporadic. We describe a mother and son with Rubinstein-Taybi syndrome. Literature search documented at least 413 cases with 558 sibs. An affected offspring has occurred at least twice, possibly six times. In 45 yet undescribed Dutch cases no recurrence was found in 94 sibs. A submicroscopic chromosome deletion seems the most probable explanation, but other alternatives may be possible. PMID- 2920751 TI - Postaxial acrofacial dysostosis or Miller syndrome. A case report. AB - A case of postaxial acrofacial dysostosis (Miller syndrome) is presented. This rare syndrome is essentially characterized by a Treacher-Collins-like facial appearance together with absence of the fifth digital ray of all limbs and variable forearm hypoplasia. PMID- 2920752 TI - Further evidence for infectious origin of isolated transient hyperphosphatasaemia. AB - Marked transient increases in serum alkaline phosphatase activity were found in three siblings with upper respiratory tract infections. This supports observations suggesting an infectious origin of the condition termed "transient hyperphosphatasaemia of infancy and early childhood". PMID- 2920753 TI - Low antithrombin III: accurate predictor of idiopathic respiratory distress syndrome in premature neonates. AB - A prospective study was performed in premature neonates to determine the predictive values of antithrombin III (AT III) deficiency immediately after birth, for the subsequent development of idiopathic respiratory distress syndrome (IRDS), intraventricular haemorrhage (IVH) and death. Of the 81 premature infants studied, 24 developed IRDS (30%). Of these 24 premature infants, 8 also developed IVH and 9 infants died within the follow-up period of 7 days. The mean plasma AT III level was significantly lower in the infants developing IRDS (0.23 U/ml vs 0.35 U/ml, P less than 0.0005). Within this study group 33 neonates of less than 30 weeks' gestation showed a prevalence for IRDS of 48%. In this group, AT III activity levels below 0.30 U/ml were 8.5 times as likely to result from infants with IRDS than from infants without IRDS. The diagnostic accuracy indices of criteria for the development of IRDS were: a sensitivity of 100%, a specificity of 88%, a positive predictive value of 89% and a negative predictive value of 100%. The predictive values for the development of IVH and occurrence of death were insignificant. Therefore, in premature neonates the combination of less than 30 weeks' gestation and an AT III below 0.30 U/ml is highly suggestive of IRDS and may facilitate the evaluation of early treatment. PMID- 2920754 TI - Primary infantile hypomagnesaemia; report of two cases and review of literature. AB - We describe two male infants suffering from primary hypomagnesaemia, diagnosed at 3 months and 2.5 months of age. They both presented with generalised convulsions, with case 2 exhibiting hypocalcaemia which did not respond to calcium and case 1 having normocalcaemia at first but hypocalcaemia 3 days after admission. Both improved dramatically after initiation of magnesium therapy. A carrier-mediated transport defect is the most likely cause of this disease. It is of the utmost importance that a correct and prompt diagnosis be made as therapy is simple and effective. Failure in diagnosing this condition could prove fatal as demonstrated in the family history of case 2. PMID- 2920755 TI - Neurogenic bladder due to herpes zoster infection in an infant. AB - A case is presented of Herpes zoster (HZ) infection in a 2.5-month-old infant with the added complication of a neurogenic bladder. The patient's mother suffered from varicella during the 18th week of pregnancy. The patient had a typical herpetic rash at the age of 2.5 months, and developed constipation and a neurogenic bladder. While the constipation improved, bladder atonicity led to hydroureters necessitating bilateral ureterostomies. Urinary tract involvement of HZ is well known in adults and is reversible. To our knowledge this is the first report of such a complication of HZ infection in infants. PMID- 2920756 TI - Congenital hypomyelination with axonopathy. AB - We report a case of congenital neuropathy taking a rapidly fatal clinical course. Ultrastructural features of the peripheral nerve were unusual with sparsity of myelinated fibres, lack of "onion bulb" formation and presence of axonal damage. This case is compared with previously reported cases of early infantile neuropathy. PMID- 2920757 TI - Vitamin D metabolism in tumoral calcinosis. PMID- 2920758 TI - New estradiol-linked nitrosoureas: can the pharmacokinetic properties help to explain the pharmacodynamic activities? AB - The pharmacokinetics of 1-(2-chloroethyl)-1-nitrosocarbamoyl-L-alanine-estradiol 17-ester (CNC-alanine-estradiol-17-ester) a new estradiol-linked anticancer drug and the unlinked DNA-crosslinking agent 1-(2-chloroethyl)-1-nitrosocarbamoyl-L alanine (CNC-alanine) have been studied in methylnitrosourea-induced female Sprague-Dawley rats after equimolar intravenous and oral administration. In comparison with the unlinked single agent, the CNC-alanine-estradiol-17-ester showed a 3-fold longer halflife in plasma and a three times larger volume of distribution. The distribution after intravenous administration was nearly three times faster. The absorption after peroral administration was likewise two times faster. The bioavailability of the estradiol-linked drug was determined to be 52%. After application of CNC-alanine-estradiol-17-ester the cytostatic metabolite CNC-alanine was found, indicating the cleavage of the ester bond. CNC alanine generated from CNC-alanine-estradiol-17-ester showed a 50% longer halflife than when applied directly. The results indicate that linking 2 chloroethyl-nitrosoureas to estradiol can result in new anticancer agents with modified properties in comparison to the unlinked single agent. The higher antineoplastic activity of the hormone-linked drug can mainly be attributed to differences in the pharmacokinetic behaviour. PMID- 2920759 TI - Evaluation of cardiac toxicity of idarubicin (4-demethoxydaunorubicin). AB - Cardiac toxicity of idarubicin (4-demethoxydaunorubicin), a new daunorubicin derivative, was tested in 49 phase II patients with advanced malignancies. In 26 patients the drug was given intravenously at a dose of 13 mg/m2 and in 23 orally at a dose of 45 mg/m2. Cardiac toxicity was evaluated by means of electrocardiography, left ventricular systolic time intervals, echocardiography and radionuclide cineangiography. The type and incidence of ECG abnormalities were comparable to those observed with other anthracycline analogs. Other functional parameters, serially measured to evaluate delayed cardiotoxicity in patients who received more than 65 mg/m2 intravenously or 225 mg/m2 orally, were not significantly different from pretreatment values. No patient developed clinical congestive heart failure. Only one patient exhibited a drop in the left ventricular ejection fraction of more than 15% from pretreatment values. These data indicate that idarubicin given orally or intravenously at the tested doses has no significant cardiotoxic activity in the range of the cumulative doses attained. PMID- 2920760 TI - A phase II study of high dose ifosfamide in metastatic colorectal cancer. PMID- 2920761 TI - A phase II trial of oral idarubicin plus dibromodulcitol in advanced breast cancer. PMID- 2920762 TI - Therapy of small cell lung cancer: the use of surgery. PMID- 2920763 TI - Prolactin and breast cancer. PMID- 2920764 TI - Effective systemic therapy for spinal epidural metastases from breast carcinoma. AB - A complete resolution of spinal epidural metastases following systemic therapy, consisting of chemotherapy and/or hormonal therapy, is reported in four patients with breast carcinoma. Remissions were of substantially longer duration than previous remissions induced by radiotherapy. Single systemic therapy is an underestimated way of treatment for spinal epidural metastases. This way of treatment should be considered when radiotherapy has failed. Under certain circumstances it might even be considered as primary treatment. The protracted remissions following systemic therapy, even in the case of a complete myelographic block, warrant further clinical studies concerning this mode of treatment. PMID- 2920765 TI - Changes in scalp hair after cancer chemotherapy. PMID- 2920766 TI - The effect of trifluoperazine, a calmodulin antagonist, on the growth of normal and malignant epidermal keratinocytes in culture. AB - Calmodulin, a cytoplasmic calcium binding protein, is present in concentrations two- to four-fold higher in malignant cells compared to normal cells. In an effort to learn the significance of these elevated levels, we examined the effect of calmodulin blockage on the growth of normal and malignant keratinocytes in vitro. The level of calmodulin in SCC12.B2, a line of keratinocytes derived from an epidermal squamous cell carcinoma (SCC), was about 3.5 times greater than in normal, human newborn foreskin keratinocytes. When exposed to trifluoperazine (TFP), an inhibitor of calmodulin, cell growth was reduced primarily in the cultures of normal keratinocytes. This growth inhibition resulted from two changes in the replicating population of cells, namely an increase in cell cycle length and an increase in rate of cell cycle withdrawal. Cell cycle withdrawal is the irreversible arrest of the cell cycle and is an early event in keratinocyte terminal differentiation. There was no measurable effect on the cell cycle time or withdrawal rate in SCC12.B2. The increased resistance to growth arrest in SCC cells may be a consequence of the elevated level of calmodulin in these cells. PMID- 2920767 TI - Clinical and radiological correlation of retroperitoneal metastasis from nonseminomatous testicular cancer treated with chemotherapy. AB - Forty patients with retroperitoneal metastasis from nonseminomatous testicular cancer treated with chemotherapy were retrospectively studied to (1) evaluate the predictive value of mass size as detected by computerized tomography (CT) as an indicator for postchemotherapy surgery and (2) determine the factors that influence relapse. Patients received two further courses of chemotherapy after their serum biomarkers became normal and computed tomography indicated a complete response or presence of a residual but stable mass. We found that patients with initial metastases less than 2 cm had a low frequency (14%) of residual masses after chemotherapy, vs. 59% for those with masses of 2-5 cm and 75% for those with masses of greater than 5 cm (P = 0.03). Of 22 patients with primary embryonal carcinoma, three of seven (43%) with residual masses after chemotherapy had mature teratoma at surgery. Six patients had small (1-2 cm) residual abnormalities that were not removed, and three of these patients relapsed. In conclusion, increasing size of retroperitoneal metastasis by CT scan predicts for increased likelihood of a residual mass after chemotherapy; patients who have a residual mass greater than or equal to 1 cm require retroperitoneal lymphadenectomy after chemotherapy, whether the tumor histology is embryonal carcinoma or teratoma. The role of surgery for patients who have residual retroperitoneal masses less than 1 cm after chemotherapy could not be determined from our study. PMID- 2920768 TI - Factors at presentation influencing the prognosis in breast cancer. AB - Presentation data on 607 breast cancer patients treated by a variety of modalities at Guy's Hospital, London, have been analysed using the Cox proportional hazards model, to identify factors associated with length of overall survival. When deaths attributable to causes other than breast cancer were treated as censoring events, the significant factors were found to be stage, mode of treatment, menstrual status and tumour size. The analysis was repeated for the subgroup of 326 patients treated by modified radical mastectomy. Four variables: stage, age at menarche, menstrual status and age were found to be significantly associated with both overall survival and length of distant recurrence-free interval. These factors have been combined to create a prognostic index which has been used to define subgroups of patients with different prognosis. The index has been validated on a separate group of 457 modified radical mastectomy patients treated at the same hospital. PMID- 2920769 TI - Analysis of glycoproteins released from benign and malignant human breast: changes in size and fucosylation with malignancy. AB - Radiolabelled glycoproteins released into media from benign and malignant human breast tissue after 48 h organ culture have been analysed using SDS polyacrylamide gel electrophoresis and fluorography. Major differences were identified between benign and malignant tissues: (i) a considerably higher incidence of glycoproteins in the molecular weight range 210-280 kDa detected from carcinomas than benign samples, with incidence being greater in poorly differentiated tumours; (ii) fucosylation of these glycoproteins released from carcinomas but not benign breast; (iii) heterogeneity, particularly of fucosylation, between the carcinomas but consistency amongst benign breast. A glycoprotein of MW 230 kDa was of particular interest since it was not detected from any benign samples but was present in 11 of 17 carcinomas, when it was almost always fucosylated. This could prove to be a useful tumour marker. PMID- 2920770 TI - The relationship between the unmodified initial tissue pH of human tumours and the response to combined radiotherapy and local hyperthermia treatment. AB - The relationship between unmodified tumour pH before treatment and tumour response was investigated in patients receiving combined radiotherapy and local hyperthermia treatment. Tumour pH showed a statistically significant positive correlation with the response rate (Spearman correlation coefficient 0.31, n = 50, 2P less than 0.05). The mean pH of tumours showing a complete response (CR) was significantly higher than that of tumours showing a partial response (PR) as well as those showing no change (NC). As the means of the PR and NC groups were not significantly different from each other, these groups were combined for further analysis. The pH of the CR group was also significantly different from that of the NC + PR group (CR: 7.36 +/- 0.05, median 7.36, n = 18, NC + PR: 7.16 +/- 0.06, median 7.21, n = 32); Mann-Whitney test: 2P less than 0.05). Stratification of the data with respect to radiotherapy dose, hyperthermia dose or tumour volume showed that these factors were not associated with tumour pH to such a degree that they might have seriously biased the results. The results suggest that enhancement of the cytotoxic effects of hyperthermia by low pH known from experiments with cell cultures is not observed in tumours which are treated with radiotherapy and hyperthermia, and that even the converse may occur. The reasons for this are discussed at length and it is suggested that sudden modification of the tumour pH directly prior to or during treatment is imperative to obtain any sensitizing effect. PMID- 2920771 TI - Protective effect of oral cysteamine against induction of gastric cancer by N methyl-N'-nitro-N-nitrosoguanidine in Wistar rats. AB - The effect of oral administration of cysteamine (2-aminoethanethiol hydrochloride) on the incidence and histology of gastric adenocarcinomas induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was investigated in inbred Wistar rats. Oral administration of 0.4% cysteamine in food after treatment with MNNG for 25 weeks significantly reduced the incidence and number of adenocarcinomas of the glandular stomach in experimental Week 52. Histological examination showed that adenocarcinomas that did develop in rats fed on cysteamine had high mucin producing activity. Furthermore, oral administration of cysteamine caused a significant increase in serum gastrin level and significant decreases in the antral mucosal pH and the labeling indices of the antral mucosa. These findings indicate that cysteamine inhibits the development of gastric adenocarcinomas when given orally. This effect may be related to its ability to decrease proliferation of antral mucosal cells. PMID- 2920772 TI - Chronic diazepam treatment produces regionally specific changes in GABA stimulated chloride influx. AB - GABA-stimulated 36Cl- influx was used to investigate regional differences in response to chronic diazepam treatment by comparing cortical and cerebellar tissue from rats chronically treated with diazepam for 3 weeks. Using a treatment protocol which has previously been shown to produce behavioral tolerance and physical dependence, cortical membrane preparations from chronic diazepam-treated rats were found to exhibit a decreased responsiveness to the stimulation of 36Cl- influx by GABA and a corresponding decrease in the ability of flunitrazepam to enhance GABA-stimulated 36Cl-influx. This decrease in sensitivity to flunitrazepam, however, appears to reflect the underlying decrease in sensitivity to GABA. In contrast, in membrane vesicles prepared from cerebella of chronic diazepam-treated rats, there was no measurable effect on GABA-stimulated 36Cl- influx or on the enhancement of GABA-stimulated 36Cl- influx by flunitrazepam. These results support the suggestion that there is a regionally specific reduction in GABA/benzodiazepine receptor function following chronic benzodiazepine treatment. PMID- 2920773 TI - RU 24722, a new eburnamine derivative, induces selective alterations in cerebral glucose utilization in freely moving rat. AB - The effect of a new eburnamine derivative, RU 24722, a putative phasic activator of catecholaminergic systems on local cerebral glucose utilization was studied in freely moving rats 15 min, 90 min and 6 h after the intraperitoneal administration of the drug (25 mg/kg). Of the 53 brain regions examined, 9 exhibited significant time-dependent increases of glucose utilization (up to 45 55%). Some changes were early and transient, as in the substantia nigra reticulata and the paraventricular nuclei. Other areas showed sustained (median septal nucleus) or delayed increases of glucose utilization (lateral septum, dorsal subiculum, hippocampal fimbria, fronto-parietal motor cortex and ventral cochlear nucleus). No significant alterations of glucose utilization could be elicited in the locus coeruleus and raphe nuclei, and none of the brain regions showed a decrease in glucose consumption. Our findings suggest that RU 24722 preferentially stimulates the activity in some brain areas involved in cognitive, vegetative and locomotor functions. PMID- 2920774 TI - Influence of age on calcium entry blocking drugs in rat aorta is spasmogen dependent. AB - On rat aorta, diltiazem (0.2 microM) caused parallel shifts in the Ca2+ concentration-response curves (K+-depolarized preparations). In aged (greater than 19 months) rats, this shift (0.57 log units) was smaller than in young (2 months) rats (1.04 log units) indicating an age-related reduction in the potency of diltiazem. Felodipine (10 nM), like diltiazem (1 microM) in a previous study, depressed the maximum response to noradrenaline more in preparations from aged rats (40% reduction) than from young rats (14% reduction). This increase in the effect of felodipine or diltiazem vs. noradrenaline reflected a reduction in the alpha-adrenoceptor reserve for noradrenaline. Accordingly, the depression in the maximum responses to other spasmogens (5-HT or K+) by 1 microM diltiazem was not increased by age (5-HT, young 59%, aged 49% reduction; K+, young 65%, aged 70% reduction). This aging can have two opposing influences on the effects of Ca2+ entry blocking drugs on rat aorta - a decrease in potency, yet an increase in effectiveness against spasmogens with a reduced receptor reserve. PMID- 2920775 TI - Antiinflammatory action of salicylates: aspirin is not a prodrug for salicylate against rat carrageenin pleurisy. AB - A current hypothesis postulates that the antiinflammatory effect of aspirin (acetylsalicylic acid) is mediated by its metabolite salicylic acid through inhibition of PGE2 synthesis. We tested this hypothesis in rats with carrageenin induced pleurisy. Aspirin or salicylate, given orally, reduced exudation and cell migration into the pleural cavity, aspirin being more potent than salicylate. The antiinflammatory effect of aspirin cannot be explained only in terms of salicylate formation. Doses of aspirin and salicylate that inhibit inflammation by 50% result in salicylate levels in the exudate of 70 +/- 12 and 323 +/- 17 micrograms/ml, respectively. At a significant antiinflammatory dose (100 mg/kg), salicylate did not reduce the prostaglandin and thromboxane content of the exudate. This indicates that inhibition of cyclooxygenase is not a likely mechanism for the antiinflammatory effect of salicylate. Salicylate only reduced the amount of 6-keto-PGF1 alpha in the exudate at higher doses (200 mg/kg), while aspirin at an equally antiinflammatory dose (50 mg/kg) reduced the content of 6 keto-PGF1 alpha, TXB2, PGD2 but not of PGE2 in the exudate. It therefore seems unlikely that an inhibition of PGE2 synthesis is the common mechanism by which aspirin and salicylate exert their antiinflammatory effects. These results do not supported the hypothesis that aspirin is a prodrug for salicylate but rather indicate that both compounds may exert their antiinflammatory effects partly by different mechanisms. PMID- 2920776 TI - Central muscarinic involvement in cardiovascular control in sinoaortic-denervated rats. AB - A study was made of the cardiovascular effects of centrally administered cholinergic drugs in conscious sham-operated or sinoaortic-denervated (SAD) rats. Neostigmine (0.01-1 micrograms) and bethanechol (0.125-2 micrograms), injected intracerebroventricularly (i.c.v.), induced a dose-dependent increase in mean blood pressure. This effect was significantly greater in SAD rats than in sham operated rats. The heart rate was reduced by both neostigmine and bethanechol in sham-operated rats but remained unaltered in SAD animals. Similar doses of neostigmine and bethanechol injected i.v. did not have an effect in sham-operated rats. Central muscarinic blockade with methylatropine (1 or 5 micrograms i.c.v.) prevented the cardiovascular effects induced by neostigmine (1 microgram i.c.v.) in both groups of rats. The administration of methylatropine (0.3 mg/kg i.v.) to sham-operated rats only prevented the bradycardia induced by neostigmine (1 microgram i.c.v.), the pressor response was not affected. These results lend support to the view that cholinergic pathways are involved in the pressor and bradycardic responses of sham-operated rats and that they are mediated through central muscarinic receptors. The bradycardia induced by lower doses of the anticholinesterase, neostigmine, cannot be reflex-mediated. The fact that the pressor response to neostigmine was higher in SAD rats than in sham-operated animals could be either due to a different activity of the cholinergic pathways or to an abolition of baroreflex afferent activity. These results also suggest that there is a connection between central cholinergic pathways and baroreflex efferent activity. PMID- 2920777 TI - Circadian rhythm of the in vitro stimulation of adenylate cyclase in rat heart tissue. AB - Adenylate cyclase activity in rat heart ventricles displayed a circadian rhythm with a maximum around 8:00 h and a minimum around 20:00 h. In vitro stimulation with 0.1 mM of isoprenaline, Gpp(NH)p or forskolin increased the 24-h-mean basal adenylate cyclase activity by 1.7-, 2.7- and 10.7-fold, respectively. The magnitude of the drug-induced stimulation varied significantly with the time of day. However, the drugs did not affect the timing of the circadian maximum or the amplitude (as % of 24-h-mean) of the basal rhythm. The data are the first to show that the response to the in vitro stimulation of the cardiac adenylate cyclase also displays a pronounced circadian rhythm. PMID- 2920778 TI - K+ channels openers prevent epilepsy induced by the bee venom peptide MCD. PMID- 2920779 TI - Protein composition of human aqueous humor: SDS-PAGE analysis of surgical and post-mortem samples. AB - We analyzed the protein composition of human aqueous humor. Samples were obtained by paracentesis from 25 human eyes (age range 64-92 years) at elective cataract surgery, and from 20 age-matched post-mortem eyes within 1.5 to 18 hr after death. Individual samples were assayed for total protein, and the polypeptides were separated by qualitative SDS-PAGE into high-, medium- and low-molecular weight ranges and then silver-stained. The clinical samples showed a remarkable consistency in the total protein values (mean +/- SEM: 12.4 +/- 2.0 mg per 100 ml) and no detectable variations in the profiles of the silver-stained proteins. Twelve major protein fractions, with apparent molecular weights of 140, 80 (doublet), 67, 60 (doublet), 35, 27, 25, 17, 14.6 and 9 kDa, were present. A preliminary analysis showed that the 17 kDa band contained a molecule resembling basic fibroblast growth factor. Two additional samples of aqueous humor from patients whose blood/aqueous barrier was compromised during paracentesis showed a quantitative and qualitative increase in the polypeptides that were present. Compared with the samples of aqueous humor obtained at surgery, the post-mortem samples exhibited a greater variability in total protein content (56.1 +/- 11.6 mg per 100 ml) and an increased number of high- and low-molecular-weight protein fractions. In view of wide differences in the clinical parameters, including ocular and systemic medications, systemic illness, surgical premedications, anesthesia and total serum protein values, the similarity in the protein profiles of the carefully drawn surgical samples is most remarkable. Our results indicate that, in patients who underwent elective cataract surgery, the levels of major proteins in human aqueous humor are not affected by wide individual variations in the clinical parameters. We attribute this finding to the care taken in the collection of aqueous humor samples. PMID- 2920780 TI - A rabbit lens epithelial cell line supports expression of an exogenous crystallin gene characteristic of lens fiber cell differentiation. AB - Cell lines derived from the lens generally fail to maintain synthesis of crystallins in long-term culture. Here we demonstrate that the N/N1003A line of undifferentiated lens epithelial cells, derived from a newborn rabbit, does not produce detectable levels of alpha-, beta- or gamma-crystallin transcripts, yet is capable of supporting the transient expression of the mouse gamma 2-crystallin promoter, a promoter which is active only in terminally differentiated lens fiber cells in vivo. Analysis of a set of deletion constructs suggested that sequences required for activity of the mouse promoter in N/N1003A cells are similar, but not identical, to those previously shown to be essential in primary chick embryo lens explants. Therefore, these results suggest that different transcriptional factors may be capable of supporting lens-specific activity of the mouse gamma 2 promoter. In addition, this cell line, N/N1003A, should be useful for investigations on the elements regulating gamma-crystallin gene expression. PMID- 2920781 TI - Immunomicroscopical study of type VI collagen in the trabecular meshwork of normal and glaucomatous eyes. AB - Cross-strained fiber bundles called long-spacing collagen or curly collagen occur in normal eyes in the trabecular meshwork. It can be seen in the basement membrane of the trabecular lamellae, in the sheath of the elastic-like fibers and underneath the inner wall of Schlemm's canal, where it forms part of the so called plaque material. The amount of this long-spacing collagen increases with age and is significantly more pronounced in glaucomatous eyes. Using immunohistochemical and immuno-electronmicroscopic methods, we have been able to show that type VI collagen is present in the aggregates called long-spacing collagen. PMID- 2920782 TI - The effects of aging and cataract formation on the trypsin inhibitor activity of human lens. AB - Assays were carried out to determine the trypsin inhibitor activity present in the water-soluble and water-insoluble fractions of human lenses of various ages. Little change was seen in the inhibitor activity of the water-soluble protein fraction. When this fraction was chromatographed on an Agarose A-1.5 m column, however, the inhibitor activity was increasingly associated with the high molecular weight (HMW) protein fraction with age. A gradual increase in water insoluble inhibitor was seen up to age 60, which correlated with the increase in protein in this fraction. After age 60, a marked increase in the water-soluble inhibitor activity was observed. In 80-90-yr old lenses, 1 mg of water-insoluble protein was able to inhibit 200 micrograms of crystallin trypsin by 50%. Similar assays on a collection of cortical and brunescent cataracts also showed very high levels of water-insoluble inhibitor activity. In most cases, these values were higher than those for the age-matched control lenses. Fractionation of the water insoluble proteins showed that the bulk of the activity remained with the urea insoluble fraction in cataractous lenses. A low molecular weight trypsin inhibitor was isolated from the water-soluble and water-insoluble fractions of human lenses. An age-dependent increase in this inhibitor was observed by activity measurements and electrophoretic analysis. PMID- 2920783 TI - Nucleotide levels in human lens: regional distribution in different forms of senile cataract. AB - Sensitive high-performance liquid chromatography methods were employed to assess regional distribution of adenine, guanosine and uridine nucleotides in clear and cataractous human eye lenses. According to slit-lamp examination, three forms of senile cataract were distinguished: (1) supranuclear or deep cortical cataract (typical senile cataract), (2) primary nuclear cataract (cataracta brunescens) and (3) subcapsular cortical cataract associated either with a supranuclear (3a) or a secondary nuclear cataract (3b). Except for AMP, which was highest in the nuclear fraction, all other nucleotides (ATP, ADP, GTP, and UTP) were predominantly located in the anterior cortex (plus epithelium) of clear as well as cataractous lenses, that is, ATP levels in the nucleus amounted to 20% of those found in the anterior cortex (plus epithelium); ATP levels in the posterior cortex were about 60% of those in the anterior cortex (plus epithelium). Significant differences in the absolute regional nucleotide level existed between the different forms of cataract. Highest ATP levels were found in the anterior cortex (plus epithelium) of clear lenses and deep or supranuclear cortical cataract. The ATP level was slightly diminished in primary nuclear cataract and in supranuclear cortical cataract when associated with an early subcapsular cortical cataract. ATP levels were depressed to less than 30% in the anterior cortex (plus epithelium) of lenses with a subcapsular cortical cataract when associated with either an early secondary nuclear or a mature cataract. Furthermore, the ATP/ADP ratio was decreased in this form of senile cataract. The decrease in lens nucleotide level did not correlate with increased age. These data suggest that decreases in regional ATP level are a secondary event and do not appear to be causally involved in the genesis of the 'cataracta senilis'. PMID- 2920785 TI - Development of tight junctions in the human ciliary epithelium. AB - Using the freeze-fracture technique, the tight junctions of the human ciliary epithelium were studied from 8 to 24.5 weeks of gestation with regard to their ability to act as a barrier to tannic acid. Zonular tight junctions were present as early as the 8th week of gestation, even before the emergence of ciliary folds, and they constituted an effective barrier to tannic acid at all stages studied. In the earliest stages, intramembranous particles were observed on the crest of membrane elevations, at regions of the future tight junctions. Discontinuous and loose networks of tight junctional strands were also encountered, indicating the formation of tight junctions. After the 10th week of gestation, ciliary folds developed and the configuration of the tight junctional networks underwent important changes. The apico-basal thickness of the junction, the number of superimposed strands, and the number of anastomoses decreased, while the number of complex strands increased. At the same period, junctional elements tended to become arranged in parallel lines. Steps which may lead to the formation of the tight junctions and the possible significance of the morphological modifications are discussed. PMID- 2920784 TI - Lysophospholipase and the metabolism of lysophosphatidylcholine in isolated bovine rod outer segments. AB - Incubation of bovine rod outer segments (ROS) with radiolabeled palmitic acid (16:0) and lysophosphatidylcholines (lysoPC) radiolabeled in either the fatty acid or the choline group indicated the presence of a lysophospholipase activity that is unaffected by Ca2+. In the presence of ATP, Mg2+ and CoA and acyl CoA:lysophospholipid acytransferase activity is evident, and free fatty acids, including those released by lysophospholipase activity, are esterified to membrane phospholipids. At low concentrations of lysoPC, 68% of it is acylated to form phosphatidylcholine (PC) and 24% is converted to glycerophosphocholine (GPC) and fatty acid per hour. As the concentration of lysoPC increases lysophospholipase activity increases, acyl-CoA:lysophospholipid acyltransferase activity decreases, and the proportion of lysoPC converted to PC decreases. The rate of production of lysophospholipids in vitro under phospholipase A stimulatory conditions exceeds the rate at which it can be removed by 5-10-fold. This suggests the possibility that an early step in light, anoxia- or hypoxia induced damage to photoreceptor cells may be activation of the phospholipase A endogenous to ROS. PMID- 2920786 TI - The fine structure of vascular-astroglial relations in transplanted fetal neocortex. AB - The vascular development within allografts of rat fetal neocortex was examined ultrastructurally with particular attention to astroglial-endothelial relationships. Grafts placed in the fourth ventricle exhibited a progressive astrogliosis around the host pial or choroidal vessels incorporated within the transplant which was evident by 1 month postoperative. Immunostaining with antisera to laminin showed intense reactivity around such neovessels at the light microscopic level. Transplants located intraparenchymally within the host parietal cortex also developed reactive astroglial "cuffs" around their marginal vessels by 1 week postoperative, although the degree and location of this reaction varied considerably with time. The origin of the reactive astroglia could not be directly determined from this study, but it is possible that they were stimulated by the collagen and fibroblasts present around vascularizing host pial and choroidal vessels in intraventricular grafts and by meningeal elements that entered the wound created for the intraparenchymal grafts. The marked astroglial reactivity within the grafts raises issues concerning their metabolic activity and their intimate relationship with brain endothelium. The close proximity of reactive astroglia to the graft vasculature would not appear to enhance the blood-brain barrier capabilities of transplant neovasculature, especially in intraventricular transplants, as might be suggested by many in vitro studies. PMID- 2920787 TI - Interactions between donor and host tissue following cross-species septohippocampal transplants. AB - Interactions between donor and host tissues following xenogeneic transplantation were studied using the neural cell surface antigen, Thy 1.2, as a marker for the donor tissue. Dissociated septal cells from Thy 1.2-positive fetal mice were transplanted to the dentate gyrus of Thy 1.2-negative adult rats. At post transplantation survival times between 1 and 5 months, an antibody to Thy 1.2 was used to identify donor tissue. The results demonstrate that the donor tissue was capable of migrating and developing within the host following transplantation. Thy 1.2-positive cells and processes were consistently found within the supragranular, infragranular, and molecular layers of the dentate gyrus, and occasionally within the hilus, suggesting that mechanisms existed within the host which influenced the development of the transplanted tissue. Additionally, the survival and growth of the Thy 1.2-positive neurons differed from previous reports describing the growth of acetylcholinesterase (AChE)-positive fibers from xenogeneic transplants. This finding suggested that in addition to growing within the host, xenogeneic transplants may also stimulate a compensatory sprouting response from the host. PMID- 2920788 TI - Immunological reactions induced by intracerebral transplantation: evidence that host microglia but not astroglia are the antigen-presenting cells. AB - The immunological reactions to embryonic cerebellar xenografts (n = 16) and allografts (n = 8) in host rat brain were studied after 2, 4, and 6 weeks of survival and compared to a control group consisting of 10 rats with isografts. Indirect immunofluorescence was performed on fresh frozen brain sections using antibodies against antigen presenting cells (Ia/Ox-6+ cells) and T helper (W3/25+) cells. Massive infiltrations of both cell types were found within xenografts. Ia antigen was present in the walls of small vessels near the transplant as well as in the ventricles on supra- and subependymal cells. In host tissue surrounding the grafts, Ox-6+ immunoreactivity was also observed in a population of cells ranging from an irregular rod-like shape with short branching processes to more rounded cell bodies with retracted processes. The appearance of these cells was characteristic of microglia. These cells were GFAP-negative. These cellular reactions were associated with rejection of the grafts. In contrast, the allografts survived, but nevertheless cells expressing Ox-6+ and to a lesser extent W3/25+ immunoreactivity were found along the injection needle tract and in damaged host tissue surrounding the grafts. No Ox-6+ perivascular infiltrations were seen. Some staining was also found within the allografts, mainly associated with damaged tissue. Ox-6+ ramified cells were also observed. Both Ox-6+ and W3/25+ immunoreactivity decreased with the time of survival. Host and donor GFAP-positive astrocytes did not express Ox-6+ molecules, and therefore probably were not involved in presenting antigen to effector cells. The control isografts also survived very well, but nevertheless Ox-6+ and less widespread W3/25+ cells were present in surrounding injured host tissue. Ox-6+ perivascular infiltration was not found in the host brain of animals with isografts. Ox-6+ and W3/25+ immunoreactivities were present primarily in graft areas that appeared damaged, often closely associated with injured host tissue. These results indicate that the process of implantation of grafts and associated brain injury induces enhanced Ia/Ox-6+ immunoreactivity, primarily on microglia in brain parenchyma surrounding grafts, and suggest that host microglia may substantially contribute to the initiation of immune reactions against intracerebral grafts. Despite this predisposition to an immunological response, only in the case of xenografts did these reactions, with the addition of Ox-6+ perivascular cuffing and cell infiltrations within the grafts, lead ultimately to graft rejection. PMID- 2920789 TI - Controlled release of dopamine from a polymeric brain implant: in vitro characterization. AB - A biocompatible polymeric matrix system for the long-term controlled release of dopamine has been developed. Solid particles of this bioactive agent were encapsulated in ethylene-vinyl acetate copolymer (EVAc). Following immersion in an aqueous buffer solution, the release rate of dopamine from the polymer matrix was found to depend on the initial concentration of dopamine in the polymer. After coating the matrix devices with an additional impermeable layer of EVAc, constant rates of release were obtained by creating a cavity in this impermeable layer. The observed experiments are consistent with a diffusion-limited model of dopamine release; all the in vitro experimental results were therefore correlated by the effective diffusion coefficient of dopamine through the porous polymer network. These results are discussed in terms of potential design modifications to achieve desired release characteristics for a variety of neuroactive substances, including neurotransmitters or their precursors. PMID- 2920790 TI - Parallel development of noradrenergic innervation and cellular compartmentation in the rat spleen. AB - By combining neurochemical measurement of norepinephrine (NE) with double-label immunocytochemistry for tyrosine hydroxylase-positive (TH+) noradrenergic nerves and specific lymphoid markers, we have examined the developmental compartmentation of noradrenergic nerves in the rat spleen. TH+ nerve fibers were present in the white pulp of the spleen at birth, among surface IgM-positive (sIgM+) B lymphocytes at the outer border of the periarteriolar lymphatic sheath (PALS), distant from the central artery. During the first 7 days, noradrenergic innervation developed rapidly, forming plexuses of nerve fibers along the central artery and its branches, among T and B lymphocytes of the PALS, and along the developing marginal sinus where ED3+ macrophages accumulate. The splenic concentration of NE (per mg wet wt.) and 3-methoxy-4-hydroxy-phenetheleneglycol (MHPG), a NE metabolite, increased rapidly during this period, suggesting that NE is available and released from these nerves. From 7-14 days, the white pulp expanded to include an inner PALS, outer PALS, marginal sinus, and marginal zone; during this period, TH+ fibers arborized principally among T lymphocytes of the inner PALS and adjacent to macrophages along the marginal sinus. By 14 days of age, NE concentration reached adult levels, although the MHPG/NE ratio (an index of NE turnover) remained higher throughout development than in adulthood. Finally, from 14-28 days, the outer PALS expanded to include follicles containing sIgM+ B lymphocytes. At the earliest stages of follicular development, a parafollicular rim of noradrenergic fibers was present, providing occasional branches which arborized within the follicle. No further changes were observed in either noradrenergic innervation or cellular compartmentation after 28 days of age. These findings suggest that noradrenergic fibers are present in developing compartments of the spleen at the earliest stages of their development, providing norepinephrine for interaction with a variety of adrenoceptor-bearing lymphoid and nonlymphoid cells. PMID- 2920791 TI - Sensory nerve crush and regeneration and the receptive fields and response properties of neurons in the primary somatosensory cerebral cortex of cats. AB - Extracellular recordings were made of activity evoked in neurons of the forepaw focus of somatosensory cerebral cortex by electrical stimulation of each paw in control cats and cats that had undergone crush injury of all cutaneous sensory nerves to the contralateral forepaw 31 to 63 days previously. Neurons responding only to stimulation of the contralateral forepaw were classified as sa; neurons responding to stimulation of both forepaws were classified as sb; neurons responding to stimulation of both contralateral paws were classified as sc; and neurons responding to stimulation of at least three paws were classified as m. The ratio sa:sb:sc:m neurons was 46:3:0:0 in control cats and 104:15:3:26 in cats that had undergone nerve crush 1-2 months prior to study. sa neurons from experimental cats had depth distributions similar to those in controls and responded to contralateral forepaw stimulation with more spikes per discharge, longer latency, and higher threshold than sa neurons in control cats. m neurons from experimental cats were distributed deeper in the cortex than sa neurons, and, when compared to experimental sa neurons, they responded with longer latency and poorer frequency-following ability; however, the number of spikes per discharge and threshold were not significantly different. The appearance of wide field neurons in this tissue may be explained in terms of strengthening of previously sub-threshold inputs to neurons in the somatosensory system. If the neurons in sensory cortex play a requisite role in cutaneous sensations and if changes similar to those reported here occur and persist in human cortex after nerve crush, then "complete" recovery of sensation in such patients may occur against a background of changed cortical neuronal responsiveness. PMID- 2920792 TI - Regional cerebral incorporation of plasma [14C]palmitate, and cerebral glucose utilization, in water-deprived Long-Evans and Brattleboro rats. AB - Regional rates of incorporation into brain of intravenously administered [14C]palmitate and regional cerebral metabolic rates for glucose (rCMRglc) were measured in water-provided (WP) and water-deprived (WD) homozygous (DI) and heterozygous (HZ) Brattleboro rats, a mutant strain unable to synthesize vasopressin, and in the parent Long-Evans (LE) strain. Following 15 h or 4 days of water deprivation, rCMRglc was elevated threefold in the pituitary neural lobe of LE-WD and DI-WD as compared with LE-WP rats, and in the paraventricular nucleus of LE-WD, and the supraoptic nucleus of DI-WD rats. However, incorporation of [14C]palmitate into these regions was not specifically altered. The results indicate that water deprivation for up to 4 days increases rCMRglc in some brain regions involved with vasopressin, but does not alter [14C]palmitate incorporation into these regions. Incorporation of plasma [14C]palmitate is independent of unlabeled plasma palmitate at brain regions which have an intact blood-brain barrier, but at nonbarrier regions falls according to saturation kinetics as cold plasma concentration rises, with a mean half-saturation constant (Km) equal to 0.136 mumol.ml-1. PMID- 2920793 TI - Prolongation of twitch potentiating mechanism throughout muscle fatigue and recovery. AB - Measurements have been made of twitch amplitudes in human ankle dorsiflexor muscles during and following fatiguing electrical stimulation. In six subjects, studied with the arterial circulation occluded, the twitch was observed to undergo an early potentiation (mean, 99 +/- 50%) followed by complete disappearance. A second, smaller phase of potentiation (mean, 25 +/- 30%) occurred during recovery and gave way to prolonged depression of the twitch. A comparison of these results with those obtained with an intact circulation suggested that the four phases in the behavior of the twitch were the net result of two processes, potentiation and fatigue, with different time courses. Provided they are timed appropriately, observations of twitch amplitude can provide useful information concerning the development of, and recovery from, muscle fatigue. PMID- 2920794 TI - Focal stimulation of human peripheral nerve with the magnetic coil: a comparison with electrical stimulation. AB - The hypothenar compound motor action potential (CMAP) response to ulnar nerve stimulation at the elbow was used as a test system in the human to compare excitations by a round magnetic coil (MC), 92 mm in outer diameter, and by electrical bipolar or tripolar stimulation. Optimal focality of excitation was obtained with the MC at 90 degrees to the extended arm and its plane parallel to the arm, i.e., an orthogonal-longitudinal orientation. Tangential orientation of the MC on the arm, i.e., laying it flat on the arm, powerfully excited additional structures. As expected from classical axonology, orthogonal-transverse orientations were the least effective. With orthogonal-longitudinal orientation and submaximal stimulation, the spread of excitation lateral to the median nerve at the wrist was of the order of 10-15 mm, the thickness of the MC being 12 mm. With the same orientation, the site of origin of the distally propagating impulse was estimated by comparing CMAP latencies to bipolar electrical (with cathode distal) and MC stimulation. Tripolar stimulation (with cathode intermediate) had no advantage over bipolar stimulation. The impulse originated 13-22 mm from the midpoint of the contacting edge. Rotating the MC through 180 degrees and thus reversing the field polarity did not significantly change the CMAP latency, indicating that the effective cathode and anode lay within a few mm of each other. Stimulating with a tilted MC resulted in a maximum CMAP when the orthogonal-longitudinal orientation failed to do so. A simple volume conductor model yielded a potential gradient of the right order of magnitude (35 mV/mm) when the MC stimulator output was 25% of maximum, i.e., a little above threshold for exciting ulnar motor axons. PMID- 2920795 TI - Undernutrition during early adult life significantly affects neuronal connectivity in rat visual cortex. AB - Male black and white Hooded Lister rats were undernourished for 29 days during early adult life. Undernourished rats had 30% more synapses per neurone in the visual cortex than matched controls. It is suggested that undernutrition may cause a delay in the normal decline of this ratio. PMID- 2920796 TI - Serotonin uptake in cerebral cortex cultures: imipramine-like inhibition by N isopropyl-p-iodoamphetamine. AB - In cultured rat neocortex, uptake of [3H]serotonin (5-HT) and the SPECT radiopharmaceutical N-isopropyl-p-[123I]iodoamphetamine (IMP) was demonstrated after 4 and 14 days in vitro. Both imipramine and cold IMP inhibited [3H]5-HT uptake. Uptake of [123I]IMP was inhibited by imipramine but not by cold 5-HT. The similarity in the behaviors of IMP and imipramine indicates that uptake of IMP might be related to a serotonergic uptake system in a way that is similar to that in which imipramine is related to such a system. PMID- 2920797 TI - Expansion of the bile acid pool changes the biliary transport characteristics of centrizonal hepatocytes. AB - We investigated whether acinar differences in taurocholate transport are responsible for the increased maximal secretory rate observed after expansion of the bile acid pool. The bile acid pool was expanded by cholate feeding for four days. Periportal and centrizonal hepatocytes were then probed by ante- and retrograde liver perfusion, respectively. In control animals, secretory rate constant (alpha 1) averaged 0.439 +/- 0.123 and 0.104 +/- 0.035 min-1 during ante and retrograde perfusion, respectively, in the absence of exogenous taurocholate. These values did not significantly change when taurocholate was infused. In cholate-fed animals, alpha 1 was comparable during antegrade perfusion but was significantly reduced (0.038 +/- 0.035, p less than 0.05) during retrograde perfusion in the absence of exogenous taurocholate, presumably owing to induction of cytosolic bile acid binding proteins. During loading with exogenous taurocholate, by contrast, alpha 1 was significantly accelerated (0.252 +/- 0.026; p less than 0.01) in centrizonal hepatocytes from bile-acid fed rats. Expansion of the bile acid pool is able to change the bile salt secretory characteristics of centrizonal hepatocytes toward those of periportal ones. PMID- 2920798 TI - A visual pigment of the sturgeon retina. AB - The visual pigments of hybrid sturgeon (a cross between Acipenser ruthenus (male) and Huso huso (female) have been studied both by the methods of incomplete partial bleaching and HPLC analysis. On the basis of the results obtained the relationship between the structure of opsins and the spectral characteristics of visual pigments is discussed. PMID- 2920799 TI - Studies on correlations between chloroquine-induced tissue damage and serum enzyme changes in the rat. AB - The administration of chloroquine to rats resulted in a significant elevation of serum enzymes and a corresponding decrease of these enzymes in the tissues. The changes in serum and kidney enzymes were most marked, thus indicating a primary renal dysfunction. PMID- 2920800 TI - Chronic cadmium intake results in dose-related excretion of metallothionein in urine. AB - Urinary excretion of metallothionein was measured by radioimmunoassay in rats given drinking water containing 5 or 50 mg cadmium/l for up to 2 years. The metallothionein levels corresponded to the concentration of cadmium in the drinking water and increased linearly over the course of the study. These results demonstrate that urinary metallothionein is a sensitive biological indicator of oral cadmium exposure. PMID- 2920801 TI - A basic protein from bovine brain that co-precipitates with tubulin in vitro. AB - A 193 kDa protein consisting of 58 kDa subunits, which has pI values of 8.50 and 8.65, was purified from bovine brain cytosol. It formed heavy precipitates with tubulin, and the molar ratio of tubulin dimer to this protein in the precipitate was 3.2. In contrast to microtubules containing ordinary microtubule-associated proteins, these complexes remained stable against cold and 1 mM CaCl2. PMID- 2920802 TI - Effect of thyroid hormone on somatomedin-C release from perfused rat liver. AB - The effect of thyroid hormone on plasma somatomedin-C (SmC) level and on SmC release from perfused rat liver was investigated. Plasma SmC levels and liver tissue SmC were significantly increased in thyroxine-treated rats. Physiological doses of triiodothyronine increased SmC release and SmC concentration in the perfused rat liver. These results indicate that thyroid hormone directly enhances the synthesis and release of SmC in the rat. PMID- 2920803 TI - The effect of homogenization temperature upon the apparent cellular compartmentalization of unoccupied estrogen receptor. AB - Homogenization of rat uterus at elevated temperatures results in an increased nuclear localization of unoccupied estrogen receptor. This is a nonlinear effect which is accounted for by an increased population of KCl-resistant nuclear binding sites at the elevated homogenization temperatures. PMID- 2920804 TI - Anti-bovine beta-lactoglobulin antibodies react with a human lactoferrin fragment and bovine beta-lactoglobulin present in human milk. AB - Human milk samples react against anti-bovine beta-lactoglobulin rabbit antibodies, as measured by a competitive radioimmunoassay. Immunoreactivity was positive even in milk from mothers consuming a diet free of cow's milk. An increase with a diet rich in cow's milk proteins was detected by immunoelectrophoresis. The human milk fraction cross-reacting with anti-bovine beta-lactoglobulin antibodies corresponds to the 20 kDa fragment from the N terminal end of human lactoferrin. Three regions of this fragment exhibit sequence homology with a sequence contained in cow's beta-lactoglobulin (between residues 124 and 141). PMID- 2920805 TI - Distribution of tunichrome and vanadium in sea squirt blood cells sorted by flow cytometry. AB - Specialized blood cells of many tunicates accumulate high concentrations of vanadium and phenolic peptide pigments called tunichromes (TC). In order to determine whether V and TC reside in the same cells, Ascidia nigra and Ascidia ceratodes blood cell subpopulations were isolated by fluorescence-activated cell sorting (flow cytometry) and chemically analyzed. V was found in the spherical, green/grey signet ring cells, and to a lesser degree in the mulberry-shaped, yellow/green morula cells (MRs), whereas free TC was detected mainly in MRs. PMID- 2920806 TI - Preliminary observations of a bacteriophage infecting Xenorhabdus luminescens (Enterobacteriaceae). AB - A bacteriophage infective to Xenorhabdus luminescens, a bacterial symbiont of heterorhabditid nematodes, was recovered from insects that supported poor nematode development. Plaque tests showed the phage particles to be infective only to primary and not secondary colonies of X. luminescens. The phage was not infective to X. nematophilus primaries or secondaries. The bacteriophage particles ranged 80-90 nm in length, with the head ranging from 40 to 50 nm in diameter. Restriction analysis was performed on isolated bacteriophage DNA. This first report of a bacteriophage from Xenorhabdus species has practical implications since it could be detrimental to cultures of Heterorhabditis nematodes that are being produced throughout the world for the biological control of insects. PMID- 2920807 TI - Glucosamine enhanced sperm-egg binding but inhibited sperm-egg fusion in mouse. AB - In order to study the sperm-egg recognition mechanism on the surface of the plasma membrane, zonae were removed from mouse eggs by exposure to acidic conditions. Sperm binding to denuded eggs was then observed in the presence of various sugars. Among several carbohydrates tested, only glucosamine (GlcN) was found to increase the number of sperm bound to eggs while inhibiting sperm-egg fusion. The inhibition was reversible; when denuded eggs were transferred to a GlcN free medium, a high rate of polyspermy was observed. PMID- 2920808 TI - Sex linkage of malic enzyme in Xenopus laevis. AB - Genetic analysis of mME variants (mitochondrial malic enzyme, E.C. 1.1.1.40) in Xenopus laevis revealed sex linkage of the mMe locus and indicated a WZ/ZZ type of sex determination. Codominant mMe alleles occur on both W and Z chromosomes, with a recombination frequency of 6.1% +/- 1.5% between mMe and the sex determining locus (or region). PMID- 2920809 TI - Isolation and structure of the strong cell growth and tubulin inhibitor combretastatin A-4. AB - The African tree Combretum caffrum (Combretacae) has been found to contain a powerful inhibitor of tubulin polymerization (IC50 2-3 microM), the growth of murine lymphocytic leukemia (L 1210 and P 388 with ED50 approximately 0.003 microM and human colon cancer cell lines [(e.g. LoVo (ED50 = 0.005 microgram/ml), HT 29 (ED50 0.02 microgram/ml, Colo 205 (ED50 = 0.07 microgram/ml), DLD-1 (ED50 = 0.005 microgram/ml) and HCT-15 (ED50 = 0.0009 microgram/ml] designated combretastatin A-4 (1c). The structure assigned by spectral techniques was confirmed by synthesis. PMID- 2920810 TI - Ventilatory and circulatory adjustments in the European eel (Anguilla anguilla L.) exposed to short term hypoxia. AB - Respiratory and circulatory (measured and calculated) variables were obtained at the same time in resting eels, during normoxia and after 1 h exposure to environmental hypoxia (water PO2 of 40 torr). In normoxia, values of respiratory and circulatory variables appeared less than those reported for most other fish. These differences could be partly explained by a lower level of standard metabolism and a greater uptake of O2 through the skin. Hypoxia caused a marked decrease in heart rate (40%), cardiac output (37%), ventral and dorsal arterial blood pressures (22% and 32%), associated with a constriction of prebranchial veno-venous shunt, and an increase in branchial vascular resistance (30%). Atropine treatment during hypoxia reduced, but did not abolish, bradycardia, and branchial vascular resistance remained unchanged. The lack of increase in cardiac stroke volume as well as the slowing of the heart in atropine-treated eel, could be regarded as metabolic effects of sustained hypoxia. The increase in branchial resistance and constriction of prebranchial veno-venous shunt could be regarded as a direct myogenic effect of hypoxia. Hypoxic exposure resulted in an increase in ventilatory water flow Vg (more than twofold), a decrease in gill O2 uptake (50%) and oxygen partial pressure in arterial (PaO2 80%) and mixed venous blood (PvO2 78%), and in increase in the transfer factor for O2 of the gills, TO2, (+66%). The ventilatory convection requirement increased (fivefold) while extraction (EwO2%) and effectiveness (Eff%) of gill oxygen transfer were maintained in spite of hyperventilation. Hypoxic hyperventilation reduced partial pressure of CO2 (PaCO2 from 3.4 to 0.7 torr) and markedly raised pH (pHa from 7.98 to 8.33) in arterial blood, thus causing a typical respiratory alkalosis, which resulted in increased O2 affinity and capacity of eel haemoglobin. PMID- 2920811 TI - Sideband transmission in interference filters and its implications for measurements of spectral sensitivity. AB - Commercial interference filters used in much of comparative vision science are constructed to suppress the transmission of light outside the primary passband. However, despite attempts to suppress sideband transmission, it does occur. This sideband transmission can lead to serious problems when working in the ultraviolet (UV) spectrum. The use of UV interference filters with a tungsten source which is calibrated with a silicon photodiode, produce large reproducible errors. PMID- 2920812 TI - Composition and distribution of retinal and 3-hydroxyretinal in the compound eye of the dragonfly. AB - Retinoids in the compound eyes of nymphs and adult dragonflies in 11 families of the 3 suborders were extracted by the oxime method, and analysed by high performance liquid chromatography. Almost all of the species examined contained both retinal and 3-hydroxyretinal in the compound eye. The ratio of 11-cis 3 hydroxyretinal to 11-cis retinal (3-OH ratio) was calculated as an index of the retinoid composition. The 3-OH ratios of the whole eye of nymphs in all the suborders and of adults of the suborder Zygoptera were very high, 2.2 at the minimum, but in Anisozygoptera and Anisoptera most of the ratios were distributed between 1 and 2.7. In the family Gomphidae, exceptionally low 3-OH ratios, less than 1, were observed in several species. The regional distributions of the retinals in the adult compound eyes were also examined. In the Zygopteran compound eye, both retinals were distributed evenly all over the eye, while in the compound eye of the other two suborders, the 3-OH ratios in the dorsal area of the eye were extremely low. In several species of Gomphidae and Libellulidae the ratios in the dorsal areas were zero. From the correspondence of these results and the compartment of the compound eye, it appeared that the large ommatidia in the dorsal area contained only retinal. This was confirmed when the large facet region in the dorsal part of the compound eye of an Anax was excised and examined, and only retinal was detected. However, the ventral area of the true dragonflies' compound eye which did not include the large ommatidia contained both retinals, and the 3-OH ratio was more than ten. The biological significance of using both retinals as chromophores of visual pigments in the dragonfly eye is discussed in relation to the structure of the ommatidia and to the vision of dragonflies. PMID- 2920813 TI - Gastric evacuation of the lemon shark Negaprion brevirostris (Poey) under controlled conditions. AB - Gastric evacuation of the juvenile lemon shark, Negaprion brevirostris, a tropical inshore apex predator, was studied in the laboratory under conditions of 25 degrees C and 32% salinity. Sharks were starved for 48-96 h after which they were fed a 2.7% body weight meal of fish fillet. Gastric evacuation was assessed by stomach lavage every 3 h for 24 h thereafter. Results showed that the gut is emptied in about 24 h with fillets being removed from the stomach following the equation Y = Yoe-bt, where Y is percent of meal recovered at time t, Yo is the initial meal size, and b is the instantaneous rate of evacuation. The exponential function of gastric evacuation in the lemon shark is similar to that in teleosts, but the kinetics are slower. The caloric density of the meal remaining in the stomach increased, approaching that of protein in the first 12 h after feeding, as carbohydrates (glycogen) were digested. After 12 h the caloric value dropped as protein was digested, suggesting an orderly and efficient intake of food energy by the lemon shark. PMID- 2920814 TI - The effects of forced and voluntary diving on plasma catecholamines and erythrocyte pH in the aquatic anuran, Xenopus laevis. AB - The lactacidosis and hypoxaemia associated with enforced diving in Xenopus leads to a marked increase in circulating catecholamines, a phenomenon not observed during periods of voluntary diving. The magnitude of the catecholamine surge (predominantly noradrenaline) during an enforced dive appears to be matched to the severity of the hypoxaemia and/or acid-base disturbance. Indeed, a strong linear correlation was found between the decrease in arterial pH and the rise in plasma catecholamines that resulted from an enforced 60 min dive. During that time, the levels of plasma adrenaline and noradrenaline showed a strong inverse exponential correlation with arterial oxygen tensions (PaO2). Simultaneous measurements of red cell pH showed that Xenopus does not regulate its erythrocyte pH in the face of a plasma acidosis, unlike the adrenergically mediated pH regulation of red cells of certain teleost fish. PMID- 2920815 TI - O2 tension, swimming-velocity, and thermal effects on the metabolic rate of the Pacific albacore Thunnus alalunga. AB - The oxygen consumption rates (VO2) of 9 albacore tuna, Thunnus alalunga (8.5-12 kg) were measured at sea in a swimming respirometer to determine the effects of relative swimming velocity, ambient O2 tension, and water temperature. Significant positive relationships were obtained between tail-beat frequency and relative speed and between relative speed and VO2. The albacore metabolic rate was not appreciably affected by exposure to water temperatures ranging from 13.5 degrees to 16.9 degrees C. Brief exposure to hyperoxia (200-400 mmHg), which was done to reduce the initial stress upon fish in the respirometer, did not affect VO2. Hypoxia (50-99 mmHg), however, did tend to reduce VO2 and affect swimming velocity. PMID- 2920816 TI - Comparative morphology of the eyes of Sagitta (Chaetognatha) in relation to depth of habitat. AB - A survey of the eye structure in 10 species of Sagitta (phylum Chaetognatha) which differ in habitat was carried out: 5 epipelagic, 4 mesopelagic and 1 bathypelagic species. Paying attention to the dimension of the pigment cell, and assuming that the perforated lamellae are the photoreceptive regions (PRs), we classified the eyes of the 10 species into 5 types. In type I and II eyes there is one large pigment cell. The maximum length of the pigment cell relative to that of the eye (PC/E) is more than 30% in dorsal view and more than 50% in transverse sections. The pigment cell is surrounded by a wide area of the PR that we designated "central PR". The type II eye possesses, in addition, near the periphery of the eye, masses of PRs which measure about 15% of the central one in size. We call these positionally separated PRs "peripheral PR". In type III eyes the pigment cell and the central PR are small (PC/E is about 10% in dorsal view and less than 40% in transverse sections) and the peripheral PRs are scattered. In type IV eye the pigment cell is also small and the central PRs extend to the periphery. In type V eye the pigment cell is absent and the PR occupies a wide area of the dorsal half of the eye. The type I and II eyes were found mostly in epipelagic species, the type III and IV, in mesopelagic species, and the type V, in bathypelagic species. The adaptational significance of the small pigment cells, the peripheral PRs, and the pigmentless eye is discussed. In addition, we report a new type of photoreceptive cell in mesopelagic Sagitta zetesios, in which two receptoral processes emerge from single cells, in contrast to one in all the other species of Sagitta. PMID- 2920817 TI - Hepatic structural correlates of liver fibrosis: a morphometric analysis. AB - Liver fibrosis is an important feature of many liver diseases, and the assessment of fibrosis is essential for diagnosis and prognosis. Liver needle biopsy, however, tends to sample preferentially the soft parenchyma, which poorly reflects the true extent of fibrosis. Therefore, we have searched for capsule and parenchymal features that are correlated with the fibrosis. To test for these correlations, we used a morphometric analysis of a rat model of liver fibrosis. We demonstrated that, of the variables examined, capsule thickness was the best correlate of liver fibrosis. Our results also showed that there were parenchymal structures that underwent changes that were well-correlated with the development of fibrosis in the liver. These changes were identified as increases in hepatocyte nucleus, cytoplasm, and mitochondria. These facts suggest that, at least in a rat model of fibrosis, capsule thickness is a useful parameter by which to assess liver fibrosis and that specific and apparently adaptive parenchymal changes are well-correlated to fibrosis. PMID- 2920818 TI - Cellular mechanisms of toxicity and tolerance in the copper-loaded rat. II. Pathogenesis of copper toxicity in the liver. AB - The distribution of copper has been studied in the liver of the copper-loaded rat at the ultrastructural level by X-ray electron probe microanalysis in order to clarify the pathogenesis of copper-induced damage. Male rats fed a high copper diet (1500 ppm) for 16 weeks were killed at intervals; their livers were removed and fixed in 4% paraformaldehyde and 2% glutaraldehyde for electron microscopy and were analyzed for copper by AA spectrophotometry. Three different forms of lysosomes were identified with respect to their morphology and X-ray emission profiles: Type I lysosomes appeared early and contained iron and zinc in addition to markedly elevated copper peaks, whereas later appearing Type II lysosomes included sulfur and phosphorus in addition to copper. Type III lysosomes were associated with the recovery period and contained much reduced elemental residue. Degenerative changes were not observed in any of the three types of lysosomes. Copper and other elemental residues, including sulfur, were also identified within the hepatic parenchymal cell nuclei and by contrast were associated with irreversible nuclear damage. Nuclear copper is directly injurious to this organelle and responsible for the subsequent cell death whereas copper contained within lysosomes is apparently innocuous. PMID- 2920819 TI - Overall proteolysis in perfused and subfractionated chemically induced malignant hepatoma of rat: effects of amino acids. AB - Control livers and chemically induced hepatoma-bearing livers of nonstarved rats were perfused cyclically with and without the addition of amino acids (known to suppress proteolysis) to the perfusate. Morphologic analysis of the fractional cytoplasmic volume of the lysosomal apparatus (dense bodies and autophagic vacuoles) demonstrated that the addition of amino acids to the perfusion medium inhibited autophagic sequestration of cytoplasm in both tumor and control hepatocytes, although the inhibition was stronger in control than in tumor hepatocytes. The fractional cytoplasmic volume of autophagic vacuoles (AVs) was larger in hepatoma cells than in control hepatocytes regardless of whether amino acids were added or not. The transition (degradation of sequestered cytoplasm) of AVs into dense bodies seems to be prolonged in malignant hepatoma cells. Assessment of rates of protein degradation both in the perfusion medium and in isolated lysosomes disclosed that proteolysis was much lower in tumor liver than in control liver. This can be explained by lower lysosomal enzyme activities in tumor cells, as was evident from tissue homogenate and isolated lysosomes. The addition of amino acids to the perfusate reduced total proteolysis from 1.73 to 0.78% per hour in control hepatocytes and from 0.49 to 0.33% per hour in tumor hepatocytes, i.e., inhibitions of 55 and 33%, respectively. Proteolysis as estimated from isolated lysosomes was also inhibited by amino acids added to the perfusion medium but the inhibition was more conspicuous in control (from 14 to 7.4%) than in tumor cells (from 5.2 to 3.6%). In conclusion, the results show that the relative cytoplasmic volume of AVs is higher but overall proteolysis lower in malignant hepatoma tissue than in control liver. Amino acids in perfusion medium inhibit overall proteolysis and AVs sequestration in both tumor and control hepatocytes, although the inhibition is stronger in control hepatocytes. Thus, even highly neoplastic cells maintain their ability to respond to physiologic regulators. PMID- 2920820 TI - Cytoskeletal changes induced in vitro by 2,5-hexanedione: an immunocytochemical study. AB - The effects of 2,5-hexanedione, the main metabolite of the solvents hexane and methyl butyl ketone, have been explored in different in vitro epithelial (CG5 and HEp-2) and melanoma (JR8) cells by means of immunochemistry and electron microscopy. The administration of the toxicant to the cell monolayers at noncytolytic concentrations for 24 and 48 hr exerted several effects on the cell lines studied. Most epithelial and melanoma cells detached from the substrate were in the mitotic phase, whereas cells adhering to the substrate showed time dependent organelle changes. In fact, after treatment with 2,5-hexanedione, mitochondria appeared swollen, with distorted cristae and rarefied matrix; changes in intracytoplasmic vesicles were also detected. Cytoskeletal components were also investigated. A remarkable rearrangement of microfilaments and intermediate filaments (keratin and vimentin) was detected in a time-dependent manner. In particular, actin ruffles and intermediate filament aggregates were observed. Furthermore, the microtubular apparatus seemed to be less affected. The results here reported seem to indicate cytoskeletal components as probable targets of 2,5-hexanedione cytotoxicity in cultured cells. PMID- 2920821 TI - Membrane damage in leukemic cells induced by ether and ester lipids: an electron microscopic study. AB - This paper reports a scanning electron microscopy (SEM) study of different leukemic cell lines exposed to 1-octadecyl-2-methyl-rac-glycero-3-phosphocholine (ET-18-OMe). This is an ether lipid analog of platelet activating factor (1-alkyl 2-acetyl-sn-glycero-3-phosphocholine) which inhibits neoplastic cell growth in vitro and in vivo and is believed to exert its action through an interaction with the plasma membrane. In this paper evidence of the morphological alteration of leukemic cell membranes due to the exposure to varying concentrations of ET-18 OMe in vitro and in vivo is presented. This membrane damage consists of formation of blebs and holes, and the severity of these two phenomena correlate with the degree of cell viability loss. These alterations were analyzed in comparison to those induced by the known and structurally related permeabilizing agent, lysophosphatidylcholine, an ester lipid. PMID- 2920822 TI - Dependence of the length of the heavy chain of chymotryptic subfragment 1 on the temperature of myosin digestion. AB - Limited digestion of filamentous myosin with chymotrypsin at 0 degrees C in the absence of divalent cations generates two forms of subfragment 1 (S1), with heavy chains of 95 kDa and 98 kDa. The difference is at the C-terminal end of the chain. The 98 kDa form prevails, in contrast to the preparations obtained by digestion at room temperature which consist of the shorter species and only traces of the longer one. The results support the idea of a temperature-dependent conformational transition at the head-rod junctional region of the myosin heavy chain. PMID- 2920824 TI - Characterization of platelet-activating factor-induced elevation of cytosolic free calcium concentration in eosinophils. AB - In order to evaluate the role of calcium in the activation processes in eosinophils induced by platelet-activating factor (PAF), we investigated the changes in free cytoplasmatic Ca2+ concentration using fura-2. PAF causes a rapid and transitory rise of the intracellular free calcium ion concentration [( Ca2+]i) in purified guinea pig eosinophils of approx. 1000 nM above a basal level of 120.7 +/- 36.5 nM (n = 10). The effect was dose-related with a maximum rise at 1000 nM PAF and an EC50 of 17.4 nM and specifically inhibited by the PAF antagonist WEB 2086 with an IC50 of 95.5 nM. WEB 2086 did not affect either the leukotriene B4- or the fMet-Leu-Phe-induced elevation of [Ca2+]i. The response to PAF was dependent on external Ca2+ as it was significantly inhibited by EGTA (85.6 +/- 5.4%) and Ni2+ (95.8 +/- 2.1%) but not by the dihydropyridine antagonist nimodipine. We conclude that Ca2+ entry via receptor-operated Ca2+ channels may be involved in PAF-induced degranulation of eosinophils. PMID- 2920823 TI - Carnitine cycle in brown adipose tissue mitochondria as a tool for studying the regulatory role of fatty acids in the uncoupling protein function. AB - A concerted function of purine nucleotide (PN) binding and fatty acid (FA) release from the uncoupling protein (UP) resulting in the maximum coupling (potential) of brown adipose tissue (BAT) mitochondria was demonstrated. The uncoupling effect of FA was studied (at 4 mM MgCl2): 17 nmol oleate per mg protein caused a slight uncoupling with 8.9 mM ATP but with ATP below 3.6 mM almost total uncoupling was achieved. This shows that the PN-controlled gate can be stabilized in the closed conformation (with 8.9 mM ATP), also when FA is bound to UP. The sensitivity of the FA effect to ATP proves that oleate directly interacts with UP. The closed conformation of the H+ channel of UP is then abolished by oleate when a lower free ATP concentration is maintained outside. PMID- 2920825 TI - Molecular structure of the human alcohol dehydrogenase 1 gene. AB - The structure and nucleotide sequence of an allele at the ADH1 locus have been determined. The nucleotide sequence of this allele is identical to that of a cDNA clone [(1986) Biochemistry 25, 2465-2470] and the intron positions of the ADH1 gene are identical to that of the ADH2 gene [(1986) J. Biol. Chem. 261, 2027 2033]. PMID- 2920826 TI - Nitrile hydratase of Rhodococcus sp. N-774. Purification and amino acid sequences. AB - The nitrile hydratase of Rhodococcus sp. N-774 was purified and crystallized. The enzyme is composed of two different subunits (molecular masses: subunit alpha, 28,500 Da; subunit beta, 29,000 Da). The amino-terminal amino acid sequence of each subunit was determined. There is no sequence homology between the two subunits, suggesting that the peptides originate from different cistrons. The activity of the purified enzyme did not decrease during incubation in the dark, whereas it gradually decreased in intact cells. PMID- 2920828 TI - Evidence for the monomeric nature of thymosins. AB - According to gel-filtration experiments, alpha- and beta-thymosins appear to form oligomers, which are 4-5-fold larger than the corresponding polypeptides. However, on analysis by sedimentation equilibrium ultracentrifugation, prothymosin alpha and thymosin beta 4 showed relative molecular masses of 12,800 and 4600, which are close to the values calculated from their amino acid sequences, confirming their existence in solution as discrete monomeric entities. PMID- 2920827 TI - Myristic acid is the NH2-terminal blocking group of the 43-kDa protein of Torpedo nicotinic post-synaptic membranes. AB - The NH2-terminal blocking group of the 43-kDa peripheral membrane protein (43-kDa protein) of Torpedo post-synaptic membranes has been identified as myristic acid. To identify that blocking group pure 43-kDa protein was digested with trypsin and the blocked tryptic peptide was isolated by reverse phase HPLC. That peptide coeluted with and had the same amino acid composition as a synthetic peptide, myristoyl-Gly-Gln-Asp-Gln-Thr-Lys, the structure of the amino terminus predicted from the protein sequence deduced from a cDNA clone. The presence of myristate was confirmed by the precise molecular mass of the peptide, 886.5266, determined by fast atom bombardment mass spectroscopy. PMID- 2920829 TI - Electron microscopy study of non-precipitating anti-dinitrophenyl antibodies. AB - Non-precipitating anti-dinitrophenyl pig immunoglobulins G have been studied by negative staining, freeze-drying and high-resolution shadow casting. The general morphology of the molecules is described. The predominant conformation of antibody molecules is a tripod-like one. PMID- 2920830 TI - Convenient plasmid vectors for construction of chimeric mouse/human antibodies. AB - Chimeric antibodies composed of mouse-derived variable regions and human-derived constant regions have been developed for clinical use. However, construction of chimeric mouse/human genes in expression vectors is time-consuming work. In this study, we developed convenient vectors for construction of chimeric mouse/human antibodies. The protocols are as follows: In mouse hybridomas and B cells, most active VH and V kappa genes can be identified as rearranged bands by Southern hybridization of EcoRI- and HindIII-digested DNAs with JH and J kappa probes, respectively, and such fragments can be isolated in lambda-EcoRI and lambda HindIII vectors, respectively. We constructed two plasmids: pSV2-HG 1 gpt contains human C gamma 1 and Ecogpt genes, and only one EcoRI site upstream of the C gamma 1 gene; pSV2-HC kappa neo contains human C kappa and neo genes, and only one HindIII site upstream of the C kappa gene. An isolated EcoRI fragment containing a VHDHJH gene and a HindIII fragment containing a V kappa J kappa gene are inserted into pSV2-HC kappa neo, respectively. Both resulting plasmid DNAs are co-transfected into SP2/0 cell, a non-Ig-secreting mouse myeloma. Transformants are selected by both mycophenolic acid and G418. With this procedure, it takes only 2 months to obtain chimeric antibodies. PMID- 2920831 TI - Interaction of iodoacetamidofluorescein-labelled tropomyosin with deoxyribonuclease I. AB - 5-Iodoacetamidofluorescein (IAF) reacted with rabbit cardiac muscle tropomyosin (TM) to yield a highly fluorescent product, IAF-TM. The extent of labelling reached one fluorescein group per TM molecule in solutions at pH 8.5. While fluorescence polarization values for IAF-TM solutions were unaffected by the presence or absence of KCl, addition of pancreatic deoxyribonuclease I (DNase I) resulted in a 10% drop, suggestive of a greater freedom of motion of the fluorescein label in the presence of DNase I. Furthermore, a 15% increase in slopes of Stern-Volmer plots for IAF-TM in the presence of DNase I demonstrated a greater susceptibility of the fluorescein group to dynamic quenching by iodide. These results suggest that interaction between DNase I and TM produces a localized unfolding of the coiled coil near the IAF reactive site on TM. PMID- 2920832 TI - GTP interacts through its ribose and phosphate moieties with different subunits of the eukaryotic initiation factor eIF-2. AB - We have previously shown that a GTP derivative bearing p-azidoaniline at the gamma-phosphate group specifically labels the gamma-subunit of eukaryotic initiation factor eIF-2. In the present study a new GTP derivative carrying the photoreactive group at the ribose moiety of GTP was applied for affinity labeling of eIF-2 in different initiation complexes. Using this GTP analogue the beta subunit of eIF-2 was found to be specifically labeled in all complexes investigated. It is concluded that GTP interacts with both the beta- and gamma subunit of eIF-2: the guanosine moiety is in contact with the beta-subunit and the gamma-phosphate group with the gamma-subunit. PMID- 2920833 TI - Inhibition of myeloid differentiation by inhibitors of ADP-ribosylation. AB - Inhibitors of ADP-ribosylation inhibited the myeloid differentiation of murine myelomonocytic leukemia, WEHI-3BD+ cells induced by granulocyte colony stimulating factor. Benzamide, at 2.0 mM, inhibited 50% of the WEHI-3BD+ cell differentiation but had no significant effect on the proliferation. However, benzylaminododecylguanine hydrochloride and p-methoxylbenzylaminodecamethylene guanidine sulfate at 2.0 and 2.2 microM, respectively, inhibited 50% of proliferation but had no effect at all on differentiation. The differential effects of inhibitors provide a model to study the role of ADP-ribosylation in myeloid differentiation. PMID- 2920834 TI - Squalene epoxide cyclase and microemulsion. AB - Squalene epoxide cyclase was extracted from microsomal preparations of rat liver using anionic, cationic and non-ionic microemulsions. The anionic microemulsion was the best with respect to protein solubilisation, extracted cyclase activity and stability of this activity over time. The activity assay showed cyclase activity to be higher in anionic microemulsion than in buffer in the presence of surfactant. Calcium chloride in the anionic microemulsion had a stabilising effect and less total protein seemed to be extracted. PMID- 2920835 TI - Isolation and sequencing of a cDNA clone encoding 107 kDa sialoglycoprotein in rat liver lysosomal membranes. AB - A cDNA for 107 kDa sialoglycoprotein (LGP 107), the major protein component of rat liver lysosomal membranes, was isolated and sequenced. The 1.8 kbp cDNA contained an open reading frame encoding a polypeptide consisting of 386 amino acid residues (Mr 41,914). The deduced NH2-terminal 10-residue sequence is identical with that determined for purified LGP 107. The primary structure deduced for LGP 107 contains 20 potential N-glycosylation sites and exhibits 82.5, 43 and 60% sequence similarities to mouse LAMP-1, chicken LEP 100, and a 120-kDa human lysosomal glycoprotein, respectively. Among these lysosomal glycoproteins, the amino acid sequence of the putative transmembrane segment is highly conserved. Northern blot hybridization analysis identified a single species of LGP 107 mRNA (2.1 kbp in length) in rat liver, kidney, brain, lung, spleen, heart and pancreas, although its level in pancreas was very low. PMID- 2920836 TI - Human platelets release alpha-6-L-fucosyltransferase upon activation. AB - Previously we have shown that human platelets release alpha-6-L fucosyltransferase (EC 2.4.1.68) during coagulation of blood [(1987) Glycoconjugate J. 4, 43-49]. Here we report that agonists which induce platelet aggregation bring about release of the enzyme. In quantitative terms the release of alpha-6-L-fucosyltransferase by washed, aggregated platelets was very similar to that occurring during blood coagulation. PMID- 2920837 TI - Leupeptin does not affect the normal signal transduction mechanism in platelets. AB - Calpains are Ca2+-dependent serine proteases that can regulate protein kinase C mediated cellular events by cleaving the membrane-bound native enzyme to yield an activated cytosolic fragment. Inhibition of calpain by leupeptin may cause enhancement or inhibition of cellular functions depending on the nature of the protein kinase C reaction involved. We have studied the effects of leupeptin on platelet responses (aggregation, secretion, thromboxane B2 formation and intracellular Ca2+ and pH changes) induced by either thrombin, collagen or phorbol 12-myristate 13-acetate (TPA), which are known to activate protein kinase C by different mechanisms. Only thrombin-induced responses were inhibited by leupeptin. This suggests that the inhibitory effect of leupeptin is not due to antagonism of calpain in this system, but to direct interference with the proteolytic effect of thrombin. PMID- 2920838 TI - Activation by calcium of AMP deaminase from the human red cell. AB - We have investigated the effects of Ca2+ on AMP deaminase from human red cells. At variance with the other known modulators, Ca2+ increased the apparent affinity for AMP without modifying the characteristic positive cooperativity of the enzyme towards the substrate. Ca2+ sensitivity was not modified by dialysis, but dilution of the haemolysate produced an activation of the enzyme similar to that induced by Ca2+. Simultaneously, the Ca2+ dependence was lost. The sensitivity to other modulators, such as ATP, diphosphoglycerate or phosphate, was not modified by dilution. Partial purification of the enzyme produced the same effects as haemolysate dilution. These results may be interpreted to mean that Ca2+ acts by antagonizing an endogenous inhibitor present in red cell lysates. PMID- 2920839 TI - The crystal structure of the three-iron ferredoxin II from Desulfovibrio gigas. AB - The crystal structure of oxidized ferredoxin II from the sulfate-reducing bacterium Desulfovibrio gigas has been determined and refined at 1.7 A resolution. The folding of the polypeptide chain is similar to that of the 2[4Fe 4S] ferredoxin in Peptococcus aerogenes, except for an extended helical segment near the C-terminus. The single [3Fe-4S] cluster in D. gigas is similar to a [4Fe 4S] cluster, but lacks one Fe atom and is coordinated to Cys-8, -14 and -50. The side chain of Cys-11 is not bound to the cluster, but is rotated toward the solvent and modified by some, as yet undetermined, chemical group. Cys-18 and Cys 42 form a disulfide bridge. A previously undetected extra amino acid is found after residue 55. PMID- 2920840 TI - Degradation of type IX collagen by matrix metalloproteinase 3 (stromelysin) from human rheumatoid synovial cells. AB - The degradation of type IX collagen, a minor collagen in cartilage, was examined by treatment with three different types of matrix metalloproteinases (MMPs) purified from the culture medium of rheumatoid synovial cells. Neither MMP-1 (collagenase) nor MMP-2 (so-called 'gelatinase') could digest type IX collagen, but MMP-3 (stromelysin) readily degraded it into smaller fragments. This suggests that MMP-3 may be responsible for the pathological degradation and/or normal turnover of type IX collagen. PMID- 2920841 TI - A peptidyl alpha-amidation activity in chromaffin granules of bovine adrenal medulla. AB - Peptidyl alpha-amidation activity in bovine adrenal medulla has been localized in chromaffin granules by density gradient centrifugation. The activity was found to be both soluble and membrane-associated. Both enzymatic activities were stimulated by the addition of Cu2+ and ascorbate. The pH maximum for alpha amidation in the chromaffin granules in pH 8.0-8.5. By gel filtration, the soluble enzyme activity appeared as a protein of approx. 40 kDa. It is suggested that this enzyme is involved in the carboxyl-terminal amidation of metorphamide, amidorphin and neuropeptide Y. PMID- 2920842 TI - Safety guidelines for the andrology laboratory. PMID- 2920843 TI - Interobserver variation in estimation of day of conception intercourse using selected natural family planning charts. AB - In order to study outcome of pregnancy related to timing of conception it is necessary to have both markers of ovulation and records of intercourse. Natural family planning (NFP) charts where the woman records basal body temperature (BBT) and mucus signs are ideal for this purpose. Much work has been done relating timing of BBT and mucus signs to ovulation, but very little work has been done to examine interobserver agreement on the interpretation of these signs. Four NFP experts examined 28 NFP pregnancy charts to determine the BBT rise, the mucus peak, and two most likely days of conception intercourse. The charts were selected because they provided difficulties in interpretation. The reviewers were able to agree on the most probable day of conception intercourse in 96.4% of cases, on the mucus peak in 74.1% of cases, and on the interval between the most probable conception intercourse and mucus peak in 70.4% of cases. There was poor agreement on the first day of the BBT rise (38.5%). The authors conclude that in selected difficult NFP charts, the mucus peak is a more valid indirect measure of ovulation both because it is subject to less interobserver variation and because it more closely approximates the timing of ovulation. PMID- 2920844 TI - Male or female sterilization: a comparative study. AB - The study compares 709 males and 546 females recruited from a well-defined geographic area and sterilized during a 5-year period at the same hospital. Medical records were reviewed and questionnaires sent out. Widespread satisfaction with the sterilization was found. The sterilized women had experienced contraceptive side effects and failures more often than the men. Only 70% of the laparoscopic sterilizations could be carried out during a 1-day admission, 25% of the women complained about long-term sequelae, and there were 1% failures. The vasectomies were carried out on an outpatient basis, there were few postoperative symptoms, and 0.5% failures were recorded. Female sterilization was at least four times as expensive as vasectomy. It is concluded that vasectomy is generally to be preferred to female sterilization, and that the preoperative guidance should involve both man and wife. PMID- 2920845 TI - Human embryo viability after freezing with dimethylsulfoxide as a cryoprotectant. AB - This study concerns the effects of a slow freezing and thawing protocol using dimethylsulfoxide (DMSO) as a cryoprotectant on the survival and viability of 319 supernumerary human embryos produced after in vitro fertilization. One hundred twenty-one transfers were performed in a natural cycle and 18 pregnancies were achieved (15%), from which 14 were ongoing (12%). Overall, 52% of the thawed embryos retained at least 50% of their initial blastomeres intact after thawing, and were replaced. Survival was strongly correlated to prefreezing embryonic quality, as 78% of type I embryos, 55% of type II, 40% of type III, and none of type IV could be transferred. Implantations were obtained from type I embryos (21% per embryo replaced) and from type II (14.5%), whereas none of the type III embryos resulted in a pregnancy. In the authors' experience, using the DMSO protocol, the best pregnancy rates were achieved when replacing 8-cell embryos of high morphologic prefreezing quality. No statistically significant difference could be demonstrated, however, in implantation rates between 8-cell and 4-cell embryos, or between synchronously and asynchronously dividing concepti. PMID- 2920846 TI - The impact of spermatic vein ligation on the male factor in in vitro fertilization-embryo transfer and its relation to testosterone levels before and after operation. AB - Criteria for improved semen quality after varicocele operations are not clear, as they do not express sperm fertilization capacity, its most important qualification. Twenty-two couples, 12 with mechanical female infertility (group I) and 10 with normal female fertility (group II), in whom the husband had subfertile semen in the presence of varicocele, and who had failed preoperative in vitro fertilization-embryo transfer (IVF-ET) attempts, were readmitted for the IVF-ET procedure following the repair of varicocele. In group I, a 20% pregnancy rate was achieved after the operation, while no pregnancies occurred before surgery. In group II, four pregnancies (40%) were achieved after operation. Plasma testosterone (T) levels demonstrated a significant increase in 50% of the patients in both groups after surgery, resulting in a concurrent improved fertilization, cleavage, and pregnancy rates. PMID- 2920847 TI - Interrelationships among semen characteristics, antisperm antibodies, and cervical mucus penetration assays in infertile human couples. AB - Semen characteristics, antisperm antibodies, and cervical mucus penetration studies were analyzed in 754 couples and 95 men undergoing infertility evaluation. The means for the different semen/sperm variables were within ranges published for fertile men. Ages of the men ranged from 22 to 55 years and accounted for a small amount of variation. Sperm counts were lowest in September, December, and January, and highest in April, May, October, and November. Of the sperm characteristics, morphology appeared to be associated with the most other variables. Specimens with more than 50% abnormal sperm forms were overall of significantly poorer quality in terms of sperm counts, motility, forward progression, and ability to penetrate cervical mucus. Antisperm antibodies (agglutinating and immobilizing) were detected in the serum samples of 19.0% of the men, 20.4% of the women, and 32.8% of the couples where one or both partners were positive. Agglutinating antibody titers were significantly correlated between partners. Serum titers of antisperm antibodies were associated with decreased sperm counts, motility, forward progression, and normal forms (immobilizing antibodies). Multiple correlation analysis indicated significant independent effects of sperm concentration, motility, forward progression, and antibodies on sperm-cervical mucus penetration scores of the men. In women, cervical mucus penetration was adversely affected by the presence in the serum of sperm agglutinating antibodies and of immobilizing activity in the cervical mucus. PMID- 2920848 TI - Absorption of dihydrotestosterone (DHT) after its intramuscular administration. AB - In order to produce a sustained release system for natural androgens, two groups of six hypogonadal males received intramuscular (IM) 40 mg crystalline dihydrotestosterone (DHT), either with particle size of less than 50 microns (DHT M) or between 100 and 150 microns (DHT-C). Serum DHT was analyzed through 51 days of follow-up. In the DHT-M group, serum DHT was above pretreatment values for 17 days, whereas in the DHT-C group, this period was extended over 50 days. The area under the serum concentration-time curve and the half-life of absorption calculated for the DHT-C group were greater than those obtained for the DHT-M group (55.1 ng/day/ml and 21 days vs. 14.5 ng/day/ml and 6 days; P less than 0.01). The authors conclude that DHT injection appears to be an effective and convenient technique for restoring serum physiologic DHT levels. This approach is suitable for long-term substitution therapy. PMID- 2920849 TI - Seminal prolactin and its relationship to sperm motility in men. AB - Semen assessment and levels of serum and seminal plasma prolactin (PRL) were determined in 81 men. In subjects with both normal sperm concentrations and normal sperm motility, the levels of serum and seminal plasma PRL were 14.7 +/- 1.48 and 10.0 +/- 1.05 ng/ml (mean +/- standard error of the mean, SEM, P less than 0.05), respectively. This difference is not observed either in subjects with polyzoospermia with normal sperm motility, or in those with oligozoospermia. Serum PRL was higher in azoospermia and also in subjects with lower levels of seminal citric acid. Seminal plasma PRL was directly related to sperm motility (r = 0.70, P less than 0.01) and inversely related to sperm concentration (r = -0.42 P less than 0.05). Seminal PRL was increased in subjects with higher levels of seminal citric acid and decreased in subjects with lower levels of corrected seminal fructose. Serum and seminal plasma PRL did not change significantly in subjects with different concentrations of serum testosterone. PMID- 2920850 TI - Successful single-cell biopsy and cryopreservation of preimplantation mouse embryos. AB - We have previously observed that preimplantation embryo biopsy in the mouse causes a reduction in implantation rate in utero. After minor modifications to the technique, we now find that sampling a single blastomere from the 4-cell mouse embryo does not compromise continued development in vitro or in vivo. When transferred to pseudopregnant foster mice, 60.3% and 64.3% of biopsied and control embryos, respectively, implanted into the uterine wall, and 52.6% and 52.4% of biopsied and control embryos, respectively, developed into fetuses. In a separate series of experiments, we have demonstrated that biopsied mouse embryos can be successfully cryopreserved by ultrarapid freezing even though they have a punctured zona pellucida. Biopsied (frozen-thawed), control (frozen-thawed), and nonfrozen embryos had an implantation rate of 81.1%, 74.3%, and 74.1%, respectively, and a fetal formation rate of 62.2%, 62.9%, and 66.7%, respectively. PMID- 2920851 TI - Unilateral gamete intrafallopian transfer: the preferred method? AB - Pregnancy occurred in 8 of 14 patients with the unilateral transfer of three or four oocytes at GIFT procedures. These results suggest that unilateral GIFT may be at least as successful as the bilateral approach. It would appear that unilateral GIFT rather than in vitro fertilization should be used for patients with one normal fallopian tube, and if the pregnancy rates with unilateral GIFT are substantiated, then this would be preferable to the bilateral approach, as operating time is shorter and there is less risk of trauma to the fallopian tubes at the time of gamete transfer. PMID- 2920852 TI - Triplet pregnancy following oocyte donation to a functionally agonadal woman. AB - Reported is the first triplet gestation following oocyte donation to an agonadal woman. The transfer of five ova resulted in implantation of all five, with continued embryonic development in three. Pregnancy support was provided by exogenously administered oral E2 and intramuscular P for 100 days, at which time placental hormone production solely maintained the gestations. PMID- 2920853 TI - Experience relating to pregnancy, lactation, and the after-weaning condition of hyperprolactinemic patients treated with bromocriptine. PMID- 2920854 TI - Free testosterone levels during the menstrual cycle in obese versus normal women. AB - In a group of seven normally ovulating moderately obese women, testosterone parameters were studied throughout the menstrual cycle and compared with values obtained in normal-weight control women. Plasma T, percent free T (unbound), and free T concentrations were higher and exhibited little variation during the phases of the cycle compared with the normal-weight controls. Testosterone production and its parameters thus are higher in even moderately obese women. PMID- 2920856 TI - Salpingitis isthmica nodosa: evidence it is a progressive disease. PMID- 2920855 TI - Cortisol levels in human follicular fluid. AB - This study shows that cortisol levels in follicular fluids in stimulated cycles were correlated with oocyte maturity and in vitro fertilizability. The levels were significantly higher than the concentrations found in spontaneous cycles. Our findings suggest that the presence of cortisol in follicular fluid may play a role in follicular development and oocyte maturation. PMID- 2920857 TI - Evaluation of vasovasostomy candidates by deoxyribonucleic acid flow cytometry of testicular aspirates. AB - Flow cytometry can be performed on testicular aspirates of vasovasostomy candidates preoperatively. On the basis of ploidy ratios and debris components, DNA histograms can be classified as normal or abnormal. Using this method, the likelihood of the presence of sperm may be predicted. PMID- 2920858 TI - Luteal hCG in ovulation induction. PMID- 2920859 TI - Classification of mullerian anomalies. PMID- 2920860 TI - [HLA-A, B, C phenotype frequencies in progressive systemic scleroderma]. AB - In 41 patients suffering from progressive systemic sclerosis (PSS) the phenotype frequencies of 28 HLA-A, B, C antigens were determined. Compared to 2947 blood donors the PSS patients exhibited an increase in the HLA-B8 frequency (37% versus 19%). This difference revealed to be not significant after the correction according to the number of antigens tested. The same was with the increase in the frequency of HLA-B5, B13, B27, Cw2 and the decrease in the frequency of HLA-A2, B12, B14, B15, B4 and Cw3. The results were compared with the data reported in the literature. Additionally, there were no differences when compared the diffuse PSS with the acral form and CREST, respectively. PMID- 2920861 TI - [Coexistence of porphyria cutanea tarda and lupus erythematosus]. AB - We report on the appearance of porphyria cutanea tarda in a patient with systemic LE and in two patients with discoid LE. A review is given on the corresponding literature. It is suggested that both lupus erythematosus and porphyria cutanea tarda have multifactorial inheritance. The cause of coexistence can be common genes responsible for the genetic determination which also predispose to the occurrence of both diseases. The question of etiology still remains obscure. This coexistence raises, however, a more practical question as regards the therapeutic modalities for the two diseases. PMID- 2920862 TI - [Anti-psoriasis and phototoxic effect of a hematoporphyrin derivative following topical administration and irradiation with visible light]. AB - An ointment, consisting of 100 micrograms hematoporphyrin derivative +5.0 ml dimethylsulfoxide +95.0 ml Unguentum Alcoholum lanae SR, was checked for both phototoxic and antipsoriatic efficacy. After topical application and irradiation with visible light or ultraviolet radiation, healthy skin showed delayed erythemas, whereas psoriasis plaques improved markedly. PMID- 2920863 TI - Full assessment of the child. PMID- 2920864 TI - Stretching soleus muscle to prevent contractures. PMID- 2920865 TI - Optic neuritis and multiple sclerosis: what is the relationship? PMID- 2920866 TI - Isolated birth injury of the phrenic nerve. PMID- 2920867 TI - Physical therapy for infants with spastic diplegia. PMID- 2920868 TI - Children with preschool minor neurodevelopmental disorders. V: Neurodevelopmental profiles at age 13. AB - A cohort of children diagnosed at age seven as suffering from deficits in attention, motor control and perception was compared at age 13 with a group of children without such problems. More than two-thirds of the index children no longer had any clearly detectable motor problems at 13, but they still had significantly prolonged complex reaction times. These results suggest that children with these deficits in the early school years have a fair biological prognosis by the early teen years. PMID- 2920869 TI - Locomotor strategies preceding independent walking: prospective study of neurological and language development in 424 cases. AB - Locomotor strategies used before the acquisition of independent walking were studied in 424 infants. 270 were survivors of neonatal intensive care (the index group); the other 154 (controls) had had no perintal complications. Five forms of locomotion were distinguished: crawling on hands and knees, creeping on the stomach, bottom-shuffling, other, and none before independent walking. Crawling was the most common form of locomotion in both groups. A higher percentage in the index group were late crawlers (greater than 10 months), but similar proportions in both groups were bottom-shufflers or simply stood up and walked. One of the most important factors influencing locomotor strategies was asymmetry. Analysis of the influence of locomotor strategies on psychomotor and linguistic outcome up to five years showed no significant relationships within the index group. However, within the control group, infants who crawled had a statistically greater incidence of later motor delay, which is in contrast to the findings of other studies. PMID- 2920870 TI - Children with preschool minor neurodevelopmental disorders. IV: Behaviour and school achievement at age 13. AB - A cohort of children with deficits in attention, motor control and perception at seven years, drawn from a total population sample of such children in Goteborg, Sweden, was compared at 13 years with a group of normal children with regard to behaviour and school achievement. The index group showed persisting high rates of severe behavioural problems, as judged by teachers', parents' and self-rating questionnaires. None had been treated with stimulants or other drugs to reduce the symptoms of their neurodevelopmental disorders. It seems that these children's problems were slightly less in the early teen years than they were at 10 years, but the rates were still much in excess of those in the comparison group. PMID- 2920871 TI - The infant motor screen. AB - The authors describe the Infant Motor Screen, which is a brief evaluation of the quality of motor patterns of preterm infants from four to 16 months of age. It was developed for use with an assessment of motor milestones as part of a developmental screening program for high-risk infants. 111 infants were tested at four months and 58 at eight months. The predictive validity for cerebral palsy was high: sensitivity and specificity, respectively, were 0.93 and 0.89 at four months and 1.00 and 0.96 at eight months. Inter-observer agreement was between 0.82 and 0.87 for item scoring and between 0.93 and 1.00 for test rating. PMID- 2920872 TI - Nystagmus after medulloblastoma. AB - Ten survivors of medulloblastoma were examined for residual opthalmological signs. Gaze-evoked nystagmus occurred in six children, four of whom also had pronounced upbeat nystagmus. This is a rare and specific type of nystagmus associated with lesions of the cerebellar vermis and medulla, and has not been described previously as a long-term sequel of medulloblastoma. The recognition of upbeat nystagmus is important because visual acuity may be reduced in upward gaze and difficulties at school may ensue for these children, who may be already intellectually and behaviourally compromised. PMID- 2920873 TI - Cranial ultrasonography in the evaluation of macrocrania in infancy. AB - Cranial ultrasonography was used in the initial evaluation of 40 infants with macrocrania. Three of the infants had normal findings. The other 37 had evidence of various types of abnormality: intraventricular obstructive hydrocephalus, external hydrocephalus, arrested hydrocephalus with atrophy, or mild ventriculomegaly. All the infants were given neurological and developmental examinations at the time of presentation and were followed up for one year. Sonograms and head-circumference and intracranial pressure measurements were done at intervals, according to the initial ultrasound findings and the clinical status of the children. Neurodevelopmental outcome was related to the type of abnormality. The majority of children with external hydrocephalus were neurodevelopmentally normal at follow-up. In contrast, those with obstructive or arrested hydrocephalus had unfavourable outcomes, which may be related to the significant perinatal insult causing the hydrocephalus. CT confirmation was available for 16 of the infants. PMID- 2920874 TI - Long-term prognosis after neonatal tetanus. AB - Twenty-four Turkish children who had had neonatal tetanus were evaluated by means of physical and neurological examinations and psychometric tests at four to 15 years of age. Enuresis, mental retardation and growth retardation were frequent findings. The prevention of neonatal tetanus is important not only because of the high mortality rate but also because of its sequelae. PMID- 2920875 TI - What determines ownership of a cell line? PMID- 2920876 TI - State-dependent hypotonia in posterior cricoarytenoid muscles of the larynx caused by cholinoceptive reticular mechanisms. AB - The neural control of the accessory respiratory muscles regulating upper airway patency is poorly understood. This is particularly true with regard to the declines in electromyographic (EMG) activity of upper airway muscles during sleep. To specify the cellular mechanisms causing decreased upper airway muscle tone during sleep, we used an established pharmacological model of rapid eye movement (REM) sleep. With this model, a REM sleep-like state was reliably produced by microinjecting the cholinergic agonist carbachol directly into the pontine reticular formation of the cat. EMG recording were taken from the posterior cricoarytenoid (PCA) muscles of the larynx during wakefulness and the carbachol-induced, REM sleep-like state. This experimental model had not been previously used to study the neuropharmacological control of the upper airway. The results revealed a dose-dependent decrease in PCA muscle tone caused by pontine microinjections of carbachol. To investigate the cholinergic specificity of these effects, the muscarinic cholinergic antagonist pirenzepine was centrally administered before carbachol. Pirenzepine pretreatment effectively blocked the carbachol-induced, REM sleep-like state and attendant changes in muscle tone. These results specify for the first time that muscarinic cholinergic mechanisms within the pontine reticular formation can causally mediate state-dependent hypotonia in accessory respiratory muscles of the upper airway. PMID- 2920877 TI - Marked increase of cysteine levels in many regions of the brain after administration of 2-oxothiazolidine-4-carboxylate. AB - Although brain cysteine levels can be increased by administration of cysteine, treatment with this amino acid causes toxicity. L-2-Oxothiazolidine-4 carboxylate, a compound in which the thiol group is masked, is effectively transported into the mouse and rat brain. It is converted intracellularly by the action of 5-oxoprolinase into L-cysteine. Study of various regions of the rat brain (cerebellum, hypothalamus, cortex, brain stem, pons, caudate nucleus) showed that the levels of cysteine increased significantly after administration of L-2-oxothiazolidine-4-carboxylate. Glutathione levels were not increased or were only slightly increased under these conditions, reflecting the low rate of glutathione synthesis in many regions of the brain. PMID- 2920878 TI - Stability of the heart rate power spectrum over time in the conscious dog. AB - The purpose of this experiment was to test the stability of the heart rate (HR) power spectrum over time in conscious dogs. HR was recorded for 1 h for each of six animals on 2 days. A Fast Fourier transform was used to derive the HR power spectrum for the 12 contiguous 5-min epochs comprising the 1-h recordings. Changes in frequency and amplitude of the various spectral peaks were quantitatively examined. We confirm the presence of two major concentrations of power centered around 0.02 (low frequency peak) and 0.32 Hz (high frequency peak). However, we observed variations in these spectral peaks, especially their amplitudes, both within each hour and from day 1 to day 2. The amplitudes of these two spectral peaks tended to vary reciprocally. HR power spectra based on 5 min of recorded data were also derived from an additional eight animals in both the lying and standing positions; the power spectra from these short recordings were sufficiently sensitive to detect redistributions in power due to changes in posture in all eight dogs. We conclude that: 1) data should be recorded for relatively long periods (e.g., 1 h) to characterize the HR power spectrum; 2) some variability in frequency and amplitude will persist across spectra even when based on longer data bases; 3) care should be taken to ensure that the subject's behavioral state is stable within the recording period; 4) shorter (e.g., 5 min) data bases are not suitable except for detecting relatively robust changes in the HR power spectrum. PMID- 2920879 TI - Endoscopic management of cysts and pseudocysts in chronic pancreatitis: long-term follow-up after 7 years of experience. AB - Endoscopic cystoenterostomy was performed in 33 patients with chronic pancreatitis. Endoscopic cystoduodenostomy (ECD) was done in 22 cases of symptomatic paraduodenal cysts and endoscopic cystogastrostomy (ECG) in 11 cases of retrogastric pseudocysts. The success rates were 96% for ECD and 100% for ECG. The relapse rate was 9% after ECD and 19% after ECG. No significant complications were observed after successful ECD and clinical relief of pain was achieved in 20 patients. ECD was an effective and definitive treatment for 19 of the 22 cases. Two complications of ECG were gastric hemorrhage and iatrogenic pseudocyst infection. In two ECG patients, percutaneous drainage was required. ECG alone was a definitive treatment for 8 of the 11 cases. When restricted to the precise morphological indication (paraintestinal cyst bulging into the duodenal or gastric lumen), ECD is the first choice for treatment of paraduodenal cysts, whereas ECG is an alternative procedure for the drainage of retrogastric pseudocysts, offering at least results as good as percutaneous drainage. PMID- 2920880 TI - Quantitation of colonic injury from argon laser, neodymium: YAG laser and monopolar electrocautery applied to flat mucosa and small sessile polyps of the canine colon. AB - This study determined the optimum laser energy for ablation of colonic mucosal lesions and small sessile polyps in the canine colon. Neodymium (Nd):YAG laser, argon laser, and monopolar electrocautery were applied to exposed canine colonic mucosa for various application times at various power settings. At the minimum energy level necessary to ablate mucosa, the Nd:YAG laser caused greater muscularis injury than the argon laser and monopolar electrocautery. At higher energy levels, monopolar electrocautery and Nd:YAG laser caused greater muscularis injury than argon laser. Small surgically created polyps in the canine colon were ablated endoscopically with the three energy sources. Single-session complete polyp ablation occurred most frequently with Nd:YAG laser and least frequently with argon laser. The depth of tissue injury beneath polyp ablation sites was least with argon laser and greatest with Nd:YAG laser. This study suggests that the argon laser is safer than the Nd:YAG laser or monopolar electrocautery for coagulation of flat colonic mucosal lesions. Although the argon laser is safer for the coagulation of small sessile colonic polyps, it may be less effective than monopolar electrocautery or the Nd:YAG laser for the single-session fulguration of polyps greater than 5 mm in diameter. PMID- 2920881 TI - Assessment of mucosal hemodynamics in normal human colon and patients with inflammatory bowel disease. AB - Reflectance spectrophotometry measures indices of mucosal hemoglobin concentration (IHB) and oxygen saturation (ISO2). In the rat colon, characteristic patterns of IHB and ISO2 are associated with ischemia with congestion (increased IHB and decreased ISO2) and ischemia without congestion (decreased IHB and decreased ISO2). Endoscopic measurements with acceptable interobserver variability was demonstrated in the canine stomach. In eight healthy subjects, endoscopic measurement in different areas of the colon and rectum revealed significantly lower IHB values in the splenic flexure. These observations are compatible with reduced flow and increased susceptibility to ischemic damage in this watershed area. The endoscopic measurements in 13 patients with active inflammatory bowel disease revealed an increase in IHB and ISO2 values in the involved areas, indicating an increase in mucosal blood flow. In six patients restudied when the disease remitted, these values returned to normal. PMID- 2920882 TI - Diazepam versus midazolam (versed) in outpatient colonoscopy: a double-blind randomized study. AB - Midazolam is a new parenteral benzodiazepine premedication for endoscopy. Consecutive patients were randomized to receive either intravenous midazolam or diazepam as premedication for outpatient total colonoscopy by one endoscopist. Fifty-five patients received diazepam (0.15 mg/kg) and 50 received midazolam (0.07 mg/kg). Both patient and endoscopist were blind to the study drug used. The two groups were similar with respect to age, sex, and indication for colonoscopy. Patients were rated by the endoscopist for degree of cooperation, sedation, and pain during examination. There was significantly more oversedation in the midazolam group than in the diazepam group (p less than 0.05). Immediate procedure recall was less in midazolam patients (p less than 0.005), but on repeat interview the next day there was no difference between the two groups concerning recall of the endoscopy. There was no significant difference between the two groups in the incidence of arm pain. We conclude that in a clinical setting, midazolam does not appear to offer any significant advantage over diazepam, except for cost. Midazolam carries an increased risk of oversedation when it is administered on a milligram per kilogram basis and should instead be titrated individually. PMID- 2920883 TI - Acute gastritis occurring within 24 hours of severe head injury. AB - The purpose of this study was to evaluate the early appearance and incidence of stress gastritis following severe head injury. We performed upper esophagogastroduodenoscopy in 44 patients within 24 hours of a head injury. All patients were comatose and required ventilatory support. Forty of the patients (91%) had gastritis at esophagogastroduodenoscopy. The lesions were distributed in the fundus and corpus of the stomach (77% of the patients), in the esophagus (30% of the patients), in the antrum (25% of the patients), and in the duodenum (7% of the patients). The grade of gastritis at esophagogastroduodenoscopy did not correlate with the severity of the head injury, the type of head injury sustained, the timing of esophagogastroduodenoscopy after head injury, or the presence of shock on admission. However, patients with grade III gastritis had a greater injury Severity Score than patients with grade 0 gastritis (normal mucosa). Gastroduodenal mucosal damage is common after severe head injury and occurs soon after the event. PMID- 2920884 TI - Induced current on the guide wire during sphincterotomy. PMID- 2920885 TI - Endoscopic sphincterotomy in Billroth II patients: an improved method using a diathermic needle as sphincterotome and a nasobiliary drain as guide. PMID- 2920886 TI - Preoperative diagnosis of gallbladder perforation by endoscopic retrograde cholangiography. PMID- 2920887 TI - Changing concepts in the management of pancreatic pseudocysts. PMID- 2920888 TI - Adherent tumor on the tip of the scope. PMID- 2920889 TI - Improving patient tolerance for esophageal laser therapy. PMID- 2920890 TI - Studies on the ignition properties of unipolar and bipolar diathermy probes. PMID- 2920891 TI - Skin tags for the diagnosis of colorectal polyps. PMID- 2920892 TI - Colitis due to strongyloidiasis. PMID- 2920893 TI - Seasonal cycles in testicular activity in the frog, Rana perezi. AB - Studies of seasonal testicular cycle based on spermatogenetic activity and direct measurement of plasma testosterone were made in male frog Rana perezi obtained from its natural biotope in the Iberian Peninsula. Testosterone plasma level was determined by radioimmunoassay and exhibited notable differences according to season: plasma testosterone was lowest (less than 0.5 ng/ml) in summer and then increased progressively to reach a peak in spring (3-4 ng/ml), coincident with mating. After spermiation, when an increase in temperature and photoperiod in the natural habitat occurs, levels decline. Fat bodies also show a pronounced seasonal cycle with total regression following breeding and maximal development in winter. However, testicular weight was independent of seasons, and no significant change was observed throughout the year. Histological evidence indicates that although cell nests of different types are present every month of the year, the most important spermatogenetic activity is initiated in summer. The possible relationship between spermatogenetic activity and testosterone production and the importance of environmental factors as synchronizers of seasonal reproduction are discussed. PMID- 2920894 TI - The effect of severe starvation and captivity stress on plasma thyroxine and triiodothyronine concentrations in an antarctic bird (emperor penguin). AB - The effect of confinement and severe starvation on the plasma thyroxine (T4) and triiodothyronine (T3) concentrations was determined in emperor penguins (Aptenodytes forsteri). During their annual cycle, emperor penguins fast freely for periods of up to 4 months and may thus represent a unique subject to study endocrine adaptations to fasting. Plasma T4 concentrations progressively decreased following capture and confinement of naturally fasting penguins, and within 15-20 days stabilized at levels three times lower than in free-living penguins. A transient fourfold increase in plasma T3 concentration developed within the day following confinement in parallel with a rise in daily body mass loss. Both plasma T3 concentration and mass loss subsided to normal levels within 15 days. The decrease in plasma T4 concentration is in accordance with the well known inhibitory effect of stress on thyroid function in birds and mammals, whereas the transient increase in plasma T3 concentration seems related to enhancement of energy expenditure as a consequence of restlessness. Starvation severe enough to exhaust fat stores and to activate protein catabolism induced a 6- and 5 to 10-fold fall in plasma T4 and T3, respectively. This is in marked contrast with maintenance of plasma thyroid levels during long-term natural fasting associated with protein sparing (R. Groscolas and J. Leloup (1986) Gen. Comp. Endocrinol. 63, 264-274). Surprisingly, there was a final reincrease in plasma T4 concentration in very lean penguins. These results suggest that the effect of starvation on plasma thyroid hormones seems to depend on how much protein catabolism is activated and demonstrate the acute sensitivity of thyroid hormone balance to stress in penguins. PMID- 2920895 TI - Purification and properties of pituitary gonadotropic hormone from Indian teleosts: freshwater murrel (Channa punctatus) and carp (Catla catla). AB - Gonadotropic hormone (GtH) from the pituitaries of two widely different Indian teleosts, a freshwater murrel and a carp, was purified by solvent fractionation, Sephadex G-100 gel filtration, affinity chromatography on concanavalin A Sepharose (Con A-Sepharose), and immunoaffinity chromatography. Elution profile from gel filtration showed three peaks in both cases, peak I and II were clearly separated in murrel but not in carp. Peak II demonstrated strong GtH activity in both murrel and carp but this activity could also be detected in peak I and III of carp. TSH activity was restricted to peak I in murrel and was distributed in all three peaks in carp. Chromatography on Con A-Sepharose was useful in harvesting carp glycoprotein hormones, but gave no advantage in murrel. A pure homogenous GtH from murrel and carp could be obtained by using immunoaffinity chromatography. Polyacrylamide gel electrophoresis of murrel and carp GtH showed a single discrete band. Determination of molecular weight (MW) by Sephadex G-100 gel filtration indicated that murrel and carp GtH were 42,000 and 40,000 Da, respectively. SDS-polyacrylamide gel electrophoresis of murrel and carp GtH revealed two dissimilar subunits, alpha and beta. MW of murrel and carp alpha subunits were 18,000 and 16,000 while those of beta were 27,000 and 26,000 Da, respectively. Comparison of electrophoretic patterns of murrel and carp GtH alpha and beta with ovine LH subunits reveal distinct teleostean GtH subunits. PMID- 2920896 TI - Steroidogenesis in Fundulus heteroclitus. I. Production of 17 alpha-hydroxy,20 beta-dihydroprogesterone, testosterone, and 17 beta-estradiol by prematurational follicles in vitro. AB - In order to understand better the mechanism of gonadotropin action on steroidogenesis in prematurational follicles of Fundulus heteroclitus, follicle synthesis of 17 alpha-hydroxy, 20 beta-dihydroprogesterone (17 alpha-OH,20 beta DHP), testosterone (T), and 17 beta-estradiol (E2) from a variety of precursors and the maturational response of oocytes were simultaneously followed in vitro. The addition of 25-hydroxycholesterol, pregnenolone, or progesterone to unstimulated follicles increased media 17 alpha-OH,20 beta-DHP, T, and E2, as well as oocyte germinal vesicle breakdown (GVBD) in a dose-dependent manner. Inhibition of cholesterol side-chain cleavage by aminoglutethimide blocked 25 hydroxycholesterol-promoted steroid accumulation and GVBD, indicating that 25 hydroxycholesterol does not directly induce GVBD, but rather is metabolized in the follicle to an active steroid (presumably 17 alpha-OH,20 beta-DHP). Likewise, trilostane, an inhibitor of delta 5-3 beta-hydroxysteroid dehydrogenase, blocked pregnenolone action. Both inhibitors also completely abolished steroid accumulation and GVBD promoted by a F. heteroclitus pituitary extract (FPE), but not GVBD induced by exogenous 17 alpha-OH,20 beta-DHP. FPE also significantly depressed T but enhanced E2 production from exogenous precursors. We have concluded from these observations that (1) cholesterol side-chain cleavage and pregnenolone conversion to progesterone are essential for gonadotropin-promoted follicle steroid production and the resulting reinitiation of meiosis by the oocyte, (2) the enzymes necessary for the conversion of cholesterol to 17 alpha OH,20 beta-DHP, T, and E2 are present in the unstimulated, prematurational follicle, and (3) gonadotropin initiates steroidogenesis by acting at a step prior to the conversion of cholesterol to pregnenolone; it also appears to enhance aromatase activity. PMID- 2920897 TI - Vitellogenin induction by estradiol in channel catfish, Ictalurus punctatus. AB - In oviparous vertebrates estrogens induce hepatic synthesis of vitellogenin (VG), a blood protein sequestered in vitellogenic oocytes and from which lipovitellin (LV) and phosvitin are derived. Our objective was to identify VG in the channel catfish, Ictalurus punctatus. An intraperitoneal injection of estradiol-17 beta into adult male fish induced a dose-dependent accumulation of a 150 kDa protein (EP) in the plasma. EP was detectable in Coomassie blue-stained polyacrylamide gels within 24 hr after injection of 2 mg hormone/100 g body weight. During the next 4 days, EP increased from 5 to about 25% of the total plasma protein. Electrophoretic mobility, peptide mapping, and immunological crossreactivity showed EP to be indistinguishable from a plasma protein in adult females with vitellogenic ovaries. Two major yolk polypeptides, YP1 (120 kDa) and YP2 (29.6 kDa), were precipitated by (NH4)2SO4 from a yolk protein extract. YP1 but not YP2 reacted with an anti-EP polyclonal antiserum in Western blots. Peptide mapping after proteolysis with trypsin showed YPs 1 and 2 to be unique and revealed structural homologies between YP1 and EP. Liver but not pancreatic explants from an estradiol-treated male synthesized and secreted a [35S]methionine-labeled, 150 kDa protein beginning about 2 hr after initial exposure to the label. We tentatively conclude that EP and YP1 represent VG and LV, respectively. YP2 remains unidentified. PMID- 2920898 TI - Steroid metabolism in the testes of the breeding and nonbreeding three-spined stickleback, Gasterosteus aculeatus. AB - Steroid metabolism in the testes of sticklebacks was studied in vitro by tissue incubations with [3H]pregnenolone or [3H]androstenedione as precursors. In males in full reproductive condition (nesting), [3H]pregnenolone was mainly converted via progesterone and 17 alpha-hydroxyprogesterone into androstenedione, 11 beta hydroxyandrostenedione, and 11-ketoandrostenedione. The latter was the largest product formed. The main products from the [3H]androstenedione incubation, 11 beta-hydroxyandrostenedione and 11-ketoandrostenedione, confirm these findings. The rate of androgen synthesis, especially of 11-ketoandrostenedione, was much lower after the end of the breeding season. PMID- 2920900 TI - Variations of calcitonin-like immunoreactivity in the crustacean Orchestia cavimana during a molt cycle. AB - The investigation of calcitonin-like immunoreactivity performed in whole extracts of the terrestrial crustacean Orchestia cavimana using radioimmunoassay revealed large amounts of these peptides varying in concentration according to the stages of the molt cycle. Their level is maximum at the time of the exuviation. The results are then discussed regarding the particular calcium metabolism of this species in function of its terrestrial conditions of life. PMID- 2920899 TI - Seasonal variations in testicular germ cell stages and in plasma concentrations of sex steroids in male rainbow trout (Salmo gairdneri) maturing at 2 years old. AB - Male rainbow trout of an autumn- and a spring-spawning strain were sampled every 28 days over a period of 2 years, starting when they were approximately 6 months old. Plasma concentrations of testosterone (T), 11-ketotestosterone (11-K), and 17 alpha,20 beta-dihydroxy-4-pregnen-3-one (17,20 beta-P) were measured by radioimmunoassay. A histometric method was used to determine the absolute quantities of several germ cell stages, including spermatogonia B, spermatocytes, spermatids, spermatozoa, and resorbing spermatozoa. The general pattern of gonadal development in the two strains was similar, e.g., steroids peaking in the order T----11-K----17,20 beta-P. However, there were a large number of differences--in the timing of first appearance of various parameters, in the timing and magnitude of various peaks, in the histological appearance of the regressing testes, and in the heterogeneity of the male population. T and 11-K levels were not associated with any particular germ cell stage in the two strains. Peak 17,20 beta-P levels coincided with the period when ovulated females were present and milt production was maximal. PMID- 2920901 TI - Plasma LH and prolactin levels during the reproductive cycle of the cockatiel (Nymphicus hollandicus). AB - Plasma-luteinizing hormone (LH) and prolactin (Prl) levels were determined using radioimmunoassay during two reproductive cycles in captive cockatiels (Nymphicus hollandicus)--an altricial species in which both parents share incubation and care of young. Birds were stimulated to breed by increasing daylength, light intensity, ambient temperature, and presenting nest boxes. LH levels were elevated during the time of nest inspection in females and peaked during egg laying. In contrast, LH levels were highest in males during nest inspection but were lower during egg laying. In both sexes, LH continued to decline during incubation and care of the young but rose in pairs laying a second clutch. Female and male Prl levels increased during egg laying, peaked during incubation, then declined to egg-laying levels during the nestling stage. Prl continued to decline during the fledgling stage and reached prelaying levels unless a second clutch was begun. In conclusion, in cockatiels, nest inspection and laying are characterized by high LH levels while high Prl levels occur during incubation and feeding of nestlings in both males and females. PMID- 2920902 TI - In vitro effects of cyanoketone and epostane on LH-induced germinal vesicle breakdown in oocytes of Indian major carps. AB - The effect of cyanoketone (inhibitor of delta 5-3 beta-hydroxysteroid dehydrogenase) and epostane (inhibitor of 3 beta-hydroxysteroid dehydrogenase) on LH-induced in vitro germinal vesicle breakdown (GVBD) in the oocytes of Indian major carps, Labeo rohita, Cirrhinus mrigala, and Catla catla, was investigated using five concentrations for each inhibitor. Both of these inhibitors could significantly inhibit the LH-induced GVBD at all of their concentrations in L. rohita and C. catla. However, in C. mrigala, when the oocytes were incubated with cyanoketone or epostane along with LH, the rate of GVBD was not induced significantly at their lowest concentration but four other higher concentrations could inhibit the LH-induced GVBD. A probable mechanism of inhibition of the oocyte maturation by these inhibitors is discussed in the light of available literature. PMID- 2920903 TI - Oxidative metabolism in a teleost, Anabas testudineus Bloch: effect of thyroid hormones on hepatic enzyme activities. AB - In vivo administration of L-thyroxine (L-T4) in Anabas testudineus, while significantly stimulated the activities of cytochrome c oxidase and alpha glycerophosphate dehydrogenase (alpha-GPDH), inhibited glucose-6-phosphate dehydrogenase (G-6-PDH), cytosolic and mitochondrial malate dehydrogenase (cyt. MDH; mit. MDH), and Mg2+ DNP-dependent adenosine triphosphatase (Mg2+ ATPase) activities. The activities of lactate dehydrogenase (LDH), succinate dehydrogenase (SDH), and catalase remained unaltered after L-T4 treatment. Administration of protein synthesis inhibitors such as actinomycin D, while significantly inhibited cytochrome oxidase, alpha-GPDH, catalase, SDH, and Mg2+ ATPase activities, did not change LDH, cyt. MDH, and mit. MDH activities. Chloramphenicol injection significantly stimulated cytochrome oxidase, alpha GPDH, and G-6-PDH activities. Simultaneous injections of actinomycin D or chloramphenicol with 3,5,3'-triiodo-L-thyronine (L-T3) or L-T4 prevented the effects of thyroid hormones on enzyme activities, when compared to the respective controls. PMID- 2920904 TI - The prevention of an acute rise in intraocular pressure following Q-switched Nd:YAG laser iridotomy with clonidine. AB - We evaluated the ability of topical clonidine to suppress an acute rise in postoperative intraocular pressure (IOP) following Nd:YAG laser iridotomy. A total of 36 eyes (29 patients) with chronic primary angle-closure glaucoma underwent Q-switched Nd:YAG laser iridotomy: 18 eyes were treated topically with 0.5% clonidine ophthalmic solution prior to and immediately following the procedure, and a control group of 18 eyes underwent Nd:YAG laser iridotomy without topical clonidine. The control group was selected to match the clonidine treated group in terms of preoperative IOP, the extent of peripheral anterior synechia, and the total amount of laser energy delivered. None of the clonidine treated eyes experienced an IOP rise greater than 4 mm Hg over baseline, whereas 4 of the nontreated eyes (22.2%) developed an IOP rise greater than 10 mm Hg. The mean IOPs were significantly lower during the first 4 h postsurgery in the clonidine-treated eyes. PMID- 2920905 TI - Blood-retinal and blood-aqueous barrier permeability, lens autofluorescence and transmission in insulin-dependent diabetic youngsters. AB - The permeability of the blood aqueous and blood retinal barrier, the lens transmission, and the lens autofluorescence were measured by fluorophotometry in 7 diabetic youngsters treated by conventional therapy (mean age, 10.9 +/- 4.4 years), 9 diabetic youngsters treated by continuous s.c. insulin infusion (mean age, 12.3 +/- 5.0 years), and 13 healthy controls (mean age, 12.4 +/- 5.1 years). The mean permeability value for the blood retinal barrier of the diabetic juveniles did not differ significantly from that of the controls (P greater than 0.4), and no correlation with metabolic control (HbAlc) or duration of diabetes was found (P greater than 0.1). No differences in lens transmission larger than 4% were found. The mean value of lens autofluorescence corrected for normal age dependency was found to correlate with the metabolic control: an increase of mean HbAlc by 1% resulted in an extra increase of autofluorescence by 11% (P = 0.002). This result suggests that good metabolic control can suppress excess lens autofluorescence, a precursor of cataract. PMID- 2920906 TI - The effect of therapeutic ultrasound on the average of multiple intraocular pressures throughout the day in therapy-resistant glaucoma. AB - The effect of therapeutic ultrasound was evaluated in 17 patients with therapy resistant glaucoma by comparing average intraocular pressure (IOP) curves measured before and 3-4 months after insonification. The insonification regimen was standardized; the medication was identical during both pressure curve measurements. The average IOP decrease was 44% +/- 24 SD (range, 73% decrease to 6% increase). In 82% of the patients the IOP decrease was more than 34%. There was no correlation between the percentage of IOP decrease and the average IOP before insonification (correlation coefficient, 0.21; P = 0.41). PMID- 2920907 TI - Bilateral retinopathy and encephalopathy. AB - A 22-year-old woman presenting with recurrent transient episodes of vertebro basilar artery syndrome and blurred vision was initially diagnosed as suffering from a collagen disease affecting the retina and CNS. Treatment with systemic steroids induced an apparent remission. However, a rapid deterioration of her condition prompted a reevaluation of the diagnosis and treatment. Ophthalmoscopic examination disclosed numerous ischemic foci in both eyes, scattered superficial hemorrhages, and neovascular tufts on the optic nerves. The possibility that both the cerebral and ocular phenomena were the results of systemic showering of emboli was raised. Careful two-dimensional echo cardiography revealed a mitral mass compatible with myxoma of the left atrium. The difficult differential diagnosis of combined encephalopathy and retinopathy is discussed. PMID- 2920908 TI - Pattern electroretinogram of the blue cones. AB - In man the electroretinogram to pattern reversal stimuli (P-ERG) represents a cone response of the proximal retina, dominated by the cone mechanisms sensitive to red (R) and green (G). Additionally there is a cone mechanism sensitive to blue (B) which can be studied with and without steady exposure to yellow light. During exposure to a superimposed uniform yellow background (576 nm) the transient P-ERG of the B cones is represented by potentials of small amplitude (less than 1 microV). The latency (peak time) of the response is about 30 ms longer than that of the midspectral (R and G) cones. Furthermore, the P-ERG of the B cones saturates at low luminances and exhibits a maximum amplitude at about 460 nm. Without yellow adaptation, the P-ERG of the B cones can be studied only with low-intensity stimuli of short wavelengths. Near threshold, both the long latency response of the B cones and the short-latency response of the R and G cones are recorded simultaneously, forming a double-peaked wave shape. At suprathreshold luminances, even of short wavelength (435 nm) the P-ERG of the B cones is concealed by the larger short latency response of the midspectral cone mechanism. PMID- 2920909 TI - On the ocular distribution of cardiac glycosides in guinea pigs following acute administration. AB - Tritiated ouabain, digitoxin, and digoxin were given IV to anesthetized guinea pigs. The tritium content of the ocular tissues (cornea, iris, lens, vitreous body, retina, choroid, sclera, and optic nerve) was measured after 1 and 3 h and compared with the amount of tritium found in the brain and some peripheral organs. High levels of digitoxin were found in the brain and retina. Digoxin was detected in large quantities in the retina, but only small levels were found in brain tissue. Ouabain was nearly absent in the retina and cerebrum, whereas in most other ocular and peripheral tissues the three cardiac glycosides were present in comparable quantities. The IP injection of tritiated digoxin resulted in lower absolute tissue levels, but a pattern of distribution similar to that observed in anesthetized guinea pigs was found in conscious animals. PMID- 2920910 TI - The effect of argon laser trabeculoplasty upon the normal human trabecular meshwork. AB - The effect of argon laser trabeculoplasty (ALT) upon the normal human trabecular meshwork, as determined by scanning and transmission electron microscopy is reported. The lower nasal and temporal quadrants of an eye received ALT 5 and 1 day, respectively, prior to enucleation. Laser impact sites were identified as focal disruptions of trabeculae, together with connective tissue and cellular debris. Surviving trabecular endothelial cells near the laser lesions exhibited signs of phagocytic and migratory activity. Exogenous macrophages also contributed to the clearance of debris. Activated trabecular cells were observed leaving the meshwork by migrating over the corneal endothelium. By 5 days post ALT increased amounts of trabeculae lacked an endothelial covering. More activated trabecular cells but fewer macrophages were noted. A laser lesion sited close to Schwalbe's line induced, within 5 days, a local corneal endothelial wave front to advance towards it, thus reflecting many late failed ALT specimens that we have seen. PMID- 2920911 TI - Cellular carbohydrate components in human, rabbit and rat lacrimal gland. Studies using fluorescein and peroxidase labelled lectins. AB - Orbital lacrimal glands from adult male and female rabbits, rats and humans were examined for the presence of intracellular receptors of four lectins: concanavalin-A agglutinin, lutus tetragonolobus agglutinin, ricinus comunis-60 agglutinin and wheat-germ agglutinin using fluorescein-conjugated lectin and peroxidase labelling methods for fluorescence and electron microscopy, respectively. Lectins were used as specific probes to detect carbohydrate moiety of the lacrimal gland. The pattern of labelling with the lectins suggests that N acetyl-glucosamine, N-acetyl-D-galactosamine, D-galactose, D-mannose, sialic acid and L-fucose are contained in the lacrimal gland of the three species. The significance of these findings is discussed. PMID- 2920912 TI - Fine structural defects in a case of congenital microcoria. AB - A case of congenital miosis associated with myopia and cataract is described. Tissue obtained at iridectomy was examined with the electron microscope and compared with a specimen of normal iris. The miotic iris was found to be hypoplastic and to display differences in the cellular density of the stroma. The contractile processes of the dilator myoepithelium were conspicuously absent from the underlying stroma, and the existing myofibrils were much disarranged. PMID- 2920913 TI - The cumulative defect curve: separation of local and diffuse components of visual field damage. AB - We present a new display mode of the results of an Octopus visual field examination, which allows for an easy and reliable assessment of the local and diffuse components of the disturbances of a visual field. Essentially, this display consists of the cumulative distribution of the local defect values. Application to typical cases is discussed. PMID- 2920914 TI - Contact transscleral retinopexy using a sapphire crystal probe. AB - To examine the laser-tissue interactions for contact transscleral irradiation, argon and CW Nd:YAG light was delivered through a synthetic sapphire crystal which was held in direct conjunctival contact perpendicular to the peripheral retina. The threshold for retinal whitening was 0.5 J in the rabbit, 1.0-1.5 J in the monkey, and 1.0-4.0 J in human eyes. Histologic examination of the acute injury and at 2 days, 1, 3, 6, and 12 weeks, showed coagulative lesions centered around the pigmented layers in the rabbit. While severe chorioretinal disruption and hemorrhage did occur depending on species, energy level, and probe location, no scleral perforation was noted at any setting. These preliminary studies suggest that transscleral contact lasers may be used safely in clinical situations where selective ablation of the peripheral retina or pigmented tissues is the primary objective. PMID- 2920915 TI - Effects of non-peptidal CCK receptor antagonist (L-364,718) on pancreatic responses to cholecystokinin, gastrin, bombesin, and meat feeding in dogs. AB - Postprandial pancreatic secretion results from the interaction of neural and hormonal factors but their contribution to the net postprandial secretion is unknown. Recent description of highly specific and potent cholecystokinin (CCK) receptor antagonists allows the determination of the physiological role of CCK in the postprandial pancreatic secretion. In six dogs with chronic pancreatic fistulae, the blockade of CCK receptors by non-peptidal agent (L-364,718) caused little change in basal pancreatic secretion, but decreased significantly (p less than 0.05) by about 60% the pancreatic protein response to meat feeding and virtually abolished the pancreatic responses to CCK-8 and bombesin. The pancreatic protein responses to pentagastrin, reaching about 37% of CCK maximum, was also significantly reduced but this effect was less pronounced than that observed in tests with CCK-8 or bombesin stimulation. In contrast, cholinergically stimulated pancreatic secretion, reaching about 40% of CCK maximum, was unaffected by L-364,718. Cholecystokinin antagonism also failed to affect the postprandial and bombesin induced increments in plasma CCK and gastrin concentrations, but significantly reduced the PP responses to CCK-8 bombesin and meat feeding possibly as a result of the removal of the CCK mediated release of PP. We conclude that CCK plays a crucial role in the mediation of the postprandial and bombesin induced pancreatic secretion and in the PP release. PMID- 2920916 TI - Total protein output during rapid reduction of bile salt secretion rates in man. AB - An investigation was undertaken to study the effect of bile salt secretion on total biliary protein secretion in man. Bile was collected in eight patients from a tube in the bile duct. Collection was started after a meal and continued for six hours, in order to obtain bile salt secretion rates over the entire physiological range. Total protein secretion rates did not vary with change in bile salt secretion or bile flow. The protein pattern assessed by SDS-PAGE did not vary with bile salt secretion. The results indicate that bile salt secretion has little influence on biliary protein secretion under these conditions in man. Changes in bile salt secretion were associated with linear change in bile flow, but there was no relationship between bile flow and protein secretion rates. This argues against convective sieving of plasma proteins into bile. PMID- 2920917 TI - Annular pancreas: a clinical, endoscopic, and immunohistochemical study. AB - A patient with annular pancreas presenting with severe upper abdominal pain is discussed. Endoscopic retrograde cholangiopancreatography (ERCP) was diagnostic, with successful injection of major and minor papillae showing pancreas divisum, an annular duct emptying at the major papilla and changes of severe chronic pancreatitis in all duct systems. Pylorus preserving pancreatoduodenectomy gave complete pain relief. The annulus was shown immunohistochemically to be entirely of ventral gland origin. Chronic pancreatitis was histologically less severe in the dorsal gland. Antegrade dye injection with x-ray showed dorsal to ventral connection in the resected specimen. PMID- 2920918 TI - Cruveilhier-Baumgarten (C-B) disease. AB - A case of Cruveilhier-Baumgarten (C-B) disease is described. It is the first reported from Zambia and from Southern Africa. PMID- 2920919 TI - Adenocarcinoma in Barrett's oesophagus: an overrated risk. AB - Barrett's oesophagus is a risk factor for the development of oesophageal cancer and for this reason annual endoscopic surveillance has been proposed. In this retrospective study of all patients with Barrett's oesophagus diagnosed in a 12 year period carcinoma had developed in only four patients. The incidence of oesophageal cancer in this series was one in 170 patient years, which means a 30 fold increase compared with the general population. The survival of patients with Barrett's oesophagus was not different, however, from an age and sex matched control population. It is concluded that systematic endoscopic surveillance of patients with Barrett's oesophagus is not indicated. PMID- 2920920 TI - Pelvic floor neuropathy. PMID- 2920921 TI - Constancy of glucose and starch fermentations by two different human faecal microbial communities. AB - The fermentation of glucose and corn starch by faecal suspensions from two subjects was examined over a three and a half year period. The substrate specificity and products of the faecal fermentations of each subject were relatively stable during this period and were significantly different between subjects. The major soluble end products of fermentation of glucose or starch were acetate, propionate, and butyrate. Hydrogen temporarily accumulated and was subsequently used in fermentations by both subjects. Hydrogen was used without methane production in fermentations of subject 1, but was used for methane formation in fermentations of subject 2. Although the rates of glucose fermentation were similar between both subjects; subject 1 produced a significantly greater molar ratio of propionate than did subject 2. The rate of fermentation of starch by faecal suspensions from subject 1 was faster than that of subject 2. The molar ratio of butyrate was greater for starch fermentations by subject 2, while the molar ratio of propionate was greater with subject 1. Significant differences were found between subjects in molar ratios and concentration of acetate and propionate and concentrations of butyrate in faeces. PMID- 2920922 TI - Orocaecal transit time in health and in thyroid disease. AB - Altered bowel habit commonly occurs in thyroid disease. We measured orocaecal transit in healthy volunteers and in hyperthyroid and hypothyroid patients before and after treatment, using the lactulose hydrogen breath test incorporating a standard liquid meal to obtain a more physiological assessment. Mean transit time in 12 control subjects was 85 (8) minutes (mean (SE)) (mean coefficient of variation between replicate studies, 8.6% (3%)). In eighteen hyperthyroid patients transit was more rapid at 49 (4) minutes (p less than 0.01). Ten hypothyroid patients had a transit time similar to controls at 91 (9) minutes. Transit time returned to normal in thyrotoxic patients after treatment but in eight hypothyroid patients retested, it remained unchanged. Our findings suggest that (a) the inclusion of a liquid meal provides a reproducible method of measuring orocaecal transit using the lactulose hydrogen breath test, (b) rapid small bowel transit in thyrotoxicosis may be one factor in the diarrhoea which is a feature of the disease and (c) if altered gut transit is the cause of sluggish bowel habit in hypothyroidism, delay in the colon, and not small bowel, is likely to be responsible. PMID- 2920923 TI - Relationships between symptoms, menstrual cycle and orocaecal transit in normal and constipated women. AB - Because severe constipation is a disorder largely confined to young women, the possibility that menstrually related factors contribute to disturbed gastrointestinal motor function has been raised. It has also been reported that normal menstruating women show changes in upper gut transit between the follicular and luteal phases of the menstrual cycle and that patients with constipation show prolonged transit. We therefore studied relationships between symptom severity and orocaecal transit during the menstrual cycle in a group of 14 constipated women and a series of control groups comprising seven normal menstruating women, five postmenopausal women, and eight normal men, to determine whether phases of the menstrual cycle were associated with alteration in symptoms or transit. A regular menstrual cycle was reported by 13 of the 14 patients (range 26-30 days) and by all the menstruating female volunteers. Seven patients noted variation in constipation during the menstrual cycle, in all cases this comprised an improvement in symptoms just before or during menstruation. No consistent relationship between symptom severity and follicular or luteal phase was noted. Repeated orocaecal transit measurements in the four study groups showed no consistent differences (greater than 0.05) between groups or during the menstrual cycle (mean change weeks 1-4, -10 +/- 20 min). These findings are inconsistent with the hypothesis of a progesterone related effect upon orocaecal transit in either normal or constipated women. PMID- 2920924 TI - Intestinal transit in healthy southern Indian subjects and in patients with tropical sprue. AB - Whole gut transit was measured in a group of 21 healthy volunteers and 21 patients with tropical sprue by radio-opaque marker technique, using mean transit time single (MTTS) and single stool transit (SST) method. Mean SST in controls was 25.8 (1.4) (SE) hours, which is considerably shorter than in controls in temperate zones. Mean SST (23.7 (0.6) h) correlated significantly with average MTTS (24.9 (1.6) h) (r = 0.88; p less than 0.001) confirming that SST is a valid method to measure intestinal transit in the tropics. Patients with tropical sprue had a mean SST similar to controls (24.4 (1.1) h), in spite of significantly higher faecal weights (580 (41.2) g v 252 (17.2) g; p less than 0.001). PMID- 2920925 TI - Surface vibration analysis (SVA): a new non-invasive monitor of gastrointestinal activity. AB - A computerised system for measurement of vibration at the abdominal surface was constructed which was addressed to the evaluation of gastrointestinal (GI) motor function. Preliminary studies revealed a dominant low frequency signal which was synchronous with the heartbeat and was considered representative of aortic pulsation. This was excluded by selective spectral filtration. The remaining signal was processed and measured by computer, with provision of quantitative energy values as well as of graphic display. The developed method, called surface vibration analysis (SVA) has been evaluated clinically; (a) against oral to caecal transit times (OCCT) of a standard solid meal, in five patients with severe postgastrectomy diarrhoea, seven patients with mild idiopathic diarrhoea and 22 healthy volunteers. (b) against prokinetic effects of a gastrointestinal stimulant (cisapride) in nine patients. In (a) postprandial SVA energy measurements were greater (SVA [*X (SEM)] = 406,933 (98,224] and oral to caecal transit of the solid meal was more rapid (OCTT = *90 (29) min) in the severe diarrhoea patients [postgastrectomy] than either the mild diarrhoea group (*SVA = 235,317 (50,780); *OCTT = *199 (42) min) or normal volunteers (*SVA = 212,062 (27,153); *OCTT = 242 (19) min) [p less than 0.01 for SVA and OCTT]. In the total group, an inverse correlation was observed between quantitative SVA energy values and oral to caecal transit times of solids (Spearman's rho = -0.486; p less than 0.01). In (b), drug stimulation of the GI tract caused an increase of fasting SVA measurements from *21,217 (5956) [before] to *41,937 (9606) [after] intravenous cisapride (p less than 0.05). This new technique may be useful for evaluation of gastrointestinal motor activity. PMID- 2920926 TI - Abnormal cardiovascular reflexes in patients with gastro-oesophageal reflux. AB - Using five non-invasive tests, abnormalities of cardiovascular reflex function were found in 20 of 50 patients with gastro-oesophageal reflux. Abnormalities of pupil cycle time, an index of non-vagal parasympathetic function, were found in only a few patients, implying that the cardiovascular abnormalities observed were not part of a generalised parasympathetic defect. The findings are consistent with the hypothesis that an abnormality of vagal function may contribute to the pathogenesis of gastro-oesophageal reflux. PMID- 2920927 TI - Smoking delays gastric emptying of solids. AB - Oesophageal transit and gastric emptying of liquids and solids was measured in eight normal subjects with a single test meal containing In113 labelled water and an omelette labelled with Tc99m sulphur colloid. Each volunteer was studied, basally, whilst continuously smoking, and while chewing nicotine gum. Neither liquid, nor solid oesophageal transit were affected by smoking, or gum. Liquid gastric emptying occurred exponentially and clearance was not affected by smoking nor gum (mean basal t1/2 17.4 (2.7) (SEM) min, smoking t1/2 16.6 (7.4) min, gum t1/2 12.5 (2.9) min). Gastric emptying of solid had three components. An initial mean lag phase increased from 17.5 (2.7) min, to 27.5 (6.1) min (p less than 0.05) during smoking, but was not prolonged by nicotine gum (17.5 (1.1) min). A subsequent linear emptying phase was also slowed by smoking from a mean of 1.01 (0.15)% min to 0.80 (0.15)% min (p less than 0.05), but was not affected by nicotine gum, 1.06 (0.2)% min. A third complex phase of solid gastric emptying was not analysed. Smoking delays gastric emptying of solids, but not liquids; nicotine is not responsible for this effect. This observation may partly explain the adverse effect of smoking in patients with gastro-oesophageal reflux. PMID- 2920928 TI - Postprandial antral hypomotility in patients with idiopathic nausea and vomiting. AB - The pathogenesis of idiopathic nausea and vomiting is poorly understood and could involve disorders of gut motility. The contractile activity of the stomach and small bowel was studied in 20 patients (seven men) with nausea and vomiting for longer than six months. None had previous gastric surgery, mechanical obstruction and metabolic causes were excluded. Fasting (four hours) and fed (up to two hours) contractile activity was recorded by a low compliance infusion system from the gastric antrum (four sites), the duodenum and the jejunum. Normal criteria were established in seven healthy controls. During fasting, from one to three (median 2) migrating motor complexes (MMC's) were present in patients and controls. Only two patients had contractile abnormalities during fasting. After a solid-liquid test meal, the contractility of the gastric antrum (quantified electronically as a cumulative motility index for 60 minutes) was significantly impaired in patients (p = 0.012). Six patients had normal qualitative and quantitative antral activity but two of them had 'phrase III-like fasting activity' in the small bowel after the test meal. Postprandial antral hypomotility was identified as a major abnormality in patients with unexplained nausea and vomiting. PMID- 2920929 TI - Pernicious anaemia and Campylobacter like organisms; is the gastric antrum resistant to colonisation? AB - Gastric biopsies from 86 patients with pernicious anaemia were examined for Campylobacter like organisms with particular attention to those showing an antral gastritis in addition to the usual pattern of body gastritis. All the patients had chronic atrophic gastritis in the body but Campylobacter like organisms were found at this site in only three patients. Thus the Type A pattern of gastritis (autoimmune) seen in patients with pernicious anaemia is only rarely associated with Campylobacter like organisms. Forty four of these patients had biopsies from body and antrum, 16 showed an antral gastritis of whom only one had Campylobacter like organism present. Twenty five of this latter group of patients were rebiopsied after five years. There was no change in the pattern of gastritis, and the same single patient remained colonised. The frequency of an antral gastritis in patients with pernicious anaemia was 36% yet the frequency of antral colonisation by Campylobacter like organisms was very low (6%). These results show that, as in the body, Campylobacter like organisms are not associated with gastritis when it occurs at this site in pernicious anaemia. The antral gastritis that may accompany body gastritis in pernicious anaemia seems more likely therefore to be an extension of primary type A body gastritis (autoimmune) rather than a secondary type B (chronic) gastritis and, it is argued, the antrum may exhibit resistance to colonisation. PMID- 2920930 TI - Production of antibodies to gliadin in intestinal mucosa of patients with coeliac disease: a study at the single cell level. AB - Lymphocytes obtained after enzymatic digestion of intestinal biopsies from patients with coeliac disease were examined for the presence of gliadin specific antibody secreting cells by means of the ELISPOT technique. This technique permits enumeration of gliadin antibody secreting immunocytes, differentiated with regard to immunoglobulin class. Patients with coeliac disease were found to have high (834/10(6) cells) numbers of antigliadin spot forming cells (SFC) in gut mucosa. IgG and IgM antigliadin antibody secreting cells were infrequently shown whereas IgA antigliadin SFC predominated in all patients tested (average 68% of total SFC). Ten control patients were investigated in parallel with the coeliac patients and showed only low numbers of gliadin antibody secreting cells in gut mucosa (49/10(6) isolated cells). Antigliadin antibody secretion by peripheral blood mononuclear cells was shown in only two of six coeliac patients tested and in none of the control patients. The findings suggest that the intestinal mucosa is a major site for antigliadin antibody production and that IgA is the dominating Ig-class of these antibodies. The high sensitivity and accuracy of the ELISPOT technique may provide a useful instrument for future studies of antibody production and regulation of the gut immune response to gluten and other alimentary antigens in coeliac and other intestinal diseases. PMID- 2920931 TI - Effect of peritoneo-venous shunt on portal pressure. AB - The cause of variceal bleed after a peritoneo-venous shunt is not known. Portal haemodynamic consequences of a peritoneo-venous shunt are poorly understood. The most critical period after a peritoneo-venous shunt is the early postoperative period when rapid mobilisation of peritoneal fluid occurs. Serial changes in the portal pressure during the early postoperative period have not been recorded. In the present study preoperative wedge hepatic vein (WHV), right atrial (RA) and pulmonary capillary wedged (PCW) pressures, cardiac index (CI), and plasma volume (PV) were measured in five alcoholic cirrhotic patients with tense ascites for up to 20 hours postoperatively. The longterm effect was assessed by repeating the intrahepatic and/or wedged hepatic vein pressures in three of the surviving patients after 10 to 20 months. A significant increase in the circulatory dynamics and portal pressure was seen within two hours after shunt placement. Wedged hepatic vein pressure increased from 27.6 (8.2) mmHg to 37.2 (9.2) mmHg (p less than 0.01), RA pressure increased from 6.8 (1.5) mmHg to 14.0 (4.3) mmHg (p less than 0.05), PCW increased from 7.2 (3.5) mmHg to 19.3 (5.7) mmHg (p less than 0.01), CI increased from 3.4 (0.27) lit/m2/min to 4.3 (0.85) lit/m2/min (p less than 0.05). This was accompanied by a 34% increase in the plasma volume from 1838.5 (142.1) to 2471.4 (210) ml/m2. These derangements were maintained up to 20 hours postoperatively. After 10 to 20 months, repeat measurements revealed a return to preoperative measurements. It is concluded that there is an acute increase portal pressure after a peritoneo-venous shunt attributed to increased circulation plasma volume, resulting from rapid mobilisation of ascitic fluid after the shunt. A sudden increase in portal pressure might be an important provoking factor for variceal bleeding after peritoneo-venus shunt. PMID- 2920933 TI - Looking at HCFA's snapshot of nursing homes. PMID- 2920932 TI - Ursocholic acid: bile acid and bile lipid dose response and clinical studies in patients with gall stones. AB - The biliary bile acid and bile lipid responses to six weeks treatment with approximately 5, 10, and 15 mg/kg/day of ursocholic acid (UCA) were studied in 11 gall stone patients. Maximum enrichment of bile with UCA (24 (SE) 4.9%) occurred with 15 mg UCA/kg/day. The maximum reduction in biliary cholesterol saturation was seen with the 10 mg/kg/day dose when the moles % cholesterol fell from 14 (2.4)% before treatment to 5.6 (0.83)% (p less than 0.02) and the saturation index fell from 1.4 (0.23) to 0.77 (0.13) (p less than 0.05). Clinical studies of the safety and efficacy of UCA in dissolving gall stones were carried out in 13 patients treated for up to two years with a dose of approximately 10 mg/kg/day. Diarrhoea caused withdrawal of treatment in three patients. There were no significant changes in liver function or haematology tests but fasting serum cholesterol tended to rise during treatment. Of nine patients treated for greater than 6 months, only one showed complete gall stone dissolution. As UCA may cause diarrhoea and hypercholesterolaemia, has only a modest effect on biliary cholesterol saturation and low gall stone dissolution efficacy, it is unlikely to replace existing forms of gall stone dissolution therapy. PMID- 2920934 TI - Staying healthy after 85. PMID- 2920935 TI - The incontinency taboo. PMID- 2920936 TI - Paying for long-term care. PMID- 2920937 TI - Dementia and depression: a devastating pair. PMID- 2920938 TI - A past well remembered.... PMID- 2920939 TI - Nurse-managed approach to care. PMID- 2920940 TI - Making the family a partner in quality assurance. PMID- 2920941 TI - Cholesterol reducers. Worth the price? PMID- 2920942 TI - Jack Sprat and all that. PMID- 2920943 TI - Acute care patients also get depressed. PMID- 2920944 TI - What restraint policies don't say. PMID- 2920945 TI - Evidence for the efficacy of adjuvant therapy in epithelial ovarian tumors of low malignant potential. AB - During the 10-year period from January 1975 through December 1985, 48 patients with low malignant potential epithelial ovarian tumors were treated on the Gynecology Service at Memorial Sloan-Kettering Cancer Center. No patients were lost to follow-up and the mean duration of follow-up was 42 months. Twenty-nine patients were Stage I, 5 patients were Stage II, 11 patients were Stage III, 1 patient was Stage IV, and 2 patients were unstaged. Patients were divided into those with no residual disease after initial surgical treatment (29), microscopic residual disease (7), and gross residual disease (12). No patient without residual disease died from cancer. Of the 19 patients with residual disease, all received adjunctive chemotherapy alone, radiation therapy alone, or a combination of both. Three of 19 patients died from cancer. Twelve patients with residual disease were found to be free of disease at second-look surgical reassessment following adjunctive therapy. This review indicates that adjunctive therapy can eradicate residual disease in patients with epithelial ovarian tumors of low malignant potential. PMID- 2920947 TI - 426 cases of stage I endometrial carcinoma: a clinicopathological analysis. AB - Between February 1, 1965, and December 31, 1985, 426 patients affected with Stage I adenocarcinoma of the endometrium were submitted to surgery in the Department of Gynecologic Oncology of the Regina Elena Cancer Institute. The value of the present survey is represented by the homogeneous diagnostic data on the basis of which the treatment was planned. Criteria of histological grading and myometrial invasion were always followed, making it possible to carry out a protocol combining surgery with radiotherapy, chemotherapy, and/or hormone therapy. In fact, an accurate evaluation of the grading, the infiltration of the myometrium, and the localization and size of the lesion are necessary to establish the risk of lymph node invasion. This last parameter is the most important as far as the therapeutic protocol, recurrences, and/or metastases and survival are concerned. The high 5-year survival rate, despite the high average age of the patients (74.7% between the ages of 51 and 70), associated pathologies, and the relatively low incidence of complications from treatment, demonstrate the validity of the protocol adopted. PMID- 2920946 TI - Antiproliferative effect of gossypol and its optical isomers on human reproductive cancer cell lines. AB - The antiproliferative effect of gossypol and its optical isomers on various human cell lines of reproductive and nonreproductive tissue origin was studied. Various reproductive cancer cell lines of ovarian, gestational, and testicular origin were highly sensitive (IC50 values of 0.86-1.98) to gossypol. The antiproliferative action of gossypol was not restricted to reproductive cancers, as non-reproductive cancer cell lines were also equally sensitive (IC50 values of 0.69-3.55). In addition, actively proliferating untransformed cells such as fibroblasts and PHA-activated lymphocytes were also sensitive (IC50 values of 0.87-2.51). (-)-Gossypol was 3.6-12.4 times more potent than (+)-gossypol and 1.48-2.65 times more potent than (+/-)-gossypol. The most sensitive indicator of gossypol action was a decrease in DNA synthesis followed by inhibition of protein synthesis and uptake of rhodamine-123 by mitochondria as tested in an ovarian cancer cell line (OVCA 433) and a fibroblast line (Hs27). These results indicate that gossypol possesses a general nonselective antiproliferative action toward human cells in vitro. Further, the pharmacologic activity of gossypol as an antiproliferative agent is primarily attributable to its (-) isomer, which is also the active isomer as a contraceptive. PMID- 2920948 TI - Synergistic effects of cis-platinum and cytosine arabinoside on ovarian carcinoma cell lines, demonstrated by dual-parameter flow cytometry. AB - Ovarian cancer tends to remain confined to the peritoneal cavity even after widespread dissemination. In order to test the in vitro cytotoxic effect of cis platinum (CP) and cytosine arabinoside (ara-C), a combination which, in theory, is particularly suitable for intraperitoneal (IP) administration, ovarian cancer cells were exposed to each drug alone and in combination and then sampled serially for 336 hr with cell counts and flow cytometry (FCM). We used dual parameter FCM analysis to study changes in DNA and nuclear protein simultaneously. There was good correlation between the degree of cell kill noted in the counts and the duration of observed cytokinetic disturbances in all the treated series. CP and ara-C alone produced temporary cytotoxic and cytokinetic changes. Together, the two agents produced an enhanced CP effect which lasted 336 hr and was accompanied by continued evidence of cell kill in the counts. We conclude that CP and ara-C in vitro act synergistically on ovarian cancer to achieve a high level of cell kill after a single simultaneous application. PMID- 2920949 TI - Endometrial adenocarcinoma histologic subtypes: clinical and pathologic profile. AB - All cases of endometrial adenocarcinoma treated at the Geisinger Medical Center from January 1970 to June 1980 were retrospectively reviewed in an attempt to elucidate the clinical and pathologic profiles of the various histologic subtypes. Complete clinical and pathologic data was available in 418 cases of stage I endometrial adenocarcinoma. The frequency of the histologic subtypes were adenocarcinoma 66%, adenoacanthoma 16%, adenosquamous 5%, papillary 8%, clear cell 3%, and secretory 2%. Absolute 5-year survival was adenocarcinoma 88%, adenoacanthoma 91%, adenosquamous 62%, papillary 63% (P less than 0.01), clear cell 43% (P less than 0.001), and secretory 89%. When comparing the clinical and pathologic profile of the various histologic subtypes, adenosquamous (52%, P less than 0.001) and clear cell (43%, P less than 0.05) were associated with the highest percentage of grade 3 differentiation. Adenosquamous (38%, P less than 0.05) and clear cell (36%) also had the highest percentage of deep myometrial invasion. Papillary subtype (46%, P less than 0.05) was associated with the highest percentage of nulliparity. There was no difference among the subtypes when comparing menopausal status, exogenous estrogen, obesity, hypertension, diabetes, or uterine size. In summary, (1) adenocarcinoma and adenoacanthoma are the most frequent subtypes; (2) adenosquamous, papillary, and clear cell have decreased 5-year survival; (3) the decreased 5-year survival in adenosquamous and clear cell subtypes appears to be associated with increased grade 3 differentiation and deep myometrial invasion while the poor prognosis associated with papillary subtype was not related to grade or myometrial invasion. PMID- 2920950 TI - Complications of combined radical hysterectomy-postoperative radiation therapy in women with early stage cervical cancer. AB - Fifty patients with cervical cancer were treated with radical hysterectomy and lymphadenectomy followed by postoperative radiation therapy for high risk factors (nodal metastases, lymphvascular space invasion, close or involved margins) at the University of Alabama at Birmingham Medical Center from 1969 to 1984. Fifteen (30%) of the patients treated had serious complications, 8 (16%) requiring an operation, and 1 (2%) dying as a result of treatment-related problems. This combined modality approach is associated with significant complications. PMID- 2920952 TI - Radiation treatment of FIGO stage IVA carcinoma of the cervix. AB - Forty-eight patients with FIGO stage IVA cervix cancer were treated with radiation therapy at the Hunter Radiation Therapy Center, Yale--New Haven Hospital from 1966 to 1985. Nine of the 48 patients are alive without recurrence (NED) and the 5-year actuarial survival rate is 18% (+/- 6%, standard error). There was a substantial difference in outcome based on treatment technique. Thirty-five patients were treated with external beam (EB) plus intracavitary (IC) and 8 of these patients (23%) are NED. None of the 12 patients treated with EB alone are alive. One patient treated with preoperative EB plus exenteration is NED. The severe complication rate was 22% and most complications were vesicovaginal fistulas due to successful treatment for bladder involvement. There was a significant difference in survival for patients with minimal parametrial disease (stage IVA1) versus patients with significant parametrial disease (stage IVA2) which was defined as fixation to one or both pelvic sidewalls or hydronephrosis on IVP. The 5-year survival for stage IVA1 disease was 46% (+/- 14%) versus only 5% (+/- 4%) for stage IVA2 disease. Our results indicate that superior survival for stage IVA cervix cancer patients is associated with two factors: minimal parametrial disease and radiation treatment which combines EB plus IC. PMID- 2920951 TI - Intraperitoneal chromic phosphate in ovarian cancer: risks and benefits. AB - Between March 1977 and December 1985, 59 patients were treated with intraperitoneal chromic phosphate at The University of Alabama Birmingham Hospitals and its affiliates. Twenty-seven patients received primary adjuvant therapy. Thirty-two patients were treated "secondarily" after tumor recurrence or after a "positive" second-look laparotomy. Associated morbidity was noted to be 12% with reoperation required in 7%. Early stage and grade tumors demonstrate a good prognosis. Little, if any, benefit was demonstrated in "secondary" therapy of advanced stage and grade tumors. PMID- 2920953 TI - A study of the monoclonal antibody OC 125 to diagnose malignant ovarian tumors. AB - Serum CA 125 was assayed preoperatively in 40 patients with ovarian malignancies and in 44 normal individuals. The correlation between CA 125 and tumor histology, tumor burden, ascites, and the clinical stage was analyzed. CA 125 levels greater than 65 U/ml were defined as positive. The results revealed normal values in each of the 44 normal individuals. CA 125 was elevated in 35 of 40 (87.5%) patients with malignant ovarian tumors including 23 of 24 (95.8%) patients with epithelial ovarian cancers, 7 of whom had stage I disease. Serum CA 125 was also elevated in 12 of 16 (75%) patients with nonepithelial ovarian malignancies. The results suggest that the CA 125 level can be correlated with tumor histology, tumor burden, and ascites but not with clinical stage. PMID- 2920954 TI - Treatment of advanced epithelial ovarian cancer with cisplatin and cyclophosphamide. AB - Between June 1981 and June 1984, 50 patients with stage III or IV epithelial ovarian cancer underwent initial surgery followed by combination chemotherapy with cisplatin 50 mg/m2 iv and cyclophosphamide 500-1000 mg/m2 iv at 28-day intervals. No patients with borderline or well-differentiated tumors were included. If patients were clinically disease-free after 12 cycles of therapy, a second-look laparotomy was performed. A complete response was noted in 12 patients (24%), 11 of whom were surgically evaluated. A partial response was noted in 4 patients (8%), 3 of whom were surgically evaluated. Thirty-four patients (68%) had no response to therapy. The median progression-free survival (PFS) for the entire group was 19.8 months, with a median survival of 27 months. Patients with less than or equal to 2 cm residual disease had a superior median PFS (25.4 months vs 18 months) and median survival (29.4 months vs 19.5 months) to those patients with greater than 2 cm residual disease. Patients who underwent primary debulking had a longer median survival than patients who underwent "interval" debulking after two to four cycles of chemotherapy (29.2 months vs 17.3 months). Thirteen patients (26%) are alive without evidence of disease, 4 patients are alive with disease, and 33 patients are dead of disease. Toxicity was very moderate. In summary, the activity and toxicity of the combination of cisplatin and cyclophosphamide compare favorably to other cisplatin combination regimens. PMID- 2920955 TI - Ovarian clear cell adenocarcinoma. AB - The clinical and pathologic features of 29 cases of ovarian clear cell adenocarcinoma (OCCA) were studied to evaluate outcome and potential predictors of survival. Patients' ages ranged from 30 to 89 years (median, 54 years). The study group, using the FIGO classification, consisted of 10 Stage I, 5 Stage II, 7 Stage III, 5 Stage IV, and 2 unstaged patients. Previous or concurrent endometriosis was noted in 45% of patients. Three patients (10.3%) had hypercalcemia. Only stage and the presence of macroscopic residual disease had a statistically significant association with survival. Stage I and II patients experienced a survival similar to a group of 305 patients with adenocarcinomas of non-clear cell type in our ovarian cancer registry with the exception of the very poor survival among Stage IC OCCA patients. Patients with Stage III and IV OCCA had a worse survival than non-OCCA registry patients of similar stage. Few objective responses to adjuvant chemotherapy could be demonstrated in these high stage OCCA patients. Further study of postoperative adjuvant therapies is warranted. PMID- 2920956 TI - Immune complexes in ovarian carcinoma. AB - Immunodiagnostic screening may improve the survival of ovarian carcinoma by earlier detection and follow-up during treatment. Presently, several ovarian cancer-associated antigens are being utilized to monitor treatment response; a specific and precise test for screening is not currently available. The present study was designed to investigate the presence and clinical significance of circulating immune complexes (IC) in patients with ovarian carcinoma using a polyethylene glycol (PEG) assay. If this assay were to prove clinically useful in patients with ovarian carcinoma, its potential as a screening test would then be evaluated. Serum was obtained from 38 patients with advanced ovarian carcinoma preoperatively, postoperatively, and prior to the administration of a combination chemotherapy regimen containing cisplatin. Five patients had values greater than or equal to 0.10. This test identified only 12.5% of the patients with active disease. Serial sampling failed to reveal any correlation with disease status. Our experience does not support the usefulness of IC levels in studying or treating patients with ovarian carcinoma. PMID- 2920957 TI - Carcinoma of the fallopian tube: clinical management. AB - From 1970 to 1986, 36 women were diagnosed to have primary fallopian tube cancer. Fifty-three percent of the patients were Stage III with a median adjusted survival of 27 months. Although varied adjunctive therapies were employed, none provided a clear survival benefit. Five "second-look" procedures were performed. Only one was negative, occurring in a Stage IIIC patient treated with combination chemotherapy. She has continued without evidence of disease 26 months following diagnosis. Recurrent disease was uniformly fatal, despite efforts at salvage therapy. Disease biology and response to therapy parallels that of similar stage epithelial carcinoma of the ovary. PMID- 2920958 TI - Is subradical surgical treatment for carcinoma of the cervix uteri stage IB logical? AB - Twenty-eight patients with squamous carcinoma of the cervix FIGO stage Ib were treated with three courses of neoadjuvant chemotherapy with a VBP modified scheme. Clinical responses showed that the percentage of complete and moderate responses exceeds 95% of the cases. Clinical response was also related to tumor bulk measurement by ultrasound scanning. Twenty-three of the patients were then subjected to the Wertheim-Meigs operation. Pathological findings of surgical specimens showed absence of residual lesion in 6 patients (26.1%) and carcinoma smaller than 0.5 cm in 5 patients (21.7%). Tumor response to neoadjuvant chemotherapy was excellent in NG3, MG3 tumors when lymphoplasmomonocytic infiltration was present. In accord with this result a new protocol was developed. PMID- 2920959 TI - Estrogen receptors in fine-needle aspirates from metastatic lesions of gynecologic tumors. AB - The estrogen receptor content in metastases of gynecological tumors was analyzed with an immunocytochemical technique in material obtained by fine-needle aspiration. Eighteen patients with metastasis from ovarian (10 cases), endometrial (4 cases), and uterine cervical (4 cases) carcinomas were studied. Three metastases showed specific nuclear staining for estrogen receptors and they originated from primary tumors in the ovary, the cervix, and the endometrium. Thus needle aspirates can be used for cytomorphologic diagnosis as well as determination of estrogen receptors and their use has potential value when a decision must be made between hormonal therapy or chemotherapy in patients with generalized gynecological carcinomas. PMID- 2920960 TI - Therapeutic effect of a radiolabeled monoclonal antibody on human ovarian cancer xenograft in nude mice. AB - The therapeutic value of 131I-OC125, a radiolabeled monoclonal antibody directed against a human ovarian tumor associated antigen CA125, was examined in an ascites forming intraperitoneal human ovarian carcinoma nude mouse model. Nude mice were injected intraperitoneally with NIH:OVCAR3 cells. Twenty-one days after tumor transplantation, groups of animals were injected intraperitoneally as follows: Group 1 with 200 microCi of 131I-OC125 (n = 20), Group 2 with 200 microCi of 131I (n = 17), Group 3 with 200 microCi of 131I-IgG (n = 21), Group 4 with 60 micrograms of OC125 (n = 18), and Group 5 was left untreated (n = 21). Survival of the tumor-bearing animals was used as the endpoint of the experiment. Mean survivals were found to be 52 +/- 18 days for the 131I-OC125 group, 53 +/- 16 days for the 131I-IgG group, 49 +/- 13 days for the 131I group, 47 +/- 24 days for the OC125 group, and 47 +/- 15 days for the untreated control. These results would indicate no therapeutic advantage of 131I-OC125 over controls in this animal model. However, other approaches using single as well as multiple radiolabeled monoclonal antibodies need to be tested in this model in order to definitely establish the efficacy of this treatment modality. PMID- 2920961 TI - Adjuvant chemotherapy in a pregnant patient with endodermal sinus tumor of the ovary. AB - The development of germ cell carcinoma of the ovary during pregnancy is a rare occurrence. Recent advances in chemotherapy have improved significantly the prognosis for patients with early stage disease. Use of cytotoxic agents in pregnancy traditionally has been avoided because of possible teratogenic effects. We describe a pregnant patient who was found to have endodermal sinus tumor of the ovary, stage I, at 13 weeks gestation. She received five courses of adjuvant VAC chemotherapy, beginning with her 17th week of gestation, prior to delivery of a normal infant at term. After an additional seven courses of chemotherapy, a second-look laparotomy revealed no evidence of disease. The infant is developmentally normal at 1 year. A comprehensive review of the literature describing use of chemotherapeutic agents in pregnancy is presented. PMID- 2920962 TI - Carcinoma of the ovary presenting as obstructive jaundice. AB - Obstructive jaundice due to metastatic lymphadenopathy in the region of the common bile duct has been reported in many malignancies, but never previously as the presenting symptom in ovarian cancer. A case in point is presented. PMID- 2920963 TI - Ogilvie's syndrome of colonic pseudo-obstruction: a complication of radical hysterectomy with pelvic and paraaortic lymphadenectomy. AB - Ogilvie's syndrome of colonic pseudo-obstruction has been reported in a wide variety of systemic disorders including blunt and surgical trauma but apparently not as a complication of radical hysterectomy with pelvic and paraaortic lymphadenectomy. Its occurrence following extensive paraaortic dissection in this case but no report so far of its occurrence after routine radical hysterectomy supports the most commonly proposed etiology of disturbed splanchnic nerve supply to the colon as a cause. Colonic pseudo-obstruction following radical hysterectomy with pelvic and paraaortic lymphadenectomy is reported and the etiology, diagnosis, and management are discussed to highlight the condition so that possible associated morbidity/mortality may be avoided. PMID- 2920964 TI - Molar pregnancy coexisting with a normal fetus: a case report. AB - Molar pregnancy with a coexisting live fetus is a rare occurrence. We present morphologic and cytogenetic analysis of a recent case. Cytogenetic studies revealed a 46, XX karyotype for the fetus, the normal placenta, and the abnormal placenta. Chromosome banding studies confirmed the presence of maternal and paternal chromosomes in all three tissues. These studies favored the possibility that both tumor and fetus arose from a single gestation. Subsequently, the patient required chemotherapy for low-risk, metastatic trophoblastic disease. PMID- 2920965 TI - Gynecologic cancer treated with a chemotherapy regimen containing cisplatin. PMID- 2920967 TI - Maternal echocardiography in hypertensive pregnancies. AB - Echocardiographic hemodynamic and left ventricular parameters were determined in 14 normotensive and 18 hypertensive women during the last trimester of pregnancy. The hypertensive patients had significantly higher mean values of total peripheral resistance (p less than 0.001), maximum velocity of posterior wall motion (p less than 0.05), mean velocity of circumferential fiber shortening (p less than 0.01) and percent fiber shortening of left ventricular diameter (p less than 0.05). The mean values for heart rate, stroke volume, cardiac output, cardiac index, left ventricular posterior wall thickness and septal thickness did not differ significantly in both groups. These results reflect increased cardiac contractility related to elevated peripheral vascular resistance in subjects with pregnancy-induced hypertension. PMID- 2920966 TI - Influence of ritodrine on plasma steroids and human placental lactogen levels in third-trimester pregnancies. AB - The effects of ritodrine, administered by intravenous, intramuscular or per os routes, upon plasma levels of unconjugated estriol, estradiol, progesterone and human placental lactogen (HPL) were investigated in 24 third-trimester pregnancies. Ritodrine administered at a constant rate of 200 micrograms/min for 3 h, injected intramuscularly 8 x 10 mg/day for 5 days or given orally in doses of 6 x 20 mg/day for 10 days resulted in a significant decrease in the steroid hormone concentration and a significant elevation of HPL levels. PMID- 2920968 TI - Maternal smoking in relation to the incidence of early neonatal jaundice. AB - A case-control study was carried out to investigate the association between maternal smoking during pregnancy and the risk of early neonatal jaundice. A total of 1,569 cases of neonatal jaundice (2.7% of all singleton births) were identified from the 1984 Washington State birth certificates as having a bilirubin level greater than 10 mg/dl within the first 2 days of life. 2,336 nonjaundiced infants were randomly selected to serve as controls. Information regarding smoking during pregnancy was also obtained from the birth certificates. After excluding infants with known risk factors for neonatal jaundice, 912 cases and 1,752 controls were available for analyses. Infants whose mother smoked cigarettes during pregnancy were at lower risk of neonatal jaundice (odds ratio = 0.81; 95% confidence interval = 0.66-0.99) relative to infants of nonsmokers. This relative risk changed very little after adjusting separately for maternal age, infant's gender, number of prior pregnancies, number of prenatal visits, marital status and number of prior fetal deaths. There was suggestive evidence that this apparent protective effect may be operating only among normal and high birth-weight infants. PMID- 2920969 TI - Uptake of 3H-norepinephrine in different segments of the human non-pregnant and pregnant uterus. AB - Tissue specimens from uterine cervix and corpus of non-pregnant and pregnant women were incubated in vitro in the presence of 3H-norepinephrine. The uptake in the cervix exceeded those of the lower and upper segments of the corpus, and this difference was most pronounced at term pregnancy. The neuronal uptake in the cervix constituted approximately 80% of the total uptake and was higher than in isthmus and fundus (50 and 20%, respectively). The results favour the notion that cervical nerves remain functionally intact throughout pregnancy and support previous histochemical studies demonstrating a segmental difference in uterine innervation and a partial denervation of the myometrium at term. PMID- 2920970 TI - A rabbit model of endometriosis. AB - Since not all problems in endometriosis can be studied in the human, there is need of an animal model. We transplanted endometrial tissue of the rabbit into the peritoneal cavity and studied the changes after 12 weeks. At that time the endometrial implants in the rabbit had become cystic structures. The macroscopic and histologic appearance was consistent with endometriosis. Hormonal supplementation turned out not to be necessary. Microsurgical techniques prevented the formation of tubo-ovarian adhesions. This makes the rabbit model suitable for studying the influence of endometrial implants on fertility. PMID- 2920971 TI - Biophysical and endocrine-metabolic changes during menopausal hot flashes: increase in plasma free fatty acid and norepinephrine levels. AB - Thermocutaneous, vascular, metabolic and hormonal changes were investigated during 11 hot flashes from 6 postmenopausal women. The first detectable change was an increase in finger blood flow with a concomitant enhancement of skin conductance. The increase in skin conductance was followed rapidly by a sharp rise in finger temperature. The main endocrine-metabolic changes associated with the above phenomena were a sharp increase in plasma free fatty acids (approximately 65%), norepinephrine (approximately 100%) and LH (approximately 20%) levels. Plasma glucose and cortisol tended to be increased but did not reach statistical significance; on the other hand, plasma insulin, glucagon, growth hormone, epinephrine and dopamine remained unchanged. PMID- 2920972 TI - Impairment of dopaminergic and opioidergic activity in patients with polycystic ovarian disease is restored by treatment for the induction of ovulation. AB - The luteinizing hormone (LH) response to metoclopramide (MCP), a dopamine receptor antagonist, and naloxone (NAL), an opioid receptor antagonist, was evaluated in 7 patients with polycystic ovarian disease (PCOD) before and during treatment with purified human urinary follicle-stimulating hormone (hFSH), and in 6 control women during spontaneously ovulating cycles. Before treatment, in all patients both MCP and NAL administration did not increase plasma LH levels. In the 6 subjects ovulating following hFSH treatment the LH response to MCP and NAL at preovulatory and midluteal phases was restored, as it occurred in control women. Our results suggest that in PCOD the dopamine and opioid activity in the hypothalamus are decreased. The reversal of peripheral ovarian response induced by treatment for the induction of ovulation may restore these impaired neuroendocrine activities. PMID- 2920973 TI - Epidermal growth factor receptor expression in gynecological malignancies. AB - Epidermal growth factor receptor (IEGF-R) levels were analyzed in 72 gynecological tumor specimens. Measurable EGR-R levels were found in a significant percentage of ovarian and uterine tumors. Moreover, all vulvar epidermoid carcinomas and uterine sarcomas analyzed were EGF-R positive. In all tumor types examined, scattered EGF-R levels were observed. Higher EGF-R levels were found in metastatic than in primary ovarian tumors. Moreover, EGF-R were found to be more expressed in less differentiated than in well-moderately differentiated endometrial tumors. Our results suggest a role of EGF or EGF-like substances in regulating the growth of gynecological malignancies, and indicate EGF-R expression as a possible prognostic factor. PMID- 2920974 TI - 45,XO/46,X,dic(Yq) mosaicism in Turner's phenotype with endodermal sinus tumor of the ovary. AB - A case of a endodermal sinus tumor of the ovary in a patient with 45,XO/46,X,dic(Y) mosaicism is reported because of the rarity of the karyotype and condition. A 15-year-old girl was admitted to Yamagata University Hospital because of constipation for several days. Physical examination showed webbing of the neck, cubitus valgus and short stature. Her abdomen was bulging. Chromosomal analysis showed 45,XO/46,X,dic(Yq) mosaicism in karyotype. alpha-Fetoprotein and CA-125 in the serum were high. A left ovarian tumor was found by laparotomy; however, the right ovary was a streak gonad and the uterus was hypoplastic. An endodermal sinus tumor was diagnosed by a pathologist. After operation, cisplatin vinblastin-bleomycin chemotherapy was instituted and the tumor marker went down. This patient is still healthy and under observation at the outpatient clinic. PMID- 2920975 TI - Menstrual variation of estrogen receptor content in vaginal tissue. AB - Estrogen receptor content in vaginal tissue was quantified in 12 healthy female volunteers during the menstrual cycle. Epithelial biopsies were obtained at cycle days 10 and 21 and investigated by a monoclonal enzyme immunoassay. Measurable amounts of estrogen receptors were found in all women at both sampling occasions. In women with an ovulatory menstrual cycle, a significant fall in V-receptor content was recorded during the luteal phase. Structural and functional changes in the vaginal epithelium during the menstrual cycle may be important for the diagnosis and susceptibility to certain viral infections. PMID- 2920976 TI - Intraperitoneal heparin in peritoneal dialysis and its effect on fibrinopeptide A in plasma and dialysate. AB - In 6 patients on continuous ambulatory peritoneal dialysis we investigated the inhibition of intraperitoneal fibrin formation by heparin. A continuous addition of 500 U of heparin per liter dialysate was used for 52 h. In plasma no heparin activity could be detected, even 52 h after intraperitoneal administration of heparin. The fibrin formation was determined by fibrinopeptide A, a thrombin induced split product of fibrinogen. In patients under regular continuous ambulatory peritoneal dialysis we determined the fibrinopeptide A concentrations in plasma. The values were comparable with the fibrinopeptide A concentrations measured in disseminated intravascular coagulopathy. They decreased during intraperitoneal administration of heparin from 63.2 +/- 11.8 to 4.9 +/- 1.7 ng/ml. The fibrinopeptide A concentration in the 4-hour intraperitoneal dialysate (155.8 +/- 15.7 ng/ml) decreased after heparin administration to 8.5 +/- 2.0 ng/ml and was always higher than in plasma. We conclude that 500 U heparin per liter dialysate prevents the intraperitoneal fibrin formation. The low antithrombin III concentration (0.44 +/- 0.13 mg/dl) in protein-poor dialysate seems to be sufficient to inhibit the thrombin activity after acceleration by heparin. PMID- 2920977 TI - Enhancement of the activation of Glu-plasminogen by urokinase in the simultaneous presence of tranexamic acid or fibrin. AB - The activation rate of Glu-plasminogen (Glu-plg) by urokinase (UK) was enhanced in the presence of either tranexamic acid or fibrin with an increase in the catalytic rate constant (kcat). The maximum increase in kcat was obtained at 0.5 mM of tranexamic acid and 0.1 microM of fibrin. Km did not change. The addition of fibrin to 1 mM tranexamic acid resulted in a further increase in kcat of the UK activation of Glu-plg. On the other hand, the addition of tranexamic acid to 0.1 microM fibrin further increased kcat of the UK activation of Glu-plg. Thus, stimulatory effects were observed on the activation of Glu-plg by UK in the simultaneous presence of tranexamic acid and fibrin. Fibrin-binding sites on the kringle 5 of Glu-plg may be involved in the further increase in the activation rate of Glu-plg by UK in the presence of both fibrin and tranexamic acid in comparison to that in the presence of tranexamic acid alone. Possibly, the Glu plg binding with both tranexamic acid and fibrin (at kringle 5) may be most effectively activated by UK. It is also suggested that two molecules of Glu-plg bind to one molecule of fibrin monomer. PMID- 2920979 TI - [The health reform law under review. Its realization is now underway]. PMID- 2920978 TI - Protein C in the neonatal period. AB - Protein-C activity and antigen were measured in 141 full-term infants during the first month of life. The levels of both protein-C activity and antigen were about one third the level for normal adults in cord blood, and significantly lower than the cord blood during the 1st to 2nd days of life. They increased with age progressively, but did not reach the lowest limit in normal adults even in the first month. The low ratio of protein-C activity and antigen was demonstrated in some infants within the first 4 days of life. The precipitin arc of neonatal infants, which had a discrepancy between protein-C activity and antigen levels, showed an anodal shift upon agarose gel electrophoresis in the presence of Ca2+. The abnormal protein C in the neonatal period may be regarded as protein induced by vitamin-K absence or antagonist. PMID- 2920980 TI - [Growth in the number of physicians and the structure of medical practice. Has the quality of ambulatory care changed?]. AB - In order to realize a good health policy that, over the long term, combines humanity, effectiveness and efficiency, corrections in the evolution of the number of physicians, changes in the structure of practices, and the preservation of quality in ambulatory care are urgent tasks for the remaining decade of this century. In this connection, the development of medical orientational data and the so-called priority health aims, will be of use. In particular, the system of "health-insurance" doctors is threatened by external influences outside the control and authority of the administrative organs concerned. Here, the influence on the overcapacity of doctors arises in the present constitutional provision which states that all those physicians who wish to work within the health insurance system, must be allowed to do so. Owing to the increasing "financial bottlenecks" that health-insurance doctors will encounter, the future practicing physician will increasingly become a "businessman", since rising costs and decreasing turnover will exercise a powerful effect on the doctor's practice. In such a situation new practice structures might have a positive effect. In view of all these factors that threaten the independence of the practicing physician, the difficulty arises of preserving the quality of medical care. Already, attempts are being made, on an "outside the medical profession" basis, to ensure quality control, and the proposals made by the expert councils are an indication that this discussion must be intensified among the medical profession itself. PMID- 2920981 TI - [Arguments for a unified evaluation scale]. PMID- 2920982 TI - [Observations critical of the new evaluation scale]. PMID- 2920983 TI - [Demonstration of a tumor-associated permeability factor in malignant effusions]. PMID- 2920984 TI - [The economics of medical technology in the internist's practice. Current situation and possible alternatives]. PMID- 2920985 TI - [The pathogenesis of multiple sclerosis. Basal membrane injury by persisting viral infection]. PMID- 2920986 TI - [Social relations decisively stamp HIV epidemiology]. PMID- 2920987 TI - [AIDS research. Cooperation is extended]. PMID- 2920988 TI - [Vision disorders with neurogenic causes. Exclusion of ophthalmologic causes- clinic admission is recommended]. PMID- 2920989 TI - [Too thin to work?]. PMID- 2920990 TI - [AZT therapy. Success in HIV-infected children]. PMID- 2920991 TI - Increased tumor necrosis factor production by monocytes in alcoholic hepatitis. AB - Tumor necrosis factor is a cytokine that mediates many of the biologic actions of endotoxin. Recent studies have shown that tumor necrosis factor administration may cause liver injury and that tumor necrosis factor may mediate the lethality of the hepatotoxin galactosamine. One of the most potent inducers of tumor necrosis factor production is endotoxin. Because patients with alcoholic liver disease frequently have endotoxemia and because many of the clinical manifestations of alcoholic hepatitis are known biologic actions of tumor necrosis factor, we thought it would be important to evaluate tumor necrosis factor activity in patients with alcoholic hepatitis. Basal and lipopolysaccharide-stimulated tumor necrosis factor release from peripheral blood monocytes, a major source of tumor necrosis factor production, was determined in 16 patients with alcoholic hepatitis and 16 healthy volunteers. Eight of 16 alcoholic hepatitis patients and only two of 16 healthy volunteers had detectable spontaneous tumor necrosis factor activity (p less than 0.05). After lipopolysaccharide stimulation, mean monocyte tumor necrosis factor release from alcoholic hepatitis patients was significantly increased to over twice that of healthy controls (25.3 +/- 3.7 vs. 10.9 +/- 2.4 units per ml, p less than 0.005). We conclude that monocytes from alcoholic hepatitis patients have significantly increased spontaneous and lipopolysaccharide-stimulated tumor necrosis factor release compared to monocytes from healthy volunteers. We suggest that some of the metabolic abnormalities and possibly some of the liver injury of alcoholic hepatitis may be due to enhanced tumor necrosis factor production. PMID- 2920992 TI - Digoxin-like immunoreactive substances in chronic liver disease. AB - Digoxin-like immunoreactive substances, which cross-react with digoxin antibody, have been found to have natriuretic effect and Na+,K+-ATPase inhibitory effect. The role of digoxin-like immunoreactive substances in chronic liver disease was studied by radioimmunoassay in 63 serum and 60 urine samples from 58 patients with chronic liver disease and compared with 16 controls. Although the mean serum digoxin-like immunoreactive substances level of compensated chronic liver disease patients (0.06 +/- 0.05 ng per ml, p less than 0.01) was higher than that of controls (0.02 +/- 0.03 ng per ml), only four patients had serum digoxin-like immunoreactive substances higher than 0.10 ng per ml. Mean serum digoxin-like immunoreactive substances level was much higher in patients with decompensated chronic liver disease who had ascites (0.32 +/- 0.17 ng per ml, p less than 0.001), hepatorenal syndrome (0.57 +/- 0.20 ng per ml, p less than 0.001) and hepatic encephalopathy (0.43 +/- 0.20 ng per ml, p less than 0.001). Five patients with recent variceal hemorrhage requiring transfusions and saline infusion had significantly increased serum digoxin-like immunoreactive substances (mean: 0.16 +/- 0.06 ng per ml, p less than 0.001) before the development of clinically detectable ascites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2920993 TI - Urea cycle enzyme activities are normal and inducible by a high-protein diet in CCl4 cirrhosis of rats. AB - We produced moderately severe, inactive micronodular cirrhosis in rats using CCl4 and measured the urea cycle enzyme activities in liver after feeding a 15% casein diet for 1 week and again after a 60% casein diet for 1 week. There was no deficiency of any of the five urea cycle enzymes in cirrhotic livers of rats pair fed the 15% casein diet. Argininosuccinate synthetase and carbamyl phosphate synthetase activities were lower than in non-pair-fed controls by some baselines. All five enzymes in cirrhotic livers were induced 1.5- to 3-fold by the high protein diet expressed as units per 100 gm of rat. The level of carbamyl phosphate synthetase activity was lower in the livers of rats pair-fed the 60% casein diet than in control livers based on wet weight, collagen-free protein and DNA, but the activities were equal expressed as units per 100 gm of rat. This example of CCl4-induced cirrhosis in the rat does not serve as a good model for human cirrhosis, in which the urea cycle enzymes are reported to be decreased in activity. PMID- 2920994 TI - Hepatic metabolism of colloidal gold-low-density lipoprotein complexes in the rat: evidence for bulk excretion of lysosomal contents into bile. AB - Rats were treated with 17 alpha-ethinyl estradiol to induce high levels of low density lipoprotein receptors in hepatocytes. When these rats were given intravenous injections of low-density lipoprotein-colloidal gold complexes, most of the gold (labeled with 195Au) appeared to be taken up by Kupffer cells, as were complexes of colloidal gold with albumin or polyvinylpyrrolidone. However, when these rats were also administered gadolinium chloride, which blocks Kupffer cell activity, most of the low-density lipoprotein-gold (but not gold complexed with albumin or polyvinylpyrrolidone) was taken up into hepatocytes by receptor mediated endocytosis and concentrated in peribiliary lysosomes, as determined by electron microscopy. Colloidal gold taken up as a complex with low-density lipoprotein was excreted into the feces via the common bile duct at a maximal rate of about 5% daily, 4 to 12 days after injection. Thereafter, the rate of gold excretion fell off until reaching a plateau after 3 weeks. At this late time, most of the colloidal gold was shown by electron microscopy to be in Kupffer cells, whereas earlier (6 days after injection) it was contained mainly in older hepatocytic lysosomes, identified by lipofuscin granules. It is concluded that, in rats, hepatocytic lysosomes empty most of their contents into bile every week or two, apparently by exocytosis. PMID- 2920995 TI - The effect of biliary enteroenterostomy on the pharmacokinetics of enterally administered cyclosporine in rats. AB - A major factor in poor bioavailability of cyclosporine in children undergoing orthotopic liver transplantation appears to be poor absorption of the drug. Our hypothesis is that the Roux-en-Y choledochojejunostomy used for biliary drainage in these children causes cyclosporine malabsorption by reducing the length of bowel available for absorption and by distally displacing the entry of bile into the intestine. In these experiments, we determined the effect of biliary enteroenterostomy on the pharmacokinetics of enterally administered cyclosporine in Sprague-Dawley rats. Experimental rats (n = 24) were prepared for study by constructing self-emptying jejunal blind loops. Sham rats (n = 9) had jejunal transection and reanastomosis. Control rats (n = 26) had no operation. Two to 4 weeks later, chronic biliary-enteric fistulae were formed in all animals. In experiments, [3H]cyclosporine was delivered into the duodenum while the site of bile delivery varied. Hourly and cumulative [3H]cyclosporine excretion into bile was quantitated, which our preliminary data show to be a valid estimate of absorption. In control rats, bile was delivered into the duodenum or was replaced with saline and sucrose solution. In experimental rats, bile was infused either into the duodenum, which tested bowel shortening only, or into the proximal end of the blind loop, which tested the combined effects of bowel shortening and distal displacement of bile entry. In sham rats, bile was infused into the duodenum, which controlled for previous abdominal surgery, or into the midjejunum, which tested for distal bile entry only. Two effects of biliary enteroenterostomy on cyclosporine absorption were observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2920996 TI - Effects of vitamin E deficiency on hepatic mitochondrial lipid peroxidation and oxidative metabolism in rats with chronic dietary iron overload. AB - Peroxidative decomposition of organelle membrane phospholipids with subsequent organelle dysfunction is a postulated mechanism of liver cell injury in parenchymal iron overload. We studied the effects of different alpha-tocopherol concentrations on hepatic mitochondrial lipid peroxidation and oxidative metabolism in rats with chronic dietary iron overload. There was no evidence of mitochondrial lipid peroxidation (conjugated dienes) or alteration in mitochondrial oxidative metabolism in alpha-tocopherol-deficient rats with normal hepatic iron levels. Significant reductions in mitochondrial respiratory control ratios and oxidative phosphorylation ratios were seen in association with increased conjugated dienes in all three groups of iron-loaded rats regardless of the alpha-tocopherol status (deficient, normal or excess); thus, the alpha tocopherol deficiency associated with dietary iron overload in this experimental model is not responsible for the mitochondrial abnormalities observed. In addition, chronic parenteral administration of alpha-tocopherol to iron-loaded animals, which increased hepatic levels of this substance 3-fold, did not ameliorate the hepatic mitochondrial lipid peroxidation or the defects in mitochondrial oxidative metabolism resulting from iron overload. PMID- 2920997 TI - Stimulation of DNA synthesis in hepatocytes by Kupffer cells after partial hepatectomy. AB - The role of Kupffer cells during reparative regeneration of rat liver was investigated with an in vitro experimental model. Conditioned media from primary cultures of Kupffer cells isolated from intact and regenerating liver were added to primary cultures of hepatocytes, and [3H]thymidine incorporation into DNA was studied. Kupffer cell-conditioned media from intact liver and regenerating remnant liver significantly stimulated DNA synthesis in hepatocytes as compared with control media (p less than 0.05). Moreover, the stimulating activity of Kupffer cells prepared from regenerating liver at 6 and 12 hr after partial hepatectomy was significantly higher than that of Kupffer cells from untreated rats (p less than 0.05). The activity was found in serum-free conditioned media. This stimulating activity exponentially increased as the increase of the number of the cultured cells, indicating that the stimulating activity was released directly by cultured Kupffer cells. These results suggest that Kupffer cells stimulate DNA synthesis in hepatocytes by producing and releasing certain factor(s) at an early stage of liver regeneration after partial hepatectomy. PMID- 2920998 TI - Immunization of experimental animals with dihydrolipoamide acetyltransferase, as a purified recombinant polypeptide, generates mitochondrial antibodies but not primary biliary cirrhosis. AB - The availability of recombinant mitochondrial autoantigens may permit the experimental study of the pathophysiology of primary biliary cirrhosis. Previously, we demonstrated that high-titer antibodies to the 74 kD mitochondrial autoantigen dihydrolipoamide acetyltransferase could be generated when BALB/c mice were immunized with purified recombinant protein. Based on these data, we attempted an 8-month study to induce antibodies and liver dysfunction by immunizing AKR/J, C3H/J and CBA/HeJ mice as well as rats, guinea pigs, rabbits and rhesus monkeys with purified recombinant human dihydrolipoamide acetyltransferase. Antibodies to dihydrolipoamide acetyltransferase were readily induced and detected in all species of experimental animals with species and strain differences in the titer of the responses. Of particular interest, rabbits and guinea pigs produced antibodies which were specifically reactive with the functional site of dihydrolipoamide acetyltransferase, whereas the other strains and species produced antibodies to other epitopes on the molecule. Finally, similar to data on humans with primary biliary cirrhosis, the pyruvate dehydrogenase enzyme pathway was inhibited in the presence of immunized animal sera. These data imply that features other than simply an antibody response to mitochondrial enzymes are required for the development of primary biliary cirrhosis. Further studies will be necessary to determine the mechanisms by which mitochondrial proteins elicit an immune response. PMID- 2920999 TI - Propranolol does not alter cerebral blood flow and functions in cirrhotic patients without previous hepatic encephalopathy. AB - Since it has been suggested that propranolol could lead to hepatic encephalopathy, we undertook a study to assess the effects of propranolol on cerebral blood flow and cerebral functions. Sixteen patients with alcoholic cirrhosis and large esophageal varices and without major hepatic dysfunction (Child-Pugh score less than 14) or previous hepatic encephalopathy were randomized to receive either propranolol or placebo. The following measurements were performed before and 15 min after single intravenous administration of 15 mg propranolol or placebo and again 1 week after chronic oral administration of propranolol 160 mg per day or placebo: cerebral blood flow by the xenon-133 inhalation technique, quantitative electroencephalogram, psychometric test (number connection test), arterial ammonia, pH and pCO2, resting and exercise heart rates (after single administration, electroencephalogram, number connection test and biochemical measurements were not performed). Cerebral blood flow was not significantly modified by treatment (propranolol group: 80 +/- 23 vs. 76 +/- 11 and 83 +/- 9; placebo group: 73 +/- 10 vs. 75 +/- 11 and 81 +/- 18 ml per 100 gm per min, respectively, before and after single and repeated administration). Likewise, neither of the two treatments significantly altered number connection test, quantitative electroencephalogram index, arterial ammonia, pH and pCO2. We conclude that, in this population of cirrhotic patients, propranolol did not alter cerebral blood flow or neuropsychological functions. As a consequence, hemodynamic alterations cannot be considered as causes of possible cerebral side effects of propranolol in cirrhotic patients without severe hepatic dysfunction and previous hepatic encephalopathy. PMID- 2921000 TI - Problems with animal models of chronic liver disease: suggestions for improvement in standardization. PMID- 2921001 TI - Does hypophosphatemia play a role in acute liver failure? PMID- 2921002 TI - Chlamydia trachomatis and ascites: going with the flow? PMID- 2921003 TI - Hyperparathyroidism and portacaval shunt: a syndrome or a coincidence? PMID- 2921004 TI - Quantification of cholesterol nucleation-promoting activity in human gallbladder bile: a "homeopathic" approach? PMID- 2921005 TI - Human embryotoxicity of pyrrolizidine-containing drugs. PMID- 2921006 TI - Acupuncture in epidemic HBV hepatitis: other ritual surgical procedures in Africa as well. PMID- 2921007 TI - Complexities of HBV DNA integration. PMID- 2921008 TI - Chronic lymphocytic leukemia (CLL) in younger adults: a retrospective study of 133 cases. AB - Clinical and biological data have been evaluated, using both univariate and Cox's multivariate statistical analyses, in a series of 133 Chronic Lymphocytic Leukemia (CLL) patients with a mean age of 46.6 years (range 31-50). In univariate analyses, anemia (Hb less than 13 g/dl), peripheral blood (PB) lymphocytosis (greater than 40 x 10(9)/l) and bone marrow (BM) lymphocytosis (greater than 80 per cent) were shown to be of significant prognostic value. Multivariate analysis, through a forward stepwise procedure, showed that the most important and independent variable is the BM lymphocytosis. These results are different from those obtained in previous studies and particularly in a recent identical study performed by the same Cooperative Group on 1777 patients with a mean age of 64.2 years (Mandelli et al., 1987). No significance can be demonstrated in stratifying this series of younger patients according to different staging methods (Rai et al., 1975; Binet et al., 1981b; Mandelli et al., 1987). Therefore this population of CLL patients, with less than 50 years of age, has risk factors quite different from classical CLL. The results of the present study show that the diagnostic approach to B-CLL in younger adults must be more complete: using the common diagnostic criteria, established staging systems appear to be inadequate in this series of younger patients. PMID- 2921009 TI - Diagnostic features and survival in typical and prolymphocytoid variants of chronic lymphocytic leukemia. AB - Diagnostic features were evaluated with regards to survival in 203 cases of typical and prolymphocytoid chronic lymphocytic leukemia. Excluding 27 (13 per cent) patients with second malignancies, survival analyses indicated that the prognostic factors with greatest significance were age at presentation (less than 65 years and 65 years or more: p = 0.0004), proportions of prolymphocytoid cells (less than 10 per cent and 10 per cent or more: p less than 0.0001 age corrected) and surface immunoglobulin (SIg) density (weak and more than weak: p = 0.001 age corrected). In contrast, sex, absolute numbers of prolymphocytoid cells, SIg light chain type and FMC7 expression were not prognostically significant. These observations suggest that the recognition and delineation of prolymphocytoid CLL variants by morphological and immunophenotypic criteria, although important in diagnostic terms, may have less relevance with respect to prognosis and patient management. PMID- 2921010 TI - Retrovirus-associated adult T-cell leukemia-lymphoma: an epidemiologic study of five cases among Hawaii-born offspring of migrant Japanese. AB - Adult T-cell leukemia-lymphoma (ATLL) is a distinct clinicopathologic entity etiologically linked to HTLV-I infection. We have identified five cases of retrovirus-associated ATLL among Hawaii-born first generation offspring (nisei) of migrant Japanese. Four patients were offspring of migrant Japanese (issei) who emigrated to Hawaii from Okinawa, an HTLV-I endemic area. The fifth patient was born of parents who emigrated to Hawaii from Fukushima and Miyagi prefectures, HTLV-I nonendemic areas. Epidemiologic implications and family studies with regard to HTLV-I antibody testing of the index cases are discussed. The high rate of HTLV-I antibody seropositivity among family members and relatives indicates that the risk of acquiring HTLV-I infection and of developing ATLL persists long after migration. Documentation of ATLL among offspring of Japanese immigrants to Hawaii is an important observation because it confirms the potential for long latency between putative exposure to virus and the development of overt disease. Changing marriage patterns among the Hawaii-Japanese may weaken the risk of vertical virus transmission to the descendents of migrants from southern Japan, while increasing the risk to children born of mixed marriages. In addition, blood products derived from high-risk donors will constitute a continuing hazard if they are not subject to screening. PMID- 2921011 TI - Decision-support systems' downfall: management. PMID- 2921012 TI - Greener pastures: knowing when to change jobs. PMID- 2921013 TI - Retirement housing: bigger isn't always better. PMID- 2921014 TI - Substandard care rules would put hospitals at risk. PMID- 2921015 TI - Hospitals support insurance for the working poor. PMID- 2921016 TI - Product-line approach controls cost of providing indigent care. PMID- 2921017 TI - Quality info is free--if you know where to look. PMID- 2921018 TI - To tell the truth, CEOs are valuable witnesses. PMID- 2921019 TI - Psych ads move from scare tactics to education. PMID- 2921020 TI - 'Hotel service' directors gain professionalism. PMID- 2921021 TI - CEO represents hospitals on technology council. PMID- 2921022 TI - Technology, physician supply reshape obstetrics. PMID- 2921023 TI - Public hospitals: health care's safety net. Interview by David Holthaus. PMID- 2921024 TI - Contract management adds value to hotel services. PMID- 2921025 TI - Health care entrepreneur's key to success: break the mold. PMID- 2921026 TI - Competition and culture are slowing HMO growth. PMID- 2921027 TI - Rigid policies can help a plaintiff's case. PMID- 2921028 TI - Lack of complementation between xeroderma pigmentosum complementation groups D and H. AB - The construction of permanent hybrid cell lines between xeroderma pigmentosum (XP) cells from different complementation groups allows analysis not only of the degree of repair correction but also of the restoration of biological activity to the UV-irradiated cells. With use of an immortal human cell line (HD2) that expresses excision repair defects typical of XP group D, a series of permanent hybrid cells has been produced with XP cells from groups A to H. Excision repair, as measured by incision analysis and unscheduled DNA synthesis, is restored to normal or near normal levels in crosses involving HD2 and cells from XP groups A, B, C, E, F, G, and I. All these hybrids show complementation for the recovery of normal UV resistance. As expected, hybrids expressing poor incision and hypersensitivity to UV were produced in crosses between HD2 and XPD fibroblasts, but they were also produced without exception when XPH was the partner. In the permanent HD2 x XPD or XPH hybrids, analysis of incision capacity reveals abnormally low activity and therefore that there has been no complementation. The true hybrid nature of HD2 x XPH cells has been confirmed by HL-A and -B tissue typing; moreover, detailed kinetic analysis of incision in these cells shows that the XPH phenotype, rather than the XPD, is expressed, i.e. breaks accumulate at low UV fluence of 1 J/m2. To help confirm these findings, another immortal XPD cell line was used in fusions involving HD2, XPH, or XPI. Cells resistant to ultraviolet were produced only with XPI fibroblasts. These data are discussed in terms of whether XPD and H mutations are likely to be allelic with respect to incision. PMID- 2921029 TI - Increase of sister chromatid exchanges in excision repair deficient xeroderma pigmentosum. AB - The distribution of spontaneous sister chromatid exchanges (SCEs) was studied in PHA-stimulated lymphocytes from 15 patients affected by xeroderma pigmentosum (XP). The study of unscheduled DNA synthesis (UDS) in twelve of these patients showed that seven were deficient and five proficient. The number of SCEs in XP patient cells was higher than in those of 19 controls, and the distributions of SCEs per cell were significantly different. However, the results varied when XP patients were considered in relation to their UDS: the group of XP patients with proficient UDS did not differ, whereas the group of XP patients with deficient UDS was very significantly different from controls. The group not tested for UDS was similar to the deficient UDS group. The possible relationship between the increase of SCEs and the type of DNA repair defect is discussed. PMID- 2921030 TI - Linkage analysis of the Duffy blood group marker with several chromosome 1 genes in an extended pedigree with Charcot-Marie-Tooth disease. AB - We have recently demonstrated tight linkage of the Duffy blood group marker to the alpha-spectrin gene in an extended pedigree with Charcot-Marie-Tooth neuropathy. To determine a more precise location of the Duffy blood group locus on the chromosome 1 map we have tested several more chromosome 1 genes for linkage with this marker. We found suggestive linkage with the antithrombin III and apolipoprotein A2 genes and conclusive linkage with the gene coding for beta nerve growth factor. PMID- 2921031 TI - Regional localization of the TIMP gene on the human X chromosome. Extension of a conserved synteny and linkage group on proximal Xp. AB - The gene encoding a tissue inhibitor of metallo-proteinases, TIMP, has previously been shown to be X-linked in both the human and mouse genomes. We have used a series of somatic cell hybrids segregating translocation and deletion X chromosomes to map the TIMP gene on the human X chromosome. In combination with previous data, the gene can be assigned to Xp11.23----Xp11.4. Genetic linkage analyses demonstrate that TIMP is linked to the more distal ornithine transcarbamylase (OTC) locus at a distance of about 22 centimorgans. The data are consistent with the conclusion that TIMP maps to a conserved synteny and linkage group on the proximal short arm of the human X chromosome and on the pericentric region of the mouse X chromosome, including loci for synapsin-1, a member of the raf oncogene family, OTC, and TIMP. PMID- 2921032 TI - Expression of fragile sites in human sperm and lymphocyte chromosomes. AB - Sperm and lymphocyte chromosome studies in a normal, fertile male have shown a high degree of coincidence between chromosome lesions and fragile sites in both types of cells. In this donor we also found that some fragile sites expressed in sperm chromosomes coincided with those expressed in lymphocyte chromosomes. These results indicate that the chromosome lesions expressed in sperm do not occur at random and that they are not technical artifacts. The fragility expression in sperm chromosomes could reflect in vivo conditions. The presence in some sperm metaphases of acentric fragments suggests that chromosome fragility can result in the loss of chromosome fragments or give rise to de novo structural rearrangements. However, the incidence of sperm with chromosomal abnormalities observed in this man was within the normal range. PMID- 2921033 TI - Expression of folate-sensitive fragile sites in lymphocyte chromosomes. AB - The expression of folate-sensitive fragile sites (FS) was analyzed using MTX as a fragility inducer in seven normal subjects [four unrelated persons and three members of one family (father, mother, and son)]; a woman heterozygous for fra Xq27.3 with a 47,XXX karyotype; and her son, affected by the fra-X syndrome. The mean expression of chromosome lesions (CL) other than Xq27.3 was 70.1% (686CL in 978 metaphases), and the coincidence between CL and FS was 68.9%. We propose six new c-fra sites: bands 4q33 and 11q22 because they were found in two members of the same family; band 13q32 because it had a frequency of expression of 3% of metaphases; and bands 3p13, 8q21, and Xq21 because they were observed in four of the nine individuals studied. PMID- 2921035 TI - Til 1--a human lymphoblastoid cell line with minimal DNA methylation. AB - Methylation has been shown to be correlated with several fundamental cellular processes, including changes in gene expression, alterations in chromatin structure and inactivation of the mammalian X chromosome. It is possible, therefore, that the methylation status of a particular sequence may reflect involvement in a number of processes. Given this potentially confused situation, it is clear that many studies would be facilitated if unmethylated or minimally methylated DNA from a mammalian source were available. A major use of such DNA would be in the construction of long-range physical maps. In many cases, long range physical maps are a prerequisite for the eventual isolation of disease genes that have been localised to a particular chromosomal region by other means (e.g. genetic linkage studies). Many of the enzymes used in such long-range mapping experiments are methylation sensitive, which makes it difficult to determine how many sites for a particular enzyme are present in any DNA sequence. Here we report the finding of a minimally methylated DNA in the human lymphoblastoid cell line, Til 1. The methylation level of Til 1 DNA was analysed in several ways and compared with that in human lymphocytes, placental tissue and other lymphoblastoid cell lines. The results showed clear and reproducible differences in methylation among the cell types, both at a global level and in the vicinities of specific DNA sequences. Lymphocyte DNA had the highest level of methylation while placental DNA and cell line DNA had lower but similar levels. Til 1 had abnormally low levels of 5-methylcytosine when measured directly, and no detectable methylation at any of the restriction sites examined. PMID- 2921034 TI - Analysis of two 47,XXX males reveals X-Y interchange and maternal or paternal nondisjunction. AB - Two cases of 47,XXX males were studied, one of which has been published previously (Bigozzi et al. 1980). Analysis of X-linked restriction fragment length polymorphisms revealed that in this case, one X chromosome was of paternal and two were of maternal origin, whereas in the other case, two X chromosomes were of paternal and one of maternal origin. Southern blot analysis with Y specific DNA probes demonstrated the presence of Y short arm sequences in both XXX males. In one case, the results obtained pointed to a paracentric inversion on Yp of the patient's father. In situ hybridization indicated that the Y specific DNA sequences were localized on Xp22.3 in one of the three X chromosomes in both cases. The presence of Y DNA had no effect on random X inactivation. It is concluded that both XXX males originate from aberrant X-Y interchange during paternal meiosis, with coincident nondisjunction of the X chromosome during maternal meiosis in case 1, and during paternal meiosis II in case 2. PMID- 2921036 TI - The human homologues of Fim1, Fim2/c-Fms, and Fim3, three retroviral integration regions involved in mouse myeloblastic leukemias, are respectively located on chromosomes 6p23, 5q33, and 3q27. AB - Three mouse genomic domains, Fim1, Fim2, and Fim3, were previously described as proviral integration regions frequently involved in the early stages of myeloblastic leukemogenesis induced in vivo or in vitro by the Friend murine leukemia virus. Fim2 was identified as the 5' end of the c-Fms protooncogene, which encodes the receptor of the macrophage colony stimulating factor (Csflr). The functions of Fim1 and Fim3 are not yet known, but these regions are highly conserved among different species. To examine whether these regions could correspond to known human loci involved in genetic alterations specific to some human leukemias, we undertook their chromosomal mapping. The localization of FIM2/c-FMS on 5q33 was confirmed. FIM1 and FIM3 were localized on human chromosomes 6p22.3-p23 and 3q27 respectively. Interestingly, translocations involving these two regions have been described in various hematopoietic malignancies: the t(6;9)(p23;q34) in acute nonlymphocytic leukemias and the 3q26 q28 translocations in a large variety of leukemias. PMID- 2921037 TI - Incontinentia pigmenti and X-autosome translocations. Non-isotopic in situ hybridization with an X-centromere-specific probe (pSV2X5) reveals a possible X centromeric breakpoint in one of five published cases. AB - Incontinentia pigmenti (IP) is a rare X-linked disease with marked female-to female transmission and a dominant pattern of inheritance. Reports of six unrelated females with IP and X-autosomal translocations, all with the X breakpoint at Xp11, and an additional report of a female with IP and a 45,X/46,X,r(X) karyotype suggests that this may be the locus for the IP gene. When four of these cases, including the r(X), were re-examined with a non isotopic in situ hybridization technique and an X centromere-specific probe (pSV2X5), the Xp11 breakpoint was confirmed. However, results from a fifth reported case, t(X;17), showed that the X breakpoint was within the centromeric alphoid repetitive sequences recognized by the probe pSV2X5. As the clinical presentation of this patient was consistent with the IP phenotype and diagnosis, the centromeric position of the X-chromosome breakpoint raises several questions with respect to the homogeneity of the Xp11 locus for IP. PMID- 2921038 TI - Molecular definition of the 11p15.5 region involved in Beckwith-Wiedemann syndrome and probably in predisposition to adrenocortical carcinoma. AB - To define more precisely, in molecular terms, the region involved in Beckwith Wiedemann syndrome (BWS), we have studied patients with BWS and a constitutional duplication of 11p15 using eight 11p15 markers. In the first case with a de novo duplication and extra material on 11p, the region spanning pter to CALCA, excluded, was duplicated. In the second case, the rearrangement was characterized using somatic cell hybrids established with lymphocytes from the father who carried a balanced translocation t(11;18)(p15.4;p11.1). The breakpoint lay exactly in the same region. It could thus be inferred that the two sons, who were the first cases reported of BWS with dup11p15 and adrenocortical carcinoma (ADCC), carried a duplication similar to that observed in the first case. Together with evidence for specific somatic chromosomal events leading to loss of 11p15 alleles in familial cases of ADCC, it can be hypothesized that a gene involved in predisposition to ADCC maps to region 11p15.5. PMID- 2921039 TI - Linkage of X-linked retinitis pigmentosa to the hypervariable DNA marker M27 beta (DXS255). AB - A hypervariable DNA marker is closely linked to one of the most severe forms of night blindness, X-linked retinitis pigmentosa (RP). Affected individuals with X linked RP, obligate carriers, and ophthalmologically identifiable carriers of the disease were included in a linkage study. The diagnosis was established in five sibships by funduscopic and electrophysiological investigations. When the X linked probe M27 beta was used, 2 recombinants out of 29 informative meioses were detected (theta = 0.07 at a maximum lod of 4.75). The hypervariable probe detected two different alleles in 38 of 39 females tested. M27 beta is therefore a potentially very useful probe for carrier detection and prenatal diagnosis, as well as for addressing the question of heterogeneity of X-linked RP. PMID- 2921040 TI - Demonstration of a Sandhoff disease-associated autosomal 50-kb deletion by field inversion gel electrophoresis. AB - Field inversion gel electrophoresis (FIGE) of SfiI-digested chromosomal DNA was used to demonstrate a 50-kb deletion in one allele of the gene encoding the beta subunit of human hexosaminidase (HEXB at 5q13) of two apparently unrelated patients with Sandhoff disease. In conventional electrophoretic restriction analysis, this deletion was masked by hybridization of bands from the other allele. PMID- 2921041 TI - Nucleolus organizer regions (NORs) inserted in 6q15. AB - We studied a family in which three of the members present one chromosome 6 with an isochromatid gap at the band 6q15 level. Studies of the chromosomes by various banding techniques suggested that the secondary constriction represents a stalk from an acrocentric chromosome inserted into 6q15. The possible influence of the abnormal localization is considered. PMID- 2921042 TI - Duplication of an Xp segment that includes the ZFX locus causes sex inversion in man. AB - Two 46,XY females with tandem duplications of an X short arm segment were studied by cytogenetic and Southern blot analysis. The results show that the duplicated segment in each case included the Xp21.2-Xp22.2 interval, resulting in a double dose of ZFX on the single active X chromosome. The results from our two cases, in conjunction with those reported by other workers, lead us to conclude that the duplication is the reason for the sex inversion. If ZFY and ZFX are indeed sex determining gene loci, these findings favour a model of sex determination characterized by antagonistic interaction between these genes. PMID- 2921043 TI - Genetic polymorphism of human urine deoxyribonuclease I. AB - A genetic polymorphism of human urine deoxyribonuclease I (DNase I) has been detected by the technique of polyacrylamide gel isoelectric focusing (IEF-PAGE) followed by immunoblotting with anti-DNase I antibody. Family studies showed that the three common phenotypes - DNASE1 1, 1-2, and 2 - and the other four rare phenotypes - DNASE1 1-3, 2-3, 2-4, and 3-4 - represent homozygosity or heterozygosity for four autosomal codominant alleles, DNASE1*1, *2, *3, and *4. The frequencies of the DNASE1*1, DNASE1*2, DNASE1*3, and DNASE1*4 alleles in a studied Japanese population were 0.5453, 0.4396, 0.0117, and 0.0034, respectively. PMID- 2921044 TI - A beta-thalassemia mutant caused by a 300-bp deletion in the human beta-globin gene. AB - Larger deletions are a rare cause of beta-thalassemia. We report a further instance of a deletion comprising about 300 bp in a female heterozygote. Exon 1, part of IVS-1 and the 5' beta-globin gene promotor region are lost. PMID- 2921045 TI - Remarks on the article "H-Y antigenicity of human fibroblasts" by C. Jorgensen and E.J. Eichwald. PMID- 2921046 TI - Primary and secondary syphilis, 20 years' experience. 2. Clinical features. AB - The notes of 946 patients with primary and 854 with secondary syphilis were retrospectively reviewed. Of the 184 heterosexual men with primary syphilis, 182 (99%) had chancres affecting the penis, compared with 467 (64%) of the 728 homosexual men (p less than 0.0001). Anorectal chancres occurred in 249 (34%) of homosexual men. The commonest features of secondary syphilis included a rash, lymphadenopathy, and mucous patches of the mouth or genital area. Hepatitis, meningitis, other neurological problems, iridocyclitis, and periostitis were all exceptionally rare. The clinical features of primary and secondary syphilis do not appear to have changed in recent years. PMID- 2921048 TI - Characteristics of inflammatory cells in urethral smears from men with non gonococcal urethritis. AB - Differential cell counts in inflammatory exudates were undertaken in urethral smears from men with non-gonococcal urethritis (NGU) for the first time, recurrent NGU (presumably reinfection) after a new sexual contact, or persistent NGU (in patients with no recent history of sexual exposure). Patients experiencing first episodes of NGU had significantly higher macrophage counts, both in relative and absolute terms, than the other two groups, regardless of the presence or absence of Chlamydia trachomatis in the urethral culture. The estimated total inflammatory cell count (ETICC) in the urethral exudate was assessed by counting the number of inflammatory cells in the first voided urine. The ETICC was significantly lower in patients with persistent NGU but no recent history of sexual exposure than in patients with NGU for the first time or with NGU presumably caused by a new infection. The ETICC in all three groups of patients was significantly higher than in controls. A more precise definition of NGU or more reproducible methods of diagnosis may possibly differentiate patients without an infective cause. PMID- 2921047 TI - Treating genitourinary and pharyngeal gonorrhoea with single dose ceftriaxone. AB - The efficacy of ceftriaxone 250 mg given as a single intramuscular dose to treat genitourinary and pharyngeal gonorrhoea is compared with the outcome of the Danish standard treatment for uncomplicated genitourinary gonorrhoea, pivampicillin 1.4 g and probenecid 1 g, both given by mouth. The study comprised 327 patients for whom the diagnosis of gonorrhoea was made by microscopy of a methylene blue stained smear at their first visit to the clinic and for whom the diagnosis was later confirmed by culture of Neisseria gonorrhoeae. One hundred and seventy patients with genitourinary gonorrhoea (18 with and 152 without concomitant pharyngeal infection) were treated with ceftriaxone. One hundred and fifty seven (17 with and 140 without concomitant pharyngeal infection) were treated with pivampicillin. One week after treatment N gonorrhoeae was isolated from none of 18, 1/152, (1%), 11/17 (65%), and 6/140 (4%) patients, respectively. At a second attendance two weeks after treatment no further treatment failure was found. During the study period, a further 52 patients with pharyngeal infection (with or without concomitant genitourinary infection) that was shown by culture only were treated with a single intramuscular injection of 250 mg ceftriaxone. No treatment failure was observed in this group. Only minor adverse drug reactions were seen. Ceftriaxone 250 mg as a single intramuscular injection is therefore safe and effective in treating gonorrhoea, including pharyngeal infection. PMID- 2921049 TI - Colposcopy, biopsy, and cytology results in women with chlamydial cervicitis. AB - Colposcopy and biopsy were carried out at diagnosis and at follow up of 222 women. Of 322 cervical biopsy specimens taken, 174 were from women with chlamydial cervicitis (patients) and 48 from control women (both at diagnosis) and 100 from 76 patients and seven controls at follow up. Of the 174 patients with chlamydial cervicitis, 158 (91%) had erythema compared with 9/48 (19%) controls, and 140 (81%) had "follicles" and lumps compared with three (6%) controls. The cervical polymorphonuclear leucocyte (PMNL) count in a high power (x 1000) field (HPF) was 85 in patients compared with 47/HPF in controls. Cervical ectopia was found in 154 (89%) patients compared with 32 (67%) controls. After treating the 174 patients, we found erythema in nine (5%) and "follicles" in 16 (9%); both conditions were disappearing. Lymphocytic germinal follicles were found on histology in only 5/165 patients compared with none in controls or in patients at follow up examination (after treatment for chlamydial cervicitis). Inclusions were found in 6/165 patients compared with none in controls or patients at follow up. Chlamydiae were found on electron microscopy in slides from seven out of 159 patients compared with none from controls or 81 subjects at follow up. Estimating numbers of inflammatory cells and measuring vascularity showed diffuse increases in lymphocytes and plasma cells and increases in vascularity in both endocervical and exocervical tissue of patients with chlamydial cervicitis. These increases were lessened by treatment. PMID- 2921050 TI - Bacampicillin to treat non-gonococcal urethritis in men: pilot study. AB - Of 84 men with non-gonococcal urethritis (NGU), 24 yielded Chlamydia trachomatis by either cell culture or MicroTrak immunofluorescence test. All 84 were treated with bacampicillin 800 mg twice a day for seven days. Five (one chlamydia positive) defaulted from follow up 10 to 14 days after the start of treatment. Of the 23 chlamydia positive patients who attended follow up, 22 became chlamydia negative; 14 of the 23 patients also became asymptomatic and had normal urethral smears. Of the 56 chlamydia negative patients who attended follow up, 21 were cleared of their urethritis. Two patients reported side effects; one drowsiness and one mild diffuse alopecia. Bacampicillin may therefore be a safe and effective alternative to tetracycline or erythromycin in treating chlamydial urethritis in men. PMID- 2921051 TI - Value of colposcopy in sexually transmitted diseases clinic based on first year's experience. AB - Two hundred and thirty two patients underwent cervical colposcopy within the first year of establishing a colposcopy service in the sexually transmitted diseases clinic at St Mary's Hospital, London. Their mean age was 27 years. Cervical intraepithelial neoplasia (CIN) was identified in 68 of 81 (84%) patients whose smears showed dyskaryosis and who underwent biopsy. CIN was also detected in 14 of 41 (34%) patients who underwent biopsy and whose repeat smears were reported as giving normal results. The value of assessing two consecutive smears was evident, however, because none of the 99 patients with CIN had two normal smear results consecutively. Patients requiring treatment underwent laser ablation, which was provided in the department of gynaecology. These results show that colposcopy plays a vital part in managing patients with abnormal smears and indicate that genitourinary physicians need to give priority to developing colposcopy services in their specialty. PMID- 2921052 TI - Recognising covert disease in women with chronic vulval symptoms attending an STD clinic: value of detailed examination including colposcopy. AB - A vulval colposcopy clinic was established in the sexually transmitted diseases (STD) clinic of St Mary's Hospital, London, to investigate patients with chronic symptoms (mean duration 3 1/2 years). Fifty patients with a mean age of 33 were studied for 12 months, and a specific diagnosis was established for many of them. Forty complained of pruritus vulvae, 33 of dyspareunia, and 30 of vulvodynia. One or more macroscopic abnormality was seen in 29 of the women, the most common being erythema, papules, plaques, and fissures. Colposcopic abnormalities, however, were identified in 45 of the women, the most common being acetowhite epithelium in a flat, papillary, or cobblestone pattern. Biopsy specimens were obtained from 33 of the patients, and all had abnormal histological features. Those of human papillomavirus (HPV) infection were the most common, and were found in 27 specimens; evidence of vulval intraepithelial neoplasia was seen in seven and that of dermatoses in 10. Further work is required, however, before concluding that HPV was necessarily responsible for the chronic symptoms. PMID- 2921053 TI - Intralesional interferon alfa-2b treatment of condylomata acuminata previously resistant to podophyllum resin application. AB - The safety and efficacy of intralesionally administered interferon alfa-2b were assessed in 11 patients suffering from condylomata acuminata for four to 10 months for whom application of podophyllum resin had proved unsuccessful. Three warts from each patient were injected with 10(6) IU interferon alfa-2b three times a week for three weeks. Treatment was followed by a 13 week observation period. Interferon alfa-2b treatment resulted in a highly significant (p less than 0.0001) reduction in the mean size of the treated warts, which decreased from an initial size of 29 mm2 to 2-3 mm2 by week 16. In six out of the 10 patients completing the trial, both the test condylomata and adjacent control warts cleared completely; a recurrence was observed in one of these six patients. Influenza like symptoms (headache and myalgia) were the most common side effects reported, though they were mild in nature and not disabling. These results corroborate those of previous trials with interferon preparations and indicate that its antiviral activity makes it a possible treatment for this sexually transmitted disorder. PMID- 2921054 TI - Tuberculous cavernositis of the penis: case report. AB - The case of an elderly man with tuberculous cavernositis of the penis leading to distortion and sinus tract formation is reported. The condition resembled carcinoma. Histopathology, a positive tuberculin test result, and a good response to treatment aided in making the diagnosis. PMID- 2921055 TI - Bone invasion in secondary syphilis. PMID- 2921056 TI - Is self application of podophyllin an acceptable treatment of genital warts in men? PMID- 2921057 TI - Transmission of HIV-I from men to women in central Africa. PMID- 2921058 TI - Entropy reduction and decorrelation in visual coding by oriented neural receptive fields. AB - Image coding is optimally efficient if the coefficients of the representation are nonredundant, in the Shannon sense that their mutual information is zero. In that case, the code coefficients are uncorrelated and they form a statistically independent ensemble, so that the conditional probability of one coefficient's value, given any other coefficient's value, is the same as its unconditional probability: P(x/y) = P(x). In order for each coefficient to capture a unique property of the image that cannot be captured by any other coefficient, the expansion functions employed in the code must be linearly independent. In order for the code coefficients to have zero mutual information, the code primitives must be orthogonal so that their projections onto each other are always zero. In biological visual systems, although it is clear that some forms of efficiency (such as speed) are desirable, it is not obvious whether coding efficiency as measured by mutual information among the neurons is a factor which explains any of their properties. The center/surround receptive field profiles of neurons in the retina and geniculate are far from an orthogonal set, but a given neuron can still be regarded as a decorrelator of the incoming signal in the sense that it responds primarily to changes in the image (changes in space, time, chrominance, etc.) At the level of the brain's visual cortex, the introduction of the new variable of orientation selectivity can be regarded not only as a means for providing orientation labels for image structure, but also more basically as an effective decorrelator of the neural representation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2921059 TI - Localized texture processing in vision: analysis and synthesis in the Gaborian space. AB - Recent studies of cortical simple cell function suggest that the primitives of image representation in vision have a wavelet form similar to Gabor elementary functions (EF's). It is shown that textures and fully-textured images can be practically decomposed into, and synthesized from, a finite set of EF's. Textured images can be synthesized from a set of EF's using image coefficient library. Alternatively, texturing of contoured (cartoon-like) images is analogous to adding chromaticity information to contoured images. A method for texture discrimination and image segmentation using local features based on the Gabor approach is introduced. Features related to the EF's parameters provide efficient means for texture discrimination and classification. This method is invariant under rotation and translation. The performance of the classification appears to be robust with respect to noisy conditions. The results show an insensitivity of the discrimination to relatively high noise levels, comparable to the performances of the human observer. PMID- 2921060 TI - Black light: how sensors filter spectral variation of the illuminant. AB - Visual sensor responses may be used to classify objects on the basis of their surface reflectance functions. In a color image, the image data are represented as a vector of sensor responses at each point in the image. This vector depends both on the surface reflectance function and on the spectral power distribution of the ambient illumination. Algorithms designed to classify objects on the basis of their surface reflectance functions typically attempt to overcome the dependence of the sensor responses on the illuminant by integrating sensor data collected from multiple surfaces. In machine vision applications, we show that it is often possible to design the sensor spectral responsivities so that the vector direction of the sensor responses does not depend upon the illuminant. We state the conditions under which this is possible and perform an illustrative calculation. In biological systems, where the sensor responsivities are fixed, we show that some changes in the illumination cause no change in the sensor responses. We call such changes in illuminant black illuminants. It is possible to express any illuminant as the sum of two unique components. One component is a black illuminant. We call the second component the visible component. The visible component of an illuminant completely characterizes the effect of the illuminant on the vector of sensor responses. PMID- 2921061 TI - Fractal character of the auditory neural spike train. AB - Long-counting-time pulse-number distributions (PND's) were measured from a broad variety of cat primary auditory fibers using different tone and noise stimuli, counting times T, and number of samples NT. Whereas short-counting-time PND's (T approximately 50 ms) manifest the presence of spike pairs (an enhancement of even over odd-count probabilities), the irregular shapes of the long-counting-time PND's (T approximately greater than 0.1 s) reveal that the underlying sequence of action potentials consists of spike clusters when viewed on a longer time scale. For all units measured, the count variance-to-mean ratio (Fano factor) F(T) varied little over some 90 dB change in the stimulus level. On the other hand, F(T) increased substantially as T and/or NT were increased, corresponding to the capture of larger and larger spike clusters in the counting time. A relationship is developed between the Fano-time function F(T) and the normalized coincidence rate function, g(tau) versus delay time tau. A plausible form for g(tau) leads to a Fano-time function in good accord with the data. The observed power-law growth of the Fano factor for large counting times [F(T) approximately T alpha where 0 less than alpha less than 1] is accompanied by a power-law decay of the coincidence rate for large delay times [g(tau) approximately tau alpha -1] and a power-law form for the power spectral density at low frequencies [S(f) approximately f -alpha]. The behavior of the PND's and the scale invariance implicit in these fractional-power-law relationships suggest that the neural events on all primary auditory fibers exhibit fractal behavior for sufficiently large times (sufficiently low frequencies). The spike pairs and spike clusters in the PND's are natural consequences of this behavior. The fractal dimension D identical to alpha is estimated to be in the range of 0.3 approximately less than D approximately less than 0.9 for counting times in the range 0.1-10 s. The fractal dimension provides a measure of the degree of event clustering, or irregularity of a sequence of events, that is preserved over different time scales. PND's from low-skew vestibular units, in contrast, do not exhibit fractal behavior. It is suggested that auditory neural-firing patterns may serve to efficiently sample natural fractal noises. PMID- 2921062 TI - Computation of the passive electrical parameters of neurons using a system model. AB - Time-domain analysis of voltage responses to current pulse stimulation has been used to estimate the electrotonic parameters of neurons using the signal model. Errors are likely to accumulate from various steps of the analysis due to noise and electrode artifacts. A system model, which has inherent noise immunity and filtering properties, is presented here. This model employs frequency-domain analysis of the input impedance of a neuronal model (an RC cable). The resistances and capacitances of the system model are estimated from the cell input impedance using an optimization strategy. Using the expression for the input impedance, any specified number of equalizing time constants can be computed exactly. The accessibility to these equalizing time constants 1) provides greater insight into the charge equalization along the length and circumference of the cable, and 2) improves the estimation of all other passive parameters including the electrotonic length. Thus, the system model approach allows information to be extracted more directly and accurately than the signal model approach. PMID- 2921063 TI - A neural network architecture for preattentive vision. AB - Recent results towards development of a neural network architecture for general purpose preattentive vision are summarized. The architecture contains two parallel subsystems, the boundary contour system (BCS) and the feature contour system (FCS), which interact together to generate a representation of form-and color-and-depth. Emergent boundary segmentation within the BCS and featural filling-in within the FCS are herein emphasized within a monocular setting. Applications to the analysis of boundaries, textures, and smooth surfaces are described, as is a model for invariant brightness perception under variable illumination conditions. The theory shows how suitably defined parallel and hierarchical interactions overcome computational uncertainties that necessarily exist at early processing stages. Some of the psychophysical and neurophysiological data supporting the theory's predictions are mentioned. PMID- 2921064 TI - Dynamical neural network organization of the visual pursuit system. AB - The central nervous system is a parallel dynamical system which connects sensory input with motor output for the performance of visual tracking. This paper applies elementary control system tools to extend dynamical neural network models to the visual smooth pursuit system. Observed eye position responses to target motions and characteristics of the plant (eye muscles and orbital mechanics) place dynamical constraints on the interposed neural network controller. In the process of constructing a model for the controller, we show two previous pursuit system models, using efference copy and feedforward compensation, are equivalent from an input-output standpoint. We introduce a controller model possessing a potentially highly parallel implementation and offer an example with supporting neural firing rate data. Changes in time delays or other system dynamics are expected to lead to compensatory adaptive changes in the controller. A scheme to noninvasively simulate such changes in system dynamics was developed. Actual physiologic data of adaptive responses to increased time delay is presented as an example of the utility of this parallel controller. Compensatory changes in our parallel controller model are easily predicted. These results suggest a productive interaction between neural network modeling, neurophysiology, and control systems engineering. PMID- 2921065 TI - Computer vision: a source of models for biological visual processes? AB - This paper reviews some basic computer vision techniques and speculates about their possible relevance to the modeling of human visual processes. Special emphasis is given to image segmentation techniques and how they relate to processes of perceptual organization, such as those embodied in the Gestalt "laws." PMID- 2921066 TI - A hexagonal orthogonal-oriented pyramid as a model of image representation in visual cortex. AB - Retinal ganglion cells represent the visual image with a spatial code, in which each cell conveys information about a small region in the image. In contrast, cells of primary visual cortex employ a hybrid space-frequency code in which each cell conveys information about a region that is local in space, spatial frequency, and orientation. Despite the presumable importance of this transformation, we lack any comprehensive notion of how it occurs. Here we describe a mathematical model for this transformation. The hexagonal orthogonal oriented quadrature pyramid (HOP) transform, which operates on a hexagonal input lattice, employs basis functions that are orthogonal, self-similar, and localized in space, spatial frequency, orientation, and phase. The basis functions, which are generated from seven basic types through a recursive process, form an image code of the pyramid type. The seven basis functions, six bandpass and one low pass, occupy a point and a hexagon of six nearest neighbors on a hexagonal sample lattice. The six bandpass basis functions consist of three with even symmetry, and three with odd symmetry. The three even kernels are rotations of 0, 60, and 120 degrees of a common kernel; likewise for the three odd kernels. At the lowest level, the inputs are image samples. At each higher level, the input lattice is provided by the low-pass coefficients computed at the previous level. At each level, the output is subsampled in such a way as to yield a new hexagonal lattice with a spacing square root 7 larger than the previous level, so that the number of coefficients is reduced by a factor of seven at each level. In the biological model, the input lattice is the retinal ganglion cell array. The resulting scheme provides a compact, efficient code of the image and generates receptive fields that resemble those of the primary visual cortex. PMID- 2921067 TI - Recruitment data for nerve cuff electrodes: implications for design of implantable stimulators. AB - Recruitment characteristics of nerve cuff electrodes implanted in four cats for five months were measured. Monopolar, bipolar, and tripolar configurations were considered. Approximately twice the current was required to achieve a given response using the tripolar configuration as compared with monopolar stimulation. Bipolar stimulation also required more current than monopolar stimulation. Using the recruitment data, a number of strategies for modulating muscle tension were considered. It was shown that both pulse amplitude and pulse duration should be software-selectable to achieve adequate control of muscle tension when using either pulse amplitude modulation or pulse duration modulation. When using pulse amplitude modulation, it was found to be desirable to operate at a low pulse duration in the high end of the allowable range for pulse amplitude. For pulse duration modulation, one should operate at a low pulse amplitude in the high end of the allowable range for pulse duration. The effect of pulse amplitude and pulse duration step size on the maximum step change in muscle tension and the linearity of the recruitment curves were examined. The use of logarithmic steps in the modulation parameter was examined and was shown to result in improved controllability and linearity. PMID- 2921068 TI - Quantitative characterization and sorting of three-dimensional geometries: application to left ventricles in vivo. AB - A procedure for automatic sorting of three-dimensional (3-D) shapes is proposed. The procedure is applied to sort into normal and abnormal categories, human left ventricles (LV) using in vivo data from 19 subjects (ten normal and nine abnormal LV's) studied by ultrafast tomography (Cine-CT). The procedure starts by utilizing a vector in a helical coordinate system to describe the spatial geometry of each individual LV cavity. This individual vector is then anatomically aligned and normalized to eliminate effects due to size, yielding a dimensionless vector, denoted as "geometrical cardiogram" (GCG). The GCG characterizes the instantaneous 3-D geometrical information of the individual LV. For the group of healthy subjects, the Karhunen-Loeve Transform (KLT) is then applied to compress the geometric information contained in their individuals' GCG vectors, at end diastole (ED) and end systole (ES), and yield a unique set of basis vectors. The "normal shape domain" is next defined as a truncated set of the KLT basis vectors from which a normal GCG can be reconstructed with a mean squared error (MSE) smaller than a defined threshold. The calculated MSE of any individual GCG reconstructed in this domain is then used as a criterion for sorting the 3-D shapes. Hearts which yield MSE greater than the threshold are considered abnormal. When applied to the study group of 19 subjects a significant difference (p less than 0.0001) between the MSE values obtained for the normal LV's, and those obtained for the abnormal LV's was detected, thus leading to a successful sorting of all the studied LV's. Finally, the KLT is applied to yield a compact representation of the 3-D geometry of any LV (normal or abnormal). PMID- 2921069 TI - Nonlinear parameter estimation applied to psychophysically measured impulse responses. AB - A technique is presented for the estimation of the impulse response, based on data from a psychophysical experiment on threshold vision. A two-step method is used for the estimation of the model parameters. The first step is a Hankel matrix approach, and the second an unweighted least squares method. Results of this estimation technique are presented. The model with the estimated parameters corroborates other psychophysical data. The estimates obtained are adequate for the intended purposes of simulation and modeling. PMID- 2921070 TI - Distribution models of recirculating lymphocytes. AB - Linear time-invariant, linear time-variant, and linear time-delay models are compared to a more accurate nonlinear model for the distribution of recirculating lymphocytes to various relevant organs of the immune process. The models are based on various degrees of approximation to the complex non-Newtonian tubile flow and tissue diffusion phenomena. PMID- 2921071 TI - Optimization of symptomatic therapy in Parkinson's disease. AB - A third-order nonlinear mathematical model of the dose-effect relationship of levodopa, one of the most common drugs used for the symptomatic therapy of Parkinson's disease, is derived with the aid of a visual tracking based method which allows the measurement of some Parkinsonian symptoms quantitatively and objectively. The parameters of this model are identified for each subject separately due to the large interpatient variability in response to treatment. The model is then used to optimize the dosage regimen for each patient individually (according to the clinical particularities and needs of each patient) with respect to an objective function which includes the symptoms dynamically and the total amount of levodopa which is to be administered. Encouraging clinical results of this control engineering approach to therapy optimization are presented. The advantages and drawbacks of this approach are discussed and further research directions are indicated. PMID- 2921072 TI - Tracking time-varying properties of the systemic vascular bed. AB - The problem of tracking changes in viscoelastic properties of the systemic arterial bed is considered and a recursive estimation procedure, belonging to the class of output-error algorithms with adjustable compensator, is developed and discussed. By means of computer simulations, suitable values are determined for the key design variable which controls the tradeoff between tracking ability and noise sensitivity of the algorithm. In this way, the algorithm allows on-line estimation of arterial compliance, peripheral resistance, and characteristic impedance on the basis of aortic pressure and flow signals. Furthermore, the results obtained from data numerically simulated, as well as measured on a mock circulatory system, demonstrate that the dominant arterial time-constant can be tracked by the algorithm using only measurements of the aortic pressure during diastole. PMID- 2921073 TI - Source parameter estimation in inhomogeneous volume conductors of arbitrary shape. AB - In this paper it is demonstrated that the use of a direct matrix inverse in the solution of the forward problem in volume conduction problems greatly facilitates the application of standard, nonlinear parameter estimation procedures for finding the strength as well as the location of current sources inside an inhomogeneous volume conductor of arbitrary shape from potential measurements at the outer surface (inverse procedure). This, in turn, facilitates the inclusion of a priori constraints. Where possible, the performance of the method is compared to that of the Gabor-Nelson method. Applications are in the fields of bioelectricity (e.g., electrocardiography and electroencephalography). PMID- 2921074 TI - Parametric modeling of somatosensory evoked potentials. AB - In this paper, we examine methods of characterizing somatosensory evoked potentials (SEP's) in both the time and frequency domains. We have found that the truncated impulse response (TIR) method produced an accurate time domain model of the SEP signals at model orders greatly reduced from the original state space matrix. The TIR method was valuable for smoothing signals that were slightly corrupted by noise. In this case, the simulated data sequence was close to the original data sequence in the mean squared error sense. For signals that were greatly corrupted by noise, the TIR method was not able to perform as well. Therefore, the TIR method was not a feature extraction method but was valuable for data simulation. In the frequency domain, we have used the autoregressive moving average model (ARMA) to parameterize the SEP signal. An overdetermined set of Yule-Walker equations was created to determine the autoregressive (AR) parameters of the original data with the model order established by the singular value decomposition. From these AR parameters, a residual time series was generated which was used to find the moving average parameters. The resulting ARMA model was used to produce a simulated data sequence. The frequency domain characteristics of the simulated sequence and the corresponding power spectral density of the ARMA filter were very close to the periodogram of the original data sequence. Accurate parameterization was achieved for the SEP waveforms at low filter lengths. PMID- 2921075 TI - Federal commission on nursing: final report. PMID- 2921076 TI - Physiological mechanisms for calcium-induced changes in systemic arterial pressure in stable dialysis patients. AB - The mechanisms by which variations in blood ionized calcium (Ca2+) influence systemic arterial pressures independent of changes in extracellular fluid volume, pH, and electrolytes are unknown. To study this issue, we dialyzed eight stable hemodialysis patients on three separate occasions during 1 week with dialysates differing only in calcium concentration. Ultrafiltration was adjusted to achieve the patient's estimated dry weight. Postdialysis Ca2+ was measured, as were arterial blood gases, electrolytes, magnesium, blood urea nitrogen, creatinine, and hematocrit. Blood pressures and two-dimensional, targeted M-mode echocardiograms were recorded with the patient in the supine position after 15 minutes of rest. Postdialysis, three different levels of Ca2+ were achieved. Other measured biochemical variables and body weight did not differ among the three study periods. Changes in Ca2+ correlated directly with changes in systolic, diastolic, and mean blood pressures, left ventricular stroke volume, and cardiac output. In contrast, heart rate, left ventricular end-diastolic dimension, and total systemic vascular resistance were not altered significantly by changes in Ca2+. Thus, alterations in Ca2+ within the physiological range affect systemic blood pressure primarily through changes in left ventricular output rather than in peripheral vascular tone in stable dialysis patients. PMID- 2921077 TI - Effect of oral calcium on blood pressure response in salt-loaded borderline hypertensive patients. AB - To clarify the mechanism of the antihypertensive effect of oral calcium loading, we studied the effect of low versus high calcium intake on salt-induced blood pressure elevations in patients with borderline hypertension. After a 7-day period of dietary salt restriction (50 meq/day), 27 patients were placed on a high salt (300 meq/day), low calcium (250 mg/day) diet for 7 days; 14 of these patients were given 2,160 mg/day of supplementary calcium (Ca group), and 13 patients were given placebo (non-Ca group). With a high salt intake, the percent increase in mean blood pressure was smaller in the Ca group than in the non-Ca group (+2.85 +/- 1.22% vs. +8.63 +/- 1.66%, respectively, p less than 0.01). The Ca group showed a smaller weight gain (p less than 0.05) and a greater urinary excretion of sodium (p less than 0.005) than the non-Ca group. In the Ca group, but not in the non-Ca group, high salt intake resulted in an increase in intraerythrocyte magnesium content (p less than 0.01), which was correlated inversely with the salt-induced changes in mean blood pressure (r = -0.54, p less than 0.05). While the increase in cellular magnesium was greater in the Ca group, the changes in red blood cell sodium and sodium/potassium ratio were not different between the two groups. The results suggest that oral calcium supplementation may prevent a rise in blood pressure in patients on a high salt, low calcium diet by attenuating the sodium retention.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2921078 TI - Sequential changes of cerebrospinal fluid sodium during the development of hypertension in Dahl rats. AB - The role of sodium retention and consequent changes in cerebrospinal fluid sodium concentration in the genesis of hypertension in Dahl rats was evaluated. Dahl salt-sensitive (DS, n = 7), Dahl salt-resistant (DR, n = 7), and Sprague-Dawley (n = 6) rats were housed in metabolic cages and instrumented with a stainless steel cannula in the cisterna magna and a femoral arterial catheter. A blood sample was drawn daily (200 microliters), and cerebrospinal fluid was collected by continuous 24-hour withdrawal (200 microliters/day). Daily sodium, potassium, and water balances were also determined. Rats were studied sequentially on 0.4%, 4%, and 8% sodium diets (7 days per sodium level). Mean arterial pressure increased with 4% NaCl from 107 to 120 mm Hg (p less than 0.05) over 24 hours in DS rats and remained at about that level until the NaCl was increased to 8%, which resulted in a gradual rise of mean arterial pressure over the next 7 days to 135 mm Hg. Cerebrospinal fluid sodium was unchanged in DR and Sprague-Dawley rats fed 4% or 8% sodium, but in DS rats rose from 152.3 to 155.2 +/- 0.6 meq/l on the third day at 4% sodium and remained elevated over the next 2 weeks of study. Blood sodium was unchanged throughout the study in all groups. On the first day only of the 4% and 8% sodium diets, both DS and DR rats exhibited a similar net retention of sodium, which was greater than the Sprague-Dawley rats (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2921079 TI - Norepinephrine release and reuptake by hypothalamic synaptosomes of spontaneously hypertensive rats. AB - We compared the overflow of endogenous norepinephrine during electrical field stimulation, the norepinephrine content, and the rate of initial neuronal uptake of [3H]norepinephrine in synaptosomes isolated from hypothalamus and brainstem of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats at 7 and 13 weeks of age. The synaptosomes of two rats, a SHR and a WKY rat control, were simultaneously processed and subjected to the same electrical field stimulation. The overflow of endogenous norepinephrine during electrical stimulation (2 Hz, 2 minutes) in the hypothalamic synaptosomes of 7-week-old SHR was significantly greater, whereas the overflow of 13-week-old SHR was equivalent to the age matched WKY rat. The norepinephrine content of synaptosomes was about the same in SHR and age-matched controls. There was also significantly enhanced [3H]norepinephrine uptake in the hypothalamic synaptosomes of young SHR, but neither the hypothalamic nor the brainstem samples of 13-week-old SHR showed any significant difference in their rate of [3H]norepinephrine uptake. These data are similar to those we observed (unpublished observations) in perfused mesenteric artery system in which norepinephrine release was significantly elevated during periarterial nerve stimulation only in young SHR. Thus, these results suggest that a parallel enhancement of norepinephrine release in hypothalamus with that of peripheral nervous system may play an important role during development of hypertension in young SHR. PMID- 2921080 TI - Endothelium-mediated spontaneous response in aortic rings of deoxycorticosterone acetate-hypertensive rats. AB - Aortic rings isolated from normotensive Sprague-Dawley rats (CONT) exhibited spontaneous tone when the preparations were stretched. After administering deoxycorticosterone acetate (DOCA), the rats became hypertensive, and this spontaneous tone increased remarkably. The spontaneous tone was dependent on the extracellular calcium concentration. Incubation with the calcium entry blocker D 600 attenuated the spontaneous response to a greater degree in rings from DOCA rats than in rings from CONT rats. Nifedipine relaxed the already developed spontaneous tone. Removal of the endothelium greatly depressed spontaneous tone, but did not diminish the contraction caused by norepinephrine. On the basis of our findings, we conclude that 1) spontaneous tone depends on calcium influx, presumably through specific stretch-operated membrane channels, 2) these stretch dependent channels are blocked by D-600 and nifedipine, 3) spontaneous tone is enhanced in DOCA hypertension, and 4) the endothelium appears to act as a receptor for stretch, mediating--at least in part--the spontaneous contractile response by releasing a constrictor agent. PMID- 2921081 TI - Chronic hypotensive effects of verapamil in angiotensin hypertension are steroid independent. AB - This study was designed to examine the mechanisms that contribute to the chronic hypotensive effects of verapamil during angiotensin II-induced hypertension. Hypertension was induced in five dogs by continuous intravenous infusion of angiotensin II (5 ng/kg/min) for 17 days. On the sixth day of angiotensin II infusion when daily sodium balance was achieved, mean arterial pressure (control, 92 +/- 4 mm Hg), plasma aldosterone concentration (control, 5.2 +/- 0.9 ng/dl), and renal resistance (control, 0.28 +/- 0.01 mm Hg/ml/min) were increased 37 +/- 8 mm Hg, 13.6 +/- 5.0 ng/dl, and 0.20 +/- 0.05 mm Hg/ml/min, respectively. At this time there were no significant changes in glomerular filtration rate, effective renal plasma flow, net sodium and water balance, or extracellular fluid volume. Subsequently, when verapamil was infused (at 2 micrograms/kg/min) simultaneously with angiotensin II (days 7-13), there was a net loss of 55 +/- 10 meq sodium, a 7.0 +/- 0.7% fall in extracellular fluid volume, and approximately a 70% reduction in the chronic effects of angiotensin II on mean arterial pressure and renal resistance; in contrast, verapamil failed to attenuate the long-term aldosterone response to angiotensin II. Further, although glomerular filtration rate and effective renal plasma flow tended to increase during verapamil administration, there were no consistent chronic long-term changes in these renal indexes. In comparison with these responses in hypertensive dogs, when verapamil was infused for 7 days before the induction of angiotensin II hypertension, there were no significant changes in any measurements except mean arterial pressure, which fell 11 +/- 1 mm Hg. Thus, these data fail to support the hypothesis that the chronic stimulatory actions of angiotensin II on aldosterone secretion are dependent on a sustained increase in transmembranal calcium influx. Moreover, these data indicate that the pronounced long-term hypotensive effects of verapamil in angiotensin II hypertension are due to impairment of the direct renal actions of angiotensin II rather than the indirect sodium-retaining effects that are mediated via aldosterone secretion. PMID- 2921082 TI - Effect of irradiation, cyclophosphamide, and etoposide (VP-16) on number of peripheral blood and peritoneal leukocytes in mice under normal conditions and during acute inflammatory reaction. AB - In order to develop a suitable model for studying the role of granulocytes and monocytes in resistance against pathogenic microorganisms, we investigated the effect of irradiation and cytostatic treatment (cyclophosphamide and VP-16) on the number of both peripheral blood and peritoneal leukocytes in male Swiss mice. Irradiation and cyclophosphamide treatment severely decreased the number of both granulocytes and monocytes in peripheral blood, whereas VP-16 only lowered the number of blood monocytes to a significant degree and had little effect on the number of blood granulocytes or lymphocytes. When normal mice were injected intraperitoneally with newborn calf serum (NBCS) the number of peritoneal granulocytes rose about 100-fold within 6 h. In irradiated and cyclophosphamide treated mice, this influx of granulocytes into the peritoneal cavity was virtually eliminated, as was the concomitant increase in the number of blood granulocytes; in VP-16-treated mice, on the other hand, the number of peripheral blood and peritoneal granulocytes increased to the same degree as in normal mice. An increase in the number of peripheral blood monocytes and peritoneal macrophages occurred 24-48 h after injection of NBCS in normal mice. This increase was significantly impaired by irradiation as well as by treatment with cyclophosphamide or VP-16. PMID- 2921083 TI - Effects of psoriatic scale extracts on oxidative metabolic responses in granulocytes assessed by chemiluminescence. AB - The peptide fractions containing C5a des arg and anionic neutrophil activating peptide (ANAP) and the low-molecular-weight fractions containing LTB4 in psoriatic scale extracts exert a potent polymorphonuclear leukocyte (PMN) chemotactic activity. To evaluate whether any of these components in the psoriatic scale extracts stimulate a respiratory burst in PMNs, we studied luminol-dependent chemiluminescence (CL) in PMNs under their direct stimulation. After fractionation by molecular sieve chromatography, pooled peptide fractions eluting near the cytochrome c marker from eight samples induced high CL in PMNs, whereas those eluted in low-molecular-weight fractions after vitamin B12 marker were very weak in this response. Moreover, in six samples such low-molecular weight fractions eluting near the vitamin B12 marker were found to have a suppressive effect on the oxidative metabolism of neutrophils induced by other stimulators. These findings suggest that the fraction of chemotactic peptides in psoriatic scales plays a major role in the activation of PMNs, inducing tissue damage in the psoriatic lesional epidermis. On the other hand, at least some low molecular-weight components in psoriatic scales seem to exert an inhibitory effect on the respiratory burst induced by other activators. PMID- 2921085 TI - How efficient is "safer sex" in preventing HIV infection? PMID- 2921084 TI - Aggregated human colostral sIgA stimulates delayed, non-complement-dependent, NBT reduction by human neutrophils. AB - Antibodies often alert polymorphonuclear neutrophils (PMNs) to the presence of pathogens. In a study to learn if secretory immunoglobulins can carry out this function, we observed that as little as 4 micrograms/ml of secreted human immunoglobulin A from colostrum (sIgA), in the absence of antigen, stimulated human PMNs to reduce nitroblue tetrazolium (NBT). NBT reduction was inhibited 71% by superoxide dismutase. Active complement pathways were not required since comparable activity was obtained in the presence of heat-inactivated serum. Aggregated forms of sIgA were much more stimulatory than nonaggregated dimeric sIgA. Such interaction between PMNs and sIgA could act in situ to enhance protection against infections of exposed body sites or could initiate inflammatory tissue damage. PMID- 2921087 TI - The microbiological efficacy of the combination of fosfomycin and vancomycin against clinically relevant staphylococci. AB - Infections with multiresistant strains of Staphylococcus aureus and Staphylococcus epidermidis pose severe clinical problems. The drug of choice in such cases, vancomycin, is potentially ototoxic and nephrotoxic and this may give rise to additional problems in the patient. Fosfomycin has been shown to be nephroprotective when given with vancomycin and with other nephrotoxic drugs. We report the inhibitory and bactericidal activity of fosfomycin and vancomycin alone and in combination against 26 clinically relevant strains of S. aureus and 48 strains of S. epidermidis. In most instances these two drugs showed indifferent or additive effects, synergism or antagonism was only rarely observed. Assessment of the bactericidal action of the combination revealed similar effects. The combination of fosfomycin and vancomycin may, therefore, be beneficial in clinical situations where the nephrotoxic effect of vancomycin cannot be tolerated. PMID- 2921086 TI - The penetration of antibiotics into human pancreas. AB - In order to analyse the penetration of two antibiotics (mezlocillin and metronidazole) which cover the spectrum of microorganisms involved in pancreatic infection, we determined their concentration in pancreatic tissue, juice and cyst fluid in 16 patients undergoing pancreatic surgery. In addition, the external pancreatic fistula fluid of one patient was analysed for antibiotic concentration and bacterial counts during a seven-day treatment with mezlocillin, metronidazole and netilmicin (i.v.). Antibiotic concentrations were determined by HPLC between 16 and 210 (median 74) min after i.v. administration of 4 g mezlocillin and 500 mg metronidazole, respectively. The median concentration of mezlocillin was 23.2 (range: 3.1-37.4) mg/kg, 15.9 (range: 4.2-55.0) mg/l and 9.9 (range: 5.2-14.8) mg/l in pancreatic tissue, juice and cyst fluid, respectively. The median concentration of metronidazole was 5.1 (range: 1.8-13.0) mg/kg, 8.5 (range: 3.6 16.2) mg/l and 1.2 (0.9-1.4) mg/l in pancreatic tissue, juice and cyst fluid, respectively. From the fistula patient, seven different bacteria were cultured (five aerobic and two anaerobic isolates); their concentration in fistula fluid ranged from 10(5) to 10(7) CFU/ml. The bacteria sensitive for mezlocillin and metronidazole disappeared after four days of i.v. treatment, whereas the two isolates sensitive for netilmicin showed continuous growth seven days after i.v. treatment. The peak concentrations for mezlocillin, metronidazole and netilmicin in the fistula fluid were 6.8 mg/l, 5.6 mg/l and less than 0.1 mg/l, respectively. PMID- 2921089 TI - Treatment of pertussis with josamycin. PMID- 2921088 TI - Epidemiology of HIV and hepatitis B virus (HBV) in selected African and Asian populations. AB - 401 sera from patients of a rural hospital in Zimbabwe (1987), 211 South African sera (1982/83), as well as 460 sera from four Katmandu hospitals (1985) were tested for HIV-1 antibodies. The sera from Zimbabwe and Nepal were additionally tested for anti-HIV-2 using a panel of different tests, for hepatitis B markers, and partially for antibodies against other viral, bacterial, and protozoal antigens. Detailed clinical and sociodemographic data were taken from the Zimbabwe and Katmandu patients. The prevalence of HIV-1 antibodies in the Zimbabwe study population was 3.2%. All infections were found in the age group 17 to 30 years (n = 254). The epidemiological situation was entirely different from that of HBV (hepatitis B virus). No serum could be confirmed to be anti-HIV-2 positive, but a definite diagnosis is still difficult to establish. Regular town contacts may be considered a possible risk factor. Antibodies against HIV-1 could not be detected in the South African and Asian sera. The seropositivity for anti HBc in Katmandu (14%) and the prevalence of HBsAg (1.1%) was much lower than reported from other Asian countries. PMID- 2921090 TI - Tobramycin dosage recommendation in patients with cystic fibrosis. PMID- 2921091 TI - Unusual resistance to cefuroxime by strains of Alcaligenes faecalis. PMID- 2921092 TI - Surveillance of hospital-associated infections. AB - A totally laboratory-based system for surveillance of hospital-associated infections is not sensitive enough, but may be a base for surveillance of urinary tract infections. The SENIC study has convincingly demonstrated that for the four most important hospital-associated infections in the U.S., active ongoing intense surveillance based on daily patient chart and/or Kardex reviews in itself reduces the infection rate. Studies in other countries indicate that for postoperative wound infections this holds true also outside the U.S. For other types of nosocomial infections, similar studies outside the U.S. are urgently needed. The SENIC study underlines the importance of infection control nurses, but also of well-trained hospital epidemiologists. PMID- 2921093 TI - WHO symposium: Use and abuse of antibiotics worldwide. Sept. 29-30, 1988, Freiburg, FRG. Summary reports. PMID- 2921094 TI - Human leptospirosis--a review of 50 cases. AB - Epidemiological and clinical aspects of 50 consecutive patients, 47 adults and three children, hospitalized between 1977 and 1987 for human leptospirosis, were reviewed. 45 (90%) of the patients were from rural regions. 32 (64%) cases occurred in individuals at occupational risk for the infection. 35 (70%) cases were registered in the warm season. The source of infection was known in 34 (68%) cases. Weil's disease was diagnosed in 31 (62%) patients, aseptic meningitis in 12 (24%) and acute unexplained fever in seven (14%). Haemodialysis was required for 11 (35%) patients with Weil's disease. Three (6%) patients died. Cause of death was massive gastrointestinal haemorrhage in two and renal failure in one. Leptospira icterohaemorrhagiae was responsible for 39 (78%) cases, Leptospira canicola for six (12%), Leptospira grippotyphosa for two (4%), and Leptospira australis, Leptospira ballum and Leptospira sejroe, for one case each. A muscle biopsy was performed in six patients and a renal biopsy in three. Focal necrotic muscular changes, with mild mononuclear infiltrate, were found. Pigmented casts in distal convoluted tubules, mild interstitial inflammatory infiltrate and mesangial enlargement of some glomeruli were observed in kidney biopsies. A good knowledge of the protean clinical manifestations of leptospirosis and an accurate laboratory study are required for a correct diagnosis. PMID- 2921095 TI - Spinal anesthesia. PMID- 2921096 TI - On the central effects of a new partial benzodiazepine agonist Ro 16-6028 in man: pharmaco-EEG and psychometric studies. AB - In a double-blind placebo-controlled study, the encephalotropic and psychotropic properties of a new partial benzodiazepine agonist Ro 16-6028 were investigated as compared to a pure agonist diazepam utilizing quantitative EEG and psychometric analysis as well as clinical observations. Ten normal volunteers received randomized (latin square design) and at weekly intervals, single oral doses of placebo, 0.05 mg, 0.1 mg and 0.2 mg Ro 16-6028 and 10 mg diazepam as reference substance. EEG-recordings, psychometric tests and evaluation of blood pressure, pulse and side effects were carried out at 0, 1, 2, 3, 4 and 6 h. Computer-assisted spectral analysis of the EEG demonstrated after 10 mg diazepam, a typical "anxiolytic" pharmaco-EEG profile characterized by an increase of beta activity, decrease of alpha activity and acceleration of the centroid total activity. Ro 16-6028 induced in the vigilance-controlled recordings a similar profile thereby exhibiting tranquilizing properties too. However, in the resting condition we observed also an increase of delta/theta activity along with a decrease of alpha activity while the beta augmentation was observed mostly in the fast frequency bands and not so much in the middle fast frequency bands as is the case with the known full agonists. The latter findings were somewhat reminiscent of the pharmaco-EEG profiles seen often in certain neuroleptics. Our data indicate a selective sedation after the novel partial agonist. Dose/treatment efficacy calculations demonstrated 10 mg diazepam as the most CNS-effective drug followed closely by 0.2 mg Ro 16-6028, 0.1 mg and 0.05 mg, while placebo induced the least changes. Only 0.2 mg Ro 16-6028 and the reference compound differed from placebo at all times. Time-efficacy calculations showed a peak effect of the novel partial agonist around the 3rd h and that of diazepam in the 1st h. Psychometric tests demonstrated similar findings. After 0.2 mg Ro 16-6028 a decrease of attention, numerical memory, psychomotor activity, wakefulness and CFF was observed, while mood improved at later time periods outlasting the sedation. After 10 mg diazepam 10 out of 13 psychometric and psychophysiological variables showed significant findings previously described as typical for anxiolytic sedatives in normals. On the whole, the partial agonist induced less sedation than the full agonist, which is reflected in its superiority in regard to noopsychic and thymopsychic functions. Evaluation of pulse and blood pressure showed no clinically relevant findings. The new partial agonist was well tolerated. PMID- 2921097 TI - 99mTc hexakis-t-butyl isonitrile (TBI): an agent for the diagnosis of coronary artery diseases. AB - Basic and clinical studies were undertaken to determine pharmacokinetic mechanisms, blood flow-related characteristics and potential clinical utility of the 99mTc hexakis-t-butyl isonitrile (TBI) in the non-invasive diagnosis of ischemic heart diseases. Pharmacokinetic studies with TBI in animals demonstrated a high initial lung, heart and liver uptake. The lung clears at a relatively faster rate, the activity in the heart remained constant with a buildup of activity in the liver. These pharmacokinetic characteristics allowed for a myocardial imaging at 30-45 min post-injection at rest. The regional myocardial distribution of TBI was shown to be linearly related to microsphere-determined regional myocardial blood flow with a redistribution potential in transient ischemic myocardium (i.e., mimics 201Tl). The first pass extraction fraction (in vitro) for TBI was shown to be nearly 100% and independent on flow levels. In general, the slow tissue clearance rate or the lack of it might be due to the high degree of lipophilicity with the complete lack of any hepatic or extrahepatic metabolism to a less lipophilic metabolite. The complex demonstrated a high degree of cardiac membrane association. The net extraction in isolated heart slices was shown to be dependent on pH and temperature, independent of energy. The clinical studies demonstrated a similar pharmacokinetic pattern to the animal studies and documented the perfusion and ventricular function utility of TBI in the diagnosis of ischemic heart diseases. PMID- 2921098 TI - Simvastatin (MK 733) in heterozygous familial hypercholesterolemia: a two-year trial. AB - Simvastatin (MK 733), a new competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, given in daily doses of 20 mg and 40 mg for 104 weeks, has been shown to lower the serum total cholesterol and low density lipoprotein cholesterol level by more than 30% and the serum apoprotein B level by 20% in 19 adult patients with heterozygous familial hypercholesterolemia. A slight but non significant increase of high density lipoprotein cholesterol levels was shown throughout the trial with significant elevation of the serum apoproteins AI and AII only observed at week 52. Mild and transient clinical or biochemical (increases of creatine phosphokinase and transaminases) side effects, observed in some patients, did not necessitate the withdrawal of the medication. Full ophthalmological examinations did not reveal ocular disturbances, particularly no apparent increase of lens opacities, during the trial. Simvastatin seems to be an effective and safe drug as monotherapy in the treatment of heterozygous familial hypercholesterolemia. PMID- 2921099 TI - Cefoperazone pharmacokinetics in patients with liver cirrhosis: a predictive value of the ujoviridin test. AB - Pharmacokinetics of cefoperazone was studied in 10 healthy volunteers and in 11 patients with liver cirrhosis. In the same persons, we also examined the clearance of ujoviridin--a preparation of indocyanine green. Within 12 h, 31.8 (+/- 7.6)% of the 2 g dose of cefoperazone was eliminated in the urine of healthy persons and 74.3 (+/- 7.9)% (mean +/- SD) was eliminated in the urine of cirrhotics. The biological half-life (beta-phase) of cefoperazone in healthy volunteers and in cirrhotics was 1.77 (+/- 0.25) and 4.29 (+/- 1.16) h, total clearance 1.009 (+/- 0.187) and 0.583 (+/- 0.169) ml/s and hepatic clearance 0.694 (+/- 0.174) and 0.152 (+/- 0.079) ml/s, respectively. The differences are statistically significant (p less than 0.001). We also found good correlation between total clearance of cefoperazone and clearance of ujoviridin (r = 0.842) and even better between hepatic clearance of cefoperazone and ujoviridin clearance (r = 0.957), both statistically significant. The findings suggest that the dosage of cefoperazone should be reduced in patients with liver cirrhosis and that the ujoviridin clearance test is a good indicator of impaired cefoperazone elimination. PMID- 2921100 TI - Efficacy of atenolol in the short and long-term treatment of patients with effort stable angina. AB - A double-blind, crossover, randomized placebo controlled study involving 15 patients with effort stable angina, was carried out to assess atenolol (A) 100 mg during an 8-week period. Thereafter, atenolol antianginal efficacy was evaluated in a 6-month follow-up open non-comparative study. No antianginal drugs other than A were administered except for isosorbide dinitrate 5 mg when necessary. At the end of the 2-week wash-out period, and at the end of each 2-week period during the crossover phase of the study, and every 12 weeks during the 6-month follow-up, an ergometric test was performed and the following parameters were evaluated: HR, SBP, DP, Total Work Load (TWL) and S-T changes. The Barlett's test was performed to assess variance homogeneity, while the Tukey Hd test was used to evaluate the parameters during the treatments. During atenolol, the reduction in SBP was close to statistical significance, HR and S-T were significantly reduced (p less than or equal to 0.05) whereas TWL was significantly increased (p less than or equal to 0.05). During long-term atenolol treatment, all cardiovascular parameters clearly improved in comparison to the placebo period, confirming the antianginal efficacy of atenolol, even in the long-term treatment. PMID- 2921101 TI - Lowering of maximum urethral pressure by (D-Met2, Pro5)-enkephalinamide in patients with neurogenic vesicourethral dysfunction due to spinal cord injury. AB - The effect of (D-Met2, Pro5)-enkephalinamide upon urethra in patients with chronic neurogenic vesicourethral dysfunction due to spinal cord injury was investigated. Urethral pressure profile was recorded with Urolab 1154 and 1700A urethral pressure profile puller-pump. Ten mg of the drug was administered subcutaneously. Urethral pressure profile was again recorded at 10, 20, 30, 40, 50 and 60 min after drug administration. Heart rate was also noted at these time points. There was a significant decrease in maximum urethral pressure from 134 +/ 19 cm H2O in the basal study to 107 +/- 28 cm H2O at 10 min (p less than 0.01); 102 +/- 30 cm H2O at 20 min (p less than 0.001); 94 +/- 19 cm H2O at 30 min (p less than 0.001); 100 +/- 20 cm H2O at 40 min (p less than 0.001); 102 +/- 29 cm H2O at 50 min (p less than 0.001); and 109 +/- 36 cm H2O at 60 min (p less than 0.001) after subcutaneous administration of (D-Met2, Pro5)-enkephalinamide. There was a significant increase in heart rate from 81 +/- 5 to 95 +/- 9 at 10 min (p less than 0.01) and to 87 +/- 10 at 20 min (p less than 0.01) after the drug. Subsequenly, the heart rate returned to near-basal values. The side effects were: conjunctival injection in all the cases; dryness of mouth in two; itching over the body in one; sensation of insect crawling over the body in one; and feeling of oppression over the chest immediately after drug administration in one.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2921102 TI - Lawmaking and lobbying: two viewpoints. PMID- 2921103 TI - Prehospital pain control: nitrous oxide inhalation. AB - Pain control in the prehospital emergency setting is often a neglected aspect of patient care. This article reports findings from 6 months of nitrous oxide use in the field. Its safety and effectiveness in selected cases is demonstrated. PMID- 2921104 TI - Toxic shock syndrome reporting in Iowa. AB - Since August 1980 131 cases of TSS-like illness have been reported by health professionals in Iowa to the Department of Public Health. Over half of the cases have been reported by the Statewide Epidemiology and Consultation Program. PMID- 2921105 TI - The case of a young man with a stroke. PMID- 2921106 TI - A pain in the gluteus. PMID- 2921107 TI - The emerging personnel shortage. PMID- 2921108 TI - Ethical dilemmas in head and neck cancer. AB - Ethical dilemmas in head and neck cancer daily confront physicians, patients, families, and society at large. For every situation there are potential benefits and real burdens, as well as risks. There are no "right" answers for any given situation, but there are processes for assisting the primary decision makers involved in reaching meaningful and appropriate decisions. This paper asks some pertinent ethical questions and suggests some ways of responding to the issues. PMID- 2921109 TI - Role of aerobic gram-negative rods, anaerobes, and fungi in wound infection after head and neck surgery: implications for antibiotic prophylaxis. AB - The prevention of wound infection after major contaminated head and neck surgery is a critical issue for the head and neck surgeon. The proper interpretation of cultures taken from wounds is uncertain. Multiple organisms are invariably isolated from this nonsterile site including indigenous aerobic and anaerobic flora, aerobic gram-negative rods, and fungi. We present evidence from controlled antibiotic trials that demonstrate the pathogenicity of oropharyngeal anaerobic flora. The presence of aerobic gram-negative rods and fungi generally represent colonization and antibiotic coverage need not routinely be directed at these organisms. On the other hand, the antibacterial spectrum of an agent used for head and neck would prophylaxis should include coverage for pathogenic oral flora, namely the gram-positive aerobic cocci (especially streptococci) and anaerobic bacteria. PMID- 2921110 TI - Needle aspiration biopsy of the pre-epiglottic space. AB - Clinical staging of supraglottic carcinoma requires evaluation of the pre epiglottic space (PES). To explore the role of fine needle aspiration biopsy of the PES in the staging of epiglottic carcinoma, endoscopic transvallecular fine needle aspiration biopsies of the PES were performed in 16 patients with epiglottic carcinoma. The results of aspiration cytology were compared with CT scanning and postoperative histopathologic sections of the PES after total or supraglottic laryngectomy. This preliminary report shows that needle aspiration biopsy of the PES is a safe and sensitive technique, having a high correlation with histopathologic follow-up. Needle biopsy, along with CT scan, is clinically useful in staging the PES, which cannot be examined directly. PMID- 2921111 TI - Bulbar amyotrophic lateral sclerosis: patterns of progression and clinical management. AB - Patients with bulbar amyotrophic lateral sclerosis (ALS) are often referred to the otolaryngologist/head and neck surgeon and speech pathologist for evaluation and management of dysphagia and dysarthria. These patients comprise an unusual group because of the progressive and multi-system nature of their illness. The neuromuscular disabilities associated with bulbar ALS cause a myriad of related symptoms associated with swallowing, speech, and respiration. Although the rate of progression cannot be predicted, a general pattern of progression is noted. Bulbar disease accounts for the majority of the worst symptoms of ALS. The loss of the ability to swallow changes eating from a pleasurable task to a burden of survival. Loss of communication effectively imprisons the patient in a state of isolation. The progressive weakness of respiration, predominantly a spinal rather than bulbar manifestation, is the cause of death for nearly all ALS patients and is also discussed. The general patterns of progression of bulbar ALS are outlined in this paper. The development of symptoms are correlated with specific treatment recommendations to aid the clinician in devising an orderly plan of management for this progressive disease. PMID- 2921112 TI - Modern management of cervical scrofula. AB - From 1970 to 1984, 32 patients were treated for tuberculous (TB) masses, which measured 1.2-5.5 cm. The posterior triangle was involved in 19 patients, anterior triangle in 7, and more than one triangle in 6 (3 bilateral). A superficial node was excised for diagnosis. Acid-fast bacilli were identified on the smear of 18 patients. Caseation necrosis was present in 27 specimens, sarcoidosis in four, nonspecific lymphadenitis in one; all cultures grew Mycobacterium tuberculosis. A chest x-ray showed no active TB. Chemotherapy was given for 9-18 months (9 months when only one node was diseased and 18 months with extensive nodal involvement). Follow-up examinations in all patients (greater than 3 years, mean 8.6 years) has revealed no recurrence. The need to excise all cervical TB nodes, chronically inflamed and often fused to important structures, was eliminated by adequate chemotherapy. PMID- 2921113 TI - Rationale for elective modified neck dissection: a word of caution. PMID- 2921114 TI - [Specific IgE to Staphylococcus aureus in patients with atopic dermatitis]. AB - It is a well-known feature of atopic dermatitis (AD) that the patient's skin is heavily colonized by Staphylococcus aureus. S. aureus-derived antigens may be important triggers of the immune response and may significantly contribute to the genesis of the cutaneous pathology of AD. Therefore, serum samples of 52 patients with AD, all of whom had signs of moderate to severe disease activity, were tested for antistaphylococcal IgE antibodies with RAST discs coupled to antigens derived from Wood 46 strain. Total IgE concentrations and specific IgE to nine different common allergens were also determined. Only 2 patients showed significant levels of specific IgE antibodies to S. aureus (RAST class greater than or equal to 2). Both these patients were found to have high total IgE and significant levels of specific IgE to all nine common allergens tested. One of the patients had marked eosinophilia. We conclude that the presence of specific IgE to S. aureus is not correlated with the disease activity in AD. Specific antistaphylococcal IgE does not represent an important diagnostic feature in AD, but may be of importance for the detection of subgroups within patients affected by AD. PMID- 2921115 TI - [Regression of over 150 skin metastases of malignant melanoma with complex homeopathic therapy]. AB - Within a period of 7 years, a female patient with malignant melanoma on the calf developed over 150 cutaneous metastases in the vicinity of the primary tumour. During the course of the following 8 years all but one of these disappeared again. One year later the patient died of metastases in the lungs and brain. The author discusses this unusual history and examines the significance of a course of homeopathic "complex therapy" administered during the decisive period. PMID- 2921116 TI - [Lichen ruber ulcerosus plantae]. AB - A 66-year-old patient suffering from painful ulcerative lichen planus of the feet is presented. Various treatments (topical and oral corticosteroids, irradiation and a 6-month therapy with acitretin) were tried without success. Skin grafting in the affected areas was helpful and resulted with an acceptable and painless state. PMID- 2921118 TI - AIDS and osteopathic medical education. PMID- 2921117 TI - Screening for breast health. PMID- 2921119 TI - Refining our cholesterol awareness. PMID- 2921120 TI - Comparison of three methods of determining oxygen consumption and resting energy expenditure. AB - Resting energy expenditure (REE) in intensive care unit patients was evaluated by three methods--indirect calorimetry (REE-IC), Fick equation (REE-F), and estimation from the Harris-Benedict equation (REE-HB). The mean REE-IC and REE-F values did not differ significantly. However, both values were significantly higher than the REE-HB. The present study indicates that a reasonably accurate estimate of the REE can be obtained from data available by Swan-Ganz catheterization. The Fick method is technically simpler to perform and less expensive than indirect calorimetry. The invasive nature of Swan-Ganz catheterization is a major disadvantage. However, right-sided heart catheterization frequently is required for the management of intensive care unit patients. For them, REE-F appears to be a reasonable alternative. PMID- 2921121 TI - Use of hyaluronate sodium v air in extracapsular cataract extraction. AB - A total of 17 patients underwent extracapsular cataract extraction with artificial lens implantation by one surgeon. Eight were given hyaluronate sodium (Healon) during the procedure, while nine received only air. Corneal thickness and endothelial cell counts were obtained one day prior to surgery and 90 days postoperatively. There were mean cell losses of 10.5% and 11.2% in the Healon and air groups, respectively. This is a mean difference of 0.7%, which is not significant statistically. Therefore, despite several studies that demonstrate the protective value of hyaluronate sodium on the corneal endothelium during anterior segment surgery, this study showed no such difference in the protective effects between the two. PMID- 2921122 TI - Biomechanical and osteopathic approach to shoulder pain. AB - One of the most common complaints heard by primary care physicians is shoulder pain. Yet, most shoulder discomfort can be attributed to a variety of physiologic and anatomic dysfunctions outside of the glenohumeral joint. This paper addresses the anatomic and biomechanical mechanisms of shoulder motion and presents a logical approach to diagnosis and osteopathic treatment of the sore shoulder. PMID- 2921123 TI - Phlegmasia cerulea dolens as a complication of percutaneous insertion of a vena caval filter. AB - Unsuccessfully treated iliofemoral venous thrombosis can result in pulmonary embolism, phlegmasia cerulea dolens, and post-thrombotic syndrome. Phlegmasia cerulea dolens is characterized by tense swelling of the lower extremity with tenderness of the thigh over the femoral vein, mottling of the limb, and absent distal pulses. Without treatment, phlegmasia cerulea dolens can progress to cause venous gangrene and ultimate limb loss. In the reported case, phlegmasia cerulea dolens developed in a middle-aged woman with metastatic thyroid carcinoma following Greenfield filter placement via the femoral vein after heparinization for deep-vein thrombophlebitis had failed. PMID- 2921124 TI - Acute visual loss in systemic lupus erythematosus. AB - Systemic lupus erythematosus (SLE) often presents as a multisystem disease that can be difficult to diagnose. Although ocular symptoms are infrequent, actual acute visual loss has been reported. A review of four cases of acute visual loss from a lupus clinic revealed that two patients had visual loss as a presenting sign of SLE. One had bilateral occipital lobe infarctions, the other multiple cotton wool spots and an attenuated retinal vascular system. Of the two patients with documented SLE prior to the onset of visual problems, one presented with a coincidental retinal tear and the other with retinal phlebitis. PMID- 2921125 TI - Urinary tract endometriosis. AB - Although endometriosis is a common gynecologic pathologic phenomenon, involvement of the urinary tract is relatively rare. The clinical presentation and course of urinary system disease is extremely variable, as illustrated by the seven cases presented in this report. Therapy primarily is surgical, but a thorough understanding of the disease process and a complete knowledge of the patient's history and desires for fertility conservation are necessary to plot the most appropriate treatment course. Bladder involvement is more common, and usually less devastating, than either ureteral or kidney involvement. No signs, symptoms, or physical findings are pathognomonic, and the clinician must maintain a high index of suspicion in all cases of advanced pelvic endometriosis. PMID- 2921127 TI - The Shanghai International Conference in Radiation Oncology (SICRO). Shanghai, China, May 1987. Selected presentations. PMID- 2921126 TI - Preparing an AIDS policy for colleges of osteopathic medicine. AB - There are currently 1.5 million people in the United States infected with the human immunodeficiency virus. In the next five to ten years, this nation's health care facilities and medical schools could be inundated with staggering numbers of the sick and dying. Unless our osteopathic and allopathic colleges and allied health care centers are adequately prepared for this crisis, many of these people will not receive adequate care. A recent survey conducted by Ohio University College of Osteopathic Medicine (OU-COM) revealed that many osteopathic colleges do not have a formal policy to deal with the multiple complex issues of the AIDS epidemic. This brief article reviews the approach which OU-COM took to correct this deficiency. In addition, the article includes OU-COM's conclusions and recommendations regarding many of the salient issues, with a discussion of the rationale behind those conclusions. PMID- 2921128 TI - Radiotherapy in China today. AB - The treatment of cancer by radiation in China began in the early 1930's. However, up to 1949, its development was very slow. Following Liberation, the growth of this specialty has been extremely rapid, as shown by the kind of modern radiotherapeutic equipment that is available today in many centers of our country. Currently almost every province has a cancer center with a good radiotherapy department and consequently, treatment results have improved over the past years. Due to the large number of patients seen in every radiotherapy department, many types of cancers are treated each day; thus clinical trials can be concluded in a shorter time. The author will show the kind of work that is being achieved in China in general, and Shanghai in particular. PMID- 2921129 TI - Radiation therapy of nasopharyngeal carcinoma: prognostic factors based on a 10 year follow-up of 1302 patients. AB - One thousand three hundred and two patients with carcinoma of the nasopharynx were initially treated with radiation therapy at this hospital in 1974. The overall 1-, 3-, 5-, and 10-year survival rates were 89.86%, 60.60%, 47%, and 33.03% respectively. At the end of the radiotherapeutic course the residual lesion rate was 10.52% in the nasopharynx 17.27% in cervical lymphnode. In about one-half of the cases with residual lesions, the masses disappeared without further treatment. Prognosis was not improved in the group with supplemental doses. The recurrence rates of the primary nasopharyngeal and metastatic cervical lesion were 18.43%, and 16.12% respectively within 10 years after initial treatment. The 10-year survival rate of the patients with a second course of radiotherapy was 15.04%, higher than of those not retreated (4.9%). Data of this group also reveal that the present pathological classification cannot reflect the degree of prognosis. Increase dosage or combination with chemotherapy did not improve the prognosis. Radiation encephalomyetic damage is discussed. PMID- 2921130 TI - Comparison of continuous and split-course radiotherapy for nasopharyngeal carcinoma. AB - From July 1977 through December 1980, a series of 1882 cases with nasopharyngeal carcinoma (NPC) had their first definitive radiotherapy course at our department, 1424 cases by continuous treatment regimen, and 458 cases by a split-course regimen. The interval of the split was 11-45 days, with an average of 28.6 days. Trials were non-randomized, but the treatment conditions for both groups were the same. The overall 5-year survival rate was 34.6%, 35.4% for the continuous group and 31.8% for the split-course group. The 5-year survival rate for Stage IV patients (squamous cell carcinoma Grade III) was 25.7% (69/268) for the continuous group and 14.1% (10/71) for the split-course group. Breaking down the cases by primary and cervical metastatic sites, for T3 cases, the 5-year local control rate for the primary site was 29.4% (133/451) for the continuous group, and 18.6% (22/118) for the split-course group. These differences are statistically significant (p less than 0.05). However, according to the data shown by this series, we can conclude that the split-course treatment regimen had no benefit over the continuous one when overall 5-year survival is considered. PMID- 2921131 TI - Long-term observation after radiotherapy for nasopharyngeal carcinoma (NPC). AB - One thousand one hundred twenty-seven cases of nasopharyngeal carcinoma were treated with routine radiotherapy from October 1969 to March 1976, of which 436 cases have survived for more than 5 years, 323 cases have survived for over 10 years. The follow-up rate was 98.4%. The present paper analyzes the factors involved in these 436 cases. All patients were treated with tele60Co unit, and in the neck some cases were treated with orthovoltage therapy. The total dose to the primary lesion was 60-75 Gy in 6-8 weeks and in a few cases over 80 Gy were needed, and 50 Gy were applied bilateral cervical lymphatic chain. In this series of cases the 10-year overall survival rate was 28.7%, with Stage I being 66.7%, Stage II 46.5%, Stage III 28.0%, and Stage IV 18.6%, respectively. Statistically, 68 cases died of cardiovascular and other diseases and should be eliminated for net survival calculations. Therefore, we could obtain an actual 10-year survival rate of 30.5%. However, it should be noted that most of these cases were advanced, with Stage III, IV accounting for 82.3%, thus at Stage I, II the 10 year survival rate was 48%, while at Stage III, IV rate was down to 24.5%, which was statistically significant (p less than 0.01). Local and cervical recurrence as well as distant spread of diseases, for these cases started from the fifth to the tenth year after radiotherapy, the mortality caused by the above-mentioned three sites together was 76.9%. According to these findings, we propose that follow-up after radiotherapy in NPC exceeds 10-years. Of the 323 NPC cases, 10 were nasopharyngeal local recurrence which were re-irradiated, accounting for 3.1%. This paper shows that the 3-year survival rate in the local recurrence which were re-irradiated was 34.5%, the 5-year survival rate was 14.8%, and the 10-year survival rate was 11.5%. The failure after re-irradiation was caused by local recurrence and metastasis with a mortality of 83.6%. These results emphasize that the success of initial irradiation is important. PMID- 2921132 TI - Intracavitary radiation treatment of nasopharyngeal carcinoma by the high dose rate afterloading technique. AB - Sixty-four patients with nasopharyngeal carcinoma were treated by various combinations of external irradiation with intracavitary radiotherapy using the high dose rate afterloading technique. The afterloading intracavitary radiation (AIR) was given as a routine boost or for residual or recurrent disease. The external irradiation dose varied from 45 to 70 Gy, whereas the AIR dose ranged from 10-50 Gy, depending on the nature of the primary nasopharyngeal lesion. The results were quite encouraging, although the longest follow-up so far has only been just over 4 years. Of 13 such cases that received external radiotherapy plus AIR as primary treatment, 12 have survived. However, of the 9 cases who received AIR for local recurrence after external radiotherapy, only 5 survived. Of the total of 64 cases treated by AIR from June 1981 to May 1986, 54 are alive. No serious radiation sequelae have been observed. It can be concluded that AIR for nasopharyngeal carcinoma is indicated for boosting the dose to the nasopharyngeal cavity with appropriate reduction in external irradiation dose, and for residual or recurrent disease after primary external radiotherapy. PMID- 2921133 TI - Ten-year follow-up of esophageal cancer treated by radical radiation therapy: analysis of 869 patients. AB - The 10-year follow-up 869 patients with esophageal cancer treated by radiation is presented with emphasis on treatment methods, and results. The survival rates declined as the staging of the lesion advanced (p less than 0.01). The results improve with the shortening of the lesion (p less than 0.005) in the absence of metastasis. The effect of radiation is closely related to the dose given. A booster dose of 5-10 Gy in addition to the conventional curative dose of 60-69 Gy may increase the long-term survival of this cancer. The causes of the external irradiation failure are mainly recurrence and out of control of disease. Also, the author has discussed the occurrence and prevention of some complications. PMID- 2921134 TI - High dose-rate afterloading in the treatment of cervical cancer of the uterus. AB - From January 1981 to December 1983, 380 patients with cervical carcinoma of uterus were treated with high dose-rate intracavitary afterloading therapy (Ralstron-20B) and 60Co external irradiation. All of these cases have been followed over 3-5 years. The 5-year survival rates for Stages I, II, III, and IV were 100%, 81.5%, 73.9%, and 0% respectively. The over all 5-year survival rate was 79.1%. The results were comparable to that of conventional radium therapy in 1980 (5-year survival rate for radium group: Stage I 50%, Stage II 72.2%, Stage III 52.2%, Stage IV 0%). The moderate and severe rectal reactions in this series were 11.8% and 1.6% (radium group moderate 6.0%, severe 2.2%), which were higher than that of radium group. The incidence of bladder reaction was 7.1%. The problems of high dose-rate intracavitary therapy and the combination therapy with intracavitary and external irradiation are discussed in this paper. PMID- 2921135 TI - External cobalt 60 irradiation alone for stage IIB carcinoma of the uterine cervix. AB - From 1964 to 1980, 97 patients with Stage IIb carcinoma of cervix uteri were treated by external 60Co irradiation alone. Of these 97 patients, 94 (96.9%) had squamous cell carcinoma. The parametrial extension of the lesion almost reached the pelvic wall in 73.2% and vaginal extension reached to the upper half of vaginal in 24.7% of the patients. A tumor dose of 60 Gy was given to the whole pelvis by a four field technic (opposing parallel AP and lateral portals) in 6-8 weeks. A booster dose of 10 Gy was delivered to the cervix by a pair of reduced opposing parallel AP portals or a perineal portal in a week. The doses delivered were equivalent to the Time-Dose-Fractionation (TDF) value of 110-130 at the center of pelvis and 90-110 in the whole pelvis. The 5-year survival rate for all 97 patients was 56.7%. It was 59.8% when those who died of other diseases were excluded. The prognosis of patients without residual tumor on the cervix and/or vagina was better than that with residual tumor (p less than 0.01). Thirty-seven patients died of cancer (23 died of recurrence, 8 of distant metastases, 2 of both, and 4 were lost before the fifth year). Of these 37 patients, 97.3% died within 3 years after initial treatment. During the radiation treatment, reactions were moderate. Late complications included 19 (19.6%) with mild cystitis and 16 (16.5%) with mild proctitis, 2 (2.7%) developed recto-vaginal fistula. These results were slightly poorer than those using intracavitary and external irradiation or the combination of preoperative irradiation plus surgery. Yet, for patients with extensions nearing the pelvic wall or with contra-indications to surgery or intracavitary radiotherapy, external irradiation alone is still of value. PMID- 2921136 TI - DNA flow cytometric analysis of human nasopharyngeal carcinoma in nude mice. AB - The tissue from a patient with nasopharyngeal carcinoma has been transferred to nude mice (BALB/c), and has successfully been growing through twenty passages. The tumors in the nude mice and primary human tumor have been examined for the cellular DNA content by FCM and also conventional pathological examination, chromosome analysis, and EBV test. The tumor take rate varied markedly in different passages with a mean value of approximately 70%, and showing a tendency to increase. The tumor doubling time within 6-12 weeks after transplantation of six tumors in 18 and 20 passages were 14.8 and 9.3 days respectively. However, the tumor volume at 12 weeks varied significantly, ranging from 438 to 1998 mm3. By FCM, it has been found that the values of DNA index were about the same in both primary tumor and the tumors in nude mice. The distribution of various phase cells in cell cycle was also about the same in both. In conclusion, the application of FCM to examine the cellular DNA content of the tumor in nude mice is a rapid and sensitive method, useful in the investigation on the stability of biological characteristics of human NPC in nude mice and in further studies on the effects by various therapeutic methods. PMID- 2921137 TI - The use of Chinese herb medicine in experimental radiotherapy. AB - Extracts from a group of destagnative herbs, 764-1, and the effective chemical, 764-3, were tested by an in vitro experiment using a HeLa-S3 cell line. Under aerobic conditions, the shoulder of the cell survival curve diminished or disappeared according to the different doses of 764-1 used, but no change in slope was observed. In nitrogen, when the dose of 764-1 increased to 20 mg/ml (ID20), besides the disappearance of the shoulder, the slope of the curve also showed changes at lower doses (4-8 Gy); up to 10-25 Gy the curve became more flattened. 764-3 showed almost a similar effect by mainly affecting the shoulder of the survival curve. At low drug doses a SER as high as 1.87 might be obtained under hypoxic condition. At the same time 764-1 was used in testing the effect on radiation lung damage. It was found that 764-1 could markedly inhibit the change of alveolar surfactant at 1 and 3 weeks after radiation. A wide field of investigation is thus spread out in front of us on radiosensitization and protection. Further studies on 764-3 are carried out. PMID- 2921138 TI - Establishment, characteristics, and utilization of a new in vivo-in vitro system. AB - Radiotherapy and chemotherapy are two important methods for malignant tumor treatment. To research radiobiological response in therapy, we have established a better experimental method in contrast to the traditional ones such as TCD50, regrowth delay, cell survival curve, etc, all with their limitations. A new mouse tumor in vivo-in vitro system LA795 Vv-Vt has been developed for studies on radiobiology. Such a system could be used to study the in vivo response of a solid tumor by the in vitro cloning assay. For the purpose of increasing the PE in vitro, LA795 Vv-Vt tumor line was purified through culturing the cells as a clonogenic spheroid. The spheroids were then injected into the flank of mouse subcutaneously for tumor growth. The in vivo-in vitro system LA795 Vv-Vt is an excellent model dissecting and analyzing the various factors which affect tumor development and determine the response of tumor to specific agent and regimens. PMID- 2921139 TI - Radiosensitizing activity of 1-alkyl-3-nitropyrrolo-(2,3-b)-pyridine derivative. AB - Radiosensitization characteristics of a newly synthesized N-(3,N' morpholinpropyl)-2-[3-nitropyrrolo-(2,3-b)-pyridine -1-yl] ethanoic acid amide and the chemical basis of the action were studied. Partition coefficient, radox potentials for the one electron reduction of the compound were determined. This was confirmed by studies on the radiosensitization effect and cytotoxicity of the compound tested in vitro using Chinese hamster V79 cells. The results show that the sensitizing efficiency for this compound is C1.6 at a concentration of 0.5 mmol dm-3, which is similar to MISO. Its toxicity was not lower than that of MISO or metronidazole. PMID- 2921140 TI - Radiation survival properties of cultured human gastric adenocarcinoma cells and the effect of AT-1727. AB - Tumor cells (SGC-7901) obtained from a human gastric adenocarcinoma have been examined with regard to their intrinsic sensitivity to gamma-irradiation and as to how this intrinsic sensitivity might be altered by growth in a synthesized agent AT-1727 (N4-morpholino-methyl-3,5-dioxopiperazynyl-1,2 ethanl). Clonogenic survival was measured via colony formation assays and fitted to single-hit multitarget formula. Exponentially growing cells exhibited the mean of survival parameters: D0 = 0.86 + 0.04 Gy; n = 7.03 + 2.3; Dq = 1.63 + 0.23 Gy and SF2 (surviving fraction of conventional daily clinical dose of 2 Gy) = 45-50%. Split dose survival assays and delayed plating methods were used to exploit the capacity of sublethal damage repair of this cell line studied demonstrating the reappearance of initial shoulder on the survival curve and an increased survival. Alteration of radiosensitivity of SGC cells by AT-1727 was shown when cultures were incubated in a medium with the drug for a 6 hr interval between split dose irradiation, indicating the inhibition of sublethal damage repair. The radioresistance of hypoxic SGC cells was decreased when pre-treatment with AT 1727 was given 2 hr before irradiation, and the decrease of surviving fraction was drug-dose dependent. A maximum enhanced effect was obtained when 0.15 mM of AT-1727 was used, reaching an ER of 1.24. Inhibition of sublethal damage repair and action as a hypoxic radiosensitizer were considered to be two parts of the mechanism of AT-1727 in modification of radiation effects. PMID- 2921141 TI - Carcinoma of the urinary bladder category T2,3NXM0 treated by 40 Gy external irradiation followed by cesium137 implant at reduced dose (50%). AB - Forty-eight bladder cancers T2NXM0 with bad prognostic factors and 42 T3NXM0 growths, suitable for interstitial treatment, were submitted to 40 Gy external irradiation immediately followed by Cae137 Implant at "reduced dose". Intercurrent death corrected 5-year survival for both groups was about 80%. The influence of previously identified bad prognosticators (more than one TUR, WHO grade 3, 4, vascular invasion in the biopsy specimen, pathological IVP) was nearly eradicated. PMID- 2921142 TI - Radiotherapy for testicular seminoma stage I: treatment results and long-term post-irradiation morbidity in 365 patients. AB - After infradiaphragmatic radiotherapy the cancer-related 10 year survival was 99% in 365 patients with seminoma Stage I referred to the Norwegian Radium Hospital between 1970 and 1982. Thirteen patients relapsed, 11 of them within the first 3 years after treatment. Nine of the recurrent patients were cured by radiotherapy alone (4) or in combination with chemotherapy (5). There is no need to include the inguinal lymph nodes into the irradiation field or to give scrotal irradiation, not even to patients with tumor infiltration beyond the testicular tissue, or to those with prior scrotal or inguinal surgery. At least 1 year after radiotherapy moderate or more severe dyspepsia was observed in 16 patients. Nine patients developed a peptic ulcer. In general, there was no increased risk for development of a second non-germ cell cancer after radiotherapy. However, 4 patients developed a pulmonary cancer indicating a border-line significance of increased risk for this type of malignancy. (p:0.05). In conclusion, infradiaphragmatic radiotherapy remains the optimal routine treatment in seminoma patients with Stage I. PMID- 2921143 TI - Carcinoma of the uterine cervix stage IB and IIA: results of postoperative irradiation in patients with microscopic infiltration in the parametrium and/or lymph node metastasis. AB - One hundred and thirty-two patients received postoperative radiation therapy following radical hysterectomy and pelvic lymphadenectomy for carcinoma of the uterine cervix Stage IB and IIA. In 43 patients with negative lymph node the 5- and 10-year survival rate was 85%. The other 89 patients with positive lymph node had 5- and 10-year survival rates of 60% and 51%, respectively. Multifactorial analysis of prognostic factors in the group of patients with lymph node metastasis disclosed pathology, microscopic infiltration in the parametrium and vascular space invasion as independent prognostic factors, that is, the 5-year survival rates were: 66% for squamous cell carcinomas versus, 25% for adenocarcinomas (p value: 0.001), 76% negative parametrium versus 39% positive parametrium (p value: 0.008), 68% no vascular space invasion versus 43% if invasion was observed (p value: 0.04). Sites of failure in 37 recurrences out of 89 patients with lymph node metastasis were pelvic alone 9, distant metastases alone 15, and combined pelvic plus distant metastasis in 12 patients. In one patient the site of failure was unknown. These data warrant more intensive local and systemic treatment, particularly in patients with poor prognostic factors. In the whole group, severe complications were observed in 11 patients. PMID- 2921144 TI - Toxicity of open-field whole abdominal irradiation as primary postoperative treatment in gynecologic malignancy. AB - Between June 1979 and March 1985, 77 patients received whole abdominal radiation as the sole postoperative treatment for gynecologic malignancy. With an open field technique of irradiation, a median of 3,000 cGy was delivered to the entire abdominal contents with partial liver and kidney shielding; the total dose to the pelvis after boosts was 5,100 cGy, and that to the sub-diaphragmatic and para aortic nodal regions was 4,200 cGy. The primary sites of malignancy were the endometrium in 41 patients, ovary in 25, uterus in 5, fallopian tube in 4, and cervix in 2. Seven patients (9%), all older than 60 years, experienced acute gastrointestinal toxicity that interrupted treatment, only one of whom failed to complete the prescribed course as a result. Hematologic toxicity was sufficient to interrupt therapy in 21 patients (27%), 1 of whom failed to complete therapy as a result. Hematologic toxicity was not increased in elderly patients. All patients were followed up for a minimum of 30 months (median, 43 months) or until death. Six patients experienced a treatment-related bowel obstruction (two of whom had concomitant progressive intra-abdominal disease); the 3-year actuarial risk for a treatment-related bowel obstruction was 9%. This risk was significantly increased by high-dose boosting for residual disease. Only one instance of clinical radiation pneumonitis occurred, and no cases of clinical hepatitis were noted; however, subclinical evidence of pulmonary and hepatic radiation effect was frequent. Whole abdominal irradiation as described has modest toxicity for patients with gynecologic cancer who are at high risk for intra-abdominal failure. PMID- 2921145 TI - Intraperitoneal radioimmunotherapy for ovarian cancer: pharmacokinetics, toxicity, and efficacy of I-131 labeled monoclonal antibodies. AB - Thirty-six patients with ovarian cancer were treated with intraperitoneal I-131 labeled monoclonal antibodies to tumor associated antigens. The activity of I-131 administered was increased from 20 mCi to 158 mCi and the pharmacokinetics and toxicity evaluated. Five patients who had developed HAMA (Human Antimouse Antibodies) were retreated, and the pharmacokinetics and toxicity of the first and second treatment compared. Patients receiving their first therapy (HAMA negative), had a maximum of 25% (range 19.8-39.8%) of the injected activity in their circulation. This was accompanied by severe marrow suppression at I-131 activities over 120 mCi. The 5 HAMA positive patients had only 5% injected activity in the systemic circulation (range 3.8-6%), with rapid urinary excretion and neglible marrow suppression. In 31 patients with assessable disease there were no responses in 8 patients with gross disease (nodules greater than 2 cms), partial responses in 2 out of 15 patients with nodules less than 2 cms, and complete responses in 3 out of 6 patients with microscopic disease. The non specific radiation dose to the peritoneal cavity was estimated to be less than 500 cGy by lithium fluoride TLD, and could not be expected to account for the responses seen. PMID- 2921146 TI - The effect of hyperthermia on the early- and late-appearing mouse foot reactions and on radiation carcinogenesis: Part II. Effect on radiation carcinogenesis (thermal enhancement and oxygen enhancement). AB - The effect of hyperthermia on radiation carcinogenesis was investigated in the C3Hf/Sed mouse foot. The foot was irradiated under hypoxic conditions, in air, or under hyperbaric oxygen conditions to evaluate the oxygen effect. Hyperthermia at 43.5 degrees C for 45 min was given by immersing the animal foot into a constant temperature water bath. A malignant tumor in the irradiated foot was first observed congruent to 250 days after irradiation. Tumors developed in the irradiated area until day 850. RCD50, or 50% radiation carcinogenesis dose was the endpoint and was calculated based on the tumor incidence 650 days after irradiation. RCD50 following radiation given alone under hypoxic conditions was 66.3 (60.0-73.2) Gy, and the oxygen enhancement ratio (hypoxic/hyperbaric oxygen) was 3.0 (2.5-3.5). Radiation carcinogenesis was enhanced by hyperthermia given with a 20 min treatment interval with no significant alteration in the oxygen effect. Thermal enhancement was greatest when hyperthermia was given 20 min prior to irradiation (2.5 [2.2-2.9] under hypoxia). No thermal enhancement was observed when two treatments were given with a treatment interval of 2 days. The median time to develop a malignant tumor decreased with increasing radiation dose. This median time was shorter following combined hyperthermia and irradiation (423 days) than following radiation alone (504 days). Histological studies revealed that more than 80% of tumors were soft tissue sarcomas, and the most common tumor was fibrosarcoma. Squamous cell carcinoma was found in 7% of all tumors. PMID- 2921148 TI - Long-term survival and patterns of failure after postoperative radiation therapy for subtotally resected rectal adenocarcinoma. AB - Between 1977 and 1984, 17 patients received external beam irradiation after subtotal resection of rectal carcinoma. Ten patients had microscopic residual disease and 7 had gross residual disease. In the group with microscopic residual disease, 4 had tumor cut through with pathologically involved margins, 5 had adjacent unresected structures that were biopsy positive, and 1 had tumor spillage into the pelvis. The patients with gross residual disease were noted by the surgeon to have visible tumor after maximal debulking. Nine of 17 cases had involved pelvic lymph nodes. Radiation was administered to the pelvis with 4, 6, or 10 MV photons. Doses ranged from 40 to 60 Gy, with a median dose of 50 Gy given at 1.8 to 2.0 Gy per fraction, 5 days per week. Three patients received bacillus Calmette-Guerin (BCG), 2 received 5-fluorouracil (5-FU), and 1 received hycanthone. Thirteen of the 17 patients (76%) experienced local failure and, of these, 10 also developed distant disease. No patients developed distant metastasis in the absence of local failure. Local control was achieved in 3 of 10 patients (30%) with microscopic residual and 1 of 7 (14%) with gross residual. Four of the 17 patients (24%) have remained free of disease for greater than 5 years. External beam irradiation is capable of producing long-term survival and local control in a minority of patients with rectal cancer after subtotal resection. Investigation of more aggressive forms of therapy such as the addition of intraoperative irradiation, brachytherapy, radiation dose modifiers, and chemotherapy is warranted. PMID- 2921147 TI - Heat shock stimulates polyamine oxidation by two distinct mechanisms in mammalian cell cultures. AB - Heat shock stimulates both exogenous and endogenous polyamine oxidation in mammalian cells, but by distinct biochemical mechanisms. Exogenously added polyamines are oxidized in serum via the temperature-dependent activation of a single class of enzymes, the copper-dependent amine oxidases. Endogenous polyamines undergo a two-step reaction sequence involving acetylation by a heat inducible acetyltransferase and subsequent oxidation by a constitutively expressed, flavin-dependent polyamine oxidase. In both instances, polyamine oxidation generates hydrogen peroxide and reactive aldehydes which influence cell viability as demonstrated by inhibitor studies. Aminoguanidine, an inhibitor of the copper-dependent amine oxidases, confers protection to cells during either a severe 43 degrees C heat shock or a relatively nontoxic heat stress followed by incubation at 37 degrees C, all in the presence of exogenous spermidine. Specific inhibition of the endogenous polyamine oxidase will also confer partial survival protection after heat shock, but only in cultures that have been previously depleted of cellular glutathione. These data confirm that hyperthermic stress can generate an oxidative stress in mammalian cells via induction of polyamine oxidation. Further, through distinct extracellular and intracellular mechanisms, these temperature-dependent polyamine oxidation reactions can modulate cell viability. PMID- 2921149 TI - Nasopharyngeal carcinoma with dermatomyositis. AB - From 1976 to 1986, ten out of 1154 consecutive nasopharyngeal carcinoma (NPC) patients were found to have dermatomyositis (DM). Their clinical features and treatment results were analyzed. The skin manifestation was typical of DM and myopathy occurred in seven patients. All the tumor on presentation were early stage and locoregional control after radiotherapy was satisfactory. All but one patient had DM prior to diagnosis of NPC. The prognosis of NPC was not affected by DM with survival being comparable to contemporary controls. The complication of radiotherapy were unusually severe. Chronic radiation skin ulceration occurred in 2 patients and subcutaneous indurated fibrosis affecting both sides of neck occurred in all patients. Acute radiation mucositis was also prominent. PMID- 2921150 TI - Radiation therapy of keratoacanthomas: results in 55 patients. AB - The radiation therapy of keratoacanthomas in fifty-five patients treated between 1976 and 1986 using orthovoltage X rays (contact and soft X ray therapy) is reported. The total dose delivered was 40 Gy by means of twice weekly fractions of 4 Gy each in 52 cases, and 60 Gy by twice weekly fractions of 5 Gy each in 3 cases with notable cellular atypia. In all cases we obtained complete regression of the lesions irradiated within 1 month after the termination of radiotherapy. So far we have not had any recurrences. The cosmetic result was always satisfactory. We should like to point out the association between keratoacanthomas and a second malignancy in two cases. The role of radiotherapy in the treatment of keratoacanthomas is discussed and re-confirmed, in relation to the literature data. PMID- 2921151 TI - Results of postoperative irradiation of medulloblastoma in adults. AB - This study analyzes the results of combined surgery and radiation therapy in 13 cases of medulloblastoma in adults treated at the Institute of Oncology in Cracow between 1974-1980. There were 5 women and 8 men. The mean age of the patients was 22.4 years. The overall crude 5-year survival was 62%. Four patients developed recurrence at the primary site (in one case local recurrence was concurrent with pulmonary metastases). The posterior fossa dose in these patients was 2625, 3000, 4800, and 5000 cGy. All 5-year survivors received the posterior fossa dose ranging from 5000 to 5400 cGy. For optimal local control the posterior fossa dose of at least 5400 cGy is recommended, with prior irradiation of the whole cranio spinal axis. PMID- 2921152 TI - Evaluation of treatment results of squamous cell carcinoma of the buccal mucosa. AB - Of the 49 patients with squamous cell carcinoma of the buccal mucosa referred to the Rotterdam Radio-Therapeutic Institute (RRTI) and Universital Hospital Dijkzigt Rotterdam (AZD) during 1970-1984, 31 patients had an advanced stage of disease, 21 patients had clinical evidence of lymph node metastasis. Forty patients were treated with curative intention. Treatment modalities were: radiation therapy, preoperative radiation followed by surgery, and primary surgery. Eighteen of the 40 patients (45%) developed a local tumor recurrence; nearly all recurrences occurred within 2 years. The incidence was equal in all treatment groups. Of the 22 patients with initial clinically negative neck, regional relapse occurred in 3 of the 14 patients, of whom the neck was not treated electively by radiation therapy; all three in combination with a local recurrence. None of the 8 patients with electively irradiated necks developed a regional relapse. Eight of the 18 patients with initial clinically enlarged lymph nodes treated either by radiotherapy or surgery, developed a regional relapse, 5 in combination with a local recurrence. Treatment of the clinically positive neck by neck dissection was superior to radiotherapy. Local recurrence carried a poor prognosis. Almost 70% died of their disease. The overall and corrected 5-year survival was 38% and 52% respectively. PMID- 2921153 TI - Improvements in brachytherapy quality assurance. AB - Quality assurance (QA) for a busy brachytherapy service is a demanding task which requires the involvement of the entire brachytherapy team. This communication describes the QA program for brachytherapy procedures and source identification and inventory which is currently practiced at the Radiation Oncology Center, Mallinckrodt Institute of Radiology. PMID- 2921154 TI - Comparison of automated and manual shielding block fabrication. AB - This work reports the results of a study comparing computer controlled and manual shielding block cutting. The general problems inherent in automated block cutting have been identified and minimized. A system whose accuracy is sufficient for clinical applications has been developed. The relative accuracy of our automated system versus experienced technician controlled cutting was investigated. In general, it is found that automated cutting is somewhat faster and more accurate than manual cutting for very large fields, but that the reverse is true for most smaller fields. The relative cost effectiveness of automated cutting is dependent on the percentage of computer designed blocks which are generated in the clinical setting. At the present time, the traditional manual method is still favored. PMID- 2921155 TI - Conformation therapy to improve the irradiation of the spinal axis. AB - Techniques for the irradiation of the spine have remained largely unchanged since the introduction of megavoltage therapy. The main disadvantages of these techniques are the inhomogeneous dose distribution and the problems associated with field joins. The tracking method of conformation therapy employs a short field length and translates the patient through the beam on the couch of a computer controlled treatment unit. Dose uniformity along the spinal axis is achieved by controlling the speed at which the target travels through the radiation field. Treatment is given at standard source-axis distance (SAD) and the need for external shielding is eliminated by shaping the width of the field. The join with the cranial fields is independent of any skin marks, removing the risk of over- or under-dosage. Treatments are planned automatically from computed tomography (CT) information by an in-house planning system. The calculated doses have consistently shown good agreement with phantom measurements. Three cobalt dose distributions are presented and compared: a tracking treatment; a single posterior field, and two matched fields. The superiority of conformation therapy over the other commonly used treatment methods is clearly demonstrated. PMID- 2921156 TI - Tandem tip fracture: a rare complication of intracavitary therapy of cervix cancer and how to avoid its occurrence. AB - A case is described in which the distal tip of a tandem fractured off in a patient's uterus during an intracavitary application of a tandem and ovoids. Potential contributing factors are evaluated. Methods to prevent and detect structural defects in tandems before they become clinically manifest are discussed. PMID- 2921157 TI - The proportion of stem cells in murine tumors. AB - Considerable evidence suggests that tumors contain only a minority of cells which are capable of regrowing the tumor (ie. tumor stem cells). Since all tumor stem cells must be killed if treatment is to be successful, the number of stem cells in a tumor can be expected to be an important determinant of curability. We have attempted to examine the proportion of stem cells in a variety of murine tumors by making measurements of three different parameters which might be expected to be related to stem cell content: (a) the radiation dose required to control the tumor (TCD50); (b) the number of cells required to transplant the tumor (TD50) and (c) the in vitro plating efficiency. An inverse correlation has been demonstrated between measured TCD50 and TD50 values for two independent groups of murine tumors of varying histopathological type. An inverse correlation was also obtained between the TD50 value and in vitro plating efficiency for a group of spontaneous murine mammary tumors. These correlations most likely reflect underlying differences in the stem cell content of the tumors, and indicate that there is a wide range (2-3 orders of magnitude) of stem cell proportions in different murine tumors, even those which have been transplanted a number of times. PMID- 2921158 TI - Radiation therapy technology: manpower survey 1987. AB - A chronic shortage of radiation therapy technologists exists in the United States. This report presents the data obtained in a 1987 survey of all radiation oncology facilities identified by the Patterns of Care master list. Of the 1,142 questionnaires mailed, 52% were returned. The survey identified 2,328 credentialed (ARRT) and 554 non-credentialed technologists employed in radiation therapy. Of this total of 2,882, 2,141 were identified as staff technologists. A total of 1,186 megavoltage units were identified, giving a ratio of 1.8 technologist/megavoltage unit. Two hundred sixty open funded positions and 230 unfunded positions for radiation therapy technologists were identified. The report compares the results of this 1987 Radiation Therapy Technology Manpower Survey with the results of the three previous surveys conducted in 1975, 1977, and 1981. Whereas this comparison demonstrates that progress has been made, current trends in allied health education are expected to have a negative impact on recruitment into radiation therapy technology. Program directors report that the number and quality of applicants to all allied health education programs is declining, and this trend in radiation therapy technology is substantiated by a drop in the number of students enrolled in programs, from 970 in 1986-87 to 777 in 1987-88. Our discussion addresses the areas of new program development, recruitment, retention, innovative programs, and overseas recruitment. PMID- 2921159 TI - Early onset acute radiation toxicity and amiodarone. PMID- 2921161 TI - Optimization of the absorbed power distribution for an annular phased array hyperthermia system. AB - One of the systems under investigation for producing hyperthermia noninvasively for treating deep-seated tumors is the annular phased array. This device consists of two rings of eight electromagnetic apertures that are placed concentrically about the long axis of the patient and radiate energy toward the center. Previous theoretical and clinical studies have concentrated primarily on systems where the amplitude and phase of the signal applied to each aperture were the same, and these studies have shown that the system is capable of depositing power deep within the patient. Nevertheless, in many situations the system was not capable of producing desirable temperature distributions in the tumor and normal tissue. In this paper we report on a 2-dimensional theoretical investigation where an optimization routine was used to select the amplitude and phases of each of eight apertures. The optimization procedure and resulting calculations were based on CT scans of patients with tumors. The electrical and thermal properties of the different organs and tissues were taken into account. The optimization routine tried to achieve uniform absorbed power in the tumor region with zero absorbed power outside. Using the optimized amplitudes and phases, the SAR (specific absorption rate, W/kg) was calculated for the array. The results show that in general the optimization procedure was successful in that the power deposited within the tumor volume was increased with less power deposited into normal tissue when compared to the equal amplitude and phase case. This SAR data was then used as the input to a program based on the bioheat transfer equation, which calculated the temperature distribution in the patient model for an assumed set of blood perfusion rates. Depending on the location, size of the tumor, and blood perfusion rates, the improvement in the percentage of the tumor brought to therapeutic temperature varied from 0% to as much as 80%. PMID- 2921160 TI - Hyperthermia quality assurance guidelines. AB - These Hyperthermia Quality Assurance guidelines are a result of a joint workshop of the Hyperthermia Committee of the American College of Radiology and the Hyperthermia Physics Center, which is the national quality assurance program under Contract No. N01-CM-37512 with the National Cancer Institute. Hyperthermia technology presently lacks the kind of standardization in equipment, treatment procedures, patient monitoring, and treatment documentation available in radiotherapy. Therefore, preventing unacceptable variability in treatment data demands a strong commitment to in-house quality control procedures and to centralized quality assurance reviews in cooperative multi-institutional trials. This paper presents a set of test procedures necessary to ensure proper operation of equipment, suggests a frequency for such tests, and also includes guidelines on quality control procedures to be used during treatment to improve the safety, effectiveness, and reproducibility of hyperthermia treatments. A set of forms are presented to indicate the minimum data, albeit incomplete, that must be collected for acceptable documentation of treatment. These guidelines should be valuable not only to the new entrants in the field but also to those participating in multi-institutional cooperative hyperthermia trials. They have been approved by the Hyperthermia Committees of American College of Radiology, American Society for Therapeutic Radiology and Oncology, Radiation Therapy Oncology Group and the American Association of Physicists in Medicine. PMID- 2921162 TI - Improved coupling of ultrasound hyperthermia applicators to patients. AB - Coupling ultrasound (US) hyperthermia (HT) applicators to patients requires an acoustical medium conforming to both applicator and patient that allows for rapid, reproducible set-up for each treatment and prevents drift or misalignment of the applicator during treatments. We describe a technique that uses a commercially available immobilization foam to create a rigid, conforming foam block that kinematically positions the US applicator over the tumor area. The central volume of the foam block is removed and filled with a plastic bag of degassed water or with US gel during treatments. We also describe a technique for positioning surface and interstitial thermometry sensors in alignment with individual elements of a multi-element US applicator. Using these techniques, relative movement between patient and applicator is minimized, correct thermometry sensor location relative to each US element is confirmed, and efficient transmission of the acoustical power into the target volume is assured. These techniques are particularly important when using multi-element applicators with complex temperature-power control algorithms. PMID- 2921163 TI - A proposed standard data file format for hyperthermia treatments. AB - One of the most critical areas of research essential to improve the clinical use of hyperthermia in cancer therapy is the determination and evaluation of temperature during therapy. In order to improve the dissemination of newly developed thermometry measurement and analysis programs and facilitate the transport of hyperthermia data files between computers for both intra- and inter- institutional use, we propose a standard file format, the Hyperthermia Data Standard (HDS), which can be used for all hyperthermia data. This data file consists of segments of which nine have been defined. The first is an initial /VERSION segment which identifies the file standard. This is followed by eight major segments: 2) a /IDENT segment which contains file and patient identification information; 3) a /TEXT segment containing additional miscellaneous documentation; 4) a /TUMOR segment which provides tumor and treatment site information; 5) a /HSETUP segment which contains treatment setup information; 6) a /FORMAT segment which defines the data segment structure; 7) a /DATA segment containing the actual thermometry data; 8) a /FOLLOWUP segment for documenting patient response; and 9) an /ANALYSIS segment containing summary information. All segments begin and end with a specified delimiter and, except for the first two (/VERSION and /IDENT), may be repeated more than once. For ease in debugging and verifying adherence to the standard, all information in the file is encoded in printable ASCII characters. All segments consist solely of records containing KEYWORDS and KEYWORD VALUES which identify specified information. Certain KEYWORDS are standard, i.e., having specified names and information formats as defined in this document. The /DATA segment consists of ASCII encoded chronological treatment thermometry and other data whose format and structure is identified in the /FORMAT segment. The /ANALYSIS segment provides the flexibility to store the results of any analysis program along with the actual data file for ease of data management. This thermometry data file standard is designed to provide both flexibility and extendability for all possible forms of hyperthermia treatment data. Furthermore, it is designed to provide a simple format which may be easily read by higher level languages. This document is intended for commercial manufacturers and others who are writing programs to document clinical hyperthermia treatments with the intention that they either use this format for their data storage or provide a means to convert their data into this format.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2921164 TI - Local-regional recurrence in breast cancer after mastectomy and adriamycin-based adjuvant chemotherapy: evaluation of the role of postoperative radiotherapy. AB - In an attempt to determine whether patients treated for breast cancer with radical or modified radical mastectomy and adjuvant chemotherapy benefit from postoperative radiotherapy, 400 women with Stages II-III breast cancer who received adjuvant chemotherapy based on the combination of Adriamycin and Cytoxan were analyzed retrospectively. Prognostic features which predicted a high risk of isolated local-regional relapse were identified. Thirty-eight percent of these patients were also treated with postoperative radiation in addition to adjuvant chemotherapy and were compared to those patients treated only with adjuvant chemotherapy. With a median follow-up of 60 months, 15% of the patients reviewed developed local-regional disease as the first site of relapse without concommitant systemic relapse. When examined univariately, stage of disease, tumor size, nodal status, and estrogen receptor status were strong prognostic variables. Age, cell type, location of tumor within the breast, menstrual status, radiation dose, and type of treatment were not significantly related to isolated local-regional relapse. However, patients who received postoperative radiation were significantly more advanced in their disease condition. When the factors were examined multivariately, the type of treatment along with stage of disease were found to be statistically significant prognostic indicators. About half of the patients were tested for estrogen receptor status. Multivariate analysis performed on this subset of patients showed that estrogen receptor status, type of treatment, and axillary nodal status were significant predictors of the risk of isolated local-regional relapse. This study suggests that patients treated with mastectomy and Adriamycin and Cytoxan-based adjuvant chemotherapy may benefit from postoperative radiation in reducing the risk of isolated local regional recurrence. PMID- 2921165 TI - Postoperative radiotherapy of supratentorial low-grade gliomas. AB - Forty-nine patients with supratentorial low-grade gliomas underwent surgery (biopsy or subtotal resection) and postoperative radiotherapy at the Mayo Clinic between 1976 and 1983. The median, 5-, and 10-year overall survivals for the total group were 6.5 years, 62%, and 14%, respectively. Nine prognostic variables were examined for their possible association with survival, including age, sex, site, size, CT enhancement, histologic type, extent of resection, radiation volume, and radiation dose. Of these variables, only histologic type was significantly associated with survival. The estimated 5-year survival was 100% for the 5 patients with pilocytic astrocytomas, 83% for the 20 patients with oligodendrogliomas or mixed oligo-astrocytomas, and 40% in the 24 patients with ordinary astrocytomas (log rank p = 0.001). Other possible prognostic variables, such as radiation volume or total dose, showed no association with survival. Twenty-seven patients had a documented treatment failure. For the 20 patients in whom the pattern of failure could be determined, all failed within their radiation portals. Eleven patients had additional tissue obtained following suspected disease recurrence. Tumor was found in ten of these patients, and radionecrosis in one. PMID- 2921166 TI - Radiation tolerance of the cervical spinal cord. AB - The incidence of permanent injury to the spinal cord as a complication of radiation therapy generally correlates positively with total radiation dosage. However, several reports in the literature have indicated that fraction size is also an important factor in the development or nondevelopment of late injuries in normal tissue. To determine the effect of fraction size on the incidence of radiation-induced spinal cord injuries, we reviewed 144 cases of head and neck cancer treated at our institution between 1971 and 1980 with radiation greater than 5600 cGy to a portion of the cervical spinal cord. Most of these patients received greater than or equal to 6000 cGy, with fraction sizes ranging from 133 cGy to 200 cGy. Fifty-three of the 144 patients have been followed up for 2 years or more. Nearly half of these (26 patients) received greater than 6000 cGy with fraction sizes of 133 cGy to 180 cGy. Only 1 of the 53 (1.9%) has sustained permanent spinal cord injury; 20 months after completion of radiation treatments he developed Brown-Sequard syndrome. Our experience suggests that radiation injuries to the spinal cord correlate not only with total radiation dosage, but also with fraction size; low fraction sizes appear to decrease the incidence of such injuries. PMID- 2921167 TI - Biological effectiveness of fast neutrons on a murine osteosarcoma. AB - The effect of fast neutrons and gamma rays on a murine osteosarcoma was studied. The NROS tumor, a radiation-induced osteosarcoma in a C3H mouse, was transplanted into the right hind legs of syngeneic female mice and locally irradiated with single or four daily doses of either fast neutrons or gamma rays. The NROS contained 13-30% hypoxic cells. It took approximately 7 days for the NROS tumor to show apparent reoxygenation following gamma ray irradiations. Two assays were used to determine the neutrons' relative biological effectiveness (RBE) to gamma rays: tumor growth delay time and tumor control dose. The largest RBE of 4.5 was obtained at the smallest dose of neutrons examined, followed by a gradual decrease down to 2.3. The tumor growth delay assay indicated that the RBE values of 2.6-3.1 after single doses of fast neutrons increased to 3.1-4.5 after four daily fractions. The 50% tumor control doses were 78.5 Gy and 33.0 Gy after single doses of gamma rays and fast neutrons, resulting in an RBE of 2.3. Fractionated doses increased the RBE to 2.6. Mitotic cells disappeared shortly after irradiation but reappeared 7 days after irradiation. PMID- 2921168 TI - Radiotherapy of the rhabdomyosarcoma R1H of the rat: hyperfractionation--126 fractions applied within 6 weeks. AB - The effect of a hyperfractionated irradiation treatment on the response of the rhabdomyosarcoma R1H of the rat was studied. Tumors were irradiated under ambient conditions with 126 fractions of X rays, applied in 3 fractions per day with a time interval of 8 +/- 1 hr between fractions on 7 days per week during 6 weeks. The total dose ranged from 54 to 90 Gy, that is the dose per fraction ranged from 0.43 to 0.71 Gy. Tumor response was assessed by tumor control probability and tumor net growth delay. The tumor response to the hyperfractionated treatment was found to be slightly more effective compared to the results obtained in a previous study where treatments with 6, 18, 30, and 42 fractions were applied. Since normal tissues are considerably spared with increased numbers of fractions, clinical studies with hyperfractionation seem to be very promising. PMID- 2921169 TI - The effects of tumor mass, tumor age, and external beam radiation on tumor specific antibody uptake. AB - The effects of external beam radiation on tumor uptake of radiolabeled monoclonal antibody were investigated. Nude mice bearing carcinoembryonic antigen (CEA) producing subcutaneous human tumor xenografts (LS174T) were irradiated (60Co) with a single fraction of 0, 2 or 20 Gy, 6 or 11 days after tumor inoculation. An Indium-111 labeled anti-CEA monoclonal antibody (T84.66) was injected 1-2 hrs after irradiation. Biodistribution studies performed at 48 hrs showed a statistically significant (p less than 0.01) inverse correlation between tumor mass and tumor antibody uptake. Tumor age was also a significant factor with 11 day old tumors having significantly less uptake (p less than 0.0001) compared to 6 day old tumors for a given mass. Radiation increased tumor antibody uptake only in those tumors where growth inhibition also occurred. Multiple regression analysis showed that this inverse correlation between tumor mass and antibody uptake was the same for irradiated and nonirradiated tumors. We conclude that, in this model system, radiation does not act independently to enhance tumor antibody deposition. Radiation's primary effect is to reduce tumor mass, with mass reduction then resulting in an increase in antibody uptake. The clinical implications of this study are discussed. PMID- 2921170 TI - Studies concerning the effect of external irradiation on localization of radiolabeled monoclonal antibody B72.3 to human colon carcinoma xenografts. AB - Recent studies in animal models involving antibody tumor targeting of hepatoma and melanoma and clinical trials involving hepatoma patients have suggested that preirradiation of tumors may enhance antibody tumor targeting. These reports led us to study the effect of external irradiation on monoclonal antibody (MAb) targeting of human carcinomas; as a model system, we used MAb B72.3 and the LS 174T human colon carcinoma xenograft in athymic mice. LS-174T tumors exposed to 300 cGy grew to approximately 93% the size of non-irradiated tumors, while those exposed to 600, 900, or 2,000 cGy were approximately 41% the size of control tumors. Splitting the 900 cGy into three 300-cGy fractions yielded a two-fold lower tumor volume compared with a single 900-cGy fraction. Histochemical evaluation of the carcinomas revealed a decrease in the number of mitoses per high power field consistent with early effects of radiation exposure. Using the avidin-biotin complex immunoperoxidase technique, carcinomas were assayed for expression of the tumor associated glycoprotein (TAG)-72, the high-molecular weight mucin detected by MAb B72.3. No discernable variation was observed in the staining intensity among tumors in both the control and radiation treated group; that is, differences among tumors within each group were compatible with the known heterogeneous expression of TAG-72. Exposure of carcinomas to 300 or 900 cGy in a single fraction or 900 cGy split in three 300-cGy fractions did not yield a consistent or substantial enhanced localization of radiolabeled MAb B72.3 IgG or F(ab')2 to tumors. A 1.5-fold augmentation of MAb binding to tumors was observed in preirradiated mice; however, these results were not statistically significant. Inherent differences in tumors such as cell type of origin, size, spatial configuration, extent of vascularization and volume of interstitial space may contribute to variability of the effect of preirradiation of tumors on antibody binding. Our results suggest that consistent augmentation of radiolabeled antibody localization to tumors is not a universal phenomenon. PMID- 2921171 TI - Tumor imaging of Dalton's lymphoma using antibody-desferal-Ga-67 complex. AB - Using desferal, a bifunctional chelating agent, Ga-67 was conjugated to the antibody, anti DLAA, specific for a 80 KD antigen associated with Dalton's lymphoma (DLAA) and was used for imaging of murine lymphomas induced by an 'air pouch' technique. Scintiscan studies were carried out at 24 hr, 48 hr, 72 hr, after i.v. administration of Ga-67-anti DLAA-DF complex and compared with scintigrams obtained after administration of free Ga-67 citrate and suspension of Ga-67, DF, anti DLAA to different batches of tumor bearing mice. The study was also carried out using mouse IgG, a non-specific antibody, instead of anti DLAA. The results were compared with biodistribution studies. Scintigrams demonstrated that with anti DLAA there was maximum uptake of Ga-67 by the tumor providing the best images. PMID- 2921172 TI - Adhesion formation in experimental chronic radiation enteropathy. AB - We have studied the late changes associated with radiation enteropathy in mice over a period of 224 days following single or split doses of gamma radiation delivered to the total abdomen (TAI). We focused on the importance of adhesion formation as a cause of strictures and gut-associated deaths following TAI. Gut associated peritoneal adhesions were found in mice 2-7 months after receiving 13.5-17.5 Gy TAI and appeared to constitute the most consistent serious late effect of irradiation. There was a good correlation between adhesion formation and death for both the single and split-doses of radiation. Adhesions primarily involved the large gut, normally near the cecum. They appeared to result from serosal breakdown and were the major cause of partial gut obstruction. Submucosal fibrosis was present but seemed to be a comparatively minor cause of strictures. Local lymphoid hyperreactivity was also seen following TAI and may have contributed to the late sequelae. The complexity of the pathogenesis of chronic radiation enteropathy was indicated by finding three successive waves of non scheduled deaths following TAI. The first wave (28-70 days) was not related to adhesion formation and may have been due to localized failure of mucosa to regenerate after irradiation with consequent ulceration. The second wave (98-140 days) occurred over the period when adhesion formation and fibrosis were most marked. In the third wave (168-224 days), the additional complication of fluid exudation was seen. Further experimentation is obviously needed to better define the complex pathogenesis of radiation enteropathy with dose and time after radiation but our data strongly support a multifactorial causation with an important role for adhesion formation in the disease complex. PMID- 2921173 TI - Lung density changes observed in vivo in rat lungs after irradiation: variations among and within individual lungs. AB - Lung density measurements using Computed Tomography have been used before at various intervals after irradiation to monitor radiation-induced changes in the lung. The average lung density, its standard deviation which was used as a measure of the density homogeneity throughout the lung, and the densities of smaller lung regions were measured before and up to 76 weeks after irradiation in rat lungs. Large differences in individual response to irradiation were observed. Both increases and decreases in lung density were measured. Regions of very low density were often found adjacent to dense foci of radiation damage. These compensatory changes made the measurement of changes in average lung density an insensitive index of radiation damage. However, the measurement of regional densities in smaller lung volumes, a method not previously applied to rodents, was a much more sensitive index of radiation damage. Changes from non-irradiated control lung densities were observed at earlier times and for lower radiation doses. PMID- 2921174 TI - Misonidazole binding in SCCVII tumors in relation to the tumor blood supply. AB - Misonidazole (MISO) binding was examined in murine squamous cell carcinomas as a function of distance from the tumor blood supply. C3H mice bearing subcutaneous SCCVII tumors were injected intraperitoneally with 3H-MISO followed at various times later by intravenous injection or infusion of the fluorescent perfusion probe, Hoechst 33342. Tumors were then excised, and single cell suspensions prepared for fluorescence activated cell sorting. Cells sorted on the basis of Hoechst 33342 fluorescence were examined for 3H-MISO content by liquid scintillation counting or autoradiography. MISO content in the 10% of cells most distant from the blood supply was as much as 8 times greater than the amount in the 10% of cells closest to the blood supply. The largest differentials in MISO content between dimly and brightly staining regions were obtained if (a) tumors greater than about 300 mg were used, (b) at least 3 hr were allowed for MISO metabolism and binding prior to analysis, and (c) cell sorting was performed on the basis of concentration of Hoechst (correcting for cell size) rather than on the basis of total fluorescence intensity per cell. As tumors enlarged, MISO content increased even in the cells closest to the blood supply suggesting a decrease in net tumor oxygenation perhaps caused by intermittent hypoxia. PMID- 2921175 TI - Dose fractionation and regeneration in radiotherapy for cancer of the oral cavity and oropharynx: tumor dose-response and repopulation. AB - In a retrospective study, local control of the primary tumor in 498 squamous cell carcinomas of the oral cavity and oropharynx was analyzed with respect to initial tumor volume, total dose after normalization for variations in fraction size, and to overall treatment time. Primary tumors were grouped into 4 sites, tongue (175), oral cavity including floor of mouth, faucial pillar, soft and hard palate and gingiva (210), tonsil (72) and buccal mucosa (41). Total doses of 60Co irradiation ranged from 30 Gy to 72 Gy, overall treatment times from 15 to 80 days and dose per fraction from 1.8 to 6 Gy. The large number of patients and diversity of dose fractionation patterns permitted assessment of the independent contributions to treatment outcome of stage, fraction size and overall treatment duration. The following conclusions were drawn: (1) Overall treatment time influenced strongly the probability of local tumor control. Over the interval of about 30-55 days used in treating most of this series of patients, an increase of 60 cGy per day, on average, was required for a constant control rate. (2) The increase in dose was attributed to accelerated tumor clonogen growth rate. Such accelerated growth could be a major determinant of failure in protracted regimens. (3) The accelerated rate of regrowth was similar for all tumor sites and stages. (4) The dose for tumor control was relatively independent of variations in fraction size within a range of about 1.6 Gy to 3 Gy: the alpha/beta value in the linear quadratic isoeffect equation was at least 15 Gy. (5) Local control at the primary site required an average of about 3 Gy more for each increase in T stage. This increase most likely reflected an increased number of tumor clonogens, not a decreased tumor cell radiosensitivity. (6) The probability of control at the primary site was less likely if lymph nodes were positive, but this association was only shown to be statistically significant for primaries classified here as oral cavity and oropharynx, not tonsil, tongue or buccal mucosa. (7) After allowing for differences in treatment parameters, especially for heterogeneity in overall treatment times, tumor control probability increased steeply with increase in total dose. (8) A general principle of radiotherapy, at least for squamous carcinomas of head and neck, should be to deliver the desired fractionated dose regimen without unnecessary interruptions and in the shortest time compatible with no reduction in dose below that tolerated by the late-responding normal tissues. PMID- 2921176 TI - Dosimetric evaluation of a variable energy superficial X-ray machine with applications for endocavitary radiotherapy techniques. AB - This investigation presents the beam characteristics of a newly-marketed variable energy superficial X ray machine for radiotherapy. The X ray system hardware, including a high voltage generator, and console software allow for nine independent operator-selected X ray beams from 10-150 kVp. Filament current values are also independently variable; 1.0-13.0 mA for 90-150 kVp, and 1.0-30.0 mA for 10-90 kVp. The HVL's, effective energies, and radiation outputs for the nine combinations of kVp and mA are presented. In addition, percentage depth dose and beam uniformity results are presented as a function of cone size. Radiation output stability and reproducibility results are included. Discussion of adaptation of this X ray system to the Papillon technique for the treatment of rectal cancers is presented. PMID- 2921177 TI - Simulating blocks in treatment planning calculations. AB - It is difficult to make an accurate calculation of dose distribution incorporating blocks using a ray model. One approach is to simulate the blocking in a treatment planning distribution by using negatively weighted beams. A second is to employ an external contour. The parameters of the negative beam or contour can be adjusted using empirical dosimetric data. This paper discusses the calculation of the dose distributions using negatively weighted beams and external contours, compares them with measurements in and around blocked areas for a range of field sizes, block sizes, and depths of interest in treatment planning applications, for 60Co, 6 MV, and 10 MV beams, and assesses their applicability. PMID- 2921178 TI - If we can't define the quality, can we assure it? PMID- 2921179 TI - Reply to editorial by James Oleson, M.D., PH.D. PMID- 2921180 TI - Low dose prophylactic irradiation in metastatic breast cancer: possible roles of cell killing versus tumor bed effect. PMID- 2921181 TI - Pelvic node irradiation. PMID- 2921182 TI - The influence of pelvic node irradiation on prognosis. PMID- 2921183 TI - Sexual behavior and contraceptive risk taking among sexually active adolescent females. AB - Drawing on DeLamater's conceptual model of premarital contraceptive activity, this study assessed the relationships between various social, developmental, and behavioral variables and contraceptive risk taking by sexually active adolescent females. The hypotheses were tested on a national random sample of unmarried sexually active adolescent females (n = 1512) ages 15-20 years from Cycle III of the National Survey of Family Growth. The number of years the subjects had been sexually active was the strongest predictor of their frequency of sexual intercourse, followed by their frequency of attendance at religious services. The inverse relationship between religious attendance and coital frequency was much stronger among whites than blacks. When the influence of these variables on contraceptive risk taking was assessed, coital frequency explained 7.2% of the variation in contraceptive risk taking, with the number of years the adolescent had been dating explaining a small amount of additional variation. Our data support not only the first stage of DeLamater's conceptual model of premarital contraceptive activity, but also aspects of Jessor's more general theory of adolescent risk taking and problem behavior. PMID- 2921185 TI - Psychosocial and clinical variables in pregnant adolescents. A survey of maternity home residents. AB - Substantial research exists about pregnant adolescents, but there are few studies focusing on this population in residential maternity homes. This survey was designed to gather data about demographic and clinical characteristics, self esteem, and social support available to adolescents in two maternity homes in Los Angeles. Adolescents' attachment to their unborn fetus was also evaluated. The culturally diverse sample included 90 unmarried subjects between 14 and 19 years of age. Results suggest that adolescents in maternity homes possess many of the same attributes as pregnant adolescents in the larger community. Self-esteem scores of residents of the Self-Esteem Inventory (mean = 66.67) were similar to those reported in other studies of pregnant adolescents. There was great variation found in the quantity and quality of functional social support received by residents. Family (97.8%) and friends (78.8%) were identified as significant individuals in the social network of the residents. Although the majority of adolescents had not planned their pregnancy, their scores on the prenatal attachment questionnaire supported a positive affiliation with their fetus. Based on these findings, recommendations are offered for programs to facilitate the development of self-esteem and support-enhancing skills of pregnant adolescents living in residential maternity homes. PMID- 2921184 TI - The relationship between maternal weight for height and term birth weight in teens and adult women. AB - Many factors may contribute to the high rates of low birth weight observed in most studies of teen pregnancy. This study examined the contribution of low prepregnancy weight and low gestational weight gain, both of which are more common in teens than in adults. Records were obtained for 90 primiparous teens (less than 16 years old at conception) and 90 primiparous adult women (19-30 years old at conception) delivering at St. Luke's Hospital in New York City. Women were matched for year of delivery and clinic payment status. Mean birth weight was 264 g lower in the teen group than in the adult group. In both groups, birth weight increased with increased maternal prepregnancy weight, weight gain, and percent of standard weight for height at term. In adults, birth weight plateaued when maternal weight for height was 120% or more of standard. In teens, however, birth weight was 200-400 g lower than in the adults in all weight-for height categories except at 140% or more of standard. Both the low birth weight rates and the portion of infants weighing less than 3000 g were much higher in the teen mothers. Thus, even if maternal weight at term is appropriate for height, teen mothers have smaller babies than adult women do. PMID- 2921186 TI - Group therapy with adolescent cancer patients. AB - This preliminary study assessed the psychologic distress and group psychotherapy of a small group of adolescents and young adults with cancer. A strong relationship was found between the patients' and parents' amount of psychologic distress. It seems that youngsters with cancer in active medical treatment (as well as their parents) use more denial and that psychotherapy increases psychologic distress. PMID- 2921187 TI - Nipple (papilla) development in girls: III. The effects of pregnancy. AB - Previous cross-sectional and longitudinal studies of girls have documented that they have a significant growth in nipple size during Tanner stages pubic hair (PH)4 and PH5 or breast (B)4 and B5. This study assesses whether there is any effect of pregnancy on nipple development in adolescent girls. Thirty-three pregnant girls were compared to a previously reported group of 390 girls who were not pregnant. Of the 33 girls, ten were followed longitudinally for a period of nine to 79 months, during which time they became pregnant. In each girl, nipple diameter was measured and the Tanner stage assessed. A markedly significant increment in nipple size was noted in the girls who were pregnant (pregnancy nipple size 12.6 mm vs. PH5 9.7 mm and B5 9.9 mm). Comparison of ten girls prior to and during pregnancy revealed a significant increment as well (10.2 mm vs. 12.8 mm, respectively). Pregnancy provides a further stimulus for nipple development in girls beyond that which occurs during normal puberty. PMID- 2921189 TI - Dentists' professional satisfaction with adolescent dentistry and its association with adolescent dental health behavior. AB - This study examines dentists' perceptions of behaviors felt to interfere with providing adequate dental care to adolescents. We analyzed gender differences, and whether the dentists' perceptions of adolescent patients were associated with their professional satisfaction. A stratified random sample of 227 graduates (males = 180, females = 47) from a Southern dental school were asked to complete a questionnaire assessing professional satisfaction. Based on Kruskall-Wallis analysis of variance tests, female dentists expressed generally higher levels of satisfaction than males with adolescent dentistry, diagnosis and treatment planning, patient education, preventive procedures, and the adolescent dentistry curricula during dental school. Male dentists felt that the male adolescents' failure to keep appointments, communication problems, seeking dental care only in emergency situations, and resentment of authority interfered more with their providing adequate dental care than did female dentists. Male dentists also felt that the female patients' menstrual period, communication problems, low tolerance of pain, seeking dental care only in emergency situations, and resentment toward authority were more significant problems than did the female dentists. Communication problems with both male and female adolescents were more strongly correlated with the dentists' satisfaction with adolescent dentistry than any other variable. PMID- 2921188 TI - Breast-feeding attitudes and practices among adolescents. AB - Breast-feeding attitudes of 128 low-income, pregnant adolescents were assessed using a questionnaire developed for this population. Teens who had been breast fed as infants had more positive attitudes than bottle-fed teens (p less than 0.002); no differences in attitudes were found by race or age. Pregnant teens who planned to breast-feed their infants had higher attitude scores than those who planned to bottle feed or who were uncertain (p less than 0.001). Of the sample, 32.4% subsequently breast-fed their baby; these teen mothers had more positive attitude scores than the teen mothers who bottle fed (p less than 0.001). The prenatal infant feeding plans of these pregnant teens were significantly related to their postnatal feeding practices (p less than 0.001). Selected implications of these data for health care professionals are discussed. PMID- 2921190 TI - Intussusception secondary to Meckel's diverticulum. A challenging diagnosis in adolescence. AB - A 14-year-old male was found to have an intussusception secondary to an invaginating Meckel's diverticulum. He was initially referred for crampy abdominal pain and diarrhea, and inflammatory bowel disease was suspected. The etiology of most intussusceptions is unknown; however, both in adolescence and adulthood they may be initiated by a lead point. This paper presents, analyzes, and discusses an intussusception caused by a Meckel's diverticulum as a lead point and the difficulty in making a preoperative diagnosis. PMID- 2921191 TI - An adolescent girl with headache and syncope. AB - A 14-year-old girl with a 3-month history of multiple syncopal episodes followed by headache was diagnosed as having basilar artery migraine. She did not improve on anticonvulsant, anticholinergic, or beta-blocker therapy. Her symptoms resolved during a course of skin temperature biofeedback training, and she remains asymptomatic at 1 year follow-up. PMID- 2921192 TI - Treatment of tetracycline toxicity with tetracycline. PMID- 2921193 TI - Giardiasis--zoonosis or not? PMID- 2921194 TI - Welfare benefits may be taxable. PMID- 2921195 TI - Are veterinarians health professionals? PMID- 2921196 TI - Creative veterinary marketing. PMID- 2921197 TI - Ehrlichiosis. PMID- 2921198 TI - A critical analysis of swine medicine in American veterinary schools. PMID- 2921199 TI - Skillful writing: a tool for today's veterinarian. PMID- 2921200 TI - Goitrogenic effects in offspring of swine fed sulfadimethoxine and ormetoprim in late gestation. AB - Effects of feeding sulfadimethoxine and ormetoprim to sows and gilts in late gestation were evaluated. One sow and 2 gilts were randomly selected and were fed 1 of 3 rations: (1) a gestation ration from farm A, where congenital goiter in newborn pigs was a problem, (2) gestation ration from farm A containing 275 g of sulfadimethoxine and 55 g of ormetoprim/100 kg of ration, or (3) standard swine gestation ration containing 275 g of sulfadimethoxine and 55 g of ormetoprim/100 kg of ration. Sows and gilts were fed the appropriate ration for 22 to 58 days before farrowing. The numbers of stillborn or weak pigs did not increase in any group. However, congenital goiter was detected in all pigs from swine fed medicated rations 2 and 3. Congenital goiter was not present in pigs from swine given gestation ration 1. PMID- 2921201 TI - Radiographic evaluation of nonanesthetized and nonsedated dogs for hip dysplasia. AB - The use of chemical or gas restraint was unnecessary in most large breed dogs being evaluated radiographically for hip dysplasia. Of 100 large-breed dogs, 97 were successfully radiographed for hip dysplasia evaluation without the use of sedation or anesthesia. PMID- 2921202 TI - Diffuse alveolar injury in two dogs. AB - Proliferative interstitial pneumonia of undetermined cause was diagnosed in 2 dogs. The clinical signs in both dogs consisted primarily of acute onset, rapid breathing, and raspy lung sounds. Radiography revealed a diffuse increase in pulmonary alveolar density. In both dogs, the primary pathologic process was diffuse alveolar pneumocyte injury, and the pulmonary lesions were similar. Proliferation of type II pneumocytes (some of which were atypical mononucleated, and others multinucleated) was a prominent feature of the interstitial pneumonia. Because of the atypical features of some pneumocytes in such cases, biopsy findings may suggest a neoplastic process. Proliferative interstitial pneumonia should be included in the differential diagnosis of a diffuse pulmonary disease that is poorly responsive to medical treatment. PMID- 2921203 TI - Anti-triiodothyronine antibodies associated with hypothyroidism and lymphocytic thyroiditis in a dog. AB - A 5-year-old spayed Shetland Sheepdog had clinical signs consistent with hypothyroidism. Laboratory findings, including subnormal serum T4 concentration, also were suggestive of hypothyroidism; however, the apparent serum T3 concentration, as determined by a solid phase assay, was extremely high. Thyroid scintigraphy revealed ectopic radionuclide uptake in the neck and thyroid biopsy revealed lymphocytic thyroiditis. Determination of T3 autoantibody titer confirmed that the previously measured high serum T3 concentration was spuriously high because of autoantibodies to T3. PMID- 2921204 TI - Repair of sixth lumbar vertebral fracture-luxations, using transilial pins and plastic spinous-process plates in six dogs. AB - Transilial pins and paired plastic spinous-process plates were used to repair fracture-luxations of the sixth lumbar vertebra in 6 dogs. All dogs had signs of lumbar pain and variable lower motor neuron deficits to the hindquarters (including hind limbs, tail, and pelvic region). Lumbar pain was decreased or resolved the day after surgery in all dogs, and 3 dogs were able to walk without assistance. One dog initially deteriorated neurologically after surgery and 2 dogs with multiple concurrent orthopedic injuries had no improvement in neurologic function and remained nonambulatory. Pin migration associated with improper bending of the transilial pins and requiring early implant removal was the most common postoperative complication. Four dogs had no neurologic abnormalities 1 to 3 months after surgery. One dog had a resolving unilateral sciatic nerve deficit 9 months after surgery, and another dog was euthanatized 3 months after surgery because of continued paraparesis and urinary and fecal incontinence. These 6 cases illustrate the efficacy of plastic spinous-process plates in combination with transilial pins for the repair of fracture-luxation of the sixth lumbar vertebra. PMID- 2921205 TI - Dinoseb toxicosis in two dogs. AB - Two male English Setters were noticed to be breathing rapidly, hyperexcitable, and atactic after roaming a rural area for 2 hours. Both dogs' cost were stained with yellow liquid. One dog died while en route to the veterinarian. Treatment was begun for the surviving dog for what was initially diagnosed to be organophosphorus or carbamate insecticide toxicosis. Before the diagnosis could be confirmed, the second dog died. The yellow liquid on the dogs' skin was identified as dinoseb in high concentrations. Dinoseb is an acutely toxic, substituted dinitrophenolic herbicide believed to act as an uncoupler of electron transport from oxidative phosphorylation. PMID- 2921206 TI - Pemphigus foliaceus in two Shetland sheepdog littermates. AB - Two female Shetland Sheepdog littermates simultaneously developed pemphigus foliaceus at 6 months of age. Three other littermates were not affected. One bitch (tricolored) was not treated, and the disease has remained active for 2 years. The other bitch (blue merle) has been successfully managed with glucocorticoids and gold salts. PMID- 2921207 TI - Surgical correction of congenital medial patellar luxation in a llama. AB - Unilateral congenital medial patellar luxation in a young llama was corrected by medial joint capsule release, tibial crest transposition, trochleoplasty, and lateral joint capsule imbrication. The techniques used were the same as described in the dog. One year after surgery, the llama was not lame, but had a valgus deformity originating at the stifle, most likely caused by lateral femoral condyle hypoplasia. PMID- 2921208 TI - Cutaneous ergotism in a herd of dairy calves. AB - Weather conditions in northern Illinois favored infection of pasture grasses with Claviceps purpurea. A herd of 52 Holstein heifers selectively grazed the seedheads of an orchard grassbromegrass pasture infected with C purpurea and were poisoned. Peptide alkaloids were found in the sclerotia. Clinical signs of intoxication included lameness, edema of the hind limbs, epilation, areas of skin necrosis, and diarrhea. Pathologic findings included myopachynsis of arterioles in the deep dermal areas, lungs, kidney, spleen, submucosa of small intestines and cerebral cortex, focal cracks on the hoofs, and multifocal areas of detachment of the hoof wall. Of the 52 heifers, 3 died on the farm, 1 was euthanatized, and 3 were sold. The remaining heifers conceived without difficulty, and subsequent calvings were uncomplicated. PMID- 2921209 TI - Aflatoxicosis in Iowa swine: eight cases (1983-1985). AB - During 1983, 1984, and 1985, aflatoxicosis was diagnosed in 8 Iowa swine herds after the herds were fed corn from the 1983 corn crop. As a result of the diagnosis, the associated environmental conditions, clinical signs of aflatoxicosis, macroscopic and microscopic lesions, aflatoxin concentrations detected in feeds, and management of affected swine were reviewed. Concentrations of aflatoxin in shelled corn and complete feed were as high as 2,020 ng and 1,200 ng of aflatoxin (B1 and B2)/g of feed, respectively. Clinical signs of aflatoxicosis included decreased feed consumption and weight loss. Some pigs died acutely, but death often was preceded by a period of clinical disease. Greater morbidity and mortality were observed in swine herds that consumed greater concentrations of aflatoxin. PMID- 2921210 TI - Idiopathic epilepsy in three gaur (Bos gaurus). AB - Idiopathic epilepsy was diagnosed in 3 gaur in a zoologic park collection during a 3-year period. Seizures were characterized by tonic rigidity of all limbs. Results of serum biochemical analysis, CBC, blood lead analysis, CSF analysis, and necropsy were within normal limits in all gaur. The role of heredity in development of seizures in these gaur is unclear because of limited founder stock of gaur in North America. PMID- 2921212 TI - 1987 incomes of US veterinarians. PMID- 2921211 TI - Abortion, stillbirth, neonatal death, and nutritional myodegeneration in a rabbit breeding colony. AB - Vitamin E deficiency was found to be the cause of reproductive failure and nutritional myodegeneration in a rabbit breeding colony. The diagnosis was based on the low vitamin E concentration of doe liver (5.73 micrograms/g) associated with myodegeneration of tongue, skeletal muscle, and heart and the absence of other abnormal microbiologic and parasitologic findings. Supplementation of the diet with wheat germ oil returned the does' fertility to normal, and abortion, stillbirth, and neonatal death ceased. PMID- 2921213 TI - What is your diagnosis? Chronic osteomyelitis of the right scapula and right femur. PMID- 2921214 TI - Isolation and characterization of new antibiotics resorcinomycins A and B. AB - New antibiotics, resorcinomycins A and B, were isolated from the culture broth of a streptomycete strain identified as Streptoverticillium roseoverticillatum. The antibiotics are water-soluble amphoteric substances, positive to SAKAGUCHI'S reagent. The molecular formulas C14H20N4O5 and C13H18N4O5 for A and B were indicated by elemental analysis and secondary ion MS. The structures of these antibiotics were determined by 1H and 13C NMR spectrometry and some chemical evidences to be N-[(S)-alpha-guanidino-3,5-dihydroxy-4 isopropylphenylacetyl]glyci ne and N-[(S)-alpha-guanidino-3,5-dihydroxy-4 ethylphenylacetyl]-glycine, respectively. PMID- 2921215 TI - A new biological role of sangivamycin; inhibition of protein kinases. AB - During the screening for the inhibitors of protein kinase C (PKC), we found that a streptomycete produced an inhibitor in our bleb-forming assay (Osada et al., J. Antibiotics 41: 925, 1988). The inhibitor was isolated and identified as sangivamycin (4-amino-5-carboxamide-7-(D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine). Biological activity of sangivamycin was compared with that of other 7 deazaadenosine group antibiotics, tubercidin and toyocamycin. Sangivamycin showed a strong inhibitory activity against bleb-formation of K562 cells and PKC. On the other hand, tubercidin and toyocamycin had only weak activities in both assays. This paper deals with a new biological activity of sangivamycin, that of an inhibitor of protein kinases, especially PKC. PMID- 2921216 TI - Serum effect on cellular uptake of spermidine, spergualin, 15-deoxyspergualin, and their metabolites by L5178Y cells. AB - Spergualin (SG) and 15-deoxyspergualin (DSG) were more slowly incorporated into L5178Y cells than spermidine. SG and DSG inhibited carrier-mediated transport of [3H]spermidine competitively with inhibition constants of 0.67 mM and 0.45 mM, respectively. Addition of calf serum stimulated uptake of [3H]spermidine into the cells in a serum concentration-dependent manner. The effect was not observed when horse serum was used in place of calf serum. Preincubation of spermidine in calf serum for 1 hour before addition to cells remarkably decreased cellular incorporation of tritium. Three amine oxidase inhibitors, aminoguanidine, 3 hydroxybenzyloxyamine, and semicarbazide, inhibited stimulation of uptake of [3H]spermidine by calf serum and the decrease of it by preincubation in calf serum. So we propose that cellular incorporation or binding of products generated by oxidation of spermidine by amine oxidase in calf serum was much faster than that of spermidine itself and they were unstable and transformed quickly to unincorporable or non-binding substances if cellular targets were not present. Effect of amine oxidase inhibitors on cytotoxic activity of SG and DSG were determined in low and high concentrations of calf serum. In the presence of 10% calf serum in the basal medium, cytotoxicity to L5178Y cells by SG and DSG was suppressed at high drug concentrations (above 10 micrograms/ml) and enhanced at low drug concentrations (below 2.5 micrograms/ml) by amine oxidase inhibitors. In the presence of 0.5% calf serum suppression of cytotoxicity at high drug concentrations by amine oxidase inhibitors was also observed, but enhancement at low drug concentrations was obscure. These data may suggest the existence of two kinds of cytotoxic mechanism of SG and DSG, one dependent on and one independent of amine oxidase in serum. PMID- 2921217 TI - Structural alteration of SN-07 chromophore. PMID- 2921218 TI - Microbial O-phosphorylation of macrolide antibiotics. PMID- 2921219 TI - Isolation and properties of a blasticidin S acetylating enzyme from a producer organism. PMID- 2921220 TI - A new antibiotic, tautomycetin. PMID- 2921221 TI - A new antitumor antibiotic, FR-66979. PMID- 2921222 TI - Structures of jietacines: unique alpha,beta-unsaturated azoxy antibiotics. PMID- 2921223 TI - Two new carbapenem antibiotic-producing actinomycetes: Kitasatosporia papulosa sp. nov. and Kitasatosporia grisea sp. nov. AB - Two new carbapenem antibiotic-producing actinomycetes, the cell-walls of which contain LL-diaminopimelic acid and meso-diaminopimelic acid, were isolated from soil. The two strains were subjected to taxonomic studies, which involved morphological, cultural, physiological and chemotaxonomical characterization, the latter including the cell-wall chemo-type, whole-cell sugar composition, phospholipid composition, menaquinone system and DNA base composition. These strains were identified as new species of the genus Kitasatosporia. The proposed names are Kitasatosporia papulosa for strain AB-110 (IAM 13637, FERM 9000, JCM 7250) and Kitasatosporia grisea for strain AA-107 (IAM 13638, JCM 7249). PMID- 2921224 TI - Origin of monacolin L from Aspergillus terreus cultures. AB - In freshly harvested Aspergillus terreus cultures grown for the production of lovastatin (formerly called mevinolin), no monacolin L could be detected. However, during the isolation of lovastatin, significant quantities of monacolin L appeared. It has been discovered that a new metabolite structurally related to the members of the monacolin series is present. This metabolite is unstable and under mildly acidic conditions and elevated temperature, it converts to monacolin L. The subject metabolite is proven to be a hydroxylated derivative of dihydromonacolin L identified as 3 alpha-hydroxy-3,5-dihydromonacolin L. It seems that all monacolin L found later during various treatments of the broth and broth extracts is formed from that precursor via a dehydration reaction. The new metabolite was converted to its phenacyl ester, by means of extractive alkylation, for isolation and structure elucidation by chemical, chromatographic and spectroscopic methods. This ester, on standing, gradually formed the corresponding lactone. PMID- 2921225 TI - Endusamycin, a novel polycyclic ether antibiotic produced by a strain of Streptomyces endus subsp. aureus. AB - Endusamycin formerly called CP-63,517 (C47H77O14Na), is a novel polycyclic ether antibiotic produced by a new strain of Streptomyces endus subsp. aureus (ATCC 39574). Recovery, fractionation and purification were achieved using standard procedures. Forms include the endusamycin free acid, mp 95 approximately 105 degrees C, lambda max 232 nm (log E 4.16), [alpha]25D +47.4 degrees (c 0.5, methanol) and a crystalline sodium salt, mp 215 approximately 220 degrees C, lambda max 232 nm, (log E 4.15), [alpha]25D +25 degrees (c 0.5, methanol). The structure is shown below, Fig. 1. Endusamycin exhibited; antibacterial activity, in vitro against Gram-positive and anaerobic bacteria, effectiveness against coccidia in poultry, and stimulation of propionic acid production in an in vitro system. PMID- 2921226 TI - Hydrogenation of quinone compounds during secondary ion mass spectra measurement. AB - Antibiotics containing a quinone group show characteristic reduced pseudo molecular ions (M + 2)+ and (M + 3)+ during the measurements of secondary ion mass spectra using glycerol as a matrix. The ratios of peak intensities (M + 2)+ and (M + 3)+ over (M + 1)+ increase with time. As this phenomenon is not found using sulfolane as a matrix, the quinone group seems to be hydrogenated to a hydroquinone by active hydrogen which is produced from a free hydroxyl group of the glycerol by bombardment with the Xe+ beam. This hydrogenation reaction is specific for the quinone group. PMID- 2921227 TI - Synthesis and structure-activity relationships of 3-(2-imidazolyl)thiomethyl cephalosporins. AB - The synthesis and structure-activity relationships of a series of 3-(2 imidazolyl)thiomethyl cephalosporins are described. Among the compounds, 7 beta [2-(2-amino-1,3-thiazol-4-yl)-(Z)-2-methoxyiminoacetamido]-3- [(4,5 dicarboxyimidazol-2-yl)thiomethyl]-3-cephem-4-carboxylic acid (1) exhibited potent activity against both Gram-positive and Gram-negative bacteria including Pseudomonas aeruginosa. We also estimated lipophilicity of the compounds from the chromatographic log k' value of reversed-phase HPLC. The relationship between lipophilicity and biological activity showed that compound 1 had the most suitable lipophilicity. PMID- 2921229 TI - Viriplanin A, a new anthracycline antibiotic of the nogalamycin group. II. The structure of a novel hydroxyamino sugar from reduced viriplanin A. AB - Methyl 2,3,6-trideoxy-3-hydroxyamino-3-C-methyl-alpha-D-ribo-hexopyranoside+ ++ (2) and the corresponding amino sugar (4) were isolated from reduced viriplanin A by acidic methanolysis and esterified to the di-p-bromobenzoates (3 and 5), respectively. The absolute configuration of crystalline 3 was determined by X-ray analysis to be alpha-D. This result could be confirmed by oxidation of 2 to methyl alpha-D-decilonitroside (6) and from the CD spectra of 3 and 5. Thus, the nitrogen-containing sugars of viriplanin A and probably those of decilorubicin and arugomycin belong to the D-series. PMID- 2921228 TI - Synthesis and antibacterial evaluation of N-alkyl vancomycins. AB - Over eighty N-alkyl vancomycins were synthesized by reductive alkylation of vancomycin with the appropriate aldehydes. The N-alkyl vancomycins exhibit greater antibacterial activity than the corresponding N-acyl vancomycins and the parent antibiotic. Some of these semisynthetic vancomycins are five times more active than vancomycin. The N-alkyl vancomycins also show longer elimination half lives in rats than vancomycin. PMID- 2921230 TI - Phenelfamycins, a novel complex of elfamycin-type antibiotics. III. Activity in vitro and in a hamster colitis model. AB - Phenelfamycins A, B, C, E, F and unphenelfamycin make up a recently isolated group of elfamycin-type antibiotics. All of the phenelfamycins were active against Gram-positive anaerobes, including Clostridium difficile. Phenelfamycin A was also active in vitro against Neisseria gonorrhoeae and Streptococci. Phenelfamycin A was found to be effective in prolonging the survival of hamsters in an animal model of C. difficile enterocolitis. After oral administration of phenelfamycin A to hamsters, antibiotic was detected in the caecal contents but not in the blood. PMID- 2921231 TI - Rat pituitary tumor cells in serum-free culture. I. Selection of thyroid hormone responsive and autonomous cells. AB - The growth of GH4C1, GH3, GH1, and GH3C15 rat pituitary tumor cell lines was studied in a serum-free medium (designated TRM-1) formulated with 1:1 (vol/vol) mixture of Ham's F12 nutrient mixture and Dulbecco's modified Eagle's medium (F12 DME) containing 15 mM 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES), 50 micrograms/ml gentamicin supplemented with 10 micrograms/ml bovine insulin, 10 micrograms/ml human transferrin (Tf), 10 ng/ml selenous acid, 10 nM 3,5,3' triiodothyronine (T3), 50 microM ethanolamine (Etn), and 500 micrograms/ml bovine serum albumin. Of the lines evaluated, only the GH1 failed to grow in TRM-1. Passage of the GH4C1 and GH3 lines from serum-containing medium into TRM-1 caused an initial selection resulting in cells that grew progressively at higher rates and finally were maintained indefinitely in TRM-1. These populations showed a requirement for supraphysiologic concentrations of T3 (1.0 to 10 nM). After adaptation of the GH4C1 line in TRM-1 for greater than or equal to 20 generations, removal of components gave a less complex mixture containing 15 mM HEPES, 50 micrograms/ml gentamicin, 10 micrograms/ml Tf, 10 nM T3, and 50 microM Etn (designated TRM-2) that supported serial passage of the cells. Under these conditions, thyroid hormone dependence was lost progressively. When T3 was removed from TRM-2 adapted cells, a third population was selected that no longer required thyroid hormones and was only slightly stimulated by T3. These studies demonstrated that the combination of serum-containing and serum-free conditions can be used to select pituitary cell populations that a) required both serum factor(s) and T3 for optimum growth, b) required supraphysiologic concentrations of T3 without serum proteins other than Tf and albumin, and c) were completely autonomous in that they proliferated in medium supplemented only with Tf and nutrients without necessity of other serum factor(s) or T3. PMID- 2921232 TI - Rat pituitary tumor cells in serum-free culture. II. Serum factor and thyroid hormone requirements for estrogen-responsive growth. AB - The effect of 17 beta-estradiol (E2) on growth of GH4C1 rat pituitary tumor cells was investigated under serum-free conditions and with medium containing charcoal extracted serum. Serum-free TRM-1 medium was a 1:1 (vol/vol) mixture of F12-DME supplemented with 50 micrograms/ml gentamicin, 15 mM 4-(2-hydroxyethyl)-1 piperazineethanesulfonic acid, 10 micrograms/ml insulin, 10 micrograms/ml transferrin, 10 ng/ml selenous acid, 10 nM 3,5,3'-triiodothyronine (T3), 50 microM ethanolamine, and 500 micrograms/ml bovine serum albumin. The cells grew continuously in TRM-1 but were E2 responsive only when growth was retarded by reducing the T3 concentration to 10 pM (TRM-MOD). Addition of 1 to 10 nM E2 to TRM-MOD increased growth by 0.3 to 0.9 cell population doublings over controls in 9 d. By using medium supplemented with charcoal-extracted sera, basal growth became 1 to 1.5 cell population doublings in 9 d. Addition of 0.1 pM E2 to medium containing charcoal-extracted serum caused a significant increase in cell number whereas pM-nM concentrations stimulated 200 to 570% increases over controls. The effect of steroid hormone was the same in phenol-red-containing and indicator free medium. The data presented confirm that the major requirements for demonstration of estrogenic effects in culture were optimum concentrations of thyroid hormones and the presence of yet-to-be-characterized serum factors. PMID- 2921233 TI - Growth of rat mammary tumor line 64-24 in liposome-supplemented defined medium. I. Effect of liposome B components on colony growth. AB - An improved serum-free medium has been developed that supports growth of rat mammary tumor line 64-24 with far less protein supplementation and with a much smaller inoculum than previously possible. An initial survey showed that MCDB 202 supported clonal growth with 1% dialyzed serum. The remaining serum was then replaced with 5 micrograms/ml insulin, 10 ng/ml epidermal growth factor (EGF), 1 micrograms/ml hydrocortisone, 50 ng/ml ovine prolactin, and 5 micrograms/ml liposome B (a mixture of soy lecithin, sphingomyelin, cholesterol, vitamin E, and vitamin E acetate in liposome form). Insulin and EGF are required and growth is improved by hydrocortisone and prolactin. Estradiol is stimulatory in the absence of liposome B. With adequate iron supplementation, transferrin has no effect. Liposome B increases growth rate substantially. Most of the growth stimulation can be replaced with phosphatidylethanolamine or sphingomyelin. PMID- 2921234 TI - Growth of rat mammary tumor line 64-24 in liposome-supplemented defined medium. II. Effect of liposome B and prolactin on colony forming efficiency. AB - During studies on serum-free clonal growth of rat mammary tumor line 64-24, we observed that liposome B causes a major increase in colony-forming efficiency. This phenomenon was studied with a short-term assay based on phase contrast microscopic observation of the effects of liposome B on recently plated, serum depleted cells. In the serum-free medium, colony forming efficiency is not determined primarily by viability (measured by dye exclusion) or cell attachment. Instead, most of the effect is determined by the extent of degeneration that occurs during cell elongation and the first division. Factors that prevent degeneration, such as liposome B, restore colony forming efficiency. Prolactin alone stimulates cell elongation but does not prevent degeneration. However, the combination of prolactin and liposome B increases colony formation to levels observed in the presence of serum. PMID- 2921235 TI - Analysis of plasma protein and lipoprotein synthesis in long-term primary cultures of baboon hepatocytes maintained in serum-free medium. AB - The analysis of lipoprotein synthesis and secretion in primary hepatocytes has been restricted by the short-term viability and low proliferative response of hepatocytes in vitro. During this investigation a serum-free medium formulation was developed that supports long-term maintenance (greater than 70 d) and active proliferation of primary baboon hepatocytes. Examination of proliferating cells by electron microscopy revealed a distinctive hepatocyte ultrastructure including intercellular bile canaliculi and numerous surface microvilli. High levels of secreted apolipoproteins A-I and E were detected in the tissue culture medium by gel electrophoresis and immunoblot analysis. Immunoprecipitation of proteins from [35S]-methionine labeled tissue culture medium revealed the synthesis and secretion of numerous plasma proteins. Metabolic labeling of cells with [35S] methionine followed by single-spin density gradient flotation of the media demonstrated that apolipoproteins were being secreted in the form of lipoprotein particles with buoyant densities corresponding to the very low density lipoprotein and low density lipoprotein range, and to the high density lipoprotein range. The labeled apolipoproteins included Bh, E, and A-I. This system for primary hepatocyte culture should prove very useful in future investigations on the regulation of lipoprotein production by hepatocytes. PMID- 2921236 TI - Characterization of vascular smooth muscle cell phenotype in long-term culture. AB - Studies of bovine carotid artery smooth muscle cells, during long-term in vitro subcultivation (up to 100 population doublings), have revealed phenotypic heterogeneity among cells, as characterized by differences in proliferative behavior, cell morphology, and contractile-cytoskeletal protein profiles. In vivo, smooth muscle cells were spindle-shaped and expressed desmin and alpha smooth muscle actin (50% of total actin) as their predominant cytoskeletal and contractile proteins. Within 24 h of culture, vimentin rather than desmin was the predominant intermediate filament protein, with little change in alpha-actin content. Upon initial subcultivation, all cells were flattened and fibroblastic in appearance with a concomitant fivefold reduction in alpha-actin content, whereas the beta and gamma nonmuscle actins predominated. In three out of four cell lines studied, fluctuations in proliferative activity were observed during the life span of the culture. These spontaneous fluctuations in proliferation were accompanied by coordinated changes in morphology and contractile cytoskeletal protein profiles. During periods of enhanced proliferation a significant proportion of cells reverted to their original spindle-shaped morphology with a simultaneous increase in alpha-actin content (20 to 30% of total actin). These results suggest that in long-term culture smooth muscle cells undergo spontaneous modulations in cell phenotype and may serve as a useful model for studying the regulation of intracellular protein expression. PMID- 2921237 TI - Stainless steel mesh supports high density cell growth and production of recombinant mullerian inhibiting substances. AB - Stainless steel mesh supported the high density growth of anchorage dependent CHO fibroblasts without the use of a special culture system. CHO cells, designated B 9, containing an amplified genomic construct of the human gene for Mullerian Inhibiting Substance (MIS), grew to a high confluent density on stainless steel meshwork while producing substantial amounts of human recombinant MIS over a long period of time. The mesh could be easily coated with various extracellular matrix proteins, such as Laminin, Fibronectin, Collagen or Matrigel, which permitted the testing of the effects of surface modifications on cell yield and recombinant protein production. Since the amount of medium per surface area required for optimal cell growth is lower than for some large volume cell culture methods, media costs can be reduced using mesh. In addition, no special cell culture equipment or complex manipulations are required. Thus, the use of meshwork for anchorage-dependent cells can increase the efficiency of growth and decrease the cost of recombinant protein production. PMID- 2921238 TI - Two transcribing activities are involved in expression of the Streptomyces galactose operon. AB - The Streptomyces galactose operon is transcribed from two independently regulated promoters: galP1, located at the 5' end of the operon and responsible for galactose-dependent transcription of the operon, and galP2, an internal constitutive promoter. We identified and partially separated two distinct transcribing activities involved in expression of this operon. Using RNA polymerase from Streptomyces lividans and Streptomyces coelicolor partially purified by chromatography on heparin-agarose and DNA-cellulose, we detected activities capable of initiating transcription in vitro specifically from either galP1 or galP2. Circumstantial evidence suggests that the activity for galP2 transcription is a holoenzyme species associated with the previously described sigma 28 protein (referred to here as sigma C). The galP1-transcribing activity is more difficult to evaluate. This activity may correspond to a holoenzyme species associated with sigma A (formerly sigma 35), although other possibilities are discussed. This would be the second reported example of a catabolite controlled gene in Streptomyces species expressed from multiple promoters recognized by different holoenzyme forms. This may indicate that the involvement of RNA polymerase heterogeneity in gene expression in Streptomyces species is a more general strategy for regulation than the specialized gene expression seen in Escherichia coli. PMID- 2921239 TI - Activation of formylmethanofuran synthesis in cell extracts of Methanobacterium thermoautotrophicum. AB - In cell extracts of Methanobacterium thermoautotrophicum, formylmethanofuran (formyl-MFR) synthesis (an essential CO2 fixation reaction that is an early step in CO2 reduction to methane) is subject to a complex activation that involves a heterodisulfide of coenzyme M and N-(7-mercaptoheptanoyl)threonine O3-phosphate (CoM-S-S-HTP). In this paper we report that titanium(III) citrate, a low potential reducing agent, stimulated CO2 reduction to methane and activated formyl-MFR synthesis in cell extracts. Titanium(III) citrate functioned as the sole source of electrons for formyl-MFR synthesis and enabled this reaction to occur independently of CoM-S-S-HTP. In addition, CoM-S-S-HTP was found to activate an unknown electron carrier that reduced metronidazole. The activation of formyl-MFR synthesis by CoM-S-S-HTP may involve the activation of a low potential electron carrier. PMID- 2921240 TI - Microbial degradation of beta-chlorinated four-carbon aliphatic acids. AB - Alcaligenes sp. strain CC1 is able to grow on several alpha-chlorinated aliphatic acids (2-chlorobutyrate, 2-chloropropionate, and chloroacetate), as well as on the beta-chlorinated four-carbon aliphatic acids trans-3-chlorocrotonate, cis-3 chlorocrotonate, and 3-chlorobutyrate as sole carbon and energy sources. Dehalogenation of alpha-chlorinated acids could be measured by using resting cells grown on all the different carbon sources, whereas dehalogenation of beta chlorinated four-carbon acids could be detected only by using resting cells grown on four-carbon compounds. A constitutive 2-haloacid dehalogenase, which did not show any activity with beta-chlorinated four-carbon acids, was detected in cell extracts. Cell extracts of crotonate-grown cells additionally contained a beta haloacid dechlorination activity, which acted on trans-3-chlorocrotonate, cis-3 chlorocrotonate, and 3-chlorobutyrate and was strictly dependent on coenzyme A, ATP, and Mg2+. Dechlorination of beta-chlorinated four-carbon acids takes place after activation of the acids to their coenzyme A derivatives and seems to be independent of the constitutive 2-haloacid dehalogenase. PMID- 2921241 TI - Identification and sequence analysis of two related flagellin genes in Rhizobium meliloti. AB - The genomic region that codes for the flagellin subunits of the complex flagellar filaments of Rhizobium meliloti was cloned and sequenced. Two structural genes, flaA and flaB, that encode 395- and 396-amino-acid polypeptides, respectively, were identified. These exhibit 87% sequence identity. The amino acid sequences of tryptic peptides suggest that both of these subunit proteins are represented in the flagellar filaments. The N-terminal methionine was absent from the mature flagellin subunits. Their derived primary structures show almost no relationship to flagellins from Escherichia coli, Salmonella typhimurium, or Bacillus subtilis but exhibit up to 60% similarity to the N- and C-terminal portions of flagellin from Caulobacter crescentus. It is suggested that the complex flagellar filaments of R. meliloti are unique in being assembled from heterodimers of two related flagellin subunits. The tandemly arranged flagellin genes were shown to be transcribed separately from unusual promoter sequences. PMID- 2921242 TI - Identification and characterization of catA, a mutation causing catalase deficiency in Dictyostelium discoideum. AB - Various strains of Dictyostelium discoideum were assayed for catalase activity. We were able to demonstrate the presence of catalase in lysates of all strains tested except one, ts12m. Lysates of this strain did not show any detectable level of catalase. The increased sensitivity of intact ts12m amoebae to hydrogen peroxide was consistent with the catalase deficiency. We followed catalase activity through a developmental time course for the wild type (Ddb) and were able to show its presence throughout development. No catalase activity was detected from ts12m in any stage of development. The growth and development of this acatalasemic strain of D. discoideum was no different than those of the wild type. The mutation, catA, was assigned to linkage group II. PMID- 2921243 TI - Changes in diadenosine tetraphosphate levels in Physarum polycephalum with different oxygen concentrations. AB - Cellular levels of diadenosine tetraphosphate (Ap4A) were measured, by a specific high-pressure liquid chromatography method, in microplasmodia of Physarum polycephalum subjected to different degrees of hypoxia, hyperoxia, and treatment with H2O2. Ap4A levels increased three- to sevenfold under anaerobic conditions, and the microplasmodia remained viable after such treatment. Elevated levels of Ap4A returned to the basal level within 5 to 10 min upon reoxygenation of the microplasmodia. The increases in Ap4A levels were larger in stationary-phase or starved microplasmodia than in fed, log-phase microplasmodia. The maximal increase measured in log-phase microplasmodia was twofold. No significant changes in Ap4A levels occurred in microplasmodia subjected to mild hypoxia, hyperoxia, or treatment with 1 mM H2O2. These results indicate that in P. polycephalum, Ap4A may function in the metabolic response to anaerobic conditions rather than in the response to oxidative stress. PMID- 2921244 TI - Organization of the flaFG gene cluster and identification of two additional genes involved in flagellum biogenesis in Caulobacter crescentus. AB - In Caulobacter crescentus, mutations have been isolated in more than 30 flagellar genes (fla, flb, and flg) which are required in the cell cycle event of flagellum biogenesis. The flaF and flaG mutations and two newly identified mutations, flbT and flbA (P.V. Schoenlein and B. Ely, J. Bacteriol. 171:000-000, 1989), have been localized to the flaFG region. In this study, the genetic and physical organization of this region was analyzed, using the cloned 4.0-kilobase flaFG region in the recombinant plasmid pPLG727. Plasmid pPLG727 complemented flaF, flaG, flbA, and flbT mutations. Further complementation studies with pPLG727 derivatives indicated that flaF and flbT are unique but overlapping transcription units, whereas flbA and flaG constitute a single transcription unit. To determine the direction of transcription of the putative flbA-flaG operon, the promoterless chloramphenicol transacetylase gene was inserted into various positions in the flbA-flaG region, and merodiploid strains containing these transcriptional fusions were assayed for gene function and expression of chloramphenicol resistance. These studies showed that transcription proceeds from flbA to flaG. To confirm the complementation analysis, Southern analyses were performed on chromosomal DNAs isolated from strains containing insertion and deletion mutations. Taken together, these studies defined the relative gene order at one end of the flaYG flagellar gene cluser as flgL-flaF-flbT-flbA-flaG. PMID- 2921245 TI - Role for [corrected] Agrobacterium tumefaciens ChvA protein in export of beta-1,2 glucan. AB - Functional chvA and chvB genes are required for attachment of Agrobacterium tumefaciens to plant cells, an early step in crown gall tumor formation. Strains defective in these loci do not secrete normal amounts of cyclic beta-1,2-glucan. Whereas chvB is required for beta-1,2-glucan synthesis, the role of chvA in glucan synthesis or export has not been clearly defined. We found that cultures of chvA mutants contained as much neutral beta-1,2-glucan in the cell pellets as did the wild type, with no detectable accumulation of glucan in the culture supernatant. The cytoplasm of chvA mutant cells contained over three times more soluble beta-1,2-glucan than did the cytoplasm of the wild-type parent. Unlike the wild type, chvA mutants contained no detectable periplasmic glucan. The amino acid sequence of chvA is highly homologous to the sequences of bacterial and eucaryotic export proteins, as observed previously in the case of ndvA, a rhizobial homolog of chvA. Strong sequence homology within this family of export proteins is concentrated in the carboxy-terminal portions of the proteins, but placement of consensus ATP-binding sites, internal signal sequences, and hydrophobic domains are conserved over their entire lengths. These data suggest a model for beta-1,2-glucan synthesis in A. tumefaciens in which glucan is synthesized inside the inner membrane with the participation of ChvB and transported across the inner membrane with the participation of ChvA. PMID- 2921246 TI - A protein required for transcriptional regulation of Agrobacterium virulence genes spans the cytoplasmic membrane. AB - The VirA protein is one of two proteins required for transcriptional activation of Agrobacterium tumefaciens virulence genes in response to phenolic compounds released by plants during infection. We describe two experimental approaches which indicate that this protein has a transmembrane topology. First, spheroplasts of Escherichia coli or wild-type A. tumefaciens expressing the VirA protein were treated with proteinase K to digest periplasmic proteins, and the remaining proteins were immunologically stained on Western blots (immunoblots) by using anti-VirA antibody. Second, transposon TnphoA was used to generate translational fusions between virA and phoA, the latter of which is the structural gene for alkaline phosphatase. Both techniques indicated that VirA spans the cytoplasmic membrane, with approximately 275 amino acids near the amino terminus being localized in the periplasmic space and the rest of the protein being localized in the cytoplasm. We also show that overexpression of VirA in E. coli is deleterious to cell growth and that this phenomenon depends on the synthesis of either the second hydrophobic core or some nearby portion of the VirA protein. PMID- 2921247 TI - Cloning and sequence analysis of flaA, a gene encoding a Spirochaeta aurantia flagellar filament surface antigen. AB - Spirochaeta aurantia DNA that coded for an antigenic determinant of the flagellin associated with the filament surface of the periplasmic flagella was isolated. When expressed in Escherichia coli, the antigenic polypeptide had an apparent molecular weight of 37,000. Sequence analysis of the antigen-encoding DNA revealed the presence of an open reading frame that determined a polypeptide with a predicted molecular weight of 31,241. This polypeptide showed a region of identity with the N-amino-terminal region of the 39,000- and 37,000-dalton flagellins of the distantly related spirochetes Treponema phagedenis and Treponema pallidum, respectively (S. J. Norris, N. W. Charon, R. G. Cook, M. D. Fuentes, and R. J. Limberger, J. Bacteriol. 170:4072-4082, 1988). The region of identity in the deduced S. aurantia polypeptide was preceded by a possible signal sequence and signal peptidase cleavage site. PMID- 2921248 TI - Mutation of Bacillus firmus OF4 to duramycin resistance results in substantial replacement of membrane lipid phosphatidylethanolamine by its plasmalogen form. AB - Mutant strains of alkalophilic Bacillus firmus OF4 that were selected for resistance to duramycin had greatly reduced levels of membrane diacylphosphatidylethanolamine, as had been found in studies of such mutants of Bacillus subtilis. In the B. firmus strains, however, substantial levels of plasmenylethanolamine were found. This is an unusual membrane component for an aerobic eubacterium, but the presence of trace amounts even in the wild type was confirmed in experiments with 32Pi-labeled growth medium. The membrane lipid composition of the duramycin-resistant strains had several other changes that also left alkalophilic growth unimpaired. PMID- 2921250 TI - Structure of an acidic exopolysaccharide of Pseudomonas marginalis HT041B. AB - The exopolysaccharide of Pseudomonas marginalis HT041B has been characterized as a 1,3-linked galactoglucan in which galactose and glucose are in the alpha- and beta-anomeric configurations, respectively. The polysaccharide is substituted with pyruvate at the 4 and 6 positions of galactose and with succinic acid at either the 2 or 4 position of glucose. This polysaccharide has been given the trivial name marginalan. PMID- 2921249 TI - Two chromosomal loci involved in production of exopolysaccharide in Agrobacterium tumefaciens. AB - The chromosomal locus pscA (exoC) of Agrobacterium tumefaciens LBA4301 has been cloned by complementation of the avirulent and exopolysaccharide (EPS)-deficient mutant LBA4301 pscA. We have also identified a new locus, termed psdA (polysaccharide depression) and located 16 kilobases from pscA in the A. tumefaciens chromosome, that negatively affects EPS production when it is present in more than one copy in A. tumefaciens LBA4301. Subcloning, transposon mutagenesis, and transcriptional analysis have been conducted for both loci and indicate that pscA and psdA are transcribed in the same orientation. Acidic-EPS assays showed that psdA depresses succinoglycan production and that its negative effect increases with the copy number of the gene. Virulence tests of psdA transconjugants on Datura stramonium showed no visible alteration in virulence, while LBA4301 pscA was totally avirulent. PMID- 2921251 TI - Immunity to diphtheria, six to 15 years after a basic three-dose immunization schedule. AB - The results of a study of the immunity to diphtheria of 283 girls (9-18 years of age) vaccinated at the age of two years with three doses of vaccine, are reported. The rabbit skin test was used to determine the titre of serum diphtheria antitoxin. 55.8% of the subjects were found to be protected (titre greater than or equal to 0.1 IU/ml), 38.9% were only relatively immune (titre greater than or equal to 0.01- less than 0.01 IU/ml), and 5.3% were unprotected (titre less than 0.01 IU/ml). The antitoxin titres showed a tendency to decrease with time. Even so, 6-15 years after vaccination, the percentages of protected and partially protected subjects were still high (95%). PMID- 2921252 TI - A comparison of polyclonal antisera to pregnanediol 3 alpha glucuronide obtained from three different rabbits and their use in ELISA. AB - The variation in the estimates of urinary pregnanediol glucuronide obtained by ELISA with 12 polyclonal antisera has been assessed. Of the 12 antisera, eight gave values comparable with each other and could be used interchangeably in the ELISA. Thus a large stock of polyclonal antibody which gave consistent values was generated and can now be used in diagnostic ELISA over a long period of time. This procedure is more economical than the development of monoclonal antibodies for the same purpose. PMID- 2921253 TI - The quantitative assay of the clustering activity of the lymphocytosis-promoting factor (pertussis toxin) of Bordetella pertussis on Chinese hamster ovary (CHO) cells. AB - An experimental design and a statistical method for the estimation of the clustering-response activity of lymphocytosis-promoting factor (LPF) in Chinese hamster ovary cells growing in wells on a microplate were investigated. The scoring method introduced by Ipsen was adopted to express the grade of the clustering response rather than the end-point method generally used. The scoring method was validated by statistical analyses. The grade of response varied with the location of the wells on a microplate, and thus the expression of the clustering activity of a test sample in terms of the end-point may be inadequate in terms of accuracy and reproducibility. It was shown that the allocation of test samples to individual wells according to a Latin square design minimized the effect of the location of wells on the clustering response. Under such experimental conditions, a fairly precise and reproducible method for the quantification of the clustering activity was developed. PMID- 2921254 TI - Actual burn nutrition care practices. A national survey (Part I). PMID- 2921255 TI - A randomized trial of plasma exchange in the treatment of burn shock. AB - Hypovolemia following major thermal injury results from increased capillary permeability with subsequent loss of fluid into the interstitium. Investigations of burn shock have demonstrated the release of circulating factors that effect these fluid shifts. Previous studies have suggested that this process can be altered by the performance of plasma exchange in patients who fail to respond to conventional resuscitation. This study evaluated the effect of plasma exchange during burn shock. Twenty-two adult subjects were randomly assigned to one of two groups. The control group received standard fluid resuscitation guided by the Parkland formula; the treatment group received the same resuscitation in addition to a course of plasma exchange. Seventeen subjects, eight from the control group and nine from the plasma exchange group, completed the study. Control subjects had a mean age of 37 years, a mean burn size of 52.3% total body surface area, and a mean full-thickness injury of 24.6% total body surface area. Plasma exchange patients had a mean age of 38 years, a mean burn size of 49.4% total body surface area, and a mean full-thickness injury of 37.3% total body surface area (p less than 0.01 compared to the control group). Completion of resuscitation was accomplished earlier in the plasma exchange group (20.2 hours versus 30.8 hours; p less than 0.05). There was no difference in the total amount of fluid required to achieve resuscitation. The mean urine output during resuscitation was greater for the plasma exchange group (p less than 0.01). Performance of plasma exchange during the second 8-hour period after the burn did not alter the course of burn shock in this study group. PMID- 2921256 TI - Sequence of morphologic events in experimental smoke inhalation. AB - The experimentally induced smoke inhalation injury in sheep is in many respects similar to that observed in smoke-injured humans. Our sheep model allows us to describe a sequence of morphologic changes that may be divided into four fairly discrete although overlapping phases. The magnitude of the destructive process and the length and characteristics of each phase are related to the severity of the injury and the superimposed complications. The availability of this animal model may allow the experimental manipulation of each of the four described phases to investigate physiopathologic and therapeutic implications toward the prompt normalization of pulmonary function. PMID- 2921257 TI - Normal phosphatidylcholine composition of lung surfactant 24 hours after inhalation injury. AB - The effects of cotton smoke injury on the phosphatidylcholine composition of pulmonary surfactant material were studied. While under halothane anesthesia, 18 ewes were intubated using a double-lumen tube. In six sheep the left lung was exposed to smoke; in another six sheep the right lung was exposed to smoke. A sham group of six sheep was insufflated with air instead of smoke. Twenty-four hours later the animals were killed, and alveolar lavage fluid was obtained from both lungs. Phospholipid material was separated, and its relative phosphatidylcholine composition was determined. In the smoke-treated lungs this composition was not different statistically when compared with the contralateral and the sham-exposed lungs. These findings suggested that smoke inhalation has no effect on the composition of the phosphatidylcholine fraction in the alveolar lining layer 24 hours after injury. PMID- 2921258 TI - Effects of inhalation injury on airway blood flow and edema formation. AB - We measured airway blood flow in unanesthetized sheep under control conditions and after lung injury induced by inhalation of cotton smoke. Blood flows in trachea, carina, main stem bronchi, intraparenchymal bronchi, and whole lung were measured by injection of radioactive microspheres. In 10 control sheep mean blood flow (+/- SD) was trachea, 17.2 +/- 10.5; main stem bronchi, 17.5 +/- 7.6; and whole lung (parenchyma inclusive of all small intraparenchymal airways), 20.5 +/- 11.9 ml.min-1/100 gm tissue weight. After injury, measurements were made 8 to 30 hours after smoke inhalation when respiratory distress was evident by arterial oxygen tensions of less than 60 mm Hg. Inhalation injury had little effect on cardiac output or blood flow to peripheral tissue. However, after inhalation injury airway blood flow (n = 6) was increased nine times in trachea, eight times in main stem bronchi, twelve times in intraparenchymal bronchi, and two times in whole lung. The increased airway blood flow resulted from a selective vasodilation of the airway vasculature because arterial driving pressures were unchanged by inhalation injury. Other investigators have shown that the microvascular permeability of the bronchial circulation is remarkably sensitive to inflammation, and the present experiments suggest that a selective vasodilation of the airway vasculature is another aspect of the airway response to inflammation. Increased airway blood flow through a leaky microvasculature may increase capillary filtrate from the bronchial circulation and contribute to the pulmonary edema of inhalation injury. PMID- 2921259 TI - Smoke inhalation and airway management at a regional burn unit: 1974-1983. Part I: Diagnosis and consequences of smoke inhalation. AB - Victims of smoke inhalation with and without burns and burn patients with respiratory insufficiency for reasons other than smoke at a regional burn unit are profiled in terms of age, burn size, length of stay, and mortality. The diagnostic characteristics of patients with an inhalation injury (N = 108) are listed; 7% of all patients (N = 52) have known smoke exposure with equivocal evidence for injury to the airway or pulmonary parenchyma. The degree of respiratory (visceral) failure experienced by patients with inhalation injury is not uniformly severe. Many of the clues to this diagnosis are indirect and not always related to the severity of pulmonary injury. Timing and degree of visceral failure control the severity of the injury, which increases progressively from that in patients with a burn only (parietal injury) through those with a visceral injury only (smoke without burn), those with both smoke and burn, to those with a burn and uniformly severe respiratory failure on the basis of sepsis. PMID- 2921260 TI - Topical lidocaine in the treatment of partial-thickness burns. AB - The analgesic properties and systemic absorption of topical lidocaine in the treatment of partial-thickness burns were evaluated by applying a 5% lidocaine cream to the burn wound at a concentration of 1 mg/cm2. The plasma lidocaine level was measured in 24 patients 15, 30, 60, 120, and 240 minutes after application. Systemic analgesics were given 30 minutes before application of the lidocaine cream. The Visual Analog Scale was used to record pain intensity in 30 patients just before and 30 minutes after application of the lidocaine cream. The maximal area treated was 28% total body surface area partial-thickness burn with application of 4.5 gm of lidocaine, resulting in a plasma level of 5.8 micrograms/ml. The plasma lidocaine level was constant during the 4-hour experiment and was associated with a significant decrease in pain. No infectious, allergic, or cardiovascular complications were observed. Our results indicate that topical lidocaine cream offers significant pain relief of long duration without associated systemic side effects. PMID- 2921261 TI - The problem of Social Security disability determination for the burn patient. A report from the Committee on Rehabilitation of the American Burn Association (ABA). AB - The ABA Rehabilitation Committee has developed a form to be included in the hospital record at discharge that should facilitate the Social Security disability determination process for the burn patient. This form should aid in the disability determination process by guiding the Social Security disability examiner to the pertinent evidence of limitation and chronicity in the often cumbersome medical record and by emphasizing the multiple body system nature of the severe burn injury. PMID- 2921262 TI - Automated hydrotherapy pool water treatment system. AB - An automated hydrotherapy water treatment system was described that controls chemical pumps that maintain the pool's water pH and chlorine levels at the designated set points, regardless of the bather load. This system consists of sensing electrodes, a controller, and positive displacement pumps. Because outbreaks of waterborne infections have never been reported in facilities in which the pool water has been continuously maintained at pH 7.2 to 7.8 with a free available chlorine level of at least 1.0 ppm, we recommend that this type of water treatment system be installed in all public pools. PMID- 2921263 TI - The microbiology and cleaning of thermoplastic splints in burn care. AB - The ability of thermoplastic splints to be a vehicle for the transfer of microorganisms from the burn wound was explored. Twenty splints were evaluated and 10 (50%) were found to have recoverable microorganisms immediately after being removed from the burn patient. Air drying for 10 minutes was not shown to be an effective method of removing contaminating microorganisms. A cleaning protocol using a quaternary ammonia solution proved to be 100% effective in removing microorganisms from thermoplastic splint material. PMID- 2921264 TI - Have you tried the sandwich splint? A method of preventing hand deformities in children. AB - The prevention of contractures of the burned hand is an arduous problem in the young pediatric burn patient. Difficulty in applying splints, along with the time consuming fabrication of complex splints, led to the development of the "sandwich" splint. This easily produced splint provides a means of preventing and treating hand deformities in this patient age group. Positive results have been noted with the use of this splint in conjunction with the patient's usual active physical therapy program. PMID- 2921265 TI - Burn prevention begins at home ... your home. PMID- 2921266 TI - Promoting a burn center ... and burn prevention. PMID- 2921267 TI - Registered nurses and burn care facilities. Factors associated with turnover rates. AB - The health care system in the United States is suffering from a severe shortage of registered nurses. Burn treatment facilities are no exception to this phenomenon. As a result of this shortage, institutions have begun hiring less trained personnel such as licensed practical/vocational nurses (LPNs/LVNs), nursing assistants, burn technicians, and nursing students to fill the void. This shortage is so significant that the American Medical Association (AMA) has proposed a new category of bedside care provider, a "Registered Care Technologist" (RCT). The purpose of this paper is to determine the magnitude of the registered nurse shortage in burn care facilities. A second purpose is to identify factors associated with high turnover rates and to document the reasons why registered burn nurses are leaving their positions. PMID- 2921268 TI - The use of the bone curet in debridement of the burn wound and graft recipient sites. AB - We describe the use of the simple bone curet for the purpose of scraping and debriding partial-thickness burn wounds and other chronic wounds encountered by the burn surgeon before autograft placement. In our experience the instrument allows more efficient and safer operating room debridement than does the standard scalpel blade. PMID- 2921269 TI - In vivo and in vitro test for growth potential of liver cells from rats during early stage of hepatocarcinogenesis by 3'-methyl-4-dimethylaminoazobenzene. AB - A rapid increase in the fraction of small liver cells was observed in the liver of rats during the early stage of hepatocarcinogenesis by 3'-methyl-4 dimethylaminoazobenzene (3'-Me-DAB). The change in cell population was represented by the decrease in glucose-6-phosphatase activity and by the increase in number of gamma-glutamyltranspeptidase-positive cells. When DNA synthesis of liver cells from rats fed 3'-Me-DAB was measured by autoradiography in primary culture, it began to increase 2 weeks after the start of the carcinogen feeding, reaching a plateau level after 3 weeks. Liver cells from rats fed 3'-Me-DAB for 2 weeks or over demonstrated a remarkable resistance to the cytotoxic effect of the carcinogen (0.24 mM) in primary culture. Furthermore, liver cells from rats fed 3'-Me-DAB for 3 weeks or over proliferated in the presence of the carcinogen in primary culture. When liver cells from 3'-Me-DAB-fed and control rats were transplanted into syngeneic rat spleens, the former cells proliferated more vigorously than did the latter. The growth potential of liver cells from 3'-Me DAB-fed rats tended to be enhanced with time in the carcinogen feeding. Hepatocellular carcinomas developed in the host spleens implanted with liver cells from a rat fed 3'-Me-DAB for 8 weeks. As described above, liver cells from rats fed 3'-Me-DAB demonstrated much greater proliferative ability than normal control cells in vivo and in vitro. PMID- 2921270 TI - Chronic liver injury by thioacetamide and promotion of hepatic carcinogenesis. AB - To verify whether a mild, but prolonged liver injury by chemicals needing bioactivation causes both hepatic cirrhosis and the appearance of hepatocyte nodules and tumors (providing the liver has been exposed previously to initiating stimuli), diethylnitrosamine-initiated and uninitiated rats were administered thioacetamide at low dose (250 mg/l drinking water) for 6 months. Hepatocyte nodule incidence as well as changes in the drug-metabolizing system were followed at monthly intervals. In the uninitiated rats a micronodular liver cirrhosis slowly developed upon thioacetamide chronic administration; a few hepatocyte focal lesions of small size were seen from the 3rd month onward. By contrast in the diethylnitrosamine-initiated thioacetamide-treated rats the liver was macronodular because of the appearance and growth of many hepatocyte nodules; some hepatomas were also seen. During thioacetamide administration both uninitiated and diethylnitrosamine-initiated rats underwent a progressive decrease of the cytochrome P-450 liver content as well as of the activity of aminopyrine N-demethylase, ethoxycoumarin O-deethylase and ethoxyresorufin O deethylase. On the other hand, most components of the phase II of the drug metabolizing system were markedly enhanced. In conclusion, chronic administration of thioacetamide at low doses provided strong promoting stimuli for previously initiated hepatocytes. PMID- 2921271 TI - Effect of continuous vs intermittent application of 3-OH-tamoxifen or tamoxifen on the proliferation of the human breast cancer cell line MCF-7 M1. AB - The antiproliferative potency of 5 x 10(-7) M tamoxifen (TAM) and 3 hydroxytamoxifen (3-OH-TAM) was investigated during continuous (8 days) or intermittent (2 h every 2nd or 3rd day, respectively) application to the oestrogen-receptor-positive, estradiol-sensitive human mammary carcinoma cell line MCF-7 M1, a variant of MCF-7 wild type. Growth modulation was evaluated in parallel by counting cells and by measuring DNA content. Continuous incubation resulted in a growth inhibition to 21.8 +/- 3.2% by 3-OH-TAM and to 39.5 +/- 4.8% by TAM when compared with control cultures defined as 100%. Intermittent addition induced a growth reduction to 23.0 +/- 2.1% by 3-OH-TAM and to 41.2 +/- 2.4% by TAM in relation to 100% controls. Addition of 3-OH-TAM for 2 h only at day 1 resulted in an inhibition to 70.3 +/- 3.2%, again in relation to 100% controls. When TAM was administered once for 2 h at day 1 it induced an inhibition to 79.0 +/- 4.9% at day 8. The in vitro results indicate that (a) at 5 x 10(-7) M 3-OH TAM has a better antiproliferative effectiveness than TAM, (b) the intermittent application is as effective as continuous application (no significant difference), and (c) the addition once a week reveals only a slight growth reduction after 8 days of culture. Application of the long-living TAM results in continuously high serum concentrations, which have been shown to create resistant cell clones. Compared to TAM the 3-OH metabolite has a considerably shorter half life and its application in vivo reveals rise and fall of its serum concentrations. Since the presented data demonstrate that 3-OH-TAM is more potent than TAM and that the intermittent application is as effective as the continuous form, interval therapy with 3-OH-TAM may slow down the process of acquiring resistance to antioestrogens. PMID- 2921272 TI - Tumor cell recruitment in the mouse adenocarcinoma EO 771 directly demonstrated by double labeling with [3H]- and [14C] thymidine and flow cytometry. AB - Tumor cell recruitment in the mouse adenocarcinoma EO 771 after application of 1 beta-D-arabinofuranosylcytosine (AraCyt) has been directly demonstrated by double labeling with [3H]- and [14C]-thymidine. This method enables a quantitative study of the extent and time course of tumor cell recruitment in this solid mouse tumor. The results show that tumor cell recruitment is a continuous process that starts early after AraCyt application (about 4-8 h) and lasts about 1 day with a maximum at about 12 h after Ara-Cyt application. Up to 40% of all cells are recruited at that time. The recruited tumor cells re-enter the resting state after having passed through one cycle. PMID- 2921273 TI - Sensitivity of Burkitt lymphoma Daudi cells to inactive influenza virus. AB - Interaction of UV-inactivated influenza A/X47 virus at high multiplicity caused a rapid inhibition in cellular protein and DNA synthesis, thus arresting Burkitt lymphoma-derived Daudi cell multiplication, and eventually killing the cells. The mechanism of the cytolytic effect is presumably, linked to the increase in cell membrane permeability indicated by elevation in 51Cr release. This might be the consequence of the mass adsorption and/or penetration of viral particles. PMID- 2921274 TI - Tumor-initiating activity in mouse skin and carcinogenicity in rat mammary gland of dibenzo[a]pyrenes: the very potent environmental carcinogen dibenzo[a, l]pyrene. AB - Comparative studies of tumor-initiating activity in mouse skin and carcinogenicity in rat mammary gland were conducted with several dibenzo[a] pyrenes (DBPs). SENCAR mice were initiated with DB[a, e]P, DB[a, h]P, DB[a, i]P, DB[a, l]P and anthanthrene, and promoted with tetradecanoyl-phorbol acetate. The same compounds were tested by intramammillary injection in female Sprague-Dawley rats. Anthanthrene was inactive in both mouse skin and rat mammary gland. DB[a, e]P was a very weak tumor-initiator in mouse skin and was inactive in rat mammary gland. DB[a, h]P induced twice as many papillomas in mouse skin as DB[a, i]P, although both compounds exhibited similar tumor latencies and percentages of tumor-bearing mice. These two compounds induced similar numbers of mammary tumors, but treatment of the rats with DB[a, i]P resulted in a significantly larger number of adenocarcinomas. DB[a, l]P was toxic to both the mice and rats. Treatment of mouse skin with this compound led to an erythema, which delayed the beginning of promotion until the 3rd week after initiation. Despite this delay, papillomas began appearing 5 weeks after initiation with DB[a, l]P and the number of tumors increased rapidly. The compound was so toxic in the rats that half of the animals died in the first 9 weeks and the remaining animals were sacrificed after 15 weeks. Nonetheless, DB[a, l]P was the strongest carcinogen tested, inducing seven tumors per rat within 10 weeks. These results demonstrate that DB[a, l]P, which is present in tobacco smoke, is an extremely potent carcinogenic aromatic hydrocarbon. Furthermore, some of these compounds can serve as useful models for elucidating their mechanisms of activation. PMID- 2921275 TI - Iron-induced lipid peroxidation and inhibition of proliferation in Ehrlich ascites tumor cells. AB - The purpose of this study was to find further experimental evidence for the postulated negative association between the extent of lipid peroxidation in tumor cells and their proliferative behavior. After incubation of Ehrlich ascites tumor cells at 37 degrees C for 30 min with increasing concentrations of Fe(II) histidinate (Fe/His) the following parameters were determined: the formation of lipid hydroperoxides was measured fluorimetrically after reaction with dichlorofluorescein; 4-hydroxynonenal was determined by reversed-phase high pressure chromatography after derivatization with dinitrophenylhydrazine; as a third parameter of lipid peroxidation the formation of 2-thiobarbituric-acid reactive substances was determined. The proliferative activity was determined by measuring the growth rate in vivo after reimplantation i.p. of the tumor cells into mice. Trypan-blue exclusion tests for viability were performed before reimplantation. The reliability of the trypan-blue exclusion tests was checked by comparing the results with another parameter of viability, the release of the cytosolic enzyme lactate dehydrogenase. The concentration both of lipid hydroperoxides and of 2-thiobarbituric-acid-reactive substances showed a biphasic dependence on the concentration of Fe/His with maximal increase at iron concentrations of 0.25 mM and 0.1 mM respectively. 4-Hydroxynonenal, in contrast, showed a continuous increase up to 41.1 nM (corresponding to 0.58 pmol/10(9) cells) with increasing iron concentration in the range from 0.1 mM to 0.6 mM. The total number of tumor cells, when determined 5 days after reimplantation, continuously decreased with increasing iron concentration, showing half-maximal inhibition at about 0.22 mM Fe. The exclusion of the trypan-blue dye was unaffected by the presence of iron at any concentration used. Similarly, iron had no influence on the release of lactate dehydrogenase. The results support the hypothesis that 4-hydroxynonenal may act as an inhibiting messenger between endogenic lipid peroxidation and proliferation. PMID- 2921276 TI - Proteinase-like peptidase activities and oestrogen receptor levels in breast cancer tissue. AB - The relationship between proteinase-like peptidase activities and oestrogen receptor levels and status in breast cancer tissue homogenates from 61 patients with breast cancer has been evaluated. With Spearman's rank-order correlation analysis, significant positive correlations were observed between receptor levels and the activities of cathepsin-(B + L)-like, cathepsin-H-like, trypsin-like, plasminogen-activator-like and elastase-like peptidases. In addition, the activities of all but the latter enzyme were significantly higher in patients with receptor-rich tumours than in receptor-poor tumours, and this may have implications for future treatment regimens for patients with oestrogen-receptor rich tumours. The findings reported are consistent with the suggestion that in breast cancer there may be an association between steroid receptors and proteolytic enzymes such that the release of these enzymes may be under hormonal control. PMID- 2921277 TI - Isolation and characterization of low- and high-metastatic clones from murine RCT (Radiological, Chiba, and Toyama) sarcoma. AB - We have established low- and high-metastatic clones, named RCT(-) and RCT(+) cells, respectively, from the RCT (Radiological, Chiba, and Toyama) sarcoma spontaneously developed in a C3H/He male mouse by the limiting-dilution method in vitro or by the combination of the lung passages and limiting-dilution methods. After 20 serial passages in vitro, the metastatic potential of each clone did not alter. Morphologically, both cells were spindle-shaped, but RCT(+) cells were slightly thicker and larger than RCT(-) cells. The organization of actin containing filaments was slightly poorer in RCT(+) cells than that in RCT(-) cells. Marked differences were observed in their growth characteristics and adhesiveness to plastic or collagen-coated surfaces, that is, RCT(+) cells grew more slowly but could adhere more rapidly and firmly to the surfaces than RCT(-) cells. RCT(+) cells were agglutinated by all lectins used but several lectins could not agglutinate RCT(-) cells. These results could be a reflection of the difference in oligosaccharide residues on the surface of each cell and, in part, might reflect the difference in organization of the actin-containing filaments that regulate the mobility of lectin receptors. No significant difference between these cell clones was noted in their sensitivity to natural-killer-cell-mediated cytotoxicity in vitro. RCT(-) and RCT(+) cells are considered to be the most useful experimental model for the study of the certain sarcomas. PMID- 2921278 TI - Localization of nicotinic acetylcholine receptor alpha-subunit transcripts during myogenesis and motor endplate development in the chick. AB - In 15-d-old chick latissimi dorsi muscles, the nicotinic acetylcholine receptor (AChR) alpha-subunit mRNA is densely accumulated at the level of subsynaptic nuclei of the motor endplate (Fontaine et al., 1988). In this paper, using in situ hybridization with genomic probes, we further show that the expression of the AChR alpha-subunit gene in the embryo, revealed by the accumulation of mature mRNAs, starts in myotomal cells and persists during the first stages of muscle development in a majority of muscle nuclei. Subsequently, the distribution of AChR alpha-subunit mRNAs becomes restricted to the newly formed motor endplates as neuromuscular junctions develop. To assess the transcriptional activity of individual nuclei in developing muscles, a strictly intronic fragment of the AChR alpha-subunit gene was used to probe in situ the level of unspliced transcripts. AChR alpha-subunit unspliced transcripts accumulate around a large number of sarcoplasmic nuclei at embryonic day 11, but can no longer be detected at their level after embryonic day 16 in the embryo. A similar decrease in the accumulation of AChR alpha-subunit transcripts is observed between day 4 and day 6 in primary cultures of muscle cells. On the other hand, in vivo denervation and in vitro blocking of muscle electrical activity by the sodium channel blocker tetrodotoxin results in an increase in the labeling of muscle nuclei. Yet, only 6% of the muscle nuclei appear labeled by the strictly intronic probes after denervation. The possible significance of such heterogeneity of muscle nuclei during motor endplate formation in AChR gene expression is discussed. PMID- 2921279 TI - The actions of retinoids on cellular growth correlate with their actions on gap junctional communication. AB - Retinoic acid (a possible morphogen), its biological precursor retinol, and certain synthetic derivatives of retinol profoundly change junctional intercellular communication and growth (saturation density) in 10T 1/2 and 3T3 cells and in their transformed counterparts. The changes correlate: growth decreases as the steady-state junctional permeability rises, and growth increases as that permeability falls. Retinoic acid and retinol exert quite different steady-state actions on communication at noncytotoxic concentrations in the normal cells: retinoic acid inhibits communication at 10(-10)-10(-9) M and enhances at 10(-9)-10(-7) M, whereas retinol only enhances (10(-8)-10(-6) M). In v-mos-transformed cells the enhancement is altogether lacking. But regardless of the retinoid or cell type, all growth responses show essentially the same dependence on junctional permeability. This is the expected behavior if the cell to-cell channels of gap junctions disseminate growth-regulating signals through cell populations. PMID- 2921280 TI - Modulation of adipocyte differentiation by tumor necrosis factor and transforming growth factor beta. AB - Cultured TA1 adipocytes treated with tumor necrosis factor alpha (TNF) lose intracytoplasmic lipid and, over a period of days, come to resemble their predifferentiated progenitors (preadipocytes). To examine the extent to which this phenotypic reversion represents a return to a less differentiated cell, we examined three major characteristics that distinguish preadipocytes from adipocytes: (a) pattern of gene expression; (b) hormonal requirement for accelerated adipogenesis; and (c) pattern of protein synthesis. We found that within hours of TNF addition to adipocytes, mRNAs for genes whose expression is augmented during adipogenesis decreased to predifferentiated levels; in addition, like preadipocytes, TNF-treated adipocytes required exposure to hormones to accelerate adipogenesis. Further, the pattern of protein synthesis seen on polyacrylamide gels reverted to that seen before differentiation. Transforming growth factor-beta (TGF-beta) also caused a rapid decrease in expression of adipose genes when added to fully differentiated cells, an effect that was achieved by treatment with either TGF-beta 1 or TGF-beta 2. These effects were seen in the absence of a demonstrable proliferative response to either TNF or TGF beta. Thus characteristics that define the "terminally" differentiated state in adipocytes are subject to modulation by environmental influences. PMID- 2921281 TI - Perineurial cells coexpress genes encoding interstitial collagens and basement membrane zone components. AB - Perineurial cell cultures were established from the sciatic nerves of adult Wistar rats. Highly enriched cultures were studied with respect to the production of extracellular matrix components under conditions free from the influence of Schwann cells, axons, or the extracellular matrix of peripheral nerves. Indirect immunofluorescence staining revealed the presence of collagen type IV epitopes, and electron microscopy demonstrated patches of basement membrane on the perineurial cell surfaces. Collagenous fibrils with a diameter of 15-20 nm were also observed in the intracellular space. SDS-PAGE of radiolabeled medium proteins showed a pattern of bands suggesting the synthesis and secretion of fibronectin, and type I and IV collagens. Northern hybridizations revealed characteristic polymorphic mRNA transcripts corresponding to fibronectin, laminin B2 chain, as well as to the alpha-chain subunits of type I, III, and IV collagens. Furthermore, in situ hybridizations suggested expression of these genes by cultured perineurial cells without apparent heterogeneity within the cell populations. In situ hybridizations of sciatic nerve tissue from 2-wk-old rats also suggested that perineurial cells express alpha 1(I) and alpha 2(IV) collagen, as well as laminin B2 chain genes in vivo. This profile of matrix gene expression is different from that of Schwann cells, which do not synthesize fibronectin, or that of fibroblastic cells, which do not form a cell surface basement membrane. The capability of perineurial cells to express genes for the basement membrane zone and for interstitial collagens further adds to our understanding of the functional role of perineurial cells in developing and healing peripheral nerve, as well as in certain neoplastic lesions of neural origin, such as von Recklinghausen's neurofibromas. PMID- 2921282 TI - The level of Z-DNA in metabolically active, permeabilized mammalian cell nuclei is regulated by torsional strain. AB - Permeabilized nuclei from mammalian cells encapsulated within agarose microbeads in an isotonic buffer are active in transcription and replication (Jackson, D. A., and P. R. Cook. 1985. EMBO (Eur. Mol. Biol. Organ.) J. 4:913-918). Their DNA is intact and the nuclei are accessible to macromolecules. Myeloma nuclei prepared in this way were used to probe the extent of DNA negative supercoiling and the effects of altering torsional strain by binding radioactively labeled monoclonal antibodies to Z-DNA. Control experiments used monoclonal antibodies against a nonhistone chromosomal protein, HMG-17. On increasing the amount of anti-HMG-17 added, a binding plateau was reached encompassing a 200-fold range of antibody concentration. On binding anti-Z-DNA antibody, a similar broad plateau of constant binding was found encompassing a 100-fold range of antibody concentration. The latter result was taken as a measure of preexisting Z-DNA in the nuclei. Additional anti-Z-DNA antibody binding can be "induced" in the presence of much higher concentration of antibody, apparently by perturbing the B DNA/Z-DNA equilibrium. On inhibiting topoisomerase I with camptothecin, an elevated antibody binding plateau was found, suggesting that elastic torsional strain in the DNA is responsible for stabilizing the preexisting Z-DNA. This interpretation is supported by the fact that addition of small, nicking amounts of DNase I leads to a complete loss of antibody binding in the Z-DNA plateau region but not in the region of "induced" Z-DNA. PMID- 2921283 TI - Autonomous splicing and complementation of in vivo-assembled spliceosomes. AB - We have used an in vivo system generating assayable amounts of a specific pre mRNA to study the relationship between splicing and an operationally defined nuclear matrix preparation (NM). When NM is prepared by extraction of DNase I treated nuclei with an approximately physiological concentration of KCl (0.1 M), a portion of NM-associated precursor can be spliced in vitro in the presence of ATP and Mg2+ and in the absence of splicing extract ("autonomous splicing"). We propose that the autonomous reaction, which does not exhibit a temporal lag and is half-complete in 5 min, occurs in fully assembled, matrix-bound ribonucleoprotein complexes (in vivo spliceosomes). Extraction of the NM with concentrations of KCl greater than 0.4 M eliminates autonomous splicing but leaves behind preassembled complexes that can be complemented for splicing with HeLa cell nuclear extract. The splicing complementing factor, representing one or more activities present in the nuclear extract and also in the cytoplasmic S100 fraction, is relatively heat resistant, devoid of an RNA component, and does not bind to DEAE-Sepharose in 0.1 M KCl. It exists in the nucleus in two forms; bound to autonomous spliceosomes and free in the nucleoplasm. Biochemical features of the complementation reaction, and conditions for reversible uncoupling of the two splicing steps are described and discussed. PMID- 2921285 TI - Localization of phycoerythrin at the lumenal surface of the thylakoid membrane in Rhodomonas lens. AB - The thylakoids of cryptomonads are unique in that their lumens are filled with an electron-dense substance postulated to be phycobiliprotein. In this study, we used an antiserum against phycoerythrin (PE) 545 of Rhodomonas lens (gift of R. MacColl, New York State Department of Health, Albany, NY) and protein A-gold immunoelectron microscopy to localize this light-harvesting protein in cryptomonad cells. In sections of whole cells of R. lens labeled with anti-PE 545, the gold particles were not uniformly distributed over the dense thylakoid lumens as expected, but instead were preferentially localized either over or adjacent to the thylakoid membranes. A similar pattern of labeling was observed in cell sections labeled with two different antisera against PE 566 from Cryptomonas ovata. To determine whether PE is localized on the outer or inner side of the membrane, chloroplast fragments were isolated from cells fixed in dilute glutaraldehyde and labeled in vitro with anti-PE 545 followed by protein A small gold. These thylakoid preparations were then fixed in glutaraldehyde followed by osmium tetroxide, embedded in Spurr, and sections were labeled with anti-PE 545 followed by protein A-large gold. Small gold particles were found only at the broken edges of the thylakoids, associated with the dense material on the lumenal surface of the membrane, whereas large gold particles were distributed along the entire length of the thylakoid membrane. We conclude that PE is located inside the thylakoids of R. lens in close association with the lumenal surface of the thylakoid membrane. PMID- 2921284 TI - Changes in lysosome shape and distribution correlated with changes in cytoplasmic pH. AB - Lysosomes labeled by uptake of extracellular horseradish peroxidase display remarkable changes in shape and cellular distribution when cytoplasmic pH is experimentally altered. Normally, lysosomes in macrophages and fibroblasts cluster around the cell center. However, when the cytoplasmic pH is lowered to approximately pH 6.5 by applying acetate or by various other means, lysosomes promptly move outward and accumulate in tight clusters at the very edge of the cell, particularly in regions that are actively ruffling before acidification but become quiescent. This movement follows the distribution of microtubules in these cells, and does not occur if microtubules are depolymerized with nocodazole before acidification. Subsequent removal of acetate or the other stimuli to acidification results in prompt resumption of ruffling activity and return of lysosomes into a tight cluster at the cell center. This is correlated with a rebound alkalinization of the cytoplasm. Correspondingly, direct application of weak bases also causes hyperruffling and unusually complete withdrawal of lysosomes to the cell center. Thus, lysosomes appear to be acted upon by microtubule-based motors of both the anterograde (kinesin) type as well as the retrograde (dynein) type, or else they possess bidirectional motors that are reversed by changes in cytoplasmic pH. During the outward movements induced by acidification, lysosomes also appear to be smaller and more predominantly vesicular than normal, while during inward movements they appear to be more confluent and elongated than normal, often becoming even more tubular than in phorbol-treated macrophages (Phaire-Washington, L., S. C. Silverstein, and E. Wang. 1980. J. Cell Biol. 86:641-655). These size and shape changes suggest that cytoplasmic pH also affects the fusion/fission properties of lysosomes. Combined with pH effects on their movement, the net result during recovery from acidification is a stretching of lysosomes into tubular forms along microtubules. PMID- 2921286 TI - Asymmetric behavior of severed microtubule ends after ultraviolet-microbeam irradiation of individual microtubules in vitro. AB - The molecular basis of microtubule dynamic instability is controversial, but is thought to be related to a "GTP cap." A key prediction of the GTP cap model is that the proposed labile GDP-tubulin core will rapidly dissociate if the GTP tubulin cap is lost. We have tested this prediction by using a UV microbeam to cut the ends from elongating microtubules. Phosphocellulose-purified tubulin was assembled onto the plus and minus ends of sea urchin flagellar axoneme fragments at 21-22 degrees C. The assembly dynamics of individual microtubules were recorded in real time using video microscopy. When the tip of an elongating plus end microtubule was cut off, the severed plus end microtubule always rapidly shortened back to the axoneme at the normal plus end rate. However, when the distal tip of an elongating minus end microtubule was cut off, no rapid shortening occurred. Instead, the severed minus end resumed elongation at the normal minus end rate. Our results show that some form of "stabilizing cap," possibly a GTP cap, governs the transition (catastrophe) from elongation to rapid shortening at the plus end. At the minus end, a simple GTP cap is not sufficient to explain the observed behavior unless UV induces immediate recapping of minus, but not plus, ends. Another possibility is that a second step, perhaps a structural transformation, is required in addition to GTP cap loss for rapid shortening to occur. This transformation would be favored at plus, but not minus ends, to account for the asymmetric behavior of the ends. PMID- 2921288 TI - The metabolic effects of mild hypothermia on global cerebral ischemia and recirculation in the cat: comparison to normothermia and hyperthermia. AB - The metabolic effects of graded whole body hypothermia on complete global cerebral ischemia and recirculation was investigated in the cat. Hypothermia was induced to one of three levels prior to ischemia; T = 26.8 degrees +/- 0.5 degrees C (n = 4), T = 32.1 degrees +/- 0.2 degrees C (n = 5), and T = 34.6 degrees +/- 0.3 degrees C (n = 6), and maintained constant throughout 16 min of ischemia and 1.5-2 h of recirculation. Intracellular cerebral pH and relative concentrations of high-energy phosphate metabolites were continuously monitored, using in vivo 31P nuclear magnetic resonance (NMR) spectroscopy. Except for the first 4 min of ischemia, no significant differences were detected in the response of adenylate intensities and intracellular pH to ischemia and recirculation between the hypothermic groups. The three hypothermic groups were then pooled into one group, and the data compared to previously published data from a normothermic group, T = 38.4 degrees +/- 0.6 degrees C (n = 14), and a hyperthermic group, T = 40.6 degrees +/- 0.2 degrees C (n = 9), subjected to the identical ischemic and NMR measurement protocols. The hypothermic animals exhibited a statistically significant reduction of cerebral intracellular acidosis, both during ischemia and recirculation, as well as a more rapid return of adenylate intensities during recirculation, compared to the normothermic or hyperthermic groups. The data thus suggest that mild hypothermia has an ameliorative affect on brain energy metabolism and intracellular pH under conditions of complete global cerebral ischemia and recirculation. PMID- 2921287 TI - Differential axonal transport of isotubulins in the motor axons of the rat sciatic nerve. AB - The axonal transport of the diverse isotubulins in the motor axons of the rat sciatic nerve was studied by two-dimensional polyacrylamide gel electrophoresis after intraspinal injection of [35S]methionine. 3 wk after injection, the nerve segments carrying the labeled axonal proteins of the slow components a (SCa) and b (SCb) of axonal transport were homogenized in a cytoskeleton-stabilizing buffer and two distinct fractions, cytoskeletal (pellet, insoluble) and soluble (supernatant), were obtained by centrifugation. About two-thirds of the transported-labeled tubulin moved with SCa, the remainder with SCb. In both waves, tubulin was found to be associated mainly with the cytoskeletal fraction. The same isoforms of tubulin were transported with SCa and SCb; however, the level of a neuron-specific beta-tubulin subcomponent, termed beta', composed of two related isotubulins beta'1 and beta'2, was significantly greater in SCb than in SCa, relative to the other tubulin isoforms. In addition, certain specific isotubulins were unequally distributed between the cytoskeletal and the soluble fractions. In SCa as well as in SCb, alpha''-isotubulins were completely soluble in the motor axons. By contrast, alpha''' and beta'2-isotubulins, both posttranslationally modified isoforms, were always recovered in the cytoskeletal fraction and thus may represent isotubulins restricted to microtubule polymers. The different distribution of isotubulins suggests that a recruitment of tubulin isoforms, including specific posttranslational modifications of defined isoforms (such as, at least, phosphorylation of beta' and acetylation of alpha'), might be involved in the assembly of distinct subsets of axonal microtubules displaying differential properties of stability, velocity and perhaps of function. PMID- 2921289 TI - Cytosolic free calcium, NAD/NADH redox state and hemodynamic changes in the cat cortex during severe hypoglycemia. AB - Using indo-1, a fluorescent Ca2+ indicator, in vivo fluorometric measurements were made of changes in cytosolic free Ca2+, NAD/NADH redox state, and hemodynamics directly from the cat cortex during and after severe insulin-induced hypoglycemia. Cytosolic free Ca2+ started to increase when the EEG became isoelectric, remained at a significantly high level (p less than 0.05) during the period of isoelectric EEG (IEEG), and recovered to the control level 6 min following an intravenous infusion of glucose. The NAD/NADH redox state oxidized significantly during IEEG and then recovered rapidly to the control level after the glucose infusion. Local cortical blood volume (LCBV) increased gradually during the progression of hypoglycemia, reaching the maximal level (146 +/- 7%) at the end of IEEG, and then started to recover. The mean transit time (MTT) through the cortical microcirculation was shortened during the IEEG (control: 3.84 +/- 0.41 s versus IEEG: 2.73 +/- 0.17 s, p less than 0.05), whereas it was prolonged during the 30-min recovery period (5.68 +/- 0.58 s, p less than 0.05). Local cortical blood flow calculated from the LCBV and MTT showed a twofold increase 5 min into IEEG (201 +/- 27% of control, p less than 0.05), recovered 15 min into the recovery period, and then decreased to 77% of control (p less than 0.05) by 30 min. The data support the hypothesis that hypoglycemic brain damage might be mediated by an elevation of cytosolic free calcium. PMID- 2921290 TI - Cerebral energy metabolism in cyanide encephalopathy. AB - This study documents the effects of an intracarotid artery injection of a lethal threshold amount of KCN (2.5 mg.kg-1) on the energy metabolism and histology of the rat brain. This dose of KCN resulted in a rapid abolition of electroencephalographic activity, which remained essentially absent for up to 3 h. Cerebral metabolite measurements 0.25 h after KCN infusion indicated a 52% reduction in cytochrome oxidase activity, a 600% increase in lactate, a 32% reduction in ATP, a 73% increase in ADP, and an 85% decrease in glycogen. Measurements of the above energy metabolites over the ensuing 7 days showed a return to control of all metabolites by 6-24 h. Corresponding to the normalization of energy metabolism was a return of EEG and conscious activity. Histological examination of cyanide-exposed animals revealed a paucity of change with only one animal at 0.5 h showing several dark neurons, two animals at 1 h with minor pallor of corpus callosum and caudate-putamen, and one animal at 48 h with a small hippocampal infarction. It is concluded that it may be impossible to produce a serious enough disruption of cerebral metabolism with KCN injection, to produce neuronal damage by purely "histotoxic" mechanisms. PMID- 2921291 TI - Cerebral vascular volume after repeated ischemic insults in the gerbil: comparison with changes in CBF and brain edema. AB - The time course of changes in cerebral intravascular volume was evaluated during 24 h following a series of three 5-min carotid artery occlusions spaced at 1-h intervals and compared with the changes occurring after single 5- or 15-min occlusions. Quantitative estimates of cerebral red cell volume, plasma volume, and total blood volume were obtained from the distribution spaces of 51Cr-labeled erythrocytes and 125I-albumin infused prior to killing at varied recirculation intervals. Significant reductions in vascular volume occurred in all ischemic brain regions within 1 h following a single 5-min occlusion, which recovered to control values within 6 h. A similar time course was seen after repeated occlusions. The reductions in volume remained significant at 6 h after a single 15-min occlusion, but there was no difference from control by 24 h. Thus, the time course of total vascular volume correlates well with that of CBF changes previously described, and both blood flow and blood volume are at normal levels during the time of severe edema 24 h after repeated occlusions. Calculated cerebral hematocrit was 60-70% of that obtained from the femoral artery, but was identical in all brain regions and was constant throughout the postischemic recirculation period, with the exception of a transient reduction in both peripheral and cerebral hematocrit observed at 6-h recirculation following single 15-min occlusions. These results suggest that changes in CBF and blood volume reflect primarily the status of larger vessels and that values in the normal range may be observed even under conditions of severe edema and impaired perfusion at the capillary level. PMID- 2921292 TI - Cerebral superoxide anion generation during seizures in newborn pigs. AB - Cerebral superoxide anion generation during bicuculline-induced seizures was measured in newborn pigs. Using two closed cranial windows inserted over the parietal cortices, superoxide dismutase (SOD)-inhibitable nitroblue tetrazolium (NBT) reduction was determined during 20 min of seizure activity induced by bicuculline, 5 mg/kg i.v. A modest increase in SOD-inhibitable NBT reduction was observed in piglets subjected to bicuculline-induced seizure activity (2.4 +/- 0.6 pmol/mm2 in 20 min) when compared to control piglets (0.4 +/- 0.3 pmol/mm2 in 20 min). Pretreatment with indomethacin (5 mg/kg i.v.) reduced SOD-inhibitable NBT reduction during seizures to the control level (0.5 +/- 0.4 pmol/mm2 in 20 min). We conclude that small quantities of superoxide anion radical are produced by newborn pig brain during bicuculline-induced seizures and that cyclooxygenase metabolism of arachidonic acid appears to be a major source. PMID- 2921293 TI - CNS stimulation and PGE2 release. III. Pentamethylenetetrazole-induced seizures. AB - Measurement of prostaglandin E2 (PGE2) in the ventriculocisternal perfusate of the halothane anesthetized, artificially ventilated cat has revealed low but measurable levels of the prostanoid (64 +/- 5 pg/min). Administration of pentamethylenetetrazole (PTZ) resulted in a rapid appearance of paroxysmal bursting, the magnitude and duration of which was dose dependent. During the 30 min interval after seizure initiation, PGE2 secretion rates into the ventriculocisternal perfusate rose by five- to sevenfold. Though the initial rate of PGE2 secretion correlated closely with the initial magnitude of bursting, there were significant differences, viz. the time courses. Thus, after a low dose of PTZ (200 mg/kg) the increase and return to normal of PGE2 secretion was time locked with the onset and offset of seizures. In contrast, after high doses of PTZ (250 mg/kg i.v.), seizure activity returned to near baseline by 90 min, while the levels of PGE2 secretion remained elevated for periods in excess of 150 min. Pretreatment with clonazepam (CLP: 3 mg/kg i.v. infusion) blocked seizures otherwise induced by PTZ (250 mg/kg) and the increase in PGE2 secretion. CLP administration 60 min after the initiation of seizures, blocked further seizure activity but did not alter the elevated secretion of PGE2. We thus believe these data jointly support the hypothesis that under intense paroxysmal bursting there is a change in neuronal state such that large stores of free fatty acids are available either because they have accumulated during the seizure because of a continued Ca2+ influx or the presence of large and continuing concentrations of Ca2+ accumulating in the cytosol secondary to energy failure. PMID- 2921294 TI - Mechanisms of cerebrovascular O2 sensitivity from hyperoxia to moderate hypoxia in the rat. AB - Cerebrovascular dilation over PaO2 ranging from hyperoxia to moderate hypoxia is unexplained. We hypothesize that tissue acidosis is the cause. Local cortical cerebral blood flow (LCBF), tissue hydrogen ion concentration [H+]t, and tissue PO2 (PtO2) were measured with microelectrodes in the parietal cortex of 18 rats during a 30-min steady state on 60 to 10% inspired O2 (PaO2, 300 to 40 torr) during 40% N2O analgesia. Five rats kept on 60% O2/40% N2O served as controls. In 18 rats at a PaO2 of 275 +/- 7 torr (mean +/- SEM) and PaCO2 of 35 +/- 1 torr, cerebral values were: LCBF = 129 +/- 23 (mean +/- SEM) ml.100 g-1.min-1; [H+]t = 62 +/- 6 nM; and PtO2 = 25 +/- 3 torr. As PaO2 was reduced from about 300 to 40 torr, changes in these variables in percentage of control with respect to PaO2, were described by the following equations, all at P less than 0.0001: LCBF = 85.9 + 5,572/Pao2; [H+]t = 97.15 + 1,012/PaO2; and PtO2 = 108.8 - 3,492/PaO2. Simultaneous solution of the LCBF and [H+]t equations at various PaO2 revealed a slope of 8.82%/nM. Direct correlation between LCBF in ml.100 g-1.min-1 and [H+]t in nM revealed a linear relationship defined by the equation Y = -7.472 + 1.6705X (r = 0.6426) for [H+]t between 56 and 160 nM (pH = 7.25 and 6.80) but no correlation at [H+]t values between 56 and 32 nM (pH = 7.25 to 7.50). Cerebrovascular tone is directly correlated with [H+]t during progressive, 30-min steady-state reduction in PaO2 from 350 to 40 torr. PMID- 2921295 TI - Acetylcholine and vasoactive intestinal peptide in cerebral blood vessels: effect of extirpation of the sphenopalatine ganglion. AB - The innervation of cerebral blood vessels by nerve fibers containing acetylcholinesterase (AChE) and vasoactive intestinal peptide (VIP) and the vasomotor effects of the two neurotransmitters have been analyzed in the rat following the uni- or bilateral removal of the sphenopalatine ganglion (SPG), which is thought to be the major origin of this innervation. Histochemistry of AChE-positive nerve fibers and the immunoreactivity toward VIP revealed only a 30% reduction in the innervation pattern of the rostral part of the cerebral circulation following the operation. At approximately 4 weeks postoperatively, the original nerve network was restored. Quantitative measurements of cholineacetyltransferase activity and VIP revealed similar reductions in the levels of collected large cerebral arteries at the base of the brain and in small pial vessels overlying the cerebral cortex at the various postoperative times following uni- or bilateral removal of the SPG. The two techniques thus complemented each other. Vasomotor reactivity to acetylcholine (ACh) and VIP was examined in proximal segments of the middle cerebral artery at the various postoperative times. Generally, the removal of the SPG had no effect on the responses to ACh or VIP. The evidence indicates that only approximately one-third of the cholinergic/VIP innervation of the rostral part of the cerebral circulation originates in the SPG. PMID- 2921296 TI - Effect of hemoglobin on neurogenic responses and cholinergic parameters in porcine cerebral arteries. AB - Electrically stimulated neurogenic vasodilation and endothelial-dependent cholinergic vasodilation in cerebral arteries are both blocked by hemoglobin. To determine if neurogenic vasodilation has a cholinergic component, we examined the effect of hemoglobin on neurogenic responses and perivascular cholinergic parameters in isolated porcine cerebral arteries. The perfused circle of Willis has a mixed response to transmural nerve stimulation (TNS) that is predominantly vasodilation. Exposure to hemoglobin (5 microM) causes constriction of this preparation while simultaneously blocking TNS-induced vasodilation. At similar concentrations, however, hemoglobin did not alter electrically stimulated, tetrodotoxin-sensitive release of acetylcholine. Hemoglobin also had no effect on neuronal choline uptake or esteratic inactivation of acetylcholine. These results demonstrate the ability of low concentrations of hemoglobin to alter cerebral neurogenic vasodilation. The failure of hemoglobin to affect any aspect of cholinergic transmission, however, provides further evidence against a direct vasodilatory role for acetylcholine as a terminal transmitter in isolated cerebral blood vessels. PMID- 2921297 TI - The transport of leucine and aminocyclopentanecarboxylate across the intact, energy-depleted rat blood-brain barrier. AB - The transport across the blood-brain barrier of the large neutral amino acid leucine and the nonmetabolised aminocyclopentanecarboxylate (ACPC), of similar molecular size, was studied in the perfused, energy-depleted rat brain. It was found that when both leucine and ACPC were perfused for periods of up to 10 min their accumulation in the brain increased in a linear fashion. The ratio of perfusate radioactivity per milliliter and tissue radioactivity per gram (Rt/Rp) rose to above unity for both leucine and ACPC, indicating continued uptake against a concentration gradient of the radiolabel within the CNS. When the effect of increasing the concentration of the amino acid upon its influx into the brain was studied, it was found that under these conditions the kinetics of transport for both leucine and ACPC were of a similar order of magnitude to those reported previously in vivo. The values for the Michaelis constant for transport (Km), maximum rate of transport (Vmax), and the constant for the apparently linear, nonsaturable component (Kd) for leucine into the cerebrum were 84.5 +/- 29.0 microM, 45.5 +/- 1.5 nmole/min/g, and 2.62 +/- 0.15 microliters/min/g, respectively, and for ACPC 381 +/- 64 microM, 54.0 +/- 1.5 nmole/min/g and 0.35 +/- 0.10 microliter/min/g, respectively. Comparing this data with previously reported values it is suggested that the transport of leucine into the central nervous system from a perfusate or bolus where no other competing amino acids are present, is flow dependent. Furthermore, ACPC enters the brain almost entirely by a carrier-mediated process, with little or no nonsaturable influx despite a similar oil/water partition coefficient as leucine. PMID- 2921299 TI - Microbial contamination of cosmetics and personal care items in Egypt--eye shadows, mascaras and face creams. AB - We examined a total of 150 samples, including 27 eye shadows, 27 mascaras and 96 face creams, for their microbial contents. Mascaras were generally more contaminated than eye shadows. More than 75% of the examined eye shadows contained fewer than 100 c.f.u./g aerobic bacterial count compared to 63% of the mascaras examined. Viable bacteria were not recovered from 61% and 48% of the eye shadows and mascaras respectively. While 4% of the eye shadows were heavily contaminated (contained more than 10(4) c.f.u./g), 15% of the mascaras were as heavily contaminated (with more than 10(4) c.f.u./ml of bacteria). Face creams were generally more heavily contaminated than eye shadows and mascaras. More than 70% of the examined creams contained more than 100 c.f.u./g of bacteria compared to 23% and 37% of eye shadows and mascaras respectively. Only 5% of the face creams were heavily contaminated. However, 27% of the creams were contaminated with more than 10(3)-10(4) c.f.u./g of bacteria compared to none in this range for both eye shadows and mascaras. Qualitative tests for detection of hazardous bacteria showed that none of the eye shadows were contaminated with any of those micro-organisms. Out of nine items of a specific brand of mascara, three isolates of Pseudomonas aeruginosa, one isolate of Citrobacter freundii and one isolate of Klebsiella pneumonia were detected. Among the creams, two brands showed the highest contamination levels with more than 85% of the tested samples containing more than 10(3) c.f.u./g fungi and at least 10(4) c.f.u./g bacteria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2921298 TI - The effect of a low pH saline perfusate upon the integrity of the energy-depleted rat blood-brain barrier. AB - The effect of a low pH perfusate upon the integrity of the rat blood-brain barrier was studied using an in situ supravital brain perfusion technique in which high-energy phosphates are depleted. Control animals were perfused for 10 min with a Ringer's salt solution containing the metabolic inhibitor 2,4 dinitrophenol (DNP) and adjusted to a pH of 7.4. In two separate experimental groups the perfusate, consisting of either the same medium as the controls or with additional buffering from Tris maleate, was switched after 5 min at a pH of 7.4, to a medium adjusted to pH 5.5 with lactic acid. Following a total perfusion time of 10 min, the integrity of the blood-brain barrier was assessed using the small molecular weight tracer [14C]mannitol. The cerebral perfusate flow rates (CPFR) after 10 min of perfusion were also determined in the three groups by perfusing for 40 s with [14C]iodoantipyrine. In each group, mannitol was excluded from the tissue of the brain to the same degree as has been previously reported in vivo, indicating an intact blood-brain barrier. There was also no significant pH-dependent change in CPFR. Ultrastructural examination of animals that had been perfusion fixed following in situ perfusion revealed no obvious differences between the cerebral endothelium of the control and low pH perfused animals. These results demonstrate that in the absence of energy-producing metabolism a perfusate pH of 5.5 is insufficient to disrupt the blood-brain barrier. PMID- 2921300 TI - Microbial contamination of cosmetics and personal care items in Egypt--shaving creams and shampoos. AB - We examined a total of 192 samples, including eight different brands of shaving cream and eight brands of shampoo, for their total aerobic bacterial, coliforms and fungal counts. Shaving creams were more heavily contaminated with bacteria than shampoos. Viable bacterial were not recovered from 57% and 10% of shampoos and shaving creams, respectively. Only 3% of shaving creams were heavily contaminated with more than 10(4) c.f.u./g, while none of the shampoos contained such a high number of bacteria. With regard to the medium range contamination levels, 52% of shaving creams showed bacterial counts ranging from 10(2) to 10(3) c.f.u./g or ml, compared to 15% of shampoos which were contaminated to the same level. Fourteen per cent of shaving creams were contaminated with greater than 10(3)-10(4) c.f.u./g or ml, compared to 1% of the shampoos. No coliforms were recovered from either the shaving creams or the shampoos; however, Staphylococcus spp. were detected in six samples of both shampoos and shaving creams. Some of these Staphylococci, were aureus type. One isolate of Pseudomonas aeruginosa was also detected in a sample of shampoo. The incidence of fungal contamination was much less than the bacterial contamination. No viable fungi were recovered from 88% and 76% of the shaving creams and shampoos, respectively. The majority of the remaining samples, for both products, were contaminated with less than 100 fungal cell/g or ml. The pH of all the tested samples was alkaline (pH 7.2-9), which is well known to inhibit fungal contamination. PMID- 2921301 TI - High-performance liquid chromatographic analysis of theophylline in serum and its use in therapeutic drug monitoring. AB - A rapid, highly sensitive high-performance liquid chromatographic method has been developed for the determination of theophylline in serum using beta hydroxyethyltheophylline as an internal standard (IS). Theophylline and IS were extracted from serum using a mixture of dichloromethane: isopropanol (90: 10, v/v) and eluted from a 5 microns, C-18 reversed-phase column at 60 degrees C with a mobile phase consisting of sodium acetate buffer-acetonitrile (90:10, v/v), at a flow rate of 1 ml/min with ultraviolet detection at 280 nm. Each analysis required no longer than 7 min to perform. Quantification was achieved by the measurement of the peak: height ratio and the relative and absolute recoveries varied from 86 to 100%. Within-day coefficients of variation ranged from 2.9 to 5.1% and between-day coefficients of variation from 1.1 to 5.9% in subtherapeutic, therapeutic, and toxic concentrations. PMID- 2921302 TI - The stability of amoxycillin sodium in normal saline and glucose (5%) solutions in the liquid and frozen states. AB - The stability of a 1% w/v solution of amoxycillin sodium in normal saline and in glucose (5%) solutions was examined in the liquid and frozen states over the temperature range -26-60 degrees C. It was found that under all conditions amoxycillin sodium was much less stable in glucose (5%) solution. Freezing the solutions markedly reduced amoxycillin sodium stability. Maximum degradation rates in the frozen state occurred over the temperature range -7.5 degrees C to 6.5 degrees C in normal saline and at -8.9 degrees C in glucose (5%) solutions. For example, in normal saline the liquid state t90 (time for the concentration to decrease to 90% of its initial value) at 0 degree C of 252 h, was reduced to 8 h at -6.5 degrees C and increased to 14 h at -19.2 degrees C. In glucose (5%) solution comparative values of 12.5 h at 0 degree C, 2.5 h at -6.5 degrees C and 8.4 h at -19.2 degrees C were found. Amoxycillin sodium is very unstable in these solutions even at -26 degrees C. Maximum stability of the solutions examined in this study was at 0 degree C in normal saline and at -26 degrees C in glucose (5%) where the t90 value was 25.5 h. PMID- 2921303 TI - Patients' knowledge concerning their medications on discharge from hospital. AB - Fifty patients were interviewed, on discharge from hospital, about their medications. Nine (18%) patients did not know, and a further four (8%) had inappropriate beliefs about why they were taking at least one of their discharge medications. Very few patients knew of significant side-effects which they might expect, or precautions which they should take, and over half did not know how long they were to continue taking their medicines. A small proportion was unable to read the bottle or open the container. Thus, even patients who, by virtue of an in-patient stay, have had a prolonged opportunity for education regarding their medicines have very little knowledge of their medicines upon discharge from hospital. PMID- 2921304 TI - Optimization of blood sampling time after intravenous bolus doses of gentamicin. AB - Comparisons were made, based on a one-compartment model, between predicted serum concentrations obtained at various sampling times after i.v. bolus and i.m. injections of gentamicin. Post-dose concentrations 1 h after i.m. injection were within 3% of the maximum concentration at steady-state, indicating that this was the optimal sampling time. Serum concentrations 1 h post-i.v. bolus were less than 7% different from those 1 h post-i.m. injection. In a clinical trial, blood samples taken earlier during the distribution phase of the drug, after an i.v. bolus, resulted in serum concentrations which were up to 74% higher than concentrations at 1 h. A survey of a sample of U.K. hospitals showed that only 41% were taking samples at 1 h post i.v. bolus of gentamicin. The majority of hospitals recommended a range of post-dose serum concentrations between 4 and 12 mg/l for patients with septicaemia, but when adjusted for errors related to sampling time, 36% of hospitals recommended a minimum which was equivalent to less than 4 mg/l at 1 h post dose. Post-dose concentrations of gentamicin should be measured in samples taken 1 h after either i.v. bolus and i.m. injections. PMID- 2921305 TI - Population pharmacokinetics of phenytoin from routine clinical data in Japan. AB - Routine clinical pharmacokinetic data collected from out-patients who received phenytoin were analysed to estimate population pharmacokinetic parameters. There were 505 steady-state phenytoin concentrations and associated dosage rates (mg/day) from 220 out-patients. The data were analysed using NONMEM, a computer program designed for population pharmacokinetic analysis that allows pooling of data from many individuals. The influence of weight on the maximum elimination rate (Vm) and age on the Michaelis-Menten constant (Km) or the influence of dosage form on the bioavailability (F) of phenytoin were investigated. The Vm and Km of a 60-kg adult out-patient were estimated to be 369 mg/day and 3.67 mg/l, respectively. The parameter of a power function of weight was estimated to adjust Vm for body size. The best function adjusts Vm in proportion to weight to the 0.55 power. The Km for patients less than 15 years old was 16% less than that for adults. When the F of phenytoin is assumed to be 100% in the patients prescribed a tablet, the F value in the patients prescribed a powder was 89.5%. PMID- 2921306 TI - Antithyroid and goitrogenic effects of millet: role of C-glycosylflavones. AB - Pearl millet [Pennisetum millet (L.) leeke] is the main source of food energy for the rural poor in many areas of the semiarid tropics. Epidemiological evidence suggests that millet may play a role in the genesis of endemic goiter in these areas, and sparse experimental data in rats support this suspicion. This study was undertaken to determine in vivo in rats and in vitro using porcine thyroid slices and a thyroid peroxidase (TPO) assay the goitrogenic and antithyroid effects of millet diets, extracts of millet, and certain pure compounds contained therein. For use in these studies, whole grain millet was progressively dehulled to yield successively four bran and four flour fractions in which direct analyses revealed progressively lower concentrations of C-glycosylflavones. In vivo feeding of bran fraction 1, that richest in C-glycosylflavones, led to a significant increase in thyroid weight and antithyroid effects. Feeding of bran fraction 2, the next richest in C-glycosylflavones, produced similar, but less marked, changes. In vitro studies of 125I metabolism using porcine thyroid slices indicated that extracts of bran fractions 1 and 2 were most potent, producing changes similar to those produced by methimazole (MMI). At a concentration of 60 mumol/L, glucosylvitexin, the major C-glycosylflavone present in millet, had effects comparable to those of 1 mumol/L MMI. Similarly, in studies of porcine TPO, extracts of bran fraction 1 caused pronounced (85%) inhibition of enzyme activity, and progressively less inhibition was induced by extracts of bran fractions 2, 3, and 4. Overall, the TPO-inhibiting activities of the various millet fractions closely correlated with their C-glycosylflavone concentrations. Three C-glycosylflavones present concentrations. Three C-glycosylflavones present in millet, glucosylvitexin, glycosylorientin, and vitexin, also inhibited TPO activity. Thus, in vivo and in vitro studies revealed that millet diets rich in C glycosylflavones produce goitrogenic and antithyroid effects similar to those of certain other antithyroid agents and small doses of MMI. We conclude that in areas of iodine deficiency in which millet is a major component of the diet, its ingestion may contribute to the genesis of endemic goiter. PMID- 2921307 TI - Differences between circadian and ultradian organization of cortisol and melatonin rhythms during activity and rest. AB - We compared the cortisol and melatonin circadian and ultradian rhythms in normal men using two approaches: 1) the men were exposed successively to two conditions, one normal and a second chosen to alter differently each of the hormones, i.e. complete bedrest for 34 h (supine, fasting, and under dim light), and 2) analyses of the rhythms using a combination of curve smoothing for the description of the 24-h rhythm, and peak detection and spectral analysis for the measurement of periodic phenomena. Blood was sampled every 30 min from 0700-0700 h. A diurnal rhythm was detected for both hormones, with different underlying frequencies. Plasma cortisol had an ultradian rhythm of 8 h. From 0000-0800 h (night) and 0830 1600 h (early day), the pulsatile activity and baseline values of cortisol were high, while from 1630-2400 h (late day), these variables were low. During complete bedrest, pulsatile activity and baseline values were even higher during the night period, and the nocturnal peak of cortisol, usually present between 0300-1000 h, was split in two, with an early peak at 0000-0400 h. There were two specific events during the day associated with synchronous, high amplitude pulses: awakening and eating at noon. No such pulses occurred at suppertime or when the men fasted. Melatonin secretion was organized around a 5.5-h period. In the rest condition, plasma melatonin values were higher during the night. The 24 h rhythms of cortisol and melatonin were temporally related. Plasma melatonin began to rise when plasma cortisol was at its lowest, it peaked when cortisol began to rise, and it began to decrease when cortisol reached its peak, with a 5 h phase delay between plasma cortisol and melatonin rise at night. In summary, melatonin and cortisol rhythms have different ultradian frequencies, suggesting an intrinsic difference in the mechanisms controlling their secretion. In addition, their responses to restricted physical activity in an environment with dim light were completely different; for plasma melatonin, the change was primarily quantitative, with an increase in total production especially at night, while for plasma cortisol, there was more of a qualitative change, with different patterns of pulsatile activity and possible splitting of the nocturnal peak. The differences in the ultradian organization of these two hormones imply that the correlation between their peaks must depend on a third factor, which is likely to be the 24-h organization of the day. PMID- 2921308 TI - Thyroid peroxidase activity-inhibiting immunoglobulins in patients with autoimmune thyroid disease. AB - The thyroid microsomal antibody (M-Ab) has been found to be an antibody against thyroid peroxidase (TPO), and such antibodies have been reported not only to bind TPO but also to directly inhibit TPO activity. In this study we investigated the relationship between TPO activity-inhibiting immunoglobulin (TPII) and thyroid function in 55 untreated patients with hyperthyroidism due to Graves' disease and 35 untreated patients with Hashimoto's disease. TPO partially purified from the microsomal fraction of Graves' thyroid tissue by Sephacryl S-300 gel filtration was incubated with immunoglobulin (Ig) fractions of serum prepared by precipitation with 15% polyethylene glycol. At the end of incubation, TPO activity was measured by a guaiacol assay. The TPII level was expressed as the TPII index, defined as the inhibition of TPO activity by patient Ig divided by inhibition produced by a known positive Ig. We also measured serum free T4, free T3, and TSH concentrations and anti-M-Ab titers, the latter by a microenzyme linked immunosorbent assay. When a positive TPII index was defined as more than the mean + 2 SD of the TPII index (0.38) for 15 normal subjects, 13 patients with Graves' disease and 14 patients with Hashimoto's disease had positive TPII index values. There was a positive correlation between the TPII index values and the M Ab titers in patients with either Graves' disease (r = 0.38; P less than 0.01) or Hashimoto's disease (r = 0.52; P less than 0.01). The mean TPII index in patients with Hashimoto's disease was significantly higher than that in patients with Graves' disease [0.38 +/- 0.42 (+/- SD) vs. 0.19 +/- 0.41; P less than 0.05]. The slope of the regression line between the TPII index values and the M-Ab titers for patients with Hashimoto's disease was steeper than that for patients with Graves' disease. The mean serum free T4 concentration was significantly lower in those patients with Hashimoto's disease who had positive TPII index values than in those with negative TPII index values (14.0 +/- 5.0 vs. 9.6 +/- 3.7 pmol/L; P less than 0.01). There was no significant difference in thyroid function between the patients with Graves' disease with positive and negative TPII index values. TPII appears to inhibit thyroid function in some patients, but no simple relationship between TPII and thyroid function in autoimmune thyroid disease was demonstrated. Understanding the factors that control access of anti-TPO antibody to its antigen may help to elucidate the significance of circulating anti-TPO antibody. PMID- 2921309 TI - Metabolism of [3H]equilin-[35S]sulfate and [3H]equilin sulfate after oral and intravenous administration in normal postmenopausal women and men. AB - The absorption of equilin sulfate and equilin from the gastrointestinal tract was determined in normal men after the ingestion of [3H]equilin-[35S]sulfate or a mixture of [3H]equilin and equilin-[35S]sulfate, while the metabolism of equilin sulfate was investigated after iv administration of [3H]equilin sulfate to postmenopausal women. After the oral administration of [3H]equilin-[35S]sulfate, equilin sulfate containing both 3H and 35S was isolated from plasma; however, only in the first sample taken at 10 min was the 3H/35S ratio the same as that of the [3H]equilin-[35S]sulfate ingested. The 3H/35S ratio then increased, and by 12 h only traces of equilin-[35S]sulfate were detectable. Similarly, after the ingestion of [3H]equilin and equilin-[35S]sulfate, [3H]equilin-[35S]sulfate was isolated from plasma. The 3H/35S ratio was at all time points greater than the 3H/35S ratio of the ingested mixture. Analysis of urine indicated that over 98% of 35S was not associated with any steroid and was most likely inorganic sulfate. After iv administration of [3H] equilin sulfate to postmenopausal women, equilin, equilenin, 17 beta-dihydroequilin, and 17 beta-dihydroequilenin were isolated from the urine. These results indicate that 1) some of the orally administered equilin sulfate was absorbed from the gut without prior hydrolysis, 2) some equilin sulfate was hydrolyzed in the gut before absorption; 3) equilin was absorbed more efficiently than equilin sulfate; 4) equilin absorbed was readily sulfated and circulated in this form; and 5) equilin sulfate was extensively metabolized, and the metabolites were excreted in the urine mainly conjugated with glucuronic acid. PMID- 2921310 TI - Thyroid peroxidase and thyroid microsomal autoantibodies. AB - The antithyroid microsomal antibodies found in the serum of patients with autoimmune thyroid disease are directed largely, if not entirely, against thyroid peroxidase (TPO). In this study we used a highly purified, well characterized, large tryptic fragment of porcine TPO (hereafter referred to as purified porcine TPO) to examine possible differences among microsomal antibodies in patients with autoimmune thyroid disease. Antibodies against this TPO preparation and also against a synthetic peptide corresponding to residues 780-793 of the deduced sequence of the native enzyme were compared with microsomal antibodies from patients in immunoblot experiments. The antiporcine TPO and antisynthetic peptide antibodies reacted with crude preparations of human TPO. Binding of serum microsomal antibodies to purified porcine TPO was also found. Purified porcine TPO shows two fragments after gel electrophoresis under reducing conditions: a 59K fragment corresponding to the amino end of the molecule, and two approximately 30K fragments corresponding to the carboxyl end. Using an immunoblot procedure with purified porcine TPO as the antigen, we found that at least two epitopes were involved in microsomal antibody production: one associated with the 59K fragment and the other with the approximately 30K fragment(s). The distribution of serum antibodies against these epitopes differed among the patients, indicating that these antibodies comprise a heterogeneous group. Serum from patients with autoimmune thyroid disease significantly inhibited human TPO activity, raising the possibility that microsomal antibodies may contribute to the impaired thyroid function that occurs in some patients with autoimmune thyroid disease. PMID- 2921311 TI - Hormonal manipulation of endometrial maturation. AB - Three experimental protocols were devised to induce endometrial maturation in 12 women with ovarian failure. Each was planned to serve a dual purpose: to resolve a particular clinical situation related to synchronization between ovum donor and recipient and to answer a specific question about endometrial physiology. A fourth protocol of sequential estrace (2-6 mg/day) and progesterone (P4; 25-50 mg/day, im) simulating the 28-day natural cycle, served as a control protocol (18 cycles). A short follicular phase protocol consisted of only 6 days of estrogen (E) administration before addition of P4 (13 cycles). In the long follicular phase protocol (5 cycles), estrace was given for 3-5 weeks, and P4 administration was accordingly postponed. In 6 accelerated secretory transformation cycles, 150 mg/day P4 were administered, im, from day 15 onward. The adequacy of the induced endometrial cycles was evaluated by hormonal, morphological, and histochemical criteria relevant to endometrial normalcy and receptivity. Serum estradiol levels and the areas under the estradiol curves for the long and short follicular phase protocols differed significantly from those during the control cycles (P less than 0.005). Areas under the estradiol curves in the accelerated secretory transformation protocol yielded significantly higher P4 values than those in all other protocols (P less than 0.05). All biopsies in the 3 experimental protocols compared favorably with those of the control protocol. Glycocalyx intensity (periodic acid-Schiff) and the amount of galactose residues in the glycocalyx (Ricinus communis-I agglutinin) were greatest during the periimplantation interval. We conclude that a very short exposure of the human endometrium to E or, conversely, prolonged E stimulation will allow normal endometrial maturation with the addition of P4. Supraphysiological doses of P4 in the accelerated secretory transformation protocol significantly enhanced endometrial maturational processes. PMID- 2921312 TI - Estrogen replacement decreases the set point of parathyroid hormone stimulation by calcium in normal postmenopausal women. AB - Estrogens decrease serum total and ionized calcium (Ca) concentrations in postmenopausal women with or without primary hyperparathyroidism, but cause little or no increase in serum PTH suggesting a modification of the relationship between the two. In order to define this relationship, we studied the effect of conjugated estrogens on total and ionized serum Ca and serum PTH concentrations in five normal postmenopausal women, before and after 3, 11, and 23 weeks of therapy. Dynamic tests of parathyroid gland function, based on 2-h iv infusions of CaCl2 and NaEDTA, were performed at each time. Total and ionized serum Ca and carboxylterminal PTH were measured every 15 min during the infusions, and parathyroid function was evaluated by a nonlinear 4-parameter mathematical model. Estrogen therapy caused decreases in serum total [2.36 +/- 0.04 (SD) mmol/L, baseline vs. 2.19 +/- 0.05 mmol/L, 23 weeks, P less than 0.005) and ionized calcium (1.27 +/- 0.01 mmol/L, baseline vs. 1.21 +/- 0.02 mmol/L, 23 weeks, P less than 0.005]; the decreases were evident at 3 weeks and persisted for the duration of the study. Serum PTH concentrations did not change (8.94 +/- 1.84 pmol/L, baseline vs. 8.98 +/- 2.38 pmol/L, 23 weeks). Three parameters of the parathyroid function, the maximal response to hypocalcemic stimulation, the nonsuppressible fraction of circulating PTH, and the slope of PTH on calcium at the set point were not affected by estrogen treatment. The fourth parameter, the set point of PTH stimulation by serum total calcium (2.16 +/- 0.04 mmol/L, baseline vs. 1.97 +/- 0.07 mmol/L, 23 weeks, P less than 0.0166) or by serum ionized Ca (1.19 +/- 0.04 mmol/L, baseline vs. 1.12 +/- 0.03 mmol/L, 23 weeks, P less than 0.01), was decreased by estrogen treatment. This was evident at the earliest time point studied and persisted thereafter. The decrease in ionized Ca set point only explained 40% of the decrease in total calcium set point, the remaining 60% being related to hemodilution of plasma protein during therapy. We conclude that estrogen replacement can influence parathyroid function in postmenopausal women by resetting the set point of PTH stimulation by ionized Ca. This in turn could contribute to the estrogen-induced changes in their Ca balance. PMID- 2921313 TI - Neurohypophyseal secretion in response to cholecystokinin but not meal-induced gastric distention in humans. AB - Exogenous administration of cholecystokinin octapeptide (CCK) is known to decrease food intake and slow gastric emptying in humans and animals. Recent studies have shown that CCK stimulates neurohypophyseal secretion of oxytocin (OT) in rats and arginine vasopressin (AVP) in monkeys, and that gastric distention also stimulates OT release in rats. We therefore studied AVP and OT secretion in 14 normal subjects in response to meal-induced gastric distention and administration of CCK, both separately and in combination, to assess whether these stimuli similarly activated central neurohypophyseal pathways in humans. Neither plasma AVP nor OT concentrations increased after gastric distention produced by ingestion of a large meal. However, a dose-related increase in plasma AVP, but not OT levels, occurred after CCK administration, the threshold CCK dose being 0.05 micrograms/kg body weight. The AVP secretion in response to CCK administration was significantly correlated with subjective aversive symptoms quantified by use of a numeric scale (r = 0.61, P less than 0.001). In 12 of the 14 subjects plasma AVP levels increased in association with symptoms of epigastric pressure and discomfort before the onset of overt nausea or emesis. The combination of CCK and meal-induced gastric distention did not stimulate increases in plasma AVP levels in excess of those produced by CCK administration alone. The results demonstrate that AVP secretion resulting from emetic center activation often is a graded response that can begin in association with milder degrees of visceral discomfort before symptoms of overt nausea or emesis. In addition, the stimulation of AVP secretion by CCK administration, but not by meal induced gastric distention in association with physiological satiety, suggests that some component of the anorectic effects of exogenous CCK in man likely results from activation of brainstem emetic centers. PMID- 2921314 TI - Resistance to 1,25-dihydroxyvitamin D3 of cultured psoriatic epidermal keratinocytes isolated from involved and uninvolved skin. AB - 1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3], a hormonally active form of vitamin D3, has been reported to stimulate epidermal differentiation and to be an effective treatment of psoriatic lesions. We studied the responsiveness of psoriatic epidermal keratinocytes to 1,25-(OH)2D3 in explant-outgrowth cultures of involved and uninvolved skin from six patients with psoriasis. A feeder layer was required for outgrowth of psoriatic epidermal keratinocytes of involved skin, but not for that of cells of uninvolved skin. The growth of normal epidermal keratinocytes was inhibited by 1,25-(OH)2D3, and the number of DNA-synthesizing cells, determined in autoradiographs, was reduced to about 15% of that in control cultures by 1 nmol/L 1,25-(OH)2D3 (0.4 ng/mL). Epidermal keratinocytes isolated from both involved and uninvolved skin of patients with psoriasis were resistant, and 100-fold more 1,25-(OH)2D3 was required to inhibit their DNA synthesis. These results afford new insight into the etiology and therapy of psoriasis. PMID- 2921315 TI - Globin gene expression in erythroid human fetal liver cells. AB - We measured steady-state levels of the human globin mRNAs in liver samples from several mid-gestational fetuses. RNA from the epsilon, gamma, beta, zeta, theta, and alpha globin genes were present in fetal liver samples isolated from 10-25-wk embryos. The abundance of all human globin mRNAs declined in older fetuses, presumably because of a gradual reduction in the proportion of erythroid precursors in the liver as development proceeds. The gamma:beta globin mRNA ratio in 10-18-wk fetal erythroblasts was 6-7:1, and in adult erythroid bone marrow the ratio was 0.02:1. In fetal liver samples, the relative abundance of epsilon transcripts was less than 1% that of gamma, and zeta transcripts less than 5% that of alpha. Embryonic transcripts declined in abundance during late fetal development and were not detected in newborn liver or adult erythroid bone marrow. theta globin mRNA also represented a minor species (less than 1% that of alpha) in fetal liver samples, but in contrast to the embryonic mRNAs, was most abundant in adult marrow samples obtained from patients with erythroid hyperplasia. These results support the hypothesis that globin protein levels are regulated by the relative amounts of each globin mRNA at various stages of erythropoietic development. PMID- 2921316 TI - Stimulus-induced critical point. Mechanism for electrical initiation of reentry in normal canine myocardium. AB - The hypothesis was tested that the field of a premature (S2) stimulus, interacting with relatively refractory tissue, can create unidirectional block and reentry in the absence of nonuniform dispersion of recovery. Simultaneous recordings from a small region of normal right ventricular (RV) myocardium were made from 117 to 120 transmural or epicardial electrodes in 14 dogs. S1 pacing from a row of electrodes on one side of the mapped area generated parallel activation isochrones followed by uniform parallel isorecovery lines. Cathodal S2 shocks of 25 to 250 V lasting 3 ms were delivered from a mesh electrode along one side of the mapped area to scan the recovery period, creating isogradient electric field lines perpendicular to the isorecovery lines. Circus reentry was created following S2 stimulation; initial conduction was distant from the S2 site and spread towards more refractory tissue. Reentry was clockwise for right S1 (near the septum) with top S2 (near the pulmonary valve) and for left S1 with bottom S2; and counterclockwise for right S1 with bottom S2 and left S1 with top S2. The center of the reentrant circuit for all S2 voltages and coupling intervals occurred at potential gradients of 5.1 +/- 0.6 V/cm (mean +/- standard deviation) and at preshock intervals 1 +/- 3 ms longer than refractory periods determined locally for a 2 mA stimulus. Thus, when S2 field strengths and tissue refractoriness are uniformally dispersed at an angle to each other, circus reentry occurs around a "critical point" where an S2 field of approximately 5 V/cm intersects tissue approximately at the end of its refractory period. PMID- 2921317 TI - Relationship between whole plasma calcitonin levels, calcitonin secretory capacity, and plasma levels of estrone in healthy women and postmenopausal osteoporotics. AB - The exact role of calcitonin (CT) in the pathogenesis of postmenopausal osteoporosis remains unknown. Whole plasma calcitonin (iCT) basal levels, metabolic clearance rate (MCR), and production rate (PR) of CT were measured in 9 premenopausal and 16 postmenopausal women, including 11 osteoporotics (OP). Basal iCT levels were statistically lower in postmenopausal women than in the premenopausal group (P less than 0.01) and strongly correlated (r = 0.72; P less than 0.001) with estrone circulating levels (E1). MCR were similar in all groups. PR were similar in eugonadal women between 22 (mean +/- SD = 30.9 +/- 9.9 micrograms/d) and 37 yr (mean +/- SD = 25.5 +/- 11.1 micrograms/d) premenopausal women. In healthy postmenopausal women PR were reduced, but not significantly (mean +/- SD = 19.5 +/- 6.95 micrograms/d), whereas osteoporotic patients presented a highly significant reduction of CT PR (mean +/- SD = 9.8 +/- 4 micrograms/d) (P less than 0.01). Because there is a strong relationship between E1 and PR (r = 0.64; P less than 0.001), CT secretory capacity appears to be modulated by estrogen circulating levels. This modulation leads to a menopause related decrease in iCT. In osteoporotics, an independent impairment of CT production drastically lowers PR and basal iCT levels. CT might be one of the determining factors in the pathogenesis of postmenopausal osteoporosis. PMID- 2921318 TI - Transforming growth factor beta regulates thyroid growth. Role in the pathogenesis of nontoxic goiter. AB - The production and growth regulatory activity of transforming growth factor beta were studied in human thyroid tissue. As estimated by its mRNA expression in fresh tissue samples, transforming growth factor beta was produced in normal and in diseased thyroid glands. Transforming growth factor beta mRNA was mainly produced by thyroid follicular cells and in lesser quantities by thyroid infiltrating mononuclear cells. The concentrations of transforming growth factor beta mRNA were lower in iodine-deficient nontoxic goiter than in Graves' disease and normal thyroid tissue. Transforming growth factor beta protein secretion by cultured thyroid follicular cells was also low in nontoxic goiter, but could be increased by addition of sodium iodide (10 microM) to the culture medium. Recombinant transforming growth factor beta did not affect basal tritiated thymidine incorporation in cultured thyroid follicular cells, but inhibited, at a concentration of 10 ng/ml, the growth stimulatory influence of insulin-like growth factor I, epidermal growth factor, transforming growth factor alpha, TSH, and partly that of normal human serum on cultured thyroid follicular cells. This inhibition was greater in Graves' disease than in nontoxic goiter. These results suggest that transforming growth factor beta may act as an autocrine growth inhibitor on thyroid follicular cells. Decreased transforming growth factor beta production and decreased responsiveness to transforming growth factor beta may be cofactors in the pathogenesis of iodine-deficient nontoxic goiter. PMID- 2921319 TI - Peroxisomal bifunctional enzyme deficiency. AB - Peroxisomal function was evaluated in a male infant with clinical features of neonatal adrenoleukodystrophy. Very long chain fatty acid levels were elevated in both plasma and fibroblasts, and beta-oxidation of very long chain fatty acids in cultured fibroblasts was significantly impaired. Although the level of the bile acid intermediate trihydroxycoprostanoic acid was slightly elevated in plasma, phytanic acid and L-pipecolic acid levels were normal, as was plasmalogen synthesis in cultured fibroblasts. The latter three parameters distinguish this case from classical neonatal adrenoleukodystrophy. In addition, electron microscopy and catalase subcellular distribution studies revealed that, in contrast to neonatal adrenoleukodystrophy, peroxisomes were present in the patient's tissues. Immunoblot studies of peroxisomal beta-oxidation enzymes revealed that the bifunctional enzyme (enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase) was deficient in postmortem liver samples, whereas acyl-CoA oxidase and the mature form of beta-ketothiolase were present. Density gradient centrifugation of fibroblast homogenates confirmed that intact peroxisomes were present. Immunoblots of fibroblasts peroxisomal fractions showed that they contained acyl-CoA oxidase and beta-ketothiolase, but bifunctional enzyme was not detected. Northern analysis, however, revealed that mRNA coding for the bifunctional enzyme was present in the patient's fibroblasts. These results indicate that the primary biochemical defect in this patient is a deficiency of peroxisomal bifunctional enzyme. It is of interest that the phenotype of this patient resembled neonatal adrenoleukodystrophy and would not have been distinguished from this disorder by clinical study alone. PMID- 2921320 TI - Chronic exercise training protects aged cardiac muscle against hypoxia. AB - To test the hypothesis that chronic exercise may improve tolerance to hypoxia in aged hearts, we compared cardiac function of exercised rats to that of their age matched, nonexercised controls. Right ventricular papillary muscles were removed from young adult (9 mo) and old (24-26 mo) male Fischer 344 rats that were chronically exercised on a rodent treadmill and from their age-matched, nonexercised controls. During isometric contraction, hypoxia depressed contraction and relaxation in all muscles, but to a lesser extent in the exercised groups. A significant exercise effect was observed in the following variables: the maximum developed tension, the maximum rate of tension development, the maximum rate of tension decline, and the time required for the hypoxia to reduce maximum tension by 20%. The maximum rate of tension decline was more sensitive to hypoxia than was the maximum rate of tension development in all groups. Exercise also had an effect on the temperature dependence of cardiac performance during hypoxia. Thus, chronic exercise results in the preservation of both contraction and relaxation during hypoxia for aged as well as young adult hearts. PMID- 2921321 TI - Collagen gene expression by cultured human skin fibroblasts. Abundant steady state levels of type VI procollagen messenger RNAs. AB - Previous studies have suggested that procollagen types I and III are the major collagenous gene products of cultured human skin fibroblasts. In this study the expression of 10 different genes, encoding the subunit polypeptides for collagen types I-VI, by human skin fibroblasts in culture was analyzed by molecular hybridizations. Northern transfer analysis demonstrated the presence of specific mRNA transcripts for collagen types I, III, IV, V, and VI, but not for type II collagen. Quantitation of the abundance of these mRNAs by slot blot hybridizations revealed that type I, III, and VI procollagens were the major collagenous gene products of skin fibroblasts in culture. The mRNAs for type IV and V collagens represented only a small percentage of the total collagenous mRNA transcripts. Further analysis by in situ hybridization demonstrated that the majority of the cultured cells coexpressed the genes for type I, III, and VI procollagen pro-alpha chains. Further in situ hybridization analyses revealed the expression of type VI collagen genes in normal human skin. These data demonstrate that human skin fibroblast cultures can be used to study the transcriptional regulation of at least nine genetically distinct procollagen genes. The data further suggest that type VI collagen, in addition to types I and III, may be a major collagenous component of human skin. PMID- 2921322 TI - Cutaneous xanthoma in association with paraproteinemia in the absence of hyperlipidemia. AB - In the present report we describe a patient with multiple myeloma and long standing paraproteinemia who developed xanthoma in the absence of an elevation in plasma cholesterol or triglyceride concentrations. Studies demonstrated that our patient's monoclonal IgG antibody interacted with apoprotein B-100. The LDL antibody complex isolated from our patient did not affect the degradation of LDL by human fibroblasts, indicating that while IgG derived from our patient interacted with LDL it did not alter the metabolism of this lipoprotein by the LDL receptor pathway. Since the LDL receptor pathway is the major route of LDL metabolism, this probably explains why our patient was not hyperlipidemic. In contrast to an absence of effect on the LDL receptor, our patient's LDL-antibody complex stimulated cholesterol esterification within macrophages indicating the uptake and degradation of the LDL-antibody complex. The LDL-antibody complex inhibited the degradation of acetyl LDL by macrophages (scavenger pathway), demonstrating that our patient's LDL-antibody complex was recognized as a modified LDL. Moreover, mixing Ig from our patient with normal LDL also resulted in the normal LDL increasing the esterification of cholesterol by macrophages. One can hypothesize that our patient's monoclonal IgG-LDL complex interacted with the macrophage scavenger receptor, thereby resulting in the occurrence of xanthoma in the absence of hyperlipidemia. PMID- 2921323 TI - Characterization of aldosterone-induced potassium secretion in rat distal colon. AB - The role of apical and basolateral membranes in aldosterone-induced active potassium (K) secretion in rat distal colon was investigated by measuring mucosal to-serosal (Jms) and serosal-to-mucosal (Jsm) 42K fluxes (mueq.h-1.cm-2) across isolated stripped mucosa under short-circuit conditions in normal and secondary hyperaldosterone animals. In normal colons mucosal tetraethylammonium (TEA; 30 mM) or barium (Ba; 5 mM), but not cesium (Cs; 15 mM), reduced Jsm without affecting Jms. In aldosterone animals (a) net K secretion (-0.54 +/- 0.11) was converted to net K absorption (0.63 +/- 0.15) by mucosal TEA, which produced a marked reduction in Jsm (0.82 +/- 0.07) and an increase in Jms (0.35 +/- 0.07). In contrast mucosal Ba resulted in a relatively smaller reduction in JK(sm) without altering JK(ms), whereas mucosal Cs was ineffective; (b) serosal bumetanide or the removal of serosal Na or Cl markedly inhibited JK(sm and abolished net K secretion; and (c) serosal ouabain (1 mM) produced qualitatively similar effects to those of serosal bumetanide. These results demonstrate that (a) normal rat distal colon contains apical TEA- and Ba-sensitive K channels; (b) aldosterone induces TEA-sensitive and Ba-sensitive apical K channels; (c) aldosterone-induced K secretion requires both the Na,K-pump and Na-K-2Cl cotransport for K uptake across the basolateral membrane; and (d) alteration of any of these processes results in inhibition of aldosterone-induced active K secretion simultaneously with stimulation of K absorption. PMID- 2921324 TI - Macrophage phagocytosis of aging neutrophils in inflammation. Programmed cell death in the neutrophil leads to its recognition by macrophages. AB - Mechanisms governing the normal resolution processes of inflammation are poorly understood, yet their elucidation may lead to a greater understanding of the pathogenesis of chronic inflammation. The removal of neutrophils and their potentially histotoxic contents is one prerequisite of resolution. Engulfment by macrophages is an important disposal route, and changes in the senescent neutrophil that are associated with their recognition by macrophages are the subject of this investigation. Over 24 h in culture an increasing proportion of human neutrophils from peripheral blood or acutely inflamed joints underwent morphological changes characteristic of programmed cell death or apoptosis. Time related chromatin cleavage in an internucleosomal pattern indicative of the endogenous endonuclease activation associated with programmed cell death was also demonstrated. A close correlation was observed between the increasing properties of apoptosis in neutrophils and the degree of macrophage recognition of the aging neutrophil population, and a direct relationship between these parameters was confirmed within aged neutrophil populations separated by counterflow centrifugation into fractions with varying proportions of apoptosis. Macrophages from acutely inflamed joints preferentially ingested apoptotic neutrophils and histological evidence was presented for occurrence of the process in situ. Programmed cell death is a phenomenon of widespread biological importance and has not previously been described in a cell of the myeloid line. Because it leads to recognition of intact senescent neutrophils that have not necessarily disgorged their granule contents, these processes may represent a mechanism for the removal of neutrophils during inflammation that also serves to limit the degree of tissue injury. PMID- 2921325 TI - Purification of a distinct placental lactogen receptor, a new member of the growth hormone/prolactin receptor family. AB - Recent findings from this laboratory suggest that the biological actions of placental lactogen (PL) in mammalian fetal tissues are mediated through binding of the hormone to a distinct and unique PL receptor. We have now purified this receptor from fetal and maternal sheep liver, characterized its binding to PL, growth hormone (GH), and prolactin (PRL), and determined its molecular weight by SDS-PAGE and by affinity cross-linking techniques. Soluble extracts containing specific, high-affinity (Kd 0.5 nM) PL binding activity were prepared by incubating ovine fetal and maternal liver microsomes with 1% Triton X-100. The detergent solubilized PL receptor was purified two- to threefold by ion-exchange chromatography and an additional twofold by gel exclusion chromatography on Sepharose 6B. The PL receptor was then purified 75,000- to 125,000-fold by affinity chromatography using a column of ovine PL (oPL) coupled to Affi-Gel 10. The molecular weight of the oPL receptor as determined by SDS-PAGE and by cross linking techniques was 44,000 +/- 2,000 (range 40,000-48,000). The purified receptor bound 125I-oPL specifically and with high affinity (Kd 0.5 nM) but did not bind either radiolabeled ovine GH or ovine PRL. In addition, in competition studies using 125I-oPL as the radioligand, the purified PL receptor bound unlabeled oPL with a potency 30-50 times greater than that of ovine GH and 500 1,000 times greater than that of ovine PRL. These findings demonstrate the presence of a specific PL receptor in fetal and maternal sheep liver. The PL receptor, together with the GH and PRL receptors, constitute a family of distinct but related hormone receptors that differ in their relative affinities for PL, GH, and PRL. Changes in the expression of the three receptors may mediate changes in the hormonal control of growth during the transition from fetal to postnatal life. PMID- 2921326 TI - Prophylaxis of early ventricular fibrillation by inhibition of acylcarnitine accumulation. AB - Hypoxia in isolated myocytes results in accumulation of long-chain acylcarnitines (LCA) in sarcolemma. Inhibition of carnitine acyltransferase I (CAT-I) with sodium 2-[5-(4-chlorophenyl)-pentyl]-oxirane-2-carboxylate (POCA) prevents both the accumulation of LCA in the sarcolemma and the initial electrophysiologic derangements associated with hypoxia. Another amphiphilic metabolite, lysophosphatidylcholine (LPC), accumulates in the ischemic heart in vivo, in part because of inhibition of its catabolism by accumulating LCA. It induces electrophysiologic alterations in vitro analogous to early changes induced by ischemia in vivo. The present study was performed to determine whether POCA could prevent accumulation of both LCA and LPC induced by ischemia in vivo and if so, whether attenuation of early arrhythmogenesis would result. LAD coronary artery occlusions were induced for 5 min in chloralose-anesthetized cats. Coronary occlusion in untreated control animals elicited prompt, threefold increases of LCA (73 +/- 8 to 286 +/- 60 pmol/mg protein) and twofold increase of LPC (3.3 +/- 0.4 to 7.5 +/- 0.9 nmol/mg protein) selectively in the ischemic zone, associated with ventricular tachycardia (VT) or ventricular fibrillation (VF) occurring within the 5-min interval before acquisition of myocardial samples in 64% of the animals. POCA prevented the increase of both LCA and LPC. It also prevented the early occurrence of VT or VF (within 5 min of occlusion) in all animals studied. The antiarrhythmic effect of POCA was not attributable to favorable hemodynamic changes or to changes in myocardial perfusion measured with radiolabeled microspheres. Thus, inhibition of CAT-I effectively reduced the incidence of lethal arrhythmias induced early after the onset of ischemia. Accordingly, pharmacologic inhibition of this enzyme provides a promising approach for prophylaxis of sudden cardiac death, that typically occurs very soon after the onset of acute ischemia, in man. PMID- 2921327 TI - Effects of acetazolamide on Na+-HCO-3 cotransport in basolateral membrane vesicles isolated from rabbit renal cortex. AB - We evaluated the effects of acetazolamide on Na+-HCO3- cotransport in basolateral membrane vesicles isolated from the rabbit renal cortex. Na+ uptake stimulated by an imposed inward HCO3- gradient was not significantly reduced by 1.2 mM acetazolamide, indicating that acetazolamide does not directly inhibit Na+-HCO3- cotransport. 4,4'-Diisothiocyanostilbene-2,2'-disulfonate (DIDS)-sensitive Na+ base cotransport was found to be absolutely CO2/HCO3--dependent. We therefore tested whether acetazolamide-sensitive availability of HCO3- at the basolateral membrane could be rate-limiting for Na+-base cotransport under some conditions. In the presence of a CO2/HCO3- buffer system but absence of an initial HCO3- gradient, Na+ influx was stimulated fivefold by an outward NH4+ gradient. This stimulation of Na+ influx by an outward NH4+ gradient was inhibited greater than 75% by 0.6 mM acetazolamide, suggesting that acetazolamide blocked the ability of the NH4+ gradient to generate an inward HCO3- gradient. In the presence of an inward HCO3- gradient, Na+ influx was inhibited greater than 70% by an inward NH4+ gradient. This inhibition of Na+ influx was reduced to only 35% by 0.6 mM acetazolamide, suggesting that acetazolamide blocked the ability of NH4+ to collapse the inward HCO3- gradient. Similarly, Na+ influx in the presence of an inward HCO3- gradient was inhibited greater than 80% by an outward acetate gradient, and this inhibition was reduced to only 50% by acetazolamide. Thus, acetazolamide caused either inhibition or stimulation of Na+ uptake depending on the conditions with respect to pH and HCO3- gradients. The indirect interaction of acetazolamide with the basolateral membrane Na+-HCO3- cotransport system may be an important mechanism underlying inhibition of proximal tubule acid secretion by this agent. PMID- 2921328 TI - Electrophysiologic characteristics of sudden QRS axis deviation during orthodromic tachycardia. Role of functional fascicular block in localization of accessory pathway. AB - We analyzed the effect of functional fascicular block (FFB) on ventriculoatrial conduction time (VACT) during orthodromic tachycardia (OT) in 32 patients with single accessory pathway (AP) of the Kent bundle type. The location of AP was left free wall (LFW-AP) in 21 patients, left posteroseptal in 6, right free wall in 2, and right anteroseptal in 3. FFB either alone or in combination with functional left or right bundle branch block (LBBB or RBBB) occurred predominantly at the onset of OT and was initiated with ventricular extrastimulus technique more often than with atrial extrastimulation. In patients with LFW-AP, isolated functional left anterior fascicular block (LAFB) produced significant prolongation in VACT (15-35 ms). A similar magnitude of VACT increase (20-35 ms) was also observed when LAFB was associated with RBBB. Although 25-45-ms prolongation in VACT occurred with functional LBBB and normal axis, an additional 20-55-ms VACT increase was seen when LAFB accompanied LBBB. Functional LAFB, alone or in combination with bundle branch block, however, did not prolong VACT in patients with other AP locations. Furthermore, left posterior fascicular block did not produce prolongation of VACT in any of the cases. It is concluded that in patients with the Wolff-Parkinson-White syndrome, evaluation of VACT during functional LAFB provides important information regarding AP localization and a clear separation of LFW-AP from all other locations. PMID- 2921330 TI - A modification of the sagittal splitting technique ensuring that the osteotomy split lies immediately medial to the lateral cortex. AB - A modification of Obwegeser's sagittal splitting method for the correction of mandibular prognathism has been developed. The anterior border of the proximal segment is partially removed at the beginning of osteotomy, which is carried out on the immediate inner surface of the lateral cortex. This osteotomy plane just under the lateral cortex, obtained by the use of a thin, disposable reciprocating sawblade, contributed to a lower incidence of postoperative lower lip hypaesthesia in the 14 cases presented. PMID- 2921329 TI - Functional effects on glomerular hemodynamics of short-term chronic cyclosporine in male rats. AB - We evaluated the effects of chronic cyclosporine (CsA) administration on the determinants of nephron filtration rate (SNGFR) using micropuncture techniques (mp) in male Munich-Wistar rats. Animals received CsA (30 mg/kg SQ) in olive oil daily for 8 d before mp. Controls (PFC) were pair fed. SNGFR, glomerular capillary hydrostatic pressure gradient (delta P), nephron plasma flow (SNPF), plasma protein oncotic pressure (pi A), and glomerular ultrafiltration coefficient (LpA) were quantitated in each experiment. CsA was associated with a lower SNGFR due to decreases in SNPF and a major reduction in delta P but no decrease in LpA. Plasma volume expansion (PVE) caused SNGFR, delta P, and SNPF to increase in both CsA and PFC without eliminating the differences between CsA and PFC. CsA/PVE rats responded normally to angiotensin II (AII) infusion indicating that the low delta P associated with CsA is not due to unresponsiveness to AII. Prior renal denervation caused SNGFR and SNPF to increase in CsA-treated animals but failed to alter the reduction in glomerular capillary pressure after CsA or to eliminate the glomerular hemodynamic differences between treated animals and pair-fed controls. This constellation of glomerular hemodynamic abnormalities suggests that the renal effect of short-term chronic CsA administration is mediated primarily by a reduction in the afferent effective filtration pressure resulting from an imbalance between pre- and postglomerular vascular resistances. PMID- 2921331 TI - Malar bone fractures and their sequelae. A statistical study of 1.393 cases covering a period of 20 years. AB - The authors analyse the results of 1.393 cases of malar fractures treated in the maxillo-facial Departments of Montpellier and Perpignan. A clinical and therapeutic classification is given. Study of the sequelae demonstrated that the most frequent were infra-orbital nerve lesions, residual displacement of the malar bone, diplopia, and enophthalmos. A point is made about the use of Franchebois's inflatable balloon as a means of retention. Its indications as well as its contra-indications are clearly defined. The reduction in the number of bone sequelae, when compared to cases treated without the balloon, demonstrates the efficacy and simplicity of this method. PMID- 2921332 TI - Mandibular invasion by oral squamous cell carcinoma. AB - Forty-five specimens consisting of mandibular bone and adjacent squamous cell carcinoma were histologically investigated. In 23 of them, there was no involvement of the mandibular bone: a continuous periosteal layer separated the tumour from the bone. Tumour spread through periosteal lymphatics was not observed in any of these cases and therefore there is no reason to sacrifice bone when the tumour is not fixed to the jaw. Twenty-two specimens exhibited bony involvement. In 10 of them, the bone was eroded by an advancing tumour front. None of these cases exhibited tumour invasion into cancellous spaces, dental canal or periodontal ligament space. Tumours with this type of bony involvement are amenable to mandible-sparing surgical treatment. The other 12 exhibited diffuse growth into cancellous bone, dental canal and, if present, periodontal ligament space. Cases like these are to be operated on by removing the entire thickness of the involved mandibular part. Tumours involving bone were slightly larger than those leaving bone uninvolved. The tumours eroding bone were of a smaller size than those infiltrating bone. The differences, however, are too small to have a predictive value in treatment planning. Attention is drawn to the presence of dental epithelial rests that should not be mistaken for invading tumour nests. PMID- 2921333 TI - Mandibular reconstruction with the THORP condylar prosthesis after hemimandibulectomy. AB - The subject of this paper is the evaluation of the advantages pertaining to the THORP (titanium hollow screw reconstruction plate) condylar prosthesis for reconstruction after hemimandibulectomy and exarticulation. The THORP condylar prosthesis is three-dimensionally adjustable, enabling the intraoperative meticulous functional adaptation of the condyle. Various designs of the condyle make it possible to achieve optimal congruency between the articular fossa and condyle. The anchorage of the prosthesis to the stump of the mandible is achieved with perforated hollow-screws rigidly fixed to the plate, thus producing optimal functional stability. The long-term follow-up of eleven cases, reconstructed with this system, confirmed the correct guidance and functional efficiency of this type of condylar prosthesis. PMID- 2921334 TI - Ornithine-vasopressin gangrene and reconstruction of the upper lip. Case report. AB - A bilateral cleft lip and palate case received ornithine-vasopressin intra operatively in preparation for a vasoconstricted field of the various lip segments prior to the repair of the cleft lip. A cyanotic tinge appeared immediately. This eventually led to total necrosis of the upper lip. Various relevant blood tests were done and a mild thrombocytosis was found. Surgical reconstruction of the upper lip was performed by means of a forked cross-lip flap -the main blood supply coming from the columella--as well as by means of an inferiorly pedicled cheek flap from the para-nasal area. PMID- 2921335 TI - Necrotizing fasciitis of the middle third of the face. A case report. AB - A 48-year-old man with necrotizing fasciitis in the right middle third face is presented. The patient had uncontrolled diabetes mellitus and liver cirrhosis. The condition was controlled by early diagnosis, prompt surgical management and adjunctive broad spectrum antibiotic cover after entering hospital, the curettage of the necrotizing tissue of the right cheek was especially effective. PMID- 2921336 TI - United Kingdom external quality assessment in blood coagulation: the first 21 years. PMID- 2921337 TI - False positive bromide partition test in lymphomatous meningitis. PMID- 2921338 TI - Neutrophil elastase and elastic tissue in emphysema. PMID- 2921339 TI - Death certification: increased clinical confidence in diagnosis and lack of interest in confirmation by necropsy is not justified. AB - Comparison of 742 necropsies from 1975 with 833 from 1984 showed that the degree of certainty the clinicians attached to their diagnosis of the underlying cause of death had increased significantly in 1984. This was due almost exclusively to an increase in the certainty of the diagnosis of circulatory disease. Unfortunately, this was not justified as the numbers of false positive and false negative diagnoses were high in both years. With this increased certainty came a lack of interest in the necropsy. Similar lack of interest was also shown by surgeons in 1984, though in this instance it was accompanied by a high level of agreement between their diagnoses and necropsy findings. PMID- 2921340 TI - Fatal head injury in children. AB - A comprehensive neuropathological study was undertaken on 87 children aged between 2 and 15 years with fatal head injuries to identify those features which occurred at the time of head injury (fractured skull, contusions, intracranial haematoma and diffuse axonal injury) and those which were subsequently produced by complicating processes (hypoxic brain damage, raised intracranial pressure, infection and brain swelling). The types of brain brain damage identified were remarkably similar to those seen in adults. The only difference was the prevalence of diffuse brain swelling in children. PMID- 2921341 TI - Fine needle aspiration of thyroid nodules: three years' experience. AB - To overcome the difficulties arising in the management of cold nodules of the thyroid--many are unnecessarily resected because of the risk of malignancy--fine needle aspiration cytology was used in the assessment of thyroid lesions in 113 patients. Aspirates were categorised into three groups as follows: group (i), consistent with simple goitre or cyst; group (ii), suspicious of underlying cellular lesion or tumour; group (iii), malignant. Resections for simple goitre were reduced from eight of 14 (40%) to two of 42 (3%) over three years, and the yield of neoplastic lesions coming to surgery as a result of aspiration increased from two of 12 (16%) to nine of 14 (69%) over the same period. It is concluded that fine needle aspiration cytology is an effective means of discriminating between simple and neoplastic thyroid lesions. This permits more appropriate patient management and a beneficial saving of resections for simple goitre. False negative diagnoses (two cases) in our series are of more concern than false positive results, but can be minimised by careful attention to sampling and cytological detail. PMID- 2921342 TI - Proliferative activity in endometrial stromal granulocytes throughout menstrual cycle and early pregnancy. AB - The proliferative activity in endometrial stromal granulocytes was studied using two approaches. Firstly, mitotic activity was studied in paraffin wax embedded sections of normal non-pregnant endometrium and early pregnancy decidua stained with phloxine-tartrazine. Secondly, the monoclonal antibody Ki67 was applied to cryostat sections of similar tissues. Endometrial stromal granulocytes were identified by their labelling with NKH1, Dako T11, UCHL1 or Dako-LC. The percentage of cases in which endometrial stromal granulocytes showed mitosis was 25%, 75%, 86%, and 93%, respectively in proliferative, early secretory, mid secretory, and late secretory phases, and 14% in early decidua. There were at most one or two endometrial stromal granulocytes in mitosis per 10 high power fields. Double labelled cells were present in small numbers in proliferative endometrium and in moderate numbers in secretory endometrium. Only a few cells in early decidua double labelled with Ki67/T11; moderate numbers of cells double labelled with Ki67/Dako-LC. It is concluded that proliferative activity does occur in endometrial stromal granulocytes and is particularly prominent in the late secretory phase. PMID- 2921343 TI - Statistics on microcomputers: a non-algebraic guide to their appropriate use in biomedical research and pathology laboratory practice. 4. Correlation and regression. PMID- 2921344 TI - Serum placental-like alkaline phosphatase (PLAP): a novel combined enzyme linked immunoassay for monitoring ovarian cancer. AB - A new combined enzyme linked immunoassay (ELISA) was developed to measure both serum placental-like alkaline phosphatase (PLAP) activity (PLAPA) and concentration (PLAPC) in the same microtitre plate using an Imperial Cancer Research Fund monoclonal antibody, designated H17E2. PLAP A and PLAP C were determined together with an existing marker, CA125 in 397 serial samples from 87 patients with epithelial ovarian cancer. Retrospective assessment showed the sensitivity to increase from 73% with CA125 alone, to 88% using CA125 and PLAP A, and to 93% with all three markers in 261 samples from the patients with known active disease at the time of sampling. When the results for all 397 samples were included in the analysis, however, the specificity, sensitivity, accuracy and predictive powers of this monoclonal antibody were not sufficiently high to assist in the prospective follow up of patients with ovarian cancer. This was due to a significant number of false positive and false negative results. Our data indicate that PLAP A or PLAP C estimation with H17E2 may, therefore, only be of value in the management of those patients with known active disease who are already known to be "marker positive" for this antigen. PMID- 2921345 TI - N-myc gene product expression in neuroblastoma. AB - The presence and distribution of N-myc gene product were studied in 13 neuroblastomas and five ganglioneuroblastomas, using immunohistochemical techniques. Nine tumors (eight neuroblastomas and one ganglioneuroblastoma of composite type) contained neuroblastoma cells with positive nuclei for N-myc protein. Microscopic examination showed that most of the positive neuroblastoma cells seemed to be immature, with no apparent neuronal differentiation. Nine of 11 tumours with amplified N-myc gene copies exhibited tumour cells with positive immunostaining for the N-myc gene product, while none of the seven non-N-myc amplified cases contained immunoreactive tumour cells. The survival of the patients positive for N-myc protein was significantly low compared with that of the negative ones. It is concluded that immunohistochemical staining for the N myc gene product will facilitate prediction of the prognosis of patients with neuroblastoma. PMID- 2921346 TI - Primary acquired sideroblastic erythropoiesis in non-anaemic and minimally anaemic subjects. AB - Six patients had primary sideroblastic erythropoiesis together with a haemoglobin concentration of 12.0 g/dl or higher. In four cases this was associated with macrocytosis. Other abnormalities included failure of erythroid progenitor growth from peripheral blood in three cases and occasional dysplastic appearances in neutrophils and megakaryocytes. Sideroblastic erythropoiesis seems to be an early manifestation of the myelodysplastic syndrome and may present clinically at a pre anaemic stage. PMID- 2921347 TI - Tolerance to penicillin in streptococci of viridans group. AB - Tolerance to penicillin was investigated in 40 isolates of optochin-resistant, alpha-haemolytic streptococci. Thirteen strains exhibited tolerance to penicillin (MBC:MIC ratio greater than or equal to 32) when stationary phase inocula were used, but only seven strains retained the tolerance phenotype in experiments with logarithmic phase inocula. There was a striking association between tolerance and Eagle's optimum dosage effect, particularly among strains that displayed tolerance in both the stationary and the logarithmic growth phases. Sequential viable counts on representative strains showed that reliance on the arbitrary criterion of bactericidal activity of 99.9% reduction of the original inoculum after 24 hours' exposure may occasionally lead to difficulties in the recognition of penicillin tolerance. In general, however, the 99.9% killing criterion provided a useful discriminator between strains that were rapidly killed by penicillin and those (tolerant strains) in which the bactericidal activity was much reduced. PMID- 2921348 TI - ACP Broadsheet 120: January 1989. Guide to diagnosis of inborn errors of metabolism in district general hospitals. PMID- 2921349 TI - Effect of international sensitivity index (ISI) of thromboplastins on precision of international normalised ratios (INR) AB - The contribution of the thromboplastin international sensitivity index (ISI) to the interlaboratory coefficient of variation (CV) of the international normalised ratio (INR) with individual reagents was assessed. In theory the precision of the INR should increase with lower ISI values. An empirical relation has been established between the ISI, the INR, and its CV for two rabbit thromboplastins used in sufficient numbers for analysis in the United Kingdom. This was based on the cumulative data from the United Kingdom National External Quality Assessment Scheme (NEQAS) surveys over two years beginning in 1986. The actual precision achieved in NEQAS for the two reagents depends on the ISI value of the thromboplastin and it agreed closely with the figure predicted by the empirical model. The findings show that the ISI value of a thromboplastin strongly influences the interlaboratory variability of the INR obtained with it. The CV of the INR approximates to the CV of the prothrombin ratio multiplied by the ISI. Manufacturers of thromboplastin should therefore be encouraged to produce reagents showing good precision of results reported as simple prothrombin ratios and a low ISI value to avoid impairment in precision when ratio results are transformed to INR. PMID- 2921350 TI - Effect of automation on prothrombin time test in NEQAS surveys. AB - The performance of coagulometers in the National Quality Assessment Scheme (NEQAS) surveys of the prothrombin time conducted between 1986 and 1987 was reviewed. There were sufficient data for analysis for eight types of coagulometer used with a single type of thromboplastin reagent and one instrument with an alternative reagent. The overall reliability efficacy of each instrument was evaluated by determining the orthogonal regression slope parameters for prothrombin time (PT) and international normalised ratios (INR) using the manual technique as the reference method. Seven of the eight types of coagulometer tended to overestimate the INR. A pattern frequently observed with coagulometers, and difficult to regulate, was a trend to underestimate INR below 3.0 and overestimate higher INR. Overestimation of INR values over 3.0 was particularly pronounced with three types of instrument (Fibrintimer, Lancer, KC4/10). The KC4/10 was used by a sufficient number of participants to permit analysis of the performance of individual instruments. Within instrument differences were similar to those produced by different types of coagulometers. Thromboplastin reagents affected the INR values obtained with coagulometers. The study indicates that each local reagent-instrument combination must be calibrated by the participant to obtain reliable INR values. The use of a general correction factor for a local PT system seems to be invalid owing to the considerable variation in performance of individual coagulometers. The two best guides to the choice of coagulometer may be the deviation from the manual result and precision estimated by the coefficient of variation of the INR. PMID- 2921351 TI - Statistics on microcomputers. A non-algebraic guide to the appropriate use of statistics packages in biomedical research and pathology laboratory practice. 5. Analysis of categorical data. PMID- 2921352 TI - Aspergillosis of the nose and paranasal sinuses. AB - Fulminant aspergillosis was diagnosed on nasal biopsy in a 49 year old man who had features of an aspergilloma. Further postmortem examination of this area was performed and the results were contrasted with the histological features of other Aspergillus infections. The nasal biopsy specimen and postmortem examination showed infiltrating Aspergillus hyphae with tissue necrosis and little inflammatory response. The hyphae were easily seen with routine stains. This contrasts with the findings in invasive aspergillosis where there is fibrosis and a granulomatous response to the Aspergillus hyphae. The hyphae are seen in giant cells using fungal stains. In the saprophytic infections aspergilloma and allergic Aspergillus sinusitis there is no tissue invasion or destruction. Aspergillus infections of the nose and paranasal sinuses often require biopsy for accurate diagnosis. As treatment varies pathologists need to be able to distinguish the different patterns of infection. PMID- 2921353 TI - Campylobacter-like organisms and heterotopic gastric mucosa in Meckel's diverticula. AB - To assess the possibility that Campylobacter pylori might colonise heterotopic gastric mucosa a detailed histological review of 69 cases of Meckel's diverticula resected over 17 years was undertaken. Twenty three were resected incidentally while 46 were excised as the suspected cause of symptoms. Gastric mucosa was found in 13 diverticula (19%), 10 from the symptomatic group and three from the incidental cases, of which eight showed active gastritis affecting the heterotopic mucosa. Specific staining showed spiral bacteria with the typical morphology of C pylori adherent to gastric mucosa in four of the diverticula showing active gastritis. Campylobacter-like organisms were not seen on normal heterotopic gastric mucosa or on adjacent intestinal epithelium. The findings show that Campylobacter-like organisms, identical in appearance, staining, and distribution with C pylori, colonise and possibly inflame heterotopic gastric mucosa in Meckel's diverticulum. PMID- 2921354 TI - Comparison of clinical and postmortem diagnosis of pulmonary embolism. AB - The incidence of pulmonary embolism and the number of clinically missed diagnoses of it in necropsies carried out between 1960 and 1984 at this department were investigated. Pulmonary embolism primarily affects elderly people with serious underlying disease; in this study it was found more often in women. The incidence of pulmonary embolism (9% of all necropsies) was unchanged during the period studied. In contrast, pulmonary embolism as the "sole" cause of death increased (p less than 0.0005). Although most pulmonary emboli were the immediate cause of death, the clinical diagnosis was often missed (in 84% of all cases). Furthermore, such clinically missed diagnoses increased over the years (p less than 0.005), especially in patients with heart disease and cancer. Without necropsy there will be considerable underdiagnosis of pulmonary embolism, therefore providing a misleading figure in the death statistics for this often fatal disease. PMID- 2921355 TI - The binding of peroxidase-labelled lectins to human endometrium in normal cyclical endometrium and endometrial adenocarcinoma. AB - The nature of endometrial glycoconjugates throughout the menstrual cycle was investigated using a panel of lectins directed against specific sugar groups. This approach was also applied to a series of endometrial adenocarcinomas the findings for which were compared with those of normal controls. A change in the expression of glycosubstances was found in relation to the phase of the menstrual cycle; that there was increasing sialylation of terminal galactose groups during the secretory phase. This change may be influenced by progesterone. One group of endometrial adenocarcinomas exhibited binding patterns similar to those seen in secretory endometrium and this may be related to progesterone receptor state. Expression of fucose containing glycosubstances was identified in half of the carcinomas but not in the normal control tissue, thus indicating that a change in fucosylation occurs with endometrial neoplasia. None of the lectin binding patterns, however, correlated with variables in the patients themselves or within the tumours. PMID- 2921356 TI - C-myc oncogene product P62c-myc in ovarian mucinous neoplasms: immunohistochemical study correlated with malignancy. AB - The monoclonal antibody Myc 1-6E10 was used to determine the cellular distribution of the c-myc oncogene product p62c-myc in 60 mucinous ovarian tumours. Three patterns of immunostaining were apparent: (i) nuclear staining alone; (ii) staining of the nucleus and basal cytoplasm; and (iii) staining of the entire cell. Of the 21 cases of mucinous cystadenoma, 11 showed nuclear staining alone, and a further case showed additional weak staining of the basal cytoplasm. Nuclear staining alone was not present in any of the 17 borderline mucinous tumours examined. Strong staining of the nucleus and basal cytoplasm was seen in 16 of these borderline cases, six of which also showed focal staining of the apical cytoplasm. All 22 cases of mucinous cystadenocarcinoma showed staining of the cell nucleus and entire cell cytoplasm. Focal staining of the apical cytoplasm in six of 17 borderline mucinous tumours produced a pattern of c-myc immunostaining similar to that of cystadenocarcinoma. Retrospective analysis of the clinical data showed that no significant differences between patients with borderline tumours of these two categories could be defined. Although immunostaining with Myc 1-6E10 can be used in the categorisation of mucinous ovarian tumours, it is concluded that standard histological criteria are more accurate indicators of tumour behaviour than is an assessment of c-myc expression. PMID- 2921357 TI - Association between invasiveness, inflammatory reaction, desmoplasia and survival in colorectal cancer. AB - Five hundred and twenty seven colorectal carcinomas were reviewed histologically. A multivariate analysis (Cox) was used to test the prognostic importance of certain histological features (invasiveness, inflammatory reaction, and amount of fibrous tissue) at the tumour edge after allowance had been made for clinicopathological stage, tumour site, and histological type and grade. A poorly defined tumour border, lack of inflammatory reaction, and a pronounced fibrosis (desmoplasia) at the tumour edge were associated with unfavourable stage distributions, but each of these features also had an independent effect on prognosis. PMID- 2921358 TI - Pseudohyponatraemia, hypercholesterolaemia, and primary biliary cirrhosis. AB - A 62 year old woman with primary biliary cirrhosis was found to have a plasma sodium concentration of 115 mmol/l. Follow up showed this to be a "pseudohyponatraemia" due to a massively raised serum cholesterol concentration of 78 mmol/l. Electrophoresis of serum lipoproteins and of the lipoproteins and apolipoproteins in fractions isolated on density-gradient ultracentrifugation showed that the major portion of the serum cholesterol was being transported with lipoprotein-X. Low density lipoprotein-cholesterol concentration was also raised. Lipoprotein-X contained, in addition to albumin and apolipoprotein C, apolipoprotein E. This case is of interest because of the degree of hypercholesterolaemia, its association with pseudohyponatraemia, and the unequivocal demonstration of apolipoprotein E associated with lipoprotein-X. PMID- 2921359 TI - Diurnal variations in serum biochemical and haematological measurements. AB - Twenty five biochemical and haematological measurements were determined on nonfasting blood and serum samples collected between 9 am and 7 pm from a representative group of 7685 British middle-aged men. Most measurements showed significant diurnal variations, but only for bilirubin, phosphate, and triglyceride did time of day account for more than 5% of the between subject variance. Serum bilirubin concentrations showed a pronounced downward trend in the afternoon, the mean value after 6 pm being 30% lower than the mean value in the morning. Mean serum triglyceride and phosphate concentrations increased steadily through the day. Mean concentrations of potassium, haemoglobin, and haematocrit and red cell count were higher in the morning, while urea and creatinine concentrations and white cell count had higher means in the afternoon. Glucose showed a pattern consistent with short term response to meals. The effects of these diurnal trends on routine use of biochemical tests needs careful consideration, and a greater understanding of their biological mechanisms is required. PMID- 2921360 TI - Quantitation of lactoferrin in odontogenic cyst fluids. AB - A competitive enzyme linked immunosorbent assay (ELISA) method was used to measure the concentration of lactoferrin in fluids from 36 odontogenic keratocysts, 15 dentigerous cysts, and 30 radicular/residual cysts. Keratocyst fluids contained significantly higher concentrations of lactoferrin than fluids from the other two types of cyst (p less than 0.001); but the range of values obtained within each group was large. Although lactoferrin represents a larger proportion of the total protein in keratocyst fluids than in dentigerous or radicular cyst fluids, lactoferrin concentration is not an absolute diagnostic marker for keratocysts. Lactoferrin concentration correlated strongly with the numbers of neutrophils present in keratocyst fluids (p less than 0.001), less so for dentigerous cyst fluids (p less than 0.05, and not at all in the case of radicular cyst fluids. It is suggested that neutrophils are the source of lactoferrin in the three categories of cyst studied but that the relatively impermeable nature of the keratocyst lining probably accounts for the particularly high concentrations of lactoferrin found in their fluids. Given that most keratocysts were asymptomatic, acute inflammation itself does not explain the reason for the high numbers of neutrophils in many of the fluids. PMID- 2921361 TI - Discrepant toxoplasma latex agglutination test results. AB - The analysis of 4450 toxoplasma serology results showed that 59 (1.3%) latex agglutination reactions were not confirmed in the dye test. These discrepant results were associated with an unspecified IgM antibody but not associated with kit batch variation, inactivation of sera, concurrent cytomegalovirus infection, or the presence of hepatitis B virus "e" antigen. The latex agglutination test is useful as a screen for toxoplasma infection but false positive reactions do occur. Patients at risk of severe toxoplasmosis should be investigated by additional tests. PMID- 2921362 TI - False positive latex tests negative by ELISA for toxoplasma IgG. AB - An enzyme linked immunosorbent assay (ELISA) kit for detecting IgG class antibody to T gondii was compared with the latex agglutination test to determine the specificity as a screening method in 12 patients who had undergone heart transplantation (recrudescence of T gondii infection n = 3, donor acquired infection n = 3; acute cytomegalovirus infection n = 6). The latex agglutination test detected antibodies to primary T gondii infection much earlier in the infection than the ELISA, but the ELISA method was useful for detecting previous infection. It is concluded that the ELISA technique is more complex to perform than the latex agglutination test but the use of IgM and IgG assays combined could reduce the number of samples sent to the reference laboratory and thus reduce the time taken to obtain a final result. PMID- 2921363 TI - Biotin-labelled antigen screening test for toxoplasma IgM antibody. AB - A method for the simple preparation of biotin-labelled toxoplasma antigen was used with avidin peroxidase in an IgM-capture enzyme linked immunosorbent assay (BAM-ELISA). Although the overall predictive value of a positive result was only 38%, its low cost and 100% sensitivity makes it a very suitable screening test. Positive results can be confirmed by an alternative assay, thus providing a more economical and effective diagnostic service than either screening all sera by a commercial test or selecting sera for IgM testing. PMID- 2921364 TI - Comparison of two bone trephine instruments used for quantitative histomorphometry. AB - Transilial bone samples were obtained at necropsy using trephine instruments with internal diameters of 2 mm and 7 mm. Undecalcified histological sections were prepared and two structural histomorphometric variables (percentage of trabecular bone volume and surface density of bone) were estimated by a Quantimet 720 image analyser. The differences between the variables measured from the two adjacent cores were due to differences in biopsy site rather than the size of the sample. The smaller diameter needle is therefore recommended for use as the biopsy procedure is simpler and tissue sections can be prepared sooner than is the case with the larger needle. PMID- 2921365 TI - Tightly spiral shaped bacteria in gastric antrum: are they urease positive? PMID- 2921366 TI - Sensitivity of Campylobacter pylori to colloidal bismuth subcitrate. PMID- 2921367 TI - Enterotoxin production by strains of Staphylococcus aureus isolated from clinical specimens. PMID- 2921368 TI - Nucleolar organiser regions in squamous tumours of the pharynx and larynx. PMID- 2921369 TI - Hypercalcaemia in Hodgkin's disease without hyperparathyroidism or skeletal metastases. PMID- 2921370 TI - Comparative longitudinal study of 2 methods of scheduling maintenance visits: 4 year data. AB - 116 subjects were recruited from a population of patients previously treated for adult periodontitis and maintained in periodontal health by means of periodic prophylaxes every 3-6 months. The subjects were divided into a control (C) and a test (T) group. A total of 33 patients in the T group and 47 in the C group completed the 4-year study. The C subjects were examined every 6 months and given a prophylaxis every 3 months. The patients in the T group were examined at similar intervals, but prophylaxes were administered according to the individualized scheme of Listgarten and Shiffter, on the basis of a differential microscopic count of subgingival bacterial morphotypes. Recurrent periodontitis was defined as an increase in probing depth of 3 mm or more from baseline measurements. Teeth so affected were sampled microbiologically when the diagnosis of recurrent disease was made and "exited" from the study for treatment. A control microbial sample was taken at the same time from a previously-defined pooled sample of non-affected surfaces with comparatively high, but stable probing depths. During a 4-year period, more than half of the subjects developed at least one recurrence of disease, and one-third of the subjects had 2 or more recurrences of periodontitis. Disease recurred on approximal surfaces 81% and on orovestibular surfaces 19% of the time. There were no significant differences in the rate of disease recurrence between the C and the T group, even though recall intervals in the T group at the 4-year examination averaged 19.4 months and an average of 30.6 months had elapsed since the previous prophylaxis. Both groups exhibited similar plaque index and gingival index scores, similar probing depth and attachment level measurements, and similar proportions of different bacterial morphotypes during the 4-year study. However, differences were noted between examinations for both groups with respect to most of these criteria. This study provides 4-year longitudinal data on the clinical and certain microbiological characteristics of a population of adult patients previously treated for moderate to advanced periodontitis, and subsequently placed on periodontal maintenance. The results indicate that some of these patients may remain in good periodontal health despite the lack of regular tri-monthly recall visits, and that microscopic monitoring of the subgingival microbiota may be of value in identifying these individuals.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2921371 TI - Effects of subgingival irrigation on A. actinomycetemcomitans. AB - The effects of repeated subgingival irrigation on Actinobacillus actinomycetemcomitans was examined. 24 periodontal pockets harboring A. actinomycetemcomitans in 3 juvenile and 4 adult periodontitis patients were studied. The protocol included bi-weekly subgingival irrigation with hydrogen peroxide of the periodontal sites until the micro-organism was no longer detected by selective culture, or for 6 months. A. actinomycetemcomitans was gradually suppressed to below detection following the irrigation regime and could no longer be detected in 46% of the sites at completion of the irrigation protocol. The sites were microbiologically re-examined 5 months after cessation of the irrigation regime. A. actinomycetemcomitans re-occurred in only 2 of the sites from which it had originally been suppressed below detection. The results indicate: (1) that the irrigation regime tested has some potential to suppress A. actinomycetemcomitans in periodontal pockets; (2) that the effect of the irrigation protocol generally lasted for 5 months; (3) that the reduction rate of A. actinomycetemcomitans to below detectable levels seems related to the initial number of cultivable bacteria from the periodontal pocket. PMID- 2921372 TI - The impact of regression towards the mean on probing changes in studies on the effect of periodontal therapy. AB - The purpose of this report was to evaluate the magnitude of the regression towards the mean (RTM) relative to the observed changes in probing measurements following periodontal therapy in 2 groups of patients. Regression lines were calculated for observed changes in probing depths and probing attachment levels related to the initial probing depths of the individual sites. Regression lines, adjusted for the RTM effect, were also calculated. For the extreme subgroups of recorded shallow and deep sites, the RTM effect (mm) was found to amount to a maximum of 0.6 mm. It appears unlikely that erroneous conclusions have been made in previous clinical studies evaluating probing depth changes in deep sites, since the RTM accounts for a limited portion of the observed changes. For probing depth changes in shallow sites and for probing attachment level changes in both shallow and deep sites, the RTM accounts for a larger proportion of the observed mm changes. It therefore seems prudent to be careful about interpretation of these changes in clinical studies, where the RTM effect has not been adjusted for. Whenever possible, duplicate initial recordings should be taken to allow determination of and subsequent adjustment for the RTM effect. PMID- 2921373 TI - A retrospective radiographic study of alveolar bone loss in the primary dentition in patients with localized juvenile periodontitis. AB - Lately, it has been questioned whether localized juvenile periodontitis (LJP) is restricted to the permanent dentition, or if it sometimes might have a prepubertal onset, involving the primary dentition. To clarify this question, 17 patients with LJP, together with 17 non-LJP matched controls, were retrospectively examined for radiographic signs of alveolar bone destruction in their primary dentitions. All LJP subjects but one showed localized marginal bone loss, whereas no bone loss was observed among the controls. The results suggest that at least some cases of LJP start in the primary dentition prior to the involvement of the permanent teeth. PMID- 2921375 TI - Microbiological aspects of diseases. PMID- 2921374 TI - Metronidazole plus amoxycillin in the treatment of Actinobacillus actinomycetemcomitans associated periodontitis. AB - The potential use of an adjunctive therapy of metronidazole plus amoxycillin for the subgingival elimination of Actinobacillus actinomycetemcomitans in periodontitis patients was investigated. 22 patients participated in this study, 11 with localized juvenile periodontitis (LJP) and 11 with rapidly progressive periodontitis (RPP). 14 patients had received periodontal treatment in the past. All patients were subgingivally infected with A. actinomycetemcomitans. After mechanical subgingival debridement in combination with the antibiotic treatment, elimination of A. actinomycetemcomitans was achieved in all patients but one. With this one exception, clinical improvements were observed in all patients, resulting in reduced pocket probing depths as well as in a significant reduction in bleeding on probing. Re-examination of 16 patients after 9-11 months revealed that A. actinomycetemcomitans was still undetectable and further clinical improvement was observed. It was concluded that the combination of metronidazole plus amoxycillin is a valuable adjunct to mechanical therapy in A. actinomycetemcomitans associated periodontal infections. PMID- 2921376 TI - A 1-year study on the maintenance of gingival health by a dentifrice containing a zinc salt and non-anionic antimicrobial agent. AB - An experimental dentifrice containing zinc citrate and Triclosan was used by student nurses for 12 months without supervision, while a corresponding group used a control dentifrice. Dental flossing was not permitted during the first 6 months. Gingival health achieved in a pre-experimental period, during which oral hygiene instruction was given, was maintained by users of the experimental dentifrice for 12 months but not by users of the control dentifrice. About 1/3 of the control group used floss daily during the 2nd 6 months and significantly improved their gingival health to a level comparable to that of the experimental group. Flossing brought no extra benefit for the latter group. In the control group, approximal regions were less healthy than buccal or lingual sites. The gingival health of these sites improved significantly with daily flossing. The experimental dentifrice maintained gingival health in all sites irrespective of the use of floss. The study has confirmed that oral health can be maintained by the use of the experimental dentifrice for at least 12 months in a habitual toothbrushing regime, and that the dentifrice would be as effective and simpler than relying on the combination of brushing and regular flossing. PMID- 2921377 TI - Relationships between alveolar bone levels measured at surgery, estimated by transgingival probing and clinical attachment level measurements. AB - Alveolar bone level measurements obtained by transgingival probing were compared with alveolar bone levels measured during surgery at 178 sites in 9 patients. Probing depth measurements using constant loads of 30 g and 60 g were also compared with bone levels measured at surgery at the above sites. The effects of inflammation, location of the site on the tooth surface and tooth type were also investigated. Transgingival probing was unaffected by these factors and proved to be an accurate method of measuring alveolar bone levels (r = 0.975). Probing depth measurements were affected by the presence of inflammation, assessed by the bleeding response to probing, and variation in probing load. The effect of inflammation was to reduce the mean distance between the probe tip and the alveolar bone from 2.4 mm to 1.9 mm. None of the relationships between the measurements were significantly affected by the location of the site on the tooth surface, or by tooth type. PMID- 2921378 TI - Odontogenic epithelial hamartomas in periodontal structures. AB - 4 hamartomas apparently derived from remnants of the dental lamina and enamel organ are reported in a collection of human jaw specimens. These epithelial lesions represent a transitional stage between a developmental anomaly and a distinct odontogenic neoplasm. Earlier reports indicated that such lesions with clinical symptoms are rare; however, this study suggests a more common occurrence on a microscopic level. PMID- 2921379 TI - Citric acid burnishing of dentinal root surfaces. A scanning electron microscopy report. AB - The integrity of formalin-fixed periodontally diseased root surfaces was assessed following root planing to dentin and citric acid application. Extracted human teeth (fixed in 10% formalin), with crowns removed, were vertically sectioned in half. A horizontal groove on each proximal surface marked the extent of attachment loss. The diseased root surface was vigorously root planed to expose dentin. Cotton pellets, soaked in a saturated solution of citric acid, were either "placed" (control) or "burnished" (vigorously rubbed using root planing pressure) (experimental) on the prepared root surface for 5 min. Pellets were changed 2 times/min. The teeth were fixed and prepared for scanning electron microscope viewing and photography. A representative print was selected for each specimen. To confirm differences between test and control groups, untrained raters were asked to perform 2 sorting exercises. First, they were asked to sort the representative photographs of each specimen into 2 piles based on surface characteristics. Second, they were asked to choose from pairs of photographs, representing matched specimens, the one photograph which appeared to have the greatest collagen surface area. The surfaces of experimental specimens revealed patent dentinal tubules and an intertubular area with a very distinct "shag carpet" appearance of deeply tufted collagen fibrils. Control samples also exhibited open dentinal tubules, yet the intertubular surface displayed a "matted collagen" surface. Results of the 2 sorting exercises confirm that burnishing of formalin-fixed dentin root surfaces for 5 min with cotton pellets soaked in a saturated solution of citric acid consistently produces a distinct tufted collagen fibril surface.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2921380 TI - Neural hyperplasia is not a diagnostic prerequisite in nodular prurigo. A controlled morphometric microscopic study of 26 biopsy specimens. PMID- 2921381 TI - Pilomatricoma associated with epidermoid cyst. AB - The clinical and pathological features of 4 cases of pilomatricoma associated with epidermoid cysts, are described. None of the cases showed features of Gardner's syndrome. PMID- 2921382 TI - Scrotal calcinosis. PMID- 2921383 TI - Morphometrical analysis of mycosis fungoides on paraffin-embedded sections. AB - Morphometry was carried out on H&E stained paraffin sections of 29 cases of contact dermatitis (CD) and 35 cases of mycosis fungoides (MF) (patch stage 12; plaque stage 11; tumor stage 12); 9 nuclear parameters, mean thickness of the infiltrate and 5 stereological parameters were assessed for each slide. Application of a non-parametric discriminant analysis (k-nearest neighbour method) which is based on median of nuclear areas, mean maximal nuclear diameter, volume density and numerical density of nuclei provided discrimination between CD and patch stage MF at an efficiency of 82.9% (specifity 86.7%, sensitivity 61.5%). Efficiency of discrimination between CD and plaque stage was 92.5% (specifity 89.7%, sensitivity 91.7%) and between CD and tumor stage 100% when discriminant analysis was based on the mean thickness of the infiltrate. Although unequivocal discrimination between CD and MF cannot be achieved in each individual case, morphometry on routine paraffin material obviously provides additional objective criteria for the diagnosis of early MF. PMID- 2921384 TI - A survey of reference accuracy in five national dental journals. AB - Previous studies have examined the bibliographic accuracy of citations in medical journals. The purpose of this study was to assess reference accuracy in five national dental journals. One hundred references were randomly selected from the March, 1987, issue of each of five dental journals (a total of 500 references). Each reference was verified either from the original source or from other indexing tools if the original was unavailable. References were divided into two categories: incorrect and correct. The number of incorrect references was counted and subdivided into major and minor errors. The errors were grouped by types of error: author, article title, citation (which included errors in journal title, volume, issue, and page numbers), and "unable to verify". This survey found 211 (42%) inaccuracies out of 500 references reviewed, with a total of 248 errors within the incorrect group. Out of the latter, 173 (70%) were minor errors, and 75 (30%) were major errors. Types of minor errors ranked as follows: minor article title errors, 86 (35%); minor author errors, 61 (25%); and minor citation errors, 26 (10%). Types of major errors were ranked as follows: incorrect journal citation, 32 (13%); "unable to verify", 25 (10%); incorrect author, 10 (4%); and incorrect article title, 8 (3%). The results of this survey showed that nearly half of the references reviewed were inaccurate. PMID- 2921385 TI - A modified DDE Index for use in epidemiological studies of enamel defects. AB - The aim of this study was to investigate possible modifications to the DDE Index to make it simpler to use and to make the data collected more meaningful and amenable to analyses and interpretation. After the use of the DDE Index in a National Study in Ireland, initial alterations to the Index were tested on a group of children with enamel defects, in Ireland and New Zealand. The DDE Index was then modified to allow for the measurement of demarcated, diffuse, and hypoplastic defects and their severity. With the Modified Index, the prevalence of defects both on index teeth and all permanent tooth surfaces of 8- and 15-year old children in fluoridated Cork City and non-fluoridated areas of Cork County and Manchester, U.K., was measured. The prevalence of enamel defects on one or more index teeth of children in the three areas ranged from 30 to 42% in 8-year olds and from 31 to 38% in 15-year-olds. The percentage of children affected as seen by full-mouth examination was somewhat higher, ranging from 38 to 51% for 8 year-olds and 58 to 63% for 15-year-olds. The percentage of index teeth affected (7 to 14%) was generally higher than for all teeth (5 to 9%). Demarcated opacities were the most common defect seen. Diffuse opacities were found to be the discriminating factor between the fluoridated and non-fluoridated areas. In all areas, the vast majority of diffuse opacities extended over less than 1/3 of the surface area of the teeth affected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2921386 TI - Increased pH-lowering ability of Streptococcus mutans cell masses associated with extracellular glucan-rich matrix material and the mechanisms involved. AB - Streptococcus mutans strain IB-1600 was cultivated in Todd-Hewitt broth (THB) or THB supplemented with sucrose (S). Cell mass obtained from THB exhibited a high cell density and negligible glucan-rich extracellular matrix material (EMM), whereas cell mass from 2% S-supplemented THB exhibited widely-spaced cells separated by EMM. The pH-lowering potential of the different cell masses was studied in vivo with an intra-oral enamel demineralization test and rinsing with glucose solution, and in vitro with a model which permits vertical penetration of glucose through the cell mass and pH evaluation at different depths within the cell mass. In vivo, the pH profile of EMM-rich cell mass derived from 2% S supplemented THB was characterized by a lower pH minimum and a slower return of the pH as compared with THB-derived cell mass. In vitro, an increase in cell mass EMM content was associated with a more rapid initiation and an increase in the rate of pH drop in the depth of the cell masses. Evaluation of the acidogenic potential of the cells in cell masses derived from THB and 2% S-supplemented THB with suspensions of dispersed cell mass and added glucose indicated no difference. The buffering capacity of cell mass derived from 2% S-supplemented THB within the pH range of 6.5-4.0 was greatly reduced as compared with that of THB-derived cell mass, due to the relatively low buffering capacity of EMM. The presence of EMM also appeared to enhance the porosity of the cell mass.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2921387 TI - Prevention of sucrose-induced demineralization of tooth enamel by chewing sorbitol gum. AB - Measurements were made of the effect of chewing sorbitol gum on the intra-oral demineralization induced by rinsing with 10% sucrose solutions. Blocks of bovine enamel were covered with a layer of Streptococcus mutans IB1600, and mounted on palatal appliances that were worn by five subjects for defined periods of time. Enamel demineralization was determined by following changes in iodide penetrability (delta Ip) of the enamel surfaces. Delta Ip increased to a maximum of about 15 units between 30 and 45 min, while the pH of the S. mutans plaque dropped to below 4 by 15 min. Plaque pH returned to 4.9 by 60 min. Chewing sorbitol gum after the sucrose rinse minimized further increases in delta Ip and brought about a more rapid return of the S. mutans plaque pH toward neutrality. The effect of chewing gum was greater when chewing was initiated earlier so that, when gum was given at five min after the sucrose rinse, demineralization was only 37% of that obtained without gum. The findings confirm earlier reports on the effect of gum on plaque pH, and directly demonstrate the profound protective effects that chewing sorbitol gum can have on tooth enamel. PMID- 2921388 TI - The effects of pellicle formation on streptococcal adhesion to human enamel and artificial substrata with various surface free-energies. AB - The influence of a pellicle on streptococcal adhesion was studied. A "ripened" two-hour salivary pellicle and an "early" five-minute salivary pellicle were formed on human enamel and artificial solid substrata with varying surface free energies. Three strains of oral streptococci, also with widely different surface free-energies, were used for adhesion studies. Pellicle formation and streptococcal adhesion took place at a constant shear rate of 21 s-1. Adhesion of S. mitis BMS to bare and pellicle-covered enamel was low and not significantly affected by the presence of a pellicle (0.7 x 10(6) and 0.6 x 10(6) cells.cm-2, resp.), whereas the numbers of S. sanguis 12 and S. mutans NS adhering to bare enamel (4.2 x 10(6) cells.cm-2 and 13.8 x 10(6) cells, cm-2, resp) were significantly reduced by the presence of a pellicle. This reduction was almost complete after only five minutes of salivary protein adsorption (1.9 x 10(-6) and 1.1 x 10(6) cells.cm-2 for S. sanguis and S. mutans, resp.) but further reduced for S. sanguis adhering to a ripened pellicle (0.7 x 10(6) cells.cm-2). The numbers of streptococci adhering at equilibrium to bare enamel could be fitted to a thermodynamically based model, which was previously described for bacterial adhesion to homogenous artificial substrata. Streptococcal adhesion to artificial substrata exposed to saliva was low, and the differences among uncoated materials were markedly reduced even after only five minutes' exposure to saliva. PMID- 2921389 TI - A new method for the estimation of mutans streptococci in human saliva. AB - A new method for quantitating the numbers of mutans streptococci in saliva--the "Strip mutans" test--was developed. It includes the following steps: A prepared plastic spatula is contaminated with saliva, transferred to a selective broth, incubated for two days, and dried. A predetermined area is counted or evaluated for CFUs of mutans streptococci. The medium contains sucrose to promote adhesion of mutans streptococci to the strip. Bacitracin, added just before use, is the basis for the selectivity. Results with the new medium were compared with those from the "spatula technique" and with those from conventional saliva sampling with dilution. The studies involved 302 and 60 schoolchildren, respectively. There was a highly significant correlation between the results from the new method and those from conventional methods. The strip mutans test is easy to used and has long shelf-life, and the spatulas with adherent colonies can be saved for future comparisons. PMID- 2921390 TI - Curing light-activated composite cement through porcelain. AB - The purpose of the study was to determine the exposure times needed to harden a light-activated composite cement through various thicknesses of porcelain. A negative exponential model was developed with which the relative hardness of a composite could be predicted from the product of the exposure time and the square root of the light intensity at 470 nm. Hardness data obtained by varying the exposure time and porcelain thickness were found to fit this model. A relationship was derived to predict the required exposure time, t, of a composite under porcelain with a transmission coefficient, Tc, and a thickness, l:t = toTc 1/2, where to is the exposure time of the composite alone. PMID- 2921391 TI - Mechanical properties of poly(alkyl alpha-fluoroacrylate)s as denture-base materials. AB - alpha-Fluoro-substituted acryl polymers, poly(methyl alpha-fluoroacrylate) (PMFA) and poly(2,2,2-trifluoroethyl alpha-fluoroacrylate) (P3FFA) were investigated for extension to denture-base resins. PMFA, in which fluorine attaches to the polymer chain, had excellent mechanical properties: For instance, compressive and bending strength and bending modulus were 50% higher than those of PMMA. P3FFA, in which fluorines are substituted at the end of the pendant alkyl ester, showed poor mechanical properties. Contrary to expectations, the amount of water sorption of PMFA was about twice that of PMMA, while that of P3FFA was almost zero. Copolymers of MFA and 3FFA were prepared in an attempt to optimize the mechanical properties and the water sorption. The copolymer with 40% of 3FFA showed higher compressive, diametral tensile, and bending strength; in particular, the bending modulus and water resistance were about 35% and 20% higher, respectively, than those of PMMA. Improvement of the mechanical properties and increase of the water sorption of PMFA may be due to intermolecular forces induced by polarizability of the fluorine and carboxy group along the polymer chain. Decrease of the water sorption by fluorine substituted on the alkylester group as in P3FFA may be due to higher hydrophobicity and steric effect of the fluoroalkyl substitute. PMID- 2921392 TI - Oligomers with pendant isocyanate groups as adhesives for dentin and other tissues. AB - Oligomers containing pendant isocyanate groups were synthesized from various vinyl monomers, m-isopropenyldimethylbenzyl isocyanate (TMI), and 2 isocyanatoethyl methacrylate (IEM). The liquids were characterized by their refractive indices, infrared spectra, and percentage of isocynate groups in the molecule. Adhesive properties of these compounds were compared with those of oligomers prepared from methacrylate esters, IEM, and/or TMI which had been synthesized previously. Bond strengths of the sodium salt of ethylenediamine tetraacetic acid (Na2EDTA adjusted to pH 7.4) and glutaraldehyde-treated dentin cemented to composite resin with dilute solutions of the oligomers and then stored in water were determined by the procedure of Kemper and Kilian (1975). These adhesive compositions, especially formulations synthesized from vinyl monomers, adhered at least as well to dentin as did other dentin bonding agents. Oligomers synthesized with methacrylate esters bonded more strongly to bone than did other hard-tissue adhesives. These oligomeric compositions are also excellent soft-tissue adhesives. For example, they provide a strong bond between a collagenous substrate (such as calfskin) and cured denture-base resin. Provided that their biological properties prove satisfactory, these compositions could find many applications as hard- and soft-tissue adhesives in clinical dentistry. PMID- 2921394 TI - Relationships between the size, position, and angulation of human jaw muscles and unilateral first molar bite force. AB - Human subjects commonly show large variations in bite force produced at the first molar teeth. To evaluate the role of muscle cross-sectional sizes and lever arms in bite-force production, we correlated these variables in 11 healthy adults. Axial and coronal images obtained by magnetic resonance were combined with conventional lateral cephalograms and dental cast data to reconstruct the craniomandibular morphology in each subject. The cross-sectional sizes of the right masseter and medial pterygoid muscles, their lever arms, and the bite-point lever arms were measured directly from these reconstructions. Physiological recordings of bite force were made in the region of the right first molar by means of a customized transducer aligned perpendicular to the functional occlusal plane. The average bite force for the sample as a whole was 189 +/- 78 N. The coefficients of variance were greater for bite forces, and for the cross sectional sizes of the two muscles, than for their respective lever arms. Highly significant Pearson Product Moment correlation coefficients (p less than 0.005) were found between masseter and medial pterygoid cross-sectional size, and between the cross-sectional size of each muscle and bite force. No significant correlations (p greater than 0.1) were found between muscle or bite-point lever arms and bite force. Despite the fact that craniofacial spatial morphology may differ among subjects, jaw muscle size alone seems to explain most of the variation in bite force reported by ourselves and others. PMID- 2921393 TI - Comparison of fluoride uptake produced by tray and flossing methods in vitro. AB - The purposes of this study were to compare: (i) the fluoride (F) uptake by enamel in approximal areas of teeth when the F agent was applied in vitro via a tray or a flossing technique; and (ii) the effectiveness of two treatments--acidulated phosphate fluoride (APF) alone and CaHPO4.2H2O (DCPD)-forming pre-treatment followed by APF. Groups of three teeth (one premolar and two molars) were mounted in impression compounds simulating their oral configuration. In the tray group, teeth received one four-minute treatment by means of custom-formed trays. In the flossing group, the approximal areas of teeth were flossed for 40 sec twice daily for three days with an absorbent floss wetted with the treatment solution. All teeth were incubated in a saliva-like solution except during treatment. At the end of the three-day period, teeth were unmounted and washed in 1 mol/L KOH for 24 hours. The F uptake was calculated from biopsy data obtained before and after the treatment. The results showed that (i) DCPD-APF produced significantly greater F uptake than APF alone in both the tray and flossing methods, and (ii) the flossing technique produced significantly greater F uptake in the approximal areas than the tray method for either treatment. PMID- 2921395 TI - Model of mercury vapor transport from amalgam restorations in the oral cavity. AB - A model of the oral cavity was used as the basis for a discussion of the conditions prevalent during the transport of mercury vapor from amalgam restorations via the saliva to the gas phase of the oral cavity during respiration or during pumping of air through the mouth. It was found that the mercury diffusion rate through the saliva layer is independent of the air flow rate through the oral cavity. Mercury appears to be transported as atoms both in the aqueous phase of saliva and in the gas phase. The majority of the mercury atoms reaching the gas phase appears to originate directly from the surface of the amalgam restorations, passing through the saliva layer, while only a minority originates from mercury dissolved in the aqueous phase. The amount of mercury released per unit of time to the gas phase was shown to be independent of the air flow rate during respiration and pumping. Furthermore, the released mercury atoms are distributed partly to the gas phase, from which they are respired to the lungs and the environment, and partly to the saliva and the gastro-intestinal tract, by swallowing. PMID- 2921396 TI - A clinical, radiographic, and histological evaluation of permucosal dental implants of dense hydroxylapatite in dogs. AB - A clinical, histological, and radiographic examination was performed on 77 permucosal dental implants, made of dense sintered hydroxylapatite: 34 solid cylinders and 43 hollow cylinders. The hollow cylinders were pre-compressed between two titanium caps. The implants were placed in partly edentulous mandibles of dogs, and were physiologically loaded. Healing was clinically and radiographically evaluated during a six-month to five-year period. At various times, implants with their surrounding tissues were removed and prepared for light and electron microscopy. All implants showed a good initial fit and were maintained in place without undercut or mechanical stabilization. After 18 months, 76% of the solid cylinders had fractured at the implant/bone junction due to fatigue. However, the submerged portions of the solid cylinders were preserved without clinical problems, and became entirely embedded in bone. The pre-stressed implants did not fracture, and 91% were functioning 24 months after placement. The average scores of pocket depths and gingival bleeding showed no significant differences between implants and surrounding natural teeth. Bone deposition occurred on the entire surface of the implant below the crest of the alveolar bone, and intimate bone contact was confirmed by electron microscopy. It was also observed that a layer of bone tissue was deposited on the implant surface in the permucosal area just above the alveolar bone level. Embedding of gingival fibers in this layer resulted in gingival attachment to the implant, comparable with that of natural teeth. PMID- 2921397 TI - A look at the future of American dentistry. PMID- 2921398 TI - In favor of double testing. PMID- 2921399 TI - Punch technique--an alternative approach to the repair of pierced earlobe deformities. AB - The punch technique of repairing pierced earlobe deformities is a practical and simplified alternative to the usual method of repair. The procedure can easily be performed in any dermatology office since the instruments required are very basic. The technique is presented in a series of illustrations, and the results are cosmetically acceptable. PMID- 2921400 TI - Marking the spot. AB - Tattooing with India ink is a precise and practical method for identifying biopsy sites when there is a significant delay between biopsy and definitive surgery. PMID- 2921401 TI - Argon-pumped tunable dye laser therapy for facial port-wine stain hemangiomas in adults--a new technique using small spot size and minimal power. AB - A low power, argon-pumped tunable dye laser was used to deliver yellow light of 577 nm. Individual blood vessels within port-wine stain hemangiomas were treated with a 0.1-mm beam of light using 8 X magnification. This technique permits excellent resolution of facial and nuchal port-wine stain hemangiomas in adults without the adverse complications of textural change, permanent pigmentation abnormality, or hypertrophic scarring. PMID- 2921402 TI - Postirradiation extensive cicatricial scalp alopecia treated by tissue expansion. AB - The scalp of a 20-year-old woman with extensive cicatricial alopecia caused by x ray irradiation for tinea capitis has been reconstructed by the use of tissue expansion. Two stages were required to reconstruct the large defect. The hair bearing posterior scalp has been expanded to cover the whole irradiated area, creating a new anterior hairline and a pleasing cosmetic result. PMID- 2921403 TI - Topical hemostatic agents for dermatologic surgery. PMID- 2921404 TI - Acoustic distortion products in humans: systematic changes in amplitudes as a function of f2/f1 ratio. AB - The effects of primary-tone separation on the amplitude of distortion-product emissions (DPEs) at the 2f1-f2 frequency were systematically examined in ten ears of five subjects. All individuals had normal hearing and middle-ear function based upon standard clinical measures. Acoustic-distortion products were elicited at 1, 2.5, and 4 kHz by equilevel primaries at 65, 75, and 85 dB SPL, while f2/f1 ratios were varied in 0.02 increments from 1.01-1.41 (4 kHz), 1.01-1.59 (2.5 kHz), or 1.01-1.79 (1 kHz). A principal outcome reflected in the detailed structure of both average and individual ratio functions was a nonmonotonic change in DPE amplitude as the ratio of f2/f1 increased. Despite the presence of amplitude nonmonotonicities, there was clearly a region of f1 and f2 separation that generated a maximum DPE. The effects of primary-tone separation on DPE amplitudes were systematically related to DPE frequency and primary-tone level. For all three levels of stimulation, the f2/f1 ratio was inversely related to DPE frequency. Thus larger ratios reflecting a greater separation of f1 and f2 were more effective in generating DPEs at 1 kHz rather than at 4 kHz. The optimal ratio for 2.5 kHz fell at an intermediate value. Conversely, acoustic distortion product amplitude as a function of primary-tone level was directly related to the frequency separation of the primary tones. Regardless of the frequency region of the primary tones, smaller f2/f1 ratios were superior in generating DPEs in response to 65-dB stimuli, whereas larger ratios elicited bigger DPEs with primaries at 75 and 85 dB SPL. Within any specific stimulus-parameter combination, individual variability in DPE amplitude was noted. When all stimulus conditions describing the variations in frequency and level were considered, an f2/f1 ratio of 1.22 was most effective in maximizing DPE amplitude. PMID- 2921405 TI - Physiological responses to the pulsation threshold paradigm. I: Pulsation threshold patterns do not reproduce physiological rate profiles of high-pass and low-pass noise maskers. AB - This article compares psychophysical measures of human processing of acoustic stimuli with one neurophysiological representation (normalized discharge rate profiles) of those stimuli. Psychophysical pulsation threshold patterns (PTPs) were derived for high-pass and low-pass noise maskers. Spectral features of both maskers are clearly evident in the PTPs. However, while the representation of high-pass noise in the PTPs becomes sharper with increasing masker level, the representation of low-pass noise degenerates as masker level is increased. One assumption that has been used previously to interpret pulsation threshold data is that PTPs reflect the profile of activity in primary neural elements in response to the masking stimulus. To investigate this hypothesis, normalized-rate profiles of responses to both maskers were derived from populations of auditory-nerve fibers in cats. Normalized-rate profiles do not exhibit the same behavior as PTPs for high-pass noise maskers in that the neural representation of the band edge degenerates as sound level increases. Furthermore, the distinction between the passband and the stop band is lost in the neural rate profiles, whereas the distinction improves in the high-pass noise PTPs. PMID- 2921406 TI - Physiological responses to the pulsation threshold paradigm. II: Representations of high-pass noise in average rate measures of auditory-nerve fiber discharge. AB - In a companion article [L. I. Hellstrom, J. Acoust. Soc. Am. 85, 230-242 (1989)], it was shown that psychophysical pulsation threshold masking patterns (PTPs) for high-pass noise maskers are not a simple transformation of the profile of activity evoked in the auditory nerve by the masker. In this article, PTPs are compared with neural representations in which interactions of masker and probe are considered. It is hypothesized that, at pulsation threshold, some criterion value of rate change occurs when the stimulus switches from masker to probe. The iso-rate probe level, defined for single auditory-nerve fibers, is the probe level at which this rate change is zero. Iso-rate probe levels are lowest when probe frequency equals best frequency (BF) of the fiber. Profiles of iso-rate probe level versus BF (equal to probe frequency) are qualitatively similar to PTPs but differ quantitatively, e.g., in the rate of growth of probe level with masker level (1.2 dB/dB for PTPs, 0.54 dB/dB for iso-rate profiles). Quantitative differences can be further reduced by requiring a positive rate criterion. These results suggest that PTPs are not solely a reflection of the internal representation of the masker, but reflect responses to the probe tone as well. PMID- 2921407 TI - Spectral differences in the ability of temporal gaps to reset the mechanisms underlying overshoot. AB - When very brief tonal signals are presented immediately after the onset of a gated noise masker, detectability can be 10-20 dB worse than when the signal is delayed by several hundred milliseconds, an effect known as the overshoot. It has long been known that, when an "onset" is created in an otherwise continuous, broadband masker by briefly turning it off and on again, the detectability of a brief signal presented soon after this temporal gap will decline gradually as the gap is increased from a few milliseconds to a few hundred milliseconds. In other words, the auditory system recovers to its quiescent, resting state following an adequate silent interval. Here, the broadband maskers consisted of three adjacent spectral bands--one centered on the frequency of the tonal signal, one low passed below the lower edge of the center band, and one high passed above the upper edge of the center band. The signal was a 2500-Hz tone having a total duration of 6 ms. In different blocks of trials, either all three bands, only the center band, or only the two flanking bands were temporally gapped by a duration ranging from 10-300 ms. When the center band was about 750 Hz wide (about 2.5 critical bandwidths), this differential gapping process resulted in typical recovery functions when all three bands (the entire spectrum) or when just the two flanking bands were gapped. However, when only the center band was gapped, there was no evident recovery--rather, detectability remained near the signal level required with a continuous masker, even for a gap duration of 300 ms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2921408 TI - Comodulation masking release for various monaural and binaural combinations of the signal, on-frequency, and flanking bands. AB - The threshold for a signal masked by a narrow band of noise centered at the signal frequency (the on-frequency band) may be reduced by adding to the masker a second band of noise (the flanking band) whose envelope is correlated with that of the first band. This effect is called comodulation masking release (CMR). These experiments examine two questions. (1) How does the CMR vary with the number and ear of presentation of the flanking band(s)? (2) Is it possible to obtain a CMR when a binaural masking level difference (BMLD) is already present, and vice versa? Thresholds were measured for a 400-ms signal in a continuous 25 Hz-wide noise centered at signal frequencies (fs) of 250, 1000, and 4000 Hz. This masker was presented either alone or with one or more continuous flanking bands whose envelopes were either correlated or uncorrelated with that of the on frequency band; their frequencies ranged from 0.5fs to 1.5fs. CMRs were measured for six conditions in which the signal, the on-frequency band, and the flanking band(s) were presented in various monaural and binaural combinations. When a single flanking band was used, the CMR was typically around 2-3 dB. The CMR increased to 5-6 dB if an additional flanking band was added. The effect of the additional band was similar whether it was in the same ear as the original band or in the opposite ear. At the lowest signal frequency, a large CMR was observed in addition to a BMLD and vice versa. At the highest signal frequency, the extra release from masking was small. The results are interpreted in terms of the cues producing the CMR and the BMLD. PMID- 2921409 TI - Comodulation masking release (CMR) as a function of masker bandwidth, modulator bandwidth, and signal duration. AB - These experiments examine how comodulation masking release (CMR) varies with masker bandwidth, modulator bandwidth, and signal duration. In experiment 1, thresholds were measured for a 400-ms, 2000-Hz signal masked by continuous noise varying in bandwidth from 50-3200 Hz in 1-oct steps. In one condition, using random noise maskers, thresholds increased with increasing bandwidth up to 400 Hz and then remained approximately constant. In another set of conditions, the masker was multiplied (amplitude modulated) by a low-pass noise (bandwidth varied from 12.5-400 Hz in 1-oct steps). This produced correlated envelope fluctuations across frequency. Thresholds were generally lower than for random noise maskers with the same bandwidth. For maskers less than one critical band wide, the release from masking was largest (about 5 dB) for maskers with low rates of modulation (12.5-Hz-wide low-pass modulator). It is argued that this release from masking is not a "true" CMR but results from a within-channel cue. For broadband maskers (greater than 400 Hz), the release from masking increased with increasing masker bandwidth and decreasing modulator bandwidth, reaching an asymptote of 12 dB for a masker bandwidth of 800 Hz and a modulator bandwidth of 50 Hz. Most of this release from masking can be attributed to a CMR. In experiment 2, the modulator bandwidth was fixed at 12.5 Hz and the signal duration was varied. For masker bandwidths greater than 400 Hz, the CMR decreased from 12 to 5 dB as the signal duration was decreased from 400 to 25 ms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2921410 TI - Minimum audible angle thresholds obtained under conditions in which the precedence effect is assumed to operate. AB - Two experiments were conducted to examine the ability of human listeners to localize the "lag" or "echo" source in a precedence effect paradigm. A 5-ms noise burst was presented from a source located between 554-279 cm from the subject. This "lead" source was always located at 0 degrees azimuth. At the same time, one of two sources located at a distance of 610 cm from the subject was also activated with the same 5-ms noise burst. The subject's task was to identify which lag source had been active. Across sessions, the angular distance between the lag sources was varied, so as to allow a determination of the minimum audible angle (MAA) that could be resolved. Tests were run in a room designed to minimize reflections and in a hallway that was acoustically quite complex. No systematic differences in MAA thresholds were observed as a function of the environment employed. MAA thresholds obtained without the signal from the lead speaker were less than 1 degree for four of the five subjects tested. The precedence effect, as measured by the change in the MAA threshold, appears to have only a modest influence on localization performance. Under conditions in which the lead source was concurrently active, the thresholds were generally elevated by only 2 degrees 4 degrees. A reduction of this magnitude in the ability to resolve the position of the lag source does not seem to be sufficient, in itself, to account for the excellent localization performance frequently observed in reflective environments. PMID- 2921411 TI - Kanamycin induced low-frequency hearing loss in the budgerigar (Melopsittacus undulatus). AB - The chronic effects of kanamycin (KM) on hearing in the budgerigar were investigated by behavioral audiometry. The birds received a daily intramuscular injection of KM (100 mg/kg or 200 mg/kg) for 10 successive days, and absolute thresholds between pre- and post-treatment were compared. KM induced both transient and permanent low-frequency specific hearing loss; i.e., the elevation of threshold for frequencies below 1 kHz was greater than that for frequencies above 1 kHz. Moreover, the degree of hearing loss was dose dependent. The low frequency selective effects of KM in the present study were contrary to the high frequency specificity of aminoglycoside ototoxicity in mammals. To assess the effect of KM on auditory frequency resolution, critical ratios were estimated in pathological birds with low-frequency specific hearing loss. There was a linear relation between shift in critical ratio and shift in absolute threshold, suggesting that the increase in the critical ratio is due to a decrease in the efficiency of the detector mechanism rather than a change in the spectral resolving power of the birds. PMID- 2921412 TI - Articulatory dynamics of loud and normal speech. AB - A comparison was made between normal and loud productions of bilabial stops and stressed vowels. Simultaneous recordings of lip and jaw movement and the accompanying audio signal were made for four native speakers of Swedish. The stimuli consisted of 12 Swedish vowels appearing in an /i'b_b/ frame and were produced with both normal and increased vocal effort. The displacement, velocity, and relative timing associated with the individual articulators as well as their coarticulatory interactions were studied together with changes in acoustic segmental duration. It is shown that the production of loud as compared with normal speech is characterized by amplification of normal movement patterns that are predictable for the above articulatory parameters. In addition, it was observed that the acoustic durations of bilabial stops were shortened, whereas stressed vowels were lengthened during loud speech production. Two interpretations of the data are offered, viewing loud articulatory behavior as a response to production demands and perceptual constraints, respectively. PMID- 2921413 TI - The influence of final-syllable position on the vowel and word duration of deaf talkers. AB - Hearing talkers produce shorter vowel and word durations in multisyllabic contexts than in monosyllabic contexts. This investigation determined whether a similar effect occurs for deaf talkers, a population often characterized as lacking coarticulation in their speech. Four prelingually deafened adults and two hearing controls produced three sets of word sequences. Each set included a kernel word and six derived forms (e.g., "speed," "speedy," "speeding," etc.). The derived forms were created by adding unstressed and stressed syllables to the kernel form. A spectrographic analysis indicated that the deaf subjects did not always decrease word and vowel durations for the derivatives. Unlike hearing speakers, they often did not reduce vowel segments more than consonant segments. Three explanations are forwarded for the shortening effects. One relates to the implementation of temporal rules, the second concerns the organization imposed upon the articulators to produce speech, and the third suggests a language independent vocal tract characteristic. The role of auditory information in developing the shortening effects is also considered. PMID- 2921414 TI - Predictors of subsyllabic durations in speech motor control. AB - Speech motor control timing was examined by means of a multiple correlational analysis involving interarticulatory delay and speech rate as predictor variables, and four subsyllabic time segments of the syllable [ka] as dependent variables. The hypothesis was that the two putative temporal constraints have differential predictive capacity for various segments of the syllable. Results from 11 subjects were in support of the hypothesis. Syllable onset duration was reliably predicted by the linear addition of interarticulatory delay and speech rate, while the duration of the midportion of the syllable was nearly exclusively predicted by the overall speech rate. This model was found to be applicable to all conditions of normal and clenched teeth, context-free and contextual, normally paced and rapid speech production, with minor differences in predictive capacity for different conditions. PMID- 2921415 TI - Modeling the perception of concurrent vowels: vowels with the same fundamental frequency. AB - The ability of listeners to identify pairs of simultaneous synthetic vowels has been investigated in the first of a series of studies on the extraction of phonetic information from multiple-talker waveforms. Both members of the vowel pair had the same onset and offset times and a constant fundamental frequency of 100 Hz. Listeners identified both vowels with an accuracy significantly greater than chance. The pattern of correct responses and confusions was similar for vowels generated by (a) cascade formant synthesis and (b) additive harmonic synthesis that replaced each of the lowest three formants with a single pair of harmonics of equal amplitude. In order to choose an appropriate model for describing listeners' performance, four pattern-matching procedures were evaluated. Each predicted the probability that (i) any individual vowel would be selected as one of the two responses, and (ii) any pair of vowels would be selected. These probabilities were estimated from measures of the similarities of the auditory excitation patterns of the double vowels to those of single-vowel reference patterns. Up to 88% of the variance in individual responses and up to 67% of the variance in pairwise responses could be accounted for by procedures that highlighted spectral peaks and shoulders in the excitation pattern. Procedures that assigned uniform weight to all regions of the excitation pattern gave poorer predictions. These findings support the hypothesis that the auditory system pays particular attention to the frequencies of spectral peaks, and possibly also of shoulders, when identifying vowels. One virtue of this strategy is that the spectral peaks and shoulders can indicate the frequencies of formants when other aspects of spectral shape are obscured by competing sounds. PMID- 2921416 TI - Interactive factors in consonant confusion patterns. AB - Confusion patterns among English consonants were examined using log-linear modeling techniques to assess the influence of low-pass filtering, shaped noise, presentation level, and consonant position. Ten normal-hearing listeners were presented consonant-vowel (CV) and vowel-consonant (VC) syllables containing the vowel /a/. Stimuli were presented in quiet and in noise, and were either filtered or broadband. The noise was shaped such that the effective signal level in each 1/3 octave band was equivalent in quiet and noise listening conditions. Three presentation levels were analyzed corresponding to the overall rms level of the combined speech stimuli. Error patterns were affected significantly by presentation level, filtering, and consonant position as a complex interaction. The effect of filtering was dependent on presentation level and consonant position. The effects stemming from the noise were less pronounced. Specific confusions responsible for these effects were isolated, and an acoustical interaction is suggested, stressing the spectral characteristics of the signals and their modification by presentation level and filtering. PMID- 2921417 TI - Stop-consonant recognition for normal-hearing listeners and listeners with high frequency hearing loss. I: The contribution of selected frequency regions. AB - The purpose of this study is to specify the contribution of certain frequency regions to consonant place perception for normal-hearing listeners and listeners with high-frequency hearing loss, and to characterize the differences in stop consonant place perception among these listeners. Stop-consonant recognition and error patterns were examined at various speech-presentation levels and under conditions of low- and high-pass filtering. Subjects included 18 normal-hearing listeners and a homogeneous group of 10 young, hearing-impaired individuals with high-frequency sensorineural hearing loss. Differential filtering effects on consonant place perception were consistent with the spectral composition of acoustic cues. Differences in consonant recognition and error patterns between normal-hearing and hearing-impaired listeners were observed when the stimulus bandwidth included regions of threshold elevation for the hearing-impaired listeners. Thus place-perception differences among listeners are, for the most part, associated with stimulus bandwidths corresponding to regions of hearing loss. PMID- 2921418 TI - Stop-consonant recognition for normal-hearing listeners and listeners with high frequency hearing loss. II: Articulation index predictions. AB - Articulation index (AI) theory was used to evaluate stop-consonant recognition of normal-hearing listeners and listeners with high-frequency hearing loss. From results reported in a companion article [Dubno et al., J. Acoust. Soc. Am. 85, 347-354 (1989)], a transfer function relating the AI to stop-consonant recognition was established, and a frequency importance function was determined for the nine stop-consonant-vowel syllables used as test stimuli. The calculations included the rms and peak levels of the speech that had been measured in 1/3 octave bands; the internal noise was estimated from the thresholds for each subject. The AI model was then used to predict performance for the hearing-impaired listeners. A majority of the AI predictions for the hearing-impaired subjects fell within +/- 2 standard deviations of the normal hearing listeners' results. However, as observed in previous data, the AI tended to overestimate performance of the hearing-impaired listeners. The accuracy of the predictions decreased with the magnitude of high-frequency hearing loss. Thus, with the exception of performance for listeners with severe high-frequency hearing loss, the results suggest that poorer speech recognition among hearing impaired listeners results from reduced audibility within critical spectral regions of the speech stimuli. PMID- 2921419 TI - Some effects of talker variability on spoken word recognition. AB - The perceptual consequences of trial-to-trial changes in the voice of the talker on spoken word recognition were examined. The results from a series of experiments using perceptual identification and naming tasks demonstrated that perceptual performance decreases when the voice of the talker changes from trial to trial compared to performance when the voice on each trial remains the same. In addition, the effects of talker variability on word recognition appeared to be more robust and less dependent on task than the effects of word frequency and lexical structure. Possible hypotheses regarding the nature of the processes giving rise to these effects are discussed, with particular attention to the idea that the processing of information about the talker's voice is intimately related to early perceptual processes that extract acoustic-phonetic information from the speech signal. PMID- 2921420 TI - Acoustic properties and perception of stop consonant release transients. AB - This study focuses on the initial component of the stop consonant release burst, the release transient. In theory, the transient, because of its impulselike source, should contain much information about the vocal tract configuration at release, but it is usually weak in intensity and difficult to isolate from the accompanying frication in natural speech. For this investigation, a human talker produced isolated release transients of /b,d,g/ in nine vocalic contexts by whispering these syllables very quietly. He also produced the corresponding CV syllables with regular phonation for comparison. Spectral analyses showed the isolated transients to have a clearly defined formant structure, which was not seen in natural release bursts, whose spectra were dominated by the frication noise. The formant frequencies varied systematically with both consonant place of articulation and vocalic context. Perceptual experiments showed that listeners can identify both consonants and vowels from isolated transients, though not very accurately. Knowing one of the two segments in advance did not help, but when the transients were followed by a compatible synthetic, steady-state vowel, consonant identification improved somewhat. On the whole, isolated transients, despite their clear formant structure, provided only partial information for consonant identification, but no less so, it seems, than excerpted natural release bursts. The information conveyed by artificially isolated transients and by natural (frication-dominated) release bursts appears to be perceptually equivalent. PMID- 2921421 TI - The elastic microstructure of various tissues. AB - Previous work has indicated that a modified Quate-Lemons scanning acoustic microscope (SAM) is capable of measuring the acoustic propagation properties of sections of biological tissue. The lens is excited by an impulse, rather than a tone burst, and the undemodulated returning signal from the tissue is recorded. The variations in received signal with time are used to deduce the sound speed, attenuation, impedance, and section thickness. In this article, the technique is applied to various types of tissue, and the variations in acoustic propagation properties are computed. Conventional tone burst SAM images at 425 MHz are compared with the time resolved data in order to elucidate the contrast mechanisms. The effects of varying the frequency and position of the focal plane on the tone burst images are interpreted in the light of the broadband results. PMID- 2921422 TI - Simulating the open-loop transfer function as a means for understanding acoustic feedback in hearing aids. AB - Suppressing unstable acoustic feedback in hearing aids will first require knowledge of the open-loop transfer functions of such systems. Reported herein is a mathematical technique for simulating the open-loop transfer function of an in situ eyeglass-type hearing aid. In particular, a computer program was developed that characterized the hearing aid as a serial connection of two-port blocks, each representing one individual component of a hearing aid. Included, for example, were two-port blocks representing the microphone, amplifier, receiver, sound tubes leading to the eardrum (including the ear canal itself), earmold vent, and external pathway from the vent outlet back to the microphone. The computer program was validated by replicating laboratory data derived from an experiment involving a nonstandard manikin fitted with a nonstandard artificial ear. Next, the open-loop transfer function of an eyeglass-type hearing aid in situ on the manikin was simulated via the computer program. Unfortunately, those computer-generated data were not replicated in the laboratory due to the difficulty encountered in actually measuring the open-loop transfer function. Nevertheless, investigators were able to utilize those data to predict, within +/ 25 Hz, the "squeal" frequency of unstable acoustic feedback. PMID- 2921423 TI - Intensity discrimination of pulsed tones by the goldfish (Carassius auratus). AB - Intensity discrimination thresholds for 500-ms pure-tone bursts were measured as a function of frequency in the goldfish (Carassius auratus) using classical respiratory conditioning. At 55-dB sensation level (SL), thresholds range from 1.44-2.2 dB between 100 and 1600 Hz. There is not important effect of frequency on intensity discrimination. Thresholds at 35-dB SL average 0.7 dB higher than at 55-dB SL. This is a small difference in the context of the threshold variability. In intensity discrimination acuity, the goldfish is quantitatively similar to other vertebrates, including birds and mammals. PMID- 2921424 TI - Frequency discrimination in the goldfish (Carassius auratus): effects of roving intensity, sensation level, and the direction of frequency change. AB - The ability of goldfish to detect a change in the frequency of 400-Hz pure-tone bursts was studied using classical respiratory conditioning. The frequency discrimination threshold was measured at 15-, 35-, and 55-dB sensation level (SL), under conditions of (1) constant intensity, (2) roving intensity (plus and minus 6-dB burst-to-burst variation in intensity), (3) upward frequency change, and (4) downward frequency change. There was no overall effect of SL on frequency discrimination, but roving the intensity elevated thresholds by about 6 Hz (33%) and increased variability. Upward shifts in frequency elevated thresholds slightly (by 2 Hz or 10%) relative to downward shifts. These relatively small and statistically insignificant effects suggest that earlier measures of frequency discrimination in the goldfish are not due to the detection of simple changes in spike rate within individual peripheral channels. PMID- 2921425 TI - American Cancer Society and smoking cessation. PMID- 2921426 TI - Laboratory guidelines and infection control. PMID- 2921427 TI - Tobacco use and oral health. PMID- 2921428 TI - The optimum placement-site of the electrode in electric pulp testing of the 12 anterior teeth. AB - The present study of 2,387 recordings of 12 anterior teeth in 53 patients indicates that the incisal edge is the optimal placement-site for the electric pulp tester to determine the lowest response threshold. The results show significant individual variations in the lowest threshold responses of the cervical-third, middle-third, incisal one-third, and incisal edge sites on a tooth, with a confidence level of 99%, according to the analysis of variance. The maxillary teeth gave a higher response threshold than the mandibular teeth and different types of teeth (canines and incisors) had statistically significant different response thresholds. The application of the electric pulp tester to the incisal-edge region with exposed dentin produced the most significant decrease in the threshold response. PMID- 2921429 TI - Rapidly progressive periodontal disease associated with HIV infection: report of case. AB - A case of rapidly progressive periodontal disease associated with human immunodeficiency virus (HIV) infection is presented. Rapid horizontal bone loss, with only moderate inflammation, occurred during a 13-month period. Pocket depth was significantly less than anticipated, given the degree of bone loss. The patient had no signs or symptoms of acquired immune deficiency syndrome (AIDS). The cause, features, diagnosis, and management are discussed. PMID- 2921430 TI - Cheilitis glandularis: a pediatric case report. AB - Cheilitis glandularis is a rare disorder, usually affecting the lower lip of adults. This case involved both lips of an adolescent male. A familial history of the condition may have contributed to the involvement of both lips, and may reinforce the importance of hereditary tendency in the development of cheilitis glandularis. Emotional disturbance and poor oral hygiene also had a role in the disorder in this case, which was successfully treated with surgery. PMID- 2921431 TI - Prevalence of perforations in disposable latex gloves during routine dental treatment. AB - Durability of gloves with respect to reducing cross-contamination and decreasing the risk of occupationally acquired infections was studied. In this study, pinholes were found in 1.8% of unused surgical latex gloves and 2.0% of latex examination gloves. The incidence of pinhole defects in gloves emphasizes the importance of operative techniques that minimize stress to the glove and the need to change gloves, especially for procedures lasting more than 2 hours. PMID- 2921432 TI - Effect of finishing on the in vivo wear rate of a posterior composite resin. AB - A problem with posterior composites is an unacceptable wear level. One factor contributing to inadequate wear resistance may be the way the restoration is surfaced or finished. A clinical study was carried out to determine the influence of finishing on the wear rate of a posterior composite resin. Except for the first 30 days, the resistance to wear was significantly higher for the unfinished group as compared to those that received a conventional finish. The average difference in wear between the two groups was nearly 40 microns. PMID- 2921433 TI - Advertising, ethics, and the free market. PMID- 2921434 TI - Code on dental procedures and nomenclature. Council on Dental Care Programs. PMID- 2921435 TI - Revised ANSI/ADA specification no. 5 for dental casting alloys. Council on Dental Materials, Instruments, and Equipment. PMID- 2921436 TI - Call to action on the global poverty reduction act. PMID- 2921437 TI - FYI: more news about Olestra. PMID- 2921438 TI - O-Anon, resource for significant others of bulimic patients. PMID- 2921439 TI - Modified food starch and nutrient density of baby foods. PMID- 2921440 TI - Implementing food policy: Calorie Conscious Consumer Project. PMID- 2921441 TI - Evaluation of a hospital-based education program for patients with diabetes. AB - Ninety-three hospitalized patients with diabetes were followed for a 4-month period after discharge. Fifty-three of them attended an inpatient diabetes education program. The primary objectives of this research were to (a) determine the effectiveness of the program in improving diabetes-related behaviors and outcomes of the patients attending the program and (b) study the effects of time on those behaviors and outcomes. Examples of self-care behaviors included eating three meals per day, daily urine testing, and maintaining an exercise program. Outcome measures included reduced fasting blood glucose levels, reduced insulin requirements, fewer hospitalizations, and fewer emergency room visits. At 1 and 4 months after discharge, the group that attended the program reported better compliance for all self-care behaviors than did the group that did not attend the program. Outcomes were also better for the group that attended the education program. PMID- 2921442 TI - Teaching self-management skills to cystic fibrosis patients and its effect on their caloric intake. AB - This study was undertaken to examine whether cystic fibrosis patients who received nutrition counseling based on self-management skills had an increased caloric intake and enhanced body mass index (kg/m2) values. Thirty-seven patients, aged 4 to 29 years, were placed on a nonrestricted nutrition program for a study period of 4 years. Bandura's self-management principles were applied in counseling patients to meet their nutrition needs. The results showed significant increases in energy intake and body mass index values (p less than .001). The mean energy intake increased from 93.6 +/- 16.9% of the Recommended Dietary Allowance to 125.8 +/- 24.1% of the RDA, and mean body mass index value increased from 16.9 +/- 2.3 to 18.8 +/- 2.5. Pulmonary functions remained unchanged during the counseling period. Four to six counseling sessions were required before the mean caloric intake of the patients increased to the desired goal of 115% of the RDA. During the remainder of the study period, the mean caloric intake rose to 125% of the RDA. The results of this study suggest that cystic fibrosis patients are able to increase their caloric intake significantly with counseling. PMID- 2921443 TI - Management activities in community dietetics practice. AB - Information on the management activities of community dietitians was obtained through a mail survey of 350 randomly selected community dietitians. Subjects provided information on their management level, the importance to their job performance of 83 management activity statements, and the percent of time they spent performing management activities in each of nine categories. Twenty-nine percent of the respondents indicated job responsibilities in lower-level management; 45% had mid-level and 26% had upper-level management responsibilities. Numbers of activities rated essential or very important increased as management levels increased. Kinds of activities changed from technical to human to conceptual as management levels increased. Mid-level management subjects, while still spending time working with clients, reported spending considerable time on coordinating, investigating, and evaluating, often reporting as much time spent on those activities as did upper-level management subjects. Definitions provided by respondents indicated great diversity in job requirements and settings. PMID- 2921444 TI - Dietary habits, weight history, and vitamin supplement use in elderly osteoarthritis patients. AB - Osteoarthritis is a chronic disabling disease in the elderly, but few studies have examined nutritional parameters of osteoarthritis patients. For 82 ambulatory elderly osteoarthritis patients, a registered dietitian assessed the following: consumption of 72 food items, using a food-frequency questionnaire; weight history, by measuring current weight and asking the weight at age 20, maximum adult weight, and minimum adult weight; dietary habits; and vitamin supplement consumption. Joint pain and activities of daily living (ADL) were assessed by a physician. On the basis of the Four Food Group guidelines, dietary intakes were suboptimal in the dairy and grain groups, which are important sources of calcium, vitamin D, thiamin, iron, and riboflavin. Eighty percent of the sample were obese (BMI greater than or equal to 27). The average weight change since early adulthood was a gain of 59 lb. Current joint pain and ADL restrictions were not related to obesity or weight gain. Vitamin/mineral supplements were consumed by 37% of the sample. PMID- 2921445 TI - Vitamin and mineral supplementation practices of adults in seven western states. AB - Seven western states (Arizona, California, Idaho, Nevada, New Mexico, Oregon, and Wyoming) were surveyed in 1986 to determine the extent of vitamin/mineral supplementation and dosage levels of single supplements. Questionnaires were mailed to 3,500 individuals. A 57.8% response rate was obtained from the deliverable surveys, with a sample size of 1,730. The sample consisted of 54% women and 46% men and was predominantly white (88.9%). Fifty-four percent of the sample consumed some type of supplement; multiple vitamin/minerals were consumed with the greatest frequency. For single supplements, vitamin C was reported with the greatest frequency (23.1%), followed by some type of calcium supplement (22.5%) and vitamin E (11.1%). More than 80% of the vitamin C users indicated a dosage of 250 mg/day. Most respondents consumed calcium dosages of less than 1,000 mg/day. For vitamin E, 75% of the users consumed more than 200 IU/day. The data suggest that the potential for toxicity due to excess supplementation levels exists in the western states studied. PMID- 2921446 TI - Nutrient intake in young, highly competitive gymnasts. PMID- 2921447 TI - Evaluation of the nutrition counseling environment of hospitalized patients. PMID- 2921448 TI - Comparison of conventional and videotaped diabetic exchange lists instruction. PMID- 2921449 TI - Energy and nutrient intakes of soldiers consuming MRE operational rations: physiological correlates. PMID- 2921450 TI - Estimation of product yield and numbers of portions of turkey rolls in a convection oven. PMID- 2921451 TI - Familial aggregation of multiple myeloma and central nervous system diseases. AB - Degenerative central nervous system diseases such as Alzheimer's disease and lymphoreticular malignancies such as multiple myeloma occur with increased frequency with advancing age. Relatives of early-onset Alzheimer's disease patients may have an increased risk of lymphoreticular malignancies. This led us to evaluate the family history of central nervous system diseases in a case control study of multiple myeloma. Thirteen of 439 multiple myeloma cases had one or more first-degree relatives with degenerative or demyelinating central nervous system disease. In comparison, there were nine "positive" family histories in 1,317 matched hospital controls (relative risk = 4.4, 95% confidence interval = 1.9-10.3). Relative risks for the component categories of Parkinson's disease, multiple sclerosis, and miscellaneous degenerative central nervous system diseases were 3.0, 4.0 and 11.9, respectively. Our findings suggest that the degenerative and demyelinating central nervous system diseases and the lymphoreticular malignancies may comprise an etiologically related group of "protean diseases." These diseases may have a shared genetic susceptibility, possibly an immunologic abnormality. The varied disease manifestation in family members suggests a second necessary etiologic step of a variable and possibly environmental nature. PMID- 2921452 TI - Characteristics, diagnosis, and treatment of alcoholism in elderly patients. AB - The purpose of this study is to examine the ability of physicians to diagnose alcoholism in the elderly patient and to define characteristics specific to the elderly patient with alcoholism. During a 3-month period, all new admissions to the medical service of The Johns Hopkins Hospital were screened for alcoholism with two screening tests (the CAGE questionnaire and Short Michigan Alcohol Screening Test). The prevalence of screen-positive alcoholism was 27% in patients under 60 years of age and 21% in patients 60 years and older. Elderly patients with alcoholism were more likely to be black (P less than .01), but did not differ significantly in any other way from elderly patients who did not have alcoholism. Although 60% of screen-positive young patients with alcoholism were identified by their houseofficers, only 37% of elderly patients with screen positive alcoholism were so identified (P less than .05). The elderly patients with alcoholism were significantly less likely to be diagnosed by their houseofficer if they were white, female, or had completed high school (P less than .01). Even when diagnosed, elderly patients with alcoholism were less likely than younger patients with alcoholism to have treatment recommended by their houseofficers (P less than .05) and, if treatment were recommended, it was less likely to be initiated (P less than .05). These data suggest that current medical education is deficient in providing physicians with the skills to detect and treat elderly patients with alcoholism. PMID- 2921453 TI - Drug-induced illness as a cause for admission to a community hospital. AB - To assess the rate of occurrence of drug-induced illness as a cause for admission to the general medicine service of a community hospital, charts were reviewed retrospectively of all patients admitted to the service over two randomly selected one-month periods. Statistical analysis was performed on patients over and under the age of 65, and on iatrogenic and noniatrogenic admissions. Twenty three of 244 patients (9.4%) were admitted with drug-induced illness. Patients with drug-induced illness had 5.7 medications as compared to 3.2 medications per patient admitted for other reasons (P less than .05). A single drug was responsible for 61% of all drug-induced illness admissions. Aspirin and other nonsteroidal anti-inflammatory agents were most often implicated. Eighteen of 155 elderly patients (11.7%) were admitted with drug-induced illness. These patients were on an average of 6.3 medications as compared with 3.8 medications per elderly patient admitted for other causes (P less than .005). Polypharmacy and a preponderantly elderly population may explain the substantial number of admissions caused by adverse drug reactions. Further research to assess the role of patient age and the number and type of medications involved in the event of drug-induced illness requires standardization of definition and diagnostic criteria. PMID- 2921454 TI - Prescribing of psychotropics in elderly nursing home patients. AB - This study examined the prescribing of psychotropic drugs for patients 65 years of age and older in nursing homes using data from the 1984 National Nursing Home Survey pretest. The most frequently used antipsychotic, anxiolytic, antidepressant, and sedative/hypnotic medications were respectively: haloperidol, hydroxyzine, doxepin, and temazepam. Results indicate that more than one-fifth of the patients having orders for psychotropic medications did not have a documented mental disorder. More than one-fourth of the study patients had orders for more than one psychotropic medication. Nursing home patients who received psychotropics had concurrent orders for an average of 3.3 nonpsychotropic medications, many of which could increase the possibility of drug interactions and potential side effects. PMID- 2921455 TI - Deaths from residential fires among older people, United States, 1984. AB - Deaths from fires are the fifth leading cause of injury death among people aged 65 years or older. To describe the epidemiology of deaths from residential fires among older people, we analyzed mortality data for 1984 collected by the National Center for Health Statistics. Although older people represented only 12% of the U.S. population in 1984, they accounted for 29% (1,278) of that year's 4,466 residential fire deaths. Conflagrations accounted for 78% of older people's deaths from residential fires; clothing ignitions and other fires accounted for 11% each. Residential fire death rates increased with advancing age. Older black people had death rates 4.6 times the death rates of older white people. Older males had higher death rates than older females. Host, environmental, and behavioral risk factors for residential fire deaths among older people and potential strategies for intervention are discussed. Unless intervention strategies are focused on older people, the residential fire death toll in the U.S. may actually grow as the population of older people increases from 12% of the population in 1984 to about 21% of the population in 2030. PMID- 2921456 TI - Methods used to manage urinary incontinence by older adults in the community. AB - This paper addresses the ways that noninstitutionalized older adults deal with involuntary urine loss. The data come from a 1983-1984 sample survey of Washtenaw County, Michigan residents aged 60 and over. Five hundred twelve self-reported incontinent respondents are included in the analyses. About a quarter of the incontinent respondents had discussed their condition with a doctor in the previous year, while 66% used one or more methods to control urine loss. Respondents preferred using absorbent products (47% of those who used some method) and locating a toilet upon reaching a destination (42%). Fewer respondents manipulated their voiding patterns (29%) or diet and fluid intake (17%), or did pelvic muscle exercises (10%). Only 7% were taking medication for their incontinence. Logistic regression analyses were performed to identify factors associated with the choice of actions. Predictors were taken from theoretical models of health service utilization and health behavior, and included predisposing characteristics, health beliefs, enabling factors, and illness variables. Illness variables, particularly severity and type of incontinence, were the best predictors of consultation with a doctor and use of any urine control method. The predictors were less useful for understanding the choice of a specific method. PMID- 2921457 TI - Evaluation of a supervised exercise program in a geriatric population. AB - Most studies that assess the effects of exercise in the elderly involve subjects who are in good health. The objective of this prospective longitudinal study was to examine the impact of exercise on cardiovascular fitness, flexibility, and strength in an elderly population that included chronically ill individuals. Patients were recruited initially from a population of veterans over 64 years of age who use a VA outpatient clinic as their regular source of care. The exercise intervention consisted of 90 minutes of exercise 3 days per week at 70% of the patient's maximal capacity. Activities included stationary cycling, stretching, weight training, and walking. Of 69 patients who began the program, 49 (71%) reached 4-month follow-up. Most patients completing follow-up (76%) had at least one chronic disease, such as arthritis, hypertension, or heart disease. Patients who dropped out were more likely to have multiple chronic illnesses than those who remained in the program. Average weekly attendance was 65% and was stable over time. Improvements in cardiovascular fitness at 4-month follow-up were significant: Metabolic equivalents increased from 7.1 +/- 2.3 to 8.3 +/- 2.6 (P less than .001), treadmill time increased from 8.5 +/- 3.8 to 11.2 +/- 4.2 minutes (P less than .001), submaximal heart rate decreased from 123.7 +/- 18.8 to 118.8 +/- 19.4 beats per minute (P less than .001) and resting heart rate decreased from 68.1 +/- 10.6 to 63.3 +/- 11.6 beats per minute (P = .005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2921459 TI - Reasons for nonimmunization against influenza in the aged. PMID- 2921458 TI - Acute mesenteric infarction in elderly patients. AB - The clinical features, the treatment given, the factors governing treatment selection, and the result of such treatment were analyzed in all patients aged 65 years and over in whom a tissue diagnosis of acute mesenteric infarction was made at a major teaching hospital. Thirty-two such patients, of mean age 78.5 years, were identified during the 8-year study period. Expected clinical features of bowel infarction were commonly absent; for example, there was no abdominal pain and no abdominal tenderness in 29% and 26% of patients, respectively. A sizeable minority of patients (29%) were acutely confused at presentation. All patients not undergoing surgery died shortly after admission to hospital. For those 20 patients (63%) who underwent abdominal surgery, half were discharged alive from hospital. Whether or not the patient survived was associated with the ward to which they were originally admitted. Those admitted to a surgical ward tended to be younger and had a more typical clinical presentation than their counterparts admitted to a medical ward. In particular they were more likely to have abdominal pain and distention and less likely to be confused. Surgical intervention was undertaken more often and earlier in those admitted to surgical wards and this may have accounted for the better outcome. It should be emphasized that acute mesenteric ischemia is a potentially correctable surgical condition even in very elderly people. A realization that the presentation is often atypical should increase the likelihood of early recognition and lead to improved patient survival. PMID- 2921460 TI - Limiting medical care: the cogency of physicians. PMID- 2921461 TI - Serum erythropoietin in healthy older persons. PMID- 2921462 TI - Risk disclosure for mammography in the elderly. PMID- 2921463 TI - Do methodological problems negate findings of important nursing home studies? PMID- 2921464 TI - The use of depression rating scales. PMID- 2921465 TI - What's really the problem in nursing homes? PMID- 2921466 TI - Massive diflunisal overdosage with recovery. PMID- 2921467 TI - The treatment of major depression in older and younger psychiatric inpatients. PMID- 2921469 TI - Nerve terminal morphology in C57BL/6NNia mice at different ages. AB - The mammalian neuromuscular junction (NMJ) appears to undergo a dynamic remodeling process with advancing age. Previous studies suggest that the NMJ becomes progressively larger with age, to a greater degree in fast-twitch muscles than slow-twitch muscles. To better understand this process, quantitative morphometry was conducted on soleus and extensor digitorum longus (EDL) nerve terminals from C57BL/6NNia mice aged 4, 8, 10, 12, 18, 22, 24, and 32 months. Computer-aided morphometry of camera lucida drawings of aging nerve terminals indicated significant differences in the size and complexity of NMJs in both muscles between different age groups; however, there were no significant net trends with age. The magnitude and direction of the morphometric changes depended on the particular ages compared, and occurred to a greater degree in the EDL. This study is the first comprehensive morphometric study of C57BL/6NNia nerve terminals at so many ages. The results are similar to those obtained for the Fischer 344 rat, and support the hypothesis that nerve terminal remodeling is a dynamic process, not a progressive elaboration. PMID- 2921468 TI - Thermogenic responses of younger and older rats to cold exposure: comparison of two strains. AB - Oxygen consumption and colonic temperatures at rest and during 6 hours at 6 degrees C, body composition, adipose tissue cellularity, and the binding of guanosine 5'-diphosphate (GDP) to isolated brown fat mitochondria were measured in younger (12 months) and older (24 months) male Fischer 344 (F344) and Osborne Mendel (O-M) rats. The rates of resting mass-independent oxygen consumption, the total cold-induced oxygen consumption expressed as body mass-independent (L.kg body mass-.67) or as lean body mass-independent (L.kg lean body mass-.67) did not differ among the four groups. Although the absolute (g) and the percentage of carcass mass as lean body tissue did not differ within the strains, these measures were significantly greater in the younger and older O-M rats compared to the F344 counterparts. In contrast, cold-exposed O-M rats showed significantly greater total specific GDP binding to isolated brown fat mitochondria than did the O-M animals (an index of brown fat thermogenic capacity); GDP binding did not differ between 12 and 24 months in either strain except when expressed in terms of body mass to the 0.67 power. In general, the results presented here showed no significant age-related loss in oxygen consumption in either strain. However, there did appear to be strain-related differences in brown fat mitochondrial GDP binding, and body composition. PMID- 2921470 TI - Age as a predictor of diagnostic and initial treatment intensity in newly diagnosed breast cancer patients. AB - Newly diagnosed breast cancer patients (N = 494) aged 45-90 years were studied to determine if age was associated with appropriate diagnostic and prognostic evaluations, and initial definitive therapy. Women 75 years of age and older were less likely to receive an appropriate diagnostic evaluation than were younger women, but age was not associated with an appropriate prognostic evaluation. Older patients with local disease who were undergoing lumpectomy were less likely to receive follow-up radiation; older patients with regional disease undergoing mastectomy were less likely to receive adjuvant chemotherapy (including hormonal therapy). Physicians' attitudes about appropriateness of therapy appear to be the major determinant of what treatment is received. PMID- 2921471 TI - Aging and gastrin production: changes in serum and antral gastrin concentrations in the rat. AB - Serum gastrin concentration and antral gastrin content were measured in 4-5- and 26-28-mo rats under fed conditions, after 3 days of starvation, and after 1 day of refeeding after starvation, to determine whether gastrin homeostasis is altered during aging. Gastric weight was 29% greater, but antral weight and DNA were less in the older rats. Serum gastrin fell during starvation and rose during refeeding in both groups, but it was lower in aging rats only during refeeding. Antral gastrin content in older animals was 60% of that in young rats. Starvation reduced antral gastrin only in the young, whereas refeeding lowered antral gastrin in the older animals. We conclude that, in aging rats, the relationship of serum and antral gastrin is altered during changes in food intake. PMID- 2921472 TI - Studies in the distribution of body fat: I. Effects of age, sex, and obesity. AB - The pattern of body fat distribution has been shown to be related to a large number of variables of clinical importance. A variety of indices have been devised, many of them simple enough to be useful in large-scale clinical studies. Relationships among these several indices and systematic information on the effects of age, sex, and obesity have, however, not been systematically studied. Five anthropometric ratios that classify individuals into different body types have been computed for 1179 men and women aged 17-96 years. These are: waist hip ratio, arm thigh ratio, waist thigh ratio, waist arm ratio, and subscapular triceps skinfold ratio. In general, the age patterns show progressive trends toward increasing upper and central body fat deposition with age. In women there tends to be a postmenopausal acceleration of this trend. The ratios are distinctly higher in men than in women and are also independently influenced by the body mass index. Predictive equations that take age and BMI into account for each of the indices for men and women have been provided. PMID- 2921473 TI - Age and simple reaction time: decade differences for 5,325 subjects. AB - In a booth at a public exhibition entitled "Medicines for Man," 5,325 men, women, and children carried out a 1-minute test of simple reaction time (RT) with 1 to 10 second randomized variable preparatory interval (PI). They recorded their ages by decade. Average RT over the last eight (of ten) trials increased progressively from the 20s up to age 60 and over, and downward to the teens and under 10s. The single fastest RT in each test varied much less with age, only the 20s being clearly faster than the rest, with the under 10s slower. Within-subject variability of RT was increased only in the under 10s and over 60s. Ability to sustain attention during the longer PIs may underlie the gross average RT differences with age, and possibly some more basic neural property the superiority of the 20s in fastest RT. PMID- 2921474 TI - Influence of sentence context on speech perception in young and older adults. AB - This study investigated the ability of young and older adults to use contextual cues to understand speech in ordinary listening situations. Key word recognition scores were obtained with the Speech Perception in Noise (SPIN) test. Sentence lists contained 50 key words preceded by a high predictability (HP), low predictability (LP), or a carrier phrase (CP) context accompanied by a varying background of multitalker babble. Comparison of the low context items vs the number of meaningfully rich items correctly identified provided an index of the listener's ability to use contextual information in the HP sentences. The LP and CP score reflected the individual's ability to recognize items based only on the acoustic-phonetic information of the key words. Most individuals were able to take some advantage of contextual cues in everyday sentences; however, the older listeners were more adversely affected by background noise than younger listeners. For clinical utilization of the SPIN test, further research is needed to develop normative data as a function of age to make it an "age-fair" test. PMID- 2921475 TI - Data quality and age: health and psychobehavioral correlates of item nonresponse and inconsistent responses. AB - This study examined item nonresponse and inconsistent responses (IRs) and their health and psychobehavioral correlates in a population-based survey of adults 65 years and older. We administered an in-person questionnaire concerning physical, social, and psychological health to 1,155 men (mean age = 73.7 years) and 1,942 women (mean age = 74.8 years). Nonresponse rates varied with item topic, and "don't know" (DK) responses were more common than refusals. DKs increased with age of respondent, tended to be more common in women than men, and were associated with poorer physical, cognitive, and psychological functioning. Conversely, IRs increased with age among men but not women, but were also associated with poorer physical, cognitive, and psychological functioning. Results are discussed in terms of motivational and attentional factors, and their implications for survey research with the frail elderly and very old are noted. PMID- 2921476 TI - Absence of depression in elderly adults. AB - Depressive symptomatology has been reported to be most prevalent over the age of 65. This study examined the effects of age (young less than or equal to 60 years, old greater than 60 years) and sex on the Beck Depression Inventory (BDI), MMPI Scale 2 (Depression), and Geriatric Depression Scale (GDS). Responses to somatic versus psychological complaints on the BDI were examined separately, and the physical malfunctioning subscale (D3) of the MMPI-2 was also evaluated. No age effects were found on any of the depression scales' total scores. On the BDI, the older group reported more somatic complaints than the younger group. Psychological complaints were reported equally for young and old groups. Women reported more depressed items on the MMPI-2 and reported a greater number of symptoms of physical malfunctioning (D3) than men for both age groups. No age by sex interaction reached significance. A report of greater physical malfunctioning (D3) was significantly associated with higher scores on all the depression scales. The increased prevalence of somatic complaints on self-report depression scales probably results in higher scores, which are misinterpreted as representing more depression in the elderly population. It is recommended that a depression scale such as the GDS, which excludes somatic items, be used to assess depression in older adults. PMID- 2921477 TI - Effects of sensory and motor functioning on adult intellectual performance. AB - This study examined longitudinal health and intelligence data to determine whether sensory or motor deficits account for some of the age-related intellectual changes that are commonly seen from midlife onward. Although sensory and motor functioning did not account for the age-related decrements in performance on speeded, visual perceptual tasks found for this sample in previous work, we did find that hearing deficits added error variance to performance estimates on two verbal subtests of the Wechsler scales. PMID- 2921478 TI - The home environments of older people: a description of the psychosocial processes linking person to place. AB - This study describes how older people endow the home environment with meaning. Specifically, it describes the nature and meaning of the linkages between the older individual and the home environment, suggesting that the home environment is given meaning through three classes of psychosocial processes relating the person to (a) the sociocultural order, (b) the life course, and (c) the body. Seven discrete components of the processes are illustrated, using extensive case examples derived from lengthy ethnographic interviews with seven elderly informants. In the context of the relationship of the individual to culture, the study assumes the salience of personal meaning as a significant level of analysis. PMID- 2921479 TI - Elderly persons living alone: the effect of community context on living arrangements. AB - Current explanations of elderly household composition focus largely upon individual demographic, economic, and health characteristics and frequently ignore the effects of the community context within which elderly persons live. In this study, we incorporate the community context into an aggregate explanation of intermetropolitan variation in rates of living alone among elderly persons. We contend that three crucial community resources influence the rate of living alone: demographic and normative environment, economic affordability, and community social services. Data for Metropolitan Statistical Areas in the United States in 1980 provide initial support for this community-level explanation of elderly household composition. PMID- 2921480 TI - Home care for elderly persons: linkages between formal and informal caregivers. AB - Prior research has generally focused on characteristics of elderly persons that predict contact with community services or the volume of services used. In contrast, this study investigates how personal care and home health services are used in relation to assistance from primary kin caregivers. A typology was developed based on task sharing or segregation between kin caregivers and service providers, and four types of informal-formal linkages around these tasks were identified: kin independence, formal service specialization, dual specialization, and supplementation. Findings regarding predictors of the types showed that caregiver and care recipient need variables were most significant in differentiating among them, although caregiver gender also had some discriminatory power. PMID- 2921481 TI - Measuring the communication of social support from adult children. AB - Further knowledge of the nature and significance of the relationships of elderly persons to their adult children requires the application of social support scales tapping the quality and content of their interactions. Scaling efforts must further address conceptual and operational specification, the differentiation of sources and dimensions of support, the objectification of self-report scales, and construct validity. Respondents to this survey are a community, stratified probability sample of adults aged 50 and older (N = 1,174). Measures employed include 2 items reflecting instrumental support and 17 items designed to tap Cobb's (1976) definition of expressive support as consisting of information that one is loved, esteemed, and embedded in a social relationship characterized by mutual caring and obligation. Factor analyses consistently discern one instrumental and three expressive dimensions of support: Caring and Concern, Social Integration, and Love and Affection. These subscales are differentially correlated with sociodemographic characteristics of the parents and adult children, as well as with depression and disability. Implications of these and other findings are discussed. PMID- 2921482 TI - An examination of loneliness among elderly Canadian seasonal residents in Florida. AB - As part of a larger study focusing on different facets of the lives of 2,731 older Canadians who seasonally reside in Florida, we investigated primarily the extent of family and friendship contacts and the loneliness expressed by these older Canadians. The data were collected using a questionnaire that was distributed and returned by mail. The sample was taken from the subscription list of a newspaper in Florida that was a subsidiary of a large Canadian newspaper. The results show a population that was relatively young, married, in generally good health, and with rather extensive contacts with family and friends while residing in Florida. Nevertheless, more than a fifth indicated they were at least somewhat lonely. Results, using discriminate function analysis, showed that those more lonely were younger, female, less educated, not married, in poorer physical health, had fewer Florida friends, and had more children who lived near them in Canada, but fewer children who lived near them in the United States. Implications of the results are discussed. PMID- 2921483 TI - Puzzles in the epidemiology of colon cancer. PMID- 2921484 TI - The value of Chiba fine-needle aspiration biopsy in the diagnosis of hepatic malignancy: a comparison with Menghini needle biopsy. AB - The detection or exclusion of metastatic liver involvement is critical in the management and prognosis of patients with malignant disease. Noninvasive imaging modalities such as computed tomography, ultrasound, and technetium colloid liver scan are highly sensitive but nonspecific. Serum alkaline phosphatase is of similar value. A blind liver biopsy by the Menghini technique is often done to confirm the diagnosis, but its yield is low. We prospectively evaluated 74 patients using blind Menghini needle biopsy and concurrent Chiba fine-needle aspiration biopsy (FNAB) techniques. A positive diagnosis of malignancy was made in 30 patients (41%). In only 25 (34%) was the diagnosis made by Menghini biopsy, while Chiba FNAB confirmed the diagnosis in all 30 patients. Thus, concurrent use of both needles increased the diagnostic accuracy by 7%. Seven additional patients, considered to have one or more contraindications for the Menghini biopsy, underwent Chiba FNAB alone; the diagnosis was confirmed in all without complication. We conclude that FNAB alone or in combination with Menghini biopsy is valuable and safe in the diagnosis of metastatic liver disease. PMID- 2921485 TI - Gastric epithelial polyps. A 10-year study. AB - We have reviewed the 10-year experience of a community teaching hospital with gastric epithelial polyps and have analyzed 121 polyps removed from 35 patients. Hyperplastic polyps constituted nearly 75% of the polyps examined; fundic gland polyps constituted 17%, and adenomatous polyps were infrequent (8.6%). No clinical or endoscopic finding distinguished the variants of polyp before histologic examination. The majority of hyperplastic and fundic gland polyps were multiple. Whenever there were multiple polyps, all polyps were of the same histologic type. In no case did adenocarcinoma originate within a benign polyp. In only a single case was there an associated adenocarcinoma elsewhere in the stomach. None of the adenomatous polyps was linked with gastric adenocarcinoma. PMID- 2921486 TI - Delayed cholescintigraphy in the diagnosis of unilateral hepatic duct obstruction in the nonicteric patient. PMID- 2921487 TI - Irritable bowel support group: a new form of management. PMID- 2921488 TI - Mechanisms of hypoxemia during panendoscopy. AB - Hypoxemia during esophagogastroduodenoscopy (EGD), or panendoscopy has been generally attributed to sedation. We studied 49 patients ranging in age from 17 to 71 years with normal or nearly normal lung function undergoing EGD to determine the effects of sedation and the effects of the endoscope on arterial oxygen saturation (SaO2). All patients received intravenous diazepam and 41 also received meperidine. EGD was delayed 10.7 +/- 7.5 min after intravenous diazepam administration in the 42 group 1 patients. Seven patients underwent EGD within 2 min of receiving intravenous diazepam (group 2). Ventilation decreased after diazepam, recovered, then decreased immediately after endoscope insertion in the group 1 patients. Periods of hypopnea, up to 39 s long, were observed during EGD. The average decrease in SaO2 was 4.0% after diazepam (p less than 0.0001). SaO2 returned to the pre-EGD level, then decreased 2.4% during EGD (p less than 0.0005). Maximum SaO2 decrease occurred 27 +/- 6 s after insertion of the endoscope then rapidly recovered. There was a linear correlation between the duration of hypopnea and maximum SaO2 decrease (r = 0.84, p less than 0.001). All group 2 patients experienced a period of hypopnea (13.3 +/- 9.6 s) and SaO2 declined 9.0%. The SaO2 decline was significantly greater in the group 2 subjects (p less than 0.0001). Our results confirm previous findings that intravenous sedation causes hypoventilation and hypoxemia. Moreover, hypoventilation and further arterial oxygen desaturation are caused by either the mechanical effect of the endoscope or a reflex stimulated by it. PMID- 2921489 TI - Is the gastrin response to secretin provocation a function of antral G-cell mass? Results in the hypergastrinemia of acid hyposecretion. AB - Some patients with hypergastrinemic achlorhydria may have false-positive secretin provocation as an exaggeration of the normal gastrin response to secretin, presumably related to an increased, or more responsive, antral G-cell mass. To test this hypothesis, we reviewed our experience with secretin provocation in normogastrinemic subjects with presumed normal antral G-cell mass (normal--17, duodenal ulcer--13) and in patients with hypergastrinemia related to changes in antral G-cells (vagotomy--5, hypochlorhydria--7, achlorhydria--10). Basal serum gastrin (mean +/- SEM) was progressively higher for each group; normal (42 +/- 3 pg/ml), duodenal ulcer (53 +/- 4 pg/ml), vagotomy (226 +/- 54 pg/ml), hypochlorhydria (346 +/- 92 pg/ml), achlorhydria (844 +/- 100 pg/ml). On selective analysis of only those with gastrin rises, significant differences (p less than 0.05) in peak gastrin change were found between achlorhydria (93 +/- 21 pg/ml) compared with all other groups and between hypochlorhydria (40 +/- 12 pg/ml) versus normal (6 +/- 1 pg/ml). Linear regression in these responders showed a significant correlation (p less than 0.001) between basal gastrin and peak gastrin change after secretin. There were no false-positive secretin provocation tests, but four achlorhydric patients had gastrin rises greater than 100 pg/ml, whereas no patient in the other categories had rises above 90 pg/ml. Our results support the concept that patients with hypergastrinemic achlorhydria tend to have greater G-cell responsiveness to secretin provocation, which may account for the false-positive results in some such patients. PMID- 2921490 TI - Fibrinous pericarditis in alcoholic liver disease. AB - The autopsy data at the University of Southern California Liver Unit was studied during a 6-year period to investigate the relationship of fibrinous pericarditis with liver diseases. We found 18 cases of fibrinous pericarditis in 220 patients with alcoholic liver disease but none in 32 patients with fulminant and subacute hepatitis without alcoholism or in 39 patients with nonalcoholic cirrhosis. Although all the 18 patients with pericarditis had azotemia, 3 patients had pericarditis develop only in mild renal function impairment. These findings suggest that chronic alcoholism may precipitate pericarditis during the hepatorenal syndrome. PMID- 2921491 TI - Transient esophageal obstruction after pneumatic dilation for achalasia. AB - We report what we believe to be the first patient in whom an esophagram immediately after a routine, uncomplicated pneumatic dilation revealed complete esophageal obstruction. With conservative medical therapy, the obstruction spontaneously resolved within 48 h, and total relief of dysphagia followed. Other reports have told of distal narrowing and slow emptying of the esophagus after pneumatic dilation. Most of these patients had a good therapeutic result. Hence, partial or complete esophageal obstruction after pneumatic dilation does not by itself represent evidence of treatment failure. PMID- 2921492 TI - Benign pneumoperitoneum in a patient with celiac sprue. AB - A patient with celiac sprue was found to have an asymptomatic pneumoperitoneum. Prompt recognition that the pneumoperitoneum was due to pneumatosis cystoides intestinalis prevented unnecessary surgical intervention. Severe mucosal disease of the small intestine can be associated with an asymptomatic pneumoperitoneum. PMID- 2921493 TI - Multifocal adenocarcinoma of the proximal small intestine in a patient with celiac sprue. AB - Adenocarcinoma of the small intestine is a known complication of celiac sprue. We report a 63-year-old man with a history of celiac disease who developed anemia, guaiac-positive stools, and jaundice. Five discrete adenocarcinomas of the proximal small intestine were identified over a 9 year period. Endoscopic retrograde cholangiopancreatographic (ERCP) and radiographic evaluation of the small bowel were helpful in diagnosing adenocarcinoma involving the ampulla of Vater and jejunum. This case demonstrates for the first time the multifocal, malignant potential of sprue. It also illustrates the importance of an aggressive, systematic work-up of patients whose course has changed despite dietary restriction. PMID- 2921494 TI - Hemangiosarcoma of the rectum after chronic anorectal ulceration. AB - A 37-year-old man with a 30-year history of recurrent anorectal ulceration developed a hemangiosarcoma of the rectum. This diagnosis was made based on histology and immunocytochemistry. We believe this is the fifth reported case of hemangiosarcoma of the rectum and is another example of a rare granulation tissue sarcoma. PMID- 2921495 TI - Lumping and splitting through thick and thin bowel. PMID- 2921496 TI - Sigmoid volvulus as a complication of ileal Crohn's disease. AB - Intestinal volvulus in patients with Crohn's disease is rare and we could find only one report of sigmoid volvulus with active Crohn's colitis. We have seen a 54-year-old woman with long-standing Crohn's disease who developed large-bowel obstruction. After eventual detorsion of the sigmoid volvulus, we found that her ileum was involved with active Crohn's disease and that her colonic mucosa was free of mucosal lesions. In this case, we suspect that the reactivation of the ileal Crohn's disease as well as other features commonly associated with Crohn's disease contributed to the development of sigmoid volvulus by causing fixation, torsion, and dilatation of distal bowel. PMID- 2921497 TI - Spontaneous rupture of the liver associated with amyloidosis. AB - Fatal spontaneous rupture of the liver is described in a 46-year-old women with hepatic amyloidosis diagnosed premortem by liver biopsy. An autopsy revealed systemic amyloidosis, with no evidence of an underlying chronic inflammatory condition, infection, or immunocyte dyscrasia. By computerized search, this is only the third reported case of spontaneous rupture of the liver complicating amyloidosis. PMID- 2921498 TI - Pseudo-Budd-Chiari syndrome: extrinsic deformity of the intrahepatic inferior vena cava mimicking membranous obstruction. AB - Budd-Chiari syndrome secondary to membranous obstruction of the intrahepatic inferior vena cava is a treatable form of chronic liver disease. I report a patient with portal hypertension in whom distortion of the inferior vena cava by cirrhosis and increased intraabdominal pressure initially suggested this condition. The correct diagnosis was made by obtaining lateral views during inferior vena cavography, which demonstrated a tapered, rather than membranous, obstruction, along with normal hepatic venous anatomy and pressure and markedly increased portal vein pressure during transhepatic puncture with a thin needle. That extrinsic deformity of the inferior vena cava may mimic membranous obstruction has not been emphasized recently. This distinction is important as surgical membranotomy is not indicated in patients with cirrhosis and secondary deformity of the inferior vena cava. PMID- 2921499 TI - Low-dose ursodeoxycholic acid prolongs cholesterol nucleation time in gallbladder bile of patients with cholesterol gallstones. AB - The high rate of stone recurrence represents a drawback of non-surgical therapy of cholesterol gallstone disease. Although most studies report that long-term bile acid treatment does not have protective effects, preliminary results suggest that low-dose ursodeoxycholic acid decreases the rate of gallstone recurrence in a subgroup of younger patients. To clarify the underlying mechanism we investigated whether low-dose ursodeoxycholic acid treatment influences biliary cholesterol saturation and/or nucleation time of cholesterol. Ten patients with cholesterol gallstones and functioning gallbladder received 250 mg ursodeoxycholic acid/day at bedtime 6-10 days prior to cholecystectomy. Eleven patients with cholesterol gallstones without treatment served as controls. Cholesterol crystals were present in the gallbladder bile of 7 out of the 10 patients receiving ursodeoxycholic acid and in all control biles. Ursodeoxycholic acid treatment significantly (P less than 0.02) decreased the cholesterol saturation index (mean +/- S.E.: 0.94 +/- 0.05 vs. 1.43 +/- 0.18) and led to an approximately 5-fold prolongation (P less than 0.005) of the cholesterol nucleation time (mean +/- S.E.: 12.0 +/- 2.4 vs. 2.3 +/- 0.7 days). We conclude that low-dose ursodeoxycholic acid might be effective in the prevention of post dissolution gallstone recurrence by both decreasing cholesterol saturation and prolonging cholesterol nucleation time. PMID- 2921500 TI - Bile salts and hydrodynamics of bile formation. AB - We report a novel method to assess bile secretory pressure using a Statham pressure transducer. The studies were performed in vivo in male Sprague-Dawley rats under pentobarbital anesthesia. Maximal secretory pressure averaged 21.8 +/- 1.1 (S.D.) cmH2O. The bile accumulated after 10 min of obstruction was 7.7 +/- 2.8 microliters.g-1; assuming a basal biliary dead space of 2.3 microliters.g-1, the distended capacity of the biliary tree averaged 10 microliters.g-1. The small volume of the strain gauge permitted calculation of compliance of the biliary tree which averaged 0.35 +/- 0.12 microliters.cmH2O-1.g-1. Stimulation of bile flow by bile salts reduced the time required to reach maximal bile secretory pressure. Taurocholate but not taurodehydrocholate decreased maximal secretory pressure within minutes, the pressure-time curves showing a new equilibrium between bile formation and regurgitation forces. Both bile flow and bile salt recoveries were decreased by taurocholate but not by taurodehydrocholate. Taurocholate decreased biliary compliance while taurodehydrocholate had no effect. This provides further evidence that taurocholate increases the biliary permeability and suggests that this bile salt also affects the elastic properties of the biliary tree. PMID- 2921501 TI - Retinol and retinyl esters in patients with alcoholic liver disease. AB - Liver retinoid levels and the retinyl esters were examined in liver biopsy specimens from 70 patients with alcoholic and nonalcoholic liver diseases. There was a wide variation in the liver retinoid levels. The liver retinoid level was statistically significantly lower in 15 patients with alcoholic liver disease and a depressed Normotest (NT) value of less than 65% compared with patients with alcoholic liver disease and a normal NT value of greater than 65% (P less than 0.01). The mean serum retinol level in patients with alcoholic cirrhosis was 0.68 +/- 0.38 mumol/l compared with 1.99 +/- 1.14 mumol/l in patients with alcoholic fatty liver (P less than 0.03). The relative amount of retinyl oleate was increased in the alcoholic fatty liver compared with the nonalcoholic fatty liver (P less than 0.001). PMID- 2921502 TI - Dimethylnitrosamine-induced cirrhosis. Evidence for an immunological mechanism. AB - The present study is concerned with the early events associated with the development of cirrhosis induced by dimethylnitrosamine (DMN). The antigenic expression of MHC class II components (Ia) and of some intermediate filament proteins (vimentin and desmin) have been studied by immunohistochemistry and the findings correlated with ultrastructural data. Micronodular cirrhosis developed after 3 weeks of treatment with DMN but enhanced expression of Ia antigen on macrophages and on infiltrating lymphocytes was observed after 1 week, before the formation of septa, suggesting that immune-mediated mechanisms are involved in the response to DMN-induced liver injury. The expression of vimentin and of desmin also increased at an early stage and at 3 weeks the septa were outlined by cellular elements showing positivity for both intermediate filament proteins. In keeping with these observations, ultrastructural data showed active division of macrophages in situ, infiltration of the parenchyma by T and B lymphocytes, activation of lipocytes (Ito cells) showing evidence of mitosis, and the presence of transitional elements between lipocytes, myofibroblasts and fibroblasts. This experimental model may be helpful in understanding the relationship between immune-mediated response to liver injury and development of hepatic fibrosis. PMID- 2921504 TI - The role of sinusoidal stenoses in portal hypertension of liver cirrhosis. AB - To investigate the significance of sinusoidal stenoses in portal hypertension, liver cirrhosis was produced by feeding a choline-deficient diet for 6 months in rats, and hepatic haemodynamics were examined in the cirrhotic rats before and after feeding ordinary rat pellets for another 2 months. Feeding ordinary rat pellets led to the disappearance of fat droplets accumulated in the hepatocytes, normalization of the size of the swollen hepatocytes, and recovery from sinusoidal stenoses. As a result, increased sinusoidal vascular resistance and elevated portal vein pressure were reduced markedly, and clinical signs of portal hypertension, ascites and collateral blood circulation around the liver improved prominently. These facts suggest that sinusoidal stenoses lead to an increase in hepatic vascular resistance and portal hypertension. PMID- 2921503 TI - Methionine enkephalin is increased in plasma in acute liver disease and is present in bile and urine. AB - Plasma immunoreactive methionine enkephalin is increased in cirrhosis. To determine whether it was increased in acute liver disease and chronic renal failure and whether the peptide was present in bile and urine, it was measured by radioimmunoassay in appropriate samples. Plasma immunoreactive methionine enkephalin, while at its peak in 15 patients with acute liver disease (median 425 pmol/l, range 220-1460), was approximately six times greater (P less than 0.001) than in 15 patients with chronic renal failure (70 pmol/l, 50-140), 15 controls with other diseases (75 pmol/l, 50-115) and 15 healthy controls (65 pmol/l, 50 95). In eight of the patients recovering from acute liver disease, the decline of the peptide's plasma level correlated with that of the alanine aminotransferase (r = 0.813, P less than 0.01) and prothrombin time (r = 0.682, P less than 0.05) measured in the simultaneously taken blood. Immunoreactive methionine enkephalin was found to be excreted in bile and urine. The possibility that increased plasma methionine enkephalin, and possibly other opioid peptides, may contribute to some of the manifestations of acute liver failure is worthy of further investigation. PMID- 2921505 TI - The effect of portal diversion upon function of the reticuloendothelial system and upon plasma fibronectin levels. AB - A previous publication suggested that for 9 weeks after portal diversion in dogs, there were no changes in reticuloendothelial function assessed by measurement of t1/2 or phagocytic index of reticuloendothelial test lipid emulsion. The present study was conducted in rats over 18 weeks. It was observed that the phagocytic index decreased and the t1/2 lengthened at 18 weeks after either portacaval shunt or portacaval transposition and that plasma levels of fibronectin were elevated four- or five-fold after either form of diversion, whilst only being elevated two fold after sham operation. There was an increase in portacaval shunt rats in liver tissue distribution of administered lipid emulsion when tested between 6 and 12 weeks post-operatively which then returned towards normal. The activity in portacaval transposition and sham-operated rats was unaltered. These studies suggest that the delay in clearance of administered particles in portacaval shunt and portacaval transposition rats is related to the portal diversion rather than to altered blood flow and thus the finding is of relevance in patients with cirrhosis who also have significant portacaval shunting. PMID- 2921506 TI - Treatment of protracted acute type B hepatitis with recombinant alpha-A interferon. A pilot study. AB - Six individuals with protracted acute type B hepatitis were treated with recombinant alpha-A-interferon for 12 weeks. Two females eliminated the HBV completely, while 4 males did not respond. Response was preceded by a flare-up of the liver disease. It appears that responses to interferon are not higher in protracted acute type B hepatitis than in progressed chronic active hepatitis B. This assumption has to be proven in larger studies on a statistical basis. PMID- 2921507 TI - Detection of hepatitis B virus core gene products in sera and liver of HBV infected individuals. AB - The C gene of hepatitis B virus (HBV) codes for at least two different proteins (p 21c and p 17e). To investigate the expression of C-gene-encoded proteins in vivo, serum and liver samples from HBsAg-positive patients as well as serial serum samples from an HBV-transfected chimpanzee were studied. Antibodies directed against bacterially synthesized C-fusion proteins were used in Western blots to test for the presence of p 21c and p 17e. In serial serum samples from the chimpanzee, p 21c and p 17e were detected concomitantly during the acute phase of the infection. When sera of patients with chronic HBV infection were studied, all sera containing p 17e were found to be positive also for p 21c. Sera positive for HBV DNA but negative for HBeAg were only positive for p 21c, indicating that HBeAg/p 17e is not an absolutely reliable marker for infectivity. In liver tissue specimens from 20 patients with HBV-related liver diseases, p 21c was detected in five cases, indicating viral replication. The p 17e antigen, however, was present only in low amounts in three of these five, suggesting that synthesis of p 21c and p 17e is not strictly coupled. C/Pol-gene-encoded fusion proteins were found in the liver tissue of only one patient with cirrhosis, supporting our previous finding that detectable levels of these proteins are expressed rarely. PMID- 2921508 TI - Coproporphyrinogen oxidase, protoporphyrinogen oxidase and ferrochelatase activities in human liver biopsies with special reference to alcoholic liver disease. AB - The activities of coproporphyrinogen oxidase, protoporphyrinogen oxidase and ferrochelatase have been assayed in human liver biopsies using recently developed highly sensitive specific enzyme assays. The specific activities (nmol/min/mg protein) in controls were 0.010 +/- 0.003 (mean +/- S.D., n = 11), 0.18 +/- 0.07 (n = 9) and 0.062 +/- 0.022 (n = 8), respectively. The total activities (mumol/min/liver) were determined, using ultrasound to determine liver volumes, and were 2.6 +/- 0.6 (n = 5), 36.6 +/- 13.9 (n = 6) and 14.2 +/- 5.4 (n = 3), respectively. Both specific and total enzyme activities in alcoholics with fatty liver were not significantly different from normal controls. Decreased protoporphyrinogen oxidase activity (0.08 nmol/min/mg protein or 20.2 mumol/min/liver) was found in two patients with variegate porphyria. In a patient with erythrohepatic protoporphyria a reduction of the ferrochelatase activity (0.01 nmol/min/mg protein) was demonstrated. PMID- 2921509 TI - Inheritance of retarded forebrain commissure development in fetal mice: results from classical crosses and recombinant inbred strains. AB - Deficiency of the adult corpus callosum in BALB/c mice shows incomplete penetrance and is clearly polygenic, whereas the defect in fetuses shows complete penetrance and a much less complex mode of inheritance. Retardation of the growth of the corpus callosum and the hippocampal commissure in the fetal mouse forebrain was expressed by a standard score (z) derived from body weight, such that a fetus with a score less than -2.0 was held to have commissures abnormally small for the body size. By this index, almost all C57BL/6 fetuses were normal, whereas BALB/c fetuses in the body weight range 0.5 to 1.0 g were often 5 standard deviations below the expected value of 0.0. In classical crosses between C57BL/6J and BALB/cWah, inheritance of the index of abnormality (z) was recessive, and about half of the fetuses in backcrosses to BALB/c were below 2.0. However, the distribution of scores was not bimodal. The results were consistent with a two-locus but not a single-locus difference between parent strains. Among the seven recombinant inbred strains derived from the By strains of C57BL/6 and BALB/c, there were three or possibly four distinct clusters of strains, which also suggested two-locus inheritance and excluded a single-locus difference. Although substantial retardation of commissure growth was evident in fetuses, deficiency or absence of the corpus callosum in weanling and adult By recombinant inbred mice was extremely rare in all strains except BALB/cByJ. These data confirm anatomical results showing that, in all but the most extremely retarded cases, the corpus callosum recovers from an obvious prenatal defect. PMID- 2921510 TI - EMS-induced mutations in Anopheles quadrimaculatus (Say), species A. AB - Three new mutants were induced in a laboratory strain of Anopheles quadrimaculatus (Say), species A, by feeding adult males ethyl methanesulfonate (EMS). Rose eye (ro) is a recessive X-linked trait. Short antenna (Sa) and melanotic (Mel) are dominant autosomal traits that are lethal in the homozygous condition. Linkage crosses and X-autosome translocations were used to assign short antenna to the right arm of chromosome 3 about 45 map units proximal to stripe (st+), and melanotic was located on chromosome 2 near the centromere. PMID- 2921511 TI - Microphthalmia: a new recessive mutation in the Norway rat. PMID- 2921512 TI - Evidence of mendelian inheritance of the nucleolar organizer regions in the Spanish common rabbit. PMID- 2921513 TI - Persistent pulmonary hypertension of the newborn. PMID- 2921514 TI - Hypertension as the presenting problem in primary hypothyroidism. PMID- 2921515 TI - Section 89--no relief in sight. PMID- 2921516 TI - How to manage multiple insurance plans. PMID- 2921517 TI - The drama of the 1989 legislative session begins to unfold. PMID- 2921518 TI - The general internist: is he the gatekeeper of the medical care system or the doormat? PMID- 2921519 TI - Expression of viral and virus-like elements in DNA repair deficient/immunodeficient "wasted" mice. AB - Wasted mice bear an autosomal recessive mutation (wst) that causes neurologic abnormalities, faulty DNA repair in lymphocytes, and immunodeficiency at mucosal sites. Recent work has suggested possible viral involvement in these manifestations by demonstrating abnormal viral gp70 expression that segregates with the wasted mutation. In the experiments reported here, we examined tissue specific expression of AKR viral (AKV) sequences and virus-like 30S (VL30) elements in wasted and control mice. Our studies showed that AKV and VL30 RNA expression were two- to fivefold higher in spleen, brain, and thymus of mice bearing the wst allele than in those of control mice. (These tissues have all been shown to display functional or developmental abnormalities in wst/wst mice.) Expression of viral mRNA in Peyer's patches and mesenteric lymph nodes was similar in wasted and control animals. The majority of the VL30-hybridizing RNA in all tissues could be attributed to long-terminal-repeat rather than to main body sequences. These differences in expression between wasted and control mice could not be attributed to differences in VL30 or AKV gene copy number. Our results demonstrate an association between altered expression of viral and virus like sequences and the development of tissue-restricted abnormalities in wst/wst mice. PMID- 2921520 TI - Intravenously injected sialidase inactivates attachment sites for lymphocytes on high endothelial venules. AB - Blood-borne lymphocytes initiate entry into secondary lymphoid organs, such as peripheral lymph nodes (PN) and gut-associated Peyer's patches (PP), by a highly specific adhesive interaction between the lymphocytes and the endothelium of specialized blood vessels known as a high endothelial venules (HEV). The selectivity with which functional subpopulations of lymphocytes migrate into particular lymphoid organs is believed to be regulated by the expression of cell adhesion receptors and complementary ligands on lymphocytes and HEV, respectively. The entry of lymphocytes into PN and PP has clearly been shown to involve distinct receptor-ligand pairs. Employing the Stamper-Woodruff in vitro adhesion assay, which measures lymphocyte attachment to HEV in cryostat-cut sections of lymphoid organs, we have previously shown that treatment of PN sections with two different sialidases inactivates HEV-adhesive ligands, whereas treatment of PP tissue sections has no effect on HEV-adhesive function. We now report that in vivo exposure of HEV to sialidase (after i.v. injection of the enzyme) also selectively prevents subsequent in vitro attachment of lymphocytes to PN HEV but not to PP HEV. Consistent with this organ-selective impairment of HEV-adhesive function by sialidase, i.v. injection of the enzyme is shown to prevent short term lymphocyte accumulation within peripheral lymph nodes while having no significant effect on accumulation in PP, blood, or nonlymphoid organs. Histologic examination with the sialic acid-specific lectin from Limax flavus verified that i.v. injected sialidase effectively removes stainable sialic acid moieties from HEV in both PN and PP. This study confirms that sialic acid is required for the adhesive function of PN HEV-ligands. A role for sialic acid as either a recognition determinant or as a regulatory molecule can be envisioned. In view of the fact that many pathogens release sialidase and cause substantially elevated serum levels of this enzyme, the present observations may have pathophysiologic significance. One mechanism by which such pathogens may avoid destruction is to inactivate susceptible HEV-ligands and disrupt the entry of lymphocytes into lymphoid organs where immune responses against the pathogens would normally be initiated. PMID- 2921521 TI - Purification and amino acid analysis of two human monocyte chemoattractants produced by phytohemagglutinin-stimulated human blood mononuclear leukocytes. AB - Physicochemical characteristics of monocyte chemotactic activity in the culture fluid of PHA-stimulated human mononuclear leukocytes (MNL) were investigated. Among several chemotactic activity peaks eluted from a TSK-2000 gel filtration column, one peak, corresponding to a molecular mass of 17 kDa, accounted for about 40% of total chemotactic activity. On a chromatofocusing column, most of the 17-kDa activity eluted in a pH range of 9.4 to 7.9. It could bind to Orange-A Sepharose. These three characteristics--molecular mass, basic isoelectric point, and dye column binding--were similar to those of human glioma-derived monocyte chemotactic factor (GDCF), recently purified in our laboratory. Therefore, the MNL-derived chemoattractant was purified by the same procedures used for purification of GDCF, namely Orange-A Sepharose chromatography, carboxymethyl (CM)-HPLC, and reverse phase (RP) HPLC. About 50% of the culture fluid chemotactic activity bound to Orange-A Sepharose and was eluted in a single peak by a NaCl gradient. The active pool from the Orange-A column was separated into two sharp peaks by CM-HPLC, each of which eluted at identical acetonitrile concentrations from a RP HPLC column. By SDS-PAGE, the peptides had apparent molecular masses of 15 and 13 kDa and appeared homogeneous. Amino acid analysis showed that the composition of the two peptides was almost identical; and the N terminus of each peptide was apparently blocked. Shared characteristics of these peptides and the GDCF peptides include identical elution patterns from CM- and RP HPLC columns, identical SDS-PAGE migration, almost identical amino acid composition, and blocked N terminus. This suggests that the monocyte attractants isolated from culture fluid of PHA-stimulated MNL are identical to those derived from human glioma cells. PMID- 2921522 TI - Increased regional vascular albumin permeation in the rat during anaphylaxis. AB - The changes in vascular albumin permeation induced by systemic anaphylaxis were studied simultaneously in 21 different tissues of the same animal. Before Ag challenge sensitized rats were injected i.v. with 125I-albumin (test tracer), 51Cr-RBC (vascular space marker) and 57Co-EDTA (extravascular space marker). The index of vascular permeation used was the tissue to blood isotope ratio (tbir), which was obtained by dividing the ratio of 125I/51Cr counts in each tissue by the ratio of the same isotopes in the arterial blood sample. After Ag challenge, the increase in the tbir varied considerably among the different tissues. The most pronounced increase was noted in the lymph node (ninefold) followed by the aorta and mesentery (six- to sevenfold) and the various parts of the gastrointestinal tract (four- to sixfold). In the skin less than skeletal muscle less than lung less than liver and eye two- to fourfold increases occurred. Relatively minor increases in albumin permeation (less than twofold) were observed in the brain less than kidney less than heart and less than spleen. The testis was the only organ in which no significant change occurred. For some of the tissues there was also an increase in the tbir for 57Co/51Cr (an index of the extracellular fluid space) suggesting edema formation. The highest increase was noted in the aorta (fourfold). Minor increases occurred in the atrium of the heart, stomach, duodenum, and lymph nodes. There was also a 36% increase in hematocrit. Therefore, systemic anaphylaxis caused extensive extravasation of albumin and hemoconcentration. PMID- 2921523 TI - The C5-sufficient A/J congenic mouse strain. Inflammatory response and resistance to Listeria monocytogenes. AB - A/J mouse strain poorly responds to an inflammatory stimulus and is highly susceptible to Listeria monocytogenes (Lm) infection. This defect in the phagocyte inflammatory response caused by the C5 component of C deficiency was shown, by linkage analysis, to be the major reason for the extreme susceptibility of A/J mice to Lm infection. The importance of this genetic defect in C5 in relation to the poor macrophage inflammatory response and to the susceptibility to Lm infection was evaluated by developing a C5-sufficient congenic A/J mouse strain. This A/J.C5 mouse strain was studied for its inflammatory response and for its susceptibility to Lm infection. C5-sufficient congenic A/J.C5 mice showed a slight improvement (2X) in their level of macrophage inflammatory response; however, they did not mount an as strong response as the Listeria-resistant C57BL/6J mice which donated the C5 allele. When infected with Lm, A/J.C5 mice were found to be as resistant as C57BL/6J mice. These results suggest that the presence of C5 on an A/J background partially improves the deficient macrophage inflammatory response of that strain. This increase is sufficient to render the A/J.C5 mouse strain highly resistant to Listeria infection. A/J.C5 mouse strain represents a new tool for the study of the importance of C5 in resistance to infection and in the regulation of the macrophage inflammatory response. PMID- 2921525 TI - Molecular analysis of the rat MHC. II. Isolation of genes that map to the RT1.E grc region. AB - An initial mapping analysis of growth and reproduction complex (grc) and grc+ genomic DNA identified several restriction fragment length polymorphisms specific for the grc region of the MHC. To analyze further the genomic organization and structure of the grc, a cosmid library was constructed from a grc+-bearing strain (R21). One cosmid cluster, encompassing 41.4 kb of DNA, contained four, or possibly five, class I genes that mapped to the RT1.E-grc region Two unique non class I fragments were isolated from certain cosmids within this cluster. These fragments were hybridized to genomic DNA derived from five rat strains (BIL/2, R18, R21, R22, and BIL/1), and the results showed that grc-bearing rats have a deletion of at least 3.1 kb of DNA in the region immediately adjacent to the MHC. The loss of the genes in this region is probably the cause of the growth and reproductive defects in these animals and probably also of their increased susceptibility to chemical carcinogens. PMID- 2921526 TI - Antibody secreted by the hybridoma line IIIA4. PMID- 2921524 TI - Developmental regulation of membrane and secretory Ig gamma 2b mRNA. AB - To better understand the developmental regulation of membrane and secretory forms of Ig Heavy chain mRNA, mutations were made in a gamma 2b gene in vitro and assayed for their expression in cell lines representative of early and late stages of B cell development. Processing of the gamma 2b mRNA did not change with the amount of message produced, demonstrating that the production of predominantly secretory mRNA in plasma cells is not the consequence of increased message synthesis. The length of the intron between the secretory and membrane exons was found to affect the relative expression of secretory and membrane mRNA, but this effect was also observed in non-lymphoid cells, suggesting that the intron "gradient effect" does not identify the processing reaction which is regulated during B cell differentiation. Deletion of the signals for the splice from CH3 to the membrane exons resulted in the exclusive production of secretory mRNA irrespective of the developmental stage of the recipient cell, suggesting that this splice reaction plays a role in regulating these mRNA, and that competition between the two polyadenylation sites does not dictate the relative expression of the two forms of message. Appropriate ratios of the two forms were produced from a 2.3-kbp fragment of the gamma 2b gene containing the secretory cleavage and membrane splice signals in the context of a different transcription unit. These results suggest that the changes in the relative expression of secretory and membrane gamma 2b mRNA during B cell development are mediated by a competition between cleavage at the secretory polyadenylation and splicing from CH3 to the membrane exons. PMID- 2921527 TI - Cell-mediated cytotoxicity. A highly sensitive and informative flow cytometric assay. AB - Determination of target cell lysis by cytolytic effectors has typically been achieved by two methods: the release of various markers from the cell, as in 51chromium release assays and the uptake of markers into the cell, as in trypan blue uptake in single cell/conjugate binding assays. Problems associated with these assays might include: (1) poor uptake, (2) nonspecific release, (3) poor statistics, (4) length of assays, or (5) subjectivity. These difficulties prompted the development of a new sensitive flow cytometric assay employing two fluorochromes. PKH-1, a fluorochrome which fluoresces in the green, binds to the cytoplasmic membrane and does not leak or transfer, is used to identify the target cell population. Propidium iodide fluoresces in the red and is used to detect non-viable cells. Use of these two fluorochromes and two parameter analysis allows for identification of four subpopulations in the sample: live effectors, dead effectors, live targets and dead targets. By enumeration of these subpopulations the following information can be calculated: (1) the percent target lysis, (2) effector-to-target cell ratios, (3) viability of the effector cells at the termination of the assay, and (4) viable effector to target cell ratios. The results show that PKH-1 labeling of target cells had no effect on effector-target cell interactions. Excellent correlation was found between this method and the chromium assay, however, due to earlier detection of the lytic event, this method provides a distinct time advantage over current methods. PMID- 2921528 TI - Cross-reaction of antibodies to coupling groups used in the production of anti peptide antibodies. AB - A polyclonal antibody raised against a peptide conjugated using 1-ethyl-3-(3 dimethylaminopropyl)-carbodiimide hydrochloride to maleic anhydride-derivatised lysozyme showed substantial cross-reactivity with m-maleimidobenzoyl-N hydroxysuccinimide ester-derivatised haemocyanin. This was due to antibodies produced against maleic anhydride-derivatised groups on lysozyme that reacted with m-maleimidobenzoyl-N-hydroxysuccinimide ester-derivatised groups on haemocyanin. This observation is important because it is common practice, in the production of anti-peptide antibodies, to use two conjugates. The same peptide is coupled to two different protein carriers by two different coupling methods. One conjugate is used for immunisation and the other for testing the serum. This method assumes that the only antigen common to the two conjugates is the peptide and this was not the case here. A method is described for screening sera which involves affinity purification of the anti-peptide antibody and comparison of binding to the immunogen with that to an appropriate control conjugate. This method avoids the problem of any cross-reaction to coupling groups or proteins. PMID- 2921529 TI - Assays for total and antigen-specific polymeric IgA in serum based on binding to secretory component. AB - Binding assays with secretory component (SC) were used to detect polymeric IgA antibody to E. coli lipopolysaccharide and to estimate total polymeric IgA in sera from 14 patients with alcoholic liver disease and eight normal controls. Radioiodinated human SC was shown to bind to polymeric IgA and IgM but not to monomeric IgA, secretory IgA or IgG. Serum aliquots (0.5 ml) were totally depleted of IgM using 2 ml anti-IgM affinity columns and the effluent sera were titrated in microtitre plates coated with lipopolysaccharide, the binding of polymeric IgA being detected by adding 10 ng radiolabelled SC. Total polymeric IgA was measured via its capacity to inhibit the binding of 5 ng labelled SC to IgM coated wells, quantitation being achieved by comparison with the inhibition produced by purified polymeric IgA. Total lipopolysaccharide-specific IgA antibody was detected by ELISA in sera from both patients and controls, 1185 +/- 793 and 56 +/- 19 U/100 microliters (mean +/- SD), respectively; but polymeric IgA antibody was detected only in patients' sera (131 +/- 214 U/100 microliters). The concentration of total polymeric IgA was higher in patients' sera than in control sera (488 +/- 333 and less than 120 micrograms/ml respectively). PMID- 2921530 TI - A two-particle turbidometric latex immunoassay for the detection of specific IgM antibodies. AB - A simple two stage assay using latex particles as a reaction indicator has been developed for the detection of IgM antibodies to Trichinella spiralis. In the first stage, magnetic polystyrene beads (Dynabeads) coated with T. spiralis antigen were incubated for 30 min with the test serum. After washing, in the second stage, the assay was developed for 1 h using anti-mu-coated latex particles. After sedimentation of the Dynabeads the turbidity of the resultant latex suspension was measured spectrophotometrically at a wavelength of 400 nm. A decrease in turbidity of more than 20% from that of the control, unreacted, suspension was considered positive. Using an IgM phosphorylcholine-binding monoclonal antibody which was reactive with T. spiralis, the sensitivity of the assay was determined to be 110 ng/ml of antibody. This was 20-fold less than the sensitivity achieved in an indirect enzyme-linked immunosorbent assay (ELISA). When the assay was applied to sera obtained from CBA/N or BALB/c mice, which were either normal or immunized against T. spiralis, the expected results were obtained with titers up to 1/640 observed, and confirmed (r = 0.93, P less than 0.001) in the ELISA. PMID- 2921531 TI - What is a safe heat dose which can be applied to normal brain tissue? PMID- 2921532 TI - Characteristics of the response of soft tissue sarcoma to hyperthermia: the correlation between temperature distribution, radiological examination and histology. AB - Nineteen patients with soft tissue sarcoma were treated by a combination modality of hyperthermia and radiation or chemotherapy. There were 26 treatment sites. The size of the tumours ranged from 2.5 x 2 cm to 24 x 26 cm. Hyperthermic treatments were given twice a week, for a total of five to 14 sessions. Twenty-one tumours were treated by hyperthermia combined with radiotherapy, 2 Gy daily, five times a week, for a total of 40-78 Gy. Three tumours were treated by hyperthermia and arterial infusion of adriamycin, 100-120 mg in five or six treatments. For the superficial tumours the complete response rate was 40 per cent, and for the deep seated tumours 6.2 per cent. Among the 12 tumours with no response, nine in which the treatment was evaluated as effective histologically (necrosis of the tumour) and by X-ray CT findings (development of a prominent hypodensity area) were included. Six cases were studied to correlate the X-ray CT findings, angiography and histological findings before and after hyperthermic treatment. The data were also used to interpret the thermal curve. The increased hypodensity area was roughly proportional to the development of necrosis, but there was one case in which hypodensity was not correlated with the necrosis. On the contrary, even in the contrast-enhanced area around the tumour in which the presence of residual tumour was strongly suspected clinically, no tumour cells were visualized. Clinical evaluation of the effect by size of the tumour can be supplemented by CT findings and histology, but should be cautiously adopted. PMID- 2921533 TI - A technique for combining microwave hyperthermia with intraluminal brachytherapy of the oesophagus. AB - A technique for combining microwave hyperthermia with 192Ir brachytherapy for the treatment of oesophageal carcinoma is described. This approach uses an intraluminal afterloading applicator and up to six microwave antennae to deliver both hyperthermia and brachytherapy, with minimal modification of the existing procedure for brachytherapy alone. Each microwave antenna includes a built-in thermistor to control temperature and balance power. Longitudinal temperature distributions were measured in situ from within the applicator, and at the applicator-tissue interface in vivo. Two-dimensional SAR and steady-state temperature distributions measured in muscle-equivalent phantom are presented and discussed. The technique appears to be capable of elevating tissue temperature to greater than 42 degrees C in a radially symmetric volume of length greater than 5 cm, with radial penetration of 0.5 cm. The clinical technique is relatively simple and well tolerated. PMID- 2921534 TI - A microcomputer controlled, local hyperthermia system for uniform tumour heating in unanaesthetized mice. PMID- 2921535 TI - Stability of temperatures during hyperthermia treatments. AB - Attempts to develop a dosimetry for hyperthermia treatments have been limited by problems such as the inability of hyperthermia delivery systems to produce desired temperature distributions and the complexity of modelling complete temperature distributions. However, dosimetric modelling could be simplified if spatial temperature distributions were temporally stable after the treatment's initial heat-up period. In this study, therefore, temporal stability of spatial distributions was examined quantitatively. Hyperthermia was induced electromagnetically. Treatment parameters were documented on surface transparencies. These parameters were kept as constant as possible during treatments, and were reproduced as closely as possible from treatment to treatment. Manual thermometer translation devices facilitated temperature scanning along interstitial catheters. Intra-treatment spatial temperature profiles T(r) of the same catheter were plotted together to characterize each treatment. Time-averaged T(r) of different treatments were plotted together to show inter-treatment variations. Standard deviations sigma T of temperature from average temperature after heat-up were calculated from 302 T(r) obtained from 57 treatments of eight humans and three canines. Over periods of 30-60 min each, the average sigma T of all points scanned was +/- 0.8 degrees C, an order of magnitude less than intratumoral spatial variations of temperature. We conclude that procedures for reproducing treatment parameters led to a desirable extent of temporal stability of temperature during hyperthermia. PMID- 2921536 TI - Effects of hyperthermia on the intracellular pH and membrane potential of Chinese hamster ovary cells. AB - The effects of hyperthermia (exposure to 41-47 degrees C) on the intracellular pH and membrane potential have been studied using Chinese hamster ovary HA-1 cells. Our goal was to determine whether intracellular pH changes or changes in membrane potential correlated with cell killing. The intracellular pH (pHi) was measured using the DMO partitioning technique. A rapid acidification of the intracellular environment was observed at all the elevated temperatures studied. The pHi reached a plateau value of approximately 6.9, and started reversing towards normal values upon prolonged exposure to heat. Similar patterns were seen for delta pH (pHi-pHo). The membrane potential difference (delta psi) was measured using the fluorescence quenching of 3,3-dipropylthio-carbocyanine, and calibrated using a 86Rb+ diffusion potential. We found that delta psi falls to zero only upon prolonged exposure to temperatures above 43 degrees C. When the external pH was changed from normal values the drop in delta psi occurred more readily. Development of thermotolerance resulted in an increase in the time required to make delta psi change by half. The changes in delta psi were shown to be irreversible. When the proton electrochemical gradient (delta mu H+) was calculated using the measured values of delta psi and delta pH, the trends observed were the same as those seen for delta psi. The changes observed for pHi can be accounted for by the changes in the pK values of the components involved in the intracellular buffering. The changes in delta psi and delta mu H+ may reflect the physical breakdown of the transmembrane H+ gradients, which may be the actual mechanical process of cell death. No correlation of cell survival with the measured parameters was observed. PMID- 2921538 TI - Tuning forks: the problem of striking. AB - Tuning fork tests have accompanied us from the beginning of otology. Various methods of striking have been used during the century and the efforts to attain standardization appear to have been forgotten since audiology became available. The article reviews the history of the standardization and throws a new light on the production of overtones and air, compared to bone, conduction frequency. The article stresses the importance of tuning fork testing in clinical practice. PMID- 2921537 TI - Histopathological changes in the spinal cord after 434 MHz microwave hyperthermia in the cervical region of the rat. AB - The time-course of thermal damage to the spinal cord was studied after hyperthermia of the cervical region in the rat. Local 434 MHz microwave heating of the spinal cord (cervical 5-thoracic 2) was obtained by using a ring-shaped applicator. Heat treatment at 42.9 degrees C (+/- 0.4 degrees C) for 38 min resulted in neurological symptoms, ranging from uncoordinated use of the forelegs to paralysis and death in 90 per cent (28/31) of the animals. Histological sectioning of the treated part of the spinal cord was performed immediately, 4, 24 h and 3, 7, 14 and 28 days after hyperthermia. Immediately and 4 h after treatment, neurons in the grey matter of the cord were affected and vacuolization was observed in the white matter. In animals with paralysis 1 day after treatment, we noticed neuronal degeneration, myelin pallor and sometimes haemorrhagic foci in white and grey matter. As a reaction to the thermal injury, gliosis was observed and invasion of macrophages and lymphocytes (day 3-14). Animals which had severe neurological symptoms at day 1 after hyperthermia, but had recovered completely 28 days after treatment, showed focal scar formation and demyelination in the spinal cord. The observed neurological complications correlated well with the localization of the observed histopathological changes in the cervical spinal cord. PMID- 2921539 TI - Temporal bone venous anomaly of surgical significance. AB - Variability in the size of the dural sinuses and jugular bulb is not uncommon and usually manifests as a high jugular bulb encroaching upon the floor of the middle ear. A rarer entity is the superior and medial extension of the jugular bulb into the bone of the posterior wall of the internal auditory meatus. We report a case where this anomaly was encountered during acoustic neuroma surgery making exposure of the fundus of the internal auditory meatus technically impossible. The possibility of a communication with the superior petrosal sinus is discussed. PMID- 2921540 TI - Aneurysm of the anterior inferior cerebellar artery mimicking an intracanalicular acoustic neuroma. PMID- 2921541 TI - Mycotic aneurysm of the petrous portion of the internal carotid artery. AB - A case of a mycotic aneurysm of the petrous portion of the internal carotid artery is presented. This entity is extremely rare and the problems associated with the diagnosis and clinical management are discussed. PMID- 2921542 TI - Post-traumatic asymptomatic saccular aneurysm of the internal carotid artery. AB - A patient presented with mild upper airway obstruction after being shot from behind through the neck and soft palate. Two days later he developed palsies of the IXth to XIIth cranial nerves inclusive on the traumatised side. These palsies resolved spontaneously after three weeks. Further investigation revealed the presence of a saccular aneurysm of the internal carotid artery. The internal carotid artery was ligated after gradual closure for three days using a Preston clamp. PMID- 2921543 TI - Recurrent bilateral peripheral facial palsy. AB - Facial nerve paralysis is a common otolaryngological diagnosis. Recurrent unilateral peripheral facial palsy is found in about 7 per cent of the cases. Simultaneous bilateral facial palsy is relatively uncommon and occurs in 0.3-2.0 per cent of cases of facial palsy. Recurrent, simultaneous, bilateral, idiopathic facial palsy to the best of our knowledge has never been reported. A case of recurrent, simultaneous, bilateral, idiopathic facial palsy is presented. No evidence of systemic or local disease was found in both attacks of peripheral facial palsies. The association with states of stress is the only common finding between the two attacks. PMID- 2921544 TI - Genetic counselling for isolated hearing loss. AB - An investigation into the causes of sensorineural hearing loss in young children has been used as a basis for determining risk factors for parents of children with a hearing loss of unknown origin having a further affected child and for the defect to be passed on to a subsequent generation. The degree of hearing loss likely to be found if further children are affected, is examined. PMID- 2921545 TI - Lasers: importance of power density. PMID- 2921546 TI - Lighting: aid to pharyngeal pouch identification. PMID- 2921547 TI - Organogenesis of the middle ear structures. PMID- 2921548 TI - Does severe water deprivation affect the inner ear? An experimental study of the gerbilline endolymphatic sac. AB - Through an ultrastructural study of the endolymphatic duct (ED) and sac (ES) system, the effects of an impaired body fluid metabolism on the inner ear fluid environment in the mongolian gerbil has been evaluated. A dehydrative state has been determined depriving of water for both five and twelve days this desert animal, which is known to withstand long periods of water abstinence. The morphological changes of the ED and ES under these circumstances have been compared with those induced by ethacrynic acid intoxication. Although the cochlear partition did not show signs of damage, the ED and ES system seems to be negatively influenced by the dehydrative state and displays a marked imbibition of the subepithelial tissue, which at places shows accumulation of an organic matrix. A regulating role for the antidiuretic hormone on the inner ear fluids of the mongolian gerbil is also proposed and discussed. PMID- 2921549 TI - Mycotic infection of the ear (otomycosis): a prospective study. AB - Otomycosis (fungal infection of the ear) is not uncommon clinical problem encountered in our ENT practice. It makes up to 6 per cent of all patients with symptoms of ear disease seen in the Outpatient Clinic. Of the 193 patients with a clinical diagnosis of otomycosis, 171 cases produced positive fungal isolates. In this study Aspergillus species (niger and fumigatus) have been the most common fungal pathogens. Various aetiopathological factors have been examined in detail, and the available literature reviewed. The results of the treatment by nine antifungal agents currently available in Bahrain have been analysed. PMID- 2921550 TI - Validity of tympanometry in cases of confirmed otosclerosis. AB - The otoadmittence or impedance measurements are common procedures in the diagnosis of middle ear pathologies. The present study was undertaken for the purpose of studying the clinical validity of static admittance values in 42 confirmed otosclerotic ears. For both 220 Hz and 660 Hz probe tones only one third of the otosclrotic ears had low admittance values, as expected. The remainder showed admittance values in the normal or high ranges. No significant correlation was found between air bone gap (ABG) and the admittance values. PMID- 2921551 TI - Repair of tympanic membrane perforations using hyaluronic acid: an alternative to myringoplasty. AB - Fifteen dry, small or medium-sized tympanic membrane perforations were treated by local application of 1 per cent hyaluronic acid after excision of the perforation rim. The duration of the perforations ranged from two months to ten years. Fourteen of the perforations were covered within 15 +/- 7.4 (S.D.) days and 5 +/- 2.4 (S.D.) applications were needed to achieve closure. Hyaluronic acid treatment of dry tympanic membrane perforations not exceeding one quadrant seems to be an alternative to surgical myringoplasty. PMID- 2921552 TI - Bone pate repair of the eroded incus. AB - The authors report on a series of 25 patients who, in the process of undergoing tympanoplasty, were noted to have erosion of the long process of the incus. This was repaired with bone pate in an attempt to restore ossicular continuity. The methods and results are presented and the prospects for the future are discussed. PMID- 2921553 TI - Obliteration of the middle ear cleft. AB - All patients who have undergone obliteration of the middle ear cleft at Plymouth are reviewed. All had chronically discharging mastoid cavities and middle ears resistant to medical treatment, and all had at least one major operation to eradicate disease. All had an average hearing loss on the affected side of more than 80 decibels prior to operation. All ears have remained dry since obliteration, with a blind pit in the meatus. There have been no complications apart from a collection of fluid under one muscle flap. PMID- 2921554 TI - Role of post-operative electroneuronography in predicting facial nerve recovery after acoustic neuroma removal: a pilot study. AB - Complete clinical facial paralysis immediately after acoustic neuroma removal occurs in between 40 to 90 per cent of patients despite the fact that the facial nerve has been preserved anatomically. Some of these patients improve rapidly with adequate cosmetic and functional recovery. Others however, have incomplete or no return of useful function. A pilot study to assess the prognostic value of electroneuronography (ENOG) in 14 patients following acoustic neuroma removal was performed. The results suggest that post operative ENOG is of value in dividing those patients with anatomically intact facial nerves yet complete clinical paralysis post-operatively into groups: one with rapid improvement to an acceptable functional and cosmetic result and one with prolonged paralysis with incomplete or no recovery. Electroneuronography may thus be used to predict the initial recovery profile in patients with complete facial paralysis after surgery. PMID- 2921555 TI - Evaluation of recent experience in hypoglossal-facial nerve anastomosis in the treatment of facial palsy. AB - This evaluation of recent experience of hypoglossal-facial nerve anastomosis in ten patients who had undergone acoustic neuroma resection, indicates that this procedure may have a role to play in the treatment of this disfiguring condition. Facial symmetry at rest is satisfactory in the majority of patients, who suffered little long term deficit from the loss of their hypoglossal nerve. This procedure is ideally suited to otolaryngological practice. PMID- 2921556 TI - Effect of respiration on nasopharyngeal radiographs when assessing adenoidal enlargement. AB - Clinical assessment of adenoidal enlargement in children is difficult and so the lateral nasopharyngeal radiograph is frequently used to assess both adenoid size and the appearance of the adjacent airways. Various measurements of the soft tissues and airways can be made to assess normality or otherwise. Little previously has been mentioned about the physiological conditions, particularly the mode of respiration, under which these radiographs should be obtained and how changes in these conditions affect their appearance. The marked effect in the appearances of nasopharyngeal soft tissues and palatal airway on simply changing from mouth to nose breathing is presented, and an alternative method of examination, for use under certain circumstances is described. PMID- 2921557 TI - Cholesteatoma of the external auditory canal in hemifacial hypertrophy (hyperplasia). AB - Congenital hemifacial hypertrophy is an extremely rare condition. At the time of writing this article, there have been 37 cases reported in the literature. Of these, only two have appeared in the otolaryngologic literature. Cholesteatoma of the external auditory canal (EAC) in hemifacial hypertrophy has not been reported before. This article reports one such case, and discusses the classification of hemihypertrophies. A review of the literature is included in the discussion. Management of cholesteatomas of the external auditory canal is also touched upon. A new theory for the peculiar site selection of cholesteatomas of the external auditory canal is postulated. PMID- 2921558 TI - Morphology of a columellaform stapes. AB - A columellaform stapes found in male patient 18 years old with a conductive hearing loss, has been examined by SEM and light microscopy. The ossicle was smaller than a normal stapes. The head was linked to the base by a crural plate, probably formed by the fusion of the material of the two crura. Microscopy showed a slightly less interwoven structure of the fibrillar bone present mainly at the cranial aspect of the crural plate. Honeycomb-like bone was confined to the caudal part of the crural plate. Microscopy revealed a cavity in the centre of the stapes at the transition between the base and the plate. During surgery, a bony structure was found linking the posterior side of the head of the stapes to the pyramidal eminence. Post-operative audiograms revealed improved hearing with some residual conductive loss of about 10 dB. This case illustrates that a columellaform stapes may occur without forming part of a syndrome. PMID- 2921559 TI - Localized middle ear effusions: three unusual acute cases in adults. AB - Three cases of acute, non-suppurative otitis media in adults are described. They are unusual in that the effusion was confined to the upper middle ear, whilst the lower middle ear was aerated. The aetiology of such localized effusions, is probably related to the anatomy of the middle ear compartments, the mucosal folds forming them and the apertures allowing communication between them. The compartments are relatively constant and are a result of the embryological development of the middle ear. The localization of these effusions, demonstrates the segmental anatomy of the middle ear. PMID- 2921560 TI - Carcinoid tumour of the middle ear. AB - Carcinoid tumours belong to the rarer neoplasms of the middle ear. In 1980, Murphy et al. described the first case of a carcinoid tumour of the middle ear. Only five cases could be traced in the literature. The light and electron microscope features of a primary atypical carcinoid tumour of the middle ear are presented and compared with those described in the literature. Primary carcinoid of the middle ear appears to be derived from the epithelial lining of the middle ear. Distant metastases have not been reported. The duration and nature of the symptoms are of little diagnostic value. An atypical carcinoid tumour in the left ear of a 33-year-old woman is described. PMID- 2921561 TI - Primary cholesteatoma of the mastoid presenting as cervical abscess. AB - Primary cholesteatoma has been described in a number of sites within the temporal bone. We report an unusual case of primary cholesteatoma, confined to the mastoid, presenting with Bezold's abscess of the anterior cervical triangle, in an otherwise asymptomatic elderly man with normal hearing. PMID- 2921562 TI - Transpalatal approach to the petrous apex. AB - A case is described in which a transpalatal, transpharyngeal approach was used for access to a cyst of the petrous apex. Although its indications are limited, in selected patients this conservative procedure has advantages over the more invasive lateral routes. PMID- 2921563 TI - Traumatic CSF fistula presenting late as a middle ear effusion. AB - CSF otorrhoea is not uncommon following head injury but late presentation is rare. In the case described an unsuspected temporal bone fracture presented after an interval of ten years with a conductive deafness due to fluid in the middle ear simulating serous otitis media. PMID- 2921564 TI - Recurrent meningitis associated with meningioma of the mastoid cavity. AB - A 53-year-old female patient who presented with recurrent meningitis as a result of a meningioma, is reported. The meningioma was found to be wholly contained within the left mastoid antrium. To our knowledge this is the first reported case of a meningioma localised to the mastoid antrium. The patient had been assessed in the ENT department on two separate occasions, 17 years and 19 years previously for nebulous symptoms related to the left ear which had cleared spontaneously. Following a second episode of pyogenic meningitis, both of which were associated with aural symptoms, radiological examination suggested an intramastoid pathology which prompted mastoid exploration. Histological examination of the mass confined to the mastoid antum provided the diagnosis of meningioma. There was no clinical or radiological evidence of extratemporal spread of tumour. PMID- 2921565 TI - [Study of the HLA system and glyoxalase in 31 insulin-dependent diabetics free from micro and macro-angiopathies after more than a 20-year development]. AB - Insulin-dependent diabetics are not equal as concerns vascular complications. Many factors have been incriminated. The object of this study was to determine if a genetic factor protected the insulin-dependent diabetic from vascular complications. The population included 31 unrelated, white insulin-dependent diabetic subjects (18 females and 13 males), with diabetes of over 20 years' duration (21 to 43 years, m +/- SD 27.82 +/- 6.03 years; age at diagnosis: 2 to 57 years, m +/- SD 22.7 +/- 15.19 years). The absence of vascular lesions was checked for by the following investigations: visual acuity, fundoscopic examination, retinal fluorescein angiography (Canon F 60 Z), systolic pressure on the thigh and ankle, Doppler velocimetry, plethysmography of the lower limbs, serum creatinine level, urinary protein. The study of the HLA A, B, DR specificities was carried out using the Tersaki microlymphocytotoxicity assay, those of C4 by high voltage gel electrophoresis followed by hemolytic detection, those of B1 using Alper's method and those of glyoxalase by gel electrophoresis followed by a glutathione redox reaction in order to test for a marker for a possible protective genetic factor against complications. The antigen frequencies found were compared with: 1) Those in the general Caucasian reference population (9th Histocompatibility Workshop, 1984). The study group presented the HLA characteristics known to occur in insulin-dependent diabetes: increase in A30, B8, B18, D6, DR3, DR4, BfF1 and decrease in A3, B7, DR2. Furthermore an increase in the frequency of DRw53, DQw2 and DQw3 alleles was noted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2921566 TI - [The influence of anthropometric factors, hemorheologic parameters and the level of arterial pressure on pulse wave velocity]. AB - The measurement of the pulse wave velocity (PWV) is widely used in clinical practice to assess the elasticity of the arterial system. It can be influenced by a number of factors. The present study was undertaken to assess the possible role of anthropometric factors, hemorheological parameters and blood pressure on this element. STUDY DESIGN: Sixty-three male subjects, mean age: 21 +/- 1.6 years,; height: 177 +/- 7 cm; weight: 76 +/- 13 kg, were subjected to Doppler measurement of the carotid-femoral PWV with synchronous recording of blood pressure. In parallel, the following were carried out: nycthemeral blood pressure recording, measurement of plasma vicosity and erythrocyte deformability, determination of hematocrit, fibrinogen and total proteins. The Quetelet indices and body surface area (BSA) were calculated for each patient. These data were analyzed by multiple linear regression. RESULTS: Three parameters affect PWV: 24-hours diastolic blood pressure, hematocrit, and body surface area (the coefficient of multiple correlation: r = 0.597, the percent variability of the explained variable is equal to 35.7%, the regression equation can be written: PWV CF (cm/sec) + 0.283*Diast/24 hours + 0.742* hematocrit + 9.486* BSA = 0.629). The following parameters are not involved: plasma viscosity, erythrometry, total proteins, fibrinogen, Quetelet index, systolic and diastolic blood pressure during the investigation, mean systolic pressure and mean heart rate over 24 hours. COMMENTS: The PWV-diastolic pressure relationship is well-known. In contrast, the effect of the hematocrit and body surface area has never been reported.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2921567 TI - [Study of the veno-arteriolar reflex in young and elderly subjects by recording of TcPO2]. AB - The variations' measurement of transcutaneous oxygen tension (TcPO2) looks as an interesting local vasomotor reflex (L.V.R.) exploration, particularly on lower limbs arterial occlusive disease. However the possible impacts of physiological ageing upon this reflex have not clearly been evaluated. But they can be better analysed with a dynamic measure of TcPO2 on the first intermetatarsal space of the patient, successively recumbent, sitting standing and walking on a moving walkway. TcPO2 is measured with a Radiometer TCM3 oxygen monitor. Two groups of patients, without any arterial occlusive lesion, have been tested like that: 20 young (mean age: 23.3 +/- 1.8 years) and 16 older subjects (mean age: 68.3 +/- 6 years). In recumbent position, TcPO2 is about 74.05 +/- 5.6 mmHg in young and 62.2 +/- 4.7 mmHg in older subjects (P less than 0.01). From recumbent to sitting position, after 15 seconds TcPO2 is elevating to a maximal value at 1 min 30 sec. (85 +/- 6 mmHg in young--71.5 +/- 5 mmHg in older subjects--P less than 0.01). Whilst in young TcPO2 decreases slowly to a stable value, at 5 minutes, higher than in recumbent (+ 6.3 +/- 0.5 mmHg), in the older TcPO2 increases ever to a stable value higher than in recumbent (+ 12 +/- 0.7 mmHg). For the last ones there is no TcPO2 adaptation from recumbent to sitting position because of the vascular ageing, while the LVR increased from recumbent to standing position. During the walk, the LVR disappears for both of them. These measurements confirm the decrease of vascular reactivity with ageing and oblige to compare the results on same age people, during the arterial occlusive disease exploration, by evaluating the graph kinetics. PMID- 2921569 TI - [Therapy of Buerger's disease]. PMID- 2921568 TI - [Etiopathogenesis of Burger's disease]. PMID- 2921570 TI - [Surgical aspects in the therapy of Buerger's disease]. AB - Buerger's disease is generally not improved by reconstructive surgery. This one may be expected to succeed only on the atherosclerotic occlusions which eventually occur. Surgical treatment is therefore essentially based on the lumbar sympathectomy, both for trophic purpose as well as for pain relief. Criteria for unavoidable amputations are then exposed. PMID- 2921571 TI - [Capillaroscopy and diabetic microangiopathies]. AB - Using conjunctival capillaroscopy, the authors studied 40 diabetic patients during glycemic decompensation. The capillaroscopic test, after all metabolic control tests, was repeated 1 and 3 months later and demonstrated improved microcirculation in 10 patients, and proved that therapeutic control is possible during the progression of diabetic microangiopathy. PMID- 2921572 TI - [The value of studying the ocular conjunctiva in case-finding in prediabetic states]. AB - Capillaroscopy, the only method available for the study of the microcirculation, without modifying its hydraulics, often provides a wealth of information in certain systemic diseases in which the microcirculatory involvement precedes clinical manifestations and of course, macrovascular complications. The prospective study of a healthy population is particularly demonstrative and the authors proposed scores on which diabetic microangiopathy could be suspected. The latter was confirmed by detailed laboratory investigations on one hand, and by the course of the disease on the other. For this reason, any subject at risk of diabetes should undergo at least one annual capillaroscopic examination of the ocular conjunctiva or if not, of the peri-ungual region. Furthermore, the study of microvessels in subjects with controlled and treated disease showed a regression of the anomalies which depended on proper control of diabetes, and this particularly nontraumatic test procedure which can be repeated and provides a wealth of information, can give a good reflection of proper therapeutic control, especially if it is performed by a trained and experienced investigator. PMID- 2921573 TI - [The contribution of femoral hemodynamics (velocity, intra-arterial pressure) in the indications for vascular reconstruction in ischemia of the lower limbs]. PMID- 2921574 TI - Normal limits of the electrocardiogram in a Chinese population. AB - 12-lead electrocardiograms (ECGs) from 503 healthy Chinese individuals were computer-analyzed to derive the normal limits of the ECG in a Chinese population. With respect to ECG amplitudes, there were highly significant differences between men and women. The mean S wave amplitude in V2 decreased with increasing age, but the mean R wave amplitude in V5, for example, remained remarkably constant throughout the age groups. The QRS duration was on average 7.6 msec shorter in women than in men. The mean frontal QRS axis shifted superiorly by 17 degrees with increasing age, resulting in an upward trend in R wave amplitude in leads I and aVL. It was concluded that ECG diagnostic criteria for Chinese individuals should be age- and sex-dependent. PMID- 2921575 TI - The QT interval during exercise in healthy children 6-14 years old. AB - Some children and adolescents with stress-induced syncope and a normal QT interval at rest are said to have a prolonged QT interval during exercise. Normal values for the QT interval of children during exercise, however, are lacking. Therefore, the authors determined, in 60 healthy boys aged 6-14 years, the QT interval during stepwise increase in exercise on a bicycle ergometer and constructed a graph containing, with a probability of 95%, at least 90% of normal QT intervals during exercise within its confidence limits. The QT interval as a function of heart rate during exercise can be expressed by the equation QT (s) = 0.4 - 9.18.10(-4) x heart rate (min-1) +/- 0.02. PMID- 2921576 TI - Effect of changes in the definition of ventricular tachycardia on the prevalence of complex ventricular ectopy. AB - The presence of ventricular tachycardia (VT) is commonly considered to represent a risk factor for sudden cardiac death as well as an indication for antiarrhythmic drug therapy. Although spontaneous VT is generally diagnosed by the presence of three or more consecutive ectopic beats, proposed criteria for induced VT require six or more complexes at rates exceeding 90 or 100 beats/min. To determine the clinical implications of a similar change in the diagnostic criteria for spontaneous VT, the authors examined 324 consecutive 24-hour ambulatory electrocardiograms. Of these, 111 (34.3%) had episodes of three or more ventricular premature beats. If six or more beats were required, only 34 (30.6%) would have been diagnosed as having VT. Requiring a minimum rate of 90 or 100 beats/min had less consequence, eliminating only 10 (9.0%) and 12 (10.8%) patients, respectively. Patients with only three to five beat runs had significantly fewer isolated premature beats (4,462.8 +/- 588.4 vs 7,158.1 +/- 1,688.1) and ventricular couplets (186.2 +/- 39.2 vs 294.3 +/- 74.4) per day, and slower average rates (142.1 +/- 4.6 vs 171.8 +/- 6.7 beats/min) during ventricular tachycardia than did those with runs of six or more beats. Thus, altering the definition of spontaneous VT has marked effects on the prevalence of this arrhythmia. Those patients excluded did, however, have a lower prevalence of associated electrocardiographic risk factors. PMID- 2921577 TI - Body surface maps of ectopic P waves originating in the left atrium in the dog. AB - Body surface maps of the P wave in dogs stimulated at various sites on the atria were prepared to find diagnostic signs to detect the origin of left atrial rhythm. Body surface electrograms from 87 points on the thorax and 8-12 points on the epicardial surface of both atria were simultaneously recorded. The body surface P maps disclosed characteristic findings according to whether the site of the stimulation was at the lower right atrium (RA) or the upper, middle, or lower left atrium (LA). In the LA rhythm, the maximum of the P maps moves from the left to the right chest during the later phase of atrial excitation, while it goes from the right to the left in the sinus or the RA rhythm. In the P maps of the rhythm originating in the upper LA, the minimum always stays at a position on the chest above the location of the maximum, while the negative potential areas are above the positive ones. The maps of the middle LA rhythm show that the maximum and the minimum are located horizontally to each other on the chest. The positive and negative areas cover both sides of the chest, separated by zero lines running vertically. In the low LA rhythm, the maximum is always located at a position on the chest above the minimum, and the positive areas are above the negative ones. These results indicate that mapping of the body surface P waves is a valuable method for diagnosing left atrial rhythm and for detecting the approximate location of its origin. PMID- 2921578 TI - Electrocardiographic markers of impaired left ventricular ejection performance in aortic stenosis. AB - To determine whether the ECG would be useful in the prediction of impaired left ventricular ejection performance in aortic valve stenosis, the authors evaluated 121 patients according to (1) the time relationship of the R peak in V6 to the S peak in V2; and (2) the negative P wave terminal force in V1 (Morris index, n = 109). Left ventricular ejection fraction (LVEF) was significantly depressed in patients with the R peak in V6 later than the S peak in V2 (R peak delay in V6, n = 24), compared with those with the R peak in V6 preceding the S peak in V2 or with both peaks occurring simultaneously (n = 97) (LVEF 40.8 +/- 11.8% vs 69.9 +/ 13.3%, p = .000). LVEF less than 55% was present in 87.5% of patients with the R peak delay in V6 and in only 23.7% of those without this finding. The Morris Index was significantly greater in patients with LVEF less than 55% (n = 39) than in those with LVEF greater than or equal to 55% (n = 70) (Morris Index 0.063 +/- 0.035 msec vs 0.030 +/- 0.025 msec, p = .000). The R peak delay in V6 is a highly specific (96.1%), but less sensitive (47.7%), indicator of depressed LVEF, its positive predictive value and predictive accuracy being 87.5% and 78.5%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2921579 TI - The effect of torso inhomogeneities on body surface potentials quantified using "tailored" geometry. AB - The effect of torso inhomogeneities on the electrocardiographic body surface potentials in general, and the waveform of the QRS complex in the standard leads in particular, were studied by using an inhomogeneous, numerical model of the torso including the (lower) conductivity of the lungs and the (higher) conductivity of the ventricular cavities. The relevant geometry was derived from actual data as measured from NMR scans of the subjects studied. The simulated potentials were compared to the body surface potentials recorded in the same individuals. In view of the observed high quality of the correspondence in the fully inhomogeneous case, the quantitative results of the study of the effects of the involved inhomogeneities attain a high level of credibility. To facilitate this analysis a new tool is introduced: the contribution maps. PMID- 2921580 TI - Compensating conduction times as a mechanism of alternating reentry tachycardia: computer modelling experiments. AB - This article concerns a currently reported hypothesis explaining the alternations of conduction time during intra atrioventricular (AV) nodal reentrant tachycardia (AVNRT). This hypothesis supposes simple mutual influence of sequences of intranodal conduction during reentry tachycardia that use the same circuit in different tachycardia cycles. It has been suggested that delayed conduction prolongs the recovery time of the circuit, thus making it possible to transmit the excitation wave with a faster speed in the next tachycardia loop; this less delayed loop shortens the recovery interval of the pathway and results in subsequently delayed conduction of the following tachycardia cycle. A computer model simulating intra-AV nodal reentrant conduction was used to imitate and prove this hypotheses. The results are negative, showing that the suggested mechanism is too simplistic and that either the pathophysiologic background of the AVNRT cycle length oscillations must be different or additional phenomena must be considered to improve the hypothesis. PMID- 2921581 TI - Arrhythmogenic effects of mexiletine in infarcted Purkinje tissues. AB - The electrophysiologic effects of mexiletine on canine subendocardial Purkinje's fibers were examined 24 hours after a two-stage ligation of the left anterior descending coronary artery. Transmembrane potentials were recorded simultaneously in normal (NZ) and infarcted (IZ) zones before and during superfusion with mexiletine. Mexiletine (3, 6, and 9 mg/l) reduced the values of maximum diastolic potential (MDP), action potential amplitude (APA), and maximum rate of phase 0 depolarization (Vmax). The effective refractory period (ERP) was lengthened by the drug. These findings are consistent with the actions of class IB antiarrhythmic drugs. In 42% of the preparations examined, repetitive responses were induced at or near the ERP during superfusion with 3 mg/l mexiletine. These extra responses were no longer elicited during superfusion with 6 mg/l mexiletine. A mechanism for the origin of these reentrant-type arrhythmias based on the action of mexiletine is presented. PMID- 2921582 TI - Hypocalcemic Torsades de Pointes. AB - Torsades de pointes is a unique form of ventricular tachycardia that occurs in the presence of prolonged QT interval. Many predisposing factors have been identified. A classical form of torsades de pointes occurring in the presence of hypocalcemia and prolonged QT interval in an elderly woman is reported. In this patient the QT prolongation was markedly rate-dependent. Hypocalcemia was a postoperative complication following removal of parathyroid adenoma, performed earlier for hyperparathyroidism. Torsades de pointes did not recur after normalization of serum calcium. To the authors' knowledge, this is the first electrocardiographic documentation of hypocalcemic torsades de pointes. PMID- 2921583 TI - Hyperkalemia-like ECG changes simulating acute myocardial infarction in a patient with hypokalemia undergoing potassium replacement. AB - A pseudo-infarctional ECG pattern, previously noted to occur rarely in association with hyperkalemia, was observed in a patient with severe hypokalemia in the course of K+ replacement but while she was still hypokalemic. It is inferred that this puzzling ECG feature reflected a reduction of intracellular/extracellular [K+] ratio in a patient with decreased intracellular K+ concentration undergoing rapid K+ repletion. PMID- 2921584 TI - Response-reinforcer contingency and spatially defined operants: testing an invariance property of phi. AB - A chamber containing 72 response keys defining the circumference of a circle 1 m in diameter was used to examine the relation between differentiation of response location and a measure of response-reinforcer contingency known as the phi coefficient. A different target key was specified in each successive phase, and response location was differentiated with respect to the target. Criterional and noncriterional responses (i.e., responses "near" and "far" from the target) were defined using targeted percentile schedules to control the overall probability of each response class. By manipulating criterional (and, hence, noncriterional) response probability and the reinforcement probabilities conditional on each, a mathematical invariance property peculiar to phi in contingency analysis was examined. Specifically, diagonally interchanging cell frequencies in a 2 x 2 table relating criterional/noncriterional responses to reinforcement/nonreinforcement leaves phi unchanged. Hence, the degree of response differentiation predicted by phi remains unchanged under the four permutations implied by the various diagonal interchanges. This predicted invariance was examined under values of phi equal to .33, .58, and .82. Increasing phi generally increased the stereotypy of response location. Three of the permutations generated almost interchangeable performance at different phi values. The remaining permutation, however, generated functions relating response concentration to phi with slopes shallower than those obtained under the other permutations. This resulted from relatively higher levels of differentiation, compared to the other permutations, at low phi values. These data strongly suggest boundary conditions on the ability of phi to reflect completely the local processes that are indexed by phi at a molar level. PMID- 2921585 TI - The application of Herrnstein's law of effect to disruptive and on-task behavior of a retarded adolescent girl. AB - The purpose of the present study was to evaluate Herrnstein's law of effect as a description of socially significant behavior in an applied setting. The subject was an 18-year-old retarded girl with a history of autistic-like and aggressive behavior. Using a baseline design for two response classes and stimulus conditions, eight categories of subject and staff behavior were monitored over a 3-week period. A computerized observation system, developed for use in the present investigation, was used to obtain real-time durations of the behavior categories alone and in combination. Overlapping durations of teacher and subject behavior were then correlated to yield approximations to a functional definition of reinforcement. Plots of behavior by contingent reinforcement revealed a hyperbolic relationship for each response class, the shape of which varied as a function of extraneous reinforcement r0. In addition, estimated parameters in Herrnstein's equation did not differ significantly from those obtained through independent observation. Finally, Herrnstein's equation accounted for an average 63% of variance in response allocation. Results are discussed in terms of the relevance of matching-law theory to behavior in applied settings. PMID- 2921586 TI - Contextual control of emergent equivalence relations. AB - Three college students in Experiment 1 and 1 student in Experiment 2 learned visual conditional discriminations under contextual control by tones; the visual comparison stimulus that was correct with a given sample stimulus depended on whether a high tone or a low tone was present. Two of the subjects in Experiment 1 then demonstrated the emergence of two sets of contextually controlled three member classes of equivalent stimuli, and the subject in Experiment 2 showed the emergence of contextually controlled four-member classes; the class membership of each stimulus varied as a function of the tones. Class membership was demonstrated by the subjects' performance of new conditional discriminations that they had never been taught directly. In Experiment 2, the procedures were intended to ensure that the tones exerted second-order conditional control and did not simply form compounds with each of the visual stimuli, but the subject's verbal description of the tasks suggested that this intention might not have been successful. It could not be ascertained, therefore, whether the tones exerted contextual control as independent second-order conditional stimuli or simply as common elements of auditory-visual stimulus compounds. PMID- 2921587 TI - Children's identity matching and oddity: assessing control by specific and general sample-comparison relations. AB - After children in Experiments 1 and 2 learned identity matching or oddity, control by sample-comparison relations was assessed. Tests for generalized control displayed novel samples and two comparison stimuli, one identical to the sample. Specific relations were tested with identical or nonidentical sample comparison stimuli from one set of stimuli and substitute comparisons from either the other training set or from a novel set. When tests displayed identical stimuli, patterns of comparison selection suggested control by generalized identity and oddity. However, selection patterns varied when stimuli were nonidentical and familiar or novel substitute comparisons were used. Therefore, control by specific relations is not a precondition for generalized identity and oddity. One set of training stimuli was used in Experiment 3, and generalized performances occurred again. Moreover, control by specific relations was shown by the oddity subjects and 2 of 6 identity subjects. Generalized and specific control may therefore exist simultaneously. In Experiment 4, selections were irregular on tests displaying substitute comparisons and samples and familiar comparison stimuli; this finding supported the relational account of specific sample-comparison control found in Experiment 3. PMID- 2921589 TI - Stimulus class formation and stimulus-reinforcer relations. AB - This study examined stimulus class membership established via stimulus-reinforcer relations. Mentally retarded subjects learned conditional discriminations with four two-member sets of visual stimuli (A, B, C, and D). On arbitrary-matching trials, they selected comparison stimuli B1 and B2 conditionally upon samples A1 and A2, respectively, and C1 and C2 conditionally upon B1 and B2, respectively. On identity-matching trials, they selected all stimuli as comparisons conditionally upon identical stimuli as samples. Throughout training, correct selections of A1, B1, C1, and D1 were followed by one reinforcer, R1, and those of A2, B2, C2, and D2 were followed by another, R2. Subsequent tests documented the formation of two four-member stimulus classes, A1-B1-C1-D1 and A2-B2-C2-D2. The class membership of the A, B, and C stimuli could have been based on equivalence relations that resulted from the arbitrary-matching training. D1 and D2 had never appeared on arbitrary-matching trials, however. Their class membership must have been based on relations with R1 and R2, respectively. Results thus confirm a previous finding that stimulus classes can be expanded via stimulus-reinforcer relations. They also define more precisely the potential nature of those classes and the conditions under which class membership can be established. PMID- 2921588 TI - Effects of atropine on the repeated acquisition and performance of response sequences in humans. AB - The present study assessed a 24-hr time course for the acute effects of intramuscular injections of atropine sulfate (0, 1.5, 3.0, and 6.0 mg/70 kg) in healthy adult humans responding under a two-component multiple schedule of repeated acquisition and performance of response sequences. Subjects resided in an inpatient research ward for the duration of the study. In each component of the multiple schedule, subjects completed a different sequence of 10 responses in a predetermined order using three keys of a numeric keypad. In the acquisition component, the subjects' task was to acquire a new sequence each session. Eight sessions were conducted daily: one immediately before administration of the drug and then 0.5, 1.5, 3.0, 5.0, 7.0, 9.0, and 24.0 hr after administration. In the performance component, the response sequence always remained the same. Overall percentage of errors increased and overall response rates decreased in the acquisition and performance components as an orderly function of drug dose. However, these effects were selective in that behavior in the acquisition component generally was affected at lower doses than in the performance component. When behavior was affected in both the acquisition and performance components, the time courses of effects were similar. Drug effects began at 0.5 or 1.5 hr, reached peak effects between 3.0 and 5.0 hr, and returned to placebo levels between 7.0 and 9.0 hr postdrug in both schedule components. None of the drug doses produced reliable effects the day after drug administration (24-hr postdrug) in either schedule component. The present study provides the first within-subject assessment of the magnitude and duration of the effects of an anticholinergic on repeated acquisition and performance baselines and extends to atropine the selective effects on these two baselines demonstrated previously with other compounds in humans and nonhumans. PMID- 2921590 TI - Theories of probabilistic reinforcement. AB - In three experiments, pigeons chose between two alternatives that differed in the probability of reinforcement and the delay to reinforcement. A peck at a red key led to a delay of 5 s and then a possible reinforcer. A peck at a green key led to an adjusting delay and then a certain reinforcer. This delay was adjusted over trials so as to estimate an indifference point, or a duration at which the two alternatives were chosen about equally often. In Experiments 1 and 2, the intertrial interval was varied across conditions, and these variations had no systematic effects on choice. In Experiment 3, the stimuli that followed a choice of the red key differed across conditions. In some conditions, a red houselight was presented for 5 s after each choice of the red key. In other conditions, the red houselight was present on reinforced trials but not on nonreinforced trials. Subjects exhibited greater preference for the red key in the latter case. The results were used to evaluate four different theories of probabilistic reinforcement. The results were most consistent with the view that the value or effectiveness of a probabilistic reinforcer is determined by the total time per reinforcer spent in the presence of stimuli associated with the probabilistic alternative. According to this view, probabilistic reinforcers are analogous to reinforcers that are delivered after variable delays. PMID- 2921591 TI - M-mode echocardiographic findings in apparently healthy, non-athletic Norwegians aged 20-70 years. Influence of age, sex and body surface area. AB - In order to assess M-mode echocardiographic recordings in a normal Norwegian population, 190 apparently healthy subjects (95 women and 95 men) aged 21-69 years were examined with an Irex Meridian system. Measurements were performed according to criteria recommended by the American Society of Echocardiography. Absolute values for all parameters except for left ventricular (LV) shortening fraction (SF) were greater in men (P less than 0.001). When corrected for body surface area (BSA), the differences between the two genders were far less pronounced. Women had greater left atrium (LA) (P less than 0.01) and LV end diastolic diameter (EDD) (P less than 0.001), whereas the interventricular septum in end-diastole (IVS-ED) (P less than 0.05) and LV posterior wall (PW) in ED (P less than 0.001) were thicker in men. Only weak correlations between age and the various echocardiographic parameters with r-values less than or equal to 0.30 were observed. It is recommended that BSA corrected values should be preferred since the differences between men and women are negligible. When absolute values are used, different normal ranges for both sexes should be applied. PMID- 2921592 TI - Computer-detected ventricular tachycardia in the coronary care unit: prognosis in patients with and without acute myocardial infarction. AB - Survival (for up to 6 years) in coronary care unit (CCU) patients with ventricular tachycardia (VT) was studied with the aid of an automated arrhythmia monitoring system. Ventricular tachycardia was defined as four or more consecutive ventricular beats with a rate above 120 per min. During an 18-month period. VT was observed in 102 individuals (13%) out of 800 patients without acute myocardial infarction (AMI). The 102 patients were compared with age- and sex-matched patients with AMI and VT and a group with AMI but without VT. Hospital mortality was 27% in patients with AMI and VT, 23% in patients with AMI without VT, and 16% in non-AMI patients with VT (NS). First year mortality after discharge was 20% in the non-AMI group compared to 12% in the AMI groups (NS). The 1-6 years survival curves also did not differ significantly between the groups with a yearly mortality of between 5 and 6%. Acute myocardial infarction patients with rapid VT (greater than 150 min-1) or long VT (more than 10 beats) had a higher hospital mortality, otherwise the number or type of VT episodes did not relate to short- or long-term prognosis in the studied groups. Ventricular tachycardia in the CCU did not seem to be an indicator of poor long-term prognosis. It is concluded that long-term prognosis in patients with VT in the CCU was little influenced by a current diagnosis of AMI. PMID- 2921593 TI - Complete occlusion of the left main coronary artery: clinical and angiographic observations in five cases. AB - Involvement of the left main coronary artery is observed in approximately 5 to 8% of patients with coronary artery lesions detected by coronary angiography, but occlusion of the left main artery is a very infrequent finding. Out of approximately 4000 patients undergoing coronary angiography, four men and one woman, 37 to 60 years old, showed total occlusion of this vessel. Four of them had angina pectoris and three had had a myocardial infarction. All five showed deep ST depression in V 2(or 3)-6 during bicycle exercise testing. Apart from the left main artery occlusion, all had significant obstructive lesions in other coronary vessels, including the right coronary artery or its major branches. There was collateral circulation from the right coronary artery in all patients. Left ventricular function was well preserved in three patients and markedly impaired in two. Four patients underwent bypass surgery and they have been followed for 10 to 28 months. Three are free of angina and one has only minimal angina. One patient refused surgery and he continued to have severe angina despite intense medical treatment. He died suddenly after 30 months follow-up. In patients with complete occlusion of the left main coronary artery, development of adequate collateral flow seems important in preserving left ventricular function, but collaterals are usually insufficient to prevent angina. Moreover, associated obstructive lesions in other coronary arteries constitute a potential threat to the collateral circulation. Effective symptomatic relief is obtained by coronary bypass grafting, and revascularization may also improve prognosis in this subset of patients with coronary heart disease. PMID- 2921594 TI - Advanced cardiac life support in the prehospital setting: the Reykjavik experience. AB - Since 1982 a mobile emergency care unit (emergency ambulance) manned by a physician has been operated in Reykjavik. During 1982-1986 there were 138 attempted resuscitations in sudden cardiorespiratory arrest from cardiac causes. Twenty-four patients (17%) were discharged home, all but one without mental impairment. Seventy-three patients presented with ventricular fibrillation, 21 (29%) of which were discharged. The mean ambulance response time was 5 min. Bystanders initiated cardiopulmonary resuscitation (CPR) in 40 cases (29%) which significantly improved the outcome. In witnessed arrests, 19 of 36 patients (53%) with bystander-initiated CPR were discharged compared to 5 of 62 patients (8%) where CPR awaited the arrival of the ambulance team. These results are comparable to those obtained in larger metropolitan areas. In small urban areas the size of Reykjavik (population of 110,000), an advanced and efficient prehospital care can be organized as an extension of the emergency departments role. PMID- 2921595 TI - Haemorrhagic and thromboembolic complications in patients with atrial fibrillation on anticoagulant prophylaxis. AB - We studied clinically relevant haemorrhagic and thromboembolic events in 213 patients with atrial fibrillation (AF) during 818 patient-years of anticoagulant (AC) treatment. The incidence of complicating events per 100 patient-years of treatment in three groups of patients, those with mitral valve disease (MVD; n = 34), without MVD (n = 102) and those with previous thromboembolism (TE; n = 77) was: major peripheral haemorrhages 3.1, 3.3 and 8.2 (non-MVD vs. TE group, P less than 0.05), cerebrovascular events 3.9, 3.0 and 3.0 (NS), and peripheral arterial thromboembolism 0, 0 and 1.5 (non-MVD vs. TE group, P less than 0.05). The proportion of thrombotest values less than 5 and/or greater than 20% at regular check-ups was 9.8% in patients with and 6.9% in patients without major peripheral haemorrhages (P less than 0.01). Major peripheral haemorrhages are frequent in patients with AF receiving AC treatment. They are most likely to occur in those with previous thromboembolism and among those with unstable AC control. PMID- 2921596 TI - Pancytopenia--a rare manifestation of folic acid deficiency. AB - In the western world folic acid deficiency is a relatively rare cause of anaemia in the elderly population. A 79-year-old woman presented with pancytopenia (haemoglobin 3.4 mmol l-1, leucocytes 1.2.10(9)l-1, thrombocytes 22.10(9)l-1) due to folic acid deficiency. The deficiency was caused by an extremely low dietary intake. The case was complicated with infection and haemorrhagic manifestations. Administration of folic acid increased the number of erythrocytes, leucocytes and thrombocytes markedly. Beside vitamin B12 deficiency folic acid deficiency must be borne in mind in megaloblastic anaemias complicated with leucopenia and/or thrombocytopenia. Since the body stores of folic acid are low, rapid diagnosis and treatment are important. PMID- 2921597 TI - Hyposelenaemia: patients with gastrointestinal diseases are at risk. AB - A retrospective study of serum selenium determinations performed in a hospital laboratory revealed 47 cases of hyposelenaemia (defined as a serum selenium level below 0.74 mumol l-1). Moderate hyposelenaemia (serum selenium 0.30-0.55 mumol l 1) was found in 11 patients and seven of these suffered from gastrointestinal diseases. Furthermore severe hyposelenaemia (serum selenium below 0.30 mumol l-1) was detected in three patients, who were all affected by gastrointestinal disease. We concluded that patients with gastrointestinal diseases are especially at risk of developing selenium deficiency and should be monitored by repeated determinations of serum selenium. Patients with moderate or severe hyposelenaemia should receive selenium treatment. PMID- 2921598 TI - Increased skeletal muscle Na/K-ratio in obese men, but not in women, with glucose intolerance. AB - Obesity is associated with glucose intolerance. Glucose is to a large extent disposed in the skeletal muscle. Peripheral insulin resistance, as well as decreased enzymatic activity in the skeletal muscle, has been suggested in type II diabetes. Potassium is essential for such enzymatic reactions. In this study, obese men, but not women, with glucose intolerance tended to have a lower total body potassium per kg body weight, indicating a smaller muscle mass, than weight matched normoglycaemic men. They also had a lower skeletal muscle potassium content per 100 g dry weight (P less than 0.05) and a higher muscle Na/K-ratio (P less than 0.05) compared with obese men with normal glucose tolerance. Muscle fat and muscle sodium content were higher in obese men than in women with the same body mass index (P less than 0.01). The muscle electrolyte changes can be explained by a decrease in the insulin mediated Na/k-pump activity across the cell membrane or a smaller number of insulin receptors on the skeletal muscle cell in patients with glucose intolerance. PMID- 2921599 TI - The size of the hepatitis delta agent. AB - The size of the hepatitis delta virus was determined by filtration of infectious plasma through polycarbonate membranes and the inoculation of filtrates into chimpanzees. Chimpanzees inoculated with filtrates of 50 nm and 30 nm, but not 15 nm filters, developed delta hepatitis. The minimum size of infectious hepatitis delta virus was estimated to be approximately 30 nm, which is consistent with measurements of particles thought to be the virus. PMID- 2921600 TI - Differential effect of amantadine hydrochloride on the systemic and local immune response to influenza A. AB - Anti-influenza serum and nasal antibody titers were followed during a double blind, placebo-controlled, randomized study assessing the prophylactic efficacy of 50, 100, and 200 mg/day of amantadine hydrochloride against experimental challenge with influenza A/Beth/1/85. The geometric mean titers (GMT) of serum hemagglutination inhibition antibody (P = .05) as well as serum influenza specific IgG (P = .004) were significantly lower for all amantadine groups when compared to placebo. There were no significant differences in the GMT of either type of serum antibody titer comparing any of the three amantadine groups. Viral titers were also lower in the amantadine groups compared to the placebo group and not significantly different among the three amantadine groups. Nasal antibody titers in the 100-mg and 200-mg amantadine groups were significantly lower than placebo titers (P = .002). Nasal antibody titers in the 50-mg amantadine group did not differ significantly from titers in the placebo group (P = .892). Possible reasons for the differential effect of amantadine on the serum and nasal antibody response are discussed. PMID- 2921602 TI - Lymphocyte subsets alteration in patients with argentine hemorrhagic fever. AB - Peripheral blood lymphocyte subpopulations were studied in 15 patients with Argentine Hemorrhagic Fever (AHF), during the acute period of the disease and in early convalescence. Anti-human Ig antibodies were used to identify B cells and monoclonal antibodies to assess T4 and T8 subsets. During the acute period of the disease, significant alterations were found in B, T4, and T8 lymphocytes (P less than .001), as well as in T4/T8 ratios (P less than .001). These abnormalities disappeared in early convalescence, around 30 days after the clinical onset. Diminished numbers of T4 lymphocytes are interpreted as relevant to the immunodepression that characterizes the acute phase of AHF. PMID- 2921601 TI - Female to male transmission of hepatitis B virus between Chinese spouses. AB - Three hundred thirty-seven community-based spouses were tested for the presence of hepatitis B virus (HBV) markers to assess the direction of HBV transmission between couples. The prevalence rate of HBV infection among husbands whose wives were hepatitis B surface antigen (HBsAg)-positive was higher compared with those whose wives were HBsAg-negative. Moreover, the frequency of HBV seropositivity among husbands was 100% if their wives carried HBeAg and showed a trend correlation (P = .009). The prevalence difference was 13.8%, and the 95% confidence interval (95% Cl) was 7.9-19.7% after adjusting for spouses' age. In contrast, HBV infection rate of wives did not show an association with the husbands' HBsAg or HBeAg carrier status. The prevalence difference was 7.1%, but 95% Cl was -2.5-16.8% after adjusting for spouses' age. Female to male transmission of HBV between spouses appears to be more efficient. PMID- 2921603 TI - Shedding of coronavirus-like particles by children in Lesotho. AB - Stools from 266 children in four districts of Lesotho were examined for viruses by electron microscopy (EM) over a 5-week period. Eighty one (30.5%) of the children shed coronavirus-like particles (CVLPs). Shedding was not significantly associated with diarrhea. The proportion of children shedding these particles increased with increasing age. In one district, the prevalence of CVLP shedding (67.9%) was at least twice the prevalence in any of the other three districts. This was the only district to be sampled during the first week of the study. It was shown that the proportion of children shedding CVLPs declined during each of the 5 weeks of study. The stools of six children who shed CVLPs in the early summer of 1984-85 were negative by EM 5 months later. There was no association between the shedding of pathogenic bacteria or parasites and the presence or absence of CVLPs in the stool. PMID- 2921604 TI - Emergence of large plaque-producing clones of human immunodeficiency virus (HIV) in vitro. AB - Large plaque-inducing clones were obtained from small plaque-inducing parental clones of human immunodeficiency virus (HIV) by the plaque-cloning method. The cloned HIVs that formed large and small plaques were studied as follows: 1) infectivity was determined by the ratio of plaque-forming units (PFU) to reverse transcriptase (RT) activity; 2) viral growth was assessed by the amount (RT activity) of virus after infection; and 3) HIV long terminal repeat (LTR)-linked gene expression of the viruses was measured by chloramphenicol acetyltransferase (CAT) assay using persistently infected MOLT-4 cells. Results showed that clones producing large plaques showed similar or slightly lower infectivity but higher virus production, faster viral growth, and higher gene expression activity than clones producing small plaques. These analyses revealed that clones producing large plaques could replicate more rapidly than those producing small plaques. Restriction enzyme map analysis of these cloned viruses showed that they were also genetically different. These results suggest that the changes in the biological features observed here might be due to mutation during the cloning procedure. PMID- 2921605 TI - Epidemiology of molluscum contagiosum using genetic analysis of the viral DNA. AB - The molecular epidemiology of molluscum contagiosum virus (MCV) infections was investigated by restriction endonuclease analysis of the genomes of 222 separate isolates collected from 147 patients living in Germany (33 patients), Hong Kong (6 patients), and Scotland (108 patients). MCV type 1 (MCV-1) caused 96.6% of the infections, and MCV type 2 (MCV-2) caused 3.4%. However, isolates from four of the 142 MCV-1-infected patients and two of the five MCV-2-infected patients showed minor differences in their DNA restriction patterns because of the loss of a single or very few recognition sites for the enzymes used. No genome variations were detected amongst isolates collected from different sites or on several occasions from individual patients or from closely related patients. Southern blot hybridization revealed a high level of relatedness between MCV-1 and 2. No differences were seen in the appearance or anatomical localization of lesions caused by either virus type. In particular, there was no preferred genital localization for MCV-2 infections. PMID- 2921606 TI - Inhibitor of protein synthesis blocks long-term behavioral sensitization in the isolated gill-withdrawal reflex of Aplysia. AB - To study the effects of protein synthesis inhibition on long-term sensitization of the gill- and siphon-withdrawal reflex of Aplysia, we have developed an isolated reflex preparation in which we could expose the inhibitor to only that part of the central nervous system involved in mediating the reflex and not to the other parts of the animal's central nervous system, thus minimizing the possible systemic side effects. We have found that long-term sensitization can be obtained in the isolated gill reflex, and that this long-term process, but not the short-term process, is blocked selectively by anisomycin, a reversible inhibitor of protein synthesis. Moreover, to obtain this blockade of long-term sensitization, this drug need only be applied during the training procedure. PMID- 2921607 TI - A quantitative analysis of the development of the central nervous system in juvenile Aplysia californica. AB - The marine mollusc Aplysia californica has proved to be a useful preparation for analyzing the development of learning and memory on both behavioral and cellular levels. An important issue in this analysis concerns the anatomical substrate upon which learning is superimposed during development. As a first step in examining this question, in the present study we have determined the number of neurons in all the major central ganglia at each stage during juvenile development, a time when several forms of learning first emerge in Aplysia. We found that a large and highly nonlinear proliferation of neurons occurs during juvenile development, with the greatest increase in cell number occurring during a specific juvenile stage: Stage 12. The neuronal proliferation is system-wide, occurring in each of the central ganglia simultaneously, suggesting the action of a general developmental signal or trigger (perhaps a hormone). Accompanying the increase in neuron number in Stage 12 there is a large increase in neuropilar volume (150-fold), which significantly increases the opportunity for synaptic interactions late in juvenile development. PMID- 2921608 TI - Phase I study of the combination of alpha-2 interferon and cisplatinum. AB - Based on preclinical evidence of synergy, we performed a Phase I study of the combination of alpha-2 interferon and cisplatinum in patients with advanced malignancy. A fixed dose of 5 x 10(6) U/m2 alpha interferon was given three times weekly. Cisplatinum was given once weekly at dose levels of 5, 10, 20, 25, and 30 mg/m2. Dose-limiting toxicity consisted of flu-like symptoms and malaise leading to decreased performance status. Response was seen in a patient with metastatic melanoma. Recommended doses for Phase II study are 5 x 10(6) U/m2 of alpha-2 interferon three times weekly and 25 mg/m2 of cisplatinum once weekly. PMID- 2921609 TI - Melanoma patient antibody responses to melanoma tumor-associated antigens defined by murine monoclonal antibodies. AB - Sera from melanoma patients undergoing immunization with three distinct immunogens were evaluated for development of IgG antibody specific for the melanoma tumor-associated antigens (TAAs) GD3 and 250-kd glycoprotein (high molecular weight; HMW). Of 99 patients receiving either irradiated allogeneic melanoma cells admixed with bacillus Calmette-Guerin, vaccinia viral oncolysate melanoma cell membranes, or cholesterol hemisuccinate-modified melanoma cells, 12 were determined to have responded against GD3 and 17 against the HMW TAA. This reactivity was measured using both direct binding to purified TAA and specific inhibition of binding of murine monoclonal antibodies R24 and Me-1-14 for GD3 and HMW TAA, respectively. Preimmune sera from these patients did not react with these TAAs, nor did preimmune sera or follow-up sera from melanoma patients electing not to receive immunotherapy. These results suggest that melanoma patients can be immunized against these TAAs as presented on the melanoma cell membrane in an immunotherapy setting and that immunization using purified TAAs might likewise be feasible. PMID- 2921610 TI - Effects of coumarin (1,2-benzopyrone) and cimetidine on peripheral blood lymphocytes, natural killer cells, and monocytes in patients with advanced malignancies. AB - The combination of coumarin and cimetidine has yielded objective tumor regressions in patients with metastatic renal cell carcinoma and malignant melanoma. While the mechanism of action of cimetidine appears to be immunomodulatory, coumarin appears to have direct effects on tumor cells as well as immunomodulatory activity. We utilized monoclonal antibody labeling techniques to monitor peripheral blood lymphocyte, natural killer (NK) cell, and monocyte phenotypes in patients treated with coumarin and cimetidine. Patients received coumarin 100 mg orally daily for 14 days; on day 15 cimetidine 300 mg four times daily was added and both drugs were continued until disease progression. Studies were performed pre treatment and at 2, 4, and 8 weeks on therapy. There were no alterations in T-cells, helper/inducer T-cells, cytotoxic/suppressor T-cells, B cells, Ia + lymphocytes, or NK cells. However, an increase was noted by 2 weeks on therapy in the percentage of monocytes and the percentage of DR+ monocytes. This change in the monocyte population occurred in the presence of coumarin alone, before the institution of cimetidine. While this treatment appears to increase DR expression by monocytes, further studies with larger numbers of patients are needed to determine if this observed change is related to antitumor response. PMID- 2921611 TI - Effects of coumarin (1,2-benzopyrone) on lymphocyte, natural killer cell, and monocyte functions in vitro. AB - We have demonstrated in a pilot study that the combination of coumarin (1,2 benzopyrone) and cimetidine is capable of producing objective antitumor responses in patients with advanced renal cell carcinoma. In a previous study, we used monoclonal antibody labeling techniques to monitor peripheral blood lymphocytes and monocytes in patients with advanced malignancies treated with coumarin and cimetidine. While there was no quantitative alteration in T-lymphocytes, B lymphocytes, natural killer (NK) cells, or cells bearing Ia antigen, there was an increase in the percentage of CD-14 (M5E2+) monocytes and DR+ monocytes by 2 weeks on therapy that persisted over the 8 weeks of monitoring. Because patients received coumarin for 2 weeks prior to institution of cimetidine, these changes were attributed to coumarin. In this report, we present the results of in vitro studies designed to determine if coumarin alters the functional properties of normal peripheral blood lymphocytes, NK cells, or monocytes. In a standard NK cytolytic assay, coumarin failed to produce any significant alteration in NK activity against K562, ACHN, or Caki-2 cell lines. Coumarin did produce an augmentation of lymphocyte mitogenic response to phytahemagglutinin but not to concanavalin A or pokeweed mitogen. Coumarin produced a modest suppression of superoxide anion and hydrogen peroxide generation by monocytes but not by macrophages. The effect of coumarin on antigen processing of tetanus toxoid by macrophages was examined using normal donor cells. While an augmentation of antigen processing was noted in some normal donors, this was an inconsistent and inconclusive finding. Further studies are required to define the precise effects of coumarin on immune cell populations from both normal subjects and cancer patients. PMID- 2921612 TI - Morphometric alteration of rat myelinated fibers with aging. AB - The number, size, density and pathologic alterations of myelinated fibers (MF) of ventral and dorsal roots and of peroneal and sural nerves in groups of female Fischer 344 rats at 10, 20, and 30 months of age were evaluated to characterize nerve changes with old age. Except for minimal changes in the peroneal nerve, no statistically significant alteration in number of MF/nerve or in the fascicular area was associated with aging. The unaltered number was misleading since striking changes in MF size distribution, pathologic alterations of fibers and the presence of regeneration clusters suggested age-related degenerative and regenerative events. These changes were most dramatic in the ventral root, where myelin infolding, myelin separation from axon and ballooning, macrophagia and hyperplasia of Schwann cell nuclei were pronounced. Concomitant with these alterations, axonal atrophy (a reduction in caliber of axons relative to myelin spiral length or number of myelin lamellae) was demonstrated in MF of the ventral root in old age. PMID- 2921613 TI - Myelin phagocytosis by peritoneal macrophages in organ cultures of mouse peripheral nerve. A new model for studying myelin phagocytosis in vitro. AB - Organ cultures of degenerating nerve fascicles were exposed to cultured macrophages obtained by peritoneal lavage. Invasion of the nerve fascicle by phagocytes was shown by prelabeling with carbon and with electron microscopy. There was massive active phagocytosis of degenerating myelin sheaths. The invading phagocytic cell population was identified as Fc receptor-positive, Mac-1 positive macrophages by immunocytochemistry. The Schwann cell population persisted without significant myelin phagocytosis. The vitality of the Schwann cell population was shown by subsequent reimplantation of the organ cultures into host animals. The reimplants had retained their ability to remyelinate regenerating axon sprouts. These observations were made in cultures exposed to cytostatic agents. If cytostatic agents were omitted, there was proliferation of endogenous phagocytes in the nerve fascicles without added peritoneal cells. These endogenous phagocytes were identified as proliferating resident monocytes and were positive for the Fc receptor and Mac-1 markers. This model allows studies on how monocytes recognize and digest degenerating myelin apart from surviving Schwann cells. PMID- 2921614 TI - Selective localization by neuroglia of immunoglobulin G in normal mice. AB - Plasma proteins including immunoglobulins have been previously localized in neurons with processes extending outside the blood-brain barrier, but not within glia under normal conditions. Immune modulating functions have been proposed for both microglia and astrocytes in several pathological states. Using immunocytochemistry, we have found that large numbers of neuroglial cells contain immunoglobulin G (IgG) in normal mice of the C57 BL/6 strain. Most IgG-positive cells had both the morphology and distribution of microglia, including a higher density in grey matter, and were frequently found in perivascular or perineuronal locations. The accumulation of IgG does not appear to be by nonselective phagocytosis of extracellular fluid, since serum albumin could not be detected within microglia. There was little overlap in the distribution of cellular processes positive for IgG and those which showed astrocytic markers. Neuronal accumulation of plasma proteins was also seen in a distribution described by previous investigators. The function of this selective accumulation of IgG by normal microglia is unknown, but may reflect a role in the immune response within the central nervous system. PMID- 2921615 TI - Teaching home health aides the use of Life Review. AB - Life Review is presented as a therapeutic nursing intervention for the elderly. This article describes a class on life review for home health aides and shows the ease with which these aides managed life review. The description of this class may serve as a model for inservice educators to teach nurse aides the use of life review. PMID- 2921616 TI - Preceptor program evaluation demonstrates improved orientation. AB - Although the preceptor method of orientation is generally accepted as an effective mechanism for orienting newly employed nurses, very few evaluation studies of preceptor programs have been reported in the literature. This article describes a study designed prior to implementing a preceptor program at the University of Wisconsin Hospital and Clinics in order to measure the outcomes of the program. Data were collected on the satisfaction of orientees, preceptors, other staff nurses, and nurse managers. The preceptor role and preceptor's level of comfort and skill were studied. To quantify the economic impact, both length of orientation and nursing turnover were considered. PMID- 2921617 TI - A comprehensive training program for multidisciplinary treatment plans. AB - A client-oriented treatment plan that will direct and coordinate health care staff, thereby ensuring efficient quality client care, is a worthy goal. After planning, implementing, and evaluating a training program for this purpose, the authors concluded that the key to quality client care and successful implementation of this program lies in proper preparation and administrative support. PMID- 2921618 TI - Continuing learning among registered nurses employed in a community hospital. AB - This study indicated that hospital nurses learn through a variety of modes and that part-time nurses participated less frequently in certain learning activities than full-time nurses. Findings will be used to identify and expand resources for learning in this setting, devise strategies for enhancing participation of nurses in a variety of educational activities, and broaden the perspective of the administration and staff in relation to what constitutes continuing learning among professionals. PMID- 2921619 TI - Management education needs of head nurses. AB - Today's head nurses must be skilled in the art of management in order to meet the needs of patients, unit staff, administrative staff, and the employing organization. More hospitals are recognizing the need to offer basic education programs that assist head nurses to develop necessary knowledge and skills. Based on a study of 41 head nurses, the author discusses findings and recommendations for planning education programs for head nurses. PMID- 2921620 TI - Application of the nursing process to a continuing education course. AB - The nursing process is a fundamental component of curricula in schools of nursing. The nursing process also is adaptable to continuing education offerings provided by a nursing education and research department of an urban, community teaching hospital. This article describes how nurse educators used the nursing process as the basis for development, implementation, and evaluation of an advanced medical-surgical continuing education program. PMID- 2921621 TI - Organizational rites and nursing. PMID- 2921622 TI - Quality assurance in nursing staff development. PMID- 2921623 TI - Retaining graduate nurses: a staff development challenge. AB - The high attrition of graduate nurses in their first nursing positions has a significant and costly impact on Staff Development Departments. Orientation of these new practitioners demands increased use of resources (educators, money, and energy) which in turn decreases the availability of these resources for the career development of the more experienced RN staff. To justify this investment, the new graduate must be retained beyond the first year. Staff development educators are challenged to create and test new strategies to facilitate this retention. This article describes one strategy, support groups, and its effect upon the retention and job satisfaction of graduate nurses during their first year of employment. PMID- 2921624 TI - Implementing differentiated practice: the Sioux Valley Hospital experience. AB - Historically, nurses with different levels of education have been used interchangeably in acute care hospitals. If nursing is going to be viewed as a preferred career choice and acute care hospitals are to retain staff, nurse administrators must provide a nursing practice model that differentiates scope of practice based on education. The authors discuss how they implemented a system of differentiated practice. PMID- 2921625 TI - Stoplight Grid: a color-coded visual system for per diem staff assignment. AB - What is the best way to appropriately assign per diem nursing personnel? The author describes a systematic approach to per diem staff assignment called the Stoplight Grid. The Stoplight Grid correlates staff skills and preferences with unit needs and integrates this data into a color-coded system for staff assignment. PMID- 2921626 TI - Concept of the month: implementing King's Conceptual Framework at the bedside. AB - Acknowledging the use of conceptual frameworks as the future of nursing, administrators are searching for methods to incorporate theory into practice. The challenge is to do this in a way that is meaningful and useful to the nurse at the beside. The authors describe how one directorate, in a 650-bed community hospital, developed a program that enabled nurses to understand and apply Imogene King's systems and concepts to their practice. PMID- 2921627 TI - Practice partnerships: the newest concept in care delivery. AB - The shortage of nurses provides an opportunity to advance clinical reasoning to include deciding exactly which hands-on care activities must be done by the professional nurse and which aspects of care can be provided by a nurse extender. The relationship of the professional nurse and her "extender partner" is a new solution to an old problem...one that has lasting power because it advances professionalism. PMID- 2921628 TI - Enhancing the image of nursing. AB - A Task Force from a Midwestern teaching hospital developed a comprehensive strategy to enhance the image of nursing in both the hospital and the community. Nursing administrators will find the Task Force's process and outcomes useful in addressing the image of nursing in their own institutions. PMID- 2921629 TI - Professional liability insurance. PMID- 2921630 TI - Interinstitutional collaboration for nursing excellence: Part 1, Creating the partnership. AB - A partnership between two unrelated public institutions was formed to enhance the quality of clinical learning for students and staff, promote exemplary care to patients, and foster expansion of nursing research. The critical nucleus of the partnership is the unit-based clinical nurse specialist who performs the multiple functions of professional nursing: practice, education, and research. This two part series describes the collaboration effort. Part 1 focuses on the organizational structure created for the partnership, and part 2 reports the findings of a 15-week pilot study conducted to test the model. PMID- 2921631 TI - Manager impact on retention of hospital staff: Part 1. AB - The impact of middle managers on retention of 71 hospital professionals was examined in this prospective study. Price and Mueller's 1981 model of turnover was expanded to include the leadership characteristics of middle managers. In Part 1, research design, methods, and descriptive results are presented. Data on predictor variables were obtained by two questionnaires comprised of established instruments. Retention data then were collected for 6 months. Part 2 of this series, the impact of the manager and recommendations for improving retention, will be presented in the April issue. PMID- 2921632 TI - Providing equal access for deaf clients. AB - Fifteen years after the passage of a law by the Federal Government, many hospitals are still not providing hearing-impaired patients with equal access to their services in a consistent and effective way. Not only does this create frustrating situations for the patients and hospital staff, but it also puts the hospital in the position of noncompliance with the law. The author describes how one hospital addressed this issue at the level of service provision and found some workable solutions. PMID- 2921633 TI - Comparative costs of a cooperative care program versus hospital inpatient care for gynecology patients. AB - The cost of gynecologic care delivered in a cooperative care (co-op) unit was compared with the cost for similar patients treated in a traditional hospital inpatient unit. No significant differences were found. This finding was in direct contrast to our earlier study of obstetric patients where overall savings were achieved. The authors did, however, find cost savings (approximately $450) for those co-op patients cared for by physicians who were frequent users of the unit. Most of the savings for this group was achieved through a reduction in the cost of routine services, which includes nursing care. If the current nursing shortage leads to an increase in co-op units, nursing administrators need to be aware that potential cost savings may depend on physician familiarity with the co-op concept. A major role of nursing therefore, is to provide information on the benefits of cooperative care both to physicians and to potential patients. PMID- 2921634 TI - Values and vision in chaotic times. AB - Nursing administrators can be more successful in stabilizing the major labor force in the hospital by ensuring that organizational values are explicitly shared, discussed, and visible to those in the nursing department. Standards and expectations that operationalize the values must be developed and implemented. Methods to measure accomplishment of the standards must be quantifiable and measured on an ongoing basis and staff and management must be held accountable for the standards. Finally, reward and recognition systems must flow from attainment of the standards that operationalize organizational values. If any one of the components of the model is missing, organizational values cannot be actualized, employees will not experience the stabilizing effect of understanding the values that drive the organization's decision-making, and resources will not be used maximally to move the organization toward its vision of quality patient care. PMID- 2921635 TI - The crisis in nursing administration education. PMID- 2921636 TI - Interinstitutional collaboration for nursing excellence: Part 2. Testing the model. AB - Two unrelated public institutions formed a partnership to foster excellence in professional nursing. The organizational structure was described in Part 1 (February 1989). This second article reports a 15-week pilot study conducted on seven hospital units to determine the degree to which the clinical nurse specialist can merge the multiple functions of professional nursing: practice, education, and research. PMID- 2921637 TI - Effect of dietary lipid composition on rat liver microsomal phosphatidylcholine synthesis. AB - Effects of dietary lipid on microsomal membrane fatty acid composition and phosphatidylcholine synthesis were examined with respect to the degree of saturation and chain length of dietary fatty acids. Diets containing 20% fat (wt/wt), primarily in the form of coconut oil, beef tallow, or soybean oil were fed to weanling rats for 28 d. All diets were adequate in essential fatty acids. Feeding the coconut oil diet, containing more than 50% saturated medium-chain fatty acids, increased the long-chain omega 3 fatty acid levels and altered the ratio of omega 6 to omega 3 fatty acids in membrane phosphatidylcholine and phosphatidylethanolamine compared to that in animals fed diets containing a saturated tallow or polyunsaturated soybean oil diet. Change in membrane fatty acid composition in response to the coconut oil diet was accompanied by decreased synthesis of phosphatidylcholine via the cytidine diphosphate choline (CDP choline) pathway, and increased synthesis via the phosphatidylethanolamine methyltransferase (PEMT) pathway. An overall decrease in phosphatidylcholine production was reflected in a lower ratio of phosphatidylcholine to phosphatidylethanolamine in the membrane. Modulation of hepatic phosphatidylcholine synthesis during early growth thus appears to be in response to the ratio of long-chain omega 6 fatty acids to omega 3 fatty acids in membrane phospholipid rather than levels of specific fatty acids or the relative degree of saturation of fatty acids in the diet. PMID- 2921638 TI - Dietary fat and cholesterol effects on cholesterol metabolism in CBA/J and C57BR/cdJ mice. AB - The aim of this study was to determine how small differences in dietary fats affect cholesterol metabolism in mice hypo- (CBA/J) and hyperresponsive (C57BR/cdJ) to diet-induced hypercholesterolemia. Six-wk-old male mice were fed either a diet corresponding to the U.S. average gross composition (US74, 40% of total energy as fat, 347 mg cholesterol/1000 Kcal, P/S = 0.24) or a modified-fat diet (30% of total energy as fat, 46 mg cholesterol/1000 Kcal, P/S = 0.91). After 8 wk of feeding, neither strain had developed hypercholesterolemia. CBA/J mice had higher concentrations of serum total and high-density lipoprotein (HDL) cholesterol and a higher esterified-to-free cholesterol ratio than did C57BR/cdJ mice. CBA/J mice maintained a constant serum cholesterol concentration mainly by adjusting the hepatic hydroxymethylglutaryl coenzyme A reductase (HMGR) activity, whereas C57BR/cdJ mice did so by changing the fecal excretion of cholesterol. Compared to the modified-fat diet, the US74 diet caused an increase in the ratio of total to HDL serum cholesterol, liver microsomal free cholesterol, fecal cholesterol and hepatic microsomal cholesterol 7 alpha-hydroxylase activity and a decrease in hepatic microsomal HMGR activity. We conclude that the metabolic responses to small differences in dietary fat are different in CBA/J and C57BR/cdJ mice. PMID- 2921639 TI - Plasma lipids, lipoproteins, and fecal excretion of neutral sterols and bile acids in rats fed various high fat diets or a low fat/high sucrose diet. AB - The effect of feeding various diets on plasma lipids and lipoproteins and on fecal excretion of neutral sterols and bile acids was studied in rats fed for 7 wk diets containing 42% of energy as either coconut oil (CO), sunflower seed oil (SO), fish body oil (FBO), cod liver oil (CLO), or a low fat/high sucrose diet (SU). Triacylglycerols (TG) in whole plasma and VLDL + LDL were lower in rats fed high amounts of polyunsaturated fatty acids (PUFA) than in those fed the CO diet. Plasma HDL2 components in FBO and CLO groups were generally lower than in the other groups. Percentages of liver and heart linoleic and arachidonic acid were higher in the SO group, but lower in groups fed marine oils, than in the CO group. There was a high relative amount of eicosapentaenoic and docosahexaenoic acid in liver and heart of rats fed marine oils. Fecal excretion of bile acids was lower in the PUFA groups than in the CO group, whereas the sum of neutral sterols was similar in all groups. Plasma HDL2 (and VLDL + LDL) correlated positively, but HDL3 negatively, with fecal bile acid excretion. Accordingly, increased bile acid excretion does not seem to account for hypolipemia following intake of PUFA diets. PMID- 2921640 TI - Changes in plasma cholesterol density distribution of young adult male rats fed a high fat and cholesterol diet following maternal cholestyramine treatment. AB - The effects of feeding cholestyramine to pregnant rats, which has been shown to increase the fetal hepatic rate-limiting enzyme in cholesterol synthesis, HMG CoA reductase, on the plasma cholesterol density distribution was studied in the young adult male rat offspring before and after feeding a diet high in fat and cholesterol. As in previous studies, offspring of rats fed cholestyramine during pregnancy had a plasma total cholesterol level similar to controls when fed a low fat and cholesterol diet, but higher than controls when fed a 20% (wt/wt) fat plus 5% (wt/wt) cholesterol diet. Analyses of the plasma cholesterol density distribution by continuous gradient ultracentrifugation showed that, compared to control rats, rats born to dams fed cholestyramine had more cholesterol in the higher density regions of plasma before and after a 7-d high fat and cholesterol diet challenge. After a 4- or 7-d diet challenge, rats fed cholestyramine had 2-3 times more cholesterol in the d less than or equal to 1.006 g/ml range of plasma compared to the control offspring. The results suggest that long term changes in cholesterol metabolism due to early nutrition in the rat may include altered plasma or intestinal lipoprotein metabolism, rather than an effect specific to hepatic cholesterol synthesis. PMID- 2921641 TI - Effect of single oral doses of ascorbic acid on body temperature in healthy guinea pigs. AB - A series of experiments were conducted to examine the effect of single oral doses of ascorbic acid on body temperature in healthy guinea pigs. Fifteen male guinea pigs (approximately 200 g) were fed a nonpurified diet designed for rabbits (a scorbutogenic diet) ad libitum and received orally 2 mg L-ascorbic acid/100 g body wt daily. After acclimation, rectal temperatures were recorded hourly following five separate ascorbate dosage treatments: 0 (control dosage), 2, 10 or 50 mg ascorbic acid/100 g body wt, or 50 mg ascorbic acid and 0.07 mg indomethacin/100 g body wt. Mean body temperature was significantly elevated (P less than 0.05) after 1 h in animals receiving either the 10 or 50 mg dosage (+ 0.27 +/- 0.05 and + 0.41 +/- 0.07 degree C, respectively) compared to that in animals receiving the 2 mg dosage (-0.07 +/- 0.05 degree C), the recommended daily intake for guinea pigs. Changes in body temperature of animals receiving the 50 mg dosage plus indomethacin did not differ significantly from those reported with the 2 mg dosage. Thus, a single oral dose of ascorbic acid at levels 5-25 times the recommended intake, can elevate body temperature significantly in healthy guinea pigs, a phenomenon which is inhibited by indomethacin administration. PMID- 2921642 TI - Measurement of calcium and phosphorus fluxes during lactation in the rat. AB - Novel, two-compartment metabolic cages for rats were constructed to examine Ca and P fluxes during lactation. Four consecutive balance studies of 4 d each were performed in lactating rats and nonlactating controls. Lactating rats had dramatically higher intestinal absorptions of Ca and P resulting from both increased food consumption and elevated fractional absorptions of these elements. Urinary Ca excretion was reduced during lactation whereas urinary P excretion was unchanged. Endogenous fecal Ca excretion (determined by infusing 45Ca and dividing fecal 45Ca content by urinary 45Ca specific activity) was similar in lactating and nonlactating rats. In a separate study, pup retention of ingested Ca averaged 96%. Therefore, the difference in pup carcass Ca content between d 1 and 17 of age is assumed to equal 96% of the Ca transfer rate into milk. Similar calculations were applied to P. Milk transfer rates were determined to be 126 and 99 mg/d for Ca and P, respectively. These calculations indicate that 19% of the Ca transferred to milk was derived from the maternal skeleton with the maternal diet supplying the remaining Ca. This study provides the first comprehensive analysis of the alterations in Ca and P fluxes that occur during lactation in the rat. PMID- 2921643 TI - Effects of iron deficiency on metallothionein-I concentrations in blood and tissues of rats. AB - The effects of iron deficiency and of restriction of food intake on blood and tissue metallothionein-I (MT-I) concentrations in rats were investigated. Compared to ad libitum fed controls, MT-I concentrations in the blood cells of the iron-deficient rats were higher, whereas concentrations in pair-fed control rats were lower. Iron deficiency also increased MT-I concentrations in the bone marrow but concentrations in the liver were unchanged and those in the kidneys were reduced. The MT-I in the blood cells was associated mainly with the lighter cell fractions which were rich in reticulocytes. It is suggested that concentrations of MT-I in blood cells reflect erythropoietic activity. PMID- 2921644 TI - The enhancement of nonheme iron bioavailability by beef protein in the rat. AB - Beef protein was found to enhance the bioavailability of nonheme iron in the rat. Anemic rats were fed diets containing soy protein concentrate or rice bran as the source of nonheme iron with either lactalbumin or distilled water-washed beef, which was heme free. The criteria used to determine the relative biological value (RBV) of iron was the difference between the products of final hemoglobin x final weight and initial hemoglobin x initial weight during the repletion period. Animals fed diets with only lactalbumin as a source of dietary protein and graded levels of FeSO4 (RBV of FeSO4 = 100%) served as controls. The RBV of the endogenous iron in soy protein and rice bran was found to be 91 and 46%, respectively. Substituting washed beef for lactalbumin increased the RBV of soy protein iron to 96% (results not statistically significant) and of rice bran iron to 75% (results significant, P less than or equal to 0.05). These findings demonstrate the "meat factor" effect in the rat for the first time. Two days after completion of the 11-d hemoglobin regeneration period, the apparent absorption of iron was measured during a 60-h balance period. The apparent absorption of iron by rats fed diets containing beef tended to be higher, compared to animals fed diets containing lactalbumin. PMID- 2921645 TI - Copper status in the rat is affected by modes of copper delivery. AB - The purpose of this study was to determine whether the interaction between fructose and copper status can be affected by the mode of copper administration. Male Sprague-Dawley rats (n = 94) were fed from weaning diets that contained 0.65 0.85 mg copper/kg diet for 42 d. The experimental design of the study was a 2 x 2 x 3 analysis of variance: two types of carbohydrate (fructose, corn starch), two modes of copper delivery (orally or subcutaneously) and three different extrinsic copper levels (0, 1.5 or 3 mg/kg diet or 0, 11.25 or 22.5 micrograms Cu/d by injection). In the rats fed fructose, direct indicators of copper status such as plasma copper and tissue superoxide dismutase activity were increased to a much greater extent when copper was supplied subcutaneously rather than orally as part of the diet. In the starch-fed rats the effect of the mode of copper delivery on the levels of these indices was usually not significantly different. As a result, the feeding of fructose as compared to starch produced lower levels of direct indicators of copper status when copper was supplied in the diet but not subcutaneously. It appears that ingestion of fructose as compared to starch increases the requirement for copper and that the mode of copper administration that circumvents the gastrointestinal tract attenuates the fructose-copper interaction. Thus, the fructose-copper interaction occurs either during intestinal digestion and absorption, hepatic uptake of copper via the portal blood or its hepatic utilization. PMID- 2921646 TI - Influences of age and weaning on in vivo pancreatic protein synthesis in the lamb. AB - In vivo pancreatic protein synthesis rates were obtained from the uptake of L [3,4(n)-3H]valine co-injected with a flooding dose of unlabeled valine into 1-, 5 , and 8-wk-old suckling lambs, and 8-wk-old weaned animals. Protein fractional synthesis rate was 184%/d at 1 wk of age and 153%/d in 5-wk-old animals (P greater than 0.05). This lack of developmental change resulted from constant (P greater than 0.05) ribosomal capacities (total RNA/protein ratios) and efficiencies of protein synthesis (synthetic rates relative to RNA). No further alteration for protein fractional synthesis rate (144%/d) occurred in 8-wk-old suckling animals (P greater than 0.05). In contrast, 8-wk-old ruminants exhibited higher protein fractional synthesis rate (244%/d) than 8-wk-old suckling animals, although ribosomal capacity was markedly higher in both 8-wk-old groups than in youngest animals (P less than 0.05). The present findings clearly indicate that in vivo protein synthesis in the developing ovine pancreas depends primarily on age. Potentialities for increased rates of pancreatic protein synthesis, i.e., increases in total RNA content and ribosomal capacity appear between 5 and 8 wk of age in this species. At 8 wk of age, however, when lambs are generally weaned, solid food ingestion resulted in a rise for both fractional and absolute rates of protein synthesis, essentially because ruminants maintained a higher efficiency of protein synthesis than milk-fed animals (P less than 0.005). Finally, there was a relationship between pancreatic protein synthesis and protein intake in only ruminant lambs. PMID- 2921647 TI - Effect of dietary iodine on autoimmune thyroiditis in the BB Wistar rats. AB - Diabetes-prone BB Wistar rats were fed a modified AIN-76 diet providing the following amounts of iodine for 10 wk: 0.2 mg/kg diet (recommended amount); 1.0 mg/kg; 2.0 mg/kg; or 3.0 mg/kg. The thyroids were examined for gross and microscopic changes and sera were assayed for antibodies to triiodothyronine (T3), thyroxine (T4), and thyroglobulin (Tg). The body weights and food consumption of the rats fed 0.2 mg of iodine/kg were significantly lower than those of the animals fed higher amounts. Urinary iodine excretion reflected dietary intakes. The thyroids from animals fed 2.0 and 3.0 mg/kg were significantly (P less than 0.01) larger than those from animals fed 0.2 mg/kg. One rat fed 0.2 mg/kg and 2 rats in each group fed 2.0 and 3.0 mg/kg had extensive lymphocytic thyroiditis. Three rats fed 1.0 mg/kg, 6 fed 2.0 mg/kg and 6 fed 3.0 mg/kg had enlarged thyroids. Two rats fed 0.2 mg/kg, 2 fed 2.0 mg/kg and 6 fed 3.0 mg/kg had detectable Tg antibodies. These data suggest that high iodine intakes increase Tg antibodies, which may be associated with an increase in autoimmune thyroiditis in these animals. PMID- 2921648 TI - Dietary beta-carotene in rat models of gastrointestinal cancer. AB - The effect of dietary beta-carotene (BC) was investigated in models of gastric and colonic carcinogenesis. Male Wistar rats were fed a diet with 0.4% BC during weaning, then 0.2% BC throughout. Cancer in the stomach and small intestine was induced by giving 80 mg/l N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in drinking water for 52 wk, but BC failed to affect carcinogenesis under these conditions, although the incidence of gastric adenocarcinoma was reduced slightly. Neoplastic and nonneoplastic lesions in the liver, skin, and pancreas were also present to a similar extent with BC feeding and without BC. Colorectal cancer was induced by six 2 mg intrarectal infusions of MNNG per rat over a 3-wk period, with the rats held another 22 wk without an inhibitory effect by BC. Thus, 0.2% dietary BC failed to influence significantly the development of neoplasia induced by a direct-acting carcinogen in the gastrointestinal tract. PMID- 2921649 TI - The future direction of nutrition research: nutrition science reflects the principals of biological organization. PMID- 2921650 TI - Mechanisms of contour curvature discrimination. AB - Visual processing of contour curvature was investigated by measuring increment thresholds for curvatures from 0.31 to 25.4 deg-1. Curvature discrimination was assessed for three classes of stimuli: simple curved contours, high-frequency bandpass-filtered contours, and low-pass-filtered contours. High-frequency bandpass filtering had no effect on discrimination at low curvatures and only a modest effect at high curvatures. In contrast, low-pass filtering caused substantial threshold elevations at all curvatures. Thus the data lead to the surprising conclusion that high-spatial-frequency, orientation-selective mechanisms dominate curvature processing over the entire range of curvatures tested, a conclusion at odds with previous suggestions that large, low-spatial frequency filters are involved in analyzing low curvatures. The data are explained accurately by a two-process model for curvature extraction: at high curvatures the local-processing model proposed by Wilson [J. Opt. Soc. Am. A. 2, 1191 (1985)] fits the data well, whereas at low curvatures orientations are compared at points displaced a fixed distance along the tangent to the curve. PMID- 2921651 TI - Transient and steady-state response properties of movement detectors. AB - The transient and steady-state responses of movement detectors are studied at various pattern contrasts (i) by intracellularly recording from an identified movement-sensitive interneuron in the fly's brain and (ii) by comparing these results with computer simulations of an array of movement detectors of the correlation type. At the onset of stimulus motion, the membrane potential oscillates with a frequency corresponding to the temporal frequency of the stimulus pattern before it settles at its steady-state level. Both the transient and the steady-state response amplitudes show a characteristic contrast dependence. As is shown by computer modeling, the transient behavior that we found in the experiments reflects an intrinsic property of the general scheme of movement detectors of the correlation type. To account for the contrast dependence, however, this general scheme has to be elaborated by (i) a subtraction stage, which eliminates the background light intensity from the detector input signal, and (ii) saturation characteristics in both branches of each movement-detector subunit. PMID- 2921652 TI - Component analysis of spatial and spectral patterns in multispectral images. II. Entropy minimization. AB - In Part I [J. Opt. Soc. Am. A 4, 2101 (1987)] of this series, we developed a method for estimating both spatial patterns and spectral curves of components in a multispectral scene. This method does not need spatial and spectral information about the components but only multispread imagery data. The estimation is given as a feasible solution set satisfying the nonnegativity constraint for density and spectral response for all components at all pixels. In this paper, we estimate unique solutions for both the component patterns and the spectra from the feasible solution set. The solution is given by optimizing an entropy minimization criterion. This criterion enhances the spectral or spatial features of individual components. Two experimental results are shown to demonstrate the effectiveness of this method with biological and cytochemical specimens. The limitations of this method for unique pattern estimation are also discussed. PMID- 2921654 TI - Avoiding the overuse of radiographs. PMID- 2921653 TI - Retinal inhomogeneity and motion in depth. AB - The relation between retinal inhomogeneity and motion in depth was explored by means of a circularly symmetric but nonuniform stimulus pattern, designed to fit the inhomogeneity of the subject's retina. Radial motion of the quasi-sinusoidal rings of this target evokes an illusion of motion in depth: forward if the frontal-plane motion is centrifugal, backward if it is centripetal. Like the Plateau spiral, this stimulus produces strong motion aftereffects (MAE's) over a wide range of spatial and temporal frequencies. Over a much more limited frequency range, the forward MAE is significantly more adaptable than the backward MAE. This forward effect was found to occur only at very low spatial frequencies (approximately 0.05-0.5 cycles/deg at the fovea) and velocities near 20 deg/sec. The effect was destroyed by decentering the target or by varying its homogeneity so that it no longer matched the retina. These results suggest a hard wired collision-avoidance system. PMID- 2921655 TI - The Proplast/Teflon dilemma. PMID- 2921656 TI - Condylar displacement and temporomandibular joint dysfunction following bilateral sagittal split osteotomy and rigid fixation. AB - In this study changes in intercondylar width (ICW) and intercondylar angle (ICA) that occurred with rigid fixation after bilateral sagittal split osteotomy and mandibular advancement are documented and correlated with temporomandibular (TM) symptoms, magnitude of advancement, and mandibular shape. Even though individual changes occurred, there was no significant difference between the mean preoperative and postoperative ICA and ICW measurements. There was also no significant difference between the preoperative and postoperative incidence of TM pain or clicking. No correlation was found between the magnitude of advancement and the percent change in ICA or ICW, and the mandibular shape did not correlate to changes in ICW. This study suggests that screw osteosynthesis does not significantly change ICA or ICW. The fact that no significant increase in TM symptoms occurred indicates that the changes in condylar position that did occur were within the range of clinical adaptability of the patients. PMID- 2921657 TI - Free grafting of traumatically displaced or resected mandibular condyles. AB - A technique of free grafting of the mandibular condyle with a vertical ramus osteotomy is advocated in cases presenting with markedly displaced fracture dislocation of the condyle, in reconstruction of the TMJ after mandibular resection, and in providing access for vascular surgery approaches to the treatment of carotid aneurysms. The technique of free transplantation of the condyle did not result in any aseptic necrosis or any arthritic changes in 35 patients observed over a period of 3 to 15 years. All patients had excellent TMJ function. PMID- 2921658 TI - Effect of different surgical repair modalities on regeneration of the rabbit mandibular nerve. AB - A study was designed to evaluate the ability of the rabbit mandibular nerve to regenerate when exposed to crush and resection injuries, as well as to determine how differently sized resection injuries healed when repaired with either autogenous grafts or laminin-lined collagen tubulization. The nerve demonstrated a regenerative capacity over a 1-cm defect, with morphology and function that approximated normals, but could not span a 2-cm gap defect unaided. Crush injuries produced findings that were inferior to both those in normal nerves and in those with resections. In 1-cm defects, both grafting and tubular repairs produced similar results, with substantial recovery of neural function after 16 weeks. In 2-cm defects, autogenous grafting was superior to tubulization by both morphologic and functional assessment. Replacement of the lateral cortex of the mandible after nerve repair was shown to be unnecessary. The implications of these findings as they relate to nerve injury and repair in humans is discussed. PMID- 2921659 TI - Uniaxial pullout evaluation of internal screw fixation. AB - Multiple techniques of internal screw fixation are being used in clinical oral and maxillofacial surgery. This study evaluated the uniaxial pull-out strength of five commonly used screws and Kirschner pins placed by five different techniques. The pull-out strength of the Kirschner pins was significantly less (P greater than .0001) than that of the screws. The screw techniques did not differ significantly. PMID- 2921660 TI - Cowden syndrome: clinical and pathological considerations in two new cases. PMID- 2921661 TI - Pathogenesis and treatment of ranula: report of three cases. PMID- 2921662 TI - Postmortem examination of six maxillary core-vent implants: report of a case. PMID- 2921663 TI - Treatment for solitary eosinophilic granuloma of the mandible by steroid injection: report of a case. PMID- 2921664 TI - Age-related deposition of amyloid P component in normal human testis. AB - The distribution of amyloid P component in normal human testes from fetal life to old age was studied by a direct immunofluorescent technique on frozen sections. Amyloid P is readily and invariably detected in association with elastic fibres around seminiferous tubules and in blood vessels from the age of 30 years upwards. The same is true for most cases during the twenties, but in no case below the age of 18 was its presence demonstrable. PMID- 2921665 TI - Flow cytometric DNA analysis of 199 histologically favourable or unfavourable non Hodgkin lymphomas. AB - We have studied the nuclear DNA content of histologically favourable (n = 82) or unfavourable (n = 117) non-Hodgkin lymphomas (NHLs) diagnosed between 1957 and 1978 in the Tampere University Central Hospital. The DNA analysis was done by applying a trypsin digestion method to archival tumour samples. DNA aneuploidy was seen in 40 per cent of the unfavourable cases and in 10 per cent of the favourable cases, but varied considerably between different histological subtypes. The unfavourable cases showed high proliferative activity (S-phase fraction, SPF), while considerable variation in the SPF among the favourable NHLs was noted. Among the unfavourable NHLs, cases with DNA-aneuploid tumours had significantly (P less than 0.01) worse prognosis than stage and treatment matched cases with DNA-diploid tumours. In general, survival of the patients who had high SPF tumours was significantly lower compared with patients with low SPF tumours (P less than 0.01). However, SPF was not related to the prognosis in the unfavourable NHLs. We conclude that the flow cytometric DNA analysis revealed characteristic features in the favourable and unfavourable NHLs and may be useful in predicting the clinical outcome of patients. PMID- 2921667 TI - Mast cells in human lungs. AB - Mast cells were stained deeply in human lung tissue with acidic toluidine blue to obtain maximum numbers possible in paraffin sections. One hundred high-power fields were counted per section, and mean and median values summarized as mast cells per mm2. Immersion-fixed samples of fresh lung tissue (not bronchi) were taken as controls from seven patients after surgery, and showed mean values of 44.7 mast cells per mm2 after formalin fixation, and 51.9 per mm2 after Carnoy's fixative. Mast cell heterogeneity may explain these differences, but so could random variation between counts. In two patients with extrinsic allergic alveolitis (hypersensitivity pneumonitis), fresh lung tissue from open lung biopsies showed raised values of 90.8 and 101.9 mast cells per mm2, matching the high mast cell counts reported in bronchopulmonary lavage fluid in the condition. Control post-mortem lung tissue from two patients dying of non-pulmonary diseases showed mean values of 26.1 and 50.6 mast cells per mm2. Post-mortem lung tissue from three patients dying of asthma showed very low mean values of 4.7, 5.7, and 5.9 mast cells per mm2. Low mast cell counts due to severe degranulation have been reported before in the bronchi in asthma deaths, but not, to our knowledge, in the lung parenchyma. This finding implies a wider area of mediator release, and helps to explain the severity of the acute attack, and the fatal outcome. PMID- 2921666 TI - Immunoelectron microscopic studies of immune complex deposits and basement membrane components in IgA nephropathy. AB - The relationship between the immune complex deposits of mesangial IgA nephropathy and the basement membrane components, type IV collagen and fibronectin, has been investigated by an indirect immunogold technique in four cases of mesangial IgA disease. Using paraformaldehyde-fixed, Lowicryl K4M resin-embedded kidney, IgA, IgM and C3 were localized in the mesangial electron-dense deposits with 10 and 20 nm gold-labelled secondary antibodies. In the same glomeruli, type IV collagen and fibronectin were rarely present within the electron-dense deposits, although both were distributed throughout the remainder of the mesangial matrix with the exception of the subepithelial regions. These two components were also present within the glomerular basement membrane and localized mainly on the endothelial aspect. A similar distribution of the basement membrane components was seen in a control kidney processed in the same way. This technique gives reproducible results and has demonstrated for the first time the relationship between the mesangial immune complex deposits of mesangial IgA nephropathy and the basement membrane components of the matrix in which they are found. PMID- 2921668 TI - Macroscopic and microscopic early effects of tumour necrosis factor on murine Meth A sarcoma, and relation to curative activity. AB - Mice with solid Meth A sarcoma in the skin received an intravenous or intralesional injection of graded doses of recombinant human tumour necrosis factor (rTNF). Local treatment caused red discolouration and necrosis of the central portion of the tumour within 24 h over a larger range of doses than intravenous treatment. Effects showed a limited dose dependence and no significant correlation with subsequent cures, which were far more frequent after local treatment. A dose of rTNF that induced about equal macroscopic necrosis by both routes caused much more pronounced microscopic effects after local administration. Effects included mitotic arrest, granulocyte margination, endothelial damage, hyperaemia, congestion, oedema, and tumour cell necrosis. rTNF did not affect the Meth A cells in vitro. Locally injected skins showed moderate vascular effects which were more marked in tumour-bearing mice, but skin necrosis was absent. Data show that quantitative histology rather than macroscopically visible necrosis correlates with cure rates. A broad interference of rTNF with tumour blood supply seems to be a major cause of the induced necrosis. Granulocytes may be involved in vascular damage. The different effects of rTNF on skin and tumour indicate that tumour vasculature has enhanced susceptibility to rTNF and probably lesser repair capacity. PMID- 2921669 TI - Glandular changes in the rete testis: metastatic tumour or adenomatous hyperplasia? PMID- 2921670 TI - How do we teach pathology? PMID- 2921671 TI - Measurement of the S-phase duration in normal and abnormal human endometrium by in vitro double labelling with bromodeoxyuridine and tritiated thymidine. AB - The duration of the S phase of the cell cycle (ts) in the glands and stroma of normal, hyperplastic, and malignant endometrium was measured in vitro using a double labelling technique. Endometrial organ cultures were incubated sequentially in tritiated thymidine (3HTdR) and bromodeoxyuridine (BrdU) each for 1 h. Labelled cells were visualized in tissue sections using 3HTdR autoradiography and immunohistochemistry with an anti-(BrdU) antibody. Three populations of cells, single labelled with either 3HTdR or BrdU, and double labelled cells, were easily identified and ts was calculated from both the rate of influx into, and efflux out of S. There were no significant differences in ts in the different tissue types or between influx and efflux in the glands. However, in the stroma ts calculated from the rate of efflux was significantly shorter than that calculated from the rate of influx, suggesting that during the cell culture period the rate of cell efflux from S was greater than influx. This is the opposite to what would be expected in an exponentially growing cell population and suggests that there may be an effect from the culturing conditions. PMID- 2921672 TI - Changes in the cancer spectrum at autopsy: 1975-1984. AB - In an autopsy series of 8571 cases from 1975 to 1984, cancer deaths increased significantly, particularly in those cases over 60 years of age. A similar trend was seen in the mortality statistics from the district. Study of the degree of correlation between the frequency for the different types of cancer and the total deaths from that cancer at autopsy in the population supplies guidelines for use in assessing the relevance of autopsy findings to epidemiological research. It is stressed that without autopsy control monitoring of cancer in a population is incomplete and unreliable. An autopsy frequency of 40 per cent or more for the cancer in question in the population as a whole is required combined with series of 5-600 cases if satisfactory studies are to be initiated. Such conditions are difficult to fulfil for the less common types, but offer a valid approach to the monitoring of those types of cancer that are numerous enough to merit such attention. PMID- 2921673 TI - Pulmonary endocrine cells in chronic bronchitis and emphysema. AB - Pulmonary endocrine cells have been studied according to their immunoreactivity for neuron-specific enolase, gastrin-releasing peptide (GRP), calcitonin, leucine enkephalin, and serotonin in the lungs of subjects with chronic bronchitis and emphysema. The overall population was significantly greater in comparison with matched controls. The change was most marked in lobes affected by pneumonic consolidation, and did not affect equally the sub-populations of cells as identified by their content of peptide; the difference was much greater for calcitonin-containing cells than for those immunoreactive for GRP. This change may be the basis of the hypercalcitoninaemia and hypercalcitoninuria which have been reported in patients with inflammatory pulmonary disease. PMID- 2921674 TI - Different types of segmental sclerosing glomerular lesions in six experimental models of proteinuria. AB - From 133 to 615 glomeruli were examined in sections of kidneys from each of 60 animals, representing six rodent models of proteinuria. Particular attention was paid to the position of segmental lesions. Lewis rats given sheep anti-rat glomerular basement membrane antibodies had lesions almost exclusively at the glomerulo-tubular junction. Wistar rats on a diet of 24 per cent casein or with subtotal nephrectomy and a diet of 24 per cent soya had lesions mainly at the hilum. Wistar rats given bovine serum albumin had global lesions but virtually no segmental lesions. Wistar rats given puromycin aminonucleoside had lesions at the glomerulo-tubular junction and global mesangial abnormalities shortly after the treatment but later developed segmental lesions at all parts of the glomerulus. Untreated BUF/Mna rats had lesions at the glomerulo-tubular junction early in life but later had lesions at all parts of the glomerulus. Untreated NZB/NZW hybrid mice had various types of glomerulonephritis and also had lesions at the glomerulo-tubular junction. These findings showed that (1) segmental lesions at the glomerulo-tubular junction, or glomerular tip, occur in experimental animals, a fact not previously reported, and these tip changes are a common feature in several different models of proteinuria; (2) hilar segmental lesions are seen in conditions with hyperfiltration of protein; and (3) segmental lesions at various parts of the glomerulus are seen in some models of proteinuria and probably indicate late effects of random toxic damage to the glomerulus. Thus, there are at least three different types of segmental glomerular lesions in experimental animals--tip, hilar, and random--with different morphology and pathogenesis. It is likely that these findings can be extended to human renal diseases with segmental glomerular lesions. This will help to clarify the controversial and unsatisfactory term focal segmental glomerulosclerosis. PMID- 2921675 TI - The glomerular tip lesion: a distinct entity or not? PMID- 2921676 TI - Emphysema in the blotchy mouse: a morphometric study. PMID- 2921677 TI - How do we teach pathology? Bridging the gap between theory and practice. PMID- 2921678 TI - Pathological Society of Great Britain and Ireland. 158th meeting. 4-6 January 1989, London. Abstracts. PMID- 2921679 TI - Long-term pulmonary sequelae of meconium aspiration syndrome. AB - To determine the incidence of long-term sequelae after meconium aspiration syndrome (MAS), we studied 11 children who had MAS at age 8.2 +/- 0.2 years (mean +/- SD) and nine healthy control subjects with pulmonary function and exercise stress tests. The MAS children had evidence of mild airway obstruction, hyperinflation, and increased closing volumes in comparison with control values. During graded exercise stress tests on a treadmill, MAS children achieved normal maximal oxygen consumption and anaerobic threshold without a significant fall in arterial oxygen saturation or increase in CO2 tension. Exercise-induced bronchospasm occurred in four (36%) MAS subjects but in none of the control subjects. We conclude that children surviving MAS have long-term pulmonary sequelae, including airway obstruction, hyperinflation, elevated closing volumes, and airway hyperreactivity; yet they achieve normal aerobic capacity. These findings are similar, although less severe, than those after prematurity and bronchopulmonary dysplasia. PMID- 2921680 TI - Survival and clinical outcome in patients with cystic fibrosis, with or without neonatal screening. AB - After an experimental neonatal screening program for cystic fibrosis had been carried out in the Netherlands during 1973 to 1979, a follow-up study to evaluate the effects of neonatal screening was started in 1980. Although before 1980 the management of patients with cystic fibrosis was partly left to local hospitals, from the start of the follow-up program all patients in the study received similar treatment. A cumulative survival rate, calculated with exclusion of the patients with meconium ileus, showed at the age of 11 years a significantly better survival rate (p less than 0.05) for the 19 patients from the screened population (88%) than for the 25 patients from the nonscreened population (60%). Clinical condition was assessed on entry and at the age of 9 years in 16 screened and 20 nonscreened patients. On entry, comparison showed significantly better chest radiograph scores for the screened patients but no other significant differences. At the age of 9 years, after several years of similar treatment for all patients in the study, significantly better clinical (p less than 0.02) and chest radiograph scores (p less than 0.01), lower IgG levels (p less than 0.05), and higher vitamin A levels (p less than 0.01) were observed in the screened patients. Our study results suggest that early diagnosis and appropriate treatment may prevent serious deterioration and death at a young age, and may reduce the extent of early irreversible lung damage in patients with cystic fibrosis. PMID- 2921681 TI - Nocturnal home oxygen in the treatment of hypoxemic cystic fibrosis patients. AB - The effect of nocturnal oxygen therapy on mortality and morbidity rates and on progression of disease was tested in a double-blind, randomized trial of 28 subjects with advanced cystic fibrosis. Patients were selected on the basis that their awake arterial oxygen tension was less than 65 mm Hg when they were clinically stable. Oxygen was prescribed in 1 L/min increments to obtain an awake arterial oxygen tension of greater than or equal to 70 mm Hg. Subjects received humidified oxygen or room air from modified concentrators. They were enrolled over a 3-year period and followed for an average (+/- SD) of 26 +/- 9 months. The average number of hours per night of concentrator use was 5.3 +/- 3.2 hours in the air group and 7.0 +/- 1.9 hours in the oxygen group. Over the follow-up period there were four deaths in each group, and oxygen therapy had no significant effect on the frequency of hospitalizations. Progression of disease was ascertained from nutritional status, pulmonary function, blood gas values, exercise ability, and right ventricular ejection fraction response to exercise (as measured by equilibrium-gated radionuclide angiocardiography), and psychologic status was measured by standardized tests of mood, self-esteem, and cognitive function; group comparisons for the first year revealed no significant differences; however, school or work attendance was maintained in the oxygen group but deteriorated in the air group. Clinical signs of cor pulmonale were documented during follow-up in 10 patients in toto, and all lived at least 9 months from the onset of these signs. The lack of association between the onset of these signs and imminent death, or the usefulness of measurements of the maximal oxygen uptake during progressive exercise and the right ventricular ejection fraction response to exercise as prognostic indicators, suggest that death may not be the result of cor pulmonale. We conclude that nocturnal oxygen treatment in patients with cystic fibrosis did not appear to affect mortality rates, the frequency of hospitalizations, or the progression of disease; oxygen use should be instituted only after the development of symptoms related to hypoxemia. PMID- 2921682 TI - Home health care for children assisted by mechanical ventilation: the physician's perspective. AB - To obtain the physician's perspective concerning their care of children at home who required prolonged life-supportive medical technology, we conducted a mailed survey of 126 physicians caring for 25 children assisted by ventilators who had been discharged from 11 Illinois hospitals to their homes. The 51 (41%) physicians who responded included those practicing in many specialties from a variety of hospital settings throughout Illinois. The majority of respondents had less than 4 years' experience with ventilator-assisted children and were in their earlier years of practice. Most physicians surveyed had participated in discharge planning and maintained an active role with their patients at home after discharge. The majority believed that changes in ventilatory settings could be accomplished in the home and found hospitalization unnecessary for adjustments of the home care prescription. The physicians thought that the roles and responsibilities should be defined for both the tertiary and community-based physician before hospital discharge, and that development and support of resources at the community level were essential for the success of home care. PMID- 2921683 TI - Percutaneous femoral venous catheterizations: a prospective study of complications. AB - In a prospective, 45-month study, we compared the complication rates of percutaneously placed femoral and nonfemoral central venous catheters in critically ill pediatric patients. Forty-one percent of the 395 central venous catheters placed during this interval were femoral. Noninfectious complications were recognized for 2.5% of femoral catheters and 2.1% of nonfemoral catheters. Only three complications occurred with catheter insertion, all during nonfemoral attempts. Systemic infections that were possibly attributable to the central venous catheter were found in 3.7% of patients with femoral catheters and 7.3% of those with nonfemoral catheters. Femoral venous catheterization offers several practical advantages for central access over other sites. The low incidence of complications documented in this study suggests that the femoral vein is the preferred site in most critically ill children when central venous catheterization is indicated. PMID- 2921684 TI - Physiologic and methodologic issues regarding humidity therapy. PMID- 2921685 TI - Bulging fontanelle after immunization with diphtheria-tetanus-pertussis vaccine and diphtheria-tetanus vaccine. PMID- 2921686 TI - Risk of transmission of human immunodeficiency virus by bite of an infected toddler. PMID- 2921687 TI - Computed tomography scanning of the liver to determine efficacy of iron chelation therapy in thalassemia major. PMID- 2921688 TI - Low inspired gas temperature and respiratory complications in very low birth weight infants. AB - We analyzed 3705 measurements of inspired gas temperature in the first 96 hours of life, with concurrent measurements of ventilator variables and arterial oxygen tension, to determine any relationship to respiratory sequelae in 149 infants assisted by artificial ventilation. All management was with one type of ventilator (model IV100B, Sechrist Industries Inc., Anaheim, Calif.) and one type of humidifier (model MR 500, Fisher and Paykel, Auckland, New Zealand), and infants were placed under radiant heaters. Outcome for infants weighing greater than or equal to 1500 gm at birth was no different at low (less than or equal to 36.5 degrees C) versus high (greater than 36.5 degrees C) values of mean inspired gas temperature during the first 96 hours. However, infants weighing less than 1500 gm at birth had less respiratory morbidity at the higher temperatures; there was a reduction in the incidence of pneumothorax from 43% at low to 13% at high temperatures (p = 0.006) and a reduction in the severity of chronic lung disease, measured as mean Fio2 at 29 days in survivors, from 37.2% at low to 27.5% at high temperatures (p = 0.001). Clinical evaluation of the humidifier, as it was used in this study, suggested that temperature settings less than 36.5 degrees C were associated with inspired gas humidity between 28 and 36 mg H2O/L. For any humidifier, there may be a critical threshold for inspired gas humidity below which the risk of respiratory complications in very low birth weight babies is increased. This hypothesis requires rigorous scrutiny by controlled trial. In future studies, direct measurements of inspired gas humidity are needed to make a precise estimate of the optimal level. PMID- 2921689 TI - Airway reactivity as determined by a cold air challenge in infants with bronchopulmonary dysplasia. PMID- 2921690 TI - Cefotaxime and desacetylcefotaxime pharmacokinetics in very low birth weight neonates. AB - The single-dose pharmacokinetics of cefotaxime (CTX) and desacetylcefotaxime (dCTX) after a 50.0 mg/kg intravenous dose were evaluated in 18 very low birth weight neonates (13 male; 1015.6 +/- 349.8 gm; 28.4 +/- 2.4 weeks gestational age) during the first week of life. Microanalytic high-performance liquid chromatography was used to quantitate both CTX and dCTX from serum. A two compartment open model best characterized the disposition of CTX during a 24-hour post-dose period. The disposition of dCTX was adequately characterized by a one compartment model. The elimination half-life, apparent steady-state volume of distribution, and total body clearance of CTX (mean +/- SEM) were 4.44 hours, 0.461 +/- 0.027 L/kg, and 0.074 +/- 0.003 L/hr/kg, respectively. Peak concentrations (mean +/- SD) of dCTX (17.96 +/- 5.54 mg/L) occurred at 0.6 to 8.3 hours (5.9 +/- 1.9 hours) after CTX administration, and the apparent elimination half-life of dCTX was 9.36 hours. Comparison of CTX and dCTX pharmacokinetic parameters between very low birth weight neonates who weighed less than 1000 gm (n = 9; 703.3 +/- 46.6 gm; 27.0 +/- 0.8 weeks gestational age) and greater than or equal to 1000 gm (n = 9; 1328.8 +/- 48.6 gm; 29.8 +/- 0.5 weeks gestational age) revealed no significant differences, but significant linear correlations were found between gestational age and weight versus CTX half-life and total body clearance. Because of the prolonged clearance of both CTX and dCTX in the very low birth weight neonate, a CTX dose of 50 mg/kg every 24 hours may provide effective serum concentrations for susceptible infections outside the central nervous system. PMID- 2921691 TI - Continuous intravenous phenylephrine infusion for treatment of hypoxemic spells in tetralogy of Fallot. PMID- 2921692 TI - Hyponatremia and seizures after intravenous administration of desmopressin acetate for surgical hemostasis. PMID- 2921693 TI - Effect of ranitidine on twenty-four-hour gastric acidity in infants. PMID- 2921694 TI - Toxic effects of atenolol consumed during breast feeding. PMID- 2921695 TI - Nifedipine transfer into human milk. PMID- 2921696 TI - Identification during the postpartum period of infants who are at high risk of child maltreatment. AB - To determine whether clinicians correctly identify newborn infants who are at high risk of child maltreatment, we examined the outcomes of high-risk and non high-risk children. Infants who were born at Yale-New Haven Hospital from 1979 to 1981 and who were referred by clinicians during the postpartum period to the hospital's child abuse registry because they were considered at high risk of child abuse or neglect became the high-risk group. For each high-risk infant, a comparison infant was selected and matched according to date of birth, gender, race, and method of payment for the hospitalization. For both groups, the occurrence of maltreatment was ascertained by reviewing the medical records until the child's fourth birthday. Each injury for which medical care was sought was classified into one of seven categories (from definite child abuse to accident) by a pediatrician who was unaware of the child's risk status. Information also was recorded about nonorganic failure to thrive and changes in the child's caretaker. Maltreatment (defined as abuse or neglect) occurred more frequently in the high-risk group than the comparison group (adjusted matched odds ratio = 4.3; 95% confidence interval = 1.41, 6.93; p less than 0.001), as did poor weight gain from a nonorganic cause (matched odds ratio = 7.0; 95% confidence interval = 1.59, 30.79; p less than 0.01) and changes in the child's caretaker (matched odds ratio = 9.0; 95% confidence interval = 3.80; 20.55; p less than 0.001). We conclude that as early as the postpartum period, clinicians can identify some families who are at high risk of maltreatment and other major adverse outcomes resulting from poor parenting. PMID- 2921697 TI - Psychologic functioning in 8- to 16-year-old cancer survivors and their parents. AB - This study presents data on psychologic adjustment (self-concept, depression, locus of control, family environment, and parental distress) for a sample of 8- to 16-year-old long-term cancer survivors (n = 138) and their mothers, and for a sample consisting of a matched group of healthy children (n = 92) and their mothers. The null hypothesis of no group differences between survivors and control subjects was tested with respect to these variables. It was hypothesized that survivors with severe late effects would have poorer self-concepts, a more external locus of control, and more depressive symptoms than children with no or mild-to-moderate late effects. The children completed the Piers-Harris Self Concept Scale, the Nowicki-Strickland Locus of Control Scale, and the Children's Depression Inventory. Mothers completed the Family Environment Scale and the Derogatis Stress Profile. The majority of former patients are functioning within normative limits on these standardized measures, although their scores were lower than those in the comparison group. One-way analyses of variance on the dependent measures indicate that the children with severe medical late effects have a poorer total self-concept, more depressive symptoms, and a more external locus of control than those with no or mild-to-moderate late effects. Therapies for childhood cancer are now well standardized and many long-term deleterious effects are known, so children at risk can be identified readily and steps taken early in treatment to prevent or mitigate future psychologic problems. PMID- 2921699 TI - The foreskin and urinary tract infections. PMID- 2921698 TI - Psychosocial responses of children to cardiac pacemakers. AB - To examine the psychosocial responses of children and adolescents with a cardiac pacemaker and compare their responses to those of their peers, we evaluated 30 pediatric pacemaker patients, aged 7 to 19 years, and two age- and sex-matched comparison groups, including 30 patients with similar heart disease but without pacemakers and 30 physically healthy children, using standardized psychometric tests and a specific interview format. We postulated that children with pacemakers would experience greater stress in psychosocial adaptation. No significant differences on standardized measures of trait anxiety, self competence, or self-esteem were found between the pacemaker group and the comparison groups. In contrast, pacemaker subjects were significantly (p less than 0.05) more external in their locus-of-control orientation than were healthy subjects, suggesting a diminished sense of personal control and less autonomy. Pacemaker subjects, particularly the older ones, had significantly (p less than 0.05) greater knowledge of pacemaker systems than did subjects in the other two groups, facilitating the use of intellectualization as a coping mechanism. The pacemaker patients were likely to be as fearful of social rejection as of potential pacemaker failure. All three groups identified potential negative peer reactions toward an individual with a pacemaker. The patients with cardiac disease but without pacemakers and the healthy subjects perceived significant (p less than 0.05) social and emotional differences between patients with pacemakers and their peers, but the pacemaker patients did not view themselves as different from their peers. This study demonstrates healthy psychosocial adaptation of children with cardiac pacemakers. Although these children appear to cope effectively with the stress of their life situation through the use of denial and intellectualization, they may experience problems both in the development of autonomy and in social isolation and rejection. PMID- 2921700 TI - Gastric outlet obstruction in chronic granulomatous disease. PMID- 2921701 TI - Leukocyte studies in diagnosis of neonatal sepsis. PMID- 2921702 TI - Management of pain caused by pancreatitis. PMID- 2921703 TI - Nonoliguric hyperkalemia in preterm neonates. PMID- 2921704 TI - Tracheal suction in meconium-stained neonates. PMID- 2921705 TI - Maternal hyperparathyroidism and neonatal rickets. PMID- 2921706 TI - Use of naloxone in asphyxiated neonates. PMID- 2921707 TI - Hypercalcemia associated with normal 1,25-dihydroxyvitamin D concentrations in a neonate with factor IX deficiency. PMID- 2921708 TI - The gingival effects of dental airpolishing as evaluated by scanning electron microscopy. AB - An air-powder abrasive system was tested among 20 volunteers, who had healthy gingiva or slight gingivitis, but no periodontal pockets. Impressions of randomly selected areas (n = 103) were taken before and after airpolishing and positive replicas were prepared for scanning electron microscopy (SEM). Gingival bleeding increased statistically significantly (p less than 0.001) during the treatment. Also gingival erosive changes were increased when using airpolishing technique (p less than 0.001). The erosive changes observed by SEM and the subjective symptoms during and after the operation positively correlated to the presence of gingival inflammation (p less than 0.001). It can be concluded that also the negative aspects of the airpolishing technique should be taken into consideration, especially when operating near the gingival margin. PMID- 2921709 TI - Quantification of bacterial penetration in spontaneous periodontal disease in beagle dogs. AB - The role of bacteria in the pathogenesis of periodontal disease is controversial. Although bacterial penetration has been demonstrated in human periodontitis, relationships of bacteria to varying levels of periodontal health in other animals has not been well documented. In this study of beagle dog periodontium, bacteria were counted within the various tissue regions of sites which exhibited periodontal health, gingivitis, or periodontitis. Affected sites within whole block sections from two aged beagle dogs were prepared for investigation by light (LM) and scanning electron microscopy (SEM), and bacterial counts were subjected to statistical analysis for differences. Periodontitis sites viewed with LM had more bacteria than healthy sites. Neither LM nor SEM observations yielded any other differences in bacterial counts between the levels of periodontal health. When viewed using SEM, the sulcular epithelium had more bacteria than the other tissue regions in diseased sites. Relative to the number of bacteria in plaque, however, counts from all microscopic observations were very low. These findings indicate that the presence of bacteria within the periodontium is of questionable significance in the pathogenesis of spontaneous periodontal disease in beagle dogs. PMID- 2921710 TI - The effect of an antimicrobial mouthrinse on early healing of gingival flap surgery wounds. AB - A randomized double-blind crossover design study using 25 patients requiring bilateral gingival flap surgery was completed. The effect of rinsing postsurgically three times daily with an antimicrobial mouthrinse or physiological saline on dental plaque formation, gingival inflammation, bleeding, wound healing, and patient comfort was evaluated at 7, 14 and 28 days. The antimicrobial rinse was statistically significantly 28.9% more effective than saline at seven days for reducing plaque. It was also significantly more effective for improving wound healing at day 7 as measured by edema (p less than 0.04). There were no significant differences in gingival index scores or bleeding at any time period. Use of an antimicrobial mouthrinse may be an effective aid in early healing of gingival flap surgery wounds. PMID- 2921711 TI - Different cross-linked types of collagen implanted in rat palatal gingiva. AB - Collagen membrane preparations were manufactured with the aim of enhancing wound healing following periodontal surgery. After crosslinking by various processing methods (with ultraviolet and hexamethylenediisocyanate) and to various extents, two types of collagen (atelocollagen and tendon collagen) were implanted into a dissection site within palatal gingival tissue. The time course of healing responses was investigated histologically. Collagen implantation was found to accelerate fibrous connective tissue attachment to the root surface and inhibit apical migration of the junctional epithelium. Cross-linked atelocollagen was superior in biocompatibility to the other collagen membranes studied. PMID- 2921712 TI - The effect of health beliefs on the compliance of periodontal patients with oral hygiene instructions. AB - Problems of patient compliance in periodontics are evident. This study explored factors which may contribute to the degree of adherence. Using the "Health Belief Model" a questionnaire was constructed and administered to 120 patients of the Department of Periodontology, University of Frankfurt Dental School. Compliance of these patients during the hygienic phase was assessed using a bleeding index. The data set for statistical evaluation comprised 96 patients. The loss was due to missing of appointments and incomplete questionnaires. There was no significant correlation between patient compliance on the one hand and sociodemographic variables (age, sex, family status), disease parameters, and the health beliefs "susceptibility," "barriers," "dentist-patient-relationship," and "experience with therapy" on the other hand. "Motivation," "seriousness," "benefits," "experience with affected organ," and tooth-loss-index were significant predictors with Spearman correlation coefficients running from 0.17 to 0.32. When the predictor variables were combined the coefficient was 0.59. This study further supports the assumption that health beliefs play a significant role in the determination of health related behavior. PMID- 2921713 TI - Influence of age on August levels of pineal immunoreactive arginine vasotocin in rats. AB - The present study was undertaken to evaluate carefully the influence of age on physiological levels of arginine vasotocin-like peptide in rat pineal glands. Glands were collected from male and female rats aged 13, 33, 53, and 73 days on August 4, 12, and 19, 1984. Individual extracts were assayed for arginine vasotocin (AVT) by radioimmunoassay. The results confirm our previous observation that rat pineal AVT immunoactivity (iAVT) increases significantly during August each year; and in this study, each group of rats reached the same peak level of iAVT (700-750 pg/gland) regardless of age or gender. Thus we do not confirm a previously reported decrease in AVT activity with age. In our studies thus far, season of the year is the physiological variable with the most significant influence on pineal AVT activity levels. PMID- 2921714 TI - Catecholaminergic mechanisms mediate hypothermia-induced elevations in pineal gland N-acetyltransferase in neonatal rats. AB - The newly born of many mammalian species are ectothermic, and it is possible that biochemical processes important for the metabolism of endocrine hormones might vary with alterations in the environmental temperature. Temperature-induced fluctuations in pineal gland N-acetyltransferase activity were investigated in 4 , 12-, and 20-day-old rats placed for 4 hr in 23 or 34 degrees C environments. Enzyme activity increased dramatically in ectothermic 4- and 12-day-old animals exposed to the 23 degrees C environment, but not in endothermic 20-day-old rats. The elevations in daytime pineal gland NAT activity seen in cold-exposed animals were absent in rats previously subjected to chemical sympathectomy induced by 6 hydroxydopamine, or in animals treated with the beta-noradrenoceptor antagonist drug propranolol. Catecholaminergic nerves and beta-noradrenoceptors known to be important for light-induced changes in mammalian pineal gland biochemistry also appear essential for environmental temperature-dependent elevations in neonatal pineal N-acetyltransferase activity. PMID- 2921715 TI - Unusual configurations of endoplasmic reticulum in pinealocytes of the Djungarian hamster (Phodopus sungorus). AB - Ultrastructural observations of the pineal gland of Phodopus sungorus revealed different morphological forms of endoplasmic reticulum. These included crystalloids composed of 200A-wide tubules with an intervening space of 200A and connected at right angles to form a rectangular lattice; complexes of undulating 500A-wide tubules in an electron-dense cytoplasmic matrix; and stacks of flattened cisternae covered with granular electron-dense material. All these structures are continuous with the surrounding endoplasmic reticulum. Frequently one structure is directly connected with another. The exact function of these structures derived from the endoplasmic reticulum is still unclear, but they can be assumed to be morphological features of augmented secretory activity. PMID- 2921716 TI - Regulation of melatonin in the harderian glands of golden hamsters. AB - A daily rhythm in melatonin concentration in Harderian glands (HG) of female golden hamsters is described and is characterized by significant reductions following lights-on. Concentrations in HG of intact or pinealectomized males are low and consistent over a 24-hour period. Castration of males is accompanied by increased levels of melatonin in the HG to approach those of females. When castrated males are exposed to short photoperiods, however, melatonin levels are typically low. Levels of serotonin (5-HT), 5-hydroxytryptophan (5-HTP), and 5 hydroxyindoleacetic acid (5-HIAA) are extremely variable in GH of both males and females, precluding definitive conclusions. Melatonin concentrations in HG of females do not appear to be affected by light or stress per se, nor are the superior cervical ganglia the pathway by which concentrations are modified. PMID- 2921718 TI - Nursing research with preoperational age children: the use of standardized tests. AB - Very few standardized tools are currently available for nurses who work with preoperational age children. This article suggests steps to adapt research tools used with older children for use with younger children. PMID- 2921717 TI - Modulating action of melatonin on serotonin-induced aggravation of ethanol ulceration and changes of mucosal blood flow in rat stomachs. AB - Effects of melatonin and serotonin on ethanol ulceration and mucosal blood flow in the rat stomach were investigated. Melatonin and serotonin (5-HT) administration did not produce observable gastric injury in the ex vivo stomach, but the 5-HT dose dependently reduced glandular mucosal blood flow (GMBF) in this organ. Ethanol depressed GMBF and induced visible glandular mucosal injury. The latter effect was prevented by melatonin preincubation. Serotonin pretreatment aggravated the gastric mucosal injury and GMBF changes induced by ethanol; these actions were partially reversed by melatonin. The findings indicate that the GMBF and gastric injury are related; the reduction in FMBF, however, may not be the sole factor responsible for ulceration. The antagonistic effects of melatonin on 5-HT action on the stomach suggest that melatonin may act as a modulator for 5-HT action on the gastrointestinal tract. PMID- 2921719 TI - Compliance with chronic illness regimens: school-aged children and adolescents. AB - More chronically ill school-aged children and adolescents are surviving into adulthood due to recent medical advances and modern technology. However, noncompliance rates are higher among adolescents than adults. Noncompliance is costly, can lead to complications, and may be life-threatening. Several models of compliance are discussed. Variables described in recent research as related to noncompliance (personal, family, and illness factors) are discussed. Those factors that emerged as most important in adolescent compliance were self-esteem, social functioning, and perceived autonomy. It appears that psychological needs may compete and conflict with the need for adherence to illness regimens in adolescence. PMID- 2921720 TI - Night terrors: strategies for family coping. AB - This article discusses the occurrence of night terrors (parvor nocturnus) in children. The characteristics of a typical night terror incident are described, as are the common parental reactions to such frightening events. Nurses who work with children and families need to know about the etiology and clinical course of night terrors. They need to be able to differentiate night terrors from other sleep disturbances and determine possible ways to alleviate the occurrences. This article emphasizes assessment, anticipatory guidance, education, and counseling. A practical guide for parents is included to provide families with information on ways to cope with night terrors. PMID- 2921721 TI - Implementation of a clinical study of a pain management program for pediatric oncology patients. PMID- 2921722 TI - Nihilism and the young. PMID- 2921723 TI - The games we play. PMID- 2921724 TI - Development and use of the Preschool Behavior Inventory. AB - This article is on the development and use of the Preschool Behavior Inventory (PBI), a mental health screening tool for preschool children. The PBI was developed to fulfill the need for a valid and reliable mental health screening tool for preschool children that could be completed by parents in a brief period of time in a variety of settings, including well-child clinics, pediatricians' offices, outpatient clinics, hospitals, Head Start programs, day-care centers, and preschools. The validity and reliability of the PBI were tested in three phases on 433 preschool children in Tacoma-Pierce County, WA. The children were in day care, preschools, or early childhood screening programs. To test the validity and reliability of the PBI, comparisons were made between parents' ratings on the PBI and ratings on the Mental Health Rating Scale completed by preschool teachers, day-care providers, and/or mental health specialists in the Tacoma-Pierce County Health Department. Based on these studies, the PBI was found to have good validity and reliability. PMID- 2921725 TI - Blue Healon. AB - A random prospective study comparing clear sodium hyaluronate (Healon) and blue Healon was done in 50 patients who had routine extracapsular cataract surgery with lens implantation. Blue Healon was more visible and easier to remove. For this reason there was less residual Healon postoperatively in the blue Healon group, with slightly fewer cells and less flare and blood in the immediate postoperative period. There were no other differences and the mechanical properties of the two Healons were the same. PMID- 2921726 TI - Surface quality of intraocular lenses. AB - We observed circular furrow-like patterns on the implanted intraocular lens surface in postoperative follow-up examination by specular microscopy. The patterns may have been deep lathe-cut marks or compression-related marks on the optics. Specular microscopy, polarized light microscopy, and scanning electron microscopy detected a similar circular mark on the optic surface of a control intraocular lens of the same model. A reconsideration of surface quality is indicated. PMID- 2921727 TI - Consultation section. PMID- 2921728 TI - Ocular pneumoplethysmography after lens implantation. PMID- 2921729 TI - Free-hand precutting of transverse keratotomies. PMID- 2921730 TI - Analysis of astigmatic keratotomy. AB - Eighty-two keratotomy procedures were performed for both idiopathic and postsurgical astigmatism or myopic astigmatism and analyzed for efficacy using vector and linear regression analysis. Delta keratometry values (delta K) were computed for each case as delta K in the desired axis of effect using vector analysis. Six different procedures were compared including both intersecting and nonintersecting trapezoidal keratotomy, relaxing incisions with compression sutures, T cuts with radial keratotomy, T cuts alone, and RK with elliptical optical zones. Our results showed that the greatest shifts occurred in the trapezoidal groups, whereas the most predictable effects occurred in the relaxing incision/compression suture group. Astigmatic keratotomy is capable of producing large shifts in corneal astigmatism; however, the accuracy of these procedures remains highly variable. PMID- 2921731 TI - Refractive evaluation of astigmatic keratotomy procedures. AB - We evaluated the efficacy of three transverse incision astigmatic keratotomy procedures using a vector analysis that enabled us to determine the magnitude of the effect and the axis in which it occurred. These procedures were used for low levels of astigmatism (0.5 diopter [D] to 3.75 D): (1) staggered, radial-touching transverse (T) incisions, (2) non-radial-touching T incisions, and (3) T incisions with interrupted radial. Most procedures were performed in conjunction with radial keratotomy for spherical correction of myopia. The non-radial touching T procedure was the least effective method of reducing astigmatism. The staggered, radial-touching T and T with interrupted radial procedures were equally effective in reducing over 93% (on the average) of the preoperative astigmatism. Of these two procedures, the T with interrupted radial procedure was the most accurate, with the effect of the surgery deviating less than ten degrees from the desired axis in over 70% of the eyes. PMID- 2921732 TI - Paired transverse relaxing keratotomy: a combined technique for reducing astigmatism. AB - Phacoemulsification, posterior chamber intraocular lens implantation, and corneal relaxing incisions were performed as a combined procedure in 75 eyes with preexisting with-the-rule or against-the-rule astigmatism. The results of this study confirm that this technique can safely reduce preexisting low and moderate astigmatism with a greater likelihood of achieving excellent uncorrected visual acuity. PMID- 2921733 TI - Transverse astigmatic keratotomy combined with phacoemulsification and intraocular lens implantation. AB - Transverse astigmatic keratotomy is a surgical technique to correct preoperative corneal astigmatism during cataract surgery. The operative technique is described and the results of my first 40 cases are reviewed. The average keratometric astigmatism for this group before surgery was 2.6 dipoters (D). The average reduction in astigmatism was 1.5 D, which yielded a final residual average astigmatism of 1.1 D after surgery. Cases of substantial astigmatism showed the most improvement. Less improvement was seen in cases of minimal preoperative astigmatism. No increase in net keratometric astigmatism was seen in any of the eyes studied. Minor complications were limited to several small corneal abrasions created by the front-cutting diamond blade and one late temporary wound dehiscence. The only serious complication was one case of corneal macroperforation. Recommendations for handling this complication and future high astigmatism cases are given. PMID- 2921734 TI - Correction of preexisting astigmatism at the time of small incision cataract surgery. AB - To reduce preexisting astigmatism in patients having cataract surgery, paired keratotomy incisions of graded lengths were performed at the time of cataract extraction. Small incisions, made possible by foldable silicone implants, were used to make the correction more accurate. The results obtained in 48 patients are analyzed. It appears that this technique is safe, quick, and helpful in reducing preexisting astigmatism. PMID- 2921735 TI - Small incisions to control astigmatism during cataract surgery. AB - Astigmatic changes in three series of cataract surgical procedures were compared. Two series comprised eyes having phacoemulsification and implantation of a foldable silicone lens through a 3.0 mm to 4.0 mm incision or a 5.8 mm diameter polymethylmethacrylate (PMMA) lens through a 6.0 mm incision. The third series comprised eyes having a planned extracapsular cataract extraction (ECCE) procedure through a 10.0 mm incision and implantation of a PMMA posterior chamber lens. Surgically induced cylinder changes were compared by examining preoperative and postoperative dioptric cylinder power changes without regard to axis changes and by using vector analysis to compute induced cylinder for cases with axis changes. Both phacoemulsification series had similar mean induced cylinder levels, which were significantly less than mean induced cylinder in the ECCE group at both three and six months after surgery. Over 70% of the eyes in the two small incision phacoemulsification groups achieved an uncorrected visual acuity of 20/40 or better at three months, whereas only 28% of the ECCE group achieved that acuity. We concluded that the phacoemulsification procedure induced significantly less astigmatism and provided faster visual rehabilitation than the ECCE procedure. Furthermore, the use of small diameter PMMA IOLs inserted through small incisions minimized surgically induced cylinder in a way comparable to the use of foldable silicone implants, while maintaining good visual results with fewer postoperative complications. PMID- 2921736 TI - Corneal press-on ruler for astigmatic keratotomy. PMID- 2921737 TI - U-shaped anterior capsulotomy for in-the-bag intraocular lens placement. PMID- 2921738 TI - Psychological issues in childhood cancer survivors. PMID- 2921739 TI - Offspring of childhood cancer survivors. PMID- 2921740 TI - Correlational research. PMID- 2921741 TI - BCNU (carmustine). PMID- 2921742 TI - Survivors make my day. PMID- 2921743 TI - The patient failed therapy. PMID- 2921744 TI - Orthodontic therapy for the restorative patient. Part I: The biomechanic aspects. AB - The integration of interspecialty treatment before the restorative and prosthodontic efforts of the dentist can eliminate conditions that have the potential to jeopardize successful completion of the proposed treatment. Adult dentitions that have deteriorated because of neglect, fear, caries, extractions, or trauma can be restored to stability, health, function, and esthetics. In "Part I, The biomechanic aspects," the orthodontic paralleling of proposed abutment teeth displays premolar (buccolingual) and molar (mesiodistal) uprighting procedures that achieve improved force distribution to these teeth. Molar intrusion (occlusoapical) to improve an occlusal plane distribution of adverse forces to the proposed opposing fixed partial denture is discussed. These vexing problems facing successful reintegration of the altered states of occlusal relationships frequently can be answered by the incorporation of preprosthodontic corrections. PMID- 2921745 TI - Transferring anterior occlusal guidance to the articulator. AB - Anterior disclusion has become accepted as an optimal therapeutic model in the restoration of the anterior dentition. The ability to achieve anterior disclusion is influenced by the anterior determinants of esthetics, phonetics, skeletal relation, tooth position, abutment distribution, and alveolar bone support in addition to the posterior condylar determinants. Temporary restorations are made to incorporate these factors and it becomes necessary to transfer the information to working models of the articulator. A technique is described whereby a wax or silicone index fixed partial denture is made at chairside, duplicating the temporary restoration that is directly transferable to the working casts of the articulator. This technique allows the technician to make final restorations according to the index fixed partial denture, thus incorporating the anterior determinants of occlusion in conjunction with the posterior condylar determinants specific to each patient. PMID- 2921746 TI - Analysis of rotation centers of various mandibular closures. AB - Wax interocclusal records of five subjects made during three types of mandibular closing movement at various degrees of jaw opening were successively placed between mandibular and maxillary casts that were mounted on an articulator. Recording pins inserted into the lateral sides of the casts were used to record the amount of movements. The rotation centers were then calculated and the following results were obtained. (1) For the terminal hinge closure in which the mandible was guided by the chinpoint, no statistically constant rotation center was observed. (2) For the most retruded closure of the mandible in which each subject was asked to make the most retruded position by his own effort, a constant rotation center was found in two of five subjects. (3) For habitual closure of the mandible no constant rotation center was observed, and where the interocclusal distance was less than 1 mm the mandible seemed to close perpendicular to the occlusal plane. PMID- 2921747 TI - A comparative study of the strength of aluminous porcelain and all-ceramic crowns. AB - This study compared the breaking strengths of all-ceramic crowns constructed with aluminous porcelain, the Cerestore system, and the Dicor system on an anterior tooth preparation. Fifteen crowns from each group were constructed to comparable dimensions on dies from the same master die. Ten crowns from the same group were cemented on the master die and loaded until catastrophic failure. Five crowns from each group were embedded and sectioned to examine internal adaptation. No significant difference was found between the load necessary to produce failure in the aluminous porcelain and Dicor crowns and the load needed to initiate crack formation in the Cerestore crowns. However, seven of the 10 Cerestore crowns showed a two-phase failure pattern; the difference between crack initiation and catastrophic failure was significant. Within the limitation of this study, neither the Cerestore (high alumina core) nor the Dicor (castable glass-ceramic) produced an all-ceramic crown superior to the current aluminous porcelain crown. PMID- 2921748 TI - Antimicrobial activity of calcium hydroxide liners on Streptococcus sanguis and S. mutans. AB - The antimicrobial activity of 10 calcium hydroxide liners on Streptococcus sanguis and S. mutans was studied. One hundred plates of tryticose soy agar-sheep red blood cells (10%), each with four distinct 3 mm diameter wells, were divided into two groups of 50. One group was inoculated with S. sanguis and the second group with S. mutans. A 4 mg liner was placed in each of three wells; the fourth well was left empty as a control. Plates were incubated at 37 degrees C and observed at 24 hours, 48 hours, and 7 days. All liners inhibited growth of both organisms. The inhibitory zones for S. mutans were larger than inhibitory zones for S. sanguis for all tested liners. Life Fast Set material had significantly less inhibitory effect on S. mutans. VLC Dycal, Life, and Life Fast Set materials had significantly less inhibitory effect on S. sanguis at p = 0.05. PMID- 2921749 TI - The labial endodontic access: a rational treatment approach in anterior teeth. AB - Labial endodontic access is an alternative to the conventional lingual endodontic access in permanent teeth. The labial approach facilitates visibility and provides direct access to the root apex. Current restorative procedures offer improved methods to overcome the esthetic impairment resulting from this approach. Labial access is especially beneficial for patients with limited mandibular opening. Other indications are in Angle's class II division 2 dentitions or in teeth with resin-bonded cast restorations. Anatomic studies for the single tooth that corroborate the labial endodontic approach are reviewed. PMID- 2921750 TI - The orbital shell: an aid in positioning the ocular component and verifying margin contours for oculofacial prostheses. AB - The correct location of the orientation (conversational gaze) of the ocular component is vital to esthetically pleasing oculofacial prostheses. This location should be verified before time and energy are spent on sculpturing the oculofacial prosthesis. A technique is described that uses a clear acrylic resin shell as a matrix and Play-doh material as a support medium to position and support the ocular component to verify the orientation. In addition, the thin acrylic resin shell can be used to refine border inaccuracies that may exist clinically. PMID- 2921751 TI - Nasopharyngeal impression technique for fabrication of a radiation carrier. AB - A new technique for intracavitary application of Iridium 192 seeds in carcinoma of the nasopharynx is described. This technique allows for accurate construction of a nasopharyngeal carrier that permits the radiotherapist to deliver an adequate dose of irradiation to the nasopharynx. PMID- 2921752 TI - The relationship between condylar guidance and temporomandibular joint clicking. AB - The association between condylar inclination and temporomandibular joint (TMJ) clicking was tested by measuring the angles of condylar guidance in the sagittal plane during opening and closing movements in 12 subjects with temporomandibular joint clicks and 16 subjects without TMJ clicks. Each subject had tracings made by using a customized functional clutch. All subjects had full dentition and were without symptomatic mandibular dysfunction. Condylar inclinations were measured in parasagittal tracing planes. The travel path of the hinge axis of the condyle's movements was recorded, directly formed, and compared with a four component axiograph recording that used the axis-orbital plane as a reference for the subjects. The measurements of angles along several distances (millimeters) of condylar guidance from the axis-orbital plane were obtained and evaluated. The measurements were made in the sagittal plane and through opening-closing movements starting from the actual occlusal vertical dimension of each subject. The results do not support the hypothesis that mean angles of the condylar guidance are significantly different in the group with TMJ clicking compared with the group without TMJ clicking. PMID- 2921753 TI - Prognostic features of value in the management of temporomandibular joint pain dysfunction syndrome by occlusal splint therapy. AB - Fifty consecutive patients diagnosed as suffering from a temporomandibular joint pain-dysfunction syndrome that required occlusal splint therapy were studied. Particular attention was given to observable features that could be analyzed during resolution as indicated by using successive visual analogue scales for pain assessment. By photographing occlusal registrations before and after each splint adjustment visit it was shown that the stabilization of occlusal patterns as resolution progressed gave a good indication of the success of treatment in most patients. In patients in which stabilization of patterns occurred but pain continued there was an indication of a complicating psychosocial disorder. PMID- 2921754 TI - A mathematical method for calculating the compensating anterior stop pin setting of a semiadjustable arcon articulator. AB - The geometry of a semiadjustable arcon articulator and development of mathematical formulae to calculate the setting of the anterior stop pin that compensates for the thickness of the interocclusal centric relation record are discussed. Measurements of the facebow mounted maxillary cast and interocclusal centric relation record are used in these formulae. Testing on 30 diagnostic mountings indicated that the formulae can reliably predict the amount of anterior stop pin opening necessary to allow near parallelism of the maxillary and mandibular bows of the articulator when the interocclusal centric relation record is removed and the mounted casts are brought into occlusion. The vertical component of dental malocclusion is identified as a source of variability in the setting of the anterior stop pin and therefore in the geometry of the articulator; it is defined as a need for further study. PMID- 2921755 TI - The use of microwave energy for processing acrylic resins. AB - Test strips of five different resins were processed with (1) microwaves by using a kitchen-type microwave oven, and (2) a conventional water bath. The strips were tested for hardness, porosity, and transverse strength. The results showed no significant difference between resin strips cured by either method. Maxillary dentures were waxed on stone casts of an aluminum model in another study. The dentures were processed with the same five resins, half by using microwave energy and the remainder with the water bath. The adaptation of the processed dentures to the aluminum cast was measured with feeler gauges. The results showed no statistically significant differences between dentures cured by either method. These studies demonstrated that the important physical characteristics of microwave-cured resin are approximately the same as resin cured in a conventional water bath. Curing dentures by microwave energy has the advantages of reduced curing time, ease, and cleanliness. PMID- 2921756 TI - Use of mouthguards during tooth preparation for patients with extreme tooth hypersensitivity. AB - During tooth preparation, the air and water from a dental handpiece occasionally cause painful stimulation of hypersensitive teeth. Use of mouthguards may be an alternative for the management of patients with tooth hypersensitivity. PMID- 2921757 TI - Crown cementation: put a handle on it. AB - During tooth preparation, the air and water from a dental handpiece occasionally cause painful stimulation of hypersensitive teeth. Use of mouthguards may be an alternative for management of patients with tooth hypersensitivity. PMID- 2921758 TI - An evaluation of the criteria used to diagnose mandibular dysfunction with the mandibular kinesiograph. PMID- 2921759 TI - Can electrical stimulation be used to establish a physiologic occlusal position? PMID- 2921760 TI - An evaluation of the criteria used to diagnose mandibular dysfunction with the mandibular kinesiograph. PMID- 2921761 TI - Promoting power and control in the elderly client. PMID- 2921762 TI - Handle with care: the geriatric patient in the ambulatory surgery environment. PMID- 2921763 TI - A practical system for narcotic control within the OR/PACU. PMID- 2921764 TI - Practical points in the management of laryngospasm. AB - Laryngospasm is an emergency situation and must be promptly recognized. Without quick recognition and proper treatment, the patient's airway may occlude, leading to respiratory arrest followed by cardiac arrest. Because laryngospasm is a potential life-threatening postoperative event, the PACU nurse must remain a guardian of the airway. PMID- 2921765 TI - Is midazolam a dangerous drug? AB - Midazolam can be used to achieve anxiolysis, to provide conscious sedation with anterograde amnesia during operations performed under local or regional anesthesia, to induce general anesthesia, and as part of a balanced anesthetic. Understanding the pharmacologic properties and potential adverse side effects of any drug is necessary in order to dose and monitor patients effectively. When used with vigilance, appropriate patient monitoring, and slow, careful titration to desired effect, midazolam is an extremely useful and safe medication for both inpatients and outpatients. PMID- 2921766 TI - Introduction to quantitative research and analysis. AB - We have now gained appreciation for both qualitative and quantitative research. Whichever method we choose can only serve to strengthen our professional identity. It has been said that qualitative research attempts to uncover what needs to be learned while quantitative research seeks to determine the amount. My advice to all PACU nurses is to begin recording observations and keep an inventory. The design of a study can be determined later; it's the research question that bears merit. Above all, do not ever discount a feeling, a hunch, or an instinct. You may well be on the verge of a very important discovery. Carpe diem--or seize the opportunity--it's worth taking! PMID- 2921767 TI - Commission questions existence of RN shortage. PMID- 2921768 TI - Isomeric yohimbine alkaloids block calcium-activated K+ channels in medullary thick ascending limb cells of rabbit kidney. AB - The alpha2-adrenergic antagonist yohimbine (YOH) and the closely related isomers corynanthine (COR) and rauwolscine (RAU) caused brief interruptions in current characteristic of a fast blocker Ca2+-activated K+ channels in cultured medullary thick ascending limb (MTAL) cells. The apparent dissociation constants (Kapp) for COR, YOH, and RAU, respectively, at the intracellular face of the channel in the presence of 200 mM K+ are 45 +/- 1, 98 +/- 2, and 310 +/- 33 microM. The Kapp for COR on the extracellular side also in the presence of 200 mM K+ was much greater at 1.6 +/- 0.17 mM. Increasing K+ on the same side as the blocker relieves the blocking reaction. The Kapp for the alkaloids varies with K+ in a manner quantitatively consistent with K+ and the alkaloids competing for a common binding site. Finally, blocking by the charged form of these alkaloids is voltage dependent with changes in Kapp of 86 +/- 7 and 94 +/- 6 microM per e-fold change in voltage for blockers applied either from the inside or outside. The alkaloids block at an electrical distance similar to tetraethylammonium, suggesting that the site within the channel pore of these molecules may be similar. PMID- 2921769 TI - Sodium D-glucose cotransport in the gill of marine mussels: studies with intact tissue and brush-border membrane vesicles. AB - Glucose transport was studied in marine mussels of the genus Mytilus. Initial observations, with intact animals and isolated gills, indicated that net uptake of glucose occurred in mussels by a carrier-mediated, Na+-sensitive process. Subsequent studies included use of brush-border membrane vesicles (BBMV) in order to characterize this transport in greater detail. The highest activity of Na+ dependent glucose transport was found in the brush-border membrane fractions used in this study, while basal-lateral membrane fractions contained the highest specific binding of ouabain. Glucose uptake into BBMV showed specificity for Na+, and concentrative glucose transport was observed in the presence of an inwardly directed Na+ gradient. There was a single saturable pathway for glucose uptake, with an apparent Kt of 3 microM in BBMV and 9 microM in intact gills. The kinetics of Na+ activation of glucose uptake were sigmoidal, with apparent Hill coefficients of 1.5 in BBMV and 1.2 in isolated gills, indicating that more than one Na+ may be involved in the transport of each glucose. Harmaline inhibited glucose transport in mussel BBMV with a Ki of 44 microM. The uptake of glucose was electrogenic and stimulated by an inside-negative membrane potential. The substrate specificity in intact gills and BBMV resembled that of Na+-glucose cotransporters in other systems; D-glucose and alpha-methyl glucopyranoside were the most effective inhibitors of Na+-glucose transport, D-galactose was intermediate in its inhibition, and there was little or no effect of L-glucose, D fructose, 2-deoxy-glucose, or 3-O-methyl glucose. Phlorizin was an effective inhibitor of Na+-glucose uptake, with an apparent Ki of 154 nM in BBMV and 21 nM in intact gills. While the qualitative characteristics of glucose transport in the mussel gill were similar to those in other epithelia, the quantitative characteristics of this process reflect adaptation to the seawater environment of this animal. PMID- 2921770 TI - Lungs of the gecko Rhacodactylus leachianus (Reptilia: Gekkonidae): a correlative gross anatomical and light and electron microscopic study. AB - The lungs of the New Caldeonian gecko Rhacodactylus leachianus were examined by means of gross dissection and light and electron microscopy. This tropical species, which is the largest living gecko, possesses two simple, single chambered lungs. Right and left lungs are of similar size and shape. The lung volume (27.2 ml.100 g-1) is similar to that of the tokay (Gekko gecko) but differs in that the gas exchange tissue is approximately homogeneously distributed, and the parenchymal units (ediculae) are very large, approximately 2 mm in diameter. The parenchymal depth varies according to the location in the lung, being deepest near the middle of the lung and shallowest caudally. Scanning and transmission electron microscopy reveal an unusual distribution of ciliated cells in patches on the edicular walls as well as on the trabeculae. Secretory cells are very numerous, particularly in the bronchial epithelium, where they greatly outnumber the ciliated cells. The secretory cells form a morphological continuum characterized by small secretory droplets apically and large vacuoles basally. This continuum includes cells resembling type II pneumocytes but which are devoid of lamellar bodies. Type I pneumocytes similar to those of other reptiles cover the respiratory capillaries, where they form a thin, air-blood barrier together with the capillary endothelial cells and the fused basement laminae. The innervation, musculature, and vascular distribution in R. leachianus are also characterized. Apparent simplification of the lungs in this taxon may be related to features of its sluggish habits, whereas peculiarities of cell and tissue composition may reflect demands of its mesic habitat. PMID- 2921771 TI - Extracellular matrix of sea urchin and other marine invertebrate embryos. AB - The extracellular matrix surrounding the sea urchin embryo (outer ECM) contains fibers and granules of various sizes which are organized in recognizable patterns as shown by ultrastructural studies, particularly stereoimaging techniques. The use of the ruthenium red method for retaining and staining the ECM, with modifications of the Luft (Anatomical Record 171:347-368, 1971) method for invertebrate embryos, allows for the clarification of certain structures, particularly fiber compaction in the interzonal region, and microvillus associated bodies. The inner ECM in the sea urchin embryo includes the basal lamina and blastocoel matrix. Stereoimages show that the fibers which are loosely distributed in the blastocoel matrix become compacted around the periphery of the blastocoel to form the basal lamina. The ruthenium red method was also used on a number of marine invertebrate embryos and larvae, representing different phyla, to facilitate comparisons between their surface coats. The similarities observed in the specimens shown suggest that ECMs are widely found on marine invertebrate eggs, embryos, and larvae, and that they resemble vertebrate ECMs and may, therefore, have similar functions. PMID- 2921772 TI - Skeletal muscle architecture of the rabbit hindlimb: functional implications of muscle design. AB - The muscle-fiber architecture of 29 muscles from six rabbits (Oryctolagus cuniculus) was measured in order to describe the muscular properties of this cursorial animal, which possesses several specific skeletal adaptations. Several muscles were placed into one of four functional groups: hamstrings, quadriceps, dorsiflexors, or plantarflexors, for statistical comparison of properties between groups. Antagonistic groups (i.e., hamstrings vs. quadriceps or dorsiflexors vs. plantarflexors) demonstrated significant differences in fiber length, fiber length/muscle length ratio, muscle mass, pinnation angle, and number of sarcomeres in series (P less than .02). Discriminant analysis permitted characterization of the "typical" muscle belonging to one of the four groups. The quadriceps were characterized by their large pinnation angles and low fiber length/mass ratios, suggesting a design for force production. Conversely, the hamstrings, with small pinnation angles, appeared to be designed to permit large excursions. Similar differences were observed between plantarflexors and dorsiflexors, which have architectural features that suit them for force production and excursion respectively. Although these differences were not absolute, they represented clear morphological distinctions that have functional consequences. PMID- 2921773 TI - Quality of life assessment in cancer clinical trials--it's time to catch up. PMID- 2921774 TI - Microvascular injury in pathogenesis of interferon-induced necrosis of subcutaneous tumors in mice. AB - DBA/2 mice were injected sc with cells from the highly malignant Friend erythroleukemia cell (FLC) 3Cl8 subline, which is resistant to mouse interferon alpha/beta, or with the ESb lymphoma. When interferon alpha/beta was injected intratumorally or peritumorally, tumor growth was markedly suppressed, and established vascularized tumor nodules became progressively necrotic. Tumor necrosis was of the coagulation type that usually results from deprivation of blood flow. Morphologic examination of approximately 1,000 blood vessel profiles and approximately 2,000 endothelial cells in 1-micron Epon sections of sc 3C18 FLC tumors showed that interferon treatment resulted in rapid and pronounced vascular endothelial cell damage that preceded tumor necrosis. No inflammatory cell infiltrate was observed. Our results suggest that interferon alpha/beta exerted an antitumor effect in these tumor models by damaging tumor blood vessels, causing disruption of tumor blood flow, which led to ischemic tumor necrosis. PMID- 2921775 TI - Glucocorticoid hormone effect on transplacental carcinogenesis and lung differentiation: influence of histocompatibility-2 complex. AB - In the mouse, the histocompatibility-2 (H-2) haplotype influences induction of lung and intestinal tumors by N-ethyl-N-nitrosourea (ENU) treatment of fetuses or infant mice. The differentiation of lung and intestinal epithelium is known to be regulated by glucocorticoids. We show that glucocorticoid-induced development of alveolar lung volume is H-2 influenced and that glucocorticoid treatment of fetuses also influences prenatal ENU induction of lung and intestinal tumors. These glucocorticoid effects on tumorigenesis are also H-2 influenced. The number of papillary lung tumors increased in B10 (H-2b) and decreased in B10.A (H-2a) mice. In the intestine, the number of tumors increased in H-2b females and decreased in H-2b males. In H-2a mice, the number of intestinal tumors was unchanged but their location was altered. We propose that the H-2 complex influences tumorigenesis in lung and small intestine by affecting the hormonal regulation of differentiation of target epithelial cells. PMID- 2921776 TI - Increased melphalan activity in intracranial human medulloblastoma and glioma xenografts following buthionine sulfoximine-mediated glutathione depletion. AB - In previous studies we demonstrated that administration of buthionine sulfoximine (BSO) to athymic BALB/c mice bearing intracranial human glioma xenografts resulted in highly selective depletion of glutathione in neoplastic tissue with minimal effects on contralateral normal brain tissue. In the present study we treated athymic BALB/c mice bearing intracranial human glioma (D-54 MG) or medulloblastoma (TE-671) xenografts with melphalan alone or BSO followed by melphalan. Administration of BSO depleted intracellular glutathione to 7.5% of the control level. BSO plus melphalan resulted in a significant increase in median survival over that produced by melphalan alone: 45.3% versus 26.4% in TE 671 and 69% versus 27.6% in D-54 MG. These studies justify further efforts to modulate chemotherapeutic and radiotherapeutic interventions of primary malignant brain tumors by depletion of glutathione. PMID- 2921777 TI - Differentiation between papillary and nonpapillary renal cell carcinomas by DNA analysis. AB - Recent studies have shown that the deletion of chromosome 3p or the loss of DNA sequences at 3p is generally associated with the development of renal cell carcinoma (RCC). However, chromosome analysis of some papillary RCCs suggested that this type of tumor differs genotypically from the most common nonpapillary RCCs. Therefore, by using cytogenetic and molecular genetic approaches, we examined human papillary and nonpapillary RCCs for the loss of heterozygosity or homozygosity at the short arm of chromosome 3. The constitutional heterozygosity for the DNF15S2 locus and for one allele of the c-erbA beta and the c-raf-1 proto oncogenes was lost in nonpapillary RCCs, whereas both alleles were retained in each papillary RCC analyzed. We conclude that the loss of DNA sequences at the chromosome 3p region is a genomic change occurring consistently in nonpapillary RCCs, but never occurring in papillary RCCs. PMID- 2921778 TI - Dermal absorption of the insect repellent DEET (N,N-diethyl-m-toluamide) in rats and monkeys: effect of anatomical site and multiple exposure. AB - The dermal absorption of 14C-ring-labeled DEET (N,N-diethyl-m-toluamide) applied in acetone to the skin of Sprague-Dawley rats and rhesus monkeys for 24 h was determined. Absorption in rats dosed middorsally was 36 +/- 8% with a urinary excretion half-life (t1/2) of 20 h. Both the extent and rate of absorption in monkeys were highly dependent on anatomic site, with 14 +/- 5% (t1/2 = 4 h) penetrating the forearm, 33 +/- 11% (t1/2 = 6 h) the forehead, 27 +/- 3% (t1/2 = 7 h) the dorsal forepaw, and 68 +/- 9% (t1/2 = 8 h) the ventral forepaw. Since DEET is commonly applied frequently by the same individual, the effect of multiple exposure was investigated. No significant difference (p greater than or equal to .3) was obtained either between the total percentage absorbed dermally with single (36 +/- 8%; t1/2 = 20 h) as compared with three (31 +/- 5%; t1/2 = 16 h) DEET applications at 2-h intervals to rats, or between single (14 +/- 5%; t1/2 = 4 h) as compared with three (12 +/- 1%; t1/2 = 4 h) applications at 0.5-h intervals to monkey forearm. A DEET metabolite detected in urine 4 h following topical exposure in humans was extractable following either acid (HCl) hydrolysis or urine treatment with beta-glucuronidase and was identified as ethyltoluamide (parent ion 163; base ion 119) following HPLC purification and characterization by GC/MS. PMID- 2921779 TI - Increased erythrocyte protoporphyrins and blood lead--a pilot study of childhood growth patterns. AB - The National Health and Nutrition Survey 1976-1980 demonstrated the inverse association of blood lead 8-35 micrograms/dl (0.4-1.7 microM) with height and weight in 2680 children 1-7 yr old. Growth has not been examined. A retrospective pilot study was made of growth, 0-42 mo, for 54 children found to have erythrocyte protoporphyrins greater than 35 micrograms/dl (0.6 mM) at 12-23 mo. For 24/54, all blood leads were less than 30 micrograms/dl (1.2 microM), with a peak annual mean of 18.5 micrograms/dl (0.9 microM); for 30/54, mean blood lead was 46.7 micrograms/dl (2.2 microM) at 12-23 mo with all subsequent blood leads greater than or equal to 30 micrograms/dl (1.2 microM). In both groups the mean height and weight at birth were at the 25th percentile. The high-lead children had increased weight velocity at 15 mo of age and were heavier at 24 mo. Weight gain related to total caloric intake, supporting food consumption, and hand-to mouth behavior as significant factors in an increased blood lead ages 9-24 mo. The monthly directional change of height and weight percentiles after 24 mo, however, showed a decreased frequency of upward shifts when blood lead was greater than or equal to 30 micrograms/dl. Although an early high food intake appears to contribute to high blood lead by increasing the intake of lead from food and mouthing, persistent increases in the high blood lead and erythrocyte protoporphyrins were associated with subsequent growth retardation. PMID- 2921780 TI - Changes in pulmonary lavage fluid of guinea pigs exposed to ultrafine zinc oxide with adsorbed sulfuric acid. AB - Ultrafine metal oxide particles (diameters less than 0.1 microns) and sulfur dioxide are important products of coal combustion. Interaction of these products in the effluent stream results in formation of ultrafine particles with adsorbed sulfur compounds, including sulfuric acid. The toxicity of ultrafine zinc oxide particles with adsorbed sulfuric acid was evaluated by comparing pulmonary lavage fluid from guinea pigs exposed for 1, 2, 3, 4, or 5 consecutive daily 3-h periods to ultrafine zinc oxide generated in the presence of sulfur dioxide (ZnO + SO2) to pulmonary lavage fluid from guinea pigs exposed to an equivalent concentration of ultrafine ZnO. Two groups of guinea pigs exposed either to SO2 or to particle free furnace gas served as additional controls. Cells, protein, and activities of lactate dehydrogenase, acid phosphatase, and alkaline phosphatase were increased in lavage fluid obtained from guinea pigs exposed to ZnO + SO2 as compared to guinea pigs exposed to ZnO. These results demonstrate the potential importance of ultrafine metal oxides as carries of sulfuric acid derived from fossil fuel combustion. PMID- 2921781 TI - Cochlear implants: update of the program at the University of British Columbia. AB - Since 1982, we have performed 26 cochlear implants at the University of British Columbia. The first 14 patients were implanted with the House/3M single-channel unit and the last 12 have been implanted with the Nucleus 22-channel unit. This paper reviews the methods used in patient selection and rehabilitation and compares the results obtained in patients using a single-channel with those using a multi-channel unit. PMID- 2921782 TI - Cochlear implant hearing performance at the University of Minnesota. AB - The hearing performance of six post-lingually deaf adults implanted with the Nucleus 22-channel device are presented. All patients achieved measurable open set speech recognition with implant alone. The best hearing performance was achieved with a combination of lipreading and cochlear implant. For this condition our group achieved an average open set speech discrimination score of 85% (CID sentences) and an average speech tracking rate of 70 words per minute. We attribute the success of our group to careful pre-operative selection, including attention to candidate motivation toward hearing rehabilitation. PMID- 2921783 TI - Analogue signal representation in the medial superior olive of the cat. AB - Temporal sound processing is likely to depend upon a delay line at a low level in the auditory pathways. We searched for such a delay line in the medial superior olivary nucleus of anesthetized cats. A remarkably pure sinusoidal neurophonic field potential could be recorded in the center of the MSO which was localized electrophysiologically as the point of the field potential polarity reversal and histologically by microinjection WGA-HRP through the recording microelectrode. Fourier analysis of the neurophonic potentials revealed increasing degradation by distortion products with distance from the MSO center. Neurophonic tuning curves indicated a similar frequency selectivity for individual recording sites as predicted by cochlear filter functions. Cross correlation of neurophonics recorded at different positions along the medio-lateral axis demonstrated the presence of a delay line, extending to over 0.6 ms. It is concluded that delay lines required for directional hearing and complex tone identification exist in the MSO. PMID- 2921784 TI - Reconstruction of intermediate sized mucosal defects with the pectoralis major myofascial flap. AB - An uncovered pectoralis major muscle flap (PMF) was utilized in 12 patients for reconstruction of mucosal defects of intermediate size. The PMF is nonhair bearing and thinner and more flexible than the myocutaneous flap. Epithelialization of the PMF occurs slowly but results in a mucosal surface that is nonkeratinized and closely resembles normal. The paddle of the PMF contracts as much as 75% during healing. However, none of our patients developed deficits attributable to contracture of the flap, presumably because only modest-sized defects were repaired. The PMF is useful for reconstruction of intermediate-sized defects approximately 6 x 6 cm, defects that are too large to close with local flaps and tend to be too small to be closed conveniently with a bulky myocutaneous flap. Contracture of the PMF precludes its use for reconstruction of large defects. PMID- 2921785 TI - [Snoring: physiopathology, surgical treatment and a modified uvulo-palato pharyngoplasty]. AB - Sleep apnea, now recognized as a specific clinicopathological entity, had received little attention until late 1960 when described by Gastaud. Since that time, following the works of Ikematsu, Guillemineault and Fujita, there has been rapid extension in the knowledge and understanding of sleep problems and associated surgery. Snoring, whether part of the sleep apnea syndrome or alone, may be explained with the help of an aerodynamic model comparing the pharynx to a Starling resistance. The factors nasal obstruction, abnormal mass in the upper respiratory airways and transmural resistance are discussed in the light of this model. To modify some of the above factors, surgical techniques have been described. We feel these conventional techniques do not take into account the normal healing process of inverted double C scars. We have modified the classic technique by sectioning the palatopharyngeus muscle and used Z-plasty to close the surgical defect. This is followed by a limited resection of the soft palate. As a consequence, the soft palate is being brought forward in the healing process and the oropharynx AP diameter is enlarged. This minimal type of resection of the soft palate precludes complications of velopharyngeal incompetency or relative pharyngeal stenosis. We have studied 200 snorers and operated on 90 of them, 25 according to the standard technique and 65 with the modified technique. The modified technique, while limiting the amount of palate to be removed and also the morbidity, is easy to standardize and offers as good results with fewer risks. PMID- 2921786 TI - Congenital cholesteatoma of the middle ear in children. AB - Congenital cholesteatoma, once considered to be a rarity, has shown an exponential increase in its incidence as evidenced by numerous clinical studies over the past decade. No explanation has been offered for this phenomenon. A review of the literature indicates that the definition of "congenital cholesteatoma" has strayed from the original one formulated by Derlacki and Clemis, which included a cholesteatoma medial to an intact tympanic membrane, without prior history of aural infections. Allowing patients with recurrent otitis media into studies may have contributed to a "false positive" rise in the incidence of this condition. This article reviews 19 cases of cholesteatomas behind intact tympanic membranes, treated at the Montreal Children's Hospital over a 10-year period. They represent 22% of the entire cholesteatoma population. There appears to be two groups of patients, each with a distinct clinical presentation that correlates well with the surgical outcome. Whether this implies different pathogenetic mechanisms remains unclear. PMID- 2921787 TI - Treatment of tracheocutaneous fistulae in children. AB - Tracheocutaneous fistula is a frequent sequel of long-term tracheotomy in children and adults. Persistence of the tracheotomy stoma can lead to increased morbidity and mortality, especially in patients with limited pulmonary reserve. Recommendations for treatment have included both primary closure as well as excision of the fistulous tract with healing by secondary intention. Operative management and outcome of tracheocutaneous fistula performed at The Hospital For Sick Children between January 1978 and January 1988 was reviewed retrospectively. Complications of primary closure included pneumothorax, pneumomediastinum, and poor wound healing, often leading to significant patient morbidity. Excision of the fistulous tract and temporary replacement of the tracheotomy tube with secondary wound healing resulted in no complications and successful closure in all cases. In our experience, tracheocutaneous fistula in the pediatric population are best managed in this way. PMID- 2921788 TI - Radical neck dissection: a subjective and objective evaluation of postoperative disability. AB - Nearly all patients who undergo radical neck dissection note significant morbidity if the XIth cranial nerve is sacrificed. Physicians can be misled to believe in a lower morbidity because the usual physical examination is unreliable in detecting weakness and because patients rarely persist in mentioning shoulder problems during follow-up visits. Eleven patients between the ages of 55 and 70, who had undergone unilateral neck dissection with sacrifice of the XIth cranial nerve, were given questionnaires and were objectively evaluated for strength and active range of motion on a Cybex II dynamometer. Eighty-two percent of patients experienced pain, 91% experienced weakness, and 91% experienced impairment on the affected side. Peak torque for the affected side ranged between 0 to 85% of the peak torque for the normal shoulder. Gravity-free active range of motions were 20 degrees to 162 degrees with 8 of 11 at 100 degrees or less. In all but two patients, the passive range of motion was limited by pain. PMID- 2921789 TI - Will the increased military low-level flying activity in Labrador be detrimental to the hearing of humans in the region? AB - The Government of Canada has directed the Department of National Defence to encourage our NATO allies to increase use of their facilities at Goose Bay, Labrador. This has already resulted in a substantial increase in the amount of military flying in the area, and more is projected. Much of the flying is done at very low altitude. The aboriginal people in the region (the Innu and, to a lesser extent, the Inuit) are demanding a halt to low-level military flying, and their representatives claim that the noise from the low-flying jet aircraft can cause hearing loss and ear disease. A survey on the ground in the area measured noise levels up to 127.7 dBA with very brief exposure levels. A task force commission to look at the problem concluded that occasionally low-level subsonic overflights might produce noise levels that were potentially damaging to hearing, but that the probability of this happening is at present very low because of the low frequency of flights. This might change if the frequency of flights increases. PMID- 2921790 TI - The "exploding" syringe. PMID- 2921791 TI - Posterolateral exposure for renal artery reconstruction. AB - Anterior approaches to the renal arteries are complicated by the intervening renal veins, inferior vena cava, and abdominal viscera. We describe techniques of direct posterolateral access to both right and left renal arteries by use of an extended retroperitoneal exposure. This approach allows for grafting from the aorta or iliac artery on either side and is particularly suitable on the left side for direct retropancreatic splenorenal artery anastomosis, which is described in detail. It is also useful for distal reconstruction of branch renal arteries, renal artery embolectomy, and autotransplantation "bench surgery." We have used this approach in 28 patients with no operative deaths and two reconstructive occlusions. PMID- 2921792 TI - Salvage of occluded arterial bypass grafts by means of thrombolysis. AB - Seventy-two thrombosed peripheral arterial bypass grafts in 62 patients were treated by local intraarterial thrombolytic infusion. The initial success rate was 69% (50 of 72 grafts). Graft material and location had no significant effect on the initial results. Urokinase was used in 43 cases with a 84% success rate, and streptokinase was used in 29 cases with a 48% success rate. After a follow-up period that ranged from 2 to 58 months, 27 grafts remained patent, with an average patency duration of 15 months (median 8 months). Overall graft patency at the end of 1 year was 60% applying life-table analysis. Factors that were evaluated to determine their effect on long-term patency included graft age and material, graft location, and the presence or absence of an underlying correctable lesion. The most significant factor in long-term patency was the presence of a lesion that was correctable by surgical revision or balloon angioplasty. In 25 grafts with underlying stenotic lesions, the 1-year patency was 86% after successful treatment. Twenty-five grafts without detectable lesions had 37% 1-year patency. PMID- 2921793 TI - Clinical and chemical characterization of an adventitial popliteal cyst. AB - We present further evidence that adventitial cysts of the popliteal artery are ganglions, based on studies of a lesion found in a 51-year-old man. The cyst was located entirely within the adventitia, lacked a cellular lining, and did not communicate with either the arterial lumen or the synovial space. The contents were gel-like and composed of 1.64 gm of hyaluronic acid and 0.20 gm of protein per dl. This material did not possess boundary-lubricating ability in a test system that slides natural latex rubber against glass. The histologic appearance, chemical composition, and absence of lubricating ability more closely resemble the characteristics of ganglions. These findings suggest that the cyst was not synovial but rather ganglionic in origin. PMID- 2921794 TI - Cerebrovascular accident after Greenfield filter placement for paradoxical embolism. AB - A 69-year-old man with paradoxical embolism suffered a cerebral embolism despite treatment with anticoagulants and placement of a Greenfield filter. The open architecture of the filter allows it to maintain caval patency better than other mechanical devices, but this design also permits passage of emboli up to 3 mm in diameter. Although such small emboli do not produce symptoms in the pulmonary circuit, they can be devastating in the cerebral circulation. For this reason, the Greenfield filter may be inadequate treatment for paradoxical embolism. Ligation of the inferior vena cava is proposed as an alternative that provides better protection against small emboli. PMID- 2921795 TI - Vascular prosthetic infection with Staphylococcus epidermidis: experimental study of pathogenesis and therapy. AB - To determine whether a slime-producing strain of Staphylococcus epidermidis was capable of producing acute infection of a prosthetic vascular graft, 5 cm segments of knitted Dacron were implanted in the infrarenal aortic position of dogs in three groups of animals. These included a control group (no graft contamination), a contaminated group that received a graft soaked in an S. epidermidis solution (untreated group), and a contaminated group in which perioperative antibiotics (three doses of cefamandole, 100 mg/kg) were administered (prophylaxis group). In all the animals reexploration and graft removal were performed at 10 days, with replacement of the defect being achieved with a new uncontaminated graft. These animals underwent exploration a third time after an additional 10-day period. S. epidermidis was not grown from the control animals (n = 7) but was cultured in 44% of the prophylaxis group (n = 9) and 88% of the untreated group (n = 16) during at least one of the operative procedures (chi 2 = 15.859; p less than 0.001). The pathologic features of acute S. epidermidis infection were best seen in the untreated animals and included anastomotic disruption (56%), periaortic hematoma, and lymphadenopathy (94%). Microscopic examination of the aortic tissues revealed extensive infiltrates of leukocytes, macrophages, and foreign body giant cells with aortic necrosis. These features were less prominent in the prophylaxis animals. We conclude that S. epidermidis is capable of producing acute graft infection with perigraft inflammation and anastomotic disruption. The administration of perioperative antibiotics reduced but did not abolish these effects of bacterial contamination of prosthetic vascular grafts. PMID- 2921796 TI - Rotational muscle flaps: a new technique for covering infected vascular grafts. AB - Twenty-one patients with established localized infection of vascular bypass grafts were treated with aggressive debridement and rotational muscle flap coverage to control graft infection. There were six gram-positive, six gram negative, four mixed, and three fungal graft infections. Graft material included Dacron, Gore-Tex (registered trademark of W. L. Gore Associates Inc., Elkton, Md.), Dacron and Gore-Tex in combination, and saphenous vein. Twenty of 21 patients had successful preservation of graft function, local wound healing, and control of infection. There were no amputations or deaths. The one failure was caused by incomplete debridement of an infected graft segment. Aggressive debridement and rotational muscle flap coverage is an effective means of treating locally infected vascular bypass grafts. PMID- 2921797 TI - Technical innovations in nonreversed translocated saphenous vein bypass. PMID- 2921798 TI - Exposed subcutaneous vein graft in the calf: coverage by conversion to a deep anatomic position. PMID- 2921799 TI - Does compliance mismatch alone cause neointimal hyperplasia? PMID- 2921800 TI - A prospective randomized trial of Unna's boots versus hydroactive dressing in the treatment of venous stasis ulcer. PMID- 2921801 TI - Alterations in aortic endothelial cell morphology and cytoskeletal protein synthesis during cyclic tensional deformation. PMID- 2921802 TI - [A case of vesical carcinoma with sarcomatous changes--immunohistochemical and electron microscopic observations]. AB - The immunohistochemical and electron microscopic characteristics of a vesical carcinoma with a sarcomatous change in a 90-year-old man are described. Keratin was strongly positive in the carcinomatous region and was also identified in the sarcomatous region. CEA was present only in the carcinomatous region. Both the carcinomatous and sarcomatous regions were negative for S 100 protein, myoglobin, lysozyme, and desmin. Electron microscopically, a few tumor cells with tonofilaments were observed in the sarcomatous region. Many tumor cells in the sarcomatous region had no characteristic structures suggestive of epithelial or mesenchymal origin. However, transitional types of tumor cells, between the epithelial cells and the cells with neither epithelial nor mesenchymal differentiation, were noticed. Therefore, this suggested that the sarcomatous region was a site of immature epithelial cell proliferation. PMID- 2921803 TI - [A case of spermatocytic seminoma]. AB - In April, 1987, we treated a 33-year-old male patient who presented a painless swelling of the right scrotal content of 6 months duration. After surgery, the resected testis weighed 130 g, and the cut surface showed an edematous, white yellow, homogenous tumor. A histopathological examination revealed a typical spermatocytic seminoma composed of three types of tumor cells. The small cells had pyknotic nuclei and an eosinophilic cytoplasm while the medium-sized cells and most of the giant cells had nuclei containing granular chromatins. Some of giant cells contained a filamentous, chromatin-like spireme of primary spermatocytes. A chest X-ray, CT scanning and lymphography revealed no metastatic lesions, and the patient is still alive with no evidence of disease 10 months after the orchiectomy. PMID- 2921804 TI - [Diagnosing the depth of esophageal carcinoma invasion by esophagography scoring]. AB - In patients with an esophageal carcinoma, it was important to determine the depth of the carcinomatous involvement so as to decide on its resectability and prognosis. Thus four measurements of the esophagography findings involving ninety five post-esophagectomy patients were categorized into four grades and scored from point 1 to point 4, depending on the degree of severity, the measurements being the size of the tumor, the circumferential carcinomatous invasion, the degree of stenosis, and the depth of the ulcer. The sum total scores of these four esophagography findings were found to correlate well (P less than 0.01) with the depth of the invasion (submucosa, muscularis propria, adventitia, and the adjacent structures). PMID- 2921805 TI - [The prognostic significance of esophageal carcinoma based on various irradiation methods]. AB - From 1975 to 1987, 170 unresectable esophageal carcinomas were curatively irradiated. Ninety-eight cases were treated with conventional fractionation and a small field, 32 cases to a large T-shaped field, and 40 cases with conventional 50-60 Gy doses followed by 14-28 Gy of low-dose rate telecobalt therapy (LDRT: 1 Gy/hr, 4-7 Gy/day). The one-year, three-year and five-year survival rates in all cases were, 33%, 9% and 5%, and in LDRT groups, 37%, 15% and 8%, respectively. The survival rate and the local cure rate in the LDRT group were a little better than the others. The prognosis of T-shape group was proven to be the same as conventional group. PMID- 2921806 TI - [DNA analysis by flow cytometry in breast carcinoma]. AB - Using deparaffinized tumor specimens, a flow cytometric DNA analysis was performed in 63 primary breast cancers from patients who were treated from 1976 through 1982. Fourty-three percent of the cases were found to be aneuploid, and 57% were diploid. No trend to increased aneuploid proportion with a more advanced disease was noted. There was no correlation between the level of ploidy and the clinicopathological factors. Aneuploid tumors seem to have a poorer survival, but no significant difference was found between the two patterns of ploidy. Patients with a low S-phase fraction (SPF) had a significantly longer survival than those with a high SPF. A DNA analysis of the tumor cells in breast cancer is felt to be use for a prognostic evaluation. PMID- 2921807 TI - [A case-control study of stomach cancer in young females, with special reference to the effects of pregnancy and delivery]. AB - To investigate the effects of pregnancy and delivery on stomach carcinogenesis, we have conducted a case-control study. The cases consisted of females aged 34 or below who had been histologically diagnosed as having a stomach cancer, covering a period from 1967 to 1986 at the Center for Adult Diseases, Osaka. Our birth year-matched controls were selected from female examinees who had undergone a gastroendoscopy in 1986. In this manner, a total of 79 cases and 158 controls were obtained. For women in the age group from 30 to 34, a history of their pregnancies and deliveries seemed to have protective effects on stomach carcinogenesis (RR = 0.36, P less than 0.05), whereas for those in the age group under 30, it appeared to be a risk factor for stage IV stomach cancer (RR = 4.42, P less than 0.05). PMID- 2921808 TI - [Dysplasia of the gallbladder]. AB - Out of 2,027 resected gallbladders that were examined, 46 (2.2%) manifested dysplasia and, to study this further, step sections, 5 mm apart, were performed. The average age of these dysplastic cases was 63.8 years, with a male to female ratio of 1:3. The most frequent dysplastic sites in the gallbladder were in the fundus and the body. Excluding adenomas, polypoid lesions, the dysplasia appeared flat, granular, or irregular. As to diameter, 68.6% were within 1 cm, and 89% were no more than 2 cm. The majority of cases manifesting mild dysplasia had lesions of up to 5 mm in size while the lesions seen in moderate cases were within 2 cm. Stones were found in 80.4% of the cases, and incidences of intestinal metaplasia and pseudopyloric gland metaplasia were found in 80.4% and 100% of these cases, respectively. Incidences of dysplasia adjacent to the carcinoma was seen in 41.8% of the cases, and frequently found in early-stage lesions and well-differentiated carcinomas. Our findings have led us to believe that recognition of the intestinal metaplasia-dysplasia-carcinoma sequence is important. PMID- 2921809 TI - [A clinicopathological study of advanced ovarian cancers without an enlargement of the ovaries]. AB - A clinicopathologic study of advanced ovarian carcinomas without an enlargement of the primary site has been performed. Cases studied were taken from 64 cases with a "common" epithelial tumor whose ovaries upon resection were directly measured for size. The ovaries of five cases (8%) were normal in size, and 3 (5%) of this number had been treated by chemotherapy prior to the resection of their ovaries. All three cases had been suspected to have an ovarian cancer at the start of treatment, one of these cases given a definite diagnosis of ovarian cancer, stage III, and the remaining two cases diagnosed as belonging to a special category. In these 3 cases, the ovaries had decreased in size and the primary cancerous site was difficult to determine, owing to the administered chemotherapy. A preoperative diagnosis of the remaining two of the 2 cases suspected an ovarian cancer in one, and a uterine corpus carcinoma, Ia in the other, associated with an ovarian cancer, stage III. These findings suggest that even though the enlargement of the ovaries was not to be remarkable, a laparotomy should be performed in cases strongly suspected of ovarian cancer, so as to ascertain the correct diagnosis by a careful inspection of the intraabdominal cavity, such as checking for the presence of ascites with malignant cells, or an elevated serum CA 125 without any other accountable primary foci. PMID- 2921810 TI - [Effect of morphine in cancer pain]. AB - The usefulness of oral morphine to alleviate pain has been tested in 70 patients with cancer. The efficacy was found to be 87% (61/70). The starting dose was 10 mg/d-12 mg/d (mean 36 mg/d), and the maximum dose was 10 mg/d-3,600 mg/d. Twenty four of these patients were able to stay at home or go to the hospital for dose treatment. In 27 patients, oral morphine dose were able to administrated until death. Although vomiting and constipation were frequent side effects, the administration of adjuvant drugs relieved these symptoms. It was found that these oral morphine doses did not shorten a patient's life span. Thus we have concluded that oral morphine proved a useful, safe, and convenient drug for the control of cancer pain. PMID- 2921811 TI - [A case of esophageal carcinoma complicated by Crohn's disease]. AB - A case of an esophageal cancer complicated by Crohn's disease is reported. A 76 year-old female was admitted to the Nara National Hospital with symptoms of melena and dysphagia. An esophageal X-ray study revealed a circular, stenotic lesion at the lower intra-thoracic esophagus. Histological examination of a specimen confirmed a moderately differentiated squamous cell carcinoma. A barium enema was then given which showed an irregular stenotic lesion, 28 cm in length, at the terminus of the ileum. Thus, an esophageal blind resection and a resection of the terminal portion of the ileum was jointly performed. A histological examination of the resected ileum confirmed Crohn's disease. PMID- 2921812 TI - [An autopsied case of idiopathic interstitial pneumonia, showing a remarkably elevated serum level of CA 19-9]. AB - Discussed herein is an autopsied case of a 30-year-old male with Idiopathic Interstitial Pneumonia (IIP) manifesting a markedly elevated CA 19-9 in the serum (maximum, over 120,000 U/ml). Despite a careful examination, no malignant lesion was found. The postmortem examination revealed a marked elevation of CA 19-9 in the serum and in the lung tissue. Further immunohistochemically regenerative bronchiolar and alveolar epithelial cells were more intensely positive for CA 19 9 than in our controls. These CA 19-9 positive cells for the most part, were found to stain with alcian blue. It is considered that IIP induces activation of sialyl-transferase in these cells. PMID- 2921813 TI - [A case of tubular adenoma of the breast preoperatively suspected to be an advanced cancer]. AB - A very rare case of a tubular adenoma of the breast is reported. The patient, 59 year-old woman, was admitted to hospital because of a large, left breast tumor. The tumor, 11 cm in diameter, was adhered to the surface skin. Because a malignancy was suspected, an incisional biopsy was first carried out. A pathologic examination revealed it to be a tubular adenoma, and a simple mastectomy was chosen as the operative procedure because a latent malignancy was not ruled out. The removed tumor was grossly cystic and a histological examination supported the finding that it was a non-malignant tubular adenoma. PMID- 2921814 TI - HST1 and INT2 gene coamplification in a squamous cell carcinoma of the gallbladder. AB - The HST1 gene has previously been found to be amplified in over 40% of squamous cell carcinomas of the esophagus. We performed Southern blot analyses on squamous cell carcinomas of the lung, nasal cavity, uterine cervix and gallbladder, using HST1, INT2 and five other oncogenes as probes. The HST1 and INT2 genes, both of which were mapped to chromosome 11 at band q13, were coamplified in a squamous cell carcinoma of the gallbladder. The degree of amplification exceeded eight fold. PMID- 2921815 TI - Early lesions and natural progression of bladder carcinoma (minute bladder carcinoma). AB - Morphological analyses of minute bladder carcinomas (less than 5mm in diameter) and their natural progression to advanced carcinomas were examined. There were 71 minute carcinomas in 25 cases, the highest number in any one case being eight. The growth forms of the 71 minute carcinomas were classified into six types: papillary (35), Brunn's nest-like (20), intermediate between those two (9), simple displacing (3), inverted papillary (2) and invasive (2). There appeared to be two kinds of advanced papillary carcinoma, one forming a papillary tumor from the onset of progression, and the other, initially exhibiting Brunn's nest-like, intermediate or simple displacing tumors and finally forming papillary tumors. Some of the papillary carcinomas seemed to have developed from papillomas. Two pathways to invasive carcinomas from papillary tumor were suggested: one showing invasive growth directly from the papillary tumor, the other developing invasive changes in the proliferative processes from Brunn's nest-like or intermediate tumors. Invasive growths occurred in tumors of G2 or over and in those in which the character of the tumor was changed to that of squamous cell carcinoma. They appeared to be more frequent (four cases out of 13 compared with one out of 10) in the advanced papillary carcinomas which had seemingly developed from the various kinds of minute tumor other than papillary. Invasive minute carcinoma was regarded as being an early stage of advanced non-papillary invasive carcinoma. PMID- 2921816 TI - Acute lymphoblastic leukemia following treatment with human growth hormone in a boy with possible preanemic Fanconi's anemia. AB - The patient had a low birth weight and was born with appearance anomalies including microcephalus, microphthalmia, hypoplastic mandible, double chin due to cutaneous fold, micropenis. Ability to move and intelligence appeared to develop normally, but growth was markedly retarded. In June 1982, at the age of 2 yr 4 mo, the patient underwent tolerance tests whereby a deficiency of human growth hormone (GH) was proved by poor GH secretion response. GH was administered until April 1985 when acute lymphoblastic leukemia developed. The patient's younger brother, born in 1986, had similar birth anomalies and was diagnosed as having Fanconi's anemia. It therefore seems possible that our patient developed his acute leukemia through the stimulatory effect which GH had on a predisposition to leukemia. PMID- 2921817 TI - Control of cisplatin-induced delayed emesis with metoclopramide and dexamethasone: a randomized controlled trial. AB - Forty-two patients with advanced lung cancer undergoing chemotherapy containing cisplatin (80 mg/m2) were submitted to a randomized controlled trial to evaluate the effect of the combination of metoclopramide and dexamethasone for the treatment of delayed cisplatin-induced emesis occurring more than 24 hours after cisplatin administration. All patients received intravenously (i.v.) high-dose metoclopramide and dexamethasone on the day of cisplatin treatment. Excellent emetic control (no emesis during the 24 hours following cisplatin administration) was achieved in 30 out of 41 patients (73%) with this combination. Patients treated i.v. with metoclopramide and dexamethasone on days 2-7 experienced less delayed emesis, nausea and anorexia compared to those treated with a placebo (delayed emesis, 25 vs 50%, respectively, P = 0.105; more than four days of nausea, 10 vs 35%, respectively, P = 0.059; less than three days of anorexia, 80 vs 50%, respectively, P = 0.048). Although the results of the study showed no statistically significant advantage with the combination of i.v. metoclopramide and dexamethasone for patients treated with cisplatin, in view of the short duration of anorexia and the marginal reduction in nausea. Female patients tended to have more emetic episodes and extrapyramidal side effects (except akathisia) than male patients, but the differences were not statistically significant except for acute emesis (P less than 0.005). PMID- 2921818 TI - Cimetidine-mediated augmentation of lymphocyte responses to phytohemagglutinin in gastric cancer patients. AB - The effect of cimetidine, a histamine type 2 receptor antagonist, on lymphocyte responses to phytohemagglutinin (PHA) was studied in 58 gastric cancer patients. Cimetidine significantly enhanced lymphocyte responses to PHA in certain gastric cancer patients. The degree of enhancement was associated with tumor load. A significant inverse correlation was observed between the degree of enhancement and that of the original lymphocyte responses to PHA. The degree of enhancement significantly correlated with the proportions of OKT3 and OKT8 positive cells. A determination of the degree of enhancement in selected gastric cancer patients revealed it to fall to a low level after a certain period following curative gastric resection. These data appear to favor the in vivo therapeutic administration of cimetidine to advanced gastric cancer patients. PMID- 2921819 TI - Testicular tumors occurring in non-twin brothers: a case report. AB - The present report describes two cases of seminoma that occurred simultaneously in non-twin brothers. These siblings were typed for HLA-A, -B, -C and -DR specificities, and manifested identical haplotypes. Sixty-four sets of affected siblings have been reported prior to the present cases. We examined HLA-DR antigen in brothers with testicular tumors and hereditary roles in the etiology are discussed. PMID- 2921820 TI - [Mechanism in the development of symptoms. 1. Keypoints in observation. Fever]. PMID- 2921821 TI - [Psychological approach in nursing. 1. Negative attitude of a patient facing hysterectomy]. PMID- 2921822 TI - [Unforgettable patients in a psychiatric ward. Mr. A. who taught a lesson in interpersonal relationships]. PMID- 2921823 TI - [Experience in nursing education at an American university]. PMID- 2921824 TI - [Nursing education at universities: a view from clinical nursing]. PMID- 2921825 TI - [The role of college education in nursing]. PMID- 2921826 TI - [Expectation and results of college education]. PMID- 2921827 TI - [University nursing education and the study of nursing: a view of a student]. PMID- 2921828 TI - [In search of quality home service care closely tied to the area: an interview with Mrs. Joanne M. Pedersen, supervisor, Ramsey County Public Health Nursing Service, Minnesota]. PMID- 2921829 TI - [Communication with cancer patients on their treatment: patients' awareness of the nature of their illness at the time of chemotherapy and an analysis of their attitudes toward recovery]. PMID- 2921830 TI - [Bedside nursing. A reflection on the interactions with a psychiatric patient who developed a romantic attachment to nursing personnel]. PMID- 2921831 TI - [A profile. Ms. Kisano Shioda, a 91-year-old lady who is an active member of Akebonokai, an organization for breast cancer patients]. PMID- 2921832 TI - [An organization of breast cancer patients. 10. Encouragement by my family]. PMID- 2921833 TI - [Experience of a nursing instructor as a patient. 10. Apprehension associated with illness]. PMID- 2921834 TI - [Nursing theory 36. Orem's nursing theory. 2. The self-care theory and theory of insufficient self-care]. PMID- 2921835 TI - [Information science for nurses. 10. Information science and judgment]. PMID- 2921836 TI - [Welfare and medical care in the aging society. 29. Aging and married couples. 2]. PMID- 2921837 TI - [A report of the international cooperative medical project in Colombia. 1. Selection of a model area]. PMID- 2921838 TI - Digitalis intoxication and treatment with digoxin antibody fragments in renal failure. AB - Severe digitalis intoxication today is preferentially treated by intravenous infusion of Fab fragments of digoxin antibodies (Digitalis Antidot BM). The kinetics of Fab fragments in the circulation are well known when kidney function is normal or slightly impaired. There are no data available, however, in complete renal failure. We observed a patient with life-threatening digitalis intoxication (serum digoxin, 3.7 ng/ml) and anuria, who was treated successfully by 160 mg Fab fragments i.v. Serum digoxin and Fab fragment concentrations could be followed for 229 h. The extrarenal clearance of Fab fragments was lower (5.6 ml/min) than in patients with normal kidney function (10.9 ml/min). This finding suggests that lower doses than usual might be sufficient for treating patients with severe digitalis intoxication and renal failure. PMID- 2921839 TI - [Oxoferin and sodium chlorite--a comparison]. AB - Oxoferin, a preparation approved for wound treatment, has been subjected to an in vitro analysis. 1. Oxoferin produces methaemoglobin even if diluted 500 fold, and leads to additional alterations if added in high concentrations to red cells. Sodium chlorite (NaClO2, 15 mM) is equivalent to undiluted Oxoferin. 2. Oxoferin in fiftyfold dilution damages fibroblasts in cell culture slowly and persistently. This dilution is equieffective with a 200 microM solution of sodium chlorite. Oxoferin and sodium chlorite also damage vascular endothelial cells. 3. The oxidation equivalent of Oxyoferin is 12.3 mM sodium chlorite. Our data indicate that Oxoferin may be equated essentially with aqueous sodium chlorite. PMID- 2921841 TI - Multiple brown tumors in a patient with nutritional secondary hyperparathyroidism. AB - For years, brown tumors have been considered to be a characteristic of primary hyperparathyroidism. However, since 1963 several reports indicate the incidence of brown tumors in patients with renal secondary hyperparathyroidism to be 1.5% 1.7%. The appearance of multiple brown tumor lesions is rather uncommon in secondary hyperparathyroidism which is also true for malabsorption as its cause. We report on a 56-year-old man presenting with pain in the bones and multiple osteolyses. A bone biopsy specimen and the laboratory examinations were indicative of secondary hyperparathyroidism caused by malabsorption most likely due to Billroth's II/I gastric resection. Thus, the patient's osteolyses represent brown tumors which have been induced by nutritional secondary hyperparathyroidism. PMID- 2921840 TI - Carpal tunnel syndrome and vitamin B6. AB - Twelve patients with carpal tunnel syndrome were studied. Clinical and electrophysiological data were obtained and an estimation of vitamin B6 (pyridoxine) status by an assay of erythrocyte aspartate aminotransferase and coenzyme stimulation assay were done. None of the patients was found to have vitamin B6 deficiency. Patients were treated with 150 mg of pyridoxine daily for 3 months. Erythrocyte aspartate aminotransferase increased significantly (p less than 0.001) in all the patients. In 6 patients there were clinical and electrophysiological improvement and erythrocyte aspartate aminotransferase increased more than in the other 6 patients. The data obtained appear to indicate that although vitamin B6 deficiency is not common in carpal tunnel syndrome patients, pyridoxine supplementation can be recommended as adjuvant treatment in those patients undergoing surgery. PMID- 2921842 TI - Non-responsiveness to allopurinol in renal hypouricaemia. PMID- 2921843 TI - Correlation of caffeine elimination and Child's classification in liver cirrhosis. AB - Apparent pharmacokinetic parameters of caffeine elimination from the circulation were determined in 27 patients with histologically confirmed liver cirrhosis, 8 patients with miscellaneous liver disease, and 8 patients with other than liver disease. The usefullness of this quantitative test to assess the severity of liver cirrhosis was compared to the Child-Turcotte or Child-Pugh classification score as well as to the galactose elimination capacity of these patients. Using reversed-phase high pressure liquid chromatography caffeine, paraxanthine, theophylline, and theobromine were analysed in blood plasma collected before and after an oral dose of caffeine. Compared to apparent caffeine pharmacokinetics in patients with normal livers or miscellaneous liver disease, cirrhosis was characterized by a statistically significant reduction in apparent caffeine clearance and prolongation in half-life. The reduced apparent plasma disappearance rate of caffeine in cirrhotics was related to the retarded formation of paraxanthine which was the main metabolite of caffeine in blood plasma both in the absence or presence of liver disease. The apparent caffeine clearance in cirrhosis decreased with increasing Child-Turcotte classification score: Child's class A patients differed significantly from Child's class B or Child's class C patients, whereas the difference between Child's class B and C patients did not reach statistical significance (Wilcoxon's rank test). In addition there was a strong correlation between the Child-Pugh classification score and apparent caffeine clearance (P less than 0.001). However, no correlation existed between Child's classification and galactose elimination capacity. Our data emphasize the value of the Child-Turcotte or Child-Pugh classification in assessing the severity of liver cirrhosis in a simpler and less time-consuming way than using quantitative liver function tests. PMID- 2921844 TI - [Megakaryocytic myelosis--clinical aspects, morphology and platelet function]. AB - The study reviews 22 patients, aged between 19 to 73 years, with megakaryocytic myelosis. In the course of the disease 11 patients presented haemorrhagic manifestations, 12 patients thrombotic complications, and 6 patients the association of haemorrhage and thrombosis. The maximum platelet counts ranged from 524 to 2700 x 10(9)/l. The bone marrow showed a conspicuous megakaryocytic proliferation with polyploidy of the nuclei, giant forms and clusters. Marked alterations of erythro- and granulopoiesis were excluded. There was no evidence for a reactive thrombocytosis in any case. Patients with thrombocythaemia due to megakaryocytic myelosis (n = 14), with secondary thrombocytosis of various origin (n = 16), and a control group of healthy donors (n = 20) were investigated with respect to the aggregation behaviour and the total calcium content of blood platelets. In 9 of 14 patients with megakaryocytic myelosis platelet rich plasma did not respond to epinephrine (15 mumol/l), a concentration which induced at least weak aggregation in 14 of 16 patients with secondary thrombocytosis and also in healthy subjects. In patients with megakaryocytic myelosis the mean extent of aggregation induced by epinephrine, collagen or adenosine diphosphate was significant lower as compared to controls whereas in patients with secondary thrombocytosis in most cases this parameter did not differ significantly from that of controls. The total calcium content of platelets was significantly lower in both groups of patients as compared to controls. In 14 patients with megakaryocytic myelosis the concentration of the glycoprotein (GP) IIb-IIIa complex was estimated by crossed- and rocket-immunoelectrophoresis and found to be decreased in 8 of them.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2921845 TI - Carcinoma of the nasopharynx--comparison of the UICC and Ho clinical staging systems. AB - From 1974 to 1985 definitive radiation therapy was performed in 76 patients with nasopharyngeal carcinoma (NPC). Of the 76 patients 59 presented UICC stage IV and 13 UICC stage III. The distribution of the stages was more homogeneous for the Ho system: Ho I, n = 4; II, n = 21; III, n = 16; IV, n = 32; V, n = 3. Radiotherapy followed the guidelines of the M.D. Anderson Hospital in Houston. A median dose of 68 Gy was given to the primary and of 66 Gy to the neck nodes, independent of the histologic subtype. The 5-year actuarial survival rate was 41% and the disease specific relapse-free survival (r.f.s.) 45%. Analysis according to the UICC classification and Ho's classification showed obvious deficiencies in both staging systems, but did not result in major prognostic differences. The freedom from local relapses correlated (P less than 0.05) with the T categories of the UICC at presentation (75% in T1 vs 45% in T4) and the freedom from distant metastases was significantly influenced by the cervical status (fixed cervical lymph nodes (UICC N3) vs, e.g., UICC N2: 51% vs 90%; P less than 0.05). In case of supraclavicular lymph nodes (Ho IV; Kyoto C) the freedom of distant metastases was lower than in case of upper cervical lymph nodes (58% and 79%, respectively; P = 0.3). PMID- 2921846 TI - [Calcium-free hemodialysis--value in therapy of hypercalcemic crisis]. AB - If conservative treatment of hypercalcemic crises is ineffective, low calcium bath or zero calcium bath hemodialysis represent good alternatives. We report 5 patients (from 54 to 82 years old) treated with calcium free acetate hemodialysis because of hypercalcemic crises due to breast cancer with bone metastases, thiazids' medication and immobilisation, liver cirrhosis, hepatocellular carcinoma and hyperparathyroidism. By 3 hours' therapy calcium concentration could be reduced from a mean value of 3.74 mmol/l (3.13-4.46) to 2.47 mmol/l (1.38-3.12). In 3 cases rapid clinical improvement was achieved and in 4 cases the subsequent conservative therapy was sufficient to maintain serum calcium levels within reference range. In accordance to other investigators we consider hemodialysis as an effective method of low risk in hypercalcemic crises. Calcium rebound may occur in patients with hyperparathyrodism. PMID- 2921847 TI - [No fear of analgesics! Pain-free tumor patients]. PMID- 2921848 TI - [Shared pain]. PMID- 2921849 TI - [Position paper on anesthesia]. PMID- 2921850 TI - [Anesthesia. Use in emergency situations]. PMID- 2921851 TI - [Revision of guidelines. Current status of nursing education]. PMID- 2921852 TI - [Nursing teachers in conflict]. PMID- 2921853 TI - [Educational evaluation in the nursing facility--a precious tool]. PMID- 2921854 TI - [Almost like home]. PMID- 2921855 TI - [A new program at Bon Secours. 3 post-diploma specialties, one purpose]. PMID- 2921856 TI - [Prevention of mouth disorders in terminal patients. The importance of nursing diagnosis]. PMID- 2921857 TI - [Physician-patient: the dilemma of truth. 1]. PMID- 2921858 TI - Bone marrow embolism following cryosurgery of bone: an experimental study. AB - Cryosurgery is commonly used in medicine for treatment of benign and malignant lesions. We had clinical and experimental data indicating that cryosurgery of intact bone could cause bone marrow intravasation and embolism, i.e., particles of bone marrow entering extraosseous veins and occluding pulmonary vasculature. This study was designed to investigate the pathogenesis of bone marrow intravasation and embolism after cryosurgery. Three hypotheses on the pathogenesis of bone marrow intravasation were tested using a model of cryosurgical continuity lesion in rats and rabbits. Influence of physical and circulatory factors were excluded supporting a mechanical-biological hypothesis; the intravasation of bone marrow after cryosurgery of bone is caused by an increased intramedullary pressure. The increased intramedullary pressure is due to edema in the medullary cavity caused by cryosurgical damage to cell membranes. It is demonstrated that the bone marrow intravasates can embolize to the lungs causing respiratory insufficiency. This can be a serious complication following cryosurgery of intact bone. Prophylactic decompression of the medullary cavity can possibly prevent the rise in intramedullary pressure and thus intravasation and embolisation of bone marrow after cryosurgery of intact bone. PMID- 2921859 TI - An artificial anal sphincter. Phase 2: Implantable sphincter with a perineal colostomy. AB - To find an alternative to the stigmata of abdominal colostomy, an artificial anal sphincter (utilizing the currently available artificial urinary sphincter) was implanted around an end perineal colostomy following standard abdominal perineal resection. Of 13 swine, 7 completed full evaluation with working sphincters, 3 animals died prematurely of unrelated causes, and 3 animals were sacrificed due to sphincter slough before inflation was begun. Seven animals had long-term evaluation of the sphincter for 2 to 6 months' duration. In 5 animals (72%) there was complete fecal continence; one animal (14%) had occasional partial incontinence and one had total incontinence, both due to sphincter malfunction from breakage of the connecting tab. Two of the seven animals had delayed slough of the sphincter after 2 months and 4.5 months of success, and 2 animals had erosion of the intraperitoneal balloon reservoir into the small bowel. In addition, 5 of 9 (55%) control pumps were complicated by skin erosion or infection; all were relocated successfully. The fact that an intact artificial anal sphincter can provide excellent continence demonstrates that this concept of perineal placement for bowel control is valid. Refinements in the device to prevent tab breakage, investigation of correct sphincter pressures to prevent sloughing, and better sites for implantation of the pump and balloon reservoir are requisite solutions for a fully implantable system to restore near-normal bowel function after radical abdominal perineal resection. PMID- 2921860 TI - Systolic time intervals in canine experimental acute hemorrhagic pancreatitis. AB - The effect of experimental acute hemorrhagic pancreatitis on hemodynamics and systolic time intervals were studied simultaneously by catheterization in dogs. Following the initial hemodynamic measurements pancreatitis was induced by a mixture of trypsin and sodium taurocholate infused into the pancreatic duct (PG, n = 7). After 60 min of surveillance the hemodynamic measurements were repeated and the results were compared to those obtained from the sham-operated group (CG, n = 7) paced at a similar contraction frequency to the PG after the follow-up time. Left ventricular ejection time (LVET) and the ratio of PEP/LVET (PEP, preejection period) increased more in the PG than in the CG (P less than 0.05 and P less than 0.001, respectively). This was related to a lower left ventricular end-diastolic volume and pressure in the PG in comparison to the CG (P less than 0.05). PEP remained unaltered in both groups during the interventions. No significant differences between the groups were observed in the responses of the maximum value of the left ventricular systolic pressure rise (dP/dtmax). The ejection fraction decreased more in the PG than in the CG (P less than 0.05), which was related to the decreased end-diastolic volume in the PG (P less than 0.001). Mean aortic pressure decreased significantly in the PG (P less than 0.01). The results indicate that experimental acute hemorrhagic pancreatitis leads to altered loading conditions of the heart and causes marked alterations in the systolic phases of the contraction cycle. This model of experimental pancreatitis does not depress the myocardial contractility on the basis of these results. PMID- 2921861 TI - Effects of enteral and intravenous antimicrobial treatment on survival following intestinal ischemia in rats. AB - One hundred and twenty rats underwent transection of the superior mesenteric artery. The animals were randomly divided into eight groups of 15 animals. Control group 1 and groups 3, 5, and 7 received intravenous normal saline, gentamicin, metronidazole, and gentamicin plus metronidazole, respectively. Control group 2 and groups 4, 6, and 8 received the same compounds enterally. Small and large bowel sections were taken postmortem and a necrosis score was assigned in blinded fashion. Gentamicin did not prolong survival, indicating that gram-negative microbes were not important in this pathology. Longer survival times for animals given either metronidazole or gentamicin plus metronidazole (P less than 0.01) indicate that anaerobes were a causative factor in mortality. During the first 15 hr after ischemia, antibiotics did not change mortality. After 15 hr, enteral administration was superior to intravenous administration in any regimen including metronidazole (P less than 0.01). PMID- 2921862 TI - Continuous intravenous ammonia infusion as a model for the study of hepatic encephalopathy in rabbits. AB - To obtain a more precise pathophysiological evaluation of the role of ammonia in acute hepatic encephalopathy, we compared the plasma ammonia concentrations and electroencephalographic recordings (EEGs) of rabbits with surgically induced acute hepatic failure (AHF, n = 10) and normal rabbits administered an infusion of ammonium acetate (NH4-Ac, n = 7) over a 10-hr period. AHF was surgically induced by portocaval shunting followed by hepatic artery ligation 48 hr later. In the infusion group the dose of NH4-Ac, initially 0.78 mmol/kg/hr, was increased every 2 hr by 0.13 mmole/kg/hr during a 10-hour period to simulate the arterial NH3 concentrations observed in AHF. Ammonia levels in rabbits administered the NH4-Ac infusion were identical to those observed in AHF, with the exception of the higher initial value in the AHF group. Moreover, the mean rates of increase in grade of encephalopathy in the two groups were similar, although the EEG grades in the infusion group were significantly less at all time points. In conclusion, this study demonstrates that a more pathophysiological approach to identification of the putative toxins in hepatic encephalopathy is feasible. Some of the EEG abnormalities of acute hepatic encephalopathy in rabbits are presumably due to hyperammonemia; the encephalopathy observed in AHF at zero time is probably caused by the previously constructed portocaval shunt via an undefined, but possibly also ammonia-related, mechanism. PMID- 2921863 TI - Measurement of human portal blood flow by continuous thermodilution. AB - We wanted to use the Ganz thermistor catheter, developed to measure blood flow in human coronary sinuses, to measure portal venous flow, which is greater. We prepared a model circuit with a high flow rate and studied the method for suitability and reproducibility of the measurements. Correlation was close between the measured and calculated flow rates when the thermal indicator was injected at the rate of 48 ml/min. Measurements were highly reproducible. The catheter was then tested clinically. It was inserted into the portal trunk during percutaneous transhepatic catheterization to measure the portal venous flow. Measurements in patients with cirrhosis of the liver were close to those reported by other workers, and were reproducible. The results suggest that this method will be useful for the continuous local measurement of portal venous flow that varies with time, and will provide information about portal circulation in hepatic disease. PMID- 2921864 TI - Linear response of collateral cerebral perfusion pressure during carotid clamping. AB - Phenylephrine is frequently used to increase systemic arterial pressure during carotid endarterectomy. However, little is known of its effect on collateral cerebral perfusion pressure, particularly in patients with high collateral cerebral vascular resistance who are at increased risk of cerebral ischemia during carotid clamping. We tested the hypothesis that this subset of patients can have collateral perfusion pressure, and hence collateral cerebral blood flow, increased in a predictable way by elevating systemic arterial pressure. We measured mean systemic arterial pressure (Pa), jugular venous pressure (Pv), and mean carotid back pressure (Pc), and calculated collateral cerebral perfusion pressure (P = Pc - Pv) and the ratio of collateral to ipsilateral hemisphere cerebral vascular resistance (Rc/Rh) in 18 patients with low P. Initial measurements were Pa = 84 +/- 8.8 (mm Hg, mean +/- SD), Pv = 7.8 +/- 3.9, Pc = 26 +/- 5.1, P = 18 +/- 4.5 and Rc/Rh = 3.4 +/- 1.15. During phenylephrine infusion, Pa = 108 +/- 11, Pc = 32 +/- 6.5, and P = 24 +/- 7.2, increases of 29, 23, and 33%, respectively (P less than 0.05). Unchanged were Pv = 8.2 +/- 4.1 (5%) and Rc/Rh = 3.5 +/- 1.30 (3%) (P greater than 0.8). The latter two findings indicate that cerebral perfusion pressure and mean systemic arterial pressure are linearly related according to the fluid mechanics equation governing these parameters: Pa = P(Rc/Rh + 1) + Pv. These results support the use of phenylephrine to increase collateral blood flow during carotid endarterectomy in patients with low cerebral perfusion pressure. PMID- 2921865 TI - In vitro toxicity of topical antimicrobial agents to human fibroblasts. AB - Topical antimicrobial agents are essential to optimal burn care. However, exposure of WI-38 human diploid fibroblasts (ATCC CCL 75) and fresh donor human dermal fibroblasts to silver sulfadiazine and mafenide acetate results in a significant reduction in cell proliferation, as determined by hemocytometer cell counts and total matrix protein assays, within 48 hr of exposure. Changes in cellular morphology and progressive deterioration of cytoplasmic organelles and the nucleus are seen with phase-contrast microscopy and transmission electron microscopy. These findings may explain the clinical observation of delayed wound healing after the use of topical antimicrobial agents. PMID- 2921866 TI - Prevention of bridge binding in immunoassays: a general estradiol tracer structure. AB - Iodinated estradiol tracers were synthesized with three different bridges connecting the radiolabelled moiety to the steroid core: Hemisuccinate, carboxymethyloxime and amide. Taking these iodinated tracers in combination with ten antibodies raised against estradiol-6-CMO-albumin, titers and slopes of calibration curves have been compared to the corresponding data using a 3H tracer. The data indicate that the tracer with the amide bridge is recognized similarly to the tritiated estradiol by all antibodies tested, whereas the two other iodinated tracers exhibit substantial bridge binding. The results suggest that the amide tracer structure can generally be used to improve the quality of estradiol antibodies suffering from bridge binding effects. PMID- 2921867 TI - In vitro evidence for modification of rat liver glucocorticoid receptor binding properties and transformation by hyperthermia. AB - The physico-chemical parameters of the interaction of [3H]triamcinolone acetonide (TA) with the glucocorticoid receptor (GR) and the in vitro activation of glucocorticoid-receptor complexes were studied in liver cytosols of rats exposed to 41 degrees C hyperthermia. A significant reduction in glucocorticoid binding and a slight increase in binding affinity were detected in hyperthermic rats as compared to the controls. The number of binding sites was 0.48 +/- 0.02 and 0.73 +/- 0.03 pmol/mg protein for heat-treated and control rats, respectively. Differences in equilibrium dissociation constants (0.52 +/- 0.08 nM for hyperthermic and 0.94 +/- 0.13 nM for control animals) were reflected in corresponding differences in dissociation rate constants at 25 degrees C (5.1 x 10(-4) and 7.5 x 10(-4) min-1, respectively), whereas association rate constants were similar. The inactivation kinetics of unoccupied GR at 25 degrees C was the same in both groups. Glucocorticoid-receptor complexes in liver cytosol from hyperthermic and control rats were thermally activated to a similar extent, but the activation rate was significantly lower in the former. Mixing experiments with the control and hyperthermic rat liver cytosols suggest that this impairment of glucocorticoid-receptor complexes activation could be at least in part ascribed to heat stress-related changes in the action of activation modulator(s). Sedimentation behaviour of unactivated and activated [3H]TA-receptor complexes of hyperthermic and control rats was identical. PMID- 2921868 TI - Comparative effects of 17 beta-estradiol, progestin R5020, tamoxifen and RU38486 on lactate dehydrogenase activity in MCF-7 human breast cancer cells. AB - The effects of 17 beta-estradiol (estradiol), synthetic progestin R5020 and their antagonists, tamoxifen (Tam) and synthetic RU38486 on lactate dehydrogenase (LDH) activity in MCF-7 human breast cancer cells during the growth period were studied. A specially developed quantitative cytochemical assay was used; LDH activity is expressed per cell, and is thus independent of the positive and negative growth effects of the hormones and antagonists. Estradiol and R5020 stimulated LDH activity after similar exposures (6-48 h) and the stimuli were concentration dependent over the range 10(-7) M to 10(-10) M. As for the antagonists, RU38486 stimulated LDH activity in much the same way as estradiol and R5020; Tam alone, on the other hand, does not stimulate LDH, but when added to estradiol, Tam inhibits estradiol mediated LDH activation. When present at half-stimulant concentration, estradiol + R5020 and estradiol + RU38486 exhibit additive effects on LDH activity. Thus LDH appears to be an interesting tool for the study of hormone and antagonist effects in MCF-7 breast cancer cells. PMID- 2921869 TI - Interaction of antiprogestins with progesterone receptors in rat uterus. AB - Cytosolic and nuclear progesterone receptors (PRc and PRn) under antiprogestin treatment were measured in rat deciduoma and compared with values for contralateral (nondeciduomatous) rat uterine tissue. Uterine PRc and PRn of the progesterone treated group were 101 +/- 8.7 and 4770 +/- 590 fmol/mg DNA respectively. After treatment with antiprogestins STS-557, 5 alpha-DNE, (5 alpha dihydronorethisterone), 5 alpha-DNG (5 alpha-dihydronorgestrel), RU-22092 and RU 16556, PRc in the nondeciduomatous control horn ranged from 127 to 377 fmol/mg DNA and PRn from 2785 to 17925 fmol/mg DNA. In the decidual tissue, PRc decreased significantly (4.6 +/- 0.8 fmol/mg DNA) on 5 alpha-DNG treatment as compared with the progesterone alone treatment group (147 +/- 3.8). PRn in decidual tissue also decreased maximally on 5 alpha-DNG treatment. These results suggest that the interaction of antiprogestins may not be identical in control uterine tissue and in deciduoma. PMID- 2921870 TI - The kinetic mechanism of the hypothalamic progesterone 5 alpha-reductase. AB - The kinetic mechanism of the hypothalamic NADPH-linked progesterone 5 alpha reductase from female rats was determined to be equilibrium ordered sequential by initial velocity, product inhibition and dead-end inhibition studies. Analysis of the initial velocity data resulted in intersecting double reciprocal plots indicating a sequential mechanism (apparent Km (progesterone) = 95.4 +/- 4.5 nM; apparent Kia(NADPH) = 9.9 +/- 0.7 microM). The plot of 1/v vs 1/progesterone intersected on the ordinate which is consistent with an equilibrium ordered mechanism. Ordered addition of the substrates was also supported by product inhibition studies with NADP versus NADPH and NADP versus progesterone. NADP is a competitive inhibitor versus NADPH (apparent Kis = 4.3 +/- 1.3 microM) and a noncompetitive inhibitor versus progesterone (apparent Kis = 31.9 +/- 1.4 microM and apparent Kii = 145.4 +/- 15.5 microM). These inhibition patterns show that NADPH binds prior to progesterone. Taken together, these analyses indicate that the cofactor, NADPH, binds to the enzyme in rapid equilibrium and preferentially precedes the binding of progesterone. PMID- 2921871 TI - No evidence for aromatization of [3H]testosterone in oestrogen receptor containing cells of the epididymis. AB - Oestrogen receptors are found in the principal cells of the caput and in apical and clear cells of the epididymis of the mouse. The distribution pattern of oestrogen receptors is different from that of androgen receptors and suggests a physiological role for oestrogens in the epididymis. We examined by competition experiments and thaw-mount autoradiography to see whether aromatization of [3H]testosterone is the source of oestrogens in the epididymis. After injection of [3H]testosterone we found the same labeling pattern as after non-aromatizable [3H]dihydrotestosterone. In particular, apical and clear cells showed a low or no nuclear concentration of radioactivity as with [3H]dihydrotestosterone. Competition with oestradiol had no effect on the binding pattern of [3H]testosterone in the epididymis in contrast to its effects in the brain of the same animals. Competition with dihydrotestosterone abolished labeling in contrast to the brain, where no effect was observed. Thus no aromatization of [3H]testosterone to oestrogens but conversion to dihydrotestosterone seems to occur in the epididymis. PMID- 2921872 TI - Dissociation of 19-hydroxy- 19-oxo-, and aromatizing-activities in human placental microsomes through the use of suicide substrates to aromatase. AB - Suicide substrates of aromatase were used as chemical probes to determine if free 19-hydroxyandrost-4-ene-3,17-dione (19-OHA) and 19-oxoandrost-4-ene-3,17-dione (19-oxoA) are obligatory intermediates in the aromatization of androst-4-ene-3,17 dione (androstenedione) to oestrone by human placental aromatase. A radiometric HPLC assay was used to monitor 19-hydroxy, 19-oxo-, and aromatized products formed in incubations of [14C]androstenedione and human placental microsomes. When microsomes were preincubated with the suicide substrates 10 beta-mercapto estr-4-ene-3,17-dione (10 beta-SHnorA), or 17 beta-hydroxy-10 beta-mercaptoestr-4 ene-3-one (10 beta-SHnorT), it was found that 19-hydroxy-, 19-oxo- and aromatase activities were inhibited in parallel. However, when the suicide substrates 4 hydroxyandrost-4-ene-3,17-dione (4-OHA) and 19-mercaptoandrost-4-ene-3,17-dione (19-SHA) were preincubated with placental microsomes, significantly greater inhibition of formation of oestrogens was observed in comparison to the inhibition of formation of 19-hydroxy- and 19-oxo-metabolites. Furthermore, significantly more time-dependent inhibition of 19-oxoA formation was observed in comparison to inhibition of 19-OHA formation with these same inhibitors. These results suggest that 19-hydroxy- and 19-oxo-androstenediones are not free, obligatory intermediates in the aromatization of androstenedione by human placental aromatase, but rather are products of their own autonomous cytochrome P 450-dependent, microsomal enzymatic activities. PMID- 2921873 TI - Identification of 20 alpha-hydroxy-5 alpha-pregnan-3-one and 20 beta-hydroxy-5 alpha-pregnan-3-one in human pregnancy urine. AB - 20 beta-Hydroxy-5 alpha-pregnan-3-one and 20 alpha-hydroxy-5 alpha-pregnan-3-one were isolated and identified from a pool of urine collected from women in the third trimester of pregnancy. Following isolation by Sephadex LH-20 and HPLC, the identity of each compound was established by comparison of GC-MS data for the methyloxime-trimethylsilyl ethers with those for authentic standards. PMID- 2921874 TI - Effect of inhibition of prostaglandin synthesis on epinephrine-induced gastroduodenal electromechanical changes in humans. AB - We conducted a double-blind randomized study to investigate the role of endogenous prostaglandins in epinephrine-induced changes in human gastric electromechanical activity. Intravenous administration of a pharmacologic dosage of epinephrine (222 ng/kg per min) caused gastric dysrhythmia in 8 of 12 healthy subjects. After indomethacin treatment, the incidence of epinephrine-induced gastric dysrhythmia was reduced to 4 of 12 healthy subjects, which is similar to the incidence of gastric dysrhythmia noted in the placebo group. The difference, however, was not statistically significant (P = 0.2). Epinephrine also substantially inhibited both the amplitude and the frequency of antral contractions. Indomethacin treatment partially reversed the reduction in the amplitude but not the frequency of antral contractions. These results suggest that endogenous prostaglandins may, in part, regulate the amplitude of human antral contractions; however, the role of prostaglandins in epinephrine-induced gastric dysrhythmia in humans remains uncertain. PMID- 2921875 TI - Acute acalculous cholecystitis. AB - Acute acalculous cholecystitis occurs infrequently, but the incidence seems to be increasing. Its attendant high associated morbidity and mortality dictate prompt diagnosis. Diagnosing this condition is often difficult because of the patient's debilitated medical condition and the limitations of biliary imaging techniques. During a 5-year study period (1981 through 1986), 20 patients underwent assessment and treatment for acute acalculous cholecystitis at our institution. This observation suggests an increase in incidence in comparison with a previously reported review of 28 such patients during a 16-year period at our institution. Initial treatment consisted of cholecystectomy in 18 patients, and percutaneous transhepatic cholecystostomy was successfully used in the other 2 patients. The postoperative mortality and morbidity for these 20 patients were 30% and 55%, respectively. Percutaneous transhepatic cholecystostomy should be explored further as a treatment option for acute acalculous cholecystitis. PMID- 2921876 TI - Proper use of aerosol corticosteroids to control asthma. AB - Aerosol glucocorticoids are highly effective in the treatment of bronchial asthma. Clinically apparent systemic hypercortisolism is virtually nonexistent in patients who receive such therapy, although local effects of candidiasis or dysphonia may occur. Treatment failures can often be attributed to poor patient compliance or incorrect use of the pressurized aerosol inhaler. The addition of a spacer device to the inhaler improves the technique and the results in many patients. Furthermore, many patients with asthma require 2 or 3 times the conventional dose of aerosol corticosteroids for optimal control of pulmonary function. Careful coaching is essential for the successful use of aerosol corticosteroids. PMID- 2921877 TI - Acute acalculous cholecystitis. PMID- 2921878 TI - Ethanol ablation of parathyroid tumors. PMID- 2921879 TI - Thyroxine replacement therapy and bone mineral density. PMID- 2921880 TI - Tuberculosis in the US Hispanic population. PMID- 2921881 TI - Advances in health status assessment. Overview of the conference. AB - Although the art and science of health status measurement have a considerable history that is in some ways as old as the healing arts themselves, interest and developments in this field have accelerated in the last two decades. To take advantage of this encouraging environment, the Henry J. Kaiser Family Foundation sponsored its second conference on Advances in Health Status Assessment. It had two major goals: first, to let developers and potential users of health assessment tools explore further the conceptual and methodologic issues of particular concern to them; second, to highlight advances in applying these tools to clinical practice, clinical and biomedical research, and policy research. This monograph reports on the proceedings of that conference: three overviews and nine empirical reports in the above mentioned areas, one special report on health promotion, and four studies on particular methodologic issues: barriers to the use of health status assessment instruments; the advantages and limitations of generic and disease-specific measures; incorporating patient utilities into health status measures; and discounting. The conference highlighted both the considerable advances made in this field in the recent past and the numerous conceptual, methodologic, and practical problems yet to be resolved. PMID- 2921882 TI - Advances in health status assessment: conference proceedings. July 13-15, 1988, Menlo Park, California. PMID- 2921883 TI - Patterns of change in disability and well-being. AB - Longitudinal data that track the course of disability and well-being are being collected for older populations, with remeasurements taken at annual or longer intervals. These can miss much of the genuine dynamics that older people experience. This analysis uses a data set with fine-grained data on health and function. It involves 165 persons ages 55 and over who were followed for minimum of 1 year (up to 2 years) after hospitalization for a chronic condition (six of which were specified). Within that period, each person had nine separate contacts for assessment of cognitive, physical, social, and emotional function. Respondents also kept health diaries continuously for a year. This article reports patterns of change for the diaries only, focusing on two items recorded daily: self-rated health and activity level. We analyze the data visually, by plots of these items over time for each person, and statistically, by numerical indicators of changes and levels for the items. Differentials in changes and levels by patient characteristics (e.g., age, sex, marital status, diagnosis) were explored. Most people experience a posthospital improvement, with the majority attaining their usual levels of well-being and activity, despite their serious illness. But this recovery is usually interrupted by episodes of low well being and activity and even further hospital stays. Statistical analyses show that, overall, physical health suffers a small decline over the year whereas activity levels tend to improve. Health is worst and activity levels lowest, gains are smallest and declines largest, for elderly (ages 75 and older) men and for nonmarried people, especially men. Together, the visual and statistical analyses confirm the profound dynamics in health and function that middle-aged and older people with chronic conditions experience. PMID- 2921884 TI - Multidimensionality of health status in an elderly population. Construct validity of a measurement battery. AB - Although health is generally accepted to be a multidimensional construct, the relationship among various domains has not been well defined. To understand this issue better we used principal components analysis to examine the relations among a set of health status measures gathered on 590 elderly members of a health maintenance organization (HMO). These included functional health, emotional health, social activity within and outside of the family, and cognitive functioning (all based on patient interview), physicians' ratings of patients' health, and chart-derived data on physiologic health. Support was obtained for the umbrella concept of "health" as well as for six subcomponents: functional health, emotional health, physiologic health, both kinds of social activity, and cognitive functioning. Patients' ratings of their overall physical and mental health were related to functional, physiologic, and emotional health factors, whereas physicians' ratings of overall physical and mental health were never related to the emotional health factor. This suggests that patients may hold a broader frame of reference in gauging overall health than physicians do. PMID- 2921885 TI - The Quality of Well-being Scale. Applications in AIDS, cystic fibrosis, and arthritis. AB - The Quality of Well-being (QWB) Scale combines preference-weighted measures of symptoms and functioning to provide a numerical point in-time expression of well being that ranges from zero (0) for death to 1.0 for asymptomatic optimum functioning. The QWB includes three scales of function: mobility, physical activity, and social activity. Each step of these scales is associated with preference weights. Preference adjustments for symptoms are also included. This paper describes how this general system was used to evaluate outcomes in three different clinical conditions: acquired immune deficiency syndrome (AIDS), cystic fibrosis, and arthritis. In one study, the QWB was administered to 31 patients participating in evaluation of azidothymidine (AZT) treatment for AIDS. The QWB system demonstrated substantial benefits of AZT treatment in comparison to placebo. In a second study, the QWB and a series of pulmonary function measures were administered to 44 patients with cystic fibrosis. The QWB was demonstrated to be significantly correlated with measures of pulmonary function, including FEV1 and maximal midexpiratory flow rate (MMEFR). In addition, there were significant associations between the QWB and measures of exercise tolerance. In the third study, the QWB and an arthritis-specific measure were administered to 83 arthritis patients before and after their treatment. The QWB was at least as capable of detecting clinical change in this population as was the disease specific measure. For all three conditions, the QWB considered side effects and benefits of treatment in a common unit. Clinical trial data are cited to suggest that the QWB is a valuable outcome measure in arthritis treatment evaluation. We conclude that the QWB has substantial validity as a general health outcome measure and that the system can be used with different populations. PMID- 2921886 TI - General versus disease-specific measures. Further work on the Sickness Impact Profile for head injury. AB - Three modifications devised to make the Sickness Impact Profile more sensitive to head injury are evaluated in 202 head-injured and 132 general trauma patients 1 month and 12 months after injury. The modifications consist of adding items, deleting nonapplicable items, and reweighting areas of function. Each of the modifications, and especially all three combined, slightly but significantly improve discrimination of head-injured and comparison subjects and increase correlations with neurologic and neuropsychologic severity indexes. These slight improvements occur more often at 12 months than at 1 month and among those without rather than with pre-existing conditions. No improvements are found in the ability to classify patients into subgroups. The modifications fail to make improvements sufficiently large or consistent to provide a practical advantage over the SIP. The standard SIP provides a reasonable measure of psychosocial functioning following head injury. It relates to head injury and other system injury severity and reflects recovery with time. The SIP score relates to emotional functioning even after injury severity has been taken into account. Until other factors, such as emotional status and responses style, are better controlled, little benefit is likely to be obtained from creating disease specific psychosocial measures. PMID- 2921887 TI - Assessment of children's health status. Field test of new approaches. AB - The assessment of children's health status presents unique difficulties. These include parent-child differences in reports of functioning, knowledge of what constitutes age-appropriate functioning, obtainment of accurate information for child, and demonstration of the predictivity of health status measures. Recent measures (the Functional Status II-R and instruments from the RAND Health Insurance Experiment) address physical, social, and psychologic domains of children's health. The authors modified these instruments to develop short (7 and 14 items) questionnaires (RAND, FSQ) to assess child health. Scoring on these questionnaires was compared with traditional measures of illness severity and medical service utilization. The authors also evaluated coding illness-specific and general health limitations (FSQ-S and FSQ-G, respectively). Patients included the parents of 113 children with chronic illness (100 asthmatics). Measure stability was evaluated over a 6-month period in a subset of patients. Internal consistency (Cronbach's alpha) of the seven-item RAND measure was .78, the FSQ-S .78, and the FSQ-G .73 to .89 during repeated samplings over 6 months. The FSQ-S and Rand seven-item measure were moderately correlated (.47, P less than .001). The authors observed significant correlations among alternate codings of the FSQ and RAND and between the FSQ-S, FSQ-G, RAND, and severity measure with traditional indices of medical service utilization. Parents were more likely to attribute certain functional status problems (e.g., being tired) to illness than they were other problems (e.g., moodiness or interest in things). The findings demonstrate that these measures have acceptable psychometric properties and provide preliminary evidence of construct validity in a group of young children with asthma. Using general and specific measures will provide differing pictures of a child's functioning. No single measure completely taps the impact of illness as measured by a panel of traditional indicators of illness burden and medical service utilization. PMID- 2921888 TI - Using composite health status measures to assess the nation's health. AB - Research in progress at the National Center for Health Statistics for evaluating the usefulness of composite measures of health status for assessing the nation's health is described. Three measures suitable for use in the general population, the Health Insurance Experiment-Functional Limitations (HIE-FL), the Health Utility Index (HUI), and the Quality of Well-being (QWB) scale, have been mapped to data collected in the 1980 National Health Interview Survey (NHIS). Analysis using current algorithms for making composite function status measures according to the QWB methods suggests that traditional single indicators of health tend to overestimate the level of health by about 10%. When symptoms and problems are added to the composite function score, the overestimate as measured by the single indicator is at least 50%. The authors are continuing to validate these algorithms, to develop similar ones for the HIE-FL and HUI, and to extend the analysis to data collected in 1977, 1979, and 1984. Current results indicate that to realize fully the benefits of composite measures, well-established, valid, and reliable measures of health-related quality of life should be included as part of the regular NHIS data collection procedures. PMID- 2921889 TI - Using proxies to evaluate quality of life. Can they provide valid information about patients' health status and satisfaction with medical care? AB - Instruments using interview data to measure health status have been increasingly used to measure patient outcomes. To assess the potential utility of proxy responses about health status when subjects are unable to respond, the authors compared the responses of 60 subject and proxy pairs on instruments measuring overall current health, functional status, social activity, emotional health, and satisfaction with medical care. Proxies were asked to respond as they thought the subject would. Subject and proxy responses were strongly correlated with each other for overall health, functional status, social activity, and emotional health (P less than .001), and moderately correlated for satisfaction (P less than .005). Proxies reported lower emotional health and satisfaction than did subjects (P less than .005). Proxy and subject mean responses were generally similar for overall health, functional status, and social activity. However, those proxies who spent more time per week helping the subject rated the subject's functional status and social activity as more impaired than did the subject (P less than .05). Subjects who had poorer overall health tended to rate their health relatively lower than did the proxies (P less than .05). These results suggest that use of proxies intermingled with subjects to measure health status through interview may lead to biased results. PMID- 2921890 TI - Health perceptions of primary care patients and the influence on health care utilization. AB - This prospective study was conducted to determine the influence of primary care patients' health perceptions on their utilization of health care services. Patients' health perceptions were measured using the RAND Corporation's General Health Perceptions Questionnaire. Physicians provided scores of how they thought the patients perceived their health and of actual physical and emotional health. Utilization data (number of office visits, number of telephone calls to the physician, and ambulatory charges) were evaluated for a 12-month period after completion of the questionnaire. Of 208 patients, 62 (30%) patients with health perceptions scores less than 50 had greater degrees of anxiety (P less than .001), depression (P less than .001), health-related worry (P less than .001), and felt less able to resist illness (P less than .001) than patients with higher health perception scores. Analysis of covariance was used to control for differences in physical health among groups of patients with varying health perceptions. These analyses revealed that patients with low health perceptions made more office visits (P = .002), more telephone calls to the physician (P = .01), and had more office charges (P = .05) than patients with higher scores. Physicians accurately predicted the patients' health perceptions in 49% of the cases. In 37%, they thought patients would score their health perceptions higher than they did; in 14% they thought patients would score their health perceptions lower. Health perceptions are an important factor contributing to the use of health care by primary care patients, regardless of the patient's actual physical health. Persons with low health perceptions account for approximately 5% of office visits, a clinically important fraction, especially when compared to the 9% of office visits for hypertension, the most common disease treated in the medical office. PMID- 2921891 TI - [Quo vadis, psychiatry?]. PMID- 2921892 TI - [Interleukins--hormones of immunologic defense]. PMID- 2921893 TI - [Risk of overestimation of non-pharmacologic treatment of hypertension?]. PMID- 2921894 TI - [PO2 value is less reliable when frozen blood specimens are used]. PMID- 2921895 TI - [Ultraviolet rays are not cytotoxic]. PMID- 2921896 TI - [Combined drug therapy against Campylobacter in duodenal ulcer and non-ulcerous dyspepsia]. PMID- 2921898 TI - [Large dose of medicine in the National Encyclopedia. Also, wrong terms by the national linguistic standards]. PMID- 2921897 TI - [Anal incontinence--examination and treatment]. PMID- 2921899 TI - [Vaccines today and tomorrow]. PMID- 2921901 TI - [Social medicine. The usefulness of research in social medicine--from practical application to ideas]. PMID- 2921900 TI - [Terminal care programs]. PMID- 2921902 TI - [123 cases of adverse effects of alternative medicine. Several severe injuries after a stay at a health resort]. PMID- 2921903 TI - [Bengt Winblad, geriatric researcher: the need for care increases with more and more people over the age of 80]. PMID- 2921904 TI - [A valuable publication about the role of general medicine in the future]. PMID- 2921905 TI - [Fetal surgery--surgical incompetence or a realistic treatment alternative?]. PMID- 2921906 TI - [Risk of overvaccination against tetanus--who is deciding: the National Board of Health and Welfare or the manufacturer?]. PMID- 2921907 TI - [Award-winning poster on wound management]. PMID- 2921908 TI - [Fibromyalgia--an entity?]. PMID- 2921909 TI - [Platelet activating factor--a new agent to control asthma]. PMID- 2921910 TI - [Family therapy often has a good effect on psychiatric problems]. PMID- 2921911 TI - [Tinnitus--examination, management and treatment]. PMID- 2921912 TI - [An effective peroral cholera vaccine developed in Sweden]. PMID- 2921913 TI - [A promising new vaccine against typhoid fever]. PMID- 2921914 TI - [A dramatic spread of HIV in Southeast Asia. The number of infected addicts using syringes increased from 16 to 43 per cent in 1 year in Thailand]. PMID- 2921915 TI - [The status of the human embryo in ideologic history--an erroneous translation of the Holy Bible influences the debate on abortion]. PMID- 2921916 TI - [Ethics in life's borderland. Keep human life and biological life apart and experience and medically prove death]. PMID- 2921918 TI - [Time for Swedish education in the science of public health]. PMID- 2921917 TI - [How ought the science of public health be developed?]. PMID- 2921919 TI - [It is unreasonable to demand a time limit in government-supported education in psychotherapy]. PMID- 2921920 TI - [Delegation of aged challenges primary care as the basis of geriatric hospital care]. PMID- 2921921 TI - [To drink moderately--good and bad for the cardiovascular system]. PMID- 2921922 TI - [Does the number of menstrual cycles influence the risk of breast cancer?]. PMID- 2921924 TI - [Treatment of dermatoses using the Bucky method is effective and comfortable for the patient]. PMID- 2921923 TI - [Analyses of serum potassium in outpatients can be done at comparatively long intervals]. PMID- 2921925 TI - [Iontophoresis in hyperhidrosis depresses sweating]. PMID- 2921926 TI - [Hazardous work and predictors of hand eczema--vocational guidance of patients with atopic allergy]. PMID- 2921927 TI - [Bipolar esophageal ECG improves diagnostic possibilities]. PMID- 2921928 TI - [How acute is psychiatric consultation?]. PMID- 2921929 TI - [Abdominal aortic aneurysm with aortocaval fistula--a rare complication]. PMID- 2921930 TI - [Aneurysm of the aortic arch treated surgically under hypothermia and circulatory arrest]. PMID- 2921931 TI - [Perimyocarditis with elevated cardiac enzymes caused by Borrelia infection]. PMID- 2921932 TI - [Prevention with agents affecting uterine contraction is seldom necessary in the third stage of labor]. PMID- 2921933 TI - [Social medicine]. PMID- 2921934 TI - [Collagen antibodies and their effect on wound healing]. AB - The influence of antibodies to collagen on wound healing was tested by the use of a standard incision wound in rats. The antisera--specific for the terminal determinants of the collagen molecule--were obtained from rabbits immunized with rat--or pig--skin collagen and injected intraperitoneally, i.e. systemically. Generalized immune reactions or signs of incompatibility were not observed. The injection of antisera on the 7th postoperative day led to a significant gain of tensile strength. This effect was achieved by the homologous antiserum (p less than 0.01) as well as by the heterologous antiserum (p less than 0.04). The heterologous antiserum further induced a significant fall of free serum hydroxyproline (p less than 0.005). The application of the heterologous antiserum on the 14th postoperative day caused a significant decrease of tensile strength (p less than 0.006). The results are referred to collagen-specific immune reactions and varying conditions in the wounded area during different phases of wound healing. PMID- 2921935 TI - [Chronic osteomyelitis and cancer of the fistula]. AB - Malignant change following chronic osteomyelitis with draining sinuses is rare (0.38-2.7%). The time from onset of osteomyelitis until malignant changes differs but needs 30 years in an average. Most patients are men between 50 and 60 years of age. If there is any doubt about malignancy (bleeding, tumor growth) biopsy should be performed and repeated if histological findings give no clear diagnosis. Metastases should be excluded by x-ray of the chest, scintigram and CT of the regional lymphnodes. Correct surgical therapy can only be done by amputation or exarticulation of the extremity. Patients who were operated upon malignant carcinoma of a sinus after osteomyelitis ought to be controlled in a regular follow-up including blood test (tumor marker). PMID- 2921936 TI - [AIDS--current significance in surgery]. PMID- 2921937 TI - Tryglycylvasopressin-reduced portal and systemic concentrations of serum bile acids after exogenous chenodeoxycholic acid load in rats as a reflection of reduced splanchnic blood flow. AB - The effect of triglycylvasopressin (TGVP) on the absorption of chenodeoxycholic acid (CDCA) was investigated in three groups of six rats (controls, CDCA, CDCA + TGVP) through the evaluation of portal and caval serum bile acids (SBA) concentrations after an oral load with CDCA to investigate whether changes in this parameter reflect variations in splanchnic blood flow induced by a vasoconstrictor. The results indicate that CDCA was absorbed and led to a significant increase in SBA. This increase was reduced by TGVP administration: portal blood 380.0 +/- 61.2 vs 279.7 +/- 45.3; caval blood 151.8 +/- 45.7 vs 41.7 +/- 12.5 (mumol/l; mean +/- s.d.). This suggests that variations in SBA concentrations could reflect changes in splanchnic circulation. PMID- 2921938 TI - Caroli's disease and adult polycystic kidney disease: a rarely recognized association. AB - Caroli's disease is a rare form of fibropolycystic disease of the hepatobiliary system characterized by segmental cystic dilatation of intrahepatic ducts. It is associated with intrahepatic cholelithiasis, cholangitis and hepatic abscesses. Like other forms of fibropolycystic disease of the liver, Caroli's disease is often accompanied by cystic renal disease, specifically renal tubular ectasia or medullary sponge kidney. Adult-type polycystic kidney disease associated with Caroli's disease is rare, only one such case having appeared in the literature to our knowledge. We present a second instance of this association. PMID- 2921939 TI - Relation of sinusoidal stenoses following hepatocyte swelling to hepatic vascular resistance in experimental liver cirrhosis. AB - To investigate the significance of sinusoidal stenoses and a decrease in the sinusoidal bed due to hepatic cell swelling as a factor increasing hepatic vascular resistance in liver cirrhosis, hepatic vascular resistance in choline deficient diet-induced cirrhotic rats was measured by an isolated liver perfusion method. In the cirrhotic rats, the swollen hepatic cells resulting from accumulation of fat droplets narrowed the sinusoids and decreased the sinusoidal bed. Consequently, the hepatic vascular resistance was increased by 2.7 times normal (8.60 +/- 2.32 mm H2O.ml-1.min; controls, 3.13 +/- 0.67 mm H2O.ml-1.min), and portal hypertension was also recognized (188.1 +/- 26.3 mm H2O; controls, 114.2 +/- 12.8 mm H2O). In the cirrhotic rats fed with ordinary rat pellets for 2 months, however, the sinusoidal stenoses and the decreased sinusoidal bed recovered to nearly normal as a result of disappearance of the fat droplets in the hepatic cells. The increased hepatic vascular resistance was decreased to 1.5 times normal (4.68 +/- 0.82 mm H2O.ml-1.min), and the elevated portal vein pressure was reduced (141.5 +/- 17.4 mm H2O). These findings clearly demonstrate that an important factor leading to an increase in hepatic vascular resistance is sinusoidal stenoses and a decrease in the sinusoidal bed resulting from swollen hepatic cells. PMID- 2921940 TI - Protective effect of prostaglandin E1 (PGE1) on energy metabolism and reticuloendothelial function in the ischemically damaged canine liver. AB - The protective effects of PGE1 on ischemia-related liver damage were evaluated in dogs. Ninety minutes warm hepatic ischemia was induced by the total clamping of hepatic inflow vasculatures with portal bypassing. The survival rate improved up to 62.5% when PGE1 was administered intravenously prior to ischemia, while no dog survived for longer than 1 week in the nontreated group. Hepatic ATP content was restored up to 80% of preischemic level 2 h after reflow in the PGE1 pretreated group, compared to 55% recovery in the nontreated group. Complete normalization of hepatic energy charge and rapid decrease of lactate were also seen in the PGE1 group. The clearance rate of intravascular lipid emulsion remained fairly normal in the PGE1 group, thereby suggesting well-preserved hepatic reticuloendothelial functions. The serum activities of beta-glucuronidase, GOT and GPT were suppressed in the PGE1-pretreated group, thereby implying a well-protected hepatic integrity. The histology revealed well-preserved hepatic architecture. The remarkable cytoprotective effect of PGE1 on hepatic ischemia shown in this study indicates that PGE1 warrants further study for protection of ischemically compromised hepatic allografts. PMID- 2921941 TI - Rheumatoid aortitis: a rarely recognized but clinically significant entity. AB - Aortitis as a feature of rheumatoid arthritis is considered rare. We have, however, identified 10 patients with aortitis from among 188 consecutive autopsy cases of rheumatoid arthritis. There were 5 men and 5 women with a mean duration of rheumatoid arthritis of 9.6 years. Nine were rheumatoid factor positive and had associated nodules. In addition to standard treatment regimens, 9 patients received corticosteroids. Although involvement of the thoracic aorta was most common, involvement of both the thoracic and abdominal aorta was present in 4 cases. Two patients had aneurysmal dilatation of the thoracic aorta and 1 of the abdominal aorta. Microscopic features of aortitis included necrosis of medial smooth muscle and elastica, with an inflammatory infiltrate comprising primarily lymphocytes and plasma cells. A panmural aortitis was seen in 3 cases. Rheumatoid granulomas were noted in the aortic wall in 5. The diagnosis of aortitis was not made until autopsy in any case. Aortitis was hemodynamically significant in 3 patients. Two had congestive heart failure secondary to thoracic aortitis and aortic valvulitis, and 1 had rupture of an abdominal aortic aneurysm at a site involved by aortitis. Seven patients had rheumatoid vasculitis with a mean of 10 organs involved. Six of these died of complications directly related to vasculitis, including 4 patients with coronary arteritis and associated myocardial infarction. Aortitis can be a feature of severe rheumatoid arthritis and is often associated with rheumatoid vasculitis. Hemodynamic compromise does occur and may be fatal. PMID- 2921942 TI - Inferring the number of evolutionary events from DNA coding sequence differences. AB - The estimation of the amount of evolutionary divergence that has taken place between two DNA coding sequences depends strongly on the degree of constraint on amino acid replacements. If amino acid replacements are relatively unconstrained, the individual nucleotide is the appropriate unit of analysis and the method of Tajima and Nei can be used. If amino acid replacements are constrained, however, this method is shown to be inapplicable. For sequences with strong amino acid constraints, a method is outlined analogous to the Tajima and Nei method using codons as the unit of analysis. Only synonymous substitutions are used. Codon usage data can be employed to estimate the necessary parameters of the calculation, or a priori models of substitution may be employed. Sequences with significant but intermediate constraints on amino acid replacements are, in principle, unanalyzable. PMID- 2921943 TI - Evolution of homologous domains of cytoplasmic intermediate filament proteins and lamins. AB - The earliest gene duplications in the evolution of the intermediate filament proteins created the ancestors of acidic keratins, basic keratins, nonepithelial intermediate filament proteins, and lamins. Biochemistry and function of cytoplasmic intermediate filaments differ greatly from those of lamins. Cytoplasmic intermediate filament proteins have a different cellular location than lamins, form different types of supramolecular structures, and are missing a protein segment found in lamins; but the data presented here indicate that the cytoplasmic intermediate filaments do not have a common ancestor separate from the ancestor of lamins. In the non-epithelial intermediate filament branch, the ancestor of neurofilament proteins and the common ancestor of desmin, vimentin, and glial fibrillary acidic protein (GFAP) diverged first. By evolutionary criteria, the intermediate filament protein recently discovered in neuronal cells does not belong to the neurofilament family but is more closely related to desmin, vimentin, and GFAP. Sequences of different sub-domains yield different evolutionary trees, possibly indicating existence of sub-domain-specific functions. PMID- 2921944 TI - Rapid evolution of variants in a rodent multigene family encoding salivary proteins. AB - A survey of polypeptides encoded by RNA isolated from the submandibular glands of members of the Muridae (species of Mus and Rattus), in conjunction with cDNA cloning, has identified a class of salivary proteins that we term "spot proteins." Although clearly homologous, these proteins show dramatic differences between species in their polypeptide length. On the basis of the sequence of the corresponding clones, it is inferred that the rat spot 1 protein has a size of 6,370 daltons (Da), whereas that of the inbred mouse spot 1 is 11,603 Da. A second component is expressed in some stocks and strains of Mus, and this spot 2 protein has a size of up to 19,212 Da. The sizes of the corresponding mRNAs show parallel differences, and the variation in the sizes of mRNAs in different species of Mus correlates with the pattern of speciation, the size increasing with increased relatedness to inbred mice. The spot protein sequence comprises three domains: an N-terminal domain rich in hydroxy and acidic amino acids, a central domain consisting of repeats of a 9-amino-acid sequence, and a C-terminal domain that in the mouse is very basic. Variation in the number of repeats largely accounts for the differences in size between the mouse and rat mRNAs and their encoded polypeptides, and the coding sequence appears to have been expanding during speciation in the Muridae. There is extensive divergence in sequence between the mouse and rat mRNAs and their encoded proteins. The pattern of amino acid replacements and nucleotide substitutions is consistent with little, if any, selection constraint on the precise sequence of the spot proteins, suggesting that it is the overall architecture of the molecule, rather than the precise structure, that is important for function. There is strong evidence for a gene conversion event having occurred between the two mouse sequences. Frequent recombination by unequal crossing-over between spot protein coding sequences, if it occurs between active and silent genes, could account not only for the expansion in their size but also for their rapid divergence. PMID- 2921945 TI - A horizontal intravital microscope-plus-bone chamber system for observing bone microcirculation. AB - A horizontal intravital microscope has been built which utilizes the telescope optics format with infinity-corrected objectives. The intravital stage accomodates a rabbit into which a tibial bone chamber has been implanted. The chamber is itself an optical component and is considered an integral part of the system. Each animal is observed in supine position with its implanted leg held in an adjustable spring-loaded yoke which aligns the bone chamber in the optical axis. Long working-distance objectives and condensers allow for viewing of the slit-gap tissue in the bone chamber with both transmitted and epi-illumination; the latter being applied for fluorescence studies. A unique feature of the system is a transfer lens holder which can be relocated within the microscope tube. This adjustable lens holder allows for changing of transfer lenses, thereby freeing the investigator to utilize objective lenses with preferred numerical apertures for a given image size. PMID- 2921946 TI - The path of retrograde flow from the lumen of the lateral saphenous vein of the dog to its vasa vasorum. PMID- 2921947 TI - Relationship between phasic changes in human skin blood flow and autonomic tone. AB - Heart rate beat-to-beat oscillations synchronous with respiration and blood pressure waves, have been found to be a marker of sympathovagal interaction in man and animals. Oscillations of heart rate, respiration, and cutaneous blood flow were simultaneously recorded to assess the relationship between autonomic nervous control and cutaneous circulation in a group of 21 healthy subjects and in a group of 6 healthy patients after brachial plexus anesthesia and consequent sympathetic blockade. In the first group, changes in posture were employed to modify autonomic tone. Relative changes in cutaneous blood flow were recorded by laser-Doppler flowmetry. Spectral analysis techniques (cross-correlation) were used to quantify the relationship between oscillations common to the recorded signals. A standing maneuver induced a significant decrease of the cross correlation between respiratory and heart rate fluctuations (from 4.93 +/- 0.16 to 4.44 +/- 0.16 a.u.; P less than 0.001), and a significant increase of the cross-correlation between heart rate and skin blood flow fluctuations (from 0.64 +/- 0.31 to 1.33 +/- 0.21 a.u.; P less than 0.001), but did not modify the cross correlation between respiratory and skin blood flow fluctuations (from 2.87 +/- 0.15 to 3.04 +/- 0.14 a.u.; NS). After the standing maneuver the maximum correlation between heart rate and skin blood flow was always due to oscillations in the range of 0.1 Hz (or 10-sec period), similar to the oscillations described in large arteries. Sympathetic blockade reduced significantly the cross correlation between heart rate and skin blood flow (P less than 0.001). These results suggest that the cross-correlation between skin blood flow and heart rate at 10-sec period fluctuations can be used as an index of the influence of the autonomic tone on skin blood circulation. PMID- 2921948 TI - Arteriolar vasoconstriction and tachyphylaxis with intraarterial angiotensin II. AB - Several aspects of the differences between the responses of the second- to fifth order arterioles (A2 to A5) to intraarterial administration of angiotensin II (AII) were studied by intravital microscopy on an original preparation of rat cremaster muscle. Dose-response curves displayed a leftward shift when the arteriolar order increased. Doses inducing 50% vasoconstriction were 15.1, 0.51, and 0.08 micrograms for A3, A4, and A5, respectively. For A2, very small vasoconstriction was found even at the highest dose of angiotensin II. The dynamics of the response were also dependent on the arteriolar order. The duration of the peak of vasoconstriction increased from A3 to A5, and the interval between the contact of vascular wall with drug and the response was smaller in A4 and A5 than in A3. To understand the effect of diameter as a determinant of heterogeneity in the degree of arteriolar vasoconstriction, norepinephrine was administered under the same conditions as angiotensin II, and responses were measured on arterioles with the same morphological characteristics as those examined after angiotensin II. When comparing the regression curves for the percentage of vasoconstriction vs diameter, we found that this relationship was drug dependent. The significantly steeper slope for angiotensin II than for norepinephrine excluded the possibility that heterogeneity of the degree of vasoconstriction is solely due to differences between the morphological characteristics of the arterioles. Since tachyphylaxis to AII is considered to be a reflection of the drug-receptor interaction, we also studied the magnitude of this phenomenon from proximal to distal parts of the arteriolar network. We showed that the degree of partial tachyphylaxis after 1 microgram AII was dependent on the arteriolar order and a decreasing tachyphylaxis gradient was evidenced from A3 to A5 arterioles. PMID- 2921949 TI - Modification of anionic sites in myocardial capillary basal laminae of diabetic rats. AB - Capillary basal laminar thickening is a distinctive feature of diabetic microangiopathy; however, the mechanism responsible for this abnormality remains to be clarified. Recent reports have described a reduction in the distribution of anionic sites in diabetic glomerular basement membranes, with the suggestion that this reduction may generate a compensatory synthesis of basal laminar constituents, causing laminar thickening. In order to provide additional information, the character and distribution of the basal laminar anionic profile were examined in the myocardium of diabetic rats. Diabetes mellitus was induced in 14 rats by injection with streptozotocin, ip; 6 rats served as controls. Myocardial tissue was subjected to Charonis' procedure for the demonstration of anionic sites with the cationic electron-dense dye, ruthenium red, following the sacrifice of the animals at intervals up to 11 months after the induction of the diabetes. The tissues were then processed routinely for electron microscopic examination. A total of 20 electron micrographs, at magnifications of 13,000x and 33,000x, were obtained from each rat for the quantitation of anionic sites. A length measuring 6 micron along each basal lamina was utilized for determining the number of anionic loci. Results of this study show that (1) the number and size of anionic sites in myocardial basal laminae is reduced in diabetic rats, (2) this decrease becomes more pronounced with prolongation of the diabetes, (3) it is detectable prior to the demonstration of basal laminar thickening by electron microscopy, and (4) enzyme digestion treatments indicated that heparan sulfate proteoglycan is the essential stainable component of the anionic sites. These findings provide evidence that the laminar anionic profile is altered in the diabetic myocardium and support the view that this abnormality constitutes a significant initial event in the pathogenesis of basal laminar thickening. PMID- 2921951 TI - How does AIDS affect the Chinese? PMID- 2921950 TI - The effect of anesthetics on lymphatic contractility. AB - Spontaneous contractions and those elicited by electrical stimulation were studied in isolated segments of bovine mesenteric lymphatic vessels. The effects of three general anesthetics, pentobarbitone, halothane, and ether, on these spontaneous and evoked contractions were studied. Pentobarbitone and halothane inhibited spontaneous contractions in a dose-dependent fashion. In doses of 10( 4) M or greater both drugs completely abolished spontaneous contractility but when contractions were elicited by electrical stimulation pentobarbitone inhibited them in a dose-dependent manner whereas halothane did not. In contrast to the above results ether in doses as high as 10(-2) M had little effect on lymphatic contractility. It is concluded that, in doses similar to plasma levels found during general anaesthesia, halothane and pentobarbitone significantly depressed lymphatic contractility while ether did not. PMID- 2921952 TI - Asian culture and communications in midwifery. PMID- 2921953 TI - School nurses and professional status. PMID- 2921954 TI - Psychological effects of lower section caesarean. PMID- 2921956 TI - "The politics of health". PMID- 2921955 TI - What parents should know about asthma. PMID- 2921957 TI - MIDIRS: a database for midwives. PMID- 2921958 TI - Education reform and speech therapy. PMID- 2921959 TI - Special delivery? PMID- 2921960 TI - Gamete intrafallopian transfer (GIFT)--a treatment for infertility. PMID- 2921961 TI - Sexuality--before and after birth. PMID- 2921962 TI - Carers' careers--contingencies and crises. AB - A review of the literature on employment decisions shows that chance events vary in their contribution to the employment decision. The nature of these events varies between being quite favourable to being almost totally malign. The uncertainties involved in student midwives' employment decisions require certain strategies to be used to make allowance for these chance events, which may assume the proportions of crises. The recent study of student midwives' employment decisions demonstrates the nature of some of the uncertainties with which they are faced and the ways in which they cope. Conclusions are drawn concerning the significance of these processes for midwife managers. PMID- 2921963 TI - The holistic health care of couples undergoing IVF/ET. AB - The purpose of this paper is to discuss the role of health professionals as educators, counsellors and support system persons for couples undergoing in-vitro fertilisation/embryo transfer (IVF/ET). All health care professionals must take a more assertive role in promoting the holistic health care approach to IVF patients so that they may be protected from unnecessary emotional distress. Prolonged insensitive evaluations with no clear end in view intensify frustrations and erode the patient's self-esteem. Comprehensive medical/nursing services are needed, as well as ongoing education, counselling and psychological support. Holistic health care considers all diagnostic and therapeutic modalities. Emphasis should be put on answering patients' questions, allaying fears and recognising any medical or psychological factors that may be important during the course of therapy. Adequate pre- and post-operative preparation of the couple should be a priority for health professionals. PMID- 2921964 TI - [The point of attack on DNA]. PMID- 2921965 TI - [Risk of HIV infection at the research laboratory]. PMID- 2921966 TI - A light source for testing radiological television cameras. AB - A light source for testing and setting up radiological television systems has been designed and built using green light emitting diodes and an optical integrating sphere. It is shown to have an optical spectrum similar to the green output phosphors used in x-ray image intensifiers (XRII's). It can be made uniform in intensity across the output port and does not show the small scale granularity characteristic of phosphors. It has a Lambertian angular distribution which, by the addition of neutral density filters, can be made to mimic the angular distribution at the output of an XRII. It can easily and accurately be modulated or switched and a luminance comparable to that of an XRII output phosphor can be achieved. PMID- 2921967 TI - A new photoconductor imaging system for digital radiography. AB - Amorphous selenium is a material often used in the x-ray imaging system. The main application is in xeroradiography where the structure of the sensor is a layer of selenium on a conductive substrate. The signal is a charge density on the surface which is revealed by a toner or by electrostatic probe for digitalization. In the system described here, the sensor structure is different for the sensor is covered by an electrode, a thin layer of metal, which gives another interface. The reading system needs the scanning of a light beam and the resolution power depends on the size of the beam. It is easier to scan a light beam than electrostatic probes so a more compact system can be realized. In the process, there are two phases: the storage and the reading. The time spent between the two phases reduces the quality of the image, and an in situ reading system, integrated to the radiographic machine will be, for this reason, more efficient. Also, the sensor needs good memory effect. One has investigated different sensors based on a structure of a thin photoconductive layer between two electrodes to find a memory effect. We have already seen this phenomena in the Bi12 SiO20 (B. Richard, "Contribution a l'etude d'un procede d'imagerie radiologique utilisant le photoconducteur BO12 SiO20," Ph.D. thesis, Paris, 1987). In amorphous selenium with some dopants and some type of metallic contact, the memory effect is important enough to realize a system. With 2 X 2 cm samples, a complete x-ray digital imaging system has been built.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2921968 TI - Linearity and contrast scale control in computed tomography. AB - The aim of this paper is to present linearity studies and quality control charts for changes in the computed tomography (CT) number of water and contrast scales for two CT scanners over one year. Linear regression relates the attenuation coefficient to CT number. The CT number for water and the contrast scale values as obtained from the fit are: CT1 = (-0.13 +/- 1.3) Hounsfield units (HU), CT2 = (-1.8 +/- 1.6) HU and contrast scale (CS)1 = (1.80 +/- 0.03) 10(-4) cm-1 HU-1, CS2 = (1.82 +/- 0.02) 10(-4) cm-1 HU-1 for Picker International scanner models 600SE and 1200SX, respectively. Direct measurements of CT numbers are compared with fitted results, providing a necessary preliminary steps in the development of objective CT interpretation. PMID- 2921969 TI - The effect of differences in data base on the determination of absorbed dose in high-energy photon beams using the American Association of Physicists in Medicine protocol. AB - Exposure rates were adjusted at the National Institute of Standards and Technology (NIST) on January 1, 1986 to take into account more recent values for some physical parameters, mainly in electron stopping power ratios. Exposure calibration factors for 60Co gamma rays Nx will therefore be lowered by 1.1%. Consequently, absorbed dose determinations in high-energy photon beams will be reduced by the same amount if the values for these physical parameters remain unchanged in the American Association of Physicists in Medicine (AAPM) protocol. If the same data base as used at NIST is applied in the AAPM protocol, then Ngas/Nx values, water-air stopping power ratios, and Pwall values will be different. The overall change in absorbed dose determinations using a consistent set of data will be a reduction of 0.8% for 60Co gamma rays and 1.5% for a 20-MV x-ray beam compared to the values before January 1, 1986. Since the net effect is small when different sets of data are applied, the new NIST exposure calibration factors may be used in combination with the AAPM protocol without significant error. PMID- 2921970 TI - A water phantom controller for automated acquisition of linac beam parameters. AB - Three-dimensional water phantoms are routinely used when acquiring the data necessary to commission medical linear accelerators. A new water phantom controller has been developed at our institution that is unique in several aspects. The water phantom controller is based on an IBM XT compatible computer. This has been interfaced to an Artronix three-dimensional water phantom and a commercially available linac setup controller. Some of the unique features of the new controller are (i) its ability to perform three-dimensional coordinate transformations on the fly (this removes the need to level and align the water tank with the beam axes and greatly reduces setup time). (ii) Its ability to communicate with a device which can control the linac operating parameters (this allows the water phantom controller to adjust, for example, the jaw size of the accelerator as it acquires data). (iii) Its ability to output the acquired data in a number of modes, including screen display, hardcopy plot, or disk file that may be transferred to a central treatment planning computer). (iv) Its ability to digitally process the acquired data. This water phantom controller may be used to gather machine data in a highly automated manner, greatly reducing the time required to gather the desired data. PMID- 2921971 TI - Determination of accurate dosimetric parameters for beveled intraoperative electron beam applicators. AB - Intraoperative electron beam therapy requires accurate dose maximum/monitor unit (Dmax/MU) values for both flat and beveled ended applicators (cones). Measurement of Dmax/MU values with either solid or nontilting scanning water systems may give rise to inaccuracies due to the difficulty in locating an accurate position for dmax, since the ionization chamber usually cannot be scanned along the central axis of the beveled intraoperative applicator. A linear one-dimensional scanner (which permits ionization measurements to be made as a function of water depth) has been modified to provide scanning along a line up to 30 degrees from the perpendicular to the phantom surface. This modification has proven helpful in improving the accuracy of certain dosimetric parameters (e.g., Dmax/MU) of beveled applicators. For example, we found inaccuracies which arose when we measured Dmax/MU of beveled intraoperative radiation therapy cones in either solid or other scanning water systems were greatly reduced, especially for the lower electron beam energies (e.g., 6 and 9 MeV). PMID- 2921972 TI - The use of storage phosphors for portal imaging in radiation therapy: therapists' perception of image quality. AB - Two drawbacks in quality of portal radiographs in radiation therapy are their low contrast and low spatial resolution. These are due to the low differential absorption of body tissues at therapeutic energies and to a relatively large radiation source. We used an experimental, high-contrast sensitivity storage phosphor imaging system (Eastman Kodak Co.) to produce portal images. The system consists of a storage phosphor detector, a high-contrast sensitivity laser scanner (12 bit), an image processing module, and a laser printer (12 bit). Patients undergoing radiation therapy treatments had both a conventional portal image and a storage phosphor image taken. Both were displayed side-by-side and were evaluated independently by three radiotherapists according to quality of information to verify the treatment field. Each of the three radiotherapists rated the storage phosphor images to be better (p less than 0.001) than the conventional images. However, rated improvements of low-contrast storage phosphor images of the pelvis and abdomen (40) were significantly lower than those of high contrast (head, neck, and chest) images (53). PMID- 2921973 TI - Dose delivery error detection by a computer-controlled linear accelerator. AB - A commercial dual photon energy, computer-controlled linear accelerator has a complex collimation and beam delivery system. For accurate dose delivery, six separate motorized elements must be properly positioned for a given beam selection. Experimentally instituted misalignments of the primary electron scattering foils, the primary collimator, the flattening filter, the scattering foil carousel, and the backscatter shield or shutter produced significant dose delivery errors. The ability of the Mylar window monitor chamber to detect these errors was examined for x-ray beams. The fault detection system failed to interrupt dose delivery in a number of situations where the error in dose per monitor unit delivered ranged from -6% to +270% of the calibrated value. PMID- 2921974 TI - Input of treatment planning data via a video frame grabber. AB - Video frame grabbers are powerful devices which perform rapid conversion of video images into digital format for subsequent computer processing. Recently, the cost of these devices has become competitive with sonic and magnetic digitizing tablets commonly used in radiation therapy treatment planning. Frame grabbers, plus all associated hardware/software can be interfaced to a variety of personal or microcomputers, and allow input of irregular treatment field and patient contour data into standard treatment planning systems. Such a system is described, which offers advantages of speed, accuracy, and resolution as compared to more conventional digitizing systems. PMID- 2921975 TI - Comments on "Image Feature Analysis and Computer-Aided Diagnosis in Digital Radiography. I. Automated Detection of Microcalcifications in Mammography". PMID- 2921976 TI - Comments on "Reference Dose Rates for Single- and Double-Plane 192Ir Implants". PMID- 2921977 TI - A generalized formulation of diffusion effects in micron resolution nuclear magnetic resonance imaging. AB - A generalized formulation of the diffusion related nuclear magnetic resonance (NMR) signal is derived from a random walk model. Previous analyses performed in the NMR spectroscopy were the formulations of the diffusion related signal amplitude at a specific time, such as the spin echo formation time. They are, in general, not applicable to continuous time domain analyses. In this paper, we have extended the theory to the two-dimensional imaging case and derived an analytical formula useful for the computation of the diffusion affected signal as a function of continuous time for a time variant gradient. This formulation will be useful in NMR imaging, especially in NMR microscopy where the diffusion associated signal attenuation is serious due to the strong gradient fields (100 1000 G/cm), and at the same time data are acquired continuously for the acquisition period. In addition to the loss of the resolution and signal-to-noise ratio due to the random phase fluctuation by diffusion, the variation of the intensity during the data acquisition period introduces a line broadening whose full width at half-maximum is found to be much larger than the bandwidth-limited resolution or diffusion related intrinsic resolution. This line spreading effect is integrated in a computer simulation and is evaluated as an integral part of the overall diffusion effects in micron resolution NMR imaging or NMR microscopy. PMID- 2921978 TI - Geometrical aspects of computed tomography: sensitivity profile and exposure profile. AB - A simple model has been developed for the generation of theoretical sensitivity and exposure profiles perpendicular to the tomographic plane in computed x-ray tomography. The model incorporates the functional dependence on scanner geometry, focal spot size and shape, and detector sensitivity. The sensitivity and exposure profiles are best depicted as the convolution of functions, when appropriately scaled, describing the focal spot intensity distribution and the transmittance of the pre- and postpatient collimators. Predictions of the model agree well with experimental results on both sensitivity and exposure profiles for small and large nominal slice thicknesses from five different computed tomography (CT) x ray systems. The CT x-ray systems selected represent both state of the art and older scanner models. Comparisons are also made on the degree of matching of the sensitivity and exposure profiles for each scanner which can be used as a measure of geometrical efficiency in the direction perpendicular to the tomographic plane. PMID- 2921979 TI - Determination of three-dimensional structure in biplane radiography without prior knowledge of the relationship between the two views: theory. AB - A novel method allows the determination of three-dimensional object structure from two projection images that are obtained at arbitrary, unknown orientations. Only minimal prior information concerning the imaging system is required. First, the image coordinates of eight or more object points that can be identified unambiguously in both views are used to determine the relative geometry of the two projections. Subsequently, the three-dimensional coordinates of the identified object points are determined, to within a scale factor, from the image coordinates of the points and the calculated imaging system geometry. A theoretical description of the overall method is provided, along with techniques for the reduction of effects of experimental errors and numerical errors that may arise in the course of the calculations. Methods to retrieve the absolute scale of the object are discussed also. PMID- 2921980 TI - Basic imaging properties of a computed radiographic system with photostimulable phosphors. AB - We measured the characteristic curve, modulation transfer function (MTF), and the Wiener spectrum of a commercially available computed radiographic (CR) system with photostimulable phosphor plate (imaging plate, IP). The characteristic curve (system response) obtained by an inverse-square x-ray sensitometry showed a wide dynamic range (order of 10(3) in maximum). The slit technique was employed to determine the MTF's, such as IP MTF, presampling MTF including the unsharpness of the detector (IP) and the blurring effect of the sampling aperture, and laser printer MTF. It was found that the MTF of the standard type of IP was comparable to that of medium-speed screen/film systems. The noticeable degradation of resolution in our CR system, however, occurred at the stage of image data sampling: the presampling MTF was inferior to the IP MTF due to the effect of the scattering and resultant spreading of the incidence laser beam and the emitted luminescence. The noise was characterized by means of digital Wiener spectrum using uniformly exposed noise data. Exposure ranges could be separated into different sections depending upon the noise sources, such as quantum mottle at low exposure and system structure noise at high exposure. PMID- 2921981 TI - Scientific basis of breast diaphanography. AB - Diaphanography, also known as transillumination, is a breast diagnostic technique based on differences in the diffuse transmittance of visible or near-infrared radiation. Previous papers by the authors reported on investigations of the effect of tumor size, depth at which the tumor is located, the thickness of the breast, and the effect of using photons of different wavelengths. The results from the study reported here indicate that absorption of light in hemoglobin is the basis for the luminance contrast, and shift in the infrared to red transmission ratio, in the diaphanographic image. Evidence is based on known extinction coefficients for oxyhemoglobin and deoxyhemoglobin as a function of wavelength, measurements of the transmitted spectrum in specimens, in vivo dual wavelength transillumination imaging of lesions containing different amounts of blood (bloody and clear cysts, hematomas, veins, fibroadenomas, and carcinomas), and comparison of preoperative diaphanographic images to blood vessel volumes measured by microscopic analysis of surgical specimens. Oxygenation affects the relative proportions of infrared and red light transmitted, but does not influence the diagnosis based on luminance contrast. PMID- 2921982 TI - Macroscopic dosimetry for radioimmunotherapy: nonuniform activity distributions in solid tumors. AB - In the context of radioimmunotherapy of cancer, there is a need for continued improvement of dosimetry of radionuclides localized in tumors. Current methods assume uniform distribution of radionuclides in the tumor despite experimental evidence indicating nonuniormity. We have developed a model in which nonuniform distribution of radioactivity in the tumor is taken into account. Spherically symmetric radionuclide distributions, depending linearly and exponentially on the radial position, are considered. Dose rate profiles in the tumor are calculated for potentially useful beta-emitting radionuclides, including 32P, 67Cu, 90Y, 111Ag, 131I, and 188Re, and for 193mPt, an emitter of conversion electrons and low-energy Auger electrons. For the radionuclide distributions investigated, high energy beta emitters, such as 90Y, are most effective in treating large tumors (diameter, d greater than approximately 1 cm), whereas for small tumors (d approximately 1 mm), medium energy beta emitters such as 67Cu are better suited. Very small tumors (d less than 1 mm), and micrometastases are best handled with low-energy electron emitters such as 193mPt. PMID- 2921983 TI - An energy sensitive cassette for dual-energy mammography. AB - A cassette for simultaneously acquiring dual-energy mammographic images is proposed and studied utilizing a theoretical noise analysis model. The cassette consists of a sandwich of two storage phosphor plates separated by a copper filter. The front, low atomic number, plate was assumed to be comprised of SrFBr and the rear, high atomic number, plate of commercially available BaFBr (98 mg/cm2 coating weight). Assuming a constant x-ray tube voltage of 50 kVp and a typical breast thickness, the theoretical model yielded a front SrFBr phosphor coating weight of approximately 21 mg/cm2. The study indicates that a relatively large separation in the average of x-ray photon energies absorbed in the two plates can be obtained. It also indicates that both a high-quality conventional (single energy) digital image and a tissue canceled digital image (i.e., a calcium image) can be obtained at dose levels comparable to those currently employed. The latter image could potentially improve the early detection of cancerous microcalcifications and also lends itself to computer aided diagnosis. PMID- 2921984 TI - Simulation studies of dual-energy x-ray absorptiometry. AB - Computer simulations were performed to predict the performance characteristics of dual-energy x-ray absorptiometry. K-edge filter techniques were analyzed in detail and compared to 153Gd sources in terms of output intensity, precision, patient dose, image contrast, beam hardening, and marrow fat effects. Similar analyses were performed for two dual-kV techniques that have been reported in the literature. The simulations indicate that K-edge filter techniques, or a dual-kV technique combined with K-edge filtering, can provide performance capabilities that equal or exceed those achievable with 153Gd systems. A (70/140) dual-kV technique with conventional (Al or Cu) filtration also has advantages in terms of source output intensity, but is 2-3 X inferior to the K-edge techniques and 153Gd in terms of patient dose and beam-hardening effects. PMID- 2921985 TI - Comparison of absorbed dose in bone substitute material and water using ionization measurements. AB - Absorbed dose in a liquid substitute for bone has been compared with absorbed dose in water for 9-, 12-, and 15-MeV electron beams using ionization chamber measurements. The ionization readings were converted to dose using collisional mass stopping power ratios. The collisional mass stopping powers for the liquid substitute of bone were calculated using the Monte Carlo Code PEGS4. The results of our study show that there is an increase in dose in the liquid bone substitute compared to water at shallow depths. The maximum increase in dose was 5%, 4%, and 2% at depths of 1.2, 1.5, and 2.0 cm, respectively, for 9-, 12-, and 15-MeV electrons. The density of the liquid bone substitute was 1360 kg/m3 and the effective atomic number was 11. PMID- 2921986 TI - Calibration frequency as determined by analysis of machine stability. AB - Simple statistical analysis is applied to the evaluation of the output measurements of equipment used in radiotherapy. The calibration frequency is calculated based on the stability of the equipment and the performance parameters required by the quality control criteria. PMID- 2921987 TI - A method of calculating the output factors of arbitrarily shaped electron fields. AB - It has been well demonstrated in the past that the dose output of an electron beam is highly dependent upon the design of the collimation system, the beam energy, and the field dimensions. Various approaches have been taken to calculate the output factor of an arbitrary rectangular beam. These methods, however, cannot be readily extended to accurately calculate the output factor of an irregular field. In this work, the output factor of an arbitrarily shaped electron field is calculated as the product of three terms: a weighting factor which is explicitly derived from a discrete electron pencil beam model, the known output factor of the regular electron field defined by an applicator or a set of trimmers from which the irregular field is formed, and a machine-dependent term which models the scatter contribution from the shielding. For the machine and fields of clinical interest discussed here, it was found that this latter term could be neglected; this may not be true in general. Results from this calculation are compared to measured data. PMID- 2921988 TI - Radiation probe for indirect evaluation of the high-voltage waveform of a Mo anode mammography unit. AB - A radiation probe was designed for indirectly determining the high voltage of a Mo anode mammography unit. The real time processing of the probe outputs yields exposure time, voltage waveform, kVp, and ripple in the range 24-40 kVp useful for screen-film mammography. The probe, connected to a portable computer, will be employed in a survey of radiation dose and image quality in mammography as part of an ongoing program in Italy. PMID- 2921989 TI - A fast low-noise line scan x-ray detector. AB - A fast, low-noise line scan detector (NIKOS) for digital radiography has been developed. It consists of an input x-ray phosphor screen that is coupled to a modified Reticon photodiode array by means of fiber optics with incorporated image intensifier. In its current version the detector can be operated with a maximum 500 Hz image acquisition rate for interlaced readout of two lines of 128 pixels each. Using a Gd2O2S:Tb x-ray input phosphor, an afterglow of 25% in the first subsequent readout was observed. We also conducted afterglow measurements on several other powder and single-crystal phosphors and the photodiode array. Using CdWO4, the afterglow of the detector is limited by the lag of the photodiode array of 4.5%. By modifying the readout electronics the noise of the photodiode array was reduced to below 1 Graylevel, corresponding to a signal-to noise ratio of 5200. The detective quantum efficiency (DQE) of the detector ranged from 0.18 to 0.4 for typical signal levels. The sensitivity was 10% saturation per 1.9 mR entrance dose. The modular design of the NIKOS detector allows for individual selection of each component to optimize performance for a given application. PMID- 2921990 TI - Neurogenetic diseases. PMID- 2921991 TI - [Free and sulfoconjugated plasma catecholamines in premature infants and mature newborn infants after birth]. AB - Sulfate conjugation represents a major pathway for the inactivation of free catecholamines. We investigated the ability of newborns to protect the body against an overflow of free catecholamines by sulfoconjugation. No difference of free catecholamines in the umbilical artery was found in preterm and term newborns. Furthermore, preterm and term newborns were able to form sulfoconjugated catecholamines. In term newborns, but not in preterm newborns, there was a significant relationship between free catecholamines and their respective sulfoconjugated forms (p less than 0.001). In comparison to term infants sulfoconjugated dopamine and norepinephrine were significantly decreased in preterm newborns, although the placental extraction rates of these catecholamines were markedly lower in preterm infants. This favors the conclusion, that synthesis rather than increased degradation may be responsible for the low levels of sulfoconjugated catecholamines in preterm infants. Thus, preterm newborns might be less able to inactivate free catecholamines by sulfoconjugation. The clinical importance of these results concerning treatment of preterm newborns with dopamine and noradrenaline has yet to be established. PMID- 2921992 TI - [The left ventricular functional parameter in M-mode echocardiography in various administration rates of a loading dose of theophylline in premature infants]. AB - The aim of study was to show a positive effect of theophylline on the cardiac pump function immediately after i.v. bolus injection of the loading dose. Therefore we recorded m-mode echocardiograms before and immediately after bolus injection (over 2-3 min) of 6 mg/kg theophylline. On studying 12 preterm infants we observed a reduction of the left ventricular shortening fraction and circumferential shortening velocity. In the second part of the study we administered the same dose of theophylline over a period of 20 min. No significant differences in m-mode echocardiographic parameters before and after infusion were seen. We attribute these results to incalculable effects of theophylline preload, wall distension, and afterload. Nonetheless slow application of theophylline loading dose is recommended in preterm infants. PMID- 2921993 TI - [The causes of short stature in children in ambulatory care]. AB - The data relating to all children referred over a 10-year period to the out patient department of a children's hospital in a West German city because of growth retardation were retrospectively analyzed. A diagnosis of short stature was made in 306 patients. The proportion of boys to girls was 2.5:1. The average age of the patients was about 10 years (0.75-17.4); 9.8% of the children were less than 4 years old, and 5.9% were over 16 years. In 68.3% of the patients the Study revealed constitutional delay of growth or familial short stature or a combination of two. Twelve children (3.9%) were demonstrated to have growth hormone deficiency. PMID- 2921994 TI - [The prognosis of the very small premature infant. Catamnestic studies of premature infants with a birth weight up to 1,000 grams]. AB - 29 of 50 premature infants with a birth weight up to 1,000 g survived and were examined between 2-9 years of age. 13 children showed no or only minimal abnormalities. 11 children were felt to require treatment but to have a good prognostic outcome. 3 children had multiple disabilities. From the total of 16 children requiring treatment only 5 were under treatment before our evaluation. The quality of life is good for 24 of the 29 survivors. PMID- 2921995 TI - [Respiratory insufficiency in mucoviscidosis. Pathophysiologic aspects of conservative drug therapy]. AB - The compensated chronic respiratory acidosis in a girl with cystic fibrosis changed into a mixed respiratory acidosis and metabolic alkalosis under the influence of therapeutic measures. As a consequence respiratory insufficiency worsened. Conservative management of the alkalosis alone both improved hypoxemia and hypercapnia without needing artificial ventilation. PMID- 2921996 TI - Histidine modulates the clastogenic effect of oxidative stress. AB - The kinetics of the formation of single-strand breaks induced by H2O2 in DNA is more rapid in Eagle's Modified Minimal Essential Medium (MEM) than in phosphate buffered saline (PBS). Among the components of MEM, we found that histidine increases the rate of degradation of DNA by H2O2 in PBS dose-dependently. In hamster lung fibroblasts histidine increases the cytotoxicity of H2O2, as well as the number of sister-chromatid exchanges and the frequency of micronuclei induced by hydrogen peroxide. PMID- 2921997 TI - Variability of the adaptive response to ionizing radiations in humans. AB - Human lymphocytes exposed to low doses of ionizing radiations from incorporated tritiated thymidine ([3H]dThd) or from X-rays become less susceptible to the induction of chromatid aberrations by high doses of X-rays. This indicates that low doses of ionizing radiation can produce an effect similar to the adaptive response observed with alkylating agents in prokaryotes, animal and plant cells. To determine whether there is individual variability in the adaptive response to ionizing radiations we exposed human lymphocytes from 18 different healthy donors to 'adapting' doses of [3H]dThd (0.01 microCi/ml) or X-rays (0.01 Gy) and subsequently to a 'challenge' treatment of 0.75 Gy of X-rays delivered 2 h before fixation. Four of the 18 donors did not show an adaptive response; in some cases in these individuals a synergistic response of increased, rather than decreased, damage was found. Two of these 4 donors showed no adaptive response in 3 subsequent experiments separated by 4-month intervals. This suggests that the human population exhibits a heterogeneity in the adaptive response to ionizing radiations which might be, at least in part, genetically determined. PMID- 2921998 TI - Clastogenic effects of cis-diamminedichloroplatinum. I. Induction of chromosomal aberrations in somatic and germinal cells of mice. AB - The clastogenicity of cisplatin, cis-diamminedichloroplatinum(II), an extensively used antitumor drug, has been studied employing (101/E1 X C3H/E1)F1 mice, aged 12 14 weeks. Chromosomal aberrations were assessed in mitotic divisions of bone marrow cells and differentiating spermatogonia. The drug was tested at 3 doses, 0.5, 1.0 and 2.5 mg/kg and 1.0, 2.5 and 5.0 mg/kg, respectively, for bone marrow and spermatogonia. Cisplatin had a clastogenic effect which was dose-dependent in both cell types. The frequencies of aberrant cells increased non-linearly in bone marrow and the dose-response relationship could be best described by a linear quadratic equation. At the highest dose the affected cells carried multiple aberrations. An average of 2.7 aberrations per aberrant cell was observed 12 h after treatment of the mice with 2.5 mg/kg of cisplatin. In differentiating spermatogonia the dose response for aberrant cells could be described by a linear equation. The damage to the individual affected cell was less dramatic than in bone marrow, averaging 1.4 aberrations per damaged cell at the highest dose tested. Gaps were excluded from these considerations but they generally also showed a dose-related increase. A quantitative comparison of the clastogenic response to cisplatin was based on the dose-response relationships using 2 criteria, the doubling dose and the dose of unit increase (DUI). For both comparisons the general conclusion was that bone marrow cells were twice as sensitive as differentiating spermatogonia to the clastogenic action of cisplatin. PMID- 2921999 TI - 4-Quinolone antibiotics: positive genotoxic screening tests despite an apparent lack of mutation induction. AB - The effects of different 4-quinolone antibiotic derivatives (4-Qs) in a number of short-term tests commonly employed for the evaluation of genetic toxicity were studied. Incorporation of [3H]thymidine into mitogen-stimulated peripheral blood lymphocytes was strongly enhanced at a low concentration (1.56 micrograms/ml) for most of the tested 4-Qs, whereas DNA strand breakage in lymphoblastoid cells was evident only for ciprofloxacin (10 micrograms/ml and upwards), ofloxacin (80 micrograms/ml) and norfloxacin (160 micrograms/ml). Ciprofloxacin induced a significant amount of unscheduled DNA synthesis, but was found to be negative in a shuttle vector plasmid mutation test. Ciprofloxacin (80 micrograms/ml) did not inhibit enzymes involved in the early steps of pyrimidine biosynthesis. Cell growth was slightly depressed at a concentration of 20 micrograms/ml, becoming marked at 80 micrograms/ml. In conclusion, this study seeks to contribute to an improved evaluation of genotoxic screening test data, by focusing attention on the conflicting effects imposed by the 4-Qs on a battery of such tests. PMID- 2922000 TI - Identification of ataxia telangiectasia heterozygotes by flow cytometric analysis of X-ray damage. AB - Flow cytometry was used to identify heterozygotes for the autosomal recessive DNA repair deficiency disease ataxia telangiectasia (AT). Confluent G0/G1 fibroblasts from 4 homozygotes (at/at), 5 obligate heterozygotes (at/+) and 7 presumed normal controls (+/+) were X-irradiated with 200 Rad and subcultured immediately in medium containing 5-bromodeoxyuridine (BrdU). Cells were harvested 72 h later and stained with fluoresceinated anti-BrdU antibody to identify cells that had entered S phase. They were counterstained with propidium iodide to measure total DNA content. On the basis of relative release from G0/G1, the at/+ strains as a group (33 +/- 3% release) were distinguished from both the presumed +/+ strains (60 +/- 3%) and at/at strains (85 +/- 3%), although the individual values for some strains did show overlap between genotypes. When 10 cell strains were coded and analyzed in 'blind' experiments, all 4 heterozygotes were correctly assigned, although one poorly growing presumed normal line was incorrectly assigned as a heterozygote. By a similar assay in which exponentially growing cultures were pulsed briefly with BrdU 8 h after irradiation with 400 Rad and then harvested immediately, presumed +/+ cells as a group could be distinguished from at/at cells but not from at/- cells. This combination of assays assists in the identification of all 3 AT genotypes. This should be of both basic and diagnostic use, particularly in families known to segregate AT. PMID- 2922001 TI - Flow cytometric analysis of X-ray sensitivity in ataxia telangiectasia. AB - Flow cytometric analysis of 5-bromodeoxyuridine (BrdU) incorporation during DNA synthesis was used to characterize the effects of X-rays on cell-cycle kinetics in the DNA-repair deficiency disease ataxia telangiectasia (AT). Cultured fibroblasts from homozygotes (at/at), heterozygotes (at/+) and normal controls (+/+) were either: (1) irradiated, cultured, then pulsed with BrdU and harvested, or (2) pulsed with BrdU, irradiated, cultured and then harvested. Cells were then fixed and stained with both a fluoresceinated monoclonal antibody against BrdU to identify S-phase cells and with propidium diiodide to measure total DNA content. Irradiation of +/+ and at/+ cells induced a similar, transient G2/M arrest detectable within 8 h, which subsequently delayed by 6-8 h the passage of cells into G1 and depleted early S phase. In contrast, at/at cells failed to arrest in G2/M phase and entered the next cell cycle without pausing to repair radiation induced damage. X-Rays also blocked entry of +/+ G1 cells into S phase, subsequently reducing the total S-phase population. This effect was not observed in at/at cells. These cell-cycle responses to radiation may be of diagnostic use and ultimately may help explain the basic defect in AT. PMID- 2922002 TI - Adaptive response of human lymphocytes to low-level radiation from radioisotopes or X-rays. AB - Human peripheral blood lymphocytes stimulated in vitro were exposed to low level irradiation ('adaptive dose') from radioisotopes ([3H]dThd, [14C]dThd, HTO and 32P). After 50 h in culture, they were irradiated with 50 rad of X-rays ('challenge dose') and fixed 3 h later. In another series, the lymphocytes received an adaptive dose of 5 rad of X-rays at 32 h after stimulation and a challenge dose of 150 rad at 48 h; the cells were fixed at 54 h. In cells that received both the adaptive and challenge doses, the frequencies of chromosomal aberrations (chromatid and isochromatid deletions) were lower than expected on the basis of additivity of the effects of the individual treatments. These results support those published from Wolff's laboratory in showing that human lymphocytes can become 'adapted' by prior exposure to low level irradiation so that they become less sensitive to the chromosome-breaking effects of X-rays delivered subsequently. The magnitude of reduction in frequencies in the 'adapted' cells, however, varied between the blood samples from different donors. PMID- 2922003 TI - Induction of sister-chromatid exchanges by direct and indirect mutagens in human lymphocytes, co-cultured with intact rat liver cells. Effect of enzyme induction and preservation of the liver cells by freezing in liquid nitrogen. AB - An in vitro assay system using intact rat hepatocytes and human peripheral lymphocytes is described which has been developed with the aim of bringing test conditions closer to in vivo conditions, thereby broadening the available battery of simple in vitro assays. A culture vessel, which contains an inner chamber with a semipermeable bottom, has been designed to allow easy removal of the hepatocytes. Determination of sister-chromatid exchange rate was used as the experimental end point. For validation, a series of chemicals were used which have been tested previously in a large interlaboratory investigation of short term test methods. Our study supplies complementary information to this investigation in as much as some chemicals could be correctly assigned as positive or negative, in contrast to what was found in the earlier tests. Furthermore, we show that the metabolic capacity of both normal and induced liver cells can be preserved in liquid nitrogen for long periods. PMID- 2922004 TI - Cytogenetic effects of fenvalerate in mammalian in vivo test system. AB - A synthetic pyrethroid insecticide, fenvalerate, was tested for its cytogenetic effects in the mouse in vivo test system at 100, 150 and 200 mg/kg. Bone marrow metaphase analysis revealed significant increases in chromosomal aberrations in the groups treated with 150 and 200 mg/kg by intraperitoneal injection. In the micronucleus test the occurrence of PCEs with MN marginally increased with dose. Induction of PCEs with MN was significant over control again with the higher two doses. Incidence of sperm abnormalities slightly increased with dose but a significant increase was noted in all treated series over control. PMID- 2922005 TI - The release of mutagens from airborne particles in the presence of physiological fluids. AB - Airborne particulates collected indoors in residences and outdoors were extracted by soxhlet extraction and sonication with methanol. In a comparative study in which mutagenic activity was evaluated in the Salmonella typhimurium reversion assay both soxhlet extraction and sonication proved to be suitable extraction methods. First, the residue, obtained by sonication of loaded filters with methanol followed by evaporation to dryness (tar), was sonicated with newborn calf serum and lung lavage fluid from pigs. All serum extracts of the tar were mutagenic to Salmonella typhimurium TA98, and contained direct- and indirect acting mutagens. However, the mutagenic activity recovered by serum was only about half of the total mutagenic activity of the tar. The other part of the mutagenic activity remained in the tar. Lung lavage fluid was only able to remove 5-10% of direct-acting mutagens from the tar of all samples. About 20% of indirect-acting mutagens from indoor air were recovered in lung lavage fluid, while the lung lavage fluid extract from outdoor air did not show indirect mutagenic activity. Second, mutagenic activity recovered by direct sonication of the filters with physiological fluids was comparable with the recovery obtained by sonication of the tar. However, after sonication of the filter with lung lavage fluid hardly any mutagenic activity remained on the filter, whereas after sonication of the tar a clear mutagenic activity was observed in the non-soluble residue. PMID- 2922006 TI - Increased frequency of sister-chromatid exchange induced by dothistromin in CHO cells and human lymphocytes. AB - Dothistromin is a metabolite produced by Dothistromin pini and Cercospora arachidicola. The latter fungus is a pathogen of the peanuts and thus the mycotoxin may be a contaminant of foodstuffs. Dothistromin induces a dose dependent increase in sister-chromatid exchange frequency in Chinese hamster ovary cells and stimulated human lymphocytes. The increased frequency in human lymphocytes seen with dothistromin is significantly higher among lymphocytes from smokers compared with those from non-smokers. PMID- 2922007 TI - The Computerized Laboratory Notebook concept for genetic toxicology experimentation and testing. AB - We describe a microcomputer system utilizing the Computerized Laboratory Notebook (CLN) concept developed in our laboratory for the purpose of automating the Battery of Leukocyte Tests (BLT). The BLT was designed to evaluate blood specimens for toxic, immunotoxic, and genotoxic effects after in vivo exposure to putative mutagens. A system was developed with the advantages of low cost, limited spatial requirements, ease of use for personnel inexperienced with computers, and applicability to specific testing yet flexibility for experimentation. This system eliminates cumbersome record keeping and repetitive analysis inherent in genetic toxicology bioassays. Statistical analysis of the vast quantity of data produced by the BLT would not be feasible without a central database. Our central database is maintained by an integrated package which we have adapted to develop the CLN. The clonal assay of lymphocyte mutagenesis (CALM) section of the CLN is demonstrated. PC-Slaves expand the microcomputer to multiple workstations so that our computerized notebook can be used next to a hood while other work is done in an office and instrument room simultaneously. Communication with peripheral instruments is an indispensable part of many laboratory operations, and we present a representative program, written to acquire and analyze CALM data, for communicating with both a liquid scintillation counter and an ELISA plate reader. In conclusion we discuss how our computer system could easily be adapted to the needs of other laboratories. PMID- 2922008 TI - DNA adduct formation, metabolism, and morphological transforming activity of aceanthrylene in C3H10T1/2CL8 cells. AB - Aceanthrylene (ACE), a cyclopenta-fused polycyclic aromatic hydrocarbon (CP-PAH) related to anthracene, has been studied for its ability to be metabolized, to form DNA adducts, and to morphologically transform C3H10T1/2CL8 mouse embryo fibroblasts in culture. Although ACE has been previously shown to be a strong mutagen in Salmonella typhimurium strains TA89 and TA100, it did not transform C3H10T1/2 cells (0.4-16 micrograms/ml) under 2 treatment protocols: treatment (for 24 h) 1 day after seeding the cells; treatment (for 24 h) 5 days after seeding the cells. Both protocols are effective in detecting the morphological transforming activity of PAH and CP-PAH and the latter protocol has been shown to be effective in detecting chemicals which are active in the first protocol only with the additional treatment of the cells with a tumor promoter. ACE is metabolized by C3H10T1/2 cells to ACE-1,2-dihydrodiol (the cyclopenta-ring dihydrodiol) at a rate of 450 pmoles ACE-1,2-dihydrodiol formed/h/10(6) cells. ACE-7,8-dihydrodiol and ACE-9,10-dihydrodiol, identified as major Aroclor-1254 induced rat liver microsomal metabolites from their UV, NMR, and mass spectral data, were not identified in incubations of C3H10T1/2 cells with ACE. ACE-DNA adducts in C3H10T1/2 cells were isolated, separated, identified, and quantitated using the 32P-postlabeling method. ACE forms 4 major adducts and each was identified as an ACE-1,2-oxide/2'-deoxyguanosine adduct. The level of adduction was 2.18 pmoles ACE adducts/mg DNA after a 24-h incubation of ACE (16 micrograms/ml) with C3H10T1/2 cells. ACE-DNA adduct persistence and repair were evaluated in C3H10T1/2 cells using a hydroxyurea block after ACE treatment. ACE DNA adducts were not repaired under the conditions used in the morphological transformation studies. Thus, ACE provides an interesting example of a mutagenic PAH which is metabolized by C3H10T1/2 cells to active intermediates, forms relatively stable and persistent 2'-deoxyguanosine adducts in C3H10T1/2 cells, and yet induces no detectable morphological transforming activity under the experimental conditions used. PMID- 2922009 TI - Chromosome aberrations induced by aflatoxin B1 in rat bone marrow cells in vivo and their suppression by green tea. AB - Aflatoxin B1 (AFB1)-induced chromosome aberrations (CA) in rat bone marrow cells consisted mainly of gaps and breaks. Cells with exchanges and multiple CA were observed infrequently. The incidence of aberrant cells and the number of aberrations per cell were at their maximum levels 18 h after the AFB1 injection. They were dependent on the administered dose of AFB1. Rats given the hot water extract from green tea (GTE) 24 h before they were injected with AFB1 displayed considerably suppressed AFB1-induced CA in their bone marrow cells. Rats administered GTE 2 h before or after the AFB1 injection showed no suppressive effect. The suppressive effect of GTE on AFB1-induced CA paralleled the dose of GTE when given in the range between 0.1 and 2 g/kg body weight; higher doses produced no additional suppression. On the other hand, rats given the hot water extract from black tea or coffee 24 or 2 h before the AFB1 injection showed no suppressive effect. The administration of caffeine 24 h before the AFB1 injection suppressed AFB1-induced CA as well as the administration of caffeine 2 h before the AFB1 injection. However, the suppression rate with 2 h was larger than with 24 h. The suppression by ellagic acid was found only when it was given 2 h before the AFB1 injection. The administration of ascorbic acid or tannic acid did not significantly suppress AFB1-induced CA. The tannin mixture extracted from green tea (GTTM) showed a similar tendency to GTE, that is, the administration of GTTM 24 h before the AFB1 injection potently suppressed AFB1-induced CA, while the administration of GTTM 2 h before the AFB1 injection did not suppress them significantly. The suppressive effect of GTTM on AFB1-induced CA paralleled the dose of GTTM when given in the range of 75-450 mg/kg body weight. PMID- 2922010 TI - A comparison of sister-chromatid exchange in mouse peripheral blood lymphocytes exposed in vitro and in vivo to phosphoramide mustard and 4 hydroxycyclophosphamide. AB - Cyclophosphamide (CP) and two of its known metabolites, 4-hydroxycyclophosphamide (4-OHCP) and phosphoramide mustard (PAM), were analyzed for their ability to induce sister-chromatid exchanges (SCEs) in mouse peripheral blood lymphocytes (PBLs) in vitro and in vivo. At equimolar concentrations, CP is a more potent SCE inducer in vivo than PAM and PAM and 4-OHCP induce equal numbers of SCEs in a dose-dependent manner. The present study also shows that these metabolites of CP are more potent SCE inducers than CP itself in vitro. This relationship might be explained by the differences in pharmacokinetics of these compounds. PMID- 2922011 TI - Sister-chromatid exchanges in lymphocytes of workers exposed to trichloroethylene. AB - To detect mutagenic effects of trichloroethylene (TCE) on humans, sister chromatid exchanges (SCEs) were analyzed in lymphocytes of 22 workers occupationally exposed to TCE and 22 matched controls. Although urinalysis in the workers revealed their obvious exposure to TCE, no increase in SCE frequencies was found in lymphocytes of the workers. SCE analysis in lymphocytes could not detect mutagenic effects by occupational exposure to TCE on humans. PMID- 2922012 TI - Enhancement of benzene clastogenicity by praziquantel in mice. AB - Praziquantel (PQ) is a commonly used drug to treat patients with schistosomiasis. Previous studies using cells in vitro have shown that PQ can enhance the mutagenic activities of known mutagens. We have conducted a cytogenetic - urine metabolite study to determine the in vivo clastogenic and co-clastogenic potential of PQ with a ubiquitous environmental contaminant, benzene (BZ). 16 groups of adult male ICR mice (5 animals per group) were used. They were negative control, solvent controls (cremophore E1 3%, olive oil and combined), positive control (BZ 440 mg/kg b.w.) and 11 exposed groups. To test for clastogenicity of PQ, mice were treated orally with 100, 400, 800 and 1200 mg/kg b.w. PQ and sacrificed 30 h later for determination of micronuclei (MN) frequency in bone marrow polychromatic erythrocytes (PCE). None of these PQ does induced an increase of MN frequency. On the other hand, BZ induced, as expected, a high frequency of MN (46.4 +/- 6.34/1000 PCE). The enhancement effect of PQ was tested in 7 groups of mice using 3 different protocols. Mice were treated with 440 mg/kg b.w. BZ and 1 h later with 0, 100, 200, 400, 800 and 1200 mg/kg b.w. PZ. In another group, 800 mg/kg PQ was administered at 3 h after BZ exposure. In the last group, PQ (800 mg/kg) was administered at 1 h prior to BZ exposure. Results from the first combined exposure group showed a significant PQ dose-dependent increase in the frequency of MN in PCE (p less than 0.05). The increase with the two high doses of praziquantel is significantly higher (p less than 0.05) than the MN frequencies in the benzene control and the expected value based on the additive effects of the two agents. Studies with other combined treatment groups showed that the induction of MN was highest when PQ was administered at 1 h before BZ exposure. Moreover, the presence of BZ metabolites (muconic acid, phenol, catechol and hydroquinone) in urine was studied in 6 of the combined treatment groups. This metabolite study revealed that PQ enhanced the metabolism of BZ towards the pathway to form muconaldehyde which is converted to muconic acid in urine. In conclusion, our study showed that PQ is not a clastogen but can enhance the clastogenic activity of BZ in vivo by shifting the metabolic pathways of BZ towards formation of muconaldehyde which may be responsible for the enhancement effect. PMID- 2922013 TI - The prevention of benzene-induced genotoxicity in mice by indomethacin. AB - Benzene is a myelotoxin which affects hemopoietic progenitor cells leading to bone-marrow depression as well as a genotoxin which causes chromosomal abnormalities including micronucleus formation. We have demonstrated previously that benzene administered to DBA/2 or C57B1/6 mice causes bone-marrow depression and increased prostaglandin E2 levels in bone marrow; both of these effects can be prevented by the coadministration of indomethacin, a selective inhibitor of prostaglandin synthase. We report, herein, that benzene (400-600 mg/kg body weight), under conditions where it depresses bone-marrow cellularity, also induces an increase in the frequency of micronucleus formation in polychromatic erythrocytes of C57B1/6 mice which is also prevented by the coadministration of indomethacin at levels that do not inhibit cytochrome P450 or myeloperoxidase. In Swiss Webster wild-type mice doses of benzene from 400 to 1000 mg/kg were without effect on marrow cellularity, but did induce the formation of micronucleated polychromatic erythrocytes which could be prevented by indomethacin. In contrast, DBA/2 mice, a strain highly sensitive to benzene, exhibited significant bone marrow depression at a dose of benzene of 100 mg/kg body weight. Even at this low dose, benzene is too toxic toward developing erythrocytes to allow the evaluation of micronucleus formation. The frequency of induction of micronucleated polychromatic erythrocytes by benzene thus depends on the strain of mouse used. Furthermore, micronucleus formation appears to be an early and very sensitive indicator of benzene toxicity. A possible role for prostaglandin H synthase in the geno- and myelo-toxicity of benzene is discussed. PMID- 2922014 TI - Renal insufficiency in treated essential hypertension. AB - We analyzed the clinical courses of 94 patients with treated primary hypertension and initially normal serum creatinine concentrations (less than or equal to 133 mumol per liter [less than or equal to 1.5 mg per deciliter]) who were followed for a mean (+/- SD) of 58 +/- 34 months (range, 12 to 174) to determine the frequency with which renal function deteriorated and the factors associated with deterioration. Fourteen patients (15 percent) had an increase in serum creatinine concentrations (greater than or equal to 35 mumol per liter [greater than or equal to 0.4 mg per deciliter]); in 16 percent of the 61 patients with apparently good control of blood pressure, the serum creatinine concentration rose 59 +/- 33 mumol per liter (0.67 +/- 0.38 mg per deciliter). Despite good control of diastolic blood pressure (less than or equal to 90 mm Hg), black patients were twice as likely as white patients to have elevations in serum creatinine (23 percent vs. 11 percent). Stepwise discriminant function analysis showed that a significant rise in the serum creatinine concentration was most likely to occur in association with older age, black race, a higher number of missed office visits, and employment as a laborer. We conclude that although renal function was preserved in 85 percent of patients with treated hypertension, it may deteriorate in some patients despite good blood-pressure control. Our observations may partly explain why hypertension, particularly among black persons, remains a leading cause of renal disease in the United States. PMID- 2922015 TI - The physician factor in cesarean birth rates. AB - To investigate the influence of physicians' practice styles on the rate of deliveries by cesarean section, we studied 1533 affluent women at low risk of obstetrical complications who were cared for by 11 obstetricians in a single community hospital. The mean rate of delivery by cesarean section was 26.9 percent, but the rate ranged from 19.1 to 42.3 percent, according to the physician. The mean rate of primary cesarean section (i.e., the rate for women without previous cesarean deliveries) was 17.2, with a range of 9.6 to 31.8 percent. A stepwise logistic-regression model of the determinants of primary cesarean section, including the individual physician, parity, birth weight, and maternal age and excluding specific medical indications, showed that only nulliparity (P less than 0.0001) was more important than the identity of the physician (P less than 0.001) in its influence on the rate of cesarean section. Variation in cesarean-section rates among physicians was not attributable to the practice setting, the patient population, the degree of obstetrical risk, or the physician's recent medicolegal experience, and it was not accompanied by corresponding differences in neonatal outcome. We conclude that individual practice style may be an important determinant of the wide variations in the rates of cesarean delivery among obstetricians. Our data do not permit us to say with certainty whether the procedure is overused by some obstetricians or underused by others, but we found no obvious differences in neonatal outcome associated with differences in the cesarean-section rate. PMID- 2922016 TI - Inotropic therapy for heart failure: paradise postponed. PMID- 2922017 TI - The kidney in hypertension--villain and victim. PMID- 2922018 TI - Bulimia nervosa. PMID- 2922019 TI - The prevalence of anorexia nervosa. PMID- 2922020 TI - Polycystic kidney disease. PMID- 2922021 TI - Right renal trauma: a side effect of biliary lithotripsy. PMID- 2922022 TI - Valvular heart disease in systemic lupus erythematosus. PMID- 2922023 TI - Transmission of infectious agents by inadequately sterilized ENT instruments. PMID- 2922024 TI - Eye injuries to football players. PMID- 2922025 TI - Medical advice by celebrities. PMID- 2922026 TI - Efficacy of neonatal ocular prophylaxis for the prevention of chlamydial and gonococcal conjunctivitis. AB - Opinions differ concerning the efficacy of prophylaxis against neonatal chlamydial and gonococcal conjunctivitis. From January 1986 through June 1988, we gave all infants born at Kings County Hospital Medical Center one of three prophylactic agents -- silver nitrate drops, erythromycin ophthalmic ointment, or tetracycline ophthalmic ointment. The treatments were rotated monthly. Gonococcal ophthalmia occurred in 8 of the 12,431 infants born during the study (0.06 percent), 1 in the silver nitrate group, 4 in the erythromycin group, and 3 in the tetracycline group (P not significant). Seven of these infants were born to women who had received no prenatal care. From September 1985 through December 1987, we screened 4357 pregnant women for cervical chlamydial infection, of whom 341 (8 percent) had positive cultures. Of their offspring, 230 were evaluated for neonatal chlamydial conjunctivitis; the incidence was 20 percent in the silver nitrate group, 14 percent in the erythromycin group, and 11 percent in the tetracycline group (P not significant). We conclude that neonatal ocular prophylaxis with either erythromycin or tetracycline ophthalmic ointment does not significantly reduce the incidence of chlamydial conjunctivitis in the offspring of mothers with chlamydial infection as compared with silver nitrate, and that better management of maternal chlamydial infection is therefore required. We also conclude that there is a small but appreciable incidence of neonatal gonococcal ophthalmia that could be prevented by better prenatal screening and treatment of maternal gonococcal infection. PMID- 2922028 TI - Why we need a program for the control of Chlamydia trachomatis. PMID- 2922027 TI - Association of the Lewis blood-group phenotype with recurrent urinary tract infections in women. AB - Blood-group antigens are found on the surface of urothelial cells and may affect bacterial adherence and thereby the susceptibility to urinary tract infection. We determined the ABO, P, and Lewis blood-group phenotypes in 49 white women with histories of recurrent urinary tract infections and compared them with those found in 49 healthy control women without recurrent urinary tract infections. There was no significant difference between the two groups in the distribution of the ABO or P phenotypes. The distribution of Lewis blood-group phenotypes among control women was similar to that in the general population: secretor phenotype (Le(a-b+)), 74 percent; nonsecretor phenotype (Le(a+b-)), 18 percent; and recessive phenotype (Le(a-b-)), 8 percent. The following distribution was noted among the women with recurrent urinary tract infections: secretor phenotype, 45 percent; nonsecretor phenotype, 29 percent; and recessive phenotype, 26 percent (P = 0.002). When the women with nonsecretor and recessive phenotypes were combined and considered collectively, the odds ratio (an estimate of relative risk of recurrent urinary tract infection) for those without the secretor phenotype was 3.4 (95 percent confidence interval, 1.5 to 7.9). We conclude that there is an increased frequency of the Lewis blood-group nonsecretor (Le(a+b-] and recessive (Le(a-b-] phenotypes among women with recurrent urinary tract infections. PMID- 2922029 TI - Chlamydia trachomatis pneumonia in an HIV-seropositive patient. PMID- 2922030 TI - Changes in needle sharing and syringe cleaning among San Francisco drug abusers. PMID- 2922031 TI - Amplification of DNA from epithelial cells in urine. PMID- 2922032 TI - Chromosome analyses from urinary sediment: postnatal confirmation of a prenatally diagnosed trisomy 20 mosaicism. PMID- 2922033 TI - Insertion of umbilical arterial catheters with guidance by ultrasound. PMID- 2922034 TI - Yersinia enterocolitica serotype O:3 sepsis after blood transfusion. PMID- 2922035 TI - Glycogen storage disease associated with Niemann-Pick disease. PMID- 2922036 TI - Is extracorporeal biliary lithotripsy painless? My experience with three shock wave sources. PMID- 2922037 TI - Changes in misconduct investigation planned. PMID- 2922038 TI - Legacy of Three Mile Island. PMID- 2922039 TI - Veterinary science. Plan to close schools resisted. PMID- 2922040 TI - Mental health. Sterilization protests. PMID- 2922041 TI - Plagiarism dispute. Clinical researchers at odds. PMID- 2922042 TI - Risks from ionizing radiation. AB - For the public in the United Kingdom--and the United States--natural radon is a far greater radiation hazard than are emissions from nuclear installations. PMID- 2922043 TI - Human immunodeficiency virus. Revving up gene expression. PMID- 2922044 TI - Cell motility. Networks from mutants. PMID- 2922045 TI - Designer catalytic antibodies. PMID- 2922046 TI - Daedalus. New eyes for old. PMID- 2922047 TI - Distemper virus in Baikal seals. PMID- 2922048 TI - 'Amylin' hormone. PMID- 2922049 TI - On the SCIDs? PMID- 2922050 TI - Structure of tumour necrosis factor. AB - Tumour necrosis factor is a trimeric molecule, each subunit of which consists of an antiparallel beta-sandwich. Individual subunits from the trimer by a novel edge-to-face packing of beta-sheets. A comparison of the subunit fold with that of other proteins reveals a remarkable similarity to the 'jelly-roll' structural motif characteristic of viral coat proteins. PMID- 2922051 TI - A laminin-like adhesive protein concentrated in the synaptic cleft of the neuromuscular junction. AB - A striking example of topographic specificity in synapse formation is the preferential reinnervation of original synaptic sites on denervated muscle fibres by regenerating motor axons. This specificity is mediated by the basal lamina of the synaptic cleft. A glycoprotein, s-laminin, has now been identified that is selectively associated with synaptic basal lamina and is recognized by motoneurons. Molecular cloning reveals that s-laminin is a novel homologue of laminin, a potent promoter of neurite outgrowth. PMID- 2922052 TI - Incubation period of AIDS in San Francisco. AB - In a closed population, the distribution of AIDS diagnoses over time is the convolution of the distributions of human immunodeficiency virus (HIV) infections and the incubation period. This has motivated estimates of the infection distribution, assuming known diagnosis and incubation distributions, but the usefulness of this method is limited by uncertainty about incubation. The large amount of information on the distribution of HIV infections in San Francisco's gay community suggests the opposite approach--estimating the incubation distribution, assuming known infection and diagnosis distributions. A non parametric implementation of this strategy produced an estimate with a median at 9.8 years, increasing hazard rates, and less uncertainty than previous estimates. PMID- 2922053 TI - A new strategy for the generation of catalytic antibodies. AB - The high binding affinity and specificity of antibodies for a wide range of ligands has recently been exploited in the generation of catalysts for acyl transfer reactions, carbon-carbon bond forming and carbon-carbon bond cleaving reactions. In addition, a number of strategies are emerging for the generation of catalytic antibodies including transition state stabilization, catalysis by approximation, and the introduction of catalytic groups or cofactors into antibody combining sites. An important goal in the design of catalytic antibodies is the development of general rules relating hapten structure to the corresponding catalytic groups in the antibody combining site. We report here that electrostatic interactions between a hapten and the complementary antibody can be exploited to generate catalytic amino-acid side chains in an antibody combining site. The antibody-catalysed reaction, a beta-elimination reaction, exhibits saturation kinetics, substrate specificity, competitive inhibition by hapten, and specific inactivation by a reagent that modifies carboxylate residues. PMID- 2922054 TI - Three amino acids of the oestrogen receptor are essential to its ability to distinguish an oestrogen from a glucocorticoid-responsive element. AB - Steroid hormone receptors activate specific gene transcription by binding as hormone-receptor complexes to DNA enhancer elements termed hormone responsive elements. A highly conserved 66-amino-acid region of the oestrogen and glucocorticoid receptors which corresponds to part of the receptor DNA-binding domain (region C) determines the specificity of target gene recognition. This region contains two subregions (CI and CII), encoded in two separate exons, that are analogous to the 'zinc fingers' of the transcription factor TFIIIA. The N terminal CI finger determines the recognition specificity of the hormone responsive element. A chimaeric oestrogen receptor, in which the CI finger is replaced with the corresponding glucocorticoid receptor CI finger region, activates transcription from a reporter gene containing a glucocorticoid responsive element, but not from a reporter gene containing an oestrogen responsive element. We report here that three amino acids located at the C terminal side of the oestrogen receptor CI finger play a key part in this specificity. PMID- 2922055 TI - Genomic footprinting with Taq polymerase. AB - The linear amplification of chemically sequenced DNA with DNA polymerase from Thermus aquaticus permits the direct detection of DNA methylation and protein-DNA interaction sites in vivo. PMID- 2922056 TI - More wicked ways with hormones. PMID- 2922057 TI - Soviet psychiatry. New independent association. PMID- 2922058 TI - Cortical physiology. Is grandmother an oscillation? PMID- 2922059 TI - Our ancestors. PMID- 2922060 TI - The Caenorhabditis elegans heterochronic gene lin-14 encodes a nuclear protein that forms a temporal developmental switch. AB - During wild-type development, a protein product of the Caenorhabditis elegans heterochronic gene lin-14 is localized to nuclei of specific somatic cells in embryos and early larvae, but is absent in late larvae and adult soma. Gain-of function lin-14 mutations cause the level of lin-14 protein to remain high throughout development, resulting in developmental reiterations of early cell lineages. The normal down-regulation of the lin-14 nuclear protein level encodes a temporal switch between early and late cell fates. PMID- 2922061 TI - Oscillatory responses in cat visual cortex exhibit inter-columnar synchronization which reflects global stimulus properties. AB - A fundamental step in visual pattern recognition is the establishment of relations between spatially separate features. Recently, we have shown that neurons in the cat visual cortex have oscillatory responses in the range 40-60 Hz (refs 1, 2) which occur in synchrony for cells in a functional column and are tightly correlated with a local oscillatory field potential. This led us to hypothesize that the synchronization of oscillatory responses of spatially distributed, feature selective cells might be a way to establish relations between features in different parts of the visual field. In support of this hypothesis, we demonstrate here that neurons in spatially separate columns can synchronize their oscillatory responses. The synchronization has, on average, no phase difference, depends on the spatial separation and the orientation preference of the cells and is influenced by global stimulus properties. PMID- 2922062 TI - A diacylglycerol analogue reduces neuronal calcium currents independently of protein kinase C activation. AB - Diacylglycerol analogues (for example 1,2-oleoylacetylglycerol, OAG) and phorbol esters are activators of protein kinase C, and have been widely used to study the function of this enzyme in both intact cells and cell-free preparations. Electrophysiological studies have shown that these activators can either depress or increase Ca2+ currents, or decrease K+ currents when applied outside the cell. It has been assumed that these effects are mediated by protein kinase C activation. Here we report that micromolar levels of OAG and phorbol esters depress Ca2+ currents in chick sensory neurons independently of their effect as activators of protein kinase C. The depression of the Ca2+ current is rapid and is unaffected by intracellular application of the protein kinase C inhibitors staurosporin, sphingosine and H-7. Furthermore, the activators were ineffective when applied intracellularly, indicating that their site of action is on the outside of the membrane. PMID- 2922063 TI - A dominant control region from the human beta-globin locus conferring integration site-independent gene expression. AB - The regulatory elements that determine the expression pattern of a number of eukaryotic genes expressed specifically in certain tissues have been defined and studied in detail. In general, however, the expression conferred by these elements on genes reintroduced into the genomes of cell lines and transgenic animals has turned out to be at a low level relative to that of endogenous genes, and influenced by the chromosomal site of insertion of the exogenous construct. We have previously shown that if regions flanking the human beta-globin locus are introduced into the mouse genome along with the human beta-globin gene, a level of expression comparable to that of endogenous genes can be achieved that is also independent of integration site. We have now defined a dominant control region with these properties consisting of 6.5 kilobases of DNA encompassing erythroid cell-specific DNase I hypersensitive sites. The identification of such dominant control regions could have important applications in somatic gene therapy. PMID- 2922064 TI - [The decision making process of the family physician in choosing a drug]. AB - The GP's decision-making process in selecting drugs, as determined empirically, is described. In most cases (approx. 90%), the GP depends on ready memory and chooses from among 4-5 drugs that come to mind first. The cognitive structure of the storage of drugs in the GP's memory is primarily determined by the chemical properties and action. Proprietary drugs constitute the nodes of this cognitive structure. Criteria involved beside those mentioned above are price, efficacy and Dutch make. Prescription preferences are primarily determined by side effects and efficacy, much less by price and product type (proprietary vs generic drugs). Analysis of the GP's decision-making process using general models of human decision making and consumer behaviour is a promising technique for further study of doctors' selection of drugs. PMID- 2922065 TI - [An infant with AIDS]. AB - A four-month-old girl was hospitalized with pneumococcal sepsis from which she recovered. Subsequently she developed various other infectious diseases, including chronic diarrhoea caused by Cryptosporidium. After a period with neurological symptoms, later sagittal sinus thrombosis and cerebral atrophy, she died at age 13 months. It was found that the child suffered from AIDS. The mother was seropositive and the virus had probably been transmitted via the placenta. Rapid recognition of infants and young children with AIDS is necessary, for in the near future more cases of this disease will occur. Antiviral treatment may bring about improvement in children as well. PMID- 2922066 TI - [Transient bone marrow inhibition caused by aminoglutethimide]. AB - A 53-year-old woman with reversible bone marrow insufficiency caused by aminoglutethimide (AGT) treatment of metastatic breast carcinoma is described. The clinical picture included moderate thrombocytopenia and severe granulocytopenia complicated by Gram-positive septicaemia and skin infections, and by oral candidiasis. Withdrawal of AGT and antibiotic therapy resulted in clinical and haematological recovery, but the patient died suddenly, probably from a cardiac cause. Autopsy revealed widespread bone metastases, but no bone marrow infiltration of breast carcinoma. The haematological hazards caused by application of AGT are discussed. PMID- 2922067 TI - [The surgical treatment of recurrent breast carcinoma of the axilla]. PMID- 2922068 TI - [Extrapyramidal movement disorders following the use of flunarizine]. PMID- 2922069 TI - [Is otitis media with effusion harmful for the language development of young children?]. PMID- 2922070 TI - [Unexplained fever with spontaneous remission in a patient who traveled in the tropics]. PMID- 2922071 TI - [Allergic reactions in the nasal mucosa]. PMID- 2922072 TI - [Neurotoxicity of lithium with normal lithium levels]. PMID- 2922073 TI - [Post-traumatic stress disorder: not only in war victims]. PMID- 2922074 TI - [Organic-psychiatric and psychoreactive disorders in AIDS]. PMID- 2922075 TI - [Clinically important drug interactions]. PMID- 2922076 TI - [Appropriate practice by specialists]. PMID- 2922077 TI - [Admissions and bed occupancy at the hospital before and after the beginning of budgeting; a dance of billions]. AB - Hospital budgeting was enacted in 1983 and led to a spectacular decrease of hospital admissions. Admissions of elderly patients were an exception, however; progress in medicine results in ever-increasing possibilities of adequate treatment for this group. The shortening of the average hospital stay, evident since a number of years, continued unchanged after 1982. Taking into account the greying of the patients, the number of hospital days per 100 of the population has decreased by 20% between 1982 and 1987. This descending curve grows increasingly steep. The evolution outlined has probably resulted in a 10-figure reduction. PMID- 2922078 TI - [Operations before and after the beginning of budgeting; ever better results from medical practice]. AB - The number of operations performed clinically has decreased fairly steeply, mostly since 1982, the start of hospital budgeting. This decrease concerns all age groups except that of 65 and older. It appears that especially the minor operations are performed in the outpatient clinic more often than formerly. In spite of the fact that this renders the clinical operation schedule gradually heavier, the mortality of patients undergoing clinical operations, already low, continues to decrease rather rather markedly. These findings strongly suggest that the progress of modern medicine also particularly benefits the aged. PMID- 2922079 TI - [An unusual expression of a complication following hysterectomy; the patient kneels in front of the doctor]. AB - During operation of a woman aged 54 years for inguinal hernias, abdominal hysterectomy was carried out as well. A severe wound infection occurred. Subsequently, the patient was unable to sit down because she could not flex the left upper leg. Laparotomy revealed thrombosis and sclerosis of the left ovarian vein which impaired contraction of the iliopsoas muscle. Adverse effects of hysterectomy are briefly discussed. PMID- 2922080 TI - [The use of collected body materials in epidemiologic research]. PMID- 2922081 TI - [Participation in sports during pregnancy]. PMID- 2922082 TI - [The effect of prevention of infections in travelers to (sub)tropical areas]. PMID- 2922083 TI - [The administration of calcium channel blockers in patients with cerebrovascular diseases]. PMID- 2922085 TI - [Legionella pneumophila infection in hotel Aktizeus in Heraklion on Crete?]. PMID- 2922084 TI - [Lasting neurologic injury in therapeutic lithium plasma levels]. PMID- 2922086 TI - [Syringomyelia from the neurosurgical viewpoint]. AB - Indications for, and methods of, surgical treatment in patients with syringomyelia are described. In 16 patients a syringomyelic cavity was drained. Clinical, radiological and operative findings and results are reported and discussed. In six of twelve patients followed up, progressive deterioration was arrested by operation and two patients improved. PMID- 2922087 TI - [Differential diagnosis of Friedreich ataxia]. AB - The clinical records of 72 patients with spinocerebellar ataxias which had manifested before the age of 20, were examined in a retrospective study. Depending on whether the muscle stretch reflexes in the legs were positive or negative, two groups were distinguished, that of early onset cerebellar ataxia with retained tendon reflexes (EOCA) (13 P.) and that of Friedreich's ataxia (FA) (59 P.). The clinical course was much worse in the FA patients compared with EOCA. Cardiomyopathy and diabetes mellitus were not a feature of EOCA. Scoliosis and a disturbed position sense in the toes were more frequent in FA cases. The striking differences in clinical signs and course of the diseases justify the differentiation of EOCA from FA, as suggested by Harding in 1981. PMID- 2922088 TI - [Space-occupying, traumatically-induced hemorrhage of the posterior cranial fossa]. AB - A total of 4,408 patients were treated for head injuries from 1980 to 1986 at the University Hospital of Innsbruck in Austria. Nine of them (0.2%) showed a traumatic, space-occupying hematoma in the posterior fossa. Clinical signs are often elusive, but tentorial or foraminal herniation with apnea may suddenly arise. Heightened awareness of these lesions and closely monitoring these patients are both necessary, especially when there is a fracture over the transverse sinus or the foramen magnum. Computed tomography helps to establish the diagnosis and leads to appropriate neurosurgical treatment. The overall mortality of patients with these lesions was 22% in our patients. PMID- 2922089 TI - [Evoked potentials before and following decompression craniotomy in space occupying cerebellar infarct]. PMID- 2922090 TI - [Paroxysmal kinesiogenic choreoathetosis]. PMID- 2922091 TI - [Intraosseous meningioma. A report of 2 cases]. PMID- 2922092 TI - [The morphology of the lumbar spinal canal]. AB - Measurements of cast preparations of epidural cavities yielded data characterising the "internal silhouette" of the lumbar vertebral canal. Three groups of different shapes of lumbar vertebral canal were found to be statistically distinguishable from each other. These are determined by the constitution of the patient. The different spatial capacity of the three types and the different relations of the diameters modify the value of the isolated determined distance, for example of the sagittal diameter at L5, which is a clinically extremely relevant factor that must be taken into account. PMID- 2922093 TI - [Safe placement of atrial shunt catheters using intracardiac ECG. Initial experiences with a new ECG adapter system in 33 patients]. AB - In 1960 Robinson inaugurated the method of placing atrial shunt catheters with the help of intracardiac ECG monitoring. Vulnerability to artifacts and problems with electrical safety (which have since been solved) led to its disuse. A newly developed ECG adapter proved free from artifacts and was practicable in 33 patients. 31 shunts were correctly placed without requiring time-consuming radiography. 2 extracardiac false positions were clearly identifiable by means of true negative results, which after correction showed a typical atrial ECG. The ECG method is compared with 9 other positioning methods. It seems to be superior to the conventional chest x-ray and equal to fluoroscopy. However, the method is not on a par with sophisticated measuring techniques such as intracardiac pressure monitoring or intravasal sonography. PMID- 2922094 TI - [Clinical aspects and diagnosis of lumbosacral perineural cysts]. AB - Perineurial cysts are sometimes space-occupying cystic dilatations of the lumbo sacral nerve roots at or distal to the junction of the posterior root and the dorsal ganglion. The wall is composed of perineurium and neural tissue. We report on 2 cases of upper sacral perineurial cysts with their computed tomography and myelography findings. Indication for operation is discussed: perineurial cysts should only be operated on if their clinical symptoms are clearly attributable to them and other causes like degeneration of the lumbar spine can be excluded. PMID- 2922095 TI - Idiopathic cervical arachnoid cyst. 3 case reports. AB - Three cases of cervical intradural arachnoid cysts of different forms are described in detail from the viewpoint of neuroradiological findings. In two patients the symptoms simulated juvenile muscle atrophy of unilateral upper extremity; the other case showed findings as in a tumour. It should be noted that in comparison with cysts at the thoracic level, cervical arachnoid cysts show various different neurological and neuroradiological findings. In this paper, some characteristics of cervical arachnoid cyst in myelography, CT and MRI are discussed, in addition to the neurological aspects. PMID- 2922096 TI - Sellar chondroma in a case of Ollier's disease. AB - Chondromas are rare intracranial tumours. Sometimes they occur as a manifestation of a 'generalised chondromatosis'. The authors present a case of sellar chondroma in a patient with Ollier's disease. The tumour showed a mainly suprasellar extension resulting in a chiasmatic syndrome. The pathogenesis of intracranial chondromas, their clinical features, and CT- and MRI-findings are discussed. PMID- 2922097 TI - [Etiology of the recurrence of lumbar intervertebral disk displacement]. AB - In a review for reasons of 100 disc prolapses reoperations we found in 62% a recurrence of disc prolapse at the same level, in 24% a recurrence at a different level, whereas in 14% we found that the nerve route was closely connected. We reoperated 44% in the first two years and 69% in the first five years. The time between the operations was prolonged if there was a short period of time for relief of pain after operation and a long period of preoperative symptoms. The variables of risk of a disk prolapse recurrence are recorded in a risk score, in which 64% of the patients belonged retrospectively to a risk group. The correlation between operation interval and score points showed that patients with short interval had high score ratings. PMID- 2922098 TI - New international headache classification. PMID- 2922099 TI - World-wide trends in multiple sclerosis mortality. AB - Mortality attributed to multiple sclerosis (MS) was analyzed for 35 countries around the world using World Health Organization reports from 1965 to 1984. Trends were plotted for the United States and Canada, for various regions of Europe, Israel, South America, Asia, Australia and some Pacific countries. In general, MS mortality has declined steadily in North America and most of western Europe as well as in countries with a western culture but has remained stable or increased in eastern and northern Europe. Although several Mediterranean countries reported a recent increased frequency of MS, it was not (yet?) evident in mortality data. Intensive prospective surveillance of MS frequency trends in selected regions of the world will determine the validity of the trends based on mortality. PMID- 2922100 TI - Secular trends in mortality rates from motor neuron disease in Kentucky 1964 1984. AB - All death certificates with amyotrophic lateral sclerosis (ALS) or motor neuron disease (MND) as the primary or underlying cause occurring among Kentucky residents between 1964 and 1984 were manually reviewed. Geographic variability within Kentucky was evident for three intervals, 1964-1967, 1968-1978, and 1979 1984, with a more marked pattern among females than among males. There was a shifting age pattern of MND mortality with a higher proportion of cases in older ages for the most recent time period. Again, this pattern was more marked among females. Furthermore, there was a slight increase in total average annual age adjusted ALS/MND mortality rates over the three intervals. The increase is slight, but with the previous stability of reported rates and the shifting geographic and age patterns, there is evidence to support the need for incidence studies targeted at specific environmental exposures. PMID- 2922101 TI - Epidemiology of motor neuron disease in two Italian provinces. Analysis of secular trend and geographic distribution. AB - Incidence and prevalence rates of motor neuron disease in two Italian provinces (Asti and Cuneo, Piedmont region) in the period 1971 through 1985 were estimated. The data were omogeneous in the investigated area, but an increasing incidence of the disease during the period studied was found, particularly in older age groups and in females. An increasing trend in mean age of onset of symptoms was also found. PMID- 2922102 TI - Transient ischemic attacks in the community: occurrence and clinical characteristics. A population survey in the area of Florence, Italy. AB - A simple self-administered questionnaire was mailed to a population sample of 8,626 (40-65 years old) to identify transient ischemic attacks (TIAs) that occurred in the previous 12 months. This study was conducted in a well-defined, medically controlled geographic area. 75.4% of the questionnaires were returned. The procedure identified 52 TIA cases (43 definite and 9 uncertain). The 12-month period prevalence for TIAs was 6.6 per 1,000 (95% confidence limits of 4.8-8.9) among the respondents. The annual incidence rate for first TIAs was 3.1 per 1,000 (95% confidence limits of 1.9-4.7). Our results differ from those reported in hospital series or in population surveys based on clinical records, with higher incidence and prevalence rates, female preponderance and higher frequency of vertebrobasilar attacks. PMID- 2922103 TI - Stroke in a French prospective population study. AB - Since 1985 there has been a Stroke Registry in Dijon to record every stroke occurring in the population of a city of 140,000 inhabitants. The survey has been exhaustive and included the numerous sources of information as well as CT scanning. The annual incidence is 145/100,000 with an annual specific incidence of 170/100,000 in men, 126/100,000 in women. The annual specific incidence shows a female preponderance until 30 years of age, after which the males lead from the age of 30 to 80, when the rates become equal. Sixty-eight percent of strokes produced by infarct, 12% by lacunae, 5% by subarachnoid hemorrhage and 15% by cerebral hemorrhage. Differences exist in this distribution, with the preponderance of young people in subarachnoid hemorrhage, and cerebral hemorrhage is commoner in the 5th decade while infarct increases with age in both sexes. Infarct appears commoner during winter, transient ischemic attacks during summer, while cerebral hemorrhage has a constant incidence during the year. Mortality is high mainly during the 1st month with 12.5% during the 1st week, 21.5% the 1st month and 30% the 1st year. Our results are in the mean similar to white occidental countries, but opposite to those observed in Japan; they emphasize the importance of the lacunar syndrome, and the seasonal variations in different types of stroke. PMID- 2922104 TI - Neurotensin in microdissected brain nuclei and in the pituitary of the lean and obese Zucker rats. AB - Neurotensin (NT) is a tridecapeptide common to the gastrointestinal tract and central nervous system which suppresses food intake when centrally injected in various regions of the hypothalamus. We measured neurotensin levels in several microdissected brain nuclei as well as in the pituitary in 10 obese hyperphagic Zucker (fa/fa) rats, 9 heterozygous Fa/fa and 5 Fa/Fa lean rats. The greatest NT concentration and content were observed in the anterior lobe of the pituitary in the median eminence and in the lateral preoptic area (500 to 1000 pg/area, 3 to 5 ng/mg protein). NT was also detected in the median preoptic area, paraventricular (PVN), supraoptic, ventromedian nuclei (VMN) (about 250 pg/nucleus, 1.5 to 2 ng/mg protein). The smallest amounts were found in the suprachiasmatic (SCH) and accumbens nucleus (about 100 pg/nucleus, 1 ng/mg protein) and the peptide was absent in the cortex. NT content in the obese rat was significantly lower in all brain nuclei examined except the accumbens nucleus. This was most evident in the three nuclei involved in the regulation of feeding behaviour: PVN (276 +/- 38 (Fa/Fa) vs 188 +/- 15 (fa/fa) pg/nucleus, P less than 0.05), VMN (226, +/- 21 (Fa/Fa) vs 75 +/- 22 (fa/fa) pg/nucleus, P less than 0.001), and SCH (98 +/- 14 (Fa/Fa) vs 52 +/- 11 (fa/fa) pg/nucleus, P less than 0.05). There was no difference in the pituitary lobes between lean and obese rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2922105 TI - Stimulation of cholinergic receptor mediated secretion from the bovine adrenal medulla by neuropeptide Y. AB - The bovine adrenal medulla has been shown to possess binding sites for neuropeptide Y (NPY) and to release NPY in response to nicotinic receptor stimulation. Therefore we chose to investigate the influence of this peptide on adrenomedullary secretion using the retrogradely perfused bovine adrenal gland. The secretion of enkephalin-like peptides, norepinephrine and epinephrine was monitored after nicotinic cholinergic receptor stimulation in the presence and absence of NPY. NPY, alone, had no effect on secretion from the adrenal gland but produced a dose dependent increase in the secretion of enkephalin-like peptides and catecholamines when the cholinergic agonist, 1,1 dimethyl-4 phenylpiperizinium iodide, was present. The increase was significant at 1 X 10( 8) M when compared to release in the absence of NPY. The stimulatory action of other cholinergic agonists (nicotine and acetylcholine) was likewise potentiated by the addition of the neuropeptide. Peptide YY and pancreatic polypeptide did not mimic the effect of NPY when examined at the same concentration. In contrast to the potentiation observed in the perfused adrenal gland, NPY (1 X 10(-8) M) inhibited the cholinergic mediated release of enkephalin-like peptides and catecholamines from cultured bovine chromaffin cells. These data suggest that NPY may have the capacity to augment cholinergic receptor mediated secretion from the bovine adrenal gland. PMID- 2922106 TI - Effects of VIP and helodermin on thyroid hormone secretion in the mouse. AB - The two peptides VIP (vasoactive intestinal peptide) and helodermin have both been shown to occur within the thyroid gland: VIP in intrathyroidal nerves and helodermin in the C-cells. Both peptides have previously been demonstrated to enhance the release of radioiodine from the prelabelled thyroid in vivo. Since a considerable amount of radioiodine released from the thyroid under these conditions may be non-hormonal, we reexamined the effects of VIP and helodermin on thyroid hormone secretion by the use of the specific technique of studying the release of radioiodine bound to specific T4 antiserum in mice. We thereby found that anti-T4-bound radioiodine in T3-pretreated animals increased after intravenous injection of VIP (1.5 nmol/animal) to 280 +/- 24% (P less than 0.001), and after intravenous injection of helodermin (1.5 nmol/-animal) to 186 +/- 26% (P less than 0.001) compared to 78 +/- 5% in controls. As a comparison, the corresponding figure after injection of TSH (70 microU/animal) was approximately 350% (P less than 0.001). In contrast, in animals not pretreated with T3, neither TSH, nor VIP helodermin significantly altered the plasma level of anti-T4-bound radioiodine. Also, VIP and helodermin did not change the plasma levels of free T4 in non-pretreated animals. In summary, the sensitive and specific technique of measuring the release of anti-T4-bound radioiodine in vivo after pretreatment with NA 125I and T3 detected a stimulation of the thyroid hormone secretion by VIP and helodermin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2922107 TI - Radioimmunoassay of cyclo(His-Pro) in unextracted human plasma: report of a normal range and definition of factors critical for successful assay. AB - A radioimmunoassay for cyclo(His-Pro) (CHP) in unextracted human plasma that can detect 40 pg has been developed. Elution profile of CHP-like immunoreactivity (CHP-LI) corresponded precisely to those of [3H] cyclo(His-Pro) by both high pressure liquid chromatography and Sephadex G-25 column chromatography. In addition plasma CHP-LI exhibited close immunoidentity with authentic CHP. Charcoal treatment of plasma containing [3H] cyclo(His-Pro) resulted in loss of both CHP-LI and [3H] cyclo(His-Pro) activity. Plasma frozen at draw and assayed at 0, 6 and 24 hours displayed no change in CHP-LI while an aliquot from the same sample maintained at 4 degrees C and assayed at the same time intervals showed a 50% rise (0 hrs-856 +/- 47 pg/ml; 24 hrs-1288 +/- 85 pg/ml) (+/- SE) over 24 hours. In addition, plasma drawn from 14 volunteers and immediately frozen until assay yielded a mean CHP value of 829 +/- 64 pg/ml (+/- SE) while that of 14 volunteers that was maintained at 25 degrees C for 90 minutes was significantly higher at 1085 +/- 34 pg/ml (+/- SE) (p less than 0.03). Taken together, these data suggest that CHP can be easily measured in a direct RIA of human plasma, however, failure to maintain the sample frozen from the time of draw until assay may yield spuriously elevated values. PMID- 2922108 TI - Cholecystokinin system in striatal-nigral neuronal networks: infusion of quinolinic acid into rat striatum. AB - Unilateral infusions of quinolinic acid (QUIN) into the rat striatum led to an increase in cholecystokinin octapeptide sulfate-like immunoreactivity (CCK8S-LI) in the striatum and substantia nigra 4 days later. These changes were suppressed by the injection of gamma-aminobutyric acid into substantia nigra 30 min before sacrifice. Intraperitoneal administration of haloperidol 40 min before sacrifice also suppressed the effect of QUIN on CCK. These results suggest that nigrostriatal dopaminergic neurons regulate CCK neurons via presynaptic sites in the striatum, and also that striatonigral GABAergic neurons interact with CCK neurons in the substantia nigra. PMID- 2922109 TI - Immunohistochemical localization of secretogranin II in the rat cerebellum. AB - Secretogranin II (chromogranin C) is a peptide related to chromogranin A and secretogranin I (chromogranin B) which is secreted by a regulated pathway from both neurons and endocrine cells. In the present study we have determined by light microscopic immunocytochemistry its distribution in the cerebellum and in adjacent brain stem regions. Secretogranin II was found to be widely distributed throughout the gray matter of these regions. Highly immunoreactive structures in the cerebellar cortex included the majority of climbing fibers, a large number of mossy fibers, sparse varicose fibers in the molecular layer and a subpopulation of neuronal perikarya in the granule cell layer. The location and shape of these neurons are very similar to those of a novel type of cerebellar neurons which has been recently described. A moderate level of immunoreactivity was observed on fibers travelling among Purkinje cells and parallel to the pial surface in the Purkinje cell layer. A variable, but in general low, degree of immunoreactivity was also detectable in the perikarya of Purkinje cells. In the deep cerebellar nuclei a loose network of secretogranin II-positive fibers was visible. Neurons of the nuclei, however, were non-immunoreactive. A dense network of highly immunoreactive fibers was found throughout the brain stem regions adjacent to the cerebellum. Our results indicate that secretogranin II has in the cerebellum and adjacent regions a distribution more widespread than that of known regulatory peptides and suggest that the peptide-mediated signaling in the cerebellum plays a role more important that has been acknowledged so far. PMID- 2922110 TI - Developmental and regeneration-associated regulation of the limbic system associated membrane protein in explant cultures of the rat brain. AB - In the present study we have examined the topographic and temporal patterns of expression of the limbic system associated membrane protein by light and electron microscopic immunocytochemistry in organotypic cultures of the rat brain. The regional, cellular and subcellular distribution of staining in young cultures was similar to that in the intact brain of corresponding age. Since the tissue in vitro is isolated both from afferents and targets, short-term protein expression appears to be regulated by factors intrinsic to the neuron. In culture, the protein was present on the surface of neurons which are physiologically interconnected, such as neurons belonging to the septohippocampal system (cholinergic neurons in the septum and pyramidal and granule cells in the hippocampus). It was also present on the surface of axons and growth cones during process outgrowth. Thus, the limbic system associated membrane protein is expressed in an appropriate spatial and temporal pattern for mediating interactions between growing axons and their targets. The expression of the protein in culture showed some important differences as compared to the intact brain. With increasing age, there was an increasing scattering and disappearance of immunoreactivity in cultures fixed with paraformaldehyde/glutaraldehyde. The decreased immunoreactivity in aged cultures does not appear to reflect decreased protein synthesis, because unfixed and acetone-fixed explants continued to show immunostaining. Furthermore, dot-blot assays showed similar amounts of immunoreactivity in culture as in the intact brain of corresponding age. Thus, the age-dependent decrease of immunoreactivity may reflect altered insertion of the protein into the membrane or a modification of the epitope recognized by the antibody. There was a rapid increase (within 1 hour) of immunostaining on the surface of sprouting processes following mechanical lesion of mature, unstained axons. The altered distribution after tissue injury could be a means of ensuring specificity of connectivity during nerve fiber regeneration. On the basis of the reported findings, we suggest that system-specific membrane proteins, including the limbic system associated membrane protein, may mediate the formation of specific connections in the brain. Furthermore, we suggest that the reinnervation processes taking place after central nervous system injury may exhibit a similar molecular basis to the development of neural pathways. PMID- 2922111 TI - Co-release of neuropeptide Y and noradrenaline from pig spleen in vivo: importance of subcellular storage, nerve impulse frequency and pattern, feedback regulation and resupply by axonal transport. AB - The importance of subcellular storage, nerve impulse rate and pattern, and feedback regulation, as well as resupply by axonal transport for the release of noradrenaline and neuropeptide Y-like immunoreactivity, was studied in the blood perfused pig spleen in vivo. Vasoconstrictor responses were recorded as perfusion pressure changes. Subcellular fractionation experiments using sucrose density gradients showed a bimodal distribution of noradrenaline (peak concentrations at 0.8 and 1.1 M sucrose) while only one main peak of neuropeptide Y was present (at 1.1 M sucrose). Overflow suggesting release of noradrenaline and neuropeptide Y like immunoreactivity could be detected after 10 s stimulation at 10 Hz. The ratio for the output of noradrenaline and neuropeptide Y upon continuous nerve stimulation in control animals decreased with frequency. After inhibition of noradrenaline reuptake by desipramine the vasoconstrictor response and noradrenaline output were enhanced while the corresponding overflow of neuropeptide Y was reduced by 50% at 0.5 Hz. Stimulation with the irregular or regular bursting patterns at high frequencies caused larger perfusion pressure increase and relative enhancement of neuropeptide Y output compared to noradrenaline than a continuous stimulation both before and after desipramine treatment. A similar fractional release per nerve impulse was calculated both for [3H]noradrenaline (5.6 +/- 1.0 x 10(-5) and neuropeptide Y (7.3 +/- 0.3 x 10(-5). After reserpine treatment combined with preganglionic denervation the vasoconstrictor responses were more long-lasting, neuropeptide Y release was enhanced while noradrenaline content and release were reduced by 99%. The difference in neuropeptide Y overflow between continuous and bursting types of stimulation was smaller after reserpine treatment. After prolonged intermittent stimulation with regular bursts (20 Hz) for 1 h the splenic content of neuropeptide Y was reduced by 58%, while no change was observed for noradrenaline. The maximal perfusion pressure increase upon prolonged nerve stimulation after reserpine was similar in control and reserpine-treated animals, but after reserpine the vasoconstrictor response and neuropeptide Y release were subjected to fatigue. Ligation experiments of the splenic nerves revealed the splenic neuropeptide Y content was resupplied by axonal transport with a calculated total tissue turnover time of 11 days. In contrast, axonal transport contributed only to a marginal extent for the resupply of noradrenaline.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2922112 TI - The onset of myogenesis in denervated mouse skeletal muscle regenerating after injury. AB - Denervation of skeletal muscle stimulates increased turnover of muscle nuclei and connective tissue cells. The present investigation tests whether denervation "primes" myogenic precursor cells, so that the onset of DNA synthesis in muscle precursors after traumatic injury occurs earlier than in innervated muscle. The left legs of 29 male BALBc mice were denervated, and 1 week later small incisions were made in the tibialis anterior muscles of both legs (denervated and innervated). At specific times after injury each mouse was injected once with tritiated thymidine to label replicating muscle precursors. Muscle lesions were sampled 10 days after injury (when all precursors had fused to form myotubes) and prepared for auto-radiography. The presence of labelled myotube nuclei showed that muscle precursors had been synthesizing DNA at the time when [3H]thymidine had been injected. Our data suggest that very few precursors were proliferating in denervated muscle within 30 h after injury, and the onset of myogenesis at 30 h was essentially the same in denervated and innervated muscle. The retrospective analysis indicates that there were also similar proportions of muscle precursors proliferating at different times after injury, in regenerating lesions of both denervated and innervated muscle. Thus, denervation does not stimulate an earlier regenerative response in injured skeletal muscle. PMID- 2922113 TI - American Academy of Neurology. 41st annual meeting program. Chicago, April 13-19, 1989. Abstracts. PMID- 2922114 TI - Building and promoting the executive team. PMID- 2922115 TI - Nursing and administration: a synthesis model. AB - The position taken in this article is that nursing administrative practice is a synthesis of knowledge and skills from the two major fields of study, nursing and administration. This synthesis is unique, needs further explication, and differs from a simple combination of content from two separate fields. Expanded study of nursing is an essential component of graduate programs in nursing administration and embraces both discipline and practice considerations. It proceeds from the perspective of clients as pluralities and organizations and systems as appropriate units of analysis. Nurses in executive positions, operating from an expanded knowledge base, have an opportunity to empower nursing and exert substantial influence on the nature and direction of health care. Concurrently they can empower other members of the executive team through development of creative patterns of interdependence as the organization pursues the goal of high quality, evenly distributed, cost-effective patient care. PMID- 2922116 TI - Nurse executive leadership: a corporate perspective. AB - It is a new age of understanding for nursing leaders. New corporate leadership positioning and power allow nurses the opportunity to evaluate leading abilities and to develop innovative leadership models. A corporate perspective sheds new light on old and difficult leadership problems. New sources of information are useful to all nursing leaders as they guide professional nurses, students, physicians, administrative colleagues, and others involved in health care delivery. PMID- 2922117 TI - Management preparation for nurse executives: the dual degree option. AB - Nurses have the clinical expertise that enables them to better understand the complex issues inherent in management of the delivery of health care. Yet without adequate preparation in management, as well as training of higher levels of nursing theory and research, nurses will be less prepared to compete at higher levels as the system continues to change. The University of Colorado offers a program designed to meet these needs, which serves as a national model for other schools of nursing considering such a curricular change. Further research needs to be conducted to identify the specific components of a graduate program that will enable the nurse executive to develop advanced nursing practice skills while developing the management skills necessary to achieve effectiveness in the practice setting. Because the long-term outcome of the dual degree model is still unknown, the effectiveness of the program in the health care system over time will be evaluated in relation to three outcomes: first, the effectiveness of program goals and objectives for producing successful nurse executives; second, the effectiveness of the curriculum design in preparing successful nurse executives; and third, satisfaction of graduates with the program and with their preparation. Participants in the dual degree program look forward to meeting this challenge. PMID- 2922118 TI - The nurse executive and interdisciplinary team building. AB - Team-building efforts of the nurse executive will raise nursing's status and strengthen nursing's image as a reliable, self-managed department able to make valuable contributions to health care delivery. Nurse administrators who assume the responsibility of building and maintaining productive interdisciplinary teams at the executive level will be rewarded with increased visibility, recognition, and power. Such opportunities for leadership should not be ignored or left to the purview of hospital administrators, physicians, or any other discipline. PMID- 2922119 TI - The theory of bureaucratic caring for nursing practice in the organizational culture. AB - Changes in the health care environment have raised many questions related to patient care. How are political, economic, legal, and technological caring decisions made? How is spiritual caring fostered? How can ethical caring be the grounds on which moral decisions are made? What new policies must be designed to enhance the human perspective in corporate policy, and how will these principles and policies guide actions? The impact of the Theory of Bureaucratic Caring on the corporate enterprise will necessitate a system shift from a narrow to a broad focus where management and caring views can exist side by side and realistically represent the transformation of health care organizations to benefit humankind. PMID- 2922120 TI - Executive teamwork at the University of Michigan Medical Center. PMID- 2922121 TI - Executive teamwork at the University of Michigan Medical Center. PMID- 2922122 TI - Creating the foundation for an effective executive team. PMID- 2922123 TI - The evolution of the nurse executive role from one perspective. PMID- 2922124 TI - Forming and executive team. PMID- 2922125 TI - Effective staff functioning in dealing with executive teams. PMID- 2922126 TI - Reflections of the executive team. PMID- 2922128 TI - The changing health care environment: challenges for the executive team. PMID- 2922129 TI - Factors associated with pregnancy-induced hypertension. AB - This article reports the results of a correlational study that explored the association between the three factors of pregravid weight, prenatal weight gain at 28 weeks and maternal age, and the subsequent development of pregnancy-induced hypertension (PIH). A significant relationship between low maternal age and PIH development was found. Further data analysis showed that PIH occurred significantly more often when the second trimester mean arterial pressure (MAP) did not drop to a level lower than the first trimester MAP. Clinically, emphasis should be placed on early detection of women at high risk for PIH development. Analysis of the MAP changes could prove to be a low-cost, effective and low-risk predictive test for PIH development. PMID- 2922127 TI - The corporate challenge. PMID- 2922130 TI - How each state stands on legislative issues affecting advanced nursing practice. PMID- 2922132 TI - Smoking and health: 25 years of progress. PMID- 2922131 TI - Sudden hearing loss. AB - The condition of "sudden hearing loss" is characterized by an abrupt and usually unilateral reduction of hearing. The loss may affect any frequency and may range from mild to profound in degree. This type of hearing loss causes particular difficulty in assessment because several chronic conditions may manifest similar initial symptoms. Sudden hearing loss is an emergency which demands astute recognition and a prompt otolaryngological referral. The key to prompt recognition in the primary care setting includes the maintenance of a high index of suspicion accompanied by a thorough and accurate patient history. PMID- 2922133 TI - The social epidemiology of smoking during pregnancy among Mexican women. AB - The association between maternal tobacco smoke exposure and hazards to reproduction has been investigated since the turn of the century. Numerous studies have demonstrated an increased risk to the developing fetus as a result of maternal smoking. This risk continues to manifest itself postnatally into childhood. The present study examined both risk factors for and consequences of smoking behavior among a sample of 50 pregnant women consecutively admitted to the obstetrics ward of the Tijuana General Hospital, Tijuana, Mexico. A questionnaire completed postpartum examined social, cultural, and economic variables for the mother, and physical variables of the newborn. Twenty-one subjects were smokers and 29 were nonsmokers. The number of previous pregnancies per subject was significantly higher in the group of smoking mothers. Overall, 86.2% of the nonsmoking mothers had three or fewer pregnancies versus 52.4% of the smoking mothers (p less than or equal to 0.005). It was also noted that the smoking subjects tended to be light smokers (90% reported smoking ten or fewer cigarettes a day, with an average of 4.27 years of smoking history). No difference in knowledge of the harmful effects of smoking during pregnancy was observed between the two groups; however, the proportion of subjects whose mothers and siblings also smoked was significantly higher (p less than or equal to 0.005 and p less than or equal to 0.01, respectively) in the smoking groups. The results are discussed in terms of antismoking prevention and health promotion programs for the developing world. PMID- 2922134 TI - Smoking in the workplace: research needs and potential applications. PMID- 2922135 TI - Nonsmoking/smoking policy implementation at the state level. PMID- 2922136 TI - The smoke-free hospital: a smoke-free worksite. PMID- 2922137 TI - Implementation of a smoking policy in the United States Army. PMID- 2922138 TI - Rainier Bancorporation's policy on smoking. PMID- 2922139 TI - Evaluating worksite smoking policies. Methodologic issues. AB - This paper discusses the methodologic issues one confronts when studying the impact of worksite smoking policies, using one such study as an example. Topics covered include defining the research questions, deciding on timing of measurements in relation to policy implementation, advantages and disadvantages of cohort versus cross-sectional research designs, and alternative measurement techniques. The sample study examined changes over one year in the smoking related behaviors and attitudes of employees of a hospital that initiated a restrictive smoking policy, in relation to employees of a comparable hospital without a restrictive policy. The short term impact on ambient carbon monoxide was also examined. A case is made for studying the impact of smoking policy in the context of other strategies for reducing smoking prevalence at the worksite, such as individual treatment and organizational initiatives to motivate smoking cessation. PMID- 2922140 TI - "Smokeless cigarette" faces legal challenge. PMID- 2922141 TI - Human abuse through the ages. PMID- 2922143 TI - The sexual abuse of boys. PMID- 2922142 TI - The need for physicians to recognize sexual abuse in children. PMID- 2922144 TI - Child abuse: where are we going? PMID- 2922145 TI - Perestroika, new mental health legislation, and Soviet psychiatry. PMID- 2922147 TI - Spouse abuse. PMID- 2922146 TI - Abuse of the child and anxiety in the adult. AB - We report on the early development and family background of 20 patients admitted to an anxiety disorders clinic serving a disadvantaged population. Sixteen of these 20 patients had been abused or neglected. Nineteen had a diagnosis of at least one personality disorder. We discuss the relationship between the patients' backgrounds and their current disorders. It is our thesis that the traumatic background of our patients is the major factor that allows anxiety to be passed across the generations. PMID- 2922148 TI - Torture and health care professionals. PMID- 2922149 TI - Fetal neglect and abuse. PMID- 2922150 TI - Child abuse: the physician's responsibility. PMID- 2922151 TI - Abuse of the adolescent. PMID- 2922153 TI - Confronting child abuse and neglect in New York State. PMID- 2922152 TI - Abuse of the elderly: misuses of power. PMID- 2922154 TI - Anorexia nervosa: the destructive pursuit of thinness. PMID- 2922155 TI - The physician's management of child maltreatment. PMID- 2922156 TI - Secondary syphilis in a prepubertal child. Differentiating condylomata lata from condylomata acuminata. PMID- 2922157 TI - AIDS among New York State children. PMID- 2922158 TI - Corrections please ... PMID- 2922159 TI - On the mark ... PMID- 2922160 TI - Off-tour nurse vs. primary nurse: defining the roles. PMID- 2922161 TI - Age discrimination. PMID- 2922162 TI - The role of the LPN or ... the problem of two levels. PMID- 2922163 TI - The new nursing organization. PMID- 2922164 TI - Managing the "super-achiever" nurse. PMID- 2922165 TI - Self-scheduling for professional nurses. PMID- 2922166 TI - Utilization review: a psychiatric perspective. PMID- 2922167 TI - Managing the borderline personality. PMID- 2922168 TI - Streamlined documentation through exceptional charting. PMID- 2922169 TI - Taking the "guesstimates" out of FTE budgeting. Full-time equivalency. PMID- 2922170 TI - The performance edge. PMID- 2922172 TI - Preoperative teaching: a need for change. PMID- 2922171 TI - A hospital-based learning center. PMID- 2922173 TI - Leadership: do it with style. PMID- 2922174 TI - Performance-based evaluations. PMID- 2922175 TI - Management rights in unionized hospitals. PMID- 2922176 TI - Decision-making and conscience: protecting values in a clinical area. PMID- 2922177 TI - Despite appearances, no clean bill of health for semiconductor trade. PMID- 2922178 TI - Changing benefits funding presents challenge for health professionals. PMID- 2922179 TI - Cancerphobia liability: will this be "tort of the decade" in the '90s? PMID- 2922180 TI - Replacing the 'soft' touch with the safe touch. PMID- 2922181 TI - Prescription VDT lenses alleviate visual discomfort of display users. PMID- 2922182 TI - Threshold shift in hearing level stems from non-occupational cause. PMID- 2922183 TI - Effective hearing programs require assessment, testing, enforcement. PMID- 2922184 TI - Judge refuses to quash AIDS suit. PMID- 2922185 TI - Cost reduction trend forces new practices in occupational medicine. PMID- 2922186 TI - Is the color of your skin dangerous to your health and safety at work? PMID- 2922187 TI - Surgical reconstruction of the arthritic knee II. PMID- 2922188 TI - Cementless total knee replacement in patients 50 years old and under. AB - In this article, the authors present their initial experience with a cementless total knee prosthesis implanted in a young, active group of patients. The results compare favorably to reported cemented series. PMID- 2922189 TI - New Jersey low contact stress knee replacement system. Ten-year evaluation of meniscal bearings. AB - A metal-backed, interchangeable, meniscal bearing knee replacement system has been designed to combine low constraint forces with low contact stresses (LCS) to allow nearly normal joint articulation and loading as well as long-term wear resistance of the implants. System components allow unicompartmental, bicompartmental, tricompartmental, and revision knee arthroplasties. In this prospective comparison study, the early series of cases used methyl methacrylate for prosthesis-to-bone fixation, whereas the more recent series of knee replacements used sintered-bead porous coating to allow tissue ingrowth stabilization of all implants. Overall results in the first 149 cemented cases with 2- to 10-year follow-up (mean 7.6 years) were good to excellent in 85.2 per cent, fair in 3.4 per cent, and poor in 11.4 per cent using a strict knee scoring scale. Fair and poor results were seen predominantly in multiply operated and implant revision cases. The best cemented results were noted in primary cases, 95.1 per cent of which had good to excellent results. Overall results in the first 208 cementless cases with 2- to 7-year follow-up (mean 4.4 years) were good to excellent in 91.8 per cent, fair in 2.4 per cent, and poor in 5.8 per cent. Fair and poor results were also seen predominantly in multiply operated and implant revision cases. The best cementless results were noted in primary cases, 98.2 per cent of which had good to excellent results. Of 140 meniscal bearing implants in the entire series, one dislocation occurred (0.7 per cent) which required open bearing replacement. Of 217 rotating platform bearing implants in the entire series, 7 dislocations occurred (3.2 per cent), which required open bearing replacement or revision of components for malposition. These dislocations were seen predominantly in revision cases involving insufficient flexion stability; 6 of the 7 cases were revisions. This study demonstrates the efficacy of mobile bearing elements for use in knee replacement arthroplasty. It is essential that flexion and extension gaps be controlled to maintain contact pressure on such bearings to avoid problems of subluxation or dislocation. PMID- 2922190 TI - High tibial osteotomy with fixation by a blade plate for medial compartment osteoarthritis of the knee. AB - Surgical techniques were described on tibial osteotomy above the tuberosity, the fragments of which were fixed with a Koshino blade plate. Postoperative clinical results on 176 knees with medial compartment osteoarthritis of 138 patients with an average age of 62.1 years were excellent in 110 and good in 55 knees with an average of 5.5 years' follow-up. The best knee score was obtained in the knee with postoperative limb alignment of 6 to 15 degree valgus angulation (standing). The results were satisfactory, especially in postoperative management, which was much easier with the Koshino blade plate fixation than with other methods. The sinking of the osteotomy site was checked through observation of screw movement in the slot of the plate during postoperative management in 53 selected knees, and the averaged distance of sinking was 3.9 +/- 2.5 mm. The time of mechanical bone union judged by cessation of sinking averaged 12.9 +/- 6.2 weeks after osteotomy. PMID- 2922191 TI - [Surgical treatment of critical valvular aortic stenosis in neonates and infants based on echocardiographic diagnosis]. AB - The results of surgical intervention are reported in 10 cases of critical valvular aorta stenosis diagnosed with echocardiography in neonatal age and infancy. The significance of echocardiography (2-dimensional, M-mode, Doppler) which does not mean stress for the patient in critical state and provides correct diagnosis is emphasized. Correct diagnosis contributes to the performance of operation in appropriate time as well as the use of immediately performable and correct surgical technique is considered necessary. These are the first cases in Hungary where open heart operations have been carried out on the basis of echocardiography in neonatal age and infancy. The good results proved the adequacy of the solution. PMID- 2922192 TI - [A simple method of cervical myelography by lumbar injection of Omnipaque]. AB - The authors report on the experiences with cervical myelography performed in 94 cases in the past years at their Institute. On the basis of the results a simple and reliable procedure easy to perform with the lumbar administration of Omnipaque contrast material in lying position is described and recommended. Examinations performed by cervical puncture are justified only according to the authors' opinion if their method fails to be successful. PMID- 2922193 TI - [A new method of heparin therapy: subcutaneous administration in thromboembolism]. PMID- 2922194 TI - [After the convention of physicians and artists]. PMID- 2922195 TI - [Report of the experiences of a nursing instructor--teaching on the ward]. PMID- 2922196 TI - [I lay there full of anxiety and wanted to die]. PMID- 2922197 TI - Misunderstanding possible in scope of work. PMID- 2922198 TI - A primer on MedisGroups. PMID- 2922199 TI - Disposal of office hazardous wastes. PMID- 2922201 TI - Amend retirement plans for 1986 law changes. Health Care Group. PMID- 2922200 TI - Families and physician impairment. PMID- 2922202 TI - Dosage strategy in treating schizophrenia. PMID- 2922203 TI - Dreams and madness. PMID- 2922204 TI - Body image among 22 persons with acquired and congenital severe mobility impairment. AB - Interviews concerning body image were conducted with 10 persons with tetraplegia due to traumatic spinal cord injury and 12 persons with cerebral palsy. They all needed a wheelchair and daily assistance from another person. Their satisfaction/dissatisfaction with their body in different situations was reported on a visual analogue scale. The body size as estimated on a Body Puzzle was compared with true measurements. The body mass index of the 22 persons was calculated. These results showed only slight differences between the groups of persons with acquired and congenital motor impairment and did not differ from the results in a reference group. Information was obtained about different experiences of the interviewed persons, e.g. those from the viewpoint of a wheelchair user, lack of body language and moving about in dreams. In general, the adjustments made to the problems concerning body image by the persons with severe mobility impairment were successful. This finding is important in the light of the efforts among persons with severe mobility impairment to reach equality and 'a normal life'. PMID- 2922205 TI - Preliminary evaluation of a pressure clinic in a new spinal injuries unit. AB - A pressure clinic is described, and its effectiveness in preventing pressure sores assessed. Preliminary results suggest that the incidence of pressure sores can easily be reduced by the introduction of this service. PMID- 2922206 TI - The natural history of neurological recovery in patients with traumatic tetraplegia. AB - During the years 1965 to 1986 the Rehabilitation Institute in Konstancin, Poland provided treatment for about 1400 patients admitted to hospital within the first hours or days after injury to the cervical spinal cord. This communication presents an analysis of 122 patients with tetraplegia, with absent sensation or only slight deep sensation preserved on admission. The patients showed considerable neurological recovery of the paralysed muscles. The analysis includes the age of patients, the level and degree of spinal cord injury, the mechanism of spinal injury, the time interval from injury to the return of sensation, voluntary movements and bladder automatism functions, as well as the ability to walk. PMID- 2922207 TI - Energy cost of paraplegic locomotion with the ORLAU ParaWalker. AB - Ten subjects with neurological lesion levels between T4 and T9 have been evaluated in the laboratory at ORLAU using their orthosis in its mechanical form alone (without FES assist). Initially the oxygen consumption at rest was measured. Then the patients were asked to walk (orthotic gait) at their preferred constant steady speed for a period of 5 minutes. Min. VO2 was measured during the exercise. From these readings the energy cost and consumption of the patients' gait was calculated. Our results show that the ParaWalker allows more efficient walking than do bilateral long leg braces and a paraplegic 3 point gait. It also shows that higher speeds with lower energy cost walking is possible with a different orthotic approach for high or mid thoracic lesion paraplegics. We believe that the energy demands to walk with the ParaWalker are within sustainable limits. PMID- 2922208 TI - Spinal cord degeneration associated with type II decompression sickness: case report. AB - The medical history, clinical and neuropathological findings at necropsy are described in a 50-year-old male amateur diver who suffered from Type II decompression sickness, a spinal 'bend'. He survived as a paraplegic for 4 years. In the spinal cord upward Wallerian degeneration in the posterior columns and downward degeneration in the corticospinal tracts was explained by multiple small and medium sized infarcts affecting the centripetal blood supply to the cord. There was preservation of a rim of subpial fibres on the surface of the posterior and lateral columns. The grey matter and nearby white matter (supplied by the centrifugal arterial supply) was unaffected. PMID- 2922209 TI - A case of post-traumatic syringomyelia. Neuropathological findings after 1 year of cystic drainage. AB - A 58-year-old man sustained C4-C5 post-traumatic myelopathy with C3-C4 subluxation, slight compression of C3 vertebral body, C4 spinous process fracture and C6 compression fracture. He subsequently developed syringomyelia from C4 to C6, which was shunted into the subarachnoid space. Postoperatively, there was some but insignificant improvement of his symptoms although a postoperative metrizamide spinal computerised tomography showed complete drainage of the cyst. This patient died 1 year later. Autopsy examination of the spinal cord showed extensive damage of the posterior half of the cord at C3-C4 but the damage was much less extensive from C4 to C6 (where the syrinx was located), affecting mainly the right dorsal column at C4 and the right dorsal column and right anterior horn at C5-C6. In this patient, the syrinx developed in the partially damaged segments of the cord at the level of the spinal fractures and complete drainage of the cyst was not followed by satisfactory relief of his symptoms. PMID- 2922210 TI - Urinary problems in decompression sickness. PMID- 2922211 TI - Even children have arthritis. AB - Children experience a number of problems related to juvenile rheumatoid arthritis (JRA), including pain, stiffness, and loss of mobility that interferes with normal growth and development. Innovative nursing in a variety of settings is needed to manage the child with this chronic illness. PMID- 2922212 TI - The effects of play therapy on developmental achievement levels of abused children. AB - Child abuse has been a visible social problem in America over the last several years, but a difficult one to study by social scientists. Play therapy can have a positive effect on the developmental achievement levels of these abused children. PMID- 2922213 TI - Developing a quality home care program for children. AB - Many children who might have died or been institutionalized before can now be cared for in the home by their families with an increase in home care and high technology services. Home health agencies must respond to this need by initiating and developing quality pediatric home care programs. PMID- 2922214 TI - Retention of infant CPR instruction by parents. AB - Twenty-one families of high-risk infants were followed at home after receiving cardiopulmonary resuscitation (CPR) instruction prior to hospital discharge. Parents retained large amounts of theoretical knowledge about CPR up to 2 months following instruction. Skills were less well retained, but retention was better than reported for other lay groups. PMID- 2922215 TI - Nursing update: hypophosphatemic rickets. AB - Hypophosphatemic rickets is a nonnutritional condition that requires lifelong care and treatment. The Roy Adaptation Model serves the nurse in assessing and planning care for children and their families according to four adaptive modes: physiologic, self-concept, role function, and interdependence. PMID- 2922216 TI - Pediatric management problems (aortic coarctation). PMID- 2922217 TI - Community service: an avenue for nursing power. AB - Directing volunteer nursing expertise and services can greatly benefit the community, the nursing profession, and the nurse. This article presents concepts of power from a nursing perspective and the benefits of directing nursing expertise into a community. PMID- 2922218 TI - Anabolic steroids. PMID- 2922219 TI - Pain in the nonverbal patient: advocating for the critically ill neonate. AB - Relief of suffering is a major goal of nursing care. Nurses caring for nonverbal patients must develop specialized skills needed to assess pain and communicate their assessments to other nurses, physicians, and parents. Through collaborative efforts, pain relief for these patients can be achieved. PMID- 2922220 TI - Fiscal planning--the capital budget. AB - A well-prepared and accurate capital budget is a key part in successfully managing a nursing unit. A well-prepared capital budget will provide a nursing unit with the appropriate equipment needed for patient care. PMID- 2922221 TI - Identifying signs that nurses interpret as indicating pain in newborns. AB - PURPOSE OF THE STUDY: The purpose is to explore the behavioral and physiological signs that nurses interpret as suggesting the possibility of pain in the newborn. METHODOLOGY: The data collection instrument used was a General Information and Pain Sensitivity Questionnaire asking nurses to identify those physiological and behavioral signs that suggest the possibility of pain in the newborn. It was distributed to 109 nurses who worked in units where newborns are hospitalized; this was in a 1,000-bed tertiary care, university-affiliated hospital in the Midwest. RESULTS: Eighty-one nurses responded (74%). Three signs were selected "always" with a high frequency: fussiness, crying, and grimacing. When the scores of "always" and "usually" were combined for these three items, the figures are 96%, 79%, and 79%, respectively for selection rate. CONCLUSIONS: The fact that only three signs were selected with confidence suggests the difficulty and tentative nature of nursing decisions regarding the assessment of pain in the newborn. PMID- 2922222 TI - The importance of supporting nursing colleagues on scope of practice issues. AB - Although scope of practice issues contained in state statutes are often perceived as "tedious" by nurses, these issues are nonetheless important. This article cites a recent court case that demonstrates the importance of supporting nursing colleagues on these issues. PMID- 2922223 TI - A quick guide for home use of inhalant medications. AB - The chronic and frequently recurring symptoms in an obstructive lung disease such as asthma often dictate a complex home treatment program for the child and family. In planning for discharge of an asthmatic child, the nurse assesses and evaluates a variety of treatment modalities. PMID- 2922224 TI - Value of systematic post mortem radiographic examinations of fetuses--400 cases. AB - A retrospective study of 400 cases of fetal deaths has been carried out to assess the value of systematic post mortem radiological examination. Apart from general diagnosis purpose, special attention was given to the assessment of bone age and mineralization. The results were correlated with the clinical, U.S., chromosomal and pathological data. Computerized analysis of our information show the following results: (1) The radiological examination was valuable for the final diagnosis in 13.5% of cases. (2) It brings additional information in 34.5% of cases. (3) It had no diagnostic value in 52%. Furthermore, several points deserve attention such as apparition of teeth (21 weeks), calcaneum (24 weeks). Major osteoporosis was always associated with a constitutional bone disease or an infectious process. An excessive length of the upper limbs (12) was seen in 11 cases of anencephaly. We suggest that a radiological examination should not be routinely performed, when the diagnosis is otherwise obvious, but should be considered in the presence of dwarfism, or other limb abnormalities and when the gestational age is uncertain. The films provide essential information especially for further genetic counselling. Systematic post mortem radiographic examinations are performed in all naturally aborted fetuses over 11 weeks of gestation in our institution. A retrospective study of the last 400 cases was designed in order to assess the value of this examination, with regard to overall diagnosis and assessment of bone maturation and mineralisation. PMID- 2922225 TI - The association of congenital neuroblastoma and congenital heart disease. Is there a common embryologic basis? AB - Several authors have reported an association between neuroblastoma and congenital heart disease; others contend that, unlike specific well-known associations between malignancy and congenital defects (Wilm's tumor and aniridia, leukemia and Down's syndrome), no real relationship exists. We present three cases of cyanotic congenital heart disease in which subclinical neuroblastoma was found. We speculate that abnormal neural crest cell migration and development may be a common link between cardiac malformations and congenital neuroblastoma. PMID- 2922226 TI - Cardiovascular malformations and the neural crest. PMID- 2922227 TI - Failure of development of the growing breast after radiation therapy. AB - Four cases are presented in which young girls received radiation therapy to treat childhood malignancies. Subsequently, one breast, which had been included in the radiation field in each case did not develop. This phenomenon has been seen after orthovoltage as well as supervoltage therapy, but is not mentioned in recent diagnostic imaging literature. PMID- 2922229 TI - Basilar impression and osteogenesis imperfecta in a three-year-old girl: CT and MRI. AB - A 3-year-old girl with osteogenesis imperfecta developed symptomatic basilar impression. Her neurological symptoms were treated by foramen magnum decompression and laminectomy. This is an unusually young patient to have this condition. PMID- 2922228 TI - Percutaneous translumbar inferior vena cava central line placement in a critically ill child. AB - In patients requiring long term central venous access, common venous access routes may become occluded. Surgical placement of central venous catheters may not always be possible or optimal. Percutaneous translumbar inferior vena cava central line placement offers an additional access route. The technique of translumbar inferior vena cava central venous access is described in a critically ill child. PMID- 2922230 TI - Ultrasound screening for congenital cardiac malformations in the fetus. Its importance for peri- and postnatal care. AB - Congenital cardiac malformations (CCM) are the commonest congenital anomalies. Using ultrasonography (US), the incidence of CCM in a selected group of fetuses and the impact of CCM on perinatal and postnatal care was evaluated. The indication for fetal echocardiography (F-ECHO) in 152 pregnancies was a positive family history in 61, fetal arrhythmias seen by routine obstetrical controls in 53, suspected CCM during obstetrical US in 9, growth retardation in 3 and contracted maternal factors in 6. Twenty pregnancies had no special indication. F ECHO was performed between the 18th and the 39th gestational week. Twenty-seven cardiac malformations were found (18%), 10 of which were important; 3 succumbed at birth, 2 after surgical intervention, 1 was aborted and 4 needed intensive care at birth. Of 53 cases with arrhythmias, 3 needed special care during pregnancy: Digitalis in a case of atrial flutter, sick leave and bedrest in 2 with supraventricular tachycardia, premature delivery in 1 case with complete AV block due to an intraventricular tumor. The extremely high incidence of CCM in this group proves the need for careful fetal evaluation to detect malformations. Nowadays F-ECHO can and should be performed as early as in the 18th gestational week, allowing either to interrupt a pregnancy or to plan delivery in a well equipped center which provides the necessary measures for these newborns. PMID- 2922231 TI - An outbreak of meningococcal disease in Auckland, New Zealand. AB - A large epidemic of disease caused by Group A sulfonamide-resistant Neisseria meningitidis has been occurring in Auckland, New Zealand, from June, 1985, and peaking in October, 1985 (spring), and June, 1986 (winter). By the end of 1986 an overall attack rate of 8.3 cases/100,000 total population per year had been calculated. The attack rate in children younger than 15 years was 30.4/100,000/year and the highest rate occurred in children younger than 5 years: all Auckland 68.8/100,000/year; South and Central Auckland 98.7/100,000/year. Seventy-nine percent of cases younger than 15 years of age occurred in 30% of the childhood population. The overall case-fatality ratio was 7% with the highest rate (22%) occurring in male children age 1 to 2 years. An outbreak in an industrialized country of an infectious disease usually seen in developing countries calls for investigation of living conditions and other sociodemographic factors in the population affected. Specific action in the form of a vaccination program particularly targeted to those at risk was planned and implemented before the winter of 1987. PMID- 2922232 TI - Serum cortisol responses in febrile children. AB - Adrenocortical stress response in children with a variety of febrile illnesses was prospectively evaluated in 76 patients presenting to a general pediatric clinic with temperature greater than 101 degrees F (38.3 degrees C). Serum cortisol concentrations at presentation and again after recovery from infection were determined. Overall mean magnitude change in cortisol concentrations was 3.6 fold. Cortisol response was unrelated to the height of temperature but significant differences depending on clinical diagnosis were identified. The largest response (5-fold) was observed in patients with pneumonia, bacterial meningitis and fever of undetermined etiology. Current recommendations to double or triple replacement hydrocortisone dosage during times of increased stress in children with adrenal insufficiency are adequate only for simple febrile illnesses such as upper respiratory infection and streptococcal pharyngitis but could be subtherapeutic for infections such as pneumonia, meningitis and fever of undetermined origin, which imply a greater systemic involvement. It is possible, but untested, that a 4- to 5-fold increase in dosage would be more appropriate in those conditions. PMID- 2922233 TI - Blood cultures in private pediatric practice: an eleven-year experience. AB - We describe an 11-year experience with bacteremia in a two-physician suburban private pediatric practice. Patients studied were ages 3 to 24 months with a body temperature of greater than or equal to 39.4 degrees C and nonfocal illness. During these 11 years, 23 such babies had bacteremia, 21 with Streptococcus pneumoniae. Three risk factors for bacteremia were identified: absolute neutrophil counts greater than or equal to 10,500/microliters; cool season (November to April), and Yale observation score greater than 10. The positive predictive values for bacteremia were 33, 41 and 57%, respectively, when (1) absolute neutrophil count was greater than or equal to 10,500, (2) absolute neutrophil count was greater than or equal to 10,500 and it was the cool season, and (3) all 3 risk factors existed. Of 158 babies at low risk for bacteremia by these criteria, none was treated and none developed serious complications of bacteremia. Eight of the 23 bacteremic infants received no expectant antibiotic therapy and 15 received presumptive amoxicillin treatment in dosages ranging from 20 to 174 mg/kg/day. Twelve bacteremic infants either were not treated or received dosages of 100 mg/kg/day or less; complications developed in 5 of the 12 (persistent bacteremia, 2; facial cellulitis, 3). The remaining 11 bacteremic babies received approximately 150 mg/kg/day (range, 136 to 174) and none had complications (P = 0.03 by Fisher's exact test). The costs of identifying and treating infants suspected of having possible occult bacteremia were examined. PMID- 2922234 TI - A concurrent epidemic of respiratory syncytial virus and echovirus 7 infections in an intensive care nursery. AB - We describe concurrent outbreaks of respiratory syncytial virus (RSV) and Echovirus 7 (Echo 7) infections in a neonatal intensive care unit, including infants who had dual infections. Seventy-three infants were identified as having RSV from January through June, 1984. During the same surveillance period Echo 7 was cultured from 20 infants, and 6 infants had concurrent RSV and Echo 7 and RSV were isolated, but not concurrently. This dual outbreak of RSV and Echo 7 infections persisted for months despite infection control measures. Control procedures were complicated by: (1) cases of RSV infection at less than 72 hours of age, which had not previously been reported and which led to the reintroduction of RSV into "clean" areas; (2) the lack of a rapid diagnostic test for enterovirus infection; (3) the number of infants who were asymptomatic with each infection; and (4) the logistical problems of handling a dual pathogen outbreak in a confined setting. These problems were compounded by the many risk factors associated with nosocomial infections found in neonatal intensive care settings such as prolonged hospitalizations, endotracheal or nasogastric tubes and contact with many ancillary care personnel. PMID- 2922235 TI - Fever, bacteriuria and concomitant disease in children with urinary tract infection. AB - A total of 124 children aged 0.2 to 6 years were enrolled in a study of first time febrile urinary tract infection. The patient population was stratified in groups according to the stringency of criteria for fever and bacteriuria and the presence of concomitant disease. The major group of 88 patients consisted of children with fever greater than or equal to 38.5 degrees C measured at the hospital within 24 hours of diagnosis, bacteriuria verified by suprapubic bladder aspiration or repeated cultures of voided urine, but without concomitant disease. These children were mainly infected with attaching Escherichia coli specific for galactose alpha (1----4) beta galactose containing receptors and had laboratory evidence of inflammation. Another group of 11 children were distinguished with strictly defined bacteriuria and concomitant disease. These children were infected with nonattaching bacteria and had lower concentrations of C-reactive protein in serum and lower microsedimentation rates than the major group. Five of these children had a reduction in renal concentrating capacity. The study emphasizes the heterogeneity among patients with fever and bacteriuria but does not rule out the possibility of renal involvement in any subgroup. PMID- 2922236 TI - Tinea nigra palmaris and plantaris: a black fungus producing black spots on the palms and soles. PMID- 2922237 TI - Cat-scratch disease associated with a vertebral osteolytic lesion. PMID- 2922238 TI - An outbreak of tuberculosis in a family day care home. PMID- 2922239 TI - Laryngeal coccidioidomycosis causing airway obstruction. PMID- 2922240 TI - Cerebellar infarction as a complication of pneumococcus meningitis. PMID- 2922241 TI - Giardiasis and breast-feeding in urban Africa. PMID- 2922242 TI - Diagnostic value of acoustic reflectometry in children with acute otitis media. PMID- 2922243 TI - Charts: the TORCH syndrome revisited. PMID- 2922244 TI - Vertical transmission of Citrobacter diversus from mother to infant. PMID- 2922245 TI - Trends in mortality in children hospitalized with meningococcal infections, 1957 to 1987. AB - We reviewed charts of 261 children seen at Children's Hospital of Wisconsin from 1957 to 1987 with culture-proven meningococcemia or meningococcal meningitis, and we analyzed trends in mortality and disease severity for that interval. Overall case fatality was 10%, ranging from 9% in the period 1957 to 1963, to 16% in the period 1980 to 1987 (P = 0.15). The percent of patients admitted with severe disease increased from 14% to 38% (P = 0.001). When stratified by disease severity, case-fatality rates did not change with time. We conclude that technologic advances of the past 30 years had no measurable impact on mortality from meningococcal infection in our hospital and that crude case-fatality rates can be misleading if disease severity is not considered. PMID- 2922246 TI - Nursing makes a difference. PMID- 2922248 TI - NLN testing: products and services for registered nursing programs 1989. PMID- 2922247 TI - Recovery from childbirth--does the "postpartum period" last only six weeks? PMID- 2922249 TI - [Basic behavior guidelines in airplane hijacking]. PMID- 2922250 TI - [EEG in general practice to demonstrate primary intracranial tumors. Field of applications and limitations]. AB - In Denmark, the annual death rate due to primary intracranial tumours is 320, an unsatisfactory result of treatment that stresses the need of earlier diagnosis. This entails investigation on a wide range of indications. In a population with a low prevalence of a given disease, but with a high prevalence symptom which might be due to the disease in question, is required a highly accurate diagnostic test. Is EEG sufficiently reliable? PMID- 2922251 TI - [Herpes zoster neuralgia--a persistent therapeutic problem]. AB - Most patients with acute herpes zoster (AHN) who are younger than 50 yrs recover spontaneously and need no more specific medication than NSAID-analgetics. However, older patients and those treated with immunosuppressive medication are at high risk of developing postherpetic neuralgy (PHN), and may need intensive treatment for severe pain. Unfortunately there is no specific method so far to prevent PHN. In the prevention of PHN some promising results have been gained with antiviral drugs, sympathetic blocks, corticosteroids, psychotropic and anticonvulsive drugs. The earlier any of these treatments is started in AHM, the better results. When PHN has developed, in most cases there is no effective treatment to be offered. In the Pain Clinic of Helsinki University Hospital antidepressive and neuroleptic drugs as well as transcutaneous neurostimulation have been used for PHN treatment. PMID- 2922252 TI - [Penicillin allergy]. AB - Patients are often labelled "allergic to penicillin" without adequate reason. Since penicillins are frequently the drugs of choice, this label should not be accepted lightly. The allergic reactions to penicillins are of immediate, accelerated, or delayed-type hypersensitivity. The most serious reactions are those of acute- and accelerated-type, which are both IgE mediated. Ideally, patients suspected of being allergic to penicillins should be tested in succession with RAST, skin testing, and per-oral provocation. Patients with serious infections and documented penicillin allergy should undergo desensitisation. Patients with penicillin allergy have a slightly increased risk of reactions to cephalosporins. PMID- 2922253 TI - [AIDS/HIV in the Third World]. PMID- 2922254 TI - [Children and AIDS]. AB - Children suffering from HIV-infection is a serious and increasing problem all over the world. The pediatric AIDS cases are usually transmitted through vertical transmission from a HIV-infected mother to the fetus during pregnancy, but it is not possible before the age of 15 months to decide with certainty whether the infant is infected or not. The risk of HIV-transmission from mother to fetus is about 50 per cent. The prognosis of the infected infants are very bad, the morbidity and mortality are high. In USA 60 per cent of the infants with congenit HIV-infection have died before the age of 2 years. The progress of HIV-infection in infants and children is characterized by bacterial infections with subsequent sepsis, neurological symptoms and regression of the psychomotor development. Most of the families are basically suffering from severe psychosocial problems eg drug abuse and at least one of the parents is HIV-infected. A family with a HIV antibodypositive child is a family suffering from crises, illness, lack of resources and social isolation, and is therefore in need of medical, psychological and social treatment and support. It is urgent to help these children and their families through interdisciplinary intervention to give the children an optimal quality of life. To obtain this it is necessary with interdisciplinary comprehensive programs and multidisciplinary collaboration in the community. And in these programs it is important to prioritate the primary prophylaxis in trying to reduce the number of infants born in risk of HIV infection. PMID- 2922255 TI - [Norwegian propositions for blood transfusion practices]. PMID- 2922256 TI - [Why don't our patients take their medicine? An example from asthma/allergy care]. PMID- 2922257 TI - [Child abuse and neglect]. AB - There is still room for improvement with regard to legal protection of children, the education of parents as to the task of parenthood, and coordination between different specialties in assisting families with children through crisis situations. The article reports Scandinavian investigations into child abuse and the preventive measures hitherto introduced. The Scandinavian seminars on child abuse and neglect have been important forums for the exchange of experience, both with regard to research and clinical practice. PMID- 2922258 TI - [Clinical significance of controlled trials: estimation of confidence intervals for therapeutic effects]. PMID- 2922259 TI - A structural analysis of P. polycephalum U1 RNA at the RNA and gene levels. Are there differentially expressed U1 RNA genes in P. polycephalum? U1 RNA evolution. AB - U1 RNAs were isolated from P. polycephalum microplasmodia nuclei and sequenced. A P. polycephalum gene coding for U1 RNA was also isolated. The coding region of this gene differs at 3 positions compared to the isolated U1 RNA species. Both isolated RNAs and the gene encoded RNA can be folded according to the secondary structure model previously proposed for U1 RNA. Putative regulatory elements very similar to those required for efficient transcription of U RNA genes from vertebrates, in particular, the -200 distal enhancer element, are present in the flanking regions of this gene. The presence of several U1 RNA genes in P. polycephalum was confirmed by Southern blot analysis of genomic DNA. In contrast to yeast S. cerevisiae U1 RNA, P. polycephalum U1 RNAs have a length similar to that of U1 RNAs from higher eukaryotes. Nevertheless, P. polycephalum U1 RNAs probably differ from these RNAs in the 5'-terminal segment supposed to base-pair with the 5'-end of introns. The results are discussed taking into account phylogenetic evolution and functional role of U1 RNA. PMID- 2922260 TI - Distamycins inhibit the binding of OTF-1 and NFE-1 transfactors to their conserved DNA elements. AB - We investigated the effects of the antiviral agent distamycin A and of a distamycin derivative (FCE 24517) which possesses antineoplastic activity on the binding of some regulatory proteins to DNA. Both compounds inhibited the binding to DNA of the ubiquitous octamer binding factor OTF 1 and of the erythroid specific GATAAG protein (NFE 1). This was shown using the electrophoretic mobility shift assay on a DNA fragment of human gamma-globin gene promoter (-156 to -201), on the same fragment with a point mutation (T to C mutation) known to have an increased affinity of binding for NFE 1, on a DNA fragment of human histone H2B promoter and on a DNA fragment of mouse alpha 1 globin promoter. The ability of distamycin or of FCE 24517 to inhibit the binding was specific for AT rich sequences since neither drug inhibited the binding of nuclear protein factors to the sequence CCACACCC of the human beta globin gene. Binding to DNA was investigated by evaluating the drugs' ability to protect selected sequences from DNase I digestion (DNase footprinting). Distamycins binding was highly preferential for DNA sequences containing stretches of AT. These studies indicate that chemicals which have a high degree of DNA sequence-specific binding can selectively inhibit the binding of regulatory proteins to DNA. These effects might be responsible for modification of the transcription of specific genes and might to some extent account for these drugs' antiviral and antineoplastic activities. This approach offers potential for the investigation of new such drugs. PMID- 2922261 TI - Human dopamine beta-hydroxylase gene: two mRNA types having different 3'-terminal regions are produced through alternative polyadenylation. AB - Two kinds of cDNA (types A and B) encoding human dopamine beta-hydroxylase (DBH) were isolated from a pheochromocytoma cDNA library. Type A (2.7 kb) and B (2.4 kb) encoded the same amino acid sequence and were different only in 3' untranslated region. Type A contained 3'-extension of 300 bp at the end of type B. Subsequently, we isolated human DBH gene and analyzed genomic DNA by Southern hybridization. Human DBH gene (approximately 23 kb) was composed of 12 exons and existed as a single gene on genome. Exon 12 encoded 3'-terminal region of 1,013 bp of type A, including the 300 bp sequence. These results indicate that alternative use of two polyadenylation sites from a single DBH gene generates different mRNA types. This conclusion was supported by Northern hybridization and S1 nuclease mapping experiments. The ratio of type A and B mRNAs in pheochromocytoma was roughly 1.0 to 0.2. We found possible transcription regulatory elements, TATA, CCAAT, CACCC, GC boxes, near the transcription initiation site of DBH gene. Sequences homologous to glucocorticoid and cyclic AMP response elements were also observed. PMID- 2922263 TI - Two novel human DNA tandem repeat families from the hypervariable DNA probe homologous to human apolipoprotein CII-gene intron and D. virilis satellite. PMID- 2922262 TI - A human placental cDNA clone that encodes nonhistone chromosomal protein HMG-1. AB - From a human placental lambda gt11 cDNA library, we have isolated a cDNA clone that encodes the entire 215-residue amino acid sequence of HMG-1. Analysis of an internal sequence similarity suggests that the DNA-binding domains of HMG-1 are separated by a rather long and flexible linker segment. Southern blotting of DNA digested with BamHI indicated a highly variable number of genes (or pseudogenes) for HMG-1 in different species. Characterization of HMG-1 mRNA expression by Northern blotting showed that three mRNA species of approximately 1.0, 1.4 and 2.4 kb were expressed in all mammalian organs and cell lines examined. These included several rat organs at different stages of development. Northern analysis also suggested the occurrence of HMG-1 mRNA in an invertebrate and a plant species. PMID- 2922264 TI - Nucleotide sequence of a tomato mitochondrial tRNA(Cvs) (GCA) gene. PMID- 2922265 TI - Nucleotide sequence of the Sesbania rostrata leghemoglobin (Srglb3) gene. PMID- 2922266 TI - Primary structure of the Chlorella vulgaris small subunit ribosomal RNA coding region. PMID- 2922267 TI - Nucleotide sequence of Chlamydomonas reinhardtii mitochondrial genes coding for tRNA(Gln) (UUG) and tRNA(Met) (CAU). PMID- 2922268 TI - Nucleotide sequence of the rat low density lipoprotein receptor cDNA. PMID- 2922269 TI - Nucleotide sequence of the streptokinase gene from a group-G Streptococcus. PMID- 2922270 TI - Nucleotide cDNA sequence coding for the PVXc coat protein. PMID- 2922271 TI - An improved method for directly sequencing PCR amplified material using dimethyl sulphoxide. PMID- 2922272 TI - Anomalous values of Mycoplasma genomes sizes determined by pulse-field gel electrophoresis. PMID- 2922273 TI - Studies on the role of tetrazole in the activation of phosphoramidites. AB - The mechanism of the tetrazole-activated coupling step in the synthesis of oligonucleotides via phosphoramidites is studied with the help of model reactions: Treatment of diethoxydiisopropylaminophosphane with two equivalents of tetrazole resulted in a diethoxy-tetrazolophosphane, whose (31P)-NMR shift of 126 ppm is identical with the signal observed during internucleotide bond formation. A series of different related diethoxy-phosphorous-acid derivatives were also synthesized; their (31P)-NMR signals between 123.9 and 130.8 ppm are additional evidence for the intermediacy of a tetrazolide species. Further NMR investigations with more basic azoles showed that tetrazole is also active as a proton donor. PMID- 2922274 TI - (dT-dC)n and (dG-dA)n tracts arrest single stranded DNA replication in vitro. AB - Previous in vivo studies have indicated that (dT-dC)n.(dG-dA)n tracts (referred to here as (TC)n.(GA)n), which are widely dispersed in vertebrate genomes, may serve as pause or arrest signals for DNA replication and amplification. To determine whether these repeat elements act as stop signals for DNA replication in vitro, single stranded DNAs including (TC)n or (GA)n tracts of various lengths, were prepared by cloning such tracts into phage M13 vectors, and were replicated with the Klenow fragment of the E. coli DNA polymerase I, or with the calf thymus DNA polymerase alpha, by extension of an M13 primer. Gel electrophoresis of the reaction products revealed that the replication was specifically arrested around the middle of both (TC)n and (GA)n tracts of n greater than or equal to 16. However, whereas in the (TC)n tracts the arrests were less prominent at pH = 8.0 than at pH = 6.5-7.5, and were completely eliminated at pH = 8.5, the arrests in the (GA)n tracts were stronger at the higher pH values. These results, and previous data, suggest that the arrests were caused by formation of unusual DNA structures, possibly triple helices between partially replicated (TC)n or (GA)n tracts, and unreplicated portions of these sequences. PMID- 2922275 TI - Alternating d(G-C)3 and d(C-G)3 hexanucleotides containing 7-deaza-2' deoxyguanosine or 8-aza-7-deaza-2'-deoxyguanosine in place of dG. AB - The synthesis of alternating hexamers (8-13) derived from d(C-G)3 or d(G-C)3 but containing c7z8Gd (2) or c7Gd (3) instead of dG is described employing phosphoramidite-chemistry. Apart from the isobutyryl group the dimethylaminomethylene residue was used for the nucleobase-protection of 3. The methyl- and the cyanoethyl-phosphoramidites of 3 (5a-c) were synthesized. They were employed together with those of c7G or c7z8Gd in automated oligonucleotide synthesis. Tm-values as well as thermodynamic data of the oligomers 9, 10, 12, and 13 indicated that duplexes were destabilized if c7Gd replaced dG, whereas c7z8Gd stabilized the duplex structure. In contrast to d(C-G)3 which underwent salt-dependent B-Z transition, CD-spectra of oligomers containing c7Gd or c7z8Gd in place of dG showed retained B-conformation. PMID- 2922276 TI - Effects of 5-fluorouracil/guanine wobble base pairs in Z-DNA: molecular and crystal structure of d(CGCGFG). AB - The chemotherapeutic agent 5-fluorouracil is a DNA base analogue which is known to incorporate into DNA in vivo. We have solved the structure of the oligonucleotide d(CGCGFG), where F is 5-fluorouracil (5FU). The DNA hexamer crystallizes in the Z-DNA conformation at two pH values with the 5FU forming a wobble base pair with guanine in both crystal forms. No evidence of the enol or ionized form of 5FU is found under either condition. The crystals diffracted X rays to a resolution of 1.5 A and their structures have been refined to R-factors of 20.0% and 17.2%, respectively, for the pH = 7.0 and pH = 9.0 forms. By comparing this structure to that of d(CGCGCG) and d(CGCGTG), we were able to demonstrate that the backbone conformation of d(CGCGFG) is similar to that of the archetypal Z-DNA. The two F-G wobble base pairs in the duplex are structurally similar to the T-G base pairs both with respect to the DNA helix itself and its interactions with solvent molecules. In both cases water molecules associated with the wobble base pairs bridge between the bases and stabilize the structure. The fluorine in the 5FU base is hydrophobic and is not hydrogen bonded to any solvent molecules. PMID- 2922277 TI - Role of the branch site/3'-splice site region in adenovirus-2 E1A pre-mRNA alternative splicing: evidence for 5'- and 3'-splice site co-operation. AB - The adenovirus E1A gene encodes five overlapping mRNAs which are processed by alternative RNA splicing from a common pre-mRNA. To characterize cis-acting sequence elements which are of importance for the alternative 5'-splice site selection deletion and substitution mutants within the intron that is common to all E1A mRNAs were constructed. Deletion of the wild-type E1A branch site/polypyrimidine tract resulted in activation of a functionally redundant sequence located within an A/T rich sequence just upstream of the normal E1A lariat branch site. Removal of both regulatory sequences abolished in vivo splicing completely and did not lead to activation of cryptic 3'-splice sites at other locations in the E1A pre-mRNA. Furthermore we show that the sequence around the E1A branch site/3'-splice site region may have a more direct effect on the efficiency by which the alternative E1A 5'-splice sites are selected. Replacing the E1A branch site/3'-splice site region with the corresponding sequence from the second intron of the rabbit beta-globin gene or the first intron of the major late transcription unit resulted in drastic changes in E1A 5'-splice site selection. For example, with the E1A/beta-globin hybrid gene the 9S mRNA became the most abundant E1A mRNA to accumulate. This contrasts with the wild-type E1A gene in which almost undetectable levels of 9S mRNA were produced in transient expression assays. Our results strongly suggest that a cooperative interaction between 5'- and 3'-splice sites on a pre-mRNA determines the outcome of alternative splicing. PMID- 2922278 TI - Liver cell specific gene transcription in vitro: the promoter elements HP1 and TATA box are necessary and sufficient to generate a liver-specific promoter. AB - The hepatocyte-specific promoter element HP1, which is present in several genes specifically expressed in the liver, is active in an in vitro transcription system. The liver-specificity is retained in the in vitro system, as the activity is found in extracts of rat liver or hepatoma cells but is absent in an L-cell extract. Mutational analysis identifies HP1 as a 13 bp element: Two point mutations abolish the function of HP1. This inactivation is correlated with a reduced binding affinity of the transcription factors recognizing HP1. Two other mutants, which reduce the activity of HP1, bind the transcription factors with an affinity identical to the wildtype sequence. This suggests that the binding of the transcription factors is not sufficient for activation of HP1 dependent transcription. The function of HP1 depends on the presence of a TATA box within a distance of some 70 bp. Various TATA sequences are functional and no stereospecific alignment between HP1 and the TATA box is required. PMID- 2922279 TI - A novel photoproduct of 2'-deoxyguanosine induced by acetone photosensitization: 8-(2,3,4-trihydroxybutyl)guanine. AB - Acetone photosensitisation of 2'-deoxyguanosine in deaerated aqueous solution gives 8-(2,3,4-trihydroxybutyl)guanine as a major photoproduct. Its structure and that of its tetraacetate have been determined primarily by high resolution 1H NMR and mass spectrometry; a di-isopropylidene derivative has also been prepared. Mechanistic aspects of this novel photochemical transformation are discussed, particularly in relation to the alkaline cleavage of acetone photosensitised DNA at the sites of guanine bases. PMID- 2922280 TI - Activation of interferon-regulated, dsRNA-dependent enzymes by human immunodeficiency virus-1 leader RNA. AB - Human immunodeficiency virus-1 (HIV-1) leader RNA, which contains double-stranded regions due to inverted repeats, was shown to activate the dsRNA-dependent enzymes associated with the interferon system. HIV-1 leader RNA produced in vitro using SP6 RNA polymerase was characterized using probes for antisense and sense strand RNA. The RNA preparation was free from significant levels of antisense RNA. HIV-1 leader RNA was shown to activate dsRNA-dependent protein kinase in a cell-free system from interferon-treated HeLa cells. Affinity resins, consisting of HIV-1 leader RNA covalently attached to cellulose, immobilized and activated dsRNA-dependent protein kinase and 2-5A-synthetase. HIV-1 leader RNA, therefore, may be a contributing factor in the mechanism by which interferon inhibits HIV replication. PMID- 2922281 TI - The purification of an erythroid protein which binds to enhancer and promoter elements of haemoglobin genes. AB - An erythroid nuclear protein (EF1), originally detected as a protein binding within the nuclease hypersensitive site upstream of the chicken beta H-globin gene, has been purified. This protein of 37,000-39,000 molecular weight binds to three sites within the hypersensitive region: one between the CCAAT and TATA boxes, the second (further upstream) next to a NF1 binding site, and the third adjacent to a regulatory element found in a number of beta-globin genes. The EF1 protein also binds to an erythroid-specific promoter element of the mouse alpha globin gene and to two sites within the chicken beta A-globin enhancer. These six EF1-binding sites are related by the consensus sequence A/TGATAA/GG/C. A minor protein of molecular weight 72,000 which co-purifies with EF1 also binds to the same sequences. PMID- 2922282 TI - Pulse-field linkage of the P3, G6pd and Cf-8 genes on the mouse X chromosome: demonstration of synteny at the physical level. AB - Utilising pulse-field gel electrophoresis physical linkage between three mouse X linked genes has been demonstrated. The three genes, P3, G6pd and Cf-8 all lie within 400 Kb of DNA. This physical linkage mirrors the situation on the human X chromosome, representing the first demonstration of mouse/human synteny at the physical level. A detailed physical map encompassing 1.6 Mbp of this region is presented. A number of the rare cutter restriction enzyme sites within this map are partially blocked on the inactive X chromosome, presumably due to the methylation of CpG rich islands. Pulsed field gel electrophoresis therefore provides a useful tool for the study of X-inactivation over large regions of the X chromosome. PMID- 2922283 TI - Remarkably AT-rich genomic DNA from the anaerobic fungus Neocallimastix. AB - The genomic DNA of an anaerobic rumen phycomycete of the genus Neocallimastix has been purified and characterized. The non-repetitive fraction of the DNA has a G.C content of only 13%. The ribosomal RNA genes are highly reiterated, making up about 30% of the total DNA, and are evident as a more G.C-rich satellite with a repeating unit of about 9.4 kilobases (Kb). A.T-rich regions of DNA are highly dispersed and possess some sequence complexity. Chemical analysis of the DNA constituents reveals no evidence of modified bases. The genome of this anaerobic fungus has the highest A.T content of any organism so far described. PMID- 2922284 TI - Chromosome 7 long arm deletion breakpoints in preleukemia: mapping by pulsed field gel electrophoresis. AB - Chromosome 7 long arm deletions (7q-) are recurring chromosome abnormalities in leukemic bone marrow cells. In four patients we have previously localized the breakpoints in band 7q22 between the erythropoietin (EPO) and plasminogen activator inhibitor type 1 (PLANH1) genes that map 3 cM apart. The pro alpha 2(I) collagen (COL1A2, in band 7q22) and T cell receptor beta chain genes (TCRB, in band 7q35) have been found undeleted in one patient with an interstitial deletion. Pulsed field gel electrophoresis was used to map the breakpoints more accurately in two patients with a 7q- chromosome. The results suggested that lymphocytes and granulocytes give identical restriction patterns with several enzyme-probe combinations, and that a breakpoint possibly was within 195 kb of EPO in one patient but not in another. The gene order cen-COL1A2-EPO-breakpoint tel was suggested but physical linkage between COL1A2 and EPO was not found. A new putative TCRB restriction fragment length polymorphism or inherited methylation site was detected. PMID- 2922285 TI - Orientation of the agarose gel matrix in pulsed electric fields. AB - The technique of transient electric birefringence was used to investigate the effect of pulsed electric fields on the orientation of the agarose gel matrix. Orientation of the gel was observed at all electric field strengths. Very slow, time-dependent effects were observed when pulses of 10-100 V/cm were applied to 1% gels for 0.5-2 seconds, indicating that domains of the matrix were being oriented by the electric field. The sign of the birefringence reversed when the direction of the applied electric field was reversed, indicating that the domains tend to orient in the perpendicular direction after field reversal. Theories of gel electrophoresis will need to incorporate the orientation of the matrix in order to provide a complete explanation of electrophoresis in agarose gels. PMID- 2922286 TI - Synthetic repeating sequence DNAs containing phosphorothioates: nuclease sensitivity and triplex formation. AB - More than twenty repeating sequence DNAs containing phosphorothioates were prepared from the appropriate dXTPs with DNA polymerase I. The Tms of the modified DNAs were all lower than the parent polymers. A phosphorothioate group 5' to a pyrimidine gave rise to a large decrease than 5' to a purine, e.g., poly(dA).poly(dT) = 50 degrees; poly(dsA).poly(dT) = 44 degrees; poly(dA).poly(dsT) = 33 degrees; and poly(dsA).poly(dsT) = 26 degrees. The presence of phosphorothioate groups had a dramatic effect on triplex formation; poly[d(TC)].poly[d(sGsA)] spontaneously dismutases to a triplex at pH 8 whereas triplex formation in poly[d(sTsC)].poly[d(GA)] was inhibited. Surprisingly poly(dsG).poly(dC) had a Tm which initially decreased with increasing ionic strength. Resistance to digestion with pancreatic DNAse I did not correlate with phosphorothioate content. Poly[d(AsT)], poly[d(TsC)].poly[d(sGA)] and poly[d(sTG)].poly[d(sCA)] were resistant whereas poly[d(sAT)] and poly[d(sTsTG)].poly[d(CsAsA)] were rapidly degraded. Thus phosphorothioate groups cause small conformational changes and may reveal new families of conformational polymorphisms. PMID- 2922287 TI - Protein-DNA conjugates produced by UV irradiation and their use as probes for hybridization. AB - Several proteins have been crosslinked to DNA by low dose uv irradiation. The principle of the method is based on an efficient and fast radiation induced reaction of amino acid residues with DNA at low pH. The method seems to be of general applicability for crosslinking proteins to DNA in a very simple one step procedure. Some of such DNA-protein conjugates have been used as probes for hybridization experiments. DNA-protein A probes were found to be most useful. PMID- 2922288 TI - AP-1/jun binding sites mediate serum inducibility of the human vimentin promoter. AB - The vimentin gene is inducible by serum in quiescent Balb/c 3T3 cells, but the molecular mechanism of this induction is unknown. The results presented here represent a first step towards the elucidation of the pathway of events leading from growth factor-receptor interaction to this induction. A series of Bal 31 deletions of the human vimentin promoter are used to show that a sequence residing at -700 is responsible for the serum, and also TPA inducibility of this gene. This sequence is able to confer serum inducibility upon uninducible constructs regardless of its position and orientation, indicating that it is this element alone which is required for this induction. The isolated sequence is a strong enhancer as well. Further deletions and the use of synthetic oligonucleotides demonstrate that a 24-mer containing two AP-1/jun binding sites confer both serum and TPA inducibility upon the human vimentin gene. Gel retardation analysis confirms that this sequence binds an AP-1 -like protein. PMID- 2922289 TI - Enhancer functions and in vitro protein binding of native and mutated interferon responsive sequences. AB - Mutants of the Interferon responsive sequence (IRS) of the mouse and human (2' 5') A synthetase (moE-IRS and hE-IRS) were tested for their Interferon (IFN) inducible enhancer functions and for protein binding in vitro. Two complexes R1 and R3, were formed specifically with the hE-IRS. R3 migrated much faster and was about ten times more abundant than R1. R1 and R3 are increased about 2-fold in IFN-treated HeLa extracts relatively to extracts from non-treated cells. R1 and R3 seem to involve the same DNA sequence in the probe since they react identically to competitors. Two proteins of 69 and 46 kDa form the IRS specific complexes as revealed by UV cross-linking. Identical DNA probes bearing either the hE-IRS or moE-IRS form complexes of different characteristics with nuclear proteins, suggesting that the two IRS variants are the targets of binding of different proteins or of different protein complexes. PMID- 2922290 TI - Amplified inverted duplications within and adjacent to heterologous selectable DNA. AB - Plasmids containing a dihydrofolate reductase (DHFR) expression unit were transfected into DHFR-deficient Chinese hamster ovary (CHO) cells. Methotrexate exposure was used to select cells with amplified DHFR sequences. Three cell lines were isolated containing amplified copies of transfected DNA that had integrated into the Chinese hamster genome. Plasmid DNA was found to co-amplify with flanking hamster sequences that were repetitive (2 cell lines) and unique (1 cell line). Fragments comprising the junctions of amplified plasmid and CHO DNA were found to exist as inverted duplications in all three cell lines. These observations provide evidence that inverted duplication occurred prior to DNA amplification, thus underscoring the importance of inverted duplication in the DNA amplification process. PMID- 2922291 TI - Isolation and in vitro expression of the ricin A-chain gene: effect of deletions on biological activity. AB - The gene encoding the ricin A-chain was isolated and subcloned into an in vitro expression vector downstream from the SP6 promotor. mRNA encoding the A-chain strongly inhibited the translational activity of reticulocyte lysates. The inhibition correlated with glycosylase activity on rRNA, and could be abolished by addition of antibodies specific for ricin. mRNA generated after linearization of the vector at unique restriction sites within the A-chain coding sequence did not inhibit, except after linearization with ScaI. Also mutants lacking the 28 N terminal amino acids of native A-chain strongly inhibited the lysates. However, in both cases no glycosylase activity could be observed. We also show that the lack of a stop codon in mRNA does not affect the level of expression as assayed here. PMID- 2922292 TI - Nucleotide sequence of the structural genes for the mitochondrial cys, lys, gln and leu-tRNAs from the yeast Kluyveromyces lactis K8. PMID- 2922293 TI - Sequence of a small ribosomal RNA gene from Plasmodium lophurae. PMID- 2922294 TI - A wheat cDNA clone which is homologous to the 17 kd heat-shock protein gene family of soybean. PMID- 2922295 TI - Nucleotide sequence of the potato leafroll virus coat protein gene. PMID- 2922296 TI - Nucleotide sequence of a Lactobacillus delbrueckii gene encoding a minor (UCG) tRNA(ser). PMID- 2922297 TI - Nucleotide sequence of cytochrome P-450 cholesterol side-chain cleavage cDNA isolated from porcine testis. PMID- 2922298 TI - Cloning and sequence of mouse erythroid delta-aminolevulinate dehydratase cDNA. PMID- 2922299 TI - DNA sequence of a genomic clone encoding an Arabidopsis acyl carrier protein (ACP). PMID- 2922300 TI - Nucleotide sequence of the cynomolgus monkey apolipoprotein E cDNA. PMID- 2922301 TI - Sequence of the chloroplast rps14 gene encoding the chloroplast ribosomal protein S14 from rice. PMID- 2922302 TI - New recombinant linear DNA-elements derived from Kluyveromyces lactis killer plasmids. PMID- 2922304 TI - Looking for liberation. PMID- 2922303 TI - No fixed abode. PMID- 2922305 TI - Against the grain. PMID- 2922306 TI - When sex isn't any fun. PMID- 2922307 TI - Models for intensive care. Small patient big challenge. PMID- 2922308 TI - Models in intensive care. Non-verbal communication. PMID- 2922309 TI - Primary nursing. Night rites. PMID- 2922310 TI - Shoulder pain in stroke patients. PMID- 2922311 TI - Setting up a GP smear recall scheme. PMID- 2922312 TI - Fluid intake and urinary tract infection. PMID- 2922313 TI - Making sense of temporary transvenous pacing. PMID- 2922314 TI - Why figures cannot lie. PMID- 2922315 TI - Management. The name game. PMID- 2922316 TI - Needle point. PMID- 2922317 TI - Self-inflicted injury. PMID- 2922318 TI - Quest: NT's educational supplement. PMID- 2922319 TI - Quest. Building a strong foundation. PMID- 2922321 TI - Quest. The missing link. PMID- 2922320 TI - Quest. A model marriage? PMID- 2922322 TI - Standing empty. PMID- 2922323 TI - Poverty and infant deaths. PMID- 2922324 TI - Back to postbasics. PMID- 2922325 TI - The select few. PMID- 2922327 TI - Trading places. PMID- 2922326 TI - Disability. Facing up to my epilepsy. PMID- 2922328 TI - Who decides? PMID- 2922329 TI - Primary nursing. One to one. PMID- 2922330 TI - Management. Only if the face fits? PMID- 2922331 TI - Systems of life. No. 167. Senior systems. 32. Locomotor system 3--joints. PMID- 2922332 TI - A dearth of knowledge. PMID- 2922334 TI - Mental Handicap Nursing. PMID- 2922333 TI - Acute intestinal obstruction. PMID- 2922335 TI - Mental Handicap Nursing. The revolution is over. PMID- 2922336 TI - Planning for the elderly. PMID- 2922337 TI - Community initiatives. Accidents will happen. PMID- 2922338 TI - Community initiatives. Community patch-work. PMID- 2922339 TI - Back to school. PMID- 2922340 TI - Waking up to postoperative pain. PMID- 2922341 TI - Uncharted territory. PMID- 2922342 TI - Tumour takes all. PMID- 2922343 TI - Taste changes in cancer patients. PMID- 2922344 TI - Autonomy and accountability. PMID- 2922345 TI - Progressing nicely. PMID- 2922346 TI - Diabetes. Teaching the teaching of self-care. PMID- 2922348 TI - Nursing interventions for addicted patients. PMID- 2922347 TI - Diabetes. Sweet success. Interview by Andrew Heenan. PMID- 2922349 TI - The role of the psychiatric nurse in a community substance abuse prevention program. AB - There is an increasing awareness of the need for prevention of substance abuse related problems. The psychiatric nurse is especially equipped to strengthen the bonds among citizens and parents, health agencies and schools, law enforcement and hospitals to assist the community in the design and implementation of its own prevention program. The nurse is able to facilitate the community's own vested interests in a manner congruent with its needs. The nature and scope of nursing practice have traditionally included responses to health-conducive behavior. The nurse emphasizes self-determination and choice in health matters; therefore, substance abuse prevention efforts are likely to be incorporated by the community. The nurse provides the knowledge of addiction and abuse and assists the community in its health enhancement by using addiction and nursing theory, interpersonal process, research competencies, and teaching skills. PMID- 2922351 TI - Rehabilitation. PMID- 2922350 TI - The role of the addictions nurse specialist in a general hospital setting. AB - The four major roles of the addictions nurse specialist were defined. Specific examples of role implementation were described for the roles of practitioner, consultant, educator, and researcher. It is evident that the roles of consultant and educator permeate the roles of practitioner and researcher in the practice setting. Role differentiation among addictions nurse specialists will continue as the role becomes more widely utilized. Critical to the success of the addictions nurse specialist are (1) organizational support, (2) clearly defined role expectations, and (3) mutually established short- and long-term goals for the position. PMID- 2922352 TI - Community liaison nursing. An expanded role for the rehabilitation nurse. AB - Throughout the United States nurses are increasingly becoming responsible for the evaluation process for entry into inpatient rehabilitation programs. Often called "Liaison Nurses," they interface between rehabilitation centers and the broader health care community. PMID- 2922353 TI - Halo-body jacket immobilization in rheumatoid arthritis patients with cervical myelopathy. AB - The rehabilitation nurse may care for patients with arthritis in a variety of settings. When the patient has advanced RA, the problem of cervical myelopathy may require surgical intervention and use of the halo-body jacket immobilization orthosis. Expert pre- and postoperative management requires a knowledge of surgical nursing as well as rehabilitation nursing, in the traditional sense, to prevent complications and promote optimum recovery. When dealing with people who have lived with RA for many years, the rehabilitation nurse must continue to assess the patient's knowledge of the disease and use of self-management strategies and community resources. PMID- 2922354 TI - Client and family learning in the rehabilitation setting. AB - Learning in the rehabilitation setting, whether it be inpatient or community based, is a vital part of the client and family's role as consumers of rehabilitation care. Educational programs foster client participation in selecting appropriate modes of learning activities as they relate to the recovery process and help the client and family make a smooth transition into community living. Varied modes of instruction may be used, including practice sessions, group learning activities, computerized programs, use of videos as well as printed resources. The role of the nurse as educator coupled with a broad range of teaching strategies provides the client and family effective tools to make ongoing changes related to their functional abilities. The role of the rehabilitation nurse as an educator is an evolving one. No longer is the nurse practicing in a rehabilitative setting, whether it be inpatient or community based, guaranteed what appeared to be unending time to conduct educational programs. Past constraints, shortened stays, the client assuming an earlier role as a self-care agent, the focus on wellness, disabled individuals mainstreaming into community life, greater family involvement in rehabilitation efforts, and increased use of paraprofessionals force the nurse to strengthen and clarify her role as educator. Nurses need to value their teaching role as an integral part of the team effort. Strategies include scheduling teaching time with clients and families, recording activities and outcomes, discussing educational issues with other disciplines, and designing and promoting an environment that is conducive to learning. PMID- 2922355 TI - Often-ness. PMID- 2922356 TI - Simulation of vancomycin peak and trough concentrations using five dosing methods in 37 patients. AB - Five methods of dosing vancomycin (Matzke, Moellering, Nielsen, Lake-Peterson, and manufacturer's) were simulated in 37 patients. Ten serum samples were obtained after a 1-hour intravenous infusion of 6.2-20 mg/kg total body weight. A preinfusion serum sample was obtained from patients not studied on the first dose. Initial estimates of pharmacokinetic values were made using nonlinear iterative least squares regression and serum concentration-time data. These data were fitted to a two-compartment, open-infusion model. Simulations of the peak and trough serum concentrations at steady state for each patient were determined by multiple-dose simulated pharmacokinetics and each patient's pharmacokinetic values using the regimen suggested by each of the five methods. Steady-state serum concentrations, predicted systemic clearance by each method (except Lake Peterson), and the daily dose for each patient recommended by each method were determined. All the methods underpredicted actual drug clearance, with the Nielsen method having the lowest prediction. The Matzke method recommended the largest dosage. Using each of the methods, only 3-16% of patients would have achieved recommended peak and trough serum concentrations. In the simulation model used, no method performed satisfactorily in attaining the desired vancomycin peak and trough concentrations. We suggest that the Lake-Peterson method could be used initially, provided that monitoring is also performed to adjust the dosage regimen further. PMID- 2922357 TI - Drug-induced toxicities associated with high-dose cytosine arabinoside infusions. AB - The frequency and significance of central nervous system (CNS), ocular, and dermatologic toxicities associated with high-dose cytosine arabinoside (HDARA-C) infusions was evaluated. Patients were selected from one of three Southeastern Cancer Study Group protocols using HDARA-C 2-3 g/m2 body surface area (BSA) and their medical records were reviewed to identify and document the frequency of the toxicities. Those exhibiting CNS toxicity were compared across age, sex, race, previous standard-dose ARA-C or HDARA-C therapy, and infusion rate for toxicity occurrence. Statistical analysis was performed using Fisher's exact test with p less than 0.05. Of the 53 patients evaluated, 37.7% exhibited CNS, 37.7% ocular, and 45.3% dermatologic toxicities. Of the risk factors evaluated, only increasing age and previous ARA-C therapy approached statistical significance. The CNS toxicities associated with HDARA-C are clinically significant since permanent damage may result. Ocular and dermatologic toxicities usually resolve without medical intervention when HDARA-C therapy is discontinued. Further study is necessary to determine appropriate prophylaxis for these toxicities. PMID- 2922358 TI - Effects of alprazolam on respiratory drive, anxiety, and dyspnea in chronic airflow obstruction: a case study. AB - Alprazolam, an anxiolytic benzodiazepine, has a pharmacologic profile similar to that of diazepam. An intermediate half-life of 10-12 hours and a comparatively brief duration of activity relative to other anxiolytic benzodiazepines justified evaluation of a 0.5-mg test dose in an anxious patient with chronic obstructive lung disease. Subjective indexes, breath-by-breath respiratory drive response to hypercapnia, and blood alprazolam concentrations were determined before and after dosing. Subjective testing included a visual analog dyspnea scale, the state anxiety inventory, and subjective feelings visual analog scales (represented by alertness, calmness, and level of contentment). After dosing, the patient was better able to tolerate the rebreathing study technique. Statistically significant improvements in dyspnea (t - 10.20; p 0.0005), anxiety (t - 45.85; p less than 0.0001), alertness (t - 13.04; p less than 0.0001), cententedness (t - 12.27; p less than 0.0001), and calmness (t - 8.05; p less than 0.0001) occurred after alprazolam administration. Drive to breathe, as determined by mouth occlusion pressure and minute ventilation, was not statistically different before and after dosing. No adverse effects were reported or observed. Further study is warranted. PMID- 2922359 TI - Humeral locking nail: a preliminary report. PMID- 2922360 TI - Intraoperative femoral fractures associated with cementless total hip arthroplasty. AB - Between 1982 and 1986, 56 femoral fractures associated with cementless total hip arthroplasty (THA) were evaluated and compared to a randomly selected cementless THA control group without fractures. Depending upon the femoral shaft location, these fractures were classified as Types I, II or III. There were 45 (80%) Type I, 9 (16%) Type II, and 2 (4%) Type III fractures. Patient evaluations were quantified using a modified d'Aubigne-Harris scoring system. Nonparametric statistical methodology was used for fracture and control group comparisons. Treatment protocols were divided into various modalities, depending upon fracture classification. Type I and Type II fractures have no long-term prognostic hazards associated with them (P greater than 0.1), while Type III fractures appear to have analogous clinical results (sample size was too small for statistical analysis). PMID- 2922361 TI - Slipped capital femoral epiphysis. Results of treatment with a single cannulated screw. AB - Thirty patients with 36 slipped capital femoral epiphysis underwent pinning with a single cannulated screw. All patients were pinned in situ, allowed immediate weight bearing as tolerated, discontinued crutches at 6 weeks, and had a minimum of 1 year follow up (average 21 months). One patient had avascular necrosis, one patient had bilateral chondrolysis, and two patients required repinning. PMID- 2922362 TI - Rotationplasty: an option for limb salvage in childhood osteosarcoma. PMID- 2922363 TI - High lumbar disk herniations. Case reports. PMID- 2922364 TI - Intraarticular entrapment of a displaced olecranon fracture. A case report. PMID- 2922365 TI - Adolescent tibia vara. AB - Adolescent tibia vara is less common and less well described when compared to infantile tibia vara. Yet, the two share a significant number of features related to their epidemiology and histology. The two diseases differ most in their radiographic appearance. It does not, however, necessarily follow that their etiologies cannot be similar. By its epidemiology and histology, adolescent tibia vara appears to be related to repetitive trauma in the form of abnormal force directed on the medial tibial growth plate due to obesity, the adolescent growth spurt, or residual, incompletely corrected physiologic varus. Such forces may give growth plate suppression by the Heuter Volkman principle similar to what is thought to occur in infantile tibia vara. In the infant, this results in typical radiologic findings related to an epiphyseal ossification center which is cartilagenous and moldable and results in progressive medial wedging. In the adolescent, however, this ossification center is bony and, therefore, will not deform under stress. The growth plate, however, still responds with decreased growth resulting in varus deformity. Thus, adolescent tibia vara, by definition not related to trauma or infection, may in fact reflect the same pathologic process at work as in infantile tibia vara. PMID- 2922366 TI - Answer please. Omovertebral bone. PMID- 2922367 TI - Radiologic case study. Eosinophilic granuloma of the spine causing neurologic deficit. PMID- 2922368 TI - Intracapsular hip fractures: case reports and discussion. AB - Two cases of intracapsular hip fracture illustrate some of the treatment options available for Garden Stage IV fractures. In Case 1, a prosthesis was chosen because of the patient's physiologic age and poor general health. In Case 2, a compression screw augmented with a single-pin fixation to prevent rotation was used. This patient, although only 3 years younger than the first patient, was in good health. Although there was some posterior comminution, an attempt at fixation, allowing time for bone healing, was appropriate. Arthroplasty may be needed in several years if bone healing fails. PMID- 2922369 TI - Benign osteoblastoma. AB - A case of benign osteoblastoma is presented with a description of the typical clinical, radiographic, and pathologic features associated with osteoblastoma. The recommended treatment is tumor excision with avoidance of radiation therapy. PMID- 2922370 TI - Scoliosis in syringomyelia. PMID- 2922371 TI - False-positive and false-negative cytogenetic findings on chorionic villus sampling. PMID- 2922372 TI - Chromosome 1 deletion associated with increased nuchal fold thickness in the second trimester. PMID- 2922373 TI - Detection of rubella virus in fetal and placental tissues and in the throats of neonates after serologically confirmed rubella in pregnancy. AB - From 35 therapeutic abortions performed because rubella had occurred at 2-19 weeks of pregnancy, 120 fetal organs, 12 specimens of mixed products of conception, and 15 placentae were tested for rubella virus. Virus was isolated from 10 out of 11 fetuses (91 per cent) from women infected at 2-8 weeks, from 5 out of 8 (63 per cent) infected at 9-10 weeks, and from 2 out of 16 (13 per cent) infected at 11-19 weeks. Hybridization tests for viral RNA on 39 fetal organs from eight cases revealed infection in four additional fetuses. Virus was isolated from only 3 out of 15 aborted placentae, but hybridization tests on six placentae revealed infection in three additional specimens. Hybridization was superior to virus isolation for detecting rubella infection in products of conception and is therefore potentially the better method for examining chorionic villus biopsies. Rubella virus was isolated from the throats of 4 out of 9 infants (44 per cent) infected during the first 12 weeks of gestation, but from none of 13 infected after 17 weeks. Infants in the latter group are unlikely to infect susceptible contacts. PMID- 2922374 TI - [The shock lung syndrome in agranulocytosis patients]. PMID- 2922375 TI - [Campylobacter pylori and gastritis. Association or induction?]. PMID- 2922376 TI - [4 histopathologic differentiation grades in breast cancer? Data on the recommendations of the UICC in 1987]. PMID- 2922377 TI - [Bronchiolitis obliterans with organized pneumonia. Case report and discussion of the disease picture]. PMID- 2922378 TI - [Arteriopathia calcificans infantum in an infant with mucoviscidosis]. PMID- 2922379 TI - [Intravascular bronchioloalveolar tumor following interstitial giant cell pneumonia]. PMID- 2922380 TI - [Immunohistochemical demonstration of HIV-p24 antigen in formalin fixed and paraffin embedded brain and spinal cord tissue]. PMID- 2922381 TI - [Morphologic change in Campylobacter pylori associated gastritis in and following successful antibacterial therapy]. PMID- 2922382 TI - [The so-called endothelial vacuoles of the placental vessels--physiology or disease?]. PMID- 2922384 TI - The academy in 2000. PMID- 2922383 TI - [Comment on a previous article]. PMID- 2922385 TI - United States and Canadian Academy of Pathology (United States-Canadian Division of the International Academy of Pathology) annual meeting. San Francisco, March 5 10, 1989. Abstracts. PMID- 2922386 TI - Society for Pediatric Pathology. Annual meeting. San Francisco, CA, March 4-6, 1989. Abstracts. PMID- 2922387 TI - An ultrastructural and immunohistochemical evaluation of cytodifferentiation in neuroblastic tumors. AB - Twenty-six cases of neurogenic tumors consisting of 2 ganglioneuromas (GN), 8 ganglioneuroblastomas (GNB), and 16 neuroblastomas (NB) were studied to evaluate their cytodifferentiation. Ultrastructurally, a moderate to large number of neuritic processes and high density neurosecretory granules (NSG) were found in all cases of GN and well-differentiated GNB, in two-thirds of poorly differentiated GNB, in about a half of rosette-fibrillary NB, and in no case of round-cell NB. All GN and GNB had tumor cells which were positive for both chromogranin and neurofilaments. Of the 16 cases of NB, 12 were positive for chromogranin, and 13 and 15 were positive for Mr 200,000 and 68,000 neurofilament polypeptides, respectively. However, both markers appeared mainly in tumor cells maturing toward neuroblasts. Electron microscopy was helpful for the diagnosis of undifferentiated NB in those cases immunohistochemically negative for chromogranin or neurofilaments. We conclude that ultrastructural and immunohistochemical examinations are useful for the morphologic assessment of the degree of maturation of neuroblastic tumors. PMID- 2922388 TI - Squamous carcinoma of the esophagus in patients with Barrett esophagus. AB - Adenocarcinoma of the esophagus is a well-known complication of Barrett esophagus, especially in white men. We present three cases of squamous carcinoma of the esophagus in Barrett patients. All three patients were white men. None had a history of symptomatic gastroesophageal reflux or of Barrett esophagus, but all had substantial usage of alcoholic beverages and tobacco. All three tumors were located in squamous-lined mucosa above the Barrett mucosa. Columnar epithelial dysplasia was present in the Barrett mucosa of two of our patients, and the third patient had a squamous carcinoma of the pharynx. Squamous carcinoma represented 2% of Barrett-associated esophageal carcinomas at our institution in 1980 through 1986. Five additional cases were found in the literature, and all were also in white men. This demographic predominance stood in striking contrast to the 26% prevalence of white patients among those with squamous carcinoma of the esophagus at our institution (P less than 0.0002) and to the 50% prevalence of white men among our patients with Barrett esophagus (P less than 0.02). Two of the literature cases also had substantial alcohol and tobacco usage and had synchronous adenocarcinoma arising in Barrett mucosa. Our findings of a strikingly high prevalence of white men and of multifocal neoplastic changes in the upper aerodigestive tract suggest a pathogenetic relationship between squamous carcinoma of the esophagus and Barrett esophagus, possibly due to alcoholic beverage and tobacco usage. Endoscopic surveillance of Barrett patients for early detection of adenocarcinoma has been recommended; contemporaneous evaluation of the squamous-lined esophagus by biopsy and cytopathology may be advisable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2922389 TI - Ultrastructural morphometry distinguishes Burkitt's-like lymphomas from neuroendocrine neoplasms: useful criteria applied to the evaluation of a poorly differentiated neuroendocrine neoplasm of the nasal cavity masquerading as Burkitt's-like lymphoma. AB - The present study describes the potential usefulness of ultrastructural morphometry in diagnosis. Ultrastructural morphometric criteria were applied to the evaluation of a poorly differentiated neuroendocrine neoplasm of the nasal cavity that was initially thought to be a Burkitt's-like lymphoma (BLL). Although the nasal lesion in question failed to stain with over 50 cell lineage-relevant antibodies, it did stain for vimentin (an intermediate filament protein) and Ki 67 (a nuclear antigen associated with cell proliferation). Routine electron microscopy revealed a primitive neoplasm with abundant cytoplasmic lipid droplets and sparse dense granules with no intercellular junctions. Treatment options, which included extensive facial surgery, prompted more study. Tissue processed for the uranaffin reaction revealed sparse uranaffin-positive granules indicating the presence of true neurosecretory granules. An ultrastructural morphometric analysis of the neoplastic nuclei of this patient placed the tumor outside the morphometric domains for BLLs (18 cases) and neuroblastomas (11 cases) and within the morphometric domain of neuroendocrine carcinomas (9 cases). A greater mean standard deviation (P less than 0.05) and mean coefficient of variation (P less than 0.02) of nuclear perimeter in the neuroendocrine (NE) group related to the BLL group indicated greater nuclear pleomorphism within the NE group as illustrated in bivariate graphic displays. The possible origin of the neoplasm within the nasal mucosa is discussed. PMID- 2922390 TI - Postembedding immunogold electron microscopy for S100, tubulin, and cytoskeletal proteins in an amelanotic malignant melanoma. AB - A postembedding Protein A-colloidal gold technique was used for the ultrastructural immunocytochemical investigation of S100, tubulin, and cytoskeletal proteins in a Lowicryl K4M-embedded melanoma with numerous microtubules. S100 protein was localized in the cytoplasm and the nuclei of tumor cells. Melanosomes were not labeled with S100. Perinuclear intermediate filaments and filaments in cytoplasmic processes reacted positively for vimentin. The straight, rod-shaped, parallel intracisternal microtubules failed to react with antisera to tubulin, S100, vimentin, cytokeratin, neurofilaments, desmin, glial fibrillary acidic protein, and immunoglobulin light chains. These results give an improved correlation between the ultrastructural and immunocytochemical characteristics of the tumor, confirm the melanocytic origin of it, and demonstrate the application and usefulness of the postembedding immunogold method in the investigation of the protein composition of subcellular structures. PMID- 2922391 TI - A histiocytoid (epithelioid) vascular tumor of the ovary: occurrence within a benign cystic teratoma. AB - This report describes the case of a 22-yr-old woman with benign cystic teratomas of both ovaries. One of the teratomas contained a histiocytoid (epithelioid) vascular tumor. The lesion was composed of closely arranged, variably canalized, nests and cords of vacuolated, histiocytoid endothelial cells. Nuclear morphology was relatively uniform, but four to six mitotic figures were found per ten high power fields. Stromal inflammatory cells were notably sparse. Intravascular growth was absent. The patient remained well 30 mo after surgery. The authors review the literature concerning vascular tumors of the ovary and comment on histiocytoid vascular lesions in general. PMID- 2922392 TI - Natural-abundance 13C NMR study of glycogen repletion in human liver and muscle. AB - Optimizing the surface-coil design and spectral-acquisition parameters has lead to the observation of the 13C NMR natural abundance glycogen signal in man at 2.1 T. Both the human muscle and hepatic glycogen signals can be detected definitively with a time resolution of approximately equal to 13 min. A 1H/13C concentric surface coil was used. The 1H outer coil was 11 cm in diameter; the 13C inner coil was 8 cm in diameter. The coils were tuned to 89.3 MHz and 22.4 MHz, respectively. The 1H coil was used for optimizing field homogeneity (shimming) the magnet and for single-frequency decoupling of the C1 glycogen signal. Total power deposition from both the transmitter pulse and the continuous wave decoupling did not exceed the Food and Drug Administration guideline of 8 W/kg of tissue. Experiments were done for which healthy subjects returned to the magnets at different times for 13C NMR measurement. The spectral difference between experiments was within the noise in the C1 glycogen region. Because of the spectral reproducibility and the signal sensitivity, hepatic glycogen repletion can be followed. Four hours postprandial, hepatic glycogen increases by 3.8 times from the basal fasted state. The hepatic glycogen data correspond directly to previous biopsy results and support the use of 13C NMR as a noninvasive probe of human metabolism. PMID- 2922393 TI - Isolation and sequence of cDNA encoding a cytochrome P-450 from an insecticide resistant strain of the house fly, Musca domestica. AB - A cDNA expression library from phenobarbital-treated house fly (Musca domestica) was screened with rabbit antisera directed against partially purified house fly cytochrome P-450. Two overlapping clones with insert lengths of 1.3 and 1.5 kilobases were isolated. The sequence of a 1629-base-pair (bp) cDNA was obtained, with an open reading frame (nucleotides 81-1610) encoding a P-450 protein of 509 residues (Mr = 58,738). The insect P-450 protein contains a hydrophobic NH2 terminus and a 22-residue cysteine-containing fragment near the COOH terminus that is known to bind the heme; both of these features have been found in the more than five dozen vertebrate P-450 proteins of which the sequences are presently known. Interestingly, the termination codon UAA may be contained in a putative polyadenylylation signal (AAUAAA) of the mRNA. This P-450 protein exhibits the most similarity (27% amino acid positional identity) with mammalian proteins of the P450III family but qualifies as a member of another family, which we propose to designate the P450VI gene family. This cDNA and deduced protein sequence should provide important information in the study of evolution of the P 450 gene superfamily, as well as provide an important probe for studying the regulation of insect P-450 and understanding the molecular genetics of insecticide resistance. PMID- 2922394 TI - Phosphorylation and glycosylation of the luteinizing hormone receptor. AB - Purified testicular and ovarian luteinizing hormone/human chorionic gonadotropin (hCG) receptors are phosphorylated at serine and threonine residues by the catalytic subunit of the cAMP-dependent protein kinase (protein kinase A). Occupancy of the receptors by hCG significantly increased the rate but not the extent of phosphorylation. However, prolonged preincubation of receptors with hCG reduced the subsequent rate of receptor phosphorylation. Identical phosphopeptide maps were obtained for the phosphorylated ovarian and testicular receptors. The phosphorylated receptor, like the native receptor, bound to wheat germ lectin and hCG-Sepharose and migrated as a single band of Mr 90,000 (testis) and Mr 85,000 (ovary) on NaDodSO4/PAGE. Neuraminidase treatment of receptors caused reductions of molecular weight to 82,000 (testis) and 77,000 (ovary), and further treatment with O-Glycanase had minimal effect on molecular size. However, deglycosylation with N-Glycosidase and endoglycosidase F produced a single labeled polypeptide of Mr 59,000 for both gonadal receptors. Treatment of native receptors with neuraminidase caused no apparent change in binding of gonadotropin to blotted receptors, whereas deglycosylated receptors showed a major reduction in hormone binding. These results indicate that luteinizing hormone/hCG receptors are sialoglycoproteins with predominantly N-linked glycosyl residues that account for the size difference between testicular and ovarian receptors and that may participate in the interaction with gonadotropin. Receptor occupancy by agonist leads to a conformational change that facilitates its phosphorylation during initial binding and reduces the rate of phosphorylation after more prolonged exposure to hCG. PMID- 2922395 TI - Simultaneous recordings of force and sliding movement between a myosin-coated glass microneedle and actin cables in vitro. AB - To elucidate the molecular mechanism of muscle contraction resulting from the ATP dependent actin-myosin interaction, we constructed an assay system with which both the force and the movement produced by the actin-myosin interaction in vitro can be simultaneously recorded and analyzed. The assay system consisted of the giant internodal cells of an alga, Nitellopsis obtusa, which contain well organized arrays of actin filaments (actin cables) running along the cell long axis, and a glass microneedle (tip diameter, approximately 7 microns; elastic coefficient, approximately 40 pN/microns), which was coated with skeletal muscle myosin at the tip and extended from a micromanipulator at right angles with the actin cables. When the myosin-coated tip of the microneedle was brought into contact with the exposed surface of the actin cables, it exhibited ATP-dependent movement along the actin cables over a distance of 20-150 microns in 20-200 s (20 23 degrees C) and eventually stopped due to a balance between forces generated by the actin-myosin interaction (800-6000 pN) and by the bent microneedle. Since the load on the force-generating myosin molecules increased with the bending displacement of the microneedle (auxotonic condition), the relation between the load and the sliding velocity of the myosin heads past the actin cables was determined from the time course of the microneedle movement recorded with a video system. The shape of the force-velocity curve thus obtained was convex upwards, similar to that of the force-velocity curve of intact frog muscle fibers obtained under the auxotonic condition. PMID- 2922396 TI - Destabilization of an alpha-helix-bundle protein by helix dipoles. AB - The finite difference Poisson-Boltzmann method is used to calculate the electrostatic work of assembling the four alpha-helices of Themiste dyscritum hemerythrin to form the protein's observed antiparallel helical bundle. The calculations account for the interaction of each helix dipole with the high dielectric solvent as well as for pairwise interactions of the dipoles with each other. We find that the electrostatic work of assembly is dominated by unfavorable changes in dipole-solvent interactions rather than by favorable interactions between antiparallel helices. Furthermore, the electrostatic energy difference between the observed arrangement of helices in hemerythrin and at least one other possible helical arrangement is less than 1 kT. These results suggest that the helix dipole actually destabilizes the helical bundle and that it plays little or no role in producing the observed bundle geometry. PMID- 2922397 TI - A 4-kDa maize chloroplast polypeptide associated with the cytochrome b6-f complex: subunit 5, encoded by the chloroplast petE gene. AB - Four polypeptides, three of which are chloroplast-encoded, have been shown to be associated with the thylakoid membrane cytochrome b6-f complex. In this report, the gene for a fifth polypeptide, which copurifies with the b6-f complex, is identified through the use of an antibody generated against a synthetic decapeptide predicted from a maize chloroplast DNA sequence. The deduced 37-amino acid sequence of the immunoreactive 4-kDa polypeptide is 100% and 86% conserved in the respective similar open reading frames encoded by Nicotiana tabacum and Marchantia chloroplast DNA. The 4-kDa polypeptide is present in both etioplasts and chloroplasts of maize and is found as well in spinach, tobacco, pea, wheat, and rice thylakoids. Similar to the other subunits of the b6-f complex, it is intrinsic to the membrane, and its hydrophilic COOH terminus is located at the stromal thylakoid surface. We propose to call the 4-kDa polypeptide "subunit 5" and the chloroplast gene that encodes it the petE gene. PMID- 2922398 TI - Positive and negative regulatory elements in the mouse albumin enhancer. AB - Most enhancer elements so far described are comprised of multiple DNA binding sites for proteins that act to increase the rate of transcription. In this report we show that the far upstream mouse albumin enhancer element (-10.5 to -8.5 kilobase pairs) is a composite of at least three functional regions: a negative region that suppresses an otherwise positive, liver-specific enhancer element and a third region that by itself is inactive but in conjunction with the remaining elements overrides the effect of the negative region. The protein that binds to the overriding element is C/EBP, a liver-enriched transcription factor, whereas the newly identified protein that is responsible for full liver-specific enhancer activity is found in HeLa cell and spleen extracts as well as in extracts prepared from the liver. This latter protein may therefore be an example of a widely distributed protein that because of cell-specific modification or interaction has a tissue-specific, positive action on transcription. PMID- 2922399 TI - Transforming growth factor alpha may be a physiological regulator of liver regeneration by means of an autocrine mechanism. AB - We investigated whether transforming growth factor alpha (TGF-alpha) is involved in hepatocyte growth responses both in vivo and in culture. During liver regeneration after partial hepatectomy in rats, TGF-alpha mRNA increased; it reached a maximum (approximately 9-fold higher than normal) at the peak of DNA synthesis. The message and the peptide were localized in hepatocytes and found in higher amounts in hepatocytes obtained from regenerating liver. TGF-alpha caused a 13-fold elevation of DNA synthesis in hepatocytes in primary culture and was slightly more effective than epidermal growth factor. TGF-beta blocked TGF-alpha stimulation when added either simultaneously with TGF-alpha or a day later. TGF alpha message increased in hepatocytes stimulated to undergo DNA synthesis by TGF alpha or epidermal growth factor, and the peptide was detected in the culture medium by RIA. In the regenerating liver, the increase in TGF-alpha mRNA during the first day after partial hepatectomy coincided with an increase in epidermal growth factor/TGF-alpha receptor mRNA and a decrease (already reported) in the number of these receptors. We conclude that TGF-alpha may function as a physiological inducer of hepatocyte DNA synthesis during liver regeneration by means of an autocrine mechanism and that its stimulatory effects in this growth process are balanced by the inhibitory action of TGF-beta 1. PMID- 2922400 TI - Oxidative capacity of muscle and mitochondria: correlation of physiological, biochemical, and morphometric characteristics. AB - The oxidative capacity of cat skeletal muscles (soleus, gracilis, and gracilis chronically stimulated for 28 days) was derived from the total mitochondrial content in the muscle, the surface area of mitochondrial inner membranes, and respiratory activities of isolated mitochondria. Mitochondrial content was estimated by standard morphometry. The surface area of mitochondrial inner membranes per unit volume of mitochondria was estimated by a stereological method. The respiratory activities of isolated mitochondria were measured biochemically, using pyruvate/malate, glutamate/malate, succinate, or cytochrome c as substrate. Structurally and functionally, mitochondria from the three muscle types showed nearly identical characteristics. Oxidative activity was dependent on substrate; with succinate, 5.8 ml of O2 per min per ml of mitochondria was the rate most likely to represent physiological conditions. Oxidative activities of 3.1 ml.min-1.ml-1 with pyruvate/malate and 14.5 ml.min-1.ml-1 with cytochrome c as substrates were theoretical lower and upper bounds. The oxidative capacity of each of the three muscles was thus in direct proportion to the total volume of mitochondria in the muscle. The respiratory capacity of isolated mitochondria was very near to the maximal oxygen uptake rate of mitochondria that is commonly estimated in intact muscles of a wide variety of animals. PMID- 2922401 TI - Generation of human monoclonal antibodies to human immunodeficiency virus. AB - Based on the finding that cells producing antibodies to human immunodeficiency virus (HIV) circulate in the peripheral blood of HIV-infected individuals, attempts were made to immortalize such B cells with Epstein-Barr virus. Mononuclear cells from 58 HIV-seropositive subjects at various stages of HIV infection were transformed, and anti-HIV cell lines were derived from 4 subjects, all of whom were in early stages of infection. Seven of these cell lines have been stable with respect to antibody production for up to 15 months. Three lines are producing IgG antibody to the 41-kDa HIV transmembrane glycoprotein gp41 and 4 produce IgG antibodies to the 24-kDa HIV core protein p24, its precursors and a breakdown product. The antibodies are reactive by ELISA, by radioimmunoprecipitation, and by Western blot, demonstrating the feasibility of producing multiple stable cell lines synthesizing human monoclonal antibodies to HIV by immortalization of peripheral blood cells with Epstein-Barr virus. PMID- 2922402 TI - Ischemic and reperfusion injury of rat peripheral nerve. AB - A rat model of severe nerve ischemia was used to study the effects of ischemia and reperfusion on nerve conduction, blood flow, and the integrity of the blood nerve barrier. Conduction failure was consistently found in the sciatic-tibial nerve during 1- and 3-hr ischemic periods. Recovery of the compound muscle action potential was prompt and complete upon reperfusion following 1 hr of ischemia. However, after 3 hr of ischemia, recovery in the proximal portion of the sciatic nerve was less than 10%, and conduction block occurred in the distal portion of the nerve. Nerve blood flow was restored to only 55% and 45% of resting values following 1 and 3 hr, respectively, of ischemia and did not recover even after 2 hr of reperfusion. The blood-nerve barrier was not statistically impaired to the passage of [14C]sucrose following 1 hr of ischemia but was significantly impaired after 3 hr of ischemia. The permeability-surface area product was consistently greater following 1 hr of reperfusion than during the immediate reperfusion period. These data indicate that severe ischemia of peripheral nerve results in reperfusion injury, conduction block, and blood-nerve barrier disruption. Microvascular events, which may occur during reperfusion, may be important in amplifying the nerve fiber damage that began during ischemia. PMID- 2922403 TI - Anticancer activities of adenine nucleotides in mice are mediated through expansion of erythrocyte ATP pools. AB - ATP and AMP exhibit significant anticancer activities against established footpad CT26 colon adenocarcinoma in CB6F1 mice. Adenosine, inorganic phosphate, and inorganic pyrophosphate were without such effects under identical conditions. Daily intraperitoneal injections of adenine nucleotides in large volumes of saline, starting after the tumors became palpable, resulted in inhibition of tumor growth and a few "cures." The treatment was not toxic to the host as determined by changes in body weights. Weight loss observed in animals upon progression of the fast-growing CT26 tumors was slowed markedly in adenine nucleotide-treated mice. The inhibition of weight loss in tumor-bearing mice was shown to be neither the cause nor the effect of the inhibition of tumor growth. Intraperitoneal injections of AMP or ATP but not of adenosine yielded expansions of erythrocyte ATP pools in host animals. The expanded erythrocyte ATP pools are stable over a period of hours, while slowly releasing micromolar amounts of ATP into the blood plasma compartment, leading to several-fold increases in plasma (extracellular) ATP levels. Based on previous studies in which 1-5 microM extracellular ATP effectively inhibited the growth of a variety of tumor cells in several in vitro systems, it is suggested that similar levels of ATP in blood plasma account for the anticancer activities observed in a murine host. PMID- 2922404 TI - Energy metabolism of monocytic Ehrlichia. AB - We investigated if the monocytic Ehrlichia are totally dependent on their host cells for energy, or, as Rickettsia, are capable of some ATP synthesis in vitro. The Miyayama strain of Ehrlichia sennetsu and the Maryland and Illinois strains of Ehrlichia risticii were cultivated in a mouse macrophage cell line, separated from host cell constituents by procedures that included Renografin or Percoll gradient centrifugation, and tested after cryopreservation. Cells incubated without a metabolizing substrate contained little, if any, ATP. When the Ehrlichia cells were incubated for 1 hr at 34 degrees C with glutamine, significant amounts of ATP were detected. The amounts of ATP attained with glutamine were decreased in some instances by the addition of atractyloside, an inhibitor of adenine nucleotide translocase in mitochondria, and were decreased consistently and to a greater extent by 2,4-dinitrophenol. When ATP, instead of glutamine, was added to the ehrlichiae, upon incubation the amount of ATP was markedly decreased. Comparable responses under all these conditions were obtained with Rickettsia typhi, although the final ATP levels were higher. Control preparations derived from uninfected mouse macrophages or from the discards of the Ehrlichia purification procedures contained negligible amounts of ATP, which were not increased by incubation with glutamine. We conclude that with respect to ATP metabolism, the monocytic Ehrlichia resemble Rickettsia more closely than Chlamydia, even though Ehrlichia resemble Chlamydia in their intracellular location in the phagosomes and in possibly having a developmental cycle. PMID- 2922405 TI - Spatially and temporally resolved calcium concentration changes in oscillating neurons of crab stomatogastric ganglion. AB - Calcium concentration changes during oscillations of the membrane potential of crab (Cancer irroratus or Cancer borealis) stomatogastric neurons were monitored at many positions by using the calcium indicator dye arsenazo III and a photodiode array. Data analysis algorithms using signal averaging techniques were developed to improve the time resolution of the measured calcium changes. As previously reported, calcium oscillations were detected from all regions of the neuropil but not from the soma or axon. In some cells step increases in intracellular neuropil calcium were correlated with each of the action potentials in the burst (on the peak of the voltage oscillation). In other cells we observed calcium oscillations phase-locked to the membrane potential with no spike-related component. A few cells had both spike-evoked and graded potential components to the calcium oscillations. In those cells, the spatial distribution of the spike correlated calcium influx differed from that of the voltage-oscillation correlated calcium influx, suggesting that different neurites might interact with their postsynaptic targets with different mixtures of graded and spike-correlated transmitter release. PMID- 2922406 TI - The basal ganglia, the deep prepyriform cortex, and seizure spread: bicuculline is anticonvulsant in the rat striatum. AB - The gamma-aminobutyric acid antagonist, bicuculline methiodide (BMI), induces myoclonic seizures in rats when injected into the deep prepyriform cortex at concentrations lower than those that induce convulsions from the amygdala, hippocampus, or neocortex. This observation prompted the suggestion that the deep prepyriform cortex was responsible for seizure generation regardless of the neurotransmitter and neuronal circuits involved. Bilateral intrastriatal application of BMI protects rats against seizures induced by (i) local application of BMI into the deep prepyriform cortex and (ii) systemic application of bicuculline, pilocarpine (a cholinergic agonist), or kainic acid (a glutamate receptor agonist). The region of the striatum sensitive to the previously unknown anticonvulsant action of BMI is located in the immediate vicinity of the deep prepyriform cortex and is 100-150 times more sensitive to the anticonvulsant action relative to the sensitivity of the deep prepyriform cortex to the convulsant action of BMI. These data suggest a powerful gamma-aminobutyric acid dependent gating role of the basal ganglia in determining the seizure threshold in the forebrain. This argues against the suggestion that the deep prepyriform cortex plays a crucial role in the generation of seizures following systemic administration of convulsants. The discovery of an anticonvulsant action of BMI in the rat striatum contradicts the gamma-aminobutyric acid theory of epilepsy, which implies that deficits in the gamma-aminobutyric acid-mediated inhibition in the central nervous system lead to the emergence of seizures. PMID- 2922407 TI - Stimulus-specific neuronal oscillations in orientation columns of cat visual cortex. AB - In areas 17 and 18 of the cat visual cortex the firing probability of neurons, in response to the presentation of optimally aligned light bars within their receptive field, oscillates with a peak frequency near 40 Hz. The neuronal firing pattern is tightly correlated with the phase and amplitude of an oscillatory local field potential recorded through the same electrode. The amplitude of the local field-potential oscillations are maximal in response to stimuli that match the orientation and direction preference of the local cluster of neurons. Single and multiunit recordings from the dorsal lateral geniculate nucleus of the thalamus showed no evidence of oscillations of the neuronal firing probability in the range of 20-70 Hz. The results demonstrate that local neuronal populations in the visual cortex engage in stimulus-specific synchronous oscillations resulting from an intracortical mechanism. The oscillatory responses may provide a general mechanism by which activity patterns in spatially separate regions of the cortex are temporally coordinated. PMID- 2922408 TI - A stretch-activated K+ channel sensitive to cell volume. AB - The role of K+ channels in cell osmoregulation was investigated by using the patch-clamp technique. In cell-attached patches from Necturus proximal tubule, the short-open-time K+ channel at the basolateral membrane could be stretch activated by pipette suction, where a negative pressure of 6 cm H2O (588.6 Pa) was sufficient to increase the open probability of the channel by a factor of 4.0 +/- 0.8 (n = 7 tubules). A 50% reduction in bath osmolarity increased cell volume by 66 +/- 10% and increased the K+-channel open probability by a factor of 5.8 +/ 1.4 (n = 7) in the same cell-attached patches that were activated by pipette suction. A kinetic analysis indicates one open state and at least two closed states for this epithelial K+ channel. Both suction and swelling shorten the longest time constant of the closed-time distribution by a factor of 3, without significant effect on either the mean open time or the shorter closed-state time constant. The similar effect of suction and swelling is consistent with the hypothesis that stretch-activated K+ channels mediate the increase in macroscopic K+ conductance that occurs during osmoregulation of amphibian proximal tubules. Calculations based on a simple model indicate that small increments in cell volume could produce statistically significant increases in K+-channel activity. PMID- 2922409 TI - Calcium metabolism, serum thyroid-stimulating hormone, prolactin, and growth hormone in spontaneously hypercholesterolemic rats. AB - We have shown previously that spontaneously hypercholesterolemic (SHC) rats exhibit abnormal bone metabolism with advanced bone resorption, which develops with age. In this study, we measured serum levels of growth hormone, thyroid stimulating hormone, and prolactin in addition to several parameters of calcium metabolism and renal function in young (6-week) and old (24-week) SHC rats and compared these with age-matched Sprague-Dawley rats. In young SHC rats, urinary excretion of hydroxyproline and serum levels of calcium were significantly elevated and excretion of protein into urine and urea nitrogen in the serum were normal, suggesting that calcium metabolism was abnormal without kidney dysfunction at this age. Serum growth hormone and thyroid-stimulating hormone levels were markedly higher (20- to 30-fold and 4- to 5-fold, respectively) in young and old SHC rats, whereas serum prolactin levels were similar. A high level of serum thyroid-stimulating hormone was associated with elevated levels of thyroxine and triiodothyronine in young SHC rats, but not old ones. These results demonstrate that the rat exhibits abnormalities in endocrine function as well as calcium metabolism preceding the occurrence of renal dysfunction. PMID- 2922410 TI - Blunted responses to vasoconstrictors in mesenteric vasculature but not in portal vein of spontaneously hypertensive rats treated with relaxin. AB - Relaxin (RLX), an ovarian polypeptide hormone that is particularly associated with gestation in viviparous species, has recently been shown to decrease blood pressure in virgin spontaneously hypertensive rats (SHR) upon chronic infusion. In this investigation, vascular reactivity to angiotensin II, arginine vasopressin, and norepinephrine was studied in the perfused mesenteric artery and isolated portal vein of control and RLX-treated virgin spontaneously hypertensive rats. The latter received an intravenous infusion of 75 ng/hr purified rat RLX for 2 days, whereas the controls were given an equal infusion of saline. All of the animals were then killed and their tissues processed for in vitro study. In the perfused mesenteric artery, the concentration-response curves for arginine vasopressin and norepinephrine were shifted to the right by a factor of about 2 (P less than 0.05 and P less than 0.005, respectively) after RLX treatment. In the isolated portal vein, the response to angiotensin II was not affected; the effect of norepinephrine was slightly displaced to the right (increase in EC50) and the maximum response remained unchanged. These results demonstrate that RLX treatment for 42 hr blunted the vascular response to vasoconstrictor agents in the mesenteric vasculature and are consistent with similar observations reported previously in the same tissue of 20-day-old pregnant rats. It is concluded that RLX may be involved in the blunted response to vasoconstrictor agents during gestation in the rat. PMID- 2922411 TI - Blood flow distribution with adrenergic and histaminergic antagonists. AB - Superficial fibular nerve stimulation (SFNS) causes increased pre- and post capillary resistances as well as increased capillary permeability in the dog hind paw. These responses indicate possible adrenergic and histaminergic interactions. The distribution of blood flow between capillaries and arteriovenous anastomoses (AVA) may depend on the relative effects of these neural inputs. Right hind paws of anesthetized heparinized dogs were vascularly and neurally isolated and perfused with controlled pressure. Blood flow distribution was calculated from the venous recovery of 85Sr-labeled microspheres (15 microns). The mean transit times of 131I-albumin and 85Sr-labeled microspheres were calculated. The effects of adrenergic and histaminergic antagonists with and without SFNS were determined. Phentolamine blocked the entire response to SFNS. Prazosin attenuated increases in total and AVA resistance. Yohimbine prevented increased total resistance, attenuated the AVA resistance increase, and revealed a decrease in capillary circuit resistance. Pyrilamine attenuated total resistance increase while SFNS increased capillary and AVA resistances. Metiamide had no effect on blood flow distribution with SFNS. The increase in AVA resistance with SFNS apparently resulted from a combination of alpha 1 and alpha 2 receptor stimulation but not histaminergic effects. PMID- 2922412 TI - Effect of age and growth rate on myocardial irritability in broiler chickens. AB - Young broiler chickens are undergoing a period of extremely rapid growth and may be expected to be in a state of extreme endocrine and biochemical flux. These birds are also subject to a sudden death syndrome of unknown etiology. We hypothesized that an increased myocardial sensitivity in birds exhibiting early rapid growth may contribute to this syndrome. The objective of the current study was to investigate the interaction between early growth rate and age on myocardial irritability in young broiler chickens. This study utilized 74 male broiler chickens between 3 (Group A, 21-24 days) and 6 (Group B, 43-47 days) weeks of age exhibiting rapid (heavy weight, greater than 425 g at 2 weeks) and slow (low weight, less than 350 g at 2 weeks) early growth. Physiologic parameters such as blood pressure, heart rate, and arterial blood gases in the awake, restrained birds were essentially unchanged across these groups. Myocardial irritability of the anesthetized bird (pentobarbital) as measured by the threshold to electrical fibrillation was significantly increased only in the Group A HW birds. The results of this study suggest an increased myocardial irritability in large young broilers (3 weeks of age) that is no longer present in a similar group of older birds (6 weeks of age). These findings are consistent with the hypothesis that there is an increased myocardial sensitivity in birds succumbing to sudden death syndrome, with death due to myocardial fibrillation. Further research is needed to determine the mechanisms involve. PMID- 2922413 TI - Are you looking forward to the future? PMID- 2922414 TI - What is an alcohol problem? PMID- 2922415 TI - How would mandatory continuing education work? PMID- 2922416 TI - Women's experiences of gynaecology. PMID- 2922417 TI - Reusable or disposable theatre linen--which is best? PMID- 2922418 TI - Department of Health research studentships. PMID- 2922419 TI - Teaching patients to cope with catheters at home. PMID- 2922420 TI - Dietary restriction and aging. PMID- 2922421 TI - Effect of dietary restriction and aging on lymphocyte subsets in germfree and conventional Lobund-Wistar rats. PMID- 2922422 TI - C-reactive protein in aging Lobund Wistar rats. PMID- 2922423 TI - The effect of dietary restriction on serum hormone and blood chemistry changes in aging Lobund-Wistar rats. PMID- 2922424 TI - Age-related changes in adrenal catecholamine levels and medullary structure in male Lobund-Wistar rats. PMID- 2922426 TI - Adenohypophysial changes in conventional, germ free and food-restricted aging Lobund-Wistar rats. A histologic, immunocytochemical and electron microscopic study. AB - The pituitaries of aging male Lobund-Wistar rats were investigated by histology, immunocytochemistry and electron microscopy. In contrast to previous studies undertaken on aging rats of various strains, no lactotroph hyperplasia was found in the adenohypophysis of the present study. Lactotroph adenomas producing PRL were infrequent, whereas gonadotroph adenomas containing FSH and LH were common. The frequency of gonadotroph adenomas was decreased in germ free as well as food restricted rats and in those in which the germ free state was associated with reduced food intake. PMID- 2922425 TI - Modest dietary restriction and serum somatomedin-C/insulin like growth factor-I in young, mature and old rats. PMID- 2922427 TI - The morphology of adenohypophysial cells in aging Lobund-Wistar rats in tissue culture: an ultrastructural study. PMID- 2922428 TI - Effect of dietary restriction on gastrointestinal cell growth. PMID- 2922429 TI - Fatty acid compositional changes in germfree and conventional young and old rats. PMID- 2922430 TI - Functional and biochemical parameters in aging Lobund-Wistar rats. PMID- 2922431 TI - Blood glutathione: a biochemical index of life span enhancement in the diet restricted Lobund-Wistar rat. AB - These experimental results demonstrate that dietary restriction in both conventional and germfree rats results in enhanced longevity compared to fullfed animals. This increase in median survival age was due to a delay of 8 months in the onset of mortality in the restricted rats. Thereafter the aging rates of the short-lived subpopulations were the same for both groups. However, the aging rate of the long-lived restricted subpopulation was greater. The blood glutathione profiles demonstrated that a GSH deficiency of aging occurred in both the restricted and the long-lived groups. These data confirmed in the rat the findings observed previously in mosquito, mouse and man and verified the generality of the GSH and longevity relationship. Of special interest is that the blood glutathione levels were consistently higher at all ages of the restricted compared to fullfed rats and decreased more slowly during senescence. These findings indicate a direct relationship between enhanced GSH status and increased longevity due to dietary restriction. Further this suggests that glutathione may be a molecular mechanism for the diet restriction and longevity phenomenon. PMID- 2922432 TI - Cellular antioxidant defense system. PMID- 2922433 TI - The role of oxidative modification in cellular protein turnover and aging. PMID- 2922434 TI - The design of the Lobund Aging Study and the growth and survival of the Lobund Wistar rat. PMID- 2922435 TI - Spontaneous diseases in aging Lobund-Wistar rats. PMID- 2922436 TI - Effects of dietary restriction on body composition and body size in germfree and conventional Lobund-Wistar rats. PMID- 2922437 TI - Cardiac fibrosis in the aged germfree and conventional Lobund-Wistar rat. PMID- 2922438 TI - Aging: where we have been and where we are going. PMID- 2922439 TI - Effects of aging, diet restriction and microflora on oral health in humans and animals. PMID- 2922440 TI - How does dietary restriction retard diseases and aging? PMID- 2922442 TI - Structural brain abnormalities in patients with bulimia nervosa. AB - Computed tomographic (CT) brain scans were performed in 50 inpatients with bulimia nervosa, 50 anorectic inpatients, and 50 age-matched control subjects. A number of patients with bulimia nervosa had enlarged ventricles and/or sulcal widening, but the degree and frequency of ventricular dilatation and sulcal widening were not so pronounced as in patients with anorexia nervosa. As the bulimic patients were of normal body weight, the CT abnormalities cannot be attributed to emaciation, which has often been suggested as the cause of abnormalities found in anorectic patients. Since many bulimic patients repeatedly attempt to lose weight by going on restrictive diets, the morphological brain alterations may reflect the endocrine and metabolic reactions to starvation- regardless of whether starvation has led to emaciation, as in the case of anorexia nervosa, or only counterbalanced the binges of high-caloric food. This assumption is supported by the finding that in both bulimic and anorectic patients ventricular size is inversely correlated with the plasma levels of triiodothyronine, a low concentration of which is an indicator for starvation. PMID- 2922441 TI - Comparison of EEG sleep measures among depressive subtypes and controls in older individuals. AB - Psychobiological research has been used to validate subtypes of affective disorder. Nosologic separation of delusional from nondelusional depression has recently been aided by sophisticated analyses of sleep electrophysiology. In the present study, the sleep of elderly delusional and nondelusional depressed patients could be successfully distinguished from that of aged controls using standard sleep parameters. However, only a combination of manual and spectral analytic techniques separated the depressive subtypes. These results are preliminary and need replication in a larger sample. PMID- 2922443 TI - Regional cerebral blood flow during alcoholic blackout. AB - Regional cerebral blood flow was measured during alcoholic blackout in a 61-year old man with a blood-alcohol level of 0.38%. The mean flow level was found to be elevated by about 30-60% compared to repeated studies during long-term abstinence. The regional pattern did not change greatly. Increases of mean regional cerebral blood flow have previously been reported during social drinking and in Wernicke-Korsakoff's syndrome. A common disturbance of subcortical activation systems is hypothesized. PMID- 2922444 TI - Blood platelet uptake of serotonin in episodic aggression. AB - Blood platelet uptake of 3H-serotonin (5HT uptake), a potential marker of serotonergic function, was determined in male outpatients with episodic aggression (n = 15) and in age- and sex-matched nonaggressive controls (n = 15). Correlations with rating scales of "impulsivity" (Barratt Impulsivity Scale, 10th revision) and "anger" (Spielberger Anger Expression Scale) were performed. Mean 5HT uptake was 18% lower in patients with episodic aggression. A significant negative correlation between % difference in platelet 5HT uptake and impulsivity score was observed, but the correlation between 5HT uptake and anger was not significant. These results support the hypothesis of disturbed serotonergic function in aggression and suggest that the primary relationship is in the "control" of aggression. The blood platelet may be useful in identifying impulsive subtypes. PMID- 2922445 TI - Sex roles and regional cerebral blood flow. AB - Several investigators have reported higher resting cerebral blood flow (CBF) in females as compared to males. The relationship between sex roles as quantified by Bem's Sex Role Inventory and CBF was evaluated in 106 right-handed, physically and mentally healthy, drug-free volunteers. CBF was measured noninvasively with the 133xenon inhalation technique. The CBF values correlated inversely with age and positively with carbon dioxide levels, confirming previous reports. Females obtained significantly higher CBF values than males; the differences tended to be most obvious in frontal regions. Males and females who scored high on femininity showed higher CBF as compared to low-femininity subjects even after the effect of sex was covaried out. High masculine sex role tended to be associated with lower CBF, but the effect was less clear. PMID- 2922446 TI - Pseudocholinesterase in obsessive-compulsive patients. AB - Levels of pseudocholinesterase (PsChe) were measured in 20 patients with obsessive-compulsive disorder (OCD) and 20 healthy volunteers. The OCD group had significantly higher PsChe serum activity than in their sex- and age-matched control group. Patients' scores on the Hamilton Rating Scale for Anxiety (HRS-A) and the Beck Depression Inventory (BDI) were not correlated with their PsChe levels. The results provide additional support for the observation of higher PsChe levels among anxiety-related psychiatric conditions. However, the relationships among anxiety, depression, and PsChe appear to be complex. The nature and implications of elevated PsChe levels are still unknown. PMID- 2922447 TI - Is there a relation between the seriousness of suicidal intent and the lethality of the suicide attempt? AB - The relation between the strength of an individual's intent to commit suicide and the nature and seriousness (lethality) of any suicide attempt has been a controversial one. Some studies suggest a positive correlation, while others report no connection. The present investigation included 60 patients, who were studied shortly after they had been admitted to a medical service after a suicide attempt. Measures of depression, impulsivity, suicidal intent, seriousness of the attempt, and efforts to prevent intervention were obtained. Results reveal that both depression and impulsivity correlate positively with the strength of the intent to commit suicide, but there appears to be almost no correlation in this population between measures of intent and seriousness of the attempt. PMID- 2922448 TI - Platelet MAO activity and personality variations in normals. AB - The authors examined platelet MAO activity and several personality variables in 58 non-clinic-referred healthy adult males. The psychological tests administered consisted of the Minnesota Multiphasic Personality Inventory, the Personality Research Form-E, and the Zuckerman Sensation Seeking Scale. The findings replicated previous findings in the literature. PMID- 2922449 TI - A Visual Analogue Scale technique to measure global vigor and affect. AB - This article describes an easily administered Visual Analogue Scale (VAS) technique that can be used to detect changes in mood and subjective activation. The method yields two summary measures: Global Vigor (GV) and Global Affect (GA), each ranging in value from 0 to 100. The instrument was administered about six times per day in 38 healthy control and 6 depressed patients participating in temporal isolation studies. This yielded a total of 5,734 control subject sessions and 575 patient sessions. For both groups, frequency distributions of GV and GA were shown to be approximately Gaussian, and evidence was obtained suggesting that the instrument was being completed properly. On average, depressives were about 0.6 standard deviations lower than controls in GV and about 1.5 standard deviations lower in GA, confirming the validity of the scales. Measures of GV in controls were shown to be sensitive to both jet lag and diurnal variation, thus confirming the reliability and validity of GV in these situations. In two studies involving more than 50 days of voluntary seclusion, measures of GA were found to show an almost monotonic decline, tracking the decline in mood and confirming the reliability and validity of GA in that situation. PMID- 2922450 TI - A psychometric study of surface electrode placements for facial electromyographic recording: I. The brow and cheek muscle regions. AB - Despite the burgeoning literature using facial electromyography (EMG) to study cognitive and emotional processes, the psychometric properties of facial EMG measurement have received little attention. Two experiments were conducted to assess the reliability and validity of facial EMG as a measure of specific facial actions. In Experiment 1, two recording sites in the brow region were compared for their ability to differentiate facial actions hypothesized to be due to the activation of the corrugator supercilii from facial actions presumed to be due to the activation of proximate muscles (e.g. depressor supercilii, procerus, frontalis, levator labii superioris alaeque nasi, orbicularis oculi), and four sites in the infraorbital triangle were compared for their ability to differentiate facial actions hypothesized to be due to the activation of the zygomaticus major from facial actions presumed to be due the activation of proximate muscles (e.g. zygomaticus minor, risorius, buccinator, orbicularis oculi, orbicularis oris). Fifteen subjects were instructed to pose a series of facial actions while EMG activity was sampled simultaneously at all sites. In Experiment 2, 5 subjects returned to the laboratory for a more extensive investigation of surface EMG activity over the zygomaticus major muscle region. The results of this experiment confirmed the findings of Experiment 1. Overall, the results demonstrate that certain recording sites located over specific facial muscle regions are more sensitive and valid indices of particular facial actions than other nearby sites. PMID- 2922451 TI - The relationship between the type A behavior pattern and physiological responsivity: a quantitative review. AB - Researchers have attempted to specify the process linking Type A behavior to coronary artery disease. Increased cardiovascular and neuroendocrine reactivity in Type A individuals has been proposed as the intervening mechanism. There have been several previous reviews of the research relating Type A behavior to physiological reactivity. The authors' conclusions have been equivocal; some assert that Type A persons are more reactive, whereas others find no evidence for such a conclusion. In this report, meta-analysis, an alternative to the traditional narrative review, was employed to provide a quantitative evaluation of the relationship between Type A behavior and physiological reactivity. Results indicated that: 1) Type As respond to cognitive and psychomotor stimulus situations with greater heart rate and systolic blood pressure responses, 2) this relationship is not evident in females, 3) the relationship is more evident for some cognitive tasks than for others, and 4) the strength of the relationship depends upon the instrument used to assess Type A behavior. PMID- 2922452 TI - The law of initial values: differentiated testing as an empirical generalization versus enshrinement as a methodological rule. PMID- 2922453 TI - Aerobic fitness and the cardiovascular response to stress. AB - The observation that aerobically fit persons react to physical load with a smaller sympathetic response than do less fit subjects suggests that their response to psychological stress might also be reduced. The evidence for this, however, is far from consistent. It was argued that this inconsistency might be due to the incomplete measurement of the response system involved. In the present experiment two groups, which differed strongly in maximal aerobic power, were compared with respect to their cardiovascular response to a laboratory stressor. In addition to the traditional heart rate and blood pressure measurements, pre ejection period, cardiac output, and peripheral resistance were assessed. Since only the part of the stress response that is not accounted for by metabolic needs might have pathological significance, the so-called "additional" responses were also measured. Fitness was shown to be associated with smaller sympathetic effects on both heart and vessels. The decrement in pre-ejection period and the heart rate response were smaller in the high fit group. The total peripheral resistance and diastolic blood pressure responses pointed to a much stronger vascular reactivity in the low fit group. Unexpectedly cardiac output did not increase during stress. The strong heart rate response in the low fit group was compensated by a reduction in stroke volume, which probably originated in an increased peripheral resistance. The largest discrepancy between the effects of sympathetic activation during stress and exercise occurred in the vessels, as demonstrated by the large "additional" response in total peripheral resistance during stress. The data point to the often neglected role of vascular processes in experiments of this kind. Furthermore, it seems necessary to take the effect of fitness into account when comparing subjects with respect to their cardiovascular stress response. PMID- 2922454 TI - Stimulus novelty and significance as determinants of electrodermal responsivity: the serial position effect. AB - Three experiments examined the effects of stimulus novelty and significance on the skin conductance component of the orienting response. The test stimuli used in the different experiments involved either a neutral change in stimulation (i.e., adding or deleting components to the standard stimuli), or an introduction of a significant element to the standard stimulus. The serial position of the test stimulus was manipulated in all three experiments. In Experiment 1, nonsignificant test stimuli were introduced at the second, fourth, sixth, or eighth trial of the complex sequence of eight stimuli (i.e., a sequence comprised of varying standard stimuli). None of the test stimuli produced enhanced skin conductance responses under these conditions. Experiment 2 utilized the same design with only one difference: the test stimuli were presented following a simple stimulus sequence (i.e., repetition of a fixed standard stimulus). In this design enhanced skin conductance responses to the test stimuli were observed in almost all experimental conditions, with an advantage of a late over an early presentation of the test stimulus. Experiment 3 was designed to compare serial position effects of significant and neutral test stimuli. A serial position effect was obtained only for the neutral test stimuli, showing once again an advantage for late presentations. It was suggested that different mechanisms might underlie skin conductance responses to significant stimuli and to novel neutral stimuli. PMID- 2922455 TI - Race, parental history of hypertension, and patterns of cardiovascular reactivity in women. AB - This study examined the interaction of race and parental history of hypertension on patterns of cardiovascular responses among women. Two stressors were used that produce different patterns of cardiovascular reactivity: mental arithmetic, primarily a beta-adrenergic stimulus, and the cold face stimulus, which evokes alpha-adrenergic (i.e. vascular) activity. Systolic and diastolic blood pressure, heart rate, forearm blood flow, and forearm vascular resistance were assessed before, during, and after arithmetic and cold face stimulus. Both tasks produced the expected patterns of cardiovascular adjustment, although no Black-White differences occurred during arithmetic. However, Black subjects did show a slower recovery of diastolic blood pressure following arithmetic. The cold face stimulus produced significantly greater changes in systolic blood pressure in the Black than in the White women. Parental history of hypertension did not relate significantly to reactivity. The results provide limited support for the idea that Black females exhibit a greater pressor response than White females to a stimulus that produces primarily vascular rather than cardiac changes. These findings are discussed in relation to previous findings with males and with respect to their implications for the role of reactivity in Black-White differences in hypertension prevalence. PMID- 2922456 TI - Orienting in schizophrenia: habituation to auditory stimuli of constant and varying intensity in patients high and low in skin conductance responsivity. AB - Groups of schizophrenics and normal controls were exposed to different series of tones of constant (80dB) and variable intensity (60, 80, and 100 dB). Measurements included bilateral skin conductance, finger pulse volume, and heart rate. Both groups were split on the common median in skin conductance response to constant intensity tones to form matched patient and control groups of low and high responsivity. The low and high responsive schizophrenic groups were more clearly separated than the two control groups in rate of spontaneous skin conductance fluctuations, skin conductance magnitudes, and skin conductance levels, primarily because of generalized hyperactivity in high responsive patients. This pattern was clearest for the most intense tone and left hand recordings. High responsive schizophrenics also showed larger response amplitudes, shorter rise and recovery times, and a smaller ratio of elicited to spontaneous responses, than high responsive controls. Finger pulse volume responses recorded from the left hand were smaller in the patient groups, whereas patients and controls did not differ in right hand recordings. High skin conductance responsive subjects showed more heart rate deceleration than low responsive subjects, and schizophrenics had more decelerative responses than controls. PMID- 2922457 TI - Stability of myoelectric slow waves and contractions recorded from the distal colon. AB - The stability of physiological activity in the distal colon was investigated by recording 5-6 hours in each of 6 healthy adults. Contractions and myoelectric slow waves were recorded from the sigmoid colon (25-30 cm from the skin surface) and rectum (10-15 cm), and pressure waves were recorded from the proximal small intestine. The activity index (sum of areas of all waves divided by recording time) varied by 200% to 800% across 4-min samples for all motility and myoelectric slow wave recordings. Spectral analysis indicated that contractile activity waxed and waned in a cycle with a period of 40-55 min in the colon and 64-80 min in the small intestine. Myoelectric slow wave activity in the colon cycled with a period of 30-40 min. Contractile activity in the sigmoid colon was correlated with similar activity in the rectum, but myoelectric slow wave activity in the colon was not correlated with myoelectric slow waves in the rectum. The frequency composition of contractions and slow waves was unstable over time. PMID- 2922458 TI - Does the heart know what the eye sees? A cardiac/pupillometric analysis of motor preparation and response execution. AB - Autonomic response measures are well suited for the study of preparation because they allow the analysis of covert aspects of performance. This is illustrated by an experiment in which task-evoked cardiac and pupillary responses were compared during a disjunctive (Go/No Go) reaction task. The motoric demands of the task were varied by manipulating foreperiod length (4 and 8 s) and probability of response (25%, 50%, and 75%). Reaction time increased with foreperiod length and decreased with probability of response. The depth of anticipatory heart rate deceleration was affected only by foreperiod length. Analysis of the beats during, and directly preceding and following the imperative stimulus revealed that interbeat intervals increased with probability of responding and foreperiod duration. The effect of stimulus timing relative to the R-wave of the ECG was also analyzed. Early occurring stimuli prolonged the cycle of their occurrence more than late occurring stimuli. The cycle time effect was somewhat more pronounced for No Go stimuli than for Go stimuli. The subsequent cycle was shorter for early occurring stimuli compared to late stimuli. This effect was stronger for Go compared to No Go trials. Both Go and No Go reactions elicited significant pupil dilations. The No Go dilation peaked earlier than the Go dilation and its amplitude was smaller. Probability of responding affected the latency of the No Go dilation but not that of the Go dilation. The current results justify an interpretation of preparation in terms of a timing mechanism (indexed by heart rate deceleration during the foreperiod) and a mechanism allocating processing resources to stimulus encoding (indexed by cardiac slowing just prior to stimulus occurrence) and response preparation (indexed by continued cardiac deceleration and pupillary dilation). PMID- 2922459 TI - Components of type A behavior and task-induced cardiovascular activation. AB - The present study sought to determine whether there are subcomponents of the Type A behavior pattern that are more closely related to cardiovascular reactivity than others. The components studied were factor analytically derived subscales of the Jenkins Activity Survey denoting Irritation and Impatience, on the one hand, and Hard-Driving and Competitive, on the other. Heart rate, pulse transit time, forearm electromyography, and palmar skin conductance were measured while the subjects performed a continuous perceptual motor task, as well as during baselines before and after the task. The Irritation and Impatience dimension was consistently related to task-induced changes in heart rate, both in regression analyses and in extreme group analyses of variance. A significant relation was also observed for pulse transit time but not for electromyography. The Hard Driving and Competitive dimension, on the other hand, was not related to any psychophysiological measures. These results were interpreted to mean that Irritable and Impatient subjects showed a cardiovascular reaction pattern indicative of active coping processes during task performance. PMID- 2922460 TI - Attention to color: an analysis of selection, controlled search, and motor activation, using event-related potentials. AB - In this study the organization of information processing in a selective search task was examined by analyzing event-related potentials. This task consisted of searching for target letters in a relevant (attended) color. The ERPs revealed two different effects of attention: an early occipital negativity (+/- 150 ms) reflecting feature-specific attention, and a later, central N2b component (+/- 240 ms) reflecting covert orienting of attention. A later, prolonged negativity (search-related negativity) (+/- 300 ms), maximal at Cz, was related to controlled search to letters in the attended color. Detection of relevant targets resulted in a parietal P3b component. Depending on stimulus presentation conditions an earlier response to both attended and unattended targets was found: an N2 component (+/- 250 ms). In these same conditions, C'3-C'4 asymmetries (Corrected Motor Asymmetries--CMA) suggested motor activation at +/- 300 ms, in the same time range as search-related negativity. It was argued that N2 and CMA suggest the existence of a preattentive target detection system, operating in parallel with a slower serial attentive system, as reflected by N2b and search negativity. PMID- 2922461 TI - Nursing no place to scrimp on health care cost. PMID- 2922462 TI - Radiation litigation in retrospect. AB - Most of the radiation litigation filed against the United States pursuant to the Federal Tort Claims Act has been defended by asserting federal sovereign immunity or by proving that the plaintiff's injury is unrelated to his radiation exposure. This paper reports that the second defense is best advanced by comprehensive pretrial investigation of the plaintiff's claim, which frequently results in voluntary dismissal of the legal action. PMID- 2922463 TI - The role of the expert witness. PMID- 2922464 TI - Radiation litigation: future issues. AB - Scientists and regulators have successfully been able to control exposures to man made ionizing radiation so that mankind has been able to enjoy its vast benefits without experiencing the significant harm which would occur from high doses. However, thousands of lawsuits have been filed claiming that low occupational levels of ionizing radiation have caused cancer and other illnesses. It will be decades before the legal system determines the rules of law which will apply to this new type of lawsuit and the effects which these cases will have upon those persons who work with sources of ionizing radiation. This article explores some of the issues which are expected to arise as these cases work their way through the courts. PMID- 2922465 TI - The effect of gamma radiation on DNA methylation. AB - The effect of 60Co gamma radiation on DNA methylation was studied in four cultured cell lines. In all cases a dose-dependent decrease in 5-methylcytosine was observed at 24, 48, and 72 h postexposure to 0.5-10 Gy. Nuclear DNA methyltransferase activity decreased while cytoplasmic activity increased in irradiated (10 Gy) V79A03 cells as compared to controls. No DNA demethylase activity was detected in the nuclei of control or irradiated V79A03 cells. Additionally, gamma radiation resulted in the differentiation of C-1300 N1E-115 cells, a mouse neuroblastoma line, in a dose- and time-dependent manner. These results are consistent with the hypothesis that (1) genes may be turned on following radiation via a mechanism involving hypomethylation of cytosine and (2) radiation-induced hypomethylation results from decreased intranuclear levels of DNA methyltransferase. PMID- 2922466 TI - Proportionality of 60-Hz electric field bioeffect severity to average induced transmembrane potential magnitude in a root model system. AB - The postulate that electric field-induced bioeffects in the root model system are related to the induction of 60-Hz transmembrane potentials (Vim) was quantitatively tested. Root segment growth rate data and the calculated mean 60 Hz Vim which would arise in the cortical cells of a segment under specified exposure conditions were subjected to regression analysis. Statistically significant correlations between segmental growth rate and segmental-average Vim were obtained using data analyzed (1) within species at a constant applied field strength, (2) within species and pooled across field exposures, and (3) pooled across both species and exposures. In C. sativus roots, segmental growth is inhibited when segmental-average Vim attain a value of 3.4-3.6 mV. In C. maxima roots, growth inhibition occurs when Vim attain or exceed 2.3-2.7 mV. Segmental growth cessation is predicted to occur when segmental-average Vim exceed 7-9 mV. PMID- 2922467 TI - Analysis of structural and numerical chromosomal aberrations at the first and second mitosis after X irradiation of two-cell mouse embryos. AB - Two-cell mouse embryos were X-irradiated in the late G2 phase in vivo. The first and second postradiation mitoses were analyzed for chromosomal anomalies. The majority of structural aberrations visible at the first mitosis after irradiation were chromatid breaks and chromatid gaps; only a few interchanges and dicentrics were observed. The aberration frequency resulted in a dose-effect relationship which was well described by a linear model. At the second mitosis 29% of the structural aberrations of the first mitosis were counted; the aberration quality changed only slightly. It is discussed whether these aberrations are to be considered "new," "derived," or unchanged transmitted aberrations. Contrary to the results obtained after irradiation of one-cell embryos, little chromosome loss was induced by radiation in two-cell embryos. PMID- 2922469 TI - Chromatin decondensed by acetylation shows an elevated radiation response. AB - V-79 Chinese hamster lung fibroblasts exposed to 5 mM n-sodium butyrate were irradiated with 60Co gamma rays and cell survival was determined by the cell colony assay. In a separate set of experiments the acetylated chromatin obtained from these cells was irradiated and the change of molecular weight of the DNA was evaluated by alkaline sucrose density centrifugation. At a survival level of 10( 2) to 10(-4) cells exposed to butyrate were found to be 1.3-1.4 times more radiosensitive than control cells. Exposure of isolated chromatin to 100 Gy of 60Co gamma irradiation generated 0.9 +/- 0.03 single-strand breaks (ssb) per 10 Gy per 10(8) Da and 2.0 +/- 0.3 ssb/10 Gy/10(8) Da for control and acetylated chromatin, respectively. The elevated radiation sensitivity of chromatin relaxed by acetylation is in good agreement with previous results on chromatin expanded by histone H1 depletion [Heussen et al., Radiat. Res. 110, 84-94 (1987)]. Packing and accessibility of DNA in chromatin appear to be major factors which influence the radiation sensitivity. The intrinsic radiation sensitivity of chromatin in various packing states is discussed in light of the variation of radiation sensitivity of whole cells in the cell cycle which incorporates repair. PMID- 2922468 TI - Radiation-induced association of beta-glucuronidase with purified nuclei from irradiated MOLT-4 and HeLa cells. AB - Beta-glucuronidase, a lysosomal marker enzyme, associates with purified nuclei from HeLa and MOLT-4 cell lines in a radiation dose-dependent manner, up to 300 cGy in MOLT-4 cells, and 1000 cGy in HeLa cells. In MOLT-4 cells (200-cGy exposure), there is a significant increase in beta-glucuronidase activity detected in the nuclear fraction 24 h postirradiation with a maximum association occurring at 72 h. In HeLa cells (1000-cGy exposure), a significant association is first detected 24 h postirradiation with a maximum association at 48 h. The association is not the result of nonspecific contamination occurring during nuclei purification since nuclei from irradiated cells show no greater levels of plasma membrane marker and mitochondrial marker than controls. The nature of the association remains unclear, but activity is not removed by detergents used in the nuclei isolation procedure, and incubation of the nuclei with EDTA reverses the association only modestly. Exposure of nuclei from irradiated cells to anisotonic buffers also results in only a small decrease in beta-glucuronidase activity associated with the nuclei. These observations suggest that lysosomal hydrolases become intimately associated with the nuclei of irradiated cells. PMID- 2922470 TI - Radiobiological intercomparison of clinical neutron beams for growth inhibition in Vicia faba bean roots. AB - Relative biological effectiveness (RBE) and oxygen enhancement ratio (OER) values of different neutron beams produced at the variable energy cyclotron "Cyclone" of Louvain-la-Neuve (Belgium) were determined. The neutrons were obtained by bombarding a beryllium target with 34-, 45-, 65-, or 75-MeV protons or with 50 MeV deuterons. The biological system was growth inhibition in Vicia faba bean roots. Taking the p(65) + Be neutron beam as a reference, RBE values were found equal to 1.36 +/- 0.2, 1.20 +/- 0.1, 1.00 (ref), 0.98 +/- 0.1, and 1.18 +/- 0.1, respectively; the doses corresponding to 50% growth inhibition were 0.39, 0.44, 0.53, 0.54, and 0.45 Gy. For the same beams, OER values were found equal to 1.55 +/- 0.1, 1.38 +/- 0.1, 1.29 +/- 0.1, 1.41 +/- 0.1, and 1.60 +/- 0.2, respectively. PMID- 2922471 TI - Protection against radiation-induced mutagenesis in V79 cells by 2 [(aminopropyl)amino] ethanethiol under conditions of acute hypoxia. AB - The effects of the radioprotector 2-[(aminopropyl)amino] ethanethiol (WR-1065) on radiation-induced cell killing and mutagenesis at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus in V79 Chinese hamster cells under hypoxic or aerobic conditions were examined. Conditions of acute hypoxia were attained by gassing 10(6) cells in 1-ml volumes in individual glass ampoules for 2 min with nitrogen. Ampoules were then sealed and incubated at 37 degrees C for 60 min. Following this treatment, cell survival after irradiation as expected was significantly enhanced. The effect of acute hypoxia on the formation of HGPRT mutants by irradiation was also investigated. Mutation frequencies were determined with a 6-day expression time and corrected for the number of spontaneous background mutants. Although mutation induction was approximately linear as a function of radiation dose under most conditions tested, it was significantly reduced in cell populations made acutely hypoxic prior to irradiation. Protection against mutation induction was apparent and similar when cells were irradiated in the presence of the radioprotector, regardless of whether they were also hypoxic or aerated. If cells were irradiated in air and then made hypoxic, no significant protection was still observed. These results suggest that the antimutagenic effect of WR-1065 is not due solely to its ability to scavenge radiation-induced oxygen-free radicals, but rather that it may also modulate these effects through the scavenging of metabolically induced free radicals and/or the chemical repair of radiation-induced DNA lesions. PMID- 2922472 TI - Combined effects of radiation and caffeine on embryonic development in mice. AB - The combined effect of radiation and caffeine has been studied in mouse embryos. Radiation and/or caffeine were administered to ICR mice on Day 11 of gestation. Intrauterine death, gross malformation, and fetal body weight were selected as indicators of effects. Doses of whole-body gamma irradiation were 0.5 to 2.5 Gy and those of caffeine were 100 and 250 mg/kg maternal body wt. Intrauterine mortality increased with increasing radiation dose; this trend was more remarkable in combination with caffeine. Gross malformations such as cleft palate and defects of forelegs and hindlegs appeared frequently in the fetuses treated with both radiation and caffeine. Decreased fetal weight was observed even in mice treated with 0.5 Gy of radiation or 100 mg/kg caffeine. There was a linear relationship between dose and reduction of fetal weight. The fetal weight was a sensitive, precise, and easy-to-handle indicator for the effects of growth retardation. Intrauterine mortality and frequencies of cleft palate and defects of forelegs and hindlegs were higher than the sum of those induced by radiation and by caffeine separately. The results indicated that the combined action of radiation and caffeine on intrauterine death and malformations was synergistic. PMID- 2922473 TI - pH-dependent effects of the ionophore nigericin on response of mammalian cells to radiation and heat treatment. AB - The extracellular pH (pHe) in many solid tumors is often lower than the pH of normal tissues. The K+/H+ ionophore nigericin is toxic to CHO cells when pHe is below but not above 6.5, and thus it has potential for selective killing of tumor cells in an acidic environment. This study examines the pH-dependent effects of nigericin on the response of CHO cells to radiation and heat treatment. Cells held for 4 h in Hank's balanced salt solution, after 9 Gy irradiation, exhibit potentially lethal damage recovery (PLDR) which is maximal at pHe 6.7-6.8. Addition of nigericin, postirradiation, not only inhibits PLDR when pHe is below 6.8, but interacts synergistically with radiation to reduce survival below that of cells plated immediately after irradiation when pHe is 6.4 or lower. Nigericin enhances heat killing of CHO cells perferentially under acidic conditions, and where neither heat nor drug treatment alone is significantly toxic. Survival of cells held for 30 min at 42.1 degrees C in the presence of 1.0 microgram/ml nigericin is 0.6, 0.08, 0.003, and 0.00003 at pHe 7.4, 6.8, 6.6, and 6.4, respectively, relative to survival of 1.0 in untreated cultures. The biochemical effects of nigericin at pHe 7.4 vs pHe 6.4 have been investigated. Nigericin inhibits respiration, stimulates glucose consumption, and causes dramatic changes in intracellular concentrations of Na+ and K+ at pHe 7.4 as well as 6.4. The drug reduces intracellular levels of ATP, GTP, and ADP but has more pronounced effects under acidic incubation conditions. Others have shown that nigericin equilibrates pHe and intracellular pH (pHi) only when pHe is 6.5 or lower. Our observations and those of others have led us to conclude that lowering of pHi by nigericin is either the direct or indirect cause of enhancement of radiation and heat killing of cells in an acidic environment. PMID- 2922474 TI - Steroid hormone production in testis, ovary, and adrenal gland of immature rats irradiated in utero with 60Co. AB - Pregnant rats received whole-body irradiation at 20 days of gestation with 2.6 Gy lambda rays from a 60Co source. Endocrinological effects before maturation were studied using testes and adrenal glands obtained from male offspring and ovaries from female offspring irradiated in utero. Seminiferous tubules of the irradiated male offspring were remarkably atrophied with free germinal epithelium and containing only Sertoli cells. Female offspring also had atrophied ovaries. Testicular tissue obtained from intact and 60Co-irradiated rats was incubated with 14C-labeled pregnenolone, progesterone, 17 alpha-hydroxyprogesterone, and androstenedione as a substrate. Intermediates for androgen production and catabolic metabolites were isolated after the incubation. The amounts of these metabolites produced by the irradiated testes were low in comparison with the control. The activities of delta 5-3 beta-hydroxysteroid dehydrogenase, 17 alpha hydroxylase, C17,20-lyase, and delta 4-5 alpha-reductase in the irradiated testes were 30-40% of those in nonirradiated testes. Also, the activities of 17 beta- and 20 alpha-hydroxysteroid dehydrogenases were 72 and 52% of the control, respectively. In adrenal glands, the 21-hydroxylase activity of the irradiated animals was 38% of the control, but the delta 5-3 beta-hydroxysteroid dehydrogenase activity was comparable to that of the control. On the other hand, the activity of delta 5-3 beta-hydroxysteroid dehydrogenase of the irradiated ovary was only 19% of the control. These results suggest that 60Co irradiation of the fetus in utero markedly affects the production of steroid hormones in testes, ovaries, and adrenal glands after birth. PMID- 2922475 TI - Apparent synergism between radiation and the carcinogen 1,2-dimethylhydrazine in the induction of colonic tumors in rats. AB - We have evaluated the interaction of radiation and 1,2-dimethylhydrazine (DMH) with respect to colon carcinogenesis in the Fischer 344 rat and have demonstrated the utility of this model for future more detailed mechanistic studies. In initial experiments, single doses of abdomen-only radiation (9 Gy) or DMH (150 mg/kg) were employed alone or in combination. Radiation was administered 3.5 days prior to the DMH. At 8 months post-treatment, the incidence of DMH-induced colon tumors was doubled by prior radiation exposure. When the protocol was repeated employing a DMH dose of 135 mg/kg with a 6-month observation period, the incidence of tumors induced by DMH alone was reduced, but the combination of radiation plus DMH still resulted in an augmentation of tumor incidence. When the protocol of radiation plus DMH was repeated three times at monthly intervals, a 15-fold increase in tumor incidence (from 5 to 74%) was observed at 6 months post treatment. This finding demonstrates an apparent synergy between the radiation and the chemical carcinogen. Throughout these studies, the appearance of carcinomas was associated with preexisting colonic lymphoid nodules. The reproducibility of tumor induction as well as range of tumor incidence generated by variations in this system may be adequately sensitive to examine the combination of much lower doses of radiation and/or chemical carcinogen. The relationship between existing lymphoid aggregates which alter local epithelial cell kinetics and which are associated with fenestrations in the basement membrane, and the development of colon cancer in congruent sites may assist in defining dose-response curves for combined agents as well as providing a system for evaluating the mechanisms underlying their interactions. PMID- 2922476 TI - Selenite-induced variation in glutathione peroxidase activity of three mammalian cell lines: no effect on radiation-induced cell killing or DNA strand breakage. AB - The selenium-dependent glutathione peroxidase activities of three mammalian cell lines, HT29, P31, and N-18, cultured in medium with low serum content, increased about 2-, 5-, and 40-fold, respectively, after supplementation with 100 nM selenite. Catalase, CuZn superoxide dismutase, and Mn superoxide dismutase activities were not generally influenced by selenite supplementation, and there was only a minor nonselenium-dependent glutathione peroxidase activity in the investigated cell lines. Gamma-irradiated control and selenite-supplemented cells showed no changes in the surviving fractions, as estimated by clonogenic survival or [3H]-thymidine uptake, nor were there any significant differences between the two groups in the induction of DNA strand breaks after gamma irradiation under repairing (37 degrees C) or nonrepairing (0 degrees C) conditions. The results suggest that selenium-dependent glutathione peroxidase does not contribute significantly to the radiation resistance of cultured mammalian cells. PMID- 2922477 TI - Radiation-induced endothelial dysfunction and fibrosis in rat lung: modification by the angiotensin converting enzyme inhibitor CL242817. AB - The purpose of this study was to evaluate the angiotensin converting enzyme (ACE) inhibitor CL242817 as a modifier of radiation-induced pulmonary endothelial dysfunction and pulmonary fibrosis in rats sacrificed 2 months after a single dose of 60Co gamma rays (0-30 Gy) to the right hemithorax. CL242817 was administered in the feed continuously after irradiation at a regimen of 60 mg/kg/day. Pulmonary endothelial function was monitored by lung ACE activity, plasminogen activator (PLA) activity, and prostacyclin (PGI2) and thromboxane (TXA2) production. Pulmonary fibrosis was evaluated by lung hydroxyproline (HP) content. Lung ACE and PLA activities decreased with increasing radiation dose, and cotreatment with CL242817 significantly ameliorated both responses. CL242817 dose-reduction factors (DRF) were 1.3-1.5 for ACE and PLA activity. Lung PGI2 and TXA2 production increased with increasing radiation dose, and CL242817 almost completely prevented both radiation responses. The slope of the radiation dose response curves in the CL242817-treated rats was essentially zero, precluding calculation of DRF values for PGI2 and TXA2 production. Lung HP content also increased with increasing radiation dose, and CL242817 significantly attenuated this response (DRF = 1.5). These data suggest that the ability of ACE inhibitors to ameliorate radiation-induced pulmonary endothelial dysfunction is not unique to captopril [Ward et al., Int. J. Radiat. Oncol. Biol. Phys. 15, 135-140 (1988)], rather it is a therapeutic action shared by other members of this class of compounds. These data also provide the first evidence that ACE inhibitors exhibit antifibrotic activity in irradiated rat lung. PMID- 2922478 TI - Halogenated pyrimidines as radiosensitizers for high-LET radiation. AB - The incorporation of iododeoxyuridine (IdUrd) into Chinese hamster cells was examined as a possible radiosensitizer for fission spectrum neutrons. Dose response curves comparing both X rays and neutrons in the same cell line with the same IdUrd replacement showed a similar radiation enhancement for IdUrd incorporation. Enhancement ratios at the 1% survival level were 1.8 for X rays and 1.5 for fission spectrum neutrons. While the mechanism of this enhancement in the response for fission neutron radiation is unclear, these positive data should support further exploration to determine if halogenated pyrimidine incorporation results in sensitization for neutron energies employed in therapy. PMID- 2922479 TI - Satellite colony formation: a potential problem in the quantitative assay for neoplastic transformation of human cell hybrids (HeLa x skin fibroblasts). PMID- 2922480 TI - Oncogenic transformation by fractionated doses of neutrons. PMID- 2922481 TI - Nurse liability in patient transfer. PMID- 2922482 TI - Can nurse "diagnose" arrest of labor? Case in point: Ewing v. Aubert (532 So. 2d 876--LA (1988)). PMID- 2922483 TI - Legal case briefs for nurses. GA.: incident report altered: punitive damages; CO.: concealing death: indictment dismissed. PMID- 2922484 TI - Nurses fail to respond to emergency "stat". Case in point: Garcia v. U.S. (697 F. Supp. 1579--CO (1988)). PMID- 2922485 TI - The hidden fallacies in longitudinal designs. PMID- 2922486 TI - Maternal confidence during toddlerhood: comparing preterm and fullterm groups. AB - The purposes of this study were to explore predictors of maternal confidence during toddlerhood among mothers of children born preterm and fullterm and to determine if mothers of toddlers born preterm were less confident in parenting than mothers of toddlers born fullterm. Mothers of children born preterm (n = 62) and fullterm (n = 70) aged 12 months through 36 months (postnatal age) completed a measure of maternal confidence during toddlerhood, the Toddler Care Questionnaire (TCQ), and a family background form. Major predictor variables included the extent of the mother's prior childcare experience, toddler birth order, and maternal report of toddler handicaps and major health problems. Data on neonatal condition were collected from hospital records. There was no difference in mean TCQ score between the preterm and fullterm groups. In the preterm group, prior childcare experience, birth order, and maternal report of the toddler having cerebral palsy explained 33% of the variance. In the fullterm group, prior childcare experience, maternal age and toddler's birthweight explained 38% of the variance. The findings are discussed in light of Bandura's theory of self-efficacy (1982). PMID- 2922487 TI - Instructional information and breast self-examination practice. AB - The effects of four interventions on frequency and thoroughness of breast self examination (BSE) were compared. The interventions provided different types of information, as derived from a self-regulation framework, to promote BSE practice. Women seeking BSE instruction (N = 204) were randomly assigned to interventions. No intervention effects on frequency were observed. However, exam frequency increased from pre- to postintervention and remained constant over 3 and 6 months follow-up. Interaction effects observed on thoroughness suggested that a positive effect of sensory information about the breast was conditional upon having had prior experience with BSE. Implications for research, theory, and practice are drawn. PMID- 2922488 TI - Confusion in the hospitalized elderly: incidence, onset, and associated factors. AB - Seventy-one non-surgical patients over age 60 years were studied to obtain information about the incidence, onset and variables associated with the onset of confusion. The incidence of confusion was 38%; 27 of the 71 subjects developed confusion during hospitalization. Nineteen of the 27 patients developed confusion by the second day of hospitalization; no new cases of confusion were detected after the sixth day of hospitalization. An examination of the psychophysiologic variables associated with the onset of confusion produced a profile of the confused elderly patient. Confused patients were: hypernatremic, hypokalemic, hyperglycemic, hypotensive, had elevated blood levels of creatinine and urea nitrogen, received more medications, were more frequently perceived by nurses as confused, had more orienting objects in their immediate environment, and fewer interactions with significant others. Recommendations for the continued investigation and care of confused patients are offered. PMID- 2922489 TI - Theoretical modeling to predict violence in hospitalized psychiatric patients. AB - Research from a nursing perspective on factors related to psychiatric inpatient violence is lacking. The purpose of the study was to test a nursing theoretical framework of violence using predictive model testing. Data were collected by 57 nursing staff on 162 hospitalized patients in four hospitals. Inconsistencies in the social and therapeutic rules predicted 18% of the violent behavior. Demographic and medical variables contributing to violence were: history of violence towards others, length of hospitalization, and the diagnosis of substance abuse. The findings support the need for further research to identify nursing concepts that contribute to patient violence. PMID- 2922490 TI - Blood pressure norms for healthy young adults: relation to sex, age, and reported parental hypertension. AB - Blood pressure norms are presented for 1,522 white, healthy, nonsmoking, normotensive 18 to 22-year-old men and women as a function of age and parental hypertension. Age effects were observed for diastolic blood pressure among males only. Parental hypertension was related to higher systolic and diastolic blood pressure among young women, and women with two hypertensive parents had higher systolic blood pressure than women with one hypertensive parent. The use of oral contraceptives is likely to have affected these results. Directions for future research are given. PMID- 2922491 TI - Some ethical implications of qualitative research. AB - Traditional values in nursing dictate a high level of concern for the welfare of research participants. Initial attempts at setting minimal ethical standards stemmed from the quantitative approaches. As qualitative modalities are more widely used, nurses must become acutely aware of possible problems in study design and planning, the dangers of coercion and deception, threats to confidentiality and trust, implications of the emergent design, and providing for a new concept of informed consent. The new character of the research relationship is examined in light of possible strategies for protection of research participants while preserving the integrity of qualitative investigation. PMID- 2922492 TI - Involvement of perivascular neuropeptide Y nerve fibres in uterine arterial vasoconstriction in conjunction with pregnancy. AB - The perivascular neuropeptide Y (NPY) innervation and its relation to adrenergic nerves of uterine arteries from non-pregnant and pregnant guinea pigs was analyzed immunocytochemically. The NPY content of the uterine artery was, in addition, measured radioimmunologically (RIA). Vasomotor effects of NPY per se and in combination with other vasoconstrictors were examined using a sensitive in vitro method. Pregnancy did not visibly affect density and distribution of NPY immunoreactive fibres. The NPY fibres contained in addition immunoreactivity to dopamine-beta-hydroxylase (marker for noradrenergic neurons). RIA revealed a slight decrease of NPY content during pregnancy, probably due to the increased smooth muscle volume of uterine arteries. The contractile effect of NPY on uterine arteries was weak, while vasoconstriction induced by various agonists was potentiated by NPY, particularly during pregnancy. It is concluded that perivascular NPY-containing nerve fibres may be involved in the dramatic blood flow alterations that occur in the uterine circulation in connection with pregnancy and partus. PMID- 2922493 TI - Comparison of helodermin, VIP and PHI in pancreatic secretion and blood flow in dogs. AB - Helodermin, VIP and PHI, which share a high degree of homology with secretin, have been identified in the gut but their physiological role is unknown. In this study 3 series of tests were carried out to determine the actions of helodermin, VIP and PHI on pancreatic secretion in 6 conscious dogs and amylase release from the dispersed canine pancreatic acini and to correlate the alterations in pancreatic secretory and circulatory effects in 24 anesthetized dogs. Helodermin, VIP and PHI infused i.v. in graded doses (12.5-200 pmol/kg.h) resulted in a dose dependent increase in pancreatic HCO3 secretion reaching, respectively, 100%, 7% and 2% of secretin maximum. When combined with constant dose infusion of CCK-8 (100 pmol/kg.h), helodermin but not VIP or PHI augmented dose-dependently the HCO3 secretion. When added in various concentrations (10(-10)-10(-5)M) to the incubation medium of dispersed pancreatic acini only helodermin but not VIP or PHI increased dose-dependently amylase release reaching about 50% of CCK-8 maximum. In anesthetized dogs, the pancreatic blood flow (PBF) measured by electromagnetic blood flowmetry showed an immediate and dose-dependent increase following the injections of various doses of helodermin, VIP, PHI and secretin, the peak blood flow preceding by about 1 min the peak secretory stimulation. This study shows that helodermin resembles secretin in its potent pancreatic HCO3 stimulation but differs from VIP or PHI which are poor secretagogues but potent vasodilators. We conclude that if tested peptides are released in the gut, helodermin, like secretin, may be involved in the hormonal stimulation of exocrine pancreas, whereas VIP and PHI may serve mainly as vasodilators in the pancreatic circulation. PMID- 2922494 TI - Bombesin microinjected into the dorsal vagal complex inhibits vagally stimulated gastric acid secretion in the rat. AB - Medullary sites of action for bombesin-induced inhibition of gastric acid secretion were investigated in urethane-anesthetized rats with gastric fistula. Unilateral microinjection of bombesin or vehicle into the dorsal vagal complex was performed using a glass micropipet and pressure ejection of 100 nl volume; gastric acid output was measured every 10 min by flushing the stomach. Microinjection of vehicle into the dorsal vagal complex did not alter gastric acid secretion (1.9 +/- mumol/10) from preinjection levels (2.9 +/- 0.8 mumol/10 min). Microinjection of the stable thyrotropin-releasing hormone (TRH) analog, RX 77368, at a 77 pmol dose into the dorsal vagal complex stimulated gastric acid secretion for 100 min with a peak response at 40 min (24.1 +/- 3.2 mumol/10 min). Concomitant microinjection of RX 77368 (77 pmol) with bombesin (0.6-6.2 pmol) into the dorsal vagal complex dose dependently inhibited by 35-86% the gastric acid response to the TRH analog. Bombesin (6.2 pmol) microinjected into the dorsal vagal complex inhibited by 17% pentagastrin infusion-induced stimulation of gastric acid secretion (13.2 +/- 0.8 mumol/10 min) whereas intracisternal injection induced a 69% inhibition of the pentagastrin response. These results demonstrate that the dorsal motor complex is a sensitive site of action for bombesin-induced inhibition of vagally stimulated gastric secretion. However, other medullary sites must be involved in mediating the inhibitory effect of intracisternal bombesin on pentagastrin-stimulated gastric acid secretion. PMID- 2922495 TI - Effects of peptide YY on intestinal blood flow distribution and motility in the dog. AB - Previous investigators in our laboratory have demonstrated that peptide YY (PYY), a putative gut hormone, exerts a potent emetic effect when administered intravenously to conscious dogs. The current study was carried out to examine the effects of an emetic dose of PYY on cardiovascular status, splanchnic blood flow distribution (estimated using 15 micron microspheres) and small intestinal motility in anesthetized dogs. PYY, infused i.v. at a dose of 25 pmol/kg/min led to a localized significant reduction in small intestinal muscularis externa blood flow both 15 and 30 min after the start of PYY infusion in both jejunum and ileum. This decreased muscularis perfusion was not accompanied by any significant change in whole gut wall blood flow and was explained on the basis of an observed significant redistribution of blood flow away from the muscularis towards the mucosa/submucosa. Similar, although non-significant, effects of PYY on colonic blood flow distribution were also observed. Despite the effects on jejunum and ileum, PYY exerted minimal effects on duodenal blood flow. The decrease in ileal and jejunal muscularis blood flows was accompanied by a significant increase in the amplitude of intestinal contractions in these regions. Frequency of contractions was unaltered however. These results demonstrate that PYY infusion leads to concurrent changes in small intestinal blood flow and motility. PMID- 2922496 TI - The cholecystokinin receptor antagonist CR1409 increases plasma cholecystokinin in rats. AB - This study was undertaken to determine whether plasma cholecystokinin (CCK) levels are affected by the administration of the CCK-receptor antagonist CR1409 to rats. Infusion of 0.19, 0.94 and 4.75 mg/kg.h CR1409 for 30 min each into 6 conscious rats increased (P less than 0.05) plasma CCK from 1.3 +/- 0.5 to 6.0 +/ 1.2, 5.4 +/- 1.2, and 5.4 +/- 1.0 pM, respectively. In a subsequent study infusion of stepwise increasing lower doses of 0.3, 1.5, 7.5, 37.5 and 187.5 micrograms/kg.h CR1409 for 30 min each into 6 other rats dose-dependently increased (P less than 0.05) plasma CCK from 1.4 +/- 0.3 to 3.1 +/- 0.6, 4.1 +/- 0.8, 5.4 +/- 1.0, 5.9 +/- 0.8 and 7.1 +/- 1.1 pM, while infusion of saline did not affect plasma CCK concentrations. We therefore conclude that the CCK-receptor antagonist CR1409 increases plasma CCK in the rat. PMID- 2922497 TI - Prevalence of staphylococcal species in four dairy herds. AB - The prevalence of staphylococcal species isolated from bovine mammary glands was determined in four dairy herds. Staphylococcus aureus and S hyicus were the predominant organisms isolated from cows in a herd with a bulk milk somatic cell count (SCC) greater than 900 X 10(3). One herd with a bulk milk SCC of 565 X 10(3) had a high incidence of S aureus while the predominant coagulase-negative species were S epidermidis and S hyicus. S hyicus predominated in two herds with bulk milk SCC less than 200 X 10(3); prevalence of S aureus was low. The impact of herd management practices such as post-milking teat antisepsis on distribution of staphylococcal species is discussed. PMID- 2922498 TI - A strain of Babesia divergens, attenuated after long term culture. AB - The Weybridge strain of Babesia divergens became less virulent after 18 months in culture and was believed to be attenuated. Inoculations with the attenuated line using as many as 5 x 10(8) infected erythrocytes failed to raise a normal infection in Mongolian gerbils (Meriones unguiculatus) whereas, with the line that had been passaged from culture through gerbils at bimonthly intervals, inoculations of 10(7) infected erythrocytes gave rise to fatal infections. Gerbils were immunised with the attenuated line using doses ranging from 5 x 10(5) to 5 x 10(7) infected erythrocytes. Parasitaemias in the infected gerbils did not exceed 0.7 per cent after immunisation. All animals were protected when challenged with the virulent line four weeks later. Control animals died four days after challenge infection. PMID- 2922499 TI - Sensitivity of field isolates of Eimeria species to monensin and lasalocid in the chicken. AB - Isolates of Eimeria species obtained from broiler or from breeder farms were compared for their sensitivity to two ionophorous anticoccidial drugs, monensin and lasalocid. All of 25 isolates from broiler farms were resistant to 100 ppm monensin or 90 ppm lasalocid, while 14 of 16 isolates were resistant to monensin and seven of 16 to lasalocid from breeder farms (replacement layer and broiler breeder). PMID- 2922500 TI - Radiographic measurement from the lateromedial projection of the equine foot with navicular disease. AB - Radiographic measurements from the lateromedial projection of the equine foot were compared in three groups of horses. Group 1 consisted of 143 normal horses, group 2 were 60 horses with clinical navicular disease and group 3 were 161 horses with clinical and radiographic navicular disease. Several measurements tended to be larger in group 3 than group 1. An enlargement of the navicular bone was observed in proximodistal and dorsopalmar directions. Partial enlargement of the pedal bone was observed in groups 2 and 3. Few differences were observed between age classes. All horses aged four years and over had an increased length of the hoof in the dorosopalmar direction and a decrease of the cranial angle of the hoof. Enlargement of the navicular bone fits well into the concept of osteoarthrosis. The pedal bone was partly engaged. These findings may be an expression of a regional acceleratory phenomenon. PMID- 2922501 TI - Development of immunity to incoming radiolabelled larvae in lambs continuously infected with Trichostrongylus vitrinus. AB - Infective third stage larvae (L3) of Trichostrongylus vitrinus were radiolabelled with 75 selenium by a method which did not affect their viability. Three groups of six-month-old lambs were infected daily with 1000 L3 for four, eight and 12 weeks, respectively. After each period, one of those groups (n = 5) and a group (n = 4) of worm-free controls were challenged with three consecutive daily doses of 1000 radiolabelled L3, killed 10 days after the first dose, and their worm burdens examined. After four weeks of continuous infection partial immunity to the establishment of challenge L3 was apparent, and by eight and 12 weeks, with the exception of one sheep, there was almost total resistance to incoming worms. Immunity was also expressed as an inhibition of the development of established worms. PMID- 2922502 TI - Reproduction of proliferative enteritis in gnotobiotic pigs. AB - Gnotobiotic pigs dosed orally with filtrates (0.8 and 0.65 micron) of intestinal mucosa from a pig affected by proliferative haemorrhagic enteropathy developed lesions of proliferative enteritis, affecting mainly the ilea. Other piglets dosed with filtrates of affected mucosa from the same source and from other proliferative haemorrhagic enteropathy or intestinal adenomatosis mucosae, did not develop lesions. All inocula contained numerous campylobacter-like organisms evident in stained smears, Campylobacter coli and C mucosalis. C coli colonised the intestines of all the pigs, C hyointestinalis (which was not detected in the inocula) did so in some affected and unaffected pigs while C mucosalis was not recovered from any of the intestines. Although other explanations are possible the number and viability of the intracellular campylobacter-like forms is likely to be the critical factor in infectivity. In affected intestines the crypts were colonised by campylobacter-like organisms, and their attachment and entry into enterocytes was associated with cellular proliferation. Immunofluorescence reactions suggested that the intracellular campylobacter-like organisms were antigenically distinct from the known Campylobacter species. It is possible, therefore, that porcine proliferative enteritis is caused by a further unidentified Campylobacter species, or that there is a marked antigenic change of C hyointestinalis or C coli on entry into porcine enterocytes. PMID- 2922503 TI - Mouse models for evaluation of virulence of Chlamydia psittaci isolated from ruminants. AB - Intestinal strains of Chlamydia psittaci isolated from faeces of clinically healthy sheep or goats were differentiated from pathogenic strains isolated from animals affected with chlamydial diseases by their virulence in mice. The invasiveness of strains after footpad inoculation was estimated in non-pregnant mice by recording the colonisation and the enlargement of the spleen on days 6 and 9 after inoculation. The abortifacient effect was judged by measuring the colonisation of placenta and fetuses of pregnant mice inoculated intravenously on day 11 +/- 1 of pregnancy. While 25 of 27 pathogenic strains were invasive and able to colonise placenta and fetuses, eight of 10 intestinal strains were not. The model permits graded differentiation between virulent and non-virulent strains and suggests that in propitious circumstances intestinal chlamydia could reach and colonise the placenta and disturb the pregnancy. PMID- 2922504 TI - Comparison of protein patterns between invasive and non-invasive ovine strains of Chlamydia psittaci. AB - Protein patterns displayed in sodium dodecyl sulphate (SDS) electrophoresis by invasive and noninvasive strains of Chlamydia psittaci showed three constant differences, the most distinctive being a band at 90 Kd from invasive strains. In comparison with other methods so far described, this method provides a more efficient means of differentiating between invasive and non-invasive strains. Furthermore, it may lead to the development of improved methods of diagnosis. PMID- 2922505 TI - Work of breathing in exercising ponies. AB - This paper attempts to evaluate the changes in the mechanical work of breathing induced by the increase of ventilation in ponies exercising on a treadmill. Airflow, tidal volume (VT) and oesophageal pressure were simultaneously recorded in eight ponies (four to six years old and weighing 258 +/- 11 kg) before, during and after standardised exercise. Respiratory frequency, VT and minute volume (Ve) for each phase of the experimental protocol were calculated from the collected data. The pressure-volume diagrams were traced and the work per cycle (Wrm) was estimated by measuring the area enclosed in the loop. The work per minute (Wrm) and the work per litre of ventilation (Wrm litre-1) were also calculated. From rest to fast trot Wrm litre-1, Wrm and Wrm had increased 8.1, 13.0 and 55.6 times, respectively. The relationships between Ve and Wrm litre-1 was linear and that between Ve and Wrm curvilinear. Results suggested that the mechanical cost of the work of breathing could be a limiting or at least a constraining factor of the increase of ventilation during strenuous exercise in ponies. PMID- 2922506 TI - Identity of the E-series prostaglandin produced by equine chondrocytes and synovial cells in response to a variety of stimuli. AB - Although an E-series prostaglandin has previously been identified in equine inflammatory exudate, the identity of this eicosanoid as PGE2 has not been confirmed. The objective of this study was the specific characterisation of the prostaglandin produced by equine cells in the presence of an inflammatory stimulus. By using two radioimmunoassays, a relatively non-specific PGE2 assay and a more specific PGE1 assay, it has been possible to identify the E-series prostaglandin produced by equine chondrocytes and synovial cells, in response to a variety of stimuli, as PGE2. PMID- 2922507 TI - Effect of short term intravenous infusion of noradrenaline on energy metabolism in shorn and unshorn pregnant sheep. AB - The effect of a three hour intravenous noradrenaline (NA) infusion, at a dose of 0.8 micrograms min-1 kg-1 bodyweight, on energy metabolism was studied in five pairs of shorn and unshorn pregnant ewes. The concentration of oxygen and carbon dioxide in blood was significantly higher in shorn animals during saline infusion, but this difference between shorn and unshorn groups was removed by NA infusion. Significant increases in the plasma concentrations of glucose, lactate, non-esterified fatty acids (NEFA), 3-hydroxybutyrate and glycerol occurred in both shorn and unshorn animals during NA infusion. There was a 48 per cent larger rise in the plasma NEFA concentration during NA infusion in the unshorn group, suggesting that the lipolytic effect of exogenous NA is greater in these animals. NA infusion had no effect on the plasma concentration of thyroid hormones in both groups of ewes, while growth hormone levels fell and cortisol increased in all animals. The plasma insulin concentration was significantly reduced during NA treatment in the unshorn group, but was unchanged in shorn animals. These results may be a consequence of sympathetic activity already being elevated in shorn ewes due to chronic exposure to an environmental temperature below the thermoneutral zone. PMID- 2922508 TI - Hypotension produced by rapid intravenous administration of chloramphenicol in anaesthetised dogs. AB - Rapid intravenous administration (60 mg s-1) of chloramphenicol (50 mg kg-1) in a 40 per cent w/v polyethylene glycol (400 to 600), 30 per cent ethyl alcohol, 2 per cent benzyl alcohol and 28 per cent distilled water vehicle produced a transient but significant decrease in systemic arterial blood pressure and heart rate with no effect on central venous pressure in sodium pentobarbital anaesthetised dogs. The vehicle alone had no significant effect on any of the parameters studied. Various approaches including the use of anticholinergic, antihistaminergic, antiadrenergic and ganglion blocking drugs failed to attenuate chloramphenicol induced hypotension and bradycardia. However, the hypertensive response to bilateral carotid arterial occlusion was significantly attenuated by rapid intravenous administration of chloramphenicol. The results clearly indicate that chloramphenicol itself, but not its vehicle, is responsible for the severe hypotension and bradycardia. These results also suggest that chloramphenicol induced hypotension and bradycardia might be mediated peripherally via vasodilation due to its direct effect on vascular smooth muscle and centrally via interruption of the baroreceptor reflex pathway. PMID- 2922509 TI - Temporal ELISA response of rams to Brucella ovis following experimental infection or vaccination. AB - Sera from rams vaccinated with antigens extracted chaotropically from Brucella ovis by potassium thiocyanate treatment were used to optimise a whole-cell, enzyme-linked immunosorbent assay (CELISA) and to monitor the temporal serological response of rams which had been challenged with infected semen by the intranasal or intrapreputial route. Three patterns of CELISA response were detected. Thirteen of 15 rams intranasally challenged did not respond serologically (pattern 1 or nil response). Only one of 15 rams in the intranasal group exhibited a rise and fall response with CELISA (pattern 2), while another showed a rise and surge response (pattern 3). The numbers of rams in the intrapreputial group which displayed a pattern 1 or 2 or 3 response were four, nine and two, respectively. No ram with a pattern 2 response excreted B ovis in the semen or showed any other evidence of infection, whereas rams with a pattern 3 response excreted B ovis in the semen and developed palpable lesions. Intrapreputially challenged rams that were CELISA-positive consistently mounted an antibody response against B ovis about two to four weeks earlier than intranasally challenged rams. PMID- 2922510 TI - Enzyme variation and pathogenicity of recent field isolates of Eimeria tenella. AB - Seventy isolates of Eimeria tenella, obtained from commercial poultry farms worldwide and four reference laboratory strains were characterised by studies on the electrophoretic mobility of up to three enzymes. All populations possessed the same electrophoretic form of lactate dehydrogenase and malate dehydrogenase and one of two forms of glucose phosphate isomerase. One isolate was characterised by both forms of glucose phosphate isomerase. Studies on several isolates indicated that there was no correlation between the form of glucose phosphate isomerase found and the pathogenicity of an isolate. PMID- 2922511 TI - Late effects of cancer treatment in children and adults. PMID- 2922512 TI - [The physician as medication. Relationship effects in pharmaceutical medicine as exemplified by the placebo]. AB - The healing effect of relationships within the complex system of medicine was elucidated on the example of the placebo effect. A comparison with an archaic healing system shows that these effects are ubiquitous and are probably valid for all healing systems. The placebo effect occurs not only within sugar pills but is a constant phenomenon with every allopathic drug. Today's research into the endorphin system gives evidence of the psychosomatic pattern of the anodyne effect of placebo. A patients contemporary relationships as well as his culture related self understanding have both an impact on coping mechanisms. In this context the importance of religious belief in coping with illness is emphasised. PMID- 2922513 TI - [Experiences with podophyllotoxin in the treatment of condylomata acuminata]. AB - We treated 26 patients with condylomata acuminata with a 0.5% solution of podophyllotoxin (Condyline). Twelve of these patients were unsuccessfully pretreated with a common podophyllin 20% solution - some of them up to three months. In 22 patients (84.5%) we observed complete healing of lesions within 30 (6 bis 175) days with podophyllotoxin. Prompt response, minor side-effects, and the possibility for the patients to carry out the treatment themselves are the advantages of this podophyllotoxin preparation. PMID- 2922515 TI - [A case from practice (131). Patient: Mr. H.J. S., born 1962, clerk]. PMID- 2922514 TI - [The treatment of severe, therapy-resistant depression using infusions of antidepressants]. AB - Infusion-therapy with antidepressants has been of value in severe as well as therapy resistant depressive states. In addition to doses lower than those used for oral treatment, a more rapid onset of therapeutic effect and a better tolerance, the beneficial effect seems also to depend on the setting in which the treatment takes place. Infusion-therapy is a combined pharmacopsychotherapeutic procedure. Next to infusion-treatment a pretreatment with neuroleptics is advised either via the oral or parenteral route. In extremely refractory depression the infusion-therapy can be applied twice a day; in some cases we resort to continuous infusion for a few days. Infusion-therapy is not applicable in patients prone to epileptic seizures or with serious cerebral dysfunction with a risk of delirium. In case of doubt an EEG is mandatory. Tricyclic antidepressants may not be used in cardiac diseases especially those with troubles of the conduction propagation or repolarization. PMID- 2922516 TI - [Role of electrocardiogram and echocardiogram in the evaluation of hypertensive patients]. PMID- 2922518 TI - [Arterial hypertension in children]. PMID- 2922517 TI - [Radioisotope studies in secondary arterial hypertension]. PMID- 2922519 TI - [Systolic arterial hypertension in the aged]. PMID- 2922520 TI - [Hypertension and strokes]. PMID- 2922521 TI - [Arterial hypertension and pregnancy]. PMID- 2922523 TI - [Voice as an affective index]. PMID- 2922522 TI - [Physical exercise and arterial hypertension]. PMID- 2922524 TI - [10th anniversary of the Center of Family Studies]. PMID- 2922525 TI - [Diagnostic assessment of hypertensive patients]. PMID- 2922526 TI - [Physiopathology of death and resuscitation]. PMID- 2922527 TI - [Coma: a practical approach]. PMID- 2922528 TI - [Family approach to psychosomatic disorders in ambulatory medicine]. PMID- 2922529 TI - [Profile of a psychiatric consultation service for students]. PMID- 2922530 TI - [Phobias]. PMID- 2922531 TI - [Differential diagnosis and treatment of hypogonadism]. PMID- 2922532 TI - [Shock]. PMID- 2922533 TI - [Erythropoietin]. PMID- 2922534 TI - [Aspects of the cycle of Echinococcus multilocularis and of the epidemiology of alveolar echinococcosis in the Jura mountains of Switzerland]. PMID- 2922535 TI - [Current epidemiologic and immunologic aspects of alveolar echinococcosis]. PMID- 2922536 TI - [Immunodiagnosis of alveolar echinococcosis]. PMID- 2922537 TI - [Hepatic alveolar echinococcosis. Clinical and morphologic findings apropos of 80 cases]. PMID- 2922538 TI - [A survey of the practice of psychotherapy by physicians from Vaud (performed in May-June 1987)]. PMID- 2922539 TI - [Infection of the sperm in male sterility]. AB - Sperm infection is a classic cause of infertility. But, it cannot be considered without a minimum of precautions. First, infection of the sperm must be proven (presence of altered leucocytes, even higher than 10(5) or 10(6)/ml is not sufficient). What are the consequences of sperm infection? For many germs, especially chlamydiae and mycoplasma, the effect on sperm is not recognized or demonstrated. Once the infection is recognized, an etiology must be found: unrecognized chronic urethritis, prostatitis and/or chronic vesiculitis, chronic epididymitis. The infection must be adequately treated: according to the germ, according to the results of the resistance to antibiotics, according to the etiology. The author concludes that a true sperm infection is very rare; but it must be looked for as soon as it is suspected, especially in patients with a recent history of genital infection. Therefore an effective treatment of infertility is possible. PMID- 2922540 TI - [Treatment of varicoceles]. AB - The mechanisms of infertility in varicoceles are still ill-defined; their repercussions are variable and unrelated to the degree of venous dilatations (a good number of such patients have no fertility problems). Oligo-astheno teratospermia is a non-pathognomonic entity, also encountered in chronic infections, previous history of cryptorchidism, gonadotrophic insufficiencies and toxic of iatrogenic causes. Should varicoceles be operated on, in order to treat the oligo-astheno-teratospermia? After strongly advocating surgery in the 60's, this approach is, in retrospect, being questioned. Varicoceles affect a very heterogeneous population with various degrees of infertility. To answer this question, randomized studies based on strict criteria, should be undertaken. PMID- 2922541 TI - [Male infertility and intrauterine insemination with abnormal sperm]. AB - Intra-uterine insemination of capacitated sperm has disappointing results when this sperm is abnormal, since the overall pregnancy rate does not exceed 11 p. cent of the couples who have not given up before the 6th cycle of treatment. However, considering the ineffectiveness of the treatments of idiopathic or secondary oligo-astheno-teratospermia, and the still limited effectiveness of fertilization in vitro with his type of sperm, intra-uterine CAI may currently be offered for a limited time to sterile couples with very abnormal sperm, contingent on a precise methodology in the preparation of the sperm as well as the time of ovulation. PMID- 2922542 TI - [The male factor in fertilization in vitro]. AB - Every sperm parameter has an effect on the chances of fertilization. When fertilization has been obtained with a sperm, the cleavage rate is identical regardless of the count, the mobility or the results of the migration test. On the contrary, in case of teratospermia, the cleavage rate of fertilizing sperms is significantly decreased. The rate of pregnancy by transfer is identical with normal sperm and sperm deficiency. PMID- 2922543 TI - [When should donor artificial insemination be considered?]. AB - DAI (artificial insemination with donor) is a method used in male infertility. If azoospermia represents the standard medical indication of DAI, moderate sperm insufficiencies may, on the contrary, benefit from other medically assisted procreation techniques. The place of artificial insemination with spouse or fertilization in vitro as opposed to DAI, is discussed in the presence of male hypofertility. The DAI must be used as a last resort after failure of all other treatments. PMID- 2922544 TI - [Sterility and sexuality]. AB - In some couples, an absence of pregnancy may be related to sexual difficulties. They should always be considered if the couples do not mention this subject. It is also necessary to keep in mind that sterility may result in sexual problems. In all cases, it is the physician's responsibility to listen to, reassure and comfort the couples who look to him/her for the realisation of their dream: having a child. PMID- 2922545 TI - [Interpretation of the sperm count]. AB - The sperm count has proved to be one of the first examination performed in evaluating the fertility of a couple. It has been possible to establish a few standardized norms from the sperm count of fertile men, but, except for azoospermia, there is no specific limit beyond which it is possible to confirm the absence of fertilization of a sperm. The various criteria of the sperm count then examined, emphasizing the importance of studying the morphology, on optical as well as electron microscopy, since it is the spermatozoid's morphology as well as their mobility that differentiate fertile man from infertile ones. Any abnormality often severely compromises the ability to fertilize spermatozoids. PMID- 2922547 TI - [Substance abuse: social aspects]. PMID- 2922546 TI - [Testing the fertility of the spermatozoa]. AB - The sperm count, an absolutely necessary examination, seems no longer sufficient to establish a prognosis of fertility. Fertilization in vitro, for a diagnostic purpose, would be the ideal examination, but because of the ethical and technical problems it raises, other tests have been developed. The test of spermatozoid survival at 24 hours in Menezzo's B2 medium and interspecific fertilization in vitro (hamster-test) are carried out on isolated spermatozoids according the FIV protocol. The survival test provides two parameters: the presence of mobility and the rate of retention of the mobility after 24 hours. With the hamster-test it is possible to study the penetration and decondensation of the spermatozoids in the ovocytes. The results obtained with the survival test show that the absence of gradual mobility and a retention rate below 25 p. cent after 24 hours, significantly affect the cleavage of ovocytes during FIV. These two parameters affect, in a similar fashion, the percentage of fertilized ovocytes in the hamster-test. The latter seems less specific than the survival test to establish a prognosis before FIV. However, it is interesting as it allows the study of the different stages of fertilization of spermatozoid samples, from the same ejaculation, under varied experimental conditions. These tests require a standardization and present a definite advantage during exploration prior to FIV, AIC. PMID- 2922548 TI - [Substance abuse: individual aspects]. PMID- 2922549 TI - [Substance abuse: afterwards]. PMID- 2922550 TI - [At Pierre-Nicole]. PMID- 2922551 TI - [Understanding wound healing in order to treat a wound better]. PMID- 2922552 TI - [Radiotherapy: problems and sequelae, treatment measures]. PMID- 2922553 TI - [Nutrition of patients in radiotherapy]. PMID- 2922554 TI - [Practical aspects of bladder catheterization]. PMID- 2922555 TI - [Making good use of culture in nursing care]. PMID- 2922556 TI - [General care, psychiatry--towards a common education]. PMID- 2922557 TI - [The views of others are sometimes disturbing]. PMID- 2922558 TI - [Occupational nurses: still an ambiguous function]. PMID- 2922559 TI - [Detection of deafness in children]. PMID- 2922560 TI - [Planned hemodilution in orthopedics]. PMID- 2922561 TI - [New ways to explore the spine]. PMID- 2922562 TI - [Cardioversion after a loading dose of amiodarone]. PMID- 2922563 TI - [Risks and benefits of treatment with sodium fluoride of osteoporosis with vertebral collapse]. PMID- 2922564 TI - [Common pulmonary tuberculosis]. PMID- 2922565 TI - [Standard thoracic radiography in children. Diagnosis orientation and management]. PMID- 2922566 TI - [Non-steroidal inflammatory agents]. PMID- 2922567 TI - [Thrombolytic agents]. PMID- 2922568 TI - [Acute angle-closure glaucoma. Etiology, physiopathology, diagnosis, course and prognosis, treatment]. PMID- 2922569 TI - [Depressive syndrome. Etiology (including iatrogenic), diagnosis, course and prognosis, treatment]. PMID- 2922570 TI - The relation between cutaneous blood flow and cell content in the tuberculin reaction. AB - The relationship of velocity of blood flow to density and microanatomical distribution of inflammatory cells in the dermis was studied in 20 human tuberculin tests. Most positive reactions showed maximal blood flow velocities (measured as red blood cell (RBC) flux) at the centre of the reaction, but the two most intense responses showed 'central relative slowing' (CRS) with higher RBC flux at the periphery. Two of the four clinically negative reactions showed a considerable acceleration of blood flow, but the other two showed no such acceleration. The packing density of lymphocytes/monocytes in the perivascular zone was greater in the stronger positives than in the weaker reactions. The density of cells in the intervening dermis was markedly lower than in the foci: the lesions with CRS had the highest density of cells in the diffuse infiltrate of the reticular dermis. At the centre of the reaction, blood flow velocity was generally related to density of cellular infiltrate, except in those with CRS, which had a disproportionately lower blood flow velocity. The finding that the circulatory adaptation to a delayed hypersensitivity reaction can be inadequate may explain the dermal acidosis previously observed in intense skin test reactions, and may be the underlying mechanism of necrosis in hypersensitivity reactions. PMID- 2922571 TI - Recombinant protein A of non-staphylococcal origin is not mitogenic for human peripheral lymphocytes. Mitogenicity of natural protein A is caused by a contaminant. AB - Recombinant protein A(SpA) produced in Escherichia coli or Bacillus subtilis bacteria did not induce activation of human peripheral mononuclear cells, whereas SpA preparations obtained from naturally occurring Staphylococcus aureus bacteria as well as recombinant SpA from Staphylococcus xylosus were potent mitogens. Further purification of SpA from S. aureus showed that the mitogenic material was concentrated in the side fractions containing more basic molecules. Some staphylococcal enterotoxins are mitogenic for human cells and in order to test whether contaminating enterotoxins would be responsible for the mitogenic effect of SpA preparations, rabbit antibodies were produced against enterotoxin A and B. These antibodies inhibited activation of human cells induced by the enterotoxins used for immunization but did not affect the activation induced by SpA preparation. The addition of selected human sera to in vitro cultures resulted in an inhibition of the response induced by low doses of SpA. There was no clear relationship between these effects and the content of IgG antibodies against staphylococcal enterotoxins A, B, and Cl in the sera. Thus, we conclude that the mitogenicity of SpA preparations is caused by contaminating molecules, probably not enterotoxins A, B, or Cl. PMID- 2922572 TI - Production of human antibodies to bee venom phospholipase A2 in vitro. AB - Phospholipase A2 (PLA) is the major antigen of bee venom. Whereas individuals frequently stung by bees, such as bee keepers, show high levels of IgG4 anti-PLA antibodies in serum, most patients sensitive to bee venom possess increased IgE anti-PLA. We have established a culture system by which anti-PLA antibodies can be induced in vitro. Peripheral blood mononuclear cells were stimulated in a first step with PLA and/or pokeweed mitogen (PWM). After 3 days of culture the cells were washed and further incubated with fresh medium. Anti-PLA antibodies were estimated by an enzyme-linked immunosorbent assay (ELISA) and anti-PLA antibody secreting cells were counted by means of an ELISA plaque assay. Cells from bee keepers, but not those from normal donors, produced anti-PLA IgG in vitro. The isotype pattern of anti-PLA antibodies produced in vitro was identical to that found in serum of the respective donor. Anti-PLA IgM antibody-secreting cells developed at low frequencies in both bee keepers and normal donors whereas PLA-specific IgE could not be detected. The formation of anti-PLA IgG was suppressed by high amounts of antigen, while the IgM response was not affected. We conclude that PWM-induced antibodies reflect the in vivo situation of the donors and that anti-PLA IgG and IgM are regulated by different pathways and mechanisms. PMID- 2922573 TI - IgG subclasses of pneumococcal antibodies--effect of allotype G2m(n). AB - Antibody responses to three pneumococcal polysaccharides (types 3, 14, and 18C) were analysed after vaccination with a 23-valent polysaccharide vaccine. Antibodies to all three polysaccharides could be detected before immunization. Clear cut IgG, IgA, and/or IgM antibody responses to the polysaccharides were seen in three-quarters of the vaccinees. IgG2 was the predominant and IgG1 the second most abundant subclass of anti-pneumococcal IgG antibodies both before and after the vaccination. The relative proportions of IgG2 and IgG1 antibodies exhibited a continuous variation from 1:0 to approximately 0:2. After vaccination, G2m(n)-positive homozygotes had about four times more IgG2 antibodies (anti-14 and anti-18C) than G2m(n)-negative vaccinees. Heterozygotes occupied an intermediate position. The same pattern was seen less clearly in type 3 antibodies after vaccination, and in all three antibodies before vaccination. The G2m(n) allotypes had no detectable effect on the levels of IgG1, IgG4, or IgM antibodies, and possibly a weak effect on IgG3 and IgA antibodies (G2m(n) positive homozygotes responded strongly). PMID- 2922574 TI - Liver sinusoidal blood containing natural killer-like cells. AB - Rat liver sinusoidal washout cells were examined. These cells, which are marginated in sinusoids, could be washed out by simple flushing of the vasculature with culture media without enzymes and under physiological portal pressure. They revealed, in comparison to peripheral blood mononuclear cells, high cytotoxic activity commonly attributed to the natural killer (NK) and natural cytotoxic (NC) cells, and were found to be anti-asialo-GM1-negative. Liver sinusoidal cytotoxic cell (LSCC) activity has been found to be associated with the large granular lymphocytes in low-density cells in OX8-positive as well as in OX8-negative populations. The mononuclear cells washed out from the liver microvasculature could be stimulated with NK-sensitive targets to release soluble factors which selectively lyse YAC-1 tumour cells and inhibit growth of normal haematopoietic granulocyte-macrophage colony-forming cells in vitro. The cytotoxic cell population in the liver turned out to be blood-borne in origin and not resident. Our findings suggest that liver sinusoidal cytotoxic cells represent an NK population with a predilection for marginating in the liver and may be important in eliminating tumour or virus infected cells passing through the liver from the circulation. The mechanism of their accumulation in liver sinusoids remains unclear. PMID- 2922575 TI - Urethral recurrence after cystoprostatectomy for bladder carcinoma. AB - Eighty-nine male patients underwent cystoprostatectomy for bladder carcinoma. Prophylactic urethrectomy was performed only on 7 patients whose tumour extended to or beyond the bladder neck. During the follow-up period 9 of 82 patients (11%) developed a urethral recurrence. Eight out of these 9 patients had carcinoma in situ or multiple papillary tumours in the bladder. Of all those patients who had carcinoma in situ, either primary or concomitant with papillary tumour, 18% developed urethral recurrence. The corresponding figure for patients with multiple tumours in the bladder was 15%. Thus the presence of carcinoma in situ or multiple tumours in the bladder seem to be important risk factors for urethral recurrence after cystoprostatectomy. PMID- 2922576 TI - Urodynamics in radical retropubic prostatectomy. AB - Urodynamic examinations were performed on 19 patients undergoing radical retropubic prostatectomy for localized prostatic carcinoma. Altogether 16 urodynamic parameters were analyzed preoperatively and 6 months afterwards. There was a significant decrease in bladder wall compliance and an increase in intravesical and abdominal pressure at maximum flow rate postoperatively. These findings may reflect a partial bladder decentralization caused by surgery. The amount of residual urine was reduced postoperatively. Two patients (10.5%) were totally incontinent, and in both the postoperative urethral closure pressures were low. PMID- 2922577 TI - Pyeloureteral dynamics. Pelvic pressure and kidney function in partial long-term ureteric obstruction. AB - In 10 pigs with reno-scintigraphically proven normal upper urinary tracts, a standardized partial obstruction of the left ureter was created at the lower kidney pole level. Three weeks later kidney function was scintigraphically reassessed and the pressure flow relationship in the flow range 0-20 ml/min outlined. The partially obstructed pelvic baseline pressure varied from 9.0 to 32.0 cmH2O. During perfusion small increases in pelvic pressure were seen at all flow rates in the individual cases and there was a linear relationship between pressure and flow. Compared to previous results of a similar but acute obstruction the results were identical in pressure ranges and pressure flow profile. This demonstrates, that a longitudinal stability in transport mechanism qualities is present also during the course of obstruction. The pelvic pressure at low flow rates was significantly correlated to kidney function depression, whereas perfusion pressures at high flow rates did not show any correlation, except at 20 ml/min. This clearly indicates, that the pelvic pressure at normal urine flow rate is an important factor in the pathogenesis of obstructive nephropathy. PMID- 2922578 TI - Cystic dilatation of Cowper's gland duct--an overlooked cause of urethral symptoms? AB - Dilatation of Cowper's gland duct was diagnosed in four men with symptoms including post-voiding dribbling, frequency of micturition, dysuria and hematuria. Cystourethrography gave the correct diagnosis in all cases. Treatment consisted of transurethral incision of the cystic excretory duct, providing marsupialization into the urethra. Investigation of longstanding or recurrent episodes of urethral symptoms in men should include cystourethrography with this lesion in mind. It seems to be less rare than was previously assumed. PMID- 2922579 TI - IGA nephropathy: a retrospective evaluation of prognostic indices in 176 patients. AB - One hundred and seventy-six patients with mesangial IgA nephropathy have been studied retrospectively. Mean follow up from apparent onset of the disease was 9.3 years and with follow up from the diagnostic renal biopsy of 4.6 years. Our aim was to evaluate the prognostic significance of sex, age and type of symptoms at onset. The degree of proteinuria, presence of hypertension or decreased renal function, histological lesions and IFL pattern at the time of the diagnostic renal biopsy were recorded. 17 of the patients developed End Stage Renal Failure (ESRF) during the study. According to the Logrank test (renal survival) and Cox stepwise proportional hazard model, severity of glomerular mesangial lesions and degree of proteinuria are the most important indicators of a poor prognosis. The significance of all other parameters disappear after correction for histological lesions and degree of proteinuria. Our conclusion is that a semiquantitative light microscopical examination is an excellent prognostic index in IgA nephropathy, as is a simple determination of protein excretion in the urine. PMID- 2922581 TI - Extracorporeal shock wave lithotripsy: first choice therapy for ureteral stones. AB - Extracorporeal shock wave lithotripsy represents the first choice therapy for reno-ureteral stone disease, being successful in more than 85% of cases. When extracorporeal shock wave lithotripsy is associated with both appropriate cystoscopic manipulations and with a proper positioning of the patient on the stretcher of the lithotripter, it can be successfully applied to ureteral stones regardless of their specific location. We report 99 patients with ureteral calculi submitted to extracorporeal shock wave lithotripsy with a stone free rate of 98%. PMID- 2922580 TI - Intestinal oxalate and calcium absorption in recurrent renal stone formers and healthy subjects. AB - The fractional intestinal absorption of oxalate and calcium was investigated by isotope techniques in 20 normal subjects and in 12 idiopathic calcium oxalate stone formers. The greatest amount of 14C-oxalate was excreted during the first six hour period in controls as well as in stone formers. The stone formers had a greater intestinal uptake of oxalate (11 +/- 5.1%) than the controls (6.2 +/- 3.7%; p less than 0.01). There was no significant relationship between the fractional absorption of oxalate and the total urinary oxalate excretion. The stone formers also had a higher fractional uptake of calcium compared to the controls (55 +/- 11% vs. 47 +/- 9.1%; p less than 0.05). There was a positive relationship (r = 0.47) between the urinary excretions of calcium and oxalate in the stone formers. During these conditions no correlation could be demonstrated between the fractional absorptions of oxalate and calcium, neither in the stone formers nor in the controls. In conclusion, patients with recurrent formation of calcium oxalate containing stones appear to have an enhanced intestinal uptake of both oxalate and calcium. This disturbance could be of primary pathogenic importance for their stone forming propensity. PMID- 2922582 TI - Transvaginal-distal urethroplasty. A multipurpose operation. AB - Experience of a surgical procedure used to treat five women with varying pathology of the lower urinary tract is described. Transvaginal elongation of the urethra and distal urethroplasty were performed in all cases, with gratifying results. The procedure is presented as a multipurpose operation. PMID- 2922583 TI - Nephrogenic adenoma. Reports of two cases. AB - Nephrogenic adenoma is a rare lesion of the urinary tract. Two cases in the urinary bladder are described. Histologically the tumor consists of cystic and tubular structures resembling the distal part of the nephron. The etiology and pathogenesis are discussed and a new etiologic theory is presented. PMID- 2922584 TI - Cancer incidence of workers in a Finnish sawmill. AB - The cancer incidence of 1,223 sawmill workers with continuous employment of at least one year between 1 January 1945 and 31 December 1961 was followed until 31 December 1980. Separate analyses were made for the 801 workers hired after 1 January 1945, and smoking habits were surveyed. Among the men, 90 cases of primary cancer were detected versus 83.5 expected and among the women 55 cancer cases versus 44.5 expected. Skin cancer was in excess among the men, especially among those employed after 1 January 1945. Lip, mouth, and pharynx cancer and lymphomas were also slightly in excess among the men, as was leukemia among both sexes. Workplace exposure, especially to chlorophenols, may be associated with the excess skin cancer and the slight excess of lymphomas, but this finding should be further evaluated with special emphasis on well-defined exposure data. PMID- 2922586 TI - Risk of lung, larynx, pharynx and buccal cavity cancers among carbon electrode manufacturing workers. AB - Among workers employed in factories producing carbon graphite products the risk of cancer due to exposure to polycyclic aromatic hydrocarbons was estimated. In one cohort (plant A), a cancer incidence study was carried out; the number of cases were not significantly increased for lung cancers [7 cases, standardized incidence ratio (SIR) 79] or for cancers of the upper respiratory and alimentary tract (10 cases, SIR 103). In another cohort (plant B), a mortality study was carried out; neither the mortality from lung cancer [13 deaths, standardized mortality ratio (SMR) 118] nor that from upper respiratory and alimentary tract cancers (10 deaths, SMR 125) was significantly higher than expected. Within each cohort, a case-referent study was carried out. In plant A the odds ratios were high but nonsignificant for lung cancers (odds ratio 3.42) and upper respiratory and alimentary tract cancers (odds ratio 2.19) and they showed a nonsignificant relationship with duration of exposure. In plant B, the odds ratios were low for every cancer site. PMID- 2922585 TI - Cancer risks among New Zealand meat workers. AB - The study reports a series of case-referent studies based on the New Zealand Cancer Register and involving 19,904 male cancer patients aged 20 years or more at the time of registration during the period 1980-1984. For each cancer site, the registrations for the remaining sites formed the reference group. An increased risk for lung (OR 1.30, 95% CI 1.06-1.58) and laryngeal (OR 2.01, 95% CI 1.19-3.39) cancer was found among meatworkers. It was confined to men aged less than 65 years at registration. The risk for soft-tissue sarcoma was elevated (OR 1.90, 95% CI 0.90-4.02). The risk estimate for all types of leukemia was elevated moderately (OR 1.45, 95% CI 0.90-2.31), but cell type-specific analyses revealed a greater effect for acute myeloid leukemia (OR 2.12, 95% CI 1.09-4.12). This study adds to the evidence that employment as a meatworker is associated with increased risk for several forms of cancer. PMID- 2922587 TI - Lung cancer, smoking, and employment in foundries. AB - A case-referent study on lung cancer was conducted in Cracow, Poland. Men dying of lung cancer within a 6-year period (1980-1985) formed the case group. The reference series was selected from death registers and was frequency-matched with the cases by sex and age. Deaths due to other respiratory diseases were excluded. Information on the occupation, smoking habits, and residency of 901 cases and 875 referents was collected from their next-of-kin. The combined effect of smoking and industrial exposure, in particular employment in steel or iron foundries, was investigated by multivariate analyses and was very well fitted by a multiplicative model. Foundry employment, in particular in the younger age (less than 70 years) group, occupational exposure to known carcinogens in other industries for more than 20 years, and smoking were found to be risk factors. PMID- 2922588 TI - Mortality of auto mechanics. A ten-year follow-up. AB - This study was set up to investigate whether work in car repair workshops is associated with an increased risk of ischemic heart disease and specific malignant neoplasms. For this purpose, a cohort of auto mechanics has been followed through 10 years with regard to cause-specific mortality. Comparisons were made with another cohort of skilled male workers who were not exposed to asbestos or petrochemical substances. The auto mechanics' mortality was increased for ischemic heart disease [standardized mortality ratio (SMR) 121, 95% confidence interval (95% CI) 102-145], other cardiovascular diseases (SMR 112, 95% CI 82-150), cancer (SMR 115, 95% CI 97-136), other diseases (SMR 119, 95% CI 94-149), and external causes (SMR 131, 95% CI 113-153). For specific cancer sites, increases were seen for pancreatic cancer, urinary cancer outside the bladder, and pleural mesothelioma. PMID- 2922589 TI - Triazine herbicides and ovarian epithelial neoplasms. AB - The possible role of a class of herbicides, triazines, in ovarian carcinogenesis has been evaluated in a population-based case-referent study. The trade names reported by the study subjects, and the type of cultivation in which they worked, were used for the assessment of exposure. Women previously exposed to triazines showed a significant relative risk of 2.7 for ovarian neoplasms. Although none of the doses could be quantified for the study subjects, two risk trends in favor of the plausibility of the association were found: the first by duration and the second by probability of exposure. The population representativity of the study and the comparability of information between the cases and referents suggest the lack of any major bias in the results. Triazine-related risk remained consistent when the analysis was restricted to farmers and when the exposure to other herbicides and to other types of cultivation were considered. Unexposed farmers had the same risk as unexposed nonfarmers. PMID- 2922590 TI - Olfactory function in painters exposed to organic solvents. AB - The olfactory receptor cells are in direct contact with the exterior environment, and some chemical agents can impair olfactory function. The olfactory function of 54 painters exposed to organic solvents was compared with that of 42 unexposed referents. A new clinical test validated for the sense of smell was used, the University of Pennsylvania Smell Identification Test. Age, smoking habits, exposure to organic solvents, and medical disorders of importance for the sense of smell were recorded. The painters had a somewhat lower test score than the referents. However, the influence of the exposure variable was not statistically significant in a multiple regression analysis including age and smoking habits. The exposure to organic solvents was low, and therefore an effect of high exposure on olfactory function cannot be ruled out. Since some of the painters had earlier been highly exposed, the effects of high exposure are likely to be reversible. PMID- 2922591 TI - Subjective symptoms and psychological performance of chlorine-alkali workers. AB - Subjective symptoms and psychological performances on a computer-administered test battery were studied among a group of 60 chlorine-alkali workers and their matched referents. The exposure time of the group exposed to inorganic mercury vapor had been about 14 years, and the estimated long-term average exposure had been about 25 micrograms/m3 of air. The exposed workers had an actual mercury concentration of 51.9 (SD 25.0, range 15-150) nmol/l in blood and 84.1 (SD 56.6, range 15-260) nmol/l in urine. Neither perceptual motor nor memory nor learning abilities of the mercury-exposed workers showed any disturbances in a comparison with the referents. However, the exposed group reported statistically significantly more memory disturbances than the referents. Strain caused by three shift work was a possible cofactor for other increased subjective symptoms, namely, for sleep disorders, fatigue, and confusion. PMID- 2922593 TI - Europe tries to untangle laws on patenting life. PMID- 2922592 TI - Self-reported symptoms in the neck and upper limbs of female assembly workers. Impact of length of employment, work pace, and selection. AB - In a questionnaire study 148 women in assembly work reported statistically significantly higher rates of pain, in the last 7 d, in their shoulders (odds ratio 3.4) and hands (odds ratio 2.8) as compared to 60 referents age-adjusted. There was a strong association between duration of employment and complaints in the hands. For the younger women, but not the older ones, there was an increase in pain in the shoulders, neck, and upper back with duration of employment. The odds ratio for pain in the shoulders and neck increased with an increasing work pace, except for very high paces, for which there was a decrease. Among 76 former assembly workers 26% reported pain as the cause of having left this work. There was no overall increase in the frequency of complaints among those who had left. PMID- 2922594 TI - No patent for Harvard's mouse. PMID- 2922595 TI - Specific recognition of cruciform DNA by nuclear protein HMG1. AB - Cruciform DNA, a non-double helix form of DNA, can be generated as an intermediate in genetic recombination as well as from palindromic sequences under the effect of supercoiling. Eukaryotic cells are equipped with a DNA-binding protein that selectively recognizes cruciform DNA. Biochemical and immunological data showed that this protein is HMG1, an evolutionarily conserved, essential, and abundant component of the nucleus. The interaction with a ubiquitous protein points to a critical role for cruciform DNA conformations. PMID- 2922596 TI - Reciprocal effects of hyper- and hypoactivity mutations in the Drosophila pattern gene torso. AB - In Drosophila, five "terminal" polarity genes must be active in females in order for them to produce embryos with normal anterior and posterior ends. Hypoactivity mutations in one such gene, torso, result in the loss of the most posterior domain of fushi tarazu expression and the terminal cuticular structures. In contrast, a torso hyperactivity mutation causes the loss of central fushi tarazu expression and central cuticular structures. Cytoplasmic leakage, transplantation, and temperature-shift experiments suggest that the latter effect is caused by abnormal persistence of the torso product in the central region of the embryo during early development. Thus, the amount and timing of torso activity is key to distinguishing the central and terminal regions of the embryo. Mutations in the tailless terminal gene act as dominant maternal suppressors of the hyperactive torso allele, indicating that the torso product acts through, or in concert with, the tailless product. PMID- 2922598 TI - Financial benefit from research. PMID- 2922597 TI - Fenfluramine studies. PMID- 2922599 TI - Duesberg's PNAS paper. PMID- 2922600 TI - Animal research and government policy. AB - In the report "Synthetic CD4 peptide derivatives that inhibit HIV infection and cytopathicity" by Jeffrey D. Lifson et al. (5 Aug., p. 712), the last seven residues of the CD4 peptide (26-50) should have been SFLTKGP rather than STLTKGP. PMID- 2922601 TI - Animal rightists claim bomb blast. PMID- 2922602 TI - Ethical questions haunt new genetic technologies. PMID- 2922603 TI - NIH offers AZT to exposed workers. PMID- 2922604 TI - Ecologists wary about environmental releases. PMID- 2922605 TI - New family of adhesion proteins discovered. PMID- 2922606 TI - Sequence-specific peptide cleavage catalyzed by an antibody. AB - Monoclonal antibodies have been induced that are capable of catalyzing specific hydrolysis of the Gly-Phe bond of peptide substrates at neutral pH with a metal complex cofactor. The antibodies were produced by immunizing with a Co(III) triethylenetetramine (trien)-peptide hapten. These antibodies as a group are capable of binding trien complexes of not only Co(III) but also of numerous other metals. Six peptides were examined as possible substrates with the antibodies and various metal complexes. Two of these peptides were cleaved by several of the antibodies. One antibody was studied in detail, and cleavage was observed for the substrates with the trien complexes of Zn(II), Ga(III), Fe(III), In(III), Cu(II), Ni(II), Lu(III), Mg(II), or Mn(II) as cofactors. A turnover number of 6 x 10(-4) per second was observed for these substrates. These results demonstrate the feasibility of the use of cofactor-assisted catalysis in an antibody binding site to accomplish difficult chemical transformations. PMID- 2922608 TI - Animal rights and animal wrongs. PMID- 2922607 TI - Sindbis virus: an efficient, broad host range vector for gene expression in animal cells. AB - Sindbis virus, an enveloped virus with a single-stranded RNA genome, was engineered to express a bacterial protein, chloramphenicol acetyltransferase (CAT), in cultured insect, avian, and mammalian cells. The vectors were self replicating and gene expression was efficient and rapid; up to 10(8) CAT polypeptides were produced per infected cell in 16 to 20 hours. CAT expression could be made temperature-sensitive by means of a derivative that incorporated a temperature-sensitive mutation in viral RNA synthesis. Vector genomic RNAs were packaged into infectious particles when Sindbis helper virus was used to supply virion structural proteins. The vector RNAs were stable to at least seven cycles of infection. The expression of CAT increased about 10(3)-fold, despite a 10(15) fold dilution during the passaging. Sindbis virus vectors should prove useful for expressing large quantities of gene products in a variety of animal cells. PMID- 2922609 TI - Epidemiologic investigation. PMID- 2922610 TI - Pesticides and kids. PMID- 2922611 TI - NAS weighs in with 7-lb diet guide. PMID- 2922612 TI - GM, Hughes settle stock fight. PMID- 2922613 TI - France introduces bioethics law. PMID- 2922614 TI - Free calcium at rest during "catch" in single smooth muscle cells. AB - Tension and intracellular free calcium concentration [( Ca2+]i) were measured simultaneously in single smooth muscle cells isolated from the anterior byssus retractor muscle (ABRM) of Mytilus edulis that were loaded with the fluorescent Ca2+ indicator fura-2. Electrical stimulation evoked a transient elevation of [Ca2+]i associated with a "catch" contraction. During the catch state, however, [Ca2+]i was effectively at its resting level and was unaffected by 5 hydroxytryptamine, which induced a rapid relaxation from catch. The results indicate that a maintained high [Ca2+]i is not required for the maintenance of catch tension in intact ABRM and that there was no significant change in [Ca2+]i upon abolition of catch. PMID- 2922615 TI - Guide to biotechnology products and instruments. Guide to scientific instruments. PMID- 2922616 TI - The biology of heme II. PMID- 2922617 TI - Growing up together. PMID- 2922618 TI - Reporting of child abuse: influence of characteristics of physician, practice, and community. AB - This survey of 120 Alabama pediatricians, family physicians, and general practitioners investigated the relationship between physician, practice, and community characteristics and the factors that impede reporting of detected child abuse. Solo practitioners and rural physicians were most concerned about the effect of reporting on their relationship with their patients. Small town physicians, recent medical school graduates, and physicians who had attended child abuse workshops were most likely, and urban physicians least likely, to endorse an ethical or legal responsibility to report. Attendees of workshops were more confident in their ability to recognize abuse and less likely to think they could best handle the case themselves. Male physicians were reluctant to report because of the likelihood of having to appear in court. All physicians were reluctant to report cases about which they were uncertain and were concerned about the lack of prompt action after their reports; general practitioners expressed reluctance to report due to a wide variety of factors. PMID- 2922619 TI - Large pericardial effusion after cardiac surgery: role of echocardiography in diagnosis and management. AB - We performed M-mode and two-dimensional (2-D) echocardiograms prospectively in 140 patients an average of eight days after open heart surgery. Large pericardial effusions occurred in 13 patients; three had complete circumcardiac pericardial effusion, four had local anterior adhesions, five had extensive anterior adhesions (posterior loculated effusion), and one had a large loculated pericardial effusion contiguous to the right atrium. In five patients with tamponade, the effusion was drained, with immediate reversal of symptoms and signs of tamponade. In the other eight patients, who had no deterioration in cardiovascular status, the effusion was not drained; instead, these patients were treated medically with indomethacin and observed with serial echocardiograms, and the effusions eventually disappeared. The most consistent echocardiographic differences between the five patients with and the eight patients without tamponade were that patients with tamponade had larger posterior pericardial effusions, more severe left atrial compression, and more indentation of the right atrial wall. Echocardiography plays an essential role in diagnosis and management of large pericardial effusions after open heart surgery. Patients with large pericardial effusions who are clinically stable need only medical management, including serial echocardiograms, but drainage is indicated if the cardiovascular or respiratory status worsens. Certain echocardiographic findings indicate a high probability of tamponade. PMID- 2922620 TI - Preoperative cardiac consultations in a teaching hospital. AB - Perioperative consultations may play a major role in the care of surgical patients in an era of prospective payments. Since insurance reimbursement policy favors limitations in the number of consultants on a case, general medicine ("holistic") consultation services may become preferred perioperative consultants in the future. To focus curriculum planning for perioperative consultants, we reviewed the content of 60 consecutive perioperative consultations by noncardiac surgery services to a university cardiology consultation team. Clinical descriptions of the patients' exercise tolerance showed that 95% of the patients belonged in functional classes I and II. One fourth of the requests were for routine preoperative clearance. The most frequent cardiac conditions for evaluation were congestive heart failure, old myocardial infarctions, murmurs, abnormal electrocardiograms, angina, and previous histories of coronary artery bypass surgery. Few patients needed management of arrhythmias. Physicians involved in perioperative care should assess their abilities in managing these cardiac conditions. PMID- 2922621 TI - Hypertension: variations in prevalence in the black population. AB - Prevalence trends in hypertension in black men and women show an inversion at about ages 45 to 54 years. Incidence, mortality, and treatment of hypertension after age 35 can probably be related to this inversion. Incidence data are inconsistent and scanty. Morbidity data are incomplete and mostly unreliable. Mortality data partially explain the inversion. Long-term epidemiologic studies of hypertension in black elderly persons are needed to explain these variations in prevalence, which may have a beneficial impact on treatment and prognosis. PMID- 2922622 TI - Biochemical testing in patients with alcoholic liver disease. AB - We evaluated physicians' laboratory utilization patterns for hospitalized patients with alcoholic liver disease and examined the relationship between the frequency of test ordering and certain variables in clinical outcome. During the study, 185 patients with alcoholic liver disease were hospitalized 378 times at the VA Medical Center, Long Beach, California. Physicians ordered liver panels (including serum albumin, alkaline phosphatase, total bilirubin, lactic dehydrogenase, glutamic pyruvate transaminase, and glutamic oxaloacetic transaminase) an average of 7.4 times per hospitalization. Increased biochemical testing did not decrease length of stay or improve clinical outcomes such as development of complications or survival of hospitalization. Since the treatment of alcoholic liver disease is largely supportive and not dependent upon frequent biochemical testing, we recommend that these tests be ordered only when patients are admitted to or discharged from the hospital, and when there has been a clinical change. PMID- 2922623 TI - Carcinoma of the prostate: changing incidence associated with annual urologic screening. AB - The Urology Service at Brooke Army Medical Center has conducted routine screening rectal examinations for early diagnosis of carcinoma of the prostate since 1979. A review of the incidence of carcinoma of the prostate reveals that routine screening has yielded a significant increase in disease incidence. This incidence appears higher than national averages. It is apparent that a commitment to early diagnosis through screening for carcinoma of the prostate also requires a commitment in medical resources. PMID- 2922624 TI - Tracheoesophageal compression syndromes related to vascular ring. AB - Seventeen cases of vascular ring have been encountered at Ochsner Clinic over the past 22 years. Anatomic configurations consisted of double aortic arch in 11 cases, right aortic arch with left ligamentum arteriosum in five cases, and aberrant right subclavian artery in one case. In four cases chest x-ray films revealed air block or hyperinflation and led to further diagnostic tests. The definitive diagnostic methods included esophagogram in 15 cases, aortography in 14 cases, two-dimensional echocardiography in one case, and esophagoscopy/bronchoscopy in eight cases. Presenting symptoms were respiratory in 13 cases and feeding difficulties in three; one asymptomatic case was found incidentally. Four cases of air block syndrome were observed as an early and unusual presentation of vascular ring in infants. Hyperinflation of the lung fields on chest x-ray film should spur suspicion of a possible vascular ring. Two case reports are included to demonstrate air block in relation to vascular rings in neonates. PMID- 2922625 TI - Nurse-initiated health promotion prompting system in an internal medicine residents' clinic. AB - Although cure of many diseases depends on early detection, screening schemes have been difficult to implement in busy clinic environments. We describe the testing of a nurse-initiated prompting system for six health promotion and disease prevention procedures in an internal medicine residents' clinic at a university affiliated community program. Maneuvers investigated were breast examination, pelvic examination and Pap smear, rectal examination in men, mammogram, stool guaiac test, and blood glucose determination. A nurse reviewed the charts and used a list in the front of each chart to prompt residents in the experimental group. Residents in the control group were not prompted. A significant improvement (P less than .05) in performance was seen in the prompted group. Performance of rectal examination and mammograms improved most, increasing from 41% to 93% and 18% to 64%, respectively. There were no significant changes in the control group. This simple nurse-initiated prompting system improved the performance of health promotion and disease prevention maneuvers. PMID- 2922626 TI - Why perform a routine history and physical examination? AB - Science uses two types of data--one for generating hypotheses and a second for testing hypotheses. In clinical medicine the history and physical examination generate the data used for making hypotheses about what could possibly be wrong with the patient; but the various laboratory and imaging procedures are used for hypothesis-testing, ie, deciding which of the possible problems is actually the one bothering the patient. Although comparisons between physical examination maneuvers and imaging procedures may tell something about the precision of the former, in general such comparisons can tell little about the intrinsic worth of one versus the other, because these two different types of procedures generate data with two completely different types of usage. PMID- 2922627 TI - Methemoglobinemia and hemolytic anemia after phenazopyridine hydrochloride (Pyridium) administration in end-stage renal disease. AB - Phenazopyridine is a commonly used urinary tract analgesic. As illustrated by the case we have reported, its use may be complicated by the development of methemoglobinemia and hemolytic anemia, especially in patients with renal insufficiency. PMID- 2922628 TI - Polyglandular autoimmune syndrome, type 2. AB - We have described two patients with Addison's disease and associated endocrinopathies, a condition termed polyglandular autoimmune (PGA) syndrome, type 2. One of our patients also had autoimmune hypothyroid disease, and the other had premature gonadal failure and Hashimoto's thyroiditis. This syndrome shows that glandular disorders tend to occur together. It has been suggested that an HLA-associated genetic predisposition coupled with environmental factors triggers an autoimmune process resulting in glandular hypofunction or hyperfunction. We stress the necessity for evaluation of every individual with idiopathic Addison's disease for associated endocrinopathies. PMID- 2922629 TI - Acute bilateral diffuse pulmonary shadowing after evacuation of hydatid mole. AB - Acute bilateral diffuse pulmonary shadowing complicates the resection of hydatid mole approximately 10% of the time. Etiologic factors include trophoblastic emboli, pulmonary emboli, high output congestive failure, and DIC. Prompt recognition and emergency oxygen therapy with PEEP are imperative for survival. PMID- 2922630 TI - Secondary adrenal insufficiency manifested as an acute febrile illness. AB - High fever occurred in a 30-year-old woman five weeks after transsphenoidal hypophysectomy for a pituitary adenoma. Extensive investigation failed to reveal any evidence of infection, and the clinical findings suggested the fever to be a manifestation of steroid withdrawal. Either suboptimal dosage of corticosteroid replacement therapy or omission of such therapy in adrenal insufficiency must be considered in the differential diagnosis of enigmatic postoperative fever. PMID- 2922631 TI - Unusual chronic maculopapular rash associated with human immunodeficiency virus infection. AB - A 21-year-old black man with sickle cell disease who has received blood transfusions for 11 years because of recurrent stroke has had a decline in numbers of circulating lymphocytes and T4 cells over the past four years. Two and a half years ago persistent generalized lymphadenopathy developed, associated with a positive test for human immunodeficiency virus (HIV) antibody. For the past seven months he has had a pruritic maculopapular rash, primarily on the extensor surfaces of the extremities. Multiple skin biopsies revealed only nonspecific perivascular infiltrates of mononuclear cells. This rash appears to be an unusual manifestation of HIV infection, and may be an indicator of impending AIDS. PMID- 2922632 TI - Aneurysm of the internal iliac vein as a rare source of pulmonary thromboembolism. AB - This is the first reported case of internal iliac vein aneurysm, manifested by recurrent pulmonary embolism. The case emphasizes the importance of searching for unusual sources of unexpected and unexplained pulmonary emboli. Venous aneurysms may have various manifestations and sequelae. Antecedent trauma and arteriovenous fistulas should be excluded. PMID- 2922633 TI - Cryptococcal meningoencephalitis presenting transient focal cerebral symptoms. AB - Cryptococcal meningoencephalitis (CM) is a fatal disease if untreated. We have presented an unusual case of CM clinically diagnosed as transient ischemic attacks. Therapy with amphotericin B and flucytosine cured the infection and the patient had no further episodes of transient focal cerebral dysfunction. In patients with transient focal cerebral symptoms, study of the cerebrospinal fluid may prove helpful. PMID- 2922634 TI - Yersinia enterocolitica causing spinal osteomyelitis and empyema in a nonimmunocompromised host. AB - We have reported a case of spinal osteomyelitis and empyema caused by Yersinia enterocolitica. Because this patient was in otherwise good health without evidence of liver disease, the extent of her illness was remarkable. This unique report of Y enterocolitica infection of the spine not only illustrates the organism's capacity for hematogenous spread in nonimmunocompromised patient, but documents survival in the face of widely disseminated multisystemic disease. Furthermore, the management of this patient was unusual in that operation was required. The astute clinician should consider the possibility of spinal involvement in a patient with Yersinia colitis and neck pain and should also recognize the possibility of serious and widespread infection in an otherwise low risk patient. In a patient with widespread disease, focal collections of fluid may necessitate surgical management. PMID- 2922635 TI - Acute inguinal lymphadenitis associated with Yersinia enterocolitica. PMID- 2922636 TI - Movements of the sacroiliac joints. A roentgen stereophotogrammetric analysis. AB - Twenty-five patients (21 females and 4 males) with sacroiliac joint disorders were studied with roentgen stereophotogrammetry in physiologic positions as well as in the extreme of physiologic positions. There was a constant pattern of motion with different load, especially around the transverse axis. The rotations were small and in mean between position 2.5 degrees (0.8 degree-3.9 degrees). The translation was, mean, 0.7 mm (0.1-1.6 mm). There was no difference between symptomatic and asymptomatic joints. PMID- 2922637 TI - Biochemical and structural properties of the cartilage end-plate and its relation to the intervertebral disc. AB - The cartilaginous end-plate is thought to play an important role in the nutrition of the intervertebral disc, and hence may be of significance in the etiology of back pain. The present study describes the biochemical and histologic properties of the end-plate and adjacent tissues in the young human adult lumbar spine. Thus, a datum is established in which to demonstrate variation with location and relationships between properties of different tissues. Results of the chemical analyses show a change in composition through the end-plate with that at the outer annulus and nearer the bone, having higher collagen but lower proteoglycan and water contents, than the end-plate nearest the disc at the nucleus. Histology demonstrated numerous disruptions along the end-plate, with Schmorl's nodes being present in several specimens. Where these occurred, the disc, and in some cases the end-plate, showed loss of proteoglycan compared with the surrounding tissue. PMID- 2922638 TI - Measurement of human lumbar spine ligaments during loaded and unloaded motion. AB - Length changes in the ligaments of human lumbar spine motion segments were investigated in order to find conditions under which unusual stress or stress reduction is found in the longitudinal ligaments and facet joint capsules. Flexibility measurements were performed under load. Increasing load and height reduction in the motion segment increases the flexibility. The anterior and posterior longitudinal ligament normally operate in the elastic part of their stress-strain curve. Destruction of the intervertebral disc leads to a dislocation of the centers of rotation in the motion segment. Two types of facet joint capsules were observed. Height reduction in the motion segment leads to abnormal strains in one type sooner than in the other, which can be normalized by slight flexion. Injection of a silicone compound into the disc normalizes many of the changes in the motion segment due to height reduction. PMID- 2922639 TI - The geometry of the muscles of the lumbar spine determined by magnetic resonance imaging. AB - Magnetic Resonance Imaging (MRI) is a new multiplanar imaging technique that clearly demonstrates soft tissue anatomy. The lumbar spines of 26 males have been scanned. From the transverse scans, the position and cross-sectional areas of the muscles of the lumbar region were recorded. Regression analysis was performed to relate these values to trunk measurements and body weight. Sagittal scans were used to measure the angles to the vertical of the lumbar discs and of the skin overlying the spinous processes. The position of each lumbar disc relative to two skin points was measured. These parameters can then be used in biochemical calculations of low-back forces. PMID- 2922640 TI - Spinal stability and intersegmental muscle forces. A biomechanical model. AB - The human spinal column, devoid of musculature, is incapable of carrying normal physiologic loads. In an in vitro experiment, the effect of simulated intersegmental muscle forces on spinal instability was investigated. Intact and sequentially injured fresh lumbar functional spinal units were subjected to three dimensional biomechanical tests with increasing muscle forces. With the application of muscle forces, range of motion (ROM) increased and neutral zone (NZ) decreased in flexion loading, while both ROM and NZ decreased in extension loading. In lateral bending, ROM and NZ were unaffected by the application of the muscle forces. In axial rotation, ROM decreased significantly, while NZ decrease was statistically insignificant. It was concluded that the action of the intersegmental muscle forces is to maintain or decrease intervertebral motions after injury, with the exception of the flexion ROM, which increased with the application of muscle forces. In addition, the study suggested that Neutral Zone is a better indicator of spinal instability than Range of Motion. PMID- 2922641 TI - Physical activity and the strength of the lumbar spine. AB - The cadaveric lumbar spines of nine young men killed in road accidents were subjected to a range of mechanical tests, and the results compared with the men's occupational and recreational histories. It was found that the compressive strength of the spines tended to increase with the level of physical activity in life, but the increase was significant only in the eight spines aged 18 or over. Compressive failure usually occurred in the vertebral body, but in three cases, the disc prolapsed into the vertebral canal; these discs came from three of the four most physically active individuals. It is concluded that physical activity strengthens both the vertebrae and the discs. A high level of activity can cause vertebral strength to exceed that of the discs. PMID- 2922642 TI - Spinal mobility in adolescent girls with idiopathic scoliosis and in structurally normal controls. AB - Spinal mobility and posture were studied in 29 adolescent girls (mean age, 13.9 years) with thoracal idiopathic scoliosis, and in 30 healthy girls (mean age, 14.0 years) of the same age. Measurements of the mobility were conducted by inclinometers and a compass in three planes; sagittal, frontal, and horizontal. The structurally healthy girls were taller and heavier than the scoliotics; the difference was statistically significant for weight (P less than 0.01). The positional inclines of sacrum, upper lumbar and thoracic areas were significantly smaller in the scoliotics, resulting in smaller lumbar lordosis and thoracic kyphosis in them (P less than 0.001). In the thoracic spine, forward flexion was smaller (P less than 0.01), whereas extension (P less than 0.001) and the total sagittal mobility (P less than 0.01) were greater in the scoliotics. In the healthy controls, the thoracic clockwise rotation was significantly (P less than 0.05) larger than the counterclockwise. This side difference had disappeared in the scoliotics, and their total thoracic rotation was indicatively smaller than in the controls. In the lumbar spine, extension was smaller (P less than 0.01) in the scoliotics than in the controls. All spinal mobility measurements noted there was no change of general spinal flexibility in the scoliotics. PMID- 2922643 TI - Segmental wiring for spinal deformity. A morbidity report. AB - Members of the British Scoliosis Society were circulated a questionnaire in order to establish the morbidity of surgery for spinal deformity in the years 1983 and 1984 in Great Britain. Surgeons were asked to report the complications relating to all types of surgery for spinal deformity in order to establish the relative morbidity of segmental spinal wiring. Of the 1,121 patients reported, 1.4% suffered neurologic complications. In straightforward surgery for adolescent idiopathic scoliosis, there were four serious neurologic complications: three with Harri-Luque and one with routine Harrington distraction instrumentation. A plea is made that morbidity studies of spinal deformity surgery should compare all types of instrumentation and should be sufficiently detailed to allow statistical comparison. PMID- 2922644 TI - Meningeal skin fistula. A complication following Harrington rod instrumentation and segmental wiring. PMID- 2922645 TI - Fibrous dysplasia of the axis. A case report. PMID- 2922646 TI - Nicardipine after spinal cord compression in the lamb. AB - To study the effects of the calcium channel blocker nicardipine on spinal cord blood flow and spinal evoked potentials, the following study was undertaken. After cord compression, which was productive of paraparesis, nicardipine was administered intravenously in 10 anesthetized lambs. Ten control animals were subjected to compression but received saline instead. Nicardipine produced a significant decrease in mean arterial pressure when compared to the control group. Thirty minutes after compression, spinal cord blood flow also was lower in the nicardipine group compared with controls. Spinal evoked potentials did not recover after compression in either group. PMID- 2922647 TI - New headache classification. PMID- 2922648 TI - Stroke, myocardial infarction, and survival during long-term follow-up after carotid endarterectomy. AB - Epidemiological data on 211 patients undergoing 256 carotid endarterectomies were reviewed, and current data for the 205 perioperative survivors were analyzed by the actuarial method. The median follow-up period was 7.0 years (range: 1 month to 23.2 years). Seven percent of patients were lost to follow-up. Actuarial survival was 77% (5 years) and 49% (10 years), but lower than for the general population. Late stroke occurred in 27 patients (13%) (fatal in 9), being ipsilateral to an endarterectomy in only 10 (4.9%). The annual ipsilateral stroke rate (0.41%), comparable to that of the general population, suggests protection from subsequent stroke. Myocardial infarction occurred in 69 patients (34%), and accounted for 49% of late deaths. PMID- 2922649 TI - HMOs: the failed promise. PMID- 2922650 TI - Brain abscess associated with congenital heart disease. AB - Between 1952 and 1985, 25 cases of brain abscess with congenital heart disease were treated at the Department of Neurosurgery, Tianjin Medical College Hospital. Patients' ages ranged from 5 to 38 years. The most common form of congenital heart disease was tetralogy of Fallot, occurring in 13 cases. The abscesses were located in the parietal, frontal, and temporal lobes. The pus from the abscesses was sterile in 13 of 19 cases. In the rest, Streptococcus was the predominant organism. Twenty-three cases were treated by aspiration of the abscess through a burr hole. In two cases, initial aspiration was followed by excision of the abscess. The mortality rate of the whole group was 32%. The etiology of brain abscess in patients with congenital heart disease is discussed. PMID- 2922651 TI - A cause and cure of some cases of "writer's cramp". AB - Writer's cramp is a very disabling condition characterized by difficulty in fine movements of the hand such as writing, shaving, or performing surgery. It is associated with pain in the forearm and upper arm. Women with writer's cramp experience comparable difficulty. An analysis of 100 cases of ruptured C6 disk, proved at operation and taken at random from the files of Semmes-Murphey Clinic, was carried out, and showed that 60 of these had pain in the right arm and 40 had pain in the left arm. Twenty of those with right arm pain had writer's cramp. There was one questionable case of writer's cramp in the left arm. Of the 20 who had writer's cramp, 13 had complete relief of writer's cramp and pain, 1 had no relief (Dr. Butts), and there were 6 lost to follow-up. At least one cause of writer's cramp is suggested, but no claim is made that this is the only cause. PMID- 2922652 TI - Intraspinal melanotic arachnoid cyst and lipoma in neurocutaneous melanosis. AB - A 22-year-old woman with neurocutaneous melanosis is reported in whom an intraspinal melanotic congenital arachnoid cyst and melanotic lipoma occurred at the same thoracic location. Such combined occurrence of lesions of the central nervous system, producing compression of the spinal cord, has not been noted in any previously reported case of neurocutaneous melanosis. The pathogenesis of these two unusual melanotic lesions is discussed in relation to the ectomesenchymal properties of the neural crest. The concurrent melanotic arachnoid cyst and lipoma, in juxtaposition, were demonstrated by a computed tomography scan in which the preoperative diagnosis of lipoma was possible through the density of the lesion. PMID- 2922653 TI - Removal of an arteriovenous malformation in the optic chiasm. A case of Bonnet Dechaume-Blanc syndrome without retinal involvement. AB - A rare case of an arteriovenous malformation involving the optic chiasm associated with vascular anomaly in the left maxillary region is presented. The angiogram demonstrated an arteriovenous malformation arising from the anterior circle of Willis (internal carotid, posterior communicating, and proximal anterior cerebral arteries), and located in the region of the optic chiasm and hypothalamus. The case was diagnosed as the Bonnet-Dechaume-Blanc syndrome without intraorbital and retinal arteriovenous malformations. The suprasellar arteriovenous malformation was removed, except for a small portion in the hypothalamus, with satisfactory results. PMID- 2922655 TI - The longest lasting legacy. PMID- 2922654 TI - Intracranial mycotic aneurysm associated with transsphenoidal surgery to the pituitary adenoma. AB - A case is reported in which a mycotic aneurysm of the supraclinoidal portion of the internal carotid artery formed as the result of suprasellar infection following transsphenoidal surgery. The source of infection was thought to be a maxillary sinusitis. The aneurysm was treated with systemic antibiotic therapy and disappeared 4 months after the operation. Repeated angiography showed the whole course from the formation to the disappearance of the aneurysm and was valuable in the treatment of intracranial mycotic aneurysms. PMID- 2922657 TI - The neurosurgeon as chairman of surgery. PMID- 2922656 TI - Surgical repair of aneurysms of the posterior inferior cerebellar artery--a clinical series. AB - Aneurysms of the posterior inferior cerebellar artery are relatively rare. Fourteen such aneurysms (10 vertebral, 4 peripheral) are reported, and their clinical presentation, surgical therapy, and outcome are discussed. All 14 patients had suffered a subarachnoid hemorrhage; 93% (n = 13) underwent direct clipping of the aneurysm while 7% (n = 1) underwent coating of the aneurysm. Two patients died in the perioperative period (one from vasospasm and one from rebleeding). Full activity was achieved by all but one (92%) of the remaining patients in extended follow-up. PMID- 2922658 TI - Immunocytochemical evidence of progesterone receptors in human meningiomas. AB - The presence of progesterone receptors in meningioma tissue is demonstrated by use of highly specific monoclonal antibodies against the rabbit progesterone receptors which cross-react with human progesterone receptors in breast cancer cells, thus giving evidence of the existence of genuine progesterone receptors in human meningiomas. PMID- 2922659 TI - Cerebral resuscitation with succinate and fructose-1, 6-diphosphate. AB - To test the hypotheses that succinate or fructose-1, 6-diphosphate may have a beneficial effect in global cerebral ischemia, we induced complete global cerebral ischemia for 5 minutes in rabbits by occlusion of the ascending aorta and the superior and inferior vena cavae. Fifteen minutes after restoration of cerebral blood flow, animals received an intravenous bolus of either succinate or fructose-1,6-diphosphate followed by continuous infusion. Another group of animals received fructose-1, 6-diphosphate beginning prior to aortic occlusion. Control animals received intravenous glucose by bolus, followed by infusion. Cerebrospinal fluid lactate levels were measured before occlusion and at 2 1/2 hours after occlusion, when the animals were sacrificed. In all animals electrocortical silence was demonstrated for the 5 minutes of global ischemia. The percent change in cerebrospinal fluid lactate levels in all groups was statistically similar. Only two of seven of the control animals recovered electroencephalogram amplitude during the 2 1/2 hour observation period. Time for recovery of amplitude on the electroencephalogram in animals receiving fructose 1, 6-diphosphate either before or after ischemia was statistically similar to controls. In the succinate treated group, all seven animals regained preocclusion levels of electroencephalogram amplitude within 36 minutes of the restoration of cerebral blood flow. Succinate administered after complete global cerebral ischemia resulted in significantly increased recovery of cerebral electrical activity (Fischer's exact test, p less than 0.05). PMID- 2922660 TI - Effects of hypercapnia on cerebral blood flow following prophylactic and delayed experimental superficial temporal artery-middle cerebral artery bypass. AB - Cerebral blood flow was studied in dogs to ascertain whether preexisting superficial temporal artery-middle cerebral artery bypass could preserve hypercapnic reactivity following acute ischemia and whether postischemic-delayed revascularization would restore hypercapnic reactivity. In six dogs flow was preserved and some degree of hypercapnic response remained following proximal occlusion with a patent bypass. During complete ischemia (bypass occluded) there was no hypercapnic reactivity in the ischemic zone. Significant flow was restored to the ischemic area following bypass reopening, but a cerebral blood flow decrease was seen with subsequent hypercapnia. In the opposite (control) hemisphere hypercapnia always produced significant cerebral blood flow increases. These data support the superiority of prophylactic over delayed superficial temporal artery-middle cerebral artery bypass in appropriate clinical situations. PMID- 2922661 TI - Effect of the nonglucocorticoid 21-aminosteroid U74006F experimental cerebral vasospasm. AB - The present work was performed to establish whether the nonglucocorticoid, 21 aminosteroid, U74006F, could prevent the development of delayed cerebral vasospasm after experimental subarachnoid hemorrhage. The subarachnoid hemorrhage was produced by percutaneous injection of 4.5 mL of nonheparinized autologous blood into the cisterna magna of rabbits. U74006F (1 mg/kg) or placebo was injected intraperitoneally every 12 hours starting 12 hours prior to induction of hemorrhage for a total of six doses. The animals were sacrificed by perfusion fixation. The basilar artery was removed on day 2 and processed for morphometric analysis. Control/placebo and subarachnoid hemorrhage/placebo basilar artery diameters were 651.2 +/- 25.4 and 366.3 +/- 34.2 mu, respectively. Control/U74006F basilar artery diameters (669.8 +/- 21.8 mu) were not significantly different from that of the control/placebo group. U74006F treatment greatly minimized subarachnoid hemorrhage-induced reduction in mean luminal diameter (563.7 +/- 48.2 mu) (p less than 0.001). These results demonstrate considerable therapeutic promise for U74006F in the prevention of cerebral vasospasm. PMID- 2922662 TI - Effect of blood flow rate and donor vessel diameter on the patency of carotid venous bypass grafts in dogs. AB - A saphenous vein graft was implanted from the right subclavian to the right common carotid artery in seven dogs (group I) and between the right and left common carotid arteries in another seven dogs (group II). The recipient artery was ligated proximally to augment blood flow through the graft. Immediately after the anastomoses were completed, the average blood flow through the graft was 32 +/- 25 mL/min in group I and 122 +/- 22 mL/min in group II. At sacrifice 30 days later, angiography showed that all grafts in group I were thrombosed, whereas six (87.5%) of seven grafts in group II were patent. These findings suggest that a larger donor vessel diameter and higher graft flow rates may improve patency in venous bypass grafts that are 3 to 5 mm in diameter. PMID- 2922663 TI - Early berry aneurysm formation in Marfan's syndrome. AB - A detailed study of cerebral arterial forks by serial sectioning was made in a 33 year-old woman with typical Marfan's syndrome who died of septicemia following cardiac surgery. Two forks of the right middle cerebral artery exhibited the atrophic changes associated with early berry aneurysm formation indicating that the mode of development of these aneurysms is similar in both Marfan's syndrome and in non-Marfan subjects. PMID- 2922664 TI - Focal brain ischemia model in rats. An experimental study. AB - Using 74 male rats, anatomical variations of branching of the proximal segment of the middle cerebral artery were studied. In 36 rats (28 Sprague-Dawley rats and eight spontaneously hypertensive rats), the middle cerebral artery and/or its branches were occluded at various sites. Occlusion of the middle cerebral artery at the lateral border of the olfactory tract with or without simultaneous ligation of the ipsilateral common carotid artery rarely caused cerebral infarction in Sprague-Dawley rats. Occlusion of the olfactory branch in addition to the trunk of the middle cerebral artery caused large infarction of the pallium in five of eight Sprague-Dawley rats. Occlusion of the middle cerebral artery at the medial border of the olfactory tract caused infarction in the pallium and/or basal ganglia in five of six rats, and neurologic deficits were severe and persistent. Occlusion of the middle cerebral artery at the lateral border of the olfactory tract in spontaneously hypertensive rats caused large infarction with severe neurologic deficits in all eight animals. Possible factors responsible for such diverse differences and the relative value of each group as an experimental model of focal cerebral ischemia in rats were discussed. PMID- 2922665 TI - Hypersensitivity reaction associated with sterile ventriculoperitoneal shunt malfunction. AB - Infection and obstruction remain significant problems associated with shunts. We studied the clinical and pathological findings in 29 patients who underwent surgical procedures to revise malfunctioning ventriculoperitoneal shunts. The preoperative diagnosis for shunt malfunction was infection in 8 cases, and obstruction in 18 cases. A pathologist NK independently examined the shunt hardware removed from the patients without knowledge of the clinical diagnosis. There were 19 ventricular catheters, 15 valves, and 14 abdominal catheters examined. Fourteen of the patients had had three or more shunt revisions. Three of these patients had evidence of some hypersensitivity reaction due to the shunt hardware (multiple eosinophils and giant cells in tissue enveloping shunt hardware). Of the 15 patients who had two or less shunt revisions, none had evidence of hypersensitivity on pathological examination of the shunt hardware. We conclude that pathological examination of shunt hardware is helpful in understanding noninfectious causes of shunt malfunction. We have identified a subgroup of patients who developed a hypersensitivity-like reaction around the shunt that in certain instances may lead to shunt malfunction. It is important to identify these patients for they may be more likely to have multiple episodes of shunt malfunction. PMID- 2922666 TI - Gadolinium-DTPA enhancement of a recurrent intramedullary ependymoma: a case report. AB - Magnetic resonance images enhanced with the paramagnetic contrast agent gadolinium-DTPA accurately differentiated a recurrent intramedullary spinal cord ependymoma from surrounding postoperative and postirradiation spinal cord tissue changes, thereby facilitating total excision of the lesion. The illustrative case and the merits of enhanced magnetic resonance imaging are presented. PMID- 2922667 TI - Spinal cord damage caused by rotation of a T-drain in a patient with syringoperitoneal shunt. AB - We report on a severe complication to the use of intramedullary T-drain in syringoperitoneal shunting procedures: rotational forces in the shunt system causing the arms of the T-drain to gradually compress spinal cord tissue and damage it. Further rotation/destruction was prevented by removing the distal part of the drain system, and by separating the two arms of the T-drain, thus changing it into a syringosubarachnoidal shunt. The syrinx remained collapsed throughout all procedures. PMID- 2922668 TI - Hypothalamic and basal forebrain germinoma presenting with amnesia and hyperphagia. AB - Patients harboring primary intracranial germinomas usually have had Parinaud's syndrome and hydrocephalus (with pineal tumors) or hypopituitarism, visual loss, and diabetes insipidus (with suprasellar tumors) at presentation. The few reported cases of verified intraparenchymal hypothalamic germinomas all have been in prepubertal males with progressive neurologic deficits, altered levels of consciousness, or clinically apparent panhypopituitarism. The subject of this report was an endocrinologically normal, primiparous 24-year-old woman who presented with hydrocephalus followed by worsening anterograde amnesia and hyperphagia despite having a functioning ventriculoatrial shunt. Computed tomography scanning and magnetic resonance imaging demonstrated an anterior hypothalamic, thalamic, and basal forebrain mass, which stereotactic biopsy proved to be a germinoma. Intraaxial germinomas restricted to the anterior hypothalamus or thalamus rarely have been reported. The clinical features of the current patient may be unique. PMID- 2922669 TI - Metastatic Ewing's sarcoma to the brain: case report and review of treatment. AB - An unusual case of Ewing's sarcoma metastatic to the brain is presented. Neurosurgical intervention has a role in the treatment of patients with central nervous system metastasis of this rare tumor. PMID- 2922670 TI - Synovial cyst at the craniovertebral junction. AB - A case of synovial cyst of the upper cervical spine that resulted in spastic quadriparesis and sensory loss is reported. Radiographic evaluation included a computed tomography scan after myelography and a magnetic resonance imaging scan. The synovial cyst was removed by a laminectomy at C-1 and C-2, combined with a foramen magnum craniectomy. The patient had a good recovery. PMID- 2922671 TI - The course of the internal carotid artery. PMID- 2922672 TI - Continued progress against cardiovascular diseases. PMID- 2922673 TI - Prospective comparison of gastric secretory function after gastrectomy with either Billroth II or Roux-en-Y anastomosis. AB - In order to delineate the role of enterogastric reflux in changes of postoperative gastric secretory functions, 22 patients with peptic ulcers, who were randomly assigned to partial gastrectomy without vagotomy with either Billroth II or Roux-en-Y anastomosis, were prospectively studied before and 6 months after surgery. Preoperatively, there were no significant differences in gastric secretory functions between the two groups of 11 patients. Postoperatively, median fasting bile acids in the stomach increased in the Billroth II patients from 0.35 to 16.10 mumol/hr (p less than 0.01), but significantly decreased in the Roux-en-Y patients from 0.30 to 0.10 mumol/hr (p less than 0.05), which indicated adequate prevention of enterogastric reflux after the Roux-en-Y procedure. Gastrectomy resulted in significant reductions of median values of basal acid output (4.6 vs 0.6 mmol/hr, p less than 0.01, and 4.2 vs 0.4 mmol/hr, p = 0.02), peak acid output (31.6 vs 4.2 mmol/hr, p less than 0.01, and 38.7 vs 4.5 mmol/hr, p less than 0.01), serum pepsinogen A (121 vs 86 micrograms/L, p less than 0.01, and 92 vs 45 micrograms/L, p less than 0.01), meal-stimulated serum gastrin secretion (1472 vs 199 pM.60 min, p less than 0.0001, and 1017 vs 199 pM.60 min, p less than 0.0001) in the patients with Billroth II and Roux-en-Y anastomosis, respectively. There were, however, no significant differences in gastric secretory parameters between the two groups when studied 6 months after surgery. Therefore it is concluded that after gastrectomy, enterogastric reflux does not affect the secretory function of the gastric remnant within the first 6 months after surgery. PMID- 2922674 TI - The dilemma of outcome assessment after operations for morbid obesity. AB - Outcome of 56 patients who underwent horizontal gastroplasty (HGP) and 126 who underwent Roux-en-Y gastric bypass (RYGB) was assessed at 18 months postoperatively according to three definitions of successful weight loss; also, outcome was evaluated in the context of amelioration of obesity-related medical problems. Outcome definitions included the following: I, loss of 25% or more of preoperative weight; II, loss of 50% or more of excess weight; III, loss to within 50% of ideal body weight. To evaluate the impact of preoperative weight on success rate, patients were divided into two weight groups: "morbidily" obese patients, who were 100 to 199 pounds overweight (n = 146), and "super"-obese patients who were 200 pounds or more overweight (n = 36). Weight loss was significantly greater with RYGB versus HGP by each of the three definitions of success. Medical problems either improved or resolved with weight loss in 95% of cases. There were statistically significant differences in success rate depending on outcome definition in both HGP and RYGB patients. Success rate ranged from zero in super-obese HGP patients by Definition III to 97% in super-obese RYGB patients by Definition I. Although super-obese patients lost more pounds than the lighter morbidly obese patients, a significantly lower number of super-obese patients lost within 50% of ideal weight. Super-obese patients must lose more weight to reduce their actuarial risk. These results show that the definition of successful outcome may significantly influence the overall success rate in a large series of bariatric surgical patients. PMID- 2922675 TI - Is proximal pancreatoduodenectomy with pyloric preservation superior to total pancreatectomy? AB - The records of all patients who underwent pylorus-preserving pancreatic resection (29 subtotal and 4 total pancreatectomies) during a 10-year period at the Mayo Clinic were reviewed. Thirty-day operative mortality was 6%. Early postoperative morbidity occurred in 45% of patients and necessitated reoperation in four patients. One patient had a hemorrhage from a marginal ulcer in the early postoperative period. The incidence of late postoperative morbidity was 18%. Marginal ulcers developed in the late postoperative period in three additional patients, for an overall incidence of 13%. One patient underwent vagotomy and pyloroplasty because of intractable bleeding 2 years after initial operation. The 29 patients who underwent pylorus-preserving pancreatoduodenectomy (PPW) were compared (retrospectively) with 200 patients who had undergone standard pancreatoduodenectomy (Whipple operation) during the same 10-year period. The overall incidences of marginal ulcer were 10% in the PPW group and 5% in the Whipple group; the incidences of delayed gastric emptying were similar in these groups. We believe that caution is warranted in the use of PPW, as yet an unproved procedure. PMID- 2922676 TI - Risk factors of postoperative pulmonary complications after vascular surgery. AB - Smoking and chronic obstructive disease are common in patients who undergo vascular surgery. These patients seem especially at risk for postoperative respiratory complications (PRCs). The value of preoperative spirometric tests to determine the risk of PRC has been recently challenged. The current prospective study was undertaken to identify the risk factors of PRC in these patients. One hundred fifty-one patients, including 67 patients who underwent abdominal aortic surgery, were included in this study. Preoperative and peroperative parameters were collected and analyzed in a multivariate analysis. PRCs were classified as minor and major. A significantly prolonged postoperative hospital stay was associated with major complications (21.3 +/- 9.0 vs 14.3 +/- 6.0 days). The overall incidence of PRC was 37.1%, and the incidence of major PRC was 15.2%. Patients who underwent abdominal aortic surgery had a higher incidence of PRC (53%; major PRC, 24%). In addition to abdominal aortic surgery, other risk factors were chest deformation, recent bronchitis, duration of surgery, and FEV1/VC. In patients who underwent abdominal aortic surgery, the risk factors for major PRC were decreases in preoperative FEV1/VC and PaO2. This study confirms the importance of an evaluation of a patient's respiratory condition, especially by preoperative spirometry and blood gas analysis, to determine the risk of PRC in a given population. General risk factors, such as the American Society of Anesthesiologists' classification, fail to achieve this task. The identification of patients with unacceptable risks remains a challenge. PMID- 2922677 TI - Mechanical factors predisposing to intimal hyperplasia and medial thickening in autogenous vein grafts. AB - Autogenous veins undergo intimal hyperplasia and medial thickening when used as arterial bypass grafts. Exposing veins to arterial pressure and flow subjects them to three static deformations, three static stresses, increased pulsatile deformations, pulsatile stresses, and altered shear stress at the blood-intima interface. All of these occur simultaneously; thus it is unclear which of these nine mechanical factors predispose to the histologic changes that occur in the vein wall. Three sequential experiments were performed in 38 dogs to determine the role of each of these factors. Results showed that intimal hyperplasia is best associated with low flow velocity, a factor correlated with low blood-artery shear stress. By contrast, medial thickening is best associated with increased deformation of the vein wall in the circumferential direction (increased diameter). These findings correlate with clinical responses of vein grafts. PMID- 2922678 TI - Reconstruction of a functional hemidiaphragm with use of omentum and latissimus dorsi flaps. AB - After ablative surgery that involves the diaphragm, autologous tissue is the material of choice for reconstruction--particularly if adjuvant radiotherapy is planned. Latissimus dorsi muscle and omentum are reliable sources of such tissue. A case is reported describing a method of diaphragm reconstruction after resection by mobilization of the upper latissimus dorsi and passing the free muscle portion over the residual costal margin to form a neodiaphragmatic leaflet. Suture of the transposed latissimus free end to the residual diaphragm tendon and the use of omentum to fill defects residual after muscle transposition were used to complete the reconstruction. PMID- 2922679 TI - Transhepatic embolization of superior mesenteric varices in portal hypertension. AB - A 49-year-old woman with a history of excessive consumption of alcohol experienced lower-intestinal bleeding 2 years after undergoing a total abdominal hysterectomy and salpingo-oophorectomy because of carcinoma of the cervix. Mesenteric arteriograms showed large, focal varices in the ileum, hepatofugal blood flow, and an abnormal communication between these varices and the right ovarian vein. Percutaneous transhepatic embolization of these varices with absorbable, gelatin sponge (Gelfoam) and coils was successful in stopping the intestinal bleeding. PMID- 2922680 TI - Axillary compression syndrome with neurapraxia due to operative positioning. AB - A 20-year-old man underwent a 9-hour operation in a left lateral position for the removal of an osteoblastoma involving the pedicles of thoracic vertebrae T-11 and T-12 and for fixation with bond grafting. Immediately after the operation, extensive swelling of the left shoulder area was noted. The radial pulse on the left was intact, and there was movement of the fingers of the left hand, which ceased completely by the following morning. A computerized axial tomographic scan showed extensive swelling of the pectoral, deltoid, and other muscles around the shoulder. An emergency decompression procedure was carried out by dividing the pectoral and anterior scalene muscles; prompt return of some motor activity in the left hand followed, and this gradually returned to normal. This case of what may be termed "axillary" compression syndrome suggests that extra care should be taken to use an adequate axillary roll and to avoid lengthy operations in a lateral position, and indicates a method for decompression. PMID- 2922681 TI - Complications in cardiac transplant patients requiring general surgery. PMID- 2922682 TI - Regional anesthesia for certain patients undergoing thyroid and parathyroid surgery. PMID- 2922683 TI - Managing a 13-year-old boy with blunt abdominal trauma. PMID- 2922684 TI - Adrenaloma: a better term than incidentaloma. PMID- 2922685 TI - Aspects of dental plaque formation with special reference to colloid-chemical phenomena. AB - In order to investigate factors of importance for plaque formation and the rate of plaque formation 133 randomly selected individuals went through a 3-day period of plaque accumulation. From these individuals one group of "heavy" and one group of "light" plaque formers were selected for further studies. These subjects were investigated with reference to clinical, biochemical, biophysical and microbiological variables, that in the literature have been suggested to influence plaque formation. The collected data were analysed statistically both by comparisons between the two groups and by multiple regression. In the comparative analyses there were only minor differences between the groups, and no single studied variable was considered as the only explanation to the great difference in the amount of plaque formed after 3 days between "heavy" and "light" plaque formers. The multiple regression showed that the initial bacterial colonization of tooth surfaces was dependent on the clinical wettability of tooth surfaces, the saliva-induced aggregation of oral bacteria and finally the relative salivary flow conditions around the tooth surfaces where the bacterial samples were collected. On basis of these results, it was suggested that saliva and oral bacteria could at least partly be looked upon as being a biological colloid system system. Further studies were designed to investigate whether oral bacteria could be regarded as colloid particles or not, and to study the properties of saliva as a colloid suspending medium. These studies showed that bacteria suspended in different salt solutions were dependent on pH, ionic concentration and the valency of the cations in the solutions to be able to aggregate. The aggregating capacity further seemed to be specific for different bacterial species and strains. Addition of saliva from "heavy" and "light" plaque formers influenced the colloid stability of bacteria suspended in water in different ways. Saliva from "light" plaque formers gave a lower colloid stability in suspensions of a plaque-forming bacterium (Streptococcus sanguis) as compared to the addition of saliva from "heavy" plaque formers. No such differences were observed in suspensions of S. salivarius, which is normally not a plaque-forming bacterium. The results indicate that colloid-chemical processes might be involved in bacterial attachment to tooth surfaces, and that initial bacterial colonization of tooth surfaces at least partly follow general biophysical laws. PMID- 2922687 TI - Who needed AIDS to stay alive? PMID- 2922686 TI - Adjuvant treatment of node-negative breast cancer. AB - About half of all breast cancer patients do not have axillary nodal involvement at the time of diagnosis, and this fraction will become even larger as more women participate in screening mammography programs. Recently completed trails of limited surgery have changed the primary management of node-negative disease for many women. Now, early results from a number of carefully controlled clinical trails suggest ways in which the approach to adjuvant treatment of this disease can be improved. PMID- 2922688 TI - Reporting peer review actions to the Texas State Board of Medical Examiners. AB - This article originally was prepared for presentation at the 1988 Texas Health Law Conference, Nov 4, 1988, in Austin. It appears this month in Texas Medicine to emphasize the importance of state and federal laws that require reporting of certain peer review actions by hospitals, medical societies, and other organizations to the Texas State Board of Medical Examiners (TSBME). The author, Michael G. Young, is staff counsel for the TSBME. He formerly was staff attorney and director, Office of Medical Ethics, at Texas Medical Association. PMID- 2922689 TI - When the doctor dies. AB - This article addresses the unpleasant subject of death--the death of a physician. Unlike the demise of other professionals, a doctor's death leaves a unique set of problems for a spouse to deal with. In addition to the legal requirements of returning the license to practice medicine, both the state and federal narcotics licenses, and the triplicate prescription forms, a doctor's spouse is also responsible for disposing of office equipment and making provisions for patient records. A 12-point outline offers a guide for physicians to follow in preparing a spouse for dealing with these problems. PMID- 2922690 TI - [Current pharmacotherapy of heart insufficiency in old age]. AB - Signs of cardiovascular diseases have been found in more than 50% of elderly people over 65 years in industrialized countries. Congestive heart failure is an especially disabling consequence in up to 49% of the age-class 75 to 80 years. Treatment of these patients follows the same guidelines as in younger patients with congestive heart failure; however, treatment results are poor in many instances, and undesirable side effects are frequent. For an adequate management of congestive heart failure in the elderly, one should consider specific age related changes of the heart muscle cell, of the myocardial structure, of the vessel wall as well as functional changes of cardiovascular regulation, e.g. blunted reflexes and disturbed feed-back loops of hormonal regulation. Moreover, pharmacokinetic and pharmacodynamic properties of medicaments differ in elderly people, which should be considered for an age-adapted specific management of congestive heart failure in this patient-group. PMID- 2922691 TI - [Antibiotic therapy of bacterial pneumonia in the elderly]. AB - After reviewing the epidemiological data of mortality and morbidity of pneumonia in old people, the various mechanisms of respiratory tract infections are described. This approach points out the very important problem of nosocomial pulmonary infections. The clinical diagnosis is not easy in this high risk population whose reactions to infection are usually weak and atypical. For multiple reasons, the bacteriological proof of the infectious disease in old age is very difficult to obtain, and the adapted antibiotherapy is uncertain. The choice of the medication will also have to be based on the modified pharmacokinetics for old people. Empiric considerations are very usefull as well as the discovery of new antibiotics, but above all, it is most important not to forget the possible immunization. PMID- 2922692 TI - [The significance of exteropropioception (tactile-kinesthetic system) for verbal and nonverbal behavior following brain lesions]. AB - Brain performance is organized by complex feedback networks. Lesions disrupt and short-circuit the older phylogenetic behaviour. Recovery takes place by bridging over, essentially induced by sensory input. Given its plurality, exteroproprioception is the most powerful modality of input. A model of its stimulation ("guidance of movements in problem-solving every day tasks") reaching attention and cooperation of heavily injured patients is summarized, and arguments in favour of it are advanced. PMID- 2922693 TI - [The relation of hospital and outpatient care: an important factor in geriatric practice]. AB - An example of a way to establish contact between hospital and outpatient care was demonstrated by the method of working at a clinic for geriatrics and rehabilitation. The basis for evaluation of the working method concerning the patient is optimal information about his situation at the time of hospitalisation. An objective for the hospitalisation can be determined together with the patient. The progress achieved during hospitalisation is judged at regular intervals by the patient and the staff taking care of him. This makes an estimation of the length of required hospitalisation possible. About 40% of the patients returning to family practitioner care require outpatient care. The division between the different services involved is demonstrated. The working method was judged, based on an inquiry at the family practitioners. PMID- 2922694 TI - [Psychotherapy of the elderly adult: what are the possibilities?]. AB - A good understanding of the psychopathology of old age presupposes the knowledge of adult psychology and the theories of development. It is important to understand well the mechanisms that contributed to build up a personality in one way or an other. Old age is considered as a "stage" with specific tasks. The psychic equilibrium is constantly threatened and as well as adolescence old age must be considered as a period of great vulnerability. To face this danger energetic redistributions must take place. Sexuality and defence mechanisms are analysed by taking in account age-specific aspects. In so far as psychotherapy is concerned we shortly discuss systemic therapies but mainly the technic of supportive psychotherapy. PMID- 2922695 TI - [Pharmacotherapy and milieu therapy in senile dementia]. AB - A causal therapy is temporarily effective in one quart and permanently effective in one eighth of patients with senile dementia after precise differential diagnostic evaluation. A careful examination of the different aspects of cognition allows in all cases the recognition of the specific primary cognitive deficits and of the preserved cognitive skills. Communication of this knowledge to the relatives and the professional caregivers allows an adequate adaptation of the human and physical environment to the needs and skills of the demented. This will diminish secondary behaviour changes. The same goal has the specific pharmacotherapy of these symptoms. To minimalize side-effects, psychopharmaca in the aged have to be used less frequently, with lower doses, for shorter periods and with less different substances. PMID- 2922696 TI - [The memory clinic]. AB - The aim of the Memory Clinic, in operation at Basel since 1986, is the early detection of dementing disorders in ambulatory elderly patients. Special emphasis is put on the differential diagnosis and detection of reversible mental disorders such as depression. Treatment comprises medical, psychological and social measures. For suitable patients, drug treatment with investigational compounds is offered. Memory training programs and therapeutic groups for patients with coexisting affective disorders as well as groups for relatives are held. By these means the Memory Clinic attempts to improve the situation of elderly patients with cognitive disturbances and to maintain them longer in the community. Experience with the first 180 patients is reported. PMID- 2922697 TI - [Multidimensional assessment as a method in geriatric medicine]. AB - In regard to everyday problems with older patients on the emergency wards of our hospitals the usual diagnostic procedures are obviously not very helpful in uncovering the multiple problems these patients have. They need a comprehensive assessment which includes evaluation of the patient in several domains, namely physical, mental, socioeconomic, functional and environmental status. The multidisciplinary character of the comprehensive geriatric assessment and its problems and goals are discussed. PMID- 2922698 TI - Dephosphorylation of human fibrinogen, previously phosphorylated in vitro by protein kinase C, by whole blood or intestinal alkaline phosphatase. Effects on thrombin-induced gelation of in vitro dephosphorylated human fibrinogen. AB - Human fibrinogen, a phosphoprotein, was either left untreated or phosphorylated by protein kinase C. Then both were dephosphorylated by calf intestinal alkaline phosphatase. The dephosphorylated fibrinogen gave an increased fibre thickness during thrombin-induced gelation. Whole blood anticoagulated by heparin, EDTA or sodium citrate, contained dephosphorylating activity against 32P-labeled fibrinogen, although there were significant differences in activity among the three anticoagulants. PMID- 2922699 TI - Elastase-like activity in cultured aortic endothelial cells. AB - Cultured porcine aortic endothelial cells were studied for cellular and secreted elastase activity. We describe an activity hydrolyzing the synthetic elastase substrate, succinyl(alanine)3 nitroanilide, but not elastin, which was shown to be membrane located and was not secreted to the culture medium. A different neutral proteinase activity degrading insoluble elastin was demonstrated in the culture medium following its fractionation by gel filtration high performance liquid chromatography (HPLC). Since no elastinolytic activity could be directly detected in the conditioned medium, it is likely that the chromatographic separation removed an endogenous inhibitor. PMID- 2922700 TI - Platelet membrane glycoprotein V: characterization of the thrombin-sensitive glycoprotein from human platelets. AB - Human platelets contain a single membrane glycoprotein which is susceptible to thrombin proteolysis, glycoprotein V. We have purified 1 mg of glycoprotein V from 10(13) platelets using a combination of gel filtration, hydroxylapatite and ion-exchange chromatographies. Glycoprotein V has a blocked amino-terminus. Following proteolysis by human alpha-thrombin, a major fragment, termed glycoprotein Vf1, had the sequence Gly-Pro-Phe-X-Arg-Pro-Ala-Ala-Asp-Glu-Ser-Val Glu-Ala-Pro-Val-Asn-Gln-Al a-Glu- Ala-Pro-. The purified glycoprotein was not a substrate for human gamma-thrombin. Glycoprotein V contained 17.5% carbohydrate, with the majority of the carbohydrate consisting of neutral hexoses. Deglycosylated glycoprotein V had a molecular weight of 57.5 kDa compared to the glycosylated protein's 82 kDa and the deglycosylated protein was recognized by polyclonal antibodies raised against glycoprotein V. Immunoelectrophoresis of human and rat platelets and megakaryocytes gave a single immunoreactive band, with the rat glycoprotein having a slightly larger molecular mass. Glycoprotein V is most likely an integral membrane protein. PMID- 2922701 TI - Normalization by dietary cod-liver oil of reduced thrombogenesis in essential fatty acid deficient rats. AB - Rats, deficient in essential fatty acids (EFA), were given diets containing 5 energy% sunflowerseed oil (SO, rich in linoleic acid), cod-liver oil (CLO, rich in timnodonic acid and cervonic acid), or hydrogenated coconut oil (HCO), containing no EFAs at all. SO and CLO feeding resulted in normalization of the reduced arterial thrombus formation in EFA-deficient animals. SO feeding was associated with the normalization of the arachidonic acid content of platelet phospholipids. CLO feeding did not have this effect but greatly increased the availability of timnodonic acid (EPA) and cervonic acid (DHA). Further research is required to investigate whether these changes in fatty acid composition can be hold responsible for the normalizing effect of dietary CLO on the disturbed arterial thrombosis tendency in EFA deficient rats, possibly via the formation of eicosanoids. PMID- 2922702 TI - Structural features of heparin and their effect on heparin cofactor II mediated inhibition of thrombin. AB - Heparins from different species and tissues show similar levels of ATIII and HCII mediated anti-IIa activities. On fractionation, chains containing predominantly ATIII or HCII activities could not be separated. Oligosaccharide mapping demonstrates that the concentration of an oligosaccharide comprising a portion of heparin's ATIII binding site in a particular heparin fraction correlates with ATIII mediated anti-IIa activity, but does not correlate with HCII mediated anti IIa activity. These results suggest that ATIII and HCII do not share a common binding site. Partial enzymatic depolymerization of heparin resulted in large oligosaccharides which could be purified and partially characterized. Although oligosaccharides of degree of polymerization (dp) 18 and 20 showed significant ATIII and HCII mediated anti-IIa activities no separation of these activities resulted. These data suggest however that a minimum chain length of dp18 was required for HCII mediated anti-IIa activity. PMID- 2922703 TI - Tyrosine platelet levels in normal subjects. PMID- 2922704 TI - PAF-induced platelet aggregation and TXB2 formation. PMID- 2922705 TI - Fibrinolytic activity of normal human blood monocytes. AB - Neutrophils (PMN) are important in the cellular phase of blood fibrino lytic activity (FA). The contribution of monocytes (MC), which have FA, is unclear. To determine the relative roles of these cells to activity in normal blood, we examined, by solid phase radiofibrin assay, FA of normal blood and plasma, and of purified PMN and MC, with and without plasminogen (PLG), mini-plasminogen (mPLG), the other major elastase fragment of PLG, or autologous plasma. PMN alone (0.5 x 10(6)/ml) had striking activity (292 +/- 25 SEM ng fibrin lysed/h; n = 10 normal subjects) while MC alone (0.5 x 10(6)/ml) had mean FA of 32 +/- 4 ng/h, which could be accounted for by contaminating PMN (36 +/- 8 ng/h). Thus, in a 1 h assay (when cellular FA accounts for 70-80% of FA in whole blood), normal numbers of MC (0.5 x 10(6)/ml) had no detectable FA when assayed with PLG or normal plasma. With longer assay times (2-6 h), PLG-dependent (plasminogen activator, PA) activity was demonstrated with mixtures of MC and PLG or plasma. This PA activity was released into the medium and required prior contact of MC and an intact, soluble PLG molecule for PA activity to be detected in medium (suggesting a PLG MC triggering mechanism), since activity was reduced or absent when MC were exposed to mPLG, the other major elastase fragment of PLG, or solid phase PLG. Exposure of MC to solid phase fibrin did not result in PA release. MC PA activity was little affected by cycloheximide pretreatment, indicating preformed rather than newly synthesized PA. By SDS-PAGE and fibrin zymography, MC extracts revealed a single PA band with features of pro-urokinase (single chain urinary type PA): Mr 55,000, inhibition by antiurokinase antibody (but not by anti-tPA), and resistance to inhibition by DFP. By ELISA assay, approximate normal monocyte content of this PA (as Mr 55,000 urokinase) was 0.03 fg (3.3 x 10(8) molecules) per cell. PMID- 2922706 TI - Is there any correlation between platelet aggregation, plasma lipoproteins, apoproteins and membrane fluidity of human blood platelets? AB - Fluorescence anisotropy (which is inversely related to membrane fluidity) of gel filtered platelets of 18 normolipemic subjects (20-26 years) was measured after incubation with three different fluorescent probes (DPH, TMA-DPH, and 6-As). These values were correlated to both platelet aggregation parameters after stimulation with ADP (4 microM), epinephrine (10 microM) or collagen (2 micrograms/ml PRP) and to plasma lipids, lipoproteins and apoproteins. Fluorescence anisotropy values after DPH-labeling of platelets were only negatively correlated to TG (p less than 0.05). No correlation was found between fluorescence anisotropy values of DPH, TMA-DPH and 6-As to LDL-C, Lp(a), HDL-C and HDL3-C (p less than 0.01). However, fluorescence anisotropy values of DPH and TMA-DPH were negatively correlated to apoproteins A2 and B (p less than 0.05). No correlations were found between fluorescence anisotropy after DPH labeling and different aggregation parameters. TMA-DPH and 6-As fluorescence anisotropy values are correlated to epinephrine induced stimulation (p less than 0.01). PMID- 2922707 TI - A microtitre plate test for assessment of in-vitro thrombogenicity in factor IX concentrates using a chromogenic substrate. PMID- 2922708 TI - A quantitative venous thrombosis model with stasis based on vascular lesion. PMID- 2922709 TI - Amiodarone potentiates acenocoumarin. PMID- 2922710 TI - In vivo effects of thymic epithelial culture supernate and thymosin fraction 5 on ADP-induced thromboembolic respiratory depression in mice. PMID- 2922711 TI - Active role of plasma in blood hypercoagulability induced by phenylhydrazine. PMID- 2922712 TI - [Regionalization of hospitals in Oslo]. PMID- 2922713 TI - [Is regionalization disadvantageous for patients? A registration study based on ambulance transports in Oslo]. AB - The number of transferrals between Oslo hospitals has been doubled since the hospital system was regionalized in 1982. Essentially, this development may be explained by the increased need to refer patients to the highly specialized hospitals because of recent years advances in medical technology. During a two month period in 1988, 4,841 admissions to hospitals in Oslo were registered, and 917 transferrals between hospitals. We found that patient-transport was adequate in 92% of the cases. However, ambulance personnel reported 389 cases (8%) of delayed admissions and unnecessary transferrals between the hospitals. In most cases, the real cause of the problems was a too rigid attitude among health workers. The inflexibility of the present system seems to be a major threat to the principle of regionalization. We propose a simple set of rules which will protect the principle and also the requests of the patients. PMID- 2922714 TI - [Has regionalization fulfilled administrative expectations? Work load, utilization and therapeutic costs at somatic hospitals in Oslo]. AB - Regionalization of the health system in Oslo has equalized pressure of work in the hospitals and improved utilization of available hospital beds. The Local Authorities have succeeded in restricting the increase in hospital costs through improved economic control. The study documents a considerable overcapacity of acute care beds and large differences between the hospitals in regard to waiting lists for surgical operations. Health care planners are recommended to give priority to the home care services and nursing homes, and at the same time reduce the number of acute care beds. PMID- 2922715 TI - [Regionalization in Oslo. Attitude of health personnel]. AB - A mail survey conducted among physicians, nurses and ambulance personnel in Oslo revealed considerable support for regionalization of the city's hospital services. The physicians would prefer to reduce the larger hospital regions and increase the smaller ones in order to improve collaboration between hospitals and other public health services. All health care workers strongly emphasized a need for a more flexible practice of the system with regard to regional boundaries. PMID- 2922716 TI - [Patient flow at a medical intensive care unit]. AB - Intensive care units have been established in all somatic hospitals in Norway over the last two decades. In order to examine the use of these units in a medical department the group of patients admitted to the unit at Haukeland hospital during a six month period was analyzed. The flow of patients is twice that found in the regular medical wards. The dominating reason for admittance is heart disease. The overall mortality of the patients in these units is high. However, it is probable that it may be possible to define groups of patients, who without reduction of medical security, could be treated in regular and less costly medical wards. PMID- 2922717 TI - [Smoking and sperm quality in men undergoing fertility studies]. AB - The sperm quality (sperm number, concentration, motility, morphology and vitality) of 350 men under fertility investigation were compared in relation to their smoking habits. No significant differences (Kruskal-Wallis test) in sperm quality could be demonstrated between non-smokers, moderate smokers (1-14 cigarettes/day) and heavy smokers (15-40 cigarettes/day). This was true when all the data were analyzed together and when analyzed separately for oligospermic/hypospermic men (1-39) or for men with reduced forward motility (less than 25% of sperm cells with progressive movement). The distribution of non smokers, moderate and heavy smokers was the same in groups of men with normal sperm quality as in groups with reduced quality. The present study does not provide support for the contention that smoking has deleterious effects on sperm quality, at least when using conventional parameters. PMID- 2922718 TI - [Splenic salvage in distal pancreatectomy]. AB - In distal pancreatectomy, splenectomy has usually been an expedient component. In view of the recognized risk of overwhelming postsplenectomy septicaemia the current trend is splenic salvage whenever possible, in trauma surgery as well as in elective surgery. In order to emphasise this point we report a case of distal pancreatectomy with splenic salvage. PMID- 2922719 TI - [Gelastic and cursive epilepsy]. AB - When the most prominent ictal symptom in an epileptic seizure is laughing or running the condition has been termed respectively gelastic or cursive epilepsy. The article presents five patients with these ictal symptoms and discusses their clinical and EEG-features, etiology, and localisation of lesions responsible for the seizures. Laughter and running as ictal symptoms are usually part of complex partial seizures involving limbic structures or their efferent or afferent pathways. PMID- 2922720 TI - [Pulmonary edema and pericarditis after inhalation of Teflon fumes]. AB - Inhalation of fumes from pyrolysis of polytetrafluoroethylene (Teflon) is known to cause polymer fume fever, a mild syndrome of influenza-like symptoms of short duration. Occasionally more severe reactions occur. Several cases of pulmonary edema have been reported, only one of which was fatal. We report a case history of pulmonary edema and pericarditis following inhalation of fumes from grinding a Teflon coated surface. Pericarditis has not been reported previously in connection with polymer fume reactions. We discuss various aspects of such reactions, with reference to the case and to selected literature. PMID- 2922721 TI - [Dietary advice in hyperlipidemia. A challenge for the health care service]. AB - We propose practical dietary advice for patients with hyperlipidemias, based on data obtained from new results in epidemiology, clinical trials and laboratory experiments. We suggest a schedule for obtaining reliable data on dietary habits, to be used as a basis for advice to the individual patient. If the dietary fat intake can be reduced from about 40% to 25% of the total energy it is possible to achieve an average reduction in serum cholesterol of 10-20%. It is very important that doctors and other health personnel become involved in providing dietary advice in connection with treatment and prevention of coronary heart disease. PMID- 2922722 TI - [Radial artery flap]. AB - We have successfully treated patients suffering from skin and soft tissue defect with arteria radialis forearm flap. We have used this method either with proximally or distally vascular pedicled island flap. On several occasions we used forearm flap as a free microvascular transplant. Sensation can be provided through anastomosis of one of the sensitive nerves of the forearm and, if necessary, pedicled or free osteocutaneous flap can be carried out. PMID- 2922724 TI - [Use of beds in somatic hospitals in Oslo in 1986]. AB - There are more hospital beds available in somatic hospitals in Oslo than in any other county in Norway. Nevertheless, the number of patients discharged from Oslo hospitals is not substantially higher than expected when we consider the demographic composition of the region. The beds in Oslo hospitals are allocated three times more often than hospital beds in other parts of the country to elderly patients needing nursing. Thus the Oslo hospitals seem to take over functions which are normally taken care of elsewhere in Norway at lower levels of treatment. As a result, the annual number of discharged patients per bed is lower in Oslo hospitals than in corresponding Norwegian hospitals elsewhere. PMID- 2922723 TI - [Correct handling of serum separating gel tubes is of significance]. AB - We review the construction, handling, advantages and drawbacks of serum separator tubes. A study is reported, which demonstrates that serum potassium measurements are less reliable when gel-barrier sampling tubes are used incorrectly. We give guidelines for correct use of such equipment. PMID- 2922725 TI - [Attitudes of the population and patients to regionalization in Oslo]. AB - A representative sample of the population of Oslo was interviewed, and a sample of patients discharged from Oslo-hospitals were surveyed using a standardized questionnaire which focused on their attitudes towards the regionalization of the health services in Oslo. The results clearly demonstrate that the patients and the population at large both have full confidence in Oslo's hospitals. In general, the patients felt secure that their regional hospital had both the capacity and expertise to take proper care of them. Only a small minority would have changed hospital if this had been possible. The majority were in favour of the present regionalization principle, and prefer this to an arrangement where they could choose a hospital themselves. PMID- 2922727 TI - [A student who came from the reading room]. PMID- 2922726 TI - [Should hospitals be allowed to transfer surplus patients? A study of the patient load situation at medical and surgical wards in regionalized hospitals in Oslo]. AB - The regionalization arrangements in Oslo are based on each regional hospital having a clearly defined geographical catchment area. This paper considers the patient load in these four regional hospitals during the course of a year and discusses whether a cooperative arrangement should be introduced so that overloaded hospitals are permitted to transfer surplus patients to other hospitals. This arrangement is not considered advisable for the following reasons: Firstly, there is rarely enough space; secondly, peak loads usually occur at the same time; and finally, such an arrangement would tend to undermine the advantages of each regional hospital having its own defined sphere of responsibility. PMID- 2922728 TI - [Spigelian hernia alias inguinal hernia]. PMID- 2922729 TI - [Pregnancy and sick leave]. PMID- 2922730 TI - [Heart contusion]. PMID- 2922731 TI - [Hearing impairment in Oslo children]. PMID- 2922732 TI - [Hearing loss among children in Oslo]. AB - The study concerns children born the years 1975-84. Only children in need of hearing aids are taken into account. The incidense was 1.08 per 1,000 live born children. The prevalens in January 1988 was 1.57 per 1,000 children, including 18 children moving into the city. The etiology among 75 children was 47% prenatal, 16% perinatal, 11% postnatal defects and further 26% of unknown neurogenic origin. Among the 63 impaired children living in Oslo 1988 15 or 24% had multiple handicaps. Identification of hearing loss before one year of age increased from 23% for children born 1975/79 to near 60% for children born 1980/84. At risk children should be tested before leaving hospital after delivery. PMID- 2922733 TI - [Memory function after head injuries]. AB - The article evaluates memory function in 190 patients with traumatic head injuries. Both the patient's own impression of his/her memory function and a neuropsychological examination are separately rated as normal, slight, moderate or severely affected. The main tendency is for patients with mild head injuries (who were never in coma or who were in coma for up to 15 minutes) to express greater problems with their memory function than revealed by neuropsychological testing. On the other hand, patients who were in coma for more than one week, express memory problems less frequently than shown by testing. There are low corresponding figures between the different degrees of memory function expressed by the patients, and the results of the neuropsychological testing. The results have implications both for diagnosis and for vocational counseling. PMID- 2922734 TI - [Improved aerobic exercise performance after short-term training of patients with coronary disease]. AB - Maximal oxygen consumption was measured during treadmill exercise in 44 patients with coronary artery disease. Exercise was performed before and after a 4-week course of training. Patients with a previous myocardial infarction and no angina pectoris (n = 27) increased their maximal oxygen consumption by 16% after training. There was no such increase in patients with angina pectoris (n = 17). The subjective feeling of wellbeing after training was the same in both groups of patients. Thus, the advantages of short term training can be both of a symptomatic character and a real improvement in cardiovascular function. PMID- 2922736 TI - [Neuroleptic malignant syndrome]. AB - Neuroleptic malignant syndrome is a rare but often serious complication of treatment with antipsychotic drugs. The syndrome is characterized by hyperthermia, altered state of consciousness, muscular rigidity and autonomous dysfunction. The article reviews the syndrome and presents a case-history. PMID- 2922735 TI - [Fatal infection after a dog bite. Septicemia caused by Dysgonic fermenter 2 bacteria]. AB - The article describes a case of lethal septicaemia caused by the bacterium Dysgonic fermenter 2, following a dog bite. We discuss symptoms, bacteriology and treatment, and present a review of the literature. PMID- 2922737 TI - [Intestinal spirochaetosis]. AB - It is well known that spirochetes may be found in the digestive tract of various species, including humans. We describe a homosexual man with long-standing diarrhoea, probably caused by intestinal spirochaetosis. The diagnosis was based upon light microscopic demonstration of a thin haematoxyphilic bandlike layer covering the intestinal surface epithelium, which is an established diagnostic characteristic of intestinal spirochaetosis. The spirochaetosis was further confirmed by electron microscopy. The pathogenetic significance of spirochetes in human intestinal disease is not fully understood. However, intestinal spirochaetosis should be suspected in patients with long-standing diarrhoea. Symptomatic spirochaetosis in the gut responds well to treatment with metronidazole. The spirochetes of the human digestive tract constitute a newly defined genus of the family Treponemataceae. PMID- 2922738 TI - [Computer systems for general practitioners. Status and development]. AB - Patient-administrative systems are becoming increasingly accepted in general practice. The market is now more mature than before. Many physicians are now purchasing computer systems for general practice the second time. Due to national characteristics of the health services the market for these systems is not truly international. In Norway this market is dominated by two makes: Infodoc and Profdoc. In future more physicians will use systems for general practice, and more functions will be added, although the usefulness of these may be a matter for discussion. Furthermore, the importance of telecommunications is expected to increase, and similarly, integration with other services. This development would be furthered by central government action for the purpose of harmonizing and standardizing data, systems and possibly user-interface. PMID- 2922739 TI - [Cardiovascular diseases as a public health problem]. PMID- 2922740 TI - [Technical aids. A better life for terminal cancer patients]. PMID- 2922741 TI - [Electronic information bank for health services in Norway]. AB - This article proposes the establishment of a central, on-line information bank for the Norwegian health services. The article discusses the potential content and functions of the information bank. It is concluded that, in addition to increasing the availability of health-related information, such an information bank might also improve communication at several levels of the health care system. PMID- 2922742 TI - [What does the public think about the regional health care? A questionnaire study done in Northern Norway]. PMID- 2922743 TI - [Synonymous preparations and drug costs. A debate which has gone wrong?]. PMID- 2922744 TI - [The occurrence of hardjo-positive dairy cows in the Northern Netherlands. A prospective serological survey]. AB - More than 5000 lactating cows from 82 farms, in the northern part of the Netherlands, were serologically examined for antibodies to Leptospira hardjo. Hardjo-positive cows were found on 52% of the farms with a mean incidence of 23% positive animals. Considerable differences were observed in the percentages hardjo-positive cows per region (7-30%), as well as in the percentages positive cows per positive farm (22-46%). With the exception of one region (14%) the percentages of hardjo-positive farms per region hardly differed (average 58%). In addition to the animal survey 488 sera of men working and/or living on cattle farms were also examined. Twenty-six persons were hardjo-positive. Most of these persons (circa 90%) milked regularly. All seropositive persons were found on farms with hardjo-positive cattle. Results from an inquiry on circa 200 farms indicated, that hardjo-infections probably occur with a higher frequency on larger farms. Finally the results from this survey confirm the observation in the literature, that symptoms of hardjo-infections are more frequently found in the autumn. PMID- 2922745 TI - [Feline immunodeficiency virus (FIV)]. PMID- 2922746 TI - [Blood coagulation-promoting agents: which ones, when, why?]. PMID- 2922747 TI - [Dehorning of calves using the Leister-Ghibli hot air pistol]. AB - The present study was concerned with the applicability and efficiency of the Leister-Ghibli hot-air gun used in disbudding calves. The tool was used in thirty three calves averaging an age of seven weeks. Subsequently, none of the calves showed growth of horns. When the burning time is 20-25 seconds, the depth effect of the hot air is mainly limited to the epidermis and, at the same time, suffices to prevent the growth of horn. PMID- 2922749 TI - "How to write a paper". PMID- 2922748 TI - [Breed variations in feed intake and energy utilization in dairy cows]. AB - In four experimental studies on feed intake, two completely mixed rations containing 0 and 50 per cent of concentrates respectively were fed ad lib. to dairy cattle of four different breeds: the Jersey, the Holstein-Friesian (HF), the Dutch Black-and-White (FH) and the Dutch Red-and-White (Meuse-Rhine-Yssel). There are considerable differences in feed intake between the breeds, particularly between the Jerseys and the heavier breeds (HF + MRY + FH). The experimental studies in the Jerseys showed that there was an interaction between breed and the composition of the feed, which is due to differences in nutrient requirements between breeds. These variations are attributable to differences in composition of the milk. The dairy breeds, Jersey and HF, use a large part of the energy taken up for milk production and a smaller part for maintenance than do the double-purpose breeds: FH and MRY. PMID- 2922750 TI - Cardiogenic shock after acute coronary occlusion. Pathogenesis, early diagnosis, and treatment. AB - The early natural history of left anterior descending coronary artery (LAD) occlusion and the development of cardiogenic shock was studied in 35 open chest anesthetized dogs observed for 6 hours. Six control dogs underwent LAD isolation without occlusion, 13 underwent isolated LAD occlusion to simulate single vessel disease, and 14 underwent LAD occlusion and a 50% left circumflex coronary artery (LCA) stenosis to stimulate multi-vessel disease. Control dogs undergoing anesthesia showed no significant changes in hemodynamics after 6 hours. All dogs with single vessel disease survived and developed immediate and persistent dyskinesis of the anterior wall, a compensatory hypercontractility of remote muscle (131% of control)*, slight energy and substrate depletion and anaerobic metabolism (increased G6P)* despite maintenance of "normal" blood flow through the LCA. In contrast, early mortality was 57% in simulated multi-vessel disease as intractable ventricular fibrillation and/or cardiogenic shock caused the deaths of 7 of 13 dogs (57%)*. Remote muscle became progressively hypocontractile (61% of control)* and caused progressive reduction in stroke work index (less than or equal to 0.5 g x m/kg)*. Remote muscle showed moderate substrate and energy depletion (greater than or equal to 60% fall of ATP and CP, 37% fall of glutamate)* and more pronounced evidence of anaerobic metabolism (G6P rose 373%)* despite "normal" blood flow. These findings suggest that remote muscle is the principle determinant of mortality after an otherwise non-lethal cardiac event.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2922751 TI - Valve replacement in children: early and late results. AB - In order to analyze the problems associated with prosthetic valve replacement (PVR) in the pediatric population, we have reviewed 29 children, 3.5 to 15 years of age, who were operated upon from 1970 to 1986. The indications were congenital valve malformations in 16 patients, rheumatic valve disease in 7, degenerative disease in 2 and bacterial endocarditis in 4. Ten children underwent aortic valve replacement (AVR), 14 mitral valve replacement (MVR), 1 tricuspid valve replacement and 4 double valve replacement (mitral-aortic in 3 and mitral tricuspid in 1). Twenty-one mechanical (11 aortic and 10 mitral) and 12 biological prostheses (8 mitral, 2 aortic, and 2 tricuspid) were implanted. There was 1 hospital death (3.4%). Follow-up data were available for all survivors from 3 to 184 months. There were 8 late deaths (5.9% patient-year), 4 among children with mechanical and 4 among those with biological prostheses. Overall actuarial survival at 14 years is 62.5 +/- 10.2% with no significant difference in survival between AVR (77.8 +/- 14%) and MVR (44.4 +/- 16%) (p = 0.31) at 10 years and between recipients of mechanical (65.7 +/- 13%) or biological prostheses (60.0 +/ 15%) (p = 0.62) at 6 years. No documented embolic or anticoagulant-related complications occurred in the entire series.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2922752 TI - Lethal blockage of a Bjork-Shiley artificial heart valve caused by strut fracture -the metallurgical aspect. AB - The fracture of the outlet strut of a Bjork-Shiley artificial heart valve implanted in a 21 year old man lead--6 years after the operation--to the valve disc jamming closed with a resulting lethal heart failure and circulation standstill. The probable cause of the valve strut fracture could be determined by metallurgical/metallographical investigation of the material and the production methods. PMID- 2922753 TI - Translocation of aberrant right subclavian artery in dysphagia lusoria in children through a right thoracotomy. AB - Anatomical reestablishment of orthograde flow into the right subclavian artery in children with arteria lusoria is emphasized. We present two infants and one young child who were successfully treated by translocation of the aberrant right subclavian artery to the ascending aorta without graft interposition through a right thoracotomy. Several surgical approaches are reviewed. PMID- 2922754 TI - Is electrocautery safe for internal mammary artery (IMA) mobilization? A study using scanning electron microscopy (SEM). AB - Being the graft of choice, the internal mammary artery (IMA) is increasingly used for coronary artery bypass grafting. Presently, electrocautery is liberally used to mobilize both IMAs. Preservation of IMA flow surface was evaluated by scanning electron microscopy (SEM) after mobilization with either sharp dissection or electrocautery in five clinical patients undergoing coronary artery bypass surgery. Major side branches were secured with metallic clips. Specimens for SEM were harvested after heparinization but before institution of cardiopulmonary bypass from the terminal branches of both IMAs after they had been skeletonized with either mobilization method. When mobilization of the IMA was performed as a pedicle, the flow surface was well preserved in both groups. However, if a contact of the electrocautery blade with the wall of the IMA or with a metallic clip parallell to the wall was allowed, a clearly visible zone of endothelial damage, sometimes associated with mural trombus formation was observed. In conclusion, caution is needed with electrocautery. Thermal injuries of the IMA may remain undetected during surgery and cause graft occlusion later. PMID- 2922755 TI - Bierhoff et al. 'Hemangiopericytoma of the lung--a rare differential diagnosis of lung tumors'. PMID- 2922756 TI - In vitro metabolism of methylene chloride in human and animal tissues: use in physiologically based pharmacokinetic models. AB - Physiologically based pharmacokinetic (PB-PK) models describe the dynamic behavior of chemicals and their metabolites in individual tissues of living animals. Because PB-PK models contain specific parameters related to the physiological and biochemical properties of different species as well as the physical chemical characteristics of individual chemicals, they are useful tools for performing high dose/low dose, dose route, and interspecies extrapolations in hazard evaluations. An example of such extrapolation has been presented by M. E. Andersen, H. J. Clewell III, M. L. Gargas, F. A. Smith, and R. H. Reitz (Toxicol. Appl. Pharmacol. 87, 185-205, 1987), who employed a PB-PK model for methylene chloride (CH2Cl2) to estimate the chronic toxicity of this material. However, one limitation of this PB-PK model was that the metabolic rate constants for the glutathione-S-transferase (GST) pathway in humans were estimated by allometric scaling rather than from experimental data. In this paper we report studies designed to estimate the in vivo rates of metabolism of CH2Cl2 from in vitro incubations of lung and liver tissues from B6C3F1 mice, F344 rats, Syrian Golden hamsters, and humans. A procedure for calculating in vivo metabolic rate constants from the in vitro studies is presented. This procedure was validated by making extrapolations with mixed function oxidase enzymes (MFO) acting on CH2Cl2, where both in vitro and in vivo rates of metabolism are known. The in vitro rate constants for the two enzyme systems are consistent with the hypothesis presented by Andersen et al. that metabolism of CH2Cl2 occurs in vivo by two competing pathways: a high-affinity saturable pathway (identified as MFO) and a low affinity first-order pathway (identified as GST). The metabolic rate constants for GST obtained from these studies are also consistent with the hypothesis of Andersen et al. that production of large quantities of glutathione/CH2Cl2 conjugates in vivo may increase the frequency with which lung and liver tumors develop in some species of animals (e.g., B6C3F1 mouse). When in vivo studies in humans are unavailable, in vitro enzyme assays provide a reasonable method for estimating metabolic rate constants. PMID- 2922757 TI - Histochemical localization of rhodanese activity in rat liver and skeletal muscle. AB - A previously described histochemical technique was applied to the localization of rhodanese (thiosulfate sulfurtransferase, EC 2.8.1.1) activity in rat skeletal muscle and liver. The physiological function of rhodanese is controversial, but it and other sulfurtransferases can catalyze the conversion of cyanide to the much less toxic thiocyanate. The volume of distribution of cyanide in human and dog is said to correspond roughly to the blood volume. Because of this and other observations, it was hypothesized that sulfurtransferase activity associated with the vascular endothelium on smooth muscle layers of blood vessels might play a role in cyanide detoxification. However, little enzyme activity as identified histochemically was associated with those sites in comparison with others examined. As expected, high activity was found in the liver and moderately high levels were present in skeletal muscle. In muscles sectioned longitudinally, points of rhodanese staining occurred in linear arrays along the lengths of the muscle fiber corresponding to the location of mitochondria within the fiber. The original technique called for incubation of tissue sections with both thiosulfate and cyanide. When thiosulfate was omitted, staining for rhodanese activity was still clearly identifiable in both liver and muscle sections with cyanide alone. In muscle sections the inclusion of both thiosulfate and cyanide resulted in a preferential staining of type I fibers presumably because of their higher content of mitochondria. Thus, this technique is a potential alternative to the NADH dehydrogenase stain for distinguishing between type I and type II muscle fibers. Incubation of tissue sections with only thiosulfate produced results that did not appear to differ from those obtained when both substrates were omitted. From these observations it may be inferred that the endogenous pool of sulfane-sulfur available to sulfurtransferases is larger than any alleged endogenous pool of cyanide. Although sulfurtransferase activity in muscle appeared to be lower than that in liver, the total body muscle mass is greater than the liver mass. Thus, these results support other evidence that skeletal muscle may make a significant contribution to total cyanide biotransformation in the absence of exogenously added thiosulfate. PMID- 2922758 TI - Effects of subacute administration of physostigmine on blood acetylcholinesterase activity, motor performance, and soman intoxication. AB - Subacute administration of carbamates is under study as pretreatment against soman, a toxic anticholinesterase agent. In this study, the sustained release of physostigmine salicylate (Phy) in rats was achieved via osmotic minipumps; each pump contained 2 ml of Phy solution (0.4, 10, or 50 mg/ml) and delivered 2.5 microliter/hr for 28 days. At the corresponding dosage rates, rat whole blood acetylcholinesterase (AChE) activity was suppressed by approximately 11, 42, and 66%, respectively. These levels of Phy administration caused no decrement in performance on an accelerating rotarod (ARR) when tested between Days 3 and 27 of the 28-day exposure. The highest level of Phy caused a mean weight loss of 11% initially, with recovery by the 17th day. On Day 27 the rats were given 0.08 mg/kg, im, of scopolamine (SCP), 30 min before exposure to soman (58 micrograms/kg; 1 LD50, iv). In combination with SCP, the two highest levels of Phy prevented lethality and a decrement in ARR performance by soman, while the lowest level showed 40% lethality after soman and the survivors exhibited partial recovery to their own presoman control performance by 24 hr. These results suggest that, in a pretreatment mode, 42-66% inhibition of AChE by sustained exposure to Phy, with an acute dose of cholinolytic, would suffice to protect against lethality and motor performance decrement by a toxic level of soman. PMID- 2922759 TI - Modulation of neurotoxic esterase activity in vitro by phospholipids. AB - Neurotoxic esterase (NTE), the proposed molecular site for the initiation of organophosphorus-induced delayed neuropathy, is a membrane-associated enzyme. NTE activity was solubilized from chicken brain microsomal membranes with the detergent 3-[(3-cholamidopropyl)dimethylammonio]-1- propanesulfonate and partially separated from other solubilized hen brain esterases by DEAE-Sephacel anion-exchange chromatography using stepwise increases in salt concentration; however, there was poor recovery of NTE activity and only a slight increase in NTE specific activity. NTE activity in the "high salt" fraction (i.e., the NTE enriched fraction) was markedly activated by a heat-stable factor(s) present in other fractions eluted from the column. This activating factor was extracted with organic solvents, suggesting that it may be lipid. In a related study, purified phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine were also found to activate the partially separated NTE activity in a concentration dependent manner while phosphatidyl-inositol was found to inhibit the same partially separated NTE fraction in a concentration-dependent manner. The results suggest that lipids may modulate NTE activity and that the loss of lipid cofactors during chromatographic separations may underlie some of the difficulties encountered in isolation of active NTE. PMID- 2922760 TI - Effects of adsorption of benzo[a]pyrene onto carbon black particles on levels of DNA adducts in lungs of rats exposed by inhalation. AB - Exposure of rodents to benzo[a]pyrene (BaP) associated with particles has previously been shown to result in increased retention of BaP and metabolites in lungs. To determine if DNA damage might be enhanced, DNA adducts were measured in lungs of F344 rats following inhalation of pure BaP aerosols or BaP absorbed on carbon black particles. Groups of rats were exposed nose only to filtered air, [14C]BaP (2 mg/m3), or [14C]BaP (2 mg/m3) adsorbed on carbon black (97 mg/m3) (BaP/CB) for 4 hr/day, 1 day/week, for 12 weeks. Groups of rats were terminated at 4, 8, 12, 16, 20, and 24 weeks after the beginning of the 12-week exposure period. Retention of total 14C in lungs was used as an indicator of total reactive metabolites. DNA isolated from lungs was analyzed for adducts using a 32P-postlabeling assay. Inhalation of BaP/CB resulted in 100-fold higher levels of 14C in lungs at the end of the 12-week exposure than did inhalation of pure BaP. The halftime for the decline in 14C levels was 34 +/- 3 weeks (mean +/- SE) for rats exposed to BaP/CB and 6 +/- 2 weeks for rats exposed to pure BaP. At the end of 12 weeks of exposure, DNA adducts in lungs of rats exposed to pure BaP ranged from 2-15 adducts per 10(9) bases (mean = 7, n = 4) and in rats exposed to pure BaP absorbed on carbon black ranged from 10-12 adducts per 10(9) bases (mean = 11, n = 4); DNA adducts in lungs of sham-exposed rats ranged from 0-2 adducts per 10(9) bases (mean = 1, n = 4). The halftimes for the decline in DNA adducts in lungs were 3 +/- 1 weeks (mean +/- SE) for the rats exposed to BaP/CB and 5 +/ 2 weeks for the rats exposed to BaP. One of the DNA adducts found following exposure to both BaP and BaP/CB was tentatively identified as the BaP diol epoxide deoxyguanosine (BPDE) adduct. Levels of both total and BPDE DNA adducts were significantly increased (p less than 0.05) in lungs of rats exposed to both BaP and BaP/CB compared to levels in lungs of sham-exposed rats. There were no significant differences in levels of DNA adducts in lungs of rats exposed to BaP or BaP/CB, although the pattern of adducts was different between the two exposure modes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2922761 TI - Retinoid-induced hemorrhaging and bone toxicity in rats fed diets deficient in vitamin K. AB - The recent increase in the clinical use of synthetic vitamin A compounds has led to concern of possible side effects. Some of these effects are known to be influenced by dietary levels of vitamin K. We therefore compared the toxic effects of 13-cis-retinoic acid (13cisRA), retinyl acetate (ROAc), and N-(4 hydroxyphenyl)retinamide (4HPR) in male Sprague-Dawley rats maintained on diets containing different levels of vitamin K. Animals were fed either an NIH-07 diet supplemented with menadione (3.1 ppm vitamin K3), an NIH-07 diet not supplemented with menadione, or an AIN-076 purified diet devoid of vitamin K. The retinoids had no effect on prothrombin times of animals fed the supplemented diet. When menadione was omitted from the diet, however, 4HPR-dosed animals had elevated prothrombin times. This effect was observed as early as Day 7 and was accompanied by one confirmed hemorrhagic death. 13cisRA-dosed animals showed no change in prothrombin times. In the high-dose ROAc group, there was a twofold increase in prothrombin times but only after prolonged dosing. In animals fed the NIH-07 diets, 13cisRA and ROAc induced multiple bone fractures at all dose levels. In contrast, 4HPR administered at the highest dose induced only one fracture in one animal. Animals fed the purified diet lost weight faster and diet sooner than those maintained on the other diets. Bone fractures were not observed in these animals because of early deaths resulting from hemorrhaging. For all retinoid dosed groups maintained on the purified diet, changes in prothrombin times occured as early as 1 week. The order of effect was 4HPR greater than ROAc greater than 13cisRA, with increases in prothrombin times correlating with increases in hemorrhagic deaths. Hence, the degree of retinoid-induced hemorrhage, but not the incidence of bone fractures, was inversely related to vitamin K levels in the diet. 13cisRA and ROAc, but not 4HPR, caused a dose dependent reduction in plasma osteocalcin, an effect that correlated with retinoid-induced bone effects. In contrast, serum alkaline phosphatase was elevated in animals dosed with 13cisRA or 4HPR but not in those dose with ROAc. For this enzyme, the electrophoretic pattern on agarose gel showed a decrease, compared to controls, in the major isozyme in serum of ROAc-dosed animals. Hence, plasma osteocalcin is a better predictor of retinoid-induced bone effects than serum alkaline phosphatase. PMID- 2922762 TI - Studies on the mechanism of coumarin-induced toxicity in rat hepatocytes: comparison with dihydrocoumarin and other coumarin metabolites. AB - Single doses of coumarin (125 mg/kg, ip) produced a depletion of hepatic nonprotein sulfhydryl groups (mainly reduced glutathione; GSH) in young male Sprague-Dawley rats after 2 hr and increased liver weight and produced hepatic centrilobular necrosis after 24 hr. Coumarin also produced time- and dose dependent toxic effects in primary rat hepatocyte cultures. A marked reduction of GSH levels was also observed in vitro and this was not due either to the formation of oxidized glutathione (GSSG) or to the leakage of GSH and/or GSSG from the hepatocytes. Coumarin-induced toxicity in rat hepatocytes could be inhibited by the cytochrome P450 inhibitors ellipticine and metyrapone and potentiated by depleting hepatocyte GSH levels with diethyl maleate. In contrast to coumarin, dihydrocoumarin--which lacks the 3,4-double bond--produced little toxicity in rat hepatocytes either in vivo (127 and 254 mg/kg, ip) or in vitro. Similarly, coumarin was more toxic to rat hepatocytes than a number of known coumarin metabolites including 3- and 7-hydroxycoumarin and o-hydroxyphenylacetic acid. The results of these studies demonstrate a good in vivo/in vitro correlation for the effects of coumarin and dihydrocoumarin in rat hepatocytes. Furthermore, the data suggest that coumarin hepatoxicity in the rat is due to coumarin bioactivation by cytochrome P450-dependent enzymes to a toxic metabolite(s), which may be a coumarin 3,4-epoxide intermediate. GSH appears to protect against coumarin-induced toxicity possibly by the formation of conjugates with the toxic coumarin metabolite(s). PMID- 2922763 TI - The isolated perfused porcine skin flap. III. Percutaneous absorption pharmacokinetics of organophosphates, steroids, benzoic acid, and caffeine. AB - The isolated perfused porcine skin flap (IPPSF) has been developed as an alternative in vitro tool for examining the pharmacokinetics and mechanisms of percutaneous absorption. In this study, dosing solutions of seven 14C radiolabeled compounds representing three chemical classes--organic acid/base [benzoic acid (B), caffeine (C)], organophosphate (OP) pesticides (diisopropylfluorophosphidate, malathion, parathion), and steroid hormones (progesterone, testosterone)--were prepared in ethanol and applied topically at a surface concentration of 40 micrograms cm-2 to the IPPSF. A three-compartment pharmacokinetic model used to stimulate mass transfer from the surface (C1), diffusion through epidermis and dermis (C2), and transfer into the capillary perfusate (C3), was developed based on flux through the IPPSF from 0 to 8 hr. This basic model accurately stimulated measured IPPSF fluxes for five of seven compounds, including the OPs and steroids. The model was modified to simulate the shunting of drug to fast and slow release pathways, which occurred for B 3-4 hr postapplication, and to account for flow-dependent flux increases seen for C at 6 hr postapplication. The latter may be due to a direct pharmacologic effect, since C is a known vasodilator. Extrapolated (to 6 days) areas under the curve from the model simulations were compared with in vivo percutaneous absorption estimates, obtained from 6-day excretion studies in pigs. The in vivo-in vitro correlation, based on simple linear regression across compounds, was excellent (R2 = 0.88, R = 0.94, p less than 0.002). These results suggest that xenobiotic penetration in the 8-hr IPPSF experiments is highly predictive of in vivo absorption totals (6 day studies). In addition, since pig and human skin are similar physiologically and pharmacologically, the IPPSF may eventually have applications in formulating human dermal risk assessment models. PMID- 2922764 TI - Studies of chemical toxicity to fresh and cryopreserved rat hepatocytes. AB - Isolated hepatocytes are useful for studying the metabolism and mechanisms of hepatic toxicity of foreign chemicals. A problem with using human hepatocytes is the limited and irregular availability of normal human liver. Cryopreservation could provide a useful way of storing hepatocytes until they are needed. As a preliminary step to using human hepatocytes we have compared the toxic response to chemical toxicants of primary cultures of fresh rat hepatocytes and rat hepatocytes cryopreserved as previously described (G. Powis, K. S. Santone, D. C. Melder, L. Thomas, D. J. Moore, and T. J. Wilke, 1987. Drug Metab. Dispos. 15, 826). After 24 hr in culture the cryopreserved hepatocytes had a plating efficiency 75% that of noncryopreserved hepatocytes. The cultured cryopreserved hepatocytes showed a small increase in spontaneous lactate dehydrogenase release compared to that of cultured noncryopreserved hepatocytes. A similar toxic chemical-induced increase in lactate dehydrogenase release occurred in the cultured cryopreserved as in the noncryopreserved hepatocytes. The 50% effective concentrations (EC50) for lactate dehydrogenase release (+/- SE, n = 3 preparations) from cultured cryopreserved and noncryopreserved hepatocytes for chlorpromazine were 235 +/- 20 and 215 +/- 30 microM, for cadmium chloride 200 +/ 5 and 272 +/- 23 microM, and for menadione (2-methyl-1,4-naphthoquinone) 24 +/- 7 and 44 +/- 8 microM, respectively. The EC50 values for intracellular glutathione depletion in cultured cryopreserved and noncryopreserved hepatocytes were for chlorpromazine 200 +/- 8 and 235 +/- 8 microM, for cadmium chloride 242 +/- 19 and 213 +/- 7 microM, and for menadione 22 +/- 2 and 21 +/- 3 microM, respectively. The results show that cryopreservation offers a practical way of storing rat hepatocytes for studies of chemical toxicity. PMID- 2922765 TI - Drug-induced hydrogen peroxide production in isolated rat hepatocytes. AB - A method for measuring drug-induced hydrogen peroxide production in freshly isolated rat hepatocytes is described. 3-Amino-1,2,4-triazole, an irreversible inhibitor of the enzyme catalase markedly reduces the capacity of isolated hepatocytes to metabolize hydrogen peroxide, with maximum inhibition (80%) being observed after 40 min of co-incubation. The present method is based on the observation that this inhibition of catalase by 3-amino-1,2,4-triazole is prevented by methanol and that the effect of methanol is reversed in the presence of hydrogen peroxide. Using this assay we could demonstrate increased hydrogen peroxide production during the metabolism of diquat, paraquat, xanthine, benzylamine and glycolate by hepatocytes. Inhibition of the hydrogen peroxide metabolic capacity was greatest with glycolate and diquat, whereas paraquat and benzylamine only had a minor effect. PMID- 2922766 TI - 6-Methyl-1,3,8-trichlorodibenzofuran (MCDF) as a 2,3,7,8-tetrachlorodibenzo-p dioxin antagonist in C57BL/6 mice. AB - 6-Methyl-1,3,8-trichlorodibenzofuran (MCDF), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and TCDD plus MCDF were administered to C57BL/6 mice and their effects on several aryl hydrocarbon (Ah) receptor-mediated responses including hepatic microsomal aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD) induction, immunotoxicity and teratogenicity were determined. MCDF did not induce hepatic microsomal AHH and EROD at doses up to 500 mumol/kg, however, co administration of MCDF (50 mumol/kg) with a dose of TCDD which elicited a submaximal induction response (i.e. ED80-100, 15 nmol/kg) resulted in some small but significant inhibition of the induction of hepatic microsomal AHH and EROD (14 and 17%, respectively) compared to that observed with TCDD alone. Co administration of TCDD and other doses of MCDF (10, 100, 200 or 500 mumol/kg) did not effect the induction response. These results were in contrast to the effectiveness of MCDF as an antagonist of the induction of AHH and EROD by TCDD in the rat (up to 50% inhibition of monooxygenase induction). Administration of MCDF (4, 20 and 40 mumol/kg) to C57BL/6 mice caused some inhibition of the splenic plaque-forming cell response to sheep erythrocytes only at the highest dose (26% decrease); the interaction of MCDF (4, 20 and 40 mumol/kg) and an immunotoxic dose of TCDD (3.7 nmol/kg) resulted in significant protection from the immunotoxic effects of TCDD at the 2 higher dose levels of MCDF. Similarly, MCDF (400 mumol/kg) did not cause cleft palate in mice but at this dose level MCDF afforded some protection from TCDD (20 micrograms/kg)-mediated cleft palate in mice. However, studies utilizing [3H]TCDD suggested that the protective effects may be due to modulation of TCDD reaching the palate in the co-treated animals (MCDF plus TCDD). Although both MCDF and Aroclor 1254 were both weak Ah receptor agonists in C57BL/6 mice, the former compound was much less effective as a TCDD antagonist. The observed species-specific effects for these 2 TCDD antagonists may be related species-dependent differences in receptor structure and receptor-ligand (i.e. agonist or antagonist) interactions. PMID- 2922767 TI - Sex differences in nephrotoxic and gastrointestinal effects of phenylbutazone. AB - Male and female Wistar rats were used to study the sex differences in nephrotoxic, ulcerogenic and lethal effects of phenylbutazone (PBZ). In one series of experiments, male and female rats were given daily oral doses of 25, 125, 250, 400 and 500 mg PBZ/kg for 7 days to assess mortality, gross and microscopic lesions of the stomach, intestine and kidneys and to determine the PBZ effects on renal protein and glucose excretion. In another series of experiments, PBZ effects on renal gluconeogenesis and p-aminohippurate (PAH) accumulation in renal cortical slices were measured 12 h after administration of the same PBZ doses to male and female rats. Reduced glutathione (GSH) depletion and malondialdehyde (MDA) content in kidney cortex and liver were determined 2 h after a single administration of 250 mg PBZ/kg to male and female rats. To measure the effects of PBZ on blood urea nitrogen (BUN), male and female rats were given a single dose of PBZ (125 mg/kg) and were sacrificed at different time intervals, from 0 to 48 h. Gross and microscopic examination of the kidneys and gastrointestinal tract showed more pronounced renal and gastrointestinal lesions in surviving female than in male rats at the same doses. In PBZ treated male rats, BUN did not differ from control rats 48 h after PBZ administration. In female rats, BUN increased from 18 to 96 mg/100 ml 48 h after PBZ administration. After 7 days of PBZ treatment there was a greater increase of protein excretion in female than in male rats, but there were almost no sex differences in glucose excretion. Twelve hours after PBZ administration, renal PAH accumulation and gluconeogenesis were not different from controls in male rats but decreased in a dose-dependent fashion in females. A significant depletion of GSH and a significant increase in MDA content in liver and renal cortex occurred in female but not in male rats. In conclusion, the PBZ treatment was associated with nephrotoxic and gastrointestinal effects which could be detected earlier and were greater in female than in male rats. PMID- 2922768 TI - Toxicity studies with quinine hydrochloride. AB - Three-month studies in the rat, a rat embryo-toxicity study and a specific study to investigate ototoxicity were carried out with quinine hydrochloride. The results of these studies suggest an acceptable daily intake of 40 mg quinine hydrochloride for an adult. There were no indications of teratogenic effects and no indications of interference with auditory function in rats receiving up to 200 mg/kg. PMID- 2922769 TI - Site and pathogenesis of infarcts associated with carotid endarterectomy. AB - We analyzed perioperative strokes in 658 carotid endarterectomies with the purpose of explaining the pathogenesis from the morphologic aspect of the infarct on cerebral computed tomograms. All endarterectomies were performed with continuous electroencephalographic monitoring. Of the 42 ischemic strokes (6.4% of all endarterectomies), 34 could be studied. Seven infarcts were hemodynamically induced (five watershed infarcts, two patients with bilateral ischemia); all seven occurred during surgery. Twenty-three of the remaining 27 infarcts were within the territory of the middle cerebral artery (20) or anterior cerebral artery (three) and were probably of thromboembolic origin; 13 of these 23 occurred during surgery (57%). If intraoperative stroke was heralded by permanent electroencephalographic changes, these were not related to the moment of cross-clamping. In four patients the computed tomogram was normal. We believe these facts favor the hypothesis that thromboembolism is the most important factor in the pathogenesis of perioperative stroke associated with carotid endarterectomy under conditions of optimal cerebral monitoring. PMID- 2922770 TI - Prospective analysis of carotid endarterectomy and silent cerebral infarction in 97 patients. AB - To determine the incidence of perioperative silent cerebral infarction, 97 patients who underwent carotid endarterectomy were prospectively studied with preoperative and postoperative computed tomograms. Thirty-one of 96 patients (32%) had findings of cerebral infarction on preoperative computed tomograms. Silent cerebral infarction was found preoperatively in 17 patients (18%) (lacunar infarction in 10, cortical infarction in five, both cortical and lacunar infarctions in one, and cerebellar infarction in one). Transient ischemic attacks occurred in 10 of the 17 patients with silent cerebral infarction; however, symptoms were appropriate to the site in only five of these 10 patients. Fourteen of the 17 patients with silent cerebral infarction had a hemodynamically significant carotid stenosis, and seven patients had an ulcerated plaque on preoperative angiogram. The incidence of these lesions was similar to that found in the group of 66 patients without cerebral infarction. Endarterectomy specimens revealed a higher but not significantly different incidence of ulcerated plaque in the silent cerebral infarction group. There were no perioperative deaths. Following surgery, one patient (1%) with a preoperative silent cerebral infarction suffered a transient ischemic attack, and two patients (2%) with normal preoperative computed tomograms developed permanent neurologic deficits with new cortical infarctions on postoperative computed tomograms. No new silent cerebral infarctions were found on postoperative computed tomograms in any of the 97 patients. Our data suggest that silent cerebral infarction is a common preoperative finding with an as-yet unclear etiology and that carotid endarterectomy does not appear to be a cause. PMID- 2922771 TI - Incidence of transient ischemic attacks in Oxfordshire, England. AB - The Oxfordshire Community Stroke Project is a prospective register of all new cases of stroke and transient ischemic attack (TIA) in a population of 105,000 residents of Oxfordshire, England. Between November 1, 1981, and October 31, 1986, 184 patients presented for the first time to a general practitioner or hospital with a TIA. The crude annual incidence rate was 0.35/1000, 0.42/1000 standardized to the 1981 population of England and Wales. We estimate that each year approximately 21,000 patients in England and Wales (about half of whom are greater than 70 years old) consult a doctor for the first time with a TIA. Approximately 80% of our 184 patients had TIAs in the carotid distribution; the remainder had TIAs in the vertebrobasilar distribution or TIAs of uncertain vascular distribution. The incidence of TIA increased sharply with increasing age, and the overall incidence in men was very similar to that in women (incidence ratio 1.3). However, in middle age, men were much more likely to suffer a TIA than women (odds ratio 2.6), which probably explains the marked male predominance in most hospital-based studies and treatment trials in which the elderly, and thus women, are underrepresented. This has important implications for the design and interpretation of clinical trials of treatment for TIAs. PMID- 2922773 TI - Changes in survival following stroke in five North Carolina counties observed during two different periods. AB - We evaluated survival following stroke for patients from a five-county area of rural North Carolina enrolled in either of two community hospital-based stroke survey programs. In this area, the first program enrolled 843 stroke patients between 1970 and 1973 and the second program enrolled 786 stroke patients between 1979 and 1980. One-year survival increased from 49% in the first program to 62% in the second for all stroke patients, from 54% to 68% for patients with cerebral infarction, and from 18% to 55% for patients with cerebral hemorrhage. While other reports have attributed declining stroke mortality to a decline in the incidence of stroke, our study suggests that increased survival after stroke may account for a large portion of the decrease in stroke mortality. PMID- 2922772 TI - Differences in mortality and cardiovascular morbidity during a 3-year follow-up of transient ischemic attacks and minor strokes. AB - We prospectively followed 78 patients with transient ischemic attacks (TIAs) from the carotid artery territory and 45 patients with minor ischemic strokes for 3 years. The mean +/- SD age of the patients in the TIA group was 66.9 +/- 7.9 years compared with 68.8 +/- 6.7 in the minor stroke group. Mortality among the TIA patients was significantly higher than that among minor stroke patients (18 of 78 compared with two of 45, p less than 0.01); mortality in the minor stroke group was not higher than that in the background population, whereas mortality in the TIA group was almost twice as high. The most common cause of death in the TIA group was myocardial infarction, and morbidity due to myocardial infarction and new TIA was higher in the TIA group than in the minor stroke group (35 events compared with seven), whereas no difference was found regarding stroke (five strokes compared with eight). Preexisting vascular disease implied an increased risk of mortality and morbidity in the TIA group. We conclude that carotid territory TIA indicates a worse prognosis than minor stroke as mortality is higher in TIA patients at the same preexisting vascular disease prevalence and stroke frequency. PMID- 2922774 TI - Destinations of stroke patients discharged from the Montreal area acute-care hospitals. AB - The destinations of stroke patients after discharge from acute-care hospitals were studied to ascertain the current use of health care resources. The 1984-1985 acute-care hospital discharge listings for the province of Quebec were consulted to identify 3,045 adults of the Montreal area who were discharged, deceased or alive, with a primary or secondary diagnosis of stroke. The relation between the length of stay (i.e., the time to death or discharge to long-term care, rehabilitation, or home) and the explanatory variables (age, sex, neighborhood socioeconomic status, type of stroke, and university affiliation of the discharging hospital) was assessed using Cox's proportional hazards models. Older patients and those with hemorrhagic strokes had the highest risk of death. However, patients with hemorrhagic strokes were more likely to survive if admitted to a university teaching hospital. Older patients, those with nonhemorrhagic strokes, and those admitted to university teaching hospitals were more likely to be discharged to long-term care. A greater proportion of patients discharged to rehabilitation centers were young, lived in a high-socioeconomic status neighborhood, and had suffered a nonhemorrhagic stroke. Patients had a significantly higher probability of going home if they were young, had had a nonhemorrhagic stroke, had been admitted to a university teaching hospital, or were male. PMID- 2922775 TI - Streptokinase treatment versus calcium overload blockade in experimental thromboembolic stroke. AB - Thromboembolic brain ischemia was produced in dogs using an autologous blood clot model. The effect of postembolic treatment with flunarizine and streptokinase on hemispheric cerebral metabolic rate for oxygen (CMRO2), oxygen extraction ratio (OER), and cerebral blood flow (CBF) was studied by positron emission tomography (oxygen-15 technique) 24 hours after the insult. We studied five groups of experimental dogs and compared them with a control group of nonembolized dogs. Group I received no treatment, Group II was treated locally with 500,000 IU streptokinase starting 30 minutes after the insult, Group III received streptokinase locally 30 minutes after the insult and 0.1 mg/kg i.v. flunarizine immediately after the insult and 2 hours later, Group IV received flunarizine as Group III, and Group V was orally pretreated with 0.5 mg/kg/day flunarizine during 2 weeks preceding embolization. Compared with the contralateral hemisphere, in the embolized hemisphere a significant reduction of CMRO2 (-25% to -40%) and CBF in normocapnia (-35%) and hypercapnia (-50%) was observed in Groups I, II, and V. In Groups III and IV, CMRO2, OER, and CBF of the embolized hemisphere were within the normal range during normocapnia and hypercapnia; the extent of the ischemic lesions was markedly less than in the other groups of experimental dogs. We conclude that flunarizine treatment after experimental thromboembolic stroke had a favorable influence on brain tissue. Chronic preventive flunarizine treatment failed to have a beneficial effect. PMID- 2922776 TI - Spinal cord blood flow and systemic blood pressure after experimental spinal cord injury in rats. AB - We looked at the relation between systemic arterial blood pressure and recovery from spinal cord injury by inducing both hypertension and hypotension in 25 rats randomly allocated to five equal groups. The rats received no injury, a mild (2.3 g), or a severe (53.0-g) spinal cord injury lasting 1 minute. We used the hydrogen clearance technique to measure spinal cord blood flow at the injury site (T1) and at an adjacent site (C6). Mean systemic arterial blood pressure was either increased with adrenaline or decreased by phlebotomy in 20-mm-Hg intervals except for the severe-injury group, in which the posttraumatic pressure could only be increased with adrenaline. Spinal cord blood flow remained constant in the no-injury group between 81 and 180 mm Hg. After a mild injury, induced moderate hypertension (121-140 mm Hg) improved spinal cord blood flow significantly, whereas hypotension decreased it in a linear fashion. Severe injury caused a marked decrease in spinal cord blood flow and mean systemic arterial blood pressure. Even extreme hypertension (161-180 mm Hg) induced by adrenaline did not significantly increase spinal cord blood flow at T1 but caused hyperemia at C6 due to loss of autoregulation. In conclusion, normotension should be attempted, irrespective of the severity of spinal cord injury. Induced hypertension after severe spinal cord injury was not beneficial in improving spinal cord blood flow at the injury site while potentially increasing hemorrhage and edema. PMID- 2922777 TI - Tolerance of the cerebral venous system to retrograde perfusion pressure in focal cerebral ischemia in rats. AB - Using quantitative double-tracer autoradiography, we examined the tolerance of the rat cerebral venous system in focal cerebral ischemia to retrograde perfusion pressure into the inferior cerebral vein. At perfusion pressures of less than 150 mm Hg, there was no significant change in local cerebral blood flow (LCBF) and blood-brain barrier (BBB) permeability. At pressures of greater than 170 mm Hg, significant changes occurred in BBB permeability in the superficial cortical layers and there was a mild reduction of LCBF. In the group of rats subjected to 200 mm Hg perfusion pressure, the change in BBB permeability extended to the entire cortical zone and significant reduction of LCBF occurred. Our results indicate for the first time that during conditions of focal cerebral ischemia, the rat cerebral venous system can tolerate up to 150 mm Hg of retrograde perfusion pressure into the cerebral venous system without any change in BBB permeability or in LCBF. However, progressive change in BBB permeability and reduction in LCBF occur once the perfusion pressure exceeds 170 mm Hg. This finding may permit more efficient delivery of cytoprotective agents into ischemic tissue. PMID- 2922778 TI - Pathogenesis of transient ischemic attacks and stroke in baboons. AB - We describe a series of experiments in which a subhuman primate model was used to create temporary and permanent cerebral ischemia by three separate mechanisms. In the first group of five baboons, a hemodynamic model was produced by creating unilateral and bilateral carotid stenotic lesions of varying degrees with and without associated reduction in systemic perfusion pressure. Only global ischemic changes and no focal changes resulted. In the second group of three baboons, a macroembolic model was produced by introducing solid particulate material into the extracranial circulation. No reversible contralateral focal neurologic changes resulted. In the third group of 11 baboons, cerebral ischemia was produced by introducing agents known to cause platelet aggregation (arachidonic acid, adenosine diphosphate, and collagen) into the extracranial arterial circulation. Arachidonic acid caused seizures, adenosine diphosphate caused severe postural hypotension, and only collagen fibrils produced a picture resembling a transient ischemic attack. We propose a theory that intravascular activation of the prostaglandin cascade by chemical initiation may result in the pathophysiologic changes of transient cerebral ischemia. PMID- 2922779 TI - Influence of granulocytopenia on canine cerebral ischemia induced by air embolism. AB - We subjected nine dogs with severe granulocytopenia 4 days after the administration of mechlorethamine to 1 hour of cerebral ischemia induced by the controlled, incremental injection of air into the internal carotid artery. Cortical somatosensory evoked responses and cerebral blood flow determined by [14C]iodoantipyrine autoradiography were compared with those of six control dogs that had received mechlorethamine 1 day previously and were not yet granulocytopenic. Eleven additional control dogs received no mechlorethamine but had identical ischemic insults and were followed for 4 hours after ischemia. Both control groups had identical evoked response outcomes after 1 hour of recovery from ischemia. Granulocytopenic dogs had improved evoked response recoveries compared with either control group after 1 hour of recovery. No areas of very low blood flow were observed 1 hour after ischemia in the granulocytopenic dogs, but three of five dogs in the control group receiving mechlorethamine had such areas. PMID- 2922780 TI - Sarcoidosis presenting with stroke. AB - A 25-year-old black man with sarcoidosis presented with transient ischemic attacks followed by sudden, persistent right hemiparesis. He gave a history of recent, recurrent lower motor neuron facial palsy. Computed tomography demonstrated an infarct in the left internal capsule. Chest x-ray film showed bilateral hilar and mediastinal lymphadenopathy and multiple opacities in the lung fields. Serum angiotensin converting enzyme concentration was raised, and a Kveim test was positive for sarcoidosis. Despite clear pathologic reports of cerebral vasculitis in neurosarcoidosis, the occurrence of stroke is extremely rare. PMID- 2922781 TI - Pure sensory stroke due to a pontine lacune. AB - A 53-year-old hypertensive man presented with the sudden onset of an isolated lemniscal sensory syndrome of the entire left side of his body. Magnetic resonance images showed a small lacune in the right paramedian pons corresponding to the location of the medial lemniscus. PMID- 2922782 TI - Occipital infarction with hemianopsia from carotid occlusive disease. AB - Extracranial internal carotid artery occlusive disease usually produces stroke in the middle cerebral artery territory or the border zone between the middle and anterior cerebral arteries. It is unusual for occipital infarction in the posterior cerebral artery territory to be caused by internal carotid artery disease despite the fact that the posterior cerebral artery may arise directly from the internal carotid artery as an anatomic variation. We describe a patient with a fetal posterior cerebral artery originating from the internal carotid artery, and the initial manifestation of his extracranial internal carotid artery occlusive disease was hemianopsia from occipital infarction. PMID- 2922783 TI - Blunt traumatic carotid dissection with delayed symptoms. AB - We describe five patients with blunt traumatic carotid dissection with delayed clinical presentation that varied from 2 weeks to 6 months. Four patients had severe head injury, and one patient had direct blunt trauma to the neck. Cerebrovascular symptoms developed in four patients. The fifth patient suffered loss of vision as a result of a concurrent giant intracranial dissecting aneurysm. Arteriography demonstrated a "string sign" in two cases and a cervical carotid aneurysm in three; two of the latter also had siphon occlusion, and one of these had a superimposed supraclinoid dissecting aneurysm. One patient was treated by thromboendarterectomy, one by aneurysmorraphy, another by carotid ligation, and the other two patients were treated medically. Mechanisms of injury, forensic problems, and therapeutic options are discussed. PMID- 2922784 TI - Trauma: a personal perspective. AB - 1. Empathic caring is essential to deliver high-quality nursing care. 2. As nurses, we need to understand what patients are feeling to help decrease their emotional trauma. 3. Many OR patients do not have the luxury of good support systems, familiarity with caregivers and environment, and a medical knowledge base to enhance understanding. PMID- 2922785 TI - OR experiences are for student nurses. AB - 1. The media, lack of appropriate socializing comments regarding clinical nursing specialties and unavailable rotations may contribute to a student nurse's negative conception of RNs who work in the OR care environment. 2. Developing a project of this kind has informal and formal parameters. Informal parameters are based on becoming familiar with OR constructs; formal parameters are established by reviewing the mission statement and philosophy of both the nursing education program and that of the health-care institution. 3. Nonprivate, non-parochial, university-affiliated agencies welcome student learning experiences and have the time, place and people resources to support them. However, private, for-profit or free-standing health-care agencies may require contracts as documentation of the goals and motivations for the activities. PMID- 2922786 TI - A training system for first and solo assistants in microsurgery. AB - 1. A system to train nurses to be first and solo assistants of microsurgery has been practiced in our hospital for the past 13 years. 2. Under our unique weekly rotation system, nurses are educated to be all-around nurses. Microsurgical assistance is only one of approximately eight sections of the rotation. 3. Under this system, nurses can become extremely efficient solo assistants after 3 years. PMID- 2922787 TI - Teddy bear clinic. AB - 1. The Shriners Institute in Boston developed a day to educate children about hospitals and the OR environment. 2. OR nurses have instituted extensive procedures and policies to allow potential patients the information they need to know their rights. 3. The most important instruction was for the children to ask those questions that they thought their teddy bears might ask. PMID- 2922788 TI - Posttransfusion survival of red cells frozen for 8 weeks after 42-day liquid storage in AS-3. AB - Current standards recommend that red cells (RBCs) should be frozen within 6 days of donation. There are situations, however, in which it is desirable to freeze RBCs that are older than 6 days, such as for the salvage of rare or autologous units. To determine the therapeutic efficacy of RBCs frozen after prolonged liquid storage, standard units were drawn from nine normal donors and stored at 4 degrees C for 42 days in a nutrient-additive solution, AS-3. 51CrRBC survival assays were performed (24-hour survival: 78.2 +/- 12.4%; n = 8) and the units were frozen at -80 degrees C in glycerol for 8 weeks. After deglycerolization, the mean RBC recovery was 81.0 +/- 4.1 percent and the mean 24-hour 51Cr survival was 78.0 +/- 9.1 percent. The index of therapeutic effectiveness (ITE) was determined by multiplying the postdeglycerolization 24-hour 51Cr survival by the mean RBC recovery (63.3 +/- 9.2). ITE values greater than 60 percent (75% 51Cr survival x 80% RBC recovery) were considered acceptable. Mean adenosine triphosphate levels declined from an initial 3.81 +/- 0.56 micromol per g of hemoglobin to 2.33 +/- 0.55 micromol per g after frozen storage. These findings show that an acceptable percentage of RBCs survives frozen storage after maximum liquid storage (mean ITE greater than 60%). If necessary, RBCs stored in AS-3 can be frozen at any time before 42 days. PMID- 2922789 TI - Polyethylene glycol improves the indirect antiglobulin test. AB - PEG3350, a linear polymer of ethylene glycol, was evaluated as a potentiator of the indirect antiglobulin test (IAGT). The polymer enhances the avidity and affinity of clinically significant red cell alloantibodies than those obtained with bovine serum albumin (BSA). The sensitivity and specificity of the PEG mediated reactions were superior to those obtained with BSA. Subpopulations of red cells, such as those encountered with fetomaternal hemorrhages, were detected at lower concentrations with PEG than with BSA using the microscopic Du test. The superiority of the PEG reaction, its simplicity, and the reagent's relatively low cost make substitution of the polymer for BSA in the IAGT an attractive option. PMID- 2922790 TI - Extended survival of neocytes produced by a new system. AB - Red cells (RBCs) prepared by a new system using centrifugation to produce neocyte enrichment were studied in two laboratories. The system used a blood bag with a geometric configuration such that younger, less dense cells could be separated from older, denser cells. Phthalate ester density gradient curves determined that neocyte enrichment was 81.3 percent in one laboratory and 82 percent in the other. RBC viability was studied by 51Cr autologous transfusion in normal volunteer donors. A randomized, paired design was used in which each donor was transfused once each with neocytes and with RBCs of all ages. The mean control half-life was 34.8 +/- 5.4 days in one laboratory and 34.0 +/- 3.6 days in the other. The mean half-life of the neocyte-enriched RBCs was 45.2 +/- 8.2 days in one laboratory and 45.1 +/- 4.4 days in the other. This represented a more than 30 percent increase in half-life for the neocyte-enriched RBCs, a significant difference. This new system, a two-bag set that costs +15, allows the simple, efficient separation of neocyte-enriched RBCs that would have a longer half-life and could reduce the transfusion requirement in patients receiving chronic transfusion therapy. PMID- 2922791 TI - The effect of additives on red cell 2,3 diphosphoglycerate levels in CPDA preservatives. AB - Forty-two chemical substances, chosen because they might influence red cell metabolism, were screened for effect on red cell adenosine triphosphate and 2,3 diphosphoglycerate (2,3 DPG) levels during storage in CPD or CPDA-1 at 4 degrees C. Of these substances, six appeared on initial screening to increase 2,3 DPG levels during storage; on repeated examination, four compounds, i.e., oxalate, glyoxalate, ethyl oxaloacetate, and L-phenylalanyl-L-alanine, consistently increased 2,3 DPG levels during storage. It was shown that glyoxalate was converted rapidly to oxalate in blood, presumably through the lactate dehydrogenase reaction. Ethyl oxaloacetate is known to hydrolyze, giving rise to oxalate. Thus, the effect of both glyoxalate and ethyl oxaloacetate can be explained by the formation of oxalate, a compound already known to increase 2,3 DPG levels. The effect of L-phenylalanyl-L-alanine remains to be explained, but it may be hydrolyzed to L-alanine and L-phenylalanine, both of which are thought to have the capacity to increase red cell 2,3 DPG levels by inhibiting pyruvate kinase activity. PMID- 2922792 TI - Blood group phenotypes in Taiwan. AB - This report describes a study of 31 red cell antigens in 13 blood group systems tested over a period of 3 years in the Chinese population of Taiwan. The study provides evidence that major differences exist between Taiwanese and whites or blacks in five blood group systems: Rh, MNSs, Duffy, P, and Xg. PMID- 2922793 TI - Absence of HIV-1 infection in antibody-negative sexual partners of HIV-1 infected hemophiliacs. AB - In order to confirm the presence and determine the frequency of human immunodeficiency virus, type 1 (HIV-1) infection prior to antibody production, 23 healthy women with histories of repeated unprotected sexual exposure to HIV-1 infected hemophiliacs were tested for evidence of HIV-1 infection. Female subjects were tested for HIV-1 antibody (enzyme immunoassay [EIA] and Western blot), HIV-1 serum antigen, HIV-1 DNA gag sequences by the polymerase chain reaction, and HIV-1 virus isolation from peripheral mononuclear cells. Twenty-two of 23 (96%) women were negative by all HIV-1 assays. One woman was positive by all the HIV-1 assays including an EIA screening test for HIV-1 antibody. These preliminary results suggest that the frequency of HIV-1 infection in antibody negative sexual partners of HIV-1 infected individuals is probably very low. PMID- 2922794 TI - A prospective study evaluating the lowering of hemoglobin standards for blood donors. AB - Strict regulations exist for the selection of blood donors. These include minimum hemoglobin (Hb) standards of 13.5 and 12.5 g/dL for males and females respectively. In Canada 2% of all blood donors, or approximately 25,000 individuals annually attempt to make a blood donation but are deferred because their Hb level does not meet these minimum accepted standards. In a previous study we provided a biostatistical approach to ascertain objectively the optimal minimum Hb standards for blood donors to best discriminate between iron deficient and non iron deficient individuals. The derived values were lower than the existing minimum Hb standards and because of concern that blood donors accepted using these lower Hb standards might have asymptomatic disease, the proposed new levels were not adopted. This present prospective study was undertaken to assess the impact on the blood donors of the new Hb standards. Over 26 months we evaluated 1,558 donors (695 males and 863 females). On entry into the study they were screened for a variety of medical conditions which could result in asymptomatic anemia and 6 months later they answered a health questionnaire. Blood donors were entered into 1 of 3 groups. Group I were donors accepted by the existing criteria. Group II were donors who did not meet the existing Hb criteria but satisfied the newly derived standards. Group III were donors deferred even by the new Hb standards.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2922795 TI - The blood supply--safer than it has ever been. PMID- 2922796 TI - A citrate-dependent red cell antibody reactive only in bromelin. PMID- 2922797 TI - Limitations of paternity testing calculations revisited. PMID- 2922798 TI - Experimental validation of paternity probability. PMID- 2922799 TI - Microencapsulated parathyroid cells as a bioartificial parathyroid. In vivo studies. AB - Parathyroid cells were isolated from healthy rats, encapsulated in alginate polylysine membranes, and injected intraperitoneally into rats on which total parathyroidectomies had been performed. Three days posttransplant, serum calcium and PTH-M concentrations had increased to near-normal levels in the recipient animals. Similar results were observed in a separate group of parathyroidectomized rats 3 days after free parathyroid cells were implanted, but within 4 weeks serum calcium and PTH-M concentrations had decreased almost to pretransplant levels in these rats. In the rats with encapsulated cell transplants, by contrast, serum calcium and PTH-M levels were significantly higher, even after 8 weeks. No therapeutic effects were observed in rats injected with empty capsules or in the control group, which received no capsules or cells. These results indicate that transplants of microencapsulated parathyroid cells can temporarily reverse aparathyroidism in rats without the use of immunosuppressive drugs, and that further studies are warranted to investigate possible future clinical applications of this treatment. PMID- 2922801 TI - Graft-versus-host resistance induced by tolerant cell populations. Evidence against clonal deletion as a mechanism of transplantation tolerance. AB - Characterization of the effect of immunization of F1 hybrid hosts with low doses of parental cells has shown that the F1 hybrid response to the receptor for the unshared MHC antigen on the immunizing cell induces specific resistance to a GVH challenge from cells of the same parental strain. We have shown that cells from parental rats tolerant to the unshared MHC antigens are capable of inducing GVH resistance in F1 hybrids. Unlike cells from normal parental rats that induce GVH resistance only when given in low immunizing doses of 10(6) cells, 10(6)-10(8) cells from tolerant donors effectively immunize F1 hybrids. This effect does not appear to be the result of passive transfer of suppressor cells from the tolerant donor. An alternative explanation is that tolerant populations contain cells that express the receptor for the tolerated alloantigen. The finding that normal parental populations that have been deleted of receptor-bearing cells by passage through semiallogeneic intermediate hosts do not induce GVH resistance, whereas tolerant cell populations do, confirms that clonal deletion does not adequately account for the functional characteristics of the tolerant cells. Attempts to delete putative receptor-bearing cells from the tolerant population however produced equivocal results. PMID- 2922800 TI - Hepatic tolerance to hypotension as assessed by the changes in arterial ketone body ratio in the state of brain death. AB - Hepatic tolerance to hypotension was assessed by changes in arterial ketone body ratio (KBR) and hepatic energy charge levels in experimental brain death induced by epidural ballooning in dogs, and compared with the hemorrhagic shock model. Systolic arterial blood pressure was significantly decreased from 182 mmHg to 67 mmHg after completion of brain death (P less than 0.01), but KBR was maintained at near the control value of 1.098 +/- 0.051 in spite of marked hypotension. Hepatic energy charge was 0.846 +/- 0.016 and remained at normal level. No significant changes were observed in lactate level, total bilirubin, SGPT, and LDH. SGOT was slightly elevated but was still within normal limits (P less than 0.05). Light microscopic examination revealed no apparent ischemic change in the centrilobular region under hematoxylin and eosin staining. By contrast, KBR decreased from 0.975 +/- 0.054 to 0.273 +/- 0.060 following hypotension in the Wiggers' shock model (P less than 0.01). Lactate levels were gradually elevated significantly (P less than 0.05), but no significant increases were observed in total bilirubin, SGOT, SGPT, and LDH. It is suggested that the hepatic energy status is well maintained in the state of brain death, in which state the liver has high tolerance to marked hypotension until shortly before stoppage of the heart. PMID- 2922802 TI - The effect of cyclosporine on macrophage oxidative burst potential during graft versus-host reactions in mice. AB - The development of graft-versus-host reactions in mice was characterized by an increase in activated macrophage populations in the peritoneum and spleen of the animals. In the present study we tested the effect of the immunosuppressive agent CsA on the appearance and activity of such macrophages. Parental spleen lymphocytes were injected intraperitoneally into F1 hybrids (BALB/c x C57Bl/6), and 13 days following injection we monitored the number of peritoneal exudate cells (PEC), spleen enlargement, and the oxidative burst (OB) of adherent peritoneal macrophages (APM). Macrophage OB was assessed by measuring O2- and H2O2 production, following stimulation with 12-O-tetradecanoyl-phorbol-13-acetate (TPA). In GVHR mice a 72% increase in their spleen to body weight ratio was observed, whereas in CsA-treated GVHR mice only a 32% increase was evident. Assessment of the effect of CsA on the number and function of peritoneal cells revealed that CsA caused a 73% reduction in the number of infiltrating PEC in GVHR mice. Furthermore, measurements of H2O2 and O2- production by APM revealed that the overall OB capacity of APM from CsA-treated mice was significantly reduced compared to APM from nontreated GVHR mice. CsA had no effect on the number and OB activity of paraffin oil elicited or resident PEC. These results indicate that CsA may prevent recall and activation of macrophages via its effect on T cell lymphokine release and thus may lessen the contribution of macrophage derived toxic reagents to the damage inflicted by GVHR. PMID- 2922803 TI - Correlation between two radioimmunoassay methods for cyclosporine determination. PMID- 2922804 TI - Transient cortical blindness and occipital seizures with cyclosporine toxicity. PMID- 2922805 TI - New brooms. PMID- 2922806 TI - Stroke in a subsaharan Nigerian hospital--a retrospective study. AB - The case records of 53 consecutive Nigerian inpatients with stroke in the University of Maiduguri Teaching Hospital, Maiduguri were retrospectively reviewed. The mean age at presentation was 55 years and the male to female ratio was 2.5:1. The mean duration of symptoms before presentation was 11.1 weeks and the average duration of stay in hospital was 3 weeks. Thirty-three (63%) of the lesions were infarctive and 19 (37%) were haemorrhagic. Only 3 (6%) patients gave a history of prior transient ischaemic attacks (TIAs). Forty-two (79%) patients were hypertensive at presentation out of which 27 (64%) had the hypertension diagnosed for the first time. Four (8%) patients were non-insulin dependent diabetics. There were 11 hospital deaths (21%). Thus hypertension, more than half undiagnosed at admission, was the most common risk factor for stroke in the hospital population studied. PMID- 2922808 TI - Bangladesh National Drug Policy: an assessment. PMID- 2922807 TI - Infectious diseases in a Nicaraguan refugee camp in Costa Rica. AB - Some Nicaraguans living in Costa Rica are in refugee camps. The types and rates of infectious diseases in the Pueblo Nuevo refugee camp were measured by examining medical records for 1985 and performing stool and blood testing. The incidence of infections was 320 episodes per 1000 persons per year. Respiratory infections represented 63% of all illnesses and pulmonary tuberculosis was high. Malaria was not found in blood samples and no childhood illnesses preventable by immunizations were recorded in the records. Intestinal parasites were found in 56% of the persons examined, considerably higher than the 15% prevalence noted in surveys of Costa Rica as a whole. Trichuris trichiura was found in 40% of the positive stool samples. The deficient hygienic conditions and overcrowding in the camp are responsible for the high rates of infections and the continued presence of infections many of which probably were acquired in Nicaragua. Improvement of hygienic conditions can be accomplished by involving the refugees in education, cleaning and identifying problem areas. Adequate sanitation and improved water supply, and reducing overcrowding are also recommended. PMID- 2922809 TI - Knee surgery and the Indian knee. The importance of the preservation of flexion. AB - The pattern of knee pathology seen in an Indian mission hospital following the introduction of knee clinics is described. This paper reports the results of the first 200 consecutive patients seen at these clinics, relating the findings to anticipated treatments. The occurrence of degenerative disease was high. The importance of knee flexion, in order to be able to squat, is highlighted. The necessity to adopt this position materially alters the types of treatment that can be offered to this group of people. It is concluded that treatments common to the West are not always suitable for patients in the Third World. PMID- 2922811 TI - Temporary colostomy as a permanent treatment for sigmoid volvulus: a simple and safe one-stage procedure. PMID- 2922810 TI - Experience with 103 cases of intestinal gangrene in Ile-Ife, Nigeria. AB - One hundred and three patients with intestinal gangrene were managed in Ile-Ife, Nigeria over a 10-year period. The overall mortality in the series was 25.2%. Strangulated hernias were responsible for 65 cases (63%), intussusception 20.4%, adhesions 11.7% and volvulus 2.9%. Avoidable deaths resulted from anastomotic breakdown and inadequate preoperative fluid therapy. Primary intestinal resection and end-to-end anastomosis of large bowel involved in gangrene gave very good results. It was found to be quite safe and economical, and avoided the inconveniences and complications of a colostomy. PMID- 2922812 TI - Monitoring polio trends from physiotherapy records. Independent sentinel surveillance in Pakistan. PMID- 2922813 TI - Pulmonary tuberculosis complicated by bronchopleural fistula. PMID- 2922814 TI - Oesophageal cancer in Sudan. PMID- 2922815 TI - Ocular trauma. AB - Well over half a million people in the world are blind as a result of eye injuries. It is not known how much of the final visual damage is the result of delayed or inappropriate management at the primary care level. However, it is certain that the outcome of ocular trauma by prompt action that will prevent serious loss of sight. He or she requires neither specialist knowledge, nor expensive instruments, but only the common sense application of a few basic clinical skills. PMID- 2922817 TI - Paediatric resuscitation: appropriate equipment. PMID- 2922816 TI - Treating childhood respiratory illness in developing countries: mist therapy without electricity. AB - We have developed an effective and well-accepted method of providing mist for children with acute respiratory distress. This method can be especially useful in areas of the world where resources are limited. PMID- 2922818 TI - Cranial surgery in a rural Kenyan hospital. PMID- 2922819 TI - Primary health care with limited resources. PMID- 2922821 TI - Successful abdominal pregnancy. PMID- 2922820 TI - Response to drug treatment in children with chronic anaemia. PMID- 2922822 TI - Ketamine drip anaesthesia for Caesarean section. PMID- 2922823 TI - Non-traumatic coma in Zambia. AB - A series of 170 patients with non-traumatic coma seen over a 16-month period is reported. The Glasgow coma scale significantly correlated with outcome (P less than 0.001). The diagnosis was also important in determining outcome. Hospital mortality was lowest in patients with cerebral malaria (22.7%), eclamptic coma (36.4%), and organophosphorous poisoning (30.4%). A diagnostic approach to non traumatic coma is outlined and the management of the different causes is discussed. Most hospitals in tropical Africa should be able to diagnose up to 90% of cases with non-traumatic coma and simple therapy is likely to be effective in the majority of cases. PMID- 2922824 TI - [MRI--where do we stand]. PMID- 2922825 TI - [The effect of anabolic androgenic steroids on muscle strength, body weight and lean body mass in body-building men]. AB - A review of the effects of anabolic-androgenic steroids (AAS) on muscle strength, body weight and lean body mass in body-building men is presented. In about half of the placebo-controlled studies, a significant effect on the above mentioned response variables is found. In all cases where an effect was achieved, the drug used was methandrostenolone or stanozolol. Whether this is connected with a special quality of these AAS or whether the negative results achieved with the other AAS are caused by type 2 error is not yet known. The use of AAS as ergogenic drugs must be deprecated because of their marginal effects, the risks of side effects and the unsporting, unethical aspects. PMID- 2922827 TI - [Drug addiction and HIV infection]. AB - HIV infection has spread rapidly among intravenous drug addicts. In Denmark, the infection is limited to Copenhagen where the prevalence is 10-25%. Improved supervision of this partial epidemic is essential. The measures instituted to limit spread of infection are still inadequate. PMID- 2922826 TI - [HIV infection among homosexual and bisexual men in Denmark. Occurrence and transmission]. AB - In Denmark, AIDS has primarily affected men with homosexual behavior. In order to follow the occurrence and development in this group, the sero-epidemiological investigations which focus on the underlying HIV epidemic are reviewed. HIV was introduced in Denmark towards the end of the nineteen-seventies and spread rapidly in the beginning of the nineteen-eighties among promiscuous homosexual men in Copenhagen to a level in which 1/4-1/3 were found to be infected in small selected materials. From the middle of the nineteen-eighties, decreasing tendencies were observed in the numbers of homosexual and bisexual men in whom antibodies to HIV were demonstrated for the first time. Epidemiological evidence suggests that the rate of spread of HIV among homosexual men slowed down in the second half of the nineteen-eighties. In 1985, it was estimated that at least 6,000 homosexual men were infected with HIV. No investigations justify new increased estimates of the numbers of HIV-infected homo- and bisexual men in Denmark. Epidemiological data demonstrate clearly that unprotected receptive anal coitus is the main route of infection for homosexually transmitted HIV. The risk of infection appears to be much lower for the active partner in anal coitus with an HIV-infected man. No epidemiological investigations have demonstrated oral sex as the route of infection for HIV among men although this does not exclude the possibility of HIV-infection in occasional cases of oral sex. PMID- 2922828 TI - [Massive feto-maternal hemorrhage. Diagnosis, quantitation, etiology and (para clinical findings)]. AB - Massive feto-maternal haemorrhage occurs with a frequency of approximately 1 out of 1,000 deliveries and involves a considerable risk for intrauterine/perinatal morbidity and mortality. Three cases of massive feto-maternal haemorrhage are described. Methods of diagnosis and quantitation are reviewed. The etiological conditions are briefly mentioned and clinical and paraclinical aspects in the fetus/infant and also the mother are reviewed. Investigation for feto-maternal haemorrhage should be undertaken in all cases of unexplained stillbirth and perinatal death and in all cases with hypovolaemic shock or non-haemolytic anaemia in neonates. In addition, investigation should be undertaken in selected cases with deterioration of fetal condition after eg trauma to the uterus, external version and amniocentesis, particularly in cases with massive vaginal haemorrhage and/or aspiration of haemorrhagic amniotic fluid. In these latter cases, it may also be of value to carry out Kleihauer's test on aspirate from the vagina and/or amniotic fluid with the object of determining whether the haemorrhage is of fetal or maternal origin. PMID- 2922829 TI - [Self-reported pattern of illness and hospitalization during pregnancy. Results from a nation-wide questionnaire study]. AB - In a representative questionnaire investigation covering all of Denmark, 3,152 women provided information about their health during a recent pregnancy. Of these, 1,411 (45%) had been ill or had experienced severe complaints related to the pregnancy and 625 (20%) had been hospitalized during pregnancy. The average duration of hospitalization was two weeks with great variations in the various conditions. Women with multiple pregnancies were hospitalized for an average of six weeks. Increased incidence of hypertension and placental insufficiency were found among women over the age of 35 years whereas preeclampsia was most common among primigravidae. Women who had previously had a spontaneous abortion had an increased frequency of haemorrhage, threatened abortion and threatened premature delivery. Previous infertility was not associated with increased occurrence of complications of pregnancy-related morbidity were observed between women who had work outside the home and women who worked in their homes. Women with work outside the home who reported illness or severe pregnancy-related symptoms had an average period of sick-leave of six weeks for health reasons. The most prolonged periods of sick-leave were in cases of threatened abortion, threatened premature delivery and multiple pregnancies. The right to take leave with pay or maintenance allowance prior to the expected date of delivery is not utilized to any great extent more by women with illness during pregnancy. On the other hand, women with long educations utilized this right to a greater extent than unskilled women, who had, on the other hand increased leave on account of health reasons. PMID- 2922830 TI - [Is hepatitis B antigenemia a risk in adjuvant cytostatic treatment of breast cancer?]. AB - One-hundred and fifteen consecutive patients with breast cancer were examined for hepatitis B. All the patients received adjuvant chemotherapy. The median age was 46 years (range 26-54 years). None of the patients were found to be HBsAg positive. The prevalence of HbsAg was within the limits of 0-0.026 (95% confidence interval). Vaccination of patients receiving chemotherapy is not indicated. Furthermore, regular HBsAg screening among patients under 55 years cannot be recommended. PMID- 2922831 TI - [Bruising after venepuncture]. AB - A randomized cross-over investigation was carried out on 24 healthy volunteers to investigate the occurrence of bruising following compression on the extended or flexed elbow respectively, following venepuncture in the cubital fossa. Following 48 uncomplicated venepunctures (24 x 2) a total of 8 (17%) were found to have bruising, four of these after compression on the extended elbow and four after compression on the flexed elbow. It is concluded that there are no differences in the frequencies of bruising following closed venepuncture in the cubital fossa regardless of whether the subsequent compression is undertaken on the extended or flexed elbow. PMID- 2922832 TI - [The Angelchik prosthesis in the treatment of gastroesophageal reflux]. AB - Eighteen patients were treated for severe symptomatic gastroesophageal reflux with insertion of an Angelchik prosthesis. Three months after the operation all were free of symptoms. Postoperative 12-hour intra-esophageal pH monitoring showed significant reduction in acid reflux. Basal gastroesophageal sphincter pressure did not change significantly. After three years, one of the patients had symptomatic relapse. We conclude that the Angelchik prosthesis is effective in the treatment of symptomatic gastro-esophageal reflux, and that it is an alternative to conventional surgical procedures. PMID- 2922833 TI - [Electrocoagulation as radical treatment of anorectal cancer]. AB - During a 17 year period, 19 patients with ano-rectal cancers were treated radically by electrocoagulation. Ten patients (52%) were treated successfully with electrocoagulation as the only treatment. The method is recommended as an alternative to radical surgery in carefully selected patients. The patients should be followed up at regular intervals. No serious complications occurred. PMID- 2922834 TI - [Mesenteric cysts in Denmark in 1980-86]. AB - On the basis of a material of mesenteric cysts from a period of six years in all Denmark, the symptomatology, diagnosis and treatment of mesenteric cysts (MC) are described. These cysts are rare: approximately one par 130,000 somatic admissions. Mesenteric cysts may be encountered along the entire gastro intestinal canal from the duodenum to the rectum but are, however, most frequent in the mesentery of the small intestine. The symptoms were variable and depended upon the site, mobility, tension on the mesentery, the complications and, to a lesser extent, on the size. Ultrasonic scanning was the most important diagnostic aid. 5% of the cysts contained chyle and up to one third of these are stated to be malignant. Computed tomographic scanning is recommended preoperative as the density can reveal whether the content is chylous. Enucleation of mesenteric cysts would be attempted but, in cases of large cysts which prove difficult to resect, internal marsupialization may be employed. Material with low frequencies of recurrence and few complications have been presented employing this therapeutic method. PMID- 2922835 TI - [Hearing disorders--what do we know?]. AB - The object of this investigation is to describe persons with hearing defects knowledge about and the offers of help from the service for the deaf and, simultaneously, to describe the attitudes in the primary health sector to hearing problems and knowledge about the audiological possibilities in the hospital sector. One hundred and three consecutive persons referred to the service for the deaf for the first time (35 men and 68 women with an average of 74 years, range 15-94 years) were included in the investigation. The sex and age distributions were representative for the adult patient clientele in this department. On investigation in the department, the patients replied to a questionnaire which could reveal: the complaint which had led to referral to the department; how possible hearing problems had been discovered; why the patient sought help just now; how long the problem had been present; the treatment he/she expected to result from the investigation; whether the patient had previously discussed the hearing problem with the ENT specialist or his own general practitioner. 86% sought help in the department on account of hearing problems which had most frequently been noticed by the patient himself and his family. 55% had had the problem for one to five years and only 13% had had the problem for one year or less. 26% had experienced the hearing problem for more than five years. 59% expected relief of the problem in the form of a hearing aid, while 28% had no expectations about improvement or relief of their problem.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2922836 TI - [Endoscopic treatment of acute colonic pseudo-obstruction]. AB - Four patients admitted on account of various extracolonic conditions developed acute pseudo-obstruction of the colon during hospitalisation. All of these were successfully treated with colonoscopic decompression. The technique is described. PMID- 2922837 TI - [Perforation of the rectosigmoid colon following autoerotic manipulation]. AB - A case of perforation of the rectosigmoid colon following autoerotic transanal manipulation with a billiard cue is presented. The indications for operation and aids for removal of foreign bodies in the rectum are discussed. PMID- 2922838 TI - [Giant cell arteritis and gangrene of the tongue]. AB - A case of loss of the tongue on account of infarction in a patient with temporal arteritis is described. Causal factors including temporal arteritis are briefly discussed. PMID- 2922839 TI - [Giant diverticulum of the sigmoid colon]. AB - A case of a giant sigmoid diverticulum is presented with a review of clinical and radiological features and surgical treatment. The origin is discussed in relation to a peroperative observation of air-trapping. PMID- 2922840 TI - [A permanent pacemaker with variable frequency]. PMID- 2922841 TI - [Continuing studies on wake therapy of endogenous depression--physiological principles and realization]. PMID- 2922842 TI - [Postoperative urine retention]. PMID- 2922843 TI - [Nature and extension of drug information to general practitioners. A questionnaire study]. PMID- 2922844 TI - International Conference on Medicine and Law, Prague, August 1988. Education in ethics for the medical and legal profession as a mean of preventing the involvement of doctors and lawyers in torture and other inhumane procedures. PMID- 2922845 TI - [Notification of occupational diseases from general practice during the period 1978-1987]. PMID- 2922846 TI - [Terminal care, information and cooperation]. PMID- 2922847 TI - [Toxic effects of anesthetic waste gases]. PMID- 2922848 TI - [Deliberations on the future organization of diagnostic and treatment control of hyperlipidemia. Experiences from the county of Funen]. PMID- 2922849 TI - [Diagnosis of hyperlipidemia in patients admitted with acute myocardial infarction]. PMID- 2922850 TI - [Hyperlipidemia in patients under 60 years of age admitted for suspected myocardial infarction]. PMID- 2922851 TI - [Terminal care of cancer patients. 1. Frequency and clinical problems]. PMID- 2922852 TI - [Terminal care of cancer patients. 2. Communication and cooperation]. PMID- 2922853 TI - [Terminal care of cancer patients. 3. Problems and suggestions for improvement]. PMID- 2922854 TI - [Mortality rates in alcoholic and non-alcoholic liver cirrhosis in Denmark]. PMID- 2922855 TI - [Bilateral Freiberg's disease. Clinical and radiologic onset after age 44]. PMID- 2922856 TI - [Thyroid cancer in Denmark during the period 1943-85. Cancer statistics number 23]. PMID- 2922857 TI - [International Union against Tuberculosis and Lung Disease]. PMID- 2922858 TI - [Hypertension and anesthesia]. PMID- 2922859 TI - [Zopiclone (imovane)--a new sedative agent]. PMID- 2922860 TI - [The Radical Party wishes to change the function of school physicians]. PMID- 2922861 TI - [Health and disease]. PMID- 2922862 TI - [Ventricular pseudoaneurysm after acute myocardial infarction]. AB - Left ventricular aneurysm is a common complication of myocardial infarction. The most common type of aneurysm is a true aneurysm which forms after transmural infarction by gradual thinning and expanding of the scarred left ventricular wall. Its distinctive features are that of a large-mouthed sac containing all layers of ventricular wall. A rare type of aneurysm is the "false" or pseudoaneurysm of the left ventricle that develops from rupture of recently infarcted myocardial wall forming a localized haemopericardium confined by parietal pericardium. Pathologically, there is a small narrow-necked channel connecting the ventricle with a large sac consisting of only clot and fibrous pericardial tissue without any myocardial elements. Pseudoaneurysms are distinguished from the true variety by their marked tendency to rupture. Because surgical repair of a pseudoaneurysm is often successful, it is important to make the diagnosis of this entity as early as possible. Two-dimensional echocardiography in combination with Doppler-flow is the mainstay of clinical diagnosis. PMID- 2922863 TI - [Mentally ill homeless persons]. AB - Homelessness is a social problem but it is frequently associated with other problems connected with health. Abuse of illegal and legal intoxicants and severe mental illness among homeless persons make it increasingly difficult to provide support and help for homeless persons solely by means of social measures. Mentally ill homeless individuals are frequently well known both by the social authorities and by the staff of psychiatric hospitals. They have frequently been offered the traditional forms of help and therapeutic measures traditionally employed without this resulting in "cure and stability" and they are frequently left to their own devices. Many of the mentally ill homeless persons have some form of addiction which renders their existence more difficult. Hostels and homes for care do not traditionally offer homes for this type of clientele but this may prove necessary. It will be necessary to provide new measures, e.g. domiciliary forms for this group but without a multidisciplinary therapeutic team and without cooperation between the social services and the health services this can scarcely prove successful. PMID- 2922864 TI - [Venereal diseases in children and sexual abuse]. AB - Sexual abuse in children is reported increasingly frequently. The abuse frequently comes to the attention of the authorities when the children present symptoms which raise the suspicion of sexual abuse. One of these symptoms may be sexually transmitted disease in the child. Previously, there was a tendency to accept the possibility that sexually transmitted disease in children could be transmitted by other means than sexual contact, eg indirectly by infected bedclothes and toilet articles. Where gonorrhoea is concerned, no documentation exists in the literature for non-sexual infection in children. Condylomata acuminata are caused by infection with the human papilloma virus and may possibly infect children by non-sexual contact in rare instances but, in the majority of cases, meticulous investigation of the surroundings of the children will raise the suspicion of sexual abuse as the cause of the infection. The case history of gonococcal vulvo-vaginitis in a girl aged 23 months were the source of infection could not be successfully proved is mentioned. Two case histories are reported concerning anal condylomata acuminata in a girl aged nine years who had been sexually abused and a girl aged 25 months where there was a strong suspicion of sexual abuse but where the source of infection remained unknown. On the basis of literature from recent years and the case histories reported here, it is concluded that all gonococcal infections in children must be regarded as being sexually transmitted and these should, therefore, be reported to the social authorities. In addition, all children with ano-genital condylomata acuminata should be investigated meticulously for sexual abuse and be reported to the social authorities, if the suspicion is well founded. PMID- 2922865 TI - [The value of routine check-ups of patients after radical surgery of colonic cancer or rectal cancer]. AB - In this retrospective study, the efficiency of the postoperative follow-up regimen was evaluated in patients, radically operated for cancer of the colon or cancer of the rectum. The follow-up regimen consisted of clinical examination, including sigmoidoscopy every six months, supplemented by an X-ray of the colon every year. Two-hundred and eighty-nine patients were included in the study. Twenty-three local recurrences and 19 new malignant tumors were diagnosed 20 and 13 months (mean) after the primary operation, respectively. About one third of the local recurrences and half of the new malignant tumors were diagnosed at the planned follow-ups. Among these patients, a significantly higher success rate as regards radical operation was observed at the second operation. IN CONCLUSION: more frequent follow-ups during the first two years after the primary operation are recommended in order to improve early diagnosis. PMID- 2922866 TI - [Peritonitis in continuous ambulatory peritoneal dialysis. Experiences after 7 years]. AB - A retrospective study of CAPD-related peritonitis revealed a frequency of 1.7 episodes per treatment year among 121 patients during a period of 7 years. Life table methodology estimated a 44% probability of still remaining peritonitis-free after six months on CAPD, with no differences between subgroup populations according to sex, age (younger/older than 60 years) and primary disease (diabetic/non-diabetic). A marked improvement in probability of remaining peritonitis-free was evident in the last calendar period (1983-86). The predominant etiological microorganisms in peritonitis episodes were staphylococci. In 25% of the episodes, no microorganism could be isolated. One patient died from peritonitis; lethality 0.7% per year. Ten patients (8%) were transferred from CAPD because of either repeated episodes of peritonitis or a single complicated episode. PMID- 2922867 TI - [Carcinoma of the urachus]. AB - The urachus is an embryological structure originating from the allantois and situated in Retzius' space. Neoplasms originating from the urachus are very rare. They become clinically manifest late in the course of the disease. Deformation of the apex of the bladder and supravesical calcifications are described as radiological findings but these are of limited diagnostic value and should be supplemented by ultrasonic scanning, computed tomography and possibly by magnetic resonance scanning which will provide information about the extent of the disease. The final diagnosis is based on the macroscopic findings and the macroscopic picture. Three cases representing various aspects of the disease are presented. Treatment consists of en bloc resection in the form of partial cystectomy and excision of the tissue in Retzius' space and the umbilicus. The results are, however, disappointing as the five-year survival rates in the majority of materials do not exceed 10%. Irradiation is of doubtful value and chemotherapy is scarcely of value in the treatment. PMID- 2922868 TI - [Laser treatment of penile cancer]. AB - The treatment of localized penile cancer has hitherto been surgical amputation of the penis. In our 12 cases, tumorectomy was performed by CO2 or ND:YAG-laser radiation with minimal tissue ablation. Local recurrences occurred and the patients must be followed regularly in the outpatient clinic. The recurrences were treated by repeated laser radiation. No patients died of penile cancer during a mean observation of 16 months (range 3-50). Laser tumorectomy has definitive therapeutic advantages compared with penile amputation, because the result is acceptable for the patient and his micturition and sexual life are not altered. PMID- 2922870 TI - [Ride-on rotary motor mowers--a new mechanism of injury. Home accidents]. AB - A hand injury caused by a ridding-on rotary motor mower is described. The injury was caused by a piece of wire caught by the rotar of the machine which projected and rotated from under the safety guard. This mechanism of injury is possible on account of the relatively large dimensions of the riding-on rotory motor mower. The user had climbed down from the machine to remove objects lying close to the motor mower and was hit on the dorsum of the left hand. He sustained severe traumatic lesions of the first and third fingers and traumatic amputation of the second finger corresponding to the distal phalynx. The authors suggest that a "dead man's grib" which acts via weight bearing on the driver's seat of the machine should be made legally compulsory in Denmark when the new safety measures for rotory motor mowers are drawn up. PMID- 2922869 TI - [Pulmonary hypertension in children treated with ventriculo-atrial shunt in hydrocephalus]. AB - Four infants treated with ventriculo-atrial shunt for hydrocephalus developed sudden pulmonary hypertension, several years after the first operation. All infants died in spite of replacement of the distal shunt and AK treatment. At necropsy, old microemboli were found in the small lung vessels in two infants whereas the two other infants were suspected of having the same lesions from clinical investigations. The overall frequency for this complication was estimated to be 6.7% (95% CI 1.4-14.3%). PMID- 2922871 TI - [Carcinoid syndrome misinterpreted as an allergic reaction]. AB - A case of the carcinoid syndrome in a woman aged 65 years is reviewed. The condition was initially interpreted and treated as allergy. The carcinoid syndrome should be borne in mind in cases of recently-developed allergy in elderly patients. PMID- 2922872 TI - [Life-threatening hypokalemia during a weight reducing regimen in a woman with hypertension treated with diuretics]. AB - A case of hypokalaemia and metabolic alkalosis precipitated by a self-composed slimming diet in a woman treated with diuretics is presented. Cardiac stimulation and respirator treatment were required in addition to electrolyte therapy. Patients treated with diuretics should be warned against starting slimming cures without simultaneous frequent control of serum potassium. PMID- 2922873 TI - [Primary liver cancer in Denmark 1943-1985. Cancer statistics 24]. PMID- 2922874 TI - [Introduction to the challenging of the authoritative role of the physician. Interview by Asger Thomsen]. PMID- 2922875 TI - [Continuing education of medical specialists at the National Hospital]. PMID- 2922876 TI - [First year of the Board of Ethics]. PMID- 2922877 TI - [The disappointed patient and the burned-out physician]. PMID- 2922878 TI - [Social factors are of significance in giving birth to children with low birth weight]. PMID- 2922879 TI - Ultrasonically induced disruption and hemolysis of vitreous hemorrhages. AB - High-intensity focused ultrasound was used to insonify simulated vitreous hemorrhages in two in vitro models and one in vivo animal model. Histopathologic evaluation of the treatment effect was performed with light and electron microscopy. Ultrasonic parameters resulting in histopathologically proven disruption and hemolysis of intravitreal blood were investigated. Most important in obtaining this effect were the temporal average acoustic power and pulse repetition rate of the applied ultrasonic beam. Accurate positioning of the therapeutic beam and visualization of internal spatio-temporal response patterns in the blood during insonification were monitored via simultaneous diagnostic B mode imaging. Results suggested that high-intensity focused ultrasound might facilitate the two major mechanisms involved in the natural resorption process of vitreous hemorrhages namely hemolysis and surface-dependent phagocytosis. PMID- 2922880 TI - Ultrasound-induced damage of veins in pig ears, as revealed by scanning electron microscopy. AB - Pig ear veins have been treated in situ with ultrasound at a frequency of 750 kHz and intensity of 1.5 W cm-2 (spatial average) during which the temperature in the surrounding tissues rose to 52-54 degrees C. The veins were examined by scanning electron microscopy. Gaps developed between the endothelial cells, which showed many fine perforations in their membranes. Extensive blood clots were observed in which erythrocytes had become more spherical and showed damaged membranes. Effects on membranes were also found with HeLa cells heated to 50 degrees C, and have been previously described by others in heat-treated blood vessels. PMID- 2922881 TI - Investigation of cavitation in flowing media by lithotripter shock waves both in vitro and in vivo. AB - Cavitation produced by lithotripter shock waves was characterized in vitro in water and blood, and in vivo in aortic blood by means of a 1.6 MHz resonant bubble detector. This system was readily able to detect bubbles resulting from shock-wave induced cavitation in both water and blood flowing through plastic tubes in vitro, and even in blood pumped by the heart through a plastic arterio venous shunt. However, this system was unable to detect evidence of shock-wave induced cavitational activity occurring within the intact vascular systems of dogs in vivo. PMID- 2922882 TI - Cavitation induced by asymmetric, distorted pulses of ultrasound: a biological test. AB - Prediction of the response of gaseous microbubbles to ultrasonic waves is complicated by the finite-amplitude distortion associated with large amplitude acoustic fields. Typical finite-amplitude pulses in medical applications consist of a sharp positive spike followed by a smaller, slowly varying negative pressure. In previous theoretical studies it was found that: (a) the peak positive pressure is a very poor index of bubble response; (b) the peak-negative pressure typically underestimates the bubble response; (c) a better predictor of bubble response is the pressure amplitude of the fundamental in a Fourier series expansion of the distorted pulse. It is reported here that the killing of Drosophila larvae exposed to pulsed, symmetric, sinusoidal fields and to pulsed, asymmetric, distorted fields is consistent with these predictions. PMID- 2922883 TI - An explanation for the decrease in cell lysis in a rotating tube with increasing ultrasound intensity. AB - Previous observations indicate that for in vitro mammalian cells insonated in rotating test tube the amount of cell lysis initially increases to some maximum and then decreases with further increase in ultrasound exposure. The results of the present investigation support the postulate that the reduction in cell lysis with increase in ultrasound intensity is related to the development of an ultrasonically induced "cloud" of bubbles in the fluid between the transducer and test tube; these bubbles mitigate against acoustic transmission thus reducing cell lysis in the insonated test tube. PMID- 2922884 TI - A second order approximation in the Doppler equation. PMID- 2922885 TI - The Doppler shift and speed of sound in blood. PMID- 2922886 TI - The in vitro effect of electromagnetically generated shock waves (Lithostar) on the Dunning R3327 PAT-2 rat prostatic cancer cell-line. A potentiating effect on the in vitro cytotoxicity of vinblastin. AB - High energy shock wave lithotripsy has proven to be an effective tool in the management of renal calculi. The effects of electrohydraulically generated high energy shock waves (HESW) on tumor cells were described only recently. Here we present data on the experimental design for treatment of tumor cells, using electromagnetically generated shock waves. The determination of the focal area, in which pressures are at least 50% of the maximum pressure, appeared to be essential. In vitro HESW treatment resulted in a dose dependant anti proliferative effect on Dunning R-3327 PAT-2 rat prostate cancer subline, determined by temporal growth curve analysis after plating of treated cells in soft agar. Furthermore, it was shown that HESW treatment had a potentiating effect on Vinblastin treatment. The combination of HESW with Vinblastin appeared to have an additive in vitro anti-proliferative effect on PAT-2 prostatic cancer cells. PMID- 2922887 TI - Cyclosporine A impairs wound healing of ureterocystoneostomy in rats. Scanning electron microscopic examination. AB - The effect of cyclosporine A (CsA), an immunosuppressive agent used in transplantation, on wound healing following microsurgical neoimplantation of a ureter in the bladder of 63 SIV ZUR rats was examined morphologically using the light and scanning electron microscopes and functionally by radiography. Following ureterocystoneostomy (UCN) on the right side, the animals in Group I (control group) received 1.0 ml CsA solvent (0.1 g ethanol and 0.3 g intralipid) per day. Group II received 12.5 mg/kg/day CsA and Group III 17.5 mg/kg/day CsA. All drugs were administered i.p. A third of the animals in each group were reoperated 7, 14 or 28 days after UCN. At these time intervals, there were no radiologically demonstrable differences in the operated side. Examination under the scanning electron microscope indicated delayed restitution of epithelium in the bladder for rats which had received CsA as compared to the control group. In the area of the UCN, CsA caused dose-independent retardation of the regenerative hyperplasia associated with wound healing (Group I: max. 7 days after UCN: Group II and Group III, max. 14 days after UCN). Hyperplastic areas had ropy microridges and uniform short microvilli. Where the hyperplasia exhibited nodular and papillary formation, also histologically more evident under CsA, occasional epithelial cells had pleomorphic microvilli on their luminal surface. Unlike other known premalignant changes of this kind, the frequent occurrence of pleomorphic microvilli under CsA was reversible. In general, CsA led to dose unrelated protraction of UCN wound healing with no lasting functional disturbance in rats. PMID- 2922888 TI - Cyclosporine (Sandimmune) and wound healing. PMID- 2922889 TI - Interactive computerized morphometric analysis for the differential diagnosis between dysplasia and well differentiated adenocarcinoma of the prostate. AB - To distinguish prostatic dysplasia (or adenosis) from well differentiated adenocarcinoma on transrectal needle biopsy, a morphometric study was conducted on 20 cases of adenosis and 20 cases of well differentiated adenocarcinoma of the prostate. About 100 cells for each patient were analyzed by means of a computerized image analyzer, and mean nuclear diameter, mean nuclear area, mean form factor and number of cells in eight classes of nuclear diameter were studied. The best predictors of malignancy (evaluated by means of Receiver Operating Characteristics curves) were mean nuclear area greater than 28 mu2, presence of more than 5% of cells with nuclear diameter greater than 6.15 mu, and mean nuclear diameter greater than 5 mu. Using these diagnostic criteria the probability of malignancy for a positive specimen rises from 14% (pre-test) to 75% (post-test). PMID- 2922890 TI - Serum-Zn-levels in prostatic cancer. AB - Zinc in serum of both patients with prostatic carcinoma and men without prostatic cancer was analyzed by flame atomic absorption spectrometry (FAAS). No significant differences were found between the group with prostatic carcinoma without metastasis and the group used for comparison. The Zn level in serum of patients with both prostatic carcinoma and metastases was decreased in comparison to the other groups. A decrease in the Zn concentration was also found for men without metastases after orchiectomy and hormone therapy. PMID- 2922892 TI - Efficient storage of urodynamic signals by computer: application of FAN adaptive sampling. AB - Digital storage of urodynamic signals such as detrusor pressure and flowrate at a sufficiently high sampling rate (10 samples per second) to allow subsequent analysis requires considerable computer memory. A procedure for compressing these data by deleting redundant samples (the fan method of adaptive sampling) was tested. The method allows a flexible adaptation to specific hardware and a compromise between storage requirements and accuracy. In this study the number of samples required for adequate reconstruction of the detrusor pressure signal could be varied from 80% to 4% of the original number of samples by varying the average difference between reconstructed and original signal from 0.01 to 2 cm H2O. Fast components of the measurements (for example cough peaks) which were lost if a lower sampling rate or averaging was used to obtain equally low storage requirements were unaffected by this compression technique. PMID- 2922891 TI - Immunological aspects of intravesical administration of Bacillus Calmette-Guerin (BCG) in the guinea pig. AB - The only form of effective immunotherapy for human cancer is the intravesical administration of BCG in the treatment of superficial bladder tumors. In this study BCG was administered intravesically (once a week for six consecutive weeks) in guinea pigs to investigate the immune response. Both specific immune responses against BCG itself and nonspecific immune responses such as leukocyte subset distribution, mitogenic (ConA, PHA, LPS) lymphocyte stimulation and spontaneous cytotoxic (NK and LAK cell) activity were determined in the regional draining (iliac) lymph node and in the spleen. The PPD skin test became positive after the fourth intravesical instillation of BCG when 1 X 10(5) culturable particles or higher dosages of BCG were administered. A low dose of 1 X 10(3) c.p. of BCG induced a positive PPD skin reaction in 2 of 4 animals after six BCG instillations. After six BCG instillation BCG immune lymphocytes were present both in the iliac lymph nodes and in the spleen. No differences in mitogenic responses to ConA, PHA and LPS were observed in iliac lymph nodes or the spleen between placebo or BCG treated animals. In the regional iliac lymph nodes a significantly increased number of leukocytes was present. These lymph node cells showed a significant increase in the expression of MHC class II (Ia) immune response antigen on their surface. In the spleen no differences were observed after BCG administration regarding the number of cells present and in terms of the Ia antigen expression of the leukocytes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2922893 TI - High energy shock waves do not affect either primary tumor growth or metastasis of prostate carcinoma, R3327-MatLyLu. AB - We investigated the possibility that extracorporeal high energy shock wave (HESW) treatment of solid tumors increased metastatic tumor cell spread using a rapidly metastasising rat prostate tumor variant (R3327-MatLyLu). Volume of HESW treated primary tumor, the volume of metastatic lymph nodes and the number of lung tumor nodules formed were compared with values in untreated control rats. HESW treatment resulted in marked hemorrhage and readily visible hematoma at the focal point of treatment. Tumor histology directly after treatment showed extravascular blood cells due to breakage of blood vessels. Contrary to previous reports we could not observe a delay in tumor growth rate in either small or medium sized tumors. More importantly the extent of metastatic spread was not influenced by HESW treatment. PMID- 2922894 TI - [Microcomputer systems in urology: hardware--mole's hole or useful equipment?]. AB - The basic concepts and elements of micro- and minicomputer hardware components frequently used in urology are described. For advanced users, the details and trends are discussed in more detail. The interdependence of hardware and operating systems is emphasized. In addition, a method for the evaluation of personal computer performance is presented. Finally, proposals are made concerning purchasing procedures and selection criteria. PMID- 2922895 TI - [The effect of mineral water containing calcium on supersaturation of urine with calcium oxalate]. AB - The influence of mineral waters with different calcium content on the urine composition was investigated. Twelve healthy male test persons were housed for 3 x 24 h (once a week) in a climatic chamber under constant resting conditions. The standardized food intake was distributed equally over 24 h. Six 4-h urine samples were collected and chemically analyzed to study the risk of stone formation. The total amount of mineral water (Staatl. Fachingen or Bad Wildunger Helenenquelle) or of tapwater was administered in three portions (700 ml at 9.00, 350 ml at 13.00, 350 ml at 17.00). After mineral water intake, the calcium concentration in the urine was slightly higher. However, the more highly mineralized water caused a significant increase in the urinary magnesium concentration, which persisted into the night. The citrate concentration was increased as a result of alkalization of the urine. After mineral water intake the oxalate excretion was slightly (but not significantly) higher. However, no increased risk of calcium oxalate stone formation was seen when different supersaturation ratios were used as the basis of calculation. In a second study, further 12 volunteers of both sexes were given an oxalate-rich standard meal and 500 ml of the test waters in addition. The urine oxalate concentration was measured hourly for 6 h after the meal, and the total oxalate excretion was calculated. The renal oxalate excretion after mineral water intake was significantly reduced compared with tapwater controls. This effect may be caused by intestinal binding of oxalate by calcium and indicates a further lowering of the risk of calcium oxalate crystallization. PMID- 2922896 TI - [Risk indicators of urinary calculus formation: value of oxalate and citrate excretion in comparison with the oxalate tolerance value]. AB - Several methods for the measurement of crystallization conditions in urine, the so-called whole urine systems, have recently been of considerable interest in urolithiasis research. The diagnostic accuracy of the oxalate tolerance value (OTV) was therefore compared with the daily excretion of oxalate and citrate in normal persons and patients with urinary calculi. With the aid of the oxalate/citrate ratio, 77% of the patients could be classified correctly. After standardization of the experimental conditions (24-h urine sample, constant pH value, consideration of endogenous oxalate) we succeeded in correctly classifying 82% of patients using the OTV. These results favour the introduction of the OTV as a clinical chemical tool for the follow-up of patients with urinary calculi and for the screening of normal persons at risk. PMID- 2922897 TI - [Polychemotherapy using the M-VEC protocol (methotrexate, vinblastine, epirubicin, cisplatin) in advanced urinary bladder cancer--effectiveness and toxicity]. AB - We report on preliminary experience with a modified M-VAC (methotrexate, vinblastine, adriamycin and cisplatin) regimen in which adriamycin was replaced by the less toxic 4-epirubicin at equal doses (M-VEC). This study includes 58 patients suffering from advanced bladder cancer, with a minimum observation time of 12 months; each patient received at least two courses of M-VEC (mean follow-up 22 months, average 3.9 cycles). Most (22; 37.9%) of the tumors were T3-4 NO MO; 20 (34.4%) were T3-4 N1-2 MO; and 16 (27.7%) were T3-4 NO-2 M1. Microscopically, 52 (89.6%) were pure transitional cell carcinoma, 5 were (8.6%) squamous cell/carcinomatous transformation; 1 (1.8%) sarcoma was found. Chemotherapy was given as palliative treatment in 34 (58.6%) patients, as neo-adjuvant therapy in 19 (32.8%) cases and as adjuvant therapy in 5 (8.6%) patients. The overall response rate was 72.3% (CR = 51.7%), with a mean duration of response of 18+ months. The disease-free survival so far amounts to 24/58 (41.4%). Squamous cell carcinoma does not respond to M-VEC. Locally advanced bladder cancer (T3-4 NO-2 MO) responds significantly better than metastatic (M1) disease (78.5% vs 56.2%), resulting in an increased survival rate (57% versus 12.5%) after 22 months. The toxicity of M-VEC is considerably lower than has been reported for other regimens (M-VAC, CMV, CM). The toxic effects included mucositis (3%), nadir sepsis (2.4%) and drug-related death (2.4%). PMID- 2922898 TI - [BCG in reflux]. AB - Nine patients with radiologically proven vesicorenal reflux (3 bilateral, 4 unilateral, 2 with unilateral double-J stents) received intravesical bacillus Calmette-Guerin (BCG) as prophylactic treatment for recurrent superficial bladder carcinoma. One patient with a double-J stent suffered an attack of high fever, probably following obstruction of the stent. All other patients tolerated one cycle or two cycles (5 of 9 patients) of 6 weekly instillations without significant complications. There was no increased toxicity compared with a control group of 39 patients without reflux who were receiving BCG. Topical intravesical immunotherapy with BCG in patients with vesicorenal reflux can be given without a rise in the complication rate; indeed, in view of the multifocal appearance of urothelial carcinoma in this subgroup, this type of therapy even appears to be desirable. PMID- 2922899 TI - [Differential diagnosis of acute scrotum by nuclear medicine study]. AB - Sixty-four patients with acute scrotal pain were examined by radionuclide scrotal scanning. We compared clinical, surgical and radionuclide findings. The scrotal scanning is a rapid, non invasive and painless examination with high accuracy in inflammatory disease. But two falsely negative scans in acute testicular torsion warn against this simple method. Torsion of the appendix testis were not recognized by scanning. PMID- 2922901 TI - The ins and outs of cash flow. PMID- 2922900 TI - [Pheochromocytoma and adrenal gland hyperplasia in a remaining atrophic kidney]. AB - We report the not-yet-published case of a renal cell carcinoma in an atrophic kidney in combination with ipsilateral pheochromocytoma and adrenal cortex hyperplasia. The cause of the adrenal cortex hyperplasia was found to be the result of a reaction to the accompanying adaptation hyperplasia. PMID- 2922903 TI - Development of a coding system for recording clinical findings in farm animal practice. AB - A coding system was developed for recording veterinary information in the University of Liverpool farm animal practice. Existing coding systems were found to be unsuitable for use on a microcomputer in a veterinary practice. A number of new coding formats were developed and tried. The need to record varying detail, to analyse data and to enter data quickly resulted in biaxial hierarchical codes. These are used in an automated coding system to record all veterinary and reproduction information in the practice. PMID- 2922902 TI - Comparison of two early season anthelmintic programmes on a commercial beef farm. AB - Two early season suppressive anthelmintic programmes, ivermectin given three, eight and 13 weeks after turn out and a morantel sustained release bolus administered at turn out, were compared on a commercial farm. The morantel treated cattle grew significantly faster than the ivermectin treated group during the period of treatment, on average at 0.80 kg/day compared with 0.71 kg/day (P less than 0.01). In the second half of the grazing season (13 to 25 weeks after turn out) the ivermectin treated group grew faster than the morantel treated group although the difference was not statistically significant. Over the entire grazing season there was no significant difference in average growth rate between the morantel treated group which grew at 0.80 kg/day and the ivermectin treated group which grew at 0.77 kg/day. These results were related to pasture larval counts, faecal egg counts and plasma pepsinogen levels throughout the grazing period. It was concluded that the morantel sustained release bolus allowed growing cattle to reach their production potential during the period of treatment. However, its efficacy in maintaining production throughout the grazing season was reduced by the 90 day treatment period which failed to give the level of control of gastrointestinal nematode parasites achieved by the 105 day period of treatment in the ivermectin programme. PMID- 2922904 TI - Multifocal symmetrical encephalopathy in Simmental calves. PMID- 2922905 TI - Evidence for sheep as a maintenance host for Leptospira interrogans serovar hardjo. PMID- 2922906 TI - Elaphostrongylus cervi in Danish wild red deer (Cervus elaphus). PMID- 2922908 TI - Veterinary remuneration. PMID- 2922907 TI - Riley recommendations. PMID- 2922909 TI - Quality assessment scheme. PMID- 2922910 TI - Computers in veterinary practice. PMID- 2922911 TI - Electrolytes and reproductive hormone concentrations in maternal plasma and fetal fluids of dairy cows with hydrops. AB - Electrolytes, metabolites, cortisol and reproductive hormones were measured in maternal plasma taken at least twice daily from three cases of bovine hydrops before, during and after parturition induced by dexamethasone or prostaglandin. Caesarean operations were required for two of the cases. Maternal plasma electrolytes remained within the normal range, but average potassium and creatinine concentrations were higher (9.2 and 0.68 mmol/litre, respectively) than normal (4.7 and 0.42 mmol/litre) in samples of amniotic fluid obtained at calving. Sodium (100 mmol/litre) and chloride (67 mmol/litre) in allantoic fluid were also higher than normal (53 and 20 mmol/litre, respectively). Conversely, creatinine concentrations were lower than normal in allantoic fluid (2.2 vs 13.8 mmol/litre). Oestradiol concentrations were lower than normal in maternal plasma (ranges: less than 20 to 140 pg/ml vs 30 to 440 pg/ml); maximum prostaglandin F metabolite (PGFM) concentrations were slightly elevated (ranges 1.1 to 2.0 ng/ml vs 0.4 to 0.9 ng/ml). Progesterone and cortisol concentrations remained within the normal range; the latter hormone increased markedly in parallel with raised PGFM concentrations. In two cases, the concentrations of reproductive hormones tended to be lower in the amniotic fluid than in the allantoic fluid. For example, progesterone concentrations were 42.8 and 14.9 ng/ml in the amniotic fluids vs 64.2 and 29.8 ng/ml in the allantoic fluids of the two cows; PGFM concentrations were 27.7 and 4.3 ng/ml vs 34.6 and 5.0 ng/ml, and oestradiol concentrations were 1.5 and 3.5 ng/ml vs 1.1 and 6.4 ng/ml in the two fluids, respectively. PMID- 2922912 TI - Stress resistant and stress susceptible landrace pigs: comparison of blood variables after exposure to halothane or exercise on a treadmill. AB - Stress susceptible pigs develop pale, soft, exudative pork as a consequence of exposure to natural stress or exposure to halothane. Hyperstimulation of glycolysis is a major component of the stress reaction. Whether natural and artificial stress have other similarities was investigated by exposing pigs to halothane or to physical exercise, and measuring their blood composition. There were many similarities between the two groups but the significant differences suggest that although both halothane and exercise induce glycolysis, the mechanisms involved are different. PMID- 2922913 TI - An intersex horse with X chromosome trisomy. AB - An X-trisomy has been detected in an intersexuality Spanish-bred horse by using G and C-banding methods. The external characteristics and the behavioural and physiological irregularities of the horse are described. This is the first time that an association between an X-trisomy and a case of intersexuality has been reported in any domestic animal. PMID- 2922914 TI - Microbiological and pathological evaluation of vaccination against naturally occurring caprine pasteurellosis. PMID- 2922915 TI - Riley recommendations. PMID- 2922916 TI - Acute nephropathy in young lambs. PMID- 2922917 TI - Listerial abortion in the bitch. PMID- 2922918 TI - Withdrawal of mitotane. PMID- 2922920 TI - 'What's the BVA doing about it?'. PMID- 2922919 TI - Veterinary remuneration. PMID- 2922921 TI - Bovine fascioliasis: a need to revisit control strategy. PMID- 2922922 TI - Relationship between virulence of Chlamydia psittaci strains and establishment of persistent infection of McCoy cells. AB - The pathogenicity of chlamydial strains for their natural hosts and their ability to induce persistent infections in McCoy cells were compared. Both virulent and avirulent strains persistently infected McCoy cells, but the appearance of the cell culture varied between strains. Avirulent strains induced completely inapparent persistent infection (infection Type 1), while with invasive strains the culture alternated between periods of cell multiplication and periods of extensive cytopathic change (infection Type 2). The virulence of virulent strains was not attenuated, even after 6 months of culture, but after 2 or 3 months some avirulent strains produced infection Type 2 and became invasive for mice and abortive for ewes. This variation of virulence was accompanied by a modification of protein patterns. PMID- 2922923 TI - Yellow fever virus proteins NS2A, NS2B, and NS4B: identification and partial N terminal amino acid sequence analysis. AB - A series of fusion proteins corresponding to the hydrophobic ns2 and ns4 regions of yellow fever virus (YF) were generated in Escherichia coli using trpE fusion vectors. Antisera to ns2 and ns4 region fusion proteins recognize virus-specific proteins of 15 and 27 kDa, respectively. N-terminal amino acid sequence analysis of the 27-kDa protein indicates that the N-terminus of YF NS4B immediately follows a signalase-like cleavage site. Additional sequence data generated by microsequence analysis of labeled proteins immunoprecipitated with mouse hyperimmune antisera have identified the 15-kDa protein as NS2B and an additional 20-kDa viral protein as NS2A. Comparison of the sequences adjacent to the N termini of these viral proteins suggests that three distinct types of cleavage events are involved in processing the hydrophobic YF ns2 and ns4 regions. These include cleavage after a short side chain amino acid to generate the N-terminus of NS2A, cleavage after two arginine residues to produce the N-terminus of NS2B, and a cleavage site consistent with the specificity of signalase to generate the N-terminus of NS4B. Analysis of virus-specific protein patterns in several different mammalian cell lines and in Aedes albopictus cells suggests that the same cleavage sites are used in different hosts. These findings are discussed in relation to the processing of flavivirus polyproteins. PMID- 2922924 TI - Sequence analysis of the nucleocapsid protein gene of human coronavirus 229E. AB - Human coronaviruses are important human pathogens and have also been implicated in multiple sclerosis. To further understand the molecular biology of human coronavirus 229E (HCV-229E), molecular cloning and sequence analysis of the viral RNA have been initiated. Following established protocols, the 3'-terminal 1732 nucleotides of the genome were sequenced. A large open reading frame encodes a 389 amino acid protein of 43,366 Da, which is presumably the nucleocapsid protein. The predicted protein is similar in size, chemical properties, and amino acid sequence to the nucleocapsid proteins of other coronaviruses. This is especially evident when the sequence is compared with that of the antigenically related porcine transmissible gastroenteritis virus (TGEV), with which a region of 46% amino acid sequence homology was found. Hydropathy profiles revealed the existence of several conserved domains which could have functional significance. An intergenic consensus sequence precedes the 5'-end of the proposed nucleocapsid protein gene. The consensus sequence is present in other coronaviruses and has been proposed as the site of binding of the leader sequence for mRNA transcriptional start. This region was also examined by primer extension analysis of mRNAs, which identified a 60-nucleotide leader sequence. The 3'-noncoding region of the genome contains an 11-nucleotide sequence, which is relatively conserved throughout the Coronavirus family and lends support to the theory that this region is important for the replication of negative-strand RNA. PMID- 2922925 TI - The sequences of the reovirus serotype 1, 2, and 3 L1 genome segments and analysis of the mode of divergence of the reovirus serotypes. AB - We report the sequence of the L1 genome segment of reovirus serotype 3 strain Dearing, which encodes the minor core component protein lambda 3. It is 3854 bp long, with a long open reading frame starting at position 19 that is 1267 codons long. Protein lambda 3 is not detectably related to any other protein, nor does it appear to possess motifs indicative of recognized specialized functions. We have also sequenced the L1 genome segments of reovirus serotypes 1 and 2. The serotype 1 and 3 L1 genome segments are extremely closely related; there are only 154 mismatches (4.1%), 80% of which are in third base codon positions, so that these two lambda 3 proteins are 98.3% related (only 22 mismatches out of 1267). The serotype 2 L1 genome segment is only 75% related to the serotype 1 and 3 genome segments, and the serotype 2 lambda 3 protein is 92% related to the serotype 1 and 3 lambda 3 proteins. We have also analyzed the divergence patterns by which the various reovirus genome segments evolved into the three serotype forms. It appears that serotype 2 separated from the serotype 1/3 precursor long before serotypes 1 and 3 themselves diverged. In all cases the third base codon positions in the various genome segments have diverged about 80% toward randomness. The first and second base codon positions have diverged much less and to varying degree, depending, presumably, on each protein's ability to accept changes without significant loss of function. For the separation into the serotype 1 and 3 forms, the extent of divergence of the various genome varies over a very wide range. The S1 genome segments have again diverged most extensively, the extent of divergence in the first, second, and third base codon positions being about 50, 35 and 75%, respectively. For seven other genome segments that we examined the extent of third base codon position divergence is 56, 53, 48, 29, 22, 13, and 6%, whereas first and second base codon position divergence ranges from no more than 6 to 2 and 3 to less than 1%, respectively. The most likely explanation of these patterns is that the separation of the various genome segments into the present-day serotype 1 and 3 associated forms occurred at different times during evolution, from progenitors that were genome segment reassortants with survival rates as high as or higher than those of homologous genome segment sets. PMID- 2922926 TI - Molecular cloning and analysis of the N5 neuraminidase subtype from an avian influenza virus. AB - The neuraminidase (NA) gene from the prototype N5 influenza virus, A/Shearwater/Australia/72, has been cloned and completely sequenced. An open reading frame of 1404 bp (468 amino acids) is flanked by 20-bp 5'- and 31-bp 3' untranslated regions. The deduced amino acid sequence of the N5 gene was compared with sequences from N2, N1, N7, N8, and N9 subtypes. One hundred thirteen amino acid residues (24%) are completely conserved across subtypes and include active site residues, cysteines, potential glycosylation sites, and certain glycines which suggests that these subtypes share a common ancestor and adopt the same 3-D conformation. Three groups can be assigned from amino acid homologies: (i) N5, N8, N1; (ii) N7, N9; and (iii) N2 where the percentage identity within groups is 55-68% and between groups is 40-46%, the N5-N8 pair bearing the closest identity (68%). Phylogenetic analysis suggests that these groups diverged concurrently. PMID- 2922927 TI - Organization of tomato bushy stunt virus genome: characterization of the coat protein gene and the 3' terminus. AB - We have synthesized cDNA clones of the genome of the cherry strain of tomato bushy stunt virus (TBSV-cherry) and have used them as hybridization probes to identify and position two 3' coterminal subgenomic RNAs of approximately 2.2 and 0.9 kilobases (kb) in length. The 5' termini of the two subgenomic RNAs have been mapped to positions located 2156 and 936 nucleotides respectively from the 3' terminus of the viral genome. The nucleotide sequence of cDNA clones encompassing the region of the genome containing both of the subgenomic RNAs has been determined. The sequence data indicate that two nested open reading frames (ORFs) occur in the most 3' proximal location on the genome suggesting that the 0.9-kb subgenomic RNA potentially encodes two polypeptides of 19,397 and 21,610 Da. Comparison of the amino acid sequence of a potential translation product of 41,024 Da encoded by the first ORF of the 2.2-kb subgenomic RNA with the published capsid protein amino acid sequence of the BS-3 strain of TBSV indicates that the 2.2-kb subgenomic RNA encodes the capsid protein. The TBSV coat protein cistron is located internally on the genome and thus its genetic organization differs from that reported for most other small, spherical viruses with monopartite genomes. Amino acid sequence comparisons of analogous regions of the cucumber necrosis virus (CNV) genome confirms a close relationship between the viruses. PMID- 2922928 TI - Sequence analysis of the mumps virus mRNA encoding the P protein. AB - The nucleotide sequence of the mumps virus phospho- or polymerase-associated (P) protein mRNA has been determined by sequencing a full-length cDNA clone and confirmed by partially sequencing the mRNA and the genome. The mRNA contains 1311 nucleotides excluding the poly(A) and encodes a protein of 390 amino acids with a calculated molecular weight of 41,574. Three small polypeptides were seen in in vitro translation of viral mRNA and hybrid-selected P mRNA, possibly representing internal initiation in the same reading frame of the P protein. A second overlapping reading frame is predicted from the sequence which has a capacity to code for two polypeptides of 56 and 34 amino acids, respectively. Whether these two polypeptides are expressed in infected cells is not known. Comparison of the P protein sequence with that of Sendai virus, measles virus, parainfluenza virus type 3, and canine distemper virus (CDV) showed no distinct homology but comparison with the P protein of Newcastle disease virus (NDV) showed 25.6% homology. PMID- 2922929 TI - Segment W of Campoletis sonorensis virus: expression, gene products, and organization. AB - Campoletis sonorensis virus (CsV, Polydnaviridae) is a segmented double-stranded DNA virus which has an apparently symbiotic relationship with the parasitic wasp, Campoletis sonorensis. CsV replicates in the oviducts of the parasitic wasp and is injected into the wasp's host, Heliothis virescens (Lepidoptera; Noctuiidae), during oviposition. In the parasitized lepidopteran host, the virus has a dramatic effect on host physiology and viral gene products are believed to play an essential role in the survival of the parasitic wasp's egg and larva. In the current study, we used Northern blot analyses to examine expression from segment W in the parasitized host and in the parasitic wasp. Segment W hybridized primarily to two relatively abundant mRNAs (1.6 and 1.0 kb) from the parasitized host. These 1.6- and 1.0-kb mRNAs, which were previously shown to be transcribed from two closely related genes (WHv1 and WHv2) on segment W (G. W. Blissard, O. P. Smith, and M. D. Summers, 1987, Virology 160, 120-134) increased in relative abundance between 2 and 24 hr postparasitization (pp) and were detected throughout parasitization (8 days). To study the proteins encoded by these closely related genes, the open reading frame from each of the related genes was cloned into a baculovirus expression vector. By pulse labeling in the presence and absence of tunicamycin, we examined secretion and glycosylation of these CsV proteins in infected lepidopteran cells (Spodoptera frugiperda). Expression of segment W in the oviducts of the female wasp was also examined. Segment W hybridized to at least five CsV mRNAs on Northern blots of poly(A) mRNA from C. sonorensis oviducts. To identify specific CsV mRNAs and map putative viral genes expressed in wasp oviduct tissues, segment W was used to screen a cDNA library of C. sonorensis oviduct mRNAs. Three cDNAs were used to identify CsV mRNAs by Northern blot analyses and to map the locations of three putative CsV genes on segment W. Cross-hybridization within the CsV genome was examined with cloned segment W and with the three cloned cDNAs. PMID- 2922930 TI - Extrahepatic replication of woodchuck hepatitis virus in chronic infection. AB - We describe studies of woodchuck hepatitis virus nucleic acids in liver and other tissues of chronically infected woodchucks, using Southern and Northern blot hybridization techniques. Single-stranded and covalently closed circular replicative DNA molecules were distinguished from partly double-stranded virus genomes. In most animals the liver contained more virus than any other organ, but all extrahepatic organs studied (spleen, thymus, pancreas, and kidney) contained viral DNA and significant amounts of viral RNA. In the spleen, partly double stranded virus genomes were present at higher levels than in any other organ but liver, but nonetheless replicative intermediates were not detected. The observation of RNA transcripts in the absence of detectable covalently closed circular DNA template suggests that a small proportion of cells in extrahepatic tissues are infected with WHV. PMID- 2922931 TI - [Requests for chemical analysis: growth without end?]. AB - The number of analyses dealt within laboratory medicine increased from 1970 until the middle of the 80s by about 15% per annum in the German Federal Republic. The number of analyses in clinical chemistry, haematology, blood banking and haemostaseology have now reached a plateau. Because these analyses account for 85% of laboratory testing in big hospitals, the problems of rapid growth do not exist any longer. The single most important concern today is the spiralling cast of the remaining 15% of analyses, in the fields of serology, tumour diagnosis and monitoring, endocrinology, drug monitoring and microbiology. These investigations, which are rapidly increasing at the rate of about 15% annually, are mainly analyzed by means of the immunoassay technique. Immunoassays are very cost-intensive and, thus, current trends in laboratory medicine are characterized by an overproportional increase in costs with no foreseeable diminution in escalation. PMID- 2922932 TI - [IgE and IgG antibody response in patients with type I allergy to birch pollen]. AB - IgE and IgG antibody responses to birch pollen were investigated in sera derived from patients with type I allergy to birch pollen by means of immunoblotting. 56/58 patient sera contained IgE antibodies to a 17 kD pollen protein, recently designated as Bet v 1. In 33/58 patient sera no evidence was obtained for IgE antibodies to other pollen proteins than Bet v 1. However, in 25/58 sera, IgE antibodies reacting with 11 different allergens of 13, 15, 18, 27, 29, 32, 36, 39, 44, 57, 68 kD with an individual prevalence ranging from 1.7% to 17.2% were identified. All these IgE-binding proteins were also recognized by patients IgG. IgG responses to Bet v 1 were rather weak or lacking entirely, whereas in the case of the minor allergens pronounced IgG responses were observed. Samples from patients undergoing hyposensitization therapy showed an induction of anti-Bet v 1 IgG and a decrease in anti-Bet v 1 IgE upon treatment. These changes in antibody profiles to Bet v 1 did not correlate with the clinical benefit of the hyposensitization therapy. PMID- 2922933 TI - Labile disulfide bonds and free thiol groups in human IgG. IV. Use of the "sigma S" value for postoperative monitoring of gynaecological malignant tumors. AB - "sigma S" comprises both disulfide bonds reactive to dithionitrobenzoate, as well as free SH groups of serum immunoglobulin G. In 38 cases of invasive gynaecological tumors, the value of sigma S was ascertained to be 1.04 +/- 0.25 (mean +/- SD), which, in accordance with former results, differs significantly from the reference value of 1.51 +/- 0.36 (2 p less than 0.001). 14 days after surgery, at the latest, sigma S significantly increased to an average value of 1.33 +/- 0.26 (2p less than 0.001). This increase was apparently influenced by both the localisation, as well as by the completeness of removal of the tumors. Of 15 squamous cell carcinomas of the cervix uteri, 14 were radically removed and showed a highly significant postoperative increase in the sigma S value (2p less than 0.001). All of the 12 adenocarcinomas of the corpus uteri were totally removed and the sigma S increased significantly (2p = 0.05). Of 11 cystocarcinomas of the ovary, only 3 cases were completely operable. The remaining 8 cases had residual tumors with diameters greater than 5 cm. The postoperative increase in sigma S in these cases was not of statistical significance. PMID- 2922934 TI - [Changing physicians in general practice]. PMID- 2922935 TI - [The effectiveness of antimicrobial chemotherapy in patients with acute infection of the upper respiratory tract]. PMID- 2922936 TI - [A publication for the family physician]. PMID- 2922937 TI - [Acupuncture--a method in the treatment of vasomotor rhinitis]. PMID- 2922938 TI - Milk analysis for the iodine status of dairy cows. AB - Milk iodine analysis is a valuable tool in assessing the iodine intake of milk cows under quite different conditions. It can be used as a routine method of quality control for large areas, for the status of the cow, as well for the iodine intake of the population. Regarding the cow: from time to time samples of feed and blood should be available for checking how much of the milk iodine has passed through the body and has contributed to the iodine status. Regarding the population: all iodine in the milk is available for nutrition. PMID- 2922939 TI - [Serum and whole blood concentrations of fat and water soluble vitamins in normal persons and athletes]. AB - Water-and fat-soluble vitamins have a key function in many metabolic processes and are of special importance for athletes. The water-soluble vitamins thiamine, riboflavin and pyridoxine and the fat-soluble vitamins beta-carotene, retinol and alpha-tocopherol were determined by High-Pressure-Liquid-Chromatography (HPLC). The mean serum values in non athletes (ng/ml) were for thiamine 9.23 +/- 3.62, riboflavin 6.17 +/- 2.46 and pyridoxine 12.41 +/- 4.59; the blood values for thiamine 20.12 +/- 7.58, riboflavin 13.43 +/- 3.97 and pyridoxine 18.75 +/- 6.66. The mean values of the fat-soluble vitamins were for beta-carotene 3.76 +/- 252 micrograms/l, retinol 598 +/- 141 micrograms/l and alpha-tocopherol 12.6 +/- 2.9 mg/l. The values of athletes (of different sport disciplines) for the water soluble vitamins were much higher compared to the values found in non-athletes whereas the values for the fat-soluble vitamins were not much different. PMID- 2922940 TI - [The value of determining delta-aminolevulinic acid in urine (method II, East German occupational monitoring) as a screening procedure for the assessment of internal residues in occupational exposure to lead]. AB - For the purpose of supervising workers exposed to lead the ratio of blood lead is determined several times per year. The withdrawal of blood samples from the vein necessary for this purpose as well as the comparatively high analytic expense make it essential to revise, whether it is possible to give up the analysis of blood lead at least partially in favour of other diagnostic measures less affecting the worker. Our investigation gave evidence of the fact, that the validity of a screening test for evaluating the blood lead concentration on the basis of the determination of delta-aminolaevulinic acid in urine (method II, AB DDR; 2 nd morning urine) is insufficient. PMID- 2922941 TI - [Characterization of exposure to pollutants in spray painting industries using room air concentration values and an exposure test]. AB - Occupational-hygienic measurements of the interior air concentration had been performed in a large number of spray painting plants. The analyses stated that with most of the cases the exposition risk on varnishers is characterized by aerosol concentration and the concentration of lead and chromate in it. The concentrations of vapours of solvent mixtures are of subordinate importance. PMID- 2922942 TI - [The possible role of occupational factors in influencing the manifestation of idiopathic femur head necrosis]. AB - The idiopathic necrosis of the femoral head of adults is increasing. The disease appears in the age from 20 to 40 years and leads to the destruction of the femoral head. The final state is often a severe osteoarthrosis of the hip joint already in the efficient lifetime. The etiology of the idiopathic necrosis of the femoral head is not yet cleared up. There were only few information about possible professional factors. In a study the professional anamnesis of 153 patients were utilized. Thereby high portions of works with dynamic and static charges and expositions of vibrations were found. PMID- 2922943 TI - [Prevention of occupational and community health problems using Falisan Universal liquid caustic]. AB - Based on tests with Falisan-Universal fluid caustic the authors report on measuring results of laboratory tests and analyses of utilization. The air pollution caused by the active agent phenyl mercury acetate and the formulation remedy dimethylformamide is assessed. Conclusions are made for the caustic's application and for its tests. PMID- 2922944 TI - [Micromethods for the Widal reaction]. AB - Micro methods are described at the example of Salmonella and Yersinia-O-Widal and the Salmonella-H-Widal. The reaction is performed by micro titre plates with painted antigens. Basic Fuchsin had been used. Other antigen concentrations are partially required as to the tubule agglutination. The parallel comparison of the tubule and micro methods with test serum resulted in an important variation range of the tubule method. By subjective registration the rates may vary between 3 to 6 titre stages, same results in the micro method amount to 1 titre stage only. Thus by means of the micro method, the evidence of the Widal reaction is improved reducing at the same time expenses for material and work. PMID- 2922945 TI - [Patient attitudes as predictors of success in autogenic training]. AB - Therapy related patterns of attitudes are already traceable before starting autogenous training and can be considered to be predictors of therapeutic success. They make possible an approach to the differential indication of psychotherapy as situative variables in addition to the patients' habitual characteristics. Patients' who are successful in autogenous training can be described pretherapeutically by specific patterns of attitudes, which can be characterized by a low external locus of control (Krampen 1981) with rather little differentiated insight in the psychogenesis. PMID- 2922946 TI - [Cooperation between East Germany and Czechoslovakia in studying the effect of environmental pollution on school children]. AB - This report presents key outcomes of joint growth and development studies conducted in children permanently living in areas adversely affected by pollutants in air. Further attention is focussed on the evaluation of effects of some of the so-called compensatory measures applied in Czechoslovakia, namely a 3 week outdoor schooling organized for these children in the relatively clean recreational areas. The beneficial health effects of year's season and specifically of the spontaneous, active and sufficiently long outdoor exercise are documented in graphs. As it is pointed out in this context, children in the place of their permanent residence tend to have relative little exercise outdoor, may run an increased risk of exposure to indoor pollutants, and may suffer from passive smoking effects if their parents cannot refrain from smoking habits at home. PMID- 2922947 TI - [Epidemiologic study of indoor formaldehyde and nitric oxide pollution]. AB - The authors report on some selected results of an 87-pilot study, by means of which has been started to analyse the influence of formaldehyde, nitrogenous oxide and tobacco smoke on school children visiting 3. classes in old and new buildings in their schools and dwellings. PMID- 2922948 TI - [A passive sampler for simultaneous determination of formaldehyde and nitrogen dioxide in indoor air]. AB - The author demonstrates a diffusion passive collector for simultaneous determination of HCHO and NO2 of indoor air. The passive collector consists of a bottom-equipped glass tube, a shaped insertion of refined-steel wire netting (impregnated by triethanolamine) and a polyethylene cap sealing the opening. With an exposition period of 1 to 6 days, the pollutants HCHO and NO2 can be determined within a range of 10 to 400 micrograms/m3. After cleaning the collectors by chromium sulphuric acid, they can be used for any number you like. PMID- 2922949 TI - [Subcutaneous fat necroses, arthritis and vasculitis of small skin vessels in chronic pancreatitis]. AB - We describe an 42 year old patient suffering from chronic pancreatitis for 7 years who additionally developed subcutaneous fat necrosis, acute arthritis and erythema nodosum--like skin lesions. These symptoms associated with acute or chronic pancreatic disease represent a rare clinical entity. In this case the clinical course was rapidly progressive, resistant to therapy and further complicated by a vasculitic process. PMID- 2922950 TI - [German Association for the Study of the Liver. Abstracts 1989. Dusseldorf, 20-21 January 1989]. PMID- 2922951 TI - [Necrotizing panniculitis in pancreatitis]. AB - A 46-year old man developed subcutaneous fat necrosis of the right upper thigh in association with pancreatitis. The panniculitis established by biopsy resolved 4 years later. Subcutaneous nodular fat necrosis is a rare dermatological manifestation of pancreatitis or pancreas carcinoma which may be clinically indistinguishable from erythema nodosum. Biopsy of the skin lesion reveals a characteristic histological picture with necrotic fat cells surrounded by lymphocytes, histiocytes and plasmacells. PMID- 2922952 TI - [Validation of long-term ECG equipment]. PMID- 2922953 TI - [ST-segment analysis in long-term ECG: amplitude and phase response of various systems in comparison with standard ECG and their effect on true original reproduction of ST segment depression]. AB - Ambulatory ECG monitoring has been suggested as a method for the detection of transient myocardial ischemia. But it is still unclear how accurately ST-segment alterations can be detected with the different systems. Measurement of amplitude and phase response is a valid method to estimate the fidelity of reproduction of an ECG-signal. We investigated the direct-recording long-term ECG systems CardioData Mk4 with recorder PR3, CardioData Mk4 with Spacelabs recorder, DMI Eclipse with DMI Recorder, Reynolds Pathfinder II with Oxford replay PB2 and recorder MR-10 and Reynolds Pathfinder III with tracker in comparison to a standard ECG recorder Picker Schwarzer C6800. Amplitude vs frequency response curves were derived from input sinus waves ranging from 0.01 to 500 Hz. The phase response was measured with a phase-sensitive waveform at a frequency range from 0.05 to 10 Hz. To determine the distortion of the ST-segment on the actual ECG, we produced a standard PQRST-signal that was modified to provide flat ST-segment depressions from 0 to 0.5 mV at 0.05 mV increments. The low and high frequency cut-off of the amplitude response was found at 0.09 and 220 Hz with the standard ECG recorder. A phase shift of -30 degrees was detected at 0.07 Hz. ST-segment depressions of the test-ECG were reflected to the same extent. For the CardioData System, both cassette recorders yielded lower and upper cut-off frequencies of 0.06 and 0.07, and 20 and 16 Hz, respectively. A phase shift of -30 degrees was found at 0.35 and 0.31 Hz, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2922954 TI - Determination of methadone in human hair by radioimmunoassay. AB - The concentrations of methadone in human hair were measured. The washed hair was cut in 1-mm pieces approximately, then incubated overnight at 45 degrees C with 0.1 m HCl. The extracts were alcalized by 1 m NaOH and diluted by phosphate buffer, pH 7.4. The methadone concentrations were determined by radioimmunoassay. The method is simple, rapid, and practicable for routine determination. PMID- 2922955 TI - [Forensic medicine and morphologic aspects of fatal amniotic fluid aspiration]. AB - The massive aspiration of amniotic fluid as one cause of a fatal postpartal asphyxia will be demonstrated under the aspect of preliminary criminal law proceedings against physicians because of medical negligence. The pathomorphologically established diagnosis of a fatal aspiration of amniotic fluid supposes extensive and systematic quantitative histological examination of both lungs. The technique of histological cross sections through the entire lung combined with morphometry is a suitable method to exactly record the alterations of bronchi and lung parenchyma by aspiration of amniotic fluid and their complications, such as interstitial emphysema. PMID- 2922956 TI - [Comparative histologic studies of the origin of petechial thymus hemorrhage]. AB - Systematic histological investigations were carried out on the thymus with regard to the incidence and genesis of petechial thymus hemorrhages in 145 cases of death (fetuses from pregnancy terminations and stillbirth, mature and immature neonates, SIDS cases, other baby deaths, deaths during infancy and childhood). Petechial thymus hemorrhages were most frequently found in SIDS cases (87%). Even though distinguishable, a distribution pattern similar to that of thymus hemorrhages in SIDS cases (including hemorrhages mainly in the cortical zone of the lobes) could be detected in the group of fetuses from pregnancy terminations and stillbirth, as well as in mature and immature neonates. Histologically, deaths in babies and infants without extrinsic suffocation showed a different histological bleeding pattern (irregular hemorrhages of varying size in the cortex and medulla of the lobes). In violent extrinsic suffocation of babies and infants, thymus hemorrhages were much rarer and less pronounced in quantitative terms. Acute and subacute or chronic forms of asphyxia, the cause of death and the duration of the death struggle are discussed as pathogenetic factors to explain the different patterns of the findings. PMID- 2922957 TI - [Gunshot wounds of the head in soldiers wearing military helmets-- general aspects and experiments and observations on the biomechanics and wound morphology]. AB - With respect to wound ballistics, the situation is different if the person wearing a military helmet suffers head injuries from a bullet. The mechanisms of injury were investigated in four experimental series and supplemented by a case history. The study showed surprising results: in the majority of cases, the helmet does not protect the wearer, but instead intensifies the damage caused by the bullet. The reasons for this phenomena are changes in the stability of the projectile and deformation of or damage to the bullet. All of these mechanisms result in the bullet striking the tissue with higher energy. In this investigation, Kevlar helmets were also tested, which are not penetrated by 9 X 19 mm parabellum bullets. Even so, however, severe injuries of the skull and brain can occur because the projectile causes intensified impressions on the skull under the helmet and, in addition, an acceleration of the head. PMID- 2922958 TI - Genetic polymorphisms of orosomucoid ORM1 and ORM2 in a Japanese population: occurrence of new ORM1 alleles. AB - Genetic polymorphisms of orosomucoid ORM1 and ORM2 in a Japanese population from northern Japan were investigated using isoelectric focusing (IEF) in ultrathin layer polyacrylamide gels containing Triton X-100 and immunofixation. Nine ORM1 phenotypes which are determined by four common and one rare alleles were observed. Two of the identified alleles at this locus were considered to be new. The ORM2 pattern was classified into 14 phenotypes as products of one common and two variant alleles. The estimated allele frequencies were ORM1*1 = 0.668, ORM1*2 = 0.170, ORM1*2.1 = 0.136, ORM1*5.2 = 0.022 and ORM1*7 = 0.004; ORM2*1 = 0.972, ORM2*3 = 0.006 and ORM2*6 = 0.022. PMID- 2922959 TI - A case of Churg-Strauss syndrome. AB - A 54-year-old woman died after being battered, but the forensic autopsy revealed that her injuries were not serious or lethal. A detailed histological examination revealed that the basic disease had been Churg-Strauss syndrome. The differentiation of this syndrome of pulmonary infiltration and eosinophilia (PIE syndrome) from other allergic and noninfectious granulomatoses needs cautions consideration. PMID- 2922960 TI - [Forensic medicine and toxicologic aspects of 2-propanol poisoning]. AB - Two cases of poisoning with 2-propanol (isopropylalcohol) are reported. In one case, nail polish remover was drunk by a 2-year-old child. The concentration of 2 propanol and its metabolite acetone in the blood could be observed over a period of approximately 50 h. The highest concentration of 2-propanol determined was 4.22 g/l. Acetone reached a maximum value of 2.27 g/l 12 h after ingestion. The child survived without any observable after-effects. In the second case, a 35 year-old man drank ethanol in addition to 2-propanol. The poisoning was lethal. The possible time of intake before death is discussed in relation to the estimated levels of ethanol, 2-propanol and acetone found in the blood and urine. The histomorphological findings are often important as well with regard to time of intake. PMID- 2922961 TI - [Follow-up study of affect, anxiety and aggression in inpatient treatment of anorexia nervosa]. AB - Under the assumption of affect-defense (alexithymia) n = 20 anorexia nervosa patients being treated in the University Hospital of Hamburg-Eppendorf from 1980 to 1982 were examined with respect to their affects of anxiety and aggressivity by employing speach samples (three times a week)--according to Gottschalk-Gleser- and questionnaires (ANIS) during hospitalization and compared to n = 10 control patients from somatic clinics (orthopedics, surgery, gynecology). Particularly examined were emotional responses toward events during the in-patient period. As the most important result we found distinct affectivity in the anorexia patients that was partly stronger than that of the somatic control patients, so that (judged from our sample of anorexia nervosa) the hypothesis of alexithymia has to be rejected. PMID- 2922962 TI - [Decoupling or ultra-short therapy of torticollis]. AB - S. Rentrop's survey of literature on the history of the psychotherapeutic treatment of torticollis (76 titles) last year has encouraged us to contribute two examples of treatment to the discussion. The large number of theories, explanations, and treatment methods reveals the wide variety of increasingly effective treatment techniques, but it also makes apparent the dilemma involved in the search for a clear and comprehensive theory. On the basis of two case studies, we would like to show how torticollis symptoms could be eliminated with the help of a one-time focus on a largely unconscious traumatic complex, without additional therapy. One of the two female patients was treated in a supportive clinical environment, the other appeared at the out-patient clinic only once. Finally, we discuss the theoretical approach involved. PMID- 2922963 TI - [Changes in regional cortical blood flow in hypnosis]. AB - Regional cerebral blood flow (rCBF) was measured by means of the 133-Xenon inhalation method in 12 healthy male volunteers experienced in self-hypnosis for several months. During a well performed levitation of the right arm in hypnosis as compared to resting conditions, we found a global increase of cortical blood flow and a regional activation of temporal areas; the latter finding is considered to reflect acoustical attention. In addition, a so far unexplained desactivation of inferior temporal areas was observed during successful self hypnosis and hypnosis. While there was a global absolute increase of cortical blood flow bilaterally, we could not observe a relative increase of the right as compared to the left hemisphere during hypnosis. Several subjects successfully performed the levitation of the right arm, despite a relative left hemispheric activation, provided the absolute right hemispheric activation remained dominant. PMID- 2922964 TI - [The impact of perceptual stereotypes in indications for psychoanalysis]. AB - Results of several experimental studies concerning the practice of selecting patients for psychoanalytic therapies are presented. The convergent findings strongly suggest that the indication for psychoanalytic therapies are heavily stereotyped and are dependent upon stimuli that do not result from communicative interaction with the patient. These facts are confronted with the psychoanalytic understanding of the role of countertransference during the indication process. Countertransference and stereotypes person perception do not necessarily contradict each other. It is proposed that countertransference reactions in this situation are partly a consequence of compatibility stereotypes vis a vis the patient which are quickly and unconsciously formed and which are afterwards differentiated and extended but also rationalized on a conscious level. PMID- 2922965 TI - [Differentiation of the long-term effects of inpatient psychosomatic therapy of patients with anorexia nervosa]. AB - In a catamnestic study of 103 anorexia nervosa patients treated at the university medical clinic in Heidelberg between 1970 and 1980, 51 patients were personally evaluated after 3, 6 years using a multi-dimensional system of criteria that covered 30 different symptom areas. There was a clear improvement with regard to constipation, vomiting, and the abuse of laxatives, various laboratory parameters, psychic symptoms, and vocational situation. Secondary amenorrhea, psychic suffering, and overly strong emotional ties to the family, however, were still found among two-thirds of the patients. Long-term success of treatment was found to correlate closely with an early age both for the onset of the disorder and for the beginning of treatment. Reduction of physical symptoms by the time of the post-examination was closely related to the extent of the family therapy carries out. In general, males appeared to benefit from treatment more than did female patients. Cluster analysis revealed that of four groups of patients studied, only one group could be called healthy; anorexia nervosa symptoms persisted to varying degrees in the other groups. Psychological testing using the PEF brought to light the following relationships: The greater the degree of illness at the time of the catamnestic study, the stronger the patient's tie to his/her own family, the greater the concern with physical appearance, the more achievement oriented, and the greater the aversion to playful activity. PMID- 2922966 TI - [Hemodynamic characteristics of necrotizing pancreatitis]. AB - Seventy-one patients with necrotizing pancreatitis in stages II and III were treated at the surgical intensive care unit in the authors' hospital, between 1982 and 1986. Pathological courses in 23 patients were so severe that a pulmonary catheter had to be applied to monitor haemodynamic changes. Seventeen of these 23 patients died (73.9 per cent), while six survived. The gravest difference between these two groups was relating to vasculopulmonary resistance, which went up strongly in the first group (428 +/- 19 dyn X sec X cm-5) and stayed moderate in the second (201 +/- 13 dyn X sec X cm-5). The left-ventricular stroke work index in the first group was lower with significance than that in the second, the values being 33.4 +/- 2 g X m/m2 versus 44 +/- 4.6 g X m/m2. PMID- 2922967 TI - The anergic state as a predictor of pancreatic sepsis. AB - From 1984 to 1987, 187 patients with acute pancreatitis (AP) were studied. All patients were stratified according to Ranson's criteria upon admission and were followed up by performing a CT scan weekly. One hundred and thirty-eight patients had 3 or less Ranson's criteria (non-severe acute pancreatitis = NSAP) and 49 presented 4 or more (severe acute pancreatitis = SAP). Ninety-six percent of the patients with (p less than 0.0001). Of the 49 patients with SAP, 39 developed pancreatic or peripancreatic NSAP were reactive to skin tests on the third week, while 4% remained anergic necrosis and were operated. Twenty-two of these patients had positive cultures demonstrating the presence of bacteria in the tissue samples. One hundred percent of the infected patients remained anergic until surgery, while only 40% of those with negative cultures remained anergic (p less than 0.05). Mortality rate correlated well with skin test responses, being 31% in anergic patients while only 5% in reactive subjects. Sustained anergic state (AS), sequentially checked, is associated with a high incidence of pancreatic sepsis. PMID- 2922968 TI - [Results of surgical treatment of chronic pancreatitis]. AB - On the basis of a group of 67 patients studied by the authors, the various techniques for the surgical treatment of chronic pancreatitis are discussed. The average age of the patients covered by this study was 45.7 years, and the male:female ratio was 2.9:1. In more than 82% of the cases a history of chronic alcohol abuse was definitely established. For the drainage operations performed the preferred operative techniques were the pancreaticojejunal anastomosis and, where pancreatic pseudocysts were present, the cystojejunostomy. Resection of the pancreas was performed in a total of 18 patients, the clinical mortality here being 5.6%. In our study also the long-term prognosis for patients with chronic pancreatitis depended, on the whole, less upon the operative technique chosen than upon the subsequent degree of alcoholism. PMID- 2922969 TI - [Pancreatic kinetics of ampicillin]. AB - Intravenous application of 50 mg/kg of ampicillin was followed by determination of ampicillin concentrations in surgically removed pancrease tissue of human patients and dogs. Concentration curves in pure pancreatic juice were recorded from dogs in which external pancreatic fistulae had been surgically induced. The ampicillin concentrations recorded from both human tissue and dogs were as low as six to eight per cent relative to corresponding serum levels. Values as low as 0.13 to 1.5 per cent relative to corresponding serum levels were recorded from pure pancreatic juice of dogs and from one human patient. These findings are likely to suggest that the permeation of ampicillin into the pancreas i too low and, consequently, cannot be effective for prophylaxis and therapy in the context of infectious complications. PMID- 2922970 TI - [Data on surgical indications in necrotizing pancreatitis--results of a validation study]. AB - 134 patients with necrotizing pancreatitis were operated. Preoperative organ insufficiency (pulmonary or renal), the presence of shock or sepsis and the intraoperative morbidity factors: parenchymal necroses greater than 30%, extrapancreatic necroses, ascites and in particular bacterial contamination were directly correlated with prognosis and mortality. The occurrence of these morbidity factors consequently signifies an urgent indication for operation. PMID- 2922971 TI - Intraperitonealisation of pancreas and multiple coeliostomy--a possible approach to reduce mortality of acute necrotizing pancreatitis. AB - The authors report their experience with surgical treatment of acute necrotizing pancreatitis. 207 of 411 patients with acute pancreatitis were operated upon. Acute necrotizing pancreatitis was found in 126 individuals. The following surgical procedures were used: subtotal spleno-pancreatectomy in 26 cases (20.6 per cent), necrectomy or sequestrectomy in 25 cases (19.7 per cent), and conservative procedures, including drainage or incision of the pancreatic capsule, in 76 cases (70.6 per cent). Most of the operations were delayed emergency interventions. The authors found adequate exposure of the pancreas as well as on proper drainage of the lesser sac and retroperitoneal areas essential. This can be accomplished by means of the authors' procedure called "intraperitonealisation" of the pancreas and by multiple coeliostomy. PMID- 2922973 TI - [The role of peritoneal lavage in the surgical treatment of acute necrotizing pancreatitis]. AB - Treatment of patients for acute pancreatitis is reported in this paper, with particular reference being made to the effectiveness of peritoneal lavage. Aetiological factors as well as surgical indications and techniques are communicated against the background of ten years of experience. Results are separately reported for two periods under review, with no peritoneal lavage used in the first phase. Results improved, and lethality rates dropped in the second five-year period, despite growing numbers of severe courses. Effects of peritoneal lavage are considered possible in the latter cases. However, mortality in the wake of early surgery has continued to be high, that is in connection with most severe forms of pancreatitis (when surgical action had been taken in the first week of manifest illness). No improvement appeared to be obtainable in such cases from postoperative peritoneal lavage. PMID- 2922974 TI - [Follow-up of node-negative patients with breast cancer]. AB - In 136 cases of nodal-negative breast cancer, the further course regarding the incidence of metastases or recurrence was observe over a period of up to 83 months. Parameters have been tumor size, location, grading, the number of extirpated lymphatic nodules, hormone receptor status, and menopause status. After a mean observation period of 3.5 years, distant metastases had appeared in 23 cases = 16.9%. In this collective, the recurrence rate in premenopausal patients was 17.4% in postmenopausal patients ones 16.7%. An interesting trend became apparent in correlation between relapse and conducted primary therapy: All patients with tumor stage T1 who had received chemotherapy - at least one cycle of CMF - were free of relapse partially over the complete observation period. Regarding the fact that early hematogenous dissemination is also possible without involvement of regional lymphatic nodules, at least a perioperative chemotherapy appears useful. Definite statements concerning usefulness and efficiency of this mode of therapy however are only possible after evaluation of results of controlled studies. PMID- 2922972 TI - [Intensive therapy of acute necrotizing pancreatitis]. AB - The prognosis of pancreatitis can be improved by persistent involvement of intensive therapy in the therapeutic concept applied to acute cases. Abdominal lavage, properly timed relaparotomy, analgesia through peridural catheter, artificial ventilation in cases of respiratory insufficiency, and adequate fluid substitution are some of the measures by which the course of acute pancreatitis can be most effectively tackled. Results so far obtained from this therapeutic concept are reported in some detail. PMID- 2922975 TI - [Detection and significance of tissue polypeptide antigen (TPA) in breast cancer patients]. AB - 20 female with breast cancer aged between 44 and 72 years have been investigated for tissue-polypeptid-antigen (TPA). 20 females without any disorders of the breast were included in our control group. Their age ranged between 22 and 48 years. Patients with breast cancer have been treated by limited-radical mastectomy according to Auchincloss-Madden followed by axilla dissection and chemotherapy. Cancer has been typed pathohistologically, graded and classified using TNM-nomenclature of maligne tumours. So we can characterize our patients as "pT2N1M0". We estimated TPA preoperativ upto 24 months postoperatively. Our results showed an early and significant increase of TPA in 5 patients suffering a recurrence. PMID- 2922976 TI - [Partnership status in preparation for therapeutic donor insemination]. AB - An investigation is presented which inquiries the psychological problems of sterile couples after diagnosing of male infertility. The interpretation of conversation topics accomplished by 460 couples suggests that coping with infertility by the couple, the character of the desire for a child, the level of stress tolerance, the ability to cooperation and the agreement to compromise determine the psychological situation of a couple infertile by male. These facts should be taken into consideration in regard of the therapeutic insemination by donor. PMID- 2922977 TI - [Diagnosis of thyroid function in uterine myomatosis]. AB - A correlation between thyroid disease and uterine myoma has been discussed till the fourth decade of this century. Since then, this possible connection was given no further notice. We examined 79 women needing a hysterectomy for various reasons regarding myometrial histology, thyroid function and thyroid antibodies. The patient group bearing myomas showed significantly more frequent (23%) pathological TRH/TSH stimulation tests results than the control group (3.7%, p = 0.0543). 10 of 22 patients with myomas had microsomal and/or thyroglobin antibodies, compared with none in the control group (n = 17, p = 0.0019). Therefore regarding these results a connection between thyroid disease and uterine myoma should undergo a more detailed examination. PMID- 2922978 TI - [Attitude and sex behavior following hysterectomy]. AB - 488 women have been asked after abdominal or vaginal hysterectomy by way of retrospective questionnaires about preoperative anxieties, postoperative psychosomatic complaints as well as disturbances of their vita sexualis. 48.6% of the patients had anxieties before operation and anaesthesia. After hysterectomy 71.9% of the women reported about hot flushes and other psycho-vegetative complaints. Although hot flushes occurred significantly more frequent in patients with salpingooophorectomy they could be observed also in one third of the women without removal of the ovaries. However libido, cohabitation frequency and orgasm ability were reduced significantly more frequent in the group of women after hysterectomy with salpingooophorectomy. This is caused by the failing blood supply to the ovary via the branches of the uterine artery. The reduce postoperative psychosomatic complaints as well as sexual dysfunctions it is important to give qualited instructions before and after the operation. On no account should a prophylactic exstirpation of the adnexa be carried out before the age of 50 years. A hormonal substitution is recommended to be done in time even for patients whose ovaries have not been removed suffering from psycho somatio discomforts. PMID- 2922979 TI - [Hematohydrometra 11 years after cervix conization: a cause of acute massive lung thromboembolism]. AB - In this case report an unusual chain of late complications with a fatal outcome following conization is presented. A scarred obliteration of the cervix resulted in the development of a hematohydrometra, which caused a calf vein thrombosis by compression of the vena iliaca externa with obstruction of venous outflow of crural vessels and a final massive pulmonary thrombo-embolism 11 years after the surgical procedure. PMID- 2922980 TI - Continuous infusion of midazolam during anaesthesia and postoperative sedation after maxillofacial surgery. AB - The clinical effects and pharmacokinetics of 24 h infusion of midazolam (MDZ) during major maxillofacial surgery and postoperative observation in an Intensive Care Unit (ICU) were studied in 20 patients. During anaesthesia, infusion of MDZ at 5 mg/h combined with 67% nitrous oxide, 1.8 (s.d. = 0.8) mg of fentanyl, and 26.5 (s.d. = 11.4) mg of vecuronium, adequately suppressed clinical responses to surgical nociceptive stimuli. Postoperatively, infusion of MDZ was continued in the ICU at 5 mg/h until 9 a.m. of the first postoperative day for sedation of the intubated but spontaneously breathing patients. The depth of sedation in the ICU was scored from 1-5 (1 = "awake and tense", 5 = "unable to communicate"). During infusion the sedation score decreased from 3.8 after ICU arrival to 2.2 at 8 a.m. of the first postoperative day. Neither ventilatory nor circulatory depression were observed. After cessation of MDZ, recovery from sedation was fast. The degree of amnesia was low. During constant rate infusion no increase in plasma concentration of either MDZ or metabolites occurred. T1/2 beta of MDZ after cessation was 125 min (range 90-320) and its total body clearance was 10.5 ml/kg/min (s.d. = 3.1). The volume of distribution, clearance and T1/2 beta were significantly longer in women than in men. It was concluded that 24 h of MDZ infusion at 5 mg/h caused satisfactory ICU sedation with fast recovery, but that individual tailoring of the infusion rate may still improve the quality of sedation. PMID- 2922981 TI - Suppression of neutrophil migration and chemiluminescence is due to the sulphur atom in the thiobarbiturate molecule. AB - In this study the hypothesis was tested that the substituent at the C 2 position of the barbiturate molecule is crucial for the obvious differences in inhibitory potencies between various barbiturates with respect to neutrophil functions in vitro. Using isolated neutrophils from healthy volunteers, the comparative effects of two pairs of sulphur or oxygen-substituted analogues on chemiluminescence, random and chemotactic migration were examined. Five other i.v. barbiturates were also tested in the chemiluminescence assay. The key observation with all the assay systems was that the oxybarbiturates proved ten to a hundredfold less suppressive than their sulphurated analogues or the other thiobarbiturates. Thus, enhanced inhibitory potency was dependent on the presence of the sulphur atom in the barbiturate molecule and could no longer be explained exclusively on the basis of divergent physicochemical features. PMID- 2922982 TI - Thoracic paravertebral block: a method of pain control. AB - The adverse effects of pain on acutely ill or traumatized patients are well documented. A variety of pain-relieving techniques are now available to meet the varied requirements for pain relief. This paper presents the results of a single, large-volume injection of bupivacaine 0.5% in the thoracic paravertebral space, achieving pain relief over several thoracic dermatomes in patients with respiratory compromise secondary to thoracic or upper abdominal injury. The block proved quick and simple to perform, with excellent clinical results of long duration and virtually no complications. Although not previously described, this single, large-volume injection approach to achieving an extensive thoracic paravertebral block may well become an important pain management technique in appropriate patients. PMID- 2922983 TI - Early detection of the TUR syndrome by marking the irrigating fluid with 1% ethanol. AB - The ethanol concentration in the expired breath (EB-ethanol), the volumetric fluid balance and the serum sodium concentration were measured in the course of 60 transurethral resections of the prostate in which the irrigating fluid was 1.5% glycine + 1% ethanol. Measurement of EB-ethanol indicated absorption of irrigant at a rate of more than 150 ml in 10 min, as measured volumetrically. There was a significant direct linear relationship between EB-ethanol and the cumulative volume of irrigant absorbed (R2 = 0.83); this correlation was stronger when the duration of absorption was taken into account (R2 = 0.90). EB-ethanol was inversely related to the overall change in the serum sodium concentration during the operation (R2 = 0.88). Symptoms that are recognized components of the TUR syndrome developed in 8 of the 13 patients absorbing more than 11 of irrigant, while the ethanol exerted no adverse effects. The results of the study indicate that 1% ethanol is a suitable marker for monitoring irrigant absorption by means of the expired breath test in routine transurethral surgery. At this concentration the sensitivity of the test is adequate for detecting absorption, while the ethanol is less toxic than the irrigant fluid itself. PMID- 2922984 TI - Epidural morphine delays gastric emptying and small intestinal transit in volunteers. AB - The influence of a painful stimulus and lumbar epidural morphine on gastric emptying, the orocecal transit time and small intestinal transit were studied in nine healthy volunteers. Acetaminophen absorption was used as a measure of the rate of gastric emptying. Orocecal transit time was determined by measuring the end-expiratory hydrogen concentration. Small intestinal transit was calculated from measurements of the orocecal transit time and gastric emptying. Cold pain stress with intermittent immersion of the feet in ice-cold water was used as a painful stimulus. Each volunteer was investigated on 3 different days: once after receiving 4 mg of epidural morphine and during cold pain; once during cold pain; and once under control conditions without pain and epidural morphine. Immersion of the feet in ice-cold water was always very painful, but was more tolerable during epidural morphine analgesia. The increase in blood pressure which accompanied the cold pain was the same whether this pain was induced without or during epidural morphine analgesia. Gastric emptying, orocecal transit time and small intestinal transit were delayed during epidural morphine analgesia compared with the findings under the control and plain cold pain conditions. Cold pain stress alone did not influence gastric emptying, orocecal transit time or intestinal transit. To conclude, epidural morphine in itself delayed gastric emptying, orocecal transit and transit through the small intestine in healthy volunteers. PMID- 2922985 TI - Effects of epidural bupivacaine and epidural morphine on bowel function and pain after hysterectomy. AB - A comparison was made of the effects of continuous epidural analgesia with bupivacaine and intermittent epidural morphine on bowel function after abdominal hysterectomy. The duration of postoperative ileus was assessed as the time from the end of operation to the first postoperative passage of flatus and feces. Twenty-two patients were randomly allocated to two equal groups. An "epidural morphine" group received general anesthesia and epidural morphine for postoperative pain relief, and an "epidural bupivacaine" group was given combined general anesthesia and epidural anesthesia with 0.5% bupivacaine intraoperatively and epidural analgesia with 0.25% bupivacaine postoperatively. Epidural morphine or bupivacaine was given for 42 h postoperatively. Pain intensity (visual analog scale) was low in both groups, but lower (P less than 0.05) in the epidural bupivacaine group. The time to first passage of flatus was 22 +/- 16 h in the epidural bupivacaine group and 56 +/- 22 h in the epidural morphine group (P less than 0.001). The time to first postoperative passage of feces was shorter (P less than 0.05) in the former than in the latter 57 +/- 44 h vs 92 +/- 22 h). The patients of the epidural bupivacaine group started intake of oral fluids earlier (P less than 0.01) and to a greater extent (P less than 0.05) than those in the epidural morphine group. It is concluded that the duration of postoperative ileus after hysterectomy is shorter when epidural bupivacaine is given for postoperative pain relief than when this is achieved by epidural morphine. PMID- 2922986 TI - Cardiotoxicity of ropivacaine--a new amide local anaesthetic agent. AB - Anaesthetically equipotent doses of lidocaine, bupivacaine and a new bupivacaine like local anaesthetic agent, ropivacaine, were injected into the left anterior descending coronary artery of pentobarbital-anaesthetized pigs. The aim was to study the cardiotoxicity of ropivacaine in relation to the two other drugs. A random, crossover, dose response study design was used. The following doses of the drugs were administered: lidocaine (L): 1,2,4,8 and 16 mg, bupivacaine (B): 0.25, 0.5, 1,2 and 4 mg and ropivacaine (R): 0.33, 0.66 1.33, 2.66 and 5.33 mg. Systemic haemodynamics, left ventricular dP/dT and a 12-lead electrocardiogram were recorded continuously during the study period. The drugs depressed cardiac contractility in relation to their local anaesthetic potency on the isolated nerve-4:3:1 (B:R:L). The prolongation of the ECG QRS-interval was regarded as a measure of electrophysiologic toxicity. Comparable prolongation of the QRS interval was recorded after 2 mg of bupivacaine, 4.5 mg of ropivacaine and 30 mg of lidocaine. Thus, the electrophysiological toxicity ratio was 15:6.7:1 (B:R:L). Provided local anaesthetic potency data can be extrapolated from the isolated nerve preparation to regional anaesthesia in humans, ropivacaine appears to provide a greater margin of safety than bupivacaine, if inadvertently injected into the venous circulation. PMID- 2922987 TI - The risk of ischaemic brain damage during the use of self-retaining brain retractors. AB - Self-retaining brain retractors (SRBR) are commonly used during intracranial surgery and they are indispensable during microneurosurgery. To evaluate limitations in the employment of SRBR, as well animal as human studies have been performed. In the animal studies, male Wistar rats were used for measurements of regional cerebral blood flow (rCBF) changes during brain retractor pressure (BRP) provided by lead weights. These weights, corresponding to different levels of mm Hg, were applicated for different periods of time on the parietal cortex after craniotomy. In one part of the animal studies different profiles of the application surface of the weights were evaluated. For measurement of the rCBF (n = 41) autoradiography with carbon-14(14C)iodoantipyrine was used as described by Gjedde et al (1980). A neuropathological method (n = 30) was used to reveal possible brain damage after graded BRP. In the rats the thresholds of rCBF, regional cerebral perfusion pressure (rCPP) and time were 20-25 ml/100 g/min, 20 mm Hg and 7-10 minutes respectively. In the human studies only alert patients without neurological deficits (except defects of the visual fields) and in whom preoperative CT-scans did not disclose any sign of infarction were included. BRP beneath as well the tip as the centre of the SRBR and the MABP were recorded continuously. Patients with peroperative complications were excluded. During the operations induced hypotension (n = 20) and mannitol (n = 6) were administrated. The patients (n = 23) had a 3-month follow-up examination. In man the thresholds of rCPP and time were found to be 10 mm Hg and 6-8 minutes, respectively. Other authors have found a rCBF threshold of 10-13 ml/100 g/min (Astrup 1982, Iannotti & Hoff 1983). It is concluded that the results obtained in the rat studies are comparable to the human situation if reservations are made concerning the differences in the thresholds of rCBF and rCPP. The time threshold of cerebral ischaemia seems to be rather equal in rat and in man. If these thresholds are reached, intermittent BRP is absolutely recommendable. It was also found that the most easily-handled retractors, those with a flat profile, did not decrease the rCBF further than other types of retractors. PMID- 2922988 TI - Neuroendocrine markers in central nervous system neuronal tumors (gangliocytoma and ganglioglioma). AB - We studied five cases of central nervous system neuronal tumor, one gangliocytoma and four gangliogliomas, both ultrastructurally and immunohistochemically, using antibodies to neuroendocrine markers including tyrosine hydroxylase (TH), serotonin (5HT), somatostatin (SOM), met-enkephalin (MEK), leu-enkephalin (LEK), substance P (SP), gastrin, vasopressin, oxytocin, vasoactive intestinal polypeptide, adrenocorticotropic hormone and calcitonin. In all cases, the presence of dense-core vesicles (60-250 nm) in the neuronal elements was the characteristic ultrastructural finding. Synapses were observed in two cases. Immunohistochemically, variable numbers of neuronal cells showed positive staining for SOM in five cases, TH, MEK and LEK in three cases, and 5HT and SP in one case each. The others were negative. Positive immunoreactivity for multiple markers was shown in all cases. SOM, TH, 5HT and SP were present in the small- to medium-sized cells, while MEK and LEK were almost exclusively confined to the large cells. Our study clearly indicated that these tumors contained neuronal cells which were not homogeneous with regard to neuroendocrine markers. PMID- 2922990 TI - In situ analysis of cell kinetics in human brain tumors. A comparative immunocytochemical study of S phase cells by a new in vitro bromodeoxyuridine labeling technique, and of proliferating pool cells by monoclonal antibody Ki-67. AB - A newly developed in vitro labeling method with bromodeoxyuridine (BrdU) identifies S phase cells in situ in freshly obtained surgical tissue of human brain tumors which is subsequently fixed and embedded in paraffin for BrdU immunovisualization. For the first time, the BrdU labeling index (LI) is successfully compared here with the LI obtained by immunostaining of frozen sections of the same tumors with monoclonal antibody Ki-67 which identifies all proliferating cells, i.e., the growth fraction. LIs were counted in at least five different areas with high density of labeled cells; at least 1,000 cells were counted. In 13 metastatic tumors, Ki-67 LI was 8.3%-62.6%, and BrdU LI was 5.1% 28.0%. In 18 gliomas, Ki-67 LI was 1.4%-19.3%, and BrdU LI was 0.2%-11.6%. In 7 meningiomas, Ki-67 LI was 0.3%-3.0%, and BrdU LI was 0%-2.0%. Statistical comparison of Ki-67 and BrdU LIs by linear regression analysis revealed a highly significant correlation: BrdU LI = 0.99 + 0.34 Ki-67 LI (r = 0.92, P less than 0.001). A significant heterogeneity of proliferation patterns may occur within one sample from area to area, as well as between different samples of the same tumor, especially in gliomas; thus, some subjective influence on LIs by arbitrary sampling and selection could occur in quantitative evaluation of in situ cell kinetics of human brain tumors. This study indicates that our in vitro BrdU labeling method allows the in situ identification of S phase cells in excellently preserved fixed tumor tissue which is well suited for further histological examination.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2922989 TI - Further confirmation of serotonin reduction in the neostriatum during hyperthermia-induced convulsions: a quantitative immunohistochemical study. AB - Changes occurring in serotonin neurons during hyperthermia and hyperthermia induced convulsions were examined by quantitative immunohistochemistry. A marked increase in serotonin immunoreactivity was observed at the rostral and intermediate levels of the neostriatum of mice kept at high temperatures with no convulsions, and a significant reduction in serotonin immunoreactivity was verified throughout the neostriatum of mice which had hyperthermia-induced seizures. These results suggest that serotonin neurons change significantly during thermal stress and seizures, and that regional analysis is essential for an understanding of the role of serotonin neurons. PMID- 2922991 TI - Ganglioside mapping of a human medulloblastoma xenograft. AB - The ganglioside patterns of medulloblastomas have never been established; in this study we report the ganglioside profile of the human medulloblastoma cell line TE 671 grown as a xenograft in nude mice. Gangliosides were isolated and structurally analyzed by fast atom bombardment mass spectometry following permethylation. Identification of individual gangliosides was also performed by immunostaining of high-performance thin-layer chromatography-separated bands. Total ganglioside levels of 0.20 mumol/g of tissue were obtained, consistent with those reported for human glioma cell lines grown as xenografts; predominant monosialogangliosides of TE-671 xenografts were II3-alpha-NeuAc-LacCer (GM3) and II3-alpha-NeuAc-GgOse3Cer (GM2) but there were also relatively large proportions of IV3-alpha-NeuAc-LcOse4Cer (3'-isoLM1), IV3-alpha-NeuAc-nLcOse4Cer (3'-LM1) and a further ganglioside of the neolacto-series with an extra lactosamine moiety. The only oligosialoganglioside detected was IV3, II3-alpha-NeuAc2-GgOse4Cer (GD1a). PMID- 2922992 TI - Cerebellar injury due to phenytoin. Identification and evolution of Purkinje cell axonal swellings in deep cerebellar nuclei of mice. AB - The present study describes the identification and the ultrastructural and numerical evolution of Purkinje cell axonal swellings induced by phenytoin. Thirty male C57Bl/6J mice received phenytoin orally in doses up to 100 mg/kg daily and were killed after 3, 6, 10, 14, and 48 days of treatment. Light and electron microscopic investigations as well as morphometric analysis of cut surface area and numerical density of axonal swellings were performed. The swellings appeared as early as 6 days after initiation of treatment and gradually increased in size and frequency. Use of an anti-lymphocyte monoclonal antibody (CD 3), specifically cross-reacting with Purkinje cells, identified the swellings as dystrophic Purkinje cell axons. On grounds of their ultrastructural appearance they were classified into three distinct types occurring at different time intervals after phenytoin exposure. At 6 days, most axonal swellings contained loosely aggregated membranous vesicles and tubules in a finely granulated matrix (type 1). At 14 days, larger axonal swellings appeared characterized by the presence of three-dimensional networks of branched and anastomosing membranous tubules (type 2). At 48 days, even larger axons contained bodies of highly condensed membranous material of sometimes paracrystalline appearance (type 3). It is suggested that phenytoin-induced axonal pathology of Purkinje cells is a dynamic process characterized by the progressive accumulation of proliferating membranous material arranged in an increasingly complex fashion. PMID- 2922993 TI - Complement-derived polypeptide C3adesArg as a mediator of inflammation at the blood-brain barrier in a new experimental cat model. AB - The effect of the complement-derived polypeptide C3adesArg as a mediator of inflammation in the central nervous system was examined. Twenty-five anesthetized cats received 4 mg of this polypeptide by intraventricular injection, 20 cats who served as controls received saline. Cerebrospinal fluid (CSF) was sampled 3 h after intraventricular injection and the brains were removed. For assessment of the permeability of the blood-brain barrier the CSF penetration of four antibiotics, which were given intravenously was measured. Five control animals were employed for each antibiotic (tobramycin, ampicillin, imipenem, fosfomycin), whereas six C3adesArg-treated animals were used for each antibiotic and seven for tobramycin. Besides CSF levels of glucose, the prostanoids 6-keto-prostaglandin F1 alpha, thromboxane B2 and prostaglandin E2 were measured. The morphological examinations in the CSF sediments and histological brain sections in the C3adesArg-treated animals disclosed a distinct inflammation with leptomeningeal and perivascular infiltration of polymorphonuclear granulocytes compared to normal findings in the controls. The CSF/serum ratios of all of the antibiotics were markedly elevated compared to controls, indicating a blood-brain barrier disruption. The levels of all prostanoids were significantly higher in the treatment group than in the control group, whereas the glucose levels were lower. These findings are in accordance with a granulocytic meningitis as seen in some infections at the acute stage. It is concluded that C3adesArg acts as a mediator of inflammation in the central nervous system. PMID- 2922995 TI - An autopsy case of familial juvenile Alzheimer's disease with extensive involvement of the subcortical gray and white matters. AB - An autopsy case of familial juvenile Alzheimer's disease with extensive involvement of the subcortical gray and white matters is reported. A 33-year-old woman showed a progressive dementia and died of cardiac failure at the age of 45. Neurological examination disclosed choreatic movements, myoclonus, rigidity, and generalized convulsion. Gross inspection of the brain showed a diffuse cerebral atrophy and marked degenerations of both the subcortical gray and white matters. Microscopically, numerous and extensive argyrophilic changes such as senile plaques, neurofibrillary tangles, and granulovacuolar degenerations were observed in the brain. The present case was characterized by a severe neuronal loss in the basal ganglia, substantia nigra, dentate nucleus, and thalamus as well as a marked myelin loss and axonal damage in the cerebral white matter. This case suggested a combination of multisystemic degeneration and primary degeneration of the cerebral white matter. The pathological similarity of this case to Creutzfeldt-Jakob disease and Pick's disease is discussed. PMID- 2922994 TI - Immunocytochemistry of four mixed pituitary adenomas and intrasellar gangliocytomas associated with different clinical syndromes: acromegaly, amenorrhea-galactorrhea, Cushing's disease and isolated tumoral syndrome. AB - Four tumors consisting of pituitary adenomatous cells (AD) intricated with ganglion cells (GC) were studied. Each case was associated with a different clinical syndrome: acromegaly, amenorrhea-galactorrhea, Cushing's disease and isolated tumoral syndrome with no hormonal hypersecretion. (a) In the case with acromegaly, immunoreactive growth hormone (IR-GH) was present in 80% of AD. IR vasoactive intestinal peptide (VIP) was found in 5%-10% of AD and in few GC. Rare GC and processes showed IR-GH-releasing hormone (GRH), -somatostatin (SRIH), gonadotropin-releasing hormone and -adrenocorticotropin-releasing hormone. (b) In the case with amenorrhea-galactorrhea, IR-prolactin (PRL) was seen in 90% of AD. IR-PRL and -VIP were present in rare GC. (c) In the case with Cushing's disease, 60% of AD and very few GC contained IR-adrenocorticotropin (ACTH) and beta lipotropin. Rare GC processes contained IR-SRIH. (d) In the case without pituitary hormone hypersecretion, PRL was localized in rare AD and GC. Pituitary hormone and neuropeptides were never colocalized in the same cells. No case displayed IR-neurophysins or -thyroliberin. Pituitary hormones were localized by ultrastructural immunogold labeling. These findings show that: (i) in three cases, pituitary hormones (PRL and ACTH), and, in one case, VIP could be localized in both adenomatous and ganglion cells; (ii) the pituitary hormone containing cells in the tumors could be related to the hypersecretory syndromes; (iii) intratumoral IR-VIP and -GRH might be involved in GH and PRL hypersecretion in the cases with acromegaly and amenorrhea-galactorrhea. PMID- 2922996 TI - Astrocytic infection in canine distemper virus-induced demyelination. AB - Acute canine distemper virus (CDV)-induced demyelinating lesions were examined with double-labelling immunocytochemistry simultaneously demonstrating CDV antigen and glial fibrillary acidid protein (GFAP) as marker for astrocytes. It was shown that 64% of all astrocytes within the demyelinating lesions were infected and that 95% of all infected cells counted in the lesions were astrocytes. These results suggest that the astrocyte is the main target for CDV and that astroglial infection may play an important role in the mechanism of demyelination. PMID- 2922997 TI - Effects of ageing and physical training on rat skeletal muscle. An experimental study on the properties of collagen, laminin, and fibre types in muscles serving different functions. AB - The purpose of the present investigation was to study the effects of both advancing age and life-long endurance training on the connective tissue and fibre composition of two types of rat skeletal muscle. In particular, additional evidence was sought on age- and training-induced transformations of muscle fibres, and on the significance of intramuscular collagen in muscle functioning. For this purpose a combined study of exercise and ageing throughout the life-span of the experimental animals was constructed. To gain a broad view of muscle responsiveness the muscle fibre types, the estimates of different biochemical and histological properties of collagen as well as of the passive mechanical properties of both a slow (m. soleus = MS) and a fast (m. rectus femoris = MRF) skeletal muscle were determined. The results can be summarized as follows: 1) The percentage of type I fibres in MS increased from about 60% in one-month-old rats up to about 90% in the untrained and almost 100% in the trained rats at ages between 4 and 10 months. In adult animals the proportion of type I fibres was significantly higher in the MS of the trained than untrained animals. In the slow area of MRF, the percentage of type IIA fibres increased from a mean value of below 40% in one-month-old rats to above 50% in the untrained and near to 70% in the trained rats at the age of 24 months. Correspondingly, the proportion of type IIB fibres decreased with both age and training. In both types of muscles, there was a tendency towards smaller cross-sectional areas for the predominant fibre type in the trained rats when compared to the untrained rats. Consequently, the long-term endurance training used did not reverse the age-related shift in muscle fibre composition but clearly accelerated the fibre transformation towards more fatigue-resistant muscle fibres with slower contractile speeds. Nevertheless, the slowing due to endurance training is not necessarily deleterious, as different mechanisms may be involved in these age- and training-related alterations. The former appears to involve degenerative changes in the neuromuscular system whereas endurance-type activity could assist in the maintenance of the low threshold neural activity important for the expression of slow contractile characteristics. 2) The slow postural soleus contained more collagen compared with the fast locomotor rectus femoris muscle. The concentration of total collagen as well as the area-fractions of both endomysium and perimysium were larger in MS than in MRF.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2922998 TI - Intrafascicular multi-unit recordings from the human infra-orbital nerve. AB - Intrafascicular micro-electrode recordings were made from the human infra-orbital nerve close to the infra-orbital foramen. The fascicular organization was studied and multi-unit activity from low-threshold mechanoreceptive afferents was recorded during tactile stimuli, vibration and facial movements. Attempts were also made to record C-fibre activity. Innervation zones corresponding to 66 fascicles were mapped with tactile stimuli on facial hairy skin and the red zone of the lip. Most of these fields were located on the upper lip, where they overlapped, indicating a high innervation density. The fields had a median size of 3.8 cm2. Skin indentation evoked dynamic on- and off-responses and a much less pronounced static discharge. The afferent double-peaked responses to an oscillating probe applied to the peri-oral region induced similar grouping of the EMG activity during sustained lip protrusion. Contraction of facial muscles and stretching of the skin evoked on- and off-responses, whereas the static discharge was less pronounced, especially during sustained stretching. The dynamic sensitivity to minor variations in contraction and stretching was high, and during normal facial movements, as in speech, there was a barrage of impulses originating from mechanoreceptors within large facial areas. Functional implications of these sensorimotor interactions are discussed. Sympathetic C fibre activity, frequently seen in recordings from the supra-orbital nerve, was never encountered in the infra-orbital nerve recordings, indicating a lack of such fibres. Failure to detect afferent C-fibre activity could be explained by methodological difficulties. PMID- 2922999 TI - Mechanoreceptive units in the human infra-orbital nerve. AB - Eighty-four low-threshold mechanoreceptive afferents innervating facial hairy skin or the red zone of the lip were recorded with micro-electrodes from the human infra-orbital nerve. Based on their responses to skin indentations, the units were classified as slowly or fast-adapting, with small or large receptive fields. The responses to hair movement, skin stretching and contraction of facial muscles were also studied. Both hairy skin and the red zone were innervated by slowly and by fast-adapting units. The innervation density was found to be highest at the corner of the mouth and on the upper lip. Slowly adapting units with small fields in hairy skin were most common and included units responding to sustained hair displacement. These units are suggested to have two types of end organs, either pilo-Ruffini endings or Merkel cell-neurite complexes. The slowly adapting units with large fields were spontaneously active stretch receptors and may have corresponded to Ruffini corpuscles, although the possibility of other, intramuscular, receptors could not be ruled out. Only one afferent possibly innervated a Pacinian corpuscle. Most mechanoreceptors were also activated by skin stretching or contraction of facial muscles. Many of the slowly adapting units with small fields responded to the onset and release of stretch, whereas their discharge in response to sustained stretching adapted more or less completely. Spontaneously active units had the most sustained stretch response. It is concluded that several types of cutaneous mechanoreceptors can operate as sensitive proprioceptors of importance for facial kinaesthesia and motor control. PMID- 2923000 TI - Sympathectomy provides evidence of dopamine storage in rat laryngeal nerve paraganglia. AB - Catecholamine content in the recurrent and superior laryngeal nerves (RLN and SLN) of the rat was analysed by high-performance liquid chromatography after surgical and chemical sympathectomy. Sympathectomy induced by repeated injections of guanethidine did not lead to any change in the dopamine (DA) level, whereas the noradrenaline (NA) content decreased by 68% and 64% respectively in the RLN and SLN. Surgical excision of the superior cervical ganglion (SCG) did not alter the level of DA in the SLN, but caused a 60% decrease of DA in the RLN. Removal of SCG did not affect the NA levels either in the RLN or in the SLN, unless it was combined with extirpation of the middle cervical ganglion, which induced a decrease in NA in both nerves. The results indicate that much of the DA in the laryngeal nerves is stored outside the sympathetic nerve fibres, probably in the small organs earlier characterized as endoneurial paraganglia. PMID- 2923001 TI - The rat epitrochlearis muscle: metabolic characteristics. PMID- 2923002 TI - Short-term effects of stimulus interval changes in guinea-pig and rat atrial muscle. AB - Isometric force and action potentials were recorded in thin atrial strips from guinea-pigs and rats (32 degrees C). The restitution of peak force and action potential duration, after a regular contraction, was determined (test interval 0.1-120 s), together with the post-extrasystolic potentiation. The mechanical restitution could be described with an exponential function in two phases as: force = A(I-e-k1t) + B(I-e-k2t). By increasing the basic stimulation rate in guinea-pig atria from 0.2 to 2 Hz, the size of A was approximately doubled while B was only slightly affected. When [Ca2+] was increased from 0.9 to 3.6 mmol l-1, the size of A increased approximately 3.4 times while B decreased only slightly. There was a close correlation between steady-state contractility of the muscle and parameter A but not parameter B. In a similar fashion post-extrasystolic potentiation can be described as: force = Ce-kt + D. This potentiation was greater in guinea-pig than in rat hearts. In both species the rate of potentiation decay (k) was usually similar to the rate of the first phase of restitution (k1). It seems reasonable to interpret the parameters A and B as reflections of two separate intracellular compartments for activator calcium. PMID- 2923003 TI - Metabolic control of large-bore arterial resistance vessels, arterioles, and veins in cat skeletal muscle during exercise. AB - The metabolic control of the vascular bed in cat gastrocnemius muscle during exercise was studied with a new technique (Bjornberg et al. 1988) permitting continuous and simultaneous recordings of arteriolar and capillary pressures, and of resistances in the following consecutive vascular section: proximal arterial resistance vessels greater than 25 microns, arterioles less than 25 microns, and on the venous side. The study thereby provided quantitative data for resistance and active intrinsic tone in these vascular segments at rest, during graded exercise vasodilatation, and in the post-exercise period. Slight activation of the metabolic control system by low-frequency somatomotor nerve stimulation ('light exercise') caused inhibition of intrinsic tone and decreased vascular resistance selectively in the arteriolar section. At increasing workloads, arteriolar resistance was further decreased, but resistance and tone in the proximal arterial resistance vessels and the veins then became clearly reduced as well. This difference in effectiveness of the metabolic control system on the different segments of the vascular bed was expressed quantitatively in terms of a 'metabolic vasodilator index'. Graded activation of the metabolic control system led to a marked segmental redistribution of intrinsic vascular tone, in turn resulting in an increased pressure drop across the proximal arterial vessels in the veins and a decreased pressure drop over the arterioles. The observed decrease in the pre- to post-capillary resistance ratio caused, at a constant arterial pressure of 100 mmHg, a graded increase in capillary pressure with increasing workloads, at maximum vasodilatation by an average value of 14 mmHg above the resting control value of 15.4 +/- 0.6 mmHg. In the post-exercise period, recovery of vascular tone to control was more rapid in the proximal arterial resistance vessels and the veins than in the arteriolar segment. PMID- 2923004 TI - Antidepressant withdrawal syndromes: phenomenology and pathophysiology. AB - The literature reporting signs and symptoms produced by the abrupt or gradual withdrawal of antidepressants is reviewed. Patients with antidepressant withdrawal syndromes are presented and principles governing their care are highlighted. Finally, the author summarizes evidence that antidepressant-induced supersensitivity of central and peripheral muscarinic cholinergic mechanisms may account for commonly observed antidepressant withdrawal phenomena. PMID- 2923005 TI - Acute changes in cerebral blood flow associated with marijuana smoking. AB - Cerebral blood flow (CBF) was measured in experienced (ES) and inexperienced (IS) marijuana smokers with the 133xenon inhalation technique before and after smoking both a high-potency marijuana cigarette and a placebo marijuana cigarette. CBF was measured twice under resting conditions in a control group. Mood states before and after marijuana smoking were quantified with the Profile of Mood States (POMS). Analyses of POMS factors after smoking marijuana revealed IS had an increase in anxiety while ES had a decrease. IS also had a significant increase in depression and decrease in vigor, but neither variable changed in the ES. After marijuana, CBF decreased in IS, but in ES, it increased in comparison with the 2 control runs. In both IS and ES, CBF changes following placebo administration were similar to those associated with marijuana smoking. However, in IS, the marijuana-induced CBF decrease was significantly higher than that associated with placebo. There were no statistically significant differences between the CBF increase seen after placebo and marijuana in ES. Anxiety, anger, fatigue, confusion and depression had significant negative correlations with CBF while vigor correlated positively, but the anxiety factor was the only one to account for a significant percentage of the change (parital correlation) in hemispheric CBF. PMID- 2923006 TI - Explorative single-blind study on the sedative and hypnotic effects of buspirone in anxiety patients. AB - In this single-blind study the sedative and hypnotic properties of buspirone, a nonbenzodiazepine anxiolytic, were investigated in 8 anxious outpatients. Polysomnographic recordings were gathered during baseline, at the start of active medication, after 3 weeks of treatment and one night after discontinuing treatment. Daytime alertness was measured using the Multiple Sleep Latency Test and performance tests. The effects of buspirone on sleep structure were minimal and of no clinical consequence. Subjectively, the patients reported improved sleep quality. There were no effects on daytime alertness at the beginning, after 3 weeks or at sudden discontinuation of the medication. It is concluded that buspirone does not have a sedative or hypnotic effect in anxiety patients. PMID- 2923007 TI - Prevalence of psychiatric disorders in Taiwan defined by the Chinese Diagnostic Interview Schedule. AB - The Taiwan Psychiatric Epidemiological Project, conducted from 1982 to 1986, used the multistage random sampling method with 5005, 3004 and 2995 subjects selected respectively from metropolitan Taipei (MT), 2 small towns (ST) and 6 rural villages (RV). The case identification tool was the Chinese modified Diagnostic Interview Schedule (DIS-CM). This study presents the lifetime and one-year prevalence of 27 and of 17 specific psychiatric disorders respectively. The lifetime prevalence of any disorder defined by the DIS-CM -- excluding tobacco dependence -- was 16.3%, 28.0% and 21.5% in the MT, ST and RV samples respectively. The differences in lifetime prevalence between the sexes and between the 3 sampling areas were significant for 15 and 8 disorders respectively. The ST sample seemed to have the most disorders, with the highest prevalence among 3 sampling areas. The mean ratio of one-year to lifetime prevalence was 0.67. The differences in prevalence rates between the 3 sampling areas and between the international studies are discussed from methodological, social and cultural points of view. PMID- 2923008 TI - Depression among general hospital patients in Greece. AB - We estimated the prevalence of depression in 150 medical and surgical inpatients. Forty-three patients (29%) scoring at 14 or above on the Beck Depression Inventory (BDI) were classified as depressed. An excess of women and white-collar workers and more stressful life events during the last 12 months were found among the depressed patients. Of the 21 BDI items, 6 differentiated the 43 medical surgical depressed patients from a group of 43 psychiatric inpatients with a diagnosis of primary or secondary depression (Feighner's criteria). Medically ill depressed patients scored higher in social withdrawal, work inhibition and irritability but lower in loss of libido, sleep disturbance, and lack of satisfaction. Our results show rates of depression in a medical inpatient population in Greece comparable with those in other studies. The use of BDI may help assessment of depression in general hospital patients. PMID- 2923009 TI - Use of mental health services in south Verona and Groningen. A comparative case register study. AB - A comparison was made of the utilization of mental health services in a psychiatric case register area in Italy (south Verona) and one in the Netherlands (Groningen). All residents living in these areas who contacted a mental health service in 1982 were traced and followed for a period of one year. The year prevalence rates differed considerably (110/10,000 in south Verona and 329/10,000 in Groningen). Rates of single consulters were similar in both areas, while those of chronic inpatients were more than 11 times higher in Groningen than in south Verona. After excluding both single consulters and chronic inpatients, when comparing service consumption according to fixed classes of scores, the category of highest service use accounted for 60% of care provided in Groningen as compared with less than 30% in south Verona. The proportion of total service consumption due to inpatient care was about the same in both areas, but brief admissions were more common in south Verona. Moreover, when service use was considered as a relative construct, about 10% of patients in both areas could be called high users. Finally, long-term patients were more prevalent in Groningen (26%) than in south Verona (13%). PMID- 2923010 TI - Regional differences in mortality from dementia in Australia: an analysis of death certificate data. AB - Australian death certificate data were analysed to determine whether they can provide useful information on regional differences in the prevalence of dementia. Strong differences between the Australian states were found in the prevalence of dementing disorders at death. However, evidence indicated that death certification practices influenced the prevalence rates found: a) the reported prevalence of various dementing disorders at death has changed greatly over quite a short period; b) the prevalence of dementing disorders at death was more strongly influenced by place of death than by place of birth; and c) the differences between states were a result of very high rates in particular regions which, in one case, could be traced to the death certification practices of a single medical practitioner. It is concluded that death certificate data are not useful for investigating regional differences in the prevalence of dementia. PMID- 2923011 TI - Blood serotonin levels in suicidal schizophrenic patients. AB - A decrease in central serotonin metabolism has been found in suicidal patients. In schizophrenic patients suicidality is predominantly observed as a transient phenomenon being most pronounced during an acute psychotic episode. We investigated blood serotonin levels as a paradigm for serotonin metabolism in suicidal schizophrenic women who were psychotic and compared their data with those of nonsuicidal psychotic schizophrenic women and healthy controls. Blood serotonin was lower in suicidal female schizophrenic patients (0.44 +/- 0.05 mumol/l, n = 17) than in nonsuicidal female schizophrenic patients (0.94 +/- 0.07 mumol/l, n = 17; P less than 0.001) or in healthy women (0.90 +/- 0.02 mumol/l, n = 26; P less than 0.001). These findings support the hypothesis that decreased serotonin metabolism may be associated with suicidal behavior in schizophrenic women. PMID- 2923012 TI - The prevalence of dementia as measured by the Cambridge Mental Disorders of the Elderly Examination. AB - General practice patients aged 75 years and over were screened for cognitive impairment using the Mini-Mental State Examination. Those scoring 23 or below and a sample of those scoring 24 or 25 were assessed using the Cambridge Mental Disorders of the Elderly Examination (CAMDEX), a structured interview schedule specifically designed to detect mild dementia. The CAMDEX includes a mental state examination, a psychiatric history, detailed cognitive testing and an information interview. The prevalence of dementia in 2311 patients was found to be 10.5%, about half that found in most earlier studies. Possible reasons for this low rate are discussed. PMID- 2923013 TI - Some characteristics of the psychiatric population attending a primary care centre in Kuwait. AB - This study examined the sociodemographic correlates of psychiatric illness in a primary care centre in Kuwait. A total of 164 psychiatric patients seen over a 3 year period formed the experimental group while 165 nonpsychiatric patients attending the same centre formed the control group. Results showed significant differences in basic demographic variables of the 2 groups. The psychiatric patients were significantly more likely to be single, unskilled, young, less educated and living alone or in an overcrowded household and to report more recent life events than controls. The absence of family and social support, lacking a meaningful job and chronicity of illness were significantly correlated with poor treatment response. Possible interpretations of the results were discussed in the cultural context of our patients. The fact that 57% of the psychiatric patients had been ill for more than 6 months prior to consultation highlights the importance of orientation of primary care practitioners to the psychiatric aetiology of somatic presentation of many of their patients. PMID- 2923014 TI - Phenomenology and pathophysiology of antipsychotic withdrawal symptoms. PMID- 2923015 TI - Anxiety. PMID- 2923016 TI - Feasibility of sigmoidoscopic screening for bowel cancer in a primary care setting. AB - Sigmoidoscopic screening for bowel cancer is controversial because of its debatable efficacy, lack of patient and physician acceptance of the procedure, and uncertainty about its practicality with the large numbers of patients in primary care settings. This study addressed patient acceptance and practicality. During an 18-month period, 75 percent of all patients aged 50 years and greater who were seen for health maintenance accepted sigmoidoscopy. The procedure was integrated into office routines without disrupting other patient care. While compliance with fecal occult blood testing was high (88 percent), sensitivity of this test for neoplastic polyps within reach of the proctosigmoidoscope was low (11 percent). These results suggest that acceptance of sigmoidoscopy by patients seen in family physicians' offices could be greater than has been anticipated. PMID- 2923017 TI - Obstetric care in a rural family practice. AB - Obstetrical care in the United States is becoming more difficult for rural populations to obtain. Fewer family physicians are providing obstetrical services. This study is a report of one family physician's obstetric experience in a small rural town. In a series of 67 obstetrical patients, 8 percent of the deliveries occurred outside of the hospital. The rate of Cesarean section was 3 percent, significantly less than the greater than 20 percent national average. There was 1 premature delivery, and no infant deaths. These figures compare well with national averages and show the need for family physicians to provide obstetrical care in rural areas. PMID- 2923019 TI - Pleural effusion and hydronephrosis in a newborn. AB - While the association of obstructive uropathy with ascites has been known since 1863, and with pleural effusion since 1954, the latter combination remains rare. This case report describes a male newborn with a massive left pleural effusion that was caused by same-sided hydronephrosis from obstructing posterior urethral valves. The effusion disappeared within a few days after adequate urinary drainage was established, and the infant was remained well since the abnormal urethral valves were fulgurated cystoscopically. Review of the clinical and experimental literature reveals no consensus about how pleural fluid accumulates in the presence of obstructive uropathy, and this neonate showed a direct inverse relation between the amount of pleural fluid drainage and urinary output via catheter. Hydronephrosis should be considered diagnostically when a newborn has a pleural effusion that is otherwise unexplained. PMID- 2923018 TI - The consultant family physician. AB - Family physicians frequently consult and refer to other specialists, both generalist and subspecialist. Less commonly has the family physician been used as a consultant. A randomized questionnaire survey of family physicians in five midwestern states was used to consider the frequency and reasons for other specialists collaborating with the family physician as a consultant. Fifty percent of the respondents consult and refer to as well as receive consultations/referrals from other family physicians. Thirty-five percent of the respondents receive consultations and referrals from other generalist specialists, and 28 percent receive theirs from subspecialists. Most often these occur because the patient has no family physician, but family physicians are also used for their procedural skills and coordination of patient evaluation and management, including preoperative evaluation of patients. This study confirms that the consultant family physician is an important part of the health care team. PMID- 2923020 TI - Seeing over one's shoulder and out of the corner of one's eye. PMID- 2923023 TI - Medical manpower in Alabama: shortage, sufficiency or surfeit? PMID- 2923021 TI - Flexible sigmoidoscopy. PMID- 2923022 TI - Adoption. PMID- 2923024 TI - The tragedy of trauma. PMID- 2923025 TI - Life? PMID- 2923026 TI - Herpes simplex of the nipple: infant-to-mother transmission. AB - Intrafamilial spread of herpes simplex is a recognized problem. A case is presented in which a 15-month-old child was infected by a five-year-old sibling with presumed gingivostomatitis. The young child then transmitted symptomatic herpes infection to both maternal nipples during breast feeding. Although mouth to-breast transmission of herpes simplex virus may be rare, it is appropriate to advise breast-feeding mothers of children with herpes gingivostomatitis of this possibility. PMID- 2923027 TI - Pseudoparasitism with Gordius robustus. AB - The Gordius worm is a parasite of crickets and other arthropods, but not of humans. In almost all cases, the association between humans and the Gordius species, such as Gordius robustus, is purely coincidental. Gordius pseudoparasitism must be distinguished from true helminthic disease to alleviate patient anxiety and to avoid an unnecessary course of antihelminthics. PMID- 2923028 TI - Recurrent toxic shock syndrome. AB - While the classic manifestations of toxic shock syndrome in a high-risk patient are readily recognized, probable cases of the syndrome are often overlooked. This is especially true of nonmenstrual toxic shock syndrome, which may be associated with a variety of clinical conditions. There is a 30 percent risk of recurrence following the first episode of toxic shock. The roles of prophylactic antibiotics and oral contraceptives in reducing recurrences require further study. PMID- 2923029 TI - Pruritic folliculitis of pregnancy. AB - Pruritic folliculitis of pregnancy may appear any time after the fourth month of gestation. This distinct dermatosis is characterized by pruritus and small, follicle-centered, erythematous papules that may be excoriated or may have the appearance of small pustules. Distribution is variable, although all reported cases have included the abdomen. There is an absence of systemic maternal or fetal toxicity, and the condition resolves spontaneously after delivery. The cause of this dermatosis is unknown. PMID- 2923030 TI - Arnold-Chiari malformation: a diagnostic challenge. AB - Arnold-Chiari malformation is a disorder of embryologic development. In Type I, there is cerebellar displacement into the spinal canal, but hydrocephalus and syringomyelia are variable. Type II usually is manifested by severe hydrocephalus and myelomeningocele in infancy. Type I malformations may pose diagnostic challenges because they often produce bizarre and vague symptoms. A careful history and physical examination, coupled with neurologic testing, especially magnetic resonance imaging, will lead to the correct diagnosis. PMID- 2923031 TI - Use of a hearing assistance device in nursing homes. AB - An inexpensive hearing assistance device can improve communication with nursing home residents. In patients who do not have prescribed hearing aids or who are being audiologically evaluated, voice amplification with such a device facilitates initial assessment as well as ongoing care. Such devices are available at local consumer outlets for under $30, making them available to persons who are unable to afford more sophisticated models. PMID- 2923032 TI - An algorithm for corticosteroid withdrawal. PMID- 2923033 TI - High-altitude illness. PMID- 2923034 TI - Newborn circumcision. PMID- 2923035 TI - Trauma. PMID- 2923036 TI - AAP issues statement on perinatal HIV infection. PMID- 2923037 TI - Five-minute HIV test now available. PMID- 2923038 TI - Satisfaction with board certification in nuclear pharmacy. PMID- 2923039 TI - It's time to take the next step. PMID- 2923040 TI - Commitment to the profession of pharmacy: are there sex differences? PMID- 2923041 TI - APhA year in review. PMID- 2923042 TI - Opening and positioning a pharmacy for success, Part 1. PMID- 2923043 TI - One price for all. PMID- 2923044 TI - Policy committee work challenges members. PMID- 2923045 TI - State of the profession. PMID- 2923046 TI - A symposium: Myocardial ischemia--current status and future directions. June 12 14, 1987, Kyoto, Japan. Proceedings. PMID- 2923047 TI - Effects of nifedipine on left ventricular distensibility, relaxation and filling dynamics during pacing-induced myocardial ischemia. AB - Diastolic left ventricular properties were assessed in 8 patients with coronary artery disease at rest and during postpacing states before and after nifedipine (10 mg sublingually). Typical anginal pain developed in all patients during pacing tachycardia before but not after nifedipine. Postpacing increases in end diastolic pressure (10 +/- 5 [mean +/- standard deviation] to 23 +/- 9 mm Hg) and volume (99 +/- 29 to 113 +/- 27 ml) were greatly attenuated with nifedipine (13 +/- 7 and 97 +/- 22 ml, respectively). These responses were associated with normalization of postpacing shifts of the ventricular diastolic pressure-volume curve upward or more to the right. The time constant of ventricular relaxation was prolonged by pacing tachycardia (44 +/- 10 to 62 +/- 5 ms) and was reduced to the control level in postpacing beats after nifedipine. The peak rate of early ventricular filling was affected neither by pacing stress nor by nifedipine. When regional myocardial function was expressed by a radial coordinate system, the nonischemic segment responded to the control pacing with an increase in end diastolic length and comparable augmentation of the stroke excursion, while the ischemic segment showed a marked reduction in stroke excursion with end-diastolic length unchanged. Thus, the diastolic pressure-length relation moved up to the higher portion of the single curve in the nonischemic segment, while it shifted directly upward in the ischemic segment. These responses were markedly attenuated with nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2923048 TI - Angiographic observations and clinical relevance of coronary thrombus in unstable angina pectoris. AB - To assess the mechanisms of unstable angina, the coronary angiographic studies in 69 patients with severe unstable angina (prolonged pain or pain at rest) and in 20 patients with stable angina were blindly reviewed to assess the coronary morphologic changes in these syndromes. Coronary angiography was performed an average of 1.7 days from admission and an average of 24 hours from last symptoms of chest pain in patients with unstable angina. Angiographic studies were analyzed for evidence of coronary thrombus (intraluminal filling defects) at significant stenoses in patent vessels or thrombus at sites of total occlusion) and for coronary lesion morphology suggesting a complex or acute lesion (irregular or ill-defined margins, inhomogeneity, haziness or ulceration). Angiographic evidence of coronary thrombus was present in 40 of 69 patients (58%) with unstable angina: 31 (45%) had intraluminal filling defects and 9 (13%) had thrombotic total occlusion with well-developed collaterals present. Only 1 of 20 patients (5%) with stable angina had evidence of thrombus (p less than 0.001). Complex lesions were present in 18 other unstable patients (26%) and in 2 other patients (10%) with stable angina who did not have angiographic evidence of thrombus. Overall, 58 of 69 patients (84%) with unstable angina had morphologic findings suggesting an acute process (thrombus or complex lesion) compared with 3 of 20 patients (15%) with stable angina, p less than 0.0001. Thus, unstable angina is associated with a high prevalence of angiographic coronary thrombus and complex lesions suggesting an acute process, in contrast to stable angina.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2923049 TI - Acceleration of cell necrosis following reperfusion after ischemia in the pig heart without collateral circulation. AB - A study of whether reperfusion accelerates cell death was performed in 35 pig hearts without collateral circulation. In 15 animals, the distal one-third of the left anterior descending coronary artery was occluded for 1 hour followed by 1-, 3-, or 7-hour reperfusion in 5 animals each. As controls, 5 hearts each were examined after 1, 2, 4 and 8 hours of occlusion of the artery without reperfusion. Heart rate and aortic pressure before and during occlusion and reperfusion did not change in any group. The subepicardial and subendocardial regional blood flow decreased to almost zero in all hearts after occlusion (85 +/ 1 to 2 +/- 2) but recovered during reperfusion (65 +/- 15 ml/100 g/min). Specimens were histologically examined by an enzyme method using nitrotetrazolium blue, an immunohistochemical method using myoglobin antibody, by staining with hematoxylin-eosin and Masson's trichrome. In the control hearts, clear demarcation of the infarct area was observed 4 hours after occlusion. However, in the reperfusion group, clear demarcation of the infarct was seen after 1-hour reperfusion, namely, 2 hours after the onset of infarct. Demarcation was seen not only in the tissue with contraction band necrosis, but also in the tissue with coagulation necrosis. Therefore, it is concluded that reperfusion accelerates cell death due to both contraction band necrosis and coagulation necrosis. PMID- 2923050 TI - Enhanced responsiveness of smooth muscle, impaired endothelium-dependent relaxation and the genesis of coronary spasm. AB - Pathophysiology and genesis of coronary artery spasm were examined in vivo and in vitro in Gottingen miniature pigs. Five of 36 consecutive pigs before endothelial denudation showed evidence of regional hyperconstriction after intracoronary administration of histamine (group 1). Histologic examination revealed intimal thickening along the spastic site. Because 5 pigs died during endothelial denudation, cholesterol feeding was randomly assigned to 13 of the remaining 26 pigs (group 2) and others were fed a regular low cholesterol diet (group 3) for 3 months. Regional coronary hyperconstriction was also evident after intracoronary administration of histamine at the site of denudation, and the degree of constriction was 78 +/- 3 and 74 +/- 4% in groups 2 and 3, respectively. Because the intimal thickening was confirmed at the site of spasm in groups 2 and 3, spontaneous as well as denudation-induced intimal thickening accompanied the enhanced responsiveness to histamine, irrespective of the level of serum cholesterol. However, the role of geometry on histamine-induced luminal narrowing was only 6% and was not physiologically significant. Augmented responses of the coronary artery to histamine, but not to phenylephrine or potassium chloride were reproduced in the nonbeating isolated heart preparations perfused at 90 mm Hg with oxygenated Krebs-Henseleit solution, and the degree and location of in vitro hyperconstriction were similar to that in vivo and were not attenuated after pretreatment with the nerve transmitter blockers, guanethidine (3 X 10(-6) M), atropine (10(-6) M) and tetrodotoxin (3 X 10(-7) M). Accordingly, spasm can be provoked without the influence of blood constituents and neural factors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2923051 TI - Effects of afterload elevation on the ischemic myocardium in isolated, paced canine heart with partial coronary stenosis. AB - The effect of afterload elevation on the ischemic myocardium was examined in an isolated, paced canine heart with a partial coronary stenosis. The coronary blood flow of the left circumflex coronary artery was reduced to approximately one third of the values before stenosis. The left circumflex coronary stenosis produced a decrease in global ventricular function, a decrease in systolic shortening and deviation of the ST-segment of the epicardial electrocardiogram and an increase in myocardial carbon dioxide (CO2) tension of the ischemic region. Then, afterload elevation with constant preload decreased the myocardial CO2 tension and improved the ST-segment deviation of the ischemic myocardium. Mechanical function, estimated by the relation between mean aortic pressure and systolic shortening, also improved with elevation of mean aortic pressure. In contrast, afterload elevation combined with preload elevation did not improve ischemic injury, as estimated by myocardial CO2 tension, and did not improve ST segment deviation or mechanical function despite an increase in left circumflex coronary flow. These results suggest that the elevation of afterload pressure under constant preload improves ischemia produced by a partial coronary stenosis due to increased coronary blood supply; however, the preload elevation counterbalances the beneficial effects of afterload elevation. PMID- 2923052 TI - Usefulness of negative dP/dt upstroke pattern for assessment of left ventricular relaxation in coronary artery disease. AB - It has been reported that regional asynchrony due to acute ischemia disturbs the exponential nature of left ventricular (LV) pressure reduction and may alter the pattern of (-)dP/dt upstroke curve. If LV pressure decreases exponentially during the isovolumic relaxation period (P = Ae-t/T + B, where A and B = constants, t = time and T = time constant), the (-)dP/dt upstroke curve should also be exponential and upward-convex because dP/dt = A(-t/T)e-t/T. To test this theory in humans, the LV (-)dP/dt upstroke curve was analyzed in 9 normal subjects, 12 patients with effort angina pectoris (AP) and 15 with old myocardial infarction (MI) under the basal conditions. The (-)dP/dt upstroke was convex-upward in all normal subjects, but convex-downward in 9 of 12 patients with AP and in all patients with MI, which suggests nonexponential decrease in LV pressure in the groups with AP and MI. The dP/dt (20/60), which is the ratio of the (-)dP/dt value at 20 ms after peak (-)dP/dt to that at 60 ms after peak (-)dP/dt, was significantly lower in the group with AP (1.70 +/- 0.07) and in the group with MI (1.61 +/- 0.13) than in normal subjects (2.08 +/- 0.18) (p less than 0.005). This indicates that (-)dP/dt upstroke 20 to 60 ms after peak (-)dP/dt increases more slowly in the groups with AP and MI than in normal subjects. Theoretical consideration showed that such a slower increase of the upstroke resulted from impaired early to midrelaxation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2923053 TI - Reperfusion-induced calcium gain after ischemia. AB - Reperfusion-induced calcium gain provides a marker of irreversible injury, but whether the cells gain calcium because of irreversible injury caused by the ischemic episode, or whether it is the reperfusion-induced calcium gain that triggers the irreversible injury has yet to be established. Using isolated rat hearts made ischemic for either 30 or 60 minutes, and reperfusing with Krebs Henseleit buffer or Krebs-Henseleit buffer containing either 2,3-butanedione monoxime (to inhibit contractile activity) or 2,4-dinitrophenol or nitrogen gassed substrate-free Krebs-Henseleit buffer (to inhibit oxidative phosphorylation), the effect of reperfusion was monitored in terms of calcium gain and ultrastructural changes including loss of sarcolemmal integrity. The results establish that the routes of calcium entry during postischemic reperfusion are complex. The calcium gain can occur in the absence of mitochondrial oxidative phosphorylation and is modulated by interventions introduced at the moment of reperfusion which affect the contractile state. There are at least 2 routes of calcium entry: contraction-dependent and contraction independent. The former is probably associated with the development of sarcolemmal discontinuities. The results also establish that when sarcolemmal integrity has been destroyed, the cells can gain excess calcium under conditions that prevent mitochondrial calcium uptake. Accordingly, the mitochondria cannot be the only intracellular organelles that accumulate calcium under these conditions. Additional studies are needed to identify the other sites of calcium binding under conditions of adenosine triphosphate deprivation. PMID- 2923054 TI - Alterations in left ventricular relaxation, early diastolic filling and passive viscoelastic properties during postpacing ischemia. AB - Alterations in left ventricular relaxation, early diastolic filling, regional myocardial dynamics and passive viscoelastic properties during postpacing ischemia were studied in 9 patients with coronary artery disease. In all patients typical anginal pain developed during pacing tachycardia, and in the postpacing beat, left ventricular end-diastolic pressure increased from 14 +/- 4 to 26 +/- 5 mm Hg (mean +/- standard deviation, p less than 0.01), relaxation time constant increased from 44 +/- 9 to 59 +/- 7 ms (p less than 0.01) and ejection fraction diminished from 63.1 +/- 9.1 to 52.8 +/- 10.8% (p less than 0.01). However, peak rate of early left ventricular filling obtained from frame-by-frame analysis of left ventriculograms did not change significantly. The time difference from segmental peak lengthening to left ventricular peak filling increased significantly in the ischemic segment (32 +/- 30 vs 77 +/- 49 ms, p less than 0.05). Chamber stiffness constant of a viscoelastic model increased significantly from 0.0177 +/- 0.01 to 0.0354 +/- 0.015 (p less than 0.01) without change in chamber viscosity constant. In the ischemic segment, peak rate of lengthening decreased by 45% with ischemia, and peak rate of lengthening normalized for the end-diastolic segment length by 36%. However, peak rate of lengthening normalized for the extent of systolic shortening did not change. The control segment showed a tendency to increase in these 3 parameters, but the changes were not statistically significant. Thus, peak rate of segmental myocardial lengthening decreased with ischemia because of a decrease in segmental shortening.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2923055 TI - Evolution of late potential activity in the first six weeks after acute myocardial infarction. AB - The evolution of surface ventricular late potential activity was studied in 50 patients during the 6 weeks after first acute myocardial infarction (AMI). In 15 of 47 patients (32%) late potential activity appeared within 6 hours of the onset of major symptoms. Its prevalence overall remained approximately 30% at each recording time but with marked individual variability in appearance. Late potential activity was associated with late ventricular arrhythmias (greater than 24 hours after AMI) but not with early ventricular arrhythmias (less than 24 hours after AMI). Late ventricular arrhythmias or sudden death occurred only in the 6 patients with late potential activity (p less than 0.05). Early ventricular fibrillation (15 patients) occurred equally in the patients with and without late potential activity. Thus, late potential activity occurs at some stage in the first 6 weeks after AMI in 50% of patients, but its timing is variable. It is a sensitive but not specific predictor of late ventricular arrhythmias and sudden death, but not of early ventricular fibrillation. PMID- 2923056 TI - Rapid serial enzyme measurements in evaluation of patients with suspected myocardial infarction. AB - Because clinical and laboratory criteria cannot accurately establish the presence or absence of acute myocardial infarction (AMI) at the time of initial presentation, this diagnosis is not confirmed in the majority of patients admitted to coronary care units. To study the effectiveness of serial changes in enzyme activity in specimens taken at presentation and 8 hours later in establishing the likelihood of AMI, the results in 1,214 patients with acute cardiac symptoms of less than 24 hours' duration were retrospectively evaluated. In 1,007 patients with initially normal creatine kinase (CK), an increase in CK (positive delta-CK) occurred in 98% of patients with AMI and 16% of patients without AMI. In 196 patients with elevated total CK, a low ratio of CK to aspartate aminotransferase was found in 98% of patients with AMI and 33% of patients without AMI. These 2 enzyme ratios had a sensitivity greater than 90% in patients with typical and atypical histories. The overall predictive value of serial enzyme measurements for AMI was 53%, compared with 18% in patients selected for admission. These results suggest that serial enzyme measurements could be used in the initial evaluation of patients with suspected AMI, and have the potential to reduce the number of patients admitted to coronary care units who do not have AMI. PMID- 2923057 TI - Paradoxical elevation of threshold to angina pectoris by cold pressor test in men with significant coronary artery disease. AB - Patients with coronary artery disease (CAD) have angina pectoris at varying levels of myocardial oxygen demand. Fluctuations in coronary blood supply due to dynamic changes in coronary vasomotor tone are believed to be responsible for this variation in angina threshold. Cutaneous cold application produces an inappropriate increase in coronary vascular resistance in patients with CAD. To assess the effect of a coronary vasoconstrictor stimulus during exercise (when there are competitive stimuli for coronary dilatation), 16 men with documented CAD and angina underwent 2 exercise tolerance tests, 1 performed for control purposes and the other during cold application (hand and forearm immersed in ice). The cold pressor test elicited an increase in systolic blood pressure at rest (134 vs 159 mm Hg, p less than 0.02) at the end of stage I (145 vs 165 mm Hg, p less than 0.02) and at peak exercise (154 vs 166 mm Hg, p less than 0.05). The diastolic pressure was similarly increased during cold pressor exercise test, but the heart rate showed little or no change. Most patients (11 of 16) tolerated equal or greater double products (heart rate X systolic pressure X 10(-3) at angina (17 vs 20, p less than 0.02), 1-mm ST-segment depression (16 vs 18, p less than 0.05) and peak exercise (18 vs 20, p less than 0.08) during cold pressor exercise test as compared with the baseline exercise test, without a reduction in exercise capacity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2923058 TI - Multivariate analysis of the twenty-year follow-up of the Donolo-Tel Aviv Prospective Coronary Artery Disease Study and the usefulness of high density lipoprotein cholesterol percentage. AB - The aim of this study was to assess the role of high density lipoprotein (HDL) cholesterol percentage and its relation to other variables assumed to be coronary risk factors. The 20-year follow-up involved 2,633 presumably healthy subjects, 1,308 men and 1,325 women, aged 25 to 69 years at the beginning of the study in 1964. Variables determined at entry examination included total cholesterol, HDL cholesterol, systolic and diastolic blood pressures, body mass index and cigarette smoking. During the 20-year period there were 242 fatal and nonfatal definite coronary events in men, and 108 in women. All variables differed in varying degrees between subjects who did and did not have a definite coronary event. Three multiple logistic regression models revealed that among these variables the most important was HDL-cholesterol percentage, which significantly improved the regression, even after total cholesterol was included with all other risk factors. With the first model, goodness-of-fit tests indicated that predicted values fit the observed values well, even after the first step, if HDL cholesterol percentage is entered. The second and third models significantly fit the predicted values only after entering the HDL-cholesterol percentages. This means that although all the other variables, including total cholesterol, differed significantly between the affected and nonaffected groups, they were insufficient predictors alone. The results reveal that HDL-cholesterol percentage had the highest predictive value for risk of future coronary disease; it significantly improved the predictive capability of the logistic regression model, even after adjustment for all other mentioned variables.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2923059 TI - Prevalence and hemodynamic correlates of malnutrition in severe congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. AB - Whereas cardiac cachexia is well recognized, the frequency and hemodynamic correlates of malnutrition in severe congestive heart failure (CHF) have not been established. Anthropometric and serum albumin assessment of nutritional status was compared with hemodynamic, echocardiographic and serum chemistry evaluation in 48 patients with severe CHF (ejection fraction 0.17 +/- 0.05). Malnutrition, as defined by decreases in percent body fat determined from skinfold thicknesses, weight/height index or serum albumin, was present in 24 of 48 (50%) patients, who did not differ from the 24 well-nourished patients in cardiac index (1.9 +/- 0.6 vs 2.1 +/- 0.6 liters/min/m2) and pulmonary artery wedge pressure (30 +/- 6 vs 27 +/- 10 mm Hg), but had higher right atrial pressure (16 +/- 5 vs 9 +/- 6 mm Hg, p less than 0.01) and more severe tricuspid regurgitation by semiquantitative Doppler grading on a 0 to 3 scale (2.0 +/- 0.9 vs 0.9 +/- 0.8, p less than 0.01). Right atrial pressure was the only independent hemodynamic predictor of malnutrition (p less than 0.0002). Malnourished patients had lower serum sodium (134 +/- 4 vs 139 +/- 4 mEq/liter, p less than 0.01) and total triiodothyronine levels (89 +/- 30 vs 115 +/- 26 ng/dl, p less than 0.01) and higher creatinine levels (1.6 +/- 0.7 vs 1.2 +/- 0.4, p less than 0.03). None of the other biochemical markers of nutritional status differed between the groups except lower serum triglyceride levels (115 +/- 73 vs 186 +/- 97 mg/dl, p less than 0.05) in malnourished patients. Malnutrition is common in patients with severe CHF and is associated with increased right atrial pressure and tricuspid regurgitation. PMID- 2923060 TI - Increased complications and prolonged hospital stay in elderly cardiac surgical patients with low serum albumin. AB - Cardiac surgery in elderly patients is associated with acceptable operative mortality but an increased complication rate. Malnutrition is common in the elderly and may adversely affect surgical outcome. To determine the effect of hypoalbuminemia on postoperative complications, 92 patients greater than or equal to 75 years (range 75 to 90) undergoing a variety of major cardiac surgical procedures were evaluated. Thirteen patients (14%) had a serum albumin level less than 3.5 g/dl preoperatively. Compared to patients with normal albumin, hypoalbuminemic patients had an increased frequency of postoperative confusion, congestive heart failure, low cardiac output, renal dysfunction and gastrointestinal complications (all p less than 0.05). Mean postoperative length of stay was markedly prolonged in these patients (27 vs 12 days; p less than 0.001), and mortality also tended to be higher (31 vs 13%; p = 0.11). Using multivariate analysis, albumin less than 3.5 g/dl was the most powerful predictor of postoperative renal dysfunction (p less than 0.01), and was also an independent predictor of increased length of stay (p less than 0.01) and gastrointestinal disorders (p less than 0.05). Thus, hypoalbuminemia is a powerful indicator of an increased risk of perioperative complications in elderly patients undergoing cardiac surgery. Increased attention to nutritional factors is warranted in these patients. PMID- 2923061 TI - Mutations in the apolipoprotein B-100 gene: an important underlying cause of familially transmitted hypercholesterolemia and premature arteriosclerosis? PMID- 2923062 TI - Anticoagulation for cardioversion of atrial fibrillation. PMID- 2923063 TI - Doppler-detected tricuspid, mitral or aortic regurgitation in end-stage renal disease. PMID- 2923064 TI - Morphologic changes in coronary artery seen late after endarterectomy. PMID- 2923065 TI - Anomalous origin of four coronary ostia from the right sinus of Valsalva. PMID- 2923066 TI - Late recurrent rupture of a sinus of Valsalva aneurysm. PMID- 2923068 TI - Closed mitral commissurotomy is not obsolete in developed countries. PMID- 2923067 TI - Morbidity associated with anomalous origin of the left circumflex coronary artery from the right aortic sinus. PMID- 2923069 TI - Preoperative prediction of significant coronary artery disease in patients with valvular heart disease. PMID- 2923070 TI - A hitherto neglected cause of myocardial infarction associated with normal coronary arteries: chronic Chagas' heart disease. PMID- 2923071 TI - Body composition changes assessed by bioelectrical impedance measurements. AB - Twelve healthy volunteers consumed a very-low-calorie diet for 2 d to achieve a body-weight loss mainly from a loss of fat-free mass, ie, of glycogen plus water. Body weight, body density, and bioelectrical impedance were measured before and after weight loss. Body-weight loss was 1.3 +/- 0.5 kg. Loss of fat-free mass as measured by densitometry was 1.2 +/- 0.8 kg. Changes in body weight and fat-free mass measured by densitometry did not differ significantly and were significantly different from zero. Reduction of fat-free mass as determined by bioelectrical impedance was 0.5 +/- 0.8 kg, which was significantly different from body-weight loss and loss of fat-free mass as measured by densitometry but not significantly different from zero. The results show that after weight loss the bioelectrical impedance method overestimates the fat-free mass by approximately 1 kg. PMID- 2923072 TI - Measured and predicted calorie requirements of adults during recovery from severe burn trauma. AB - Major burn trauma produces large elevations in metabolic energy expenditure (MEE) during acute care. However, overfeeding can occur and is detrimental to recovery. The formulae often used to estimate caloric support to meet MEE are based on body weight, predicted resting metabolic rate (RMR), body surface area, or the total body surface area burned (BSAB). These predictive equations originate from studies of less than or equal to 30 patients generally lacking measurements beyond the third week of convalescence. We report 565 measurements by indirect calorimetry for 122 adults between the burn day and day 149 postburn. A standardized protocol of nutritional support and early wound closure was followed. Predictions of MEE are compared in subcategories of BSAB (2-25%; 30 50%; 51-75%; and 76-98%). For major burns exceeding 30% BSAB, 2X the predicted RMR was consistently closest to the measured MEE, assuring adequate calorie provision while minimizing the risk of overfeeding. PMID- 2923073 TI - Repetitive weight loss and weight regain: effects on weight reduction, resting metabolic rate, and lipolytic activity before and after exercise and/or diet treatment. AB - Body composition, maximal aerobic power (VO2 max), resting metabolic rate (RMR), and lipolytic activity of abdominal adipocytes were measured in 20 women (body mass index [BMI] = 33.5) during 14 wk of exercise training (4 h/wk at 60% of VO2 max) and dietary restriction (840 kcal/d). Frequent dieters (yo-yo) and women without a dietary history (non-yo-yo) were matched into the following groups: diet-exercise yo-yo (DE-Y), diet-exercise non-yo-yo (DE-NY), and diet-non-yo-yo group (D-NY). After 14 wk significant differences in weight loss and fat loss were revealed between D and DE groups but not between yo-yo and non-yo-yo dieters. RMR decreased in all groups but there was a significantly smaller decline after 14 wk for the diet-exercise groups. No effects of frequent dieting or exercise on basal and stimulated lipolytic activity were observed. PMID- 2923074 TI - Aspartame and its constituent amino acids: effects on prolactin, cortisol, growth hormone, insulin, and glucose in normal humans. AB - Because large doses of phenylalanine stimulate prolactin secretion in man, we studied the acute effects of oral doses of aspartame (0.534 g, equivalent to the amount of aspartame in approximately 1 L beverage), aspartic acid (0.242 g), and phenylalanine (0.3 and 1.0 g) on serum prolactin and other hormones in normal humans. Prolactin was not stimulated by any of the aspartame meals, aspartic acid, or 0.3 g phenylalanine; a small rise in serum prolactin, similar to that produced by a high-protein mixed meal, followed ingestion of 1.0 g phenylalanine. Serum growth hormone showed no statistically significant changes in response to any of the experimental meals whereas cortisol and insulin fell slightly and glucose rose slightly during each of the meals. We conclude that these doses of aspartame do not alter secretion of prolactin, cortisol, growth hormone, or insulin in normal individuals. PMID- 2923075 TI - Diet and plasma androgens in postmenopausal vegetarian and omnivorous women and postmenopausal women with breast cancer. AB - We studied 27 postmenopausal women, 9 vegetarians, 10 omnivores, and 8 apparently healthy women with breast cancer (BC), four times during 1 y. Dietary intakes were recorded and plasma androgens and sex-hormone-binding globulin (SHBG) binding capacity were determined. Androstenedione (A), testosterone (T), free T (FT), and SHBG were higher in omnivores than in vegetarians. In multiple correlation analysis, intakes of protein and fat were positively correlated with A, T, and FT, whereas the intakes of carbohydrate, grain, total fiber, and grain fiber showed the opposite correlations. Protein intake was positively correlated with percentage FT (%FT) and negatively with SHBG. BC patients had a similar pattern to omnivores with even higher levels of A and T (significant compared with vegetarians) and they showed significantly higher FT and lower SHBG than both control groups. We conclude that a Western-type diet in postmenopausal women is associated with high A, T, %FT, FT, and low SHBG and this pattern was apparent in the BC patients. PMID- 2923076 TI - Postprandial lipemia and chylomicron clearance in athletes and in sedentary men. AB - To examine the effects of exercise on postprandial serum triglyceride (TG) metabolism, we measured oral and intravenous fat tolerance and chylomicron-TG half-life in highly trained endurance athletes and in a sedentary control group matched for body weight and fasting serum TG concentration. Postprandial lipemia was lower in athletes after meals containing 40 g fat (1.5 +/- 0.7 vs 2.6 +/- 1.5 mmol.L-1.8 h-1, p less than 0.001) or 140 g fat (2.5 +/- 1.2 vs 6.1 +/- 1.9 mmol.L-1.8 h-1, p less than 0.001). The disappearance of an intravenous bolus of Intralipid was faster in athletes (5.4 +/- 1.2%/min) than in sedentary men (4.3 +/- 0.8%/min, p less than 0.01). The half-life of chylomicron-TG was shorter in athletes (3.0 +/- 0.8 min) than in sedentary men (4.0 +/- 1.0 min, p less than 0.05). These findings indicate that chronic exercise decreases postprandial lipemia by reducing chylomicron-TG's half-life. This effect is due partly to reduced fasting serum TG pool size and partly to a direct effect of exercise on the serum TG removal system. PMID- 2923077 TI - Linoleic-acid-enriched diet: long-term effects on serum lipoprotein and apolipoprotein concentrations and insulin sensitivity in noninsulin-dependent diabetic patients. AB - Long-term (30 wk) effects on serum lipoproteins and insulin sensitivity of two diets, one with a low polyunsaturated to saturated fat ratio (P:S 0.3) and one with a P:S of 1.0, were compared in 14 patients with noninsulin-dependent diabetes mellitus (NIDDM) in a crossover study. Total and LDL-cholesterol levels declined by 7.6% (p less than 0.01) and 9.8% (p less than 0.01), respectively, during the high P:S diet. VLDL-, HDL2-, and HDL3-cholesterol; triacylglycerol; and apolipoprotein A1, A2, and B levels were not affected by the change in P:S. Despite a modest increase of insulin-mediated glucose disposal at physiologic insulinemia during the high P:S diet, no influence was seen on glycemic control, and on blood glucose, plasma insulin, and C peptide responses to mixed meals. In conclusion, a linoleic-enriched diet in patients with NIDD causes a less atherogenic lipoprotein profile but does not influence glycemic control and carbohydrate tolerance. PMID- 2923078 TI - Bile-salt-activated lipase: effect on kitten growth rate. AB - Because of the presence of bile-salt-activated lipase in cat milk, the dependence of the kitten on bile-salt-activated lipase is anticipated for milk fat absorption. To test this hypothesis, we initiated a feeding experiment comparing the growth rate of kittens fed with formula with those fed with formula and supplemented with purified human milk bile-salt-activated lipase. The results indicated that the kittens fed formula with supplemental enzyme had a growth rate twice that of kittens fed with formula alone. This study also indicated that the kitten can be utilized as an animal model in the investigation of the functional role of bile-salt-activated lipase. In this study we also performed the partial characterization of cat milk protein and fat. PMID- 2923079 TI - Human milk proteins: separation of whey proteins and their analysis by polyacrylamide gel electrophoresis, fast protein liquid chromatography (FPLC) gel filtration, and anion-exchange chromatography. AB - Human milk proteins are of nutritional and physiological significance to the newborn infant. To further study these proteins, a rapid procedure to separate and analyze human milk whey proteins was developed using fast protein liquid chromatography (FPLC). First, to separate whey proteins from casein, different variables such as low- or high-speed centrifugation at different temperatures with or without adjustment of pH to 4.6 or 4.3 and with or without addition of calcium to whole milk or skim milk were tested. Each variable was evaluated by gel filtration, anion-exchange chromatography, sodium dodecyl sulphate (SDS) polyacrylamide gradient gel electrophoresis, immunoelectrophoresis, and immunodiffusion. The optimum method for a discrete separation of whey and casein is the adjustment of whole milk to pH 4.3 with addition of 60 mmol calcium/L, followed by ultracentrifugation. Rapid and sensitive separation and analysis of whey proteins was achieved by FPLC gel filtration and anion-exchange chromatography. PMID- 2923080 TI - Microcalorimetric study of muscle and platelet thermogenesis in anorexia nervosa and bulimia. AB - Muscle and platelet thermogenesis was measured by direct microcalorimetry in patients with anorexia nervosa. The median heat production, as calculated per unit of tissue mass, was 0.35 mW/g in vastus lateralis muscle, which is significantly lower (p less than 0.001), by approximately 50% than that in matched healthy subjects, 0.74 mW/g. The average deficit in body weight was 35%. Platelet heat production was decreased to a lesser degree with median values being 51.3 fW per cell and 60.9 fW per cell, respectively (p less than 0.02). Patients with bulimia without concomitant anorexia nervosa had normal heat production values. In the control group a positive correlation appeared (rs = 0.75, p less than 0.02) between resting muscle heat production and body surface area whereas no such relationship was found in the anorexic group. PMID- 2923081 TI - Gustatory function and dietary habits in users and nonusers of smokeless tobacco. AB - Nicotine and smoking may modify gustatory function or preferences and are associated with altered energy balance; however, there is no information on whether smokeless tobacco (ST) has similar effects. Evaluations of gustatory function (threshold sensitivity, perceived intensity of suprathreshold stimuli, preferences) were conducted on 28 chronic ST users and 30 nonusers after both abstaining and using ST. Subjects also maintained 7-d dietary records that included descriptions of the predominant taste qualities of foods. There were few user vs nonuser differences in gustatory measures. Among nonusers, use of ST reduced perceived intensity of salty, sour, and bitter stimuli. Users reported greater alcohol intakes and lower consumption of carbohydrates, sweet foods, fruits, and grains. Chronic use of ST does not appear to have substantial effects on gustatory function but may be associated with decreased carbohydrate intakes, perhaps related to increased alcohol use and possibly because of reduced consumption of sweet-tasting foods. PMID- 2923082 TI - Conjunctival impression cytology: feasibility of a field trial to detect subclinical vitamin A deficiency. AB - Two hundred and thirty-six Guatemalan children aged 2-14 y were examined for subclinical vitamin A deficiency by use of conjunctival impression cytology (CIC). The feasibility of the technique and quality of a modified touch procedure were assessed. Neither lid speculum nor physical restraint in the form of a papoose board was used. The CIC technique was easily performed on children aged greater than 3 y but was more difficult among those less than or equal to 3 y. Laboratory processing of specimens is uncomplicated but interpretation may be problematic and requires clearly defined criteria of normal and abnormal cytology as well as careful standardization of readers. PMID- 2923083 TI - Ascorbate and dehydroascorbate: distribution in mononuclear cells of healthy elderly people. AB - Concentrations of ascorbic acid and total ascorbate (ascorbic acid + dehydroascorbic acid) were determined in mononuclear cells from eight elderly men and nine elderly women (aged greater than 65 y) on controlled intakes of vitamin C. No increase in mononuclear cell ascorbic acid concentration was observed for intakes between 30 and 280 mg/d. A significant increase in total ascorbate concentrations was observed for the same range of intakes (p less than 0.01), primarily because of an increase in dehydroascorbic acid. Women were found to have significantly higher ascorbic acid concentrations in mononuclear cells than men (p less than 0.02) for similar intakes of vitamin C. No difference was observed for total ascorbate concentrations. The ratio of dehydroascorbate to ascorbate increased with increasing intake of vitamin C for both men and women. PMID- 2923084 TI - Preferential incorporation of alpha-tocopherol vs gamma-tocopherol in human lipoproteins. AB - Approximately 12 h after the ingestion of a single dose containing 1000 mg each of all-rac-alpha-tocopherol and RRR-gamma-tocopherol, the plasma and lipoproteins of normal subjects contained equal increases of both tocopherols; by 24 h the concentration of gamma-tocopherol, but not the alpha-tocopherol, decreased sharply. Similar studies in hyperlipidemic subjects demonstrated that the plasma and the chylomicron fraction from lipoprotein lipase-deficient patients (with elevated chylomicrons) contained both tocopherols up to 24 h, whereas plasma from a patient with dysbetalipoproteinemia (with elevated beta very-low-density lipoproteins) displayed the decrease in gamma-tocopherol at 24 h. These studies demonstrate that both alpha- and gamma-tocopherols are absorbed and secreted by the intestine in chylomicrons, and suggest that alpha-tocopherol is preferentially secreted by the liver in nascent lipoproteins. Furthermore, studies in post-gall bladder surgery patients suggest a preferential secretion of gamma-tocopherol in bile. Thus, the liver rather than the intestine appears to discriminate between alpha- and gamma-tocopherols. PMID- 2923085 TI - Calcium supplements and milk: effects on acid-base balance and on retention of calcium, magnesium, and phosphorus. AB - The effect of supplementing a basal diet containing 697 mg calcium daily (17.4 mmol/d) with an additional 900 mg Ca daily from milk, Ca chloride, or a Ca carbonate preparation was examined in eight adult males during a 56-d metabolic balance study. The ingestion of the milk or Ca supplements had no overall effect on Ca retention by these subjects because the milk and supplements depressed apparent absorption of Ca in the gut and fractional tubular reabsorption of Ca in the kidneys. Supplementation of the diet with CaCl and to a lesser extent with milk significantly increased renal acid excretion whereas supplementation with CaCO3 depressed renal acid excretion. The three Ca supplements significantly altered magnesium and phosphorus absorption and urinary excretion in different manners but had no overall effect on retention of P or Mg. The responses of our subjects to these treatments may be different than those of subjects who are chronically in negative balance in regard to Ca. PMID- 2923086 TI - Lifetime calcium intake and physical activity habits: independent and combined effects on the radial bone of healthy premenopausal Caucasian women. AB - Lifetime calcium intake and lifetime physical activity (PA) habits of 181 healthy premenopausal Caucasian women (aged 20-50) were studied. Nondominant arm was measured by single-photon absorptiometry at the distal (Dis) or 5-mm site and the midshaft (Mid) or two-thirds site of the radius. Values of bone mineral content (BMC), bone width (BW), and bone mineral density (BMD) were obtained. An intermediate or high lifetime Ca (greater than 500 mg/d) was significantly associated with a greater DisBMC (p = 0.0031), DisBMD (p = 0.0031), MidBMC (p = 0.0015), and MidBMD (p = 0.0015) when adjusted for PA. Similarly, with Ca adjusted for, a high lifetime PA (greater than or equal to 45 min of moderate to strenuous activity four times a week) was significantly associated with greater DisBMC (p = 0.0032), DisBMD (p = 0.0022), MidBMC (p = 0.0012), MidBW (p = 0.0173), and MidBMD (p = 0.0546). These findings suggest important roles for both adequate Ca intake and PA habits in enhancing peak adult skeletal mass and a trade-off between these two variables, when each was intermediate or higher. PMID- 2923087 TI - Iron absorption in humans as influenced by bovine milk proteins. AB - The effect of the two major bovine milk protein fractions on the dialyzability of iron in vitro under simulated gastrointestinal conditions and on the absorption of Fe by humans was studied. Liquid-formula meals were prepared from hydrolyzed maize starch, corn oil, and either spray-dried egg white or a milk-protein product. In meals containing egg white, 3.32% of the Fe was dialyzable. The substitution of casein and whey protein products reduced the dialyzable fraction to 0.19-0.56% and 0.86-1.60%, respectively. Percentage Fe absorption was also reduced by the substitution of casein or whey protein for egg white. Mean absorption values fell from 6.67 to 3.65% and 2.53 to 0.98%, respectively. When the intact milk-protein products were replaced by enzyme- or acid-hydrolyzed preparations, the dialyzable fraction increased markedly and in proportion to the extent of hydrolysis. A similar but much smaller effect on absorption was observed. These studies suggest that bovine casein and whey proteins are responsible at least in part for the poor bioavailability of the Fe in some infant formulas. PMID- 2923088 TI - Iron status: prevalence of impairment in three Hispanic groups in the United States. AB - Little is known about the iron status of Hispanic groups in the United States. Data from the Hispanic Health and Nutrition Examination Survey were used to estimate the prevalence of impaired Fe status for persons aged 5-74 y from three Hispanic groups: Mexican Americans (MAs), Cubans, and Puerto Ricans; prevalences were also calculated for non-Hispanic whites (NHWs) and non-Hispanic blacks (NHBs) using data from the second National Health and Nutrition Examination survey. A three-variable model called the MCV model was used to assess impaired Fe status. Prevalences based on the MCV model did not differ between Hispanic groups. Differences between Hispanics and non-Hispanics occurred only among 20-44 y-old females, where MAs had a higher prevalence than NHWs or NHBs. With this exception, these Hispanic groups do not appear to be at greater risk of impaired Fe status than non-Hispanics. PMID- 2923089 TI - Fasting plasma amino acids in elderly men. AB - The fasting amino acid profile in 22 healthy young men aged 25-35 y (group A) was compared with the fasting profile in 21 healthy independent men aged 65-85 y (group B), in 23 orally-fed nursing home men with dementia aged 65-92 y (group C), and in 17 tube-fed nursing home men with dementia aged 65-88 y (group D). Groups B, C, and D had significantly (p less than 0.05) lower levels of methionine and branched-chain amino acids than group A. Methionine was significantly lower in groups C and D than in group B. The ratio of essential to nonessential amino acids was significantly lower in groups B, C, and D than in group A. The data suggest that the intake of essential amino acids may often be suboptimal in both independent and institutionalized elderly men. PMID- 2923090 TI - Relationship of alcohol consumption to diet: a population-based study in Hawaii. AB - The relationship of alcohol use to diet was examined in 2272 male and 2337 female adults aged 45 y and older who provided a quantitative diet history during 1977 1979. Mean values for each dietary variable, adjusted for smoking, ethnicity, income, and education, were compared in each sex between abstainers and drinkers and by tertile of ethanol intake. Linear relationships with extent of drinking were also sought. Drinkers were found to be less obese than abstainers. Consumption of carbohydrate, vitamins, calcium, fruits, fruit juices, and raw vegetables was greater among abstainers whereas consumption of fat (particularly polyunsaturated fatty acids), cholesterol, zinc, meat, pickled vegetables, and dried fish was greater among drinkers. Because validations of dietary questionnaires have shown that alcohol consumption is more accurately recalled than food intake, the possibility of a residual confounding effect for these dietary variables should be considered in epidemiologic studies of alcohol and health. PMID- 2923091 TI - The value of morphometry and DNA flow cytometry in addition to classic prognosticators in superficial urinary bladder carcinoma. AB - In 80 patients with primary superficial bladder carcinoma Tumor Nodes Metastasis (TNM classification: stages Ta and T1) with adequate follow-up of at least four years, the value of selective nuclear morphometry and DNA flow cytometry on paraffin-embedded material in addition to classic prognosticators was assessed. Only the quantitative techniques appeared to be valuable predictors of new tumor occurrence. The recurrence rate in patients with large nuclei (mean nuclear area greater than 95 micron 2; n = 29) and in aneuploid cases (n = 30) was significantly higher (Wilcoxon: P = 0.05 and P = 0.0001) than in those with small nuclei (mean nuclear area less than = 95 micron 2; n = 51) and diploid cases (n = 50). The prevalence of large nuclei and aneuploidy also appeared useful to predict progressive recurrence, i.e., grade 3 or/and muscle invasive carcinoma (TNM classification: stages T2-T4) (chi-square: P less than 0.0001). Clinical follow-up showed that only 62.1% of the cases with large nuclei remained free of progressive recurrence, compared with 92.2% of those with small nuclei (Mantel Cox: P less than 0.0001). For the aneuploid and diploid cases, these figures came to 53.3% and 98% (Mantel-Cox: P less than 0.0001). By multivariate analysis DNA ploidy was selected as the best discriminator. None of the classic prognosticators, including histologic grade, had additional prognostic value. Also, morphometry did not add to the prognosis prediction, which can be explained by the considerable overlapping between the prevalence of large nuclei and aneuploidy (24 of 29 and 30 cases, respectively). These findings practically suggest that patients presenting with superficial carcinoma with large nuclei (mean nuclear area greater than 95 microns 2) or aneuploid DNA values should be treated more aggressively. PMID- 2923092 TI - Expression of type 1 and type 2 blood group-related antigens in normal and neoplastic gastric mucosa. AB - The distribution of the blood group-related antigens type 1 (Lewis(a) [Le(a)], Lewis(b) [Le(b)]) and type 2 (H type 2, Y) has been examined in histologically normal and malignant mucosa of 40 surgical specimens of patients with adenocarcinoma of the stomach, with the use of a panel of monoclonal antibodies. Patients' Lewis phenotype and secretor status are correlated to the authors' findings. The surface epithelium of normal pyloric and fundic mucosa expressed the Lewis isoantigen (Le(a) in Le[a+b-] phenotype and Le(b) in Le[a-b+] phenotype), whereas the deep areas of this mucosa no showed the Le(a), Le(b) antigens and expressed the Y and H type 2 antigens whatever the secretor status of patients. Nineteen of 24 patients with Le(a-b+) phenotype showed anomalous expression of Lea antigen in neoplastic cells. In three of them, this alteration was found in tumor adjacent mucosa. No expression of Le(a) or Le(b) antigens was found in tumors or normal mucosa from Le(a-b-) phenotype patients. PMID- 2923093 TI - Blast-like cells in cerebrospinal fluid of neonates. Possible germinal matrix origin. AB - Primitive cell clusters (PCCs) composed of immature blast-like cells were observed in Wright's-stained cerebrospinal fluid (CSF) cytocentrifuge specimens from four infants over an 18-month period. All of these patients had hydrocephalus; in three this was secondary to subependymal germinal matrix intraventricular hemorrhage (IVH) associated with prematurity. The fourth was associated with Arnold-Chiari malformation, Chiari type II. In the CSF samples from the patients with IVH, hemosiderin-laden macrophages were also prominent and, in some cases, were intimately admixed with the PCCs. Immunoperoxidase staining of cytocentrifuge preparations from one of the patients revealed that the PCCs stained with neuron-specific enolase (NSE) but not with pan-leukocyte antibodies. Cells with similar morphologic characteristics to PCCs in the CSF of infants have been infrequently illustrated in the literature and thought to be of hematopoietic origin. However, the immunohistochemical findings and the clinical presentation suggest that PCCs are most likely germinal matrix cells. PMID- 2923094 TI - Crohn's disease uveitis. Parasitization of vitreous leukocytes by mollicute-like organisms. AB - Crohn's disease (CD) is an idiopathic chronic inflammatory gut disease with frequent extragut inflammatory manifestations in the eyes, orbit, lungs, joints, and skin. A bacterial cause of CD is suspected, but cultivation of a specific pathogen has not been forthcoming. Mollicute-like organisms (MLOs) were recently reported to cause human chronic ocular inflammatory disease. Inoculation of this MLO into mouse eyelids produced chronic progressive granulomatous ocular and orbital inflammatory disease. In addition, MLOs disseminated to produce similar disease in the gut, heart, and lungs. MLOs are noncultivable cell wall-deficient bacterial pathogens. Because they also pass bacteria-retaining 0.450-micron filters, they can be overlooked or confused with viruses. Because MLOs have a characteristic ultrastructural appearance, they can be identified in diseased cells with the use of a transmission electron microscope. MLOs parasitize and destroy leukocytes. They alter the nucleus, replace the cytoplasm, and destroy organelles. MLO-caused disease is treatable by certain antibiotics. This report describes MLO-parasitized vitreous lymphocytes, monocytes, and polymorphonuclear leukocytes from three patients with CD who had chronic uveitis. The results indicate that MLOs probably caused the uveitis of these patients with CD. The gut as the possible source of the MLO is suggested. Rifampin therapy of Crohn's and MLO-caused disease is discussed. PMID- 2923095 TI - Hepatic sinusoidal fibrosis in agnogenic myeloid metaplasia. AB - Autopsy studies in two patients who had agnogenic myeloid metaplasia of long duration revealed significant extramedullary hematopoiesis in the liver associated with significant hepatic perisinusoidal/sinusoidal fibrosis. Fibrosis was nonzonal and irregularly distributed throughout the livers. Early changes were found in areas with normal parenchymal architecture and showed significant thickening of collagen fibers surrounding the liver cell plates. In areas with extensive fibrosis, coarse collagen fibers filled the sinusoidal space and resulted in the loss of hepatocytes, but nodular regeneration was absent. Hepatic perisinusoidal/sinusoidal fibrosis in livers with extensive extramedullary hematopoiesis may be more common than previously recognized. PMID- 2923096 TI - Evaluation of stat and routine turnaround times as a component of laboratory quality. AB - Quality assurance has been an essential part of clinical laboratory operations for more than two decades. Analytic precision and accuracy goals have been established, and laboratory performance is monitored periodically. For a laboratory test to be useful, it must be available in a timely manner. Expedience of result reporting has not, however, been routinely included among measures of laboratory quality. The authors evaluated stat and routine turnaround times for 42,414 requests on 24 clinical analytes over a 14-day period with the use of a personal computer. Median turnaround time is 1.70 times faster for stat than for routine tests. When examined by shift, average turnaround time is considerably faster for tests ordered stat than for tests ordered routinely during the day and evening shifts, when the work load is the greatest. The authors are now examining turnaround time as an indicator of quality laboratory performance and efficiency. Computer systems in many clinical laboratories already have the sophistication necessary to perform turnaround time analysis. The authors recommend that clinical laboratories begin to include timeliness of stat and routine result reporting as part of their quality assurance programs. Laboratories may also wish to investigate the usefulness of stat requests during slower shifts because these requests may interrupt the normal flow of specimens without expediting result reporting. PMID- 2923097 TI - Special report: perils, problems, and minimum requirements in shipping pathology slides. PMID- 2923098 TI - An American Board of Orthodontics case report. Surgical treatment of adult Class II, division 2 malocclusion. AB - A case report is presented of an adult Class II, Division 2 malocclusion with a deep bite, excessive overjet, mandibular deficiency, and accentuated curve of Spee. Treatment consisted of full-banded orthodontic appliances combined with a surgical mandibular advancement using a midsagittal split osteotomy. PMID- 2923099 TI - An American Board of Orthodontics case report. Correction of a severe Class II malocclusion. AB - Many factors often combine to create a malocclusion. Broadly these include the genetic potential of the individual and environmental or local factors. Class II, Division 1 malocclusions may result from both inherited skeletal and dental patterns and an additional environmental factor such as thumb sucking or some other habit. Successful treatment of patients with this type of malocclusion requires both an orthodontic correction of the existing dental and skeletal problems and also control of any deleterious habit. The following case report deals with a patient who had such a malocclusion. PMID- 2923100 TI - Biomechanical effect of anteriorly directed extraoral forces on the craniofacial complex: a study using the finite element method. AB - This study was designed to investigate the biomechanical effect of protractive maxillary orthopedic forces on the craniofacial complex by use of the three dimensional finite element method (FEM). The three-dimensional FEM model was developed on the basis of a dry skull of a young human being. The model consisted of 2918 nodes and 1776 solid elements. Eighteen cranial and facial sutural systems were integrated in the model. An anteriorly directed 1.0-kg force was applied on the buccal surfaces of the maxillary first molars in both a horizontal parallel direction and a 30 degree obliquely downward direction to the functional occlusal plane. The nasomaxillary complex showed a forward displacement with upward and forward rotation in a horizontal protraction case, whereas a downward force produced almost translatory repositioning of the complex in an anterior direction. High stress levels were observed in the nasomaxillary complex and its surrounding structures. However, the pattern of stress distributions within the complex was different in two force systems. A downward protraction force produced relatively uniform stress distributions, indicating the importance of the force direction in determining the stress distributions from various orthopedic forces. PMID- 2923101 TI - Labial root torque: effect on the maxilla and incisor root apex. AB - This study was designed to determine the effectiveness of labial root torque on anterior nasomaxillary development. Quantification was made of the angular and linear changes in Downs' point A (representing midsagittal basal bone) and incisor point A (representing the dentoalveolar bone) and any concomitant incisor root resorption. The study was divided into two parts: part 1--to determine the anatomic configuration of the premaxillary region by use of laminagraphy on skulls, and part 2--to use the morphologic landmarks found in part 1 to assess the development of the nasomaxillary complex in maxillary retrusive patients. The clinical study involved 17 maxillary retrusive patients, aged 8.0 to 15.7 years, who had been treated for a period between 0.31 and 3.70 years with edgewise advancing mechanics. Clinical results indicate that during the first phase of orthodontic treatment with labial root torque, encompassing a 0.63-year mean treatment period, a greater rate of advancement of Downs' point A was produced when compared with normal growth. The skeletal convexity increased, whereas normal growth straightened the profile. Incisor point A advanced at a greater rate than Downs' point A, suggesting that treatment caused a larger dentoalveolar effect than the effect on midsagittal basal bone. When treatment was extended to 1.57 years, similar changes were found but at a reduced rate. Overall apical root resorption was 12.7%/year. Sex and age were not found to have any correlation to the amount of apical root loss. PMID- 2923102 TI - Changes in facial profile during orthodontic treatment with extraction of four first premolars. AB - Soft-tissue profiles were examined in 160 orthodontic patients treated with removal of four first premolars. Records of 10- to 30-year-old patients were selected at random from five sources: patients treated by Charles H. Tweed on file at the Tweed Foundation, patients treated with the Begg technique by the Kesling-Rocke group, patients from two practices with pretorqued, preangulated edgewise appliances, and patients with premolars enucleated at an early age. The mean changes for the total sample included an increase of 5.2 degrees in the nasolabial angle, and retraction of the upper and lower lips 3.4 and 3.6 mm to the E line, respectively. For different measurements, between 5% and 25% of the sample had values indicating more protrusive lips after treatment. In comparisons among groups, the Tweed patients generally exhibited the greatest lower lip retraction. When profile changes were compared to values representing normal (or "ideal") facial esthetics, it was evident that extraction of four first premolars generally did not result in a "dished-in" profile. Approximately 10% to 15% of cases could be defined as excessively flat after treatment. Eighty percent to 90% of patients treated by extraction of four first premolars had soft-tissue measurements that suggested the profile was improved by treatment or remained satisfactory throughout treatment. PMID- 2923103 TI - Comparison of the dentofacial patterns for native Greek and American-Caucasian adolescents. AB - The study of the craniofacial relations and variations in man has long been used to differentiate various racial groups in physical anthropology. Morphologic features of different races and ethnic groups are not randomly distributed but appear in geographic clusters. Richardson wonders whether there is only one race, comprising ethnic groups separated by cultural, climatic, and geographic boundaries, causing subtle changes in facial morphology. Since the introduction of roentgenographic cephalometry in orthodontics, several methods of analysis have been developed for clinical diagnosis and treatment planning. Also, these methods have been used to establish the cephalometric norms of different ethnic groups: American Negro, Australian aborigine, American Mexican, Norwegian, Indian, Japanese, Swedish, and Iranian. Sassouni, Ricketts, and others have concluded that norms differ between Caucasians and other ethnic and racial groups. Ethnic differences in facial traits do exist. Awareness of the normal dentofacial pattern of each ethnic group will undoubtedly ensure better success of treatment to establish optimal facial harmony. These conclusions prompted the present investigation, which compares Greek and American-Caucasian dentofacial patterns of adolescents, and provides information on the facial characteristics of Greek adolescents. To date, no similar study has been made. PMID- 2923104 TI - In re: "The specialty of orthodontics". PMID- 2923105 TI - Remarks of the AAO president at the opening ceremony of the 2nd International Congress of the Japan Orthodontic Society, Oct. 18, 1988. PMID- 2923106 TI - Legal aspects of orthodontic practice: risk management concepts. Diagnosis, root resorption, and progress monitoring. AB - In this and succeeding issues of the American Journal of Orthodontics and Dentofacial Orthopedics, factual risk management scenarios will be presented. These scenarios are based on composites of actual court cases that have been tried to verdict or decision. Valuable risk management lessons may be learned from careful analysis of the course of the events described. Please be advised that the standard of care determined in any case is specific for that jurisdiction and that set of facts as established by expert testimony for the prevailing party. PMID- 2923107 TI - Inpatient treatment of PCP abusers and users. AB - Screening of 155 consecutive admissions to a voluntary, 4-6 week substance abuse inpatient rehabilitation program revealed a 13% prevalence of PCP abuse (defined by DSM-III criteria) and a 23% prevalence of nonabusive PCP use. The 20 PCP abusers were significantly younger (31.6 vs 40.2 years) and had more prior arrests (2.0 vs 0.8) than the 36 nonabusive users, but did not differ in other sociodemographic characteristics. The age range of patients was older than previously reported in the literature, with three PCP abusers (15%) and 15 users (42%) 40 years of age or older. A majority of both abusers (80%) and users (97%) also abused other drugs, including alcohol (57%), opiates (29%), marijuana (29%), and stimulants (18%). The mean length of stay for PCP abusers was 27 days, with 11 completing inpatient treatment. Urine samples were collected upon admission from all patients and assayed for PCP by gas chromatography with N-P detection (sensitivity = 0.1 ng/mL). Patients with initial positive PCP results had follow up urines collected at least weekly until the PCP assay was negative or they left the treatment program. Twenty-seven percent of patients had PCP detected in admission urine samples, one-third of whom initially denied PCP use. Six patients still had PCP detected after 4 weeks of hospitalization, without evidence of PCP reuse. These findings suggest that PCP abuse and use are common among unselected patients seeking substance abuse inpatient treatment and that they are not confined to the adolescent/young adult age group. PMID- 2923108 TI - Psychoactive drugs, alcohol, and stress and coping processes in older adults. AB - Data are presented on a) the relationship between psychoactive substance use and personal characteristics, b) the relationship between psychoactive substance use and appraisal of and coping with stressful situations, and c) the use of psychoactive substances specifically to cope with stress among older people. Data were provided by 141 65-to-74-year-old retired Caucasians who were assessed repeatedly over 6 months. Compared to national samples, subjects were relatively heavy users of alcohol and average users of psychoactive drugs. Use of alcohol increased with income, and drug use was associated with several psychosocial characteristics as well as with psychological and somatic health. Psychoactive substance use did not relate to the ways subjects appraised and coped with stressful encounters. Further, only a small number of subjects used drugs or alcohol specifically to help them cope in these encounters. The findings about psychoactive drug users are compared with other findings about misusers of drugs, and the risks associated with each type of drug use are discussed. PMID- 2923109 TI - What happens to babies exposed to phencyclidine (PCP) in utero? AB - Fifty-seven infants exposed to phencyclidine (PCP) in utero were followed for the first year of life. Thirty-six (65%) of the 55 for whom birth records were available manifested symptoms of neonatal narcotic withdrawal syndrome, including 16 (52%) of those whose mothers denied opiate abuse during pregnancy. Temperament problems were noted in 47% of the babies and sleep problems in 14%. The majority of infants grew normally, but a larger than expected number started out small and remained small. Testing using the Bayley Scales of Infant Development at age one year revealed a mental development index (mean +/- SD) of 94 +/- 10 and a psychomotor development index of 98 +/- 10. Attachment behavior was abnormal in 17%. Most infants were cared for by their natural mother. Further studies are needed to determine later effects of in utero PCP exposure, as well as effects on the infants being raised by women who have used PCP. Phencyclidine toxicity needs to be considered when evaluating babies with signs of neonatal narcotic withdrawal syndrome. PMID- 2923110 TI - The allocation of drug addicts to different types of treatment. An evaluation and a two-year follow-up. AB - In Denmark the official aim has been to reduce methadone treatment, even though no effort is made to directly forbid this therapy. A multiprofessional committee was established to regulate and limit methadone treatment. There were no specific guidelines for what type of drug addict should be treated with methadone. We found that allocation for the Regional Narcotic Committee of the Municipality of Copenhagen during 1982-1984 did not serve the desires of the addicts because only 41% followed it. Allocation also did not follow the principles of research in this field. In a 2-year follow-up investigation we found that drug addicts had a mortality rate of 6.3/year, rising criminality (significant), and falling availability to the labor market (nonsignificant). We therefore came to the conclusion that the efforts of the committee did not improve the conditions of drug addicts. Only those drug addicts who had been under almost constant methadone treatment had a low lethality and a falling number of criminal convictions (significant). Finally, it is concluded that limited research within this field prevents more specific treatment and improved use of financial resources. PMID- 2923111 TI - The natural history of alcoholism versus treatment effectiveness: methodological problems. AB - A majority study of alcoholism treatment concluded that results of treatment were no better than the natural history of untreated alcoholism. This conclusion cannot be considered valid because of methodological problems which render the treated and untreated samples incomparable. The latter methodological problems include age cohort differences between the untreated and treated samples, and differences in socioeconomic status. Other issues confounding the original conclusion are inadequacy of the minimal treatment provided. Major reviews of alcoholism treatment and recent outcome studies indicate that treatment optimism is warranted in contrast to the view that treatment renders no advantage over "natural" outcome. PMID- 2923112 TI - The role of female occupation in severity of alcohol-related problems. AB - This study investigated whether occupational class is related to the severity of problems associated with alcohol abuse in females. Sixty-six female alcoholic inpatients at a private psychiatric hospital were studied. Of these women, 31 were workers (working at the time of admission), 18 were unemployed workers (unemployed at admission but had worked most of their adult lives), and the remaining 17 were homemakers. Problem severity was assessed for 66 alcoholic women using the Addiction Severity Index (ASI), a standardized clinical interview. A questionnaire assessing the degree of occupational stress experienced was also administered. Employment problem severity ratings from the ASI differed significantly across the three occupation subgroups [F(2,63) = 10.99, p less than .05]; the unemployed workers reported more severe employment problems than did either the workers [t(63) = 3.07, p less than .05] or homemakers [t(63) = 4.77, p less than .05]. There were no significant differences between the three groups on the other five ASI dimensions. A cluster analysis on ASI severity ratings revealed a trend for workers to have family and psychological problems in addition to alcoholism. This seems not to have had an impact on wanting a job change; significantly more homemakers (z = 4.77, p less than .05) and unemployed workers (z = 4.56, p less than .05) than workers wanted a job change. PMID- 2923113 TI - Alcoholism and family interaction: an experimental paradigm. AB - The purpose of this paper is to describe the authors' ongoing investigation of alcoholism and family interaction--a large-scale observation study involving intact families assessed under a broad range of conditions. The methodology is characterized by the inclusion of two control groups, laboratory observations involving experimental drinking procedures, and naturalistic home observations focused on dinnertime interactions. Key issues addressed involve the impact of alcoholism on the process and structure of family life, the degree to which varying patterns of family interaction serve to potentiate or inhibit the development of alcoholism in children of alcoholics, and the degree to which observed patterns vary in relation to nature of dysfunction (alcoholism versus depression). The current status and initial outcomes of the project are described in detail. PMID- 2923114 TI - The outbreeding of alcoholism. AB - A hypothesis on the outbreeding of alcoholism is presented. Supporting evidence includes historical and biologic factors as well as the inverse relationship between the length of exposure to alcohol and the prevalence of alcoholism in societies. PMID- 2923115 TI - Exposure to television as a risk factor for violence. PMID- 2923116 TI - Trends in the incidence of myocardial infarction in Western Australia between 1971 and 1982. AB - Trends in the incidence of and mortality from myocardial infarction in Perth, Western Australia, were studied for the period 1971 to 1982. The estimated age adjusted incidence rate of myocardial infarction fell by 24% in males and 37% in females over this period. The rate fell in each of six age-sex groups, but the proportional decrease in those aged less than 45 years was nearly double that in those aged 45 years and over, as it was in females compared with males and in fatal cases compared with nonfatal cases. Over 80% of the decline in mortality was in deaths outside hospital. This and seven other comparable studies all showed a net decrease in the estimated incidence of myocardial infarction in both sexes, with median annual decreases of 2% in males and 3% in females. It is concluded that the decline in the incidence of myocardial infarction contributed substantially to the observed decrease in ischemic heart disease mortality, and that the most plausible explanation for the decline in incidence is a reduction in the prevalence of risk factors for myocardial infarction. PMID- 2923117 TI - Rose Questionnaire angina among United States black, white, and Mexican-American women and men. Prevalence and correlates from The Second National and Hispanic Health and Nutrition Examination Surveys. AB - The prevalence of Rose Questionnaire angina and its association with coronary heart disease risk factors and manifestations were investigated in representative samples of the US population. The study populations included 1,135 black and 8,323 white subjects aged 25-74 years examined in the Second National Health and Nutrition Examination Survey, 1976-1980, and 2,775 Mexican-American subjects aged 25-74 years examined in the Hispanic Health and Nutrition Examination Survey, Mexican-American portion, 1982-1983. Age-adjusted prevalence rates of Rose angina were similar among black, white, and Mexican-American women (6.8%, 6.3%, and 5.4%, respectively). An excess in the prevalence of Rose angina was observed in women compared with men for white and Mexican-American persons under age 55 years, but not for those over age 55. Electrocardiographic evidence of myocardial infarction and self-reported heart attack were strongly associated with prevalent Rose angina among white men and women aged 55 years and over, but not among those below age 55. Serum cholesterol, body mass index (weight (kg)/height (m)2), current cigarette smoking, and dyspnea were independently associated with an increased risk of prevalent angina in multivariate logistic models for white women, excluding those with a prior heart attack. Because many younger women with chest pain who may consult physicians are likely to have elevations in cardiovascular risk factors, their self-reported chest pain can be used as an opportunity to intervene and reduce their future risk of cardiovascular disease. PMID- 2923118 TI - Tar content of cigarettes in relation to lung cancer. AB - Although it is generally considered established that the risk of lung cancer is directly related to the tar content of cigarettes, an examination of the results of previous studies does not yield conclusive evidence in favor of the hypothesis. The authors evaluated this issue in a study of 881 cases of lung cancer and 2,570 hospital controls who were 40 to 69 years of age; data were collected by interview in hospitals in the United States and Canada from November 1981 to June 1986. For each year of smoking, cigarette brands were classified according to their tar content as published in regular Federal Trade Commission reports (from 1967 to 1985) or the Reader's Digest (from 1957 to 1966). Tar values for years for which there was no published information were estimated by interpolation. Smokers were divided, according to the tar content of their cigarette brands averaged over a specified period, into low (less than 22 mg/cigarette), medium (22-28 mg/cigarette), and high (greater than or equal to 29 mg/cigarette) tar smokers. When the average tar content was based on cigarettes smoked at least 10 years previously, the relative risk estimates for medium and high tar smokers compared with low tar smokers were 3.0 and 4.0 after control for potentially confounding factors, including the number of cigarettes smoked per day. The trend was significant (p = 0.002). The tendency for the risk of lung cancer to increase with increasing tar content was consistent among men and women. The results provide further support for the hypothesis that the tar content of cigarettes is directly related to lung cancer risk. However, the data were limited in that there were very few subjects whose lifetime tar exposure averaged less than 10 mg/cigarette. PMID- 2923119 TI - Cancer risk after evaluation for infertility. AB - To evaluate cancer risk by various causes of infertility, the authors conducted a retrospective cohort study among 2,335 women evaluated for infertility at the Mayo Clinic between 1935 and 1964. Most cancers occurred at expected frequencies, with the exception of cancers of the thyroid (standardized incidence ratio (SIR) = 2.6) and other endocrine glands (SIR = 6.7), although analyses were based on small numbers. Patients with progesterone deficiencies (31 per cent of the study subjects) had a 20 per cent higher cancer risk than did those with other causes of infertility, with excesses deriving primarily from cancers of the lung, cervix, ovary, and thyroid and from melanoma. Breast cancer risk, however, was not elevated in either patients with progesterone deficiencies (SIR = 0.9) or patients with other causes of infertility (SIR = 1.0). Examination of other parameters of infertility, including age at evaluation, type of infertility (primary vs. secondary), and years of attempted conception, showed no elevated risks of breast cancer in any subgroup. These results fail to support previous studies that have linked progesterone deficiencies among infertile women to elevated breast cancer risk. However, the data suggest a possible involvement of a progesterone deficiency in the etiology of other cancers, particularly thyroid cancer and melanoma. PMID- 2923120 TI - Clustering of premature mortality in 1,761 insulin-dependent diabetics and their family members. AB - The clustering of premature mortality was investigated in 1,761 insulin-dependent diabetics and their family members from the Children's Hospital of Pittsburgh Insulin-Dependent Diabetes Mellitus Registry from 1950-1981. At follow-up, 5% of the mothers and 13% of the fathers were deceased. Life table analyses revealed that fathers of deceased diabetics were significantly more likely to die prematurely than fathers of living diabetics (18% vs. 8% at age 55 years; p = 0.02). A father-diabetic son concordance of mortality appeared to be responsible for this effect. A similar overall trend was observed for maternal mortality, although the difference was not statistically significant. Cause-specific analyses revealed that the increased paternal mortality was primarily the result of cardiovascular disease. Overall mortality rates of parents of deceased diabetics were higher than those of the general population, reaching statistical significance in the age group 35-44 years (p less than 0.05). Mortality among diabetic siblings was also examined. Diabetic siblings of deceased diabetics had a markedly increased risk of dying compared with diabetic siblings of living diabetics (p = 0.001). These findings indicate that premature mortality among both diabetic and nondiabetic relatives of diabetics clusters in families in which there is a deceased insulin-dependent diabetic, and suggest that the marked increase in mortality among persons with insulin-dependent diabetes may be partly under familial control. PMID- 2923121 TI - Blood lead-blood pressure relations: alcohol intake and hemoglobin as confounders. AB - A cohort of 1,052 persons (504 men and 548 women) born in 1936 and residing in the Glostrup area, Denmark, underwent a comprehensive physical examination in 1976 at age 40 years, and 966 underwent a complete reexamination five years later. The examinations included blood lead concentration and blood pressure assessment under careful quality control. Complete blood lead and blood pressure data were available for 861 of these subjects (451 men and 410 women). The median blood lead levels were 13 and 9 micrograms/100 ml at age 40 years and 9 and 6 micrograms/100 ml at age 45 years in men and women, respectively. A slightly increased blood lead concentration was seen at age 40 years in women with a systolic blood pressure above 140 mmHg and/or a diastolic blood pressure above 90 mmHg. Systolic blood pressure in men and women and diastolic blood pressure in women correlated significantly with log blood lead at age 40 years but not at age 45 years, a doubling in blood lead being associated with an increase in blood pressure of 3 mmHg or less. Of nine potential confounders assessed, only blood hemoglobin and alleged alcohol intake were significantly associated with both blood lead and blood pressure. If one or both confounders were entered into a multiple regression analysis, all associations between blood lead and blood pressure became nonsignificant, in some cases with a negative regression coefficient. In addition, the blood lead:hemoglobin ratio was poorly associated with blood pressure, particularly in individuals with a low alcohol intake. Because both hemoglobin level and alcohol intake appear to be biologically plausible confounders, any independent effect of low-level lead exposure on blood pressure could not be determined. PMID- 2923122 TI - Effect of a malaria suppression program on the incidence of African Burkitt's lymphoma. AB - From 1977 to 1982, the authors attempted a malaria suppression trial in North Mara District, Tanzania, to see whether the incidence of Burkitt's lymphoma (BL) could be lowered by reducing the level of malarial infection in a child population below 10 years of age. Immediately after initiation of the suppression trial, the prevalence of malaria fell drastically in the Mara children; however, soon after, the rate of malarial infection rose again in the trial area in spite of continued chloroquine distribution, and by 1981 the prevalence of malarial infection again reached the high levels that had prevailed in the North Mara lowlands before 1977. However, during the period of chloroquine distribution in North Mara, the level of malarial infection there was constantly lower than that observed in a comparison area in South Mara, although the two areas had been similar with respect to malaria endemicity prior to the intervention. During the years of chloroquine distribution in North Mara, the incidence rate of BL there fell considerably, from about 4 per 100,000 population to about 1 per 100,000 population, and it rose again to pretrial levels in 1984, that is, about two years after the chloroquine distribution had been terminated. This apparent association between malaria suppression and decline in BL incidence at first seemed to indicate that malaria is a causal factor in BL production. A close scrutiny of the survey data revealed, however, that the decline in BL incidence might have started several years before the chloroquine distribution began; thus it appears that the malaria suppression could not have been the sole cause of the BL decline. PMID- 2923123 TI - Epidemiologic surveillance for endemic Giardia lamblia infection in Vermont. The roles of waterborne and person-to-person transmission. AB - The authors studied 1,211 laboratory-confirmed, non-outbreak-related cases of giardiasis in Vermont residents reported through Vermont's laboratory-based active surveillance system between 1983 and 1986. Giardiasis was the most common reportable disease in the state, with an average annual incidence rate of 45.9 cases per 100,000 population per year. This rate is higher than that in other states reporting giardiasis incidence. Morbidity from giardiasis was also significant in that 30% of cases reported symptoms lasting four or more weeks. Waterborne transmission was suggested to be an important cause of non-outbreak related cases because rates of infection were highest in persons receiving nonfiltered municipal or nonmunicipal residential drinking water. Rates were also higher at higher elevations, where water supplies may be difficult to protect from contamination. In addition, the pattern of age-specific incidence rates and the high estimated incidence of infection in children attending day care suggested that person-to-person transmission also played a role in causing non outbreak-related cases. Routine surveillance data can serve to indicate likely important routes of transmission of giardiasis in the community. PMID- 2923124 TI - Longitudinal studies of infectious diseases and physical growth of infants in Huascar, an underprivileged peri-urban community in Lima, Peru. AB - Longitudinal studies of morbidity from infectious diseases and physical growth were completed from July 1982-June 1984 for 153 Peruvian newborns during the first year of life. Admission to the cohort was restricted to infants with birth weights greater than 2,500 g. Surveillance workers inquired about symptoms of diarrheal, respiratory, and other illnesses during thrice-weekly home visits; anthropometrists measured weight and length each month to assess the infants' patterns of physical growth and relative nutritional status. During 48,209 child days of observation, upper respiratory infections were present on 13,409 child days (27.8% prevalence) and diarrhea on 7,466 child-days (15.5% prevalence). The diarrhea incidence rate averaged 9.8 episodes per child-year of observation; all children had at least one episode of diarrhea. Average weights approximated those of the National Center for Health Statistics reference population during the first five to six months, but declined thereafter in relation to reference data. Average lengths were less than the reference data at all ages. The average weights for age and lengths for age of girls were generally greater than those of boys relative to the reference population. Rates of stunting and wasting increased progressively during the first year of life. PMID- 2923125 TI - Sibship size as a risk factor for hepatitis A infection. AB - Marked ethnic differences in the prevalence of anti-hepatitis A antibodies among Jews in Israel are only partly explained by variation in socioeconomic status. In this study, various sociodemographic variables were examined as possible correlates of anti-hepatitis A antibodies in a group of 552 Jewish males aged 25 44 years examined between January and April 1987. Among subjects aged 25-29 years, 41.5% of those of European and American origin had antibodies as compared with 88.5% of those of Asian and North African origin (p less than 0.0001), whereas by the age of 40-44 years, this difference had largely disappeared. In further univariate analysis, number of siblings, years of education, and number of children were also significantly associated with the presence of antibodies. When multiple logistic regression was used to control simultaneously for the effects of the other variables, sibship size emerged as the strongest correlate of anti-hepatitis A antibodies (p less than 0.0001), and it appears to explain a large part of the ethnic differences in antibody status. These findings provide strong evidence for the role of siblings in the spread of hepatitis A infection. PMID- 2923126 TI - Gestational vaginal bleeding and pregnancy outcome. AB - The relation between vaginal bleeding and pregnancy outcome was examined in a prospective study of 3,531 women seeking prenatal care in New York City from 1975 through 1985. Women were interviewed in the second trimester or later and were followed up at delivery. The frequency of vaginal bleeding during pregnancy was 22%. Few maternal characteristics or exposures were predictive of bleeding, and those that were associated with an increased risk of bleeding were only marginally so. Risk factors included advanced maternal age, previous spontaneous or induced abortion, working during pregnancy, and certain gynecologic conditions (fibroids, cervical inflammation, and ovarian cysts). Severity of bleeding was examined in relation to birth weight and length of gestation at delivery. Light bleeding during pregnancy was not associated with decreased birth weight or with shortened gestation at delivery. Heavy bleeding was associated with a decrease in mean birth weight of about 100 g (p less than 0.05) but was not significantly associated with the risk of low birth weight (odds ratio (OR) = 1.7, 95% confidence interval (CI) 0.9-3.3). Heavy bleeding was associated with preterm delivery among private patients (OR = 6.4, 95% Cl 1.7-23.5) but not public patients (OR = 0.3, 95% Cl 0.1-1.4). First trimester bleeding of any severity was marginally associated with congenital malformations in the offspring (OR = 1.7, 95% Cl 1.0-2.9); the effect was the same for major and minor abnormalities. There was no association between first trimester bleeding and placental complications of pregnancy or the delivery of a stillborn infant. PMID- 2923127 TI - Mortality in a northeastern Native American cohort, 1955-1984. AB - Patterns of mortality among members of the Seneca Nation of Indians between January 1, 1955, and December 31, 1984, were investigated. The study cohort consisted of all members of the Seneca Nation residing in New York State who were listed in the tribal rolls as of January 1, 1955 (n = 3,262). Deaths among cohort members were identified through a computer match against New York State vital records files. Sex-specific standardized mortality ratios (SMRs) were calculated on the basis of mortality patterns exhibited by the general population of New York State, exclusive of New York City. Seneca Nation males demonstrated an excess of deaths from all causes (SMR = 124), while all-cause mortality among Seneca Nation females did not differ from that expected (SMR = 106). Both males and females exhibited excess mortality from infectious diseases, diabetes mellitus, cirrhosis of the liver, and accidents and injuries. Excess mortality was also noted among males for deaths due to atherosclerosis and hernia/intestinal obstruction and among females for deaths due to pneumonia, chronic nephritis, and homicide. Both sexes exhibited a deficit of deaths due to malignant neoplasms and circulatory diseases. Findings from this study will be useful to those responsible for the planning and implementation of health care programs among the Seneca Nation of Indians and other Native American groups. PMID- 2923128 TI - Genotypic and phenotypic similarities in pulmonary function among family members of adult monozygotic and dizygotic twins. AB - Population studies have demonstrated that obstructive airways disease aggregates within families. The authors used a twin family model of analysis to estimate the genetic and environmental influences on pulmonary function. A total of 1,635 members of 414 families of adult twins (252 monozygotic, 162 dizygotic) enrolled in the Greater Boston Twin Registry were studied between 1981 and 1982. Correlations in levels of forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), adjusted for age, sex, height, and current smoking status, were compared among 16 groups of relatives sharing various degrees of genetic relatedness. A direct relation between shared genotype and the magnitude of the familial correlations for pulmonary function was observed. For FEV1, the correlations were 0.71 for monozygotic twins (100% shared genotype), 0.16 to 0.29 for relatives with 50% shared genotype, 0.09 to 0.27 for relatives with 25% shared genotype, 0.06 for cousins with 12.5% shared genotype, and -0.14 to 0.14 for unrelated family members. Correlations for FVC were similar. Stratification of the analysis by concordance or discordance for passive tobacco smoke exposure or for frequency with which families visited one another did not systematically alter these relations. These data suggest that phenotypic similarities in pulmonary function relate directly to genetic similarities, and are consistent with a multifactorial mode of inheritance. PMID- 2923129 TI - Competing risks bias arising from an omitted risk factor. AB - The authors describe a form of selection bias that may arise when a second disease selectively removes from the population persons susceptible to the primary disease of interest. Two examples of this bias are given: 1) a lack of association between an exposure and the primary disease may appear as an inverse association, and 2) a direct association between exposure and primary disease may be greatly attenuated. These examples of bias require the presence of an unknown risk factor in addition to the exposure of interest. PMID- 2923130 TI - The case of the missing eights. An object lesson in data quality assurance. PMID- 2923131 TI - Re: "Challenges to Epidemiology in the Next Decade". PMID- 2923132 TI - Re: "Events of Reproductive Life and the Incidence of Epithelial Ovarian Cancer". PMID- 2923133 TI - Characterization of phospholipase C activity of the plasma membrane and cytosol of an osteoblast-like cell line. AB - The properties of phospholipase C (PL-C) in the plasma membranes (PM) and the cytosol of osteoblast-like osteosarcoma cells, UMR-106, were analyzed to see if separate enzymes or similar enzymes were involved in signalling, transduction, and arachidonate release. The cytosolic PL-C displayed substrate affinities in the order of phosphatidylinositol (PI) greater than phosphatidylinositol-4 phosphate (PIP) or phosphatidylinoisitol-4, 5-bisphosphate (PIP2). Hydrolysis of PI, PIP, and PIP2 by cytosolic PL-C was not affected by GTP or GTP gamma S and other nucleotides. PI hydrolysis by PM and cytosolic PL-C was undetectable in the presence of 500 microM EGTA and displayed two activity plateaus at various concentrations of Ca2+. The Km for Ca2+ in the PL-C activity of the first plateau was 0.08 microM. Significant hydrolysis of PIP2 by cytosolic PL-C was observed in the absence of Ca2+. In contrast to the enzyme(s) predominant in the cytosol, the order of substrate affinities for PM PL-C was PIP2 greater than PIP greater than PI. Only PIP2 hydrolysis by PM PL-C was stimulated by both GTP and GTP gamma S in a dose-dependent manner. PIP2 hydrolysis by PL-C of the PM was not observed in the absence of Ca2+, serving to further discriminate this enzyme activity from that of the cytosol. PIP2 hydrolysis by PL-C of the PM also was biphasic in the dependence on Ca2+. At resting cytosolic Ca2+ levels, the Vmax of the high affinity activity already had been achieved. Guanine nucleotide stimulation of PIP2 hydrolysis by PM PL-C was characterized by increased maximum activity with an unchanged Km for Ca2+ or for PIP2. The pH optimum of PIP2 hydrolysis was similar between cytosolic and PM forms of PL-C. PIP2 hydrolysis with production of IP3 (PL-C activity) in UMR-106 cells treated with [2-3H]-myoinositol was stimulated by PTH, and this stimulation was not inhibited by pertussis toxin. These data suggest that UMR-106 cells possess at least two distinct PL-C activities, one predominant in the cytosol and activated by increasing cytosolic Ca2+ with PI as the substrate. The second enzyme, a GTP-activated PIP2-specific PL-C in the plasma membranes may play an important role in hormone-induced PIP2 hydrolysis mediated through guanine nucleotide regulatory proteins and may participate in the hormonal regulation of osteoblast cytosolic Ca2+ and bone remodeling functions. PMID- 2923134 TI - Hyperuricemia, gout, and autosomal dominant polycystic kidney disease. AB - The relationship between hyperuricemia, gout, and autosomal dominant polycystic kidney disease (ADPKD) is not widely recognized. In an attempt to further clarify this relationship, the authors have studied 17 patients with ADPKD, 9 controls, 9 patients with proven gout and chronic renal failure, 11 patients with gout and normal renal function, and 11 patients with chronic renal failure. The mean serum uric acid concentration was higher in patients with ADPKD as a group than in controls (8.0 +/- 1.7 mg/dl vs. 6.4 +/- 1.6 mg/dl, p less than .02). Clinical gout was identified in 24% of patients with ADPKD; none of the patients with chronic renal failure of other etiologies had gout. Fractional excretion of uric acid and the activity of the enzyme hypoxanthine guanine phosphoribosyl transferase (HGPRT) were not different among the groups studied. From this study the authors conclude that ADPKD should be included among those diseases associated with hyperuricemia and gout. A partial deficiency in HGPRT or abnormal renal handling of uric acid do not appear to be responsible for the increased incidence of gout in patients with ADPKD. PMID- 2923135 TI - Serial bilirubin determinations as a prognostic marker in clinical infections. AB - Patients with documented serious infection and total bilirubin values of greater than 2 mg/dl were surveyed for serial changes in bilirubin and other laboratory and clinical features. Of 19 patients studied, 12 (Group A) had persisting or increasing hyperbilirubinemia, and 7 (Group B) had decline in bilirubin after infection onset. None demonstrated marked changes in other liver tests. Only one patient had infection directly involving the hepatobiliary system. There were no significant differences between the two groups with respect to underlying illnesses, active hepatobiliary diseases, pathogens, bacteremia, or administration of cholestatic drugs. All Group A patients died because of uncontrolled infections, whereas all Group B patients survived with resolution of infection (p less than .001). Ten of 15 patients with available preinfection liver tests demonstrated serial bilirubin increases without marked changes in other liver tests prior to clinical recognition of infection. These findings demonstrate that hyperbilirubinemia disproportionate to increases in other tests may manifest before recognition of infection and that persistent or progressive hyperbilirubinemia is indicative of ongoing active infection. PMID- 2923136 TI - Chronic sodium depletion increases myocardial calcium content in normotensive rats. AB - Increased myocardial contractility was found in the perfused heart isolated from sodium depleted Sprague-Dawley rats. Previously, it was reported that in vitro exposure of different cardiac preparations to low Na+ buffers was associated with both an increased contractility and an increased Ca2+ content in the cells. Therefore, this study was designed to examine increases in ventricular Ca2+ content in the hearts of chronically sodium depleted rats. Two groups of 12-week old Sprague-Dawley rats were studied. One group (n = 5) received furosemide (5 mg/kg/day IP for 4 days), a low Na+ diet and distilled drinking water for 6 weeks (low sodium plus diuretics group = LSD). The other group (n = 5) received the same low Na+ diet, but 0.5% NaCl was supplemented in drinking water (regular sodium group = RS). Body weight and blood pressure were measured weekly during the dietary period in all rats. At the end of the 6 weeks, heart weight as well as water and electrolyte contents of the heart were measured in all animals. Results showed that both body weight and heart weight were significantly lower in LSD than in RS. Moreover, ventricular Na+ content was reduced while ventricular Ca2+ content was doubled in LSD compared to RS (8.2 +/- 0.2 units vs. 9.2 +/- 0.3 units, p less than .05 and 0.45 +/- 0.13 units vs. 0.23 +/- 0.01 units, p less than .01, respectively). We conclude that in vivo sodium depletion induces an increase in ventricular calcium content; this increased myocardial calcium may be related to the increased in vitro cardiac contractility observed after chronic in vivo sodium depletion, but its distribution between intracellular and extracellular compartments needs to be determined. PMID- 2923137 TI - Financial barriers to medical care: a prospective study in a university affiliated community clinic. AB - Access to medical care in the United States is deteriorating, particularly for the poor. The authors evaluated patients who could not afford medical care recommended by physicians in a university-affiliated clinic that serves a predominantly indigent population. The authors determined the patients' demographic characteristics, their medical problems, and the types of care for which financial barriers existed. In addition, the authors compared the patients' demographic characteristics and medical illnesses with those of a control group of patients from the clinic who did not experience financial barriers to medical care. Of the 1,950 patients evaluated, 94 (4.8%) were unable to afford care recommended by their physicians. Sixty-seven percent were US citizens, 73% were unemployed, 63% had monthly family incomes of less than $500, and only 33% had health insurance. The patients had a variety of medical problems, ranging from hearing loss, for which they could not obtain hearing aids, to breast masses, for which they could not obtain mammographies or biopsies. When compared to patients who did not experience financial barriers to recommended care, the study patients tended to be poorer, more likely to be undocumented, more likely to be uninsured, and less likely to have acute, self-limited illnesses. Our findings support the argument that the nation's current piecemeal approach to providing indigent health care may lead to serious financial barriers to access in some localities. PMID- 2923138 TI - Response of pulmonary mechanics to terbutaline in patients with bronchopulmonary dysplasia. AB - Terbutaline was administered to eight ventilator-dependent infants with evolving bronchopulmonary dysplasia to determine the potential for reductions in airway resistance. The drug was administered by nebulization through the endotracheal tube. Pre-treatment and post-treatment pulmonary mechanics measurements were performed. Patients had reductions in inspiratory (-14%, p = NS), expiratory ( 47%, p less than .05) and total (-24%, p = NS) resistances. Tidal volume increased 36% (p less than .01). This study demonstrates that nebulized terbutaline can improve pulmonary mechanics in ventilator-dependent infants with evolving bronchopulmonary dysplasia. PMID- 2923139 TI - Increased hematocrit mitigates ischemic renal damage in the splenectomized dog. AB - Splenectomy (SPLX) prevents ischemic acute tubular necrosis (ATN) and peritubular capillary (PTC) congestion. This study attempts to reverse the protective effect of splenectomy in the ischemic model of ATN by increasing hematocrit before inducing ATN. Sham-SPLX, SPLX, and SPLX dogs given packed red cells to elevate hematocrit by 30% (SPLX-high hematocrit) received bilateral renal artery obstruction (RAO) for 120 minutes. Renal function was tested for 6 days post-RAO. Hematocrit in the SPLX-high hematocrit group was greater (p less than .05) than the SPLX-RAO group but did not differ from the non-SPLX group. All groups had different (p less than .05) serum creatinine levels for 48 hours post-RAO, and untreated animals differed from all the others at 144 hours. Serum creatinine was highest in untreated, lowest in SPLX-high hematocrit, and intermediate in noninfused SPLX animals. The same pattern was observed in blood urea nitrogen, creatinine clearance and renal histopathology. Fractional excretion of sodium in the SPLX groups was six times that in the intact animals (p less than .05), irrespective of hematocrit level. We conclude that increased hematocrit is protective in ischemic ATN, and does not promote PTC congestion or ATN in the SPLX animal. In addition, the protective effect of splenectomy may be mediated, in part, by mechanism(s) that alter sodium transport or osmolar excretion. PMID- 2923140 TI - Advanced upper airway obstruction caused by cervical goiter. AB - Goiters are an unusual cause of advanced upper airway obstruction. Previously described patients have been clearly symptomatic, and most have had substernal goiters. We present a patient with minimal symptoms with severe upper airway obstruction from a cervical goiter despite long-term therapy with thyroid hormone. Her spirometry exceeded criteria for urgent surgery. Patients with large goiters should have spirometry with flow-volume loop performed despite minimal or absent symptoms of respiratory distress. PMID- 2923141 TI - Severe metabolic ketoacidosis induced by starvation and exercise. PMID- 2923142 TI - Dominantly inherited childhood gigantism resembling Sotos' syndrome. AB - Excessive growth in infancy and onset of puberty at age four was observed in a boy with features resembling Sotos syndrome. Early development of secondary sexual characteristics and advanced osseous maturation were observed. The family history was significant; excessive weight gain tended to occur in female family members in association with rapid growth in infancy and childhood. A delayed insulin response to glucose was observed in both mother and sister, and diabetes developed during his mother's gestation. These observations suggest that undetermined factors associated with excessive growth may be inherited as a dominant trait with variable expression. PMID- 2923143 TI - Spontaneous arteriovenous fistula between the left common iliac artery and iliac vein. AB - A left lower quadrant bruit, reduced left dorsalis pedis pulse, and left leg edema were found in an elderly male presenting with chest pain, hypotension, heart failure, and azotemia. Measurement of cardiac output, 12.3 1/minute, systemic vascular resistance, 349 (normal, 770-1500), and arterial-mixed venous oxygen differential, 1.3 (normal, 10-20) confirmed the suspicion of AV fistula, which was shown by arteriogram to be left common iliac artery to iliac vein. Repair was accomplished without incident and the patient made an excellent recovery. This patient's AV fistula is an excellent example of a treatable cause of high output congestive heart failure. Further, his rapid recovery after fistula repair undertaken in the setting of hypotension, renal failure, and refractory heart failure emphasizes the need for aggressive surgical intervention. PMID- 2923144 TI - Physician-patient privilege: who may have access to medical records? PMID- 2923145 TI - Pathogenesis, complications and treatment of glomerulonephritis. Proceedings of the First Roma Nephrology Conference. Fiuggi, Italy, September 28-29, 1987. PMID- 2923146 TI - Renal immune deposits induced by antibodies reactive with cell-surface antigens in laboratory animals and in man. PMID- 2923147 TI - Autoimmune responses in systemic vasculitis. PMID- 2923148 TI - Ciclosporin in idiopathic nephrotic syndrome of children. PMID- 2923149 TI - The golden tapetal sheen reflex in retinal disease. AB - A mother and son with dominant cone dystrophy manifested the retinal reflexes seen in Oguchi's disease (mother) and the carrier female of X-linked retinitis pigmentosa (son). Another patient with cone dystrophy (simplex) showed localized areas of a golden reflex in each eye. A patient with juvenile macular dystrophy exhibited a diffuse golden-orange reflex throughout the posterior pole. The latter two patients did not have the Mizuo phenomenon. PMID- 2923151 TI - Reversibility of the early stages of idiopathic macular holes. AB - Three patients had a history of unilateral acute visual loss accompanied by clinical and fluorescein angiographic findings compatible with foveal sensory retinal detachment secondary to vitreofoveal traction. The reversibility of this early stage of idiopathic macular hole formation in all three eyes was associated with spontaneous release of vitreofoveal traction and with improvement in visual acuity. A localized detachment of the vitreous from the sensory retina in the macula with an associated vitreous condensation overlying the macula was evident in all three cases. PMID- 2923150 TI - Bilateral central retinal artery occlusions, disk drusen, and migraine. AB - A central retinal artery occlusion occurred in the left eye of a 25-year-old woman with migraine and bilateral intrapapillary drusen. An extensive investigation failed to establish the presence of any systemic disease or vasculopathy. Eight years later she had a central retinal artery occlusion in her right eye. Optic disk drusen and migraine may have combined to produce this patient's bilateral visual loss consequent to retinal vaso-occlusion. PMID- 2923152 TI - Diurnal variation in vision after radial keratotomy. AB - We tested eight patients who had undergone radial keratotomy with regard to refraction, keratometry, corneal thickness, and intraocular pressure one to two weeks after surgery. Patients were examined immediately after eye-lid opening at 7:30 A.M. and again at 4:00 P.M. The contralateral eye was used as a control. The treated eye was 1.48 +/- 0.24 diopters (mean +/- S.E.M.) more hyperopic at the morning examination compared to the afternoon visit, whereas the control eye had an insignificant shift (0.16 +/- 0.06 diopters). The treated eye was significantly flatter (1.37 +/- 0.19 diopters) in the morning than in the afternoon when compared to the control eyes, which were only 0.11 +/- 0.09 diopter flatter. The intraocular pressure changed insignificantly in both the treated and control eyes (-0.5 +/- 0.53 mm Hg and -0.5 +/- 0.84 mm Hg, respectively). The mean morning corneal thickness was significantly greater (5.7%) than the afternoon thickness when compared to the controls (1.7% morning increase in thickness). These data suggest that diurnal variation in corneal thickness after radial keratotomy plays a role in diurnal variation of vision in the early postoperative period. PMID- 2923153 TI - Accuracy of topographic measurements with the Optic Nerve Head Analyzer. AB - We used a plastic model of the human eye to study the accuracy with which the Optic Nerve Head Analyzer estimates the surface contour and two-dimensional size of the optic nerve head. Computer-generated contour lines were similar to the actual cross-sectional contour of plastic cups as photographed by scanning electron microscopy. The magnification error of computer-measured cup diameters was inversely related to the axial length of the model. The slope of this relationship was reduced with the use of either refraction or axial length as a correction factor for magnification error. Of the two correction factors, the former provided the closest estimation of the known diameters in the phakic model, while the latter performed better in the aphakic model. PMID- 2923154 TI - Topical carbonic anhydrase inhibitors. PMID- 2923155 TI - A technique for precise placement of laser applications in transscleral Nd:YAG cyclophotocoagulation. PMID- 2923156 TI - A 16-year follow-up in a corticosteroid-sensitive patient with glaucoma secondary to a benign adrenal adenoma. PMID- 2923157 TI - Semiconductor diode laser photocoagulation of human malignant melanoma. PMID- 2923158 TI - Malignant teratoid medulloepithelioma of the ciliary body simulating persistent hyperplastic primary vitreous. PMID- 2923159 TI - Iris pigment mosaicism in carriers of X-linked ocular albinism cum pigmento. PMID- 2923160 TI - Controlled delivery of perfluorocarbon liquids. PMID- 2923161 TI - Double upper eyelid crease with a hereditary pattern. PMID- 2923163 TI - Glass bead implantation in the scleral cavity during evisceration. PMID- 2923162 TI - Retroaponeurotic fat. PMID- 2923164 TI - Neurotrophic corneal ulcers in congenital sensory neuropathy. PMID- 2923165 TI - A benign nevus of cornea and corneoscleral limbus. PMID- 2923166 TI - Relative afferent pupillary defect induced by patching. PMID- 2923167 TI - Occlusion-induced contralateral afferent pupillary defect. PMID- 2923168 TI - Variables associated with ultraviolet transmittance measurements of intraocular lenses. PMID- 2923169 TI - Accuracy of lens power calculations with the biconvex and meniscus intraocular lenses. PMID- 2923170 TI - Wrist muscle tone and self-care skill in persons with hemiparesis. AB - The purpose of this research was to investigate the interaction between muscle tone at the wrist and self-care function in persons with hemiparesis. Dynamic and static muscle tone measurements were taken at the wrist. Self-care ability was measured with a chart review and the Klein-Bell Scale. The results of the study did not support the assumption that there is a significant relationship between muscle tone and activities of daily living for persons with hemiparesis. Perhaps other variables such as the general state of health, cognition, and perception should also be considered during the treatment of self-care. PMID- 2923171 TI - Changes in occupational role performance after a severe burn: a retrospective study. AB - Ten men with severe burn injuries were interviewed to examine their perceptions of the residual impact of severe burn on performance in self-care, home management, work, and leisure occupations within the year after rehabilitation. Three patterns of occupational role performance after a burn were identified: (a) a resumption of participation in all four occupational categories; (b) a return to independence in self-care with substantive impairment in home management, work, and/or leisure roles; and (c) substantive disruption in all occupational roles. Role loss or disruption was commonly associated with reduced endurance, intolerance for standing and walking, and impaired grip strength and upper extremity skill. Suggestions for rehabilitation programming and research are made. PMID- 2923172 TI - The scholarly productivity of occupational therapy faculty members: results of a regional study. AB - A study of the scholarly activities of 66 occupational therapy faculty members at selected academic health centers was conducted through a mailed survey. An analysis of the responses showed that (a) the respondents' primary scholarly activities were reporting research findings in refereed journal articles and presenting papers at professional meetings and (b) only a small percentage of the respondents had directed extramurally funded projects. In addition, the level of scholarly productivity of the occupational therapists was significantly lower than that of their allied health colleagues. The majority of the respondents indicated that their own academic preparation was the primary factor that encouraged their scholarly pursuits and that heavy teaching responsibility was the primary discouraging factor. The respondents indicated also that faculty scholarly activities are, and will continue to be, important considerations in academic promotion decisions. PMID- 2923174 TI - Modified Bobath sling with distal support. PMID- 2923173 TI - Pregnancy and quadriplegia: an occupational therapy home program. PMID- 2923175 TI - Making a difference: a premise of occupation and health. PMID- 2923176 TI - A single success may not predict other successes. PMID- 2923177 TI - Is relief for personnel shortages in sight? PMID- 2923178 TI - Metabolic changes of recovery. PMID- 2923179 TI - Entry level and specialized practice: a professional encounter. PMID- 2923180 TI - Biochemical evidence for programmed cell death in rabbit uterine epithelium. AB - Uterine epithelial cell proliferation, differentiation, and death are known to be regulated by estrogen and progesterone. The authors investigated a specific pattern of cell death called apoptosis, or programmed cell death, which is biochemically characterized by a specific pattern of DNA degradation. DNA isolated from endometrium of ovariectomized pseudopregnant rabbits showed a pattern of DNA cleavage at internucleosomal locations. In comparison, DNA from the endometrium of non-ovariectomized animals, as well as several other organs, did not exhibit that pattern. This biochemical evidence supports previous and present morphologic data and correlates with it. Under the experimental conditions used, only the uterine epithelial compartment of the endometrium shows apoptotic cell death, which is absent in the stromal compartment. PMID- 2923181 TI - Endothelial stimulation of intimal cell proliferation in a porcine aortic organ culture. AB - A porcine thoracic aortic organ culture system was used to study the interaction between endothelial cells (EC) and the underlying intimal smooth muscle cells (SMC). The presence of EC in organ cultures was confirmed by the ability of luminal cells to incorporate acetylated-LDL. It was found that incubation of nondenuded organ cultures in 5% fetal bovine serum for 7 days resulted in a significant increase in the mean number of intimal SMC (41.5 +/- 0.9) compared with organ cultures in which the endothelium was removed at the beginning of the experiment (denuded, 15.2 +/- 0.8). Incubation of the latter for 7 days in conditioned medium collected from nondenuded organ cultures also resulted in a significant increase in the mean number of intimal SMC (30.2 +/- 2.2). Incubation of aortic medial SMC cultures in the conditioned medium also enhanced SMC growth. Autoradiography studies at each day of the 7 days showed that intimal SMC proliferation was similar in both nondenuded and denuded organ cultures when the latter was incubated in the conditioned medium. These data suggests that in this model the secretion of a soluble mediator by dysfunctioning, injured, or proliferating endothelial cells stimulates intimal cell proliferation either directly or indirectly. PMID- 2923182 TI - Effects of formaldehyde gas on the respiratory tract of rhesus monkeys. Pathology and cell proliferation. AB - Formaldehyde is a nasal carcinogen in rats but it remains to be determined what cancer risk this chemical poses in humans. Molecular dosimetry studies of formaldehyde and cellular proliferative responses to formaldehyde-induced cytotoxicity have been studied in the rodent and are important components of the authors' ongoing research, which has now been extended to nonhuman primates, a species more analogous to humans. The present study was designed to characterize formaldehyde injury in the respiratory tract of nonhuman primates to provide a direct comparison to the toxic effects of formaldehyde in rodents. Groups of three rhesus monkeys were exposed to room air, or 6 ppm formaldehyde for 5 days per week for 1 or 6 weeks, and the respiratory tract was assessed for nature and extent of histologic responses, and changes in epithelial cell proliferation rate. Lesions were characterized by mild degeneration and early squamous metaplasia confined to specific regions of the transitional and respiratory epithelia of the nasal passages and the respiratory epithelium of the trachea and major bronchi. There was minimal progression of histologic changes between 1 and 6 weeks; however, the percent of nasal surface area affected significantly increased in the 6-week exposure group. Formaldehyde-induced lesions were associated with increases in cell proliferation rates up to 18-fold over controls, which remained significantly elevated after 6 weeks of exposure. Histologic lesions and increases in cell proliferation were most extensive in the nasal passages and were minimal in the lower airways, whereas the maxillary sinuses exhibited no evidence of a response to formaldehyde exposure. Based on the extent of lesions and cell proliferation data, it appears that the monkey is more sensitive than the rat to the acute and subacute effects of formaldehyde at 6 ppm. The absence of response in the maxillary sinuses in the monkey suggests that combining tumors of the nasal cavity and sinuses in epidemiologic studies may not be appropriate for formaldehyde cancer risk assessment. Results of this study also have provided important information for tissue sample site selection in the monkey respiratory tract for ongoing molecular dosimetry studies. PMID- 2923183 TI - M cells and granular mononuclear cells in Peyer's patch domes of mice depleted of their lymphocytes by total lymphoid irradiation. AB - The cytoarchitecture of Peyer's patches that were depleted of their lymphocytes by total lymphoid irradiation (TLI) was examined with particular attention to the effects on M cells in the follicle epithelium and on mononuclear cells in follicle domes underlying the epithelium. Five-month-old, specific pathogen-free Balb/c mice were irradiated with 200-250 rad/day, five times a week to a total dose of 3400-4250, and their Peyer's patches were either fixed for electron microscopy or frozen for immunohistochemistry 1-4 days after completion of irradiation. Control mice were examined at the same time intervals. Follicle domes of TLI mice had approximately one fourth the epithelial surface area of domes of control mice. Within the epithelium, lymphoid cells were virtually depleted after TLI, and yet the epithelium contained M cells. In control mice, most M cells were accompanied by lymphoid cells in invaginations of the apical lateral cell membrane. In TLI mice, most M cells did not have such apical-lateral invaginations and were columnar shaped. Other than lacking lymphocytes, these cells appeared to be mature M cells. Some M cells did have lymphoid cells or granular mononuclear cells below their basal membranes, adjacent to the basal lamina. Below the epithelium, the proportion of granular mononuclear cells was greatly increased following TLI. The retention of M cells and the increase in proportion of granular mononuclear cells in follicle domes are consistent with selective depletion of lymphocytes following TLI. Persistence of M cells without lymphocytic invaginations after TLI suggests that M cells can differentiate in the absence of, or at least in the presence of very few, lymphocytes, and that invagination by lymphocytes is not necessary to maintain mature M cell morphology. PMID- 2923184 TI - In vitro and in vivo growth and differentiation of clones of tracheal basal cells. AB - Studies were performed to examine the hypothesis that the basal cells in the large conducting airways function as stem cells. Basal cells were isolated from the tracheas of adult rabbits using centrifugal elutriation procedures. Such cell isolates that contained greater than 90% basal cells were plated in culture at low cell density to produce individual basal cell clones. Clones were similarly obtained from unfractionated tracheal cells (mixed tracheal cells). Basal cell and mixed cell clones were tested to compare their in vitro growth capacity and their ability to reepithelialize denuded tracheal grafts with a mucociliary epithelium. Both basal cell and mixed cell clones underwent 15 to 20 population doublings in culture. The sizes of their clonogenic cell compartments were roughly similar. When inoculated into denuded tracheal grafts, both types of clones were equally efficient in establishing a mucociliary epithelium. The major secretory cell types observed in tracheas repopulated with the two types of cell clones were cells containing small secretory granules and either rough or smooth endoplasmic reticulum. Goblet cells were seen in approximately 40% of tracheas repopulated with either of the two types of cell clones. It is concluded that in rabbits tracheal basal cells can generate secretory cells with varying morphologic characteristics as well as ciliated cells and may be regarded as epithelial stem cells. PMID- 2923185 TI - Sequential ultrastructural changes of the pancreas in zinc toxicosis in ducklings. AB - The sequential ultrastructural alterations of the pancreas in zinc toxicosis were examined in ducklings fed 2500 ppm Zn (as ZnSO4) for 56 days. From days 3 to 17, acinar cells had cytoplasmic vacuoles that contained electron-dense, zymogen-like material and increased autophagocytosis. Other changes were swollen mitochondria and dilatation, vesiculation, degranulation and intracisternal sequestration of rough endoplasmic reticulum. Apoptosis was the predominant form of cell deletion. By day 10, acinar cellular atrophy and interstitial fibrosis were noted. Islets appeared normal. After day 19, the pancreas consisted of ductlike structures embedded in fibrous connective tissue with a minimal inflammatory cell response. These ductlike structures were lined by attenuated to cuboidal, atrophic acinar cells. Many cells contained granular, electron-dense cytoplasmic debris that served as a marker of previous cell damage. This ultrastructural study provides support for a previously proposed theory that ductlike structures (tubular complexes) arise by atrophy and dedifferentiation of acinar cells. PMID- 2923187 TI - Demonstration of early ischemic injury in porcine right ventricular myocardium. AB - Past studies of acute canine right ventricular (RV) ischemia have failed to demonstrate early irreversible injury or decreased function; however, the dog has extensive collateral circulation that may attenuate RV myocardial injury. The aim of this study was to measure RV function using contrast ventriculography and assess myocardial injury by immunohistochemical evaluation of creatine kinase (CK), lactate dehydrogenase (LDH), and tropomyosin (TROP) as well as by electron microscopy after right coronary occlusion in 14 closed-chest pigs. Significant depression in RV ejection fraction and stroke volume index after 10 minutes and was observed (P less than 0.05). CK, LDH, and TROP were positive in control tissue with a diminution of CK and LDH staining along the subendocardium after 15 minutes of ischemia. Irreversible ultrastructural injury in conjunction with large losses of CK and LDH became evident after 30 minutes. Thus, in the pig, which has a coronary anatomy similar to humans, significant RV dysfunction and irreversible myocardial injury can be demonstrated after 15 to 30 minutes of ischemia. PMID- 2923186 TI - Directed exocytosis of secretory granules containing apolipoprotein E to the adherent surface and basal vacuoles of macrophages spreading on immobile immune complexes. AB - As macrophages spread on an immune complex-coated surface, large, clear basal vacuoles and numerous coated vesicles and tubules form rapidly and are occasionally contiguous with the adherent surface, creating a microcompartment between the immune complex-coated surface and the cell membrane. The present study explored the nature of this basal compartment by examining the distribution of a major secretory product of macrophages, apolipoprotein E (ApoE), and of a lysosomal enzyme, acid phosphatase, by enzyme and immunocytochemistry. Upon contact of the macrophages with the immune complexes, intracellular stores of ApoE were secreted rapidly in the first 10 to 20 minutes to the area of ligand receptor interaction. ApoE filled the large basal vacuoles and was also found in invaginations on the adherent surface that were sealed to the influx of proteins and peptides from the bulk medium. In contrast, the contents of lysosomes were not redistributed to the basal compartment. By 2 hours most of the ApoE had appeared in the bulk medium, suggesting that the protein could move out of the basal compartment. These data suggest that specific ligand-Fc receptor interactions serve to target secretion by macrophages to selective focal areas of contact, and that there are also mechanisms for retrieval of material from these sites. PMID- 2923188 TI - Time-related changes in microsphere entrapment in canine jejunum. AB - To assess the validity of repeated blood flow measurements using the microsphere technique, the apparent blood flows in the anatomic layers of the jejunum were determined from the entrapment of 9-, 11.5-, and 17-micron microspheres at 1.5, 15, 30, and 60 min after their injection. The entrapment of 17-micron spheres in the mucosa plus submucosa and in the muscularis propria remained similar at all times, but these spheres migrated (P less than 0.01) from the submucosa to the mucosa. By 1.5 min, 5 +/- 2% of 11.5-micron spheres had shunted, but no subsequent shunting was observed. No migration of 11.5-micron spheres from the mucosa, submucosa or the muscularis was observed. The shunting of 9-micron spheres from the whole wall increased from 19 +/- 4% at 1.5 min to 40 +/- 4% at 60 min (P less than 0.001). These data suggest that 17-micron spheres can only fractionate the blood flow of the whole wall into that of the mucosa plus submucosa and that of the muscularis propria, while 11.5-micron spheres may measure fractional flow to the submucosa separately. The continued washout of 9 micron microspheres precludes their use for repeated blood flow measurements. PMID- 2923189 TI - Sulfate transport in human lung fibroblasts (IMR-90): effect of pH and anions. AB - We previously reported the presence of a carrier-mediated sulfate transport system in human lung fibroblasts (IMR-90) (A. Elgavish, J. B. Smith, D. J. Pillion, and E. Meezan. J. Cell. Physiol. 125: 243-250, 1985). Kinetic studies carried out in the lung fibroblasts show that Cl- inhibits SO4(2-) uptake in a competitive manner. Taken together with the fact that high extracellular Cl- stimulates SO4(2-) efflux, these results suggest that SO4(2-) uptake into lung fibroblasts occurs via a SO4(2-)-Cl- exchange mechanism. Extracellular HCO3- inhibits sulfate influx in a competitive manner (pH 7.5) but has no marked effect on sulfate efflux. SO4(2-) and HCO3- may therefore have the ability to bind to a common extracellular anion binding site, but they do not appear to exchange for one another. Lowering extracellular pH has a stimulatory effect on the initial rate of sulfate uptake. The pK of the extracellular pH effect is around pH 7.0, indicating that small changes in the extracellular pH around the ambient levels encountered under physiological conditions will markedly affect sulfate influx into the cell. Kinetic studies suggest that lowering extracellular pH increases the initial rate of sulfate influx by increasing the affinity of the carrier for sulfate twofold. Lowering intracellular pH inhibits the initial rate of sulfate influx into the cell. The pK of this intracellular pH effect is also around pH 7.0, indicating that physiological levels of intracellular protons are necessary for the normal activity of the anion exchanger.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2923190 TI - Rat lung lectin gene expression is regulated developmentally and by dexamethasone. AB - The cell-agglutinating activity of soluble beta-galactoside-binding proteins (lectins) is developmentally regulated in several mammalian organs. Little is known of the alterations in gene expression that underlie this developmental regulation. Rat lung contains a dimeric beta-galactoside-binding protein that exhibits a postnatal peak of hemagglutination activity caused in part by an increased rate of lectin synthesis. We now report rat lung lectin mRNA concentration increased to a peak at age 6 days; dexamethasone treatment aborted this increase. Southern blot analysis is compatible with the presence of more than one lectin gene. However, two lines of evidence indicate that we measured a single gene product: 1) only one lectin of subunit Mr 14,000 is present in rat lung (Biochemistry 27: 692-699, 1988), and 2) in Northern blot analysis of RNA, the lectin cDNA hybridized with only one mRNA species. Our present findings, taken with prior studies of lectin synthesis, indicate that the postnatal increase in lectin synthesis is mediated pretranslationally and by an increased efficiency of translation. Dexamethasone treatment impairs the increase of lectin mRNA concentration but increases translational efficiency. PMID- 2923191 TI - Density-independent isolation of type II pneumocytes after partial pneumonectomy. AB - Type II pneumocytes were isolated by immunoglobin G (IgG) panning from the lungs of normal rats and the right lung of rats (180-200 g) subjected to left pneumonectomy. Cells were studied at 7 (pnx-7) and 15 (pnx-15) days postoperative, times during and after, respectively, rapid compensatory growth of the right lung. After 24 h of primary culture, pnx-7 cells contained 32% more protein per DNA, and incorporated thymidine at a rate 224% greater than cells isolated from control rats. Both the protein-to-DNA ratio and thymidine incorporation returned to control values in pnx-15 cells. Uptake of exogenous spermidine also was increased by 50% in pnx-7 cells at 24 h of primary culture and returned to control values in pnx-15 cells. Increased spermidine uptake was due to an increase in the maximal velocity (Vmax) of transport from 30.3 (control) to 45.5 pmol.micrograms DNA-1.h-1 (pnx-7), with no change in the apparent Km of 1.32 microM. No change was observed in the relative rates of phospholipid or neutral lipid biosynthesis. The increases in thymidine incorporation and spermidine uptake were significantly greater than those previously observed [Am. J. Physiol. 254 (Cell Physiol. 23): C684-C690, 1988] in pnx-7 cells isolated by Percoll gradient sedimentation. These results suggest that pnx-7 lungs contain distinct subpopulations of type II pneumocytes, the recovery of which is dependent on the cell isolation protocol employed. PMID- 2923192 TI - A fluorescent indicator for measuring cytosolic free magnesium. AB - The previously developed chelator O-aminophenol-N,N,O-triacetic acid (APTRA) (L. A. Levy, E. Murphy, B. Raju, and R. E. London. Biochemistry 27: 4041-4048, 1988) has been modified to yield a fluorescent analogue which can be utilized as an intracellular probe for ionized Mg2+. The fluorescent analogue, FURAPTRA, with a magnesium dissociation constant of 1.5 mM, is structurally analogous to the calcium chelator fura-2 and exhibits a similar excitation shift on magnesium complexation. Hence, data on the intracellular Mg2+ concentration can be obtained using an analogous ratio method. The acetoxymethyl form of the chelator is readily loaded into cells and has been used to determine a cytosolic free Mg2+ concentration of 0.59 mM for isolated rat hepatocytes. As a consequence of the relatively high levels of cytosolic Mg2+, the problem of ion buffering is much less severe than for the analogous calcium indicators. PMID- 2923193 TI - Autoxidation, dehydration, and adhesivity may be related abnormalities of sickle erythrocytes. AB - The sickle gene has remarkably pleiotropic effects. In an attempt to understand the complex pathobiology of sickle disease, we have searched for potential relationships between various cellular abnormalities. In the present studies, we treated normal erythrocytes (RBCs) with phenazine methosulfate to stimulate intracellular generation of superoxide and thereby stimulate the excessive autoxidation characteristic of sickle RBCs. In response, RBCs show a dose dependent increase in adherence to endothelium, easily achieving the degree of abnormal adherence typical of unmanipulated sickle RBCs. This is mediated by adverse effects of oxidant on cellular hydration, as evidenced by amelioration of abnormal adhesivity if the drug's dehydrating effect is inhibited. Consistent with potential relevance of this to sickle pathobiology, the abnormal endothelial adherence of sickle RBCs can be worsened or improved by dehydrating or hydrating these cells, respectively. These data suggest an intimate relationship between three abnormalities of sickle RBCs previously thought to be unrelated (autoxidation, dehydration, and adhesivity). Although multiple mechanisms may contribute to abnormal cell-cell interactions in sickle disease, the potentiation of sickle RBC adhesivity by cellular dehydration may help explain why clinical dehydration has been identified as a precipitant of vasocclusive crisis. Insofar as abnormal adhesivity participates in the sickle vasocclusive process, these data provide further rationale for attempting to manipulate RBC hydration as a therapeutic maneuver in this disease. PMID- 2923194 TI - Lack of endothelium-dependent relaxation in coronary resistance arteries of cholesterol-fed rabbits. AB - The endothelium-dependent contractile responses of subepicardial coronary resistance arteries (286 +/- 18 microns ID, n = 22) from rabbits fed either a 0.5 or 2.0% cholesterol-enriched diet or a control diet for 10-12 wk were determined under isometric conditions at the optimum length for active force production (Lo). After the development of tone with 29 mM K+-Krebs, arteries from control rabbits treated with acetylcholine (0.1-10 microM) showed a concentration dependent relaxation, with a maximum decrease in tone of 63%. In contrast, coronary arteries from animals fed 0.5 and 2.0% cholesterol contracted to acetylcholine (approximately 210% increase in tone). A similar phenomenon was seen with arteries precontracted with 10 nM 9,11-methanoepoxy-prostaglandin H2 (U 46,619), a thromboxane A2 mimetic. The contractile responses to acetylcholine occurred in arteries in which the endothelium was structurally intact and which were devoid of plaque. Arteries from cholesterol-fed animals were poorly responsive to ADP (0.01-10.0 microM), whereas arteries from normal animals relaxed. All arteries relaxed to an equal degree when exposed to acidified nitrite, which produces nitric oxide (NO). The data suggest that as a result of hypercholesterolemia, there may be a dysfunction in the synthesis or release of endothelium-derived relaxing factor (EDRF) by the endothelial cells of coronary resistance arteries, rather than an abnormality of the smooth muscle cells per se. PMID- 2923195 TI - Matrix-derived soluble components influence type II pneumocytes in primary culture. AB - Type II pulmonary epithelial cells cultured on a plastic surface fail to retain differentiated form and function. During the first 3 days in primary culture, the cells flatten and lose characteristic lamellar inclusions; they increase in size and exhibit accelerated rates of protein synthesis and thymidine incorporation. These transitions are inhibited markedly if the cells are plated on matrigel (MG), a laminin-rich surface derived from the Englebreth-Holm-Swarm (EHS) sarcoma. Soluble components released from matrigel (MGS) mimic some of the effects of the solid gel. As on a plastic surface, the cells flatten when exposed to MGS during culture. In contrast, MGS inhibits thymidine incorporation and protein synthesis; it is most effective when added early in the culture interval. Direct contact of the cells with the matrigel surface itself is always more effective than maximal MGS activity. The effects of MGS are not reproduced by purified laminin or by transforming growth factor-beta, both of which are present in matrigel. These results indicate that the effects of the solid matrigel surface on cell morphology are caused in part by direct cell-matrix contact but that additional effects, such as decreased DNA synthesis, can be mediated by activity of solubilized gel components. They further provide a model wherein changes in type II cell morphology and function, which typically occur in parallel during primary culture, can be separated experimentally. PMID- 2923196 TI - Alanine transport systems in isolated basal plasma membrane of human placenta. AB - Concentrative transfer of amino acids from mother to fetus is affected by transport across both microvillous (maternal-facing) and basal (fetal-facing) plasma membranes of the human placental syncytiotrophoblast. Isolated basal plasma membrane vesicles were used to elucidate transport systems for neutral amino acids across this membrane. The concentration dependence and inhibition of zero-trans-alanine uptake were studied and four pathways for alanine uptake were defined as follows: 1) a sodium-dependent system shared by methylaminoisobutyric acid, which has the characteristics of an A system; 2) a sodium-dependent system resistant to inhibition by methylaminoisobutyric acid, which has the characteristics of an ASC system; 3) a sodium-independent system which may resemble an L system; 4) nonsaturable uptake. The microvillous membrane of the syncytiotrophoblast possesses systems similar to 1 and 3, but system 2 is unique to the basal plasma membrane. Active and passive transport of amino acids across both microvillous and basal plasma membranes may contribute to trophoblast amino acid uptake and nutrition and to the transfer of amino acids to the fetus. PMID- 2923197 TI - Na+-Ca2+ exchange in cardiac sarcolemma: modulation of Ca2+ affinity by exercise. AB - The high activity of the cardiac Na+-Ca2+ exchanger has led to the suggestion that it plays an important role in the regulation of myocardial contractility. We have proposed that exercise training increases stroke volume as a consequence of an enhanced contractility caused by an adaptation in Ca2+ transport across the cardiac plasma membrane (sarcolemma). The present study examined the possibility that the Na+-Ca2+ exchanger in heart muscle is modified in response to training. Sprague-Dawley rats (female, n = 72) were randomly divided into exercise-trained (T) and sedentary control (C) groups. As a result of the 11-wk treadmill-training paradigm, group T had a 7.6% higher (P less than 0.005) heart-to-body weight ratio and a 36% increase (P less than 0.01) in gastrocnemius mitochondrial enzyme activity. Na+-Ca2+ exchange was studied in highly purified sarcolemmal vesicles using rapid-quenching techniques. The absolute initial rate of uptake was significantly higher in T vs. C at calcium concentrations [( Ca2+]) ranging from 10 to 80 microM. This increased uptake appears to be due solely to the fact that the apparent Km of the myocardial Na+-Ca2+ exchanger for Ca2+ was significantly lower in T vs. C (15.7 +/- 1.1 vs. 36.1 +/- 2.6 microM), since the maximum velocity was unchanged. The observed increase in the affinity of the exchanger for Ca2+ is not attributable to group differences in vesicular purity, cross contamination, or passive Ca2+ efflux. This observation is consistent with observed alterations in sarcolemmal composition in response to exercise training. We propose that the modification of the Na+-Ca2+ exchanger may play an important role in the adaptation of the heart to exercise. PMID- 2923198 TI - Density-dependent hyperpolarization in cultured aortic smooth muscle cells. AB - The membrane potential (Em) of cultured aortic smooth muscle cells from Sprague Dawley (SD), Wistar-Kyoto (WKY), and spontaneously hypertensive (SHR) rats was measured in proliferating primary cultures. Em of SD cells in high-density cultures was -51 to -58 mV, whereas that of low-density cultures (1-2 days) was 30 mV. This difference was due to a continuous process of hyperpolarization during proliferation in culture. Em of WKY and SHR hyperpolarized similarly, from -12 to -42 and -38 mV, respectively. Hyperpolarization of Em of SD, WKY, and SHR cells was related to cell density rather than time in culture. Em may be a sensitive and significant indicator of the changes in the differentiated state expressed by proliferating smooth muscle in vitro. PMID- 2923199 TI - Skeletal muscle growth is stimulated by intermittent stretch-relaxation in tissue culture. AB - Avian pectoralis muscle cells differentiated in vitro are mechanically stimulated by repetitive stretch-relaxation of the cell's substratum using a computerized mechanical cell stimulator device. Initiation of mechanical stimulation increases the efflux of creatine kinase from the cells during the first 8-10 h of activity, but the efflux rate returns to control levels after this time period. Decreased total cell protein content accompanies the temporary elevation of creatine kinase efflux. With continued mechanical stimulation for 48-72 h, total cell protein loss recovers and significantly increases in medium supplemented with serum and embryo extract. Myotube diameters increase and cell hyperplasia occurs in the stimulated cultures. In basal medium without supplements, mechanical activity prevents myotube atrophy but does not lead to cell growth. Mechanically induced growth is accompanied by significant increases in protein synthesis rates. The increases in protein synthesis and accumulation induced by mechanical stimulation are not inhibited by tetrodotoxin but are significantly reduced in basal medium without supplements. Mechanically stimulated cell growth is thus dependent on medium growth factors but independent of electrical activity. PMID- 2923200 TI - Two distinct mechanisms are responsible for single K channel block by internal tetraethylammonium ions. AB - Tetraethylammonium (TEA) ions blocked the unitary currents through the delayed rectifier potassium channels of Drosophila neurons from the cytoplasmic side of inside-out membrane patches by two distinct mechanisms. First, TEA attenuated the single-channel conductance, probably by producing very rapid block-unblock reactions at the inner mouth of the potassium pore. Second, TEA markedly enhanced the slow inactivation, making the incidence of channel openings highly nonrandom; blank traces with no channel openings during repetitive depolarizations showed a significant tendency to be clustered in the presence of TEA. This second action accounts for almost half of the reduction of average current produced by 10 mM internal TEA. PMID- 2923201 TI - Tight monolayers of rat alveolar epithelial cells: bioelectric properties and active sodium transport. AB - Because the pulmonary alveolar epithelium separates air spaces from a fluid filled compartment, it is expected that this barrier would be highly resistant to the flow of solutes and water. Investigation of alveolar epithelial resistance has been limited due to the complex anatomy of adult mammalian lung. Previous efforts to study isolated alveolar epithelium cultured on porous substrata yielded leaky monolayers. In this study, alveolar epithelial cells isolated from rat lungs and grown on tissue culture-treated Nucleopore filters resulted in tight monolayers with transepithelial resistance greater than 2,000 omega.cm2. Changes in bioelectric properties of these alveolar epithelial monolayers in response to ouabain, amiloride, and terbutaline are consistent with active sodium transport across a polarized barrier. 22Na flux measurements under short-circuit conditions directly confirm net transepithelial absorption of sodium by alveolar epithelial cells in the apical to basolateral direction, comparable to the observed short-circuit current (4.37 microA/cm2). The transport properties of these tight monolayers may be representative of the characteristics of the mammalian alveolar epithelial barrier in vivo. PMID- 2923202 TI - Water movement: does thermodynamic interpretation distort reality? AB - In a recent theoretical analysis of water flow, Finkelstein (Water Movement Through Lipid Bilayers, Pores, and Plasma Membranes: Theory and Reality, 1987) has attacked the contributions of irreversible thermodynamics, stating that "the thermodynamic treatment of uphill water flow completely distorts reality." Instead he presents a mechanistic formulation. For a porous membrane, water flow is attributed to convection generated by a favorable hydrostatic pressure gradient within pores, even when in the presence of permeant solutes water moves against its chemical potential gradient; water flow may "drag", solute, to an extent determined by the solute partition coefficient, but the possibility that solute flow may drag water is excluded. We argue that this formulation violates the second law of thermodynamics. Water cannot move against its chemical potential gradient because of the influence of only part of the chemical potential gradient. Furthermore, the proposed mechanism requires that at one of the membrane-solution interfaces water must move against both its concentration gradient and the hydrostatic pressure gradient. Also considered by Finkelstein is the nature of the reflection coefficient sigma, a kinetic variable, which he concludes can be evaluated (in a porous membrane) by measurement of the (equilibrium) solute partition coefficient. We claim that in general it is not possible to evaluate a kinetic variable from measurements of equilibrium parameters alone. A valid kinetic analysis must incorporate the contribution of all coupled flows. PMID- 2923203 TI - Water movement: does thermodynamic interpretation distort reality? PMID- 2923204 TI - Oxygen consumption after massive sympathetic nervous system discharge. AB - We evaluated the possibility that massive, sympathetic nervous system (SNS) activation [as may precede the development of neurogenic pulmonary edema (NPE)] increases O2 demand. O2 consumption (VO2) and plasma concentrations of the calorigenic agents, epinephrine (EPI) and norepinephrine (NE) were measured in alpha-chloralose-anesthetized dogs under control conditions and for 3 h after the administration of either 1) intracisternal (ic) veratrine to activate the SNS, 2) intravenous (iv) veratrine, 3) ic saline, or 4) ic veratrine, after clamping the adrenal blood vessels. VO2 increased 31.7 +/- 3.6% (SE), and EPI and NE increased to, respectively, 30,853 +/- 8,347 and 8,176 +/- 2,104 pg/ml in the ic veratrine group. No increases in VO2 and EPI and attenuated increases in NE were observed in the ic veratrine animals with clamped adrenals. No significant increases in VO2 or catecholamine concentrations were observed after ic saline or iv veratrine administration. These data suggest that the elevated VO2 may have been mediated by adrenal catecholamines and that an increased metabolic rate may complicate the ability of patients with severe NPE to balance O2 supply with demand. PMID- 2923205 TI - Alterations of fasting glucose and fat metabolism in intrauterine growth-retarded newborn dogs. AB - Maternal nutritional deprivation resulted in reduced fetal weight at term gestation (251 +/- 7 vs. 277 +/- 7 g, P less than 0.01) in newborn dogs. Growth retarded pups developed lower blood glucose levels after 3, 6, and 9 h of neonatal fasting, reduced plasma levels of free fatty acids (FFA) at 9 and 24 h, and lower ketone bodies at 24 h compared with age-matched newborn control pups. Systemic rates of palmitate and alanine turnover were not affected, but systemic glucose turnover was reduced for 3-9 h after birth. The rate of alanine incorporation into glucose from 3 to 9 h was also reduced in growth-retarded pups compared with timed controls. Paradoxically, the rate of incorporation of palmitate into triglycerides was augmented in the smaller growth-retarded pups. Hepatic glycogen content was reduced at every time in the study among growth retarded pups, whereas the rates of glycogenolysis between birth and 24 h were equivalent in the two pup groups. In contrast, hepatic triglyceride levels were augmented throughout the study in pups with growth retardation. Maternal starvation and lower glucose levels resulted in a lower hepatic energy charge, and augmented cytoplasmic and mitochondrial NAD-to-NADH ratios in intrauterine growth-retarded pups. These data suggest that intrauterine growth retardation in dogs results in fasting neonatal hypoglycemia that is due in part to reduced systemic glucose production. We speculate that reduced rates of gluconeogenesis from alanine and reduced oxidation of alternate fuels such as FFA contribute to hypoglycemia. FFA recycling to triglyceride synthesis rather than oxidative pathways may contribute to the observed reduction of circulating glucose levels. PMID- 2923206 TI - Reciprocal changes of muscle oxidases and liver enzymes with recovery from iron deficiency. AB - We determined the recovery time courses of muscle oxidases and liver enzymes after iron administration to iron-deficient rats. Female 21-day-old Sprague Dawley rats were fed an iron-deficient (3 mg Fe/kg) or a control (50 mg Fe/kg) diet for 3 wk. The deficient rats were then injected with 50 mg Fe as iron dextran/kg body wt (Fe-T) or saline (Fe-) intraperitoneally. At 16, 40, 64, 112, and 180 h after injection, blood and tissue samples were taken to determine hemoglobin concentration (Hb), gastrocnemius glycolytic enzyme and oxidase activities, and liver amino acid catabolic enzyme activities. No changes were observed in any parameter across time in either the Fe- or control (Fe+) rats. In the Fe- rats, Hb, pyruvate + malate (P + M), 2-oxoglutarate (2-OG), and succinate oxidases (SO) were depressed to 33, 36, 44, and 7% of Fe+, respectively (P less than 0.05). At 16 h, Fe-T values were significantly elevated compared with Fe- rats but still only 40, 48, 55 and 10% of controls, respectively. Glutamate dehydrogenase (GDH) and alanine aminotransferase (AAT) of Fe- rats were 174 and 134% of control values (P less than 0.05). By the 180-h time point, Hb, P + M, 2 OG, and SO of Fe-T rats increased to 99, 84, 89, and 43% of Fe+ values, whereas GDH and AAT activities declined to 111 and 106% of controls. Glycolytic enzymes showed no systematic changes with iron deficiency or after iron administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2923208 TI - Effect of sepsis on activity of pyruvate dehydrogenase complex in skeletal muscle and liver. PMID- 2923207 TI - Developmental changes in adrenergic regulation of fetal arginine vasopressin secretion. AB - Fetal adaptation to the extrauterine environment is associated with profound alterations in pulmonary, renal, and cardiovascular functions. Coincident with these changes are a variety of endocrine responses including concomitant increases in plasma catecholamine and arginine vasopressin (AVP) levels. In view of the demonstrated interaction between the sympathoadrenal system and the neurohypophysis in adult mammals, we questioned whether increases in plasma catecholamine levels in the fetus affect fetal plasma AVP levels and whether catecholamine-AVP interactions change developmentally. Chronically catheterized fetal lambs at either 131 +/- 1 (preterm) or 142 +/- 1 days (term) received graded infusions of either epinephrine (E) or norepinephrine (NE) at rates of 0.04, 0.2, 0.75, 1.5, and 3.0 micrograms.min-1.kg-1 during successive 40-min infusion periods. Plasma AVP concentrations in term animals significantly increased (1.4 +/- 0.1 to 5.1 +/- 1.6 pg AVP/ml) in response to E infusion of 0.75 microgram.min-1.kg-1 or greater. The log-linear dose response curves for each animal were used to determine the minimum plasma E concentration required to stimulate AVP secretion or "threshold." The mean plasma E threshold for AVP secretion was significantly lower in term animals (1.4 +/- 0.4 ng/ml) than in preterm animals (6.6 +/- 0.9 ng/ml). Plasma E levels were positively correlated with plasma AVP levels (r = 0.90) above the threshold value in both groups. Changes in plasma AVP levels were observed in preterm or term animals in response to NE only at the highest infusion rate studied.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2923209 TI - Effects of ethanol on amino acid transport in basolateral liver plasma membrane vesicles. AB - Ethanol has been reported to inhibit hepatocellular processes such as gluconeogenesis and protein synthesis that depend, in part, on amino acid uptake. Since previous studies in cultured hepatocytes indicate that ethanol may have a direct and selective inhibitory effect on amino acid transport, the effects of ethanol on amino acid uptake into basolateral (sinusoidal) rat liver plasma membrane (blLPM) vesicles were examined. Uptake of [3H]alanine, [3H]leucine, and [35S]cysteine was measured by a rapid Millipore filtration technique in the presence of inwardly directed Na+ and K+ gradients and under tetramethylammonium (TMA+)- and Na+-equilibrated conditions. Ethanol preincubation produced a concentration-dependent inhibition of Na+-dependent alanine and cysteine uptake; no effect was observed on either Na+-independent alanine and cysteine uptake or Na+-independent leucine transport. Ethanol had no effect on L-alanine transport under Na+-equilibrated conditions; however, initial rates of 22Na flux were enhanced in the presence of ethanol. On the basis of differences in 2 (methylamino)isobutyrate and L-cysteine sensitivity, ethanol inhibition of Na+ dependent alanine transport in blLPM vesicles largely but not exclusively corresponded to the hormone-responsive system A for amino acid transport described in isolated hepatocytes. Kinetic analysis showed that ethanol treatment resulted in an alteration in the apparent maximum velocity of reaction (Vmax) of Na+-dependent alanine transport without affecting the apparent Km for alanine. The inhibitory effects of ethanol on the time course of Na+-dependent alanine uptake were reversible.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2923210 TI - Electrophysiological evidence for Na+-coupled bicarbonate transport in cultured rat hepatocytes. AB - Recent observations suggest that hepatocytes exhibit basolateral electrogenic Na+ coupled HCO3- transport. In these studies, we have further investigated this transport mechanism in primary culture of rat hepatocytes using intracellular microelectrodes to measure membrane potential difference (PD) and the pH sensitive fluorochrome 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein to measure intracellular pH (pHi). In balanced media containing 25 mM HCO3-, PD averaged 32.1 +/- 0.6 (SE) mV and pHi averaged 7.22 +/- 0.03. PD became more negative (hyperpolarized) when extracellular [HCO3-] was increased and less negative (depolarized) when extracellular HCO3- was decreased. Acute replacement of extracellular Na+ by choline also resulted in membrane depolarization of 18.0 +/- 1.6 mV, suggesting net transfer of negative charge. This decrease in PD upon Na+ removal was HCO3- -dependent, amiloride insensitive, and inhibited by the disulfonic stilbene 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS). PD also decreased upon acute exposure to SITS. The degree of depolarization seen with removal of Na+ or HCO3- correlated directly with resting PD (r = 0.81 and 0.95, respectively), suggesting a voltage-dependent mechanism. Removal of extracellular Na+ also decreased pHi to 7.06 +/- 0.02, and this acidification was decreased in the absence of HCO3- or in the presence of SITS or amiloride. These studies provide direct evidence for electrogenic Na+-coupled HCO3- transport in rat hepatocytes. Further, they suggest that it represents a major pathway for conductive movement of Na+ across the membrane and that it contributes, along with Na+-H+ exchange, to the intracellular acidification observed upon removal of extracellular Na+.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2923211 TI - Brush-border inositol transport by intestines of carnivorous and herbivorous teleosts. AB - Transport characteristics of myoinositol by isolated brush-border membrane vesicles of two fish, the herbivorous tilapia (Oreochromis mossambicus) and the carnivorous eel (Anguilla anguilla), were measured. [3H]myoinositol uptake by vesicles of both fish was stimulated by a transmembrane Na gradient, was electrogenic, and was inhibited by phloridzin. Kinetic analysis of myoinositol influx disclosed species differences (tilapia, K = 0.15 mM, Jmax = 0.2 nmol.mg protein-1.min-1; eel, K = 2.6 mM, Jmax = 0.8 nmol.mg protein-1.min-1). D-glucose inhibition of myoinositol influx was shown to be noncompetitive. Additional inhibition studies with a range of sugars demonstrated that aldohexoses in the C 1 chair conformation were preferred substrates. Myoinositol had no effect on D glucose transport. Preloading vesicles with myoinositol transstimulated [3H]myoinositol uptake, while the use of internal D-glucose was without effect. These results suggest that the intestinal brush border may have a pathway for myoinositol transport entirely separate from that for D-glucose but inhibited by D-glucose via binding to a regulator site on the myoinositol transporter. Markedly dissimilar influx kinetic constants suggest possible differences in myoinositol needs by carnivorous and herbivorous fish. PMID- 2923212 TI - Basolateral inositol transport by intestines of carnivorous and herbivorous teleosts. AB - Myoinositol transport by isolated basolateral membrane vesicles was characterized from intestines of the herbivorous tilapia (Oreochromis mossambicus) and the carnivorous eel (Anguilla anguilla). [3H]myoinositol transport occurred by nonelectrogenic, facilitated diffusion independent of cation gradients and was inhibited by phloretin (Ki = 0.6 and 0.9 mM for tilapia and eel, respectively) but not by phloridzin. Kinetic analysis of myoinositol influx disclosed no differences in concentration yielding half-maximal influx or maximum influx between these species. D-Glucose inhibition of myoinositol influx was shown to be noncompetitive. Additional inhibition studies with a range of sugars demonstrated that aldohexoses in the C-1 chair conformation were preferred substrates. Myoinositol had no inhibitory effect on D-glucose transport. Preloading vesicles with myoinositol transstimulated [3H]myoinositol uptake, while the use of internal D-glucose was without effect. These basolateral data support the contention that epithelial myoinositol carriers are separate from D-hexose transport systems present on the same membrane but are modulated by hexose binding to a regulator site on the myoinositol transporter. Furthermore, the comparison of two fish species suggests that genetic dietary transport adaptation occurs on the brush-border membrane, while no such adaptation is present at the epithelial basolateral pole. PMID- 2923214 TI - Changes in hepatic blood volume on galactose and indocyanine green uptake by cat liver. AB - The liver has important functions as a blood volume reserve and in uptake and metabolism of many substrates. This study examines whether changes in hepatic blood volume modify the uptakes of model substrates galactose and indocyanine green (ICG) in cats anesthetized with pentobarbital sodium. A hepatic venous long circuit technique with an extracorporeal reservoir was used to control hepatic flow and venous pressure and to allow repeated sampling of arterial, portal, and hepatic venous blood without depletion of the cat's blood volume. Hepatic blood volume was measured by plethysmography. Galactose and ICG were infused intravenously at constant rates for 200 min in each of three series of experiments. The first series were time controls. In the second series, hepatic blood volume was increased by raising hepatic venous pressure. In the third series hepatic blood volume was decreased by hepatic nerve stimulation and infusions of norepinephrine and angiotensin. Hepatic congestion resulted in small increases in blood galactose levels, suggesting mild impairment of hepatic galactose metabolism. Decreases in liver blood volume did not modify hepatic galactose metabolism. Increases in hepatic blood volume facilitated while decreases inhibited ICG uptake, but the effects were small. Sinusoidal velocity and transit time have minor effects on uptake even for protein-bound substrates. In summary, large changes in hepatic blood volume had minor effects on galactose and ICG blood concentrations, suggesting that the metabolic functions of the liver are essentially independent of the blood reservoir function. PMID- 2923213 TI - Identification and characterization of a pancreatic intrinsic factor in the dog. AB - An intrinsic factor has been identified in the canine pancreas, and output and properties of this protein have been compared with those of gastric intrinsic factor in the dog. Mean concentrations of intrinsic factor and peak outputs per minute were approximately 5- to 10-fold higher in pure pancreatic juice after stimulation with secretin and cholecystokinin, respectively, than in pentagastrin stimulated gastric juice. Purified gastric and pancreatic intrinsic factors had an identical molecular mass of 65 kDa, estimated by gel filtration on Sephacryl S 200, while sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated single bands corresponding to 53 kDa. Immunoblots showed that rabbit polyclonal antiserum to canine gastric intrinsic factor cross-reacted with canine pancreatic intrinsic factor. Gastric and pancreatic intrinsic factor-cyano[57Co]cobalamin complexes exhibited comparable association constants for ileal receptors in canine brush-border vesicles, while there was minimal binding to jejunal vesicles. These findings demonstrate that the canine pancreas is an important source of an intrinsic factor that closely resembles gastric intrinsic factor in the dog. PMID- 2923216 TI - Migrating myoelectric complex demonstrated in four avian species. AB - The migrating myoelectric complex (MMC) is demonstrated in four avian species: three gallinaceous birds (Gallus, Phasianus, Coturnix) and an owl (Strix). The complex in birds is strikingly similar to the MMC that is known in mammalian species. It has the same basic pattern of quiescence, followed by a period of irregular spike activity, then a period of intense regular spike activity, and finally a return to quiescence. The frequency and duration of avian MMCs are similar to those of mammals, but the propagation velocity and slow-wave frequency are slower. Granivorous birds (Gallus, Phasianus) and carnivores (Strix) exhibit the same basic motility patterns whether in the fed or fasted states. Interspecific differences occur, however, in the details of frequency, propagation velocity, duration, and slow-wave frequency. The closely related galliforms (chickens, pheasants) are more similar to each other in MMC characteristics than either is to the more distantly related owls. PMID- 2923215 TI - Different mechanisms of contraction generation in circular muscle of canine colon. AB - Smooth muscle cells from the circular muscle layer of the dog colon showed a mechanical threshold of -44 mV. No gradient in mechanical threshold was measured between the cells from the submucosal and myenteric plexus surface. The threshold was passed during the upstroke and the plateau phase of the spontaneous slow-wave activity from cells at the submucosal surface and by spike potentials occurring mainly in cells at the myenteric plexus surface and sporadically in cells at the submucosal surface. Carbachol-induced specific changes in electrical and mechanical activities that were inhibited by calcium influx blockade are as follows: 1) increase in slow-wave duration; 2) decrease in plateau potential; 3) enhancement of spiking activity; and 4) increase in contractility. This indicates that calcium influx is significantly increased in the presence of carbachol in cells at both surfaces of the circular muscle layer. The increase in calcium influx could be the result of a direct action by carbachol on the calcium conductance and/or could be mediated by a decrease in outward current. The latter is suggested by the carbachol-induced membrane depolarization associated with an increase in the input resistance, which were both methoxyverapamil insensitive. The results show that an excitatory stimulus can generate contraction of the circular muscle through different electrophysiological activities. In addition, the patterns of spontaneous electrical activity and the different responses to carbachol stimulation provide further information about the heterogeneous nature of the electrical activities within the colonic circular muscle layer. PMID- 2923218 TI - D-glucose and L-leucine transport by human intestinal brush-border membrane vesicles. AB - This study utilized intestinal brush-border membrane vesicles obtained from organ donor intestine to characterize the absorption of D-glucose and L-leucine in the human intestine. Both D-glucose and L-leucine were taken up by sodium gradient dependent active transport along the entire length of the small intestine. The relative magnitude of transport for both substrates under sodium gradient conditions followed the order distal jejunum greater than proximal jejunum greater than distal ileum. The number of carrier systems in these brush-border membrane vesicles was estimated by Eadie-Hofstee plot analysis. This analysis revealed that L-leucine was actively transported via a single high-affinity transport system for the length of the human small intestine. In contrast, the transport of D-glucose occurred via a high-affinity system along the length of the intestine and via a low-affinity, high-flux transport system that was limited to the proximal intestine. Both glucose transport systems were sodium dependent and phlorizin sensitive. The locations and apparent kinetic parameters of these transport systems indicated that these systems function efficiently in vivo as important mechanisms for carbohydrate and protein assimilation in humans. The presence of these active transport systems along the entire small intestine explains the formidable capacity for carbohydrate and protein assimilation in humans. PMID- 2923217 TI - Effects of 1,25(OH)2D3 on enterocyte basolateral membrane Ca transport in rats. AB - One, twenty-five dihydroxyvitamin D3 [1,25(OH)2D3], commonly known as calcitriol, stimulates intestinal Ca absorption through increased activity of a cellular transport process. To determine whether transcellular Ca transport involves energy-dependent Ca efflux across enterocyte plasma membrane in vitamin D sufficient rats, in vitro bidirectional Ca fluxes were measured under short circuited conditions across proximal duodenum from rats fed diets adequate in vitamin D and containing a normal Ca diet (NCD), a low Ca diet (LCD), or fed NCD and injected with 50 ng of 1,25(OH)2D3 daily for 4 days before study. LCD or 1,25(OH)2D3 increased Ca net flux [Jnet, mucosal-to-serosal flux minus the serosal-to-mucosal flux] by increasing Ca mucosal-to-serosal flux (Jm----s) (mean +/- SE, NCD vs. LCD vs. 1,25(OH)2D3, 16 +/- 4 vs. 179 +/- 18 vs. 82 +/- 21 nmol.cm-2. h-1, P less than 0.0001). Initial ATP-dependent Ca uptake rates by duodenal basolateral membrane vesicles (BLMV) was greater in vesicles from rats fed NCD compared with LCD and not different from NCD injected with 1,25(OH)2D3. These studies suggest that in vitamin D-replete animals, 1,25(OH)2D3 increases epithelial Ca Jm----s by mechanisms that do not involve ATP-dependent BLM Ca efflux. ATP-dependent Ca exit from the cell under these conditions may play a role in intracellular Ca homeostasis rather than Ca absorption. PMID- 2923219 TI - Effect of dietary K+ and 75% nephrectomy on the morphology of principal cells in CCDs. AB - This investigation was carried out to determine the effect of potassium on the amplification of the basolateral membrane of principal cells in cortical collecting ducts (CCDs), which normally occurs after a large reduction of renal mass. Rats that underwent a 75% reduction of renal mass and were fed a diet deficient in potassium for 10 days after surgery had a lower concentration of potassium in the blood and excreted less potassium in the urine than either corresponding sham-operated (SO) rats or 75% nephrectomized (NPX) rats fed a normal-potassium diet. In the NPX rats fed the diet deficient in potassium, there was a marked inhibitory effect on the amplification of the basolateral membrane, which normally occurs in principal cells of CCDs after renal mass has been greatly reduced. In fact the surface density of the basolateral membrane, as well as the size of the principal cells in the animals fed the diet deficient in potassium were the same as those of principal cells in the SO rats fed the normal potassium diet. Thus the present data show that the increase in cell size and the amplification of the basolateral membrane that occurs in principal cells after a 75% reduction of renal mass is inhibited by factors associated with potassium depletion. PMID- 2923220 TI - Volume and ion transport by fetal rat alveolar and tracheal epithelia in submersion culture. AB - The complex architecture of the mammalian lung has hindered measurements of permeability of and transport by the intact alveolar epithelium. We compared properties of fetal rat alveolar buds and tracheas in submersion culture by microelectrode and micropuncture techniques. Both alveolar buds and tracheas form cysts that accumulate liquid for up to 3 wk in culture. The transepithelial electric potential difference (PD) of alveolar buds and tracheas (lumen negative, 1.2-3.5 and 8-21 mV, respectively) was abolished by metabolic inhibitors or ouabain in the bath. Despite the difference in PDs, both epithelial regions, after 1 or 2 wk in culture, exhibited the following. 1) Cl- activities and concentrations in luminal liquid were 13 and 34% higher than the bathing medium; Na+ and K+ concentrations were not different. 2) Bumetanide inhibited PD by 70%, whereas terbutaline increased PD by 45%. 3) Amiloride injected into the cyst lumen induced a 20% decrease in the PD of 1-wk explants but did not affect 2-wk preparations. Replacement of bath Na+ by choline decreased the PD of tracheas by 85% but did not change alveolar PD in the presence or absence of bumetanide. The pattern of cyst liquid composition and PD responses to drugs suggests that fetal rat alveolar and tracheal epithelia secrete Cl-, which drives volume flow. PMID- 2923221 TI - Interaction between loop of Henle flow and arterial pressure as determinants of glomerular pressure. AB - Experiments were performed in anesthetized rats to study the relationship between loop of Henle perfusion rate, arterial pressure, and stop-flow pressure (SFP) as an index of glomerular capillary pressure. In one set of experiments we measured the SFP feedback response to changes in loop perfusion at three levels of arterial pressure. The maximum SFP response fell significantly from 13.1 +/- 1.44 to 8.14 +/- 1.72 and 3.13 +/- 0.76 mmHg when arterial pressure was reduced from 118.1 +/- 1.27 to 98.8 +/- 0.51 and 78.8 +/- 1.72 mmHg. In other experiments arterial pressure was altered while loop perfusion rate was fixed at one of three levels. Without loop perfusion SFP changed with a slope of 0.27 +/- 0.04 mmHg/mmHg in the arterial pressure range between 80 and 130 mmHg. During perfusion at the flow rate at which response is half maximum, the slope was significantly reduced to 0.12 +/- 0.04. During perfusion at 45 nl/min, it was 0.03 +/- 0.05, a value not significantly different from zero. During dopamine administration (70 micrograms/kg min) SFP was pressure-dependent even during loop perfusion at 45 nl/min. These results show that arterial pressure determines TGF responsiveness and that the TGF signal determines the range of a regulatory input that is directly dependent on arterial pressure. PMID- 2923222 TI - Ketoacid production in acute respiratory and metabolic acidosis and alkalosis in rats. AB - Metabolic acidosis inhibits and alkalosis enhances ketoacid production in ketotic humans and animals. To compare these effects with those of superimposed respiratory acid-base disturbances, ketone output was evaluated in awake ketotic rats during metabolic (intravenous infusions of HCl or NaHCO3) or respiratory (hyper or hypocapnia) disorders. With decreases in blood pH of 0.1-0.2 units over 3 h, blood ketone concentrations significantly decreased an average of 1.9 mM (metabolic) and 1.1 mM (respiratory) and urinary ketone excretion rates significantly decreased by 1.3 mumol/min (metabolic). With increases in systemic pH, blood ketone concentrations and urinary ketone excretion rates were significantly increased. Changes in blood pH correlated with changes in urinary ketone excretion rates in both metabolic (r = 0.87) and respiratory (r = 0.67) acid-base disturbances. The alterations occurred promptly and were rapidly reversible. These findings indicate that modest changes in systemic pH from metabolic or respiratory acid-base disturbances modify net ketoacid production in ketotic rats, confirm pH control of endogenous acid output as an acid-base regulator, and show that systemic pH, not bicarbonate concentration, mediates the process. PMID- 2923223 TI - Pathogenetic mechanisms in experimental hemoglobinuric acute renal failure. AB - To evaluate mechanisms in hemoglobinuric acute renal failure (ARF) rats were infused with hemoglobin under aciduric or alkalinuric conditions. Aciduric rats developed azotemia, distal heme casts, and proximal tubular cell (PTC) necrosis, whereas alkalinuric rats developed no renal damage. Aciduria converted hemoglobin to met-hemoglobin, which precipitated, forming distal casts and inducing ARF. Hematin formation was not observed. The importance of met-hemoglobin production was indicated by its greater toxicity than hemoglobin during aciduria and by its ability to induce ARF even under alkalinuric conditions. A link between obstructing casts and PTC necrosis was identified; tubular obstruction induced by various mechanisms (met-hemoglobin casts; ureteral ligation; ischemic ARF) increased PTC hemoglobin uptake, producing lysosomal overload (giant endolysosomes) and PTC necrosis. This worsened ischemic ARF despite an otherwise subtoxic hemoglobin dose being used that had no discernible acute renal vasoconstrictive effect. Iron chelation (deferoxamine)/hydroxyl radical scavenger (Na benzoate) therapy did not mitigate this exacerbation of ischemic injury, suggesting a nonoxidant mechanism. We conclude that H is nephrotoxic, particularly when intratubular obstruction facilitates PTC heme uptake. Thus aciduria-induced met-hemoglobin cast formation and concomitant ischemic renal injury predispose to its nephrotoxic effect. PMID- 2923224 TI - Inner medullary blood flow in postischemic acute renal failure in the rat. AB - To study the effect of renal ischemia on the circulation in the inner medulla, blood flow in descending and ascending vasa recta was determined by fluorescence videomicroscopy in the exposed papilla of the uninephrectomized rat after clamping of the renal artery for 45 min. Total renal blood flow was determined in parallel studies with an electromagnetic flowmeter. Animals were studied 90 min (group 1E) and 24 h (group 2E) after right nephrectomy and release of the left renal artery clamp. Control rats were studied 90 min (group 1C) and 24 h (group 2C) after right nephrectomy alone. In groups 1E and 2E, total renal blood flow was reduced to 70 and 80% of that in their respective controls; renal vascular resistance increased by 50 and 73%, respectively. In striking contrast, blood flow was markedly elevated in descending and ascending vasa recta in groups 1E and 2E compared with the values in their respective uninephrectomized controls. These results indicate that the circulation in the inner medulla is rapidly restored after 45 min of total renal ischemia and that vasa recta blood flow rises above normal after 90 min and 24 h, despite a reduction in total renal blood flow and an increase in renal vascular resistance. PMID- 2923225 TI - Amiloride transport in rabbit renal brush-border membrane vesicles. AB - Rabbit renal brush-border membrane vesicles (BBMV) were used to study amiloride transport across the luminal membrane of proximal tubular cells. An outwardly directed H+ gradient (pHi 6.0; pHo 7.5) stimulated 8 microM [14C]-amiloride uptake into BBMV and supported a transient "active" accumulation of substrate consistent with the presence of an amiloride-H+ exchange process. Uptake was inhibited, in the presence or absence of a pH gradient, by 1 mM unlabeled amiloride or 20 mM tetraethylammonium (TEA). Amiloride transport was not directly affected by the presence of 100 mM Na+ in the extravesicular medium, suggesting that Na-H exchange did not mediate amiloride flux. Amiloride transport was a saturable process with a maximal flux (under pH gradient conditions) of 3 nmol.mg 1.min-1 and an apparent Kt of 8 microM. TEA acted as a competitive inhibitor of this process with an apparent Ki of approximately 80 microM, similar to the Kt of TEA transport via the TEA-H+ exchanger. Likewise, amiloride acted as a competitive inhibitor of TEA uptake with an apparent Ki of approximately 11 microM. Preloading BBMV with 1-2 mM TEA stimulated the rate of amiloride uptake and supported a transient active accumulation of amiloride. We conclude that amiloride and TEA are transported by a common pathway in BBMV, which involves a carrier-mediated exchange with H+ and which may play a role in the tubular secretion of these compounds. PMID- 2923226 TI - Voltage dependence and barium sensitivity of colonic K secretion in renal failure. AB - Net colonic K secretion (JKnet) is increased in rats and humans with chronic renal failure (CRF). To study whether transepithelial potential difference (PD), active transport forces and/or luminal K conductance play a role in this adaptation, experiments were performed in the colon of control, K-adapted, and CRF rats. Under basal conditions the PD in vivo in CRF was greater than in controls and not different from K-adapted rats. JKnet was comparable in vivo in CRF and K-adapted rats and was greater than in controls. Amiloride (10 microM) reduced PD and JKnet in K-adapted and CRF rats to levels comparable to controls. Under in vitro short-circuited conditions serosal-to-mucosal K flux (JKs----m) in distal colon was significantly increased in K-adapted and CRF animals compared with control, whereas barium caused a significant reduction in JKs----m in all groups of animals. The barium-sensitive component of K secretion was greater, however, in the two experimental groups (-0.2 +/- 0.02 and -0.2 +/- 0.07 in K adapted and CRF animals, respectively, vs. -0.08 +/- 0.02 microeq.h-1.cm-2 in controls, P less than 0.05). However, luminal barium failed to completely inhibit the increase in K secretion observed in the experimental groups. These data suggest that an increase in PD that results in a rise in luminal negativity, stimulation of active transport, and an increase in barium-sensitive K channels and barium-insensitive pathways in apical membrane of distal colon participate in the mechanism by which net K secretion is increased in the large intestine of subjects with CRF. PMID- 2923227 TI - Effect of inosine on pial arterioles: potentiation of adenosine-induced vasodilation. AB - We examined the cerebral vasoactivity of inosine and its effect on pial arteriolar vasodilation induced by adenosine. Pial circulation was observed through cranial windows implanted in rats anesthetized with halothane. No significant change in venous or arteriolar diameter was apparent when inosine (10(-6) to 10(-3) M) was superfused. In contrast, adenosine in concentrations of 10(-7) and 10(-6) M dilated pial arterioles by 9.0 +/- 1.2 and 17.7 +/- 1.7%, respectively. Addition of 10(-5) M inosine had no effect, whereas 10(-4) M inosine enhanced the vasodilation induced by 10(-7) M adenosine to 19.4 +/- 1.7% and that by 10(-6) M adenosine to 23.3 +/- 2.3%. When theophylline (5 X 10(-5) M) was perfused together with 10(-7) M adenosine and 10(-4) M inosine, the vasodilation was almost completely abolished. The present study indicates that inosine alone does not affect pial vessel diameter but potentiates the response of pial arterioles to exogenous adenosine. This potentiating action of inosine may be attributed to an increase in perivascular adenosine and may be explained by the action of inosine as an adenosine uptake inhibitor. PMID- 2923228 TI - Adrenergic control of intrarenal arteries of rabbits. AB - A comparative study of the adrenergic control of two sequential rabbit intrarenal arteries of differing diameter [intrarenal branch artery (IRBA)-unstretched lumen diameter (ULD) approximately 300 microns and interlobar artery (ILA)-ULD approximately 250 microns] has been conducted. The neurogenic contractile response of isolated segments in relation to the maximum response to l norepinephrine (NE) was minimal (8 Hz response approximately 30% of maximum contraction) and similar in both types of arteries. Phentolamine (PTA) (10(-6) M) blocked neurally evoked contractions of the IRBAs at 2, 4, and 8 Hz and of the ILAs at 2 and 4 Hz. (8 Hz responses were not entirely blocked in 3 out of 8 ILAs.) The sensitivity to exogenous NE decreased with a decrease in intrarenal vessel diameter, whereas the maximum active smooth muscle cell stress to NE was greater than 3 X 10(5) N/m2 for each vessel. All arterial segments constricted in response to histamine (H) and NE with equal maximal effects; however, sensitivity to H was greater in the smaller artery (ILA). The comparative contractile responses to nerve stimulation and exogenous NE in sequential renal arteries contrasts to the pattern of these responses in sequential arteries in any other rabbit regional bed previously studied (pulmonary and ear vasculature). PMID- 2923229 TI - Responses to acute hypoxemia in fetal sheep at 0.6-0.7 gestation. AB - A majority of previous studies of fetal responses to acute hypoxemia has focused on the response of the sheep fetus greater than 120 days of gestation when many regulatory systems have been established. To assess the response of younger, less well-developed fetuses, we exposed two groups of fetal sheep (I, 84-91 days; II, 97-99 days gestational age) to acute hypoxemia by giving the ewe a gas mixture containing 9% O2 to breathe. We decreased descending aortic PO2 in both groups of fetuses [I, 24 +/- 6 to 14 +/- 3 (SD) Torr; II, 23 +/- 3 to 12 +/- 4 Torr] by a degree similar to that achieved in previous studies of fetuses greater than 120 days of gestation. Mean arterial blood pressure (I, 31 +/- 6; II, 40 +/- 3 Torr) did not change significantly from control values, and heart rate (I, 224 +/- 27; II, 203 +/- 16 beats/min) increased significantly in group II fetuses with hypoxemia. In group I and II fetuses, as in older fetuses, cerebral, myocardial, and adrenal blood flows, measured by the microsphere technique, increased, and pulmonary blood flow decreased. These responses mature early and are likely local vascular responses to decreases in oxygen content. Combined ventricular output and umbilical-placental blood flow decreased significantly in both groups. Unlike the response of the fetus greater than 120 days, acute hypoxemia did not decrease blood flow to the musculoskeletal and cutaneous circulations (group I only), gastrointestinal, or renal circulations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2923230 TI - Impairment of endothelium-dependent dilatation of cerebral arterioles during diabetes mellitus. AB - The goal of this study was to determine whether responses of cerebral arterioles to vasoactive substances released by platelets are altered during diabetes mellitus. To induce diabetes, rats were injected with streptozotocin (50-60 mg/kg ip). Rats were characterized as diabetic by a blood glucose of greater than 300 mg/dl. Diameter of pial arterioles was measured during superfusion with ADP, serotonin, and the thromboxane analogue (U-46619), with the use of intravital microscopy in control (non-diabetic) and diabetic rats. ADP (10(-5)M) increased pial arteriolar diameter by 13 +/- 1% (mean +/- SE) in control rats and did not change diameter of arterioles in diabetic rats (1 +/- 1%). Serotonin (10(-5)M) increased diameter of cerebral arterioles by 9 +/- 1% in control rats and constricted arterioles by 5 +/- 2% in diabetic rats. Nitroglycerin produced similar dilatation of cerebral arterioles in control and diabetic rats, suggesting that impaired dilatation of cerebral arterioles in diabetic rats was not related to nonspecific impairment of vasodilatation. The thromboxane analogue U-46619 produced similar constriction of cerebral arterioles in control and diabetic rats. Thus endothelium-dependent dilatation of cerebral arterioles in response to ADP and serotonin is profoundly impaired in diabetic rats. PMID- 2923231 TI - Length-tension relationship of vascular smooth muscle in single arterioles. AB - Longitudinal response gradients in the microcirculation may in part be explained in terms of the length-tension relationship of vascular smooth muscle at different points along the vascular tree. To test this hypothesis, four branching orders of arterial vessels (20-80 microns ID) were dissected from the hamster cheek pouch and cannulated with concentric micropipettes. Intraluminal pressure was monitored with a servo-null micropipette, and arteriolar dimensions were measured using a videomicrometer. All arterioles developed spontaneous tone in physiological saline solution. Pressure-diameter curves were recorded for maximally activated vessels and for passive vessels. Maximal active wall tension varied nearly threefold, but maximal active medial wall stress (approximately 4 x 10(6) dyn/cm2) varied only approximately 20% between the different vessel orders. These data support the concept that smooth muscle cells from vessels of different sizes are mechanically similar but do not completely explain the longitudinal response gradients reported in the cheek pouch microcirculation. An analysis of the effect of arteriolar wall buckling suggests that the luminal folds that develop at short vessel radii may broaden the peak of the active stress-length curve and extend the pressure range over which arterioles are most sensitive to physical and chemical stimuli. PMID- 2923233 TI - Effect of myocardial ischemia on hemodynamic response to carotid occlusion. AB - Fourteen mongrel dogs were anesthetized and instrumented to measure arterial pressure (AP), left ventricular pressure (LVP), aortic blood flow, and heart rate (HR). Hydraulic occluders were placed around the left anterior descending (LAD, n = 9) and left circumflex (LCC, n = 14) coronary arteries. A bilateral carotid occlusion (BCO) was made before and during either anterior (LAD occlusion) or posterior (LCC occlusion) ischemia. Posterior ischemia significantly (P less than 0.01) reduced the BCO-induced increases in mean AP (by 44.3 +/- 7.3%), systolic LVP (by 65.5 +/- 6.9%), first derivative of LVP (dLVP/dt, by 95.7 +/- 44.3%), and aortic resistance (by 117.7 +/- 26.9%). In contrast, anterior ischemia failed to alter significantly the hemodynamic response to BCO. Bilateral vagotomy attenuated or eliminated many of the effects of posterior ischemia on the BCO response. In fact, the change in aortic resistance was no longer affected by the ischemia and increased to the same extent, as noted during the control BCO. However, mean AP (38.7 +/- 6.8%), systolic LVP (40.3 +/- 8.7%), and dLVP/dt (62.4 +/- 11.0%) remained significantly reduced when compared with the control (no coronary occlusion) response. These data suggest that 1) posterior ischemia elicits a greater reduction in the BCO response than anterior ischemia, and 2) vagal afferents as well as depression of contractile function may both contribute to the BCO response inhibition noted during posterior ischemia. PMID- 2923232 TI - Effects of arginine vasopressin on hemodynamics and lung fluid balance in lambs. AB - The purpose of this project was to study the effects of increased plasma concentrations of arginine vasopressin (AVP) on hemodynamics and lung fluid balance in lambs. We studied 16 unanesthetized newborn lambs during a base-line period and while infusing AVP into a hindlimb vein at 1.65 +/- 0.12 and 2.98 +/- 0.15 mU.kg-1.min-1. We measured aortic, pulmonary arterial, and left atrial pressures and heart rate continuously and cardiac output at frequent intervals. In five additional experiments, we collected samples of pure lung lymph during a base-line period and while infusing AVP at 2.02 +/- 0.15 mU.kg-1.min-1. AVP infusion increased plasma concentrations of AVP to 11.3 +/- 5.2 and 19.9 +/- 5.2 microU/ml at the low and high rates of infusion, respectively. Both aortic and left atrial pressures increased at the low rate of infusion (11 and 3 Torr, respectively) but remained unchanged at the higher rate. Systemic vascular resistance increased, and heart rate and cardiac output decreased at each rate of infusion. In fact, at the higher rate of infusion cardiac output decreased 38% when compared with base line. Neither pulmonary artery pressure nor pulmonary vascular resistance was affected by infusion of AVP. Despite the increase in left atrial pressure, the rate of lung lymph flow was not affected by the infusion of AVP, whereas the lymph-to-plasma protein ratio decreased slightly but significantly from 0.64 +/- 0.02 to 0.60 +/- 0.02.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2923234 TI - Deleterious effect of ouabain on myocardial function during hypoxia. AB - The effect of cardiac glycosides on myocardial function during hypoxia is controversial. Accordingly, we studied left ventricular performance during hypoxia and reoxygenation in the presence of a mildly inotropic, nontoxic dose of ouabain using isolated, isovolumic, buffer-perfused rabbit hearts. After 15 min of hypoxia, left ventricular developed pressure was less in the ouabain-treated group than in controls (35 +/- 4 vs. 55 +/- 3 mmHg, P less than 0.025). Left ventricular end-diastolic pressure (LVEDP) increased more during hypoxia in the presence of ouabain (9 +/- 1 to 32 +/- 7 with ouabain vs. 9 +/- 1 to 14 +/- 3 mmHg without ouabain, P less than 0.005) despite comparable degrees of coronary vasodilatation and myocardial lactate production in the two groups. When coronary flow was abruptly reduced to zero to eliminate the coronary turgor contribution to diastolic pressure, LVEDP after 15 min of hypoxia in the presence of ouabain was greater than that in control hearts that did not receive ouabain (13 +/- 4 vs. 4 +/- 1 mmHg, P less than 0.05), implicating greater diastolic myocardial fiber tension in the ouabain group during hypoxia. With reoxygenation, recovery of developed pressure was less and end-diastolic pressure remained elevated in the ouabain-treated group when compared with controls. We conclude that a modestly inotropic dose of ouabain exacerbates the decrease in diastolic ventricular distensibility induced by hypoxia, worsens the decline in developed pressure during hypoxia, and impairs recovery during reoxygenation. PMID- 2923235 TI - Coronary vascular responses to chemical stimulation of abdominal visceral organs. AB - Topical application of bradykinin or capsaicin to abdominal visceral organs produces adrenergically mediated, reflex increases in mean arterial pressure and cardiac work. To determine the effects on coronary blood flow, the left main coronary artery of anesthetized cats was perfused at constant pressure with a servo-controlled pump. Cardiovascular parameters were measured during reflex stimulation before and after beta-adrenoceptor blockade with propranolol. Before propranolol, reflex activation led to increases in the double product and myocardial oxygen consumption, usually accompanied by increases in coronary blood flow. However, in 32% of the observations, decreases in flow were observed. During beta-adrenoceptor blockade, reflex stimulation produced increases in cardiac work, whereas the increases in coronary blood flow were attenuated. Marked decreases in average coronary blood flow were observed more frequently (42%). In the presence of propranolol, contrary to the unblocked state, increases in oxygen consumption were achieved by increased oxygen extraction. Subsequent alpha-adrenoceptor blockade with phentolamine abolished all reflex changes. These data indicate that during stimulation of abdominal visceral chemoreceptors, the major coronary response is vasodilation, but in a sizable fraction of cases, abdominal visceral reflexes can produce sympathetically mediated coronary vasoconstriction. PMID- 2923236 TI - Effect of hematocrit on microvascular pressures in 3- to 5-wk-old rabbit lungs. AB - To examine the effects of blood hematocrit (Hct) and apparent viscosity on the pulmonary microcirculation, we studied 30 isolated, perfused 3- to 5-wk-old rabbits with varying perfusate Hct. We partitioned total vascular resistance by measuring pulmonary artery and left atrial pressures and by micropuncture the pressures in the subpleural microcirculation in 20-40 microns diameter arterioles, 20-40 microns venules, and 250-300 microns venules. To prevent active vasomotion and changes in vessel geometry, we paralyzed the vasculature with papaverine hydrochloride. We studied four groups of lungs: group I (n = 7) with low Hct (17.8 +/- 2.4%); group II (n = 9) with medium Hct (46.8 +/- 8.2%); group III (n = 6) with high Hct (74.4 +/- 5.8%); and group IV (n = 8) with both low and high Hct perfusates. Lungs were perfused at constant flow (80 +/- 4 ml.kg body wt 1.min-1) in zone 3, airway and venous pressures being 6 and 8 cmH2O, respectively. We found that in lungs perfused with low Hct, approximately 52% of the total resistance was in arteries, approximately 25% in microvessels, and approximately 21% in small veins, with very little resistance in large veins. With an increase in perfusate hematocrit and apparent viscosity, total pulmonary vascular resistance increased mainly because of an increase in resistance in arteries and small veins, with little change in resistance in microvessels and large veins. PMID- 2923237 TI - d-Propranolol prevents adenosine formation associated with myocardial hypoperfusion. AB - d-Propranolol eliminates the increased adenine nucleoside release from hypoperfused hearts [R. D. Wangler, D. F. DeWitt, and H. V. Sparks, Am. J. Physiol. 247 (Heart Circ. Physiol. 16): H330-H336, 1984]. To determine whether d propranolol reduces adenosine formation or adenosine release into the vascular compartment, we measured myocardial tissue adenosine (TADO). Decreased formation would lower TADO, whereas decreased release would elevate TADO. Reduction of perfusion pressure by 50% reduced coronary flow (CF), venous oxygen tension (PVO2), and myocardial oxygen consumption (MVO2) by approximately 40, 25, and 35%, respectively. Total adenosine and inosine released during 30 min of hypoperfusion increased 10- and 5-fold, respectively. Also, TADO increased from 2.68 +/- 0.37 to 5.17 +/- 0.67 nmol/g (P less than 0.05). In the presence of d propranolol, the same reduction in perfusion pressure caused a similar decrease in CF and MVO2. d-Propranolol eliminated the release of adenosine and inosine associated with hypoperfusion. TADO after 30 min of hypoperfusion plus d propranolol was not significantly increased (3.27 +/- 0.40 nmol/g) and was significantly less than hypoperfused hearts. When severe hypoperfusion was created by reducing perfusion pressure 75%, adenosine release still did not increase if d-propranolol was present. When adenosine release was plotted as a function of oxygen supply-consumption, they were related in a hyperbolic fashion. Despite the severity of hypoperfusion, in the presence of d-propranolol the supply-to-consumption ratio was similar to that of the control perfusion group (no drug). We conclude that d-propranolol blocks nucleoside formation during hypoperfusion by reducing oxygen demand such that a reduction of oxygen supply no longer stimulates adenosine formation. PMID- 2923238 TI - Cerebral blood flow and evoked potentials during Cushing response in sheep. AB - We determined how alterations in systemic hemodynamics, characteristic of the Cushing response, are related to changes in cerebral blood flow (CBF), cerebral metabolic rate of O2 (CMRO2), and brain electrical conductive function, as assessed by somatosensory-evoked potentials (SEP) and brain stem auditory-evoked responses (BAER). In three groups of eight pentobarbital-anesthetized sheep, intracranial pressure was gradually elevated to within 50, 25, or 0 mmHg of base line mean arterial pressure and then held constant for 40 min by intraventricular infusion of mock cerebrospinal fluid. Microsphere-determined CBF fell when cerebral perfusion pressure was less than 50 mmHg. CMRO2 fell when CBF fell greater than 30-40%. Mean aortic pressure and cardiac output increased when CBF fell greater than 40%, i.e., at approximately the level at which CMRO2 fell. Furthermore, the magnitude of the increase in arterial pressure and cardiac output correlated with the reduction of CMRO2. SEP latency did not increase unless CBF fell greater than 55-65%, corresponding to a 20-30% reduction of CMRO2. Increased latency of BAER wave V was associated with a fall in midbrain blood flow of greater than 65-70%. Thus increase in SEP and BAER latencies required reductions of flow greater than those required to elicit a systemic response. This demonstrates that there is a range of intracranial pressure over which the increase in arterial pressure preserves sufficient CBF to sustain minimal electrical conductive function. The best predictor of the onset and magnitude of the Cushing response in adult sheep is the decrease in CMRO2. PMID- 2923239 TI - Free radical defense mechanisms and neutrophil infiltration in postischemic skeletal muscle. AB - A growing body of experimental data indicates that reactive oxygen metabolites such as superoxide, hydrogen peroxide, and hydroxyl radicals may mediate the microvascular and parenchymal injury produced by reperfusion of ischemic skeletal muscle. One potential source of these reactive oxygen metabolites is the inflammatory neutrophil. To assess neutrophil accumulation in postischemic skeletal muscle, we measured tissue myeloperoxidase (MPO) activity in skeletal muscle biopsies taken during control, after 4 h of ischemia, and after 1 h of reperfusion. Tissue levels of reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) were measured in the same samples to identify alterations in tissue free radical defense mechanisms due to ischemia reperfusion. Reperfusion of ischemic skeletal muscle was associated with a dramatic increase in tissue neutrophil content (as reflected by a 26-fold increase over control in tissue MPO activity after 1 h of reperfusion) and a concurrent 50% decrease in GSH content. Tissue CAT and SOD activities were unaffected by ischemia-reperfusion. These results suggest a possible relationship between ischemia-reperfusion-induced injury, neutrophil infiltration, and the reduction in tissue GSH. PMID- 2923240 TI - Effect of umbilical blood flow on transplacental diffusion of ethanol and oxygen. AB - We studied the effect of varying umbilical blood flow (F) on transplacental diffusion of ethanol and O2 before and during partial occlusion of the fetal abdominal aorta. At steady state, samples of umbilical and uterine arterial and venous blood were drawn simultaneously from chronically indwelling catheters and analyzed for the concentration of ethanol. O2 capacity, O2 saturation, PO2, PCO2, and pH. A decrease in F from 507 to 289 ml/min (P less than 0.001) was associated with a significant (P less than 0.02) increase of the umbilical-uterine venous ethanol concentration difference. This increase was indicative of a 25% diffusional shunt for ethanol on the fetal side of the placenta. The decrease in F caused a decrease in the umbilical O2 delivery-to-control O2 uptake ratio from 3.1 to values between 2.2 and 0.8 and was associated with a decrease in fetal O2 uptake to values between 94 and 56% of control. Uterine venous PO2 increased in response to the decrease in fetal O2 uptake. Umbilical venous PO2 correlated with uterine venous PO2 (r = 0.8, P less than 0.02). The response of fetal O2 uptake to decrease in umbilical O2 delivery was nonlinear and confirmed previous studies, showing that the normal umbilical O2 delivery rate exceeds approximately twofold the minimum necessary to sustain a normal rate of fetal oxidative metabolism. PMID- 2923241 TI - Propagation of vasomotor responses coordinates arteriolar resistances. AB - We tested the hypothesis that a conduction pathway intrinsic to the arteriolar wall possesses the properties necessary to coordinate vasomotor responses in the microcirculation. Acetylcholine (ACh) or norepinephrine (NE) was iontophoresed onto cheek pouch arterioles (15-35 microns diam) of pentobarbital-anesthetized hamsters, and diameter responses were observed using intravital video microscopy. ACh and NE induced vasodilation and vasoconstriction, respectively, that propagated both upstream and downstream from the site of application. Propagated vasomotor responses decayed with distance along the arterioles; this decay was characterized by mechanical length constants of 1.9 and 1.8 mm for ACh and NE, respectively. Vasodilations and vasoconstrictions initiated on daughter vessels of a branch propagated into parent arterioles that were approximately twice the diameter of the daughter vessels. Iontophoretic stimuli applied simultaneously to paired daughter vessels induced propagated responses that summed linearly in the parent vessel. We conclude that the arteriolar network functions as a highly coordinated syncytium and that diverse vasomotor stimuli can be summed and integrated within the peripheral microvasculature. PMID- 2923242 TI - Conduction of vasomotor responses in arterioles: a role for cell-to-cell coupling? AB - Vasomotor responses of arterioles triggered by the iontophoretic application of acetylcholine (ACh) or norepinephrine (NE) are conducted along the vessel wall. The present experiments focus on elucidating the mechanism of conduction in arterioles of the superfused cheek pouch preparation in pentobarbital anesthetized hamsters. Localized muscarinic or adrenergic receptor blockade on an arteriolar segment produced by atropine or phentolamine, respectively, did not affect propagation through the region of blockade but did block vasomotor responses to ACh or NE applied to the segment. Thus muscarinic and alpha adrenergic receptors can trigger the propagation of vasomotor responses, but these receptors are not involved in their conduction. Tetrodotoxin did not affect either local or propagated responses to ACh or NE. Treatment of arteriolar segments with calcium antagonists (verapamil, diltiazem, nifedipine, or manganese) caused maximal dilation locally but did not affect propagation through the dilated region. The preceding findings argue against a neural pathway for propagation. A depolarizing solution (137 mM KCl) applied by micropipette to arteriolar segments caused both local and propagated vasoconstriction and significantly attenuated propagated vasodilation induced with ACh (P less than 0.05). Putative antagonists of gap-junctional communication (hypertonic sucrose solution, octanol, CO2) reversibly attenuated or abolished propagated responses. We hypothesize that propagation of vasomotor responses along arterioles is initiated via a local change in membrane potential secondary to receptor occupation and that changes in potential spread electrotonically through gap junctions coupling smooth muscle cells, endothelial cells, or both. PMID- 2923243 TI - Basal metabolic energy requirements of polarized and depolarized arrest in rat heart. AB - Basal energy requirements of polarized [tetrodotoxin (TTX), 25 microns] and depolarized [potassium (K), 20 mM] arrested hearts were studied by continuously measuring myocardial oxygen consumption (MVO2) during 60 min of normothermic arrest in isolated Langendorff-perfused rat hearts. TTX, a fast sodium channel blocker, was used to produce polarized arrest because of its specificity and reversibility. MVO2 was significantly lower in the polarized (TTX) group at all time points, a typical difference occurring 30 min after arrest (0.070 +/- 0.005 vs. 0.109 +/- 0.006 ml O2.min-1.g dry wt-1, P less than 0.001). Coronary flow was lower in the polarized group (14.3 +/- 1.4 vs. 28.4 +/- 2.2 ml.min-1.g dry wt-1, P less than 0.001, data at 30 min of arrest), but flow-restricted studies showed basal MVO2 to be independent of variation in coronary flow within this range. Recovery of function was similar in both groups. Ventricular pressure during cardiac arrest was lower in the polarized group (5.5 +/- 1.2 vs. 10.3 +/- 1.3 mmHg, P less than 0.01, data at 30 min of arrest), implying reduced myocardial wall tension and a lower intracellular calcium concentration. These results suggest that polarized arrest can decrease myocardial metabolic demands below that of depolarized arrest. A plausible mechanism is a reduction in myocardial wall tension caused by decreased calcium influx mediated by the Na-Ca exchanger. PMID- 2923244 TI - Subendocardial infarction produces epicardial parasympathetic denervation in canine left ventricle. AB - Forty dogs underwent anterior descending coronary artery dissection with most having occlusion that was either maintained or reperfused. Study was performed 1 4 days later. Multiple electrodes placed in normal and ischemic zones were used to determine the depth of the epicardial rim overlying a subendocardial infarction. This was done by comparing voltage differential with respect to time (dV/dt) measurements of sequential bipolar electrograms along each needle. By this means, test sites with a rim were documented, and depths of epicardial biopsies for choline acetyltransferase were chosen. Epicardial effective refractory period (ERP) responses to vagal nerve stimulation were measured. In sham-operated controls, vagal stimulation prolonged ERP, and choline acetyltransferase activity was equivalent in all sites. In contrast, dogs with all durations of coronary occlusion and various thicknesses of subendocardial infarction had no significant prolongation of ERP limited to rim sites overlying the infarct during vagal nerve stimulation. Corresponding choline acetyltransferase activity was decreased in rim sites compared with remote areas. In addition, dogs given norepinephrine or physostigmine (to potentiate parasympathetic responses) did not demonstrate significant ERP prolongation with vagal stimulation. Infusion of acetylcholine into the distal ligated coronary artery produced dose-dependent prolongation of ERP in sites overlying the infarct. These data taken together support the hypothesis that subendocardial infarction, regardless of its homogeneity or thickness, produces parasympathetic denervation of the overlying epicardial rim. PMID- 2923245 TI - Mutual interaction of vasoconstriction and endothelial damage in stenotic arteries. AB - Coronary artery vasomotion may be important in the pathogenesis of angina pectoris. Numerous experimental studies demonstrated accentuated arterial vasomotion in endothelium-damaged vessels. We examined interactions of stenosis, arterial vasoconstriction, and endothelium denudation in a stenosed artery preparation in vitro. Canine carotid arteries and porcine coronary arteries were perfused with a physiological salt solution under constant pressure and a fixed distal resistance. Pressures at the proximal and distal ends of the artery, as well as the flow, were continuously recorded. Hemodynamic responses to serotonin, norepinephrine, and angiotensin II were separately studied. In intact arteries without stenosis, the agonists produced a 30-40% reduction in lumen diameter without altering flow or distal pressure. After a luminal stenosis was created, vasoconstriction produced by the agonists decreased flow and increased the pressure gradient across the stenosis. Flow decreased to (or near) zero, indicating occlusion at the stenotic site. After endothelial loss, this effect was amplified, demonstrating occlusion of the artery and suppression of the flow at significantly (P less than 0.05) lower concentrations of agonist (0.1-0.3) compared with endothelial intact arteries. These studies illustrate 1) the necessity for the presence of stenosis in large arteries for vasoconstriction to impair flow and 2) the protecting effect of intact endothelium in blunting the effects of arterial vasoconstriction in stenosed vessels. Through the reciprocal interaction of arterial stenosis, vasoconstriction, and endothelial damage, ischemic events associated with certain types of vasomotion can be explained. PMID- 2923246 TI - Coronary sinus pressure and arterial flow during intermittent coronary sinus occlusion. AB - The relationship between coronary artery flow and coronary venous pressure during intermittent coronary sinus occlusion was studied in dogs at normal perfusion, left anterior descending artery occlusion, and reperfusion. Coronary sinus occlusion and release phases were varied systematically. The periodicity of the data and the assumption of a linear relationship between pressure and flow suggested Fourier analysis as a methodological approach. To show the systematic slow oscillations of coronary venous pressure and arterial flow induced by intermittent occlusion of the coronary sinus, the data were smoothed by superimposing consecutive cycles of identical occlusion-release timing and filtering the higher frequencies. A small number of Fourier components, corresponding to the time scale of the respective occlusion-release cycle, was sufficient to study the long wavelength behavior. The effect of arbitrarily varying the occlusion-to-release ratio at a given total cycle length was investigated in hypothetical pressure and flow curves based on interpolation of experimental Fourier coefficients. By means of a transfer function relating pressure and flow in the frequency domain, it was possible to predict the arterial flow curve using coronary venous pressure measurements only. Because at zero frequency the pressure-flow relationship cannot be assumed to be linear, the mean value of flow could not be obtained in this way. However, the deviation of flow from the mean, i.e., the shape of the flow curve, was reproduced satisfactorily. PMID- 2923247 TI - Rate of oxygen loss from arterioles is an order of magnitude higher than expected. AB - The experimental data on oxygen flux from arterioles in the hamster cheek pouch retractor muscle [L. Kuo and R. N. Pittman, Am. J. Physiol. 254 (Heart Circ. Physiol. 23): H331-H339, 1988] were analyzed under the assumption that the permeability to oxygen is the same in both perfused and unperfused tissue; permeability is defined as the product of the diffusion and solubility coefficients. However, our analysis indicated that the observed oxygen flux was inconsistent with this assumption and that permeability to oxygen of a blood perfused tissue may be an order of magnitude higher than previously assumed. PMID- 2923248 TI - Pulse-synchronized contractions: and addendum to Windkessel. PMID- 2923249 TI - Fourth ventricle bombesin injection suppresses ingestive behaviors in rats. AB - Food intake after fourth intracerebroventricular (icv) injections of bombesin (BBS) was measured in intact rats. BBS injections (greater than or equal to 10 ng) reliably suppressed chow intake in 17-h food-deprived rats. Systemic injections of BBS (50 ng) had no effect on food intake. These data indicate that BBS can act directly on caudal brain stem site(s) to inhibit food intake. The behavioral specificity of fourth icv BBS was evaluated by measuring the effects of fourth icv BBS injection on water intake by 17-h water-deprived rats in the presence and absence of food. Fourth icv injections of BBS in doses greater than 10 ng suppressed 30-min and 2-h water intake relative to saline injection when food was available in the home cage. In contrast, when food was not present during the 2-h intake test, fourth icv injections of BBS had no effect on water intake. This suggests that the inhibition of water intake was secondary to the effects of BBS on food intake. Lastly, sucrose (0.1 M) was paired with fourth icv BBS (50 ng), fourth icv saline, and intraperitoneal LiCl (1.5 meq/kg) in three groups of naive rats, and sucrose preference was subsequently measured. Rats that received injections of either saline or BBS preferred sucrose during the 24-h two bottle test, and their preference ratios were significantly greater than those of the LiCl-injected rats. The role of afferent signals elicited by fourth ventricle BBS administration in the control of food intake is discussed. PMID- 2923250 TI - Effect of blood glucose concentration on osmoregulation in diabetes mellitus. AB - Poorly controlled insulin-dependent diabetes mellitus is associated with considerable elevations of plasma vasopressin concentrations, although well controlled diabetics have normal osmoregulated thirst and vasopressin release. We studied the effect of blood glucose concentration on osmoregulated thirst and vasopressin secretion in insulin-dependent diabetes mellitus. Blood glucose was maintained overnight, and for the duration of the study, in either the euglycemic (4-5 mmol/l) or hyperglycemic (10-12 mmol/l) range, and patients underwent infusion of hypertonic (855 mmol/l) sodium chloride solution. Plasma sodium was lower during the hyperglycemic study, but elevation in plasma sodium concentration by infusion of saline caused progressive linear increases in both thirst and plasma vasopressin concentrations in both studies. Linear regression analysis defined lowered plasma sodium thresholds for both thirst appreciation and vasopressin release during the hyperglycemic study, although the sensitivity of the osmoreceptors remained unchanged. Analysis of the data in terms of plasma osmolality, corrected for the increase in blood glucose in the hyperglycemic study, revealed no differences in the osmotic thresholds for thirst or vasopressin release; sensitivity of the osmoreceptors also remained the same. Drinking abolished thirst and lowered plasma vasopressin concentrations before major changes in plasma sodium were observed. These results show that insulin dependent diabetic patients osmoregulate appropriately when moderately hyperglycemic but that the threshold plasma sodium for vasopressin secretion and thirst appreciation is lowered by an unknown mechanism. PMID- 2923251 TI - Effect of fasting on glucose turnover in a carnivorous fish (Hoplias sp). AB - Intravenous glucose tolerance tests and measurements with [6-3H]glucose of rate of glucose replacement, transit time, and body glucose mass were performed in fed and fasted Hoplias malabaricus. Both glycemia levels and the rate of decline of blood glucose following intravenous administration of 500 mg/kg glucose were significantly lower in 60-day-fasted than in fed fish. Changes in plasma free fatty acids were opposite to those in blood glucose. The rate of glucose replacement, calculated graphically from mean +/- 3 SE plots of glucose specific radioactivity, was 0.71 (0.66-0.77) mg.kg-1.min-1 in fed H. malabaricus and decreased to 0.51 (0.46-0.56) mg.kg-1.min-1 after 60 days without food, with a concomitant reduction of body glucose mass (mmin, 138 vs. 83 mg/kg). In fish starved for 10 mo the rate of glucose replacement and body glucose mass were further reduced to 0.35 (0.29-0.42) mg.kg-1.min-1 and 57 mg/kg (mmin), respectively. It is concluded that a progressive decline in the rate of glucose utilization contributes to the adaptation of fish to prolonged fasting. PMID- 2923252 TI - Administering triazolam on a circadian basis entrains the activity rhythm of hamsters. AB - A single injection of the short-acting benzodiazepine, triazolam, can induce permanent phase shifts in the circadian rhythm of locomotor activity in free running hamsters, with the direction and magnitude of the phase shifts being dependent on the circadian time of treatment. The shape of the "phase-response curve" to triazolam injections is totally different from that for light pulses. These findings raise the possibility that repeated injections of triazolam on a circadian basis might be capable of entraining the circadian pacemaker underlying the activity rhythm of hamsters and that the entrainment pattern might differ from that observed in animals entrained to light pulses. To test this hypothesis, blind hamsters received intraperitoneal injections of triazolam (or vehicle) every 23.34, 23.72, 24.00 or 24.66 h for 19-20 days, and the effect of these injections on the period of the rhythm of wheel-running behavior was determined during and after treatment. Repeated injections of 0.1 mg triazolam at these time intervals resulted in the entrainment of the activity rhythm in 36 of 40 animals, whereas 0 of 40 animals entrained to vehicle injections. Importantly, the phase relationship between triazolam injections and the circadian activity rhythm was dependent on the period of drug treatment and could be predicted from the phase response curve to single injections of triazolam. These phase relationships are dramatically different from those observed between the activity rhythm and 1-h light pulses presented at similar circadian intervals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2923253 TI - Evidence for a physiological role for CCK in the regulation of food intake in mice. AB - The effects of L-364,718, a cholecystokinin receptor antagonist, on cholecystokinin octapeptide-induced inhibition of food, and its effect on food intake when given alone, were studied in mice using several different feeding paradigms. In all studies, L-364,718 (100 micrograms/kg, 1.0 mg/kg) reversed the ability of cholecystokinin octapeptide to decrease food intake. L-364,718 enhanced food consumption compared with controls in nonfasted mice (100 microgram/kg) and in prefed mice (50, 100, 250 micrograms/kg). The number of reinforcements, using a lever press, was also enhanced by L-364,718 (100 micrograms/kg) compared with control. In other paradigms, L-364,718 failed to enhance food intake. These results are compatible with the suggestion that cholecystokinin may play a physiological role in the regulation of food intake. PMID- 2923254 TI - Failure of chronic beta-adrenergic blockade to inhibit overfeeding-induced thermogenesis in humans. AB - The effect of the beta-adrenergic antagonist propranolol on the increase in resting metabolic rate (RMR) induced by overfeeding was examined to determine whether increased beta-adrenergic activity contributes to this response. Six male subjects who were overfed with carbohydrate (1,600 excess kcal/day) for 10 days without drug treatment (control group) had increases (compared with values after 10 days of weight maintenance) in RMR after 6 days [0.24 +/- 0.06 kcal/min (22%)] and 10 days of overfeeding [0.17 +/- 0.03 kcal/min (15%)]. Eight male subjects were given a weight-maintenance diet for 10 days with oral propranolol treatment (40-60 mg every 6 h) over the last 7 days of this period. Five of these subjects were then overfed for 10 days, and three remained on the weight-maintenance diet; propranolol treatment continued until the end of the study. Propranolol significantly reduced RMR (mean 9%) before the onset of overfeeding but did not prevent increases in RMR after 6 days [0.18 +/- 0.05 kcal/min (16%)] and 10 days of overfeeding [0.17 +/- 0.03 kcal/min (15%)]. In the subjects who remained on the weight-maintenance diet throughout the study, there was no reversal of propranolol's initial reduction of RMR that would have falsely elevated the overfeeding effect. These data provide further evidence that the increase in RMR induced by overfeeding in humans is not mediated by increased beta-adrenergic activity. PMID- 2923255 TI - Determinants of arterial pressure after chronic spinal transection in rats. AB - The present study was conducted to determine whether sympathetic vasoconstrictor activity is a determinant of mean arterial pressure (MAP) hours and days after cervical spinal transection (CST) in unanesthetized rats. MAP on the 2 days before CST was 107.2 +/- 3.6 and 103.3 +/- 3.0 mmHg, respectively, and fell to 77.7 +/- 1.1 mmHg on day 1 after CST. MAP returned to control levels over the course of the study and, by day 9 after CST, was not statistically different from control (98.6 +/- 3.4 mmHg). Neither autonomic ganglionic blockade nor alpha adrenergic blockade affected MAP the 1st day after CST. Similarly, alpha adrenergic blockade was without effect on days 3, 5, and 7 after CST. Administration of a vasopressin V1-antagonist had no effect on MAP on day 1 or day 8 after CST. However, blockade of angiotensin-converting enzyme with captopril decreased arterial pressure both on day 1 (-22.1 +/- 2.6 mmHg) and day 8 (-23.3 +/- 2.9 mmHg) after CST. We conclude that neither sympathetic nor vasopressin vasoconstrictor activity affected MAP within the 1st wk after CST. Although the vasoconstrictor actions of angiotensin II were important, these effects were not responsible for the normalization of MAP observed after CST. PMID- 2923256 TI - Effects of chronic icv infusion of vasopressin on sleep-waking cycle of rats. AB - The effect of arginine vasopressin (AVP) on the duration and the relative proportion of sleeping and wakeful periods has been investigated. Vigilance states were determined by visual scoring of polygraphic recordings from unrestrained rats. Animals were implanted with a cannula into the third ventricle through which AVP or related drugs, dissolved in artificial cerebrospinal fluid, were infused at a constant rate by an osmotic pump. Polygraphic data were collected 24 h/day from day 4 to day 9. Recordings were continued for 3 additional days during AVP recovery. AVP infusions significantly increased the amount of time spent in waking compared with control or recovery periods (12%). This effect was mimicked by an AVP agonist (2-phenylalanine, 8-ornithine oxytocin). Oxytocin, a peptide structurally close to AVP, induced a mild change in waking time. The infusion of an AVP antagonist, 1-desaminopenicillamine-2-(O methyl)tyrosine-arginine vasopressin (dPTyr(Me)AVP), or of anti-AVP antibodies significantly decreased duration of waking. The infusion of antioxytocin antibodies did not modify the duration of waking. The effects of structural analogues of AVP relatively specific for each type of peripheral AVP receptor indicated the participation of a V1-like AVP receptor in the action of AVP on waking time. During infusion of anti-AVP antibodies and dPTyr(Me)AVP and during the first days of recovery from AVP infusion, the ultradian rhythmic distribution of sleep and wakefulness was still present, but the amplitude of the circadian rhythm was reduced. PMID- 2923257 TI - Comparison of intracerebroventricular and intracarotid infusions of PGE2 in conscious sheep. AB - Conscious sheep chronically prepared with nonocclusive indwelling vascular and cerebroventricular catheters were used to compare hemodynamic, hematologic, hormonal, and behavioral responses of intracarotid (ic) prostaglandin E2 (PGE2) to intracerebroventricular (ivt) PGE2. PGE2 had less potent hemodynamic effects when infused ivt than when infused ic. Intracarotid PGE2, 100 ng.kg-1.min-1, increased arterial pressure and heart rate 31 mmHg and 26 beats/min, respectively (P less than 0.01), whereas ivt PGE2, 300 ng.kg-1.min-1, did not alter heart rate and increased arterial pressure 9 mmHg (P less than 0.01). Both ic and ivt PGE2 increased packed cell volume 3% (P less than 0.01). Neither ic nor ivt PGE2 caused changes in plasma concentrations of epinephrine or norepinephrine. Despite ivt PGE2S less potent hemodynamic effects, ivt administration of PGE2 decreased plasma osmolality 2 mosmol/kg (P less than 0.05) and sodium concentration 2 meq/l (P less than 0.01) and increased plasma vasopressin concentration 2.5-fold (P less than 0.05). Intracerebroventricular PGE2 also caused some physical and behavioral changes that were not observed during ic PGE2 administration or during ivt infusion of vehicle. These changes included pupillary constriction, vocalization, and coughing. We conclude that PGE2 given ivt may not reach the same sites in the brain as does ic PGE2 or that ivt PGE2 may reach the same sites in different concentrations. PMID- 2923258 TI - Central effect of angiotensin II on baroreflex regulation in conscious rabbits. AB - Central effects of angiotensin II (ANG II) on arterial baroreflex control of renal sympathetic nerve activity (RSNA) and heart rate (HR) were examined in conscious rabbits. Intravenous infusions of ANG II (5-320 ng.kg-1.min-1) significantly reduced the baroreflex inhibition of HR compared with phenylephrine (PE) (0.5-16 micrograms.kg-1.min-1), whereas reflex inhibition of RSNA was unaltered. Background intravenous infusions of ANG II did not alter the baroreflex responses of RSNA nor HR to increases (with PE) or decreases in mean arterial pressure (with nitroglycerin or inferior vena cava occluder). When ANG II was infused into the vertebral artery (VA) the integrated pressor response was greater than intravenous infusions. Progressive VA infusions of ANG II resulted in a significantly blunted baroreflex inhibition of HR compared with intravenous infusions, whereas the reflex inhibition of RSNA was identical between VA and intravenous infusions. These results suggest that ANG II produces central pressor effects via a hindbrain site and reduces baroreflex inhibition of HR without altering baroreflex inhibition of RSNA. PMID- 2923259 TI - Prolactin stimulates food intake in the absence of ovarian progesterone. AB - Increases in serum estrogen inhibit food intake. Conversely, progesterone stimulates food intake, probably via its antiestrogenic action. We have reported that elevated serum prolactin also stimulates food intake in female rats. It is unclear whether this effect is mediated through elevated levels of progesterone. The present study investigated the effects of prolactin on food intake and brown fat activity in the absence of progesterone. Female Osborne-Mendel rats were assigned to one of six groups: sham operated (Sham, n = 10), ovariectomized (OVX, n = 10), OVX + low estrogen (EL, n = 11), OVX + EL + prolactin (PIT, n = 9), OVX + high estrogen (EH, n = 10), and OVX + EH + PIT (n = 8). Estrogen levels were elevated by Silastic implants. Prolactin levels were elevated through pituitary transplants placed under the kidney capsule. Nine days postsurgery, food intake was significantly higher in OVX vs. Sham rats. Estrogen-treated rats (OVX + EL and OVX + EH) had significantly suppressed food intake values compared with both Sham and OVX animals. Finally, hyperprolactinemic rats (OVX + EL + PIT and OVX + EH + PIT) ate significantly more food than did estrogen-treated rats without pituitary explants. Despite the hyperphagia, no significant differences in brown fat GDP binding were observed. These data indicate that prolactin stimulates food intake in the absence of ovarian progesterone. PMID- 2923260 TI - Regulated nocturnal hypothermia induced in pigeons by food deprivation. AB - The daily body temperature (Tb) cycle of pigeons is altered by food deprivation in that Tb falls to lower and lower levels on consecutive nights after the onset of deprivation, whereas the Tb levels during corresponding days remain nearly unchanged. Manipulations of spinal cord temperature, a major feedback parameter in the avian thermoregulatory system, reveal that episodes of nocturnal hypothermia are regulated. The spinal cord threshold temperature for inducing increases in metabolic heat production falls to progressively lower levels each night and returns to normal euthermic levels during the day. PMID- 2923261 TI - Central respiratory modulation of medullary sympathoexcitatory neurons in rat. AB - The central respiratory generator exerts a modulatory influence on sympathetic nerve discharge. In cats the sympathoexcitatory neurons of the rostroventrolateral medulla (RVL) exhibit central respiratory modulation as well. Because RVL sympathoexcitatory neurons are largely responsible for the maintenance of sympathetic vasomotor tone, it is likely that the modulation of these neurons accounts for the central respiratory modulation of sympathetic discharge. In the present study experiments were performed to characterize the pattern of respiratory modulation of lumbar sympathetic nerve discharge (LSND) in the halothane-anesthetized rat. Phrenic-triggered averaging of LSND exhibited a small depression coincident with the onset of the phrenic burst followed by a large peak that was coincident with the cessation of the phrenic burst. Phrenic triggered histograms of the activity of RVL sympathoexcitatory neurons exhibited three patterns of central respiratory modulation: inspiratory depression (I), inspiratory peak (II), and early inspiratory depression followed by a postinspiratory peak (III), a pattern that was very similar to that seen in LSND. Both nerve recording and single-unit recording experiments were performed in vagotomized rats with or without intact barosensory afferents. A comparison of the results suggested that, in the rat, the baroreflex does not modify or contribute to the central respiratory modulation of sympathetic output. Finally, a comparison was made between presumed nonadrenergic pacemaker-like neurons and putative C1 adrenergic neurons in the RVL. No differences were found in the patterns of central respiratory modulation. PMID- 2923262 TI - Effect of sympathetic blockade on diurnal variation of hemodynamic patterns. AB - Heart rate, stroke volume, and intra-arterial blood pressure were monitored continuously in each of four monkeys, 18 consecutive h/day for several weeks. The mean heart rate, stroke volume, cardiac output, systolic and diastolic blood pressure, and total peripheral resistance were calculated for each minute and reduced to hourly means. After base-line data were collected for approximately 20 days, observation was continued for equal periods of time under conditions of alpha-sympathetic blockade, beta-sympathetic blockade, and double sympathetic blockade. This was achieved by intra-arterial infusion of prazosin, atenolol, or a combination of both in concentration sufficient for at least 75% reduction of response to injection of agonists. The results confirmed previous findings of a diurnal pattern characterized by a fall in cardiac output and a rise in total peripheral resistance throughout the night. This pattern was not eliminated by selective blockade, of alpha- or beta-sympathetic receptors or by double sympathetic blockade; in fact, it was exacerbated by sympathetic blockade, indicating that the sympathetic nervous system attenuates these events. Because these findings indicate that blood volume redistribution is probably not the mechanism mediating the observed effects, we have hypothesized that a diurnal loss in plasma volume may mediate the fall in cardiac output and that the rise in total peripheral resistance reflects a homeostatic regulation of arterial pressure. PMID- 2923263 TI - Effects of brain natriuretic peptide on renal nerve activity in conscious rabbits. AB - Responses of renal nerve activity (RNA) to intravenous infusion of brain natriuretic peptide (BNP) were examined in chronically instrumented conscious rabbits with all baroreflexes intact, sinoaortic baroreceptor denervation (SAD), and SAD plus vagotomy. In intact rabbits, an infusion of BNP at a rate of 0.3 microgram.kg-1.min-1 for 30 min decreased mean arterial pressure (MAP) by 8 +/- 1 mmHg and increased RNA by 48 +/- 4% but did not alter heart rate (HR). The decrease in MAP in SAD rabbits (20 +/- 3 mmHg) was greater than in intact rabbits, whereas RNA increased less (21 +/- 7%). After SAD plus vagotomy, BNP lowered MAP by 25 +/- 4 mmHg, whereas RNA was not altered significantly. To further examine the effects of BNP on baroreflex control of HR and RNA, the baroreceptors were stimulated or unloaded by raising or lowering MAP by injections of phenylephrine or glyceryl trinitrate, respectively. The maximum change in each HR or RNA response to phenylephrine or glyceryl trinitrate was plotted against the maximum change in each MAP response and a logistic function curve was fitted to the MAP-HR and MAP-RNA relationship. BNP did not alter the slope of either curve but shifted both curves to the left. These results indicate that 1) in intact rabbits, BNP increases RNA due to sinoaortic and cardiopulmonary baroreflexes and 2) BNP resets the baroreflex control of HR and RNA to a lower arterial pressure. PMID- 2923264 TI - Evidence for a regenerative capacity in adult mammalian cardiac myocytes. AB - Cardiac muscle does not contain a copopulation of myogenic cells and is mitotically inactive; hence, any regenerative capacity of the myocardium most likely originates from viable fragments of damaged cells rather than mitogenic activity. To assess the extent of such tissue recovery, single doses of the drug bupivacaine were used to induce degeneration of rat ventricular myocytes, and histological evidence for tissue recovery was sought. Up to 1 wk posttreatment, extensive degeneration was found around the injection site. At 2 wk, evidence of regeneration could be seen, and at 3 wk posttreatment, some relatively normal looking tissue was found. PMID- 2923265 TI - The somatosensory evoked potentials of normal infants: influence of filter bandpass, arousal state and number of stimuli. AB - Median nerve somatosensory evoked potentials (SEPs) were investigated in 35 normal newborns aged 0-5 days. During stimulation at a regular frequency of 0.5/s, potentials deriving from cervical (CS2-Fz) or scalp (C3'-Fz) level were recorded with five different bandpasses (1-100 to 100-5,000 Hz (-6 dB/oct], with a variable number of stimuli (25-350) and in different arousal states: awake or in irregular sleep (non-quiet), or in regular sleep (quiet). The 1-100 Hz filter introduced a slight distorsion of the N13 and N19 (1) and (2) potentials but a better signal-to-noise ratio compared with the other filter settings. A 20-5,000 Hz bandpass resulted in an inacceptable distorsion of the N19 (1) and (2) peak. For the 100-5,000 Hz bandpass an almost complete suppression of the cortical components was obtained. With a 1-100 Hz bandpass a N13 and a N19 potential could be recorded in all infants; in 75% of them a bilobed N19 peak was present. In the quiet state (n = 13) either a bilobed N19 peak was observed with prolonged N19 (1) and (2) peak latencies compared with the non-quiet state or a large unilobed N19 wave. An increase in the number of stimuli from 25 to 100 resulted in a decrease of 33% in the amplitude of the N19(1) peak. We advocate to record SEPs in the neonatal period with a filter bandpass of 1-100 Hz and with a low number of stimuli (25-50), with attention for the arousal state of the infant. PMID- 2923266 TI - The influence of postmenstrual age estimation on the scatter of brainstem auditory evoked potential latencies. AB - In normal twins the brainstem auditory evoked potential (BAEP) was recorded. The inter-individual variation of the I-V peak latency-interval within the twins appears to be of the same order of magnitude as the variation of the I-V peak latencies generally observed in infants. Consequently we conclude that in low risk twins the inter-individual variation of the I-V peak latencies of the BAEP is maximally 0.4 msec and cannot be ascribed to a difference in postmenstrual age. PMID- 2923267 TI - Porencephaly and hydranencephaly: a neuropathological study of four autopsy cases. AB - Four autopsy cases of porencephaly and hydranencephaly were evaluated clinico pathologically. The patients showed profound mental retardation, convulsive seizures and spastic quadriplegia. The life spans were much shorter in the hydranencephalic cases. Pathologically, the cerebral cortex in the vicinity of the parenchymal defects often showed an abnormal cytoarchitecture, which appeared to be closely correlated with superficial glial proliferation. Several neurofibrillary tangles were found in the nucleus basalis of Meynert and the locus ceruleus in a 23-year-old porencephalic patient, and so-called grumose degeneration of the dentate nucleus in three patients, including a 2-month-old hydranencephalic boy. It is suggested that extensive cerebral defects may cause neuronal degeneration of the subcortical nuclei. PMID- 2923268 TI - Hypoglycemia in a child with congenital muscular dystrophy. AB - Since skeletal muscle is an important source of precursor for gluconeogenesis, it would not be surprising if carbohydrate metabolism was altered in some muscle disorders. We report a 7-10/12-year-old white male with congenital muscular dystrophy whose recurrent episodes of vomiting and dehydration were due to fasting hypoglycemia. He was found to have a blood glucose of 21 mg/dl with an episode of vomiting and dehydration. Diagnostic fasting replicated the symptoms and hypoglycemia. Associated laboratory findings included hypoalaninemia, ketonemia, and acidosis. With use of frequent feedings, there were no further episodes over 1-9/12 years of observation. To our knowledge this is the first report of hypoglycemia complicating muscular dystrophy. However, hypoglycemia may not be diagnosed because of the nonspecific nature of the symptoms. Hypoglycemia should be considered when children with reduced muscle mass develop otherwise unexplained vomiting. PMID- 2923269 TI - The effect of intraventricular interferon on subacute sclerosing panencephalitis. AB - Two patients with subacute sclerosing panencephalitis (SSPE) were treated with intraventricular alpha interferon (IFN-alpha) via an Ommaya reservoir for 20-57 months. The clinical course of the disease was followed for 20-67 months. Clinical improvement was observed after daily intraventricular administration of IFN in one case. There were no serious complications or side effects during interferon therapy except for the fever. Intraventricular administration of IFN appears superior to intrathecal administration for long-term treatment in several respects and is considered to be a potential therapeutic modality for SSPE. PMID- 2923270 TI - Changing views of NMR: automated high-resolution NMR with a sample changer. PMID- 2923271 TI - Chemical ionization of laser-desorbed neutrals in a Fourier transform mass spectrometer. PMID- 2923272 TI - Modification of a high-efficiency passive sampler to determine nitrogen dioxide or formaldehyde in air. PMID- 2923273 TI - Analytical applications of polarimetry, optical rotatory dispersion, and circular dichroism. PMID- 2923274 TI - Separation of serotonin from catechols by capillary zone electrophoresis with electrochemical detection. AB - Capillary zone electrophoresis with electrochemical detection is demonstrated with columns having only 9-microns inner diameter. Amperometric detection limits of 0.7 amol are reported for serotonin. The difficult problem of resolving serotonin and dopamine--two neurotransmitters of interest having similar electrophoretic mobilities--is addressed by chemical means to improve selectivity. These include buffer modification with 2-propanol and a system employing borate complexation of the catechol in combination with sodium dodecyl sulfate micelles. PMID- 2923275 TI - Diameters and cross-sectional areas of branches in the human pulmonary arterial tree. AB - Measurements were made of the diameters of the three branches meeting at each of 1,937 bifurcations in the pulmonary arterial tree, using resin casts from two fully inflated human lungs. Cross-sectional areas of the parent branch and of the daughter branches were calculated and plotted on a log-log plot, which showed that mean cross-sectional area increases in a constant proportion of 1.0879 at bifurcations. The mean value of the ratio of daughter branch diameters at bifurcations was 0.7849. The mean value of the exponent z in the equation flow = k (diameter(z)) was found to be 2.3 +/- 0.1, which is equal to the optimal value for minimizing power and metabolic costs for fully developed turbulent flow. Although Reynolds number may exceed 2,000 in the larger branches of the pulmonary artery, turbulent flow probably does not occur, and in the peripheral branches Reynolds number is always low, excluding turbulent flow in these branches. This finding seems to be incompatible with the observed value of z. A possible explanation may be that other factors may need to be taken into account when calculating the theoretical optimum value of z for minimum power dissipation, such as the relatively short branches and the disturbances of flow occurring at bifurcations. Alternatively, higher arterial diameters reduce acceleration of the blood during systole, reduce turbulent flow, and increase the reservoir function of the larger arteries. These higher diameters result in a lower value of z. PMID- 2923276 TI - Progesterone secretion and mitochondrial size of aging porcine corpora lutea. AB - A functional dependency between the nongravid uterus and the ovaries is essential to luteolysis and the return to estrus in the pig. After mating of gilts, the corpora lutea develop, and they are required for the maintenance of pregnancy to a normal duration of about 114 days. Hysterectomy of luteal phase (day 6) nongravid gilts results in persistence of the corpora lutea to 150 days. We report that these corpora secrete greater quantities (P less than 0.025) of progesterone than during the later half of gestation (days 54-108). Although aging corpora lutea remain functional for at least an additional 35 days, an abrupt reduction by half in progesterone secretion (16 ng/ml) occurs about day 114 in hysterectomized gilts that coincides with the prepartum decrease to basal serum levels (less than 0.5 ng/ml) at parturition (day 114) and during lactation. Aging corpora lutea remain large (averaging greater than 450 mg) on days 124 and 136 in hysterectomized gilts, whereas they regress (averaging less than 75 mg) in the lactating dams. Mitochondria continue to increase in size in aging corpora lutea of hysterectomized gilts until day 136; in contrast, they decrease during the postpartum period in lactating dams. A precisely timed signal, possibly of ovarian origin or from the CNS and pituitary gland, entrains in hysterectomized and pregnant pigs at day 113 that results in marked shifts in relaxin and progesterone secretion. Progesterone secretion and mitochondrial features suggest that porcine corpora lutea seem genetically controlled and are preprogrammed at estrus for the duration of pregnancy, regardless of the presence of conceptuses or absence of the uterus. PMID- 2923277 TI - Progesterone promotes a massive infiltration of the rat uterine cervix by the eosinophilic polymorphonuclear leukocytes. AB - Rat uterine cervices contained an eosinophilic infiltrate during labor, whereas samples of cervices obtained from nonpregnant controls had no infiltrate. A heavy eosinophilic invasion, which closely resembled that of the cervix uteri at term, could be reproduced in ovariectomized rats following progesterone administration, but not in spayed rats injected with estrogen. Light and electron microscopic evidence showing a widespread collagenolysis in the cervical stroma at term is presented. This collagenolysis follows the eosinophilic invasion. On the basis of these observations, a possible role for the eosinophilic infiltrate of the uterine cervix is discussed. PMID- 2923278 TI - Development of spermatozoa in the rhea. AB - We have examined the ultrastructural changes that take place during spermiogenesis in the rhea. Spermatozoa are characterized by a curved head and a midpiece. A thin rod extends from the anterior tip of the spermatozoon through the center of the nucleus. A 3-mu-long distal centriole occupies the entire midpiece. The principal piece is characterized by a small fibrous sheath and tiny dense fibers that are only observed in the region of the principal piece, which is immediately behind the annulus. During development a circular manchette surrounds the nucleus of young spermatids. Later the microtubules of the circular manchette become reorganized into a longitudinal manchette. A long distal and short proximal centriole are observed in early round spermatids. The distal centriole becomes associated with the plasma membrane. Later the proximal centriole is observed in association with the nucleus. The area around the centriole pair then accumulates dense material, which is associated with either the centrioles or the circular manchette. The longitudinal manchette forms and then disappears and mitochondria subsequently associate with the distal centriole. The long centriole of the rhea enables this species to develop a midpiece similar to the midpiece of mammalian sperm without the complex intercellular movements that characterize mammalian spermiogenesis. PMID- 2923279 TI - Immunocytochemical localization of hepatic fatty acid binding protein in the rat intestine: effect of fasting. AB - Localization of hepatic fatty acid binding protein (h-FABP) in the small and large intestines of rats was studied by light and electron microscopic histochemistry using the peroxidase-antiperoxidase (PAP) method. In the small intestine of rats fed ad libitum, an intense FABP immunoreactivity was confined to the absorptive epithelial cells of the villi, but not of the crypts. The lowest margin of the immunoreactive cell sheet was closer to the crypts in the proximal than in the distal portions of the small intestine. In the large intestine, FABP immunoreactivity was present in the surface epithelial cells, with higher intensity in the proximal than in the distal portions of the intestine. After fasting rats for two days, many crypt cells exhibited intense immunoreactivity for h-FABP, resulting in an extension of the lowest margin of the immunoreactive cell sheet deep into the crypts. Such expansion of the immunoreactive cell population was reversed by refeeding the animals. With regard to the intracellular localization of immunoreactivity in the jejunum, the basolateral portion of the cytoplasm exhibited a more intense immunoreaction than the apical portion in the majority of immunoreactive cells lining the villi, whether the animals were fed or fasted. The immunoreactive products appeared in the cytoplasmic matrix without association with any subcellular structures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2923280 TI - Neural crest ablation does not alter pulmonary vein development in the chick embryo. AB - Cranial neural crest, which extends from the mid-diencephalon to somite five, plays an integral role in development of pharyngeal arch derivatives and supplies mesenchyme to the aortic arch arteries. Neural crest cells in pharyngeal arches three, four, and six migrate to the heart and are involved in aorticopulmonary and conotruncal septation. Ablation of the "cardiac" neural crest cells in chick embryos results in a variety of outflow tract anomalies, including persistent truncus arteriosus. Although other studies have shown the importance of the neural crest in the development of the cardiac outflow tract, the role of neural crest in venous development has not been established. This investigation evaluates the effect of cardiac neural crest ablation on the morphological development of the pulmonary vein. The presence of the pulmonary vein was confirmed initially at early stage 15 using histological sections and computer reconstructions of serially sectioned, normal embryos. India ink injections demonstrated a complete, patent pulmonary circuit at stage 18. Cardiac neural crest was ablated at stages 8-10. Operated, sham-operated, and control embryos were sacrificed at incubation day 11, and acrylic plastic casts prepared of the intravascular compartment. In experimental embryos with persistent truncus arteriosus, there were no morphological differences in the pulmonary veins, compared with shams and controls. These data indicate that the lesions of the cardiac neural crest have little morphological impact on pulmonary vein development. It is concluded that alterations in the cardiac neural crest are not involved in venous anomalies such as cor triatriatum and total or partial anomalous pulmonary venous return. PMID- 2923281 TI - Morphogenesis of the secondary palate in mouse embryos with special reference to the development of rugae. AB - Morphological studies of secondary palate formation, with special reference to the development of rugae, were carried out on Jcl:ICR mouse embryos. Three rugae were observed on the anterior part of the future oral surface of the vertically developing palatal shelves in 13-day embryos. Rugae increased in number as the development of the palatal shelves proceeded, and five to six prominent rugae were observed in 14-day embryos just prior to shelf elevation. The folding of these five to six rugae progressed in conjunction with the formation of a sharp, valley-like groove at the base of the anterior two-fifths of the vertical palatal shelves. As palatal shelves elevated, the groove disappeared gradually, and, accordingly, the folding of rugae loosened. In the groove region, the superficial epithelial cells were roundish, while the basal ones were elongated. Such characteristic features were no longer observed when the disappearance of the groove was completed. Eight rugae were observed on the future hard palate of 14 day embryos with already completed palatal fusion. An additional ruga was frequently found in 15-day embryos, and the pattern then was almost the same as that of an adult. Epithelial thickening and condensation at the rugae region, as well as mesenchymal condensation under the epithelium of the rugae, were confirmed in embryos both before and after elevation of the palatal shelves. There is a possibility that these structural characteristics observed in the epithelial and mesenchymal cells of the rugae and groove regions may be related to palatal shelf elevation. PMID- 2923282 TI - Differential expression of galactose and N-acetylgalactosamine residues during fetal development and postnatal maturation of rat glomeruli as revealed with lectin conjugates. AB - A battery of fluorochrome- or peroxidase-coupled lectins, reacting with alpha- or beta-galactose (Gal), terminal N-acetylgalactosamine (GalNAc), or Gal-(beta 1-3) GalNAc residues, was used to study the emergence and distribution of cellular glycoconjugates in developing and adult rat glomeruli. Neuraminidase pretreatment of the specimens was applied to monitor the maturation of the glomerular sialoglycoprotein coat. In the adult glomeruli, the lectin conjugates applied reacted sparsely or not at all, but most of them showed an increased reactivity with podocytes and/or the glomerular basement membrane after neuraminidase treatment. In the embryonic glomeruli, lectins reacting with beta-Gal residues prominently bound to the basement membranes, as revealed in double-staining with laminin antibodies. This reactivity decreased first during late postnatal development. Some terminal Gal-(beta 1-3)-GalNAc residues were noted in the earliest podocytes, but obviously soon became covered by sialylation. Furthermore, the developing podocytes prominently displayed alpha-Gal residues, as marked by Maclura pomifera (MPA) and Jacalin reactivities but not by the GSA-I conjugates. During postnatal maturation these reactivities also decreased. The GalNAc-specific Helix pomatia (HPA) and Helix aspersa (HAA) agglutinins bound to basement membranes of evolving podocytes but later revealed in the podocytes only a Golgi-like cytoplasmic reactivity. These two lectins showed a marked difference in their binding to tubular basement membranes. In lectin blotting experiments of electrophoretically separated polypeptides transferred onto nitrocellulose, the peanut agglutinin (PNA) and MPA conjugates revealed upon neuraminidase treatment a broad Mr 140,000 polypeptide, compatible with podocalyxin, both in isolated developing and adult glomeruli. The MPA conjugate revealed a similar polypeptide in developing glomeruli, even without neuraminidase treatment. Similar experiments with the HPA and HAA conjugates revealed different polypeptides in both adult and developing glomeruli. Obviously, in the rat kidney the maturation of the podocyte sialoglycoprotein coat and the glomerular basement membranes are multiphasic processes that continue even during late postnatal development. PMID- 2923283 TI - Body weight gain as related to craniofacial and calvarial volumetric changes in growing rabbits. AB - This investigation was conducted to evaluate the relationship between calvarial and craniofacial volumetric growth relative to body weight gain. Ten male New Zealand white rabbits received spherical tantalum bone markers in the nasal, frontal, parietal, and temporal bones: a minimum of two in each bone segment. The animals were followed from age 32 to 144 days using a roentgen stereophotogrammetric system and an accurate scale. Implant stability was checked at each stereometric examination. Sutural growth and volumetric changes were computed and correlated to weight increase. Successive calvarial and craniofacial polyhedron expansion, as well as weight, showed considerable variability and interindividual variation throughout the observation period. Calculated coefficients of determination, linear regressions, and the correlation coefficients for each age interval demonstrated weak correlations, especially for calvarial to weight data. Consequently, this study suggests a low dependence of calvarial volumetric growth, reflecting the neural mass expansion on body weight development. Thereby, further indications of the low reliability of weight as a parameter of general health evaluation was provided. PMID- 2923284 TI - Effects of aging on the neurons within area 17 of rhesus monkey cerebral cortex. AB - A light and electron microscopic examination of area 17 of the visual cortex in well-fixed young (5-6 years) and old (25-35 years) rhesus monkeys was carried out to determine the effects of age on neurons. The analyses were made in a portion of area 17 on the lateral surface of the hemisphere just caudal to the lunate sulcus. Light microscopic measurements of the mean cortical depth in vertically oriented 1-micron-thick sections reveal no obvious thinning with age, and the mean diameters of neuronal nuclei do not change with age. On the basis of counts of neuronal profiles containing nuclei in 250-microns-wide strips of 1-micron thick sections passing through the entire depth of the cortex, no significant neuronal loss could be detected. These findings are consistent with our electron microscopic observations on this area of the cortex, for in the old monkeys the neurons show little cytological evidence of advanced age beyond the presence of a few lipofuscin granules, although the neuropil contains some profiles of degenerating small-caliber dendrites, myelinated axons, and a few axon terminals. Large vacuoles, some 10 microns or more in diameter, are present in the neuropil of the old animals. Some of these vacuoles appear to represent a late stage in the degeneration of myelinated axons, for they are bounded by a thin, laminated sheath. Other large vacuoles, of unknown origin, often contain membranous debris and have an attenuated limiting membrane. It is concluded that the cell bodies of neurons in area 17 of old rhesus monkeys do not show significant structural changes due to age, although some of the neuronal processes in the neuropil are affected. PMID- 2923285 TI - Foveal regions of bird retinas correlate with the aster of the inner nuclear layer. AB - A radiate specialization, the aster, has been found in whole-mount retinas of birds and is associated to each one of the temporal and nasal fovea, with the one related to the convexiclivate nasal fovea more evident. This radial arrangement extends uniformly in all directions from the foveal pit. Transverse sections of the retina show that this structure is formed by bands of cells and bundles of fibers from the inner nuclear layer. PMID- 2923286 TI - Delayed muscle fiber transformation after foreign-reinnervation of excessive muscle tissue. AB - Following partial denervation motor units can increase (by self-reinnervation) as much as four to five times their normal size. To investigate the still unknown quantitative reinnervation capacity of a motor nerve in the case of foreign reinnervation, in adult male rats the denervated sternomastoid muscle was either self-reinnervated by its original nerve or foreign-reinnervation by the omohyoid nerve, which had to reinnervate the three times the amount of muscle fibers and six times the amount of muscle mass. After survival times of 7, 8, 9, or 10 months, nerves and muscles were investigated histochemically and immunohistochemically. The omohyoid nerve could fully reinnervate the sternomastoid muscle, but at 7 and 8 months this muscle still revealed nearly the same proportions of IIA and IIB fibers as were seen in the self-reinnervated sternomastoid at all stages. However, in the following 2 months a shift of the fiber pattern toward that of the normal omohyoid was observed, as evidenced by a strong increase in type IIB fibers (from 24% to 62%), at the expense of type IIA fibers. These findings are in contrast to those after foreign (cross) reinnervation of leg muscles where the fiber transformation (according to the foreign motor input) occurs in parallel with the reinnervation process during the first 2-3 months. The delayed fiber transformation observed could be the consequence of the highly enlarged peripheral field of the omohyoid motoneuron pool or could merely reflect a general difference between limb and neck muscles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2923287 TI - How should residual neuromuscular blockade be detected? PMID- 2923288 TI - Recovery of airway protection compared with ventilation in humans after paralysis with curare. AB - d-Tubocurarine (dTc) was administered intravenously to six healthy unanesthetized volunteers to assess the sensitivity to neuromuscular blockade of those muscles involved in protecting the airway against obstruction and/or aspiration relative to the muscles of inspiration. Each subject was given an intravenous bolus of dTc followed by an infusion to allow three different levels of inspiratory muscle weakness as measured by maximum inspiratory pressure (MIP). Levels of MIP were control (-90 cm H2O), -60, -40, and -20 cm H2O. Vital capacity (VC), hand grip strength (HGS), and end-tidal CO2 (PETCO2) were obtained at each level. At each level of weakness and at intermediate values during recovery, muscles of airway protection were functionally assessed by noting the MIP at which the maneuver could be accomplished and the MIP at which they could not. The mean of these two values was calculated for each subject. The tests were: 1) ability to swallow, 2) ability to perform a valsalva maneuver, 3) prevent obstruction of the airway, and 4) ability to approximate teeth. These were compared with head lift and straight leg raising. At maximum neuromuscular blockade (MIP of -20 cm H2O), VC was 2.0 liters, HGs was 0, and PETCO2 was normal. Muscles of airway protection were still incapacitated. Swallowing returned above MIP of -43 cm H2O, approximation of teeth above -42 cm H2O, airway obstruction above -39 cm H2O, and valsalva above 33 cm H2O. Thus, although ventilation may be adequate at MIP = -25 mmHg, the muscles of airway protection are still nonfunctional.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2923289 TI - Safety of supplementing axillary brachial plexus blocks. AB - The incidence of failed local anesthetic axillary blockade varies but can be as high as 20-30%. The authors propose to evaluate the safety of supplementing an axillary block with mepivacaine 30 min after the initial injection. An axillary blockade was performed on 10 healthy patients scheduled for forearm or hand surgery using a new catheter technique. Mepivacaine 1% with epinephrine (7 mg/kg) was administered initially and followed 30 min later by half the original dose (3.5 mg/kg). Plasma levels of mepivacaine were estimated at frequent intervals for 5 h after the initial injection. There were no symptoms or signs of local anesthetic toxicity, and plasma levels of mepivacaine remained below those that usually caused symptoms. In conclusion, the authors conclude that mepivacaine 1% with epinephrine (10.5 mg/kg) can be safely administered in divided doses into the axillary sheath within a 31-min period. PMID- 2923290 TI - Caudal epidural morphine for control of pain following open heart surgery in children. AB - The safety and efficacy of epidural morphine injected into the caudal space for control of postoperative pain following open cardiac surgery in children was studied. Thirty-two children between the ages of 2-12 yr for whom early postoperative tracheal extubation was anticipated were randomly assigned to control and study groups. Study subjects received a caudal injection of preservative free morphine sulfate (0.075 mg/kg) in preservative-free normal saline (5-10 ml) following completion of surgery, but prior to awakening and extubation of the trachea. Supplemental intravenous morphine administration and pain scores were recorded for 24 h. Patients in the study group received significantly less (P less than 0.03) morphine (0.32 mg.kg-1.24 h-1) and had significantly lower pain scores than did patients in the control group (0.71 mg.kg-1.24 h-1). The mean duration of complete analgesia in patients receiving caudally administered morphine was 6 h (range 2-12), but decreased analgesic requirements were noted for the entire 24 h. No respiratory depression was evident by clinical variables or repeated arterial blood gas values. Nausea without vomiting occurred in 4/16 patients in the study group. No patient described pruritus. The authors were unable to evaluate the occurrence of urinary retention because all patients had indwelling urinary catheters. They found caudal epidural morphine to be safe and effective in the treatment of postoperative pain in children following open heart surgery. PMID- 2923291 TI - Regional blood flow and tissue oxygen pressures of the collateral-dependent myocardium during isoflurane anesthesia in dogs. AB - The authors investigated the effects of isoflurane on blood flow and tissue oxygen pressures of a collateral-dependent myocardium. Seventeen dogs divided into two groups were studied 3-4 weeks after implantation of ameroid coronary artery constrictors to completely occlude the proximal part of the left anterior descending artery. Experiments were performed during anesthesia with an opiate that was infused intravenously throughout the experiments. In Group 1 (n = 9), measurements were obtained during control and during isoflurane- (1.6-2.2 vol%) induced hypotension (mean arterial pressure, 60 mmHg). In Group 2 (n = 8), the identical protocol was applied, but norepinephrine was infused to maintain normotension. Dipyridamole effects were studied in five animals of Group 2 after a second control period at least 1 h after discontinuation of isoflurane. Isoflurane-induced hypotension caused reductions of blood flow and surface tissue oxygen pressures in the collateral flow-dependent area. Vasodilation in the normal left ventricular areas was demonstrated by an unchanged blood flow despite a reduced oxygen consumption and by a significantly increased coronary sinus hemoglobin oxygen saturation. When arterial pressure was maintained at its control level by norepinephrine, tissue oxygen pressures remained constant and collateral as well as normal area flow increased significantly during isoflurane. Coronary vascular resistance was lower during administration of isoflurane and norepinephrine compared with that during isoflurane induced hypotension, suggesting a significant contribution of tissue oxygen demand in regulation of coronary vascular resistance. At comparable levels of arterial pressure and left ventricular oxygen consumption, normal zone blood flow was significantly higher during dipyridamole than during isoflurane and norepinephrine. Thus, isoflurane induced hypotension decreased blood flow and tissue oxygen pressures of collateral flow-dependent myocardial areas. However, neither isoflurane nor dipyridamole caused such alterations when arterial pressure was normal. PMID- 2923292 TI - Pulmonary resistance during halothane anesthesia is not determined only by airway caliber. AB - Studies of the effect of halothane on airway smooth muscle have used pulmonary resistance as an index of airway caliber. However, pulmonary resistance (RL) is the sum of airway resistance (Raw), which changes with airway caliber, and of tissue resistance (Rti), which depends on the pressure-volume hysteresis of the lung. To separate the effects of halothane on airway caliber from its possible effects on tissue pressure-volume hysteresis in the unstimulated lung and during bronchoconstriction, the authors measured both components of RL before and during vagus nerve stimulation in 12 dogs before and during halothane administration. Rti was always the major component of RL, constituting 77 +/- 14% (mean +/- SD) of RL before vagus nerve stimulation and 64 +/- 21% of RL during stimulation in the absence of halothane. Vagus nerve stimulation caused approximately equal increases in both Rti and Raw. Halothane attenuated the response of both Rti and Raw to vagus nerve stimulation in a dose-dependent fashion. At 1 MAC, the Rti response was 44 +/- 13% of its value before halothane administration and the Raw response was 32 +/- 12% of its value before halothane administration; these responses were not significantly different. The authors conclude that changes in RL during halothane administration are caused not only by changes in airway caliber, as previously assumed, but also reflect a significant effect of halothane on lung tissue pressure-volume hysteresis. PMID- 2923293 TI - Interaction of fentanyl and pentobarbital on peripheral and cerebral hemodynamics in newborn lambs. AB - The effects of 3.0 mg.kg-1 fentanyl on cerebral and peripheral hemodynamics alone and when combined with subanesthetic doses of pentobarbital (4.0 mg.kg-1), were studied in 11 unanesthetized, newborn lambs, in whom catheters had been previously inserted. After a control period, drugs were administered at 20-min intervals by intravenous bolus injection. Group 1 animals (n = 5) received fentanyl, pentobarbital, and naloxone (0.01 mg.kg-1), whereas Group 2 animals (n = 6) had the order of fentanyl and pentobarbital reversed. All animals responded to pain (withdrawal to tail clamping) and appeared conscious (eyes open, alert to sound) when either fentanyl or barbiturate was given alone. The combination of drugs, however, produced complete unresponsiveness. All of these effects were reversed by naloxone. Cardiac output did not change after either fentanyl or pentobarbital was administered individually but decreased significantly (29% in Group 1, 21% in Group 2) after administration of the combination of both. Mean arterial pressure and heart rate were unchanged. Cerebral blood flow, oxygen (O2) transport, and O2 consumption did not change after either administration of fentanyl or pentobarbital alone but decreased significantly after both (22%, 30%, 19%, respectively, in Group 1 and 35%, 40%, 38%, respectively, in Group 2). The decrease in cerebral O2 transport nearly paralleled the decrease in cerebral O2 consumption such that the ratio, the fractional O2 extraction, increased slightly. Fentanyl decreased kidney blood flow alone (24%) and in combination with pentobarbital (25%), although pentobarbital did so only when combined with fentanyl.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2923294 TI - Measurement of stroke volume with three-dimensional transesophageal ultrasonic scanning: comparison with thermodilution measurement. AB - The accuracy of measuring cardiac stroke volume with a new transesophageal phased array ultrasonic probe was investigated in 10 dogs. The method involved scanning the heart to obtain serial images covering the entire left ventricular cavity at end-expiration. An off-line computer analysis of the images was used to form three-dimensional reconstructions of the left ventricular cavity at end-diastole and end-systole, from which stroke volume was determined. Comparison with stroke volume determined by thermodilution during a wide range of hemodynamic conditions gave the following results for least-squares regression on 57 determinations (with the 95% confidence limits in parentheses): slope 0.95 (0.842-1.06), ordinate intercept 2.1 (2.0-2.2) ml, standard error of the estimate 4.1 ml, and correlation coefficient of 0.92 (0.87-0.95). Histologic examination of sections of esophagus surrounding the tip of the probe in nine dogs demonstrated minimal trauma to the esophageal wall, with eight specimens described as normal and one showing mild inflammation. The authors conclude that three-dimensional reconstruction of the left ventricular cavity from multiple transesophageal images offers a safe and accurate, although presently tedious, method for determining stroke volume. PMID- 2923295 TI - Mechanical factors do not influence blood flow distribution in atelectasis. AB - The contribution of mechanical factors to the vascular resistance of the atelectatic lung has been studied in vivo in the anesthetized open-chest dog. When the left lung was ventilated with an hypoxic gas mixture (while the right lung was ventilated with 100% O2), left lung blood flow decreased from 0.99 +/- 0.11 1.min-1 to 0.40 +/- 0.08 1.min-1 due to hypoxic pulmonary vasoconstriction (hypoxic stimulus PSO2 = 36.1 +/- 0.8 mmHg). When the left lung was made atelectatic, blood flow decreased to 0.65 +/- 0.11 1.min-1, consistent with a weaker hypoxic stimulus (PSO2 = 54.0 +/- 3.2 mmHg). With the addition of sodium nitroprusside infused intravenously, left lung blood flow increased to 1.05 +/- 0.14 1.min-1 during atelectasis, and to 0.61 +/- 0.09 1.min-1 during hypoxic ventilation, while flow remained at 0.94 +/- 0.18 1.min-1 during hyperoxic ventilation. When the results were plotted on pressure-flow diagrams, the hyperoxic, hypoxic, and atelectatic lung points fell on the same pressure-flow line in the presence of nitroprusside. It is concluded that hypoxic pulmonary vasoconstriction is the major (but not necessarily only) determinant of increased vascular resistance in the atelectatic lung, and that passive mechanical factors do not measurably affect blood flow distribution during open-chest atelectasis. PMID- 2923296 TI - Disruption of the rhythmic activity of the medullary inspiratory neurons and phrenic nerve by fentanyl and reversal with nalbuphine. AB - The effects of intravenous administration of fentanyl (50 and 100 micrograms/kg) on the discharge activity of the medullary inspiratory neurons and of the phrenic nerve were studied following vagotomy in nine decerebrate, paralyzed mechanically ventilated cats. In six cats, the inspiratory neurons explored were in the dorsal respiratory group (DRG) associated with the nucleus of the tractus solitarius (NTS), while in the remaining three, they were in the ventral respiratory group (VRG). In the former group, the rhythmic discharge of the inspiratory neurons was disrupted by fentanyl and replaced by a continuous discharge superimposed with irregularly occurring bursts. These changes were also reflected by the phrenic nerve discharge. Inspiratory neuronal activity increased significantly (P less than 0.05) at 1 and 5 min after completion of fentanyl injection. Disruption of the rhythmic activity of the inspiratory neurons and its replacement by a continuous and irregular discharge may lead to sustained contraction of inspiratory muscles and cessation of respiration. In the VRG, the activity of the inspiratory neurons was totally abolished by fentanyl. Thus, it appears that different groups of medullary inspiratory neurons have differential sensitivity to fentanyl. Nalbuphine, an opiate agonist-antagonist, restored the normal pattern and magnitude of the activity of the inspiratory neurons. PMID- 2923297 TI - The effect of halothane, enflurane, and isoflurane on the dynamic stiffness of rabbit papillary muscle. AB - The authors examined the effect of halothane, enflurane, and isoflurane on the dynamic stiffness of rabbit papillary muscles in Ba2+ contracture. Ca2+ was replaced by Ba2+ in order to constantly activate myofibrils. The dynamic stiffness of the contractured muscle was examined by exposing the muscle to sinusoidal length perturbations at frequencies of 0.05-30 Hz under two concentrations of anesthetic, approximately 0.5, and 1.5-2 mM, and at two Ba2+ concentrations, 0.5 and 1.5-2 mM. The anesthetics had no effect on the frequency (fmin) at which minimum stiffness occurred, but markedly decreased the stiffness modulus at high frequencies (Khi). The decrease in Khi was significant for all anesthetics at the P less than 0.05 level. Increasing the Ba2+ concentration from 0.5 to 1.5-2 mM in the presence of 0.5 mM of anesthetic resulted in a return of Khi to control levels. The authors conclude that halothane, enflurane, and isoflurane did not alter actin-myosin ATPase kinetics, because fmin was unchanged, but decreased the number of crossbridge interactions, because Khi was significantly decreased by all three anesthetics. PMID- 2923299 TI - The longitudinal distribution of pulmonary vascular resistance during unilateral hypoxia. AB - Pulmonary capillary hydrostatic pressure and the longitudinal distribution of pulmonary vascular resistance (arterial and venous components) can be determined by analysis of pressure decay curves following pulmonary artery occlusion. To validate this technique in intact animals, pulmonary artery occlusion pressure decay curves were obtained from both lungs in six anesthetized sheep during control conditions (100% O2) and during unilateral hypoxic ventilation (100% O2 versus 100% N2). Analysis of pulmonary artery occlusion pressure curves indicated the following: 1) in the hypoxic lung, unilateral hypoxia increased the precapillary portion of pulmonary vascular resistance from 72% of the total resistance to 89% of the total resistance in that lung; 2) in the nonhypoxic lung, unilateral hypoxia did not significantly affect the distribution of pulmonary vascular resistance; and 3) unilateral hypoxia produced no significant change in pulmonary capillary pressure in the hypoxic lung compared with control; however, pulmonary capillary pressure was significantly greater in the nonhypoxic lung. These results are consistent with other evidence that hypoxic pulmonary vasoconstriction acts locally and primarily affects resistance at the arteriolar level. Pulmonary artery occlusion pressure decay curve analysis appears to be a valid technique for the measurement of pulmonary capillary pressure and the longitudinal distribution of pulmonary vascular resistance in intact anesthetized animals. These measurements pertain only to the vasculature distal to the site of pulmonary artery occlusion with the catheter, and, thus, caution must be used when applying this technique in a setting of nonhomogenous lung injury. PMID- 2923298 TI - Halothane induces depressor responses to noxious stimuli in the rat. AB - The effect of halothane on hemodynamic responses to noxious stimuli was investigated in anesthetized male Sprague-Dawley rats. It was found that increasing the end-tidal halothane concentration from sub-MAC to supra-MAC levels was frequently associated with a reversal of the mean arterial pressure response to a noxious stimulus from a pressor response to depressor response. The depressor responses could be produced by noxious stimuli at several sites but were of greatest frequency (100%) and magnitude (up to -80 mmHg) after clamp application at the base of the tail. The depressor responses were often, but not always, accompanied by decreases in heart rate. The correlation coefficient between the changes in heart rate and the changes in mean arterial pressure caused by noxious stimuli was +0.61 (n = 9). The authors further characterized the depressor responses in an additional 18 rats. The depressor responses were not influenced by vagotomy or muscarinic cholinergic blockade and were associated with concurrent decreases in both cardiac output and systemic vascular resistance. The hemodynamic changes associated with the depressor responses were consistent with a centrally mediated withdrawal of sympathetic tone. Knowledge of this effect of halothane on the arterial blood pressure and heart rate responses to noxious stimuli may be important for correctly interpreting animal responses to noxious stimuli in the presence of general anesthetic agents, particularly because animals are frequently used to characterize both the potency and the hemodynamic effects of anesthetic agents. The presence of depressor responses also indicates that mean arterial pressure responses to noxious stimuli cannot be used as a linear index of anesthetic depth in rats anesthetized with halothane. PMID- 2923301 TI - Anesthetic management for oophorectomy in a patient with lymphangiomyomatosis. PMID- 2923300 TI - Whistling face syndrome: general anesthesia and early postoperative caudal analgesia. PMID- 2923302 TI - Airway management for unilateral lung lavage in children. PMID- 2923303 TI - Succinylcholine-induced hyperkalemia in a patient with metastatic rhabdomyosarcoma. PMID- 2923304 TI - All that quakes does not necessarily shiver. PMID- 2923305 TI - The use of a vinyl glove does not affect pulse oximeter monitoring. PMID- 2923306 TI - EKG artifacts during intraoperative evoked potential monitoring. PMID- 2923307 TI - High spinal anesthesia in an infant. PMID- 2923308 TI - Adverse reactions to non-ionic iodinated contrast media do occur during general anesthesia. PMID- 2923309 TI - More on anesthesia machines and malignant hyperpyrexia. PMID- 2923310 TI - A potential complication of fiberoptic intubation. PMID- 2923311 TI - Draft guideline for selection and use of disinfectants. PMID- 2923312 TI - Survey of patients' knowledge of nosocomial infections. AB - A survey of discharged patients revealed that 62% of respondents were aware of the risk of nosocomial infection before they received the survey. Of the respondents 12.4% said they had suffered from a nosocomial infection; 70% were concerned about their risk of acquiring a nosocomial infection in the future; 83% believed nosocomial infections were preventable; 69% said the risk of acquiring a nosocomial infection was never explained to them during hospitalization; and 62% were dissatisfied with the information that hospitals and the medical community provided concerning the risk of nosocomial infections. Fifty-seven percent were willing to pay an extra $7.14 mean per diem charge to enhance the hospital's infection control program if this payment would lower their risk of infection. This survey suggests that the subset of responding patients want to know more about the risk of nosocomial infections, and they are willing to pay for more resources to be channeled into effective infection control programs. PMID- 2923313 TI - Survey of techniques used for sterilization of facial implants. AB - Policies need to be developed in each institution to ensure that OR personnel alert the CSS when implants are sent to CSS for sterilization so that a spore test can be processed with each implant regardless of the method of sterilization (steam, gas, or other). Implants should be quarantined for a 48-hour negative test result when possible. It is advisable to keep a log in CSS for items that require premature release with prior notification of the physician. In situations when implants and materials must be customized during surgery, OR personnel may sterilize the unwrapped implants and materials with a spore test. Under special circumstances, such materials may be released for use before obtaining the results of the 48-hour spore test, if the special circumstances are recorded in a log in the OR. If a spore test is subsequently found to show positive results, the physician and infection control personnel should be notified by telephone by OR personnel. Opposition to these policies in institutions that have implemented them has gradually diminished as surgeons have become used to the requirements and realize the rationale. OR nurses and infection control personnel need to understand that the procedures constitute safer patient care practices and that they are in full compliance with CDC guidelines. PMID- 2923314 TI - AIDS: problem solving in infection control. Universal precautions: Part 2. PMID- 2923315 TI - Threat of AIDS: relationship between knowledge and attitudes. PMID- 2923316 TI - Compliance with needle disposal policies. PMID- 2923317 TI - Force systems from an ideal arch--large deflection considerations. AB - A sophisticated mathematical simulation is presented which allows for the consideration of large activations in orthodontic appliances and their effect upon the resulting force systems which are delivered to teeth. Effects of bracket/wire interaction are studied using this new tool. Previous studies of force systems from an ideal arch were redone with the new analysis in which the wire was either rigidly restrained or free to slide. The restraint of the wire produced large mesio-distal forces and increased the magnitude of the moments on each bracket. If the wire is free to slide, both large deflection and small deflection solutions give similar results. The relative force system M1/M2 fundamentally held true with large deflections and restraint; however, some differences were noted. The significance of allowing wire to slide in the bracket is discussed. PMID- 2923318 TI - Force distribution comparisons of various retraction archwires. AB - A photoelastic study comparing the effects of the activations of three retraction arch wires used in orthodontic therapy. Schematic representations of space consolidations, intrusion and root torque are illustrated. PMID- 2923319 TI - Mandibular rotation and lower face height indicators. AB - Lower face height indicators and mandibular rotation are assessed at 7 and 12 years of age in a sample of 46 children, comparing the corpus axis and mandibular plane as indicators of change in mandibular position. The parameters involving the mandibular plane consistently show higher correlations. PMID- 2923320 TI - Correlations among craniofacial angles and dimensions in Class I and Class II malocclusions. AB - In normal and Class I malocclusions, ramus and mandibular angles are found to correlate most strongly with cranial base dimensions rather than angles, whereas in Class II malocclusions these angles tend to relate more closely to the cranial base angles. PMID- 2923321 TI - Rotational effects of S-N on the dentoskeletal pattern within the range of normal. AB - The range of orientation of SN in relation to the craniofacial centroid line in a Class I sample with "acceptable" profiles is divided into three groups for comparison with facial dentoskeletal structures and evaluation of the adaptations among them. This manuscript was originally submitted September, 1986. PMID- 2923323 TI - Aligning, leveling, and torque control--a pilot study. AB - Aligning, leveling, and anterior torque control of teeth from the onset of treatment is suggested with thermal ni-ti rectangular low stiffness wires. Before and after superimpositions show the degree that torque control was achieved on four clinical patients. PMID- 2923322 TI - Stability of maxillary surgery in openbite versus nonopenbite malocclusions. AB - Lateral cephalometric radiographs were evaluated to determine the posttreatment stability of 66 patients treated with LeFort I osteotomies to reposition their maxillae superiorly. The sample was divided into three groups based on the degree of pretreatment overbite: openbite subsample--no incisal overlap; overlap subsample--incisal overlap and no incisal contact; contact subsample--incisal overlap with incisal contact. The cephalograms were superimposed and linear measurements were made at each interval (pretreatment, posttreatment, and at least one year posttreatment). The results clearly show that the three subsamples reacted differently during the posttreatment interval. 42.9 percent of the subsample with pretreatment openbite showed a significant increase in facial height, significant eruption of maxillary molars, and a significant decrease in overbite. 28.6 percent of the openbite subsample and 16.7 percent of the overlap subsample showed a significant increase in facial height, significant eruption of maxillary incisors, and no change in overbite. The contact subsample had no significant posttreatment changes. Possible reasons for the posttreatment instability in the openbite subsample are proposed. PMID- 2923324 TI - Case report. Presence of fibrous dysplasia affects the treatment approach for a 28-year old female patient. PMID- 2923325 TI - Pulmonary hemorrhage in a young infant. PMID- 2923326 TI - Comparison between refractoriness after distilled water-induced asthma and exercise-induced asthma. AB - Inhalation of distilled water (DW) frequently induces bronchoconstriction in asthmatic patients. We compared the degree of refractoriness to repeated inhalation of DW to that of repeated exercise challenge in 14 asthmatics. Refractoriness was seen following inhalation of DW. The maximum drop in FEV1 (% of predicted) following the first challenge was 31 +/- 13% and the maximal drop following the second challenge was 18 +/- 9% (P less than .01). The pattern of the airway response seen during 45 minutes following repeated inhalation of DW and exercise was similar. Cross refractoriness was also seen when inhalation of DW followed exercise challenge. It was concluded that both stimuli probably share a common mechanism of action on the airway. PMID- 2923327 TI - Pine nut allergy in perspective. AB - Anaphylaxis and other acute allergic reactions following the ingestion of pine- or pinon--nuts are documented and reviewed in perspective. Systemic allergic reactions to other relatively uncommon or "exotic" foods are also considered. Although hypersensitivity to more than one type of "nuts" is reported by some individuals, no significant cross-reactivity between any of these, or between pine pollen, pine resin, and pine nuts has been demonstrated. PMID- 2923328 TI - Two cases of aspirin-intolerant asthma whose leukocytes demonstrated hypersensitivity to sulpyrin. AB - Two cases of aspirin-intolerant asthma whose polymorphonuclear leukocytes demonstrated hypersensitivity to sulpyrin in vitro were reported. The patients were 14- and 15-year-old girls. Aspirin and sulpyrin intolerance were confirmed by aspirin oral provocation test and bronchial sulpyrin inhalation provocation test. In those intolerant patients, preincubation of polymorphonuclear leukocytes with sulpyrin enhanced the calcium ionophore A23187-induced leukotriene C4 production as compared with those of healthy adults and aspirin-tolerant asthma. PMID- 2923329 TI - The role of food allergy on school behavior and achievement. PMID- 2923331 TI - Prehospital intravenous line placement: a prospective study. AB - We prospectively measured the on-scene time, transport time, and IV line starting time for 97 patients receiving paramedic care in an urban region during an 18 month period. The overall success rate for IV line placement was 91%, and the average successful IV line starting time was 2.5 minutes. En route IV line attempts had similar success rates and starting times. The on-scene IV line starting times were shorter than the transport times in 86% of patients. We conclude that definitive IV line medical therapy, when available, can be delivered effectively by paramedics at the scene. We also conclude that en route IV line placement is feasible in trauma victims. PMID- 2923330 TI - Reperfusion arrhythmia: myth or reality? AB - Early reports of "reperfusion arrhythmia" after experimental temporary coronary occlusion raised concern that these arrhythmias, particularly ventricular fibrillation and ventricular tachycardia, might occur in association with reperfusion of an occluded coronary vessel during thrombolysis. Such an occurrence could increase the risk of transfer of such patients. To provide a more definitive answer to this question, we reviewed hospital and transfer records for all patients with acute myocardial infarction transferred by our critical care transfer service between January 1, 1985, and November 30, 1987, noting the occurrence of five types of arrhythmia: ventricular fibrillation, ventricular tachycardia, premature ventricular contractions, bradycardia, and atrioventricular block, both before and during transfer. Five hundred patients with acute myocardial infarction less than 48 hours old were transferred during this period. Two hundred twenty-five patients received thrombolytic therapy; 270 did not (five unknown). The type of acute myocardial infarction was known for 471 patients: 192 were anterior, 203 were inferior, and 76 were lateral. There were no deaths during transfer. Overall survival through hospitalization was 91%. The incidence of arrhythmia was 36% before transport and 12% during transport. There was no difference in arrhythmias overall, or with respect to any of the five arrhythmias specified, between patients who received thrombolytic therapy before and during transport and those who did not. Reperfusion arrhythmia does not appear to be a clinically significant entity during the transport of patients who are receiving IV thrombolytic therapy. PMID- 2923332 TI - Pediatric critical care transport: is a physician always needed on the team? AB - We conducted a retrospective study of the interventions performed by physicians in 191 transfers by our pediatric critical care transport team. Currently, the team always includes a pediatrician or pediatric resident, a pediatric emergency department nurse, and a pediatric respiratory therapist. Procedures performed during transport were divided into those done only by physicians in our institution and those also performed by nurses or respiratory therapists. Physician procedures were performed in 9% of transports. Medications given during transport were divided into three categories. Category 1 included drugs used only in our ICU and therefore with a physician present. Category 2 drugs were usually given in the ICU but were occasionally administered on the floor with close physician involvement. Category 3 included drugs routinely given on the floor with rare physician involvement. Category 1 drugs were required on 19% of transports, category 2 was the highest level used on 15%, and category 3 drugs alone were used on 20%. No medications were administered on 46% of transports. At the completion of each trip, the transport physician was asked if he believed the transport would have been successful without a physician but with an experienced pediatric ED nurse and respiratory therapist. The answer was "yes" in 46% of the cases (n = 166), "no" in 43%, and "unsure" in 11%. In 91% of the transports, no procedures were performed that required a physician. In 66%, no medications were used that required physician presence. In at least 46%, the physician believed his expertise was not required for the transport's success.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2923333 TI - Lack of effectiveness of lidocaine for sustained, wide QRS complex tachycardia. AB - Records of 31 episodes of sustained, wide QRS complex tachycardia treated with IV boluses of lidocaine in 20 consecutive patients were reviewed. Most of the episodes were managed in the emergency department. Patient ages ranged from 18 to 91 years (mean +/- SD, 64 +/- 17), and 17 of 20 were men. All but three had coronary artery disease. Although 19 of 20 patients were admitted with a diagnosis of "rule out acute myocardial infarction," only two had this diagnosis confirmed. Seventeen patients had ventricular tachycardia, and three had wide QRS complex supraventricular tachycardia. Patients were given one to three boluses of lidocaine totaling 75 to 400 mg (127 +/- 64 mg). Termination of the tachycardia was temporally related to lidocaine administration in only six of 31 episodes (19%) occurring in five of 20 patients. In three of these five patients, lidocaine was given again for a recurrence of the tachycardia and was ineffective. A similarly low efficacy was seen in 20 episodes initially managed in the hospital compared with 11 episodes initially managed by paramedics. Thus, although lidocaine is widely considered the drug therapy of first choice for sustained wide QRS complex tachycardia, it was not usually effective in our study. Patients presenting to the ED with this rhythm disturbance rarely prove to have acute myocardial infarction. Although this small retrospective study should not be the basis for a change in standard medical practice, the recommendation of lidocaine as initial therapy for such patients should be reexamined. PMID- 2923334 TI - The usefulness of serum electrolytes in the evaluation of acute adult gastroenteritis. AB - Acute gastrointestinal disorders are among the most common problems encountered by the emergency physician. Serum electrolytes are commonly ordered in the evaluation of patients with gastroenteritis. We retrospectively reviewed the charts of all 281 patients with a discharge diagnosis of acute gastroenteritis seen in our emergency department during a recent six-month period. Electrolytes were ordered on 207 of these patients, and the time spent in the ED was three to four times longer for patients on whom electrolytes were ordered. Of these 207, 24 (11%) had electrolyte abnormalities, but only two (1%) had clinically significant electrolyte abnormalities, which were defined as values that affected patient treatment or disposition. On presentation, 56 patients (27%) had orthostatic vital sign changes (defined as a pulse increase of 30 or more on standing). Five (10%) had electrolyte abnormalities. None of the abnormalities were clinically significant. Eleven patients (5%) were hospitalized. One patient had electrolyte abnormalities that were not the cause of hospitalization. No patients with uncomplicated gastroenteritis alone had clinically significant electrolyte abnormalities. We conclude that there is no justification for the routine ordering of serum electrolytes on the adult patient with acute gastroenteritis. PMID- 2923335 TI - On-line medical command in theory and practice. AB - Paramedics are often required to use on-line medical command (OLMC) when they provide advanced life support. We evaluated the efficacy of OLMC use under this broad patient inclusion rule and limited paramedic discretion. OLMC was associated with an average of an eight-minute longer on-scene time, and an infrequent rate of physician-directed deviation from written treatment protocols (3.7% of all OLMC calls). Of the system's advanced life support patients, 6.1% experienced changes in their prehospital health status, reflected in changes in the patient's level of consciousness. OLMC use was associated with improved health status in 5.5% of patients compared with 3.2% for those treated without OLMC (P = .1). The health status of 1.3% of the patients treated with OLMC deteriorated. This was not significantly different from the 1.1% of patients treated without OLMC whose status deteriorated. We suggest that targeted OLMC use with expanded paramedic discretion may improve the efficacy of OLMC. Further controlled comparative studies of OLMC efficacy under targeted OLMC use versus broad patient inclusion rules are needed. PMID- 2923336 TI - Access to emergency departments: a survey of HMO policies. AB - An unresolved question related to the practice of health maintenance organizations' (HMOs) controlling access to medical care is whether such screening of patients seeking emergency department treatment impairs efficient patient care or endangers patients. A preliminary study was undertaken to determine whether so-called gatekeeping of access to EDs was common practice. Medical directors of HMOs in 39 states and the District of Columbia were surveyed by a mail questionnaire to assess policies regarding ED access. There were 98 (80.3%) respondents to 122 questionnaires, representing 26% of all federally qualified HMOs in the United States. Of the 98 respondents, 90 (92%) used the distinctions "life-threatening" and "nonlife-threatening" in defining their ED access policies. In life-threatening situations, members were permitted to go to any hospital without calling the gatekeeper first. In nonlife-threatening situations 78 of 98 (80%) required that permission be obtained prior to an ED visit. Most required a telephone call; nonphysicians could act as gatekeepers in 46 of 78 (59%). Thirty-nine percent of the 98 respondents limited their members to using the EDs of certain hospitals only. Ninety-four of 98 (96%) reviewed all ED visits prior to making any payment. We discuss here the implications of these gatekeeping policies. PMID- 2923337 TI - Emergency department telephone advice. AB - Emergency department personnel are frequently asked to give advice to members of the community who telephone for advice or information about a wide variety of medical problems. A study was designed to determine the consistency and accuracy of directions given to adults who call EDs seeking advice about a problem. Forty six EDs were selected and telephoned for advice by a research assistant who presented a scenario that could have reasonably been interpreted as a patient experiencing myocardial ischemia. Nine percent of the calls were answered and managed only by ED unit secretaries. Fifty-six percent of the respondents failed to ask the caller any questions about the patient or the chief complaint. Only four ED respondents instructed the caller to call 911 and have the patient brought to the ED. The data suggest that telephone advice given by some EDs is nonstandardized and may be inadequate to the point of jeopardizing the welfare of the caller. PMID- 2923338 TI - Vital records in the development of injury control research. AB - Most of the resources of the emergency physician are devoted to persons already injured, with little emphasis on prevention. Analyses of state and local injury statistics are necessary to identify local prevention needs in order to set program priorities. We discuss an example, an analysis of statewide injury fatalities identified through the Illinois Vital Records database. The overall death rate for injuries in illinois was lower than that found for the United States. However, the need for research on several high-risk age groups for certain injuries was identified. Most notably, the homicide rate for those 15 to 24 years old was 140% of the national rate. Other specific nonwhite age groups were overrepresented in poisoning, fire, and firearm deaths, while specific white age groups were overrepresented in suicide, fall, and drowning deaths. The research regarding the etiologies of these injuries and the formulation and evaluation of prevention strategies based on this research must be interdisciplinary. The emergency physician is in a unique position to serve as a member of such an interdisciplinary injury control team, but currently there is little emphasis on or training for this role. PMID- 2923339 TI - Pacemaker function during helicopter transport. AB - A 71-year-old man had an increased pacemaker firing rate during helicopter transport. The increased rate, which resolved as soon as the engines were shut down, was thought to be due to the vibrations of the helicopter. We discuss the effect of vibration and electromagnetic force generated during helicopter transport on pacemakers. As the number of patients transported by air ambulances increases, the potential sequela must be recognized. PMID- 2923340 TI - The emergency management of a medicinal leech bite. AB - Leeches have been used as a medicinal remedy for years untold. Recently, there appears to have been a resurgence in the use of the medicinal leech, Hirudo medicinalis. Presented is the case of a patient who called the emergency department for advice concerning the management of a bleeding leech bite. We discuss briefly the pharmacologically active salivary contents of the leech and an approach to the emergency therapy of a medicinal leech bite. PMID- 2923341 TI - For whom the (phone) bell tolls. PMID- 2923342 TI - Bystander CPR--discouragement or reaffirmation? PMID- 2923343 TI - ABEM & critical care. PMID- 2923344 TI - Digital rectal message for PSVT. PMID- 2923345 TI - The data on HMO patients with AMI. PMID- 2923346 TI - Trauma in pregnancy. PMID- 2923347 TI - Evaluation by TC-99m leukocyte scan. PMID- 2923348 TI - Education adapts to meet challenges. PMID- 2923349 TI - Women cite child care as vital to family. PMID- 2923350 TI - ANA researches career center plan. PMID- 2923351 TI - ANA narrows focus, balances budget. PMID- 2923353 TI - Responding to the natural direction of change: nursing's educational and practice agenda. PMID- 2923352 TI - Keep quality of education, expectations high. PMID- 2923354 TI - North Dakota educates under new rules. PMID- 2923356 TI - Respiratory health of a population living downwind from natural gas refineries. AB - Since 1958 there has been a perception of excess illness in a rural Canadian population living downwind from two natural gas refineries, the emissions of which contain mostly sulfur dioxide but also hydrogen sulfide. To determine if there was an excess of adverse health outcomes in the population exposed (defined by place of residence), a health survey was undertaken in 1985 in this area and in one unexposed to emissions but demographically similar. Participation was 92% from both the exposed population (n = 2,157) and a representative sample (n = 839) of the main reference population. More respiratory symptoms were reported in the exposed group than in the non-exposed group among those 5 to 13 yrs of age (28% versus 18%) and among never-smokers greater than or equal to 14 yrs of age (35% versus 24%). FEV1, FVC, and FEV1/FVC were similar in both areas. Dichotomizing the level of exposure (high, low) within the exposed area revealed a trend in the high exposure area toward increased respiratory symptoms in the younger age group (39% versus 24%), but decreased symptoms in the older age group (33% versus 36% among never-smokers). FEV1 was similar between the two areas. The excess of respiratory symptoms in the exposed area unassociated with impaired spirometric values would be compatible with increased awareness of health or a small biologic environmental effect. PMID- 2923355 TI - Effects of inhalable particles on respiratory health of children. AB - Results are presented from a second cross-sectional assessment of the association of air pollution with chronic respiratory health of children participating in the Six Cities Study of Air Pollution and Health. Air pollution measurements collected at quality-controlled monitoring stations included total suspended particulates (TSP), particulate matter less than 15 microns (PM15) and 2.5 microns (PM2.5) aerodynamic diameter, fine fraction aerosol sulfate (FSO4), SO2, O3, and No2. Reported rates of chronic cough, bronchitis, and chest illness during the 1980-1981 school year were positively associated with all measures of particulate pollution (TSP, PM15, PM2.5, and FSO4) and positively but less strongly associated with concentrations of two of the gases (SO2 and NO2). Frequency of earache also tended to be associated with particulate concentrations, but no associations were found with asthma, persistent wheeze, hay fever, or nonrespiratory illness. No associations were found between pollutant concentrations and any of the pulmonary function measures considered (FVC, FEV1, FEV0.75, and MMEF). Children with a history of wheeze or asthma had a much higher prevalence of respiratory symptoms, and there was some evidence that the association between air pollutant concentrations and symptom rates was stronger among children with these markers for hyperreactive airways. These data provide further evidence that rates of respiratory illnesses and symptoms are elevated among children living in cities with high particulate pollution. They also suggest that children with hyperreactive airways may be particularly susceptible to other respiratory symptoms when exposed to these pollutants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2923357 TI - Quantitative sputum cytologic findings in 109 nonsmokers. AB - While sputum cytologic findings associated with cigarette smoking have been described, little information is available regarding nonsmokers for comparative analysis. Over a 3-month period, our cytopathology laboratory examined 3-day pooled sputa from 109 never smokers. Eighty-five percent were able to produce satisfactory results without recourse to induction. Ninety of 93 (97%) individuals had negative or reactive sputum cytologic findings. No carcinoma was identified. Two cases showed metaplastic changes and one case revealed dysplasia but all were from symptomatic never smokers. Eight components of stimulation of bronchial epithelium were microscopically quantified on each case and the mean values of each were calculated to produce a profile of an asymptomatic never smoker. PMID- 2923358 TI - Increased alveolar plasminogen activator in early asbestosis. AB - Alveolar macrophage-derived plasminogen activator (PA) activity is decreased in some chronic interstitial lung diseases such as idiopathic pulmonary fibrosis and sarcoidosis but increased in experimental models of acute alveolitis. Although asbestos fibers can stimulate alveolar macrophages (AM) to release PA in vitro, the effect of chronic asbestos exposure of the lower respiratory tract on lung PA activity remains unknown. The present study was designed to evaluate PA activity of alveolar macrophages and bronchoalveolar lavage (BAL) fluid in asbestos exposed sheep and asbestos workers. Forty-three sheep were exposed to either 100 mg UICC chrysotile B asbestos in 100 ml phosphate-buffered saline (PBS) or to 100 ml PBS by tracheal infusion every 2 wk for 18 months. At Month 18, chest roentgenograms were analyzed and alveolar macrophage and extracellular fluid PA activity were measured in samples obtained by BAL. Alveolar macrophage PA activity was increased in the asbestos-exposed sheep compared to control sheep (87.2 +/- 17.3 versus 41.1 +/- 7.2 U/10(5) AM-24 h, p less than 0.05) as was the BAL fluid PA activity (674.9 +/- 168.4 versus 81.3 +/- 19.7 U/mg alb-24 h, p less than 0.01). Among the asbestos-exposed sheep, 10 had normal chest roentgenograms (Group SA) and 15 had irregular interstitial opacities (Group SB). Strikingly, whereas Group SA did not differ from the control group in BAL cellularity or PA activity, Group SB had marked increases in alveolar macrophages (p less than 0.005), AM PA activity (p less than 0.02), and BAL PA activity (p less than 0.001) compared to the control group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2923359 TI - Maximal expiratory and inspiratory flow-volume curves in Parkinson's disease. AB - In order to investigate the type and degree of upper airway obstruction (UAO) in a group of patients with Parkinson's disease in different stages of the disease, we obtained maximal expiratory and inspiratory flow-volume (MEFV and MIFV) curves and maximal static mouth pressures. The clinical disability was indicated by a Hoehn-Yahr (H-Y) scale, ranging from III to V, and a more continuous Northwestern University Disability Scale (NUDS), ranging from zero to 50. Twelve patients were in H-Y Group III, and eleven and eight were in Groups IV and V, respectively. The pattern of the flow-volume curves was classified as either normal, or with superimposed regular or irregular oscillations (A), or with rounded-off and delayed expiratory peak appearance (B). Mean MEFV curves in Groups III and IV were not appreciably different from reference. In Group V, the mean curve showed a lower peak expiratory flow (PEF) and a more convex tail. Only the effort dependent variables PEF, peak inspiratory flow (PIF), and maximal mouth pressures at RV and TLC (PmTLC and PmRV) appeared to be significantly correlated with the NUDS index and decreased with increasing clinical disability. The mean values of those variables were also significantly different between the H-Y groups. The number of normal curves decreased from H-Y Group III to Group V. The contribution of A and B curves was relatively equal in the groups, with only a small number of A curves.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2923360 TI - Respiratory mechanics in acute quadriplegia. Lung and chest wall compliance and dimensional changes during respiratory maneuvers. AB - We measured lung and chest wall compliance as well as rib cage and abdominal dimensions in the supine position in five acute C4-7 quadriplegics. Studies were performed serially from 1 to 12 months after injury. Results were compared with those of control groups of chronic (greater than 1 yr after injury) quadriplegics and normal volunteers. We found that lung compliance was lower in acute and chronic quadriplegics (0.129 +/- 0.023 and 0.176 +/- 0.043 L/mm Hg, respectively) than in normal subjects (0.278 +/- 0.086 L/mm Hg) and that these changes apparently occurred within 1 month of injury. Specific lung compliance appeared to be reduced to a lesser degree, suggesting that the changes in lung compliance were partly due to reduced lung volumes and partly to altered mechanical properties of the lung. During respiratory maneuvers, abdomen and rib cage dimensional changes demonstrated rib cage distortion. This distortion was less severe in chronic than in acute quadriplegics. The improvement in chest wall stability was likely due to increased strength of cervical accessory muscles of respiration and improved coupling of the various rib cage elements in chronic quadriplegics. PMID- 2923361 TI - Transtracheal oxygen decreases inspired minute ventilation. AB - Although patients using transtracheal oxygen (TTO2) frequently report decreased dyspnea and improved exercise tolerance, the mechanism for these effects is unknown. We hypothesized that these patients might have decreased inspired minute ventilation (VI), and this might be one mechanism for their decreased dyspnea and improved exercise tolerance. The effects of TTO2 on VI were studied in seven patients with chronic hypoxemia; two had chronic obstructive lung disease and five had severe restrictive disorders. VI, exhaled minute ventilation (VE), respiratory rate (RR), tidal volume (VT), earlobe O2 saturation (O2 sat), and arterial blood gases were measured while patients received varying amounts of oxygen either transtracheally or by mouth to achieve equivalent degrees of oxygenation. With TTO2 VI was reduced compared to VI with mouth O2 at similar levels of PaO2. As TTO2 flow rate increased, VI decreased; at 6 L/min O2 delivered transtracheally, mean VI was reduced by 54 +/- 7.0%. Reduction in VI was due to decreased VT; RR did not change. To determine if air delivered transtracheally decreased VI, five patients were studied while receiving air transtracheally or by mouth. With transtracheal air, VI was significantly less than VI obtained while breathing air by mouth. We conclude that VI is decreased when oxygen or air is delivered directly into the trachea and that VI decreases as transtracheal flow increases. This effect is not due solely to changes in oxygenation. Decreased dyspnea and improved exercise tolerance in patients using TTO2 may be due to decreased VI and decreased inspiratory work of breathing. PMID- 2923362 TI - Pulmonary and extrapulmonary contributors to hypoxemia in liver cirrhosis. AB - To determine and to quantify the pulmonary and extrapulmonary contributors to hypoxemia in liver cirrhosis, we measured in 10 cirrhotics blood gases, P50, hemodynamics, ventilation, and the distribution of ventilation-perfusion ratios (VA/Q) using the multiple inert gas elimination technique. Seven patients had an arterial hypoxemia (PaO2 = 69 +/- 6 mm Hg, mean +/- SD), and three patients were normoxemic (PaO2 = 89 +/- 6 mm Hg). In each hypoxemic patient, the VA/Q distributions were characterized by the presence of low VA/Q units. A negative logarithmic correlation was found between the dispersion of the blood flow distribution and the arterial PO2. An acute inspiratory hypoxia (FIO2, 0.125) elicited an increase in pulmonary vascular resistance by 58.5% in the hypoxemic group and by 81.6% in the normoxemic one (p = NS between the two groups). The percent change in pulmonary vascular resistance induced by hypoxia was not correlated with the percent change in the dispersion of the blood flow distribution. A theoretical analysis showed that the mean arterial PO2 of 69 mm Hg of the hypoxemic group differed from a normal reference value of 96 mm Hg as a result of the combined effects of reduced hemoglobin (-4 mm Hg), increased P50 (+4 mm Hg), increased ventilation (+10 mm Hg), low VA/Q (-35 mm Hg), and true shunt (-2 mm Hg). These results show that the "hypoxemia of liver cirrhosis" is essentially caused by VA/Q mismatching, which is not explained by an abnormal hypoxic pulmonary vasoconstriction. PMID- 2923363 TI - The measurement of inspiratory muscle strength by sniff esophageal, nasopharyngeal, and mouth pressures. AB - Sniff esophageal pressure (Pes) is a useful measurement of global inspiratory muscle strength, although it does require passage of an esophageal balloon. We investigated the relationship between nasopharyngeal pressure (Pnp) or pressure within the mouth (Pmo) and Pes during a maximal sniff from FRC without a noseclip. We measured Pes, Pnp, and Pmo simultaneously in 10 normal volunteers, and in 12 patients with inspiratory muscle weakness. In both groups, Pnp and Pmo were slightly less but very close to Pes. In normal volunteers, the mean ratio Pnp/Pes was 0.92 +/- 0.006 (mean +/- SE) and Pmo/Pes was 0.95 +/- 0.006. Regression analysis showed Pes = 4.57 + 1.05 Pnp (r = 0.995, p less than 0.001) and Pes = 0.74 + 1.05 Pmo (r = 0.994, p less than 0.001). Similar relationships between Pnp, Pmo, and Pes were found over a wide range of pressures generated by submaximal sniffs in normal subjects. In patients, the mean ratio Pnp/Pes was 0.90 +/- 0.02 and Pmo/Pes was 0.87 +/- 0.03. Regression analysis showed Pes = 5.12 + 1.0 Pnp (r = 0.949, p less than 0.001) and Pes = 11.2 + 0.882 Pmo (r = 0.936, p less than 0.001). We conclude that Pnp and Pmo predict Pes during a maximal sniff in both normal subjects and in patients with inspiratory muscle weakness. Sniff Pnp and/or Pmo may provide a useful and less invasive method of measuring maximal inspiratory pressures during a sniff. PMID- 2923364 TI - Transdiaphragmatic twitch pressure. Effects of lung volume and chest wall shape. AB - The effect of lung volume and thoracoabdominal shape on the transdiaphragmatic twitch pressure (Pdit) amplitude was evaluated in six volunteers during airway occlusion. Twitch stimulation was applied through fine wire electrodes implanted near both phrenic nerves. Stimulations were tolerated with little discomfort and constant phrenic nerve responses were maintained for hours. At FRC the group mean Pdit was 31.4 cm H2O (range, 19 to 36 cm H2O), and its coefficient of variation ranged between 2 and 5% in individual subjects. At 1 L above FRC, the Pdit decreased a mean of 7.8 cm H2O (range, 2.8 to 11.9 cm H2O). This change was caused primarily by a decrease in esophageal pressure amplitude. The shape of the relaxed chest wall was altered by loading the rib cage with a force of 5 to 9 kg. Load and shape had little effect on Pdit independently of lung volume. Our modified technique of phrenic nerve stimulation through small wire electrodes is ideally suited for longitudinal intervention studies in patients. We conclude that the variability of Pdit with shape is small compared with its expected decrease with lung volume. PMID- 2923365 TI - Does the abnormal pattern of breathing in patients with interstitial lung disease persist in deep, non-rapid eye movement sleep? AB - Patients with interstitial lung disease (ILD) characteristically exhibit an increased ventilation and breathing frequency when awake. We wanted to see if these increases persisted during deep non-REM sleep. Using noninvasive techniques, we have quantified the pattern of breathing, arterial oxygen saturation, and transcutaneous PCO2 (PtcCO2) during standardized conditions of relaxed wakefulness and during Stage 4 (S4) sleep in eight patients with ILD and eight age-matched normal control subjects. The patients were given supplemental oxygen in order to prevent hypoxic ventilatory stimulation. The data were compared between the two groups during each of these states and also between states within each group. During wakefulness in the patients, respiratory frequency (f) and PtcCO2 were higher (p less than 0.001 and p less than 0.05, respectively) and inspiratory time (TI) and expiratory time (TE) were shorter (p less than 0.05 and p less than 0.001, respectively) than in the normal subjects. However, during S4 sleep, there were no significant differences between groups. Comparing wakefulness with S4 sleep: in the normal subjects during sleep, f and PtcCO2 were increased (p less than 0.01 and p less than 0.05, respectively), TE was shortened (p less than 0.01), and ventilation (VI) was unchanged. In contrast, in the patients, f decreased (p less than 0.001), TE lengthened (p less than 0.01), VI decreased (p less than 0.05), and the rise in PtcCO2 seen in the normal subjects during sleep did not occur.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2923366 TI - The role of atmospheric pressure variation in the development of spontaneous pneumothoraces. AB - It has been postulated that spontaneous pneumothoraces (SP) develop because of rupture of subpleural blebs, and that atmospheric pressure changes (delta AP) may be contributory. A 5-year retrospective analysis of SP admissions was carried out to determine if delta AP do play a role in SP development. Using a 36-yr record of hourly delta AP, a normative background for delta AP was constructed. A fall in AP below the fifth, or a rise above the ninety-fifth percentile during these time periods, was classed as "unusual." Atmospheric pressure changes in the 4 days prior to SP were analyzed. The expected frequency of SP occurring by chance, if no relationship to delta AP existed, was also calculated. A total of 192 cases of SP was analyzed. Traumatic pneumothoraces were excluded. The majority of cases (72%) had been exposed to at least one "unusual" delta AP in the 4 days prior to onset of symptoms. Among those with four or more "unusual" exposures, SP occurrence was significantly more frequent than expected by chance alone (p less than 10(-10]. A strong positive association between delta AP and SP was not found in all cases, as delta AP are unlikely to be the only causative factor for SP. This finding of a relationship with ambient pressure changes lends support to the theory that SP develop as a result of rupture of subpleural blebs. PMID- 2923367 TI - Low glucose and pH levels in malignant pleural effusions. Diagnostic significance and prognostic value in respect to pleurodesis. AB - In order to determine the diagnostic and prognostic significance of low pleural glucose and pH levels, we executed a prospective study of these parameters and cytologic yield in 77 cases of malignant pleural effusions diagnosed from 116 consecutive thoracoscopies. The extension of the neoplasms detected by thoracoscopy as well as the results of our attempts to carry out pleurodesis by talc were also studied. Pleural glucose levels were less than 60 mg/dl in 16 cases, and the cytologic yield was positive in 14 of these cases (87%). The glucose value rose above this level in 61 cases, and the cytology was positive in 30 cases (49%; p less than 0.006). A pH less than 7.30 was encountered in 18 cases and there were positive cytologic findings in 14 of these cases (78%). The pH was above 7.30 in 46 cases, and cytologic studies were positive in 22 cases (48%; p less than 0.03). There were ten cases in which both the glucose and pH levels were low, and the cytology was positive in 9 cases (90%), while there were 40 cases in which both the glucose and pH levels were high and cytologic yields of 20 of these cases were positive (50%; p less than 0.03). The extension of the lesions observed during thoracoscopy showed important differences as far as this related to the glucose levels (p less than 0.005), but this relationship as it concerned pH levels was even more significant (p less than 0.0002). The differences were also highly significant (p less than 0.003) when the glucose and pH were jointly considered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2923368 TI - Characteristics of upper airway chemoreflex prolonged apnea in human infants. AB - Water instilled into the pharynx of sleeping human infants elicits a range of chemoreflex responses that, occasionally, includes prolonged apnea (defined as absence of ventilation for at least 20 s, or for a shorter period if accompanied by bradycardia of less than or equal to 100 b.p.m. or cyanosis). To learn more about airway receptors mediating this prolonged apneic response and factors determining its occurrence, we examined the importance of stimulus location and associations between prolonged apnea, bradycardia, and upper airway responses. A total of 29 episodes of prolonged apnea were recorded after water stimulation in 12 infants. Bradycardia (HR less than 100) followed stimulus delivery but was always preceded by apnea and did not appear as an independent chemoreflex response. Behavioral arousal and prolonged apnea were not mutually exclusive responses and recovery from prolonged apnea was not always closely linked with arousal. Occurrence of prolonged apnea was greater after pharyngeal than nasal stimulation, and was frequently associated with coughing, but not with sneezing, suggesting that prolonged apnea is elicited from a sensory site close to, or the same as, one mediating cough. We conclude, using this water stimulus method, that the predominant receptors for chemoreflex-prolonged apnea are located in the pharynx or larynx rather than in the nose. PMID- 2923369 TI - The effects of prostaglandin E1 on lung injury complicating hyperdynamic sepsis in sheep. AB - We examined the hypothesis that PGE1 would reduce the severity of lung injury in sheep rendered septic by cecal ligation and perforation (CLP). Twenty-four to 30 h after CLP, septic lung injury was documented in 37 sheep because pulmonary lymph flow (Qlym) was increased above the baseline, nonseptic study (delta = +7.38 +/- 5.1 ml/h; p less than 0.05), whereas the lymph-to-plasma total protein ratios remained unchanged. During a subsequent 24-h "septic treatment" study period, Qlym continued to increase in an untreated study group (septic treatment minus septic delta = +10.24 +/- 4.9 ml/h; p less than 0.05), but not in sheep treated with PGE1 by continuous infusion at two doses, 1 micrograms/kg/h ("low dose": delta Qlym = -0.04 +/- 6.1 ml/h; p = NS) and 1 microgram/kg/min ("high dose": delta Qlym = -0.04 +/- 6.1 ml/h; p = NS. Mean pulmonary artery pressures (Ppa) increased in the untreated group during the septic treatment period (delta = +3.74 +/- 4.8 mm Hg; p less than 0.01), but not during PGE1 infusion in either of the low-dose (delta Ppa = -4.1 +/- 5.7 mm Hg; p less than 0.04) or the high dose (delta Ppa = -0.1 +/- 6.2 mm Hg; P = NS) groups. Unlike other study groups, the PaO2 fell in the high-dose PGE1 group during the septic treatment study (delta PaO2 = -15.0 +/- 9.6 mm Hg; p less than 0.01). During a study period of drug withdrawal 24 h after the septic-treatment period, Qlym again increased in the low-dose PGE1 group such that the untreated and PGE1 groups were no longer dissimilar.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2923370 TI - Accumulation of hyaluronan (hyaluronic acid) in the lung in adult respiratory distress syndrome. AB - The concentrations of hyaluronan (HA) were measured in bronchoalveolar lavage (BAL) fluid and serum from 12 patients with adult respiratory distress syndrome (ARDS). The median BAL fluid HA concentration was 353 micrograms/L, about six times higher than that seen in control patients (p less than 0.001). The median serum HA value was 619 micrograms/L, which was a 30-fold increase compared with that in the control patients (p less than 0.001). Another connective tissue component, type III procollagen peptide, was not recovered in significant amounts during lavage in patients with ARDS, but it appeared in the bloodstream in increased concentrations (p less than 0.001). Obtained recovery of HA during lavage of patients with ARDS cannot be explained by an enhanced passive leakage from the bloodstream because of increased alveolar-capillary permeability, but rather could reflect a mobilization of HA from lung interstitial tissue because of hydrostatic mechanisms. Alternatively, the appearance of HA in the alveolar space in ARDS might reflect an enhanced lung synthesis of HA. An increased HA production can possibly be mediated, directly or indirectly, by activated complement components, since a significant relationship was seen between increased plasma concentrations of C3a des Arg and BAL fluid HA (r = 0.61; p less than 0.05). The observed accumulation of HA in the small airways in ARDS may be expected to immobilize water and thereby contribute to the interstitial and alveolar edema. The inverse correlation (r = 0.71; p less than 0.01) seen between BAL fluid HA and pulmonary oxygenation index (PaO2/inspired oxygen fraction) supports such a hypothesis. PMID- 2923371 TI - The effect of inhaled naloxone on resting bronchial tone and exercise-induced asthma. AB - We wanted to determine whether 10 mg naloxone inhaled quantitatively could modulate the resting bronchial tone and respiratory response in exercise-induced asthma (EIA). In 11 asthmatic subjects, we measured specific airway conductance (SGaw) and forced expiratory flow (FEF) before and after the inhalation of naloxone or saline. In another 10 asthmatic subjects, we measured SGaw, FEF, and the ventilatory gas exchange, heart rate, and blood pressure responses produced by a treadmill exercise during 3 separate days: without any pretreatment (Day 1) or preceded by the inhalation of either 10 mg naloxone (Day 2) or saline (Day 3). We found that after 10 mg inhaled naloxone only one of 11 subjects bronchodilated, displaying an isolated, reproducible delta SGaw greater than 40% at 30 and 60 min. In the EIA protocol, the cardiopulmonary responses during exercise remained similar on all experimental days, but in seven of 10 subjects (all with %FEV1/FVC greater than or equal to 70% delta SGaw was -60 +/- 11%, + 1 +/- 40%, and -52 +/- 7% during no treatment, naloxone, and saline days, respectively (p less than 0.05). FEF changes were comparable on all days (p greater than 0.05). IN CONCLUSION: (1) consistent with the general role of endogenous opioids, these neurotransmitter/neuromodulators can modulate a stress related bronchoconstrictor response (EIA), but only very seldom the resting bronchial tone. (2) Naloxone does not blunt EIA through a decrease in the asthmogenic stimulus (i.e., ventilation) or airway caliber change, but presumably through competition with the endogenous opioids released during exercise. PMID- 2923372 TI - Occurrence, predictors, and consequences of adult asthma in NHANESI and follow-up survey. AB - Adult asthma has been the subject of relatively few epidemiologic studies; separation from chronic obstructive pulmonary disease (COPD) has been difficult. Utilizing a cohort of 14,404 subjects, 25 to 74 yr of age, from the First National Health and Nutrition Survey (NHANESI, 1971-75) traced by the NHANESI Epidemiologic Followup Survey (1982-84), we investigated prevalence, incidence, predictors, and consequences of adult asthma. Cases were based on subject reports of active doctor-diagnosed asthma (without COPD). Differentiation of asthma from COPD was partially successful, as suggested by correlations with smoking status and pulmonary symptoms, but was imperfect, as suggested by subsequent hospital experience. Followup interview underestimated interim hospital diagnosis of asthma by 28%. Prevalence of active asthma at NHANESI among U.S. adults was estimated at 2.6%, and followup incidence of new-onset asthma at 2.1/1,000/yr. Low income was the strongest independent predictor of asthma; the higher rates seen in blacks were largely explained by their lower income. Males and females had equal prevalence rates, but females had higher incidence rates. Asthma prevalence and incidence were independent of age and cigarette smoking. Asthmatics were often hospitalized with various lung conditions in the followup period, but unlike those with COPD, did not have a significantly increased risk of death. PMID- 2923373 TI - Mechanisms of hypoxemia in patients with status asthmaticus requiring mechanical ventilation. AB - Eight consecutive patients (mean +/- SD age, 43 +/- 11 yr) with acute severe asthma (status asthmaticus) requiring assisted ventilation were studied within the first 24 to 48 h of admission, at maintenance FIO2 and while breathing 100% O2, using the multiple inert gas elimination technique. Ventilation-perfusion (VA/Q) inequality was characterized by a marked bimodal blood flow distribution (perfusion to normal and low VA/Q populations) in all but two patients, with a mean of 27.6 +/- 12.3% of the total perfusion present in the low VA/Q ratio units (between 0.1 and 0.005). As a result, the dispersion of pulmonary blood flow distribution (log SDQ) was severely abnormal (mean, 1.65 +/- 0.28; normal range, 0.3 to 0.6). No patient had a substantial shunt (VA/Q = 0) (mean value, 1.5 +/- 2.3%). The ventilation distribution was never bimodal, but the dispersion of the ventilation distribution (log SDV) was moderately elevated (1.01 +/- 0.24). High VA/Q areas (ventilation to VA/Q units between 10 and 100) were generally absent. While breathing 100% O2, PaO2, PvO2, and PaCO2 significantly rose, as did shunt and blood flow dispersion. Patients with life-threatening acute severe asthma treated by mechanical ventilation show: (1) the most abnormal gas exchange characteristics of the VA/Q spectrum observed to date in human asthma but essentially the same pattern as in patients with less severe disease; (2) a high level of hypoxic pulmonary vascular response; (3) a significant amount of shunt while breathing 100% O2, suggesting the presence of absorption atelectasis or redistribution of blood flow. PMID- 2923374 TI - Surface IgA and Fc-alpha receptors on human alveolar macrophages from normal subjects and from patients with sarcoidosis. AB - Human alveolar macrophages (AM) obtained by bronchoalveolar lavage (BAL) were found to bear cytophilic IgA and Fc alpha-receptors (Fc alpha R) on their surface. The cytophilic IgA belongs to the IgA1 subclass, but unoccupied receptors can be saturated with either IgA1 or IgA2 molecules. Although both polymeric and monomeric forms could attach, binding was about 5-fold greater for the polymers. Both cytophilic IgA and Fc alpha R are sensitive to trypsin and disappear after 18 h of AM culture. An increase in cytophilic IgA was observed on AM from untreated patients with pulmonary sarcoidosis, but not on AM from steroid treated patients. A significant correlation was found between IgA levels in BAL and the percentage of AM with cytophilic IgA in normal subjects and in steroid treated sarcoid patients. However, no such relationship was seen among untreated patients. These data suggest that multiple factors may modulate AM surface receptors for IgA. Inflammatory events occurring in the lungs could alter receptor expression and perhaps be of significance in the immunophysiopathology of certain pulmonary diseases. PMID- 2923376 TI - Effect of heparin and warfarin on chronic hypoxic pulmonary hypertension and vascular remodeling in the guinea pig. AB - Chronic hypoxia produces pulmonary hypertension and pulmonary vascular remodeling. Heparin partially prevents the rise in right ventricular pressure and vascular remodeling in chronically hypoxic mice. To determine if this is due to the anticoagulant property of heparin or another property, we compared the effect of oral warfarin given at an anticoagulating dose (0.5 mg/kg/day) to heparin given by continuous infusion at a dose that does not prolong the partial thromboplastin time (PTT) (20 units/kg/h) on hypoxic pulmonary hypertension and vascular remodeling in the guinea pig. Normoxic control animals either untreated or treated with heparin or Coumadin were all alike in blood gases, pulmonary vascular resistance, right heart weights, and pulmonary histology. Hypoxia (10% 0(2) for 10 days) induced similar and significant increases in mean pulmonary artery (PA) pressure in both the hypoxic control and warfarin groups (19 +/- 1 mm Hg (mean +/- SEM) in both groups versus 11 +/- 0.1 mm Hg in the normoxic control group; p less than 0.05). Total pulmonary vascular resistance (TPR) was also increased from 0.041 +/- 0.002 in the normoxic control group to 0.087 +/- 0.007 and 0.071 +/- 0.003 mm Hg/ml/min/kg in the hypoxic control and warfarin groups, respectively (p less than 0.05). Whereas anticoagulation with warfarin did not protect the guinea pig from developing pulmonary hypertension, heparin markedly reduced PA and TPR (15 +/- 1 mm Hg and 0.052 +/- 0.002 mm Hg/ml/min/kg, respectively; p less than 0.05 versus hypoxic control or warfarin).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2923375 TI - Clearance of phosphatidylcholine and cholesterol from liposomes, liposomes loaded with metaproterenol, and rabbit surfactant from adult rabbit lungs. AB - Rabbits were given by tracheal instillation liposomes, liposomes carrying metaproterenol sulfate (MPS) and suspended in a MPS solution, rabbit surfactant, or rabbit surfactant suspended in a MPS solution. The lipid suspensions were labeled with [14C]cholesterol and [3H]phosphatidylcholine. The percent recoveries of the labels were measured over 24 h in alveolar wash, lung tissue after alveolar wash, and the total lungs. All clearance curves for both phosphatidylcholine and cholesterol from liposomes were the same in the presence or absence of MPS. Alveolar clearance curves for both labels from rabbit surfactant were the same; however, the surfactant-associated labels were cleared to the lung tissue more rapidly than were the liposome-derived labels. Despite different alveolar clearance curves, all clearance curves for cholesterol from the total lungs were similar at a rate of 20 to 30%/24 h of the injected labeled cholesterol. Phosphatidylcholine was cleared from the total lungs more rapidly, at rates from 35 to 56%/24 h. Although MPS did not change labeled liposomal lipid clearance, the beta-agonist increased surfactant lipid clearance. The different responses to beta-agonist and the different alveolar clearance curves indicated distinct alveolar-to-lung tissue metabolism for liposomal versus surfactant phosphatidylcholine and cholesterol, although overall lung clearance rates were similar. PMID- 2923377 TI - Human neutrophil elastase causes glycoconjugate release from the epithelial cell surface of hamster trachea in organ culture. AB - It is known that human neutrophil elastase (HNE) treatment of hamster tracheal explants causes the release of glycoconjugates, most of which appear to have the characteristics of mucus glycoproteins. This study was designed to determine the origin of HNE-induced glycoconjugate release from 1-day-old cultures of adult hamster trachea. After confirming that HNE treatment released glycoconjugates from cultures labeled with tritiated glucosamine, light microscopic autoradiograms and electron micrographs were prepared. Untreated cultures and cultures treated with inactivated HNE served as controls. HNE treatment caused a 40 to 50% decrease in the silver grain count on the external apical surfaces of secretory cells (p less than 0.05) and ciliated cells (p less than 0.01). Silver grain counts in secretory and ciliated cell cytoplasm, submucosa, and nontissue background were not significantly different from controls. The percentage of nongranulated secretory cells and the number of secretory granules in granulated secretory cells were similar in the HNE-treated and untreated controls. There was no evidence of constitutive release of radiolabeled glycoproteins, or of discharge of secretory granules from the secretory cells. We conclude that HNE releases mucins and other glycoconjugates from the external surfaces of both secretory and ciliated cells in tracheal organ culture. PMID- 2923378 TI - The pathophysiology of rhinitis. II. Assessment of the sources of protein in histamine-induced nasal secretions. AB - Nasal provocation tests were performed on nine atopic and 15 nonatopic subjects in order to assess the sources of protein in histamine-induced secretions and to examine the bilateral secretory response to unilaterally applied topical histamine (the nasonasal reflex). Nasal lavages were assayed for the following proteins: albumin, total protein, secretory IgA (sIgA), nonsecretory IgA (serum IgA), and total IgA. Histamine stimulation produced a profound ipsilateral protein secretion enriched in the serum proteins albumin and nonsecretory IgA. Histamine also produced a smaller contralateral protein secretion (about 15% as large as the ipsilateral response) which contained disproportionately elevated concentrations of the glandular protein sIgA. Topical pretreatment with chlorpheniramine (an H-1 antihistamine) completely abrogated the ipsilateral nasal secretory response to histamine. Nasal pretreatment with atropine (a muscarinic antagonist) had no significant effect on ipsilateral nasal secretion and did not alter the capacity of histamine to stimulate contralateral secretions (the nasonasal reflex). Histamine therefore stimulates secretion by both a direct action that increases plasma protein extravasation and by an indirect reflex mechanism that stimulates glandular secretion. PMID- 2923379 TI - Toxicity of eosinophil cationic proteins for guinea pig tracheal epithelium in vitro. AB - We tested the effects of four eosinophil granule cationic proteins: major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil peroxidase (EPO), and eosinophil-derived neurotoxin (EDN), on guinea pig tracheal epithelium in vitro. Examination by inverted microscopy revealed that MBP, both the form stabilized by alkylation of sulfhydryl groups as well as the native form of the molecule, ECP, EPO by itself, as well as EPO + H2O2 + halide, but not EDN, cause dose-related damage to the tracheal epithelium. The lowest concentrations of MBP and ECP causing damage were 10 and 100 micrograms/ml, respectively. In contrast, EDN, although biochemically similar to ECP, did not damage the tracheal epithelium in concentrations of up to 200 micrograms/ml. MBP caused exfoliation, as well as bleb formation and ciliostasis. EPO in the presence of the H2O2 producing enzyme glucose oxidase (GO), Cl-, 0.11 M, and iodide caused ciliostasis, bleb formation, and exfoliation of epithelial cells at concentrations as low as 1 U/ml (3.9 micrograms/ml). EPO + GO in the presence of Cl-, 0.11 M, alone or with Cl- and l-, 10(-4) M, or Cl- and Br-, 5 x 10(-5) M, were all toxic to epithelium. Surprisingly, EPO by itself caused partial ciliostasis, bleb formation, and exfoliation of epithelial cells in a dose related manner at concentrations as low as 10 to 30 U/ml (39 to 121 micrograms/ml). These results confirm prior observations showing the toxicity of MBP to tracheal epithelium and indicate that ECP and EPO alone, as well as EPO + GO + halide, cause damage. Thus, several eosinophil granule proteins are able to damage respiratory epithelium. PMID- 2923380 TI - Cellular events in the bronchi in mild asthma and after bronchial provocation. AB - We have undertaken detailed cellular and ultrastructural examination of bronchial biopsies and bronchial lavage fluid from allergic asthmatic patients in order to determine the nature and degree of the inflammatory processes in mild allergic asthma. Eight atopic asthmatic patients (mean PC20 histamine, 0.90 mg/ml) and four nonasthmatic control subjects underwent fiberoptic bronchoscopy. All asthmatic subjects were clinically stable for 2 wk prior to bronchoscopy and required either no treatment or inhaled albuterol alone. A single 50-ml bronchial wash was undertaken, followed by endobronchial biopsy of subcarinae. These procedures were repeated in the asthmatic subjects 18 h after bronchial provocation with allergen or methacholine. Subsequently, all subjects underwent bronchial reactivity testing with inhaled histamine. The clinical and physiologic data were not revealed to the pathologist interpreting the specimens. The asthmatic subjects shed a significantly greater number of epithelial cells into the lavage fluid than did the nonasthmatic subjects (7.23 versus 1.48 x 10(4)/ml, p = 0.048). There was a statistically significant inverse correlation between the lavage epithelial cell count and bronchial reactivity (rho = -0.64, p = 0.03). In the asthmatic subjects, but not in the control subjects, there was extensive deposition of collagen beneath the epithelial basement membrane, mast cell degranulation, and mucosal infiltration by eosinophils, which exhibited morphologic evidence of activation. Eosinophils, monocytes, and platelets were found in contact with the vascular endothelium, with emigration of eosinophils and monocytes in the asthmatic subjects. These changes were found irrespective of bronchial challenge with allergen. We conclude that allergic asthma is accompanied by extensive inflammatory changes in the airways, even in mild clinical and subclinical disease. PMID- 2923381 TI - Comparison of questionnaire and diary methods in acute childhood respiratory illness surveillance. AB - We compared two prospective survey methods, an interviewer-administered questionnaire and a daily diary, used concurrently to record acute respiratory illness experience over a 2-yr period in 422 children 5 to 11 yr of age from East Boston, Massachusetts. Respondents contributed more months of data with the questionnaire than with the diary method. Respiratory symptom and illness rates, as determined for the first year by each of the methods, were compared for 277 children who had less than 4 months of missing data. Respondents from families with more children tended to report a lower total respiratory illness rate by the diary than by the questionnaire method (p = 0.006). Although upper respiratory illness rates did not differ by method, lower respiratory illnesses were reported more frequently (p = 0.0001) by questionnaire than by diary. In the group of 49 children who were identified as having had greater than one lower respiratory illness, 25% of the illnesses reported as having been lower respiratory by questionnaire were reported as having been another form of respiratory illness by diary. For this group the ratio of 3:1 of boys to girls for the diary as compared with 1.5:1 for the questionnaire suggests the presence of reporting bias and no comparability of methods. Standardization of an acute respiratory illness questionnaire would provide greater opportunity than use of diaries for synthesis of prospective data from different epidemiologic studies. PMID- 2923382 TI - Bronchopulmonary dysplasia, undernutrition, and iron. PMID- 2923384 TI - Inspiratory muscle training with a pressure threshold breathing device in patients with chronic obstructive pulmonary disease. PMID- 2923383 TI - Clinical interpretation of airway response to a bronchodilator: epidemiologic considerations. PMID- 2923385 TI - Orthodeoxia as a sign of pulmonary fibrosis. PMID- 2923386 TI - High-level penicillin resistance among isolates of enterococci. Implications for treatment of enterococcal infections. AB - STUDY OBJECTIVE: To determine the extent and clinical significance of high-level penicillin-resistant Enterococcus faecium at our institution. DESIGN: Surveillance of clinical enterococcal isolates, in-vitro susceptibility and timed survival studies, and determination of antibiotic efficacy in an experimental model of enterococcal endocarditis. MEASUREMENTS AND MAIN RESULTS: For a 6-month period, 14% of enterococcal isolates (30 of 212) were identified as E. faecium. One third of the isolates were highly resistant to penicillin G (minimum inhibitory concentration [MIC], greater than or equal to 200 micrograms/mL) but did not produce beta-lactamase. The findings from in-vitro survival studies showed that this high-level resistance resulted in the loss of bactericidal activity normally observed when an aminoglycoside antibiotic agent is combined with penicillin. An experimental rat model of endocarditis provided in-vivo data that confirmed our in-vitro observations. After the rats received therapy for 72 hours, penicillin G either alone or in combination with gentamicin did not significantly decrease the numbers of enterococci in vegetations on heart valves compared with untreated controls (P = 0.62 and P = 0.58, respectively). CONCLUSIONS: Enterococcus faecium accounts for a notable proportion of clinical enterococcal isolates. Many strains from patients at our institution, as well as from patients at other institutions throughout the country, are highly resistant to penicillin. Because high-level penicillin resistance has important therapeutic implications, periodic surveillance and MIC testing of significant enterococcal isolates, especially E. faecium, are suggested. PMID- 2923387 TI - Importance of gonadal steroids to bone mass in men with hyperprolactinemic hypogonadism. AB - STUDY OBJECTIVE: To determine the effects of alteration of gonadal steroids on bone mass in men with hyperprolactinemic hypogonadism. DESIGN: Prospective survey of patients for a median period of 33 months. SETTING: Neuroendocrine clinical center of a referral-based university medical center. INTERVENTIONS: Reversal of hyperprolactinemia by bromocriptine therapy, transsphenoidal surgery, or radiation therapy, alone or in combination. PATIENTS: Consecutive sample of 20 male patients with prolactin-secreting pituitary tumors. MEASUREMENTS AND MAIN RESULTS: In patients who had a reversal of hyperprolactinemia and a restoration of gonadal function, a significant increase in bone density of the radial shaft was noted (mean +/- SE, 0.77 +/- 0.03 to 0.84 +/- 0.03 g/cm2; P less than or equal to 0.05). These patients also had a minimal change in the density of vertebral bone (109 +/- 9 to 115 +/- 10 mg of potassium phosphate, dibasic/cm3). Patients who remained hypogonadal despite the reversal of hyperprolactinemia had no change in radial (0.76 +/- 0.03 to 0.76 +/- 0.04 g/cm2) or vertebral bone density (105 +/- 10 to 103 +/- 9 mg of potassium phosphate, dibasic/cm3). There was a positive correlation between the change in testosterone level and the change in radial (r = 0.67, P less than or equal to 0.003) or vertebral bone density (r = 0.70, P less than or equal to 0.003). CONCLUSIONS: The reversal of hypogonadism, independent of the prolactin concentration, is associated with an improvement in bone mass. Our findings emphasize the importance of gonadal steroids in maintaining skeletal integrity in men. PMID- 2923388 TI - The two-period crossover design in medical research. AB - The crossover design has enjoyed popularity with many clinical researchers, but has been criticized by biostatisticians. The central problem is the inability to derive an unbiased estimate of the treatment effect when differences occur because of the different sequences in which treatments are applied. This problem can be traced to a deficiency of the logic of the crossover arrangement itself. Factors that can invalidate the findings of a crossover trial include nonuniform pharmacologic and psychologic carry-over effects, failure to return patients to their baseline state before the crossover, nonuniform changes in the patients over time, and the use of time-dependent response measures. When these problems can be anticipated, a parallel-groups design should be used instead of a crossover trial. PMID- 2923389 TI - Fulminant mumps myocarditis. PMID- 2923390 TI - Cocaine abuse and deep venous thrombosis. PMID- 2923391 TI - Screening for diabetes mellitus. PMID- 2923392 TI - Diagnosing the Sweet syndrome. PMID- 2923393 TI - Treatment of neurosyphilis. PMID- 2923394 TI - Human immunodeficiency virus (HIV) and aplastic anemia. PMID- 2923395 TI - Obstructive sleep apnea syndrome in sickle cell disease. AB - We present a series of 21 children with obstructive sleep apnea syndrome and sickle cell disease (SCD). Thirteen patients underwent adenotonsillectomy with resolution of symptoms and improvement in alveolar hypoventilation. Adenotonsillectomy involves significantly increased risks in patients with SCD. We present our protocol for management of these difficult surgical patients, including vigorous hydration and transfusion therapy. Polysomnography has proven valuable both in diagnosis and in identifying severely affected patients. Increased end tidal alveolar carbon dioxide during sleep has proven to be a significant predictor of disease, while oxygen saturation monitoring was shown to be unreliable. The incidence of adenotonsillar hypertrophy (ATH) in SCD appears increased and not related to infectious diseases. We suggest that ATH represents a part of the natural course of compensatory lymphoid tissue enlargement in children with SCD. PMID- 2923396 TI - Botulinum toxin for relief of bilateral abductor paralysis of the larynx: histologic study in an animal model. AB - We previously reported the effectiveness of botulinum toxin injections in the cricothyroid muscle under electromyographic guidance for lateralization of the true vocal cord in the mongrel dog. These additional experiments were performed to substantiate the effectiveness of botulinum toxin injections in laryngeal muscle to overcome airway obstruction produced by bilateral abductor vocal cord paralysis. A predetermined aliquot of the toxin was injected into the cricothyroid muscle of ten dogs, the duration of its effectiveness was noted, and repeated injections were given the animals. Biopsies of the injected muscles were obtained in three of the animals for routine histologic and electron microscopic studies. The effects of the toxin were recorded by cinelaryngoscopy and videotape documentation. In all the dogs, the true vocal cord was lateralized effectively and there was no morbidity, dysphagia, aspiration, or deaths. This study also confirms that the effects of the toxin in the canine larynx are spontaneously reversed and that multiple injections do not cause irreparable damage to the laryngeal muscles. PMID- 2923397 TI - Natural history of treated T1N0 squamous carcinoma of the glottis. AB - The records of 373 patients with T1N0 squamous carcinoma of the glottis were examined. Of these, 271 underwent initial hemilaryngectomy; 102 had full-course irradiation for cure. While the overall survival rates of the two initial therapies were similar, failure of the initial treatment modality was approximately twice as frequent in the irradiated patients (34.4%) as in the patients undergoing hemilaryngectomy (16.9%). The effect of this difference in initial failure rate on quality of life and on cost of overall therapy will be discussed. PMID- 2923398 TI - Effect of vocal fold augmentation on laryngeal vibration in simulated recurrent laryngeal nerve paralysis: a study of Teflon and Phonogel. AB - Flaccid laryngeal nerve paralysis may be treated by vocal fold augmentation with Teflon injection, which is successful to various degrees depending on the subjective interpretation of the patient or clinician. A new material, Phonogel, consisting of cross-linked bovine collagen, is available but not approved for human use in this area. Ten dogs were submitted to videostroboscopy, photoglottography, electroglottography, and acoustic analysis in the normal state, with stimulated recurrent laryngeal nerve paralysis, and with injection of either Teflon or Phonogel. A statistical comparison and the advantages and disadvantages of each material are discussed in relation to this study and its clinical use. PMID- 2923399 TI - Definitive radiotherapy in the management of stage I and II carcinomas of the glottis. AB - Definitive radiotherapy for early glottic carcinoma continues to offer excellent control and the advantage of voice preservation. In the 13 years from January 1972 through December 1984, there were 187 patients diagnosed with squamous cell carcinoma of the glottis at the University of Virginia Medical Center. One hundred forty-eight patients were treated with definitive radiotherapy as the initial management. The 3-year disease-free survival for the irradiated population was 93.6% in stage I and 75.5% in stage II. Twenty patients had recurrences following radiotherapy, and 13 of 20 were successfully surgically salvaged for an overall determinate survival of 100% in stage I and 85.7% in stage II at 3 years. These statistics are comparable to those from our previous 16-year review of 147 patients from 1956 through 1971. Factors of prognostic significance were persistent hoarseness after radiotherapy, impaired cord mobility, subglottic extension, and multiple sites of involvement in stage I. We conclude that definitive radiotherapy offers excellent survival and that a majority of the small number of treatment failures can be managed with surgical salvage. PMID- 2923400 TI - Oncocytic cyst of the larynx. PMID- 2923401 TI - Sinus histiocytosis with massive lymphadenopathy. AB - Sinus histiocytosis with massive lymphadenopathy is a lymphoreticular disorder of obscure pathogenesis with extranodal lesions and a variable clinical course. Clinical manifestations are most often in the head and neck, with 97% of patients showing cervical lymphadenopathy and a significant but lesser number having lesional infiltrates in the upper aerodigestive tracts, particularly the nasal cavity and salivary glands. PMID- 2923402 TI - Latissimus dorsi free flap for restoration of facial contour defects. AB - The treatment of facial asymmetries presents an aesthetic component of great importance. To correct facial contour defects, there are many therapeutic possibilities available, such as autologous tissue grafts and inorganic implants. The arrival of microsurgical techniques has improved the outlook for facial contour restoration. Among the tissues used are groin, escapular, and omentum flaps. This article introduces our experience with the latissimus dorsi free flap for the restoration of facial contour defects. Our experience is based on 7 patients affected with hemifacial microsomia and Romberg's disease. Operative planning, surgical procedure, and results are described. The use of the latissimus dorsi free flap is our procedure of choice for its greater adaptability in conforming to the shape of the defect, its long vascular pedicle, the abundance of available tissue, and minimal tendency to ptotic changes. At present we recommend this technique for replacement of soft tissue in severe defects of the face. PMID- 2923403 TI - Treatment of delayed union, nonunion, and malunion of the phalanges of the hand. AB - Nonunion occurs in less than 1% of phalangeal fractures. Despite this rarity we have accumulated a series of 14 proximal and middle phalangeal delayed unions, nonunions, and malunions. All patients but 1 were initially treated by a physician other than the senior author. All patients developed loss of active motion following their primary treatment. Secondary treatment was by open reduction and internal fixation with Kirschner wires. The mean and median total active motion before secondary treatment were 130 and 90 degrees, respectively. Following secondary treatment, the total active motion increased significantly (p less than 0.05) to a mean of 215 degrees and a median of 255 degrees. We recommend secondary treatment of delayed union, nonunion, and malunion of phalanges of the hand. Open reduction and internal fixation followed by early (two to three weeks) active motion leads to a significant improvement in finger function. PMID- 2923404 TI - Drug injection injuries of the upper extremity. AB - The increasing incidence of illicit intravenous drug abuse has reached epidemic proportions in western society. Although the accompanying infectious complications such as hepatitis and acquired immunodeficiency syndrome receive the most notoriety, injection injuries are causing an increasing number of problems. A retrospective review of patients requiring admission for acute or chronic drug injection injuries of the upper extremities was made at the Detroit Receiving Hospital from 1980 through 1985. The demographical, historical, physical, microbiological, and follow-up data were analyzed. The majority of the injuries involved subcutaneous injections into the hand with accompanying inflammatory or infectious complications. The bacteriological data revealed unique characteristics and did not reflect patterns expected from inoculation of normal skin flora. A treatment regimen based on the data is proposed. PMID- 2923405 TI - An effective cosmetic treatment for Ota's nevus. AB - The congenital facial melanocytic lesion Ota's nevus is reviewed, and an effective cosmetic treatment--sequential dry ice application and epidermal peeling combined with argon laser--is discussed. It is emphasized that Ota's nevus is not simply a dermal lesion and that patients should receive careful ophthalmological follow-up. PMID- 2923406 TI - Monomorphic adenoma of the parotid in a premature neonate. AB - We report the case of a monomorphic adenoma of the parotid in a neonate. Although solid tumors of the parotid are rare in the pediatric population, these lesions may develop in utero and present at any time after birth. A solid mass in the parotid must be considered malignant until proved otherwise regardless of the age of the patient. PMID- 2923407 TI - Striving for excellence in breast reconstruction: the salvage of poor results. AB - Poor results in breast reconstruction can often be salvaged by turning to alternative techniques when the original treatment strategy has not produced optimum results. To do this, the surgeon must be willing to admit to aesthetic failures and correct them. If this is done honestly and vigorously, the multiplicity of methods presently available can allow us to turn many of our failures into successes. Five patients are presented to illustrate these principles and suggest some specific strategies for improving mediocre or poor results. PMID- 2923408 TI - The extended temporoparietal fascia "non-free" flap. AB - The extended temporoparietal fascia flap is a logical variation of previously accepted extended free tissue transfers, which are unique in that the recipient and donor vessels are identical. This local scalp flap permits adequate distant ipsilateral skull coverage with minimal patient inconvenience. If desired, retrograde fascial perfusion from cephalad collaterals allows the completion of long interposition vein graft microanastomosis to the superficial temporal vessels before creating any recipient site defect without fear of flap warm ischemia time. Although the patient described had complications, the concept of the extended temporoparietal fascia flap has been proved to be an intriguing option for head and neck reconstruction. PMID- 2923409 TI - Sad pleats. AB - A surgical technique is presented for the correction or improvement of the unaesthetic pleat that arises from the commissures of the mouth and gives the patient a sad look. PMID- 2923410 TI - The role of external cranial fixation in simplifying scalp composite tissue transfer. AB - The use of external devices for cranial suspension or immobilization may facilitate the transfer of skin grafts or flaps needed for scalp coverage. Skull tongs are readily available in any trauma center. Following composite tissue transfer to the skull, skull tongs can prevent compromise of the microanastomoses or the flap itself by eliminating pressure or shear forces that might otherwise jeopardize these reconstructive efforts. PMID- 2923411 TI - Results of treatment of 48 ring avulsion injuries. AB - A retrospective study of 48 patients with ring avulsion injuries was performed. Patients were grouped according to severity of damage. Revascularization with interposition grafts was performed in all patients where indicated. In contrast to the experience of others, even class III lesions (total avulsion) were salvaged. PMID- 2923412 TI - Do children need routine preoperative blood tests and blood cross matching in orthopaedic practice? AB - A review of 315 children admitted for elective orthopaedic surgery on 346 occasions showed that 88.7% had a full blood count and 8.1% had serum urea and electrolyte estimations performed preoperatively. Two abnormal haemoglobin concentrations were found. One was known beforehand and the other clinically suspected. No other haematological or urea and electrolyte abnormality was found. On 82 occasions (23.7%) blood was cross matched. Blood was transfused on 15 occasions (18.3%) using 23% of cross matched blood. Routine preoperative full blood count, serum urea and electrolyte estimations are not indicated in healthy children. In our experience, only children who may need blood transfused postoperatively need a preoperative haemoglobin concentration estimation as a baseline. These are patients undergoing major spinal, pelvic girdle and upper femoral surgery. PMID- 2923413 TI - Imperforate anus in male children: a new operation of primary perineal rectourethroanoplasty. AB - From experience in managing 348 patients with imperforate anus and after considering the existing literature, there appeared to be the possibility of performing a safe primary correction of supralevator anorectal anomalies via a perineal approach in the neonatal period in males. A total of 39 patients have been treated by the new operation, and in 31 of these patients the operation was carried out at birth. With a stiff catheter in the urethra, via a horizontal 'H' shaped perineal incision and through the puborectalis sling, the rectum was mobilised and the fistula transfixed. The rectum was brought through the sling and sutured to the perineum so that perineal skin entered the new anal canal. In a few patients an abdominal approach was required at the same time. There were few postoperative complications. Subsequent X-rays showed good urethral and pelvic floor anatomy and function. Twenty-five of the babies are now over 2 years old. Of these, 84% are continent for solid faeces and 68% for liquid faeces. The perineal approach permits satisfactory identification of the puborectalis, rectum and fistula in most babies. Cutting the pelvic floor is not satisfactory. Introducing perineal skin into the anal canal is important. Early operation enables the child to learn to use its perineum. It is difficult to know whether the results in this series are attributable to the type of operation or its timing. PMID- 2923414 TI - Death from unsuspected colorectal cancer. AB - An analysis of all subjects undergoing autopsy in the Plymouth Health District over a 10-year period revealed 61 cases of unsuspected colorectal cancer. The carcinoma was the primary cause of death in 57 cases and surgical treatment for cure might have been possible in over one-half. The 61 subjects accounted for 4.1% of all cases of fatal colorectal cancer in this area. Examination by means of rectal digital palpation, rigid sigmoidoscopy and flexible sigmoidoscopy might have diagnosed 10, 24 and 41 carcinomas respectively. This study has demonstrated that a significant number of colorectal cancers remain undetected until after death. These cases should be included in future studies of colorectal cancer. PMID- 2923415 TI - Surgical intervention in severe acute pancreatitis: 476 cases in 20 years. AB - During a 20-year period 1967-86, 476 consecutive cases of severe acute pancreatitis were managed by one surgeon (GAK) and the role and results of surgical intervention in this group were reviewed. Of the 173 cases undergoing surgery, 77 were laparotomies for diagnosis, seven for the excision of necrotic pancreatic tissue and 89 for postpancreatitis complications (18 pseudocysts, 53 pancreatic abscesses, one large bowel perforation, 17 patients with persistent obstructive jaundice and one case of acute haemorrhage into a cyst causing obstructive jaundice). There were 50 deaths (11%) of whom 38 died early in the course of the disease, two died following total pancreatectomy and 10 died as a consequence of a pancreatic abscess. Based on this experience and on the current understanding of this condition, the place of surgery in severe acute pancreatitis is discussed briefly. PMID- 2923416 TI - Flexible urethroscopy: use in difficult male catheterisation. AB - A method is described for passing a urethral catheter down a guidewire which has been placed using a flexible cystoscope. PMID- 2923417 TI - Cholecystectomy and the development of colorectal neoplasia: a prospective study. AB - One hundred asymptomatic patients over 60 years of age who had cholecystectomy carried out at least 10 years earlier underwent double contrast barium enema and sigmoidoscopy. The incidence of colorectal adenomas and carcinomas was compared with age and sex matched controls undergoing routine post mortems. In the post cholecystectomy group 12% had tumours (8 adenomas greater than 1 cm in diameter, 4 carcinomas). In the control group 3% had tumours (3 adenomas); P = 0.02. This study confirms that patients with a history of cholecystectomy have an increased risk of developing colorectal adenomas and carcinomas. PMID- 2923419 TI - Acute traumatic haemarthrosis of the knee: expectant treatment or arthroscopy? AB - We have prospectively studied 50 patients with an acute traumatic haemarthrosis of the knee to investigate the place of examination under anaesthesia and arthroscopy in a district general hospital. There was a wide spectrum of injury to the knee, and 30% of patients required operative procedures. These important injuries could not be diagnosed reliably on initial clinical examination. We conclude that in the active patient under 35 years of age this policy allows prompt and appropriate treatment. PMID- 2923418 TI - Distal femoropopliteal bypass using a composite graft of PTFE and non-reversed saphenous vein. AB - The results of femoropopliteal bypass to the infragenicular popliteal artery, in the absence of suitable saphenous vein have, in the main, been disappointing. We present a new type of composite graft, for use when the distal anastomosis is below the knee, which avoids the potential problems of prosthetic graft alone. The graft consists of a proximal segment of 6 mm expanded PTFE (Gore-Tex; or Impra), anastomosed to transposed non-reversed autologous saphenous vein. Forty two patients were studied following unilateral, below knee composite femoropopliteal graft surgery for severe claudication or critical ischaemia. Pressure indices were calculated along with intraoperative flow rate, and all patients were followed up at regular intervals to assess graft patency. During the study period three patients died and graft occlusion occurred in a further eight. Analysis of the cumulative patency curve revealed that the majority of occlusions occurred in the first 3 months. The patency at 12 and 18 months was encouraging with values of 84% and 79% respectively. Comparison of pressure indices revealed a significant increase following surgery (P less than 0.001). The postoperative pressure index appeared to predict the grafts likely to occlude and the intraoperative flow rates mirrored a similar trend. Grafts which occluded had a significantly lower pressure index and flow rate (P less than 0.01, P less than 0.002, respectively). Our results suggest that for infragenicular femoropopliteal bypass grafting where full length in-situ vein graft is not possible; a composite graft using PTFE with non-reversed vein is a good alternative. PMID- 2923420 TI - Coeliac plexus block and cephalic spread of injectate. AB - Extensive cephalic spread of solution occurred in three out of seven cases studied during coeliac plexus blockade. Spread on to cardiac nerves and plexus may be a factor in hypotension following this procedure. Incremental dosage and careful screening is recommended. PMID- 2923421 TI - Age: an important factor in Barrett's oesophagus. AB - Thirty-one patients with a columnar lined oesophagus were studied. Half the patients were aged 70 years or over and only four patients were under 60 years of age at presentation. More than two-thirds of patients presented with a complication. Comparison by age showed a significant difference (P = 0.006) between the nine patients with uncomplicated Barrett's oesophagus (median age 64 years, range 28-79 years) and the 22 presenting with a complication (median age 75 years, range 36-89 years). This finding supports the view that the condition is acquired and that complications occur after injury resulting from prolonged reflux. Five patients (16%) had a carcinoma. Of the remaining 26 patients only seven (27%) underwent an antireflux procedure. Old age, associated medical problems and the effective control of symptoms by medical management (drugs and dilatation), reduced the need for surgery in this elderly population. PMID- 2923422 TI - Viable intraluminal tumour cells and local/regional tumour growth in experimental colon cancer. AB - To determine if viable intraluminal tumour cells can leak through a watertight anastomosis and cause local/regional (extraluminal) tumour growth, tumour cells were introduced 2 cm proximal to a colonic anastomosis following laparotomy in a Wistar/Furth rat colon cancer model. Local/regional tumour growth was observed in all rats except a sham anastomotic group. No intraluminal tumour growth was observed in either group. Viable intraluminal tumour cells cause local/regional tumour growth by leakage through a clinically intact anastomosis and may be an important cause of local/regional tumour growth in human colorectal cancer. PMID- 2923423 TI - Some clinical and technical aspects of circular stapled anastomoses of rectum and oesophagus. AB - A complete 8-year experience using the circular stapling instrument is described; 109 rectal and 59 oesophageal anastomoses were performed. Intra-operative problems included two suspected rectal leaks, damage to the tissues in two patients when using too large an instrument, cardiac arrythmias in one patient, precipitated by contact between the heart and the instrument, one instrument/operator failure, and inversion of the muscle layer was incomplete in three oesophageal anastomoses. Postoperative complications included two leaks, seven strictures, seven abscesses and one patient required reoperation. There were no deaths attributable to the use of the instrument or the method of anastomosis. The instrument has allowed satisfactory anastomoses to be performed in relatively inaccessible sites. PMID- 2923424 TI - Subcutaneous ketamine analgesia: postoperative analgesia using subcutaneous infusions of ketamine and morphine. AB - A series consisting of 32 women undergoing total abdominal hysterectomy received a standard narcotic-free anaesthetic. For the first 24 h postoperatively, eight were given the standard regimen of intramuscular morphine sulphate whilst the other three groups received continuous subcutaneous infusions of either morphine sulphate, ketamine hydrochloride or the two drugs combined. The amount of time they were pain free, the incidence of sleep and nausea, together with cardiovascular and respiratory changes were recorded. All three subcutaneous regimens produced significantly more pain-free readings than intramuscular morphine, but ketamine resulted in higher respiratory rates and less sleepiness. No patient reported psychomimetic side effects, but ketamine on its own produced feelings of malaise in three patients on the second postoperative day. Subcutaneous infusions provide better postoperative analgesia than intermittent intramuscular morphine. Ketamine on its own cannot be advocated, but combined with morphine it allows a single infusion rate to be used for all patients, decreasing the need for nursing and medical involvement. PMID- 2923425 TI - A randomised comparison of two postoperative fluid regimens. AB - Postoperative paralytic ileus follows all significant gastrointestinal surgery. Its duration is variable and has led to a variety of empirical and time-consuming oral fluid regimens. We have compared a traditional method of fluid administration with an unstructured, simpler, patient-determined approach. A series of 102 patients on a general surgical ward who required intravenous fluids on the day after surgery were randomised by a closed envelope system to one of two protocols and followed prospectively. Of these, 12 patients were erroneously randomised or unable to fulfil trial requirements. The first, 'regulated' group (n = 41) received hourly aliquots of oral fluid as determined by twice daily ward rounds according to ward routine. The second, 'unregulated' group (n = 49) were given a jug of water and instructed to drink as desired. Patients in the regulated group received less of their postoperative fluids by the oral route at all stages of recovery but there were no significant differences in the mean durations of intravenous therapy, nasogastric intubation or hospital stay. Postoperative complication and mortality rates were also similar. Patients who underwent gastric or duodenal procedures (n = 14) showed a similar pattern of results. We conclude that 'patient-determined' regulation of postoperative oral fluid intake is safe and effective and may greatly simplify ward management. PMID- 2923426 TI - Surgical glove failure rate. AB - Surgical gloves were collected after day-time operations for a 4-week period. Glove punctures were located by inflating each glove with compressed air and immersing the inflated glove in water. During the period of the study 681 surgical operations were performed. A total of 3790 gloves was collected, 334 gloves (8.8%) had perforations at the end of the surgical procedure. Defects occurred in one or more gloves in 32.0% of all operations. PMID- 2923427 TI - Transthoracic sympathectomy for palmar hyperhidrosis in children under 16 years of age. AB - Palmar hyperhidrosis can be a disabling condition in children. We report the results of transthoracic sympathectomy in 18 children aged 16 years or under. Follow-up, 1 to 11 years after surgery, revealed a high incidence of late sequelae, but these were not significant when compared to the primary condition. Transthoracic sympathectomy is recommended for children with severe palmar hyperhidrosis. PMID- 2923428 TI - Bupivacaine squirting. PMID- 2923429 TI - It's time to put some 'teeth' into solutions to the nursing shortage. PMID- 2923430 TI - Wrist arthroscopy. An ambulatory surgery procedure. AB - Because wrist arthroscopy is a relatively new procedure, at this point in time, it may be more valuable for diagnosis of wrist pain and mechanical disorders than for the treatment of them. It does, however, make the selection of proper surgical treatment more predictable. As more precise small joint instrumentation is developed for arthroscopic procedures, surgical treatment at the time of diagnosis becomes increasingly possible. The need for a second invasive procedure for many conditions may be eliminated, which in turn will benefit the patient. PMID- 2923432 TI - Congenital absence of the vagina. Surgical treatment and perioperative care. AB - A simple surgical technique is described for the correction of an absent vagina. It combines the positive features of the traditional approach of using a split thickness skin graft from the thigh or buttock applied on a plastic mold with the intermittent-pressure method of vaginal development. Since 1975, the new isograft technique has been performed on 15 patients at the Royal Women's Hospital, Melbourne, with excellent results and no complications. With one exception, satisfactory coitus productive of orgasm has occurred following the procedure. PMID- 2923431 TI - Electrical injuries. Considerations for the perioperative nurse. PMID- 2923433 TI - Clinical ladders. A plan that works. AB - Today is a challenging time for hospitals and nurse managers. Times of nursing shortage and the presence of more critically ill patients demand creative strategies. A clinical ladder helps managers hire and retain nurses. More importantly, it encourages perioperative nurses to advance their skills, making them better prepared to care for the seriously ill surgical patient in a safe, effective, and efficient manner. PMID- 2923434 TI - Nursing care documentation. Creating a perioperative nursing record. PMID- 2923435 TI - Medical device reporting. A pilot study of nurses. PMID- 2923436 TI - Recommended practices. Operating room environmental sanitation. AORN Recommended Practices Subcommittee. PMID- 2923437 TI - Recommended practices. Traffic patterns in the surgical suite. AORN Recommended Practices Subcommitte. PMID- 2923438 TI - Court actions regarding refusal of blood products. PMID- 2923439 TI - Particles from drill bit and metal suction tip friction distort magnetic resonance imaging. PMID- 2923440 TI - Is clinical experience for OR nursing managers necessary? PMID- 2923441 TI - State legislatures address reimbursement, uncompensated care, nurse practice act; Connecticut allows RN first assistants. PMID- 2923442 TI - Safety of pregnancy after discontinuation of isotretinoin. AB - Isotretinoin (13-cis-retinoic acid, Accutane) increases the risk of major congenital malformations in infants exposed to isotretinoin during pregnancy. However, there have been no epidemiologic reports to date on the effect of a subsequent pregnancy after discontinuation of isotretinoin. This article describes our analysis of pregnancy case reports from patients in whom conception occurred after isotretinoin treatment had been discontinued. Based on the 88 prospectively ascertained cases, the incidence rate of both spontaneous and missed abortions from all pregnancies was 9.1% (eight patients), and the incidence rate of congenital malformation among the live births was 5.0% (four patients). The incidence rates for both these outcomes were not significantly different from the rates reported for women of reproductive age in the general population. In addition, the malformations reported were not characteristic of retinoic acid-induced congenital anomalies. PMID- 2923443 TI - Granulomatous perioral dermatitis in children. AB - Five children, aged 3 to 11 years, developed a distinctive perioral, perinasal, and periorbital rash, consisting of tiny, closely spaced, flesh-colored "micronodules." Histopathologic examination in all five cases revealed upper dermal and perifollicular granulomas admixed with lymphocytes. There were no associated systemic abnormalities. The lesions resolved after months to years, leaving no scars. We propose that this condition is a form of perioral dermatitis with granulomatous histologic features, which can be distinguished from sarcoidosis and other facial eruptions in childhood both on clinical and histologic grounds. PMID- 2923444 TI - Blood vitamin and trace metal levels in epidermolysis bullosa. AB - Plasma or erythrocyte levels of ten nutrients (vitamins A, C, B12 and B6; folate; thiamine; riboflavin; zinc; copper; iron) were assayed in 73 patients with various forms of inherited epidermolysis bullosa (EB). Whereas the mean level for each nutrient was within its normal range, deficient levels were noted in individual EB subsets for selected nutrients. Notable abnormalities included low levels of plasma iron and zinc (in junctional EB and recessive dystrophic EB), vitamin C (primarily in EB simplex), vitamin A (in junctional and recessive dystrophic EB), vitamin B12 (primarily in EB simplex), and vitamin B6 (especially in recessive dystrophic EB). With the exception of low plasma iron and zinc levels in junctional and recessive dystrophic EB, however, only a minority of patients in any of the EB subsets had low levels of most of the other nutrients, and an apparent correlation with malabsorption was possible with only selected nutrients. PMID- 2923445 TI - Characteristic cutaneous lesions in patients with brucellosis. AB - Among 436 cases of brucellosis included in a 12-year prospective protocol, we identified 27 patients (6%) with cutaneous lesions (13 men and 14 women; mean age, 35.1 +/- 16.5 years). Twenty-one patients had positive blood cultures for Brucella melitensis. A disseminated violet-erythematous, papulonodular eruption (20 cases) and erythema nodosum-like lesions (three cases) were the most frequent eruptions observed, appearing during the initial episode of the disease or in relapse. Histologic findings were a dermal inflammatory infiltrate of lymphocytes and histiocytes in a perivascular and periadnexal arrangement, with a focally granulomatous appearance, and occasional extension to subcutaneous fat. Skin cultures were positive for B melitensis in two of four cases. Our results suggest that there are characteristic clinical and histologic cutaneous findings in patients with brucellosis and that hematogenous spread of the microorganism can be the most important pathogenic mechanism of these lesions. PMID- 2923446 TI - Subgaleal lipomas. AB - The subgaleal lipoma is a heterotopic tumor of adipose tissue appearing between the galea and periosteum of the frontal bone. In this tight, closed plane, the lipoma appears as a firm, fixed, immobile mass, unlike the usual lipoma. Clinical recognition of the subgaleal location is important before biopsy so that the incision is deep enough to find the tumor. PMID- 2923447 TI - Palisaded encapsulated neuromas. A clinicopathologic study. AB - Reed et al described the clinical and light-microscopic findings of palisaded encapsulated neuromas in 1972, but few cases have been reported since. We have studied 81 consecutive tumors. Clinically, these were solitary, asymptomatic, 2- to 6-mm, flesh-colored papules, usually located on the face of middle-aged patients. The correct diagnosis was rarely made; the lesion was most often mistaken for a basal cell epithelioma, melanocytic nevus, or other benign tumor. Light microscopy revealed single or multiple encapsulated dermal lobules composed of interlacing Schwann cells. Variable numbers of fine axons and myelin sheath remnants were present. Palisading of nuclei was not a prominent feature. Electron microscopy demonstrated substantial numbers of class C fibers (mostly nonmyelinated) only partially enveloped by Schwann cell cytoplasm. Pathologically, palisaded encapsulated neuromas are distinctive true neuromas resembling those seen in the multiple mucosal neuroma syndrome. Electron microscopic findings are similar to those seen in peripheral nerve regeneration, suggesting that palisaded encapsulated neuromas may be traumatic in origin, and could represent regeneration following local minor injury to the skin. PMID- 2923448 TI - Treatment of malignant carcinoid syndrome with a long-acting somatostatin analogue. AB - A patient with malignant carcinoid syndrome was treated with a long-acting somatostatin analogue. The cutaneous and systemic improvement our patient had while receiving this therapy is described. PMID- 2923449 TI - Eruptive dysplastic nevi associated with human immunodeficiency virus infection. AB - The cutaneous manifestations of the acquired immunodeficiency syndrome include infections and neoplasms resulting from the immunodeficient state. Seven patients presenting with the symptom of new eruptive nevi with dysplastic histologic findings are described. These patients noted multiple new moles, which occurred in crops and in individuals without the dysplastic nevus syndrome (familial melanomas). This symptom occurred as the patients became symptomatic from their human immunodeficiency virus infection, developing acquired immunodeficiency syndrome or its related complex. Further confirmation and study of this phenomenon could lead to a better understanding of the pathogenesis of melanocytic dysplasia and its relationship to the immune system. PMID- 2923450 TI - An unusual photoactivated skin eruption. Quinidine-induced livedo reticularis. PMID- 2923451 TI - Blue-gray discoloration of the face. Amiodarone-induced cutaneous hyperpigmentation. PMID- 2923452 TI - Solitary nodule of the scrotum. Leiomyoma. PMID- 2923453 TI - Multiple cutaneous plexiform schwannomas with tumors of the central nervous system. PMID- 2923454 TI - Kaposi's sarcoma in a 6-day-old infant with human immunodeficiency virus. PMID- 2923455 TI - Topical phototoxicity from oral methoxsalen capsules. PMID- 2923456 TI - Drug-induced photosensitivity reaction. PMID- 2923457 TI - Cutis verticis gyrata as a marker of internal malignancy. PMID- 2923458 TI - School holidays and admissions with asthma. AB - The admission rate for asthma at a children's hospital was studied over an 11 year period. Admissions varied unpredictably over periods of a few days, but there was a repeated yearly pattern of peaks and troughs with an interval of several weeks. The short term variation could be attributed to chance effects alone, excluding any important role for short term influences--for example, weather changes--in precipitating asthma admissions. There was a definite association between the longer term variation and school holidays. The admission rate fell during holidays and there were two or more peaks during terms. The pattern is consistent with a largely viral aetiology for asthmatic attacks throughout the year. We postulate that school holidays disrupt the spread of viral infections in a community, with synchronisation of subsequent attacks. Travel during holidays may facilitate acquisition of new viral strains by the community. PMID- 2923459 TI - Lung function eight years after neonatal ventilation. AB - Forty children who had had artificial ventilation during the neonatal period were studied at the age of 8-10 years with spirometry, the nitrogen washout test, bicycle exercise test, pulse oximetry, electrocardiogram, vectorcardiogram, and chest radiography. The median gestational age at birth was 29 weeks, and the median birth weight was 1310 g. Hyaline membrane disease was the indication for neonatal ventilation in 25 children. Bronchopulmonary dysplasia was diagnosed from radiographs in 11 infants (27%). Airway obstruction was observed in 10 of 11 children who had had bronchopulmonary dysplasia and in nine of 29 children who had not. After inhalation of terbutaline, the forced expiratory volume in one second (FEV1) was significantly increased. General hyperinflation was found in 16 of 17 children with abnormal chest radiographs (eight who had had bronchopulmonary dysplasia and nine who had not). Functional residual capacity was significantly higher in children with abnormal radiographs. Each child had a normal maximum working capacity and a normal electrocardiogram, and all but two had normal vectorcardiograms. Oxygen saturation at maximum work load decreased significantly in both groups of children. The risk of future respiratory problems calls for further follow up of lung function and chest radiography. PMID- 2923460 TI - Staff stress and job satisfaction at a children's hospice. AB - A study of staff stress and job satisfaction was undertaken in a children's hospice. In addition factors were investigated which might be stressful or which helped staff to manage in difficult circumstances. Three quarters were under comparatively little stress and in general showed very few psychological symptoms but a distinct subgroup were under a great deal of stress. A number of factors, notably recent personal bereavement and unresolved grief about a death that had occurred before they came to work at the hospice, distinguished this small group. Job satisfaction was generally high. The main sources of stress were: the sense of impotence staff felt when they were unable to relieve perceived needs or distress; dealing with negative responses in families, and conflicts within the staff group. The most important mitigating factors were: the informal support that staff provided for each other in this small cohesive working unit, the homelike atmosphere of the hospice, and the diversity of professional and personal skills among the staff group. The implications of these findings for reducing stress among staff dealing with dying people are discussed; this includes not only staff on paediatric wards, intensive care and neonatal units, but also community paediatric nurses. PMID- 2923461 TI - Totally implantable venous access systems in paediatric practice. AB - Forty seven totally implantable venous access systems have been inserted in 45 patients for the management of malignant disease (n = 29), haematological disorders (n = 5), and cystic fibrosis (n = 11). We report our experience with them and discuss the problems we have encountered during the past three years. PMID- 2923462 TI - Symptoms and signs of progressive hydrocephalus. AB - The clinical features of 107 cases of children with hydrocephalus and measured raised intraventricular pressure were analysed retrospectively. Fifty one children had recently been diagnosed as having hydrocephalus, and the remainder had had shunts injected to direct the cerebrospinal fluid. The most common symptoms in the group were vomiting, behavioural changes, drowsiness, and headaches. The most common clinical signs were inappropriately increasing occipitofrontal head circumferences, tense anterior fontanelles, splayed sutures, and distension of the scalp veins. Half the infantile cases of hydrocephalus were without symptoms, and a quarter of the cases with cerebrospinal fluid shunts and measured raised intraventricular pressure were without signs. There were no fewer than 33 different clinical signs including several unusual ones, such as macular rash and sweating. We believe that the presentation of hydrocephalus with raised intraventricular pressure is sufficiently variable, unusual, or even absent to justify the direct measurement of intracranial pressure. PMID- 2923463 TI - Renal tubular proteinuria and microalbuminuria in diabetic patients. AB - The urinary extraction of albumin, retinol binding protein, and N-acetyl-beta-D glucosaminidase were studied in 60 children with insulin dependent diabetes mellitus and in 45 normal children to find out whether the renal tubules played a part in causing the early increase in urinary excretion of albumin that occurs in diabetes mellitus. Two overnight urine samples were collected and the protein excretion measured and expressed as the geometric mean of the protein to creatinine ratio (urinary albumin:creatinine ratio, urinary retinol binding protein:creatinine ratio, and urinary N-acetyl-beta-D-glucosaminidase:creatinine ratio, respectively). The excretion of all three proteins was significantly higher in the diabetic children with 15 (25%) of urinary albumin:creatinine ratio, 16 (27%) of urinary retinol binding protein:creatinine ratio, and 43 (72%) of urinary N-acetyl-beta-D-glucosaminidase:creatinine ratio values being above the normal range. Significant correlations were observed between urinary albumin:creatinine ratio and urinary retinol binding protein:creatinine ratio, urinary albumin:creatinine ratio and urinary N-acetyl-beta-D glucosaminidase:creatinine ratio, and urinary retinol binding protein:creatinine ratio and urinary N-acetyl-beta-D-glucosaminidase:creatinine ratio. There were also significant correlations between glycated haemoglobin 1c (HbA1c) and these proteins, especially N-acetyl-beta-D-glucosaminidase. No correlations were observed with the fractional excretion of sodium, flow rate of urine, glomerular filtration rate, or blood pressure. These data show that tubular abnormalities are present early in the course of insulin dependent diabetes mellitus and suggest that the early increase in urinary excretion of albumin may be at least partly tubular in origin, and that glycaemic control may influence this aspect of proximal tubular function. PMID- 2923464 TI - Pyloric stenosis: congenital or acquired? AB - Pyloric muscle dimensions were measured in 1400 consecutive newborn infants. Nine of these subsequently developed pyloric stenosis. Their pyloric measurements at birth were all within the normal range. Congenital preformed muscular hypertrophy does not appear to be present in babies who later develop pyloric stenosis. PMID- 2923465 TI - Dysphagia due to oesophageal web. AB - An 8 year old boy developed a recurrent sensation of food sticking in his throat during meal times. Barium swallow examination showed an anterior oesophageal web at the level of C5. Symptoms disappeared after pharyngoscopy and dilatation of the web. PMID- 2923466 TI - Spontaneous regression of congenital epulis of the newborn. AB - An infant with congenital gingival epulis which spontaneously regressed over the first year of life is reported. A policy of conservative management should be adopted in this condition unless there are feeding problems in the newborn period or reasons to doubt the diagnosis. PMID- 2923467 TI - Shared care in paediatrics. PMID- 2923468 TI - Families with congenital heart disease. AB - Families with congenital heart deformities appear to have more difficulties and stress than those with other deformities. Some problems are intrinsic to the deformity but others are largely related to communication difficulties between the groups doing home support and those in supraregional centres. PMID- 2923469 TI - Joint work in paediatrics: a child psychiatry perspective. PMID- 2923470 TI - Brittle or battered? PMID- 2923471 TI - Good tolerance of pyrazinamide in children with pulmonary tuberculosis. PMID- 2923472 TI - Accidental poisoning. PMID- 2923473 TI - Cerebral arterial air embolism in experimental neonatal pneumothorax. PMID- 2923474 TI - Recurrent cot death and suffocation. PMID- 2923475 TI - Measuring severity of injuries to children from home accidents. PMID- 2923476 TI - Children in specialist hospital departments. PMID- 2923477 TI - Insecticides in pediculosis capitis. PMID- 2923478 TI - Reversal of desferrioxamine induced auditory neurotoxicity during treatment with Ca-DTPA. AB - Auditory neurotoxicity occurred in 13 (26%) of 50 evaluable patients receiving long term desferrioxamine chelation. In five of these patients, all of whom were receiving high doses of desferrioxamine, the toxicity caused deafness. These five patients were treated with subcutaneous calcium diethylene triamine pentacetic acid (Ca-DTPA) with zinc supplements instead of desferrioxamine, and their hearing improved during periods of seven to 19 months. Their serum ion concentrations remained unchanged. We suggest that all patients receiving long term desferrioxamine should have audiometric assessments at 6-12 monthly intervals. Ca-DTPA with oral zinc supplements should be considered as alternative to desferrioxamine as an iron chelating treatment in patients with auditory neurotoxicity. PMID- 2923479 TI - Production of interferon in respiratory syncytial virus bronchiolitis. AB - Production of interferon alfa in vitro was significantly reduced during acute respiratory syncytial virus bronchiolitis but subsequently returned to normal. Nasopharyngeal and endotracheal interferon alfa were detected intermittently and in low concentrations. The degree of impairment of in vitro production and poor in vivo production of interferon alfa suggest the need for a therapeutic trial of nebulised or systemic interferon in acute bronchiolitis. PMID- 2923480 TI - Growth and other factors affecting peak expiratory flow rate. AB - By means of a simple questionnaire and measurements of height, weight, and peak expiratory flow rates 3061 children from city and rural populations were studied. Children with asthma or other respiratory diseases had lower peak expiratory flow rates, and younger children living in rural areas had higher rates. In 2828 healthy children the peak expiratory flow rate increased with age, height, and weight. There was an increase in the slope of this line for both age and height- at 12 years and 145 cm in girls, and at 14 years and 155 cm in boys. This continued for two to three years and 15 cm, respectively, before it declined. Previous surveys have obscured this change associated with height by reporting small numbers and using linear regression analysis. This type of analysis can underestimate the mean peak expiratory flow rate of small children by half to one standard deviation. A centile graph against age is recommended to describe normal values and their differences. PMID- 2923481 TI - Management of posthaemorrhagic hydrocephalus with a subcutaneous ventricular catheter reservoir in premature infants. AB - A subcutaneous ventricular catheter reservoir was inserted between the 16th and 28th (median 23rd) day of life in 13 premature infants (median birth weight 1220 g, range 780-2110) for the treatment of posthaemorrhagic hydrocephalus. Aspiration of cerebrospinal fluid (median 6 ml, range 1-15) one to four (median two) times a day for 6 to 90 (median 40) days controlled the hydrocephalus as judged by clinical and ultrasonographic criteria. There were no serious complications, except skin breakdown in one patient. Intracranial pressure measured in five patients through the reservoir showed the efficacy of the treatment, as well as the unreliability of clinical and ultrasonographic criteria in determining the amount of cerebrospinal fluid that should be aspirated daily. PMID- 2923482 TI - Providing warmth for preterm babies by a heated, water filled mattress. AB - Seventeen healthy preterm babies had extra warmth provided in their cots by thermocontrolled, heated, water filled mattresses. As controls 17 babies of the same weight were nursed in air heated incubators. Both groups were studied for three weeks. No differences were found in minimal oxygen consumption (measured by indirect calorimetry), rectal and mean skin temperatures, or in daily weight gain. The babies were kept just as warm on the heated, water filled mattresses as in air heated incubators but the mattresses had the advantage of giving the mothers easy access to their babies. PMID- 2923483 TI - Routine endotracheal cultures for the prediction of sepsis in ventilated babies. AB - Serial cultures of endotracheal tube aspirates were carried out in 94 neonates who were intubated and had been ventilated for longer than one week. A similar change in bacterial colonisation with duration of ventilation was seen in infants who subsequently developed sepsis and those who did not. In both groups, 177 aspirates (more than 90%) obtained during the first week of ventilation were sterile. Thereafter, colonisation with mixed Gram positive flora emerged followed by growth of Gram negative bacilli. For the infants who developed sepsis, the correlation between pathogens isolated from blood during the episodes of sepsis and those from previous endotracheal tube isolates was poor; in only five of the 26 cases of sepsis (19%) was the same single strain of organism isolated from culture of the blood and of the endotracheal tube aspirate. Other markers of infection such as endotracheal tube aspirate white blood cell counts and changes in bacterial flora were not useful in predicting systemic infection. Routine surveillance cultures of endotracheal tube aspirates in ventilated infants are not helpful in predicting the pathogens that are isolated from the blood during episodes of sepsis. PMID- 2923484 TI - Prediction and diagnosis of sickling disorders in neonates. AB - A pilot scheme for the prediction and detection of sickle cell disease in neonates was set up and the results from its first three years of operation analysed. A total of 153 women booking at the antenatal clinic were found to have haemoglobin S. The protocol required that all partners of the women so identified be screened for abnormal haemoglobins and beta thalassaemia trait, and that the babies of these women should have cord blood electrophoresis performed. In fact this was only achieved in 75 partners (49%) and 91 of 145 infants (63%). Of 10 babies born with sickle cell disease during the study period, nine had mothers known to have haemoglobin S or C, but only four of these mothers' partners had been tested before delivery of the child. This pilot study highlights the problems in establishing effective antenatal screening programmes, especially in ethnic minority groups. The results show that detailed staff training, careful organisation of administrative arrangements, and education of 'at risk' groups should all be undertaken before the launching of major screening initiatives. PMID- 2923485 TI - Suckling stimulation test for neonatal tremor. AB - The response of neonatal tremor to a suckling stimulation test was investigated in 102 healthy neonates born at full term. In 84 the tremor resolved immediately; none had hypocalcaemia and only one had mild hypoglycemia. Eighteen in whom the tremor continued had either hypocalcaemia (n = 13) or hypoglycaemia (n = 5). PMID- 2923486 TI - Simple test to distinguish between surgical and non-surgical pneumoperitoneum in ventilated neonates. AB - A simple and accurate method is described for rapid differentiation of surgical and nonsurgical pneumoperitoneum by measuring the partial pressure of oxygen in intraperitoneal air with a blood gas analyser. Results in five ventilated neonates in whom this distinction was not possible by clinical or radiographic means are presented. PMID- 2923487 TI - Neonatal bilateral diaphragmatic paralysis caused by brain stem haemorrhage. AB - We describe a neonate with severe bilateral diaphragmatic paralysis caused by haemorrhage in the lower brain stem. To our knowledge this association has not been previously reported in the English medical literature. PMID- 2923488 TI - Effect of infusion rate of indomethacin on cerebrovascular responses in preterm neonates. AB - Cerebrovascular responses were studied in preterm infants by Doppler ultrasound and cerebral electrical impedance for one hour after intravenous indomethacin infusion for patent ductus arteriosus. Indomethacin in a dose of 0.2 mg/kg body weight was infused over five minutes in one group of infants (20 doses) and over 20 minutes in a second group of infants (16 doses). There were no significant differences between the two groups in birth weight (mean = 1068 g, range 569 1950), gestational age (mean 28.4 weeks, range 25-31), or postnatal age (mean 18.1 days, range 6-42). There was a significant reduction in both the Doppler mean flow velocity in the anterior cerebral artery (mean (SE) -20 (4.2)%) and peak amplitude of cerebral electrical impedance (-26 (3.9)%) within two minutes of starting the indomethacin infusion over five minutes. There was no significant change after the infusion over 20 minutes. There were no significant changes in blood pressure or carbon dioxide tensions after infusion at either rate. The results suggest that infusion of indomethacin over five minutes caused a potentially deleterious reduction in cerebral blood flow. No such reduction occurred when it was infused over 20 minutes. PMID- 2923489 TI - Experimental acidification of Little Rock Lake (Wisconsin): fish research approach and early responses. AB - One goal of research at Little Rock Lake, Wisconsin, is to enhance understanding of lake acidification effects on warm- and cool-water fishery resources. The Little Rock Lake fish assemblage is characteristic of many acid sensitive waters in North America and is dominated by yellow perch (Percidae) and sunfishes (Centrarchidae). Analyses of reproduction, early survival and growth rates in the field were designed around the differing reproductive modes of these taxa. Complementary laboratory research on early life stages was conducted to assist in isolating direct effect mechanisms and to determine the reliability of laboratory results in predicting field response. Preliminary findings suggest that lake acidification to pH 5.6 has not influenced reproductive activity of the four most abundant fish species. However, the field results suggest that year-class failure of rock bass (Ambloplites rupestris) may be occurring due to reduced survival of early life stages. Reduced growth and food conversion efficiency of Age 0 largemouth bass (Micropterus salmoides) is also suggested. The laboratory bioassays indicate rock bass is the most acid-sensitive Little Rock Lake species tested. However, rock bass fry survival was not significantly affected until pH was reduced from 5.6 to 5.0. PMID- 2923490 TI - Characteristics of three acidic lakes in Kejimkujik National Park, Nova Scotia, Canada. AB - This report summarizes a study of the chemical and biological characteristics of three oligotrophic lakes located in a region that receives a moderately acidic precipitation (mean annual pH 4.5-4.6), and a sulfate deposition of about 20 kg/ha/yr. The two brownwater lakes are relatively acidic (pH 4.5 and 4.8), and much of their acidity is attributable to organic anions. The brownwater lakes also have a large concentration of aluminum and iron, but these are bound to dissolved organic matter and are relatively non-toxic to biota. Average phytoplankton production was largest in the clearwater lake. This was due to its relatively deep euphotic zone, since the average unit-volume productivity did not differ much among the lakes. In fact, productivity at light optimum was largest in the most acidic brownwater lake, probably because of its larger phosphorus concentration. The clearwater lake had extensive macrophyte vegetation, which covered its bottom to a depth of 6.5 m. In the brownwater lakes, macrophytes were confined to shallow nearshore water because of the limited water transparency. Zooplankton density and biomass were largest in the most acidic brownwater lake, probably because of allochthonous organic particulates and little fish predation. Benthic invertebrates were abundant in all three lakes, and were dominated by insects, especially Chironomids. Lakes in the study area appear to be sustaining fish populations at more acidic pHs than elsewhere. This may be due to the large concentration of dissolved organic matter in many lakes, which complexes and partially detoxifies metals such as aluminum. PMID- 2923491 TI - Oocyte atresia and reproductive success in fathead minnows (Pimephales promelas) exposed to acidified hardwater environments. AB - The ovarian histology of fathead minnows (Pimephales promelas) chronically exposed to three levels of environmental pH was examined for evidence of reproductive impairment. Exposures occurred in three experimental running-water channels receiving Mississippi River water. One of these channels was not acidified and two were dosed with H2SO4. The pH was approximately 8 in untreated river water and 6 and 5 in the two channels receiving H2SO4. Fish for ovarian examination were taken from these channels at four stages of the reproductive season: initiation of spawning (June 19), mid-spawning (July 12), end of spawning (August 14-15), and approximately 1 mo. post-spawning (September 19). The fish exhibited ovarian histological changes and depression of reproductive success which were directly associated with the level of environmental stress experienced. The association between these three factors was most consistent and pronounced if the fish were sampled near the end of the spawning season. When sampled at this time, reproductive impairment in a population was found when the ratio of the volume of atretic (resorbing) oocytes present in the ovary to the total ovarian volume exceeded 20% in all fish sampled. This was the case in the pH 5 channel fish sampled in August. At this same time, not all of the fish in the pH 6 channel exhibited such an accumulation of atretic oocytes, and egg deposition in that population was not reduced. None of the fish from the pH 8 channel were so affected nor was their reproduction. PMID- 2923492 TI - Short-term experimental acidification of a Welsh stream: toxicity of different forms of aluminium at low pH to fish and invertebrates. AB - A 24-hr dosing experiment was carried out in a soft-water stream in upland Wales during which four separate zones were created by the simultaneous addition of sulphuric acid, aluminium sulphate, and citric acid. An upstream control zone (A), an acid zone pH 4.9 (B), an aluminium and acid (total filterable aluminium 0.27 mg/L, pH 4.9) zone (C) and a downstream zone (D) of aluminium complexed with citrate at low pH (total filterable aluminium 0.23 mg/L, pH 4.9). Test species exposed in all zones were the invertebrates Gammarus pulex (L.), Baetis rhodani (Pict.), Ephemerella ignita (Poda) and the fish Salmo salar L., Salmo trutta L. and Cottus gobio L. Response criteria measured were mortality, feeding, effects of pretreatment, brief-exposure, and the ability of animals to recover. Minimal effects were observed in the control and acid zones whilst large mortalities and reduced feeding were recorded in the acid and aluminium zone. These effects were significantly reduced in the acid, aluminium and citrate zone due to complexation of aluminium with citrate. PMID- 2923493 TI - Lethality of trace metal mixtures to American flagfish in neutralized acid water. AB - Acute lethality of H+ alone to fry of American flagfish (Jordanella floridae) produced a 96 hr LC50 at pH 4.82 in very soft water (5.5 mg/L as CaCO3). At pH 5.3, the combined lethality of Al, Zn, Cu, and H+ produced an LC50 corresponding to 17, 2.8, and 1.4 micrograms/L, of Al, Zn, and Cu, respectively, acting as a mixture. Raising exposure pH from 5.3 to 6.9 in the same soft water reduced apparent Al/Zn/Cu lethality by a factor of 2.6. Decreased mixture lethality was attributed more to reduced H+ lethality at higher pH than to the modifying effects of pH on metal lethality. Neutralization acidic, metals-enriched, soft water with dolomite raised pH from 5.84 to 6.84, total hardness from 5.1 to 17.2 mg/L (as CaCO3) and reduced metal lethality by a factor of 2.4. Reduced lethality was attributed equally to elevated pH and to elevated hardness and alkalinity. Neutralization of culturally acidified waters will reduce the acute lethality of H+ and metals to biota. PMID- 2923494 TI - Metal contents in liver tissues of non-fledged goldeneye, Bucephala clangula, ducklings: a comparison between samples from acidic, circumneutral, and limed lakes in south Sweden. AB - The risk of increased exposure to metals for a vertebrate predator foraging on aquatic insects in acidified lakes was investigated through analyses of the content of Al, As, Ca, Cd, Cu, Fe, Hg, Mn, Pb, Ru, Se, and Zn in the liver tissue of 42 non-fledged Goldeneye, Bucephala clangula, ducklings from acidic, circumneutral, and limed lakes in South Sweden. No indications of significantly different concentrations in samples from acidic lakes in comparison with circumneutral lakes were detected for any metal, but among individual birds from acidic lakes there were high contents of Hg. Liming probably affects the exposure to some metals; lower contents of Hg were recorded from limed lakes in comparison with acidic lakes, while the reverse trend was recorded for Cd and Mn. PMID- 2923495 TI - Regional anomalies in chronic obstructive pulmonary disease; comparison with acid air pollution particulate characteristics. AB - Mortality rates due to chronic obstructive pulmonary disease (COPD) for males and females in standard metropolitan statistical areas are highest in two broad regions of the U.S. One is the southeast, with age-adjusted rates high in Georgia and north Florida but decreasing toward south Florida; the other is the western plains, with rates high in Colorado and north Texas but decreasing toward south Texas. Rates are generally low in the northeast, upper midwest, and far west, as well as in the largest cities of these regions. These geographic patterns suggest that atmospheric environmental conditions may contribute to the risk of COPD. Based on measured aerosol characteristics and atmospheric chemical reasoning, it is argued that ambient air in the high COPD regions may be especially irritating to the respiratory tract because of fine particles that contain the reaction products of acid air pollutants. In the southeast, sulfuric acid aerosol concentrations are high, apparently because of a sunny warm humid climate that favors rapid oxidation of sulfur dioxide as well as the region's proximity to large primary air pollution sources further north. Particulate sulfur is also associated with soil mineral constituents. In the western plains, concentrations of alkaline dust are high because of soil erosion during windy dry conditions. Acid air pollutants can be scavenged to mineral particle surfaces and form chemical reaction products that may include solubilized mineral aluminum. These may be inhaled and deposited in the respiratory tract so as to contribute to COPD mortality risk. PMID- 2923496 TI - Acid rain: what we know, what we did, what we will do. AB - This paper reviews the involvement of the Canadian province of Ontario in the acid rain issue. Ontario is a major producer of acid gas emissions and suffers significant environmental consequences because of acid rain. The province's substantial contribution to the scientific understanding of acid rain is summarized with emphasis on the extent and origins of the deposition it receives, the impact on the aquatic environment, and the impact on the terrestrial environment. This paper discusses the history of the government's success at reducing acid gas emissions through the 1970's when legislators set out to enhance local or "ambient" air quality, the first legislation to require SO2 reductions from companies already in compliance with ambient air quality legislation, and the current Countdown Acid Rain program which reduces SO2 emission limits by 67%. The process used to establish the tough new limits while reasonably anticipating the development of SO2 control technologies is detailed along with the specific requirements of the major emitters controlled by the regulations. Projections confirm that while the Countdown reductions will bring about significant reductions in deposition, adequate environmental protection in Canada cannot be achieved without some comparable U.S. acid gas abatement effort. PMID- 2923497 TI - Development of a sleep-awake instrument for use in a chronic renal population. AB - A pilot study with nine subjects was completed to test instruments and refine methodology for a study of sleep-awake behaviors in end stage renal disease (ESRD) hemodialysis clients pre- and post-ESRD diagnosis with concomitant hemodialysis treatment. The development of the instrument is described. Several sources contributed to content validity. Stability was tested through test-retest reliability. PMID- 2923498 TI - Creating a therapeutic environment in a pediatric renal unit. AB - Creating and maintaining a therapeutic patient environment has been the responsibility of nurses since the days of Florence Nightingale. Achieving this environment for children with renal disease and their families can, however, be a complex task. This article addresses a number of factors that must be considered in planning a new pediatric unit or renovating an established one. Useful strategies leading to a therapeutic environment in a pediatric nephrology unit are described as well. PMID- 2923499 TI - Peritoneal dialysis transfer set change procedures study. AB - The purpose of this in vitro study was to evaluate the effectiveness of continuous ambulatory peritoneal dialysis (CAPD) procedures. Four procedures to disinfect the catheter adapter/transfer set connection were compared in vitro using a mock sterile CAPD system. PMID- 2923500 TI - Continued bone disease and symptoms post-parathyroidectomy. PMID- 2923501 TI - Strike--you've got to be kidding! PMID- 2923502 TI - Does rheumatoid factor protect lupus patients from the development of nephritis? AB - It has been suggested again recently that the presence of rheumatoid factor (RF) in the serum of patients with systemic lupus erythematosus (SLE) protects them from the development of nephritis. In this study the RF is measured by standard latex test and by radioimmunoassay to detect IgM, IgA, and IgG isotypes, in patients with SLE with (26 patients) and without (25 patients) renal involvement, and in a control group of 21 patients with idiopathic renal disease. In addition, patients with SLE and nephritis were tested during active and inactive phases of their disease. No significant protective effect was observed from the presence of RF. PMID- 2923503 TI - Measurement of sulphated glycosaminoglycans and proteoglycan fragments in arthritic synovial fluid. AB - Immunoreactive proteoglycans (iPGs) and sulphated glycosaminoglycans (GAGs) were assayed in synovial fluid obtained from 22 patients with osteoarthritis (OA), 21 with rheumatoid arthritis (RA), 13 with gout, and five with Reiter's syndrome. A strong positive linear correlation was observed between concentrations of sulphated GAGs and iPGs in RA (r = 0.95) and gout (r = 0.94). A linear correlation was also observed in OA (r = 0.65). Patients with gout and Reiter's syndrome had significantly higher concentrations of sulphated GAGs and iPGs than patients with OA or RA. Patients with gout also had significantly higher total quantities of sulphated GAGs and iPGs in the knee joint cavity than patients with OA or RA. In all four diseases similar profiles were observed when comparisons were made between the total quantities and concentrations of sulphated GAGs and iPGs in synovial fluid. These results indicate that the observed differences in concentrations are not simply a function of dilution. The concentrations of sulphated GAGs and iPGs did not correlate closely with the type or number of inflammatory cells in the synovial fluid. Considerable variation was noted in the sulphated GAG/iPG ratios, suggesting that different mechanisms may be contributing to the release of proteoglycans in the diseases studied. PMID- 2923504 TI - Erosion number and area progression in the wrists and hands of rheumatoid patients: a quantitative microfocal radiographic study. AB - Microfocal radiography has been used to evaluate the relation between erosion number and erosion area in the hands and wrists of 51 patients with early to moderately advanced rheumatoid arthritis. The hands of these patients showed different patterns of erosion progression, in terms of the relation between changes in number and area, and included those showing a decrease in one or both of the erosion parameters. The mean number of erosions in the group increased between the first and second visits. By the third visit (a mean of 48 months from the onset of symptoms) the mean number of erosions in the wrist and hand of the group had approached a constant value of 75 erosions. Over the same period the mean erosion area of the group continued to increase. Measurement of changes in erosion area is a more sensitive indicator of erosion progression than erosion number, both within the group and in individual patients. PMID- 2923505 TI - Osteoarthritis of the hip and Heberden's nodes. AB - One hundred consecutive patients with proved osteoarthritis were assessed for the presence of terminal interphalangeal joint disease. There was a significant association found between the presence of Heberden's nodes and primary (axillary) arthritis. Secondary osteoarthritis was relatively free of nodal involvement. It is suggested that Heberden's nodes are a helpful clinical marker in differentiating between the two major groups of osteoarthritis. PMID- 2923506 TI - Rheumatoid arthritis in blacks in South Africa. AB - The spectrum of rheumatoid arthritis (RA) was studied in a group of 52 blacks who attended a rheumatology unit in Cape Town, South Africa. The mean age of the patients was 44.6 years, and the female to male ratio was 3.7:1. Significant radiographic changes were frequently noted, and the mean Larsen scores were 34.9 for the hands, 19.6 for the feet, and 6.6 for the wrists. About two thirds of the patients had received an immunomodulatory drug and 20 (38%) had had one or more surgical procedures for their RA. Anaemia was the commonest extra-articular manifestation, and although the other extra-articular features were uncommon, a variety of features had been detected during the course of the disease. Earlier studies on blacks in Africa suggested that RA was a mild disease; our findings, however, are in agreement with the more recent surveys, which suggest that severe disease is not uncommon. PMID- 2923507 TI - Factors predicting a poor life prognosis in rheumatoid arthritis: an eight year prospective study. AB - This prospective study evaluates the usefulness of clinical features and measurements of circulating immune complexes and autoantibodies for identification of patients with rheumatoid arthritis with a poor life prognosis. One hundred and seven hospital clinic patients, 64 with extra-articular manifestations, were followed up for a mean period of eight years, during which 50 deaths occurred. Comparison with an age and sex matched control population showed an increased incidence of deaths from myocardial infarction, pneumonia, and complications of rheumatoid arthritis. Patients with cutaneous ulcers, vasculitic rash, neuropathy, and scleritis had a higher mortality than patients whose disease was confined to the joints. Positive serological tests for precipitating antibodies to soluble cellular antigens and cryoglobulinaemia also predicted a poor prognosis. Eleven out of 12 patients (92%) with antibodies to soluble cellular antigens died compared with 21 out of 64 patients (33%) without antibodies. The presence of cryoglobulinaemia was associated with almost a twofold higher mortality. The laboratory measurements may reflect immunopathogenic mechanisms which lead to the occurrence of extra-articular disease features and reduce life expectancy. PMID- 2923508 TI - Antibodies to HTLV-I in sera from patients with connective tissue diseases. PMID- 2923509 TI - Anticardiolipin antibodies in systemic lupus erythematous. PMID- 2923510 TI - Lyme arthritis in Spain. PMID- 2923511 TI - Cyclosporin for dermatomyositis. PMID- 2923512 TI - Endoscopic placement of pancreatic stents and drains in the management of pancreatitis. AB - Although widely used in the biliary tree, little data is available on endoscopic placement of stents or drains within the pancreas. This report describes 17 patients, nine with acute relapsing pancreatitis and eight with chronic pancreatitis, who had drain or stent placement for hypertensive pancreatic duct (PD) sphincter, dominant ductal stenosis, duct disruption, or pseudocyst. Two patients have subsequently undergone surgery, and six other patients continue long-term stent placement with marked reduction of chronic pain or attacks of recurrent pancreatitis. All six pseudocysts resolved, although one recurred and required surgery. It is concluded that pancreatic drains or stents may obviate the need for surgery, temporize before definitive therapy, or direct a subsequent surgical procedure. PMID- 2923513 TI - Selective ERCP and preoperative stone removal in bile duct surgery. AB - This project was undertaken to evaluate in a prospective fashion the effects of selective preoperative endoscopic-retrograde cholangiography and stone extraction (ERCP-ST EXTR) on the results of biliary tract surgery. Over a 6-year period, 728 patients with primary or secondary biliary tract disease were admitted to the First Surgical Department, landeskrankenanstalten, Salzburg, Austria. If, based on preoperative screening, the possibility of common bile duct stones (CBDS) existed, the patients were subjected to ERCP-ST EXTR. Two to 4 days later, these patients underwent a simple cholecystectomy with intraoperative cholangiogram and functional manometry. Evaluation criteria for this study were morbidity, mortality, and retained stone (RST) rates. The overall complication rate for the entire series was 6%. In patients who underwent operative common duct stone removal (n = 78), the complication rate amounted to 21.8%. The rate was reduced to 2.1% by ERCP-ST EXTR. The RST rate was likewise reduced from 2.2% to 0.5% by ERCP-ST EXTR. Mortality in patients with CBDS fell from 3.8% to 1% through the use of this method. In those patients with secondary stones who were treated by ERCP-ST EXTR only, morbidity was 2%, the RST rate was 0%, and mortality was 0%. It is concluded that selective ERCP-ST EXTR, followed by simple cholecystectomy, is a suitable treatment protocol and that this approach may reduce complication and mortality rates. PMID- 2923514 TI - Duodenum-preserving resection of the head of the pancreas in severe chronic pancreatitis. Early and late results. AB - In 128 patients with severe chronic pancreatitis and inflammatory enlargement of the head of the pancreas, a duodenum-preserving resection of the pancreatic head was performed. Median post-operative hospitalization was 15.5 days, and the frequency of reoperation was 5.5%. One patient died during the early post operative phase, and hospital mortality amounted to 0.8%. After a median follow up period of 3.6 years (range of 7 months to 16 years), six of 127 patients died (late mortality of 4.7%). Seventy-seven per cent of the patients were completely free of abdominal pain, 67% returned to their former occupations. During the late follow-up period, the glucose metabolism was unchanged in 80.7% of the patients, in 13.7% it deteriorated, and in 5.5% it improved permanently; 80% of the patients experienced a marked increase in weight averaging 8.7 kg. Compared with the Whipple procedure, the duodenum-preserving resection of the head of the pancreas spares the patient with chronic pancreatitis a gastrectomy, duodenectomy, and resection of the extrahepatic biliary ducts. In terms of a subtotal resection, the limited operative intervention at the head of the pancreas and the preservation of the duodenum explain the low early and late postoperative morbidity and mortality. PMID- 2923515 TI - Prostaglandin-induced gastric mucosal protection against stress injury. Absence of a relationship to tissue glutathione levels. AB - The effects of 16,16 dimethyl prostaglandin E2 (dmPGE2) on the gastric mucosa of rats subjected to 1, 2, and 24 hours of water immersion stress were examined histologically. Results indicated a time-related increase in the total percentage length of glandular mucosa injured in normal saline (NS) pretreated rats that was significantly attenuated by subcutaneous dmPGE2 pretreatment (5 micrograms/kg) after 1 hour (46.0 +/- 12.9 vs. 16.8 +/- 2.3; p less than 0.005), 2 hours (45.4 +/- 1.0 vs. 13.8 +/- 2.2; p less than 0.001), and 24 hours (93.1 +/- 2.6 vs. 65.1 +/- 7.0; p less than 0.005) of water immersion stress. Moreover, dmPGE2 essentially prevented the occurrence of deep, glandular injury that, in NS controls, involved approximately 13% and 26% of the mucosal surface after 2 and 24 hours of immersion stress, respectively. Additionally, tissue levels of glutathione (mumole/g weight of wet tissue) were measured to determine its role under such conditions. After 1 hour of stress, there were no differences in glutathione levels between NS or dmPGE2 pretreated animals and fasted controls. After 2 and 24 hours of stress, there were likewise no differences in glutathione levels between NS and dmPGE2 pretreated groups, although levels in both groups were significantly decreased from fasted controls by approximately 30% at 2 hours and 37-47% after 24 hours. These histologic and biochemical data indicate that dmPGE2 attenuates both the extent and depth of glandular mucosal injury and does so in a manner unrelated to alterations in glutathione levels in gastric epithelium. PMID- 2923516 TI - Postoperative changes in serum creatinine. When do they occur and how much is important? AB - The objective of this study was to evaluate the use of the serum creatinine in following postoperative renal function. In this prospective study of 278 patients (mainly hypertensives and diabetics) undergoing noncardiac surgery, the serum creatinines were followed from the first through the sixth postoperative day. Creatinine clearances were evaluated before operation and on the fourth to fifth postoperative day. During the first six days after the operation, 23% (65 of 278 patients) had an increase of serum creatinine greater than or equal to 20%. Such increases were sustained for greater than or equal to 48 hours in 12% of the patients (32 of 278), and half of these patients had not returned to their initial level of renal function by the time of discharge. Patients who sustained such a deterioration were at risk for nonoliguric renal failure if they had a subsequent insult (i.e., hypotension, reoperation, angiography, aminoglycosides). Such increases occurred early in the postoperative period--on the first or second postoperative day. As judged by the creatinine clearances, postoperative increases of greater than or equal to 20% in the serum creatinine identified most patients whose clearance fell more than 50%, although the serum creatinine did not accurately reflect changes in creatinine clearance among those patients who had undergone an amputation. It is concluded that the serum creatinine is useful in monitoring postoperative renal function. Of those patients who had postoperative increases in serum creatinine sustained for greater than or equal to 48 hours, as many as one third had evidence of impairment in renal function at the time of discharge. PMID- 2923517 TI - Right and left ventricular performance during and after abdominal aortic aneurysm repair. AB - To evaluate the effect of aortic occlusion and limb reperfusion on global and regional function of the right and left ventricle during infrarenal abdominal aortic aneurysm repair, 23 patients underwent five intraoperative first-pass radionuclide angiocardiograms: 1) before the skin incision, 2) at aortic cross clamp, 3) 20 minutes after aortic occlusion, 4) at unclamping, and 5) after skin closure. A subset of twelve patients had simultaneous transesophageal echocardiography to evaluate left ventricular wall stress. Parameters measured included the electrocardiogram (ECG), heart rate, blood pressure, pulmonary artery pressure, the cardiac output, the left and right ventricular ejection fractions, left ventricular volumes, and left ventricular wall stress. Significant changes (p less than 0.01) were observed at aortic clamping in the left ventricular ejection fraction (from 0.56 to 0.48), end-diastolic volume (from 171 to 225 ml), end-systolic volume (from 85 to 127 ml), mean blood pressure (from 82 to 91 mmHg), and meridional end-systolic wall stress (from 53 to 67 10(3) dyne/cm2). Once the clamp was removed, significant variations were seen in the left ventricular ejection fraction (from 0.51 to 0.58), end-diastolic volume (from 205 to 187 ml), end-systolic volume (from 105 to 94 ml), mean blood pressure (from 84 to 69 mmHg), and meridional end-systolic wall stress (from 67 to 46 10(3) dyne/cm2). No differences were observed between the two aortic occlusion studies, and the baseline level of function was recovered in all parameters during the last study. These data quantify the changes in heart function that occur during abdominal aortic aneurysm operation and demonstrate that the majority of the adaptations that occurred were due to a variation in afterload. PMID- 2923518 TI - Photodynamic therapy with haematoporphyrin derivative on mice with solid Ehrlich carcinomas. AB - The tumor-toxic effect of the photosensitizer HpD/Halle activated by laser radiation was demonstrated. Solid Ehrlich carcinoma was used as model. Investigations into the tumor growth, the HpD-distribution after different kinds of drug administration by means of fluorescence measurements, the phototoxicity and the reduction of tumor masses after HpD application and laser irradiation were carried out. PMID- 2923519 TI - [Temperature, pH value, acid load and filtrability of normal human erythrocytes: in vitro studies--possible significance for hyperthermic hyperacidotic tumor therapy]. AB - Normal human red blood cells, taken from healthy young men were separated from the other blood cells with the aid of a density centrifugation. The cells were titrated with acid to a defined minimal pH value and retitrated with sodium hydroxide to normal pH (7.4 +/- 0.1) two times. After each of the two acid loadings, which were done at 37 degrees C (normothermia) and 43 degrees C (hyperthermia) the so-called specific filtration time (FZsp) is determined with 5 microns Nuclepore membranes under 4% hematocrit. FZsp is a measure for the relative flow resistance of the red blood cells they have with the filtering membrane. FZsp was found to be irreversibly increased by the twofold acid load. The effect increases with decreasing pH and increasing temperature. Hydrochloric acid has a greater effect than lactic acid. PMID- 2923520 TI - [Psychosocial aspects and rehabilitation problems of patients with tumors of the ORL region with special reference to laryngectomees]. AB - The operational therapy of malign tumours in the ORL is often connected with visible larger tissue organ lesions respectively. By this reason intensive efforts regarding comprehensive rehabilitation are necessary with the aim of overcoming the multiple impairments of familiar, social and occupational life. It is demonstrated with making inquiries concerning tight cooperation between patients, physicians, relatives, speech therapists and rehabilitation centres by example of laryngectomees as a premise for an successful reincorporation into a normal life. PMID- 2923521 TI - [Integration of malignant tumors of the head and neck region into the strategy of cancer control in the GDR]. AB - Mainly caused by an increase of carcinomas of the mouth and of the pharynx, the incidence of malignant tumours of the head and neck increased continuously, the incidence of these tumours has doubled in males. During the last twenty years, the age distribution clearly points the younger group of patients. In addition, the percentage of advanced tumours stages III and IV are increased. A more unfavourable prognosis with an increased mortality results despite of improved therapeutic techniques. The ways how to influence this development are discussed to reach the same positive situation as in total cancer treatment in the GDR. PMID- 2923522 TI - Assessment of phenotype of blood lymphocyte subsets prior and after PWM stimulation in patients with lung carcinoma. AB - Surface phenotypes of peripheral blood lymphocytes of lung cancer patients and those of two control groups were assessed by means of indirect immunofluorescence with monoclonal antibodies, prior and after 10 day pokeweed mitogen (PWM) in vitro stimulation. There was no significant alteration in pan T cell per cent values prior and after mitogen stimulation in all groups tested. CD4+ cells in lung cancer group were however significantly decreased as compared to blood donor group (37.3% vs 44.9%, p less than 0.05). This decline was even more pronounced in III/IVo stage of tumour progression according to TNM classification (36.8%, p less than 0.05). These changes, however were not cancer specific, because similar decrease of CD4+ cells was seen in a group of patients with nonneoplastic lung conditions (35.7%, p less than 0.01). Following 10 day PWM culture per cent values of CD4+ cells did not change significantly. The assessment of CD8+ lymphocytes has shown marked differences in two subgroups of lung cancer, namely in II (17.4%) and III/IV (26.2%) of tumour progression (p less than 0.05), which returned to normal values following PWM culture. CD4/CD8 ratio was distinctly depressed in cancer patients in relation to donors. The evaluation of surface markers of B lymphocytes activated cells and monocytes did not show significant alterations in all groups examined. Per cent of HNK1+ cells was heightened in cancer group, especially in III/IV stage of tumour progression in relation to donors (21.7% and 22.8% vs 17.3%, p less than 0.05 respectively). PWM stimulation resulted in marked fall of HNK1+ cells to values corresponding to those in donor group. This study indicates some alterations in per cent values of blood lymphocytes subpopulations belonging mainly to T cell lineage in lung cancer patients linked to tumour staging which only partially return to normal following PWM stimulation. PMID- 2923523 TI - [The effect of air pollutants on the incidence of lung tumors in the GDR]. AB - On the basis of the data from the National Cancer Registry in the GDR an investigation was made, concerning the relationship between exposure to different levels of air pollution and lung cancer incidence. Estimates for the exposure to major factors of air pollution as sulfur dioxide, sedimentation dust and a global air index were calculated for each county of the GDR. The statistical comparison of these data with respect to the age-adjusted incidence rates of the corresponding counties for the time period 1978 to 1982 have not shown any differences neither in man nor in woman. On the other side a positive correlation to the per caput consumption of cigarettes was found. PMID- 2923524 TI - Comprehensive cancer centres in The Netherlands. PMID- 2923525 TI - Organization of cancer care in the German Democratic Republic. PMID- 2923526 TI - Enhancement of hepatic tumors induced by N-nitrosodimethylamine in female toads Bufo regularis by oestrone. AB - The effect of oestrone on hepatic tumours induced in the female toads Bufo regularis by N-nitrosodimethylamine (DMNA) was evaluated. Injecting the toads with DMNA induced hepatocellular carcinomas in 17% comparable with 23% in toads injected with DMNA plus oestrone. These results show that oestrone insignificantly enhanced the tumour formation. Oestrone alone induced hepatic tumours in only 4 cases and was considered as a weak initiator. PMID- 2923527 TI - Posterior tibial tendon transfer in spastic equinovarus. AB - Twenty-eight posterior tibial tendon transfers through the interosseous membrane were performed to correct spastic equinovarus. All patients improved their gait, and 82% discarded their brace. Foot striking at the beginning of the stance phase was good or satisfactory in 82%; 68% had a neutral position of the heel. The overall score was good in 68%, satisfactory in 21%, and poor in 11%. The main requirements for obtaining good results with this type of transfer are: no fixed varus deformity preoperatively, age at operation between 5 and 10 years, and reinsertion near the midline of the foot. PMID- 2923528 TI - Value of cerclage fibreux for the Keller-Brandes procedure. AB - In the last 15 years Keller-Brandes operations have been performed in the Orthopedic Hospital Vienna-Speising, with and without cerclage fibreux. We were able to compare both methods in a long-term follow-up study and to check the function of the fibrous cerclage reducing the first intermetatarsal angle. The results of the random follow-up study of 100 patients show impressive advantages of the cerclage fibreux, objectively and subjectively, up to high intermetatarsal angles, which formerly were treated by osteotomies. PMID- 2923529 TI - Operative therapy for recurrent shoulder dislocation with special regard to long term clinical and radiological results using M. Lange technique. AB - Besides a general description of the operative techniques for the management of recurrent shoulder dislocation, a full description of the M. Lange procedure is given. We offer reasons for its variation from original methods and suggest limiting its indications with regard to clinical and radiological long-term results. After an average postoperative period of 13.5 years, clinical and radiological results of 21 shoulders in 20 patients were determined. In 19 of the 21 cases patients reported outstanding-to-satisfying postoperative results. Real postoperative redislocation was found in only one case, but striking radiological signs of osteoarthritis were seen in 57%. Despite the lack of comparable results, this should be taken into consideration in choosing an adequate operative procedure. PMID- 2923530 TI - Biomechanical analysis of hip function after Chiari pelvic osteotomy. AB - The reasons are discussed for differences in functional results of the pelvic osteotomy after Chiari, regardless of the fact that the CE and AC angles were equal in all patients. When lateralization and distal displacement of the greater trochanter were performed in addition to the pelvic osteotomy, the functional results proved to be better. Biomechanical analysis of the relationship between gluteal force and body weight revealed that these relations change; in all examined cases where lateralization and distal displacement of the greater trochanter were performed, the relationship proved postoperatively to be considerably more favorable. In the same group of patients, the relationship between the force of reaction and body weight was also changed after surgery. Therefore, lateralization and distal displacement of the greater trochanter are important factors for the undisturbed functioning of a hip; in all examined patients the functional results were better when lateralization and distal displacement of the greater trochanter were performed. PMID- 2923531 TI - Genu recurvatum due to partial growth arrest of the proximal tibial physis: correction by callus distraction. Case report. AB - The formation of a genu recurvatum after partial growth arrest of the proximal tibial physis is uncommon. This contribution deals with the case of a 16 years old male patient who after a direct injury to the proximal tibia four years ago showed a genu recurvatum of 18 degrees. An incomplete upper tibial corticotomy was performed and a hinge type de Bastiani fixator applied. The deformity was corrected at a distraction rate of one millimetre a day. The corticotomy gap filled with callus during the distraction process. The advantages of this concept are omision of iliac crest grafts, maintainance of a full range of knee motion with partial weight bearing during distraction and determination of the final degree of correction with the aid of proper radiographs. PMID- 2923532 TI - Radiological diagnosis of cervical trauma at the level C7/T1. AB - After a car accident a 23-year-old man was found to have rotational luxation of the cervical spine at the level C7/T1. The diagnosis was suspected from indirect signs on the ap X-ray and subsequently confirmed by conventional lateral tomography. Neurological symptoms were not present. Magnetic resonance imaging demonstrated dorsal protrusion of the intervertebral disc. PMID- 2923533 TI - Infection management in total hip replacement. AB - Early diagnosis and determined management of infection after hip replacement are the prerequisites for good end results. Infections that manifest themselves during the first 6 weeks after a prosthetic implant can be mastered by local debridement. The implant can thus be saved, and the functional performance as well. Infections that appear after this 6-week period may require temporary removal of the implant in order to control the infection. When the clinical aspects and laboratory data indicate the infection is under control, the hip endoprosthesis can be reimplanted with a very low rate of recurrence. The method applied for removal of implants and bone cement is of utmost importance for the final results, and a extremely diligent surgical technique is the basis for long term management of infection and good functional performance. Resection arthroplasty is not the treatment of choice anymore for infected hip prostheses and should be restricted to special cases. PMID- 2923534 TI - Cancellous bone and mechanical strength of the femoral neck. AB - Twenty pairs of dried macerated femora were submitted to progressive, physiologically oriented loading. The aim of this work was to determine the role of trabecular bone, the importance of the bone mineral density of the femoral shaft, and the importance of the Singh index in the mechanical strength of the femoral neck. By means of an original technique, the influence of both the principal tensile and secondary compressive trabecular groups on the mechanical strength to bending stress has been demonstrated. The artificial destruction of these trabecular groups is responsible for a loss of strength of more than 50% in varus angulation while it has practically no effect in valgus angulation. On the other hand, the mechanical strength of the femoral neck is better correlated with the bone mineral density of the femoral shaft (r = 0.74) than with the Singh index (r = 0.50) or with age (r = 0.15). PMID- 2923535 TI - Early changes in the ground substance of articular cartilage in experimental hemarthrosis in dogs, measured by the fixed-charge density method. AB - This work presents early findings in the articular cartilage of dog knees in experimental hemarthrosis produced by injections of whole blood, red blood cells, white blood cells, serum, and iron citrate. The effect of coagulation and synovectomy was also studied. The fixed-charge density determination has proved to be a reliable, easy, and rapid method for finding - very early in the process quantitative changes in cartilage ground substance. Changes in the proteoglycan (PG) content of articular cartilage matrix take place after a certain duration and intensity of hemarthrosis, after which loss of ground substance is repeatedly and consistently observed. After some time (6 months, and culminating after 14 months in our study) a reparative reaction takes place. In experimental hemarthrosis of longer duration this healing reaction seems to be overwhelmed by the degrading forces, with probable further evolution to the full-blown pathology. The cellular components of the blood seem to play a major role. Prophylactic synovectomy seems to be effective only in preventing further bleeding. Coagulation of the intra-articular blood does not alter its deleterious effect. Finally, a small iron ligand alone, although proven in vitro to penetrate into cartilage, is not capable of producing matrix changes. PMID- 2923536 TI - Results of screw osteosynthesis in spondylolysis and low-grade spondylolisthesis. AB - Nineteen patients with spondylolysis and low-degree spondylolisthesis were treated with bone grafting and osteosynthesis of the pars defect with the Morscher hook screw (16 cases) or with Buck's procedure (three cases). Eighteen patients had a follow-up examination. In the age-group 9-16 years (ten patients) there were 80% excellent or good results with fusion, whereas in the adult group (eight cases) the majority had poor results. It seems that the operative techniques which we applied are useful in juvenile patients; adults require a more reliable fixation. PMID- 2923537 TI - 21st Walter J. Zeiter lecture. Physiatric practice: an evolving "system" of care. PMID- 2923538 TI - Rehabilitation outcome after anoxic brain damage. AB - Outcome was analyzed in a group of 31 patients who were comatose for more than 24 hours after cardiopulmonary arrest and were thereafter referred for inpatient rehabilitation. Seventeen regained functional ambulation, 20 regained oral communication, and 13 regained full independence in activities of daily living. Two regained their approximate previous cognitive level, and one regained his previous level of employment. These outcomes are strikingly inferior to those of patients with prolonged coma after craniocerebral trauma who were hospitalized in the same center during the same period. Both age and coma duration were correlated with outcome. The relatively better outcomes were seen in patients who were 25 years or younger at the time of anoxic injury, and whose coma lasted less than 24 hours. PMID- 2923539 TI - Evoked potential assessment: utility in prognosis of chronic head injury. AB - Brainstem auditory evoked potentials (BAEP) and somatosensory evoked potentials (SSEP) were performed on 29 patients an average of 12.4 months after traumatic brain injury (TBI). The study purpose was to predict long-term outcome in chronic TBI patients by using multimodality evoked potentials (MEP), the Rancho Los Amigos Scale (RLAS), and other clinical parameters. Neither the BAEP nor SSEP correlated significantly with the cognitive level on the RLAS at the MEP study approximately one year after TBI (RLAS1). Only 11.7% of RLAS1 could be predicted by the combined study of BAEP and SSEP. BAEP and SSEP obtained about one year after TBI jointly had a 15% predictive power of the long-term follow-up RLAS score obtained 18 months after performance of the MEP (RLAS2). Stepwise regression analysis showed that the best predictive indicator of the status of long-term outcome was RLAS1 which alone can predict 60% of long-term outcome. The predictive value of combinations of RLAS1 and age improved prediction of long term outcome to 66.8%, and the combination of RLAS1, age, and SSEP further increased the value to 72%. Perhaps the MEPs were relatively insensitive in reflecting the patient's adaptation to fixed neuronal damage since patients can perform higher cognitive function by adaptation through behavioral modification and cognitive retraining despite little structural improvement. This adaptation would result in a discrepancy between MEP and RLAS scores in the late chronic phase. PMID- 2923540 TI - Cortical somatosensory evoked potentials: effects of positional changes. AB - Supine and sitting lower extremity cortical somatosensory evoked potential (CSEP) examinations were performed in 30 healthy volunteers to establish normal values and to determine variations in SEP parameters caused by positional changes, side of stimulation, and the influence of height. CSEPs were recorded at Cz'-Fz (10-20 international EEG system) after stimulation of the saphenous, peroneal, and sural nerves at the ankle. Each nerve was tested in the supine and sitting positions. CSEP P1, N1 latencies and P1 - N1 amplitudes were recorded. The mean values of these parameters and side-to-side differences were determined for both positions. Parameter changes between the two positions were also determined. No statistically significant difference was found when comparing supine and sitting, or side-to-side values (p greater than 0.05). Regression analyses of P1 latency vs height revealed a significant positive correlation for both positions (p less than 0.0001-0.0045). Mean P1 and N1 latencies (msec) +/- 1SD, and mean P1 - N1 amplitudes (microV) +/- 1SD are as follows: peroneal nerve (n = 119) P1 = 39.5 +/ 2.98, N1 = 48.2 +/- 3.79, P1 - N1 = 1.41 +/- 0.81; sural nerve (n = 119) P1 = 41.3 +/- 4.03, N1 = 50.9 +/- 4.57, P1 - N1 = 1.31 +/- 0.61; saphenous nerve (n = 119) P1 = 41.5 +/- 4.02, N1 = 50.4 +/- 4.10, P1 - N1 = 0.87 +/- 0.30. The normative data generated by this study will help clinicians to distinguish normal variations in lower extremity CSEP parameters.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2923541 TI - Electrodiagnosis of mild carpal tunnel syndrome. AB - Electrophysiologic tests have been reported to detect mild carpal tunnel syndrome (CTS). Such tests include (i) absolute palmar latency of median wrist segment; (ii) comparison of median and radial distal sensory latencies in digit I; (iii) comparison of median and ulnar distal sensory latencies in digit IV; (iv) comparison of median and ulnar palmar latencies; (v) comparison of median and ulnar sensory potential amplitudes in digits II and V. To clarify the clinical utility of these tests, the parameters of all five tests were determined across four carefully established patient subgroups: group A, controls; group B, CTS referrals with normal nerve conduction studies (NCS) and normal needle electromyography (EMG); group C, CTS referrals with abnormal NCS and normal EMG; group D, CTS referrals with abnormal NCS and abnormal EMG. Special attention was focused on patients in group B who represent the diagnostic dilemma. In group B, tests ii and iii each yielded abnormal results in 44% of hands, while the combination of tests ii and iii yielded abnormal results in 51% of hands. PMID- 2923542 TI - Electrophysiologic recovery of acute conduction block of rat tail nerve. AB - The recovery of experimental compression neuropathy with prolonged conduction block of the caudal nerve was studied electrophysiologically in 48 adult Sprague Dawley albino rats divided equally into six groups. The pressure applied in groups A, B, C, D, E, and F was approximately 20kg/cm2 for 20 minutes, 20kg/cm2 for 10 minutes, 20kg/cm2 for 5 minutes, 10kg/cm2 for 20 minutes, 20kg/cm2 for 10 minutes, and 10kg/cm2 for 5 minutes, respectively. The motor nerve conduction velocity (NCV) and the amplitude of the evoked compound muscle action potential (CMAP) were measured before and periodically after nerve compression. The period of initial complete block was significantly longer in the high pressure groups than in the lower ones, and also significantly longer in the nerves compressed for 20 minutes than for those compressed for five or ten minutes. Thus, the severity of conduction block seems to be related to both pressure and duration of compression. Once the conduction block began to recover, the recovery rate of conduction block (recovery rate of amplitude ratio of CMAP, proximal/distal) was not significantly different. The recovery rate of demyelinative lesion (NCV recovery rate) was also not significantly different among the six groups. The degree of compression seems to determine the severity of the initial conduction block, but not the subsequent recovery rate of conduction. PMID- 2923543 TI - Early smooth horizontal eye movement: a favorable prognostic sign in patients with locked-in syndrome. AB - Locked-in Syndrome (LIS) is a rare clinical entity consisting of quadriplegia, paralysis of lower cranial nerves, mutism, and bilateral paresis of horizontal gaze. The prognosis is usually poor. Most patients who do survive have severe residual impairment or develop chronic LIS. Review of the literature shows that recovery has been reported but not systematically studied, particularly with respect to early prognostic signs. We report a case of LIS with bilateral pontine infarctions shown by MRI. Severe neurological deficits included quadriplegia, paresis of horizontal gaze, facial paralysis, and bulbar palsy. Horizontal eye movements were present and smooth by the second week after onset. The patient had almost full functional motor recovery within four months, after a comprehensive rehabilitation program. Fourteen other reported cases of LIS with full recovery had documented recovery of lateral gaze in the early stage. In addition, smooth horizontal gaze is the most frequent activity in incomplete LIS. Early recovery of horizontal eye movement may indicate that the brain lesion is limited and may be a good prognostic sign in LIS. PMID- 2923544 TI - Radial nerve palsy: a complication of walker usage. AB - A patient with diabetic peripheral neuropathy experienced the acute onset of a proximal radial nerve palsy after prolonged use of a walker. Nerve conduction and electromyographic studies confirmed an isolated, severe neurapraxic lesion distal to branches innervating the triceps and anconeus muscles. The acute onset and severity of this lesion suggests that it was caused by mechanical compression of the radial nerve as it exits the spiral groove. Radial mononeuropathy has been reported in conjunction with muscular effort of the triceps muscle. Previous case studies and a review of the literature are discussed. Awareness of this complication in patients using walkers and wheelchairs is important for prevention and diagnosis in rehabilitation. PMID- 2923545 TI - Isolated lateral pectoral nerve injury: trauma from a seat belt. AB - A 35-year-old man sustained an isolated injury to the lateral pectoral (anterior thoracic) nerve as the result of a seat belt injury. This resulted in atrophy of the clavicular head of the pectoralis major. Electromyography confirmed localized abnormal findings in this muscle and an isolated lesion of the lateral pectoral nerve, the first reported case of such a lesion. PMID- 2923546 TI - "Bedside" test of static rear stability of occupied wheelchairs. AB - The assessment of static stability can be helpful in wheelchair prescription and adjustment, but ordinarily requires a tipping platform. We developed a simple "bedside" test of rear wheelchair stability, using a goniometer and a plumb line. The angle of the wheelchair handle while the occupied wheelchair was on a level surface was subtracted from the angle measured while the occupied chair was balanced over the rear axle. The intraobserver and interobserver reliability and the validity in comparison with platform testing were assessed by studying 30 patient-occupied wheelchairs. There was a high correlation (r = 0.93, p less than 0.001) between the values obtained from the beside and platform tests and no significant difference between them. Intraobserver and interobserver reliabilities were 0.87 (p less than 0.001) and 0.94 (p less than 0.001). There was no significant difference between the first and second test values done by a single observer; the mean difference (+/- 1SD) between observers, 1.3 degrees (+/ 1.6 degrees), was small but statistically significant. The bedside test is simple, reliable, valid, and suitable for use as a screening test for the platform assessment of rear stability. PMID- 2923547 TI - Early events in arenavirus replication are sensitive to lysosomotropic compounds. AB - Lysosomotropic compounds (ammonium chloride, chloroquine, amantadine, monensin) effectively inhibited the replication of Pichinde, Mopeia, and Lassa viruses in BHK-21 and Vero cells. The inhibitory effect was dependent upon the time of drug addition and was most effective when the drugs were added 1 h before the viral adsorption. The drugs had no direct effect on the infectious viruses nor on adsorption of the arenaviruses. These results suggest that the arenaviruses enter cells by adsorptive endocytosis with the participation of acidic intracellular vesicules. PMID- 2923548 TI - Studies on poxvirus infection in cats. AB - The development of clinical disease and the pathogenesis of cowpox were studied in domestic cats inoculated by a variety of routes. Intradermal titration in two cats demonstrated that as little as five pfu of cowpox virus caused a primary skin lesion. Intradermal inoculation of greater than or equal to 10(5) pfu cowpox virus resulted in severe systemic disease. Large amounts of virus (greater than or equal to 10(3) pfu/g) were isolated from skin lesions and the turbinates of cats killed at eight and 11 days post-inoculation (dpi). Lesser amounts of virus (congruent to 10(2) pfu/g) were isolated from lymphoid tissues and the lung, and small amounts of virus were isolated from various other tissues. A white cell associated viraemia was detected from 5 dpi onwards. Skin scarification with 10(3) or 50 pfu cowpox virus enabled reproduction of the naturally-acquired disease. Cat-to-cat transmission was demonstrated from cats inoculated by skin scarification, but caused only subclinical infection in sentinel cats. Oronasal inoculation resulted in transient coryza and milder generalized disease than skin inoculation, and no transmission to sentinel cats. Preliminary investigations showed vaccinia virus (Lister strain) to be of low infectivity in cats while inoculation of ectromelia virus (Mill Hill strain) did not cause any clinical signs. PMID- 2923549 TI - Physical mapping of a genome of equine herpesvirus 2 (equine cytomegalovirus). AB - The genome of a low equine cell passage equine herpesvirus 2 was partially cloned and physical maps for the restriction endonucleases BamHI, EcoRI, HindIII, and SalI determined. The genome length was estimated to be 192 kilobase pairs (kbp) and no evidence of isomerization was found. Two separate repeat structures were detected: 18 kbp direct terminal repeats; and an unrelated second pair of short internal, indirect repeats at 0.20 and 0.75 map units. Such a genomic structure does not appear to have been reported amongst the herpesviruses--all the genomes that do not isomerize either have repeat structures only at the termini, or if present internally, have only direct repeats. PMID- 2923551 TI - New spatula for epiretinal membrane separation. PMID- 2923550 TI - Cryotherapy for retinopathy of prematurity. PMID- 2923552 TI - Infiltrative keratitis associated with disposable soft contact lenses. Case reports. PMID- 2923553 TI - Vibrio vulnificus corneal ulcer. Case reports. PMID- 2923554 TI - Retinitis pigmentosa and branch retinal artery occlusion with anticardiolipin antibody. Case report. PMID- 2923555 TI - Monozygotic twins discordant for Duane's retraction syndrome. Case report. PMID- 2923556 TI - The Hsiao study. A personal perspective. PMID- 2923557 TI - Long-term evolution of astigmatism following planned extracapsular cataract extraction. AB - Sixty-six eyes of 66 patients undergoing planned extracapsular cataract extraction with interrupted 10-0 nylon suture wound closure were followed up prospectively for three years following surgery to evaluate the long-term evolution of postoperative astigmatism. The study examined the period beginning three months postoperatively, well after all suture cutting was completed, a point often considered to represent "final postoperative astigmatism." For the group as a whole, the induced astigmatism measured at three months was not stable, but gradually shifted 0.69 diopter toward against-the-rule astigmatism. Three specific patterns of evolution of postoperative astigmatism were identified, depending on the amount of induced astigmatism found at three months. The data revealed that it was not possible to consistently induce with-the-rule astigmatism, although permanent against-the-rule induced astigmatism could be produced. The long-term evolution of postoperative cataract wounds toward more against-the-rule astigmatism seen in this study was not affected by the number of intact nylon sutures. Proper evaluation of any technique to modify postoperative astigmatism must consider the long-term evolution of the cataract wound. PMID- 2923558 TI - Ultraviolet light exposure and risk of posterior subcapsular cataracts. AB - Posterior subcapsular (PSC) cataracts are a visually disabling form of cataract and account for 40% of surgical cases. Although PSC opacities may occur following intraocular inflammation, trauma, or use of steroids, the cause is often unknown. A case-control study was undertaken to investigate the role of exposure to ultraviolet light in the B range (UV-B) and other potential risk factors for the development of PSC cataracts. Surgical PSC cataract cases from a large rural ophthalmic practice on the lower eastern shore of Maryland were matched with phakic controls without PSC cataract changes from the same geographic area by age, sex, and referral pattern. All patients with PSC opacities who underwent cataract surgery in a 12-month period were chosen. One hundred sixty-eight cases and 168 controls were interviewed regarding sunlight exposure, drug use, occupational history, history of diabetes, hypertension, and other diseases. Matched-pairs analyses indicated that a history of relatively high exposure to UV B was associated with increased risk of PSC cataracts. The association of PSC cataracts with steroid use and diabetes was reconfirmed. Subjects with blue eyes and less than high school education were also at increased risk for PSC cataracts. Smoking and hypertension were not found to be PSC cataract risk factors. These data suggest that UV-B exposure may be an important risk factor for PSC cataracts. PMID- 2923559 TI - Photic retinopathy from the operating room microscope. Study with filters. AB - A patient's blind phakic eye with clear media, the subject of previous light exposure studies, was exposed for 60 minutes to light from a standard operating room microscope (Zeiss OpMi-6) filtered through an infrared filter. A typical acute photic retinopathy lesion was produced. Two and a half months later, the eye was exposed for 60 minutes to light filtered simultaneously through an ultraviolet filter and an infrared filter. Despite blocking both the ultraviolet and infrared light, and despite reducing the overall light energy by approximately one fourth because of the combination of filters, a typical acute photic retinopathy lesion was produced by the transmitted light, the energy of which was essentially all within the visible spectrum. PMID- 2923560 TI - Acute comitant esotropia in children with brain tumors. AB - If acute onset of esotropia is comitant, its cause is generally believed to be benign. Although this is, by and large, true, it is now clear that acute comitant esotropia may be associated infrequently with central nervous system illness. We describe six children who presented with acute onset of comitant esotropia, and who were found to have tumors of the brain stem or cerebellum. Four of the patients underwent strabismus surgery after appropriate neurologic and neurosurgical treatment was completed. In none of these patients was ocular motor fusion reestablished. PMID- 2923561 TI - Ocular pneumoplethysmography can help in the diagnosis of giant-cell arteritis. AB - We compared the results of ocular pneumoplethysmography in nine patients who had a temporal artery biopsy (TAB) diagnostic of giant-cell arteritis with results of ocular pneumoplethysmography in nine patients with normal TAB results and 112 patients with anterior ischemic optic neuropathy or central retinal artery occlusion assumed to be nonarteritic. The mean +/- SD ocular pulse amplitude with ocular pneumoplethysmography was 3.9 +/- 1.8 mm in the group with abnormal TAB results and 10.6 +/- 4.0 mm in the group with normal TAB results. Every patient with abnormal TAB results had an average calculated ocular blood flow less than 0.60 mL/min, while only one patient with normal TAB results fell in this range. The average calculated ocular blood flow had a sensitivity of 100% and a specificity of 93.4% in the diagnosis of giant-cell arteritis, with a diagnostic accuracy of 93.9%. These results rival the diagnostic accuracy of the erythrocyte sedimentation rate and TAB results. PMID- 2923562 TI - Indirect optic nerve trauma. AB - This report summarizes the details of 33 personal cases of the important but uncommon entity of posttraumatic optic neuropathy, seen during an 11-year interval. Victims were predominantly young males, and bicycles proved the most common source of injury. Severity of visual loss correlated poorly with level of consciousness and presence of craniofacial fractures. Optic canal fractures were found in only seven of the patients. Vision improved in five of 25 untreated patients, one of four treated with corticosteroids, and three of four treated with corticosteroids and transethmoidal decompression of the optic canal. No patients lost vision after their initial examination. Two of six initially blind eyes regained some vision. Management of these injuries is controversial. Hospitals should designate physician teams that should develop and implement a treatment plan for traumatic optic neuropathies. PMID- 2923563 TI - Cryptogenic oculomotor nerve palsy. The need for repeated neuroimaging studies. AB - Five children between ages 3 and 17 years developed slowly progressive oculomotor nerve palsies. No cause was found on initial clinical or neuroradiologic investigations. Subsequent computed tomography or 1.5-T magnetic resonance imaging revealed a mass along the course of the involved oculomotor nerve in three of the five cases. The clinical and radiologic characteristics of these tumors are consistent with the diagnosis of schwannoma or, less likely, meningioma. Children with acquired oculomotor nerve palsies of initially unknown etiology should undergo imaging every two years with the expectation of eventually detecting a small tumor somewhere along the course of the oculomotor nerve. PMID- 2923564 TI - Subretinal fluid stimulation of retinal pigment epithelial cell migration and proliferation is dependent on certain features of the detachment or its treatment. AB - Subretinal fluid was collected without contamination by blood by placing capillary tubes within drainage sclerotomies when retinal reattachment surgery was performed. All samples (N = 24) stimulated retinal pigment epithelial (RPE) cell migration and proliferation, but a wide range of activity existed (migration, 27.5% to 322.5% above baseline; proliferation, 7.5% to 318.3% above baseline). The correlation between migration- and proliferation-stimulating activity was not strong, suggesting the possibility that different agents are responsible for each. Several variables were examined for correlation with each activity, including age and sex of the patient; extent, duration, and height of the detachment; protein content of the fluid; and amount of cryopexy. It was found that proliferation-stimulating activity increased with the extent of detachment and duration of detachment, while migration-stimulating activity correlated best with amount of cryopexy given before drainage. These data suggest that retinal cryopexy enhances RPE cell migration activity in subretinal fluid, while RPE proliferation activity increases with the size and duration of detachment. PMID- 2923565 TI - Malignant melanoma of the iris in xeroderma pigmentosum. AB - Xeroderma pigmentosum is an autosomal recessive, precancerous dermatosis caused by defective repair of ultraviolet-damaged DNA. Characterized clinically by progressive cutaneous pigmentary alterations and tumorigenesis, it serves as a model for ultraviolet carcinogenesis. We describe the clinical and histopathologic findings in a 31-year-old woman with xeroderma pigmentosum and a massive iris melanoma of the left eye. Histologic examination following enucleation revealed diffuse iris replacement by spindle and epithelioid cells with extension into the trabecular meshwork. Evidence of direct extraocular extension was absent, and a metastatic evaluation showed no abnormalities. To our knowledge, this is the first reported case of xeroderma pigmentosum complicated by melanoma of the iris. It provides further evidence suggesting a role for sunlight exposure in the pathogenesis of uveal melanoma. PMID- 2923566 TI - Dextromethorphan protects retina against ischemic injury in vivo. AB - Retinal ischemia was induced in rabbits by increasing intraocular pressure above systolic blood pressure for 60 or 75 minutes, and retinal function was monitored by electroretinography. Pretreatment with intravenous dextromethorphan, a nonprescription antitussive and selective antagonist of N-methyl-D-aspartate receptors, enhanced greatly the post-ischemic recovery of b-wave amplitude. Dextromethorphan may prove to be useful clinically in the management of retinal ischemic disease. PMID- 2923567 TI - Vitreoperfusion. A new approach to ocular ischemia. AB - No satisfactory treatment is available to supply the metabolic needs of the retina in vascular occlusion. Consequently, necrosis occurs. We devised vitreoperfusion, a technique of perfusing the vitreous cavity after vitrectomy lensectomy with selected fluids containing glucose and oxygen. We tested whether vitreoperfusion could protect the retina from severe combined retinal and choroidal ischemia. An intraocular pressure of 170 mm Hg was induced in each eye of nine cats for up to four hours, and simultaneously one eye of each cat underwent vitreoperfusion. After one week, histopathologic examination revealed retinal atrophy and dissolution in untreated eyes but not in eyes treated with vitreoperfusion. To our knowledge, such severe ischemia has never been treated successfully before. Vitreoperfusion is a potential treatment modality in various forms of ocular ischemia. Additional studies are warranted to refine the technique and determine any clinical applicability. PMID- 2923568 TI - Erbium-YAG laser surgery on experimental vitreous membranes. AB - We used a pulsed erbium-YAG laser emitting in the midinfrared region (2.94 microns) to cut experimental vitreous membranes in rabbits via an intraocular fiberoptic delivery system. Thirty-four membranes were cut at distances of 500 to 3600 microns from the retina. All 34 of the membranes treated were effectively cut. Sixteen cases had no evidence of retinal injury, including one in which the membrane was only 800 microns from the retina. Retinal injuries in the remaining cases consisted of small (less than 300 microns) retinal burns and hemorrhages. In 94% of the cases with retinal injury, the fiberoptic was within 2000 microns of the retina. We conclude that a pulsed erbium-YAG laser allows near tractionless cutting of vitreous membranes and may have potential for clinical use if further studies show it to be efficacious and safe near the retina. PMID- 2923569 TI - Massive follicular lymphoid hyperplasia in experimental allergic conjunctivitis. Local antibody production. AB - Acute and recurrent allergic conjunctival reactions were induced in guinea pigs by repeated conjunctival applications of fluoresceinyl ovalbumin (FL-OA) for up to 30 months. Early type I conjunctival reactions developed 11 to 25 days after the initial conjunctival exposure to FL-OA. Continuous topical challenges during a six- to 30-month period caused a variety of reactions, including papillary changes and massive hyperplasia of the conjunctival-associated lymphoid tissues. Hyperplasia of lymphoid tissues was induced during a shorter period (two to five months) with a mixture of FL-OA and phorbol ester. Culture fluid from hyperplastic conjunctival lymphoid tissue showed a ratio of IgG1/IgG2 antibody production of up to 15. A low level of recurrence of type I reactivity, after an initial desensitization phenomenon due to a loss of reactive mast cells, correlated with prominent follicular hyperplasia of the conjunctival-associated lymphoid tissue. PMID- 2923570 TI - The effects of freezing and antibiotics on the viability of Acanthamoeba cysts. AB - The effects of cryotherapy and antibiotics (paromomycin, neomycin, or propamidine isethionate) on the viability of Acanthamoeba polyphaga and Acanthamoeba castellani cysts were studied in vitro. Either cryotherapy or exposure to antibiotic led to a decrease in the number of viable A castellani detected; A polyphaga showed variable response to the antibiotics tested. The combination of cryotherapy and antibiotic therapy was more cysticidal than either modality alone and eliminated detectable viable organisms in five of six experiments. Of the antibiotic solutions tested, paromomycin (15 mg/mL) was the most effective. PMID- 2923571 TI - Ocular lymphoid hyperplasia. PMID- 2923572 TI - The five-flap technique for blepharophimosis. AB - The correction of epicanthus associated with blepharophimosis is a difficult surgical problem. Most commonly used techniques, such as the Mustarde technique, require meticulous measurements, and their theoretical geometric basis and flap designs are often confusing. We present the five-flap technique utilizing logical flap design, which is a combination of a Y-to-V flap with double opposing Z plasties on the apex, that is well suited to this difficult problem. It is important to remove excess muscle and deep tissues underlying the flaps in the medial canthal region, which are present in blepharophimosis cases and contribute to the deformity in these patients. Medial canthal tendon resection and tucks or transnasal wiring are then performed. The technique has been utilized in 14 patients with a minimum of one year of follow-up over the past six years with good results. PMID- 2923573 TI - A modified slit lamp for examination of wheelchair-bound patients. AB - A standard slit lamp can be modified with readily available components to examine wheelchair-bound patients. This modification minimizes discomfort in transferring patients to an examination chair and may provide better patient positioning in some cases. In addition to saving staff time, this technique minimizes the disconnecting of intravenous tubing, drainage catheters, and similar appliances. The addition of a swivel extension to the base of the slit lamp allows the entire unit to slide between the arms of the wheelchair at a height that is comfortable for the patient. PMID- 2923574 TI - Comparison of arterial intimal clearances of LDL from diabetic and nondiabetic cholesterol-fed rabbits. Differences in intimal clearance explained by size differences. AB - Arterial intimal clearances of low density lipoproteins (LDL) from diabetic cholesterol-fed rabbits (D-LDL) and LDL from nondiabetic cholesterol-fed rabbits (N-LDL) were compared. In six experiments, D-LDL and N-LDL were isolated from a diabetic and a nondiabetic rabbit, were iodinated with 125I and 131I, respectively, were mixed, and were reinjected into the same two rabbits as well as into a normal rabbit. Fractional catabolic rates for D-LDL and N-LDL in normal rabbits were 0.065 and 0.074 h-1 (p less than 0.05), respectively. For five of the six pairs of LDL, the D-LDL was smaller than N-LDL as determined by gel filtration. The arterial permeability to N-LDL, when normalized for differences in arterial cholesterol content, did not appear to differ between diabetic and nondiabetic rabbits. The relative arterial intimal clearance (D-LDL/N-LDL) in arteries from diabetic and nondiabetic rabbits was inversely related to the relative molecular weight (D-LDL/N-LDL). For example, when the molecular weight of D-LDL was as low as 60% of that of N-LDL (i.e., the diameter of D-LDL was reduced 16%), the intimal clearance of D-LDL was 40% larger than that of N-LDL. When, on the other hand, molecular weights and diameters of the two LDL were similar, the intimal clearance was also quite similar. These results suggest that arterial intimal clearance of LDL from diabetic and nondiabetic cholesterol-fed rabbits is comparable unless the two types of LDL have a different size. PMID- 2923575 TI - Development of atherosclerosis in genetically hyperlipidemic rabbits during chronic fish-oil ingestion. AB - The evidence for a reduction in cardiovascular mortality from fish oil is based on epidemiologic observations. To test whether fish-oil supplementation influences the development of atherosclerosis, we treated Watanabe heritable hyperlipidemic rabbits (WHHL), an inbred strain that spontaneously develops atherosclerosis, with 2.5 ml of MaxEPA fish-oil concentrate daily and compared them to a control group fed unsupplemented rabbit chow. Serial cholesterol and triglyceride levels were monitored as were plasma lipid hydroperoxides. The animals were given fish oil from the time of weaning until 1 year of age, when they were sacrificed and their aortas were compared for the extent of atherosclerosis. No significant differences in the cholesterol or triglyceride levels were noted between the two groups. Fatty acid hydroperoxide levels were also similar and were noted to increase from weaning (1.0 +/- 0.7 microM) to the time of sacrifice (1.8 +/- 1.5 microM, p less than 0.01). Fish oil had no influence on the extent of aortic atherosclerosis (25% +/- 14% surface area for controls vs. 28% +/- 19% for treated, p = NS), plaque thickness, or plaque volume after 1 year. We conclude that fish oil does not reduce the levels of serum cholesterol, lipid hydroperoxides, or aortic atherosclerosis in WHHL rabbits. The hypothesis that fish oil protects against atherosclerosis was not supported by this study. PMID- 2923576 TI - Adipose tissue distribution and plasma lipoprotein levels in obese women. Importance of intra-abdominal fat. AB - Prospective studies have shown that excess abdominal fat is associated with an increased risk of coronary heart disease and related death. We used computed axial tomography (CAT) to assess the association between deep and subcutaneous abdominal adipose tissue and plasma lipoprotein levels in a sample of 52 premenopausal obese women aged 35.7 +/- 5.5 years (mean +/- SD). Whereas the plasma lipoprotein concentration were not significantly correlated with fat mass, the data obtained by CAT indicated that the absolute amount of deep abdominal fat was negatively correlated with high density lipoprotein cholesterol (HDL-CHOL) levels (r = -0.35, p less than 0.01), as well as with HDL-CHOL/low density lipoprotein (LDL)-CHOL, HDL-apoprotein-(apo) A-I/LDL-apo B, and HDL2-CHOL/HDL3 CHOL ratios (-0.32 less than or equal to r less than or equal to -0.40, 0.05 greater than p less than 0.01). Adipose tissue deposition at the mid-thigh region determined by CAT did not show any significant relationship with plasma lipoprotein levels. When subgroups of women with comparable ages and adiposity but with high and low intra-abdominal fat accumulation were compared, women with a high accumulation of intra-abdominal fat displayed significantly lower HDL-CHOL (p less than 0.001), HDL2-CHOL (p less than 0.001), HDL3-CHOL (p less than 0.01), and HDL-apo A-I (p less than 0.05) levels, as well as reduced HDL-CHOL/LDL-CHOL (p less than 0.01), HDL-apo A-I/LDL-apo B (p less than 0.05), and HDL2-CHOL/HDL3 CHOL ratios (p less than 0.05) in comparison with obese women with low accumulations of intra-abdominal fat.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2923577 TI - Homozygous familial hypercholesterolemia among French Canadians in Quebec Province. AB - Nineteen patients with homozygous familial hypercholesterolemia (FH) living at the time of the 1981 Canada census are the subject of this report. Their mean age at that time was 15, with a range of 1 to 26 years. All patients had extensive xanthomatosis but showed variable clinical manifestations of coronary heart disease (CHD); five (mean age, 21; range, 11 to 27 years) died from sudden death due to CHD. Plasma cholesterol levels varied more than twofold (557 to 1532 mg/dl). Variation in the concentrations of both plasma and low density lipoprotein cholesterol, as well as apolipoprotein B, were related neither to age at death from CHD nor to the clinical course of CHD. The mean high density lipoprotein cholesterol concentration (37 mg/dl) was lower than the mean value (49 mg/dl) in the control population (p less than 0.001). Both the clinical and biochemical features of this cohort are typical of homozygous FH. The prevalence of homozygotes among French Canadians in Quebec was approximately 1:275,000, and the minimum estimated frequency of heterozygotes was 1:270. In northeastern Quebec, the frequency of homozygotes was approximately 1:100,000, and the minimum estimated frequency of heterozygotes was 1:154. Only Afrikaaners in South Africa have correspondingly higher frequencies. PMID- 2923578 TI - A possible mechanism for accelerated atherogenesis in male versus female rats. AB - Dietary fat and cholesterol enter the circulation as chylomicrons. They are removed from the circulation by attachment to lipoprotein lipase located on the endothelial surfaces. As the result of lipoprotein lipase action, chylomicrons are partially hydrolyzed and then reenter the circulation as remnants, which are rapidly cleared by the liver. We investigated the fate of 3H-retinol- and 14C cholesterol-labeled chylomicrons injected into male and female rats. The disappearance curves of chylomicrons from the circulation were not significantly different in males and females, which suggests that translocation from plasma to endothelium is similar for both sexes. However, in male rats, the "dwell time" of chylomicrons on the endothelium was significantly prolonged. At 10 and 20 minutes after chylomicron injection, more label was found in the livers of female than male rats. The opposite was true for hearts. Male hearts contained significantly more endothelium-bound chylomicrons when compared with female hearts. This increase in dwell time may allow greater cholesterol deposition in the endothelium of male rats. The more rapid processing of chylomicrons was associated with a 300% greater postheparin lipoprotein lipase in female rats, which suggests a greater enzyme density at chylomicron attachment points on endothelium. PMID- 2923579 TI - Transendothelial transport of low density lipoprotein in association with cell mitosis in rat aorta. AB - Atherosclerosis is characterized by focal areas of lipid accumulation and intimal smooth muscle cell proliferation in large arteries. In vivo studies on rat aorta with Evans blue-albumin conjugate (EBA) have shown that there are preferential sites of increased permeability with an increased uptake of the conjugate. It has been shown that these blue areas are associated with a high endothelial cell turnover rate and an enhanced permeability to lipids. In a previous study, we demonstrated that 99% of endothelial cells in the mitotic (M) phase as identified by hematoxylin staining of the dividing nuclei exhibited EBA leakage and that these dividing cells accounted for 30% of all leakage sites. In the present study, experiments were performed on the thoracic aortas of 10 adult male Sprague Dawley rats to determine the statistical frequency of isolated leaks to Lucifer yellow-low density lipoprotein conjugate (LY-LDL) at the level of individual cells and to assess the relationship of such leaks to the cell turnover processes. Leakage of LY-LDL around individual endothelial cells was visualized by fluorescence microscopy, and cells in mitosis on the same specimens were identified by hematoxylin staining. Although endothelial cell mitosis is infrequent (0.034%), 80% of dividing cells in the M phase were associated with LY LDL leakage. These dividing cells accounted for 45% of all leakage spots. These findings lend support to our recent hypothesis that transiently open junctions surrounding the endothelial cells undergoing cell turnover provide pathways through which LDL enters the subendothelial space, resulting in lipid accumulation. PMID- 2923580 TI - Apoprotein E polymorphism and coronary artery disease. Increased prevalence of apolipoprotein E-4 in angiographically verified coronary patients. AB - Several studies have indicated that genetic polymorphism of apolipoprotein (apo) E is related to coronary artery disease (CAD). We therefore determined the apo E phenotype in 91 consecutive Finnish men with angiographically confirmed CAD. The apo E phenotype distribution differed significantly from that observed in the Finnish population (p less than 0.05). In the patient group, the frequency of the epsilon 4 allele was 0.324, which is 1.4-fold higher than in the normal Finnish population and twice as high as in other Caucasian populations. Serum lipoproteins and postheparin plasma lipase activities did not display any significant variation according to apo E phenotype. These studies confirm and extend, in a population with high epsilon 4 allele frequency, the previous data on the impact of the epsilon 4 allele on the risk of CAD and suggest that the high epsilon 4 allele frequency in the Finnish population may be one factor contributing to Finns' increased susceptibility to CAD. PMID- 2923581 TI - Use of 3H-cholesteryl linoleyl ether as a quantitative marker for loss of cholesteryl ester during regression of cholesterol-induced aortic atheromas in rabbits. AB - In this study, use was made of 3H-cholesteryl linoleyl ether (3H-CLE) to follow regression of aortic atheromatosis induced by feeding cholesterol to rabbits. After a 3-month induction period, the rabbits were divided into two groups with an attempt to match them by plasma cholesterol levels. They were injected with rabbit plasma labeled with 3H-CLE, and the baseline group rabbits were killed 10 to 12 days after injection. The experimental (regression) group rabbits were given rabbit chow containing 3% cholestyramine and were killed up to 330 days thereafter. Aortic 3H-CLE of both the baseline and the regression groups correlated highly with the plasma cholesterol levels at the time of injection of label. The radioactivity recovered in the aortas of the baseline and regression groups was not significantly different, indicating retention of label between day 12 and 330 days after injection. During that time, the mean aortic cholesteryl ester content decreased from 7.6 +/- 1.3 mg to 3.1 +/- 0.7 mg (p less than 0.01). The specific activity of 3H-CLE/cholesteryl ester determined in the aortic arch and the thoracic and abdominal aorta was significantly increased in all three regions examined in the regression group as compared to the baseline group. The present data show that 3H-CLE is retained in the atheromatous aorta for at least 330 days and that its use may add another dimension to the quantitative evaluation of regression of atherosclerotic lesions. PMID- 2923582 TI - Effect of lanthanum chloride on established atherosclerosis in the cholesterol fed rabbit. Mitral valve as a site for assessment of treatment effects. AB - The ability of lanthanum chloride (LaCl3) to retard the progression of established atherosclerosis was investigated in cholesterol-fed rabbits. Rabbits were initially maintained on a high-fat plus cholesterol-supplemented diet for 10 weeks to induce lesions and were then changed to a low-fat diet or a low-fat diet supplemented with LaCl3 for an additional 24 weeks to permit their serum cholesterol levels to normalize. LaCl3 did not affect the rate at which serum cholesterol levels returned to normal. The dose of LaCl3 was approximately 30 mg/kg body weight/day. In comparison with controls, LaCl3-treated rabbits exhibited histologically less severe coronary artery and mitral valve atherosclerosis. Lesion severity in the carotid arteries was unaffected by LaCl3 treatment. Although statistically significant, the salutary effects of LaCl3 were relatively small. The data support the hypothesis that calcium antagonists can retard the progression of established atherosclerotic lesions. The data also illustrate the value of the mitral valve as a site to assess treatment effects on monocyte/macrophages in vivo. PMID- 2923583 TI - Contraceptive steroid effects on lipids and lipoproteins in cynomolgus monkeys. AB - Seventy-three adult female cynomolgus monkeys fed an atherogenic diet were studied to determine the effect of two different combination contraceptive steroid preparations containing equivalent amounts of estrogen but different progestin components on plasma lipids and lipoproteins. Our hypothesis was that any high density lipoprotein (HDL) lowering effect of the contraceptive steroid preparations was proportional to the rise in total serum cholesterol caused by the progestins. For 2 years, one group (Ovral [Wyeth Laboratories], n = 23) received 75 micrograms norgestrel and 7.5 micrograms ethinyl estradiol daily, while another (Demulen [Searle & Co.], n = 25) received 150 micrograms ethynodiol diacetate and 7.5 micrograms ethinyl estradiol daily. The control group (n = 24) received no treatment. On average, the two oral contraceptive groups had higher total serum cholesterol and triglyceride concentrations but lower HDL cholesterol concentrations and smaller low density lipoproteins (LDL) compared with the control group. There was an inverse relationship between total serum cholesterol and HDL cholesterol for all three groups, but at any given total serum cholesterol concentration between 350 and 500 mg/dl, the Ovral group had HDL cholesterol concentrations that averaged 37% and 14% lower than the control and Demulen groups, respectively. The decrease in HDL concentrations with oral contraceptive treatment was associated with a sharp decrease in (HDL2b)gge protein (82% for Ovral and 59% for Demulen) and a corresponding increase in (HDL3b,c)gge protein as determined by gradient gel electrophoresis. Of 23 animals in the Ovral group, six had HDL subfractions greater than 10 nm diameter (HDL2b)gge compared with 22 of 24 animals in the control group. Although LDL size, on average, was smaller and plasma triglycerides were greater with oral contraceptive treatment compared with controls, there was no apparent relationship between LDL size and plasma triglyceride concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2923584 TI - Electrode placement and mode of recording (differential vs. single-ended) effects on the early auditory-evoked response. AB - The effects of electrode placement and mode of recording (single-ended vs. differential) on latencies and amplitudes of the early auditory-evoked response were studied. The following electrode arrays were evaluated (1) vertex-neck, (2) forehead-ear canal (Enhancer I), and (3) vertex-nape. Responses were obtained on 10 normally hearing subjects at sensation levels (SLs) ranging from 15 to 75 dB. Test-retest reliability was excellent for absolute and interwave latencies for all conditions. The reliability of absolute amplitude was poor, and the stability of the amplitude ratios between waves I and V was even worse. No consistent absolute or interwave latency differences were found among electrode montages. The amplitude data suggest that the forehead-ear canal montage is preferred for differential diagnosis because it enhances the probability of detecting wave I. The electrophysiologic threshold for wave I was 5-10 dB lower with the Enhancer I. However, the vertex-neck and vertex-nape combinations are best for estimating auditory sensitivity because they gave the largest wave V amplitudes and 10-dB lower electrophysiologic thresholds. Although the differential vertex-neck and single-ended vertex-nape recordings yielded comparable results, the single-ended montage employs only two electrodes and the test leads do not require rearrangement when the test ear changes. PMID- 2923585 TI - Detuning of cochlear action potential tuning curves at high sound pressure levels: influence of temporal, spectral and intensity variables. AB - Action potential (AP) tuning curves (TCs), generated by probe stimuli of 60-65 dB SPL with short rise and decay (r&d) times, are less sensitive (have elevated tip thresholds) and are detuned (the frequency is shifted away from that of the probe stimulus, towards a middle frequency of the audiogram). These effects are more pronounced with forward than with simultaneous masking. TCs generated by masking tonal and narrow band noise stimuli are nearly identical, even though the spectrum is much wider for the noise stimulus. Decreasing r&d time has the same effect on TCs generated from both noise and tonal stimuli, even when it only measurably increases the acoustic splatter of the latter. Detuning appears to be related to a temporal-intensity interaction. PMID- 2923586 TI - Interaural interaction in the human auditory cortex. AB - We studied the effect of binaural, contralateral and ipsilateral stimulation on middle- and long-latency auditory-evoked magnetic fields using trains of 40-Hz clicks. The stimuli evoked both a transient response (N100m) and a 40-Hz response, which presumably reflects coalescence of middle-latency responses. Binaural stimuli elicited significantly larger 40-Hz responses and sustained fields than contralateral stimuli. N100m amplitudes did not differ between binaural and contralateral stimulation; the dipole moments were even smaller to binaural than contralateral stimuli. Responses to the ipsilateral stimuli were always the smallest. PMID- 2923587 TI - Phoneme perception via hearing aids with and without compression and the role of temporal resolution. AB - Hearing impairment is more than a sensitivity loss. The causes of reduced discrimination can be found also in deteriorations in loudness perception (recruitment), frequency resolution and temporal resolution. Only recruitment can be compensated for by modern hearing aids, namely by the reduction of the dynamic range by means of compression. However, the introduction of compression introduces temporal distortions, which may deteriorate the temporal cues of speech. In this study the perception of nonsense consonant-vowel-consonant-words presented through hearing aids was studied in a group of 12 hearing-impaired listeners. Phoneme perception in conditions with and without compression was analyzed and related to temporal parameters of the listeners' hearing. A detailed analysis of the patterns of confusions revealed clear qualitative differences in the perception of phonemes with and without compression. These differences can be related to an improved perception of temporal cues like the preburst silent interval of plosives and to spectral changes induced by the activation of the compression circuit. A reduced temporal resolution is disadvantageous for the perception of temporal cues like plosive detection, but our data do not suggest that the perception of temporal cues is hampered excessively by temporal distortions from the compression circuit itself. PMID- 2923588 TI - Simulator sickness in U.S. Navy flight simulators. AB - Flight simulators have become a major factor in pilot training. A general finding from Navy research on simulator design is that equipment features that offer faithful representation improve pilot performance and promote pilot acceptance. To the extent that an aircraft produces motion sickness, its simulator should induce the same result. However, reports of simulator sickness appear to be increasing and a shortcoming in simulation is implied when these effects occur in simulators during maneuvers that do not occasion them in the aircraft. This article presents incidence data from surveys of the 10 simulators at 6 different Naval/Marine Corps Air Stations. Approximately 1,200 simulator flights were recorded. Some severe motion sickness symptoms were recorded and some simulators induced unsteadiness afterwards. Individuals experiencing effects may be at risk if they drive themselves home or return to demanding activities at work. The simulators which exhibited the highest incidences of sickness were helicopter simulators with cathode ray tube (CRT) infinity optics and six-degrees-of-freedom moving base systems. Of those studied, fixed-wing, fixed-base, dome displays had relatively low incidence of simulator sickness. PMID- 2923589 TI - Adaptation to repeated presyncopal lower body negative pressure exposures. AB - Adaptation to chronic stressors, such as exercise and thermal challenges, are well-documented. However, it is not known whether the body can adapt to repeated central hypovolemia. The purpose of this study was to determine if tolerance to presyncopal symptom limited lower body negative pressure (PSL-LBNP; a central hypovolemic stressor), as measured by a cumulative stress index (CSI), was altered by daily PSL-LBNP exposures. On each of nine consecutive days, with a 2-d break between Days 5 and 6, six subjects underwent a PSL-LBNP exposure. By the fifth PSL-LBNP exposure, LBNP tolerance had increased 47%. No further significant improvement was seen after the fifth exposure. While, there was no alteration in mean arterial pressure response during the repeated PSL-LBNP exposures, maximum heart rates were increased significantly over Day 1 after the third daily PSL LBNP exposure. Rate-pressure product was also significantly increased over Day 1 on Days 7 and 8. These findings suggest that adaptation to a simulated hypovolemic stress does occur. Presumably, either the body's compensatory mechanisms become more effective, or there is a resetting of the threshold needed to elicit the presyncopal reactions. PMID- 2923590 TI - Monitoring fluid shifts in humans: application of a new method. AB - Using the "mechanical oscillator technique," the mass density of antecubital venous blood and plasma samples was measured 5-20 times in order to study the influence of postural changes (gravity dependence) on human blood mass density with 0.01 g.L-1 precision, while performing tilt table tests in 17 men. Hemoglobin concentration was measured in 10, and hematocrit in all subjects. Postural fluid shifts were mirrored by accompanying changes in all variables. Blood density (BD) was monitored continuously in five additional experiments from one vein each using two independent densitometers. There were linear relations (p less than 0.01) between all possible combinations of BD, plasma density (PD), blood hemoglobin concentration (Hb), and hematocrit (Ht). Hb can be directly computed from BD (range +/- 10%); the accuracy of Ht determinations from BD increases (range +/- 0.02) if the individual erythrocyte density (ED) and the sample PD are used for calculation. ED was calculated and did not change with body position. ED values of different persons ranged between 1085 g.L-1 and 1095 g.L-1 and did not vary in 15 out of 17 individuals with time (5-75 d). We conclude that ED is closely regulated to an individual set point, that Ht can be computed from BD with higher accuracy if the individual ED and the actual PD values are known, and that BD allows for direct Hb calculation. On-line BD monitoring can be performed with high precision and reveals the individual time course of spontaneous and postural capillary fluid shifts. PMID- 2923591 TI - Heat exchange through cutaneous vasodilation after atropine treatment in a cool environment. AB - This report summarizes a tightly controlled laboratory study in which the thermoregulatory effects of an intramuscular injection of atropine sulfate (2 mg) were compared with a placebo injection of sterile saline during exposure to a cool environment. Four subjects were tested during seated cycle exercise at a moderate exercise intensity (55% Vo2 peak) at an ambient temperature of 22 degrees C (37% relative humidity; ambient water vapor pressure 1.0 kPa). Esophageal temperature (Tes), mean weighted skin temperature (Tsk), and forearm sweating rate (ms) were continuously measured during 30 min of rest and 35 min of exercise. Skin blood flow (FBF) from the forearm was measured twice each minute by venous occlusion plethysmography. Whole-body sweating was calculated from weight changes pre- and post-exercise. The expected decrease in whole-body and local sweating rate (-57% and -68%, respectively) occurred in the atropine treated subjects. By 10-15 min of exercise, dry heat loss (R + C, radiative and convective heat exchange) was significantly elevated from the head, chest, back, arm, forearm, and thigh in the atropine experiments. Core temperature actually decreased 0.2 degrees C (p less than 0.05) in the atropine-treated subjects during exercise as a result of enhanced dry heat exchange. By 25 min of exercise. FBF was 98% (p less than 0.05) greater after atropine treatment. These results show that the peripheral modification of cutaneous blood flow which occurs in atropine-treated subjects is sufficient to markedly alter heat exchange in a cool environment. PMID- 2923592 TI - Behavioral measurement of laser flashblindness in rhesus monkeys. AB - Flashblindness was measured in rhesus monkeys performing a visual detection task. Stimulus field subtense was 3.5 degrees, and mean luminance was 10 cd.m-2. Single pulse laser exposures (doubled Nd:glass, 530-nm wavelength, 20-ns pulsewidth) were presented in Maxwellian-view and formed a 12.5 degrees diameter spot centered on the fovea. The independent variables were: test grating contrast (10% and maximum contrast); test grating spatial frequency (1, 4, 12 c.deg-1); and averaged laser exposure energy (1-94% retinal maximum permissible exposure). The dependent variable was flashblindness, operationally defined as the time between a laser exposure and the first response in a pair of consecutive correct responses (referred to as "time to criterion"). Time to criterion decreased as the contrast of the grating increased. The longest times to criterion were at a spatial frequency of 12 c.deg-1, next longest at 1 c.deg-1, and shortest at 4 c.deg-1. Both the mean and S.E.M. of times to criterion increased with the laser exposure energy. PMID- 2923593 TI - Personal characteristics related to accident histories of Canadian pilots. AB - Over 8,800 returns of a questionnaire, distributed to Canadian pilots, were analyzed. Items were chiefly about life events, hobbies, humour, and characteristics which might bear on susceptibility to "pilot error" accidents. Sets of items were compiled which discriminated whether or not respondents had had an aircraft accident in the past 10 years. Around 70% of the respondents could be classified correctly according to the self-reported accident criterion. Somewhat over half the items were significant accident markers in at least one of four pilot-license categories examined. There was surprisingly little evidence of a "macho" syndrome associated with aircraft accidents; for example, participation in relatively risky hobbies was often negatively related to accident history. This report, like much past research, is entirely retrospective, so that some significant accident markers may only reflect accident aftereffects. Since the questionnaire was not anonymous, however, a follow-up study on the prediction of future accidents is feasible and is being considered. PMID- 2923594 TI - USAF pilot selection and classification systems. AB - A total of 478 pilot candidates were given a computerized test battery, the Basic Attributes Test (BAT) currently being validated for pilot selection and classification. The battery included tests of psychomotor and cognitive/perceptual abilities and personality/attitudinal characteristics. Results indicated that several of the BAT tests were able to improve the prediction of graduation/elimination from flight training and follow-on training recommendation (fighter or non-fighter aircraft) above that provided by currently used paper-and-pencil tests. It was concluded that several of the BAT performance measures were capturing skills and abilities related to flight training performance that are not being assessed by currently used selection instruments. Implications for pilot selection and classification procedures are discussed. PMID- 2923595 TI - A simulator-based approach to training in aeronautical decision making. AB - The effectiveness of a simulator-based approach to training pilot skills in risk assessment and decision making was evaluated in a sample of pilots enrolled in a university aviation science program. The 16 experimental group subjects received 4 hours (h) of classroom instruction designed to enhance pilot judgment skills, followed by 4 simulated cross-country flights during which several critical inflight events occurred. Subjects in the control group received classroom instruction in basic instrument flying, followed by simulator sessions emphasizing instrument flight. Measures of pilot judgment were obtained on all subjects before and after the training, and subjects in the experimental judgment trained group performed significantly better on the posttraining simulation than did control group subjects. The findings suggest that significant gains in pilot decision-making skill can be obtained through the use of the judgment training materials along with simulator practice. PMID- 2923596 TI - Sources of stress affecting pilot judgment. AB - The initial stages of our research on the effects of the overassessment or underassessment of the consequences of nonroutine events (a potentially important factor in decision-making by pilots) is described. Critical difficulties in the measurement of life stress are discussed and a partial solution is suggested in the form of the Life Events Questionnaire (LEQ), an instrument on which individuals report the nature of stressful events, when they happened, and how much they concern them at the time of testing. The results show that the tendency to overassess or underassess the consequences of nonroutine events is consistent within individuals, but is unaffected by life stress levels on the artificial air traffic control simulation used. Analysis of LEQ results showed that high stress subjects had much higher chronic than acute stress scores (p less than 0.001), although the chronic and acute scores were virtually identical for low stress subjects. PMID- 2923597 TI - Communication indices of crew coordination. AB - The relationship between communication patterns and performance in 10 two-person flightcrews is explored with the aim of identifying speech variations which differentiate low- and high-error full mission simulator flights. Verbal data, transcribed from the videotaped performances, are treated as interactive sequences of speech events in which statements spoken by one crewmember are considered within the context of the other crewmember's prior and subsequent speech. Specific speech patterns characterized each crew, but the overriding findings included: a) marked homogeneity of patterns characterizing low-error crews, interpreted as the adoption of a standard form of communicating, and b) heterogeneity of patterns characterizing high-error crews, interpreted as the relative absence of a conventionalized form. Because conventions are regularities which confirm the expectations of those involved, predictability of crewmember behavior should be greater when standard conventions are followed. We conclude that such a practice can facilitate the coordination process and enhance crew performance. PMID- 2923598 TI - Vasodepressor syncope induced by lower body negative pressure: possible relevance to +Gz-stress training--a case report. AB - We present a case report of vasodepressor syncope with brief sinus pause in a 26 year-old male subject following a graded lower body negative pressure (LBNP) challenge culminating at -70 mm Hg. Cessation of the LBNP protocol resulted in the return of heart rate and blood pressure activity to pre-challenge levels. Sinus arrest during central hypovolemic stress has been noted in the literature. Its potential in rare cases during exposure to high levels of LBNP should be noted as increasing numbers of investigators utilize presyncopal LBNP testing to assess the orthostatic responses of pilots and astronauts. PMID- 2923599 TI - The giant hand phenomenon. AB - The "giant hand" is a form of recognized spatial disorientation. An experienced fighter pilot described the events leading up to ejection from his out-of-control aircraft. Investigation of the mishap found no flight control problems and attributed the accident to the giant hand phenomenon. A survey of tactical aircrews indicated that this form of spatial disorientation is not an unusual occurrence. Past training of aircrew to deal with this problem has been inadequate. Earlier reports of this phenomenon recommended attempting to recover the aircraft by grasping the stick using only the thumb and index finger rather than the entire hand. Further investigation to include simulation of this phenomenon in advanced spatial disorientation trainers should contribute to aviation safety. PMID- 2923600 TI - Chemical hazards in aeromedical aircraft. AB - Several potentially hazardous chemicals are required to make modern military aircraft fly. With each airevac mission, the possibility exists for structural failure of a fluid system, resulting in contamination to flight/medical crews, patients, and passengers. Aeromedical Evacuation Crewmembers (AECMs) need to be aware of the hazardous chemicals used in aircraft and areas where there is an increased risk to those in and around the aircraft. This study identified potential areas for chemical leakage, such as refuel receptacles, hydraulic reservoirs, hydraulic motors, doors, ramps, engines, and more. Further, it identified the basic first aid procedures to perform on people contaminated with jet fuel, hydraulic fluid, engine oil, fire extinguisher agents, LOX and other fluids. First aid procedures are basic and can be performed with supplies and equipment on a routine aeromedical evacuation mission, AECMs trained in a basic awareness of hazardous aircraft chemicals will result in crews better prepared to cope with the unique risks of transporting patients in a complicated military aircraft. PMID- 2923601 TI - Deploying and testing an expandable surgical chamber in microgravity. AB - Prolonged spaceflights will increase the possibility of injury to flight crews and mission personnel. These injuries are anticipated to include foreign body injury, mechanical injury, and burns. Surgical repair of these injuries must take into consideration problems of contamination of the injury as well as contamination of the Space Station or transport vehicle environment. Use of a portable expandable surgical chamber is felt to be the most efficient and effective means of providing necessary surgical care in a Space Station environment. A first prototype expandable surgical chamber has been developed and tested in zero gravity. A second prototype has now been developed and will be tested. PMID- 2923602 TI - Cases from the aerospace medicine residents' teaching file. Case #29. Evaluation and management of an aviator. PMID- 2923603 TI - Rest- and stimulation-dependent changes in exchangeable calcium content in rabbit ventricular myocardium. AB - Ca2+ shifts in the isolated, perfused ventricular muscle of rabbit hearts were investigated with the aid of 45Ca under the conditions of complete equilibration of preparations with 45Ca containing solution. The "cellular" 45Ca content was calculated by subtraction of 45Ca2+ dissolved in the free water of extracellular space from the total tissue 45Ca2+ content. The "cellular" content of 45Ca in stimulated (60 per min) preparation was 0.887 +/- 0.067 mmol/kg wet weight (w.w.). Six minutes of rest resulted in the drop of this content to 0.503 +/- 0.054 mmol/kg w.w. despite continued perfusion with 45Ca containing solution. Contractile force (CF) decreased at that time to 23% of control. The first post rest contraction (RSC) resulted in a gain of 0.073 mmol45Ca/kg w.w. Both the content of 45Ca and CF returned to the pre-rest values when stimulation was resumed. The difference between the 45Ca content of post-rest stimulated and rested preparations (0.384 mmol/kg w.w.) is equivalent to Ca2 fraction (Ca2), previously described in guinea pig ventricular myocardium (17, 12). However, the volume of rabbit Ca2 is only about 42% of that in guinea pig. Caffeine in concentration 12.5 mM, which did not displace Ca2 from guinea pig ventricular muscle, decreased Ca2 in the rabbit ventricle by 44%. CCCP, a protonofore destroying the mitochondrial protone gradient essential for Ca2+ uptake and maintainability, displaced Ca2 completely from rabbit ventricles. These results, although far from conclusive, do suggest that both the mitochondria and sarcoplasmic reticulum might be the site of the rate-dependent Ca2 fraction. The physiological meaning of differences in Ca2 content between rabbit, guinea pig, and rat ventricular myocardium is discussed. PMID- 2923604 TI - GTP-independent stimulation of rabbit heart adenylate cyclase by isoproterenol at physiological ATP concentrations. AB - Isoproterenol increased the activity of the adenylate cyclase of rabbit heart sarcolemmal membranes in the absence of added GTP. ATP, the ATP-regenerating system, and the sarcolemmal membrane preparation were eliminated as possible sources of contaminating GTP. Isoproterenol-stimulation increased as ATP was raised. At 0.5 mM ATP, isoproterenol increased activity by 19% whereas at 5 mM ATP isoproterenol increased activity by 121%. There was no change in basal activity between 0.5 and 5 mM ATP. Stimulation by Gpp(NH)p and NaF increased slightly between 0.5 and 5 mM ATP; stimulation by KCl was unaffected. GTP does not activate cyclase d. GTP does not activate cyclase to the same extent as Gpp(NH)p even though the two act at the same site on Ns (the stimulatory guanine nucleotide-binding protein). GTP decreased cyclase activation by Gpp(NH)p in a concentration-dependent fashion when the two were added to the assay simultaneously. Increasing ATP from 0.5 to 5 mM did not reduce activation by Gpp(NH)p when both were added simultaneously to the assay. This suggests that ATP does not interact with the same site as Gpp(NH)p. ATP gamma S, an analogue of ATP which irreversibly thiophosphorylates proteins, did not irreversibly support activation by isoproterenol. The effect of ATP in supporting isoproterenol stimulation is not, therefore, thought to be due to phosphorylation of a protein. PMID- 2923605 TI - Coronary collateral reserve during exercise induced ischemia in swine. AB - We determined coronary collateral vasodilator reserve during exercise-induced ischemia in 17 mini-swine. We induced coronary collateral development in the left circumflex bed by placing an ameroid occluder on that artery. Four weeks later we studied the animals at rest and during exercise (EX) eliciting heart rates (HR) of 240 and 265 beats/min. We measured myocardial blood flow with microspheres and myocardial function by wall thickness sonomicrometry gauges. At matched exercise HRs we treated the animals with nifedipine (10 micrograms/kg IV) (EXN 10), nifedipine (100 micrograms/kg IV), (EXN 100), and adenosine infusion (1.2 mg/min/kg) EXAD. EXN 10 did not significantly alter hemodynamics compared to EX but EXN 100 and EXAD both decreased blood pressure significantly (p less than 0.05). Ischemic endocardial/nonischemic endocardial flow ratios and collateral resistance served as indices of vasodilator reserve. In the ischemic zone exercise reduced vasodilator reserve to 24 +/- 3% in the endocardium and 64 +/- 7% in the epicardium. Neither EXN 10 nor EXAD improved exercise-induced ischemia measured either as flow or function. However EXN 100 improved function during exercise-induced ischemia without improving coronary collateral flow. We conclude there is no additional coronary flow reserve during exercise-induced ischemia in the collateral dependent bed of the pig a few days after occlusion that can be recruited. Large doses of nifedipine improve function by direct action on the myocardium or by reducing afterload. The lack of development and deep myocardial distribution of the coronary collateral vessels in the pig may be an important factor of why these nifedipine responses differ from those reported in species which have primarily large epicardial coronary collaterals. PMID- 2923606 TI - Halothane anesthesia reduces inducibility of ventricular tachyarrhythmias in chronic canine myocardial infarction. AB - This study examined the effects of 2% halothane general anesthesia on ventricular electrophysiological properties and inducibility of sustained ventricular tachycardia (VT) and ventricular fibrillation (VF). Dogs with chronic anterior infarction and control dogs (no infarction) were studied before and after anesthesia using chronically implanted ventricular epicardial electrodes. PQ interval was increased by 15% with halothane, but QRS duration, QT interval, QTc, and sinus rhythm cycle length were unaffected by anesthesia. Diastolic threshold was unchanged by halothane. Halothane caused significant increases of 10-30% in ventricular effective refractory period (ERP) both in control and in infarct animals. VT and VF were not inducible in any of the nine control animals either before or after anesthesia. In infarct animals 34 of 75 (45%) had inducible VT or VF prior to halothane, but the incidence of inducible arrhythmias was significantly lower at 29% (22 of 75 animals) after halothane (p less than 0.01). In 75% of animals in which halothane suppressed inducibility of tachyarrhythmias, halothane-induced increases in ERP prevented achievement of the short extrastimulus coupling intervals at which the arrhythmias were induced before anesthesia. IN CONCLUSION: halothane anesthesia reduces the incidence of inducible sustained ventricular tachyarrhythmias in chronic canine myocardial infarction. PMID- 2923607 TI - Electrophysiological interactions between carbachol and class I antiarrhythmic drugs (lidocaine, quinidine)--experimental studies in rabbit atrial myocardium. AB - Cholinergic agents exert no direct effect on the fast Na+ inward current but may influence the binding characteristic of class I antiarrhythmic drugs in atrial myocardium by shortening the action potential (AP) duration or by increasing the resting potential (RP). In order to examine such possible interactions we performed experiments using conventional intracellular microelectrodes on isolated preparations of rabbit atrial myocardium (Ke 2.7 mM, temperature 32 degrees C). At first the influence of the cholinergic agent carbachol (1 mg/l = 6.7 x 10(-6) M) on the RP and AP was examined at different stimulation rates (1.0, 2.5, and 3.3 Hz). Thereafter measurements were repeated under the influence of lidocaine (10 mg/l = 2.2 x 10(-5) M) or quinidine (5 mg/l = 2.2 x 10(-5) M) alone and in combination with carbachol (1 mg/l). RESULTS: (statistically significant differences, p less than 0.05): Carbachol increased the RP by about 10 mV and shortened the AP by about 60%. The maximal upstroke velocity of the AP (Vmax) was not significantly altered at 1.0 and 2.5 Hz, but increased under carbachol at 3.3 Hz. After addition of carbachol to the lidocaine-containing solution, Vmax increased to its control level at all stimulation rates. In experiments with quinidine, Vmax also increased after addition of carbachol but remained significantly below the control values. CONCLUSIONS: Carbachol effects on Vmax are most likely attributable to earlier recovery (caused by the shortening of the AP) and to faster recovery kinetics (due to hyperpolarization). The attenuation of the class I effect of lidocaine by carbachol can thus be considered mainly a consequence of the shortening of the inactivated state which results in a reduced affinity of lidocaine to its receptor and allows earlier dissociation of the drug. Minor binding of the drug due to hyperpolarization may play the major role in interactions between carbachol and quinidine. PMID- 2923608 TI - Enhanced myocardial preservation by nicotinic acid, an antilipolytic compound: mechanism of action. AB - The cardioprotective effects of an antilipolytic compound, nicotinic acid, on arrested-reperfused myocardium were investigated in the isolated in situ pig heart preparation. Hearts were preperfused for 15 min in the presence of (5-3H) glucose and (U-14C)-palmitic acid. Half of the hearts were then perfused with 0.08 mM nicotinic acid for an additional 15-min period, while the remaining control hearts received unmodified perfusion. Arrest was then induced in all animals for 2 h using hypothermic K+ cardioplegia, followed by 60 min of normothermic reperfusion. In control hearts, there were significantly greater levels of long-chain acyl Co-A and acyl carnitine and lower levels of membrane phospholipids than in the nicotinic acid group. While nicotinic acid inhibited beta-oxidation during pre-ischemia and reperfusion, it also prevented the degradation of membrane phospholipids. The net result was a reduction of free fatty acid accumulation during arrest and reperfusion in the nicotinic acid group. Glycolysis, as reflected in 3H2O production, was significantly increased by nicotinic acid administration. In the control heart as compared to the nicotinic acid group, the incorporation of 14C-label from palmitate into triglyceride and cholesterol during arrest was enhanced, while incorporation into phospholipids was depressed. The cardioprotective effects of nicotinic acid were demonstrated by decreased release of creatine kinase and improved coronary blood flow, and cardiac contractility in the reperfused myocardium supplemented with nicotinic acid compared to the control group. These results suggest that nicotinic acid significantly protects the arrested-reperfused myocardium by a) preventing elevation of myocardial fatty acid levels, b) stimulating glycolysis by limiting fatty acid oxidation, c) inhibiting degradation of membrane phospholipids, and d) preventing accumulation of fatty acid metabolites with harmful detergent properties. PMID- 2923609 TI - High-energy phosphates, myocardial contractile function and material properties after short periods of oxygen deficiency. AB - To investigate myocardial performance and diastolic properties after repeated periods of oxygen deficiency auxotonic and isovolumic measurements were performed after three periods (4 min) of asphyxia in Wistar rats (n = 19). Additionally, the response of the peak isovolumic left ventricular pressure to postextrasystolic potentiation was measured. The hemodynamic results were compared to the levels of high-energy phosphates. Already after 15 min of recovery from asphyxia auxotonic measures of systolic function were completely normal compared to the control group (n = 19). Isovolumic measurements after 20 min of postasphyctic recovery, however, demonstrated a considerable reduction of the peak left ventricular pressure (226.5 +/- 7.5 mm Hg vs. 262.6 +/- 3.4 mm Hg in controls, mean +/- SEM (p less than 0.01) indicating persistence of decreased postischemic contractile performance. The relative effect of postextrasystolic potentiation was similar in both groups, but could not compensate for the reduced performance of the postasphyctic hearts: the absolute postextrasystolic peak isovolumic pressure of the postasphyctic hearts was lower than the value of the regular isovolumic peak pressure in the controls. Diastolic properties (pressure/volume and stress/strain relationships) of the postasphyctic myocardium remained unchanged. The total sum of the adenine-nucleotides decreased from 7.2 +/- 0.2 to 5.6 +/- 0.3 mumol/gww (p less than 0.01). ATP was reduced from 4.8 +/- 0.2 to 3.9 +/- 0.3 mumol/gww (p less than 0.01). Phosphocreatine was elevated to 7.0 +/- 0.6 mumol/gww, x +/- SEM (p less than 0.01). Our results demonstrated normal postasphyctic basal hemodynamics and material properties. Thus, the energy supply was sufficient to maintain steady state conditions - in spite of decreased overall adenine-nucleotide levels. Isovolumic measurements and postextrasystolic potentation tests, however, indicated that the contractile performance of the postischemic myocardium was still reduced. This functional limitation cannot be explained by altered material properties and is probably not causally related to the decreased overall ATP content. PMID- 2923610 TI - Individualizing the Good Behavior Game across type and frequency of behavior with emotionally disturbed adolescents. AB - The effects of the Good Behavior Game (GBG) individualized across type and frequency of behavior were examined in three classes of severely behaviorally disordered students using a reversal design. The findings showed that the individualized GBG was effective in simultaneously decreasing a variety of inappropriate behaviors exhibited by the three classes, including inappropriate verbalizations, touching, negative comments, cursing, and drumming. Teacher and student satisfaction data indicated that both groups had positive reactions to the individualized GBG. Reasons for the success of the technique are discussed. PMID- 2923611 TI - A peer-mediated intervention with clinic-referred socially isolated girls. Generalization, maintenance, and social validation. AB - Peer-mediated interventions have been widely employed with seriously impaired autistic and handicapped children to modify social withdrawal. This study extends the literature by examining the impact of a peer intervention on the interactions of developmentally normal, socially isolated girls. Two to three actual classroom peers were trained to serve as helpers to initiate and maintain interactions with the subjects. The intervention was introduced sequentially across 2 girls in a multiple-baseline design, and a within-subject ABA withdrawal design was used to assess maintenance. Behavioral observations during recess periods indicated that both children's positive social interactions with peer helpers and other classmates were increased significantly during intervention and were maintained in return-to-baseline conditions and at 4-month follow-up. Increases in positive social interactions of both subjects generalized to a second recess setting, in which intervention was not introduced. Subjects' interactions in both recess settings reached levels comparable to those of social-comparison groups of peers. Teacher and self-report ratings suggested that both girls had fewer social problems and experienced less loneliness and dysphoria as a result of the intervention. PMID- 2923612 TI - Group conversational-skills training with inpatient children and adolescents. Social validation, generalization, and maintenance. AB - Two groups of inpatient youths (n = 4 and n = 5) received group conversational skills training. Conversational component behaviors of both groups at baseline were compared to the behaviors of normal youth from the community. For each inpatient group, component behaviors on which they were most discrepant from normal youths were selected for training. Multiple-baseline designs across component behaviors were used and patients were trained to socially-validated criterion levels. Effectiveness of training was demonstrated through (a) behavioral ratings during dyadic, unstructured conversations with other members of their group, (b) behavioral ratings during conversations with unfamiliar nonpsychiatric persons, (c) global ratings of conversational effectiveness by nonpatient peers, (d) generalization to in vivo conversations, and (e) maintenance of improvement at 1- and 3-month follow-up assessments. Results were replicated across both groups and indicated that training effects were socially validated, generalized to conversations with unfamiliar persons and to in vivo conversations, and maintained over time. PMID- 2923613 TI - From cars to carts. Increasing safety belt usage in shopping carts. AB - A modified reversal/multiple-baseline design across three supermarkets was used to examine the effectiveness of behavioral interventions in increasing the frequency of safety belt usage in shopping carts. Following low baseline rates, safety belt usage increased significantly during a prompt-plus-personal-contact condition at Stores 1 and 2. Safety belt usage then decreased, but remained above baseline levels, in a prompt-alone condition at both stores. However, at Store 1, usage increased when the personal-contact procedure was reintroduced but reversed to lower levels in a second prompt-alone condition. Finally, social validity scales indicated that adult shoppers with children favored both safety belts on carts and the experimental procedures used in this study and said that they intended to use safety belts on carts in the future. Implications and directions for further research are briefly discussed. PMID- 2923614 TI - Contingent glove wearing for the treatment of self-excoriating behavior in a sensory-impaired adolescent. AB - Contingently applied protective equipment is a treatment strategy to control self injury but one that has received limited experimental evaluation. This study examined the effects of contingent glove wearing for the treatment of self excoriating, skin picking behavior in a sensory-impaired adolescent. Brief application of gloves following occurrences of self-injury produced clinically significant reductions in the behavior as demonstrated in a multiple-baseline design. Intervention effects were maintained at 1- and 3-month follow-up assessments. PMID- 2923615 TI - Effects of undesirable, competing behaviors on the generalization of adaptive skills. A case study. AB - This study provides a systematic demonstration of generalization failures in which irrelevant stimulus control of competing responses interferes with, or overrides, the stimulus control of adaptive behavior developed during training. Appropriate and inappropriate verbal responses by a 26-year-old woman with severe mental retardation served as the dependent variables. A reversal design across trained and nontrained settings indicates that presenting a stimulus with a prior history of control over "inappropriate" verbalizations concurrently with a stimulus controlling newly acquired "appropriate" verbalizations significantly reduces the strength of the appropriate stimulus-control relationship. The implications for training generalized skills are discussed. PMID- 2923616 TI - Aversive conditioning of visual screening with aromatic ammonia for treating aggressive and disruptive behavior in a developmentally disabled child. AB - This study investigated the usefulness of aversive conditioning of a mild punishment procedure that had ceased to suppress target behaviors to clinically acceptable levels. A 6.8-year-old severely retarded boy with high levels of aggressive, destructive, and loud screeching behaviors was readmitted to a psychiatric facility to adjust behavioral programs and rule out seizure disorder. A design combining withdrawal and multiple baselines across behaviors tested for effects of aversive conditioning of visual screening with ammonia and the impact of anticonvulsant medication (carbamazepine, phenytoin). Data indicated that aversively conditioned visual screening temporarily lowered rates of responding. It is tentatively concluded that aversive conditioning might be a useful mechanism to strengthen suppressive effects of mild punishment procedures and a promising approach for alleviating placement problems due to maladaptive behaviors in mentally retarded persons. Maintenance of treatment effects, community placement, and the mandate to choose the least restrictive aversive treatment alternative are discussed. Anticonvulsant medication showed no beneficial effect for the target behaviors investigated. PMID- 2923617 TI - [Individual glycoside therapy using serum concentration determination in heart insufficiency of horses]. AB - 23 horses and one donkey with congestive heart failure are treated with a standardized methyldigoxin dose (0.0032 mg/kg of body weight). The therapy is controlled by the serum concentration of the cardiac glycoside. 4 horses have a higher and 13 horses a lower serum concentration as necessary for therapeutic approach. The influence of additional diseases and medications is demonstrated. Finally a rule for the evaluation of the individual therapeutic glycoside-dose is given. PMID- 2923618 TI - [A hemagglutination inhibition test for control of the quality and effectiveness of highly-purified C. chauvoei toxoid vaccine]. AB - To control quality and efficiency of a highly purified C. chauvoei vaccine which has been developed in Gottingen a haemagglutination-inhibition test is presented. Laboratory and field trials did demonstrate the value of the test. Vaccinated guinea pigs which presented positive HIT titers survived the challenge. Cattle, vaccinated with the vaccine in Germany, Madagascar and Mexico showed positive titers which could be boostered through repeated vaccination. PMID- 2923619 TI - [Experiences with vaccination against Haemophilus pleuropneumonia of swine]. AB - In a Haemophilus pleuropneumonia problem herd with piglet production and fattening, sows and weaned pigs were vaccinated with a Danish vaccine (Pleurinord). Due to consequent vaccination of the sows the health of the piglets could be improved decisively, resulting in an increased number of raised piglets per sow and year from 16.8 to 20.3. In the vaccinated fattening pigs compared to the unvaccinated ones the following effects were observed: markedly reduced expenses for medication and a markedly reduced frequency of characteristic lesions in the respiratory tract; the improvement of the daily weight gains and the reduction of losses remained behind the expectations. Decisive causes for this were respiratory and enteric diseases unrelated to Haemophilus, which were favoured by serious mismanagement and inadequacies in the feeding regimen and barn climate. On the example of the vaccinated herd it is shown how important the analysis of a multifactorial disease situation is, in order to be able to objectify better or at all the influence of a vaccination program under field conditions. Within a concept of prevention and control of Haemophilus pleuropneumonia the vaccination is a helpful part. PMID- 2923620 TI - Role of cardiolipin in the functioning of mitochondrial L-glycerol-3-phosphate dehydrogenase. AB - Adriamycin was used in situ, in isolated liver mitochondria of hyperthyroid rats to study the role of cardiolipin in the functioning of FAD-linked L-glycerol-3 phosphate dehydrogenase. The apparent kinetic parameters of the reaction catalyzed by the enzyme were affected by adriamycin. The effect of adriamycin was dependent on the electron acceptor, suggesting the existence of distinct binding sites for hydrophobic and hydrophilic acceptors. Assuming a correlation between the two plateaus observed upon binding of adriamycin to the mitochondria and the penetration of the drug into the two leaflets of the inner membrane [Cheneval et al. (1985) J. Biol. Chem. 260, 13003-13007], we can deduce that cardiolipin in both leaflets influences predominantly the electron acceptor binding site(s). PMID- 2923621 TI - The cDNA-derived amino acid sequence of chick heat shock protein Mr 90,000 (HSP 90) reveals a "DNA like" structure: potential site of interaction with steroid receptors. AB - We report cDNA sequence, the complete derived aa sequence, and a predicted secondary structure of the chick hsp 90, a protein which has been found to form complexes with steroid hormone receptors. The modelling of the most negatively charged "region A" indicates that the alpha-helices of this portion of hsp 90 mimick DNA configuration. We propose that this region can, in absence of hormone, interact with and cap the positively charged DNA-binding domain of steroid receptors. PMID- 2923622 TI - Cloning and sequencing of the cDNA for human monocyte chemotactic and activating factor (MCAF). AB - cDNA clones having a nucleotide sequence encoding a human monocyte chemotactic and activating factor (MCAF) were isolated and sequenced. The amino acid sequence deduced from the nucleotide sequence reveals the primary structure of the MCAF precursor to be composed of a putative signal peptide sequence of 23 amino acid residues and a mature MCAF sequence of 76 amino acid residues. The amino acid sequence of MCAF showed 25-55% homology with other members of an inducible cytokine family, including macrophage inflammatory protein and some putative polypeptide mediators known as JE, LD78, RANTES and TCA-3. This suggests that MCAF is a member of family of factors involved in immune and inflammatory responses. PMID- 2923623 TI - Differential calmodulin gene expression in fetal, adult, and neoplastic tissues of rodents. AB - Differential expression during rat development of three genes for calmodulin (CaM I-III) was examined in amnion, decidua, embryo, liver, placenta, parietal and visceral yolk sacs and uterus. CaMI expression was constant except for increasing activity in VYS during gestation. CaMII expression increased in all tissues except for a decrease in embryo. CaMIII did not change dramatically. Differential expression was also found in chemically or virally induced rat tumors, and in metastatic lung nodules of mouse mammary carcinoma. CaMII was the major gene expressed in all these neoplastic tissues. PMID- 2923624 TI - Inhibition of osteoclastic acid phosphatase abolishes bone resorption. AB - Osteoclastic acid phosphatase is a member of a widely-distributed class of iron containing proteins with acid phosphatase activity. Antibodies raised against one member of this class cross-react with other members from the same or different species, but not with acid phosphatase isoenzymes of different types. When antibodies to one such protein, porcine uteroferrin, are added to medium in which rat osteoclasts are incubated on devitalised cortical bone, both bone resorption and acid phosphatase activity are markedly inhibited. Furthermore, addition of molybdate (an inhibitor of this class of acid phosphatases) also inhibits both bone resorption and enzyme activity. These observations strongly suggest a functional role for osteoclastic acid phosphatase in bone resorption. PMID- 2923625 TI - Substoichiometric concentrations of ATP-G-actin are required to anneal actin polymerized by calcium ions. AB - At 3 degrees C and pH 7.0, the addition of 40 nM ATP-G-actin to F-actin (12 microM as the monomer), polymerized in the presence of 4 mM CaCl2, determines a substantial and rapid increase of the viscosity of the solution, which is accompanied by the incorporation of the ATP-G-actin added into the polymer. The hypothesis that the presence of ATP-actin at the filament end(s) promotes the annealing reaction is substantiated by the finding that, after the addition of ATP-G-actin, the average filament length is increased. This finding is relevant, not only because it provides evidences in favour of the existence of annealing but also because it shows that the concentration of ATP-G-actin influences the filaments length distribution through a mechanism different from the elongation reaction. PMID- 2923626 TI - Use caution when extrapolating from a small sample size to the general population. PMID- 2923627 TI - Minority workers: educational models for workers, health providers, and planners. AB - 1. The Labor Occupational Health Program's (LOHP) experience with occupational health problems in minority communities demonstrates that information on a client's past work history and occupational exposures is essential in providing comprehensive health care. Occupational health histories are an excellent tool to utilize in community health. 2. Community clinics and primary health care professionals are integral components in health care delivery services. 3. The occupational health professional has a unique opportunity to provide leadership in educating community health providers about the basics of occupational health. PMID- 2923628 TI - Chronic lead exposure: a problem for minority workers. AB - 1. Despite regulatory and case identification efforts, lead exposure continues to pose a major health problem for minority workers. 2. Minority workers are overrepresented in lead industries such as lead smelting, lead storage batteries, lead pigment production and pottery. 3. Preliminary data from recently instituted lead registries in California and Texas suggest that minority workers continue to be overexposed to lead. 4. A federal policy that strengthens enforcement of the OSHA lead standard is needed to reduce lead exposure among minority workers. PMID- 2923630 TI - Containing health care costs: the occupational health nurse as case manager. PMID- 2923629 TI - AIDS and the minority health care worker. AB - 1. Large groups of health care workers, many of whom are among ethnic minorities with potential for occupational exposure to HIV/HBV, are generally underserved in training on prevention of occupational transmission of the viruses. 2. The inadequacy of training for indirect client care personnel appears to be one of the primary reasons for high rates of needlestick injuries and exposure to blood. 3. Training in appropriate infection control techniques can help reduce the uneasiness and fear among health care workers over occupationally-related HIV/HBV transmission. PMID- 2923631 TI - Responding to the patient who has AIDS. AB - Acquired immune deficiency syndrome (AIDS) has burrowed its way into the fabric of American society. Unless we recognize the extensive and permanent damage it can do there, we are going to lose more than human lives. The tradition of medicine is that physicians do not abandon the sick, whoever they are and whatever they have done, and overall Americans can be proud of the way we have successfully faced the challenge of fairness. Now, however, we need to focus on the "professional will to respond." Doing so means providing support to the individual physician, ensuring that everyone in the profession is informed about AIDS and makes all necessary adjustments of behavior and commitment. The medical profession must lead the public and other health professionals in responding morally, ethically, personally, and professionally to the AIDS epidemic. Otherwise, physicians will be relegated to the sidelines as the electorate, courts, and government agencies debate and adjudicate AIDS issues. PMID- 2923632 TI - A matter of integrity. AB - There may be more aberrations in the moral and ethical behavior of scientists and physicians now than in the past. Fraud and misconduct in research have become a major stress point for both science and medicine. The "premed syndrome" (cheating in medical school and dishonesty during residency training) and fraud in medical practice are well known. Further, studies show that medical students are lenient towards dishonesty in education and practice. One result is that researchers and faculty members may turn to fraud when faced with the pressures to excel, produce, publish, be promoted, and win tenure. Also, physicians' ties to research and commercial endeavors raise questions of conflict of interest that may tarnish the medical image and compromise research findings. An AAMC ad hoc committee on research fraud identified three steps institutions might take: determination of the magnitude of the problem by a formal study; institution of guidelines for research, publication, and promotion; and establishment of policies for investigating allegations of fraud. Because of the problems of dishonesty, fraud, and conflict of interest, academic medical institutions must establish codes of conduct to govern professional life. PMID- 2923633 TI - Health services research: is it good for you and me? AB - Two principles shape an applied research field such as health services research. First, studies can be classified as methodological, descriptive, analytical, or experimental; and second, health services research is conducted at two levels, the doctor-patient level and the policy level. Twenty years of increasingly sophisticated description and analysis allow researchers now to measure better the appropriateness and outcome of care, both at the policy level (do cuts in medical coverage affect patients' health?) and at the individual level (does physicians' behavior affect patient compliance and thereby outcome?). Further, researchers have been able to develop increasingly useful measures of patient health status and function. Consequently, relations between the public and physicians and medical institutions will change further as patients receive more and better information about hospital mortality rates, quality-of-life measures, and similar results of health services research. Conducting good health services research is complicated, depends upon teams of physicians and social scientists working together, and produces complex, not simple, results, but it is worth the effort because the results make a difference to physicians and to the American people. PMID- 2923634 TI - U.S. outlook issues: putting America's house in order. AB - Despite the economic growth in 1987 and 1988, there are three issues of concern: the strength of consumer spending, the risk of accelerating inflation, and the federal budget deficit. The history of recent consumer spending is reviewed, and the recommendation made that if the recent "binge" of 1987-1988 has caused the economy to overshoot its production capacity, monetary and fiscal policies should be adjusted to rein in the spending. Regarding inflation, despite projected productivity gains, the economy seems to be heading for a 4.5%-5.0% core rate of inflation, a rate that can surge to 1970s-like levels with any substantial bad news. The observation is made that no major sustained cut in financing costs will occur until U.S. fiscal policy is changed. Regarding the deficit, voters cannot seek more services without either higher taxes or higher interest rates; growth alone will not cure the federal deficit. The distinction between good and bad types of debt is made and the history and causes of the $ 2 trillion increase in federal debt between fiscal years 1980 and 1988 is reviewed. Corporate debt and the recent corporate acquisitions and leveraged buyouts are analyzed. Public policy considerations arise primarily from the need to limit the system risks imposed by the scale of the buyout mania and to insure fair treatment of current debt holders of target corporations. Greater regulation of pension investments may be necessary, and widespread use of change-of-ownership clauses in bonds would be productive. PMID- 2923635 TI - Ethics in patient referrals. PMID- 2923636 TI - Minorities and health. PMID- 2923637 TI - Classifying the content of board certification examinations. AB - A system of medical classification based on the fundamental dimensions of body system, etiology, and stage of disease was evaluated by classifying the content of one specialty board's examinations. Ten physicians encoded 2,310 test items that constituted three previously administered certification-recertification examinations of the American Board of Family Practice. Analysis of the data for the major content of one of these certification examinations suggests that a profile based on this classification system might provide a specialty board, the residency programs, and candidates for certification with important information not produced by discipline labels or disease names. This classification system may allow a board to define more effectively the content of its examinations, monitor other requirements for certification, and communicate its standards to the medical profession and society. PMID- 2923638 TI - Evaluation of clinical instructors by third-year medical students. AB - Third-year medical students used 12 descriptive items to evaluate the teaching skills of first-year residents, senior medical residents, preceptors (internal medicine fellows), and attending physicians. Intraclass correlations showed that the students were able to judge their instructors reliably. Further analyses were then carried out to determine whether students differentially evaluated the four instructor groups. Three of the descriptive items that related to overall evaluations, as well as the mean rating of all items, indicated no group differences. However, when the groups were compared on specific teaching characteristics (by means of a multiple-group discriminant function analysis), systematic differences were found. The first function differentiated the groups in terms of the cognitive and experiential characteristics of the instructors, with attending physicians being rated the highest and first-year residents the lowest. In contrast, the third function separated the groups in terms of interpersonal skills; on this function, the senior medical residents were rated the highest and preceptors the lowest. It is concluded that students make sophisticated judgments in evaluating their clinical teachers. PMID- 2923639 TI - Predicting the medical school progress of minority students who participated in a preparatory program. AB - The grade-point averages (GPAs), Medical College Admission Test (MCAT) scores, and Student Progress Committee (SPC) ratings of 75 minority students who had attended a preparatory program at Southern Illinois University School of Medicine at some period from 1976 through 1986 were analyzed to determine how these variables related to the retention and progress of these students in medical school. Although those retained had higher SPC ratings than those not retained, stepwise regression revealed that none of the variables predicted retention. The MCAT Reading score, however, was significantly higher for students who progressed on schedule; it was the only significant predictor of progress. PMID- 2923640 TI - Course selections and career plans of black participants in a summer intervention program for minority students. AB - From 1985 through 1987, data were gathered on 151 participants in a summer program at the Bowman Gray School of Medicine of Wake Forest University. This program was designed for academically talented minority students to promote their awareness of medicine as a potential career and to strengthen their science and mathematics backgrounds. Among the findings were that the differences in the students' selections of courses in their schools were small, regardless of the occupational or educational levels of their parents, and that the gender of the students had little relation to their choices of advanced mathematics and science courses. The significance of the findings is discussed and the importance of continued support of such intervention programs is emphasized. PMID- 2923641 TI - An experiment involving reading assignments in a medicine clerkship. AB - Sixty-one students from two medicine rotations were assigned randomly to experimental and control groups. Instruction was the same for both except that the control group was assigned required readings while the experimental group was instructed to find and read information relating directly to their patients' conditions. The groups were compared in terms of their performances on a final written examination, on the National Board of Medical Examiners Part II examination (NBME II), and on the Medicine Subtest of the NBME II, and also in terms of the effects of prior clinical rotations on their examination scores. Although no statistically significant differences were found, other findings suggest that several areas of clinical instruction warrant further investigation. PMID- 2923642 TI - Teaching first-year students the interpersonal recall process for patient interviews. AB - The authors investigated how well 52 internal medical residents understood the four modes of the interpersonal process recall (IPR) system after the students had received training in this system, and also investigated whether the students taught by instructors trained in the IPR system had a greater understanding of the system than those taught by nontrained instructors. Students were tested before and after the course, which involved extensive use of videotapes of interviews. With some reservations, the data as a whole suggest that the IPR system can be taught effectively by an enhancement of the methods used for this study and that the instructors do not have to receive training in the system to teach it effectively. PMID- 2923643 TI - Residents' hours and supervision. AB - One year of graduate medical education, the internship, had become the norm for graduates of most U.S. medical schools by 1920, and subsequently was adopted by most states as a criterion for licensure. The original concept of a "resident physician" carried with it responsibility for patients 24 hours per day, seven days per week. Recent public and media attention to the issues of residents' supervision and working hours has led to governmental efforts to restrict their hours and set minimum requirements for supervision. New York is the first state to impose specific requirements. The New York recommendations have implications for the concept of graded responsibility for residents, for learning the natural course of illness, and for the need to provide service in hospitals. Further, the recommendations raise four objections: they do not recognize differences by type of specialty or year of training; they might affect the length of time needed to acquire aggregate clinical skills; they affect different types of hospitals differently; and they would have a major effect on physician manpower. Hospitals and residency programs will face several difficult choices in responding to the regulations. To provide its members with guidelines for action, the Executive Council of the Association of American Medical Colleges has issued recommendations for residency hours and supervision, including the use of an 80 hour work-week averaged over four weeks, the continued use of graded supervision of residents in emergency rooms and in inpatient and ambulatory settings, and control of housestaff moonlighting. PMID- 2923644 TI - Use of student self-involvement to enhance nutrition education for first-year medical students. PMID- 2923645 TI - Geographic medicine: a new movement within international health. PMID- 2923646 TI - The regulation of hospital-based medical education. PMID- 2923647 TI - Sex differences in rank attainment among radiology and internal medicine faculty. AB - Overall, the percentage of women attaining the ranks of associate professor and professor remains well below the percentage of men in those ranks. Few studies of women in academic medicine have been conducted that might guide the leaders of medical schools and specialty societies in addressing the reasons for this disparity. The Association of American Medical Colleges (AAMC) Faculty Roster System allows comparison of a cohort of faculty at any selected time following their first faculty appointments. This study examined men and women faculty who received their first appointments in the departments of radiology and internal medicine in 1976 and who were still active in 1986. Disparities between men and women in rank attained were apparent in both specialties but were greater in radiology than in internal medicine. Other variables examined include ethnic racial self-description and teaching, research, patient care, and administrative responsibilities. The authors pose additional research questions requiring information that the Faculty Roster System is not designed to provide. PMID- 2923648 TI - Survey results and a recommendation for a change in U.S. medical physiology curricula. AB - Both the recent advances in molecular biology and the dilemma of teaching a larger volume of more detailed material to students from a declining, weaker applicant pool necessitate a critical reappraisal of the medical physiology curriculum and pedagogy. An extensive survey of the physiology curricula in 107 U.S. medical schools conducted during the 1986-87 academic year revealed that physiology was taught as a separate course, averaging 100.1 lecture hours, 24.0 laboratory hours (usually dealing with cardiovascular and pulmonary physiology), and 25.6 conference hours. The physiology courses offered by the schools surveyed averaged 21.8 weeks in duration and were taught by an average of 13 faculty (72.5% with Ph.D. degrees, 21.8% with M.D. degrees, and 5.4% with both M.D. and Ph.D. degrees). The evolution of the physiology curriculum has been slow; as a result the need for change is great. Physiology departments must give a high priority to reorganizing and revitalizing teaching. Additionally, the physiology curriculum must be critically examined. There is an urgent need to reevaluate course content, decide the fate of the student laboratory, and develop new, innovative teaching techniques. The ubiquity of these problems among medical schools suggests that they be addressed at a national level. PMID- 2923649 TI - Evaluation of procedural skills of internal medicine residents. AB - In 1983 the American Board of Internal Medicine mandated that training programs assess residents in procedural skills prior to board certification. Beginning in 1984, the University of Hawaii developed an assessment and testing program that consists of a three-phase evaluation process for qualifying internal medicine residents in basic procedural skills: an observation period spanning the three year residency, a 100-question multiple-choice examination, and a slide identification examination involving simple identification of body fluid elements. From 1984 through 1987 the mean scores of both examinations were analyzed for each level of residency and for each year of testing to assess whether curriculum changes were effective. There was a statistically significant improvement (p less than .005) in performance on both the multiple-choice and the slide-identification examinations as the residents progressed through the program. No difference in performance was found for the multiple-choice examination between calendar years, but a significant difference (p less than .01) was found for the slide-identification examination between calendar years. Despite perceptions by the faculty that their increased emphasis on the learning of procedural skills has been successful, the multiple-choice examination results over time do not support this belief. These findings suggest that residents need more structured curriculum guidelines to aid their learning and faculty members require better direction in the educational goals for procedural skills training. PMID- 2923650 TI - A survey to identify deficiencies in transfusion medicine education. AB - Medical faculty, blood center directors, and technologists were surveyed to assess current opinions of knowledge deficiencies in transfusion medicine among medical school graduates, housestaff, and practicing physicians. Over 90% of those responding believed additional training in transfusion medicine was needed. Nine categories of deficiencies were identified, with more than 40% of respondents' comments reflecting concern about the lack of knowledge of the use of blood and blood components. Clinical faculty and blood bankers differed in their assessments of the knowledge deficiencies in two of the nine categories. Information obtained in this survey is relevant to educational development in transfusion medicine. PMID- 2923651 TI - Academic performance of reapplicants to a medical school. AB - This study examined the academic performance of 399 reapplicants who had entered the University of Alabama School of Medicine between 1978 and 1984. Compared with the first-time applicants, the reapplicants had lower preadmission measures and a higher rate of academic difficulty during medical school. However, applicant status (that is, first-time or reapplicant) added nothing to the prediction of academic difficulty over what could be predicted by preadmission measures alone: the students with lower preadmission measures were more likely to experience academic difficulty, regardless of their applicant status. Based on these results, reapplicants should not be viewed negatively simply because they are reapplicants. PMID- 2923652 TI - Medical students' perceptions of cheating. AB - In 1985, 683 students at a large private upper-midwestern medical school were surveyed concerning the appropriateness of traditional cheating behaviors and behaviors related to professional misconduct and dishonesty in patient care. They also rated the acceptability of various rationalizations for these behaviors. The students agreed that traditional forms of academic cheating are inappropriate, but they did not agree about the appropriateness of certain behaviors in the areas of patient care and professional misconduct. PMID- 2923653 TI - A research methods and statistics journal club for residents. AB - A monthly journal club for residents that focuses on research methods and statistics is described. Detailed discussions and analyses of clinical research articles by the residents are used to teach the important concepts and principles of medical research in a manner useful to the practicing physician. Discussion of research articles is structured by a guide for presenting the research articles to the group and by stimulus questions that address specific methodological issues related to the study being examined. Residents have been enthusiastic in their evaluation of the journal club; the experience has stimulated some of them to conduct their own research studies. PMID- 2923654 TI - [The use of the jet ventilation technic in surgical interventions on the trachea]. AB - Based on our own experiences and on comparisons with the literature, we demonstrated the possibilities and problems of jet ventilation technique during surgical interventions at the trachea. This method has been applied 28 times and in two cases surgical manipulations caused complications in the form of bronchial bleedings, with the occurrence of hypoventilation in one case. Due to the essentially improved prerequisites for the surgeon and optimal ventilation, the procedure of jet ventilation presents a true enrichment of the anaesthesiological repertoire, provided the indications are well established and the cooperation between surgeon and anaesthetist is good. On the other hand, however, owing to insufficiencies in the adequate monitoring if this form of ventilation, a comparably higher risk for the patient has to be taken into account. PMID- 2923655 TI - Tongue protrusion mediated by spared anterior ventrolateral neocortex in neonatally decorticate rats: behavioral support for the neurogenetic hypothesis. AB - Many changes in anatomical organization and behavior follow circumscribed, neonatal cortical ablations. These include functional sparing and compensatory anatomical changes. An objective of this study was to examine the generality of such changes by reversing the usual experimental procedure, removing all cortex but a circumscribed area and examining whether the remnant made new anatomical connections, adopted new functions and whether it continued to subserve the typical functions of that area. All neocortex and cingulate cortex, except a small portion of anterior-lateral neocortex, which is normally involved in tongue and mouth use, was removed from one-day-old or adult rats. Fluorescent labelling and behavioral tests were used to evaluate its function. The results showed: (1) The remnant cortical tissue maintained similar connections in neonatal and adult groups and similar connections to those found in rats that had received no lesions. (2) The rats still displayed behaviors normally supported by this cortex, including tongue protrusion to obtain food and picking up and eating hard food efficiently. (3) Impairments were obtained on tests normally mediated by the ablated cortex, including skilled reaching and grooming. (4) When the cortical remnant was removed, tongue protrusion and efficiency of food consumption were similarly impaired in both neonate and adult groups. An additional serendipitous finding was a dissociation between two types of tongue movement: licking from a ventrally-located surface survived cortical removal but tongue protrusion did not. The results show that bilaterally spared small remnants of neocortex maintain normal functions and do not assume new functions or make new connections despite neonatal decortication. The results provide behavioral support for the neurogenetic hypothesis, which postulates that cortical circuitry is specified during early embryonic development. This suggests that there are constraints on neural remodelling and behavioral recovery following neonatal lesions. The implications of these results are discussed with respect to the documented remodelling and sparing that occur following partial or unilateral lesions within functional systems. PMID- 2923656 TI - Ontogeny of open field activity in rats after neonatal lesioning of the mesocortical dopaminergic projection. AB - In order to examine the effect of neonatal depletion of the dopaminergic mesocortical projection on the development of a prefrontal cortex-mediated behaviour the ontogeny of open field behaviour was studied after neonatal depletion of cortical dopamine. Cortical dopamine was depleted by neonatal thermal lesions of the ventral tegmental area (VTA). Medial VTA lesions caused a moderate dopamine depletion in the prefrontal cortex and an almost complete cortical serotonin depletion, and resulted in transient hyperactivity in the open field at postnatal day 25. More extensive VTA lesions produced an almost complete depletion of dopamine in the prefrontal cortex, but also affected the dopaminergic innervation of the nucleus accumbens, and resulted in a permanent hypoactivity in locomotor and exploratory behaviour in the open field. The effects of neonatal lesions of the mesolimbocortical projection are quite different from those made in adulthood. These results indicate in addition that, apart from the dopamine/noradrenaline balance, the serotonin/dopamine interactions in the frontal cortex may also be of importance in regulating open field activity. PMID- 2923657 TI - Effects of excitotoxic lesions of the substantia innominata, ventral and dorsal globus pallidus on visual discrimination acquisition, performance and reversal in the rat. AB - Rats received infusions of ibotenic acid into the substantia innominata, in the region of the nucleus basalis of Meynert (nbM), before and after training on simple (simultaneous) and conditional visual discriminations. The ibotenate infusions reduced cortical choline acetyltransferase (ChAT) levels by about 20%, destroyed many ChAT-immunoreactive neurons in the nbM, but also caused the loss of many neurons in the substantia innominata and adjacent areas. These lesions did not impair the acquisition and performance of a simple visual discrimination, but did impair reversal of the discrimination and the performance of a conditional visual discrimination. However, the degree of impairment was unrelated to the degree of cortical ChAT loss. Ibotenic acid lesions to the dorsal globus pallidus also impaired reversal of discrimination but left acquisition and performance unaffected. Striatal dopamine depletion produced by 6 hydroxydopamine (6-OHDA) infusions into the mid-ventral caudate nucleus impaired performance of the simultaneous visual discrimination. Cortical noradrenaline depletion produced by 6-OHDA lesions of the dorsal noradrenergic bundle either alone or in combination with ibotenic acid lesions of the substantia innominata had no effect on acquisition of the discrimination. It is concluded that ibotenic acid lesions of the substantia innominata or to the dorsal globus pallidus affect learning and performance of conditional visual discrimination performance and impair reversal learning without affecting the capacity to discriminate visual events. These results are compared to those following cortical noradrenaline depletion or striatal dopamine loss. PMID- 2923658 TI - Selective fimbria lesions impair acquisition of working and reference memory of rats in a complex spatial discrimination task. AB - It has been reported that transections of the fimbria-fornix or lesions of the hippocampus selectively impair spatial working memory. Disruptive effects of these lesions on reference memory performance, however, have also been reported. We studied the effects of selective fimbria lesions on the acquisition of a complex spatial discrimination in the cone field. The cone field task is a place learning task that permits the simultaneous assessment of working and reference memory performance. Reproducible bilateral stereotaxic lesions were made by knife cuts parallel to the midline. Sham lesions consisted of similar knife-cuts that were restricted to the overlying tissue. The rats were randomly started from 1 of 4 positions in order to prevent the development of a fixed food search pattern. On both memory components, fimbria-lesioned rats made about twice as many errors as the sham-lesioned and intact subjects, even after extensive training. Transection of the fimbria caused pronounced cholinergic denervation, predominantly at the more ventral part of the hippocampus, as indicated by reduced acetylcholinesterase histochemistry. Our results suggest a major role of the cholinergic innervation of the ventral hippocampus in spatial discrimination. PMID- 2923659 TI - In vivo modulation of septo-hippocampal cholinergic activity in mice: relationships with spatial reference and working memory performance. AB - Dopaminergic afferents to the septum mediate a tonic and trans-synaptic inhibitory control on the cholinergic neurones of the septo-hippocampal pathway. Lesion of these afferents using 6-hydroxydopamine (6-OHDA) results in a chronic and specific increase of hippocampal cholinergic activity in mice. The consequence of this in vivo modulation of hippocampal cholinergic activity on the acquisition of both a spatial discrimination and a working memory (delayed non matching to place) task in an 8-arm radial maze by C57BL/6 mice were investigated. Combined neurochemical and behavioural analyses revealed significant correlations between hippocampal sodium-dependent high-affinity choline uptake activation induced by testing and performance measures. In the first experiment 6-OHDA-treated mice compared to control and vehicle-injected mice showed a transient (day 2) but significant facilitation of their spatial discrimination performance which appears to be better related to the working but not to the reference memory component of the task. This hypothesis is strengthened by the results of the second experiment which shows an amelioration of working memory performance when the septo-hippocampal cholinergic pathway is specifically activated in vivo. PMID- 2923660 TI - Effects of hippocampal manipulations on the classically conditioned nictitating membrane response: simulations by an attentional-associative model. AB - The effects of various hippocampal manipulations on the classically conditioned nictitating membrane (NM) response were simulated by a real-time attentional associative model. The model incorporates: (a) a mechanism capable of establishing associations between conditioned (CS) and unconditioned stimuli (US) and between two CSs, (b) a mechanism that combines CS-CS and CS-US associations and builds 'computational cognitive maps', (c) an attentional rule that 'tunes in' relevant CSs and 'tunes out' irrelevant CSs, (d) performance rules that convert learning variables into topography of the rabbit NM response, and (e) rules that convert learning variables into neuronal firing. The present study explored three hypotheses regarding hippocampal function: (a) hippocampal lesions (HL) impair the 'tuning out' of irrelevant stimuli, (b) hippocampal stimulation (HS) and hippocampal long-term potentiation (LTP) facilitate the 'tuning in' of relevant stimuli, and (c) hippocampal unit activity is proportional to the instantaneous value of associative variables that participate in the 'tuning' mechanisms. Computer simulations for the HL case were carried out for conditioning under different interstimulus intervals (ISI) with different types of US, discrimination reversal, and sensory preconditioning. Computer simulations for the HS and LTP case were carried out for acquisition of delay conditioning and of classical discrimination. In addition, simulations of hippocampal unit activity during acquisition and extinction are presented. Under the 'tuning out' hypothesis for the HL case, the model proved capable of simulating a large portion of the experimental data, showing discrepancies with relevant literature only when describing HL effects on trace conditioning with shock US under short and long ISIs, trace conditioning with air puff US under long ISIs, discrimination reversal and sensory preconditioning. Under the 'tuning in' hypothesis regarding the HS and LTP case, the model proved capable of simulating acquisition of delay conditioning but not acquisition of classical discrimination. Under the assumption that neuronal activity is proportional to the instantaneous value of associative variables, the model is able to simulate hippocampal unit activity. PMID- 2923661 TI - The acquisition of visual and auditory discriminations in male and female Wistar rats. AB - Different groups of male and female Wistar rats were trained to discriminate between visual or auditory stimuli in a discrete-trial experimental procedure. Presentation of one of the two visual stimuli or one of the two auditory stimuli was immediately followed by a 5-s presentation of the two levers. A press on the left lever was followed by food if one stimulus had been presented, while food was presented following a press on the right lever if the other stimulus had been presented. Incorrect responses or failure to respond during level presentation was always followed by presentation of the same visual or auditory stimulus once the intertrial interval had again expired. This sequence was consistently repeated until a correct response occurred. Discrimination performance improved as training progressed. Acquisition of the visual and auditory discrimination did not differ between males and females, although males were more likely than females to respond effectively during repeated trials (those trials which were initially incorrectly completed or not completed at all). The results of the present experiment make it likely that behavioral differences between the sexes in other experimental procedures are not due to differences in sensory discrimination abilities. PMID- 2923662 TI - Electrical stimulation of lateral hypothalamic area and behavioural sequences in a lacertid lizard. AB - The observed transition frequencies of behaviour patterns were obtained for isolated lizards (Gallotia galloti), as well as those expected if the patterns were independent. The transitions differing significantly from random were calculated when: (1) the animals had an electrode in their lateral hypothalamic area (I); (2) they were electrically stimulated (S). The index O-E (O = observed transition frequency; E = expected one) was used to extract the statistical significance of the behaviour transitions. The Friedman and Wilcoxon tests, used to compare the relative transition frequencies between I, S and a first control (C) condition, showed that the main effects during the stimulation period were a decrease in the relative frequency of some transitions involving the climbing pattern and an increase in others including some exploration patterns. PMID- 2923663 TI - Modality specific type 2 theta production in the immobile rat. AB - The purpose of the present study was to compare the relative effectiveness of stimulation of different sensory modalities in eliciting Type 2 theta in the rat in the presence or absence of a ferret. Visual, auditory, and tactile stimuli were presented to rats in both conditions. Tactile stimulation produced more movement than either visual or auditory stimuli when the ferret was present. In both conditions, however, more Type 2 theta was observed in response to tactile or visual stimulation than to auditory stimulation. In the arousal condition, stimulation of tactile and auditory modalities resulted in significant increases in the amount of Type 2 theta produced. Input to the visual modality produced high levels of Type 2 theta production in both low- and high-arousal conditions. It is argued that Type 2 theta is not necessarily a precursor to movement but rather sensory processing while in a high state of arousal. PMID- 2923664 TI - Differences in cyclophosphamide-induced suppression of cricket predation in selectively bred strains of taste-aversion prone and resistant rats. AB - Cyclophosphamide-induced conditioned suppression of cricket predation was observed in taste-aversion-prone (TAP) but not in taste-aversion-resistant (TAR) rats. These TAP and TAR strains had been selectively bred for efficient or inefficient acquisition of cyclophosphamide-induced saccharin taste aversions (TAs). Equivalent preconditioning cricket predation was practiced by nonfasted subjects of both strains. TAR rats that ate crickets before a cyclophosphamide injection were thereafter voracious predators as were saline-injected and pseudoconditioning controls of both strains. However, conditioned TAP rats subsequently displayed a marked suppression of cricket predation. Predation can provide a deprivation-free and species-natural consummatory response for studies of strain differences in TA conditionability of TAP and TAR rats. In addition, the present results indicate that TAP and TAR strain differences in TA conditionability are not restricted to the saccharin solution that was the conditioned stimulus basis of prior strain development. PMID- 2923665 TI - Predictable and unpredictable shock stimulates gastric contractility and causes mucosal injury in rats. AB - The effects of tailshock on gastric contractility and lesions were investigated in rats exposed to 100 1-mA tailshocks while confined inside plastic tubes. A light preceded each shock in one group and was randomly presented with respect to shock in the other. Following the session, animals were given 3 hr of rest before being sacrificed. Contractility of the corpus of the stomach was measured by means of chronically implanted extraluminal force transducers. Contractility was measured in 10-min blocks and analyzed by computer. Lesions were quantified by inspection; quantitative histology was performed on corpus and antrum sections. Signaled (n = 13) and unsignaled (n = 17) shock stimulated high-amplitude gastric contractions in fasted rats, which continued for 2 hr after the shock session. Cumulative contractile activity (1.5-hr shock plus 2-hr rest) in shocked animals was twice that in restrained and unrestrained control animals (n = 19, p less than .05), and contractile activity had a 30%-40% greater average amplitude than after a meal. Compared with unrestrained controls, shocked rats had visibly more mucosal injury (2.2 +/- 0.5 mm2 vs. 0.1 +/- 0 mm2). Larger cumulative contractile activity was associated with a larger area of erosions (r = .36, p less than .05). Frequency and duration of contractions did not distinguish between shocked and unshocked groups. We conclude that in rats, signaled and unsignaled tailshock stimulates persistent, high-amplitude gastric contractions and is associated with injury of the mucosa of the stomach. PMID- 2923666 TI - Determinants of the nature of environmentally induced hypoalgesia. AB - Factors that determine whether naltrexone and pentobarbital anesthesia block the hypoalgesia produced by electric shock were investigated. The number of shocks delivered, the time since the last shock, and whether the subject is removed from the shock environment for testing were all found to be critical. One shock was followed by an initial hypoalgesia that was reversed by naltrexone but was not affected by pentobarbital. Moreover, this initial hypoalgesia was not eliminated by removing the subject from the shock apparatus. When testing was conducted in the shock context, this early hypoalgesia was followed by a hypoalgesia that was still reversed by naltrexone but differed from the early response in that it was eliminated by pentobarbital anesthesia. This second hypoalgesia did not occur when testing was conducted after removing the animal from the shock apparatus. Five shocks were also followed by two separable responses. Here the first response was also not reduced by pentobarbital, but it was not blocked by naltrexone. This initial response was also not prevented by removal from the shock context, but, again, the second response did not occur after removal. The pattern after 80 shocks was quite different. Here the hypoalgesic response did not appear to change in character across the 10 min of testing or with removal from the shock apparatus. The response persisted for 10 min in the shock context or after removal and was blocked by both naltrexone and pentobarbital throughout its entire duration. These results reconcile findings from different laboratories and bear on a number of theoretical models of stress-induced hypoalgesia. PMID- 2923667 TI - Dopamine and preparatory behavior: II. A neurochemical analysis. AB - Changes in the activity of dopamine-containing systems in relation to preparatory and consummatory feeding responses were investigated. In Experiment 1 rats were conditioned to associate food delivery with the presentation of a conditional stimulus (CS+). When sacrificed after exposure to the CS+ alone on a test trial, the ratio of the dopamine metabolite 3,4-dihydroxyphenylacetic acid to dopamine (DOPAC/DA ratio) was increased significantly in the nucleus accumbens. A similar trend in the ratio of homovanillic acid to dopamine (HVA/DA ratio) was also observed. Similar increases were observed in the striatum, but these were not statistically significant. In contrast, no increases were observed in the DOPAC/DA ratio or the HVA/DA ratio in either brain region when rats were permitted to consume an unsignaled meal for 7 min. These findings suggest that activation of dopamine terminals in the nucleus accumbens occurs during the anticipation of a meal, at which times the rat is engaged in preparatory feeding behaviors, but does not accompany the performance of short bouts of consummatory feeding behavior. PMID- 2923668 TI - Multisensory deficits in rats produced by acute exposure to cold swim stress. AB - Cold swim stress and morphine administration produce analgesia. Whether this was accompanied by changes in other senses was investigated. Analgesia was assessed with a tail-flick test; the sensitivity of the other senses was assessed using the ability of mild sensory stimuli (prestimuli) to inhibit the amplitude of a subsequently elicited acoustic startle response. In Experiment 1, auditory prestimuli were used. In Experiment 2, visual prestimuli were used. In each experiment, rats were exposed to cold-water swims followed by behavioral testing, warm swims followed by testing, and testing alone. This was repeated, substituting morphine injections followed by testing, vehicle injections followed by testing, or testing alone. Both cold swim stress and morphine produced reliable analgesia. Only cold swim stress interfered with the ability of the stimuli to inhibit startle. This reflects decreased sensitivity to auditory and visual stimulation caused by cold swim stress, which suggests that the resultant sensory deficits are more global than is currently believed. PMID- 2923669 TI - Effect of restricted cortical lesions on absolute thresholds and aphasia-like deficits in Japanese macaques. AB - The effect of small bilateral cortical lesions on pure-tone audiograms and on the ability to discriminate between two types of Japanese macaque coo vocalizations was determined in four Japanese macaques (Macaca fuscata). A lesion that included the middle portion of the superior temporal gyrus of both hemispheres, that is, the primary and secondary auditory areas, resulted in a partial hearing loss as well as an inability to discriminate the vocalizations. Lesions that included the ventral portions of the superior temporal gyrus of both hemispheres but spared auditory cortex on one side also resulted in a partial hearing loss but had either a small effect or no effect on the ability to discriminate the vocalizations. Bilateral ablation of the dorsal superior temporal gyrus and adjacent parietal and occipital areas did not appear to result in a hearing loss and had no effect on the ability to discriminate the vocalizations. These results suggest that a hearing loss may be produced by lesions that involve small portions of the ventral two-thirds of the superior temporal gyrus bilaterally although the resulting loss is not as great as that observed with larger lesions. However, the aphasia-like deficit appears to result from a lesion of primary and/or secondary auditory cortex. PMID- 2923670 TI - Behavioral spectral sensitivities of different retinal areas in pigeons. AB - The spectral sensitivity of the red and the yellow retinal fields of head-fixed pigeons was separately measured for wavelengths between 340 and 640 nm by a behavioral perimetric technique. Within this spectral range the mean spectral sensitivity of both fields was found to be maximal at 584 nm and minimal at the lower ultraviolet wavelengths. Differences in sensitivity were found, however, at shorter wavelengths, with the yellow field being more sensitive than the red at wavelengths below 500 nm and especially in the ultraviolet spectral range. These sensitivity differences are discussed in relation to other functional differences between the pigeon's retinal fields. PMID- 2923671 TI - A role for the medial region of the amygdala in mineralocorticoid-induced salt hunger. AB - Damage to the medial region of the amygdala abolished aldosterone-induced salt hunger in the rat. In contrast, the salt hungers that are induced by adrenalectomy or by acute sodium depletion are left intact by the same brain damage. We suggest (a) that we have identified part of the neural circuit by which aldosterone participates in the genesis of salt hunger in the intact, sodium-depleted rat and (b) that these results provide further evidence for the hypothesis that there are separate receptive systems in the brain for the participation of aldosterone and angiotensin in the arousal of salt hunger. PMID- 2923672 TI - Prior episodes of sodium depletion increase the need-free sodium intake of the rat. AB - Prior episodes of sodium depletion increase the daily 3% NaCl intake of rats. They ingest large volumes and continue to do so for as long as 3 months after recovery from sodium deficit while eating sodium-rich food and while plasma sodium concentration and renal function are normal. The increased daily intake of sodium is, therefore, need-free. There is a marked sex difference in the need free intake of 3% NaCl. Female rats drink more salt than do male rats when they are sodium replete and depletion naive. Repeated depletions raise the need-free intakes of both sexes but the effect is greater in females. Plasma concentrations of angiotensin II and aldosterone, which are markedly elevated by each episode of sodium depletion, return to basal levels between and after depletions, and are not the cause of the chronically increased need-free salt intake of the multi depleted rat. These results suggest that the persistent increase in daily 3% NaCl intake that occurs in the rat with a history of repeated sodium depletions is a permanent, nonpathological increase in avidity for the taste of salty substances that results in life-long overconsumption of salt. PMID- 2923673 TI - Inhibition by diazepam of the effect of additional training and of extinction on the retention of shuttle avoidance behavior in rats. AB - Rats were submitted to a training and a test session in a shuttle avoidance task. In some groups, a second training session was interpolated 2 or 24 hr after the first session. In others, a session of extinction was interpolated 2 or 24 hr after the training session. When the interpolated task was 2 hr after training, training-test interval was 24 hr. When the interpolated task was 24 hr after training, training-test interval was 48 hr. The additional training enhanced, and the extinction depressed, retention test performance. Diazepam, given 30 min prior to the first (or only) training session enhanced the performance of avoidance responses in that session but inhibited it in the subsequent retention test. Diazepam given 90 min after training had no effect on retention. Diazepam given 30 min prior to either the additional training session or the extinction session did not affect performance in that session but cancelled their effects on retention test performance. The effects are related to the previously described prevention by diazepam of interfering effects on memory. PMID- 2923674 TI - Stimulation of the lateral septum is a more effective conditioned stimulus than stimulation of the medial septum during classical conditioning of the eye-blink response. AB - Eight rabbits were trained in the classically conditioned eye-blink response procedure using stimulation of the septal nuclei as the conditioned stimulus (CS). Each rabbit was trained with both medial septal stimulation and lateral septal stimulation. Stimulation of the medial septum was a far less effective CS than stimulation of the lateral septum. This effect may be due to the different roles of these two nuclei in classical conditioning. Conditioning using lateral septal stimulation as a CS is dependent on the cerebellar interpositus nucleus as is conditioning using peripheral and other brain stimulation CSs. PMID- 2923675 TI - Influence of the mesocortical dopaminergic system on activity, food hoarding, social-agonistic behavior, and spatial delayed alternation in male rats. AB - In order to assess the behavioral role of the dopaminergic mesocortical input to the prefrontal cortex, bilateral lesions were made in the ventral tegmental area (VTA). The possibility of a functional recovery by the administration of a dopamine agonist was examined. General activity, food hoarding, social-agonistic behavior, and spatial delayed alternation performance were recorded in rats with VTA lesions and in sham-operated animals. In the open field animals with VTA lesions were more active but showed less anxiety. Food hoarding was impaired. In dyadic interactions with sham-operated opponents, VTA rats were socially more active, whereas sham operates performed more keeping down and aggressive grooming. This behavioral deficit was partially recovered when apomorphine was administered prior to testing. VTA animals were impaired in the performance of a spatial delayed alternation task with an intertrial interval of 15 s, whereas no impairment was found with a 0-s intertrial interval. The theoretical implications of these findings are discussed. PMID- 2923676 TI - Antidromically identified striatonigral projection neurons in the chronically implanted behaving rat: relations of cell firing to amphetamine-induced behaviors. AB - The effects of systematically administered amphetamine (0.25-5.0 mg/kg, sc) on neostriatal neurons recorded in chronically implanted behaving rats were studied. Projection neurons, identified by antidromic activation from the substantia nigra, fired very infrequently during most predrug behaviors (e.g., median rate, 0.02 spikes per second during locomotion; 17 of 18 fired less than 1 spike per second during all rated behaviors). Nonantidromic cells also tended to fire slowly (median rate, 0.02 spikes per second during locomotion; 20 of 24 cells fired less than 1 spike per second). Cells of both type showed up to 10-fold variations in firing rate across behaviors. For most neurons, amphetamine caused a reduction in the firing rate during related pre- and postdrug behaviors. For instance, the firing rate of 28 of 42 neurons was reduced during the initial amphetamine-induced locomotion as compared with the rate during predrug locomotion. Moreover, with the higher doses of amphetamine, there was a further reduction in firing rate corresponding to the transition from locomotion to stereotypies. In contrast to previous studies, which suggest that amphetamine generally increases neostriatal firing rate in behaving animals, these results suggest that amphetamine inhibits the numerous slowly firing neostriatal neurons, many of which were identified as projection neurons. Thus amphetamine alters the magnitude and pattern of neostriatal control of its neural targets. PMID- 2923677 TI - Brain transplants enhance rather than reduce the impairment of spatial memory and olfaction in bulbectomized rats. AB - The possibility to compensate the loss of olfactory and non-olfactory functions due to removal of the olfactory bulb by embryonal brain grafts was investigated in adult rats. Spatial working memory was examined in an 8-arm radial water maze task 6 weeks after bulbectomy. During 15 daily trials, performance gradually improved in bulbectomized controls (n = 10) and in rats with olfactory bulb transplants (n = 9), but did not attain that of intact controls (n = 10). No improvement was observed in the rats with substantia nigra grafts (n = 8). Eleven weeks after bulbectomy, the same rats were tested in the water tank navigation task. The performance improved during ten 12-trial sessions in bulbectomized rats less than in intact controls, but more than in the transplanted rats. The olfactory food retrieval test performed 14 weeks after bulbectomy revealed almost full recovery of smell in bulbectomized rats, but not in the transplanted animals. It is concluded that the spatial memory deficit is probably due to bulbectomy-induced interference with septohippocampal function which is not alleviated, but rather enhanced by transplantation. The results suggest that the effect of brain grafting is not always beneficial. PMID- 2923678 TI - Water deprivation optimizes hippocampal activity and facilitates nictitating membrane conditioning. AB - The effects of water deprivation on hippocampal responsiveness and behavior during nictitating membrane (NM) conditioning were assessed in 12 New Zealand White rabbits (Oryctolagus cuniculus). The results showed that water deprivation produced a significant shift in electroencephalographic (EEG) frequencies such that deprived rabbits had a higher proportion of 2-8 Hz activity than did ad-lib controls. In subsequent NM training, the rabbits took significantly fewer trials to reach criterion (M = 66 vs. M = 117). A correlation coefficient quantitatively describing the relation between pretraining EEG patterns and subsequent learning rate was highly significant (r = .84). Multiple-unit analyses indicated that deprivation enhanced hippocampal responsiveness to the conditioning stimuli, especially early in training. It was concluded that the hippocampus is responsive to motivational level and that one role of the hippocampus is in the nonassociative, modulatory processes that affect the rate of conditioning. PMID- 2923679 TI - Impaired learning of classically conditioned bradycardia in rats following fourth ventricle administration of D-Ala2-methionine-enkephalinamide. AB - Prior to differential classical conditioning on two successive days, three groups of rats received an infusion (10 micrograms) of either the opioid peptide D alanine2-methionine-enkephalinamide (DALA), DALA plus naltrexone (5 micrograms), or saline into the rostral region of the fourth ventricle. A fourth group, which served as a control to help localize DALA's site of action, received an infusion of DALA (10 micrograms) into the brain stem area on the floor of the ventricle. The group given DALA alone in the ventricle showed no evidence of a heart rate conditioned response (CR) either during conditioning or during a nondrug test session given 2 days after conditioning. Interference with the CR by DALA was reversed by the concomitant infusion of naltrexone. The control group given DALA in the brain stem developed a normal CR. It was suggested that DALA-induced opioid-receptor activity in the region of the periaqueductal/periventricular gray or locus coeruleus region of the ventricle may have prevented the learning of a CR. This could have occurred through a blunting of the emotional aftereffects of the unconditioned stimulus or through interference with projection pathways to other areas. PMID- 2923680 TI - Retrospective and prospective coding of information: dissociation of parietal cortex and hippocampal formation. AB - Animals with sham operations, hippocampal formation, or small and large parietal cortex lesions were trained in a task that required memory for short or long lists of items (spatial locations). More specifically, on any one trial, a rat is presented with 2, 4, 6, 8, or 10 items (spatial locations) on a 12-arm radial maze followed 15 min later by a win-shift test that required the animal to choose between a place previously visited and a novel place. Sham-operated animals showed an increase in errors as a function of set size (2 to 8 items) followed by a decrease in errors with a set size of 10 items, suggesting the use of both retrospective and prospective memory codes. In contrast, animals with hippocampal formation lesions made errors for all set sizes, reflecting an inability to use a retrospective and prospective memory code. The failure to use a prospective code is probably a function of the inability to use a retrospective code (i.e., the animal needs to remember first what has occurred before it can determine what information lies ahead). Animals with small or large parietal cortex lesions made most of their errors for the longest list length, reflecting an inability to shift from a retrospective to prospective memory code. This dissociation between the hippocampal formation and parietal cortex might reflect mediation of different memory operations. The hippocampal formation might mediate new incoming information (data-based memory processing) and thus accentuate the importance of a retrospective memory code. The parietal cortex might mediate existing knowledge (expectancy-based memory processing) and thus facilitate the utilization of a prospective memory code. PMID- 2923681 TI - Differential ontogeny of working memory and reference memory in the rat. AB - In two experiments we examined the ability of 15-, 21-, and 27-day-old rats to perform two spatial working memory problems (delayed alternation and discrete trials delayed alternation) and a reference memory problem (position habit) in a T-maze. In the delayed alternation problem, each animal was presented with a series of free-choice trials and was rewarded for regularly alternating responses to the left and right arms of the T-maze. In the discrete-trials delayed alternation problem, each animal was forced to one maze arm and rewarded (forced run) and was then placed back into the start box and given a choice of arms (choice run). The direction of forced runs followed an irregular, counterbalanced series, and animals were rewarded for choosing the alternate maze arm on choice runs. In the position habit problem, animals were rewarded for consistently choosing one of the two arms of the T-maze. Performance on these problems was assessed relative to control conditions in which reward was not contingent on choice behavior. At all ages, rat pups learned to perform the delayed alternation and position habit problems (Experiment 1). However, only 21- and 27-day-old rats were able to learn the discrete-trials delayed alternation problem. The 15-day olds were unable to learn this task (Experiment 2). The results of these experiments show that reference memory capacity is present by at least 15 days of age in the rat and does not develop further at later ages.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2923682 TI - Biological waste treatment. PMID- 2923683 TI - Symposium. Blood pressure mechanisms and the sympathetic nervous system. June 20, 1988, New York. Proceedings. PMID- 2923684 TI - Tobaccoism in America. Twenty-five years of progress. PMID- 2923685 TI - Surgical considerations in the open rhinoplasty approach to closure of septal perforations. AB - Repair of nasoseptal perforations is a difficult problem for the otolaryngologist. Recently, there has been an increased incidence among patients, particularly with the rise in cocaine abuse and trauma. The variety of proposed methods of repair points to the lack of a definitive solution for successful surgical treatment of nasoseptal perforations. Successful septal perforation repairs using an open rhinoplasty approach with bipedicled mucoperichondrial flaps and temporal fascia grafts were achieved in eight of nine patients in a series. Resident otolaryngologists in training were the primary surgeons in all nine patients. The open rhinoplasty approach affords better exposure to the septal perforation than does a closed technique, and it facilitates the elevation of mucoperichondrial flaps on all sides of the perforation. This method also allows the surgeon access to perform a limited concurrent rhinoplasty when indicated. The open rhinoplasty approach is ideally suited for teaching the technique of large septal perforation closure in surgical training programs. The surgical considerations in using this method are discussed. PMID- 2923686 TI - Posterior nasal packing. Are intravenous antibiotics really necessary? AB - The use of antimicrobial prophylaxis in the presence of posterior nasal packing for the treatment of posterior epistaxis remains controversial. Twenty patients were prospectively randomized into this placebo-controlled, double-masked pilot study to receive either placebo or cefazolin sodium. Antibiotic-impregnated posterior gauze packing was employed in all patients. No infectious complications were noted in either group. The packings from the patients in the placebo group were foul smelling and heavily colonized with gram-negative bacteria while the packings from the antibiotic group were odor-free and lightly colonized with gram positive organisms. This preliminary study suggests the usefulness of antimicrobial prophylaxis for preventing complications from posterior nasal packing, although a larger sample size will be needed to decrease the type II (beta) error. PMID- 2923687 TI - The cause of nasal sinusitis in patients with cleft palate. AB - To determine the reason for the high incidence of nasal sinusitis in patients with cleft palate, the type of cleft, degree of nasal septal deviation, velopharyngeal function, and presence of pharyngeal flap were investigated in relation to nasal sinusitis. We also examined the relationship between the side of sinusitis and the cleft side in patients with unilateral cleft palate. Development of maxillary sinus, nasal mucociliary transport, and ciliary beating frequency of ciliated cells were also examined. The saccharin test indicated that nasal mucociliary transport was impaired. This impairment is believed to be one of the reasons for the high incidence of sinusitis in patients with cleft palate. PMID- 2923688 TI - Auditory brain-stem responses in children with previous otitis media. AB - The auditory brain-stem responses (ABRs) of 18 children who received tympanostomy tubes due to well-documented history of otitis media with effusion (OME) were compared with a matched control group with little or no history of effusion. The subjects in the OME group had significantly longer ABR latencies for waves III and V, with the most compelling delay for wave III and the III-I interwave interval. Although wave I prolongation in the OME group was not significant, the possible contribution of a peripheral effect on the latencies of waves III and V was investigated. The typical gender effect for the ABR latencies was unaltered in the OME group, and there was no group by gender interaction. We suggest that although the data support increased ABR latencies for children with a history of OME, they do not establish a causal relationship. PMID- 2923689 TI - Middle-latency responses. II. Variation among stimulation sites. AB - We investigated the relationship between thresholds of the electrically evoked auditory brain-stem response (EABR) and the electrically evoked middle-latency response (EMLR), and the variation in EMLR thresholds and dynamic ranges with site of stimulation. The EABRs and EMLRs were recorded in albino guinea pigs in response to electrical stimulation at the round window, promontory, scala tympani, and modiolus. The EABR and EMLR thresholds were similar. There was no significant difference between thresholds for round-window and scala tympani stimulation. Amplitude/intensity functions for the EMLR differed with site of stimulation. The EMLR seems to be comparable with the EABR for assessing the electrical excitability of the auditory pathway with less electrical artifact contamination. In this respect, round-window and scala tympani stimulation sites are equally efficacious. PMID- 2923690 TI - Rheologic studies on middle ear effusions and their mucus glycoproteins. AB - The properties of pooled thick and thin middle ear effusions, from children with otitis media with effusion, were studied by viscometry. Mucus glycoproteins were responsible for effusion viscosity. Their percentage by weight in thick and thin effusions was 25% and 8.2%, respectively. N-acetylcysteine and 0.2 mol/L of mercaptoethanol caused a 39% viscosity drop in a 5-mg/mL glycoprotein solution, whereas S-carboxymethylcysteine had no effect. Treatment of thick effusions with 0.2 mol/L of mercaptoethanol initially caused a viscosity decrease followed by a gradual increase. Higher reducing agent concentrations (0.5 mol/L) caused a more rapid decrease followed by a rapid increase, presumably by causing nonspecific aggregation of reduced protein molecules. These results suggest that the concentration of and the time that a mucolytic is in the middle ear would be of prime importance in achieving the desired decrease in viscosity. PMID- 2923691 TI - Internal derangements of the temporomandibular joint. Pathological variations. AB - A retrospective analysis of 540 operated cases (740 joints) of internal derangements of the temporomandibular joint was carried out. Observations of this patient population provided the basis for describing pathological variations of internal derangements. Radiologic studies, including tomograms and arthrograms or magnetic resonance scans, and surgical/pathological findings were correlated with clinical data in each case. It was found that clinical manifestations varied in a characteristic way and were directly related to the degree of pathological change and time course. Various stages of internal derangements were identified. Pathophysiological mechanisms responsible for the observed changes, as well as clinical signs and symptoms and causal factors, were discussed. Internal derangements are organic lesions that appear to be progressive and are probably of traumatic origin. The view is given that internal derangements represent the basic pathological entity responsible for clinical manifestations of what has been known as the temporomandibular joint pain-dysfunction syndrome or similarly described conditions. Effective clinical management takes on new importance because progression to advanced degenerative states may occur. PMID- 2923692 TI - Simple mucodermal tracheoesophageal shunt method for voice restoration. AB - A newly devised simple primary tracheoesophageal shunt method, involving a mucodermal tunnel, was performed on 14 patients. Aspiration was prevented by percutaneous digital pressure on the shunt, with silicone or collagen injection around it, or the use of a voice prosthesis. The overall success rate was 79% (11/14). This method was an easy one-stage procedure that could be performed in about 15 minutes. PMID- 2923693 TI - Mandibulotomy in the irradiated patient. AB - Though the "mandibular swing," as an approach to certain upper aerodigestive tract malignancies, has been gaining popularity in recent years, there has been little reported as to the feasibility of this procedure in subjects who have received radical preoperative radiotherapy. We have recently reported the results of 23 such patients, and we now present an update. The results presented are of a retrospective analysis of 44 patients, 50% of whom received radical preoperative radiotherapy to fields including the osteotomy site. As in the previous study, there were no statistically significant differences between the complication rates in the irradiated and nonirradiated patient populations. All the patients were orally rehabilitated. PMID- 2923694 TI - Effect of albumin-bound furosemide on the endocochlear potential of the chinchilla. Alleviation of furosemide-induced ototoxicity. AB - The effects of albumin-unbound furosemide and albumin-bound furosemide on the cochlear function were compared by the continuous observation of the endocochlear potential (EP) in the chinchilla using the microelectrode method. The EP depression following the intravenous injection of 50 mg/kg of furosemide was 108.5 +/- 2.7 mV, while the addition of 1.0 and 1.3 g/kg of albumin induced the EP depression to be 35.0 +/- 4.8 and 8.1 +/- 1.9 mV, respectively, and both prolonged the time to attain the minimum EP. However, there was no difference in the recovery time of the EP between the two groups. The results indicate that access to the site of furosemide action in the cochlea is dependent on the unbound fraction of furosemide and that the albumin-bound furosemide alleviates the EP depression induced by furosemide alone with the augmentation of diuresis. PMID- 2923695 TI - Kawasaki disease and cervical adenopathy. AB - Kawasaki disease (KD) is an acute illness of unknown cause that affects infants and children. The diagnosis is confirmed in patients with prolonged fever and four of the following clinical features: (1) nonexudative conjunctivitis; (2) oral cavity changes; (3) rash; (4) extremity changes; and (5) cervical adenopathy. Complications of KD include coronary artery aneurysms, which may lead to myocardial infarction, chronic coronary insufficiency, or death. We describe a series of 83 patients with KD in whom 43 (52%) of 83 developed cervical adenopathy during their acute illness. Eighteen (42%) of these 43 patients were initially misdiagnosed as having cervical adenitis and were treated with antibiotics. The otolaryngologist may see these patients in referral and should consider the diagnosis of KD in patients with cervical adenopathy, prolonged fever, signs of mucosal inflammation, or rash. Early diagnosis and intravenous treatment with high-dose gamma-globulin is effective in reducing the prevalence of coronary artery abnormalities. PMID- 2923696 TI - Aberrant carotid artery. Presentation in the near midline pharynx. AB - Three cases of an aberrant internal carotid artery presenting at or near the midline in the posterior part of the pharynx occurred. In all three cases, the anomalous finding was not correlated with the presenting symptoms of the patient. In two of the three cases intraoral pulsations were detected during initial examination. In the third case, pulsations were appreciated on reexamination after roentgenographic evaluation. Intraoral photographs, computed tomographic scan, magnetic resonance imaging, and arteriography of these findings are shown. A review of the literature and the embryology of the lateral pharyngeal carotid artery are presented along with the rare finding of the near midline carotid artery and the clinical implications of this anomaly. PMID- 2923697 TI - Pathologic quiz case 2. Adult rhabdomyoma. PMID- 2923698 TI - Pathologic quiz case 1. Cervicofacial actinomycosis. PMID- 2923699 TI - Microbiology of the tonsils and adenoids. PMID- 2923700 TI - Significant increases in urinary dolichol levels in bacterial infections, malignancies and pregnancy but not in other clinical conditions. AB - The effect of different clinical conditions on urinary dolichols was studied in 219 hospital patients and in 24 pregnant women. Significantly increased urinary dolichol levels were found in patients with severe bacterial infections (mean +/- SEM, 37.5 +/- 8.0 micrograms/mmol creatinine, P less than 0.001), in patients with haematological or metastatic (23.3. +/- 5.1, P less than 0.05) as well as localised (15.4 +/- 1.8, P less than 0.01) malignancies and in pregnant women (22.2 +/- 1.8, P less than 0.001) as compared to healthy controls (6.6 +/- 0.4). These results show that urinary excretion of dolichols may be increased, not only in alcoholics and patients with some rare neurodegenerative storage diseases, but also in patients suffering from various other diseases. PMID- 2923701 TI - Social effects of a history of ischaemic heart disease. AB - The consequences of ischaemic heart disease include adverse personal and social effects as well as morbidity and mortality. This study describes these affects among people registered in a community-based study of all suspected heart attacks. Two groups were compared, those with and those without a previous history of ischaemic heart disease, using information about the subjects' lives before the event which caused them to be registered. Men with a history were more likely to be retired or permanently unable to work (64% compared with 47%). Despite some modification of risk factors, such as reductions of cigarette smoking, men (but not women) with a history were more likely to die from the registered event especially within one hour from onset of symptoms. These results emphasize the need for prevention of heart disease before it causes the effects and disabilities reported here. PMID- 2923702 TI - Dietary fats and platelet function among Finnish men. AB - The aim of this study was to elucidate the role of platelet aggregation as a risk factor for ischemic heart disease (IHD) and the relationship between fatty acids and platelet function. Platelet aggregation upon adenosine diphosphate (ADP), adrenaline and thrombin were measured in middle aged men in east and west, two regions of Finland with a nearly twofold difference in IHD mortality. Platelet aggregation results were correlated with the fatty acid compositions of plasma lipid fractions, adipose tissue triglycerides and platelet phospholipids. There was no significant east-west difference in platelet reactivity to ADP, adrenaline and thrombin. ADP-induced platelet aggregation showed significant negative correlations with all the platelet C20-C22 n-3 polyunsaturated fatty acids (PUFA), but significant positive correlations with the percentage of 18:2n-6 in adipose tissue and plasma cholesterol esters (CE) and triglycerides (TG). Adrenaline-induced aggregation correlated negatively with the percentage of 20:5n 3 in plasma CE and TG, and positively with the total percentage of saturated fatty acids in platelets. Aggregation upon thrombin had a negative correlation with the 20:3n-6/20: 4n-6 ratio in plasma CE and a positive correlation with 18:2n-6 in adipose tissue. The percentages of the major PUFA in platelets correlated significantly with the same fatty acids in plasma CE and phospholipids PL. Platelet 20: 5n-3 had a highly significant negative correlation with the percentage of 18: 2n-6 in plasma and adipose tissue lipids. Platelet 20: 4n-6 was unrelated to its precursors in plasma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2923703 TI - Fatty acids, platelets and monocytes. Something to do with atherogenesis. AB - A remarkable variation in monocyte activation among individuals was observed when blood from different people was incubated with lipopolysaccharides. To elucidate this phenomenon, we studied intracellular signals associated with monocyte activation. This was done by measuring induced thromboplastin synthesis. An inhibitor of phospholipase A2 blocked the lipopolysaccharide induced synthesis of thromboplastin. Thus, release of arachidonic acid (20: 4) seemed to be necessary to activate the monocytes. Nordihydroguaiaretic acid, a lipoxygenase inhibitor, had no effect on the monocyte activation in subjects with a low response to lipopolysaccharides (low responders); this contrasted with nearly 80% inhibition in individuals with very sensitive cells (high responders). Taking aspirin raised monocyte activation by an average of 50%, this was caused by the effect of aspirin on the platelets. Platelets enhanced the lipopolysaccharide activation of monocytes 2-3 fold. The high response phenomenon was partially due to platelets. When platelets in the blood of high responders were substituted with platelets from low responders, the monocyte activation fell by up to 70%. Fatty acids seemed to play a central role in the activation of monocytes. Intake of cod liver resulted in significant reduction of induced thromboplastin synthesis. It is suggested that those who are high responders may be more susceptible to developing atherosclerosis. PMID- 2923704 TI - Effect of dietary lipids on platelet function and thrombosis. AB - In rats, diets rich in polyunsaturated fatty acids of the (n-6) and (n-3) families (P) reduce the tendency to arterial thrombosis, whereas diets containing long-chain saturated fatty acids (S) are prothrombotic. Monounsaturated fatty acids seem to have a neutral influence on arterial thrombus formation. Consequently, the P/S ratio is an important determinant of the thrombogenicity of a dietary fat, the effect of which is probably mediated by an influence on platelet aggregability. In man, the type of dietary fat also affects platelet aggregation. Methodological problems, however, have resulted in equivocal results from studies, especially with respect to diets enriched with fish oil. Therefore, more research is required with methods than can quantify thrombotic risk in a reliable way. Nevertheless, the available evidence already justifies an active policy to increase people's consumption of (poly)unsaturated fatty acids at the expense of long chain saturated fatty acids. PMID- 2923705 TI - Antioxidants and platelets. AB - It is postulated that antioxidants reduce platelet activity by the stimulation of prostacyclin synthetase by scavenging synthesis-inhibiting peroxides. The experimental and clinical evidence supporting this theory is inconclusive. Clinical trials suggest that vitamin E reduced platelet aggregability. Nonexperimentally, a strong association has been observed between low serum selenium concentration and increased platelet aggregability. These findings suggest that antioxidants have an important role in the regulation of platelet function. PMID- 2923706 TI - Removal of an intrauterine device and the treatment of acute pelvic inflammatory disease. AB - The effect of removing intrauterine devices on the resolution of acute pelvic inflammatory disease was retrospectively studied in 186 hospital inpatients. In 105 patients the intrauterine device was left in place and in 81 it was removed on admission. The demographic and clinical findings in the two groups were similar. No differences were found between the two groups in their short-term response to treatment, except that when an intrauterine device was removed the time in hospital was more often prolonged. PMID- 2923707 TI - Attempted clinical application of a technique for promoting robust free recall to a case of alcoholic Korsakoff's syndrome. AB - A case study is reported which attempted to teach personal orienting information (i.e., recent history) to an amnesic male patient. The structured cuing methods reported by Kovner, Mattis, and Pass (1985, Journal of Clinical and Experimental Neuropsychology, 7, 395-411) were adopted. This involves structured presentation and cuing of target words embedded in a narrative. Some patients eventually are able to freely recall large amounts of material presented in this way. In the present case, the patient received 30 training sessions over 8 weeks. The material to be remembered was 10 target words pertaining to recent personal history. These words were embedded in accompanying storyline. The patient's immediate recall at the end of each session improved to some extent over the training period. However, delayed recall for the material remained nil throughout. Twelve months after the last training session the patient showed some "implicit" retention of the material. The findings are contrasted with Kovner et al.'s dramatic results and discussed. PMID- 2923708 TI - The role of the hemispheres in closed loop movements. AB - The purpose of these experiments was to determine if the two hemispheres play different roles in controlling closed loop movements. Subjects were asked to move to a narrow or wide target in the left or right hemispace. Reaction time (RT) was faster for the left arm of normals, only in the right hemispace, but there were no differences between arms in movement execution. Right but not left hemisphere stroke (CVA) patients showed longer RTs for the contralateral but not ipsilateral arm. The right CVA group's ipsilateral movement, especially to narrow targets was less accurate. The left CVA group's RT did not benefit from advanced information, but ipsilateral movement execution was normal. These results were discussed in terms of inter- as well as intrahemispheric control of programming and execution of closed loop movements. PMID- 2923709 TI - Unilateral nostril breathing influences lateralized cognitive performance. AB - Relative nostril efficiency (nasal cycle) is related to hemispheric EEG differences and performance on cognitive tasks. We investigated how unilateral forced nostril breathing influences spatial and verbal performance. Right-handed males and females performed both tasks under either left-nostril, right-nostril, or free-breathing conditions. Unilateral breathing affects performance differently in males and females. It influences male performance ipsilaterally on both tasks: Their spatial performance is better during right-nostril breathing, and their verbal performance is better during left-nostril breathing. Unilateral breathing influences female performance contralaterally, but only on the spatial task: Their spatial performance is better during left-nostril breathing. These differences within and between sexes may exist because unilateral nostril breathing differentially activates the two hemispheres and thereby facilitates performance, or because attempts of the brain to control the nasal cycle unilaterally interfere with performance. PMID- 2923710 TI - Memory deficits before and after temporal lobectomy: effect of laterality and age of onset. AB - Laterality and age of onset effects on semantic and figural memory were evaluated in 30 right-handed, left speech dominant (amobarbital test) patients with epilepsy before and after temporal lobectomy. There were no effects of focus on WAIS-R IQ scores. Early onset (less than or equal to 5 years) was associated with lower IQ and memory (WMS). Left Temporal (LT) patients showed worse semantic than figural memory preoperatively. Unexpectedly, early onset LT had marked postoperative decline of figural memory, whereas late onset LT patients showed the previously reported worsening of semantic memory. Right Temporal (RT) lobectomy patients, in contrast, improved in both semantic and figural memory regardless of age of onset. A "crowding effect" was suggested by the decline in figural memory following surgery in the early onset LT patients who remained stable or improved in semantic memory. Results indicate the need to incorporate age of onset of seizures into laterality models of memory function following unilateral temporal-hippocampal resection. PMID- 2923711 TI - Laterality effects in identification of caricatures and photographs of famous faces. AB - Recent evidence suggests that memory representations of familiar faces may exaggerate distinctive information as do caricatures (G. Rhodes, S. Brennan, & S. Carey, Cognitive Psychology, 1987). Therefore caricatures should be effective representations of faces and should yield a right hemisphere processing advantage, as do photographs of faces. Photographs and caricatures of famous faces were presented to the left visual (LVF), the right visual field (RVF), and centrally (CVF), in a name-face verification task. There was a LVF (right hemisphere) advantage for both caricatures and photographs on name-face mismatches but no VF difference for matches. These results were true for both accuracy and reaction time. Processing strategy differences that may account for the difference between matches and mismatches are discussed. Performance was generally better for photographs than for caricatures, irrespective of visual field condition. PMID- 2923712 TI - Performance in free recall following rupture and repair of intracranial aneurysm. AB - There have been many reports of global memory disorder following rupture and repair of intracranial aneurysms. These reports suggest a more anterior basis for the amnesic syndrome than the various sites in the diencephalon and the temporal lobe that have so far been implicated. Patients from a consecutive series of 76 cases of aneurysmal subarachnoid hemorrhage demonstrated a moderate deficit in free recall, but aneurysms at different sites within the cerebrovascular system did not produce significantly different degrees of impairment. The results are consistent with the idea that aneurysmal subarachnoid hemorrhage gives rise to diffuse cerebral damage, and do not necessitate any revision of conventionally accepted accounts of the neuropathology of amnesic conditions. PMID- 2923713 TI - Recognition of affective and noncanonical linguistic facial expressions in hearing and deaf subjects. AB - This study explores the use of two types of facial expressions, linguistic and affective, in a lateralized recognition accuracy test with hearing and deaf subjects. The linguistic expressions represent unfamiliar facial expression for the hearing subjects whereas they serve as meaningful linguistic emblems for deaf signers. Hearing subjects showed left visual field advantages for both types of signals while deaf subjects' visual field asymmetries were greatly influenced by the order of presentation. The results suggest that for hearing persons, the right hemisphere may predominate in the recognition of all forms of facial expression. For deaf signers, hemispheric specialization for the processing of facial signals may be influenced by the differences these signals serve in this population. The use of noncanonical facial signals in laterality paradigms is encouraged as it provides an additional avenue of exploration into the underlying determinants of hemispheric specialization for recognition of facial expression. PMID- 2923714 TI - Intrahemispheric sex differences in the functional representation of language and praxic functions in normal individuals. AB - Kimura (1980, The Behavioral and Brain Sciences, 3, 240-241; 1983, Canadian Journal of Psychology, 37, 19-35; 1987, Canadian Psychology, 28, 133-147) recently proposed that there are intrahemispheric sex differences in the organization of particular language and praxic functions such that in females these functions are more focally represented. This hypothesis, as well as supporting data, was derived from research with brain-injured subjects. The purpose of the present study was to test the utility of using dual-task methodology for investigating sex-related variation in intrahemispheric functional organization in normal individuals. Women were found to show greater interference than men on concurrent tasks of language and right-hand finger tapping. In support of Kimura's model, the present findings yielded evidence suggestive of intrahemispheric sex differences in the "functional distance" between language and praxic functions within the left hemisphere of normal individuals. PMID- 2923715 TI - Neuropsychological functioning in hemiparkinsonism. AB - A standardized neuropsychological battery including measures of intellectual cognitive, memory, attention-concentration, language, abstraction and mental flexibility, and sensory and motor functions was administered to 21 hemiparkinsonian patients (14 with right side and 7 with left side symptoms) and 17 controls matched for age and education. Patients were impaired in all functions except sensory. For motor functions, impairment was ipsilateral to the side of symptoms. For cognitive functions, right side symptoms were associated with verbal deficits whereas left side symptoms were associated with spatial deficits. Thus, a pattern of neuropsychological deficits consistent with the lateralization of motor symptoms may appear in the early stages of the disease. PMID- 2923716 TI - Differential effects of congenital left and right brain injury on intelligence. AB - IQ performance was compared in 28 prepubertal children with unilateral left vs. right hemisphere preperinatal injury. Results indicated statistically superior FSIQ and VIQ in the left-lesioned group. Findings were interpreted as consistent with the hypothesis of a left-right maturational gradient, whereby early right hemisphere damage has a more severe effect on overall intellectual functioning than early left injury. Findings also lend support for a greater crowding effect, as seen in the sparing of verbal skills, after early left hemisphere injury. PMID- 2923717 TI - Hemihypokinesia after right hemisphere stroke. AB - We tested the hypothesis that the right hemisphere is dominant for motor activation of "intention." If the right hemisphere is dominant for intention and if intention is a prerequisite for movement, motor impairment should be worse after an infarct in the right hemisphere than in the left. We asked nine subjects with right and nine with left hemisphere infarcts to elevate each shoulder independently. Subjects with right hemisphere lesions had more trouble moving the contralateral shoulder. The data are consistent with the hypothesis that the right hemisphere is dominant for motor activation or intention. PMID- 2923719 TI - Equivalent spatial location memory deficits in rats with medial septum or hippocampal formation lesions and patients with dementia of the Alzheimer's type. AB - College students, healthy elderly subjects, patients diagnosed with mild or moderate dementia of the Alzheimer's type, as well as rats with small or large lesions of the medial septum (MS), dorsal hippocampal formation (DHF) or nucleus basalis magnocellularis (NBM) were tested on an item memory task for a five- or six-item list of varying spatial locations. Equivalent patterns of item memory deficits as a function of serial order position were observed in rats with small or large MS or DHF lesions and patients with mild or moderate dementia of the Alzheimer's type. No deficits were found for NBM-lesioned rats. The results provide support for the possibility that rats with MS and DHF lesions mimic the mnemonic symptomatology of patients with Alzheimer's disease. PMID- 2923718 TI - Mental rotation: an event-related potential study with a validated mental rotation task. AB - Event-related potentials (ERPs) were recorded while subjects performed a validated mental rotation task, taken from the cognitive psychology literature. These ERPs show a late posterior negativity relative to a baseline condition requiring all of the same perceptual and cognitive processes except for the mental rotation itself. Our tentative identification of this posterior negativity with mental rotation is further supported by the finding that it varies systematically with the amount of mental rotation required on a trial by trial basis in the experimental task. We conclude that this late negativity is an ERP marker of the mental rotation process, and that this process engages primarily posterior brain regions. PMID- 2923720 TI - Application of expert systems to mammographic image analysis. AB - A prototype expert system was designed for differentiation of 16 circumscribed breast abnormalities utilizing findings identified by a human observer from X-ray mammograms, clinical data, and patient history. An off-the-shelf expert system shell served as the foundation for the rule base. The system runs on standard microcomputer hardware. Preliminary results suggest the expert system may be valuable in improving the ability of relatively unskilled observers to screen X ray mammograms. Overall, radiology residents with limited experience in mammographic image analysis obtained a diagnostic accuracy level of 40% on their own, whereas they attained 73% accuracy level when using the expert system. A group of biomedical engineering students with no prior experience in mammographic image analysis obtained on the average an 80% diagnostic accuracy level utilizing the expert system in comparison with the 70% average accuracy level obtained by practicing radiologists without use of the system. PMID- 2923721 TI - Nonthromboembolic causes of high-probability lung scans. AB - Three cases of high-probability lung scans because of nonthromboembolic causes (dissecting thoracic aortic aneurysm, sarcoid with venous occlusion, and subclavian catheter misplacement) are presented along with a review of the literature. PMID- 2923722 TI - Comparison of rest and exercise thallium-201 kinetics in man and implications for quantitation. AB - To develop a technique for quantitative analysis of resting thallium scintigrams, an understanding of thallium kinetics at rest is required. This study evaluates in normal man the thallium distribution and washout rates of thallium at rest and compares these findings to similar data obtained during exercise. The thallium half-life in normal resting myocardium is significantly longer than after exercise, 10.2 +/- 1.4 hours versus 3.9 +/- 0.3 hours (P less than .01). Differences in resting thallium half-life exist between the anterior, 45 degrees left anterior oblique (LAO), and 70 degrees LAO views and are 11.4 +/- 1.0, 10.6 +/- 1.0, 8.8 +/- 0.7 hours, respectively (all significantly different from each other by ANOVA, P less than or equal to .01); these differences are related to the imaging sequence. After exercise, the thallium half-life also varies according to imaging sequence, but in the opposite direction; i.e., anterior, 45 degrees LAO, and 70 degrees LAO views are 3.6 +/- 0.1, 3.9 +/- 0.3, 4.2 +/- 0.3 hours, respectively (P less than or equal to .01). Since imaging sequence and time of acquisition at rest and exercise were similar, this finding may be related to earlier maximal uptake of thallium after exercise as compared to rest. There are also significant segmental differences in thallium half-life at rest in the 45 degrees LAO view (9.8 +/- 0.9, septal vs. 11.0 +/- 0.9, posterolateral, P less than .01) and 70 degrees LAO view (8.3 +/- 0.4, anteroseptal vs. 9.2 +/- 0.6, inferior, P less than or equal to .01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2923723 TI - 'President's new year message'. PMID- 2923724 TI - 'The great debate'. PMID- 2923725 TI - 'Patient safety in general anaesthesia'. PMID- 2923726 TI - Who is tackling dental disease? PMID- 2923727 TI - 'Dentists causing harm with X-rays'. PMID- 2923728 TI - The possible dental effects of children's rusks: laboratory evaluation by two different methods. AB - In response to concern over the sugar content and possible dental effects of infants' rusks, a programme of research was undertaken to compare six different kinds of rusk with respect to (a) their cariogenicity in caries-active laboratory rats; (b) their capacity to serve as substrates for acid production by oral microorganisms, and the attack of this acid on dental mineral; (c) the adhesiveness of the rusks to the enamel surface. The caries scores in the animal experiments ranged from very high, with rampant dental destruction, for 31% sucrose rusks, down to virtually non-cariogenic on a zero-sucrose variety. With only one anomaly, cariogenicity correlated well with sucrose content. The results of the studies in vitro showed good general agreement with the animal data. The sucrose in the rusks, rather than their content of other sugars such as glucose, maltose and lactose, etc, emerged as a major factor in determining their effect on teeth, but cereal components can also play a part in governing adhesiveness and fermentability. PMID- 2923729 TI - Report of a survey conducted by the Consultant Orthodontists Group. The nature and distribution of clinical assistant posts in orthodontics in the United Kingdom in 1987. AB - This paper describes and discusses the results of a survey, conducted by the Consultant Orthodontists Group in the United Kingdom in 1987, which examined the nature and distribution of clinical assistant posts, and consultants' attitudes to the concept of appointing orthodontic auxiliaries. This survey demonstrated a large regional variation in the number of clinical assistant posts and in the number of 'specialist practitioners' and community orthodontists. More than 90% of consultants teach their clinical assistants how to use removable appliances, headgear and simple fixed appliances. More than 70% of consultants also teach their clinical assistants how to use multi-bracketed techniques and functional appliances. Ninety-one per cent of consultants would give their support to developing regional training schemes for clinical assistants in orthodontics. Eighty-eight per cent of consultant orthodontists favoured the appointment of orthodontic auxiliaries to carry out intra-oral work, and 75% believed that they already had a member of staff capable of doing these duties with some further training. PMID- 2923730 TI - Oral surgery: problems. AB - Having listened to, examined, tested, diagnosed and recommended a course of action to the patient, treatment will usually follow at the same or subsequent visits. In the vast majority of cases, the foregoing will have proceeded without a hitch, and the treatment completed to the satisfaction of both the practitioner and the patient. Years of study, and the acquisition of knowledge, skills and expertise, will have been condensed into a short amount of clinical time. Unfortunately, this highly desirable state of affairs cannot apply every time; problems can arise anywhere along the pathway leading to the successful completion of treatment. Some patients will present difficulties in diagnosis and treatment planning, whereas others will have problems either during the execution of treatment or post-operatively. Whenever a difficulty arises, it is essential to identify the problem, reappraise the situation and decide upon an appropriate course of action; flexibility is the key to success! In this article, three difficult areas are looked at: the fractured root, the use of antibiotics and the swollen face. PMID- 2923731 TI - Significance tests. AB - Simple methods of determining whether the difference between a sample mean and a given standard value is likely to be due only to sampling error, or to be real and/or of practical importance, are described. The use of the null hypothesis and of standard normal deviates is discussed, and examples are provided to illustrate the points made. PMID- 2923732 TI - A sojourn in Sweden. AB - In recent years, there has been a brisk increase of interest in disorders of the temporomandibular joint. Much valuable and pioneering research has been carried out in Scandinavia, particularly in Sweden. This article describes some impressions I formed of the Swedish Dental Service, and the way in which care for TM joint patients is managed in Sweden, during a visit I was able to make there. PMID- 2923733 TI - Lesions of skull base observed on high resolution computed tomography. A comparison with magnetic resonance imaging. AB - Forty patients with tumors involving the skull base were selected on the basis of findings at high resolution computed tomography (CT). The reliability of demonstrating bony lesions with magnetic resonance imaging (MRI) and CT were compared. CT showed osseous lesions of the skull base better than MRI but was less sensitive in evaluating an associated inflammatory reaction or in defining intracerebral infiltration. Small cortical lesions were only demonstrable with CT. MRI was superior in defining the full extent of soft tissue infiltration. Arterial encasement was observed at MRI. The special advantage of Gd-DTPA lies in the additional possibility to differentiate vessels from tumor-like lesions and in en plaque tumors. PMID- 2923734 TI - Atlantoaxial subluxation. Radiography and magnetic resonance imaging correlated to myelopathy. AB - Twenty-nine patients with atlantoaxial subluxation (18 with rheumatoid arthritis, 2 due to trauma, 4 with os odontoideum, and one each with polyarteritis nodosa, rheumatic fever. Klippel-Feil syndrome, achondroplasia, and cause unknown) were evaluated using a 0.22 tesla resistive MRI unit. Cord compression was classified into four grades according to the degree on magnetic resonance imaging. There were 7 patients with no thecal sac compression (grade 0). 10 with a minimal degree of subarachnoid space compression without cord compression (grade 1), 7 with mild cord compression (grade 2), and 5 with severe cord compression or cord atrophy (grade 3). Although the severity of myelopathy showed poor correlation with the atlantodental interval on conventional radiography, high correlation was observed between MR grading and the degree of myelopathy. The high signal intensity foci were observed in 7 of 12 patients with cord compression (grades 2 and 3) on T2 weighted images. Other frequently observed findings in rheumatoid arthritis included soft tissue masses of low to intermediate signal intensity in the paraodontoid space, erosions of the odontoid processes, and atlantoaxial impaction on T1 and T2 weighted images. PMID- 2923735 TI - Coil selection for magnetic resonance imaging of the cervical and thoracic spine using a vertical magnetic field. AB - In order to optimize the coil selection for cervical and thoracic spine imaging the signal characteristics of two different solenoidal surface coils (15 cm and 30 cm diameter, respectively) as well as the head coil and body coil were determined using a 0.3 T MR scanner with a vertical magnetic field. Signal-to noise ratio curves were obtained for each coil using tube phantoms and a human like phantom. The findings were compared with images obtained in two healthy volunteers. The head coil was found to be superior for imaging of the cranio cervical junction while the 15 cm surface coil gave better results in the remaining part of the cervical spine and the upper thoracic spine. The body coil was superior for imaging of the thoracic region at the level of the shoulders (T4 T6) but the 30 cm surface coil was better for the more caudal part of the thoracic spine. Combined phantom and in vivo studies are also recommended for evaluation of future, improved coils. PMID- 2923736 TI - Reproducibility of the pettersson scoring system. An interobserver study. AB - By means of the Pettersson scoring system, the degree of severity of haemophilic arthropathy in 128 knee, elbow and ankle joints was estimated by 5 radiologists. Their scores varied on average by approximately 3 points. Minimal and maximal joint involvement were scored consistently; exclusion of haemophilic arthropathy was possible with the highest degree of certainty. With regard to changes of a moderate degree agreement was seldom reached. With precisely defined characteristics, a high degree of consistency between observers was evident. Interobserver variation in the scoring was more marked in the ankle joint than in the other joints. Scoring was more consistent with the more experienced observers. PMID- 2923737 TI - In vivo evaluation of femoral blood flow measured with magnetic resonance. AB - Quantitative measurements of blood flow based on magnetic resonance imaging (MRI) using conventional multiple spin echo sequences were evaluated in vivo in healthy young volunteers. Blood flow was measured using MRI in the femoral vein. The initial slope of the multiple spin echo decay curve, corrected for the T2 decay of non-flowing blood was used to calculate the blood flow. As a reference, the blood flow in the femoral artery was measured simultaneously with an invasive indicator dilution technique. T2 of non-flowing blood was measured in vivo in popliteal veins during regional circulatory arrest. The mean T2 of non-flowing blood was found to be 105 +/- 31 ms. The femoral blood flow ranged between 0 and 643 ml/min measured with MRI and between 280 and 531 ml/min measured by the indicator dilution technique. There was thus poor agreement between the two methods. The results indicate that in vivo blood flow measurements made with MRI based on wash-out effects, commonly used in multiple spin echo imaging, do not give reliable absolute values for blood flow in the femoral artery or vein. PMID- 2923738 TI - Diagnosis of deep venous thrombosis of the leg using immunoscintigraphy with 111In-labelled monoclonal antifibrin antibody fragments. AB - Fourteen unselected consecutive patients with clinically suggested deep venous thrombosis were studied using 111In-labelled monoclonal antibody Fab-fragments (59D8) in order to evaluate the accuracy of antifibrin imaging. Scintigrams of the legs were obtained at 1 to 4 h and 20 to 28 h in all patients and in seven dynamic studies were also performed. Contrast medium phlebography used as diagnostic standard revealed thrombosis in six patients who also had increased uptake of the tracer at immunoscintigraphy. Three patients had a positive finding at immunoscintigraphy without thrombosis. Because of the high sensitivity of this method, normal antifibrin images may be used to exclude thrombosis. Phlebography may then be restricted to positive cases to confirm the presence of thrombosis. PMID- 2923739 TI - Problems in radiographic detection and diagnosis of lung cancer. AB - All chest radiographs of 107 proven lung cancer patients who received consecutive biennial chest radiography were reviewed to elucidate problems detecting their cancers, and diagnosing them when initially radiographically detected. Subjects, members of a fixed population sample, originally numbered 20,000 persons, 17,000 of whom consistently received consecutive biennial chest radiography during examinations for late effects of atomic-bomb radiation. Among the 107 subjects, 64 had radiographic manifestations of cancer; 47 were initially correctly diagnosed; 17 were not. Eleven of the 17 were initially equivocal, diagnosable only after subsequent radiography and retrospective review of serial radiographs. Diagnostic problems consisted of 1) six detection errors with cancer images superimposed on musculoskeletal and cardiovascular structures, reducible by stereoscopic p.a. instead of single p.a. radiography; immediate tentative interpretations; and by comparing earlier with current radiographs. 2) Eight decision errors, wherein cancers mimicked other diseases, were reducible by greater index of suspicion and scrutiny during interpretations. PMID- 2923740 TI - Computed tomography and mediastinoscopy in the assessment of resectability of lung cancer. AB - In order to assess the potential of computed tomography (CT) of the mediastinum and mediastinoscopy in the staging of lung cancer, 125 patients were examined. Of these, 104 underwent thoracotomy, at which there was no evidence of mediastinal tumour involvement in 79 while 25 patients had signs of tumour spread. The sensitivity and specificity of CT were 87.0 per cent and 95.8 per cent, respectively, in the detection of direct tumour extension with a mediastinal mass. When lymph node enlargement was the sole finding, CT did not provide any differentiation between benign and malignant lymphadenopathy. The mediastinal involvement was inaccessible on mediastinoscopy in 18 cases (72%). Despite the surperior sensitivity of CT it was often difficult to determine whether direct tumour infiltration of mediastinal structures had occurred. It was concluded that CT is necessary for screening the entire mediastinum and, when it reveals no evidence of mediastinal tumour spread, mediastinoscopy will yield no further information. Mediastinoscopy will help to correctly identify accessible mediastinal lymph node involvement of the superior mediastinum and to define the mediastinal tumour invasion in doubtful cases. PMID- 2923741 TI - Computed tomography reveals atypical localization of benign mediastinal tumors. AB - Computed tomographic appearances of 147 surgically proven mediastinal tumors (113 benign and 34 malignant lesions) were evaluated paying special attention to their localization or extension. Ten of the 113 benign lesions (9%) showed atypical or unique localization or extension, and were divided into three groups. In the first group, two lymphangiomas and one bronchogenic cyst spread over both the precardiovascular and the retrocardiovascular compartments, mimicking a malignant lesion. In the second group, the single cases of thymic hypertrophy, thymic cyst, schwannoma, and pericardial cyst were located atypically in the retrocardiovascular compartment. In the last group, two esophageal leiomyomas and one esophageal duplication showed upward and downward longitudinal extension beyond the azygos arch and the aortic arch. PMID- 2923742 TI - Spontaneous pneumothorax caused by metastatic hemangioendothelioma. Radiographic appearance and pathologic correlation. AB - A patient with hemangioendothelioma is described, who developed a metastatic pulmonary nodule, subsequently a bullous lesion contiguous to the nodule, and finally spontaneous pneumothorax. In such cases, newly formed bullous lesions may conceal originally visible metastatic foci and can be a potential source of spontaneous pneumothorax. PMID- 2923743 TI - Peristalsis in pharyngeal constrictor musculature in relation to positioning and gravity. AB - The motor activity of the pharyngeal constrictors in terms of peristalsis and protrusion depths was studied cineradiographically in 15 non-dysphagic volunteers in three positions: sitting, right decubitus horizontal, and head-down 30 degrees, during swallowing of a 10 ml bolus of thin liquid barium. Using a frame rate of 50/s the speed of peristalsis was calculated by frame counting. The speed of peristalsis and the depth of protrusion of the constrictor wall did not depend on the direction of gravity force in relation to the long axis of the pharynx. Neither the position of the hyoid bone nor its movement during pharyngeal swallowing changed in relation to position and gravity. Pharyngeal activity during swallowing in normal individuals is fairly stable and does not change in relation to gravity. PMID- 2923744 TI - Radiologic diagnosis of gastro-oesophageal reflux. AB - In 149 patients, a standardized radiologic method for the detection of gastro oesophageal reflux was applied and compared with the results obtained at endoscopy and by a manometric reflux test. Radiologic reflux was recorded in 53 patients, of whom 25 had reflux without abdominal compression and 51 with compression. At least one of the other two types of examination disclosed pathologic conditions in all but 2 of 53 patients. Oesophagitis was significantly more severe among the patients with reflux observed at radiography. The presence of hiatal incompetence with reflux only to the hiatal hernia but not to the oesophagus was not a strong indicator of gastro-oesophageal reflux disease. Hiatal hernia was present in a significantly larger number of the patients with reflux at radiography than in those without reflux. Increased width of the hiatus gave stronger evidence for reflux disease than in patients with a normal hiatus. Thus, the width of the hiatus also had a bearing on the diagnosis of gastro oesophageal reflux disease. PMID- 2923746 TI - Radiation dose to patients and personnel during fluoroscopy at percutaneous renal stone extraction. AB - The radiation dose to patients and personnel was estimated during 11 percutaneous renal stone extractions. For the patients the energy imparted, the mean absorbed dose to various organs, and the effective dose equivalent were estimated. For different personnel categories some organ doses and the effective dose equivalent were also estimated. Large differences in the radiation dose between patients were observed. The mean effective dose equivalent to the patient was 4.2 (range 0.6-8.3) mSv, and the energy imparted 285 (range 50-500) mJ. These figures are comparable to those reported for routine colon examination and urography. For the personnel there were also large differences between individuals and categories. The highest radiation dose was received by the radiologist. It was estimated that a radiologist who performs 150 percutaneous renal stone extractions per year will receive a yearly contribution to his/her effective dose equivalent of 2.4 mSv. Even when the contribution from other diagnostic and interventional radiologic procedures is added, the total effective dose equivalent hardly exceeds 5 mSv or 1/10 of the present dose limit for persons engaged in radiologic work. For the hands of the radiologist there is a risk of doses closer to the present limit for single organs or tissues of 500 mSv/year. PMID- 2923745 TI - Effect of superparamagnetic particles as oral contrast medium at magnetic resonance imaging. A phase I clinical study. AB - Non-biodegradable superparamagnetic particles were used as an oral contrast medium in different concentrations, and evaluated in 25 human volunteers. The aim of the study was to determine the most appropriate concentration of the contrast medium, and to evaluate the effect, distribution, safety and tolerance. With the concentration of 1.0 g/l a substantial reduction of the signal intensity in the bowel was achieved in both T1 and T2 weighted images. The intraabdominal structures were well differentiated from the bowels containing contrast medium. 'Metal' artifacts and blurring of adjacent structures, probably due to an increased local concentration, were observed at higher dosages. The distribution of the preparation in the gastrointestinal tract varied between individuals. As a rule a good contrast effect was achieved in the small bowel with the exception of the duodenum. The contrast medium was well accepted and did not cause any side effects of clinical importance. The results suggest that the preparation is well tolerated by humans and may be a useful contrast medium for abdominal MR imaging. PMID- 2923747 TI - Acute lethality after enteral administration of contrast media in anaesthetized rats with intestinal ischaemia. AB - The acute lethality was evaluated during enteric follow-through in anaesthetized rats with a ligature applied to the anterior mesenteric artery and vein. In 121 animals 3 ml of either sodium diatrizoate, iohexol or barium sulphate was administered via orogastric tube. Alternatively, they had the oro-gastric tube inserted but no test substance instilled (controls). A total of 103 rats was observed until spontaneous death while 18 were sacrificed after 8 hours of observation. The survival time in the sodium diatrizoate group was significantly shorter than for the other three groups (p less than 0.006). The 50% survival time was 5 h 42 min (range 2 h 48 min to 12 h 45 min) for sodium diatrizoate as compared with 8 h 4 min to 8 h 26 min for the other three groups; iohexol 8 h 4 min (range 2 h 4 min to 14 h 43 min), barium 8 h 13 min (range 4 h 55 min to 16 h 26 min) and no instilled substance 8 h 26 min (range 3 h 38 min to 16 h 10 min) with no significant differences between these 3 groups. The use of hyperosmolar contrast media in enteric follow-through significantly shortens the survival of rats with acute intestinal ischaemia. A more rapid spread of intestinal bacteria through the distended bowel wall and the ensuing septicaemia, accompanied by enhanced dehydration, are probably the mechanisms responsible for the earlier deaths. PMID- 2923748 TI - Nephropathy induced by intramuscularly administered glycerol and contrast media in rats. A comparison between diatrizoate, iohexol and ioxilan. AB - Urine profiles (albumin, glucose, NAG, LDH, GGT, sodium, and phosphate) were followed for 14 days after intravenous injection of either diatrizoate, iohexol, ioxilan, or saline in 24 Wistar rats with a glomerular and tubular dysfunction induced by intramuscularly (i.m.) administered glycerol. Another 6 rats exposed to neither glycerol nor contrast media served as controls. The effect of ioxilan and saline on the albumin excretion was similar, whereas diatrizoate and iohexol increased it significantly. The contrast media had no further inhibitory effect on the reabsorption of glucose. Iohexol caused significantly increased excretion of all three enzymes, ioxilan of NAG and LDH, whereas diatrizoate only increased the excretion of LDH. The sodium excretion was further increased by ioxilan and diatrizoate, whereas none of the contrast media affected the phosphaturia. Both ioxilan and iohexol caused a round cell response around the tubules shown by light microscopy whereas diatrizoate caused no further changes. It is concluded that diatrizoate and iohexol increase glomerular dysfunction induced by glycerol i.m.; all three contrast media cause some further increase in the tubular dysfunction. Neither diatrizoate, iohexol nor ioxilan prolong nephropathy induced by glycerol i.m. determined by the chemical analyses. The histologic finding indicates a direct toxic effect of non-ionic low osmolar contrast media in this animal model of nephropathy. PMID- 2923749 TI - Preoperative needle-marking of non-palpable breast lesions. PMID- 2923750 TI - Relation of third and fourth heart sounds to blood velocity during left ventricular filling. AB - To investigate the relation between changes in left ventricular inflow velocity and the timing of third and fourth heart sounds, simultaneous phonocardiograms and continuous wave Doppler traces were recorded in 48 patients (aged 17-78) with heart disease and in 21 normal children. The onset of the first vibration of the third heart sound coincided with peak left ventricular inflow blood velocity to within 5 ms in all but two of the patients. The mean (SD) difference between the two events was 5 (5) ms, which did not differ significantly from zero. The relation was similar in patients with primary myocardial disease (11), and in those with valve disease (26), hypertension (five), and coronary artery disease (four). In the normal children, the mean interval was 2.5 (5) ms--not significantly different from zero. By contrast, the first deflection of the fourth heart sound consistently preceded the timing of peak atrial inflow velocity by 55 (10) ms. Agreement was much closer between the onset of atrial flow and the onset of the atrial sound (mean difference 1 (5) ms, not significantly different from zero). Gallop sounds seem to be closely related to changes in ventricular inflow velocity, and thus to the effects of forces acting on blood flow. The forces underlying the third sound seem to arise within the ventricle and are responsible for sudden deceleration of flow during rapid ventricular filling. The fourth sound, occurring at the onset of the "a" wave, is more likely to arise from dissipation of forces causing acceleration of blood flow--that is, atrial systole itself. PMID- 2923751 TI - Impaired blood pressure response to exercise in patients with coronary artery disease: possible contribution of attenuated reflex vasoconstriction in non exercising muscles. AB - Eighteen patients with coronary artery disease were divided into two groups according to whether their blood pressure decreased (eight, group 1) or increased (10, group 2) in response to treadmill exercise testing. Age and the extent and distribution of coronary artery disease were similar in the two groups. At rest, blood pressure, pulmonary artery wedge pressure, cardiac index, forearm vascular resistance, and oxygen consumption were similar in the two groups. During supine leg exercise on a bicycle ergometer mean blood pressure increased in group 2 but did not change in group 1. Increases in cardiac index, pulmonary artery wedge pressure, and oxygen consumption during leg exercise were not significantly different in the two groups but forearm vascular resistance increased less in group 1 than in group 2. There was a positive correlation between the magnitude of the change in mean blood pressure and change in forearm vascular resistance during leg exercise. The impaired response of blood pressure to leg exercise in group 1 was not the result of a failure of the cardiac index to increase. The results suggest the possibility that attenuation of reflex vasoconstriction in non-exercising muscles may contribute to the impaired response of blood pressure to exercise in patients with coronary artery disease. PMID- 2923752 TI - Electrocardiographic findings in male veteran endurance athletes. AB - Twenty male veteran endurance runners and 20 controls underwent resting, exercise, and ambulatory electrocardiography. Four athletes and three controls satisfied voltage criteria for left ventricular hypertrophy. The PR interval was longer in the athletes and they had longer mean (SD) treadmill exercise times (19 (4) v 16 (2) min) than the controls. Four athletes but no controls had greater than 2 mm downsloping ST segment depression during exercise. During 48 hour ambulatory electrocardiography the athletes had a consistently lower heart rate but maintained a circadian variation. Profound bradycardia (less than 35 beats/min) occurred in eight athletes but only one control. Eight athletes and two controls had asystolic pauses ranging from 1.8 to 15 seconds. Six athletes had first degree heart block, four had Mobitz II second degree block, and three had complete heart block. Most conduction abnormalities occurred at night and resolved during exercise. Ventricular ectopic activity was not significantly different between the groups. Thus heart block patterns and profound bradycardia are more frequent in older athletes than their youthful counterparts. PMID- 2923753 TI - Optimal atrioventricular delay at rest and during exercise in patients with dual chamber pacemakers: a non-invasive assessment by continuous wave Doppler. AB - The optimal atrioventricular delay at rest and during exercise was investigated in nine patients with heart block and implanted dual chamber pacemakers. All patients studied had normal left ventricular function and a normal sinus node rate response to exercise. Cardiac output was measured by continuous wave Doppler and was calculated as the product of stroke distance measured by Doppler at the left ventricular outflow, aortic root area measured by M mode echocardiography, and heart rate. Pacemakers were programmed in the DDD mode. Cardiac output was measured with the patient at rest while supine and while erect and at the peak of submaximal exercise (the end of stage 1 of the Bruce protocol) with the pacemakers programmed to the following atrioventricular intervals: 75-80 ms, 100 110 ms, 140-150 ms, and 200 ms. During exercise the basic pacing rate was programmed to 70 beats/min. Cardiac output at rest while supine and erect was greatest with an atrioventricular delay of 140-150 ms and it was significantly higher than that with an atrioventricular delay of 75-80 ms. On average there was a 31% decrease in cardiac output when patients stood up. During treadmill exercise, however, cardiac output was greatest when the atrioventricular delay was 75-80 ms, and this was significantly higher than the cardiac output with atrioventricular delays of 150 and 200 ms. During exercise 1:1 atrioventricular relations were maintained in patients at all atrioventricular intervals. In patients with atrioventricular sequential pacemakers cardiac output at rest is greatest with an atrioventricular delay of 140-150 ms but during exercise the optimal atrioventricular delay is shorter. Rate modulation of the atrioventricular interval may improve the haemodynamic response and possibly exercise tolerance in patients with dual chamber pacemakers. PMID- 2923754 TI - Determination of the ratio of pulmonary blood flow to systemic blood flow by derivation of amplitude weighted mean velocity from continuous wave Doppler spectra. AB - Conventional Doppler echocardiographic techniques for the estimation of blood flow ratios depend on the precise measurement of the diameters of the aorta and the pulmonary artery and the mean blood flow velocities in these vessels. A simpler and quicker method is described, based on the calculation of the systolic time integrals of the amplitude weighted mean velocities from continuous wave Doppler spectra within the great arteries. In 30 controls the mean (2 SD) ratio of pulmonary to systemic blood flow averaged 0.952 (0.085). The results of the new technique showed a good agreement with those of quantitative dye dilution and oximetry in 16 patients with intracardiac left to right shunts. PMID- 2923755 TI - Unemployment, socioenvironmental factors, and coronary heart disease in Scotland. AB - Scotland, which has one of the highest death rates in the world from coronary heart disease, also has considerable regional variation in mortality from this cause. The relation between standardised mortality ratios for coronary deaths (1979-83) for 56 local government districts and a range of socioeconomic factors from the 1981 Census as well as climatic factors and water hardness were investigated. Strong associations were seen with several measures of social disadvantage, the strongest being with percentage of male unemployment. A fitted multiple regression model with mortality from coronary heart disease in men found independent effects of two social variables (percentage male unemployment and percentage social class III-V) and one climatic factor (rainfall). The model explained much (73%) of the geographical variation in mortality from coronary heart disease, but part of the geographical pattern, in particular some of the east-west gradient in mortality, remained unexplained by it. Explanations for the geographical variation and the association with economic factors are currently being sought in terms of individual risk factors in a large screening study, the Scottish Heart Health Study. PMID- 2923756 TI - Clinical sustained uniform ventricular tachycardia in hypertrophic cardiomyopathy: association with left ventricular apical aneurysm. AB - Of 51 patients with hypertrophic cardiomyopathy who had episodes of ventricular tachycardia detected during ambulatory electrocardiographic monitoring only two had clinical sustained uniform ventricular tachycardia that required medical treatment because of worsening symptoms. In both patients the arrhythmia was associated with the uncommon finding of an apical aneurysm with angiographically normal coronary arteries. PMID- 2923757 TI - Determination of left ventricular volumes by Simpson's rule in infants and children with congenital heart disease. AB - Regression equations were developed from left ventricular casts of known volumes to calculate left ventricular volumes from biplane cineangiography obtained in non-standard views. Volumes were calculated by Simpson's rule from casts of postmortem specimens from patients with congenital heart disease. The casts were divided into two groups: those that came from patients with abnormal right ventricular haemodynamic function (group 1, n = 11) and those that came from patients in which it was normal (group 2, n = 9). Biplane cinegrams were taken in conventional (anteroposterior/lateral, right anterior oblique/left anterior oblique) and non-conventional (long axis oblique, hepatoclavicular, and sitting up) projections. The true volume of each cast was determined from its weight and specific gravity. Correlations between measured and true volumes (r = 0.96 to 0.99) were excellent in all projections, although each projection overestimated the true volumes (slope = 0.72 to 0.94). The regression equations obtained from conventional views were significantly different from those from the non conventional views; however, the regression slopes in group 1 were not different from those in group 2 in any view. Regression equations obtained by Simpson's rule do not seem to be affected by the haemodynamic state of the right ventricle. Different regression equations are required to measure left ventricular volumes from non-conventional angiograms. PMID- 2923758 TI - Balloon dilatation of the aortic valve for congenital aortic stenosis in childhood. AB - Balloon dilatation of the aortic valve was attempted in 34 consecutive children aged 16 months to 17 years (median 7 years), weight range 9-60 (median 22) kg. Previous surgical valvotomy had been performed in two patients (twice in one of them). The valve was not crossed in one patient. In the remaining 33 patients the pressure difference between the left ventricle and the ascending aorta during systole was reduced from 71 (30) to 28 (19) mm Hg. In 24 patients recatheterisation 2-19 (mean 9) months later showed gradients that were similar to those immediately after balloon dilatation (35 (20) v 31 (20) mm Hg). The two patients with the highest residual gradients immediately after balloon dilatation showed a spontaneous reduction in gradient at repeat catheterisation, whereas the patient who had twice had previous surgical valvotomy showed an increase in gradient from 37 to 99 mm Hg over nine months and required aortic root replacement. Balloon dilatation was repeated in two patients and this caused a further reduction in gradient. New aortic regurgitation occurred in nine (27%) patients (grade I, 8; grade II, 1) and aortic regurgitation was exacerbated (grade I to II) in two of the nine with pre-existing aortic regurgitation. External iliac artery avulsion occurred in one (3%) patient and two (6%) required intravenous streptokinase because the femoral artery became occluded. There were no other complications. Open valvotomy was performed in the child in whom the valve was not crossed, but no other child required aortic valve operation. Balloon dilatation of the aortic valve gave reasonable short term palliation and was well tolerated. It is an alternative to surgical valvotomy for initial palliation of congenital aortic stenosis in many children. PMID- 2923759 TI - Distinguishing between anomalous origin of the left coronary artery from the pulmonary trunk and dilated cardiomyopathy: role of echocardiographic measurement of the right coronary artery diameter. AB - Patients with anomalous origin of the left coronary artery from the pulmonary trunk usually have a large right coronary artery. This study examines the diagnostic value of measuring the diameter of the right coronary artery by echocardiography in distinguishing between this lesion and other causes of dilated cardiomyopathy. The diameter of the right coronary artery and the right coronary artery/aorta ratio were measured in the parasternal short axis view in 40 controls, 11 patients with dilated cardiomyopathy, and 10 with anomalous origin of the left coronary artery from the pulmonary trunk. In the controls, the diameter of the right coronary artery increased with age, but the right coronary artery/aorta ratio remained constant. In the control group the 95% upper limits of prediction for right coronary artery diameter were 1.6 mm for one month of age, 1.8 mm for three months, 2.0 mm for one year, 2.2 mm for two years, 2.4 mm for three years, 2.6 mm for four years, 2.7 mm for six years, 3.0 mm for eight years, and 3.2 mm for 10 years; and for right coronary/aorta ratios the limits were 0.17 for one month to one year, 0.18 for one to six years, 0.19 for six to 10 years, and 0.20 for more than 10 years. All patients with dilated cardiomyopathy had normal right coronary artery diameters and right coronary artery/aorta ratios (0.10-0.13). Those patients with anomalous origin of the left coronary artery from the pulmonary trunk had larger than normal right coronary artery diameter and a significant increase in the right coronary artery/aorta ratio (0.21-0.29). The presence of an anomalous left coronary artery was likely if the diameter of the right coronary artery or the right coronary artery/aorta ratio was larger than the normal 95% limits of prediction. PMID- 2923760 TI - Impaired left ventricular diastolic filling in patients with familial amyloid polyneuropathy: a pulsed Doppler echocardiographic study. AB - To assess left ventricular diastolic filling in patients with amyloid heart disease 12 patients with familial amyloid polyneuropathy and 15 normal subjects were studied by pulsed Doppler echocardiography. None of the patients had clinical evidence of overt heart disease or restrictive cardiomyopathy and only two of them showed ventricular wall thickening. The peak flow velocity of rapid diastolic filling and the acceleration rate of early diastolic inflow were significantly lower in patients with familial amyloid polyneuropathy than in controls. The pressure half time was significantly longer in patients than in controls. In addition, the peak flow velocity during atrial contraction and the ratio of atrial peak flow velocity to rapid diastolic peak flow velocity were significantly greater in patients than in controls. Although there were no significant correlations between measurements of diastolic filling and clinical findings in patients with familial amyloid polyneuropathy, the ratio of atrial peak flow velocity to rapid diastolic peak flow velocity was significantly related to left ventricular posterior wall thickness. These findings suggest that in patients with cardiac amyloidosis without restrictive cardiomyopathy, abnormal left ventricular diastolic filling, manifested by a reduction in the rate and volume of rapid diastolic filling with enhanced atrial contraction, can be seen even in the early stage of the disease. PMID- 2923761 TI - Familial aortic dissection: a report of rare family cluster. AB - Acute aortic dissection occurred in three of four siblings without Marfan syndrome. All of them were successfully treated by operation and remain well 6-42 months after operation. Their mother died suddenly in another hospital of acute aortic dissection. All her siblings were dead and cardiovascular disease was suspected in all of them. PMID- 2923762 TI - Correcting a block? Successful experience of a small British pacing centre. PMID- 2923763 TI - Effects on the lower oesophageal sphincter of cisapride given before the combined administration of atropine and neostigmine. AB - Twenty healthy female patients undergoing laparoscopy were allocated randomly to receive either cisapride 10 mg i.v. in 5% dextrose 20 ml or placebo 15 min before antagonism of residual neuromuscular blockade with atropine 1.2 mg and neostigmine 2.5 mg. Barrier pressure (BrP = lower oesophageal sphincter (LOS) pressure minus gastric pressure) increased significantly (by 25%) following cisapride, but not placebo, within 10 min of injection; following the combined administration of atropine and neostigmine, there was an abrupt decrease in mean BrP in the cisapride group from 37.0 (SEM 4.5) cm H2O to 24.1 (3.2) cm H2O (P less than 0.01) and in the control group from 26.6 (4.8) cm H2O to 19.9 (3.1) cm H2O (P less than 0.05) 2 min after injection. Subsequently, there was a small increase in BrP to values not significantly lower than control measurements. Thus the administration of cisapride before antagonism of neuromuscular blockade with atropine and neostigmine failed to block the adverse effect of atropine on the LOS. PMID- 2923764 TI - Effects of general anaesthesia with halothane on antroduodenal motility, pH and gastric emptying rate in man. AB - Antroduodenal motility, pH and gastric emptying rate were measured in 11 patients undergoing orthopaedic or plastic surgery with general anaesthesia. Motility was measured by manometry and gastric emptying rate by the rate of paracetamol absorption. During anaesthesia, gastric emptying was delayed in eight patients. General anaesthesia with halothane reduced the duration of the interdigestive motility complex (P less than 0.01), mainly by a shortening of phase II (P less than 0.01) which correlated with the inhaled concentrations of halothane (P less than 0.01). Anaesthesia impeded the occurrence of antral contractions during phase II (P less than 0.01); the frequency of contractions was unchanged during anaesthesia, but decreased during the recovery period (P less than 0.01). The amplitudes of antral contractions diminished with anaesthesia (P less than 0.01), but increased after operation. The frequency of contractions in the duodenum was unchanged during phase II and reduced during phase III (P less than 0.01). Gastric pH increased during and after operation (P less than 0.01). General anaesthesia with halothane affects gastroduodenal motility especially during phase II, increases gastric pH and delays gastric emptying rate. PMID- 2923765 TI - Comparison of 1.5% enflurane with 1.25% isoflurane in oxygen for caesarean section: avoidance of awareness without nitrous oxide. AB - We examined the feasibility of administering nearly 100% oxygen throughout the induction-delivery period of general anaesthesia for 113 Caesarean sections. Isoflurane 1.25% was compared with 1.5% enflurane for maintenance of anaesthesia. The level of anaesthesia was monitored by use of the isolated forearm technique. There was a greater amount of isolated forearm movement when enflurane was used. The three main criteria for a satisfactory general anaesthetic technique for Caesarean section were fulfilled, namely no maternal awareness, no undue depression of the fetus and no adverse effect on uterine contractility. Isoflurane and enflurane appear to be suitable anaesthetic agents for facilitating hyperoxygenation during Caesarean section. PMID- 2923766 TI - Plain bupivacaine: 0.5% or 0.25% for spinal analgesia? AB - Plain 0.5% bupivacaine 3 ml was compared with plain 0.25% bupivacaine 6 ml for spinal anaesthesia during transurethral surgery in 40 patients. The solutions were injected over 30 s at the L3/4 space with the patient in the sitting position. The patient was kept sitting for 2 min, supine for 5 min and then placed in the lithotomy position. No significant differences were found in onset time, extent of cephalad spread, duration of sensory or motor blockade, or side effects. The use of a 0.5% plain solution of bupivacaine did not appear to confer any advantage over the 0.25% solution. PMID- 2923767 TI - Pharmacokinetics of atracurium and laudanosine in patients with hepatic cirrhosis. AB - The pharmacokinetic profiles of atracurium and one of its derivatives, laudanosine were studied following an i.v. bolus of atracurium 0.6 mg kg-1 administered to eight patients with hepatic cirrhosis and to seven healthy controls. The central volume of distribution of atracurium was greater in the patients with cirrhosis (104.6 ml kg-1) compared with the controls (69.6 ml kg-1) (P less than 0.05), as was the total volume of distribution (281.8 ml kg-1 and 202.1 ml kg-1, respectively) (P less than 0.05). There was no significant difference in the elimination half-life of atracurium between the two groups. The total volume of distribution of laudanosine was increased in cirrhotic patients (2.68 litre kg-1) (P less than 0.05), as was its elimination half-life (277 min in cirrhotic individuals; 168 min in controls) (P less than 0.05). There was no significant difference in the clearance of laudanosine between the two groups. PMID- 2923768 TI - Changes in oxygen saturation during inhalation induction of anaesthesia in children. AB - Changes in oxygen saturation (SaO2) were studied during induction of anaesthesia in 48 healthy children receiving halothane or isoflurane for outpatient dental extractions. Substantial reductions in SaO2 occurred in more than 50% of the children given isoflurane and were associated with the irritant effects of this agent on the airway. SaO2 was largely unaltered during the use of halothane. These findings indicate that the airway complications caused by isoflurane may be associated with decreases in SaO2. PMID- 2923769 TI - Comparison of continuous paravertebral and extradural infusions of bupivacaine for pain relief after thoracotomy. AB - Pain was controlled in 20 post-thoracotomy patients using a continuous infusion of 0.25% bupivacaine through an extradural or para-vertebral catheter. Both techniques provided good analgesia. Hypotension and urine retention occurred significantly less frequently in the paravertebral than in the extradural group. PMID- 2923770 TI - Oxygen desaturation following sedation for regional analgesia. AB - Moderate to severe arterial oxygen desaturation (SaO2 75-88%) occurred in three of four patients who were given sedation during regional conduction block without the administration of oxygen. No desaturation occurred in six patients given oxygen 2 litre min-1 via a nasal catheter during similar procedures. It is concluded that patients undergoing regional conduction block with concurrent sedation should receive additional oxygen routinely unless a pulse oximeter is available for monitoring. PMID- 2923771 TI - Pancuronium allergy: a case report. AB - A case of anaphylactic shock to pancuronium bromide is described in which a type I immunological reaction occurred. A 33-yr-old male anaesthetist, with no family or personal history of allergy, collapsed soon after induction of anaesthesia. The drugs used included fentanyl, droperidol, thiopentone and pancuronium. Diffuse erythema occurred, with probable cardiac arrest. The patient was treated with cardiac massage, sympathomimetics and cortisone, and made a complete recovery. Examination (skin tests, passive transfer according to Prausnitz and Kustner, in vitro lymphocyte transformation test, total IgE assay) revealed that the allergic reaction was to pancuronium bromide. PMID- 2923772 TI - Profound intraoperative atelectasis. AB - Severe intraoperative hypoxaemia occurred in a previously healthy 19-yr-old accident victim. Although rare, major lung collapse secondary to mucous plugging should be considered in the differential diagnosis of intraoperative hypoxaemia, particularly following major trauma. PMID- 2923773 TI - Proceedings of the Anaesthetic Research Society. London, November 11, 1988. Abstracts. PMID- 2923774 TI - Nasotracheal intubation, paranasal sinusitis and head injuries. PMID- 2923775 TI - Prolonged suxamethonium-induced neuromuscular block associated with organophosphate poisoning. PMID- 2923776 TI - Measurement of transdiaphragmatic pressure. PMID- 2923777 TI - Dos and don'ts of a code: dealing with cardiac arrest (continuing education credit). PMID- 2923778 TI - Do nurses need mandatory continuing education? AB - The impact of continuing education depends upon the willingness and readiness of nurses to implement change in their own practice by realizing that competence in any profession requires periodic updating. Nurses who describe themselves as professionals need to accept a personal responsibility for their own continued learning. PMID- 2923779 TI - Analyzing ADN competencies. AB - El Paso Community College District, using the DACUM Process, identified 19 major competency areas with 313 specific competencies for AD Nursing. This article provides an overview of the DACUM Process, a discussion of the application to the ADN program, a summary of the results, and future activities. PMID- 2923780 TI - Traveling nurse: one nurse's journey. PMID- 2923781 TI - Nursing diagnosis for patients with psychiatric problems. AB - Nursing diagnosis can be a useful tool in planning the care of the psychiatric patient, if the diagnostic label and etiology are developed accurately. Goals and interventions are planned to meet the defined nursing diagnoses. Examples of the application of the nursing process to the care of the mentally ill are described. PMID- 2923782 TI - Collision course. PMID- 2923784 TI - Toward tenure. PMID- 2923783 TI - Where the boys aren't. AB - Many causative factors have been cited for our present national nursing shortage. Some of these are: the "baby bust" of the late sixties and seventies, the women's movement, inadequate salaries, and shift work. Yes, an untapped pool of potential applicants exists--men. This article asks why nursing is "where the boys aren't." PMID- 2923785 TI - Diuretics. PMID- 2923786 TI - Legal aspects of a code. PMID- 2923787 TI - Connective tissue responses to some heavy metals. III. Silver and dietary supplements of ascorbic acid. Histology and ultrastructure. AB - Silver-loaded ion exchange resin beads implanted into loose connective tissue of the rat pinna produced a local reaction. Initially the lesion comprised local necrosis and tissue disruption with predominantly small round cell infiltration. The subsequent organization was delayed and disordered. Fibroblasts developed grossly dilated cisternae of the rough endoplasmic reticulum. The matrix contained poorly orientated collagen fibrils of varying size and ground substance appeared condensed and granular. Distorted collagen fibrils were identified within membrane-bound vacuoles in the cytoplasm of both fibroblasts and macrophages. Abnormalities of the silver lesion were indicative of disordered collagen biosynthesis. Silver interfered with the biosynthesis and assembly of matrix components of the connective tissue. The reaction to silver beads in rats maintained on a diet heavily supplemented with ascorbic acid approached that of the control (sodium-loaded bead) with respect to the time scale, tissue reaction and tissue organization. The collagen matrix which formed was more organized and of greater density than that in the rat maintained on a normal diet. However, the repair tissue retained some of the morphological features of the legacy of silver toxicity, in particular delayed repair and dense intracellular fibrils within fibroblasts and macrophages. The excess of ascorbic acid partially ameliorated the effect of silver, possibly by compensating catabolysis of ascorbic acid caused by the presence of the released silver. PMID- 2923788 TI - Experimental frost-bite in Hanford Miniature Swine. I. Epithelial changes. AB - Frost-bite lesions were produced in five Hanford Miniature Swine exposed to - 75 degrees C air for 1, 3, 5, 10 or 20 min. Biopsies were taken at 0, 3, 6, 12, 24 and 48 h and 1 and 2 weeks. Two hundred slides were evaluated microscopically: pyknosis, vacuolation, individualization of cells, and degeneration were graded from 0-5; 0, no change; 5, severe change. Necrosis, new epithelium, and microabscesses were recorded as present or absent. Early changes of vacuolation of keratinocytes, individualization of cells and pyknosis increased with biopsy time until 1 week, at which time more severe changes predominated. Intermediate changes of advanced degeneration and dermoepidermal microabscesses were seen at 48 h and 1 and 2 weeks. Late changes of necrosis and epithelial regeneration occurred, both separately or together in the same tissue, at 1 and 2 weeks. Regeneration occurred either as complete replacement of epithelium, or as crescents of new epithelium beneath degenerating epithelium. The results show that necrosis is a late development, so prognosis based on early skin biopsies must be guarded to unfavourable. Furthermore, these findings suggest that cold has a direct effect on epithelial cell membranes. PMID- 2923789 TI - Experimental frost-bite in Hanford Miniature Swine. II. Vascular changes. AB - Frost-bite lesions were produced in five Hanford Miniature Swine exposed to - 75 degrees C air for 1, 3, 5, 10, or 20 min. Biopsies were taken at 0, 3, 6, 12, 24, and 48 h, and 1 and 2 weeks. Two hundred slides were evaluated microscopically: superficial and deep hyperaemia, vascular inflammation, medial degeneration, and thrombosis were graded from 0 to 5; 0, no change; 5, severe change. Haemorrhage was recorded as present or absent. Hyperaemia was the earliest change seen, both grossly and microscopically. Leucocyte emigration and vasculitis were intermediate stages seen most commonly in the 6, 12, and 24 h biopsies. Medial degeneration and thrombosis, the most severe vascular changes, were not seen until 1-2 weeks following frost-bite injury. These findings show that the outcome of frost-bite can not be accurately predicted from early frost-bite lesions, because thrombosis and medial degeneration are not evident in early lesions. PMID- 2923790 TI - Tooth root resorption induced in rats by diphenylhydantoin and parathyroidectomy. AB - Changes in bone, cartilage and the dentition in animals and man following the administration of anticonvulsant drugs resemble those seen in hypoparathyroidism and pseudohypoparathyroidism. Groups of 21-day-old rats were treated with diphenylhydantoin, parathyroidectomized, or made hypocalcaemic with a calcium deficient diet. Histological examination revealed extensive resorption of cementum and dentine in the molars of the drug-treated and parathyroidectomized rats, but not in the hypocalcaemic or control groups. Localization of injected tetracycline by fluorescence showed that the resorption affected the distal side of the tooth roots and had occurred after root formation. No changes in cementum formation on the mesial side of the roots had occurred in any of the experimental groups. These results suggest that diphenylhydantoin induces a condition similar to pseudohypoparathyroidism in which the resistance of tooth roots to resorption is reduced. PMID- 2923791 TI - The effect of carbon tetrachloride on the copper-laden rat liver. AB - Copper is believed to be hepatotoxic in Indian Childhood Cirrhosis and Wilson's disease. However, copper-loading causes only minimal hepatic damage in animal models. The hypothesis was therefore proposed that a second hepatic insult may precipitate or perpetuate liver injury in a copper-laden liver. In non-copper dosed rats CCl4 (10 mmol/kg, i.p.) produced elevated serum AST (809 +/- 298 IU/l, normal 20 +/- 5) and ALT (295 +/- 157 IU/l, normal 6 +/- 1) and extensive liver cell necrosis, portal tract inflammation, fat deposition, and perilobular hepatocyte ballooning. In rats whose liver copper was elevated from 75 +/- 13 to 461 +/- 13 micrograms/g by oral copper supplementation, CCl4 produced much smaller increases in AST (492 +/- 80 IU/l) and ALT (172 +/- 57 IU/l) and mild focal liver cell necrosis. Fat deposition and perilobular vacuolation were not reduced. Prior copper-loading of rats unequivocally protected against the CCl4 induced liver injury. Triglyceride accumulation, however, was apparently unaffected. The possible interactions of copper with prostaglandin-mediated inflammation and with free-radical-induced liver damage are discussed. PMID- 2923792 TI - Benzo(a)pyrene metabolism, DNA-binding and UV-induced repair of DNA damage in cultured skin fibroblasts from a patient with unilateral multiple basal cell carcinoma. AB - The metabolism of benzo(a)pyrene (BP), a ubiquitous environmental carcinogen, and its subsequent binding to DNA, and the repair of UV-induced DNA damage were studied in fibroblasts cultured from the skin of a 61-year-old male who had multiple BCC (greater than 100) on his left upper trunk. Biopsies were obtained and fibroblasts cultured from clinically normal tumour-free skin adjacent to tumour-bearing sites (TBS) and from visibly uninvolved normal skin (UNS) at distant sites. The cultured cells were incubated with [3H]-BP for 24 h and BP metabolism was assessed by HPLC and the formation of BP-diols, quinones and phenols verified. Total BP metabolism was 45% lower in TBS fibroblasts than in UNS fibroblasts. The formation of BP-7,8-diol, the precursor of the carcinogenic end product of BP metabolism, was 53% lower in TBS cells than in UNS cells. Pretreatment of UNS cells with benz(a)anthracene (BA) (x 10(-4) M) did not significantly affect BP metabolite formation whereas BA-treatment of TBS cells resulted in 55% and 76% increases in total BP metabolism and BP-7,8-diol formation, respectively. Treatment of TBS cells with BA also caused a substantial increase (95%) in BP-DNA adduct formation. Whereas DNA-binding in UNS cells was unaffected by this treatment. In response to irradiation with 2J/m2 UVC, total DNA repair was similar in both cell types; on alkaline elution it appeared that the TBS cells were more efficient in repairing UV-induced DNA strand breaks. These results suggest that BP metabolism and repair of DNA are altered in TBS cells and that patients with this type of metabolic profile may be at higher risk of the development of cutaneous neoplasms. It is also possible that fibroblasts from tumour bearing skin undergo some as yet unexplained alteration in carcinogen metabolism as a consequence of the induction of neoplasia. PMID- 2923793 TI - Polymorphic light eruption: an immunopathological study of evolving lesions. AB - Polymorphic light eruption (PLE) papules were successfully induced on previously affected sites in 11 out of 14 patients with PLE 4-20 h after single exposures to suberythemogenic doses of solar simulated radiation. Histological examination of biopsies performed 1 h, 5 h, 24 h, 72 h and 144 h post-irradiation revealed onset within 5 h of perivascular cellular infiltration. The infiltrate was dominated by lymphocytes in both early and established lesions, without evident epidermal pathology. Immunohistochemistry demonstrated a predominance of CD4+ cells in lesions up to 72 h post-induction, but later biopsies were dominated by a CD8+ infiltrate. Significantly increased numbers of dermal macrophages and CD1b+ cells were detected 1 h and 5 h post-irradiation, respectively. These findings are consistent with a delayed type hypersensitivity response underlying the pathogenesis of polymorphic light eruption. PMID- 2923794 TI - The spectrum of livedo reticularis and anticardiolipin antibodies. AB - We document a study of 65 patients presenting to our clinics, over a 2-year period, with livedo reticularis. All patients were screened for the presence of anti-cardiolipin antibodies and assessed for the presence of central nervous system disease and features of the 'antiphospholipid' syndrome, including venous and arterial thromboses and foetal loss. Patients were also assessed for other clinical features such as Raynaud's phenomenon and valvular lesions. Twenty-eight anti-cardiolipin positive patients were compared with 37 anti-cardiolipin negative patients. There was a statistically significant difference in the incidence of cerebrovascular disease (including strokes and transient ischaemic attacks) thrombocytopenia, valvular heart lesions and foetal loss in the anti cardiolipin positive patients as compared with the anticardiolipin negative groups. PMID- 2923795 TI - A quantitative assessment of Langerhans cells in oral mucosal lichen planus and leukoplakia. AB - Quantitative analysis of Langerhans cells stained with OKT6 in the epithelium of 42 patients with oral mucosal lichen planus and 14 patients with oral mucosal leukoplakia showed significantly greater numbers of Langerhans cells in lichen planus. This may reflect the role of Langerhans cells in the pathogenesis of this condition and their identification could help in distinguishing lichen planus from leukoplakia. PMID- 2923796 TI - Exogenous ochronosis: an epidemiological study. AB - A survey was conducted to investigate the relationship between exogenous ochronosis and the use of skin lightening preparations amongst black individuals attending general outpatient departments in two South African hospitals. In the sample, 15% of males and 42% of females were found to have exogenous ochronosis. The prevalence amongst users of skin lighteners was 69%. The main demographic associations with ochronosis were an inverse relationship to education, and predominance of the female sex. Clinical and behavioural aspects were also recorded. Even products limited to 2% hydroquinone or less, and combined with a sunscreen, were found to cause ochronosis. PMID- 2923797 TI - Atopic dermatitis and house dust mites. AB - The occurrence of house dust mites (Dermatophagoides spp) was investigated in the homes of 26 patients with atopic dermatitis (AD), 20 patients with psoriasis and 41 randomly selected homes in Arhus, Denmark. The AD patients with moderate to severe eczema had an increased concentration of mites (median 85 mites/0.1 g mattress dust) compared with the controls (median 8 mites/0.1 g mattress dust). The higher exposure to house dust mites corresponded to a relative risk of 4.6 and a clear dose-response relationship between exposure and disease could be demonstrated. Our results illustrate a clear association between moderate to severe atopic dermatitis and increased exposure to house dust mites in the patients' homes, and support the hypothesis that mite antigens could be an aetiological factor in atopic dermatitis. PMID- 2923799 TI - British Society for Investigative Dermatology, annual meeting. Manchester, September 1988. Abstracts. PMID- 2923798 TI - Long-term cyclosporin for psoriasis. AB - Thirteen patients with severe persistent psoriasis, intolerant of, or unresponsive to, other current treatments have been treated with cyclosporin (Cys) for periods varying from 12-25 (mean 18) months. The dose ranged from 1-4 mg/kg/day (mean 2.8 mg). There was a 72% reduction in the mean PASI score at 4 weeks, and at the end of the study, an 81% reduction. Adjuvant therapy with topical steroids was used in 11 of the 13 patients after the first 3 months of Cys treatment to persistent patches on an intermittent basis with beneficial effect. Six patients developed mild to moderate hypertension, in three this was controlled by a reduction in the dose of Cys, and in the other three by hypotensive agents. The mean serum creatinine rose from 72 to 90 microM/l during the study. Hypertrichosis occurred in seven of the 13 patients. Low dosage Cys is an effective treatment for clearing psoriasis and maintaining improvement on a long-term basis. PMID- 2923800 TI - Reversible gynaecomastia associated with etritinate. PMID- 2923801 TI - Meyerson's naevi in pityriasis rosea. PMID- 2923802 TI - Platelet hyperaggregability in two patients with Klinefelter's syndrome complicated by leg ulcers. PMID- 2923803 TI - The natural history of 'dystrophic' pili torti. PMID- 2923804 TI - In vivo and in vitro inhibitory effect of alpha-interferon on megakaryocyte colony growth in essential thrombocythaemia. AB - Megakaryocyte (MK) colony growth of bone marrow mononuclear non-adherent cells was evaluated in 28 patients with essential thrombocythaemia (ET) and in 26 normal controls. The number of MK-colony forming units (CFU-MK per 3 x 10(5) plated cells) was similar in ET (68 +/- 33) and in controls (63 +/- 37), independently of bone marrow accessory cells. On the contrary, the size of the MK colonies was significantly (P less than 0.01) greater in ET patients. Human recombinant alpha-interferon 2a (alpha-IFN), administered to 10 patients at a dose of 3 x 10(6) IU/d s.c. for 11 +/- 3 weeks, was capable of inducing a significant (P less than 0.01) decrease in the number (from 72 +/- 16 to 31 +/- 14) and size of bone marrow CFU-MK, together with a significant reduction of the platelet count (from 1031 +/- 325 to 378 +/- 75 x 10(9)/l). When added in vitro at time 0 to the culture dishes, alpha-IFN inhibited the CFU-MK growth of both normal and ET bone marrow samples, even at very low concentrations (1 and 10 IU/ml). This study demonstrates that alpha-IFN, both in vivo and in vitro, exerts an inhibitory effect on the growth of MK progenitors, which appears to correlate with the clinically documented antiproliferative effect of this cytokine. PMID- 2923805 TI - The frequency of long-term remission in patients with acute myelogenous leukaemia treated with conventional maintenance chemotherapy: a study of 760 patients with a minimal follow-up time of 6 years. AB - Remission duration associated with the administration of conventional maintenance chemotherapy to patients with acute myelogenous leukaemia was evaluated. The records of 760 patients who entered remission between 1974 and 1979 were reviewed. The median duration of remission was 1.1 years with 16% of patients remaining in remission at 8 years. The relapse curve was biphasic with a high rate of relapse during the first 2 1/2 years of remission followed by a much lower relapse rate thereafter. Leukaemic relapses were noted through 8 years of remission. A plateau phase indicating freedom from the risk of leukaemic recurrence is not clearly apparent yet but may exist after the eighth year of remission. PMID- 2923806 TI - Nucleoside transport in acute leukaemia and lymphoma: close relation to proliferative rate. AB - The proliferation of mammalian cells requires nucleosides which are provided either by de novo synthesis or by influx of nucleosides via membrane transporters with subsequent metabolic trapping. In this study the density of nucleoside transporters in freshly-isolated blast cells from patients with leukaemias and lymphomas was quantitated by equilibrium binding of 3H-nitrobenzylmercaptopurine riboside (NBMPR). In acute myeloid leukaemia (AML) the density of NBMPR binding sites on blast cells ranged from 3800 to 24,200 sites/cell and this value correlated with the 3H-thymidine labelling index (1-20%) which was used to measure proliferative rate (r = 0.80, P less than 0.001). Cells from patients with Burkitt's lymphoma, other B-cell lymphomas, T-lymphoblastic lymphoma and large cell lymphoma gave a 20-fold range of NBMPR site densities (from 3700 to 75,300 sites/cell) and site numbers correlated closely with the labelling index (r = 0.87, P less than 0.001). Non-proliferating cells from patients with chronic lymphocytic leukaemia expressed the lowest density of NBMPR binding sites (850 2900 sites/cell). Comparison of bone marrow and peripheral blood blasts confirmed the positive correlation between NBMPR binding sites and labelling index for four individual patients. In contrast, the density of NBMPR binding sites on lymphoblasts from non-T acute lymphoblastic leukaemia (ALL) was low (2300-7400 sites/cell) and showed little dependence on proliferation over a wide range of labelling indices (1-20%). No correlation was observed between NBMPR site density and cell size measured by the intracellular water space. Thus an increased proliferative rate of AML or lymphoma is associated with higher numbers of nucleoside transporters in the cell membrane. PMID- 2923807 TI - In vitro studies of ways to overcome resistance to VAMP--high dose melphalan in the treatment of multiple myeloma. AB - Myeloma colonies (MY-CFUc) from 7/24 patients undergoing treatment with VAMP (vincristine, adriamycin and methyl prednisolone) and high dose melphalan (HDM) were melphalan-resistant. It was not possible to conclude that VAMP induced melphalan resistance in MY-CFUc, but that resistance is endogenous in some myeloma cell populations. In 12/13 of the same patients of whom four had MY-CFUc which were melphalan resistant, the sensitivity of MY-CFUc and GM-CFUc to busulphan was similar. Thus resistance of MY-CFUc to melphalan did not confer resistance to busulphan. MY-CFUc from 1/7 of a second group of patients were adriamycin-resistant. This resistance was removed when the cells were treated with a combination of verapamil (3 micrograms/ml) and adriamycin. Verapamil also enhanced the toxicity of adriamycin to MY-CFUc from two patients where there was no evidence for adriamycin resistance. In these three patients the sensitivity of both MY-CFUc and GM-CFUc was similar after treatment with verapamil. Verapamil did not affect the uptake or efflux of 3H-daunorubicin in sensitive and resistant RPMI-8226 cells (myeloma) and peripheral blood mononuclear cells from a normal donor; neither did it affect the binding of 3H-daunorubicin to nucleic acid. It is concluded that verapamil may be a useful adjuvant to VAMP chemotherapy and that busulphan may provide an alternative to melphalan in patients whose myeloma cells are melphalan resistant. PMID- 2923808 TI - Pre-B and 'common' lymphoblastic leukaemia of childhood compared. AB - Consecutive children suffering from pre-B lymphoblastic leukaemia (pre-B ALL) were compared with those who had 'common' ALL (C-ALL) to assess any clinical and pathological differences between the two groups. Over 101 months 27 pre-B children were seen-an incidence in the population served of around 0.8/100,000 per year. There was some time-clustering and 12 of the 27 presented in one year (1987). The 51 patients with C-ALL who presented for comparison were distributed more evenly over the study period. Pre-B children had more basophilic blast cells with less periodic acid-Schiff positivity. They had higher presenting white cell counts and serum concentrations of lactic dehydrogenase; two variables which were correlated with each other. There was a trend towards pre-B children being younger and fewer had hyperdiploid blasts, but these differences were not statistically significant. No difference from 'common' ALL in response to therapy was apparent for the pre-B patients at a median follow up time of 17 months--too short a period for any conclusion to be drawn. Other than immunophenotype, pre-B ALL has no pathognomonic features, but there are differences from C-ALL in the distribution of some disease characteristics known to be associated with a worse prognosis. PMID- 2923809 TI - The beneficial effects of alpha IFN in CGL are probably not mediated by NK cells. AB - Natural killer (NK) cells in CGL were measured phenotypically (by Leu7 and CD16 Mab staining) and functionally (by a standard chromium-release cytotoxicity assay) in eight patients before and during alpha-IFN therapy. Before alpha IFN therapy, phenotypic NK cells were normal in relative and absolute numbers but were consistently defective functionally; this defect was partially corrected by in vitro exposure to alpha IFN. During alpha IFN therapy, there was no change in NK function in five patients and enhanced (two patients) or reduced (one patient) activity was observed in the other three. Cold-target inhibition experiments showed no evidence of NK binding to normal or CGL myeloid progenitors. It is concluded that alpha IFN-enhanced NK function, a known anti-tumour mechanism in animal models, is probably not the basis of the responsiveness of CGL to alpha IFN therapy. PMID- 2923810 TI - Hairy cell leukaemia: observations on natural killer activity in different clinical stages of the disease. AB - Follow-up studies of natural killer (NK) cells, NK activity and antibody dependent cellular cytotoxicity (ADCC) in the course of hairy cell leukaemia (HCL) were carried out in a series of patients affected by the disease. NK activity against K562 targets was found to be high in all the patients with non symptomatic stable disease. On the other hand, absent or extremely low NK activity was found only in patients with symptomatic progressive disease. NK activity determined in the transitional stages showed values between these two extremes. Antibody dependent cellular cytotoxicity (ADCC) was less closely correlated with the clinical stage than NK activity. Our findings suggest that investigation of in vitro NK cell cytotoxicity might serve as a useful adjunct in determining clinical stage in HCL. PMID- 2923811 TI - Late onset bone marrow failure associated with proximal fusion of radius and ulna: a new syndrome. AB - Members of two unrelated families, one from England and the other from Portugal, presented with aplastic anaemia. Both families had clinical and laboratory features in common. The proposita presented with progressive bone marrow failure in adult life involving all three haemopoietic cell lines. In both families individuals with bone marrow failure also had proximal fusion of the radius and ulna bilaterally which segregates as an autosomal dominant trait. No cytogenetic defect was identified in myeloid or lymphoid cells, sampled from the marrow and peripheral blood. Proximal fusion of the radius and ulna is uncommon and its co existance with late onset bone marrow failure may indicate an association. Growth failure, non-skeletal congenital malformations and cytogenetic abnormalities were absent suggesting that this syndrome is distinct from Fanconi's anaemia. The onset in adult life of generalized bone marrow failure involving all three haemopoietic cell lines associated with proximal fusion of the radius and ulna also makes this syndrome distinct from the thrombocytopenia with absent radii (TAR) syndrome. PMID- 2923812 TI - Amegakaryocytic thrombocytopenia with duplication of part of the long arm of chromosome 3. PMID- 2923813 TI - Mitoxantrone induced congestive heart failure in patients previously treated with anthracyclines. PMID- 2923814 TI - Chromosome rearrangement, t(6;14) (p21.1;q32.3), in multiple myeloma. PMID- 2923815 TI - Prolonged survival in chronic granulocytic leukaemia associated with loss of the Philadelphia chromosome. PMID- 2923816 TI - Sickle cell anaemia in a septuagenarian. PMID- 2923817 TI - Tumour necrosis factor in B chronic lymphocytic leukaemia. PMID- 2923818 TI - Ristocetin and platelet aggregation. PMID- 2923819 TI - Ki67 expression in childhood acute lymphoblastic leukaemia and relation with L2 morphology. PMID- 2923820 TI - Sleep pattern disturbances related to neurological dysfunction. PMID- 2923821 TI - Neurobehavioural effects of short duration exposures to acetone and methyl ethyl ketone. AB - A total of 137 volunteers were recruited and tested for neurobehavioural performance before, during, and after a short duration (4 h) exposure to acetone at 250 ppm, methyl ethyl ketone (MEK) at 200 ppm, acetone at 125 ppm with MEK at 100 ppm, or a placebo. Ethanol (95%-0.84 ml/kg) was used as a positive control. Performance testing was computer controlled and took place in an environmental chamber with four test stations. The total test regimen before, during, and after exposure covered 10 hours and 32 measures were collected. The measurements were extracted from two biochemical (venous blood and alveolar breath) tests, four psychomotor (choice reaction time, visual vigilance, dual task (auditory tone discrimination and tracking), memory scanning) tests, one sensorimotor (postural sway) test, and one psychological (profile of mood states (POMS] test. The exposure to 250 ppm acetone produced small but statistically significant changes in performance from controls in two measures of the auditory tone discrimination task and on the anger hostility scale (men only) of the POMS test. Neither MEK nor the combined acetone/MEK exposures produced statistically significant interpretable results. The combination exposure provides some indication that there was no potentiation of the acetone effects with the coexposure to MEK or vice versa. More pronounced performance decrements occurred with ethanol at 0.07 0.08% BAC. Significant (less than 0.05) differences were evident on both the auditory tone and tracking tests in the dual task and there was partial significance on the visual vigilance test (0.05-0.06) and some postural sway measures (less than 0.09). These findings agree with an earlier Japanese study in showing some mild decrements on behavioural performance tests with exposures to acetone at 250 ppm. PMID- 2923822 TI - Urinary t,t-muconic acid as an indicator of exposure to benzene. AB - A method for rapidly determining t,t-muconic acid (MA) by high performance liquid chromatography was developed and successfully applied to urine samples from 152 workers exposed to benzene (64 men, 88 women) and 213 non-exposed controls (113 men, 100 women). The MA concentrations in urine correlated linearly with time weighted average benzene concentrations in the breath zone air of workers. A cross sectional balance study showed that about 2% of benzene inhaled is excreted into the urine as MA. The MA concentrations in the urine of the non-exposed was below the detection limit (less than 0.1 mg/l) in most cases, and the 95% lower confidence limit of MA for those exposed to benzene at 5 ppm (5.0 mg/l as a non corrected value) was higher than the 97.5%-tile values for the non-exposed (1.4 mg/l). In practice, it was possible to separate those exposed to 6-7 ppm benzene from the non-exposed by means of urine analysis for MA. The urinary MA concentration was suppressed by coexposure to toluene. PMID- 2923823 TI - Changes in lung function after working with the shotcrete lining method under compressed air conditions. AB - Shotcrete techniques under compressed air are increasingly applied in the construction of tunnels. Up to now little is known about the influence of shotcrete dusts on the function of the lung. The lung function of 30 miners working with shotcrete under compressed air (before and after one shift) was measured. They carried personal air samplers to assess the total dust exposure. Long term effects were studied on a second group of 29 individuals exposed to shotcrete dusts and compressed air for two years. A significant increase of airway resistance and a significant decrease of some flow-volume parameters were found after one workshift. These changes partially correlate close to the dust exposure. After two years exposure a significant decrease of mean expiratory flow (MEF)50 and MEF25 was found. These results point to damage in the small airways and emphasise the major role of the lung function test--including the flow-volume manoeuvre for the medical examination of the workers. Additionally, they should carry filter masks. PMID- 2923825 TI - Outcome of retrospective cohort studies and study size: a publication bias? PMID- 2923824 TI - Conjugated serum bile acid concentrations in workers exposed to low doses of toluene and xylene. PMID- 2923826 TI - Phenoxy herbicides and non-Hodgkin's lymphoma in New Zealand: frequency and duration of herbicide use. PMID- 2923827 TI - Occupational bladder cancer and the hospital clinician. PMID- 2923828 TI - Cancer mortality in a cohort of United Kingdom steel foundry workers: 1946-85. AB - The mortality experienced by a cohort of 10,491 United Kingdom steel foundry workers during the period 1946-85 has been investigated. These workers were all male operatives first employed in any one of the 10 participating foundries in 1946-65; all had worked in the industry for a minimum period of one year. Compared with the general population of England and Wales, statistically significant excesses relating to cancer mortality were found for cancer of the stomach (E = 77.4, O = 106, SMR = 137) and cancer of the lung (E = 229.2, O = 441, SMR = 147). A statistically significant deficit was found for cancer of the brain (E = 19.4, O = 10, SMR = 51). Involvement of occupational exposures was assessed by the method of regression models and life tables (RMLT). This method was used to compare the duration of employment in the industry, in "dust exposed" jobs, in "fume exposed" jobs, in foundry area jobs, in fettling shop jobs, and in foundry area or fettling shop jobs, of those dying from cancers of the stomach and lung with those of all matching survivors. The RMLT analyses provided evidence of an occupational involvement in the risk of death from lung cancer from work in the foundry area or fettling shop, and weaker evidence of an occupational involvement in the risk of death from stomach cancer from work in the foundry area. PMID- 2923829 TI - Cancer incidence and mortality among Swedish smelter workers. AB - Cancer incidence was analysed in a retrospective cohort of 3710 male Swedish smelter workers between 1958 and 1982 using a record linkage with the Swedish Cancer Register. During this period 467 cancers were registered in the cohort. An excess incidence of total cancer of about 30% was shown relative to general and local populations mainly due to 120 respiratory cancers. Excess SMRs for all cancer and respiratory cancer were highly significant. Trends in the incidence of cancer were studied using moving five year calendar periods. A decreasing rate of lung cancer was found during 1976-80 for both mortality and incidence. Incidence figures for two more years show a continued decreasing trend. This is validated by an analysis of different employment cohorts, taking latency into account, showing that the later the date of first employment the lower the incidence of cancer, especially for lung cancer. PMID- 2923830 TI - Incidence of cancer and mortality among employees in the asbestos cement industry in Denmark. AB - In a cohort study of the incidence of cancer and mortality among 7996 men and 584 women employed in the Danish asbestos cement industry between 1928 and 1984 over 99% were traced. Chrysotile asbestos was the only fibre type used until 1946, when amosite and (in 1952) crocidolite were also introduced. Chrysotile constituted 89%, amosite 10%, and crocidolite 1% of the asbestos used. During the first 25 years of manufacture the exposure levels were high, especially in areas where the asbestos was handled dry. Measurements from 1948 indicate that the fibre levels may have ranged from 100 to 1600 times over the present Danish threshold limit value of 0.5 fibre/ml. In 1973 more than 41% of personal samples were higher than 2 f/ml. About 76% of the workforce left the factory within five years of starting employment. A total of 1346 deaths and 612 cases of cancer were observed in the cohort between 1943 and 1984. Among employed men the overall mortality (O/E 1.18; 95% CI 1.12-1.25), cancer mortality (O/E 1.32; 95% CI 1.19 1.46), and overall incidence of cancer (O/E 1.22; 95% CI 1.12-1.32) were significantly increased compared with all Danish men. This was not so among employed women. For men, significant excess risks were found for cancer of the lung (O/E 1.80; 95% CI 1.54-2.10), pleura (O/E 5.46; 95% CI 2.62-10.05), mediastinum (O/E 5.00; 95% CI 1.01-14.61), stomach (O/E 1.43; 95% CI 1.03-1.93), and other male genital organs (O/E 3.03; 95% CI 1.11-6.60). The mortality was significantly increased for men for non-malignant pulmonary diseases (O/E 1.63; 95% CI 1.33-1.98). Among the group of asbestos cement workers with first employment 1928-40 an excess risk of laryngeal cancer was found (O/E 5.50;95% CI 1.77-12.82). A total of 12 cases of pleural and one of peritoneal mesotheliomas was observed when the original notification forms were reviewed for all patients with cancer in the cohort. PMID- 2923831 TI - Progression of asbestos effects: a prospective longitudinal study of chest radiographs and lung function. AB - From an original prospective cohort of 244 current and ex-workers in two asbestos cement plants, longitudinal radiographic data covering ten years were available for 165 and lung function data covering about six years for 150. Estimates of average and cumulative dust exposure were available for each participant, all men. Radiographic progression (onset or worsening) was assessed by comparing earliest and latest films side by side. Annual changes in lung function were computed by fitting regression lines to all the data points. Small opacities (ILO category 1/0 or higher) were found in 16% of initial films, and progression of small opacities occurred in 13% of film pairs. Average and cumulative dust exposure were each significant determinants of the initial presence of small opacities, and were determinants of the progression of both parenchymal and pleural abnormalities. There was greater likelihood of progression if an abnormality was initially present, and a greater likelihood of progression in the plant that had systematic use of some crocidolite. Initial levels of lung function were related to smoking, exposure to dust, and initial radiographic status. Mean annual declines in lung function were modest (FVC-0.017 l/y, FEV1 0.020 l/y) and were related to smoking but not exposure to dust, initial radiographic status, or radiographic progression. Both plants used mainly chrysotile asbestos and exposure levels declined severalfold after 1960. Our findings suggest a waning effect of the larger remote dust exposures on recent annual change in lung function. This accords with human and experimental pathology data showing the relatively low resistance of chrysotile fibres to chemical alteration and clearance. PMID- 2923832 TI - Division of uterine adhesions (Asherman's syndrome) with the Nd-YAG laser. AB - Two women with Asherman's syndrome after postpartum curettage are presented. The diagnosis was confirmed by hysteroscopy. The adhesions were vaporized under hysteroscopic control, using a Nd-YAG laser (neodymium-yttrium-aluminium-garnet laser). The method was precise, caused minimal thermal injury and resulted in immediate return of regular menstrual cycles. The use of the Nd-YAG laser for Asherman's syndrome warrants further study. PMID- 2923833 TI - Clinical characteristics of subfertile men with antisperm antibodies. AB - This study investigated the clinical features which could serve as markers to identify subfertile men with antisperm antibodies including age, duration of infertility, history of abdominal or perineal surgery and previous genital trauma. Of the 162 men studied, 43 had a positive test for antisperm antibodies. A significantly greater number of these patients had a history of genital trauma and appendicectomy. Whereas the aetiological role of genital trauma in spermatozoal autoimmunity is readily explicable, that of appendicectomy is not. It can only be postulated that inflammation of the appendix may sometimes affect the vas deferens or that there is some inadvertent injury to the vas deferens during appendicectomy. PMID- 2923834 TI - Primary malignant Schwannoma of the uterine cervix. Case report. PMID- 2923835 TI - Pelvic inflammatory disease caused by Salmonella panama and its treatment with ciprofloxacin. Case report. PMID- 2923836 TI - Cervical stenosis after cone biopsy during post-pregnancy amenorrhoea. PMID- 2923837 TI - Commentary. Broken bones--a gynecological problem. PMID- 2923838 TI - A study comparing transcervical with trans-abdominal chorionic villi sampling (CVS) PMID- 2923839 TI - The pathogenesis of genitourinary prolapse and stress incontinence of urine. A histological and histochemical study. AB - Histological and histochemical analysis of biopsy samples of pubococcygeus muscle obtained from asymptomatic women and from women with stress incontinence of urine, with or without genitourinary prolapse, have been compared. In the asymptomatic women both age and parity appeared to be related to the morphological features of the samples and in particular those obtained from the posterior part of the pubococcygeus. In the symptomatic women there was a significant increase in the number of muscle fibres showing pathological damage which were obtained from the posterior part of the pelvic floor. The range of diameters of both Type I and Type II fibres obtained from this region was significantly different between symptomatic and asymptomatic women. These findings may be attributable to partial denervation of the pelvic floor in patients with urinary stress incontinence with or without genital tract prolapse. PMID- 2923840 TI - The role of partial denervation of the pelvic floor in the aetiology of genitourinary prolapse and stress incontinence of urine. A neurophysiological study. AB - Single-fibre electromyography of the pubococcygeus muscle of the pelvic floor was performed in 69 asymptomatic women and 105 women with stress incontinence of urine or genitourinary prolapse or both. The results suggest that partial denervation of the pelvic floor with subsequent reinnervation is a normal accompaniment of ageing and is increased by childbirth. Women with stress incontinence of urine or genitourinary prolapse or both have a significant increase in denervation of the pelvic floor compared with asymptomatic women. PMID- 2923841 TI - The role of pudendal nerve damage in the aetiology of genuine stress incontinence in women. AB - Conduction was studied in the terminal branches of the pudendal nerve in 42 women with normal urinary control and 87 women with stress incontinence of urine, genitourinary prolapse, or both. Women with stress incontinence of urine had delayed conduction to both the striated urethral muscle and the pelvic floor muscle, indicative of denervation injury. Women with normal urinary control and genitourinary prolapse had similar conduction times to the urethral sphincter striated muscle as normal women but clear evidence of denervation damage to the pelvic floor. PMID- 2923842 TI - Serum from pregnant women carrying a fetus with neural tube defect is teratogenic for rat embryos in culture. AB - Sera from 13 pregnant women carrying a fetus with a neural tube defect, and from 13 control women with normal pregnancies at the same stage of gestation were used in the culture of postimplantation rat embryos. Serum from women with normal pregnancies had no adverse effect on rat embryo growth and development. Serum from 10 of the women with affected fetuses had a deleterious effect on the rat embryos as abnormalities of neural tube closure were observed in 28% of the conceptuses compared to only 1.3% of the embryos cultured in control serum. PMID- 2923843 TI - Measurement of cardiac output in pregnancy by thermodilution and impedance techniques. AB - To assess the value of impedance cardiography in pregnancy, simultaneous measurements of cardiac output were made with impedance and thermodilution techniques in 10 patients who required pulmonary artery catheterization. The methods correlated poorly (r = 0.17). The discrepancy between methods was particularly pronounced in hypertensive patients. Impedance cardiography does not measure cardiac output accurately in hypertensive pregnant women. PMID- 2923844 TI - Aldosterone is secreted intermittently during pregnancy. AB - Saliva aldosterone concentration was measured in samples collected at hourly intervals from healthy pregnant women (approximately 26 and 36 weeks gestation) who were going about their normal daily activities, and from some women hospitalized for disorders of pregnancy. In the healthy women diurnal saliva aldosterone fluctuated considerably, the highest values being 2-22 times the lowest on a given day. Because of the known correlation between saliva and plasma aldosterone concentrations we believe that the fluctuating salivary level is indicative of fluctuating plasma levels and that this is due to the intermittent secretion of aldosterone. The rate of decline of saliva aldosterone from peak levels indicated a half life (t 1/2) of 72 (SD 31) min which was not significantly different from that in non-pregnant subjects. The temporal pattern of saliva aldosterone suggests an enhanced response of the zona glomerulosa to the factors that cause aldosterone secretion to fluctuate in non-pregnant subjects, rather than the development of a more potent stimulus to the zona glomerulosa during pregnancy. In addition to hour-to-hour variation there is also substantial day-to-day variation, so that estimation of aldosterone in a single sample of saliva or plasma is of little value during pregnancy. The mean diurnal aldosterone concentration can be estimated from five saliva samples so this measurement presents a convenient technique for the assessment of aldosterone status in pregnancy. In contrast to healthy pregnancy, a patient with pre eclampsia at 39 weeks gestation showed no elevation of saliva aldosterone above non-pregnant levels at any time during the day. PMID- 2923845 TI - Cigarette smoking in pregnancy results in marked decrease in maternal hCG and oestradiol levels. AB - We have examined serum levels of oestradiol (E2), sex-hormone binding globulin (SHBG) and human chorionic gonadotrophin (hCG) during early pregnancy in relation to smoking status at the time of sampling in a series of 147 women. Smoking was associated with significantly depressed serum levels of E2, SHBG and hCG: in smokers, E2 levels were on average 17.6% lower (P = 0.037), SHBG levels were 12.4% lower (P = 0.15), and hCG levels were 21.5% lower (P = 0.044). There appeared to be a steady decline in these values with increasing cigarette consumption. These lower hormone levels in smokers may explain certain adverse effects of smoking in pregnancy. PMID- 2923846 TI - Problems of peritoneal access in intraperitoneal treatment and monitoring of ovarian cancer. AB - A total of 154 peritoneal lavages was attempted through either a permanent (17) or a temporary percutaneous cannula (137) in 59 ovarian cancer patients undergoing intraperitoneal treatment or monitoring. Seven of the eight permanent catheters were removed because of complications; intraperitoneal adhesions were a major problem in this group. Overall, 137 temporary catheters were inserted (14G Venflon i.v. cannula in 119, Verres needle in 15, and a Trocath peritoneal dialysis catheter in 3 instances) but it was not possible to perform a peritoneal lavage in 42 (30%). Access to the peritoneal cavity was unsatisfactory on 29 (34%) occasions when a Venflon cannula was used, either because there was inadequate flow of lavage fluid into the peritoneal cavity or this was limited by pain. Perforation of the bowel occurred in 12 (9%) cases but there was no significant morbidity. Problems with achieving reliable peritoneal access using either permanent or temporary catheters may limit the potential advantages of the intraperitoneal route for treatment and monitoring. PMID- 2923847 TI - A retrospective cephalometric study of Class I patients. AB - In view of the growing consensus that traditional cephalometric analyses yield data of dubious scientific validity, this study was undertaken using an alternative technique, termed finite element analysis (FEA). The study was based on 14 triangular finite elements spanning seven datum (nodal) points delineating cephalometric form. These points were delineated on lateral cephalographs taken immediately before and following the completion of orthodontic treatment for two samples of boys aged 12-16 years. Although both samples exhibited Class I molar occlusions with anterior over-crowding, one sample required bilateral maxillary and mandibular first premolar extraction prior to orthodontic treatment, while the other sample did not. FEA revealed greater cephalometric size and shape changes in the 'non-extraction' than 'extraction' samples. Such sample contrasts, however, varied depending upon the finite element included in the analysis. Further studies are therefore required to delineate the specific finite element configurations to provide precise descriptions of cephalometric change. PMID- 2923848 TI - The reliability of mandibular radiographic superimposition. AB - Using tracings from thirty pairs of serial cephalometric radiographs, the reliability of three outlines, commonly used for mandibular superimposition, was investigated. There were sizeable errors associated with all three groups, but tracings involving Bjork's mandibular structures were found to be the least reliable. Despite the greater validity of the Bjork structures for assessment of growth changes, in certain cases the use of the mandibular outline may be of greater value for the superimposition of tracings, especially when the time interval between the radiographs is short, or the patient has passed maturity and the growth rate has declined to a negligible level. PMID- 2923849 TI - A cephalometric investigation of overjet changes in fifty severe Class II division I malocclusions. AB - A retrospective cephalometric study of 50 consecutively completed Class II Division I malocclusion cases was carried out in order to analyse the resultant data for craniofacial features which might act as predictors for successful overjet reduction. All the patients had clinically measured overjets of between 10 mm and 15 mm at the start of treatment. The sample was subsequently divided into two groups depending on whether or not the overjet had been reduced to 4 mm or less at the end of treatment. No firm predictors were found, but the most favourable results were achieved with the Begg appliance. PMID- 2923850 TI - Richard Marx--Begg appliance treatment. Interview by Robert Kirschen. PMID- 2923851 TI - Morphology of the maxillary lateral incisor in cases of unilateral impaction of the maxillary canine. AB - Two groups of subjects who demonstrated unilateral maxillary canine impaction were examined, a Caucasian group and an Oriental group. It was found that there are significant differences between the groups for sex of patients seeking treatment, site of impaction (buccal/palatal), and arch form. The Oriental group was significantly more crowded in the canine area than the Caucasian group. In almost all cases the dimensions of the lateral incisor on the side of impaction were smaller than the non-impacted side, although five subjects from the Caucasian female sub-group did not conform to this pattern, and for the Oriental male sub-group the mesiodistal crown width was larger on the impacted side. PMID- 2923852 TI - The importance of the form of nitrogen on microbial protein synthesis in the rumen of cattle receiving grass silage and continuous intrarumen infusions of sucrose. AB - 1. In a 4 x 4 Latin square design experiment, four cattle were given grass silage in two meals per d to satisfy maintenance energy requirements. In addition, sucrose (170 g/kg silage dry matter (DM] was infused intraruminally at a constant rate with no nitrogen supplementation; with the infusion intraruminally of either casein (23 g/kg silage DM) or urea (8 g/kg silage DM); or with soya-bean meal (64 g/kg silage DM) fed in two equal portions. 2. Samples of duodenal digesta representative of a 24 h period were obtained using chromium-EDTA and ytterbium acetate for flow estimation and 35S as a marker of microbial N entering the small intestine. Samples of rumen fluid were also taken for estimation of rumen pH and concentrations of ammonia-N and volatile fatty acids. Estimates of apparent organic matter (OM) and N digestibility and of the rates of silage DM and N disappearance from porous synthetic-fibre bags incubated in the rumen were also made. 3. The N supplements had no significant effects on rumen pH, concentrations of volatile fatty acids, their molar proportions or the disappearance of DM or N from porous synthetic-fibre bags. N supplementation increased rumen ammonia-N concentrations (urea, P less than 0.05; casein, soya-bean meal, not significant). 4. N supplementation had no significant effects on the digestion of OM, acid detergent fibre or soluble carbohydrate. 5. Infusion of casein increased the quantities of total non-ammonia-N (not significant) and microbial N (P less than 0.05) entering the small intestine daily and the efficiency of rumen microbial N synthesis (not significant).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2923853 TI - Dental and metabolic effects of lactitol in the diet of laboratory rats. AB - 1. Because so little is known about the properties of lactitol as a possible alternative bulk sweetener to sucrose, it was tested in two large-scale experiments in laboratory rats. Matched groups of caries-active Osborne-Mendel rats were fed on uniform diets containing lactitol and compared with a sucrose control in both experiments, plus a xylitol control in the first experiment. 2. In the early stages of the experiments weight gains and food utilization were better on the sucrose than on the lactitol regimens. Body-fat storage was higher on the sucrose than on the polyol regimens. 3. At the end of 8 weeks the mandibular molars were examined for dental plaque accumulation and dental caries. The dental caries scores when 160 g sucrose/kg in the diet was replaced by lactitol were lower by a highly significant margin, bringing them down to the same low level as those on a 160 g xylitol/kg regimen. 4. Testing lactitol in a manufactured food product, shortbread biscuits, in comparison with ordinary sucrose biscuits, showed differences in plaque scores (significant) and caries levels (highly significant), with 60% fewer lesions on the lactitol regimen. 5. The results confirm the low cariogenic potential of lactitol, but show metabolic differences compared with sucrose. PMID- 2923854 TI - The role of the Journal in the 1900s. PMID- 2923855 TI - Physiological changes associated with the production of defective egg-shells by hens receiving sodium chloride in the drinking water. AB - 1. Supplementing the drinking water of laying hens with 600 or 2000 mg sodium chloride/l induced large increases in egg-shell defects without corresponding changes in egg production, egg weight or food and water intakes. A supplement of 2000 mg NaCl/l resulted in a high incidence of shell-less eggs. 2. The increased incidence of egg-shell damage in hens receiving the NaCl was associated with a decrease in egg-shell quality measured objectively. These responses persisted even after the NaCl was removed from the drinking water. 3. The NaCl treatment had little effect on blood acid-base balance and electrolytes, but significant reductions were observed in the carbon dioxide tension, and bicarbonate and calcium concentrations in the fluid surrounding the egg in the shell gland. 4. The poor shell quality appeared to be associated with a reduced supply of bicarbonate, rather than with an effect on Ca, in the lumen of the shell gland, although a reduced residence time of eggs in the shell gland may also have contributed to the problem. PMID- 2923856 TI - Kinetic aspects of calcium metabolism in lactating sheep offered herbages with different Ca concentrations and the effect of protein supplementation. AB - 1. Two experiments are described in which kinetic aspects of calcium metabolism were studied in housed lactating sheep consuming different fresh herbage species. The importance of protein supply was also investigated. 2. In Expt. 1, two groups (n 4) were offered, ad lib., a freshly cut ryegrass (Lolium perenne L.)-white clover (Trifolium repens L.) pasture containing 5.48 g Ca/kg dry matter (DM). One group was supplemented daily with 100 g protected casein. A third group (n 4) was offered, ad lib., freshly cut oats-Tama ryegass (Lolium multiflorum L.) herbage which had a lower Ca content of 3.07 g Ca/kg DM. Stable Ca and nitrogen balances were carried out during the first 7 weeks of lactation. At this stage 180 microCi 45Ca were administered for Ca kinetic studies. 3. In Expt 2, eight sheep were offered, ad lib., a fresh ryegrass-white clover pasture, and paired on the basis of their udder size. One member of each pair was supplemented daily with 100 g casein via the abomasum and the amount of milk removed was equalized between pairs. Ca and N balance (12 d) and) and Ca kinetic studies (280 microCi 45Ca) were carried out during weeks 2 and 5 of lactation. 4. Rate of absorption of Ca increased, while rate of Ca secretion in milk and resorption from bone decreased as lactation progressed. Ca balances changed from negative to positive as lactation progressed in sheep offered ryegrass-white clover, but, while improving, were always negative in sheep offered oats-Tama ryegrass. Protein supplementation increased (18%) milk production of the ewes in Expt 1 and their retention of N in Expt 2. 5. The proportion of utilized Ca derived from the diet, as opposed to the skeleton, tended to increase as a result of protein supplementation. 6. Availability of Ca from ryegrass-white clover ranged from 0.19 to 0.32, even though only 50% of the net Ca requirement was derived from the diet. Availability of Ca from the oats-Tama ryegrass diet was similar, though in this case less than 20% of the net Ca requirement was derived from the diet. It was concluded that availability of Ca from forage diets may be lower than previously anticipated. 7. Faecal endogenous loss ranged from 16 to 40 mg Ca/kg body-weight per d, and was similar on both diets.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2923857 TI - Faecal endogenous loss of calcium in young sheep. AB - 1. Two groups of eight 6-7-month-old wether lambs were offered either a frozen ryegrass (Lolium perenne L.)-white clover (Trifolium repens L.) pasture or a ryegrass-white clover hay, containing 12.1 and 6.4 g calcium/kg dry matter (DM) respectively. Within groups the amounts offered to individual sheep ranged from 0.5 to 2.0 times the estimated maintenance energy requirements. 2. A single intravenous injection of 150 microCi 45Ca as CaCl2.2H2O, and stable balances were used to determine absorption, faecal endogenous loss and balance of Ca. 3. Faecal endogenous loss of Ca increased by 1.2 mg/kg body-weight (W) per d with each g/kg W per d increase in DM intake regardless of the diet. At any DM intake the mean faecal endogenous loss was 5.5 mg/kg W per d higher in the sheep offered the frozen herbage diet when compared with those on the hay diet. At any Ca intake the mean faecal endogenous loss was 6.9 mg/kg W higher in sheep offered the hay diet compared with those on the frozen herbage. 4. At feeding levels of about 1.5 2 times the estimated maintenance energy requirement the observed faecal endogenous loss of Ca ranged from 35 to 50 mg/kg W per d, which is two- to threefold greater than the present estimate of the Agricultural Research Council (1980) of 16 mg/kg W per d.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2923858 TI - Minerals and trace elements in total diets in The Netherlands. AB - 1. During a period of 2.5 years, every 3 months 221 different food items forming a 'market basket' were purchased, prepared and divided into twenty-three food commodity groups. The 'market basket' was based on a study of the dietary intake of 18-year-old male, Dutch adolescents. In the (homogenized) food groups various minerals and trace elements were determined. 2. The mean daily amounts of cadmium (21 micrograms), mercury (0.7 micrograms), lead (32 micrograms), tin (0.65 mg), arsenic (38 micrograms) and bromine (8 mg) in the diet of adolescents, as calculated from the concentrations analysed in the food groups, were all (well) below the Food and Agriculture Organization/World Health Organization acceptable daily intake (ADI) value (Codex Alimentarius Commission, 1984). 3. The mean daily amounts of zinc (14 mg) and selenium (72 micrograms) seemed to be adequate compared with the Dutch recommendations, (Voedingsraad (Dutch Nutrition Council) 1986). The amounts of copper (mean value 1.5 mg/d) and iron (mean value 14 mg/d) in the total diet were marginal. Contents of calcium (1340 mg/d), magnesium (433 mg/d) and iodine (402 micrograms/d) were all well above the Dutch recommendations for male adolescents. Sodium intake, corresponding to 11 g sodium chloride/d, was higher than advised. 4. It is concluded that the amounts of As, Br and toxic heavy metals in Dutch total-diet samples of male adolescents are of little concern as regards health aspects. Among the essential trace elements, Fe and Cu contents seem to be marginal. Some concern regarding the salt content is indicated. PMID- 2923859 TI - Influences of biotin deficiency and dietary trans-fatty acids on tissue lipids in chickens. AB - 1. The combined effects of feeding hydrogenated fats and varying the levels of biotin and linoleate (18:2 omega 6) on polyunsaturated fatty acids were studied in the chicken. 2. Biotin deficiency signs were not exacerbated by feeding hydrogenated fats or by diets low in linoleate for 21 d. 3. Biotin deficiency resulted in proportionately higher levels of 18:2 omega 6 and gamma-linolenate (18:3 omega 6) in liver triglycerides, and lower levels of dihomo-gamma linolenate (20:3 omega 6) in liver and heart phospholipids irrespective of the 18:2 omega 6 level in the diet. 4. Biotin deficiency did not alter arachidonate (20:4 omega 6) levels in tissue lipids at 21 d. 5. Feeding high levels of trans 18:1 isomers with adequate biotin led to reduced 20:3 omega 6 and 20:4 omega 6 levels in liver and heart phospholipids with compensatory increases in omega 3 fatty acids. 6. The trans-isomers of 18:1 were incorporated into several tissues of the chick. Incorporation was dependent on the levels fed. Very small amounts were incorporated into brain compared with other tissues when dietary trans isomer levels were high, but were similar when dietary trans-isomer levels were low. The trans-18:1 isomers appear to be preferentially incorporated into phospholipids as opposed to triglycerides in heart and liver. PMID- 2923861 TI - Minimal surface tension, squeeze-out and transition temperatures of binary mixtures of dipalmitoylphosphatidylcholine and unsaturated phospholipids. AB - Fluorescence polarization (FP) measurements and surface tension (ST) experiments were performed to determine the gel-to-liquid-crystal transition or melting temperature of phospholipid mixtures. The FP-temperature diagrams showed main transition temperatures of 41 degrees C for dipalmitoylphosphatidylcholine (DPPC). The 7:3 and 9:1 binary mixtures of DPPC and phosphatidylinositol (PI), phosphatidylglycerol (PG) and phosphatidylcholine (PC) had main transition temperatures of, respectively, 32-36 degrees C and 37-39 degrees C. The minimal surface tension of DPPC monolayers increased rapidly at 40 degrees C, suggesting that this was the transition temperature for the melting of these monolayers. This value was in close accordance with the main transition temperature of DPPC, observed with the fluorescence polarization measurements. Melting temperatures of monolayers were higher for almost all mixtures than the temperatures at which the transition started, indicating preferential squeeze out of the unsaturated component and enrichment of the monolayer with DPPC. However, neither the 7:3 DPPC/PC nor the DPPC/PG mixtures could withstand high surface pressures at temperatures above 30 degrees C, whereas monolayers of DPPC/PG (9:1) became fluid at temperatures above 35 degrees C. Preferential squeeze-out of the unsaturated phospholipid was especially effective in both the 7:3 and 9:1 DPPC/PI mixtures. These monolayers started to melt at 39-40 degrees C, which is above their main transition temperatures of, respectively, 32 and 37 degrees C, and which approximate the melting temperature of DPPC. Preferential squeeze-out is essential for an artificial lung surfactant. The estimation of this phenomenon by determining the monolayer melting temperatures is therefore useful for distinguishing between mixtures which are effective surfactants at body temperature and those which are less effective. PMID- 2923860 TI - Uptake of the 35 kDa major surfactant apoprotein (SP-A) by neonatal rabbit lung tissue. AB - Secreted surfactant is made up of both phospholipid and protein components. Therefore, we investigated the possibility that surfactant apoproteins might be taken up by the alveolar type II cell in a manner similar to the uptake of surfactant phosphatidylcholines. Day 2 neonatal rabbits were infused via the trachea with a solution of carrier surfactant and 125I-labelled surfactant apoprotein (SP-A, Mr approx. 35,000). Most of the 125I-SP-A remained within the alveolus; however, a fraction of the 125I-SP-A was taken up by the lung tissue from the alveolus in a time-dependent manner. The small amount of radiolabeled material detected in blood, liver or kidney tissues of 125I-SP-A-infused animals was not trichloroacetic acid (TCA) precipitable, i.e., probably represented degradation products. In contrast, the proportion of TCA-precipitable 125I-SP-A in lung tissue or lavage samples did not change as function of time after tracheal administration. Two-dimensional gel electrophoresis of the 125I-SP-A present in the lavage samples or associated with lung tissue was used to show that a small proportion of the 125I-SP-A was partially degraded in the lung tissue and alveolus. These data are suggestive that the SP-A is taken up by lung tissue, perhaps in a manner similar to the uptake of surfactant phospholipid by the alveolar type II cell. PMID- 2923862 TI - Correlation of the dispersion state of pyrene cerebroside sulfate and its uptake and degradation by cultured cells. AB - This study aimed at increasing the efficiency and shortening the time required for administering cerebroside sulfate to cultured cells. For this purpose several modes of dispersion of a fluorescent derivative of cerebroside sulfate (sulfatide), in which the natural fatty acid has been replaced by pyrenedodecanoic acid (P12), were incubated with the cells. This fluorescent derivative of cerebroside sulfate (P12-CS) was introduced into the growth medium of the cells using the three following modes of dispersion: (1) P12-CS was dissolved in dimethylsulfoxide and added to the medium, (2) it was precomplexed with serum albumin or (3) incorporated into small, unilamellar vesicles (SUV) of phosphatidylcholine. With each of these respective modes of dispersion, the P12 CS was incubated for periods up to 48 h with cultured lymphoblasts or fibroblasts. Uptake by the cells could be determined by recording directly the cell-associated fluorescence, using a suspension of washed intact cells. The cell lipids were subsequently extracted with mixtures of chloroform/methanol and their fluorescence recorded. When related to the incubation time, uptake of P12-CS by the cells increased continuously using each of the above dispersions. The appearance of fluorescence at 475 nm ('excimer') and the ratio of this to the monomolecular fluorescence at 378 nm ('E/M') could be used as a measure for the presence of the internalized P12-CS in aggregated or fully dispersed states. These values (i.e., E/M), recorded on the suspensions of intact cells were rather high using the aqueous dispersions, intermediate values were observed using the SUV and rather low E/M values (0.5 or less) were observed using the preformed albumin-(P12-CS) complexes. Increasing the mole ratio of albumin to P12-CS (i.e., from 1:2 to 2:1 m/m), decreased the quantity of sulfatide which was taken up by the cells but also further decreased the E/M ratio, suggesting a fully dispersed state of the pyrene lipid within the cell. This indicated that, using an optimal albumin to P12-CS ratio of 1-2 (or its equivalent values in fetal calf serum) permitted an influx of single molecules of P12-CS into the cells. After 48 h, about 50% of the fluorescence of skin fibroblasts was found in metabolic degradation products of P12-CS. The parallel value for fibroblasts derived from a patient with metachromatic leukodystrophy was only about 5%. Appearance of the excimeric emission of a dispersion of P12-CS in water permitted estimation of its critical micellar concentration as being 7.5 x 10(-7) M. PMID- 2923863 TI - Contribution of cytoplasmic storage triacylglycerol to VLDL-triacylglycerol in isolated rat hepatocytes. AB - The cytoplasmic triacylglycerol (TG) storage pool of isolated hepatocytes was labelled in order to evaluate its incorporation into very low density lipoproteins (VLDL). Rats were injected with [1-14C]oleate 2 min prior to surgery and cell incubations began 90-100 min thereafter. In keeping with the equilibration of the two TG pools (in smooth endoplasmic reticulum, SER, and cytoplasm) in 120 min (Stein, Y. and Shapiro, B. (1959) Am. J. Physiol. 196, 1238 1241) the bulk of radioactive TG at time zero was in the cytoplasm and TG specific activities were similar in cytoplasm and SER. Radioactive and total VLDL TG secretions were greatly inhibited after 80 min by chloroquine which is assumed to block lysosomal hydrolysis of cytoplasmic TG. When the SER-TG pool was labelled by addition of [1-14C]oleate in vitro, chloroquine affected neither [1 14C]oleate uptake and esterification nor its incorporation into VLDL-TG from 15 20 min until 80 min. After 100 min, when [1-14C]oleate-TG was transferred back from cytoplasm to SER, chloroquine began to decrease radioactive VLDL-TG output and by 210 min caused the same inhibition as under the in vivo labelling condition. These results are consistent with an inhibition by chloroquine of the lysosomal hydrolysis of cytoplasmic TG resulting in a blockage of their back transfer to SER membranes whereas other steps of VLDL production were not affected, at least up to 100 min. This study also showed that stored TG is a quantitatively important VLDL precursor, sustaining VLDL production for several hours in the absence of exogenous fatty acids. PMID- 2923864 TI - NADP-dependent 3 beta-, 7 alpha- and 7 beta-hydroxysteroid dehydrogenase activities from a lecithinase-lipase-negative Clostridium species 25.11.c. AB - A lecithinase-lipase-negative Clostridium sp. 25.11.c., not fitting in any of the species of Clostridia described so far as judged by morphological, physiological, and biochemical data, was shown to contain NADP-dependent 3 beta-, 7 alpha- and 7 beta-hydroxysteroid dehydrogenases. The three hydroxysteroid dehydrogenases could be demonstrated in the supernatant and in the membrane fraction after solubilization with Triton X-100, suggesting enzymes which were originally membrane bound. The 3 beta-hydroxysteroid dehydrogenase was synthesized constitutively, and the specific enzyme activity was significantly reduced by growth medium supplementation with 3-keto bile acids and trisubstituted bile acids. A pH optimum of 7.5 and a molecular weight of approx. 104,000 were estimated by molecular sieve chromatography. The enzyme reduced the 3-keto group of bile acids; an oxidation of a 3 beta-hydroxyl function could not be demonstrated. The lowest Km values were found for disubstituted bile acids, trisubstituted and conjugated bile acids having higher Km values. 7 alpha Hydroxysteroid dehydrogenase, but not 7 beta-hydroxysteroid dehydrogenase, was already present in uninduced cells. The specific activities, however, were greatly enhanced when cells were grown in the presence of chenodeoxycholic acid or 3 alpha-hydroxy-7-keto-5 beta-cholanoic acid. Ursodeoxycholic acid with its 7 beta-hydroxyl group was ineffective as an inducer. Molecular weights of approx. 82,000 and 115,000 were found for the 7 alpha-hydroxysteroid dehydrogenase and the 7 beta-hydroxysteroid dehydrogenase, respectively. In contrast to the in vivo situation, the reaction could only be demonstrated in the reductive direction in vitro. Here, the pH optimum for the overall reaction was 8.5-8.7. 3 beta-, 7 alpha- and 7 beta-hydroxysteroid dehydrogenase activities were readily demonstrated for at least 48 h when preparations were stored at 4 degrees C, but were found to be heat-sensitive. PMID- 2923865 TI - Subcellular distribution of cardiac fatty acid-binding protein in bovine heart muscle and quantitation with an enzyme-linked immunosorbent assay. AB - Several types of the 14-15 kDa fatty acid-binding proteins (FABPs) are known to occur in the cytosol of mammalian cells. With antibodies raised against the cardiac-type protein from bovine heart, immunoblots indicated a more widespread distribution of the cardiac FABP in subcellular fractions, such as mitochondria and nuclei. A detailed view was obtained when the post-embedding protein A-gold labeling method was applied to cross-sections of heart cells and isolated subcellular fractions. Cardiac FABP in myocytes was associated with myofibrils and localized within mitochondria and nuclei. After subfractionation of mitochondria, the binding protein was recovered with matrix proteins only. A non competitive enzyme-linked immunosorbent assay (ELISA) of the direct type was developed specifically for bovine cardiac FABP. This assay was sensitive in the range of 0.05 to 1 ng, and concentrations of cardiac FABP per mg protein were found for cytosol, matrix and nuclei to be around 3.18, 0.18 and 0.03 micrograms, respectively. The newly found compartmentation of cardiac FABP in the heart cell must be considered when the true functions of the protein, yet to be defined, are studied. PMID- 2923866 TI - Differential methylation patterns in molecular species of phosphatidylethanolamine derivatives in rat liver membranes. AB - The appearance of individual molecular species of phospholipids in the complete sequence of the transmethylation of phosphatidylethanolamine (PE) was examined in rat liver microsomes incubated with S-adenosyl-L-[methyl-14C]methionine. Reverse phase HPLC analysis of phosphatidylcholine (PC), phosphatidyl-N,N dimethylethanolamine (dimethyl-PE), or phosphatidyl-N-monomethylethanolamine (monomethyl-PE) showed that radioactivity was present in the same six principal molecules; a first group is constituted by 16:0/22:6, 16:0/20:4 and 16:0/18:2 and a second one by the homologous molecules with 18:0 instead of 16:0 at the sn-1 position of glycerol. In PC, 16:0/22:6 (23% of total radioactivity) was preponderant, and 18:0/20:4 was the lowest. The ratios cpm in PC/nmol in PE were in the order: 16:0/22:6 greater than 16:0/18:2 greater than 16:0/20:4 followed by the corresponding 18:0 molecules. On the other hand, in intermediate phospholipids, incorporation of methyl groups was most marked in 18:0/20:4 (24 27% of total). 16:0/22:6 and 16:0/18:2 were low in comparison to their relative values in PC. The ratio (18:0/20:4)/(16:0/22:6) was 4.5-5.6-times higher in monomethyl-PE and dimethyl-PE than in PC. These differences were found consistently, regardless of incubation time of microsomes (2.5-60 min) and of S adenosyl-L-methionine (AdoMet) concentration (3 or 100 microM). In liver membranes, it would therefore seem that there is a different selectivity in methyl group transfer, depending upon whether the first two steps or the third step of the reaction are considered. Side reactions, such as deacylation/reacylation, are unlikely to account for this difference, which could rather be related to the enzyme itself. PMID- 2923867 TI - Are fatty acid-binding proteins involved in fatty acid transfer? AB - The possible function of fatty acid-binding protein (FABP) to act as a fatty acid carrier protein was investigated in model systems with regard to three aspects. (1) does FABP release fatty acids from membranes? (2) does it facilitate fatty acid transport in an aqueous environment? (3) are FABP-bound fatty acids released for use by mitochondria? FABPs could bind oleic acid from liposomes and mitochondrial membranes with a ratio of 1 mol per mol protein. Oleic acid was withdrawn from negative, neutral or cholesterol-containing monolayers by FABP with rates up to 10%/min. Only about 5% of FABP penetrated into the monolayer. Spontaneous transfer of oleic acid between mitochondria and vesicles or liposomes occurred so rapidly that an effect of FABP was not detectable. When the mitochondria were separated from the vesicles in an equilibrium dialysis cell, a stimulating effect of FABP on fatty acid transfer could be demonstrated. Injected FABP increased also transfer of oleic acid between two separate monolayers. FABP bound fatty acid was well oxidized by rat liver mitochondria. The results indicate that the FABP-fatty acid complex may function as an intermediate in the transfer of fatty acids between membranes. No functional differences were detected between heart and liver FABPs in this respect. PMID- 2923868 TI - Stimulatory effect of testosterone on renal 25-hydroxyvitamin D-3 1 alpha hydroxylase in guinea pig. AB - Castration of male guinea pigs reduced the activity of the renal mitochondrial 25 hydroxyvitamin D-3 1 alpha-hydroxylase by about 50% without affecting the apparent Km for the reaction. Testosterone substitution for 10 days after castration increased the activity to about the same level as that of sham operated animals. Ovariectomy of female guinea pigs had no effect on the 1 alpha hydroxylase activity. Administration of testosterone to ovariectomized female guinea pigs increased the activity by about 50%, again without affecting the apparent Km. The different manipulations had no significant effect on circulating levels of 1,25-dihydroxyvitamin D or vitamin D-binding protein (DBP). It is concluded that testosterone may be a regulator of the 25-hydroxyvitamin D-3 1 alpha-hydroxylase in guinea pigs. PMID- 2923869 TI - Retinoid-mediated induction of the fat-storing phenotype in a liver connective tissue cell line (GRX). AB - The GRX cell line is derived from murine liver connective tissue cells. It has myofibroblastic characteristics and can be induced to display a phenotype analogous to fat-storing (Ito) cells. Retinol-mediated induction of the fat storing phenotype was studied in vitro. Based on the incorporation of radiolabelled acetate into cell lipids, cholesterol synthesis increased and phospholipid synthesis was modified shortly after the beginning of the induction, indicating an activation of pre-existing metabolic pathways. Triacylglycerol synthesis was increased only after a delay of 4 d, indicating the de novo induction of enzymes necessary for triacylglycerol metabolism. Retinol incorporation and conversion into retinyl esters were also considerably increased by previous incubation with retinoids. Retinoid-induced changes in GRX cells provide a model for studying in vitro the interconversion of liver connective tissue cells between the myofibroblastic and fat-storing phenotypes. This interconversion is considered to be one of the major control points of normal homeostasis and of pathological modifications of liver connective tissue. PMID- 2923870 TI - 2-Deoxy-D-glucose accumulation in adipocytes: apparent transport discrimination between 2-deoxy-D-glucose and 3-O-methyl-D-glucose. AB - The uphill accumulation of free 2-deoxy-D-glucose and 2-deoxy-D-glucose 6 phosphate in rat adipocytes was found not to affect the steady-state distribution of 3-O-methyl-D-glucose although both hexoses share a common transport pathway. This observation argues against a possible effect of 2-deoxy-D-glucose phosphate on the equilibrating nature of the carrier. The results are discussed in light of hypotheses advanced to explain free 2-deoxy-D-glucose accumulation in a variety of cells. PMID- 2923871 TI - Studies on mitochondrial Ca2+-transport and matrix Ca2+ using fura-2-loaded rat heart mitochondria. AB - Rat heart mitochondria were incubated for 5 min at 30 degrees C and at approx. 40 mg protein.ml-1 and in the presence of 10 microM fura-2/AM. This allowed the entrapment of free fura-2 within the mitochondrial matrix and its use as a probe for Ca2+, but without affecting the apparent viability of the mitochondria. Parallel measurements of the activities of the intramitochondrial Ca2+-sensitive enzymes, pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase, allowed an assessment of their sensitivity to measured free Ca2+ within intact mitochondria incubated under different conditions; the enzymes responded to matrix Ca2+ over the approximate range 0.02-2 microM with half-maximal effects at about 0.3-0.6 microM Ca2+. Effectors of Ca2+-transport across the inner membrane (e.g., Na+, Mg2+, Ruthenium red, spermine) did not appear to affect these ranges, but did bring about expected changes in Ca2+ distribution across this membrane. Significantly, when mitochondria were incubated in the presence of physiological concentrations of both Na+ and Mg2+, and at low extramitochondrial Ca2+ (less than 400 nM), there was a gradient of Ca2+ (in:out) of less than unity; at higher extramitochondrial [Ca2+] (but still within the physiological range) the gradient was greater than unity indicating a highly cooperative nature of transmission of the Ca2+ signal into the matrix under such conditions. PMID- 2923872 TI - Ultrastructural localisation of creatine kinase activity in the contact sites between inner and outer mitochondrial membranes of rat myocardium. AB - The mitochondrial isoenzyme of creatine kinase, together with the ADP/ATP translocase, most probably belongs to a functional multi-enzyme complex located on the inner mitochondrial membrane. The outer membrane is a necessary constituent of this microcompartment. On the other hand, electron microscopic visualisation demonstrated the formation of contact sites between inner and outer mitochondrial membranes as a reaction to variations of the energy metabolism. In search for a possible correlation between these biochemical and morphological phenomena, rat myocardia were brought into the required energy state by stimulation through catecholaminergic mechanisms or adjusted perfusion with amytal. Subsequently, creatine kinase was cytochemically localised. Creatine kinase activity is demonstrated in membrane contacts between inner and outer mitochondrial membranes. The extent of contact sites and creatine kinase activity depends on the metabolic state as shown by morphometric analysis of the surface density of cytochemical reaction product. This surface density diminishes drastically after inhibiting the metabolic activity with amytal. It is concluded that these contact sites are dynamic micro-environments in which the active site of creatine kinase, oxidative phosphorylation and ADP/ATP transport interact during basal and stimulated metabolism. PMID- 2923873 TI - The role of chloride ions on the transport of glycine in plasma membrane vesicles from glial cells. AB - The high-affinity transport system for glycine in plasma membrane vesicles from C6 glioma cells is dependent on Na+ and also on the presence of Cl- in the incubation medium. This anion requirement is relatively specific for Cl-, since other anions are also capable of stimulating the glycine transport in the following order of decreasing efficacy: Cl- greater than Br- greater than SCN- congruent to I- greater than NO3- greater than F-. Chloride ions raise the Vmax for transport and, to a lesser extent, act on the Km. The data provided by direct measurements of the coupling of sodium and chloride to the transport of glycine by using a kinetic approach suggest a stoichiometry for the translocation cycle catalyzed by the glycine transporter of two sodium ions and one chloride ion per glycine zwitterion. PMID- 2923874 TI - A refined method for the photoaffinity labelling of the nitrobenzylthioinosine sensitive nucleoside transport protein: application to cell membranes of calf lung tissue. AB - A refined method for the photoaffinity labelling of the NBI-sensitive nucleoside transport protein is described. It involves the use of low concentrations of the photolabile probe [3H]nitrobenzylthioinosine ([3H]NBI), whereas the usual inclusion of dithiothreitol in the protocol is omitted. The method was successfully applied to cell membranes of calf lung tissue, which was shown to be a rich source of this physiologically important protein with all the characteristics (both in membrane bound and solubilized form) known from similar proteins on other cell types. Specific covalent incorporation of radioactivity appeared to be pH independent. SDS-polyacrylamide gel electrophoresis revealed a specifically labelled protein with an apparent molecular weight of 55 kDa. PMID- 2923875 TI - Interaction of protein kinase C with chromaffin granule membranes: effects of Ca2+, phorbol esters and temperature reveal differences in the properties of the association and dissociation events. AB - Interaction of protein kinase C with chromaffin granule membranes has been studied as a means of investigating the translocation of protein kinase C from cytosol to intracellular membrane surfaces, which is believed to occur during secretion. Protein kinase C in an adrenal medullary soluble fraction was found to bind reversibly to granule membranes in a Ca2+-dependent fashion. Association and dissociation events were sensitive to Ca2+ concentrations in the low micromolar range, and the Ca2+ sensitivity of both processes was increased when the membranes had been preincubated with the protein kinase C-activating phorbol ester, 4 beta-phorbol 12-myristate 13-acetate (TPA). Binding of protein kinase C to granule membranes occurred at 0 and 37 degrees C, irrespective of whether the membranes had been preincubated with TPA. However, dissociation of protein kinase C from granule membranes that had been preincubated with TPA occurred only at 37 degrees C and not at 0 degree C, even though dissociation of the enzyme from membranes which had not been preincubated with TPA would occur at both 37 and 0 degrees C. These effects of TPA were not reproduced by 4 alpha-phorbol 12,13 didecanoate (4 alpha PDD), a phorbol ester which does not activate protein kinase C. Soluble protein kinase C activity also associated with chromaffin granules in a Ca2+-dependent manner in an adrenal medullary homogenate, indicating that granules can compete with other intracellular membranes for the binding of protein kinase C. Results obtained with this model system differ from other systems where the interaction of protein kinase C with plasma membranes has been studied and have general implications for studies performed on the translocation of protein kinase C in intact cells and for the role of protein kinase C in stimulus-secretion coupling in the chromaffin cell. PMID- 2923876 TI - Dietary triacylglycerol modulates sodium-dependent D-glucose transport, fluidity and fatty acid composition of rat small intestinal brush-border membrane. AB - Rats were maintained on nutritionally complete diets enriched in unsaturated (menhaden fish oil) or saturated (butter fat) triacylglycerols. After 4 weeks, the animals were killed, proximal small intestinal brush-border membranes were prepared, and examined and compared with respect to their lipid composition, molecular species of phosphatidylcholine, lipid fluidity and sodium-dependent D glucose transport. Membranes prepared from the two dietary groups were found to possess similar ratios of cholesterol/phospholipid (mol/mol), sphingomyelin/phosphatidylcholine (mol/mol), and protein/lipid (w/w). In contrast to these findings, however, striking differences were noted in the total fatty acid compositions of these membranes. Plasma membranes prepared from animals fed the fish oil diet possessed higher percentages of saturated fatty acids as well as (n - 3) unsaturated fatty acids and lower percentages of monounsaturated and (n - 6) unsaturated fatty acids than those prepared from animals fed the butter fat diet. Analysis of the molecular species of phosphatidylcholine by HPLC, moreover, revealed that membranes from rats fed fish oil had higher levels of 16:0-20:5, 16:0-22:6 and 18:0-20:5 and lower levels of 18:0-18:2 and 16:0-18:1 than their butter fat counterparts. As assessed by steady-state fluorescence polarization, differential polarized phase fluorometric and excimer/monomer fluorescence intensity techniques using various fluorophores, the lipid fluidity of membranes from rats fed fish oil was also found to be significantly lower compared to membranes from rats fed butter fat. Finally, comparison of the kinetic parameters of Na+-dependent D-glucose transport revealed that fish oil membrane vesicles had a higher maximum velocity (Vmax) than butter fat membrane vesicles but a similar Km for glucose. PMID- 2923877 TI - Alteration of sodium transport by the choroid plexus with amiloride. AB - Cerebrospinal fluid (CSF) production results from active transport of Na+ from blood to CSF, which is followed by H2O and anions. Amiloride reduces Na+ movement in epithelial tissues. To ascertain if amiloride alters transport of Na+ in the choroid plexus, the drug was administered either i.p. to male Sprague-Dawley rats that were bilaterally nephrectomized to determine in vivo effects, or added to artificial CSF to incubate the choroid plexus in vitro. Choroid cell [Na+] was reduced after amiloride treatment both in vivo and in vitro. In addition, the rate of 22Na uptake into the CSF and choroid plexus (CP) was decreased after amiloride. Alterations in choroid cell [Na+] and 22Na penetration into CSF and CP occurred at relatively high doses of drug (1 mumol/ml, in vitro and 100 micrograms/g in vivo), but lower doses were less effective (0.1 mumol/ml in vitro and 10 micrograms/g in vivo). It is concluded that the effects of amiloride on Na+ distribution and transport in the CP are due to inhibition of basolateral Na+ H+ exchange. PMID- 2923878 TI - Inhibition of inorganic anion transport across the human red blood cell membrane by chloride-dependent association of dipyridamole with a stilbene disulfonate binding site on the band 3 protein. AB - The inhibition of inorganic anion transport by dipyridamole (2,6 bis(diethanolamino)-4,8-dipiperidinopyrimido[5,4-d] pyrimidine) takes place only in the presence of Cl-, other halides, nitrate or bicarbonate. At any given dipyridamole concentration, the anion flux relative to the flux in the absence of dipyridamole follows the equation: Jrel = (1 + alpha 2[Cl-])/(1 + alpha 4[Cl-]) where alpha 2 and alpha 4 are independent of [Cl-] but dependent on dipyridamole concentration. At high [Cl-] the flux approaches alpha 2/alpha 4, which decreases with increasing dipyridamole concentration. Even when both [Cl-] and dipyridamole concentration assume large values, a small residual flux remains. The equation can be deduced on the assumption that Cl- binding allosterically increases the affinity for dipyridamole binding to band 3 and that the bound dipyridamole produces a non-competitive inhibition of sulfate transport. The mass-law constants for the binding of Cl- and dipyridamole to their respective-binding sites are about 24 mM and 1.5 microM, respectively (pH 6.9, 26 degrees C). Dipyridamole binding leads to a displacement of 4,4'-dibenzoylstilbene-2,2' disulfonate (DBDS) from the stilbenedisulfonate binding site of band 3. The effect can be predicted quantitatively on the assumption that the Cl- -promoted dipyridamole binding leads to a competitive replacement of the stilbenedisulfonates. For the calculations, the same mass-law constants for binding of Cl- and dipyridamole can be used that were derived from the kinetic studies on Cl- -promoted anion transport inhibition. The newly described Cl- binding site is highly selective with respect to Cl- and other monovalent anion species. There is little competition with SO4(2-), indicating that Cl- binding involves other than purely electrostative forces. The affinity of the binding site to Cl- does not change over the pH range 6.0-7.5. Dipyridamole binds only in its deprotonated state. Binding of the deprotonated dipyridamole is pH independent over the same range as Cl- binding. PMID- 2923879 TI - Phase behaviour of mixtures of lipid X with phosphatidylcholine and phosphatidylethanolamine. AB - The effect of increasing concentrations of lipid X (2,3-bis(3-hydroxymyristoyl) alpha-D-glucosamine 1-phosphate) on the phase behaviour of EPC (egg phosphatidylcholine) and EPE (egg phosphatidylethanolamine) is studied at a pH greater than or equal to 7 where lipid X carries one to two negative charges. Small amounts of lipid X (molar ratio approximately 0.01) induce continuous swelling of EPC and EPE bilayers and consequently the formation of large unilamellar vesicles in excess water. In many respects, the effect of lipid X on EPC and EPE bilayers is similar to that of phosphatidic acid. However, lipid X/EPC mixtures form micelles in excess lipid X whereas mixtures of phosphatidic acid/EPC vesiculate at all ratios. The same is true for lipid X/EPE mixtures. Small unilamellar vesicles of an average diameter of 40 nm form spontaneously upon dispersion of a dry lipid X/EPE film (molar ratio = 10). Unsonicated dispersions of lipid X/EPC (molar ratio = 1) are subjected to pH-jump treatment which involves raising of the pH to 11-12 and subsequent lowering of the pH to between 7.5 and 8.5. Such a treatment has little effect on the vesicle size and size distribution as compared to a control dispersion at pH 8.2. The mean size is determined to be 92 +/- 60 nm. Electron micrographs of freeze-fractured samples of lipid X/EPC (molar ratio = 1) reveal the presence of mainly micelles at pH 12. Upon lowering the pH to neutrality these micelles become unstable and aggregate/fuse rapidly to unilamellar vesicles (average diameter 95 +/- 40 nm). Sonication of equimolar mixtures of lipid X and EPC at pH 7 yields small unilamellar vesicles of a diameter of 20-25 nm as well as mixed micelles of a size between 15 and 17 nm. This behaviour is again different from that of mixed EPC/phosphatidic acid dispersions which form small unilamellar vesicles. The presence of lipid X in such mixtures does not prevent the aggregation/fusion to larger vesicles during freezing of the dispersion. As with pure EPC bilayers, stabilization is, however, achieved in the presence of 10% sucrose. This indicates that the covalently bonded glucosamine group of lipid X cannot substitute water of hydration in neighbouring EPC molecules. PMID- 2923880 TI - The polymorphic phase behavior of dielaidoylphosphatidylethanolamine. Effect of n alkanols. AB - The polymorphic phase behavior of dielaidoylphosphatidylethanolamine (DEPE) has been investigated using spectrophotometry and 31P nuclear magnetic resonance (NMR). It has been demonstrated that the bilayer to inverted hexagonal phase transition can be observed by spectrophotometry. The effects of the methanol, ethanol, and propanol on both the gel to liquid crystal transition and the bilayer to inverted hexagonal transition were investigated by spectrophotometry. It was shown that these alcohols shift the gel to liquid-crystalline phase transition to lower temperature, whereas the bilayer to inverted hexagonal phase transition is shifted to higher temperatures by these alcohols. The structural transition between the bilayer and inverted hexagonal phase of pure DEPE was also investigated by 31P-NMR. PMID- 2923881 TI - Intermediary structures during membrane fusion as observed by cryo-electron microscopy. AB - Lipidic phases, containing 'lipidic particles' (dioleoylphosphatidylethanolamine/cholesterol/dioleoylphosphatidylcho lin e and cardiolipin/dimyristoylphosphatidylcholine in the presence of Ca2+) have been investigated by preparing thin films from a suspension of sonicated vesicles. These thin films were vitrified and observed 'directly' by cryo-electron microscopy in their hydrated form. The thin films show various fusion products and fusion intermediates such as lipidic particles. PMID- 2923882 TI - Effects of cholesteryl esters on the accessibility of LH/hCG receptors and membrane lipid fluidity in rat testes. AB - Incubation of rat testicular membranes with cholesteryl hemisuccinate resulted in an increase in both membrane lipid microviscosity and 125I-labelled hCG specific binding. The purpose of this investigation was to establish which functional groups of cholesteryl hemisuccinate are important for the stimulatory effects. The data obtained showed that only esters of cholesterol with dicarboxylic acids, not those of monocarboxylic acids, increase the accessibility of LH/hCG receptors and membrane rigidity. Experiments with cholesteryl sulfates showed that there are polar groups on C3 carbon of cholesterol having no stimulatory effect on receptors, although an increase in membrane rigidity occurred. The side-chain of cholesterol is important for the stimulatory action. Androstenolone hemisuccinate was ineffective in this respect. On the other hand, partially modified side chains (hemisuccinates of beta-sitosterol and stigmasterol) did not result in a marked reduction of the stimulatory action. The carboxyl group of cholesteryl hemisuccinate must be 'free': its esterification abolishes the stimulatory effect of cholesteryl hemisuccinate on both the LH/hCG receptor and membrane microviscosity. These results suggest that an intact carboxyl group of ester and the side-chain of cholesterol are indispensable for the stimulatory effect of cholesteryl hemisuccinate on the accessibility of LH/hCG receptors. PMID- 2923883 TI - Saturable and unsaturable binding of a volatile anesthetic enflurane with model lipid vesicle membranes. AB - Presence of specific receptors for volatile anesthetics has recently been proposed (Evers, A.S. et al. (1987) Nature 328, 157-160) by a finding that halothane uptake by the rat brain was characterized, in part, by saturable binding. We report here that volatile anesthetics bind model lipid membranes also with saturable and unsaturable kinetics. Binding of enflurane to dipalmitoylphosphatidylcholine vesicle membranes was measured by gas chromatography. At low anesthetic concentrations, comparable to the clinical level, the interaction was saturable. After reaching a temporary saturation, a sudden increase in the anesthetic binding to the membrane occurred, when the anesthetic concentration in the aqueous phase exceeded 2.7 mM, or 6.3 x 10(-2) atm partial pressure in the gas phase in equilibrium with the aqueous phase. The secondary binding was linear to the aqueous anesthetic concentrations and was unsaturable to the limit of this study. We also found that enflurane self aggregated in water above 4 mM. When the aqueous concentration exceeded 6 mM, the aggregation number was about 8. We conclude that the saturable binding indicates adsorption onto the vesicle surface, and the unsaturable binding indicates multilayer stacking of the enflurane molecules, where the initially adsorbed molecules provide the binding sites to the succeeding molecules according to the multilayer condensation kinetics. The tendency of enflurane to self-aggregate in water promotes the multilayer stacking at the surface of the membrane. PMID- 2923884 TI - The role of sulfhydryl groups in sulfobromophthalein transport in rat liver plasma membrane vesicles. AB - Sulfobromophthalein (BSP) electrogenic transport activity in a plasma membrane vesicle preparation from rat liver is shown to depend on free sulfhydryl groups. These are organized in two classes, one of which does not react with the sulfhydryl group reagent 5,5'-dithiobis(2-nitrobenzoate). The two classes appear to be involved in BSP transport independently. However, reactivity of one class can be shown to be affected by alkylation of the other. Hence, it is concluded that both classes are located on the same carrier system, which previous research has established to be the integral sinusoidal membrane protein bilitranslocase. PMID- 2923885 TI - 'Slow' K+-stimulated Ca2+ influx is mediated by Na+-Ca2+ exchange: a pharmacological study. AB - K+-stimulated 45Ca2+ influx was measured in rat brain presynaptic nerve terminals that were predepolarized in a K+-rich solution for 15 s prior to addition of 45Ca2+. This 'slow' Ca2+ influx was compared to influx stimulated by Na+ removal, presumably mediated by Na+-Ca2+ exchange. The K+-stimulated Ca2+ influx in predepolarized synaptosomes, and the Na+-removal-dependent Ca2+ influx were both saturating functions of the external Ca2+ concentration; and both were half saturated at 0.3 mM Ca2+. Both were reduced about 50% by 20 microM Hg2+, 20 microM Cu2+ or 0.45 mM Mn2+. Neither the K+-stimulated nor the Na+-removal dependent Ca2+ influx was inhibited by 1 microM Cd2+, La3+ or Pb2+, treatments that almost completely inhibited K+-stimulated Ca2+ influx in synaptosomes that were not predepolarized. The relative permeabilities of K+-stimulated Ca2+, Sr2+ or Ba2+ influx in predepolarized synaptosomes (10:3:1) and the corresponding selectivity ratio for Na+-removal-dependent divalent cation uptake (10:2:1) were similar. These results strongly suggest that the K+-stimulated 'slow' Ca2+ influx in predepolarized synaptosomes and the Na+-removal-dependent Ca2+ influx are mediated by a common mechanism, the Na+-Ca2+ exchanger. PMID- 2923886 TI - Membrane-phorbol ester interactions monitored by circular dichroism. AB - The interaction of phorbol 12,13-dibutyrate (PDBu), 12-O-retinoylphorbol 13 acetate (RPA) and 12-O-tetradecanoylphorbol 13-acetate (TPA) with L-alpha phosphatidylserine-containing small unilamellar vesicles or erythrocyte ghosts was monitored by circular dichroism (CD). No change in the CD spectra of PDBu was observed upon binding, while RPA and TPA spectra were slowly affected by the interaction. The changes in RPA and TPA spectra were assigned to the embedding of these molecules in the membrane bilayers. In the presence of 10(8) cells/ml, after one minute incubation, about 2 to 5% of the amount of phorbol ester added is embedded in the membrane. It is suggested that either phorbol esters entering the membrane is not a prerequisite for protein kinase C activation or the amount of phorbol esters necessary to activate protein kinase C is very small. PMID- 2923887 TI - Detection and characterization of anionic polypeptide fraction binding sites in rat liver plasma membranes and cultured hepatocytes. AB - The binding of human 125I-labeled 'anionic polypeptidic fraction' (APF) to purified rat liver plasma membranes was studied. The dissociation constant for this binding was 3.0 micrograms protein/mg membrane protein. Binding was competitively inhibited by unlabeled human APF, but not by human LDL (low density lipoproteins). When unlabeled HDL3 was added, binding of labeled APF was competitively reduced to a level between that of unlabeled APF and unlabeled LDL. Experiments with cultured rat hepatocytes confirmed those obtained with liver membranes and suggested the presence in rat liver of saturable APF-binding sites which seem to be specific for APF. The physiologic significance of these APF binding sites is discussed in relation to the fate of cholesterol in the liver. PMID- 2923888 TI - Persistence at low temperature of the P beta' ripple in dipalmitoylphosphatidylcholine multilamellar vesicles containing either glycosphingolipids or cholesterol. AB - The disappearance and reappearance of the P beta' ripple in multilamellar liposomes of dipalmitoylphosphatidylcholine (DPPC) has been examined by freeze etch electron microscopy. The presence of less than 10 mol% of various glycosphingolipids or cholesterol in the liposomes markedly increases the time required for ripple disappearance when the vesicles are cooled from 38 degrees C to 30 degrees C, as compared to the pure phospholipid. Once the ripples have begun to disappear in the two-component vesicles, they do not uniformly reappear until the system is heated above the main transition of DPPC and allowed to cool into the pretransition region. These results suggest that the long time for ripple disappearance in the two-component systems reflects a slow molecular reorganization process which occurs when the systems are forced to change from the P beta' gel to the L beta' gel by a temperature downshift. PMID- 2923889 TI - Effect of the asymmetric Ca2+ distribution on the bilayer properties of phosphatidylcholine-sonicated vesicles. AB - The incorporation of Ca2+ in the inner volume of egg phosphatidylcholine vesicles increases the fluorescence anisotropy of a diphenylhexatriene probe. This increase is higher than for Na+ at the same normality. An effect of the same magnitude is induced by Ca2+ when using binary lipid mixture (dioleoylphosphatidylcholine and dipalmitoylphosphatidylcholine) as long as the mixture is maintained below the phase-transition temperature of the saturated species. The influence of Ca2+ may be explained by an asymmetric distribution of the saturated and unsaturated lipids between the internal and the external monolayers. PMID- 2923890 TI - Membrane potential measurements in isolated rat liver plasma membrane vesicles: effect of transmembrane ion concentration gradients. AB - In isolated basolateral and canalicular rat liver plasma membrane vesicles the membrane potential (measured with DiS-C2 (5] varied with transmembrane concentration gradients of Na+, K+ and Cl- revealing the following ion permeabilities: basolateral vesicles: PNa/PK: 0.76, PCl/PK: 0.45 and canalicular vesicles: PNa/PK: 0.69, PCl/PK: 0.56. The data indicate a permselectivity of PK greater than PNa greater than PCl for both membranes. PMID- 2923891 TI - Reversible and irreversible rotating field-induced membrane modifications. AB - We analyse the charge distribution as submitted by additionally induced transmembrane potentials in rotating electric fields. In contrast to d.c. and a.c. fields, in rotating fields the induced peak potential differences across the membrane systems are phase shifted with respect both to each other and to the external field vector. These phase differences are strongly frequency-dependent but were also influenced by the electrical properties of both the cell and the surrounding medium. We extend our investigation up to the non-linear field strength range of electrorotation and found reversible and irreversible changes in the rotational behavior of several cells. The most convenient variables for describing non-linear electrorotation are the characteristic frequency (fc1) and the corresponding angular velocity (omega c) of the cells. With increasing field strength the observed rotational behavior becomes more and more irreversible and finally rupture of the membrane occurs. PMID- 2923892 TI - Regulation of glucose transport activity and expression of glucose transporter mRNA by serum, growth factors and phorbol ester in quiescent mouse fibroblasts. AB - We have investigated the effects of growth factors such as serum, platelet derived growth factor (PDGF) and fibroblast growth factor (FGF) on glucose transport activity in quiescent mouse Swiss 3T3 cells. DNA synthesis was synchronously induced by either calf serum, or platelet-poor plasma in combination with PDGF or FGF. Early stimulation of glucose transport in the quiescent cells was also caused by serum, or by either PDGF or FGF. The time courses for the stimulation of transport were identical for serum, PDGF and FGF, and the stimulated uptake in each case was associated with a 5-6-fold increase in Vmax. There were no detectable changes in apparent Km. Expression of glucose transporter mRNA was also enhanced by these growth factors. By contrast, EGF, insulin and platelet-poor plasma had little effect on glucose transport and transporter-gene expression, although uridine uptake was enhanced by all of these growth factors. These results suggest that cell cycle-dependent stimulation of glucose transport and expression of the transporter mRNA are regulated by a specific class of growth factors such as PDGF and FGF. The tumor promoter phorbol 12-myristate 13-acetate (PMA) also stimulated glucose transport and expression of transporter mRNA in quiescent 3T3 cells. These stimulations were absent in PMA pretreated cells. However, serum, PDGF and FGF were able to stimulate glucose transport as well as expression of the transporter mRNA in PMA-pretreated cells, suggesting that there are at least two independent pathways for regulating glucose transport and glucose transporter mRNA level in quiescent fibroblasts. PMID- 2923893 TI - Egg jelly triggers a calcium influx which inactivates and is inhibited by calmodulin antagonists in the sea urchin sperm. AB - Sea urchin sperm must undergo the acrosome reaction to fertilize eggs. The natural inducer of this reaction is the most external coat of the egg, named 'jelly'. The ionic composition of the extracellular and intracellular media and the permeability properties of the sperm plasma membrane are fundamental in this reaction. As Ca2+ is required for the acrosome reaction to occur, its intracellular concentration ([Ca2+]i) was measured with fura-2. In 10 mM Ca2+, egg jelly induced the acrosome reaction and an increase in [Ca2+]i that lasted for several minutes. However, at 0.5 or 2 mM Ca2+, it became evident that the Ca2+-influx pathway activated by jelly opened only for a few seconds; this prevented both the full increase in [Ca2+]i and the acrosome reaction even after the concentration of Ca2+ was raised to 10 mM. In the presence of jelly, the time this permeability pathway remained open was inversely related to the extracellular concentration of Ca2+ ([ Ca2+]e). Using Bisoxonol (a permeant fluorescent membrane potential probe), it was found that the jelly-induced depolarization depended on [Ca2+]e and was proportional to the increase in [Ca2+]i. Since [Ca2+]i could affect the jelly-induced Ca2+ influx through calmodulin, two of its antagonists, trifluoperazine and W-7, were tested. Both compounds blocked the acrosome reaction by inhibiting the jelly-induced increase in [Ca2+]i. W-5 at the same concentration had no effect. The results suggest that one of the jelly-activated Ca2+-influx pathways, probably a channel, is the target of the calmodulin antagonists. PMID- 2923894 TI - Segregation of anionic lipophiles in bilayers monitored by binding of cationic dye NK-529. AB - Fluorescence emission properties of a cationic indodicarbocyanine dye, NK-529, bound to anionic and zwitterionic vesicles, are examined under a variety of conditions to monitor lateral distribution of anionic amphiphiles in bilayers as a function of their phase properties. The change in the fluorescence properties of NK-529 arises from the binding of the dye to the bilayer that is dominated by ionic interactions when possible, as well as from the self-quenching of the dye bound to bilayers when the surface density of the dye is high. The binding affinity of the dye to anionic interfaces is more than 100-fold higher compared to that in zwitterionic bilayers. The limiting phospholipid/dye ratio in anionic bilayers at low vesicle concentrations is about 3. Thus the density of the bound dye in anionic bilayers can be more than 40-fold higher than that in zwitterionic bilayers, and therefore under such conditions the bound dye is completely self quenched in vesicles or micelles of anionic phospholipids. The change in the fluorescence emission intensity on incorporation of anionic amphiphiles in zwitterionic bilayers is used to monitor segregation of the anionic amphiphiles. The organizational features of bilayers that cause a change in the fluorescence properties of bound NK-529 show that the lateral distribution of anionic amphiphiles is appreciably influenced not only by the mole fraction of the amphiphile but also in the presence of other additives, and by the gel-fluid thermotropic transition. As shown in the following paper, the fluorescence changes related to self-quenching in anionic bilayers containing NK-529 can be used to understand the organizational changes that occur during the course of interfacial catalysis by phospholipase A2 on zwitterionic bilayers. PMID- 2923895 TI - Binding of phospholipase A2 to zwitterionic bilayers is promoted by lateral segregation of anionic amphiphiles. AB - Catalytic action of phospholipase A2 is appreciably influenced by the organization and dynamics of bilayers of glycerophosphocholines (Apitz-Castro et al. (1988) Biochim. Biophys. Acta 688, 341-348). However, such effects of the quality of the interface are not observed with bilayers of glycerophosphoryl methanol and other anionic phospholipids (Jain et al. (1986) Biochim. Biophys. Acta 860, 435-447). Such differences between the catalytic susceptibility of zwitterionic versus anionic bilayers are due to a large difference in the affinity of the enzyme for these interfaces. Binding to phospholipase A2 to zwitterionic interfaces can be promoted in the presence of certain anionic additives. For example in the pre-steady-state phase of hydrolysis, segregation of the nacently produced products of hydrolysis could promote binding of phospholipase A2 to regions of higher anionic charge density in the zwitterionic interface. In this paper we show that the dynamics of segregation of the nacently produced products of hydrolysis in zwitterionic bilayers can be readily followed by monitoring the fluorescence intensity of the cationic dye NK-529 (Yu and Jain (1989) Biochim. Biophys. Acta 980, 15-22). The fluorescence emission characteristics of NK-529 change appreciably due to self-quenching of the bound dye molecules as the fatty acid molecules segregate in the bilayer. The kinetics of segregation of fatty acids during the course of hydrolysis of bilayers of zwitterionic phospholipids by phospholipase A2 exhibits an unequivocal correlation with a variety of phenomena that are observed during the transition from the pre-steady-state phase to the steady-state phase of hydrolysis in the reaction progress curves as a function of temperature and in the presence of lipophilic additives. PMID- 2923896 TI - Influence of sodium conductances on platelet activation. AB - The effects of extracellular Na+ and tetrodotoxin on resting membrane potential, cytosolic free Ca2+ levels and aggregation of human platelets have been studied. Neither the decrease in extracellular Na+-concentration (from 140 mmol/l to 0 mmol/l) nor the addition of tetrodotoxin (10(-7) to 10(-5) mol/l) modified the platelet membrane potential. Zero extracellular Na+ concentration or the presence of tetrodotoxin in the medium inhibited platelet aggregation; however, K+ depolarized platelets showed an unchanged aggregation induced by ADP or thrombin in media with zero or low extracellular Na+ concentrations or in the presence of tetrodotoxin. Moreover, zero extracellular Na+ concentration or tetrodotoxin inhibited calcium mobilization in platelets during activation induced by thrombin. Hence, voltage-dependent activation linked to Na+ influx appears to be necessary for ADP- and thrombin-induced platelet aggregation under control conditions. Mechanisms for the role of Na+ conductances in platelet function are discussed. PMID- 2923897 TI - Hydrogen bonding between anhydrous cholesterol and phosphatidylcholines: an infrared spectroscopic study. AB - Fourier transform infrared spectroscopy performed with a high pressure diamond anvil cell was used to study hydrogen bonding between anhydrous phosphatidylcholines and cholesterol at the molar ratio 4:1. The hydroxyl group of cholesterol which acts as a proton donor, engages in strong hydrogen bonding to the sn-2 chain carbonyl group of DMPC, DPPC and HPPC and in weak hydrogen bonding to the phosphate group of all these phospholipids. No evidence of hydrogen bonding between cholesterol and the sn-1 chain carbonyl group of DMPC and DPPC was found. From a comparison of the relative hydrogen-bond strengths between cholesterol or water and the sn-2 chain carbonyl and phosphate groups of all these phospholipids, it is predicted that in aqueous dispersions of cholesterol containing phospholipids, the hydrogen bond of cholesterol to the phosphate group would be replaced by that of water, while the hydrogen bond of cholesterol to the sn-2 chain carbonyl group would remain intact. PMID- 2923898 TI - An infrared spectroscopic study of the thermotropic phase behavior of phosphatidylcholines containing omega-cyclohexyl fatty acyl chains. AB - The thermotropic phase behavior of an odd- and an even-numbered member of the homologous series of 1,2-di-omega-cyclohexylphosphatidylcholines was studied using Fourier transform infrared spectroscopy. The results obtained indicate that the pronounced discontinuities in the behavior of the odd- and even-numbered homologues observed by differential scanning calorimetry can be attributed to differences in the organization of their respective gel states. The single phase transition exhibited by the odd-numbered compounds upon heating is shown by infrared spectroscopy to be a direct transition from a condensed, subgel-like phase (Lc phase) to the liquid-crystalline state (L alpha phase). In contrast, the multiple transitions exhibited by the even-numbered homologues are shown to be due to the initial conversion of an L beta-like phase to a more loosely packed gel phase, followed by the acyl chain-melting transition. Moreover, the major changes in the interaction between the acyl chains, and in the organization of the interfacial region of the bilayers formed by the even-numbered homologue, occur at temperatures below that of the onset of the chain-melting phase transition. The infrared spectroscopic changes observed also suggest that above the chain-melting transition, the odd- and even-numbered homologues form similar liquid-crystalline phases that are more 'ordered' than those of normal saturated straight-chain phosphatidylcholines. Most likely this is because the large size and the intrinsic rigidity of the omega-cyclohexyl group reduces the conformational disorder of the liquid-crystalline state by 'dampening' all acyl chain motions. The formation of a relatively ordered liquid-crystalline state may be the critical property exploited by the thermoacidophylic organisms in which omega-cyclohexyl fatty acids naturally occur. PMID- 2923899 TI - Transport of sodium into apical membrane vesicles prepared from fetal sheep alveolar type II cells. AB - A method is described for isolating apical plasma membrane vesicles from fetal alveolar type II cells. The procedure yields purified apical membranes which are enriched 24-fold with the brush-border enzyme marker, alkaline phosphatase. Contamination of this fraction by basolateral membranes and organelles is minimal. Evidence for transport of Na+ into an intravesicular space is demonstrated by: (1) time-dependent uptake of Na+ with release of accumulated Na+ by treatment with detergent; (2) a linear inverse correlation between Na+ uptake and medium osmolarity. In addition, Na+ uptake is shown to be anion dependent (SCN- greater than Cl- greater than gluconate-) and sensitive to amiloride inhibition at a concentration of 1 mM. PMID- 2923900 TI - The solubilization and morphological change of human platelets in various detergents. AB - The solubilization of human gel-filtered platelets by octyl glucoside, Triton X 100, dodecylsulfate, and deoxycholate was compared from the analysis of (1) cell lysis, (2) marker leakiness, and (3) component solubility. These analyses all revealed that the effect of detergent concentration on the solubilization of platelets by these detergents was exerted in three stages, i.e., the prelytic, lytic, and complete platelet-lysis stages. These analyses also indicated several differences among platelets in these detergents. (i) The ratio of the platelet saturation concentration (PSC) to critical micellar concentration (CMC) was about 1/2 for octyl glucoside. Triton X-100 and dodecylsulfate, while it was close to 1 for deoxycholate. (ii) Platelets in octyl glucoside. Triton X-100, and dodecylsulfate all showed parallel curves in cell lysis, protein solubilization and marker leakiness, while the platelet lysis in deoxycholate was identical to the phospholipid solubilization. (iii) The solubility curves of various components in Triton X-100 and deoxycholate were parallel. However, the solubility of cholesterol in octyl glucoside was lower than that of protein and phospholipid. In dodecylsulfate, the solubility of phospholipid and cholesterol was very low in comparison with that of protein. In addition, morphological studies using scanning electron microscopy (scanning EM) revealed that the solubilization by octyl glucoside or Triton X-100 might occur via membrane area expansion. On the other hand, the solubilization by dodecylsulfate or deoxycholate showed membrane vesiculation prior to cell lysis. Moreover, in the prelytic stage, the morphological change in platelets in octyl glucoside showed only concentration dependence by swelling to an ellipsoid and then to a sphere. However, the morphological change in platelets in the other three detergents was dependent not only on the detergent concentration but also on prolonged incubation. Specifically, in Triton X-100, the cells initially changed to spiculate discs and then reached their final shape as swollen discs with surface invagination. In dodecylsulfate and deoxycholate the morphological changes were almost the same. The cell initially deformed in shape to a spiculate disc and finally to a stretched-out flat form. The results are discussed according to the bilayer couple hypothesis. Also, in the prelytic stage, these detergents caused inhibition of the response of platelets to collagen and ADP-fibrinogen. PMID- 2923901 TI - Chain-length dependence of n-alkane solubility in phosphatidylcholine bilayers: a 2H-NMR study. AB - Phosphatidylcholine bilayer membranes containing 2H-labelled n-alkanes have been studied by 2H-NMR as a model system for the investigation of molecular theories of general anesthesia. The solubilities of n-alkanes in lipid bilayers have been determined by measurement of the relative intensities of a powder pattern signal arising from orientationally ordered, membrane-soluble alkane and a sharp signal in the 2H-NMR spectrum resulting from isotropically reorienting alkane. The ordering profiles for the ordered n-alkane as determined from the quadrupole splittings for different segments along the chain are similar to those described earlier for n-hexane, n-octane and n-dodecane, suggesting that the restricted motions undergone by the n-alkanes of chain length from 6 to 19 are basically similar. For this homologous series of n-alkanes, it was found that membrane solubility dropped sharply at an alkane chain length which depended on lipid chain length, degree of unsaturation, cholesterol concentration in the bilayer, and temperature. The results show that the incorporation of n-alkanes in lipid bilayers is a complex function of lipid composition. The implications of these results in relationship to the observed 'cut-off' in anesthetic potency in the n alkane homologous series are discussed. PMID- 2923902 TI - Perturbation of binary phospholipid mixtures by melittin: a fluorescence and raman spectroscopy study. AB - The effect of melittin on different binary mixtures of phospholipids has been studied by polarization of DPH fluorescence in order to determine if melittin can induce phase separation. Since the interaction between lipids and melittin is sensitive to both electrostatic and hydrophobic forces, we have studied the effect of the acyl chain length and of the polar head group of the lipids. In spite of the difference of the chain length between dipalmitoylphosphatidylcholine (DPPC) and distearoylphosphatidylcholine (DSPC), no phase separation occurs in an equimolar mixture of these lipids in presence of melittin. However, when the charged lipid dipalmitoylphosphatidylglycerol (DPPG) is mixed with either DPPC or DSPC, the addition of melittin leads to phase separation. The DSPC/DPPG/melittin system, which shows a very complex thermotropism, has also been studied by Raman spectroscopy using DPPG with deuteriated chains in order to monitor each lipid independently. The results suggest that the higher affinity of melittin for DPPG leads to a partial phase separation. We propose the formation of DPPG-rich domains perturbed by melittin and peptide-free regions enriched in DSPC triggered by the head group charge and chain-length differences. PMID- 2923903 TI - A comparative study of band 3 aggregation in erythrocyte membranes by melittin and other cationic agents. AB - The technique of laser flash-induced transient dichroism has been used to measure the rotational diffusion of eosin-labelled band 3 proteins in erythrocyte ghosts. A retardation in the mobility of band 3, measured subsequent to the addition of a variety of polyvalent cationic species, has been interpreted to reflect aggregation or 'clustering' of the protein in the plane of the membrane. A comparative study is reported between three such aggregators: melittin, polylysine and Zn2+, wherein their respective abilities to induce aggregation have been measured under varying conditions. Unlike that for melittin, band 3 aggregation by polylysine and Zn2+ is shown to be sensitive to proteolytic degradation of the membrane and to the ionic strength of the surrounding medium. Studies with fragments of melittin derived from its chymotryptic cleavage show the hydrophilic C-terminal 20-26 section to possess independent aggregating ability, but also the requirement of the 1-19 hydrophobic section to be attached in order to prevent reversibility by high ionic strength buffers. Melittin is also shown to have a unique ability to aggregate bacteriorhodopsin reconstituted into DMPC vesicles, which is partially retained by its 1-19 but not by its 20-26 fragment. PMID- 2923904 TI - The potential role of human kidney cortex cysteine proteinases in glomerular basement membrane degradation. AB - (1) The degradation of glomerular basement membrane and some of its constituent macromolecules by human kidney lysosomal cysteine proteinases has been investigated. Three cysteine proteinases were extracted from human renal cortex and purified to apparent homogeneity. These proteinases were identified as cathepsins B, H and L principally by their specific activities towards Z-Arg-Arg NHMec, Leu-NNap and Z-Phe-Arg-NHMec, respectively, and their Mr on SDS polyacrylamide gel electrophoresis under reducing conditions. (2) Cathepsins B and L, at acid pH, readily hydrolysed azocasein and degraded both soluble and basement membrane type IV and V collagen, laminin and proteoglycans. Their action on the collagens was temperature-dependent, suggesting that they are only active towards denatured collagen. Cathepsin L was more active in degrading basement membrane collagens than was cathepsin B but qualitatively the action of both proteinases were similar, i.e., at below 32 degrees C the release of an Mr 400,000 hydroxyproline product which at 37 degrees C was readily hydrolysed to small peptides. (3) In contrast, cathepsin H had no action on soluble or insoluble collagens or laminin but did, however, hydrolyse the protein core of 35S-labelled glomerular heparan sulphate-rich proteoglycan. (4) Thus renal cysteine proteinases form a family of enzymes which together are capable of degrading the major macromolecules of the glomerular extracellular matrix. PMID- 2923905 TI - Isolation and characterisation of a neutral proteinase from the canine intervertebral disc. AB - A neutral proteinase of 94 kDa capable of degrading gelatin, canine disc proteoglycan, and L-lysine and L-arginine peptide substrates has been isolated from the greyhound intervertebral disc. Strong inhibition of this proteinase with class-specific inhibitors, such as APMSF, TLCK and benzamidine indicated a 'serine'-type specificity. Metallo, aspartyl- and cysteine proteinase inhibitors were devoid of significant action. Degradation of the resident canine disc proteoglycan monomer by the disc proteinase was shown to occur at the hyaluronic acid binding region, thereby diminishing its ability to aggregate with hyaluronic acid. The hydrodynamic size of the proteoglycan degradation products was only slightly less than that of the intact disc proteoglycan subunits. PMID- 2923906 TI - Laser intensity and wavelength dependence of Rose-Bengal-photosensitized inhibition of red blood cell acetylcholinesterase. AB - The intensity and wavelength-dependence of Rose-Bengal-mediated photoinhibition of red blood cell acetylcholinesterase has been studied. Irradiation of dye membrane suspensions with 308 nm laser excitation resulted in enzyme inhibition almost 50% greater than that obtained with 514 nm laser excitation. Sodium azide and argon purging greatly decreased the photosensitized enzyme inhibition at both wavelengths. Although Rose Bengal photosensitized enzyme inhibition more efficiently upon excitation into Sn (308 nm) than into S1 (514 nm), Stern-Volmer analysis of sodium azide quenching data gave similar quenching efficiencies at both wavelengths. Irradiation of dye-membrane suspensions with increasing intensities (Nd:YAG, 532 nm, 40 ps pulse duration) resulted in a decrease in enzyme inhibition. Saturation of the Rose Bengal fluorescence intensity and light transmission occurred with nearly the same intensity-dependence, suggesting that ground-state depletion occurs at the higher intensities. Our results demonstrate that excitation of a sensitizer into higher-lying excited singlet states can result in enhanced sensitizing efficiency. However, attempts to populate such states in Rose Bengal by sequential two-photon absorption using high intensities resulted only in ground-state depletion. PMID- 2923908 TI - Kinetic properties of derepressible acid phosphatase from the yeast from of Yarrowia lipolytica. AB - (1) An acid phosphatase from depressed cells of the yeast form of Yarrowia lipolytica has been characterized kinetically by studies on specificity, inhibition, rate equation forms and modelling of the enzyme mechanisms. (2) The study on specificity revealed that the acid phosphatase is a rather unspecific phosphohydrolase that has similar activity on several different phosphate esters. A very weak transphosphorylating activity was also detected. (3) Among the reversible inhibitors, phosphate and vanadate were outstanding, whereas EDTA behaved as an activator. (4) v vs. [S] studies with o-carboxyphenyl phosphate as substrate show that the acid phosphatase of Y. lipolytica exhibits non-Michaelian behaviour, a minimum degree of 2:2 being detected for the rate equation in [S]. (5) The inhibition by phosphate and vanadate seems to have the same pattern of partial inhibition with a certain non-competitive nature, 1:1 being the minimum degree of the rate equation detected in (I). PMID- 2923907 TI - Premalignant alterations in rat colonic N1-acetylspermidine levels induced by 1,2 dimethylhydrazine: effects of a high corn oil dietary regimen. AB - Recently, our laboratory has demonstrated that elevations in the levels of N1 acetylspermidine could be detected in the colonic mucosa of rats after administration of 1,2-dimethylhydrazine for 15 weeks, i.e., before the development of colon tumors. Since prior studies have indicated that diets high in fat, particularly unsaturated fat, promote the development of dimethylhydrazine-induced tumors, it was of interest to examine the effect of a corn oil dietary regimen (20% by weight) on colonic N1-acetylspermidine levels in this model of colonic adenocarcinoma. Four groups of rats were used in these studies: chow, chow + carcinogen, corn oil and corn oil + carcinogen. The carcinogen groups received weekly s.c. injections of 1,2-dimethylhydrazine (20 mg/kg body wt) for 15 weeks, while the control groups received diluent. 1 week after the last injection, animals from each group were killed, and their proximal and distal colons were resected, examined and compared with respect to polyamine levels, including N1-acetylspermidine, as well as the activities of ornithine decarboxylase, spermidine N1-acetyltransferase, and polyamine oxidase. In view of previous studies which suggested that N1-acetylspermidine levels may be elevated in the urine of patients with various malignancies, it was also of interest to examine and compare the urinary levels of this acetylated polyamine in animals from each group. The results of these experiments demonstrated that: (1) the levels of N1-acetylspermidine in the distal colonic segment were found to be increased approx. 25 and 80% in the chow + carcinogen and corn oil + carcinogen groups, respectively, compared to their control counterparts; (2) the activities of spermidine N1-acetyltransferase in the distal colonic segments of chow + carcinogen and corn oil + carcinogen animals were increased 1.5- and 2-fold, respectively, compared to control values; (3) dimethylhydrazine administration did not affect the levels of this acetylated polyamine or spermidine N1 acetyltransferase activities in the proximal colon, but, in general, did increase the levels of putrescine and spermidine as well as ornithine decarboxylase activities in both colonic segments of animals fed chow or corn oil diets; and (4) elevated urinary levels of N1-acetylspermidine did not appear to be a reliable 'premalignant' marker in this experimental model of colonic adenocarcinoma. PMID- 2923909 TI - Binding characteristics of a major thyroid hormone metabolite, 3,3',5'-triiodo-L thyronine, to bovine serum albumin as measured by fluorescence. AB - The interaction between a major thyroid hormone metabolite, 3,3',5'-triiodo-L thyronine and bovine serum albumin was investigated by fluorescence measurements. The apparent binding constants were obtained at various pHs assuming the equivalence and independence of the interaction sites on the protein from the fluorescence titration curves. The maximum binding was attained at pH 8.0, and the apparent binding constant was (5.28 +/- 0.13).10(5) M-1 with one binding site per albumin molecule. Thermodynamic parameters were also determined from the van't Hoff plot of the apparent binding constants at pH 7.5. The free energy change, enthalpy change and entropy change were -7.70 +/- 0.09 kcal.mol-1, -4.59 kcal.mol-1 and 10.2 e.u., respectively. PMID- 2923910 TI - Effect of hexachlorobiphenyl on vitamin A homeostasis in the rat. AB - Vitamin A status and turnover were examined in rats that had been exposed to chronic dietary treatment of 3,4,5,3',4',5'-hexachlorobiphenyl (HCB), 1 mg/kg diet. HCB caused hepatic depletion and renal accumulation of vitamin A, and a 1.7 fold increase in the serum retinol concentration. Intravenously administered [3H]retinol bound to retinol binding protein-transthyretin complex (RBP-TTR complex) was used to study the dynamics of circulatory retinol in these rats. In HCB-treated rats, the plasma turnover rate of retinol was increased compared to vitamin A-adequate untreated controls. HCB caused a 50% reduction of total radioactivity in liver, and, except for 0.5 h after the [3H]retinol-RBP-TTR dose, the specific activity of the hepatic retinyl ester pool was greater compared to control rats. The kidneys of HCB-treated rats accumulated radioactivity in the retinyl ester fraction. HCB also caused a 50% reduction in adrenal radioactivity compared with control rats. Urinary and fecal excretion of radioactivity was 3 fold higher in HCB-treated rats as compared to controls. Our findings demonstrate that chronic HCB feeding results in expansion of plasma vitamin A mass, in changes of liver and kidney retinol and retinyl ester pool dynamics and in an increased metabolism of vitamin A. PMID- 2923911 TI - Antiplatelet actions of panaxynol and ginsenosides isolated from ginseng. AB - The antiplatelet effect of panaxynol isolated from the diethyl ether layer was compared with those of ginsenosides from the butanol layer of Panax ginseng. Panaxynol (0.1 mg/ml) inhibited markedly the aggregation of washed platelets induced by collagen, arachidonic acid, ADP, ionophore A23187, PAF and thrombin while ginsenosides had no significant effect on the aggregation but ginsenoside Ro (1 mg/ml) inhibited the ATP release of platelets. Less inhibitory effect of panaxynol was observed in the aggregation of platelet-rich plasma. Thromboxane B2 formation of platelets was inhibited by panaxynol but not by ginsenosides. The antiplatelet effect of panaxynol was dependent on the incubation time and the aggregability of platelets inhibited by panaxynol could not easily be recovered after washing the platelets. In human platelet-rich plasma, panaxynol prevented secondary aggregation and completely blocked ATP release from platelets induced by epinephrine and ADP. Both panaxynol and ginsenoside Rg2 inhibited the rise of intracellular calcium caused by collagen. It is concluded that panaxynol is the most potent antiplatelet agent in ginseng and its mechanism of action is chiefly due to the inhibition of thromboxane formation. PMID- 2923912 TI - Differential expression of alpha and pi isoenzymes of glutathione S-transferase in developing human kidney. AB - Polyclonal antisera to the alpha and pi isoenzymes of glutathione S-transferase have been used in immunohistochemical studies to determine the developmental expression of these isoforms in human kidney. Before 35 weeks of gestation, both isoenzymes were expressed by the collecting tubules and developing nephrons. After this time, expression of the alpha set was restricted to the proximal tubule and that of the pi set to the distal and collecting tubules and the loop of Henle. PMID- 2923913 TI - Administration of D-aspartate increases D-aspartate oxidase activity in mouse liver. AB - Oral administration of D-aspartate to mice for 2 weeks by addition of the amino acid to drinking water produced a nearly 4-fold increase in liver D-aspartate oxidase (EC 1.4.3.1) activity, whereas no increase was induced by L-aspartate administered in the same way. Administration of D-aspartate also produced a small significant increase in the kidney enzyme activity, but L-aspartate administration increased the activity as well. The enzyme activity in the brain and muscle was not affected by administration of either D- or L-aspartate. Intraperitoneal administration of D-aspartate increased the enzyme activity only in the liver, and other compounds tested, including D-glutamate and D-alanine, could not replace D-aspartate. The results indicate a specific relationship between D-aspartate and D-aspartate oxidase and suggest that the amino acid is, in fact, a physiological substrate of the enzyme. PMID- 2923914 TI - Coenzyme non-specific glutamate dehydrogenase from Chlorella pyrenoidosa 82T: electron microscopic studies. AB - The constitutive coenzyme non-specific glutamate dehydrogenase (GDH) from Chlorella pyrenoidosa 82T was purified to homogeneity by column immunoaffinity chromatography and examined by an electron microscope. The enzyme molecule was found to be a hexameric oligomer composed of monomers arranged in three 2-point group symmetry in two layers slightly twisted round the 3-fold axis. The molecule is 8 +/- 1 nm in diameter and 10 +/- 1 nm in height. The enzyme molecules appear both to dissociate into trimers and to associate along the 3-fold axis forming linear aggregates under certain conditions. A tentative model of the Chlorella GDH molecule is proposed, which is very similar to those described for bovine liver GDH and GDH from Clostridium symbiosum. PMID- 2923915 TI - Mucus proteinase inhibitor: a fast-acting inhibitor of leucocyte elastase. AB - Human mucus proteinase inhibitor is a fast-acting inhibitor of human leucocyte elastase (EC 3.4.21.37) and forms a stable, complex with this enzyme. At physiological ionic strength and temperature and in the presence of 10 mg/ml albumin, the kinetic constants characterizing the interaction between elastase and the non-degraded inhibitor are: kass = 6.4.10(6) M-1.s-1, kdiss = 2.3.10(-3) s-1, Ki = 3.10(-10) M. The partially degraded inhibitor isolated by chymotrypsin Sepharose chromatography inhibits elastase with similar efficiency, suggesting that if partial proteolysis of the inhibitor occurs in vivo, the latter may still act as a potent antielastase. Mucus proteinase inhibitor therefore plays a physiological antielastase function in upper respiratory tract secretions, since it inhibits elastase with a delay time of 150 ms and behaves like an irreversible inhibitor. PMID- 2923916 TI - The molecular localization of non-tryptophan chromophores in calf lens crystallins. AB - A single-step separation of calf lens gamma-crystallin into six protein components is described. UV absorption spectra, characterized by the presence of high absorbance in the 240-250 nm and 310-360 nm spectral regions as well as by fluorescence emission above 400 nm, are shown by six components. alpha-, beta and beta S crystallins have been compared with the gamma-fraction for the presence of non-tryptophan fluorescence. The chromophores responsible for this non-tryptophan fluorescence were found to be associated with gamma-crystallin components only. The spectral features of one selected gamma-crystallin component (characterized by an isoelectric point of 7.68) have been examined. Results seem to suggest the presence of oxidative products of tryptophan. Implications of these findings for the expression of human and bovine genes are also considered. PMID- 2923917 TI - The influence of calcium ions on fibrinogen conformation. AB - The conformation of fibrinogen has been examined using the techniques of dye photosensitized surface labelling and cross-linking. The results obtained suggest that fibrinogen is a flexible molecule and its conformation is influenced by the concentration of calcium ions. These effects are mediated through binding to the low-affinity calcium binding sites of fibrinogen. In particular the C-terminal regions of the [A]alpha chain are more exposed at higher calcium concentrations creating a molecule which is more liable to form inter-molecular interactions. PMID- 2923918 TI - Protein folding and aggregation studied by isoelectric focusing across a urea gradient and isoelectric focusing in two dimensions. AB - Isoelectric focusing across a concentration gradient of urea was used to study the folding-unfolding and association-dissociation processes of proteins. Myoglobulin, albumin, RNase, papain, beta L- and alpha-crystallin were analyzed with this technique, and examples are given of visualized dissociation steps and of equilibrium-unfolding intermediates. Furthermore, a two-dimensional isoelectric focusing technique is presented that is useful to deduce whether a transition of a protein aggregate observed upon urea-gradient isoelectric focusing must be attributed to a change in the protein's tertiary or quaternary structure. PMID- 2923919 TI - Folding-unfolding and aggregation-dissociation of bovine alpha-crystallin subunits; evidence for unfolding intermediates of the alpha A subunits. AB - The aggregation and dissociation behavior of bovine alpha-crystallin as well as the folding and unfolding of its subunits were investigated by equilibrium studies using tryptophan fluorescence measurements and two isoelectric focusing techniques, viz. isoelectric focusing across a urea gradient and isoelectric focusing in two dimensions with different concentrations of urea. It was found that the alpha B chains lose their ability to aggregate and start unfolding at a lower concentration of urea than the alpha A chains. Equilibrium intermediates were found upon unfolding or refolding of alpha A subunits, which can be explained by a two-domain organization of these molecules. PMID- 2923920 TI - Activation of glutamate dehydrogenase by L-leucine. AB - The activation of glutamate dehydrogenase (L-glutamate: NAD(P)+ oxidoreductase (deaminating), EC 1.4.1.3) by L-leucine has been studied. Apparently homogeneous preparations from ox liver and brain were found to respond similarly. Commercially obtained preparations of the enzyme, which had suffered limited proteolysis during the purification procedure, were shown to behave similarly to preparations which had not suffered such proteolysis when the effects of L leucine on the oxidative deamination reaction were studied using either NAD+ or NADP+ as the coenzyme. There was also no significant difference in the responses when the reductive reaction was determined with NADPH or with 40 microM NADH. At higher concentrations of NADH (160 microM) the unproteolysed preparations were activated by L-leucine to a considerably greater extent than those which had suffered limited proteolysis. These results accord with the greater sensitivity of the former preparations to inhibition by high concentrations of NADH and the relief of such inhibition by L-leucine. This amino acid was also found to relieve the inhibition of the enzyme by GTP, resulting in an apparent increase in the activation observed in the presence of this nucleotide. In contrast, under the conditions used in this work, the apparent degree of activation by L-leucine was found to be decreased in the presence of the activators ATP or ADP. The presence of high concentrations of NADH (200 microM) potentiated the high substrate inhibition by 2-oxoglutarate, and L-leucine significantly reduced this effect. The effects of L-leucine on the activity of glutamate dehydrogenase thus appear to be composed of a direct effect on the activity of the enzyme together with a relief of high substrate inhibition. The effects of GTP and 2-oxoglutarate in potentiating inhibition by NADH can account for their effects in enhancing the apparent activation by L-leucine. The marked differences in the responses of proteolysed and unproteolysed preparations of the enzyme result from the effects of proteolysis in decreasing the sensitivity to high concentrations of NADH. PMID- 2923921 TI - An interpretation of 1/f fluctuations in neuronal spike trains during dream sleep. AB - The mesencephalic reticular formation (MRF) neurons are regarded as contributing to the activation of the cerebral cortex. We have investigated the statistical characteristics of the single neuronal activity in the MRF of cat during two activated states: paradoxical sleep (PS) and state in which the animal is watching birds (BW). 1/f-like spectra are observed for both PS and BW states, being more pronounced for PS state. For the interpretation of these findings, we have applied the clustering Poisson process, which not only gives rise to a 1/f spectrum but also suggests a generation mechanism. The MRF neuronal activities in PS and BW are closely fitted by the clustering Poisson process, both in terms of power spectral density and counting statistics. These results strongly suggest that the activities of MRF neurons in PS and BW can be interpreted as the superpositions of randomly occurring clusters which consist of various number of impulses. PMID- 2923922 TI - A nonlinear model for collicular spatial interactions underlying the metrical properties of electrically elicited saccades. AB - An earlier model for the collicular role in the generation of saccades (Van Gisbergen et al. 1987), based on ensemble coding and linear vector addition of movement contributions from independent movement cells, yields normometric saccades in all directions over a considerable range of amplitudes. The model, however, cannot account for two nonlinear phenomena which are known from collicular electrical stimulation experiments: 1) saccade amplitude has a roughly sigmoid dependence upon current strength and 2) two electrical stimuli applied simultaneously at different sites yield a response that resembles a weighted average of the individual responses. In the present paper we propose an intracollicular mechanism which, based on lateral spatial interactions in the deeper layers of the colliculus, results in nearby excitation and remote inhibition when current is applied. Both nonlinear phenomena can thus be explained. The possibility of excitatory and inhibitory collicular interactions is supported by recent evidence in the literature. The nonlinearity in the model, essential to explain the electrical stimulation findings, resides in the input output characteristic of the deeper layer movement cells. The results, obtained by quantitative simulations with the model, are discussed together with possible alternative explanations. PMID- 2923923 TI - A model of otolith stimulation. AB - A new model of otolithic stimulation by linear acceleration is presented and compared to previous models, based upon anatomical evidence and on the ability of normal subjects to sense the direction of a linear acceleration vector acting in the coronal plane (roll-tilt perception). There are two basic methods of generating roll-tilt stimuli: 1) tilt-chairs either inside or outside a centrifuge and 2) fixed-chair centrifuges. The present model is based on consideration of the probable otoconial displacement produced by these two different methods of stimulation and the model incorporates a major role for the elastic restoring force of the otolith membrane. When this force is taken into account, and most previous models have ignored it, the model predicts that different patterns of otoconial displacement will be produced in tilt-chair and in fixed-chair centrifuge experiments. The different roll-tilt perception produced by these two methods may be caused by the different otoconial displacement patterns. It is suggested that the elastic restoring force of the otoconial membrane may contribute to space motion sickness. PMID- 2923924 TI - Model of neural visual system with self-organizing cells. AB - This paper describes a model of a neural visual system of a higher animal, in which the capability of pattern recognition develops adaptively. To produce the adaptability, we adopted "self-organizing cells," and with them modeled feature detecting cells which were discovered by Hubel and Wiesel and whose plasticity was found by Blakemore and Cooper. Combining the "self-organizing cells" and the learning principle of a Perceptron-type system, we constructed a model of the whole visual system. The model is also equipped with an eye movement control mechanism for gazing, which reduces the number of "self-organizing cells" required for pattern recognition, thus contributing to their quick self organization. Computer simulation and an experiment using a hardware simulator showed that "self-organizing cells" quickly become sensitive to the features often seen and that the resulted system can classify patterns with a rather small number of feature-detecting cells. PMID- 2923925 TI - Detection of feedback in the central nervous system using system identification techniques. AB - An analysis method to detect the presence of feedback between biological signals, particularly those associated with the central nervous system, is presented. The technique is based on recent results in the system identification literature involving the concept of a feedback free process. It may be applied to volume conducted signals such as EEG and EMG, as well as to neuronal spike trains through the use of a data transformation procedure. The utility of the technique is then demonstrated in a study of the relationship between Parkinsonian tremor and certain tremor cells found in the thalamus of Parkinsonian patients, using data collected during thalamotomies. The results obtained suggest that feedback mechanisms may be an important factor contributing to Parkinsonian tremor. PMID- 2923926 TI - On the visual orientation of random dot Moire patterns. AB - We studied the orientation perception of dot patterns with Moire effect. The Moire effect was achieved by rotating the original patterns over small angles. When the angle was increased the effect disappeared while the characteristics of orientation estimation remained unchanged. For relatively small angles the subjects performance can be described by a model based on the concept of least squared distance axis. For large angles of rotation this model has began to be insufficient and a more refined model is proposed here. PMID- 2923927 TI - Jerk-cost modulations during the practice of rapid arm movements. AB - We examined how hand-trajectory smoothness changed during the practice of a motor task where smoothness was quantified by jerk-cost. Four human subjects each moved his nondominant arm between an upper target and a lower target, while circumnavigating a barrier that extended outward from the vertical plane of the targets. The two targets and the barrier placed boundary constraints on hand trajectories, but the motion was not restrained in any other way. Arm movements were recorded on high-speed cine film, and linear and angular kinematical data were obtained for all arm segments. In each of 100 practice trials, subjects attempted to minimize movement time. After the practice trials, subjects repeated the same motor task but at movement times corresponding to the slowest, mid-range and fastest motion that had occurred during practice. Thus, jerk-cost could be compared for movements of different speeds during practice and after practice. Because the movement task contained several changes in hand-path direction, the changes in the vector characteristics of the hand accelerations were expected to be important for explaining the modulations in jerk-cost with practice. Total jerk-cost, therefore, was calculated as well as the separate magnitudinal and directional jerk-cost components. During practice, total movement time decreased, hand paths became more parabolic in shape, and significant changes occurred in hand acceleration magnitude, direction, and timing. Total jerk-cost and the magnitudinal and directional jerk-cost components were significantly less when slowest hand movements were compared after practice versus during practice. The decrease in jerk-cost indicated an increased smoothness of the practiced movements. PMID- 2923928 TI - Differential spatial displacement discrimination with interfering stimuli. AB - Differential spatial displacement discrimination thresholds were determined for a configuration of three blobs with Gaussian spatial and temporal contrast envelopes. This task is similar to the well known three-dot alignment hyperacuity task. Thresholds determined in the presence of interfering stimuli were identical to thresholds determined without these flanking stimuli. The thresholds scale linearly with stimulus size over at least two decades. We conclude that (i) the mechanisms that compute differential spatial displacement for the three-blob alignment task are not disturbed by the presence of neighbouring stimuli, even when these enter the region over which the computations are performed and (ii) at all levels of resolution similar mechanisms are used to compute differential spatial displacement. PMID- 2923929 TI - Lactate-induced anxiety. PMID- 2923930 TI - SOD-1 activity and platelet membrane fluidity in Alzheimer's disease. AB - An early-onset, familial form of Alzheimer's disease (AD) has been reported to be linked to a locus on the long arm of chromosome 21 (21q21). Furthermore, duplications in the vicinity of this locus involving the beta-amyloid gene and the proto-oncogene ets-2 have been reported in association with AD. The structural gene for Cu,Zn superoxide dismutase, SOD-1, is located between the beta-amyloid gene and ets-2. For this reason and because SOD-1 is a plausible candidate for a gene that might influence the fluidity of cellular membranes, we determined whether or not the subtype of AD with increased platelet membrane fluidity was associated with an increase in Cu,Zn superoxide dismutase activity. PMID- 2923931 TI - A preliminary study of the effects of intravenous m-chlorophenylpiperazine, a serotonin agonist, in elderly subjects. AB - m-Chlorophenylpiperazine (m-CPP), a serotonin receptor agonist, is currently being investigated as a probe of serotonergic responsivity in various neuropsychiatric disorders. The safety of m-CPP in elderly populations and its potential usefulness in exploring possible serotonergic dysfunction in Alzheimer's disease and normal aging were assessed by examining the behavioral, neuroendocrine, and physiological effects of this agent in 15 elderly subjects (mean age 69 +/- 2 years): 9 Alzheimer patients and 6 healthy normal volunteers. Intravenous m-CPP (0.08 mg/kg) was well tolerated in all subjects and produced no serious adverse effects. The behavioral effects were modest; in particular, minimal anxiety was observed, a finding that contrasted to results from an earlier study reporting that intravenous m-CPP at a slightly higher dose induced marked anxiety and panic attacks in younger subjects. m-CPP produced significant increases in plasma cortisol and prolactin, and significant changes in blood pressure and temperature in these elderly subjects. The results of this preliminary study suggest that intravenous m-CPP is safe and well-tolerated in elderly subjects. Future studies at higher doses can now proceed to study more definitively the question of possible age- and disorder-related reductions in central nervous system (CNS) serotonergic responsivity. PMID- 2923932 TI - Prolactin response to fentanyl in depression. AB - Ten unmedicated female inpatients with major depression (DSM-III) and 10 healthy volunteer women were given an intravenous injection of 0.1 mg fentanyl at 9:00 AM and 9:00 PM on different days. The prolactin secretory response to this opioid agonist was investigated for 1 h with serial blood sampling. Repeated measures Analysis of Variance yielded a significant effect of fentanyl administration on prolactin secretion (p less than 0.0001), and there were elevated hormone responses in the evening (p less than 0.005). No group difference was seen between healthy volunteers and depressed patients, but four of the depressives showed the most blunted response, and three of these low responders committed suicide within 1 year. PMID- 2923933 TI - Correlations between abnormal auditory P300 topography and positive symptoms in schizophrenia: a preliminary report. AB - P300 component amplitude in the left temporal scalp region, shown in three previous studies to differentiate normals from schizophrenics, was found to be significantly correlated with the Thought Disorder Index (TDI) and the Scale for the Assessment of Positive Symptoms (SAPS). These correlations occurred primarily in the P300 waveform derived from the Goodin paradigm. These findings suggest a brain processing disturbance in positive symptom schizophrenia that may be reflected by electrophysiological abnormalities detectable in the temporal scalp region. PMID- 2923934 TI - Antiseptal brain antibody in IgG of schizophrenic patients. AB - On the hypothesis that schizophrenia is an immunological disorder in which antibody is produced against a unique antigen sequestered principally or exclusively in the septal region of the brain, we used crossed immunoelectrophoresis (CIE) to evaluate reactivity of a gamma G immunoglobulin (IgG) fraction from serum of schizophrenic patients and nonschizophrenic control subjects with homogenates of tissues of septal region, hippocampus, vermal cerebellum, frontal cortex, and liver of rhesus monkeys. When IgG fractions of unmedicated schizophrenic patients and schizophrenic patients who had received neuroleptic medication for less than 24 hr were tested against septal region homogenate, a precipitin arc was identified, indicating a positive result, with more than 95% of the fractions. In contrast, IgG fractions of schizophrenic patients who had received neuroleptic medication for more than 24 hr were rarely positive. When schizophrenic fractions that tested positive against septal region homogenate were tested against homogenates of the other tissues, they were negative. Fractions of all nonschizophrenic control subjects were negative against all homogenates. PMID- 2923935 TI - Plasma catecholamine metabolites and treatment response at neuroleptic steady state. AB - Using either haloperidol or perphenazine in a fixed-dose protocol, plasma free homovanillic acid (HVA) and methoxyhydroxyphenethylglycol (MHPG) were decreased in 37 nonorganic psychotic inpatients at neuroleptic steady state (7-9 days) in comparison with pretreatment values. The data indicate that the magnitude of the decline in HVA and MHPG was associated with treatment response and not with neuroleptic plasma levels. PMID- 2923936 TI - The plasma dexamethasone window: evidence supporting its usefulness to validate dexamethasone suppression test results. AB - Two doses of dexamethasone (DEX) (0.5 and 1.0 mg) were administered in a randomized crossover design to 31 patients with major depression, 9 healthy controls, and 14 nondepressed psychiatric patients. Using this modified Dexamethasone Suppression Test (DST), minimum DEX levels of 6 nmol/liter at 8:00 AM and 2.0 nmol/liter at 4:00 PM were required to achieve reliable suppression of cortisol in healthy controls and nondepressed psychiatric patients. Failure to achieve these minimum plasma DEX levels was associated with similar rates of nonsuppression in both depressed and nondepressed patients, thereby reducing the specificity of the DST. Conversely, high DEX levels greater than 13 nmol/liter at 8:00 AM or 4.0 nmol/liter at 4:00 PM were associated with abnormal "suppressibility" in depressed patients, thereby reducing the sensitivity of the test. Controlling for plasma DEX concentrations by selecting a test result that fell within a plasma DEX window at 8:00 AM and 4:00 PM increased the sensitivity and specificity of the DST. Significant differences in plasma DEX between suppressors and nonsuppressors were no longer evident when comparing patients with adequate DEX levels, thus ensuring that cortisol escape reflected HPA axis changes associated with depression and not peripheral mechanisms responsible for the availability of DEX. These results suggest that the clinical utility of the DST would be significantly enhanced by extending the standard 1.0-mg DST and retesting those patients with levels outside the DEX window with a higher or lower dose. The data also indicate that the measurement of plasma DEX is essential to validly interpret DST status and highlight the need to standardize DEX assays to compare DST results between research centers. PMID- 2923937 TI - Pancreatic encephalopathy. PMID- 2923938 TI - Abnormal visual evoked response in melancholia. PMID- 2923939 TI - Normal P300 in acute schizophrenics during a continuous performance test. PMID- 2923940 TI - Plasma norepinephrine response to exercise in bulimia, anorexia nervosa, and controls. PMID- 2923941 TI - Lack of association between HLA antigens and bulimia. PMID- 2923942 TI - Mianserin withdrawal and the pupil response of depressed and recovered patients: a preliminary report. PMID- 2923943 TI - Sensitivity of regional brain dopamine systems to haloperidol. PMID- 2923944 TI - Effects of oxaprotiline on the response to peer separation in rhesus monkeys. PMID- 2923945 TI - Plasma luteinizing hormone levels in normal and prenatally stressed male and female rat fetuses and their mothers. AB - Concentrations of luteinizing hormone (LH) were measured in plasma of fetal and neonatal rats obtained from control mothers and from mothers exposed to stress from Days 14 to 21 of gestation. The regimen of stress used is known to be associated with an abnormal ontogenetic pattern of testosterone secretion from the fetal testes. The overall ontogenetic pattern of immunoreactive LH levels in plasma was similar in male and female rats, and was unaffected by stress. In all groups, LH was low from Days 16 to 20 of gestation, and then rose progressively through birth, i.e. Day 23. However, stressing the mother significantly decreased the already low levels of LH between Days 16 and 20, as indicated by a larger percentage of samples from stressed fetuses of both sexes with LH levels below the limit of sensitivity of the assay. Sex differences in both the control and stressed group became evident only after Day 20 of gestation, with plasma concentrations of females exceeding those of males from Day 21 to 23 post conception. PMID- 2923946 TI - Influences of the paraventricular and suprachiasmatic nuclei and olfactory bulbs on melatonin responses in the golden hamster. AB - Removal of the pineal, or denervation of this gland by superior cervical ganglionectomy, blocks testicular regression in golden hamsters exposed to short photoperiods. Aspiration of the olfactory bulbs or lesions of the suprachiasmatic or paraventricular nuclei of the hypothalamus (SCNx or PVNx) have similar effects. We have examined the effects of these operations on pineal melatonin content and gonadal responses to various patterns of exogenous melatonin in order to examine the roles played by the olfactory bulbs, the SCN, and the PVN in hamster photoperiodism. SCNx and PVNx significantly reduced pineal melatonin content throughout the dark phase, while bulbectomy did not significantly affect melatonin concentrations at the time of the nocturnal peak. Bulbectomy significantly delayed the nightly onset of locomotor activity in hamsters exposed to 14L:10D, but not that of animals housed in 10L:14D. Although bulbectomy reduced the gonadal response to one or three daily injections of melatonin, these individuals exhibited significant testicular regression in response to melatonin as long as injections fell in the evening. In contrast, destruction of the PVN rendered hamsters unresponsive to one daily melatonin injection, but equally responsive to three injections, regardless of the time of day at which these injections were given. Whereas exposure of bulbectomized hamsters to 30 weeks of short days made them refractory to subsequent melatonin challenge, PVNx hamsters remained sensitive to appropriately timed melatonin treatments regardless of their photoperiodic history. Many, but not all hamsters that experienced complete SCN lesions remained sensitive to three daily melatonin injections.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2923947 TI - Rapid Leydig cell proliferation and luteinizing hormone receptor replenishment in the neonatal rat testis after a single injection of human chorionic gonadotropin. AB - Two-day-old rats were stimulated with a single dose of human chorionic gonadotropin (hCG). Changes in the Leydig cell number, mitotic activity, cell size, and number of luteinizing hormone (LH) receptors were studied. The Leydig cell number of the hCG-treated animals was 1.8 times that of the control on Day 1 and remained elevated for the rest of the 5-day experiment (p less than 0.0001). On Day 1 the number of Leydig cell mitoses in the hCG group was greater (p less than 0.05) than in the controls. The Leydig cell size increased transiently to two times that of the control (p less than 0.01) within the first day after the treatment and returned to control size by Day 5. The number of LH receptors per testis decreased 81% in 1 day (p less than 0.01), but returned to control level by Day 3. Since Leydig cell numbers were constant after Day 1, the rapid receptor recovery was obviously due to restoration of the binding sites rather than increased cell number. The present results demonstrate a rapid proliferative response and rapid LH receptor replenishment in the fetal-neonatal Leydig cells after gonadotropic stimulation. These responses of fetal-type Leydig cells are in clear contrast to those observed in adult testes after a similar stimulation. PMID- 2923948 TI - Biopsy of preimplantation mouse embryos: development of micromanipulated embryos and proliferation of single blastomeres in vitro. AB - We have developed a technique to sample the preimplantation embryo, which may, in the future, be applied to prenatal diagnosis of genetic disease. Using micromanipulation, we aspirated a single blastomere from 4-cell mouse embryos. This procedure had no effect on in vitro development; 98% of control and 94% of biopsied embryos reached the blastocyst stage after 48 h in culture. Furthermore, after transfer to pseudopregnant recipient mice, the rate of fetal development of biopsied embryos was not significantly different from control embryos, although implantation rate was significantly reduced (mean +/- SD: biopsied 53.1 +/- 4.0, control 81.8 +/- 8.4, p less than 0.001). For the first time we have produced monolayer cell cultures derived from single preimplantation blastomeres. Individual biopsied blastomeres were cultured in vitro on different extracellular matrix components. Significantly greater cell proliferation was obtained in wells coated with fibronectin (FN), laminin (LN), and a complex of laminin and nidogen (LNC) than in a less specific matrix of swine skin gelatin (SSG). Mean (+/- SE) cell nuclei number per well after 6 days in culture was 6.4 +/- 2.1, 11.9 +/- 1.5, 19.8 +/- 2.9, and 20.9 +/- 2.6 in wells coated with SSG, LN, FN, and LNC respectively. PMID- 2923949 TI - Differential activity and synthesis of lactate dehydrogenase isozymes A (muscle), B (heart), and C (testis) in mouse spermatogenic cells. AB - Spermatogenic cells isolated from adult and prepubertal mice by unit gravity sedimentation were used to examine enzyme activities and synthesis of the lactate dehydrogenase (LDH) isozymes during spermatogenesis. The synthesis and activity of LDH-C4, the germ cell-specific isozyme, was detected earliest in isolated preleptotene and leptotene/zygotene spermatocytes prior to the mid-pachytene stage of meiosis reported previously. The LDH-C4 isozyme was prominent in pachytene spermatocytes, round spermatids, and condensing spermatids, whereas spermatozoa contained only the LDH-C4 isozyme. In addition, somatic-type LDH isozymes consisting primarily of LDH-B subunits were present in germ cells throughout spermatogenesis. This is in contrast to a previous report that the LDH B subunit was not synthesized in germ cells. Sertoli cells were further shown to exhibit comparable amounts of five tetrameric LDH isozymes formed by combination of muscle-type LDH-A and heart-type LDH-B subunits. PMID- 2923950 TI - Rescue of atretic follicles in vitro and in vivo. AB - The purpose of this work was to determine if atretic follicles could be rescued and could return to the ovulatory pathway of development. Rats were given continuous infusions of 3H-thymidine (3H-thymidine (3H-TdR) resulting in uniform labeling of healthy antral follicles versus patchy labeling of atretic antral follicles. The infusion was then stopped and rats were subjected to experimental treatments known to stimulate follicular recruitment. Immature rats were given injections of pregnant mare's serum gonadotropin (PMSG) to provoke super ovulation. Adult rats were hemicastrated to provoke compensatory follicular development in the remaining ovary. In addition, granulosa cells from individual follicles of adult rats were cultured in vitro. The differential labeling patterns, observed at the end of the treatment period, were used to determine, a posteriori, the condition of follicles as they had been at the start of the treatment period. Sparsely labeled cell cultures were found, indicating that some cells from atretic follicles were able to become established in tissue culture. However, there was no evidence that atretic follicles had revived in vivo. All follicles recruited for ovulation by PMSG or hemicastration were heavily and uniformly labeled. All poorly labeled follicles were clearly continuing their process of degeneration. These observations suggest that, despite continued viability of some granulosa cells in atretic follicles, once a follicle begins to degenerate in vivo, it will probably not return to the ovulatory pathway. PMID- 2923951 TI - Morphometric quantification of mitochondria in the two steroidogenic ovine luteal cell types. AB - Progesterone secretion is regulated by different mechanisms in large and small steroidogenic ovine luteal cells. Large cells secrete approximately 7-fold more progesterone in an unstimulated state than small cells. Since cholesterol side chain cleavage, which is catalyzed by an inner mitochondrial membrane enzyme complex, is a major rate-limiting step in progesterone synthesis, mitochondrial components were quantified in the two steroidogenic cell types throughout the estrous cycle. Corpora lutea collected on Days 4 (n = 4), 8 (n = 4), 12 (n = 5), and 16 (n = 6) of the estrous cycle were prepared for electron microscopy. Volume densities of cell types within corpora lutea and mitochondrial densities within cell types were estimated by point-counting; nuclear and cytoplasmic volume densities were estimated by planimetric analysis. A total of 570 micrographs (magnification 5300 X) were analyzed. Large cell volume density was unchanged during the cycle (35 +/- 1%) while small cell volume density increased (p less than 0.05) from 13 +/- 1% on Day 4 to 20 +/- 3% on Day 12. Large cell mitochondrial volume density increased (p less than 0.05) from 13 +/- 1% on Day 4 to 23 +/- 1% on Day 16 accompanied by an increase in cytoplasmic volume density such that nuclear to cytoplasmic ratio increased (p less than 0.05) from 1:14 to 1:34 between Days 4 and 16. Small cell mitochondrial volume density increased from 11 +/- 1% on Day 4 to 14 +/- 1% (p less than 0.05) for the rest of the cycle while the nuclear to cytoplasmic ratio remained at 1:14.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2923952 TI - The effect of estrogen on androstenedione production by rat placental cells in vitro. AB - We have recently provided evidence from studies conducted in vivo that the ovary, particularly by means of estrogen, regulates placental androstenedione (delta 4A) production during the second half of rat pregnancy. In the present study, an incubation system of dispersed rat placental cells was established to determine if estrogen acts directly on the placenta to regulate delta 4A production. Placentas were obtained on Days 14-15 of rat gestation and dispersed in Hanks' Balanced Salt Solution containing 0.1% collagenase, 0.1% hyaluronidase, 0.01% DNase, and 1% fetal calf serum. Placental cells were incubated in Medium 199 for 16 h at 37 degrees C. A time-dependent increase (r = 0.96, p less than 0.05) in the release of delta 4A occurred over the 16-h incubation period. Mean +/- SE formation of the steroid intermediate progesterone (P4) and product delta 4A was 1.17 +/- 0.78 and 1.18 +/- 0.22 ng per 10(7) cells respectively. The addition of 1-10 microM diethylstilbestrol (DES) decreased (p less than 0.05-0.01) delta 4A production, and had no significant effect on P4 or pregnenolone (P5) formation. The percent decrease in delta 4A production was 14.2 +/- 12.9, 30.9 +/- 2.3, and 55.0 +/- 4.4 with 1, 5, and 10 microM DES, respectively. Treatment of placental cells with estradiol (E2) also resulted in a decrease (p less than 0.01) in delta 4A production with no effect on P4 formation. The percent inhibition of delta 4A production was 34.2 +/- 11.1 and 77.3 +/- 5.2 with the addition of 1 microM and 10 microM E2, respectively. E2 (10 microM) produced a concomitant threefold increase (p less than 0.01) in P5 formation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2923953 TI - Reproductive refractoriness in the Welsh Mountain ewe induced by a short photoperiod can be overridden by exposure to a shorter photoperiod. AB - The objectives were to determine if relative lengths of photoperiods that induce reproductive cycles in ewes affect the length of the subsequent breeding season, if duration of the refractoriness that terminates breeding is affected by photoperiod length, and if the resulting refractoriness to an inductive photoperiod is absolute. Groups of Welsh Mountain ewes were exposed to either 12L:12D (n = 12) or 8L:16D (n = 6) photoperiods beginning at the summer solstice when daylengths reach a maximum of 17.5 h at Bristol, England. A control group (n = 10) was exposed to natural daylengths. Ovarian cycles in the controls, as judged by monitored plasma progesterone levels, commenced in early October, about 1 mo later (p less than 0.001 in both cases) than in sheep exposed to 12L:12D or 8L:16D. The advancement in cycle onset was similar under 12L:12D and 8L:16D (69 +/- 2 and 77 +/- 4 days after the summer solstice compared with 102 +/- 2 days in the controls). Duration of the breeding season (100 +/- 4 days) in ewes exposed to 12L:12D was significantly shorter (p less than 0.001 in both cases) than in ewes exposed to natural daylengths or 8L:16D (153 +/- 3 and 133 +/- 5 days, respectively). Approximately 70 days after the ending of ovulatory cycles in the 12L:12D group, half of the animals (n = 6) were transferred to 8L:16D. This treatment greatly (p less than 0.001) reduced the duration of anestrus and cycles began again 62 +/- 4 days after transfer to 8L:16D, or about 90 days earlier than in ewes (n = 6) remaining in 12L:12D.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2923954 TI - Induction of persistent diestrus followed by persistent estrus is indicative of delayed maturation of tonic gonadotropin-releasing systems in rats. AB - The relationship between the amount and duration of administration of estradiol benzoate (EB) to newborn female rats and the induction of sterility was examined in 407 animals. Vaginal smear patterns were classified into 3 types according to the incidence of vaginal proestrus and estrus over a 10-day period: persistent estrous (PE), persistent diestrus (PD), and intermediate (INT), so that the changes in vaginal smear patterns could be analyzed quantitatively. Incidence of the PE pattern was most frequent in the rats that received a single injection of 10 micrograms EB on the day of birth (Day 1). Almost all of the animals receiving 10 daily injections of 10 micrograms EB from Day 1 showed persistent diestrus until at least 100 days of age. In the rats that were given 5 daily injections of 10 micrograms EB Day 1 through Day 5, or a single injection of 100 micrograms EB on Day 3, the incidence of the PD pattern was high at 41-60 days of age, but later the PD-type was replaced by the PE pattern of vaginal smears. In the rats that were treated with 5 daily injections of 10 micrograms EB from Day 1 through Day 5 and were ovariectomized on Day 22, a slight but significant increase in the level of luteinizing hormone in plasma was noted after administration of EB and progesterone on Day 100 but not on Day 50. These results indicated that neonatal injections of EB induce sterility, but the effect is dependent on the amount of EB injected and length of time over which the injections are given.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2923955 TI - Pharmacokinetics of acetaminophen after intramuscular administration. PMID- 2923956 TI - Stability study of diltiazem and two of its metabolites using a high performance liquid chromatographic method. PMID- 2923957 TI - Effect of cimetidine on quinidine bioavailability. AB - Elevations in quinidine steady-state serum concentrations have been reported in patients who received cimetidine concurrently. Studies in normal volunteers have shown that areas under the serum concentration-time curve of orally administered quinidine are higher when quinidine is given during chronic cimetidine therapy as compared to under control conditions. The mechanism for this interaction is generally ascribed to decreased hepatic clearance as a consequence of enzyme inhibition. In this study, we show that cimetidine also decreases the bioavailable fraction of quinidine. PMID- 2923958 TI - Estimation problem due to multiple solutions in pharmacokinetic curve fitting to two-compartment model and its avoidance. AB - A size of error in observed data for fitting curves and an estimation problem due to multiple solutions in a two-compartment model were studied by using two different non-linear least-squares regression programs, SALS and NONLIN. It was found that bolus intravenous data have generally 5-10 per cent errors and oral data contain 10-25 per cent errors against the fitted data with respect to total 151 data sets of 11 different drugs. Parameters of five drugs reported in references were used to obtain simulated concentrations at the sampling times, and five different data sets containing 25 per cent normally distributed random errors as a coefficient of variation were generated using each data set of these simulated concentration. In the two-compartment model with tri-exponential equations, unreasonable estimates were occasionally observed, resulting in reversed relative values to the theoretical ones of L/M, L/N, M/N or Ka/alpha, which are analogous to the well-known flip-flop phenomenon in the one-compartment model, when number of parameters to be estimated is not less than five or errors of data exceed about 10 per cent. In an attempt to avoid such unreasonable values, initial estimates for curve fitting was successfully obtained by using a microcomputer program SIMPLEX based on a simplex method. On the basis of these results, some problems in curve fitting of plasma drug concentration data are discussed. PMID- 2923959 TI - Nonlinear least-squares regression analysis by a simplex method using differential equations containing Michaelis-Menten type rate constants. AB - Computer curve fittings were carried out to observed data as well as theoretically generated plasma concentrations of several drugs, using differential equations which contained nonlinear Michaelis-Menten type rate constants to discuss problems of initial parameter estimation in pharmacokinetic analysis. Calculation based on two different algorithms, each carried out by using SIMP (simplex method) and NONLIN (modified Gauss-Newton method) produced similar results. However, occasional divergence or unreasonable solutions occurred in a later case, when assumed values of Km and Vmax were used as initial parameters. A combined use of SIMP and NONLIN in which calculated values by SIMP were used as initial values for NONLIN, was shown to be effective to analyse plasma concentration data of indocyanine green bearing difficulty in estimating initial values. It is suggested that the successive method is useful for the curve fitting of plasma concentration with nonlinear pharmacokinetic rate processes. PMID- 2923960 TI - Toward a quantitative approach for the prediction of the fraction of dose absorbed using the absorption potential concept. AB - An equation based on the absorption potential concept was developed. This enabled us to establish an approach for the quantitative prediction of the fraction of dose absorbed. Classification of drugs into three broad categories, according to their absorption potential values in relation to the fraction of dose absorbed, was attempted. The new approach was tested using literature data with very good results. PMID- 2923961 TI - Dissociation of authentic and artifactual effect of circulating heparin on drug protein binding. AB - The purpose of this study was to dissociate the authentic and artifactual effect of in vivo heparin on drug protein binding using protamine as an inhibitor of ex vivo lipolysis. A mixture of ethylenediamine tetra-acetic acid (EDTA, 5 mg ml-1) and protamine in the concentration range of 0 to 7.5 mg ml-1 was added to blood samples from 23 cardiac catheterized patients before (control) and 10 min after 3000 IU of intravenous heparin. In control samples, protamine does not interfere with the protein binding of lidocaine (L), quinidine (Q) or propranolol (P) when plasma pH is readjusted to 7.4. In the absence of protamine, heparin induced a significant increase in the free fraction by 40, 130, and 30 per cent for L, Q, and P, respectively (p less than 0.001), while free fatty acid (FFA) levels increased 2 to 6 fold. When protamine was present, the heparin-induced elevation in free fraction was significantly lower for L (16 per cent) and Q (77 per cent) but not for P; FFA levels were decreased at all protamine concentrations. Residual increases in free fraction and FFA levels compared to control values may represent the true in vivo effect of heparin at the peak activity of lipoprotein lipases. For L and Q, variations in free fraction were strongly associated with variations in FFA, but for P, no significant correlation was observed (r = 0.492). These results indicate that variations in free fraction of L and Q caused by heparin are, to a large extent, artifactual but may be prevented by use of protamine in collection tubes (5 to 7.5 mg ml-1). For P, the increase in free fraction was not mediated by variations of FFA indicating that another mechanism must be involved. PMID- 2923962 TI - Bioavailability of propranolol hydrochloride tablet formulations: application of multiple dose crossover studies. AB - Two multiple dose crossover pharmacokinetic studies were carried out to determine the steady-state bioavailability of newly formulated generic propranolol HCl tablets relative to Inderal tablets. In Study I, 24 healthy volunteers were dosed with 4 x 10 mg test tablets, 1 x 40 mg test tablet, 4 x 10 mg Inderal tablets, and 40 mg of propranolol HCl in solution. In Study II, 24 healthy volunteers were dosed with 1 x 80 mg test tablet, 1 x 80 mg Inderal tablet, and 80 mg of propranolol HCl in solution. Both studies were of randomized design with each formulation administered every 8 h for 15 doses. Serial plasma samples were obtained for 8 h after morning doses on Days 4 and 5 of each treatment period and assayed for propranolol using a validated HPLC method. Mean plasma concentration time data for test tablets and reference tablets were superimposable in both studies. Pharmacokinetic parameters from Days 4 and 5 were combined for statistical analysis since subjects were determined to have reached steady-state. Mean AUC, Cmax, tmax, and Cmin values were not statistically different between test tablets and Inderal tablets in either study. Based on these findings, the test tablets demonstrated the same rate and extent of propranolol absorption as did corresponding Inderal tablets. Therefore, the test tablets and Inderal tablets were determined to be bioequivalent. PMID- 2923963 TI - Effects of equimolar doses of cimetidine and ranitidine on theophylline elimination. AB - The disposition of theophylline was studied on four occasions in eight healthy adult males. The control mean theophylline half-life and clearance were 7.32 h and 0.86 ml min-1 kg-1, respectively. After 5 days pretreatment with placebo the corresponding values of 7.01 and 0.88 were not significantly different, as were those of 7.43 and 0.85 after 5 days pretreatment with ranitidine (1.2 g daily). Five days pretreatment with cimetidine (1.0 g daily) resulted in a significant 44.4 per cent rise in the mean theophylline half-life and a 36.1 per cent fall in clearance. The fall in clearance correlated positively (r = 0.9407) with the initial value. The volume of distribution did not change significantly throughout the study period. The fact that, at as large a dose as 1.2 g daily, ranitidine did not impair theophylline metabolism suggests that similar results reported earlier with therapeutic doses of 300 mg daily cannot be ascribed to the lower dose of ranitidine employed. It is also suggested that the risk of theophylline toxicity consequent on cimetidine coadministration will be more likely in individuals with initial high theophylline clearance. PMID- 2923964 TI - Pharmacokinetics of theophylline before and after nephrectomy in dogs. AB - The role of the kidneys in the elimination of theophylline was directly assessed using nephrectomized dogs. Data was analyzed by two different pharmacokinetic approaches. Analysis indicated that a given dosage regimen produced significantly different serum concentrations before and after nephrectomy. Model independent pharmacokinetic analysis failed to show a significant difference in parameters. A model dependent approach, using a nonlinear regression analysis employing a linear two-compartment model, demonstrated that the differences observed could be accounted for by a change in the first order elimination kinetics. PMID- 2923965 TI - [The role of adrenergic mechanisms in regulating venular permeability during short-term and prolonged immobilization]. AB - In the experiments on rats by the method on contact luminescent biomicroscopy it was shown that the regulation venular permeability by catecholamines during short or long immobilization realized mainly by endothelial and mast cells beta adrenoceptors, but not by alpha-adrenoceptors. PMID- 2923966 TI - [Carnosine prevents the activation of free-radical lipid oxidation during stress]. AB - Carnosine (beta-alanyl-L-histidine) injected to intact albino rats (20 mg/kg body weight) induces depletion of lipid peroxidation (LPO) products in brain and blood serum, an increase of superoxide scavenging activity in brain and serum, decrease of cholesterol: phospholipid ratio and increase of easy oxidizable phospholipid portion in brain lipid extracts. After painful stress (footshock during 2 hours) LPO products are accumulated in brain and serum, cholesterol: phospholipid ratio increases and the portion of easy oxidizable phospholipids decreases. Carnosine given before stress prevents LPO activation. Effects of carnosine and stress are not additive: LPO inhibition induced by carnosine is much more in rats subjected to stress. PMID- 2923967 TI - [Determination of the leading factors in the pathogenesis of an alcoholic lesion of the heart]. AB - Male rats were given per os 25% ethanol solution twice a day at 9.00 and 21.00 for 5.5 consecutive days. Every single dose was 2 to 5 g/kg 2 and 12 hours after 8th gavage ethanol, acetaldehyde and acetone concentrations were measured in blood, 2-8 hours after the last (11th) gavage isolated hearts were perfused by Krebs-Henseleit solution. Applying of Spearman rank correlation method demonstrated negative correlation between mean acetaldehyde concentration and maximal systolic pressure, tension-time index of left ventricle and velocity of contraction and relaxation. Negative correlation has been shown between maximal ethanol concentration (MEC) and rate heart whereas positive correlation has been noticed between MEC and leakage of creatine phosphokinase. PMID- 2923968 TI - [Effect of a highly dispersed copper powder on superoxide dismutase and glutathione peroxidase activities in experimental myocardial infarct]. AB - Administration of highly dispersed copper powder in a dose 0.2 mg/kg three days before modelled coronary-occlusion myocardial infarction caused transitory increase in activity of antioxidant enzymes--superoxide dismutase and glutathione peroxidase in the necrotic zone of myocardium of rats, and also staunch increase in the activity of these enzymes in noninfarction region. PMID- 2923969 TI - [Pulmonary circulation in embolic pulmonary edema]. AB - The ultrasonic method was used in acute experiments on cats with open chest under artificial lung ventilation to obtain blood flow in low-lobar pulmonary artery and vein, the blood pressure in pulmonary artery, as well as the left atrial pressure in fat (olive oil) and mechanical (Lycopodium spores) pulmonary embolism. It is shown that pulmonary embolism produces the decrease in the blood flow in pulmonary artery and vein, the increase of the pressure in pulmonary artery and left atria, the increase of lung vessels resistance. The decrease is observed of systemic arterial pressure, bradycardia, and extrasystole. After 5-10 min the restoration of arterial pressure and heart rhythm occur and partial restoration of blood flow in pulmonary artery and vein. In many experiments the blood flow in vein outdoes that in the artery--it allows to suppose the increase of the blood flow in bronchial artery. After 60-90 min there occur sudden decrease of systemic arterial pressure, the decrease of the blood flow in pulmonary artery and vein. The pressure in pulmonary artery and resistance of pulmonary vessels remain high. Pulmonary edema developed in all animals. The death occurs in 60-100 min after the beginning of embolism. PMID- 2923970 TI - [Comparative characteristics of the changes in resistance in the vessels of the skeletal muscle and small intestine after the destruction of the structures in the ventral portions of the medulla oblongata]. AB - Different trends and manifestation of changes of blood pressure and regional vessel resistance depending on the localization and the method (chemical or electrical) of the lesion in ventral medulla oblongata, were analyzed. PMID- 2923971 TI - [Structural aspects of the functional activity of the cerebral cortex synapses in the early postresuscitation period]. AB - The numeral density of the revealed with the help of PTA-plane and twisted asymmetric and symmetric interneuronal contacts of the sensomotor brain cortex of rats after 6 minutes mechanical asphyxia has been studied. It was revealed that in 90 minutes and 6 hours the relative contacts of the concave synapses will be increased progressively. This reaction has the compensatory-adaptive character and ensures the restoration of the integrative activity of the brain during the early postresuscitation period. PMID- 2923972 TI - [Chloditan-induced changes in lipid peroxidation in the adrenals of dogs and guinea pigs]. AB - The effect of adrenocorticolytic drug chloditan (1-(o-chlorophenyl)-1-(p chlorophenyl)-2,2-dichloroethane;) on the content and the rate of lipid peroxidation in dog and guinea pig adrenals was studied. In adrenals of dogs and guinea the amount of malondialdehyde (MDA) was increased. In vitro spontaneous lipid peroxidation was delayed in adrenal homogenate of DDD-treated dogs. Spontaneous lipid peroxidation in adrenal homogenate was not decreased by feeding DDD in the guinea pig. DDD consumption did not affect on lipid peroxidation promoted by ascorbic acid and ferrous iron. The accumulation of MDA in dog and guinea pig adrenal homogenates was inhibited by NADPH. PMID- 2923973 TI - [The interrelationship of the processes of lipid peroxidation and lipid phospholipase hydrolysis in the synaptosomes]. AB - The influence of Fe2+, alpha-tocopherol, phospholipase A2 and mepacrine on the activity of lipid peroxidation (LPO) and phospholipid hydrolysis (PLH) was studied in synaptosomes. It was established that there is the tight direct interconnection between LPO and PLH in synaptosomes. It is assumed that activation of endogenous phospholipases in neurons is one of the causes of uncompensated LPO-activation during epileptogenesis. PMID- 2923974 TI - [Spectrophotometric method for determining the stability of lysosomes from animal tissues depending on the hydrogen ion concentration]. AB - Rapid spectrophotometric method of lysosome stability determination depending on hydrogen ion concentration is described. The time of analysis is decreased by 5-6 h in comparison with enzymic method. The process of lysosome degradation was linear at pH 6. The incubation mixture acidity dependence curve of lysosome lysis extend was complex. The lysosome lysis rate rapidly increased at pH much less than 6 less than pH. Lysosome incubation at 0-4 degrees C during 24 h decreased its sensitivity to incubation mixture acidity within the whole investigated pH range. Isolated lysosome acid resistance may be used as an index of its stability and lability in vivo and in vitro by various physicochemical factors. Percentage of initial absorbtion (A520) and initial lysosome lysis rate (delta A520/min) may be index of such effect. PMID- 2923975 TI - [Protective action of fat- and water-soluble antioxidants on the cytochrome P-450 system during lipid peroxidation in liver microsomes]. AB - The protective effects of alpha-tocopherol, carnosine and their mixture on monooxygenase system during lipid peroxidation in liver microsome membranes were studied. It was shown that for optimal protection effect of cytochrome P-450 system the mixture of water and liposoluble antioxidants is required. PMID- 2923976 TI - [Effect of an antiserum to brain gamma gamma-enolase (protein 14-3-2) on ethanol consumption by rats]. AB - The influence of intracisternal administration of antiserum to the neurospecific brain gamma gamma-enolase (aS-gamma gamma) on the consumption of 7.5% ethanol solution by rats was studied. Injection of aS-gamma gamma decreased the ethanol intake by the rats which had been drinking 15% solution of ethanol for 7 months as a single source of liquid. In vitro aS-gamma gamma caused 4-fold inhibition of the gamma gamma-enolase activity while it did not influence the alpha alpha enolase activity. Intracisternal administration of aS-gamma gamma shifted enolase isoenzyme spectra in the direction of the decrease of gamma gamma-enolase content. It is suggested that the effect of aS-gamma gamma on ethanol consumption is due to inhibition of the activity of gamma gamma-enolase which participates in energy metabolism in neurons. PMID- 2923977 TI - [Characteristics of memory in MRL/1 mice and the effect of thymic peptides]. AB - By means of methods of active and passive getting rid of electrical-pain irritation we showed that in mice MRL/1--the model of rheumatoid arthritis (RA)- as compared with CBA (control) the process of forming a developed habit engram (DHE) was slowed down and its keeping was impaired. Thymic peptides (thymalin- 0.2 mlg/mice intraperitoneally) suppressed the process of forming DHE irrespective of mice line and improved the process of its consolidation and keeping especially in mice MRL/1. Memory impairment in mice with genetical predisposition to the development of autoimmune process (MRL/1) is considered from view of the authors' developed hypothesis about thymus as an organ of antisystem of immune control of homeostasis and RA as an adaptation disease. PMID- 2923978 TI - [Effect of tuftsin on the leucyl aminopeptidase activity of the subcellular components in cerebral cortical formations]. AB - The administration of a tetrapeptide tuftsin in a dose of 300 mkg/kg body weight for 15, 75 minutes leads to the change in specific activity of leucyl-arylamidase in subcellular component and their membrane which has been isolated from the rabbit sensomotor cortex and visual cortex. Reaction of a tetrapeptide depends on time. It is strongly pronounced in sensomotor cortex and has an advantage in synaptosomes and their membrane. Possibility of tuftsin in protein exchange of cellular and subcellular component is discussed. PMID- 2923979 TI - [Differences in the receptor apparatus of resident and meat-peptone broth stimulated macrophage populations detectable under the action of salmozan]. AB - The degree of expression of lectin-like receptors in resident (RPM) and peptone elicited peritoneal macrophages (PE-PM) using salmozan as polysaccharide was investigated. Obtained results allow to suppose that salmozan screens lectin-like receptors in macrophages and SRBC. The salmozan screening of lectin-like receptors in macrophages and SRBC resulted in decrease of SRBC uptake level in RPM-subpopulation but did not alter it in PE-PM-subpopulation. The same effect was occurred with the intensified erythrocyte loading of this macrophage subpopulations. It is suggested that one of the functional differences of studied macrophage subpopulation consists in the largest expression of lectin-like receptors in RPM-subpopulation. PMID- 2923980 TI - [Latent autoantibodies to cardiolipin in the blood serum of healthy subjects]. AB - Pooled health blood donors' sera were fractionated by gel filtration and/or ion exchange chromatography on strong anion-exchanger. Measurement of anticardiolipin antibodies levels by ELISA method shows that gel filtration at pH 4.05 and 9.2 (complex-degradation conditions) leads to increase in summary levels while after elution at neutral pH such an effect did not appear. Light increasing of anticardiolipin levels was also noted after fractionation on QAE-Sephadex. Data obtained state that anticardiolipin autoantibodies amount in sera is greater than it can be detected by direct measurement in untreated serum samples. Existence of "hidden" anticardiolipin autoantibodies supposes the hypothesis about alternative way of humoral immunity regulation by blocking anti-self antigens activities with serum biopolymers. PMID- 2923981 TI - [Spontaneous and induced production of the tumor necrosis factor by the blood cells of newborn infants]. AB - The authors determined activity of tumor-necrotizing factor in the blood serum from the umbilical cord and venous blood in children aged 5-6 years and in supernatants from the culture of mononuclear blood cells after its cultivation in the course of 24 h with bacterial products. PMID- 2923982 TI - [An experimental analysis of the interrelation of the kinetics of spontaneous blood serum chemiluminescence and of the kinetics of the tumor process]. AB - On the material of 5 strains of transplanted rat tumours (sarcoma 45, carcinoma Guerin, carcinosarcoma Walker, lymphosarcoma Pliss, erythromyelosis Shvets) and also mice tumours induced by Moloney and Rauscher viruses and on the models of chemical carcinogenesis of rats: lung (intratracheal injection of 3,4 benz(a)pyrene), breast (DMBA) and liver DENA) was shown that tumorous processes of various origin are accompanied by either elevation or inhibition of blood serum spontaneous chemiluminescence (SChL). In all investigated cases the extreme points of SChL curve coincide with the moment of change of tumour growth kinetics. PMID- 2923983 TI - [Topographic distribution of proliferating hepatocytes in the hepatic lobe of intact rats during the course of 24 hours]. AB - The topographic distribution of DNA-synthesizing and divisible hepatocytes was studied in the hepatic lobe of intact rats during the 24-hours. For this purpose the indices of a number of DNA-synthesizing and divisible cells were determined both in a liver as a whole and for each lobe zone (periportal, middle and central one). The obtained results allowed to reveal the presence of the 24-hour rhythm of cell proliferation process in a liver as well as the regular topographic distribution of DNA-synthesizing and divisible hepatocytes during the period of their increased values in the rhythm. The process of activation of proliferation seems to start in the periportal zone, and then to hold the whole zone, with its dominance in the middle zone during the period of maximum values of the cell proliferation indices. One could suppose that this testifies to the equal proliferative potencies of hepatocytes irrespective of their localization as well as to the fact that the cells of all zones take part in the formation of acrophases of rhythms both of the DNA-synthesizing hepatocytes and divisible ones. However, the degree of their participation in this process is unequal and depends on the localization of cells in the hepatic lobe. PMID- 2923984 TI - [Effect of antioxidants on the indices of free-radical lipid oxidation in the testes of rats of different ages and on the reproductive capacity in chronic multiple antioxidant deficiency]. AB - The free-radical oxidation level of lipids in the rat's testicles of different age under the conditions of chronic and multiple antioxidant insufficiency has been studied, as well as the reproductive ability of male rats, kept at the nonantioxidant ration. The increase of free radical oxidation lipids in the testicles of animals with chronic multiple antioxidant insufficiency and the decrease of their reproductive ability has been observed. The antioxidant complex in such conditions had a defensive effect. The obtained results serve as the basis of the antioxidant use as the means of normalising the reproductive functions in males during period of low receipt and high expense of alimentary oxidants. PMID- 2923985 TI - [Effect of immobilization stress on the gonadotropic function of the hypophysis in male hamadryas baboons (Papio hamadryas)]. AB - The plasma levels of luteinizing hormone (LH) and testosterone were studied in intact and castrated male baboons exposed to 2- and 10-hour periods of immobilization. Presented data have shown that immobilization stress induced a marked decrease in LH concentration both in intact and castrated monkeys. Changes in LH concentration positively correlated with plasma levels of testosterone only during the experimental procedures. During three days after immobilization there was a sharp dissociation in the dynamics of testosterone levels remained low and LH returned to normal values. We can suggest that it is not absolute LH level that is responsible for the changes in testosterone secretion during the immobilization stress. PMID- 2923986 TI - [Effect of the thymus on the activity of immunoreactive peptides]. AB - Influence of the thymic gland on the biology activity of peptide mediators- cytomedins, has been studied in the content of different organs. The peptide which was obtained from the liver, spleen and muscle of sham-operated animals enhanced immune response on the sheep red cells, lengthened indexes of thromboelastography, and activated fibrinolysis after its administration to the thymectomized rats. The peptides from organs of thymectomized animals lost this ability. These findings confirm the hypothesis on the regulating function of the thymic gland in the synthesis and activity of cytomedins in the tissues. PMID- 2923987 TI - [Cytochemical study of the neurocytes of the rat locus coeruleus after guanethidine sympathectomy]. AB - The histone localization, template activity of chromatin and epinephrine fluorescence in L. Coeruleus (LC) neurons of normal a. guanethidine sympathectomized (GS) rats (15 mg/kg during 3, 8 or 14 days after birth) were studied. The absence of chromatin rearrangements connected with genome reprogramming under sympathectomy was documented by the fact that maximal doses of guanethidine gives no changes in ammoniacal silver staining pattern. However GS caused the decrease in nuclear and extranuclear template activity and in epinephrine fluorescence proportionally with GS. It is obvious that LC cells tend to form discrete classes according to their transcription levels. PMID- 2923988 TI - Cognitive mediation of responses to life stress. AB - Cognitive theories of psychopathology argue that thoughts play an active role between external events and subjective experience. These approaches suggest a "mediation hypothesis": adaptive thoughts should serve as buffers against life stresses. In the present study, we gathered data from 125 subjects regarding (1) the levels of stress they had experienced in the recent past; (2) their current feelings of anxiety and depression; and (3) the extent to which they endorsed illogical, unrealistic views of life. Contrary to the mediation hypothesis, no differential impact of environmental stress was found across levels of adaptive cognitions. Rather, adaptive cognitions emerged as a powerful independent variable, showing strong direct relations with measures of distress. It is argued that improved measures of environmental distress will be necessary to provide a more powerful test of the mediation hypothesis. PMID- 2923989 TI - Toxic waste: behavioral effects of an environmental stressor. AB - This study examines the stress-related behavioral effects that may be associated with living near an ambient stressor: a toxic-waste landfill. Results are based on a telephone survey of 426 persons living in three distance strata from the landfill (within 1 1/2 miles, 1 1/2 to 5 miles, and 5 to 10 miles). The instrument was adapted from the Hopkins Life Checklist (SCL-90) and from surveys used by researchers studying the effects of the Three Mile Island nuclear accident. No significant differences were found across area or amount of stimuli exposure on the dependent variables of bodily effects, anger-hostility, and demoralization. Scattered effects across age, sex, educational level, and home ownership (v rental) occurred; however, these could not be attributed solely to the landfill. PMID- 2923990 TI - Organizational characteristics, occupational stress, and mental health in nurses. AB - A model of occupational stress in hospital nurses was developed and tested. The model used measures of organizational climate, supervisor behavior, and work group relations as predictors of the quantity of role ambiguity perceived by nurses. Data were collected on 232 hospital nurses working in a rural community hospital affiliated with a medical school. Results confirmed the hypothesized structural model. Organizational climate, supervisor behavior, and work group relations directly influenced role perception. Increased role ambiguity led to decreased job satisfaction and increased perceived stress. The organizational environment directly influenced job stress. Occupational stress exerted a strong direct influence on the development of depressive symptoms in nurses. PMID- 2923991 TI - Relationship of hassles, uplifts, and life events to psychological well-being of freshman medical students. AB - Hassles, uplifts, and life events were related to psychological well-being with a representative sample of 55 (of 179) freshman medical students. Students were sent measures of hassles, uplifts, and affect-moods measures for 9 consecutive months and a measure of life stress at the beginning and middle of the school year. The hassles measure was found to be a better predictor of concurrent and subsequent negative mood than was the life stress measure, whereas life stress was found to be a better predictor of subsequent positive mood than hassles. On the whole, uplifts were unrelated to mood. The relationship between life stress and hassles was also investigated. The implications of the findings for future stress and health outcome research are discussed. PMID- 2923992 TI - Workload, stress, and strain among police officers. AB - Data relevant to stress and strain were analyzed separately for police officers with high and low workloads. Although these groups of officers were not found to differ in demographic characteristics or on overall levels of stress and strain, the sources of stress and strain were remarkably different. For the low workload officer, the sources of stress and strain appear to be difficulties in interpersonal relations with peers, community, and especially with supervisors. These difficulties appear to be mediated by effects on self-evaluation. The sources of stress and strain among high workload officers appear to be stress producing events in their lives in general, as well as in performing the job of patrol officer and in dealing with crime and related matters. The differences between high and low workload officers can be explained by social comparison theory, by identity theory, or by Selye's stress theory. PMID- 2923993 TI - Determination of metal content in three types of human gallstone. PMID- 2923994 TI - Copper uptake and regulation in a copper-tolerant decapod Cambarus bartoni (Fabricius) (Decapoda, Crustacea). PMID- 2923995 TI - Metal concentrations in pearl oyster, Pinctada radiata, collected from Saudi Arabian coast of the Arabian Gulf. PMID- 2923996 TI - Influence of variations in culture medium on the survival and reproduction of Daphnia magna. PMID- 2923997 TI - Toxicity of dimethoate to Daphnia magna and freshwater fish. PMID- 2923998 TI - Field studies on the impact of a new benzoylphenylurea insect growth regulator (UC-84572) on selected aquatic nontarget invertebrates. PMID- 2923999 TI - Acute toxicity of PAH contaminated sediments to the estuarine fish, Leiostomus xanthurus. PMID- 2924000 TI - Effects of selenium and mercury on glutathione and glutathione-dependent enzymes in experimental quail. PMID- 2924001 TI - Toxic effect of fenvalerate on fructose-1,6-diphosphate aldolase activity of liver, gill, kidney, and brain of the fresh water teleost, Tilapia mossambica. PMID- 2924002 TI - Pesticide residues in spray aircraft tank rinses and aircraft exterior washes. PMID- 2924003 TI - Fenvalerate interception by and dissipation from sugarcane foliage as affected by application technology. PMID- 2924004 TI - Measurement of aminocarb in long-distance drift following aerial application to forests. PMID- 2924005 TI - Residues of organochlorine insecticides in Delhi vegetables. PMID- 2924006 TI - Pesticide residues in edible oils and oil seeds. PMID- 2924007 TI - Pesticide residues in Arizona peregrine falcon eggs and prey. PMID- 2924008 TI - Photodecomposition of o-chloroaniline in aqueous solution with low pressure mercury lamp. PMID- 2924009 TI - Mercury in the Calcasieu River/Lake Complex, Louisiana. PMID- 2924010 TI - Effects of the water-soluble fractions of No. 2 fuel oil on the cytokinesis of the quahog clam (Mercenaria mercenaria). PMID- 2924011 TI - Nickel uptake and regulation in a copper-tolerant decapod, Cambarus bartoni (Fabricius) (Decapoda, Crustacea). PMID- 2924012 TI - [Ultrastructure of microcalcifications of the pulp mesenchyme of human deciduous teeth]. AB - Scanning electron microscopic observations of pulp calcifications in deciduous molars were correlated with microradiographic findings. Numerous spherical calcifications were found in appearance similar to those in the permanent dentition. In a second type, mineralization took the form of diffuse deposits of calcium. The discrete diffuse foci coalesced into large islands of mineralized connective tissue. A third type of calcification was observed in which rhombic crystals were associated in a spherulitic pattern. The exact cause of the crystal formation is unknown. Moreover, as we are aware, the spherulitic calcifications have never been previously reported in this location. The preliminary results indicated that mineralization in the pulp of deciduous molars, takes a variety of forms, suggesting that calcium deposition can occur by different processes. PMID- 2924013 TI - [Epidemiologic survey of orodental health in Fada N'Gourma (Burkina Faso)]. AB - In 1983 an investigation involving a homogeneous population sample from a western city of Burkina Faso has been performed in 1983 in order to estimate the oral health status of the population cut off from any dental assistance and to assess the importance of traditional practices in the city. The investigation, performed using World Health Organization techniques (WHO, 1977) involved 354 subjects, male and female, divided into age groups from 10 to 54. It was shown that: although the oral hygiene level was very low and no dental treatments were performed, caries level was very low--although gingivitis rate was high, advanced periodontitis rate was low--the frequency of interincisive diastema (one subject out of 4 in the 15-19 age group), the progressive decline of tooth cutting, a traditional practice, in town people but the large extent of cola use (one adult out of two). The present data will be used as base-line reference to evaluate the incidence of a dental care and prevention program which has just started in the same city of Burkina Faso. PMID- 2924014 TI - [The role of tea consumption in dental fluorosis in Jordan]. AB - 2,516 children of both sexes, six to fourteen years old, were examined in Jordan in the course of an epidemiological study. 81.11% of girls and 76.43% of boys presented severe forms of dental fluorosis according to DEAN's index. Drinking water analysis revealed fluoride concentrations ranging from 0.27 to 1.4 mg F/l. These concentrations are neighbouring optimum tolerated fluoride supplementation in drinking water. However high annual temperature mean and ten hours daily sunshine must also be taken in consideration. For social and climatic reasons, Jordanian children drink daily high quantities of tea. Analysis of tea prepared on jordanian way revealed a concentration of 1.2 mg F/l. This continuous intake of fluoride might explain the high severity of dental fluorosis in Jordan. PMID- 2924015 TI - [In vitro enamel fluoridation using an ultraviolet laser]. AB - 28 samples of human enamel have been studied in order to measure fluoride absorption after treatment with ultraviolet radiations. Samples treated with topical application only presented limited fluoride absorption in enamel surface (up to 0.5 microns deep). The absorption rate was higher, using an U.V. lamp. In samples treated with "excimer" laser, fluoride absorption was much higher in the surface layer and occurred also deeper (3 microns). PMID- 2924016 TI - [Incorporation of 3H-cortisol into the dental pulp and the induced changes]. AB - The incorporation of labelled hydrocortisone (3H-cortisol) in the dental pulp of Wistar rats has been tested using autoradiography. Light microscopy showed that an hour after injection the hormone is incorporated in the nuclei of the odontoblasts, subodontoblastic and endothelial cells of the dental pulp. It was also demonstrated at the ultrastructural level that a 4 week-treatment with high rates of hydrocortisone (16 and 32 mg/kg) at the time of rat intensive growth induces degeneration of the odontoblasts, pulp connective tissue cells and capillaries. High rates of hydrocortisone thus induces a decrease in the protective and reparative responses of rat molar pulp. PMID- 2924017 TI - [Structural, ultrastructural and microanalytical study of multiple enamel pearls]. AB - Numerous enamel drops and compound enamel pearls were found on the radicular proximal faces of maxillary molars and mandibular third molars of a young woman. Enamel and dentin of compound pearls as well as cementum next to drops and pearls presented the same structure and ultrastructure as enamel, dentin and cementum of the corresponding teeth. Microanalysis did not reveal differences between enamel of the mother tooth and enamel of drops and pearls. The enamel drops had no incremental growth lines. Cementum next to enamel drops and compound enamel pearls was acellular and covered occasionally with a thick layer of cellular cementum. Only enamel drops were partially covered by acellular cementum. Close to the enamel drops and at their surface, numerous fusing globular calcifications were observed. Formation of enamel drops and compound enamel pearls on dental root surfaces is rare. The simultaneous presence of numerous enamel drops and some compound enamel pearls on several roots of molars in the same denture seems to be an exceptional phenomenon. The involved factors inducing enamel formation remain still unknown. The multitude of both enamel drops and compound enamel pearl might be due to constitutional predisposition. PMID- 2924018 TI - Context-dependent associations in linear distributed memories. AB - In this article we present a method that allows conditioning of the response of a linear distributed memory to a variable context. This method requires a system of two neural networks. The first net constructs the Kronecker product between the vector input and the vector context, and the second net supports a linear associative memory. This system is easily adaptable for different goals. We analyse here its capacity for the conditional extraction of features from a complex perceptual input, its capacity to perform quasi-logical operations (for instance, of the kind of "exclusive-or"), and its capacity to structurate a memory for temporal sequences which access is conditioned by the context. Finally, we evaluate the potential importance of the capacity to establish arbitrary contexts, for the evolution of biological cognitive systems. PMID- 2924019 TI - Stability of symmetric idiotypic networks--a critique of Hoffmann's analysis. AB - Hoffmann (1982) analysed a very simple model of suppressive idiotypic immune networks and showed that idiotypic interactions are stabilizing. He concluded that immune networks provide a counterexample to the general analysis of large dynamic systems (Gardner and Ashby, 1970; May, 1972). The latter is often verbalized as: an increase in size and/or connectivity decreases the system stability. We here analyse this apparent contradiction by extending the Hoffmann model (with a decay term), and comparing it to an ecological model that was used as a paradigm in the general analysis. Our analysis confirms that the neighbourhood stability of such idiotypic networks increases with connectivity and/or size. However, the contradiction is one of interpretation, and is not due to exceptional properties of immune networks. The contradiction is caused by the awkward normalization used in the general analysis. PMID- 2924020 TI - Memory but no suppression in low-dimensional symmetric idiotypic networks. AB - We present a new symmetric model of the idiotypic immune network. The model specifies clones of B-lymphocytes and incorporates: (1) influx and decay of cells; (2) symmetric stimulatory and inhibitory idiotypic interactions; (3) an explicit affinity parameter (matrix); (4) external (i.e. non-idiotypic) antigens. Suppression is the dominant interaction, i.e. strong idiotypic interactions are always suppressive. This precludes reciprocal stimulation of large clones and thus infinite proliferation. Idiotypic interactions first evoke proliferation, this enlarges the clones, and may in turn evoke suppression. We investigate the effect of idiotypic interactions on normal proliferative immune responses to antigens (e.g. viruses). A 2-D, i.e. two clone, network has a maximum of three stable equilibria: the virgin state and two asymmetric immune states. The immune states only exist if the affinity of the idiotypic interaction is high enough. Stimulation with antigen leads to a switch from the virgin state to the corresponding immune state. The network therefore remembers antigens, i.e. it accounts for immunity/memory by switching between multiple stable states. 3-D systems have, depending on the affinities, 9 qualitatively different states. Most of these also account for memory by state switching. Our idiotypic network however fails to account for the control of proliferation, e.g. suppression of excessive proliferation. In symmetric networks, the proliferating clones suppress their anti-idiotypic suppressors long before the latter can suppress the former. The absence of proliferation control violates the general assumption that idiotypic interactions play an important role in immune regulation. We therefore test the robustness of these results by abandoning our assumption that proliferation occurs before suppression. We thus define an "escape from suppression" model, i.e. in the "virgin" state idiotypic interactions are now suppressive. This system erratically accounts for memory and never for suppression. We conclude that our "absence of suppression from idiotypic interactions" does not hinge upon our "proliferation before suppression" assumption. PMID- 2924021 TI - Automata network theories in immunology: their utility and their underdetermination. AB - Small networks of threshold automata are used to model complex interactions between populations of regulatory cells (helpers and suppressors, antigen specific and anti-idiotypic) which participate in the immune response. The models, being discrete and semiquantitative, are well adapted to the situation of incomplete information often encountered in vivo. However, the dynamics of many different network structures usually end up in the same attractor set. Thus, many different theories are equivalent in their explicative power for the same facts. This property, known as underdetermination of the theories by the facts, is given a quantitative estimate. It appears that such an underdetermination, as a kind of irreducible complexity, can be expected in many in vivo biological processes, even when the number of interacting and functionally coupled elements is relatively small. PMID- 2924022 TI - An alternative procedure for calculating glucose consumption from 2-deoxyglucose uptake. AB - In the commonly used model (Sokoloff) for the transport and metabolism of glucose and 2-deoxyglucose in brain tissue a novel choice of constant parameters is proposed. In particular the maximal transport capacity for glucose is assumed proportional to the rate of glucose consumption. The proportionality factor, the "transport factor", may be calculated from the lumped constant and is more likely than the latter to remain constant under varying conditions. Calculations founded on these considerations should yield results similar to the Sokoloff procedure in many situations, but differences appear when the arterial glucose concentration changes. The model is flexible and allows changes. PMID- 2924023 TI - Some simple statistical tests for exploring single-case time-series data. AB - Statistical analysis of single-case time-series data has received considerable attention. Many of the techniques discussed in the literature require long series of data or sophisticated statistical techniques. The present paper describes a number of 'quick and dirty' non-parametric tests which can be applied to relatively short time series. These tests require minimal calculations and can be carried out by inspecting graphical plots of the data. Each test is illustrated and tables for significance testing have been worked out. The importance of these tests lies in their potential to facilitate the accurate description of time series data. They are recommended as techniques for exploratory data analysis, the philosophy of which parallels Sidman's (1960) 'data led' approach to experimentation. PMID- 2924024 TI - Schizophrenic inability to judge facial emotion: a controlled study. AB - The ability of schizophrenics to judge facial emotion was examined using a new test derived to remedy methodological inadequacies in previous studies. The derivation procedure of the test is described. Five groups of 20 subjects each took part: acute schizophrenics, chronic schizophrenics, schizophrenics in remission, in-patients with depressive illness and normal subjects. They were asked to make a dichotomous emotion judgement ('happy' or 'sad') about a set of photographed faces: and then to make a dichotomous non-emotion judgement ('old' or 'young') on a set of photographs chosen from the same original pool to form a task of equal difficulty and discriminating ability. It was predicted, from previous studies, that acute schizophrenics would be specifically impaired on judging emotional expression in faces. Instead, they were found to be impaired on both an emotion and a non-emotion task on photographs of faces when these tasks were matched for difficulty and discriminating ability. They were significantly worse than remitted schizophrenics and normal subjects for both tasks, and for emotion, significantly worse then depressed subjects as well. The findings are considered in the light of current theories of visual processing in schizophrenia and of the neuropsychology of face processing. PMID- 2924025 TI - Factors of schizoid personality. AB - The increasing use of schizoid personality scales with normals has led to a number of validation studies, but to date there are no published analyses of the factorial structure of these scales. This study presents results of factor analyses of schizoid personality scales in an initial attempt to delineate their factorial structure. Questionnaires were administered to 114 male and female undergraduates and factor analysed using Varimax, Quartimax, and Oblique rotations. A two-factor varimax solution yielded a first factor accounting for 49 per cent of total unrotated variance with high (0.70 to 0.91) loadings from Hallucinatory predisposition, Perceptual aberration, Schizophrenism, STA and STB scales, and was interpreted as reflecting a general factor of schizoid personality disorder. Psychoticism and Social anhedonia loaded on a second factor accounting for 20 per cent of the variance which was uncorrelated (r = 0.09) with factor 1. This factor solution was closely replicated using quartimax and oblimin rotation criteria. It is concluded that Social anhedonia and Psychoticism represent a separate dimension from other scales which reflect the more positive features of schizoid personality. PMID- 2924026 TI - Psychosocial factors in Parkinson's disease. AB - Self-report measures were administered to 136 patients with Parkinson's disease in order to explore the relationships between aspects of psychological adjustment (depression, positive affect and acceptance of illness) and physical illness (duration of the illness, stage of illness and functional disability). Many psychosocial variables which, it was hypothesized, might intervene in the relationship between physical and psychological status were also measured. These were coping style, social support, self-esteem, attributions about the onset and course of the illness, perceived control and previous psychiatric history. A variable pattern of relationships between the different indices of psychological adjustment and physical illness emerged. Self-esteem, coping style and practical support contributed significantly to the variance in psychological adjustment. It was concluded that well-being in Parkinsonian patients is not exclusively dependent on a simple relationship between disability and depression, and that other factors should be taken into account in the clinical management of the illness. PMID- 2924027 TI - The relation between subjective and objective memory impairment after stroke. AB - The aim of this study was to examine the relationship between subjective memory and objective assessment using a test designed to reflect daily life memory skills, the Rivermead Behavioural Memory Test (RBMT). A total of 78 patients was assessed seven months after a stroke. Each patient completed a questionnaire about memory problems experienced in daily life. A relative or close friend completed the same questionnaire about the patient. Each patient was assessed on the RBMT and some conventional memory tests. Questionnaire responses were more highly correlated with the RBMT than with conventional tests of memory. PMID- 2924028 TI - Retrieval from semantic memory using meaningful and meaningless constructs by depressed, stable bipolar and manic patients. AB - Eleven depressed, 11 stable bipolar and six manic patients, 20 normals and eight late middle-age normals were tested for speech production using a word-fluency task. Fluency was prompted by either a letter (a relatively automatic task), or a semantic category (an effort-demanding task). The results showed that depressed patients were more impaired in speech production than other patients when prompted by a semantic category than when prompted by a letter. A post hoc matched-tasks check suggested that this finding was not due to differences in discriminating power between the two word-fluency tasks. Manic and stable bipolar patients did not differ in their speech production, although matched on age. The results suggest that depressives perform better on more automatic than on effort demanding tasks, and that manic and stable bipolar patients do not differ in speech production when experimentally imposed restrictions are present. PMID- 2924029 TI - Mood state-dependent retention using identical or non-identical mood inductions at learning and recall. AB - The most directly relevant evidence in favour of mood state-dependent retention (SDR) has confounded matching of mood at learning and recall with matching of mood-induction procedure. In this study 157 college students participated in a two (same vs. different mood at learning and free recall of neutral words) by two (same vs. different type of mood induction at learning and recall) experiment. Recall did not significantly differ among the groups. Use of neutral material might have precluded finding effects of mood on memory, but neutral material is optimal for separating mood SDR from mood-congruent retrieval. PMID- 2924030 TI - The relationship between cognitive failure and self-focused attention. AB - The Cognitive Failures Questionnaire and the Self-Consciousness Scale were administered to a sample of undergraduate students. The Private Self Consciousness and Social Anxiety subscales were significantly correlated with CFQ, suggesting that dispositional self-focused attention may be one underlying cause of cognitive failure. Similarities in the relation between CFQ, SCS and task performance are discussed. PMID- 2924031 TI - Colour naming of violence-related words in Northern Ireland. AB - To investigate the hypothesis that people in Northern Ireland are using denial to cope with the impact of political violence, a specially designed version of the Stroop test was developed. English students living in Northern Ireland evidenced significantly greater interference on the Violent Stroop compared to either English students living in England or Northern Irish students living in Northern Ireland suggesting that while the Northern Irish natives had habituated to the violence the English students living in Northern Ireland had not yet done so. PMID- 2924032 TI - Trait anxiety and coping style as predictors of pre-operative anxiety. AB - A situationally specific measure of trait anxiety based on the Endler model was a better predictor of pre-operative state anxiety than the STAI trait anxiety scale in 54 patients undergoing colonoscopy. Lower self-reported pre-operative anxiety was found for (a) repressors, who report low trait anxiety and high defensiveness on the Marlowe-Crown scale, than for (b) truly low anxious patients, who report low trait anxiety and low defensiveness. PMID- 2924033 TI - Research into schizophrenia. PMID- 2924034 TI - Unusual localization of cutaneous chronic graft-versus-host disease in the radiation fields in four cases. AB - Chronic graft-versus-host disease (GVHD) is a very heterogeneous entity with variable clinical expression. The pathophysiology involves autoimmune disorders and features of fibrosis. Four patients transplanted for severe aplastic anaemia conditioned with cyclophosphamide and thoraco-abdominal irradiation developed skin scleroderma specifically localized in the irradiation fields. This syndrome was remarkable for its late onset and the absence of factors known to trigger chronic GVHD. It is postulated that irradiation used in this protocol may induce keratinocyte damage and trigger chronic GVHD. PMID- 2924035 TI - Behaviour therapy in the rehabilitation of brain-injured individuals. PMID- 2924036 TI - Vocational evaluation of traumatic brain injury patients using the functional assessment inventory. AB - Impaired work capacity is one of the most common residual impairments encountered after either a severe or moderate traumatic brain injury (TBI), yet no instrument is available for screening TBI victims regarding their readiness to participate in more comprehensive vocational planning and evaluation. In the study reported here, the Functional Assessment Inventory (FAI) was administered to 76 subjects who suffered a moderate or severe TBI and the results obtained were compared to the Rancho Los Amigos Hospital Levels of Cognitive Functioning, the Mini-Mental State and the Glasgow Outcome Scale for sensitivity in discerning vocational readiness. The results obtained indicated that the FAI composite score has the greatest discriminating power in screening the vocational readiness of this population, followed by the Glasgow Outcome Scale. In addition, the FAI cluster scores demonstrated reasonable discriminative ability, which may prove useful in directing ongoing remediation. PMID- 2924037 TI - The response styles of post-acute traumatic brain-injured patients on the MMPI. AB - A retrospective descriptive study (n = 44) was conducted on the response styles of post-acute traumatic brain-injured patients on the MMPI. The sample profiles were examined on indices of consistency, random responding, and bias to look good or bad. The results showed that about 20% of the profiles were markedly inconsistent, including two profiles which met the criteria for random responding. Depending on the cut-off score used, between 0 and 9% were identified as biased to look bad, while between 18 and 30% were identified as biased to look good. A mean profile on the primary clinical and research scales was developed and a frequency count of the high two-point codes was conducted. This profile approached clinically significant levels on the Psychopathic deviant, Schizophrenia, Depression, and Mania scales, respectively. The three most frequently occurring two-point codes (2-4, 4-8, and 4-9) have been classified as characterological in nature. The primary implication of these results for clinicians was the need for careful scrutiny of indices of consistency, random responding and bias to look good when interpreting self-report measures such as the MMPI with the TBI population. PMID- 2924038 TI - Aphemia associated with bilateral striato-capsular lesions subsequent to cerebral anoxia. AB - A case is presented of a 13-year-old right-handed male who exhibited bilateral striato-capsular lesions following an episode of cerebral anoxia and a range of clinical features typical of aphemia. The findings of a neurological assessment, neuroradiological assessment and battery of speech/language tests are described and their implications for current theories regarding the role of the basal ganglia in speech/language function discussed. The patient initially demonstrated an isolated loss of the ability to articulate words without the loss of the ability to write or comprehend spoken language. His initial mutism later resolved into a dysarthria with features similar to those seen in hypokinetic dysarthria. It was concluded that striato-capsular lesions in childhood are capable of producing temporary language disturbances and in some cases a persistent dysarthria. PMID- 2924039 TI - Processing of pragmatic and facial affective information by patients with closed head injuries. AB - Although several affective impairments have been demonstrated to occur following closed-head injury (CHI), deficits of the communicative function of language, particularly sentenial and suprasentential pragmatic aspects, have been suggested, but not demonstrated, to occur. This study compared 31 normals and 31 severely closed-head injured patients matched for age, sex and education. The dependent measures consisted of a facial test of emotion (FTE) and a contextual test of emotion (CTE). The former task consisted of 36 slides representing facial expressions of the six emotions demonstrated by Ekman and colleagues to be transcultural, namely, job, sadness, fear, anger, surprise and disgust. The subject was required to name the appropriate emotion for each slide. The latter task consisted of correctly identifying the appropriate emotion for each of 36 brief verbal narratives representing contexts connotative of the same six transcultural emotions. The CHI patients were impaired overall on the FTE but not the CTE. However, the ability to identify anger was significantly impaired on both tasks when considered in isolation from the other emotions. It was concluded that a processing deficit of primary emotional material, particularly anger, does exist following CHI, but that this deficit is not necessarily independent of task and/or modality parameters. It was also concluded that evidence of a pragmatic deficit of the language function following CHI remains to be provided at this time. PMID- 2924040 TI - Hypothermia and severe head injury. AB - Two patients who were deeply unconscious (GCS = 4) following head injuries, sustained whilst intoxicated with alcohol, became hypothermic due to cold exposure. Despite negative prognostic factors both underwent craniotomy and evacuation of large acute subdural haematoma. After intensive postoperative management and rehabilitation both have made satisfactory recoveries. The contribution of hypothermia to their unpredicted favourable outcome is discussed, and the importance of recording temperature in head-injured patients is emphasized. PMID- 2924041 TI - Heterotopic bone formation involving wrist and fingers in brain-injured patients: a report of three cases. AB - Periarticular new bone formation is frequently observed in patients with prolonged coma, usually affecting large joints such as shoulders, elbows and hip joints. Unusual locations of PNBF involving the wrist and the inter-phalangeal joints are described in three patients who were in coma due to anoxic or traumatic brain insults. In each case flexor ankylosing positions were the end result. PMID- 2924042 TI - Acute subdural haematoma mimicking an epidural haematoma on a CT scan. AB - This paper reports an acute subdural haematoma mimicking an epidural haematoma as seen on a non-enhanced computerized tomography (CT) scan of the head in a patient who had sustained a traumatic head injury. The patient had undergone a craniotomy 4 years prior to the injury described here. PMID- 2924043 TI - Comparing motivational systems with two non-compliant head-injured adolescents. AB - Behavioural contracting, point systems and point systems plus response costs were compared to determine their effectiveness in increasing the attendance of two head-injured adolescents at class and therapy sessions. All of the motivational systems increased attendance, although the point system plus response cost seemed slightly more effective for one client. PMID- 2924044 TI - Behavioural and cognitive changes in traumatic brain injury: a spouse's perspective. AB - A single case study is presented that reviews the behavioural and emotional changes in a traumatic brain injury patient from the perspective of the spouse. PMID- 2924045 TI - Catastrophic case management: thoughts from a teacher/consumer/advocate. PMID- 2924046 TI - What changes will medical equipment managers face in the next five years?. Interview by Michael J. Miller. PMID- 2924047 TI - Productivity measurement: taking the first steps. PMID- 2924048 TI - A practical introduction to databases: Part 1. PMID- 2924049 TI - Quality assurance in transition. PMID- 2924050 TI - Semiautomatic algorithm to remove resonance artifacts from the direct radial artery pressure. AB - Resonance artifacts introduced by the catheter-manometer system are removed from the direct radial artery pressure using a three-step algorithm. First, the fast flush method is used to identify the natural frequency and damping coefficient of the monitoring system by digitizing and analyzing the pressure transient created by the flush. Second, resistor, capacitor, and inductor values are found for an RLC second-order model of the catheter-manometer system in use. Third, the algorithm predicts the undistorted radial artery pressure, removing the resonance artifacts by inverse-filtering the digitized monitored pressure waveform using the RLC circuit derived previously. The algorithm was implemented using a personal computer, but it could also be used without the computer by incorporating an analog-to-digital convertor and a microprocessor in the hemodynamic monitor. PMID- 2924051 TI - Design of a data-acquisition system for monitoring sleep organization in preterm infants. AB - A portable data-acquisition system suitable for long-term noninvasive monitoring of physiologic and behavioral variables in preterm infants is described. The system includes two video cameras, a video screen-splitter and amplifier, a time lapse video recorder, a microphone, a force-responsive transducer, an analog signal conditioner, and two microcomputers. One microcomputer, located in the neonatal intensive care unit (NICU) acquires electrophysiologic signals and preprocesses data in real time, during a continuous 48-hour session. After each session, the data file is transferred by telephone line to the other microcomputer, located in a laboratory, for editing, reduction, display, and final analysis. This arrangement enables noninvasive and nonintrusive monitoring, which is crucial for long-term recording of sleep-wake state organization of preterm infants. PMID- 2924052 TI - Experimental laboratory lithotripter: design, construction, and operation. AB - A laboratory lithotripter has been constructed and used to comminute (crush to a powder) both kidney stones and gallstones. The stones are placed in the second focus (f2) of an ellipse of revolution whose linear eccentricity is 4.7 cm and then acoustically shocked an average of 200 times by an underwater spark discharge at the first focus (f1). The energy levels available from the capacitors (3 to 52 joules) of this unit extend below and above the range of commercially available clinical devices. The electrical and mechanical design of this unit is presented. At a relatively low cost (approximately $15,000) the unit appears to have considerable application in non-clinical research in lithotripsy. Quantitative results of the application of this device to the comminution of human kidney stones are presented. PMID- 2924054 TI - Clinical engineering in clinical departments: a different point of view. PMID- 2924053 TI - A simple and inexpensive method for measuring electrosurgical variables. AB - A simple circuit that demodulates the high-frequency output of an electrosurgical generator to proportional DC values can be employed to monitor generator voltage and electrosurgical current. An example of the use of the circuit in a urologic application is given. Employing this monitoring circuit, quantitative comparisons of electrosurgical equipment and performances can be made. PMID- 2924055 TI - Electronics fundamentals: series capacitors. PMID- 2924056 TI - Should U.S. leakage current limits conform to the international standard? PMID- 2924057 TI - AIDS care team. PMID- 2924058 TI - Sex reassignment surgery. PMID- 2924059 TI - Early retirement. PMID- 2924060 TI - Ciprofloxacin. AB - Ciprofloxacin is a useful, orally available, non-toxic broad-spectrum antibiotic. Despite its novel mode of action, resistance is arising and we feel the drug should be reserved for specific indications where it can be of enormous value. PMID- 2924061 TI - Pulmonary tumour emboli mimicking pulmonary thromboemboli in a young woman. PMID- 2924062 TI - Excision of a pancreatic pseudocyst causing dysphagia. PMID- 2924063 TI - Streptococcus bovis endocarditis and carcinoma of the colon. PMID- 2924064 TI - The role of intraoperative salvage autotransfusion. PMID- 2924065 TI - Aetiology of alcohol dependence in women. PMID- 2924066 TI - Magnetic resonance imaging of the abdominal aorta. PMID- 2924067 TI - Inhibition of noradrenaline release by omega-conotoxin GVIA in the rat tail artery. AB - 1. The perivascular nerves of isolated tail arteries from Wistar rats were stimulated with field pulses (1 Hz, 2 pulses, every 2 min). omega-Conotoxin 10 nmol l-1 depressed neurogenically mediated contractions, but did not influence the contractions to noradrenaline 0.1-0.3 mumol l-1. 2. The inhibitory effect of omega-conotoxin was concentration-dependent (IC50 = 3.8 nmol l-1). It did not reach a steady-state during 30 min incubation and could not be reversed upon subsequent washout for another 60 min. 3. A gradual increase in the Ca2+ concentration of the medium from 1.25 mmol l-1 to 10 mmol l-1 enhanced vasoconstriction and attenuated the action of omega-conotoxin 10 nmol l-1. When a low stimulation intensity (120 mA) was used at high external Ca2+ (10 mmol l-1), similar contractile responses were obtained as under normal conditions (200 mA current, 2.5 mmol l-1 Ca2+). However, the inverse relationship between the effect of the toxin and external Ca2+ remained unchanged. 4. The time-course and degree of the inhibition by omega-conotoxin 3 nmol l-1 was identical in tail arteries of spontaneously hypertensive rats (SHR) and their normotensive controls (WKY). 5. When tail arteries of Wistar rats were preincubated with [3H]-noradrenaline, field stimulation (0.4 Hz, 24 pulses, every 16 min) evoked tritium overflow and vasoconstriction. omega-Conotoxin 30 nmol l-1 inhibited both responses to a similar extent. 6. Our results suggest that omega-conotoxin selectively blocks Ca2+ channels in the terminals of perivascular nerves and thereby reduces the release, but not the contractile effect of the sympathetic transmitter. PMID- 2924068 TI - Pharmacokinetics and dromotropic activity of ajmaline in rats with hyperthyroidism. AB - 1. The pharmacokinetics and the dromotropic action (increased PQ interval) of intravenously administered ajmaline (2 mg kg-1) were studied in hyperthyroid rats with sinus tachycardia. The hyperthyroidism was induced by intraperitoneal injection of 3,5,3'-triiodo-L-thyronine (0.5 mg kg-1) for 4 days. 2. The change in the ajmaline concentration in whole blood could be described by a biexponential equation. The steady state distribution volume of ajmaline decreased from 4.81 l kg-1 in control rats to 3.80 l kg-1 in hyperthyroid rats and the total body blood clearance was slightly higher in hyperthyroid rats than in control rats. 3. Ajmaline exhibited a saturable binding to rat plasma proteins, and one kind of binding site was found in the observed range of concentrations. The binding capacity was 2 fold higher in hyperthyroid rats than in control rats. 4. On the basis of the plasma unbound concentration, ajmaline exhibited an increased negative dromotropic activity in hyperthyroid rats compared with control rats. 5. A positive correlation was found between the pacing rate and the dromotropic action of ajmaline on atrioventricular conduction in isolated perfused hearts. There was no significant difference in the rate dependence of the effect of ajmaline on the heart between control and hyperthyroid rats. 6. Our findings suggest that the increased dromotropic activity of ajmaline is mainly due to the increased heart rate in hyperthyroid rats. PMID- 2924069 TI - Contractile responses to calcium chloride in rat aortic rings bathed in K+-free solution are resistant to organic calcium antagonists. AB - 1. In rat aortic rings, devoid of functional endothelium, suspended in a modified Krebs solution (KCl: 0 mM; CaCl2: 0.63 mM), addition of CaCl2 (0.89-10 mM) produced concentration-related increases in tension (Emax = 2.38 +/- 0.10 g, EC50 = 2.31 +/- 0.15 mM, n = 36). 2. The Ca2+ evoked contractile responses were not modified by cinnarizine (10 microM), diltiazem (1 microM), ryanodine (10 microM), verapamil (1 microM), or the dihydropyridines, nitrendipine (1 microM) and (-) Bay K 8644 (0.003-0.3 microM). 3. Cobalt chloride (0.1-1 mM) competitively antagonized the Ca2+ concentration-response curve; the Schild plot (slope 1.08 +/ 0.04), gave a pA2 value of 3.3 +/- 0.01 (n = 27). Nickel chloride (0.5-1 mM) displaced the Ca2+ concentration-response curve to the right, without an effect on the maximum response. Cadmium chloride (3-30 microM) depressed the maxima of concentration-response curves to Ca2+ with an IC50 of 15.5 +/- 1.1 microM (n = 6). 4. Monochlorobenzamil (100 microM), a Na+-Ca2+ exchange inhibitor, failed to modify the Ca2+-induced contractions. 5. In conclusion, Ca2+ evoked concentration related contractile responses of rat aortic rings bathed in a K+-free medium; these effects were attenuated by the divalent cations cobalt, nickel and cadmium, but not modified by several organic calcium antagonists. The lack of effect of diltiazem verapamil and the dihydropyridines would suggest that, under these experimental conditions, extracellular Ca2+ enters the cytosol via pathways which are distinct from the slow (L-type) calcium channels. PMID- 2924070 TI - The influence of ouabain on twitch potentiation by anticholinesterases in the phrenic nerve-diaphragm muscles of mice. AB - 1. (+)-Tubocurarine, hexamethonium, atropine, ouabain, and removal of potassium from the bathing medium were examined for their effects on indirectly evoked twitches (IT) of mouse phrenic nerve-diaphragm muscles in the presence or absence of neostigmine. 2. Neostigmine increased the amplitude of IT. The twitch potentiation was reduced by (+)-tubocurarine at low concentrations that had no inhibitory effect on normal IT. Hexamethonium (10-100 microM), but not atropine (0.1-1 microM), partially inhibited the twitch potentiation. Neither hexamethonium nor atropine had an inhibitory effect on IT in the absence of neostigmine. 3. Ouabain (5 microM) abolished the twitch potentiation by neostigmine while having no inhibitory effect on directly evoked twitches in the presence of neostigmine and (+)-tubocurarine together. 4. The potentiating effect of neostigmine was less in a potassium-free bathing solution. The inhibitory effect of ouabain disappeared in this solution. 5. Reinclusion of KCl at 2.5 mM restored both the potentiating effect of neostigmine and the antagonistic effect of ouabain. This reinclusion did not potentiate IT in the absence of neostigmine. 6. An interaction resembling that between ouabain and neostigmine was obtained between ouabain and physostigmine or paraoxon. 7. Both endplate potentials (e.p.ps) and miniature e.p.ps increased in terms of their amplitude and duration in the presence of neostigmine. Ouabain did not reduce the enhanced endplate responses. 8. These results indicate that the potentiation of IT by anticholinesterases may occur via nicotinic receptors which are sensitive to both (+)-tubocurarine and hexamethonium, and that the interaction between anticholinesterases and ouabain depends on the presence of K+. It appears that the mechanisms of twitch potentiation are dependent on the ionic gradients maintained by Na+-K+-ATPase. PMID- 2924071 TI - Muscarinic agonists and potassium currents in guinea-pig myenteric neurones. AB - 1. Intracellular electrophysiological recordings were obtained from single neurones of the guinea-pig myenteric plexus in vitro. Using single electrode voltage clamp techniques, four distinct potassium currents were described and the effects of muscarinic agonists on these currents were studied. 2. A calcium dependent potassium current (gKCa) was present in AH neurones at rest, and was much increased following a brief depolarization (50 ms, to 0 mV). Muscarinic agonists reduced both the resting current and the current evoked by depolarization. Pirenzepine competitively antagonized the suppression by muscarine of the calcium-dependent potassium current (or after-hyperpolarization) following an action potential. The dissociation equilibrium constant for pirenzepine was about 10 nM. 3. The conductance of AH neurones increased two to three fold when they were hyperpolarized negative to -90 mV. This inward rectification was blocked by extracellular caesium (2 mM) or rubidium (2 mM), but not by tetraethylammonium (TEA, 40 mM), 4-aminopyridine (100 microM) or cobalt (2 mM). The inward rectification was unaffected by muscarinic agonists. 4. When AH neurones were depolarized from very negative holding potentials (less than -80 mV) a brief outward current was recorded with a duration of about 200 ms. This transient or A current was completely blocked by 4-aminopyridine (100 microM) but was not affected by tetrodotoxin (300 nM), TEA (40 mM) or cobalt (2 mM). Muscarinic agonists did not affect the A current. 5. In S neurones, and in AH neurones in calcium-free solutions, the potassium conductance (in TEA and caesium) behaved according to constant field assumptions. This background conductance was suppressed by muscarinic agonists. 6. It is concluded that the depolarization by muscarinic agonists of myenteric AH neurones is due to a suppression of both a calcium-dependent potassium conductance and a background potassium conductance. Muscarinic depolarization of S neurones results only from suppression of the background potassium conductance. Effects on both conductances result from M1-receptor activation. Inward rectifying and transient outward (A) potassium currents are unaffected. PMID- 2924073 TI - 1,3,8- and 1,3,7-substituted xanthines: relative potency as adenosine receptor antagonists at the frog neuromuscular junction. AB - 1. The ability of 1,3,8-substituted xanthines (1,3-dipropyl-8-(4-(2 aminoethyl)amino)carbonylmethyloxyphenyl) xan thine (XAC), 1,3-dipropyl-8-(4 carboxymethyloxyphenyl)xanthine (XCC), 1,3-dipropyl-8-(2-amino-4 chlorophenyl)xanthine (PACPX), 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), 1,3 diethyl-8-phenylxanthine (DPX) and 8-phenyltheophylline (8-PT)), of 1,3,7 substituted xanthines (1-propargyl-3,7-dimethylxanthine (PGDMX) and caffeine), and of a 3-substituted xanthine (enprofylline) to antagonize the inhibitory effect of 2-chloroadenosine (CADO) on the amplitude of nerve-evoked twitches was investigated in innervated sartorius muscles of the frog. 2. All the 1,3,8 substituted xanthines, in concentrations virtually devoid of effect on neuromuscular transmission, shifted to the right, in a near parallel manner the log concentration-response curve for CADO. Linear Schild plots with slopes near to unity at concentration-ratios less than 14 were obtained for XAC, XCC, DPCPX, DPX and 8-PT. 3. The order of potency of the 1,3,8-substituted xanthines as antagonists of the effect of CADO was XAC (Ki = 23 nM) greater than or equal to DPCPX (35 nM) greater than 8-PT (200 nM) greater than or equal to DPX (295 nM) greater than XCC (1905 nM) greater than or equal to PACPX (2291 nM). No correlation was found between the potency of these xanthines as antagonists of the adenosine receptor at the frog neuromuscular junction and their reported potency as antagonists of the A1- or A2-adenosine receptors. 4. The 1,3,7 substituted xanthines, PGDMX and caffeine, in concentrations virtually devoid of effect on neuromuscular transmission, also caused parallel shifts to the right of the log concentration-response curves for CADO, but were less potent than the 1,3,8-substituted xanthines. PGDMX was more than 20 times more potent than caffeine. 5. Enprofylline in concentrations up to 100 microM did not antagonize the inhibitory effect of CADO on neuromuscular transmission. 6. It is concluded that the antagonist profile of the adenosine receptor mediating inhibition of transmission at the frog neuromuscular junction is different from the antagonist profile of the A1- and A2-adenosine receptors. PMID- 2924072 TI - Modulation by glycyrrhetinic acid derivatives of TPA-induced mouse ear oedema. AB - 1. The anti-inflammatory effects of glycyrrhetinic acid and its derivatives on TPA (12-O-tetradecanoylphorbol-13-acetate)-induced mouse ear oedema were studied. The mechanisms of TPA-induced ear oedema were first investigated with respect to the chemical mediators. 2. The formation of ear oedema reached a maximum 5 h after TPA application (2 micrograms per ear) and the prostaglandin E2 (PGE2) production of mouse ear increased with the oedema formation. 3. TPA-induced ear oedema was prevented by actinomycin D and cycloheximide (0.1 mg per ear, respectively) when applied during 60 min after TPA treatment. 4. Of glycyrrhetinic acid derivatives examined, dihemiphthalate derivatives (IIe, IIe', IIIa, IIIa', IVa, IVa') most strongly inhibited ear oedema on both topical (ID50, 1.6 mg per ear for IIe, 2.0 mg per ear for IIIa and 1.6 mg per ear for IVa) and oral (ID50, 88 mg kg-1 for IIe', 130 mg kg-1 for IIIa' and 92 mg kg-1 for IVa') administration. 5. Glycyrrhetinic acid (Ia) and its derivatives applied 30 min before TPA treatment were much more effective in inhibiting oedema than when applied 30 min after TPA. A dihemiphthalate of triterpenoid compound IVa completely inhibited oedema, even when applied 3 h before TPA treatment. 6. Glycyrrhetinic acid (Ia) and deoxoglycyrrhetol (IIa), the parent compounds, produced little inhibition by oral administration at less than 200 mg kg-1. 7. These results suggest that the dihemiphthalate derivatives of triterpenes derived from glycyrrhetinic acid by chemical modification are useful for the treatment of skin inflammation by both topical and oral application. PMID- 2924074 TI - Atenolol, but not mexiletine, protects against stimulus-induced ventricular tachycardia in a chronic canine model. AB - 1. In a placebo-controlled study of the antiarrhythmic and electrophysiological properties of atenolol and mexiletine, programmed electrical stimulation (PES) was performed in three groups of six conscious greyhounds, 7-30 days after coronary artery ligation. 2. In the placebo group, repeated PES challenge resulted in the consistent induction of ventricular tachycardias (VT) in 4/6 dogs and ventricular fibrillation in 2/6. Atenolol prevented arrhythmia induction in 4/6 dogs, one continued to demonstrate a VT and one died (P less than 0.05 compared with placebo). In the mexiletine group 5/6 dogs continued to demonstrate a VT and one died. 3. Electrocardiographic parameters were not affected by any treatment. There was no change in blood pressure in any group but when compared with placebo, heart rate fell (P less than 0.05) after atenolol (256 micrograms kg-1) and increased (P less than 0.05) after mexiletine (16 mg kg-1). Effective (ERP) and functional (FRP) refractory periods did not change after mexiletine, but ERP was prolonged (P less than 0.05) after atenolol. 4. The results indicate that atenolol but not mexiletine is effective in preventing re-entrant arrhythmias in this conscious canine model. Antiarrhythmic efficacy may be related to a fall in heart rate and/or a prolongation of refractoriness. PMID- 2924075 TI - Actions of the GABAB agonist, (-)-baclofen, on neurones in deep dorsal horn of the rat spinal cord in vitro. AB - 1. The electrophysiological actions of the GABAB agonist, (-)-baclofen, on deep dorsal horn neurones were studied using an in vitro preparation of the spinal cord of 9-16 day old rat. 2. On all neurones tested, (-)-baclofen (100 nM-30 microM) had a hyperpolarizing action which was associated with a reduction in apparent membrane input resistance. The increase in membrane conductance was dose dependent and had a Hill coefficient of 1.0. 3. The (-)-baclofen-activated hyperpolarization persisted in the presence of bicuculline (50 microM) and Mg2+ (20 mM). 4. The reversal potential of the hyperpolarizing event was estimated at 102 mV and was made less negative by increasing the external concentration of potassium ions. 5. Over the same concentration range, (-)-baclofen also depressed the polysynaptic composite excitatory postsynaptic potentials (e.p.s.ps) evoked in these neurones by electrical stimulation of the dorsal root entry zone. 6. The potassium channel blockers caesium, applied intracellularly, and barium, applied extracellularly, depressed the postsynaptic response to baclofen but not its effect on e.p.s.ps. 7. We propose that (-)-baclofen has more than one mechanism of action in spinal dorsal horn: a postsynaptic action mediated via an increase in potassium conductance and a presynaptic action that is not associated with potassium channels and may be mediated via calcium channels. Since previous studies have demonstrated little effect of (-)-baclofen on transmitter release in spinal cord, it is possible that the postsynaptic hyperpolarizing action of (-) baclofen may account for its clinical potency as an anti-spastic agent. PMID- 2924076 TI - An anti-inflammatory steroid inhibits tissue sensitization by IgE in vivo. AB - An anti-inflammatory corticosteroid, dexamethasone, was found to be a potent suppressor of cell sensitization induced by IgE antibody in a model of type I allergic inflammation in vivo. Low doses (approximately less than 10(-10) mol) of dexamethasone, administered intradermally to rabbits 90 min before injection of IgE into the same sites, suppressed local oedema induced by a local challenge with antigen 72 h later. The effect was not due to anti-inflammatory activity persisting in the skin site for the 3 day period. This novel potent activity of the corticosteroid may be an important component of its anti-allergic effect in diseases such as asthma. PMID- 2924077 TI - Effects of pertussis toxin on the behavioural and ECoG spectrum changes induced by clonidine and yohimbine after their microinfusion into the locus coeruleus. AB - 1. Pertussis toxin, a substance which interferes selectively with receptor mediated signal transduction mechanisms, was injected into the locus coeruleus of rats 1, 2, 3, 6 or 10 days before the microinjection of clonidine or yohimbine into the same site. 2. Clonidine produced in control rats typical behavioural sedation and/or sleep and ECoG synchronization while yohimbine produced behavioural arousal and ECoG desynchronization. 3. The behavioural and ECoG effects of both compounds were blocked in animals pretreated with pertussis toxin. This activity was more marked from 2 to 6 days after pertussis toxin pretreatment and was restored 10 days after toxin administration. In addition, the behavioural and ECoG slow-wave sleep observed after intraperitoneal administration of clonidine (0.2 mumol kg-1) was significantly reduced by prior (3 days) microinfusion of pertussis toxin into the locus coeruleus. 4. These results are consistent with the hypothesis that the behavioural and ECoG effects of clonidine and yohimbine are mediated via a guanine regulatory protein which is affected by pertussis toxin. PMID- 2924078 TI - Release of 5-hydroxytryptamine, dopamine and noradrenaline in the rat vas deferens in the presence of compound 48/80, veratridine or K+. AB - 1. The release of 5-hydroxytryptamine (5-HT), dopamine and noradrenaline (NA) from the rat isolated vas deferens was estimated by high performance liquid chromatography with electrochemical detection. 2. Compound 48/80, which is known to release 5-HT and histamine from mast cells, induced a concentration-related, rapid overflow of 5-HT from the rat isolated vas deferens, releasing about 50% of the 5-HT present in the tissue at a concentration of 300 micrograms ml-1. The drug did not induce the release of either dopamine or NA. 3. The depolarizing agents veratridine (10 microM) or K+ (100 mM) induced the release of 5-10% of the 5-HT present in the vas deferens, but did not evoke the overflow of 5-HT from isolated mast cells. 4. Veratridine induced the release of a greater proportion of the dopamine than of the NA contained in the vas deferens (41.0 +/- 5.5 vs 17.9 +/- 2.0%, after 20 min of exposure to the drug, n = 6). In contrast, K+ evoked the release of both amines equally. 5. It is concluded that in the rat vas deferens 5-HT is stored in mast cells and also in cells responsive to depolarizing stimuli. It is suggested that 5-HT could be a neuromodulator or a neurotransmitter in this organ. Veratridine and K+ induce the release of dopamine in addition to NA. PMID- 2924079 TI - Intragastric capsaicin enhances rat gastric acid elimination and mucosal blood flow by afferent nerve stimulation. AB - 1. This study investigated the effects of intragastric capsaicin on acid output, clearance of aniline, potential difference, and morphology of the mucosa in the rat stomach. The experiments were carried out on rats anaesthetized with urethane in which the stomachs were continuously perfused with saline. 2. When the stomach was perfused with normal saline (pH approximately 6), intragastric capsaicin (32 640 microM) had no effect on the output of titratable acid. In contrast, when acid output was stimulated by pentagastrin or when the stomach was perfused with acid saline (pH 3), capsaicin reduced acid output. Acid loss which occurred during perfusion with saline of pH 2 was not significantly increased by capsaicin. This suggests that capsaicin does not enhance acid back-diffusion but facilitates acid elimination by other means. 3. The gastric clearance of [14C] aniline, which is an indirect index of gastric mucosal blood flow, was estimated while the stomach was perfused with saline of pH 3. The clearance of aniline rose by 50-60% following intragastric administration of capsaicin (160 microM) whereas the mean arterial blood pressure was increased by about 2.5 mmHg only. Combined pretreatment of the rats with atropine, phentolamine, and propranolol did not alter the effect of capsaicin on the gastric clearance of aniline. 4. The gastric potential difference was not altered by capsaicin (160 microM) administered together with saline of pH 3. This and the finding that there were no signs of mucosal damage by light and scanning electron microscopy indicate that intragastric capsaicin does not irritate the gastric mucosa. 5. The effects of intragastric capsaicin on gastric acid output and aniline clearance and on blood pressure were absent in rats in which capsaicin-sensitive afferent neurones had been ablated by neonatal treatment with a neurotoxic dose of capsaicin, which indicates that they result from stimulation of afferent nerve endings in the stomach. It is concluded that facilitation of acid elimination and mucosal blood flow may contribute to the previously reported protective action of capsaicin on the gastric mucosa. PMID- 2924080 TI - The human astrocytoma cell line 1321 N1 contains M2-glandular type muscarinic receptors linked to phosphoinositide turnover. AB - 1. Muscarinic receptors present in the human astrocytoma cell line 1321 N1 were characterized in radioligand binding studies and in functional studies of carbachol-stimulated phosphatidylinositol (PI) turnover. 2. In radioligand binding studies the muscarinic receptor in intact cells could be labelled using [3H]-N-methylscopolamine ([3H]-NMS) but not by [3H]-pirenzepine. In the intact cells these receptors displayed low pirenzepine affinity (pKi = 6.83) indicating that they were not of the M1 subtype. Furthermore, the 1321 N1 muscarinic receptors displayed low affinity for the two M2-cardiac selective ligands methoctramine (pKi = 5.82) and AF-DX 116 (pKi = 6.29). This pharmacology was consistent with the 1321 N1 cells containing a single population of muscarinic receptors that displayed a similar pharmacology to the M2-receptor present in exocrine gland tissue. 3. The M2-gland nature of the receptors was further indicated in the functional studies where antagonist affinities were determined from their ability to antagonize carbachol-stimulated PI turnover in 1321 N1 cells. pA2 values for pirenzepine (7.31), methoctramine (6.10) and AF-DX 116 (6.52) were similar to those determined in the binding studies. 4. From these studies we conclude that 1321 N1 astrocytoma cells contain an M2-gland muscarinic receptor which mediates muscarinic receptor-mediated stimulation of PI turnover in these cells. PMID- 2924082 TI - Structure-activity relationships of new analogues of arecaidine propargyl ester at muscarinic M1 and M2 receptor subtypes. AB - 1. The potency of arecaidine propargyl ester (APE) and of several analogues containing a modified ester side chain has been assessed at M1 and M2 muscarinic receptor subtypes. APE was shown to act as a potent agonist at ganglionic M1 receptors in the pithed rat, at M2 receptors in guinea-pig isolated atria (-log EC50 = 8.22) and ileum (-log EC50 = 7.77). 2. The arecaidine 2-butynyl and 2 pentynyl esters were approximately equipotent with APE at M1 and M2 receptors, whereas the 2-hexynyl derivative was found to be less potent than APE in atria ( log EC50 = 6.80) and ileum (-log EC50 = 6.70) by about one order of magnitude. The 2-heptynyl and 3-phenyl propargyl esters exhibited no agonist actions in atria and ileum. 3. Shifting the triple bond from the 2 to the 3 position and introducing a bulky group at position 1 of the ester side chain of APE and analogues resulted in competitive antagonists (pA2 ranging from 4.9 to 7.3). 4. APE and its 2-butynyl analogue showed some agonistic selectivity for cardiac M2 receptors (potency ratio, ileum/atria = 2.8 and 4.6 respectively). All antagonists in this series of compounds were not selective in terms of affinity since their pA2 values at cardiac and ileal M2 receptors were similar (potency ratios, ileum/atria = 0.4 to 1.2). PMID- 2924081 TI - The classification of prostaglandin DP-receptors in platelets and vasculature using BW A868C, a novel, selective and potent competitive antagonist. AB - 1. BW A868C, a novel compound, behaved as a simple competitive antagonist in a human washed platelet aggregation assay. Anti-aggregatory concentration-effect curves to BW 245C were displaced in a parallel manner. The shifts accorded with a Schild plot slope of unity and a pKB of 9.26. 2. Inhibition of platelet aggregation by prostaglandin D2 (PGD2) was antagonized with a similar potency, as were the relaxation effects of BW 245C and PGD2 in the rabbit jugular vein. BW A868C can, therefore, be classified as a DP-receptor antagonist. 3. Actions of BW A868C at other prostaglandin receptors (IP, EP1, EP2, TP and FP) were excluded at concentrations up to 1,000 times higher than the DP-receptor affinity. 4. Analyses of BW 245C- and PGD2-mediated effects were complicated by additional agonist receptor interactions which were revealed by BW A868C. In rabbit jugular vein a resistant phase of agonism was detectable, indicating that both agonists exerted effects through another receptor (possibly EP2). Also, PGD2, in addition to its anti-aggregatory effect on platelets, demonstrated a pro-aggregatory action in the presence of BW A868C. 5. The contractile effects of PGD2 in guinea pig tracheal strips were resistant to 10 microM BW A868C indicating that they were not mediated through DP-receptors. 6. To our knowledge this is the first account of a well-classified competitive antagonist at the DP-receptor. Its potency and selectivity make it an important new tool in prostanoid receptor classification and identification. PMID- 2924083 TI - Pharmacological modulation of Paf-induced rat pleurisy and its role in inflammation by zymosan. AB - 1. The intrapleural injection of Paf-acether into rats caused, at 30 min, a marked exudation accompanied by a reduction in the pleural leucocyte count. At 6 h, the exudate volume had decreased and a significant increase in the total leucocyte count, particularly eosinophils was noted. 2. Two Paf-acether antagonists, WEB 2086 and 48740 RP abrogated the pleural leucopenia observed 30 min after Paf-acether administration, whereas the exudation was inhibited only by the former. Pleurisy was also reduced by about 60% with dexamethasone, by about 45% with BW 755C or LY 171883, a mixed cyclo-oxygenase/lipoxygenase inhibitor and a peptido-leukotriene antagonist respectively, and by about 30% with indomethacin, flurbiprofen or piroxicam. 3. Repeated daily intrapleural injections of Paf-acether led to a state of progressive desensitization to Paf acether itself, whereas responsiveness to 5-hydroxytryptamine was maintained. In addition, the Paf-induced auto-desensitization was largely inhibited by WEB 2086. 4. Pleurisy induced by zymosan, but not by carrageenin, was significantly reduced in Paf-acether-desensitized animals. These results were consistent with those obtained with WEB 2086 which suppressed zymosan-induced but not carrageenin induced pleurisy. 5. This study suggests that Paf-acether-induced pleurisy in the rat may be mediated by lipoxygenase arachidonic acid metabolites and that pleurisy induced by zymosan, but not by carrageenin, is largely dependent upon Paf-acether. PMID- 2924085 TI - Affinity of muscarinic receptor antagonists for three putative muscarinic receptor binding sites. AB - 1. A range of muscarinic receptor antagonists were examined for affinity at the M1 muscarinic binding site, present in rat cerebrocortical membranes and the M2 muscarinic binding sites of rat cardiac and submaxillary gland membranes. 2. The results obtained were consistent with the presence of three classes of muscarinic binding site. 3. Both the M1 binding site, labelled by [3H]-pirenzepine ([3H] Pir) in rat cerebrocortical membranes, and the M2 gland binding site, labelled by [3H]-N-methyl scopolamine ([3H]-NMS) in rat submaxillary gland membranes, displayed higher affinity for pirenzepine, dicyclomine, 4-diphenylacetoxy-N methylpiperidine methiodide (4-DAMP) and cyclohexylphenyl (2-piperidinoethyl) silanol (CPPS) than did the M2 binding sites of cardiac membranes labelled by [3H]-NMS. 4. The M2 cardiac sites displayed higher affinity for methoctramine, himbacine and AF-DX 116 than did either the M1 binding site of cerebrocortical membranes or the M2 gland binding site present in rat submaxillary gland membranes. 5. The M1 and M2 gland binding sites could only be distinguished by considering the absolute affinity of compounds for these two sites. Thus, all compounds, with the exception of 4-DAMP, displayed between a 2 and 8 fold higher affinity for the M1 than for the M2 gland binding site. There were no antagonists with higher M2 gland than M1 affinity. PMID- 2924084 TI - A specific inhibitor of nitric oxide formation from L-arginine attenuates endothelium-dependent relaxation. AB - 1. The role of L-arginine in the basal and stimulated generation of nitric oxide (NO) for endothelium-dependent relaxation was studied by use of NG-monomethyl L arginine (L-NMMA), a specific inhibitor of this pathway. 2. L-Arginine (10-100 microM), but not D-arginine (100 microM), induced small but significant endothelium-dependent relaxations of rings of rabbit aorta. In contrast, L-NMMA (1-300 microM) produced small, endothelium-dependent contractions, while its enantiomer NG-monomethyl-D-arginine (D-NMMA; 100 microM) had no effect. 3. L-NMMA (1-300 microM) inhibited endothelium-dependent relaxations induced by acetylcholine (ACh), the calcium ionophore A23187, substance P or L-arginine without affecting the endothelium-independent relaxations induced by glyceryl trinitrate or sodium nitroprusside. 4. The inhibition of endothelium-dependent relaxation by L-NMMA (30 microM) was reversed by L-arginine (3-300 microM) but not by D-arginine (300 microM) or a number of close analogues (100 microM). 5. The release of NO induced by ACh from perfused segments of rabbit aorta was also inhibited by L-NMMA (3-300 microM), but not by D-NMMA (100 microM) and this effect of L-NMMA was reversed by L-arginine (3-300 microM). 6. These results support the proposal that L-arginine is the physiological precursor for the basal and stimulated generation of NO for endothelium-dependent relaxation. PMID- 2924086 TI - Monoamine oxidase activity and triiodothyronine biosynthesis in human cultured thyroid cells. AB - 1. The proposal that monoamine oxidase (MAO) is a source of peroxide in thyroid hormone biosynthesis has been examined by use of isolated cultured human thyroid cells which retain the ability to secrete triiodothyronine (T3) in response to thyroid stimulating hormone (TSH). 2. The results demonstrated the presence of MAO A and B in human thyroid cells which oxidized 5-hydroxytryptamine and 2 phenylethylamine, respectively, and were selectively inhibited by the MAO inhibitors clorgyline and (-)-deprenyl. 3. Addition of propylthiouracil to the culture system induced a 61% reduction in TSH-stimulated T3 secretion, indicating that the bulk of such secretion apparently derives from de novo iodothyronine synthesis. 4. The MAO A and B substrate, tyramine, was ineffective in stimulating T3 secretion. 5. The selective MAO inhibitors, clorgyline and (-)-deprenyl, alone and in combination, and in the presence and absence of tyramine, failed to inhibit basal as well as TSH-stimulated T3 secretion in cultured human thyrocytes. 6. It is therefore apparent that even though thyroid MAO A and B enzyme reactions result in the generation of H2O2, this H2O2 does not seem to play a significant role in T3 biosynthesis. PMID- 2924087 TI - Ouabain distinguishes between nicotinic and muscarinic receptor-mediated catecholamine secretions in perfused adrenal glands of cat. AB - 1. The effect of ouabain on catecholamine (adrenaline and noradrenaline) secretion induced by agents acting on cholinoceptors was studied in perfused cat adrenal glands. Acetylcholine (ACh) (5 x 10(-7) to 10(-3) M), pilocarpine (10(-5) to 10(-3) M) and nicotine (10(-6) to 5 x 10(-5) M) caused dose-dependent increases in catecholamine secretion. Both ACh and nicotine released more noradrenaline than adrenaline and the reverse was the case for pilocarpine. 2. Ouabain (10(-5) M) enhanced catecholamine secretion induced by ACh (10(-5) M), pilocarpine (10(-3) M) and nicotine (3 x 10(-6) M) during perfusion with Locke solution. The ratio of adrenaline to noradrenaline was not affected by ouabain. 3. In the absence of extracellular Ca2+, ACh and pilocarpine, but not nicotine, still caused a small increase in catecholamine secretions, which were enhanced by treatment with ouabain (10(-5) M) plus Ca2+ (2.2 mM) for 25 min. The effect of ouabain was much more significant on noradrenaline secretion than on adrenaline secretion. The enhanced response was blocked by atropine (10(-6) M) but not by hexamethonium (5 x 10(-4) M). 4. Nifedipine (2 x 10(-6) M) inhibited the responses to pilocarpine and nicotine. The treatment with ouabain (10(-5) M) reversed only the response to pilocarpine and resulted in a significant increase in the proportion of noradrenaline released. 5. It is suggested that ouabain enhances evoked catecholamine secretions by facilitating Ca2+ entry through nicotinic receptor-linked Ca2+ channels and by increasing the intracellular Ca2+ pool linked to muscarinic receptors. PMID- 2924088 TI - Proceedings of the British Pharmacological Society. London, 19th-21st December. Abstracts. PMID- 2924089 TI - Accurate non-word spelling despite congenital inability to speak: phoneme grapheme conversion does not require subvocal articulation. AB - Previous work has shown that children with motor speech disorders (dysarthria) have no particular difficulty in spelling non-words containing sounds that they cannot produce accurately in their own speech. This suggests that subvocal articulation is not implicated in generating a graphemic representation from a phonological string. However, it could be argued that, although severely unintelligible, dysarthric individuals may be able to use their own articulation as a basis for translating between phonemes and graphemes. In this study we investigated spelling of words and non-words in cerebral palsied individuals, including speechless (anarthric) as well as dysarthric subjects. Although spelling abilities of these individuals were below control levels, there was no evidence that different processes were used, and one anarthric individual achieved perfect performance in spelling a list of non-words which included consonant clusters. It is concluded that spelling by the 'indirect' route can be achieved in the absence of any articulation. PMID- 2924090 TI - The memory structure of autistic idiot-savant mnemonists. AB - The memory organization of six autistic mnemonists was investigated in two experiments. The first of these provided some evidence that the material of special interest to the subjects, in the present instance bus numbers, was stored in memory in a categorized form. The second study showed that though the idiot savant mnemonists did not differ from controls in the level of their general memory performance, the factor structure of a number of memory tests differed between the groups. In contrast to the controls, a verbal memory factor which seemed independent of measured verbal IQ was operative in the mnemonist subjects. PMID- 2924091 TI - Radiological evaluation of temporal bone disease: high-resolution computed tomography versus conventional X-ray diagnosis. AB - Sixty-two patients with different temporal bone lesions were prospectively examined by high-resolution computed tomography (CT) and conventional plain radiography, including pluridirectional tomography. High-resolution CT enabled a clear diagnosis in 80% of cases, conventional radiology in 63%; 1.6-times more bone information was recorded by high-resolution CT which is clearly superior for imaging cholesteatomas, metastases and inflammatory processes and for evaluating osseous destruction. With regard to pathological soft tissue or effusions filling the tympanic cavities, conventional radiology shows poor sensitivity (0.61). High resolution CT is the most sensitive method for the imaging and classification of temporal bone fractures, including labyrinthine damage and ossicular chain injuries. Only in cases of atypical fractures with an unfavourable relationship to the CT planes, can carefully directed tomography be more effective. In most cases high-resolution CT replaces conventional radiology and should be the method of choice for comprehensive radiological examination of the temporal bone. PMID- 2924092 TI - Basic concepts of femoral neck anteversion: comparison of two definitions. AB - Femoral neck anteversion is determined by the neck, shaft and knee axes. It is commonly assumed that the neck axis is a straight line connecting the centre of the femoral head, the centre of the femoral neck and the axis of the femoral shaft. However, the line through the centre of the femoral head and neck crosses anterior to the axis of the femoral shaft. A distinction has therefore to be made between two principal different definitions of anteversion, denoted ANTEV 1 and ANTEV 2 in this paper, depending on the precise definition of the neck axis. Previous studies have indicated substantial differences between these definitions. The present study, using precise measuring methods, shows that the definitions have a systematic but small spread of differences. The large individual variation previously found between the two definitions is therefore caused mainly by the measuring methods and to a lesser extent by real anatomical variations. PMID- 2924093 TI - Percutaneous drainage of subphrenic abscesses. AB - Forty subphrenic abscesses were drained percutaneously in 37 patients. These abscesses were subsequent to abdominal surgery (28 patients), biliary obstruction and/or fistula (six patients), trauma (two patients) or acute pancreatitis (one patient). The procedures were usually monitored by duplex sonography and fluoroscopy (35 out of 40 cases), with an angled subcostal approach to the subphrenic space in over 85% of the cases. Forty-three drainage catheters were inserted using the Seldinger method; 37 (86%) had a size of 12 F or more, 21 were 16 F in size. Only two out of 43 catheters were double-lumen sump drains. The clinical condition improved after insertion of the catheter in all 37 patients. Definitive successful drainage, defined as hospital discharge without complementary surgery, was achieved in 32 patients (87%), without major complications. A temporizing effect was obtained in three additional patients (8%) who underwent curative surgery for the underlying process after complete drainage of the abscess. Two patients died from multiple organ failure before their abscess healed. Considerations for successful drainage of subphrenic abscesses include a good knowledge of the subphrenic space anatomy, the use of large-bore drainage catheters and the recognition and correct management of underlying enteric, biliary or pancreatic fistulas. PMID- 2924094 TI - Experiences at the new magnetic resonance imaging centre at Bristol. AB - The magnetic resonance imaging unit in Bristol has been housed in a new purpose built centre, shared between three District Health Authorities, but operated entirely separate from the National Health Service. Inasmuch as this is thought to be a unique arrangement, the publication of its finances and statistics have been readily tabulated at the end of its first year's operation, and may be of interest to others planning a similar organization. PMID- 2924095 TI - Radical radiotherapy for carcinoma of the vulva. AB - A study was made of 58 patients with carcinoma of the vulva treated by radical radiotherapy between 1965 and 1982. The choice of treatment technique was influenced by site and extent of disease as well as the general condition of the patient. The crude 5-year survival was 26% (15/58). Local control was achieved in 40% of cases and was associated with tumour size of 4 cm or less. Radionecrosis occurred in nine cases but none of these required surgical intervention. Surgery remains the treatment of choice for carcinoma of the vulva. This report emphasizes that radical radiotherapy has a curative potential in those cases considered unsuitable for surgery and that the necrosis type and rate are within the limits of acceptable morbidity. PMID- 2924096 TI - Films, screens and cassettes for mammography. AB - Various film-screen combinations intended for mammography have been compared for image quality and for dose. Image quality was assessed as in an earlier paper, using a test object having details which are both realistic and quantitative. Relative doses required to give film densities of 1.0 were measured. The Kodak MinR-MinR combination was taken as a standard against which others were compared, and in general a lower dose was accompanied by poorer image quality. The Fuji NH film with Fuji Hi-Mammo screen was the sole exception, giving slightly better image quality at about half the dose required by the MinR combination. A number of cassettes were also compared with each other and with evacuated envelopes. The Dupont Cronex cassette and three carbon-fibre fronted cassettes all performed well in image quality. PMID- 2924098 TI - Sickle-shaped scapulae in a patient with the Pierre Robin syndrome. PMID- 2924097 TI - Unusual long bone changes in thalassaemia: findings on plain radiography and computed tomography. PMID- 2924099 TI - Autopsy assessment of the Gunther vena caval filter. PMID- 2924100 TI - Demonstration on computed tomography of tracheomalacia in tracheobronchomegaly (Mounier-Kuhn syndrome). PMID- 2924101 TI - Lipoma arborescens of the knee. PMID- 2924102 TI - Radiation dose to urological surgeons during X-ray fluoroscopy for percutaneous stone extraction. PMID- 2924104 TI - Variation of image quality with X-ray tube potential in mammography. PMID- 2924103 TI - Intraoperative radioactive localization of an osteoid osteoma: a useful variation in technique. PMID- 2924105 TI - Aid to localization for computed tomographic biopsy and aspiration procedures. PMID- 2924106 TI - Ultrastructural localization of phenylethanolamine N-methyltransferase-like immunoreactivity in the rat locus coeruleus. AB - Adrenergic afferents from the rostral ventrolateral medulla are known to modulate the activity of noradrenergic neurons of the locus coeruleus (LC). The light and electron microscopic localization of a polyclonal antiserum directed against the adrenaline synthesizing enzyme, phenylethanolamine N-methyltransferase (PNMT) was used to determine the identity and targets of the adrenergic afferents to the LC of the rat brain. By light microscopy, varicose processes showing intense PNMT like immunoreactivity (LI) were seen throughout the neuropil surrounding neuronal perikarya which in adjacent sections were shown to contain immunoreactivity for the noradrenaline synthesizing enzyme, dopamine-beta-hydroxylase. Electron microscopy confirmed that these labeled varicose processes were primarily axon terminals. Terminals containing PNMT-LI constituted 30% (141 out of 464) of all identifiable terminals within the LC. These terminals were 0.5-1.8 micron in diameter and contained many small, clear and from 2 to 10 larger dense-core vesicles. The targets of the terminals with PNMT-LI were principally unlabeled (i.e. non-PNMT-containing) perikarya and dendrites. The synaptic junctions on perikarya were rare and exclusively symmetric; whereas, those on proximal (large) dendrites were somewhat more numerous and included symmetric as well as asymmetric membrane specializations. However, the vast majority (85% from a total of 141) of the terminals with PNMT-LI formed asymmetric synaptic junctions on unlabeled distal (small) dendrites and dendritic spines. In rare instances, the PNMT-immunoreactive terminals also formed synaptic junctions with other similarly labeled terminals. These findings provide the first ultrastructural evidence that adrenergic terminals in the LC (1) are one of the more prevalent synaptic inputs to the principally noradrenergic neurons; (2) have both symmetric and asymmetric synaptic specializations conventionally associated with inhibition and excitation, respectively; and (3) may modulate other adrenergic terminals through presynaptic mechanisms. In addition to the varicose processes, light microscopy revealed diffuse PNMT-LI throughout the LC. The ultrastructural correlate of this labeling was seen as patches of peroxidase product within the cytoplasm of a few perikarya and dendrites and throughout the cytoplasm of astrocytes identified by their discrete bundles of microfilaments. The detection of PNMT-LI in cells that are not known to synthesize adrenaline is surprising and suggests either a functional diversity for PNMT or amino acid sequence homologies with related enzymes which are enriched in the LC. PMID- 2924107 TI - Long-lasting reduction of dentate paired-pulse depression following LTP-inducing tetanic stimulations of perforant path. AB - Effects of high-frequency stimulations of the perforant path on the dentate paired-pulse depression were examined in urethane-anesthetized rats. The tetanic stimulations produced a long-term potentiation (LTP) of the excitatory synaptic transmission at the perforant path-dentate granule cell synapses in almost all animals examined. The strength of the early paired-pulse depression at an inter pulse interval (IPI) of 20 ms decreased significantly for at least 60 min after the tetanic stimulations, whereas the late paired-pulse depression at an IPI of 2 s remained almost unchanged. The reduction of the early paired-pulse depression was stepwise augmented by each of successive tetanic stimulations given at an interval of 10 min. A preceding antidromic stimulation of the mossy fibers depressed the population spike amplitude of perforant path response at an interval of 5-9 ms. The strength of the antidromic depression of population spike also decreased following the perforant path tetanic stimulations. These results suggest that tetanic stimulations of the perforant path produce a long-lasting reduction of the GABAergic recurrent inhibition in the dentate area associated with LTP. The possible mechanisms of the decrease in GABAergic inhibition produced by tetanic stimulations and its possible effects on the development of LTP with succeeding tetanic stimulations were discussed. PMID- 2924108 TI - Effect of serotonin on blood flow to the choroid plexus. AB - The choroid plexus contains a very high density of serotonin receptors and serotonin has been reported to influence the rate of formation of cerebrospinal fluid. The goal of this study was to examine effects of serotonin (5 hydroxytryptamine) on blood flow to the choroid plexus. Blood flow to the choroid plexus was measured in anesthetized cynomolgus monkeys and dogs using radioactive microspheres. Under control conditions, blood flow to choroid plexus was approximately 4 times greater than blood flow to the cerebrum in monkeys and approximately 7 times greater than blood flow to the cerebrum in dogs. Infusion of serotonin (40 micrograms.kg-1.min-1) into the left atrium increased blood flow to choroid plexus by 101 +/- 26% (mean +/- S.E.M.) in monkeys and by 201 +/- 45% in dogs. Serotonin did not affect cerebral blood flow. These findings suggest that serotonin may play an important role in regulation of blood flow to the choroid plexus. PMID- 2924109 TI - Repeated calcitonin treatment reduces the stimulation of inositol phospholipid by norepinephrine and serotonin in rat hippocampus and cerebral cortex. AB - Stimulation of inositol phospholipid hydrolysis by norepinephrine or 5 hydroxytryptamine was reduced in hippocampal or cortical slices from rats repeatedly injected with (Asu1.7)eel-calcitonin (2.5 IU/kg i.p.). This effect was specific, as the basal or carbamylcholine-stimulated inositol phospholipid hydrolysis was unchanged in slices from calcitonin-injected animals. The reduced responsiveness to norepinephrine did not reflect a decreased number or affinity of alpha 1-adrenergic recognition sites, suggesting that calcitonin treatment leads to a reduced coupling between alpha 1-adrenoceptors and phospholipase C. PMID- 2924110 TI - Distinct localization of prostaglandin D2, E2 and F2 alpha binding sites in monkey brain. AB - Autoradiographic localization of binding sites for [3H]prostaglandin D2, E2 and F2 alpha in the monkey brain was investigated by using in vitro labeling and an image processing system. Specific binding sites were distinctly localized in various nuclei in the hypothalamus, thalamus, and limbic system and their localization well correlated to the known functions of PGs in the brain by pharmacological and neurophysiological experiments. Furthermore, no direct relation was observed between the localization of PG binding sites and that of muscarinic cholinergic, alpha 1-adrenergic, and mu-opioid receptors in the preoptic area and hypothalamus. PMID- 2924111 TI - Satiety and sleep: the effects of bombesin. AB - Our recently proposed ischymetric hypothesis of the control of feeding and sleep predicts that both of these phenomena must be closely related. Whether food was available or not, peripherally administered bombesin produced an enhancement of total sleep by specifically increasing the duration of slow wave sleep but not the duration of paradoxical sleep. In all experimental situations, paradoxical sleep latency was increased. The data suggest an active role for endogenous bombesin-like peptides in the regulation of satiety and sleep. PMID- 2924112 TI - Developmental and hormonal factors in the sexually dimorphic, asymmetrical response to focal cortical lesions. AB - The developmental and hormonal determinants of the lateralized response to focal cortical suction lesions were examined in a series of experiments. In an initial study, Sprague-Dawley male rats 25, 30, 55 or 90 days of age, received right unilateral focal frontocortical suction lesions. Only 90-day-old rats developed hyperactivity, suggesting a specific role for maturational factors in the production of this response. Prepubertally castrated adult male rats receiving right frontocortical suction lesions at 90 days also failed to develop hyperactivity, suggesting that sexual maturational factors and/or the presence of testosterone are necessary for the expression of this response. Testosterone implants, producing physiological relevant levels of circulating testosterone reinstated the hyperactivity response to adult cortical lesions in prepubertally castrated male rats. Similar lesions in the left hemisphere, however, did not produce hyperactivity in castrated male rats with testosterone replacement. Finally, in ovariectomized adult female rats, testosterone did not allow the expression of a hyperactivity response to right frontocortical suction lesions. Together, these results demonstrate both an organizational and permissive role for sex steroids in the sexually dimorphic asymmetrical response to cortical injury. PMID- 2924113 TI - Antisera to the ganglioside GM1 do not have anti-myelin or anti-axon activities in vitro. AB - Four antisera to the ganglioside GM1 were tested for effects on myelin and axons when applied to mouse spinal cord-dorsal root ganglia explant cultures. None of the antisera to GM1 caused myelination inhibition or demyelination, while an antiserum to galactocerebroside caused both. Antisera to GM1 did not inhibit axonal outgrowth or destroy mature outgrowth zone axons, while an antiserum to a rat brain axolemma-enriched fraction did both. These results suggest that antibodies to GM1 do not have significant anti-myelin or anti-axon activity. PMID- 2924114 TI - Administration of L-2-oxothiazolidine-4-carboxylate increases glutathione levels in rat brain. AB - Sterile L-2-oxothiazolidine-4-carboxylate, given as a neutral 100 mmol solution at a dose of 8 mmol/kg subcutaneously, caused an increase in total glutathione concentration in the brain of treated rats. This finding could be important in understanding the role of glutathione in the central nervous system. PMID- 2924115 TI - Raphe cells grafted into the hippocampus can ameliorate spatial memory deficits in rats with combined serotonergic/cholinergic deficiencies. AB - The ability of embryonic raphe cells grafted into the hippocampus to restore spatial learning ability was tested in rats with combined serotonergic/cholinergic deficits. Embryonic raphe cells (E14) were transplanted into the hippocampus of serotonin-depleted rats. Two to 3 months after transplantation, control, lesioned and grafted rats were tested in a spatial memory task (a water maze) with and without the addition of atropine. All 3 groups could negotiate the water maze equally well, in non-drug conditions. The injection of atropine caused a severe disruption of performance only in the serotonin depleted rats. The presence of an active serotonergic graft was examined in the intact rat hippocampus using the serotonin releasing drug fenfluramine (FFA). A pronounced depression of hippocampal EEG was observed in control and grafted but not in lesioned rats 15 min after the injection of FFA. These results suggest the involvement of serotonin in cognitive functions in the rat. Furthermore, it is suggested that an interaction between serotonergic and cholinergic neurotransmission occurs in the hippocampus. PMID- 2924116 TI - Alterations of muscarinic cholinergic receptors in the hippocampal formation of stressed rat: in vitro quantitative autoradiographic analysis. AB - Alterations in muscarinic cholinergic (mACh) binding sites in the hippocampal formation of rats after immobilization stress (IM-stress) lasting 0.5 or 3 h were quantitated using a computer-assisted image analysis system on autoradiograms following labeling of frozen sections with [3H]quinuclidinyl benzilate (QNB). The concentration of acetylcholine (ACh) in the rat hippocampus after IM-stress was also measured and showed no significant change compared to control. IM-stress for 0.5 h produced significant increases in the concentration of mACh binding sites in the whole hippocampal formation and in two subdivisions studied (CA1 plus CA2 and dentate gyrus); after 3 h of stress, the increase remained significant only in the dentate gyrus. These findings suggest that IM-stress induce a hypersensitivity of the septo-hippocampal cholinergic system and the 'up regulation' of postsynaptic mACh receptors is more lasting in the dentate gyrus than in the hippocampus as a whole. PMID- 2924117 TI - Neuronal loss in lumbar dorsal root ganglia after proximal compared to distal sciatic nerve resection: a quantitative study in the rat. AB - The effects of unilateral sciatic nerve resections at proximal (thigh) or distal (proximal calf) locations on L4-L6 dorsal root ganglion (DRG) neuronal numbers have been studied in adult rats. Proximal nerve resection gave rise to a mean DRG neuronal loss of 27%, whereas in distal lesions a mean cell loss of 7% was found. This difference in cell loss between proximal and distal sciatic nerve resections is highly significant (P less than 0.001). PMID- 2924119 TI - Observations on static and dynamic responses of muscle stretch receptors in kittens. AB - In 5-19-day-old kittens anesthetized with Saffan, the discharges of de-efferented triceps surae muscle receptors were recorded from afferent fibers in dorsal root filaments. The conduction velocities of the afferent fibers ranged between 7 and 30 m/s. Receptors were identified as spindles on the basis of their response to muscle stretch and, whenever possible, the pause in their discharge during muscle contraction. Spindles responding with sustained discharges to muscle extensions of less than 1 mm could be found in 5-8-day-old kittens, provided the muscles was left 'in situ', with intact skin, tendon and aponeuroses. However, such responses were rare before 10 days, and the majority of receptors essentially displayed phasic responses to muscle stretch, in agreement with previous observations. In responses to sinusoidal muscle stretching of 0.1-0.5-mm amplitude, kitten receptors were easily driven to discharge one impulse per cycle at frequencies of 10-15 Hz. But unlike adult spindles, they could not follow higher frequencies unless the amplitude of stretch was increased. The maturation of dynamic responses is slower than that of static responses in kitten spindles. In the first postnatal weeks, small changes in muscle length are poorly signaled to the central nervous system. PMID- 2924118 TI - GM1 ganglioside attenuates the behavioral deficits but not the granule cell damage produced by intradentate colchicine. AB - Bilateral injection of 3.5 micrograms of colchicine into the dentate gyrus produced hyperactivity, impaired retention of a passive avoidance task, and enhanced the motor stimulant effects of a dopaminergic agonist (apomorphine) and the analgesic effects of morphine. In contrast, there was no alteration in scopolamine-induced hyperactivity. These effects were associated with a decrease in the thickness of the granule cell layer in both the superior and inferior blade of the dentate gyrus and a coincident decrease in the size of the overlying dentate molecular layer. Intraperitoneal injection of monosialoganglioside GM1 (30 mg/kg) beginning 3 days prior to surgery and continuing for 25 days following surgery appeared to limit the extent and duration of these behavioral effects. GM1 facilitated recovery of motor activity and attenuated the impaired retention of the passive avoidance task and the alterations in pharmacological sensitivity following intradentate injection of colchicine. Despite the facilitative effects of GM1 on behavior histological analysis of the hippocampus did not reveal a protective effect of this compound on colchicine-induced granule cell destruction. The results of these studies suggest that intradentate injection of colchicine is a useful model of human diseases where only restricted populations of neurons are damaged. Furthermore, these studies indicate that the use of monosialoganglioside GM1 might be a useful primary or adjunct approach to the treatment of neurodegenerative disorders and their behavioral sequelae. PMID- 2924120 TI - Ontogenesis of chromogranin A and B and catecholamines in rat adrenal medulla. AB - The ontogenesis of chromogranins A and B and catecholamines was investigated for rat adrenal medulla. The chromogranins, the major secretory peptides of chromaffin granules, were characterized by one- and two-dimensional immunoblotting. Chromogranin B appeared identical in fetal and postnatal adrenals. On the other hand a significant portion of chromogranin A immunoreactivity in fetal adrenals was present in a component which was identified as a proteoglycan form of chromogranin A. In adult adrenals this proteoglycan chromogranin A was different and much less prominent. Total chromogranins and catecholamines increased parallely from the 17th prenatal day to the adult stage. However in early periods of development chromaffin granules are likely to contain relatively higher catecholamine levels than adult granules. At the end of the gestational period both the ratio of adrenaline to noradrenaline and of chromogranin A vs B increases sharply. These results establish that from the 17th prenatal day onward fetal adrenal glands contain chromaffin granules which are filled with both the major secretory peptides and catecholamines. The relative composition of the secretory content (adrenaline vs noradrenaline and chromogranin A vs chromogranin B) changes at the end of the gestational period in parallel with the development of the corticosteroid producing adrenal cortex. PMID- 2924121 TI - Bombesin microinfusion into the rat hypothalamic paraventricular nucleus increases blood glucose, free fatty acids and corticosterone. AB - Bombesin is a particularly potent hyperglycemic agent when administered intraventricularly or intracisternally in the rat. Because bombesin-like immunoreactivity is found in several forebrain regions implicated in glucoregulation, the ability of direct hypothalamic microinfusions of this peptide to affect serum metabolic fuel levels was tested. Three experiments, using anesthetized, acutely infused rats, or unanesthetized rats with chronic intracranial implants, showed that microinfusion of bombesin into the hypothalamic paraventricular nucleus caused significant, dose-related increases in serum glucose; infusions into the lateral hypothalamus or the caudate nucleus were ineffective. Infusions into the ventromedial nucleus significantly elevated glucose only in acutely anesthetized rats. In unanesthetized rats with chronic intracranial cannulae, bombesin infusions into all 3 hypothalamic sites, but not the caudate-putamen, significantly elevated blood free fatty acids, while only infusions into the paraventricular nucleus caused significant dose-related increases in blood corticosterone. The results demonstrate that the paraventricular nucleus is a sensitive site for bombesin-induced elevation of blood glucose, free fatty acids, and corticosterone. They also imply that the bombesin binding sites and immunoreactive terminals previously identified in these regions may be involved in the central regulation of circulating metabolic fuel levels and the pituitary-adrenal axis, and that the effects of acute surgery may augment the hyperglycemic response to intrahypothalamic bombesin administration. PMID- 2924122 TI - Sex difference in the visual projections of young chicks: a quantitative study of the thalamofugal pathway. AB - We investigated quantitatively the thalamo-hyperstriatal visual projections of chickens by injecting the fluorescent dye True blue (TB) in either side of the Wulst on day 2 post hatching. The ratios resulting from the comparison of the number of cells retrogradely labelled in the nuclei dorsolateralis anterior thalami (DLA) contralateral and ipsilateral to the site of injection (C/I ratios) revealed a structural asymmetry in the thalamofugal projections of male chicks (n = 17) but not in those of females (n = 12). In the males, TB injections in the right hyperstriatum resulted in higher C/I ratios (37 +/- 14%) compared to injections in the left hyperstriatum (22 +/- 7%). Thus, the left DLA (fed by the right eye) was found to give rise to a more developed visual projection compared to the right DLA (fed by the left eye). No such difference was found in female chicks (41 +/- 13% and 38 +/- 12%, respectively): each DLA gives rise to similarly developed visual projections. We also report evidence of higher densities of cell bodies labelled in the DLA of females compared to males. These results are discussed in the light of experiments demonstrating sex differences in functional asymmetry in chicks tested with the left or right eye occluded. PMID- 2924123 TI - Stimulation of choline acetyltransferase activity by retinoic acid and sodium butyrate in a cultured human neuroblastoma. AB - Choline acetyltransferase (Acetyl-CoA:choline O-acetyltransferase, EC 2.3.1.6, abbreviated ChAT), the biosynthetic enzyme for acetylcholine and acetylcholinesterase (EC 3.1.1.7, abbreviated AChE) are expressed in a human cholinergic neuroblastoma cell line, MC-IXC. We have shown that ChAT activity can be regulated in culture by retinoic acid, an active metabolite of vitamin A, and by sodium butyrate, an organic fatty acid. Optimal concentrations of these agents produce 4.3-fold and 1.6-fold increases in ChAT activity, respectively. The effects of retinoic acid are statistically significant after 24 h, whereas for sodium butyrate significant differences are seen only after 48 h. Since retinoic acid stimulation of ChAT activity was reversed only by trypsin treatment and not by removal of retinoic acid from the medium, this suggests that this agent may be acting at the level of the cell surface. Other differentiating conditions, such as culture in serum-free medium or addition of 1-2% dimethylsulfoxide did not increase ChAT activity. Acetylcholinesterase activity was shown to increase only in the presence of sodium butyrate, suggesting that retinoic acid and sodium butyrate may be acting via different pathways. Retinoic acid and sodium butyrate both seem to be permissive rather than instructive in regulating ChAT activity in that they are unable to induce ChAT expression de novo in cell lines which do not already express ChAT activity. PMID- 2924124 TI - Mechanism of activation of choline acetyltransferase in a human neuroblastoma cell line. AB - In our previous report we have shown that the enzyme choline acetyltransferase (ChAT), responsible for the synthesis of the neurotransmitter acetylcholine, can be regulated in response to treatment by either retinoic acid or sodium butyrate. These responses were dose and time dependent, but the mechanism by which these agents were acting was not understood. We now report the results of studies aimed at elucidating the level at which both sodium butyrate and retinoic acid are able to increase ChAT activity. The effects of these agents on macromolecular synthesis appeared to be limited to small but statistically significant increases in the rate of RNA synthesis. However, inhibition of DNA, RNA and protein synthesis in these cells had no effect on the stimulation of ChAT activity by either sodium butyrate or retinoic acid. Several experiments appeared to rule out a role for cyclic AMP or protein kinase C in the regulation of ChAT activity, even though retinoic acid treatment could increase endogenous levels of cyclic AMP 3- to 4-fold over the time course of ChAT activity stimulation. Experiments performed to determine kinetic parameters of this enzyme demonstrated changes only in the Vmax, but not the Km of ChAT, suggesting that the affinity of enzyme for either of its substrates was not responsible for the increase in specific activity. Taken together, this evidence suggests that the activation of choline acetyltransferase in this human neuroblastoma cell line occurs at the post translational level. PMID- 2924126 TI - Neuropeptide Y-containing neurons in the human infant hippocampus. AB - Using immunohistochemistry, high concentrations and widespread distribution of neuropeptide Y-immunoreactive (NPY-IR) neurons were found and examined in each region of the hippocampal formation from birth to 42 years. NPY interneurons are particularly numerous in the stratum oriens of the CA1 subfield, in the deep layers of the subicular complex and entorhinal cortex. They are multipolar round, ovoid or triangular or bipolar and fusiform. There is a dense network of NPY-IR nerve fibers in the subicular complex and the entorhinal cortex. In addition, numerous NPY-IR nerve cell bodies and fibers are observed in the angular bundle and the adjacent white matter and this contrasts with the absence of NPY immunoreactivity in the fiber tracts of the alveus. These NPY-IR neurons which correspond to the interstitial neurons of the white matter, have the morphology and the size of the interneurons detected in the cortex. During the postnatal brain growth spurt which corresponds to the phase of rapid myelination, there is no decline in total number of NPY-IR neurons but there is a decrease in density. They have been spread apart by the growth of the rest of the tissue. So in humans, the total number of NPY nerve cell bodies in the hippocampal system, firmly established at birth, is not modified during consequent brain growth which continues until ages 3-4 years and stays stable at least until age 42 years. PMID- 2924125 TI - Enhanced phosphoinositol hydrolysis in response to vasopressin in the septum of the homozygous Brattleboro rat. AB - Arginine8-vasopressin (AVP) receptors in the septum of the Long-Evans rat have been shown to be both pharmacologically (displacement profiles) and functionally (ability to stimulate phosphoinositide hydrolysis) similar to the peripheral V1 type receptor for AVP. Previous binding studies of AVP receptors in the septum of heterozygous (HE) and homozygous (vasopressin-deficient, HO) Brattleboro (BB) rats revealed an increased number of receptors with a lower affinity for AVP in the HO-BB rat when compared to the HE-BB rat. To determine the effect of these receptor changes in the HO-BB rat septum on the postreceptor response of the tissue to AVP, concentration-response relationships for AVP-stimulated phosphoinositide hydrolysis were examined in septal slices from age-matched, adult male HE- and HO-BB rats. AVP-stimulated accumulation of [3H]inositol-1 phosphate (IP1) was significantly greater in the HO-BB (43.7%) than in the HE-BB (13.7%) at AVP concentrations of 10(-08) to 10(-05) M. The two groups did not, however, differ in their ability to stimulate [3H]IP1 accumulation in response to 2.0 mM carbachol. When the AVP-stimulated phosphoinositide response in both genotypes was compared to that obtained for the Long-Evans (LE) rat (the parent strain of the Brattleboro rat) septum under the same assay condition, it was found that the response in the HE-BB was much lower than in the LE. AVP receptor binding capacity (Bmax) correlated (r = 0.975) with release of IP1 ([3H]IP1 accumulation) for all 3 groups studied (LE, HE, HO).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2924127 TI - Angiotensin II-induced rhythmic jaw movements in the ketamine-anesthetized guinea pig. AB - The EMG activity of the left anterior digastric muscle as well as associated jaw movements were studied in ketamine-anesthetized guinea pigs that had received i.v. infusions of angiotensin II (ANG-II). Rhythmic jaw movements with two distinct movement profiles were associated with ANG-II infusion. One movement profile was typified by vertical jaw opening and closing movements with little or no associated horizontal movement. The second rhythmical jaw movement profile was unlike the first in that jaw closing was accompanied by a significant horizontal deflection of the jaw. Both jaw movement profiles were similar in that little or no horizontal movement occurred during jaw opening. Tongue protrusions were also observed during jaw opening in both cases. The results show that ANG-II induces rhythmic jaw movements in anesthetized guinea pigs. ANG-II-induced jaw movement profiles and digastric muscle EMG activity are similar to those seen after an i.v. injection of apomorphine in the anesthetized guinea pig, and to those associated with lapping in the awake animal. PMID- 2924128 TI - Extracellular increase of hypoxanthine and xanthine in the cortex and basal ganglia of fetal lambs during hypoxia-ischemia. AB - A microdialysis procedure was used to sample purine catabolites from the extracellular compartment of two areas of the fetal brain, the cerebral cortex and the striatum region. Seven exteriorized, anesthetized fetal sheep were studied during conditions of normal oxygenation and during asphyxia induced by stepwise lowering of maternal placental perfusion pressure. Fetal cerebral blood flow (CBF) was measured with the 133Xe washout method. Somatosensory evoked potentials were recorded during tactile stimulation of the fetal snout. The purine catabolites hypoxanthine (HX), xanthine (Xan), guanosine (Gua), inosine (Ino) and adenosine (Ade) were measured in arterial and venous plasma and in the dialysate by a HPLC method. During gradually increasing asphyxia HX increased 4-6 fold both in cerebral tissue and in arterial plasma, while Xan rose 1.5-3 times in cerebral tissue and arterial plasma. Gua did not change in either tissue or blood and Ino did not rise until at the most extreme degree of asphyxia it rose 2 4-fold. Ade concentrations remained unaltered during moderate asphyxia (when CBF rose 3-fold), but demonstrated a significant (2-3-fold) augmentation at the most extreme degrees of asphyxia. The results thus suggests a significant accumulation of oxypurines, especially HX, in the interstitium of the fetal brain during asphyxia. The rise in xanthine concentration demonstrates the presence of an activity of xanthine oxidase in brain tissue. A discrepancy between the elevation of CBF and of the tissue concentration of Ade does not support a direct role of Ade in the asphyctic cerebral vasodilation in the fetus. PMID- 2924129 TI - Impaired up-regulation of type II corticosteroid receptors in hippocampus of aged rats. AB - Several recent investigations have reported a decline of rat hippocampal corticosteroid-binding receptors (CSRs) with aging. This decline has been proposed to be an initial cause (through disinhibition) of the elevated adrenal steroid secretion that apparently occurs with aging; however, it could instead be an effect of corticoid elevation (through down-regulation). In order to assess the effects of age on CSR biosynthetic capacity in the absence of down-regulatory influences of endogenous corticoids, as well as to study aging changes in CSR plasticity, we examined the up-regulation of hippocampal CSR that follows adrenalectomy (ADX). The rat hippocampus contains at least two types of CSR binding and differential analysis of types I and II CSR was accomplished by selective displacement of [3H]corticosterone with RU-28362, a specific type II agonist. In young (3 months old) Fischer-344 rat hippocampus, up-regulation of type II binding above 2-day ADX baseline was present by 3-7 days and increased still further by 8-10 days post-ADX; type I CSR density did not change significantly between 1 and 10 days post-ADX. However, in aged (24-26 months old) rats, type II CSR up-regulation did not occur over the 10 day post-ADX period. Thus, the age-related impairment of type II up-regulation may reflect an intrinsic deficit in CSR biosynthesis or lability that is independent of the acute endogenous adrenal steroid environment. PMID- 2924130 TI - Modulations of EEG activity in the entorhinal cortex and forebrain olfactory areas during odour sampling. AB - With the aim of determining a possible role of the entorhinal cortex (EC) in the processing of olfactory information, its electrical activity was recorded during different types of odour sampling behaviour. The EC spontaneous field potentials (EEGs) were related to those recorded simultaneously from the more rostrally lying olfactory bulb (OB) and prepiriform cortex (PPC), using coherence functions. The coherence values are measures of coupling between two neuronal populations. Auto- and coherence spectra were characterized by a peak in the beta band (35-36 Hz) and another in the 16-20 Hz band. For the beta-peak of the PPC-EC coherence it was shown that both the maximal values and the median frequency decrease during the first 0.5-1.0 s of a trial in a two-choice odour discrimination task. These transients differed significantly for CS+ and CS- trials. However, no such difference was observed during exploratory sniffing at the same pair of odorants. It was concluded that during sniffing the degree of coupling of the EC with the PPC depends on the behavioural context but not on the quality of the odorants. As regards the 16-20 Hz components it was shown, using bispectral analysis, that these components represent the 1/2 subharmonic of the beta-components. The subharmonic components were enhanced during the initiation of sniffing. This means that the neural networks of OB, PPC and EC have non linear dynamic properties. These networks show different modes of oscillatory behaviour, characteristic of the restful state and of the active sniffing state. Theoretical implications of these experimental results are discussed. In conclusion, it was demonstrated that modulations with sniffing behaviour are present in the beta-EEG components and their subharmonics in the olfactory brain areas including the EC. This indicates that the latter is involved in processes of the evaluation of olfactory cues in relation to the animal's behaviour. PMID- 2924131 TI - Evidence for the involvement of a descending cholinergic pathway in systemic morphine analgesia. AB - The analgesic effect of morphine sulfate (3-5 mg/kg, i.p.) was assessed by both tail-flick and hot-plate tests in unanesthetized restrained rats. Intrathecal administration of atropine sulfate (10 micrograms) in the lumbar region of the spinal cord powerfully reduced the analgesia induced by systemic administration of morphine. This action did not result from the diffusion of atropine from its administration site to more rostral sites in the central nervous system. In spinal rats, atropine failed to reverse morphine analgesia, thus strongly suggesting that either a cholinergic descending pathway or a spinal local cholinergic circuit activated by an unknown descending pathway may be involved in the systemic morphine analgesia. In addition, the involvement of the alpha adrenergic descending pathway in morphine analgesia is confirmed, whereas that of the serotonergic descending pathway is less prominent. PMID- 2924132 TI - Electrophysiological evidence for axonal branching of ambiguous laryngeal motoneurons. AB - Laryngeal motoneurons in the nucleus ambiguous (NA) were identified antidromically by stimulation of the ipsilateral superior laryngeal nerve (S) and/or the recurrent laryngeal nerve (R). In some NA motoneurons, antidromic spikes elicited by both S and R stimulation collided with the spontaneously occurring discharges. In the same neuron, spikes evoked antidromically by stimulation of one laryngeal nerve always collided with antidromic spikes elicited by stimulation of the other laryngeal nerve. Of 105 NA neurons activated by S and R stimulation, 36 neurons satisfied the criteria, and were classified as NA neurons with branching axons (branching NA (B-NA) neurons). Those neurons activated by either S or R stimulation but not both were classified as NA neurons without branching axons (unbranched NA (UB-NA) neurons). Mean antidromic latencies of B-NA neurons were 0.79 +/- 0.20 ms to S stimulation and 1.91 +/- 0.45 ms to R stimulation and those values for UB-NA neurons were 0.84 +/- 0.17 ms to S stimulation and 2.10 +/- 0.53 ms to R stimulation respectively. None of these mean values were significantly different from one another. Conduction time in the unbranched portion of the branching axon was estimated according to the equation reported by Anderson and Yoshida. The mean conduction time for 20 B-NA neurons was 0.45 +/- 0.35 ms. The branching point in B-NA neurons was estimated on the basis of the conduction time in the unbranched stem portion and those times in two branches of a branching axon measured electrophysiologically. The results suggest that the majority of B-NA neurons bifurcate within a half axonal length.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2924133 TI - Synaptic organization of the pedunculopontine tegmental nucleus of the cat. AB - The synaptic organization of the feline pedunculopontine tegmental nucleus (PPN) was studied electron microscopically. The bouton covering ratios were calculated in various sizes of PPN neurons, and the ratios of large neurons (56%) were found to be much higher than those of small neurons (16%). The PPN neuron dendrites usually showed some varicosities, and spines were observed on both somatic and dendritic profiles. Among a total of 1021 synapses sampled at random, axosomatic, axodendritic and axospinous synapses comprised 21.7, 61.2 and 14.1%, respectively. On the basis of the postsynaptic junction, these synapses were classified into the symmetric (66.3%) and the asymmetric (33.7%) types. The percentage of symmetric synapses was much higher on the soma (91.0%), and the large (69.4%) and medium-sized (63.2%) dendrite, while that of asymmetric synapses showed a higher value on the small dendrite (55.5%) and the dendritic spine (50.8%). Axoaxonic, dendrodendritic and dendroaxonic synapses, although not so frequent, were, in part, involved in the serial synapse or the synaptic triad. It is concluded that some PPN neurons are spiny, and that axosomatic, axodendritic and axospinous synapses are the main synaptic constituents and besides those synapses a more complex synaptic organization exists in this nucleus. PMID- 2924134 TI - Nicotine infused into the nucleus accumbens increases synaptic dopamine as measured by in vivo microdialysis. AB - It has been postulated that addiction to nicotine is mediated by dopamine release in the mesolimbic system. It is possible that nicotine might act directly on the dopamine terminals to release dopamine. This hypothesis was tested by infusing nicotine through a microdialysis probe into the nucleus accumbens of freely moving rats. Dopamine, dihydroxyphenylacetic acid, and homovanillic acid from the extracellular space were collected by microdialysis and measured by high pressure liquid chromatography. Nicotine increased extracellular dopamine in a dose related manner. Systemic injection of the nicotine antagonist mecamylamine blocked the dopamine increase induced by local nicotine. These results suggest that nicotine releases dopamine by a local action in the nucleus accumbens terminal area of the mesolimbic system. Presynaptic induction of dopamine release might play a role in nicotine addiction. PMID- 2924135 TI - Fetal brain grafts induce recovery of learning deficits and connectivity in rats with gustatory neocortex lesion. AB - Three groups of rats showing disrupted taste aversion due to gustatory neocortex lesions, were studied. One group received a transplant of homotopic cortical tissue, another of heterotopic tectal tissue, obtained from 17-day-old fetuses. The third group remained without transplant as a lesioned control group. Comparisons of the taste aversion scores before and after graft, revealed that cortical grafted animals significantly improved the taste aversion, whereas those which received tectal grafts, and the cortical-lesioned controls did not. Moreover, results with horseradish peroxidase (HRP) histochemistry revealed that the homotopic, but not the heterotopic, brain transplants were able to re establish connections with amygdala and with the ventromedial nucleus of the thalamus areas who normally kept connectivity with the gustatory neocortex. These results support the hypothesis that fetal brain transplants can reestablish cognitive functions, as well as connectivity with its host tissue. PMID- 2924136 TI - GABAergic septohippocampal neurons contain parvalbumin. AB - Septal axons were visualized in the hippocampus by anterograde transport of Phaseolus vulgaris leucoagglutinin (PHAL) injected into the medial septal region, which contains large numbers of parvalbumin (PV)-immunoreactive somata. A proportion of the PHAL-labelled afferents in the hippocampus were shown to be immunoreactive for PV by immunostaining alternate sections. This population of septohippocampal axons alone was found to be immunoreactive for gamma aminobutyric acid (GABA) following post-embedding immunogold staining of ultrathin sections cut from the same material. PMID- 2924137 TI - Regional calcium accumulation and kainic acid (KA)-induced limbic seizure status in rats. AB - The sites of calcium accumulation were studied by 45Ca autoradiography during kainic acid (KA)-induced limbic seizure in rats. Two hours after KA injection into unilateral amygdala, calcium accumulated in CA3 of the hippocampus, lateral septal nucleus and thalamic reticular nucleus on KA-injected side. Those sites coincided with the sites where neuronal cell damage appeared 4 h after KA injection. These results suggested that regional calcium accumulation might be responsible for neuronal cell loss induced by seizures. PMID- 2924138 TI - Functional muscarinic supersensitivity in denervated rat hippocampus. AB - The effects of carbachol (CCh), a cholinergic agonist, were compared in voltage clamped hippocampal pyramidal neurons in vitro, obtained from normal and fimbria fornix-lesioned rats. A substantial increase in sensitivity to the effects of CCh was seen in denervated neurons. The supersensitivity was demonstrated on both the inward leak current and the calcium-dependent potassium current, IAHP. These findings provide convincing evidence for cholinergic denervation supersensitivity in the hippocampus. PMID- 2924139 TI - Depression of calcium current at mouse motor nerve endings by polycationic antibiotics. AB - The hypothesis according to which polycationic antibiotics produce neuromuscular block by interfering with the Ca current of motor nerve terminals has been examined using external electrodes in nerve-muscle preparations of the mouse. It was found that kanamycin, bekanamycin and polymyxin B depressed presynaptic Ca currents probably by neutralizing negative surface charges. PMID- 2924140 TI - Blocking of morphine-induced locomotor hyperactivity by amygdaloid lesions in C57BL/6 mice. AB - Bilateral lesions of the amygdaloid complex in C57BL/6 mice prevented the occurrence of morphine-induced hypermotility (running fit). This effect, that was different from that observed after hippocampal lesions but similar to that observed after caudate lesions, confirms the role of the basal ganglia catecholaminergic system in the development of the motor stimulation consecutive to the administration of this opiate receptor agonist. PMID- 2924141 TI - Photoresponses of an extraocular photoreceptor associated with a decrease in membrane conductance in an opisthobranch mollusc. AB - The photoresponse of an extraocular photoreceptor, the photoresponsive neuron (A P-1) in the abdominal ganglion of Onchidium verruculatum, was studied by using a voltage-clamp with two micropipettes and a monochromatic light. When the A-P-1 was voltage-clamped at resting membrane potential levels, light induced a slowly developing inward current which peaked at about 20 s. A decrease in membrane conductance accompanied this light-induced current which corresponded to the depolarizing photoreceptor potential in the unclamped A-P-1. The relationship between the peak of the current response and light intensity could be predicted by using the modified Michaelis-Menten equation. The spectral sensitivity for the photoresponse had a peak at 490 nm. The steady-state light-induced current was a non-linear function of the membrane potential. The current-voltage relationship for the instantaneous light-induced current was almost linear. In normal (10 mM K+) saline, the polarity of the instantaneous light current reversed from inward to outward at about -67 mV, and doubling the external K+ from 10 to 20 mM shifted the reversal potential to about-50 mV, similar to that predicted by a K+ electrode. These results suggest that the light-induced current or the depolarizing receptor potential of A-P-1 is due to the light suppression of a voltage- and time-dependent K+ current. PMID- 2924142 TI - Pretectal and tectal projections to the homologue of the dorsal lateral geniculate nucleus in the pigeon: an anterograde and retrograde tracing study with cholera toxin conjugated to horseradish peroxidase. AB - The possibility of a projection from the pretectal nucleus, lentiformis mesencephali (LM), to the principal optic nuclei (OPT) of the dorsolateral thalamus was investigated using cholera toxin conjugated to horseradish peroxidase (CT-HRP). Injections of CT-HRP into LM produced massive anterograde labeling of the pars lateralis of the nucleus dorsolateralis anterior thalami (DLL), and sparse labeling of the pars magnocellularis (DLAmc). Injections of CT HRP into OPT in turn produced massive retrograde labeling of both parvocellular and magnocellular divisions of LM. These results relate to possible neural mechanisms underlying optokinetic nystagmus. OPT injections also retrogradely labeled small neurons throughout the rostrocaudal extent of the tectum which were confined to superficial laminae. PMID- 2924143 TI - Subjective pain sensation is linearly correlated with the flexion reflex in man. AB - In an attempt to define the relationship between physiological and psychological correlates of pain during low-level voluntary contraction, electrical stimuli between threshold and maximally tolerable intensities were delivered to the sole of the foot in 7 normal subjects. The two measures used to assess the response magnitude are: (1) the flexion reflex (FR) in the ipsilateral biceps femoris (BF), and (2) the estimate of perceived intensity reported on a visual analog scale (VAS). Our results showed that both BF FR area and VAS ratings bore a direct linear relationship with stimulus intensity and with each other, suggesting that at least under our paradigm, the sensory component of a nociceptive stimulus may already be largely set at the spinal interneuronal level. PMID- 2924144 TI - A preliminary description of the regeneration of optic nerve fibers in a reptile, Vipera aspis. AB - Crushing or freezing the optic nerve of the viper leads initially to the anterograde degeneration of the optic nerve fibers and to an extensive retrograde demyelination process associated with the degeneration of some retinal ganglion cells. By the 45th postoperative day, regenerating unmyelinated axons can be identified in the damaged region of the optic nerve. These fibers reach the chiasm and the marginal optic tract by the third postoperative month. The radioautographic tracing method shows that some nuclei of the primary visual system begin to be reinnervated by about the 5th postoperative month; this reinnervation was not, however, completely restored in those specimens with the longest postoperative survival of 220 days. PMID- 2924145 TI - Natural killer cell activity in vasopressin-deficient rats (Brattleboro strain). AB - Several lines of evidence suggest that the neuropeptide vasopressin is involved in the regulation of the immune system. We explored this possibility by comparing the cytotoxic activity of natural killer (NK) cells in Brattleboro (DI) rats, which are homozygous for diabetes insipidus and lack vasopressin, and Long-Evans (LE) rats, the strain from which DI rats were derived. Additionally, we compared the effects of swim stress, morphine administration and vasopressin replacement on NK cell activity in these two strains. In DI rats, NK cell activity, determined by a standard 4-h chromium-release assay, was significantly higher than in LE rats. Both swim stress and morphine administration suppressed NK activity in DI and LE rats. There was no difference in the level of suppression between the two strains. Vasopressin replacement normalized water intake in DI rats, but had no significant effect on NK cell activity. DI rats exhibited lower plasma corticosterone levels, which were not elevated by vasopressin replacement. The results suggest that the lack of vasopressin in DI rats elevates baseline NK cell activity, probably via mechanisms that are secondary to the vasopressin deficiency (e.g. lower corticosterone levels). Neither vasopressin nor other hormones affected by vasopressin deficiency seem to be involved in the acute modulating effects of stress and morphine on NK cells. PMID- 2924146 TI - Variations in the cellular incorporation of [3H]proline. AB - Injections of [3H]proline into various CNS nuclei in the cat and into the rat dorsal column nuclei labeled terminal targets of those regions despite the fact that only glia (and not neuronal somata) were labeled at the injection site. In contrast, although injections into cat CNS fiber tracts labeled glial cells surrounding the axons, neither the axoplasm, somata or terminals of those axons were labeled. In addition, injections into cat PNS dorsal root ganglia labeled ganglion cells. These results support previous findings suggesting that 3H proline is incorporated into a class of molecules in the CNS (but not PNS) that is transferred from glia into neuronal somata (but not axoplasm). PMID- 2924147 TI - Hypothalamic axons terminate on forebrain cholinergic neurons: an ultrastructural double-labeling study using PHA-L tracing and ChAT immunocytochemistry. AB - A correlated light and electron microscopic study combining choline acetyltransferase immunocytochemistry with anterograde tracing of Phaseolus vulgaris leucoagglutinin revealed that axons of lateral hypothalamic neurons terminate on forebrain cholinergic projection cells. This finding is discussed in relation to direct and indirect corticopetal systems. PMID- 2924148 TI - Inhibitory influences on hypoglossal neural activity by stimulation of midpontine dorsal tegmentum in decerebrate cat. AB - In the spontaneously breathing decerebrate cat, the properties of the suppressive effects on hypoglossal nerve activity and on diaphragmatic activity elicited by stimulation of the midpontine dorsal tegmentum (DTF area) were analyzed. Stimulation simultaneously decreased the activities of the hypoglossal nerve as well as that of the diaphragm. However, the inhibitory influences on the above two kinds of activities were different in nature. Diaphragmatic activity, once suppressed by stimulation, recovered and gradually became greater in amplitude in spite of the continuation of stimulation. In contrast, DTF stimulation depressed tonic discharges of the hypoglossal nerve, and the decreased tonic nerve activity persisted after stimulation ended. Rhythmic hypoglossal activity, once suppressed by stimulation, reappeared during DTF stimulation. Such a rhythmic activity, however, vanished after the termination of stimulation, although the rhythmic diaphragmatic activity did not. PMID- 2924149 TI - Direct electrical stimulation of the superior ovarian nerve in rats causes an increase in neuronal activity in the ipsilateral ovarian plexus nerve. AB - Ovarian blood flow and neuronal activity in the ovarian plexus nerve (OPN) were monitored before, during and after direct electrical stimulation of the central cut end of the ipsilateral superior ovarian nerve (SON). Blood flow did not change during the observation period. Stimulation of the SON increased the frequency of action potentials in the OPN, suggesting an ovarian reflex pathway mediated by the SON and the OPN. PMID- 2924150 TI - Exploration and habituation in Purkinje cell degeneration mutant mice. AB - Purkinje cell degeneration (pcd) mutant mice lose virtually all Purkinje cells. It was found that the pcd mutants did not show within-sessions habituation in terms of hole-poking responses. This type of perseverative responding has been found in rats with limbic system damage and implies a role for the cerebellum in behavioral inhibition. PMID- 2924151 TI - Kindling induced changes in parvalbumin immunoreactivity in rat hippocampus and its relation to long-term decrease in GABA-immunoreactivity. AB - The immunoreactivity of parvalbumin (PV), a Ca2+-binding protein present in a subpopulation of interneurons, was studied in the hippocampal CA1 region during kindling epileptogenesis, induced by tetanic stimulation of the Schaffer collateral/commissural fibers. PV-immunoreactivity was increased in comparison to controls after 13 afterdischarges and after the induction of generalized seizures. A quantification of the number of PV-immunoreactive somata showed an increase of 20% in both stages of kindling. This level had returned to baseline level 31 days after the last seizure. These results imply that changes in PV immunoreactivity are related to seizure activity rather than to the long-term increase in seizure sensitivity in kindled animals. Co-localization study in controls showed that 32% of PV-immunoreactive somata were also immunopositive for GABA. A colocalization study in stratum oriens and pyramidale on the stimulated side of kindled animals 31 days after the last generalized seizure showed neither a reduction in the number of PV-immunoreactive somata nor in the number of GABA immunopositive cell bodies that co-localized with PV. In contrast, the number of GABA-immunoreactive somata that did not co-localize with PV was reduced by 50%. It has been shown that a large influx of Ca2+ plays a crucial role in epileptogenesis. Here we demonstrate that the presence of the calcium-binding protein parvalbumin seems to exert a protective effect against the process that leads to a decrease in GABA content. PMID- 2924152 TI - Optic tract stimulation evokes GABAA but not GABAB IPSPs in the rat ventral lateral geniculate nucleus. AB - The inhibitory postsynaptic potentials (IPSPs) evoked in neurons of the rat ventral geniculate nucleus (vLGN) by electrical stimulation of the optic tract and the action of GABA and baclofen on the same cells were studied using intracellular recording technique in an in vitro slice preparation. A short latency short duration IPSP always followed the monosynaptic excitatory postsynaptic potential (EPSP). This IPSP reversed in polarity at about -65 mV and was reversibly blocked by bicuculline (50 microM) thus indicating that it represents a GABAA receptor-mediated IPSP. No long-lasting IPSP was evoked in vLGN cells by stimulation of the optic tract, while in the same slice, long lasting GABAB IPSPs were routinely recorded in the dorsal lateral geniculate nucleus. GABA applied by ionophoresis evoked a hyperpolarization that had a reversal potential close to -70 mV and was antagonized by bicuculline. Baclofen hyperpolarized vLGN neurons and its action was reversibly blocked by the selective GABAB antagonist phaclofen (1 mM). In the presence of bicuculline GABA also produced a hyperpolarization that had properties similar to that evoked by baclofen. These results indicate that, although functional GABAA and GABAB receptors are present on vLGN neurons, stimulation of the optic tract evokes only GABAA but not GABAB mediated IPSPs. The lack of long-lasting GABAB IPSPs could explain the absence of long-lasting inhibition observed in vLGN neurons in vivo following stimulation of the optic tract. PMID- 2924153 TI - Electromyographic (EMG) amplitude patterns in the proximal and distal compartments of the cat semitendinosus during various motor tasks. AB - The electromyographic (EMG) signals recorded from the proximal (STp) and distal (STd) compartments of the cat semitendinosus muscle (ST) during treadmill running at various speeds, jumping and paw-shaking were quantified to assess the degree of independence of neural control of the two portions of the muscle. Five adult cats were implanted with intramuscular electrodes in the STp and STd. Raw EMG signals were sampled, rectified and a modified form of their running average was used to calculate the mean EMG every 20 ms. EMG amplitudes of each portion of the muscle were plotted and their relative density distributions were generated. The relative density distribution was used to represent a measure of the probability of any two amplitudes occurring simultaneously (i.e. joint probability density distribution). Based on the probability density distributions of the EMG signals from different movements, the patterns of recruitment from the STp and STd were similar. However, during jumping and paw shaking, two relatively vigorous tasks, some deviations in the pattern were apparent. These data, therefore, suggest that the two ends of the ST are subjected to similar, but not identical, control mechanisms during the motor tasks studied. PMID- 2924154 TI - An analysis of mandibular movement trajectories and masticatory muscle EMG activity during drinking in the guinea pig. AB - Electromyographic (EMG) activity of the anterior digastric, lateral pterygoid, and deep masseter muscles as well as the associated jaw movements during drinking were studied in the awake guinea pig. Drinking was characterized by rhythmic, vertically directed jaw movements with little or no associated lateral movements. The jaw opening phase of each cycle was associated with bilaterally synchronized EMG activity in the digastric and lateral pterygoid muscles, and the jaw closing phase with bilaterally synchronized activity in the masseter muscles. The mean EMG burst durations (+/- 1 S.E.) in the digastric and masseter muscles were 164.2 +/- 14.93 ms and 94.3 +/- 26.44 ms, respectively. The digastric muscle EMG burst duration was significantly correlated with drinking cycle time and with masseter muscle EMG onset; on the other hand, masseter muscle EMG burst duration was not correlated with cycle time. These patterns of EMG activity and jaw movement trajectories are similar to those induced by apomorphine in the ketamine anesthetized guinea pig. PMID- 2924155 TI - Responses of the suprachiasmatic nucleus to retinohypothalamic tract volleys in a slice preparation of the mouse hypothalamus. AB - The electrophysiological responses of the mouse suprachiasmatic nucleus (SCN) to stimulated synaptic input from the retinohypothalamic tract (RHT) were investigated using a hypothalamic slice preparation that includes the entire SCN, optic chiasm and optic nerves. Extracellular recordings of single-unit activity reveal a population of neurons in the ventrolateral SCN that are activated at a median latency of 10 ms after stimulation of the contralateral optic nerve. These neurons apparently receive direct excitatory input from RHT synapses. Other SCN neurons are activated at longer latencies, possibly through input from interneurons. The population field potentials evoked in the SCN by optic nerve volleys consist of a calcium-insensitive transient generated by optic tract axons in the chiasm, followed by calcium-sensitive waves generated by postsynaptic activity. The postsynaptic waves have the form of a field EPSP, negative in the dorsolateral SCN and positive in the ventrolateral SCN, upon which is superimposed a population spike of opposite polarity. The population spike occurs at the same latency as the monosynaptic single unit responses, which were all found near or ventral to the point of reversal of field potential. These findings suggest that neurons in the ventrolateral SCN are excited by synapses on dorsally extended dendrites. The conduction velocity of the RHT in the optic nerve was found to be 0.59 +/- 0.03 mm/ms, while that of the optic tract volley was 2.4 +/- 0.75 mm/ms. The low conduction velocity of the RHT indicates that, within the optic nerve, these axons are thin and/or unmyelinated in the optic nerve. PMID- 2924156 TI - Electric vs magnetic trans-cranial stimulation of the brain in healthy humans: a comparative study of central motor tracts 'conductivity' and 'excitability'. AB - Motor evoked potentials (MEPs) were elicited in the thenar muscles of 11 healthy volunteers via individual electric unifocal and magnetic trans-cranial stimuli (TCS). The effects of TCS strength, of the muscular state (relaxed, contracted) as well as of the amplitude-latency characteristics and the duration of the motor tracts central conduction times (CCTs) to hand muscles, were evaluated and compared between the two types of brain excitation. MEPs with the shortest latency (18.91 +/- 1.31 ms) were recorded in the voluntarily contracted muscle during electric TCS, whilst those with maximal latency (23.3 +/- 1.63 ms) were found after magnetic TCS with an intensity at threshold for eliciting an MEP of about 0.1 mV in the relaxed muscle. Mean CCTs for electric and magnetic TCS calculated in the contracted target muscles, were respectively 5.07 +/- 0.51 and 6.34 +/- 0.46 ms. MEPs with larger amplitudes and durations were observed during magnetic TCS, being maximal when suprathreshold stimuli were delivered. A restricted range of liminar values of magnetic TCS was obtained by defining the threshold for raising motor responses in complete muscle relaxation, indicating that magnetic pulses might represent a useful probe for testing the 'excitability' of the motor tracts. PMID- 2924157 TI - A critical role of the posterior hypothalamus in the mechanisms of wakefulness determined by microinjection of muscimol in freely moving cats. AB - In order to determine critical sites within the hypothalamus responsible for the induction and maintenance of wakefulness (W), we performed microinjections of muscimol, a potent gamma-aminobutyric acid (GABA) agonist, in various lateral hypothalamic regions of freely moving cats. We found that bilateral injections of a small amount of muscimol (0.1-1.0 micrograms/0.5 microliters) in the preoptic and anterior hypothalamus and rostral mesencephalic tegmentum resulted in increased vigilance and insomnia. In contrast, microinjections of muscimol in the middle and anterior parts of the posterior hypothalamus induced long-lasting behavioral and electroencephalographic signs of sleep with short latency. The hypersomnia was characterized by a significant increase in both light and deep slow wave sleep (SWS), and a nearly complete suppression of paradoxical sleep (PS). Animals with muscimol microinjections in the ventrolateral part of the posterior hypothalamus, however, exhibited increased SWS followed by a significant increase in PS. When injected into the posterior hypothalamus of insomniac cats pretreated with p-chlorophenylalanine (PCPA), muscimol induced not only SWS but also PS with short latency. The present data thus support the hypotheses that the posterior hypothalamus plays a critical role in the mechanisms of W and that sleep might result from functional blockade of the hypothalamic waking center. PMID- 2924158 TI - Masseter inhibitory periods and sensations evoked by electrical tooth-pulp stimulation in subjects under hypnotic anesthesia. AB - Sensation and masseter inhibitory periods (MIP) to electrical tooth-pulp stimulation were recorded under hypnotic anesthesia and placebo to local anesthesia. In the first experiment, 8 subjects were tested for the effect of hypnotic anesthesia on sensory detection and MIP at non-painful stimulus levels (mean = 42.1 microA) and painful levels (mean = 86.5 microA). The percentage of detection for non-painful stimuli changed from 94.3% to 14.1% and for painful stimuli from 100% to 28%; both changes were significant (P less than 0.001). Hypnotic anesthesia blocked sensation without interrupting the initiation of the early component of the MIP, but did suppress its late component. In the second experiment, 8 subjects were tested for the perceived intensity of 5 levels of electrical tooth-pulp stimulation under hypnotic anesthesia and placebo. Sensory intensity was measured by the visual analog scale (VAS). Hypnotic anesthesia was significantly more effective than placebo (P less than 0.001) in reducing sensation. The differential effect of hypnotic anesthesia on the early and late component of the MIP lends further support to the hypothesis that hypnotic anesthesia operates primarily at suprasegmental, higher levels in the brain. PMID- 2924159 TI - Prediction of stroke-prone gerbils and their cerebral circulation. AB - We attempted to predict the severity of cerebral ischemia, prior to permanent occlusion of a common carotid artery (CCA), in the gerbil by measuring the diameter of the distal CCA before and during temporary ligation and correlated the severity of cerebral ischemia and the pattern of cerebral circulation. All gerbils with reduction of the diameter over 44% after temporary occlusion developed severe neurological signs following permanent ligation. These gerbils lacked any connection between the left and right anterior cerebral arteries (ACA) and the pericallosal arteries originated from the ACA of the occluded side. No gerbils with reduction of less than 30% developed neurological signs and those gerbils possessed a definite anastomosis between the ACAs from both sides. Six of 7 gerbils without connection between the ACAs whose pericallosal arteries originated from the ACA of the non-occluded side proved to be moderately symptomatic. It was concluded that we could reliably predict severely symptomatic and moderately symptomatic gerbils with specific cerebral circulation patterns prior to permanent occlusion of the CCA. The preselected 'stroke-prone' gerbils should be useful for the investigation of cerebral ischemia and the evaluation of pharmacological agents. PMID- 2924160 TI - Evidence that changes in presynaptic calcium currents are not responsible for long-term potentiation in hippocampus. AB - We used two approaches to test the possibility that changes in presynaptic calcium currents might be responsible for the long-term potentiation (LTP) effect induced by high-frequency stimulation in area CA1 of hippocampal slices. In a first series of experiments, we compared the effect of LTP induction on paired pulse facilitation with that produced by changes in extracellular calcium concentration, a procedure that modifies presynaptic calcium currents during depolarization by changing the ionic gradient for calcium. In hippocampus, as in peripheral synapses, increasing concentrations of extracellular calcium caused a marked reduction in the degree of facilitation obtained with paired-pulse stimulation; LTP, conversely, did not affect the facilitation ratio. The differential effect of changing calcium concentrations versus LTP induction on paired-pulse facilitation was observed with different interpulse intervals as well as in conditions in which the changes in response size produced by the two manipulations were comparable. In the second approach, we measured calcium dependency curves of synaptic responses before and after LTP induction or application of 4-aminopyridine, a blocker of potassium channels that increases presynaptic calcium currents by slowing spike repolarization. Procedures that increase calcium entry into terminals during transmission should shift to the left the sigmoidal function relating extracellular calcium to the slope of the extracellular response. This in turn should result in disproportionate effects of the procedure as a function of the calcium concentration. This prediction was realized with 4-aminopyridine but did not occur following LTP induction: control and potentiated responses were similarly affected by changes in calcium concentration. Although indirectly, these data strongly suggest that LTP is not accompanied by alterations in the presynaptic calcium dynamics associated with transmitter release. PMID- 2924161 TI - Diazepam binding inhibitor-like immunoreactivity(51-70): distribution in human brain, spinal cord and peripheral tissues. AB - We have used a specific radioimmunoassay to describe the distribution of diazepam binding inhibitor-like immunoreactivity (DBI-IR(51-70) in human post-mortem tissues. In brain, highest concentrations were found in the cerebellum, amygdala, hippocampus, hypothalamus and substantia nigra. In the spinal cord, DBI-IR(51-70) was evenly distributed. In peripheral tissues, highest concentrations were found in the liver and kidney. Chromatographic analysis revealed several molecular forms of DBI-IR(51-70) the major form being of greater molecular weight and hydrophobicity than the synthetic fragment peptide. In peripheral tissues, but not in the CNS, a small peak of immunoreactivity was indistinguishable from the synthetic peptide. DBI-IR(51-70) is therefore widespread, but tissue processing may be different. PMID- 2924162 TI - Monoamine and metabolite levels in the prefrontal cortex and the mesolimbic forebrain following neonatal lesions of the ventral tegmental area. AB - Monoamine metabolism was determined in the medial prefrontal cortex (mPFC) and the limbic forebrain (LFB) of adult rats following neonatal lesions of the ventral tegmental area. The dopamine (DA) and serotonin (5-HT) levels were decreased down to 30% in both the mPFC and the LFB. The noradrenaline (NA) level was also significantly decreased, but only in the mPFC of the right hemisphere. The metabolite/transmitter ratios of DA and 5-HT, but not of NA, were greatly increased in the depleted mPFC, but not in the LFB, which suggests an increased activity of the remaining cortical DA and 5-HT fibres in the mPFC. PMID- 2924163 TI - Feeding increases extracellular serotonin in the lateral hypothalamus of the rat as measured by microdialysis. AB - Microdialysis probes inserted into chronically implanted guide shafts allowed the collection of serotonin and 5-hydroxyindoleacetic acid (5-HIAA) from the lateral hypothalamus of rats during feeding behavior. After the collection of baseline samples, animals were offered a palatable diet that they could only see and smell for 60 min, then they were allowed access to the food for an hour. An additional three samples were collected after food was removed. Extracellular serotonin increased during the first half hour of access when the animals actually ate the food, and then returned to baseline level throughout the remainder of the test. 5 HIAA decreased gradually with no increase during feeding. These data suggest that eating a meal of palatable food causes a short-term increase in extracellular serotonin in the lateral hypothalamus. This increased serotonin may play a role in the control of lateral hypothalamic feeding and reward. PMID- 2924164 TI - A sense of movement elicited in paralyzed distal arm by focal magnetic coil stimulation of human motor cortex. AB - Two magnetic coils (MCs) of special design (Cadwell Laboratories) were used to elicit movements predominantly of one or a few digits by percutaneous stimulation of human motor cortex. When cortically elicited movements were ischemically blocked, the MC still elicited a discrete sense of digit movement; a sense of movement map was constructed by stimulating at different scalp sites. Our findings support the existence of corollary discharge. PMID- 2924165 TI - Neuronal damage following repeated brief ischemia in the gerbil. AB - The effect of repetition of brief ischemia, which causes no morphological brain damage when given as a single insult, was studied. Two-minute forebrain ischemia was induced in gerbils singly and 3 or 5 times at 60-min intervals. Although 2 min ischemia induced no neuronal damage, 3 or 5 repeated ischemic insults caused neuronal damage in the selectively vulnerable regions, the severity being dependent on the number of episodes. PMID- 2924166 TI - EMBOPRO--an automatically generated protein sequence database. AB - For the identification of newly sequenced proteins it is necessary to have a large stock of known proteins for comparison. In this paper we present an automatically generated protein sequence database. The translation program introduced allows a periodical translation of every new release of the EMBL database. Possible errors of the translation are discussed as well as the reliability of the nucleotide sequence data, which turns out to be quite good. A comparison of our translated database with some established ones is given. PMID- 2924167 TI - A simple add-on algorithm to extend one-dimensional finite difference diffusion calculations to include charge coupling. AB - The importance of interionic charge coupling in chemical and biological diffusion problems is discussed, and the Nernst-Planck (ionic) and Onsager-Fuoss (neutral component) methods are considered. A novel single pass charge-coupling algorithm 'Q-COUPLE' is proposed, which should be usable as a separate add-on subroutine with many one-dimensional finite difference diffusion calculations. Its mode of operation is explained with the help of elementary electrostatics and by reference to listings in BASIC. The algorithm is being applied in a finite difference model of diffusion-with-reaction in dental plaque, with 12 ions or ionizable molecules diffusing and interacting with fixed charges. It is shown to be invariant with respect to the direction of sweep, and in the simple case of coupled diffusion of a single polyvalent electrolyte is found to compare well with the analytical solution. Advantages and limitations of the proposal are discussed. PMID- 2924168 TI - Chaos: principles and implications in biology. AB - In this paper we review some of the basic principles of the theory of dynamical systems. We introduce the reader to the definition of chaos and strange attractors and we discuss their implications in biology. PMID- 2924169 TI - The frequency of oligonucleotides in mammalian genic regions. AB - The large body of nucleic acid sequence data now available offers a unique opportunity for the characterization of individual oligonucleotides which may be specific to sequence functional domains. We have prepared algorithms for the study of the frequency distribution of all oligonucleotides of length 2-6 in DNA sequences. We have implemented them in the study of 634 mammalian DNA sequences spanning 1.782 Mb, and have obtained the distribution of the ratio between the observed frequency of oligonucleotides and their expected frequency based on independent nucleotide probabilities. We then studied the distribution of oligonucleotides (or k-tuples) of each length in a subset of 129 complete mammalian genes spanning 0.607 Mb. Eight distinct genomic regions, namely 5'-non transcribed, first exon, first intron, intermediate exons, intermediate introns, last intron, last exon and 3'-non-transcribed, were considered. We observed that some oligonucleotides show a statistical behaviour and a regional distribution similar to that of known signal sequences. Moreover the frequency distribution of oligonucleotides of length 5 and 6 tends to become bimodal, indicating the existence of a population of very frequent oligonucleotides. PMID- 2924170 TI - A compact, flexible and cheap system for acquiring sequence data from autoradiograms with a digitizer and transferring it to an arbitrary host computer. AB - In this article we describe MS-EdSeq, an integrated system for fast and accurate gel reading combined with safe and automatic file transfer to an arbitrary host computer. The uniqueness of MS-EdSeq is its way of forming a link between the interactive sequence editor on the PC and the potential of the minicomputer acting as a host, thus making optimal use of both systems. This is especially suited for the moderately sized research group, using DNA-sequencing as one of various biochemical methods, where PCs are already in use for other tasks and a minicomputer is available. The gel reading algorithm described is fast, accurate and simple and the file transfer relies on the safe and well-known Kermit programs. PMID- 2924171 TI - SDSE: a software package to simulate the evolution of a pair of DNA sequences. AB - An algorithm to simulate DNA sequence evolution under a general stochastic model, including as particular cases all the previously used schemes of nucleotide substitution, is described. The stimulation is carried out on finite, variable length, DNA sequences through a strict stochastic process, according to the particular substitution rates imposed by each scheme. Five FORTRAN programs, running on an IBM PC and compatibles, carry out all the tasks needed for the simulation. They are menu driven and interfaced to the system through a principal menu. All sequence data files used and generated by the SDSE package conform to the standard GenBank database format, thus allowing the use of any sequence retrieved from this databank, as well as the application of other packages to analyse, manipulate or retrieve stimulated sequences. PMID- 2924172 TI - MULTAN (2), a multiple string alignment program for nucleic acids and proteins. PMID- 2924173 TI - CLEAVAGE: a microcomputer program for predicting signal sequence cleavage sites. PMID- 2924174 TI - Using Lotus 1-2-3 to determine correlation of linearly related method comparison data. PMID- 2924175 TI - The total fundoplication gastroplasty: surgical procedure and radiologic appearance. AB - The total fundoplication gastroplasty (TFG) consists of a combination of an esophagus-lengthening Collis gastroplasty and suturing of the gastric fundus to the esophagus and neo-esophagus to produce a stable intra-abdominal segment together with a complete Nissen fundoplication tailored in length to control reflux and avoid overcompetence. We studied 50 patients at least three months after TFG with an upper gastrointestinal examination and a tube esophagogram. Tube esophagography enhances distension of the esophagus and esophagogastric junction and eliminates the barium pool often seen in the distal esophagus in double-contrast esophagography. With this technique we were better able to understand the radiologic anatomy of the esophagogastric junction following TFG. Tube esophagography provided additional radiologic information in the five patients (10%) with preoperative peptic strictures of the esophagus. We describe the surgical and radiologic anatomy of the TFG, the technique of postoperative radiographic examination, and the postoperative problems we have encountered. PMID- 2924176 TI - Fibromatosis of the brachial plexus and shoulder girdle. AB - Fibromatosis is a term which encompasses a group of non-metastasizing fibroblastic tumors which tend to invade locally and recur after attempted excision. Although it frequently involves the shoulder region and brachial plexus, it has seldom been reported in the radiological literature. Five patients with disease involving this location are described. On computed tomograms the tumors appear as isodense irregular masses infiltrating adjacent muscles, especially the serratus anterior and the scalene muscles, without cystic or necrotic changes. The appearances are not specific but the diagnosis should be considered in such brachial plexus lesions. Computed tomography plays an important part in the preoperative management and follow-up of this entity. PMID- 2924177 TI - The effective dose equivalent in radiology. PMID- 2924178 TI - Phentolamine for enhanced visualization of distal arteries in lower extremity arteriography. AB - To augment visualization of the distal arteries, phentolamine was administered to 83 patients (164 limbs) undergoing lower extremity arteriography. Arterial visualization was graded into three classes and skin temperatures were recorded. Phentolamine provided very good visualization of the distal arterial bed in 95% of limbs. A strong correlation was observed between the temperature rise of the feet and the class of arterial visualization. No side effects were recorded. The use of phentolamine in lower extremity arteriography is recommended. PMID- 2924179 TI - Intracystic papillary breast carcinoma in a 55-year-old man: radiologic and pathologic correlation. AB - Radiographic manifestation of intracystic papillary male carcinoma is presented along with its histopathological correlation. The prognosis, differential diagnosis, and natural history as well as possible sites of origin are discussed. PMID- 2924180 TI - Diagnosis of Legionella lung abscess by percutaneous needle aspiration. AB - Pneumonia is a life-threatening infection of immunocompromised patients, and accurate identification of the causative agent is essential for early initiation of appropriate antibiotic therapy. Percutaneous needle aspiration was used to identify Legionella pneumonia after sputum and bronchoscopy specimens had failed to provide a diagnosis in a 13-year-old leukemic patient with a lung abscess. We believe this is the first report of a child with this disease diagnosed in this way. PMID- 2924181 TI - Evolution of a mycotic aneurysm of the thoracoabdominal aorta. AB - We report a patient with septicemia who developed a mycotic thoracoabdominal aortic aneurysm over a six-week period. The value of contrast-enhanced computed tomography in the diagnosis of mycotic aneurysms of the aorta is stressed. PMID- 2924182 TI - Gastric torsion. AB - We report a seven-week-old baby girl with a one-day history of vomiting and respiratory distress. The radiological findings were those of intrathoracic mesenteroaxial torsion of the stomach complicating a large hiatus hernia which included part of the small bowel and colon with partial colonic obstruction. This is a rare but important cause of alimentary tract obstruction and respiratory distress in infants. Prompt diagnosis and correction are vital. PMID- 2924183 TI - Unusual presentation of non-Hodgkin lymphoma of the spleen. AB - We report a patient with highly malignant primary centroblastic lymphoma of the spleen (diffuse, large non-cleaved cell type). The tumor presented as splenomegaly due to a large mass containing diffuse punctuate calcifications. The latter have not been previously described as a radiological finding in this neoplasm. PMID- 2924184 TI - Buttock abscess complicating Crohn's disease. AB - Two patients with buttock abscesses developing as an extension of Crohn's disease are described. In each, the abscess extended through the sciatic foramen into gluteal soft tissues. Cross-sectional imaging, particularly computed tomography, is of major help in identifying these lesions and the pathway of spread. PMID- 2924185 TI - Colonic aphthous ulcers in pseudomembranous colitis. AB - Colonic aphthous ulceration is usually due to Crohn's disease. It has been described in other colitides but has not been reported in pseudomembranous colitis. We report a patient with pseudomembranous colitis with aphthous ulceration demonstrated by barium examination. PMID- 2924186 TI - Radiological contrast media. AB - 1. This author believes that the present evidence (water shifts and vasodilatation) strongly indicates that low osmolality is probably the main advantage of the new contrast media. 2. Arteriographic adverse reactions (pain, vasodilatation) are less marked with the contrast medium of the lowest osmolality -i.e. ionic ioxaglate salts. 3. Minor adverse reactions (nausea and vomiting) are less marked with some non-ionic media (e.g. iohexol, iopamidol) than with ioxaglate but there are no data concerning the relative incidence of severe reactions or fatalities. 4. Dr. Lasser's suggestion in 1987, that 12 hours of corticosteroid prophylaxis reduces the adverse reaction rate of intravenous HOCM to the rate of LOCM reactions, awaits confirmation. However, corticosteroid prophylaxis will not reduce the side effects due to hyperosmolality, e.g. vasodilation, hypervolemia, and pain (on arterial injection). 5. Unless and until the necessary finances are available, I suggest LOCM (costing 12 times the price of HOCM in Canada and America) be used on a selective and discriminatory basis in three groups of patients: those undergoing painful procedures (e.g. peripheral arteriography), those undergoing potentially dangerous procedures (e.g. spinal angiography, coronary angioplasty) for patients considered on account of their previous medical history (e.g. asthma, allergy, previous adverse reactions, cardiac failure) to be at greater risk than the normal population. PMID- 2924187 TI - [Hemodynamic and gasometric modifications during the anesthesia recovery period in patients undergoing ventilation after surgery of the abdominal aorta]. AB - This study was carried out on 12 patients (mean age 61) in order to assess the oxygen consumption (VO2) in the post-operative stage of an elective surgical procedure (replacement of the abdominal aorta). Anesthesia was a combination of thiopentone, pancuronium bromide and high doses of droperidol and fentanyl. Patients were kept intubated and ventilated in the post-operative period. VO2 and other related metabolic parameters as well as hemodynamic parameters were measured every 45 minutes over a period of 5 hours. A VO2 increase (127%) related to the increase in body temperature was noted. Mean VO2 for all patients during the whole period was 170 +/- 13 ml.min-1.m-2 (range: 51-411 ml.min-1.m-2). Mean value of maximal VO2 was 240 +/- 21 ml.min-1.m-2 (range: 1471-411 ml.min-1.m-2). Large dose of droperidol are shown to limit VO2 increase. In patients with shivering, the maximal value of VO2 was found during shivering. The amount of droperidol administered during anesthesia was greater in patients without shivering. VO2 increase was due to a rise in tissular O2 extraction. Cardiac index was insufficiently increased (+ 9.4%) and a certain extent of myocardial inadaptability was suspected in relation with: high blood pressure, hypovolaemia and/or myocardial effect of anesthesia agents. PMID- 2924188 TI - [Management and emergency therapy of acute renal insufficiency in the adult]. PMID- 2924189 TI - Septic shock. PMID- 2924190 TI - National commission rejects RCTs, recommends shortage solutions. PMID- 2924191 TI - What nurses should know about the budget process. PMID- 2924192 TI - New law on disclosure of AIDS test results. PMID- 2924193 TI - Computer graphics. A tool for decision making in nursing. AB - The use of computer graphics in nursing has not yet reached its full potential. Graphs or maps can display large amounts of data so that critical elements can be inspected in a minimal amount of time. This article discusses computer graphics in terms of their use in nursing and the need for this electronic modality in nursing curricula. PMID- 2924194 TI - Levels of computer education for professional nursing. Development of a prototype graduate course. AB - Leveling computer education for professional nurses at the undergraduate and graduate levels is presented via a four-tiered model. Foundational course content at level 2 for all graduate nursing students preparing for advanced nursing roles is described. A quasi-experimental study (N = 80) demonstrated the effectiveness of the course in terms of the attitude changes toward computerization and perceived knowledge about computer applications in nursing. PMID- 2924196 TI - Encouraging the growth of computer applications in nursing. PMID- 2924195 TI - Designing a test bank computer program. AB - This article contains all of the instructions needed to create a computerized test bank program. The program is flexible enough to allow for the sequential numbering of test items; the alteration of stems, distractors, and options to develop new test items; and the programmability to produce a hard copy objective examination, as designed by the user. PMID- 2924197 TI - Difficulties faced by software users. PMID- 2924198 TI - Partners in thought. PMID- 2924199 TI - Compiling an information network. PMID- 2924200 TI - Computer network as a vehicle for the delivery of nursing services. PMID- 2924201 TI - Development of a statewide Maternal and Child Health Information Network. AB - The Maternal and Child Health Information Network (MATCH) was a national demonstration project funded in 1983 by a Special Projects of Regional and National Significance (SPRANS) grant. The network's major objectives have been to correlate collected clinical service data items into usable information, to expand the database through linkage with other systems within the Ohio Department of Health, and to analyze the conjugated data in an effort to expand current knowledge of maternal and child health. The network is interactive between local funded agencies and the state Health Department. Both data entry and data retrieval are distributed at the end-user information centers. Training and support, major components of the project, are provided to each participant and user of the network. One advantage of MATCH is that it allows linkage of clinical service records with vital records as an outcome of prenatal care and/or a history for child health clients. This aspect of the system permits an expanded look at the population being served by funds designated for maternal and child health programs and the ultimate outcome of such services, and permits comparison with those not receiving preventive health services. PMID- 2924202 TI - [The mother and infant with Steinert's myotonic dystrophy]. AB - Pregnancy and delivery present a number of risks for the mother suffering from myotonic dystrophy, and for her infant. Most of the time, she does not even know that she is affected by the disease and a carrier of the gene. We review the complications of pregnancy and delivery in myotonic patients, and propose a simple management with specific items for each gestational period. The child of a dystrophic mother has a 50% risk of inheriting the abnormal gene. He may also exhibit a developmental and malformation syndrome called "congenital myotonic dystrophy". From the beginning, he may show respiratory distress, thereafter inability to swallow and severely hypotonia. Later, he may demonstrate mental retardation. Some of the most obvious signs found in neonates in our practice are illustrated. We also add a few tests to the list of those already recommended for these children. PMID- 2924203 TI - [Myotonic dystrophy: I. Socioeconomic and residential characteristics of the patients]. AB - Myotonic dystrophy is a dominantly inherited genetic disorder which, in medical literature, has been linked to peculiar socio-economical conditions. In order to document this assertion, a sociological study was conducted in the Saguenay-Lac Saint-Jean region (Quebec), using a representative sample (N = 218) drawn from the myotonic dystrophy population. A study of the patients' places of residence was also carried out. The results clearly indicate that myotonic dystrophy patients exhibit a socio-economic profile associated with disadvantaged milieux: high unemployment, low income and limited schooling. Many of these patients must rely on social welfare. Two families out of five (42%) live beneath the poverty line. The wage-earning history of these persons is closely linked to their self evaluation of their working capabilities. After the age of forty, a high proportion of these people are unable to hold down a paying job and claim they are unable to do so. Within a well-screened urban area, a study of the patients' places of residence indicates census tracts where myotonic dystrophy is concentrated (ecological niches). These social areas are close to the downtown area and display characteristics of disadvantaged milieux. Accordingly, the My D gene seems to be confined to a specific socio-economic and socio-geographical environment, through which the spread of the gene is channelled among the population. PMID- 2924204 TI - [Myotonic dystrophy: II. Marital status, fertility and gene transmission]. AB - A sociological study, using a representative sample (N = 218) of the myotonic dystrophy population, made possible an analysis of the relationship between certain demographic characteristics (marriage, fertility) and the mechanisms involved in the transmission of the deleterious gene. The results show a clear differentiation between the marriage rate of women and men affected by myotonic dystrophy. Whereas men show a considerable decline in marriage eligibility, women continue to marry at a young age and in a proportion almost equal to that of the unaffected population. The study also indicates that the average fertility rate among married patients in the Saguenay-Lac-Saint-Jean exceeds the fertility rate reported from affected populations found in other countries. Our study shows an above-normal male fertility rate. This demographic fact explains the overrepresentation of male transmitters noted in the affected population. However, if present trends remain unchanged, women will be more likely to transmit myotonic dystrophy to future generations. These conclusions illustrate how the transmission and spread of a dominant gene follow a pattern that cannot be dissociated from the socio-cultural characteristics taken as a whole, particularly demographic characteristics. They also provide us with useful avenues for setting up future prevention programmes. PMID- 2924205 TI - Origin and diffusion of the myotonic dystrophy gene in the Saguenay region (Quebec). AB - A very high prevalence (approximately 1/475 in 1985) of myotonic dystrophy (Steinert disease) is observed in the Saguenay region, which is located in the north-east part of the Province of Quebec. For various reasons, however, the literature on the subject generally associates a high degree of selective disadvantage with this gene, which seems to contradict the Saguenay data. Using a computerized regional population register, we have reconstituted patients' genealogies and family biographies. We have thus been able to study the origin of the gene and to compare the demographic behavior of patients and controls. On the whole, patients seem to be very little disadvantaged compared to controls, in terms of reproduction as well as of geographical and occupational mobility. PMID- 2924206 TI - Myotonic dystrophy in Quebec: geographical distribution and concept of genetic homogeneity. AB - The geographical distribution relative to place of residence of patients with myotonic dystrophy (MD) and admitted to a Quebec hospital during a five year period (1980-1984) is presented and discussed. The sample consists of 72 males and 68 females of varying ages over 10 years. Analysis of the data shows a North Shore distribution of patients in a cline from Saguenay-Lac-St-Jean, through Quebec City and to Montreal. However, a low prevalence is apparent on the South Shore, east of Quebec City, for which an historical and genealogical explanation are discussed. This geographic distribution favours the hypothesis of genetic homogeneity for the MD gene in the Quebec population. A stronger second argument comes from genealogical studies of 10 families sampled from the Chicoutimi Muscular Dystrophy Clinic. Genealogical paths traced to ancestors who founded Charlevoix for these 10 families go back to a cluster of 25 founders, one of whom must have been the carrier of the MD gene. The probative third argument for genetic homogeneity comes from the allelic distribution of the apolipoprotein E (ApoE) gene in the Quebec City, Saguenay and in families with MD. The ApoE locus is on chromosome 19 and closely linked to MD. In MD-affected individuals there is a linkage disequilibrium for the epsilon 4 allele while non-MD members of these families show allelic frequencies not differing significantly from the control population.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2924207 TI - Hypertriglyceridemia and lower LDL cholesterol concentration in relation to apolipoprotein E phenotypes in myotonic dystrophy. AB - Plasma lipid, lipoprotein levels and apolipoprotein apo E phenotypes were determined in 70 patients with myotonic dystrophy (MyD) and 81 controls. Marked differences were noticed in the apo E phenotype frequencies between the two groups. Plasma triglycerides and VLDL cholesterol were higher in MyD than controls, but only the latter was related to differences in the apo E phenotypes between two groups. Accordingly, the ratio of VLDL cholesterol/plasma triglycerides was increased significantly in MyD, suggesting accumulation of intermediary density particles due to lower affinity of E2 containing lipoproteins for lipoprotein cell receptors. The LDL cholesterol concentration was lower in MyD than controls and was related to differences in the apo E phenotype frequencies between the two groups. These results indicate increased removal of LDL particles in the apo E2 phenotypes, perhaps due to upregulation of LDL (B, E) receptor activity. Plasma cholesterol and HDL cholesterol concentrations were similar in both groups. Another feature of the study was lower levels of plasma cholesterol, triglycerides, VLDL and LDL cholesterol in the homozygous E4:E4 phenotype. These results suggest increased clearance rate of both VLDL and LDL particles and support the concept that apo E4-containing lipoproteins have higher in vivo affinity for ape E and/or B, E receptors. PMID- 2924208 TI - Myotonic dystrophy: linkage with apolipoprotein E and estimation of the gene carrier status with genetic markers. AB - The genes for myotonic dystrophy (MD) and for apolipoprotein E (ApoE) belong to a chromosome 19 synthenic group of markers. A familial linkage analysis between MD and ApoE was performed using the J Ott LIPED program (IBM PC/XT, April 1984) to estimate the genetic distance between these 2 genes. Of a total of 136 individuals in 11 MD families, 81 were confirmed to be affected by the disease and 41 were asymptomatic. ApoE phenotypes were determined in 115 of these 122 individuals. No recombinant was observed out of 74 meioses which were informatives for both MD and the ApoE isoproteins. A global maximal lod score Z of 19.00 was obtained at the recombination fraction theta = 0. The upper theta value at the confidence interval corresponding to the peak lod score (Z max) - 1 was 0.03. This suggests that the loci for MD and ApoE are at a distance of 0 to 0.03 Morgan. Since ApoE and apolipoprotein C2 (ApoC2) have been shown by others to be about 40 kb apart, our data are therefore consistent with the distance estimate of 0.02 Morgan reported between MD and ApoC2. The D19S19 (LDR152) polymorphic DNA sequence is also tightly linked to MD on chromosome 19. The segregation of ApoE isoproteins and of ApoC2 and D19S19 DNA polymorphism was utilized for evaluating the probability for individuals at risk of inheriting the disease gene in MD families. Data are presented on 3 families to emphasize the usefulness of genetic markers to estimate the MD gene carrier status of asymptomatic individuals and also for those presenting a partial syndrome. The limitations of such approach are also discussed. PMID- 2924209 TI - Effect of knee joint angle on a heteronymous Ib reflex in the human lower limb. AB - Altered efficacy, from change in receptor discharge with different positions of the knee, was investigated in a heteronymous Ib reflex of the human leg. The electrical stimulus was low threshold, to the common peroneal nerve. The divergence of the group I afferents was studied in the electromyograms (EMGs) of ipsilateral and contralateral thigh muscles. The stimulus evoked ipsilateral, short latency, excitation in the three quadriceps muscles studied and inhibition in the knee flexor semitendinosus (ST), with prior contraction of target muscles. This excitation and inhibition did not alter when studied over the range of the knee joint. The stimulus did not evoke responses in contralateral thigh muscles, contracted or relaxed. It is concluded that (1) any change in convergence from discharge of receptors, during extension of the limb, is small and sub-threshold, and (2) this spinal proprioceptive level of neural control appears to be directed primarily to the single limb. PMID- 2924210 TI - Vascular headache: a presenting symptom of multiple sclerosis. AB - Vascular headache of migraine-type may be a presenting symptom of multiple sclerosis (MS), a condition usually not considered in the differential diagnosis of a severe headache accompanied by neurological signs. We reviewed records of 1,113 patients with MS seen from 1967-1987 and found 44 cases whose initial attack or subsequent exacerbations were heralded by a migraine-type headache. Twenty-seven patients had no prior history of migraine, and of these, 12 presented simultaneously with their first headache and MS attack. Twenty-three patients had symptoms of a posterior fossa mass lesion. The significance of these results and possible pathogenesis is discussed. PMID- 2924211 TI - Sensory neuron degeneration in familial Kugelberg-Welander disease. AB - A 53 year old man developed symptoms of motor neuron disease in childhood. There was a family history of a similar disorder and it was felt to represent a form of Kugelberg-Welander disease. In addition to the motor deficits, sensory abnormalities in his legs were documented during life. Autopsy revealed anterior horn cell loss throughout the length of the spinal cord, with preservation of the phrenic nucleus. The lumbar dorsal root ganglia showed active degeneration of sensory neurons, with nuclear changes exceeding cytoplasmic ones. The fasciculus gracilis showed Wallerian degeneration. The findings provide direct evidence that sensory neurons can degenerate in some forms of motor neuron disease, and that the "demyelination" or "degeneration" of posterior columns sometimes seen in the various forms of motor neuron disease may actually be secondary to cell body disease in the dorsal root ganglia. PMID- 2924212 TI - Sturge-Weber-Dimitri disease: role of hemispherectomy in prognosis. AB - We report 12 patients with Sturge-Weber-Dimitri disease treated surgically between January 1975 and December 1987. Hemispherectomy was performed on ten, two others underwent occipital lobectomy for intractable seizures. All operations were performed between the ages of 3 months and 20 months, except in two at age 8 and 9 years. The onset of seizures in all was between 2 and 8 months of age, except for two at 15 months. There were no postoperative deaths. Postoperative shunt procedures were required in 3 out of 12 (25%). Postoperative seizure control for one year or more was achieved in 11 out of 12 patients. The remaining patient is on medication with no seizures, but follow-up is less than a year. Intellectual deterioration was not seen after surgery except in 2 patients who had late operations. We conclude that patients with Sturge-Weber-Dimitri syndrome who have intractable seizures in the first 6 months of life and unilateral hemispheric involvement should be considered for early resection of the involved hemisphere. PMID- 2924214 TI - Steinert's disease or myotonic dystrophy "a disease unlike others". PMID- 2924213 TI - Isolated basilar artery occlusion associated with a clivus fracture. AB - Most vascular injuries to the brain secondary to blunt head trauma involve the internal carotid circulation. A case of isolated basilar occlusion secondary to a clival fracture is described and compared to three other cases in the literature. PMID- 2924215 TI - [Phenotype variability in Steinert's myotonic dystrophy]. AB - Myotonic dystrophy, best known in the French literature as Steinert disease, is a dominantly inherited disorder. When the gene is fully expressed, it shows a characteristic clinical picture. Myopathy and myotonia are the main features, but this is a systemic disease which may involve many other organs such as the central nervous system, eyes, bones, endocrine system, etc. With the complete picture, physical and behavioral features make the diagnosis easy, only to be confirmed by neurological and ophthalmologic examination and/or electromyography. This work reviews the main clinical signs seen in the classical form of the disease. We also want to stress the variability of that picture. Finally, we describe a new dysmorphic sign in myotonic dystrophy: large prominent cupped auricles. Although not recognized, prominauris has been illustrated in a number of publications on myotonic dystrophy. Three of our adult male patients presenting the congenital form of the disease at birth have been investigated to rule out concomitant fragile-X syndrome. Both syndromes include mental retardation and dysmorphic ears. Our patients show the usual testicular atrophy, whereas the fragile-X syndrome includes testicular hypertrophy. Cytogenetic studies were normal. Old clinical description and new physical signs may lack prestige in the perspective of recent molecular biological breakthroughs, but to recognize the disease and help patients live with it will always be the role of practitioners. PMID- 2924216 TI - Partial syndrome of myotonic dystrophy: clinical presentation and follow-up. AB - The neurological and ophthalmological investigation of 602 members of 88 Saguenay kindreds affected by myotonic dystrophy (MyD) revealed 130 persons with a partial syndrome. These patients, whose average age was 34.1 years, showed different abnormalities such as particular ophthalmic and/or neuro-muscular signs, suggesting MyD in the absence of myotonia or typical lens abnormalities. After an average period of 2.4 years, 44 of these 130 patients were reassessed by the same neurologists and ophthalmologists. Thirty still had a partial syndrome, 8 showed a typical form of MyD and 6 no longer presented any identifiable anomaly. This preliminary follow-up study of the partial MyD syndrome did not allow us to identify any clinical anomaly from which the presence of the MyD gene could be predicted in a significant way. It furthermore suggested that the identification of equivocal or unspecific signs among these patients can sometimes lead to misdiagnosis. This must be taken into account when providing genetic counselling. It furthermore indicates that the use of DNA probes is essential for a reliable identification of asymptomatic MyD gene carriers. PMID- 2924217 TI - Isokinetic peak torque and work relationship in the laterally unstable knee. AB - The purpose of this investigation was to assess the relationship between the isometric and isokinetic peak torque (speed of movement 0 degrees, 60 degrees, and 180 degrees/s) and the total work output of multiple contractions (180 degrees/s) of the quadriceps and hamstrings in subjects suffering from a chronic insufficiency of the lateral ligament compartment (LAT) of the knee. At every test speed the Pearson product moment (r) and the Spearman rank (rs) correlation coefficients between the peak torque and total work were highly significant for both muscle groups in the uninjured (r = .87-.97, rs = .86-.93) as well as in the laterally unstable (r = .65-.90, rs = .71-.90) knees. In both knees and in both muscle groups the correlation coefficients increased towards the highest speed of the isokinetic movement, obviously since the total work was registered at that speed. In conclusion, concerning laterally unstable knees the total work analysis may offer little additional information to that attained by more simple measurement, the peak torque analysis. PMID- 2924218 TI - Validity of the 20 m shuttle run test with 1 min stages to predict VO2max in adults. AB - The purpose of this study was to assess the validity of the 1 min stage version of the 20 m shuttle run multistage test to predict VO2max in adults (53 males and 24 females, 19 to 47 years old). The maximal shuttle run speed (S-MAS) was thus compared to the VO2max attained during a multistage treadmill test (TE-VO2max), the retroextrapolated VO2max at time zero of the O2 recovery curve of the shuttle run (SR-VO2max) and the VO2max predicted from a previously developed regression equation with children (Mercier et al., 1983) and putting 18 year olds in the regression equation for all adults which yielded (SP-VO2max = -27.4 + 6.0 S-MAS). The latter regression equation was very similar to the ones obtained with the two other criteria and was thus retained to ensure a smooth transition between children and adults in predicting VO2max. Correlations and standard errors of the estimate between S-MAS and TE-VO2max (r = 0.90 and Syx = 4.4) or SR-VO2max (r = 0.87 and Syx = 4.7) were quite good. TE-, SR- and SP-VO2max were also similar (mean +/- SD = 49.4 +/- 10.1, 48.8 +/- 9.3 and 47.1 +/- 8.3 mL.kg-1.min-1, respectively, p greater than 0.05). It was concluded that the 20 m shuttle run is a valid test to predict VO2max in adults. PMID- 2924219 TI - Expert--novice differences in perception: how expert does the expert have to be? AB - Twelve expert and 15 novice badminton players viewed a film task which attempted to simulate the perceptual display of the sport of badminton. The film task varied in terms of visibility to either specific time periods of display information or to specific spatial areas of the display, and the subject's task was to determine whether the stroke being viewed had a cross-court or a down-the line destination. In keeping with an earlier study (Abernethy and Russell, 1987a), expert players were shown to have a unique capability to decrease their prediction errors at an earlier point in the stroke sequence than could novices, but unlike the previous study this could not be attributed to the experts' superior use of arm cues. The robustness of expert--novice differences in perceptual strategy across changes in the level of expert--novice differentiation are discussed. PMID- 2924220 TI - Game standings and psychological crisis in sport: theory and research. AB - Individual psychological crisis in competitive situations negatively affects motor performance. Psychological crisis development is probabilistically defined for every moment of the competition. This study estimates the effect of game standings defined interactively by three components: direction of lead, tendency, and event's expectancy, upon crisis vulnerability of a basketball player. Twenty eight top basketball experts responded to a 'Game Standing Questionnaire' in which they were asked to assess probabilistically the relevance of game standings to crisis development. The Bayesian likelihood ratio was applied to these estimates. Results revealed that game standings have a considerable diagnostic relevance with regard to the development of an individual competitive psychological crisis. Furthermore, a negative tendency, a lead by the opposing team, and an unexpected event are more likely to occur under crisis conditions than under non-crisis conditions. Various aspects related to the validation and the practical applicability of the study are discussed. PMID- 2924221 TI - [Stability in shooting: the effect of expertise in the biathlon and in rifle shooting]. AB - The aim of this study is to compare the body-gun stability of biathletes and rifle shooters up to the firing of a shot, when shooting in standing position. Eight subjects are tested: two experts and two novices in rifle shooting, two experts and two novices in biathlon. Electromyographic (EMG) activity of the tibialis anterior, gastrocnemius and deltoid muscles, as well as rifle oscillation and centre-of-pressure displacements were recorded during a set of ten shots per subject. The results revealed that expert biathletes seem to use a different strategy than expert rifle shooters, each of them adapting to the characteristics of their respective discipline. No significant pattern emerged from tests with novice rifle shooters, as their scores correlated only weakly with the various parameters measured in this study. PMID- 2924222 TI - Anaerobic performances of sedentary and trained subjects. AB - The objective of this report was to compare the performance of sedentary individuals, physical education students, and athletes of various disciplines in 10 s and 90 s maximal cycle ergometer tests. The 10 s power was the highest power output in one second from the 10 s test, while capacities were defined as the total work output during the best 10 s trial and the 90 s test. ANOVA and Duncan multiple range test indicated that the mean values of the 10 S power and capacity and the 90 S capacity tests were significantly higher in sprinter than in sedentary groups. Sprinters performed significantly better than marathon runners only in the 10 s capacity and power. Bodybuilders and sedentary subjects had similar results in the 90 s capacity test. Mean performance values per kilogram of body weight in sedentary females reached about 60% of sedentary males while marathon runners, physical education students and sprinter females reached about 80% of the male performances for the three indicators. When expressed per kilogram of fat-free mass, females reached a higher proportion of the male values for all performances. These results indicate that: a) there are differences for the power and capacity measured in predominantly anaerobic tests between athletes from different disciplines and sedentary individuals, and b) gender differences exist for these anaerobic performance indicators, but they appear attenuated in trained subjects. PMID- 2924223 TI - The measurement of cohesion in sports teams: the Group Environment Questionnaire. PMID- 2924224 TI - Euthanasia in The Netherlands. PMID- 2924225 TI - Tobacco use in health care institutions. PMID- 2924226 TI - Evaluating treatment for alcoholism. PMID- 2924227 TI - "Late neonatal deaths" and infant mortality rates. PMID- 2924228 TI - AIDS testing: mathematical models. PMID- 2924229 TI - Occupational stress reactions: lessons for management. PMID- 2924230 TI - Physicians' participation in establishing criteria for hypertension management in the office: will patient outcomes be improved? AB - We designed this study to determine whether an intensive 1-day educational workshop involving family physicians in establishing essential criteria for hypertension management would significantly affect the short-term outcomes of hypertensive patients in their practices. Forty randomly selected physicians were separated into three groups: those who would be involved in establishing the criteria (15), those who would receive the criteria by mail (15) and those who would act as controls and not be aware of the criteria (10). We found no significant difference between the three groups in the number of hypertensive patients whose condition remained uncontrolled after the intervention. We conclude that physicians' participation in the establishment of standards of care for conditions such as hypertension or their awareness of such standards does not independently result in significantly better patient outcomes. Consequently, we recommend that physicians and health care planners concerned with improving outcomes not rely on any single intervention strategy when planning change. PMID- 2924231 TI - An audit of blood component therapy in a Canadian general teaching hospital. AB - As part of a quality assurance program a retrospective audit of transfusion practices for packed red blood cells, fresh frozen plasma and albumin was undertaken with predetermined criteria in a general teaching hospital. Of 520 transfusion episodes with 1218 units of packed red blood cells given to 297 patients 88% were considered appropriate; of 106 episodes with 405 units of fresh frozen plasma given to 83 patients 90% were deemed appropriate; and of 187 episodes with 320 units of albumin given to 99 patients 64% were considered appropriate. The results of this audit, when compared with those of other surveys of blood use in a similar population, suggest that pretransfusion approval of requested components would reduce the number of inappropriate transfusions. PMID- 2924232 TI - Epidemic of "shocks" in telephone operators: lessons for the medical community. AB - In January 1986 two brief power failures occurring within an hour of each other affected the operation of visual display terminals in a section of the Manitoba Telephone System. After the power failures three operators reported an alarming tingling sensation in their arms and one side of their body, which they called "shocks". Other operators then began to report incidents of numbness and tingling in their limbs, face or head as well as other, diffuse symptoms. During the next 2 weeks 92 such incidents were reported by 55 operators. The media carried alarming headlines, and medical practitioners perpetuated the label of "electric shock". Despite extensive investigation, which revealed no electrical fault, the section was closed by the regulatory authority, and an independent medical panel was convened to review the findings. The panel concluded that there was no immediate hazard to life or health and recommended continued workplace assessment and follow-up of affected operators; however, because the panel lacked electrical engineering expertise, uncertainty persisted as to the cause of the events. The reports of incidents persisted, peaking in association with continued rumours of diagnoses of "nerve damage". In the fall of 1987 a multidisciplinary committee ruled out as causative factors all known hazards other than electrostatic shock and occupational stress. This costly and lengthy investigation underlines the danger in regarding collective stress reaction as a diagnosis of exclusion. It highlights the need to scrutinize objective evidence before validating potentially unfounded concerns and underlines the desirability of considering the psychosocial effects of technology and regimented tasks. PMID- 2924233 TI - Acute pancreatitis associated with HIV infection. PMID- 2924234 TI - Since when did we become experts on delivering health care? PMID- 2924235 TI - Teaching in Fiji: practising medicine, coping with coups. PMID- 2924236 TI - Beyond latex: is AIDS education becoming too explicit? PMID- 2924237 TI - Organized medicine must represent all physicians, CMA forum told. PMID- 2924238 TI - BPP: psychotherapy that takes weeks, not years. PMID- 2924239 TI - The case of the questionable reference. PMID- 2924240 TI - "Why are you going into geriatrics"? PMID- 2924241 TI - Viral exanthems. PMID- 2924242 TI - The 40 year evolution of the first modern day hospital. AB - The first modern psychiatric day hospital founded over 40 years ago has gone through a number of re-organizations which reflect utilization patterns representative of day hospitals in general. The author traces chronologically the dynamic movement from self-contained settings emphasizing group integration to expanded structures providing individualized treatment approaches. The day hospital's unique location at the interface of the institution and the community has important implications for today's mental health policy. PMID- 2924243 TI - Validity of the GHQ-30 in a Nigerian medical outpatient clinic. AB - Basic mental health vital statistics are scarce in developing countries. Scarcer still are validated psychological survey instruments which can be used in these settings. A method of dealing with such scarcity is through the validation of instruments developed elsewhere. One such instrument is Goldberg GHQ-30. The 30 item General Health Questionnaire was used by the authors as a screening instrument for emotional disorder in a general medical outpatient clinic. The GHQ 30 misclassified 32.3% of the respondents, a majority of whom were false positives. There is a tendency for the misclassified respondents to suffer from chronic physical ailments, and to be older. The GHQ-30 appears not to have high specificity (65%) and sensitivity (73%). The predictive value (53.3%) of a positive finding by this screening instrument in this population is also low. Informed consent was obtained from participating subjects. PMID- 2924244 TI - The role of marital intimacy in psychiatric help-seeking. AB - Epidemiological studies have shown that most people with diagnosable psychiatric illnesses do not seek professional help. Symptoms of non-psychotic emotional illness, interpersonal relationship quality and personality traits have demonstrable associations. The influence of these factors on help-seeking was examined by comparing 57 psychiatric outpatients with a community sample of 90 symptomatic individuals on self-report measures of marital intimacy, life events, and personality, while controlling for symptomatology. Compared to non-patients, outpatients reported less intimacy in their marriages across a variety of relationship dimensions on the Waring Intimacy Questionnaire, and scored higher on the Psychoticism scale of the Eysenck Personality Questionnaire. Marital Intimacy level proved to be the best single predictor of patient and non-patient status, suggesting that help-seeking behaviour may be partly motivated by unsatisfactory marriages. The detection of low marital intimacy in these help seekers might be an indication for prescribing marital therapy. PMID- 2924245 TI - Geriatric psychiatry training in Canada: current teaching facilities and resources. AB - A survey of Canadian psychiatry residency programs requested information on training activities in geriatric psychiatry. Fourteen out of sixteen programs responded. On average ten hours of didactic instruction were provided per year over the four years of the residency program. Only one program had no facility that provided a rotation in geriatric psychiatry. The majority of programs have policies that encourage exposure of trainees to the care of the elderly. There is a concentration of teachers of this sub-specialty in a minority of centres. These findings are discussed in the light of current and future needs in the care of the elderly. Recommendations for meeting these are proposed. PMID- 2924246 TI - Psychiatric admission of mentally ill mothers with their infants. AB - There is a greatly increased risk of a woman developing a psychiatric illness requiring hospital admission during the early postpartum period. Admission of the mother has usually meant separating her from her infant at a time when bonding and attachment are developing. Nearly 40 years ago English psychiatrists began admitting infants with their mentally ill mothers, and although the theoretical basis for this is sound, there are few systematic studies of the practical problems encountered, or the outcomes. This paper compares a group of 32 psychiatrically ill postpartum women who were admitted to a Canadian general hospital psychiatric unit with their infants to a group of 26 psychiatrically ill postpartum women hospitalized on the same unit who refused admission of their infants. The women admitted with their infants were more likely to be older, living with the infants' father, in a stable residence and job, in hospital for a longer time, and caring for their babies at 2 year follow-up in contrast to the women who were admitted without their infants. The two groups were diagnostically different with joint admission mothers likely to suffer from an affective psychotic illness, while the mothers without infants were more likely to suffer from personality disorder or substance abuse. The effects of mother-infant admission and some of the practical problems encountered are discussed. PMID- 2924247 TI - Length of stay, short stay units and psychiatric emergency admissions. AB - Length of stay information was collected from 1,364 individuals over a one year period for five general hospitals in a major metropolitan area. The current set of data represents homogeneity in the nature of admissions and the type of facilities examined. Three of the hospitals operated short stay units. Significant differences in the total length of stay were observed according to age, sex and presence of psychosis but there were no unequivocal distinctions between short stay and conventional hospitals. PMID- 2924248 TI - Prediction of regrets in postoperative transsexuals. AB - This study investigated whether heterosexual males are more likely to regret sex reassignment surgery than homosexual males or females. Subjects were 111 postoperative transsexuals who had been surgically reassigned for at least one year, representing a follow-up rate of 84.1%. Subjects' feelings about surgery were assessed with self-administered questionnaires. None of the 61 homosexual females or 36 homosexual males consciously regretted surgery, compared to 4 of the 14 heterosexual males: a significant difference. This finding suggests that heterosexual applicants for sex reassignment should be evaluated with particular caution, although a heterosexual preference is not an absolute contraindication for surgery. PMID- 2924249 TI - Sex differences in the phenomenology of schizophrenic disorder. AB - The content and structure of delusions were compared in 30 women and 30 age matched men with Schizophrenic Disorder. Men showed an excess of homosexual persecutory delusions and of grandiose delusions involving social status and personal power. Women showed an excess of delusions of fertility and of jealousy, and were more often than men objects rather than subjects in their grandiose delusions. There was an excess of women who reported co-objects of persecution, and who personally knew their persecutors, nearly always men. These differences mirrored aspects of the social environment, especially with regard to sex-role stereotyping. PMID- 2924250 TI - The French connection: folie a quatre. AB - A socially isolated family in which the three children shared their mother's delusional beliefs is reported. After separation, the children rapidly adjusted to normal school and foster family life. Difficulties in establishing the family's true identity and problems raised in reuniting the family, while the mother was felt to be concealing her remaining delusions, are discussed. PMID- 2924251 TI - Consent to treat: clinical and legal implications. AB - Procedural requirements under the provisions of the Mental Health Act can delay the implementation of treatment for an involuntary psychiatric patient refusing treatment. The authors present such a case where treatment could not be given for nearly two months during which the patient's condition sharply deteriorated. With treatment, the patient improved within two weeks and was allowed to go home. Considerable time and money was spent in the Regional Review Board hearings. The implications of the case are discussed and it is recommended that steps be taken to prevent the interference of a bureaucratic legal system in the day to day practice of psychiatry. PMID- 2924252 TI - The third special edition on child psychiatry: an overview. PMID- 2924253 TI - Symptom patterns of alcoholism in a northern Ontario population. PMID- 2924254 TI - Predictors of suicide in borderline personality disorder. AB - One hundred patients with borderline personality disorder who were followed for a mean of 15 years were compared with 14 borderline patients who committed suicide. The most significant predictors of completed suicide were previous attempts and higher education. PMID- 2924255 TI - Treatment intensity and outcome for children with acute lymphocytic leukemia of standard risk. A Pediatric Oncology Group Study. AB - Four hundred thirty-four children, with good-risk acute lymphocytic leukemia (ALL), were assigned randomly to receive intensive or less intensive maintenance therapy with 6-mercaptopurine and methotrexate, plus vincristine and prednisone pulses in such a way that patients on treatment 1 had their leukocyte counts maintained between 1500 and 3000/mm3. Patients on treatment 2 had leukocyte counts maintained between 3000 and 4500/mm3. Absolute granulocyte counts were maintained above 500/mm3 on both groups. All children received induction treatment with vincristine, prednisone and L-asparaginase and had central nervous system (CNS) prophylaxis with cranial irradiation and intrathecal methotrexate. The overall remission rate was 94%. Event-free survival at 8 years was 44% (SE, 5.6%). There was no significant difference in outcome between treatments 1 and 2 (P = 0.83). The incidence of infection was similar overall and not significantly different between treatment arms. PMID- 2924256 TI - Long-term results in 144 localized Ewing's sarcoma patients treated with combined therapy. AB - The results of 144 previously untreated cases of primary Ewing's sarcoma of bone are reported with a minimum follow-up of 5 years. This series was treated between 1972 and 1982 at Istituto Ortopedico Rizzoli with a combined therapy. The local control of the disease consisted of amputation (ten cases), resection followed by radiation therapy (35-45 Gy) (48 cases) and radiation therapy alone (40-60 Gy) (86 cases). Adjuvant chemotherapy, rigorously standardized, was performed according two different protocols: the first (85 cases treated in the period 1972 1978) consisted of vincristine (VCR) Adriamycin (doxorubicin) (ADM), and cyclophosphamide (EDX); the second (59 cases treated in the period 1979-1982) of VCR, ADM, EDX and dactinomycin (DACT). At a follow-up of 5 to 16 years (median, 9), 59 patients (41%) are continuously disease-free (CDF), 81 (56%) developed metastatic disease and/or local recurrence, and four (3%) had a second malignancy. Three factors seem to be correlated to prognosis: the site of the initial lesion (only 23% of the pelvic lesions are represented in the CDF group versus 46% of the other locations); the chemotherapy protocol (32% of the cases in the first protocol are CDF versus 54% in the second); the type of local treatment (60% of the patients treated with amputation or resection plus radiotherapy versus 28% of those treated with radiation therapy alone are CDF). A local recurrence was observed in 24% of the patients (8% in the group locally treated with surgery or surgery plus radiation therapy versus 36% in the group treated with radiation therapy alone). These data suggest that even though adjuvant chemotherapy can improve the long-term results in localized Ewing's sarcoma patients, this disease still represents, in a high percentage of cases, a lethal process whose final prognosis widely depends on the local control of the lesion. Due to the questionable effect of the radiation therapy alone in controlling the primary lesion and its important side effects, the role of surgery in treating Ewing's sarcoma of bone should be extended. PMID- 2924257 TI - The correlation of specific variables of tumor differentiation with response rate and survival in patients with advanced head and neck cancer treated with induction chemotherapy. AB - The authors have reported previously that conventionally defined grades of tumor morphology do not correlate with tumor response or survival in advanced squamous cell cancers of the head and neck (SCCHN) treated with cisplatinum combination induction therapy. This lack of correlation may be the result of the imprecision and subjectiveness of the conventional grade determination. To examine this possibility, response and survival were correlated with individual parameters of morphologic differentiation in 136 patients with advanced, untreated SCCHN. A multi-variable analysis of degree of keratinization, number of mitotic figures per high powered field, degree of nuclear differentiation, presence of vascular invasion, intensity of inflammatory response, and invasion pattern of the cancer was performed. The grade of each variable was weighted by assigning a score from 1 to 4, with 1 representing the most differentiated and 4 the least. The cumulative score of each specimen was tallied and assigned to one of three groups, less than 12, 12 to 18, and greater than 18, analogous to the conventional grades of well, moderately, and poorly differentiated, respectively. No correlation between the grade of individual morphologic variables and response to chemotherapy was demonstrated, or between tumor response and cumulative score groups. There was no correlation of the grade of individual morphologic variables or cumulative score groups with survival. Only the survival of patients achieving a complete response to chemotherapy was correlated with the cumulative score groups: 2-year survivals of 84%, 70%, and 46% for less than 12, 12 to 18, and greater than 18, respectively. Multi-parameter analysis of individual features of tumor differentiation is not superior to conventional morphologic analysis in predicting response to chemotherapy or survival in patients with advanced SCCHN. PMID- 2924258 TI - Cytocidal effects of misonidazole, Ro 03-8799, and RSU-1164 on euoxic and hypoxic BP-8 murine sarcoma cells at normal and elevated temperatures. AB - Euoxic and hypoxic BP-8 murine sarcoma cells were exposed for up to 3 hours to various concentrations of three nitroimidazole derivatives (misonidazole, Ro 03 8799, RSU-1164) at normal or elevated incubation temperatures. Cell survival was monitored with the iodine 125 (125I)-iododeoxyuridine prelabeling assay. When cell lethality was evaluated as a function of drug molarity, the three nitroimidazoles displayed widely different toxicities, but when expressed in terms of toxicity ratio between euoxic and hypoxic cells, all three drugs showed nearly identical toxicity differentials of 16 to 18 in 1-hour drug incubation experiments. Prolonging the treatment period to 3 hours did not change the euoxic/hypoxic toxicity ratio for misonidazole and Ro 03-8799, but with RSU-1164 the toxicity ratio was increased significantly from 16 (1 hour) to 73 (3 hours). This increase was attributed to the bifunctional action of RSU-1164 as a combined electron-affinic and alkylating agent, with the alkylation component of cell killing becoming more pronounced after prolonged drug incubation under hypoxic conditions. Combined administration of hyperthermia and nitroimidazoles increased drug-induced cell lethality for all three agents, but did not materially change the relative toxicity differential between euoxic and hypoxic cells. In short, based on cellular toxicity data, Ro 03-8799 appears to offer no advantage over misonidazole as a selective cytocidal agent for hypoxic cells, but RSU-1164 does provide a moderate therapeutic advantage. PMID- 2924259 TI - Intraperitoneal cisplatin chemotherapy versus abdominopelvic irradiation in ovarian carcinoma patients after second-look laparotomy. AB - The current study compares the outcome within 3 years after diagnosis in two groups of histologically confirmed Stage II-IV ovarian carcinoma patients in complete clinical remission with minimal or no residual disease at second-look laparotomy, performed after completion of cisplatin-based combination chemotherapy. One group (n = 18) received after reexploration abdominopelvic irradiation (RT group), the other, diagnosed during a later period (n = 19), received three courses of intraperitoneal cisplatin chemotherapy with systemic thiosulfate protection (IP group). The two groups were comparable with regard to age, stage at diagnosis, histologic category, grade of differentiation, size of residual tumor after the initial operation, and rate of negative second-look laparotomy. The overall survival probability after diagnosis was significantly better in the IP group, the maximal difference being observed at 36 months: 76.6% versus 44.4% in the RT group (P = 0.04). This difference was mainly evident in patients with a negative second-look laparotomy in whom the respective survival probabilities were 100% versus 70% (P = 0.04). Survival was significantly shorter (P less than 0.01) in patients with a positive second-look, and there was a nonsignificant trend for better survival in the IP group. Significantly improved probability of progression-free interval after diagnosis was also found in the IP group, the maximal difference being observed at 22 months: 78.3% as compared to 50.9% in the RT group (P = 0.04). This difference was again limited to patients with negative second-look, the respective values being 100% versus 60% (P = 0.05). Our retrospective data suggest an apparent advantage to intraperitoneal cisplatin treatment in these patients which should be further explored for definite evaluation. PMID- 2924260 TI - Changes in serum levels of Forssman-like antibody in patients with gastric cancer. AB - Because Forssman antigen, one of the most well-known heteroantigens, has been noted in certain cancerous tissues, it would seem that the serum levels of the Forssman antibody of patients with these cancers would be low, owing to the absorption of the naturally occurring antibody by the Forssman antigen-containing cancerous tissues. This hypothesis was tested by researchers assessing the serum hemolysin titers of 174 patients with cancer (gastric cancer, 100; colonic cancer, 40; and other cancers, 45) and of 856 age-matched, sex-matched, and blood type-matched healthy individuals against the serum levels of sheep red blood cells. Serum levels of the hemolysin of patients with gastric cancer tend to be lower than those of patients with other types of cancer and also lower than those of age-matched and sex-matched controls. The decrease was especially prominent in patients with moderately differentiated adenocarcinoma of the stomach. Preoperative and postoperative serum samples of 40 patients with gastric cancer were analyzed therefore to determine the effect of surgically removing the cancer on the serum level of the hemolysin. The results showed that the serum levels of the hemolysin antibody increased in all 40 patients after the successful surgical removal of the cancer. However, in patients with recurrence of the cancer, the serum levels of hemolysin decreased again in 11 of 11 patients. These results indicate that the serum levels of the Forssman-like hemolysin could be used as an index of recurrence in patients with gastric cancer after surgical removal of the cancer. PMID- 2924261 TI - The pathogenesis of splenic extramedullary hematopoiesis in metastatic carcinoma. AB - Splenic extramedullary hematopoiesis (EMH) is a characteristic finding in agnogenic myeloid metaplasia (AMM) and in the spent phase of polycythemia vera (PV). Evidence from our laboratory has suggested that splenic EMH in these conditions results from the filtration of circulating hematopoietic cells from the peripheral blood and does not arise de novo from splenic stem cells. To further test this hypothesis, 31 autopsy and 26 surgical cases of carcinoma metastatic to the bone marrow were studied. The presence of leukoerythroblastosis (LEB) correlated with intravascular hematopoiesis (IVH) in the bone marrows associated with reticulin fibrosis, and with splenic EMH in the autopsy cases. These studies provide evidence that stromal changes in the bone marrow with resulting IVH, LEB, and splenic EMH are not unique to AMM and PV but also occur in such unrelated conditions as metastatic carcinoma, and suggest that these phenomena are causally related. PMID- 2924262 TI - Mesothelioma and asbestos fiber type. Evidence from lung tissue analyses. AB - Lung tissue samples from 78 cases from autopsy of mesothelioma in Canada, 1980 through 1984, and from matched referents were examined by optical and analytical transmission electron microscopic study. Concentrations of amosite, crocidolite, and tremolite fibers, and of typical asbestos bodies discriminated sharply between cases and referents. The distributions of chrysotile and anthophyllite/talc fibers and of all other natural and man-made inorganic fibers (greater than or equal to 8 microns) in the two series were quite similar. Relative risk was related to the concentration of long (greater than or equal to 8 microns) amphibole fibers with no additional information provided by shorter fibers. The proportion of long fibers was much higher for amphiboles than chrysotile and, except for chrysotile, systematically higher in cases than referents. Amphibole asbestos fibers could explain most mesothelioma cases in Canada and other inorganic fibers, including chrysotile, very few. Fibrous tremolite, contaminant of many industrial minerals including chrysotile, probably explained most cases in the Quebec mining region and perhaps 20% elsewhere. PMID- 2924263 TI - The effect of tumor size and tumor cell DNA content on the survival of patients with stage I adenocarcinoma of the lung. AB - Tumor size at resection and flow cytometric (FCM) DNA distribution of 93 pathologically confirmed AJC Stage I adenocarcinomas of lung were compared with survival. All lung cancers had been treated by lobectomy and mediastinal lymph node dissection at this Institution, and the pathology of all cases was reviewed. Median tumor size was 2.5 cm. FCM DNA assays were carried out on the formalin fixed, paraffin-embedded tumor tissue. Seventy-nine (85%) of the tumors were aneuploid and 14 were diploid. There was no significant difference in survival between patients with diploid and aneuploid tumors. The DNA index, proliferation fraction, and fraction of aneuploid cells also had no effect on survival. However, patients with tumors smaller than 3 cm in diameter had a significantly better prognosis than those with larger tumors. Thus, in Stage I adenocarcinoma of lung, tumor size but not cellular DNA content distinguishes subgroups with favorable versus unfavorable prognosis. PMID- 2924264 TI - Increased mucosal ornithine decarboxylase activity in large bowel with multiple tumors, adenocarcinoma, and adenoma. AB - The polyamine biosynthetase, ornithine decarboxylase (ODC), involved in tumor promotion, was investigated in grossly normal mucosa obtained from surgically resected large bowel; 48 cases with and six cases without large bowel cancer. The mucosal ODC activity was significantly higher in 17 multiple tumor cases bearing adenocarcinoma(s) plus adenoma(s) than in 31 solitary tumor cases bearing one adenocarcinoma alone. It was higher in the mucosa of the two groups of cases than in the mucosa of individuals without large bowel cancer. Furthermore, the enzyme activity in left-sided cancer cases was significantly higher than that in right sided cancer cases. Carcinoma tissue showed a remarkable high level of enzyme activity, compared with the normal mucosa. The results indicate the larger the number of tumors the higher the level of the ODC activity in the normal mucosa, particularly in left-sided cancer cases. It is concluded that the mucosal ODC may provide a good biological marker to detect individuals at higher risk for large bowel cancer due to exogenous or endogenous factors, and thus contribute to the prevention of mortality from large bowel cancer. PMID- 2924265 TI - Mucin profiles and potential for malignancy of human colorectal adenomatous polyps. AB - The mucin histochemical and histologic features of 166 colorectal adenomatous polyps from 124 patients were studied. A majority of the polyps (62%) had a tubular growth pattern whereas 38% showed villous growth. Severe dysplasia was more frequently found in the latter group. A significant correlation (r = 0.27, P less than 0.001) was found between the severity of dysplasia and the size of the polyps. Moreover, the ratio between goblet and columnar cells was also found to decrease (P less than 0.0001) with the severity of dysplasia. Independent of the mucin stain used (periodic acid-Schiff, alcian blue, and high-iron diamine stains), mucin reactive cells were found to be negatively correlated (-0.17 less than r less than -0.44, P less than 0.01) with severity of dysplasia, especially in the tubular adenomas. These findings suggest that evaluation of mucin stain, related to dysplasia, may contribute to the assessment of premalignant and early malignant changes in adenomas of the colon. PMID- 2924266 TI - Check samples for laboratory self-assessment in DNA flow cytometry. The National Cancer Institute's Flow Cytometry Network experience. AB - The National Cancer Institute's Flow Cytometry Network (NCI-FCN) is attempting to facilitate the transfer of flow cytometry (FCM) of exfoliated bladder cells from the research laboratory to the clinical laboratory. Demonstrating interinstitutional consistency in FCM analysis of replicate specimens simulating clinical barbotage specimens, fixed to allow easy transportation and storage at room temperature was one specific objective. Simulated barbotage specimens were prepared by mixing cultured aneuploid bladder carcinoma cells with normal or mitogen-stimulated peripheral blood mononuclear cells in different ratios. The samples were fixed in 10% formalin for 30 minutes, stored in buffer, and enucleated with pepsin, pH 1.5, before staining with propidium iodide for FCM DNA analysis. Preservation in ethanol or other common DNA cytochemical reagents was found to be unsatisfactory. In contrast, the formalin-fixed samples showed excellent preservation of quantitative DNA fluorescence and coefficient of variation of histogram peaks for over 2 weeks. Exchange of eight fixed specimens among five network laboratories that analyzed them as "unknowns" showed good overall agreement on histogram data and interpretation, although some noteworthy interlaboratory differences were found. This technique could be used for self assessment surveys of clinical laboratory performance in DNA FCM of bladder barbotage specimens. PMID- 2924267 TI - Genitourinary rhabdomyosarcoma in children. AB - Although rhabdomyosarcoma of the genitourinary tract occurs infrequently in children, it presents a challenging problem to the surgeon, radiotherapist, and oncologist. Thirty-six children with genitourinary rhabdomyosarcoma were treated at our institutions from 1957 to 1985. The primary site of tumor involved the bladder, prostate, or both in 15 patients, the paratesticular structures in 12, and female reproductive organs in nine. Although treatment modalities and philosophies of care varied over the past 27 years, the majority of patients were treated with a combination of surgery, chemotherapy, and radiation therapy. The event-free survival for all patients is 74%. Patients with paratesticular tumors had the best prognosis (88% event-free survival). Regional nodal radiation therapy is not necessary in this favorable group if the retroperitoneal lymph node dissection is negative. Of 15 children with bladder/prostate tumors nine had initial conservative surgery. Of these nine six are long-term survivors, but only three patients have intact bladders. The girls with tumors of the reproductive organs had an event-free survival of 63%; all patients in this group had hysterectomies. Chemotherapy and radiotherapy have not substituted for radical surgical procedures in most children with bladder or prostate rhabdomyosarcomas. Innovative therapeutic approaches are necessary for this group of patients. PMID- 2924268 TI - Risk of second malignancy after cutaneous T-cell lymphoma. AB - Risk of second primary malignancy was assessed in a population-based follow-up survey of all persons who developed cutaneous T-cell lymphoma (CTCL) in nine geographic areas of the United States covered by the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute during the period 1973 to 1983. Among 544 patients with a first primary tumor reported as CTCL, a second cancer developed in 35 (6%), yielding a significantly elevated relative risk (RR) of 1.7, which reflects excesses for cancers of the lung and colon and non-Hodgkin's lymphoma. Although the excess of lymphoma may be related to the evolution of CTCL to less differentiated T-cell lymphoma, additional studies are needed to clarify the immunologic, genetic, viral, and environmental factors that may contribute to the development of second cancers. PMID- 2924269 TI - Breast involvement with acute lymphocytic leukemia. PMID- 2924270 TI - Angioimmunoblastic lymphadenopathy. Review of 44 patients with emphasis on prognostic behavior. AB - In order to investigate the relationship between histologic findings and clinical behavior in angioimmunoblastic lymphadenopathy (AILD), 44 patients with AILD were reviewed. These patients comprised 24 men and 20 women with age range from 25 to 84 years of age (median, 64 years). Lymphadenopathy was observed in all patients, systemic in 37, and localized in seven. Polyclonal hypergammaglobulinemia was present in 64% of patients. Histologically clear cells or convoluted cells were observed in 36% and 48% of the patients, respectively. Univariate analysis (log rank test) for prognostic factors revealed age, appetite, presence of clear cells, or convoluted cells were important factors. However, multivariate analysis revealed that there were no independent factors for prognosis. The presence of clear cells and/or convoluted cells were histologic signs for poor prognosis; autopsy showed that patients with the clear cells with or without convoluted cells mostly died of active disease of AILD with two cases progressing to non Hodgkin's lymphomas and those with convoluted cells alone died of lung infection. From these findings, AILD could be divided into three groups: AILD with (1) clear cells with or without convoluted cells, (2) convoluted cells alone, or (3) neither cells. The first two groups showed poor prognosis, and the last a favorable prognosis. PMID- 2924271 TI - Psychosexual adaptation to breast cancer surgery. AB - Disturbances associated with a breast cancer diagnosis were defined when psychological assessments from 63 patients with a known breast cancer diagnosis were compared to those from 56 patients with an as yet undiagnosed malignancy. Subsequent assessments from the 56 patients with an undiagnosed breast cancer showed disturbances after they saw a physician compared with the assessments from 72 similar patients ultimately diagnosed as benign. Apprehension apparently arose from clues given before a biopsy was done even though the cancer was not yet diagnosed. Compared with the benign breast disease group, the disturbances in patients suspected or diagnosed with breast cancer were found chiefly in assessments of mood and adjustment, and less in assessments of more durable characteristics of personality, psychopathology, and sexual behavior. Psychological problems associated with breast cancer decreased over time, but residuals persisted for at least 16 months postoperatively. Few differences were found between 41 patients who elected breast-conserving surgery and 78 who were treated with mastectomy. Problems were not eliminated by operations which saved the breast. PMID- 2924272 TI - Safer sex guidelines. PMID- 2924273 TI - Unconventional student, unconventional approach. PMID- 2924274 TI - Implementing a non-restraint philosophy. PMID- 2924275 TI - Community and professional empowerment. PMID- 2924276 TI - McMaster's link with Pakistan. PMID- 2924277 TI - Nursing the hearing impaired patient. PMID- 2924278 TI - [Anger]. AB - Anger is universal, its variations in the human species well documented. Under certain conditions, it can even work in our favor. Here, the author examines how we manage anger, its positive and negative aspects, as well as its manifestations -biological and in the form of bodily expressions. Through intellectualizing our anger, she says, we rationalize it. Yet when we act solely out of emotion, we increase our vulnerability. The author suggests appropriate means of expressing our anger and of accepting the anger of dying patients. PMID- 2924279 TI - [Helping the family of the schizophrenic patient]. AB - The authors, nurses who run a day program out of Centre hospitalier Ste-Therese de Shawinigan to help friends or families of schizophrenic patients, explore what makes the service so successful. Called Centre Info-Famille-Contact-Schizo, it was the brainstorm of psychiatrist Dr. Pierre Lalonde, who maintains that such families need information and support; after all, they are true allies of the patient. PMID- 2924280 TI - Diversity in biomedical imaging. PMID- 2924281 TI - Designing a flexible user interface for both users and programmers. AB - The design of a user interface for computers is examined from both the end user's and the programmer's point of view. Different methods of menu selection and user feedback are discussed. A graphics interface using pull down menus and dialog boxes is ideal for simplifying user interaction and program organization. This style of interface also provides for a modular program development environment, reduced program development time, program portability, and reduced maintenance. Software tools for programming the user interface are explored and pseudo-code examples are given. PMID- 2924282 TI - Database management in autoradiography. AB - Experiments in autoradiography involve the use of radiotracers to achieve a "functional mapping" between structures of the central nervous system and observed behavior in animals. A typical experiment produces 100-300 sections per animal. Computer systems such as DUMAS (Drexel's Unix based iMage Analysis System) are used to analyze these sections. Each section has two images associated with it--an autoradiographic image and a histological image. The latter is used to establish a correlation between anatomical structures and areas on the autoradiogram. User drawn outlines on the histological image are transferred to the autoradiographic image to obtain quantitative measures (such as average gray level). Existing systems do not take advantage of the fact that consecutive sections obtained from a brain are often similar. As a result, much of the effort involved with region outlining is repetitive. Also, the criteria for region selection varies not only across experiments, but also between users. This paper presents an approach to design an integrated database management system to manage both pictorial and quantitative data in autoradiography. Briefly, such a system is used to (a) store sets of reference outlines and images for use during the analysis of sections, (b) provide a bank of information to the user from across experiments, (c) provide an on-line help facility to the novice, and a reference guide to the expert. Based on specific requirements, we chose the relational model for data management. We developed a preliminary version of the database using INFORMIX-ESQL/C, which is a commercially available relational system. We also developed a graphics editor that is actively linked to the database. The results of our efforts have established the feasibility of using a commercially available relational system for autoradiographic data management. PMID- 2924283 TI - Skin cancer recognition by computer vision. AB - Automatic detection of several features characteristic of basal cell epitheliomas is described. The features selected for this feasibility study are semitranslucency, telangiectasia, ulcer, crust, and tumor border. Image processing methods used in this study include frequency analysis of the Fourier transform of the image, the Sun-Wee texture analysis algorithm, and several other image analysis techniques suitable for skin photographs. This image analysis software is designed for use with AI/DERM, an expert system that models diagnosis of skin tumors by dermatologists. PMID- 2924284 TI - Multiple spectral parameter imaging in quantitative fluorescence microscopy. I: Quantitation of bead standards. AB - Digitized images from fluorescence microscopy may suffer from nonlinearity of camera response to illumination intensity, from uneven spatial response of the camera, and from uneven illumination of the microscopical field. Structureless fluorescence standard slides are used to characterize the camera response. This information permits the images to be corrected for all the above errors, in one operation. The computer algorithms are described, and also those for thresholding and finding objects. The method is illustrated by tests using fluorescent beads. PMID- 2924285 TI - Modulation of flavocoenzyme levels in rat tissues by N-nitrosodiethylamine. AB - The hepatocarcinogen N-nitrosodiethylamine (NDEA) was administered continuously in drinking water (200 mg/l) to male Wistar rats, and at intervals tissues were examined for flavocoenzyme levels. Flavin adenine dinucleotide (FAD) and non-FAD riboflavin were determined fluorimetrically. Results revealed significant depletion in hepatic levels of these compounds at the end of 60 days, a period of exposure considered adequate for the development of hepatoma. Considerable reduction was also noticed after 15 days, and also when lower dose of NDEA was administered (50 mg/l). The flavin compounds in liver after short exposure to NDEA remained at depleted levels even after withdrawal of the carcinogen. Changes in the kidney were found to be less significant. The selective depletion of flavin compounds in the target tissue following NDEA exposure is of significance, and may be related to biochemical mechanisms involved in malignant transformation. PMID- 2924286 TI - Selective fractionation of hypoxic B16 melanoma cells by density gradient centrifugation. AB - Cells of the mouse B16 melanoma growing in monolayer culture and as tumors were fractionated by isopycnic density centrifugation in a linear-density (1.02-1.20 g/ml) metrizamide gradient. Cultured cells concentrated into one or two distinct bands, with densities of 1.02-1.04 g/ml and 1.06-1.10 g/ml, depending on growth conditions. Cells subjected to extreme hypoxia (less than 0.02% O2) banded predominantly at the lower density, and normally-oxygenated cells banded at the higher density. Fractionated tumor cells concentrated at both densities. Compared with cells at the higher density, lower-density cells incorporated more of the hypoxic cell radiosensitizer [14C]misonidazole and less [3H]thymidine in vivo, were less clonogenic but more resistant to X-irradiation in situ, and labeled to a lesser extent with intravenously-delivered Hoechst 33342 fluorochrome, a marker for cells proximal to tumor blood vessels. Lower-density tumor cells were, therefore, enriched in non-proliferating radioresistant hypoxic cells from tumor regions remote from blood vessels. PMID- 2924287 TI - Identification in rats of N-nitrosonipecotic acid as a major urinary metabolite of the areca-nut alkaloid-derived nitrosamines, N-nitrosoguvacoline and N nitrosoguvacine. AB - N-Nitrosamines derived from areca-nut alkaloids have been implicated in cancer of the oral cavity and esophagus caused by betel quid chewing in India and other Asian countries. A major urinary metabolite of N-nitrosoguvacoline and N nitrosoguvacine, both present in saliva of betel quid chewers of ppb levels, was isolated from rat urine and identified as N-nitrosonipecotic acid by comparison with the authentic compound. When a dose of 50 or 500 micrograms/rat of either compound was administered orally to BDIV rats, 66-85% of the dose was excreted in the urine as N-nitrosonipecotic acid and 2-8% as N-nitrosoguvacine. These N nitrosamino acids could be analysed in the urine of betel quid chewers as a marker of exposure to areca-nut specific nitrosamines. PMID- 2924288 TI - Effects of a triazine antifolate (NSC 127755) on serine hydroxymethyltransferase in myeloma cells in culture. AB - The effect of the triazine antifolate NSC 127755 on serine hydroxymethyltransferase activity in mouse myeloma X63 cells in culture was determined. The enzyme was inhibited, apparently irreversibly, with IC50 approximately 5 X 10(-8) M. A similar concentration-dependency for inhibition of [6-3H]deoxyuridine incorporation into DNA was observed in these cells in culture. Long-term culture of myeloma cells with NSC 127755 resulted in a progressive decrease in the number of viable cells. The study emphasises the significance of serine hydroxymethyltransferase as a target for anticancer chemotherapy. PMID- 2924289 TI - Long-term carcinogenicity of cyclophosphamide in two mouse strains with different spontaneous leukemia incidence. AB - The aim of the present study was to investigate to what extent the induction of leukemia by the carcinogenic agent cyclophosphamide (CPA) might be influenced by the genetic predisposition. CPA was s.c. administered at 26 mg/kg and 13 mg/kg weekly for lifetime to AKR mice which are genetically predisposed to develop leukemias, and to NMRI mice, that exhibit a low spontaneous leukemia rate. CPA dose-dependently increased the median life span in AKR mice by 27% and 76% (P less than 0.001), and decreased the incidence in leukemias by 17% and 37% (P less than 0.01), respectively. In NMRI mice, CPA significantly increased the incidence of leukemias by 46% at the low dose (P less than 0.02) and 26% at the high dose (P less than 0.03), respectively. The apparently parallel observations of the lower leukemia incidences following the higher CPA-dosage in both strains probably are related to different mechanisms of action: in the susceptible, genetically determined AKR mice the therapeutic effect of CPA prevailed its carcinogenic potential and the genetic host factors whereas in the resistant NMRI mice the cytotoxic efficacy of CPA reduced its carcinogenicity at the higher dosage. PMID- 2924290 TI - Identification of a human homologue of the murine tumor rejection antigen GP96. AB - A family of cell surface glycoproteins with a molecular weight of 96,000 (gp96) has recently been implicated in the individually distinct immunogenicity of chemically induced sarcomas of inbred mice. Rabbit antiserum to murine gp96 detects an antigenically related Mr 96,000 cell surface glycoprotein on two cultured human melanoma cell lines, SK-MEL-13 and SK-MEL-177. Molecular probes for 5' and 3' ends of the murine gp96 gene detect a 3.5-kilobase transcript in RNA preparations from melanoma cells, similar to the murine gp96 transcript. While 5' probes do not hybridize to Southern blots of genomic human DNA, the 3' probes identify several distinct bands under stringent hybridization and washing conditions. This suggests that the 3' end of the gp96 gene is more conserved than its 5' end. No gross alterations in gp96 gene organization were detected in melanoma cells. B-lymphoblastoid cell lines derived from four different individuals also showed no restriction fragment polymorphism in the gp96 gene. PMID- 2924291 TI - Tubulin-dependent hydrolysis of guanosine triphosphate as a screening test to identify new antitubulin compounds with potential as antimitotic agents: application to carbamates of aromatic amines. AB - Tubulin-dependent GTP hydrolysis was evaluated for its potential as a relatively simple screening assay for new antimitotic drugs. Carbamates of aromatic amines were chosen as the test system because of the relatively diverse structures of compounds in this class already known to have antimitotic properties and because of the large number of such compounds in the NSC collection of the National Cancer Institute. Of 162 compounds evaluated, significant alterations in the GTPase reaction were observed with 26 agents. Sixteen of these had substantial inhibitory effects on tubulin polymerization (true positives), while ten did not (false positives). There were no false negatives (i.e., no agent inactive in the GTPase assay inhibited tubulin polymerization). The true positives were examined for effects on cell growth and mitosis, and four compounds had 50% inhibitory concentration values of 2 microM or less with L1210 murine leukemia cells. All four caused the accumulation of cells in metaphase arrest. We conclude that tubulin-dependent GTP hydrolysis can be used effectively to select new antitubulin compounds with potential as antimitotic agents from a large group of compounds of unknown activity. PMID- 2924292 TI - Characterization of a malignant phenotype-associated cell surface glycoprotein common to various human tumor cells and preferentially expressed on adenocarcinoma of the lung. AB - Since both the liver and lung are derived from the endoderm, common antigens may appear on both tissues during malignant transformation. In an attempt to delineate cell surface alterations associated with the neoplastic transformation of these tissues, we have produced a library of monoclonal antibodies against a human hepatoma cell line termed FOCUS. One of these monoclonal antibodies, designated AF-10, recognized an antigen preferentially expressed on human lung adenocarcinoma cells, both in vitro and in vivo. This antigen has been characterized using Western immunoblot analysis and immunoprecipitation from surface-iodinated or metabolically labeled cells. The mature antigen is a cell surface glycoprotein with a core polypeptide with a molecular weight of 75,000 bearing N-glycosylation units. This protein migrates in sodium dodecyl sulfate polyacrylamide gel electrophoresis with an apparent molecular weight of 100,000 115,000 in reducing conditions and Mr 115,000-130,000 in nonreducing conditions. The epitope recognized by monoclonal antibody AF-10 is borne by the core protein. This antigen is shed from the cell surface and was identified in the culture supernatant from lung adenocarcinoma cell lines. Studies of the biodistribution of the AF-10 antigen showed that it was also expressed at low levels in normal human small intestine and kidney. The AF-10 monoclonal antibody may be useful for the study of the antigen expression between normal lung and the transformed phenotype. PMID- 2924293 TI - Incidence of serum antibody reactivity to autologous head and neck cancer cell lines and augmentation of antibody reactivity following acid dissociation and ultrafiltration. AB - Serum antibody reactivity to squamous cell carcinoma of the head and neck (SCCHN) was evaluated in 41 autologous serum-tumor cell line combinations using the protein A hemadsorption assay. Autologous antibody reactivity (median titer of 1:4) was detected in sera from 24 of the patients tested. In 10 cases autologous antibody reactivity could be detected only in undiluted serum precluding further analysis. Analysis of higher titer sera from one patient revealed antibodies that define an antigen expressed on autologous tumor cells cultured from both the primary tumor (UM-SCC-17A) and from a metastasis (UM-SCC-17B). Absorption analysis showed that this antigen was also expressed on 6 of 10 allogeneic SCCHN cell lines but not on autologous fibroblasts or on allogeneic melanoma cell lines. Due to the low titer of autologous antibody reactivity in most sera, we sought to determine if dissociation of immune complexes through acidification and ultrafiltration of serum might enhance detectable antibody reactivity as has been done in previous studies in melanoma. Twelve serum samples from eight patients were subjected to acid dissociation and ultrafiltration (AD-U). Only six of the untreated sera had detectable antibody reactivity against the autologous SCCHN cell line whereas following AD-U all 12 sera had enhanced IgG reactivity against autologous SCCHN. Specificity analysis of one serum sample after dissociation revealed that the antibody detected an antigen common to SCCHN cell lines as well as melanoma, glioma, renal, and colon carcinoma cell lines. Circulating immune complexes may provide a reservoir of antibody with potential diagnostic and therapeutic applications. PMID- 2924294 TI - Effect of androgen on proliferation of estrogen-responsive transformed mouse Leydig cells in serum-free culture. AB - We examined the effects of steroid hormones on the proliferation of transformed mouse Leydig cells (B-1) in serum-free culture condition. Among hormones examined, androgen as well as estrogen enhanced the cell proliferation rate. Hormone binding studies revealed that B-1 cells contained both androgen and estrogen receptors. In addition, androgen-enhanced cell growth was inhibited by antiandrogen, but not by antiestrogen, while estrogen-stimulated cell growth was suppressed by antiestrogen. However, the simultaneous addition of androgen and estrogen did not show an additive effect. Dose-response study on androgen dependent cell growth revealed that relatively high concentrations (10(-7)-10(-6) M) of dihydrotestosterone were required to obtain the maximum response. This was at least partly explained by the finding that B-1 cells could metabolize dihydrotestosterone into the less active steroids. Finally, B-1 cells were found to grow more rapidly in normal than in castrated male mice. These results clearly indicate that the proliferation of B-1 cells is stimulated by both androgen and estrogen, which utilize the different receptor systems. PMID- 2924295 TI - 1-beta-D-arabinofuranosylcytosine and hydroxyurea production of cytotoxic synergy with cis-diamminedichloroplatinum(II) and modification of platinum-induced DNA interstrand cross-linking. AB - 1-beta-D-Arabinofuranosylcytosine (ara-C) and hydroxyurea (HU) were investigated as possible inhibitors for the repair of cis-diamminedichloroplatinum(II) (DDP) induced DNA damage. HU and ara-C were chosen for their known ability to inhibit DNA excision repair following UV irradiation. Work by several groups has suggested that the repair of DDP-induced DNA damage may involve an excision repair mechanism. The cytotoxic effects of dose, exposure duration, and sequence for the three drugs was studied in a human colon cancer cell line (HT-29) by colony formation assays. Significant synergistic cytotoxicity was seen whether HU + ara-C were given prior to, or following DDP exposure. Cytotoxic synergy was also seen between HU + ara-C themselves. The effect of the combined antimetabolites on the level and persistence of DDP-induced DNA interstrand cross links was assessed by DNA alkaline elution. These were measured as an indicator of DDP-DNA adduct formation and removal. When HU + ara-C exposure preceded or followed DDP treatment, higher levels of interstrand cross-linking were found at late time points than were seen with DDP alone, suggesting repair inhibition. We conclude that the combination of HU, ara-C, and DDP shows synergistic cytotoxicity, and that this effect may be due in part to inhibition of DDP induced DNA adduct repair. The concentrations of drugs used in vitro are achievable in humans. On the basis of these results, a Phase I/II clinical trial of the three agents in combination has been initiated. PMID- 2924296 TI - Deletion mapping in human renal cell carcinoma. AB - The highest incidence of renal cell carcinoma (RCC) is reported in Scandinavia. Cytogenetic studies of constitutional tissue in families with hereditary RCC and of sporadic RCC tumor tissue have shown abnormalities of chromosome 3p. In a study of 23 sporadic Scandinavian cases using restriction fragment length polymorphism analysis, we found that 68% of informative patients showed terminal 3p deletions. The break point was not consistent. Loss of a locus on the Y chromosome was seen in 4/14 male patients. Losses of heterozygosity on autosomes included chromosomes 18 (5/15 informative cases) and 17 (3/11 informative cases). Losses in heterozygosity were also found at lower levels for other chromosomes (chromosome 13, 3/16; chromosome 10, 2/19; and chromosome 11, 2/24). The single familial case showed reduplication of part of chromosome 3p and of one chromosome 17. Our data confirm earlier data on losses on chromosome 3p in tumor tissue and by extending this type of analysis to all chromosomes, demonstrate the specificity of this loss. No unique findings were made in the sporadic Scandinavian cases. The results support the thesis that a tumor suppressor gene involved in the oncogenesis of RCC may be located distal to the DNF15S2 locus on chromosome 3p. PMID- 2924297 TI - Rapid reduction of tetrachloro(D,L-trans)1,2-diaminocyclohexaneplatinum(IV) (tetraplatin) in RPMI 1640 tissue culture medium. AB - Tetrachloro(D,L-trans)1,2-diaminocyclohexaneplatinum(IV) (tetraplatin) is a new platinum analogue which is less nephrotoxic than cisplatin and is effective in some cell lines which have become resistant to cisplatin. Since platinum(IV) compounds are thought to require reduction to their platinum(II) analogues for activity, the biotransformations of tetraplatin and its platinum(II) analogue, dichloro(D,L-trans)1,2-diaminocyclohexaneplatinum(II) [PtCl2(trans-dach)], were studied. For L1210 cells cultured in RPMI 1640 medium, the time course for inhibition of DNA synthesis and cytotoxicity was virtually identical for both drugs. The time course for binding to fetal calf serum in the tissue culture medium was also the same for both drugs. In the complete tissue culture medium, tetraplatin was reduced to PtCl2(trans-dach) with a half-life of 5 to 15 min, depending on the level of protein sulfhydryl in the medium. The major reducing agent in the medium was the protein sulfhydryl, with glutathione and glucose making minor contributions. No other component of the medium reacted with tetraplatin. The rapid reduction of tetraplatin to PtCl2(trans-dach) was followed by much slower substitution reactions involving the chloro ligands of PtCl2(trans dach). The major transformation products which accumulated in RPMI 1640 medium were identical for both drugs. These data suggest that tetraplatin should be considered a prodrug which is very rapidly converted to PtCl2(trans-dach) with subsequent biotransformations as expected for the platinum(II) analogue. These data also indicate that in tissue culture most of the tetraplatin is reduced extracellularly. PMID- 2924298 TI - Competitive inhibition by verapamil of ATP-dependent high affinity vincristine binding to the plasma membrane of multidrug-resistant K562 cells without calcium ion involvement. AB - Verapamil, a calcium channel blocker, can inhibit the efflux of antitumor agents from multidrug-resistant cells and reverse drug resistance. We have recently reported that the plasma membrane prepared from an adriamycin (ADM)-resistant variant (K562/ADM) of human myelogenous leukemia K562 cells showed ATP/Mg2+ dependent high affinity binding of vincristine (VCR), which is closely related to the drug transport mechanism in this cell line. To clarify how calcium channel blockers inhibit the transport of antitumor agents from the resistant cells, we analyzed the effect of calcium channel blockers and Ca2+ ion on the VCR binding to K562/ADM plasma membrane. The ATP-dependent VCR binding was inhibited by calcium channel blockers (verapamil, nicardipine, and diltiazem), which are known to inhibit drug efflux from the resistant cells. Addition of [ethylenebis(oxyethylenenitrilo)]tetraacetic acid or high concentration of Ca2+ decreased the amount of VCR binding to some extent; however, a substantial amount of VCR still could bind to K562/ADM plasma membrane. The inhibitory effect of verapamil on the VCR binding was observed regardless of the Ca2+ concentration. Klotz plot analysis revealed that the inhibition of the VCR binding to K562/ADM plasma membrane by verapamil was competitive. Dissociation constant (Kd) of VCR and apparent inhibitory constant (Kiapp) of verapamil were calculated to be 0.1 +/- 0.1 microM (SD) and 1 +/- 1 microM, respectively. These results indicate that Ca2+ ion is not required for the VCR binding and that verapamil competitively inhibits the VCR binding without concerning Ca2+ ion. Antitumor agents (vinblastine, actinomycin D, ADM, and colchicine) and other agents known to reverse multidrug resistance (nicardipine, diltiazem, cyclosporin A, quinidine, and trifluoperazine) also inhibited the VCR binding competitively. PMID- 2924299 TI - Slowing of cell cycle traverse for cells in exponential monolayer cultures placed into plateau-fed and starved medium. AB - MCa-11 tumor cells in exponential monolayer cultures were pulse/chase-labeled with [3H]thymidine and then regrown in fresh, plateau-fed, or starved medium. We measured the DNA content and autoradiographic labeling of these cells by absorption cytophotometry at intervals of 0, 2, 4, 8, 12, and 24 h to follow the progress through the cell cycle of those cells which had incorporated isotope. We found that for the cells grown in plateau-fed and starved medium the G0/G1, S, and G2 phases of the cell cycle were prolonged when compared to those for cells grown in fresh medium. These results show that, under adverse microenvironmental conditions, the growth of tumor cells can be regulated in all phases of the cell cycle, and that this regulation can include lengthening and even cessation of replicative DNA synthesis. PMID- 2924300 TI - Substrate specificity and alkyl group selectivity in the metabolism of N nitrosodialkylamines. AB - Metabolic activation may be a key step in determining the tissue specificity of carcinogenic nitrosamines. In previous work, we characterized P450IIE1 (an acetone/ethanol-inducible form of cytochrome P-450) as the major enzyme for the metabolic activation of N-nitrosodimethylamine. In this work, we investigated the metabolism of other N-nitrosodialkylamines in rat liver microsomes and in reconstituted monooxygenase systems containing purified cytochrome P-450 isozymes. The enzyme specificities in the metabolism of N-nitrosoethylmethylamine and N-nitrosodiethylamine were similar to those of N-nitrosodimethylamine; i.e., these substrates were more efficiently metabolized by acetone- or ethanol-induced microsomes than by other types of microsomes. However, substituting one methyl group with a benzyl or butyl group, as in N-nitrosobenzylmethylamine or N nitrosobutylmethylamine (NBMA), substantially changed the enzyme specificity. P450IIE1 efficiently catalyzed the demethylation but not the debutylation of NBMA, whereas P450IIB1 (a phenobarbital-inducible form) efficiently catalyzed both the debutylation and demethylation reactions. In the demethylation of NBMA by P450IIE1, the addition of cytochrome b5 markedly increased the activity at low but not at high substrate concentrations, suggesting a decrease in Km value. This effect, however, was not observed in the debutylation of NBMA by P450IIE1 or P450IIB1, and in the demethylation of NBMA by P450IIB1. These studies demonstrate the substrate specificity and alkyl group selectivity in the metabolism of nitrosamines by cytochrome P-450 isozymes. PMID- 2924301 TI - Changes in activities of free radical detoxifying enzymes in kidneys of male Syrian hamsters treated with estradiol. AB - Target organ-specific estrogen-induced DNA adducts were previously shown to precede renal carcinogenesis in Syrian hamsters. Because estrogens induced these DNA modifications, but were not part of the adduct structure, free radical activation of endogenous electrophiles was postulated as a mechanism of tumor induction by estrogens. In the present study, the activities of enzymes which detoxify reactive intermediates were studied in liver and kidney of hamsters treated with estradiol for 1, 2, and 4 mo and in untreated controls. These studies were done to detect oxidative stress in the target organ of carcinogenesis. In the estrogen-exposed hamster kidney (1, 2, and 4 mo), activities of glutathione peroxidases I and II were significantly increased. The activity of catalase was decreased compared to those in untreated controls. In livers which are not the target organ of carcinogenesis, treatment of hamsters with estrogen for 1, 2, and 4 mo resulted in changes of activities of glutathione peroxidases I and II and catalase, which were opposite to the pattern found in the kidney. Activities of superoxide dismutase, glutathione reductase, glucose-6 phosphate dehydrogenase, gamma-glutamyl transpeptidase, and glutathione transferase in estradiol-treated hamster liver and kidney did not differ significantly from those in either liver or kidney of untreated age-matched controls. Fluorescent products of lipid peroxidation more than doubled in the kidney, but not in the liver of hamsters treated with estradiol for 1 mo. It is concluded that the increases in glutathione, in the activity of glutathione peroxidase, and in products of lipid peroxidation in the kidneys of hamsters treated chronically with estrogen all point towards elevated levels of oxidative stress. PMID- 2924302 TI - A monoclonal antibody which identifies the autophosphorylation domain of autophosphorylating protein kinase 500. AB - Autophosphorylating protein kinase 500 is a serine protein kinase expressed progressively with the steps of cellular transformation, approaching levels from 50- to 100-fold in the terminal stages of malignancy. The enzyme possesses a sharply restricted range of substrates: itself and a ribosomal protein with a molecular weight of 31,000 (S6). We report here on the characterization of a monoclonal antibody directed against the autophosphorylation domain of AUT-PK 500. The specificity of the antibody is evidenced by blockage of the enzyme phosphorylation without interfering with the native S6 or synthetic octapeptide (S6-1) serine residue phosphorylations. This represents an important step in identifying a probe that can be used to explore the structure and potential function of AUT-PK 500 in cellular transformation. PMID- 2924303 TI - Effects of 5-hydroxymethyluracil and 3-aminobenzamide on the repair and toxicity of 5-hydroxymethyl-2'-deoxyuridine in mammalian cells. AB - 5-Hydroxymethyl-2'-deoxyuridine (HmdUrd), a cytotoxic analogue of thymidine, has been proposed for use as an anticancer agent. HmdUrd is incorporated into DNA and then removed at a rate of 30-40% per day. The removal of HmdUrd from DNA has been attributed to the action of 5-hydroxymethyluracil-DNA glycosylase (HmUra-DNA glycosylase). We demonstrated the release of [3H]HmUra into the growth medium of V79 Chinese hamster cells that had incorporated [3H]HmdUrd into their DNA. The amount of [3H]HmUra recovered from the growth medium was equal to the amount of [3H]HmdUrd lost from DNA. These experiments confirmed that the initial step of repair of HmUra in DNA was mediated by DNA glycosylase activity. A combination of HmUra and HmdUrd resulted in increased uptake of HmdUrd by cells and increased cytotoxicity. The increased incorporation of HmdUrd into DNA was not due to inhibition of repair. 3-Aminobenzamide, an inhibitor of poly(ADP-ribose) synthesis, was cytotoxic to cells which incorporated and repaired HmdUrd. The extent of toxicity was directly related to the number of HmUra residues in DNA. HeLa cells, known to be resistant to the toxic effects of HmdUrd, do not incorporate HmdUrd into their DNA. HeLa cells were resistant to the toxic effects of 3-aminobenzamide, confirming that the absence of HmdUrd in their DNA was not due to an accelerated rate of repair. These experiments indicate that the potential therapeutic antineoplastic properties of HmdUrd may be enhanced by using HmUra to increase the incorporation of HmdUrd into DNA and 3-aminobenzamide to interfere with repair of HmUra in DNA. PMID- 2924304 TI - Effect on growth and cell cycle kinetics of estradiol and tamoxifen on MCF-7 human breast cancer cells grown in vitro and in nude mice. AB - The effects of estradiol and tamoxifen (TAM) on the estrogen-dependent human breast cancer cell line MCF-7 grown in vitro and in nude mice were compared. The effect on growth was determined by cell number in vitro and by tumor growth curves in nude mice. The effects on the cell cycle kinetics were determined by repeated flow cytometric DNA analyses in vitro and in vivo and by the technique of labeled mitosis in nude mouse-grown tumors. Under in vitro conditions, estradiol induced a pronounced increase in S-phase fraction and cell number. TAM inhibited growth of MCF-7 cells with a concomitant increase in the G1 phase from 60% to 75%. In nude mice, MCF-7 only formed tumors in estradiol-supplemented mice. No differences were observed in growth and cell kinetics between 0.1 and 1.0 mg of estradiol. Daily i.p. injections of TAM resulted in tumor growth inhibition with shrinkage of tumors. The flow cytometric DNA analysis and percentage of labeled mitosis investigations revealed no significant differences in the proliferation kinetics of TAM-treated and control tumors. Calculating the cell loss factor demonstrated an increase from 69% in control tumors to 107% in TAM-treated tumors. These experiments have shown that the cell kinetic effect of TAM is different when MCF-7 cells are grown in vitro versus in vivo. In contrast to the in vitro data, the in vivo data indicate that the growth-inhibitory effect of TAM is not mediated through a perturbation of the cell cycle. PMID- 2924305 TI - Morphological and cytokinetic responses of hamster airways to intralaryngeal or intratracheal cannulation with instillation of saline or ferric oxide particles in saline. AB - The morphological and proliferative effects of intratracheal cannulation (ITC) or intralaryngeal cannulation (ILC), with or without the instillation of saline or Fe2O3 particles in saline, were studied in Syrian golden hamsters. Instillation of Fe2O3 in saline at either airway level resulted in a similar distribution of Fe2O3 particles in all lung lobes. ILC produced laryngeal mucosal wounds. ITC produced laryngeal and tracheal mucosal wounds. The cannula-induced wounds were associated with proliferative epithelial lesions. ITC, but not ILC, resulted in significant increases in the mitotic rates (MR, 6-h colchicine blockade) of tracheal epithelial cells at 24 and 32 h postcannulation. Instillation of saline by ITC produced slight increases in intrapulmonary bronchial and bronchiolar MR, but saline given by ILC did not increase MR at any airway level. Instillation of Fe2O3 particles in saline by ITC produced increases in tracheal, intrapulmonary bronchial, and bronchiolar MR. Instillation of Fe2O3 particles in saline by ILC had little effect on tracheal MR, but increased intrapulmonary bronchial and bronchiolar MR. Foci of Fe2O3 particle-laden macrophages were associated with mild bronchiolar-alveolar hyperplasia at the junctions of the terminal bronchioles and the alveolar ducts. The cytokinetic and morphological changes in the intrapulmonary airways were associated with the influx of inflammatory cells in response to Fe2O3 particle deposition. The marked increases in tracheal MR and the localized hyperplastic tracheal epithelial lesions were clearly associated with mechanical wounding from the cannula during ITC. Comparative studies using ILC or ITC instillation techniques allowed further investigations of the important role of tracheal mucosal wounding in the induction of respiratory carcinogenesis, as described in a companion paper (Keenan et al., Cancer Res., 49: 1528-1540, 1989). PMID- 2924306 TI - Multifactorial hamster respiratory carcinogenesis with interdependent effects of cannula-induced mucosal wounding, saline, ferric oxide, benzo[a]pyrene and N methyl-N-nitrosourea. AB - The carcinogenic response induced in the respiratory tract of Syrian golden hamsters by repeated intratracheal instillations of benzo[a]pyrene (BP) adsorbed to ferric oxide (Fe2O3) particles suspended in saline, is shown to result from the interactions of these factors and cannula-induced tracheal wounding. Previous acute studies of intratracheal cannulation (ITC) versus intralaryngeal cannulation (ILC) showed that tracheal cell proliferation increased significantly in ITC-induced mucosal wounds. Only mild increases in intrapulmonary cell proliferation were produced by Fe2O3-saline given by ILC or ITC (Keenan et al., Cancer Res., 49: 1521-1527, 1989). The present chronic studies included the following variables: a single instillation by ILC of N-methyl-N-nitrosourea (MNU) at 5 weeks of age; 15 weekly treatments (beginning at 7 weeks of age) by ILC or ITC alone, or with instillations of saline, or Fe2O3-saline, or BP-Fe2O3-saline; and appropriate controls. Repeated ITC-induced tracheal wounds caused persistent tracheal epithelial hyperplasia, metaplasia and/or atrophy and submucosal fibroplasia during the observation period of 22 to 78 weeks of age (the time of terminal sacrifice). Tracheal cancers (in situ or invasive carcinomas) were seen only in those hamsters which had received repeated ITC and one or both carcinogens. The cancer latency was shortest and the incidence of tracheal (50%) and main-stem bronchial (21%) cancers highest in hamsters given MNU and repeated ITC with BP-Fe2O3-saline. Hamsters given carcinogens by ILC (which induced laryngeal but not tracheal wounds) developed proliferative lesions and cancers of the larynx but no tracheobronchial cancers. These data show the singular importance of repeated ITC-induced intratracheal wounding as an enhancing factor in this respiratory carcinogenesis model. The findings suggest that the mechanism of tumor enhancement involves not only changes in target epithelial cell proliferation, but also alterations in normal epithelial-mesenchymal interactions during tracheal regeneration from repeated chronic submucosal inflammation and mesenchymal repair. In the present experimental model, a single dose of MNU at 5 weeks of age, repeated instilled doses of BP, and tracheal mucosal wounding were each found to be important determinants of the carcinogenic response. Additional effects were observed for instilled Fe2O3 particles, and possibly saline. Interplay of all these factors, as well as of genetic, nutritional, and infectious factors, are considered in relation to risk assessment and prevention. PMID- 2924307 TI - Induction of osteosarcomas in mouse lumbar vertebrae by repeated external beta irradiation. AB - Besides skin tumors, osteosarcomas were induced at high frequency in the lumbar vertebrae of ICR mice by repeated local external irradiation of the back with 90Sr-90Y beta-rays when irradiation was repeated three times a week until tumors appeared. The optimum dose range for osteosarcoma induction was 250-350 cGy per exposure at the surface of the back, or 125-175 cGy at the depth of the center of the bone. With the same irradiation schedule, the optimal dose of radiation for induction of osteosarcomas was much lower than that for induction of skin tumors. PMID- 2924308 TI - Enhanced activity of peritoneal cells after aclacinomycin injection: effect of pretreatment with superoxide dismutase on aclacinomycin-induced cytological alterations and antitumoral activity. AB - Peritoneal macrophages from mice injected with aclacinomycin (ACM) (4 mg/kg, i.p.) showed increased functional activity, as assessed by increased antitumoral activity in vitro and in vivo and zymosan-triggered chemoluminescence. They also showed ultrastructural signs of activation (increased number of cytoplasmic organelles), and atypical alterations (giant vacuoles and giant lysosomes containing heterogenous myelinoid bodies, lipofuscine-like substance, cytoplasmic debris, and a fine granular material). As these atypical alterations could be due to the generation of superoxide following ACM injection, superoxide dismutase (SOD) was injected 1 h prior to ACM administration. Neither the morphological characteristics of activation, nor the enhanced metabolic and antitumoral activities induced by ACM were affected by SOD pretreatment, but the atypical alterations were inhibited in a dose-dependent manner. Heat-inactivated SOD did not prevent their appearance. The atypical alterations were not found in peritoneal macrophages from talc or lipopolysaccharide-injected mice, but they were present in Adriamycin-treated mice and were also prevented by SOD pretreatment, indicating that the alterations are due to anthracycline treatment. Finally, [125I]SOD was phagocytized by peritoneal macrophages in vitro and in vivo and not by L1210 tumoral cells, explaining why the atypical alterations induced by ACM were no longer seen after SOD pretreatment. The unchanged direct oncostatic activity of ACM following SOD pretreatment suggests that this combination may have some wider perhaps clinical, potential. PMID- 2924309 TI - Effect of specific antibody pretreatment on liver uptake of 111In-labeled anticarcinoembryonic antigen monoclonal antibody in nude mice bearing human colon cancer xenografts. AB - Administration of a large dose (0.2 mg) of unlabeled specific anticarcinoembryonic antigen (anti-CEA) monoclonal antibody (MAB) to nude mice bearing LS174T human colon cancer xenografts significantly decreased normal liver uptake of 111In-labeled anti-CEA MAB (Indacea). Mice bearing tumors of approximately 1 g showed liver accumulation of indium-111 at 48 h following injection of 2 micrograms/10 microCi Indacea of 33.8 +/- 1.5% injected dose per gram (%ID/g) (N = 25). Treatment with 0.2 mg unlabeled anti-CEA MAB reduced this to 8.9 +/- 0.5% ID/g (N = 22; P less than 0.001). The dose of pretreatment was found to be critical. Increasing the amount of unlabeled MAB to 2.0 mg did not significantly improve the liver level of indium-111, but did compromise the tumor uptake of Indacea (15.9 +/- 1.3 versus 12.4 +/- 0.4% ID/g; P less than 0.05). Lowering the dose of pretreatment 10-fold resulted in increased (P less than 0.001) liver uptake of the label (26.5 +/- 2.8% ID/g). The unlabeled anti-CEA MAB treatment given as a single dose or fractionated over several days gave the same results. The decrease in liver uptake was the same for i.v. administration of the unlabeled MAB given 1 week prior to Indacea injection or mixed together with Indacea. With i.p. administration, simultaneous injection of the unlabeled MAB with Indacea was not as effective as pretreatment (20 min to 7 days) in decreasing the liver uptake of 111In (P less than 0.05). Epitope specificity and affinity were shown to be important considerations in the choice of MAB combinations used for pretreatment and imaging. Pretreatment with nonspecific MAB was ineffective in decreasing liver uptake of Indacea. PMID- 2924310 TI - Stomach cancer among New Mexico's American Indians, Hispanic whites, and non Hispanic whites. AB - Stomach cancer incidence rates vary by ethnic group in New Mexico, with American Indians and Hispanic Whites at higher risk than the state's non-Hispanic White population. To further characterize the descriptive epidemiology of this disease in New Mexico, we investigated temporal trends in stomach cancer mortality and incidence rates. Stomach cancer mortality rates declined over a 25-year period (1958-1982) among New Mexico's Hispanic and non-Hispanic Whites. Birth cohort analysis suggests that much of the decline was achieved prior to 1968. Stomach cancer mortality rates did not drop among American Indians during the same period. Stomach cancer incidence rates remained constant for Hispanic Whites, non Hispanic Whites, and American Indian males over a 13-year period (1969-1982), but more than doubled among American Indian females. Although environmental factors have been implicated in the etiology of stomach cancer, little is currently known about the distribution of such risk factors among the ethnic groups described in this report. The environmental and biological correlates of sex, ethnicity, and socioeconomic status that determine stomach cancer risk merit further investigation in New Mexico. PMID- 2924311 TI - Combination of N-methylformamide with cis-diamminedichloroplatinum (II) in murine mammary carcinoma: importance of timing. AB - The maturational agent N-methylformamide (NMF) is an antitumor agent that also enhances the response of tumor cells in vitro to chemotherapeutic agents. Here, we tested whether NMF can improve therapy of the murine MCA-K mammary carcinoma with cis-diamminedichloroplatinum(II) (cis-DDP). Although the in vitro cell cultures of MCA-K tumor cells exhibited increased sensitivity to cis-DDP cytotoxicity when they were first treated with NMF, administration of NMF to mice bearing MCA-K tumors did not enhance cis-DDP-induced tumor growth delay. However, when NMF treatment was begun after cis-DDP administration, the growth delays were significantly greater than those induced by the individual treatment, with an increase in temporary tumor regression and a small proportion of cures. These results indicate that therapeutic benefit can be achieved in this experimental tumor system when NMF is administered after cis-DDP. In addition, they demonstrate the significance of the timing of administration in combined protocols involving NMF. PMID- 2924312 TI - Oxidative damage in murine tumor cells treated in vitro by recombinant human tumor necrosis factor. AB - Treatment of three murine tumor cell lines, L929, P388, and Pan-02, in vitro with recombinant human tumor necrosis factor (rhTNF) produced evidence of oxidative damage as measured by (a) increases in intracellular glutathione levels, (b) the formation of intracellular oxidized glutathione and (c) the formation of thymine glycols in DNA. L929, the most sensitive of the three cell lines to the cytotoxic activity of rhTNF, had the lowest total glutathione content and was observed to have the highest levels of oxidized glutathione and thymine glycol formation. In addition, the radical buffering capacity of these cells was significantly compromised within 7 h of treatment with rhTNF. The P388 and Pan-02 cell lines, with total glutathione levels about 50-fold higher than L929, also showed evidence of oxidative attack, although to a lesser extent than L929. The radical buffering capacity of these cell lines was not altered by rhTNF treatment. A rhTNF-resistant subline of L929 (L929r), produced by successive passaging in vitro in the presence of TNF, increased its glutathione and oxidized glutathione levels in response to a subsequent rhTNF challenge. Meth A, a cell line resistant to rhTNF in vitro but not in vivo, showed no evidence of oxidative damage following rhTNF treatment, despite having a low radical scavenging capacity and a sensitivity to H2O2. The results with Meth A suggest that the interaction of rhTNF with this cell line does not occur in the same manner as the other cell lines, perhaps due to receptor differences or to some type of "uncoupling" of the signal-response network between the TNF receptor and a putative secondary messenger(s). These results are consistent with the hypothesis that: (a) the mechanism of action of rhTNF involves the production of oxidative damage, including damage to the DNA; (b) the sensitivity to rhTNF in vitro is related to the radical scavenging capacity of the cell; and (c) cells can respond to rhTNF challenge by increasing their free radical scavenging capacity. PMID- 2924313 TI - Proliferative activity in the colon of the mouse and its modulation by dietary starch, fat, and cellulose. AB - The effect of dietary starch, fat, and cellulose on colonic proliferation was studied in female C57Bl/6J mice after 4 weeks of feeding with diets containing various levels of starch (3, 36, and 57-65%), various levels of fat (corn oil, 5 and 29%) and various levels of cellulose (2 and 10%). Cell proliferation was measured by colchicine arrest and [3H]thymidine incorporation. The following parameters were analyzed: mitotic index, labeling index, and position of labelled cells along the crypt. Increasing starch content from 3 to 36% decreased cell proliferation both in low (5%) and high (29%) fat diets. By estimating simultaneously the effects of starch and fat with a single multiple regression model, we observed a decrease of mitotic index from 3.04 +/- 0.34 to 2.04 +/- 0.43 (means +/- SE) (P less than 0.05) when starch was increased from 3 to 36% regardless of the level of fat. Other proliferation parameters showed a similar pattern. Changes in dietary fat alone did not affect significantly cell proliferation. We also investigated the effect of starch at high levels (57-65%) and its interactions with cellulose. High starch (57-65%) increased the labeling index from 7.70 +/- 0.58 to 9.65 +/- 0.88 (P less than 0.05), when also considering the effect of cellulose in the multiple regression model. Cellulose by itself did not change the labeling index. Varying starch from 36 to 57-65% increased the number of cells/crypt column from 22.20 +/- 0.82 to 25.87 +/- 1.21 (P less than 0.05) and varying cellulose from 2 to 10% increased the number of cells/crypt column from 22.20 +/- 0.82 to 27.25 +/- 0.97 (P less than 0.01). The results indicate that either high or low fat diets, containing 36% starch, have the minimum proliferative effects in the mouse colon. However, diets containing high levels of both starch (57%) and cellulose (10%) may induce an increase in proliferation. These data suggest a potential beneficial effect of starch on colon proliferation. PMID- 2924314 TI - Effect of cyclophosphamide on the immature rat ovary. AB - To investigate the early ovarian changes after cyclophosphamide treatment, immature rats primed for 48 h with pregnant mare serum gonadotropin were given injections i.p. of cyclophosphamide (100 mg/kg) at 1, 2, 4, 16, and 24 h before decapitation. Serum estradiol dropped significantly after 24 h of exposure to cyclophosphamide (P less than 0.001). Following 16 and 24 h of cyclophosphamide exposure, (a) the number of granulosa cells expressed from each ovary decreased (P less than 0.05 and P less than 0.01, respectively); (b) the number of nucleated bone marrow cells decreased (P less than 0.01 and P less than 0.01), and their median nuclear size was significantly reduced (P less than 0.05 and P less than 0.05) as measured by Coulter Counter and C-256 channelyzer (Hialeah, FL); and (c) the mean follicular diameter and the number of follicles with diameters greater than 300 microns were significantly lower than in control. After 4, 16, and 24 h of exposure, median granulosa cell nuclear size significantly increased (P less than 0.05, P less than 0.01, and P less than 0.01, respectively). DNA cross-links in granulosa cells, measured by alkaline elution, reached a maximum at 2 h of exposure and decreased thereafter. The above findings demonstrate that cyclophosphamide has significant effects on the rat ovary structure and function and that the granulosa cell is an important target of cyclophosphamide-induced ovarian toxicity. PMID- 2924315 TI - Human monoclonal antibodies reactive with human myelomonocytic leukemia cells. AB - Peripheral blood mononuclear cells from a patient with chronic myelogenous leukemia (CML), in remission, were depleted of CD8-positive T-cells and cultured with Epstein-Barr virus. Four of 20 cultures (20%) secreted human IgG antibodies selectively reactive with the cell surfaces of certain human leukemia cell lines. Three polyclonal, Epstein-Barr virus-transformed, B-cell lines were expanded and fused with the human-mouse myeloma analogue HMMA2.11TG/O. Antibody from secreting clones HL 1.2 (IgG1), HL 2.1 (IgG3), and HL 3.1 (IgG1) have been characterized. All three react with HL-60 (promyelocytic), RWLeu4 (CML promyelocytic), and U937 (monocytic), but not with KG-1 (myeloblastic) or K562 (CML erythroid). There is no reactivity with T-cell lines, Burkitt's cell lines, pre-B-leukemia cell lines, or an undifferentiated CML cell line, BV173. Leukemic cells from two of seven patients with acute myelogenous leukemia and one of five with acute lymphocytic leukemia react with all three antibodies. Normal lymphocytes, monocytes, polymorphonuclear cells, red blood cells, bone marrow cells, and platelets do not react. Samples from patients with other diverse hematopoietic malignancies showed no reactivity. Immunoprecipitations suggest that the reactive antigen(s) is a lactoperoxidase iodinatable series of cell surface proteins with molecular weights of 42,000-54,000 and a noniodinatable protein with a molecular weight of 82,000. Based on these data these human monoclonal antibodies appear to react with myelomonocytic leukemic cells and may detect a leukemia-specific antigen or a highly restricted differentiation antigen. PMID- 2924316 TI - In vivo circumvention of vincristine resistance in mice with P388 leukemia using a novel compound, AHC-52. AB - A novel compound partially analogous to nifedipine, AHC-52, was found to sensitize multidrug-resistant tumor cells. AHC-52 at 0.5 microgram/ml completely reversed the in vitro resistance to vincristine (VCR) in VCR-resistant P388 cells (P388/VCR). Of various regimens examined for the in vivo treatment of P388/VCR bearing mice, the combination of 0.05 mg/kg of VCR with 100 mg/kg twice a day of AHC-52 daily demonstrated the best result with a 206% increase in life prolongation. This result was comparable with that observed in parental P388 bearing mice treated with the optimal dose of VCR alone, indicating almost complete circumvention of resistance by combination VCR-AHC-52 therapy. In addition, the combination of both agents exhibited therapeutic effects in the treatment of P388-bearing mice with some long term survivors. This result was presumably due to the elimination of heterogeneity of VCR sensitivity in this cell population. These results suggest that combination chemotherapy using a sensitizing agent such as AHC-52 will be effective in not only circumvention of multidrug resistance but also retardation of its occurrence. PMID- 2924317 TI - Characterization and biodistribution of recombinant and recombinant/chimeric constructs of monoclonal antibody B72.3. AB - B72.3 is a murine monoclonal antibody (IgG1) that recognizes a tumor-associated glycoprotein, termed TAG-72. B72.3 has been shown, using a variety of methodologies, to have a high degree of selective reactivity for colorectal, ovarian, lung, and breast carcinomas. Radiolabeled B72.3 has been administered both i.v. and i.p. in patients with colorectal and ovarian cancer as well as other carcinomas and has been shown to selectively bind to approximately 70-80% of metastatic lesions. Greater than 50% of the patients that have been treated with B72.3 have developed an immunological response to murine IgG after a single injection. In an attempt to minimize the immune response of these patients to the administered murine monoclonal antibody, we developed a recombinant form of the murine B72.3 as well as a recombinant/chimeric antibody, using the variable regions of the murine B72.3 and human heavy chain (gamma 4) and light chain (kappa) constant regions. We report here that both the recombinant B72.3 [rB72.3] and the recombinant/chimeric B72.3 [cB72.3(gamma 4)] IgGs maintain the tissue binding and idiotypic specificity of the native murine IgG. The native B72.3, rB72.3, and cB72.3(gamma 4) IgGs were radiolabeled and the biodistribution of these IgGs was studied in athymic mice bearing human colon carcinoma xenografts (LS-174T). Differences were observed between the cB72.3(gamma 4) and the native B72.3 in the percentage of injected dose/g that localized in the tumor. The somewhat lower absolute amounts of the cB72.3(gamma 4) in the tumor are mostly likely due to the observed more rapid clearance from the blood and body of the mouse as compared to the native B72.3 and rB72.3. All three forms [native B72.3, rB72.3, and cB72.3(gamma 4)] of the IgG, however, were able to localize the colon tumor with similar radiolocalization indices [percentage of injected dose/g in tumor divided by the percentage of injected dose/g in normal tissue]. PMID- 2924318 TI - Pharmacokinetics of internally labeled monoclonal antibodies as a gold standard: comparison of biodistribution of 75Se-, 111In-, and 125I-labeled monoclonal antibodies in osteogenic sarcoma xenografts in nude mice. AB - In order to know the true biodistribution of anti-tumor monoclonal antibodies, three monoclonal antibodies (OST6, OST7, and OST15) against human osteosarcoma and control antibody were internally labeled with 75Se by incubating [75Se]methionine and hybridoma cells. 75Se-labeled monoclonal antibodies were evaluated both in vitro and in vivo using the human osteogenic sarcoma cell line KT005, and the results were compared with those of 125I- and 111In-labeled antibodies. 75Se-, 125I- and 111In-labeled monoclonal antibodies had identical binding activities to KT005 cells, and the immunoreactivity was in the decreasing order of OST6, OST7, and OST15. On the contrary, in vivo tumor uptake (% injected dose/g) of 75Se- and 125I-labeled antibodies assessed using nude mice bearing human osteosarcoma KT005 was in the order of OST7, OST6, and OST15. In the case of 111In, the order was OST6, OST7, and OST15. High liver uptake was similarly seen with 75Se- and 111In-labeled antibodies, whereas 125I-labeled antibodies showed the lowest tumor and liver uptake. These data indicate that tumor targeting of antibody conjugates are not always predictable from cell binding studies due to the difference of blood clearance of labeled antibodies. Furthermore, biodistribution of both 111In- and 125I-labeled antibodies are not identical with internally labeled antibody. Admitting that internally labeled antibody is a "gold standard" of biodistribution of monoclonal antibody, high liver uptake of 111In-radiolabeled antibodies may be inherent to antibodies. Little, if any, increase in tumor-to-normal tissue ratios of antibody conjugates will be expected compared to those of 111In-labeled antibodies if stably coupled conjugates are administered i.v. PMID- 2924319 TI - Increased thermal response to ultrasound in the Walker carcinosarcoma treated with vasoactive drugs. AB - In order to evaluate the potential of a highly selective Ca2+ entry blocker (nisoldipine) and of 5-hydroxytryptamine (5-HT) as adjuvant in hyperthermia treatment, we studied the differential flow response and time-course of tumor and normal tissue temperature following the administration of the two substances and during ultrasound heating. In 12 rats bearing Walker 256 carcinomas i.p. injection of 0.2-0.4 mg/kg nisoldipine caused a reduction in the tumor-to-muscle flow relationship of 4.4 +/- 1.9 (SD) to 1.74 +/- 0.86 as determined by intraarterial 133Xe injection; i.p. injection of 2-8 mg/kg 5-HT (N = 13) caused a respective reduction from 3.9 +/- 2.67 to 1.3 +/- 1.59. During a 20-min period of 41 degrees C normal tissue temperature-controlled ultrasound heating without drugs, tumor temperature attained 40.8 +/- 0.9 degrees C (N = 16). Nisoldipine or 5-HT injection at continuing 41 degrees C normal tissue temperature controlled energy delivery produced an instantaneous further increment of tumor temperature, eventually to 44.0 +/- 1.14 degrees C or 44.2 +/- 1.26 degrees C, respectively, after a period of 20 min. Injection of 0.9% NaCl (N = 4) solution caused only insignificant changes. Blood pressure and muscle perfusion were distinctly influenced by nisoldipine, but not by 5-HT. Since both drugs instantaneously increased the temperature differential between tumor and normal tissue, though by different vasoaction, they should be considered as adjuvants in hyperthermia. PMID- 2924320 TI - Sex differences in the single-dose toxicokinetics of N-nitrosomethyl(2 hydroxyethyl)amine in the rat. AB - The single-dose toxicokinetics of N-nitrosomethyl(2-hydroxyethyl)amine (NMHA) has been characterized in 8-week-old Fischer 344 rats by analysis using high performance liquid chromatography of serial blood samples. An i.v. bolus dose of 0.6 mumol/kg to male rats revealed biphasic first-order elimination with a terminal half-life of 37.4 +/- 1.7 min for unchanged NMHA and 101 +/- 6 min for total radioactivity, and extensive conversion to polar metabolites was seen in the high-performance liquid chromatographic assays. The systemic blood clearance and apparent steady-state volume of distribution for unchanged NMHA were 13.1 +/- 0.9 ml/min/kg, and 685 +/- 31 ml/kg, respectively. Renal blood clearance and intrinsic hepatic clearance were estimated to be 0.805 +/- 0.024 and 16.7 +/- 2.1 ml/min/kg, respectively. A similar dose given to female rats yielded a terminal half-life for NMHA of 27.2 +/- 1.2 min, a steady-state volume of distribution of 652 +/- 23 ml/kg, and systemic blood, renal blood, and intrinsic hepatic clearances of 16.9 +/- 1.3, 1.45 +/- 0.14, and 22.5 +/- 0.3 ml/min/kg, respectively. The sex differences in terminal half-life and systemic blood, renal blood, and intrinsic hepatic clearances were significant at the P less than 0.05 level. Larger doses given by gavage, which appeared to be completely absorbed from the gut, indicated systemic bioavailabilities for unchanged NMHA of 78 +/- 10% and 69 +/- 1% for male and female rats, respectively. Binding of NMHA to plasma proteins was found to be negligible. Taken together the data allow for the conclusion that the observed sex differences in toxicokinetic parameters are due to differences in the intrinsic hepatic clearance of the compound. This difference in the ability of the liver to metabolize NMHA in vivo correlates with and may contribute to the greater susceptibility of female rats to hepatocarcinogenesis and of male rats to development of tumors in the nasal epithelium following oral exposure to NMHA. PMID- 2924321 TI - N-myc amplification and neuronal differentiation in human primitive neuroectodermal tumors of the central nervous system. AB - Despite the phenotypic similarities between primitive neuroectodermal tumors of the central nervous system, childhood neuroblastoma, and peripheral neuroepithelioma, a histogenetic relationship among these neoplasms has not been shown. High levels of N-myc expression occur selectively in developing brain and in some embryonic tumors of neural origin. N-myc amplification and high levels of N-myc expression in childhood neuroblastoma have been correlated with disease stage and prognosis. To determine whether the copy number of the N-myc gene in primitive neuroectodermal tumors of the central nervous system is altered, we examined 20 primitive neuroectodermal tumors by Southern and/or slot blot hybridization to a 1-kilobase N-myc genomic DNA sequence and a 492-base pair N myc-specific subclone as well as to a 1.1-kilobase albumin complementary DNA sequence as a control for gene copy number. Amplification of the N-myc gene was detected in two cerebellar tumors both of which exhibited neuronal differentiation by light microscopy. These tumors had not been treated previously. Of the remaining 18 tumors, eight were undifferentiated, three showed early neuroblastic, and seven focal glial differentiation. These findings suggest a possible relationship between N-myc amplification and neuronal differentiation. PMID- 2924322 TI - Immortalization of normal human kidney epithelial cells by nickel(II). AB - The occupational and environmental hazards of nickel exposure are of great concern in environmental medicine. Nickel workers have increased risk of cancer of the nose, lung, larynx, and possibly the kidney. In the present investigation we have studied the effects of nickel ions on fetal human kidney cortex explants. The explants were continuously exposed to 5 micrograms/ml NiSO4. After 70-100 days in culture foci of phenotypically altered cells appeared. Immortalized cell lines were established and demonstrated to be of human epithelial origin. Tumorigenicity was not induced, but the cells demonstrated decreased requirement for serum, increased plating efficiency and saturation density, and formation of colonies in soft agar. Chromosome changes in the treated cells were observed. Worth mentioning are change in ploidy (3n) and abnormalities of chromosomes 1, 7, 9, 11, 13, 14 and 20; increased numbers of chromosome 17; and loss of normal chromosomes 20 and 22. PMID- 2924323 TI - A prospective study of demographics, diet, and prostate cancer among men of Japanese ancestry in Hawaii. AB - Prostate cancer incidence was prospectively studied among 7999 men of Japanese ancestry who were first examined between 1965 and 1968 and then followed through 1986. During this surveillance period, 174 incident cases of prostate cancer were recorded. Prostate cancer was not associated with any measure of socioeconomic status, including amount of education, type of occupation, and type of residence. There was also no relationship with the number of children, as a surrogate measure of sexual activity. Increased consumption of rice and tofu were both associated with a decreased risk of prostate cancer, while consumption of seaweeds was associated with an increased risk of prostate cancer. There was no relationship between prostate cancer and the intake of various nutrients, including total fat and total protein. Etiological implications of these associations are discussed, but more research is needed on these dietary factors and the subsequent development of prostate cancer before any firm conclusions can be drawn. PMID- 2924324 TI - Lung cancer in women and type of dwelling in relation to radon exposure. AB - A case-control study based on interviews with 210 incident female lung cancer patients, 209 age-matched population controls, and 191 hospital controls was carried out in Stockholm county, Sweden. Radon measurements made in a sample of 303 dwellings, in which the study subjects had lived, showed that dwellings with ground contact had an average concentration of approximately 160 Bqm-3, twice the average concentration of other dwellings. A cumulated radon exposure index was calculated for each subject based on data from the interviews and the measurements. For the total group of lung cancer a relative risk (RR), adjusted for smoking, age, and degree of urbanization, of 1.8 (95% confidence interval: 1.2-2.9) and 1.7 (0.9-3.3) associated with "intermediate" and "high" exposure to radon was found. There was also a significant trend to a positive dose-response relationship (Ptrend = 0.03). For small cell cancer the corresponding figures for RRs were 1.9 (0.6-4.5) and 4.7 (1.5-14.2), respectively (Ptrend = 0.01). There seemed to be a positive interaction between radon exposure and smoking in relation to lung cancer. The findings indicate that domestic radon may be of importance for the induction of lung cancer, particularly for some histological types. PMID- 2924325 TI - Methotrexate and dipyridamole combination chemotherapy based upon inhibition of nucleoside salvage in humans. AB - We have carried out a clinical trial in 23 patients to determine whether dipyridamole modulates the clinical effect of methotrexate. This trial was based upon in vitro studies which indicate that dipyridamole potentiates the cytotoxic action of methotrexate through inhibition of thymidine salvage. Methotrexate was given as a bolus injection 24 h after initiation of a high dose dipyridamole infusion. The trial was designed so that methotrexate was escalated in individuals until toxicity occurred and then the methotrexate dose resulting in toxicity was repeated without dipyridamole. During the course of this study the methotrexate dose was escalated from 10 to 130 mg/m2. While individual patient tolerance varied, moderate to severe myelosuppression and/or mucositis occurred frequently in patients receiving the combination with methotrexate doses greater than or equal to 60 mg/m2. Ten of 10 patients who experienced moderate or severe toxicity with the combination had significantly less toxicity when treated with methotrexate alone. Dipyridamole did not increase toxicity by an alteration in methotrexate elimination. The potentiation of methotrexate by dipyridamole in these patients suggests that physiological thymidine levels are sufficient to perturb the clinical effects of methotrexate and that thymidine salvage may represent a mechanism for clinical resistance to methotrexate. These results also suggest that a high dose dipyridamole regimen can be used as a pharmacological approach to test the role of nucleoside membrane flux on the clinical action of other standard chemotherapeutic drugs. Phase II studies testing the clinical efficacy of this combination should use a methotrexate dose of 60 mg/m2 with a provision for methotrexate dose escalation based upon individual patient tolerance. PMID- 2924326 TI - Noninvasive monitoring of drug biodistribution and metabolism: studies with intraarterial Pt-195m-cisplatin in humans. AB - We have performed a comparative evaluation of systemic (i.v.) and intraarterial (i.a.) cisplatin by using a trace dose of the radiolabeled form of this drug [( 195mPt]cisplatin) to monitor the drug's biodistribution by dynamic scintigraphic imaging. We have analyzed the drug's metabolism using a compartmental model both following i.a. and i.v. administration in patients with gliomas. Significantly larger amounts of radioactivity (up to 10 times higher than in the uninvolved brain) were measured in tumors following i.a. administration, whereas the differential localization following i.v. drug administration was, at best, only twofold that of the uninvolved brain. On the other hand, no significant differences could be detected in the pharmacokinetics of either free cisplatin or platinated proteins in blood. The washout slope in tumors following i.a. administration may be an indicator of the higher local concentration of free cisplatin; no such washout could be observed in tumors following i.v. administration. The present noninvasive methods may help document the amount and the rate of (active) drug deposition at the desired target site. They may also assist in monitoring, prospectively and/or, on line, the probable effect of chemotherapy in an individual patient. In turn it may lead to novel methods for optimizing chemotherapeutic effectiveness at specific tumor-bearing sites and in defined treatment protocols. PMID- 2924327 TI - Effect of tamoxifen on plasma insulin-like growth factor I in patients with breast cancer. AB - Human breast cancer cells secrete and have membrane receptors for insulin-like growth factor I (IGF-I), a growth hormone-dependent peptide that stimulates cell replication. However, little is known about plasma concentrations of IGF-I in breast cancer patients. Plasma IGF-I levels are decreased in malnutrition, decline with advancing age, and are influenced by estrogen. We evaluated the effect of the antiestrogen agent tamoxifen on plasma IGF-I in 32 ambulatory breast cancer patients. Treatment with tamoxifen was associated with lower concentrations of plasma IGF-I (0.48 +/- 0.3 unit/ml in treated versus 1.03 +/- 0.6 units/ml in nontreated patients, P less than 0.01). However, patients treated with tamoxifen did not differ from nontreated patients in age, menopause, duration since diagnosis, metastatic disease, recent weight loss, or measures of nutritional status. We conclude that tamoxifen therapy results in a reduction of plasma IGF-I concentration. We speculate that the antitumor action of tamoxifen in breast cancer is due in part to suppression of IGF-I. PMID- 2924328 TI - Amino-terminal propeptide of type III procollagen: a new prognosis indicator in human ovarian cancer. AB - To investigate the clinical usefulness of the amino-terminal propeptide of type III procollagen (PIIINP) as an indicator of ovarian cancer behavior, 30 patients with advanced epithelial malignancy were monitored with serial serum PIIINP and CA-125 determinations before and during treatment. Initially, PIIINP and CA-125 concentrations were each separately increased in 87% of the cases and, simultaneously, in 77% of the cases. In monitoring treatment responses, PIIINP and CA-125 were identical in 17 patients (57%), both being good predictors of the clinical behavior of the disease in 16 cases and poor predictors in one case. In 13 patients (43%) they were complementary to each other. In three cases PIIINP alone and in one case CA-125 alone were clinically useful prognosis indicators. During the period of complete clinical response to cytotoxic chemotherapy of 16 patients, the CA-125 concentrations decreased to normal before the clinical disappearance of the tumor in eight cases. PIIINP did so in only two cases, thus correlating more precisely with the presence of malignancy. In second-look laparotomies, PIIINP concentrations correlated with the presence of occult cancer better than those of CA-125. In predicting recurrent malignancy in patients with transient complete response, PIIINP and CA-125 were clinically equal. According to the present data, PIIINP concentrations often give information not obtainable by CA-125, thus being useful in monitoring the clinical behavior of ovarian cancer. PMID- 2924329 TI - Augmentation of host antitumor immunity by low doses of cyclophosphamide and mafosfamide in two animal tumor models. AB - By cloning in vitro we have obtained two sublines of the L5222 rat leukemia, one with high (L5222-S) and the other with low (L5222-R) in vivo sensitivities to non toxic doses of mafosfamide, a stabilized derivative of 4-hydroxy cyclophosphamide. This sensitivity in vivo was not related to the cytotoxic activity of the drug in vitro. Treatment of rats bearing the L5222-S and of mice transplanted with the MOPC-315 plasmocytoma with low doses of mafosfamide or cyclophosphamide resulted in a high percentage of surviving animals, which were resistant to a subsequent tumor challenge. Viable leukemic cells were needed to establish antitumor immunity, since it was not possible to induce resistance by injection of mitomycin-C-treated, non-viable L5222 cells. The adoptive transfer of spleen cells from animals immune against the L5222-S and the MOPC-315 resulted in resistance of the syngeneic recipients against a rechallenge with tumor cells, provided that the animals were treated with an immunosuppressive dose (100 mg/kg) of cyclophosphamide prior to the spleen cell implantation. In nude mice treatment of the L5222 with low doses of mafosfamide also resulted in surviving animals, however resistance to a second tumor challenge occurred only sporadically. The data presented confirm that therapy with cyclophosphamide or mafosfamide enhances host antitumor immunity but, contrary to previous reports, it could be demonstrated that successful tumor rejection was independent of T cells. PMID- 2924330 TI - Binding parameters of monoclonal antibodies reacting with ovarian carcinoma ascites cells. AB - Binding parameters were determined for four mouse monoclonal antibodies reacting with three antigens on the surface of fresh human ovarian carcinoma ascites cells, under nearly physiological conditions. The object of these experiments was to aid in the selection of the optimal monoclonal antibodies for intraperitoneal immunotherapy. The number of antigenic sites per cell, the effective equilibrium association constant (affinity) and the half-life for dissociation were: for Ab MH99, 1.2 x 10(6) sites/cell, (1.9-4.1) x 10(8) M-1, and 4 h; for Ab MX35, (3.2 4.1) x 10(5) sites/cell, (3.4-4.8) x 10(8) M-1, and greater than 10 h; and for Ab MW207, 1.3 x 10(5) sites/cell, (3.6-4.1) x 10(9) M-1, and 3.1 h, respectively. One of the antigens, MH99, is recognized by five different monoclonal antibodies, and competitive inhibition experiments demonstrated that two distinct determinants are present; this antigen is also recognized by the previously described Ab 17-1A. These binding data will aid the rational design of immunotherapy strategies. PMID- 2924331 TI - Obtaining an NIH grant: basic building blocks. AB - The purpose of this paper was to explain the NIH research grant process and highlight competencies for attracting research funding. This information should help readers obtain financial support for important cardiovascular research, especially in the prevention area. PMID- 2924332 TI - Central projections of the pineal complex in the silver lamprey Ichthyomyzon unicuspis. AB - The central projections of the pineal complex of the silver lamprey Ichthyomyzon unicuspis were studied by injection of horseradish peroxidase. The pineal tract courses caudally along the left side of the habenular commissure, and a few fibers penetrate the brain through the caudalmost portion of this commissure. Most of the fibers, however, continue caudally and enter the brain through the posterior commissure. The pineal tract projects bilaterally to the subcommissural organ, the superficial and periventricular pretectum, the posterior tubercular nucleus, the dorsal and ventral thalamus, the dorsal hypothalamus, the optic tectum, the torus semicircularis, the midbrain tegmentum, and the oculomotor nucleus. A few fibers decussate in the tubercular commissure, but the course of these decusate fibers could not be followed owing to the bilateral nature of the projections. No retrogradely labeled cells were found in the brain. With the exception of the projections to the optic tectum and torus semicircularis, the pineal projections in the silver lamprey are similar to those reported in other anamniote vertebrates. PMID- 2924333 TI - Cytochemical localization of type-A and -B monoamine oxidase in the rat pineal gland. AB - In the mammalian pineal gland, serotonin (5-HT) is located both in the pinealocytes and in the noradrenergic nerve terminals. Pineal 5-HT can be metabolized by three different routes, one of these being its deamination, catalyzed by monoamine oxidase (MAO). MAO is known to exist as two isozymes, MAO A and MAO-B. Using two different cytochemical methods at the ultrastructural level, we have localized the presence of MAO in the pineal gland of the rat. The use of selective inhibitors of A-type (clorgyline) and B-type (deprenyl) has shown that MAO-A is localized in the noradrenergic nerve terminals, while pinealocytes contain MAO-B. Taking into account that 5-HT is only deaminated by MAO-A, the specific association of each MAO isozyme with a defined cell type implicates that two cellular compartments are needed in the pineal gland for the biosynthesis of 5-methoxytryptophol and 5-methoxyindole acetic acid, while for the synthesis of melatonin and 5-methoxytryptamine just one cellular compartment, the pinealocyte, is appropriate. PMID- 2924334 TI - Immunohistochemical localization of vasoactive intestinal peptide (VIP) in the circumventricular organs of the rat. AB - The indirect peroxidase-antiperoxidase immunohistochemical technique was used to investigate the possible presence of vasoactive intestinal peptide (VIP) in the circumventricular organs of the rat. Considerable numbers of VIP-immunoreactive fibers were seen in the pineal gland. A moderate amount of VIP-immunoreactive fibers was present in the median eminence, the posterior lobe of the pituitary and the area postrema, but only few fibers were found in the organum vasculosum laminae terminalis. No immunoreactivity was observed in the subfornical organ or the subcommissural organ. The circumventricular organs investigated were completely free of VIP-immunoreactive perikarya. In the circumventricular organs, VIP-immunoreactive fibers were visible between the parenchymal cells and in the perivascular spaces. The presence of coarse VIP-immunoreactive terminals in apposition to the portal vessels in the external layer of the median eminence indicates that VIP may be secreted directly into the pituitary portal circulation, thus influencing the anterior pituitary cells. The presence of large VIP-immunoreactive boutons in the posterior lobe of the pituitary suggests a secretion of VIP directly into the systemic circulation. In the pineal gland, a dense innervation by VIP-immunoreactive fibers was found in the peripheral superficial part of organ, with fibers penetrating into its central portion where they mainly terminate near in vicinity of the capillaries. In the area postrema, VIP-immunoreactive material was mainly found at the ventral border of the organ. In addition to the secretion of VIP into the bloodstream via the circumventricular organs, this study provides evidence that VIP exerts specific influence on the cellular elements of these organs. PMID- 2924335 TI - Immunohistochemical localization of microtubule-associated proteins in the nervous system of the small intestine of guinea pig. AB - Layers containing Auerbach's and Meissner's plexuses were dissected from the small intestine of guinea pig and immunostained with affinity-purified antibodies against brain-specific microtubule-associated proteins (MAPs): MAP1, MAP2 and tau and a MAP with a molecular weight of 190,000 dalton purified from bovine adrenal cortex (190-kDa MAP). MAP1 antibody stained the network of nerve fibers and the cell bodies of enteric neurons in both Auerbach's and Meissner's plexuses. Staining with anti-tau antibody gave the same results. Antibody against MAP2 stained neuronal cell bodies and short thin processes extending from them. Interganglionic strands composed mainly of long processes were unstained. Anti 190-kDa MAP antibody stained both the neuronal cell bodies and bundles of nerve fibers. However, the staining was less intense than that with anti-MAP1 and tau antibodies. Differentiation in the structure of the cytoskeleton probably exists in the neuronal processes of the enteric neurons as is shown in the dendrites and axons in some neurons of the central nervous system. Thus, enteric neurons possess axon-like processes containing MAP1, tau and probably lower amounts of 190-kDa MAP. Cell bodies and dendrite-like structures of these neurons contain MAP2 in addition to MAP1, tau and 190-kDa MAP. PMID- 2924336 TI - Twenty-four-hour changes in pinealocytes, capillary endothelial cells and pericapillary and intercellular spaces in the pineal gland of the mouse. Semiquantitative electron-microscopic observations. AB - Semiquantitative electron-microscopic observations on the pineal gland of dd-mice were carried out to determine whether 24-h rhythms exist in pinealocytes, pericapillary and intercellular spaces and capillary endothelial cells. Nuclear and cytoplasmic areas of pinealocytes and the area of condensed chromatin in pinealocytes showed inversely related circadian rhythms; the former two increased, whereas the latter decreased, during the light period. The extent of pericapillary and wide intercellular spaces exhibited 24-h changes, with an increase and decrease occurring during the light period and the dark period, respectively. The cross-sectional area of endothelial cells decreased and the number of fenestrae increased during the light period; this was reversed during the dark period. The results suggest that the increase in the nuclear and cytoplasmic areas of pinealocytes, the area of pericapillary and wide intercellular spaces and the number of fenestrae, and the decrease in the area of condensed chromatin and endothelial cells during the light period may be related to an increase in synthetic activity of pinealocytes in the mouse. PMID- 2924337 TI - Three-dimensional observation of the fibroblast-like cells associated with the rat myenteric plexus, with special reference to the interstitial cells of Cajal. AB - An extensive cellular network becomes visible over the myenteric plexus of the rat after removal of the overlying tissues under the scanning electron microscope. The cells are mainly stellate and have many slender processes via which they interconnect. They form a three-dimensional network and are closely associated with the ganglia and nerve bundles, and also extend over the smooth muscle cells. They are considered to correspond to the interstitial cells of Cajal because of their peculiar arrangement and their topography. Transmission electron-microscopic evidence demonstrates that the majority of those cells have features of fibroblasts. Gap junctions and intermediate junctions are observed between these fibroblast-like cells, and also between them and smooth muscle cells. Examination of serial thin sections reveals that single fibroblast-like interstitial cells connect to both circular and longitudinal muscle cells via gap junctions. It is suggested that the network of interstitial cells conducts electrical signals. PMID- 2924338 TI - Androgenic control of antagglutinin secretion in the boar epididymal epithelium. An immunocytochemical study. AB - Antagglutinin, a specific protein synthesized by the boar epididymis, was secreted by the principal cells of the initial segment, the caput and the corpus, but was not detectable in the caudal cells. Castration completely abolished the synthesis and secretion of antagglutinin in all epididymal cells. Androgen replacement suggests that the epithelial cells from different segments have differential regulatory mechanisms. The proximal zone appeared refractory to exogenous testosterone; the median zone was a typical androgen-dependent region; and the caudal cells, where an unusual secretion of antagglutinin was detected, revealed still a different reaction pattern. It is postulated that these latter cells depend not solely on androgen but also or exclusively on other factors. Our results, which demonstrate a primary role of the Golgi complex in the secretory process in the epididymal cells, also suggest that the apical smooth endoplasmic reticulum may be implicated in the intracellular transport of glycoproteins to the cell surface. PMID- 2924339 TI - A comparison of muscle precursor replication in crush-injured skeletal muscle of Swiss and BALBc mice. AB - Muscle precursor replication in Swiss mice, in which muscle regeneration is exceptionally vigorous, was compared with previous data for regeneration in BALBc mice. The tibialis anterior muscles of 23 male and 15 female inbred Swiss SJL/J mice were crush injured, and tritiated thymidine injected into mice at various times after injury to label replicating muscle precursors. Lesion samples were taken 10 days after injury, processed for autoradiography, and grain counts of myotube nuclei analysed. Muscle regeneration was more vigorous in male compared with female Swiss mice, and in both was strikingly greater than that in BALBc mice in which there was extensive fibrous connective tissue throughout the lesions. Autoradiographic analysis showed that muscle precursor replication started at 24 hours in Swiss mice, 6 hours earlier than the onset at 30 hours in BALBc mice. Muscle precursor replication appeared to be more active 96 hours after injury in female Swiss compared with male BALBc and male Swiss mice respectively, although numbers of precursor cells replicating at other times were similar. It is not known whether the slight difference in onset of muscle precursor replication can alone account for the more complete muscle regeneration seen in Swiss mice. Similar studies were carried out in 11 male and 10 female F1 hybrid (SJL/J x BALBc) mice. Analysis of labelled myotube nuclei showed that muscle precursors did not synthesise DNA prior to 30 hours after injury, and regeneration resembled that of the parental BALBc strain. PMID- 2924340 TI - Immunocytochemical and ultrastructural studies on allografts of the pituitary neurointermediate lobe in the third cerebral ventricle of the rat. AB - Neurointermediate lobes from adult or 10-day-old rats were implanted by a stereotaxic procedure into the third ventricle of adult male rats, in an area close to the paraventricular nucleus. They were examined, using immunocytochemical and ultrastructural techniques, at times ranging from 1 week to 8 months. All grafts were recovered in a healthy condition although some rejection of the tissue was detected at the 1- and 2-week stages. In the neural lobe, clusters of pituicytes were scattered among the loose network of capillaries, most of which had a fenestrated endothelium. The intermediate lobe remained organized in compact avascular lobules. Axons similar to those projecting into the neurointermediate lobe in situ, but also axons of other types (e.g., somatostatinergic, enkephalinergic) penetrated the grafts. Synapses with melanotrophic cells in the intermediate lobe and neurohaemal contacts in the neural lobe were frequent from 2 1/2 months after transplantation. Immunocytochemical and ultrastructural characteristics indicated intense secretory stimulation of the melanotrophic cells in the early stages. All cells enclosed in a same glandular lobule reacted in a similar manner. In later stages, when re-innervation occurred, the cells recovered their initial characteristics. The overall effect of the re-innervation of the intermediate lobe grafted in this location is inhibitory, as in the lobe in situ. PMID- 2924341 TI - The effect of bromocriptine on the intermediate lobe of the rat pituitary: an electron-microscopic, morphometric study. AB - The morphological effect of chronic synthetic and secretory inhibition of the intermediate lobe of the rat pituitary induced by bromocriptine treatment was studied using morphometric techniques in combination with electron microscopy. On the basis of granule diameters, a heterogeneous cell population was shown in the normal intermediate lobe. Bromocriptine treatment did not induce any change in the volume fraction, number or location of electron-dense secretory granules. Instead, there was a shift toward a more homogeneous cell population containing smaller granules, the mean granule volume being reduced by approximately 30%. The volume fraction of electron-lucent granules or vacuoles was markedly reduced, indicating a functional significance of these organelles. The volume of the Golgi apparatus was not significantly altered, but the number of condensing granules within the Golgi area was reduced. The volume of the intermediate lobe was decreased, apparently due to a decrease in the mean cell volume. PMID- 2924342 TI - Early sexual differentiation of diencephalic dopaminergic neurons of the rat in vitro. AB - Development of dopaminergic neurons was investigated in dissociated cell cultures raised from the diencephalon of male and female rat fetuses from days 14 and 17 of gestation. Striking differences in morphology and function of male and female dopaminergic neurons were observed. Outgrowth of tyrosine hydroxylase immunoreactive processes initially proceeded at a faster rate in female than in male cultures. Morphological differences disappeared in cultures of gestational day 17. Irrespective of the age of the cultures and of the length of cultivation, the uptake capacity for (3H)dopamine per immunoreactive neuron was twice as high in female than in male cultures. Treatment of the cultures with sex steroids did not influence morphology, numbers or transmitter uptake of tyrosine hydroxylase immunoreactive neurons. The results suggest that diencephalic dopaminergic systems exhibit a sexual dimorphism that develops unexpectedly early in ontogeny and is independent of the action of gonadal hormones. PMID- 2924343 TI - Immunohistochemical localization of glutamate decarboxylase in the rat oviduct and ovary: further evidence for non-neural GABA systems. AB - The distribution of L-glutamate decarboxylase (GAD), a major biosynthetic enzyme for gamma-aminobutyric acid (GABA), was examined in the oviduct and ovary of the rat by means of an immunohistochemical technique. The polyclonal antiserum raised against brain GAD showed specific immunoreaction in some non-neuronal elements of the sex organs. In the oviduct, the inner layer of the mucosa was predominantly labelled. The selective distribution of GAD immunoreactivity in epithelial cells of the oviduct is consistent with former findings for GABA-like immunoreactivity in the same organ, indicating that the GAD-catalyzed reaction may be a major biosynthetic pathway for GABA even in these cells. In the ovary, vacuole-like formations within the follicular fluid and oocytes showed intense, specific staining. The occurrence of GAD immunoreactivity inside developing ovarian follicles including the oocyte may suggest a role for GABA related to follicular development and certain functions concerning the ovum. PMID- 2924344 TI - The roles of haemocytes during degeneration and regeneration of crayfish muscle fibres. AB - Crayfish haemolymph contains three types of haemocytes with cytoplasmic granules: coagulocytes, granulocytes and amoebocytes. Muscle degeneration was induced by either a gross mechanical injury or a mild puncture injury of m. extensor carpopoditi. Granulocytes and amoebocytes were involved in the phagocytosis of disintegrating muscle fibres. Within three weeks after the gross injury the first myotubes were found. The formation of regenerated fibres started before the degenerating material was removed completely. Mild injury resulted in the formation of contraction clots, localized at the ends of a fibre and connected to a persistent external lamina in the form of an empty sheath. The external lamina sheaths were invaded by amoebocytes. They arranged themselves into a superficial layer similar to an epithelium, formed gap junctions and zonulae adherentes, and showed an increase in the number of cytoplasmic microtubules. These transformed haemocytes retained their ability to engulf material of the disintegrating fibre. In about three weeks the number of microtubules in the transformed haemocytes decreased, and newly formed contractile filaments appeared. Satellite cells are present along the normal crayfish muscle fibres. Following their activation in degenerated material, they might conceivably induce the transformation of haemocytes into myogenic cells. PMID- 2924345 TI - Somatomedin C in the pancreas of young and adult, normal and obese, hyperinsulinemic mice. AB - Immunocytochemical, immunochemical and RNA-hybridization techniques were used to map the distribution of somatomedin C (Sm-C; insulin-like growth factor I; IGF-I) in the pancreas of young and adult lean and obese mice. The D cells in the islets of Langerhans showed intense cytoplasmic Sm-C immunoreactivity, extending into their processes. Only slight Sm-C immunoreactivity was seen in A and B cells, apparently confined to the plasma membranes. In the exocrine pancreas scattered duct cells were immunopositive. Starvation increased, while feeding decreased the Sm-C immunoreactivity in B cells. RNA-hybridization analyses revealed that roughly the same number of Sm-C mRNA molecules, as calculated per DNA amount in the pancreas, could be demonstrated in young and adult, lean and obese mice. Radioimmunoassay (RIA) determinations of total Sm-C showed that there were about equal concentrations in the pancreas of lean and obese mice. There were marked differences between the liver and the pancreas, in that the RIA Sm-C values for the former were twice those in the latter while, in contrast, the corresponding values for the Sm-C mRNA, i.e. the agent determining the synthesis of Sm-C, were about 100 times higher in the liver as compared to that in the pancreas. We interpret our results as follows: The D cells in the islets form and secrete Sm-C in both young and adult, lean and obese mice, while A and B cells bind, but do not necessarily synthesize this peptide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2924346 TI - Cooperation, not compulsion, in distribution of research materials. PMID- 2924347 TI - Mutually exclusive splicing of alpha-tropomyosin exons enforced by an unusual lariat branch point location: implications for constitutive splicing. AB - Alternative splicing of alpha-tropomyosin pre-mRNA involves mutually exclusive utilization of exons 2 and 3, exon 3 being preferentially selected in most cells. This mutually exclusive behavior is enforced by absolute incompatibility between the adjacent splice sites of the two exons, due to close proximity of the exon 3 branch point to exon 2. The branch point, with an associated polypyrimidine tract, is in an unusual location, 177 nt upstream of the acceptor, only 42 nt from the exon 2 splice donor site. Splicing of exon 2 to 3 is consequently blocked prior to formation of an active spliceosome complex. This block to splicing can be relieved by insertion of spacer elements that increase the donor site-branch point separation to 51-59 nt. The unconventional relative location of the constitutive cis splicing elements therefore provides a simple mechanistic basis for strict mutually exclusive splicing. These results not only demonstrate that the branch point is not specified by proximity to the splice acceptor site, but rather suggest that it is the acceptor site which is specified relative to the branch point. PMID- 2924348 TI - Measles virus editing provides an additional cysteine-rich protein. AB - The measles virus (MV) phosphoprotein (P) gene encodes two known proteins, P (Mr approximately 70,000), involved in viral transcription, and, in a different reading frame, C (Mr approximately 20,000). By a combination of cDNA cloning, cDNA and RNA sequencing, and in vitro translation, we demonstrate here that the MV P gene also expresses a third product (Mr approximately 46,000) containing the amino-terminal region of P but a different, cysteine-rich carboxy-terminal motif. This third protein is translated from mRNAs in which one G residue has been inserted after three genomically encoded Gs, a modification found in about 50% of the P mRNAs. A smaller fraction of transcripts contain several additional G residues. PMID- 2924349 TI - A novel pathway for glycan assembly: biosynthesis of the glycosyl phosphatidylinositol anchor of the trypanosome variant surface glycoprotein. AB - The trypanosome variant surface glycoprotein (VSG), like many other eukaryotic cell surface proteins, is anchored to the plasma membrane by a glycosyl phosphatidylinositol (GPI) moiety. This glycolipid is assembled first as a precursor (glycolipid A) that is then covalently attached to the newly synthesized polypeptide. We have developed a trypanosome cell-free system capable of performing all of the steps in the biosynthesis of the glycan portion of glycolipid A. Using [3H]sugar nucleotides as substrates, several biosynthetic intermediates have been identified. From structural analyses of these intermediates, we propose a pathway for GPI biosynthesis. Based on comparisons between the VSG GPI anchor and similar structures in other cells, we believe that this same pathway will apply to the GPI anchors, and the related insulin-mediator compound, of higher eukaryotes. PMID- 2924350 TI - In trypanosomes the homolog of the largest subunit of RNA polymerase II is encoded by two genes and has a highly unusual C-terminal domain structure. AB - We have isolated the genes encoding the largest subunit of all three classes of RNA polymerase from Trypanosoma brucei. While the pol II largest subunit is encoded by a single gene in all organisms examined to date, trypanosomes contain two copies of the gene. Both genes are expressed in the procyclic and bloodstream stages of the trypanosome life cycle. The two pol II genes differ from one another in their coding sequences by 21 silent substitutions and 4 amino acid substitutions. In the core part of the large subunit, the predicted polypeptides are similar to other eukaryotic RNA polymerases. Both trypanosome pol II polypeptides, like those of other eukaryotes, also have a unique C-terminal extension. However, this domain in the trypanosome polypeptides, unlike those of other eukaryotes, is not a tandemly repeated heptapeptide sequence. PMID- 2924352 TI - The state of plant biology: views from the other side of the fence. PMID- 2924351 TI - The Drosophila EGF receptor homolog (DER) gene is allelic to faint little ball, a locus essential for embryonic development. AB - Recessive lethal mutations in the genetic locus of the Drosophila EGF receptor homolog (DER) were isolated. Identification of mutations in the gene is based on assays of DER protein autophosphorylation activity. Most DER alleles show little or no in vivo autophosphorylation. The ability to monitor these activities in vivo and in vitro offers a preliminary insight into the functional defects in the different mutant proteins. The identification of the DER locus was also confirmed by partial rescue of the mutant phenotype with a DER P-element construct. Homozygous DER mutants display a complex embryonic phenotype. Most notably, the anterior structures deteriorate, ventral denticle bands are missing, the germ band does not retract, and the central nervous system shows a collapse of commissure and midline pattern. Mutations in DER were shown to be allelic to the previously described locus faint little ball. PMID- 2924353 TI - Ommatidia in the developing Drosophila eye require and can respond to sevenless for only a restricted period. AB - The sevenless gene encodes a putative cell surface receptor that is expressed in a highly specific and complex pattern in the developing Drosophila eye. We show here that this pattern is not required for the development of either the R7 cell or any other cell in the retina. By transiently expressing sevenless protein, we show that there is only a brief period during eye development when the sevenless protein is required for the formation of the R7 photoreceptor. Our results indicate that the specificity of the cell-cell signaling mediated by the sevenless protein is not achieved by regulating the distribution of the sevenless protein, but rather must reside in some combination of the temporal and spatial distributions of the sevenless ligand or other components of the sevenless signaling pathway. PMID- 2924354 TI - The beta-globin dominant control region activates homologous and heterologous promoters in a tissue-specific manner. AB - We have introduced a human beta-globin minilocus, containing the recently described dominant control region (DCR), the beta-globin or Thy-1 gene, and a thymidine kinase (tk)-neoR gene into erythroid and non-erythroid cells. Analysis of the transcription levels of the genes shows that the DCR directs high levels of human beta-globin, Thy-1 and tk-neo expression independent of integration sites in an erythroid-specific manner. The presence of the DNAasel hypersensitive sites at the 5' end of the locus is required for this effect on the homologous and heterologous gene. An analysis of the DCR chromatin in transfected mouse erythroleukemic cells suggests that the formation of the hypersensitive sites in this region precedes beta-globin gene expression. PMID- 2924355 TI - Measles in Canada. PMID- 2924356 TI - Measles--United States, 1987. PMID- 2924357 TI - Leptospirosis: a diagnosis to be kept in mind. PMID- 2924358 TI - Influenza activity in Canada. PMID- 2924359 TI - Communicable disease surveillance in Canada. Goals and case definitions. PMID- 2924360 TI - Internationally quarantinable diseases. PMID- 2924361 TI - Universal precautions. Report of a Consensus Committee Meeting. PMID- 2924362 TI - Universal prenatal screening for hepatitis B, Alberta, 1985-1988. AB - A cooperative effort to identify all newborn infants at risk of acquiring hepatitis B infection involving the Canadian Red Cross BTS, Health Units, hospitals, and private doctors has been in place in Alberta since 1985. Routine universal screening of all prenatal patients identifies just under 200 infected mothers per year and about 90% of their infants receive HBIG and HB vaccine in a timely manner and are protected against infection and becoming hepatitis B carriers. At least half of these infants would not be identified if a selective testing program was in place and the cost for this much less efficient policy would be at least 4 times higher. The cost per infant protected through the universal screening program is estimated to be less than $1275. Routine screening of prenatal patients for HBsAg in a public health-coordinated program is highly cost effective and efficient. It is recommended that all jurisdictions consider such a program as recommended by the ACIP unless the hepatitis B carrier state is known to be extremely rare. PMID- 2924363 TI - Multi-dose vials of xylocaine: does re-use predispose to HBV or HIV transmission? PMID- 2924364 TI - [Reconstruction and psychiatry]. AB - The programme of reconstruction which is under way and which is being implemented by our society makes us consider also controversial aspects which we observe in specialized disciplines of our health services. In psychiatry they have become more acute in the course of years due to the development of personal and tasks. The author draws attention to some problems in the theoretical sphere of the discipline and in ambulatory and institutional care. He deals with problems of training of personnel, consistent with the needs of society. PMID- 2924365 TI - [Initial experience with the Czech version of the Washington Psychosocial Seizure Inventory]. AB - The Czech version of the Washington psychosocial questionnaire for paroxysmal diseases (WPSI) was presented to 100 ambulatory patients selected at random at the Regional Clinic for Paroxysmal Diseases in Prague (55 men, 45 women). The results are compared with data in the literature on samples from other countries; the Czech sample has mostly median values. Comparison of the sub-groups of the Czech group revealed differences by sex (women had more problems in the scale of family background, men in the scale of vocational adjustment), by the duration of the disease (with a shorter duration of the disease greater financial difficulties were associated), and by the neurologist's evaluation of the development of the disease (on the whole patients with a favourable development of the disease had significantly more often a high score of the lie scale-40.5%). Those patients with a favourable development of the disease who had the score of the lie scale in the normal range had greater difficulties with interpersonal adaptation and adaptation at work than patients with an adverse development of the disease. PMID- 2924366 TI - [The role of the community physician in the care of persons with mental disorders]. AB - A report of the Chair of General Medicine of the Institute for Postgraduate Medical Training on the results of an investigation of the knowledge and abilities needed for the function of health community doctors and factory medical officers. The views of 187 psychiatrists and 231 leading health community doctors are compared. Suggestions are made for the solution of controversial problems as a basis for discussion. PMID- 2924367 TI - [The effect of the development of the group on the therapeutic effect]. AB - The authors compared the results of six-week treatment in a therapeutic community comprising 484 patients who had therapy in groups which were classified as "good" by their therapists, and 91 patients having therapy in groups, classified by the therapists as "poor". No significant difference was found in the two groups as regards mitigation of symptoms, insight, change of attitudes and behavior at the time of completion of treatment and after an interval of one year. Effective factors of group psychotherapy obviously are equally effective also in groups with which the therapists are not satisfied. PMID- 2924368 TI - [Invalidism due to mental disorders in the North Bohemia Region in 1986]. AB - The author gives an account of invalidity granted on account of mental diseases in the diseases in the North Bohemian region in 1986. From a total number of 235 invalidities on account of mental diseases according to the protocols of the assessment commissions of social security 215 were evaluated. This number is analyzed by diagnosed as listed in the international classification of diseases and causes of death, stating the mean age when invalidity was granted and also focused on the training of the patients, and finally according to relative values of invalidization in the districts of the North Bohemian region. Attention is drawn to the impact of mental diseases invalidity--more than half the invalidities are granted to persons under 40 years of age. These analyses serve district specialists for further evaluation of objective and subjective causes of invalidization. PMID- 2924369 TI - In vitro synergism of 4-hydroperoxycyclophosphamide and cisplatin: relevance for bone marrow purging. AB - Autologous bone marrow transplantation with 4-hydroperoxycyclophosphamide (4-HC) purged bone marrow gives long-term remission in almost half of relapsed acute nonlymphocytic leukemia and non-Hodgkin's lymphoma patients, but relapse of disease is the main cause of failure, suggesting ineffective purging in some cases. Cisplatin (CP) has activity against a variety of human tumors and is not commonly used for initial therapy of leukemia and lymphoma. Using established human leukemia cell lines, combinations of 4-HC and CP were investigated as a potential regimen for improving the ex vivo removal of leukemia cells from bone marrow. The cell lines (K-562 and Raji) were incubated for 1 (4-HC) or 4 h (CP), washed, and assayed for inhibition of colony formation in semisolid media. In both cell lines, CP (4h) was more potent than 4-HC (1 h). Combinations of the drugs in various molar ratios were studied after the cells were sequentially incubated with 4-HC and CP. The effects of the drugs were analyzed using the multiple drug-effect analysis of Chou and Talalay. Analysis of data on in vitro inhibition of colony formation suggested that all combinations studied were synergistic in both cell lines, with the greatest synergism being found in the Raji cell line. In addition, for K-562 cells we could detect at least a 4.6 log reduction in cloning with the CP:4-HC combination (1:10 molar ratio). We conclude that CP is a potential candidate in drug combinations for ex vivo bone marrow purging because of its high potency against human leukemia cell lines, its synergistic activity in combination with 4-HC, and its ability to reduce a high tumor burden when combined with 4-HC. PMID- 2924370 TI - In vivo activity on murine tumors of a novel antitumor compound, N-beta dimethylaminoethyl 9-carboxy-5-hydroxy-10-methoxybenzo[a]phenazine-6-carboxamide sodium salt (NC-190). AB - A novel antitumor compound, N-beta-dimethyl-aminoethyl 9-carboxy-5-hydroxy-10 methoxybenzo[a]-phenazine-6-carboxamide sodium salt (NC-190) was evaluated for its antitumor activity in experimental murine tumor systems. In the initial studies with P388 leukemia (i.p.-i.p.), NC-190 led to an increase of greater than 200% in life span (ILS), and 75% of the mice were alive on day 30, when the optimal dose (50 mg/kg, days 1-5) was given. Additionally, the compound had significant activities against i.p. inoculated mouse L1210 leukemia, B16 melanoma, M5076 reticulum cell sarcoma, sarcoma 180, mouse hepatoma MH134, and rat Yoshida sarcoma and Yoshida ascites hepatoma AH130. The optimal dose resulted in a greater than 280% ILS with a 30-day survival of 50% in mice with L1210 leukemia (100 mg/kg, days 1-5), a 156% ILS in mice with B16 melanoma (50 mg/kg, days 1-5), a 98% ILS with a 90-day survival of 25% in mice with M5076 reticulum cell sarcoma (25 mg/kg, days 1, 5, 9, and 13), a greater than 300% ILS with a 60 day survival of 50% in mice with sarcoma 180 (50 mg/kg, days 3-10), a 148% ILS with a 60-day survival of 25% in mice with MH134 (25 mg/kg, days 1-5), a 129% ILS with a 60-day survival of 12.5% in rats with Yoshida sarcoma (12.5 mg/kg, day 3 10), and a greater than 161% ILS with a 60-day survival of 50% in rats with AH130 (6.3 mg/kg, days 3-10). In the experiments with s.c. inoculated tumors, NC-190 not only inhibited tumor growth, but also increased the life span of mice with Lewis lung carcinoma or B16 melanoma. The 60-day survivors accounted for 60% and 30% in mice with Lewis lung carcinoma and B16 melanoma, respectively. The compound significantly inhibited the spontaneous lung metastasis of Lewis lung carcinoma by more than 90% when eight daily i.v. injections were given. NC-190 was active by the i.p., s.c., and i.v. routes. Five consecutive daily i.p. doses (days 1-5) were more effective than a single dose (day 1), two doses (days 1 and 5), or three doses (days 1, 5, and 9). NC-190 warrants further study as a potential antineoplastic agent against human neoplasms, as it has a broad spectrum of antitumor activity and inhibits metastasis. PMID- 2924371 TI - Comparative effectiveness of mitoxantrone and doxorubicin in overcoming experimentally induced drug resistance in murine and human tumour cell lines in vitro. AB - Using a range of cell lines of murine and human tumour origin in which relatively modest levels (2- to 17-fold) of drug resistance have been selected in vitro by exposure to a range of standard antitumour drugs, we compared the cytotoxic effects of doxorubicin (DOX) and mitoxantrone (MITO). In general, significantly lower concentrations of MITO than of DOX were required to achieve comparable cytotoxicity, confirming previously published data. MITO appears more generally effective against the murine L5178Y drug-resistant sublines than DOX, although there was no expression of collateral sensitivity to this newer agent. In the various human tumour lines there was a lack of cross-resistance to both DOX and MITO in two 5-fluorouracil (FU)-resistant lines and one of two cisplatin (CDDP) resistant cells, but cross-resistance was expressed in one subline resistant to vincristine (VCR) and two etoposide (VP-16)-resistant sublines. One murine and two human DOX-resistant sublines were effectively killed by MITO, whilst DOX proved effective against the human MITO-resistant subline. This apparent lack of cross-resistance between DOX and MITO in these resistant sublines expressing low levels of resistance in vitro therefore appears to contrast with previous reports involving highly multidrug-resistant DOX-selected sublines. However, since the latter lines generally exhibited profound cross-resistance to VCR and definite cross-resistance to VP-16, this may at least in part dictate their responses to MITO. Therefore, attempts to use experimentally derived drug-resistant sublines for preclinical drug screening should be approached with caution, since patterns of drug response appear to be influenced by the level of drug resistance expressed. The need remains to determine which type of model system provides the most relevant clinical information. PMID- 2924372 TI - Effect of homoharringtonine on the viability of murine leukemia P388 cells resistant to either adriamycin, vincristine, or 1-beta-D arabinofuranosylcytosine. AB - Cultured murine leukemia P388 cell populations were derived from P388 cells resistant to vincristine (P388/VCR), adriamycin (P388/ADR), and 1-beta-D arabinofuranosylcytosine (P388/ARA-C) that were developed in vivo and to the parental drug-sensitive cells (P388/O) that were passaged in vivo. The doubling times of the cultured cell populations (mean +/- SD) between cell densities of 5 x 10(4) and 1 x 10(6) cells/ml were 14.2 +/- 2 h (P388/O), 16.5 +/- 1.9 h (P388/VCR), 16.9 +/- 1.2 h (P388/ADR), and 15.0 +/- 1.4 h (P388/ARA-C). Exponentially proliferating cultured cell populations were exposed to selected homoharringtonine (HHT) concentrations for 24 h and the surviving cell fractions were determined by colony formation in semisolid medium. The results, based on differential sensitivity of the cell populations to HHT, indicated that cultured P388/VCR cells were cross-resistant to 0.018-1.8 micrograms/ml HHT, P388/ADR cells were cross-resistant to 0.058-1.8 micrograms/ml HHT, and P388/ARA-C cells were collaterally sensitive to 0.09-0.36 micrograms/ml HHT. The results with the cultured P388/VCR, P388/ADR, P388/ARA-C, and P388/O cell populations were confirmed in animal experiments. CD2F1 mice bearing intraperitoneal (i.p.) implants of 1 x 10(6) P388/VCR, P388/ADR, P388/ARA-C, or P388/O leukemia cells were given HHT i.p. qd on days 1-9 postimplantation. Optimal treatment (less than or equal to LD10) produced in vivo cell kills of 2 to 3 log10 units in P388/O and about 7 log10 units in P388/ARA-C, whereas P388/VCR and P388/ADR cells actually increased by 1-2 log10 units during treatment. The results of this study indicate that cross-resistance (P388/VCR and P388/ADR) or collateral sensitivity to HHT (P388/ARA-C) is a function of the cellular properties of the target tumor cell populations that is independent of host factors. PMID- 2924373 TI - Pharmacokinetics of methotrexate (MTX) and 7-hydroxymethotrexate (7-OH-MTX) in rats and evidence for the metabolism of MTX to 7-OH-MTX. AB - In pentobarbital anesthetized rats that received 4 mg/kg i.v. methotrexate (MTX) or 7-hydroxymethotrexate (7-OH-MTX), the pharmacokinetics of the two drugs were similar. Plasma concentrations of both drugs declined biexponentially, with terminal half-lives of 90.6 min for MTX and 97.2 min for 7-OH-MTX. The total clearance values were 9.2 and 9.6 ml x kg-1 x min-1, respectively. With MTX, 48.2% of the dose was excreted in the urine within 200 min and another 31.6% was recovered from the bile; 5.8% was metabolized to 7-OH-MTX and appeared in the bile. Plasma concentrations of the metabolite 7-OH-MTX after MTX administration were below the detection limit. Injected 7-OH-MTX was predominantly excreted into the bile (72.8% of the dose); only 11.2% could be recovered from the urine. Differences between the physicochemical properties of MTX and 7-OH-MTX or different affinities for active transport systems may account for the unequal importance of these two excretion pathways for the two compounds. PMID- 2924374 TI - Effect on liver tumor growth in rats of allopurinol and 5-fluorouracil in combination with hepatic artery ligation. AB - Rats with an experimental solitary liver tumor of a nitrosoguanidine-induced colonic adenocarcinoma were subjected to hepatic artery ligation (HAL) alone or in combination with 5-fluorouracil (5-FU) in three different doses, with or without the addition of allopurinol. The drugs were injected i.p. on 3 consecutive days before or after the HAL procedure. HAL alone significantly reduced the tumor growth compared with the control procedure (P less than 0.001). This observation was correlated with a significantly prolonged survival for the ligated animals (P less than 0.01). The administration of a low dose of 5-FU (15 mg/kg per day) in combination with allopurinol (100 mg/kg per day) enhanced tumor growth compared with that in animals treated with 5-FU only (P less than 0.01) or nontreated animals (P less than 0.05). A significant increase in survival was observed in animals given a high dose of 5-FU (60 mg/kg per day) after HAL compared with non-treated animals (P less than 0.001) as well as animals subjected to HAL alone (P less than 0.02). All animals receiving more than 15 mg/kg per day 5-FU before HAL succumbed within 10 days. The addition of allopurinol did not protect the animals against this mortality. These observations indicate that the effect of HAL followed by 5-FU is dose-dependent and that, at least in this treatment modality, allopurinol does not modulate the toxicity of 5-FU. PMID- 2924375 TI - Pharmacokinetics of tauromustine in cancer patients. Phase I studies. AB - The pharmacokinetic properties of tauromustine (TCNU) were studied in 31 cancer patients who participated in phase I trials. The patients received single oral doses of tauromustine in the range of 20-170 mg/m2. Plasma samples were taken over 24 h after administration and analysed for tauromustine by reversed-phase liquid chromatography. Parent TCNU could be demonstrated in the plasma of all patients. Its absorption was rapid (tmax = 38 +/- 22 min), the half-life was 57 +/- 22 min (mean +/- SD), and maximal concentration (Cmax) and AUC values were linearly related to the dose level. Thus, our study does not indicate dose dependent pharmacokinetics for the drug in the range of 20-170 mg/m2. Thrombocytopenia was the dose-limiting toxicity of TCNU; the reduction of platelet counts appeared to be linearly related to the log dose and Cmax and AUC values. TCNU appears to exhibit pharmacokinetic properties that are different from those of other nitrosoureas, which might be important for the clinical effect of the drug. PMID- 2924376 TI - A phase I clinical trial of recombinant human tumor necrosis factor given daily for five days. AB - A phase I trial of human recombinant tumor necrosis factor (rH-TNF) has been carried out in patients with advanced solid tumors. Sixty-six courses of the drug were given by 1 h IV infusion, daily for 5 days to 33 patients at doses of 5, 10, 20, 30, 45, 60, and 80 x 10(4) U/m2/day. All patients received isotonic saline (up to 21/day) and either indomethacin or ketoprofen. Acute toxicity resembled that seen with the phase I study of a single dose (5). Dose limiting toxicity was acute, rapidly reversible, hepatic dysfunction and hypotension. Hypertension during drug infusion and dyspnea were marked in some patients. There was one complete and one minor response, both in patients with renal cell carcinoma. The dose of 80 x 10(4) U/m2/day x 5 was poorly tolerated and the recommended starting dose for phase II studies is 60 x 10(4) U/m2/day x 5. Caution is recommended in treating patients with pre-existing hepatic function abnormalities, hypertension, hypotension or significant obstructive airway disease. PMID- 2924377 TI - Elevated plasma tamoxifen levels in a patient with liver obstruction. PMID- 2924378 TI - Studies on the pharmacokinetics of chlorambucil and prednimustine in patients using a new high-performance liquid chromatographic assay. AB - Following the oral administration of either chlorambucil/prednisolone or prednimustine to patients, the plasma levels of free chlorambucil and phenylacetic acid mustard, the beta-oxidation product of chlorambucil, were measured using a new high-performance liquid chromatographic (HPLC) assay. This assay permitted the simultaneous detection of the analyzed compounds with a lower limit of detection of 30 ng/ml. The pharmacokinetics of chlorambucil and phenylacetic acid mustard were found to be entirely different when prednimustine was administered as opposed to its components chlorambucil and prednisolone together. After the ingestion of the conjugate, the plasma concentration-time curves of chlorambucil and phenylacetic acid mustard showed a "delayed" pattern compared with those obtained after the administration of the components. The mean area under the concentration-time curves (AUCs) of prednimustine-derived chlorambucil and phenylacetic acid mustard were 25% and 40%, respectively, of the areas obtained after a stoichiometrically equivalent dose of chlorambucil. Free plasma prednimustine could not be detected at any time. This different pharmacokinetic behavior might offer an explanation for the superior therapeutic effects of prednimustine demonstrated by clinical studies. PMID- 2924379 TI - Preclinical pharmacology of the anthrapyrazole analog oxantrazole (NSC-349174, piroxantrone). AB - Oxantrazole (now designated as piroxantrone) is an anthrapyrazole analog under evaluation as a potentially useful anthracycline-like antitumor agent. In preparation for phase I clinical trials, we characterized certain aspects of oxantrazole preclinical pharmacology, including plasma stability, murine pharmacokinetics, in vitro/in vivo metabolism, and DNA damage following incubation with human tumor cells in culture. Oxantrazole was relatively unstable in fresh mouse and dog plasma and particularly unstable in fresh human plasma (t 1/2 less than 5 min at 37 degrees C). Its decomposition in plasma was prevented by the addition of ascorbic acid, suggesting oxidative degradation. Following rapid i.v. administration of oxantrazole to mice, plasma elimination was best described by a two-compartment open model with an elimination-phase half-life, total body clearance, and steady-state volume of distribution of 330 min, 458 ml/min per m2, and 87.9 l/m2, respectively. The c x t value calculated following i.v. administration of 90 mg/m2 oxantrazole to mice was 177 micrograms-min/ml. This value was subsequently used in a pharmacologically guided dose-escalation scheme for the oxantrazole phase I clinical trial. Oxantrazole was converted to a polar conjugate, presumably a beta-glucuronide, by rat but not mouse hepatic microsomal preparations and in vivo by the mouse. Oxantrazole introduced protein associated DNA strand breaks following incubation with a human rhabdomyosarcoma cell line. Repair of the damage was complete by 15 h. Clinical pharmacologic studies are currently under way in conjunction with the phase I clinical trial of oxantrazole. PMID- 2924380 TI - Tumor inhibition by titanocene complexes: influence on xenografted human adenocarcinomas of the gastrointestinal tract. AB - The present study deals with the influence of some bis(eta 5 cyclopentadienyl)titanium(IV) (titanocene) complexes, mainly represented by titanocene dichloride, on the development of several human gastrointestinal (GI) carcinomas (one stomach, seven colon, four sigmoid, and two rectal adenocarcinomas), all xenografted to athymic mice. In 10 of these 14 carcinomas, titanocene dichloride effected growth suppression of greater than 50% in comparison with control tumors. In the case of the stomach and two colon adenocarcinomas, absolute decreases in tumor volume occurred during and after the treatment period, resulting in growth delays of 6, 14, and 31 days, respectively. No sensitivity dependence was observed in the degree of tumor differentiation. The findings of the present study confirm the tumor-inhibiting activity of titanocene complexes against human GI adenocarcinomas. These results are noteworthy in view of previous clinical and experimental experience indicating that human adenocarcinomas of the stomach and colon are generally rather insensitive to common cytostatic agents. PMID- 2924381 TI - Pharmacokinetics of a new anticancer drug, navelbine, in patients. Comparative study of radioimmunologic and radioactive determination methods. AB - A study was designed to investigate the fate of navelbine (NVB) and its excretion routes in two cancer patients treated with tritiated NVB (30 mg/m2) by i.v. bolus injection. Plasma and red blood cell concentrations and urine and stool elimination were monitored over long periods of time. NVB plasma and urine concentrations were measured by both radioimmunoassay (RIA) and direct radioactive (RA) determination. Samples were also analyzed by high-performance liquid chromatography to evaluate the importance of NVB metabolism. Whereas the major excretion route for NVB was the stool (from 34% to 58.4% of the total dose given over 21 days), urinary excretion was low (about 21% within the same time period), corresponding mainly to that of unchanged drug. Thus, a good correlation was found between RIA and RA determinations in urine. In contrast, plasma area under the curve (AUC) values obtained after RA and RIA analysis differed markedly (AUC RIA/AUC RA = 0.23-0.31), demonstrating that a significant proportion of the plasma-circulating drug was biotransformed, mainly during the last elimination phase. This could have important pharmacological and toxicologic implications in clinical practice. PMID- 2924382 TI - Treatment of refractory and relapsed non-Hodgkin's lymphoma with ifosfamide, methotrexate and etoposide. AB - The combination of ifosfamide, etoposide and methotrexate was evaluated in 22 patients with non-Hodgkin's lymphoma (NHL) whose disease had relapsed or was resistant to first-line adriamycin-containing treatment. Only 4 of the 22 patients underwent remissions, 3 of which were complete and 1, partial. Two of the complete remissions occurred in patients with "high-grade" histology who received IMVP-16 after first-line treatment had induced only a partial remission. Bone marrow suppression was the limiting toxicity of this regime, which may be of value in the salvage therapy of selected patients with NHL. PMID- 2924383 TI - Phase I trial of a new nitrosourea, CGP 6809, given every 2 weeks. AB - A phase I study was carried out on a new water-soluble nitrosourea, 6-deoxy-3,5 di-O-methyl 6-(3 methyl-3-nitrosoureido)-alpha-D-glucofuranoside (EDMN, CGP 6809), given every 2 weeks. A total of 18 patients received doses of 1, 2, 3, and 3.75 g/m2 as a 2- to 5-h infusion. Toxicity principally involved nausea and vomiting, hepatotoxicity, and abdominal pain. There was no evidence of cumulative toxicity. The dose of 3.75 g/m2 was not exceeded because in a previous phase I study, 4.5 g/m2 every 6 weeks was not tolerated; the recommended dose for phase II studies is 3.75 g/m2 every 2 weeks. PMID- 2924384 TI - A large-scale cohort study on risk factors for primary liver cancer, with special reference to the role of cigarette smoking. AB - A large-scale cohort study in Japan (1966-1982) of life styles and primary liver cancer in men (123 out of 1,709,273 person-years) revealed a close association with cigarette smoking comparable to that for lung cancer, the relative risk (r.r.) for those smoking 1-29 and 30 or more cigarettes daily being 3.09 (1.78 5.35), 6.83 (3.56-13.10) for liver cancer, and 4.45 (3.77-5.25), 6.80 (5.51-8.41) for lung cancer, respectively. For liver cirrhosis, daily cigarette smoking was of less importance compared to daily alcohol drinking, r.r. = 1.17 (1.00-1.36) and 1.82 (1.63-2.04). However, for liver cancer, the risk from daily cigarette smoking was much higher than from daily alcohol drinking, r.r. = 3.14 (1.82-5.42) and 1.89 (1.40-2.55). The risk of liver cancer among the liver cirrhosis cases was therefore calculated as 2.67 (1.49-4.79) for daily cigarette smokers and 1.00 (0.72-1.38) for daily alcohol drinkers. These results must be of special importance in interpreting the reason for the increasing, unique mortality trend of liver cancer in men in recent years in Japan. PMID- 2924385 TI - Cooperative study on arterial regional chemotherapy for primary liver cancer in Hokkaido. AB - The Liver Study Group of Hokkaido analyzed a total of 57 patients with non resectable primary liver cancers, which were treated by intra-arterial adriamycin infusion chemotherapy combined with lipiodol and/or the Gelform embolization of the hepatic arteries. Of the ten patients considered clinical responders, three complete response patients and seven partial response cases were obtained. The overall response rate was 17.5%. The median survival period at each clinical stage was as follows: stage I: 13.0 months, stage II: 16.0 months, stage III: 11.5 months and stage IV: 4.7 months. The common side-effects of this treatment were nausea, vomiting and anorexia. Hematological toxicities were also found, but there was no patient who suffered from severe complications. PMID- 2924386 TI - Hepatic irradiation in primary and metastatic liver cancer. AB - Between December 1973 and September 1987, 21 patients with primary liver cancer and 41 patients with metastatic liver cancer were treated with external irradiation, intra-arterial infusion chemotherapy and/or transarterial embolization (TAE) at the National Medical Center Hospital, the National South Kyushu Central Hospital and the National Kure Hospital. Of the patients with primary liver cancer, 13 cases were treated with intra-arterial infusion chemotherapy (30-40 mg adriamycin or 10 mg mitomycin C) and hepatic irradiation. Eight cases were treated by TAE and hepatic irradiation. In the Child A group, the survival period of the chemotherapy + hepatic irradiation cases (mean: 608 days) was longer than that of the TAE + hepatic irradiation cases (mean: 216 days). The median survival period of all the cases was 7.0 months (mean: 10.9 months). For 16 of the 21 patients (who had absorbed over 40 Gy), the median survival period was 11.9 months (mean: 11.7 months). For 5 of the 21 patients (who had absorbed below 40 Gy), the median survival period was 4.3 months (mean: 7.9 months). Of the patients with metastatic liver cancer, the median survival period was 7.2 months (mean: 8.0 months). For 22 of the 41 patients (who had absorbed over 40 Gy), the median survival was 7.9 months (mean: 12.6 months). For 19 of the 41 patients (who had absorbed below 40 Gy), the median survival period was 1.7 months (mean: 2.6 months). The pretreatment serum GOT (glutamate oxaloacetate transaminase) levels and the pretreatment Karnofsky performance status index were the factors governing the prognosis of the cases with metastatic liver cancer, while toxicity was generally mild. PMID- 2924387 TI - Effect of caerulein on abdominal pain following transcatheter hepatic arterial embolization in malignant liver cancer patients. AB - The severity of pain occurring in the right hypochondrium after transcatheter hepatic arterial embolization carried out in the treatment of malignant hepatic tumors was compared between a caerulein-treated group and a non-caerulein-treated group. The caerulein-treated group and the non-treated group each comprised nine patients Gelfoam powder was used as an occlusive agent. Even though there were no statistically significant differences between the two groups, the caerulein treated group tended to demonstrate milder pain in the right hypochondricus, less incidence of tenderness and needed fewer administrations of analgesic than did the non-treated group. None of the three patients showing cystic artery contraction after the caerulein administration developed right hypochondricus pain or tenderness, or required the administration of analgesic. It was concluded that caerulein is useful in relieving right hypochondricus pain occurring after transcatheter hepatic arterial embolization. PMID- 2924388 TI - Liver resection using a water jet. AB - The water-jet method has been used during hepatic resection. The instrument cuts the hepatic tissue with the high pressure of the fine water flow, while the exposed elastic intrahepatic vessels are spared injury. A comparative study on the water-jet method with the previously employed conventional methods was undertaken. Hepatic resections were performed on 35 patients using the water-jet method. Cirrhosis of the liver was associated with 10 of the 24 patients with hepatocellular carcinoma. An ordinary saline solution was used as the jet, which was projected at a pressure of between 12 kg/cm2 and 20 kg/cm2 through a 0.15/mm diameter nozzle. A higher jet pressure was needed to cut the fibrotic hepatic parenchyma. In the case of normal liver, the intrahepatic vessels of more than 0.2 mm were well preserved. In most of the cases, the loss of blood when cutting the hepatic parenchyma can be easily reduced with a jet pressure of 15-16 kg/cm2, thus preserving the fine vessels more than 0.2 mm in diameter without injury. When the same pressure was applied in the cutting of a cirrhotic liver, it took much longer time compared to that of a non-cirrhotic normal liver parenchyma. The cut surface was smooth compared to that after using CUSA, although its disadvantages lie in the formation of air bubbles, which obscure the operative field. The controlled projection of a jet of water under optimal pressure may ensure a safe hepatic resection of both normal and cirrhotic livers. Furthermore, because of its uncomplicated form, a wide range of applications can be expected, while the lower cost will also expedite its large-scale use for economic reasons. PMID- 2924389 TI - The chemistry and biology of 7H-dibenzo[c,g]carbazole: synthesis and characterization of selected derivatives, metabolism in rat liver preparations and mutagenesis mediated by cultured rat hepatocytes. AB - Authentic stable standards of 7H-dibenzo[c,g]carbazole (DBC), a potent environmental carcinogen, were synthesized in order to study the compound's metabolism and mutagenesis in whole cell systems. Complete characterization of 2 OH-DBC, 3-OH-DBC, 4-OH-DBC, 13c-OH-DBC and N-methyl-DBC was accomplished by UV, IR, fluorescence and high resolution NMR spectra, and by high resolution mass spectrometric procedures. Metabolites of DBC were isolated and separated by HPLC from extracts of rat liver microsomal incubations and the medium of primary cultures of rat liver cells. Identification of metabolites was accomplished by comparisons between the authentic standards and isolated metabolites by UV and fluorescence spectroscopy, mass spectral analyses, and by co-chromatographic techniques. 2-OH-DBC and 3-OH-DBC were found in all rat liver preparations as well as three other unidentified phenols. 4-OH-DBC, 13c-OH-DBC or N-methyl-DBC were not isolated under any conditions. The rates of appearance of DBC metabolites in cultures of rat liver cells were compared to those for benzo[a]pyrene (BaP) at 10, 25, 50 and 100 microM substrate. At 25 microM substrate or greater, DBC metabolites appeared in the culture medium at significantly faster rates than those of BaP. At 100 microM substrate, DBC metabolites appeared at a rate approximately 4-times the rate observed for BaP. When the mutagenic potential of DBC was compared to that of BaP under identical conditions in a co-cultivation system of rat liver cells and an epithelial cell line, DBC was found to produce significantly higher rates of mutagenesis than BaP at concentrations of 0.4, 4.0 and 40.0 microM in the culture medium. The mutagenic potential of DBC was compared to that of several derivatives of the parent compound. 3-OH-DBC, 13c-OH-DBC and N-methyl-DBC were found to be mutagenic in the co-cultivation system at 40 microM, with mutation frequencies of 4.4 +/- 0.8, 8.0 +/- 3.1 and 12.9 +/- 5.4 mutants per 10(5) survivors, respectively. The parent compound induced 8.0 +/- 2.8 mutants per 10(5) survivors at the same concentration. 2-OH-DBC and 4-OH-DBC were not mutagenic under the same conditions. The studies have shown that metabolism of 7H-DBC leads predominantly to phenols in rat liver cells. The results of the mutagenesis experiments indicate that, of the derivatives studied, those associated by induction to the nitrogen are mutagenic. The latter studies suggest that the nitrogen is involved in the activation of the parent compound through inductive mechanisms. PMID- 2924390 TI - Effect of heterocyclic amines and beef extract on chromosome aberrations and sister chromatid exchanges in cultured human lymphocytes. AB - Two of the major bacterial mutagens formed in heated meat products, 2-amino-3 methylimidazo[4,5-f]quinoline and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline or the basic fraction of beef extract induced a low frequency of sister chromatid exchanges in human lymphocyte cultures in the presence of metabolic activation. Structural chromosome aberrations were not induced at comparable high concentrations in human lymphocytes with intact repair system, suggesting that repair or induction of point mutations are involved in the DNA-damaging effect of heterocyclic amines rather than structural chromosome aberrations. Accordingly it may be concluded that mammalian cells with both intact repair and enzyme systems are more relevant than bacterial systems for evaluating the carcinogenic potential of heterocyclic amines. PMID- 2924391 TI - The air pollutant 2-nitrofluorene as initiator and promoter in a liver model for chemical carcinogenesis. AB - 2-Nitrofluorene (NF), a model substance for nitrated polycyclic aromatic hydrocarbons, is present in exhaust from diesel- and petrol-driven vehicles, in exhaust from kerosene heaters, and in urban air and river sediments. Therefore the possible consequences of human exposure are important to elucidate. In the present study the initiating and promoting activity of NF was studied in a liver model for chemical carcinogenesis in the rat. Furthermore, the in vivo metabolism and formation of genotoxic metabolites of NF were investigated. NF was found to be a moderate initiator and a weak promoter when compared to diethylnitrosamine (DEN) and 2-acetylaminofluorene (AAF) respectively, both of which are potent carcinogens. Animals given NF excreted more urinary mutagenicity when compared to animals given AAF or DEN. PMID- 2924392 TI - Effect of dimethyl sulfoxide on the genotoxicity and metabolism of benzene in vivo. AB - The mechanism of the genotoxicity and metabolism of benzene (BZ) was investigated by using a free-radical scavenger, dimethyl sulfoxide (DMSO), to investigate the free radical mechanism in BZ metabolism. The presence of chromosomal breakage expressed as micronuclei (MN) in bone marrow polychromatic erythrocytes (PCE) and the presence of several BZ metabolites in the urine were monitored. Adult male ICR mice were exposed orally to DMSO after oral exposure to BZ (440 mg/kg b.w.). DMSO was administered either in different concentrations (1.25, 3.75 or 12.5% given at a volume of 0.01 ml/gm b.w.) or at different intervals after BZ exposure (1, 3 or 5 h). Each group consisted of five mice. It was found that the BZ induced MN frequency was reduced by DMSO from 48.8 +/- 5.6 (SEM) to 2.6 +/- 0.7 per 1000 PCE when DMSO (12.5%) was administered at 1 h after BZ exposure (P less than 0.01), to 3.4 +/- 0.8 at 3 h (P less than 0.01) and to 36.2 +/- 12.1 at 5 h (P less than 0.01). The reduction of the clastogenic effect of BZ by DMSO was also dependent upon the DMSO doses. The MN frequency was significantly reduced from 48.8 +/- 5.6 to 29.4 +/- 10.9 with 1.25% DMSO (P less than 0.01) to 20 +/- 7.6 with 3.75% (P less than 0.01) and to 2.6 +/- 0.7 with 12.5% DMSO (P less than 0.01). The presence of different metabolites of BZ such as hydroquinone, catechol, trans-trans muconic acid (MA, the oxidized form of trans-trans muconaldehyde, ttM), and total and conjugated phenol was evaluated in the urine of the exposed mice using HPLC. Among these metabolites, the quantity of MA was found to have the closest positive correlation with the MN frequency (P less than 0.007). Phenol but not the other monitored metabolites was also positively correlated with MN frequency (P less than 0.03). Thus, our data show that the formation of genotoxic metabolites from BZ probably involves hydroxyl radicals and ttM as well as phenol are likely to be responsible for the clastogenic effect of benzene in vivo. PMID- 2924393 TI - Modulation of dietary fat-promoted pancreatic carcinogenesis in rats and hamsters by chronic ethanol ingestion. AB - The effect of chronic ethanol ingestion on dietary fat-promoted pancreatic carcinogenesis was investigated in rats and hamsters. Rats were given a single i.p. injection of 30 mg azaserine per kg body wt at 19 days of age. Hamsters were injected s.c. with 20 mg N-nitrosobis(2-oxopropyl)amine (BOP) per kg body wt at 6 and 7 weeks of age. The animals were fed a semi-purified diet high in unsaturated fat (25% corn oil) either separately or in combination with ethanol. Ethanol was provided in drinking water at a concentration of 10% (w/v). A separate group maintained on a diet low in unsaturated fat (5% corn oil) was included as extra controls. The rats and hamsters were given their diets and received ethanol via their drinking water after treatment with carcinogen. Terminal autopsy of rats was 15 months after azaserine treatment and of hamsters 12 months after the last injection with BOP. Dietary fat was found to enhance pancreatic carcinogenesis in both rats and hamsters. In rats, ethanol slightly enhanced the multiplicity but not the incidence of malignant tumours, while in hamsters ethanol did not show any modulating effect on dietary fat-promoted carcinogenesis. It was concluded that dietary fat-promoted pancreatic carcinogenesis as observed in the animal models applied is not significantly modulated by chronic ethanol ingestion. PMID- 2924394 TI - Comparison of the in vitro metabolisms and mutagenicities of dibenzo[a,c]anthracene, dibenzo[a,h]anthracene and dibenzo[a,j]anthracene: influence of norharman. AB - The comparison of the behaviour of three dibenzoanthracene (DBA) isomers, dibenzo[a,c]anthracene (DB[a,c]A), dibenzo[a,h]anthracene (DB[a,h]A) and dibenzo[a,j]anthracene (DB[a,j]A), polycyclic aromatic hydrocarbons (PAHs), whose carcinogenicity varies from very potent to apparently inactive, has been carried out. Influence of norharman (NH; 9H-pyrido[3,4-b]indol) was investigated for mutagenicity (reversion of histidine prototrophy) on Salmonella typhimurium TA 100, using 3-methylcholanthrene (3-MC)-induced rat liver microsomes or S9 (post mitochondrial fractions). A correlation with its influence, on the in vitro metabolism of radiolabelled molecules by the same enzymatic systems, was carried out. NH enhances the mutagenicities of DB[a,c]A and DB[a,h]A which are very well known mutagenic and carcinogenic PAHs. Contrary to its two isomers, the mutagenic potency of DB[a,j]A, which is considered as a weak mutagen and not a carcinogen, is strongly inhibited by NH. The balance sheets of the in vitro metabolism by microsomal enzymes, where the conjugation is excluded, were reported with or without NH. In the presence of the latter, the amounts of remaining DBAs slightly decreased while the metabolites covalently bound to microsomal proteins strongly decreased and the amount of hydrophobic metabolites highly increased. At the same time, the HPLC elution profiles of the metabolism pathways of the three DBAs are found to be modified in a similar way by NH: some of the metabolites are highly enhanced, and for all three DBAs, a tetraol, not detectable in the absence of NH, emerges. The results are discussed with regard to possible effects of NH. PMID- 2924395 TI - The mouse-skin carcinogenicity of a mutagenic fraction from beech wood dusts. AB - A life-time mouse-skin carcinogenicity assay was conducted using female NMRI mice to evaluate the possible direct carcinogenic activity of a mutagenic fraction isolated from beech wood dusts. The samples of untreated beech wood dusts were extracted with methanol at pH3 and were purified from the inhibitory compounds toxic to bacteria, using silica-gel column chromatography. The fraction obtained after passing through the column was tested for mutagenicity in the Ames assay employing Salmonella typhimurium TA100 in the presence of Aroclor-treated rat liver-S9. Using acetone as the vehicle, this mutagenic fraction was tested for carcinogenicity on an area of 1-1.5 cm shaved skin of mice on the lower back. The mice were treated with half of each dose, twice a week, for only 3 months. The total doses applied per week were 2.5, 5, 7.5 or 10 g equivalent dust/mouse. No substance was used as promoter. No statistically significant difference was found when the life spans of treated and untreated animals were compared. The observed carcinogenic effect was based on tumours and lesions found only on the site of application of the test material. Of 210 mice (effective number, 129) serving as the negative controls, three developed skin lesions but no tumours. Of 280 treated animals (effective number, 188) 34 developed different types of tumours and 20 had a uniform type of precancerous skin lesion. Of 34 tumours observed 21 were originated from the skin, 12 from the mammary glands beneath the site of application, and one was a lymphoma. Comparing the negative controls with the treated animals, the overall carcinogenic effect observed was dose-dependent and statistically significant. Excluding the mammary tumours and a lymphoma found beneath the site of treatment, the overall induction of skin tumours was still significant. However, the dose-dependent increase in the number of skin tumours alone was not statistically significant. These results suggest that beech wood dust contains mutagenic and carcinogenic constituent(s). PMID- 2924396 TI - Relationship of oxidative damage to the hepatocarcinogenicity of the peroxisome proliferators di(2-ethylhexyl)phthalate and Wy-14,643. AB - Quantitative comparisons of the time course of biochemical and morphological changes induced by peroxisome proliferators resulting in low and high incidences of hepatic cancer have not been conducted previously under bioassay conditions. [4-Chloro-6-(2,3-xylidino)-2-pyrimidyl-thio]acetic acid (Wy-14,643) at 0.1% in the diet produced a much higher incidence of hepatic cancer in male rats than 1.2% di(2-ethylhexyl)phthalate (DEHP) in the diet. Both diets, however, caused similar degrees of peroxisome proliferation. To investigate this difference in carcinogenicity, H2O2-detoxification mechanisms and indices of oxidative damage were evaluated in male F-344 rats fed 1.2% DEHP or 0.1% Wy-14,643 for up to one year. DEHP or Wy-14,643 treatment increased hepatic catalase activity approximately 25% from 8 to 365 days. DEHP or Wy-14,643 treatment decreased hepatic glutathione peroxidase activity by 50% from 8 to 365 days. Glutathione concentrations were not affected by 151 days of DEHP or Wy-14,643 feeding. The similar effects of DEHP and Wy on H2O2 detoxification enzymes and glutathione concentrations suggests that these factors are not responsible for the widely different carcinogenicities of Wy-14,643 and DEHP. Hepatic vitamin E concentrations were 50% lower in rats receiving Wy-14,643 for 151 days as compared to rats fed DEHP or control diets. Lipofuscin, which was contained within lysosomes, was increased 3-fold after 39 days of DEHP and remained at this level up to 365 days of treatment. In comparison, lipofuscin was increased 4-fold after 18 days of Wy-14,643 and continued to accumulate in a linear manner reaching values 30-fold over controls after 365 days of treatment. DEHP treatment for 39-365 days increased the activities of the lysosomal enzymes alpha fucosidase, beta-galactosidase and N-acetylglucosaminidase 50-100%. The same enzyme activities were increased approximately 4-fold after 39-365 days of Wy 14,643. Lysosomal cathepsin B activity was unchanged by DEHP but doubled by 151 and 365 days of Wy-14,643. Acid phosphatase activity was unchanged by DEHP but increased by 50% after 151 and 365 days of Wy-14,643. In addition, conjugated dienes were increased (approximately 45%) only in rats receiving Wy-14,643 for 151 and 365 days. These data show for the first time that the magnitude and time course of lipofuscin deposition, induction of lysosomal enzymes and conjugated diene accumulation, is correlated closely with the degree of carcinogenicity. Wy 14,643-induced decreases in hepatic vitamin E concentrations could contribute to the observed accumulation of conjugated dienes at later time points.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2924397 TI - The conformations and electrostatic potential maps of phorbol esters, teleocidins and ingenols. AB - Phorbol esters and the structurally dissimilar teleocidins and ingenols bind to and activate protein kinase C (PKC) during the course of tumour promotion. These compounds are referred to as TPA-like tumour promoters (from 12-O-tetradencanoyl phorbol-13-acetate, the most active of the class) and are amongst the most potent tumour promoters known. Despite their structural dissimilarity, all three groups of molecules have been shown to bind to the diacylglycerol site of PKC with high affinity. It is thought that this binding to and consequent activation of PKC is the crucial step in tumour promotion by these compounds. The aim of this work was to provide a description of the binding site by comparing structural features (in particular the electrostatic potential) with the activity of numerous derivatives of the three classes. Initially the description was obtained by consideration of the phorbol derivatives, and then refined using the teleocidins and ingenols. The activity data were collected from a variety of sources and the structures calculated using the semi-empirical MNDO approximation embodied in the MOPAC program. Where possible, the crystal structure was obtained from the Cambridge Crystallographic Database, and used as a starting point for the calculation. In other cases, a preliminary calculation was carried out using the molecular mechanics program AMBER. Electrostatic potentials were calculated and displayed using an in-house program 3D2, while superpositions of molecules were carried out using CHEM-X. PMID- 2924398 TI - Evidence for two selenium-binding proteins distinct from glutathione peroxidase in mouse liver. AB - Labeling studies with 75selenium (75Se) have suggested the existence of selenium binding proteins in addition to glutathione peroxidase (GSH-Px) in rodent tissues. Three selenium-binding proteins of apparent mol. wt 56, 14 and 12K on SDS-PAGE were isolated from mouse liver using Sephadex G-150 and DEAE-Sephadex chromatography. The proteins were electroeluted from SDS-PAGE gels and injected into rabbits to elicit antibodies. Western immunoblot experiments indicated that the 56K protein was distinct from the 14 and 12K proteins. The latter two proteins appeared to be immunologically related, perhaps as differentially processed variants. The 56 and 14/12K proteins appeared to be distinct from GSH Px and the 57K plasma selenium-binding proteins. These results indicate that the mouse liver contains at least two selenium-binding proteins distinct from GSH-Px. The existence of the antibodies should permit experiments which help to examine the role of these proteins in the biological function of selenium in mammals. PMID- 2924399 TI - Urinary excretion of nitrate, nitrite and N-nitroso compounds in Schistosomiasis and bilharzia bladder cancer patients. AB - Saliva and 24-h urine samples were collected from male Schistosomiasis (bilharzia) patients with S. haematobium infection and possible concurrent S. mansoni infection without diagnosed bladder cancer (n = 27), bilharzia patients with diagnosed bladder cancer (n = 23) as well as a comparative control group (n = 27) of healthy Egyptian volunteers with no current bilharzia infection and/or bacterial urinary tract infections from the Nile Delta area of Egypt. Saliva samples were analysed for the presence of nitrate and nitrite; urine samples were analysed for the presence of nitrate, nitrite, volatile and non-volatile N nitroso compounds. Bilharzia patients prior to, and after, diagnosed bladder cancer regularly excreted free nitrite as well as volatile nitrosamines (N nitrosodimethylamine, N-nitrosodiethylamine, N-nitrosopiperidine and N nitrosopyrrolidine) in addition to which elevated concentrations of non-volatile N-nitrosamino acids (N-nitrosoproline, N-nitrososarcosine, N-nitrosothiazolidine 4-carboxylic acid and its 2-methyl derivative) were also present. Total urinary excretion of volatile N-nitroso compounds (0.32 +/- 0.64 micrograms/day; mean +/- SD) and non-volatile N-nitroso compounds (31.20 +/- 22.07 micrograms/day) was observed in the Egyptian control group. Significantly higher concentrations were found in bilharzia patients: 3.47 +/- 6.42 (P less than 0.05) and 62.91 +/- 21.96 (P less than 0.05); as well as in bilharzia patients with diagnosed bladder cancer: 1.71 +/- 1.96 (P less than 0.02) and 44.94 +/- 7.31 respectively. Free nitrite was found in the urine of two volunteers in the Egyptian control group (1.7 and 3.0 micrograms/day), urinary nitrite was significantly increased in bilharzia patients (5.18 +/- 9.11 micrograms/day, P less than 0.02) and in bladder cancer patients (1.75 +/- 2.81 micrograms/day, P less than 0.05). Nitrate concentrations were elevated from 139.3 +/- 82.2 in the control group to 143.6 +/ 136.3 and 175 +/- 190 in the bilharzia and bladder cancer groups respectively. These results indicate that significant in vivo formation of nitrite and volatile N-nitroso compounds occurs in the urinary bladder of bilharzia patients and this may be an oetiological factor in the induction of bilharzial bladder cancer associated with S. haematobium infection. PMID- 2924400 TI - S-adenosylmethionine, S-adenosylhomocysteine and DNA methylation levels in the liver of rats fed methapyrilene and analogs. AB - The antihistamine methapyrilene (hydrochloride) and four close structural analogs, methaphenilene, methafurylene, thenyldiamine and clorothen, were given to rats at a concentration of 0.1% in drinking water for 34 weeks. Only methapyrilene produced notable histopathological changes in the liver, bile duct hyperplasia and focal cellular change. Methapyrilene produced an early and persistent elevation in the ratio of S-adenosylmethionine to S adenosylhomocysteine, which was 2.8 times the control levels at 34 weeks; none of the other antihistamines produced so high a ratio or altered the ratio as early. Methapyrilene, but not the other antihistamines, produced a significant increase in the methylation of liver DNA at 20 and 34 weeks, as measured by the level of 5 methyldeoxycytidine. The increase in deoxycytosine methylation is so far the only detected effect of the carcinogen methapyrilene on DNA which is absent in rats treated with its non-carcinogenic analogs. PMID- 2924401 TI - In situ freezing of the urinary bladder: a trigger of rapid development of sodium o-phenylphenate-induced urinary bladder tumors in the rat. AB - The effect of in situ freezing of the urinary bladder on sodium o-phenylphenate (OPP-Na)-induced urinary bladder tumor development was investigated in male F344 rats. Freezing was performed at the start of the experiment by touching the serosal surface of the bladder with a frozen steel rod. As a result, three out of 27 rats (11%) developed bladder tumors within 78 weeks when 0.5% OPP-Na feeding was started 2 weeks after freezing and one out of 27 rats (4%) when the feeding was started 12 weeks after freezing. 0.5% OPP-Na alone did not induce any bladder lesions. In a second experiment, 19 out of 25 rats (76%) developed bladder tumors (carcinomas in 12 rats and papillomas in seven rats) when 2% OPP-Na was administered from 6 weeks after freezing, whereas only one rat (5%) demonstrated a bladder carcinoma in the group given 2% OPP-Na without prior freezing. In neither experiment were tumors induced by freezing alone. Enzyme histochemistry revealed no remarkable changes in enzyme activities of regenerative hyperplasia induced by freezing. The results indicate that in situ freezing of the urinary bladder acts as a trigger of rapid development of OPP-Na-induced rat urinary bladder tumors. PMID- 2924402 TI - Levels of mutagens in the urine of smokers of black and blond tobacco correlate with their risk of bladder cancer. AB - Levels of urinary mutagens, thioethers, N-nitrosamino acids, nitrate, nicotine, cotinine and creatinine were measured in 21 non-smokers, 26 smokers of blond tobacco, 9 smokers of black tobacco and 5 smokers of both types of tobacco, all eating a similar diet. Results were expressed either per 24 h urine or per mmol creatinine. The sum of urinary nicotine and cotinine levels (N + C) was used as a measure of exposure to the number of cigarettes smoked. Statistically significant positive dose-effect relationships were obtained between the urinary N + C levels and (i) the number of revertants (Salmonella typhimurium TA98, with a metabolic activation system); (ii) the concentration of thioethers; (iii) the levels of N nitrosoproline or the sum of all nitrosamino acids excreted and (iv) the amount of urinary nitrate. No such correlation was found between N + C levels and induction potency in the SOS chromotest. A linear dose-effect relationship between urinary mutagenicity (i.e. log revertants of S. typhimurium TA98) and N + C levels or number of cigarettes per day was established for smokers of blond tobacco. After adjustment for N + C levels, the urine of smokers of black tobacco contained twice as much mutagenic material as did the urine of blond tobacco smokers (P = 0.02). For other exposure markers, no statistically significant difference was found between the two types of smokers. Epidemiological studies have shown that the risk of urinary bladder cancer is 2.5 times higher in smokers of black tobacco than in blond tobacco. Therefore, our findings on urinary mutagenicity provide experimental evidence that the type of tobacco is the factor responsible for the observed difference in risk and that smoking of black as compared to blond tobacco results in a higher exposure of the urinary bladder to genotoxic hence potentially carcinogenic substances. PMID- 2924403 TI - Induction of tumors in the Zymbal gland, oral cavity, colon, skin and mammary gland of F344 rats by a mutagenic compound, 2-amino-3,4-dimethylimidazo[4,5 f]quinoline. AB - A mutagenic compound, 2-amino-3,4-dimethylimidazo[4,5-f]quinoline, which was first isolated from broiled sardines and was shown to be carcinogenic to mice, was also found to be carcinogenic to F344 rats. It induced tumors in various organs, such as the Zymbal gland, oral cavity, colon, skin and mammary gland of male and female rats when given at 0.03% in the diet. However, it was noteworthy that tumors were not observed in the liver. Most of the tumors in the Zymbal gland, oral cavity and skin were squamous cell carcinomas, and most of the mammary gland tumors were adenocarcinomas. The colon tumors were identified as adenomas or adenocarcinomas. In control rats no tumors developed in these organs during the 40-week experiment. PMID- 2924404 TI - Reduced accumulation of I-compounds in liver DNA of rats fed a choline-devoid diet. AB - Groups of rats were fed for 1, 4 or 7 months choline-devoid or choline supplemented diets, that provided approximately 50% of the methionine, and 0.15% or 150% of the choline requirements of young, growing rats. Liver DNA was isolated and analyzed by the nuclease P1-enhanced version of the 32P-postlabeling assay, which detects aromatic/hydrophobic DNA adducts and I-compounds (adduct like DNA modifications shown to accumulate in tissue of aging rats). DNA adducts and qualitative differences in the patterns of I-compounds were not observed in rats fed the two diets. However, in rats fed the choline-devoid diet there was a drastic reduction in the accumulation of I-compounds, compared with that in rats fed the control diet. These results extend previous evidence of a lack of relevant DNA adducts in the liver of rats fed the choline-devoid diet, and suggest the possibility of a role of I-compounds in the carcinogenicity of this diet. PMID- 2924405 TI - Phenobarbital promotion in diethylnitrosamine-initiated infant B6C3F1 mice: influence of gender. AB - Phenobarbital (PB) promotes hepatic tumorigenesis when chronically administered to male B6C3F1 mice after initiation with diethylnitrosamine (DENA) at 30 days of age. In contrast, when male B6C3F1 mice were initiated with DENA at 15 days of age, an inhibition of hepatic tumorigenesis occurred. The present study was undertaken to evaluate the influence of gender on the inhibiting ability of PB in the 15 day old DENA-initiated B6C3F1 mouse. Mice were injected with either DENA (5 micrograms/g) or saline at 15 days of age. At weaning mice were given either PB (500 p.p.m.) containing drinking water or deionized drinking water for 24 weeks. Male mice treated with DENA and PB demonstrated a significant decrease in the number of hepatocellular adenomas compared to males receiving DENA only. In contrast, females exposed to DENA and PB exhibited an enhancement of hepatic adenoma number compared to those receiving only DENA. In an additional experiment, individual preneoplastic foci from male and female B6C3F1 mice initiated with DENA at 15 days of age were examined for their responsiveness to the mitogenic stimuli of PB. Mice were exposed to either PB-containing or PB-free drinking water for 7 days. In non-PB treated males and females, preneoplastic hepatocytes demonstrated higher rates of DNA synthetic labelling compared to normal hepatocytes with no gender difference noted. Males exposed to PB exhibited increased levels of DNA synthesis in normal cells but not in preneoplastic foci. Females treated with PB, however, demonstrated significant increases in DNA synthesis in both preneoplastic and normal hepatocytes compared to non-PB treated females and PB-treated males. These findings suggest that in male mice initiated with DENA at 15 days of age, the preneoplastic foci are refractory to the proliferative effects of PB which may account for the observed inhibition of hepatic tumorigenesis by PB in this mouse strain. PMID- 2924406 TI - Inhibitory effect of magnesium hydroxide on methylazoxymethanol acetate-induced large bowel carcinogenesis in male F344 rats. AB - The effect of dietary magnesium hydroxide on colon carcinogenesis induced by methylazoxymethanol (MAM) acetate was examined in male F344 rats. MAM acetate was administered by i.p. injection to rats at 25 mg/kg body wt once per week for 3 weeks. Starting 2 weeks after the final MAM acetate exposure, the diet containing 500 or 1000 p.p.m. magnesium hydroxide was fed for 227 days. In the groups receiving magnesium hydroxide and MAM acetate, the incidence of colon neoplasms was decreased when compared with that in the group given MAM acetate alone. The inhibitory effect of dietary magnesium hydroxide on MAM acetate-induced colon carcinogenesis was greater at the lower dose than that at the higher dose of magnesium hydroxide in the diet. Neoplasms in other organs were rare and were not affected by the dietary magnesium hydroxide. PMID- 2924407 TI - In vitro polymerization of histones by carcinogenic nickel compounds. AB - This study was undertaken to explore whether nuclear chromatin constituents can participate in and/or be affected by redox reactions catalyzed by nickel, like those of nickel complexes with small peptides, e.g. tetraglycine (G4) and oxygen. Calf thymus DNA, nucleohistone (NH) or free histones were incubated at 37 degrees C, pH 7.6, for up to 96 h with nickel(II)acetate (NiAcet) or nickel subsulfide (Ni3S2) and/or G4. The effects on DNA and NH were studied by means of melting profiles. Free individual histones and histones extracted from NH prior to and after exposure to nickel compounds and/or G4 were examined by electrophoresis on polyacrylamide gels. Two-day exposure of DNA to NiAcet, G4, or NiAcet + G4 had no significant effect on its melting temperature. Incubation of NH with NiAcet, however, markedly increased its melting temperature by 2.2 +/- 0.3 degrees C after 24 h and 3.0 +/- 0.5 degrees C after 96 h (P less than 0.01 versus NH alone at either time). Incubation of NH with NiAcet + G4 also resulted in a significant rise of the melting temperature by 1.4 +/- 0.3 degrees C after 24 h (P less than 0.05) and 5.5 +/- 0.3 degrees C after 96 h (P less than 0.0001). G4 alone had no effect. Exposure of NH to NiAcet + G4, but not to the individual chemicals, slowly decreased solubility of the histone components in 0.2 M H2SO4. Only trace amounts of histones could be extracted from NH with acid after 72-h exposure to NiAcet + G4. Treatment of free histones with NiAcet, Ni3S2 and/or G4 resulted in a slow random polymerization of the proteins by NiAcet + G4, Ni3S2 + G4 and Ni3S2 alone, but not NiAcet or G4 alone. The action of Ni3S2 alone was slower than that of either nickel compound combined with G4. The present findings indicate that nickel carcinogens NiAcet and Ni3S2, in the presence of G4 or even alone (Ni3S2), are capable of causing protein-protein and perhaps also protein-DNA crosslinking. Reactions of this type may be involved in the mechanism(s) of nickel carcinogenesis. PMID- 2924408 TI - Inositol hexaphosphate inhibits large intestinal cancer in F344 rats 5 months after induction by azoxymethane. AB - A treatment regimen of 2% Na-InsP6 in drinking water was effective in significantly reducing large intestinal cancer in F344 rats even when the treatment was begun 5 months after carcinogenic induction with azoxymethane (AOM 8 mg/kg/wk X 6). Compared to untreated (AOM-only) rats, animals on InsP6 had 27% fewer tumors (P less than 0.02). The tumors were approximately two-thirds smaller in size (P less than 0.01) and percentage mitotic rate in the non-neoplastic epithelium was less than half (1.0 +/- 0.1, compared to 2.3 +/- 0.2 of AOM-only animals, significant at P less than 0.001). We postulate that InsP6 may exert its antineoplastic effect by way of regulating cellular proliferation even after effective carcinogenic stimuli and thus may be an important candidate for chemointervention. PMID- 2924409 TI - Sudden coronary death in the United States: 1980-1985. AB - To describe patterns of an indicator of sudden coronary death, data from the National Center for Health Statistics were examined for deaths occurring out of hospital and in the emergency room (OH/ER) from 1980 to 1985 in 40 states. In 1985, 56% of ischemic heart disease deaths occurred OH/ER among persons aged 35 74 years. The percentage occurring OH/ER declined with age, was higher in men than women, and higher in blacks than whites. At age 55-64, 61% of ischemic heart disease deaths in white and 66% in black men occurred OH/ER. Between 1980 and 1985, age-adjusted death rates in white men aged 35-74 years declined 19% for OH/ER and 18% for in-hospital ischemic heart disease deaths. The percentage of deaths in ER increased. The decline in deaths occurring OH/ER accounted for 61% of the total absolute decline in ischemic heart disease death rate in white men, 55% in white women, and about 70% in nonwhites. The decline in rates of death OH/ER should encourage further efforts at preventing coronary heart disease and improving emergency medical services. PMID- 2924410 TI - Effect of surgical reduction of left ventricular outflow obstruction on hemodynamics, coronary flow, and myocardial metabolism in hypertrophic cardiomyopathy. AB - To assess the impact of operative reduction of left ventricular outflow obstruction in hypertrophic cardiomyopathy, measurements of great cardiac vein flow, oxygen and lactate content, left ventricular pressures, and cardiac index were measured at rest and during pacing stress in 20 consecutive patients (13, myotomy-myectomy; six, mitral valve replacement; one, both myotomy-myectomy and mitral valve replacement) who underwent both preoperative and postoperative studies. All had angiographically normal epicardial coronary arteries. Operation resulted in reduction in outflow gradient (64 +/- 38 to 4 +/- 7 mm Hg, p less than 0.001) and in left ventricular systolic pressure (186 +/- 32 to 128 +/- 22 mm Hg, p less than 0.001) and was associated with reduction in great cardiac vein flow (101 +/- 26 to 78 +/- 16 ml/min, p less than 0.001) and oxygen consumption in the anterior left ventricle and septum (11.9 +/- 4.1 to 8.4 +/- 1.9 ml O2/min, p less than 0.001) in the basal state. During rapid atrial pacing, 13 of 20 patients experienced chest pain postoperatively, whereas all 20 developed chest pain during preoperative pacing, with an improvement in pacing anginal threshold (or heart rate 150 if no chest pain was experienced) of 16 +/- 18 beats/min (p less than 0.001). The peak great cardiac vein flow (161 +/- 41 to 131 +/- 45 ml/min, p less than 0.025) and myocardial oxygen consumption (19.4 +/- 6.1 to 14.3 +/- 5.5 ml O2/min, p less than 0.005) during pacing, which correlated directly with the severity of the basal left ventricular gradient (p = 0.011 and p = 0.002, respectively), were also reduced by surgery. Lactate metabolism during pacing changed from net production before surgery to net consumption after operation (-17 +/- 47.6 to 4.4 +/- 29.8 mumol/min, p less than 0.01), with six of 20 patients producing lactate after surgery compared with 13 of 20 before surgery (p = 0.06). The six patients with the highest peak great cardiac vein flow (greater than 175 ml/min) during preoperative pacing had greater symptom and metabolic benefit during pacing after surgery compared with the 14 patients with lower peak coronary flow. Postpacing left ventricular end-diastolic pressure (30 +/- 7 to 23 +/- 7 mm Hg, p less than 0.001) and pulmonary artery wedge pressure (24 +/- 6 to 20 +/- 5, p less than 0.001) were reduced after surgery.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2924411 TI - Epinephrine-induced reversal of verapamil's electrophysiologic and therapeutic effects in patients with paroxysmal supraventricular tachycardia. AB - The purpose of our study was to determine whether an infusion of epinephrine reverses the electrophysiologic effects of verapamil and whether reversal of verapamil's effects on the induction of paroxysmal supraventricular tachycardia (PSVT) by epinephrine during electropharmacologic testing is predictive of stress related recurrences of PSVT during long-term treatment with verapamil. The infusion rates of epinephrine used in this study were 25 and 50 ng/kg/min, which previously have been demonstrated to result in plasma epinephrine concentrations in the range that occurs during a variety of stresses in humans. The subjects of this study were 17 patients with recurrent PSVT who underwent an electrophysiologic study in the control state and after at least 2 days of treatment with 240-480 mg/day verapamil. After assessing the response to verapamil, epinephrine was infused and testing was repeated. Verapamil significantly slowed atrioventricular conduction and prolonged refractoriness in the atrium and atrioventricular node. The effects of the two infusion rates of epinephrine were generally similar in magnitude and, therefore, the results were pooled. Epinephrine partially or completely reversed all of verapamil's electrophysiologic effects. Verapamil suppressed the induction of sustained PSVT in 15 patients. Epinephrine facilitated the induction of PSVT in seven of these 15 patients. All 15 patients were treated on a long-term basis with verapamil. The eight patients in whom epinephrine did not facilitate the induction of PSVT had no recurrences of PSVT during 9-18 months of follow-up.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2924412 TI - Importance of collateral circulation for prevention of left ventricular aneurysm formation in acute myocardial infarction. AB - The effect of preexistent coronary collateral perfusion on the prevention of left ventricular aneurysm formation was examined in 47 patients undergoing an intracoronary thrombolysis within 6 hours after the onset of a first acute anterior myocardial infarction. Left ventricular aneurysm formation and wall motion were analyzed with cineventriculography. A left ventricular aneurysm was determined as well-defined demarcation of the infarcted segment from normally contracting myocardium. In 25 patients with successful thrombolysis (group A), a left ventricular aneurysm was observed in one patient (4%) during the chronic stage of infarction. In 10 patients who had a significant collateral circulation to the infarct-related coronary artery and unsuccessful reperfusion (group B), the left ventricular aneurysm was observed in only one patient (10%). In the remaining 12 patients with unsuccessful recanalization in the absence of a significant collateral perfusion (group C), there was a higher incidence (seven of 12, 58%) of left ventricular aneurysm formation than in groups A and B (p less than 0.05). In group A, both the global ejection fraction and regional wall motion in the infarct areas improved significantly (p less than 0.05) between the acute and chronic stages of infarction. By contrast, in groups B and C, these indexes on the ventricular function did not change significantly during the convalescent period. Thus, although the collateral perfusion existing at the onset of acute myocardial infarction may not improve ventricular function, it exerts a beneficial effect on the prevention of left ventricular aneurysm formation. PMID- 2924413 TI - Evidence for cholinergically mediated vasodilation at the beginning of isometric exercise in humans. AB - Vasodilation occurs in the nonexercising forearm at the beginning of isometric handgrip despite activation of sympathetic vasoconstrictor reflexes. The mechanism of this response remains unclear. In 33 normal humans, age 24 +/- 1 years (mean +/- SEM), we measured mean arterial pressure, heart rate, and forearm blood flow (plethysmography) in the nonexercising arm during sustained contralateral isometric handgrip at 30% maximal voluntary contraction. Sympathetic nerve activity to calf muscles (microneurography) was also measured in 15 subjects. Handgrip resulted in increases in arterial pressure from 86 +/- 2 to 97 +/- 3 mm Hg (p less than 0.05). Despite increases in nerve activity to calf muscles from 229 +/- 43 to 337 +/- 66 units (p less than 0.005), which would be expected to produce forearm vasoconstriction, forearm vascular resistance in the contralateral resting arm decreased from 20 +/- 3 to 18 +/- 2 units (p less than 0.05). To determine the mechanism of this vasodilatory influence, additional studies were performed with regional autonomic blockade with intra-arterial administration of atropine (0.8 mg, 10 subjects) or propranolol (2.0 mg, eight subjects) into the nonexercising forearm before contraction. Propranolol and vehicle had no effect on forearm vascular responses in the resting arm during SHG in the other arm. In contrast, atropine blocked the vasodilatory response in the resting arm during contraction (delta forearm vascular resistance during contraction, control = -2.1 +/- 0.6 units; postatropine = +0.2 +/- 0.9 units, p less than 0.05). Atropine did not attenuate the vasodilator response to isoproterenol or the vasoconstrictor response to norepinephrine. We conclude 1) a dissociation exists between sympathetic neural and forearm vascular responses to isometric exercise; 2) the vasodilatory response in the nonexercising forearm is not due to sympathetic withdrawal or beta 2-adrenergic-mediated vasodilation; and 3) this response is mediated primarily by cholinergic mechanisms. These studies provide the first direct evidence for active, cholinergically mediated vasodilation during exercise in humans. PMID- 2924414 TI - Cardiac norepinephrine kinetics in hypertrophic cardiomyopathy. AB - We examined the uptake and release of norepinephrine in the cardiac circulation and other regional vascular beds in 11 patients with hypertrophic cardiomyopathy (HCM) and in 10 control subjects during simultaneous infusion of tracer-labeled norepinephrine and isoproterenol. Cardiac neuronal uptake of norepinephrine was assessed by comparing regional removal of tracer-labeled norepinephrine with that of tracer-labeled isoproterenol (which is not a substrate for neuronal uptake) and by the relation between production of dihydroxyphenylglycol (DHPG), an exclusively intraneuronal metabolite of norepinephrine, and regional spillover of norepinephrine. Cardiac extraction of norepinephrine averaged 59 +/- 17% in the patients with HCM, significantly less than in the control subjects (79 +/- 13%, p less than 0.05), whereas cardiac extraction of isoproterenol was similar in the two groups (13 +/- 23% versus 13 +/- 14%), indicating that neuronal uptake of norepinephrine was decreased in the patients with HCM. The cardiac arteriovenous difference in norepinephrine was significantly larger in the patients with HCM than in the control subjects (73 +/- 77 versus 13 +/- 50 pg/ml, p less than 0.05), as was the product of the arteriovenous difference in norepinephrine and coronary blood flow (7.3 +/- 7.3 versus 0.8 +/- 3.0 ng/min, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2924415 TI - Functional abnormalities in isolated left bundle branch block. The effect of interventricular asynchrony. AB - Eighteen patients with isolated left bundle branch block (LBBB) were compared with 10 normal control subjects. Apexcardiograms, phonocardiograms, electrocardiograms, two-dimensional and dual M-mode echocardiograms, and radionuclide ventriculograms (RNV) were performed. There were no differences in the timing of right ventricular events between LBBB and normal subjects; however, striking delays in left ventricular systolic and diastolic events were apparent in the LBBB group. The delay was associated with shortening of left ventricular diastole and resultant increase in the ratio of right to left ventricular diastolic time in LBBB (1.2 +/- 0.08) compared with normal (1.0 +/- 0.06), p less than 0.0001. First heart sound (S1) amplitude, expressed as the ratio S1/S2, was decreased in LBBB compared with normal (0.67 +/- 0.2 compared with 1.34 +/- 0.25, p less than 0.01), in part due to wide separation of the valvular contributors to S1. The abnormal interventricular septal motion in LBBB corresponded to periods of asynchrony in contraction, ejection, end systole, and end diastole between right and left ventricles. Radionuclide ventriculograms revealed decreased regional ejection fraction of the septum in LBBB (40 +/- 16%) compared with 67 +/ 7% in normal subjects (p less than 0.001), while the apical and lateral regional ejection fractions were similar in the two groups. This loss of septal contribution resulted in a reduction in global ejection fraction in LBBB compared to normals (54 +/- 7% compared with 62 +/- 5%, p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2924416 TI - Arterial hemodynamic indexes in Marfan's syndrome. AB - Aortic impedance, wave reflection magnitude, and compliance were measured in patients with Marfan's syndrome during diagnostic cardiac catheterization. Impedance and wave reflections were calculated from standard Fourier series analysis of ascending aorta micromanometer pressure and electromagnetic flow records. Compliance was estimated by a method recently proposed that uses the area under the pressure-time curve assuming a two-element Windkessel model of the circulation. Measurements were made in the baseline state, during vasodilatation with nitroprusside, after beta-adrenergic receptor blockade with intravenous propranolol, and during vasodilatation after beta-blockade. Marfan's syndrome produces alterations from normal in some hemodynamic variables: during baseline conditions, the magnitude of wave reflection was higher than in normal patients. This was normalized by vasodilatation and further increased by beta-blockade. Despite the greatly dilated aortic root, the aortic characteristic impedance was in the normal range, suggesting increased aortic wall stiffness. The baseline total arterial compliance was greatly increased with nitroprusside and was reduced by beta-blockade. beta-Blockade did not decrease the maximum acceleration of blood into the ascending aorta. These are the first detailed measurements of hemodynamic indexes in this disease. The results suggest that acute beta-blockade is not necessarily beneficial in reducing hemodynamic loading on an already dilated aortic root. PMID- 2924417 TI - Noninvasive evaluation of pulmonary artery pressure during exercise by saline enhanced Doppler echocardiography in chronic pulmonary disease. AB - To determine the feasibility of noninvasive determination of right ventricular systolic pressure (RVSP) during a graded-exercise protocol, saline contrast enhanced Doppler echocardiography of tricuspid insufficiency was performed in 36 patients with chronic lung disease and 12 normal controls. In the patients with chronic pulmonary disease, symptom-limited, incremental supine bicycle exercise and pulse oximetry were performed on and off high-flow oxygen. Technically adequate Doppler studies were initially obtained in 20 patients (56%) at rest and 14 (39%) on exercise; these numbers increased to 33 (92%) and 32 (89%), respectively, after enhancement with agitated saline (both p less than 0.001). In 10 patients with chronic lung disease who had simultaneous hemodynamic monitoring during exercise, the correlation between Doppler and catheter measurements of pulmonary artery systolic pressure was close (r = 0.98). Among controls, RVSP increased from 22 +/- 4 at rest (mean +/- SD) to 31 +/- 7 mm Hg at peak exercise. In patients with chronic lung disease, RVSP increased from 46 +/- 20 to 83 +/- 30 mm Hg (both p less than 0.001 vs. controls). Despite normal resting values for RVSP in 28% of study patients, nearly all showed abnormal increases in RVSP during supine bicycle exercise. Increases in RVSP during exercise were greatest in patients who showed oxyhemoglobin desaturation. The short-term administration of oxygen significantly blunted the increase in RVSP during exercise. Saline contrast-enhanced Doppler evaluation of tricuspid insufficiency seems a potentially valuable noninvasive method of determining the exercise response of RVSP in patients with chronic pulmonary disease. PMID- 2924418 TI - Reperfusion alters the relation between blood flow and the remaining myocardial infarction. AB - This study evaluated whether or not reperfusion of ischemic myocardium 2 hours after occlusion alters the basic relation between myocardial blood flow and infarction occurring during permanent occlusion. Awake mongrel dogs chronically instrumented with proximal circumflex coronary occluders were subjected to permanent occlusion (group A, n = 10) or occlusion followed by reperfusion 2 hours later (group B, n = 11). Myocardial blood flow was quantified with radioactive microsphere injections before, 6 hours after occlusion (group A), immediately before release, and 4 hours after reperfusion (group B). Three days later, the dogs were killed, and the heart was sectioned systematically into approximately 80 1-2-g circumferential and transmural samples for radioactive counting and histologic infarct quantification. Epimyocardial and endomyocardial samples from the permanent occlusion group (A) and the reperfused group (B) were separated by infarct range and related to regional myocardial blood flow measurements. In groups A and B, regional myocardial blood flow in endomyocardial and epimyocardial layers were inversely related to the extent of infarction. For given degrees of infarction, myocardial blood flow was significantly higher (greater than twofold) in the reperfused group. Myocardial samples with extensive infarction (51-75%) showed only mild (20-30%) reductions in blood flow when compared with nonischemic regions in the reperfused group. Thus, although early reperfusion may salvage ischemic myocardium, these studies showed that reperfusion causes a new relation between blood flow to the ischemic region and eventual histologic infarct size. When myocardial blood flow is used as an index of myocardial salvage after reperfusion, the basic relation obtained from permanent occlusion studies substantially overestimates the extent of myocardial salvage and underestimates the degree of remaining infarction. PMID- 2924419 TI - Tissue acidosis: role in sustained arteriolar dilatation distal to a coronary stenosis. AB - This study tested the hypothesis that myocardial tissue acidosis is responsible for maintenance of reduced arteriolar tone distal to a severe coronary arterial stenosis. Domestic swine (n = 10) were instrumented with a coronary arterial stenosis that reduced vessel diameter 80%. Measurements of hemodynamic indexes were made 1) before stenosis, 2) at 5, 20, and 60 minutes after stenosis placement, and 3) after each of three, 20-minute NaOH infusions (0.05 M, 0.1 M, and 0.5 M) distal to the stenosis (group 1). Intracellular pH at the end of 30 minutes of 0.5 M NaOH infusion distal to the stenosis was measured in a second group (n = 6) of swine (group 2). After stenosis placement in group 1, endocardial blood flow declined significantly, and evidence of regional acidosis (increased coronary venous Pco2 and decreased coronary venous pH) and ischemia (lactate production) developed. One hour later, evidence of acidosis persisted, though to a lesser extent. Myocardial oxygen and lactate metabolism exhibited similar patterns. Infusion of 0.5 M NaOH (0.38 ml/min) reduced (p less than 0.01) distal zone epicardial blood flow but did not change endocardial flow. Regional myocardial oxygen extraction (75 +/- 8%, mean +/- SD) and consumption (8.2 +/- 2.3 ml/min/100 g) also declined significantly (p less than 0.01) in response to 0.5 M NaOH infusion compared with 60 minutes after stenosis (86 +/- 4 and 12.4 +/ 2.8 ml/min/100 g respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2924420 TI - Rate-related electrophysiologic effects of long-term administration of amiodarone on canine ventricular myocardium in vivo. AB - The electrophysiologic effects of amiodarone were examined in 13 dogs that received 30 g amiodarone orally during 3 weeks and compared with 13 control dogs that did not receive amiodarone. Longitudinal and transverse epicardial conduction velocities were estimated with a square array of 64 closely spaced electrodes and a computer-assisted acquisition and analysis system. Amiodarone caused a rate-dependent decrease in conduction velocity with a slightly greater effect in the longitudinal direction of propagation. Rate-related depression of conduction velocity developed rapidly after abrupt shortening of the pacing cycle length; 67% of the change occurred between the first two beats of the rapid train, and little change occurred after the 10th beat. Recovery from use dependent depression of conduction velocity was exponential with a mean time constant of 447 +/- 172 msec in the longitudinal direction and 452 +/- 265 msec in the transverse direction. Repolarization intervals, defined as the interval between the activation time and the repolarization time in the unipolar electrograms, correlated highly with refractory period determinations in the absence and presence of amiodarone at each cycle length tested. The increase in repolarization intervals and refractory periods resulting from amiodarone treatment did not vary with cycle length. Amiodarone treatment also resulted in a significant rate-related reduction in systolic blood pressure. The systolic blood pressure in the group that received amiodarone decreased by a mean of 50 +/- 23% between steady-state pacing cycle lengths of 1,000 and 200 msec, whereas the corresponding decrease in the control group was 21 +/- 32% (p less than 0.05). Plasma and myocardial amiodarone and desethylamiodarone levels were comparable to those observed clinically. We conclude that long-term amiodarone administration causes rate-dependent reductions in conduction velocity and blood pressure and causes rate-independent increases in repolarization intervals. PMID- 2924421 TI - The human factor at the endless frontier. PMID- 2924422 TI - Coronary disease in Japan. PMID- 2924423 TI - Electroencephalography in the early diagnosis of HIV-related subacute encephalitis: analysis of 185 patients. AB - Of subjects with asymptomatic HIV infection or Lymphoadenopathy Syndrome, 185 were studied by means of electroencephalography coupled with computerized spectral analysis and mapping (EEG-CSA). Abnormal EEGs were found in 30 of 118 (25.4%) patients with asymptomatic infection (CDC Group II) and in 20 of 67 (29.9%) patients with Lymphoadenopathy Syndrome (CDC Group III). The most common EEG abnormalities were represented by theta slowing on the frontal and fronto temporal lobes and, in some cases, by delta slowing and paroxysmal sharp activity on the forebrain. Among 50 patients with abnormal EEGs, 16 showed some abnormalities on neuropsychological testing, whereas mild signs of cerebral atrophy were evident on CT scan in only 12 patients. These findings suggest that EEG-CSA could be a useful and sensitive method in the early detection and monitoring of HIV-related subacute encephalitis. PMID- 2924424 TI - Periodic lateralized epileptiform discharges in acquired immunodeficiency syndrome. AB - A patient with AIDS, who exhibited periodic lateralized epileptiform discharges, is described. The possible implications are discussed. PMID- 2924425 TI - An example of the possible clinical usefulness of topographic EEG displays. AB - This paper shows the brain maps of a patient before and during a seizure initiated by a focus within the right occipital area. The maps demonstrate an ictal transformation in the form of a gradual decrease in frequency of the ictal rhythms, seen also on the EEG traces. However, the maps also show the very distinct difference in the background activity between the left and right hemispheres, and also the possibility of independent foci of depressed activity within the right anterior and posterior temporal areas, the latter not at all evident on the EEG tracings. This case may serve as an example of useful data gathered on a patient by EEG topography, not made clear by a standard recording. PMID- 2924426 TI - Determination of sleep latency in polysomnographic evaluations of daytime somnolence in patients with sleep apnea and patients with narcolepsy. AB - Sleep onset during the multiple sleep latency test was scored by three criteria for 21 patients with narcolepsy and 21 patients with obstructive sleep apnea: a single epoch of stage 1, three consecutive epochs of stage 1, and a single epoch of stage 2 or REM. Mean sleep latency for both groups was predictably shortest using a single epoch of stage 1 and longest using a single epoch of stage 2 or REM. All estimates of sleep latency were highly correlated. It was concluded that a single epoch of any stage of sleep is an appropriate measure of sleep latency for patients with narcolepsy, although a modified scoring system should be developed for patients with sleep apnea. The obstructive apneic episodes prevented or delayed sleep onset on 4.8% to 33.3% of trials depending on the specific criteria used to determine sleep latency. Such apnea-related interruptions to sleep should be taken into account when assessing daytime somnolence in patients with sleep apnea. PMID- 2924427 TI - Fragmented sleep, daytime somnolence and age in narcolepsy. AB - This study examined whether narcoleptics experience an age-related increase in nocturnal sleep disturbance and, if so, what impact that disturbance has on daytime sleepiness. To evaluate these questions, the records of 228 patients diagnosed as narcoleptic were assessed. Total sleep time (TST) and sleep efficiency (SE) significantly decreased, and wake during sleep (WDS), number of awakenings, and percentage of stage one significantly increased across the decades. This indicates an age-related elevation in sleep fragmentation. Daytime sleepiness, however, did not exhibit age effects. These data further support the theory that narcolepsy is a basic neural defect not confounded by excessive daytime sleepiness secondary to sleep fragmentation. PMID- 2924428 TI - Predictive value of electroencephalography for electroconvulsive therapy. AB - The EEG has been a widely-used screening procedure before ECT. Previous studies have correlated seizures and post-ECT slowing with ECT efficacy. We investigated the utility of pre-ECT EEG in predicting therapeutic response and post-ECT confusion. EEGs were normal in 54 of 100 patients undergoing first courses of ECT for refractory depression. Patterns within the normal range, were present in 26/100 while 2/100 had paroxysmal discharges without clinical evidence of epilepsy. Focal and generalized EEG slowing were each present in 9/100 records. Full recovery occurred after ECT in 66.6 per cent of those with normal pre-ECT records, 61.5 per cent with borderline EEGs, 55.5 per cent of patients with diffuse EEG slowing, and 22.2 of cases with focal slow waves. Of those with EEG slowing 22.2 percent had little or no response to ECT as compared to 19.2 per cent with EEGs within normal limits and 9.3 per cent with normal EEGs. Four of 6 patients with prolonged confusion had normal EEGs, while 1 each had focal and generalized slowing. EEG slowing was related to incomplete ECT response, but not to therapeutic failure or post-ECT confusion. The limited predictive power of pre ECT EEG may reflect the prevalence of normal or nonspecifically abnormal EEGs in psychiatric patients and the general efficacy of ECT. Other neurophysiologic methods may yield more definitive information about the mechanism and use of ECT. PMID- 2924429 TI - Emery-Dreifuss syndrome and X-linked muscular dystrophy with contractures: evidence for homogeneity. AB - We report on a family in which individuals have clinical features of both Emery Dreifuss syndrome (EMD) and X-linked muscular dystrophy with contractures (XLMDC). Molecular studies on this kindred showed linkage between the disorder and probe DXS 52 (St14) located at Xq28. The gene for conventional EMD has previously been mapped to this region and our molecular findings therefore suggest that EMD and XLMDC represent the phenotypic spectrum of the same mutated gene rather than heterogeneity, as sometimes postulated. PMID- 2924430 TI - Childhood manifestation of autosomal dominant polycystic kidney disease: no evidence for genetic heterogeneity. AB - Autosomal dominant polycystic kidney disease (ADPKD) usually becomes symptomatic between the third and fifth decades. We studied ten families segregating for ADPKD in which children were observed with typical manifestations of the disease at birth or in early childhood. In these families, linkage analysis was carried out with a cloned DNA sequence from the alpha-globin locus known to be closely linked to the disease gene in adult onset ADPKD. In the families studied here, close linkage (theta max = 0.09 at zmax = 2.32) was also observed between the marker and disease loci. These results provide no evidence for genetic heterogeneity of ADPKD in families with early and adult onset. PMID- 2924431 TI - Growth, bone maturation and pubertal development in children with the EMG syndrome. AB - In 7 patients (5 girls, 2 boys) with the EMG or Wiedemann-Beckwith syndrome, statural growth, bone age (BA), weight and pubertal development were studied longitudinally. Height was above the 90th percentile (%) for chronological age (CA) after age 2 years, reaching an average of 2.5 SD above the mean at or after puberty. Adult or attained height also exceeded significantly (P less than 0.015) parental (genetic) target height by 13.2 cm on the average. In one girl, adult height prognosis (190 cm) could be reduced to an adult height of 183 cm by high dose estrogen treatment. In most children, growth velocity remained above the 90th % up to 4-6 years of age and normalized thereafter. In all patients studied, bone age was markedly advanced and particularly so during the first 4 years after birth. Weight was above the 90th-97th % during infancy and early childhood and remained there, appropriate or slightly subnormal for height, until adulthood, except for 3 girls who reached and maintained the 50th % during or after puberty. Spontaneous pubertal development occurred within normal limits for CA and around the 50th % for BA. Except for the marked bone age acceleration, the reason for the increased statural growth and adult height in patients with the EMG syndrome is still unknown. PMID- 2924432 TI - A case of prenatal diagnosis of a familial satellited Yq chromosome. AB - A case of a fetus with a satellited Yq revealed during prenatal diagnosis because of advanced maternal age is presented. This case is the 18th reported in the literature. Cytogenetic studies in the father, uncle and grandfather of the fetus revealed that the Yqs was inherited and the possible mechanisms of origin are discussed. PMID- 2924433 TI - Neural tube defects and omphalocele in trisomy 18. PMID- 2924434 TI - "Unstable" translocation not proven unstable. PMID- 2924435 TI - Immune adherence and the processing of soluble complement-fixing antibody/DNA immune complexes in mice. AB - We have examined in mice the immune adherence (IA) reactivity and the fate (clearance kinetics and organ distribution) of a variety of preformed and nascent soluble antibody/125I-DNA immune complexes prepared at antibody excess. Parallel studies of the clearance kinetics and organ deposition of free DNA were also conducted. Preformed immune complexes prepared with large dsDNA bound to mouse platelets in vivo and exhibited clearance kinetics in general agreement with our previous observations in rabbits. Very little kidney deposition was evident for these immune complexes, but three to four times as many counts were found in the kidneys when free DNA was injected. Nascent immune complexes did form in the circulation, but in contradistinction to our previous studies of nascent immune complexes in rabbits and rhesus monkeys, these immune complexes did not demonstrate IA and had clearance kinetics and organ distributions intermediate between the preformed immune complexes and free DNA. Thus, complement-fixing antibody/DNA immune complexes that could form in the circulation might be cleared both via immune complex recognition mechanisms and via DNA recognition mechanisms. The role of IA in modulating the organ deposition of complement fixing immune complexes is also discussed. PMID- 2924436 TI - Immunocytochemical characterization of lymphocyte development in human embryonic and fetal livers. AB - Lymphohemopoietic progenitor cells and the development of lymphocytes in human embryonic and fetal livers during the 4 to 11 weeks of gestation were examined immunocytochemically by using a panel of monoclonal antibodies. CD9+, CD10+, CD19+, and CD20+ cells of B cell lineage became detectable from the 8th gestational week. CD2+ and CD3+ cells of T cell lineage were observed from the 10th gestational week. Tdt+ cells first appeared on the 43rd day of gestation. Both CD34+ and Ia+ cells were observed in all examined livers, and these cells appeared morphologically as small lymphoid cells from the 43rd day of gestation. These seemed to suggest that B lymphocytes developed in fetal liver from 8 weeks of gestation and lymphohemopoietic progenitor cells were comprised in Tdt+ cells in liver during the 43rd to 56th day of gestation. PMID- 2924437 TI - Up-regulation of natural killer activity of human immunodeficiency virus-infected patients by in vitro-differentiated macrophages. AB - Patients with acquired immunodeficiency syndrome (AIDS)-related complex and asymptomatic individuals seropositive for human immunodeficiency virus (HIV) have depressed natural killer (NK) activity. Normal human macrophages cultured for 3-7 days significantly up-regulated the NK activity of mononuclear cells obtained from the blood of asymptomatic HIV-seropositive individuals and patients with AIDS. Following a 4-hr incubation of patients' cells with in vitro-differentiated macrophages, the greatest augmentation of NK activity was seen in asymptomatic HIV-seropositive individuals who were receiving treatment with azidothymidine. Stimulation of macrophage immunoregulatory activities or adoptive immunotherapy with ex vivo-activated monocytes may be beneficial in HIV-infected patients. PMID- 2924438 TI - Serum IgG subclass levels in patients with primary immunodeficiency syndromes or abnormal susceptibility to infections. AB - Serum IgG subclass levels were measured using an indirect competitive immunoenzymatic assay with monoclonal antibodies in 221 patients affected with definite immunodeficiency (ID) syndromes and 229 patients presenting with infection patterns suggestive of ID, but with normal immunoglobulin class levels and no clear evidence of ID. In common variable ID and IgG-IgA deficiency with normal or high IgM, subclass imbalance (mostly IgG1-IgG3 or IgG2-IgG4 deficiency) was the rule, with a higher incidence of severe infections in IgG2-IgG4 defects. One-fifth of patients with IgA deficiency, especially those with autoimmune cytopenia, had subclass deficiencies with no significant correlation with the occurrence of infections. Subclass (mostly IgG2-IgG4) deficiencies were also observed in severe combined ID, defective expression of HLA class II antigens, chronic mucocutaneous candidiasis, and IgM deficiency. Subclass levels were normal in all but one (who was IgG3 deficient) patient with the Wiskott-Aldrich syndrome and in the Buckley's syndrome, except for an unusual patient who presented with low IgG and IgA levels. Subclass (mainly IgG2) deficiency occurred in 24% of infected patients without known ID. PMID- 2924439 TI - Simultaneous use of multiple serologic tests in assessing clinical activity in systemic lupus erythematosus. AB - Ten technics for quantifying and qualifying anti-DNA antibodies were correlated with manifestations of disease activity in sera from 27 patients with systemic lupus erythematosus (SLE) using both a simple and a stepwise regression. In the stepwise analysis, a panel consisting of four of these tests provided maximal correlation (r = 0.68) with clinical status. Low IgM anti-DNA was a significant correlate of nephritis in stepwise discriminant function analysis. Multivariate analysis can offer distinct advantages over simple correlation in understanding the role of serological abnormalities in disease expression in SLE. PMID- 2924440 TI - Vanderbilt University's Bridge Program: the commitment that worked. PMID- 2924441 TI - Echocardiographic abnormalities in chronic asymptomatic alcoholics. AB - Alcohol abuse is a frequent contributor to elevated blood pressure, but the literature is ambiguous about the role of hypertension in producing left ventricular dysfunction. Fifty asymptomatic male alcoholics admitted for detoxification were studied using echocardiograms and systolic time intervals. Alcoholics were separated into Group I (28 with hypertension) and Group II (22 without hypertension). Forty-four patients had analyzable echocardiograms and were compared to 29 nonalcoholics. Group III consisted of 14 nonalcoholics with hypertension. Group IV consisted of 15 normotensive nonalcoholics (controls). The ejection fraction and shortening fraction were reduced in Group I (p less than 0.05). Hypertensive alcoholics had increased left ventricular mass indices but less than hypertensive nonalcoholics. Left ventricular wall stress was compared to mass as an index of ventricular compensation. The wall stress to mass index for hypertensive alcoholics was 1.65 as compared to 1.43 for the controls. Alcoholics without hypertension had a wall stress to mass ratio of 1.54. Hypertensive patients had a reduced wall stress to mass ratio of 1.38 when compared to controls. These data suggest an inappropriate compensatory response to afterload. Alcohol and hypertension combined may be more harmful to left ventricular function than either disease alone. PMID- 2924442 TI - Diastolic atrioventricular valve closure and regurgitation following atrial contraction: their relation to timing of atrial contraction. AB - Some authors have proposed that atrial contraction per se is able to close the atrioventricular (AV) valves. To determine whether tight closure of the AV valves can be accomplished solely by atrial contraction, the existence of diastolic regurgitation following atrial contraction and its relation to the PQ interval were examined in 13 patients with AV block (2 of the first degree, 4 of the second degree, and 7 of the third degree), using pulsed Doppler echocardiography, which allowed noninvasive estimation of valvular regurgitation in the physiological state. Diastolic mitral and tricuspid regurgitations were detected in the left and right atria near the respective AV valves in all 13 patients despite different degrees of AV block, while these valves were observed to be in apparently closed position during regurgitation on the two-dimensional and M-mode echocardiograms. The duration of regurgitant signals was prolonged with an increase in the PQ interval in the electrocardiogram, but it became short again as the P wave approached the preceding rapid filling wave. These results suggest that atrial contraction may initiate the closure of the AV valves but is not capable of closing the valves tightly, and atrial contraction with long PQ interval may contribute little to augmentation of cardiac output in patients with AV block. PMID- 2924443 TI - Temporary pacing catheter placement in patients requiring continuous external pacing. AB - Electrocardiographic features of temporary transvenous pacemaker have been discussed and have been used to guide insertion of pacemaker without fluoroscopic aid. The following is a description of the electrocardiographic features of temporary endocardial pacemaker insertion in a patient who is chronically dependent on external temporary transthoracic pacing. PMID- 2924444 TI - Acute myocardial infarction due to coronary spasm associated with L-thyroxine therapy. AB - A 63-year-old man with hypothyroidism is described. He had been receiving L thyroxine therapy following mitral valve surgery. About three weeks into the therapy regimen, he complained of severe retrosternal chest oppression. Electrocardiographic findings and laboratory data indicated a diagnosis of acute myocardial infarction due to the L-thyroxine therapy. Emergency selective coronary angiography was performed. Comparing his coronary angiograms with those obtained before surgery indicated a severely spastic left coronary artery. We believe this is the first report of myocardial infarction due to coronary spasm, demonstrated by angiography associated with L-thyroxine therapy. PMID- 2924445 TI - A rare case of recurrent vasodepressive attacks of 2-hours duration: analysis of the mechanism by muscle sympathetic nerve activity recording. AB - Muscle sympathetic nerve activity was recorded in a 57-year-old male patient suffering from severe hypotensive attacks with bradycardia for 10 years. Continuous blood pressure recording demonstrated frequent drastic falls in pressure. Disappearance and reappearance of muscle sympathetic nerve activity coincided with the onset and termination of attacks. Awakening from sleep or emotional and/or cardiovascular stress seems to trigger hypotension. Cardiac pacemaker was not useful in limiting the attack, because right ventricular pacing caused abrupt falls in both blood pressure and heart rate. PMID- 2924446 TI - The relationship between lymphogenous and hematogenous metastasis in rats bearing the MT-100-TC mammary carcinoma. AB - Temporal and quantitative aspects of lymphogenous and hematogenous metastasis were examined using the rat MT-100-TC mammary carcinoma injected into the hind feet of syngeneic rats. Metastases first appeared in the draining popliteal nodes and then progressed in an invariable pattern to regional and then distal nodes: 'skipped' negative nodes within a chain of positive nodes were not observed. Metastatic progression in the lymphatic system occurred metachronously, with nodal metastases acting as 'generalizing' sites for 'downstream' nodes. Perturbation of lymph flow was apparent when nodes were involved with tumor, and resulted in retrograde seeding of contralateral nodes. Lung involvement was first observed by ectopic bioassay in 50 per cent of animals after 1 and 2 weeks of primary tumor growth; in contrast, all animals had popliteal involvement after 1 week. These results indicate that lymph nodes and lungs are not seeded synchronously, and the lungs are seeded after nodal metastases. Thus, a phase of metastasis has been identified, during which resection of the primary tumor and local nodes may well be curative in the 50 per cent of cases in which the disease is confined to these sites. PMID- 2924447 TI - The flavonoid tangeretin inhibits invasion of MO4 mouse cells into embryonic chick heart in vitro. AB - Tangeretin, a flavonoid from citrus plants, was found to inhibit the invasion of MO4 cells (Kirsten murine sarcoma virus transformed fetal mouse cells) into embryonic chick heart fragments in vitro. The flavonoid appeared to be chemically stable in tissue culture medium, and the anti-invasive effect was reversible on omission of the molecule from the medium. Unlike (+)-catechin, another anti invasive flavonoid, tangeretin bound poorly to extracellular matrix. It did not alter fucosylated surface glycopeptides of MO4 cells. Tangeretin seemed not to act as a microtubule inhibitor, as immunocytochemistry revealed no disturbance of the cytoplasmic microtubule complex. However, at anti-invasive concentrations of tangeretin, cell proliferation and thymidine incorporation appeared to be inhibited. When cultured on an artificial substrate, treated MO4 cells were less elongated, covered a larger surface area and exhibited a slower directional migration than untreated cells. From the decrease in ATP content in MO4 cells after tangeretin treatment, we deduce that this flavonoid inhibits a number of intracellular processes, which leads to an inhibition of cell motility and hence of invasion. PMID- 2924448 TI - Low-molecular-weight membrane component inhibits the metastatic phenotype of B16 F10 melanoma. AB - Treatment of the metastatic melanoma cell lines B16-F1 and B16-F10 with 1.5-2 per cent butanol elevates their experimental metastatic potential, whereas reconstitution of butanol-extracted B16 cells with crude butanol extracts decreases the number of experimentally induced lung foci. We partially purified the biologically active components from crude butanol extracts of B16-F1 by high performance liquid chromatography and isoelectric focusing, and found the inhibitory activity (i) was in the low-molecular-weight (5-10 kDa) fraction of the chromatogram, (ii) had an isoelectric pH between 5.6 and 5.8, (iii) was distinct from a thiol-protease activity eluted from the isoelectric focusing bed at pH 4.9-5.3 and (iv) was not itself an inhibitor of serine or thiol proteases. Incubation of butanol-extracted B16-F10 cells with known inhibitors of serine, acid and thiol protease inhibitors had no effect on the experimental metastatic phenotype. Although the apparent molecular weight was low, the inhibitor(s) tended to aggregate after focusing, probably owing to the presence of carrier ampholines. Using two-dimensional gel electrophoresis, we observed slight differences between intact and butanol-extracted cells, most of them in the low molecular-weight region. These results suggest that butanol treatment may reversibly release certain inhibitors of cell surface enzymes other than proteases, which might be involved in invasion and metastasis. PMID- 2924449 TI - Changes in the tumorigenic and metastatic properties of murine melanoma cells treated with a triazene derivative. AB - Treatment of B16/BL6 murine melanoma cells in vitro with the 'xenogenizing' agent potassium p-(3-methyl-1-triazeno)benzoate (MM-COOK) had a profound impact on the tumorigenic and metastatic properties of the tumor, an effect that was only detectable in immunologically intact hosts. The treated tumor cells gave rise to a considerably smaller number of experimental and spontaneous pulmonary metastases and displayed an impaired growth rate in vivo, but were highly tumorigenic and metastatic in irradiated recipients. Moreover, the drug-treated cells retained the in vitro growth pattern and plating efficiency of the parent line, and were able actively to immunize intact hosts. Studies aimed at clarifying the mechanisms responsible for the decreased metastatic potential of the cells treated with MM-COOK indicated the involvement of host immune responses largely mediated by cells in the T-dependent compartment with no major contribution of natural immunity effector mechanisms. PMID- 2924450 TI - Tumor cell adhesion to frozen lymph node sections--an in vitro correlate of lymphatic metastasis. AB - Two variant sublines of the murine 3LL carcinoma with divergent potentials for lymphatic metastasis were used to assess the relationship between tumor cell potential for lymphatic metastasis and its ability to adhere specifically to lymphatic tissue. Using fresh cryostat sections of lymph nodes and spleens, it was found that tumor cell adhesion to the lymphatic tissue but not to control sections of the brain correlated well with their ability to metastasize lymphatically. On the other hand, there was no correlation between tumor cell attachment to isolated lymphocytes in vitro and their potential for lymphatic metastasis. When tumor cells were pretreated enzymatically or with the metabolic inhibitor tunicamycin with the aim of modulating cell surface carbohydrates, adhesion to the lymph node sections could be significantly reduced, implicating cell surface glycoproteins and in particular galactosyl groups in the binding. The results suggest that tumor cell attachment to lymph node cryostat sections could provide a useful tool in the study of host-tumor interactions in lymphatic metastasis. PMID- 2924451 TI - Effects of laminin on the attachment of glioma cells to type IV collagen. AB - The interaction of tumour cells with basement membrane components is thought to be important in influencing their invasive and metastatic properties. This paper describes the effect of laminin on the attachment of radiolabelled glioma and B16 murine melanoma cells to tissue culture plastic and type IV collagen. With the exception of the non-metastatic B16 F1 variant, laminin (and fibronectin) stimulated cell attachment to tissue culture plastic. Although laminin stimulated the attachment of the B16 BL6 metastatic variant to type IV collagen, it consistently inhibited the attachment of the glioma cells under the same conditions. Laminin appeared to exert its effect by adsorption to the collagen and was not cytotoxic to the glioma cells. In contrast, fibronectin had very little effect on cell attachment to type IV collagen. One of the most unusual features of glioma is the rarity of metastasis to extraneural sites. However, the effect of laminin observed here may not be the only factor involved in the metastatic inefficiency of this tumour type. PMID- 2924452 TI - Restored invasion of mouse MO4 cells into chick heart in vitro through mutual conditioning at reduced temperature. AB - Invasion of malignant mouse MO4 cells into embryonic chick heart fragments in confronting organ cultures was arrested for 7 days when the temperature of incubation was lowered to 28 degrees C. Afterwards invasion resumed and progression between days 10 and 17 at 28 degrees C was comparable to that between days 0 and 7 at 37 degrees C. This pattern of progression of MO4 cell invasion at 28 degrees C was unaltered when either MO4 cells or heart fragments or both were preincubated separately at 28 degrees C for 14 days before confrontation with each other. Invasion at 28 degrees C resumed only when MO4 cells and heart tissue had been in immediate contact for at least 7 days. Metabolic labelling with [3H]fucose showed a correlation in time between transient suppression of invasion and transient inhibition of incorporation of fucosylation-precursor molecules into glycoproteins by MO4 cells. The latter activity was far less temperature sensitive in heart cells. Our observations suggest that metabolic cooperation between invading MO4 cells and heart tissue is essential for progression of invasion in vitro. PMID- 2924453 TI - Loss of spontaneous metastasizing potential in mouse mammary tumors. AB - Among 25 C3H/He and C3Hf/He spontaneous mammary tumors that all had produced pulmonary metastases in the autochthonous mice, and also produced pulmonary metastases during subsequent sequential syngeneic intramammary passages, three were observed to stop producing metastases. The specific investigation of the observed changes in behavior is described. When the tumors were re-started in serial intramammary passage from early, cryopreserved transplant generations, the loss of metastasizing potential reoccurred in the same, or in nearly the same, transplant generations. In one tumor from which three transplant lines had been established, the metastasizing potential was lost in all transplant lines during closely related transplant generations. It seems that a spontaneous reduction of malignant behavior in mouse mammary tumors may be an occasional neoplastic characteristic, and that the observed losses of metastasizing potential may have been determined by a programmed genetic change. PMID- 2924454 TI - The histology of distraction osteogenesis using different external fixators. AB - The local biology of distraction osteogenesis using Ilizarov and Wagner external fixators was compared in unilateral tibial lengthenings in two groups of eight dogs. Serial roentgenograms with histological correlation revealed some basic similarities as well as distinct differences between the two groups. All dogs fully bridged the experimental gap by intramembranous ossification. Subtle histological changes in the alignment of collagen bundles and subsequent ossification reflected the mechanical configuration of each fixator. The multiplanar, full-pin Ilizarov system delivered concentric load to the site of osteogenesis, inducing perfectly parallel columns of new bone. The uniplanar, one half pin Wagner system induced angulation of the collagen and subsequent bone columns on the basis of eccentric load to the osteogenic interface. Despite a significant difference in axial rigidity, the Ilizarov and Wagner external fixators induced osteogenesis of equal volume. PMID- 2924455 TI - Epiphyseal distraction. Chondrodiatasis. AB - Chondrodiatasis is a limb-lengthening technique involving slow, controlled, symmetric epiphyseal distraction. The clinical and histological differences between this technique and distraction epiphysiolysis are described. Results are given for the elongation of 170 bone segments in 75 children (41 with limb-length discrepancies and 34 with achondroplasia). All patients were operated upon while the growth plate was still open with maximum bone maturation corresponding to Risser 2. PMID- 2924456 TI - Epiphyseal distraction. Hemichondrodiatasis. AB - Hemichondrodiatasis is a technique of closed, gradual, asymmetric distraction of the growth plate to correct angular deformities in growing children. This report describes the technique and the results achieved in 35 operated lower extremity segments, 14 involving the femur and 21 involving the tibia. The best results were achieved in posttraumatic deformities when the bone bridge occupied less than 20%-30% of the epiphyseal plate. The procedure is best performed toward the end of growth, or earlier if a progressive deformity exceeds 15 degrees - 20 degrees. PMID- 2924457 TI - The callotasis method of limb lengthening. AB - Callotasis is a lengthening technique that involves slow, controlled distraction after subperiosteal-submetaphyseal osteotomy. The technique and its advantages over other methods are described. Results of lengthenings involving 270 operated bone segments (146 femurs and 124 tibias) in 140 patients are reviewed. Ninety five patients had limb-length inequality and 45 had hypochondroplasia or achondroplasia. On average, 6.6 cm, or 24.6% of initial length, was gained. The mean healing index was 39; the complication rate was 13.3%. PMID- 2924458 TI - Ilizarov treatment of tibial nonunions with bone loss. AB - Twenty-five patients aged 19-62 years were treated for tibial nonunions (22 atrophic, three hypertrophic) with bone loss (1-23 cm, mean 6.2 cm) by the Ilizarov technique and fixator. Thirteen had chronic osteomyelitis, 19 had a limb length discrepancy (2-11 cm), 12 had a bony defect (1-16 cm), and 13 had a deformity. Six had a bone defect with no shortening, 13 had shortening with no defect, and six had both a bone defect and shortening. Nonunion, bone defects, limb shortening, and deformity can all be addressed simultaneously with the Ilizarov apparatus. Bone defects were closed from within without bone grafts by the Ilizarov bone transport technique of sliding a bone fragment internally, producing distraction osteogenesis behind it until the defect is bridged (internal lengthening). Length was reestablished by distraction of a percutaneous corticotomy or through compression and subsequent distraction of the pseudarthrosis site (external lengthening). Distraction osteogenesis resulting from both processes obviated the need for a bone graft in every case. Deformity was corrected by means of hinges on the apparatus. Infection was treated by radical resection of the necrotic bone and internal lengthening to regenerate the excised bone. Union was achieved in all cases. The mean time to union was 13.6 months, but it was only 10.6 months if the time taken for unsuccessful compression-distraction of the nonunion is eliminated from the calculation. The bone results were excellent in 18 cases, good in five, and fair in two based on union in all cases, persistent infection in three, deformity in four, and limb shortening in one. The functional results were excellent in 16 cases, good in seven, fair in one, and poor in one based on return to work and daily activities in all cases, limp in four cases, equinus deformity in five cases, dystrophy in four cases, pain in four cases, and voluntary amputation for neurogenic pain in one case. PMID- 2924459 TI - Correction of complicated extremity deformities by external fixation. AB - Thirty-three limb segments with various deformities in 28 children were treated by external fixation. Sole bone lengthenings and trauma cases were excluded from this study. The Wagner device was used in six cases, the Ilizarov ring fixator in seven, and the Orthofix in 20. Indications, techniques, results, and complications are discussed. The results indicate that modern external fixation is an effective alternative method in the treatment of problem cases such as congenital pseudarthroses, severe relapsed or neglected clubfoot, high dislocated hips, and limb deformities with length discrepancies. PMID- 2924460 TI - Atlantoaxial instability and neurologic indicators in rheumatoid arthritis. AB - Atlantoaxial subluxation in rheumatoid arthritis is characterized by pain, disability, and occasionally death. Surgical fusion of the offending vertebrae is the appropriate surgical remedy, but it is a procedure with a high failure and complication rate. Because cord compression and myelopathy are the main complications of this condition, it would be logical to use evidence of early neurologic deficit as an indicator for surgery. A group of 250 patients with rheumatoid arthritis were investigated to evaluate the neurologic status with respect to the degree of instability in the proximal cervical spine. Neurologic isolated signs such as hyperreflexia could not be correlated with the onset of cervical myelopathy or quadraparesis or to the radiographically measured degree of atlantoaxial instability. These signs should not be used as an indication for surgery. The positive indications are intractable pain, cervical myelopathy, and severe atlantoaxial instability. PMID- 2924461 TI - Threaded cup acetabuloplasty. Early clinical experience. AB - Loosening of the acetabular cup component in total hip arthroplasty (THA) remains a source of ongoing concern. Threaded cup acetabuloplasty (TCA) utilizes torque and compression to gain purchase of the acetabular cup into the bony margin of the acetabulum. In an earlier study of 121 patients who had THA with TCA, patient assessments and roentgenograms were examined at an average of 30 months after surgery. Twenty percent of the cases were carried out for failed arthroplasty and 20% of the procedures required bone-graft reconstruction. A 22% incidence of moderate to severe postoperative pain, a 3% incidence of cup dislodgement, and a 24% incidence of radiolucencies between 1-2 mm were observed. The four cup dislodgements occurred in patients with severe osteopenia or in those requiring extensive bone-graft acetabular reconstruction. Good clinical results were obtained for osteoarthritic patients treated with primary THA. These early findings suggest that there is no advantage, but there are possible disadvantages, to threaded cup acetabuloplasty when compared to cup fixation with cement. PMID- 2924462 TI - Primary osteoarthritis of the hip joint in Japan. AB - Diagnostic criteria for primary osteoarthritis of the hip joint in the Japanese population were determined by the roentgenographic measurements of the center edge (CE) angle, the Sharp angle, and the acetabular roof obliquity in 254 normal hips. Primary osteoarthritis must meet the following conditions: (1) absence of femoral head deformities; (2) a CE angle of Wiberg greater than 19 degrees; (3) a Sharp angle less than 45 degrees; and (4) acetabular roof obliquity less than 15 degrees. These measurements are taken from roentgenograms during the early stage of the disease. Under these criteria, primary osteoarthritis accounted for only 0.65% of 2000 consecutive cases of osteoarthritis. Observation of the natural course of primary osteoarthritis revealed two subtypes. The superolateral type developed from the subset of normal hips with a relatively greater degree of acetabular roof obliquity. PMID- 2924463 TI - Association of preoperative hip motion and sciatic nerve palsy following total hip arthroplasty. AB - This retrospective study investigated the possible correlation between preoperative hip range of motion (ROM) and postoperative sciatic nerve palsy. From 1971 to 1987, 12 patients with partial sciatic nerve palsies subsequent to total hip arthroplasty (THA) without known etiologies were identified. During this same period a random sample of 340 patients with 373 palsy-free THAs were also identified. To exclude possible bias from revision patients (revision procedures are reported to have an increased incidence of postoperative nerve palsies), the patients were divided into three groups: (1) all THAs; (2) primary THAs; and (3) revision THAs. The preoperative hip motions studied were flexion, abduction, adduction, internal rotation, and external rotation. Analysis of the data showed no correlation between limited ROM preoperatively and the risk of postoperative nerve palsy for any of the three groups. PMID- 2924464 TI - Temperatures measured during reaming of the femoral neck and head. A preliminary report. AB - Thermal injury is a well-known complication during mechanical manipulation of cortical bone. In order to investigate the magnitude of the problem in relation to cancellous bone, the temperature elevation in the head of the femur during reaming for a sliding screw osteosynthesis was measured in ten patients. Temperatures in excess of 50 degrees for a duration of more than one minute were found within approximately 2 mm from the periphery of the reamer. This finding implies that the thread of the screw will be placed in an osteonecrotic zone. PMID- 2924465 TI - The patellar clunk syndrome. A complication of posterior stabilized total knee arthroplasty. AB - Patellofemoral pain due to an unusual suprapatellar fibrous nodule developed in three patients after posterior stabilized total knee arthroplasty. Each patient had a "catch" or "clunk" associated with pain on extension of the knee. At revision, a prominent fibrous nodule was found at the junction of the proximal patellar pole and the quadriceps tendon. The pathogenesis of this proximal fibrous nodule may involve impingement of the anterosuperior edge of the intercondylar notch area of the femoral component into the proximal quadriceps tendon or may involve impingement of the patellar prosthesis itself on the quadriceps tendon. Roentgenographic examination revealed an abnormally proximal placement of the patellar prosthesis on the patella. Surgical removal of the fibrous nodule resolved the symptoms. Revision of the patellar prosthesis may be necessary. PMID- 2924466 TI - Arthroscopy in acute septic knees. Management in pediatric patients. AB - Arthroscopic evacuation, debridement, and irrigation of acute septic knees in children were effective adjuncts in the treatment of this joint infection. Sixteen knees in 16 pediatric patients were treated with arthroscopic management. Ninety-four percent of the knees had sepsis secondary to Staphylococcus aureus. Two immune-suppressed patients (postrenal transplants) had combined S. aureus and Pseudomonas aeruginosa infections. Twenty-five percent of the patients had a foreign body in the joint that was removed arthroscopically. No postoperative irrigation or drainage systems were used. At an average follow-up period of three years, no evidence of persistent or recurrent infection was noted. Roentgenograms showed no evidence of joint or epiphyseal destruction. Because of the low morbidity associated with the procedure, rapid restoration of joint motion and patient mobility was seen in all patients. Arthroscopic debridement of acute septic knees may be carried out in pediatric patients, given appropriate equipment and arthroscopic skills. PMID- 2924467 TI - The use of functional knee braces in the control of pathologic anterior knee laxity. AB - Four designs of knee braces, Don-Joy 4 Point, RKS, Lenox Hill, and CTi, were evaluated in 42 patients with a unilateral knee brace. Brace migration was the predominant complaint, as noted in patient questionnaires. All braces tested reduced giving-way episodes (34 of 42 patients reported no giving way during brace usage). All four brands of braces reduced the grade of pivot shift (mean reduction = 0.8 grade). Instrumented laxity testing with the KT-1000 arthrometer was performed with an 89-N passive anterior displacement, high load passive anterior displacement, and a quadriceps contraction active displacement. Brace use decreased the measured pathologic anterior displacement on all tests. During functional testing with one-legged hop and 40-yard shuttle run, the mean values were not significantly changed by brace usage. PMID- 2924468 TI - Supracondylar fracture of the femur after GUEPAR total knee arthroplasty. A new treatment method. AB - A 71-year-old woman incurred an unstable, comminuted supracondylar fracture of the femur above the tip of a GUEPAR prosthesis. The prosthesis was not loose. Immediate open reduction and internal fixation were performed using a segment cut from an intramedullary rod. This provided axial alignment and functioned as an internal stent with stable fixation of the fracture. Supplementary fixation with a plate and screws, cerclage wires, and an autogenous bone graft led to early mobilization, solid bony union, and an excellent functional result. PMID- 2924469 TI - Treatment of open tibial fractures with the Orthofix fixator. AB - External fixation is considered the treatment of choice for severe open tibial fractures. A prospective study was designed to evaluate the use of the Orthofix Dynamic Axial Fixator (DAF) for the short- and long-term treatment of open tibial fractures. Forty-four patients with 45 open tibial fractures were enrolled in the study, which included a one-year follow-up period. Eighty-nine percent of the fractures were classified as Gustilo and Anderson's Type III. All fractures except one were united in a mean healing time of 22.6 weeks. The dynamization of the Orthofix in nonsegmental fractures occurred at an average of 8.1 weeks. Segmental fractures received a two-stage dynamization. The first stage consisted of removing the supplementary pins, once callus formation was seen at one of the fractures lines, plus the addition of a bone graft. This stage occurred at an average of 8.8 weeks. The second stage consisted of unlocking the telescoping rods and allowing dynamic axial loading of the consolidating graft. This stage occurred at an average of 19.0 weeks. The implementation of this one-plane unilateral frame, which is capable of converting from a rigid to a dynamic fixator, combined with a bone graft in 58% of the patients, contributed to a 98% success rate. Proper timing of dynamization is emphasized to avoid angulation, nonunion, or delayed union. PMID- 2924470 TI - Dislocation of the pisiform treated by primary resection. A case report. AB - A case of isolated dislocation of the pisiform occurred in an 18-year-old man who was treated by primary resection and followed for two years. As observed in previous reports, primary resection was a successful treatment. PMID- 2924471 TI - Acute volar compartment syndrome during skeletal traction in distal radius fracture. A case report. AB - Fractures of the distal end of the radius rarely cause acute compartment syndrome of the forearm. Acute compartment syndrome of the forearm occurred after a fracture of the distal end of the radius in a 17-year-old boy who developed symptoms after application of skeletal traction. Satisfactory recovery was obtained by early decompressive fasciotomy. In this case a combination of traction and elevation of the forearm appeared to have increased the susceptibility of the limb to acute compartment syndrome. PMID- 2924472 TI - Intraarticular fractures of the distal humerus. Surgical treatment and results. AB - In a 12-year period, 104 patients with intraarticular fractures of the distal humerus received surgical treatment. Based on the Arbeitsgemeinschaft fur Osteosynthesefragen/Association for the Study of Internal Fixation (AO/ASIF) classification, there were 40 monocondylar fractures, 46 bicondylar fractures, and 18 fractures of the ulnar epicondyle with the fragment dislocated in the elbow joint. In children almost all fixations were done with Kirschner wires. The adult fractures were stabilized according to the recommendations of the AO/ASIF, i.e., monocondylar fractures by screws and/or single-plate fixation and bicondylar fractures by screws and dual-plate fixation, preferably with reconstruction plates. Comminuted fractures required an additional osteotomy of the olecranon. Except for children, the essential feature of postoperative management was early functional treatment by continuous passive motion. Eighty eight patients (84.6%) were followed with an average follow-up time of 4.4 years. The results were evaluated for range of motion, pain, working capacity, neural and vascular impairment, valgus/varus deformity, and subjective judgment. The long-term outcome of almost 81% good and very good results suggests that operative treatment can be valuable when indications, anatomic surgical reconstruction, and postoperative care are performed correctly. PMID- 2924473 TI - Peptostreptococcus magnus does not cause hematogenous infections in experimental arthroplasties. AB - Rabbits with cemented endoprostheses in the knee joints were given 1-ml intravenous injections of suspensions containing Peptostreptococcus magnus (3 x 10(8) colony-forming units/ml) on three consecutive days seven weeks postoperatively. The animals were killed after another seven weeks. The bacterial challenge did not result in infection. This is in contrast to a previous study using the same experimental system with another anaerobic bacterial species, Propionibacterium acnes, which caused infection in approximately 50% of the animals. Both these bacteria have previously been reported to cause late infections in human arthroplasties. The present results may indicate differences in the spreading mechanisms, i.e., that Peptostreptococcus magnus may have a limited ability to cause hematogenic infections and that late infections of endoprostheses by Peptostreptococcus magnus are due to perioperative contamination. PMID- 2924474 TI - Altering local soft-tissue circulation fails to halt venous drainage from the femur. AB - It has been suggested that tourniquet application proximal to bone biopsy in an extremity can reduce the number of tumor cells spread through circulation. This study investigates the anatomical pathway through which rapid cell spread could occur. Radioactively labeled 15-mu microspheres were injected into the medullary canal of rat femurs. The ratio of injected particles found in the femur was compared among groups that received application of a tourniquet prior to injection, no tourniquet, or transection of all soft tissue proximal to the injection site. Obliteration of circulation in the soft tissue surrounding the femur with a tourniquet or tissue transection did not alter the spread of particles from the femur. The pulmonary circulation trapped approximately 95% of particles reaching the lungs, limiting their access to peripheral arterial circulation. If the number of particles injected into the femur was increased, the number of particles leaving the femur increased at an even greater rate. These data suggest that (1) a particle can exit the femur without traveling through the soft tissue surrounding the femur; (2) most particles that reach the lung are retained; and (3) the injected bone acts as a sponge, retaining some particles and permitting the rest to enter the venous drainage. PMID- 2924475 TI - Characteristics of successful and unsuccessful applicants to orthopedic residency training programs. AB - In 1985 there were 288 applicants for the ten postgraduate Year 1 orthopedic residency positions in Galveston and San Antonio, of which 119 (41%) applicants successfully obtained a residency position in one of 76 orthopedic programs approved by the Accreditation Council for Graduate Medical Education. Successful applicants were younger and had higher Medical College Admissions Test scores, National Board of Medical Examiners, Part I (NBME-I) scores, and medical school grade point averages than unsuccessful applicants. Variables that increased acceptance rates were medical student status, an NBME-I score above 500, class rank in the top 40%, and membership in Alpha Omega Alpha honor society. Foreign citizenship and prior residency experience in a different specialty strongly decreased acceptance rates. Variables that did not affect acceptance rates were: gender, military experience, marital status, graduate degree, research, publications, or NBME-II scores. PMID- 2924476 TI - Intraarticular sodium hyaluronate injections in the Pond-Nuki experimental model of osteoarthritis in dogs. I. Biochemical results. AB - An established anterior cruciate ligament deficiency-induced articular cartilage degeneration was used to evaluate the effects of intrasynovial injection of hyaluronic acid upon cartilage destruction. In this study, proteoglycan solubility under associative and dissociative conditions was compared in two treatment protocols at intervals of seven, 13, and 17 weeks after surgical breakage of the anterior cruciate ligament in 2.5-year-old Beagle dogs. Untreated joints showed a marked increase in both total soluble glycosaminoglycan (GAG measured as uronic acid) and in the associative fraction. In both treated groups, there was a reduced amount of soluble GAG. Cessation of treatment after seven weeks caused gradual regression, with an increasing amount of CaCl2-soluble material in the associative fraction, while inception at seven weeks gave biochemical evidence of reversal, with increasing GAG present in the guanidine soluble (dissociative) fraction on the insoluble residue. The protective effects of hyaluronic acid suggest the potential clinical application of this therapy in retarding the advance of osteoarthritis. PMID- 2924477 TI - Bone resorption. PMID- 2924478 TI - Controlled mechanical stimulation in the treatment of tibial fractures. AB - Although it is known that the mechanical environment affects the fracture healing process, the optimal conditions for the different stages of healing have not been defined. In the present studies, the influence of applying a very short period of axial micromovement with defined characteristics to healing fractures has been studied both in simulated and clinical tibial fractures. The fracture healing process is seen to be acutely sensitive to small periods of daily strain applied axially within two weeks of fracture. There are boundaries of strain magnitude and force of application of applied movement that, if exceeded, inhibit the healing process. The application of appropriate applied strain to clinical tibial fractures at a time shortly after injury, when most patients would be very inactive, appears to enhance the healing process when using external skeletal fixation. PMID- 2924479 TI - Unilateral external fixation. Methods to increase and reduce frame stiffness. AB - Unilateral configurations with stiffness characteristics similar to those of the most rigid one- and two-plane bilateral constructs are easily built. Mechanically, most effective were two-plane unilateral frames with a short bone rod distance. But single- and double-bar anterior unilateral frames had the best combination of clinical and mechanical features. To put gradual frame builddown on a rational basis, a sequence of stepwise frame reduction was developed. This sequence leads from the most rigid unilateral constructs to frames that allow almost complete force transmission across the fracture site while still providing adequate protection against the prevailing sagittal bending moments. PMID- 2924480 TI - A primer of fixator devices and configurations. AB - This paper gives a general introduction to the terminology, concepts, and classifications of external fixators. A clear distinction is made between characteristics typical of the three types of external fixators, simple, clamp, and ring, and those typical of the four standard frames that can be built with each of the devices. These four frames, the one-plane unilateral, two-plane unilateral, one-plane bilateral, and two-plane bilateral configurations, differ in the ease of wound access they allow and their mechanical balance, particularly toward bending moments. Hybrids of different devices and frames may prove beneficial for stabilizing complex injuries. PMID- 2924481 TI - Plaster cast versus external fixation for unstable intraarticular Colles' fractures. AB - This study compares 75 consecutive patients with Frykman Type VIII fractures of the distal forearm treated by primary external fixation with 32 patients who sustained similar injuries and were treated by closed reduction and cast immobilization. The latter group of patients served as an historical control. The two groups were similar with respect to injury and demographic characteristics. All fractures treated with external fixation remained well reduced and aligned, whereas 88% of those treated with casts had unsatisfactory alignment despite the fact that 30% had a second reduction. The external fixator group also had superior results with respect to functional outcome, range of motion, and grip strength. PMID- 2924482 TI - External fixation of femoral fractures. Indications and limitations. AB - The role of external fixation in the management of femoral shaft fractures is reviewed based on a study of 24 femoral fractures managed by either an AO or a Wagner external fixator during 1983-1986. Indications included open fractures with soft-tissue injury (13 patients), comminuted shaft fractures (six patients), and unstable operative candidates (five patients). In 14 patients, external fixation was a temporary method (Group I), while in ten patients it was the definitive method of stabilization (Group II). Twenty-one patients achieved solid union, two developed a delayed union, and one had a nonunion. Three patients developed pin-tract infections, and one developed osteomyelitis after intramedullary fixation in Group I. Two patients in Group II developed shortening (2.1 cm and 3.2 cm). Loss of motion occurred in 11 patients, averaging 56 degrees. It is suggested that external fixation be considered in the following types of femoral fractures: open fractures for aggressive management of soft tissue injuries; closed fractures in severely traumatized, burn, or head injury patients; fractures about the knee resulting in floating knees; and infected femoral nonunions and pseudarthroses. PMID- 2924483 TI - Plates versus external fixation in severe open tibial shaft fractures. A randomized trial. AB - A prospective study of 59 patients with Grade II or III open tibial shaft fractures compared internal and external fixation. Bony stabilization was with plating by AO principles or with external fixation with the one-half pin technique, prospectively randomized. In 12 cases, minimal internal fixation of the tibia and external fixation were combined. Definitive wound closure was delayed in all cases. Three free-flap transfers and two gastrocnemius myoplasties were done; vascular injury necessitated three early limb amputations. Fifty-six patients were followed for at least one year. Five plate fixations (19%) were complicated by severe osteomyelitis, and three plate fixations failed. Severe osteomyelitis occurred in one case (3%) treated with external fixation. Three pin tract infections occurred. In two patients, a 10 degrees anteroposterior angulation occurred after external fixation removal. One patient healed with a 25 degrees external rotation deformity. At final follow-up evaluation, all tibial shaft fractures had healed. Knee and ankle ranges of motion were affected by ipsilateral femoral shaft fracture, knee injury, or ankle and foot trauma but not by the type of fixation. Both methods yielded excellent results, but the rate and extent of complications were lower with external fixation. Therefore, external fixation using the one-half pin technique should be regarded as a primary method of stabilization for Grades II and III open tibial shaft fractures. PMID- 2924485 TI - Rigid fixation and bone grafts in craniofacial surgery. PMID- 2924484 TI - A biomechanical analysis of the Ilizarov external fixator. AB - Five configurations of the Ilizarov fixator were analyzed in vitro. The overall stiffness, shear stiffness, and axial motion of the fracture site were determined. The data were compared with the results of eight conventional one half frame fixators previously tested in the same manner. The Ilizarov fixator allowed significantly more axial motion at the fracture site during axial compression than the other fixators tested. The overall stiffness and shear rigidity of the Ilizarov external fixator were similar to those of the one-half pin fixators in bending and torsion. The stability of the Ilizarov fixator was a function of bone position within the fixator rings and fixation wire tension. The use of olive stop wires increased the shear resistance of the Ilizarov system. PMID- 2924486 TI - Panfacial fractures: organization of treatment. AB - Recent advances in facial trauma management have enabled the surgeon to perceive and successfully reconstruct complex panfacial injuries. Restoration of both preinjury facial aesthetics and function is now the goal. An organized approach to these injuries begins at the maxillary and mandibular arches with progression to the vertical mandible. The nasoorbital ethmoidal complex is stabilized to the cranium and bone grafted when indicated. The zygomatic complex is related medially, and orbital reconstruction performed. The facial architectural restoration is completed at the Lefort I level. Adherence to this protocol enables the surgeon to obtain reproducibly good results, even with the most extensive facial dislocations. PMID- 2924487 TI - Fractures of the frontal sinus. AB - It is not possible to establish rigid guidelines for the treatment of frontal sinus fractures. However, this series demonstrates that aggressive treatment of the sinus with damage to the frontal sinus drainage system will produce a "safe" sinus. The individual surgeon must base his or her treatment philosophy on the type and severity of injuries being treated, the patient population involved, and his or her experience with each of the treatment options. All patients must be made to realize that they have a life-long risk for delayed complications following any type of reconstructive procedure on the frontal sinus. It is hoped that patients who do experience complications will seek treatment when the first symptoms of a frontal sinusitis arise, rather than allowing the infection to progress to a more severe state that is life-threatening or may require disfiguring surgery. PMID- 2924488 TI - The significance of condylar position using rigid fixation in orthognathic surgery. AB - Rigid fixation in orthognathic surgery has major advantages, particularly the elimination of postoperative intermaxillary fixation, which makes the procedure more comfortable for the patient. The main disadvantage of rigid fixation in these procedures is that errors in the position of bony segments and dislocations of the mandibular condyle during surgery may result in errors of the occlusion and cause adverse effects on the temporomandibular joint. When rigid fixation is used, the presurgical position of the condyles should be maintained. The principles of condylar positioning are described. PMID- 2924489 TI - Rigid skeletal fixation in maxillary osteotomies. Intraoperative control of condylar position. AB - In isolated maxillary osteotomies the condylar positioning technique cannot be performed because the autorotation of the mandible following maxillary movements cannot be calculated in advance. The only possibility to achieve an exact position of the maxillary segment in relation to the skull base and the temporomandibular joint is the intraoperative control of the condylar position using a face bow transfer during surgery. Errors in the condyle position would result in an error of the occlusion and would cause adverse effects on the temporomandibular joint. PMID- 2924490 TI - Rigid fixation and osteotomy design in frontal orbital advancement osteotomies. AB - The advantages rendered by corrective osteotomies that mobilize large segments of the craniofacial complex, including the forehead, orbits, and maxillae, exceed those of any partial correction in this particular region. This fact has been fully demonstrated in recent years by different authors. An inconvenience of early correction of major craniofacial deformities is relapse at the maxillary level, mainly because of the lack of adequate dental occlusion. Rigid fixation methods have been used in surgical correction of Crouzon's disease and Apert's syndrome in order to preserve the position of the mobilized segments. In Crouzon's cases conventional monoblock advancements were performed, using anchor wire osteosynthesis at the frontal region and two metal plates attached to the temporal bone to support the middle third of the face. In Apert's syndrome cases, a monoblock advancement modified by the facial bipartition concept was the selected procedure to obtain a three-dimensional correction. Because a midfacial vertical elongation was necessary, a third plate joins the hemi faces, fixing them to the intermediate frontal bar. Advantages of this method have been demonstrated over the past 2 years. Sixteen children had a one-stage reconstruction by multiple osteotomies and extensive, combined mobilizations of the craniofacial complex. Successful long-lasting corrections attest to the efficacy of this fixation method. PMID- 2924491 TI - The use of the Wurtzberg system to facilitate fixation in facial osteotomies. AB - Results of the use of titanium miniplates for the management of fractures and elective osteotomies in the craniofacial region in 40 patients over the past 24 months are reported. Titanium as a biomaterial, the benefits and liabilities of rigid internal fixation, and the effects of using miniplates upon surgical practice are discussed. Clinical examples are provided to illustrate actual usage of craniomaxillofacial miniplates. PMID- 2924492 TI - Plate and screw fixation in the management of mandible fractures. AB - The use of compression plates and screws in the management of mandibular fractures is a reliable method of producing rigid internal fixation and a functionally stable fracture site. Early mandibular function is possible, resulting in a decrease in intermaxillary fixation time, improved oral hygiene and nutrition, and maintenance of normal neuromuscular physiology. Compression osteosynthesis results in primary bone healing, which has been shown to hasten osseous regeneration. With adherence to strict technical details and the use of sound clinical judgment, compression plate and screw techniques provide for a predictable method in the treatment of mandible fractures. PMID- 2924493 TI - Open reduction of mandibular condyle fractures. Indications and technique. AB - The traditional approach of closed reduction for condylar fractures has proved to be effective in an overwhelming majority of patients, but not in all. Some authors have proposed open reduction in selected cases. At present, there are no long-term data supporting open reduction to prevent future joint problems. In view of this, I believe that the best overall indication for open reduction is the surgical need to place the face or jaws in the proper functional position. PMID- 2924494 TI - Computed tomography of the chest in the trauma patient. AB - Thirty-six (1.5%) of 2340 patients admitted to the Trauma Unit at UCSD Medical Center over a 26-month period had 46 chest CT scans. A retrospective review of these cases showed that CT was useful in the diagnosis and management of suspected post-traumatic infective complications, assessment of suspected sternoclavicular joint dislocation, and localisation of bullet fragments. Other unsuspected abnormalities (pneumothoraces, misplaced endotracheal tube, intraperitoneal air, and axillary vein disruption) were also well demonstrated. However, CT failed to demonstrate some skeletal injuries, in particular, manubriosternal joint dislocation and vertebral fracture. Our experience supports a role for chest CT in certain limited clinical situations following trauma. PMID- 2924495 TI - Non-Hodgkin's lymphoma of the nasopharynx, paranasal sinus and palate. AB - Twenty-two patients with non-Hodgkin's lymphoma of the nasopharynx, paranasal sinuses or palate were treated between 1952 and 1980. The histology was reviewed by one histopathologist and 77% of cases were classified as grade 2 non-Hodgkin's lymphoma. Forty-five per cent of patients relapsed after initial treatment and 41% of all patients died from lymphoma. The 5-year survival ranged from 22% for the nasopharynx to 80% for the palate. PMID- 2924496 TI - The radiological manifestations of relapsing polychondritis. AB - Four patients with relapsing polychondritis are described. The radiological appearances of the arthropathy and the tracheobronchial involvement are illustrated, and the value of these findings in early diagnosis and management are emphasised. PMID- 2924497 TI - Difficulties in diagnosis of congenital H-type tracheo-oesophageal fistulae. AB - The case notes of 12 children with congenital H-type tracheo-oesophageal fistulae diagnosed at the Hospital for Sick Children, Great Ormond Street, who presented between 1980 and 1986 were reviewed. All patients presented early in the neonatal period with recurrent chest infections; abnormal chest radiographs were found in eight. Ten of a total of 19 contrast studies were negative. Tube oesophagograms were more likely to demonstrate a fistula than conventional contrast studies. Any delay in surgery was due to delay in diagnosis rather than to delay in presentation. The results suggest that tube oesophagograms should be performed early where there is clinical suspicion of an H-type fistula, and that other investigations (for example bronchoscopy) should be considered if the tube oesophagogram does not demonstrate a fistula. PMID- 2924498 TI - Assessment of computed tomographic artefact in the pituitary fossa following needle implantation of radioactive rods. AB - Computed tomographic scans of the pituitary fossa following treatment of pituitary tumours by interstitial irradiation were reviewed for the degree of metallic artefact created by the rods. Among 50 patients treated with 90Y rods alone, none showed artefact to a degree that caused technically unsatisfactory images in coronal or axial cuts. Among the seven patients who had been treated with 198Au, either alone (two patients) or with both 198Au and 90Y rods (five patients), six had severe artefact and in five of these the images were technically unsatisfactory in both coronal and axial slices. We conclude that following implantation of 90Y rods, the currently preferred isotope, the pituitary fossa can be satisfactorily assessed by computed tomography. PMID- 2924499 TI - Acquired coronal cleft vertebra. AB - Five patients with acquired coronal clefts in lower lumbar vertebral bodies are presented. The appearances on plain radiographs, skeletal scintigraphy, discography, computed tomography and magnetic resonance imaging (MRI) are described. The aetiological factors are discussed with particular emphasis on the role of the intervertebral disc and the discovertebral junction in the pathomechanics of vertebral body injury. Magnetic resonance imaging was helpful in the radiological assessment and provided information from which an explanation of the clefts could be proposed. PMID- 2924500 TI - Radiology is valuable to general practitioners; but who pays? AB - This study evaluated an open access general practitioner radiological service. Questionnaires were completed in 216 out of 250 cases both before and after radiological examination. Chests and specials (bariums, intravenous urography, ultrasound) were most often of diagnostic value when confirming normality, while other radiographs were more likely to be of value in assessing the severity of known disease (P less than 0.001). Patient therapy was altered in 31% of cases following receipt of the radiological report, and management was changed in 40%. In 25% of cases the patient was discharged on receipt of the report. In 28% of cases the report avoided a hospital referral. Special examinations were most likely (P less than 0.05) to avoid a referral. It is concluded that open access radiology is a considerable help with diagnosis and management, and substantially reduces out-patient referrals. The possible consequences for the acute services of providing a full general practitioner diagnostic service are discussed. PMID- 2924501 TI - The treatment of essential thrombocythaemia with radioactive phosphorus. AB - The major complications of essential thrombocythaemia include haemorrhage and thrombosis, events which are related to the level of the abnormal platelet count. We report here on the use of radioactive phosphorus (32P) in eight patients with essential thrombocythaemia. Two patients required multiple injections of 32P to control platelet count, and there was no reduction in the rate of fall of platelets with each injection. Three patients required chemotherapy for persistent thrombocythaemia despite multiple doses of 32P. No clinical or haematological characteristics could be identified for those patients whose disease was difficult to control. Radioactive phosphorus is a safe and effective method to control platelet counts in patients with essential thrombocythaemia. PMID- 2924502 TI - Reversal of vocal cord palsy by tamoxifen. AB - Advanced breast carcinoma responds to tamoxifen in more than 30% of cases (Mouridsen et al., 1978). It is widely used for hormonal treatment in women suffering from breast carcinoma, particularly if they are post-menopausal (Carter, Bakowski and Hellmann, 1981). PMID- 2924503 TI - Carcinoma of the oesophagus--a review of 108 cases treated by radical radiotherapy. AB - A retrospective survey was made of 108 patients accepted for radical radiotherapy over a 10-year period. The crude 5-year survival was 8.3% (9 of 108). Patients aged 65 years and over fared significantly better than patients aged less than 65 years (P = 0.04). Long-term survival was more likely with the following features: females, good general condition, tumour in the upper third of oesophagus and no more than 8 cm in length. The 5-year survival for upper third cases was 15.6% (7 of 45) so that for this site radiotherapy can reasonably be considered the treatment of choice. Hypothyroidism developed in three of the seven upper third long-term survivors. PMID- 2924504 TI - Hypophosphataemic rickets and melorheostosis. AB - Hypophosphataemic rickets/osteomalacia has been described in association with fibrous dysplasia and neurofibromatosis. This is the first reported case of melorheostosis associated with hypophosphataemic rickets. The literature is reviewed regarding the known association with the other bone dysplasias. PMID- 2924505 TI - Magnetic resonance imaging of an intradural spinal lipoma: a case report. AB - A case of an extensive cervicothoracic intradural lipoma in an adolescent is presented. The myelographic, computed tomography and magnetic resonance findings are described. PMID- 2924506 TI - Defining a 'unit of harm'. PMID- 2924507 TI - Luteinizing hormone in women is secreted in superimposed pulse patterns. AB - 1. The pulsatile nature of luteinizing hormone (LH) secretion has recognized physiological and clinical importance, but because of the difficulties with statistical analysis of serial data the precise nature of this pulsed signal is poorly understood. Several groups have noted small-amplitude, high-frequency pulses superimposed on large slower pulses, but, using conventional methods of analysis, it is not possible to distinguish these from assay variation or to characterize them. 2. In an alternative approach we have applied the methods of time series analysis which identify the harmonic patterns within data. Twenty four healthy women in the early follicular phase of the cycle had blood samples taken at intervals of 1, 5 or 10 min for up to 6 h. 3. We found that LH secretion consists of superimposed harmonics of varying amplitude which occur in frequency bands of about (a) 1-3 h and (b) 2-3 min. Investigations excluded a reproducible pulsatility in our LH assay, implying that the small fast pulses are physiological events. 4. We conclude that LH release is highly complex and that the methods of time series analysis permit identification and characterization of the multiple pulses. PMID- 2924508 TI - Plasma dihydroxyphenylglycol for estimation of noradrenaline neuronal re-uptake in the sympathetic nervous system in vivo. AB - 1. Neuronal re-uptake is the primary means for terminating the actions of endogenously released noradrenaline. A portion of the recaptured noradrenaline is deaminated to form dihydroxyphenylglycol. The present report describes a technique using plasma dihydroxyphenylglycol for estimation of the rate of neuronal reuptake of endogenous noradrenaline in vivo. 2. Neuronal re-uptake of noradrenaline in the sympathetic nervous system of the rat was estimated from the effects of neuronal uptake blockade with desipramine on three variables: (i) the plasma clearance of intravenously infused 3H-labelled noradrenaline, (ii) the plasma concentration of endogenous dihydroxyphenylglycol, and (iii) the plasma concentration of 3H-labelled dihydroxyphenylglycol formed from infused 3H labelled noradrenaline. 3. Desipramine decreased plasma dihydroxyphenylglycol by 36%, this representing the fraction of dihydroxyphenylglycol in plasma that was derived from recaptured noradrenaline. After desipramine, the decrease in the rate of neuronal uptake of 3H-labelled noradrenaline was 9.7 times that of the decrease in the plasma spillover of 3H-labelled dihydroxyphenylglycol. Since the appearances in plasma of dihydroxyphenylglycol from unlabelled and 3H-labelled noradrenaline were similar, the neuronal re-uptake of endogenous noradrenaline could be assumed to be 9.7 times as much as the plasma spillover of dihydroxyphenylglycol that was derived from recaptured noradrenaline (0.15 nmol min-1 kg-1). 4. The rate of neuronal re-uptake of endogenous noradrenaline was estimated to be 1.45 nmol min-1 kg-1, whereas the plasma spillover of noradrenaline was 0.127 nmol min-1 kg-1. Thus, only a small fraction (less than 9%) of the noradrenaline released into the synaptic cleft spills over into the circulation. PMID- 2924509 TI - Human whole-blood granulocyte aggregation in vitro. AB - 1. Aggregation assays are a commonly used technique for the study of granulocyte activation. These studies are usually performed using a pure cell suspension in buffer. This necessitates a separation procedure which is time-consuming and may modify the function of the cells. Interaction between different cell types is precluded. 2. To avoid these disadvantages a method was developed which quantifies granulocyte aggregation in whole blood. Samples drawn from an incubated vessel before and after the addition of a chemotactic stimulus were fixed with formaldehyde to prevent disaggregation. Erythrocytes were then removed by chemical lysis and using an electronic cell-sizing device the number of single cells and aggregates could then be easily measured. 3. Results from a group of volunteers showed a rapid and reversible response to a chemotactic tripeptide, with a fall in single granulocyte count and the appearance of doublets and triplets. Lymphocytes were unaffected. Intra-assay reproducibility was better than +/- 5%. 4. Using this assay, a significant elevation in aggregability was observed in blood from patients after acute myocardial infarction. 5. This novel technique, by avoiding the separation step, is faster, simpler and more physiological than previous methods, and as such is useful for both assays of drug action in vitro and the study of cell activation in disease states. PMID- 2924510 TI - Effects of chronic hypokalaemia and adrenalectomy on potassium transport by the medullary collecting duct of the rat. AB - 1. The purpose of this study was to evaluate the roles of chronic hypokalaemia and of aldosterone in K+ transport in the medullary collecting duct. Renal clearance and duct transport measurements were made before and after KCl infusion in three groups of animals: normal rats on a regular K+ diet (group I), and sham operated (II) or adrenalectomized rats (group III), both on a low K+ diet. 2. Only the sham-operated animals on the low K+ diet became hypokalaemic. They also had the lowest rate of K+ excretion at the time of study. Adrenalectomized rats were normokalaemic, and had an intermediate rate of K+ excretion. After the acute KCl infusion, kaliuresis remained significantly depressed in the rats which were previously hypokalaemic. In contrast, K+ excretion rates in response to K+ infusion were high and not significantly different in both previously normokalaemic groups, independent of the presence of the adrenal glands. 3. In the medullary collecting duct, before the KCl infusion there was no net K+ transport in either normokalaemic group (I and III). However, after the KCl infusion there was significant K+ secretion in both of these groups (32% and 22% of total urinary excretion, respectively). In contrast, the sham-operated hypokalaemic rats on the low K+ diet had a small absolute, but large fractional K+ reabsorption (64% of delivered load) in the medullary collecting duct. With KCl infusion in this group, K+ delivery to the medullary duct increased, but absolute reabsorption along the duct was maintained, resulting in a fractional reabsorption of 28% of delivery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2924511 TI - Plasma levels of the lyso-derivative of platelet-activating factor are related to age. AB - 1. The effect of age on the plasma level of the lyso-derivative of platelet activating factor (lyso-PAF) was studied in 72 normal subjects, (32 females, 40 males) aged 12-64 years. Lyso-PAF was acetylated in vitro to PAF which was measured by bioassay using 5-[14C]hydroxytryptamine-labelled rabbit platelets. 2. Under 40 years there were similar direct relations between plasma lyso-PAF and age in both sexes (linear regression; males, P less than 0.001; females, P less than 0.002), the level approximately doubling from the adolescent level around 100 ng/ml. However, in the later years the levels fell, the fall seeming to commence earlier in females, so that between 40 and 65 years the level was greater in males [169 +/- 47 (SD) vs 120 +/- 30 ng/ml; P less than 0.01]. 3. The increase in plasma lyso-PAF up to middle-age may be related to the reported increase in prostanoid production with age, since these platelet and vasoactive compounds can have a common origin in membrane phospholipid. This would be consistent with increasing phospholipase A2 activity and decreasing stability of cell membranes with age, but the later fall in lyso-PAF is then unexplained; the lesser values in females than males in the more advanced years could be related to females' generally lesser vascular disease. However, knowledge of the biological roles and metabolism of PAF is still very limited and the real significance of the findings remains to be determined. PMID- 2924512 TI - Relationship between leucocyte sodium content and high blood pressure during development and resolution of pre-eclampsia. AB - 1. One hundred and five primigravidae were followed sequentially at 4-weekly intervals starting at gestational week 31. They were seen again at 6 weeks post partum. 2. At each visit measurements were made of blood pressure as well as of leucocyte and erythrocyte sodium and potassium content. 3. Eighty-five subjects completed the study. Seven developed pre-eclampsia. 4. In both controls and patients who developed pre-eclampsia, leucocyte and erythrocyte sodium content increased with gestational age and fell post partum. These changes were of greater magnitude in the patients with pre-eclampsia. Cell potassium fell in both groups, but to a greater extent in patients with pre-eclampsia. 5. These changes in cell sodium paralleled those in blood pressure in both groups. 6. These data suggest that the excessive blood pressure changes in pre-eclampsia might be related to similar changes in cell sodium content. PMID- 2924513 TI - Extrarenal potassium adaptation: the role of aldosterone. AB - 1. Prior adaptation to a high potassium (HK) diet reduces the increment in plasma potassium after nephrectomy and acute potassium loading. Previous work has suggested that this 'extrarenal potassium adaptation' is due to direct stimulation of cellular potassium uptake by chronic hyperaldosteronism. 2. In contrast, we have shown that when dietary potassium is withdrawn from HK rats, large urinary potassium losses persist, resulting in 'paradoxical potassium depletion'. This potassium depletion facilitates cellular potassium uptake and is, at least in part, responsible for extrarenal potassium adaptation. 3. To try to reconcile these observations, we explored further the role of aldosterone in extrarenal potassium adaptation. When dietary potassium was withdrawn from chronically adrenalectomized HK rats, paradoxical potassium depletion was markedly blunted and extrarenal potassium adaptation could not be demonstrated. Similarly, urinary potassium losses and potassium depletion were reduced when acute adrenalectomy was performed concomitantly with dietary potassium withdrawal. 4. We were unable to confirm previous studies showing extrarenal potassium adaptation in the absence of potassium depletion. Thus, extrarenal potassium adaptation did not occur after pretreatment with chronic high-dose mineralocorticoid, after prior adaptation to a sodium-free diet, or after prior adaptation to an extremely HK diet in the absence of dietary potassium withdrawal. 5. We conclude that chronic hyperaldosteronism is important in extrarenal potassium adaptation, but probably not via direct enhancement of cellular potassium uptake. Rather, in HK animals, hyperaldosteronism magnifies urinary potassium losses during fasting and thus promotes potassium depletion, which in turn facilitates the uptake of an acute potassium load. PMID- 2924514 TI - Pindolol, not verapamil, in combination with digoxin is the treatment of choice in chronic atrial fibrillation. PMID- 2924515 TI - Effect of postural change and thermoregulatory stress on the capillary microcirculation of the human toe. AB - 1. We have applied the technique of television capillary microscopy to make direct measurements of nutritional capillary flow in the toe nailfold (i) at heart level and (ii) in a near standing position, with the foot 96 cm below heart level. By indirect heating we have examined the relationship between posture related changes and thermoregulation in the capillary circulation of the toe. 2. Capillary blood flow in 14 male subjects with their feet at heart level showed a positive correlation with increasing skin temperature. 3. On quiet standing, capillary blood flow decreased to 11.3% of supine values, achieved both by a reduction in capillary blood velocity and the duration of flow. 4. Indirect heating of the trunk led to a partial release of sympathetic tone and induced a significant increase in capillary blood flow in both the supine and dependent positions. However during heating, the percentage fall in capillary blood flow associated with dependency remained unchanged. 5. In conclusion, it appears that in the dependent foot, compensatory mechanisms exist to limit nutritional capillary blood flow by regulating both erythrocyte velocity and the duration of flow. These mechanisms fulfil a physiological requirement to limit the rate of oedema formation. The preservation of this response during the partial sympathetic release induced by indirect heating suggests a mechanism independent of that controlling flow through arteriovenous shunts. Our results are compatible with the hypothesis that a local vasoconstrictor mechanism is operative in the vascular resistance elements in closest relation with the capillary bed, and distal to that regulating arteriovenous shunt flow. PMID- 2924516 TI - Ascorbic acid: a factor concentrated in human gastric juice. AB - 1. Concentrations of ascorbic acid (ascorbic and dehydro-ascorbic; A + D; measured by the 2,4-dinitrophenylhydrazine method) of nearly three times those of plasma are present in gastric juice samples from patients with normal gastric histology. 2. A significant reduction in gastric juice ascorbic acid (A + D) was observed in patients with chronic gastritis. This reduction in concentration was independent of the grade of gastritis. 3. Concentrations of ascorbic acid (A + D) in gastric biopsy specimens were consistently higher in the antrum than in the body of the stomach. 4. These data demonstrate that considerable quantities of ascorbic acid (A + D) are normally 'secreted' into the stomach. 5. Ascorbic acid (ascorbic only; A; measured by h.p.l.c.) was present predominantly in its biologically active form in the patients with normal gastric histology. However, in patients with gastritis, independent of grade, ascorbic acid was present predominantly in its oxidized, biologically inactive form. PMID- 2924517 TI - Effect of aminophylline on plasma and urinary catecholamine levels during heavy leg exercise in healthy young men. AB - 1. Methylxanthines have been shown to elevate the basal plasma level and/or urinary excretion of noradrenaline (NA) and adrenaline (ADR) in healthy subjects. The present study addressed the hypothesis that the methylxanthine aminophylline also augments plasma and urinary catecholamines during increased sympathoadrenal activity. 2. Eleven healthy young men performed a maximal 2 h bicycle exercise twice, after double-blind intravenous administration of placebo or aminophylline. Femoral venous plasma and urinary concentrations of NA and ADR were analysed in samples representing basal state, exercise and recovery, using liquid chromatography with electrochemical detection. 3. Leg exercise induced eight- and six-fold increases in the plasma concentrations of NA and ADR, respectively, and seven- and four-fold increases in the urinary concentrations of NA and ADR, respectively, indicating that sympathoadrenal activity was considerably elevated. 4. After aminophylline (mean plasma concentration 20-35 mumol/l), the plasma concentrations of NA (P less than 0.001) and ADR (P less than 0.05) were independently higher at rest, during exercise and during recovery, in comparison to after placebo; the mean exercise plasma level of NA was increased by the drug from 13 +/- 1 to 21 +/- 2 nmol/l and the corresponding level of ADR from 2.1 +/- 0.4 to 2.9 +/- 0.5 nmol/l. Also urinary NA (P less than 0.01) and ADR (P less than 0.05) were elevated by aminophylline; the exercise concentrations of NA in the urine were 75 +/- 8 and 97 +/- 10 mumol/mol of creatinine after placebo and aminophylline, respectively, and the corresponding levels of ADR were 12 +/- 3 and 16 +/- 3 mumol/mol of creatinine, respectively. PMID- 2924518 TI - Anaemia and reduced exercise capacity in patients on chronic haemodialysis. AB - 1. In order to evaluate the influence of varying degrees of anaemia on exercise capacity and haemodynamic parameters, 13 patients on chronic intermittent haemodialysis with haemoglobin levels between 5.1 and 12.2 g/100 ml were subjected to an exhaustive exercise test. Measurements during bicycle ergometry consisted of O2 uptake at the anaerobic threshold and of maximum O2 uptake. Resting haemodynamic parameters such as cardiac index, heart rate, stroke volume index and blood pressure were assessed non-invasively in the 13 patients undergoing exercise and in an additional three patients. 2. O2 uptake at the anaerobic threshold as well as maximum peripheral O2 uptake were severely impaired and were positively correlated with haemoglobin concentration. The strongest correlation was found between the impairment of O2 uptake at maximum workload, as assessed by maximum O2 uptake/predicted maximum O2 uptake, and haemoglobin concentration. Haemodynamic alterations in the resting state consisted of a cardiac index in the upper normal range and did not correlate with the haemoglobin concentration. 3. We conclude from our study that exercise capacity in patients on chronic intermittent haemodialysis is severely impaired and that the impairment of aerobic and anaerobic capacity is significantly correlated with the severity of renal anaemia. PMID- 2924519 TI - A comparison of the visual analogue scale and modified Borg scale for the measurement of dyspnoea during exercise. AB - 1. The intensity of breathlessness during exercise was measured in ten normal subjects using a visual analogue scale (VAS) and a Borg scale to compare the use of the scales and their repeatability, both within the duration of a period of exercise and between tests. For each scale, subjects performed two exercise tests separated by a period of 2-6 weeks. Each exercise test consisted of two cycles of progressively increasing and decreasing workload. 2. All subjects felt confidently able to use both scales to quantify their feelings of breathlessness exclusively of other sensation. Equal preference was expressed for use of a particular scale. 3. With both scales there was a large intersubject variation in the relationship between dyspnoea score and minute ventilation (VE) (P less than 0.01), and in the range of the scale used. 4. There was a good correlation between the VAS and Borg scores at each level of VE (r2 = 0.71), but the VAS score was used over a wider range than the Borg score. 5. The relationship between VE and the dyspnoea score measured by the two techniques was predominantly linear. The mean r2 for VAS score/VE was 0.68 (SD 0.19) and for Borg score/VE the mean r2 was 0.75 (SD 0.13). 6. The relationships VAS score/VE and Borg score/VE were unaffected by the direction in which the workload was varied (P greater than 0.05). 7. VE, measured at each work rate, did not differ between the two cycles (P greater than 0.05) or between the 2 days (P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2924520 TI - Responsiveness of superficial hand veins to adrenergic stimuli in patients with cystic fibrosis. AB - 1. The basic biochemical defect of cystic fibrosis (CF) remains undetermined, but impaired function of the beta-adrenoceptor-mediated adenosine 3':5'-cyclic monophosphate (cyclic AMP)-dependent regulatory pathway in secretory cells is likely to be involved in the pathophysiology of the disease. 2. We have compared responsiveness to beta-adrenergic stimulation in vivo by infusing isoprenaline locally into peripheral veins of CF patients and control subjects; the dorsal hand vein technique was used to measure the vascular response to isoprenaline. 3. CF patients required significantly higher doses of isoprenaline for half-maximal dilatation of the preconstricted veins (ED50) than controls (geometric mean: 44.5 ng/min in CF patients compared with 14.8 ng/min in controls; P less than 0.05). Maximal venodilatation was 74 +/- 30% of baseline in CF patients compared with 94 +/- 50% in controls (NS between groups). 4. The clinical score of CF patients was uncorrelated with the ED50 of isoprenaline. Thus the decreased beta-adrenergic responsiveness does not seem to be related to the severity of the disease. 5. Our results indicate a defect in the cyclic-AMP-dependent pathway in vascular smooth muscle cells of CF patients. Whether this is associated with the CF gene defect itself requires further study. PMID- 2924521 TI - Hypertension and renal dysfunction in primary hyperparathyroidism: effect of parathyroidectomy. AB - 1. Twenty-four patients with primary hyperparathyroidism were studied before and 18 restudied 6.5 months (mean) after parathyroidectomy, to investigate the pathogenesis of the hypertension which may accompany this condition. Comparison was made with age-matched patients with essential hypertension and with normotensive control subjects. 2. There was a significant inverse relationship between mean arterial pressure and 51Cr-labelled ethylene-diaminetetra-acetate (51Cr-EDTA) clearance in patients with hyperparathyroidism both before and after parathyroidectomy, but not in patients with essential hypertension. 3. Creatinine clearance appeared to overestimate glomerular filtration rate in some patients with hyperparathyroidism, falling significantly after surgery while 51Cr-EDTA clearance was unchanged. This observation may explain the failure of some previous studies to relate hypertension to impairment of renal function. 4. Plasma renin activity, plasma aldosterone and whole-body exchangeable sodium did not differ between normotensive and hypertensive patients with primary hyperparathyroidism and were unchanged after surgery. 5. Parathyroidectomy did not result in any change in blood pressure or in glomerular filtration rate measured by 51Cr-EDTA clearance. PMID- 2924522 TI - Absorption and metabolism of cholesterol in familial hypercholesterolaemia. AB - 1. The present study investigated the role of intestinal cholesterol absorption in the regulation of cholesterol metabolism and serum lipoprotein levels in 22 patients with heterozygous familial hypercholesterolaemia on low to normal cholesterol intake. 2. The results showed that the higher the dietary cholesterol absorption, the lower was the overall synthesis of cholesterol. Efficient cholesterol absorption actually reduced the elimination of cholesterol as faecal neutral sterols but not consistently as bile acids. 3. In multifactorial analysis, body mass index and dietary plant sterols were negatively associated with cholesterol absorption, but were unrelated to cholesterol synthesis. 4. Fractional cholesterol absorption was related only to the serum very-low-density triacylglycerol level. It was not associated with the total or low-density lipoprotein cholesterol levels. On the other hand, cholesterol synthesis was significantly associated with the serum concentrations of very-low-density lipoprotein and intermediate-density lipoprotein cholesterol and triacylglycerols, and with those of low-density lipoprotein triacylglycerols. 5. In conclusion, dietary cholesterol absorption is an essential regulator of cholesterol homoeostasis in familial hypercholesterolaemia, even in patients on low cholesterol intake. PMID- 2924523 TI - Renal kallikrein activity in rats developing spontaneous hypertension. AB - 1. Spontaneously hypertensive rats (SHR) excrete less kallikrein in urine than Wistar-Kyoto rats (WKY) during the developmental phase of hypertension. The present study was designed to examine whether the urinary defect is related to abnormalities in the renal kallikrein content in this hypertensive model. 2. Active and total kallikrein were measured (amidolytic assay) in the renal cortex of newborn and 4-, 8- and 12-week-old SHR and age-matched WKY. Active and total kallikrein were also measured in urine at the same ages, except at birth. 3. Tissue active kallikrein was significantly lower in SHR at birth, representing on average 53% of the values in WKY expressed as content per total cortex weight. Tissue total kallikrein did not differ between newborn SHR and WKY. 4. SHR at 4, 8 and 12 weeks of age had lower urinary active and total kallikrein excretion. Tissue active akllikrein, but not total kallikrein, was higher than in age matched WKY per g of cortex weight or per mg of protein, whereas both tissue active and total kallikrein were lower in SHR when expressed as content per total cortex weight. At these three ages, active kallikrein represented, on average 86%, while total kallikrein represented 77%, of the values in age-matched WKY. 5. Our results indicate a defect in prokallikrein activation rather than in kallikrein synthesis in the renal cortex of SHR at birth. The reduction in urinary kallikrein excretion during the developmental phase of hypertension in young SHR is similar to the reduction observed in the renal tissue. PMID- 2924524 TI - Altered interactions between glycogenesis and lipid synthesis after liver resection: specific effects of liver regeneration, coupled with non-specific effects of surgery. AB - 1. This work investigated the relationship between glycogenesis and lipid synthesis during liver regeneration after partial hepatectomy in the rat. 2. Rates of lipid synthesis were increased during the first 2 post-operative days; these elevated rates were unaffected by starvation. By contrast, glycogen concentration were decreased even after 8 post-operative days, by which time liver mass had been restored and concentrations were sensitive to nutritional status. 3. The results of experiments involving the intragastric or intraperitoneal administration of glucose indicated that increased lipid synthesis was unlikely to be a consequence of decreased glycogenesis, but that depletion of liver glycogen might be linked both to liver cell division and, in the longer term, surgical stress. PMID- 2924525 TI - Different cation transport inhibitor in malignant renal hypertension and in uraemia. AB - 1. We investigated whether the previously reported circulating frusemide-like factor in rats with malignant renal hypertension was specific to this syndrome, or was also present in rats with chronic uraemia. 86Rb uptake (K+ transport) of monolayers of vascular smooth muscle cells was measured in the plasma of rats with malignant one-kidney, one-clip hypertension and of uraemic rats (60-70% nephrectomy). 2. Compared with control plasma, ouabain-insensitive 86Rb uptake of cells was reduced and ouabain-sensitive 86Rb uptake was unchanged in the plasma of rats with malignant hypertension. The reverse was found in the plasma of uraemic rats. 3. Inhibition of ouabain-sensitive 86Rb uptake of cells occurred in the plasma of rats with malignant hypertension when an angiotensin II antagonist was added to the reaction mixture. 4. The findings confirm the presence of a frusemide-like plasma factor in malignant hypertension and a ouabain-like plasma factor in uraemic. The presence of a ouabain-like plasma factor in malignant hypertension is camouflaged by an elevated circulating angiotensin II level, which stimulates K+ transport. PMID- 2924526 TI - Sodium and lithium handling in the isolated hypertensive rat kidney. AB - 1. Isolated kidneys taken from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) were perfused over a range of perfusion pressures. 2. Lithium clearance was used as an index of proximal tubule sodium handling. 3. When the perfusate contained an oncotic agent (albumin, 6.7 g/dl) the SHR kidneys performed differently from the WKY kidneys with a reduction in inulin clearance, sodium excretion, fractional sodium excretion and fractional lithium excretion [at 105 mmHg (14 kPa) perfusion pressure, SHR 6.0 +/- 1.1% vs WKY 12.6 +/- 2.4% (mean +/- SEM); at 150 mmHg (20 kPa), SHR 17.1 +/- 1.6% vs WKY 27.0 +/- 2.3%]. Calculated indices of distal tubular function showed no major differences between SHR and WKY. 4. When kidneys were perfused without oncotic agent in the perfusate the differences between SHR and WKY in tubular handling of sodium and lithium were largely abolished. 5. These findings are consistent with the hypothesis that increased sodium reabsorption occurs in the proximal tubules of the kidneys of SHR and suggest that this is an intrinsic property of the kidney, not immediately dependent on neural or humoral factors. Increased sodium reabsorption in the proximal tubule may contribute significantly to the existence of hypertension in the SHR. PMID- 2924527 TI - A preventive law plan for the Colorado AIDS Control Law. PMID- 2924528 TI - Cholesterol screening. PMID- 2924529 TI - Numerical competence in a chimpanzee (Pan troglodytes). AB - A chimpanzee (Pan troglodytes), trained to count foods and objects by using Arabic numbers, demonstrated the ability to sum arrays of 0-4 food items placed in 2 of 3 possible sites. To address representational use of numbers, we next baited sites with Arabic numbers as stimuli. In both cases performance was significantly above chance from the first sessions, which suggests that without explicit training in combining arrays, the animal was able to select the correct arithmetic sum for arrays of foods or Arabic numbers under novel test conditions. These findings demonstrate that counting strategies and the representational use of numbers lie within the cognitive domain of the chimpanzee and compare favorably with the spontaneous use of addition algorithms demonstrated in preschool children. PMID- 2924530 TI - Rhesus monkeys (Macaca mulatta), video tasks, and implications for stimulus response spatial contiguity. AB - Recent reports (Iwai, Yaginuma, & Mishkin, 1986; Yaginuma & Iwai, 1986) have supported the earlier conclusion by Meyer, Treichler, and Meyer (1965) and by Stollnitz (1965) that the efficiency of primate learning is compromised to the degree that there is spatial discontiguity between discriminanda and the locus of response. The research reported in this article calls for a reconsideration of this conclusion. Two rhesus monkeys (Macaca mulatta) easily mastered precise control of a joystick to respond to a variety of computer-generated targets despite the fact that the joystick was located 9 to 18 cm from the video screen. We hold that stimulus-response contiguity is a significant parameter of learning only to the degree that the monkey visually attends to the directional movements of its hand in order to displace discriminanda as in the Wisconsin General Test Apparatus. If, instead, attention is focused on the effects of the hand's movement rather than on the hand itself, stimulus-response contiguity is no longer a primary parameter of learning. The implications of this work for mirror guided studies are discussed. PMID- 2924531 TI - Antipredator defensive behaviors in a visible burrow system. AB - Analyzed defensive behaviors in a seminatural setting through videorecordings of groups of 4 male and 4 female rats. Before cat exposure dominant males showed more offensive behavior, eating, drinking, and use of the open area than subordinates. Presentation of a cat in the open area produced changes in four subpatterns of defense over a 24-hr period: withdrawal; immobility and movement constraint; risk assessment; and suppression of nondefensive behaviors. All Ss showed pronounced and consistent changes in each of these patterns, but dominant males alone showed increased risk assessment-related corner runs. These results provide an extensive description of rat defensive behaviors in a seminatural and relatively unstructured situation and suggest that the anxiety process is initially associated with withdrawal and movement arrest, giving way to a crucial and long-lasting risk-assessment stage that provides information leading to either further defensiveness or a return to nondefensive behaviors. This analysis suggests new models for the study of anxiety. PMID- 2924532 TI - Litter gender composition affects maternal behavior of the primiparous mouse dam (Mus musculus). AB - Thirty-nine litters of the outbred Swiss CD-1 mouse strain were reduced at birth to 6 pups, according to three conditions: MM (all males), MF (3 males and 3 females), or FF (all females). The maternal behavior of their respective dams (frequency and duration of nursing, licking, nest-building, and other activities such as eating, drinking, sniffing, grooming, and undirected locomotor activity) were scored during a single 10-min session on Days 2, 3, 5, 7, 10, 14, and 18. Dams rearing MM litters showed higher scores of maternal care on Days 2 and 18 in the case of nursing, on Days 2, 7, and 10 in the case of nest-building, and on Day 18 in the case of licking. These results confirm previous rat data, which indicated that male and female pups are exposed early in infancy to a different pattern of maternal behavior. Concomitant measurements of pup development (body weight gain and achievement of a number of physiological and neurobehavioral landmarks) indicated that these effects of litter gender composition are not mediated by gross changes in the maturational trends of the pups. PMID- 2924533 TI - Note on hand use in the manipulation of joysticks by rhesus monkeys (Macaca mulatta) and chimpanzees (Pan troglodytes). AB - In a recent article MacNeilage, Studdert-Kennedy, and Lindblom (1987) proposed that nonhuman primate handedness may be contingent on the specific task requirements with visual-spatial tasks yielding left-hand preferences and fine motor tasks producing right-hand preferences. This study reports hand preferences in the manipulation of joysticks by 2 rhesus monkeys (Macaca mulatta) and 3 chimpanzees (Pan troglodytes). Reach data were also collected on these same subjects and served as a basis for comparison with preference data for manipulation of the joystick. The data indicated that all 5 subjects demonstrated significant right-hand preferences in manipulating the joystick. In contrast, no significant hand preferences were found for the reach data. Reaction time data also indicated that the right hand could perform a perceptual-motor task better than the left hand in all 5 subjects. Overall, the data indicate that reach tasks may not be sensitive enough measures to produce reliable hand preferences, whereas tasks that assess fine motor control produce significant hand preferences. PMID- 2924534 TI - Protein kinase C from sea urchin eggs. AB - 1. Protein kinase C is considered to be ubiquitous in tissues and organs; however, its isolation and characterization have been principally with adult mammalian tissues. 2. There is increasing evidence for the importance of this enzyme during early development. 3. In this study, protein kinase C has been identified and partially characterized in cytosolic fraction from sea urchin eggs. 4. The enzyme was resolved from other protein kinase activities by ion exchange chromatography. 5. Phosphatidylserine and Ca2+ were required for protein kinase C to be active. 6. Diacylglycerol and phorbol ester enhanced the activation of the enzyme. PMID- 2924535 TI - Purification and characterization of a galactose-binding lectin from the skin mucus of the conger eel Conger myriaster. AB - 1. A galactose-binding lectin was purified from the skin mucus of the conger eel Conger myriaster by affinity chromatography and HPLC. 2. The lectin was a simple protein having the same two subunits with a mol. wt of 12,500 and a N-terminal amino acid of phenylalanine. 3. Electrofocusing suggested that the purified lectin was composed of several isolectins. 4. From the ultraviolet difference spectra attributable to tryptophanyl residues in the binding site, the binding constant of the lectin for D-galactose was estimated to be 5.3 x 10(3)/M. PMID- 2924536 TI - Distribution of fatty acid binding proteins in tissues and plasma of Gallus domesticus. AB - 1. Fatty acid binding activity associated with a 14,000-15,000 mol. wt protein was observed in the cytosolic fraction of liver, duodenum, myocardium, adipose, pectoral and gastrocnemius muscles of chickens. 2. Polyclonal antisera prepared against chicken liver fatty acid binding protein affinity for only liver FABP and a 14,000 mol. wt fatty acid binding protein in the intestine. 3. A fatty acid binding protein was not detected in chicken plasma. PMID- 2924537 TI - Porphobilinogenase from Rhodopseudomonas palustris. AB - 1. Porphobilinogenase (PBGase) from Rp. palustris has been isolated and some properties of a partially purified fraction were studied. 2. PBGase has an optimum pH of 7.4 when activity was expressed in terms of porphyrins formed and two pH maxima at 7.4 and 8.5 when activity was based on the amount of PBG consumed. 3. Cyclotetramerization rate and distribution of reaction products were not affected either by the presence or absence of oxygen. 4. Two PBGase active species of mol. wt 115,000 and 50,000 were found, by means of gel filtration through a calibrated Sephadex G-100 column. 5. Kinetic data show the existence of positive cooperative effects for porphyrin formation, while a hyperbolic behaviour for PBG consumption was observed. PMID- 2924538 TI - Blood glucose partition and levels of glycolytic enzymes in erythrocytes and somatic tissues of penguins. AB - 1. A comparative study was carried out on blood glucose partition and glucose metabolism of penguin erythrocytes and somatic tissues. Pygoscelidae penguins (Pygoscelis antarctica and P. papua) were used in these experiments. 2. Blood glucose partition was established by assaying whole blood and plasma glucose in several individuals of the gentoo and chinstrap penguins. 3. It was found that almost all the whole blood sugar is compartmentalized at the plasma site, the red blood cells being ineffective in regard to glucose metabolism. 4. Levels of hexokinase, phosphoglucose isomerase, phosphofructokinase, fructose bisphosphate aldolase, glyceraldehyde phosphate dehydrogenase, phosphoglycerate kinase, phosphopyruvate hydratase (enolase), pyruvate kinase, alpha-glycerolphosphate dehydrogenase and fructose bisphosphate phosphatase were estimated in the erythrocytes of both gentoo and chinstrap penguins, the same determinations being carried out also on the somatic tissues (leg muscle, breast muscle, heart muscle, liver and brain) of the gentoo. PMID- 2924539 TI - Fatty chain composition of phospholipids in sea urchin spermatozoa. AB - 1. An analysis was made of lipids extracted from the spermatozoa of the sea urchins, Hemicentrotus pulcherrimus and Anthocidaris crassispina. 2. Nearly all the lipids from both species consisted of phospholipids (about 80%) and cholesterol (about 14%). Triglyceride and cholesterol ester were present in trace amounts. 3. The fatty acid composition of each phospholipid was determined by gas liquid chromatography. In both species, the fatty acid consisting of phosphatidylethanolamine was of the unsaturated type for the most part, while cardiolipin was comprised to a considerable degree of saturated fatty acids. In phosphatidylcholine and phosphatidylserine from H. pulcherrimus sperm, unsaturated fatty acid content was somewhat higher than that in phospholipids from A. crassispina sperm. PMID- 2924540 TI - Semicarbazide-sensitive amine oxidase activity in catfish tissues. AB - 1. Semicarbazide-sensitive amine oxidase activity was found in five tissues of the siluroid catfish, Parasilurus asotus, using benzylamine as substrate. It was highest in the intestine, followed by the liver and skin. 2. The apparent Km value and optimal pH for benzylamine in the intestine were 49.8 microns and 8.8, respectively. 3. Substrate specificity of the enzyme was tested in the intestine and the highest activity was found with beta-phenylethylamine, followed by tryptamine and benzylamine. PMID- 2924541 TI - A simple method for measuring immunoglobulin synthesis in vivo in the spleen of chicks (Gallus domesticus). AB - 1. Spleen immunoglobulin (IgG) synthesis was measured in vivo in chicks at 3 weeks of age by a large dose injection of labelled phenylalanine in combination with the isolation of IgG by immunological precipitation against anti-chicken IgG. 2. No appreciable amount of radioactivity was detected in serum IgG for the first 60 min of the isotope injection via the wing vein, indicating a minimum time lag necessary for the secretion of newly synthesized IgG into the circulation. 3. Synthesis rates of total spleen protein and spleen IgG were found to be 17.5 and 4.8 mg/day, respectively, suggesting that IgG synthesis would contribute to 27% of the total protein synthesis in the spleen of young chicks. PMID- 2924542 TI - Classical bile acids in animals, beta-phocaecholic acid in ducks. AB - 1. Bile samples of different animals were analysed and the percentage content of classical bile acids was determined. 2. Herbivorous birds mostly excreted a large proportion of chenodeoxycholic acid. 3. The anteater (Myrmecophaga tridactyla) excreted deoxycholic acid most probably as a primary bile acid. 4. In the bile of ducks (Anas platyrhynchos) a large amount of (23R)3 alpha, 7 alpha, 23-trihydroxy 5 beta-cholan-24-oic acid (beta-phocaecholic acid) was found. PMID- 2924543 TI - Electrophoretic transferrin variation in fur seals (Arctocephalus spp.) at Marion Island. AB - 1. Variation in transferrin types were investigated in sympatric populations of two fur seal species which are undergoing limited hybridization at Marion Island. 2. Vertical polyacrylamide gel electrophoresis of serum was performed to demonstrate the transferrin types. 3. The two species appear fixed for alternative alleles: A. tropicalis being homozygous for the fast allele, and A. gazella (with one exception) being homozygous for the slow allele, indicating low gene flow between these two species. The single hybrid tested was homozygous for the slow allele. 4. The use of electrophoretically determined transferrin variation holds promise for the investigation of these and other sympatric fur seal populations. PMID- 2924544 TI - Adenylate energy charge and hemoglobin function in developing mouse embryos. AB - 1. Adenylate energy charge (EC) was measured in mouse embryos and showed a significant rise from 0.79 at day 11 of gestation to 0.87 at day 15 (P less than 0.05). 2. The low value of EC between days 11 and 13 corresponds with the predominance of the embryonic hemoglobin fraction E-I which has high affinity and poor cooperativity. 3. The highest value of EC corresponds with the predominance of adult hemoglobin which has lower affinity and cooperative oxygen binding. 4. Weight-specific oxygen uptake rates of isolated embryos decreases with weight gain and it is suggested that the energy charge is a manifestation of metabolic regulatory processes which sustain embryonic growth. PMID- 2924545 TI - Molecular forms of acetylcholinesterase from the skeletal muscle of the ammocoete of the lamprey Petromyzon marinus. AB - 1. We have studied the cholinesterase activity from the skeletal muscle of the ammocoete of the lamprey Petromyzon marinus. 2. On the basis of pharmacologic and kinetic criteria, we conclude that the enzyme is true acetylcholinesterase, not pseudocholinesterase. 3. The acetylcholinesterase was found to be present in both globular and asymmetric forms. 4. In contrast to muscle of adult spawning lamprey, where globular esterase is almost exclusively G4, we found that muscle from ammocoete also contains significant amounts of G1 and G2. 5. This difference may be related to the physiological states of the lamprey during the various stages of its life cycle. PMID- 2924546 TI - The isozymes of lactate dehydrogenase, malate dehydrogenase and glucosephosphate isomerase in Italian ictalurids. AB - 1. The isozymes of lactate dehydrogenase (LDH), malate dehydrogenase (MDH) and glucose-phosphate isomerase (GPI) of three species of Italian ictalurids: Ictalurus sp., I. nebulosus marmoratus, and I. punctatus, were analyzed. 2. Isoelectric focusing (IEF) was applied to polyacrylamide gel plates, and the isozymes revealed by means of specific histochemical staining. 3. Species specific monomorphic patterns were found for LDH. 4. In contrast, MDH and GPI have the same patterns in I. sp. and I. nebulosus marmoratus and different patterns in I. punctatus. 5. Comparison of the isozymatic patterns of the three species clearly showed the close relationship between I. sp. and I. nebulosus marmoratus and the relative taxonomic distance of I. punctatus, and thus the early detachment of this last species from a presumptive common ancestral lineage. PMID- 2924547 TI - Enzymatic properties of fish muscle aldolase. AB - 1. Aldolases were isolated from the ordinary muscle of red sea bream Pagrus major, Pacific mackerel Scomber japonicus, and carp Cyprinus carpio by ammonium sulfate fractionation, followed by ion-exchange chromatography on DEAE-cellulose and CM-Sepharose CL-6B columns, and examined for enzymatic properties. 2. The aldolases showed the highest activity in a pH range from 6.8-7.8 Km values for fructose-1,6-bisphosphate ranged from 0.025-0.10 mM. 3. Irrespective of fish species, aldolase activity was inhibited by ATP, ADP, and AMP. ATP showed the strongest inhibition and was competitive with fructose-1,6-bisphosphate. 4. The aldolases did not require divalent metal ions for activation and were completely inhibited at 0.1 mM Cu2+. 5. Thermal inactivation of the enzymes was of the first order reaction. Red sea bream, Pacific mackerel and carp enzymes lost the activity by 50% when incubated at 50 degrees C for 8, 14 and 23 min, respectively. PMID- 2924548 TI - Computer-controlled large-animal pulmonary function system. AB - Breath by breath determination of lung volume and specific lung conductance is challenging, yet desirable particularly when rapid changes in lung function accompany abrupt changes in lung volume. We have developed a large-animal pulmonary function data acquisition system using two personal computers with custom-made software which continuously tracks breath by breath changes in pulmonary function and lung volume. Accurate measurement of respiratory flow signals is accomplished by collecting separate pneumotachometer-derived expiratory and inspiratory flow signals, correcting them to standard temperature pressure dry (STPD) and summing them into a single flow data array. Calibration of inspiratory and expiratory flow is software corrected by comparison of the integrated flow signals with a sinusoidal pump system. Data are collected continuously for up to 120 min at 100 Hz/channel. Subroutines which configure the system to perform functional residual capacity, dosimetry and partial expiratory flow-volume maneuvers are user selected at any time during data collection. PMID- 2924549 TI - A real-time system for the spectral analysis of the EEG. AB - We have developed an inexpensive and portable system for processing multiple channels of electroencephalograms (EEG) in real-time to assist the electroencephalographer in identifying subtle changes in these data, particularly in the interpretation of long records. Up to 16 channels of data are spectrally decomposed with a selection of bandwidth, windows, scaling methods, epoch averaging, and smoothing options available. The resulting power spectral estimate may be displayed or printed in a variety of formats, including color encoding of selectable spectral bands. Both the sampled EEG and its spectra may be stored for off-line reprocessing, for archiving, or for statistical analysis in the time or frequency domains. PMID- 2924550 TI - Computer-assisted predictive mathematical relationship among electroshock voltage and duration and occurrence of convulsion in mice. AB - A microcomputer program in BASIC for predicting percentage of occurrence of electroshock-induced convulsion in mice was designed. A formula published by the author to express the mathematical relationship among the drug dose, the time, and the biological response was used in this program. Analysis of the actual, and the computer-assisted predicted percentages of occurrence of convulsion has shown that the program is fairly accurate in expressing convulsion response of mice as a function of the voltage and the duration. PMID- 2924551 TI - Development of personal computer software for a visual electrophysiology laboratory. AB - This paper describes the software developed by the authors in order to introduce the flexibility and computing power of a modern personal computer in an existing visual electrophysiology laboratory. The basic problems that a programmer must solve in order to implement the main tasks requested are discussed. Such problems include signal acquisition, signal averaging, artifact rejection, time domain analysis, frequency domain analysis and data management. The software developed following our guidelines makes it possible for a personal computer equipped with a commercial analog-to-digital converter to interface directly with the physiologic amplifiers and visual stimulators commonly used either for classical electroretinography or for pattern and focal electroretinography. PMID- 2924552 TI - A computer program for summarizing scatter plots with robust ellipses. AB - This paper describes a program for summarizing scatter plots with robust ellipses. The program is written in BASIC and is designed for interactive use on a microcomputer graphics terminal to enable quick redesigns of the graph. PMID- 2924553 TI - Data processing software for electrophysiological visual exploration. AB - The software we have developed originated after careful study of a routine functional visual processing session. It has three objectives: (i) to have available a large library of data processing programs; (ii) to add to these electrophysiological results, automatically transferred into a file, a clinical record card, creating a personalized file for study of visual characteristics of each patient; (iii) to allow programs providing statistical studies, creation of groups based on the same clinical features and various comparisons between files or groups. The database now contains 5000 different files and the results of its use are very encouraging. Some results are presented, especially those of a study on multiple sclerosis. The goal of the operation is the creation, in the future, of an expert system. PMID- 2924554 TI - PC-based system for classifying dysmorphic syndromes in children. AB - A system is described running on any IBM-compatible personal computer operating under MS-DOS which permits an expert in pediatric dysmorphology to formulate dysmorphic features and syndromes in a knowledge base, and a user to enter, analyze, store and retrieve case data. For each case, the system calculates the Bayesian probability of the presence of each syndrome in the knowledge base and lists as the differential diagnosis those syndrome whose probability exceeds 90%. For explanatory purposes, the syndrome definitions can be displayed and compared to the case data. The system has been tested and used in the Department of Clinical Genetics at Uppsala University Hospital. The current scope of the system's knowledge was found to be of valuable assistance to the pediatric practitioner but it must be expanded and refined for use by a clinical geneticist. This study has shown the validity of the system's design and structure and further work is under way to extend its knowledge capability. PMID- 2924555 TI - A microcomputer program to calculate elemental analysis of peptides. AB - A BASIC program is presented that calculates the elemental analysis of peptides given their primary sequence. This program is aimed to help synthetic chemists in the characterization of their products. The program runs on any IBM-compatible computer with the MS-DOS operating system, version 2.0 or greater, and the results are printable on any connected printer. PMID- 2924556 TI - A computer program for drawing structure formulas of the hormonal steroids used most frequently in endocrinology. AB - A BASIC program has been developed for plotting planar structure formulas of steroid hormones. The structure formulas can be designed either by selecting distinct root-molecule shapes for further figuration of the wanted formula, i.e. androstane, 4-androstene, estrogen, cholestane, pregnane or 4-pregnene structures, or by editing detailed information concerning the molecule to be designed, starting with the number of carbon atoms, etc. The position of hydroxy and/or keto groups, as well as some stereochemical details, are also freely selectable according to the systematic steroid name. Graphs are displayed on the screen and can be printed. The program is supported by most of the conventional BASIC versions running on personal computers with graphic abilities, since graphic symbols are predominantly used for drawing the structure formulas instead of lettering the symbols. PMID- 2924557 TI - A BASIC program for randomizing and balancing the order of interventions in crossover studies. PMID- 2924558 TI - Thermodynamic network modelling of transfer across the perfused guinea-pig placenta, using SPICE. AB - The response of the dually perfused guinea pig placenta to bolus inputs of the marker substances 125I-albumin and tritiated water is used to model vascular placental topology and membrane characteristics. This is accomplished by generating a thermodynamic network containing ten adjustable variables describing flow and transfer quantitatively. After translation of the network into an electronic circuit the parameter values are determined with the use of the SPICE program. The results are then used to estimate unknown physiological variables like shunted flow, membrane permeabilities, etc. This model has potential usefulness in the study of those areas of placental physiology in which transient analysis is required. PMID- 2924559 TI - BIOLAB--a computerized on-line system for physiological measurements in experimental animals. AB - An on-line system for the acquisition and analysis of physiological signals measured in experimental animals is described. The modular design makes it flexible and easily adaptable to various kinds of physiological measurements. Currently, the system includes support for hemodynamic and cardiac electrophysiological studies. The system is designed for intermittent recordings initiated either manually by the operator or automatically. The distributed computer system consists of three parts: the data acquisition subsystem, the on line analysis subsystem, and the final data processing subsystem. The communication between the subsystem utilizes an Ethernet local area network, and the analysis and plot programs include support for RS/1 tables and graphs. PMID- 2924560 TI - Hash function performance on different biological databases. AB - Open hashing is used to demonstrate the effectiveness of several hashing functions for the uniform distribution of biological records. The three types of database tested include (1) genetic nomenclature, mutation sites and strain names, (2) surnames extracted from literature files and (3) a set of 1000 numeric ASCII strings. Several hash functions (hashpjw, hashcrc and hashquad) showed considerable versatility on all data sets examined while two hash functions, hashsum and hashsmc, performed poorly, on the same databases. PMID- 2924561 TI - Assessing the evolution of the evoked potential average: a new color display method. AB - A new method to control the averaging process and to check the stability of evoked potential (EP) components is described. The principle of the method is based on the display of the consecutive averages of the EP after each stimulus in a color-coded picture. In this way the evolution of the process is visualised instead of only the last average. The colors are assigned according to the amplitudes. The resulting picture initially consists of erratic colors. However, with increasing numbers of stimuli, tracks of one color soon emerge, indicating stable components. The number of stimuli necessary to generate a stable peak and the duration of stability can easily be quantified. Details with regard to the methods of extraction of essential data and data compression to record the picture are described. The color display method was evaluated with the analysis of 18 somatosensory evoked potentials and 17 visual evoked potentials of controls and 33 EPs of 18 patients. It is shown that this method preserves essential information about the averaging process: the stability of the EP components can be quantified and consequently the optimum number of stimuli to be applied. Furthermore, 14 of the 33 patient recordings showed artifacts, which could be traced with the average-evolution method, but not from the final average alone. PMID- 2924562 TI - Sexual life events and schizophrenia. PMID- 2924563 TI - Change in subtype presentation in schizophrenics. PMID- 2924564 TI - Childhood experiences of borderline patients. AB - The childhood histories of 50 outpatients meeting both Diagnostic Interview for Borderlines (DIB) and DSM-III criteria for Borderline Personality Disorder, 29 outpatients meeting DSM-III criteria for Antisocial Personality Disorder, and 26 outpatients meeting DSM-III for Dysthymic Disorder as well as DSM-III criteria for some other type of Axis II disorder were assessed, blind to proband diagnosis, using a semistructured interview. Borderlines were significantly more likely than those in either control group to report a history of abuse, particularly verbal and sexual abuse. They were also significantly more likely than antisocial controls to report a history of neglect, particularly emotional withdrawal, and significantly more likely than dysthymic other personality disorder controls to report a history of early separation experiences. The authors conclude that the development of Borderline Personality Disorder is more strongly associated with (1) exposure to chronically disturbed caretakers than prolonged separations from these same adults and (2) a history of abuse than a history of neglect. PMID- 2924565 TI - Mummification and folie a deux. AB - Mummification is the preservation of the effects and/or corpse of a loved one. Psychiatric literature regarding this condition is reviewed and a case is presented in which a mother's paranoid psychosis is discovered following her apparent mummification of her son's corpse. In retrospect, it appears that a diagnosis of folie a deux pertained to this pair. The authors contend that mummification may represent the outcome of a shared delusional system and that failure to establish psychiatric diagnoses in those who practice mummification has been the result of inherent difficulties in diagnosing paranoid disorders. PMID- 2924566 TI - Derealization and panic attacks: a clinical evaluation on 150 patients with panic disorder/agoraphobia. AB - One hundred fifty patients with Panic Disorder (PD) with or without Phobic Avoidance were subdivided into two groups on the basis of presence/absence of derealization and/or depersonalization (D-D) during panic attacks. D-D was found in 34.7% of the sample. By comparing the two groups, the patients with D-D were found to be younger and had an earlier onset of the disorder; they had a higher prevalence of avoidance behavior and a higher severity of the agoraphobic spectrum phobias. They were also more frequently subject to concomitant disorders such as Generalized Anxiety, Obsessive-Compulsive, and depressive symptomatology. The authors have hypothesized a correlation between the presence of D-D during panic attacks and a more frequent clinical evolution toward agoraphobia. This view is supported by finding that D-D in panic attacks corresponds to severer forms of PD, both in terms of the earlier onset of PD, and because PD shows higher levels of anxiety, depression, and disability. PMID- 2924567 TI - Selective attention and auditory event-related potentials in somatization disorder. AB - Janet suggested a disorder of attention was fundamental to hysteria. This idea was investigated in this study by examining mismatch negativity (MMN), which depends upon a subtraction of cortical potentials evoked by background stimuli from those evoked by target stimuli. Ten patients with somatization disorder (SMD) were compared with ten normal individuals. MMN was smaller in somatizers, particularly at the central recording site. One interpretation of this observation is that somatizers respond more similarly than normals to "relevant" and "irrelevant" stimuli. This finding of an impairment in attentional processing in somatization disorder suggests a subtle neurophysiological disturbance. PMID- 2924568 TI - Untangling the web. PMID- 2924569 TI - Preventing heartache. PMID- 2924570 TI - Mending a broken heart. PMID- 2924571 TI - Treating leg ulcers. PMID- 2924573 TI - Infant feeding: the food of love. PMID- 2924572 TI - One day at a time. Interview by Joanna Trevelyan. PMID- 2924574 TI - Prescriptive authority: an update. PMID- 2924575 TI - Communication concerns: reality or excuse? PMID- 2924576 TI - Retained placenta and mastitis. PMID- 2924577 TI - Ganglioneuroma as a cause of small intestinal obstruction in the horse: a case report. AB - The clinical signs, medical and surgical management, and pathological findings are described for a ganglioneuroma, an atypical intestinal tumor, that caused colic because of small intestinal obturation. PMID- 2924578 TI - Erysipelothrix rhusiopathiae bacteremia in a horse. AB - Erysipelothrix rhusiopathiae serotype 5 was isolated from blood obtained antemortem from a horse with presenting problems of laminitis, uveitis, acute blindness, localized ventral edema and depression. The patient failed to respond to therapy and died 96 hours after the onset of clinical signs. Cultures of the lung postmortem yielded Erysipelothrix rhusiopathiae serotype 5, Beta-hemolytic Streptococcus sp., Escherichia coli, Proteus sp., and Klebsiella sp. PMID- 2924579 TI - Treatment of patent urachus associated with a congenital imperforate urethra in a calf. AB - Patent urachus is a common condition in calves which is frequently associated with omphalitis. A membranous urethral diaphragm prevented closure of the urachus in a female calf. The patent urachus was complicated by an ascending infection of the intraabdominal umbilical remnants. Following surgical removal of the urachus and umbilical vessels along with transection of the membranous diaphragm the calf experienced an uncomplicated recovery. This case stresses the importance of assuring urethral patency when managing a case of patent urachus. PMID- 2924580 TI - Effect of experimental synovitis on disposition of penicillin and oxytetracycline in neonatal calves. AB - The effect of experimental synovitis on the distribution of antibacterial drugs into the joint space was studied in 7-day-old calves. Intrasynovial sodium urate was used to induce inflammation in the tibio-tarsal joint of calves and oxytetracycline (OTC) (11 mg/kg) or sodium penicillin G (PEN) (13.2 mg/kg) was administered intravenously 3 hours after synovitis was induced. Oxytetracycline and PEN concentrations were measured in serum and synovial fluid and pharmacokinetic parameters were calculated. The data indicate that synovitis neither enhanced nor impaired the levels of antibiotics achieved in the joint fluid. Mean peak concentrations (micrograms/ml) of the drugs in control and inflamed joints were, respectively, 8.04 and 8.79 for OTC and 9.35 and 8.92 for PEN. Rates of elimination of OTC and PEN were similar in joint fluid and serum; t1/2 beta ranged from 11.83-19.81 h for OTC and 0.980-1.125 h for PEN. The distribution and elimination of OTC and PEN from serum was described by a two compartment model whereas elimination from joint fluid was described using a single-exponential model. PMID- 2924581 TI - Idiopathic benign lichenoid keratosis on the pinna of the ear in four dogs. AB - Histologically, multiple wart-like papules or hyperkeratotic plaques on the ear pinnae from 4 dogs were characterized as idiopathic benign lichenoid keratosis. Common histologic features included a discrete lesion of irregular and papillated epidermal hyperplasia with a moderate diffuse lichenoid interface inflammatory infiltrate consisting of lymphocytes and plasma cells. There was also focal hydropic degeneration of the epidermal basal cell layer, pigmentary incontinence, and mixed orthokeratotic and parakeratotic hyperkeratosis. In all 4 dogs, the pinnal lesions were unilateral and asymptomatic. Complete surgical excision was curative. PMID- 2924582 TI - Occipitoatlantoaxial malformation with duplication of the atlas and axis in a half Arabian foal. AB - An unusual occipitoatlantoaxial malformation is described in a 2-week-old male part Arabian foal that was unable to stand at birth and showed signs of spastic tetraparesis due to a cervical spinal cord compression. There were 2 atlases present. One was fused to the occipital bones. The other articulated with the first atlas and an axis which had a long dens that projected into the vertebral canal. Examination of the ossification centers of the axis indicated partial duplication of that bone. PMID- 2924583 TI - Effects of hypertonic solutions on conjunctival epithelium and mucinlike glycoprotein discharge. AB - A simple, semiquantitative, histochemical method using periodic acid-Schiff (PAS) staining was developed to measure the mucinlike glycoprotein content of bathing solutions exposed to rabbit conjunctiva. Rabbit eyes were bathed in vivo in solutions of various tonicity (160, 260, 300, 330, and 363 mOsm/L). Eyes bathed in hypotonic or isotonic solutions (160, 260, and 300 mOsm/L) exhibited a steady state glycoprotein secretion (50-100 micrograms/h). In hypertonic solutions (330 and 363 mOsm/L), glycoprotein discharge increased to 150-360 micrograms/h when the solutions were exchanged hourly for 6 h, but glycoprotein discharge increased to a much lower rate (100-167 micrograms/h) after prolonged bathing for 6 h without solution exchange. Periodic acid-Schiff--positive glycoprotein aggregates were noted more frequently on the filters of hypertonic solutions than on those of other tonicity. After eyes were bathed in hypertonic solutions, increased disruption of the surface epithelium, increased abnormal discharge of mucin granules, and decreased goblet cell density were noted in the biopsied conjunctiva. These data suggest that mucinlike glycoprotein secretion from the conjunctival goblet cells can be enhanced by the tonicity of the bathing solution, and that nonphysiological hypertonic solutions can also affect the conjunctival epithelium. PMID- 2924584 TI - Specular microscopic studies of the corneal endothelia of Japanese diabetics. AB - We did a specular microscopic study with computer-assisted morphometric analysis of individual cells on the corneal endothelia of 69 Japanese diabetics and 53 age matched nondiabetics. No statistically significant differences were seen in the mean cell areas of diabetics and nondiabetics. However, the coefficient of variation of cell area was significantly higher and the percentage of hexagonal cells was significantly lower in diabetics than in nondiabetics. Although racial differences of the corneal endothelia exist between Japanese and Americans, diabetic changes are quite similar in the two populations. PMID- 2924585 TI - Automated determination of polygonality of corneal endothelial cells. AB - We developed a computer program for the image analyzer NEXUS 6400. The program enables automated determination of polygonality, especially hexagonality of corneal endothelial cells, by counting the number of neighboring cells. The results obtained with the method significantly correlated with those determined with the digitizer method. PMID- 2924586 TI - Lack of toxicity of a topical recombinant interferon alpha. AB - We evaluated the potential ocular surface toxicity of a recombinant interferon alpha (IFN alpha) preparation on rabbit eyes. Topical application of this interferon (1 x 10(6) U/day in each eye) for 6 weeks produced no discernible conjunctival or corneal abnormalities on clinical, histopathologic, or ultrastructural evaluations. We believe that this recombinant IFN alpha preparation is not toxic to the ocular surface of rabbits. PMID- 2924588 TI - Society of Critical Care Medicine, eighteenth annual educational and scientific symposium. New Orleans, Louisiana, June 5-9, 1989. Abstracts. PMID- 2924587 TI - Ligneous conjunctivitis after pingueculae removal in an adult. AB - A 45-year-old man who had uneventful excision of bilateral pingueculae developed bilateral membranous lesions involving the bulbar conjunctivae and corneas. Histologically, the membranes were composed mainly of large fibrinous deposits intermixed with acute and chronic inflammatory cells with areas of fibroblastic and capillary proliferation resembling granulation tissue. By electronmicroscopy the amorphous acidophilic masses were composed of electron-dense, fibrillar material with a periodicity of 10-12 mm, which was consistent with fibrin. Despite mechanical removal of the membranes, they continued to recur rapidly over a period of several months. The lesions apparently responded slowly to topical enzymatic therapy that consisted of hyaluronidase (175 U/ml) and alpha chymotrypsin (1:5000) drops. Follow-up examination, approximately 1 year after surgery, revealed that the patient was asymptomatic. Ocular examination disclosed slight persistence of gelatinous membranes on the bulbar conjunctivae, most prominent in the left eye. PMID- 2924589 TI - Diagnosis and management of complications of percutaneous nephrolithotomy. AB - The therapeutic management of the complications of percutaneous nephrolithotomy (PNL) depends on the early recognition of these complications. A review of 720 cases revealed the incidence of significant complications to be less than 4%. An algorithm was developed as a guideline for the diagnosis and management of complications of PNL. Early complications included transient bleeding (83 cases), extravasation of urine (52 cases), significant infection (11 cases [2 with septicemia and shock]), and migration of stone fragments into the retroperitoneum (7 cases). Nonrenal complications were present in less than 6% of these patients. These included pleural effusions or pneumothorax (24 cases) and lung atelectasis (19 cases). Late complications were seen in less than 2% of the patients. These included stricture of the ureter with obstruction (5 cases), A-V fistula with or without pseudoaneurysm (7 cases), and subcapsular hematoma (1 case). Therapeutic management included improvement of technique to the use of antibiotics to treat infection. The use of proper drainage and the placement of stent or catheter in the treatment and prevention of further complications has become an integral part of the algorithm for the treatment of complications of PNL. This algorithm recommends the proper diagnostic modality for the detection and evaluation of the extent of the complication. Once detected, the complications of PNL can be minimized with limited permanent changes. PMID- 2924590 TI - Roles of unfrozen fraction, salt concentration, and changes in cell volume in the survival of frozen human erythrocytes. AB - The cause of slow freezing injury and the basis of the protection by solutes like glycerol are subjects of debate. During slow freezing, cells are sequestered in unfrozen channels between ice crystals that grow by removing pure water from the channels. As a consequence, the solute concentration in the channels rises and the volume of liquid in the channels progressively decreases. The rise in solute concentration, in turn, causes the cells to progressively shrink osmotically. Until recently cryobiologists have ascribed slow freezing injury to either the rise in solute (electrolyte) concentrations in the channels or to the consequent cell shrinkage, rather than to the decrease in the of the channels. Although ordinarily reciprocally coupled, it is possible to separate the composition of the channels from their size, or more precisely from the magnitude of the unfrozen fraction, by suspending cells in NaCl/cryoprotectant solutions in which the mole ratio of the two is held constant, but the molality of the NaCl is allowed to vary below and above isotonic. When human red cells are frozen in such solutions to temperatures that produce given NaCl concentrations (ms), but varying unfrozen fractions (U), survival at low U is found to be strongly dependent on U but independent of ms. At higher values of U, survival becomes inversely dependent on both ms and U. Although cell volume during freezing is independent of the NaCl tonicity in the solution, the cells in the several solutions differ in volume both prior to the onset of freezing and after the completion of thawing. We have now examined and compared the effect of returning the thawed cells to isotonic solutions and isotonic volume or nearly so, and find that there is little change in survival after exposure to low U, but that survival after exposure to high U values exhibits substantially increased sensitivity to ms, a sensitivity that is probably a manifestation of posthypertonic hemolysis. Low values of U were in general attained by the use of solutions with low tonicities of NaCl, and as a consequence cells frozen to low U values had larger volumes prior to freezing than cells frozen to higher U values. The significance of this confounding is discussed. PMID- 2924591 TI - The "unfrozen fraction" hypothesis of freezing injury to human erythrocytes: a critical examination of the evidence. AB - This paper examines the experimental evidence presented by Mazur and his colleagues to support their hypothesis that the survival of slowly frozen human red blood cells is primarily dependent on the fraction of water that remains unfrozen, rather than on the high concentrations of sodium chloride produced by the formation of ice. This hypothesis is in direct conflict with the general belief that freezing injury under such conditions is caused by the concentration of solutes in the solution surrounding the cells: if the "unfrozen fraction" hypothesis is true, then much of the evidence supporting that belief must be dismissed as mere coincidence. We have reexamined Mazur's data, and have suggested an alternative explanation--that cells which are initially suspended in solutions that are not isotonic differ in their susceptibility to subsequent freezing and thawing, shrunken cells being more resistant and swollen cells more susceptible than normal cells. If this is true then the data can be explained without invoking a direct effect of the unfrozen fraction, solely on the basis of changes in the concentration of the solution surrounding the cells. We cite other experimental evidence, obtained in the absence of freezing, that red blood cells do indeed possess the required property. We further argue that the known effects of variations in cooling and warming rate, and in hematocrit, are able to account for the features observed by Mazur and his colleagues in their three published studies. PMID- 2924592 TI - Quantitative analysis of the probability of intracellular ice formation during freezing of isolated protoplasts. AB - (i) A quantitative prediction of the temperature and cooling-rate dependence of IIF requires information on the probability distribution for IIF temperature; the super-cooling tolerance; and membrane permeability, initial cell size, Boyle van't Hoff relation, and other parameters associated with the thermodynamic description of cell volumetric behavior. (ii) A probabilistic analysis of IIF was developed on the basis that IIF occurs if the underlying potential IIF temperature T* falls within the range of temperatures over which the cell is supercooled beyond its tolerance delta T*. The "location" of the transition range of cooling rates, in which the Pr(IIF) increases from 0 to 1, depends on the mean of T* and delta T*. The breadth of the transition range increases strongly with variability in T*. (iii) Cryomicroscopic studies of IIF in rye protoplasts isolated from cold acclimated and nonacclimated leaves showed that the range of IIF temperatures and the incidence of IIF are strongly dependent on the solute used to manipulate osmolality in the suspending medium. The ionic solutes used in this study (NaCl + CaCl2, KCl + CaCl2, KNO3 + CaCl2) generally yielded median IIF temperatures lower than those of the nonionic solutes (sucrose, sorbitol, proline). Cold acclimation reduced the median IIF temperature for all suspending media and reduced the incidence of IIF for KCl + CaCl2, sorbitol, and proline. A Weibull distribution was found to describe adequately the distribution of IIF temperatures at the highest cooling rate. (iv) Estimates of the supercooling tolerance were generally from 1.0 to 1.5 degrees C based on the location of the transition range of cooling rates and on the estimates of Lp and delta E from (6). The breadth of the transition range of cooling rates could mostly be attributed to random variability in the underlying potential IIF temperature. The rise in median IIF temperature with higher cooling rates was correctly predicted by the model when the supercooling tolerance was also assumed to be random. For rye protoplasts, both the model and the data showed that cooling-rate dependence in median IIF temperatures occurs within the transition range of cooling rates. PMID- 2924593 TI - The effect of glycerol-related osmotic changes on post-thaw motility and acrosomal integrity of ram spermatozoa. AB - Ram semen, collected by artificial vagina, was diluted and processed for long term storage as described by P. S. Fiser, L. Ainsworth, and R. W. Fairfull (Canad. J. Anim. Sci. 62, 425-428, 1982). The concentration of the cryoprotectant, glycerol, was adjusted to 4% in the diluted semen prior to freezing by a one-step addition at 30 degrees C (Method 1), by cooling the semen to 5 degrees C and addition of the glycerol gradually over 30 min (Method 2), by one-step addition of glycerol prior to equilibration for 2 hr (Method 3), or by cooling to 5 degrees C, followed by a holding period of 2 hr at 5 degrees C, and the one-step addition of glycerol just prior to freezing (Method 4). After thawing, the glycerol concentration of the semen was reduced by stepwise dilution from 4 to 0.4% over 15 or 30 min or by a one-step ten-fold dilution. The average post-thaw percentage of motile spermatozoa was significantly lower after addition of glycerol by Method 1 (39.9%) than when the glycerol was added by the other three methods (range, 44.0-46.4% averaged over the glycerol dilution). The average post-thaw percentage of intact acrosomes (61.2%), highest in semen in which the glycerol was added by Method 2, was not significantly different from those in which glycerol was added to semen by Methods 3 and 4, but it was significantly higher than that found in semen in which the glycerol was added by Method 1 (54.4%). However, when averaged over the method of glycerolation, the post-thaw percentage of motile spermatozoa (range, 43.7-44.2%) and the percentage of intact acrosomes (range, 56.8-59.5%) did not differ significantly in semen subjected to gradual decrease in glycerol concentration and diluent osmolality (over 15 and 30 min) or by a one-step, 10-fold dilution. These data indicate that post-thaw survival of spermatozoa can be influenced by the way in which glycerol is added prior to freezing. However, post-thaw spermatozoa motility and acrosomal integrity can be maintained even after a rapid decrease in glycerol concentration such as that which accompanies insemination or dilution of semen for assessment of motility. PMID- 2924594 TI - Changes in the phospholipid composition and phospholipid asymmetry of ram sperm plasma membranes after cryopreservation. AB - The changes in the phospholipid composition of spermatozoa plasma membranes after freezing were determined by thin-layer chromatography. The results showed an augmentation of the diphosphatidylglycerol and a diminution of phosphatidylglycerol, phosphatidylserine, and phosphatidylethanolamine in sperm plasma membranes after freezing. In intact sperm cells we observed an elevation of the sphingomyelin and phosphatidylinositol levels and a diminution of the phosphatidylethanolamine and diphosphatidylglycerol levels. The effect of freezing on the phospholipid distribution between the inner and outer monolayers of the plasma membrane was also studied using exogenous phospholipases and trinitrobenzene sulfonate. The most important change we observed after freezing, was the translocation of diphosphatidylglycerol from the inner to the outer monolayer of the plasma membrane. PMID- 2924595 TI - Lipid phase transitions measured in intact cells with Fourier transform infrared spectroscopy. AB - Lipid phase transitions in membranes are thought to be a major damaging event during cooling of cells prior to cryopreservation or during warming after freeze thaw has been completed. Although there is abundant evidence that such transitions occur in isolated phospholipids, the evidence that they are found in membranes in intact cells is less clear, due largely to technical difficulties in detecting such transitions in the complex mixtures of lipids and proteins found in natural membranes. We show here that Fourier transform infrared spectroscopy provides a rapid, convenient method for detecting these transitions in intact cells. We have used intact pollen grains of cattail (Typha latifolia) as a primary experimental subject. Spectra taken of the intact pollen grains show most of the features commonly seen in natural membrane vesicles or pure phospholipids. Shifts in the vibrational frequency and width of the CH2 bands with temperature can be used to detect lipid phase transitions. Biochemical analysis, coupled with the spectroscopy, was used to assign transitions to nonpolar and polar lipids. Finally, although assignment of the melting lipid unambiguously in other cells has not yet been made, we show that the transitions can nevertheless be detected in other intact cells, including those of four plant species and sperm of three animals. PMID- 2924596 TI - An evaluation of the ability of the peripheral vasodilator buflomedil to improve vascular patency after acute frostbite. AB - The extent of microvascular damage from frostbite can be accurately demonstrated by vascular microcorrosion casting techniques (P. S. Daum, W. D. Bowers, Jr., J. Tejada, and M. P. Hamlet, Cryobiology 24, 65-73, 1987). In the present investigation, the peripheral vasodilator buflomedil was evaluated for its ability to ameliorate microcirculatory damage from acute experimentally induced freeze injury. This drug has been reported to decrease tissue loss in human frostbite patients when given intravenously during thawing (J. Foray, P. E. Baisse, J. P. Mont, and Cl. Cahen, Sem. Hop. Paris 56, 490-497, 1980). In seven groups of anesthetized rats, left hindpaws were cooled to heat of fusion; cooling continued until the temperature in the footpads fell to -15 degrees C. Prior to cooling, group 1 received a tail vein injection of 1 ml saline/kg, while group 2 received 10 mg buflomedil/kg. Immediately following cooling, group 3 received an injection of 10 mg buflomedil/kg. Hindpaws were rapidly rewarmed in a 40 degree C bath. During rewarming, left hindpaws from group 4 were immersed in deionized water, from group 5 in 24 mg buflomedil in deionized water, from group 6 in 30% dimethyl sulfoxide (Me2SO), and from group 7 in 24 mg buflomedil in 30% Me2SO. Right hindpaws served as controls. Vascular microcorrosion casts were made from left and right hindpaws of all groups. There was no significant difference in mean cast weights when frozen hindpaws of the seven groups were compared, although treatment with buflomedil increased the mean cast weight of control hindpaws from groups 3 and 7. It therefore appears that, in this acute model for frostbite, buflomedil does not improve vascular patency. PMID- 2924598 TI - Is the anatomic, diagnostic work-up of chronic cough not all that it is hacked up to be? PMID- 2924597 TI - Cytology of oocytes in ground squirrels (Citellus citellus L.). AB - Oocytes of primordial, primary, growing, and Graaf follicles of the ovaries of 96 ground squirrels (Citellus citellus L.) were studied during the four seasons of the year. Multilamellar bodies in the oocytes were observed by electron microscopy. The bodies underwent changes during the follicle growth. The vesicles included in the multilamellar bodies were filled with an amorphous substance, while in Graaf follicles trapezoidal, rhomboidal, and hexagonal inclusions were found. The primordial follicle of the oocyte had no Balbiani body. In the hibernating ground squirrel the functions of the Balbiani body were probably performed by the multilamellar bodies, which were considered to be analogous to the Balbiani body. PMID- 2924599 TI - Ambulatory monitoring of arterial oxygen saturation. AB - We have developed a method of recording oxygen saturation over time using ambulatory equipment. A pulse oximeter was modified to be powered by battery, and values for oxygen saturation were recorded by an analog recorder. The unit is compact and functions for 30 hours between battery changes. The mean difference between oxygen saturation reported by the pulse oximeter and an IL 282 CO oximeter was -1.12 percent, with a range of difference +/- 2.75 percent, indicating 95 percent confidence limits 5.5 percent either side of the mean. Continuous ambulatory recordings were obtained in 16 male subjects; six were healthy nonsnorers, five were healthy snorers, and five had sleep apnea. Of the average recording time, 19 +/- 5 hours, records contained 89 +/- 7 percent usable data. We conclude that ambulatory pulse oximetry is a feasible means of unsupervised long-term monitoring of oxygenation during daily activities. PMID- 2924600 TI - Chronic persistent cough. Experience in diagnosis and outcome using an anatomic diagnostic protocol. AB - Irwin and co-workers have designed an anatomic approach to the diagnosis and treatment of cough. In their hands, diagnosis was consistently determined and treatment successful almost without exception, if sustained. We reviewed the results of a similar approach in 139 consecutive and unselected patients referred to pulmonary specialists in two community hospitals. Thirty-nine patients demonstrated hyperreactive airways (HA) by carbachol inhalation and/or eucapnic hyperventilation of cold air. Twenty-seven of 78 without HA had postnasal drip, and 13 of 78 had a persistent cough following acute upper airway inflammation. Other less common diagnoses included chronic bronchitis, gastro-esophageal reflux, occupational bronchitis, interstitial lung disease, and psychologic causes. We were able to find the cause of cough 88 percent of the time. Treatment adjusted for noncompliance was not always a success. While all patients with HA improved, 8 percent of patients without HA or specific diagnosis did not have an improvement in their cough upon retrospective inquiry. Based on this analysis, we find that the diagnosis and treatment of cough may not be as successful as originally reported using Irwin's approach. PMID- 2924601 TI - Critical dose of digoxin for treating supraventricular tachycardias after heart surgery. AB - This study was conducted to ascertain if critical peak body stores of digoxin were needed to protect patients from the debilities that result from supraventricular tachycardias occurring after open heart operations. We gave digoxin peak body stores of 15 micrograms/kg of lean body weight to 100 consecutive patients after open heart operations. If supraventricular tachycardias persisted four hours, we increased peak body stores to 17 or 19 micrograms/kg. The operations included coronary artery bypass grafts, heart valve replacements, and congenital defect correction. After operation, 18 patients had atrial fibrillation or flutter. During supraventricular tachycardias, ventricular rates were 150 beats per minute or slower. In the 100 patients, the median hospital stay after operation was four days. No patient required rehospitalization. The patients who had supraventricular tachycardias stayed in the hospital no longer than the patients who were at all times in regular sinus rhythm. All patients who entered the hospital with regular sinus rhythm went home with regular sinus rhythm. The critical safe peak body stores of digoxin needed to prevent debilities resulting from supraventricular tachycardias after open heart operations were 15 to 19 micrograms/kg of lean body weight. PMID- 2924602 TI - Heart rate response to breath-hold, valsalva and Mueller maneuvers in obstructive sleep apnea. AB - We wished to assess the role of increased vagal tone and arterial oxygen saturation (SaO2) as determinants of HR response to voluntary respiratory maneuvers in OSAS. The changes in HR and SaO2 during breath-hold (B), Valsalva (V) and Mueller (M) maneuvers were determined in nine male subjects with OSAS while breathing RA or O2. Oxygen saturation was significantly lower breathing RA than O2 at the end of B (92.6 +/- 1.6 vs 97.2 +/- 0.8 percent), V (92.9 +/- 1.3 vs 95.2 +/- 1.7 percent), and M (92.7 +/- 1.2 vs 95.3 +/- 1.9 percent). Despite this, there was no significant difference between the HR change while breathing RA and O2 during B (12 +/- 18 vs 7 +/- 15 beats/minute), V (-2 +/- 12 vs -5 +/- 17 beats/minute), and M (5 +/- 16 vs 1 +/- 8 beats/minute). The change in HR was not related to the duration of B, V, or M or to the mouth pressure generated during V and M. In order to determine if awake HR response to the maneuvers reflected HR response to obstructive apnea, we examined the relationship between the HR response to B, V, and M during wakefulness and the response to obstructive apnea of similar duration while asleep. A significant correlation was found between the HR response to obstructive sleep apnea during sleep and the response to awake B (r = 0.67, p less than 0.001), V (r = 0.51, p less than 0.05), and M (r = 0.75, p less than 0.001). We conclude that in OSAS, increased vagal tone is a major determinant of HR response to voluntary respiratory maneuvers, that bradycardia can occur in the absence of hypoxemia, and that HR response to these maneuvers, especially to M, during wakefulness predicts HR response to obstructive apnea while asleep. PMID- 2924603 TI - Arm exercise testing with myocardial scintigraphy in asymptomatic patients with peripheral vascular disease. AB - Arm exercise with myocardial scintigraphy and oxygen consumption determinations was performed by 33 men with peripheral vascular disease, 40 to 74 years of age (group 2). None had evidence of coronary disease. Nineteen age-matched male control subjects (group 1) were also tested to determine the normal endurance and oxygen consumption during arm exercise in their age group and to compare the results with those obtained during a standard treadmill performance. The maximal heart rate, systolic blood pressure, pressure rate product, and oxygen consumption were all significantly lower for arm than for leg exercise. However, there was good correlation between all these parameters for both types of exertion. The maximal heart rate, work load and oxygen consumption were greater for group 1 subjects than in patients with peripheral vascular disease despite similar activity status. None of the group 1 subjects had abnormal arm exercise ECGs, while six members of group 2 had ST segment changes. Thallium-201 scintigraphy performed in the latter group demonstrated perfusion defects in 25 patients. After nine to 29 months of follow-up, three patients who had abnormal tests developed angina and one of them required coronary bypass surgery. Arm exercise with myocardial scintigraphy may be an effective method of detecting occult ischemia in patients with peripheral vascular disease. Those with good exercise tolerance and no electrocardiographic changes or 201T1 defects are probably at lower risk for the development of cardiac complications, while those who develop abnormalities at low exercise levels may be candidates for invasive studies. PMID- 2924604 TI - Relationship between improvement in exercise performance with supplemental oxygen and hypoxic ventilatory drive in patients with chronic airflow obstruction. AB - The purpose of this study was to determine if there is a relationship between improvement in exercise capacity with supplemental oxygen and the magnitude of hypoxic ventilatory drive in patients with CAO. We hypothesized that those patients with the highest hypoxic drives would be the most likely to have increased exercise tolerance with supplemental oxygen. Seventeen patients with CAO (mean FEV1 = 0.99 +/- 0.45 L) underwent identical maximal cycle ergometry exercise tests on two occasions 45 minutes apart while breathing either air or 30 percent oxygen in a randomized single-blind fashion. With supplemental oxygen, the ventilation decreased and the PaCO2 increased significantly at rest. The patients had a significantly greater exercise tolerance on supplemental oxygen (76.7 vs 69.1 watts, p less than 0.005) but no increase in the maximal ventilation. When the nine patients who improved were compared to the eight patients who did not improve, the two groups were basically identical. Specifically, there were no significant differences in the mean ventilatory or mouth occlusion responses to hypoxia or in the blood gases. The patients who did improve tended to have a greater reduction in their ventilatory response to exercise while exercising on oxygen as compared to when they were exercising on room air. From this study, it was concluded that measurements of hypoxic ventilatory drive are not helpful in predicting which patients with CAO are likely to have improved exercise capability while breathing supplemental oxygen. PMID- 2924605 TI - Pulmonary vascular hemodynamics in chronic lung disease patients with and without oxyhemoglobin desaturation during sleep. AB - Nonapneic, nocturnal oxyhemoglobin desaturation (NOD) during rapid-eye-movement (REM) sleep has been proposed as a predecessor and possible etiologic factor in the development of pulmonary hypertension in patients both with restrictive and obstructive chronic lung disease. The association between abnormal waking cardiopulmonary hemodynamics and NOD has not been established in patients with mild daytime hypoxemia. Gas exchange, pulmonary function, red cell mass, radionuclide gated cardiac ejection fraction, and supine cardiopulmonary hemodynamics were examined in 36 patients with chronic lung disease. All had a daytime PaO2 greater than 60 mm Hg and REM sleep-related NOD for greater than 5 minutes, to 85 percent or lower. These data were compared to those from 13 subjects with similar symptoms and objective measures of pulmonary dysfunction but without evidence of NOD. Patients with NOD showed more end organ evidence of hypoxemia and more abnormal cardiopulmonary hemodynamics than patients with similar degrees of lung disease but without NOD. The relative role of daytime vs nocturnal hypoxemia in inducing hemodynamic differences between groups cannot be determined from this study. PMID- 2924606 TI - The effects of nitrazepam and flunitrazepam on oxygen desaturation during sleep in patients with stable hypoxemic nonhypercapnic COPD. AB - Serious respiratory depression has been described in COPD patients receiving hypnotics during acute exacerbations. There are few studies quantifying the effects of hypnotics on oxygenation during sleep in patients with stable hypoxemic COPD. In this study, the effects of single therapeutic doses of nitrazepam and flunitrazepam on SaO2, apneas during sleep and other sleep variables were measured in 14 COPD patients. All patients used theophylline. Sleep-induced decrease in mean SaO2 was 1.3 percent after placebo, 1.4 percent after nitrazepam and 1.9 percent after flunitrazepam (no significant differences). Sleep apneas were not more common or longer after nitrazepam or flunitrazepam, but sleep quality seemed to improve. It is concluded that oxygenation during sleep in these nonobese patients with stable hypoxemic nonhypercapnic COPD, all on maintenance theophylline therapy, was affected very little by single therapeutic doses of nitrazepam or flunitrazepam. PMID- 2924607 TI - Cardiac function at rest and with exercise in the chronic fatigue syndrome. AB - To evaluate a possible cardiac pathophysiology of the chronic fatigue syndrome, we compared the resting cardiac function and exercise performance of 41 patients to those of an age-matched and sex-matched normal control group. Persistent fatigue following an acute apparently viral illness was the major complaint of all patients; none had specific cardiac symptoms nor abnormal physical findings. Electrocardiographic spatial patterns were normal in the patients, and there were no differences in the body surface sum of positive T-wave integrals between the patients (240 microV.x 10(2) +/- 107 microV.s x10(2)) and control (244 microV.x 10(2) +/- 108 microV.s x 10(2) subjects. Twenty-four hour ambulatory ECGs revealed no differences in sinus rates and incidences of ventricular dysrhythmias in the two populations. Left ventricular dimensions and systolic fractional shortening values were also similar in both groups; moreover none of the patients had segmental wall motion abnormalities. On graded exercise testing, 20 of 32 normal subjects achieved target (85 percent of age-maximum) heart rates, compared to four of 31 patients (p less than 0.001). The duration of exercise averaged 12 +/- 4 minutes for the normal subjects and 9+/- 4 minutes for the patients (p less than 0.01). The temporal profile of exercise heart rates was dissimilar in the two groups, with patients' rates consistently and progressively less than those of normal subjects. Peak heart rate averaged 152 +/- 16 beats per minute for the normal group vs 124 +/- 19 beats per minute for the patients (p less than 0.0001); in age-related terms, respectively, 82 +/- 6 percent of the maximum heart rate vs 66 +/- 10 percent (p less than 0.0001). Thus, patients with chronic fatigue syndrome have normal resting cardiac function but a markedly abbreviated exercise capacity characterized by slow acceleration of heart rate and fatigue of exercising muscles long before peak heart rate is achieved.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2924608 TI - Clinical experience with fulguration and antiarrhythmic therapy for the treatment of ventricular tachycardia. Long-term follow-up of 43 patients. AB - Forty-three patients (mean age, 45 +/- 18 years) with drug-refractory VT of varied etiologies, including 15 cases occurring after chronic myocardial infarction, underwent fulguration procedures. With a mean follow-up of 29 +/- 12 months (range, 9 to 55 months), after one to four sessions, VT had been controlled without a need for antiarrhythmic drugs in 22 (56 percent) of the 39 patients surviving the perioperative period and was controlled in 17 patients (44 percent) with the help of drugs. No malignant arrhythmias were observed following fulguration. There were five early deaths, four deaths related to the procedure, and eight late deaths, but no death was thought to be related to the endocardial shock itself. Thus, fulguration appears to be a valuable adjunct to the treatment of drug-resistant VT. PMID- 2924609 TI - Treatment of congestive heart failure. Its effect on pleural fluid chemistry. AB - The proper classification of pleural effusions into transudates and exudates has great clinical significance. It is believed that the treatment of congestive heart failure may convert an associated transudative pleural effusion into a "pseudoexudate." We studied eight patients with congestive heart failure during nine episodes of decompensation with pleural effusion, which was bilateral in five and right-sided in three. Thoracocentesis was done on identification of the patient and at 6 +/- 2 days after treatment of heart failure resulting in diuresis and a mean weight loss of 5.8 +/- 3.2 kg. The mean protein level of the pleural fluid was 2.2 +/- 0.7 g/dL at the initial study and increased to 3.2 +/- 1.08 g/dL at the final study (p less than 0.01). The LDH level of the pleural fluid increased from 116 +/- 69 to 183 +/- 117 units/L (p less than 0.01). The fluid/serum ratio for protein increased from 0.34 +/- 0.09 to 0.47 +/- 0.13 (p less than 0.01) and for LDH from 0.39 +/- 0.16 to 0.64 +/- 0.28 (p less than 0.01). In three patients, pleural fluid was classified as a transudate at the initial study but met the criteria for an exudate after treatment of heart failure. Effectiveness of diuresis was measured by weight loss; a significant correlation between weight loss per day and change in the protein level of the pleural fluid was noted (r = 0.715; p less than 0.05). We conclude that the treatment of congestive heart failure causes significant changes in the pleural fluid's chemistry; in some cases, a transudate may be converted into a "pseudoexudate." PMID- 2924610 TI - Homogeneity of bronchopulmonary distribution of 99mTc aerosol in normal subjects and in cystic fibrosis patients. AB - We characterized the bronchopulmonary distribution of a 0.9 percent saline aerosol (1.12 microM) labelled with 99mTc sulfur colloid in nine normal subjects and five patients with CF. Homogeneity of distribution was quantified using indices derived from computerized analysis of Anger camera pulmonary images including skew (a measure of distribution asymmetry) and kurtosis (a measure of distribution range). Aerosol clearance in 97 minutes (a measure of large, central airway deposition) was also assessed. Values of skew and kurtosis were reproducible for the patients with CF and were significantly elevated compared to the normal subjects. Reproducibility of skew and kurtosis were not studied in the normal subjects. Clearance was not significantly different in the two groups. We conclude that the bronchopulmonary distribution of this radioaerosol is nonuniform in patients with CF, compared to normal subjects, and clearance may be impaired in patients with CF who are severely ill. PMID- 2924611 TI - Pulmonary disease associated with pleural "asbestos" plaques. AB - The diagnosis of asbestos-related pulmonary disease is frequently based in part on the identification of pleural plaques; however, postmortem observations have suggested that pleural plaques may occur without associated pulmonary disease. To examine this issue, we compared the pulmonary parenchymal pathology in 93 patients with pleural plaques to 93 control patients matched for age, race, and sex, all autopsied at The Johns Hopkins Hospital between Jan 1, 1981 and March 31, 1986. Pulmonary sections were graded without knowledge of the patient's group for peribronchiolar fibrosis, other types of fibrosis, emphysema, and pleural changes. Correlations were found between the presence of pleural plaques and peribronchiolar fibrosis (p less than 0.001), alveolar fibrosis (p less than 0.05), large scars (p less than 0.02), scar-related emphysema (p less than 0.02), and pleural thickening (p less than 0.005). A history of smoking was also associated with pleural plaques (p less than 0.05). Interstitial fibrosis was not significantly different between the two groups. Peribronchiolar fibrosis was neither universally nor exclusively present in patients with pleural plaques, being found in 49 (53 percent) of 93 subjects with and 36 (39 percent) of 93 subjects without plaques. The results suggest that caution must be exercised in extrapolating from the identification of pleural plaques to a diagnosis of asbestos-related pulmonary disease. PMID- 2924612 TI - Rounded atelectasis. Clinical experience with 74 patients. AB - Rounded atelectasis is an atelectasis of a peripheral part of the lung due to pleural adhesions and fibrosis causing deformation of the lung and bending of some small bronchi. From 1970 to 1986, some 74 patients with rounded atelectasis have been seen at the Lung Department. Sixty-four of these patients had been exposed to asbestos. The lesion was secondary to a benign asbestos pleurisy in nine patients and resulted from a slowly increasing pleural fibrosis in 13 patients; in the remaining 39 patients with exposure to asbestos, rounded atelectasis was a sudden finding, with earlier roentgenograms showing only plaques or being normal. Three patients had bilateral lesions, and one had no fewer than three small rounded atelectases. All of the asbestos-exposed patients were men. Ten patients (four women and six men) had not been exposed to asbestos. Two of these cases occurred after trauma and four after a pleural exudate. One of the latter was the only one which disappeared spontaneously. The lingula was affected in 33 cases, the middle lobe in 16, the right lower lobe in 12, the left lower lobe in 11, the right upper lobe in six, and the left upper lobe (except the lingula) in one. Nine patients underwent surgery. Operation should be avoided; the typical roentgenologic and CT findings combined with negative results of bronchoscopy (and, in some cases, fine-needle biopsy) will suffice to exclude malignancy. PMID- 2924613 TI - Carborundum pneumoconiosis. Fibers in the mineral activate macrophages to produce fibroblast growth factors and sustain the chronic inflammatory disease. AB - Carborundum is a synthetic abrasive manufactured through fusion of high grade silica sand and finely ground carbon in an electric furnace at 2,400 degrees C. It had been considered an inert dust until recently. Two recent epidemiologic studies in Quebec have documented an excess of interstitial lung disease in plant workers and some 30 workers have received workman compensation. Histopathologic lesions have been described in four of the workers. To further investigate the carborundum pneumoconiosis, nine groups of eight sheep were exposed once in the tracheal lobe to either 100 ml saline, 100 mg latex beads in 100 ml saline, 100 mg graphite in 100 ml saline, 100 mg carborundum particles in 100 ml saline, 100 mg ashed carborundum particles in 100 ml saline, 100 mg of quartz (Minusil-5) in 100 ml saline, 100 mg crocidolite fibers in 100 ml saline, 100 mg carborundum fibers in 100 ml saline, and 100 mg ashed carborundum fibers in 100 ml saline solutions. The animals had BAL at two-month intervals and autopsy at month 8. The BAL analyses of cellularity, cytotoxicity and fibrogenicity, in association to necropsy histopathology, documented that all particles except for quartz were inert. The two-carborundum fiber samples produced a similar sustained nodular fibrosing alveolitis and crocidolite asbestos fibers produced a peribronchiolar fibrosing alveolitis of comparable severity. Thus, the major bioactive dusts in the carborundum manufacturing process are quartz particles and the carborundum fibers generated in the process. The latter have fibrogenic activities comparable to asbestos fibers of similar size and are likely to contribute to the pathogenesis of the interstitial lung disease of carborundum workers. PMID- 2924614 TI - Preoperative and postoperative abnormalities in chest x-ray indices and in lung function in pectus deformities. AB - In 88 patients with pectus deformities radiologic chest indices and routine pulmonary function tests were measured before and 1 to 20 years after corrective surgery. A combination of anteroposterior indices at the upper and lower level of the chest were investigated to quantitate and to discriminate the different pectus deformities. The study comprised four groups: pectus excavatum, pectus carinatum, pectus deformatum and pectus excavatum with scoliosis. These indices were also assessed in 250 healthy males and females. Generally, several indices showed significant and discriminative changes in the different patient groups and improved again after surgery. Preoperative lung function was decreased in pectus excavatum only. In all groups lung function worsened after surgery. A stepwise discriminant analysis performed on the large group with pectus excavatum indicated that postoperative lung function was decreased if the preoperative value of FEV1 or VC was more than about 75 percent predicted and vice versa, but that it was not related to other factors such as radiologic indices, age at operation or time since operation. PMID- 2924615 TI - A new pendant oxygen-conserving cannula which allows pursed lips breathing. AB - Multiple benefits of oxygen therapy for hypoxemic patients with chronic lung disease are well established. Steady flow oxygen therapy is inefficient, wasteful and has a high cost. The Oxymizer pendant improves efficiency of oxygen delivery compared with SF. However, the device requires that the patient inhale and exhale nasally to maximize its oxygen-saving properties. When patients do PLB they may not receive full oxygen-saving benefit of the pendant. Yet PLB itself can increase SaO2. We evaluated an AP, which does not require nasal exhalation, in nine patients with COPD. We measured SaO2 while breathing oxygen via SF and the AP with nasal-only breathing and PLB. Results indicate that the AP maintains an increase in SaO2 over SF during nasal-only breathing and a further increase during PLB. We conclude that AP acts as an oxygen conserver during PLB; PLB with the AP achieves greater savings than with nasal-only breathing. PMID- 2924616 TI - Noninvasive face mask ventilation in patients with acute respiratory failure. AB - Noninvasive face mask ventilation has been used successfully in patients with paralytic respiratory failure. This study evaluated whether noninvasive face mask ventilation can be used for patients with acute respiratory failure due to intrinsic lung disease. Six patients with hypercapnia and four with hypoxemic acute respiratory failure met clinical and objective criteria for mechanical ventilation, which was delivered with pressure control and pressure support via a tightly strapped, clear face mask. No patient terminated the study because of inability to deliver adequate ventilation or to improve oxygen exchange; three eventually required endotracheal intubation. The mask was generally well tolerated. All patients had a nasogastric tube placed on suction, and none vomited or aspirated. The mean duration of treatment was 33 h (range, 3 to 88). The physiologic response was considered similar to that which would have been achieved with conventionally delivered ventilation. Noninvasive face mask ventilation may have a role in managing respiratory failure. PMID- 2924617 TI - Hepatic dysfunction in the adult respiratory distress syndrome. AB - Multiple organ system failure is a major cause of mortality in the adult respiratory distress syndrome (ARDS). We serially evaluated parameters of multiple organ function in 24 patients during the first week after the diagnosis of ARDS and related them to outcome. The adult respiratory distress syndrome was associated with sepsis (n = 16), postoperation (n = 7), and trauma (n = 1). Fourteen of the 24 patients (58 percent) died. Although there were no significant differences in the indices of pulmonary or renal dysfunction between survivors and nonsurvivors, evidence of hepatic dysfunction was different in the two groups. On the day we identified ARDS, serum bilirubin was 1.2 mg/dl +/- 0.9 mg/dl in patients who survived, and was 2.3 mg/dl +/- 2.8 mg/dl (chi +/- SD) in those who died. Initial serum glutamic oxalacetic transaminase (SGOT) and alkaline phosphatase levels were lower in survivors than in those who died (71 +/ 44 IU/L vs 399 +/- 807 IU/L, and 121 +/- 53 IU/L vs 269 +/- 243 IU/L, respectively). These abnormalities persisted during the first week of respiratory failure, with significant differences in serum bilirubin and alkaline phosphatase between survivors and nonsurvivors (p less than 0.01). The degree of pulmonary and renal dysfunction was similar in both groups. These data suggest that liver function may be a major determinant of survival in patients with the adult respiratory distress syndrome. PMID- 2924618 TI - Selective left endobronchial suctioning in the intubated patient. AB - Suctioning of secretions from the left endobronchial tree is frequently necessary but often difficult in intubated patients. We examined the effectiveness of a catheter designed expressly for this purpose. Special curved tip (Bronchitrac-L) suction catheters were fitted with thin, radiopaque tubing to facilitate x-ray visualization. Eight-one attempts at left endobronchial placement were made on 74 stable adult intensive care unit patients. The suction catheter was inserted into the oral endotracheal tube or tracheostomy tube just prior to an x-ray filming of the chest. In 15 of 66 patients, the tip of the oral endotracheal tube was too distal (less than 2 cm above the carina) to allow proper functioning of the catheter. Patients with a properly positioned oral endotracheal tube were analyzed separately and showed 56 percent of the catheters went to the left bronchus. When the head was turned to the left prior to placement, successful left bronchus placement occurred in 65 percent. When the catheter was placed through a tracheostomy tube, 100 percent went into the left bronchus (n = 15). There were no catheter-induced complications in this study. The curved tip catheter is an effective means of suctioning the left bronchial tree in patients with tracheostomy tubes. Its reliability in patients with oral endotracheal tubes is reduced but more effective than current methods. PMID- 2924619 TI - New exercise parameter for the identification of severe coronary artery disease. PMID- 2924620 TI - Roentgenogram of the month. Exertional dyspnea and a widened mediastinum. PMID- 2924621 TI - Cutaneous signs of cardiopulmonary disease. An earlobe lesion with a lung nodule. PMID- 2924622 TI - Transient pulmonary perfusion scintigraphic abnormalities in pulmonary air embolism. AB - A critically ill man suffered a respiratory arrest due to pulmonary air embolism after the exchange of central venous catheters over a guidewire. A pulmonary perfusion lung scan performed 90 min later demonstrated extensive perfusion defects which were interpreted as "high probability" for PTE. Pulmonary angiography 4.5 h later was normal. A second perfusion lung scan performed 24 h after the respiratory arrest was normal. Pulmonary air embolism can produce segmental (and larger) perfusion defects which may be indistinguishable from those caused by PTE. The rapid (24 h) resolution of the perfusion defects may help differentiate the two disorders. PMID- 2924623 TI - Intra-atrial smoke-like echoes and thrombi formation. AB - Between December 1980 and December 1987, approximately 6,000 two-dimensional echocardiographic examinations were performed in our noninvasive cardiac laboratory. During this period, five cases of intra-atrial smoke-like echoes were diagnosed. The four patients with dense smoke-like echoes in the left atria all had echocardiographic evidence of severe mitral stenosis and thrombi in the left atrial cavity, both of which were confirmed at open-heart surgery. One patient with right-sided cardiomyopathy had echocardiographic evidence of dense smoke like echoes and thrombus in the right atrial cavity. One of our five patients was receiving anticoagulant therapy, and none had a history of thromboembolism. We conclude that using conventional two-dimensional echocardiographic techniques, smoke-like echoes in the atria are a very infrequent finding and are very commonly associated with formation of thrombi. PMID- 2924624 TI - Chronic cavitary histoplasmosis. Failure of oral treatment with ketoconazole. AB - Ketoconazole appears to be a safe drug in the treatment of chronic cavitary histoplasmosis. Primary failure and relapse have been described, requiring amphotericin B, even after long therapy with ketoconazole. Four typical cases are presented. We caution about such potential failures and stress the importance of close observation of patients begun on therapy with ketoconazole for chronic cavitary histoplasmosis. PMID- 2924625 TI - Nd-YAG laser-induced endobronchial burn. Management and long-term follow-up. AB - Endobronchial fires are a rare complication of Nd-YAG laser photoresection. Short term morbidity is secondary to sloughing mucosa and mucous plugging. Aggressive pulmonary hygiene, including frequent bronchoscopies and possibly a tracheostomy, may be required. The major long-term complication is obstruction of the airways from granulation tissue. Long-term follow-up is required to evaluate and treat clinically significant granulation tissue in the airways. PMID- 2924626 TI - Failure of corticosteroid therapy to prevent induction of ventricular tachycardia in sarcoidosis. AB - Programmed ventricular stimulation was performed in a patient with sarcoidosis who exhibited an episode of sustained ventricular tachycardia. Sustained rapid ventricular tachyarrhythmias requiring cardioversion for termination were induced by double right ventricular apical extrastimuli during control, and treatment with disopyramide, quinidine, and fluocortolone. In contrast, only four repetitive ventricular complexes were induced during combined therapy with quinidine, mexiletine and amiodarone. While receiving the latter regimen, the patient has been asymptomatic during 28 months of follow-up. PMID- 2924627 TI - Chronic cough as the presenting symptom of oculopharyngeal muscular dystrophy. AB - A patient had chronic, persistent cough as the presenting symptom of the neuromuscular disorder oculopharyngeal dystrophy (OPD). The presence of a significant smoking history initially resulted in the cough incorrectly being attributed to COPD. By using a systematic diagnostic approach, the correct etiology was determined. PMID- 2924628 TI - Blunt chest trauma. Extrapericardial cardiac tamponade by a mediastinal hematoma. AB - Mediastinal hematoma resulting from blunt chest trauma can cause compression of the right ventricle and extrapericardial cardiac tamponade. The diagnosis in this instance was aided by conventional two-dimensional echocardiography in addition to hemodynamic measurements. The atypical aspects of this form of cardiac tamponade are discussed. PMID- 2924629 TI - ARDS associated with boutonneuse fever. AB - The adult respiratory disease syndrome is associated with multiple disorders. At least one of the rickettsial diseases, RMSF, has been reported to be associated with noncardiogenic pulmonary edema. We report herein another rickettsial disease, boutonneuse fever, which is produced by Rickettsia conorii and is usually a mild disease, that in our patient was associated with ARDS. PMID- 2924630 TI - Prolongation of ventricular depolarization. ECG manifestation of mexiletine toxicity. AB - Mexiletine is a type 1B antiarrhythmic drug similar to lidocaine. Prolongation of ventricular depolarization has not been previously reported with the usual oral dosage of mexiletine. We describe a patient with renal failure and heart failure on low-dose oral therapy who developed mexiletine toxicity, which was manifested by ECG prolongation of ventricular depolarization. This was confirmed by elevated plasma concentration of mexiletine. This case illustrates that contrary to the usual belief, mexiletine pharmacokinetics are altered by renal failure. It is important to monitor mexiletine therapy by plasma levels in patients with impaired renal function to avoid mexiletine toxicity. PMID- 2924631 TI - Breakage and detachment of an Abrams needle in the pleural cavity during performance of a pleural biopsy. AB - This is the report of a case of breakage and detachment in the pleural cavity of the tip of a nearly new Abrams needle during performance of a pleural biopsy. We have not found any reference in the literature to similar accidents and do not know what later complications may be produced by the metal body in the pleural cavity. In this case, there have been no complications 12 months after the incident. PMID- 2924632 TI - Giant right atrial thrombus in Noonan syndrome combined with Eisenmenger's complex. AB - A 54-year-old woman with the Noonan syndrome was admitted with congestive heart failure and a giant right atrial thrombus with atrial septal defect detected by two-dimensional echocardiography. The thrombus vanished on oral anticoagulant therapy with warfarin. The thrombus is considered to result from hemostasis in the right atrium due to congestive heart failure and to her specific skeletal characteristics. This report describes the first case of Noonan syndrome with right atrial thrombus. PMID- 2924633 TI - Long-standing indolent blastomycosis at internal opening of tracheostomy. AB - An unusual case of long-standing endotracheal blastomycosis caused recurrent airway obstruction at a tracheostomy site. PMID- 2924634 TI - Bilateral extrapleural effusions complicating bilateral pneumonia. AB - In the case reported herein a patient developed bilateral pneumonia and septic shock and subsequently developed bilateral effusions. Chest roentgenograms, computed tomograms, and findings from analysis of the fluid within the chest were consistent with typical empyemas. When surgical decortication was attempted, the effusions were found to be anatomically extrapleural. Symptomatic improvement was noted following debridement. PMID- 2924635 TI - Iatrogenic or patient-induced? PMID- 2924636 TI - Balloons. PMID- 2924637 TI - PA catheter measures in lung injury. PMID- 2924638 TI - Long-term antiarrhythmia therapy. PMID- 2924639 TI - Sputum retention. PMID- 2924640 TI - Diminished translucency, a common roentgenographic feature of tropical pulmonary eosinophilia. PMID- 2924641 TI - The jackknife technique in statistical analysis. PMID- 2924642 TI - Adolescent child molesters: clinical observations. AB - Clinical assessments of 29 male adolescent child molesters referred to the Toronto Family Court Clinic showed that many were socially isolated, had chronic learning problems and had been maladjusted prior to committing their sexual offenses. The roles of drug and alcohol abuse, past sexual victimization, antisocial traits, disinhibition, peer-group influence, psychopathology and sexual deviance, alone or in various combinations, as causal factors for these boys' sexual offenses are discussed in view of previous studies and illustrated by case vignettes. PMID- 2924643 TI - Adolescents help themselves by helping others. PMID- 2924644 TI - Preventing infant mortality: an investment in the nation's future. PMID- 2924645 TI - Head Start/IBM Partnership. Computers and preschoolers. PMID- 2924646 TI - Indian child welfare: a status report. PMID- 2924647 TI - Networking on a shoestring. PMID- 2924648 TI - Specialized foster family care. A community-based program for children with special needs. PMID- 2924649 TI - Advocacy and ombudswork for children: implications of the Israeli experience. AB - Israel's establishment of what is to be the first in a network of child advocacy councils is discussed in relation to child advocacy efforts in the United States. The work and structure of the Jerusalem Children's Council and its Ombudsman for Children is described. It is suggested that Israel's experience in establishing a well-functioning local child advocacy council provides a model for implementing the recommendation of the Joint Commission on the Mental Health of Children to establish a network of local child advocacy councils in the United States. PMID- 2924650 TI - Child abuse in Korea. AB - Many parents in Korea approve of discipline by the rod. In fact, physical punishment of children has been regarded in Korea as a family affair rather than a social issue. Today, however, it is winning social attention in that it can become a form of domestic or social violence that can adversely affect the whole society as well as the family and individual. PMID- 2924651 TI - Adolescent pregnancy: standards and services in Finland. AB - Finland's adolescent pregnancy rate is lower than that of many comparable nations. The author examines Finnish standards and services on adolescent pregnancy, and results of a survey of adolescent sexual behaviors and attitudes. PMID- 2924652 TI - Treatment of delinquent youth in Finland. AB - Finnish law provides both protections and punishments for juvenile offenders, much of it dependent on the offender's age. A recently initiated mediation program is attempting to provide an alternative way to deal with crimes and conflicts, and to increase community understanding and tolerance. PMID- 2924653 TI - Causal reasoning and inference making in judging the importance of story statements. AB - The present study investigated the development of the ability to judge the importance of story statements on the basis of their causal properties. Key statements were varied with respect to 2 factors: in terms of the number of their causal relations, and in terms of the kinds of relations they had. Relations were either intraepisodic, that is, connecting statements in the same episode, or interepisodic, that is, connecting statements in different episodes. Children 8, 11, 14, and 18 years of age judged the importance of the statements. Children in all 4 age groups judged statements with many intraepisodic causal relations as more important than statements with few such relations. Only children 11 years and older judged statements as more important when they had interepisodic relations than when they did not. Thus, although young children may be sensitive to quantitative aspects of a statement's relational role within an episode, they may not be as aware of qualitative, that is, structural, differences between kinds of relations. Answers to why questions confirmed these patterns. Older children more often gave answers that crossed episodic boundaries than did the younger children. These findings may reflect age-related differences in children's ability to infer relations between statements and to integrate the information contained in stories. They also attest to the central role that causal inferences play in the interpretation of what is important information in stories. PMID- 2924654 TI - Children's use of a verbal-nonverbal consistency principle to infer truth and lying. AB - Children's use of a verbal-nonverbal consistency principle to infer truth and lying was investigated in 2 experiments. In Experiment 1, kindergarten (5-year olds), second- (7-year-olds), and fourth-grade (9-year-olds) children judged the truthfulness of stimulus persons whose verbal communication and nonverbal communication varied in valence (positive, neutral, and negative). In Experiment 2, children from the same 3 grades were presented part of the verbal communications on audiotape and a similar set of general verbal communications. They were asked to predict what facial expression the speaker would show if he or she was telling the truth or lying. The findings yielded by both experiments indicated that the use of the verbal-nonverbal consistency principle increased with age. Use of that principle was demonstrated by fourth grade children who judged that telling the truth, as opposed to lying, was shown by a consistency between the affective valence of the verbal and the nonverbal communications. PMID- 2924655 TI - Continuity and change in intrafamilial agreement in beliefs concerning the adolescent: a follow-up study. AB - In a 2-year follow-up investigation of parent-child agreement in beliefs concerning the child and of the child's awareness of parental beliefs in families with children in transition to early (ages 10-11 to 12-13) and mid-adolescence (ages 15-16 to 17-18), 42 families were reinterviewed with the Family Belief Interview Schedule. Major results indicated that over the follow-up interval: (1) accuracy of the child's prediction of parental beliefs increased sharply between 10-11 and 12-13 but not between 15-16 and 17-18 years; (2) congruence of both mothers' and fathers' beliefs with the child's self-beliefs increased; and (3) between families, overall levels of intrafamilial agreement in belief concerning the child remained remarkably stable. Findings support the notion that changes in adolescents' understanding of their own development and of their changing relationships to parents occur within a framework of overall consistency in level of intrafamilial agreement in belief. PMID- 2924656 TI - Emotional autonomy versus detachment: revisiting the vicissitudes of adolescence and young adulthood. AB - 3 studies reexamine Steinberg and Silverberg's construct of "emotional autonomy" (EA) in adolescent and young adult samples. We argue that rather than measuring either autonomy or independence, EA represents emotional detachment from parents. In Study 1, EA is shown to be negatively associated with early adolescents' (n = 148) reported quality of attachment to parents, but not to friends. In Study 2, EA is shown to be positively related to experienced parental rejection but largely unrelated to perceived independence-support in a high school sample (n = 193). In Study 3, EA in young adults (n = 104) is inversely related to measures of family cohesion, parental acceptance, independence support, and self-perceived lovability. Finally, a projective measure of parental nurturance taken by a subsample of subjects (n = 58) was associated negatively with EA but positively with perceived lovability. Discussion concerns the conceptualization of attachment versus detachment, dependence, and autonomy in theories of adolescence. PMID- 2924657 TI - The effects of object orientation and object type on children's interpretation of the word big. AB - Previous research indicates that preschool children have persistent difficulty interpreting big: 4-5-year-olds typically interpret big to mean tall, and 3-year olds fail to use any consistent interpretation. We propose that children's interpretation may vary depending on 2 contextual factors: type of object and orientation of object. 40 children (ages 3 and 5) each saw 35 pairs of items and, for each pair, were asked to point to "the big one." Type of object was varied by showing each child 3 kinds of objects: "people," "brownies," and rectangles. Orientation of object was varied by presenting objects either standing perpendicular to the tabletop (vertical condition) or lying flat on the tabletop (horizontal condition). Older children relied on height more consistently than younger children, all subjects relied on area more often in the horizontal condition than in the vertical condition, and 3-year-olds relied on height more when judging the bigness of people than of rectangles matched for size. Taken together, these results demonstrate that contextual factors clearly influence children's responses. These results demonstrate the interplay of cognitive and semantic factors in the process of semantic development. PMID- 2924658 TI - Establishing word-object relations: a first step. AB - This work explores how infants in the early phases of acquiring language come to establish an initial mapping between objects and their labels. If infants are biased to attend more to objects in the presence of language, that could help them to note word-object object pairings. To test this, a first study compared how long 18 10-14-month-old infants looked at unfamiliar toys when labeling phrases accompanied their presentation, versus when no labeling phrases were provided. As predicted, labeling the toys increased infants' attention to them. A second study examined whether the presence of labeling phrases increased infants' attention to objects over and above what pointing, a powerful nonlinguistic method for directing infants' attention, could accomplish on its own. 22 infants from 2 age groups (10-14- and 17-20-month-olds) were shown pairs of unfamiliar toys in 2 situations: (a) in a pointing alone condition, where the experimenter pointed a number of times at one of the toys, and (b) in a labeling + pointing condition, where the experimenter labeled the target toy while pointing to it. While the pointing occurred, infants looked just as long at the target toy whether or not it was labeled. During a subsequent play period in which no labels were uttered, however, infants gazed longer at the target toys that had been labeled than at those that had not. Thus language can increase infants' attention to objects beyond the time that labeling actually occurs. These studies do not pinpoint which aspects of labeling behavior contribute to the attentional facilitation effect that was observed. In any case, however, this tendency for language to sustain infants' attention to objects may help them learn the mappings between words and objects. PMID- 2924659 TI - Children's integration of facial and situational cues to emotion. AB - Children at 4 age levels (3-5, 6-7, 8-9, and 10-12 years) were shown a series of pictures in which facial and situational cues were (a) congruent, (b) conflicting, or (c) presented alone. Children rated the type (happy or sad) and intensity of the emotion felt by each character. Developmental changes in the relative weights assigned to facial and situational cues were examined using Anderson's information integration approach. The results showed that children's reliance on situational cues increased with age, but their reliance on facial expression decreased with age. Analysis of individual children's ratings indicated a developmental increase in the tendency to integrate facial and situational cues. Children's ability to resolve the conflicting cues (through stories) also increased with age, but there were no age differences in the types of resolutions used. At all age levels, children were less likely to resolve pictures involving an inconsistent positive expression than pictures showing an inconsistent negative expression. PMID- 2924660 TI - Toddlers' emerging ways of achieving social coordinations with a peer. AB - 14 peer dyads were observed longitudinally at 16, 20, 24, 28, and 32 months to assess developmental changes in social coordinations (both action-to-action thematic relations and extended games). Each child's movements through the playroom, actions upon play material, vocalizations, verbalizations, and gestures were coded for their relation to the concurrent or immediately prior behavior of the peer: Unrelated, Tangential, Coordinated, Interfering. There was a marked increase with age in acts coordinated with those of a peer, and imitations of the peer's nonverbal actions accounted for most of the developmental change. The use of words to direct the peer in a coordinated way increased with age but remained infrequent. Developmental change in the frequency of games paralleled that for imitative acts, and imitative acts both established and set the theme for most of the games. Thus, imitating another's nonverbal actions is a core behavioral strategy for achieving social coordinations during the developmental period preceding reliance on verbal communication in peer interaction. PMID- 2924661 TI - Maternal self-efficacy and infant attachment: integrating physiology, perceptions, and behavior. AB - 48 mothers of 5-month-old infants were asked to estimate their control over the termination of an infant cry in a laboratory-simulated child-care task. Mothers who greatly overestimated their control differed from low or moderate "illusion of-control" mothers by exhibiting a depression-prone attributional style, a depressed mood state, perceiving the father as participating less in child care, and responding to impending infant cries with heart-rate acceleration characteristic of aversive conditioning. At age 16 months, 40 of the mother infant pairs participated in the Ainsworth Strange Situation. Insecure infant attachment at 16 months was associated with maternal perception of overcontrol, depressed mood state, and aversive conditioning to the impending cry in the laboratory task at the 5-month period. PMID- 2924662 TI - Maternal separation in bonnet monkey infants: altered attachment and social support. AB - Maternal separation in young pigtail (M. nemestrina) monkeys results in an agitation-depression reaction that is a useful animal model of the behavioral and physiological consequences and separation and loss experiences in humans. In this study, 5 social-group-living bonnet (M. radiata) monkey infants were separated from their mothers for 4 days, and behavioral, physiological, and sleep-pattern changes were monitored. Behavioral and physiological changes were consistent with an agitation reaction. There was evidence of depression in both behavioral and physiological measures; these changes were not as pronounced as in pigtail infants, however. All infants were adopted by another adult female during separation. Our findings suggest that, in bonnet monkey infants, adoption by a female within the social group ameliorates the response to loss. PMID- 2924663 TI - Continuity and discontinuity in maternal sensitivity at 6, 24, and 42 months in a high-risk sample. AB - Continuity and discontinuity in maternal sensitivity from 6 and 24 months to 42 months were examined in a sample of 135 disadvantaged mothers and their firstborn children. Sensitivity at 6 and 24 months accounted for 18% of the variance in 42 month maternal sensitivity for boys, 14% for girls. Discontinuity was examined using residual scores. Less maternal sensitivity than predicted was related to stressful environmental and child characteristics for both boys and girls, while greater sensitivity than predicted was related to mothers' experiences of emotional support, girls' positive individual characteristics, and boys who were seen as unengaged. PMID- 2924664 TI - Stable individual differences in developmentally changing preterm infants: a replicated study. AB - In a longitudinal study with the Neurobehavioral Maturity Assessment (NB-MAP), developmental changes and stability of individual differences were assessed in 2 independent samples of preterm infants ranging from 32 weeks conceptional age to term. Individual stability of response was assessed using regression analysis with repeated measures on subjects. The large majority of the functions tested showed highly significant developmental gains with age and highly significant individual stability of performance across age. These findings replicated well across the 2 cohorts. The results are discussed in the light of the neurobiological stage of development of preterm infants during the last 8 weeks prior to term. PMID- 2924665 TI - Which homes? A response to Scarr and McCartney (1988). AB - Scarr and McCartney's (1988) Bermudian study shows the futility of using the Verbal Interaction Project's Mother-Child Home Program (MCHP) to prevent later educational disadvantage in preschoolers who are not at risk for such disadvantage. Recently published research is cited to support a conclusion that poverty alone does not predict school disadvantage so much as poor parents frequently having low motivation and less than high school graduation, unlike the Bermudian sample. Significant positive school effects through eighth grade are noted to have occurred when the MCHP was used with Massachusetts preschoolers who were socioeconomically at risk for educational disadvantage and thus were of lower SES than the advantaged Bermudian children. Methodological issues are also discussed. PMID- 2924666 TI - [Symposium: Thrombosis and embolism. The value of fraxiparin in the prevention of postoperative thromboembolism. 28-29 October 1988, Cologne. Abstracts]. PMID- 2924667 TI - Long-term functional analysis of the ileoanal reservoir. AB - Since November 1980, 180 patients underwent abdominal colectomy, rectal mucosectomy, ileoanal reservoir construction, and ileoanal anastomosis at the authors' institutions. One hundred twenty-nine patients had restoration of intestinal continuity before the end of 1986. One hundred fourteen of these patients (88 percent) were available for follow-up at a mean length of time of 5.0 years from ileostomy closure (range, 16 to 88 months). The mean number of pouch evacuations was 5.4 +/- 2.5 during the day (range, 1 to 12) and 1.5 +/- 1.0 at night (range, 0 to 6). Ninety-one percent of patients reported perfect or almost perfect daytime continence, and 74 percent found this true at night. Sixty three percent of patients believed their pouch function continued to improve over many years. Ninety-five percent of patients questioned would choose an ileoanal reservoir again instead of a permanent ileostomy. This long-term assessment of the function of the ileoanal reservoir confirms that it is a viable, although not perfect, option in the management of ulcerative colitis and familial adenomatous polyposis. PMID- 2924668 TI - International colorectal carcinoma staging and grading. AB - Pathologic (Dukes) and clinicopathologic staging systems (Australian and TNM) are all used for the staging of colorectal cancer. Many modifications of the systems, with different standards of evidence, are currently used for a variety of purposes. It is not yet possible to readily exchange data from one staging system to another because of the lack of uniform anatomic and pathologic subdivisions. It would also be an advantage if staging systems more confidently predicted potential for cure. It is proposed that the TNM based system be modified to satisfy these requirements. Modifications identify common ground between the various systems, use prognostic variables shown to be significant by multivariate analyses, and introduce an abbreviated form of tumor grading. Grading improves prediction of cure and allows standardization of the composition of stages and substages because distant metastatic potential is shown to be related to the presence of high grade. The modifications are considered necessary and appropriate for epidemiologic and clinical studies. PMID- 2924669 TI - Extended resection for locally advanced primary adenocarcinoma of the rectum. AB - To determine the perioperative mortality and morbidity and the longterm prognosis of patients undergoing extended pelvic resections for localized advanced primary adenocarcinoma of the rectum, the authors reviewed their experience with 65 patients operated on between 1956 and 1984. Local invasion without distant metastasis was present in all patients at operation and en bloc resection of all involved organs was performed with intent of cure. Average age at operation was 61 years; 15 (23 percent) were men and 50 (77 percent) were women. Operations included abdominoperineal resection in 37 patients (57 percent), low anterior resection in 20 patients (31 percent), and Hartmann procedure in 8 patients (12 percent). Additionally, 34 of 42 women (81 percent) with intact uteri underwent en bloc hysterectomy, 37 of 48 women (77 percent) with intact ovaries had oophorectomy, and 25 of 50 women (50 percent) had partial vaginal resection. Seventeen of the 65 patients (26 percent) had a cystectomy, and 2 patients had a portion of small intestine resected in continuity with their tumor. Pathologic examination revealed lymph node involvement in 29 patients (45 percent) and histologic confirmation of adjacent organ extension in 37 patients (57 percent). There were no perioperative deaths, the average survival was 5.7 years, and 25 patients (38 percent) were alive after a mean follow-up period of 9.3 years. Overall five-year survival was 52 percent. Forty patients died during the follow up period, with 26 (65 percent) of the deaths attributable to either recurrent carcinoma (25 patients) or a new primary lesion (1 patient). The cumulative probability of tumor recurrence at five years was 39 percent. PMID- 2924670 TI - Complications of colostomies. AB - One hundred twenty-six patients underwent 130 end colostomies, 44 for benign and 86 for malignant disease, and were followed for an average of 35 months. The left or sigmoid colon was used in 99 and the transverse colon in 31. Stomas were made electively in 98 patients and urgently in 32. Seventy-six stomas were brought out through the incision and 54 from separate sites. There were 69 complications in 55 patients (44 percent) including 11 strictures, 9 wound infections, 14 hernias, 9 small-bowel obstructions, 4 prolapses, 2 abscesses, 1 peristomal fistula, 17 skin erosions, and 2 poor stoma locations. Fifteen complications required reoperation. Five of these procedures included stoma revision. Total numbers of complications were not related to the stoma site, the disease process, the urgency of the procedure, or the segment of colon used. Wound infections, however, were increased in urgently made stomas. The incidence of hernia was equivalent in stomas brought out through the incision or at a separate site. Forty-one patients (30 percent) had 43 colostomies closed an average of 3.5 months after creation. Thirteen patients had 14 complications--5 wound infections, 6 hernias, 2 small-bowel obstructions, and 1 rectovaginal fistula. One patient died. Four patients required reoperation. There were no anastomotic leaks. Complications were equivalent in Hartmann closures and transverse colostomy closures. Complications were similar in stomas created for cancer and those created for diverticular disease. PMID- 2924671 TI - Preoperative hyperthermochemoradiotherapy for patients with rectal cancer. AB - Preoperative hyperthermochemoradiotherapy (HCR therapy), consists of a combination of hyperthermia at 42 to 45 degrees C for 40 minutes (2 times per week for two weeks), 5-fluorouracil (5-FU) intravenously (total, 1000 to 1750 mg), and a total of 30 Gy irradiation. The therapy was prescribed preoperatively most recently for 11 patients with rectal cancer. The authors used a radiofrequency system involving an endotract electrode with thermosensors for the hyperthermia. The effectiveness of preoperative HCR therapy was evaluated by irrigography, fiberscopy, and histopathologic findings in the resected specimens. Reduction in tumor size and amount was evident in all patients, with all modes of assessment. Histologically, no or only a few viable cancer cells were seen in the resected specimens in six patients, a small number of viable cancer cells in three, and a fair number of viable cancer cells in two patients; there were no complications. This method of treatment is expected to play an important role in the interdisciplinary treatment for rectal cancer. PMID- 2924672 TI - Ulcerative colitis: electron microscopic studies with special reference to development of crypt abscesses. AB - Electron microscopy of the colonic mucosa was performed in 33 patients with acute ulcerative colitis. The process of the development of crypt abscesses was studied. Inflammatory cells migrated intercellularly from the lamina propria and did not destruct the neighboring epithelial cells. Abnormal maturation of the epithelial cells was observed. Loose connection and separation of immature epithelial cells may promote migration of inflammatory cells. PMID- 2924673 TI - Transcolonoscopic decompression of sigmoid volvulus. AB - Colonoscopy may decompress a sigmoid volvulus above the reach of a rigid sigmoidoscope. Intraluminal stenting to prevent early recurrence can be accomplished using flexible plastic tubing passed over the colonoscope. PMID- 2924674 TI - A new approach to rectal anastomotic stricture. AB - A technique is presented that can serve as a solution for localized postoperative rectal stricture. This procedure was used after the failure of manual and instrumental dilatations. It consisted of cutting the prominent plication of the stricture, using the EEA stapler. Five patients successfully underwent this operation without morbidity or mortality, three after very low anterior resection and two after total colectomy, mucosal proctectomy, and ileoanal anastomosis. PMID- 2924675 TI - Anal duct carcinoma. PMID- 2924676 TI - Stenosis due to Crohn's disease. PMID- 2924677 TI - Camp nursing--a rewarding change of pace. AB - Burnout and nursing shortage are two negative realities in today's health care system. If burnout can be averted, retention will increase and the shortage will be less severe. Camp nursing provides an appealing option for critical care nurses from adult or pediatric intensive care units who need a temporary change of pace. PMID- 2924678 TI - Nursing opportunities: advice nurses give their children. PMID- 2924679 TI - Legal aspects of standards of practice. AB - In the article Developing Unit-Specific Standards in the November/December 1988 issue of DCCN, the authors described techniques for developing and implementing unit-specific standards of practice in critical care. Here the nurse-attorney author adds another perspective, a legal one. This author suggests ways to word standards of practice so that they will be more useful in defending the nurse and the hospital in any potential negligence claims. PMID- 2924680 TI - Technicians in critical care: training, supervisory, and legal aspects. AB - An extra pair of hands is a precious commodity because of today's nursing shortage. Should technicians without nursing credentials be assigned to fulfill the role of nurses in critical care areas? Many have already voiced their opinions against the Registered Care Technologist (RCT) proposal of the American Medical Association (AMA), but it is time to examine the larger issue: the broad use of technicians in critical care. This author clarifies important factors regarding the use of technicians in critical care. PMID- 2924681 TI - Developing an arrhythmia course for obstetric nurses. AB - The need has increased for high-risk obstetric nurses to interpret cardiac rhythms, owing to the potential cardiovascular side-effects of tocolytic therapy in premature labor. The cardiovascular critical care nurse, educator, and clinical specialist are important to obstetric nurses as consultants for arrhythmia interpretation. These authors describe how to plan, develop, and implement an arrhythmia course for staff nurses working in obstetric units. PMID- 2924682 TI - Avoiding territorialism in response to RCTs. PMID- 2924683 TI - Aortic valvuloplasty: potential nursing diagnoses. AB - The use of transluminal balloon angioplasty has become widespread in the treatment of cardiovascular diseases. Since critical care nurses are responsible for the assessment and management after the procedure in the critical care unit, the authors provide information on the pathophysiology and potential nursing diagnoses for these patients. In this way, the critical care nurse can support the patient before, during, and after the procedure. PMID- 2924684 TI - Obstructive sleep apnea: preventing complications. AB - The patient with an acute episode of obstructive sleep apnea requires critical nursing care to prevent or manage respiratory failure. The author describes monitoring and preventive nursing measures for these patients. PMID- 2924685 TI - The pregnant woman with a myocardial infarction: nursing diagnosis. AB - Critical care nurses in emergency, cardiac, or medical intensive care units may care for women who have experienced a myocardial infarction during pregnancy. Nursing management of the pregnant patient with a myocardial infarction (MI) requires an understanding of the normal physiology of pregnancy, the deviations from health with an MI, and an ability to integrate this knowledge to provide skillful care to unique and very ill patients. Here the authors describe caring for a pregnant patient in cardiac care, while a later article in this tissue focuses on the critical care nurse's role in teaching obstetric nurses arrhythmia interpretation when the patient remains on an obstetric unit. Collaboration between the critical care nurse and obstetric nurse is essential to care for these complex patients. PMID- 2924686 TI - Specific oligodeoxynucleotide probes obtained through RNA sequencing. AB - By combining several established techniques we developed a method to test the specificity of mixed oligodeoxynucleotide hybridization probes and to provide the information for the design of long nondegenerate, and therefore more specific probes. Mixed oligodeoxynucleotide probes derived from known peptide sequences are first used to initiate primer extension reactions with poly(A)+RNA as template in the presence of three dNTPs and one ddNTP to generate cDNA transcripts of defined lengths. Comparing the lengths of the cDNA transcripts with the possible nucleic acid sequence coding for the known oligopeptide indicates whether the oligodeoxynucleotide mix hybridizes predominantly to the RNA of interest. In a second step, the oligodeoxynucleotide mix with the highest specificity is used for indirect RNA sequence analysis. This confirms the specificity of the probe and provides information to design a long, highly specific oligodeoxynucleotide probe for the gene of interest. This simple two step-procedure helps to circumvent the time-consuming procedures of subcloning and sequencing of cross-hybridizing fragments. PMID- 2924688 TI - Structure of human angiotensinogen gene. AB - A cDNA clone encoding human angiotensinogen was isolated from a cDNA library prepared from human liver mRNA and used to isolate the angiotensinogen gene. The complete exon sequence of this gene together with extensive intron and flanking sequences are reported. The human angiotensinogen gene contains five exons interrupted by four intervening sequences. We compared the intron-exon structure of this human gene with that of the rat gene or the genes coding for proteins such as alpha 1-antitrypsin and antithrombin III, whose primary amino acid sequences show similarities. The human angiotensinogen gene shows identical organization with the alpha 1-antitrypsin gene, but is different from the antithrombin III gene. The 5'-flanking sequence (-500 to -1 bp) of the human angiotensinogen gene was examined for hormone regulatory elements (HRE), which may be implicated in the interaction with the hormone receptor complexes. PMID- 2924687 TI - Structure and organization of the gene encoding human pulmonary surfactant proteolipid SP-B. AB - Human pulmonary surfactant proteolipid SP-B arises by proteolytic processing of a 42,000-dalton precursor. The active proteolipid SP-B is one of two small hydrophobic proteins identified in surfactant that impart surface-active properties to surfactant phospholipids. We report the isolation and characterization of complete SP-B cDNA from a human lung cDNA library. The cDNA was used to isolate the gene encoding the SP-B precursor from a lambda EMBL3 library of human embryonic kidney DNA. The entire SP-B gene was sequenced and is approximately 9.5 kb long, with 11 exons and 10 introns including a large 823 nucleotide 3' untranslated exon. The sequence derived from the exons differs from the cDNA sequence at 3 positions out of 2001, only one of which is in the translated region. Direct RNA sequencing indicated that the 5' untranslated region is only 14 nucleotides long. A number of putative regulatory elements were found upstream of the SP-B gene, including a GC box and several putative cAMP and glucocorticoid receptor binding sites. Several Alu repeats and a region of potential Z-DNA formation were found in the introns. Southern blotting of human genomic DNA probed with SP-B cDNA indicated the presence of only one SP-B gene in the human genome, and the gene was localized to chromosome 2. PMID- 2924689 TI - Usefulness of cardiovascular tests of autonomic function in asymptomatic diabetic patients. AB - A group of five cardiovascular tests of autonomic neural function was studied in 115 asymptomatic insulin-dependent diabetic patients and nine patients with symptoms of diabetic autonomic neuropathy. In the asymptomatic group, 34 patients had one or more abnormal test. R-R variation during deep breathing was most frequently abnormal, but reliance on this test alone to examine parasympathetic function would have missed 12 of the 34 abnormal patients. The two abnormal responses to isometric exercise in this group were probably false-positive results caused by poor patient effort. In the symptomatic patients, R-R variation during deep breathing was abnormal in all nine, the blood pressure response to standing was abnormal in seven, and the response to isometric exercise was abnormal in three. The blood pressure response to isometric exercise is uncomfortable, requires special equipment, and should probably be confined to the assessment of symptomatic patients in a specialist setting. PMID- 2924691 TI - [Effect of demographic changes on the case rate and days of care for hospitalized internal medicine patients]. AB - Using case categories at the Center for Internal Medicine of the Medical University at Lubeck and predictions of future population trends by the German Federal Statistical Office, likely future numbers of inpatients and days of hospital stay were calculated. Assuming other conditions remaining constant, an annual rise of 0.9% of medical cases is to be expected until the year 2005. An increase above this average is expected for cases of cardiovascular and respiratory disease and of malignant neoplasms, while it will be below average for renal or gastrointestinal diseases. These data are similar to comparable projections made, on the basis of Federal statistics, of hospital cases registered with local health insurance schemes. In addition they indicate an increase of 3% for all non-paediatric admissions up to 2005. PMID- 2924690 TI - [Basic therapy of chronic heart failure with digitalis or diuretics?]. AB - Sixteen patients in heart failure and sinus rhythm were, after a four-week treatment-free period, randomly assigned to receive, for four to six weeks, either a diuretic combination (hydrochlorothiazide + triamterene) or a digitalis glycoside. Subsequently the treatment was exchanged between the two groups. Without treatment nine patients were in stage II (New York Heart Association classification), seven in stage III. Pulmonary wedge pressure at rest was 27 +/- 14, on exercise 32 +/- 8 mm Hg, cardiac output 5.3 +/- 1.0 at rest and 7.8 +/- 2.3 l/min on exercise. Digitalis glycosides improved symptoms by one stage in three of 16 patients. All objective measures showed slight but not significant improvement. Diuretic treatment improved symptoms in five patients, while heart size and echocardiographically measured ventricular volume decreased slightly. Cardiac output decreased at rest, but not significantly, and on exercise not at all. Pulmonary arterial pressure (21 +/- 9 mm Hg), pulmonary wedge pressure (13 +/- 7 mm Hg) and pulmonary artery pressure on exercise (39 +/- 11 mm Hg) were significantly lower on diuretics than without treatment. The results support the primary use of diuretics in the treatment of chronic heart failure. PMID- 2924692 TI - [Endoscopic balloon dilatation of benign choledochal stenosis]. AB - A 68-year-old woman was admitted because of septicaemia after cardiac valve replacement. Cause of the septicaemia was a proximal filiform common bile duct stenosis with recurrent gallstones and secondary cholangitis. A single pneumatic balloon dilatation widened the common bile duct. At the same time, specific antibiotic treatment cured the septicaemia. Nine months later no further dilatation has been necessary. PMID- 2924693 TI - [Treatment of metastatic adrenal carcinoma with suramin]. AB - A right adrenocortical carcinoma (weighing 978 g) was removed from a 45-year-old man in April 1986, the tumour bed then being irradiated with 40 Gy. Subsequently discovered multiple lung metastases were treated with cisplatin, etoposide and bleomycin, without improvement. Treatment with mitotane (Lysodren) was also without effect and had to be discontinued because of severe side effects. Treatment with suramin (Germanin) was begun in August 1987. After a loading dose of 10.7 g for six weeks the lung metastases regressed almost completely. But lung metastases were again demonstrated in January 1988 during a low-dose maintenance regimen of suramin. Increased dosage arrested further growth, but achieved no regression of the metastases. The patient died unexpectedly in April 1988 of acute circulatory failure. Suramin administration had been discontinued six weeks earlier because of bronchopneumonia and general deterioration. Thrombocytopenia, coagulation disorders and moderate proteinuria were the side effects of suramin treatment. PMID- 2924694 TI - [Release of hospital discharge reports to insurance companies]. PMID- 2924695 TI - [HIV infection with a serological variant]. PMID- 2924696 TI - [Experiences with highly concentrated heparin preparations]. PMID- 2924697 TI - [Upper gastrointestinal bleeding from ulcer: reduction of mortality by early elective surgical therapy of patients at risk]. AB - Amount, activity and localisation of bleeding, as well as patient-specific risk factors were used to define a group of patients at risk who were treated electively early by surgical intervention, within the first 24-36 hours after onset of the primary bleeding. 147 patients were included in the study between 1982 and 1988, a bleeding gastric ulcer being present in 67 (46%), a bleeding prepyloric ulcer in 14 (9%), and a bleeding duodenal ulcer in 66 (45%). 135 (92%) patients had a bleeding activity of I and II in Forrest's classification. 94 patients were in the at risk group and underwent early selective surgical treatment. During the period of study 13 patients (8.8%) died, with a drastic reduction in mortality rate during the 1982-1988 period from 20 to 0%. Stoppage of bleeding was the aim of operative intervention; treatment of the ulcerative condition was undertaken in only 43%. Reduction of the mortality rate to zero is ascribed to the early treatment concept. PMID- 2924698 TI - [Quality of life after rectal resection or extirpation. A comparison using different measurement parameters]. AB - Two groups of 41 patients each who had undergone rectal resection or excision were questioned about the quality of their life an average of 4.3 or 3.8 years, respectively, after the operation. Three different measurements were obtained (Karnofsky, Grogono and Spitzer indexes). In addition, the patients provided a subjective estimate of the quality of their life. The quality of life was significantly better after resection than after excision, most clearly so according to the Grogono index, and this was also reflected in the patients' personal assessment. In males rectal excision frequently resulted in inferiority feelings, depression and disorders of sexual activity. Females found it easier to cope: they showed only minor differences in quality of life between resection and excision. Irrigation proved to be the best means of stoma care as far as quality of life was concerned. PMID- 2924699 TI - [Aseptic skin necrosis after subcutaneous injection of alpha interferon]. AB - Aseptic necrosis of the skin developed in two patients with HIV-associated disseminated Kaposi's sarcoma after subcutaneous injection of recombinant interferon-alpha. Both patients were given it at a daily dosage of 20 x 10(6) IU/m2 body surface area. One of the patients, after full remission had been achieved, received a reduced dosage of 3 x 10(6) IU/m2, twice weekly. The clinical picture and course of the changes were similar to those of embolia cutis medicamentosa (Nicolau's syndrome), which can occur after injection of various drugs, intended to be intramuscular but by mistake given intra-arterially. PMID- 2924701 TI - [Immunoscintigraphy and immunotherapy]. PMID- 2924700 TI - [Diseases caused by group G beta-hemolytic streptococci]. AB - Group G beta-haemolytic streptococci were isolated from two patients, one with life-threatening septicaemia and meningitis, the other with puerperal sepsis and endometritis. The bacteria were isolated by blood culture and from cerebrospinal fluid in one patient, and from cervical swabs and urine in the other. In both treatment with a cephalosporin followed by penicillin G promptly led to recovery. These cases may signal an increasing incidence of severe infections caused by group G beta-haemolytic streptococci. PMID- 2924702 TI - [Post-transfusion hepatitis]. PMID- 2924703 TI - [Pump-aided percutaneous transhepatic litholysis of gallstones]. PMID- 2924704 TI - [Chronic paranoid-hallucinatory psychosis as the initial manifestation of an HIV infection?]. AB - In a 36-year-old patient an acute onset of psychosis occurred, probably due to HIV infection. For one year HIV-infection with reduced T4/T8 ratio had been known without clinical manifestation (stage IV B of the CDC-classification). He developed chronic delusional hallucinations, which persisted for more than one year in spite of adequate psychoactive drug therapy. So far AIDS-related dementia has not become evident. Focal lesions caused by opportunistic infections or tumour were excluded by computed tomography and magnetic resonance imaging. The latter revealed several small lesions and the brain scan showed a nonhomogeneous pattern of cerebral blood flow. CSF-examination disclosed a mild lymphocytosis and raised protein concentration. A classification as an organic, HIV-induced delusional hallucination seems to be justified. PMID- 2924705 TI - [Proto-oncogene expression in human carcinomas of the stomach and in the gastric mucosa of rats exposed to N-methyl-N'-nitro-N-nitrosoguanidine-induced gastric carcinogenesis]. AB - The expression of c-Ha-ras-1, Ki-ras, N-ras, abl, src, fos and myc protooncogenes was analyzed in 13 cases of human gastric carcinomas. The transcriptional activity of both fos and myc protooncogenes was found to be disturbed in 47% and 42% of cases, respectively. An overexpression of fos protooncogenes as well as an appearance in some cases of atypical foc-mRNA transcripts were established. Only an elevation of the number of myc mRNA copies was observed. In one patient with gastric carcinoma a c-Ha-ras-1 overexpression was detected due to its amplification both in tumour tissues and in regional metastasis. The expression of other protooncogenes under investigation was similar to those found in normal gastric mucose. In addition, no differences in expression in protooncogenes mentioned above plus sis protooncogene were established in unchanged, premalignant and malignant stomach tissues in the course of N-methyl-N'-nitro-N nitrosoguanidin-induced carcinogenesis. PMID- 2924706 TI - [Morphometric characteristics and functional activity of the cells of Ehrlich ascites cancer found in different phases of the cell cycle]. AB - The Ehrlich ascites carcinoma cells at different interphase periods have been studied for dynamics of ultrastructural and morphometric characteristics and biochemical analysis of metabolism of the given cells has been made. A distinctive structure-function correlation detectable by stage coincidence in the re-structure with the cell metabolism alterations is shown. PMID- 2924707 TI - [DNA-bound lipids of the cells of Zajdela ascites hepatoma and of Ehrlich ascites cancer]. AB - DNA-bound neutral lipids (NL) and phospholipids (PL) were isolated and characterized from the Zajdel ascites hepatoma (ZAH) and Ehrlich ascites carcinoma (EAC) cells. The lipids are represented by light- and tightly bound components. It was shown, that the tumour DNA contained minor amount of NL (25, 17 micrograms and 16.87 micrograms per mg DNA, respectively) and of PL (4.54 micrograms and 5.36 micrograms per mg DNA, respectively, for ZAH and EAC). The composition of the tumour DNA-bound lipids was shown to differ from that of DNA bound lipids of liver and thymus of intact rats by the next parameters: NL/PL ratio is much more than one; increased content of FC; equal values of the three basic ratios--CE/FC, NL/PL, cholesterol/PL, presence of mono- and triglycerides. PMID- 2924708 TI - [Interaction of the plasma membranes of the cells of tumors metastasizing to the lungs with the target organ]. AB - Cells of lines of mice transplantable tumours metastasizing into the lung have been used: lung adenocarcinoma (AL), Lewis lung carcinoma (LL), melanoma B-16 (B 16), mammary tumour MMT-1 (MMT-1), malignant subline of L-cells (LS). Hybrid vesicles were obtained for each tumour. They contain fragments of cell plasmatic membranes (PM). It has been shown that AL-, LL-, LS- and B-16-liposomes were accumulated in lung, the trapping of AL- and LL-liposomes being higher than that of the other hybrid vesicles. Despite the similar dynamics and frequency of metastatic spreading into the lung for all tumours studied, no trapping of MMT-1 vesicles in the target-organ was observed. The role of specific interaction of tumour cells PM with the endothelium of the lung capillaries in the process of organotropic metastatic spreading is discussed. PMID- 2924709 TI - [Functional changes in the natural killer cells of patients with acute leukemia]. AB - The results of study of NKC activity (51Cr release assay, conjugate-forming and lytic activity) in healthy persons and patients with acute leukemia (AL) in active phase and in remission are presented. It has been shown that the depression of the NKC activity in acute phase of AL (6 times as low as in norm) and in remission (3 times as low as in norm) depended upon disturbances of the processes of conjugate formation, lytic and recycling activity. Correlation has been found between percentage of lytic conjugates and that of cytotoxicity. The increase of NKC activity in remission seemed to be due to tendency to normalization of functional state of NK-cells (conjugate-forming and recycling activity). PMID- 2924710 TI - [The expression of antigens, detectable with ICO-series monoclonal antibodies, on the surfaces of cells forming granulocyte and macrophage colonies in semiliquid agar]. AB - The expression of antigens on granulocyte-macrophagal colony-forming cells of patients with nonhematological diseases was studied. Treatment of bone marrow cells with murine monoclonal antibodies ICO-1 and ICO-11 led to statistically significant inhibition of the number of growing colonies. Monoclonal antibodies ICO-02, ICO-10, ICO-GM-1 and ICO-G-2 had no such effect. PMID- 2924711 TI - [Secretion of type-E prostaglandin by tumor cells of different degrees of malignancy when in contact with effectors of natural resistance]. AB - It was demonstrated that short-term contact of highly malignant tumour cells with NK-cells, neutrophils and macrophages induced rapid PGE secretion into the culture medium. PGE is detected in the culture fluids by the biological test based on inhibition of cytotoxic activity of NK-cells in standard cytotoxic tests. In the direct radioimmunoassay no PGE release was detected when low malignant tumour cells contact with effector cells of natural resistance system as well as after malignant tumour cell pretreatment with indomethacin. There was no increase in PGE secretion by the malignant tumour cells after their in vitro contact with red cells, normal hamster embryo cells and tumour cells of different origin. PMID- 2924712 TI - [Cytostatic action of the peritoneal cells of Syrian hamsters to transformed and tumor cells in vitro and its suppression by prostaglandin E2]. AB - High antitumour activity of Syrian hamster peritoneal cells (PC) is demonstrated in the cytostatic test in vitro. The cytostatic effect (CSE) of PC on hamster cell strains can be revealed at the very early stage (7 hours of cocultivation) and it remains stable during at least 24 hours. Single intraperitoneal injection of physiological (10(-9) M) or pharmacological (10(-7)) doses of prostaglandin E2 preparation leads to the prolonged and significant inhibition of CSE of PC. PMID- 2924713 TI - [Sensitivity to chemotherapeutic preparations of anthracycline-resistant strains of murine leukemia P388]. AB - P388 leukemia strains resistant to rubomycin and ruboxylnitroxyl derivative of rubomycin were studied for their drug sensitivity. The resistant strains exhibited cross resistance to anthracycline antibiotics, vinca alkaloids, actinomycin D, colchicine. The rubomycin-resistant strain gained significantly higher sensitivity (in comparison with the parent strain and the ruboxyl resistant strain) to six drugs: cisplatin, sarcolisin, dopan, thiophosphamide, degranol, 6-mercaptopurine. The karyotype of the ruboxyl-resistant cells was characterized by the presence of chromosome with homogeneously straining region (HSR). The alteration of the HSR-location was accompanied by the increase of chemotherapeutical sensitivity of the ruboxylresistant strain to the alkylating agents. PMID- 2924715 TI - [Effect of staphylococcal enterotoxin A on the development of Lewis lung carcinoma in mice]. AB - The effect of Staphylococcus aureus enterotoxin A (SEA) was studied for its effect on the development of the Lewis carcinoma in mice. It was shown that administration of SEA immediately after the appearance of the primary node in mice after transplantation of tumour cells led to insignificant inhibition of the node growth and a slight decrease of tumour metastasizing into the lungs. Inoculation of mice after the appearance of the primary node with 1/microgram of SEA 5 times a week significantly increased their survival rate. The lack of the marked effect of SEA appears to be associated with the disturbance of the immune interferon system functioning in tumour-bearing mice, since the production of serum interferon induced by SEA in mice with tumours was considerably lower than in the intact ones. PMID- 2924714 TI - [Decrease in the blood toxicity of antitumor preparations during enterosorption]. AB - It is shown that peroral administration of activated charcoal SCN in rats with subcutaneously grafted Guerin carcinoma and Svec erythroleucosis does not hamper the antitumoural action of cyclophosphamide, methotrexate, and carminomycin and provides a protective effect on the medullar haemopoiesis. PMID- 2924716 TI - Regulation of progesterone biosynthesis by estrogen during baboon pregnancy: placental mitochondrial cholesterol side-chain cleavage activity in antiestrogen (ethamoxytriphetol, MER-25)-treated baboons. AB - We determined whether the reduction in placental progesterone (P4) production observed after administration of the antiestrogen ethamoxytriphetol (MER-25) to pregnant baboons was associated with a decline in activity and/or content of the placental mitochondrial cholesterol side-chain cleavage system (P-450scc). Pregnant baboons (Papio anubis) were untreated (n = 9) or administered MER-25 (25 mg/kg BW, orally; n = 6) daily on days 140-170 of gestation (term = 184 days). Placentas were obtained by cesarean section on day 170 of gestation, and P-450scc activity and cytochrome P-450 content were determined on mitochondria-rich fractions. Administration of MER-25 to pregnant baboons resulted in a 40% reduction (P less than 0.01, by Student's t test) in the mean (+/- SE) peripheral serum P4 concentration (6.3 +/- 0.3 ng/ml) compared to that in untreated (10.4 +/ 0.3 ng/ml) baboons. P-450scc activity, as determined by formation of pregnenolone (P5) and P4 during a 30-min incubation (picomoles per mg protein), was 37% lower (P less than 0.01) in placental mitochondria obtained from MER-25 treated baboons (179.8 +/- 25.0) than in that from untreated (285.4 +/- 13.4) baboons. Mitochondrial cytochrome P-450 content, assessed by spectral analysis, was 28% lower (P less than 0.02) in antiestrogen-treated (46.7 +/- 2.1 pmol/mg protein) than in untreated (64.8 +/- 5.2 pmol/mg protein) baboons. The initial (time zero) free cholesterol content (nanomoles per mg protein) of mitochondrial rich preparations was not significantly different in antiestrogen-treated (189.3 +/- 13.0) and untreated (225.0 +/- 15.1) animals. Collectively, these results suggest that the decline in placental P4 production observed in baboons in response to MER-25 occurs at least in part as a result of a decrease in cytochrome P-450scc activity. The loss in P-450scc activity appears to be an intramitochondrial event and not a result of depletion of the total mitochondrial cholesterol pool. We propose, therefore, that one mechanism by which estrogen may regulate the production of P4 by the placenta during primate pregnancy is via the maintenance of placental mitochondrial cytochrome P-450, the terminal oxidase of cytochrome P-450scc. PMID- 2924717 TI - Induction of ovarian cysts in progesterone-synchronized immature rats: evidence that suppression of follicular aromatase activity is not a prerequisite for the induction of cystic follicles. AB - Serum hormone profiles for women and animals with cystic ovaries have led to the hypothesis that elevated serum LH and androgens are involved in the induction of ovarian follicular cysts. To test the ability of LH-like activity to induce cysts, immature rats (bearing progesterone implants to suppress endogenous LH secretion) were assigned to treatment groups that received 0 (control), 0.1, 0.5, or 1.5 IU hCG twice daily for 9 days beginning on day 27 of life. Serum progesterone concentrations were maintained at approximately 156 ng/ml throughout the in vivo treatment period. By the morning of day 36 (day 10 of treatment) the largest follicles in ovaries from control animals were at the small antral stage of development. In contrast, the largest follicles in ovaries from rats receiving 0.1, 0.5, and 1.5 IU hCG were primarily at the large antral, precystic, and cystic stages of development, respectively. On all days tested, progesterone, androstenedione, and estradiol accumulation in medium alone was greater for follicles from rats receiving hCG than for follicles from control rats. Progesterone and androstenedione increased in response to cAMP in vitro in follicular incubations from both control and hCG-treated animals. Only estradiol production by follicles from rats treated with 0.1 or 0.5 IU hCG increased in response to cAMP in vitro. Follicles from all treatment groups produced significantly more estradiol in the presence of a saturating amount of aromatizable substrate than in medium alone. Indeed, on day 36, cystic follicles produced more than 8 ng estradiol when incubated in the presence of either androstenedione or testosterone. In addition, more androstenedione was accumulated in vitro when developing cysts were incubated with exogenous testosterone than when noncystic follicles were incubated under similar conditions. The results of these experiments demonstrate that chronic stimulation by LH-like activity is capable of inducing follicular cysts in a time- and dose related manner in intact noncycling immature rats. The ability of these cysts to produce 1-2 ng estradiol in medium alone and even greater amounts of estradiol in the presence of exogenous androgen indicates that inhibition of the ability of FSH to induce and stimulate follicular aromatase activity is not a prerequisite for the induction of follicular cysts in these animals. Finally, the increasing ability to accumulate androstenedione in the presence of exogenous testosterone suggests that follicular 17 beta-hydroxysteroid oxidoreductase activity increases in response to chronic stimulation by low doses of LH-like activity during the development of follicular cysts. PMID- 2924718 TI - Counterregulation of nuclear 3,5,3'-triiodo-L-thyronine (T3) binding by oxidized and reduced-nicotinamide adenine dinucleotide phosphates in the presence of cytosolic T3-binding protein in vitro. AB - The role of cytosolic T3-binding protein (CTBP) in the regulation of nuclear T3 binding was studied in vitro. Nuclear [125I]T3 binding was observed in the presence of 1.0 mM dithiothreitol (DTT). When the nuclei prepared from rat kidney were incubated with inactive form of CTBP which was also prepared from rat kidney, [125I]T3 binding to nuclei was not affected. When the nuclei were incubated with inactive form of CTBP in the presence of NADP, [125I]T3 binding to nuclei was increased, whereas binding was diminished when nuclei were incubated with CTBP in the presence of NADPH. The inactive form of CTBP was activated by NADPH. NADP also activated CTBP in the presence of DTT. Both active forms of CTBP were again inactivated by extraction with charcoal, and these inactive forms were reactivated by NADPH or by NADP and DTT, but not by NADP alone. Although the nuclei treated with 0.3 M NaCl lost the binding activity for [125I]T3 in the absence of NADP, the nuclei retained the binding activity for [125I]T3 in the presence of NADP and the inactive form of CTBP. Treatment of the nuclei with 0.5 M NaCl lost the binding activity for [125I]T3 not only in the absence but also in the presence of NADP and CTBP. These results suggested that NADP and NADPH play roles as counterregulatory factors for nuclear T3 binding in the presence of CTBP. Further, it was speculated that binding sites for the T3-CTBP complex, which is generated in the presence of NADP and DTT, are present in nuclei, and that binding sites for the complex are different from nuclear T3 receptors. PMID- 2924719 TI - Generation of osteoclastic function in mouse bone marrow cultures: multinuclearity and tartrate-resistant acid phosphatase are unreliable markers for osteoclastic differentiation. AB - The osteoclast is the cell that resorbs bone. It is known to derive from hemopoietic precursors, and a series of recent experiments has used enumeration of the tartrate-resistant acid phosphatase (TRAP)-positive multinucleate cells that develop in cultures of hemopoietic tissue as a means to analyze the regulation of osteoclast generation. These multinucleate cells have never been definitively characterized as osteoclasts, however, and we elected to assess the relationship among bone resorption (the primary function of the osteoclast), TRAP, and multinuclearity in mouse bone marrow cultures. Mouse bone marrow cells and peritoneal macrophages were incubated on plastic coverslips or bone slices for up to 14 days in the presence or absence of 1 alpha, 25-dihydroxyvitamin D3 [1 alpha,25-(OH)2D3]. Osteoclast generation, as judged by bone resorption, occurred in marrow cell cultures only in the presence of 1 alpha,25-(OH)2D3. However, TRAP-positive multinuclear cells developed both with and without the hormone. The multinuclear cells bound F4/80, a marker for macrophages that does not bind to osteoclasts. Peritoneal macrophages became multinucleate and developed TRAP positivity in culture to levels similar to those in freshly isolated osteoclasts, especially with 1 alpha,25-(OH)2D3, but remained nonresorptive. In cultures of marrow cells incubated with 1 alpha,25-(OH)2D3 bone resorption was more extensive than could readily be accounted for by the number of multinucleate cells present, and the size of excavations and extent of resorption suggested a major contribution by mononuclear cells with osteoclastic function. Thus, while TRAP and multinuclearity are reliable markers for osteoclastic phenotype in bone, they are unreliable markers in culture. Experiments designed to evaluate the regulation of osteoclast generation through enumeration of TRAP-positive multinucleate cells formed in bone marrow cultures will not only overstate, to an unknown and probably variable degree, the number of multinucleate osteoclasts that develop, but will also fail to even identify what may be a considerable and more substantial population of mononuclear cells that possess osteoclastic characteristics. PMID- 2924720 TI - Testosterone regulation of proopiomelanocortin messenger ribonucleic acid in the arcuate nucleus of the male rat. AB - GnRH regulates the secretion of LH and FSH, which stimulate the secretion of testicular hormones. Acting in a reciprocal fashion, these hormones, including testosterone and inhibin, exert a negative feedback effect on GnRH and gonadotropin secretion. Endogenous opioid peptides (EOPs) have been implicated to play a role in steroid-mediated regulation of gonadotropin secretion. In this context, certain steroid hormones (e.g. testosterone) increase EOP activity and ultimately inhibit GnRH secretion; however, the cellular mechanism by which this occurs is unknown. beta-Endorphin is one of these EOPs, and it is derived from a larger precursor molecule, POMC. We tested the hypothesis that testicular hormones and testosterone, in particular, stimulate POMC gene expression in the arcuate nucleus of the male rat brain. First, we compared POMC mRNA levels between intact and castrated male rats. Adult male rats were killed 4 days (n = 4) and 21 days (n = 5) after castration. Intact animals (sham-operated; n = 6) were used as controls. Using in situ hybridization and a computerized image analysis system, we measured the POMC mRNA content in individual cells of the arcuate nucleus. POMC mRNA signal was significantly lower (P less than 0.0003) in both 4-day (126 +/- 2 grains/cell) and 21-day (117 +/- 5 grains/cell) castrates than in controls (142 +/- 2 grains/cell). In a second experiment we tested whether testosterone would reverse the castration-induced loss of POMC message. Again, we castrated animals and immediately implanted them with either empty (sham; n = 6) or testosterone-containing Silastic implants (n = 5) of a size that would deliver physiological levels of testosterone (3.6 +/- 1.5 ng/ml). We observed that testosterone-treated animals had significantly higher levels of POMC mRNA signal (121.8 +/- 3.8 grains/cell) than sham-treated castrates (111.4 +/- 3.6 grains/cell; P less than 0.03) and that the testosterone-treated castrates had POMC mRNA signal levels indistinguishable from those of intact controls (122.0 +/- 1.1 grains/cell). These observations lend credence to the theory that one mechanism by which testosterone may regulate GnRH secretion is by increasing the synthesis of POMC in the arcuate nucleus. PMID- 2924721 TI - Regulation of prolactin synthesis in vitro by estrogenic and antiestrogenic derivatives of estradiol and estrone. AB - The estrogenic and antiestrogenic activities of derivatives of estradiol and estrone were determined in vitro using the ability of primary cultures of immature rat pituitary cells to synthesize PRL. Estradiol derivatives were the most potent estrogens in the assay. Large ethinyl substitutions in the 17 alpha position generally caused a decrease in estrogenic potency (up to 1000-fold). The 3 phenolic hydroxyl was important, but not essential, for the estrogenic activity of the estradiol molecule. Estratriene was approximately 1000 times less potent than estradiol. However, significant estrogenic activity was observed with the compound anordin (EC50, 8 x 10(-9) M), which could potentially be converted to a dihydroxylated derivative but without an aromatic A ring. Similarly, the steroid androst-5-ene-3,17-diol was weakly estrogenic (EC50, 3 x 10(-8) M). Steriods with a ketone in the A and D rings were generally inactive as estrogens and antiestrogens. Estradiol derivatives with 17 beta amines were only weak estrogens. Estrone derivatives were less active than the corresponding estradiol derivatives. 4-Nitromethoxyestrone exhibited weak antiestrogenic properties; however, 4-nitroestrone and methoxyestrone were both estrogens. The reason for the antiestrogenic properties of 4-nitromethoxyestrone is obscure, as the compound does not have structural features similar to those of known nonsteroidal antiestrogens. Minor alterations to the estradiol molecule at the 11 beta (OH) or 6 (ketone) position had little effect on estrogenic potency; however, large substitutions at the 11 beta (RU 39,411) or 7 alpha (ICI 164384) position produced antiestrogenic compounds. RU 39,411 was approximately 10 times more active as an antiestrogen than 4-hydroxytamoxifen, whereas ICI 164,384 was approximately 10 times less active than 4-hydroxytamoxifen. A series of hypothetical models is proposed that could explain the antiestrogenic properties of RU 39,411 and ICI 164,384 by an interaction with the estrogen receptor steroid binding site. PMID- 2924722 TI - Prostaglandins masculinize the mouse genital tract. AB - The masculinizing effects of prostaglandins (PGS) PGE2 and PGF2 alpha on mouse fetal genital tract differentiation were studied both in vivo and in vitro. Prenatal exposure to PGE2 and PGF2 alpha on days 11-17 of gestation (the critical period of the differentiation) increased the anogenital distance of the female fetuses in a dose-dependent manner. PGE2 also increased the anogenital distance of male fetuses in the presence of an inhibitor of testosterone synthesis, namely estradiol (2 mg/kg.day), and in the androgen-insensitive Tfmy males. Internally, PGE2 induced the epididymal duct in the females, estrogen-exposed males, and Tfmy males. However, no other changes were noticed in the internal genital tract of these fetuses. To avoid the problems associated with the placental transfer of any external agent, we also studied the effect of PGE2 in an in vitro system. Female genital ducts on day 13 of gestation were cultured in the presence and absence of different concentrations of PGE2 for a total of 6 days. PGE2 at doses 0.2 and 1 microgram/ml induced and stimulated the Wolffian and epididymal ducts. Thus, PGs appear to have a masculinizing role in androgen-induced sexual differentiation. PMID- 2924723 TI - Vagally mediated inhibition of acoustic stress-induced cortisol release by orally administered kappa-opioid substances in dogs. AB - The effects of oral vs. iv administration of kappa- and mu-opioid agonists on plasma cortisol release induced by acoustic stress (AS) were evaluated in fasted dogs with an implanted jugular catheter. AS was induced by 1 h of music (less than or equal to 86 decibels) played through earphones and was accompanied by a 382% maximal rise in plasma cortisol after 15-30 min. Administered orally 30 min before the AS session, both U-50488 (0.1 mg/kg) and PD 117-302 (0.05 mg/kg) significantly (P less than or equal to 0.01) decreased (by 71.2% and 80.9%, respectively) the maximal increase in plasma cortisol induced by AS, while bremazocine, morphine, as well as iv administration of U-50488 at similar doses were ineffective. The effects of U-50488 and PD 117-302 orally administered (0.1 mg/kg) on the hypercortisolemia induced by AS were abolished by pretreatment with iv naloxone (0.1 mg/kg) or MR 2266 (0.1 mg/kg). Naloxone given alone significantly (P less than 0.01) increased basal plasma cortisol, without affecting cortisol increase induced by AS. Vagotomy abolished the effects of orally administered U-50488 on the AS-induced increase in plasma cortisol. Neither U-50488 nor PD 117302 (0.1 mg/kg, orally) reduced the increase in plasma cortisol induced by intracerebroventricular administration of ovine CRF (100 ng/kg). It is concluded that kappa- but not mu-opioid agonists are able to inhibit the stimulation of the hypothalamo-pituitary-adrenocortical axis induced by AS by acting selectively on peripheral kappa-receptors located in the wall of the proximal gut. This action is neurally mediated through afferent vagal fibers affecting central nervous system release of CRF induced by a centrally acting stressor. PMID- 2924724 TI - Dilute estradiol implants and progestin receptor induction in the ventromedial nucleus of the hypothalamus: correlation with receptive behavior in female rats. AB - The ventromedial nucleus of the hypothalamus (VMN) is thought to constitute an essential neural substrate for hormonal induction of female sexual behavior. In previous work, implants of dilute (0.4%) estradiol (E2) have been found to prime progesterone-facilitated female sexual behavior in rats only when they are within or very close to the VMN. In other studies, induction of cytosolic progestin receptors (PRc) in the hypothalamus has been correlated with systemic E2 priming of receptive behavior. We combined dilute E2 implants with a Palkovits punch microassay for PRc in the an effort to examine the relationship between estrous behavior and estrogen-induced PRc in the VMN of individual female rats. Ovariectomized rats were given bilateral guide cannulae aimed at the VMN and were primed for 3 days with 1) blank implants plus oil sc, 2) blank implants plus 0.5 micrograms E2 benzoate sc, 3) implants of 0.4% E2 in cholesterol, or 4) implants of 2.0% E2. On day 4 all rats received progesterone (P) sc and were tested for receptive behavior. The following week all subjects received the same estrogen priming treatment but were killed on day 4 without P treatment. The VMN was punch dissected and assayed for PRc. High levels of lordosis were seen in the E2 benzoate-treated and 2.0% E2-implanted animals, while little behavior was seen in the oil-treated animals. Among 0.4% E2-implanted animals, higher levels of lordosis were observed in subjects with implant placements in the rostral than in the caudal VMN; however, lordosis quotients were not correlated with PRc induction measured in the entire VMN of individual animals. In general, our findings suggest that local estrogenic stimulation of target cells in the VMN is capable of both priming the estrous response and induction of P receptors. Whether these two effects are causally related awaits future study. PMID- 2924725 TI - Abnormal properties of thyroglobulin in mice with inherited congenital goiter (cog/cog). AB - A recessive autosomal mutation (cog) in mice that results in congenital goiter was recently described. Since the mutation has been linked to the thyroglobulin (TG) gene, we have studied the immunological and physical properties of TG in cog/cog mice. +/Cog mice, which are phenotypically normal, were used as controls. In a mouse TG RIA the displacement curve produced by cog/cog thyroid extract was not parallel to normal murine TG, and at maximum displacement 15.4% of the tracer was still bound to the antibody. Extract from +/cog thyroid tissue produced parallel and complete displacement. Sucrose density gradient velocity centrifugation followed by RIA was used to determine the sedimentation properties of cog/cog TG. An abnormal pattern was obtained; a small peak in the 3-8S area and a broad, poorly defined peak at 12S and extending to above 27S were present. By comparison, +/cog thyroids had sharp peaks at 19S and 27S. These findings suggest that normal TG contains some immunological determinants that are absent, and some that are altered, in cog/cog TG. They also indicate that the association of 12S subunits to form 19S TG in cog/cog mice is weak and abnormal. Thyroid tissue was labeled with Na125I in vivo and with [35S] methionine in vitro. In cog/cog mice iodine was incorporated predominantly into albumin and other non-TG proteins. However, by polyacrylamide gradient gel electrophoresis, distinct 125I labeled bands comigrating with normal TG were present. The bands migrating with TG were also precipitable with anti-TG antiserum. In +/cog mice TG was the predominant iodinated molecule. With [35S]methionine labeling, cog/cog and +/cog thyroids formed TG with the same electrophoretic mobilities. These data indicate the cog/cog thyroids synthesize TG of normal, or very nearly normal, size. The immunological and sedimentation properties of this TG are abnormal, supporting the possibility that the cog mutation is in the TG gene. PMID- 2924726 TI - The effects of platelet-derived growth factor in cultured microvessel endothelial cells. AB - The effects of platelet-derived growth factor (PDGF) on thymidine incorporation into DNA and glucose and neutral amino acid uptake were studied in endothelial cells cultured from macrovessels (bovine aorta and pulmonary artery) and microvessels (bovine fat and mouse brain). Similar to previous studies, PDGF did not bind to macrovessel cells, nor did it influence their metabolic function. In contrast, PDGF bound specifically to the two types of microvessel cell culture and in these cells also stimulated the uptake of glucose and neutral amino acids as well as the incorporation of thymidine into DNA. Stimulatory effects of PDGF occurred at concentrations of 2 ng/ml, with maximal stimulation up to 5-fold of the control value for amino isobutyric acid and glucose uptake and up to 8- to 10 fold for thymidine incorporation. The maximal effects of PDGF were additive to those of insulin-like growth factor, I, a known stimulator of all three metabolic processes in microvessel endothelial cells. The binding of PDGF to the endothelial cells was, in general, equivalent to PDGF binding to human foreskin fibroblasts, both in the magnitude of tracer binding and in the affinity of binding. Similar effects were found with recombinant and platelet-derived PDGF. We conclude that these two cultured microvessel endothelial cells not only produce PDGF-like material, but are capable of binding and responding to PDGF. PMID- 2924727 TI - Cholesterol flux between high density lipoproteins and cultured rat luteal cells. AB - Although high density lipoprotein (HDL) is a promoter of cholesterol efflux from peripheral cells, in steroidogenic tissues it has been shown to provide cholesterol for steroid synthesis. The present study examines the dynamics of cholesterol exchange between HDL particles and rat luteal cells. Cholesterol influx was measured by following the uptake of label from HDL particles labeled with [3H]cholesterol or [3H]cholesteryl linoleate. The efflux of cholesterol was simultaneously measured by incubating [3H]cholesterol-labeled luteal cells with unlabeled HDL. Conversion of endogenous and lipoprotein-derived steroids to progestins was also determined. The results showed that HDL promotes both influx and efflux of cholesterol in those cells. The amount of influx exceeds efflux, thus resulting in a net uptake of cholesterol from HDL by rat luteal cells. The relative utilization of endogenous vs. HDL-derived cholesterol for steroid synthesis was also examined. The results show that only a fraction of the HDL derived cholesterol was converted directly to steroids. The fraction that was converted depended on the HDL concentration and had no apparent relation to the incubation time. These results show that although cholesterol flux in luteal cells is bidirectional in the presence of HDL, the influx exceeds the amount of efflux, and the internalized cholesterol is diluted with the endogenous cholesterol pool before it is converted to steroids. PMID- 2924728 TI - Two-dimensional gel autoradiographic analysis of the acute effects of estradiol on protein synthesis in the female rat ventromedial nucleus in vivo. AB - Estradiol (E2) alters protein synthetic events in the ventromedial nucleus (VMN) of the hypothalamus to promote lordotic behavior in the female rat. This study analyzed the acute changes induced by E2 in proteins synthesized in the VMN in vivo as measured by 35S incorporation into protein, two-dimensional gel electrophoresis, autoradiography, and computerized optical densitometry. Ovariectomized rats received vehicle or E2, Hamilton syringes were placed stereotaxically in the VMN bilaterally, and 0.9 mCi 35S-labeled methionine and cysteine was infused over 1 h. After 6 h, rats were killed, and VMN samples were subjected to isoelectric focusing and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Resultant gels underwent autoradiography, and the optical density of each of 240 spots was quantitated using a flat-bed laser scanner. Using a quantitation algorithm based on the linearity and reproducibility of the scanner and film, 123 spots were analyzed for changes in optical density and relative mol wt (MW) and isoelectric point (pI) induced by E2. The spot induced most prominently by E2 had a MW of 70K and a pI of 6.0, confirming previous results. Three spots were quantitatively induced by E2: 1) a 47K MW, pI 5.4 phosphoprotein (96% induction); 2) a 45K MW, pI 5.2 protein (72% induction); and 3) a 100K MW, pI 5.5 protein (82% induction). Two spots increased pI with E2: 1) a 110K MW protein increased from pI 5.4 to 5.5; and 2) a 50K MW protein increased from pI 6.3 to 6.4. Under these conditions and using a quantitative algorithm, only a small number of proteins synthesized in the VMN were induced by E2 in vivo. E2 also exerts effects on the posttranslational modification of another select group of proteins. These proteins may subserve at least part of the physiological effect of E2 in the VMN. PMID- 2924729 TI - Regulation of the glucose transporter in developing rat brain. AB - We have found a complex alteration in the expression of the glucose transporter protein and mRNA in developing rat brain tissue. Before birth (gestational days 19-20), the rat brain glucose transporter was comprised of a diffuse protein doublet of approximately 43,000 and 50,000 mol wt (Mr) by Western blot analysis. Immediately after birth (1-2 days), the total amount of immunoreactive glucose transporter decreased approximately 5-fold, primarily due to a loss of the higher (50,000) Mr component with a relatively smaller decrease in the 43,000 Mr band. Subsequently, the amount of the 43,000 Mr band progressively increased from days 5 to 60 and the 50,000 Mr band increased from days 15 to 60. By 60 days postdelivery, the relative amounts of the glucose transporter protein were similar to those on the 19th gestational day. N-Glycanase treatment of the developing rat brain membranes demonstrated that the regulation of the two different Mr weight glucose transporter species occurred as a result of differential glycosylation. In contrast to the Western blot analysis, [3H] cytochalasin-B binding studies demonstrated no significant developmental alteration in the total amount of glucose transporter protein in rat brain tissue. However, consistent with the Western blots, Northern blot analysis using rat brain transporter cDNA revealed a dramatic decrease in the content of the glucose transporter mRNA immediately subsequent to birth, followed by a gradual increase back to the prenatal levels. These data suggest that the rat brain-type glucose transporter is developmentally regulated, but may be associated with the compensatory expression of another unidentified glucose transporter protein in newborn rats. PMID- 2924730 TI - Molecular identification and characterization of the gastrin receptor in guinea pig gastric glands. AB - The binding characteristics of 125I-labeled Leu15-gastrin and the molecular identification of the gastrin receptor was investigated in dispersed guinea pig gastric glands. The binding of [125I]gastrin to gastric glands was temperature dependent, saturable, and specific. At 37 C, the binding was rapid, became maximal within 10 min, and declined after 30 min; at 24 C, binding reached a steady state between 30 and 60 min. The dissociation of specifically bound gastrin was also rapid, with 35% of the radioligand dissociating in 5 min at 37 C. Gastrin displaced [125I]gastrin in a dose-dependent manner, with 50% displacement at 4.4 nM. Scatchard analysis of the saturation curve was best described by a one-site binding model with a Kd of 2.3 nM and maximum binding of 6.0 x 10(-10) M/mg DNA. A significant reduction of [125I]gastrin binding to glands occurred in the presence of GTP (0.1 mM), (Bu)2-cGMP (1.0 mM), and protease inhibitors. Chemical cross-linking studies using the cross-linking reagent disuccinimidyl suberate and sodium dodecyl sulfate-gel electrophoresis identified a major band with a mol wt of 78K and several other lower mol wt bands in the range of 60K, 48K, and 38K. Identical electrophoretic patterns were obtained when glands were bound and solubilized in the presence and absence of dithiothreitol, showing the lack of disulfide bonds in the gastrin receptor subunit structure. Since dithiothreitol significantly enhanced radioligand binding when present during binding, its observed actions are most likely in the intracellular processing of the radioligand and not at the receptor level. PMID- 2924731 TI - Enhanced dopamine synthesis and release in vitro in the median eminence of rat hypothalamus are associated with involution of estradiol-induced pituitary tumors. AB - Changes in the functions of tuberoinfundibular dopaminergic (TIDA) neurons were investigated during the period when the involution of estradiol-induced PRL secreting pituitary tumors was occurring. Dopamine synthesis and release in vitro by TIDA neurons were determined by 3,4-dihydroxyphenylalanine (DOPA) accumulation in the median eminence and endogenous dopamine release from the median eminence, respectively. Three weeks after a single injection of 2 mg estradiol valerate into ovariectomized rats, there was a marked increase in the weight of anterior pituitaries and the concentration of serum PRL, but a decrease in K+-induced DOPA accumulation in vitro in the median eminence. Twelve weeks after estradiol treatment, by which time pituitary weights and PRL concentrations declined considerably, K+-induced DOPA accumulation in the median eminence rose 5-fold compared to that in control animals. This change in DOPA accumulation persisted for 24 weeks. Increases were observed at 12 weeks in K+-induced as well as basal and (Bu)2cAMP-induced DOPA accumulation in the median eminence. The increases in basal and (Bu2cAMP-induced DOPA accumulation were not altered by Ca2+ removal from medium. In parallel to the changes in DOPA accumulation, basal and K+ induced release in vitro of dopamine from the median eminence into the medium were decreased 3 weeks after estradiol treatment, but increased at 12 and, in part, 24 weeks. The increases in basal and K+-induced dopamine release were observed even after Ca2+ removal from medium. These results suggest that basal, extracellular Ca2+-dependent, and cAMP-dependent dopamine synthesis as well as basal and depolarization-induced dopamine release in TIDA neurons are stimulated during the period of involution of pituitary tumors associated with estradiol withdrawal. PMID- 2924732 TI - Adenosine triphosphate activates the phospholipase-C cascade system in human amnion cells without increasing prostaglandin production. AB - Human amnion is hypothesized to be a target tissue for hormone messages from the fetus regarding labor. We have previously demonstrated prostaglandin E2 (PGE2) release in amnion after treatment with phorbol and oxytocin, but other potential agonists of the inositol phospholipid/protein kinase-C system have not been investigated. The effects of extracellular ATP on cytosolic calcium concentration [( Ca2+])i) inositol phosphate (IP) accumulation, and PGE2 production were studied in cultured human amnion cells. Intracellular free calcium [Ca2+]i was measured using the fluorescent dye fura-2. Addition of 0.01-30 microM ATP resulted in a [Ca2+]i transient which peaked within 15 sec and returned to baseline over 10 min. UTP (1 microM) was more effective than ATP (1 microM); [Ca2+]i levels rose from 233 to 2880 nM (UTP) and 2320 nM (ATP). A reduced effect was observed with other nucleotides in a rank order of agonist potency of ITP greater than CTP greater than ADP greater than GTP greater than TTP. No effect was seen with AMP, cAMP, or adenosine. This is consistent with P2 purinoceptors, as described in other tissues. ATP (100 microM) also dramatically increased IP accumulation. Inositol triphosphate, inositol bisphosphate, and inositol monophosphate were increased 7-, 9-, and 16-fold respectively. The agonist potency order of other nucleotides for IP accumulation was the same as that of [Ca2+]i. Pharmacological concentrations of ATP (1 mM) were required to increase PGE2 production. Many other nucleotides were equally effective at this concentration. ATP activates the phospholipase-C system in human amnion, as demonstrated by the increase in [Ca2+]i and inositol phosphates. The physiological significance of purinergic stimulation of this tissue remains unclear. PMID- 2924733 TI - Identification of immunoreactive neuropeptide-gamma in human placenta: localization, secretion, and binding sites. AB - The aim of the present study was to evaluate the possible presence of immunoreactive neuropeptide-gamma (irNPY) in human placenta. Acidic extracts of human placental tissue collected at term pregnancy contained high irNPY concentrations. The extracted irNPY eluted from HPLC with the same retention time as synthetic NPY. The presence of the peptide in placental cells was confirmed by immunohistochemical findings showing numerous cells of the cytotrophoblast layer positively staining for NPY. Further supporting local production of the peptide, primary cultures of human placental cells released irNPY into the culture medium and the addition of high K+ concentrations increased the release of the peptide. The finding of irNPY in human placenta stimulated the characterization of binding sites of NPY in the same tissue. Using autoradiographic techniques we showed specific binding of [125I]NPY in human placental tissue. The binding of [125I]NPY to the placental receptors was saturable and widely distributed within the placental tissue. Finally, the addition of NPY to the medium of cultured placental cells increased the release of immunoreactive CRF, suggesting a possible role of NPY in placental hormone production. The effect of NPY was dose related and augmented by the addition of norepinephrine (10 nM). These results showed that human placenta produces and secretes irNPY and that NPY receptors are present in placental tissue. Moreover, the evidence that NPY stimulated the release of immunoreactive CRF from cultured placental cells suggests an action of NPY in placental hormonogenesis. PMID- 2924734 TI - Prolactin messenger ribonucleic acid concentrations in 4-day cycling rats and during the prolactin surge. AB - Pituitary PRL mRNA concentrations were measured during the 4-day rat estrous cycle. Adult female Sprague-Dawley rats were killed at 3-h intervals throughout the cycle and hourly between 1000 and 2400 h on proestrus (n = 5-12). Serum PRL was increased on the afternoons of proestrus (P) and estrus (E), with peak concentrations at 1700 h (P, 624 +/- 126; E, 261 +/- 107 ng/ml). PRL mRNA concentrations were elevated during the evening on P and E (2300 h: P, 14.4 +/- 1.5; E, 16.1 +/- 1.3 ng cDNA bound/100 micrograms pituitary DNA) to values 2-fold higher than those at 0800 h on each respective day. On diestrus (D) PRL mRNA levels decreased abruptly during the morning (1100 h, 1.7 +/- 0.3 ng cDNA bound), followed by a 6- to 7-fold increase between 1700 and 2000 h on the same evening. In contrast, PRL mRNA levels were elevated at 0800 h on metestrus (M). The changes in PRL mRNA concentrations obtained on M and D were not associated with increased PRL secretion. A more detailed examination of P revealed that PRL mRNA levels increased during the morning (1000 h, 9.9 +/- 2.6 ng cDNA bound), then decreased abruptly at 1100 h (4.9 +/- 1.2). The morning rise in mRNA concentrations was followed by a 2-fold rise in pituitary PRL content. As serum PRL rose during the afternoon surge, a coincident decrease in pituitary PRL content and an increase in PRL mRNA levels were observed. The relationship between PRL secretion and gene expression was further examined in ovariectomized estradiol-replaced rats receiving either bromocriptine (1.2 mg/day, sc) or vehicle control sc. The vehicle-treated group expressed a characteristic afternoon PRL surge between 1500 and 2100 h. Pituitary PRL decreased during the surge to 10% of morning values, and PRL mRNA levels increased 2-fold beginning 2 h after initiation of the surge. These changes in serum PRL, pituitary PRL, and PRL mRNA levels were abolished by bromocriptine administration. These data reveal that alterations in PRL mRNA concentrations occur on a daily basis during the rat estrous cycle. Increases occur during the evenings of P and E at the time of the increase in PRL secretory activity. The effect of blocking the PRL surge in ovariectomized estradiol-replaced rats suggests a regulatory interaction between secretion and gene expression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2924735 TI - A molecular dynamics study of the C-terminal fragment of the L7/L12 ribosomal protein. II. Effects of intermolecular interactions on structure and dynamics. AB - The crystallographic dimer of the C-terminal fragment (CTF) of the L7/L12 ribosomal protein has been subjected to molecular dynamics (MD) simulations. A 90 picosecond (ps) trajectory for the protein dimer, 19 water molecules and two counter ions has been calculated at constant temperature. Effects of intermolecular interactions on the structure and dynamics have been studied. The exact crystallographic symmetry is lost and the atomic fluctuations differ from one monomer to the other. The average MD structure is more stable than the X-ray one, as judged by accessible surface area and energy calculations. Crystal (non dimeric) interactions have been simulated in another 40 ps trajectory by using harmonic restraints to represent intermolecular hydrogen bonds. The conformational changes with respect to the X-ray structure are then virtually suppressed. The unrestrained dimer trajectory has been scanned for cooperative motions involving secondary structure elements. The intrinsic collective motions of the monomer are transmitted via intermolecular contacts to the dimer structure. The existence of a stable dimeric form of CTF, resembling the crystallographic one, has been documented. At the cost of fairly small energy expenditure the dimer has considerable conformational flexibility. This flexibility may endow the dimer with some functional potential as an energy transducer. PMID- 2924736 TI - Periodic electric field as a biopolymer conformation switch: a possible mechanism. AB - A theoretical model is proposed to describe the influence of a periodic electric field (PEF) upon a biopolymer. The biopolymer is treated as a classical mechanical system consisting of subsystems (molecular groups) which interact with each other through potential forces. The PEF is treated as a periodic driving force applied to a molecular group. The energy dissipation is considered using the model of fluid (viscous) friction. Arguments for the non-linear character of the friction-velocity dependence caused by the non-Newtonian rheology of a viscous medium are formulated. A forced molecular-group motion is investigated for the situation of a small driving-force period, with oscillations overdamped and a driving force consisting of more than one harmonic. As a result, it is established that the motion always gets to a terminal stage when only a small scale vibration about some point, X*, takes place. The terminal motion is preceded by a transient characterized by the presence of a directional velocity component and so by a drift along a potential profile. The drift goes on until a barrier is met which has a sufficiently large steepness (the barrier height is not important). As a result, the point X* may happen to be remote from the conformation potential local minimum (conformational state). The physical reasons for the drift are described.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2924737 TI - The dynamic properties of melittin in solution. Investigations by NMR and molecular dynamics. AB - Molecular dynamics simulations are described for the peptide melittin. The atomic trajectories are calculated both with normal potential energy functions and with additional distance restraints deduced from nuclear Overhauser effects observed in NMR experiments. The results are compared with NMR data on coupling constants and amide exchange rates and with B-factors from X-ray crystallography. The observed correlations between experiment and molecular dynamics simulations suggest a relatively mobile C-terminus and relatively high flexibility around residue 11. It is noted that the high conformational variation around residue 11 is due in part to the presence of a proline at position 14 which results in a "missing" H-bond in the largely alpha-helical structure. It is also noted that a proline is a common feature of many putative membrane spanning helices. A role for such prolines is suggested. PMID- 2924738 TI - Can hydration forces induce lateral phase separations in lamellar phases? AB - Large repulsive forces measured between membranes of lamellar lipid phases at low hydration are attributed to hydration interactions which vary widely among lipid species. We include this interaction in a model of lamellar phases of two membrane components (two lipids or lipid and protein). The surface polarization of a mixture is taken as a linear combination of those of the components. The model predicts phase separation at low hydration. This may have important consequences for living cells which are dehydrated either by the osmotic effects of tissue freezing, or by desiccation in unsaturated atmospheres. PMID- 2924739 TI - Fractal scaling mechanisms in biomembranes. Oscillations in the lateral diffusion coefficient. AB - A modified model of the Cohen-Turnbull free volume theory for lateral transport processes in biomembranes is presented. The model which is based on renormalization group theoretical concepts incorporates fractal rather than Markovian diffusion kinetics. It predicts harmonic oscillations in the lateral diffusion coefficient around a dominant power-law trend and clarifies, in addition, recently observed deviations from the Cohen-Turnbull exponential law. PMID- 2924740 TI - Basal temporal subdural electrodes in the evaluation of patients with intractable epilepsy. AB - In evaluation of patients with complex partial seizures who are candidates for surgical treatment, exact definition of the epileptogenic focus is essential for a good surgical outcome. We report a new technique which permits detailed mapping of the epileptogenic activity in the basal temporal lobe and the convexity of the temporal lobe. The technique consists of placement of at least 16 basal temporal electrodes and an additional 64 electrodes covering the temporal convexity. This extensive coverage permits accurate definition of the limits of the epileptogenic focus and also of adjacent functional areas and therefore allows more significant determination than have previous techniques of the ideal extent of the surgical resection. This accuracy cannot be achieved with depth electrodes or the limited coverage provided by previously reported epidural or subdural electrode techniques. PMID- 2924741 TI - Quantitative comparison of cell loss and thiopental-induced EEG changes in human epileptic hippocampus. AB - Thiopental-induced EEG beta activity recorded from mesial and lateral temporal lobe sites was analyzed both visually and by computer in 30 patients with complex partial seizures. All patients later received anterior temporal lobectomy. Volumetric cell densities and percentage of principal cell loss relative to normal controls were determined in several different areas of each resected temporal lobe. The percentage of drug-induced beta activity was then compared with the percentage of cell loss by (a) making precise topographic correlations between induced beta and cell loss, (b) relating the overall degree of left/right beta asymmetry to cell loss averaged over wide regions, and (c) comparing the likelihood of left/right beta asymmetries in patients with and without extreme cell loss. The results obtained were consistently negative and were unaffected by whether EEG data were analyzed by computer or visual inspection. These results indicate that the well-known loss of drug-induced beta activity found in epileptogenic regions is not an indicator of the degree of cell loss or sclerosis. The underlying focal dysfunction measured by EEG beta activity remains unknown, and factors such as focal hypoperfusion, hypometabolism, and the microanatomic features of the cells remaining in the focus should be investigated. PMID- 2924742 TI - Seizure frequency and major life events in epilepsy. AB - A group of 18 patients with chronic epilepsy were followed in an outpatient clinic for 1-6 years. Month-by-month seizure records were kept and the response to treatment was systematically explored. The present study was prompted when three patients became seizure-free, apparently in response to major life events (marriage, parenthood, and retirement) rather than to changes in treatment. All the subjects were interviewed in their own homes with a companion, friend, or relative present. The interview was based on a standard instrument (Life Experiences Survey, LES). The home environment was chosen to facilitate recall of events and to enable subjects to confirm dates. The seizure record was then compared with the parallel life events record. Two methods of analysis were adopted. In the first, each life event was assumed to have impact on seizure frequency only during the month in which it occurred; life event months were compared with non-life-event months. In the second, a life event was considered a watershed; seizure frequencies before and after the event were compared. Nonparametric statistical methods were used. These approaches revealed associations between life events and seizure frequency in three additional patients (total six). Most of the patients who showed an association experienced partial seizures. PMID- 2924743 TI - Seizures and seizure care in an emergency department. AB - We evaluated the nature and significance of seizure problems in an emergency department (ED) by studying seizures in an urban community hospital. In 6 months, there were 29,131 ED visits; of these, 200 (0.7%) were for diagnosed seizures. Among these 200 seizure visits, were 69 (34.5%) new-onset seizures, 30 (15%) febrile seizures, and 92 (46%) seizures in epilepsy patients with prescribed antiepileptic drugs (AEDs). These seizures were often serious and complicated by medical and psychosocial problems; e.g., 37 patients (18.5%) had multiple seizures, 14 (7%) had status epilepticus, and 63 (31.5%) required hospitalization. Associated psychosocial problems included 61 patients (31%) who had no medical insurance, 62 others (31%) who were judged indigent, and 60 (30%) who abused alcohol. Of 92 epilepsy patients receiving AEDs, 52 (56.5%) had subtherapeutic blood levels and were noncompliant with AED prescription patients. Problems with continuity of care were demonstrated by the failure of the ED to communicate with primary care providers about drug levels, noncompliance, and changes in therapy in greater than 85% of patients. A hospital ED is a major source for epilepsy and seizure care, but this care is not always optimum. EDs need to be prepared to manage common acute seizure problems. However, EDs must also place greater emphasis on significant nonemergency aspects of seizure care such as AED compliance, associated psychosocial problems, and effective communication with primary care providers. PMID- 2924744 TI - Electrophysiologic effects of gamma-vinyl GABA and carbamazepine. AB - The effects of gamma-vinyl GABA (GVG) and carbamazepine (CBZ) monotherapy on somatosensory (SEP) and visual (VEP) evoked potentials and spectral quantitative EEG (QEEG) were studied in 17 patients with complex partial seizures using a cross-over double-blind study design. CBZ was associated with statistically significant prolongation of SEP latencies. When the drug was switched to GVG, shortening of the peak latencies was observed. Prolonged pattern-VEP peaks were observed both during CBZ and GVG monotherapies. A similar but more subtle tendency of the peaks was observed in P100 latencies. Spectral EEG revealed a slowing of the occipital rhythm with CBZ. No QEEG changes related to GVG were found. The use of multimodal evoked potentials and QEEG should be considered in studying the effects of new antiepileptic drugs (AEDs). PMID- 2924745 TI - Effect of naloxone infusion on the rate of epileptiform discharges in patients with complex partial seizures. AB - In experimental studies, endogenous opioids have shown protective effects on seizure recurrence and facilitatory effects on postictal inhibition that were reversed by the opioid antagonist, naloxone. We evaluated the effect of all-night continuous infusion of 10 mg naloxone on the rate of focal interictal epileptiform discharges (FIEDs) during sleep in eight men with complex partial seizures (CPS) during 2 consecutive nights. Patients with abundant FIEDs during the control night showed a mean increase of 39% in the rate of FIEDs per unit of time during the naloxone infusion night. During the naloxone infusion night, mean nocturnal plasma prolactin (PRL) concentrations in this group of patients showed significant elevation, which was correlated with increased density of FIEDs. All night infusion of naloxone failed to show any effect on the remaining three patients with minimal or no FIEDs during the control night. Mean nocturnal plasma PRL concentrations in this group of patients was significantly lower than in the former group. Our data support the notion that, in response to interictal or ictal discharges, endogenous opioid peptides may exert an inhibitory action that is reversible by administration of naloxone. PMID- 2924746 TI - Chronic carbamazepine treatment in the rat: efficacy, toxicity, and effect on plasma and tissue folate concentrations. AB - Folate depletion has often been a problem in chronic antiepileptic drug (AED) therapy. Carbamazepine (CBZ), a commonly used AED, has been implicated in some clinical studies. A rat model was developed to examine the effects of chronic CBZ treatment on folate concentrations in the rat. In the course of developing this model, a common vehicle, propylene glycol, by itself in high doses, was found to exhibit protective properties against induced seizures and inhibited weight gain. Seizures induced by hexafluorodiethyl ether (HFDE) were also found to be a more sensitive measure of protection by CBZ than seizures induced by maximal electroshock (MES). Oral administration of CBZ as an aqueous suspension every 8 h at a dose of 250 mg/kg was continuously protective against HFDE-induced seizures and was minimally toxic as measured by weight gain over 8 weeks of treatment. The CBZ levels measured in plasma and brain of these animals, however, were below those normally considered protective. This treatment with CBZ had no apparent adverse effect on folate concentrations in the rat, and, indeed, the folate concentration increased in liver after 6 weeks of treatment and in plasma at 8 weeks of treatment. PMID- 2924747 TI - Phenytoin-induced seizures: a paradoxical effect at toxic concentrations in epileptic patients. AB - We examined the incompletely defined convulsant action of phenytoin (PHT) at toxic concentrations in humans. A retrospective chart review (1979-1985) yielded 96 cases (90 patients), meeting both clinical and laboratory criteria for PHT intoxication. Seven patients, all with epilepsy, had one or more seizures while toxic. However, in only two patients (2.1%) with serum concentrations of 93.2 and 69.7 micrograms/ml was a causal relationship deemed highly probable. Seizures did not occur in most toxic epileptic patients with total serum PHT concentrations as high as 85.1 micrograms/ml or in any of the nonepileptic patients with concentrations as high as 64.2 micrograms/ml. The lack of convulsant action of PHT in these patients suggests that seizure risk may be multifactorial and also that PHT is a weak convulsant. We conclude that PHT at very high concentrations can rarely exacerbate seizures or even precipitate generalized status in some epileptic patients, a paradoxical effect. PMID- 2924748 TI - Brain interstitial fluid and intracellular distribution of phenytoin. AB - After intravenous (i.v.) administration (10 mg/kg), the biodisposition of phenytoin (PHT) in serum (total and free concentration), cerebrospinal fluid (CSF), brain, and the interstitial fluid (IF) of the normal brain were determined in dogs. A sufficient volume of IF was obtained through a multiperforated polypropylene ball implanted into the left parietotemporal region for 4-5 weeks. PHT brain distribution coefficient values ranged between 1.9 and 3.75, while the ratios of IF to free serum PHT concentrations ranged between 0.19 and 1.04; thus, our data indicate that most of the free unbound PHT which enters the brain parenchyma accumulates in the cellular compartment. Furthermore, at 60 and 90 min the peak CSF and IF concentrations are delayed; thus, for PHT, an apparent diffusion front from the CSF into the extracellular space of the brain seems to occur. PMID- 2924749 TI - Lack of sister chromatid exchange induction in phenytoin-treated patients with epilepsy. AB - Phenytoin (PHT) has been suspected of having a mutagenic effect with chronic administration, but the existing evidence is equivocal. Contradictory results have been obtained using different testing systems. Sister chromatid exchange (SCE), a sensitive indicator of genotoxic environmental influences, has been used in only a few limited studies of PHT users, with varying results. The present study was designed to evaluate the potential mutagenicity of PHT in a more objective and reliable way than has been done previously. Following careful screening procedures, 16 adult male patients with epilepsy receiving long-term PHT monotherapy and 16 healthy controls were selected for a study of SCE frequencies in peripheral lymphocytes. The patients and controls were matched for sex, age, and smoking habits. Strict exclusionary criteria were observed, including all factors known to affect or suspected of affecting the SCE frequencies. Statistical analyses did not reveal any significant differences between the SCE rates of PHT-treated patients and controls, indicating a lack of PHT mutagenicity as expressed by induction of SCE in adults. PMID- 2924751 TI - Monograph on regulation of differentiation in eukaryotic cell systems. PMID- 2924750 TI - Reduction of the teratogenic effects of phenytoin by folic acid and a mixture of folic acid, vitamins, and amino acids: a preliminary trial. AB - Four groups of pregnant rats were used to study the effects of dietary supplements of folic acid (FA) alone or a mixture of FA, vitamins (Vit), and amino acids (AA) on the teratogenic effects of phenytoin (PHT). Groups A, B, and C received intraperitoneal (i.p.) injections of high-dose (75 mg/kg/day) phenytoin (PHT) between 9 and 11 days of gestation, while the controls, group D, rats received distilled water. The diet was modified in groups A and B. Group A received a mixture of FA, Vit, and AA, while group B received FA supplementation alone. Groups C and D received a regular diet. We found that PHT, when administered without dietary supplementation, resulted in a decrease in weight and length of the fetuses, an increased rate of subcutaneous (s.c.) bleeding, a retardation of ossification centers, and an increased number of malformations. Supplementation of the diet with FA alone or FA with Vit and AA resulted in statistically greater fetal weight and length, decreased subcutaneous bleeding, more ossification centers, and fewer malformations. The mixture of FA and Vit and AA was superior to FA alone in reducing the incidence of internal abnormalities, ossification abnormalities of the distant phalanxes, and s.c. bleeding. PMID- 2924754 TI - Cytogenetic investigations of human subjects occupationally exposed to chemicals from the petroleum-processing industry. AB - A cytogenetic investigation was carried out of 55 workers from the petroleum processing industry and of 30 control subjects. The frequencies of both structural and numerical chromosome aberrations and of sister chromatid exchanges were determined simultaneously and the relationship among these cytogenic indices were analyzed. The incidence of chromosome aberrations and sister chromatid exchanges among the petroleum workers was higher than that among the controls. The cytogenic indices demonstrated a clear dependence on the working environment of the subjects and a correlation with the existence of some reproductive failures in the families of the exposed workers. Our results indicate the presence of some mutagenic risk in the working environment of some of the divisions in the petroleum-processing industry due to the genotoxic influence on the somatic cells of the exposed workers at a cytogenetic level. This potential risk is mainly associated with the presence of some heavy oil-fractions and polycyclic aromatic hydrocarbons in the working environment. PMID- 2924752 TI - Mechanisms of asbestos-induced squamous metaplasia in tracheobronchial epithelial cells. AB - Within 1 to 4 weeks after exposure to asbestos, differentiated rodent and human tracheobronchial epithelial cells in organ culture undergo squamous metaplasia, a putative preneoplastic lesion characterized by conversion of mucociliary cell types to keratinizing cells. The exogenous addition of retinal acetate (RA) to culture medium of hamster tracheal organ cultures reverses preestablished, asbestos-induced squamous metaplasia, although data suggest that the effectiveness of RA decreases as the length of time between exposure to asbestos and initial application of RA increases. alpha-Difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC), inhibits squamous metaplasia caused by asbestos or vitamin A deficiency, whereas addition of methylglyoxal bis(guanylhydrazone) (MGBG), a structural analog of spermidine and inhibitor of S-adenosylmethionine decarboxylase, causes an enhancement of metaplasia under both circumstances. Basal cell hyperplasia and increased incorporation of 3H-thymidine by tracheal epithelial cells also are seen after addition of the polyamines, putrescine or spermidine, to tracheal organ cultures, an observation supporting the importance of polyamines in the development of this lesion. The use of retinoids and inhibitors of ODC could be promising as preventive and/or therapeutic approaches for individuals at high risk for development of asbestos-associated diseases. PMID- 2924753 TI - Control of differentiation in BC3H1 muscle cells. AB - BC3H1 is a cell line that undergoes a musclelike pattern of differentiation under the appropriate conditions. We have examined the control of the synthesis of proteins characteristic of differentiated muscle in these cells as a function of their position in the cell cycle. We define two positions in the cell cycle where BC3H1 cells can remain stably quiescent. G1d is a restriction point early in the G1 portion of the cell cycle that permits the synthesis of muscle-specific proteins and is probably identical to G0. The second restriction point, G1q, occurs approximately 4 hr later in the G1 portion of the cell cycle and does not permit the synthesis of muscle-specific proteins. Movement of the cells from G1d to G1q occurs when fibroblast growth factor is added to the cells and is reversed when this growth factor is removed. Repression of the synthesis of muscle specific proteins occurs when fibroblast growth factor is added to cells in G1d. In the case of the muscle form of creatine phosphokinase (M-CPK), the decline in the rate synthesis of this protein is a consequence of a decreased level of its mRNA. By contrast, the repression of alpha-actin synthesis, a protein synthesized only in differentiated cells, appears to be controlled at the translational level. The effect of fibroblast growth factor and other mitogens in these cells require activation of tyrosine kinase(s), but the intracellular targets of these kinases are not known. Studies by others suggest that activation of the ras oncogene can mimic the action of mitogenic polypeptides on these and other muscle cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2924755 TI - Is particle board in the home detrimental to health? AB - A questionnaire concerning health and living conditions was sent to the parents of 1387 children aged 0-15 years to answer the question if children living in homes built with large amounts of particle board had more headaches and respiratory and skin symptoms than other children. There were 1376 possible respondents, and of those 1036 (75.3)% returned the questionnaire. Of the questionnaires returned, 972 (70.6%) were analyzable. The children lived in homes with much particle board (group A); little particle board, or homes as group A but treated in a special way (group B); and homes with no particle board (group C). For the 0- to 5-year-old children, living in homes with much particle board was a risk factor for developing wheezy bronchitis, eye and nose irritation, and coughing. For the 6- to 15-year-old children, living in a home with much particle board was not a risk factor. Risk factors for headache, irritation of the throat, and need for daily antiasthmatic medication were analyzed for all the children collectively. Living in a home with much particle board was a risk factor for all three conditions. PMID- 2924756 TI - Lead distribution in rats repeatedly treated with low doses of lead acetate. AB - Male Sprague-Dawley rats were treated with ip injections of lead acetate (10 and 20 mg/kg) at intervals of 1, 2, 4, 8, 12, 16, 20, and 24 weeks. Eight rats from each specified injection group were sacrificed 48 hr after the end of each treatment. Lead was determined in whole blood, plasma, plasma filtrate, saliva, urine, feces, brain, salivary glands, liver, kidney, testes, femur, and fur. In the liver, the concentrations of lead fluctuated; in the salivary glands and the testes, lead levels were low. In the bone, the kidney, and the brain, lead accumulated steadily and reached high levels in bone and renal tissues, but remained low in the brain. Correlation analysis showed a reciprocal relationship between blood-lead and kidney-lead in the rats treated with 10 mg lead acetate/kg (r = 0.898). In the rats treated with 20 mg lead acetate/kg, urine-lead was correlated to kidney-lead (r = 0.820). In both groups of treated rats, fur-lead was correlated to kidney-lead (r = 0.868 and r = 0.905, P less than 0.01) and brain-lead (r = 0.879 and r = 0.946, P less than 0.01). PMID- 2924757 TI - An experimental study of the penetration of polycyclic aromatic hydrocarbons through a model of the bronchial lining layer. AB - The penetration of benzo[a]pyrene (BaP) through a nonbiological experimental model of the bronchial lining layer (BLL) was studied. The purpose was to investigate how the lipid-aqueous structure of the BLL might influence the rate of penetration of polycyclic aromatic hydrocarbons (PAHs) from the ambient air to the bronchial epithelium. The experimental model was built up in a petri dish by (A) a thin layer of paraffin at the bottom, simulating the lipophilic membranes of the epithelial cells; (B) an aqueous starch gel on top of the paraffin, simulating the viscous aqueous region of the BLL; and (C) a thin layer of phosphatidylcholine, simulating the surfactant lipid layer at the air interface. BaP was administered on top of the barrier either diffusely or from a point source, and the penetration was studied by measuring the concentration of BaP as a function of time both in the liquid phase and in the paraffin. Comparisons were made with a purely aqueous barrier without the thin phospholipid layer. The results show that the rate of penetration of BaP through the purely aqueous barrier is orders of magnitude higher than that of the lipid-aqueous barrier. A thin layer of phospholipids at the air interface thus has a tremendous influence on the rate of penetration of lipophilic substances and probably this, rather than the release rate of PAHs from their carrier particles, is the rate determining step in the overall transport of PAHs from such particles to the bronchial epithelium. PMID- 2924758 TI - Residual tetrachloroethylene in dry-cleaned clothes. AB - A large amount of residual tetrachloroethylene (TCE), up to 13.6 mg/g, was found in dry-cleaned clothes. The amounts varied among dry-cleaning establishments as well as with the type of fiber. The causes of these variations are discussed. Air TCE concentrations in the closed environment of dry-cleaning outlets were elevated: the highest reading was 4.8 mg/m3. The expired air of outlet employees also showed an increased level of TCE (average, 36.9 micrograms/m3). Increased air contamination from TCE released from dry-cleaned clothes was also observed in the home of a consumer. To reduce environmental contamination from TCE released from any of these sources, the amount of residual TCE in dry-cleaned clothes should be minimized. PMID- 2924759 TI - Cardiorespiratory strain during walking in snow with boots of different weights. AB - In order to assess the physiological strain of different boot weights, seven male and three female subjects walked on a treadmill and a snow-field while wearing three types of boots: winter jogging boots (WJB), rubber boots (RB), and rubber safety boots (RSB), weighing (means +/- s.d.) 0.9 +/- 0.1, 1.9 +/- 0.4 and 2.5 +/ 0.2 kg, respectively During each walk the subjects wore the same clothing ensembles and moved at the same, individually determined speed. The mean (+/- s.e.) depths of the footprint impression in the snow while walking in the WJB, RB, and RSB were 26.1 +/- 1.5, 25.6 +/- 1.4 and 26.1 +/- 1.5 cm (NS), respectively. During walking on the treadmill, the means for oxygen consumption were 0.79 +/- 0.05, 0.81 +/- 0.06 and 0.83 +/- 0.04 l min-1 (NS) and in snow 2.24 +/- 0.18, 2.34 +/- 0.17 and 2.34 +/- 0.19 l min-1 (p less than 0.01) with the WJB, RB and RSB, respectively. The mean oxygen consumption levels observed during the walks averaged 23% and 65% of the subject's maximum oxygen consumption on the treadmill and in the snow-field, respectively. During the walking tests the corresponding mean heart rates were 106 +/- 4, 93 +/- 5, and 95 +/- 5 beats min-1 (p less than 0.05) on the treadmill, and 151 +/- 11, 150 +/- 11 and 151 +/- 12 beats min-1 (NS) in snow. No significant differences in ratings of perceived exertion were observed between the walking tests in snow with the three types of boots. In accordance with earlier studies, walking in snow was found to be strenuous work. In conclusion, the use of the RSB is recommended during logging work in snow, since they are known to provide greater protection than lighter boots and the increase in physiological strain experienced with RSB in this study was not appreciably greater than that with boots of lighter weight. PMID- 2924760 TI - Effects on load handling of restricted and unrestricted shelf opening clearances. AB - Changes in psychophysical lifting capacity with reductions in shelf opening clearances were experimentally determined. Three levels of shelf opening clearances were studied: unrestricted shelf opening clearance, loose shelf opening clearance (a clearance of 15 mm between the box width and the shelf opening), and tight shelf opening clearance (a clearance of 3 mm between the box width and the shelf opening). Two levels of lifting frequency (1 and 4 lifts/min.) and two lifting heights (floor to 0.81 m and 0.81 m to 1.52 m) were included. The metabolic energy expenditure rates and heart rates of the subjects (8 males and 8 females) at psychophysically acceptable weights of lift were also recorded to assess the physiological burden. The results indicated a decline in the psychophysical lifting capacity of the subjects as the shelf opening clearance became narrower. The decline in psychophysical capacity, compared to unrestricted shelf opening clearance for males was 9% when the shelf opening clearance was 15 mm. A further decline of almost 4% was recorded when the shelf opening clearance narrowed down to 3 mm. For females, the corresponding declines were approximately 10% and 4%. The effects of lifting frequency and height of lift were found to be consistent with previous findings. PMID- 2924761 TI - Effects of frequency and load to lift on endurance time. AB - The purpose of the present study was to determine endurance time for manual lifting tasks which were performed over a wide range of loads (5, 10, 15, and 20 kg) and frequencies (4, 6, 8, and 10 times/min) for a lift from floor to table height. Endurance time was defined in this study as the maximum length of time during which an individual was capable of lifting a given load at a given frequency continuously. The upper limit of endurance time was set to 8 h. Eleven male subjects participated in this study, and the lifting technique utilized with the straight back-bent knees method. The results showed that endurance time was significantly reduced with an increase in frequency or load of lift. The lightest frequency-load combination (4 times/min; 5 kg) was maintained by most of the subjects for 8 h. Conversely, the average endurance time for the heaviest frequency-load combination (10 times/min; 20 kg) was about 27 minutes. PMID- 2924762 TI - Occupational lifting by nursing aides and warehouse workers. AB - Nursing aides (18 women and six men) at one traditional and one modern geriatric ward, and warehouse workers (16 men) at two different types of warehouse departments were studied during occupational work. The vertical load during manual handling was measured using strain gauges built into wooden shoes. The warehouse workers performed four times as many lifts as the nursing aides and transferred five times as great a mass per unit time. Less than 25% of the lifts were carried out with the load evenly distributed on both feet during both the upward lift and lowering. In the warehouses the lifts were short, while the nursing aides were exposed both to lifts of longer duration and to carrying, as well as a greater frequency of unexpected, sudden and high peak load. The heart rate and oxygen uptake values recorded were relatively low, and both groups utilized approximately 25% of their maximum aerobic power. According to official occupational injury statistics, both warehouse workers and nursing aides belong to risk groups with a high frequency of reported back injuries. However, more injuries are reported by nursing aides than by warehouse workers. Greater muscle strength in male workers may partly explain this difference. Qualitative differences in the design of the lifting work, with more lifts of long duration in awkward work postures, more carrying, more exertion of horizontal forces and a greater frequency of unexpected rapid lifts in the nursing aides may also contribute to the differences in risk of injury between these occupational groups. Considerable differences were found between the two hospital wards as regards lifting frequency, force, duration and the proportion of lifts with an even distribution of load on both feet during upward lift. The lifting work was approximately 50% less in the modern ward, which has easily maneuvered electric overhead hoists, spacious premises and better work organization than in the traditional ward, even though the patient handling needs were equivalent. In the warehouse department at which the wares were stored with easy access, the frequency of lifts with an even distribution of load on both feet was approximately 25%, compared to 7% in the other warehouse department. In conclusion, evaluations of occupational lifting work should include a quantitative assessment of the duration and load distribution of lifting, as well as of postures. Workstation design, technical aids and work organization have a profound effect on the lifting work load even in jobs with equal manual handling demands. PMID- 2924763 TI - Circadian specificity in exercise training. AB - The purpose of this study was to determine whether metabolic and cardiorespiratory adaptations to exercise training are greater at the time of day of training than at another time. Twenty-seven subjects performed cycle ergometer tests in the morning (AM) and in the afternoon (PM) before and after a 6-wk period during which ten subjects trained regularly in the morning, seven subjects trained in the afternoon, and ten did not train. Training caused decreases in HR, VE, and rating of perceived exertion during submaximal exercise; a 7.7% increase (p less than 0.01) in VO2 max; and a 9.1% increase (p less than 0.01) in performance time. Adaptations (training effects) were independent of time of day of training for all variables except VO2 at the ventilatory threshold. Compared with each other, subjects who trained in the morning had relatively higher post training thresholds in the morning, while subjects who trained in the afternoon had relatively higher values in the afternoon (p less than 0.05). This is evidence of circadian specificity in training and supports the notion of planning physical preparation to coincide with the time of day at which one's critical performance is scheduled. PMID- 2924764 TI - Biomechanical analysis and assessment of lumbar stress during load lifting using a dynamic 19-segment human model. AB - A dynamic biomechanical human model is presented which allows the quantification of mechanical parameters such as torque, compressive and shear forces, and pressure at the lumbar intervertebral discs. The human model comprises a total of 19 body segments. Various trunk flexions can be analysed due to the provision of 5 joints at the level of the 5 lumbar intervertebral discs. The influence of intraabdominal pressure on spinal load is considered. The inclusion of the influences of gravity and inertia permits the analysis of both static body postures and dynamic body movements. Since the model is 3-dimensional, the lumbar stress can be calculated during both symmetrical tasks in the median sagittal plane as well as during non-symmetrical ones. The influences on spinal stress of trunk inclination and the position of an external load relative to the body are quantified for various load weights up to 50 kg. The torque at the lumbo-sacral joint L5-S1 lies, dependent on posture and load lever-arm, within the range between 0 and 500 Nm; the compressive force on L5-S1 lies within the range between 0.4 and 10 kN, and the shear force at L5-S1 between 0.2 and 0.9 kN. The influences of lift velocity and jerky movement on lumbar stress are quantified. Simulated humpback and hollow-back postures are studied. The compressive forces at the 5 lumbar intervertebral discs are compared. The validity of the model is examined by comparing the model calculations with the intradiscal pressure measurements taken from the literature. Strength tests on lumbar intervertebral discs and vertebrae are collated from the literature in order to assess the lumbar stress during load lifting. The lumbar ultimate compression strength varies within a wide range. The mean value for a total of 307 lumbar segments amounts to 4.4 kN, the standard deviation to 1.9 kN. In conclusion, lumbar compressive force values during lifting fall within the same range as the strength values for the human lumbar spine. PMID- 2924765 TI - Identification of proteins secreted from axons of embryonic dorsal-root-ganglia neurons. AB - Secretion of proteins from the growth cone has been implicated in axon growth and synapse formation and might be involved in the transmission of a variety of axon derived regulatory signals during neurogenesis. In order to identify axonally secreted proteins, dorsal-root-ganglia neurons from chicken embryos were cultured in a compartmentalized cell culture system that allows separate access to neuronal cell somas and axons. The proteins synthesized by the neurons were metabolically labeled by addition of [35S]methionine to the compartment containing the cell somas; the proteins released from the axons were harvested from the culture medium of the axonal compartment. Two-dimensional gel electrophoresis revealed two axonally secreted proteins with apparent molecular mass of 132-140 kDa and 54-60 kDa; they were termed axonin-1 and axonin-2, respectively. Both axonins were found to be secreted from a variety of neuronal cell cultures, but not from any of the nonneuronal cultures investigated, and hence might be neuron-specific. Virtual absence of these proteins from the axonal protein pattern suggests constitutive secretion. The information acquired on coordinates and spot morphology of these proteins in two-dimensional gel electrophoresis provides a useful assay for their purification. PMID- 2924766 TI - Transfection of hepatic genes into adult rat hepatocytes in primary culture and their tissue-specific expression. AB - We describe in this paper a method for studying transient gene expression in a primary culture of adult rat hepatocytes. After isolation by collagenase perfusion, hepatocytes in a monolayer were transfected with foreign DNA by the calcium phosphate precipitation technique during the first 24 hours after plating. When they were transfected with a plasmid containing the gene for chloramphenicol acetyltransferase driven by the early promoter of simian virus 40, hepatocytes reproducibly expressed high levels of chloramphenicol acetyltransferase (CAT); this transient expression was much higher than that obtained with the rat hepatoma cell line H4II. Different medium conditions have been tested; an optimal level of CAT activity can be obtained using a serum-free, hormonally defined medium. Using these techniques, we have investigated the expression of liver-specific genes transferred into hepatocytes. We show that the L-pyruvate kinase promoter is active in these hepatocytes while it is silent in fibroblasts. Moreover, the use of serum-free medium may allow investigation of the role of hormones and nutrients in cells which respond normally to these effectors. PMID- 2924767 TI - A new crystal form of ricin-OR. AB - Ricin-OR, an antitumor toxin, has been crystallized in space group P2 with cell parameters a = 8.77 nm, b = 4.64 nm, c = 7.64 nm and beta = 101 degrees. There is one molecule in the asymmetric unit and the solvent content is estimated to be 48% by volume. The crystals diffract to 0.25 nm resolution which is higher than that of the previously reported C2 crystal form which had a solvent content of 65%. PMID- 2924768 TI - Nuclear basic protein transition during sperm differentiation. Primary structure of the spermatid-specific protein S2 from the dog-fish Scylliorhinus caniculus. AB - The remodeling of nucleoproteins during dog-fish spermiogenesis involves two successive nuclear protein transitions: the first from somatic-type histones to transition proteins during the nuclear elongation of spermatids and the second leading to protamine-DNA association in mature spermatozoa. The chromatin of elongating spermatids contains two transition proteins called S1 and S2. The amino acid sequence of protein S1, a polypeptide of 87 residues was determined previously [Chauviere, M., Martinage, A., Briand, G., Sautiere, P. & Chevaillier, Ph. (1987) Eur. J. Biochem. 169, 105-111]. In the present paper, we report the elucidation of the primary structure of the minor transition protein S2 established by automated Edman degradation of the protein and of its fragments generated by cleavage at methionine and aspartate residues. S2 contains 80 residues and has a molecular mass of 9726 Da. S2 is mainly characterized by a high content of basic amino acids mostly represented by lysine, a relatively high level of hydrophobic residues, the presence of six phosphorylatable residues and the lack of cysteine. Its amino acid sequence shows that the N-terminal half is highly basic, while the acidic residues are located in the C-terminal part of the protein where more diversity in amino acids is noticed. The two transition proteins S1 and S2 share striking structural similarities. Few but significative similarities have been detected with the mammalian transition protein TP1 [Kistler, W. S., Noyes, C., Hsu, R. & Heinrikson, R. L. (1975) J. Biol. Chem. 250, 1847-1853], suggesting similar functions for all these proteins in chromatin remodeling during sperm differentiation. By contrast, the two dog-fish spermatid specific proteins are structurally unrelated to sperm protamines and cannot be considered as their precursors. PMID- 2924769 TI - Solution conformation of sialosylcerebroside (GM4) and its NeuAc(alpha 2----3)Gal beta sugar component. AB - The solution conformations of GM4 ganglioside [NeuAc(alpha 2----3)Gal (beta 1--- 1)Cer] in (2H3C)2SO and its component disaccharide in 2H2O were investigated with the aid of 1H-nuclear magnetic resonance spectroscopy (nuclear Overhauser effect, analysis of coupling constants) and by energy-minimum calculations. The existence of three low-energy conformers obtained by theoretical calculations was supported by experimental findings in the case of GM4, whereas the disaccharide appears to exist as a mixture of two conformers. PMID- 2924770 TI - Acridine dimers: influence of the intercalating ring and of the linking-chain nature on the equilibrium and kinetic DNA-binding parameters. AB - The rigidity of the linking chain of bifunctional intercalators in the ditercalinium series was shown to be critical for antitumor activity. In order to study the influence of the rigidity of the linking chain on the DNA-binding properties of DNA bifunctional intercalators, fluorescent 9-aminoacridine and 2 methoxy-6-chloro-9-aminoacridine analogues with chains of variable rigidity were synthesized. 1H-NMR studies show that the conformation of 9-aminoacridine dimers is almost independent of the nature of the linking chain. A strong self-stacking of the aromatic rings of the 2-methoxy-6-chloro-9-aminoacridine is observed for dimers with flexible chains but not for those with rigid chains. All the dimers having a linking chain long enough to bisintercalate in DNA according to the excluded site model are indeed bisintercalators. The kinetic association constant of all monomers and dimers for poly[d(A-T)].poly[d(A-T)] are in the same range (2 4 x 10(7) M-1 s-1). The large increase of DNA binding affinity observed for the dimers is always associated with the expected decrease of the dissociation rate constant. The effect of chain rigidity and pH on the calf thymus DNA binding of 9 aminoacridine and 2-methoxy-6-chloro-9-aminoacridine dimers is quite different. In the series of 9-aminoacridine the pKa of the dimers remains high and therefore no difference of DNA-binding affinity is observed between pH 5 and 7.4. The rigidity of the linking chain does not significantly alter the DNA-binding affinity. In the 2-methoxy-6-chloro-9-aminoacridine series, the pKa of all dimers became smaller than the physiological pH and a dramatic decrease of DNA-binding affinity is observed when the pH is increased from pH 5 to 7.4. This decrease appears significantly smaller for dimers with rigid chains. A similar dramatic decrease of binding affinity at pH 7.4 is not observed for poly[d(A-T)].poly[d(A T)]. This factor makes these dimers strongly specific for the alternating polymer at pH 7.4. PMID- 2924771 TI - Role of a sulfhydryl group in gastric lipases. A binding study using the monomolecular-film technique. AB - Native human and rabbit gastric lipases (HGL and RGL, respectively) were inactivated after modification of one sulfhydryl group/enzyme molecule. HGL and RGL were covalently labeled using 5,5'-dithiobis(2-nitro-[14C]benzoic acid) and the interaction of 2-nitro-5-thio-[14C]benzoic-acid-labeled lipases ([14C]Nbs lipases) with monomolecular lipid films was investigated. Our results show that [14C]Nbs-lipases bind to lipid films as efficiently as native HGL or RGL. The critical surface pressure pi c and the maximal surface pressure (delta pi max) of [14C]Nbs-lipases were enhanced in comparison with those of native RGL and HGL. These changes in behavior were probably due to an increase in hydrophobicity brought about, directly or indirectly, by the binding of the Nbs radical. This chemical modification thus blocks the hydrolysis site and reinforces the hydrophobic character of the gastric lipases. PMID- 2924772 TI - The stereospecificity of the ferrous-ion-dependent alcohol dehydrogenase from Zymomonas mobilis. AB - Alcohol dehydrogenase from Zymomonas mobilis has been found to transfer the pro-R hydrogen of NADH to acetaldehyde. This is the first report of the stereospecificity of a dehydrogenase in the mechanistic and structural class of Fe2+-dependent alcohol dehydrogenases and offers an opportunity to expand mechanistic hypotheses relating stereospecificity, reaction mechanism and reaction thermodynamics in dehydrogenases. PMID- 2924773 TI - Inhibition and active-site modelling of prolidase. AB - Consideration of the active-site model of prolidase led us to examine azetidine, pyrrolidine and piperidine substrate analogs as potential in vivo inhibitors of the enzyme. One of these, N-benzyloxycarbonyl-L-proline, was shown to be a potent competitive inhibitor of porcine kidney prolidase (Ki = 90 microM); its rapid protein-mediated permeation of human and sheep erythrocytes suggests that it may be effective in vivo. The higher homolog, N-benzyloxycarbonyl-L-pipecolic acid, was also a potent inhibitor of the enzyme while the antihypertensive drugs, captopril and enalaprilat, were shown to have mild and no inhibitory effects, respectively. Analysis of inhibitor action and consideration of X-ray crystallographic data of relevant Mn2+ complexes allowed the active-site model of prolidase to be further refined; a new model is presented in which the substrate acts as a bidentate ligand towards the active-site manganous ion. Various aspects of the new model help to explain why Mn2+ has been 'chosen' by the enzyme in preference to other biologically available metal ions. PMID- 2924774 TI - Comparison of computer simulations of the F-type and L-type non-oxidative hexose monophosphate shunts with 31P-NMR experimental data from human erythrocytes. AB - Mathematical modelling was used to predict the behaviour of the two most favoured schemes for the operation of the non-oxidative hexose monophosphate shunt (HMS), the F-type and the L-type pathways. The models simulate the time courses of sugar phosphate concentrations when various substrates are metabolized via each pathway. A 31P-NMR technique, with which to observe time courses of concentrations of sugar phosphates in a human red cell lysate, was developed. The accuracy of each hypothesised scheme was then evaluated by comparing predicted with observed data. The results were more consistent with time courses of sugar phosphate levels predicted by the F-type (classical) pathway than those predicted by the L-type model. However, the accumulation of sedoheptulose 1,7-bisphosphate when a haemolysate was incubated with ribose 5-phosphated showed that the F-type pathway is not a complete description of the system of reactions. Transaldolase was demonstrated to be essential for the normal metabolism of sugar phosphates by haemolysates. The effects of the heat-inactivation of transaldolase on the metabolism of sugar phosphates were accurately predicted by the F-type model. The relevance of attempting to describe the reaction of the non-oxidative HMS as a distinct 'pathway' or 'cycle' is discussed. PMID- 2924775 TI - In vivo 31P- and 13C-NMR studies of ATP synthesis and methane formation by Methanosarcina barkeri. AB - Carbon and phosphorus metabolism of cell suspensions of Methanosarcina barkeri strain MS (DSM 800), grown on methanol, were probed in vivo by NMR. The experimental conditions, which involved thick cell suspensions, did not significantly affect the efficiency of the rate of methanol uptake by cells. Following exposure to methanol an acidification of both the intracellular and the extracellular spaces was observed and a gradient of 0.5 pH units across the cytoplasmic membrane was determined from the 31P-NMR data. High levels of intracellular ATP up to 4 mM were detected. The ADP concentration determined in a suspension of starved cells was only 2 mM, suggesting that a significant amount of ADP may be immobilized and is thus not detectable by NMR. In the presence of the protonophore, 3,3',4',5-tetrachlorosalicylanilide, the proton gradient was dissipated and the synthesis of ATP stopped. The inhibitor of the ATP synthase, N,N'-dicyclohexylcarbodiimide, was rather inefficient in inhibiting ATP synthesis. High concentrations of N,N'-dicyclohexylcarbodiimide (corresponding to 300 nmol/mg protein-1) were required to decrease the ATP content by approximately 60%, and, under these conditions, formation of acetyl phosphate was detected. However, the methanol consumption rate was not affected. PMID- 2924776 TI - Generation of hydrogen peroxide by cerebral-cortex synaptosomes. Stimulation by ionomycin and plasma-membrane depolarization. AB - Guinea-pig cerebral cortex synaptosomes steadily release H2O2 into the suspending medium, at the rate of 20-30 pmol min-1 mg protein-1. A transient increase of the H2O2 release is induced by the addition of 1 mM Ca2+, which declines within 60-90 s to a rate identical or slightly higher than that before Ca2+. The extra H2O2 following Ca2+ addition varies between 40-100 pmol/mg protein and is insensitive to verapamil. The H2O2 release increases strongly (up to 250 pmol min-1 mg-1) upon depletion of the synaptosomal glutathione by treatment with 1-chloro-2,4 dinitrobenzene, a substrate for glutathione transferase. This treatment however has no effect on the Ca2+-induced H2O2 transient. In these treated synaptosomes a further increase of the output of H2O2 is rapidly induced upon addition of the Ca2+ ionophore ionomycin. This increase (about 100 pmol min-1 mg-1) lasts several minutes and requires the presence of Ca2+. A similar, though less pronounced increased H2O2 release is obtained (also in the absence of Ca2+) upon depolarization of the synaptosomal plasma membrane with KCl or with veratridine. PMID- 2924778 TI - Incidence of arrhythmias after atrial or dual-chamber pacemaker implantation. AB - The incidence of sustained atrial, pacemaker-mediated and ventricular rhythm disturbances was studied retrospectively in a consecutive series of 112 patients without a history of preexisting atrial tachyarrhythmias, receiving an atrial or dual-chamber pacemaker. Early atrial fibrillation (during the first week) was recorded twice. Late atrial fibrillation was seen in seven patients, flutter in one, yielding a total incidence of 8.9% for 22 months. There were no significant differences with respect to age, aetiology, electrocardiographic diagnosis, pacing history, or the measured intracardiac P wave between the group with and the group without atrial fibrillation. Treatment with digoxin reverted three patients to sinus rhythm, association of digoxin and amiodarone, six patients. One patient with congestive heart failure remained in atrial fibrillation. Pacemaker-mediated tachycardia was not a major problem. One patient of a subgroup with known ventricular arrhythmia had a non-sustained ventricular tachycardia during programming at follow-up; sustained ventricular tachycardia was not recorded. Reprogramming to VDD, DVI or VVI was done in 6/100 patients. The incidence of atrial fibrillation or flutter in highly selected patients with dual chamber or atrial pacing is moderately low. It is not possible to identify patients with a high risk for development of atrial fibrillation; when it occurs, it is easily controlled with drugs. DDD pacing seems to be safe in patients with a history of serious ventricular arrhythmias, treated with appropriate drugs. PMID- 2924777 TI - cDNA sequence of adrenodoxin reductase. Identification of NADP-binding sites in oxidoreductases. AB - Adrenodoxin reductase is an NADP dependent flavoenzyme which functions as the reductase of mitochondrial P 450 systems. We sequenced two adrenodoxin reductase cDNAs isolated from a bovine adrenal cortex cDNA library. The deduced amino acid sequence shows no similarity to the sequence of the microsomal P 450 systems or other known protein sequences. Nonetheless, by sequence analysis and c comparisons with known sequences of dinucleotide-binding folds of two NADP binding flavoenzymes, two regions of adrenodoxin reductase sequence were identified as the FAD- and NADP-binding sites. These analyses revealed a consensus sequence for the NADP-binding dinucleotide fold (GXGXXAXXXAXXXXXXG, in one-letter amino acid code) that differs from FAD and NAD-binding dinucleotide fold sequences. In the data base of protein sequences, the NADP-binding-site sequence appears solely in NADP-dependent enzymes, the binding sites of which were not known to date. Thus, this sequence may be used for identification of a certain type of NADP-binding site of enzymes that show no significant sequence similarity. PMID- 2924780 TI - Induction of complete AV block in dogs by transcatheter ablation using high frequency current: an alternative to direct-current high energy shock. AB - The utility of high-frequency current applied through the distal electrode of a conventional electrode-catheter for altering atrio-ventricular conduction was studied in 18 anaesthetized dogs. Following adequate unipolar His bundle recording, current was applied over periods of 20-30 s, with an output power of 30 W. Complete AV block was achieved in all dogs (four dogs on the third attempt, five on the second, and nine on the first). Ten of the dogs were killed after four hours of continuous ECG monitoring (Group I); examination revealed circumscribed spheroidal myocardial lesions at the base of the right atrium over the posterior tricuspid valve; no thrombus formation was encountered. The remaining eight dogs (Group II) were kept alive for three months during which complete block persisted in all cases. The histologic study showed partial replacement of AV nodal and His bundle tissues and myocardium by fibrous tissue. In conclusion, electro-catheter ablation using high-frequency energy is effective for producing complete AV block. The resulting lesions are circumscribed. This method may prove to be an alternative to the transcatheter DC shock for ablation of the AV conduction system. PMID- 2924779 TI - The effect of respiration on diastolic blood flow velocities in the human heart. AB - This study was performed to evaluate the effects of respiration on diastolic blood flow velocity and its relevance for the determination of pulsed Doppler reference values from diastolic blood flow. Doppler signals were recorded from both the atrial and ventricular sides of the mitral valve and the tricuspid valve in 215 healthy volunteers (120 males and 95 females, with ages ranging from 1-65 years). Respiratory signals were recorded simultaneously by a mercury strain gauge around the thorax. From the medians of Doppler spectra the maximum velocity during early diastole (VmaxE), during atrial contraction (VmaxA) and the ratio between VmaxE and VmaxA (EA ratio) were obtained. On the atrial side of the tricuspid valve, VmaxE and VmaxA were significantly higher during inspiration than during expiration. On the ventricular side of the tricuspid valve, this was only found for VmaxE. On the atrial side of the mitral valve, VmaxE and VmaxA were significantly lower during inspiration than during expiration. At the ventricular side of the mitral valve, this was found only for VmaxE. No significant effect of respiration was found on the EA ratio. We conclude that there is a respiration-related effect on VmaxE and VmaxA. However, no significant effect is found on the EA ratio. Thus, for the determination of the EA ratio in intersubject studies, information about the respiratory cycle is not relevant. PMID- 2924781 TI - A prospective study comparing the haemodynamic with the cross-sectional echocardiographic diagnosis of rheumatic tricuspid stenosis. AB - The value of cross-sectional echocardiography in the diagnosis of tricuspid valve stenosis is not clearly established. We prospectively studied by cardiac catheterization 42 consecutive patients, with a mean age of 29 +/- 11 years, who exhibited the cross-sectional echocardiographic features of tricuspid valve stenosis, defined as: diastolic doming of all three tricuspid leaflets and leaflet thickening with restrictive motion. To expose occult and amplify borderline tricuspid diastolic gradients, simultaneous right atrial and right ventricular pressures were recorded in the basal state, after incremental infusions of normal saline to 200, 400, 500, 700 or 1000 ml until a mean right atrial pressure of 12 mmHg was achieved, and finally after intravenous administration of 0.6 mg of atropine. Eighteen patients, Group 1, (43%) exhibited mean tricuspid diastolic gradients greater than 2 mmHg after saline infusion, increasing from a mean of 4 +/- 2 to 9 +/- 3 mmHg, (P less than 0.001), 14 (33%) having gradients greater than 2 mmHg in the basal state, together with four (10%) increasing from 1.7 +/- 0.2 to 4.5 +/- 1.2 mmHg (P less than 0.01) after provocation with fluid challenge. In the remaining 24 patients, Group 2, (57%) the mean tricuspid diastolic gradient was less than 2 mmHg, both at rest and after provocative manoeuvres. We conclude that the cross-sectional echocardiographic features of tricuspid valve stenosis are not a precise indicator of tricuspid valve stenosis. Provocative manoeuvres during haemodynamic studies are required to expose occult or amplify borderline tricuspid diastolic gradients in a minority of patients with the cross-sectional echocardiographic features of tricuspid stenosis. PMID- 2924782 TI - Long-term follow-up of patients with unexplained syncope and negative electrophysiologic study. AB - Fifty-eight patients (29 M, 29 F, mean age 60.8 +/- 16 years) with unexplained syncope at the end of a complete clinical and electrophysiological evaluation, were followed for a mean period of 36.6 +/- 20.5 months (median: 30.5 months). Structural heart disease was present in 32 patients (55.2%). The standard ECG was normal in 24 (41.4%) and showed sinus bradycardia (greater than 40 m-1) and/or first degree AV block and/or intraventricular conduction disturbances in 29 patients (50%). During follow-up, recurrences of syncope were observed in 11 of 43 untreated patients (25.6%), three of seven electrically treated patients (42.9%) and two of eight pharmacologically treated patients (25%). The cause of these recurrences was cardiac in one (1.7%), non-cardiac in 10 (17.2%) and remained undetermined in five (8.6%). Sudden death occurred in only one patient (1.7%), who was receiving chronic amiodarone therapy. These results indicate that (1) syncopal recurrences may occur in an appreciable percentage of patients with unexplained syncope and a negative electrophysiologic study during a relatively long-term follow-up, (2) syncopal recurrences, when they occur, are generally due to a non-cardiac cause, (3) sudden death is an occasional and rare event in this patient population and (4) empirical prophylactic treatment with a permanent pacemaker or antiarrhythmic drugs does not usually prevent complications during the follow-up. PMID- 2924783 TI - Value of induction of pleomorphic ventricular tachycardia during programmed stimulation. AB - The morphology of the first documented, the recurrent and the induced ventricular tachycardia were studied in 41 patients with an old myocardial infarction and documented sustained ventricular tachycardia. During a mean follow-up of 29 +/- 11 months recurrent ventricular tachycardia was present in 24 of 41 patients with the same morphology as the first ventricular tachycardia in nine (37.5%) and a different morphology in 15 patients (62.5%). Ventricular tachycardia with the same morphology as the spontaneous ventricular tachycardia were induced without significant differences between patients with recurrent events and those without. However, multiple morphologies of ventricular tachycardia (pleomorphism) were induced more frequently in patients with subsequent recurrence of ventricular tachycardia (off drugs: 9 of 13, 69%, on drugs: 14 of 23, 61%) than in patients without (off drugs: 4 of 10, 40%, on drugs: 2 of 11, 18%) (P less than 0.05). Pleomorphism of ventricular tachycardia induced during programmed stimulation identifies patients at a higher risk of subsequent recurrent events. Recurrent ventricular tachycardia has a different morphology than the first one in two thirds of patients. PMID- 2924784 TI - Increased mortality in men with ST segment depression during 24 h ambulatory long term ECG recording. Results from prospective population study 'Men born in 1914', from Malmo, Sweden. AB - 'Men born in 1914', from Malmo, Sweden, is a cohort study of the morbidity and mortality of cardiovascular diseases among 68-year-old men in an urban population. Ambulatory long-term ECG recording was part of the health examination that these men were invited to undergo in 1982. Five hundred attended (80.5%) of the 621 invited. Ninety-eight of the 394 men in whom the ECG recording was technically satisfactory had at least one episode with horizontal or downsloping ST segment depression greater than or equal to 0.1 mV. The median total duration of ST segment depression was 135 min. 90% of these episodes were not preceeded by any increase in heart rate. In only eight of the 47 men who reported an occurrence of chest symptoms during the recording period did ST segment depression and chest symptoms occur simultaneously. 43 months after the health examination, 33 (8.4%) men had died. The mortality in men without ST segment depression and without any history of coronary heart disease was 6.5%. The incidence of fatal and non-fatal myocardial infarction in men without ST depression greater than or equal to 0.1 mV and without a history of IHD was 2.3%. Men with ST depression greater than or equal to 0.1 mV in comparison with this group had a 4.4 times greater relative risk. The risk in men with both ST segment depression greater than or equal to 0.1 mV and history of coronary heart disease was 16.0 times greater. This study shows that asymptomatic ST segment depression is a frequent finding in elderly men. The occurrence of asymptomatic ST segment depression is associated with an increased cardiovascular mortality. This increased mortality is independent of a history compatible with angina pectoris or previous myocardial infarction. PMID- 2924785 TI - Aneurysm of the left anterior descending coronary artery after chest trauma. AB - A 28-year old man developed transmural anterior wall myocardial infarction after a car accident despite the absence of external signs of chest trauma. Coronary angiography one month after the accident demonstrated an aneurysm of the left anterior descending artery. Angiography five and eleven months afterwards showed almost total regression of the aneurysm. The man remained asymptomatic with no signs of residual ischaemia one year after the accident. Blunt trauma to the chest is a well-known cause of cardiac damage including myocardial contusion, rupture of the ventricular wall, septum, papillary muscles or chordae tendineae. Myocardial infarction secondary to distinct injury to a coronary artery has only seldom been described. Visualization of a localized lesion in a coronary artery of an otherwise non-atherosclerotic coronary tree supports the traumatic origin of a myocardial infarction. PMID- 2924786 TI - Ruptured aneurysm of sinus of Valsalva co-existing with a single coronary artery. AB - The clinical and surgical findings in a 41-year-old male with the unusual co existence of a ruptured sinus of Valsalva aneurysm and a single coronary artery are described. The literature is reviewed and the significance of a single coronary artery discussed. PMID- 2924787 TI - Multiple extra-adrenal paragangliomas associated with catecholamine cardiomyopathy. AB - We describe a patient with multiple extra-adrenal paragangliomas who presented with clinical features of a dilated cardiomyopathy. Hypertension was not a major feature of the illness despite excessive catecholamine secretion by the tumours. Following surgical resection the changes of dilated cardiomyopathy did not regress on echocardiography and the patient died of left ventricular failure. PMID- 2924788 TI - Anterior mitral valve aneurysm perforation secondary to aortic valve endocarditis detected by Doppler colour flow mapping. AB - We report a case of mitral valve aneurysm formation and perforation, secondary to Streptococcus sanguis endocarditis of the aortic valve. Aneurysm formation was documented by cross-sectional echocardiography and its perforation was established by Doppler colour flow mapping, and subsequently confirmed at surgery. PMID- 2924789 TI - Aneurysms of the sinuses of Valsalva in Noonan's syndrome. AB - A case of Noonan's syndrome with aneurysmal dilatation of the sinuses of Valsalva is described. Enlargement of the left heart border on the postero-anterior chest radiograph was initially interpreted as dilatation of main pulmonary artery but aortography confirmed the presence of large aneurysms of two of the sinuses of Valsalva. Connective tissue abnormalities, known to occur in Noonan's syndrome, could be responsible for aortic abnormalities in this syndrome. PMID- 2924790 TI - Diagnosis of a quadricuspid aortic valve by echocardiography has been reported in only three cases. PMID- 2924791 TI - First International Conference on 3-D Image Processing in Microscopy. Gissen, 9 11 March 1988. Abstracts. PMID- 2924792 TI - Annual meeting of the Deutsche Gesellschaft fur Zellbiologie. Bielefeld, 13-17 March 1989. Abstracts. PMID- 2924793 TI - Six postschool case studies of mildly learning handicapped young adults. AB - Participant observation was conducted for 1 year with six mildly learning handicapped young adults following their graduation from high school. Close attention was paid to the ways in which they managed the transition out of school and into more adult roles. During this year, all six floundered from job to job, class to class, and school to school. They expressed discontent and frustration with their present situation. They were at a loss to plan for the future and maintained an unrealistic appraisal of their skills. Their sense of self waxed and waned in keeping with their prospects, and the patience and frustration of family members vacillated as well. PMID- 2924794 TI - Play behavior of hearing impaired children: integrated and segregated settings. AB - The free-play behavior of young hearing impaired children in integrated and segregated settings was compared using a multielement baseline design. Two children, aged 3 and 5, were observed using momentary time sampling of their play as they alternated from one setting to the other. Data were collected in ech setting for various categories of play behavior. The categories were derived from the classic play categories of Parten and Smilansky. Results indicate that the children engaged in more socially advanced play in the integrated setting. PMID- 2924795 TI - Lectin-bearing liposomes: differential binding to normal and to transformed mouse fibroblasts. AB - The binding of covalent conjugates of concanavalin A (Con A) or wheat germ agglutinin (WGA) and liposomes (lectin-liposomes) to the surface of normal and transformed mouse fibroblasts was studied. Quantitation of the binding was performed by means of microfluorometry and radioactive lipid label counting using both sparse and dense cell cultures. It was found that 2.5-3 times more lectin conjugated liposomes are bound to L or SV3T3 cells than to the mouse embryo fibroblasts and 3T3 cells in a broad concentration range. The binding of Con A- and WGA-liposomes was inhibited up to 70% in the presence of the corresponding carbohydrate inhibitors. A decreased binding of lectin-liposomes to cells was also observed when cells were pretreated with the free lectin. Trypsinization of the cells resulted in an increase in the Con A-liposomes binding to normal fibroblasts. When free fluorescent Con A or WGA was used in binding studies no profound differences in the binding of lectin to normal or transformed cells were detected. The relation of the lectin-liposome/cell to cell/cell interactions is discussed. PMID- 2924796 TI - The lateral motion of lipid molecules in the apical plasma membrane of endothelial cells is reversibly affected by the presence of cell junctions. AB - As with other epithelia, the question arises of whether the endothelial cell junctions participate in cell polarization, restrict the localization of lipid molecules, and lead to differences in their lateral motion between the apical and basolateral plasma membranes. We found that in bovine aortic endothelium in culture, the localization of the lipophilic probe 5N-(hexadecanoyl) aminofluorescein (HEDAF) was markedly affected by the presence of cell junctions. At confluence, the probe was observed to be restricted to the exoplasmic leaflet of the apical plasmalemma. It was detected in the basal membrane only after disruption of the cell junctions, whereas the cells remained firmly bound to the underlying extracellular matrix. Fluorescence recovery after photobleaching (FRAP) experiments indicated that the endothelial confluent cell monolayer forms a mosaic of closed diffusion areas in which the probe molecules are free to diffuse. For the first time, and using a new mathematical approach, it was possible to estimate the diameter of these diffusion areas. Values in the range 14-33 microns were found which correlate well with the actual measured diameters of 14 to 26 microns for the apical pole of individual cells. Moreover, cell junctions were found to affect the dynamics of the probe. When the cell junctions were disrupted, the lateral diffusion coefficient D of HEDAF was found to be the same in both apical and basal membranes. It regained its initial higher value in the apical poles when cell contacts were restored. This strongly suggests that in vascular endothelium, cell junctions affect overall plasma membrane organization in a reversible manner. PMID- 2924797 TI - Purification of an autocrine growth factor in conditioned medium obtained from primary cultures of scleral fibroblasts of the chick embryo. AB - Scleral fibroblasts of the chick embryo were found to secrete autocrine growth factors. One of the factors was purified from conditioned medium collected from growing-phase cultures of these cells by DEAE-Sepharose column chromatography and following non-denaturing polyacrylamide gel electrophoresis. The specific activity was increased 1100-fold by this purification. The chromatographically purified growth factor was still active after incubation at 95 degrees C, at pH 10 or pH 3, or with glycosidase H, but inactive after incubation with dithiothreitol or trypsin. An active protein having a molecular weight of 32 kDa was found to be the major component of the final preparation. PMID- 2924798 TI - Cell attachment properties of collagen type VI and Arg-Gly-Asp dependent binding to its alpha 2(VI) and alpha 3(VI) chains. AB - Twelve of sixteen different cell types including fibroblasts and tumor cells were able to attach and spread on substrates of pepsin-solubilized or intact collagen VI, and on its triple helical domain. Attachment and spreading were independent of soluble mediator proteins (fibronectin, laminin) and collagen VI was distinct from collagens I, IV and V in the cells with which it interacted. Many of the same cells bound and spread on substrates prepared from unfolded alpha 2(VI) and alpha 3(VI) chains but not on the alpha 1(VI) chain. The interactions with the chains were inhibited by low concentrations (10-100 microM) of synthetic RGDS and RGDT but not RGES peptides while the binding of cells to pepsin-solubilized collagen VI was more than 20-fold less sensitive to these peptides. The data indicate that cells have the ability to bind to collagen VI in a specific manner suggesting a similar function for collagen VI in situ. PMID- 2924799 TI - Collagen processing, crosslinking, and fibril bundle assembly in matrix produced by fibroblasts in long-term cultures supplemented with ascorbic acid. AB - Human foreskin fibroblasts were cultured for up to 6 weeks in medium supplemented with ascorbic acid. During this time, the cells produced an extensive new connective tissue matrix in which the accumulated collagen (mostly type I) amounted to about 0.25 mg/10(6) cells. The matrix was highly differentiated as shown by complete processing of procollagen to collagen alpha-chains and covalent crosslinking of the collagen. Alignment of collagen fibrils occurred as the fibrils were deposited between cells, and binding of adjacent fibrils to the cell surface appeared to hold the fibrils in register. Groups of aligned fibrils were subdivided into bundles by cell-surface folds. If beta-aminopropionitrile was added to the medium, collagen crosslinking was inhibited, but not collagen synthesis or fibril bundle organization. If ascorbic acid was omitted from the culture medium, the extensive new connective tissue matrix was not produced. Our results indicate that fibroblasts in long-term cultures supplemented with ascorbic acid produce a connective tissue matrix with many in vivo-like properties including supermolecular organization of collagen. PMID- 2924800 TI - Compared intracellular localization of the glucocorticosteroid and progesterone receptors: an immunocytochemical study. AB - The intracellular distribution of the glucocorticosteroid and progesterone receptors (GR and PR, respectively) was studied immunohistochemically. In control adrenalectomized (Adx) rat liver, immunostaining of paraffin sections revealed GR in cell nuclei, with a wide range of intensity between individuals. Following dexamethasone (Dex) treatment, the nuclear staining was uniformly high in all animals; the cytoplasmic staining was always weak and remained unchanged after Dex treatment. In frozen sections, the GR immunoreactivity in cell nuclei was weak in the absence and very strong in the presence of Dex, while no GR-specific cytoplasmic staining was observed. In frozen sections fixed in vapor of formaldehyde to avoid any artifactual redistribution of the receptor, some GR immunostaining was observed in the cytoplasm and the nucleus. In contrast, in paraffin as well as in frozen sections of chick oviduct, fixed by immersion or in vapor, PR was exclusively nuclear, including in the absence of progesterone, and the intensity of immunostaining was not modified by progesterone treatment. In order to verify if loss of nuclear receptors during tissue preparation could explain the differences in nuclear immunostaining observed between hormone-free and hormone-occupied GR, and between GR and PR, frozen sections of Adx rat liver and chick oviduct were preincubated at 4 degrees C in buffer solutions before the fixation procedure. It was found that hormone-free GR diffused out of the nucleus faster than hormone-occupied GR nuclei, and that nuclear GR diffused faster than nuclear PR. Based on these results, we propose that, during the fixation procedure, the fraction of nuclear GR which diffuses out of the nucleus is much smaller in the presence than in the absence of Dex. This lesser loss of nuclear GR after Dex treatment results in an increase of immunostaining after hormonal administration, which might have been erroneously interpreted as a sign of translocation from cytoplasm to nucleus. That the nuclear PR detection is not modified by progesterone treatment may be explained by its reduced diffusibility as compared to nuclear GR. This hypothesis does not rule out the existence of some cytoplasmic GR, whose significance remains unclear, but it offers a unified mechanism of action for all steroid hormone receptors. In the case of glucocorticosteroids, as already proposed for estradiol and progesterone, no step of cytoplasm to nucleus translocation would be required for hormone action, and transformation-activation would occur in the nucleus, resulting in tighter binding of the hormone receptor complexes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2924801 TI - Expression, cloning and cDNA sequence of a fibroblast serum-regulated gene encoding a putative actin-associated protein (p27). AB - A cDNA clone for a basic putative actin microfilament-associated protein, p27, highly induced in serum-stimulated NIH 3T3 cells, has been isolated by polyclonal antibodies and sequenced. p27 mRNA is a 1.2-kb molecule which is very low in resting NIH 3T3 cells but can be induced at least 100 times after 8 h of fetal calf serum stimulation. In contrast to other inducible mRNAs, p27 mRNA is stable, and its levels can be superinduced by cycloheximide mainly by prolonging transcription. The lack of expression of this messenger in mouse tissues, as well as in all cell lines so far tested, suggests that p27 may be an fibroblast specific protein. One major open reading frame found in p27 cDNA codes for a 201 amino acid polypeptide not related to any previously described actin-binding protein. Interestingly, it shows alternative hydrophilic and hydrophobic domains of amino acids symmetrically arranged from the middle of the protein. The coordinate induction of p27 and actin mRNAs suggest that p27 may be involved in the cytoskeletal rearrangements induced early in cell growth and proliferation. PMID- 2924803 TI - Concanavalin A inhibits mating type recognition in Tetrahymena. AB - The lectin concanavalin A (Con A) inhibits adhesion of cells of complementary mating types into pairs during conjugation in the ciliate Tetrahymena thermophila. Distinct changes in protein synthesis occur in conjugating Tetrahymena, starting before cells have paired, as a result of a preliminary interaction, costimulation, involving nonadhesive, contact-mediated, specific cell-cell recognition. We report here that ConA inhibits costimulation-induced protein synthesis changes. We interpret this result as evidence that Con A inhibits cellular recognition, independent of cell-cell adhesion, in Tetrahymena. PMID- 2924802 TI - Inhibitors of metalloendoproteases block spiculogenesis in sea urchin primary mesenchyme cells. AB - Metalloendoproteases have been implicated in a variety of fusion processes including plasma membrane fusion and exocytosis. As a prerequisite to skeleton formation in the sea urchin embryo, primary mesenchyme cells undergo fusion via filopodia to form syncytia. The spicule is formed within the syncytial cable by matrix and mineral deposition. To investigate the potential involvement of a metalloendoprotease in spiculogenesis, the effect of inhibitors of this enzyme on skeleton formation was studied. Experiments with primary mesenchyme cells in vitro and in normal embryos revealed that skeleton formation was blocked by these inhibitors. These findings implicate a metalloendoprotease in spiculogenesis; such an enzyme has been demonstrated in homogenates of primary mesenchyme cells. The most likely site of action of the metalloendoprotease is at the cell membrane fusion stage and/or at subsequent events requiring membrane fusion. PMID- 2924804 TI - Reduced DNase I sensitivity of the rearranged c-myc gene in somatic cell hybrids between murine plasmacytoma cells and fibroblasts. AB - In mouse plasmacytoma (MPC) S194, the rearranged c-myc gene was much more sensitive to DNase I digestion than the nonrearranged gene. The sensitivity of the rearranged c-myc was markedly reduced to the same extent as that of the nonrearranged one in hybrids between the MPC cells and the fibroblasts, but not in a hybrid between the MPC and the spleen cells. These results suggest that trans-acting factors in fibroblasts alter the DNase I-sensitive structure of the rearranged c-myc gene. PMID- 2924805 TI - Effects of serum type on growth and permeability properties of cultured endothelial cells. AB - Serum is frequently added to defined basal media as a source of certain nutrients and macromolecular growth factors essential for cell growth. The many different sera commercially available may not be equally suitable for all cell types. The effects of four sera, fetal bovine serum (FBS), calf bovine serum (CS), equine serum (ES-1), and plasma-derived equine serum (ES-2), on growth and permeability properties of cultured porcine endothelial cells were determined. The rate of DNA synthesis, measured as [3H]thymidine incorporation, reached a peak at around 24 h, regardless of serum type, and was most marked with ES-1- or ES-2-treated cells. However, when estimated by total DNA, FBS, CS, or ES-1 treatment resulted in greater cell proliferation than ES-2. Based on protein synthetic rate and total cell protein, both FBS and CS appeared to be most growth supporting. At 72 h after cell plating, albumin passage across cultured endothelial monolayers was elevated in ES-1- and ES-2-treated cells compared with FBS- or CS-treated cells. "Leaky" cell monolayers were most marked with ES-1-treated cells. Cells grown in ES-2- and particularly in ES-1-enriched media were larger and more spindle-shaped compared with the typical cobblestone appearance of cells cultured in media enriched with either FBS or CS. These data suggest that CS, but not ES-1 or ES-2, is an excellent substitute for FBS to support desirable growth properties of macrovascular endothelial cells in culture. PMID- 2924806 TI - The effect of eye-derived-growth-factor (EDGFs) on methionine incorporation in the different cell populations of bovine adult lens in organ culture. AB - When adult bovine lenses were cultured in vitro, the purified retina-derived growth factors EDGF I or EDGF II, as well as the soluble fraction of the retina RE, increased the rate of incorporation of [35S]methionine into protein in cells belonging to different populations in the anterior epithelium as well as in fibers from the most superficial region of the cortex. These fiber cells were the most sensitive to stimulation by the retinal factors as they exhibit a significant increase of total protein synthesis 24 hr after addition of the factors to the culture medium. The epithelial cells studied--central epithelial cells and germinative cells--appeared stimulated only 1 day later. The stimulation of incorporation was not directed towards a particular subset of proteins but to all major polypeptides constituting the electrophoretic pattern of each cell population. It is suggested that this type of ocular signal, which stimulates the expression of a definite program, may act as a permissive signal. PMID- 2924807 TI - Differential assemblage of the basal membrane-cytoskeleton complex in bovine epithelial lens cells. AB - We have investigated the membrane-cytoskeleton complex involved in interactions between the epithelial cells and the capsule of the bovine eye lens. The organization of the molecular complex was determined from cell extraction, immunoprecipitation and immunoblotting experiments and from ultrastructural studies by scanning electron microscopy. We show that marked differences exist in the organization of this basal complex between the central epithelium (mitotic quiescent) and the peripheral epithelium which initiates lenticular differentiation into fibres. Our results support the view that: (a) the organization of several major membrane components in the peripheral epithelium differs from that of the central epithelium; (b) microfilaments and vimentin filaments are independent of each other in the peripheral epithelium, whereas microfilaments are involved in an inter-relationship with vimentin filaments in the central epithelium; (c) two surface proteins of 24 and 27 kD and two surface glycoproteins of 46 and 220 kD appear to be bound to vimentin filaments in the peripheral region, whereas the intermediate filaments appear to be solely in close association with the 46 and 220 kD glycoproteins in the central zone. PMID- 2924808 TI - Racemization of aspartyl residues in proteins from normal and cataractous human lenses: an aging process without involvement in cataract formation. AB - A highly sensitive method was used to determine D- and L-aspartyl residues in protein fractions from normal and cataractous human lenses. A linear relationship with age was found in all fractions from normal lenses. However, no correlation with cataract could be established. It is concluded that racemization of aspartyl residues is a continuous process in eye-lens proteins but plays no role in cataract formation. PMID- 2924809 TI - The human lens epithelium; morphological and ultrastructural changes associated with steroid therapy. AB - A distinct disturbance to the structure of the lens epithelium was observed in cataract patients receiving steroid medication. Of those cataract patients receiving steroids, 83% exhibited a reticulated pattern of intercellular clefts compared to 5% in the control group. The reticulated pattern was shown to be due to the presence of gaps between the lateral borders of the epithelial cells by electron microscopy. A significant correlation between steroid therapy and epithelial disruption was demonstrated. The significance of such epithelial disruption to cataract formation is discussed. PMID- 2924810 TI - Oxidative modifications to crystallins induced in calf lenses in vitro by hydrogen peroxide. AB - Calf lenses which are incubated in solutions of 1-150 mM H2O2 for 24 hr remain clear at 20 degrees C. While insoluble lens protein increases by at most 2-3%, we find extensive oxidation of exposed protein thiols, major shifts in the size distribution of crystallins, and progressive generation of more acidic polypeptides. Some of these oxidative modifications are reversible with reducing agent. beta H-Crystallins are particularly susceptible to oxidation: disulfide bonded soluble aggregates form at low H2O2 levels, while irreversible dissociation to beta L-crystallins occurs at high H2O2 concentration. The gamma crystallins are particularly prone to charge modification. In contrast, the size and charge distributions of alpha-crystallins appear to be virtually unaffected by H2O2. PMID- 2924811 TI - Age-related changes in retinal sensitivity, rhodopsin content and rod outer segment length in hooded rats following low-level lead exposure during development. AB - Electroretinographic, morphometric and cyclic nucleotide metabolism studies in adult hooded rats have established that low-level lead exposure during early postnatal development (postnatal days 0-21) causes long-term selective rod deficits and degeneration. To determine if this same low-level lead exposure during early postnatal development produces immediate and/or long-term alterations in retinal sensitivity we examined ERG b-wave threshold responses in dark-adapted control and lead-exposed rats at 1-, 3- and 12 months of age. In addition, to determine possible sites and mechanisms of action responsible for the observed decreases in retinal sensitivity we analyzed the rhodopsin content per eye, the lambda max of rhodopsin and rod outer segment (ROS) length in superior and inferior posterior retina at 1-, 3- and 12 months of age. Relative to adult (3-month-old) controls whose log threshold was arbitrarily set at 0 log units, the mean log relative threshold in control rats was 0.4 log units at 1 month of age and 0.2 log units at 1 yr of age. In contrast, the mean log relative threshold in lead-exposed rats was 1.3 log units at 1 month of age and 1.1-1.2 log units at 3- and 12 months of age. Thus, compared with controls, retinal sensitivity in lead-exposed rats was decreased approx. 1 log unit at all ages examined. The rhodopsin content per eye in control rats increased 13% between 1- and 3 months of age, reaching an adult value of 1.99 nmol per eye, and then decreased 8% by 1 yr of age. In contrast, the eyes from lead-exposed rats contained 30-34% less rhodopsin at all ages examined. No change in the lambda max of rhodopsin was observed in the retinas from the lead-exposed rats. In both controls and lead-exposed rats, the developmental changes in log b-wave relative threshold were paralleled by linear increases and decreases in rhodopsin content per eye such that a log-linear relation between retinal sensitivity and rhodopsin content per eye existed between 1- and 12 months of age. The developmental changes in the superior and inferior retinal ROS length were similar in control and lead-exposed rats: ROSs were at their adult length at 1 month of age and then slightly decreased by 1 yr of age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2924812 TI - Analysis of the proteins of calf and cow trabecular meshwork: development of a model system to study aging effects and glaucoma. AB - The proteins from the trabecular meshwork (TM) of calf and cow eyes were analysed to determine if differences in composition were present and to examine whether this tissue could be used as a framework for the study of glaucoma. Differences in polypeptide composition or amount of protein could be detected with extractions using either acetic acid, neutral buffers and urea, or guanidine hydrochloride. In general, the results suggest that an aggregation of proteins may be occurring with aging. The acid-soluble fraction of both calf and cow TM resembled older human TM specimens with the most prominent protein around 68 kD. To test the utility of the bovine TM system, a mixed function oxidation system was used to determine how the proteins of the TM would react to oxidative stress. Aggregation of the proteins in calf TM as well as actin could be demonstrated, consistent with the idea that the aggregation seen in the cow TM might be the result of oxidation of this tissue. The present study lays a foundation for future work on bovine TM and is consistent with the hypothesis that aging changes in this tissue might be a result of oxidative processes. PMID- 2924813 TI - Monoclonal antibodies to chicken iodopsin. AB - The protein moiety of chicken iodopsin, R-photopsin, was purified from the chicken retina using a sucrose flotation method followed by two steps of column chromatography. Apparent molecular weights of R-photopsin and scotopsin (the protein moiety of chicken rhodopsin), which was partly purified in the process of purification of R-photopsin, were estimated to be 34,000 and 36,000, respectively, by sodium docecylsulfate-polyacrylamide gel electrophoresis. Using the purified R-photopsin as an antigen, four kinds of hybridoma cells which secreted monoclonal antibodies specific for R-photopsin and iodopsin were prepared. The antibodies thus obtained reacted with neither other chicken cone visual pigments nor rhodopsin as analyzed by immunoblots and immunoprecipitation methods. All the monoclonal antibodies stained the majority of the cone outer segments in chicken retina, while an antiserum raised against cattle rhodopsin stained the rod outer segments as well as some cone outer segments in the retina. PMID- 2924814 TI - Discontinuities of the external limiting membrane in the fovea centralis of the primate retina. AB - In the center of the fovea centralis of retinas of three cynomolgus monkeys, one baboon and one male human, the external limiting membrane contains circumscribed areas in which zonulae adherentes are lacking between cone inner segments and apices of Muller cells. These discontinuities of the external limiting membrane begin about 300 microns from the foveolar center, involving only a few cones. Towards the center of the fovea the discontinuities become larger. PMID- 2924815 TI - Glutathione-dependent enzymes in intact rod outer segments. AB - We have compared the specific activities of glutathione-dependent enzymes in rod outer segments (ROS) and in whole retina of rabbits and rats, using three different assays. In the first, glutathione peroxidase (GSH-Px) activity was measured as the combined activities of the Se-dependent and Se-independent forms using cumene hydroxide as a substrate. In the second, Se-dependent GSH-Px alone was measured using hydrogen peroxide (H2O2) as a substrate. In the third, the combined activities of several enzymes, collectively known as GSH-S-transferase, were measured. The latter includes the activity of the Se-independent GSH-Px. GSH Px activity (Se-dependent and Se-independent combined) in ROS of rat and rabbit were found to be 47.7 +/- 8.2 and 72.9 +/- 11.9 nmol of GSH oxidized min-1 mg-1 soluble protein, respectively. From whole retina, values were 67.3 +/- 6.0 and 128.8 +/- 12.3, respectively. Se-dependent GSH-Px specific activities from the above tissues were 43.5 +/- 2.9 (rat ROS). 70.6 +/- 11.3 (rabbit ROS), 30.6 +/- 9.6 (rat whole retina), and 113.2 +/- 12.2 (rabbit whole retina). GSH-S transferase activity was negligible in rabbit ROS, whereas, in rat ROS, it was 40.4 +/- 8.0, expressed as nmol of S-2,4-dinitrophenylglutathione produced min-1 mg-1 soluble protein. In contrast, the GSH-S-transferase specific activity in whole rabbit retinas was about eight times that found in the rat retina (101.5 +/ 12.3 for rat retina and 885.3 +/- 60.0 for rabbit retina). These results demonstrate that ROS contain glutathione enzymes which are important in protecting membranes from oxidative stresses by reducing hydrogen peroxide and lipid hydroperoxides at the site of their formation. PMID- 2924817 TI - Calcium antagonist-induced relaxation of the prostaglandin-F2 alpha response of isolated calf retinal resistance arteries. AB - The relaxing effect of nitrendipine and D600 on isolated ring segments of calf retinal resistance arteries (i.d. ca. 200 microns) contracted with prostaglandin F2 alpha (PGF2 alpha) or high potassium solution was studied. The vessel response to both PGF2 alpha and potassium stimulation was dependent on extracellular calcium. Removal of extracellular calcium reduced the vessel response to PGF2 alpha and potassium by 85% and 98%, respectively (P less than 0.01). Both calcium antagonists induced a concentration dependent relaxation of PGF2 alpha pre contracted vessels with = -log[IC50(M)]-values of 8.01 and 7.13 for nitrendipine and D600 (P less than 0.05), respectively. The calcium antagonists were equieffective in relaxing the vessels amounting to 33% for nitrendipine at 10(-6) M and 37% for D600 at 10(-5) M. Further analysis of the data revealed that the nitrendipine induced relaxation of the PGF2 alpha response was linearly correlated with the internal lumen diameter of the vessels. No correlation was found for the D600 induced relaxation. At the highest concentrations of nitrendipine, 10(-6) M, and D600, 10(-5) M, the potassium induced response was reduced by 94 and 75%, respectively. The results show that calcium antagonists only partially relax retinal resistance arteries contracted with PGF2 alpha although the vessels are dependent on extracellular calcium for active force generation. Calcium must therefore be activated by PGF2 alpha through other pathways than those blocked by calcium antagonists. PMID- 2924816 TI - Selection of therapeutic agents for intraocular proliferative disease 3. Effects of fluoropyrimidines on cell-mediated contraction of human fibroblasts. AB - We evaluated the efficacy of 5-fluorouracil (5-FU) and 5-fluorouridine (5-FUR) as anticontractile agents in an in vitro model that measures the ability of human and rabbit fibroblasts to contract a collagen gel. Human fibroblasts were more contractile than rabbit fibroblasts, required higher concentrations of 5-FUR for inhibition of contraction, and were able to tolerate higher doses of the drug. 5 FU failed to inhibit contraction of human fibroblasts at concentrations up to 1.5 mM (200 micrograms ml-1), but significantly inhibited rabbit fibroblast contraction, although to a lesser degree than 5-FUR under similar conditions. 5 Fluorouridine (100 microM, 26 micrograms ml-1) inhibited contraction of human fibroblasts by more than 80%, whereas only 10 microM (2.6 micrograms ml-1) 5-FUR was required for 90% inhibition of rabbit fibroblast contraction. 5-FUR was cytotoxic to rabbit fibroblasts at concentrations of 200 microM (52 micrograms ml 1) or greater, but 800 microM was non-toxic to human fibroblasts after 96 hr exposure. At concentrations of 1.5 mM, 5-FU had no significant effects on the viability of either human or rabbit fibroblasts. These results suggest that 5-FUR may prove useful for the treatment of human ocular proliferative disorders in which contraction of fibrocellular elements is thought to play a part. They also suggest that fluoropyrimidine dosages found to be effective in a rabbit model of proliferative vitreoretinopathy may be less effective in humans and that 5-FUR levels shown to be toxic to rabbit-derived cells may be tolerated by humans cells. PMID- 2924818 TI - Response of cultured Muller cells to heat shock--an immunocytochemical study of heat shock and intermediate filament proteins in response to temperature elevation. AB - Muller cells from adult rabbit retina were cultured at normal (37 degrees C) temperature and under heat shock conditions (42-43 degrees C) for either 1.5 hr or 4 hr. The presence of heat shock proteins of three different molecular weights, and of vimentin, was identified by the use of monoclonal antibodies and of GFAP by a suitable polyclonal antibody coupled in each instance with immunofluorescence microscopy or immuno-electron microscopy. Heat shock conditions resulted in the expression of HSP of molecular weights in the ranges 57-61 kD, 68 kD and 90 kD. The high level of expression of GFAP in unshocked Muller cell cultures (80-90% of cells) was reduced after 1.5 hr of heat shock to 20-30% of cells, and after 4 hr to only 5%. Although the expression of vimentin (90% of untreated cells) was only slightly reduced by heat shock (60-80% of cells) the intracellular staining pattern of vimentin was greatly altered by heat shock. Changes in the expression of HSP, GFAP and vimentin can all be regarded as part of the Muller cell response to heat shock conditions. PMID- 2924819 TI - Carcinogenic tryptophan pyrolysis products in human lens. AB - Mutagenic and carcinogenic tryptophan pyrolysis products, 3-amino-1,4-dimethyl-5H pyrido-[4,3-b]indole (Trp-P-1) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P 2), have been identified in human cataractous lenses, but not in young bovine lenses. The amounts of Trp-P-1 and Trp-P-2 in senile cataractous lenses were 156.34 +/- 35.63 fmol (mean +/- S.D., n = 10) and 128.27 +/- 40.45 fmol (n = 10), respectively, while those of Trp-P-1 and Trp-P-2 in diabetic cataractous lenses were 158.29 +/- 40.06 fmol (n = 10) and 150.34 +/- 23.77 fmol (n = 10), respectively. In both senile and diabetic cataractous lenses, the concentrations of Trp-P-1 and Trp-P-2 in the insoluble protein fraction (fmol mg-1 protein) were significantly higher than those in the water-soluble protein fraction. Moreover, proteinase-K treatment of lens protein before extraction with methylene chloride significantly increased the recoveries of Trp-P-1 and Trp-P-2. These results clearly indicate that carcinogenic tryptophan pyrolysis products, gamma-carboline derivatives, are present in human cataractous lenses and that these fluorescent carcinogens are significantly concentrated in the insoluble lens proteins. PMID- 2924820 TI - Intraocular pressure effects of water loading and venous compression tests in normal and denervated pigmented rabbits. AB - We have compared IOP elevations induced by water-loading and by increased cephalic venous pressure in normal and denervated pigmented rabbits. Denervations were performed by sympathetic ganglionectomy and/or blockade of the sensory and autonomic innervation of the eye through retrobulbar anesthesia; retrobulbar anesthesia induced significant decreases of the basal IOP in control but not in ganglionectomized eyes. The water-loading test induced a peak pressure elevation approximately 30 min after water administration that could be counteracted by retrobulbar anesthesia. Ganglionectomized rabbits exhibited steeper IOP rises and greater IOP increases following water-loading than the control eyes; retrobulbar anesthesia in ganglionectomized eyes delayed the IOP response to water-loading. Compressions of the neck lasting 30 min elicited significant IOP elevations that were more pronounced in ganglionectomized eyes. In these eyes, retrobulbar anesthesia further increased the IOP rise elicited by neck compression. An IOP decrease below control values was observed at the end of the venous compression. The results indicate that an intact efferent innervation of the eye contributes to buffer IOP elevations induced by water-loading or cephalic venous stasis, presumably through the vascular effects of the ocular autonomic nerves. PMID- 2924821 TI - Light scattering and photocrosslinking in the calf lens crystallins gamma-II, III and IV. AB - The calf lens proteins gamma-II, -III and -IV crystallin have been photolyzed in pH 7.5 phosphate buffer solution at 25 degrees C. The photolysis light source was either a xenon arc lamp/monochromator system set to pass 290 +/- 5 nm or a nitrogen laser operating at 337.1 nm. Photolysis experiments at 337.1 nm were done both in the presence and absence of added 1.0 x 10(-4) M N-formylkynurenine (NFK). In addition, 1 x 10(-5) M riboflavin was added as a photosensitizer in a few of the experiments. All solutions were 1.0 mg ml-1 protein, and 1.0 ml of solution was irradiated for periods ranging from 10 min to 3 hr. During the 337.1 nm irradiations, the turbidity of the protein solutions was continuously monitored using a He-Ne laser at 632.8 nm. Progress of the 290 nm irradiations was monitored by observing the loss of tryptophan fluorescence for each of the gamma crystallin proteins. The rate of growth of light scattering, upon 337.1 nm irradiation, was greatest for gamma-IV. Addition of NFK caused the rates of growth of UV-induced light scattering of all three gamma crystallins to increase significantly. These rates were in the order: gamma-IV much greater than gamma III greater than gamma-II. Following UV exposure, the protein solutions were analyzed using UV-visible absorption spectroscopy and SDS-PAGE. Irradiated gamma crystallin solutions showed increased optical density throughout the visible region, resulting from solution turbidity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2924822 TI - Raman spectroscopy of calf lens gamma-II crystallin: direct evidence for the formation of mixed disulfide bonds with 2-mercaptoethanol and glutathione. AB - This study presents Raman spectra of calf lens gamma-II crystallin and its reaction products with reduced glutathione, 2-mercaptoethanol and p hydroxymercuribenzoate. The absence of a disulfide vibration in gamma-III crystallin (both in aqueous solution and in lyophilized state) indicates that the seven thiol groups in this protein are resistant to air oxidation, and are capable of maintaining their reduced state in the absence of added reducing agents during isolation. However, treatment of the protein with low molecular weight thiols such as glutathione and 2-mercaptoethanol results in mixed disulfide bonds. We have detected, for the first time, the S--S bond stretching vibration from the mixed disulfides at 510 cm-1, which is very similar to the 508 cm-1 reported for the inter/intramolecular disulfide bonds in intact mouse lenses (Yu, N.-T., DeNagel, D.C., Pruett, P.L. and Kuck, J.F.R., Jr. (1985). Proc. Natl. Acad. Sci. U.S.A., 82, 7965-8). Upon titration with five equivalents of p hydroxymercuribenzoate, a strong Raman line was detected at 345 cm-1, which is tentatively attributed to the Hg--S stretching vibration of the mercaptide complex. The S--H vibration region (2500-2700 cm-1) exhibits two resolved peaks at 2562 and 2580 cm-1 with an intensity ratio of 2:5. Both reactive surface thiol groups and buried cysteines give rise to the S--H vibration at 2580 cm-1. PMID- 2924823 TI - Effect of inhibition of the glutathione redox cycle on the ultrastructure of peroxide-treated rabbit epithelial cells. AB - Our previous studies have shown that exposure of cultured rabbit lenses to physiological levels of hydrogen peroxide, following inhibition of the glutathione redox cycle, leads to the formation of distinct vacuoles in the anterior region of the lens at the germinative zone between the epithelium and lens fibers. In the present study the ultrastructure of H2O2-induced membrane damage in the intact lens and in cultured lens epithelial cells was examined by scanning and transmission electron microscopy (SEM and TEM), following the inhibition of glutathione reductase with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). Lenses treated with BCNU/H2O2 exhibited swollen epithelial cells which were observed only above the peroxide-induced vacuoles. The apical surface of the swollen cells had membrane blebs which protruded into the underlying vacuolar space. The appearance of the blebs coincided with a change in the organization of the layer of microfilaments which is normally associated with the apical surface of the cell. Cultured lens epithelial cells treated with BCNU/H2O2 showed membrane blebs which increased in size and number with the duration of exposure. Initially, the blebs were seen only on certain regions of the cell surface with other regions appearing normal. TEM revealed a disorganization of microfilaments in the BCNU/H2O2 treated cells. Neither BCNU nor H2O2 alone affected the morphology of intact lenses or of cultured lens epithelial cells. In culture, isolated lens epithelial cells exposed to BCNU/H2O2 were more susceptible to damage than contiguous cells. While the exact mechanism by which H2O2-induced damage leads to bleb formation on the cell surface is not known, the inability of the cells to detoxify H2O2 due to the inhibition of glutathione reductase results in the disturbance of membrane cytoskeleton and a focal weakening of the cell surface. These results indicate a correlation between the active glutathione redox cycle in lens epithelium and maintenance of normal cytoskeletal protein organization. PMID- 2924824 TI - Role of microtubules in pigment granule migration in teleost retinal pigment epithelial cells. AB - In cells of the teleost retinal pigment epithelium (RPE), melanin pigment granules migrate in response to changes in environmental light conditions. Melanin granules disperse into the RPE cell's long apical projections in response to the onset of light, and aggregate towards the base of the RPE cell in response to the onset of darkness. The RPE cells possess numerous microtubules and actin filaments, which in the apical projections are aligned longitudinally. Previous cytochalasin studies have shown that intact actin filaments are required for pigment granule dispersion and maintenance of the dispersed state (Burnside, Adler and O'Connor (1983). Invest. Ophthalmol. Vis. Sci. 24, 1). We report here that pigment granule aggregation is strongly inhibited when the highly stable microtubules of RPE apical projections are disrupted by a combination of cold and nocodazole treatments. Pigment dispersion and maintenance of the dispersed and aggregated states are unaffected by microtubule disruption. These results indicate that microtubules are required for RPE pigment aggregation but not for dispersion. PMID- 2924826 TI - Fibrinolytic activity in human tears. PMID- 2924825 TI - NMR pulse relaxation studies on the normal aging and cataractous lens. AB - Proton NMR pulse relaxation experiments have been performed in this and other laboratories mainly on animal lenses and some human lenses. In order to evaluate T1 and T2 analyses as a potentially useful (non-invasive) parameter in delineating lenticular changes in normal aging human rabbit lenses, and in human cataracts, we performed a series of pulse relaxation studies on human eye bank lenses 10 to 93 yr of age, on fresh intact human cataracts and on normal rabbit lenses. Additional spectroscopic studies (fluorescence and 31P-NMR) were also performed on the lenses in order to correlate these parameters with the data relating to 'water phases' in the lens. These experiments demonstrate a potential additional parameter for evaluating 'molecular' changes in the aging and cataractous lens. PMID- 2924827 TI - Multiple inputs to a population of thalamocortical neurons projecting to cat somatosensory cortex. AB - Ninety thalamocortical (TC) neurons were recorded extracellularly in ventrobasal thalamus of halothane-anesthetized cats. Projections of all of these neurons to specific subdivisions of somatosensory cortex were identified by their antidromic invasion following intracortical microstimulation restricted to these subdivisions. Collision-extinction tests were used to document excitatory inputs to TC neurons from afferent fibers of forelimb nerves stimulated electrically. Thirty-nine TC neurons (43% of sample) were excited from at least one forelimb nerve. Fifteen TC neurons were activated from two or more forelimb nerves. Combinations of effective nerves included ones innervating topographically different regions of forelimb. Neurons projecting to area 1-2 were least likely to be activated from more than one nerve. Seven TC neurons activated by electrical stimulation of nerve trunks were tested also with two distinct forms of mechanical somatic stimuli, i.e., hair bending and vibration, and with intradermal electrical stimuli. These tests revealed convergent inputs from hairy and glabrous skin. We conclude that there is a population of neurons, located in ventrobasal thalamus, which is capable of conveying multiple inputs to each of the subdivisions of primary somatosensory cortex. These neurons could be involved in forming properties of feature-extracting neurons of somatosensory cortex. PMID- 2924828 TI - Single medullary reticulospinal neurons exert postsynaptic inhibitory effects via inhibitory interneurons upon alpha-motoneurons innervating cat hindlimb muscles. AB - This study was aimed at elucidating the brainstem-spinal mechanisms of postural suppression evoked by stimulating the dorsal portion of the caudal tegmental field (DTF) in the pons. For this purpose, we first sampled a group of reticulospinal neurons located in the medial part of medullary reticular formation, which were activated orthodromically and antidromically by stimulating the DTF area and the first lumbar spinal segment, respectively (DTF-RS neurons; N = 26). These DTF-RS neurons were located within the nucleus reticularis gigantocellularis (NRGc) and projected their descending axons to the lumbar spinal cord through the ventrolateral funiculus. The postsynaptic inhibitory effects of single DTF-RS neurons upon hindlimb alpha-MNs intracellularly recorded (N = 78) were then studied with spike-triggered averaging. Twelve DTF-RS neurons evoked IPSPs in 21 hindlimb alpha-MNs. Five DTF-RS neurons exerted postsynaptic inhibitory effects upon more than one alpha-MNs. These alpha-MNs were located from L5 to S1 segments of the spinal cord. A mean latency of IPSPs which was measured from the onset of the trigger spike was 5.1 ms with time to peak of 1.8 ms, and the mean segmental delay of the IPSPs was 1.5 ms, which was measured from the onset of the descending axonal volley recorded extracellularly adjacent to alpha-MNs. Amplitudes of the IPSPs were augmented with an increase in the firing frequencies of the DTF-RS neurons, the increase being produced by iontophoretic application of glutamate. These characteristics of the IPSPs suggest that reticular effects are mediated at least by a single spinal inhibitory interneuron. These results suggest that the DTF-NRGc system participates in generalized motor inhibition. PMID- 2924829 TI - Response to rates of luminance change of sustained and transient cells in the cat lateral geniculate nucleus and optic tract. AB - We recorded the response of sustained (X) and transient (Y) cells in the cat lateral geniculate nucleus (LGN) and optic tract to a stationary spot while the spot luminance was increased and decreased with a constant rate (linear luminance functions), or modulated sinusoidally. The spot filled the receptive field center, and was surrounded by an annulus of fixed luminance. The LGN X cells seemed to perform a differentiation-like operation in the time domain at slow temporal modulations, giving information about rate of luminance change. To the linear luminance functions the cells responded with a constant firing rate. The on-center cells were activated during increasing luminance, the off-center cells during decreasing luminance. This firing rate increased monotonically with rate of luminance change. To low-frequency sinusoidal modulations the cells had a marked negative phase shift. The response of the LGN Y cells had a transient component shortly after the luminance started to increase (on-center cells) or decrease (off-center cells), followed by a secondary, gradually changing component. The peak of the transient component occurred on average when the response of the X cells increased most rapidly. To low-frequency sinusoidal modulation the average negative phase shift of this peak was twice the average of the X cells. The Y system could accordingly provide information about rate of change in the response of the X system. In the optic tract the X fiber response resembled the LGN X cell response in most respects. The Y fibers had only a weak transient response component, so this component was accentuated in the thalamic relay. Also the sensitivity for rate of luminance change was increased in LGN. PMID- 2924830 TI - Excitatory interactions between phrenic motoneurons: intracellular study in the cat. AB - 1. Intracellular recordings were made from 220 Phrenic Motoneurons (PM) in anaesthetized, spontaneously breathing cats, deafferented from C3 to C7, in order to look for somatic events related to the Recurrent Responses (RR) evoked in PM axons by repetitive stimulation of the phrenic nerve. RR appear sporadically at a constant latency, originate from a spinal nicotinic mechanism and can be evoked in a PM without the presence of an antidromic volley in its axon (Khatib et al. 1986). 2. Using stimuli effective for eliciting RR in axons, we failed to observe intracellularly somatic events corresponding to RR after the occurrence of an antidromic action potential. RR were observed extracellularly in two cases, but in both cases the recording originated from axons. 3. We attempted to elicit somatic RR without a preceding antidromic action potential, using either parathreshold stimulation of the impaled PM, or suprathreshold stimulation of a phrenic strand which excluded the axon of the impaled PM. In both cases, RR-like events, with very stable latencies, appeared sporadically in 4/142 and 2/15 PMs respectively. 4. Parathreshold stimuli or stimulation of a strand were coupled with averaging of the synaptic noise in order to look for small events temporally related to the stimuli. Short latency small depolarizations, looking-like recurrent EPSPs, were revealed in 22/142 and 5/15 PMs respectively. 5. These results confirm the existence of interrelations between PMs, providing for re excitation and coupling within the phrenic pool, in addition to centrally imposed synchronization. PMID- 2924831 TI - Single unit activity in the auditory cortex of a monkey performing a short term memory task. AB - Short term memory to tones (STMT) was investigated by recording single unit activity in the auditory cortex of a behaving monkey. The activity of each unit was studied in two behavioral conditions: a) During task performance, the monkey had to compare two tones separated by one second of silence (inter-stimulus interval). b) During a non-performing period; the monkey heard the two tones but did not respond behaviorally. It was noted that the firing rate of many units during the inter-stimulus interval (ISI) was dependent on the frequency of the first tone. Such dependency was observed even towards the end of the ISI, both during task performance trials (50% of the units) and during the non-performing period (32% of the units). The activity of these units could be the basis of STMT in both of these behavioral states. In 65% of all the units tested, the responses during the ISI were of a higher magnitude in the performance period than were the responses in the non-performance period. The activity of these units may be related either to general processes such as attention and expectation or to short term memory processes. During task performance, the responses of 23% of the units to the second tone were dependent on whether its frequency was identical to that of the first tone. Such dependency was never observed during the non-performing period. These units may detect similarity or non similarity between two tones presented one second apart. Periodic patterns of firing were not found in the study, thus suggesting that the ISI responses were not generated by reverberatory activity in simple closed loops. On the basis of these results, several alternative mechanisms of STMT are suggested. PMID- 2924832 TI - Retrospective and prospective coding of information: role of the medial prefrontal cortex. AB - Animals with sham-operations or medial prefrontal cortex lesions were trained in a task which required memory for short or long lists of items (spatial locations). On any one trial a rat is presented with 2, 4, 6, 8 or 10 items (spatial locations) on a 12-arm radial maze followed 15 min later by a win-shift test comprising a choice between a place previously visited and a novel place. Sham-operated animals showed an increase in errors as a function of set size (2 to 8 items) followed by a decrease in errors with a set size of 10 items suggesting the use of both retrospective and prospective memory codes. In contrast, animals with medial prefrontal cortex lesions made most of their errors for the longest list length reflecting an inability to shift from a retrospective to prospective memory code. The results are interpreted as support for a medial prefrontal cortex role in mediating a prospective code perhaps via knowledge systems based on temporal information. PMID- 2924833 TI - Suprarhinal cortex response to electrical stimulation of the lateral amygdala nucleus in the rat. AB - Electrical stimulation of the lateral amygdala nucleus was found to evoke field potentials and influence unitary activity in the suprarhinal cortex of anesthetized rats. Laminar distributions of the field responses consisted of positive waves in superficial layers, that reversed to electronegatives from a depth of 0.4-0.5 mm. This response was followed by a shallow electropositive wave deeper than 0.7-0.8 mm. Extracellularly recorded units were studied in the posterior agranular insular area of the suprarhinal cortex. The data revealed that stimulation of the lateral amygdala produced a train of small amplitude spikes in association with a negative slow potential. Furthermore, such stimulation invariably elicited an inhibition of the spontaneous firing of large amplitude spikes, in association with a positive slow potential. The onset of this inhibitory response always occurred at longer latency than the excitatory one. The small amplitude spikes may well represent the firing of inhibitory interneurons after lateral amygdala stimulation. The study suggests that a feed forward system of inhibition appears to be present in the connection between lateral amygdala and posterior agranular insular area of the suprarhinal cortex. PMID- 2924834 TI - Effects of fornix transection and cingulate cortical ablation on spatial memory in rhesus monkeys. AB - This study, together with a parallel study in rats (Markowska et al. 1988), attempted to relate the effects of hippocampal-system damage on similar tasks in both rats and monkeys. Not only were monkeys given a task (Experiment 1) which was of the sort usually used with rats, but in the companion study rats were given tasks (Experiment 2) like those usually used with monkeys. Experiment 1 examined the performance of rhesus monkeys with hippocampal-system damage on a spatial working memory task. Monkeys were trained preoperatively on delayed nonmatching-to-sample in a T-maze, placed into groups matched for their preoperative learning scores, and then received one of three treatments: 1) transection of the fornix; 2) ablation of the cingulate cortex; or 3) a sham operation. Monkeys with fornix transection were severely and significantly impaired, but monkeys with cingulate cortical ablations were not significantly impaired, relative to the controls. The results demonstrate that monkeys with fornix transection are severely impaired on a spatial working memory task requiring locomotion and, taken together with earlier work, suggest that the effect of fornix transection in both rodents and nonhuman primates is at least qualitatively similar (see Markowska et al. 1988). Experiment 2 assessed the role of the fornix and cingulate cortex in three conditional tasks in which the monkeys were provided with various spatial cues to indicate which one of two objects was rewarded. Both experimental groups were unimpaired, relative to the control group, on all three tasks, indicating that fornix transection does not produce a general impairment in place learning. PMID- 2924835 TI - A comparative analysis of the role of fornix and cingulate cortex in memory: rats. AB - In order to compare the role of the fornix (FX) and cingulate cortex (CC) in memory, rats were trained in a series of discriminations using procedures that were the same as those used for monkeys (Murray et al. 1986, 1988). A spatial delayed nonmatching-to-sample (DNMS) discrimination tested recent memory for spatial location in a T maze using interrun intervals (IRI) that varied from 5 s to 15 min. FX and CC lesions produced a substantial impairment in the performance of this task during postoperative testing. Three conditional discriminations (CD) followed. In each one, the rat was presented with two objects, only one of which was correct. The nature of the conditional stimuli changed in each discrimination: the place of the maze in the room; the direction that the rat moved to approach the objects; the side (left or right) to which the rat turned. Control rats learned all three types of conditional discriminations. FX and CC lesions did not impair choice accuracy. In a subsequent repetition of the spatial DNMS procedure, FX and CC lesions again produced a substantial impairment, indicating that the lack of an impairment in the three CDs was not due to recovery of function. These data indicate that the hippocampal system and its connections through the fornix are importantly involved in spatial working memory in both rats and monkeys, and that the CDs do not require this type of memory. The results are discussed in the context of different theories of the brain mechanisms involved in memory. PMID- 2924836 TI - Place memory and scene memory: effects of fornix transection in the monkey. AB - Five experiments examined the effects of fornix transection upon some spatial and visual learning tasks in monkeys (Macaca fascicularis). For each trial of each task, the monkey was brought to a test tray and allowed to choose between 2 objects on the tray. In different tasks, different cues were provided by the experimenter to guide the monkey's choices. In total 5 different tasks were run (Experiments 1 to 5) and the results showed that the effects of fornix transection varied markedly between tasks: the animals with fornix transection were severely impaired in experiments 1, 3 and 5 but learned normally in experiments 2 and 4. It is concluded that the results cannot be explained by the simple hypothesis of a deficit in place learning, since some forms of place learning are unimpaired by fornix transection. A better general hypothesis is that the memory disrupted by fornix transection is like a snapshot memory, which stores the spatial arrangement of items in a witnessed scene. PMID- 2924837 TI - Mechanical and electromyographic responses to stretch of the human anterior tibial muscle at different levels of contraction. AB - The EMG response and the mechanical response to 2 degree stretch of the human anterior tibial muscle was studied during contractions ranging from 0% to 80% of maximal voluntary contraction (MVC). The EMG response showed three distinct peaks M1, M2, and M3 with peak latencies of 59 ms, 86 ms, and 120 ms respectively. At low background torques M1 dominated while M2 and M3 were small or absent. M2 and M3 dominated above 40% of MVC and M2 in particular showed "automatic gain compensation", i.e. it constituted a - more or less - constant proportion of the background EMG for all contraction levels. The ratio between M1 amplitude and background EMG steadily decreased with contraction level. Even though the summed contributions of M1, M2, and M3 to some degree showed automatic gain compensation, this was not the case for the mechanical response to stretch. Between 0% and 30% of MVC the reflex mediated mechanical response increased approximately in proportion to the contraction level, but the reflex mediated mechanical response peaked at 40% of MVC and declined to zero at 80% of MVC. This discrepancy between EMG and mechanical response was explained by a simple model. The regression line between rectified and filtered tibialis anterior EMG and torque was used to predict the mechanical response from the EMG response. At increasing contraction levels the twitch elicited by supramaximal electrical stimulation decreases, and we reduced the predicted mechanical response by the same factor as the twitch.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2924838 TI - Note on the tonotopic organization in the cat medial geniculate body: influence of sampling of units. AB - The tonotopic organization observed in the present study for the pars lateralis (LV) of the medial geniculate body (MGB) in nitrous oxide anesthetized cats is generally consistent with that previously reported under barbiturate anesthesia. The present data, however, provide evidence for local deviations in characteristic frequency (CF) using appropriate sampling procedures of single units. Although the majority of pairs of units recorded simultaneously with the same microelectrode showed comparable CFs, a few pairs of such neighbouring units displayed CF disparities of up to 1.5 octaves. In addition, some units characterized by an elevated threshold had a CF deviating significantly from the general CF progression observed for the majority of units having low thresholds. This study points out the influence of the sampling procedure on the quality of the tonotopic organization observed in the MGB in addition to a possible effect of the level of anesthesia. PMID- 2924839 TI - Comparison of human infants and rhesus monkeys on Piaget's AB task: evidence for dependence on dorsolateral prefrontal cortex. AB - This paper reports evidence linking dorsolateral prefrontal cortex with one of the cognitive abilities that emerge between 7.5-12 months in the human infant. The task used was Piaget's Stage IV Object Permanence Test, known as AB (pronounced "A not B"). The AB task was administered (a) to human infants who were followed longitudinally and (b) to intact and operated adult rhesus monkeys with bilateral prefrontal and parietal lesions. Human infants displayed a clear developmental progression in AB performance, i.e., the length of delay required to elicit the AB error pattern increased from 2-5 s at 7.5-9 months to over 10 s at 12 months of age. Monkeys with bilateral ablations of dorsolateral prefrontal cortex performed on the AB task as did human infants of 7.5-9 months; i.e., they showed the AB error pattern at delays of 2-5 s and chance performance at 10 s. Unoperated and parietally operated monkeys succeeded at delays of 2, 5, and 10 s; as did 12 month old human infants. AB bears a striking resemblance to Delayed Response, the classic test for dorsolateral prefrontal function in the rhesus monkey, and indeed performance on AB and Delayed Response in the same animals in the present study was fully comparable. These findings provide direct evidence that AB performance depends upon dorsolateral prefrontal cortex in rhesus monkeys and indicates that maturation of dorsolateral prefrontal cortex may underlie the developmental improvement in AB performance of human infants from 7.5-12 months of age. This improvement marks the development of the ability to hold a goal in mind in the absence of external cues, and to use that remembered goal to guide behavior despite the pull of previous reinforcement to act otherwise. This confers flexibility and freedom to choose and control what one does. PMID- 2924840 TI - Postural synergies in axial movements: short and long-term adaptation. AB - Fast backward trunk movements are accompanied by hip, knee and ankle rotation which compensate for the backward shift of the center of gravity. The electromyographic pattern associated with the performance of these movements and the associated synergies consists of a fairly synchronous activation of the prime mover (erectores spinae) and the muscles situated at the back of the leg (hamstring, calf muscles). This pattern is called the "non anticipated pattern". The effect of training on the EMG pattern and on the subjects' mechanical performances was investigated by comparing a population of untrained subjects with one of highly trained gymnasts. A new EMG pattern was observed in the highly trained gymnasts, the "distally anticipated pattern" consisting of an early activation of the gastrocnemius, and in some subjects also of the hamstring, indicating that a long term adaptation had taken place. Performances expressed as a ratio between the displacement of the center of gravity projection onto the ground and the velocity of the movement were clearly better in the gymnasts. Short term adaptation was found to occur in the gymnasts and not in the untrained group when the movement was performed while standing on a narrow support. A suppression of the distal gastrocnemius burst occurred in the gymnasts from the first trial under the constrained standing condition whereas no change occurred in the untrained group. The flexibility of the EMG patterns associated with axial movements occurring either spontaneously or as a result of long or short term training is discussed. PMID- 2924841 TI - Olivary branching projections to the flocculus, nodulus and uvula in the rabbit. I. An electrophysiological study. AB - Olivocerebellar branching projections to the flocculus, nodulus and uvula were studied electrophysiologically in pigmented rabbits anesthetized with pentobarbital and halothane. Neurons in the dorsal cap of the inferior olive were antidromically activated by stimulation of the contralateral flocculus, nodulus and uvula. The antidromic responses in the dorsal cap from the flocculus, nodulus and uvula partially occluded with each other. Electrical stimulation of the nodulus (or uvula) evoked early and late climbing fiber responses in the flocculus with latencies of 4.0 ms and 10.0 ms, respectively. The early response was resistant to repetitive stimulation and not affected by interruption of the olivocerebellar fibers at the lower medulla, while the late response was abolished by these two procedures. This indicated that the early response was evoked through climbing fiber branches to the flocculus and nodulus (or uvula) as an axon reflex, while the late response was evoked via the inferior olive. Of 76 Purkinje cells in the flocculus, 35.6% showed climbing fiber activation through branches to the nodulus and/or uvula, 70% of which were orthodromically activated through climbing fibers from the contralateral optic tract. Electrical stimulation of the flocculus or uvula evoked the early and late climbing fiber responses in the nodulus. Of 60 Purkinje cells in the nodulus, 63.4% showed axon reflex activation from the flocculus and/or uvula, 42% of which were activated through climbing fibers from the contralateral optic tract. These findings demonstrated that the flocculus, nodulus and uvula receive branching climbing fiber projection from the inferior olive, a part of which conveys visual information. PMID- 2924843 TI - NGF treatment promotes development of basal forebrain tissue grafts in the anterior chamber of the eye. AB - The effects of nerve growth factor (NGF) on developing central cholinergic neurons were studied using intraocular grafts of rat fetal (E17) basal forebrain tissue. Prior to grafting, grafts were incubated in NGF or saline. Transplants were allowed to mature for six weeks, receiving weekly intraocular injections of NGF or saline. Measurements of NGF levels in oculo after one single injection showed that NGF slowly decreases in the anterior chamber fluid, and after one week, low but significant levels were still present in the eye. Following pretreatment with diisopropylfluorophosphate (DFP), the cholinergic neurons in the grafts were analyzed using three morphological markers: antibodies to cholineacetyltransferase (ChAT), antibodies to acetylcholinesterase (AChE Ab) and acetylcholinesterase histochemistry (AChE). The transplants grew well and became vascularized within the first week. The growth of the NGF-treated basal forebrain grafts was significantly enhanced as compared to the growth of the saline-treated grafts evaluated with repeated stereomicroscopical observations directly through the cornea of the ether-anaesthetized hosts. The NGF-treated grafts contained almost twice as many cholinergic neurons seen with all the cholinergic markers used, as the saline-treated grafts. However, there was no difference in cholinergic cell density between the two groups. The morphology and size of an individual cholinergic neuron was similar in the two groups. The fiber density as evaluated with AChE-immunohistochemistry did not change after NGF-treatment. The DFP-treatment did not seem to affect the AChE-immunoreactivity since an extensive fiber network was found, whereas almost no fibers were seen using conventional AChE histochemistry. We have demonstrated that in oculo transplantation of basal forebrain is a useful model for examining in vivo effects of NGF on central cholinergic function. The marked volume increase of NGF-treated grafts and the unchanged density of cholinergic cells and terminals suggests, that NGF increases the survival of not only developing cholinergic neurons, but possibly other non cholinergic neurons and non-neuronal cells as well. These results support the notion that NGF acts as a neurotrophic factor on cholinergic and possibly non cholinergic cells in the central nervous system. PMID- 2924842 TI - Effects of kainic acid lesions of the nucleus reticularis tegmenti pontis on fast and slow phases of vestibulo-ocular and optokinetic reflexes in the pigmented rat. AB - The nucleus reticularis tegmenti pontis (NRTP) and adjacent pontine reticular formation were lesioned chemically using the neurotoxic agent kainic acid, and the effects of these lesions on horizontal ocular optokinetic and vestibular nystagmus were examined. Eye position was measured in the alert, NRTP-lesioned animals with the electromagnetic search coil technique. Optokinetic and vestibular stimuli consisted of steps of rotations or sinusoidal oscillations of a fullfield visual pattern surrounding the animal or of the animal in total darkness, respectively. In a first group of animals, small unilateral NRTP lesions were produced by placing a single kainic acid injection in the area of the left NRTP. In one third of the animals, ipsilateral quick phases of optokinetic and vestibular nystagmus were abolished. In the remaining animals, quick phases were deficient to various degrees or not affected at all. There were no changes in the characteristics of optokinetic step responses to ipsilateral pattern rotations which activate predominantly optokinetic pathways on the side of the brainstem lesion. In animals with ipsiversive quick phase deficits, contralateral pattern rotations elicited tonic eye deviations. In a second group of animals, large uni- or bilateral lesions were produced by injecting kainic acid into three separate rostral, middle and caudal levels of the right NRTP. These animals had uni- or bilateral quick phase deficits during optokinetic and vestibular nystagmus. Optokinetic nystagmus in response to velocity steps of pattern rotation towards the lesion side was strongly reduced in gain even in those animals that had no apparent deficits in the fast contraversive reset phases. In four out of six animals, responses to sinusoidal optokinetic pattern oscillations were reduced in gain and showed increased phase lags compared to controls. Vestibulo-ocular responses to velocity steps of head rotations were of normal gain but reduced in duration (measured from onset of stimulation to reversal of nystagmus). Sinusoidal vestibulo-ocular responses evoked by head oscillations exhibited reduced gain values and strongly increased phase leads in the frequency range below 0.5 Hz. The vestibular time constant was found to be around 4.5 s in animals with NRTP lesions compared to about 7.5 s in control animals. The present results show that large kainic acid lesions of the NRTP (and adjacent area) do not abolish optokinetic eye movements in the rat, in contrast to what has been reported after electrolytic lesions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2924844 TI - Negative cortical DC shifts preceding and accompanying simple and complex sequential movements. AB - Negative cortical DC shifts preceding and accompanying the execution of four different motor tasks were analysed in 18 subjects (Ss): Repetitive flexions and extensions of the forefinger had to be performed either by the right (1) or the left (2) hand. This simple motor task was compared to a complex one in which flexions and extensions of forefinger and hand had to be alternated in a fixed sequence. The complex task had either to be performed by the right (3) or the left (4) hand. Thus, the four conditions differed in the side of the performing hand (right/left) and in task-complexity (simple/complex). After its voluntary initiation, each task had to be performed for at least a period of six seconds. A Bereitschaftspotential (BP) preceded the voluntary initiation of the movement. Task-performance was accompanied by a negative DC shift called a performance related negativity (N-P). Amplitudes of BP and N-P were compared by analysis of variance (ANOVA) using the factors "performing hand" (right/left) and "task complexity" (simple/complex). "Performing hand" had significant effects on N-BP and N-P in C3* and C4* (positioned over the primary motor cortex) but did not influence mid-central (Cz*), frontal (F3, Fz, and F4) or parietal (P3, Pz, P4) recordings. "Task-complexity" had significant effects on N-P in mid-central (Cz*, C1*, C2*) and parietal (P3, Pz) recordings with higher negativity for complex movements. Recordings in C3* and C4* did not vary with "task complexity".(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2924845 TI - Specific suppression of pentylenetetrazol-induced epileptiform discharges in CA3 neurons (hippocampal slice, guinea pig) by the organic calcium antagonists flunarizine and verapamil. AB - Antiepileptic actions of the organic calcium antagonists flunarizine (cinnarizine derivate) and verapamil (papaverin derivat) on pentylenetetrazol-induced epileptic bioelectric activity were tested in CA3 neurones of hippocampal slices. In all experiments both calcium antagonists reduced the amplitudes and/or durations of paroxysmal depolarizations as well as their rate of occurrence, when the bath concentrations of flunarizine or verapamil exceeded 20 mumol/l. When they were added to the bath solution before pentylenetetrazol application, recordings of the resting membrane potential, of the membrane resistance, of action potentials and of spontaneous as well as of evoked excitatory and inhibitory postsynaptic potentials gave no indication that the antiepileptic effects of these drugs are due to unspecific depressive actions on neuronal excitability or spread of excitation. PMID- 2924846 TI - Ontogeny of cholecystokinin-8 and glutamic acid decarboxylase in cerebral neocortex of macaque monkey. AB - Concentration of cholecystokinin-8 and the activity of glutamic acid decarboxylase were determined in the various cerebral cortical subdivisions of Japanese monkey (Macaca fuscata fuscata) at three different ages (embryonic 4 months, full-term and adult). The CCK-8 immunoreactive material extracted with 90% methanol from the cerebral cortex of the adult and foetal monkey were shown to be identical with synthetic cholecystokinin-8 by the criterion of co-elution on gel filtration chromatography (Sephadex G-50). The peptide concentration increased dramatically by about 30-80 fold (in terms of protein) and 17-28 fold (in terms of wet weight) between embryonic 4-month-old and full-term monkeys, while the level decreased 1/6-1/16 (protein) and 1/4-1/10 (wet weight) between full-term and adult monkeys. In adults, the highest levels of the peptide was observed in the association cortex, orbital prefrontal cortex and posterior parietal cortex. Glutamic acid decarboxylase activity, on the other hand, gradually increased about 4-10 fold (protein) between embryonic 4-month-old and adult animals and there was little variation in the increase rate among the cerebral subdivisions. In contrast to cholecystokinin-8, no reduction in the enzyme activity occurred between full-term and adult animals. The high level of cholecystokinin-8 in the embryonic period suggests that the peptide may participate in the regulation of the development of primate cerebral cortex. PMID- 2924847 TI - H1 horizontal cells of carp retina have different postsynaptic mechanisms to mediate short- versus long-wavelength visual signals. AB - Vertebrate photoreceptors release neurotransmitter substance(s) tonically in the dark and this release is curtailed by light. Recently, we have become increasingly aware of the possibility that short- and long-wavelength visual signals are mediated differently during the synaptic transmission to second-order retinal neurons. The experiment described here advances this notion further by demonstrating a postsynaptic difference. Treatment of the carp retina by dopamine reduced the gap-junctional coupling of horizontal cells, and we made use of this known effect to measure the input resistance (Rin) of H1-type horizontal cells. Flashes of light increased Rin. This increase, however, was found to be smaller with short wavelengths, even though the comparison was made when voltage responses were equal in amplitude. Often, Rin was even found to decrease at the blue end of spectrum. No single postsynaptic mechanism can account for any equal voltage Rin difference such as this. The synaptic spectral segregation thus revealed is probably subserved by a dual scheme wherein the transmitter from blue sensitive cone photoreceptors acts to decrease the membrane conductance of H1 cells whereas the synapses made by red- and green-sensitive cones are of a classical excitatory type. PMID- 2924848 TI - Characteristics of the tooth pulp-driven neurons in a functional column of the cat's somatosensory cortex (SI). AB - The columnar arrangement of tooth pulp-driven (TPD) neurons in the first somatosensory cortex (SI) was studied by single unit analysis in the cat anesthetized with nitrous oxide and halothane. Tactile sensitive neurons in the oral area of SI were arranged functionally in a columnar organization. About 32% of the recorded neurons also responded to tooth pulp stimulation. Thus, the TPD neurons located in area 3b seem to be multireceptive in sensory modality. About 80% of the TPD neurons were F-type which respond with a short latency to tooth pulp stimulation and receive input from a small number of teeth. When a microelectrode penetrated through a single vertical column, most of the F-type TPD neurons encountered received common input from one or two tooth pulps. However, when an electrode was inserted across more than one column, there was no common pulpal input to the TPD neurons encountered in a track. Thus, the TPD neurons in a single column had identical peripheral and pulpal receptive fields, and the same latency of responses to tooth pulp stimulation. These characteristics would support the hypothesis that TPD (presumed nociceptive) neurons are arranged in a vertical column and it may be inferred that the columnar organization of TPD neurons in SI plays an important role in the sensory discriminative aspects of pulpal pain. PMID- 2924849 TI - Binocular depth perception, visual acuity and visual fields in cats following neonatal section of the optic chiasm. AB - We studied the role of the transcallosal pathway in stereopsis by measuring binocular and monocular depth perception in two cats that had undergone section of the optic chiasm at the age of 21 d. To ensure that the surgery did not impair vision to the extent that depth perception could not be evaluated, visual acuity and visual fields were also measured. In both of the chiasm-sectioned animals the visual fields were reduced and the visual acuity was substantially lower than in normal cats, with a maximum of about 2 cyc deg-1. Binocular depth thresholds of the chiasm-sectioned cats were worse than those of the normal cat but were better than their own monocular thresholds. These results suggest that the chiasm sectioned animals were still able to use binocular cues to judge depth and indicate that the indirect pathway through the corpus callosum is sufficient to mediate binocular depth perception. PMID- 2924850 TI - Toxic effects of triethyldodecylammoniumbromide (TEA-C12) on myelinated nerve fibers and blood-nerve barrier in the mouse. AB - The blocking effect of triethyldodecylammoniumbromide (TEA-C12), applied locally to the sciatic nerve, was studied in 28 adult BDF1 mice. Clinical parameters, electrophysiological recordings of muscle action potentials evoked by stimulation at the sciatic notch, and morphological aspects are presented. Our results show that both the minimal blocking concentration and half the minimal blocking concentration induce flaccid paresis of the treated hind-limb. There was a complete, long-lasting nerve conduction block due to Wallerian degeneration of the myelinated nerve fibers. In contrast, pain sensation was abolished only on day 4 after application of the minimal blocking concentration, but was preserved during the rest of the time that nerve conduction block was observed. This correspond to the electron microscopic finding of preservation of unmyelinated nerve fibers. Recovery of nerve conduction was characterized electrophysiologically by occurrence of minute polyphasic regeneration potentials between day 18 and 21, clinically by advanced restitution of muscle force on day 64, and morphologically by nerve regeneration. TEA-C12 also induced a disturbance of the blood-nerve barrier, demonstrated using an intraperitoneally administered biotinylated IgG tracer in the endoneurial space. The morphological features of the acute axonal changes of the myelinated nerve fibers including the degeneration of the axonal mitochondria suggest that the neurotoxic effect of TEA C12 is possibly mediated by interference with the axonal energy supply. The selective affection of myelinated nerve fibers separates TEA-C12 from other neurotoxins that induce changes of the axonal microorganelles or complete Wallerian degeneration of myelinated and unmyelinated nerve fibers. The selectivity for myelinated nerve fibers and the supposed pathogenetic mechanism exhibit some similarities with the human polyneuropathy caused by acute arsenic acid intoxication. PMID- 2924852 TI - Asymmetric velocity and acceleration profiles of human arm movements. AB - Displacement, velocity, acceleration and jerk (change of acceleration with time) were analyzed for arm flexion movement over a wide range of movement amplitudes and speeds. Relative time to peak velocity or relative duration of acceleration, k, was approximately 0.5 for the movements with intermediate speed (about 0.5 s in movement time), i.e., symmetric velocity and acceleration profiles. For the slow and ballistic movements, k shifted towards values below and above 0.5, respectively creating asymmetric profiles. Consistent k-dependence of movement time, peak velocity, maximum acceleration and maximum deceleration were observed. "Jerk cost", the square of the magnitude of jerk integrated over the entire movement, was calculated for each movement. A dynamic optimization technique to minimize jerk cost under the constraint on jerk input was applied to interpret the results, assuming that a major goal of skilled movements was to produce optimally smooth movements. The constrained minimum-jerk model explained speed dependent asymmetry of the velocity and acceleration profiles. Jerk cost consumed by the movements with intermediate speed approximately satisfied minimum-cost criterion predicted by the model but was higher than the criterion for slow and ballistic movements. The results suggested that optimality criteria other than jerk cost also should be considered to predict movement profiles over the entire range of speeds. PMID- 2924851 TI - Distribution of corticospinal neurons with collaterals to the lower brain stem reticular formation in monkey (Macaca fascicularis). AB - An earlier retrograde double-labeling study in cat showed that up to 30% of the corticospinal neurons in the medial and anterior parts of the precruciate motor area represent branching neurons which project to both the spinal cord and the reticular formation of the lower brain stem. These neurons were found to be concentrated in the rostral portion of the motor cortex, from where axial and proximal limb movements can be elicited. In the present study the findings in the macaque monkey are reported. The fluorescent retrograde tracer DY was injected unilaterally in the spinal cord at C2 and the fluorescent tracer FB was injected ipsilaterally in the medial tegmentum of the medulla oblongata. In the contralateral hemisphere large numbers of single DY-labeled corticospinal neurons and single FB-labeled corticobulbar neurons were present. A substantial number of DY-FB double-labeled corticospinal neurons were also found, which must represent branching neurons projecting to both the spinal cord and the bulbar reticular formation. These neurons were present in: 1. The anterior portion of the "cingulate corticospinal area" in the lower bank of the cingulate sulcus; 2. The supplementary motor area (SMA); 3. The rostral part of precentral corticospinal area; 4. The upper portion of the precentral face representation area; 5. The caudal bank of the inferior limb of the arcuate sulcus; 6. The posterior part of the insula. In these areas 10% to 30% of the labeled neurons were double-labeled. The functional implications of the presence of branching corticospinal neurons in these areas is discussed. PMID- 2924853 TI - The effects of reverse monocular deprivation in monkeys. I. Psychophysical experiments. AB - Monkeys had one eye closed at about 30 days of age for 14, 30, 60, or 90 days, then opened, and the fellow eye closed for another 120 days. The animals then had at least 10 months of binocular visual experience before behavioral training and testing were begun. All subjects were used in a series of psychophysical investigations during the next two years. The results of the behavioral studies indicated that the initially deprived eyes (IDE) of the two monkeys that were subjected to initial deprivation periods of 14 or 30 days recovered normal or near-normal spatial contrast sensitivity. In contrast, the two animals which underwent longer periods of initial deprivation showed incomplete recovery, especially for high spatial frequency stimuli. All of the monkeys exhibited a reduction in spatial contrast sensitivity for their reverse deprived eyes (RDE); the earlier the onset of the reverse-deprivation procedures (i.e., the shorter the initial period of deprivation), the greater the deficit in the RDE's spatial contrast sensitivity. Measurements of temporal contrast sensitivity showed that all of the subjects' IDEs had normal or near-normal sensitivity levels. However, the reverse-deprivation procedures initiated at 90 days of age or earlier produced a frequency-dependent reduction in the RDE's temporal modulation sensitivity. The measures of increment-threshold spectral sensitivity revealed that only the RDE of the monkey that had the shortest initial deprivation period had an abnormal spectral sensitivity function. The results demonstrate that many of the severe behavioral deficits produced by early monocular form deprivation can be recovered via reverse-deprivation procedures. However, depending upon the length of the initial deprivation period and the age at which the reversal procedure is initiated, the second deprivation period can also adversely affect the functional capacity of the RDE. PMID- 2924854 TI - Interhemispheric transfer of visual learning in monkeys with intact optic chiasm. AB - The purpose of the present experiments was to investigate the role of the forebrain commissures in interhemispheric visual transfer when both eyes are open and the optic chiasm is intact. Cynomolgus monkeys (Macaca fascicularis) learned a series of two-choice simultaneous visual discriminations. The visual stimuli were bipartite, with independently determined left and right halves. If such a stimulus is fixated centrally, the two halves fall into opposite visual hemifields. After 10 trials of acquisition of each discrimination, the same discriminanda were presented for a further 10 trials in which, within each stimulus, the positions of the halves were exchanged: the left half became the right and vice versa. The unoperated animals transferred well to the altered stimuli, making many fewer errors than they made in learning the originally presented discrimination. In contrast, monkeys with section of the posterior corpus callosum and the anterior commissure transferred poorly. These effects show that the forebrain commissures are important for the interhemispheric transfer and integration of visual information in animals with a normal, intact peripheral visual system. PMID- 2924855 TI - Tuning properties of auditory cortex cells in the awake squirrel monkey. AB - Pure tone bursts elicited in primary auditory cortex (AI) cells of the awake squirrel monkey a wide range of response patterns which consisted of one or more excitatory or inhibitory temporal response components. In almost 60% of these cells, response patterns were frequency and/or intensity dependent. Response components such as early and late onset excitation, offset excitation and on-off excitation; as well as tonic excitation or inhibition often varied independently with changes in these stimulus parameters. Individual cells were therefore considered as multiple bandpass filters, and each discrete response component was analyzed separately for its tuning properties. A correlation between best frequencies of the various excitatory components (BEF), and between BEFs and best frequencies of inhibitory components (BIF), in cells which responded with more than one discrete response component, disclosed a significantly higher correlation between BEF/BIF pairs compared with BEF/BEF pairs, presumably reflecting certain "lateral inhibition like" processes. Applying Q10dB factor, and square root of Hf-square root of Lf bandwidth at 10 dB above threshold, as measures of the "sharpness" of response areas, revealed that approximately 65% of all response areas could be defined as "narrow" by either one of these 2 measures, with no distinction, in that regard, between excitatory and inhibitory components. The average response bandwidths of the narrowly and the broadly tuned components, at 10 dB above threshold, were 0.4 +/- 0.18 and 1.42 +/- 0.68 octaves respectively. A comparison with the medial geniculate body (MGB) of the squirrel monkey, applying the square root of Hf-square root of Lf measure of sharpness of tuning, showed a significantly higher proportion of narrow response areas in the AI. "Narrow" response areas in both these regions were equally narrow, whereas the "broad" response areas of MGB cells were significantly broader. These results suggest a sharpening of response areas throughout the geniculo-cortical transformation. PMID- 2924856 TI - Post-tetanic influences on primary afferent depolarization in the cat spinal cord. AB - In the spinal cord of pentobarbitone anaesthetised cats, increases in the electrical threshold of the terminations of extensor muscle group Ia afferent fibres, produced by tetanic stimulation of either the appropriate peripheral nerve or the central termination, were associated with parallel changes in the bicuculline-sensitive reduction in electrical threshold of the termination produced synaptically by impulses in flexor muscle low threshold afferent fibres (primary afferent depolarization, PAD) or by microelectrophoretic piperidine-4 sulphonic acid (P4S), an analogue of GABA. Since this post-tetanic hyperpolarization (PTH) could be produced by tetanic stimulation of a single termination centrally, and not by peripheral stimulation of heteronymous nerves, it presumably resulted from changes intrinsic to the tetanized termination. Increases in PAD and the effectiveness of P4S were probably associated with post tetanic activation of an electrogenic Na+/K+ pump as the predominant cause of PTH, whereas decreases may have been largely the consequence of post-tetanic increases in intracellular Ca2+ levels. These results provide further evidence that GABA is the depolarizing transmitter at axo-axonic synapses upon primary afferent terminals, and that the underlying membrane conductance increase has a reversal potential at a more depolarized level than the resting potential. PMID- 2924857 TI - Decrease in GABA immunoreactivity and alteration of GABA metabolism after kindling in the rat hippocampus. AB - The kindling model of epilepsy, induced by tetanic stimulation of Schaffer collateral/commisural fibers, was studied in the rat hippocampus. Gamma aminobutyric acid immunoreactivity was used to quantify the number of GABA immunoreactive somata per mm2 in CA1 region, 28 days after the last generalized seizure. Comparison of the numbers obtained from kindled animals with those from controls, showed a significant decrease (18%) on the ipsilateral stimulated side but none on the contralateral side. In control rats injection of the GABA transaminase inhibitor, amino oxyacetic acid (AOAA), led to a 46% increase in the number of cell somata immunoreactive for GABA. This probably results from an accumulation of GABA, reflecting GABA synthesis by glutamate decarboxylase (GAD) activity, in somata of interneurons that had initially a GABA content below the immunocytochemical detection threshold. In kindled rats, 31 days after the last seizure, the number of GABA-immunoreactive cells that could be observed after AOAA-treatment was significantly lower (35% ipsilateral and 25% contralateral) when compared to AOAA-treated controls. This suggests that in kindled animals a GAD dependent increase in GABA content did not take place in a subpopulation of interneurons. The observations for kindled rats are interpreted as a long-term decrease in GABA content and as an alteration in GABA turnover in a subpopulation of interneuron somata, the latter possibly due to a decrease in GAD activity. The long-term enhanced seizure sensitivity, characteristic for kindled animals, may be due to a decreased GABAergic inhibitory control of the neuronal circuitry in the CA1 region of the hippocampus. PMID- 2924858 TI - A study of corticospinal remodelling using retrograde fluorescent tracers in rats. AB - The retrogradely transported fluorescent tracers Fast Blue (FB) and Diamidino Yellow (DY) were injected into the spinal cord of adult rats that sustained unilateral frontoparietal cortical lesions at birth. Analysis of the resulting cortical labeling pattern in comparison to comparably injected control animals demonstrated an increase of retrogradely-labeled neurons within the unablated cerebral hemisphere ipsilateral to spinal cord injections. These ipsilateral labeled cells corresponded to previous descriptions, based on anterograde tracing techniques, of anomalous uncrossed corticospinal tract (CST) fibers. Additional findings indicated that the ipsilateral CST fibers are not axonal collaterals of normal, crossed CST fibers. Fluorescent tracer injections into cervical and lumbar spinal cord levels demonstrated a distribution pattern of labeled cells within the ipsilateral cortex that was similar to the topographic pattern found contralateral to spinal cord injections in normal animals. These findings support previous anatomical and electrophysiological data indicating that the neonatal cortical lesion-induced increase of ipsilateral CST fibers may be functional. PMID- 2924859 TI - Different anisotropies of movement direction in upper and lower layers of the cat's area 18 and their implications for global optic flow processing. AB - Cells in Area 18 of awake and behaving cats were tested for directional preference with a large visual noise pattern. Upper and lower layer cells were found to exhibit different anisotropies for movement direction, offset by 90 degrees. These findings could reflect different functions for the global mapping and processing of optic flow field in upper and lower layers. PMID- 2924860 TI - Electrophysiological evidence for the dendritic localization of a calcium conductance in guinea-pig substantia nigra neurones in vitro. AB - Within the substantia nigra, anatomical, neurochemical and pharmacological findings strongly suggest that transmitter and protein are secreted from the dendrites of nigrostriatal neurones. This phenomenon may underlie a non classical modulatory cellular mechanism. Two conductances are generated in nigrostriatal neurones independent of somatic action potentials, that might mediate this modulation. However, these conductances have never been directly nor precisely located specifically within the dendrites. The aim of this study was to record the membrane properties of substantia nigra zona compacta neurones in response to selective sectioning of the population of long 'apical' dendrites i.e. the removal of the zona reticulata. Intracellular recordings from substantia nigra zona compacta neurones were made from mesencephalic slices of the guinea-pig brain maintained in vitro. In cells without the apical dendrites, the membrane potential, input resistance and mean firing frequency was not significantly different from the control neurones. However, removal of the substantia nigra zona reticulata virtually abolished one conductance in particular. This conductance, seen in control neurones, is a long lasting slow depolarization which is resistant to tetrodotoxin blockade of sodium channels: rather, it is mediated by the entry of calcium ions and is optimally deinactivated at a hyperpolarised membrane potential. Hence, this study strongly suggests that this conductance is generated exclusively in the 'apical' dendrites. It has been postulated that this long lasting calcium conductance is central to the modulation of nigrostriatal neuronal excitability. Thus, the 'apical' dendrites could play a specific and active role in the functioning of nigrostriatal neurones. PMID- 2924862 TI - Length and width summation in human vision at different background levels. AB - The effect of background intensity on the spatial summation of rectangular stimuli of varying length and width was studied in human psychophysical experiments and compared with the known effects of light adaptation on the spatial summation of circular stimuli. Both the detection threshold and the threshold of orientation identification were measured. In agreement with previous data, summation was more efficient along the line stimulus than across it. This asymmetry was found to exist at all adaptation levels studied (1-1000 trolands). The adaptation level affected both length and width summation; the change in the length of summation was twice as great as the change in the diameter of summation with circular stimuli. Orientation selectivity was reduced for short lines presented on a dim background. The results suggest the existence of mechanisms of light adaptation at the level of cortical orientation-selective units. PMID- 2924861 TI - Function and structure of atypical muscle spindles after neonatal nerve crush in rats. AB - During the early postnatal period, the differentiation and maturation of muscle spindles in the rat is still dependent on their sensory innervation. When a nerve is crushed during this period, most spindles in the denervated muscles degenerate and after reinnervation only occasional spindles of atypical structure are to be found in these muscles. We determined the basic functional properties of these atypical spindles in adult rats and attempted to correlate them with their structural characteristics. The discharge rates of 13 afferent units from the soleus or lateral gastrocnemius muscles were evaluated in response to stretch. These units were capable of a slowly adapting response to 2-4 mm stretches. Their mean discharge frequencies at any point of the ramp-and-hold stretch were, however, on an average 50% lower than normal values. The conduction velocities of afferents from the atypical spindles were in the range of 10-40 m/s. Histological examinations revealed that 90% of the atypical muscle spindles found in the soleus or lateral gastrocnemius muscles had only 1 or 2 intrafusal fibres without any nuclear accumulations as compared to four intrafusal fibres in normal muscle spindles in the rat. The proportional decrease of the discharge rate in both the dynamic and static part of the response of these atypical spindles could be due to the decreased synaptic area between the sensory terminals and the intrafusal fibres and/or to altered structural properties of the intrafusal fibres. PMID- 2924864 TI - Significant differences in the retrograde labeling of spinothalamic tract cells by horseradish peroxidase and the fluorescent tracers fast blue and diamidino yellow. AB - The laminar distributions of spinothalamic tract cells retrogradely labeled by the fluorescent tracers Fast Blue and Diamidino Yellow and by free or lectin coupled horseradish peroxidase have been found to be significantly different. The total numbers of cells labeled by each method are similar, but nearly twice as many lamina I cells are labeled by the fluorescent tracers and more lamina V cells are labeled by peroxidase. Injection site spread and spurious labeling due to leakage or fibers of passage do not account for these differences. These results indicate that both horseradish peroxidase and fluorescent tracers may be selectively transported and, thus, that the cautious use of both methods should be recommended for analyses of afferent populations. PMID- 2924863 TI - Transplanted rat retinae do not project in a topographic fashion on the host tectum. AB - We report here that transplanted rat retinae do not project in a topographically organized fashion onto the host tectum. In fact, following the injection of two small non-overlapping regions of the host tectum, one with Fluorogold, the other with Rhodamine conjugated latex microspheres, groups of ganglion cells labelled with either dye are found interspersed throughout the ganglion cell layer of the retinal transplant. The absence of topography in the projections of transplanted retinae offers a new opportunity to examine the mechanisms which lead to topographically ordered projections in normal development. PMID- 2924865 TI - Development of NADPH diaphorase-positive pedunculopontine nucleus neurons. AB - Nicotinamide adenine dinucleotide phosphate (NAD-PH) diaphorase histochemistry was used to localize cholinergic neurons in the pedunculopontine nucleus of neonatal and adult rats. Measurements of cell body areas revealed an average area around 200 microns2 at birth, followed by a significant increase to approximately 500 microns2 by 2 weeks of age. Thereafter, there was a decrease in cell area such that by 5 weeks of age the neurons had attained their adult size of around 300 microns2. The marked increase in cell size at the end of 2 weeks of age is discussed in relation to significant events in the development of locomotor and other rhythmic function control systems. PMID- 2924866 TI - Decreased catecholamine content in parkinsonian adrenal medullae. AB - Autopsy specimens of adrenal medullae from parkinsonian and nonparkinsonian patients were analyzed for free catecholamines by high-performance liquid chromatography with electrochemical detection. The total free catecholamine content (nanomoles free catecholamine per milligram protein) was significantly lower in the parkinsonian patients than in the control population when the values were corrected for age and time from death to organ harvest. It is not established whether this decreased catecholamine content in the adrenals of parkinsonian patients is a concomitant of the disease itself or whether it is secondary to drug therapies used to treat the symptoms of Parkinson's disease. PMID- 2924867 TI - Synthesis of the major inducible heat shock protein in rat hippocampus after neonatal hypoxia-ischemia. AB - Rats aged 7 days were exposed to 3.5 h of cerebral hypoxia-ischemia produced by unilateral common carotid artery ligation combined with hypoxia (8% oxygen). The major inducible heat-shock protein, HSP-68, was synthesized in ipsilateral but not contralateral (control) hippocampus during early recovery (1 and 3 h). HSP-68 synthesis was not detected during longer recovery periods. The presence of HSP-68 was confirmed by Western blotting and immunostaining with a polyclonal antibody to HSP-68. PMID- 2924868 TI - Morphological alterations in dorsal root ganglion neurons after peripheral axon injury: association with changes in metabolism. AB - Axotomized rat sensory ganglion neurons have been shown to undergo rapid metabolic changes in the first 2 weeks after injury. The present study examined selected morphological features of these neurons over the same time period. Parameters studied included the position of the cell nucleus (eccentricity) and soma, nuclear, and nucleolar size over time periods primarily in the first 2 weeks after a unilateral crush injury of the sciatic nerve. Comparisons were made with normal ganglia and ganglia contralateral to the injury. The eccentricity of the nucleus in injured neurons was significantly altered within 1 day after injury and remained so over the entire time period studied. Alterations in neuron soma included an initial decrease in size at 1 day followed by a significant bilateral increase at 3 days after injury. Nuclear and nucleolar size changes were phasic with significant increases size peaking at 3-4 and 8-11 days after injury. These alterations coincided temporally with known changes in RNA synthesis occurring in these neurons after injury. Significant alterations in all parameters were observed on the uninjured side. Preliminary studies of the bilateral changes suggested that the trauma of the operation may be the major factor in this response. The data suggest that significant morphological alterations parallel the rapidly fluctuating change in neuronal metabolism after axon injury. PMID- 2924869 TI - Tissue sections from the mature rat brain and spinal cord as substrates for neurite outgrowth in vitro: extensive growth on gray matter but little growth on white matter. AB - The failure of axons to regenerate within the brain and spinal cord of mature mammals has been attributed to the absence of growth-promoting substances, especially extracellular matrix components, or to the presence of growth inhibiting substances, particularly components associated with CNS myelin. The ability of mature mammalian CNS tissue to support neurite regeneration was tested by growing explants of embryonic chick lumbar sympathetic ganglia on fresh frozen sections of the mature rat brain and spinal cord. The extent of neurite outgrowth was quantified using morphometric analysis for explants grown on sections that included most of the major anatomical divisions of the CNS. Extensive, but variable, regeneration was present on gray matter regions, whereas major white matter tracts showed poor support, if any, for neurite growth. The results are consistent with the presence of growth-inhibiting factors associated with CNS white matter but also indicate that most gray matter regions of the mature mammalian brain and spinal cord will support axonal regeneration in tissue culture in spite of the absence of known extracellular matrix components. PMID- 2924870 TI - Microinjections of D-Ala2-Met5-enkephalinamide placed into nucleus accumbens suppress hypothalamically elicited hissing in the cat. AB - The effects of D-Ala2-Met5-enkephalinamide (DAME) upon the hissing component of hypothalamically elicited affective defense behavior in the cat were examined in this study. Microinjections of DAME placed into the nucleus accumbens significantly suppressed this response in a dose and time dependent manner. This dose dependent suppression of affective defense decreased toward baseline levels at 60 and 90 min following delivery of 1 and 10 micrograms/0.5 microliters of DAME, respectively. Similar injections placed into the caudate nucleus had no effects upon this response. Neither vehicle control nor naloxone placed into nucleus accumbens was found to significantly alter latencies for hissing. Naloxone injected into nucleus accumbens prior to administration of either a 1 microgram or a 10-micrograms dose of DAME blocked the suppressive effects of DAME that were observed when this drug was administered alone. These findings suggest that opioid receptors in the nucleus accumbens play an important role in the regulation of the hissing component of hypothalamically elicited affective defense behavior in the cat. PMID- 2924871 TI - Neonatal adrenalectomy alters dendritic branching of hippocampal granule cells. AB - Alterations in glucocorticoid hormones are known to affect the development of brain and behavior, but the details of these effects at the cellular level are unclear. The present study was undertaken to determine whether dendritic growth and branching in glucocorticoid target neurons, the granule neurons of the hippocampal dentate gyrus, are affected by glucocorticoid hormones. Computerized morphometric analysis of Golgi impregnated granule cells showed that adrenalectomy on Postnatal Day 21 resulted in a small decrease in dendritic branching of lower order dendrites in both male and female rats at 42 days of age, while branching of distal dendrites was left unaffected. Conversely, dendritic branching in rats treated daily with hydrocortisone acetate (5 mg/kg) during the same period was not significantly different from that of untreated rats. Total dendritic length was unaffected by either treatment. These results suggest that relatively minor alterations may occur in the circuitry in the inner molecular layer of the dentate gyrus, a region involving intrahippocampal connections, in the absence of physiological levels of glucocorticoid hormones. Whether these effects are mediated via glucocorticoid hormone effects on the presynaptic afferent neurons or via granule cell metabolic pathways remains to be determined. The most surprising result, given the presence of glucocorticoid receptors in granule cells and the relatively dramatic effects of glucocorticoid manipulations on whole brain that have been reported, is that the effects of these manipulations on dendritic morphology are minimal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2924873 TI - Restriction of enhanced [2-14C]deoxyglucose utilization to rhinencephalic structures in immature amygdala-kindled rats. AB - Sixteen-day-old albino rat pups were kindled to varying degrees of seizure severity with amygdala stimulations spaced 15 to 20 min apart. Subsequently, each rat pup was injected (ip) with 10 microCi of [2-14C]-deoxyglucose, and received several additional kindled seizures at regular intervals throughout the following 80 min, at which time it was killed and processed for deoxyglucose autoradiography. Increased seizure severity was associated with correspondingly increased deoxyglucose utilization in many rhinencephalic limbic structures. However, unlike adults, rat pups did not show discernibly increased neocortical, thalamic, or substantia nigra utilization. We postulate that the apparent confinement of seizure activity to limbic structures in pups is related to their relative lack of postictal seizure refractoriness, as well as to other indices of increased seizure susceptibility in immature animals. PMID- 2924872 TI - The threshold concentration of dietary ethanol necessary to produce toxic effects on hippocampal cells and synapses in the mouse. AB - A nutritionally complete liquid diet containing 0, 3, 5, or 7% ethanol was fed to C57 mice for 4 months and killed after a further 4 months on a standard food pellet diet. The number of pyramidal cells in Araldite sections of the hippocampus was not significantly reduced in any group relative to the zero alcohol intake group. Synaptic counts in the area occupied by the pyramidal cell basal dendrites showed the 7% alcohol group to have a reduced number of synaptic contacts, with no convincing differences between the other groups relative to the zero alcohol group. All measurements made collectively could not be used to distinguish 3 or 5% ethanol consuming animals from 0% ethanol consuming animals. Significant differences in body weight and dry brain weight were detected in the comparison of the group treated with 7% ethanol and 4-month recovery with the group receiving the 0% ethanol dose and 4-month recovery. It is concluded that maintaining mice on a diet containing not more than 5% ethanol has no adverse long-term structural effects on hippocampal pyramidal cells or synapses. PMID- 2924874 TI - Effects of unilateral microinjections of GABAergic drugs into the inferior colliculus on auditory evoked potentials and on audiogenic seizure susceptibility. AB - Alteration of GABAergic neurotransmission within the inferior colliculus (IC) appears to be involved in the generation of the audiogenic seizure (AGS) susceptibility. In the present study, we provide evidence indicating that this susceptibility may result from IC neuronal hyperexcitability to sound induced by a decreased GABAergic inhibition. In a first experiment, a unilateral microinjection of bicuculline, a GABAa antagonist, into the IC of normal rats increased the amplitude of the collicular auditory evoked potential, while the microinjection of THIP, a GABAa agonist, decreased this response. In a second experiment, a unilateral microinjection of bicuculline into the IC induced AGS susceptibility in normal rats. PMID- 2924875 TI - Spinal cord localization and characterization of the neurons which give rise to the accessory phrenic nerve in the adult rat. AB - This study describes the spinal cord location and morphology of the neurons which give rise to the accessory phrenic nerve in the rat. The results indicate that the cell bodies of the accessory phrenic nerve are a caudal extension of the phrenic nucleus. These cell bodies are located from cervical spinal cord levels C5 to upper C6 and comprise approximately 11% of the total phrenic motoneuron pool. The substantial phrenic contribution indicates the importance of the accessory phrenic nerve in both experimental and clinical manipulations of diaphragm innervation. PMID- 2924876 TI - Coexistent Hoffmann reflexes in human leg muscles are commonly due to volume conduction. PMID- 2924877 TI - Leishmania amazonensis: uptake and hydrolysis of 3H-amino acid methyl esters by isolated amastigotes. AB - Intracellular and isolated amastigotes of Leishmania amazonensis can be destroyed by L-amino acid methyl esters known to disrupt mammalian lysosomes. To evaluate the mechanism(s) involved in the leishmanicidal activity, we examined the uptake and hydrolysis of tritiated esters by isolated amastigotes. After incubation with the labeled compounds, parasites were recovered, were washed on filters, and their radioactivity was determined. Alternatively, amastigotes were separated from the medium by centrifugation through oil, and the radioactivity associated with free or esterified amino acids was measured after thin-layer chromatography. The results showed that the methyl esters of Trp, Leu, and Met, which are leishmanicidal, accumulated in and were rapidly hydrolysed by the amastigotes. [3H]Leu derived from [3H]Leu-OMe remained associated with the amastigotes even after a 1-hr chase in label-free medium, but the ester species was rapidly lost upon washing of the parasites. In contrast, the esters of Ile and Ala, which are not leishmanicidal, were only slowly hydrolysed, and most of the radioactivity was lost upon washing. We have previously shown that certain amino acid esters and weak bases protect Leishmania from damage by leucine methyl ester (Leu-OMe). In the present experiments, these compounds reduced, in concentration-dependent fashion, the hydrolysis of [3H]Leu-OMe and the accumulation of [3H]Leu in the amastigotes. Overall, the results indicate that, as in lysosomal disruption, leishmanicidal activity is associated with ester hydrolysis and amino acid accumulation in the parasites. The nature and location of the parasite esterolytic enzymes requires additional investigation. PMID- 2924878 TI - Leishmania major: histopathological responses before and after topical treatment in experimental animals. AB - The cellular response in the cutaneous leishmaniasis lesion (CL), of BALB/c mice treated topically with an ointment composed of 15% paromomycin and 12% methylbenzethonium chloride (PR-ointment) was studied. In the infected, untreated control group, the lesion showed progressive necrosis with an increase in the number of parasites, macrophages, lymphocytes, and polymorphonuclear cells over a period of 18 weeks. In the PR ointment-treated group, complete healing of the lesion was observed 4 weeks after termination of treatment, but total elimination of the parasites from the lesion was observed only 2 weeks later. A marked reduction in the number of macrophages and polymorphonuclear cells was observed during the healing process. A similar phenomenon was observed with mice inoculated intraperitoneally with paromomycin alone, although total elimination of the parasites from the lesions of these mice was not demonstrated over a period of 18 weeks. Neither L3T4 helper T cells nor Ly2 cytotoxic suppressor T cells were detected in the CL lesion, either before or after treatment. PMID- 2924879 TI - Schistosoma mansoni: pairing of male worms with artificial surrogate females. AB - To determine whether male worms provide any specific polypeptides to females, we produced extruded alginate fibers that resembled the size and shape of mature female worms. Males clasped these surrogate "female worms" and remained "paired" with them for long periods. On polyacrylamide gel electrophoresis, fibers clasped for several days showed bands at approximately 40 and 46 kDa which were never found in fibers incubated in the same medium but not clasped by males. We believe that these may be substances transferred from male worms during normal pairing. Males biosynthetically labeled with [14C]leucine were permitted to pair with fibers, which took up a broad range of polypeptides visualized on long autoradiographic exposure to gels. PMID- 2924880 TI - Cerebrovascular autoregulation is resistant to calcium channel blockade with nimodipine. AB - In normal baboons cerebrovascular resistance changed along with blood pressure to maintain blood flow constant. This 'autoregulation' was not significantly altered in animals treated with a dose of the calcium channel blocker nimodipine causing selective cerebral vasodilation. PMID- 2924881 TI - Schistosoma mansoni: onset of chemoattraction in developing worms. AB - Heterosexual chemoattraction studies on juvenile worms showed that 20- and 21-day old worms do not attract each other, whereas 23- and 28-day-old worms are attracted to each other and pair with worms of the opposite sex. This onset of chemoattraction in vitro corresponds to the time when worms begin pairing in vivo. The ability of single worms to locate each other and mate is presumably mediated by chemoreceptors. PMID- 2924882 TI - Differences in chromosome A arrangement between Drosophila madeirensis and Drosophila subobscura. AB - The proximal half of the A (= X) chromosome of D. madeirensis has a gene arrangement very similar to the A1 or A6 inversions found in D. subobscura. Polytene chromosome analysis of hybrids between D. madeirensis and strains of D. subobscura homozygous for such inversions shows, however, that D. madeirensis has a gene arrangement different from any known for D. subobscura. These results provide evidence for a greater differentiation of the X chromosome in these species than has previously been described; it seems that the X chromosome is the only one that has undergone structural variation during the speciation process. PMID- 2924883 TI - Single amino acid substitutions in sn-glycerol-3-phosphate dehydrogenase allozymes from Drosophila virilis. AB - The amino acid sequence was compared among the three allelic variants (allozymes) of sn-glycerol-3-phosphate dehydrogenase in D. virilis, which are detected by one dimensional electrophoresis. The alpha GPDHf variant was different from the alpha GPDHm by only one substitution of 68-lysine for asparagine; alpha GPDHs differed from alpha GPDHm by substitution of 127-glycine for arginine. No electrophoretically 'silent' substitutions were found in a total of 352 amino acid residues. PMID- 2924884 TI - 21st annual meeting of the Swiss Societies for Experimental Biology (USGEB/USSBE). March 30/31, 1989. Fribourg. Abstracts. PMID- 2924885 TI - Intermediate-dose (25 mg/m2) intravenous melphalan for patients with multiple myeloma in relapse or refractory to standard treatment. AB - Intermediate-dose (25 mg/m2) intravenous melphalan has been evaluated in 34 multiple myeloma patients refractory to standard chemotherapies. The median time from diagnosis to entering of patients into the study was 27 months (range 7-71 months). A response was obtained in 12/34 patients (35%). 4 of 12 responding patients have relapsed and 2 of these have died; 8 responders have not relapsed and are still alive. The median duration of survival after 28 months of follow-up has not yet been reached in the group of patients responding to treatment. However, the overall median duration of survival for the 34 patients entered into the study was 8 months. The median duration of response was 16 months. Toxicity was limited to leukopenia, thrombocytopenia, nausea and vomiting. This lack of severe toxicity allowed us to administer the drug on an outpatient basis. The response rate and the low toxicity observed in this group of patients are encouraging and suggest that intermediate-dose intravenous melphalan is an effective and safe second line treatment for patients with multiple myeloma not responding to conventional treatment. PMID- 2924886 TI - Translocation (1;5)(q23;q33) in adult acute non-lymphocytic leukemia. AB - Chromosome banding studies carried out on bone marrow cells from a 57-year-old white caucasian male with an M1 acute non-lymphocytic leukemia (ANLL) revealed an unbalanced translocation involving chromosomes 1 and 5 [der(5)t(1;5)(q23;q33)] as part of complex abnormalities in 76% of the cells analyzed. This chromosomal abnormality is the first to be reported in an adult patient with acute non lymphocytic leukemia. A review of previous reports on translocations involving the juxtaposition of the 1q23----qter DNA segment to other chromosomes suggests that this new translocation may be specifically involved with abnormal myeloid proliferation. PMID- 2924887 TI - The splenomegaly of myeloproliferative disorders: effects on blood volume and red blood count. AB - By means of a scintigraphic method for estimation of spleen size, the relationship was studied between spleen size and anaemia, total blood volume and red cell volume in patients with myeloproliferative disorders. There was significant correlation between spleen size and Hb, RBC and PCV in myelofibrosis. The size of the enlarged spleen did not, however, correlate with the degree of anaemia in the leukaemias. There was positive correlation between spleen size and red cell volume in these conditions. It was not possible to evaluate the severity of polycythaemia from spleen size and the degree of enlargement of the spleen does not appear to be a reliable parameter for staging and deciding on treatment in patients with PPP. PMID- 2924888 TI - Reevaluation of the prognostic factors for splenectomy in chronic idiopathic thrombocytopenic purpura (ITP): a report on 181 cases. AB - From 1973 to 1986 we splenectomized 181 patients with chronic ITP after platelet kinetic studies with 51Cr or 111In. Mean age at diagnosis was 34 (range 4-79 yr). Follow-up of at least 1 yr after splenectomy was available in every patient. 141 patients (78%) achieved remission (platelets greater than 100 x 10(9)/l by 3 months after splenectomy), of whom 9 subsequently relapsed. Among the 40 non responders at 3 months, 3 achieved a later remission spontaneously. Factors associated with response to splenectomy included a high post-operative platelet count (p = 0.0001), younger age at the time of surgery (p = 0.0077) and predominantly splenic sequestration of platelets (p = 0.0002), the two latter factors being partially correlated. In a multivariate analysis, however, only post-operative platelet count and age retained an independent prognostic significance, whereas the sequestration site of platelets had only borderline value. These results are discussed in the context of indications of platelet kinetic studies in chronic ITP, before splenectomy is considered. PMID- 2924889 TI - Treatment of multiple myeloma with carboquone-prednisolone. AB - 18 previously untreated patients with multiple myeloma were entered in a clinical study of a combination chemotherapy, carboquone (CQ) and prednisolone (P) (CQ-P). Response was observed in 44% of patients treated with CQ-P judged by the criteria for response to chemotherapy. The median survival time was 33 months. Serious toxic reactions seldom occurred. The results suggest that the combination of CQ-P has efficacy in the treatment of multiple myeloma and could have a role among primary chemotherapeutic regimens for the disease. Further clinical trials should be conducted to establish a new drug combination in which CQ is included. PMID- 2924890 TI - Isolation and characterization of a tumor necrosis factor binding protein from urine. AB - Tumor necrosis factor (TNF)/cachectin can produce both beneficial and harmful manifestations. Mechanisms may operate to counteract potentially harmful effects such as shock and cachexia. The TNF binding protein (TNF-BP), which is found at increased levels in serum and urine of patients with chronic renal failure, may play such a role. TNF-BP was purified 1,000,000-fold to homogeneity from urine of patients with chronic renal failure by use of ion exchange chromatography, affinity chromatography on TNF-Sepharose and reverse phase chromatography. The purified protein contained only one chain with an apparent Mr on sodium dodecyl sulfate-polyacrylamide gel electrophoresis of 30,000. The aminoterminal amino acid sequence D-S-V-X-P-Q-G-K-Y-I-H-P-Q-V-N-S-I-X-K-T revealed no significant homologies with previously described protein sequences. TNF-BP may act as a regulator of the bioactivities of TNF/cachectin. PMID- 2924891 TI - Acute transformation of chronic myelomonocytic leukaemia: a multivariate study of predictive factors. AB - In an attempt to determine the possible predictive value of the main clinical and haematological initial features of chronic myelomonocytic leukaemia (CMML) on the evolution to acute leukaemia, as well as the real impact of such an event on survival, 35 such patients were submitted to multiple regression analyses. At the time of the study 30 out of the 35 patients had died, with a median survival of 8.2 months for the whole series. 12 patients (34%) developed acute leukaemia, between 1.5 and 42.1 months from diagnosis of CMML, the actuarial median time of acute transformation being 29.4 months. The initial bone marrow blast cell percentage was the only factor influencing the development of acute leukaemia. On the other hand, the multivariate survival study showed that acute transformation introduced in the model as a time-dependent variable had a clear-cut unfavourable influence on the outcome of CMML patients, as did palpable spleen, advanced age and marked monocytosis. PMID- 2924893 TI - Relation between occupational exposure to organic solvents and chromosome aberrations in non-Hodgkin's lymphoma. AB - Chromosome analysis of lymphoma cells was performed in 54 untreated patients with non-Hodgkin's lymphoma (NHL). 10 patients had a history of daily occupational handling of organic solvents for at least 1 year (exposed group) and 44 patients had never (or only for shorter periods) worked with solvents (unexposed group). There were no differences between exposed and unexposed patients regarding age, clinical stage or histologic malignancy grade. The patients were assigned to three categories: Patients with 0-4, 5-9, or greater than or equal to 10 cytogenetic events producing clonal aberrations of the lymphoma cells. The proportions of exposed patients in these categories were 2/26 (8%), 5/20 (25%) and 3/8 (38%); respectively, i.e. with increasing numbers of events there was an increasing probability of previous exposure to solvents (p = 0.035, trend analysis). 5 of 7 exposed patients (71%) with intermediate or high-grade lymphomas displayed translocations involving the band 14q32. Such 14q+ markers were found in only 5 out of 28 unexposed patients (18%) with lymphomas of comparable malignancy grade (p = 0.01). Among unexposed patients with intermediate or high-grade lymphoma the most common clonal aberration was 6q- which occurred in 10 out of 28 patients (36%). This abnormality was not observed in the exposed patients with lymphomas of corresponding malignancy grades (p = 0.08). It thus appears that the number of clonal chromosome aberrations is especially large in NHL patients with a history of occupational exposure to organic solvents. Moreover, such exposure may be associated with characteristic cytogenetic changes in the lymphoma cells. PMID- 2924892 TI - Sialyltransferase activity and sialic acid levels in multiple myeloma and monoclonal gammopathy. AB - A significant elevation of peripheral blood mononuclear cell sialyltransferase activity (STA) was observed in 14 patients with multiple myeloma (MM), and compared to 7 patients with monoclonal gammopathy of undetermined significance (MGUS) and to 10 controls. Serum sialyltransferase was significant higher in MM patients as compared to controls. It was also higher than in MGUS patients, but the difference here was not statistically significant. STA was also determined in mononuclear bone marrow cells of 5 patients with MM (with 50 to 100% plasma cells in the bone marrow aspirate) and found to be 19 times higher than that of bone marrow mononuclear cells from 6 patients with non-malignant disorders (with less than 1% plasma cells in the bone marrow aspirate). No significant differences were observed in peripheral blood mononuclear cell sialic acid levels between MM, MGUS and controls. PMID- 2924894 TI - Comparative evaluation of normal human hematopoietic progenitors in adult blood, cord blood and bone marrow. PMID- 2924895 TI - Erythropoiesis of complement-sensitive cells in a PNH patients with iron deficiency anemia during iron therapy. PMID- 2924896 TI - Macroscopic hematuria in a hemoglobin-S heterozygote with a concomitant chromosome with triple alpha loci: a possible pathophysiologic mechanism. PMID- 2924897 TI - CSF fibronectin in Burkitt's lymphoma: an early marker for CNS involvement. PMID- 2924898 TI - Simultaneous presentation of relapsing non-Hodgkin's lymphoma and Hodgkin's disease. PMID- 2924899 TI - Distribution of HLA genotypes in sibs of patients with acute lymphoblastic leukemia. PMID- 2924900 TI - Soluble, nitrate/nitrite-inducible cytochrome P-450 of the fungus, Fusarium oxysporum. AB - Both soluble and microsomal fractions of Fusarium oxysporum contain cytochrome P 450(P-450). We report here that the P-450 in the soluble fraction was induced only when nitrate or nitrite was added to the growth medium, whereas the microsomal P-450 was synthesized regardless of the medium compositions. The reduced-CO complex of the soluble P-450 exhibited an absorption spectrum that is different from that of the microsomal counterpart. These results indicate that the soluble P-450 is distinct from the microsomal species and suggest a novel function for the former P-450. PMID- 2924901 TI - Halobacterial flagellins are encoded by a multigene family. Identification of all five gene products. AB - Flagellins of Halobacterium halobium are encoded in five different but homologous genes. Flagellins isolated from purified flagella were digested and the resulting peptides sequenced. The amino acid sequence data obtained prove that all five gene products are expressed and integrated into the flagellar bundle. PMID- 2924902 TI - Identification of a neurite outgrowth-promoting domain of laminin using synthetic peptides. AB - We have identified a synthetic peptide derived from the B2-chain of mouse laminin, Arg-Asn-Ile-Ala-Glu-Ile-Ile-Lys-Asp-Ile (p20), which stimulates the neurite outgrowth-promoting activity of the native molecule. In organotypic cultures, neurons from newborn mouse brain or embryonic peripheral nervous system responded by extensive neurite outgrowth for native laminin or the peptide p20 in the culture medium. If rat cerebellar neurons were grown on laminin, 1-5 microM (1-5 micrograms/ml) of peptide p20 in the culture medium competed with laminin and inhibited neuronal attachment and neurite outgrowth, whereas higher concentrations (greater than 50 microM; greater than 50 micrograms/ml) had a specific neurotoxic effect. When peptide p20 was used as the culture substratum, neurite outgrowth in cerebellar cultures was up to 60% of that seen on native laminin. Our results indicate that a neurite outgrowth-promoting domain of laminin is located in the alpha-helical region of the B2-chain, and is active for both central and peripheral neurons. PMID- 2924903 TI - Comparison of partial amino acid sequences of two protamine 2 variants from stallion sperm. Structural evidence that the variants are products of different genes. AB - Protamine 1 and two protamine 2 variants were isolated from stallion sperm and separated by acetic acid-urea gel electrophoresis. After electroblotting onto polyvinyldifluoride filters, their amino-terminal amino acid sequences were determined by pulse-liquid peptide sequencing. The sequences of the two protamine 2 variants are homologous but slightly different in length and amino acid composition and indicate for the first time the existence of two different genes for this protamine species. PMID- 2924904 TI - Evidence for two closely related isozymes of arylamine N-acetyltransferase in human liver. AB - Acetyl CoA-dependent arylamine N-acetyltransferase (EC 2.3.1.5) is the target of a genetic polymorphism in the metabolism of drugs and carcinogens. N Acetyltransferase was purified 1000-fold from cytosol of human liver and its identity was verified by amino acid sequence homology of two of its tryptic peptides with published rabbit and chicken N-acetyltransferase sequences. Enzyme activity correlated with the presence of two proteins, NAT-1 and NAT-2, with indistinguishable molecular masses (31 kDa). NAT-1 and NAT-2 could be separated by anion-exchange chromatography and were functionally distinguished by their different apparent affinities for the acceptor amine sulfamethazine (SMZ). Antibodies raised against NAT-1 were able to recognize both isozymes on Western blots. PMID- 2924905 TI - Weak interaction of spectrin with phosphatidylcholine-phosphatidylserine multilayers: a 2H and 31P NMR study. AB - Spectrin from human erythrocytes binds to bilayer dispersions of both DMPC and DMPS:DMPC (1:1, w/w). However, no effect of bound spectrin on the conformation of the lipid head groups, as measured from the deuterium quadrupolar splittings of DMPC or DMPS specifically deuterated in the polar head groups, was detected in 1:1 mixtures of the two lipids containing either deuterated DMPC or DMPS. Neither the phase transition of the DMPS:DMPC mixtures, nor the spin-lattice relaxation time (T1) of the deuterated DMPS head group, was affected by spectrin. These results argue against any strong interaction of spectrin with phosphatidylserine and rule out the possibility that spectrin is responsible for the maintenance of PS in the inner monolayer of the erythrocyte membrane during the whole life-span of this cell. PMID- 2924906 TI - Competition between Li+ and Mg2+ for ATP in human erythrocytes. A 31P NMR and optical spectroscopy study. AB - We have investigated the influence of Li+ on free intracellular Mg2+ concentration in human erythrocytes by 31P NMR and optical absorbance spectroscopies. In red cells loaded with 3 mM intracellular Li+, the chemical shift separation between the alpha- and beta-phosphate resonances of MgATP2- was approx. 0.9 ppm larger than that observed in Li+-free red cells. By analyzing the interaction of each red cell component with Mg2+ and Li+, we found that Mg2+ is displaced in part from MgATP2- upon addition of Li+ and that the released Mg2+ is bound to the red cell membrane causing an overall decrease in free intracellular Mg2+ concentration. PMID- 2924907 TI - The enzymes of the classical pentose phosphate pathway display differential activities in procyclic and bloodstream forms of Trypanosoma brucei. AB - The specific activities of each of the enzymes of the classical pentose phosphate pathway have been determined in both cultured procyclic and bloodstream forms of Trypanosoma brucei. Both forms contained glucose-6-phosphate dehydrogenase (EC 1.1.1.49), 6-phosphogluconolactonase (EC 3.1.1.31), 6-phosphogluconate dehydrogenase (EC 1.1.1.44), ribose-5-phosphate isomerase (EC 5.3.1.6) and transaldolase (EC 2.2.1.2). However, ribulose-5-phosphate 3'-epimerase (EC 5.1.3.1) and transketolase (EC 2.2.1.1) activities were detectable only in procyclic forms. These results clearly demonstrate that both forms of T. brucei can metabolize glucose via the oxidative segment of the classical pentose phosphate pathway in order to produce D-ribose-5-phosphate for the synthesis of nucleic acids and reduced NADP for other synthetic reactions. However, only procyclic forms are capable of using the non-oxidative segment of the classical pentose phosphate pathway to cycle carbon between pentose and hexose phosphates in order to produce D-glyceraldehyde 3-phosphate as a net product of the pathway. Both forms lack the key gluconeogenic enzyme, fructose-bisphosphatase (EC 3.1.3.11). Consequently, neither form should be able to engage in gluconeogenesis nor should procyclic forms be able to return any of the glyceraldehyde 3 phosphate produced in the pentose phosphate pathway to glucose 6-phosphate. This last specific metabolic arrangement and the restriction of all but the terminal steps of glycolysis to the glycosome may be the observations required to explain the presence of distinct cytosolic and glycosomal isoenzymes of glyceraldehyde-3 phosphate dehydrogenase and phosphoglycerate kinase. These same observations also may provide the basis for explaining the presence of cytosolic hexokinase and phosphoglucose isomerase without the presence of any cytosolic phosphofructokinase activity. The key enzymes of the Entner-Doudoroff pathway, 6 phosphogluconate dehydratase (EC 4.2.1.12) and 2-keto-3-deoxy-6-phosphogluconate aldolase (EC 4.1.2.14) were not detected in either procyclic or bloodstream forms of T. brucei. PMID- 2924909 TI - Influenza neuraminidase is delivered directly to the apical surface of MDCK cell monolayers. AB - The aim of this study was to investigate whether influenza neuraminidase travels directly from the Golgi complex to the apical domain of the plasma membrane in virally infected epithelial (MDCK) cell monolayers, or whether it passes transiently through the basolateral domain. Using a new assay for the delivery of neuraminidase to the plasma membrane, we found that the time course of transport of this protein from the Golgi complex to the apical surface of MDCK cell monolayers was very similar to that for influenza haemagglutinin, which is known to be delivered directly to its destination. In addition, a similar time course of neuraminidase transport was found in BHK cells, which are not asymmetric and in which delivery must therefore be direct. Finally, basolateral exposure of MDCK cell monolayers grown on nitrocellulose filters to an anti-neuraminidase antibody was shown to have no effect on the delivery of active neuraminidase to the apical surface. We conclude from these results that neuraminidase, like haemagglutinin, is delivered directly to the apical surface. PMID- 2924908 TI - Parallel stranded DNA with AT base pairing. AB - The concentration and temperature dependences of the UV and CD spectra of the oligonucleotide 3'-d(ApTpApTpApTpApTpApTp)-O(CH2)6O-5'-d(pApTpApTpApTpApT pApT) (eicosamer) in aqueous solution at pH 7 in the presence of 0.5 M NaCl were studied. At less than 10(-6) M, the eicosamer was shown to form in solution a hairpin with parallel orientation of chains (parallel hairpin). From thermal denaturation profiles [A260(T)] the thermodynamic parameters, delta H degrees, delta S degrees and Tm for parallel hairpin formation were calculated to be -90 +/- 8 kJ/mol. -300 +/- 20 J.mol-1.K-1 and 40.5 degrees C, respectively. The CD spectra of the parallel double helix differed from those of B-form DNA and had characteristic features: decreasing magnitude of the positive maximum at 265 nm and a negative peak at 285 nm. PMID- 2924910 TI - Enhanced levels of cathepsin B mRNA in murine tumors. AB - Relative amounts of mRNA for cathepsin B were measured in normal murine liver and three murine tumors, an invasive liver tumor (hepatoma, Hepa cl 9) and two melanoma variants (B16-F1 and B16 amelanotic melanoma, B16a). Using a human cDNA to the cathepsin B coding region as a hybridization probe, we detected two species of cathepsin B specific RNA transcripts (2.2 and 4.1 kb) in total RNA preparations of all four tissues. The concentrations of the 2.2 and 4.1 kb species were 3.6 and 2.7-fold greater in the highly metastatic B16a melanoma than in normal liver. The concentration of the 2.2 kb species in the invasive hepatoma was 1.7-fold greater than in normal liver. The increased levels of the 2.2 kb message were reflected in increases in activity of cathepsin B in both Hepa cl 9 and B16a. PMID- 2924911 TI - Genetic transformation of mouse cultured cells with the help of high-velocity mechanical DNA injection. AB - NIH 3T3 mouse cells were transfected by the plasmid pSV3neo (G418-resistant) with the help of high-velocity mechanical DNA injection based on the principle of bombarding cells with tungsten particles covered with the DNA. Stable transformants were obtained. Dot-hybridization and Southern analysis revealed the integration into the genome of 5-20 copies per cell of original plasmid DNA. The plasmid DNA was shown to have tandem organization. PMID- 2924912 TI - Structural basis for the high activation energy of spectrin self-association. AB - The association of spectrin hetero-dimer (alpha beta) to the tetramer (alpha 2 beta 2, which predominates in the cell) is marked by an exceptionally high activation energy, so that the reaction does not proceed measurably in the cold. We have tested the hypothesis that this is due to intra-dimer association between the alpha- and beta-chain ends, which must be broken before tetramers can form. Two mutant univalent spectrins with association defects at the alpha and beta ends, respectively, and incapable therefore of intra-dimer bonding, were found to associate rapidly with one another at 4 degrees C. The bimolecular rate constant is greater than for the association of normal dimers by 6 orders of magnitude. PMID- 2924913 TI - Interaction of the pore forming-peptide antibiotics Pep 5, nisin and subtilin with non-energized liposomes. AB - The cationic peptide antibiotics Pep 5, nisin and subtilin depolarize bacterial and artificial membranes by formation of voltage-dependent multi-state pores. Studies with non-energized liposomes indicated that the peptides do not span the membrane in the absence of a membrane potential. The effects of Pep 5 and nisin on neutral membranes, as studied by membrane fluidity, phase transition points and carboxyfluorescein efflux, were small compared to melittin. Acidic liposomes were affected more strongly, indicative of primarily electrostatic interactions with phospholipid head groups. Subtilin may slightly enter the hydrophobic core as suggested by tryptophan fluorescence quenching and liposome fusion experiments. PMID- 2924914 TI - Cellular distribution of cholesterogenesis-linked, phosphoisoprenylated proteins in proliferating cells. AB - A set of isoprenylated proteins has been detected in rapidly proliferating, suspension-grown murine lymphoma cells. Our evidence indicates that all of these isoprenylated proteins are phosphorylated. Subsequent to a 24 h incubation with mevinolin to deplete the intracellular mevalonate (MVA) level, cells were incubated with [3H]MVA and/or 32Pi and both total cell and subcellular fraction proteins were resolved via 1- and 2-D gel electrophoresis, then assessed via subsequent autoradiography. The phospho-isoprenylated proteins comprise a set spanning a molecular mass range of 21-69 kDa and all dispay acidic pI. MVA derivatized proteins of 21-24 kDa, which consist of multiple isoforms, are present in both cytosolic and nuclear fractions. Larger phospho-isoprenylated protein species (44-69 kDa) are specifically localized within the nucleus, where applicable extraction protocols indicate that they are part of or closely affiliated with the nuclear matrix-intermediate filament (NM-IF) components. The localization of the 69 kDa prenylated species within the NM-IF fraction, together with evidence of its phosphorylation, supports recent indications that this protein is the nuclear matrix component lamin B. PMID- 2924915 TI - Evidence for the appearance of a reticulocyte population low in lipoxygenase mRNA during the recovery from a phenylhydrazine-induced anemia in rabbits. AB - It is shown that during recovery from a phenylhydrazine-induced anemia in rabbits a selective decrease in lipoxygenase mRNA takes place with a corresponding shut off of the synthesis of the enzyme. It is suggested that a new population, 'recovery'-reticulocytes, makes its appearance in the peripheral blood. Their cells are more mature than the stress macroreticulocytes. A cell-free system prepared from the recovery-reticulocytes exhibits low endogenous synthesis of non globin polypeptides, even without nuclease treatment, but retains full capacity to be stimulated by exogenous mRNA. PMID- 2924916 TI - DNA polymerase alpha-DNA primase from human placenta. Immunoaffinity purification and preliminary characterization. AB - Highly purified DNA polymerase alpha-DNA primase from normal human tissue (human placenta) has been prepared by immunoaffinity purification on immobilized anti human DNA polymerase alpha monoclonal antibody SJK 287-38. According to data from SDS electrophoresis this preparation consists of subunits of 180, 160, 145, 140 kDa (a cluster of DNA-polymerizing subunits), 73 kDa (function unknown) and 59, 52 kDa (corresponding to primase). Three active enzyme forms of 270, 460 and 575 kDa have been revealed using native electrophoresis followed by detection of DNA polymerase activity. PMID- 2924917 TI - Modelling basic features of specificity in DNA-aureolic acid-derived antibiotic interactions. AB - The nonintercalative groove binding of a simplified model of olivomycin, to sequences d(CGCGCGC)2, d(TATATAT)2, and d(CICICIC)2 is investigated. A significant preference is displayed for the minor groove of the d(CG) sequence. This is due predominantly to the formation of H-bonds between the hydroxyl groups on the aglycone of the drug and the 2-amino group of the central guanine of the oligonucleotide. PMID- 2924918 TI - A phorbol ester and a daphnane ester stimulate a calcium-independent kinase activity from human mononuclear cells. AB - TPA and a non-promoting, pro-inflammatory ester RX were used to stimulate the forms of PKC isolated from human mononuclear cells. Three peaks of kinase activity corresponding to gamma, beta and alpha PKC were stimulated by TPA in the presence and absence of calcium and/or phosphatidylserine (PS) but were not activated by RX. A fourth peak eluted at high phosphate concentration was activated by TPA and RX in the presence of PS and the absence of calcium. Activity in this fraction was labile to freezing and thawing and was inhibited by staurosporine. PMID- 2924919 TI - Prothymosin alpha is a nuclear protein. AB - The cellular location of the so-called 'thymic hormone' prothymosin alpha has been studied by microinjection into the cytoplasm of Xenopus oocytes, followed by separate monitoring of nuclear and cytoplasmic concentrations. It is shown that prothymosin alpha migrates to the nucleus at a rate comparable to that of histone H1. Prothymosin alpha cannot therefore be a hormone in the usual sense of the word. PMID- 2924920 TI - The human 32-kDa stress protein induced by exposure to arsenite and cadmium ions is heme oxygenase. AB - Exposure of HeLa and HL60 cells to sodium arsenite or cadmium chloride led to marked increases in cellular heme oxygenase activity. SDS-polyacrylamide gel electrophoresis of [35S]methionine-labeled cellular proteins indicated that these treatments also resulted in the induction of a 32-kDa protein. Immunoblot analysis further showed that the 32-kDa protein reacted with anti-bovine heme oxygenase antibodies. Treatment of the cells with cobaltic chloride or heat induced neither the 32-kDa protein nor heme oxygenase activity. It is concluded that the 32-kDa stress protein induced by arsenite and cadmium ions in these human cells is heme oxygenase. PMID- 2924921 TI - Mode of binding of E-64-c, a potent thiol protease inhibitor, to papain as determined by X-ray crystal analysis of the complex. AB - The three-dimensional structure of the E-64-c-papain complex has been determined by X-ray crystal analysis at 2.5 A resolution (conventional R = 26.9%). The structure determined indicates that: (i) the C2 atom of the oxirane ring of E-64 c is covalently bound by the S gamma atom of Cys-25 of papain; (ii) this covalent bond formation results in a configurational conversion of the oxirane C2 atom from the S- to the R-form; and (iii) extensive hydrogen bonding and hydrophobic interactions are responsible for the specific interaction of the E-64-c molecule with papain. PMID- 2924922 TI - Electrostimulation-induced increases in fatty acid-binding protein and myoglobin in rat fast-twitch muscle and comparison with tissue levels in heart. AB - Chronic stimulation of rat fast-twitch muscle increased the content of both fatty acid-binding protein (FABP) and myoglobin. The increases in FABP, which reached values close to that of cardiac muscle, exceeded those in myoglobin and those in citrate synthase and 3-hydroxyacyl-CoA dehydrogenase activities. PMID- 2924924 TI - Selective inhibition of photosystem II in spinach by tobacco mosaic virus: an effect of the viral coat protein. AB - Leaves of Spinacia oleracea inoculated with tobacco mosaic virus (TMV) strain PV230 develop mild chlorotic and mosaic symptoms of infection. Thylakoid membranes isolated from these infected leaves showed a reduced Fv/Fm ratio for chlorophyll fluorescence kinetics, at 25 degrees C. The photosystem II (PS II) mediated electron-transport rate was inhibited 50%, whereas PS I activity was unaffected by virus infection. Protein analysis indicated that TMV coat protein was associated with thylakoids, in particular with the PS II fraction. The results demonstrate that TMV-infected S. oleracea shows inhibition of photosynthetic electron transport through PS II. We propose that the inhibition of photosynthetic activity results from the association of viral coat protein with the PS II complex. PMID- 2924923 TI - Isolation and reconstitution of the high-affinity choline carrier. AB - Monoclonal antibodies, which block the high-affinity uptake of choline in synaptosomal ghosts, have been used to purify a membrane polypeptide (80 kDa) from insect synaptosomal membranes. This isolated protein was found to catalyse the sodium-dependent, hemicholinium-sensitive accumulation of choline after reconstitution into liposomes, thus, apparently represents the high-affinity choline transporter. PMID- 2924925 TI - Effect of acidosis on Ca2+ sensitivity of skinned cardiac muscle with troponin C exchange. Implications for myocardial ischemia. AB - By using a novel approach for the study of the effects of pH variation in skinned myocardium, the present experiments were aimed to provide new insights into the mechanism of ischemia. Ca2+ sensitivity is decreased by acid pH, but the effect is more than double in cardiac myofilaments than that in fast-twitch skeletal muscle fibers. With the technique of troponin C exchange in myocytes, we find here that the effect of pH is the same with cardiac or skeletal troponin C. These results rule out a direct H+-Ca2+ competition on the Ca2+-binding sites of troponin C as a significant mechanism of ischemia. The findings provide conclusive evidence in favor of the idea that acidosis modulates the protein protein interactions in the regulatory complex in cardiac muscle. PMID- 2924926 TI - Amino acid sequence of locust neuroparsins. AB - Neuroparsins A and B were isolated from the nervous part of the corpus cardiaca of Locusta migratoria via a two-step purification procedure. Both consist of two polypeptide chains linked by disulfide bridges. The N-terminal sequence of both native neuroparsins was determined: the N-terminal end of neuroparsin B was unique while that of neuroparsin A showed three different sequences. These sequences were that of neuroparsin B and two others having five and two extra N terminal residues. Neuroparsin B was found as a homodimer and the complete sequence of the monomer, determined from peptide fragments generated by treatment with cyanogen bromide and endoprotease Glu-C, comprises 78 residues. PMID- 2924927 TI - Assisted reproduction: registration vis-a-vis regulation. PMID- 2924928 TI - The incidence of luteal phase defect in normal, fertile women, determined by serial endometrial biopsies. AB - Five regularly menstruating women of proven fertility, with normal prolactin and thyroid function studies, underwent a total of 39 endometrial biopsies (EMBs). The slides were dated in blinded fashion, and the cycle date determined by considering the date of the next menstrual period as day 28 and counting backward. Using a 2-day or greater lag in endometrial maturity to define a luteal phase defect (LPD), the incidence of single and sequential out-of-phase EMBs was 51.4% and 26.7%, respectively. Using a 3-day or greater lag to define a LPD, the incidence of single and sequential out-of-phase EMBs was 31.4% and 6.6%, respectively. These incidences in normal, fertile women are as high as the rates quoted for infertile populations, and call into question the standard criteria for defining this condition and evaluating therapies to correct it. PMID- 2924929 TI - Twenty-four-hour progesterone and luteinizing hormone profiles in the midluteal phase of the infertile patient: correlation with other indicators of luteal phase insufficiency. AB - The authors have further analyzed women diagnosed as having luteal phase insufficiency in hope of determining the value of specific screening tests as well as determining the degree of heterogeneity of pathophysiologic mechanisms involved in the disorder. Twelve women with the disorder were identified, 6 with two consecutive midluteal serum progesterone (P) levels less than 10 ng/ml (group 1) and 6 with two consecutive late luteal phase endometrial biopsies out of phase (group 2); 4 infertile women with normal serum P and late luteal biopsies also were studied (group 3). All underwent serum sampling for P and luteinizing hormone (LH) at 20-minute intervals for 24 hours, beginning at 9:00 A.M. of day 7 post-LH surge. No significant differences were noted among the three groups for LH area under the curve, pulse frequency, or pulse amplitude. Furthermore, no differences were ascertained for P area under the curve. However, individuals were identified who had one or more hormonal abnormalities but no abnormal biopsy, as well as patients with normal hormonal profiles but having abnormal endometrial development. Receiver Operating Characteristic curves demonstrated that pooled morning serum P levels provided optimal predictive ability of biopsy results. The authors conclude that luteal phase insufficiency is a heterogeneous disorder, and that neither endometrial biopsy nor serum hormonal analysis obviates the need for the other. PMID- 2924930 TI - Decreasing serum levels of sex hormone-binding globulin around the menopause and temporary relation to changing levels of ovarian steroids, as demonstrated in a longitudinal study. AB - Blood samples collected longitudinally in 17 women over a period of 3 years, starting 11/2 years before the menopause, were assessed for sex hormone-binding globulin (SHBG), 17 beta-estradiol (E2), progesterone, and total testosterone. A slight (7.2%) decrease in mean SHBG from 4.25 +/- 1.67 (standard deviation) mg/l to 3.95 +/- 1.61 mg/l was observed within the 6-month period encompassing the menopause. More specifically, the decrease appeared to commence at the menopause and to become clearly significant (P = 0.01) some 2 to 6 months later. During the subsequent year, a further decrease to 3.64 +/- 1.42 mg/l was observed, amounting to a total decrease in mean SHBG by 14.4% (P less than 0.001). Of the hormones, only E2 exhibited a marked decrease (P less than 0.01) within this same 6-month period. The changes in SHBG during the 6-month transition period from premenopause to postmenopause correlated significantly (P = 0.013) only with those of E2. It is concluded that decreasing E2 levels appear to play a significant role in the downward modulation of SHBG levels commencing at the menopause. PMID- 2924931 TI - Outcome in 242 in vitro fertilization-embryo replacement or gamete intrafallopian transfer-induced pregnancies. AB - Two centers combined data on 152 in vitro fertilization embryo replacement and 90 gamete intrafallopian transfer generated pregnancies. The outcomes of the pregnancies with respect to abortion, ectopic gestation, and multiple gestation were evaluated independently by method and by center. Only with multiple gestation by center was a difference seen. Variables examined included estradiol levels, luteal phase support, maternal age, and prior reproductive history, and the number of eggs or embryos replaced. PMID- 2924932 TI - A program for matched, anonymous oocyte donation. AB - The authors' program for matched, anonymous oocyte donation has resulted in two successful pregnancies among the first eight oocyte recipients. All oocyte recipients to date have had ovarian failure or absence with premature ovarian failure the most common cause. All recipients were cycled on a program of incremental oral micronized estradiol and intramuscular progesterone-in-oil. Thirteen candidates for oocyte donation were screened to obtain 8 donors. One donor candidate was excluded because of her medical history. The psychological screening of 2 of the other donor candidates (who subsequently did not complete the donation cycle) revealed a primary motive of financial gain. In general, the psychological profiles of donor candidates revealed a high incidence of troubled families and either reproductive loss or loss of a parent. Ovarian stimulation of the donors followed our standard in vitro fertilization protocol. The recipients' exogenous steroid replacement continued until days 97 and 101, respectively, of the two gestations. Both pregnancies resulted in the delivery of normal singleton males--the first at 40 weeks, the second at 35 weeks. PMID- 2924933 TI - Is fresh or frozen semen to be used in in vitro fertilization with donor sperm? AB - Sixty-six partners of either severely oligoasthenospermic or azoospermic men were treated by in vitro fertilization with donor sperm (IVF-D), usually (86%) after failure of artificial insemination with donor sperm. One hundred twenty-nine IVF trials were performed with either fresh (59%) or frozen-thawed (41%) donor sperm. Characteristics of sperm preparations were significantly lower in the frozen thawed group (P less than 0.001). In the latter group, fertilization rates had slightly decreased (but without statistical significance); embryonic vitality scores and cryopreservable spare embryos had significantly decreased (P less than 0.05). However, cumulative ongoing pregnancy rates were strictly equivalent in both groups (40% after three trials). Frozen-thawed sperm thus can be substituted for fresh donor sperm without entailing impairment of the outcome of IVF, and this method must be preferred for its greater safety regarding transmission of human immunodeficiency virus. PMID- 2924934 TI - Hemizona assay: assessment of sperm dysfunction and prediction of in vitro fertilization outcome. AB - The hemizona assay (HZA) was used in a prospective, blinded study to assess the relationship between tight sperm binding in the HZA and sperm fertilizing ability in in vitro fertilization (IVF). In each controlled assay, the authors compared sperm binding of proven fertile men with that of patients undergoing IVF. Human oocytes stored in a salt solution were used in the study, and binding results were correlated with the fertilization rate of preovulatory oocytes during IVF. Patients with poor fertilization rates in IVF had significantly lower binding than those cases with successful fertilization (7.3 +/- 1.4 versus 62.1 +/- 10.9, respectively; mean +/- standard error, P less than 0.02). Based on current standards, the HZA was able to predict fertilization accurately in 26 of 28 cases (sensitivity of 83%, specificity of 95%, positive predictive value of 83%). The authors conclude that the HZA is a valuable tool for evaluating dysfunctional sperm-zona pellucida binding, with good predictive value for fertilization in vitro. PMID- 2924936 TI - Intrauterine insemination is not useful in oligoasthenospermia. AB - A prospective randomized study was conducted in 47 couples with infertility due to subnormal semen to compare luteinizing hormone (LH)-timed intrauterine insemination with LH-timed natural intercourse. No pregnancy occurred in 114 cycles of intrauterine insemination with washed sperm. Only one patient conceived during 1 of the 124 natural intercourse cycles. The only complication that occurred after intrauterine insemination was mild abdominal cramp in 3 cycles. The authors conclude that intrauterine insemination is not useful in the management of subfertility due to oligoasthenospermia. PMID- 2924935 TI - Cell-free human amniotic fluid as culture medium for mouse and human embryos. AB - Differences between murine and human preimplantation embryonic growth in cell free human amniotic fluid and medium F-10 supplemented with human fetal cord serum were assessed. Two-cell mouse embryos cultured in human amniotic fluid developed more consistently to the expanded blastocyst stage than those cultured in F-10. No significant difference in human preimplantation embryo cleavage was observed between the two culture conditions. However, amniotic fluid was significantly worse than F-10 + human serum in its ability to maintain embryos that could establish pregnancy after transfer. PMID- 2924937 TI - Human sperm selection by glass wool filtration and two-layer, discontinuous Percoll gradient centrifugation. AB - Glass wool filtration and two-layer, discontinuous Percoll (Pharmacia, Uppsala, Sweden) density gradient centrifugation resulted in an average recovery of 50% to 70% of the progressively motile and about 50% of the hypoosmotic swelling (HOS) positive spermatozoa. Glass wool filtration tended to be more successful than Percoll centrifugation when the ejaculates were asthenozoospermic or produced a suspect/abnormal HOS test. After selection, the acrosin activity increased approximately two- to threefold, but no significant improvement in the percentage of normal sperm forms occurred. Experiments with mixtures of untreated and frozen thawed ejaculates confirmed that glass wool filtration is more effective in removing nonmotile and HOS-negative spermatozoa than the two-layer Percoll centrifugation technique when the percentage of these types of spermatozoa in the ejaculate is high. The simplicity of these techniques and the good recovery of apparently viable spermatozoa makes these methods more desirable than other, more complicated techniques or procedures that yield a lower recovery of motile spermatozoa. PMID- 2924938 TI - A zona opening procedure for improving in vitro fertilization at low sperm concentrations: a mouse model. AB - Micromanipulation was used for creating a small opening in the zona pellucida without damaging the ooplasm of oocytes. This was applied in mouse in vitro fertilization as a model for inseminating oocytes with low sperm concentrations. It was found that the opening in the zona did not influence the fertilization rate at 10(5) sperm/ml, but when the sperm concentration was decreased to 10(4)/ml, the oocytes containing the break had a significantly higher fertilization rate and blastocyst development, compared with their intact controls. The zona cracking procedure did not increase parthenogenetic activation nor polyspermic fertilization, although it did promote early hatching of some blastocysts. The birthrate of normal offspring was not affected by exposing oocytes to the zona opening process. PMID- 2924939 TI - Autoantibodies to laminin and other basement membrane proteins in sera from monkeys with histories of reproductive failure identified by cultures of whole rat embryos. AB - Head-fold-stage rat embryos cultured on sera taken from monkeys with histories of reproductive failure had an abnormality frequency of 97% compared with only 7% on sera taken from monkeys with excellent reproductive histories. For a group of these poor reproducers, the toxicity of their sera was associated with the immunoglobulin G (IgG) fraction. These IgG fractions bound to Reichert's membrane and other basement membranes of the embryo. For one monkey, the IgG specifically reacted with a 41 kDa polypeptide of Reichert's membrane, while for two others binding was to laminin, type IV collagen, and several other minor polypeptides of Reichert's membrane. For serum from one monkey, the toxicity to cultured rat embryos was eliminated by absorption with laminin but not type IV collagen. PMID- 2924940 TI - Improving penetrating capacity of spermatozoa with poor motility by addition of caffeine at coincubation with zona-free hamster ova. PMID- 2924941 TI - Effect of nicotine on in vitro human sperm penetrability through cervical mucus and motility parameters. AB - Nicotine at concentrations found in the cervical mucus of female smokers appeared to enhance in vitro human sperm penetrability through ovulatory bovine cervical mucus. Sperm motility parameters were not affected by the addition of nicotine to semen samples incubated with BWW medium. Overall, these results suggest that a direct inhibitory effect of nicotine on sperm penetrability through cervical mucus is not responsible for the apparent increase in cervical factor infertility present in smoking women. PMID- 2924942 TI - Combined intrauterine and cervical pregnancy from in vitro fertilization and embryo transfer. PMID- 2924943 TI - Delivery of twins to a woman with surgically induced menopause after oocyte donation by the sister and cryopreservation of the conceptuses. PMID- 2924944 TI - Conception through a cervicovaginal fistula. PMID- 2924945 TI - Local reaction to progesterone. PMID- 2924946 TI - Progesterone for diagnosis of ectopic. PMID- 2924947 TI - Does minimal endometriosis cause infertility? PMID- 2924948 TI - [Gouty tophus of the temporomandibular joint]. AB - A rare case of gouty tophus localized to the temporomandibular joint is reported on by which alimentary troubles were caused. Establishment of clinical diagnosis was rendered more difficult by lack of gauty anamnesis. PMID- 2924950 TI - [Use of the Fistulamat instrument in the preparation of surgical fistulae]. AB - Describes the Fistulamat instrument designet and used by Sargenti. Endotontological cases are listed where the instrument may be used successfully and where its employment is counter indicated, respectively. PMID- 2924949 TI - [Deciduous incisors with a serrated edge]. AB - In contrast to the opinion accepted in the literature also the edge of the milk incisors can be triple indented. Among 619 milk incisors, examined on infants, 68 were indented, approximately 11%. Within the group of milk incisors most frequently the lower one is indented edge, in about 16%. PMID- 2924951 TI - [Ambulatory anesthesia in pediatric dentistry]. AB - Complex dental care has been performed on 180 mentally retarded children difficult to manage in general narcosis. Ketalar (Parke-Davis) employable also im. and iv. and its Hungarian counterpart the Calypsol (Kobanyai Gyogyszerarugyar), respectively, was employed for narcotics. PMID- 2924953 TI - Transesophageal atrial pacing with stress echocardiography. PMID- 2924954 TI - Chest tubes at the cemetery. PMID- 2924952 TI - [Congenital hypophosphatasia as a possible cause of early loss of deciduous teeth]. AB - The suspicion of congenital hypophosphatasia is frequently raised byte premature falling out of milk teeth. The diagnosis is corrobarated by the characteristic bone deformities, by the high selection of phosphoetanomalin and by the diminished alkaline phosphataze enzyme activity of the serum. The case of a four years old boy patient is reported on. PMID- 2924955 TI - Acquired immunodeficiency syndrome and human immunodeficiency virus testing: privacy and confidentiality concerns. PMID- 2924957 TI - Understanding and managing myasthenia gravis. PMID- 2924956 TI - Potential for infection: a nursing diagnosis for the patient with an indwelling catheter. PMID- 2924958 TI - Patient self-efficacy: a framework for designing patient education. PMID- 2924959 TI - [The role of the heart in rewarming the body of hibernating animals upon arousal]. AB - The heart of ground squirrels is covered by a large amount of brown adipose tissue during the whole period of hibernation. During arousal and rewarming of heterothermal rodents, the highest temperature is detected in the brown adipose tissue and in the heart. During hibernation the heart rate is 10-12/min. On arousal, beginning from the early stage when the heart temperature is still low, a significant increase in the heart rate occurs followed by acceleration of the body rewarming of heterothermal animals. PMID- 2924960 TI - [The effect of triiodothyronine and catecholamines on the stability of trace effects of cold adaptation in rats]. AB - The role of three-iodine-thyronine, noradrenaline (NA), adrenaline (A), reserpine and propranolol in extinguishing of trace-effects of the long-term cold adaptation was studied in rats. A possibility to control the process of the temperature disadaptation through administration of different hormonal drugs, was shown. Three-iodine-thyronine and NA proved to be the most effective in this respect. Weakening of sympathetic-adrenal effects by means of combined reserpine and propranolol during the disadaptation accelerated the process of extinguishing of practically all the trace-effects of the long-term cold adaptation. PMID- 2924961 TI - [The functional value of the dynamic activity of cold receptors of the skin]. AB - During abrupt cooling the dynamic activity of skin cold receptors is observed whereas it is practically absent during slow cooling. The influence of these two types of cooling on metabolic and skin blood vessels responses was studied in anesthetized rats. Acceleration of the cooling decreased the skin temperature threshold for metabolic response while the threshold for skin blood vessels constriction increased. PMID- 2924962 TI - [Hormonal homeostasis and intraocular pressure in chronic emotional stress caused by influences acting on the amygdala]. AB - Changes in intraocular pressure, eye hydrodynamics and the amount of hypophyseal, thyroid, adrenal and pancreatic hormones were studied during continuous stimulation of amygdaloid complex or after administration of angiotensin II into the structure in rabbits. The effects involved changes in hormonal homeostasis and elevation of intraocular pressure due to a hypersecretion of intraocular fluid. The administration of angiotensin II during the amygdala stimulation enhanced the changes. PMID- 2924963 TI - [Interhormonal relations in the dynamics of immune response during thyroidectomy]. AB - Wistar rats were immunized with the sheep erythrocytes (SE) within 18 or 60 days after thyroidectomy. The latter led to a sharp drop in concentration of T3, T4 and to 2-3-fold increase in the TTH level. The SE administration failed to induce an increase in the T3, T4 level in operated animals whereas the TTH concentration increased. During the inductive period of immunogenesis a reduction occurred in the antigen-induced glycocorticoid response and the testosterone level in the early period replaced by their increase in later stages after the operation. The intensity of antibody production decreased in the early period and increased later. The data obtained suggest a participation of these changes of the endocrine functions in the mechanisms of thyroidectomy-induced disorders of the immune response. PMID- 2924965 TI - [Indicators of systemic and regional hemodynamics in alert rats or rats anesthetized with nembutal or urethane]. PMID- 2924964 TI - [Corticosteroid response and indolamine content of the mouse brain under the action of a pheromone, disrupting spermatogenesis]. AB - The volatile components of adult male urine from laboratory mice of CBA/LacSto strain inhibited spermatogenesis in CBAB6F1 30-day old mice. There were no significant responses in hypothalamic and olfactory bulb indolamine systems, neither in the blood corticosterone level of the mice during experimental treatment. A prolactin mechanism of the pheromone inhibition of testicular function is suggested. PMID- 2924966 TI - [Changes in the dopamine level in dialysate from the rat striatum after administration of phenamine into the nucleus accumbens]. PMID- 2924967 TI - [An automatic adapter for the Simonov chamber]. PMID- 2924968 TI - [Electrochemical phenomena in autoregulatory reactions of the blood vessels]. AB - Some physiological mechanisms being in the basis of autoregulatory reactions of blood vessels have been studied. It has been found that the rise in the difference of the potentials of electrochemical origin between inner and exterior vessel surfaces during blood movement facilitates to increase the vessel myogenic reaction at the intravascular pressure rise, to intensify spontaneous bioelectrical activity of smooth muscle cells and hydration of a vascular wall. These phenomena are reproduced by the application to a vessel a constant potential commensurable with one rising during blood movement. PMID- 2924969 TI - [The effect of the opioid peptide dalargin on the regeneration of the rat sciatic nerve]. AB - The effect of synthetic analog of leucine enkephalin hexapeptide dalargin on regeneration of peripheral nerves involved an activation of the sensory and motor fibers regeneration after transection and microsurgical restoration of the rat sciatic nerve. Endogenous opioid peptides seem to take part in the regulation of structural homeostasis of the nervous system. PMID- 2924970 TI - [Morpho-functional characteristics of erythrocyte redistribution in various vascular regions]. AB - A qualitative differentiation of the blood flow was found to occur at the level of aortic arch. Erythrocytes from the carotid artery differ from those of the femoral artery by their morphofunctional parameters (surface area, lipoprotein contents, sulfhydryl groups, hemoglobin). The data obtained suggest that the erythrocytes entering the brain are younger and functionally more active. They are supposed to take part in the mechanisms supporting a stable functional condition of the brain. PMID- 2924972 TI - [The mechanism of lymphodynamics in orthostatic dogs during postnatal ontogenesis]. AB - In acute experiments on anesthetized puppies of one-day to three months of age the influence of orthostatic posture (30 degrees) on the lymph flow and arterial pressure was studied. One-day old puppies developed an increase in arterial pressure whereas older animals developed opposite changes. The lymph flow was drastically diminished in orthostatic posture and increased when the animals returned to the initial position. The time course and the intensity of the alterations in the lymph flow depended on the age. In growing animals subjected to passive orthostatic tests the characteristics of alterations in the lymph flow were related to morphological and functional development of the lymphatic channel in postnatal ontogenesis. PMID- 2924971 TI - [Participation of the cholinergic system in the development of hemodynamic effects of GABA, administered intrabulbarly]. AB - Acute experiments in cats revealed effects of GABA injections (2.10(-5)-5.10(-5) M/l) into the neuronal structures of the dorso-medial medulla after M cholinoreceptors had been blocked. Hypotensive action of GABA injected into the n. ambiguous and ventral reticular nucleus was shown to be actualized through participation of bulbar M-cholinoreceptors. Effects of GABA injected into n. tractus solitarius occurred with no consistent participation of the central M cholinoreceptors. PMID- 2924973 TI - [The effect of neurohypophyseal peptides on the formation of conditioned active avoidance behavior]. AB - An injection of vasopressin and its analog into ventral hippocampus facilitated the formation of avoidance response and inhibited the behavioural habit in the process of extinction. Opposite effects occurred after administration of oxytocin and its fragment. The changes observed in the avoidance paradigms motivated by fear seem to be related to effects of the peptides under study on the processes of learning and memory. PMID- 2924975 TI - [Interstitial volume receptors of the liver]. AB - The study of the impulse activity of single afferent hepatic fibers in depth has found out that there are volume-sensitive units reacting upon the short-time infusion of the different test solutions into the portal vein. But they are displaying complex dependence of the response's characteristics not only on the magnitude increasing in intraportal volume but also on "quality" of the infused substance and total quantity of the injected fluid. There are units both responding for infusion period and after it with the latencies from 10 s to 2-3 min. The second phase of these units responses was more pronounced than the first one. The response patterns of the studied units are convincing data on an interstitial localization of the one type volumereceptors and a vasal interstitial localization of the others. The results suggest that the significant role in the control of the water-salt homeostasis is played by these receptors. PMID- 2924974 TI - [Evacuatory activity and motor periodicity of the stomach after transposition of the pancreatic duct into the jejunum]. AB - The transposition of the pancreatic duct into the jejunum accelerated the evacuation of acid solution from the stomach while decelerating that of bicarbonate solution. The motor periodicity of the stomach obviously changed, at that: the duration of working and resting phases, the rate and the strength of the stomach contractions. The data obtained suggest regulatory effects of the pancreatic juice from the duodenum upon the stomach motor-evacuatory activity. PMID- 2924976 TI - [Central mechanisms of thermoregulation and phase transitions of brain lipids pertaining to them]. AB - The experiments in rats and rabbits revealed a correlation among the body temperature, the peripheral temperature threshold, central (thermosensitive neurons) thermoregulatory responses, and the temperature of phasic transition of brain lipids three latter parameters rising during experimental fever. The composition of phospholipids changed in hypothalamic tissues, i.e. the level of saturated fatty acids radicals increased. PMID- 2924977 TI - Effect of selected antioxidants on the stability of dehydrated mashed potatoes. AB - The antioxidants TBHQ, alpha-tocopherol, Prolong P (rosemary, thyme, marjoram mixture) or ascorbyl palmitate were not found able to replace the antioxidant BHA in potato flakes production if stored for up to 24 months. Ascorbyl palmitate gave good antioxidative protection up to 16 months of storage, and also protected against carotenoid degradation better than the other antioxidants. The ascorbyl palmitate lost its antioxidative effect after longer storage. PMID- 2924978 TI - Chromium and nickel in roadside grapes. AB - Chromium and nickel concentration in roadside unwashed wine grapes and leaves is considered as a function of the distance from the suspected source, an isolated straight road. The analyses were performed with electrothermal atomization in a graphite furnace. The decrease in the concentration of the element can be described by means of a three-parameter exponential function c = A + (B - A)exp( Cd), which allows the determination of the asymptotic level far from the emitting source (C infinity) and the pollution level (C0) at the edge of the road (d = 0). Least-squares nonlinear regression gives the estimation of the parameters A, B, and C. The results indicate that an effect is detectable up to a distance of about 50 m. PMID- 2924979 TI - Monitoring Ontario-grown apples for pest control chemicals used in their production, 1978-86. AB - Between 1978 and 1986, 305 samples of apples were monitored for the residues of a wide range of pesticides used in their production. Three (1%) contained residues above the maximum residue limits (MRL) permitted under the Canadian Food and Drug Act and regulations; two involved phosalone at 5.9 and 6.2 mg/kg respectively and one involved diphenylamine at 6.7 mg/kg when the MRL was 5.0 mg/kg for both compounds. Low residues of dicofol, endosulfan, phosalone, phosmet, captan, daminozide and diphenylamine were frequently found; however they were well below the MRLs. These residue levels were correlated with survey data on the areas of the apple crop treated with specific pesticides. Residues of carbaryl, diazinon, ethion, azinophosmethyl, parathion, and dithiocarbamate fungicides were found occasionally; all were well below the MRLs and correlated with the pattern of use. No residues of PCB were found to a limit of detection of 0.01 mg/kg. PMID- 2924980 TI - In vivo effects of terbinafine and ketoconazole on testosterone plasma levels in healthy males. AB - Ten healthy male volunteers received daily 200 mg of ketoconazole or 500 mg of terbinafine (SF 86-327) for a period of 8 days according to a crossover double blind design. Between the periods of treatment there was an interval of 3 weeks. Before and during the treatments, on 3 days in all, blood levels of testosterone were determined in the morning at 08.00 and 12.00 h. On the following day in each case, after taking a basal blood sample, 5,000 IU of hCG were injected intravenously and 2 h later a further blood sample for plasma testosterone determination was taken (short-term hCG stimulation test). Prior to treatment, the mean plasma testosterone levels at 12.00 h were slightly below the level at 08.00 h (6.5 +/- 3.5 against 7.2 +/- 3.1 ng/ml). The difference increased and was statistically significant with ketoconazole treatment (4.2 +/- 3.2 against 7.7 +/ 3.0 ng/ml), but did not alter during administration of terbinafine (7.8 +/- 4.4 against 6.8 +/- 3.0 ng/ml). The administration of testosterone levels by hCG stimulated 25.6% prior to treatment. The stimulation was suppressed to zero by ketoconazole but clearly intensified (41.7%) by terbinafine treatment. The results demonstrate once more the well-known effect of ketoconazole on testosterone production and confirm that terbinafine obviously does not have this effect. PMID- 2924981 TI - Tinea of the glans penis. AB - A 56-year-old Japanese man with tinea of the glans penis is described. He did not carry any other tinea lesions except that of the glans penis. Mycological examinations revealed that the causative organism was Trichophyton mentagrophytes. PMID- 2924982 TI - Nd:YAG laser therapy of an oral verrucous leukoplakia. AB - A 75-year-old female patient afflicted with an extensive verrucous oral leukoplakia is reported. With treatment by the Nd:YAG laser under local anesthesia on an outpatient basis, the disease could be kept under control for 4 years. PMID- 2924983 TI - Werner's syndrome and astrocytoma. AB - Werner's syndrome, a relatively rare and autosomal recessive disorder, is well known to be characterized by a high frequency of malignant neoplasms. Werner's syndrome has not infrequently been associated with meningiomas. We report a case of Werner's syndrome and temporal astrocytoma in a 49-year-old male. As far as we are aware, this is the first report of the association of Werner's syndrome and astrocytoma. PMID- 2924984 TI - Epidermal proliferation and accumulation of polymorphonuclear leukocytes in the psoriatic lesion. AB - Biopsies were removed from the margin of plaques in 11 untreated psoriatic patients, and 8-microns sections prepared using the cryostat. Alternate sections were stained with H and E to assess the accumulation of polymorphonuclear leukocytes. The remaining sections were stained with the monoclonal antibody Ki67 in order to determine the number of cycling epidermal cells. In areas where polymorphonuclear leukocytes occurred in the stratum Malpighi the number of cycling epidermal cells was relatively low. In contrast, a positive correlation was shown between the density of microabscesses of Munro and the number of cycling epidermal cells. The clinically uninvolved skin of psoriatic patients shows a moderate enhancement of epidermal growth in the absence of any infiltrate. In the lesional skin the recruitment of cycling epidermal cells does not coincide with the invasion of polymorphonuclear leukocytes into the epidermis, but rather follows the penetration of these cells. PMID- 2924985 TI - Significance of squamous cell carcinoma-related antigen in psoriasis and generalized eczema. Preliminary report. AB - The serum levels of squamous cell carcinoma-related antigen (SCC-RAG) were assayed in 15 cases of benign dermatoses. The SCC-RAG titers (2.0 ng/ml as the cutoff value) were elevated in all cases of wide-spreading psoriasis (7 cases, 2.4-96.1 ng/ml) and all cases of generalized eczema (3 cases, 11.2-33.6 ng/ml). The serum SCC-RAG levels correlated with clinical course of these dermatoses. Therefore, the increase in this cancer-related antigen is not specific for SCC but may also occur in a wide range of dermatoses. PMID- 2924986 TI - Increased mast cell numbers in the sclerotic skin of porphyria cutanea tarda. AB - We quantitated numbers of mast cells in the sclerotic skin noted on the dorsa of the hands of 10 patients with porphyria cutanea tarda (PCT), and compared them with those of diffuse scleroderma and healthy controls. Mast cell counts in sclerodermoid skin of PCT patients were significantly greater than those in involved skin of 9 patients with diffuse scleroderma in its late stage and also greater than those in normal skin of 8 controls. When mast cell density was analyzed according to the depth of the dermis, an 84% increase was noted in the uppermost layer (0-0.2 mm in depth) and a 150% increase in the second uppermost layer (0.2-0.4 mm in depth) in the patients with PCT when compared with those in the corresponding sites of the controls. These results suggest a possible role of mast cells in the pathogenesis of sclerodermoid skin of PCT. PMID- 2924987 TI - Investigations on the development and regression of corticosteroid-induced thinning of the skin in various parts of the human body during and after topical application of amcinonide. AB - In 15 subjects 6 different parts of the body were treated with the potent topical corticosteroid (CS) amcinonide once a day for 21 days. The skin thickness of the treated areas was measured sonographically at intervals of 2 days. After completion of the CS application the regression of the CS-induced reduction in skin thickness was measured for a further 14 days. A clear thinning of the skin could be measured after only 4 days and continued up to the 21st day of treatment. This thinning regressed completely in all areas after 10-12 days. The thinning and regression curves were very similar for all body areas. Differences in intensity of thinning were evident. No tachyphylaxis was detected. PMID- 2924988 TI - Severe intra-uterine growth retardation: obstetrical management and follow up studies in children born between 1970 and 1985. AB - Peri- and postnatal data of 263 children with severe intra-uterine growth retardation (IUGR) born between 1970-75 (n = 145) and between 1976-85 (n = 118) are presented. The incidence of premature delivery in IUGR patients rose from 15% (1970-75) to 34% (1976-85). The rate of perinatal asphyxia in premature children with IUGR decreased from 64% during 1970-75 to 45% during 1976-85. Perinatal mortality in preterm SFD babies was higher in 1976-85 (20%) than in 1970-75 (14%), due to an 8-fold higher incidence of very low birth weight (less than or equal to 1000 g) SFD babies. Without this high-risk group perinatal mortality ranged between 2 and 3% in both groups. The incidence of deliveries by Cesarean section increased from 19 to 45% while vaginal deliveries decreased from 73 to 52% during 1976-85 compared with the 1970-75 age group. Follow up studies were carried out in 63 patients (1970-75) and in 41 patients (1976-85). Deficits of body height and weight persisted in one third of the patients, being severe in 10 20%. Infantile developmental milestones were retarded in 22-32%. Neurologic sequelae mostly of a mild degree were seen in 29% (1970-75) and 37% (1976-85). Psychologic testing showed abnormalities in 38% of the older age group, using the Gottinger Formreproduktionstest and in 21% of the younger age group, where the Denver Developmental Screening Test was performed. EEG investigations demonstrated unspecific abnormalities of a mild to moderate degree in one third of the patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2924989 TI - Insulin-like growth factor (IGF-I) and its low molecular weight binding protein in human milk. AB - Insulin-like growth factors (IGF-I and IGF-II) are mitogenic polypeptides bound in serum to specific binding proteins. This study reports the occurrence and concentrations of IGF-I and its low molecular weight IGF binding protein (IGF BP) in human milk and serum after delivery in 41 healthy women. The levels of IGF-I in milk declined between 4 and 92 hours postpartum from 49 +/- 17 micrograms/l to 29 +/- 27 micrograms/l (p less than 0.01). The level of IGF BP also declined from 165 +/- 80 micrograms/l to 97 +/- 70 micrograms/l (p less than 0.01), whereas the serum concentration of this protein remained unchanged. A positive correlation was observed between the individual levels of IGF-I and its binding protein in milk (r = 0.49, p less than 0.01), but no correlation was found between the individual levels of 34 kDa IGF BP in milk and serum. The relative abundance of IGF BP in the first milk compared to IGF-I is intriguing and its biologic significance remains to be clarified. PMID- 2924990 TI - Epidural block or parenteral pethidine as analgesic in labour; a randomized study concerning progress in labour and instrumental deliveries. AB - A prospective randomized study was performed to evaluate the influence of epidural analgesia compared to parenteral pethidine in parturients with pain in the first stage of labour on the progress of labour and the frequency of instrumental deliveries. There was no significant difference in the two groups in the duration of either the first or second stage of labour. The overall instrumental delivery rate was 25%, with no difference between the groups. The analgesic efficacy of the epidural blockade was significantly better than that of parenteral pethidine. We conclude that epidural bupivacaine with our technique and obstetric practice did neither prolong labour nor increase the frequency of instrumental delivery. PMID- 2924991 TI - Second trimester chorioamniotic separation and amniocentesis. AB - On ultrasound, we saw 12 women with a pathological amount of chorioamniotic separation (CAS) in the second trimester. Six were examined before amniocentesis and five were scanned for unsafe dates. In one patient CAS was diagnosed the day after amniocentesis. All women were asymptomatic. Despite CAS, amniocentesis was performed in six patients. The five others served as controls. The overall pregnancy outcome was favorable. Nine delivered living term babys. One patient, with brownish discolored amniotic fluid on amniocentesis, presented with fetus mortuus in week 28. One patient delivered preterm in week 32. In the control group one woman aborted shortly after diagnosis. In no case did the CAS increase after amniocentesis. In conclusion it appears safe to perform amniocentesis in women with asymptomatic CAS, although we recommend not to pass the needle through the separated membranes. PMID- 2924993 TI - Collagen type III in ovarian tumors. Histological, immunohistochemical and ultrastructural findings. AB - The occurrence and location of interstitial collagen amino-terminal propeptide type III procollagen (PIIIP) and fibronectin was studied in 123 ovarian tumors of different types and related to the histological type and clinical behavior of the neoplasm. The purpose was to further our understanding of the development and classification of these tumors and to determine characteristics of diagnostic and prognostic significance. PIIIP-positive fibers were common in the stroma of all types of neoplasms, condensation of fibres occurred at the epithelial-stromal interface of surface epithelial tumors, and disintegration and discontinuation of fibers around invasive epithelial islets and in stroma of undifferentiated epithelial carcinomas. The PIIIP-positive stromal meshwork surrounded individual cells in thecomas, while it was virtually absent in diffuse granulosa cell tumors and distinctly developed in malignant stromal neoplasms, being seen mainly around epithelial islets in mixed mesodermal tumors. PMID- 2924992 TI - The role of chlamydial serology in fertile and subfertile men. AB - The incidence of serum antibodies to Chlamydia trachomatis and the possible association of a positive serology on semen parameters in 120 subfertile men were studied. The findings were compared with those of 120 fertile volunteers fathering two or more children. The two groups were divided into those without and those with a history of genito-urinary infection. There was no significant difference (p greater than 0.1) in the prevalence of antibody testing between the subgroups of fertile population. A statistically significant difference in the incidence of antibodies was found between the two subgroups of subfertile population. No significant difference was noted in the semen parameters between Chlamydia-positive and Chlamydia-negative fertile and subfertile patients. PMID- 2924994 TI - Embryonal rhabdomyosarcoma of the vagina associated with pregnancy; a case report. AB - A case of embryonal rhabdomyosarcoma of the vagina associated with pregnancy is described. This patient delivered a healthy baby by elective classical Caesarean section; following this she was treated by radiotherapy and chemotherapy. The patient is well after 3 years of treatment. PMID- 2924995 TI - Expression and hormonal control of a new larval cuticular multigene family at the onset of metamorphosis of the tobacco hornworm. AB - The pattern of cuticular protein synthesis by the epidermis of the tobacco hornworm larva changes during the final day of feeding, leading to an alteration in cuticular structure and a stiffening of the cuticle. We have isolated a small multigene family which codes for at least three of the new cuticular proteins made at this time. The five genes which were isolated from this family map to two different genomic regions. Sequencing shows that one of the genes is 1.9 kb and consists of three exons coding for a 12.2-kDa acidic (pI = 5.26) protein that is predominantly hydrophilic. The deduced amino acid sequence shows regions of similarity to proteins from flexible lepidopteran cuticles and from Drosophila larval and pupal cuticles, but not to proteins found in highly sclerotized cuticles. This gene family is first expressed late on the penultimate day (Day 2) of feeding in the final larval instar and ceases expression 2 days later when metamorphosis begins. In situ hybridization shows that this gene family is expressed in all the epidermal cells of Day 3 larvae except the bristle cells and those at the muscle attachment site. Expression can be induced in Day 1 epidermis by exposure to 50 ng/ml 20-hydroxyecdysone in vitro, but only if juvenile hormone is absent. Its developmental expression, tissue specificity, and hormonal regulation strongly suggest that this multigene family is involved in the structural changes that occur in the larval cuticle just prior to the onset of metamorphosis. PMID- 2924996 TI - Coordinate accumulation of troponin subunits in chicken breast muscle. AB - The accumulation of troponin subunits in developing chicken breast muscle was determined by two-dimensional gel electrophoresis and an image analyzing system. Many troponin T isoforms, including those hidden behind creatine kinase, were detected on the two-dimensional pattern by the addition of 6 M urea in the second dimension. These troponin T isoforms were classified into four types by developmental order, isoelectric point, and molecular weight: leg-muscle type (L), neonatal breast-muscle type (BN), young chicken breast-muscle type (BC), and adult breast-muscle type (BA). The L-, BN-, and BC-type troponin Ts were transiently expressed at specific developmental stages. Quantitative analysis of two-dimensional patterns of troponin subunits including troponin I and troponin C showed moderate coordination in accumulation among the three subunits throughout postnatal development, when the total amount of all isoforms of troponin T was taken into account. PMID- 2924997 TI - Genetic control of sexually dimorphic axon morphology in Drosophila sensory neurons. AB - The mechanism by which orderly axonal projections are formed during development remains an important and largely unsolved problem in neurobiology. It may be possible to examine the control of axon growth in Drosophila and take advantage of genetic tools to better understand the phenomenon. We show here that some gustatory axons in Drosophila are sexually dimorphic and that genes involved in sex determination control the anatomy of these axons. Both males and females possess gustatory receptors on their legs but males possess more of these receptors than females. More significantly, the axons of the male receptors usually cross the midline and they never do so in females, indicating a central zone of bilateral input in the male but not in the female nervous system. In chromosomal females, expressing a tra or Sxl mutation, the gustatory system is transformed toward the male phenotype. Mutant XX adults resemble normal males externally, because they have more gustatory receptors, and internally, because their axons cross the midline. Gynandromorphs show that the sex of the sensory neuron, and apparently not the central nervous system, controls the growth of the axons. We conclude that the anatomical site of control for this dimorphism is the gustatory neurons. PMID- 2924998 TI - Evolutionary modification of cell lineage in the direct-developing sea urchin Heliocidaris erythrogramma. AB - The sea urchin Heliocidaris erythrogramma undergoes direct development, bypassing the usual echinoid pluteus larva. We present an analysis of cell lineage in H. erythrogramma as part of a definition of the mechanistic basis for this evolutionary change in developmental mode. Microinjection of fluoresceinated tracer dye and surface marking with vital dye are used to follow larval fates of 2-cell, 8-cell, and 16-cell blastomeres, and to examine axial specification. The animal-vegetal axis and adult dorsoventral axis are basically unmodified in H. erythrogramma. Animal cell fates are very similar to those of typically developing species; however, vegetal cell fates in H. erythrogramma are substantially altered. Radial differences exist among vegetal blastomere fates in the 8-cell embryo: dorsal vegetal blastomeres contribute proportionately more descendants to ectodermal and fewer to mesodermal fates, while ventral vegetal blastomeres have a complementary bias in fates. In addition, vegetal cell fates are more variable than in typical developers. There are no cells in H. erythrogramma with fates comparable to those of the micromeres and macromeres of typically developing echinoids. Instead, all vegetal cells in the 16-cell embryo can contribute progeny to ectoderm and gut. Alterations have thus arisen in cleavage patterns and timing of cell lineage partitioning during the evolution of direct development in H. erythrogramma. PMID- 2924999 TI - Drinking behavior and motor function in rat pups depleted of brain dopamine during development. AB - The ability of rat pups depleted of brain dopamine (DA) at either 3 or 15 days of age to increase fluid intake in response to intracellular dehydration was studied. Despite near-total depletions of striatal DA, animals depleted at either age ingested normal amounts of fluid even as soon as 3-7 days after incurring the brain damage. The effects of DA receptor blockade on ingestion and motor function were also studied. Haloperidol had markedly different effects as a function of the age at which the depletions were sustained. Weanlings that were depleted of DA at 3 days of age failed to exhibit the drug-induced adipsia, akinesia, and catalepsy seen in controls and animals that were depleted at 15 days of age. These findings suggest that the DA depletions were performed at different periods of brain organization. The resultant neural controls of ingestion and motor function are qualitatively different in the two groups of depleted animals. Rats depleted at 3 days of age utilize nondopaminergic mechanisms, whereas animals lesioned at 15 days of age continue to rely upon residual DA neurons for both behaviors. PMID- 2925000 TI - Prestimulation effects on blink and cardiac reflexes of 15-month human infants. AB - Reduction of reflex startle by brief changes in prestimulation is a robust phenomenon in adults of several species. Although the phenomenon does not require structures above midbrain, it has a long and uneven developmental course. This study of human infants assessed prestimulus effects at 15 months, within a period which has failed, in past work, to show the usual inhibitory modulation. Magnitude and onset latency of the startle blink and concurrent changes in heart rate were measured under four conditions: 2 single-stimulus conditions, 25-msec, 84-dB, 1000-Hz tone or 50-msec, 109-dB white noise; 2 paired-stimulus conditions, noise bursts preceded by tone at lead times of 125 msec or 225 msec. Compared to noise-alone, paired conditions elicited insignificant increases in blink size, significant shortening of blink onset latency, and significant attenuation of heart rate responses. The findings add to growing evidence of a dissociation between modulating effects on blink magnitude and latency and of a dissociation between modulating effects on somatic and autonomic reflexes. PMID- 2925001 TI - The role of homecage environmental stimuli in the facilitation of shock-motivated spatial discrimination learning in rat pups. AB - In three experiments we examined the role of homecage environmental stimuli on learning an aversively motivated spatial discrimination task in 11-day-old rats. Varying the presence and absence of nest shavings in the correct and incorrect arms of a T-maze in Experiment 1 revealed that nest shavings had both nondirective facilitation and approach-eliciting properties. Training the 11-day old rats in the presence or absence of shavings over three daily sessions and comparing their performance on the third day of training with that of a maturation control in Experiment 2 indicated that there is a residual training effect of the approach-eliciting property of nest shavings on shock-escape behavior. In Experiment 3, using nest shavings either as an irrelevant stimulus or as a redundant relevant cue in an aversively motivated T-maze reversal task suggested that 11-day-old rats acquire the discrimination task using non-nest spatial or directional cues as well as those provided by nest shavings. Overall, these results suggest that nest shavings introduced into aversively motivated tasks create a learning environment comparable to that of appetitively motivated instrumental tasks utilizing suckling from an anesthetized dam as a reinforcer. PMID- 2925002 TI - Activity states and motor activity in an infant capuchin monkey (Cebus apella) from birth through eleven weeks. AB - Behavioral states and motor activity of an infant capuchin monkey reared by its mother in a social group were studied for 11 weeks after birth. Manipulative activity was infrequent through the first four weeks after birth; what little occurred was mediated by other animals interacting with the infant. The rate of manipulation increased the most between weeks 8 and 9. At the same time, the most frequent targets of manipulation shifted from the infant's own body and the bodies of others to surfaces and inanimate objects in the cage. Large increases in the proportion of time in an Alert/active state and improvement in postural control also occurred at the end of the second month. The data suggest that major organizational changes in motor coordination and the regulation of behavioral state occurred jointly over a short period of time at about 8 weeks of age. In comparison to other species of monkeys, the capuchin infant displayed later development of manipulation, postural control, and independent locomotion, and greater dependence on social contacts for early interaction with its environment. These characteristics are in accord with the greater neurological immaturity of the capuchin infant at birth compared to other monkeys. PMID- 2925003 TI - Aggressive behaviors in adult rats deprived of playfighting experience as juveniles. AB - Matched litter mates were reared in one of three conditions: in pairs or in isolation with or without one hour of daily playfighting experience from 20 to 50 days of age. The rats were then regrouped within condition so that they lived with identically reared cagemates for a month. This regrouping eliminated the transient effects of isolation such as increased fearfulness. When tested as adults, there was no effect of early rearing condition on the probability of intraspecific aggression or muricide, although isolation-reared rats were less likely to retrieve the mice. However, isolation rearing reduced the latency to initiate shock-induced defensive aggression and increased both its frequency and intensity. Isolated animals which had been given daily playfighting during development did not show the effects of early social deprivation. The mechanisms through which playfighting experience shapes later defensive behavior remain to be determined. PMID- 2925004 TI - Measuring rates of sexual development in female Mongolian gerbils. AB - In previous experiments, we have shown that age at vaginal introitus predicts adult patterns of reproductive, maternal, and aggressive behavior of female Mongolian gerbils. In the present series of studies, we explored the relationship in gerbils between age at vaginal patency and three other indices of rate of female sexual development: ovarian weight, occurrence of vaginal estrus, and onset of attractiveness to males. We found that female gerbils, classified on the basis of their ages at vaginal introitus as early-maturing: (a) exhibited greater ovarian weights throughout development than did their late-maturing, female sibs; (b) exhibited estrus and Diestrus I stage vaginal smears and, by inference, ovulation at an earlier age than did late-maturing females; and (c) elicited mounting by males at an earlier mean age than did late-maturing females. The data were consistent with the hypothesis that age at vaginal introitus is a reliable indicator of rate of sexual development in female Mongolian gerbils. PMID- 2925005 TI - The quantitative relationship between nutritional effects on preweaning growth and behavioral development in mice. AB - Our objective was to establish whether nutritional effects on the behavioral development of preweaning mouse pups were linearly related to effects on body and brain growth or whether there was a threshold effect, with behavior being affected only by nutritional extremes. We also used a standardized scale of development to compare the relative magnitude of such effects on morphological and behavioral measures. The level of nutrient availability was manipulated continuously by rearing the pups in litter sizes ranging from 3 to 12. On Day 32 post-conception, measures were taken of body weight, brain weight, thickness of the cerebellar external granular layer (EGL), and behavioral development. The relationship between litter size and body weight, brain weight, and behavioral development was best described by a linear regression model; no threshold effect was apparent. By comparing measures on animals from different litter sizes at the same age (32 days) to standard developmental curves over a wide range of ages, we found that for every additional pup in a litter, body growth was retarded by the equivalent of 1.28 days, brain weight by 0.44 day, and behavioral development by 0.07 day. Although the variation in nutrient availability provided by this range of litter sizes does result in a linear relationship between growth and behavioral development, there is nevertheless considerable sparing of function. PMID- 2925006 TI - Coordinate decrease of tissue insulinlike growth factor I posttranscriptional alternative mRNA transcripts in diabetes mellitus. AB - In these studies, we examined the effect of excess levels of growth hormone (GH) on rat insulinlike growth factor I (IGF-I) gene expression in streptozocin induced diabetes mellitus. A solution hybridization/RNase protection assay was used to simultaneously quantitate the relative tissue content of the variant IGF I mRNA species arising from alternative splicing in the region encoding the COOH terminal extension E-peptide (IGF-Ia and IGF-Ib). IGF-Ia and IGF-Ib mRNAs were markedly decreased in liver, kidney, and lung tissues of diabetic rats. Although GF stimulates IGF-I gene expression, chronic GH excess from implanted somatomammotropic tumors did not appropriately induce tissue IGF-I mRNA content in diabetic animals. Treatment of diabetic rats with insulin for 1 wk restored basal and GH-stimulated IGF-Ia and IGF-Ib mRNA content toward that present in tissues of nondiabetic rats. The ratio of IGF-Ia to IGF-Ib mRNA remained relatively constant for each tissue and was not affected by the diabetic state, chronic GH hyperstimulation, or insulin therapy, suggesting that posttranscriptional splicing is not a regulated event in these conditions. Thus, both circulating IGF-I levels and tissue IGF-I gene expression are profoundly decreased in this model of experimental diabetes. Diminished tissue availability of IGF-I from endocrine and/or paracrine sources may be responsible for the growth retardation seen in uncontrolled diabetes mellitus. PMID- 2925007 TI - Proliferative retinopathy in NIDDM. Incidence and risk factors in Pima Indians. AB - The incidence of proliferative diabetic retinopathy was determined in the Pima Indians of the Gila River Indian Community in Arizona. Over 4 yr, this complication developed in 25 of 953 subjects greater than or equal to 9 yr of age with non-insulin-dependent diabetes. No cases were diagnosed in less than 35-yr old subjects, and the incidence was strongly related to the duration of diabetes. The cumulative incidence of proliferative retinopathy after 20 yr duration was 14%. All cases of proliferative retinopathy occurred in subjects with background retinopathy. Younger age at diagnosis of diabetes was associated with a higher incidence of proliferation when subjects with diabetes of similar duration were compared. A higher incidence of proliferative retinopathy, after controlling for age, sex, and diabetes duration, was associated with hypertension, proteinuria, renal insufficiency, absence of Achilles tendon reflex, elevated total serum cholesterol concentration, and insulin therapy. PMID- 2925008 TI - Diabetes, intermittent claudication, and risk of cardiovascular events. The Framingham Study. AB - The impact of diabetes on intermittent claudication was examined in 1813 men and 2504 women with 34-yr follow-up data in the Framingham study. For both sexes, diabetes was associated with a two- to threefold excess risk of intermittent claudication compared with its absence. A pronounced excess risk was also observed in subjects on oral hypoglycemic therapy and in women receiving insulin. Although diabetes was often associated with an atherogenic-risk profile, controlling for age and several concomitant risk factors failed to eliminate the association with intermittent claudication. Those who developed both intermittent claudication and diabetes were at an especially high risk of incident cardiovascular events. In women, the risk of coronary heart disease, stroke, and cardiac failure was increased 3-4 times when diabetes and intermittent claudication occurred together compared with when either condition existed alone. In diabetic men, the presence of intermittent claudication doubled the risk of stroke, and cardiac failure was approximately 3 times more likely in subjects with both conditions compared with either alone. We conclude that diabetes is an important risk factor for intermittent claudication, which in turn confers a serious prognosis for subsequent cardiovascular outcomes in the patient with diabetes. PMID- 2925009 TI - Structure-function relationship of the action of T-2 toxin on bovine platelets. AB - The effect of the trichothecene mycotoxin, T-2 toxin, on the ultrastructure of bovine platelets was investigated. In both toxin-treated and untreated platelets, the ultrastructure of the resting bovine platelet was characterized by the absence of an extensive open canalicular system and the appearance of granules and vacuoles which frequently impinged on the outer platelet membrane. No major ultrastructural changes were produced by T-2 toxin under conditions in which the platelet aggregation response was significantly inhibited. In bovine platelets exposed to the toxin, as in untreated platelets, there is evidence of pseudopod formation, indicating that T-2 toxin does not impair the initial response of platelets to stimulation. This observation is consistent with the companion function study which showed that, while T-2 toxin can impair both the rate and extent of aggregate formation, the most dramatic change is the relative instability of the platelet aggregates that form in the presence of the toxin. PMID- 2925010 TI - Suppression of humoral and cell-mediated immune responses by carbon tetrachloride. AB - The effects of carbon tetrachloride (CCl4), following 7 consecutive days of exposure ip at 500, 1000, and 1500 mg/kg, were determined on murine humoral and cell-mediated immune responses, body and organ weights, spleen cell blastogenesis following mitogenic stimulation, and clinical serum parameters for liver injury. In vivo sensitization of CCl4-treated B6C3F1 mice resulted in a dose-dependent suppression of the T-dependent antibody response to sheep red blood cells (sRBC) at all doses--36, 48, and 53%, respectively. The T-independent in vivo antibody response to DNP-Ficoll was suppressed only at 1500 mg/kg, and only by approximately 16%. This dosing regimen also resulted in a significant decrease in thymus weights; however, there were no significant effects on liver, kidney, lung, or body weights. The serum chemistry profile indicated a dose-dependent increase in serum glutamic-pyruvic transaminase (SGPT) levels (34-, 47-, and 55 fold) and a non-dose-dependent increase in serum bilirubin and total protein. Serum glucose and albumin levels were unaffected. Splenocytes from mice treated with 1500 mg/kg and sensitized in vitro with antigen demonstrated a comparably suppressed antibody response to the antigens sRBC and DNP-Ficoll as observed in vivo--66 and 28% respectively. This dose of CCl4 had no effect on the in vitro antibody response to the polyclonal antigen lipopolysaccharide. The mixed lymphocyte response was dose dependently suppressed following CCl4 exposure; however, the delayed-type hypersensitivity response was unaffected. Lymphocyte blastogenesis following mitogenic stimulation with lipopolysaccharide or concanavalin A was also inhibited by CCl4 exposure. These studies demonstrate that exposure to CCl4 results in a marked suppression in both humoral and cell mediated immune responses at concentrations which also affect the liver as evidenced by the marked increase in SGPT levels. PMID- 2925011 TI - Investigations of amitraz neurotoxicity in rats. III. Effects on motor activity and inhibition of monoamine oxidase. AB - The formamidine pesticide amitraz (AMZ) produces many behavioral and physiological changes in rats. We examined the dose effect and time course of AMZ on motor activity, monoamine oxidase (MAO) activity, and acetylcholinesterase (AChE) activity to evaluate possible neurochemical mechanisms for the behavioral effects of AMZ. For motor activity studies, male Long-Evans hooded rats were tested in photocell activity measurement devices. AMZ produced dose-related decreases in motor activity of rats allowed free access to food and rats maintained at a stable body weight through food restriction. Lowest effective doses of AMZ tested were 1-3 mg/kg, administered 20 min before testing. AMZ appeared to be about three times more potent in food-restricted rats, indicating that amount of body fat may play a significant role in the pharmacokinetics of AMZ. Motor activity returned to control levels over 4-5 days after dosing with 100-200 mg/kg AMZ, whereas recovery was evident the day after administration of low doses (1-30 mg/kg). Inhibition of MAO was measured in whole brain of rats sacrificed at various times after dosing with AMZ. Only greater than or equal to 100 mg/kg AMZ inhibited MAO, which was measurable within 2 hr of dosing and lasted up to 7 days. AMZ appeared to be more selective for type B MAO when given in vivo, although MAO-A was also inhibited at doses greater than or equal to 300 mg/kg. However, no selectivity was indicated by the IC50 values determined in vitro (IC50 = 31 and 28 microM for MAO-A and MAO-B, respectively). AMZ produced only negligible inhibition of AChE at the highest doses administered in vivo or at 10 mM in vitro. These data indicate that while AMZ does inhibit MAO, the dose range over which it produces this action is much higher than that which suppressed motor activity. Thus MAO inhibition is probably not responsible for AMZ-induced alterations in motor activity. PMID- 2925012 TI - 1,3-dichloropropene: two-generation inhalation reproduction study in Fischer 344 rats. AB - This study evaluated the effects of inhaled technical-grade 1,3-dichloropropene (DCPT) on reproduction and neonatal growth and survival. Groups of 30 male and 30 female Fischer 344 rats, approximately 6 weeks of age, were exposed via inhalation to 0, 10, 30 or 90 ppm DCPT for 6 hr/day, 5 days/week, for two generations. The parental f0 and f1 generations were each bred twice. Reproductive and neonatal parameters evaluated included indices of fertility and pup survival, gestation length, litter size, pup body weight, and pup sex ratio. Gross and histologic examinations were concluded on all f0 and f1 adults. In addition, randomly selected f1b and f2b weanlings were given gross examinations. Parental effects were limited to rats exposed to 90 ppm DCPT and included decreased body weights and histopathologic effects on the nasal mucosa of adult male and female rats. The histopathologic effects consisted of slight, focal hyperplasia of the respiratory epithelium and/or focal degenerative changes in the olfactory epithelium. No adverse effects on reproductive parameters or neonatal growth or survival were observed in the f1a, f1b, f2a, or f2b litters even at an exposure concentration which produced effects in adult animals. Based on these results, it is concluded that inhalation exposure of rats up to 90 ppm DCPT for two successive generations did not adversely affect the reproductive and neonatal parameters evaluated. PMID- 2925013 TI - Bioavailability of aluminum from drinking water. AB - Aluminum, present in our drinking water as hydroxide or sulfate, is limited by solubility to 2.5 mg/liter at pH 7.0. This study was carried out to determine if aluminum at doses typically found in drinking water would accumulate in rat tissues if a ligand such as citrate at neutral or acid pH is coadministered, or in the absence of citrate at acid pH. Al(OH)3 or AlCl3 was given ad libitum in drinking water to male Sprague-Dawley rats at 0, 0.1, 2.0, or 100 mg/liter, in 4 mM acetate, pH 3.2 (A), 4 mM citrate, pH 2.6 (C), 4 mM citrate, pH 7.0 (7C), or distilled water, pH 7.0 (W). After 10 weeks, rats were killed and tissues were wet-ashed in nitric acid for determination of aluminum by flameless atomic absorption. Copper, iron, and zinc were determined by flame atomic absorption. Metal ion concentrations in tibia, brain, liver, blood, and kidney did not differ significantly between treatment groups. Aluminum accumulated in intestinal cells of all 100 mg Al/liter rats, with the C group accumulating more aluminum than the A or W groups. In the C group, intestinal aluminum content increased significantly in a dose-dependent manner. Intestinal iron was decreased significantly in all the 100 mg Al/liter groups. Intestinal copper was decreased in the W group at 100 mg Al/liter, with a trend toward a decrease in A and C groups. We conclude that at these low levels studied, aluminum accumulates in intestinal tissue, and that this accumulation is enhanced by citrate ligand. At 100 mg Al/liter, intestinal iron accumulation is decreased, and copper accumulation is marginally decreased. PMID- 2925014 TI - Increased kidney glucose utilization induced by cyclosporine: lack of relation to magnesium excretion. AB - Cyclosporine enhances D-[5-3H]glucose utilization in homogenates of rat kidney medulla but not kidney cortex or liver. This is true whether cyclosporine is added to fresh tissue homogenates or is given to rats prior to sacrifice. Through the use of isolated perfused rat kidneys, an attempt was made to relate increased glucose utilization by cyclosporine to a possible consequence of cyclosporine nephrotoxicity, viz., loss of magnesium in urine. Although an enhanced rate of glucose utilization by cyclosporine was evident in isolated kidneys, glucose consumption was not related to urinary magnesium loss. In fact, kidneys from cyclosporine-treated rats actually showed a normal or even diminished urinary magnesium loss. The data suggest that cyclosporine-induced magnesium imbalance may be extrarenal in origin and that the kidney medulla may be a primary site of the nephrotoxic action of cyclosporine since the drug increases glucose utilization at this site. PMID- 2925015 TI - Hepatotoxicity of agents that enhance formation of focal hepatocellular proliferative lesions (putative preneoplastic foci) in a rapid rat liver bioassay. AB - The histopathology of hepatic toxicity for 58 chemicals previously tested in a rapid rat liver bioassay for demonstrating potential hepatocellular carcinogens and/or tumor promoters was reviewed. Rats received the test diet for 1 week prior to partial hepatectomy and for an additional 5 weeks thereafter at doses near the estimated maximally tolerated dose. These rats served as controls for others receiving initiation by N-nitrosodiethylamine (DEN) and the test diets. Twenty two of these chemicals were previously found to enhance the formation of glutathione S-transferase, placental form (GST-P)-positive putative preneoplastic hepatocellular foci (promoters) following DEN initiation in this rapid bioassay, whereas 36 chemicals did not. Of the agents that promoted GST-P-positive foci, 14/22 (63.6%) produced toxic hepatocyte lesions while only 4/36 (11.1%) of the nonpromoters did so at the doses used. Biliary toxicity was found for 7/22 (31.8%) of the promoters and 6/36 (16.7%) of the nonpromoters. Only 2/13 (15%) chemicals that inhibited GST-P-positive foci produced hepatic toxicity. Thus, agents that were presumed hepatic tumor promoters characteristically were hepatotoxins while nonpromoters of carcinogenesis were not hepatotoxins in this rapid rat liver bioassay. PMID- 2925016 TI - Pharmacokinetics of methylmercury in the blood of monkeys (Macaca fascicularis). AB - Statistical analysis of the blood mercury profiles of groups of two and four adult female cynomolgus monkeys (Macaca fascicularis) given single oral doses of 500 micrograms and 50 microCi (25.3 micrograms) methylmercury/kg body wt, respectively, indicates that a two-compartment model best describes the absorption and elimination of methylmercury in blood. Absorption was largely complete within 6 hr, and the half-time of methylmercury during the terminal elimination phase ranged from 10 to 15 days. In addition, three groups of five adult female cynomolgus monkeys were dosed with methylmercury every Monday, Wednesday, and Friday for periods up to 2 years at effective doses of 10, 25, or 50 micrograms methylmercury/kg body wt/day. The average blood levels at steady state were estimated to be 0.27 +/- 0.02, 0.69 +/- 0.03, and 1.51 +/- 0.08 ppm, respectively, with average time taken to achieve 95% of the steady-state blood level being about 92 days. The steady-state blood levels obtained via extrapolation of the results from the two single-dose experiments were significantly different from those actually achieved, indicating that the average steady-state blood levels under chronic dosing conditions may not be accurately estimated on the basis of short-term experiments. The data were also used to examine the impact of different dosing intervals on variation in blood mercury levels. PMID- 2925017 TI - Absence of liver DNA fragmentation in rats treated with high oral doses of 32 benzodiazepine drugs. AB - Literature data on mutagenic-carcinogenic activity of benzodiazepines are scarce, restricted to few of them, and contradictory. Consequently, in order to provide additional information for the assessment of the genotoxic risk connected with the use of this family of drugs, 32 benzodiazepines of various chemical structure have been tested for their capability to induce DNA damage in vivo, which is considered a sensitive index of potential mutagenic-carcinogenic activity. The frequency of DNA single-strand breaks and/or alkali-labile sites was checked in the liver of rats given orally a single dose (1 mmol/kg) or 15 successive daily doses (0.2 mmol/kg) by the use of a new viscometric technique capable of detecting one DNA lesion per 10(10) Da. Statistically significant changes of viscometric parameters indicative of liver DNA fragmentation were absent with all 32 benzodiazepines, after both acute and subacute treatments. Since the doses tested in rats were from 100 to more than 5000 times higher than doses usually administered to humans, these negative results are in favor of the absence of mutagenic-carcinogenic effects in patients taking benzodiazepines. PMID- 2925018 TI - Disruption of auditory function by acute administration of a "room odorizer" containing butyl nitrite in rats. AB - Butyl nitrite is the predominant and presumed active ingredient in a variety of commercial preparations sold as "room odorizers." These compounds have significant abuse potential, giving the user the sensation of a "rush", which may be related to their intense cardiovascular effects. The pharmacological properties of butyl nitrites are similar to those of amyl nitrite which is also abused for its psychological effects, but whose availability is limited by prescription for treatment of angina. A significant body of literature suggests that the inner ear is vulnerable to acute hypoxic exposure. Since butyl nitrite induces high levels of methemoglobin and also reduces blood pressure due to peripheral vasodilation, we hypothesized that this compound might produce auditory dysfunction. We studied the effect of acute exposure to a butyl nitrite "room odorizer" on 10- and 40-kHz auditory function in rats. A loss in auditory sensitivity was found at both frequencies on the day following administration of the compound. Auditory dysfunction tended to subside over the next several days at 40 kHz, although a significant loss of sensitivity for tones of 10 kHz was observed over a 6-day period after administration of the agent. Methemoglobin levels measured in rats of the same age were elevated significantly 30 and 60 min after butyl nitrite to levels of 30-45%. Methemoglobin levels were found to be normal 18 hr after administration when the first audiometric tests were conducted. The data suggest that auditory function in the middle of the rats' auditory range, 10 kHz, was disrupted for a longer period than was high-frequency (40 kHz) auditory function. PMID- 2925019 TI - Inhalation fertility and reproduction studies with O,O' dimethylphosphorodithioate in Sprague-Dawley rats. AB - Groups of 15 male and 35 female Sprague-Dawley rats were exposed to O,O' dimethylphosphorodithioate (DMPDT) 6 hr/day, 5 days/week for 11 weeks. Initial target concentrations were 0, 4, 25, and 200 mg/m3. However, because of excessive toxicity, the high-exposure level was reduced to 125 mg/m3 after 8 weeks. Exposed males were cohoused with two unexposed females immediately following the exposure period and later mated to an additional two unexposed females following a 16-week recovery period. Exposed females were cohoused with untreated males, and exposures were resumed after mating and continued during gestation. Some females were terminated at midgestation to assess fertility, while others were allowed to deliver their pups. F1 animals were terminated for histological examination or mated to assess fertility. High-exposure level F0 males were infertile after exposures, and there was little or no recovery. The fertility of low-exposure level males was not affected, but equivocal results were obtained at the mid exposure level. In this study, testicular lesions were observed only in high level F0 males. However, testicular lesions were also noted in a few males exposed to 4 and 25 mg/m3 in a concurrent subchronic toxicity study. Female fertility was apparently unaffected by exposure, and no treatment-related effects were noted in males or females exposed in utero. PMID- 2925020 TI - Dermal absorption of phthalate diesters in rats. AB - This study examined the extent of dermal absorption of a series of phthalate diesters in the rat. Those tested were dimethyl, diethyl, dibutyl, diisobutyl, dihexyl, di(2-ethylhexyl), diisodecyl, and benzyl butyl phthalate. Hair from a skin area (1.3 cm in diameter) on the back of male F344 rats was clipped, the [14C]phthalate diester was applied in a dose of 157 mumol/kg, and the area of application was covered with a perforated cap. The rat was restrained and housed for 7 days in a metabolic cage that allowed separate collection of urine and feces. Urine and feces were collected every 24 hr, and the amount of 14C excreted was taken as an index of the percutaneous absorption. At 24 hr, diethyl phthalate showed the greatest excretion (26%). As the length of the alkyl side chain increased, the amount of 14C excreted in the first 24 hr decreased significantly. The cumulative percentage dose excreted in 7 days was greatest for diethyl, dibutyl, and diisobutyl phthalate, about 50-60% of the applied 14C; and intermediate (20-40%) for dimethyl, benzyl butyl, and dihexyl phthalate. Urine was the major route of excretion of all phthalate diesters except for diisodecyl phthalate. This compound was poorly absorbed and showed almost no urinary excretion. After 7 days, the percentage dose for each phthalate that remained in the body was minimal and showed no specific tissue distribution. Most of the unexcreted dose remained in the area of application. These data show that the structure of the phthalate diester determines the degree of dermal absorption. Absorption maximized with diethyl phthalate and then decreased significantly as the alkyl side chain length increased. PMID- 2925021 TI - Acetaminophen and p-aminophenol nephrotoxicity in aging male Sprague-Dawley and Fischer 344 rats. AB - Strain differences in susceptibility of rats to acetaminophen (APAP)-induced nephrotoxicity have been reported previously. Young adult male Fischer 344 (F344) rats are susceptible, whereas weight-matched Sprague-Dawley (SD) rats are not susceptible to APAP nephrotoxicity. Susceptibility to APAP nephrotoxicity is also age dependent, at least in F344 rats. Middle-aged (12-15 months old) male F344 rats are more susceptible to APAP-induced nephrotoxicity than are young adult (2 4 months old) males. APAP nephrotoxicity in aging SD rats has not been evaluated. The present studies were designed to define strain differences in the nephrotoxicity of APAP and p-aminophenol (PAP), a nephrotoxic metabolite of APAP, using 2-, 3-, and 9- to 12-month-old F344 and SD rats. At 2 months of age, F344, but not SD, rats were susceptible to APAP-induced nephrotoxicity. However, at 3 months of age, strain differences were less marked, as susceptibility to APAP nephrotoxicity appeared to increase between 2 and 3 months of age only in SD rats. By 9-12 months of age, susceptibility to APAP nephrotoxicity was comparable in F344 and SD rats. No age- or strain-related differences were observed in the excretory pattern of urinary APAP and metabolites that might explain the increased susceptibility of aging rats to APAP nephrotoxicity. Strain differences in age-matched rats were not marked for PAP-induced nephrotoxicity. Susceptibility of both 3- and 12-month-old F344 and SD rats to PAP-induced nephrotoxicity was greater compared to strain-matched 2-month-old rats. In both F344 and SD rats, PAP nephrotoxicity increased only modestly between 3 and 12 months of age, indicating that increased susceptibility to PAP probably does not play a major role in the age-dependent increase in APAP nephrotoxicity. Thus, strain differences in APAP nephrotoxicity decrease with advancing age. The mechanisms mediating the increased susceptibility to APAP nephrotoxicity in middle-aged rats are not known but may relate, at least in part, to age-dependent differences in pharmacokinetics. The present study highlights the importance of considering the age of rats when evaluating drug toxicity. Even in young adult rats, subtle maturational changes in drug metabolism and/or disposition may occur, making toxicological evaluation in weight-matched rats of different strains and ages inappropriate. PMID- 2925022 TI - A dose-response analysis of methoxychlor-induced alterations of reproductive development and function in the rat. AB - In the present study rats were dosed from weaning, through puberty and gestation, to Day 15 of lactation with methoxychlor at 25, 50, 100, or 200 mg/kg/day. Morphological landmarks of puberty were measured, including the ages at vaginal opening, first estrus, and first estrous cycle in females and at preputial separation in males. In the female, estrous cyclicity, fertility, litter size, number of implantation sites, organ weights, and ovarian and uterine histology were also measured. The viability of the offspring (F1) and their fertility were evaluated using a continuous breeding protocol. Males were necropsied after breeding, the reproductive organs were weighed, and the cauda epididymal sperm counts were determined. One testis was used for histopathology, while the other was used to quantify interstitial fluid (IF) content, IF testosterone concentration, and testicular sperm production. Testosterone and androgen-binding protein were measured in the caput epididymis, and sperm motility and morphology were evaluated from a caudal sample. The serum and pituitary were saved for hormonal determinations. Methoxychlor accelerated the age at vaginal opening and first estrus, and the vaginal smears were cornified. Growth was retarded at 100 and 200 mg/kg/day and fertility was reduced when the females were bred with untreated or similarly treated males. In the highest-dose group, the mated females went from constant estrus into pseudopregnancy following mating, but they had no implants. In males, methoxychlor treatment markedly reduced growth, seminal vesicle weight, cauda epididymal weight, caudal sperm content, and pituitary weight. Puberty was delayed in the two highest-dosage groups. Testicular sperm measures were much less affected than caudal measures. Testis weight and histology were slightly affected, and testicular sperm production, sperm morphology, and motility were unaffected. Endocrine function of the testes and pituitary was altered by methoxychlor administration. Leydig cell testosterone production, in response to human chorionic gonadotropin challenge, was reduced and pituitary levels of prolactin, thyroid-stimulating hormone (TSH), and follicle-stimulating hormone (FSH) were altered. In contrast, serum levels of prolactin, FSH, and luteinizing hormone were unaffected. Serum TSH was reduced by 50% of control at 100 and 200 mg/kg/day, while pituitary levels were increased. Gonadotropin-releasing hormone concentration in the mediobasal hypothalamus was also elevated. In spite of the many reproductive alterations, the fertility of treated males was not reduced when they were mated with untreated females.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2925023 TI - Church or sect? The counterculture 10 years later. PMID- 2925024 TI - Family medicine as counterculture. PMID- 2925025 TI - Oxytocin and the induction of labor: use in a network of community hospitals. AB - This study uses a matched cohort design to compare the process and outcome of patients whose labor was induced using oxytocin with those entering labor spontaneously in a network of small community hospitals. The patients with induced labor more frequently had an arrest of dilatation and had infants who showed more abnormalities of fetal heart rate. There were no differences in infant APGAR scores. The previously reported increases in epidural anesthesia, episiotomy, and assisted deliveries in patients with induced labor were not found, suggesting a significantly different style of care provided by family physicians in small community hospitals. PMID- 2925026 TI - Combined training in procedural and behavioral counseling skills. AB - A combined training experience in behavioral counseling skills and office procedural skills was developed for second-year family medicine residents. Residents were relieved of other clinical responsibilities during the month this curriculum was presented, thus avoiding problems of competition for the residents' attention. By having all second-year residents together, faculty teaching time was efficiently used, and the haphazard results from relying on faculty-resident precepting experiences in the family practice center to provide training in these areas was avoided. Behavioral counseling and office procedural skills training were found to be complementary in areas of content, in teaching methods, and in maintaining variety and interest in the training experience. Pre- and post-testing of residents revealed a significant increase in knowledge of cognitive aspects of these two content areas at the end of the experience. PMID- 2925027 TI - Continuity of care and outcome in nursing home patients transferred to a community hospital. AB - This study prospectively investigated the effect of continuity of primary physician care on functional ability and outcome of nursing home patients transferred to a community hospital. Evaluated were 335 consecutive transfers with concurrent chart review and a standardized functional rating scale on admission and discharge from the hospital. Continuity of care by the primary physician was more likely with a greater length of stay. There was no association of continuity with age, sex, initial functional status or mental status of the patient, type of admission, or payment source. No significant relationship was found between outcome and continuity of care by the primary physician. Logistic regression analysis indicated that emergency admission to the hospital conferred an increased risk of mortality but that the level of primary physician continuity did not. PMID- 2925028 TI - Factors influencing student selection of family practice residency programs in Texas. AB - This study identified the relative influence of eight major factors on students' selections of family practice residency programs in Texas. All students (127) selected through the National Residency Matching Program in 1987 by 22 residency programs in Texas were surveyed. Based on a 91% response rate, 52 rating scale items were subjected to exploratory and confirmatory factor analyses. The resulting eight factors were rank ordered according to program type (eg, medical school based) based on mean scores of items that loaded on each factor. The factor most influential in students' selections of programs was the "quality of training" they perceived they would receive, while the least important factor was "resident compensation and benefits." Students who selected medical school based programs and community based, medical school affiliated programs differed significantly as to the importance they placed on the "academic orientation of the program" and the "attitude toward family physicians" in their program selections. PMID- 2925029 TI - Specialty choice by medical students: recent graduate follow-up survey at the University of Washington. AB - Understanding the factors that contribute to specialty choice by medical students is crucial if the proportion of physicians in primary care is to be increased. We surveyed 1,182 graduates of the University of Washington (1978-84) inquiring about residency training, current clinical specialty, influences and attributes in specialty selection, satisfaction with current specialty, and timing of the decision. Usable responses were 56% of the total surveyed (67% without 194 undeliverable surveys). When rates of non-response, bad address, and usable response were compared across graduating classes, no significant differences were found. The data also do not overrepresent a particular training choice or specialty group compared to all graduates. The majority of respondents (n = 404, 62.3%) were in practice at the time of the survey. The distribution of specialty groups was significantly different for those in practice compared to those still in training (X2 = 27.28, P less than .001). Although the groups were somewhat different, these differences did not lead to major changes in responses. Sixty percent of graduates choosing family medicine did so either before or during the first two years of medical school. This contrasts with other specialties, where the majority of students did not make a decision until the third year of medical school. Medical school courses were an important influence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2925030 TI - Entry of U.S. medical school graduates into family practice residencies: 1988 1989 and eight-year summary. AB - This study continues a series of reports from the American Academy of Family Physicians on the percentage of each medical school's graduates who enter family practice residency programs. Approximately 10.7% of the 15,947 graduates of United States medical schools between July 1987 and June 1988 were first-year residents in family practice in October 1988. This compares to 12.0% in the previous year. The Mountain region reported the highest percentage of medical school graduates who are first-year residents in family practice programs in October 1988; the Middle Atlantic and New England regions had the lowest percentages. Medical school graduates from publicly funded medical schools were twice as likely to be first-year residents in family practice in October 1988 as were graduates from privately funded medical schools. The percentages for each medical school have varied substantially from year to year in the eight years that the AAFP has reported this information. The average percentage for each medical school for the last eight years, as well as the cumulative percentage for each medical school, are reported. Although school-specific percentages may show wide year-to-year variations, the total percentage of U.S. medical school graduates entering family practice residencies has been generally stable near 12.0% in the previous seven years. The decline to 10.7% for 1987-88 is cause for careful review. PMID- 2925031 TI - Alcoholics anonymous in medical school education. AB - The Department of Family and Community Medicine at Eastern Virginia Medical School has implemented a program introducing second-year medical students to Alcoholics Anonymous. This report reflects the results of the students' experience. All students felt they would be able to use Alcoholics Anonymous more effectively in caring for their patients. PMID- 2925032 TI - Thanks for 'call to arms'. PMID- 2925033 TI - Training for general practice: a look to Norway. AB - In the 1960s general practitioners were a dying race in Norway. Today general practice is a highly approved specialty among doctors as well as patients. Better education is one of the revitalizing factors. General practice is currently taught as a mandatory subject at all four universities in Norway. The practice apprenticeship is the essential element in our undergraduate curricula. In their fifth year, the students spend three to eight weeks in a structured training program supervised by general practice faculty. Approximately 500 general practitioners take part in this decentralized training network. In 1985 general practice was recognized as a specialty in Norway. The obligatory requirements in the five-year educational program are: -courses, 400 hours -hospital training, one year -general practice training, four years -group-based training program, two years The last element is based on a decentralized concept where a group of two to 10 trainees meet for three hours every two weeks during a two-year period. The group is headed by an appointed and qualified trainer. Besides being in accordance with the geography and demography of Norway, this model gives substance to the slogan "general practice can only be learnt in general practice." PMID- 2925034 TI - Teaching the tension: residency programs and cost containment. PMID- 2925035 TI - [Thalidomide and ulcerative colitis in Behcet's disease]. PMID- 2925036 TI - [Hemolytic anemia and ulcerative rectocolitis: splenectomy or coloproctectomy?]. PMID- 2925037 TI - [Anorectal Buschke-Lowenstein tumor (giant condylomatosis) requiring amputation of the rectum]. PMID- 2925038 TI - [Pancreatic mucinous cystadenocarcinoma with a rapidly fatal course]. PMID- 2925039 TI - [Ischemic colitis during an unusual effort]. PMID- 2925040 TI - Campylobacter pylori, hypertrophic erosive gastritis and hypoalbuminemia healed by cephalexin therapy. PMID- 2925041 TI - The role of amino acid decarboxylase in the stimulation of gastrin release in man. AB - As amino acid-induced gastrin release is dependent on amino acid decarboxylase activity in rat, we examined the gastrin response to intragastric phenylalanine before and after treatment with carbidopa in 12 healthy male volunteers; carbidopa is an inhibitor of aromatic amino acid decarboxylation. Our results showed no significant difference between the pre- and postcarbidopa periods in the same subjects, suggesting that decarboxylation is not a necessary step for amino acids to stimulate G-cells in man. However, carbidopa seems to have an inhibitory effect on gastrin release, independently of its action on decarboxylase activity. PMID- 2925042 TI - [The symptom index: progress in the analysis of esophageal pH metry]. AB - Commercially available pH-monitoring systems include one or more event markers which should allow correlation between reflux episodes and symptoms. However, the clinical relevance of this feature has not yet been thoroughly investigated. In this prospective study, we attempted to establish whether the use of an event marker could improve the accuracy of intraesophageal pH-monitoring and if a correlation between symptoms, as detected by event markers and esophageal exposure to acid could be shown. One hundred seven patients were studied. Only 47 p. 100 used the event marker during 24 h pH-metry. There was no statistical significance in the incidence of gastroesophageal reflux (GER i.e. time spent below pH 4 greater than 4.2 p. 100), age and socioeconomic status between patients who used the marker and those who did not. A concordance index was calculated by dividing the number of reflux episodes associated with a marked event by the total number of marked events. In 50 p. 100 of the 16 patients who used the marker and had GER, the concordance index was greater than 75 p. 100. On the contrary, only 4 out of 35 patients without GER had a concordance index greater than 75 p. 100 (p less than 0.003). Finally, the index was less than 25 p. 100 in 4 patients with GER and in 22 without GER (p less than 0.02). The lowest pH reached within the esophagus was virtually identical during all the reflux episodes, regardless of marker pressing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2925043 TI - [The liver, hepatobiliary infections and antibiotics]. PMID- 2925044 TI - [Serum activity of mitochondrial aspartate aminotransferase and extrahepatic cholestasis]. AB - Serum mitochondrial aspartate aminotransferase (mAST) level and the mitochondrial aspartate aminotransferase/total aspartate aminotransferase ratio (mAST/AST) have been proposed as sensitive markers of chronic alcoholism. Their specificity, however, remains poorly defined. The purpose of this study was to compare these markers in three groups of hospitalized patients: group I, 80 patients with chronic alcoholic liver disease; group II, 51 patients with chronic liver disease without alcoholism; group III, 44 patients with extrahepatic cholestasis (due to choledocholithiasis in 21 and malignant in 23). mAST was measured after immuno precipitation of cytoplasmic aspartate aminotransferase. The normal values of mAST (less than or equal to 2 mu/l) and mAST/AST (less than or equal to 6 p. 100) were defined in a group of 59 non alcoholic subjects without liver disease (controls). mAST was increased as compared with controls in 91 p. 100 of the patients of group I, 20 p. 100 of group II, 61 p. 100 of group III. mAST was comparable in groups I (mean +/- SD: 10 +/- 10.8) and III (10.3 +/- 12.9), and higher than in group II (1.8 +/- 2.4). m/AST was increased in 59 p. 100 of the patients of group I, 6 p. 100 of group II and 36 p. 100 of group III. It was higher in group I (8 +/- 4 p. 100) than in group III (6 +/- 4 p. 100, p less than 0.02), and particularly higher in both these groups than in group II (2 +/- 1 p. 100, p less than 0.00001). mAST was correlated to AST in each of these three groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2925045 TI - [Hepatotoxicity of drugs. Update of the data bank on hepatic involvement and the responsible drugs]. PMID- 2925046 TI - [A case of chronic ischemic erosive gastropathy healed after surgical revascularization]. AB - A case of chronic ischemic erosive gastropathy secondary to chronic abdominal vascular insufficiency is reported. This gastropathy healed after revascularization procedure but then recurred after stenosis of the aortomesenteric graft. The clinical picture was characterized by post-prandial abdominal pain, weight loss and an abdominal bruit. The upper gastrointestinal endoscopy showed multiple non hemorrhagic antral erosions with irregular outlines and a pseudomembranous floor. Reduction of the resistance of the gastric mucosal barrier by a chronic decrease of mucosal blood flow probably accounted for the gastric erosions. Although the prevalence is unknown, ischemic injury to the stomach is unexpected, because of the rich collateral circulation of this organ. Increased awareness of the disease and its prognostic implications should lead to suggest abdominal vascular insufficiency based on their clinical and gastroscopic aspects, thus leading to operation before acute mesenteric infarction occurs. PMID- 2925047 TI - A sensitive and specific serologic test for detection of Campylobacter pylori infection. AB - Campylobacter pylori has been associated with gastritis, duodenal ulcer, gastric ulcer, and nonulcer dyspepsia. Evidence that C. pylori may be the causative agent or at least a major contributory factor in peptic ulcer disease has generated intense interest in the development of reliable methods for detecting C. pylori infections. We have developed a specific and sensitive enzyme-linked immunosorbent assay (ELISA) that detects serum immunoglobulin G antibodies directed against high molecular weight cell-associated proteins (HM-CAP) of C. pylori. In a blinded fashion we tested sera from 300 individuals and found that all of 147 HM-CAP ELISA-negative individuals were also negative for C. pylori, as documented by a negative urea breath test; also, 151 of 153 C. pylori-positive (by urea breath test) individuals were HM-CAP ELISA-positive. Campylobacter pylori was cultured from the two ELISA-negative but infected patients and these isolates did possess HM-CAP antigens, showing that these two individuals had failed to seroconvert. Thus, the specificity and positive predictive value of the HM-CAP ELISA were each 100%; the sensitivity of the assay was 98.7%, and the negative predictive value was 98.6%. The HM-CAP ELISA and the urea breath test both proved valuable for detecting C. pylori infection, the urea breath test being a more direct method whereas the ELISA is less expensive and easier to perform. Furthermore, the results of a serologic test such as the HM-CAP ELISA would not be influenced by recent ingestion of bismuth compounds or antimicrobial therapy, which might suppress C. pylori and cause a transient false-negative result in the urea breath test. PMID- 2925048 TI - Familial empiric risk estimates of inflammatory bowel disease in Ashkenazi Jews. AB - Genetic factors have been implicated in the etiology of inflammatory bowel disease (IBD) because of the increased occurrence of IBD in relatives. To further characterize the familial aggregation of IBD, we obtained family histories by interview on 188 IBD patients, including 154 Ashkenazi Jews (82%), ascertained through a Los Angeles gastroenterology practice. Thirty-three index cases (17.6%) had at least one affected first-degree relative; an additional 11 had more distant affected relatives. Thus, 23.4% of our sample had a positive family history. The quantification of empiric risk estimates for various classes of relatives has been quite limited and has been reported in only a few series. An important goal of our study was the determination of the specific empiric risk figures for relatives. We obtained uncorrected risk estimates of 2.5% to off spring, 5.2% to siblings, and 2.9% to parents. Although the highest risk we observed is to siblings, IBD has a variable and often late age of onset, and it is likely that many relatives, particularly offspring, of patients in this sample have not reached the age at which they will manifest clinical disease. Thus, these uncorrected risks as well as those reported in the literature are an underestimate of the true empiric risks. To provide an estimate of the true lifetime risks, we utilized age-specific incidence data to calculate the following age-corrected empiric risk estimates for IBD: 8.9% to offspring, 8.8% to siblings, and 3.5% to parents. It is these latter age-corrected estimates that are most appropriate for both genetic counseling and genetic modeling. PMID- 2925049 TI - Human myenteric plexus: confirmation of unfamiliar structures in adults and neonates. AB - To define the myenteric plexus along the human gastrointestinal tract, we studied three neonatal and six adult specimens, postmortem, by silver impregnation. There were no clear differences between the neonatal and the adult gastrointestinal tracts. In the body of the esophagus, the plexus was sparse, with few ganglia; 30%-40% of fascicular intersections were devoid of ganglia. In the lower 5 cm, the esophagus had thick bundles of nerve fibers ("shunt fascicles"), which crossed the gastroesophageal junction and radiated to the periphery of the stomach through several branches. The plexus in the stomach was uniform, with intermediate and intrafascicular ganglia. A thick nerve bundle encircled the pylorus and gave branches on either side to the antrum and the duodenum. Shunt fascicles in the stomach did not cross the pylorus but extended to the distal antrum. In the duodenum and proximal jejunum, the plexus was regular, but in the mid-small intestine, the longitudinal interganglionic fascicles were more prominent than the circumferential fascicles. Distally, this pattern was reversed; circumferential fascicles were more prominent and ganglia were dense in the terminal ileum. Thin, short shunt fascicles were scattered along the entire small intestine, becoming more abundant in the terminal ileum. Short, thick shunt fascicles traveled proximally from the ileocecal junction for about 25-30 cm. As in the stomach, shunt fascicles did not cross the ileocecal junction, but a thick nerve bundle encircled it. In the cecum and proximal colon, the plexus was sparse with large intermediate and intrafascicular ganglia. In the rectum and distal colon, the plexus was dense, with parafascicular and intrafascicular ganglia. Long ascending nerves extended from the distal rectum into the midcolon. In addition, there were short, thick nerve bundles in the rectum that traveled proximally. PMID- 2925050 TI - Gastric endocrine cell behavior in Zollinger-Ellison patients upon long-term potent antisecretory treatment. AB - Serum gastrin and gastric endocrine cell numerical densities were examined in 22 patients with long-standing Zollinger-Ellison syndrome who were receiving either ranitidine, omeprazole, or other antisecretory drugs (SMS 201-995 or pirenzepine with or without ranitidine) for long periods of time. Fifteen patients had iterative biopsies. Twenty-one subjects with normal endoscopy, serum gastrin, and acid secretion served as controls. Individual fundic argyrophil cell density was above the highest control value in 77% of the patients, whatever the treatment. Argyrophil cell densities tended to be higher in women than in men. During the survey, fundic carcinoids developed in one ranitidine- and in one omeprazole treated patient. Fundic argyrophil cell densities were correlated with serum gastrin levels (r' = 0.730, p less than 0.001). Antral somatostatin cell density was not modified in any patients as compared with controls, nor was antral gastrin cell density except in omeprazole-treated patients. In these patients, gastrin cell density and gastrin to somatostatin cell ratio were significantly higher than in all other patients or controls. Such increases may indicate true gastrin cell hyperplasia in relation to drug-induced profound acid inhibition. PMID- 2925051 TI - Colonic and esophageal transepithelial potential difference in cystic fibrosis. AB - To evaluate differences in the expression of cystic fibrosis (CF) transport defects in the gastrointestinal tract of subjects with CF, in vivo measurements of colonic and esophageal transepithelial electrical potential difference (PD) were performed before and during amiloride superfusion in CF and healthy subjects. Esophageal PD before (-16 +/- 2 vs. -16 +/- 3 mV) and after (-14 +/- 2 vs. -15 +/- 0.3 mV) superfusion with amiloride were similar for CF and healthy subjects. Basal rectosigmoid colon PD was also similar (CF: mean -23 +/- 6 and maximal -37 +/- 9 mV; normal: mean -26 +/- 5 and maximal -45 +/- 11 mV) in both groups. However, with amiloride superfusion (10(-4) M) the colonic PD in CF subjects was almost abolished (95% +/- 15% inhibition), whereas the PD in healthy subjects was only partially reduced (42% +/- 6%) (p less than 0.05). The greater inhibition with amiloride in CF, which was evident in absolute terms (26 +/- 4 vs. 16 +/- 3 mV for controls, p less than 0.05) as well as relative terms, could not be ascribed to a difference in mineralocorticoid secretion rates, because 24 h urine excretion of aldosterone and 17 hydroxy and 17 ketosteroids were similar in both groups. Freshly excised colonic epithelia from 1 CF and 3 non-CF subjects were studied in Ussing chambers, and a similar difference in amiloride responsiveness noted: PD and short-circuit current declined 33% +/- 2% and 37% +/ 4%, respectively, in seven tissues from the colons of 3 patients without CF, whereas both PD and short-circuit current were fully inhibited (100%) in all three tissues from the CF patient. As the presence of an amiloride-insensitive component of short-circuit current in non-CF colon is largely due to electrogenic Cl- secretion, the demonstration that this component was absent both in vivo and in vitro in CF colon establishes the presence of a defect in electrolyte transport in CF colon, a defect consistent with recent reports of absent electrogenic Cl- secretion in CF intestine. PMID- 2925052 TI - Properties of rabbit pepsinogen granules. AB - Pepsinogen granules were isolated from the rabbit stomach using isoosmotic Percoll density gradients, low free calcium (10(-7) M), and conditions that minimize physical damage. These granules were enriched approximately eightfold with respect to pepsinogen and were free from contamination by mitochondria and endoplasmic reticulum. Electrophoretic examination shows pepsinogen to account for approximately 80% of the Coomassie Blue-stainable intragranular protein and the granule membrane to yield a simple spectrum of proteins similar to other granule systems. In addition to purity, the isolated granules displayed a high degree of osmotic stability at physiologic conditions of pH, temperature, and ionic strength. This stability suggests strict regulation of the granule electrolyte transport pathways, which are shown to include a Cl- conductance, Cl /anion exchange, and a K+ conductance. These transport systems in the granule membrane are consistent with the promotion of primary fluid secretion. Furthermore, granule-mediated ion transport would allow the chief cell to couple fluid secretion directly to exocytotic pepsinogen secretion and flush the enzyme from the base of oxyntic glands. PMID- 2925053 TI - Progastrin processing during antral G-cell hypersecretion in humans. AB - Using radioimmunoassays specific for essential processing sites of human progastrin in combination with chromatography before and after cleavage with trypsin and carboxypeptidase B, we have examined antral biopsy specimens and serum from 10 hypergastrinemic patients with fundic atrophic gastritis and 7 normal control subjects. Four types of processing were studied: N-terminal proteolysis (at the N-terminus of component I, gastrin 34, and gastrin 17); C terminal proteolysis (at the C-terminus of the amide donor, glycine93 in preprogastrin); alpha-carboxyamidation (of phenylalanine92); and O-sulfation (of tyrosine87). The results show that progastrin during permanent G-cell hypersecretion is less completely processed with respect to C-terminal proteolysis, alpha-amidation, and tyrosine-sulfation. In contrast, the degree of N-terminal proteolysis is normal. Thus, the processing of progastrin adjacent to the active site of gastrin is more restrictively controlled than N-terminal processing during G-cell hypersecretion associated with pernicious anemia. PMID- 2925054 TI - Characterization of estrogen receptor from human liver. AB - Characterization of the estrogen receptor in cytosol from human male liver was undertaken to further understanding of the molecular basis of estrogen action in this tissue. By analysis of estrogen binding data of crude cytosol, saturable estrogen binding showed a Kd = 4.7 X 10(-10) M. High levels of nonsaturable binding were also detected. The estrogen-binding activities detected could be distinguished by their steroid specificity, hydrodynamic parameters, ionic properties, and sensitivity to proteolytic attack. Our findings also confirmed that the moderate-affinity estrogen binders found in rodent liver cannot be detected in human tissue. We concluded that the properties of estrogen receptor of human liver cytosol allow its separation from nonsaturable estrogen-binding components. PMID- 2925055 TI - Reduction of portal pressure by isosorbide-5-mononitrate in patients with cirrhosis. Effects on splanchnic and systemic hemodynamics and liver function. AB - The results of a study to characterize the effects of the oral administration of isosorbide-5-mononitrate (Is-5-Mn), the active metabolite of isosorbide dinitrate, on portal hypertension in 23 patients with cirrhosis are reported. Patients received 20 mg of Is-5-Mn (n = 10), 40 mg (n = 9), or a placebo (n = 4). No significant changes were observed after the administration of the placebo. However, both doses of Is-5-Mn significantly reduced portal pressure, as evaluated by measurements of the hepatic venous pressure gradient. The fall in portal pressure averaged 10% after the 20-mg dose and 18% after 40 mg and was maintained for the 2 h of observation. Reduction of portal pressure was due to a decrease in the wedged hepatic vein pressure, with no changes in the free hepatic venous pressure. After the 20-mg dose, the decrease in portal pressure was associated with an increase in hepatic blood flow (16%), suggesting a fall in hepatic vascular resistance. However, after the 40-mg dose, a reflex splanchnic vasoconstriction elicited by the fall in arterial pressure (-19%) appeared to contribute to the greater reduction in portal pressure, as suggested by a significant decrease in azygos blood flow (-15%). These beneficial effects on portal pressure were not associated with adverse effects on liver function, as evaluated by measurements of the hepatic clearance of indocyanine green and the hepatic intrinsic clearance. Neither dose of Is-5-Mn caused significant changes in these quantitative parameters of liver function. These findings suggest that Is-5-Mn could be a potentially useful and safe agent in the treatment of portal hypertension. PMID- 2925056 TI - Functional and biochemical characterization of the human gallbladder muscularis cholecystokinin receptor. AB - Gallbladders removed at cholecystectomy are a potentially useful source of human receptor for the gastrointestinal peptide hormone cholecystokinin (CCK). Seven healthy gallbladders (removed incidentally at time of resection of hepatic metastases) and 50 diseased gallbladders were studied. Cholecystokinin radioligand binding to an enriched plasma membrane preparation from these tissues was shown to be rapid, reversible, temperature-dependent, saturable, specific, and high-affinity. Computer analysis of equilibrium binding data using the Ligand program best fit a single class of binding sites with Kd = 1.0 +/- 0.1 nM (mean +/- SEM). This was similar in health and disease, with no apparent differences related to age, gender, or body habitus. The structural specificity for binding to this site correlated well with relative potencies for CCK-gastrin peptides to stimulate gallbladder contraction. To biochemically characterize this receptor, we used a battery of reagents, including "long" (125I-Bolton Hunter-CCK-33) and "short" 125I-D-Try-Gly-[(Nle28,31)CCK-26-33] probes that were cross-linkable through their amino terminus and a monofunctional probe with a photolabile group at its carboxyl terminus 125I-D-Tyr-Gly[(Nle28,31,pNO2-Phe33)CCK-26-33]. All probes specifically labeled a human gallbladder muscularis protein of Mr = 85,000 95,000, which was also independent of diagnosis. Labeling of this band was inhibited in a concentration-dependent manner by CCK-8 and by L-364,718. Thus, the CCK receptor present on the very common surgically removed human gallbladder is functionally and biochemically intact and is useful for further characterization. PMID- 2925057 TI - Amoxicillin-clavulanate potassium-associated cholestasis. AB - Amoxicillin-clavulanate potassium, a semisynthetic penicillin-beta-lactamase inhibitor combination drug, is a widely used oral antibiotic. Since the marketing of this drug in 1984, more than nine million prescriptions have been dispensed. Several cases of jaundice and hepatic dysfunction have been observed and reported to the Food and Drug Administration and the pharmaceutical company (Beecham Laboratories). A review of 18 of these cases revealed a predominantly cholestatic syndrome in 7 cases, a mixed hepatocellular-cholestatic picture in 6 cases, a hepatocellular pattern in 4, and in 1 case the injury could not be clearly defined. No fatalities were observed, and all cases had reversal of hepatic dysfunction upon cessation of the drug. Fever was present in 2 patients and eosinophilia in 6 of 10 patients tested, suggesting a hypersensitivity phenomenon contributing to hepatic dysfunction in some of the cases. A percutaneous liver biopsy had been performed in 7 of 18 patients and four of these were reviewed by the authors. Prominent centrizonal cholestasis was seen in all four biopsies. Additionally, 1 patient had periportal and another had midzonal cholestasis. Although infrequent, recognition of an often benign cholestatic syndrome associated with amoxicillin-clavulanate potassium will help avoid unnecessary, invasive, and expensive diagnostic studies and also ameliorate symptoms upon withdrawal of the drug. PMID- 2925058 TI - Determinants of bile secretion: effect of bile salt structure on bile flow and biliary cation secretion. AB - The effect of five bile salts, deoxycholate, chenodeoxycholate, cholate, ursodeoxycholate, and ursocholate, possessing (in decreasing order) different hydrophobicity, on bile flow and biliary secretion of total calcium, magnesium, sodium, and potassium was studied in 10 patients with T-tubes. Each subject was infused intraduodenally with one or two bile salts, given separately, to produce a selective enrichment of biliary bile salts with the infused bile salt. The choleresis induced per 1-mumol increase of bile salt output was greater during the secretion of 7 beta-hydroxylated bile salts, ursodeoxycholate (0.029 ml), and ursocholate (0.027 ml), followed in decreasing order by deoxycholate (0.023 ml), chenodeoxycholate (0.019 ml), and cholate (0.009 ml). Deoxycholate stimulated the greatest increase in cation secretion per unit increase in bile salt output, followed by chenodeoxycholate and cholate. The two 7 beta-hydroxylated bile salts induced greater cation secretion than did their 7 alpha-epimers. Whereas biliary concentration of divalent cations differed depending on the structure and concentration of the infused bile salt, the concentration of monovalent cations was constant for any species and concentration of infused bile salt. Relationships between bile salt and divalent cation concentration indicate that 1 mumol of secreted biliary deoxycholate, the most hydrophobic bile salt, associates with the greatest amount of calcium (0.046 mumol) and magnesium (0.022 mumol), followed by chenodeoxycholate (0.020 and 0.010 mumol, respectively) and cholate (0.012 and 0.008 mumol, respectively). The capacity of ursodeoxycholate and ursocholate to associate with calcium and magnesium seems to be less than that of their 7 alpha-epimers. These data suggest that of the common bile salts, the more hydrophobic bile salts stimulate bile flow and cation secretion better than the more hydrophilic bile salts, whereas ursodeoxycholate and ursocholate are more effective than their more hydrophobic 7 alpha-epimers. Whereas different bile salts seem to influence the secretion of sodium and potassium mainly by virtue of their choleretic properties, the effect of bile salt structure on biliary secretion of calcium and magnesium suggests the presence of a secretory link that might be consistent with cation-bile salt binding. PMID- 2925059 TI - Rat pancreatic nuclear thyroid hormone receptor: characterization and postnatal development. AB - To document the presence of 3,5,3'-triiodothyronine nuclear receptor in the rat pancreas, the solubilized pancreatic nuclear fraction was characterized for its binding to 3,5,3'-L-triiodothyronine. Binding was found to be reversible, saturable, and specific. Scatchard analysis revealed a single class of 3,5,3'-L triiodothyronine receptors in the pancreata of adult rats. The dissociation constant was 0.29 +/- 0.02 x 10(-9) M, and maximal binding capacity was 242 +/- 10 fmol of T3 bound per milligram of nonhistone protein at 30 degrees C (n = 20). Both parameters are comparable with those of adult rat liver nuclei. The degree of receptor occupancy was 30%-40% of the total sites in the adult rat pancreas. Developmentally, 3,5,3'-L-triiodothyronine binding was not detectable at birth and very low in pups less than 5 days old. It reached a peak at the third to fourth weeks. The degree of receptor occupancy changed with development from a low (19.2% +/- 2.0%) in 5-10-day-old pups to a high (50.5% +/- 3.0%) in 11-20-day old pups, then returned to a moderate level (36.9% +/- 3.0%). The dissociation constants remained unchanged at various postnatal ages. Our data suggest that the rat pancreas is a target tissue for thyroid hormone and that thyroxine plays a role in pancreatic development. PMID- 2925060 TI - Mortality factors associated with chronic pancreatitis. Unidimensional and multidimensional analysis of a medical-surgical series of 240 patients. AB - The purpose of the study was to determine (a) the frequency and cause of mortality in patients with chronic pancreatitis; (b) the cumulative survival rates corrected by comparison of patients with a matched French population; and (c) the factors associated with mortality by a unidimensional and multidimensional analysis. The study population consisted of 240 patients (men = 208, women = 32; alcoholic = 210, nonalcoholic = 30) followed for a mean time of 8.7 yr. The status of the patients (dead or alive) was recorded in February 1987. Mean age at onset of chronic pancreatitis was 41.5 yr. Fifty-seven patients died. Mean age at time of death was 52.3 yr. "Overmortality" after 20 yr of course was 35.8% in comparison with a matched French population (p less than 0.0001). Chronic pancreatitis was the direct cause of death for only 19.3% of patients. The main causes of death have been alcoholic hepatopathy (n = 10), cancer (n = 9), postoperative mortality (n = 8). Unidimensional analysis of mortality rates showed that male sex (p less than 0.03), surgery (p less than 0.007), hepatopathy (p less than 0.01), diabetes mellitus (p less than 0.02), and absence of attack of acute pancreatitis (p less than 0.02) were associated with mortality. Multidimensional analysis showed that the following variables were linked with mortality: in a first model including the totality of the study population: surgery (p less than 0.006), hepatopathy (p less than 0.008), no attack of acute pancreatitis (p less than 0.03), male sex (p less than 0.03); in a second model excluding cirrhosis: surgery (p less than 0.001), male sex (p less than 0.06), diabetes mellitus (p less than 0.09). Nevertheless, surgery did not seem to interfere with long-term mortality. The lower mortality of patients with attacks of acute pancreatitis suggests a favorable influence for alcohol abstinence. PMID- 2925061 TI - Effect of pancreatic juice diversion on secretin release in rats. AB - We investigated a possible role of secretin in the mechanism of exocrine pancreatic secretion after exclusion of pancreatic juice from the intestine in anesthetized rats. Diversion of pancreatic juice from the duodenum resulted in a significant increase in plasma secretin concentration from 0.76 +/- 0.39 pM at 0 time to 3.09 +/- 0.30 pM at 4 h after diversion. This increase in secretin coincided with a steady but significant increase in pancreatic secretion of volume and bicarbonate. Intraduodenal administration of fresh pancreatic juice completely reversed the diversion-induced increases in both plasma secretin and pancreatic secretion. Intravenous injection of a rabbit-antisecretin serum blocked the increase of pancreatic secretion during diversion of pancreatic juice from the duodenum. Thus, we conclude that endogenous secretin is involved in a hormonal mechanism regulating increased pancreatic exocrine secretion in pancreatic juice-diverted rats. PMID- 2925062 TI - Endoscopic biliary therapy using the combined percutaneous and endoscopic technique. AB - Between September 1985 and December 1987, 74 patients underwent attempted endoscopic biliary therapy using a combined percutaneous transhepatic and endoscopic transpapillary approach (combined procedure). All patients had had failed endoscopy-alone procedures and had contraindications to surgery. The indication was palliation of malignant biliary obstruction in 66 cases (41 common bile duct, 25 hilar), assistance with sphincterotomy for the removal of common bile duct stones in 6 cases, and management of benign biliary stenosis in 2 cases. The initial procedure was percutaneous transhepatic access to the biliary tree, which was successful in all but 1 case (99%). The bile duct was drained externally for an average of 3.4 days before the combined procedure. One patient died during this period from hemorrhage associated with liver puncture. Combined procedure was performed in 72 cases and was successful in 60 [53 malignant stricture (53/66 = 80%), five common duct stone (5/6 = 83%), two benign stricture (2/2 = 100%)]. Procedure-related morbidity and mortality, respectively, were 12.5% and 0% for benign disease and 36% and 3% for malignant disease. The total (initial endoscopy included) morbidity and 30-day mortality were 33% and 0%, respectively, for benign disease and 62% and 27% for malignant disease. Subsequently, stent change has been required on 16 occasions, with endoscopy-only successful in 13 (81%) and repeat combined procedure being required in three (19%). The combined procedure improves the ability of endoscopy to offer nonsurgical therapy to poor risk patients with both malignant and benign biliary disease but is associated with significant morbidity and disease-related mortality. PMID- 2925063 TI - Circadian variation in renal sodium and potassium handling in cirrhosis. The role of aldosterone, cortisol, sympathoadrenergic tone, and intratubular factors. AB - Renal sodium and potassium handling, plasma aldosterone and cortisol concentrations, and urine free norepinephrine excretion were determined every 4 h for 24 h in 15 cirrhotics (7 without ascites, group 1; 8 with ascites, group 2) and 7 healthy controls during controlled salt intake and recumbency. Renal sodium excretion was significantly reduced in group 2, whereas it exceeded threefold the salt intake in group 1. Its circadian rhythm was disrupted in both groups of patients. Significant inverse correlations with plasma aldosterone were found erratically in controls, never in group 1, and at every 4-h interval in group 2. In the latter, the indexes of tubular activity and effectiveness of aldosterone were also significantly increased. Urine norepinephrine excretion was never related to sodium excretion in either controls or patients; in group 2 it was directly correlated with glomerular filtration rate in many instances. The cortisol-related circadian rhythm of kaliuresis was retained only in group 1. The 24-h renal potassium excretion of controls and patients was comparable, in spite of the striking hyperaldosteronism, and the more than doubled contribution of aldosterone to kaliuresis shown in group 2. The influence of aldosterone on potassium excretion was also witnessed by the direct correlation between these variables found in group 1 and, when kaliuresis was corrected by the distal sodium delivery, group 2. Renal sodium handling in cirrhosis is altered even before ascites formation and compensated patients can undergo "spontaneous natriuresis." Aldosterone is the main cause of sodium retention in nonazotemic ascitic patients, while sympathoadrenergic hyperactivity may contribute to preserve renal perfusion. The influence of aldosterone on kaliuresis is enhanced, but renal potassium wasting in patients with ascites and hyperaldosteronism is prevented by reduced distal tubular availability of sodium. PMID- 2925064 TI - Fibrin ring granulomas and allopurinol. AB - To test the hypothesis that allopurinol-associated granulomatous hepatitis may present itself with fibrin-ring granulomas, we requested details of such cases, as reported to the World Health Organization, from 13 national adverse reaction monitoring centers, and as reported in the literature. Details and histology of 6 cases were obtained and reviewed. All consisted of acute hypersensitivity signs with fever, rash, arthralgia, or eosinophilia as hallmarks, starting within 6 wk of commencing treatment with allopurinol. In all cases there were either epithelioid granulomas or granulomalike lesions, but none of these contained fibrin rings. It is concluded that, if fibrin-ring granulomas are a manifestation of allopurinol-induced granulomatous hepatitis, this feature is probably uncommon. PMID- 2925065 TI - Iron overload complicating sideroblastic anemia--is the gene for hemochromatosis responsible? AB - Idiopathic hemochromatosis is a hereditary disease that is associated with human leucocytic antigens A3, B7, and B14. A genetic association between human leucocytic antigen-linked hemochromatosis and idiopathic refractory sideroblastic anemia has been suggested that may predispose some patients with idiopathic refractory sideroblastic anemia to develop gross iron overload. Study of the family of a patient with idiopathic refractory sideroblastic anemia and hemochromatosis revealed that 2 of 5 first-degree relatives had significant elevations of serum ferritin, and a shared human leucocytic antigen haplotype, supporting the concept that patients with idiopathic refractory sideroblastic anemia and significant iron overload have at least one allele for hemochromatosis. PMID- 2925066 TI - Breath hydrogen in bacterial overgrowth. PMID- 2925067 TI - Sorbitol clearance: shift from flow-limitation in controls to enzyme-flow dependence in cirrhosis. PMID- 2925068 TI - Campylobacter pylori and symptoms: is there a cause and effect relationship? PMID- 2925069 TI - Campylobacter pylori in acquired immunodeficiency syndrome. PMID- 2925070 TI - Zonal diversity or zonal heterogeneity in bile secretion. PMID- 2925071 TI - Gastric potential difference measurements influenced by changes in pH. PMID- 2925073 TI - Digestive Disease Week and the 90th annual meeting of the American Gastroenterological Association. May 13-19, 1989, Washington, D.C., Program and abstracts. PMID- 2925072 TI - Short-chain fatty acids stimulate active sodium and chloride absorption in vitro in the rat distal colon. AB - Studies were performed to determine the mechanism by which short-chain fatty acids increase colonic Na and Cl absorption by determining unidirectional 22Na and 36Cl fluxes across isolated stripped mucosa from the rat distal colon under voltage clamp conditions. Mucosal butyrate (25 mM, in the absence of bicarbonate) significantly enhanced both net Na and net Cl absorption by 7.0 +/- 1.3 and 6.9 +/- 1.0 microEq/h.cm2, respectively, without increasing the short-circuit current. Net Na and Cl absorption in butyrate-Ringer's solution and HCO3-Ringer's solution were identical. Butyrate stimulation of Na (and Cl) absorption was Cl dependent and prevented by 1 mM mucosal amiloride, an inhibitor of Na-H exchange, but was HCO3-independent and not inhibited by acetazolamide, a carbonic anhydrase inhibitor. In contrast, bicarbonate-stimulated Na (and Cl) absorption was also Cl dependent and amiloride-sensitive, but was significantly inhibited by acetazolamide. The effect of mucosal butyrate on net Na and Cl absorption was substantially greater than serosal butyrate, which in the presence of bicarbonate did not alter ion transport. The stimulation of Na and Cl absorption by mucosal butyrate was significantly greater than by propionate and acetate, whereas mucosal formate did not alter Na transport. The results of this study permit the following model: short-chain fatty acid stimulation of active Na and Cl absorption involves uptake of the nonionized form of butyrate and the coupling of Na-H and Cl-butyrate exchanges. PMID- 2925074 TI - Putative role of adenohypophysis in the osmoregulation of tilapia larvae (Oreochromis mossambicus; Teleostei): an ultrastructure study. AB - Ultrastructure of the secretory cells in the adenohypophysis of tilapia (Oreochromis mossambicus) larvae hatched in fresh water or sea water was compared. Adenohypophysis of newly hatched larvae of tilapia is a short columnar body attached to the ventral floor of the diencephalon. The adenohypophysis is at its early differentiation stage, i.e., various types of secretory cells are still undistinguishable. Only part of the cells in the putative rostral pars distalis look like typical endocrine cells, containing well-developed rough endoplasmic reticulum, Golgi apparatus, and numerous secretory granules. The average size of secretory granules in freshwater-hatched larvae is significantly larger than those in seawater-hatched larvae (12,936 +/- 2854 nm2, N = 11 vs 3375 +/- 810 nm2, N = 10), suggesting some role of adenohypophysis in the osmoregulation of the early developmental stage of teleosts. PMID- 2925075 TI - Production of methyl farnesoate by the mandibular organs of the mud crab, Scylla serrata: validation of a radiochemical assay. AB - Parameters for the validation of a radiochemical assay to monitor the biosynthesis and release of methyl farnesoate (MF) by the mandibular organs (MO) of the mud crab, Scylla serrata, have been defined. On the basis of HPLC analysis, MF appeared to be the exclusive radiolabeled product of release, using [3H-methyl]methionine as precursor. HPLC of isooctane extracts of medium in which MO had been maintained similarly revealed that MF was the exclusive 3H-product and indicates that the isooctane partition assay can be employed to monitor MF release. The time course of MF biosynthesis and release suggested that the endogenous L-methionine pool is large, because both cumulative release and rate of release increased over an 8-hr incubation but remained constant between 8 and 16 hr. Glandular content of MF did not appear to stabilize until 6-8 hr after the start of the incubation. Cumulative MF release, as a function of glandular content or biosynthesis, increased gradually with time, but even after 16 hr the majority of biosynthesized MF was retained within the MO rather than released. L Methionine concentration in the incubation medium influenced both MF biosynthesis and release, although the dose dependency was more apparent with biosynthesis. Although it was difficult to associate strictly a level of biosynthesis with L methionine concentration, low rates of MF biosynthesis were observed at concentrations of less than 25 microM. Because high levels of biosynthesis were observed consistently between 60 and 70 microM L-met, all subsequent incubations employed a concentration of 65 microM. MO of S. serrata show a striking asymmetry in MF biosynthesis and release which is not time dependent. Hence the comparison of right and left glands in assessing the effects of experimental treatments is precluded. PMID- 2925076 TI - Purification and characterization of Atlantic salmon prolactin. AB - Prolactin was isolated from the Atlantic salmon (Salmo salar) pituitary gland by extraction with acid acetone, gel filtration, ion exchange-chromatography, and reversed-phase high-performance liquid chromatography. The yield was 0.6 mg/g wet tissue. The hormone had a molecular weight of 23.5 kDa as determined by SDS polyacrylamide gel electrophoresis. Isoelectric focusing gave an isoelectric point of 9.2. The N-terminal sequence and the amino acid composition indicated extensive homology between Atlantic and Pacific salmon prolactin. Antiserum against Atlantic salmon prolactin cross-reacted with chum salmon prolactin, but not with human, rat, or sheep prolactin. PMID- 2925077 TI - Endocrines and osmoregulatory mechanisms in the Nile crocodile, Crocodylus niloticus. AB - The changes in body fluid economy and endocrine status associated with exposure of the Nile crocodile, Crocodylus niloticus, to hypertonic media have been related to the responses to altered renin-angiotensin system (RAS) activity observed in fresh water (FW) animals. Animals held in hypertonic media for 7 days showed a 18.2% body weight loss and raised plasma and urinary sodium, potassium, chloride, and osmotic concentrations. Within 6 hr of return to FW rapid imbibition had largely restored body weight and produced significant plasma dilution. Although plasma sodium, chloride, and osmotic concentrations remained higher than in FW controls, plasma levels of corticosterone, aldosterone, and arginine vasotocin were not significantly altered. Angiotensin I (AI) administration in FW crocodiles stimulated drinking and raised plasma aldosterone levels by comparison with animals given the converting enzyme inhibitor, Captopril, together with AI. The compensatory drinking behaviour exhibited by the Nile crocodile may thus involve the RAS. The RAS also appears to influence interrenal steroidogenesis and thus may afford an integrative role in crocodile fluid management as it does in homeotherms. PMID- 2925078 TI - Plasma catecholamine concentrations in rainbow trout (Salmo gairdneri) at rest and after anesthesia and surgery. AB - The effects of surgery and anesthesia on concentrations of plasma epinephrine (E), norepinephrine (NE), and dopamine (DA) were investigated in rainbow trout fitted with dorsal aorta cannulae. Baseline catecholamines (CA) concentrations, established in resting rainbow trout, were 1.55 +/- 0.90 pmol/ml (mean +/- SD) for E, 2.07 +/- 1.26 for NE, and 1.33 +/- 0.87 for DA. These values were based on the pooled analyses of five individual fish taken over seven different sampling periods. The E:NE ratio in resting fish was always less than 1.0. In a second experiment, fish were subjected to dorsal aorta cannulation and sequential blood samples were taken immediately after surgery, and 6, 24, and 48 hr later. Plasma E concentrations were 36 times greater than baseline values in the first sample; NE was 15 times greater and DA was 41 times greater. After surgery, plasma concentrations of all CAs fell rapidly but values were still higher than baseline 6 hr after surgery, then were near baseline at 24 and 48 hr after surgery. The E:NE ratio was about 3.0 immediately after surgery, dropped to 1.8 at 6 hr, and was about 1.0 at 24 and 48 hr. In a third experiment, plasma CAs were determined in a group of five animals anesthetized with tricaine methanesulfonate (100 mg/ml) to advanced anesthesia, and then allowed to recover in flowing well water over a 12-hr observation period. Plasma E and NE concentrations in the fish during early anesthesia (1.14 +/- 0.14 min) were not significantly different from preanesthesia values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2925079 TI - Seasonal changes in body weight, fat depots, and plasma levels of thyroxine and growth hormone in free-living great tits (Parus major) and willow tits (P. montanus). AB - Annual changes in body weight, fat depots, and plasma levels of thyroxine (T4) and growth hormone (GH) were studied in free-living great tits and willow tits. Birds were collected during six ecologically well-defined periods of the year. Special attention was given to the nonreproductive part of the year. T4 showed simple unimodal cycles in both species and both sexes, with high levels during the warmer part of the year, and low levels during the winter and spring periods. Although increasing levels were temporarily separated between the two species, they were in both cases correlated with the onset of gonadal regression and moult. Plasma levels of GH fluctuated in a much more complex pattern, and no obvious and consistent correlation to any extrinsic or intrinsic factor was found. Body weights and fat depots both showed seasonal variations that varied slightly between the two species. Values, with the exception for breeding females, were generally the highest during the autumn, winter, and spring periods. PMID- 2925080 TI - Purification of maturational gonadotropin from Atlantic croaker (Micropogonias undulatus) and development of a homologous radioimmunoassay. AB - The isolation of a maturational gonadotropin from pituitaries of Atlantic croaker (Micropogonias undulatus), a marine teleost belonging to the order perciformes, is described. A radioimmunoassay has been developed for the measurement of this hormone in blood samples and validation of the assay is presented. The hormone measured is an acidic isoform of GTH and can be detected in the plasma at concentrations from 25 to 0.05 ng/ml. At least one other gonadotropic fraction was detected during the purification. The acidic form of GTH is released from croaker pituitaries after stimulation with luteinizing hormone-releasing hormone analog (LHRHa), both in vivo and in vitro. The GTH is steroidogenic, is active in an in vitro oocyte germinal-vesicle breakdown assay, and is elevated in the blood of fish undergoing LHRHa-induced ovulation. PMID- 2925081 TI - Properties of follicle-stimulating hormone receptors and changes during annual breeding cycle in the testis of short-tailed bandicoot rat, Nesokia indica. AB - Some properties and seasonal changes of follicle-stimulating hormone (FSH) receptors in the testis of short-tailed bandicoot rat, Nesokia indica, were studied. The binding of FSH was highly specific for mammalian FSHs and located primarily in the testis. The Scatchard plot analyses of the binding of FSH to the testicular preparations of N. indica showed straight lines similar to those of albino Wistar rats, suggesting the presence of a single class of FSH-binding sites. The mean dissociation constants (Kds) for FSH receptors of N. indica were 1.416 (0.964-2.667, 95% confidence interval) nM in December, 1986; 1.348 (0.885 2.849) nM in April, 1987; and 3.039 (1.678-16.127) nM in August to October, 1987. No significant differences were found among the three groups, but they were all significantly greater than those in Wistar rats. The FSH binding per unit weight of tissue during non-breeding phase (June, 1987) was lower than those during other phases (December, 1986; April and August-October, 1987). Calculated numbers of FSH-binding sites showed no statistically significant differences among the latter three phases. In June preparations the number of binding sites was not determined due to their extremely low binding capacity. PMID- 2925082 TI - Periovulatory female goldfish release three potential pheromones: 17 alpha,20 beta-dihydroxyprogesterone, 17 alpha,20 beta-dihydroxyprogesterone glucuronide, and 17 alpha-hydroxyprogesterone. AB - Our previous studies have shown that 17 alpha,20 beta-dihydroxy-4-pregnen-3-one (17,20 beta-P) produced by preovulatory female goldfish functions both as a hormone promoting oocyte final maturation and as a primer sex pheromone stimulating rapid reproductive endocrine responses in the male. In the present study, the amounts of free and glucuronated 17,20 beta-P as well as free 17 alpha hydroxyprogesterone (17P) released to the holding water by female goldfish throughout the periovulatory period were determined. Compared to nonovulating female goldfish, ovulating goldfish released very high levels of each of these steroids. This study confirmed that 17,20 beta-P is released to the water by ovulating fish in sufficient amounts to have pheromonal activity and indicated that 17P may also function as a pheromone. Although considerable quantities of 17,20 beta-P glucuronide were also released, its physiological actions are unknown. PMID- 2925083 TI - Induction of gonadotropin surge by steroid hormone implantation in ovariectomized and sexually regressed female goldfish. AB - Involvement of steroid hormones in the occurrence of the ovulatory gonadotropin (GtH) surge was studied in goldfish. Ovariectomized female goldfish were implanted with an empty Silastic capsule or a capsule containing testosterone or estradiol, and kept below 12 degrees for 3 months (Experiment 1). Some of the steroid implanted fish showed a GtH surge which was quite similar to the normal ovulatory GtH surge in response to a water temperature rise from 12 to 20 degrees, whereas no surge was observed in fish with empty capsules. When sexually regressed female goldfish were implanted with the capsules containing testosterone or estradiol and kept at 12 degrees for 6 weeks out of spawning season, the GtH surge was also observed in these fish after the water temperature rise to 20 degrees (Experiment 2). The GtH surge was observed in a larger number of testosterone-implanted fish than in the estradiol-treated fish in both experiments. These results strongly suggest that the high plasma level of testosterone observed before ovulation is an important physiological requisite for the occurrence of the ovulatory GtH surge in goldfish. PMID- 2925084 TI - Corticosteroid receptors in liver cytosol of the clawed toad, Xenopus laevis: influence of thyroid and ovarian hormones. AB - The glucocorticoid receptor capacity Ro and the dissociation constant Kd were determined in the liver of Xenopus laevis by Scatchard analysis. In 5-year-old female toads Ro was about three times higher than that in males (153.9, 54.3 fmol/mg protein) and Kd was similar in both sexes (4.0, 4.1 nM). Some of the animals used had abnormal enlarged thyroid glands, atrophic ovaries, or both defects in connection with different levels of Ro, but not of Kd, compared to those of normal animals. Females with ovarian atrophy showed significantly lower Ro values, in the same range as in normal males, and a high liver weight. In male and female toads with enlarged thyroid glands and in animals with both defects a significantly higher Ro occurred compared to that of the corresponding group without this abnormality. To study the influence of thyroid hormones on glucocorticoid receptors, young toads (2-3 years old) received injections of 4 phenyl-2-thiouracil, T3, or T4 on 7 consecutive days. Ro and Kd were determined on the following day. Doses of 50 and 500 ng T3 and of 500 and 5000 ng T4 per gram of body weight and day resulted in an increase of Ro up to 250% of the controls. Injections of T3 were more efficient in males than in females. The effect of thyroxine was about the same in both sexes. These observations suggest that thyroid and ovarian hormones exert an influence on glucocorticoid receptor capacity and may belong to the factors which regulate glucocorticoid receptors. PMID- 2925085 TI - A network of influences on adolescent drug involvement: neighborhood, school, peer, and family. AB - The interrelationship of neighborhood, school, peer, and family factors and adolescent drug involvement was investigated. Data were collected separately from 518 adolescents and their mothers when the children were between 9 and 18 years of age and again two years later. Neighborhood and school effects were not directly related to adolescent drug use. Neighborhood effects were mediated through the domains of school, peer, and family; school effects were mediated through the peer domain. Family and peer variables had a direct impact on adolescent drug involvement. Risk factors in the adolescents' peer environment can be ameliorated by protective factors in their school environment. Implications for the prevention of drug use are discussed. PMID- 2925087 TI - Update on eosinophils. PMID- 2925086 TI - Mastocytosis in infants and children: recognition of patterns of skin disease. AB - Mastocytosis is a disease characterized by an increase in the number of tissue mast cells and a concomitant increase in mast cell-derived mediators. To demonstrate the spectrum of skin disease in mastocytosis in the pediatric population, five children with mastocytosis and complaints of urticaria (4/5), bullae/vesicles (3/5), abdominal pain (3/5), flushing (2/5), headache (1/5), and bone pain (1/5) are reviewed. Confirmation of the diagnosis of cutaneous mastocytosis was obtained by histologic examination of a biopsy of lesional skin; however, mast cell numbers in lesional skin did not correlate with plasma histamine levels or the extent of cutaneous involvement. Mastocytosis is a diagnosis that must be recognized in the differential diagnosis of pediatric urticarial diseases. PMID- 2925088 TI - Dietary supplements--eating well. PMID- 2925089 TI - Respite service--under cover of the night. PMID- 2925091 TI - Quality assurance: getting better. PMID- 2925090 TI - Support system. Interview by Paul Mangan. PMID- 2925092 TI - A caring community? PMID- 2925093 TI - Concepts of rehabilitation. PMID- 2925094 TI - An idea whose time has come. PMID- 2925095 TI - Insight: Martha and Mary. PMID- 2925096 TI - Hip fracture. Breaking point. PMID- 2925098 TI - Safer drug therapy for the elderly: progress has started. PMID- 2925097 TI - Neurologic presentation of a non-neurologic disorder. AB - Two elderly patients presented with neurologic changes that effectively masked a common, life-threatening condition. PMID- 2925099 TI - Electrochemical characteristics of nitro-heterocyclic compounds of biological interest. II. Nitrosochloramphenicol. AB - The electrochemical characteristics of nitrosochloramphenicol have been studied in aqueous buffer systems (pH 7.1) using direct current (d.c.) and differential pulse polarography, cyclic voltammetry and coulometric techniques. Up to 4 charge transfer steps can be identified. The first reduction step is reversible both chemically and electrochemically, the charge-transfer product showing no tendency to undergo further reaction on the electrochemical time-scale. In contrast, the second reduction step is irreversible, with the product undergoing a fast following reaction to yield a redox-active species which was detected by cyclic voltammetry. From the data and by comparison with related systems, two reduction mechanisms are possible and are discussed. PMID- 2925100 TI - Electrochemical characteristics of nitro-heterocyclic compounds of biological interest. III. Nitroso derivative formation. AB - Upon electrolytic reduction of a range of nitro-aromatic complexes (including imidazoles, benzenoids, furans and pyrazoles) an associated oxidation-reduction process is observed at more positive potentials with respect to nitro group reduction when using repeat scan cyclic voltammetry. This new couple has been identified as the reversible first reduction of the nitroso derivative for chloramphenicol, by the addition of a genuine sample of nitrosochloramphenicol to the electrochemical cell. We have failed to observe formation of the new redox active species for five 5-nitroimidazoles examined. Possible reaction schemes for nitroso formation under electrolytic reduction conditions and the importance of the nitroso redox couple with respect to the cytotoxic action of the parent drug are discussed. The applicability of nitrosochloramphenicol as a model for the behaviour of nitro-heterocycles in general is shown. PMID- 2925101 TI - The control of iron-induced oxidative damage in isolated rat-liver mitochondria by respiration state and ascorbate. AB - The reaction of iron (II) with H2O2 is believed to generate highly reactive species (e.g. .OH) capable of initiating biological damage. This study investigates the possibility that the severity of oxidative damage induced by iron in hepatic mitochondria is determined by the level of mitochondrial-H2O2 generation, which is believed to be particularly prominent in state-4 respiration. Iron-induced damage is found to be greater in state-4 than in state 3 respiration. Experiments using uncoupling agents and Ca++ to mimic state-3 conditions indicate that this effect reflects differences in the steady-state oxidation-level of the electron carriers of the respiratory chain (and hence the level of H2O2-generation), rather than changes in redox potential or transportation of the metal-ion. Evidence is also presented for a mechanism in which Fe(II) and H2O2 react inside the mitochondrial matrix. Ascorbate (vitamin C) is shown to be pro-oxidant in this system, except when present at very high concentration when it becomes antioxidant in nature. PMID- 2925102 TI - [Choice of the size and shape of a mitral valve prosthesis]. AB - The authors discuss the results of mitral valve replacement in 438 patients with intraoperative selection of the prosthesis and in 77 patients with preoperative selection by means of an original method based on two-dimensional echocardiography. The intraoperative selection proved to be insufficiently effective: in the postoperative periods 13.9 +/- 2.7% of patients had marked signs of lack of correspondence of the prostheses to the size and structure of the left ventricle, which was verified at autopsy or by the findings of intravital catheterization of the heart with ventriculograph. The method of preoperative selection of the prosthesis, which was suggested by the authors, is more effective. It allows implantation of an inadequate prosthesis to be absolutely avoided. The method showed implantation of a ball prosthesis to be contraindicated for 33.7 +/- 5.4% of patients with mitral and mitral-aortic valvular diseases. PMID- 2925103 TI - [Long-term results of the surgical treatment of aneurysm of the ascending aorta in combination with aortic valve insufficiency]. AB - Four of 28 patients who were operated on died in late-term periods, four from advancing cardiac failure and one died 5 years after an operation from cardiac tamponade. In the group of four patients one underwent Cabrol's operation, three were operated on by the Bentall-De Bono method. The condition of 25 patients considerably improved and they were related to the II and I functional classes. The result was poor in three patients due to initial severity of the process in one, dilatation of the arch of the aorta in another, the presence of a fistula in the distal anastomosis in the third. One patient treated by Cabrol's operation and another who was operated on by the Bentall-De Bono method had pseudoaneurysms in the orifices of the coronary arteries. Despite some complications which occurred in the late postoperative periods, the Cabrol and Bentall-De Bono operations are the most radical means today for surgical treatment of aneurysms of the ascending aorta. PMID- 2925104 TI - [Quantitative assessment of the aorta and pulmonary artery in normal subjects (comparison of data from echocardiometric and morphometric studies)]. AB - Fifteen children whose age ranged from 5 to 15 years were examined by the method of two-dimensional echocardiography to calculate the quantitative characteristics of a normal aorta and pulmonary artery. To determine the character of correlation of these data with the findings of morphometric examination of the heart, the results were compared with the morphometric data in 21 children of the same age. The study showed that echocardiography makes it possible to calculate the size of the semilunar valves quite precisely. In standardization of the echocardiometric examination the parameters correlate well with the findings of morphometry, while the differences between them do not exceed 6-7%. It proved that the quantitative characteristics of the aorta and pulmonary artery were determined by the body surface area, but due to the non-linearity of their dependence on it, they change according to strictly specific patterns. PMID- 2925105 TI - [Prognosis of the results of closed mitral commissurotomy based on data of preoperative M-echocardiographic assessment of the state of the mitral valve]. AB - A favourable result of closed mitral commissurotomy was prognosticated in patients with "pure" mitral stenosis, with no radiological signs of valve calcinosis, according to the findings of M-echocardiography. The first stage of prognostication is selection of patients with structural affection of the cusps rated no higher than 4 marks and of the chordae--no more than 2 marks. The second stage is analysis of the functional signs: amplitude of diastolic movement of the anterior cusp of the mitral valve, the rate of its opening and closure, and relative value of septal-cuspal separation. The third stage--determination of the type of prognosis (authentic, doubtful, negative) according to the gradation of the obtained values of the functional echocardiographic signs. PMID- 2925106 TI - [Sclerosing endoscopic therapy of expiratory stenosis of the trachea and the principal bronchi]. AB - The article deals with experimental substantiation and clinical application of sclerosing endoscopic treatment of expiratory stenosis of the trachea and main bronchi. It was established that it ensures a stable therapeutic effect in primary expiratory stenosis. The method may be one of the components of complex treatment of some patients with secondary forms of the stenosis. PMID- 2925107 TI - [Blood circulation in the lungs during prolonged occlusion of the principal branches of the pulmonary artery and following restoration of their patency in experimental conditions]. AB - The results of experiments on 36 dogs showed that in a lung with a ligated pulmonary artery the vascular network is maintained and the circulation of blood occurs through the bronchial arteries and their anastomoses with the pulmonary artery. The blood flow and total vascular bed increase in a functioning lung and the pulmo-arterial resistance diminishes. Desobliteration of the pulmonary artery leads to restoration of the main blood flow in it and the gas-exchange function of the lung which had been operated on, and to normalization of hemodynamics in the contralateral functioning lung. PMID- 2925108 TI - [Surgical treatment of total anomalous drainage of the pulmonary veins]. AB - The article discusses the results of radical correction of total anomalous drainage of the pulmonary veins in 5 patients; 4 had the supracardial and 1 patient--the cardial type of the anomaly with drainage of all pulmonary veins into the coronary sinus. Some details of the surgical intervention are described; some findings of the examination in late postoperative periods (2.0 +/- 1.15 years, on the average) are discussed. PMID- 2925109 TI - [Evaluation of the blood supply to the bronchial stump following resection of the lungs using a mechanical suture in the diagnosis and treatment of pulmonary hemorrhage]. AB - The authors analysed angiograms of 34 patients who had been operated on the lungs with the use of mechanical suturing instruments to determine the effect of the mechanical suture (MS) of the bronchial stump on the development of hemoptysis and pulmonary hemorrhage. They studied the possibility of applying transcatheter endovascular occlusion (TEO) of the bronchial arteries (BA) in the management of hemoptysis of this etiology. In 70% of patients hyperplasia of the BA developed in the MS region in the late postoperative period; which was the source of pulmonary hemorrhage in 75% of cases. Among the patients, 19 were subjected to BA TEO for pulmonary hemorrhage. In 13 cases the bronchial stump with MS was the source of hemorrhage. Hemoptysis is a late complication of lung resection with the use of MS. Preference should be given to BA TEO in the management of this complication. PMID- 2925110 TI - [Central hemodynamics in the early postoperative period following lobectomy and pneumonectomy]. AB - Comparative study of the peculiarities of central hemodynamics before operation and in the early postoperative periods was conducted in 48 patients with lung carcinoma managed by lobe- and pneumonectomy. Lung carcinoma of central localization is characterized by increased contractility of the right-ventricular myocardium. In the postoperative period after pneumonectomy the right ventricle experiences an increased load requiring considerable mobilization of the cardiovascular system. Lobectomy is attended by more marked and less stable changes in the function of the cardiovascular system in the early postoperative period. PMID- 2925111 TI - [Plasmapheresis in the combination therapy of patients with pyogenic destructive diseases of the lungs and pleura]. AB - Plasmapheresis is an effective method for controlling the resorption factor in patients with pyogenic destructive diseases of the lungs and pleura. It facilitates rapid normalization of the parameters of the patients' clinical condition and the radiological picture, and reduces endogenous intoxication. Protein-volemic disorders are more manifest in patients with a fatal outcome, which increase with the gradual progression of the disease and must be corrected before performing plasmapheresis. PMID- 2925112 TI - [Diagnosis and treatment of peptic strictures of the esophagus]. AB - In the period between 1963 and 1986 there were 189 patients with peptic stricture of the esophagus under observation. The peptic stricture was primary in 149 and secondary in 40 patients. Complex diagnosis of the disease allowed an adequate therapeutic tactics to be chosen. The management of peptic strictures should be started in all cases with nonoperative measures including bougienage. Such treatment produced a stable effect in 47% of cases. Various operative interventions were carried out in 53% of patients. Fundoplication in combination with selective proximal vagotomy was the most sparing and effective operation in primary peptic stricture; a secondary stricture had to be treated most frequently by resection of the esophagus, which was completed by valvular esophagogastroanastomosis. The late results proved best in primary peptic stricture. PMID- 2925113 TI - [Clinico-experimental evaluation of methods of aortic annuloplasty during aortic valve prosthesis]. AB - Various methods of aortoannuloplasty in replacement of the aortic valve in patients with a narrow root of the aorta were evaluated experimentally. It is shown that the simplest method for dilatation of the root of the aorta is that suggested by Nicks, which allows the effective diameter of the root to be increased to 4.5 mm. The Rastan-Konno operation is most radical, the diameter of the fibrous ring is increased by 13.5 mm on the average. The method, however, is technically difficult and injurious. A working classification of the severity of a narrow root of the aorta is suggested and operative methods for each case are recommended. PMID- 2925114 TI - [A case of successful closure of a rupture of the interventricular septum in acute myocardial infarct]. PMID- 2925115 TI - [Emergency replacement of a biological prosthesis by a mechanical prosthesis following clinical death]. PMID- 2925116 TI - [Cabrol's new anastomosis in repeated prostheses of the ascending aorta and the aortic valve]. PMID- 2925117 TI - [A double mitral valve in combination with primary and secondary defects of the interatrial septum]. PMID- 2925118 TI - [Ligation of patent ductus arteriosus, removal of an aneurysm of a segmental artery and resection of the left lung]. PMID- 2925119 TI - [A combined rupture of the interventricular septum and the tricuspid valve in closed chest injury]. PMID- 2925120 TI - [Arthrodesis of the metacarpophalangeal joint of the thumb. Indications, technic, arthrodesis angle and functional effect]. AB - The metacarpophalangeal joint of the thumb has less range of motion than any other digital joint. Its stability is more important than its mobility. Thus, arthrodesis of this joint causes relatively little loss of function, provided only that the joint is fused in the correct position. The authors reviewed all MP joint fusions of the thumb which were done at their hospital between 1974 and 1985. They examined individually forty-one of the fifty patients and studied the indications, surgical techniques and difficulties, and the complications. Furthermore, they measured all angles of fusion and concluded that the optimal position is fifteen degrees of flexion and ten degrees of pronation. The use of tension band wiring facilitates the achievement and maintenance of the desired position. The stability of the fusion permits exercise immediately after the operation; this helps to avoid a tenodesis of the long extensor tendon of the thumb. PMID- 2925121 TI - [Multi-sided free transplants for closure of multifocal tissue defects]. AB - Recently microsurgical tissue transfer--especially to the distal lower leg--for coverage of big soft tissue defects has been found to yield better results than conservative methods. However, there is still a problem providing coverage for multiple defects with only one tissue transfer. One solution is to employ multiple transplants with only one nourishing pedicle. Six patients have been treated successfully with such transplants. The operative procedure and the postoperative results are presented with a case report. PMID- 2925122 TI - [A sub-pectoral gliding flap for covering the lateral triangle of the neck]. AB - The subpectoral connective tissue can be isolated and transferred on a vascular pedicle (pectoral branch of the thoracoacromial artery). It was demonstrated by cadaver dissection that this flap covers the fossa supraclavicularis and can reach the mandibular angle and in some cases the cheek. This flap was used clinically to envelope the fibrotic brachial plexus after neurolysis, in the treatment of a pain syndrome in which several simple neurolyses had previously failed. PMID- 2925123 TI - [Continuous axillary catheter plexus anesthesia--a method of postoperative analgesia and sympathetic nerve block following hand surgery]. AB - During a period of one year (March 1985 to March 1986) 52 axillary brachial plexus catheters were left in place for two to twelve days. The main indications were postoperative analgesia and sympatholysis after microvascular surgery of the hand. With the continuous infusion of 0.25% or 0.375% bupivacaine, 6-8 ml/h a sufficient effect was seen. There was no evidence of accumulation of the administered drug after a prolonged period of infusion. A steady state of serum levels built up in the range between 0.5 to 1.5 micrograms/ml. There were no toxic side effects by the local anaesthetic agent. In one case an infection of the axillary region developed, which disappeared after removal of the catheter without any consequences. In summary the continuous axillary brachial plexus block is an acceptable method for intra and postoperative analgesia and sympatholysis in microvascular surgery of the hand. PMID- 2925124 TI - [Scanning electron microscopy studies following two-stage tendon and tendon sheath reconstruction in experimental flexor tendon injuries]. AB - This study involves the initial injury of a flexor tendon in chickens toes, followed by a two-step reconstruction of the tendon and its sheath. At first the damaged scarred tendon sheath region was replaced by a transplanted vein or fascia. Tendon restoration was done in the second step with a free tendon transplantation. The restored tendon sheath was then studied in sections under EM. It was observed that the surface of the reconstructed sheath was very similar to that of an intact sheath; the inner surface of the fascia being smoother than the vein. Likewise, the surface and inner structure of the transplanted tendon was proved to resemble an intact tendon. On the basis of the results of this investigation, it is believed that this procedure may be successfully applied to the reconstruction of human flexor tendon injuries in the future. PMID- 2925125 TI - [Correction of the deformed hand in Parkinson disease]. AB - The typical hand deformity of Parkinsonism consists of metacarpophalangeal joint flexion and interphalangeal joint extension. An unusual case of a claw hand deformity in a patient with Parkinson's disease is described with hyperextension in the metacarpophalangeal joints and flexion in the interphalangeal joints. The operative technique to improve the marked limitation in hand function is described. PMID- 2925126 TI - [Comments on vascular pedicled nerve transplantation in the area of the upper extremity]. AB - This article describes the vascular anatomy of several nerves of the upper extremity with a view of their potential use as pedicled, vascularized nerve grafts. PMID- 2925127 TI - [Initial results following implantation of silastic wrist joint prostheses in patients with chronic polyarthritis with additional use of titanium grommets]. AB - Implantation of titanium grommets should protect the flexible implant from the sharp bone edges and avoid fracture of the implant. In case of bone cysts and thin corticalis they should provide further support against countersinking. Swanson et al. (1982) reported bone remodeling phenomena around the grommets and the implant. Eight patients suffering rheumatoid arthritis have been reviewed at an average of 18 months (12 to 24 months) following operation with the flexible implant and additional grommets. The following results were observed: 1. No fractured implants were noted in any patient. 2. In two cases resorption was noted around the proximal grommet. 3. In no case was new bone formation noted. 4. In one case the flexible implant and the grommets became countersunk into bone. PMID- 2925128 TI - [The fate of the polytraumatized patient with a "minor injury" of the hand]. AB - In the case of a multiply injured patient an inconspicuous injury in the finger led to a poorly functioning hand despite rehabilitation. PMID- 2925129 TI - Death and disaster. PMID- 2925130 TI - Morphological findings in fatal drug addiction. An investigation of injection marks, endocrine organs and kidneys. AB - Tissue sections from injection marks from 30 drug addicts and sections from endocrine organs and kidneys from an additional 33 addicts were studied together with endocrine organs and kidneys from 20 'normal' persons. All 83 persons were submitted for medico-legal autopsy at the Institute of Forensic Medicine in Copenhagen. In fresh injection marks haemorrhage in dermis and subcutis was present histologically in all cases. Acute inflammation was present in 38% and acute inflammation together with chronic changes in 41%. Fibrotic thickening of vein wall was seen in 14% and thrombosis in 10%. Birefringent foreign material occurred in 35%. In old injection marks and scars chronic inflammatory changes were observed in 93%, fibrotic thickening of vein wall in 20% and thrombosis in 10% of the cases. Birefringent material occurred in 17%. By comparison of changes in injection marks with the size and histological changes in the corresponding axillary lymph nodes, there was a tendency to a relation between chronic inflammatory changes in old injection marks/scars and enlargement of the lymph nodes in question, but no correlation to the histological degree of immunoactivity. Regarding alterations in the endocrine organs and the kidneys no important differences were demonstrated between drug addicts and 'normal' persons. PMID- 2925131 TI - Barbiturate analysis in tissue by enzymic digestion and high-performance liquid chromatography. AB - The relative efficiencies of four enzymic digestion procedures and two conventional methods in releasing barbiturates from spiked liver tissue have been compared. The recoveries of these acidic drugs obtained by using papain and neutrase (neutral proteinase from Bacillus subtilis) digestion methods reported now for the first time are higher than those by other enzymatic and conventional methods. These observations are similar to our earlier data on the applicability of these two enzymes to the release of some basic drugs from tissue. Papain digestion gives the maximum recovery of drugs as monitored by HPLC and is the method of choice. The enzymic digestion procedures are relatively simple, inexpensive and yield reproducible results. Analytical procedures for use in routine forensic toxicological analysis are presented. PMID- 2925132 TI - Study on the effects of heat on blood and on the post-mortem estimation of carboxyhaemoglobin and methaemoglobin. AB - Blood samples of different carboxyhaemoglobin (CoHb) content (0%, 50%, 100%) were analysed, after short exposure to heat, for determination of the change of CoHb and methaemoglobin (MetHb) during the succeeding 14 days. Untreated blood showed an initial increase of MetHb after heating followed by a decrease during this period. There was no formation of CoHb in the untreated blood. When CoHb was already present in the blood the amount of MetHb was smaller in amount and was formed at a slower rate. In these samples the concentration of CoHb slowly decreased. PMID- 2925133 TI - Diagnostic value of the placenta in medico-legal practice. AB - In three suspected cases of infanticide, histological examinations of the placentas were effective in clarifying the circumstances. We have estimated the 5th month of pregnancy from pieces of the placenta in one case and diagnosed the causes of perinatal abnormalities in two cases, those being acute chorioamnionitis and possible premature separation of normally implanted placenta. PMID- 2925134 TI - [Materials properties of zinc phosphate cements after delayed setting on refrigerated slabs]. AB - Two of the zinc phosphate cements commonly used in orthodontics were mixed, with special attention being paid to the longest possible working time, and examined by scientific methods. The results showed that mixing should generally be carried out on frozen slabs (-18 degrees C to -24 degrees C) and for not longer than 5 min. If a maximum compressive strength is required, mixing should be done at refrigerator temperature (+4 degrees C to +8 degrees C) for no more than 1.5 min by accepting a shorter working time. Neither cement shows any notable physicochemical differences, as regards the material. PMID- 2925135 TI - [The effects of functional diagnostic measures on orthodontic planning and therapy]. AB - Patients with significant functional disorders were pretreated with a relaxation splint before planning orthodontic treatment. The orthodontic diagnostic procedures were completed with extensive clinical and instrumental examinations of function (articular diagnosis and axiography) before and after the pretreatment. The studies show that the pretreatment for patients with TMJ disorders is necessary for the differential diagnosis. Furthermore, this may become necessary in order to determine the individual acceptable therapeutic mandibular position. In most cases, the axiography was found to be of minor relevance for the orthodontic therapeutic plan. If the functional improvement is intended to have a stable and causal basis, then an extensive clinical and instrumental functional examination (for the determination of a reproducible mandibular reference position) is crucial at least in TMJ-disordered patients for planning and carrying out orthodontic treatment. PMID- 2925136 TI - [The effect of passive plates on the arrangement of the alveolar arch segments in unilateral total cheilognathopalatoschisis]. AB - Maxillary alveolar arch morphology was studied from birth to palate repair at the age of 19 months in 24 children with complete unilateral cleft lip and palate (UCLP) treated with passive orthopaedic plates (treated children). 18 children with the same defect, who received no orthopaedic treatment, served as controls. The surgical procedures and the age at lip and palate repair were similar. Maxillary alveolar arch morphology was described by 15 linear and five angular measurements. No significant difference was found in total alveolar crest length neither between the cleft and the non-cleft maxillae nor between the treated children and the controls. Anterior alveolar arch width was significantly larger in the treated children at lip repair and at palate repair. Posterior alveolar arch width was significantly larger in the treated children at lip repair only. There was no significant difference in alveolar cleft width between the treated children and the controls at lip or at palate repair. Palatal cleft width decreased significantly in the treated children only. Medial rotation of both the cleft and the non-cleft maxillae was observed in both groups. The main difference was the absence of arch collapse in the treated children. At palate repair the relationship between the two maxillae was more favourable in the treated children for the development of the occlusion. The occlusion of the mixed dentition will be subject of a subsequent follow-up. PMID- 2925137 TI - [The effects of premature deciduous molar loss on the succeeding premolars]. AB - By means of panoramic radiographs of 76 patients we investigated the development and eruption of lower premolars following premature loss of their deciduous predecessor. Following extraction of deciduous molars the mineralization of the bicuspids was accelerated. The eruption of the respective bicuspids took place earlier than expected. During eruption root length was shorter than usual for that stage of development. Although the bicuspids reached occlusion earlier than normal, root mineralization continued to normal length. PMID- 2925138 TI - [Reproducibility of rhinomanometric measurements of nose breathing resistance and of x-ray cephalometric recordings of the natural head position in children]. AB - The reproducibility of rhinomanometric recordings of nasal resistance to breathing and of cephalometric recordings of natural head position was studied in 30 children aged seven to 13 years. Posterior rhinomanometry, with and without decongestion of the nasal mucosa, was performed on two occasions. Rhinomanometric registration was possible in 92% of the children but the recorded values for air flow showed a considerable intraindividual variation. The natural standing position of the head and of the cervical spine as well as the relation between the head and the cervical spine was recorded in profile by X-ray cephalometry on two occasions. During the recording, the subject was looking at his face in a mirror. Systematic differences between the duplicate determinations and an accidental error of 4 degrees in the determination of the position of the head and the cervical spine were found. In about 10% of the cases, the differences between the duplicate determinations were greater than 10 degrees. PMID- 2925140 TI - [Subarachnoid hemorrhage as a cause of acute headache]. PMID- 2925139 TI - [Do growth-promoting hormones have an effect on dentition development in dwarfism?]. AB - In children with nanism we differentiate between hypophyseal ateleiosis, constitutional retarded development with slow bone maturation and familiar ateleiosis. The somatotrope hormone is responsible for growth. With this hormone we can stimulate the growing process in hypophyseal ateleiosis and in constitutional retarded development. Human growth hormone accelerate growth and bone maturation in the same way, also anabolics stimulate growth, especially bone maturation. They also accelerate the development of the dentition, as shown by the example quoted. The best time for orthodontic treatment is during intensive growth periods the specific skeletal age taking into account. PMID- 2925141 TI - [Our senior citizens]. PMID- 2925142 TI - [Metabolism of high density lipoproteins. Studies in patients with compensated, postinfectious liver cirrhosis]. AB - The distribution of high density lipoprotein subclasses 2 and 3 in the plasma is considered to be regulated within the vessels. This view is refuted by the results of the present investigation, which show that the liver has a major and differentiated role in the metabolism of the high density lipoprotein subclasses. This supports the concept of a preferential role of HDL2 subclass in reverse cholesterol transport. PMID- 2925143 TI - [Gene therapy in the human. Recommendations of the European Medical Research Councils]. PMID- 2925144 TI - [AIDS. HIV antibodies detected in saliva]. PMID- 2925145 TI - [Promoting pneumologic basic diagnosis. Respiratory tract diseases are the cause of the majority of disability certificates--diagnosis with apparatus- possibilities for settlement]. PMID- 2925146 TI - [Pain and the origin of treatment. Continuing education course. 25 November 1988, Bad Nauheim]. PMID- 2925147 TI - [Long-term therapy using non-steroidal antirheumatics. Workshop "Osteoarthritis: new hints" presented at the 5th symposium of the European League Against Rheumatism (EULAR). 9 November 1988, Paris. Abstracts]. PMID- 2925148 TI - FNS begins only "refresher" program for nurse-midwives in USA. PMID- 2925149 TI - Hemoglobin as a direct inhibitor of cartilage growth in vitro. AB - Growth retardation is a feature of several diseases associated with chronic hemolysis (i.e., uremia and the hemoglobinopathies). Although the growth failure is undoubtedly multifactorial, circulating hemoglobin (Hb) may inhibit cartilage growth directly. We tested this hypothesis using the hypophysectomized rat costal cartilage sulfation bioassay and the embryonic chicken pelvic rudiment bioassay, both very sensitive to growth factors and growth inhibitors. In the rat bioassay, Hb produced a dose-dependent inhibition of both basal and normal rat serum (NRS) stimulated 35SO4 uptake. In the chick bioassay, NRS stimulated cartilage growth as expected, but Hb severely inhibited both basal and NRS-stimulated growth. However, after the cartilages were preincubated with Hb for 2 days, subsequent exposure to NRS allowed them to resume growth at the same rate as cartilage exposed to NRS for the entire 5 days. The growth inhibition could be accounted for by the heme contained in Hb. We conclude that Hb produces a dose-dependent and reversible inhibition of cartilage growth and may contribute to the growth retardation associated with chronic hemolytic conditions. PMID- 2925150 TI - Aluminium accumulates on inactive bone surfaces after parathyroidectomy in uremic rats. AB - In recent studies on bone biopsies of long-term hemodialyzed patients, parathyroidectomy (PTx) has been shown to represent a risk factor for subsequent accumulation of aluminium (Al) in the bone. Therefore, the influence of late PTx on Al metabolism in uremic rats previously given 11 mg Al intraperitoneally during a period of four weeks was studied. Al content was determined in the blood, liver, bone and feces 7 and 14 days after PTx. During PTx, each animal also received 2 intramuscular implants of partially demineralized bone matrix cylinders, which served as inactive bone surfaces. In PTx animals, the Al content in the liver, spleen and kidney progressively decreased, while its blood levels increased in spite of the fact that the treatment was stopped. Bone values remained unchanged but Al markedly accumulated on inactive mineralized surfaces of implanted cylinders. Significant amounts of Al in fecal masses could indicate its biliary excretion. The results were influenced neither by changes in 1,25 (OH)2D3 or serum calcium values, nor by different degrees of renal failure after PTx. It is suggested that accumulation of Al in the bone after PTx, as found in dialyzed patients, constitutes a passive event triggered by inactive bone tissue. PMID- 2925151 TI - Progression of diabetic retinopathy and changes in serum insulin-like growth factor I (IGF I) during continuous subcutaneous insulin infusion (CSII). AB - The rise in serum IGF I concentration during continuous subcutaneous insulin infusion (CSII) may be a contributory factor in the deterioration of diabetic retinopathy that sometimes occurs during this treatment but the relation of serum levels to the severity of retinopathy has not been previously studied. In twelve non-obese insulin dependent diabetics (age range: 22-41 yrs) with mean +/- SD duration of diabetes: 14.8 +/- 4.7 yrs, serum IGF I concentration, HbA1 and retinopathy score were estimated prospectively over twelve months following the institution of CSII therapy. After four months of treatment, eight patients showed deterioration of retinopathy by at least one level of severity. Serum IGF I concentration rose from a mean +/- SEM of 155 +/- 17.7 micrograms/l at entry to 199 +/- 23.1 micrograms/l at four months and by twelve months had returned to near initial values 163 +/- 17.4 micrograms/l. There was however, no significant correlation between retinopathy score and serum IGF I level by analysis of variance for the whole group, or in the group of diabetics whose retinopathy deteriorated. The rise in IGF I concentration over the first four months and subsequent decline in IGF I values over the next eight months was inversely related to HbA1 concentration (r = -0.58; P less than 0.05). One patient with early ischaemic retinopathy on entry, experienced a marked rise in serum IGF I corresponding to a rapid tightening of glycaemic control. At four months she developed florid proliferative changes requiring panretinal laser therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2925152 TI - Urinary dopamine, noradrenaline and adrenaline in type 2 diabetic patients with and without nephropathy. AB - We measured the urinary excretions of dopamine, noradrenaline and adrenaline, their conjugated metabolites, urinary excretion of sodium and creatinine clearance simultaneously in 21 patients with Type 2 (non-insulin-dependent) diabetes and 6 normal subjects. The mean (+/- SEM) value for urinary excretion of dopamine (52.4 +/- 8.8 micrograms/day) in diabetic patients with nephropathy (Group C, n = 12) was significantly lower (P less than 0.01) than in the normal subjects (Group A, 179.7 +/- 15.5 micrograms/day) and in diabetic patients without nephropathy (Group B, n = 9, 131.5 +/- 16.5 micrograms/day). The mean values for the urinary excretions of noradrenaline and adrenaline were also significantly lower (P less than 0.01) in Group C than in Groups A and B. In addition, the mean urinary excretion of conjugated metabolite of dopamine in Group C was significantly lower (P less than 0.05) than in Group A. There was a trend toward the observation that the mean 24-h urinary excretion of sodium in Group C (121.6 less than 12.9 mEq) was lower as compared with that in Group A (140.8 +/- 8.9 mEq) or B (150.7 +/- 17.9 mEq). A multiple regression analysis revealed that the 24-h urinary excretion of dopamine correlated significantly with creatinine clearance, systolic (P less than 0.01) and diastolic (P less than 0.05) blood pressures. The results indicate that synthesis or secretion of renal dopamine might decrease with a progression of diabetic nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2925153 TI - Ketoconazole and vitamin D metabolism in hyperparathyroidism. PMID- 2925154 TI - Gentamicin nephrotoxicity in extrahepatic cholestasis: modulation by dietary calcium. AB - The present study was designed to test the hypothesis that the presence of a specific hepatobiliary disease, namely common bile duct obstruction, in the absence of other risk factors will exacerbate gentamicin nephrotoxicity. Furthermore, since bile duct ligation decreases urinary calcium excretion, we studied the role of calcium supplementation in the prevention of gentamicin nephrotoxicity in this model. Male Sprague-Dawley rats were allocated to sham groups and common bile duct ligation groups. Gentamicin at 40 and 100 mg per kg per day for 5 days induced a more severe azotemia in common bile duct ligation animals than in sham controls. Furthermore, higher levels of renal gentamicin were found in common bile duct ligation rats than in sham rats early in the course of therapy, at its termination and during the recovery period. Pretreatment of common bile duct ligation animals with dietary calcium supplementation significantly attenuated gentamicin nephrotoxicity and the increased renal gentamicin accumulation, whereas initiation of calcium supplementation concurrent with gentamicin administration had no salutary effect. We conclude that experimental extrahepatic cholestasis in the rat, in the absence of any other factor, potentiates gentamicin nephrotoxicity. The effect is prevented by pretreatment with dietary calcium supplementation but is not modified by concurrent administration of a high-calcium diet. PMID- 2925155 TI - Vitamin E deficiency in primary biliary cirrhosis: gastrointestinal malabsorption, frequency and relationship to other lipid-soluble vitamins. AB - In contrast to deficiencies of vitamins A, D and K, little is known of the prevalence, clinical manifestations and mechanisms of vitamin E deficiency in adult patients with cholestasis. We measured serum vitamin E levels in 45 patients with primary biliary cirrhosis, 20 with primary sclerosing cholangitis, 9 with cryptogenic cirrhosis and 12 with alcoholic cirrhosis. To correct for the hyperlipidemia often found in patients with primary biliary cirrhosis and primary sclerosing cholangitis, total serum lipids were measured and vitamin E levels were expressed as the vitamin E/total serum lipid ratio. Serum vitamin A and D levels and prothrombin time were also determined. Six of 45 patients with primary biliary cirrhosis (13%) but none of the patients with sclerosing cholangitis, cryptogenic cirrhosis or alcoholic cirrhosis and subnormal vitamin E/total serum lipids ratios. Vitamin E deficiency was found in two of eight patients with asymptomatic primary biliary cirrhosis. There was no correlation between standard liver biochemical tests, fasting serum cholylglycine and vitamin E levels. Patients with primary biliary cirrhosis and primary sclerosing cholangitis had significantly lower vitamin E/total serum lipids ratios than patients with either cryptogenic or alcoholic cirrhosis. Twenty-three percent of patients with primary biliary cirrhosis were vitamin D deficient and 14% had low vitamin A levels. Two of the six patients with vitamin E deficiency were also deficient in vitamin D, only one was vitamin A deficient and none had prolonged prothrombin time. We also investigated the gastrointestinal absorption of vitamin E in nine patients with primary biliary cirrhosis and normal vitamin E levels as well as in six normal controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2925156 TI - Benign recurrent intrahepatic cholestasis: a long-term follow-up study of two patients. AB - Two brothers with benign recurrent intrahepatic cholestasis were studied over a period of 6 years. During this period, 11 episodes of cholestasis were observed, with a mean duration of 2.6 months (range: 2 weeks to 6 months). Once, both brothers developed cholestasis simultaneously. There was a prevalence for episodes of cholestasis in wintertime. The postprandial rise in serum sulfated glycolithocholic acid was increased in the patients, and the bile acid pool was enriched with secondary bile acids. In periods prior to cholestasis, the urinary 3 alpha OH-bile acid concentration was often elevated (greater than 50 mumoles per liter) without a clear correlation with the clinical prodromata. However, it could not be used as a predictor of cholestasis. In contrast, the postprandial rise in serum 3 alpha OH-bile acids was always grossly elevated in periods just before cholestasis. An increase both in fecal bile acid excretion as well as secondary bile acids in the bile acid pool indicated an increased spillover of bile acids into the large bowel. Cholestyramine administered directly after the first signs of cholestasis appeared to shorten an episode of cholestasis. On the other hand, withdrawal of cholestyramine in a cholestasis-free period may have resulted in an episode of cholestasis. Neither taurine supplementation for 3 and 7 weeks nor calcium phosphate, which binds sulfated bile acids in vitro, for 3 weeks could prevent an episode of cholestasis, although the latter normalized the bile acid pool composition. There is a rationale for a fat-restricted diet and cholestyramine therapy only as maintenance treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2925157 TI - The prevalence and incidence of cholecystolithiasis in patients with chronic liver diseases: a prospective study. AB - To investigate the prevalence and incidence of cholecystolithiasis in hepatitis B surface antigen-positive chronic liver diseases, a prospective study using hepatobiliary ultrasonography was conducted in 933 "healthy" persons and four groups of HBsAg-positive patients: 226 asymptomatic carriers, 73 patients with chronic active hepatitis, 77 patients with early liver cirrhosis and 124 patients with advanced liver cirrhosis. Patients with hepatocellular carcinoma or alcoholism were excluded. The prevalences of cholecystolithiasis increased along with the increasing duration and severity of chronic liver diseases, with a significant linear trend (p less than 0.001). The prevalences of cholecystolithiasis in patients with liver cirrhosis (18.5% in males, 31.2% in females) were 4 to 5.5 times higher than that of the healthy population (p less than 0.005). In addition, the linear trend of increasing prevalence with increasing age in the healthy population was not observed in patients with chronic liver diseases. On the other hand, five of the 69 patients with early liver cirrhosis were found to develop cholecystolithiasis during a mean follow-up period of 32 months. The calculated annual incidence of cholecystolithiasis was 2.6%. The results suggest that chronic liver disease, particularly liver cirrhosis, is a risk factor for cholecystolithiasis. PMID- 2925158 TI - Association between cholesterol-phospholipid vesicles and cholesterol crystals in human gallbladder bile. AB - Rapid aggregation of cholesterol-phospholipid vesicles in gallbladder bile seems to be the first event in the production of cholesterol crystals, a prerequisite for cholesterol gallstone formation. We examined the amount of these vesicles in 33 human gallbladder biles in relation to biliary lipid composition and to the presence of cholesterol crystals. Biliary microscopy detected cholesterol crystals in all 19 biles from patients with cholesterol gallstones but in none of 14 biles from patients with pigment stones. Gel chromatography was used to separate vesicles and micelles in the native bile with an eluting buffer containing 10 mM sodium cholate to prevent disruption of micellar lipids. Cholesterol, phospholipid and bile salt concentrations were measured in every fraction collected. Bile acid, phospholipid, cholesterol and total lipid concentrations were not significantly different in samples with and without cholesterol crystals. The cholesterol saturation index (1.4 +/- 0.11 vs. 1.0 +/- 0.08) was significantly (p less than 0.01) higher in biles with crystals than without crystals. Gel filtration revealed a vesicular peak in addition to micellar fraction in 18 (23.1 +/- 3.2% of total cholesterol) of the 19 biles with crystals but only in three (15.7 +/- 2.4% of total cholesterol) of 14 biles without crystals. There was no relation between biliary lipid concentration or the cholesterol saturation index and the percentage of vesicular cholesterol in biles with or without crystals. The close association of vesicles and crystals in human gallbladder bile supports the contention that vesicles are important in the initial nucleation of cholesterol monohydrate crystals. PMID- 2925159 TI - Studies on the regulation of cholesterol metabolism by low- and high-density lipoproteins in HepG2 cells. AB - The uptake and degradation of low-density lipoproteins and the esterification and synthesis of cholesterol were poorly down-regulated by low-density lipoproteins in HepG2 cells. Addition of low-density lipoproteins to the cells increased the free and esterified cholesterol in the cells. The heavier fraction of high density lipoproteins enhanced the degradation of low-density lipoproteins and cholesterol synthesis and decreased acyl CoA:cholesterol acyltransferase activity. Addition of the heavier fraction of high-density lipoproteins also caused a net efflux of cholesterol from HepG2 cells. The lighter fraction did not have any significant effect on cholesterol metabolism or cellular cholesterol level. Neither the lighter nor the heavier fractions of high-density lipoproteins were found to have any specific binding properties to HepG2 cells. PMID- 2925160 TI - D-glucaro-1,4-lactone: its excretion in the bile and urine and effect on the biliary secretion of beta-glucuronidase after oral administration in rats. AB - This experiment was designed to test the hypothesis that orally administered D glucaro-1,4-lactone might be excreted in the bile and thus suppress the activity of biliary beta-glucuronidase, which is believed to play a key role in the development of pigment gallstones. D-Glucaro-1,4-lactone, 50 to 2,600 mu moles, was fed to adult Sprague-Dawley rats which had a bile fistula and were kept in metabolic cages for bile and urine collection. A total of 21 feeding experiments were carried out. Quantitation of D-glucaro-1,4-lactone and total D-glucaric acid as the sum of D-glucaric acid and its lactones in the bile and urine involved extraction of bile with tetrahexylammonium chloride, adjustment of pH, boiling and determination of percentage inhibition of beta-glucuronidase activity. The maximal velocity of beta-glucuronidase in the bile was also determined by the enzyme kinetic method. The results showed that 11% of administered D-glucaro-1,4 lactone was excreted in the urine and only 0.2% in the bile, with D-glucaro-1,4 lactone accounting for 20% of the total excreted D-glucaric acid. The concentration and excretory rate of total D-glucaric acid and D-glucaro-1,4 lactone in the urine, but not in the bile, were proportional to the amount of D glucaro-1,4-lactone fed. The mean concentration of D-glucaro-1,4-lactone in the bile after feeding was 0.06 mM, which was capable of suppression of 75% of beta glucuronidase activity. Oral administration of D-glucaro-1,4-lactone decreased biliary beta-glucuronidase concentration, slowed bile flow rate and hence decreased biliary beta-glucuronidase secretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2925161 TI - Modulation of hepatic ferrochelatase activity by dietary manipulation of mitochondrial phospholipid fatty acyl groups. AB - Ferrochelatase is an enzyme bound to the inner mitochondrial membrane, which is important in heme biosynthesis. Activity of purified ferrochelatase is affected by the presence of certain fatty acids. In the present study, we examined whether the activity of ferrochelatase is altered by dietary manipulation of the composition of mitochondrial membrane phospholipid fatty acyl groups. Rats were fed diets containing triolein, safflower or menhaden oil as 5% (w/w) of the diet. After 3 weeks, the animals were killed and liver mitochondria were isolated. Phospholipid fatty acid composition and ferrochelatase activity were assayed in the isolated mitochondria. Marked differences were seen. The proportion of oleic acid was highest in the triolein oil-fed group, that of linoleic and arachidonic acid was highest in the safflower oil-fed group and the proportion of eicosapentaenoic acid was highest in the menhaden oil-fed group. Ferrochelatase activity was greatest in the triolein oil-fed group and lowest in the menhaden oil-fed group regardless of whether the mitochondria were intact, sonicated or sonicated and treated with Tween 20. Mixing of mitochondria from menhaden oil-fed rats with triolein oil resulted in a significant increase in ferrochelatase activity. Membrane fluidity and activities of the mitochondrial membrane enzymes succinic dehydrogenase and cytochrome oxidase did not differ among the groups. We conclude that dietary manipulation of mitochondrial membrane phospholipid fatty acyl group composition can directly modulate hepatic ferrochelatase activity. This has potential application in the treatment of protoporphyria, the genetic disorder in which ferrochelatase activity is deficient. PMID- 2925162 TI - Effect of repetitive low-dose endotoxin on liver parenchymal and Kupffer cell fibronectin release. AB - Repetitive low-dose endotoxin, at a dose which will result in endotoxin tolerance, produces a marked but transient 2- to 3-day increase in plasma fibronectin. This elevation of fibronectin appears to contribute to increased hepatic Kupffer cell phagocytic function observed with repetitive low-dose endotoxin administration. Although numerous cell types synthesize fibronectin, hepatocytes are believed to be the major cell source of fibronectin in the plasma. Since Kupffer cells also synthesize fibronectin, we sought to determine the relative contribution of hepatic Kupffer cells, as compared to parenchymal cells, to the elevation of plasma fibronectin following repetitive low-dose endotoxin administration. Kupffer cells isolated from rats previously treated for 3 consecutive days with 100 micrograms Salmonella enteritidis endotoxin released greater (p less than 0.01) amounts of fibronectin over time in culture (3, 6, 12 and 24 hr) as compared to Kupffer cells isolated from normal rats. Experiments in which fibronectin was normalized to DNA content of the cells in culture also showed similar results for fibronectin release by Kupffer cells (normal: 2.9 +/- 0.5 ng per microgram DNA per 24 hr; endotoxin-treated: 53.3 +/- 1.3 ng per microgram DNA per 24 hr). Hepatocytes from endotoxin-treated rats released less (p less than 0.01) fibronectin over time than hepatocytes isolated from normal animals. As with Kupffer cells, results for fibronectin release by hepatocytes were similar when normalized to the DNA content (normal: 190.0 +/- 9.4 ng per microgram DNA per 24 hr; endotoxin-treated: 83.3 +/- 4.2 ng per microgram DNA per 24 hr).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2925163 TI - Biochemical effects and zonal heterogeneity of peroxisome proliferation induced by perfluorocarboxylic acids in rat liver. AB - Rats were treated for 5 to 14 days with perfluoroacetate, perfluorobutyrate and perfluorooctanoate. Alterations in hepatic morphology with special reference to the peroxisomal compartment were investigated by light and electron microscopy following cytochemical staining of catalase activity with the alkaline 3,3' diaminobenzidine medium. All three compounds induced hepatomegaly and peroxisome proliferation. Perfluorobutyrate and perfluorooctanoate were found to be more active than perfluoroacetate. Perfluorooctanoate-induced peroxisome proliferation was more prevalent in centrilobular than in periportal hepatocytes. Peroxisomes in centrilobular liver cells frequently were of round shape, exhibited diameters of up to 1.5 microns and were predominantly located within smooth endoplasmic reticulum-glycogen areas. In periportal cells, however, clusters of polymorphous peroxisomes ranging from 250 to 1,100 nm in diameter were observed at the periphery of smooth endoplasmic reticulum-glycogen regions. Peroxisome proliferation was accompanied by a change of peroxisomal and mitochondrial enzyme activities, in particular an increase in peroxisomal palmitoyl-CoA oxidation. Significant alterations in the concentration of peroxisomal matrix and membrane polypeptides were also noted. Within the first 2 days, perfluorooctanoate treatment exerted a strong hypolipidemic activity and both compounds perfluorooctanoate and perfluorobutyrate raised the level of hepatic free acid soluble CoA nearly 10-fold as compared with control livers. The results suggest perfluorinated carboxylic acids to be model substances suitable to correlate biochemical and morphological parameters with the zonal heterogeneity of the peroxisomal compartment in rat liver. Due to the manifold hepatic effects, contact of humans with perfluorinated carboxylic acids or their metabolic precursors may represent a severe health risk. PMID- 2925164 TI - Vitamin B6 repletion in cirrhosis with oral pyridoxine: failure to improve amino acid metabolism. AB - This study evaluated the effect of daily oral pyridoxine supplementation in patients with cirrhosis. Eight subjects were treated with 25 mg of pyridoxine for 28 days. Before and after the supplementation period, B6 status was assessed by measuring fasting plasma vitamer levels and response to a 25 mg oral pyridoxine load. In addition, a 24-hr urine collection was analyzed during each load study for B6 metabolites. The data indicated that supplementation achieved repletion of peripheral B6 stores, as evidenced by: (i) a significant (p less than 0.005) rise in fasting plasma pyridoxal phosphate after supplementation (mean +/- S.D. = 56.8 +/- 30.5 nmoles per liter) as compared to initial levels (17.0 +/- 17.8 nmoles per liter); (ii) a higher (p less than 0.05) percentage excretion of the pyridoxine load as urinary 4-pyridoxic acid (31.0 +/- 9.3%) compared to the initial load (19.6 +/- 5.8%), and (iii) a postsupplementation area under the plasma concentration vs. time curve for pyridoxal phosphate (377 +/- 529 nmoles.hr per liter), which was decreased (p less than 0.005) from the presupplementation value (934 +/- 756 nmoles.hr per liter). The postsupplementation fasting plasma pyridoxal phosphate concentrations were within the normal range. The consequences of B6 repletion on amino acid metabolism were measured by oral protein loads (n = 4) or oral methionine loads (n = 4). No significant changes were observed for methionine or any other amino acid in regard to plasma fasting concentration, peak concentration or AUC. Although the vitamin B6 deficiency of cirrhosis was corrected by daily oral pyridoxine supplementation, there was apparently no improvement in the deranged amino acid metabolism. PMID- 2925165 TI - Changes in liver and spleen volume in alcoholic liver fibrosis of man. AB - Alcoholic liver fibrosis is a relatively common form of alcoholic liver disease in Japan. It is regarded by some investigators as a prodromal stage of alcoholic liver cirrhosis, but little is known about the volumes of the liver and spleen in this disease state. Therefore, liver and spleen volumes were measured by computed tomography in 32 patients with alcoholic liver fibrosis in comparison with 10 healthy volunteers. Patients with alcoholic liver fibrosis were divided into three subgroups (13 of Grade 1, 9 of Grade 2 and 10 of Grade 3) according to the severity of fibrosis. The volume was calculated from the sum of the area measurements of successive transverse sections of the two organs. The liver volume (mean +/- S.D.) in Grade 2 alcoholic liver fibrosis (1,281 +/- 112 cm3) was significantly (p less than 0.01) larger than in healthy volunteers (1,017 +/- 73 cm3) and in Grade 1 (1,090 +/- 157 cm3), and the liver volume in Grade 3 (1,490 +/- 132 cm3) was larger than in Grade 2 (p less than 0.01). The mean volume of hepatocytes estimated by a two-dimensional image analysis system was significantly (p less than 0.05) larger in Grade 3 than in Grade 2, and that in Grade 2 was larger than in Grade 1. The spleen volume in Grade 3 (151 +/- 40 cm3) was significantly (p less than 0.01) larger than in healthy volunteers (86 +/- 26 cm3), Grade 1 (89 +/- 38 cm3) and Grade 2 (68 +/- 19 cm3). The presumed reason for hepatic volume increase would be the ballooning of hepatocytes along with increased fibrotic component. PMID- 2925166 TI - The effect of several sex steroid hormones on the growth rate of three Morris hepatoma tumor lines. AB - Morris hepatoma 44, whose growth is sensitive to thyroid hormones and prolactin, contains specific receptors for these hormones. In the present experiments, male Buffalo rats bearing Morris hepatoma 7787 were studied to determine the effects of several sex steroid hormones. Castration 1 week postimplantation inhibited tumor growth relative to controls (-53%). Replacement with testosterone propionate (1 mg per day s.c. injection) restored tumor growth to control levels, whereas administration of testosterone (2 mg per day s.c. injection) to castrated controls resulted in significant stimulation. Testosterone administered to control animals at a dose of 1 mg per day stimulated tumor growth (62%), whereas 2 mg per day failed to do so. Progesterone (4-pregnon-3,20-dione) at doses of 125 or 250 micrograms per day (Silastic implants) had no effect on tumor growth, whereas 500 micrograms per day stimulated tumor growth relative to controls. Estrogen (17 beta-estradiol) at doses of 6, 12, or 24 micrograms per day (Silastic implants) did not influence tumor growth. Cytoplasmic testosterone receptors have been demonstrated in tumors (2.2 +/- 0.8 fmoles per mg cytoplasm), although specific cytoplasmic estrogen and progesterone receptors could not be identified in this model. In female rats bearing either Morris hepatoma 44, 7787 or 5123-D, testosterone markedly stimulated tumor growth (226, 328 and 58%, respectively, relative to controls). In conclusion, although Morris hepatoma 7787 appears to be androgen (testosterone) dependent and contains cytoplastic androgen receptors, it lacks specific cytoplasmic receptors for estrogen and progesterone and is not influenced by these hormones except at very high doses of progesterone. PMID- 2925167 TI - Immunotargeting in the diagnosis and treatment of liver cancer. PMID- 2925169 TI - Colchicine treatment of cirrhosis: questions. PMID- 2925168 TI - Impaired sulfoxidation in patients with primary biliary cirrhosis. PMID- 2925170 TI - Colchicine treatment of cirrhosis: answers. PMID- 2925171 TI - Targeted therapy for hepatic cancer: good in theory, problematic in practice. PMID- 2925172 TI - More on ascitic fluid culture technique. PMID- 2925173 TI - Selective permeabilization of the endoplasmic reticulum by monohydroxylated bile acids in liver. PMID- 2925174 TI - Microcystic meningiomas--an unusual morphological variant of meningiomas. AB - Nine cases of microcystic meningiomas, a distinct morphological variant of meningiomas, are reported. They are characterized by a vacuolated and myxomatous histological appearance with multiple cystic spaces lined by stellate-shaped tumour cells. Immunohistochemically, they shared a similar pattern of positive staining for epithelial membrane antigen and vimentin with other meningiomas. Their unusual histological features might lead to problems in differential diagnosis from other intracranial tumours, including schwannomas, chordomas, astrocytomas and angioblastic meningiomas. PMID- 2925175 TI - A case of ovarian fibromatosis with disseminated intra-abdominal fibromatosis. AB - A case of bilateral ovarian fibromatosis and massive oedema with subsequent intra abdominal fibromatosis which underwent an aggressive and fatal course is described. This is the first report of co-existence of these two conditions and the possible relationship between them is discussed. PMID- 2925176 TI - Monoclonality and polyclonality of plasma cells in Castleman's disease of the plasma cell variant. AB - Castleman's disease of the plasma cell variant observed in 21 patients was investigated morphologically and by immunohistochemistry. The male to female ratio was 2.5:1. The age ranged from 18 to 71 years (mean age 47.6 years). Histologically, the lesions were characterized by numerous, evenly distributed germinal centres ranging from large hyperplastic to small hyaline-vascular types with moderate to extensive sheets of plasma cells in between. In all cases with generalized lymph node enlargement dilated sinuses could be found. Immunohistochemical studies demonstrated a polyclonal plasma cell population in 11 of 18 lesions. Seven lesions contained a monoclonal plasma cell population, five with IgG/lambda and two with IgA/lambda; clinically, two of these patients had generalized lymphadenopathy; in none could manifestation of a plasmacytoma be found outside the lymph node lesion; only two of the seven patients exhibited a paraproteinaemia (IgG/lambda and IgA/lambda, respectively) corresponding to the Ig type of the proliferated plasma cells. Six patients with polyclonal lesions had constitutional symptoms such as fever, anaemia, polyclonal hypergammaglobulinaemia; one of these six patients manifested symptoms consistent with a diagnosis of Takatsuki syndrome. The monoclonal plasma cell type of Castleman's disease did not progress to a generalized disease. This monoclonal variant may be a lymph nodebased type of benign monoclonal gammopathy. PMID- 2925177 TI - Secretory carcinoma of the breast in adults: emphasis on late recurrence and metastasis. AB - Secretory (so-called juvenile) carcinoma of the breast, first described in children, occurs also in adult women, predominantly in the third decade. Less commonly it is seen in older age groups, up to the eighth decade. We report five patients with this tumour; one, a female aged 73, is the oldest age at which the tumour has been recorded, and one is the first report in an adult male in whom the disease recurred after 20 years, only the second recorded death attributable to this tumour type. Secretory carcinoma in adults is potentially more aggressive than in childhood. Nodal metastases are more frequent and sometimes more extensive. Recurrence of tumour after surgery developed in four of our five patients at 3, 8, 15 and 20 years. Slow growth and delayed recurrence are characteristic of many of these tumours. Death from systemic metastases is rare, but may ensue either rapidly or following a long latent period after treatment. Prolonged follow-up is needed to assess accurately the biological behaviour of this tumour. PMID- 2925178 TI - Macrophages and interdigitating reticulum cells in normal thymus and in thymoma: an immunohistochemical study. AB - The distribution and immunophenotype of macrophages and interdigitating reticulum cells were investigated on frozen sections of seven normal thymuses and 10 thymomas. In normal thymus, macrophages were mainly located in the cortex, were markedly PAM-1+/MAC+, weakly Leu-M3+ (CD14), T4+ (CD4), T9+ and OKM-1+ (CD11b). Interdigitating reticulum cells were mainly located in the medulla and were pan Leu+ (CD45), T4+(CD4+), HLA-DR+; furthermore, they were also often TAC+ (CD25) and T9+. Thymomas were composed of cytokeratin-containing epithelial cells admixed with variable proportions of T6+ (CD1a) lymphocytes. As defined by the histological features two thymomas were lymphocyte-rich, five were mixed type and three were epithelial-rich; eight thymomas were mainly composed of cortical epithelial cells and two were composed of spindle epithelial cells suggesting a medullary origin. In all cases, thymoma-associated macrophages were markedly PAM 1+/MAC+; they were numerous, and regularly distributed throughout the tumour. The density of macrophages per unit area was similar to that of the normal thymus, and was not influenced by the histological type or by the lymphocyte content of the tumour. Interdigitating reticulum cells were few and were confined to the areas of medullary differentiation. PMID- 2925179 TI - Massive pericellular collagen deposition in the liver of a young female with severe Crohn's disease. AB - We report a patient with Crohn's disease in whom repeated liver biopsies taken at surgery for the bowel disease showed progressive hepatic fibrosis of an unusual type. Dense collagen was deposited in the perisinusoidal space often surrounding individual hepatocytes. The aetiology and pathogenesis of this abnormality remain speculative. PMID- 2925180 TI - Mating call phonotaxis in female American toad: lesions of anterior preoptic nucleus. AB - Lesions of the preoptic area and immediately adjacent septal area were made in female American toads, Bufo americanus. The ability to show mating call phonotaxis (MCP) was then tested for. The intensity of MCP was found to decrease as the degree of damage to the anterior tip of the anterior preoptic nucleus (APON) increased. The APON is known to concentrate androgens and to be essential for mating calling by male anurans. Perhaps the APON is involved also in the detection of the elevated levels of prostaglandin associated with MCP. Even in lesioned toads in which phonotaxis was nearly absent, there was an occasional MCP response that seemed entirely normal. Therefore, the APON is not involved in generating or guiding the motor mechanisms of phonotaxis. PMID- 2925181 TI - Effects of ATD on male sexual behavior and androgen receptor binding: a reexamination of the aromatization hypothesis. AB - The aromatization hypothesis asserts that testosterone (T) must be aromatized to estradiol (E2) to activate copulatory behavior in the male rat. In support of this hypothesis, the aromatization inhibitor, ATD, has been found to suppress male sexual behavior in T-treated rats. In our experiment, we first replicated this finding by peripherally injecting ATD (15 mg/day) or propylene glycol into T treated (two 10-mm Silastic capsules) or control castrated male rats. In a second experiment, we bilaterally implanted either ATD-filled or blank cannulae into the medial preoptic area (MPOA) of either T-treated or control castrated male rats. With this more local distribution of ATD, a lesser decline in sexual behavior was found, suggesting that other brain areas are involved in the neurohormonal activation of copulatory behavior in the male rat. To determine whether in vivo ATD interacts with androgen or estrogen receptors, we conducted cell nuclear androgen and estrogen receptor binding assays of hypothalamus, preoptic area, amygdala, and septum following treatment with the combinations of systemic T alone. ATD plus T, ATD alone, and blank control. In all four brain areas binding of T to androgen receptors was significantly decreased in the presence of ATD, suggesting that ATD may act both as an androgen receptor blocker and as an aromatization inhibitor. Competitive binding studies indicated that ATD competes in vitro for cytosol androgen receptors, thus substantiating the in vivo antiandrogenic effects of ATD. Cell nuclear estrogen receptor binding was not significantly increased by exposure to T in the physiological range. No agonistic properties of ATD were observed either behaviorally or biochemically. Thus, an alternative explanation for the inhibitory effects of ATD on male sexual behavior is that ATD prevents T from binding to androgen receptors. PMID- 2925182 TI - Sexual differentiation in quail: critical period and hormonal specificity. AB - There is a discrepancy between results showing that male quail are demasculinized by exogenous estrogens only if the treatment is given before Day 12 of egg incubation and results showing that ovariectomy of females after hatching still affects their sexual differentiation which leads to the conclusion that female demasculinization by ovarian estrogens is a continuing process extending into posthatching life. The first experiment was performed to test different models which have been proposed to reconcile these apparently contradictory results. Male and female quail were treated with 0, 5, or 25 micrograms of estradiol benzoate (EB) on either Day 9 or Day 14 of embryonic life. Birds were castrated at the age of 4 days to avoid the confounding effects of postnatal gonadal hormones and were treated as adults with testosterone (T). Whereas EB-treatment demasculizined sexual behavior and cloacal gland growth of males when administered on Day 9, it was without effect on Day 14. This result confirms the presence of a "critical period" for sexual differentiation of behavior in embryonic life. However, the time course of sexual differentiation and the sensitivity to the demasculinizing actions of estrogens were not the same for different behavioral and morphological characteristics. Some dependent variables such as plasma levels of luteinizing hormone and crowing were still affected by the EB treatment on Day 14. These results show that the whole process of demasculinization is not retricted to the "critical period" ending on Day 12 of incubation. A second experiment was performed to determine if 5 beta dihydrotestosterone (5 beta-DHT), a metabolite of testosterone, also exerts demasculinizing effects during embryonic life. A large dose of 5 beta-DHT (2 mg/egg) had no effects on behavior and morphology in males if administered on Day 9 of egg incubation. This suggests that 5 beta-DHT, which is a steroid devoid of behavioral effects in the adult bird, is also an inactive compound as far as sexual differentiation of the quail is concerned. The high 5 beta-reductase activity which was previously identified in the hypothalamus of the embryonic quail thus probably plays a protective role. By transforming testosterone into inactive nonaromatizable androgens, it prevents male embryos from being demasculinized by their endogenous testosterone acting through aromatization. PMID- 2925183 TI - Measurements of postcoital sympathetic activity in females by means of vanillylmandelic acid. AB - Urinary vanillylmandelic acid (VMA), the final metabolite of epinephrine and norepinephrine, and creatinine (Cr) were measured 1 hr before, within an hour after intercourse, and in a 23-hr pooled sample after intercourse in 11 females. The results were compared to a group of 8 normal females who abstained from intercourse. The control VMA/creatinine ratios were significantly lower than the preintercourse values (P less than 0.01) as well as the postintercourse and 23-hr pooled postintercourse sample. This ratio, 1 hr postintercourse increased significantly (P less than 0.01) over the preintercourse values. The pooled 23-hr postintercourse sample remained high and was significantly different from preintercourse but not from the postintercourse sample. The absolute values of VMA showed relatively similar significance. This study provides objective evidence in the female for the considerable involvement of the sympathetic system during sexual intercourse. In addition, it shows that the group that was planning to have sexual intercourse, 1 hr prior to intercourse, already had VMA/creatinine ratios double over the control group. Such objective information has hitherto not been available. PMID- 2925184 TI - Photoperiodic modulation of sexual and aggressive behavior in female golden hamsters (Mesocricetus auratus): role of the pineal gland. AB - Pinealectomized female hamsters (Mesocricetus auratus) housed in a short-day photoperiod were ovariectomized and tested for hormone-induced sexual receptivity in order to investigate the role of the pineal gland in the control of behavioral sensitivity to exogenous ovarian steroid hormones (Experiment 1). Behavioral sensitivity to hormones was further investigated in females maintained in a long day photoperiod and rendered acyclic by daily administration of exogenous melatonin (Experiment 2). Female aggressive behavior was also monitored in all tests. Pinealectomy did not affect the reduced behavioral sensitivity to exogenous estrogen (E) induced by short days. These animals were also partially refractory to the effects of E when combined with low doses of progesterone. In addition, although melatonin administration mimicked the effects of short days on estrous cyclicity, the expression of hormone-dependent behaviors in these animals resembled the pattern displayed by control animals kept in long days. Thus, these findings suggest that the pineal gland plays a negligible role in the photoperiodic modulation of hormone-dependent sociosexual behaviors in female hamsters. PMID- 2925185 TI - Actions of RU 38486 on progesterone facilitation and sequential inhibition of rat estrous behavior: correlation with neural progestin receptor levels. AB - The present study examined the actions of the antiprogestin RU 38486 on progesterone (P)-induced facilitation and sequential inhibition of estrous behavior and on brain cytosol progestin receptor (PR) levels in ovariectomized, estrogen-primed (0.5 micrograms of estradiol benzoate for 3 days) female rats. RU 38486 suppressed P-facilitated receptive and proceptive responses in a dose dependent fashion when administered 1 hr prior to P. RU 38486 did not, however, block the sequential inhibitory effect of P. Indeed, when it was administered alone at a dose of 1 mg, animals were rendered behaviorally unresponsive to a P treatment 25 hr later. It is unclear whether RU 38486 is an agonist for P sequential inhibition of estrous behavior or if the apparent agonist action of RU 38486 actually results from a long-term antagonist effect. Estrogen-induced PRs remain elevated (35-55% above basal) in the hypothalamus (HYP) and preoptic area (POA) at 24 and 48 hr following the last estrogen injection. Thus P facilitation of estrous behavior is correlated with increased levels of cytosol PRs. RU 38486 reduced cytosol PRs in both brain regions to basal levels within 2 hr, and the levels remained suppressed 25 hr following the treatment. Hence there is a strong correlation between behavioral inhibition and suppressed cytosol PRs at both short (5 hr) and long (25 hr) intervals after RU 38486 administration. A P treatment which produced sequential inhibition of estrous responsiveness 24 hr later did not reduce the estrogen-induced level of cytosol PRs in either brain region. These results suggest that mechanisms in addition to induction of PRs may be necessary to ensure successful mating. PMID- 2925186 TI - Perseverative responding in male and female Wistar rats: effects of gonadal hormones. AB - Response perseveration was investigated in an experimental procedure which has previously been shown to be sensitive to pharmacologically induced behavioral perseveration and response stereotypy. Different groups of intact, gonadectomized, and gonadectomized plus chronically testosterone-treated male and female Wistar rats were exposed to this procedure in which reinforcers were randomly assigned to one of two levers in an operant chamber. One response on the lever to which the reinforcer was assigned was sufficient to produce a food pellet. Response perseveration, defined as the percentage of trials on which more than one response on the lever not selected for reinforcement was made prior to switching to the selected lever was highest in testosterone-treated subjects. Females made more responses on the lever which had been selected for food on the preceding trial, suggesting that females may be more sensitive than males to the consequences of their behavior. This behavioral difference between the sexes may be mediated by the male hormone testosterone. PMID- 2925187 TI - Reproductive behavior and LH levels of cockatiels (Nymphicus hollandicus) associated with photostimulation, nest-box presentation, and degree of mate access. AB - To determine the relative contribution of mate access and environmental cues in stimulating egg-laying and plasma luteinizing hormone (LH) secretion in cockatiels (Nymphicus hollandicus), and of mate access on nest-inspection and bowl-formation, mated pairs were permitted different degrees of mate access (full contact, auditory plus visual contact, auditory contact only, or no contact) and sequentially exposed to three environmental conditions (8L:16D without nest-box access for 6 weeks; 15L:9D without nest-box access for 3 weeks; 15L:9D with nest box access for 3 weeks). The results indicate that a high degree of mate access is essential for the performance of nesting behaviors, since birds allowed no mate access or only auditory mate access were significantly less likely to inspect the nest or form a nest-bowl. Furthermore, pairs permitted no contact, auditory contact only, or auditory and visual contact delayed nest-inspection and bowl-formation and were significantly less likely to lay eggs than pairs with total mate contact. LH levels were significantly elevated only in photostimulated females of pairs of permitted full mate and nest-box access. These results suggest that maximal sexual activity in cockatiels requires an array of behavioral and environmental cues and that a linear relationship exists between extent of social cues and sexual activity. PMID- 2925189 TI - Activation of sexual behavior in male rats by combined subcutaneous and intracranial treatments of 5 alpha-dihydrotestosterone. AB - When given peripherally, 5 alpha-dihydrotestosterone, the major androgenic metabolite of testosterone, is relatively less effective than testosterone in activating sexual behavior of castrated male rats. In order to test the possible central nervous system effects of dihydrotestosterone more directly, we castrated Long-Evans rats, gave them a behaviorally subthreshold dose of dihydrotestosterone placed subcutaneously in Silastic capsules (ScDHT), and then additionally treated the rats with intracranial implants of crystalline dihydrotestosterone (IcDHT, N = 12), testosterone (IcT, N = 12), or cholesterol (IcCHOL, N = 10) placed in the medial preoptic area. The peripheral ScDHT treatment maintained sexual organ weights of castrated males at levels comparable to those of intact males, but did not in itself significantly activate mating behavior. The addition of IcT or IcDHT to this treatment regimen significantly increased the number of males displaying mounting behavior, intromissions, and ejaculatory behavior (P less than 0.05) compared to males with IcCHOL implants. There were no significant differences between the group given IcT and the group given IcDHT. Results of this study support the hypothesis that the nonaromatizable androgen 5 alpha-dihydrotestosterone can act in the rat brain to influence male sexual behavior. In addition, these data lead us to suggest that the relative ineffectiveness of dihydrotestosterone versus testosterone when given systemically may reflect differences in bioavailability of these hormones to the brain following such treatment. PMID- 2925188 TI - Hormonal correlates of male attractiveness during mate selection in the mallard duck (Anas platyrhynchos). AB - The aims of the present study were (1) to examine if feeding condition prior to mating influences male hormone levels and behavior, (2) to evaluate the effect of age on male hormone levels, (3) to examine a possible association between male social display activity and four steroid hormones (testosterone, dihydrotestosterone, estrogen, and corticosterone), and (4) to examine if female behavior influences male hormone levels. Thirty male and fifteen female mallards were used in this study. Observations were made on a mixed flock of mallards for 10 consecutive days in autumn. Five weeks before the observations, males were randomly assigned to a feeding regime with either an unlimited food supply (UL group) or a limited food supply (L group). Males in the UL group showed significantly greater social display activity compared to the L group males. Females never incited (courted) males from the L group. Dihydrotestosterone levels were significantly higher in males showing social display activity as compared to males not showing these behavior patterns. Testosterone levels were significantly higher in males incited by females compared to males not incited by females. PMID- 2925190 TI - Planned gifts combine donations, tax strategy. PMID- 2925191 TI - CPAs call for more realistic income reporting. PMID- 2925192 TI - Software eases Agenda for Change abstracting. PMID- 2925193 TI - Physician recruitment takes center stage. PMID- 2925194 TI - Teleradiology may ease rural staffing problems. PMID- 2925197 TI - Rehabilitating injured workers is profitable. PMID- 2925196 TI - Board composition law: nuisance or benefit? PMID- 2925195 TI - CEO-board relations: an update. PMID- 2925198 TI - It will take a disaster to motivate politicians. Interview by Alden Solovy. PMID- 2925199 TI - CEO shares information with his employees. PMID- 2925200 TI - Construction: hospitals top all industries. PMID- 2925201 TI - Legislation may stabilize shaky DME industry. PMID- 2925202 TI - Computers and success: IBM exec sees the link. PMID- 2925203 TI - Inflation spurs look at foreign health systems. PMID- 2925204 TI - Changing of the guard: survival tips for CEOs. PMID- 2925205 TI - Twin Cities' tales: 10 years of managed care. PMID- 2925206 TI - Efficient generation of stable antibody forming hybridoma cells by electrofusion. AB - A variety of modified electrofusion protocols designed to improve the efficiency of hybridoma production have recently appeared in the literature. We undertook to maximize the number of antibody secreting murine hybridomas by optimizing the temperature and fusion strength parameters of the conventional electrofusion technique. Anti-DNP secreting hybridomas were generated by fusing SP2/0 to immunized mouse splenic lymphocytes using an unmodified electrofusion protocol consisting of washing in a weakly conducting sorbitol fusion medium supplemented with bovine serum albumin, calcium and magnesium ions. This was followed by dielectrophoretic alignment and application of 3 short duration, high intensity field pulses in helical chambers. Optimal efficiencies of hybridomas were generated by the application of 2000 V/cm pulses at 25 degrees C (2.45 hybridomas x 10(-4) splenocytes) and as many as 63% of resulting hybridomas secreted anti DNP monoclonal antibodies, the majority of which were IgG's. These data show that modification of the electrofusion protocol by pretreatment of fusion partners with proteolytic enzymes or the use of antigen bridging is not required for the successful and efficient production of specific monoclonal antibodies by electrofusion. PMID- 2925207 TI - The use of continuous culture to enhance monoclonal antibody production. AB - Hybridoma 14-4-4S, ATCC HB32, was grown in batch and continuous culture in an attempt to increase the production of monoclonal antibody (MAb), and to determine the adequacy of each culturing method for optimizing culture media. Various concentrations of glucose, fetal bovine serum (FBS) and serum type were studied to determine their effects on the specific growth rate (mu), the specific monoclonal antibody production rate (MPR), the maximum population density and the final MAb concentration. Attempts to optimize the culture medium using the batch method resulted in ambiguous results. However, by growing the hybridoma in a cytostat at a standardized population density of 1.0 X 10(6) cells/ml, the growth rate and MPR were found to decrease below feed concentrations of glucose and FBS of 22.5 mM and 10% (v/v), respectively. In addition, the use of the cytostat demonstrated that FBS was superior to both new born bovine serum (NBS) and Serum PlusTM (SPS). Batch cultures indicated that the production of MAb appeared to be related to the metabolic activity of the cells, and continuous culture demonstrated a direct relationship between mu and MPR. PMID- 2925208 TI - Production and characterization of a monoclonal antibody to partially purified estrogen receptor from human breast tumor. AB - A hybridoma cell line that secretes monoclonal antibody, MAb-ER-Br-1-15-4-18 is established. The MAb is highly specific for estrogen receptor (ER) from human breast tumor cells. In order to raise the antibody, the ER was first isolated from human breast tumor. Mice were immunized with the partially purified ER and the fusion of the spleen cells from the mouse, showing the highest serum titer, with the cells of the NS-1 mouse myeloma line, produced hybrid cells which continuously secreted antibodies specific for ER. Three of the hybridoma cultures which tested strongly positive were cloned using limiting dilution method and one of the cell lines was selected for further study. The recovery of the MAb from the cell culture was done by ammonium sulfate precipitation followed by dialysis and then hydroxylapatite liquid chromatography using linear gradients. The purity of the antibody was checked by polyacrylamide gel electrophoresis. The MAb was isotyped and found to be IgG1. When checked against other antigens the MAb showed a minimal cross-reactivity to ER from rabbit uterus and none to ovalbumin or rat liver ferritin. Further experiments showed that the MAb recognized the ER bound to the hormone and ER in the nucleus of breast tumor cells. PMID- 2925209 TI - An approach for characterization and purification of a human monoclonal hybridoma antibody. AB - An IgG human-human monoclonal hybridoma antibody, AML-19, reactive with human myeloid cells of non-malignant and malignant origin has been produced by fusion of blood mononuclear cells from a patient with acute myeloid leukemia (AML) and the human B-lymphoma cell line RH-L4. The monoclonal antibody (MAb) AML-19 was purified from hybridoma supernatant by primarily anion-exchange chromatography, in order to separate the AML-19 MAb from contaminating immunoglobulin (Ig), e.g. bovine Ig and MAb derived from the parental fusion partner, and followed by immunoaffinity chromatography. This purification method gave the highest yield and purity of the AML-19 MAb. The isoelectric point (pI) of the MAb was estimated to be 5. Inhibition assays indicate an apparent dissociation constant (Kd) corresponding to 4 x 10(-9) M and an affinity constant (Ka) to 2.5 x 10(8)M-1 to K562 erythroleukemia cells. Scatchard plot demonstrated a linear slope as a manifestation of monoclonality and a low number of AML-19 specific epitopes, estimated to 1500 per cell. PMID- 2925210 TI - Sexual victimization of child and adolescent patients. AB - Extrafamilial abuse of hospitalized or institutionalized patients has not often been studied. Five categories of caregivers (N = 272) reported physical, psychological and "socially acceptable" instances of abuse, with most incidents occurring one or more times per week. Abuse of children, especially sexual abuse, was singled out for further study. Case reports supplement the presentation. Implications for understanding abuse, for practice and for research are presented. PMID- 2925211 TI - The effects of the upright position during childbirth. AB - The purpose of this investigation was to replicate an earlier study to clarify and verify its findings. The 68, term primigravidae married women between the ages of 18 and 25 years were assigned to three groups: (a) one group used a 30 degree upright position with no bearing down instructions during the second stage of labor (n = 24); (b) the second group used a 30 degree upright position with bearing down instructions given during the second stage of labor (n = 22); and (c) a control group used a zero degree recumbent position with bearing down instructions during the second stage of labor (n = 22). The upright position enhanced the descent of the fetal head with a shorter duration of labor in both the first and second stages. When mothers in an upright position were left alone to bear down in response to their own bodies' urges, the second stage of labor was of shorter duration. PMID- 2925212 TI - A woman of the land. AB - This cross-cultural study presents the life history of an 85-year-old Australian woman's health, illness and care experiences. The data were obtained from interviews over a four-month period. Content analysis was used to discover domains of meaning and formulate categories. The findings are ordered according to the following cultural themes: being a woman of the land, learning to get good feelings and ways to manage unsettling times. "Hardiness" and "keenness for learning" emerge for potential consideration in nursing practice and research. PMID- 2925213 TI - Role modeling versus mentoring in nursing education. AB - Role modeling, an accepted strategy for transmitting professional attitudes and behaviors from nursing instructor to students, and mentoring, a newer strategy in nursing education, are compared and contrasted. Possibilities for research and implications are discussed. PMID- 2925214 TI - Torture: a nursing concern. AB - Survivors of torture report that their tormentors have included physicians and nurses. Such misuse of medical and nursing knowledge to engage in unconscionable acts is unethical, unprofessional and a violation of human rights. Torture and its use, ways in which health professional participate and steps taken by nursing toward its prevention are discussed. PMID- 2925216 TI - The ethics of nursing rhetoric. PMID- 2925215 TI - U.S. and Australian nurses' attitudes and beliefs about the good death. AB - The purpose of this study was to ascertain the attitudes and beliefs of nurses in Australia and the United States regarding aspects of passive euthanasia, or the "good death." Two foci guided the study: (a) the possible discrepancies that these nurses might perceive between what they thought would be done in a given clinical situation and what they thought ought to be done, and (b) the possible differences and similarities between the American and the Australian nurses. Responding to the 8 vignettes, 30 American and 32 Australian nurses took part in the study. The lack of agreement between the Australian and American nurses on issues of euthanasia reflects differences in the health care system; the general social position of nursing as a profession; the relationship among health professionals, patients and families, which serves as the context for definition of ethical duties and patient rights; and the role of the law in health care decisions. PMID- 2925217 TI - Devaluation of biological knowledge. PMID- 2925218 TI - [Roferon-A (interferon alfa-2a) permitted for AIDS-associated Kaposi's sarcoma by the BGA]. PMID- 2925219 TI - [Yeasts: cause of infections of the respiratory tract?]. AB - Poor data are given in literature on the rate and concentration of yeasts on mucous membranes of the respiratory tract. Our data show a rate of lower than 0.2% (only concentrations of 10(4)-10(5) detected). In contrast to this low colonization rate, a percentage of higher than 20% can be detected in patients on intensive care units. The aetiologic role of yeasts in pneumonia and bronchitis can be evaluated more easily, if candida is not only found in a single tracheal or bronchial secretion, but in follow-up specimens and if yeasts can be detected in blood culture, urine, or from other mucous membranes. Our own experience underlines the value of the new tests for candida antigens: a titer higher than 1:4 is a strong hint for fungaemia. PMID- 2925220 TI - [Therapy of pancreatic carcinoma with the monoclonal antibody BW 494/32: first clinical results]. AB - In a phase-I clinical trial the monoclonal antibody BW 494/32 was administered to 18 patients with advanced pancreatic cancer of ductal origin. This murine immunoglobulin mediates an ADCC. The majority of patients tolerated this treatment without any side effects. There were no tumor remissions. 12 patients showed a progression of their pancreatic carcinoma after therapy. A stable course of the disease was observed in 6 patients for at least 3 months after therapy. PMID- 2925222 TI - [Infections of the lower respiratory tract]. PMID- 2925221 TI - [The treatment of solid tumors with monoclonal antibodies]. AB - Patients with B-cell lymphomas, gastrointestinal tumors and melanomas were treated in pilot and phase-I clinical studies with monoclonal antibodies directed to tumor-associated antigens in recent years. Side effects of this new treatment approach were minor. Tumor regressions were observed in all three groups of tumors. PMID- 2925223 TI - Characterization of the spontaneous autoimmune (anti-erythrocyte) response in NZB mice using a pathogenic monoclonal autoantibody and its anti-idiotype. AB - A monoclonal anti-mouse RBC antibody (G-8) has been prepared that appears to represent a pathogenic autoantibody related to those that arise spontaneously in aging NZB mice and which cause autoimmune haemolytic disease (AIHD). When G-8 producing hybridoma cells were grown as tumours in BALB/c mice, the mice developed AIHD characterized by a decrease in the number of erythrocytes (haematocrit) and the development of Coombs-positivity. An anti-idiotypic antibody (E8) was prepared against G-8 and was found to recognize an idiotypic determinant present on most autoantibody-forming cells derived from old (Coombs positive) NZB mice. The results suggest that the IgM autoantibody response of NZB mice to self-erythrocytes is restricted to a limited number of clones, most of which express the G-8 idiotype. PMID- 2925224 TI - Cellular basis of an auto-anti-allotypic mechanism for the maintenance of chronic allotype suppression in the rabbit. AB - Immunocytochemical identification of antibody-forming cells (AFCs) in situ was used to test the hypothesis that the maintenance of chronic allotype suppression in heterozygous rabbits is the result of an autoimmune B-cell-mediated response. Appreciable numbers of B cells with antibody activity directed against the suppressed allotypic determinant were found in spleen and bone marrow sections of all chronically suppressed rabbits examined. Appropriate double-staining was used to determine that such cells were of the non-suppressed allotype. These cells were indistinguishable from anti-allotypic AFCs found in larger numbers in spleens of normal heterozygous rabbits that had been immunized against a heterologous allotypic determinant. Auto-anti-allotypic AFCs were not found in suppressed rabbits less than 8 week old, nor were they found in normal (non suppressed) heterozygous rabbits or chimeric rabbits formed by the injection of histocompatible but allotype-mismatched lymphoid cells at birth. The findings reported here support the hypothesis that the long-term maintenance of allotype suppression in the rabbit may result from the suppressive activities of autoimmune B cells. It is suggested that the suppression of an allotype during the first few weeks of life could result in a loss of tolerance to a self determinant. The kinetics of auto-anti-AFC production support this idea in showing that such cells are generated following the decline of the antibody used to induce suppression. The triggering event may be the emergence of B cells expressing the previously suppressed gene product. PMID- 2925225 TI - Inhibition of immune haemolysis by a serum factor found in C3-deficient subjects. AB - A serum factor, which inhibits haemolysis of the buffer control used in a C3 haemolytic assay, was found in a C3-deficient subject (C3D). Since the buffer control consisted of EAC142, C5 and C6-9 reagent (C6-9R, prepared by treatment of guinea-pig serum with KSCN and hydrazine hydrate), the factor seems to be an inhibitor of C3-independent immune haemolysis. Gel filtration and CM cellulose column chromatography of C3D serum suggested that the inhibitor may be C8. The inhibition was not observed in C8-depleted C3D serum. Furthermore, isolated C8 was found to inhibit haemolysis of EAC142 by C5 and C6-9R in a dose-dependent fashion. Thus, C8 was found to be an inhibitor of C3-independent immune haemolysis in the assay. Further studies revealed that C8 also inhibits haemolysis of EAC142 by C3, C5 and C6-9R (C3 assay system) or that of EAC1423 by C5 and C6-9R (C5 assay system), indicating that C3 or C5 haemolytic activity can be underestimated by the presence of C8 in a sample. C8 did not inhibit haemolysis in the assay system when isolated C6-C9 of human origin were used, but did inhibit haemolysis when isolated C6-C9 of guinea-pig origin was used instead of C6-9R. Thus, it was suggested that the incompatibility of human C8 with guinea pig C6-C9 might be responsible for this phenomenon. Additional experiments for the mechanism clearly showed that human C8 inhibits the haemolysis of EAC1-7 (EA bearing human C1-C5 and guinea-pig C6 and C7) by guinea-pig C8 and C9 by binding to EAC1-7 prior to guinea-pig C8. PMID- 2925226 TI - Complement activation in human lymphoid germinal centres. AB - The presence of complement activation products has been studied in morphologically normal human lymphatic tissue from tonsil, spleen and lymph node. Newly established monoclonal antibodies (mAbs) with reactivity against the C4 cleavage fragments C4a, C4b, C4c and C4d were applied on cyrostat sections in the indirect immunoperoxidase staining technique. Irrespective of organ type, C4d activation product could be detected in germinal centres of all secondary lymphoid follicles. To substantiate this finding, the complete sequence of complement activation products was investigated by a series of mono- and polyclonal antibodies to the complement proteins C1, C2, C3, factor B, C5, C9 to C5b-9 neoantigens and to the regulatory complement proteins C4 binding protein (C4bp), factor I, factor H and properdin. Similar to C4d, all secondary follicles exhibited a strong staining reaction for C3d antigens restricted to germinal centres. At the same site, albeit with distinctly weaker intensity, components of the membrane attack complex (MAC) C5b-9 were found. The simultaneous deposition of C1, C4b and C4bp in certain germinal centres indicates that complement activation is induced via the classical pathway. Concomitant deposition of IgM suggests IgM-antigen complexes that have been trapped on follicular dendritic cells (FDC) during normal immune response as the most likely candidates for activators of the classical pathway. Our data demonstrate that human lymphoid germinal centres as important sites of immune regulation closely interrelate with the complete cascade of complement-activation products, including the membrane attack complex (MAC). PMID- 2925227 TI - Simulation of parasite-induced gut hypersensitivity: implications for vaccination. AB - Antigenic challenge of jejunum from rats infected with Trichinella spiralis evokes a biphasic pattern of epithelial Cl- secretion, as measured in vitro by electrophysiological methods. Peaks of secretion occur at approximately 1.5 and approximately 5.0 min post-challenge. Challenge of jejunum from hosts passively immunized with serum containing anti-Trichinella anaphylactic antibody evokes the late phase but not the early phase of Cl- secretion. Since the early phase is mediated by 5-hydroxytryptamine and histamine from mast cells, we hypothesized that the failure to express that phase was due to a decrease in mast cell-derived mediators secondary to a deficiency in mucosal mast cell numbers. The hypothesis was tested by correlating mast cell numbers with patterns of antigen-induced Cl- secretion using several immunization regimes. Rats actively immunized by infection produced anti-Trichinella IgE and had a mucosal mastocytosis. Rats passively sensitized with serum containing anti-Trichinella IgE had normal numbers of mast cells in their mucosa. Inducing mastocytosis in rats, by infecting them with Nippostrongylus brasiliensis prior to passive sensitization with anti-Trichinella serum, primed for the expression of a biphasic Cl- secretory response upon subsequent challenge with Trichinella antigen. Rats actively sensitized by injection with Trichinella antigen elicited an IgE response without mastocytosis and expressed only the late phase of antigen induced Cl- secretion. Results (i) support our hypothesis, (ii) emphasize the importance of the cellular state of the mucosa in the functional expression of local anaphylaxis; and (iii) provide a physiological explanation for the general failure of vaccination and passive sensitization to induce functional immunity equivalent to that induced by natural infection. PMID- 2925228 TI - Two types of sheep Peyer's patches: location along gut does not influence involution. AB - In sheep, and some other species, there is evidence of two types of Peyer's patches (PPs), the ileal PP, which extends 150 cm along the terminal ileum, and the jejunal PPs distributed throughout the rest of the small intestine. The two types differ significantly in their histology, ontogeny and the extent of lymphocyte traffic. Another intriguing difference is that the ileal PP involutes about the time of puberty whereas the jejunal PPs function throughout life. This study shows that the differences in PP lifespan is not related to their specific location in the small intestine. Surgery was done at 1-2 months of age to transpose lengths of ileal PP into the jejunum, also, PP-containing lengths of jejunum were transposed into the midst of the ileal PP. Examination at age 12-16 months showed that ileal PP transposed into jejunum had involuted at the same rate as normally sited ileal PP. Also, jejunal PPs transposed into the ileum had not involuted unlike the surrounding ileal PP. It was concluded that the difference in lifespan of the two PPs were not related to the local microenvironment created by gut function, but may be inherent to the PP itself. PMID- 2925230 TI - Chemotactic activity of lymphotoxin and tumour necrosis factor alpha for human neutrophils. AB - Lymphotoxin (TNF beta) and tumour necrosis factor alpha (TNF alpha) stimulate locomotion and chemotaxis of human blood neutrophils as measured in three assays. Both cytokines stimulate morphological polarization of neutrophils in suspension; both stimulate locomotion of neutrophils into micropore filters; both cause orientation of neutrophils towards a gradient source. Orientation in a gradient suggests a chemotactic effect. The action of both cytokines is similar but is not as strong as that of formyl peptide used as a positive control. Myelomonocytic cell lines (U937 and HL-60) develop responsiveness to formyl peptides on maturation but not to TNF alpha or beta. PMID- 2925229 TI - Site-directed differences in the immune response to the fetus. AB - Major differences in the maternal immune response to the fetus were observed in the placentomes and in the interplacentomal regions of the pregnant sheep uterus. Firstly, fewer lymphocytes were detected in the placentomes compared to the interplacentomal regions and to non-pregnant uterine tissue (Lee, Gogolin-Ewens & Brandon, 1988). Secondly, a large population of CD45R+ granulated lymphocytes was uniformly distributed in the interplacentomal uterine epithelium throughout pregnancy but never in the syncytial layer of the placentomes. Thirdly, monoclonal antibodies specific for the CD5 antigen consistently stained the endothelium of blood vessels within the placentomes but never blood vessels in the interplacentomal areas. Finally, OLA class I antigens were present on the interplacentomal uterine epithelial cells and on the maternal stromal cells, but no staining of the trophoblast or syncytium was observed. These observations suggest that different mechanisms to prevent immune rejection of the fetus may operate in the placentomes where trophoblast invasion of the maternal tissue occurs compared to the interplacentomal regions. PMID- 2925231 TI - Sequence analysis of HLA class II domains: characterization of the DQw3 family of DQB genes. AB - HLA class II allelic variants within the DQw3-related family of genes carry distinct allo-specificities and have been implicated in specific HLA-disease associations, such as insulin-dependent diabetes mellitus. To investigate the nucleotide variations which characterize DQw3 genes, we applied a novel cDNA cloning strategy that uses a single-stranded vector/primer system to facilitate DNA sequencing of allelically variable gene families. Using a DQB-specific primer sequence and M13 bacteriophage as the cloning vector, direct cloning and sequencing of multiple DQB genes was performed without the need for second strand synthesis or for subcloning. Sequence analysis from eight lymphoblastoid cell lines selected to represent different ethnic backgrounds revealed three DQw3 related DQB genes, DQB3.1, 3.2, and 3.3, corresponding to the newly designated HLA-DQw7, w8, and w9 specificities, respectively. An unusual Pro-Pro couplet at codons 55-56 is characteristic of all DQw3-positive sequences and may be contributing to the broad DQw3 allospecificity. Comparisons among ethnically disparate DQw3-related sequences showed no additional expressed or silent nucleotide substitutions among these DQB alleles. Thus, polymorphism within the DQw3 family of genes appears to be extremely limited, with a paucity of nucleotide variations accumulated by evolutionary distance. PMID- 2925232 TI - NH2-terminal amino acid sequence analysis of Qa-2 alloantigens. PMID- 2925233 TI - Biochemically defined polymorphism of bovine MHC class II antigens. PMID- 2925234 TI - Blunted pressure natriuresis in the Brattleboro diabetes insipidus rat. AB - Antidiuretic hormone is known to stimulate the renal synthesis of prostaglandins. These autacoids, in turn, modulate the pressure natriuresis phenomenon. Accordingly, the present study was done to test the hypothesis that, in the absence of antidiuretic hormone and antidiuretic hormone-dependent prostaglandin synthesis, the pressure natriuresis response is blunted. Experiments were performed on Brattleboro diabetes insipidus rats (n = 7) and Long Evans control rats (n = 14). A change in perfusion pressure in the Long Evans rats from 89.3 +/ 1.0 to 108.7 +/- 1.1 mm Hg (p less than 0.05) was associated with significant increases in the fractional excretion of sodium (1.1 +/- 0.2 to 2.3 +/- 0.3%) and the urinary prostaglandin excretion (32.6 +/- 6.8 to 56.6 +/- 10.0 pg/min). In contrast, a similar change in perfusion pressure in the diabetes insipidus rat from 88.6 +/- 1.4 to 106.2 +/- 1.5 mm Hg (p less than 0.05) resulted in no significant increases in either sodium or prostaglandin excretions. Treatment of a third group of diabetes insipidus rats (n = 9) with 1-desamino-8-D-arginine vasopressin (1 microgram/day) restored the natriuretic response to increases in renal perfusion pressure. Treated diabetes insipidus and Long Evans control rats had comparable natriuretic responses to increases in renal perfusion pressure. Untreated diabetes insipidus rats, on the other hand, had blunted responses. In summary, the pressure natriuresis response in diabetes insipidus rats is blunted compared with Long Evans control rats. We conclude that antidiuretic hormone is necessary for the complete expression of the pressure natriuresis response. PMID- 2925235 TI - Clonidine-specific antisera recognize an endogenous clonidine-displacing substance in brain. AB - An endogenous substance in brain, clonidine-displacing substance, binds to the same receptor populations as clonidine and is biologically active. Since receptor binding sites can be modeled by using specific antiligand antibodies, we tested the hypothesis that polyclonal antibodies raised in rat and rabbit against the clonidine analog p-aminoclonidine coupled to hemocyanin would recognize compounds structurally related to clonidine, including clonidine-displacing substance. Binding to anti-p-aminoclonidine antibodies was examined by using a competitive radioimmunoassay with tritiated p-aminoclonidine as the radioligand. Central vasodepressor agents that, like clonidine, are known to bind with high affinity to both imidazole sites and alpha 2-adrenergic receptors in brain inhibited radioligand binding to anti-p-aminoclonidine antibodies. All of these agents contain imidazol(in)e and phenyl ring moieties as part of their chemical structures (e.g., oxymetazoline); a number of other compounds without one or both of these rings failed to cross-react with the antisera. Clonidine-displacing substance, partially purified from bovine brain, also inhibited specific radioligand binding to anti-p-aminoclonidine antibodies. The inhibition was dose dependent and high affinity (IC50, 4 Units). The endogenous substance had no effect on the apparent affinity of the antibodies for the radioligand, but blocked a specific number of binding sites. Immunoprecipitation experiments showed that authentic clonidine-displacing substance, that which displaces tritiated p-aminoclonidine binding to membrane receptors, is recognized by anti-p aminoclonidine antibodies. We conclude that a unique subset of structural determinants required for ligand interaction with both imidazole and alpha 2 adrenergic receptors is critical for binding to anti-p-aminoclonidine antibodies, and that since clonidine-displacing substance is recognized by highly clonidine specific antisera, it may also contain these determinants within its structure, namely the imidazol(in)e and phenyl ring systems. PMID- 2925236 TI - Distribution of sodium-lithium countertransport and blood pressure in Caucasians five to eighty-nine years of age. AB - Case-control studies suggest that increased erythrocyte sodium-lithium countertransport may predict increased susceptibility to the development of essential hypertension. To characterize interindividual variation in sodium lithium countertransport and its relation to blood pressure levels in the general population, we studied 1,475 Caucasians between 5 and 89 years of age (711 males and 764 females) ascertained through 266 households with children in the schools of Rochester, Minnesota. Individuals who were taking antihypertensive agents or combinations of estrogen and progesterone were not included in the sample. A third-order polynomial regression on age accounted for only a small fraction of variability in sodium-lithium countertransport (2.8% in males, p less than 0.001; 2.1% in females, p less than 0.01), whereas a fourth-order regression on age accounted for a large proportion of variability in systolic blood pressure (45.7% in males, p less than 0.001; 52.5% in females, p less than 0.001) and diastolic blood pressure (39.8% in males, p less than 0.001; 33.0% in females, p less than 0.001). Mean sodium-lithium countertransport was higher in males than females at all ages; but the rank order of male and female means for systolic and diastolic blood pressure was age dependent. Positively skewed distributions for age-, height-, and weight-adjusted sodium-lithium countertransport in male and female cohorts between 5-19.9, 20-49.9, and 50-89.9 years of age were explained significantly better by postulating a mixture of two partially overlapping sodium lithium countertransport distributions rather than a single normal distribution (p less than 0.01). Among men in the 20-49.9-year-old cohort, adjusted sodium lithium countertransport values in the upper distribution were associated with higher systolic and diastolic blood pressure (mean +/- SD) than values in the lower distribution (for systolic blood pressure: 115 +/- 11 vs. 111 +/- 11 mm Hg, p less than 0.07; for diastolic blood pressure: 71.2 +/- 8.0 vs. 68.4 +/- 8.6 mm Hg, p less than 0.08). Among females in the 50-89.9-year-old cohort, adjusted sodium-lithium countertransport values in the upper distribution were associated with significantly greater diastolic blood pressure than values in the lower distribution (77 +/- 10 vs. 70 +/- 9 mm Hg, p less than 0.03).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2925237 TI - Resistance to infection in murine beta-thalassemia. AB - Clinical evidence suggests that individuals with chronic iron overload may be at increased risk of bacterial infection. We studied this question by using a unique model in which mice homozygous for a deletion in the gene encoding for the beta major globin develop moderate anemia, splenomegaly, and tissue iron overload, a syndrome similar to beta-thalassemia in humans. Mice heterozygous for the gene deletion were phenotypically normal. Homozygous mice were significantly more susceptible to infection with Listeria monocytogenes than were heterozygous mice (P less than 0.01). This increased susceptibility was associated with a greater number of organisms in the liver and spleen than was found in heterozygous mice (P less than 0.05). However, histologic studies demonstrated similar inflammatory responses within these organs in homozygous and heterozygous mice. The increased susceptibility of homozygous mice to infection with L. monocytogenes was not seen when homozygotes were immunized with a low dose of L. monocytogenes. Although the results were not as striking as with L. monocytogenes, homozygous mice were also found to be more susceptible to infection with Salmonella typhimurium than were heterozygous mice (P less than 0.05). Splenic mononuclear cells from homozygous mice demonstrated less responsiveness in vitro to the mitogens concanavalin A and phytohemagglutinin than did those from heterozygotes (P less than 0.05). These data suggest that there is a generalized defect in innate immunity in homozygous mice which makes them more susceptible to infection by L. monocytogenes and S. typhimurium. The site of this immunological defect is not known but is most likely in the mononuclear phagocyte and may be due to tissue iron overload. PMID- 2925238 TI - DNA and protein sequence homologies between the adhesins of Mycoplasma genitalium and Mycoplasma pneumoniae. AB - Mycoplasma genitalium and Mycoplasma pneumoniae are morphologically and serologically related pathogens that colonize the human host. Their successful parasitism appears to be dependent on the product, an adhesin protein, of a gene that is carried by each of these mycoplasmas. Here we describe the cloning and determine the sequence of the structural gene for the putative adhesin of M. genitalium and compare its sequence to the counterpart P1 gene of M. pneumoniae. Regions of homology that were consistent with the observed serological cross reactivity between these adhesins were detected at both DNA and protein levels. However, the degree of homology between these two genes and their products was much higher than anticipated. Interestingly, the A + T content of the M. genitalium adhesin gene was calculated as 60.1%, which is substantially higher tham that of the P1 gene (46.5%). Comparisons of codon usage between the two organisms revealed that M. genitalium preferentially used A- and T-rich codons. A total of 65% of positions 3 and 56% of positions 1 in M. genitalium codons were either A or T, whereas M. pneumoniae utilized A or T for positions 3 and 1 at a frequency of 40 and 47%, respectively. The biased choice of the A- and T-rich codons in M. genitalium could also account for the preferential use of A- and T rich codons in conservative amino acid substitutions found in the M. genitalium adhesin. These facts suggest that M. genitalium might have evolved independently of other human mycoplasma species, including M. pneumoniae. PMID- 2925239 TI - Oral administration of a streptococcal antigen coupled to cholera toxin B subunit evokes strong antibody responses in salivary glands and extramucosal tissues. AB - Generation of local and systemic immune responses by the oral administration of antigens is frequently inefficient, requiring large quantities of immunogens and yielding only modest antibody responses. In this study, we have demonstrated that oral administration of microgram amounts of Streptococcus mutans protein antigen I/II covalently coupled to the B subunit of cholera toxin elicits vigorous mucosal as well as extramucosal immunoglobulin A and G antistreptococcal antibody responses in mice. These responses were manifested by the presence of large numbers of antibody-secreting cells in salivary glands, mesenteric lymph nodes, and spleens and by the development of high levels of circulating antibodies. This novel immunization strategy may find broad application in the construction of oral vaccines for the control of infectious diseases caused by pathogens encountered at mucosal and extramucosal sites. PMID- 2925240 TI - Modulation of the immune response to pneumococcal type 14 capsular polysaccharide protein conjugates by the adjuvant Quil A depends on the properties of the conjugates. AB - Streptococcus pneumoniae type 14 capsular polysaccharide-bovine serum albumin (S14PS-BSA) conjugates were prepared by water-soluble-carbodiimide-mediated condensation with or without the use of N-hydroxy-sulfosuccinimide. The immunogenicities of the capsular polysaccharide (S14PS) and of the conjugates were studied in (CBA/N x BALB/c)F1 mice and in female BALB/c mice. The response in these mice indicates that S14PS could be classified as a thymus-independent type 2 antigen. Coupling of S14PS to BSA improved the immunogenicity of this polysaccharide, and an immunoglobulin G memory response was evoked. Conjugation with N-hydroxysulfosuccinimide resulted in a product with a higher polysaccharide/protein ratio. This conjugate induced a greater immune response than did the classical conjugate. Quil A enhanced the immune response to S14PS and to most S14PS-BSA conjugates. The enhancement of the immune response to the conjugates seemed to depend on the coupling procedure. Our results indicate that for the construction of immunostimulating complexes based on polysaccharide or oligosaccharide-protein conjugates, attention should be paid to the degree of cross-linking of the antigens involved. PMID- 2925241 TI - Production of a monoclonal antibody specific for Mycobacterium avium and immunological activity of the affinity-purified antigen. AB - Three hybridomas which secrete antibodies to Mycobacterium avium were obtained by the fusion of p3u1 myeloma cells with spleen cells of mice immunized with M. avium culture sonicate. The reactivity of these monoclonal antibodies was determined in 16 species of mycobacteria by an enzyme-linked immunosorbent assay. An antibody, designated Avi-3, reacted only with M. avium and not with the reference strains of the other 15 species of mycobacteria tested, including M. intracellulare, M. paratuberculosis, and M. lepraemurium. Specificity of the antibody was confirmed by assay, using a specific DNA probe of M. avium complex in 29 M. avium complex isolates. An antigen was purified from M. avium culture sonicate on a monoclonal antibody Avi-3-coupled affinity column. The purified antigen gave a single band (molecular size, about 27 kilodaltons) upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The antigen Avi-3 showed strong skin test activity in guinea pig preimmunized with heat-killed M. avium but not in those sensitized with heat-killed M. intracellulare or M. bovis BCG. Purified protein derivative elicited positive skin reactions in all the immunized guinea pigs. When heat-killed M. avium was used as the immunogen, strong lymphoproliferative responses were observed in cultures stimulated with the antigen Avi-3. These results suggest that M. avium-specific antigen Avi-3 may facilitate the diagnosis of mycobacterial infections. PMID- 2925242 TI - Protective efficacy of protein A-specific antibody against bacteremic infection due to Staphylococcus aureus in an infant rat model. AB - Staphylococcal protein A (SpA) is a potent antiphagocytic component of the cell wall of most pathogenic Staphylococcus aureus strains. We studied the in vitro opsonophagocytic and in vivo protective activities of rabbit immunoglobulin G (IgG) antibody to purified SpA obtained from two unencapsulated S. aureus strains (Cowan I and 17A). Postimmune serum contained high titers of specific IgG to SpA, as measured by a modified enzyme-linked immunosorbent assay that blocked nonspecific binding of IgG to SpA. In vitro, both S. aureus strains were efficiently phagocytosed and killed by polymorphonuclear leukocytes in the presence of nonimmune sera and complement. With one strain (Cowan I), opsonophagocytosis was significantly enhanced in the presence of SpA antibody, but with the other strain (17A), killing was significantly decreased with immune serum. We then evaluated the potential protective benefit of SpA antibody in preventing S. aureus bacteremia in infant rats. Two-day-old rats received saline or various doses of SpA antiserum and were challenged subcutaneously 1 day later, but even the highest levels of antibody did not significantly reduce mortality, bacteremia or metastatic infection to lungs or liver (frequency or magnitude). This lack of protective efficacy was not related to a failure of SpA F(ab')2 to bind to cell surface-exposed epitopes, since F(ab')2 fragments prepared from hyperimmune serum bound avidly to the whole organism in an enzyme-linked immunosorbent assay. PMID- 2925243 TI - Campylobacter pylori virulence factors in gnotobiotic piglets. AB - Thirty-three gnotobiotic piglets from four litters were challenged with motile and nonmotile strains of Campylobacter pylori. The most motile strain, 26695, was the most virulent, with a 100% infection rate. The least motile strain, Tx30a, was the least virulent, with an infection rate of only 17%. Strain 60190 was weakly motile and had intermediate virulence, with an infection rate of 40%. Strains recovered from piglets were more motile than the challenge strains. The challenge strains also differed in cytotoxin production. The least virulent strain, Tx30a, was nontoxigenic, while the other two strains produced high levels of cytotoxin. Thus, virulence of C. pylori for gnotobiotic piglets correlated very well with motility and not as well with cytotoxin production. PMID- 2925244 TI - Purification and chemical characterization of a cholera toxin-cross-reactive cytolytic enterotoxin produced by a human isolate of Aeromonas hydrophila. AB - A bacterial protein toxin possessing hemolytic, enterotoxic, and cytotoxic activities as well as cross-reactivity to cholera toxin was purified from culture filtrates of a human diarrheal isolate of Aeromonas hydrophila (SSU). This cytolytic enterotoxin was purified by ammonium sulfate precipitation, hydrophobic chromatography using phenyl-Sepharose, anion-exchange chromatography on DEAE-Bio Gel A, and size-exclusion high-performance liquid chromatography. The factor was a single polypeptide with an apparent molecular weight of 52,000 as determined by polyacrylamide gel electrophoresis. Automated amino acid sequence analysis confirmed that the toxin was a single chain and established a 25-residue N terminal segment which was identical to that of aerolysin purified from culture supernatants of A. hydrophila isolate Ah65 originally obtained from rainbow trout as reported by Howard et al. (S. P. Howard, W. J. Garland, M. J. Green, and J. T. Buckley, J. Bacteriol. 169:2869-2871, 1987). However, the amino acid compositional analysis of the toxin produced by our human isolate (SSU) differed significantly from that of the Ah65 isolate. Taken together, these results strongly indicated that several toxic phenomena associated with A. hydrophila (SSU) culture filtrates, including hemolysis, cytotoxicity, and enterotoxicity as well as cross-reactivity to cholera toxin, all can occur on a single polypeptide. In addition, these results underline the fact that although aerolysin-related toxins isolated from culture filtrates of A. hydrophila are biologically similar, significant chemical and immunological differences may exist between toxins produced by individual isolates. PMID- 2925245 TI - Bioactivity and immunological characterization of a cholera toxin-cross-reactive cytolytic enterotoxin from Aeromonas hydrophila. AB - A cytolytic enterotoxin of molecular weight 52,000 was isolated and purified from culture supernatants of a human diarrheal isolate (SSU) of Aeromonas hydrophila. The toxin reacted with cholera antitoxin when tested in an enzyme-linked immunosorbent assay and by Western blot (immunoblot) analysis. The appearance of cytotoxic and hemolytic activities in culture supernatant occurred simultaneously 8 h after the initial inoculation of the culture. Loss of hemolytic activity and cholera toxin cross-reactivity was correlated with heat and pH inactivation. Homologous antibodies neutralized the cytotoxic and hemolytic activities associated with the toxin, but cholera antitoxin did not neutralize these activities. The toxin also possessed enterotoxic activity as demonstrated by fluid accumulation in rabbit ligated intestinal loops. When purified cytolytic enterotoxin was injected intravenously into mice, death occurred within 2 min, whereas mice injected with whole cells or sonicated cell fragments died after several hours or days. Results from 51Cr release experiments demonstrated that the cytolytic enterotoxin had significant membrane-damaging capability. These results indicated that the cytolytic and enterotoxic activities expressed by the described A. hydrophila toxin may contribute significantly to the pathogenesis of disease associated with A. hydrophila. PMID- 2925246 TI - Differential clearance and host-pathogen interactions of YopE- and YopK- YopL- Yersinia pestis in BALB/c mice. AB - This study characterized infections in BALB/c mice by the nonpigmented Yersinia pestis KIM and its derivatives lacking the low-Ca2+-response virulence plasmid pCD1 or failing to express selected yersinial outer membrane proteins (YOPs). The parent Y. pestis showed net growth in the spleen by 2 h and in the liver after 7 h; exponential growth in both the liver and spleen culminated in death of the mice starting on day 4, with total bacterial numbers of less than 10(8) in the blood, liver, and spleen together. The histopathology progressed from microabscesses to extensive coagulative necrosis unaccompanied by further immigration of inflammatory cells. This, together with the relatively low bacterial numbers, suggests a toxigenic mechanism. YopE- or YopK- YopL- yersiniae were cleared from the spleen but grew in the liver after an initial lag. Their growth was curbed after 1 to 2 days and entered a plateau that lasted 5 to 6 days; viable numbers then decline rapidly. This suggests that these Yop- mutations distinguish, at least kinetically, between host responses in liver and spleen. Both strains caused acute inflammation in liver that evolved into structured lesions surrounded by progressively mononuclear inflammation suggestive of a granulomatous response. Accordingly, YOP E and YOPs K and L are necessary in the early days of the infection for net growth in spleen and prolonged growth in the liver; their absence is reflected morphologically by the emergence of cell-mediated immunity in the liver. The YopE- and YopK- YopL- mutants bound only slightly increased amounts of C3, suggesting that YOPs E, K, and L are protective through mechanisms other than interfering with the binding of complement. PMID- 2925247 TI - Tumor necrosis factor alpha-induced pulmonary vascular endothelial injury. AB - Tumor necrosis factor alpha (TNF-alpha) mediates components of the acute-phase response, stimulates granulocyte metabolism, and induces endothelial cell surface changes. We studied whether human recombinant TNF-alpha (rTNF-alpha) could increase pulmonary edema formation and pulmonary vascular permeability. Rabbits preinfused with 125I-albumin were administered rTNF-alpha or saline. Animals were sacrificed, and lung wet/dry weight ratios as well as bronchoalveolar lavage fluid and plasma 125I activities were determined. rTNF-alpha increased lung wet/dry weight ratios by 151% (P less than 0.02) and bronchoalveolar lavage fluid/plasma 125I activity ratios by 376% (P less than 0.01) compared with values for saline controls. Electron microscopy of lung sections demonstrated endothelial injury, perivascular edema, and extravasation of an ultrastructural permeability tracer. To demonstrate that rTNF-alpha could directly increase pulmonary vascular endothelial permeability in vitro, we studied albumin transfer across cultured porcine pulmonary artery endothelial cell monolayers. rTNF-alpha induced time-dependent dose-response increments in transendothelial albumin flux in the absence of granulocyte effector cells. These observations suggest that rTNF-alpha can provoke acute pulmonary vascular endothelial injury in vivo as well as in vitro. PMID- 2925249 TI - Bacteriologic and serologic findings in experimental pyelonephritis caused by Ureaplasma urealyticum. AB - A challenge procedure based on reflux of Ureaplasma urealyticum to the rat kidney was used to examine the disease-causing potential of this species for the upper urinary tract. Renal infection was detected 8 days after challenge in 90 to 100% of animals exposed to 10(7) ureaplasmas but was not detected in animals exposed to fewer than 10(6) microorganisms. Viable microorganisms were recoverable from more than 60% of infected animals throughout a 24-week follow-up period of study. Animals with persistent infection exhibited a humoral response involving immunoglobulin M and immunoglobulin G antibody. These results show that U. urealyticum is capable of giving rise to chronic infection in the kidneys of rats following challenge via the ascending route. PMID- 2925248 TI - Bovine lactogenic immunity against cholera toxin-related enterotoxins and Vibrio cholerae outer membranes. AB - The newly parturient cow secretes large quantities of immunoglobulin G1, a relatively protease- and heat-resistant immunoglobulin, in its colostrum and milk. This study establishes the feasibility of producing protective colostral immunoglobulins by immunizing pregnant cows with cholera toxin (CT), a CT-related enterotoxin from Escherichia coli, and Vibrio cholerae outer membranes (OMs). The OMs were prepared from bacteria grown under iron-replete or iron-deficient (to simulate the in vivo environment) conditions. Immunoglobulins were purified from the colostrum of newly parturient control and immunized cows. The bovine anti-CT and anti-H-LT (CT-related heat-labile enterotoxin produced by diarrheogenic E. coli strains of human origin) antibodies were quantitated by enzyme-linked immunosorbent assays and by neutralization of toxin activity in both Y-1 adrenal cell and infant rabbit assays. The bovine anti-OM antibodies from both high-iron grown and low-iron-grown vibrios were assessed by bacterial agglutination and by Western blot (immunoblot) analysis of polyacrylamide gel electrophoresis of high iron-grown and low-iron-grown OMs. To test their protective effect, immunoglobulin preparations were administered orally in infant feeding formula to 6-day-old rabbits. Anti-CT and anti-OM immunoglobulins elicited statistically significant protection against diarrhea in infant rabbits challenged intraintestinally with virulent cholera vibrios. PMID- 2925250 TI - Bordetella parapertussis invasion of HeLa 229 cells and human respiratory epithelial cells in primary culture. AB - Bordetella parapertussis, a respiratory tract pathogen commonly regarded as noninvasive, was found to invade HeLa 229 cell monolayers. Following treatment of the monolayers with gentamicin, numbers of viable B. parapertussis recovered were comparable to those of invasive Salmonella and Shigella isolates. Invasion occurs through a cytochalasin-sensitive process which appears to be distinct from receptor-mediated endocytosis. Hyperimmune antisera raised against filaments hemagglutinin, a major adhesion of B. pertussis, did not inhibit invasion by B. parapertussis, suggesting that alternate adhesin(s) are required for invasion. In addition, B. parapertussis was found to invade human respiratory epithelial cells in primary culture, as demonstrated in ultrathin sections viewed by transmission electron microscopy. Although viable intracellular B. parapertussis persist within HeLa cells, they do not multiply there and the monolayers remain intact, suggesting a possible mechanism of carriage for these organisms. PMID- 2925251 TI - A Legionella pneumophila gene encoding a species-specific surface protein potentiates initiation of intracellular infection. AB - To investigate the pathogenesis of Legionnaires disease at a molecular level, we mutated by directed allelic exchange a gene encoding a Legionella pneumophila specific 24,000-dalton (Da) surface protein. Southern hybridization and immunoblot analyses demonstrated that the predicted DNA rearrangement occurred in L. pneumophila with a specific loss of 24-kDa antigen expression. Compared with its isogenic parent, the mutant was significantly impaired in its ability to infect transformed U937 cells, a human macrophagelike cell line; i.e., the bacterial inoculum of the mutant strain that was required to initiate infection of the macrophage monolayer was ca. 80-fold greater than that of the isogenic parent strain. The mutant strain regained full infectivity on reintroduction of a cloned 24-kDa protein gene, indicating that the reduced infectivity was due specifically to the mutation in that gene. Compared with the parent strain, the mutant strain was recovered at titers that were ca. 10-fold lower shortly after infection, but it exhibited a similar intracellular growth rate over the next 40 h, indicating that the mutant was defective in its ability to initiate macrophage infection rather than in its ability to replicate intracellularly. When opsonized, the mutant strain was still significantly less infectious than the parent strain, despite equivalent macrophage association, suggesting that the mutant was not merely missing a ligand for macrophage attachment. The mutant also exhibited reduced infectivity in explanted human alveolar macrophages, demonstrating the relevance of the U937 cell model for analyzing this mutant phenotype. These results represent the first identification of a cloned L. pneumophila gene that is necessary for optimal intracellular infection; we designate this gene mip, for macrophage infectivity potentiator. PMID- 2925253 TI - Characterization of a 29.4-kilodalton structural protein of Giardia lamblia and localization to the ventral disk [corrected]. AB - The amino acid sequence of a 29.4-kilodalton [corrected] structural protein located in the ventral disk and axostyle of Giardia lamblia was determined. Clone lambda M16 from a mung bean expression library in lambda gt11 expressed a fusion protein recognized by three different isolate-specific antisera and sera from G. lamblia-infected gerbils. One of the three EcoRI fragments (M16; 1.26 kilobases) encoded the recognized protein. Sequence analysis revealed a single open reading frame of 813 base pairs. Two areas showed conservation of the positions of some amino acids. The abundance of arginine, glutamic acid, and threonine was increased. Two potential alpha-helical regions were deduced in the regions of repeats. Antisera to the M16 fusion protein reacted specifically with internal components of the ventral disk and axostyle, as well as Giardia fractions enriched for ventral disk structural proteins. An identical protein was recognized in different isolates by anti-M16, and a single identical band was recognized in Southern blots using the M16 1.26-kilobase fragment as a probe. Therefore, the 29.4-kilodaltion [corrected] protein appears to be highly conserved compared with variant surface proteins. PMID- 2925252 TI - DNA sequence of mip, a Legionella pneumophila gene associated with macrophage infectivity. AB - In a previous study, a 24-kilodalton (kDa) protein surface antigen of Legionella pneumophila was cloned into Escherichia coli and found to be expressed on the host cell surface. Subsequently, a site-directed mutation in this gene (designated mip) in L. pneumophila was found to impair the capacity of this bacterium to initiate intracellular infection in human macrophages. The work presented here indicates that the antigenic gene product is distinct from the 24- to 29-kDa major outer membrane protein of L. pneumophila. In addition, the antigen was identified as a highly basic protein on two-dimensional nonequilibrium polyacrylamide gels and on two-dimensional monoclonal antibody immunoblots. When the DNA fragment encoding this protein was sequenced, a long open reading frame of 699 base pairs was identified within a region to which antigen expression was previously mapped. mip mRNA isolated from both L. pneumophila and transformed E. coli had the same 5' end, as determined by primer extension analysis, indicating that the same promoter sequences are used in both species. A likely factor-independent transcriptional terminator was found 20 residues downstream of the stop codon, suggesting that mip is encoded on a monocistronic message. The inferred polypeptide began with a possible 20- to 24 residue signal sequence, and, as predicted by two-dimensional electrophoresis, had a molecular weight of 24,868 and was a potent polycation with an estimated pI of 9.8. PMID- 2925254 TI - Interaction of Lyme disease spirochetes with cultured eucaryotic cells. AB - The association of the Lyme disease spirochete, Borrelia burgdorferi, with cultured human endothelial cells was investigated. Attachment was time and temperature dependent, with optimal adherence occurring after 4 h of incubation at 37 degrees C. Pretreatment of borreliae with heat, immune human serum, or monoclonal antibodies directed against outer surface protein B (OspB) reduced the attachment of organisms to host cell monolayers. These results suggest that the adherence of B. burgdorferi may be mediated, at least in part, by borrelial surface proteins. PMID- 2925255 TI - Effect of immunoglobulin M from normal human serum on Leishmania donovani promastigote agglutination, complement-mediated killing, and phagocytosis by human monocytes. AB - Serum from healthy, nonimmune humans contained immunoglobulin M (IgM) antibodies that agglutinated Leishmania donovani promastigotes, activated complement, and enhanced promastigote ingestion by human monocytes. The findings indicate that IgM antibodies have the capacity to affect the initial interaction of L. donovani promastigotes with human host defenses. PMID- 2925256 TI - Fenestrated capillaries in mice submesothelial mesenteric microvasculature. AB - This study demonstrates the existence of fenestrated capillaries in the microvascular bed of mice mesentery. The 26.6% incidence of fenestrated capillaries observed in this study is similar to that found in rabbit diaphragmatic peritoneum. Fenestral diameters are too large to be identified as the large pore of Pappenheimer's theory. They appear to be too frequent to become the predicted large pore. Peritoneal permeability should be analyzed on the basis that molecular transfer occurs through multiple ways. PMID- 2925258 TI - Glucose metabolism, lipidic pattern, apolipoprotein A and B during hemodialysis with cuprophan and hemodialysis-hemoperfusion. AB - We studied differences in the glucose metabolism, lipid pattern and apolipoprotein A and B after one month of combined hemodialysis-hemoperfusion (HD HP) in eight regular maintenance hemodialysis (HD) patients. After one month of HD-HP predialytic serum creatinine and phosphate were lower than during the preceding HD period; the lipidic pattern and apolipoproteins were unchanged. A single HD-HP session significantly reduced triglycerides; this does not occur during HD. Postdialytic changes of all other lipoprotein metabolism parameters are identical in the two techniques. As regards glucose metabolism, after one month of regular HD-HP treatment glycemic curves during the intravenous glucose tolerance test (IVGTT) were perfectly matched with those in HD. However, insulin production was lower, with a reduction of the insulin resistance index. Differences did not reach statistical significance. The Authors infer that activated charcoal, even though it achieves better blood purification in uremia, may be unable to remove specific substances which hamper some key enzyme activities of the carbohydrate and lipid metabolism. PMID- 2925257 TI - Different buffers for hemodiafiltration: a controlled study. AB - Hemodiafiltration (HDF) is usually performed using a dialytic solution (D) containing acetate (A) or bicarbonate (B) and a replacement fluid (RF) containing lactate (L). To clarify the role of buffers in HDF, 11 patients underwent different study periods, each three months long: bicarbonate hemodialysis (BHD = Baseline period); HDF with (A) in D and (L) in RF (first period of HDF); HDF with (A) in D and (B) in RF (second HDF); HDF with (B) in D and (L) in RF (third HDF); HDF with (B) in D and (B) in RF (fourth HDF = BHDF). HDF achieved: 1) an increase in dialytic efficiency (kt/V, 1.28), reducing the time-session (197 min); 2) an improvement in acid-base status (pre-dialytic values in BHDF: pH 7.36; pCO2 39.8 mmHg; HCO3- 21.8 mM/L); 3) better "dry weight" gain (reached in 92.8% of HDF and in 81% of BHD sessions); 4) a significant decrease, in dialytic side-effects (mainly during the third and fourth periods). On the whole, BHDF (HDF done using only bicarbonate buffer) represents an easy and safe technique, leading to better cardiovascular stability than BHD and HDF without bicarbonate buffer. PMID- 2925259 TI - Influence of different dialyzer membranes on plasma fibronectin levels in hemodialyzed patients. AB - Plasma fibronectin (FN) was assayed in 30 patients with chronic renal failure under conservative therapy, 60 uremic patients undergoing periodic hemodialysis, and 7 patients treated by hemofiltration. Plasma FN was significantly lower in uremic patients on conservative therapy and in those who received intermittent hemodialysis than in the control group. No difference was seen between mean FN concentrations using different dialyzer membranes. Nevertheless, plasma FN levels were significantly higher in subjects after intermittent hemofiltration. There was no evidence of activation of the coagulation system or of any correlation between FN and fibrinogen values. These findings suggest that conventional hemodialysis is not effective in improving the low levels of plasma FN found in uremic patients, whereas intermittent hemofiltration raises FN. These differences may be due to the fact that during hemofiltration, even when using the same dialyzer membranes as in conventional hemodialysis, some "substances" with high molecular weight that could block the synthesis of FN could be removed. PMID- 2925260 TI - Radionuclide assessment of the natural heart ejection fraction before and after LVAD implantation. AB - Complete pressure unloading of the ventricles can preserve ischemically damaged myocardium. Most clinical left heart assist device (LVAD) systems used after ischemic injury of the heart apply atrial cannulation which does not ensure pressure unloading. In order to assess the effect of the implantation of an intracorporeal LVAD on the function of the natural heart, we determined the ejection fraction (EF) in four male Holstein calves (90-105 kg) before and after insertion of a Cleveland Clinic pneumatic LVAD. A gated blood pool scan was obtained with a gamma camera after injection of 40 mCi Tc-labelled albumin. The animals were restrained in a sling to avoid movement artifacts. All animals showed a drop of 65 +/- 12% to 42 +/- 14% EF in the first postoperative (p.o.) week. Left ventricular output did not maintain sufficient blood pressure as assessed by pump-off tests. Systolic blood pressure dropped from 122 +/- 6.5 mm Hg to 81 +/- 6 mm Hg without pump support on the morning of the first p.o. day. Apical coring and possible restrained heart movement by the implanted LVAD may lead to impaired myocardial function that renders the individual LVAD dependent until adaptative corrections take place. PMID- 2925261 TI - The effect of colloid osmotic pressure on the survival of sheep following cardiac surgery. AB - The occurrence of late complications in implanted cardiac prosthetic valves has emphasized the need for the development of an animal model in which these complications are reproducible. Sheep constitute an excellent model for chronical and pathological studies of prosthetic devices. In our experience, survival of sheep following implantation of prosthetic valves is closely related to postoperative serum colloid osmotic pressure (C.O.P.). The normal range as measured in 28 healthy sheep was 16.67 +/- 0.55 mm Hg. A protocol was developed to maintain the colloid hydrostatic pressure gradient (C.H.P.G.) as close as possible to the normal physiological range, and to delay the extubation until the C.O.P. was within this range, and the C.H.P.G. greater than 7 mm Hg. Using the above protocol, a new tri-leaflet polyurethane valve was inserted into eight, five to seven month old sheep in place of the mitral and tricuspidal valves. One hour after terminating the extacorporeal circuit, the C.O.P. was measured at 13.10 +/- 0.96; but within five to six hours, it rose to 17.1 +/- 1.1. During the same period, the C.H.P.G. increased from 3.02 +/- 0.96 to 7.6 +/- 0.50 mm Hg. The postoperative period was uneventful, and all animals survived. We have thus concluded that the routine measurement and monitoring of C.O.P. constitutes a guide of great clinical importance. PMID- 2925262 TI - Modelling of plasma-separation through microporous membranes. AB - Available mathematical models of ultrafiltration have been used to predict changes in maximum plasma filtration rate with wall shear rate for given filters and blood properties. We have done many plasmapheresis experiments in vitro, using hollow-fiber filters (500-1000 cm2) and fresh bovine blood collected on ACD or heparin. The comparison between predicted and experimentally obtained filtration rates was good for models based on the concentration polarization theory and lift velocity theory. In other experiments with pulsatile inlet flow we found that plasma filtration rate increased by 20 to 50% compared to non pulsatile conditions. These results are in good agreement with the modified model of ultrafiltration incorporating pulsating flow. This paper presents relationships between plasma filtration velocity (steady and pulsating flow) and hemolysis limit as a function of wall shear rate and filter size. PMID- 2925263 TI - Effectiveness of erythrocytapheresis in idiopathic hemochromatosis. Report of 14 cases. AB - Thirteen men and one woman (mean age 48.8 yr +/- 6.9, range 36-63) with idiopathic hemochromatosis were treated by erythrocytapheresis. Iron depletion followed 9.60 months treatment (median 24), with 21-203 erythrocytaphereses (mean 93 +/- 61) and total iron removal of 4.2-40.6 g (mean 19 +/- 11.9). Trasferrin saturation decreased from 90 +/- 8.7% to 17 +/- 10.6% and serum ferritin from 3164 micrograms/L +/- 1488 to 60.5 micrograms/L +/- 77.5, and liver iron content normalized in all cases. Initial serum ferritin in the patients who were iron depleted at 18 months (50%, cumulative percentage) was significantly lower than in those still iron loaded at that time (2280 micrograms/L +/- 940 vs 4049 micrograms/L +/- 1444, p less than 0.02). Clinical improvement was noted in all cases with about a 30% decrease in insulin requirement in most diabetics. Thus erythrocytapheresis appears to be effective and safe in obtaining iron depletion in idiopathic hemochromatosis. PMID- 2925264 TI - A first screening for hemocompatibility of a universal support for selective and specific hemoperfusion. AB - A modified filmadsorber is presented, intended to be used for selective and specific hemoperfusion. It consists of a spirally wound cellulose nitrate film, onto which--after chemical activation with sodium periodate--albumin is bound, stabilized, sterilized and activated with glutaraldehyde. Various bioactive ligands containing amino groups can be coupled to this support. A subsequent treatment with dimethylamino borane stabilizes the bonds between cellulose nitrate, albumin, glutaraldehyde and ligand. Columns in which a second layer of albumin is bound to the support as a model for a bioactive ligand were first screened for hemocompatibility using rabbits. Leukocyte, thrombocyte and hematocrit behaviour during hemoperfusion showed that hemocompatibility of the support was good. PMID- 2925265 TI - Anti-neutrophil cytoplasmic antibodies (ANCA) in Wegener's granulomatosis. PMID- 2925266 TI - Time relationship between ambient temperature change and antigen stimulation on immune responses of mice. AB - We investigated the time relationship between ambient temperature change and antigen stimulation on immune responses to sheep red blood cells (SRBC) and polyvinylpyrrolidone (PVP) in mice. In the case of a shift from comfortable (25 degrees C) to cold (8 degrees C) temperatures, suppression in the number of splenic plaque-forming cells (PFC) took place mainly when the shift was done between 1 day before and 2 to 4 days after immunization. The suppression of the PVP response lasted for up to a maximum of 6 days when mice were transferred 1 day before immunization. In the case of a temperature shift from 25 degrees to 36.5 degrees C, the suppressive effect was found when the temperature shift was done between 4 days before and 2 days after immunization. The effect lasted longer than that of the temperature shift to cold, i.e., at least 9 days after the temperature shift. Blood corticosterone levels after the temperature shifts corresponded to changes in the immune responses: elevation of the blood corticosterone levels was observed for only the first 3 days after a temperature shift to 8 degrees C but for 10 days after a temperature shift to 36.5 degrees C during the period time of the experiment. These result suggested that blood corticosterone level contributes to the duration of the effects of temperature shifts on immune responses of mice. Furthermore, it appeared that the early stage of the immune response is more susceptible to temperature shifts than the later stage. To explain these results, the terms "effective period" in the course of physiological adaptation to changed ambient temperature and "susceptible period" in the course of the immune response, were proposed. PMID- 2925267 TI - Hydration and tissue solid content of the lean body on prolonged exposure to altitude. AB - Using densitometric, hydrometric and anthropometric techniques, body fat, tissue solids, water and mineral content were quantitatively measured on two groups each of 26 young and healthy Indian soldiers of mixed ethnic composition. The experimental group was exposed to 3500 m altitude for 2 years and the experiments were carried out after 48 h and 3 weeks rehabilitation in Delhi (300 m). The control group was never exposed to high altidues. Inspite of the experimental group being fed with superior rations at high altitude, this group showed significantly hyperhydrated lean body with reduced tissue solids in comparison to the control group which was fed with identical rations in Delhi. The calculated mean density of the fat free body had declined to 0.092 x 10(3) kg/m3. The 3 week stay at low altitude had little influence on body composition. Hyper-hydration, with reduced tissue solids, would cause reduction in the density of fat free body, and would thus interfere with the estimates of total body fat based on densitometric procedures alone. In the hyperhydrated state, Siri's formula overestimated fat by 22.8% of the true value. PMID- 2925268 TI - Environmental temperature and mortality from acute myocardial infarction. AB - Mortality from acute myocardial infarction (MI) over the 5 year period 1982-1987 in Brown County, Wisconsin, was analyzed to assess the relationship with environmental temperature. Deaths occurring on the day of and the day following a significant snowfall as well as deaths occurring in health care facilities were eliminated from consideration because the focus was upon temperature, not snowfall or events within a hospital. These criteria resulted in the inclusion of 1,802 days and 926 cases of acute MI. The mean temperature on the day of death was obtained from climatological data and were grouped into six categories covering a range of temperatures from less than -17.8 degrees C (0 degrees F) to 16.1 degrees C (61 degrees F). The number of deaths in each category was tabulated. The effect of temperature, sex, and age were analyzed by regression analysis. The results indicated a linear increase in mortality as mean daily temperature decreased over the temperature range. The inverse temperature effect was most pronounced in males over the age of 60. These results indicate that cold temperatures appear to be associated with an increased mortality from myocardial infarction. PMID- 2925269 TI - Pathologic prognostic factors for cutaneous malignant melanoma: the Western Canada Melanoma Study. AB - An analysis of data for histopathologic factors influencing survival was conducted on 798 cases of invasive cutaneous malignant melanoma. On univariate analysis, a number of factors influenced survival; however, when these factors were examined using a proportional-hazards model, sex and log of depth of penetration were the only factors governing survival. Moreover, these factors were only important in patients with lesions up to 4 mm in depth with no evidence of other disease. For patients with solitary lesions deeper than 4 mm, or patients with regional or distant disease, none of the factors examined in our study was of predictive value for survival assessment. PMID- 2925270 TI - Expression of transforming growth factor alpha messenger RNA in the normal and neoplastic gastro-intestinal tract. AB - The presence of TGF alpha mRNA has been reported previously to occur in primary colon cancers. We report the expression of the normal 4.5 kb TGF alpha transcript in the mucosa of the normal human gastro-intestinal tract from oesophagus through to colon. The highest levels of human TGF alpha mRNA occurred in the duodenum but significant levels were present in all of the mucosa. Similarly, in the rat gastro-intestinal tract, TGF alpha transcripts were detected in the lower gastro intestinal tract mucosa. The relative abundance of the TGF alpha mRNA appeared to decrease in distal regions of the gastro-intestinal tract. The level of the TGF alpha mRNA was similar in both the normal and the neoplastic colon tissue. Similarly, in 2 patients with carcinomas, the TGF alpha mRNA was expressed at similar levels in the tumour and in adjacent mucosa. Although TGF alpha mRNA is associated with transformed cells from the gastro-intestinal tract, the presence of this mRNA at equivalent concentrations in normal mucosa suggests that over production of TGF alpha is not an essential feature of carcinomas in the gastro intestinal tract. PMID- 2925271 TI - In vitro thermo-chemosensitivity screening of spontaneous human tumors: significant potentiation for cisplatin but not adriamycin. AB - The in vitro thermal enhancement of Adriamycin (ADR) and Cisplatin (CDDP) was investigated in 18 surgical biopsy specimens of human tumors cultured in the Adhesive Tumor Cell Culture System. Experimental conditions were adopted to simulate "therapeutic" trials: (a) temperature of 37.0 degrees C, 40.5 degrees C or 42.5 degrees C; (b) hyperthermic duration of 30, 60, or 120 min; and (c) 4 dose drug range normalized to human bone marrow toxicity. Drug concentrations that inhibited 90% of tumor growth (IC90) at 37.0 degrees C were compared to the IC90 at 40.5 degrees C and 42.5 degrees C, adjusted for the effect of heat alone. CDDP plus heat was a better combination than ADR plus heat, regardless of the temperature and the exposure duration: significant synergism (p less than 0.001) occurred in 37% of heat-CDDP combinations, as compared with 15% of heat-ADR combinations, and antagonism was significantly lower (p less than 0.001) for heat CDDP than for heat-ADR (4.4% versus 21% of combinations, respectively). Within the CDDP group, higher temperature and longer heat exposure resulted in an increased incidence of chemosensitivity. No specific pattern of synergism was evident within the ADR group, but a trend toward a higher incidence of antagonistic effects with increasing hyperthermic duration was observed. PMID- 2925272 TI - Pancreatic cancer, alcohol, diabetes mellitus and gall-bladder disease. AB - A case-control study comprising 216 cases of pancreatic cancer and 279 controls was conducted to investigate the relationship of pancreatic cancer with certain chronic medical conditions and with the consumption of tea, coffee and alcoholic beverages. Significant positive associations with pre-existing diabetes mellitus and gall-bladder disease were observed and there was weak evidence of association with liver disease. The relative risks for diabetes mellitus and gallstones diagnosed at least one year previously were 4.1 (p = 0.005) and 2.8 (p = 0.01) respectively. Cases drank significantly more beer than controls (p = 0.005) and there was evidence of a positive trend in risk with total alcohol consumption. Smoking was a clear risk factor, but cases and controls were very similar with respect to tea and coffee drinking habits. PMID- 2925273 TI - Tissue-specific expression of a constitutional 3;6 translocation: development of multiple bilateral renal-cell carcinomas. AB - We describe a German family carrying a constitutional translocation (3;6) (p13;q25.1) in 3 consecutive generations. The only member of the family over 50 years of age and carrying the translocation developed multiple bilateral renal cell carcinomas. We performed chromosome analysis of 4 out of 5 primary tumours, which were characterized by different clonal karyotypes. The constitutionally translocated 3p13-pter segment was lost with or without the receptor chromosome 6 in each tumour. Additional karyotypic changes were trisomy 5, 7 and 18, monosomy 14 and 21, and loss of the Y chromosome, all karyotype changes occurring frequently in sporadic non-papillary RCCs. This case is discussed with regard to the possible role of suppressor gene inactivation by constitutional translocation in the development of familial renal cancers. PMID- 2925274 TI - Amplification of c-ras-Ki oncogene in human ovarian tumours. AB - Amplification of the c-ras-Ki oncogene has been the most consistent finding reported in studies on oncogene activation in ovarian cancer, but for the most part the studies have been small and the results conflicting. In order to determine whether amplification occurred de novo in primary tumours or was associated with tumour progression and metastasis, 81 tumour samples from different sites in 26 patients with ovarian tumours and 7 xenografted ovarian tumour cell lines were assayed. Amplification of c-ras-Ki occurred infrequently and was apparent in a single metastatic site in a patient with poorly differentiated serous cystadenocarcinoma of the ovary. Ten-fold amplification of the c-ras-Ki oncogene was also evident in a benign ovarian fibroma. Amplification of the c-ras-Ki oncogene is rare in ovarian tumours and does not appear to play a fundamental role in tumor development or progression. PMID- 2925275 TI - Use of the Membrane Invasion Culture System (MICS) as a screen for anti-invasive agents. AB - The Membrane Invasion Culture System (MICS) assay was adapted for relatively rapid screening of compounds and used to identify anti-invasive drugs that inhibit human and murine tumor cell migration through a reconstituted basement membrane in vitro. Cell lines demonstrating low and high invasive and metastatic potentials were tested with all compounds for tumoricidal effects prior to evaluation in MICS at non-cytotoxic doses. The effect on invasive potential in the MICS assay was determined in 3 categories: (1) 48 hr drug pre-treatment prior to seeding in the MICS (exceptions: 90 min pre-treatment with pertussis toxin and, for some studies, continuous exposure for 2-7 days); (2) peptide or prostaglandins 2 hr after seeding and attachment to the membranes in MICS followed by continuous exposure; and (3) cells receiving neither drug nor peptide treatment and serving as controls in each MICS chamber. Since invasion involves cellular motility and deformability, some cytoskeleton disrupting agents were selected. Of these, vincristine, colcemid and colchicine inhibited invasion but taxol did not. Pre-treatment with cAMP agonists produced conflicting results: dibutyryl cAMP and 8-(4-chloro-phenylthio) cAMP resulted in 50% and 38% reduction in invasion, respectively, whereas 8-bromo cAMP stimulated invasive potential by 30%. Forskolin and cholera toxin both significantly reduced invasiveness. Pre treatment with 5-azacytidine and araC, to consider the role of methylation and proliferations decreased invasive ability. Anti-metastatic drugs such as gamma interferon and razoxane inhibited invasive potential but to varying degrees. Treatment of cells with prostaglandins E2, F2 alpha, A2, and D2 were ineffectual; however, indomethacin mildly inhibits invasion (less than 30%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2925276 TI - Effects of propranolol and cimetidine on cysteamine inhibition of gastric carcinogenesis induced in Wistar rats by N-methyl-N'-nitro-N-nitrosoguanidine. AB - The effects of propranolol and cimetidine on inhibition by cysteamine (2 aminoethanethiol hydrochloride) of gastric carcinogenesis induced by N-methyl-N' nitro-N-nitrosoguanidine (MNNG) and on gastric acid secretion, serum gastrin level, and labelling index of the gastric mucosa were investigated in inbred Wistar rats. Rats received alternate-day injections of cysteamine (25 mg/kg body weight) with or without propranolol (dl-propranolol hydrochloride) (2 mg/kg bw) or cimetidine (50 mg/kg bw) in depot form after 25 weeks of oral treatment with MNNG. Prolonged administration of cysteamine significantly reduced the incidence of adenocarcinoma of the glandular stomach. A combination of cysteamine and propranolol significantly accelerated the inhibitory effect of cysteamine on gastric carcinogenesis. However, with concomitant administration of cysteamine and cimetidine, the incidence of adenocarcinoma was slightly but not significantly increased as compared to that after treatment with cysteamine alone. Administration of cysteamine caused a significant increase in gastric acid secretion and serum gastrin level, and a significant decrease in the labelling index of the antral mucosa. A combination of cysteamine and propranolol significantly increased gastric acid secretion by cysteamine alone and significantly decreased the labelling index of the antral mucosa. With this treatment, the serum gastrin level was significantly higher than the basal level, but the stimulated serum gastrin level was significantly lower than observed that after administration of cysteamine alone. In contrast, concomitant administration of cysteamine and cimetidine caused a significant decrease in gastric acid secretion and significant increase in the serum gastrin level as compared to the levels seen after treatment with cysteamine alone, but had no influence on the labelling index of the antral mucosa. These findings indicate that hypersecretion of acid, but not hypergastrinemia associated with hyposecretion of acid or achlorhydria, exerts a protective effect against gastric carcinogenesis, and that this effect may be related to its activity in decreasing proliferation of the antral mucosa. PMID- 2925277 TI - Over-expression of MDR1 gene with no DNA amplification in a multiple-drug resistant human ovarian carcinoma cell line. AB - Human ovarian adenocarcinoma cells IGROV1 were induced to become resistant in vitro to Vincristine (VCR) by continuous and discontinuous stepwise exposure to the drug. Both sublines exhibited similar indexes of resistance (approx. 800). The acquisition of VCR resistance was associated with changes of morphology and with cross-resistance to Adriamycin, VP16 and actinomycin D. Addition of verapamil enhanced sensitivity of resistant cells to VCR. This multi-drug resistant (MDR) phenotype was associated with high levels of human MDR1 gene transcripts (25- to 100-fold). In contrast to other reports, no significant amplification of the locus could be observed. Reactivity with MRK16, a monoclonal antibody (MAb) directed against the MDR 170 kDa protein, was found to be related to the level of MDR1 transcription. In addition, both OV1/VCR sublines exhibited a marked loss of tumorigenicity. Besides the chromosomal markers of OV1/p, the two resistant sublines revealed a common cytogenetic rearrangement: a deletion of the short arm of one chromosome 11: del(11)(p12). We suggest that the acquisition of this marker might be associated with the non-tumorigenic phenotype of OV1/VCR resistant sublines. PMID- 2925278 TI - Circumvention of adriamycin resistance by dipyridamole analogues: a structure activity relationship study. AB - Dipyridamole restores sensitivity to Adriamycin (ADR) in drug-resistant cells. In an effort to elucidate the relationship between activity and chemical structure of dipyridamole, the ability to enhance the growth inhibitory effect of ADR, in multidrug-resistant (MDR) P388 murine leukemia cells, was determined for 43 derivatives and related compounds. Since both substituted pyrimidopyrimidines and pteridines enhanced the growth-inhibitory effect of ADR in drug resistant cells, the core skeleton may not be directly involved and rather serve as a carrier for the substituents connected with this activity. The exact positions of the active substituents on the core skeleton did not seem to be critical for exertion of the activity. Activity was dependent on the presence of 3 tertiary amine groups. However, not all tertiary amines showed the same potency which might be related to the degree of basicity and/or the spatial structure of these groups. The most active derivatives carried piperidine and pyrrolidine groups while derivatives with thiomorpholine, 3-hydroxypiperidine or dimethylamine groups had low activity. Activity was also dependent on the presence of a substituent with partial electronegative charges as found in a diethanolamine group. However, this function could be carried out, with even higher efficiency, by a substituent containing 6 pi electrons. PMID- 2925279 TI - Carcinogenicity of iron in conjunction with a chlorinated environmental chemical, hexachlorobenzene, in C57BL/10ScSn mice. AB - Pre-loading of C57BL/10ScSn mice with iron greatly sensitizes them to the induction of hepatic porphyria caused by hexachlorobenzene (HCB) (Smith and Francis, 1983). HCB will also cause liver tumours in experimental animals. Elevated liver iron stores are implicated in the development of some human liver cancers. To determine whether iron overload will potentiate the hepatocarcinogenicity of HCB, male C57BL/10ScSn mice received a single dose of iron-dextran complex or the dextran carrier and were then fed HCB in the diet (0.01%) for up to 18 months. A very clear potentiation by iron of liver tumour incidence occurred. Of the mice which received HCB, but no iron, for 12 months a low incidence of liver hyperplastic nodules was observed, whereas preadministration of iron increased the incidence. After 18 months, all surviving mice initially given iron followed by HCB developed advanced hepatic nodules and 90% had hepatocellular carcinomas. No tumours were seen in animals that only received HCB. Nodules were not seen in iron-dosed mice receiving control diet, but another novel observation was that these animals developed porphyria by 6 months. Although iron enhanced tumour formation in the presence of HCB, the foci, nodules and carcinomas formed all excluded iron. Preliminary studies with the DBA/2 strain suggested that these mice were considerably less susceptible to potentiation by iron. PMID- 2925280 TI - The intracellular association of B700 and B50 murine melanoma antigens and their role in tumor rejection. AB - B700 and B50 are melanoma-specific antigens originally isolated from B16 murine melanoma. B700, which elicits a strong tumor rejection response, is present on all murine melanomas tested to date. We now demonstrate the presence of B50 in the other murine melanomas and find that the 2 molecules are non-covalently complexed with each other within the cells. We also show that hosts immunized with intact, irradiated melanoma cells produce antibodies that specifically recognize the B700 and B50 tumor antigens. These results suggest that B50 may also participate in the host response to melanoma growth. PMID- 2925281 TI - Effect of erythromycin and tumour necrosis factor on the drug resistance of multidrug-resistant cells: reversal of drug resistance by erythromycin. AB - WEHI 164 murine fibrosarcoma cells were rendered multidrug-resistant (MDR) by culture in the presence of actinomycin D. In addition to resistance to actinomycin D, the cells acquired resistance to doxorubicin, mitomycin, vincristine and cycloheximide. The fact that development of resistance to one type of lipophilic chemotherapeutic drug also results in resistance to other structurally unrelated lipophilic drugs suggests that non-toxic lipophilic agents may interfere with drug resistance by saturating the pathway by which MDR-cells inhibit drug cytotoxicity. We show that the antibiotic erythromycin significantly reverses the resistance of MDR WEHI 164 cells to doxorubicin and actinomycin D. In addition to cross-resistance to chemotherapeutic drugs, 3 out of 4 actinomycin D-resistant WEHI 164 cell lines also showed higher resistance to tumour necrosis factor (TNF) than the parental WEHI 164 cells. However, whereas verapamil, a calcium antagonist known to reverse multidrug-resistance, rendered resistant cells more sensitive to chemotherapeutic drugs, it protected the cells from killing by TNF, suggesting that drug resistance and TNF resistance may not be directly connected. A synergistic cytotoxic effect of TNF and actinomycin D was obtained on both the parental and the MDR cells. However, higher concentrations of TNF and actinomycin D were required to obtain a cytotoxic effect in the MDR cells, reflecting actinomycin D and TNF resistance in these cells. PMID- 2925282 TI - Angiographic abnormalities of the morphologically left ventricle in the presence of Ebstein's malformation. AB - Cineangiography of the morphologically left ventricle was performed in 10 patients with Ebstein's malformation. The angiographic findings included left ventricular contour abnormalities (8), mitral valve prolapse (7) and global hypokinesia (5). Left ventricular abnormalities were present whether the left ventricle was normally placed or in mirror-image position in congenitally corrected transposition. Abnormalities of the morphologically left ventricle in Ebstein's malformation have received little attention in the past. Frequent occurrence of these abnormalities should make careful evaluation of the morphologically left ventricle mandatory in all patients with Ebstein's malformation. PMID- 2925283 TI - Dilated cardiomyopathy with regional myocardial hypoperfusion in Becker's muscular dystrophy. AB - We describe two cases of Becker's muscular dystrophy, both of which presented with a dilated cardiomyopathy with alterations of myocardial perfusion and hypokinesia in the anteroseptal and apical ventricular walls. To the best of our knowledge, only one case with similar cardiologic characteristics has been reported previously. Myocardial involvement in this disease is comparable to that found in the Duchenne form of dystrophy. The possible mechanisms underscoring its induction are discussed. PMID- 2925284 TI - Diagnosis of pulmonary venous obstruction by Doppler echocardiography. AB - A 1 1/2-year-old female patient with atrial and ventricular septal defects and severe pulmonary arterial hypertension was found to have discrete stenosis of left upper and middle lobe pulmonary veins. The diagnosis was made by cross sectional and Doppler echocardiography. The findings were confirmed at cardiac catheterization and operation. Pressure gradients across the pulmonary vein stenosis as obtained by Doppler echocardiography correlated well with those measured at cardiac catheterization. PMID- 2925285 TI - Changes in regional myocardial cross-sectional area during brief coronary occlusion and reperfusion in conscious dogs. AB - The effect of a brief period of coronary occlusion on a regional myocardial cross sectional area was studied in 6 conscious dogs. Subendocardial segment length and wall thickness were continuously measured with a sonomicrometer in the central ischemic area perfused by the left circumflex coronary artery during a 2-min circumflex occlusion and subsequent reperfusion. Measurements were repeated before and after collateral development induced by 180 +/- 30 (SEM) 2-min circumflex occlusions (20 +/- 3 days). In order to evaluate the changes in regional myocardial volume, end-diastolic regional cross-sectional area was calculated as a product of end-diastolic segment length and wall thickness. Before collateral development, end-diastolic regional cross-sectional area transiently decreased 1.4 +/- 0.6% (NS) at 10 sec following sudden coronary occlusion, thereafter gradually increased to 3.7 +/- 1.0% (P less than 0.05) at the end of a 2-min occlusion. At 10 sec of reperfusion, end-diastolic regional cross-sectional area further increased to 7.0 +/- 1.1% (P less than 0.05) probably due to increased intravascular volume. Increase in end-diastolic regional cross-sectional area was still 2.5 +/- 0.6% (NS) at 3 min after the release of occlusion. After collateral development, the changes in end-diastolic regional cross-sectional area were 0.1 +/- 0.1% (NS), 0.4 +/- 0.3% (NS), 1.0 +/- 0.6% (NS) and 0.2 +/- 0.4% (NS), respectively. Thus, a significant increase in the regional myocardial cross-sectional area occurs during a brief period of coronary occlusion and reperfusion. PMID- 2925286 TI - Changes in isovolumic segment shortening following acute coronary occlusion: disproportionate effects of anterior versus posterior ischemia. AB - We evaluated the changes in left ventricular pressure and isovolumic segment shortening in both the ischemic and nonischemic areas following acute coronary occlusion in 12 conscious dogs instrumented for the measurement of subendocardial segment lengths perfused by the left circumflex coronary artery and left anterior descending coronary artery, and left ventricular pressure. An externally inflatable pneumatic occluder was placed around the left circumflex coronary artery. In 6 dogs, another occluder was installed around the proximal left anterior descending coronary artery. Under the resting conditions, the isovolumic segment shortening in the areas supplied by the left anterior descending coronary artery and the left circumflex coronary artery were 2.1 +/- 0.5% (SE) and -0.1 +/ 0.5% (P less than 0.01; versus values in the area of the left anterior descending coronary artery), respectively. During a 1-min occlusion of the left circumflex coronary artery, the isovolumic shortening in the anterior segment increased to 3.8 +/- 0.5% (P less than 0.001; versus values in the basal state), while the posterior segment produced isovolumic elongation (-2.2 +/- 0.5%, P less than 0.001; versus values in the basal state). By contrast, during a 1-min occlusion of the left anterior descending coronary artery, the extent of isovolumic bulge in the anterior segment and the augmentation in the isovolumic shortening in the posterior segment was less prominent compared with the occlusion of the left circumflex coronary artery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2925288 TI - Is the sinus node visible grossly? A histological study of normal hearts. AB - The sinus node is said to be occasionally visible in the human heart, while some have denied this visibility. This histological study of the normal sinus node was made on 11 adults and 10 infants. The node was always located subepicardially along the terminal groove at the junction of the superior caval vein and the right atrium. When no fatty infiltration (all infants and 2 adults) or minimal fatty tissue (2 adults) was found over the epicardial side of the node, it was not visible grossly. When fatty infiltration was obvious, then the node could be identified grossly as a yellowish spindle-shaped structure along the terminal groove. This arrangement was observed in 7 adults. The majority of nodes were in lateral position, but the so-called horseshoe arrangement was seen in 2 infants and 2 adults. The artery to the sinus artery was located centrally or eccentrically in the majority of cases, but the artery ramified through the nodal substance in 1 infant and 4 adults. We conclude that the node is not visible grossly in either the infant hearts or in those adult hearts without fatty infiltration. The whole cephalic part of the terminal groove should be carefully avoided to be sure of preventing the injury to the node during cardiac surgery. PMID- 2925287 TI - Cellular electrophysiologic effects of dexamethasone sodium phosphate: implications for cardiac stimulation with steroid-eluting electrodes. AB - Impregnation of implantable cardiac pacemaker electrodes with dexamethasone sodium phosphate dexamethasone) has been associated with reduced energy requirements for both atrial and ventricular stimulation. To determine whether cardiac cellular electrophysiologic effects of dexamethasone could in part account for lower stimulation thresholds, conventional microelectrode recording and stimulation techniques were used to assess both the immediate (acute) effects of dexamethasone (10(-6) and 10(-4) M) in superfused isolated rabbit right atrial and right ventricular preparations, and chronic effects in rabbit right ventricular tissue following 2 weeks of either daily parenteral dexamethasone (5 mg/kg, plasma concentration approximately 1 to 5 x 10(-5) M) or saline placebo injections. In acute superfusion studies, dexamethasone resulted in a concentration dependent prolongation of spontaneous right atrial cycle length, but did not significantly affect right atrial transmembrane action potential characteristics or refractoriness. However, acute dexamethasone superfusion tended to increase right ventricular resting membrane potential and diminish stimulation threshold. On the other hand, compared to findings in saline-injected control rabbits, chronic dexamethasone injection had little effect on right ventricular stimulation threshold transmembrane action potential characteristics, or right ventricular refractoriness. Thus, the acute direct electrophysiologic effects of high-dose dexamethasone are compatible with the early reduction of cardiac stimulation thresholds associated with dexamethasone impregnated pacing electrodes. On the other hand, electrophysiologic findings in the presence of chronic dexamethasone exposure do not fully account for long-term reduction of stimulation energy requirements. PMID- 2925289 TI - Coexistent cardiac tumours and malformations of the heart. AB - Cardiac tumours and anatomical malformations of the heart may produce similar clinical signs and symptoms. The coexistence of these two abnormalities complicates diagnosis and probably adversely affects prognosis. We present a review of four cases of this rare combination. In the first case, Ebstein's malformation was present in a child with tuberous sclerosis and cardiac rhabdomyomata. Right ventricular rhabdomyomata were associated with a hypoplastic tricuspid valve in the second case. In the third case, cardiac myxomas were detected in a child with a double-chambered right ventricle. The fourth case was a child with a fibroma of the right ventricle with pulmonary atresia. We propose that, in some circumstances, a space-occupying lesion may be associated with, or possibly induce, a malformation within the developing heart. PMID- 2925290 TI - Cardiovascular cavities cast in silicone rubber as an adjunct to post-mortem examination of the heart. AB - We used silicone rubber as a material for making post-mortem casts of cavities in 21 human hearts, 16 of them congenitally malformed, 13 after surgical reconstruction (Fontan and Norwood procedures) and 4 after reconstruction had been performed posts mortem for study purposes. The organs were either fresh, or had been perfusion fixed with formalin prior to casting. When suitable silicone rubber and catalyst were used, we found that casts allowed a very clear view of chamber morphology, and, where surgery had been performed, of any vascular constriction or distortion. We made casts of the aortic sinus and coronary arteries in 3 adult hearts, demonstrating the location and extent of indentation due to atheromatous deposits. The resilience and non-adhesiveness of the silicone rubber allowed casts to be extracted without recourse to corrosion. The surrounding tissues, with the exception of trapped trabeculations and valve structures, were then available for conventional pathological examination. We propose that the relatively simple technique has important applications, not practicable using earlier casting materials, for the study of cardiovascular morphology, and for post-mortem evaluation of stenosed or surgically reconstructed vessels. PMID- 2925291 TI - Changes in body attitude as a function of posthypnotic suggestions. AB - This study hypothesized that highly hypnotizable Ss who remained amnesic for posthypnotic suggestions to improve body attitude would show greater changes than Ss who were not amnesic. Ss given simulating instructions were used as a comparison group to assess experimental demands. 48 females were screened with the Harvard Group Scale of Hypnotic Susceptibility, Form A (Shor & E. Orne, 1962) and assigned to one of 4 conditions: (a) high hypnotizable with amnesia suggestions, (b) high hypnotizable without suggested amnesia, (c) low hypnotizable simulators with amnesia, and (d) low hypnotizable simulators without suggested amnesia. A fifth group was formed of those high hypnotizable Ss who remembered the suggestion despite instructions to the contrary. The Body Attitude Scale (Kurtz, 1966) was administered prior to and 3 days after the experimental suggestions. Results generally demonstrated that high hypnotizable amnesic Ss manifested the greatest attitudinal and phenomenological changes as a result of the posthypnotic suggestion, although conclusions were tempered by performance of simulating Ss. The implications for hypnosis research and clinical practice are discussed. PMID- 2925292 TI - The effects of hypnosis upon cognitive responses to persuasive communication. AB - Several writers have suggested that hypnotic responsiveness is directly related to the content of S's covert self-statements. To test this notion, low and high hypnotizable Ss in either hypnosis or waking conditions were exposed to a recorded message advocating that college seniors be required to pass a comprehensive exam in order to graduate. Following message presentation, Ss listed all of the thoughts which occurred to them while listening to the message; these thoughts were later coded as counterarguments, favorable thoughts, or neutral thoughts. Hypnotized Ss generated significantly fewer counterarguments and agreed more with the message than waking Ss. In addition, high hypnotizable Ss (in both waking and hypnosis conditions) produced significantly more favorable thoughts and agreed more with the message than low hypnotizable Ss. Results, therefore, provided a demonstration of the differential impact of context (induction) and trait (hypnotizability level) upon different cognitive phenomena. Implications for the occurrence of hypersuggestible behavior are discussed. PMID- 2925293 TI - Music absorption and hypnotizability. AB - The present study investigated differences between high (N = 15), medium (N = 20), and low (N = 16) hypnotizable Ss' involvement in imaginative versus nonimaginative music. Ss were first screened for hypnotizability with the Harvard Group Scale of Hypnotic Susceptibility, Form A (Shor & E. Orne, 1962). In a second session presented as a study of music appreciation, Ss listened to classical music of high and low rated music imaginativeness. Ss' involvement was indexed by absorption, imagery elaboration reported in open-ended essays, and reaction time to a pure tone. High hypnotizable Ss reported more absorption than low hypnotizable Ss, regardless of the imaginativeness level of the music. Ss reported more imagery elaboration in the imaginative than in the low imaginative passages. High hypnotizable Ss tended to differ in their imagery elaboration in response to the imaginative passages but not in response to the nonimaginative passages. Reaction time results were nonsignificant. No sex differences were found. Medium hypnotizable Ss were indistinguishable from both high and low hypnotizable Ss. The findings are generally compatible with J. R. Hilgard's (1970, 1974) construct of imaginative involvement. PMID- 2925294 TI - Effects of hypnotic analgesia and hypnotizability on experimental ischemic pain. AB - Mechanisms of hypnotic analgesia are still poorly understood and conflicting data are reported regarding the underlying neurochemical correlates. The present study was designed to investigate the effects of hypnotically induced analgesia and hypnotizability on experimental ischemic pain, taking into account pain and distress tolerance as well as the neurochemical correlates. 11 high hypnotizable Ss and 10 low hypnotizable Ss, as determined by scores on the Stanford Hypnotic Susceptibility Scale, Form C (Weitzenhoffer & E. R. Hilgard, 1962), were administered an ischemic pain test in both waking and hypnotic conditions. The following variables were measured: (a) pain and distress tolerance, (b) anxiety levels, and (c) plasma concentrations of beta-endorphin and adrenocorticotropic hormone (ACTH). Results confirmed significant increases of pain and distress tolerance during hypnosis as compared to the waking state, with positive correlations between pain and distress relief and hypnotizability. Moreover, a hypnotically induced dissociation between the sensory-discriminative and the affective-motivational dimensions of pain experience was found, but only in high hypnotizable Ss. Hypnotic analgesia was unrelated to anxiety reduction and was not mediated either by endorphins or by ACTH. PMID- 2925295 TI - Hypnosis in the management of symptoms in a young girl with malignant astrocytoma: a challenge to the therapist. AB - This paper presents the case of a 6.5-year-old girl with malignant astrocytoma of the left brain hemisphere. During the course of her chemotherapy treatment, severe vomiting developed to the degree that on several occasions she became dehydrated. Discontinuation of chemotherapy was being considered when she was referred for hypnotherapy. Despite severe neurological impairments which excluded many traditional techniques, hypnosis was successful in eliminating emesis. Hypnosis was also utilized to decrease pain and to improve sleep patterns. Drawings are presented to help show how this child resolved anxiety associated with treatment and fears surrounding the knowledge of her impending death. PMID- 2925296 TI - The rediscovery of the National Health Program by the Democratic Party of the United States: a chronicle of the Jesse Jackson 1988 campaign. AB - This report chronicles the major developments in the Jesse Jackson 1988 Campaign and their consequences for the establishment of a national health program in the United States. It describes the characteristics of the Jackson 1988 Campaign, and the set of events that led to the rediscovery of the national health program by the Democratic Party of the United States. PMID- 2925297 TI - Structural barriers to change in the workplace. AB - This article introduces the second series of articles in the Special Section on work organization and health. Empirical research has indicated that increased control--at both an individual and collective level--is a fundamental component of preventive psychosocial interventions aimed at ameliorating the impact of occupational stress-related disorders. However, practical intervention activities oriented toward enhancing levels of worker control have met structural obstacles at the level of the state, the occupational sector, and the workplace. The articles in this issue address these obstacles and suggest strategies for overcoming them from historical sociological, occupational health policy, and action research orientations. PMID- 2925298 TI - Action research on occupational stress: involving workers as researchers. AB - In this article we describe the rationale, design, and selected results of a longitudinal action research project conducted in a component-parts manufacturing plant. This project is aimed at reducing occupational stress and strengthening psychosocial factors (i.e., social support and participation in and influence over decision-making) that may mediate the negative effects of stress on health and quality of worklife. A discussion of the gaps and weaknesses in the existing research and intervention literature on work stress and health is provided, followed by an overview of the theoretical and empirical foundations of the present study. The design of this research addresses previous limitations in three major ways: (1) the project has been implemented within an action research framework that has the potential to enhance both the quality, relevance, and utilization of research findings and the adoption, diffusion, and impact of planned interventions; (2) it combines research and intervention in a single longitudinal study providing data that allow for stronger causal inferences than cross-sectional research, while also ensuring that research findings guide the design and evaluation of the interventions; and (3) it employs multiple methods of research and intervention that enhances the comprehensiveness and validity of the project. We explicate each of these aspects of the design, show how the design has effectively been put in operation, provide evidence of ways in which these features have improved the project over conventional approaches, and address limitations in terms of effectiveness and efficiency. PMID- 2925299 TI - The implications of work organization for occupational health policy: the case of Canada. AB - This article examines occupational health and safety developments in Canada during the decade of the 1970s when most government jurisdictions replaced former factory Acts with new health and safety legislation recognizing the right of workers to be involved in work environment matters. During the latter part of the 1970s, health and safety "activists" and trade unionists began to perceive the need for a wider conception of occupational health and safety. Canadian reformers were influenced by Scandinavian developments, especially the research of Dr. Bertil Gardell and his associates. Unfortunately, during the late 1970s Canada experienced a recession and a political shift to conservatism. Consequently, during the 1980s there have been no meaningful workplace health and safety reforms. Further, the article suggests that there is strong resistance by management and government to extension of worker rights in occupational health and safety. All major political parties ground their work environment policies in utilitarian concepts that trade worker health and safety for economic considerations. The author, therefore, argues for the development of an "ethics of the work environment" based upon egalitarian principles, and the transformation of the primary work group into a community of workers who can shape the character of their work environment. Ideally, the relationship between the major "actors" in our industrial relations system ought to be based on obligation instead of the present language of worker protest based on rights. Nonetheless, there is a need to extend and deepen worker rights in the workplace. Finally, the author argues that the appropriate relationship in industry to reflect a democratic work environment is "partnership"--the coming together of the primary work groups as equals. PMID- 2925300 TI - The feminization of poverty: myth or reality? AB - The feminization of poverty is a widely discussed concept in the mass media, and in academic circles, which captures the following facts: there are more poor women than poor men, and women are more likely to fall into poverty because of gender-related factors. In this article, I examine the concept's empirical basis and theoretical significance. The data show that poverty among men increased faster than poverty among women during the 1980-81 recession. While the sex composition of the poverty population has remained relatively unchanged since 1966, its age composition has changed: poverty has increased substantially among working men and women aged 18 to 44. Also, the higher proportion of women in the poverty population cannot be considered simply an effect of male privilege; on the contrary, it may be partially accounted for by higher mortality rates among working-class men. Theoretically, I argue that the meaning of these trends cannot be established using only age and sex categories of analysis. The trends document the progressive immiseration of the working class. Younger workers of both sexes today are worse off than older workers. A discussion of poverty purely in terms of the age, sex, or racial/ethnic composition of the poverty population hides the roots of poverty in the mode of production and succeeds in obfuscating the issues, fueling conflict between men and women, young and old, and white and nonwhite. Only by taking into account the class relations that structure people's life chances is it possible to understand the significance of present trends. PMID- 2925301 TI - Professional ideology and the construction of western psychiatry in Southeast Asia. AB - This article provides a critical examination of the professional ideology associated with the expansion of psychiatric treatment in the ASEAN countries of Southeast Asia. Four components of professional ideology are identified: appeal to "modernization"; medicalization of social problems; integration of psychiatry with primary health care; and panhuman uniformity of mental illness. However, the adoption of psychiatric technology has been a significant factor in the erosion of indigenous systems of social and psychological support since the colonial period. Contemporary psychiatric practices are also shown to exacerbate social inequalities, enhance state control of the populace, and continue to operate without adequate validation of diagnoses and treatments. PMID- 2925302 TI - The development of health care policies in Trinidad and Tobago: autonomy or domination? AB - This article is part of a study that described and analyzed the development of nursing education in Trinidad and Tobago from self-government in 1956 to 1986, with special emphasis on the forces that helped to shape the society from colonial times, and consequently, nursing education. Adaptation and application of major concepts from theories of underdevelopment and development and colonialism formed the basis of the study's theoretical framework. The article focuses on the impact of the metropolitan countries on the development of health care policies. Because of the nation's historical legacy of colonialism and its current linkages with the United States and Canada, a major area fundamental to the analysis was to determine whether those two countries had superseded traditional British influences in determining health care policies. This raised the issue of whether or not health care policies could be autonomously developed to meet the needs of the people. PMID- 2925303 TI - Accommodating rapid growth in physician supply: lessons from Israel, warnings for Canada. AB - Most developing countries find themselves grappling with the implications of rapid growth in physician supply. The purpose of this article is to search for lessons or warnings for Canada (and, ultimately, elsewhere) in the manner in which Israel has chosen to accommodate its huge supply of physicians. Under extremely conservative assumptions about immigration, and assuming rates of domestic training of physicians at levels somewhat lower than at present, Canada's physician supply will continue to grow at rates in excess of general population growth for at least the next 45 years. In this article we describe the Israeli health care system from a perspective of identifying the consequences of accommodating a physician supply about 50 percent higher than that in Canada. A number of key "accommodation attributes" (low physician incomes, restricted access to hospitals for general practitioners, intramedical-professional conflicts over income and authority, a flourishing black market) are argued to be more than simply products of a unique cultural and political system, but also symptoms of a system vastly oversupplied with physicians. Early signs in Canada of similar "products" of a growing physician supply are noted. While a two country comparison makes drawing lessons somewhat speculative, the coincidence of events suggests that these trends in Canada warrant, if not immediate action, at least careful monitoring. PMID- 2925304 TI - New from WHO: AIDS Technical Bulletin. PMID- 2925305 TI - Community mental health care in Grenada. AB - In Grenada, community mental health (CMH) care as an essential element of comprehensive primary health care goes beyond the boundaries of the psychiatric hospital and interfaces with the communities it serves. The boundaries between these two services however remain flexible and there often exists an interdependent relationship, with each acknowledging and utilizing the specific services provided by the other. This collaboration has been greatly facilitated by the fact that one administrative body is in charge of the entire mental health system throughout Grenada. PMID- 2925306 TI - How NNA international departments work. AB - Nurses and their national nurses' associations (NNAs) cannot afford to remain isolated from the world around them. This fact is widely accepted. But how many NNAs have taken the initiative to formalize their international relations rather than depend upon occasional attendance at a worldwide conference and haphazard contacts. To help NNAs that are contemplating or setting up an international department, INR reviews the objectives and operations of these departments at the Royal College of Nursing and the Canadian Nurses Association. Next, the spotlight will be on NNA international departments in Denmark, Norway and Japan. PMID- 2925307 TI - Coping with change. AB - The human brain is geared to detecting change, yet we often fear change. This may be because fear of change and a failure to cope with the change come from feeling that the origins of change are out of our control. Rather than coping with change, nurses should be effecting change in order to ensure the best patient care and their own professional autonomy. Below, the author takes an inward look at how institutions and traditional practices perpetuate these feelings and at the remedies. PMID- 2925308 TI - Priority research for health for all. AB - A main aim of the European Nursing Conference in Vienna in June 1988 was to stimulate nurses into action to help realize WHO's ambitious targets for European countries by the year 2000. Nurses in the region, it is hoped, are now following up on the Conference declaration and recommendations (INR, Sept/Oct 1988, p. 130). As action requires knowledge, research has been afforded a top role in the health-for-all movement and nurses can make a valuable contribution. A review of the targets and some of the main research areas needed to achieve them are given below not only to assist researchers in the European Region and industrialized countries tries but also to alert nurse researchers in other lesser developed countries of research areas that may soon also become "high priority." PMID- 2925309 TI - WHO Europe: AIDS and tobacco still top problems. PMID- 2925310 TI - Recurrent HSV-1 corneal lesions in rabbits induced by cyclophosphamide and dexamethasone. AB - Herpes simplex virus type 1 (HSV-1) ocular shedding and recurrent corneal epithelial lesions were assessed following an intravenous injection of cyclophosphamide (75 mg/kg) and 24 hr later an intravenous injection of dexamethasone (4 mg/kg) in 24 eyes of 15 rabbits latently infected with HSV-1 strain McKrae. Sampling for HSV-1 ocular shedding and epithelial lesion began on the day after cyclophosphamide injection and continued for 8 consecutive days. Ocular tear film was collected on a Dacron swab with care taken to avoid swabbing the corneal epithelium. Slit-lamp biomicroscopic examination was used to observe and characterize induced HSV-1 corneal epithelial lesions as deep punctate keratitis, dendritic keratitis or geographic epithelial defects. The ratio of positive days of epithelial lesions per total days was 82/187 (44%). There were 32 deep punctate lesions, 17 dendritic lesions, and 33 geographic epithelial defects. The ratio of positive swabs per total swabs was 78/187 (42%). Of the 82 positive lesion days, 54 (66%) were associated with a positive swab. Of the 78 positive swabs, 54 (69%) were associated with an epithelial lesion. Of the 54 days of both positive lesion and swab, 16 (30%) were associated with a dendritic lesion. By chi-square analysis, there was a significant association between HSV-1 swabs and HSV-1 lesions (P less than 0.001). These results confirm that intravenous injections of cyclophosphamide and dexamethasone induce both HSV-1 ocular shedding and recurrent herpes simplex corneal lesions in rabbits latently infected with HSV-1 strain McKrae. PMID- 2925311 TI - Role of fibronectin and fibrinogen in healing of corneal epithelial scrape wounds. AB - A provisional fibronectin (Fn)-fibrinogen (Fg) matrix forms de novo on the bare basement membrane (BM) surface of superficial epithelial scrape wounds in rabbit and guinea pig (GP) corneas. We determined whether such a substrate is essential for epithelial cell adhesion and migration, using three different approaches. (1) Polyclonal and monoclonal IgG reactive against GP Fn were topically administered to inhibit Fn formation in a GP epithelial scrape wound model. Immunofluorescence studies showed that deposition of both Fn and Fg was inhibited in antibody treated corneas. During the first 38 hr after wounding, the healing rates were 0.46 +/- 0.06 mm2/hr in control eyes, 0.43 +/- 0.05 mm2/hr in those treated with rabbit polyclonal IgG anti-GP Fn and 0.45 +/- 0.09 mm2/hr in those treated with murine monoclonal IgG anti-GP Fn (P greater than 0.4). (2) In a rabbit epithelial scrape wound model, ancrod was administered intravenously to induce systemic Fg depletion. Fg deposition was completely inhibited on the wound surface, but Fn deposition was not suppressed. The healing rate was 1.24 +/- 0.41 mm2/hr in ancrod-treated corneal wounds and 1.19 +/- 0.29 mm2/hr in control eyes during the first 48 hr after wounding (P greater than 0.5). These data from the antibody and ancrod inhibition indicate that Fg binds to Fn and that Fn binds to components other than Fg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2925312 TI - Role of fibronectin in the healing of superficial keratectomies in vitro. AB - A fibronectin (Fn)-fibrinogen (Fg) surface matrix is not essential for epithelial cell migration in a corneal epithelial scrape wound model, in which the basement membrane is preserved. We have therefore tested whether such a provisional scaffolding becomes more critical in a superficial keratectomy model, when the basement membrane is surgically removed. Exogeneous Fn at 0.3 mg/ml was added to the medium of organ cultures of rabbit superficial keratectomies. At 48 hr after wounding, the healing rate was 1.12 +/- 0.03 mm2/hr in control corneas and 1.11 +/- 0.03 mm2/hr in those cultured with Fn. At 64 hr after wounding, the healing rates were also not significantly different (P greater than 0.5). Immunofluorescence studies showed that Fn was not detectable on the surface of control corneas but could be depicted under the migrating epithelium. In corneas cultured with Fn, it diffused throughout the entire stroma but did not deposit as a surface matrix. We therefore attempted to obtain formation of a provisional Fn Fg surface matrix before establishment of the in vitro organ culture by leaving the superficial keratectomies in vivo for 8 hr, 24 hr or 64 hr. At 64 hr after wounding, their healing rate was 0.80 +/- 0.04 mm2/hr, 0.86 +/- 0.04 mm2/hr and 0.85 +/- 0.06 mm2/hr, respectively, which were not significantly different from that of contralateral ex vivo-wounded cultured corneas (0.83 +/- 0.04 mm2/hr, P greater than 0.5). Immunofluorescence studies revealed a Fn matrix on the bare surface of in vivo-wounded specimen, which was not detectable on ex vivo-wounded cultured corneas; there was also no diffuse stromal Fn.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2925313 TI - Age differences in corneal hydration control. AB - Dynamic changes in corneal thickness were measured in eight young and eight older normal subjects (mean ages 24.4 +/- 4.3 years and 71.9 +/- 7.3 years, respectively) to provide data for quantitative assessment of corneal hydration control and thereby provide information for studying age differences in this important aspect of corneal function. For each subject, pachometry data were obtained by (A) monitoring corneal recovery following hypoxic stress, and by either (B1) measuring recovery after sleep or (B2) by measuring corneal thickness in the late afternoon. The combined data from A and B1 or A and B2 were analyzed through an exponential model to provide information on the: (1) percent recovery per hour (PRPH) following induced corneal hydration; (2) open-eye steady-state (OESS) corneal thickness; (3) residual corneal swelling just before the hypoxic stress test; (4) amount of corneal edema induced by hypoxic stress; and (5) time to reach 95% recovery back to the OESS thickness level (T95%). The results show that between the two age groups, there are substantial differences in some characteristics of corneal hydration while other aspects are similar. For example, the mean PRPH values (58.9 +/- 7.8% and 34.2 +/- 6.4%/hr) were significantly higher in the younger subjects (P = 0.0002) and the mean time for 95% recovery to OESS thickness (207 +/- 42 min and 452 +/- 117 min) was significantly lower in the younger vs. the older group (P = 0.0002).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2925314 TI - Reassembly of the anchoring structures of the corneal epithelium during wound repair in the rabbit. AB - Reappearance of the structures involved in adhesion of the corneal epithelium to the stroma was studied in healing 7 mm keratectomy wounds in rabbit corneas. Corneas were taken at 48 and 66 hr, 1, 2, 3, 4, 6 and 8 weeks, and 4, 6 and 12 months post-wounding. Immunolocalization of bullous pemphigoid antigen (BPA), laminin and type VII collagen was used to determine time and sequence of appearance of hemidesmosomes, basement membrane and anchoring fibrils, respectively. Electron micrographs from three regions in the wound were used to correlate the immunohistochemical data and to quantitate the increase in basal cell membrane occupied by hemidesmosomes and the increase in basement membrane over healing time. Evidence of resynthesis of the adhesion structures was present at the wound margin before epithelial wound closure (48 hr). BPA, laminin and type VII collagen co-localized, indicating that hemidesmosomes, basement membrane and anchoring fibrils reappeared synchronously. Reappearance of the structures proceeded from wound margin to the center, and by 1 week BPA, laminin, and type VII collagen were present in discontinuous segments across the wound. From 2 weeks to 6 months, the segments became more continuous, and anchoring fibril networks were discerned at 4 weeks. Strata of type VII collagen and laminin were present within the newly synthesized stromal matrix at wound margin at 1 week, continuous across the wound bed by 2-4 weeks, and still present at 6 months; however, at 12 months, only a few strata of type VII collagen were present below the basement membrane at wound center.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2925315 TI - Proteoglycans of rabbit corneas with nonperforating wounds. AB - Rabbit corneal proteoglycans were labeled by intrastromal injection of 3H glucosamine and 35S-sulfate 1 and 2 weeks after partial-thickness radial scalpel incisions. Proteoglycans were extracted with guanidine-HCl and purified by ion exchange chromatography. Wounding caused a marked decrease in the total incorporation of labeled precursors into proteoglycans. The labeled proteoglycans were more readily extracted with guanidine-HCl after wounding. Labeled proteoglycans from wounded corneas had a larger molecular size on gel filtration chromatography than did proteoglycans from control corneas, a result of an increased amount of keratan sulfate in the large molecular size fractions. Analysis of labeled glycosaminoglycan (GAG) from guanidine-extracted proteoglycans and from the corneal tissue after guanidine-HCl extraction showed an increase in the relative amount of heparan sulfate and keratan sulfate after wounding, and a decrease in relative amount of dermatan sulfate. The 35S:3H ratio of heparan and dermatan sulfates increased after wounding, and that of keratan sulfate decreased, suggesting changes in sulfation. Degradation of labeled dermatan sulfate with hyaluronidase and with periodate revealed a 2-fold increase in iduronic acid content and 2-4-fold increase in hyaluronidase-resistant dermatan sulfate in the wounded corneas. Reduction in proteoglycan content, reduced sulfation of keratan sulfate, and accumulation of a high-sulfate, high iduronic acid dermatan sulfate are previously reported properties of proteoglycan in scar tissue from perforating corneal wounds. Demonstration of these properties in proteoglycan after wounds similar to radial keratotomy incisions suggests that deposition of scar tissue can result from wounds which do not damage Descemet's membrane. PMID- 2925316 TI - Immunity to a corneal antigen in Fuchs' heterochromic cyclitis patients. AB - Immunity to a major corneal antigen was studied in 28 Fuchs' heterochromic cyclitis patients and compared with the response of 44 patients with other types of uveitis and 19 healthy controls. The highest incidence of immune response was found in patients with anterior segment involvement only (anterior uveitis and Fuchs') whereas the frequency of anti-corneal immune response in patients with posterior segment involvement only was low and not significantly different from that of healthy controls. Cellular immunity to corneal antigens was found in the majority of Fuchs' heterochromic cyclitis patients, and in one-third of the anterior uveitis patients. No correlation could be established in these patients between a positive cellular response and the chronicity of the disease or the presence of keratic precipitates. Humoral immunity to the corneal antigen was also the highest in patients with anterior segment involvement, but there was no difference in response between Fuchs' and non-Fuchs' anterior uveitis patients. This study suggests that anti-corneal immunity may be triggered in inflammatory diseases of the anterior segment, especially in Fuchs' heterochromic cyclitis. PMID- 2925317 TI - Biochemical evidence for cholinergic activity in retinal blood vessels. AB - Blood vessels from human, cat, pig and bovine retinas were analyzed for their contents of choline acetyltransferase (ChAT) and muscarinic binding sites. ChAT was measured by the synthesis of 3H-acetylcholine in the presence of 3H-acetyl CoA and choline. Muscarinic binding sites were determined by the specific binding of 3H-quinuclidinyl benzylate (3H-QNB). Tissue levels of ChAT varied from 39-850 nmol/g/hr, the lowest values being in human tissues. Muscarinic binding sites were less different (0.5 to 1.8 fmol/mg net weight) among the species studied, being the highest values in human retinal vessels. It appears that retinal blood vessels not only have sites to bind acetylcholine, perhaps to mediate physiologic responses, but might be capable of supplying acetylcholine for local vascular tone control. PMID- 2925318 TI - Analysis of newly synthesized Bruch's membrane proteoglycans. AB - Bruch's membrane may provide a selective filtration barrier for nutrients coming from the choriocapillaris to the outer retina. Because proteoglycans have been shown to have structural and filtration properties in other tissues, we have been investigating the deposition of newly synthesized proteoglycans into Bruch's membrane and how these may be affected by aging and pathology. Proteoglycans deposited in human Bruch's membrane were metabolically labelled with 35SO4 and 3H glucosamine using a whole-eye organ culture system. Labeled proteoglycans were extracted from dissected Bruch's membranes with 4 M guanidine and isolated by ion exchange column chromatography on DEAE cellulose using a linear salt gradient. These molecules were subsequently chromatographed on Sepharose CL-4B and glycosaminoglycan content characterized by enzymatic and chemical degradation. The elution profiles for proteoglycans remains relatively unchanged with age, although in eyes from donors over age 70 there is a small change in size distribution toward higher molecular weights. However, the proportions of newly synthesized glycosaminoglycans remain unchanged with age, being approximately 75% chondroitin sulfate/dermatan sulfate and 25% heparan sulfate. Bruch's membrane proteoglycans from donors with different retinal pathologies, however, exhibited an increased proportion of heparan sulfate. Considering the structural and filtration properties of proteoglycans, such alterations could result in abnormal functioning of Bruch's membrane that could ultimately affect the maintenance of the outer retina. PMID- 2925319 TI - Ocular blood flow in unilateral carotid stenosis and hypotension. AB - Ocular blood flow was measured in the juxtapapillary choroid, retrolaminar optic nerve and ciliary body mesoderm using 14C-labelled iodoantipyrine with quantitative autoradiography in seven anesthetized baboons in an experimental model of cerebral and ocular ischemia induced by hemorrhagic hypotension following unilateral common carotid stenosis, with external carotid ligation. The eyes of seven baboons with unilateral common carotid occlusion were also examined histologically for evidence of structural changes. This autoradiographic method allowed measurement of blood flow in different ocular structures and a significant change was noted in the optic nerve of stenosed animals, without structural damage. PMID- 2925320 TI - Effect of dicarboxylic acids (C6 and C9) on human choroidal melanoma in cell culture. AB - In cell culture, azelaic acid (C9) has been shown to have an antiproliferative and cytotoxic effect on human and murine malignant cutaneous melanocytes. Normal melanocytes are unaffected, as are normal choroidal melanocytes. Here, effects on cell kinetics and ultrastructure of cells of a human choroidal melanoma line have been studied. Cells were exposed to single doses of disodium salts of azelaic (C(9)2Na) and adipic (C(6)2Na) acids at concentrations of 10(-2) M and 5 X 10(-2) M for 48 hr. C(9)2Na at 5 X 10(-2) M had a significant effect on proliferation at 24 and 48 hr and this was not reversible on removal of diacid. At 5 X 10(-2) M for 24 hr, C(6)2Na had no effect and at 5 X 10(-2) M for 48 hr had an effect which was marginally significant, but reversible. Swelling and disruption of mitochondria was seen in cells exposed to C(9)2Na at 5 X 10(-2) M for 1 hr and longer, but even at 10(-1) M, cells exposed to C(6)2Na were minimally affected. The results could encourage further investigations of the feasibility of azelaic acid therapy for uveal and ocular adnexal melanoma. PMID- 2925321 TI - A cell line derived from non-neoplastic human neuroretinal cells. AB - We have derived a cell line from an epiretinal membrane excised surgically from a premature female infant born at a gestational age of 25 weeks, and who developed stage 5 retinopathy of prematurity. The cell line, which in early passages appeared immunocytochemically to contain cells with both neuronal and glial characteristics, has been maintained in culture for 14 months at the time this manuscript was submitted, and has survived 20 passages. The cells have a diploid, human karyotype, with most cells possessing 46 normal appearing chromosomes, including 44 autosomes and two X-chromosomes. Morphologically, the cell line at early passages consisted of polygonal cells and also of cells possessing long, spindly branching processes. These two cell types were cloned. Nearly 100% of the cells of both morphologic types in mixed cultures stained immunocytochemically for neuron-specific enolase (NSE), a neuronal marker, and approximately 5-10% of the cells in mixed cultures (including about 50% of the cells with the spindly morphology, that were less prevalent in mixed cultures) stained for glial fibrillary acid protein (GFAP), a glial marker. We have not performed "double label" immunocytochemistry, but it was evident from the proportion of cells that stained with each marker that many cells must contain both GFAP and NSE. At least 50% of the cells in most of the early cultures were positive for keratin, while all were (and remain) negative for muscle actin. No cells are found that are immunocytochemically positive for factor VIII, a vascular endothelial cell marker. These cultured cells have also been studied immunocytochemically for their production of extracellular matrix substances. The cultures are immunocytochemically positive for type IV (but not type I) collagen, laminin and fibronectin. In later passages, cells of both clones lost their immunocytochemical positivity for GFAP and NSE, and all became positive for keratin. Cells of both clones also developed a similar, polygonal morphology, lacking long processes. By electron microscopy, many of the cells were seen to possess nonmotile cilia, with a 9 + 0 pattern of microtubule doublets. This cell line may be useful for studies of human retinal cell development and metabolism, and responses to pathological processes. PMID- 2925322 TI - Cytochemical studies on pathological Muller cells after argon laser photocoagulation. AB - The cytochemical localization of G6Pase activity, which is specific to the endoplasmic reticulum (ER) of Muller cells, was studied after argon laser photocoagulation in the guinea pig retina. After argon laser radiation, Muller cells exhibited enlargement of the cytoplasm, an increase of reactive ER and the nuclei, dislocation of the nuclei and diagonal stretching of the cytoplasm. However, cell attachment between Muller cells and the proliferated pigment epithelial cells or Bruch's membrane differed with the degree of retinal coagulation. This histo- and cytochemical method may be useful for examining Muller cells under various pathological conditions. PMID- 2925323 TI - A comparison of CW Nd:YAG contact transscleral cyclophotocoagulation with cyclocryopexy. AB - The cyclodestructive and inflammatory effects of CW Nd:YAG contact laser were compared to those of conventional cryopexy. CW Nd:YAG light transmitted by fiber optic cable and sapphire crystal was applied transsclerally to the ciliary body of pigmented and albino rabbits. Cyclocryopexy was given to a comparable second group. The intraocular pressure (IOP), flare, iritis, cells and conjunctival hyperemia were monitored clinically up to 3 weeks. The breakdown of the blood aqueous barrier and time course of ocular inflammation was similar for both modalities and IOP was -12.2 +/- 4.2 mm Hg for laser cyclopexy and -15.1 +/- 5.4 mm Hg for cyclocryopexy at 3 weeks. Ciliary body lesions were noted in both groups. Overall, albino rabbits showed less histological damage and faster recovery of IOP. Contact cyclophotocoagulation and cyclocryopexy can be considered models of ocular injury. The similarities in ocular irritative response suggest a similar pathophysiologic mechanism underlying the pressure behavior in both thermal mode injuries. PMID- 2925324 TI - Ultrastructural changes in the aqueous outflow apparatus of beagles with inherited glaucoma. AB - Spontaneous glaucoma in the beagle was exhibited after 6 months of age by elevated intraocular pressures and open iridocorneal angles followed by secondary changes. In order to appreciate alterations of the aqueous outflow apparatus in dogs with this autosomal recessive disorder, the eyes of beagles with inherited glaucoma at ages 1 day through 34 months were examined by light, scanning and transmission electron microscopy. Developmentally, no notable differences were observed between normal and preglaucomatous outflow channels through 7 months of age. In 12-month-old glaucomatous chamber angles clustered basement membrane-like material was found scattered throughout the outer corneoscleral trabecular meshwork. In this region elastin-like fibers appeared to be more numerous and arranged less regularly than age-matched normal eyes. Occasional trabecular cells within the corneoscleral trabecular meshwork possessed small clusters of serrated, opaque rods within their cytoplasm. In the older glaucomatous dogs these changes were more generalized and extensive throughout the entire corneoscleral trabecular meshwork. In some individual eyes the anterior chamber angles were observed to be narrow both clinically and histologically. These outflow apparatuses were additionally characterized by compressed, less organized trabeculae with a concomitant build-up of extracellular materials. No correlation was found between the shallowness of the iridocorneal angle and increase in intraocular pressure. Primary glaucoma in the beagle during its earlier phases compared more positively to open-angle glaucoma in man than any of the other spontaneous types in animals. PMID- 2925325 TI - Aging and rates of lens-cell differentiation in vivo, measured by a chemical approach. AB - We describe a direct and comparatively rapid chemical approach for quantitating rates of lens epithelial cell differentiation in vivo and apply it to a study of the basis of the precipitous decrease in the rate of lens growth in the rat between about 1 and 6 weeks of age. Rates of terminal differentiation of epithelial cells into fiber cells were quantitatively described by a first-order fractional rate constant (k) for loss of 3H-DNA (labeled from injected 3H thymidine) from the capsule (epithelium) to fiber cells. The rate constant (expressed in days) was calculated using the half-life estimated from semilogarithmic plots of the percent of total lens 3H-DNA measured in the capsule fraction versus time after injection of 3H-thymidine. The rate constant decreased from about k = 0.18 day-1 at 6 days of age to about 0.09 day-1 at 18-20 days of age and changed little thereafter. The decrease in lens growth at very early ages in the rat is at least partially due to decreases in rates of epithelial cell differentiation. PMID- 2925326 TI - Visual field development in infants with stage 3 retinopathy of prematurity. AB - Binocular visual field development was measured in 11 infants who had stage 3 ROP in early infancy and in 11 infants without ROP, matched for birthweight and gestational age. Kinetic perimetry was used to measure visual fields along the 45 degree, 135 degree, 225 degree and 315 degree half-meridia. Infants were tested at 4, 9, and 18 months from due date. Analyses of variance were used to compare results of the two groups for each age tested. Results at the 4-month test age indicated that both groups had visual fields within the normal range for their age. However, at the 9-month test age the ROP group showed a significantly (P less than 0.05) smaller visual field than the control group. At 18 months, the ROP group still showed smaller visual fields than the control group, but the difference was not significant. The results suggest that dysfunction of the peripheral retina associated with ROP may produce a constriction of the visual field or a delay in visual field development. PMID- 2925327 TI - Iontophoresis of 5-fluorouracil into the conjunctiva and sclera. AB - It was investigated in the rabbit eye whether the method of iontophoresis could introduce a sufficient amount of 5-fluorouracil (5-FU) to inhibit fibroblast proliferation into the conjunctiva and sclera, thus considerably reducing the total amount of 5-FU which must be given to the eye. Five-FU was introduced with a simple apparatus which was filled with 5% 5-FU solution and connected to the negative pole of a current source. When the apparatus was placed over the cornea, the 5-FU penetration into the cornea showed a correlation with strength of current (0-0.75 mA). When the apparatus was placed over the bulbar conjunctiva, a sufficient amount of 5-FU to inhibit fibroblast proliferation was introduced into the conjunctiva and sclera with a current of 0.5 mA passed for 30 seconds. Immediately after iontophoresis, mean 5-FU concentrations in the conjunctiva and sclera at the iontophoresis site were 480 and 168 micrograms/g, respectively. They decreased to 0.6 and 1.2 micrograms/g by 10 hr, but were still above the reported ID50 levels for the cultured conjunctival fibroblast. On the other hand, the total amount of 5-FU introduced into the eye averaged only 3.7 micrograms and the current used was much lower than that formerly applied to the patient's cornea. PMID- 2925328 TI - Transplanted retinal pigment epithelium modifies the retinal degeneration in the RCS rat. AB - Transplantation of dissociated retinal epithelial cells obtained from the retinas of normal, congenic pigmented strain of rats to Bruch's membrane and the subretinal space of dystrophic rats from the Royal College of Surgeon (RCS) strain can prevent photoreceptor cell degeneration in this retina for at least 4 months after transplantation. Host and transplant cells form close apposition with one another but can be distinguished by the presence of both phagosomes and melanin granules in the transplant and the absence of these inclusions in the host retinal epithelium. Transplanted cells show excessive amounts of phagosomal material within 48 hr after transplantation, implying that restoration of phagocytosis is responsible for the photoreceptor survival. PMID- 2925329 TI - The Association for Research in Vision and Ophthalmology, annual spring meeting. Sarasota, Florida, April 30-May 5, 1989. Abstracts. PMID- 2925330 TI - Registered nurse shortage: a health care crisis. PMID- 2925331 TI - RCTs: a physician's viewpoint. PMID- 2925332 TI - Hyperbaric oxygen therapy. AB - The author describes the history of and potential medical uses for hyperbaric oxygen (HBO) therapy, a useful adjunct to more established therapies. PMID- 2925334 TI - Meeting the emerging employee shortage. PMID- 2925333 TI - Serum cholesterol of residents in north Iowa. AB - A survey of serum cholesterol levels was done on 219 residents in north Iowa. Population reference values of serum cholesterol for the community were developed. Data indicate age is an influential factor in both sex groups. Consumption of oral contraceptives appears to be a significant factor in increased serum cholesterol levels in females. Although cigarette smoking seems to augment serum cholesterol level superficially, its relationship is not statistically significant in the study. PMID- 2925335 TI - Medicated aerosol delivery. AB - Recent literature abounds with data which supports the need to give greater consideration to the metered dose inhaler as a therapeutically effective and more cost effective method of in-hospital aerosolized bronchodilator delivery. Patients are increasingly asked to assume a larger role in their own care following discharge, making opportunities such as in-hospital self-administered aerosol therapy too important of a tool to pass up. Hospitals are under increasing pressure to provide a greater range of health care services with existing resources. Existing procedures such as medicated aerosol therapy which can be provided as effectively but more efficiently in an alternative fashion while increasing patient involvement in their own care can simply no longer be overlooked. PMID- 2925336 TI - The shortage of nursing personnel. PMID- 2925337 TI - An important alliance. PMID- 2925338 TI - Pharmacy/medicine interface. PMID- 2925339 TI - Nursing shortage: focusing on priorities. PMID- 2925340 TI - Board of pharmacy examiners: an overview. PMID- 2925341 TI - Subacute subdural hematoma presenting as reversible ischemic attacks. AB - We describe the case of a right-handed, 83 year-old woman with CT-documented left frontal subacute subdural hematoma showing reversible right-sided hemiparesis and aphasia. We discuss possible pathogenetic mechanism for this unusual condition and emphasize that the clinical evaluation cannot always distinguish ischemic causes for certain. Therefore CT-scan is an essential investigative tool before initiating therapy in patients suspected of having cerebrovascular diseases. PMID- 2925342 TI - Lead poisoning during heroin addiction. AB - We describe the case of a young man addicted to heroin with the clinical pattern of symmetrical brachial neuropathy, without other neurological involvement. Lead poisoning was detected and chelating therapy induced a marked improvement of the clinical symptoms. The possible toxic effect of heavy metals in the pathogenesis of brachial and lumbar plexopathies during heroin addiction has previously been suggested by other authors, but never detected. PMID- 2925343 TI - Multiple sclerosis intra-blood-brain-barrier IgG synthesis: effect of pulse intravenous and intrathecal corticosteroids. AB - Nine severely disabled clinically definite chronic progressive multiple sclerosis (MS) patients who had at least one determination of intra-blood-brain-barrier (BBB) IgG synthesis rate of greater than 7 mg/day (upper limit of normal = 3.3) participated in this study. Seven patients were given 1 gram of methylprednisolone sodium succinate (MP) by intravenous infusion over 30 minutes once a day for 3 days. Statistically significant (p less than .05) reduction in intra-BBB IgG synthesis (mg/day) was seen in 4/7 patients, but in only 2 were normal levels of synthesis rate (less than 3.3 mg/day) attained. Rebound of IgG synthesis to premedication rates occurred within 30 days in 2/4 patients. There was no change in intensity or pattern of cerebrospinal fluid (CSF) oligoclonal IgG bands by isoelectric focusing, immunofixation, and silver staining. A subsequent course of intrathecal methylprednisolone acetate (MPA) (80 mg twice a week for 5 weeks) was given to 5 of the 7 patients and to 2 additional patients not previously treated. In spite of signs of subarachnoid inflammation, a statistically significant depression of intra-BB synthesis, which far exceeded that from the pulse treatment occurred in all 7, including the 2 patients whose intra-BBB IgG synthesis rates were previously resistant to pulse steroid administration. Normal levels of synthesis were rapidly reached in 4/7 patients; however, an IgG synthesis rebound occurred in 3/7 patients which was just as rapid. One out of 7 patients showed a temporary reduction in the number of cathodic IgG oligoclonal bands in the CSF. Two patients required discontinuation of treatment due to aseptic meningitis in one and progressive weakness in the other. Clinically, these severely afflicted patients with fixed deficits remained unchanged with either treatment protocol. While MPA and ACTH have similar initial effect on the central nervous systems (CNS) inflammatory response in MS, the well documented risk of serious adversities with MPA prohibit its clinical use in MS in its present form. PMID- 2925344 TI - Experimental allergic encephalomyelitis in guinea pig: variability of response to intradermal emulsion injection. AB - Different forms of experimental allergic encephalomyelitis were obtained in 4 groups of guinea pigs: 7 adult Hartley guinea pigs (Group I), 12 adults of the same strain (Group II), 6 juvenile strain 2 guinea pigs (Group III) and 6 juvenile strain 13 animals (Group IV), by the injection of emulsions. Groups I and II received emulsions containing 250 mg and 500 mg respectively of fresh isologous spinal cord tissue, complete Freund adjuvant (CFA) and saline solution while Groups III and IV received an emulsion containing 120 mg of isologous spinal cord, CFA, saline solution and 15 mg of Mycobacterium tuberculosis. The increased antigen load induced a disease with delayed onset and prolonged progressive course (C-P-EAE) in Groups I and II, although 8 animals showed no symptoms of illness. The findings in C-P-EAE were large demyelinated plaques, perivenous fibrosis and large areas of infiltration. Demyelinated areas occurred within the spinal cord white matter only in two asymptomatic animals. C-P-EAE was obtained in 4 of the Strain 2 animals. In conclusion, the increased antigen load induced a range of lesions in Hartley guinea pigs, although not all animals were affected. C-P-EAE was induced also in strains of guinea pig other than the Heartley strain. These different reactions may have been the outcome of partial or complete inactivation of the cell-mediated response to the inoculated antigens. PMID- 2925346 TI - Multimodality evoked potentials in myotonic dystrophy. AB - Multimodality evoked potentials were performed in 18 patients affected by myotonic dystrophy (8 males and 10 females); the aim was to make an electrophysiological evaluation of the central nervous system involvement in this disease. We observed brainstem, somatosensory and visual evoked potential abnormalities respectively in 53%, 62.5% and 71.4% of cases, with no apparent relationship to the severity of the disease. Our abnormal findings provide further confirmation of CNS involvement in myotonic dystrophy and occur in various combinations suggesting an aspecific involvement at different levels, reflecting the multisystemic character of this disease. PMID- 2925347 TI - Normal muscle mitochondrial function in Ramsay-Hunt syndrome. AB - Mitochondrial encephalomyopathies may display clinical features similar to Ramsay Hunt syndrome (RHS). We studied muscles mitochondrial function in 2 patients with RHS. Histochemical and ultrastructural studies of muscle biopsies and biochemical analysis of muscle mitochondrial enzymes were normal. There is no evidence for a disturbance of muscle mitochondrial function in RHS. PMID- 2925345 TI - Hyperthermic syndromes and impairment of the dopaminergic system: a clinical study. AB - We present 8 cases of centrally-originating hyperthermic syndrome, the initial cause being either neuroleptic malingnant syndrome, hyperthemia after discontinuance of antiparkinsonian therapy or heatstroke. We review the physiological and neurochemical mechanisms involved in thermoregulation, emphasizing the role of dopamine. A single mechanism, consistent with pharmacological or neuropathological impairment of the dopaminergic system, could be responsible for all the cases of hyperthermic syndrome presented. PMID- 2925348 TI - Brainstem encephalitis due to Listeria monocytogenes. Favourable outcome after early antibiotic therapy. AB - A case of brainstem encephalitis is reported in which an early identification in blood of listeria monocytogenes allowed an effective antibiotic therapy (Ampicillin and Gentamicin) with complete recovery. PMID- 2925349 TI - Drug-induced tremor of the tongue. AB - Two cases are reported in which a transient tremor of the tongue followed treatment with thioridazine and flunarizine. The finding of this kyperkinesia as the only extrapyramidal side-effect of drug therapy is uncommon. PMID- 2925350 TI - Aphasia and apraxia caused by ischemic damage to the white substance of the dominant hemisphere. AB - We describe a case of aphasia associated with ideomotor apraxia due to a CT proven ischemic lesion strictly confined to the dominant hemisphere white substance at the junctional zone of Donnan. The aphasia did not fit any of the known patterns. At first severe, it cleared in 5 days, while the apraxia remained unchanged 25 days after onset. PMID- 2925351 TI - Branched chain amino acids in the protection of myocardium from ischemic damage. PMID- 2925352 TI - Development and decay of systemic thermotolerance in rats. AB - The development and decay of thermotolerance to the lethal effect of systemic hyperthermia was investigated in Sprague-Dawley rats. Systemic hyperthermia was induced by partial submersion of gas-anesthetized rats into a temperature controlled water bath. Survival was determined in rats challenged for periods of 10 to 90 min at 42.5 C, 24 to 144 h after a sublethal conditioning exposure of 41.8 C for 1 h. Survival curves of various exposure times at 42.5 C lethal to 50% of the animals (LD50) were determined for the conditioned animals and compared with those obtained for simultaneously treated control (unconditioned) rats. The thermotolerance ratios (TTR-LD50 for conditioned animals at various times after sublethal conditioning exposure divided by the LD50 for the control animals) were calculated and compared with the ratios reported in the literature for cells heated in vitro and for tissues heated locally in vivo. Pretreatment of rats at 41.8 C for 1 h resulted in an increase in the LD50 when rats were challenged 24 to 96 h later, with a maximum increased noted at 48 h (56.5 vs. 25.0 min for control; TTR = 2.3). The animals remained relatively resistant to the second heat treatment at 96 h and returned to control levels of heat sensitivity by 120 h. The development and kinetics of thermotolerance to lethality induced by whole body hyperthermia need to be considered when multiple-fraction hyperthermia treatment plans are designed. PMID- 2925353 TI - Extra-anorectic actions of mazindol. AB - In the search for mechanisms supporting the weight-reducing effect of mazindol, we examined the influence of the drug on metabolism and gastric evacuation in two groups of 10 women each. In the first group the effect of mazindol on thermogenesis was assessed by indirect calorimetry, and blood glycerol concentration was taken as an index of lipolysis. After oral administration of 2 mg mazindol no significant changes were observed in the energy expenditure or lipolysis, either at rest or during exercise. In the second group, the influence of 2 mg mazindol, taken orally, on gastric emptying (GE) of a radiolabeled solid meal was examined with the use of a gamma camera. The drug significantly inhibited GE--the median GEt1/2 was 119 min after placebo vs. 230 min after mazindol. The mean +/- SE of the emptying index was 1.13 +/- 0.26 min-1 after placebo vs. 0.53 +/- 0.14 min-1 after mazindol. Mazindol elicited a delaying effect on the late phase of GE, as confirmed by a significant decrease of the shape parameter (S) of the power-exponential fitted GE curves, 2.09 +/- 0.22 after placebo vs. 1.61 +/- 0.24 after mazindol, and by the comparison of the amount of food emptied from the stomach: 30.7 +/- 6.1% after placebo vs. 17.8 +/- 4.0% after mazindol, at 80 min, and 38.9 +/- 6.2% after placebo vs. 20.6 +/- 4.3% after mazindol, at 90 min of the GE measurement. PMID- 2925354 TI - Results and relevance of urodynamic studies in the management of urinary incontinence in women over eighty. AB - Urinary incontinence among the elderly is a major problem that is often neglected. The results of urodynamic studies in a group of 32 women greater than 80 years old with incontinence revealed that detrusor instability was the primary cause of incontinence in 23 (72%), while 9 (28%) patients demonstrated signs of sphincter incompetence. Urodynamic study results were normal in four patients. Medical treatment on a self-regulated dose and bladder training were effective in controlling incontinence in 25 (78%) of the study group. It is suggested that, although detrusor instability is the major cause of incontinence in elderly women, urodynamic studies should be performed for accurate diagnosis to ensure optimal therapeutic results. PMID- 2925355 TI - Hyperbilirubinemia and influencing factors in term infants. AB - The development of jaundice was investigated in 275 consecutive full-term infants and determined longitudinally in each neonate. The mean peak of bilirubin was 7.90 +/- 0.20 mg/dl observed at 64.0 +/- 1.3 h of life. Three factors were found to significantly alter the course of hyperbilirubinemia: first and second bilirubin determinations (at 2 to 4 h and 12 to 24 h, respectively), weight loss and male sex. Increased weight loss was positively correlated with hyperbilirubinemia irrespective of the mode of feeding. PMID- 2925356 TI - Protective effect of branched chain-enriched amino acid formulation in myocardial ischemia. AB - The protective effect of a branched chain amino acid (BCAA) formulation on the ischemic myocardium was determined in four groups of passively perfused normothermic (37 C) isolated rat hearts perfused with Krebs-Henseleit (KH) or KH + BCAA. Time to ischemic contracture was significantly increased by the infusion of BCAA compared with KH (19.4 +/- 2.3 vs. 15.9 +/- 1.7 min). In a second set of experiments, rat hearts were perfused with KH or KH + BCAA solution followed by 2 min of glucose-free KH buffer. After 17 min of ischemia, both groups were reperfused for another 15 min. Percent of pressure recovery was significantly better with KH + BCAA (90.1 +/- 8.4) than with KH (56.4 +/- 40.0). Percent +dP/dt (time derivative of pressure at contraction) recovery was also significantly improved with KH + BCAA (96.5 +/- 26.9 vs. 58.1 +/- 44.0). Furthermore, arrhythmias were minimized by BCAA. There was no difference in change of coronary flow between these two groups. Thus, BCAAs appear to protect the heart against myocardial ischemic injury and to delay the time to ischemic contracture, particularly in the depleted ischemic heart. BCAAs enhance postischemic pressure recovery and improve postischemic systolic and diastolic myocardial function. PMID- 2925357 TI - Primary care utilization in Israel--analysis of national data. AB - Analysis of data from the 1981 National Health Services Utilization Survey was carried out in order to identify factors relevant to primary care utilization in Israel on a semi-quantitative basis. The analysis consisted of stratification of the sample population into age- and sex-groups and the use of a logistic regression model for each stratum. Within the strata age still played a major role in explaining the probability of utilization; in addition, origin, employment status and education were also significant for most strata. In men aged greater than or equal to 65, living arrangements (alone, with spouse or with children) affected utilization. These findings were consistent with previous published reports and with findings of small-scale studies in Israel. PMID- 2925358 TI - Meningitis in Israel: an imported outbreak. PMID- 2925359 TI - Home shower-bath Pseudomonas folliculitis. PMID- 2925360 TI - Pulmonary infiltrate in acute toxoplasmosis. PMID- 2925361 TI - Centipede (Scolopendra) bite: a case report. PMID- 2925362 TI - Dwarfism with congenital bowing of long bones. PMID- 2925363 TI - Topical application of chloramphenicol eye ointment followed by fatal bone marrow aplasia. PMID- 2925364 TI - Straining forces at bowel elimination. PMID- 2925365 TI - Nurse-client perceptions: the double standard of touch. AB - Because nurses have been cited as being unaware of clients' nonverbal communication as well as their own (Blondis, 1977; Murphy, 1984), the purpose of this descriptive study was to determine if 80 adult surgical clients' and 80 female registered nurses' perceptions about intrusions of hospital territory and personal space differed. Differences according to gender of client were specifically examined. The investigator administered the Territorial Intrusion Personal Space (TIPS) Scale questionnaire to measure various feelings in response to intrusions. T-tests revealed that male clients generally had higher scores on the personal space subscale than nurses anticipated, whereas female clients had lower scores than nurses anticipated. These results revealed a double standard of touch: Male clients interpreted touch from a female nurse more positively than did female clients; however, female nurses interpreted female clients' behavior as being more receptive to touch and therefore appeared to be more comfortable touching female than male clients. PMID- 2925366 TI - The "will to live" as perceived by nurses and physicians. AB - This study investigated the "will to live" as nurses and physicians perceive it. A sample of 221 practicing health professionals completed a questionnaire that was designed to measure this construct. Semantic differential scales were used to assess the psychological characteristics of patients with a strong and weak will to live, while Likert scales were used to rate overt behaviors associated with a strong will to live. The respondents were also asked to rate activities that might be used to strengthen the will to live in patients who lacked it. Results showed that almost 100% of the respondents believed in a will to live, had observed its effects, and felt that a strong will to live was an important factor in patient recovery. Both nurses and physicians showed surprising agreement in their perception of the will to live, as well as in their suggestions about how to strengthen patient morale. The results are generally consistent with those from related studies on psychological variables associated with cancer survival and recovery from catastrophic illness. It is concluded that regardless of whether a will to live is a "real" attribute of patients, it certainly seems to exist in the eyes of those who treat them. PMID- 2925367 TI - Construct validity of an aspect of the coping process: potential adaptation to stress. AB - The focus of this study was to examine construct validity of the Adaptive Potential Assessment Model (APAM). Incorporated within a larger theory and paradigm entitled Modeling and Role-Modeling, APAM depicts three main states, arousal, equilibrium, and impoverishment; each state represents a different potential to mobilize coping resources. Arousal and impoverishment are considered stress states while equilibrium is considered a nonstress state. The sample was young, male students (N = 73) who were experiencing varying degrees of stress. Physiological and psychological data were gathered by utilizing several instruments and clinical assessment techniques. APAM was validated in a healthy population. Discriminant function analysis revealed motor-sensory behavior, fatigue-sadness, hope, and verbal anxiety as useful predictors in determining adaptive potential states. Misclassifications of subjects determined to be at risk by the investigator and not by the mathematical algorithm are considered. The benefits of holistically identifying clients' ability to mobilize coping resources is that nurses can plan intervention more effectively if these categorizations can be consistently verified. PMID- 2925368 TI - Social support, self-esteem, and depression in the institutionalized elderly. AB - Psychosocial studies of the elderly have been limited primarily to noninstitutionalized elderly living at home in the community. Only a few studies have explored the psychological implications of being institutionalized despite the fact that approximately 5% of the 25.6 million elderly 65 years or older in the United States reside in nursing homes (Rovner & Rabins, 1985). This correlational study was a beginning effort to investigate the relationships among depression, social support, self-esteem, and selected demographic variables in a sample of 26 institutionalized elderly individuals. The Norbeck Social Support Questionnaire (NSSQ) was used for measuring social support. The Geriatric Depression Scale (GDS) and Rosenberg's Self-Esteem Scale were used to measure depression and self-esteem respectively. The applicability of these instruments for studies of the elderly is discussed. Findings indicated that the demographic characteristics of the subjects had no significant effect on their feeling of self-esteem or depression. However, social support significantly correlated with depression and there was some indication that the type of institutional setting and frequency of religious participation also interacts with the level of depression. The article concludes with recommendations for future research. PMID- 2925369 TI - Incest: the psychological problem and the biological contradiction. AB - We have yet to map an "inbreeding avoider" gene or design a psychological test that can accurately diagnose incest transgressors. Until those events occur, sociobiology, nursing, and psychology must explain phenomena, such as the incest taboo, with a theoretical language of supposition. It is in this light that the etiology of taboo is analyzed. This article proposes that a propensity for sexual selection originates in the gene system, and what becomes taboo is acquired through the learning that accompanies the experiences of the individual and culture when sexual selection occurs. Influences of the genetic system and psychological culture on the existence of a taboo are contrasted. The conclusion posits an eclectic taboo hypothesis, derived from the congruencies found in the literature, and suggests how this hypothesis can guide nursing interventions with incestual families. PMID- 2925370 TI - The role of the therapist's critical parent. AB - The need for nurse therapists to be aware of their own feelings, beliefs, and attitudes is all-important if treatment is to be effective. In this paper, the author uses the concept of the therapist's Critical Parent (from Berne's 1961 Transactional Analysis model) to explore countertransference reactions. Clinical examples from the author's professional experience are employed to demonstrate the interplay of ego states between therapist and client and how understanding of the effect of the therapist's Critical parent can enhance his or her ability to intervene effectively. PMID- 2925371 TI - Blood flow and vascular reactivity during attacks of classic migraine- limitations of the Xe-133 intraarterial technique. AB - The present study reports cerebral blood flow (CBF) measurements in 11 patients during attacks of classic migraine (CM)--migraine with aura. In 6 and 7 patients, respectively, cerebral vascular reactivity to increased blood pressure and to hypocapnia was also investigated during the CM attacks. The Xenon-133 intraarterial injection technique was used to measure CBF. In this study, based in part on previously published data, methodological limitations, in particular caused by scattered radiation (Compton scatter), are critically analysed. Based on this analysis and the results of the CBF studies it is concluded: During CM attacks CBF appears to decrease focally in the posterior part of the brain to a level around 20 ml/100 g/min which is consistent with a mild degree of ischemia. Changes of CBF in focal low flow areas are difficult to evaluate accurately with the Xe-133 technique. In most cases true CBF may change 50% or more in the low flow areas without giving rise to significantly measurable changes of CBF. This analysis suggests that the autoregulation response cannot be evaluated in the low flow areas with the technique used while the observations are compatible with the concept that a vasoconstrictive state, unresponsive to hypocapnia, prevails in the low flow areas during CM attacks. The gradual increase in size of the low flow area seen in several cases may be interpreted in two different ways. A spreading process may actually exist. However, due to Compton scatter, a gradual decrease of CBF in a territory that does not increase in size will also appear as a gradually spreading low flow area when studied with the Xe-133 intracarotid technique. PMID- 2925372 TI - Platelet activation and analysis of organelles in migraineurs. AB - We used transmission electron microscopy to investigate selected aspects of the platelet response (surface activation as well as aggregation) and quantify cytoplasmic organelles within the cytoplasm of platelets obtained from both healthy control women and women diagnosed as having either common or classic migraine. Comparisons between controls and migraineurs showed no differences for: (1) the number of circulating platelets, (2) degree of surface activation, (3) amount of aggregate formation or (4) percent of hyperactive platelet populations. In contrast, platelets of migraine sufferers uniformly contained a significantly greater number of dense bodies compared to control platelets. Although we did not find functional abnormalities for the platelets obtained from migraineurs, we did demonstrate that they were altered structurally. PMID- 2925373 TI - Migraine and anti-phospholipid antibodies. AB - Anti-phospholipid antibodies (APA), initially described with SLE, have in recent years received much attention because of an associated increased risk of thrombo embolic disease, recurrent abortion and thrombocytopenia. Although commonly seen with SLE or other collagen vascular diseases, the antibodies frequently occur in the absence of any such disease. Neurologic complications include transient or permanent ischemic episodes, migraine or related phenomena, myelopathy and a Guillain-Barre type syndrome. In this report we describe the presenting features and clinical course of six patients with anti-phospholipid antibodies where migraine was an early and prominent symptom. All six patients, however, were recognized only after a second more serious event had occurred. As this entity becomes more widely recognized and better treatments evolve an earlier diagnosis of patients with migraine as the only manifestation of APA may prevent the development of other serious complications. PMID- 2925374 TI - Headache as a risk factor in atherosclerosis-related diseases. AB - A group of 350 migraineurs (87 male, 263 female) and 300 controls without migraine (104 male, 196 female) were questioned about occurrence, in parents, of the atherosclerosis-related diseases (ASRD) of diabetes mellitus (DM), hypertension (HBP), myocardial infarction (MI), and stroke as well as about recurrent severe headache (RSHA). Occurrence of DM, HBP, MI and stroke was compared for mothers and fathers of migraine vs. those of control subjects and no significant differences were found. The mothers and fathers were pooled and resegregated by presence or absence of RSHA and then occurrence of DM, HBP, MI and stroke again compared. For mothers there was increased occurrence of stroke and DM in the RSHA group but the differences were not significant. For RSHA fathers there was increased incidence of MI (p less than .10) and HBP (p less than .01). Aggregate occurrence of all ASRD was evaluated for RSHA vs. no-RSHA parents. ASRD occurred more frequently in the RSHA than in the no-RSHA parents (p less than .05). Breakdown by age showed that this occurred at all ages in men (p less than .05) but in women the difference was significant only under age 60 (p less than .05). This study suggests that RSHA, which is primarily migraine, may be a risk factor or a marker for occurrence of ASRD. PMID- 2925375 TI - Migraine--resuscitation of the vascular theory. PMID- 2925376 TI - Nasal plug as an aid for cluster headaches: relevance of the nasal cycle. PMID- 2925377 TI - V.E.P.'s not a marker for migraine. PMID- 2925378 TI - What drives health care today? PMID- 2925379 TI - HCMR interview: John Ferguson. Interview by Montague Brown and Barbara P. McCool. PMID- 2925380 TI - Radiological health effects models for nuclear power plant accident consequence analysis. AB - Improved health effects models have been developed for assessing the early effects, late somatic effects and genetic effects that might result from low-LET radiation exposures to populations following a major accident in a nuclear power plant. All the models have been developed in such a way that the dynamics of population risks can be analyzed. Estimates of life years lost and the duration of illnesses were generated and a framework recommended for summarizing health impacts. Uncertainty is addressed by providing models for upper, central and lower estimates of most effects. The models are believed to be a significant improvement over the models used in the U.S. Nuclear Regulatory Commission's Reactor Safety Study, and they can easily be modified to reflect advances in scientific understanding of the health effects of ionizing radiation. PMID- 2925381 TI - Influence of subsoil geology and construction technique on indoor air 222Rn levels in 80 houses of the central Swiss Alps. AB - The indoor 222Rn level depends mainly on the subsoil geology, the cellar floor permeability, the cellar aeration, the air-tightness of the homes, and the aeration habits of the occupants. These five parameters and the 222Rn levels in the cellar and in the living room on the ground floor were compiled in 80 one- or two-family houses of the central Swiss Alps. The 222Rn levels were measured with passive alpha track detectors. Houses located on a granite, ortho-gneiss or verrucano subsoil have a cellar 222Rn level that is on the average 4.4 times higher than houses which are built on grey-schist or sediments. The cellar level is on the average 5.4 times higher if the cellar has partially a gravel or earth floor than if the whole cellar surface is covered with a concrete floor. Energy efficient, highly air-tightened homes have a living room level that is on the average 1.8 times higher than normally insulated conventional homes. In the cellars and the living rooms of the 80 houses considered, arithmetic mean 222Rn levels of 724 Bq m-3 (20 pCi L-1) and 178 Bq m-3 (4.8 pCi L-1), respectively, were found. In the central Swiss Alps 222Rn and 222Rn decay products lead to an estimated mean exposure of 5.3 mSv effective dose equivalent per year. PMID- 2925382 TI - Effects of vegetation, a clay cap and environmental variables on 222Rn fluence rate from reclaimed U mill tailings. AB - We measured 222Rn fluence rate and several environmental variables on two plots with U mill tailings buried beneath 30 cm of overburden and 20 cm of topsoil. An additional 30 cm of clay covered the tailings on one plot and each plot was subdivided into bare soil and vegetated subplots. We used linear correlation, two way ANOVA and stepwise multiple regression to analyze the effects of the plot characteristics and the environmental variables on 222Rn fluence rate. The most important effect on 222Rn fluence rates from these plots was the combination of a clay cap and a vegetated surface. The mean annual fluence rate from the plot having both of these characteristics (520 +/- 370 mBq m-2 s-1) was over three times that of the vegetated plot without a clay cap (170 +/- 130 mBq m-2 s-1) and 18 times that of the bare plot with a clay cap (29 +/- 13 mBq m-2 s-1). The interaction effect may have been due to the growth of roots in the moist clay and active transport of dissolved 222Rn to the surface in water. This speculation is supported by the observation that on vegetated plots with a clay cap, moisture in the clay enhanced the fluence rate. PMID- 2925383 TI - The accuracy of some simple models for predicting particulate interception and retention in agricultural systems. AB - The accuracy of three radionuclide transfer models for predicting the interception and retention of airborne particles by agricultural crops was tested using Pu-bearing aerosols released to the atmosphere from nuclear fuel facilities on the U.S. Department of Energy's Savannah River Plant, near Aiken, SC. The models evaluated were: 1) NRC, the model defined in U.S. Nuclear Regulatory Guide 1.109; 2) FOOD, a model similar to the NRC model that also predicts concentrations in grains; and 3) AGNS, a model developed from the NRC model for the southeastern United States. Plutonium concentrations in vegetation and grain were predicted from measured deposition rates and compared to concentrations observed in the field. Crops included wheat, soybeans, corn and cabbage. Although predictions of the three models differed by less than a factor of 4, they showed different abilities to predict concentrations observed in the field. The NRC and FOOD models consistently underpredicted the observed Pu concentrations for vegetation. The AGNS model was a more accurate predictor of Pu concentrations for vegetation. Both the FOOD and AGNS models accurately predicted the Pu concentrations for grains. PMID- 2925384 TI - Artificial radioactivity in fuel peat and peat ash in Finland after the Chernobyl accident. AB - The accident at the Chernobyl nuclear power plant in April 1986 caused very uneven deposition of radionuclides in Finland. The deposited radionuclides were found in relatively high concentrations in fuel peat and especially in peat ash because a thin surface layer of peat-production bogs was extracted as fuel peat soon after the fallout occurred. Concentrations of artificial radionuclides in fuel peat and peat ash were measured at six peat-fired power plants in Finland throughout the heating season 1986-87. Concentrations of 137Cs in composite peat samples varied between 30 and 3600 Bq kg-1 dry weight and in ash samples between 600 and 68,000 Bq kg-1. High concentrations in peat ash caused some restrictions to the utilization of peat ash for various purposes. PMID- 2925386 TI - Environmental radioactivity and dose evaluation in Taiwan after the Chernobyl accident. AB - A substantial increase in fission product activity was observed in various environmental samples taken in Taiwan after the Chernobyl accident. The concentration of long-lived fission products in air above ground, precipitation, grass, vegetation and milk were monitored in the next 7 wk. The individual effective dose equivalent committed by the first year of exposure and intake following the accident were evaluated. Average individual doses for the population in Taiwan are estimated at 0.9 microSv due to global fallout from the Chernobyl accident. This value is lower than that reported in neighboring countries in the Far East and poses no increased health impact to the public in Taiwan. PMID- 2925385 TI - Cesium-137, 134Cs and 110mAg in lambs grazing pasture in NE Scotland contaminated by Chernobyl fallout. AB - The decline in Cs radioisotope levels has been studied in tissues from lambs grazing lowland pasture. The lambs were slaughtered 18 and 115 d after contamination with Chernobyl fallout. During this time the Cs activity decreased to 13% of the initial amount in animals that had continued to graze contaminated pasture and to 3.5% in animals consuming uncontaminated feed. The 137Cs concentration in grass from the field grazed by the lambs decreased with a half time of 22 d over the period 11-100 d after contamination. The amounts of Cs radionuclides removed from the pasture by the grazing animals amounted to only 0.01% of the total, the rest remaining in the soil, with over 40% in the upper 10 mm. Small amounts of 110mAg, found in grass, declined with a half-time of 8.9 d, and the radionuclide was found to accumulate in liver tissue. PMID- 2925387 TI - The biological half-time of radioactive Cs in poikilothermic and homeothermic animals. AB - Literature data for the half-time of Cs in one-, two-, and three-compartment models have been collated and regressed to yield general descriptions of clearance for homeotherms (warm-blooded animals) and poikilotherms (cold-blooded animals) of different sizes. Cesium half-times increase with body weight and are longer in poikilotherms than in homeotherms. These trends and the values of the associated regression coefficients imply that Cs clearance is a function of metabolic rate. The patterns are especially visible in analyses of the larger compartments, perhaps because the curve splitting required to analyze smaller, more rapidly cleared pools is necessarily subjective. The route by which acutely contaminated animals receive their Cs also influences clearance. Inhaled Cs appears to be retained longer than injected Cs, which is in turn retained longer than ingested Cs. This suggests that Cs is discriminated against in biological transfers, so that Cs dust remains in the lungs whereas Cs in the food is less readily absorbed. These patterns of Cs clearance suggest that large animals, poikilotherms, and animals contaminated by inhalation or injection may receive a greater dose. PMID- 2925388 TI - Influence of age at exposure on concentrations of 239Pu in beagle gonads. AB - The influence of age at injection of 239Pu on the gonadal concentrations with time after injection in beagle dogs was determined. In addition, the distribution patterns of Pu within the organs were examined using fission track autoradiography. Beagles of different ages (juveniles approximately 90 d; young adults approximately 17 mo; aged approximately 5 y) were given a single injection of 239Pu(IV)-citrate and most were allowed to live out their natural lifespan. At times greater than 1,000 d after exposure, the concentrations of 239Pu (expressed as percent injected per gram organ weight) were higher in the testes and ovaries from animals injected as young adults (median 9.8 X 10(-4) and 15.4 X 10(-4%) g 1, respectively) when compared with the juveniles (median 2.8 X 10(-4) and 7.7 X 10(-4%) g-1, respectively) or aged (median 6.3 X 10(-4) and 17.2 X 10(-4%) g-1, respectively) animals. The lower concentrations found in the animals injected as juveniles can be attributed to the increase in gonadal size that occurs during organ maturation and puberty. Fission track autoradiographs from gonadal tissues at least 5 y after exposure confirm the nonuniform distribution of the nuclide in these organs. In the testis, Pu was found mostly in the interstitial tissues and in the ovary, was found in the stroma, particularly the medullary stroma. PMID- 2925389 TI - Energy spectra of electrons and positrons produced in semi-infinite and infinite water phantoms irradiated by photons with energies up to 1 GeV. AB - Previous Monte Carlo calculations for the energy spectra of electrons produced in water irradiated by photons are extended to 1 GeV. All of the physical processes believed to be important in the transport of electrons and positrons above 100 keV and photons starting with the ejection of L photoelectrons are considered. The results are presented in tabular form and can be conveniently used to compute kerma in water. The contributions of several physical processes, such as Compton scattering and pair-production to electron spectra, are separately tabulated. The results are compared with those of Todo et al. (1982) for the single interactions of monoenergetic photons. It is found that the inclusion of processes such as multiple Compton scattering, bremsstrahlung production, positron annihilation in flight, Mohiller and Bhabha scattering from electrons and Moliere multiple scattering from atomic nuclei make a considerable difference in the inferred electron spectrum in water. PMID- 2925390 TI - Influence of organs in the ICRP's remainder on effective dose equivalent computed for diagnostic radiation exposures. AB - The ICRP effective dose equivalent has been compared with a weighted dose equivalent, computed by treating the entire remainder instead of the sample of five remainder organs in the ICRP method as uniformly radiosensitive, for dose distributions from three common diagnostic exposures: chest, dental full-mouth and dental panoramic. Complete dose distributions were computed by a Monte Carlo model. In all three cases the effective dose equivalent was greater than the weighted dose equivalent. The difference was only 20% for the chest exam but was more than fivefold for both dental exposures. Dose distributions for the dental exposures were less homogeneous than for the chest examination. Selection of organs to be included in the remainder markedly affects the effective dose equivalent. In the case of highly inhomogeneous dose distributions, the effective dose equivalent probably significantly over-estimates radiation detriment. PMID- 2925391 TI - Evaluation of reproductive function of female rats exposed to radiofrequency fields (27.12 MHz) near a shortwave diathermy device. AB - In recent years, there has been increased concern regarding effects of operator exposure to the electromagnetic (EM) field associated with shortwave diathermy devices. The present study was designed to investigate the effects, on rats, of repeated exposure to such an EM field. Following repeated exposure for 5 wk, a reduction in fertility occurred as indicated by a reduced number of matings in exposed rats compared to sham-irradiated rats and a reduction in the number of rats that conceived after mating. The data suggest that female operators could experience reduced fertility, if they remained close to the console for prolonged periods. This has particular significant for the physiotherapy profession. PMID- 2925392 TI - Is ionizing radiation regulated more stringently than chemical carcinogens? PMID- 2925393 TI - Order of magnitude absorbed dose reductions in cephalometric radiography. PMID- 2925394 TI - Thallium-201 in human milk: observations and radiological consequences. PMID- 2925395 TI - Effect of smear method on detection of 99mTc radiopharmaceuticals. PMID- 2925396 TI - Preparation and performance of a CaSO4:Dy, Tm thermoluminescent phosphor for long term gamma measurements. PMID- 2925397 TI - Improved cassette recording of multichannel analyzer data. AB - As part of a field experiment, five of these modified tape decks with associated MCAs have been operating successfully for several months in an essentially unattended mode. In addition, this automatic system facilitates readout during attended operation by eliminating the need to press keys. Tapes generated on these decks are totally compatible and interchangeable with those made by the manual cassette unit. PMID- 2925399 TI - A plea for sensible film badge placement in diagnostic radiology. PMID- 2925398 TI - Personnel monitoring in diagnostic radiology: revisited--again! PMID- 2925400 TI - EDE for exposure with protective aprons. PMID- 2925401 TI - Use of effective dose equivalent for external radiation exposures. PMID- 2925402 TI - Recommendations for radioactive waste reduction in biomedical/academic institutions. PMID- 2925403 TI - NRC, NCRP, ICRP and recommendations on prenatal radiation exposure. PMID- 2925404 TI - Care and management of twins. AB - This is a study of the maternal care of 84 sets of twins in their own homes in Sheffield, compared with random and matched singleton controls funded by the Foundation for the Study of Infant Deaths. The findings suggest that the stress experienced by parents appears to be related more to the number of children to be cared for than the fact of twinning. The study revealed that twin babies received more health visitor care and less GP care than singleton babies. PMID- 2925405 TI - Innovation in health visiting. AB - Innovation in health visiting practice is compared to that in the steel and wool industries. The health visiting role is seen as one demanding change and innovation, while health visitors apparently do not see themselves as innovative. Examples of innovation and barriers to innovation are described. PMID- 2925406 TI - Child rearing among Jamaican families in Britain. AB - A study of ten families of Jamaican descent in Britain illustrates variations in child rearing practices dependent on social class, parental country of birth and Rastafarian belief. PMID- 2925407 TI - The behaviour of nine-month and two-year olds as assessed by health visitors and parents. AB - A behaviour checklist for use by health visitors at nine month and two year child development screening is described. Geographical prevalence of difficult behaviours within the health district is examined and comparison made between professional and parental understanding of such difficult behaviours. PMID- 2925408 TI - Health visitors' perceptions of normal infant behaviour. AB - A survey of 50 health visitors revealed a wide range of views on the frequency of certain behaviour patterns associated with feeding, sleeping and crying in babies. The implications of this for health visitor training and client contact are discussed. PMID- 2925409 TI - Passage to Patna. PMID- 2925410 TI - Hailsham Mums' Newsline. PMID- 2925411 TI - Know your organisations. Exploring parenthood. PMID- 2925412 TI - Ageing well in Thetford. PMID- 2925413 TI - Clinical neurologic assessment tool: development and testing of an instrument to index neurologic status. AB - The clinical neurologic assessment tool (CNA) is a 21-item instrument assessing response to verbal and tactile stimulation, ability to follow commands, muscle tone, body position, movement, chewing, and yawning in the patient with head trauma. The CNA was developed to detect subtle changes in the patients' neurologic status that may indicate transitions in the comatose state. The CNA has been extensively pilot tested. Reliability determined by using Cronbach's alpha revealed an internal consistency of 0.96. Concurrent validity testing with the Glasgow Coma Scale indicated a strong positive correlation, r = 0.94. Construct validity was assessed with factor analysis using 0.50 for a loading criterion. Three factors were demonstrated: general level of consciousness, muscle tone and resistance, and chewing or yawning. Discriminant function analysis revealed that the CNA scores correctly classified 95.1% of the patient observations into their respective Glasgow Coma Scale categories. The CNA is reliable, valid, convenient, and easily scored and captures the subtle changes in the patient with head trauma. PMID- 2925414 TI - Person-centered counseling: application in an intensive care setting. AB - Nursing care in an intensive care unit focuses, quite appropriately, on the patient's physical condition. However, the patient has emotional concerns, fears, and anxieties while we are busy attending to his or her physical needs. How can we blend high-technology physical care with the emotional care that patients and their families require? Person-centered counseling is one theoretic model that can be used to achieve this balance. PMID- 2925415 TI - Affectional touch in critical care nursing: a descriptive study. AB - The purpose of this study was to describe selected qualitative and quantitative factors present in nursing situations involving affectional touch. Natural field observation of 30 nurse-patient dyads in three hospital critical care units yielded frequency data in four categories: form of affectional touch, Weiss' qualitative factors, accompaniments, and stimulus. Frequencies of affectional touch and of proximity without touch were also obtained. Modal instances of affectional touch in a 1-hour period were 2, with a range of 0 to 17. Form of affectional touch most frequently used was sustained stationary, with stroking least frequent. The majority of instances of affectional touch were of short duration and low intensity, with visible reaction indicating comfort in approximately two thirds of the instances. Almost three fourths of the instances were accompanied by visual regard and two thirds by vocalization. Patient stimulus before affectional touch was indirect in 52% of the instances and unidentified in another 32%. This study provides clear evidence that, although the use of touch as a nursing comfort measure is widely advocated, affectional touch is infrequent. These results provide information useful to the further development of prescriptive theory for affectional touch in nursing practice situations. PMID- 2925416 TI - Biographic limits to life-extending technology. PMID- 2925417 TI - The senescent heart. AB - There are changes in the elderly population that make them more vulnerable to disease, react differently to disease, and respond differently to drugs. The changes that occur in the geriatric population are (1) general physical deconditioning, (2) blunted physiologic response to change, (3) decreased resilience, and (4) degenerative changes common to aging. Appreciation of these changes helps in the diagnoses, management, and evaluation of prognosis in the senescent patient. PMID- 2925418 TI - Atrioventricular (AV) block induced by a single ventricular extrasystole. PMID- 2925419 TI - Legislation to legalize active euthanasia. PMID- 2925420 TI - Stress ulceration: a serious complication in critically ill patients. PMID- 2925421 TI - Information currently available to the nurse. PMID- 2925422 TI - Efficient allocation of resources: support services, systems, and personnel. PMID- 2925423 TI - Retirement planning options under the new tax law. PMID- 2925424 TI - Measurable patient outcomes: putting theory into practice. PMID- 2925425 TI - Ethical dilemmas in home care of chronically ill elderly persons. PMID- 2925427 TI - Images. PMID- 2925426 TI - Oncology alert for the home care nurse: syndrome of inappropriate antidiuretic hormone. PMID- 2925428 TI - Holistic approach to healing: Part II. PMID- 2925429 TI - Aerosol therapy: a nurse's guide (continuing education credit). PMID- 2925430 TI - Elder abuse: the next step. PMID- 2925432 TI - D-time: a personal reflection. PMID- 2925431 TI - Priorities. PMID- 2925433 TI - Dealing with the elderly alcoholic patient. PMID- 2925434 TI - Alzheimer's disease: the roles of the home health nurse and the caregiver. AB - A family's discomfort or inability to deal with nearly unmanageable situations involved with the home-based Alzheimer's patient can negatively influence the care given. Here the home health nurse's role as educator becomes paramount. PMID- 2925435 TI - The impact of Alzheimer's disease on family caregivers. AB - An understanding of the concerns and fears of caregivers of Alzheimer patients can help the health care professional provide home care management more effectively. PMID- 2925436 TI - Home management of the patient with Alzheimer's disease. AB - Quality long-term management of the Alzheimer's patient requires familiarity with the characteristic stages of the disease, knowledge of appropriate care as the disease progresses, and awareness of the help available from community resources. PMID- 2925437 TI - Incontinence aids for home use. AB - Specific knowledge of the relative merits and costs of equipment and techniques will enable individualized incontinence management for greater patient comfort. PMID- 2925438 TI - Applying the principles of organizational psychology to improve the selection of home health aides and homemakers: Part I. AB - The authors present an employment selection system specifically developed for the home health care industry that is designed to maximize the quality of care by providing capable, committed caregivers to clients. PMID- 2925439 TI - Survival in a nursing shortage. PMID- 2925440 TI - Caregiver grief. PMID- 2925441 TI - Mental status questionnaire. PMID- 2925442 TI - The loss of self. PMID- 2925443 TI - The patient with Alzheimer's disease: retaining the right to make medical treatment decisions. PMID- 2925444 TI - Distribution of glycoconjugates on the plasma membrane and on membranes of the open-canalicular system in human platelets. A cytochemical study. AB - Distribution of carbohydrate moieties in the membrane system of the human blood platelet was studied by electron microscopy employing lectins as a probe. Glutaraldehyde-fixed platelets were treated with biotinylated-lectins (ConA, RCA, WGA, PNA, SBA, DBA and UEA-1) and labeled with horseradish peroxidase-conjugated avidin. Among the lectins used, ConA bound uniformly to the plasma membrane as well as to the membrane of the open-canalicular system (OCS). Other lectins showed more or less reduced binding on the OCS membrane compared with that on the plasma membrane, indicating that there exist regional differences in the distribution pattern of glycoconjugates in the membrane system of the platelet. The relationship of the distribution pattern of the glycoconjugates with the distribution of the major platelet glycoproteins GPIb and GPIIbIIIa is discussed. PMID- 2925445 TI - Localization of calmodulin positive immunoreactivity in the surface epidermis of the brown trout, Salmo trutta. AB - Calmodulin is a Ca2+-dependent modulatory protein which is required in the general regulation of a large number of key processes of cellular metabolism. In the present study, the localization of calmodulin positive immunoreactivity in the epidermis of the brown trout, Salmo trutta was investigated using a specific mouse monoclonal antibody to calmodulin of IgG2 class. The immunoreaction was found only in the superficial epithelial cells that constitute the main histological site for the production of calmodulin positive substances. Because of its distribution, this protein might have a physiological significance in the activation of the microvillar skeleton and in the control of the permeability of the skin epithelium. PMID- 2925446 TI - Coexistence of catecholamine and methionine enkephalin-Arg6-Gly7-Leu8 in neurons of the rat ventrolateral medulla oblongata. Application of combined peptide immunocytochemistry and histofluorescence method in the same vibratome section. AB - An overlapping distribution of catecholamine-containing cells and proenkephaline A derived peptide-containing neurons have been identified in the rat medulla oblongata. However, it is not evident whether the coexistence of these bioactive substances occurs in the same neurons or not. Therefore, we examined the coexistence of catecholamine and methionine-enkephalin-Arg6-Gly7-Leu8 (MEAGL), a proenkephaline-A derived peptide, using a combination of histofluorescence and peroxidase-anti-peroxidase (PAP) immunohistochemical (modified formaldehyde glutalaldehyde (Faglu)) methods on the same tissue sections. We found one third of A1/C1 catecholamine fluorescent cells show MEAGL-like immunoreactivity. PMID- 2925447 TI - Immunocytochemistry of 5-bromo-2'-deoxyuridine labelled oligonucleotide probes. A novel technique for in situ hybridization. AB - A synthetic oligonucleotide probe, complementary to oxytocin m-RNA was labelled enzymatically with 5-bromo-2'-deoxyuridine (5-BrdU) and with [gamma-32P]-ATP. The labelled probes were used for in situ hybridization of histological sections of the mouse hypothalamus. A monoclonal antibody to 5-BrdU and the streptavidine peroxidase technique were used in order to visualize hybridization with the 5 BrdU labelled probe. In situ hybridization with [32P] labelling was detected autoradiographically. With both methods hybridized neurons were visible in the magnocellular hypothalamic nuclei. While immunostaining and radio-labelling provided similar localization of oxytocin m-RNA, only the immunocytochemical technique showed clear cellular resolution of the reaction product. In situ hybridization with 5-BrdU labelled probes followed by 5-brdU immunocytochemistry seems to be a powerful alternative to common autoradiographic techniques. PMID- 2925448 TI - Distribution of lectin binding glycoprotein in osteoclasts. AB - Arachis hypogaea (PNA) lectin, specific for Gal-B-1,3-GalNac disaccharide and Wheat germ (WGA) lectin, specific for (GlcNac) and terminal neuraminic acid were used to identify histiocytic giant cells, osteoclast like giant cells and osteoclasts. PNA lectin, without neuraminidase predigestion was not bound by the giant cells, while they showed a strong reaction with WGA lectin. Neuraminidase pretreatment decreased WGA lectin binding, which supports that neuraminic acid plays a role in the binding of WGA. On the other hand, neuraminidase digestion liberated large amounts of PNA binding sites in every type of giant cells examined, showing a strong, intracytoplasmic granular staining. This observation is indicative of presence of PNA binding sites masked by neuraminic acid. Instead of the intracytoplasmic PNA binding in some osteoclasts a well defined part of the cytomembrane was heavily stained. We suppose that this PNA binding part of cytomembrane equals to the zone of resorption, characterized by the ruffled border of osteoclasts. Our findings indicate that a neuraminic acid substituted PNA binding glycoprotein is synthetized both in osteoclasts and histiocytic giant cells which may indicate a common origin of these cell types. PMID- 2925450 TI - Ultrastructural localization of dentine phosphoprotein in rat tooth germs by immunogold staining. AB - Dentine phosphoprotein (DPP) was localized on thin frozen sections of fixed rat tooth germs by indirect immunogold staining. Antisera were directed against DPP and against glutaraldehyde-treated DPP and were characterized by immuno electroblotting. In odontoblasts, DPP was found to be localized in the cisternae of the rough endoplasmic reticulum (RER) and the Golgi apparatus and in Golgi associated vesicles. Odontoblastic processes were moderately positive for DPP and dentine was intensely labeled on frozen sections of unfixed tissue. Predentine showed a slight immunoreactivity. These results indicate the synthesis of DPP in the RER, its accumulation in the Golgi apparatus and its vesicular transport and secretion via the odontoblastic processes into dentine. The close association of the gold particles with the dentinal collagen fibres makes a role of DPP in linking mineral to collagen conceivable. Matrix vesicles were negative for DPP, suggesting that the protein is not present at the sites of matrix vesicle associated nucleation. PMID- 2925449 TI - Glycoconjugate with terminal galactose. A selective property of macrophages in developing rat lung. AB - Pulmonary macrophages in pre- and postnatal rats were examined histochemically with a battery of peroxidase labeled lectins. Among them, Griffonia simplicifolia agglutinin I-B4 (GSA I-B4) which binds specifically to terminal alpha-galactose showed selective affinity in lung for the monocyte-macrophage line. These cells were demonstrable with GSA I-B4 from the 14th day of gestation through the adult. Extension to the ultrastructural level showed strong selective binding of this lectin to the surface of the plasmalemma and inner face of membranes limiting phagosomes in macrophages. At day 14 of gestation, monocyte-like cells positive with GSA I-B4 were scattered in various organs including lung. The lectin reactive cells in lung increased in number and size with development, infiltrating the interstitium through day 20 of gestation and then also entering the alveolar space. These findings suggest that GSA I-B4 recognizes a surface glycoconjugate characteristic of the pulmonary monocyte-macrophage line. Such selective lectin affinity offers a marker for detecting the pulmonary macrophages and examining their kinetics by light and electron microscopy. PMID- 2925451 TI - A simple fixation procedure for immunofluorescent detection of different cytoskeletal components within the same cell. AB - In recent studies on the cytoskeletal organization of T51B rat liver cells by indirect immunofluorescence microscopy, we have been unable to achieve double staining of microtubules and intermediate filaments within the same cell. In acetone-fixed cells, microtubules were poorly preserved, and two out of three monoclonal antibodies tested did not stain them properly. In formaldehyde-fixed cells, the monoclonal anti-cytokeratin produced an incomplete staining pattern against a diffuse background. We have now developed a fixation protocol which includes simultaneous fixation and extraction with formaldehyde and nonionic detergent in the present of microtubule stabilization buffer. Although developed for a specific purpose, it is of general application as it yields excellent preservation of all cytoskeletal components tested so far, without masking antigenic determinants. The procedure is both simple and fast and will, therefore, be valuable for efficient processing of samples from large-scale experiments, such as the screening for cytoskeletal changes during longterm treatment of cells with drugs or carcinogens. PMID- 2925452 TI - Inhibition by leupeptin and antipain of the intracellular proteolysis of Ii. AB - Intracellular cleavage of Ii was evaluated in immunoprecipitates of radiolabeled Raji cells treated with protease inhibitors (leupeptin, antipain, chymostatin, and pepstatin) or blockers of endosomal function (chloroquine and monensin). Immunoprecipitates with anti-class II and anti-Ii(12-28) sera and VIC-Y1 MoAb revealed Ii cleavage products of 21,000 and 10,000 daltons (p21 and p10) only in leupeptin- and antipain-treated cells. Both p21 and p10 were judged to be N terminal products because they were recognized with anti-Ii(12-28) and not with anti-Ii(183-193) or anti-Ii(192-211) sera. p10 might be derived from p21 because its intensity was increased in inverse proportion to p21 as a function of leupeptin or antipain concentration. p21, but not p10, was recognized by anti class II antibody and thus might originate from class II-associated Ii. In pulse chase studies, p21 and p10 appeared at 2 hr and later after Ii synthesis. p25, an Ii C-terminal fragment, was about 60% reduced by leupeptin or antipain. Intracellular proteolytic cleavage of class II-associated Ii appeared to follow two pathways leading either to N-terminal p21 and p10 or to C-terminal p25. Such cleavages might regulate or catalyze foreign antigen binding to class II. PMID- 2925453 TI - Immunocytochemical characterization of the unusual large granular lymphocytes in human endometrium throughout the menstrual cycle. AB - Leukocyte populations were studied at all stages of the menstrual cycle using a panel of monoclonal antibodies to natural killer cells, T cells, B cells, and macrophages on frozen sections of endometrium. At the time of implantation (mid secretory phase) the majority of leukocytes appear to be Leu19+, CD16-, Leu7-, CD2+, CD3-, CD5-, CD7-, and HLA DR- with the morphology of large granular lymphocytes. The numbers of these cells showed a marked increase in the mid secretory phase. These cells exhibited similar phenotypic characteristics to those found in decidua. These findings, therefore, suggest that the recruitment of these large granular lymphocytes to the uterus is under hormonal control and is not a local response to the presence of invading trophoblast. PMID- 2925454 TI - Mitogen-induced human IgG subclass expression. II. IgG1 and IgG3 subclasses are preferentially stimulated by a combination of Staphylococcus aureus Cowan I and pokeweed mitogen. AB - Mitogens generally stimulate human IgG subclass production in amounts proportional to their abundance in serum (IgG1 greater than IgG2 greater than IgG3 greater than IgG4). We report here that a combination of Staphylococcus aureus Cowan strain I and pokeweed mitogen consistently stimulates human peripheral blood lymphocytes in vitro to preferentially produce more IgG1 and IgG3 than IgG2. This preferential stimulation can be measured by increases in the number of immunoblasts (cells with detectable cytoplasmic immunoglobulin) as well as in secreted immunoglobulin. The preferential stimulation pattern is established by the fourth day of culture and is maintained at least until the tenth day. Removal of T cells and subsequent stimulation of B cells with S. aureus Cowan I and interleukin 1 (IL-1) interleukin 2 (IL-2), interleukin 4 (IL 4), or interferon-gamma (IFN-gamma) failed to enhance any IgG subclass production, indicating the requirement for multiple lymphokines in IgG subclass production. The significance of these findings is discussed with respect to B cell regulatory molecules and the coordinate expression of IgG subclasses. PMID- 2925455 TI - Rare in the US, the human T-lymphotropic virus type I (HTLV-I) was recently found in 10 out of 40,000 donors in this country. PMID- 2925456 TI - A single prophylactic dose of ceftriaxone as total antibiotic therapy in transurethral surgery. AB - Ceftriaxone (1 g, intravenous administration, 30 to 60 minutes preoperatively) was the only antimicrobial therapy used for 103 male patients undergoing transurethral surgery. Only patients who had sterile urine were included in the study. Patients with a preoperative catheter placed were excluded. One transurethral incision of the prostate, four direct-vision internal urethrotomies, and 98 transurethral resections of the prostate were performed. Urine specimens for culture were obtained preoperatively and on first voiding after catheter removal for all patients. During the first postoperative visit (11 to 40 days after surgery), urinalysis was performed for all patients, and specimens for culture were obtained from 89 patients. No infections were noted on cultures of first voided specimens after catheter removal; there were four infections (3.88%) on first postoperative visit cultures. No significant morbidity occurred secondary to urinary tract infection. According to these findings, the use of antimicrobial agents beyond the preoperative and immediate postoperative period in uninfected patients undergoing transurethral surgery does not appear to be indicated. PMID- 2925457 TI - Naloxone alteration of blood flow in a nonischemic region of the partially ischemic gerbil brain. AB - The effect of naloxone (NAL) treatment on cerebral blood flow in the partially ischemic gerbil brain was investigated. Under pentobarbital anesthesia, the right carotid artery in female gerbils was cannulated. A permanent ischemia was produced in the right anterior brain portion by carotid ligation. One hour after the surgical procedure, radioactive 51Cr, microspheres were injected via the carotid catheter before intraperitoneal administration of NAL (50 mg/kg) in saline solution. Five minutes later, radioactive 46Sc microspheres were injected via the carotid catheter. Controls were injected in the same manner with vehicle and microspheres. Brain quarters were assessed for 51Cr and 46Sc radioactivity with a gamma counter. A significant decrease in microsphere deposition was observed with NAL treatment in the right rear, nonischemic part of the brain. No changes in radioactivity were detected in the ischemic portion. These findings suggest that NAL may alter brain blood flow independently of ischemia. PMID- 2925458 TI - Diagnosis and management of ventricular dysphonia. AB - Ventricular phonation may develop on a functional level, or it may occur as an alternative voice for the patient who has an organic disease of the true vocal folds. Three cases that represent iatrogenic, traumatic, and neurologic forms of the disorder are reported. Diagnosis, treatment, and guidelines for follow-up speech therapy are discussed. PMID- 2925459 TI - Subcutaneous emphysema and pneumomediastinum complicating labor in a twin pregnancy. AB - Although a rare complication of labor, subcutaneous emphysema and pneumomediastinum (Hamman's syndrome) must be considered in the parturient complaining of chest or neck pain, dysphagia, or shortness of breath. With conservative management, the prognosis is favorable. The case presented is the first of Hamman's syndrome complicating the labor of a twin gestation. The pathophysiology, symptoms, and management guidelines for the syndrome are reviewed. PMID- 2925461 TI - Lupus: the 'wolf bite' that may be more than skin deep. PMID- 2925460 TI - Facial nerve palsy secondary to acute otitis media. AB - Acute otitis media is diagnosed commonly in the pediatric population. Numerous complications, one of which is facial palsy, may result. Facial paralysis may be the initial complaint in the child in whom acute otitis media later develops on the affected side, as was true in the case reported here. Dehiscence of the fallopian canal, physiologic canaliculi along the facial nerve to the periphery, and host resistance play an integral part in the development of facial nerve palsy from acute otitis media. The two most effective neurodiagnostic studies are the nerve excitability test and electromyography. The author also recommends daily acoustic reflex testing for denervation or reinnervation. Specific indications for conservative therapy (myringotomy, antibiotic, and decongestant) as well as for surgical intervention are discussed. The treatment in the present case was particularly conservative. It included only a broad-spectrum antibiotic, with good results. PMID- 2925463 TI - The contingent negative variation in a Go/No Go avoidance task: relationships with personality and subjective state. AB - Howard et al. (1982) reported an association in mentally abnormal offenders between psychometric impulsiveness and the degree of differentiation in the contingent negative variation (CNV) recorded at the vertex between Go and No Go conditions in a Go/No Go signalled avoidance task. The present study aimed to investigate whether this finding extended to two samples of young, healthy volunteers using a variety of impulsiveness-related measures. As well as examining the Go/No Go CNV recorded from the vertex, the present study investigated the Go/No Go CNV recorded bilaterally at central (C3 and C4: Experiment 1) and temporal (T3 and T4: Experiment 2) electrode derivations. The study also investigated relationships between the Go/No Go CNV and subjective state. including stress and arousal as measured by a mood-adjective checklist, as well as several task-related state measures. The Go CNV recorded at the vertex was found to relate to a variety of impulsiveness-related measures, in particular to Eysenck's Impulsivity, Venturesomeness and Psychoticism. The Go/No Go CNV recorded at temporal sites was more closely related to measures of Emotionality. While the Go CNV appears to be an electrocortical index of a neuropsychological system mediating subjective stress, the No Go CNV appears to index subjective arousal. Results are interpreted in terms of orthogonal 'primary' and 'secondary' appraisal processes (Folkman et al., 1979), and their implications for Gray's (1982) neuropsychological theory of anxiety and Tucker and Williamson's (1984) neural control systems model of human self-regulation are outlined. PMID- 2925462 TI - Human Pavlovian HR-decelerative conditioning with negative tilt as US: evidence of vagal and sympathetic influences on the UR in dogs. AB - Following a review of studies employing negative tilt in human Pavlovian conditioning of heart rate (HR) deceleration (Furedy et al, in press), this paper reports data based on animal subjects on such physiological aspects of the decelerative unconditioned response (UR) as the degree of vagal involvement. Five anesthetized dogs underwent 90 degrees negative body tilts pre- and postbilateral vagotomy, while interbeat interval (IBI), left ventricular pressure (LVP) and its first derivative, d(LVP)/dt, which is a measure of sympathetic cardiac drive, were recorded. Consistent with the vagal interpretation of the tilt-induced decelerative UR, the results indicated that vagotomy markedly changed the tilt induced bradycardic reflex from a fast-recruiting, large-magnitude (over 45%), and sustained (throughout the 20-27-s tilt) IBI increase, to slower-recruiting, and markedly smaller (less than 5%) IBI increase. However, there was also evidence of an initial sympathetic excitation of about 5 s, as indicated by a 45% increase in d(LVP)/dt, which returned to baseline level by 9 s following tilt onset. Vagotomy increased this tilt-induced sympathetic excitation to about 100%, and it remained at above 70% throughout the tilt. Prevagotomy LVP showed a slight (about 10%) and delayed (about 6 s following tilt onset) depressor response, which was eliminated by vagotomy. Finally, unaveraged data from individual dogs suggested that prevagotomy, LVP changes preceded IBI changes. Regarding implications of these results for human HR deceleration-inducing preparations, we conclude that the different physiological mechanisms that accompany and/or produce a given change in HR need continuing investigation with multiple dependent physiological variables (which are assessed for topographical differences), and in both human and animal preparations. PMID- 2925464 TI - Alpha reactivity in schizophrenia and in schizophrenic spectrum disorders: demographic, clinical and hemispheric assessment. AB - Alpha EEG reactivity was assessed in a carefully diagnosed sample of 84 schizophrenic and schizophrenic spectrum disorder patients, both under resting conditions (eyes closed and eyes open) and during two spatial-geometric cognitive tasks. The influence of the subject's demographic (sex and age), clinical (diagnostic subtypes, disease course, CT scan characteristics) and neurophysiological (hemispheric recording and different cognitive tasks) characteristics on alpha peak reactivity was analyzed by means of multivariate analysis of variance. The results indicated a significant effect of type of illness on alpha EEG reactivity, patients with a diagnosis of undifferentiated and disorganized schizophrenia having the lowest alpha reactivity levels. None of the other variables considered had any contributing effect. The results are discussed in terms of orienting responses and hemispheric CNS organization in functional psychoses. PMID- 2925465 TI - Repeated acoustic stimulation of acute schizophrenic patients and the habituation of EEG power changes. AB - Habituation in psychiatric patients to repeated stimuli has typically been described in connection with the measurement of the skin conductance orienting response. Here EEG power spectra of acute schizophrenic patients and normals to 4 trials of an acoustic stimulation were examined for evidence of habituation. In response to stimulation the alpha EEG reactivity was less distinct in schizophrenics than in normals. This is in agreement with the theory of hypovariability or hyperstability of the EEG in schizophrenics. Signs of habituation in acute schizophrenics were clearer in fast beta frequencies of the parietal leads. PMID- 2925466 TI - Electrodermally differentiated subgroups of anxiety patients and controls. II: Relationships with auditory, somatosensory and pain thresholds, agoraphobic fear, depression and cerebral laterality. AB - Patients diagnosed (DSM III) with anxiety disorders (agoraphobia, panic syndrome, generalised anxiety syndrome) were classified along with controls as electrodermally stabile or labile on the basis of non-specific electrodermal activity and rate of habituation to tones. While patients showed more evidence of psychopathology than controls on scales of anxiety, neuroticism, depression and agoraphobic fear, patient labiles scored higher than stabiles on agoraphobic fear and were differentiated by higher scores of Beck depression. They were also more sensitive to pain, whereas patient stabiles were less sensitive at absolute somatosensory threshold. Amongst controls agoraphobic fear was associated with lability and stabiles scored higher on autonomy in locus of control. Lateral asymmetries in auditory thresholds were consistent with reciprocal hemispheric influences on electrodermal reactivity and habituation, modifiable by anxiety. Interrelationships between fear, depression, sensitivity to somatosensory stimulation, pain, and superior vigilance performance in patient labiles were consistent with elevated right hemisphere function. PMID- 2925467 TI - Basal adrenocortical activity and DST in electrodermally differentiated subgroups of panic patients. AB - Twenty nine patients with panic disorder or agoraphobia with panic attacks were studied. The relationship between pre- and postdexamethasone serum cortisol level and electrodermal lability as reflected in electrodermal habituation rate and resting non-specific electrodermal activity was investigated. The frequency of non-suppression of cortisol following dexamethasone (DST non-suppressors) (at 5 micrograms/dl cut-off level) was 29.6% for the total group of patients. The basal plasma cortisol concentration showed positive correlation with the electrodermal habituation rate. The basal plasma cortisol level of slow habituator panic patients was significantly higher compared to rapid habituator patients, and it was above the normal range. On the contrary in rapid habituator panic patients the pre- and postdexamethasone cortisol difference was significantly less than in slow habituator patients, due to the normal basal plasma cortisol level and the relatively reduced rate of feedback suppression of cortisol following dexamethasone. Of the rapid habituator panic patients, 50% were non-suppressors following dexamethasone (at 5 micrograms/dl cut-off level). The above results might reflect two relatively different patterns of hypothalamic-pituitary-adrenal dysregulation in connection with two extremes of electrodermal habituation rate in panic patients. PMID- 2925468 TI - 40-Hz EEG asymmetry during recall of emotional events in waking and hypnosis: differences between low and high hypnotizables. AB - Sixteen high and thirteen low hypnotizable women, who had participated in our previous study (De Pascalis et al., 1987), were enrolled in a hypnotic session. After the hypnotic induction they were requested to recollect 2 positive and 2 negative personal life experiences. In our previous study subjects performed similar tasks in a waking-state. Hypnotizability was evaluated the first time with the Harvard Group Scale of Hypnotic Susceptibility (Form A) and, a second time, individually, with the Stanford Hypnotic Susceptibility Scale (Form C). The State Trait Anxiety Inventory, Maudsley Personality Inventory, and Tellegen Absorption Scale were administered. Upper-trapezius electromyogram (EMG) and bilateral electroencephalogram (EEG) activities within the 35-45 Hz band were recorded. Self-report rating scores for vividness of visual imagery and emotional feeling of the material recalled were evaluated. The 40-Hz EMG amplitude and the left and right hemisphere 40-Hz EEG densities were obtained. The data collected in hypnosis were compared with those in the waking-state. High hypnotizables, with respect to the lows, displayed significantly lower 40-Hz EEG density in the rest condition. High hypnotizables, while they were in hypnosis, showed an increase of 40-Hz EEG density during emotional recall compared with rest periods. In contrast, low hypnotizables, after hypnotic induction, showed no density change during tasks compared to the rest conditions. Different hemispheric trends were found between groups. Highs showed an increase of 40-Hz EEG density over both hemisphere during positive emotions and a density increase in the right and a density reduction in the left during negative ones. This hemispheric trend was found in waking and hypnotic conditions although in the hypnotic condition more pronounced hemispheric patterns were observed. The Tellegen Absorption Scale was found positively related to hypnotizability and with the level of 40-Hz density increase on the right hemisphere during emotional tasks. High hypnotizables, with respect to the lows, were able to access affects more readily. They also showed a greater hemispheric specificity in waking and hypnotic conditions. PMID- 2925469 TI - Compliance with breast self-examination instruction in healthy adolescents. AB - Compliance with breast self-examination was prospectively assessed in three groups of healthy outpatient adolescents 6 weeks, 3 months, and 6 months after instruction. Although 87%, 59%, and 71% of the three respective groups reported sporadic practice of breast self-examination, only 39%, 9%, and 18%, respectively, performed the procedure timed correctly with the menstrual cycle. Those adolescents tested at 6 weeks demonstrated a high degree of proficiency in replicating the procedure on a silicone model. There was no significant difference between demographic variables or personal health beliefs regarding breast cancer and breast self-examination compliance. Our findings suggest that adolescents can effectively perform breast self-examination, but their practice is erratic. Thus, we recommend that when instruction in breast self-examination is given, the examination schedule should be reinformed at a follow-up visit. PMID- 2925471 TI - Alcohol and vehicular injuries in adolescents. AB - Although there is a disproportionately high accident rate among adolescent drivers due to inexperience, alcohol appears to play a significant role in this number one killer for the age group. To assess this, the level of blood alcohol was measured in adolescents admitted to a trauma center following vehicular injuries. PMID- 2925470 TI - Characteristics of males at a public health department contraceptive service. AB - To effectively confront teenage pregnancy, the characteristics, attitudes, and behaviors of males, along with females, need to be better understood. This pilot study examined young males who visited the family planning clinic of a public health department to obtain free condoms. Questionnaires were distributed over a 4-week period. Nearly 30% of males reported having sex 11+ times a month. However, an equal proportion reported having sex three or fewer times in the same interval. Most males reported using condoms during sex, although one quarter reported use as "seldom." The health department was a major source of condoms and was positively evaluated because condoms were free and there were "no questions asked." Only one third of the males reported using another method of contraception. Results suggest a major role of the health department in condom availability and the potential need for contraceptive services for males. PMID- 2925472 TI - Anorexia nervosa. Hospitalization on adolescent medicine units and third-party payments. AB - To determine the appropriateness of hospitalization for patients with anorexia nervosa on an adolescent medicine unit, major and minor criteria justifying admission were developed. Hospitalization was considered necessary when one major and three minor, or six minor, criteria were met. A retrospective review of 20 patient records was conducted and all met the criteria. Eighteen patients were discharged with objective findings of improvement. Two were transferred to a psychiatric unit for prolonged care. A review of the financial records disclosed that four hospitalizations had been contested (partially or in total) by the patients' insurance company. Thus, in 20% of the records meeting the criteria for admission third parties refused to pay. Because insurance company denial may seriously undermine therapy and adversely influence outcome, it is proposed that a category of "Malnutrition Secondary to Anorexia Nervosa" be accepted as reimbursable under medical coverage for acute care treatment in qualified adolescent medicine units. PMID- 2925473 TI - Career satisfaction in adolescent medicine. A survey of physicians trained over a 20-year period. AB - National data are available on the career undertakings of those trained in adolescent medicine, but longitudinal data on actual career and job satisfaction is lacking. Forty-five physicians trained in adolescent medicine from 1965 to 1985 at a large urban teaching hospital were surveyed using the Jewitt/Greenberg Career Satisfaction Questionnaire. Thirty two (71%) responded. Twenty-one (66%) were primarily in practice, eight (25%) were in academic medicine, and three (9%) were involved in administration. Five (16%) had careers in adolescent and/or young adult health care. Thirty-one (97%) claimed to at least "like" their career, and 29 (91%) felt "satisfied." Only three (9%) desired to change their career, but 11 others (34%) stated they would if they could have an equal opportunity in a new career. Four individuals (13%) would not have chosen medicine if given another chance, and 12 (30%) would not have chosen pediatrics. Greatest satisfaction was derived from patient care activities (62%), the actual work site and job (50%), and finances (40%). Dissatisfaction resulted from too little money (34%), inadequate time (25%), administrative problems (22%), and patient-related problems (22%). A large majority (72%) desired to be acknowledged as specialists. This review of graduates from a single program provides a unique perspective on the ultimate careers of trainees. A similar review of other programs may help facilitate teaching and correct programatic deficiencies. This review also suggests that careful thought should be given to a way of properly acknowledging, as specialists, those trained in adolescent medicine. PMID- 2925474 TI - Enuresis following masturbation in a mentally retarded adolescent. AB - An unusual presentation of enuresis is described. A mentally retarded adolescent male with normal bladder function wet his bed while awake following masturbation. Initially, this sequence was not apparent to the parents or physicians. A multidisciplinary approach to the symptom helped to define and focus on the circumstances of the symptom itself, allowing for successful intervention. PMID- 2925475 TI - Limited data on Mexican-American pregnant and nonpregnant teenagers. PMID- 2925476 TI - Recognition of ovulatory/anovulatory cycle pattern in adolescents by mucus self detection. AB - The high frequency of anovulation during adolescence raises the question of whether a method for the recognition of ovulation by self-detection of cervical mucus patterns is useful in teenagers. We performed a secondary analysis of 1049 completely recorded cycles of 235 teen women 15-17 years of age with a gynecologic age from less than 1 to 7 years. These subjects had learned to monitor their fertility patterns using the Billings Ovulation Method. The cycles were analyzed by the length of the mucus and luteal phases and recorded "peak symptom." Ovulatory cycles were grouped by the length of the luteal phase, short (4-8 days) and average (8-18 days), and plotted against gynecologic age. The frequency of anovulatory cycles was comparable to Vollman's age-stratified monophasic cycle groups. Ovulatory patterns were found at gynecologic ages of 1 year, 49%; 2 years, 60%; 3 years, 72%; 4 years, 61%; 5 years, 86%; and 6 years, 71%. The study proved that teen-age women can distinguish patterns of ovulation and anovulation by self-detection of cervical mucus. PMID- 2925478 TI - Corporate practice of veterinary medicine. PMID- 2925477 TI - Birth weight outcomes in a teenage pregnancy case management project. AB - While many comprehensive health care programs for pregnant adolescents are designed to improve the birth weights of the babies born, few provide statistical evidence that they were able to do so. In this study, information was gathered prospectively on 411 mothers in a Teenage Pregnancy and Parenting Program (TAPP) that coordinated medical, educational, and social services through individual case management and agency-level coordination, information on the mothers, their pregnancy, and services received. The low birth weight rate for TAPP participants was significantly lower than the rate for San Francisco teens prior to the establishment of the program (8.1% versus 12.0% p less than 0.05). The mean weights of babies born to teens in TAPP were significantly higher than those in San Francisco after controlling for differences in the race, infant gender, parity, and age (p less than 0.0001). Participation in the TAPP program prior to delivery was more strongly associated with better birth weight outcomes than was race, age, parity, or gender. Participation in the TAPP program was associated with significantly better birth weights independent of receiving a minimal number of prenatal medical visits adequate for the gestational age of the baby at birth. Our results provide evidence of better health outcomes for the babies of teens who had case management that included continuous individual counseling and coordination of health, education, psychosocial, and nutrition services. PMID- 2925479 TI - Videotaping as a potential safeguard against veterinary malpractice lawsuits. PMID- 2925480 TI - ECG of the month. Sinus tachycardia and hyperkalemia in a horse. PMID- 2925482 TI - Arteriosclerosis in a rabbit. AB - Extensive mineralization of the aorta, brachiocephalic trunk, and the left subclavian, both iliac, common carotid, and renal arteries were found at necropsy in a 3-year-old French Lop rabbit. The rabbit had been examined previously for seizures, at which time abdominal radiography revealed calcification of the abdominal aorta and external iliac arteries. Treatment was not initiated, and the rabbit died 4 months later of bacterial pneumonia. The rabbit also had hypercalcemia. In contrast to many species, the blood calcium concentrations of rabbits reflect dietary intake. PMID- 2925481 TI - Randomized efficacy trials of long-acting oxytetracycline in neonatal pigs. AB - Prophylactic efficacy of 100 mg of long-acting oxytetracycline (OTC) given IM to neonatal pigs within 12 hours of birth was evaluated in a swine herd. The herd had a history of increased neonatal mortality, diarrhea, foot abscess, and arthritis in nursing pigs. Two trials were conducted in which liters and individual pigs were the treatment groups of interest. In both trials, OTC treatment failed to reduce mortality, diarrhea, or arthritis or the need for subsequent antimicrobial therapy (P greater than 0.05). Preweaning weight gains were not increased (P greater than 0.05) in treated pigs. However, in the individual pig trial, foot abscess rates were significantly (P = 0.01) lower in treated pigs (3.7%) than in nontreated pigs (8%). Aerobic bacteria isolated from pigs with diarrhea, arthritis, or foot abscess had minimum inhibitory concentrations for OTC greater than or equal to 64 micrograms/ml or were classed as resistant on the basis of disk-diffusion tests. PMID- 2925483 TI - Small-colon rupture attributable to granulosa cell tumor in a mare. AB - A large granulosa cell tumor was believed to be responsible for causing obstruction and subsequent rupture of the small colon in a 10-year-old Quarter Horse mare. Two months earlier, a mass, tentatively diagnosed as granulosa cell tumor of the left ovary, had been identified by means of rectal palpation and ultrasonography. The mare was evaluated for clinical signs of acute, severe, abdominal pain, increased heart rate, cyanotic mucous membranes, clinical dehydration, with high PCV, leukopenia, and extreme abdominal distension. A large soft tissue mass and taut band that constricted the lumen of the small colon were palpable per rectum. Septic peritonitis was diagnosed on the basis of results of abdominocentesis. Exploratory surgery revealed extensive fecal contamination of the abdominal viscera, and the mare was euthanatized because of the resultant poor prognosis. At necropsy, the small colon was occluded by a taut, left broad ligament and the ovarian mass that was proved to be a granulosa cell tumor. The occlusion had caused impaction of the small colon, with subsequent perforation at the level of the broad ligament. PMID- 2925484 TI - Transient, traumatically induced, central diabetes insipidus in a dog. AB - A 9-year-old mixed-breed dog was evaluated for dental malocclusion secondary to mandibular fractures that had been repaired after the dog had been hit by a car. The dog had hypernatremia, high plasma osmolality, low urine osmolality, and hyposthenuria with adequate fluid administration. Skull radiography revealed a fracture line at approximately the level of the pituitary fossa. Administration of exogenous vasopressin resulted in an increase in urine specific gravity and urine osmolality, a decrease in serum osmolality, and a normalization of serum sodium concentrations. Follow-up evaluation revealed a reduction in the frequency of exogenous treatment with vasopressin over the ensuing months, indicating transient, traumatically induced, central diabetes insipidus. PMID- 2925485 TI - Movement disorders during sleep in cats and dogs. AB - Spontaneous sleep movement disorders in 5 cats and 3 dogs were studied. Objective abnormalities during sleep were confirmed by electrographic or behavioral monitoring techniques in all animals. The cause of the disorder was CNS disease in 3 animals. A cause was not discovered in the other 5 animals, although at necropsy, 2 were found to have thyroid tumors. Many pharmacologic treatments were ineffectual, but trials with the benzodiazepine tranquilizer, clonazepam, suggested it will prove useful in controlling violent movements during rapid-eye movement sleep. PMID- 2925486 TI - Pyometra involving uterus masculinus in a cat. AB - A neutered male cat with a history of intermittent antibiotic-responsive fever and strangury had pyometra involving uterus masculinus. The infected structure was removed, and episodes of infection and strangury ceased. PMID- 2925487 TI - Food hypersensitivity in cats: 14 cases (1982-1987) AB - Food hypersensitivity was diagnosed in 14 cats. Clinical signs varied; pruritus (100%), alopecia (64%), and papules (21%) were the ones most commonly observed. Pruritus was localized principally to the head or to the neck or ear region in 42% of the cats. Diagnosis was made on the basis of resolution of clinical signs when cats were fed a restricted ("hypoallergenic") diet, and recurrence of signs when cats were fed their original diet or other food. The most common allergens (on the basis of dietary challenge exposure) were fish and dairy products. Age or sex predilection was not observed, and 9 (64%) of the cats were domestic shorthairs. Owners could not relate the onset of clinical signs with a recent change in diet. Three cats had concurrent flea bite, inhalant, or flea collar hypersensitivity. PMID- 2925488 TI - Treatment and prognostic factors in lymphoma in cats: 103 cases (1977-1981). AB - The records of 103 cats with lymphoma that underwent chemotherapy were reviewed. Diagnosis was confirmed by cytologic or histopathologic examination of appropriate tissue specimens. Sixty-four cats (62%) had a complete response to chemotherapy (median survival time, 7 months); 21 cats (20%) had a partial response (median survival time, 2.5 months); and 18 cats had a minimal response (median survival time, 1.5 months). Seventy-seven cats (75%) died of recurrent or progressive lymphoma, 9 cats died of feline leukemia-related anemia, 13 cats died of unrelated causes, and 4 cats were alive. Stage of disease was significantly (P = 0.009) related to response to treatment, and stage of disease and FeLV status were both significantly (P = 0.002 and P less than 0.001, respectively) related to survival. PMID- 2925489 TI - What is your diagnosis? Multifocal lytic bone disease. PMID- 2925490 TI - Apprehensive about some trends in the profession. PMID- 2925491 TI - Transmission of leishmaniasis. PMID- 2925492 TI - Equine drug use: protecting your license. PMID- 2925493 TI - Medical waste: confusion reigns. PMID- 2925494 TI - Clients beliefs vs veterinary attitudes. PMID- 2925495 TI - Coxiella burnetii infection (Q fever). PMID- 2925496 TI - Impact of trichomoniasis on the cow-calf producer's profitability. AB - Using current knowledge of bovine trichomoniasis, a computer spreadsheet simulation model was developed to contribute to the understanding of the disease dynamics and the disease's impact on calf crop, weaner calf production, and revenue returns. Two disease prevalence simulations were generated with the model. In each simulation, 200 susceptible cows were confined with 5 fertile bulls. In simulation 1, one bull was infected with Tritrichomonas foetus (prevalence, 20%); in simulation 2, 2 bulls were infected (prevalence, 40%). The remaining bulls in these groups were designated noninfected. The disease simulation outcomes for breeding and calving variables were compared with a similar but noninfected model group, simulation 0. The disease model predicted a reduction of 14 to 50% in annual calf crop, a prolonged breeding season, a reduction of 5 to 12% in the suckling/growing period, a reduction of 4 to 10% in pounds of marketable calf crop at weaning, a reduction of 4 to 10% in monetary return per calf born, and a substantial reduction of 5 to 35% in the return per cow confined with a fertile bull. PMID- 2925497 TI - Recurring tetraparesis attributable to a heartworm in the epidural space of a dog. AB - Recurring nonambulatory tetraparesis caused by a heartworm in the epidural space was diagnosed in a dog. On myelography and digital subtraction imaging, the parasite appeared as a large extradural mass. Surgical removal of a mature, female Dirofilaria immitis resulted in resolution of the neurologic signs. PMID- 2925499 TI - Treatment of cataplexy in a dog with narcolepsy. AB - A 1-year-old female Rottweiler with a history of narcolepsy and cataplexy lost weight and became worse when given cholinergic agents and/or prednisolone over a 12-day period. The dog was then treated with imipramine HCl, and has been almost clinically normal for 2 years. PMID- 2925498 TI - Paraparesis caused by epidural granuloma in a cat. AB - Caudal paraparesis in a cat was determined to be caused by an epidural mass. Surgical decompression was performed, and the mass was determined to be a granuloma. Fusobacterium and Bacteroides spp were isolated from the granuloma. Epidural granulomas are seldom reported in dogs and cats. Decompression and administration of antibiotics led to recovery of this cat even though in human beings an unfavorable prognosis is given if neurologic deficits have developed. PMID- 2925500 TI - Reversal of atrial tachycardia with intravenous administration of verapamil in a dog. AB - Intravenous administration of verapamil at low dosage was effective in reversal of atrial tachycardia of unknown origin in a dog. The sinus rhythm remained normal for 24 hours before it reverted back to atrial tachycardia. A second IV administration of verapamil was effective in reversal of the atrial tachycardia, and a tapering dosage of verapamil, PO, was used to maintain normal sinus rhythm. PMID- 2925502 TI - 1987 professional incomes of US veterinarians, by hours worked and years since graduation. PMID- 2925501 TI - Failure of omasal transport attributable to perireticular abscess formation in cattle: 29 cases (1980-1986). AB - During a 7-year period, failure of omasal transport attributable to a perireticular abscess was diagnosed in 29 cows. Affected cattle were examined because of anorexia, hypogalactia, and bilateral abdominal distention. The cows were all female Holsteins, 15 months to 10 years old. The abscess was identified during exploratory celiotomy and rumenotomy or at necropsy. Traumatic reticuloperitonitis was believed to be the cause. Twenty-seven cattle (93%) were treated surgically. The abscess was drained into the reticulum or omasum in 25 cows (86%). Twenty-four cows (83%) survived to the time of discharge from the hospital, and 20 (69%) survived for at least 1 year and became productive members of the herd. This is a better survival rate than that reported for other causes of vagal indigestion. PMID- 2925503 TI - What is your diagnosis? Gastric dilatation; possible diaphragmatic hernia. PMID- 2925504 TI - Summary of the policy goals and strategies. PMID- 2925505 TI - The true issue: meeting service needs for health and medical care. PMID- 2925506 TI - Post conference reflections: autonomy and independence for health professionals? PMID- 2925507 TI - Policy process framework: a systems approach to policy development. AB - This paper discusses a framework for understanding policy analysis and development. The framework presented can be used in the policy development process or post facto in policy analysis. The usefulness of the framework is that it provides a means to think about a policy and its development. It is not prescriptive, nor is it predictive about any particular policy. Policy analysis has tended to rely too heavily on technical analysis, with insufficient attention to other dimensions. This framework offers a basis for people to talk across organizations and cultures. PMID- 2925508 TI - L-671,329, a new antifungal agent. II. Structure determination. AB - Based on spectroscopic data L-671,329, isolated from a filamentous fungus ATCC 20868, has been assigned the structure 1. The compound is a lipopeptide antifungal agent and a structural analog of echinocandin B. PMID- 2925509 TI - New products related to kinamycin from Streptomyces murayamaensis. I. Taxonomy, production, isolation and biological properties. AB - Six new products of Streptomyces murayamaensis sp. nov. Hata et Ohtani, the producer of the kinamycins, were isolated by silica gel column chromatography. The antibacterial activities of the new products, as well as that of dehydrorabelomycin and murayaquinone, previously isolated products of the same organism, were compared to the kinamycins. Three of the products had antibacterial activities similar to the kinamycins, while two others had activity only against Gram-positive bacteria. Dehydrorabelomycin and one other metabolite had no detectable antibacterial activity. The organism was found to be capable of aerial mycelium formation, with sporophores branched at regular intervals bearing square-ended spores with smooth surfaces. The culture contains L,L-diaminopimelic acid in the cell wall (Type I), is highly resistant to lysozyme, and lecithinase- and melanin-positive, suggesting a relationship with the genus Streptoverticillium and the lavendulae group of the genus Streptomyces. PMID- 2925510 TI - New products related to kinamycin from Streptomyces murayamaensis. II. Structures of pre-kinamycin, keto-anhydrokinamycin, and kinamycins E and F. AB - Four new colored components of Streptomyces murayamaensis sp. nov. Hata et Ohtani, the producer of the kinamycins, have been isolated and their structures determined by a combination of mass spectral, high field NMR and biosynthetic techniques. The first compound with the benz[b]carbazole skeleton in the biosynthetic pathway of kinamycin D has been named "pre-kinamycin" (7). A keto epoxide kinamycin intermediate has been labeled "keto-anhydrokinamycin" (9), and the 1'-monoacetate of kinamycin has been called kinamycin E (12). Natural production of deacetylkinamycin (13, now labeled kinamycin F) by S. murayamaensis has been confirmed by an isotope trapping experiment. The role of these new intermediates in kinamycin biosynthesis is discussed. PMID- 2925511 TI - Fosfonochlorin, a new antibiotic with spheroplast forming activity. AB - A new antibiotic, fosfonochlorin, was found in the culture filtrate of four strains of fungi freshly isolated from soil samples. These strains were identified as Fusarium avenaceum, Fusarium oxysporum, Fusarium tricinctum and Talaromyces flavus. Fosfonochlorin was a low molecular weight antibiotic (MW 158), soluble in water and methanol, but insoluble in acetone, ethyl acetate and chloroform. It was named after its possession of phosphorus and chlorine atoms, each one molar in its structure. The structure was determined as chloroacetylphosphonic acid mainly by the 1H NMR and mass spectrometric analyses. It was moderately active against some species of Gram-negative bacteria and its synergistic effect with glucose-6-phosphate was observed on Staphylococcus aureus and Escherichia coli. Spheroplast formation of the susceptible organisms with this antibiotic suggested that it might inhibit their cell wall synthesis. PMID- 2925513 TI - Myrocin C, a new diterpene antitumor antibiotic from Myrothecium verrucaria. II. Physico-chemical properties and structure determination. AB - The structure of a new antitumor antibiotic, myrocin C, from a strain of Myrothecium verrucaria was characterized as a pentacyclic pimarane diterpene composed of a gamma-lactol group and a unique cyclopropane ring on the basis of its physico-chemical properties and spectroscopic data as well as a single crystal X-ray diffraction analysis of its monoacetyl derivative. PMID- 2925512 TI - UK-63,052 complex, new quinomycin antibiotics from Streptomyces braegensis subsp. japonicus; taxonomy, fermentation, isolation, characterisation and antimicrobial activity. AB - UK-63,052 complex, a new group of quinomycin-like antibiotics comprising UK 63,052 (factor A), UK-63,598 (factor C), UK-65,662 (factor B) and several uncharacterised minor components, is produced by a new subspecies of the genus Streptomyces for which the name Streptomyces braegensis Dietz subsp. japonicus, is proposed. The strain, N617-29, is characterised by a negative melanin reaction, grey aerial mycelium, spiral spore chains and smooth or slightly warty spores. Structure determination has identified UK-63,052, C56H68N10O14S2, UK 63,598, C53H62N10O14S2 and UK-65,662, C55H66N10O14S2 as quinaldic acid substituted quinomycins with unusual bridgehead sulfur substitution as shown in Fig. 3. PMID- 2925515 TI - Complestatin, a potent anti-complement substance produced by Streptomyces lavendulae. I. Fermentation, isolation and biological characterization. AB - A new potent inhibitor of complement system, named complestatin, was isolated from the mycelium of Streptomyces lavendulae SANK 60477. Complestatin (C61H45N7O15Cl6, MW 1,325) was a peptide compound having two unusual amino acids, D-(-)-4-hydroxyphenylglycine and D-(-)-3,5-dichloro-4-hydroxyphenylglycine. This compound inhibited the hemolysis of sensitized sheep erythrocytes (EA) mediated by guinea pig and human complement 50% at concentrations of 0.4 and 0.7 micrograms/ml, respectively, but did not trypsin and alpha-chymotrypsin activities at 200 micrograms/ml. When complestatin was administered intravenously to the sensitized guinea pigs, it strongly inhibited the systemic anaphylactic shock elicited by the antigen probably by blocking generation of anaphylatoxins (C3a and C5a). PMID- 2925514 TI - Metabolic products of microorganisms. 252. Isolation of new nikkomycins from Streptomyces tendae. AB - Two new nikkomycins were isolated from the culture broth of Streptomyces tendae Tu 901/PF 53+-3. The new compounds are the dipeptide nikkomycin pseudo-Z (psi Z) and tripeptide nikkomycin pseudo-J (psi J), which are analogues to nikkomycins Z and J. Nikkomycins pseudo-Z and pseudo-J have a C-glycosidic linkage between uracil and 5-amino-5-deoxy-D-allo-furanuronic acid, which is comparable to the C glycosidic bond in pseudouridine. The new Cc-nucleoside nikkomycins exhibit a lower biological activity than the CN-nucleoside nikkomycins. PMID- 2925516 TI - New cirramycin-family antibiotics F-1 and F-2. Selection of producer mutants, fermentation, isolation, structural elucidation and antibacterial activity. AB - Two new 16-membered macrolides, cirramycins F-1 and F-2, were isolated from the culture filtrate of a mutant strain B-1425 of Streptomyces cirratus JTB-3. The antibiotics were also produced by bio-transformation of cirramycin A1 using a blocked mutant strain A-0033. Structures of F-1 and F-2 have been elucidated by spectral interpretation and analysis of acid degradation products. Both involved isomeric modification of a neutral sugar; F-1 contained L-rhodinose, and F-2 L amicetose. Based on spectral data, cirramycin F-1 and antibiotic A6888C were found to be identical. Cirramycins F-1 and F-2 are active against Gram-positive bacteria, but less active than cirramycin A1. PMID- 2925517 TI - Ramoplanin (A-16686), a new glycolipodepsipeptide antibiotic. IV. Complete sequence determination by homonuclear 2D NMR spectroscopy. AB - Homonuclear 2D NMR spectroscopy double quantum filter correlation spectroscopy (DQF-COSY), relayed-COSY, nuclear Overhauser enhancement spectroscopy (NOESY), and DQF-relayed-NOESY) allowed the complete determination of the core depsipeptide of antibiotic ramoplanin (A-16686). In particular, the DQF-relayed NOESY experiments were essential in assigning the single signals close to the diagonal. PMID- 2925518 TI - A new group of antibiotics, hydroxamic acid antimycotic antibiotics. II. The structure of neoenactins NL1 and NL2 and structure-activity relationship. AB - The structures of neoenactins (NEs) NL1 and NL2, novel antimycotic antibiotics produced by Streptoverticillium olivoreticuli in a precursor-oriented fashion, were elucidated by 1H and 13C NMR and mass spectroscopic studies. The structures of both antibiotics are closely related to that of NE-A, the major component of NE congeners, being classified in the group of hydroxamic acid antimycotic antibiotics in which L-serine and a diketo amine form a hydroxamic acid structure. To study the role of the carbonyl groups in the biological activities of the hydroxamic acid antimycotic antibiotics, NE-A was modified by reaction with various carbonyl reagents. In terms of antimycotic activity, the derivatives are classified into two distinct groups; the first ones are fairly comparable to but not exceeding and the second ones are less active than NE-A depending on their tendency to revert to NE-A by hydrolysis. In general, the biological activities of the derivatives are inversely proportional to their stabilities to hydrolysis. PMID- 2925519 TI - Synthesis and antibacterial activity of novel 3-substituted carbacephems. AB - A series of novel 3-heterocyclothio substituted carbacephems having phenylglycyl side chain have been prepared starting from 3-H carbacephem. The compounds exhibit better chemical stability than the corresponding cephalosporin and strong activity against Gram-negative and Gram-positive organisms including Enterococcus faecalis. PMID- 2925520 TI - 9,11-cyclic acetal derivatives of (9S)-9-dihydroerythromycin A. AB - A series of 9,11-cyclic acetal derivatives of (9S)-9-dihydroerythromycin A (4) have been prepared and their antibacterial activities compared to those of erythromycin A and 9-dihydroerythromycin A. Many of the cyclic acetal derivatives showed better antibacterial activity than their parent 4. In particular, the acetaldehyde acetal (9-O,11-O-ethylidene-9-dihydroerythromycin A) (8b) showed good antibacterial activity in comparison with erythromycin A but was not sufficiently improved in vivo to warrant progression. PMID- 2925521 TI - Urdamycins, new angucycline antibiotics from Streptomyces fradiae. V. Derivatives of urdamycin A. AB - Derivatives of the angucycline urdamycin A (1) were prepared in order to study structure-activity relationships in this group of antitumor antibiotics. Derivatives of 1 formed by methanolysis, O-acylation, hydrogenation and treatment with diazomethane were isolated and characterized by their spectroscopic data. Urdamycin G (20) was isolated from Streptomyces fradiae by shortening the fermentation time. The different glycosidation pattern of the aglycone 14 did not lead to significant differences in the biological activity. O-Acylation was shown to enhance the in vitro activity of 1 against stem cells of murine L1210 leukemia depending on the lipophilicity of the molecules. The importance of the 5,6-double bond of 1 with regard to the antitumor activities is discussed. PMID- 2925522 TI - Effects of deoxyspergualin on hematopoiesis: studies of murine hematopoietic progenitor cell and peripheral blood cell levels. AB - The effect of a novel immunosuppressive agent, deoxyspergualin (DSG), on hematopoiesis in mice was studied with measurements of peripheral blood counts and assays of granulocyte-monocyte colony-forming cells (cfu-C) and spleen colony forming cells (cfu-S) in bone marrow, during and after successive intraperitoneal administration of DSG. When DSG was administered at a strong immunosuppressive dose of 6.25 mg/kg daily for 15 days, mice developed significantly decreased peripheral blood counts and decreased bone marrow cells (BMC) during administration. After the completion of DSG administration a marked rebound in leukocytosis was observed and BMC returned to normal. In contrast, total cfu-C in the femur significantly increased during the DSG administration, and subsequently returned to normal. Moreover, total cfu-S in the femur were normally sustained in contrast with a decrease of BMC during the DSG administration. These findings suggest that DSG does not show generalized overt cytotoxicity against hematopoietic stem cells and freezes the ability of the stem cell in the proliferation or the differentiation. PMID- 2925523 TI - BMY-28438 (3,7-dihydroxytropolone), a new antitumor antibiotic active against B16 melanoma. II. Taxonomy of producing organism. PMID- 2925524 TI - Direct liquid introduction LC-MS of polyene macrolide antibiotics: comment on the structure of filipin II. PMID- 2925525 TI - Efficient transformation of Micromonospora purpurea with pIJ702 plasmid. PMID- 2925526 TI - Nitracidomycins A and B, new enteromycin-group antibiotics. PMID- 2925527 TI - DC 107, a novel antitumor antibiotic produced by a Streptomyces sp. PMID- 2925528 TI - Revision of the structures of the benzo[a]naphthacene quinone metabolites G-2N and G-2A from bacteria of the genus Frankia. PMID- 2925529 TI - Following doctors' orders. PMID- 2925530 TI - Traditional Mende Society in Sierra Leone: a sociocultural basis for a quantitative research study. AB - Traditional Birth Attendants (TBAs) deliver more than 85% of the infants born in rural Sierra Leone. These midwives, who learn their skills from practice or a predecessor, are powerful women in the pervasive, secret Sande Society. Formal training programs have been established to strengthen the maternal and infant practices of these TBAs. Designing and implementing a quantitative research study to examine the effectiveness of two methods of TBA training required a strong sociocultural basis. The study was undertaken in a predominantly Mende ethnic area of Sierra Leone. I describe the significant ways in which the values and traditions of the Mende influenced the choice of research methods. Finally, I present critical questions researchers should ask to design a study that fits with the sociocultural fabric of their target population. PMID- 2925531 TI - Major health problems of women in a Kenyan village. AB - Major health problems encountered by women in one village situated in the northwestern area outside of Nairobi, Kenya, are addressed in this paper. A retrospective, descriptive account of the nature and cost of health services provided to clients is provided, with a particular focus on the three most critical health problems facing women in that village (which is a prototype of surrounding villages). Female circumcision, childbearing, and malaria are examined, and implications for change are suggested. PMID- 2925532 TI - Contribution to the validation of the SCL-90-R in French-speaking women. AB - This study is a contribution to the French validation of the Derogatis (1977) Symptom Check-List SCL-90-R. Norms reflecting the mental health status of a representative sample of French-speaking women from Montreal, Canada, are provided. Results indicated that the women in our sample generally obtained higher raw scores than those reported by Derogatis for the nonpatient group for the nine symptom scales and the three global scores. The reliability of the French version yielded a satisfactory Cronbach alpha of .91. High and significant positive correlations were found on the test-retest as well as on the Spearman Brown split-half test. Validity was assessed using the principal component analysis on six factors accounting for 88% of the variance. The correlations between the symptom scales ranged from .32 to .74, indicating the relative independence of the dimensions of the French version of the SCL-90-R. The usefulness of the method will be enhanced by further cross-validation and concurrent validity studies including patient populations. PMID- 2925533 TI - Body weight: relationship to conversational distance and self-actualization. AB - Body weight is a major concern for women. This study investigated the relationship between body weight deviation, perceived effect of weight, conversational distance, and self-actualization in healthy caucasian college women (N = 109) between the ages of 18 and 50. The perception of body weight was measured with a structured questionnaire. Conversational distance was measured by having the participant approach the investigator, and self-actualization was determined using the Personal Orientation Inventory (POI). Significant correlations were found between the Time Competence (TC) subscale of the POI and Perceived Effect (PE) and between conversational distance and TC. Further analysis of the data revealed a relationship between body weight deviation, using the actual deviation from the norm, and the combined effect (magnitude and direction) of body weight (r = .54, p less than .001). Path analysis revealed the multidimensional nature of the issue of body weight for women. The usual assumptions about body fat for women are questioned and implications for future research are discussed. PMID- 2925534 TI - Use of social support in a transition house for abused women. AB - It is recognized that individuals with healthy support systems withstand stress and crisis better than those without such support. The way in which support is used has not been specified. Using data gathered during interviews with eight women who had recently spent time in a transition house, a framework for a process of use of social support is discussed. This framework was developed using a phenomenological approach. In the framework can be found four stages that an individual passes through in using social support. Each stage is defined by a need to be met and an action the individual takes in attempting to meet that need. The specific implications for those working with clients in each of the four stages are discussed and difficulties that might occur in working with a group of clients, each at a different point in the process, are identified. PMID- 2925535 TI - Women, subjective depression, and water exercise. AB - Nearly one fourth (N = 21) of the women participants of a water exercise program (N = 88) reported feeling depressed at the time of enrollment. All the depressed women reported improvement after 8 weeks or more in the program. The subjectively depressed participants differed significantly from other class members in physical problems, lifestyle habits, and emotional concerns they hoped to address and in motivation, perceived helpful conversation with peers, and learning from the classes. Subjective symptoms are discussed in light of current information on depressive disorders. The findings contributed to the growing body of research linking exercise with the treatment and prevention of depression. Recommendations for the conduct of similar exercise programs that will be responsive to the needs of subjectively depressed women are offered. PMID- 2925536 TI - Responses of Beijing black hogs to porcine somatotropin. AB - Somatotropin treatment of U.S-breed finishing hogs improves feed efficiency, growth rate and carcass lean-to-fat ratio. Because Chinese-bred hogs have poorer feed efficiency, growth rate and lean-to-fat ratio than U.S. bred hogs, the characteristics affected by porcine somatotropin (PST) may respond differently to treatment. In the present experiment, Beijing Black finishing hogs (a composite of a local Chinese, Berkshire and Yorkshire breeds) were treated with PST for 28 d from average initial to final weights of 67.8 to 96.6 kg. In hogs individually fed as much as they would eat four times a day (n = 12/treatment group, six gilts and six barrows), feed efficiency was improved by 22.4 and 29.9% by 2 and 4 mg/d PST, respectively (P less than .01), primarily due to increased growth rate (22.1 and 32.6% greater than control, respectively, P less than .01); feed intake was not affected. Performance of group-housed and group-fed hogs (six/pen, four pens/treatment) administered 2 mg/d PST for 28 d (average initial and final weights of 66.5 +/- 1.7 and 94.0 +/- 2.4 kg, respectively) was similar (22.7% improved feed efficiency, P less than .01; 25% increased growth rate, P less than .01). At slaughter, last rib backfat thickness was decreased an average of 19.2% for hogs treated with 2 and 4 mg/d PST (P less than .01). Percentage of total muscle, obtained by physical separation of the half-carcass, was increased an average of 13.5% (P less than .01), whereas percentage of total fat was decreased 21.8% (P less than .01) in PST-treated hogs. The pH, water-holding capacity and meat color scores of longissimus muscle from PST-treated hogs did not differ from those of control hogs. Growth rate, feed efficiency and muscle weight responses to PST treatment were at least as large as those for U.S. breeds. PMID- 2925537 TI - Influence of diet on basal and growth hormone-stimulated plasma concentrations of IGF-I in beef cattle. AB - The effects of nutrition on plasma concentrations of insulin-like growth factor-I (IGF-I) were characterized in steers under basal conditions and following single i.m. injection of bovine growth hormone (bGH, .1 mg/kg BW). Nutritional effects on IGF-I were studied in three trials. In all trials steers were individually fed and penned Angus or Hereford x Angus (280 kg). In the first trial, two diets (LPLE1: 8% CP and 1.96 Mcal ME/kg, 4.5 kg.hd-1.d-1; MPHE1: 11% CP, 2.67 Mcal ME/kg, 6.5 kg.hd-1.d-1) were fed (n = 5/diet). Plasma IGF-I concentrations averaged 74 (LPLE1) and 152 (MPHE1) ng/ml (P less than .02). Following bGH injection, IGF-I increased to peak concentrations between 12 and 24 h (averaging 105 and 208 ng/ml at peak for LPLE and MPLE, respectively, P less than .01). In the second trial, steers were fed diets composed of 8, 11 or 14% CP and 1.96 or 2.67 Mcal ME/kg dry matter (6.35 kg.hd-1.d-1 in a factorial arrangement for 84 d, n = 4/diet). Within the low ME diet groups, plasma IGF-I was similar in steers fed 11 and 14% CP but greater at these two CP levels than in steers fed 8% CP (P less than .05). Within the high ME diet groups, plasma IGF-I increased linearly with CP (P less than .01). In the third trial, steers were fed diets to result in a negative N status. Insulin-like growth factor-I was lower (P less than .02) during feed restriction than when steers were full-fed. The IGF-I response to bGH was diminished or absent in underfed steers (P less than .01). These data are interpreted to suggest that diet composition and intake affect plasma concentrations of IGF-I in steers. In cattle, CP may be the primary nutritional determinant of basal IGF-I, but the IGF-I response to CP may be affected by the available ME. Undernutrition can attenuate the IGF-I response to GH and uncouple the regulation of IGF-I normally ascribed to GH. PMID- 2925538 TI - Bilateral removal of the cauda epididymides in the neonatal pig as a technique for creating teaser boars. AB - Five pairs of crossbred littermate boars were used to assess the efficacy of bilateral removal of the cauda epididymides at an early age as a technique for creating teaser boars. The cauda epididymides were surgically removed in one of each litter pair; the other of the pair served as an intact control. Boars subjected to removal of the epididymides (Epid) were rendered sterile by the technique. The Epid-treated and control untreated littermate boars had similar levels of sexual aggression and libido, as measured by behavioral characteristics at semen collection. The Epid-treated boars showed a slight, but not significant, reduction in ejaculate volume. Upon slaughter at 273 d of age, Epid and control boars had similar weights for the accessory sexual organs and penis and similar penile lengths. The Epid-treated boars displayed enlarged caput epididymides and granulomata. It is suggested that bilateral removal of the cauda epididymides in the neonatal pig may prove a worthwhile alternative to the traditional vasectomy procedure to create teaser boars. PMID- 2925539 TI - Effect of exogenous thyroxine on the interval from weaning to estrus of the primiparous sow. AB - A total of 159 primiparous sows were fed 0 (C) or 675 mg/d of thyroprotein (TP) from d -2 until d 14 postweaning. Sows received 8 (LE) or 14 (HE) Mcal of ME/d during a 28-d lactation period. Plasma levels of 3,5,3'-triiodothyronine (T3) and 3,5,3',5'-tetraidothyronine (T4) were determined for d -4, -2, 0, 1, 2, 3, 5 and 7 postweaning. Sows consuming LE lost more weight and backfat during lactation (P less than .01) than HE sows. Litters of sows consuming LE gained less weight than litters of sows consuming HE (P less than .01). Thyroprotein increased plasma levels of both T3 and T4 (P less than .01), whereas energy intake had no effect (P greater than .10) on either of the two hormones. The response to thyroid hormone was not consistent across days postweaning (TP x day, P less than .01). Feeding TP increased T4 (P less than .01) on all days, and T3 was increased (P less than .05) on d 0, 2 and 3 postweaning. Thyroid hormones rose markedly following weaning regardless of TP level. Percentage of sows in estrus by d 7 postweaning for LE-C, LE-TP, HE-C and HE-TP were 80, 78, 92 and 90, respectively. Energy restriction during lactation resulted in fewer sows returning to estrus by d 7 (P less than .03) than those fed HE. However, feeding TP postweaning had no effect on return to estrus, suggesting that the effect of dietary energy restriction during lactation on the interval from weaning to first estrus is not mediated through postweaning thyroid hormone concentrations. PMID- 2925540 TI - Interrelationships between sex and exogenous growth hormone administration on performance, body composition and protein and fat accretion of growing pigs. AB - Forty-five pigs with an average initial live weight of 60 kg were used to investigate the effects of daily exogenous porcine pituitary growth hormone administration at two dose levels (pGH; 0, excipient buffer injected, and 100 micrograms.kg-1.d-1) for a 31-d period on the performance and body composition of boars, gilts and barrows allowed to consume feed ad libitum. Excipient boars consumed less feed, exhibited faster and more efficient growth (P less than .01) and produced less fat and more protein and water (P less than .01) in the empty body compared with excipient barrows, which in turn contained more fat and less water (P less than .05) in the empty body than did excipient gilts. These differences were largely eliminated by pGH administration, which induced differential effects in growth performance and body composition in boars, gilts and barrows. Growth hormone administration improved growth rate by 13, 22 and 16% and feed conversion efficiency by 19, 34 and 32% in boars, gilts and barrows, respectively. The reduction of body fat content (g/kg) elicited by pGH was 22, 36 and 33% for boars, gilts and barrows, respectively, with a corresponding increase (P less than .01) of body protein and water content. The magnitude of the pGH responses was greatest for gilts and barrows compared with boars, negating intrinsic sex-effect differences in growth performance and body composition of pigs. Pigs used in this study and treated with pGH exhibited a rate of protein deposition (approximately 225 g/d) far greater than previously reported, and as such redefine the genetic capacity for lean tissue growth by the pig. PMID- 2925541 TI - Rapid [14C]heptachlor clearance from body stores of ovines: ingested mineral oil and parenteral trans-stilbene oxide lack effects. AB - Recently we reported elimination of radioactivity from [14C]heptachlor from body stores of lactating ovines, mainly into excreta rather than milk, contrasting sharply with bovines. To further assess heptachlor metabolism and clearance by ovines, 12 fine-wool wether lambs (41 +/- 3 kg) housed in metabolism stalls were fed pelleted alfalfa hay (96%) plus molasses (3%) ad libitum and were dosed i.p. once with [14C]heptachlor (1.643 mg/kg body wt; sp. act. = .89 microCi/mg). Feces and urine were collected separately and quantitatively. Light mineral oil was mixed with feed (5 g/100 g) of six lambs and trans-stilbene oxide, an inducer of biotransformational enzymes, was administered i.p. (4 g/hd initially; 2 g/hd daily thereafter) through 20 d to three lambs given each mineral oil treatment, in 2 x 2 factorial arrangement. Feces, urine, blood, bile and body tissues were assayed for total 14C activity. Radioactivity (heptachlor and [or] metabolites) eliminated into excreta during 21 d amounted to 34 to 36% of dose administered, of which 67% appeared in urine and 33% in feces. Biological half-time for elimination into excreta was 11.3 d [Kel = -.061/d], similar to 11.7 d we reported for lactating ewes. Clearance from blood had T1/2 = 14 d. Neither mineral oil nor trans-stilbene oxide altered rate or route of 14C activity excreted or concentrations of 14C activity in blood. Results confirmed that ovines eliminate heptachlor much more rapidly than bovines. PMID- 2925542 TI - Reproductive and growth responses of gilts to exogenous porcine pituitary growth hormone. AB - Forty gilts (mean wt = 72 kg) were administered daily either vehicle (C = control) or 70 micrograms porcine growth hormone (pGH)/kg BW. After 30 d of treatment, eight gilts per group (Exp. 1) were slaughtered and blood, uteri and ovaries were collected. Follicular fluid (FFl) was collected and granulosa cells (GC) were cultured. The remaining gilts (Exp. 2) were treated for up to 35 additional days and examined twice daily for estrus. Estrusal gilts were removed from the experiment. Noncyclic gilts (n = 9 of 12 pGH; n = 4 of 12 C) were slaughtered on d 66 and their ovaries were examined. Ovarian weights were not different for pGH and C gilts in either Exp. 1 (P greater than .1) or Exp. 2 (P = .09). Uterine weights were greater for pGH-treated than for C gilts (P less than .007) in Exp. 1, but not in Exp. 2. Concentrations of estradiol (E2) in plasma and FF1 and of progesterone (P) in plasma and FF1 were not different for pGH and C gilts. Concentrations of insulin-like growth factor-I (IGF-I) in FF1 and in serum were greater for pGH than for C gilts (P less than .01). Concentration of P in serum-free medium of cultured GC was lower for GH than for C (P less than .05) in the presence or absence of gonadotropins in Exp. 1. The FSH-stimulated secretion of P was also lower for GC of pGH-treated gilts in Exp. 2, indicating a failure of GC to differentiate in culture. Only one pGH gilts in Exp. 2 manifested estrus, compared with seven C gilts (P less than .025). In Exp. 1, ADG was higher (P less than .03) and feed/gain lower (P less than .07) for pGH gilts. Longissimus muscle area (LMA) was not different (P = .19) between groups. Backfat thickness (BF) was lower (P less than .005) in pGH than in C in both Exp. 1 and 2. We conclude that exogenous pGH increased growth rate, improved feed efficiency and altered carcass traits in gilts. However, these effects were associated with impaired ovarian development of prepubertal gilts and a low incidence of estrus. PMID- 2925543 TI - Androgen and estrogen receptors in bovine skeletal muscle: relation to steroid induced allometric muscle growth. AB - The presence of free androgen (AR) and estrogen receptors (ER) was demonstrated in bovine skeletal muscle. Androgen receptor concentrations in neck muscle from cattle of different sexes and stages of development were related to hormonal status. In mature bulls (mean weight 600 kg), no free AR was detectable. Highest AR concentrations were measured in mature bulls (517 kg) castrated 24 h prior to slaughter (.85 +/- .21 fmol/mg protein). In female calves (155 kg), AR concentrations (.56 +/- .14 fmol/mg) were greater (P less than .01) than in male calves (.20 +/- .08 fmol/mg) of the same weight. Androgen receptors and ER in skeletal muscle of neck, shoulder, abdomen and hind leg of female and male calves were compared. There was no significant difference between AR concentrations in the neck, shoulder and hind leg, but concentrations were lower (P less than .05) in abdominal muscle. Estrogen receptor concentrations in neck, shoulder, abdomen and hind leg were not different between sexes (P less than .05). In male calves, ER content was lower (P less than .05) in abdominal than in other muscles. Estrogen receptor concentrations in muscles of female calves did not differ (P less than .05). The pronounced sensitivity to estrogens and androgens in the neck, shoulder, and hind leg of calves, being free of the respective hormone, may partly explain the characteristic conformation in calves treated with estrogenic and androgenic steroids and the sexual dimorphism of muscle growth. PMID- 2925544 TI - Sampling intensities and replication requirements for detection of treatment effects on testicular function in bulls and stallions: a statistical assessment. AB - Data from testes of 16, 2- to 3-yr-old stallions and 34 yearling beef bulls were utilized in a components of variance approach to calculate the number of observations required per testis and(or) the number of animals required per treatment group to provide experiments of known sensitivity and precision, where treatment was to be assessed by one of several endpoints. The latter included paired testes weight, seminiferous tubular diameter, the number of germ cells per seminiferous tubular cross-section, or the number of elongated spermatids per gram of testicular parenchyma or per testis. For all variables for which several observations were available for each testis, precise assessment of any given male required far fewer observations than have been used routinely. However, replication requirements varied substantially in relation to the sensitivity (i.e., size of difference to be detected) and precision (i.e., Type I and II error probabilities) desired. Replication requirements were greater for stallions than for bulls, particularly at higher levels of sensitivity, for which requirements for both species were very large. The data presented should permit future experiments involving assessment of these endpoints to be designed with known sensitivity and precision and with optimal efficiency and cost effectiveness. PMID- 2925545 TI - Effects of supplemental silage on forage intake and utilization by steers grazing wheat pasture or bermudagrass. AB - Seven trials were conducted to determine the effects of increasing amounts of silage (corn, wheat or sorghum) on forage intake, gastrointestinal tract fill, fecal output and ruminal flow and degradation of forage by cattle grazing wheat pasture or bermudagrass. In each of 3 yr, 24 steers grazed a common wheat or bermudagrass pasture and were randomly allocated to four treatments (0, .35, .70 or 1.05 kg silage DM.100 kg body weight-1.d-1). Intake and ruminal flow of forage were measured by feeding a single pulse dose of Yb-labeled forage followed by collection of fecal samples for 4 to 5 d and fitting Yb concentrations to a one compartment, age-dependent model. Ruminal digestion kinetics of wheat forage were estimated in situ using eight ruminally cannulated steers fed 0 or .55 kg sorghum silage DM.100 kg body weight-1.d-1. Supplemental silage decreased wheat forage (P less than .10) and bermudagrass (P less than .01) intake linearly. However, total forage intake of bermudagrass plus silage increased linearly (P less than .05). Each kilogram of added silage DM decreased DM intake of wheat forage by .66 +/- .25 and of bermudagrass by .63 +/- .17 kg. Flow and turnover of wheat forage or bermudagrass were not altered (P greater than .15) by supplemental silage. Silage consumption increased extent of ruminal degradation of wheat forage DM (P less than .05; 63.1 vs 52.5%), indicating a positive associative effect of silage on wheat forage utilization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2925546 TI - Cupric oxide needles for grazing cattle consuming low-copper, high-molybdenum forage and high-sulfate water. AB - Oxidized copper wire, commonly referred to as copper oxide needles (CuON), was evaluated using purebred Hereford cows and their calves. Thirty-seven cows were allocated to Cu treatments of 0, 25 or 50 g CuON (79.9% Cu in CuON) with 12, 12 and 13 cows per treatment, respectively; calves within cow treatments were allocated to treatment of 0 and 20 g CuON. Single oral doses of CuON were given at the start of a grazing trial that lasted 92 d. Cows and calves were weighed and blood samples were taken on d 0, 28, 63 and 92; liver biopsies were taken on d 0, 28 and 92 of the grazing trial. Cattle were consuming grass forage with mean concentrations on d 0, 28, 63 and 92 of the grazing trial ranging from 1.6 to 5.5 mg/kg DM for Cu, 2.5 to 5.5 mg/kg DM for Mo and 1.3 to 1.5 g/kg DM for total S. The water consumed by cattle contained 947 mg sulfate per liter (SE = 13.2, n = 4). Body weight of cows and calves was not influenced (P greater than .05) by CuON. Liver Cu was higher (P less than .01) in treated cows and calves but was not different (P greater than .05) between cows dosed with 25 or 50 g CuON. Treatment of cows and calves with CuON had no influence (P greater than .05) on the concentration of Fe or Mo in liver or plasma, the concentration of Cu and ceruloplasmin activity in plasma, or the concentration of Zn in liver. Plasma Zn did not differ (P greater than .05) in cows, but it was higher (P less than .05) in the calves suckling cows treated with CuON. It was concluded that dosing cows and calves with CuON resulted in a higher Cu content of liver but did not adversely influence the metabolism of Fe or Zn or modify the concentration of Mo in the plasma or liver of cows or calves. PMID- 2925547 TI - Evaluation of soybean meal, corn gluten meal, blood meal and fish meal as sources of nitrogen and amino acids disappearing from the small intestine of steers. AB - The value of soybean meal (SBM), corn gluten meal (CGM), blood meal (BM) and fish meal (FM) in supplying N and amino acids (AA) escaping ruminal microbial degradation and disappearing from the small intestine (SI) was studied in steers using a regression approach. Replacement of corn starch in diets with protein sources resulted in decreases (P less than .05) in efficiency of microbial protein synthesis. Ruminal ammonia-N (NH3-N) had the greatest increase (P less than .05) when SBM was fed; BM supplementation resulted in only nonsignificant increases in ruminal NH3-N (P greater than .05). Soybean meal had the lowest proportion of N escaping ruminal degradation (.21). Corn gluten meal-N (.86) and BM-N (.92) escaped ruminal degradation to the greatest extent, and FM-N was intermediate (.68). Protein sources followed similar trends in providing absorbable nonbacterial N to the SI. Thirteen (+/- 6.2) percent of SBM-N was absorbed from the SI; 69 (+/- 6.2), 68 (+/- 9.1) and 50 (+/- 10.1)% of CGM-N, BM N and FM-N, respectively, were absorbed from the SI. Values for ruminal escape and SI availability for individual and total AA are presented. Of the essential AA (EAA), threonine, valine and isoleucine were more resistant to ruminal degradation; methionine, cysteine, histidine and arginine were more extensively degraded than the total AA supply. Of the EAA escaping ruminal degradation, cysteine, histidine and threonine tended to be less digestible, whereas arginine was more digestible in the SI than the total AA supply. PMID- 2925548 TI - Uterine secretory alterations coincident with embryonic mortality in the gilt after exogenous estrogen administration. AB - Sixteen crossbred gilts were assigned randomly to receive either an i.m. injection of sesame oil (control) or estrogen (E), 5 mg of estradiol valerate, on d 9 and 10 of pregnancy. Gilts were unilaterally hysterectomized on either d 12 and 14 or 16 and 18. Uterine horns were flushed with 20 ml of .9% sterile NaCl solution to recover conceptus tissue. Conceptuses and endometrial explants were cultured for 24 h with 100 microCi [3H] leucine in 15 ml of minimum essential media. After dialysis, culture media were submitted to 2D-polyacrylamide gel electrophoresis and incorporated proteins were analyzed by fluorography. Normal, intact conceptus tissue was recovered from control gilts. Estrogen-treated gilts flushed on d 12 and 14 contained intact conceptuses; however, uteri from two gilts on d 16 and three on d 18 contained degenerating conceptus tissue. Comparison of endometrial polypeptides synthesized in vitro indicated an alteration in E-treated gilts on d 12 through 18. Although similar polypeptides were present, a band of polypeptides with a Mr of approximately 30,000 and pI from 7.9 to 8.9 and a larger, acidic polypeptide (Mr = 100,000, pI 3.5 to 5.0) were faint or absent in E-treated gilts. Conceptuses elongated normally in the altered uterine environment, but failed to survive past d 14 in E-treated gilts. Although loss of specific polypeptides in E-treated gilts coincides with conceptus death, their function in conceptus development or attachment is unknown. PMID- 2925549 TI - Structural and metabolic integrity of sheep external intercostal muscle during extended culture. AB - The objectives of this study were to examine the structural and metabolic integrity of isolated sheep external intercostal muscle bundles following variable lengths of preincubation (0 to 192 h). Samples of intact external intercostal muscle (10 to 15 g), with tendons attached, were prepared from growing wethers and maintained at their resting lengths during preincubation for 0 to 192 h. Protein synthesis (PS), protein degradation (PD), acetate oxidation and ultrastructural integrity of muscle samples were examined at 0 to 192 h, 0 to 96 h, 0 to 48 h and 0 to 96 h following isolation, respectively. Additionally, the effects of variable fetal calf serum (FCS) concentrations (0 to 20%; w/v) on PS and PD and acetate oxidation were examined. Rate of PS increased as preincubation time increased to 192 h; however, most of this increase was due to the proliferation of fibroblasts on the surface of the muscle sample. Addition of cytosine arabinoside to the incubation media prevented the fibroblast-dependent increase in PS; however, it did not entirely prevent the preincubation time dependent increase in PS. Rate of PD increased greatly upon preincubation. The nitrogen balance of incubated muscles was negative at all times examined. Acetate oxidation was maintained through 12 h of preincubation and thereafter declined. Relatively normal myofibrillar structure was maintained through 48 h of preincubation; however, loss of mitochondrial integrity and dissolution of Z disks at 48 h and at 96 h of preincubation were evident. Isolated tissues were able to respond to FCS concentration in medium following 48 h of preincubation. PMID- 2925550 TI - Effects of additional feed during late gestation on reproductive performance of sows: a cooperative study. AB - A cooperative research study involving 1,080 litters was conducted at eight stations to determine the effects of additional feed during the last 23 d of gestation on reproductive performance of sows and on preweaning performance of their pigs. Primiparous and multiparous sows were fed fortified corn- or sorghum soybean meal diets (14% crude protein). Control sows received 1.82 kg/d from March through November and 2.27 kg/d from December through February. Treated sows were fed an additional 1.36 kg of feed/d from d 90 of gestation to farrowing. Sows were allowed to consume the same diet ad libitum during a 21-d lactation. Additional feed in late gestation resulted in greater (P less than .001) sow weight gain from d 90 to d 110 of gestation (16.8 vs 9.0 kg) and greater (P less than .001) parturition-lactation weight loss (21.3 vs 16.4 kg). Total weight gain from breeding to 21 d of lactation favored sows that received extra feed (27.5 vs 22.7 kg; P less than .001). Sows receiving extra feed had more live pigs at farrowing (10.05 vs 9.71, P = .06) and at 21 d postpartum (8.35 vs 8.06, P = .09), and the pigs were heavier at birth (1.48 vs 1.44 kg, P = .003) and at 21 d (5.37 vs 5.20 kg, P = .006). Lactation feed intake and number of days from weaning to estrus were not affected by treatment. The results indicate that additional feed in late gestation improves reproductive performance in sows. In this study, the cost of an additional 31 kg of feed/sow was more than offset by the value of the additional sow weight gain (approximately 5 kg), the additional .3 of a pig/litter at weaning and the additional 2.6 kg of total litter weaning weight. PMID- 2925551 TI - Evaluation of crossbreeding systems for small beef herds: II. Two-sire systems. AB - Stochastic computer models were used to evaluate nine crossbreeding systems in beef herds consisting of two bulls, 50 cows and 15 replacements. Systems examined were: 1) purebred (PB), 2) two- and three-breed rotations using natural service (2R and 3R) or artificial insemination (2RAI and 3RAI), 3) two-breed roto terminals not exploiting complementarity using natural service (2RT) or AI (2RTAI) and 4) two-breed roto-terminals exploiting complementarity using natural service (2RTC) or AI (2RTCAI). Average heterosis estimates were taken from literature sources. Replacement females were produced within the herd; sires were purchased. Estimates of calf and dam heterosis were used to calculate performance of calf weight weaned and sold, cow and total weights sold and gross calf, cow and total incomes. All crossbred systems were superior to PB for weights sold and income. The natural-service systems (2R, 3R, 2RT and 2RTC) utilized 90 to 98% of the heterosis available in their AI counterparts (2RAI, 3RAI, 2RTAI and 2RTCAI). No differences were found between corresponding natural-service and AI systems for weights sold and incomes. Increasing the complexity of the system did not provide important improvements in traits measured. PMID- 2925552 TI - Effects of diet and climate on growing horses. AB - The effects of diet and climate were assessed in 42 light horse weanlings over 30 wk. Horses were fed diets varying in energy and phosphorus content. Diets were predominantly forage (73 to 77.5%) or concentrate (62 to 62.25%) and had 2.65 or 3.09 Mcal DE/kg DM, respectively. Horses were weighed every 14 d. Group feed intakes and climatic variables were recorded daily. Dietary phosphorus content did not affect intake or gain. Horses fed forage diets ate 18% more (P less than .001) DM than horses fed concentrate, but DE intakes did not differ. Average DE intakes, 21.5 Mcal daily, were 33% more than those given in 1978 National Research Council (NRC) tables. Overall ADG by forage- and concentrate-fed horses were .83 and .89 kg, respectively. These values were 23 and 32% above mean ADG values given for horses at 6 and 12 mo in 1978 NRC tables. Average daily gain declined (P less than .01) with age, although daily DE intake increased (P less than .01). Total DM and DE intakes were determined largely by body weight, but age was the main determinant of weight-scaled DE intake. Weight- and age-scaled DE intakes were reduced (P less than .001) by 6.1% at temperatures below -10 degrees C compared with temperatures above -10 degrees C. Temperatures below -20 degrees C had no greater effect on DE intake than those between -10 to -20 degrees C. Neither precipitation nor wind alone affected weight- and age-adjusted DE intake. In conclusion, weanling horses fed readily digested diets ad libitum gained weight at or above expected values even at severely cold ambient temperatures. PMID- 2925553 TI - Serving capacity of crossbred yearling beef bulls. I. Single-sire mating behavior and fertility during average and heavy mating loads at pasture. AB - Eighty crossbred, virgin, yearling beef bulls were subjected to three serving capacity (SC) tests. Ten low SC (LSC) and 10 high SC (HSC) bulls similar in weight (avg wt = 452 kg), testicular size and seminal traits but differing in average services were selected. Objectives were to evaluate the mating behavior and fertility of LSC and HSC bulls at pasture when exposed to an average and a heavy mating load and to determine the effect of sexual activity on body weight and testicular characteristics. One LSC and one HSC bull per block were exposed single-sire to 25 naturally cyclic (N) cows for 3 d and to 9 estrus-synchronized (S) cows for 1 d in a randomized complete block design consisting of 10, 4-d blocks. Bulls were fitted with pedometers to record distance travelled. Behavioral data were collected by periodic visual observation. During the N cow treatment, LSC bulls had fewer (P less than .05) services per cow, total services and a higher mount to service ratio than HSC bulls. During the S cow treatment, LSC bulls showed increased sexual activity, though they achieved fewer (P less than .09) services per cow. Pregnancy rates for LSC and HSC bulls did not differ (P greater than .20) and across SC groups averaged 53.6% for N cows and 31.9% for S cows. Distance travelled also was similar (P greater than .20) between SC groups for both treatments. Sexual activity during pasture exposure had no effect (P greater than .20) on testicular characteristics but resulted in an average decline in body weight of 25.7 kg across SC groups during the 4-d period. Post exposure SC tests found that LSC bulls had increased (P less than .05) services, decreased mounts and mount to service ratio compared to pre-exposure measurements, but LSC were still lower (P = .06) than HSC bulls for average services. These results suggest that LSC virgin, yearling bulls should be offered sexual experience and retested before their inherent SC can be determined. PMID- 2925554 TI - Serving capacity of crossbred yearling beef bulls. II. Summer grazing activity and body temperature patterns during average and heavy mating loads at pasture. AB - Ten low (LSC) and 10 high (HSC) serving capacity yearling bulls were exposed individually to 25 naturally cyclic (N) cows for 3 d (average mating load) and subsequently to 9 estrus-synchronized (S) cows for 1 d (heavy mating load) in a randomized complete block design consisting of 10, 4-d blocks. Bulls were fitted with vibracorders and temperature acquisition modules to record grazing activity and body temperature (BT), respectively. During the N cow treatment, LSC bulls had fewer (P less than .05) services per cow and a higher mount to service ratio than HSC bulls, and LSC bulls tended (P = .12) to graze less total time than HSC bulls (7.8 vs 9.0 h/d, respectively). However, both groups of bulls exhibited similar diurnal grazing patterns with two major daily grazing periods; the first (0400 to 1300) peaked early in the morning (0600) and the second (1700 to 2200) occurred in late afternoon and evening. During the S cow treatment, LSC and HSC bulls did not differ (P = .60) in grazing time or pattern, but similar mating activity was exhibited by both SC groups while exposed to S cows. Bulls grazed little during the hottest part of the day (1300 to 1700), and LSC and HSC bulls spent only 2.2 and 2.4 h, respectively, grazing during dark, cooler periods near midnight. Body temperature did not differ between SC groups and averaged 39.3 degrees C during N cow treatment and 39.4 degrees C during S cow treatment. Body temperature had a distinct, monophasic diurnal pattern in bulls exposed to an average mating load.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2925555 TI - Effects of sow-crate design on health and performance of sows and piglets. AB - The effects of sow-crate design on certain health and performance traits of 211 sows and their piglets were evaluated with a 2 X 2 X 4 factorial arrangement of crate width (narrow [N = 55 cm] or wide [W = 64] between lowest horizontal pipes), length (short [S = 183 cm] or long [L = 198] from rump stop to front gate) and side type (lower side of sow crate "fingered" [F], "bowed" bottom bar- marking the sow zone 19.3 cm wider at the bottom--20 cm above the floor [B], or straight bottom bar 20 cm [S20] or 25 cm above the floor [S25]). Between d 107 to 110 postcoitum and d 21 postpartum, no crate design variable affected the sow's body-weight change, but side type tended to affect the most prominent head-neck and leg integumentary lesions. Number of stillborn piglets/litter was greater with W crates than with N, except with crates having S20 sides, and was greater with L crates than with S. More piglets were crushed to death in W crates than N crates, and stillbirth frequency was greater in L crates than in S, but overall preweaning piglet mortality was affected by no crate-design feature. At both 7 and 21 d of age, piglets' knee lesions were most severe with S20 crates and least with S25, whereas face-lesion score was unaffected by crate design. Piglet body weight at age 21 d was least with S20 crates and greatest with F and S25. No crate-design variable affected within-litter variation in piglet growth rate. Sow crate design affected important health and performance traits of piglets through postnatal d 21. PMID- 2925556 TI - Effects of sow-crate design on sow and piglet behavior. AB - The effects of sow-crate design on certain behaviors of sows and piglets at farrowing and again approximately 3 wk later were evaluated with a 2 x 2 x 4 factorial arrangement of crate width (narrow [N = 55 cm] or wide [W = 64] between lowest horizontal pipes), length (short [S = 183 cm] or long [L = 198] from rump stop to front gate) and side type (lower side of sow crate "fingered" [F], "bowed" bottom bar 20 cm above the floor [B], or straight bottom bar 20 cm [S20] or 25 cm above the floor [S25]). Farrowing-crate design influenced both sow and piglet behaviors both during and immediately after parturition and during nursing suckling bouts approximately 3 wk later. Activities of 51 sows and their piglets were videorecorded during and immediately following parturition. Sow-crate design affected neither the interval between births of successive piglets in a litter nor the frequency of standing by the sow during parturition. Latency from birth to first mammary contact (LMC) was greater with S25-sided and S sow crates, and especially with S, W crates. A significant interaction occurred between sow-crate side type and dimensions; LMC was longer when S25 sides were combined with S or W crates. Data on suckling behavior were collected from 113 litters over three successive sucklings approximately 3 wk after farrowing. Sow-crate design had no effect either on the consistency with which a piglet suckled a particular teat or teat pair or on the frequency of multiple-teat use. Piglets maintained fewer functional teats with S, S20 crates. The distribution of functional teats between rows was less symmetric with S crates. Piglets nursed with their bodies over a side bar more frequently with B- and S20-sided crates. The sow permitted her piglets to suckle while she was in a vertical stance more frequently with S and N crates, and especially with S, N crates. Sow-crate design affected important behaviors of sows and piglets both during and immediately after parturition as well as during nursing-suckling bouts about 3 wk later. PMID- 2925557 TI - Role of sex, gender roles, and attraction in predicting emergent leaders. PMID- 2925558 TI - Achievement strivings, scholastic aptitude, and academic performance: a follow-up to "impatience versus achievement strivings in the type A pattern". PMID- 2925559 TI - A causal model of the relationship among accidents, biodata, personality, and cognitive factors. PMID- 2925560 TI - Sex differences in sustained attention across the adult life span. PMID- 2925561 TI - Improved antenatal sex determination of baboon amniocytes using Chang Medium growth factor supplement. PMID- 2925562 TI - Further purification of a fibroblast growth factor-like factor from chick embryo extract by heparin-affinity chromatography. AB - A mitogenic factor which promotes quail myoblast proliferation has been purified some 10(5)-fold from chick embryo extract by a combination of cation-exchange chromatography and heparin-affinity chromatography. The factor is eluted from heparin-Sepharose with 2 M NaCl and is a single-chain polypeptide with an apparent molecular weight of 15,000 to 17,000. It is active at subnanogram level in triggering the proliferation and thereby delaying temporarily fusion of myoblasts. It also stimulates the proliferation of quail fibroblasts in a similar effective concentration range. For both myoblasts and fibroblasts the dose response to the factor is quantitatively and qualitatively comparable with that of bovine pituitary fibroblast growth factor. These observations strongly suggest that the factor very probably corresponds to chicken fibroblast growth factor or to a closely related molecule(s) and that it is possibly involved in the regulation of myogenesis. PMID- 2925563 TI - Partial purification and characterization of immunoglobulin production stimulating factor derived from Namalwa cells. AB - We screened for immunoglobulin (Ig) production stimulating factor (IPSF) which enhanced Ig production of human-to-human hybridomas in serum-free culture, and found that culture supernatant and lysate of human lymphoblastoid Namalwa cells stimulated proliferation and Ig production of human-to-human hybridoma HB4C5 cells. The IPSF in Namalwa lysate was partially purified with DEAE-Toyopearl 650M, hydroxylapatite and Superose 6HR 10/30 column chromatographies. The partially purified IPSF was a macromolecule of about 500,000 dalton containing 72,000 dalton protein as a major component. The activity was stable at pH 6 to 12, but inactivated partially by heating over 40 degrees C (60% decrease) and completely by trypsin digestion. These results suggest that the IPSF activity is due to its protein and heat-stable components. The Namalwa IPSF stimulated proliferation of human-to-human hybridomas but not that of mouse-to-mouse hybridomas. The IPSF also stimulated Ig production of human-to-human hybridomas derived from NAT-30 cells, but not that of other human-to-human or mouse-to-mouse hybridomas. NAT-30 is a human fusion partner derived from Namalwa cells. These results suggest that the Namalwa IPSF is an autocrine factor that stimulates proliferation and Ig production of hybridomas derived from NAT-30 cells. PMID- 2925565 TI - Genetic control of variation in human gingival fibroblast proliferation rate. AB - Logarithmic proliferation rate (Days 1 to 6) of gingival fibroblasts derived from 15 pairs of monozygotic (MZ) and 9 pairs of dizygotic (DZ) human twins was compared under optimal and suboptimal growth conditions. Cell proliferation rates exhibited considerable variability among strains. For Caucasian donors (13 MZ, 6 DZ pairs) DZ twins demonstrated significantly greater (P less than 0.01) within pair variance in cell proliferation rate compared to MZ twins when evaluated under optimal growth conditions. Heritability analysis indicated strong genetic control of proliferation rate of human gingival fibroblasts (HGF) under optimal growth conditions (1.0 +/- 0.67), whereas proliferation rate of HGF under suboptimal growth conditions revealed less genetic control (0.42 +/- 0.61). These findings emphasize the importance of carefully matching control and test HGF in assays dependent on cellular proliferation. PMID- 2925564 TI - Culture of human corpus cavernosum endothelium. AB - A method for culturing endothelial cells (HCC-EC) from surgical specimens of human corpus cavernosum has been developed. The approach involves selective endothelial outgrowth from explants and may be generally applicable to tissues whose endothelium is not amenable to isolation by routine mechanical or enzymatic methods. The tissue is minced into pieces which are placed onto gelatin- or fibronectin-coated tissue culture plastic, and grown in medium suitable for microvascular endothelial cell growth (Carson and Haudenschild, In Vitro 22:344 354, 1986). By Days 5 to 7 EC colonies are found. Within a day or two after the appearance of the EC colonies, a non-EC cell type appears and, if undisturbed, quickly overgrows the EC. An exploitable temporal separation between the emergence of EC and non-EC is obtained when both conditioned medium (from bovine aortic endothelium) and retinal extract are present during the outgrowth period. Explants are removed by pipetting at the first sign of the emergence of the non EC cell type. Once isolated, HCC-EC do not require conditioned medium but do require either retinal extract or acidic fibroblast growth factor for survival and growth. Approximately 60% of the first passage cultures are at least 80% EC as judged by DiI-Ac-LDL labeling. One corpus (0.3 x 0.3 x 0.5 cm) usually produces 120 cm2 of primary culture within 2 wk. These EC form contact-inhibited monolayers and stain positively for Factor VIII. They have a doubling time at 6th passage of 48 h and a plateau density of 5 to 7 x 10(4) cells/cm2. The availability of such cultures should facilitate the study of endothelium-mediated responses which play an important role in the erectile function of human penile corpus cavernosum. PMID- 2925567 TI - Factors associated with joint custody awards. AB - Court records of 358 divorce cases involving children from matched counties in two states with opposite legal presumptions concerning joint legal custody were reviewed. The impact of such presumptions upon actual custody awards was examined, as well as the correlation between demographic and other custody arrangement variables and joint legal and physical custody in both states. It was found that the existence of a presumption concerning joint legal custody affected legal but not physical custody award patterns. Significant correlations were discovered between joint custody and the presence of specific language in court orders concerning parental rights/responsibilities and financial support for children; parental education; gender of plaintiff; welfare agency involvement and defendants' requests for custody. Implications of these findings are discussed. PMID- 2925568 TI - Father absence: effects on child and maternal psychopathology. AB - The effects of fathers' absences during the previous year on 213 military children were examined, using multiple measures of children's functioning and psychiatric symptoms. Children whose fathers had been absent 1 or more months during the previous 12 months experienced significantly higher self-reported depression and anxiety, but these symptoms were not apparent to adult observers (parents and teachers). These effects were not demonstrated when maternal psychiatric symptoms and intercurrent family stressors were controlled. Thus, the effects of father absence under routine conditions in relatively healthy samples may exert no significant effects independent of intervening family stressors or maternal psychopathology. Clinic referrals of children during times of father absence may partly be due to an effect of additional stressors impacting on the mother during the absence of the father. PMID- 2925566 TI - Maintenance of testosterone production by purified adult rat Leydig cells for 3 days in vitro. AB - Using a preparation of highly purified, adult rat Leydig cells and conditions of culture which we found to optimize testosterone production during 24 h, we sought to maintain optimal testosterone production for 3 d. Leydig cells cultured on Cytodex 3 beads at 19% O2 in Dulbecco's modified Eagle's medium-Ham's nutrient mixture F12 (1:1; vol/vol) containing 0.5 mg/ml total bovine lipoproteins (less than 1.222 g/ml) with maximal luteinizing hormone (LH) stimulation failed to maintain a constant amount of testosterone for 3 d. These cells did however secrete a similar amount of total delta 4-3-ketosteroids on each of the 3 culture d, indicating that their viability was preserved. The predominance of progesterone and 170H-progesterone relative to the amount of androstenedione found on Days 2 and 3 suggested that the activity of the cytochrome P450 C17 hydroxylase-C17,20-lyase enzyme in the smooth endoplasmic reticulum was diminished when Leydig cells were maintained in our primary culture for longer than 24 h. Decreasing the oxygen tension of the cultures from 19 to 5%, and decreasing the concentration of LH used to stimulate the Leydig cells from 100 to 0.1 ng/ml, were necessary to achieve maintenance of testosterone secretion without accumulation of other delta 4-3-ketosteroids during a 3-d period. Cells cultured in this fashion were still able to respond to maximal LH stimulation during Day 3, producing as much testosterone as if cultured for 24 h on Day 1 at 19% O2 with 100 ng/ml LH stimulation. PMID- 2925569 TI - Residential instability in adolescent inpatients. AB - The case records of 225 randomly selected adolescent psychiatric inpatients were reviewed to determine prevalence of residential instability. The study also examined the demographic, family composition, life event, and behavior characteristics associated with residential instability. Approximately 30% of the sample had experienced a high rate of residential instability (i.e., from 5 to 20 domicile moves). Analyses indicated that residential instability was associated with a set of characteristics that included caregiver neglect, caregiver abuse, parental separation, multiple hospitalizations, lower IQ, indices of poor impulse control, and antisocial behavior. The possible contribution of residential instability to treatment resistance and the development of antisocial behaviors in some adolescents is discussed. PMID- 2925570 TI - Coping with parental quarrels. AB - Children's reactions to parental quarrels were investigated in a general population sample of children between 9 and 12 years old. One hundred and thirty nine families participated in the study. Approximately half the children were living in disharmonious families and half were in harmonious families. Mothers and children were interviewed with semistructured interviews to determine how children responded to specific episodes of parental quarrelling. Seventy-one percent of children reported intervening in parental quarrels. A range of other coping strategies was identified: seeking contact with a sibling, confiding in friends, offering comfort to parents after a quarrel, self-blame, seeking information about quarrels, and perceiving beneficial aspects to parental quarrelling. The hypothesis was examined that certain coping strategies would be associated with lower levels of children's behavioral and emotional problems. Only a weak relationship was found between children's intervention in parental quarrels and emotional and behavioral problems. No other coping strategies were found to predict children's disturbance. PMID- 2925572 TI - Affect and cognition in autism. AB - An array of six photographs of the same woman was used to assess the ability of 18 autistic, 14 nonautistic mentally retarded, and 18 normal preschool subjects to use affect- and activity-related concepts in the solution of cognitive tasks. The Total Performance Level of the autistic and mentally retarded subjects did not differ significantly. Autistic subjects performed imitation, directed action, and description tasks less well in the affect mode. The findings are consistent with other studies, suggesting an impairment in the expression of emotion in autism. PMID- 2925571 TI - Neurochemical study of dopamine functioning in autistic and normal subjects. AB - Plasma prolactin (PRL) and homovanillic acid (HVA) levels, and urinary HVA and dopamine (DA) excretion, were measured in groups of unmedicated autistics, medicated autistics, and normal controls. No significant differences were found between unmedicated autistics and normal controls in plasma PRL and HVA levels. Excretion rates of urinary HVA and DA were also similar in the unmedicated autistic and normal subjects. Plasma PRL and HVA, as well as urinary HVA excretion, were significantly increased in the autistics on neuroleptic medication compared to the unmedicated autistics. A significant correlation (r = 0.46, p = less than 0.05) was observed between dose of neuroleptics and plasma PRL values; the correlation (r = 0.42) between neuroleptic dose and plasma HVA levels approached significance (p = 0.06). In contrast, no differences were observed in urinary DA excretion between medicated and unmedicated autistics. In general, the findings indicate that peripheral indices of dopamine functioning are normal in autistic subjects. PMID- 2925573 TI - Naltrexone in autistic children: an acute open dose range tolerance trial. AB - The safety and efficacy of naltrexone was explored in an open acute dose range tolerance trial in 10 hospitalized autistic children, ages 3.42 to 6.50 years (mean, 5.04). Naltrexone was given in ascending doses: 0.5, 1.0, and 2.0 mg/kg/day. Behavioral side effects were observed as early as 1/2 hour after dosing. Ratings on the Children's Psychiatric Rating Scale showed that withdrawal was reduced across all three dose levels; administration of 0.5 mg/kg/day dose resulted in increased verbal production; and the 2.0 mg/kg/day dose resulted in reduction of sterotypies. Mild sedation of brief duration was the only side effect. Electrocardiogram, liver function tests, and all other laboratory studies remained unchanged throughout the study. These preliminary findings require replication in a larger sample of patients under double-blind and placebo controlled condition. PMID- 2925574 TI - Influence of verbal ability on the expression of aggression in physically abused children. AB - The relationship between verbal ability and aggressive behavior in 53 physically abused children in a residential treatment center was examined. Characteristics differentiating aggressive children from their less aggressive peers were identified. Although general verbal ability was similar in aggressive and nonaggressive abused children, reading and expressive language deficits were more prevalent in the highly aggressive children. Highly aggressive children were significantly more deficient in reading ability and more often required speech language services. Implications of these findings for treatment and future research are discussed. PMID- 2925575 TI - Cognitive and physiological responsiveness of abused children. AB - Videotaped scenes of everyday events were shown to hospitalized abused and nonabused children and to a nonhospitalized peer group. The children's heart rates were taken as they viewed the scenes and they responded to questions about the content of the scenes. The hospitalized children reacted to the scenes with a larger decrease in heart rate than did the nonhospitalized children. The abused children reported more negative outcomes to the scenes, more negative feelings, and that they had experienced the events depicted more often than did either group of nonabused children. PMID- 2925576 TI - Psychiatric status of intrafamilial child sexual abuse victims. AB - The initial psychiatric profile of a large sample of sexually abused children who presented at an outpatient child psychiatry clinic was assessed. The results identified a wide diversity in victim responses to incest. The older the victim, the closer the relationship of the offender to the child, the greater the frequency of abuse incidents, the longer the duration of the abuse, the offender having a history of alcohol abuse, and the victim being a victim of physical abuse as well as sexual abuse were all related to the presence of a DSM-III axis I clinical disorder. PMID- 2925577 TI - False allegations of sexual abuse by children and adolescents. AB - The frequency of false allegations of sexual abuse by children and adolescents is of significant legal and clinical importance. The rate of false allegations of sexual abuse is examined in a large sample of Child Protective Services (CPS) cases. The criteria used by CPS workers in judging the validity of allegations are considered, and the relationship between substantiation rates and attitudes about the trustworthiness of child reports of abuse is explored. Many professionals in the field of child sexual abuse are more skeptical of child and adolescent claims of sexual abuse than available research suggests is warranted. PMID- 2925578 TI - Children's memory and proximity to violence. AB - The study examined 133 school-age children's memory of a sniper attack at their elementary school. Researchers analyzed the role that spatial representation, memory markers, inner plans of action, and strategies of recall played in the memory process. In recalling the event, exposed children reduced their degree of life threat, while nonexposed children increased their proximity to the violence. Clinical and forensic implications are discussed. PMID- 2925579 TI - Specificity of infants' response to mothers' affective behavior. AB - Mother-infant face-to-face interaction is central to infant socioemotional development. Little has been known about the mechanisms that mediate the mother's influence. Findings are reviewed from a series of laboratory studies that suggest the major functional components of a mother's behavior are its affective quality and its contingent relationship to her baby's behavior. Quality of mother's affective expression accounted for individual differences in the behavior of thirteen 7-month-old infants living in multiproblem families. Infants' response was specific to the type of affective expression mothers displayed. Flat, withdrawn maternal affective expression was associated with infant distress. Intrusive maternal expression was associated with increased gaze aversion. Lack of contingent responsiveness was common to all but four mothers. Findings suggest that withdrawn or intrusive maternal affective expression, together with lack of contingent responsiveness, may in part be responsible for the risk-status of infants in multiproblem families. PMID- 2925580 TI - Affect attunement, attachment, temperament, and zygosity: a twin study. AB - A twin study examines the relationship of affect attunement to four factors of development: zygosity, temperament, attachment, and twin preference. Affect attunement occurs when an infant expresses affect and a mother responds cross modally, matching duration, intensity, and rhythm. A sample of 16, same sex, healthy twins (8 MZ, 8 DZ) and their mothers were recruited at 10 to 12 months of age. Monozygous twins attuned at more similar rates than dizygous twins. There was no relationship between attunement, attachment, and temperament, nor between affect signal rate and attunement. Five of eight mothers expressed a twin preference. Eleven of the 16 infants were classified securely attached. Affect attunement is discussed as a measure of the complementarity between an infant's affect signaling rate and a mother's contingent responsiveness. PMID- 2925581 TI - Risk, protective factors, and the prevalence of behavioral and emotional disorders in children and adolescents. AB - The influence of various risk and protective factors on the presence of one or more behavioral or emotional disorders in 3,294 children and adolescents between the ages of 4 and 16 is examined using data from the Ontario Child Health Study conducted in 1983. Multivariate analyses showed that family problems and parental problems heightened the risk for disorder, whereas being a good student, getting along with others, and participation activities reduced the risk of disorder. Some interaction effects between various factors are also reported. The models generated are compared with others reported in the literature. Future research and social policy implications are discussed. PMID- 2925582 TI - Abnormalities of growth in 7- to 18-year-old psychiatric patients. AB - The growth curves of all nonimmigrant school-age children living in one district of Malmo, Sweden and treated at the Department of Child and Youth Psychiatry during 1983 were investigated. The study group consisted of 40 children. Twenty five of these children (63%) showed abnormal growth compared to 6 children (15%) with abnormal growth in an age-and sex-matched nonpsychiatric control population (p less than 0.001). A majority of the children with abnormal growth exhibited deviant growth within the first 4 years of life, usually several years before showing any psychiatric symptoms. These results, if borne out by additional studies, may have important clinical applications in the fields of developmental medicine and child psychiatry. PMID- 2925583 TI - Vulnerability, stress, and resilience in the early development of a high risk child. AB - A young girl at risk for schizophrenia is admitted for inpatient evaluation at age 30 months with growth failure and psychosocial retardation. Her history suggests that adverse environmental experiences, particularly the traumatic loss of primary caregivers around age 15 months, resulted in symptoms consistent with the clinical picture of anaclitic depression and associated psychosocial dwarfism. Intervention in the form of hospitalization and placement by "prescribed" adoption into a favorable caregiving environment produced dramatic recovery in growth and psychological functioning. Follow-up data document sustained positive development 3 1/2 years later. This case illustrates the power of a developmental perspective on psychopathology for conceptualizing and planning treatment for an individual child. PMID- 2925584 TI - A comparison of three nocturnal enuresis treatment methods. AB - To evaluate the efficacy of an operant approach that includes the bell and pad for the treatment of enuresis (Tangible Rewards with Fading), it was compared with an established operant method that includes the bell and pad (the Dry Bed method) and to a conventional Bell and Pad method. Although there were no overall statistically significant differences among the three methods, individual pairwise comparisons were of interest; the Dry Bed method had no advantage, but the Tangible Rewards with Fading method tended to have more patients reach a 14 day dryness criterion (p less than 0.10) and tended to have fewer patients relapse after treatment (p less than 0.08) than the Bell and Pad method. PMID- 2925586 TI - Resolved: child and adolescent psychiatry needs a plan for recertification. PMID- 2925585 TI - Object attachment, thumbsucking, and the passage to sleep. AB - Cross-cultural studies suggest that children who sleep in the same room as their parents and who are breast-fed are less likely to use an attachment object. The present study examined childrearing practices that emphasize physical proximity of parent and child and use of an attachment object and thumbsucking at bedtime with 126 healthy U.S. infants. Four child-rearing practices were focused on: presence or absence of a caregiver when the child actually fell asleep; mode of feeding; location of the child's bed or sleeping place; whether or not the child slept with the parents during the night. Children who had an adult present as they fell asleep were less likely to use an attachment object or suck their thumbs. In contrast to cross-cultural research, the results of the present study suggest that where a child sleeps during the night or how the child is fed is not as important an influence on the bedtime use of an attachment object or thumbsucking as whether an adult is present as the child actually falls asleep. PMID- 2925587 TI - More on sex abuse allegations. PMID- 2925588 TI - PTSD and sexually abused children. PMID- 2925589 TI - More on methylphenidate in autism. PMID- 2925590 TI - Behavioral side-effects of CNS prophylaxis. PMID- 2925591 TI - Our changing field. PMID- 2925592 TI - Nifedipine-haloperidol combination in the treatment of Gilles de la Tourette's syndrome: a case study. AB - Anecdotal case reports have been published describing the use of the calcium channel blockers verapamil and nifedipine to provide rapid and dramatic relief in refractory Gilles de la Tourette's syndrome (TS). The authors' case presentation illustrates that, although these two drugs may not always work alone, they can be successfully used in combination with other medications for treating refractory TS. PMID- 2925593 TI - Sample bias and overinference: two sources of error in interpreting case report data. PMID- 2925594 TI - ECT in children and adolescents. PMID- 2925595 TI - MAOIs in DST nonsuppressors. PMID- 2925596 TI - Dexamethasone suppression test and response to MAOI treatment. PMID- 2925597 TI - Plasma trimipramine levels. PMID- 2925598 TI - Alprazolam treatment of avoidant personality traits in social phobic patients. AB - The authors examined the effect of alprazolam treatment on avoidant personality traits in 14 DSM-III-R social phobics. Six of the nine avoidant traits examined improved with treatment. However, all but one trait (avoiding social or occupational activities requiring interpersonal contact) returned to baseline levels posttreatment. Treatment response and intercorrelation of items indicated two traits that may represent a separate segment of avoidant personality: "No close friends or confidants outside of relatives and family members" and "Exaggerates the potential dangers or risks of everyday situations." PMID- 2925599 TI - A case of immune complex hemolytic anemia, thrombocytopenia, and acute renal failure associated with doxepin use. AB - A 46-year-old man suffering from neurotic depression complicated by alcohol and benzodiazepine dependence developed Coombs'-positive hemolytic anemia and thrombocytopenia with acute renal failure after 5 weeks of monotherapy with doxepin at a final dosage of 100 mg daily. The patient recovered completely after discontinuation of doxepin, blood exchange transfusion, and repeated hemodialyses. He had no history of hematologic abnormalities, exposure to other toxins, or glucose-6-phosphate dehydrogenase deficiency. Because other etiologic factors were ruled out, the short interval between the onset of the patient's hemolytic crisis and the administration of doxepin highly suggests that doxepin was associated with the complication. To the best of our knowledge, ours is the first report of this adverse effect following doxepin administration. PMID- 2925600 TI - Maintenance lithium treatment: side effects and compliance. AB - Fifty-one bipolar patients receiving maintenance lithium treatment were evaluated for the presence of side effects, their degree of distress, and the association of these side effects with compliance. Cognitive side effects and weight gain were the most disturbing to patients, whereas thirst and polyuria were the most common. Self-reported noncompliance correlated most highly with coordination (r = .38, p less than .01) and cognition (r = .30, p less than .05) side effects. Current depressed mood also showed a strong correlation with side effect scores, especially those for cognitive disturbances. However, the correlations between noncompliance and coordination and cognitive side effects were just as strong when the effects of depressed mood were partialled out. These findings indicate the link between noncompliance and lithium-induced central nervous side effects and suggest that related treatment issues must be addressed to ensure maximum clinical response. PMID- 2925602 TI - Poor interrater reliability of MECTA EEG recordings of ECT seizure duration. AB - The electroencephalogram (EEG) tracings of seizure durations recorded by the MECTA SR-1 for 24 patients undergoing right unilateral electroconvulsive therapy (ECT) were estimated independently by four psychiatrists and a neurologist. Differences among raters were often large and, overall, were statistically significant. The literature on interrater reliability for the MECTA EEG remains contradictory, and caution in MECTA EEG use appears warranted. PMID- 2925601 TI - Effects of repeated drug holidays on serum haloperidol concentrations, psychiatric symptoms, and movement disorders in schizophrenic patients. AB - In a crossover experiment the authors investigated the effects of repeated weekly, 2-day, haloperidol drug holidays on serum haloperidol concentrations, mental status, and neuroleptic-induced movement disorders in seven chronic schizophrenic patients. Haloperidol concentrations decreased about 64% during the initial 36 hours of drug holiday and subsequently increased slightly during the next 24 hours of drug holiday. Two-day weekly drug holidays for 6 weeks resulted in an average reduction of 25% in serum haloperidol concentrations at all drug holiday points. Mental status and movement disorders scores, rated by observers blind to the drug-holiday condition, were not significantly affected by drug holidays. PMID- 2925603 TI - Trimipramine-induced neuroleptic malignant syndrome after transient psychogenic polydipsia in one patient. AB - A case of neuroleptic malignant syndrome (NMS) was induced by the antidepressant trimipramine in a 47-year-old woman with obsessive compulsive disorder and major depression. NMS symptoms were associated with a brief episode of polydipsia, and both conditions may have had dopaminergic dysfunction as a common etiology. The patient improved with bromocriptine and dantrolene. PMID- 2925604 TI - Managing antidepressant-induced sweating. PMID- 2925605 TI - Homicidal psychosis during the combined use of cocaine and an over-the-counter cold preparation. PMID- 2925607 TI - Realities of tobacco addiction. PMID- 2925606 TI - Treatable causes of CNS dysfunction in AIDS patients. PMID- 2925608 TI - Cloning and recombinant expression of phospholipase A2 present in rheumatoid arthritic synovial fluid. AB - Synovial fluid from arthritic patients contains multiple forms of phospholipase A2 (PLA2), as resolved by high performance liquid chromatography (Seilhamer, J.J., Plant, S., Pruzanski, W., Schilling, J., Stefanski, E., Vadas, P., and Johnson, L. K. (1989) J. Biochem. (Tokyo), submitted for publication). Here we describe the cloning of a human 4.5-kilobase gene and 800-base pair cDNA encoding the form representing the major peak of activity and protein mass (peak A). The clones encode a mature peptide of 124 amino acids, which follows a prepeptide of 20 residues. The deduced amino acid sequence constitutes an enzyme of the "Type II" class of PLA2s, and resembles PLA2s from other mammalian sources. This represents the first report of a full length mammalian non-pancreatic PLA2 sequence. Active transcription of this PLA2 gene was detected in two different inflammatory cell sources. Recombinant human peak A PLA2 was expressed in vaccinia as a secreted protein which accumulated in conditioned medium. PMID- 2925609 TI - Murine 86- and 84-kDa heat shock proteins, cDNA sequences, chromosome assignments, and evolutionary origins. AB - The two forms of the approximately 90-kDa murine heat shock protein, referred to as HSP86 and HSP84, are coded for by separate but related genes. A full-length nucleotide sequence of the cDNA coding for HSP86 from a chemically induced tumor, Meth A, was determined. Sequences from a number of peptides from HSP86 were found to be in complete agreement with the nucleotide sequence. The HSP84 sequence from the same tumor was also completed. HSP86 and HSP84 are acidic polypeptides 733 and 724 amino acids long with calculated molecular weights of 84,796 and 83,290, respectively. The two proteins are 86% homologous. HSP86 was found to contain internal peptide repeats of Glu-Lys-Glu within a region of highly charged amino acid residues. The coding regions of the cDNAs were 76% homologous; however, this homology did not extend to the 5'- and 3'-untranslated regions. The 5' untranslated region of hsp86 cDNA was considerably longer than that of hsp84 cDNA and, unlike that of hsp84, contained extraneous ATG triplets. Hsp86-related sequences were assigned to chromosomes 12, 11, and 3. An evolutionary tree constructed from HSP90-related protein sequences indicated that HSP86 and HSP84 were likely to have diverged more than 500 million years ago. The findings presented herein suggest that HSP86 and HSP84 may have different functions. PMID- 2925610 TI - Bone marrow-derived mononuclear phagocytes autoregulate mannose receptor expression. AB - This study extends our previous observation that surface mannose receptor expression by pure populations of CSF-1-dependent bone marrow-derived macrophages increases with time (Clohisy, D. R., Bar-Shavit, Z., Chappel, J. C., and Teitelbaum, S. L. (1987) J. Biol. Chem. 262, 15922-15929). We presently find, however, that the progressive enhancement of 125I-mannose-bovine serum albumin (125I-Man-BSA) binding per cell reflects cell number rather than duration of culture. In fact, macrophages plated at high density bind 8-fold more 125I-Man BSA than do their low density counterparts, with no difference in receptor-ligand affinity. Furthermore, cells cultured at high density are ultimately subjected to lower levels of exogenously provided macrophage growth factor, and fewer are in interphase. By obtaining synchronous populations of quiescent bone marrow macrophages, however, we demonstrate that neither cell cycling nor attendant levels of colony stimulating factor-1 influence mannose receptor expression. Our next series of experiments established that density-related mannose receptor expression reflects removal, by marrow macrophages, of a "down-regulating" factor contained in culture medium. To this end, we treated mononuclear phagocytes with either macrophage- or control-conditioned medium and found that, via a fetal calf serum-residing protein(s), only control medium is capable of noncompetitively reducing 125I-Man-BSA binding in a dose-dependent manner. Moreover, reconstituted 20-40% (NH4)2SO4-precipitable fractions derived from either sham-conditioned medium or fetal calf serum are capable of down-regulating mannose receptor expression. Alternatively, the same fraction obtained from macrophage-conditioned medium contains no such activity. Finally, initial characterization of the down regulating factor reveals it to be acid-activable and trypsin-sensitive, yet resistant to heating to at least 80 degrees C, ribonuclease A, or freezing and thawing. We conclude that bone marrow macrophages up-regulate expression of their own plasma membrane mannose receptor by inactivating a noncompetitive, serum residing inhibitory protein(s). PMID- 2925611 TI - Deuterium NMR study of structural and dynamic properties of horseradish peroxidase. AB - High field deuterium NMR spectra have been recorded for various horseradish peroxidase complexes reconstituted with hemins possessing specific 2H labels. The line width of the 2H NMR signals of deuteroheme reconstituted-horseradish peroxidase (HRP) and its cyano complex for the immobilized skeletal 2-2H and 4-2H labels yield the overall protein rotational correlation time (22 ms at 55 degrees C), which is consistent with expectations based on molecular weight. Meso-2H4 labels yield broad (1.3 kHz) signals just upfield from the diamagnetic protein envelope for HRP, and in the central portion of the protein envelope for the CN- ligated resting state HRP. Meso-2H4-labeled mesohemin-reconstituted HRP exhibits a similar signal but shifted further upfield by approximately 10 ppm. The net upfield meso-H hyperfine shifts confirm a five-coordinate structure for resting state HRP. 2Ha resonances for essentially rotationally immobile vinyl groups were detected in both resting state HRP and CN- ligated resting state HRP. Heme methyl 2H-labeling yields relatively narrow lines (approximately 80 Hz) indicative of effective averaging of the quadrupolar relaxation by rapid methyl rotation. Thus the 2H line width of rapidly rotating methyls in hemoproteins can be used effectively to determine the overall protein tumbling rate. Preliminary 2H experiments in meso-2H4-labeled compound I do not support large pi spin density at these positions on the porphyrin cation radical, and argue for a a1u rather than a a2u orbital ground state. PMID- 2925612 TI - Transient kinetics of heparin-catalyzed protease inactivation by antithrombin III. Characterization of assembly, product formation, and heparin dissociation steps in the factor Xa reaction. AB - The kinetics of alpha-factor Xa inhibition by antithrombin III (AT) were studied in the absence and presence of heparin (H) with high affinity for antithrombin by stopped-flow fluorometry at I 0.3, pH 7.4 and 25 degrees C, using the fluorescence probe p-aminobenzamidine (P) and intrinsic protein fluorescence to monitor the reactions. Active site binding of p-aminobenzamidine to factor Xa was characterized by a 200-fold enhancement and 4-nm blue shift of the probe fluorescence emission spectrum (lambda max 372 nm), 29-nm red shift of the excitation spectrum (lambda max 322 nm), and dissociation constant (KD) of about 80 microM. Under pseudo-first order conditions [( AT]0, [H]0, [P]0 much greater than [Xa]0), the observed factor Xa inactivation rate constant (kobs) measured by p-aminobenzamidine displacement or residual enzymatic activity increased linearly with the "effective" antithrombin concentration (i.e. corrected for probe competition) up to 300 microM in the absence of heparin, indicating a simple bimolecular process with a rate constant of 2.1 x 10(3) M-1 s-1. In the presence of heparin, a similar linear dependence of kobs on effective AT.H complex concentration was found up to 25 microM whether the reaction was followed by probe displacement or the quenching of AT.H complex protein fluorescence due to heparin dissociation, consistent with a bimolecular reaction between AT.H complex and free factor Xa with a 300-fold enhanced rate constant of 7 x 10(5) M-1 s-1. Above 25 microM AT.H complex, an increasing dead time displacement of p aminobenzamidine and a downward deviation of kobs from the initial linear dependence on AT.H complex concentration were found, reflecting the saturation of an intermediate Xa.AT.H complex with a KD of 200 microM and a limiting rate of Xa AT product complex formation of 140 s-1. Kinetic studies at catalytic heparin concentrations yielded a kcat/Km for factor Xa at saturating antithrombin of 7 x 10(5) M-1 s-1 in agreement with the bimolecular rate constant obtained in single heparin turnover experiments. These results demonstrate that 1) the accelerating effect of heparin on the AT/Xa reaction is at least partly due to heparin promoting the ordered assembly of antithrombin and factor Xa in an intermediate ternary complex and that 2) heparin catalytic turnover is limited by the rate of conversion of the ternary complex intermediate to the product Xa-AT complex with heparin dissociation occurring either concomitant with this step or in a subsequent faster step. PMID- 2925613 TI - Nonequivalence of the two subunits of horse erythrocyte glutathione transferase in their reaction with sulfhydryl reagents. AB - Glutathione transferase (EC 2.5.1.18) from horse erythrocytes has been purified and some molecular and kinetic properties have been investigated. It appears to be a dimeric protein composed of subunits of about 23 kDa, indistinguishable either in sodium dodecyl sulfate or in urea electrophoresis. Amino acid composition, substrate specificities, sensitivity to inhibitors, CD spectra, and immunological studies provide evidence that the horse enzyme is related to the pi class transferases. This enzyme has only two reactive thiol groups/dimer whose integrity appears to be essential for the activity. A peculiar feature of these protein thiol groups is that they react nonidentically with a number of thiol blocking reagents, i.e. iodacetamide, bromopyruvate, N-ethylmaleimide, and 1 chloro-2,4-dinitrobenzene. Also many disulfides react with one thiol group 5- to 10-fold more rapidly than with the other. The two mixed disulfides so formed also have different rates of reactivation by dithiothreitol. All the structural and kinetic data reported in this paper indicate a nonsymmetrical association of two identical subunits, or alternatively heterodimeric structure with subunits of very similar charge and size. PMID- 2925614 TI - The nicotinamide adenine dinucleotide-binding site of chicken liver xanthine dehydrogenase. Evidence for alteration of the redox potential of the flavin by NAD binding or modification of the NAD-binding site and isolation of a modified peptide. AB - Affinity labeling of the NAD-binding site of chicken liver xanthine dehydrogenase by 5'-p-fluorosulfonylbenzoyladenosine (5'-FSBA) caused spectral perturbation around 450 nm in the same way as NAD. Reductive titration with xanthine of native xanthine dehydrogenase in the presence of NAD showed that redox potentials of the FAD/FADH. and FADH./FADH2 couples were shifted positive by NAD binding to the enzyme. The redox potentials of these couples were also shifted to some extent by modification of the NAD-binding site with 5'-FSBA. These results provide further evidence that binding of NAD to chicken liver xanthine dehydrogenase modulates the reactivity of the enzyme by shifting the redox potential of FAD. Proteolytic cleavage of the [14C]-5'-FSBA-modified enzyme yielded several domain peptides, only one of which contained radioactivity. The isolated radioactive peptide was further digested with Staphylococcus aureus protease and the 14C-labeled peptide was purified by two steps of high performance liquid chromatography. The amino acid sequence of the peptide was determined, and a reactive tyrosine residue was identified. PMID- 2925615 TI - The isolation and primary structure of a 22-kDa extracellular matrix protein from bovine skin. AB - The primary structure of a 22-kDa protein which was isolated during the purification of bovine skin dermatan sulfate proteoglycan is described. The uronate-rich fraction from DEAE-Sepharose chromatography of a 7.8 M urea extract of bovine fetal skin was subjected to gel filtration on Sepharose CL-6B in 4 M guanidine HCl. A prominent component of mass 22 kDa was separated from the proteoglycan and further purified on octyl-Sepharose. The primary structure of this component was determined and found to contain three repeat regions. Each of the three sections contains a similar pattern of looped disulfide bonds. A six amino acid consensus sequence, Asp-Arg-Glx-Trp-Asn/Gln/Lys-Phe/Tyr, is found in each loop. This domain may be involved in associations of the molecule with other extracellular matrix components. PMID- 2925616 TI - Cooperative function of two separate enhancers of the human epidermal growth factor receptor proto-oncogene. AB - Two separate enhancers were identified both upstream and downstream of the promoter of the human epidermal growth factor receptor gene. Transcriptional enhancer activity was found to be associated with a region 1172 and 852 base pairs upstream of the most upstream RNA start site, and within a 530-base pair fragment located in the first intron about 2000 base pairs downstream of the most upstream RNA start site. These two separate enhancers stimulated promoter activity cooperatively in HeLa cells synthesizing the epidermal growth factor receptor. The enhancer downstream of the promoter functioned only in the presence of the other upstream enhancer. Several areas of sequences homology with viral and cellular enhancers were noted in both the upstream and downstream enhancers. The region essential for the downstream enhancer activity has 10 nuclear factor binding sites. PMID- 2925617 TI - The amino acid sequences of the alpha and beta chains of hemoglobin from the snake, Liophis miliaris. AB - The hemoglobin of Liophis miliaris has unusual properties. The hemoglobin is dimeric in the oxy form, and the cooperativity of O2 binding is very low, but both the Bohr effect and cooperativity are greatly enhanced in the presence of ATP (Matsuura, M. S. A., Ogo, S. H., and Focesi, A., Jr. (1987) Comp. Biochem. Physiol. 86A, 683-687). Four unique chains (2 alpha, 2 beta) can be isolated from the hemolysate. The amino acid sequences of one alpha and one beta chain have been determined in an effort to understand the functional properties. Comparison of the sequences with those of the alpha and beta chains of human Hb shows the following. (i) All 7 of the residues in the beta chain normally conserved in globins are identical to those of the human chain: Gly(B6), Phe(CD1), His(E7), Leu(F4), His(F8), Lys(H10), and Tyr(HC2), except that the distal His(E7) has been replaced by Gln in the alpha chain. (ii) All heme contact residues in the beta chain are identical with those in the human chain, but two differences are present in the alpha chain: the distal His(E7) is replaced by Gln and Met(B13) by Leu. (iii) All residues that form the binding site for organic phosphates are identical to those in human Hb. (iv) The major residues that contribute to the normal Bohr effect in human Hb, Asp-beta 94, His-beta 146, and Val-alpha 1 are conserved. (v) All beta chain residues at the alpha 1 beta 2 interface are identical with those in the human chain except two: Glu(G3)----Val and Glu(CD2)-- -Thr; these differences in charged residues may explain the dissociation to dimers. (vi) The 23 residues of the alpha chain in the alpha 1 beta 2 contact region are identical with those of the human chain except three: Phe(B14)----Leu, Thr(C3)----Gln and Pro(CD2)----Ser. (vii) A total of 17 differences occur at the alpha 1 beta 1 interface, 11 in the alpha chain and 6 in the beta chain. PMID- 2925618 TI - Primary structure of chicken pituitary prolactin deduced from the cDNA sequence. Conserved and specific amino acid residues in the domains of the prolactins. AB - The perform of chicken prolactin (PRL) deduced from the cDNA sequence contains a signal peptide of 30 amino acid residues followed by a mature PRL of 199 residues. Chicken PRL shows 77, 68, 67, 58, and 31% identity of amino acid sequence with whale, human, ovine, rat, and salmon PRLs, respectively. Elucidation of the primary structure of avian PRL enabled extended analysis of the specific and conserved amino acid residues and domains of the PRL molecules. The mammalian, teleostean, and avian PRLs share 32 common residues, and these conserved residues are observed to cluster in four distinct domains (PD1 to PD4), corresponding to four of five conserved domains of the growth hormones. Of the 32 residues, 8 residues in the PD2 and PD4 domains, including 4 cysteines, are conserved by other members of the growth hormone family, which indicates that these 8 residues may be essential for common structural features of the gene family. On the other hand, 13 other residues distributed among all four domains are conserved almost exclusively in the PRLs, suggesting that these residues are indispensable for specific binding of the PRLs to their receptors. PMID- 2925619 TI - Photoaffinity labeling of the lumenal K+ site of the gastric (H+ + K+)-ATPase. AB - A photoaffinity label for the lumenal K+ site of the gastric (H+ + K+)-ATPase has been identified. Seven azido derivatives based upon the reversible K+ site inhibitor SCH 28080 were studied, one of which, m-ATIP (8-(3-azidophenylmethoxy) 1,2,3-trimethylimidazo[1,2-a] pyridinium iodide), was subsequently synthesized in radiolabeled form. In the absence of UV irradiation, m-ATIP inhibited K+ stimulated ATPase activity in lyophilized gastric vesicles competitively with respect to K+, with a Ki value of 2.4 microM at pH 7.0. Irradiation of lyophilized gastric vesicles at pH 7.0 with [14C]m-ATIP in the presence of 0.2 mM ATP resulted in a time-dependent inactivation of ATPase activity that was associated with an incorporation of radioactivity into a 100-kDa polypeptide representing the catalytic subunit of the (H+ + K+)-ATPase. Both inactivation and incorporation were blocked in the presence of 10 mM KCl but not with 10 mM NaCl, consistent with interaction at the K+ site. The level of incorporation required to produce complete inhibition of ATPase activity was 1.9 +/- 0.2 times the number of catalytic phosphorylation sites in the same preparation. Tryptic digestion of gastric vesicle membranes, labeled with [14C]m-ATIP, failed to release the radioactivity from the membranes suggesting that the site of interaction was close to or within the membrane-spanning sections of this ion pump. PMID- 2925620 TI - Studies on the NADPH oxidase of phagocytes. Production of a monoclonal antibody which blocks the enzymatic activity of pig neutrophil NADPH oxidase. AB - We describe in this paper a monoclonal antibody to pig NADPH oxidase which inhibits enzymatic activity. This antibody, designated 1H8.2, was selected from a group of monoclonal antibodies produced against active preparations of purified NADPH oxidase and which showed selectivity of binding. 1H8.2 is an IgM restricted in binding to pig NADPH oxidase and showing higher binding to NADPH oxidase purified from phorbol myristate acetate-stimulated than from resting neutrophils. The antibody inhibits by about 90% the oxidase activity at 20-50 micrograms/ml. Inhibition is due to a decrease of the Vmax of the oxidase, and the Km is not affected. Incubation of the NADPH oxidase with 1H8.2 in the presence of concentrations of NADPH up to 25-fold the Km does not prevent the inhibition. Together with the evidence that the antibody does not inhibit the neutrophil superoxide dismutase-insensitive NADPH cytochrome c reductase and the liver NADPH cytochrome c reductase this observation indicates that the 1H8.2 does not bind to an epitope belonging to the NADPH-binding site. Experiments of immunoprecipitation of iodinated membrane proteins and of immunoaffinity purification showed that 1H8.2 recognizes a heterodimer of apparent molecular mass of 16/18 and 14 kDa. These polypeptides can be involved in the NADPH oxidase activity or represent still unrecognized molecules able to modulate its function. PMID- 2925621 TI - The major surface antigen, P30, of Toxoplasma gondii is anchored by a glycolipid. AB - P30, the major surface antigen of the parasitic protozoan Toxoplasma gondii, can be specifically labeled with [3H]palmitic acid and with myo-[2-3H]inositol. The fatty acid label can be released by treatment of P30 with phosphatidylinositol specific phospholipase C (PI-PLC). Such treatment exposes an immunological "cross reacting determinant" first described on Trypanosoma brucei variant surface glycoprotein. PI-PLC cleavage of intact parasites metabolically labeled with [35S]methionine results in the release of intact P30 polypeptide in a form which migrates faster in polyacrylamide gel electrophoresis. These results argue that P30 is anchored by a glycolipid. Results from thin layer chromatography analysis of purified [3H] palmitate-labeled P30 treated with PI-PLC, together with susceptibility to mild alkali hydrolysis and to cleavage with phospholipase A2, suggest that the glycolipid anchor of T. gondii P30 includes a 1,2-diacylglycerol moiety. PMID- 2925622 TI - Dehydrogenase-dependent ethanol metabolism in deer mice (Peromyscus maniculatus) lacking cytosolic alcohol dehydrogenase. Reversibility and isotope effects in vivo and in subcellular fractions. AB - Elimination of [2H]ethanol in vivo as studied by gas chromatography/mass spectrometry occurred at about half the rate in deer mice reported to lack alcohol dehydrogenase (ADH-) compared with ADH+ deer mice and exhibited kinetic isotope effects on Vmax and Km (D(V/K] of 2.2 +/- 0.1 and 3.2 +/- 0.8 in the two strains, respectively. To an equal extent in both strains, ethanol elimination was accompanied by an ethanol-acetaldehyde exchange with an intermolecular transfer of hydrogen atoms, indicating the occurrence of dehydrogenase activity. This exchange was also observed in perfused deer mouse livers. Based on calculations it was estimated that at least 50% of ethanol elimination in ADH- deer mice was caused by the action of dehydrogenase systems. NADPH-supported cytochrome P-450-dependent ethanol oxidation in liver microsomes from ADH+ and ADH- deer mice was not stereoselective and occurred with a D(V/K) of 3.6. The D(V/K) value of catalase-dependent oxidation was 1.8, whereas a kinetic isotope effect of cytosolic ADH in the ADH+ strain was 3.2. Mitochondria from both ADH+ and ADH- deer mice catalyzed NAD+-dependent ethanol oxidation and NADH-dependent acetaldehyde reduction. The kinetic isotope effects of NAD+-dependent ethanol oxidation in the mitochondrial fraction from ADH+ and ADH- deer mice were 2.0 +/- 0.1 and 2.3 +/- 0.3, respectively. The results indicate only a minor contribution by cytochrome P-450 to ethanol elimination, whereas the isotope effects are consistent with ethanol oxidation by the catalase-H2O2 system in ADH- deer mice in addition to the dehydrogenase systems. PMID- 2925623 TI - Reactions of anthranilate hydroxylase with salicylate, a nonhydroxylated substrate analogue. Steady state and rapid reaction kinetics. AB - Steady state and rapid reaction kinetics of the flavoprotein anthranilate hydroxylase (EC 1.14.12.2) have been examined with the nonhydroxylated substrate analogue, salicylate. Since the reaction with salicylate does not involve events in which aromatic substrate is oxygenated, it provides a simpler model for studying the hysteresis exhibited by this enzyme. It is shown that the first turnover of the enzyme is slower than subsequent turnovers owing in part to slow initial binding reactions of salicylate with the enzyme. The reductive half reaction of the first turnover is also slow since rapid reduction of the enzyme flavin requires bound aromatic substrate. The oxidative half-reaction involves reaction of the reduced enzyme-salicylate complex with oxygen to form a flavin C4a-hydroperoxide, which then decays to oxidized flavoenzyme and H2O2. Several lines of evidence indicate that salicylate remains bound to the enzyme at the end of the catalytic cycle so that in turnovers subsequent to the first, the slow steps involving salicylate binding are avoided. PMID- 2925624 TI - Cytosolic free magnesium levels in ischemic rat heart. AB - Changes in cytosolic free magnesium ion concentration (Mgi) during myocardial ischemia were measured by 19F NMR in perfused rat hearts loaded with fluorine labeled derivatives of the magnesium chelator o-aminophenol-N,N,O-triacetate. The perfused rat hearts were loaded intracellularly with the appropriate magnesium indicator by perfusion with 200-400 ml of Krebs-Henseleit buffer containing 5 microM acetoxymethyl ester of the indicator. Basal Mgi concentrations measured by three different indicators averaged 0.85 +/- 0.10 mM (n = 9) and showed no correlation with the KD of the indicator used. 31P NMR measurements of the magnesium-dependent shift between alpha- and beta-phosphates of ATP demonstrate that there is no measurable lowering of Mgi during loading with fluorinated o aminophenol-N,N,O-triacetate. Between 10 and 15 min of ischemia, Mgi rose nearly 3-fold to 2.1 +/- 0.4 mM. This increase in Mgi occurred over the same time course as the decrease in ATP. After 20 min of reperfusion with Krebs-Henseleit buffer, Mgi declined to 1.5 +/- 0.5 mM. This sustained elevation of Mgi above basal levels may inhibit calcium release from sarcoplasmic reticulum, thereby contributing to the well documented impairment of mechanical function that occurs after a reversible period of ischemia. PMID- 2925625 TI - Diethylstilbestrol metabolites and analogs. Stereochemical probes for the estrogen receptor binding site. AB - Indenestrol A (IA) and indenestrol B (IB) are analogs and metabolites of diethylstilbestrol (DES). These compounds have high binding affinity with the estrogen receptor (ER) but possess weak uterotropic activity. Due to their chemical structures, IA and IB exist as mixtures of enantiomers. We investigated whether the poor biological activity of these compounds was due to differential activity of the enantiomers. We also utilized these compounds as probes to determine the extent of stereochemical sensitivity in the ER ligand binding site. The IA and IB enantiomers were separated to greater than 98% purity using a chiral high pressure liquid chromatography column. Their enantiomeric nature was confirmed by mass spectrometry and NMR. The purified IA enantiomer peak 1 was derivatized with 4-bromobenzoyl chloride. The resulting di(4-bronobenzoate) IA was analyzed by x-ray crystallography and the absolute enantiomeric conformation assigned is C(3)-R. The IA enantiomers designated IA-R and A-S were assayed by competitive binding to cytosolic ER. The competitive binding index was estradiol, 100; DES, 286; IA-Rac (racemic mixture of IA), 143; IA-R, 3; and IA-S, 285; the index showed that ER demonstrates a stereochemical chiral preference. The IB enantiomers did not show a binding preference: IB, 145; IB-1, 100; and IB-2, 143. The differences in the IA enantiomer binding were shown to be due to competitive interactions by Lineweaver-Burk analysis of saturation binding of estradiol to ER in the presence of 1-, 5-, and 10-fold molar excess of competitor. Differences in binding affinity of the enantiomers could be partially explained by differences in the association rate constant (k+1) determined by association rate inhibition studies in which IA-S was 15 times more active than IA-R. Nuclear estrogen receptor levels were measured 1 h after in vivo treatment with doses of 5-20 micrograms/kg. The IA-Rac produced only 60% of the levels is compared with DES. Nuclear ER levels were checked every 30 min up to 2 h with no apparent difference, indicating that the low early levels were not due to a delayed estrogen receptor retention. When the enantiomers were tested individually only a dose of 10 micrograms/kg IA-S translocated ER to a level comparable to DES, while IA-R showed low levels at several doses. These results suggest that the poor biological activity of IA may be related to the differential ER interaction of its enantiomers.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2925626 TI - The interactions of bilirubin with model and biological membranes. AB - The partitioning of bilirubin between albumin and model and biological membranes and the differential partitioning of bilirubin between membranes with different lipid and protein compositions were measured. Partition coefficients were independent of the concentration of bilirubin in membranes up to at least 7 mol of bilirubin/mol of phospholipid. The avidity of albumin for bilirubin was greater than that of membranes, but the avidity of the latter for bilirubin depended on the composition of the membrane. Bilirubin partitioned preferentially into model membranes comprised of microsomal lipids greater than dioleoylphosphatidylcholine = plasma membrane lipids much greater than egg phosphatidylcholine = dimyristoylphosphatidylcholine. Partitioning into membranes was increased if these contained proteins, but the effect of proteins could not be attributed to specific binding to sites on proteins, as reflected by the temperature independence of partition coefficients. Differential partitioning of bilirubin into different membranes of pure lipids also was independent of temperature. Differences in the bulk phase fluidity of membranes does not appear to account for the preferential partitioning of bilirubin into some membranes. It appears that bilirubin partitions into elements of free volume of differing sizes in membranes with variable lipid compositions and that the size of these elements can be increased by adding proteins to membranes. PMID- 2925627 TI - Modulation of nuclear matrix-associated 2',5'-oligoadenylate metabolism and ribonuclease L activity in H9 cells by human immunodeficiency virus. AB - Human T cells (H9), infected with the HTLV-IIIB strain of the human immunodeficiency virus (HIV-1), have been used to study the alteration of 2',5' oligoadenylate [2'-5')A) metabolism in relation to virus production. The synthesis of (2'-5')A was determined to proceed in close association with the nuclear matrix. After HIV infection the (2'-5')A synthetase activity increased from 1.1 to 1.5 pmol of (2'-5')A synthesized/100 micrograms of nuclear matrix protein (during a 3-h in vitro incubation period) to 8.2 pmol at day 3 after infection. Then the activity dropped to the initial values. In non-infected H9 cells the (2'-5')A synthetase activity remained unchanged. Simultaneously with the decrease of the (2'-5')A level the cells started to release HIV. At the time of maximum synthetase levels the (2'-5')A-activated endoribonuclease (RNase L) activity strongly increased. Only one protein could be selectively cross-linked to a (2'-5')A derivative in the nuclear matrix from H9 cells; this protein is assumed to be RNase L. Experimental evidence is provided revealing that RNase L degrades HIV transcripts. A correlation could be established between high levels of (2'-5')A and RNase L and a failure of the cells to release HIV. 3'-Azido-3' deoxythymidine was shown to cause an extension of the time period during which an RNase L-mediated degradation of viral transcripts occurred. The possibility of a novel molecular pharmacologic approach on the level of (2'-5')A metabolism is discussed. PMID- 2925628 TI - Studies on the intoxication pathway of tetanus toxin in the rat pheochromocytoma (PC12) cell line. Binding, internalization, and inhibition of acetylcholine release. AB - Tetanus toxin was found to be a potent inhibitor of neurosecretion in the rat pheochromocytoma cell line PC12, a system in which biochemical and functional studies could be performed in parallel. Incubation of the cells with 10 nM tetanus toxin (3 h) led to an inhibition of acetylcholine release by 75-80% when evoked by 200 microM veratridine, 1 mM carbachol, or 2 mM Ba2+. The main characteristics of the inhibition process are: 1) the toxin is very potent, with threshold doses of 10 pM; 2) the action of toxin is blocked at low temperature (0 degrees C) and by antitoxin; 3) the effects are dose- and time-dependent; 4) a concentration-dependent lag phase precedes the onset of the inhibitory effects. Thus the PC12 cultures are a valid system for studies on the underlying molecular process in tetanus action. This system was exploited by the use of long term incubation studies to examine the processes responsible for the lag phase. When cells were incubated with 0.1 nM 125I-tetanus toxin, cell-associated toxin reached a plateau of 16 fmol of toxin/mg of protein, yet the toxic effects did not appear until 12 h. Further, PC12 cells were found to rapidly internalize tetanus toxin, with a half-life of 1-2 min, once it was bound to the surface of the cells. Thus, the lag phase results from steps that occur in the intracellular compartment after internalization. An important discovery was that the differentiation state of the PC12 cells was a critical factor in determining sensitivity to tetanus toxin. Cells that were cultured with nerve growth factor for 8-12 days were very sensitive to toxin. In contrast, acetylcholine release from nondifferentiated, autodifferentiated, or dexamethasone-treated cultures was insensitive to tetanus toxin. Since differential expression of high affinity tetanus toxin receptors cannot explain these results, it is concluded that PC12 cells are capable of expressing different forms of excitation-secretion coupling mechanisms. Tetanus toxin should prove a valuable probe to further distinguish these processes. PMID- 2925629 TI - Nitric oxide and nitrous oxide production and cycling during dissimilatory nitrite reduction by Pseudomonas perfectomarina. AB - The denitrifier Pseudomonas perfectomarina reduced nitrite under conditions of kinetic competition between cells and gas sparging for extracellular dissolved nitric and nitrous oxides, NOaq and N2Oaq, in a chemically defined marine medium. Time courses of nitrite reduction and NOg and N2Og alpha removal were integrated to give NOg and N2Og yields. At high sparging rates, the NOg yield was greater than 50% of nitrite-N reduced, and the yield of NOg + N2Og was approximately 75%. Hence interrupted denitrification yields NOaq and N2Oaq as major products. The yields varied with sparging rates in agreement with a quantitative model of denitrification (Betlach, M. P., and Tiedje, J.M. (1981) Appl. Environ. Microbiol. 42, 1074-1084) that applies simplified Michaelis-Menten kinetics to NO2-----NOaq----N2Oaq----N2. The fit gave an estimate of the maximum scavengeable NOaq yield of 73 +/- 8% of nitrite-N. Thus a minor path independent of NOaq is also required. The fit of the model to data at lower sparging rates, where normal denitrification products predominate, implies that the extracellular NOaq pool yield is independent of gas sparging rate. Thus in P. perfectomarina NOaq and N2Oaq are intermediates, or facilely equilibrate with true intermediates, during complete denitrification. The recovery of most nitrite-N as NO and/or N2O under perturbed conditions is not an artifact of irreversible product removal, but an attribute of denitrification in this species, and most probably it is characteristic of denitrification in other species as well. PMID- 2925630 TI - Comparison of pregnenolone synthesis by cytochrome P-450scc in mitochondria from porcine corpora lutea and granulosa cells of follicles. AB - Substrate turnover rates by cytochrome P-450scc were measured in mitochondria isolated from corpora lutea and granulosa cells of follicles. Hydroxycholesterol substrates were added to the mitochondria to test the degree of saturation of the cytochrome with endogenous cholesterol during pregnenolone synthesis. 25 Hydroxycholesterol proved unsuitable for this since it was converted into pregnenolone with a maximum velocity of only 25% of that for cholesterol. 20 alpha-Hydroxycholesterol was found to be suitable providing correction was made for the one less hydroxylation required to convert this substrate into pregnenolone, compared to cholesterol. Mitochondria isolated from large follicles and corpora lutea displayed biphasic time courses for pregnenolone synthesis from endogenous cholesterol with a rapid phase lasting for 2-4 min and a slow phase which was linear for at least 30 min. Only a single rapid phase was observed for these mitochondria in the presence of 20 alpha-hydroxycholesterol. From the degree of stimulation of the substrate turnover rate by this steroid, it was concluded that the endogenous cholesterol concentration was saturating during the fast phase for large follicles but subsaturating in luteal mitochondria. Time courses for pregnenolone synthesis by mitochondria isolated from granulosa cells of small and medium follicles were linear for 30 min and gave a substrate turnover rate of 16-18 mol of steroid/min/mol of cytochrome P-450scc, similar to the turnover rates under saturating substrate conditions determined for large follicles and corpora lutea. The substrate turnover rate for cytochrome P-450scc in medium follicles was not increased by the addition of 20 alpha hydroxycholesterol, indicating that the cholesterol concentration in the steroidogenic pool of these mitochondria was saturating and remained so over the 30-min duration of the incubation. It is therefore unlikely that gonadotropin stimulation of granulosa cells of small to medium follicles could acutely regulate pregnenolone synthesis by increasing the rate of transfer of cholesterol into a steroidogenic pool. This study shows that as the cytochrome P-450scc concentration in porcine ovarian mitochondria increases during follicular growth and luteinization there is a decrease in the fractional saturation of the cytochrome with cholesterol. PMID- 2925631 TI - The effect of interspecies transfer of Rhizobium host-specific nodulation genes on acidic polysaccharide structure and in situ binding by host lectin. AB - Host specificity in the Rhizobium-legume symbiosis is controlled in the bacterium by host specific nodulation (hsn) genes residing on its symbiotic plasmid. We have examined the structure of the major acidic heteropolysaccharide produced by recombinant hybrid strains of Rhizobium leguminosarum carrying cloned R. trifolii hsn genes with those produced by the parent donor and recipient strains. Alteration of the nod gene composition of R. leguminosarum strain 300 by introduction of an 8-kilobase set of hsn genes (nodFERL and nodMN) from R. trifolii strain ANU843, resulted in a hybrid strain which conferred efficient white clover infection and nodulation, production of the R. trifolii-type acidic polysaccharide, and an increased proportion of bacterial cells which bound to the white clover lectin, trifoliin A, in the external root environment. 1H NMR studies indicated that the structure of the polysaccharide from the hybrid recombinant differed from that of the R. leguminosarum strain 300 recipient in site and stoichiometry of acetate and stoichiometry of 3-hydroxybutyrate substituents. In contrast, the polysaccharide from a different hybrid recombinant strain containing only R. trifolii nodFERL genes had the acetylation pattern of the R. leguminosarum recipient but was substituted with 3-hydroxybutyrate at a level between that made by R. trifolii and R. leguminosarum. This latter recombinant strain displays sparse infection and nodulation of white clover roots. Immunofluorescence studies indicated that the R. leguminosarum recombinant strain containing the full complement of R. trifolii hsn genes (nodFERL and nodMN) gained the ability to interact with the excreted lectin, trifoliin A, in the white clover root environment, whereas the recombinant strain containing R. trifolii nodFERL only, was significantly attenuated in this cell-lectin interaction. These results indicate that the acylation pattern of the acidic polysaccharide synthesized by these hybrid recombinants of R. leguminosarum is influenced by the introduced hsn genes of R. trifolii and suggest that the acidic polysaccharide of R. trifolii and the interaction of these bacteria with the host lectin may contribute to host specificity in the white clover-R. trifolii symbiosis. PMID- 2925632 TI - Conversion of domains into subunits in the processing of egg yolk biotin-binding protein I. AB - Biotin-binding protein I (BBP-I), a protein that differs in its heat stability at low concentrations from that of BBP-II, has been purified from the yolk of hen oocytes and compared to BBP-II. Rabbit antiserum to BBP-II cross-reacts with identity to BBP-I. The molecular mass of BBP-I under denaturing conditions is about 68 kDa, a value four times that of BBP-II. Limited trypsin proteolysis of BBP-I generates subunits of 18 kDa with intermediate forms of approximately 51 and 34 kDa. The NH2-terminal sequence of BBP-I is very similar to that of BBP-II but has little of the polymorphism that is presumed to be generated at several positions by the slightly different subunits of BBP-II. These results indicate an unusual processing pathway in which four tandemly repeated biotin-binding domains of BBP-I become the subunits of BBP-II after limited proteolysis. PMID- 2925633 TI - Structure and properties of a human non-pancreatic phospholipase A2. AB - We have purified a human non-pancreatic phospholipase A2 that is present in platelets and is enriched in rheumatoid synovial fluid. The enzyme is calcium dependent, has a pH optimum of 8-10, and shows a striking preference for substrate presented in the form of Escherichia coli membranes. In the E. coli phospholipase A2 assay the phospholipase exhibits an apparent specific activity of 300 mumol/mg/min. Using oligonucleotide probes based on amino-terminal sequence data, we cloned the corresponding human gene from a genomic DNA library and expressed the gene in animal cells. The protein was secreted from the cells in an active form. The deduced amino acid sequence of the human protein consists of 124 amino acids, contains structural features common to all known phospholipase A2s, and has a half-cystine pattern that is characteristic of the snake venom group II enzymes. PMID- 2925634 TI - The expression of alpha(1)-acid glycoprotein mRNA during rat development. High levels of expression in the decidua. AB - During the acute phase response to inflammation the plasma concentration of some proteins, such as alpha(1-acid glycoprotein (AGP), increases dramatically. Since breakdown and remodeling of tissue is common to both nidation and inflammation we studied the tissue distribution and regulation of AGP mRNA levels during the embryonic development of the rat. High levels of mRNA coding for AGP were detected in the placenta during early fetal development. Expression of this mRNA was confined to the decidua and was first observed approximately 1 day after implantation when proliferation of the decidua is already well advanced. Maximum levels were attained about 5 days after implantation, after which the levels decreased rapidly. In contrast to the high levels of AGP mRNA in the decidua only very low levels were detected in fetal liver and visceral yolk sac, and there was only a small increase in the levels in maternal liver. Corticosteroid hormone responsiveness of AGP mRNA synthesis by hepatocytes appeared 3 days before birth. It is likely that the synthesis of AGP by the cells of the decidua is important in establishing the precisely controlled interaction between mother and embryo during nidation. PMID- 2925635 TI - Enzymic conversion of 11,12-leukotriene A4 to 11,12-dihydroxy-5,14-cis-7,9-trans eicosatetraenoic acid. Purification of an epoxide hydrolase from the guinea pig liver cytosol. AB - (11S,12S)-Epoxy-5,14-cis-7,9-trans-eicosatetraenoic acid (11,12-leukotriene A4) was nonenzymically converted to seven compounds: two diastereomers of (12S) hydroxyeicosatetraeno-delta-lactones (major products), two diastereomers of (5,12S)-dihydroxyeicosatetraenoic acid and three stereoisomers of (11,12S) dihydroxyeicosatetraenoic acid. Among these compounds, (11R,12S)-dihydroxy-5,14 cis-7,9-trans-eicosatetraenoic acid proved to be the only enzymic product. This hydrolysis activity was present in the cytosol fractions of various tissues of guinea pig such as liver, adrenal gland, small intestine, and brain. We purified the epoxide hydrolase to an apparent homogeneity from the guinea pig liver. The enzyme had a molecular weight of 60,000 as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis, and an isoelectric point of 7.3. The partial amino acid sequence was different from that of the microsomal enzyme. Km and Vmax values for 11,12-leukotriene A4 were 18 microM and 2.4 mumol/min/mg protein, respectively. These results indicate that 11,12-dihydroxyeicosatetraenoic acid is enzymically synthesized from 11,12-leukotriene A4 by the action of the cytosolic epoxide hydrolase in vitro. PMID- 2925636 TI - Developmental regulation of peptidylglycine alpha-amidating monooxygenase (PAM) in rat heart atrium and ventricle. Tissue-specific changes in distribution of PAM activity, mRNA levels, and protein forms. AB - The high levels of peptidylglycine alpha-amidating monooxygenase (PAM, EC 1.14.17.3) found in adult rat atrium led us to examine PAM expression in rat atrium and ventricle from embryonic day 14 through adulthood. Immunocytochemical studies using antisera to PAM identified cardiocytes as the major site of PAM expression in atrium and ventricle throughout development. Levels of PAM mRNA and PAM activity exhibited distinctly different developmental profiles in atrium and ventricle. Ventricular PAM mRNA and PAM activity were highest from embryonic days 14 through 18, declined at the time of birth, rose slightly during the first postnatal week, and declined toward adult levels. Atrial PAM mRNA and PAM activity were low at embryonic day 14, rose to a peak immediately before birth, declined at the time of birth, and then rose after birth. Levels of atrial PAM mRNA and PAM activity were not directly correlated at all developmental stages. Two major forms of PAM mRNA (4.2 +/- 0.1 and 3.8 +/- 0.1 kilobase(s] were identified in atrium and ventricle throughout development. The prevalence of the two forms varied with developmental stage, with atrium and ventricle containing similar forms at each stage. Western blots of atrial and ventricular membranes revealed the existence of a developmental stage-specific distribution of PAM protein among forms ranging in mass from 125 to 94 kDa. In both atrium and ventricle PAM activity was primarily soluble from embryonic days 14 through 16 and primarily particulate after birth. The role of PAM in the heart is not yet clear, but the presence of tissue-specific and developmentally regulated alterations in PAM mRNA, PAM protein, and PAM activity suggests that this peptide processing enzyme plays a key role in the heart. PMID- 2925637 TI - Chemical synthesis and enzymic processing of precursor forms of cecropins A and B. AB - Radiolabeled preprocecropin B, with an alpha-amidated COOH terminus, and preprocecropin A, extended at the COOH terminus by a glycine residue, were synthesized by solid-phase methods. The respective syntheses were interrupted at intervals to allow the preparation of the predicted procecropins A and B as well as three other truncated derivatives of the cecropin A precursors. All the synthetic peptides were purified to near homogeneity by reverse-phase liquid chromatography and their purity was established by analytical high performance liquid chromatography, gel electrophoresis, and amino acid analysis. A dipeptidyl aminopeptidase was purified about 350 times from the hemolymph of cecropia pupae and characterized by its affinity for different substrates and inhibitors. The synthetic prepro peptides were tested for processing by an extract of dog pancreas microsomes and purified leader peptidase from Escherichia coli, with and without partly purified dipeptidyl aminopeptidase, and the two synthetic proforms were also processed with the dipeptidyl aminopeptidase alone. From these experiments we conclude that the signal/leader peptidase cleaves the peptide bond between Ala-5 and Ala-4. This cleavage site is further substantiated by radio sequencing of procecropin A isolated after synthesis in a coupled system for in vitro transcription, translation, and processing. The two procecropins, which are stable to further digestion by the signal peptidase, are further processed by dipeptidyl aminopeptidase which removes, in two steps, the dipeptides Ala-Pro (residues -4 and -3) and Glu-Pro (residues -2 and -1). Although the synthetic peptide with only one dipeptide (Glu-Pro) preceding the mature cecropin sequence could function as a substrate for dipeptidyl aminopeptidase, it could be demonstrated as an intermediate in the enzymatic reaction with the procecropins. Dipeptidyl aminopoptidase did not cleave the procecropin analog when it was preceded by a single alanine residue, i.e. preprocecropin (-5,38). Antibacterial activity was demonstrated for the mature cecropin A-Gly obtained by processing of the synthetic preproprotein. PMID- 2925638 TI - Phosphorylation of threonyl- and seryl-tRNA synthetase by cAMP-dependent protein kinase. A possible role in the regulation of P1, P4-bis(5'-adenosyl) tetraphosphate (Ap4A) synthesis. AB - Threonyl-tRNA synthetase has been shown to be phosphorylated in reticulocytes (Dang, C. V., Tan, E. M., and Traugh, J. A., (1988) FASEB J. 2, 2376-2379). Upon incubation of reticulocytes with 8-bromo-cAMP, phosphorylation of threonyl-tRNA synthetase is stimulated approximately 2-fold, an increase similar to that observed with ribosomal protein S6. To analyze the effects of phosphorylation on activity, threonyl-tRNA synthetase has been purified to apparent homogeneity from rabbit reticulocytes utilizing a four-step purification procedure with the simultaneous purification of seryl-tRNA synthetase. Both synthetases are phosphorylated in vitro by the cAMP-dependent protein kinase. Prior to phosphorylation, the two synthetases produce significant amounts of P1, P4-bis(5' adenosyl)-tetraphosphate (Ap4A) in the presence of the cognate amino acid and ATP, with activities comparable to that of lysyl-tRNA synthetase. Phosphorylation has no effect on aminoacylation, but an increase in Ap4A synthesis of up to 6 fold is observed with threonyl-tRNA synthetase and 2-fold with seryl-tRNA synthetase. Thus, cAMP-mediated phosphorylation of specific aminoacyl-tRNA synthetases appears to be a potential mode of regulation of Ap4A synthesis in mammals. PMID- 2925639 TI - 1-O-hexadecyl-2-Q-methylglycerol, a novel inhibitor of protein kinase C, inhibits the respiratory burst in human neutrophils. AB - To assess the role of protein kinase C (Ca2+/phospholipid-dependent enzyme) in the activation of the human neutrophil respiratory burst, we have utilized an ether lipid of the type 1-O-alkyl-2-O-methylglycerol (AMG), recently shown to be an inhibitor of this kinase. AMG-C16 (with an hexadecyl chain at the sn-1 position) was found to inhibit the respiratory burst induced by sub-optimal concentrations of phorbol 12,13-dibutyrate. Respiratory burst activity was recovered by subsequent addition of a supraoptimal dose of phorbol 12-myristate 13-acetate, indicating that in the presence of the inhibitor only the activation of the NADPH:O2 oxidoreductase via protein kinase C is inhibited, but not the oxidoreductase itself. The respiratory burst induced by the chemoattractant N formyl-methionyl-leucyl-phenylalanine (fMLP) was also inhibited in the presence of AMG-C16, the extent of inhibition being dependent on the concentration of fMLP. At the concentrations applied in these studies, AMG-C16 had no effect on cell viability, did not affect the formation of inositol phosphates induced by fMLP, and did not affect the characteristics of the Ca2+ fluxes induced by the same stimulus. In a cell-free assay system, AMG-C16 had no effect on the activity of cAMP-dependent or Ca2+/calmodulin-dependent protein kinase but inhibited protein kinase C in a dose-dependent fashion. To characterize the inhibitory action of AMG-C16 on the respiratory burst activity in more detail, we studied protein phosphorylation in relation to respiratory burst activity in neutrophil cytoplasts. We focused on the phosphorylation of the 47-kDa protein, because this protein is functionally associated with the NADPH:O2 oxidoreductase. At suboptimal concentrations of phorbol 12,13-dibutyrate, AMG-C16 inhibited phosphorylation of proteins, including that of the 47-kDa protein. Recovery of protein phosphorylation in parallel to recovery of respiratory burst activity was obtained by addition of increasing doses of phorbol 12,13-dibutyrate. Recovery of respiratory burst activity at intermediate concentrations of fMLP did not result in a proportional increase in 47-kDa protein phosphorylation; phosphorylation of the 47-kDa protein was recovered only at high concentrations of fMLP. From these data we conclude that protein kinase C is involved in the activation of the respiratory burst by phorbol esters and fMLP. However, with fMLP as a stimulus, a second signal seems to be triggered, which is insensitive to AMG-C16. PMID- 2925640 TI - Sequence-targeted cleavage of single- and double-stranded DNA by oligothymidylates covalently linked to 1,10-phenanthroline. AB - The nuclease activity of 1,10-phenanthroline copper ion was targeted to a specific sequence by attachment of the ligand to the 5' or 3' end of octathymidylates. An acridine derivative was also attached to the other end of the oligothymidylate-phenanthroline conjugate. The duplex formed by the oligothymidylate with its complementary sequence was stabilized by intercalation of the acridine derivative. The reaction induced by 3-mercaptopropionic acid led to a very localized cleavage of a 27-nucleotide-long DNA fragment containing a (dA)8 sequence. At high NaCl concentration or in the presence of spermine, cleavage of the single-stranded 27-mer fragment occurred on both sides of the target sequence. This was ascribed to the formation of a triple helix involving two 1,10-phenanthroline-octathymidylate strands that adopt an antiparallel orientation with respect to each other. When a 27-mer duplex was used as a substrate, cleavage sites were observed on both strands. The location of the cleavage sites led us to conclude that the octathymidylate was bound to the (dA)8.(dT)8 sequence in a parallel orientation with respect to the (dA)8 containing strand. This result reflects the ability of thymine to form two hydrogen bonds with an adenine already engaged in a Watson-Crick base pair. This study shows that it is possible to design DNA-binding oligodeoxynucleotides that could selectively recognize and cleave polypurine-polypyrimidine sequences in double-stranded DNA. PMID- 2925641 TI - Purification and protein sequence analysis of rat liver prolactin receptor. AB - Prolactin receptors were purified from rat liver membranes by single-step immunoaffinity chromatography using a specific monoclonal antibody to the rat liver prolactin receptor. Scatchard analysis of 125I-human growth hormone binding to the purified receptor revealed two classes of specific binding sites with Ka = 18.5 x 10(9) and 1.2 x 10(9) M-1. Considering that both classes of binding sites are responsible for high affinity prolactin binding, the partially purified receptor preparation had a binding activity of 1.69 nmol/mg protein, representing 1000-fold purification over microsomal receptors with a recovery of 52%. From three separate purifications, 6 mg of partially purified prolactin receptor were obtained with a purity of approximately 4 to 6.5%. Thus, the use of monoclonal antibody for affinity chromatography resulted in a large improvement of prolactin receptor purification compared to previous hormone affinity chromatography (300 fold purification, 15% recovery). The purified receptor was run on preparative sodium dodecyl sulfate polyacrylamide gel electrophoresis, and a homogeneous preparation of prolactin receptor was obtained by electroelution from gel slices corresponding to Mr 38,000-43,000. Immunoblot analysis using a radiolabeled monoclonal antibody revealed two separate but closely located bands of Mr 42,000 and 40,000 in microsomal, partially purified, and electroeluted preparations. The homogeneous receptor protein was extensively digested with L-1-tosylamido-2 phenylethyl chloromethyl ketone trypsin, and 10 internal amino acid sequences of the rat liver prolactin receptor were determined by gas-phase sequence analysis. Oligonucleotide probes were prepared against two of these internal sequences, and a prolactin receptor cDNA was isolated from a rat liver library using one of these probes (Boutin, J. M., Jolicoeur, C., Okamura, H., Gagnon, J., Edery, M., Shirota, M., Banville, D., Dusanter-Fourt, I., Djiane, J., and Kelly, P. A. (1988) Cell 53, 69-77). The amino acid sequence deduced from the cDNA reveals three potential sites of N-linked glycosylation, two of which were confirmed during protein sequencing. The prolactin receptor was characterized by affinity labeling with 125I-human growth hormone. Cross-linking of microsomes revealed a single band for the hormone-receptor complex with Mr 62,000. On the other hand, cross-linking of Triton X-100-solubilized or partially purified receptor with labeled hormone resulted in the appearance of two bands with Mr 62,000 and 102,000, suggesting the existence of a subunit structure of the prolactin receptor, or alternatively, the existence of two types of prolactin receptor.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2925642 TI - Beta gamma-subunit of bovine transducin composed of two components with distinctive gamma-subunits. AB - During the process of transduction of a photon signal in vertebrate rod outer segments, transducin, a guanine nucleotide binding protein, mediates between a photobleaching intermediate of rhodopsin and a cGMP-phosphodiesterase. We report here that the beta gamma-subunit of bovine transducin (T beta gamma) characterized so far consists of two components (T beta gamma-1 and T beta gamma 2), which can be separated by anion exchange chromatography under nondenaturing conditions. Both components consisted of two polypeptides of Mr 36,000 (T beta) and about 8,000 (T gamma) in sodium dodecyl sulfate polyacrylamide (13%) gel electrophoresis. On a further analysis by 8 M urea/sodium dodecyl sulfate polyacrylamide gel electrophoresis, T gamma subunits of T beta gamma-1 and T beta gamma-2 showed Mr values of 8,000 (T gamma-1) and 6,000 (T gamma-2), respectively. Amino acid compositions of both T gamma-1 and T gamma-2 roughly corresponded with that of T gamma previously reported and were quite different from that of gamma-subunit of cGMP-phosphodiesterase. Western blot analysis of freshly isolated rod outer segments by an antiserum raised against a mixture of T beta gamma-1 and T beta gamma-2 revealed the presence of both components in the membranes of a starting material. This observation excludes the possibility that one of the components might be produced artificially in the course of the purification. In the presence of a photobleaching intermediate of either unphosphorylated or phosphorylated rhodopsin, the binding of guanosine 5'-(beta, gamma-imido)triphosphate (GppNHp) to the alpha-subunit of transducin (T alpha) was remarkably enhanced with increasing concentrations of purified T beta gamma 2. On the contrary, T beta gamma-1 retained little ability, if any, to enhance the GppNHp binding to T alpha; the ability of T beta gamma-1 was at least 30 times lower than that of T beta gamma-2. Such a low activity of T beta gamma-1 was attributed to inability for coupling of T alpha with a photobleaching intermediate of rhodopsin. These results indicate that T gamma-2 is essential for the GTP binding of transducin. The role of T gamma-1 in vertebrate photoreceptor cells was discussed. PMID- 2925643 TI - Rhesus monkey apolipoprotein(a). Sequence, evolution, and sites of synthesis. AB - Human lipoprotein(a) is a low density lipoprotein-like lipoprotein whose concentration in plasma is correlated with atherosclerosis. The characteristic protein component of lipoprotein(a) is apolipoprotein(a) (apo(a)) which is disulfide-linked to apolipoprotein B-100. Sequencing of rhesus monkey apo(a) cDNA suggests that this protein, like human apo(a), is highly similar to plasminogen. Sequence data suggests that a plasminogen-like protease activity and kringle 1-, 2-, 3-, and 5-like domains are unnecessary for apo(a) function, but a highly repeated kringle four-like domain is important. Liver is the major site of apo(a) RNA synthesis; reduced amounts of message were also found in testes and brain. Co expression with apoB-100 and plasminogen in rhesus tissues is not mandatory. PMID- 2925644 TI - Lipid transport during mitosis. Alternative pathways for delivery of newly synthesized lipids to the cell surface. AB - A number of cellular processes involving vesicle transport are inhibited during mitosis. In the present study we asked whether the transport of a newly synthesized glycerophospholipid and (some) sphingolipids from their site(s) of intracellular synthesis to the plasma membranes of Chinese hamster ovary cells was also inhibited at mitosis. (i) For phospholipids, we examined the movement of phosphatidylethanolamine (PE) following its de novo synthesis from [3H]ethanolamine (Sleight, R. G., and Pagano, R. E. (1983) J. Biol. Chem. 258, 9050-9058). Plasma membrane PE was distinguished from intracellular PE by its derivatization with the amino-reactive reagent, trinitrobenzenesulfonic acid, under nonpermeating conditions. Both the steady state amount of PE and the rate of appearance of newly synthesized PE at the cell surface were quantified. Transport of newly synthesized PE to the plasma membrane was not inhibited at mitosis but was found to be a rapid process similar to that previously reported for interphase cells. (ii) For sphingolipids, we examined the transport of fluorescent analogs of sphingomyelin and glucosylceramide (GlcCer) to the plasma membrane following their de novo synthesis from the fluorescent sphingolipid precursor, N-[7-(4-nitrobenzo-2-oxa-1,3-diazole)]aminocaproyl D-erythro sphingosine (Lipsky, N. G., and Pagano, R. E. (1985a) J. Cell Biol. 100, 27-34). Transport of fluorescent sphingomyelin and glucosylceramide to the plasma membrane was inhibited in mitotic cells but not in interphase or G1 cells. These results are discussed in terms of alternative mechanisms for delivery of the newly synthesized lipids to the outer leaflet of the plasma membrane bilayer. PMID- 2925645 TI - A sulfated glucosylceramide from rat kidney. AB - A novel sulfated glycosphingolipid containing a sulfated glucosyl residue was isolated from rat kidney and purified to homogeneity by column chromatographies with DEAE-Sephadex and silica beads. By compositional analyses, permethylation studies, one- and two-dimensional proton magnetic resonance spectroscopy, infrared spectroscopy, negative secondary ion mass spectrometry, solvolysis, and immunostaining on thin layer chromatogram, the structure of this glycolipid was proposed to be HSO3-3Glc beta 1-1Cer (where Cer is ceramide). The ceramide portion consisted of 4-D-hydroxysphinganine as the sole long chain base, and the fatty acid consisted of predominantly tetracosanoic acid, deduced from both composition analysis and negative secondary ion mass spectrometry. The yield of glucosyl sulfatide was about 5 nmol/g of tissue, being about three times as much as that of lactosylceramide sulfate. PMID- 2925646 TI - Plant cells contain calsequestrin. AB - Calsequestrin is a high capacity low affinity Ca2+-binding protein thought to be essential for the function of the intracellular rapid releasable Ca2+ pool of a variety of animal cells. Here we show that two types of plant tissues, cultured Streptanthus tortuosus cells and spinach leaves, contain a form of calsequestrin. In subcellular fractions of S. tortuosus cells, Stains-all staining reveals a metachromatically blue-staining 56,000-Da protein enriched in the microsomal fraction. This protein shares several biochemical characteristics with animal calsequestrin: 1) it changes its apparent molecular weight with the pH; 2) it is able to bind 45Ca2+ on nitrocellulose transfers; and 3) it is recognized by antibodies against canine cardiac calsequestrin. Calsequestrin was also identified in spinach leaves using a direct extraction procedure that was developed for muscle calsequestrin. Thus, our results demonstrate that plant cells contain calsequestrin within a subcellular membrane fraction. These results also suggest that calsequestrin is an ubiquitous protein rather than being limited only to animal cells. PMID- 2925647 TI - Release of endothelial cell lipoprotein lipase by plasma lipoproteins and free fatty acids. AB - Lipoprotein lipase (LPL) bound to the lumenal surface of vascular endothelial cells is responsible for the hydrolysis of triglycerides in plasma lipoproteins. Studies were performed to investigate whether human plasma lipoproteins and/or free fatty acids would release LPL which was bound to endothelial cells. Purified bovine milk LPL was incubated with cultured porcine aortic endothelial cells resulting in the association of enzyme activity with the cells. When the cells were then incubated with media containing chylomicrons or very low density lipoproteins (VLDL), a concentration-dependent decrease in the cell-associated LPL enzymatic activity was observed. In contrast, incubation with media containing low density lipoproteins or high density lipoproteins produced a much smaller decrease in the cell-associated enzymatic activity. The addition of increasing molar ratios of oleic acid:bovine serum albumin to the media also reduced enzyme activity associated with the endothelial cells. To determine whether the decrease in LPL activity was due to release of the enzyme from the cells or inactivation of the enzyme, studies were performed utilizing radioiodinated bovine LPL. Radiolabeled LPL protein was released from endothelial cells by chylomicrons, VLDL, and by free fatty acids (i.e. oleic acid bound to bovine serum albumin). The release of radiolabeled LPL by VLDL correlated with the generation of free fatty acids from the hydrolysis of VLDL triglyceride by LPL bound to the cells. Inhibition of LPL enzymatic activity by use of a specific monoclonal antibody, reduced the extent of release of 125I-LPL from the endothelial cells by the added VLDL. These results demonstrated that LPL enzymatic activity and protein were removed from endothelial cells by triglyceride-rich lipoproteins (chylomicrons and VLDL) and oleic acid. We postulate that similar mechanisms may be important in the regulation of LPL activity at the vascular endothelium. PMID- 2925648 TI - Characterization of volume-sensitive, calcium-permeating pathways in the osteosarcoma cell line UMR-106-01. AB - Measurements of cell volume changes, free cytosolic Ca2+ concentration [( Ca2+]i) with Fura 2 and cell membrane potential with 3,3'-dipropylthiodicarbocyanine iodide were used to study the effect of cell volume change on Ca2+ influx and the membrane potential of the osteoblastic osteosarcoma cell line, UMR-106-01. Swelling the cells by hypo-osmotic stress was followed by reduction in cell volume which was markedly impaired by removal of medium Ca2+. Accordingly, cell swelling resulted in [Ca2+]i increase only in the presence of medium Ca2+. The cell swelling-activated Ca2+ entry pathway was active at resting membrane potentials, and Ca2+ influx through this pathway markedly increased upon cell hyperpolarization. A linear relationship between Ca2+ entry and the potential across the plasma membrane was observed. Thus, the volume-activated Ca2+ permeating pathway in UMR-106-01 cells has conductive properties. These pathways do not spontaneously inactivate with time when the cells are not allowed to volume regulate. The pathway can be blocked by micromolar concentrations of nicardipine and La3+ but display very low sensitivity to diltiazem and verapamil. Activation of the volume-sensitive, Ca2+ permeating pathway was not dependent on an increase in [Ca2+]i. Likewise, activation of the pathway was independent of a change in membrane potential between -85 and -3 mV. The increase in [Ca2+]i resulted in hyperpolarization of the cells, probably due to activation of Ca2+ activated K+ channels. The volume-sensitive pathways were partially active under isotonic conditions. Their activity was inhibited by cell shrinkage and increased by cell swelling. The pathways were sensitive to small changes in cell volume, particularly around a medium osmolarity of 310 mosM. PMID- 2925649 TI - Purification and properties of phloroglucinol reductase from Eubacterium oxidoreducens G-41. AB - Phloroglucinol reductase was purified 90-fold to homogeneity from the anaerobic rumen organism Eubacterium oxidoreducens strain G-41. The enzyme is stable in the presence of air and is found in the soluble fraction after ultracentrifugation of cell extract. Ion-exchange, hydrophobic interaction, and affinity chromatography were used to purify the enzyme. The native Mr is 78,000, and the subunit Mr is 33,000 indicating an alpha 2 homodimer. The enzyme is specific for phloroglucinol and NADPH. The Km and Vmax are 600 microM and 640 mumol min-1 mg-1 (pH 7.2) for phloroglucinol, and 6.7 microM and 550 mumol min-1 mg-1 (pH 6.8) for NADPH; the Km and Vmax for the reverse direction are 290 microM and 140 mumol min-1 mg-1 (pH 7.2) for dihydrophloroglucinol, and 27 microM and 220 mumol min-1 mg-1 (pH 7.2) for NADP. Temperature and pH optima are 40 degrees C and 7.8 in the forward direction. The pure enzyme is colorless in solution and flavins are absent. Analysis for cobalt, manganese, molybdenum, vanadium, tungsten, selenium, copper, nickel, iron, and zinc indicated that these metals are not components of the phloroglucinol reductase. Cupric chloride, n-ethylmaleimide, and p chloromercuribenzoate are potent inhibitors of enzyme activity. The properties of phloroglucinol reductase indicate that it functions in the pathway of anaerobic degradation of trihydroxybenzenes by catalyzing reduction of the aromatic nucleus prior to ring fission. PMID- 2925650 TI - Membrane topology of mammalian cytochromes P-450 from liver endoplasmic reticulum. Determination by trypsinolysis of phenobarbital-treated microsomes. AB - We have studied the membrane topology of liver microsomal cytochromes P-450 derived from phenobarbital-treated rabbits via trypsinolysis of intact microsomes, recovery of solubilized peptide fragments by ultracentrifugation and liquid chromatography, primary structure determination by Edman microsequence analysis, and database searching to match isolated fragments with parent sequences. Relative to the primary structure of isozyme 2, the major phenobarbital-inducible form, fragments were isolated beginning at residues Glu86, Ile101, Arg126, Cys152, Leu198, Ser211, Asn237, Glu327, Asn385, Thr407, Phe408, Phe413, and Thr444. Such results show that this family of structurally related cytochromes is bound to the endoplasmic reticulum membrane by only one or two transmembrane segments, located at the NH2-terminal end of the polypeptide chain. The remainder of the protein, from residue approximately 50 to the COOH terminus must exist as a catalytic, heme-containing domain exposed on the cytosolic side of the membrane. Furthermore, our results indicate that the catalytic domain must be peripherally associated with the membrane surface. This would imply that substrates might have access to the active site of the cytochrome P-450 either by diffusion from the cytosol or from within the lipid bilayer. PMID- 2925651 TI - Lipid synthesis in permeabilized cultured rat hepatocytes. AB - Hepatic lipid synthesis was verified and studied in lysolecithin-permeabilized cultured rat hepatocytes and compared to that of intact liver cells. Triacylglycerol synthesis in permeabilized cells incubated in the presence of glycerol 3-phosphate and long chain fatty acids approached that of intact hepatocytes. Similarly, phosphatidylcholine synthesis in permeable cells incubated in the presence of exogenous CDP-choline was similar to that of intact hepatocytes and at the expense of microsomal neutral lipid synthesis. Phosphatidic acid accumulation in lysolecithin-permeabilized liver cells was remarkably increased as compared to that of intact cells, and its synthesis was mostly accounted for by the activity of mitochondrial glycerol-3-phosphate acyltransferase. Mitochondrial-generated phosphatidate was found to migrate to the endoplasmic reticulum, thus establishing a novel lipid esterification pathway which begins in mitochondrial glycerol 3-phosphate acylation and results in microsomal triacylglycerol and phospholipid synthesis. The free access of permeabilized liver cells to substrates and modulators of lipid synthesis, while maintaining an overall synthetic pattern similar to that of intact hepatocytes, makes them a system of choice for studying hepatic lipid synthesis in general and the microsomal/mitochondrial distribution of fluxes in particular. PMID- 2925652 TI - Platelet-derived growth factor production by human umbilical vein endothelial cells is regulated by basic fibroblast growth factor. AB - Human umbilical vein endothelial cells express the B chain gene (c-sis) of platelet-derived growth factor (PDGF). PDGF acts as a mitogen for mesenchymal cells and has recently been reported to be a potent vasoconstrictor (Berk, B. C., Alexander, R. W., Brock, T. A., Gimbrone, M. A., Jr., and Webb, R. C. (1986) Science 232, 87-90). Regulation of c-sis therefore, may play an important role in maintaining and controlling the integrity of the vasculature. We report here that basic fibroblast growth factor (bFGF), a growth factor for endothelial cells in culture, significantly decreases the amount of PDGF-like protein secreted by these cells. Levels of c-sis mRNA increase more than 10-fold in the absence of bFGF. This effect is specific for the B chain of PDGF as transcript levels of other growth factors synthesized by endothelial cells, such as transforming growth factor beta are not affected by bFGF. c-sis mRNA levels increase 12 h after bFGF removal as the cells begin to accumulate in G0 stage of the cell cycle and remain elevated for at least 96 h. Transcript levels fall again upon re exposure of the cells to bFGF. bFGF may regulate c-sis mRNA levels and PDGF protein production by endothelial cells either directly, or indirectly via cell cycle arrest at G0. This effect is not due to nonspecific cessation of cell growth because arresting the cells at S phase or in metaphase does not result in increased c-sis transcript levels. PMID- 2925654 TI - Primary structure and gene localization of human prolidase. AB - Complementary DNA clones of prolidase (imidodipeptidase, EC 3.4.13.9) were isolated from human liver and placental cDNA libraries. Two clones named lambda PL21 and lambda PP6 from the liver and placental cDNA libraries, respectively, were analyzed in detail. The first clone, lambda PL21, carried a cDNA insert of 1.7 kilobase pairs and covered all the coding region of human prolidase mRNA. The second clone, lambda PP6, contained a 1.8-kilobase insert with a full-length 3' untranslated region. Comparison of the amino acid sequence predicted from the nucleotide sequence of the cDNA insert of the two clones with the partial amino acid sequence determined by Edman degradation of peptides derived from human erythrocyte prolidase established that both clones code for human prolidase. The amino terminus of the human mature enzyme is blocked and seems to begin with the sequence X-Ala-Ala-Ala. Presumably no processing occurs at the carboxyl terminus. The mature enzyme is composed of 492 residues, corresponding to Mr 54,305. The sequence of prolidase is unique and not similar to any known protein, except for a significant similarity to regions of F1-ATPase alpha and beta subunits from various sources. The gene has been mapped to the short arm of chromosome 19 (19p13.2). Elucidation of the complete amino acid sequence and the gene location of prolidase should provide the basis for understanding structure-function relationships and also inherited disorders caused by deficiency of this metabolically important enzyme. PMID- 2925653 TI - Thyroid hormone and circadian regulation of the binding activity of a liver specific protein associated with the 5'-flanking region of the S14 gene. AB - Recent studies have described a DNase I hypersensitive site in the 5'-flanking region of the rat hepatic S14 gene that is closely associated with its expression. A 111-base pair subfragment (-389 to -279) of this region interacts specifically in a gel shift assay with a protein present in hepatic nuclear protein extracts. This protein, designated P1, was not present in extracts of other tissues, even those in which the gene is expressed and hormonally regulated. The binding activity of P1 is exceedingly low in extracts from hypothyroid rats and is markedly increased by administration of thyroid hormone. However, the slow accumulation of P1 after thyroid hormone administration indicates that increased levels of P1 are not necessary for the acute hormonal induction of S14 gene expression. The level of P1 binding activity increases in the evening, synchronous with circadian variation of hepatic mRNA S14. Since neither P1 binding activity nor circadian variation in mRNA-S14 levels are observed in the other tissues expressing the S14 gene, P1 may function to modulate the circadian rhythm observed in hepatic S14 gene expression. DNase I footprinting analysis revealed that P1 binds to a defined nucleotide sequence, 5' AAAAGAGCTATTGATTGCCTGCA-3', located between -310 and -288 in the S14 gene. PMID- 2925656 TI - Evidence for two mechanisms by which tumor necrosis factor kills cells. AB - Tumor necrosis factor (TNF) can inhibit the differentiation of preadipocytes to adipocytes and will revert differentiated adipocytes to the preadipocyte state. TNF is not toxic to either adipocytes or preadipocytes when used alone but is highly toxic to these cells when used in conjunction with cycloheximide, yielding virtually 100% killing within 4-6 h of treatment. A cell line (TA1 R-6) was isolated which is resistant to the combined toxic effects of TNF and cycloheximide. This cell line is stable and, unlike the parental cell line, does not morphologically differentiate to adipocytes or express adipocyte-specific mRNAs. It has a more transformed appearance and growth pattern and, while resistant to the toxic effects of TNF and cycloheximide in a 6-h assay, has become sensitive to cytotoxicity induced by TNF used alone in a 3-day assay. The adipocyte differentiation-inducing agents, dexamethasone and indomethacin, block the cytotoxicity induced by TNF alone in the TA1 R-6 line but do not block the rapid cytotoxicity of TNF and cycloheximide in the parental line. These results provide both genetic and pharmacologic evidence that there are at least two distinct or overlapping pathways by which TNF mediates its effects. PMID- 2925655 TI - Inhibitors of sterol synthesis. Characterization of side chain oxygenated derivatives formed upon incubation of 3 beta-hydroxy-5 alpha-cholest-8(14)-en-15 one with rat liver mitochondria. AB - 3 beta-Hydroxy-5 alpha-cholest-8(14)-en-15-one, a potent inhibitor of sterol biosynthesis, was incubated with rat liver mitochondrial preparations in the presence of NADPH. The following four major products were isolated and characterized by nuclear magnetic resonance and mass spectrometry: (25R)- and (25S)-3 beta,26-dihydroxy-5 alpha-cholest-8(14)-en-15-one (4:1 ratio), 3 beta hydroxy-15-oxo-5 alpha-cholest-8(14)-en-26-oic acid, and 3 beta,25-dihydroxy-5 alpha-cholest-8(14)-en-15-one. In addition, 3 alpha,26-dihydroxy-5 alpha-cholest 8(14)-en-15-one and 3 beta,24-dihydroxy-5 alpha-cholest-8(14)-en-15-one were identified as minor products by capillary gas chromatography-mass spectrometry. PMID- 2925657 TI - Complex formation with the fibroin gene enhancer through a protein-protein interaction analyzed by a modified DNA-binding assay. AB - The distal upstream region of the fibroin gene, -238 to -73, is known to contain the cis-acting element(s) responsible for tissue-specific transcription enhancement in vitro. To identify factor(s) trans-acting on this region, we have developed a modified nitrocellulose blot protein-DNA binding procedure that detects DNA-protein complexes via protein-protein interaction. A protein that does not bind to DNA as a monomer cannot be detected by standard Southwestern blotting. To detect protein-DNA complexes involving both protein-DNA and protein protein interactions, the protein blot was reacted with the extract protein to form a protein complex on the filter, in the presence of the DNA probe. This new method revealed that the 75-kDa protein binds to the enhancer region of the fibroin gene in the presence of the second protein(s). The 75-kDa protein and the factor(s) mediating DNA binding activity were recovered in two different column fractions. The level of the 75-kDa protein appeared to be much higher in silk gland extracts than in nonsilk gland extracts, whereas the mediating factor(s) distributed evenly. These observations suggest that the distal upstream region of the fibroin gene can be specifically recognized by a protein complex composed of at least two distinct proteins, through protein-protein interaction. PMID- 2925658 TI - Properties of lipid complexes with amphipathic helix-forming peptides. Role of distribution of peptide charges. AB - The peptides [Glu1,8,Leu11,17] 18A and [Glu4,9,Leu11,17] reverse-18A are 18 residue peptides designed to form amphipathic helices with opposite charge distribution; [Glu1,8,Leu11,17] 18A having positively charged residues at the hydrophobic/hydrophilic interface. Both [Glu1,8,Leu11,17] 18A and [Glu4,9,Leu11,17] reverse-18A strongly disrupt the bilayer structure as indicated by the relatively narrow lipid 1H and 31P NMR peaks. In addition, the 1H chemical shift of the quaternary ammonium methyl groups indicates that [Glu1,8,Leu11,17] 18A forms smaller lipoprotein particles with dimyristoylphosphatidylcholine (DMPC) than does [Glu4,9,Leu11,17] reverse-18A. However, motional properties of the lipid head group indicate that no specific salt bridges are formed between the phospholipid head group and the side chains of polar amino acids of either of the two peptides. In addition, the acyl chain conformation for the DMPC complexes with [Glu1,8,Leu11,17] 18A and with [Glu4,9,Leu11,17] reverse-18A are indistinguishable by the criterion of IR spectroscopy. The 2H linewidth of the solvent 2H2O remains narrower in frozen solutions of the DMPC-[Glu1,8,Leu11,17] 18A complexes suggesting the presence of more unfrozen bound water in this case. The two peptides exhibit many similarities in their interaction with lipids. However, [Glu1,8,Leu11,17] 18A can more readily lyse vesicles and activate lecithin:cholesterol acyltransferase. These differences do not appear to result from differences in specific charge interactions between the lipid and peptide but may be manifested through differences in hydration properties. PMID- 2925659 TI - Purification, characterization, and amino-terminal sequence of rat ovarian receptor for luteinizing hormone/human choriogonadotropin. AB - The luteinizing hormone (LH)/human choriogonadotropin (hCG) receptor of rat ovary was solubilized with Lubrol PX in the presence of 20% glycerol and protease inhibitors, and purified by one-step affinity chromatography. Purified receptor had a specific hCG binding capacity of 4900 pmol/mg protein, and displayed a single class of high affinity binding sites (Ka = 6.20 X 10(9) M-1). An 11,200 fold purification over the starting crude homogenate was achieved. The purified LH/hCG receptor was identified by sodium dodecyl sulfate-gel electrophoresis and silver staining as a single protein of 92 kDa. The ability of the purified 92-kDa protein to specifically bind hormone was demonstrated by electroblotting onto Immobilon P membrane, incubation with 125I-labeled hCG, and autoradiography of the blot. In addition to a 92-kDa band, ligand blotting also yielded a 170-kDa band representing receptor dimer. Covalent cross-linking of hCG, with isotope in either the alpha- or beta-subunit, to membrane-bound receptor produced complexes that contained a single receptor component of approximately 92 kDa. The cross linking studies indicated that both subunits interact with receptor and also suggested receptor dimer formation. Following sodium dodecyl sulfate electrophoresis, purified receptor was electroblotted onto polyethylenimine treated glass fiber filters for direct microsequencing in a gas-phase sequenator. Eleven cycles of sequence analysis yielded the unique sequence: NH2-Arg-Glu-Leu Ser-Gly-Ser-Leu-XXX-Pro-Glu-Pro-COOH. These results indicate that the rat ovarian LH/hCG receptor is a protein of 92 kDa which can be easily purified in microgram amounts. This study also describes a relatively simple technique for electroblotting and microsequencing that should be applicable to other membrane bound hormone receptors. PMID- 2925660 TI - Bowringia milbraedii agglutinin. Specificity of binding to early processing intermediates of asparagine-linked oligosaccharide and use as a marker of endoplasmic reticulum glycoproteins. AB - We have purified a protein with hemagglutinating activity from the seeds of a West African legume, Bowringia milbraedii. The purified protein, designated BMA, has a native Mr = 38,000 on gel filtration and a subunit size of Mr = 16,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing or nonreducing conditions. Hemagglutination was inhibited most effectively by Man alpha 1----2 linked sugars. Affinity chromatography of oligosaccharides on BMA Sepharose showed that Man alpha 1----2Man alpha 1----2Man alpha 1----3Man beta 1- --4GlcNAcol (where GlcNAcol is N-acetylglucosaminitol) and Man alpha 1----2Man alpha 1----3Man beta 1----4GlcNAcol were retarded on the column, whereas Man alpha 1----3Man beta 1----4GlcNAcol did not bind. Oligomannosidic-type glycans obtained by treatment of [3H] mannose-labeled baby hamster kidney cells with endo beta-N-acetylglucosaminidase H bound more strongly to BMA-Sepharose and required 10 or 200 mM methyl-alpha-mannoside for elution. Oligosaccharides bearing the sequence Man alpha 1----2Man alpha 1----6Man alpha 1----6Man, i.e. Man9GlcNAc and certain isomers of Man8GlcNAc and Man7GlcNAc, bound more tightly than other Man8 GlcNAc and Man7GlcNAc isomers lacking this sequence. Man6GlcNAc and Man5GlcNAc were weakly bound. These results suggest that BMA binds preferentially to glycoproteins that are subjected to early steps of oligosaccharide processing in the endoplasmic reticulum but not to glycoproteins that are exposed to more extensive processing by Golgi mannosidases. Staining of permeabilized cells with BMA-chromophore conjugates revealed a reticular cytoplasmic pattern consistent with a preferential visualization of the endoplasmic reticulum. BMA staining was less evident in the juxtanuclear regions that were stained brightly with wheat germ agglutinin, a lectin that binds preferentially to sialylated glycoproteins located in Golgi compartments. PMID- 2925661 TI - Identification of a lysosome membrane protein which could mediate ATP-dependent stable association of lysosomes to microtubules. AB - We have previously reported that purified thyroid lysosomes bind to reconstituted microtubules to form stable complexes (Mithieux, G., Audebet, C., and Rousset, B. (1988) Biochim. Biophys. Acta 969, 121-130), a process which is inhibited by ATP (Mithieux, G., and Rousset, B. (1988) Biochim. Biophys. Acta 971, 29-37). Among detergent-solubilized lysosomal membrane protein, we identified a 50-kDa molecular component which binds to preassembled microtubules. The binding of this polypeptide to microtubules was decreased in the presence of ATP. We purified this 50-kDa protein by affinity chromatography on immobilized ATP. The 50-kDa protein bound to the ATP column was eluted by 1 mM ATP. The purified protein, labeled with 125I, exhibited the ability of interacting with microtubules. The binding process was inhibited by increasing concentrations of ATP, the half maximal inhibitory effect being obtained at an ATP concentration of 0.35 mM. The interaction of the 50-kDa protein with microtubules is a saturable phenomenon since the binding of the 125I-labeled 50-kDa protein was inhibited by unlabeled solubilized lysosomal membrane protein containing the 50-kDa polypeptide but not by the same protein fraction from which the 50-kDa polypeptide had been removed by the ATP affinity chromatography procedure. The 50-kDa protein has the property to bind to pure tubulin coupled to an insoluble matrix. The 50-kDa protein was eluted from the tubulin affinity column by ATP. These findings support the conclusion that a protein inserted into the lysosomal membrane is able to bind directly to microtubules in a process which can be regulated by ATP. We propose that this protein could account for the association of lysosomes to microtubules demonstrated both in vitro and in intact cells. PMID- 2925663 TI - Human aldehyde dehydrogenase. Purification and characterization of a third isozyme with low Km for gamma-aminobutyraldehyde. AB - An enzyme which catalyzes dehydrogenation of gamma-aminobutyraldehyde has been purified to homogeneity from human liver and identified as an isozyme of aldehyde dehydrogenase (EC 1.2.1.3); two other isozymes, previously obtained in a homogeneous form, are known as E1 and E2. Affinity chromatography on NAD-agarose (N6 with 8 carbon spacer) yields homogeneous enzyme which migrates as two components on isoelectric focusing with pI = 5.3 and 5.45. These two components, separated by fast protein liquid chromatography on a Mono-P HR 5/20 column, have similar Km values for gamma-aminobutyraldehyde, acetaldehyde, propionaldehyde, and NAD. The Km value for gamma-aminobutyraldehyde is 8.0-14.0 microM versus 760 microM for E1 and 512 microM for E2. The enzyme's molecular weight, subunit molecular weight, and amino acid composition are similar to those of the E1 and E2 isozymes. The enzyme also interacts with anti-E1 and anti-E2 antibodies; it is relatively insensitive to disulfiram inhibition and is neither activated nor inhibited by magnesium. Its absorption spectrum, where the ratio of 280/260 nm is 1.1 and a weak absorption is seen in the 340 nm range (Racker band), suggests the presence of bound coenzyme. gamma-Aminobutyraldehyde dehydrogenase (with Km value of 15 microM for gamma-aminobutyraldehyde) was previously partially purified from Pseudomonas fluorescens (Jakoby, W.B., and Fredericks, J. (1959) J. Biol. Chem. 234, 2145-2150) but never from a mammalian organism. PMID- 2925662 TI - Rapid induction of rat liver S14 gene transcription by thyroid hormone. AB - The mRNA coding for the rat liver S14 protein (Mr 17,000; pI 4.9) is rapidly induced by triiodothyronine (T3) (Jump, D. B., Narayan, P., Towle, H. C., and Oppenheimer, J. H. (1984) J. Biol. Chem. 259, 2789-2797). In an effort to define the molecular basis for the rapid increase in mRNAS14, the in vitro run-on activity and chromatin structure of the S14 gene was examined. Following injection of hypothyroid rats with a receptor-saturating dose of T3, a 5-min lag period preceded a rapid increase in S14 gene transcription. S14 transcriptional activity was induced 3.8-fold within 15 min and reached nearly 70% of the maximal 9-fold induction within 60 min of T3 administration. Hepatic mRNAS14 levels were induced 2.4-, 19-, and 24-fold within 15 min, 4 h, and 24 h, respectively. Thus, the rapid T3-mediated induction of mRNAS14 was due, in large part, to a rapid and apparent direct effect of T3 on S14 transcriptional activity. Analysis of S14 chromatin structure showed that the Hss-3 DNase I hypersensitive site located 3.3 kilobases (kb) upstream from the hepatic S14 cap site was present in both euthyroid and hyperthyroid states, but either absent or present at diminished DNase I sensitivity in the hypothyroid state. However, within 5 min of T3 administration to hypothyroid rats, the Hss-3 DNase I hypersensitive site was significantly induced. The induction of this structure preceded T3 induction of S14 gene transcription. Other DNase I hypersensitive sites located adjacent to the S14 cap site at -65 to -265 base pairs (Hss-1) or upstream at -1.3 kb (Hss 2), -2.1 kb (Hss-3'), -5.3 kb (Hss-4), and -6.2 kb (Hss-5) remained unaffected by changes in S14 gene transcription. The rapid T3 effect on the Hss-3 DNase I hypersensitive site may reflect the presence of T3 receptors in the vicinity of this chromatin locus. Modification of chromatin structure in the vicinity of the Hss-3 site may be an important antecedent event for T3-mediated induction of S14 gene transcription. PMID- 2925664 TI - Crystallization and molecular symmetry of ornithine decarboxylase from Lactobacillus 30a. AB - Ornithine decarboxylase from Lactobacillus 30a is representative of the large subunit (80 kDa), oligomeric, pyridoxal phosphate-dependent amino-acid decarboxylases. Yellow crystals of ornithine decarboxylase are obtained from polyethylene glycol solutions and belong to space group P6 with unit cell constants a = b = 194.9 and c = 97.44 A, alpha = beta = 90 degrees and gamma = 120 degrees, V = 3.21 x 10(6) A3. Still photographs show reflections at better than 2.4-A resolution. Electron micrographs reported by Guirard and Snell (Guirard, B.M., and Snell, E.E. (1980) J. Biol. Chem. 255, 5960-5964) reveal that the ornithine decarboxylase dodecamer is a hexagonally shaped particle with a point-to-point distance of approximately 210 A and a thickness of approximately 70 A. The crystallographic unit cell can thus accommodate one 10(6)-Da dodecamer (Vm = 3.2 A3/Da), implying that a dimer occupies an asymmetric unit. Tanaka rotation function analysis, using native data (5-7 A) collected from three crystals, reveals that the particle has the expected 622 molecular symmetry with molecular 2-fold axes lying at 20 degrees and 50 degrees from a in the a-b plane. A search for suitable heavy atom derivatives is underway. PMID- 2925665 TI - Endothelial albumin binding proteins are membrane-associated components exposed on the cell surface. AB - The heterobifunctional, photoactivatable, thiol-cleavable cross-linker sulfosuccinimidyl 2-(p-azido-salicylamido)ethyl-1,3'-dithiopropionate (SASD) was radioiodinated and used to determine whether endothelial albumin binding proteins (ABP) recently identified (Ghinea, N., Fixman, A., Alexandru, D., Popov, D., Hasu, M., Ghitescu, L., Eskenasy, M., Simionescu, M., and Simionescu, N. (1988) J. Cell Biol. 107, 231-239) are plasma membrane-associated components exposed on the cell surface. Microvascular endothelial cells (MEC) freshly isolated from rat epididymal fat were incubated with 125I-2-(p-azidosalicylamido)ethyl-1,3' dithiopropionate (ASD)-albumin conjugate which upon photolysis by UV light was cross-linked to the receptor proteins. By cleaving the disulfide linkages of the cross-linker with 5% beta-mercaptoethanol and the ligand-receptor interactions with 0.1% sodium dodecyl sulfate, the radioiodinated ASD moiety remained attached to the receptor peptides which were further detected by 5% sodium dodecyl sulfate polyacrylamide gel electrophoresis followed by autoradiography. In parallel, samples were examined by ligand blotting with albumin-gold complex. The results showed that in these experimental conditions ABP are represented by two major peptides of 31 and 18 kDa and two minor bands of 73 and 56 kDa. Densitometric scanning showed that the two major bands constitute more than 70% of the total ABP. The four peptides were not apparent if the samples were not UV-irradiated. The binding of the radioiodinated ligand to ABPs was reduced by approximately 82% in the presence of excess competitive unlabeled albumin. When MEC were incubated with unlabeled SASD and exposed to UV light, the autoradiographic banding pattern obtained was similar to that of either radioiodinated receptor proteins or MEC not treated with SASD. This indicated that the four albumin binding peptides are distinct proteins of the endothelial cell plasmalemma. PMID- 2925666 TI - Carrier-mediated transport of monoiodotyrosine out of thyroid cell lysosomes. AB - Monoiodotyrosine (MIT) crosses the lysosomal membrane of rat FRTL-5 thyroid cells by a carrier-mediated process. In egress studies, MIT lost from inside lysosomes was quantitatively recovered outside lysosomes as MIT, indicating that the compound was transported intact across the lysosomal membrane. In uptake studies, [125I]MIT entry required intact lysosomes and exhibited saturation kinetics. The apparent Km for MIT was approximately 1.5 microM and the Vmax was approximately 0.24 pmol/unit hexosaminidase/min. Countertransport of MIT was demonstrated, with an initial velocity of [125I]MIT uptake which reached a maximum at high intralysosomal MIT loading. Nonradioactive MIT and diiodotyrosine competed to approximately equivalent extents with [125I]MIT for uptake in countertransport experiments. The existence of a lysosomal MIT carrier in thyroid cells may explain how this product of thyroglobulin catabolism is transported to the cytosol for iodine salvage and reutilization. PMID- 2925667 TI - Stimulation in vitro of rabbit erythrocyte cytosol phospholipid-dependent protein kinase activity. A novel action of thyroid hormone. AB - L-Thyroxine (T4) and 3,3',5-L-triiodothyronine (T3) at 10(-10) M stimulated phospholipid- and Ca2+-dependent protein kinase activity in rabbit red cell cytosol in vitro by 151 and 176%, respectively. Kinase of 30-fold greater specific activity, developed with 0.4 mM NaCl from cytosol applied to DEAE cellulose, was also stimulated up to 2-fold by thyroid hormone. Hormone enhancement of kinase activity occurred after 60 min of incubation at 37 degrees C prior to enzyme assay. Thyroid hormone analogues triiodothyroacetic acid, 3,5 dimethyl-3'-isopropyl-L-thyronine, D-T3, D-T4, and 3,3',5'-L-triiodothyronine (reverse T3) were inactive. These results support a role for thyroid hormone endogenously in regulation of phospholipid-dependent protein kinase activity. PMID- 2925668 TI - Purification and characterization of the sea urchin embryo hatching enzyme. AB - The sea urchin hatching enzyme provides an interesting model for the control of gene expression during early development. In order to study its properties and developmental regulation, the hatching enzyme of the species Paracentrotus lividus has been purified. The fertilization envelopes of the embryos were digested before hatching by a crude culture supernatant previously made. The enzyme was then solubilized by 1 M NaCl and 0.5% 3-[(3 cholamidopropyl)dimethylammonio]-1-propanesulfonate and purified by hydrophobic chromatography on Procion-agarose. A 470-fold increase in specific activity was obtained. The kinetic parameters of the proteolytic activity using dimethylcasein as substrate are: Km = 120 micrograms x ml-1, Vm = 200 mumol x min-1 x mg-1, and kcat = 180 s-1 at 500 mM NaCl, 10 mM CaCl2, pH 8.0, at 35 degrees C. The purified enzyme is highly active on fertilization envelopes: at 20 degrees C and 500 mM NaCl, 10 mM CaCl2, pH 8.0, 100 ng of enzyme completely denudes embryos in about 20 min under standard conditions. The molecular mass of the enzyme was estimated as 57 kDa by gel filtration, 51 kDa by gel electrophoresis, and 52 kDa by amino acid analysis. The hatching enzyme was shown to be a glycoprotein which autolyzes to a 30-kDa inactive form. Antibodies raised against the 51- or 30-kDa forms reacted with both these forms. Immunoblotting experiments showed that the hatching supernatants contain important amounts of the autolyzed species. PMID- 2925669 TI - Solubilization and reconstitution characteristics of hepatic system A-mediated amino acid transport. AB - In the liver, System A-mediated uptake of neutral amino acids may play a key role in metabolic control. Knowing the properties of the solubilized and reconstituted System A activity is important for future studies on the purification of the carrier protein. Solubilization of System A activity by the combination of 2.5% cholate and 4 M urea resulted in greater than 85% extraction of the activity. Previous removal of easily extracted plasma membrane proteins with 1% cholate alone followed by solubilization of the transporter with cholate/urea resulted in a 2-fold enrichment in transport activity. Based on the observation that the carrier protein aggregates in the presence of low detergent concentrations, a selective polyethylene glycol precipitation procedure was developed resulting in recovery of more than 70% of the initial transport activity and less than 10% of the total protein. A concomitant 10-fold enrichment in carrier activity was achieved. The precipitated carrier could be resuspended in buffer containing Triton X-100, asolectin, and glycerol. Transporter activity in this buffer was stable for up to 5 days when maintained at -20 degrees C or for 2 days at 4 degrees C. The general applicability of the devised reconstitution is illustrated by the presence of Systems N and Gly in the reconstituted proteoliposomes at specific activities greater than those in the native vesicles. PMID- 2925670 TI - Detection and characterization of a nucleoside transport system in human fibroblast lysosomes. AB - Lysosomes contain enzymatic activities capable of degrading nucleic acids to their constituent nucleosides, but the manner by which these degradation products are released from the lysosome is unknown. To investigate this process, human fibroblast lysosomes, purified on Percoll density gradients, were incubated with [3H]adenosine at pH 7.0, and the amount of adenosine taken up by the lysosomes was measured. Adenosine uptake by fibroblast lysosomes attained a steady state by 12 min at 37 degrees C and was unaffected by the presence of 2 mM MgATP or changes in pH from 5.0 to 8.0. An Arrhenius plot was linear with an activation energy of 12.9 kcal/mol and a Q10 of 2.0. Lysosomal adenosine uptake is saturable, displaying a Km of 9 mM at pH 7.0 and 37 degrees C. Various nucleosides and the nucleobase, 6-dimethylaminopurine, strongly inhibit lysosomal adenosine uptake, whereas neither D-ribose or nucleotide monophosphates have any significant effect upon lysosomal adenosine uptake. On a molar basis, purines are recognized more strongly than pyrimidines. Changing the nature of the nucleoside sugar from ribose to arabinose or deoxyribose has little effect on reactivity with this transport system. The known plasma membrane nucleoside transport inhibitors, dipyridamole and nitrobenzylthioinosine, inhibit lysosomal nucleoside transport at relatively low concentrations (25 microM) relative to the Km of 9 mM for lysosomal adenosine uptake. The half-times of [3H]inosine and [3H]uridine efflux from fibroblast lysosomes ranged from 6 to 8 min at 37 degrees C. Trans effects were not observed to be associated with either inosine or uridine exodus. In contrast to adenosine uptake, adenine primarily enters fibroblast lysosomes by a route not saturable by high concentrations of various nucleosides. In conclusion, the saturability of lysosomal adenosine uptake and its specific, competitive inhibition by other nucleosides indicate the existence of a carrier mediated transport system for nucleosides within fibroblast lysosomal membranes. PMID- 2925671 TI - Purification and characterization of NADPH-dependent cytosolic 3,5,3'-triiodo-L thyronine binding protein in rat kidney. AB - The NADPH-dependent cytosolic 3,5,3'-triiodo-L-thyronine(T3)-binding protein (CTBP) has been purified over 30,000-fold from rat kidney by using charcoal extraction, Mono Q-Sepharose, Blue Sepharose CL-6B, and Sephacryl S-200 column chromatography. Purified CTBP had a sedimentation coefficient of 4.7 S, Stokes radius of 32.5A, and calculated molecular weight of 58,000. The apparently homogeneous protein consisted of a single polypeptide chain with Mr of 58,000 as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Scatchard analysis of T3 binding showed that NADPH increases maximal binding capacity without changes in the affinity constant (Ka = 2.43 X 10(9) M-1). Double reciprocal analysis of NADPH and binding capacity gave maximal binding capacity of 16,400 pmol/mg of CTBP, Mr = 58,000. The order of affinity of iodothyronine analogues to purified CTBP was as follows: L-T3 = D-T3 greater than triiodothyroacetic acid greater than L-thyroxine. [125I]T3 bound to purified CTBP spontaneously dissociated from CTBP at 20 degrees C (t 1/2 = 22 min) in the absence of NADPH, whereas the dissociation was not observed in the presence of NADPH. The optimal pH for T3 binding was 7.2-7.5 Na+, K+, Ca2+, and Mg2+ (0-200 mM) did not influence T3 binding to CTBP. The purified CTBP did not bind to DNA and was not adsorbed to concanavalin A-Sepharose. PMID- 2925672 TI - Evidence for the presence of two active forms of cytosolic 3,5,3'-triiodo-L thyronine (T3)-binding protein (CTBP) in rat kidney. Specialized functions of two CTBPs in intracellular T3 translocation. AB - Cytosolic NADPH-dependent 3,5,3'-triiodo-L-thyronine (T3)-binding protein (CTBP) purified from rat kidney was further characterized in its T3 binding and its interaction with nuclei. Pretreatment of the CTBP with NADP induced dithiothreitol (DTT)-dependent T3 binding. The DTT-dependent T3 binding was increased by NADP in a concentration-dependent manner, and the maximal binding was obtained by 0.1 microM NADP. Higher concentrations of NADP (more than 0.1 microM), however, reduced T3 binding. NAD also induced DTT-dependent T3 binding, but was very low compared to that induced by NADP. NADPH and NADH did not produce DTT-dependent T3 binding. This NADP-activated, DTT-dependent T3 binding was characterized as follows: Ka for T3 binding was 1.8 x 10(9) M-1, and the maximal binding capacity was 15,000 pmol/mg of protein in the CTBP activated by 0.1 microM NADP. The molecular weight of the CTBP was 58,000 (4.7 S). A complex of [125I]T3 and CTBP (NADP.DTT.CTBP.[125I]T3), which was made from the CTBP pretreated with NADP and DTT, did not bind to DNA. However, the complex bound to the nuclei prepared from rat kidney. Treatment of the nuclei with 0.38 M KCl and with DNase I did not lead to loss of the binding activity for the complex. Treatment of nuclei with 0.5 M NaCl led to the loss of the activity for binding the complex. A complex of [125I]T3 and NADPH-activated CTBP did not bind these nuclear preparations. These results suggested that the active form of CTBP is present in two different forms: one is NADPH-activated, which plays a role as a reservoir for cytoplasmic T3, and the other is NADP-activated, which plays a role as a T3 carrier protein that transfers T3 from cytoplasm to nucleus. PMID- 2925673 TI - Transport and phosphorylation of choline in higher plant cells. Phosphorus-31 nuclear magnetic resonance studies. AB - When sycamore cells were suspended in basal medium containing choline, the latter was taken up by the cells very rapidly. A facilitated diffusion system appertained at low concentrations of choline and exhibited Michaelis-Menten kinetics. At higher choline concentrations simple diffusion appeared to be the principal mode of uptake. Addition of choline to the perfusate of compressed sycamore cells monitored by 31P NMR spectroscopy resulted in a dramatic accumulation of P-choline in the cytoplasmic compartment containing choline kinase and not in the vacuole. The total accumulation of P-choline over a 10-h period exhibited Michaelis-Menten kinetics. During this period, in the absence of Pi in the perfusion medium there was a marked depletion of glucose-6-P, and the cytoplasmic Pi resonance disappeared almost completely. When a threshold of cytoplasmic Pi was attained, the phosphorylation of choline was sustained by the continuous release of Pi from the vacuole although at a much lower rate. However, when 100 microM inorganic phosphate was present in the perfusion medium, externally added Pi was preferentially used to sustain P-choline synthesis. It is clear, therefore, that cytosolic choline kinase associated with a carrier mediated transport system for choline uptake appeared as effective systems for continuously trapping cytoplasmic Pi including vacuolar Pi entering the cytoplasm. PMID- 2925674 TI - Polypeptide structure of germin as deduced from cDNA sequencing. AB - Synthesis of a relatively rare glycoprotein (germin) signals the onset of growth in germinating wheat embryos. Germin mRNA (1075 nucleotide residues) has an 85 residue 5'-untranslated sequence, a 69-residue sequence that can encode a 23 residue signal-peptide sequence, a 603-residue sequence that can encode a 201 residue mature-protein sequence, and a 318-residue 3'-untranslated sequence that begins with a UAA-terminator codon, ends with a 63-residue polyadenylate tract, and has three polyadenylation (and other, related) signals (AAUAAN etc.). One polyadenylation signal is just 9 nucleotides from the polyadenylation site, the shortest stretch of nucleotides yet found between polyadenylation signal and site in any animal or plant mRNA. The mature-protein coding sequence in germin mRNA contains an unusually high proportion (87%) of G + C in the third positions of its codons. The amino acid sequence of germin does not have extensive internal homologies or repetitions, and it is not characterized by regions of unusually high charge density, as is nucleoplasmin, another water-soluble homopentameric protein with otherwise closely related structural properties. Germin does, however, contain a stretch of 34 uncharged amino acid residues and these may possibly mediate its homopentameric structure and its remarkable resistance to enzymic proteolysis. In view of a possible association of germin with cellular membranes, the most interesting relatedness of the germin sequence to the sequences of other proteins is an 80% homology between a decapeptide sequence in mature germin and a decapeptide sequence in Escherichia coli glycerol-3-phosphate acyltransferase. The relation of germin-gene structure to overall gene regulation during early plant growth is discussed. PMID- 2925675 TI - A newly synthesized selective casein kinase I inhibitor, N-(2-aminoethyl)-5 chloroisoquinoline-8-sulfonamide, and affinity purification of casein kinase I from bovine testis. AB - When screening various isoquinolinesulfonamide compounds which we synthesized, CKI-7, N-(2-amino-ethyl)-5-chloroisoquinoline-8-sulfonamide, was found to have a potent inhibitory action against casein kinase I and a much weaker effect on casein kinase II and other protein kinases. Kinetic analysis indicated that CKI-7 inhibited casein kinase I competitively with respect to ATP and that the Ki values were 8.5 microM for casein kinase I and 70 microM for casein kinase II. An affinity chromatography absorbent was synthesized by coupling CKI-8 (1-(5 chloroisoquinoline-8-sulfonyl], a derivative of CKI-7, to cyanogen bromide activated Sepharose 4B. Partially purified casein kinase I from bovine testis was subjected to affinity chromatography. Analysis of the purified casein kinase I by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate revealed a single band with molecular weight 37,000. These newly synthesized compounds, CKI-7 and CKI-8, should serve as useful tools for elucidating the biological significance of casein kinase I-mediated reactions. PMID- 2925676 TI - Secondary structure of diphtheria toxin and its fragments interacting with acidic liposomes studied by polarized infrared spectroscopy. AB - We used infrared attenuated total reflection spectroscopy to study the structure of diphtheria toxin (DT) and its fragments A, B, CB1, and CB4 as a function of the pH in the absence and in the presence of phospholipid vesicles. Binding of DT to asolectin or DL-alpha-dipalmitoylphosphatidylcholine-DL-alpha dipalmitoylphosphatidic acid liposomes at pH 7.3 results in a 10% increase in its alpha-helix content. At pH 4, in the presence of liposomes, the secondary structure of DT is characterized by the appearance of a beta-sheet structure with strengthened hydrogen bonds which did not exist before pH lowering. DT fragment B displays little conformational change upon pH lowering in the presence of liposomes. However, the alpha-helix content of CB1 increases by 10%, and polarization measurements indicate that the alpha-helices of CB1 at pH 4 are oriented parallel to the lipid acyl chains. On the other hand, the alpha-helix content of CB4 decreases dramatically while the low frequency beta-sheet content increases. Dichroism measurements demonstrate that this sheet lies close to a parallel to the bilayer surface. The fragment A of DT experiences a large conformational change upon pH lowering and binds to the liposome membrane even in the absence of DT fragment B. The conformational modification of DT fragment A is fully reversed when pH is brought back to 7.3. PMID- 2925677 TI - Mouse primase p49 subunit molecular cloning indicates conserved and divergent regions. AB - Primase is a specialized RNA polymerase that synthesizes RNA primers for initiation of DNA synthesis. A full cDNA clone of the p49 subunit of mouse primase, a heterodimeric enzyme, has been isolated using a primase p49-specific polyclonal antibody to screen a lambda gt11 mouse cDNA expression library. The cDNA indicated the subunit is a 417-amino acid polypeptide with a calculated molecular mass of 49,295 daltons. The p49 mRNA is approximately 1500 nucleotides long with a 5'-untranslated region of 74 nucleotides and a 3'-untranslated region of 200 nucleotides. Comparison with a similar sized primase subunit from yeast showed highly conserved amino acid sequences in the N-terminal halves of the polypeptides and included a potential metal-binding domain suggesting the functional importance of this region for DNA binding. In contrast, the 3' portion of the cDNA has rapidly diverged in nucleotide sequence, as primase mRNA can be detected in mouse and rat cells with a 3' probe (including coding and noncoding) but not in RNA from hamster or human cells. A full-length cDNA probe detected mRNA from hamster and human cell lines, indicating a conserved 5' portion and divergent 3' region of the expressed gene. The rapid divergence may be related to the species-specific protein interactions found for the DNA polymerase alpha primase complex. The mRNA is detected in proliferating but not in quiescent cells consistent with its function in DNA replication. PMID- 2925678 TI - Characterization of novel glycolipids from the giant cockroach (Blaberus colosseus). AB - A novel class of glycolipids, assigned the trivial name blaberosides, was isolated from whole head tissues of the giant cockroach (Blaberus colosseus). The class consists of two closely related families, blaberoside I and blaberoside II, each containing species differing by 26 atomic mass units. The structure of these gentiobiose-based glycoglycerolipids was elucidated by chromatographic behavior, nuclear magnetic resonance spectroscopy, mass spectrometry, and analysis of chemical degradation products and derivatives. Species in the blaberoside I family have been identified as 2-O-[6'-O-(6"-O-3-hydroxy-11-eicosenoyl-beta-D glucopyranosyl)-bet a-D- glucopyranosyl]-3-(hexadecyloxy)-1-(3-hydroxy-11 eicosenoyl)-1,2-p ropanediol (blaberoside Ia) and 2-O-[6'-O-(6"-O-3-hydroxy-11 eicosenoyl-beta-D-glucopyranosyl)-bet a- D-glucopyranosyl]-3-(6-octadeceloxy)-1 (3-hydroxy-11-eicosenoyl )-1,2- propanediol (blaberoside Ib). Two smaller homologs of the blaberoside II family were discerned to be 2-O-[6'-O-(6"-O-3 hydroxy-11- eicosenoyl-beta-D-glucopyranosyl)-beta-D-glucopyranosyl]-3-(hex ade cyloxy)- 1,2-propanediol (blaberoside IIa), and 2-O-[6'-O-(6"-O-3-hydroxy-11 eicosenoyl-beta-D- glucopyranosyl)-beta-D-glucopyranosyl]-3-(4-octadeceloxy)-1,2 prop anediol (blaberoside IIb). These compounds are unique because they are animal origin glyceroglycolipids with a highly flexible gentiobiose backbone, and a beta-linkage of the carbohydrate to the glycerol ether at the 2 position rather than the usual 1 position. PMID- 2925679 TI - Lateral diffusion as a rate-limiting step in ubiquinone-mediated mitochondrial electron transport. AB - Data are presented which indicate that the diffusion-based collisions of ubiquinone with its redox partners in the mitochondrial inner membrane are a rate limiting step for maximum (uncoupled) rates of succinate-linked electron transport. Data were obtained from experimental analysis of a comparison of the apparent activation energies of lateral diffusion rates, collision frequencies, and electron transport rates in native and protein-diluted (phospholipid enriched) inner membranes. Diffusion coefficients for Complex III (ubiquinol:cytochrome c oxidoreductase) and ubiquinone redox components were determined as a function of temperature using fluorescence recovery after photobleaching, and collision frequencies of appropriate redox partners were subsequently calculated. The data reveal that 1) the apparent activation energies for both diffusion and electron transport were highest in the native inner membrane and decreased with decreasing protein density, 2) the apparent activation energy for the diffusion step of ubiquinone made up the most significant portion of the activation energy for the overall kinetic activity, i.e. electron transport steps plus the diffusion steps, 3) the apparent activation energies for both diffusion and electron transport decreased in a proportionate manner as the membrane protein density was decreased, and 4) Arrhenius plots of the ratio of experimental electron transport productive collisions (turnovers) to calculated theoretically predicted, diffusion-based collisions for ubiquinone with its redox partners had little or no temperature dependence, indicating that as temperature increases, increases in electron transport rate are accounted for by the increases in diffusion-based collisions. These data support the Random Collision Model of mitochondrial electron transport in which the rates of diffusion and appropriate concentrations of redox components limit the maximum rates of electron transport in the inner membrane. PMID- 2925680 TI - Mannose processing is an important determinant in the assembly of phosphorylated high mannose-type oligosaccharides. AB - Phosphorylation of the high mannose-type oligosaccharides attached to newly synthesized acid hydrolases occurs in two sequential steps within the endoplasmic reticulum and the Golgi apparatus, and the products generated at the two sites differ with respect to the location of the phosphorylated mannose residue. To investigate the mechanism of this two-step phosphorylation, biosynthesis of the Man-6-P recognition marker was studied in class E Thy-1- and J774 cells metabolically labeled with [2-3H]mannose. Class E Thy-1- cells produce truncated high mannose oligosaccharides that lack 4 mannose residues from the alpha 1,6 branch of the core beta-linked mannose residue; three of the missing residues are potential phosphorylation sites. Acid hydrolases produced by these mutant cells were phosphorylated on the alpha 1,3-branch of the truncated oligosaccharide even when transport to the Golgi apparatus was inhibited. J774 cells produce normal high mannose oligosaccharides, but they secrete a large percentage of their newly synthesized acid hydrolases. The secreted enzymes contained primarily diphosphorylated units in which a phosphate was positioned to both the alpha 1,3- and alpha 1,6-branches of the core beta-linked mannose. J774 cells treated with deoxymannojirimycin continued to phosphorylate and to secrete acid hydrolases. The secreted hydrolases, however, contained only monophosphorylated oligosaccharides in which the phosphate was restricted to the alpha 1,6-branch. These results indicate that mannose residues within high mannose oligosaccharides impose constraints on the phosphorylation of their composite structures. We conclude that the two-step phosphorylation occurs as a result of a common phosphotransferase at both the pre-Golgi and Golgi locations and a change in the conformation of the oligosaccharides attached to the acid hydrolases through the action of Golgi-associated alpha-mannosidase I. PMID- 2925681 TI - Characterization of a cDNA encoding a manganese peroxidase, from the lignin degrading basidiomycete Phanerochaete chrysosporium. AB - A cDNA clone of a manganese peroxidase (MnP) from Phanerochaete chrysosporium was isolated and characterized. The cDNA contains 1314 nucleotides excluding the poly(A) tail and the coding region has 68% G + C content. The deduced mature MnP protein contains 357 amino acids and is preceded by a 21-amino acid leader sequence. The experimentally determined N-terminal sequence of the purified MnP-1 protein, pI = 4.9, corresponds to the deduced N-terminal sequence of the gene. The Mr of the mature MnP-1 deduced from the cDNA is 37,439, which is approximately 81.4% of the experimentally determined molecular weight. The difference is due to glycosylation and a single potential N-glycosylation site with the general sequence Asn-X-Thr/Ser is present in the deduced MnP-1 sequence. Consistent with the peroxidase mechanism of MnP, the proximal histidine, the distal histidine, and the distal arginine are all conserved and regions flanking these residues display homology with other peroxidases. Northern blot analysis indicates that MnP expression is controlled by nutrient nitrogen at the level of transcription. Southern blot hybridization analysis suggests that MnP-1 is a member of a family of MnP genes. PMID- 2925682 TI - Mammalian glycinamide ribonucleotide transformylase. Kinetic mechanism and associated de novo purine biosynthetic activities. AB - Glycinamide ribonucleotide transformylase catalyzes the conversion of glycinamide ribonucleotide and 10-formyltetrahydrofolate to formylglycinamide ribonucleotide and tetrahydrofolate. The enzyme purified from the murine lymphoma cell line L5178Y also catalyzes two other de novo purine biosynthetic activities, glycinamide ribonucleotide synthetase and aminoimidazole ribonucleotide synthetase. The transformylase reaction shows a 1:1 stoichiometry for substrate utilization and an optimum rate between pH 7.9 and 8.3. Initial velocity and dead end inhibition patterns indicate that the kinetic mechanism of the transformylation reaction is ordered-sequential, with 10-formyltetrahydrofolate binding first. alpha, beta-Hydroxyacetamide ribonucleotide (alpha, beta-N (hydroxyacetyl)-D-ribofuranosylamine) is shown to be an inhibitor of the transformylase, competitive against glycinamide ribonucleotide. PMID- 2925683 TI - Quantitative analysis of collagen expression in embryonic chick chondrocytes having different developmental fates. AB - A quantitative determination of collagen expression was carried out in cultured chondrocytes obtained from a tissue that undergoes endochondral bone replacement (ventral vertebra) and one that does not (caudal sterna). The "short chain" collagen, type X is only expressed in the former while the other "short chain" collagen type IX, was primarily expressed in the latter. These two tissues also differ in that vertebral chondrocytes express moderate levels of both type I procollagen mRNAs which were translated into full length procollagen chains both in vivo and in vitro, while caudal sternal chondrocytes did not. The percent of collagen synthesis was about 50% in both cell types, but sternal cells expressed twice as much collagen as vertebral cells even though type II procollagen was more efficiently processed to alpha-chains in vertebral chondrocytes than in sternal chondrocytes. The number of type II procollagen mRNA molecules/cell was found to be about 2300 in vertebral chondrocytes and about 8000 in sternal cells, in good agreement with the results reported by Kravis and Upholt (Kravis, D., and Upholt, W. B. (1985) Dev. Biol. 108, 164-172). There were about 630 copies of type I procollagen mRNAs with an alpha 1/alpha 2 ratio of 1.6 in vertebral chondrocytes compared with 5100 copies and an alpha 1/alpha 2 ratio of 2.2 in osteoblasts, and less than 40 copies in sternal cells. Since the rate of type I collagen chain synthesis was 50 times greater in osteoblasts than in vertebral cells, type I procollagen mRNAs were about six times less efficiently translated in vertebral cells than in osteoblasts. The type I mRNAs in vertebral chondrocytes were polyadenylated and had 5' ends that were identical in osteoblasts, fibroblasts, and myoblasts. Moreover, type I mRNAs isolated from vertebral chondrocytes were translated into full length preprocollagen chains in vitro in rabbit reticulocyte lysates. Thus, chondrocytes isolated from cartilage tissues with different developmental fates differed quantitatively and qualitatively in total collagen synthesis, procollagen processing, and distribution of collagen types. PMID- 2925685 TI - Characterization of a novel glycoprotein isolated from the basement membrane matrix of the Engelbreth-Holm-Swarm tumor. AB - A previously undescribed protein has been isolated and purified from the extracellular matrix of the Engelbreth-Holm-Swarm (EHS) tumor, a murine tumor that synthesizes an extensive matrix composed of basement membrane molecules. Molecular characterization of the molecule determined that it is a glycoprotein with internal disulfide bonds and an isoelectric point of 6.0. Electrophoretic mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that the glycoprotein migrated as a diffuse band with a molecular weight of approximately 72,000-80,000. The amino acid composition was significantly different from known basement membrane components. Polyclonal antibodies that specifically recognize the glycoprotein localized it to the kidney glomerular basement membrane. These antibodies did not cross-react with either known basement membrane components (laminin, type IV collagen, and heparan sulfate proteoglycan), with 70K "culture shock" protein or with components of normal mouse serum (including mouse transferrin, albumin, or alpha-fetoprotein), when analyzed by "Western" immunoblots. Our data indicate that the glycoprotein is synthesized by the EHS tumor cells and is present at relatively high levels in the EHS tumor matrix. PMID- 2925684 TI - Further characterization of eukaryotic initiation factor 5 from rabbit reticulocytes. Immunochemical characterization and phosphorylation by casein kinase II. AB - Eukaryotic initiation factor (eIF)-5, isolated from rabbit reticulocyte lysates, is a monomeric protein of Mr = 58,000-62,000. Immunochemical methods were employed to identify eIF-5 in crude cell lysates. Antisera against purified denatured eIF-5 were prepared in rabbits and characterized by immunoblotting and immunoprecipitation techniques using native and denatured eIF-5 as antigens. Monospecific antibodies to denatured eIF-5 were affinity-purified using eIF-5 blotted onto aminophenylthioether paper. Rabbit reticulocytes, HeLa cells and mouse L cells were lysed directly into a denaturing buffer containing 3% sodium dodecyl sulfate. The denatured proteins were analyzed by polyacrylamide gel electrophoresis followed by immunoblotting with anti-eIF-5 antibodies. With each lysate, one major immunoreactive polypeptide was observed whose molecular weight corresponded to that of purified eIF-5 (Mr = 58,000-62,000). No degradation products or precursor forms of molecular weight higher than 62,000 were detected in any lysate. These results indicate that isolated eIF-5 is the same size as that found in crude lysates. Additional characterization of eIF-5 indicates that purified eIF-5 can be phosphorylated at serine residues in vitro by casein kinase II. Furthermore, in vitro phosphorylated eIF-5 retains full biological activity in catalyzing the joining of 60 S ribosomal subunits to a preformed 40 S ribosomal initiation complex to form an 80 S initiation complex. Based on its specific activity, we demonstrate that 1 pmol of rabbit reticulocyte eIF-5 mediates the formation of approximately 180 pmol of 80 S initiation complex under the conditions of in vitro initiation reactions. PMID- 2925686 TI - Retinoic acid acylation (retinoylation) of a nuclear protein in the human acute myeloid leukemia cell line HL60. AB - all-trans-Retinoic acid is a potent inducer in vitro of the differentiation of the human acute myeloid leukemia cell line HL60 and of fresh cells from patients with acute promyelocytic leukemia. The recent discovery of nuclear retinoic acid receptors provides a basis for understanding how retinoic acid acts at the genetic level. We have now found that retinoic acid is incorporated into HL60 cells in a form that is not removed by extraction with CHCl3:CH3OH. About 90% of this labeled retinoic acid is trichloroacetic acid-soluble after digestion with proteinase K or after hydrolysis with either NH2OH or CH3OH:KOH under mild conditions. Methyl retinoate is the major product of hydrolysis with CH3OH:KOH. These results are consistent with retinoylation of protein with the formation of an ester, probably thioester, bond. The extent of the retinoylation of HL60 protein is dependent on both time and retinoic acid concentration. A major fraction of the retinoylation is of protein that has a molecular mass of 55 kDa after reduction with dithiothreitol. On two-dimensional gels, the retinoylated protein has a pI of about 4.9 and a molecular mass of 55-60 kDa. These characteristics and its localization in the cell nucleus are consistent with retinoylation of the HL60 nuclear retinoic acid receptor or a closely related protein. PMID- 2925687 TI - Induction of transforming growth factor-alpha expression in human keratinocytes by phorbol esters. AB - Exposure of cultured human epidermal keratinocytes to the protein kinase C (Ca2+- and phospholipid-dependent protein kinase)-activating phorbol esters 12-O tetradecanoylphorbol-13-acetate (TPA) or 4-beta-phorbol-12,13-didecanoate markedly enhanced accumulation of transforming growth factor-alpha (TGF-alpha) mRNA and secretion of TGF-alpha protein. The nonactivating phorbol ester, 4-alpha phorbol 12,13-didecanoate, had no effect. In the absence of exogenous growth factors, confluent cultures of keratinocytes express low or undetectable levels of TGF-alpha mRNA and protein. While TPA and epidermal growth factor treatment of keratinocyte cultures deprived of growth factors both induced TGF-alpha mRNA expression, maximum induction by TPA is 5-fold greater than epidermal growth factor. Furthermore, the addition of epidermal growth factor did not enhance TPA mediated induction of TGF-alpha mRNA expression. Under these experimental conditions, TPA increased levels of secreted TGF-alpha protein by 20-fold at 24 h. Concentration dependence and kinetic studies of TGF-alpha expression showed that TPA (greater than or equal to 1 ng/ml) induced accumulation of TGF-alpha mRNA with an optimum concentration of 10 ng/ml. TGF-alpha mRNA expression increased within 1 h following TPA treatment (10 ng/ml) and peaked at 5 h. At 24 h, TPA-treated cultures still expressed elevated levels of TGF-alpha mRNA (1.7 fold). Protein secretion into the medium was enhanced 2-fold (5 h) to 3-fold (24 h) by TPA treatment of keratinocyte cultures containing growth factors. Prolonged pretreatment (24 h) of keratinocyte cultures with TPA caused marked desensitization of TGF-alpha mRNA expression to repeated stimulation by phorbol ester. The synthetic diacylglycerol, 1,2-sn-dioctanoylglycerol, enhanced levels of TGF-alpha transcription and secretion of TGF-alpha protein. The rate of TGF alpha mRNA accumulation peaked and declined earlier for 1,2-sn-dioctanoylglycerol compared to TPA. 1,2-sn-Dioctanoylglycerol (50 micrograms/ml) increased production and secretion of TGF-alpha protein, but less than TPA treatment. An inhibitor of protein kinase C, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, also inhibited 1,2-sn-dioctanoylglycerol-mediated accumulation of TGF-alpha mRNA. Cycloheximide failed to inhibit TGF-alpha mRNA expression induced by TPA and, when added alone to keratinocyte cultures, significantly enhanced TGF-alpha mRNA accumulation. Actinomycin D abrogated transcriptional activation of TGF-alpha mRNA by TPA. These studies suggest that activation of protein kinase C by active phorbol esters or diacylglycerols is responsible, at least in part, for TGF-alpha gene expression.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2925688 TI - Transcriptional regulatory sequences of the housekeeping gene for human triosephosphate isomerase. AB - To examine the functional organization of the human triosephosphate isomerase (TPI) promoter, deletion, insertion, and linker scanning mutations were introduced into the TPI promoter of hybrid TPI/beta-globin genes. These genes were transiently expressed in mouse L and human HeLa cells, and the effect of each mutation on the frequency and position of transcription initiation was assayed by S1 nuclease transcript mapping. Multiple positive regulatory elements reside between positions -595 and +1 in L cells and -920 and -7 in HeLa cells and coordinately promote maximum hybrid gene transcription. These elements include an array of GC boxes (positions -126 to -48) that variably conform to the consensus Sp1-binding site, and a canonical TATA box (positions -27 to -21) that is essential for detectable levels of transcription. In an additive yet position dependent fashion, the GC boxes function in cis to the TATA box to control both the frequency and position of transcription initiation. Additional positive elements reside upstream of position -131 and are required for full promoter function. Also, an inhibitory element(s) residing between position -7200 and either -2800 in L cells or -920 in HeLa cells reduces transcription approximately 7-fold relative to the level of transcription achieved with the maximally active promoter. PMID- 2925689 TI - A glycosomal protein (p60) which is predominantly expressed in procyclic Trypanosoma brucei. Characterization and DNA sequence. AB - Glycosomes are specialized organelles of trypanosomes which contain glycolytic enzymes as their major protein components in Trypanosoma brucei bloodstream form. In the glycosomes of the insect form of T. brucei, additional enzyme activities are found but have not yet been ascribed to a particular protein molecule. In this study, we report the characterization of a 60-kDa glycosomal protein (p60) encoded by a single copy gene which is transcribed into a mRNA of 2.9 kilobases. The gene codes for a protein of 472 amino acids with a molecular mass of 52.5 kDa, suggesting that the mRNA contains large untranslated regions of about 1.4 kilobases. Genomic DNA hybridizations have shown that the gene for p60 is confined to the family of Trypanosomatidae. Sequence comparison confirmed that p60 is not a member of a conserved protein family and does not belong to the group of glycolytic enzymes. p60 is expressed much more strongly in insect form than in bloodstream form trypanosomes. Thus, p60 is the first glycosomal protein observed whose expression is up-regulated during the transition of trypanosomes from the bloodstream to the insect form. The biochemical characterization of p60 demonstrated its capability to bind microtubules and membrane vesicles and to cross-link these structures. These properties might indicate a function in linking glycosomes to the microtubules of the trypanosomal cytoskeleton. However, proteinase K digestion experiments indicate that p60 is not exposed at the outer surface of the glycosomal membrane. The biological role of the microtubule binding capability of p60 remains unclear, whereas its membrane binding may be of physiological significance inside the glycosome. PMID- 2925690 TI - Mechanism of phosphorylation in the lumen of the Golgi apparatus. Translocation of adenosine 5'-triphosphate into Golgi vesicles from rat liver and mammary gland. AB - The occurrence of phosphorylated secretory proteins such as caseins and vitellogenin and the recent characterization of phosphorylated proteoglycans, in the xylose and protein core, has raised the question of where in the cell and how this phosphorylation occurs. Previous studies have described a casein kinase activity in the lumen of the Golgi apparatus and this organelle as the site of xylose addition to the protein core of proteoglycans. We now report the translocation in vitro of ATP into the lumen of rat liver and mammary gland Golgi vesicles which are sealed and have the same membrane topographical orientation as in vivo. The entire ATP molecule was translocated into the lumen of the Golgi vesicles; this was established by using ATP radiolabeled with tritium in the adenine and gamma-32P. Translocation was temperature dependent and saturable, with an apparent Km of 0.9 microM and Vmax of 58 pmol/mg protein/min. Preliminary evidence suggests that translocation of ATP into the vesicles' lumen is coupled to exit of AMP from the lumen. Following translocation of ATP into the lumen of the vesicles, proteins were phosphorylated. PMID- 2925691 TI - Factor C from rabbit liver. A new poly(dC) and poly[d(G-C)] template-selective stimulatory protein of DNA polymerases. AB - We have undertaken a search for mammalian DNA-binding proteins that enhance the activity of DNA polymerases in a template sequence-specific fashion. In this paper, we report the extensive purification and characterization of a new DNA binding protein from rabbit liver that selectively stimulates DNA polymerases to copy synthetic poly[d(G-C)] and the poly(dC) strand of poly(dC).poly(dG) as well as single-stranded natural DNA that contains stretches of oligo(dC). The enhancing protein, a polypeptide of 65 kDa designated factor C, stimulates the copying of the two synthetic templates by Escherichia coli DNA polymerase I, Micrococcus luteus polymerase, and eukaryotic DNA polymerases alpha and beta, but not by avian myeloblastosis virus polymerase. Factor C, however, does not affect utilization by these polymerases of the poly(dG) strand of poly(dC).poly(dG), of poly(dC) primed by oligo(dG), or of poly(dA).poly(dT) and poly[d(A-T)]. With polymerase I, Michaelis constants (Km) of poly[d(G-C)] and of the poly(dC) strand of poly(dC).poly(dG) are decreased by factor C 37- and 4.7-fold, respectively, whereas maximum velocity (Vmax) remains unchanged. By contrast, neither the Km value of the poly(dG) strand of poly(dC).poly(dG) nor the Vmax value with this template is altered by factor C. Rates of copying of activated DNA, denatured DNA, or singly primed M13 DNA are not affected significantly by factor C. However, primer extension analysis of the copying of recombinant M13N4 DNA that contains runs of oligo(dC) within an inserted thymidine kinase gene shows that factor C increases processivity by specifically augmenting the efficiency at which polymerase I traverses the oligo(dC) stretches. Direct binding of factor C to denatured DNA is indicated by retention of the protein-DNA complex on columns of DEAE-cellulose. Binding of factor C to poly[d(G-C)] is demonstrated by the specific adsorption of the enhancing protein to columns of poly[d(G-C)] Sepharose. We propose that by binding to poly[d(G-C)] and to poly(dC).poly(dG), factor C enables tighter binding of some DNA polymerases to these templates and facilitates enzymatic activity. PMID- 2925692 TI - The QUEST system for quantitative analysis of two-dimensional gels. AB - The strategies and methods used by the QUEST system for two-dimensional gel analysis are described, and the performance of the system is evaluated. Radiolabeled proteins, resolved on two-dimensional gels and detected using calibrated exposures to film, are quantified in units of disintegrations per minute or as a fraction of the total protein radioactivity applied to the gel. Spot quantitation and resolution of overlapping spots is performed by two dimensional gaussian fitting. Pattern matching is carried out for groups of gels called matchsets, and within each matchset every gel is matched to every other gel. During the matching process, spots are automatically added to each pattern at positions where unmatched spots were detected in other patterns. This results in enhanced accuracy for both spot detection and for matching. The spot fitting procedure is repeated after matching. Tests show that up to 97% of spots in each pattern can be matched and that fewer than 1% of the spots are matched inconsistently. Approximately 2000 proteins are detected from typical gels. Of these 1600 are high quality spots. Tests to measure the coefficient of variation of spot quantitation versus spot quality show that the average coefficient of variation for high quality spots is 21%. The intensities of the detected proteins range from 4 to 20,000 ppm of total protein synthesis. The QUEST analysis system has been used to build a quantitative database for the proteins of normal and transformed REF52 cells, as presented in the accompanying reports (Garrels, J., and Franza, B. R., Jr. (1989) J. Biol. Chem. 264, 5283-5298, 5299-5312). PMID- 2925694 TI - Demographic components of seasonality of pregnancy. AB - Previous studies of the seasonality of pregnancy and birth have typically been based on monthly numbers or proportions of pregnancies or births (i.e. their distribution throughout the year) without any explicit accounting of the size of the population actually at risk of pregnancy by month. From data on monthly populations at risk and monthly probabilities of pregnancy this paper determines the relative contribution of each component to the monthly distribution of pregnancies. The data come from the National Survey of Family Growth, Cycle III. While there is some seasonality in the size of the at-risk population, it contributes little to the overall monthly variation of pregnancy, which is determined mainly by seasonality of pregnancy probability (fecundability). PMID- 2925693 TI - The REF52 protein database. Methods of database construction and analysis using the QUEST system and characterizations of protein patterns from proliferating and quiescent REF52 cells. AB - The construction and analysis of protein databases using the QUEST system is described, and the REF52 protein database is presented. A protein database provides the means to store and compare quantitative and descriptive data for up to 2000 proteins from many experiments that employ computer-analyzed two dimensional gel electrophoresis. The QUEST system provides the tools to manage, analyze, and communicate these data. The REF52 database contains experiments with normal and transformed rat cell lines. In this report, many of the proteins on the REF52 map are identified by name, by subcellular localization, and by mode of post-translational modification. The quantitative experiments analyzed and compared here include 1) a study of the quantitative reproducibility of the analysis system, 2) a study of the clonal reproducibility of REF52 cells, 3) a study of growth-related changes in REF52 cells, and 4) a study of the effects of labeling cells for varying lengths of time. Of the proteins analyzed from REF52 cells, 10% are nuclear, 6% are phosphoproteins, and 4% are mannose-labeled glycoproteins. The mannose-labeled proteins are more prominent in patterns from quiescent cells, while the synthesis of cytoskeletal proteins is generally repressed at quiescence. A small set of proteins, selected for elevated rates of synthesis is generally repressed at quiescence. A small set of proteins, selected for elevated rates of synthesis in quiescent versus proliferating cells includes one of the tropomyosin isoforms, a myosin light chain isoform, and several prominent glycoproteins. These proteins are thought to be characteristic of the differentiated state of untransformed REF52 cells. Proteins induced early versus late after refeeding quiescent cells show very different patterns of growth regulation. These studies lay the foundations of the REF52 database and provide information needed to interpret the experiments with transformed REF52 cells, which are reported in the accompanying paper (Garrels, J., and Franza, B. R., Jr. (1989) J. Biol. Chem. 264, 5299-5312). PMID- 2925695 TI - Working status and stress of middle class women of Calcutta. AB - In India an increase in female employment outside the home has occurred during the last few decades, especially in urban areas. A working woman may face difficulties in attempting to fulfil the demands of both worlds, at home and outside, while a housewife may feel tired and irritated with her household chores and financial dependence. All these may cause stress for these groups of women. The present study compares a group of working mothers with their non-working counterparts with respect to: (a) stress level, measured in terms of their anxiety score; and (b) certain general indicators of health including a broad measure of stress. The results show that anxiety and health scores of the two groups of women are similar. Further, the health score and anxiety score seem to be correlated, more clearly among the working mothers. PMID- 2925696 TI - Fertility and child mortality in rural Ethiopia: Gondar and Hararge regions. AB - This paper presents fertility and child mortality estimates for agricultural households of the Gondar and Hararge regions, based on the 1981 Rural Demographic Survey. The study shows that fertility and child mortality are quite high in both regions as in the rest of the country. However, Hararge has significantly higher mean parity and child mortality than Gondar. PMID- 2925697 TI - Sociodemographic differentials in mortality during the 1974-75 famine in a rural area of Bangladesh. AB - This study investigates the socio-demographic differentials in mortality during the 1974-75 famine in a rural area of Bangladesh. It is based on household socioeconomic information collected in the 1974 census and registration data on births, deaths and migrations for the period 1974-79 from the Demographic Surveillance System of the International Centre for Diarrhoeal Disease Research, Bangladesh. Ownership of selected household items was considered in the analysis as an indicator of household socioeconomic status. Mortality was 62% higher during the famine period and 31% higher during the post-famine period compared to the non-famine period. The mortality of both the poor and the rich increased during the famine period, by 117% and 28% respectively compared to the non-famine period. The poor suffered significantly in all age groups except 5-14 years, while the rich suffered only for ages 65 and over. Poor males suffered more than poor females except for ages 65 and over, while rich females suffered more than rich males except for ages under 1 year. PMID- 2925699 TI - Contraceptive use patterns in Matlab, Bangladesh: insights from a 1984 survey. AB - An experimental maternal and child health and family planning programme has been in existence in Matlab for almost 10 years. During this time the project has achieved remarkable success in the area of family planning. Based upon a 1984 survey, this study examines the pattern of contraceptive use in the Matlab treatment area, and contrasts it with the regular government programme in the neighbouring comparison area. Important differences between the two areas are observed, with the treatment area characterized by substantially higher levels of current contraceptive use, greater reliance upon temporary methods for birth spacing and, among acceptors of sterilization, more prior experimentation with other methods. In the comparison area lower rates of contraceptive use are observed, with heavy reliance upon tubectomy for limiting family size. The findings suggest that an intensive and innovative family planning programme in rural Bangladesh can achieve success not only in terms of contraceptive prevalence, but can also attract users interested in child spacing and others wanting to limit their family size, by offering the widest range of contraceptive methods. PMID- 2925698 TI - A survey of contraception in five west European countries. AB - In 1984 and 1985, a survey was conducted of 7696 women aged 15-44 living in Italy, France, Great Britain, Spain and the Federal Republic of Germany. The aim of the study was to examine the use of contraceptive methods, the differences in contraceptive use, knowledge of fertility, communication about contraception, motives for choice and the perceptions held by women regarding contraceptive methods, particularly oral contraception. The results show important differences between the countries studied. PMID- 2925700 TI - Recent trends in contraceptive sterilization in Flanders. AB - Elective sterilization started to spread rather late in Flanders. Despite the sharp increase of this contraceptive method since the end of the 1970s, its frequency is still lower than in many neighbouring countries and much lower than in the US and Canada, mainly due to the lag in male sterilization. Further increase in contraceptive sterilization and a greater participation of men is expected in the near future. PMID- 2925701 TI - Nuptiality and fertility in the Dominican Republic. AB - Women in marital unions had more live births than those in consensual unions. The relationship between cumulative fertility and the number of fertile sexual unions is positive for the early childbearing years and negative for the later ones. There is no consistent pattern of relationship between fertility and the sociocultural independent variables for different subgroups according to nuptiality pattern. The relationship between fertility and nuptiality in the Dominican Republic is consistent with that for the Caribbean region. PMID- 2925702 TI - Breast-feeding and post-partum amenorrhoea in Indonesia. AB - The association between breast-feeding patterns and resumption of menses post partum was examined in a prospective study in Indonesia. In order to examine these relationships directly in a longitudinal study, it was first necessary to distinguish among women who experienced infant mortality before menses resumed, women who weaned before menses resumed, and women who had return to menses while breast-feeding. Information on suckling patterns and menstrual status was collected by recall for 444 women at monthly visits for 2 years. Three main breast-feeding variables, minutes per episode, number of episodes per day, number of episodes per night, and other breast-feeding variables were derived for each woman, to give the average nursing pattern up to menses or the end of the study, which-ever came first. While high levels of nursing for each of these three main variables were found to be significantly related to delay in return of menses post-partum, the interactions between more minutes per episode, and more frequent day- and night-time feeds, were found to be the most important factors in the delay in onset of post-partum menstruation in those women whose menses resumed while still nursing or who remained amenorrhoeic and nursing at the end of the study. PMID- 2925703 TI - A reappraisal of some professional attitudes in orthopaedic surgery. PMID- 2925704 TI - Early versus delayed stabilization of femoral fractures. A prospective randomized study. AB - A prospective randomized study comparing the results of early with delayed reduction and stabilization of acute femoral fractures in adults was performed over a two-year period in 178 patients. Only patients who were more than sixty five years old and had a fracture of the hip were excluded. Arterial blood gases, injury-severity score at the time of admission, pulmonary function, days in the hospital, days in the intensive-care unit, and hospital costs were recorded for all patients. The patients were divided into two groups: those who had an isolated fracture of the femur and those who had multiple injuries. When stabilization of the fracture was delayed in the patients who had multiple injuries, the incidence of pulmonary complications (adult respiratory-distress syndrome, fat embolism, and pneumonia) was higher, the hospital stay was longer, and the number of days in the intensive-care unit was increased. The cost of hospital care showed a statistically significant increase for all patients who had delayed treatment of the fracture compared with those who had early stabilization. PMID- 2925705 TI - Difficulties during removal of fluted femoral intramedullary rods. AB - The difficulties that were encountered during removal of a fluted intramedullary femoral rod from six patients were reviewed. The mechanisms of failure included metal breakage at three different locations along the rod or the rod extractor. Three of the six rods were left in place due to difficulties in removal. The design of the fluted intramedullary rod appears to be the main cause of the problem. PMID- 2925706 TI - The effect on gait of lengthening of the medial hamstrings in cerebral palsy. AB - The purpose of this study was to analyze the effect of lengthening of the medial hamstrings on the gait of patients who had spastic cerebral palsy. Thirty-one patients had preoperative and postoperative gait analyses. Standard parameters, such as velocity, cadence, and stride length, were evaluated, as were motion graphs of the hip, knee, and ankle. There was little difference between the preoperative and postoperative mean values for velocity, cadence, and stride length, which were expressed as percentages of normal for the patient's age. The contours of the postoperative motion graphs of the knees changed very little compared with those of the preoperative graphs; when a graph showed restricted motion preoperatively, it did so postoperatively. Although extension of the knee in stance phase improved postoperatively, the improvement was accompanied by decreased flexion of the knee during swing phase. When spasticity of both the hamstrings and the quadriceps was noted on the preoperative electromyogram, motion of the knee in the sagittal plane was markedly restricted. PMID- 2925707 TI - Comparison of short and long thumb-spica casts for non-displaced fractures of the carpal scaphoid. AB - A prospective study was undertaken of fifty-one patients who were randomly assigned to treatment with either a long or a short thumb-spica cast for a non displaced fracture of the carpal scaphoid. The duration of follow-up was at least until union; the average follow-up was twelve months. Twenty-eight fractures were treated with a long thumb-spica cast and twenty-three, with a short thumb-spica cast. The hands that initially were treated with a long thumb-spica cast were placed in a short thumb-spica cast after six weeks. Fractures that initially were treated with a long thumb-spica cast united at an average of 9.5 weeks and those that were maintained in a short thumb-spica cast, at an average of 12.7 weeks. There were no non-unions and two delayed unions in the fractures that initially were treated with a long thumb-spica cast, compared with two non-unions and six delayed unions in those that had only a short thumb-spica cast. Fractures of the proximal or middle third of the carpal scaphoid had a significantly shorter time to union when they were treated initially in a long thumb-spica cast. Fractures of the distal third did well regardless of the type of immobilization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2925708 TI - Wedge resection of the symphysis pubis for the treatment of osteitis pubis. AB - Ten patients had a wedge resection of the symphysis pubis for the treatment of symptoms of osteitis pubis that had been recalcitrant to non-operative treatment for at least six months. Preoperatively, the average duration of symptoms was thirty-two months. The symptoms included a waddling gait and crepitus, pain, and tenderness over the symphysis pubis. The early radiographic signs of the disease were rarefaction of the adjacent pubic bones and widening of the symphysis pubis. Later signs included sclerosis and narrowing of the symphyseal joint space. Pathological examination of the resected joint revealed chronic inflammatory reaction in all patients. At an average of fourteen months postoperatively, all of the patients had marked improvement and were fully active. However, at an average of ninety-two months postoperatively, three of the ten patients were not satisfied with the result. One patient needed bilateral sacro-iliac arthrodesis for pain that was caused by instability. PMID- 2925709 TI - Reflex sympathetic dystrophy of the knee. Treatment using continuous epidural anesthesia. AB - We retrospectively reviewed the cases of fourteen patients who had reflex sympathetic dystrophy of the knee. All fourteen were hospitalized, and epidural block anesthesia was instituted with an indwelling catheter for an average of four days, during which continuous passive motion, manipulation (as necessary), stimulation of muscles, and alternating hot and cold soaks were used. The average length of follow-up was thirty-two months. Eleven patients had complete resolution of the symptoms, two had sufficient intermittent aching with changes in the weather to need medication, and one had no relief. The diagnosis was confirmed if the symptoms were relieved by a lumbar sympathetic block. Pain that was out of proportion to the severity of the injury was the most consistent finding, being present in all fourteen patients. However, variation in clinical severity is characteristic of the syndrome. Eleven of the fourteen patients had had a previous patellar operation. After the onset of the symptoms, nine patients had two or more arthroscopic examinations, without notable findings. All fourteen patients had had extensive physical therapy and medical treatment before the epidural block was performed. PMID- 2925710 TI - The surgical margin in soft-tissue sarcoma. AB - In a retrospective review of 231 patients who were referred to Princess Margaret Hospital because of a soft-tissue sarcoma in an extremity, 100 patients were identified who had no metastases when they were first seen and who had been treated by local resection and adjuvant radiation therapy. Complete data were collected for each patient for the following variables: age; sex; location of the tumor and its size, grade, depth, and compartmental status; chemotherapy; and dose of radiation. The surgical margins were characterized as positive or negative for histological evidence of disease on the basis of an independent review of the pathological and operative reports by a surgeon and a radiation oncologist who were experienced in the management of sarcoma. Cox multivariate analysis was used to determine which of these variables contributed to local recurrence and evidence of systemic disease. Adequacy of the margin of resection was the only variable that was associated with local relapse (p = 0.0004). The size of the tumor (p = 0.0008) was the major determinant of the risk of systemic disease. PMID- 2925711 TI - Arthrodesis of the cervical spine in rheumatoid arthritis. AB - Forty-one patients who had rheumatoid arthritis were treated with a cervical arthrodesis and were followed for a minimum of twenty-three months. Twenty patients had had an isolated atlanto-axial subluxation; five, isolated cranial settling; and four, subaxial subluxation alone. Twenty patients had an atlanto axial arthrodesis; sixteen, an occipitocervical arthrodesis; and five, a posterior arthrodesis of the subaxial spine. In addition, two patients had a transoral odontoidectomy and one, an anterior cervical vertebrectomy. At the latest follow-up, thirty-six (88 per cent) of the patients had osseous union, two had fibrous union but were stable, and three had a non-union. All of the problems with union occurred in the patients who had had an isolated atlanto-axial arthrodesis. Clinically, twenty-seven (66 per cent) of the patients had improved, fourteen were unchanged, and none were worse. The preoperative neurological status remained the same postoperatively in thirty patients (73 per cent) and it improved in eleven (27 per cent). Twenty-one of the twenty-three patients who had had marked pain preoperatively had little or no pain at the latest follow-up. Complications included a transient hemiparesis in one patient, a superficial wound infection in two, displacement of an anterior graft in one, a broken wire in three, and erosion of methylmethacrylate into the outer part of the occipital cortex in one. Four patients died, but not as a result of the operation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2925712 TI - Acute compartment syndrome of the thigh. A spectrum of injury. AB - Twenty-one compartment syndromes of the thigh in seventeen patients were identified for retrospective review. Ten of the compartment syndromes were associated with an ipsilateral femoral fracture; five of these femoral fractures were open. In five patients, the syndrome followed femoral intramedullary stabilization. The remaining eleven syndromes followed blunt trauma to the thigh, prolonged compression by body weight, or vascular injury. The patients who were awake and alert at the time of the examination complained of intense pain in the thigh, and they had neuromuscular deficits. For the patients who could not cooperate with a subjective physical examination because they were under general anesthesia or because of associated injuries, the measurement of compartment pressure assumed a more important diagnostic role. All of the patients had tense swelling of the involved thigh. The predisposing risk factors for the development of compartment syndromes of the thigh, which are common in the multiply injured population, include: systemic hypotension, a history of external compression of the thigh, the use of military antishock trousers, coagulopathy, vascular injury, and trauma to the thigh, with or without a fracture of the femur. In approximately one-half of these patients, a crush syndrome developed, with myoglobinuria, renal failure, and collapse of multiple organ systems. Eight patients (47 per cent) died as a result of multiple injuries. Of the nine patients (ten compartment syndromes) who survived, infection developed at the site of the fasciotomy in six. Follow-up examination revealed marked morbidity, including sensory deficit and motor weakness of the lower extremity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2925713 TI - The effect of lateral meniscectomy on motion of the knee. AB - With the use of a five-degrees-of-freedom testing apparatus, we studied changes in the motion of the knees of cadavera after isolated resection of the lateral meniscus, with section of the anterior cruciate ligament and resection of the medial meniscus. Primary anterior and posterior translations were not affected by lateral meniscectomy. When lateral meniscectomy was done in addition to resection of the anterior cruciate ligament, anterior translation did not increase compared with that measured after isolated section of the anterior cruciate ligament. However, when the means of the paired differences in anterior translation were compared, a significant increase was found. This differed from the results after excision of the medial meniscus and section of the anterior cruciate ligament; in that situation, medial meniscectomy resulted in significantly more anterior translation. PMID- 2925714 TI - A posterior surgical approach to the proximal part of the humerus. AB - At least eight centimeters of the posterior aspect of the proximal region of the humeral diaphyseal cortex can be exposed through the interval between the lateral head of the triceps and the deltoid muscle. No nerves or major blood vessels are exposed in the dissection, although care must be taken to protect the axillary and radial nerves during the exposure. The safety of this approach was confirmed in fourteen upper extremities of seven adult cadavera, and it was used successfully for an excisional biopsy of an osteoid-osteoma in the proximal third of the posterior part of the humeral cortex of an eleven-year-old boy. PMID- 2925715 TI - Prevention of osteoporosis by pulsed electromagnetic fields. AB - Using an animal model, we examined the use of pulsed electromagnetic fields, induced at a physiological frequency and intensity, to prevent the osteoporosis that is concomitant with disuse. By protecting the left ulnae of turkeys from functional loading, we noted a loss of bone of 13.0 per cent compared with the intact contralateral control ulnae over an eight-week experimental period. Using a treatment regimen of one hour per day of pulsed electromagnetic fields, we observed an osteogenic dose-response to induced electrical power, with a maximum osteogenic effect between 0.01 and 0.04 tesla per second. Pulse power levels of more or less than these levels were less effective. The maximum osteogenic response was obtained by a decrease in the level of intracortical remodeling, inhibition of endosteal resorption, and stimulation of both periosteal and endosteal new-bone formation. These data suggest that short daily periods of exposure to appropriate electromagnetic fields can beneficially influence the behavior of the cell populations that are responsible for bone-remodeling, and that there is an effective window of induced electrical power in which bone mass can be controlled in the absence of mechanical loading. PMID- 2925716 TI - Long-term results of triple arthrodesis in Charcot-Marie-Tooth disease. AB - We evaluated sixteen patients who had Charcot-Marie-Tooth disease and had had a total of thirty triple arthrodeses. The average age at the time of operation was fifteen years, and the average length of follow-up was twenty-one years. Of the thirty feet, the result in two (7 per cent) was rated excellent; in five (17 per cent), good; in nine (30 per cent), fair; and in fourteen (47 per cent), poor. Each of the fourteen feet that had a poor result had severe impairment of function and needed an orthosis. Six limbs had an arthrodesis of the ankle for degenerative joint disease. Progressive muscle imbalance resulted in recurrent cavovarus deformity in seven feet that initially had had satisfactory alignment. Degenerative changes of the ankle and joints of the mid-part of the foot were noted radiographically in twenty-three feet. The large number of unsatisfactory long-term results in these patients who had had a triple arthrodesis for deformity of the foot secondary to progressive peripheral neuropathy differs from those in earlier reports on patients who had poliomyelitis, who retained normal sensation and had a permanent, stable muscle imbalance. We believe that triple arthrodesis should be considered only as a salvage procedure in patients who have progressive peripheral neuropathy and should be limited to those who have severe, rigid deformity. PMID- 2925717 TI - Hohmann-Thomasen metatarsal osteotomy for tailor's bunion (bunionette). AB - We used subcapital displacement osteotomy of the fifth metatarsal bone and peg and-hole fixation to treat a tailor's bunion (bunionette) in forty-four feet (twenty-seven patients). The result was good in 86 per cent, fair in 9 per cent, and poor in 5 per cent. All but one of the patients were satisfied with the result. The average medial displacement of the head of the fifth metatarsal was five millimeters. In all feet, secure union was noted in five weeks, and no patient had osteonecrosis of the head of the fifth metatarsal. PMID- 2925718 TI - The use of bacitracin irrigation to prevent infection in postoperative skeletal wounds. An experimental study. AB - In dogs, irrigation of contaminated osseous wounds with bacitracin eliminated clinical evidence of infection and significantly reduced the number of positive cultures and pathological evidence of infection when compared with dogs that received no treatment or irrigation with normal saline solution. The inocula contained more organisms than are introduced into a wound during an elective orthopaedic operation. The use of bacitracin in the prevention of postoperative Staphylococcus aureus infection of bone in humans may be justified. PMID- 2925720 TI - Amputation after tibial fracture: preservation of length by use of a neurovascular island (fillet) flap of the foot. A brief note. PMID- 2925719 TI - The quality of magnetic resonance imaging, as affected by the composition of the halo orthosis. A brief note. PMID- 2925721 TI - Avulsion fracture of the ligamentum teres in a child. A case report. PMID- 2925722 TI - Unilateral angular deformity of the distal end of the femur secondary to a focal fibrous tether. A report of four cases. PMID- 2925723 TI - Aluminum toxicity complicating renal osteodystrophy. A case report. PMID- 2925724 TI - Pseudosarcoma in Paget disease of bone. A case report. PMID- 2925725 TI - Erdheim-Chester disease. A report of three cases. PMID- 2925726 TI - The use of flow cytometry as diagnostic aid in the management of soft tissue tumors. PMID- 2925727 TI - Anterior excision of herniated thoracic discs. PMID- 2925728 TI - A synovial ganglion of the popliteus tendon simulating a parameniscal cyst. Two case reports. PMID- 2925729 TI - The stability of femoral neck fractures and its influence on healing. AB - We measured the stability of fixation in femoral neck fractures treated with von Bahr screws, investigated the influence of impaction and correlated peroperative stability with the clinical results. Stability was measured at operation using a metal probe fitted with strain gauges. Its tip was anchored in the subchondral bone of the femoral head and its lateral end was fixed in the lateral femoral cortex. The shearing force produced by longitudinal compression applied to the foot of the operated leg was recorded. The results in 41 consecutive patients all followed for 30 months, showed that fractures with early loosening or nonunion had all had significantly poorer stability than the fractures that had healed. Impaction improved stability in only 23 out of the 41 fractures; in the others stability had deteriorated or was unchanged. PMID- 2925730 TI - Subchondral screw fixation for femoral neck fractures. AB - We describe a method of internal fixation for femoral neck fractures which has been newly developed to reduce the frequency of early complications. Two cannulated screws are inserted in the axis of the femoral neck to reach into the subchondral bone of the femoral head. The screws are inserted over guide pins and the tip of the screw is self-tapping and designed to provide good anchorage in the femoral head. We used this method in 44 consecutive patients in a prospective study with no exclusions, followed for a minimum of 24 months. All fractures healed within 12 months, and there were no cases of early loosening or nonunion. In four cases, late segmental collapse had developed during the mean follow-up period of 30 months. PMID- 2925732 TI - The movements of the components of the Hastings bipolar prosthesis. A radiographic study in 65 patients. AB - We aimed to find out whether the Hastings bipolar prosthesis moved in a bipolar fashion after its use for displaced fractures of the femoral neck. In 65 patients non-weight-bearing movement was assessed radiographically and compared with an earlier study of the Monk prosthesis. In 70% of patients, the only movement was between the acetabulum and the prosthetic shell, the prosthesis behaving as if it were unipolar. This did not change with time, but there was a slight improvement in the range of movement, particularly in flexion. The absence of movement between the outer shell and the metal head is most probably due to the design of the prosthesis and makes this prosthesis unsuitable for use in osteoarthritic hips. PMID- 2925731 TI - Deep vein thrombosis after total hip replacement. A comparison between spinal and general anaesthesia. AB - The effect of hypobaric spinal anaesthesia or narcotic-halothane-relaxant general anaesthesia on the incidence of postoperative deep vein thrombosis was studied in 140 elective total hip replacements in a prospective randomised manner. Deep vein thrombosis was diagnosed using impedance plethysmography and the 125I fibrinogen uptake test, combined, in selected cases, with ascending contrast venography. The overall incidence of deep vein thrombosis was 20%. Nine patients (13%) developed deep vein thrombosis in the spinal group and nineteen (27%) in the general anaesthetic group (p less than 0.05). The incidences of proximal thrombosis and of bilateral thrombi were also less with spinal anaesthesia than with general anaesthesia. It is concluded that spinal anaesthesia reduces the risks of postoperative thromboembolism in hip replacement surgery. The presence of varicose veins, being a non-smoker and having a low body mass index were associated with an increased incidence of deep vein thrombosis. PMID- 2925733 TI - Wear characteristics of the canine acetabulum against different femoral prostheses. AB - We studied cartilage degeneration in 45 canine acetabula after implantation of prostheses with articulating surfaces of low-temperature isotropic (LTI) pyrolytic carbon, cobalt-chromium-molybdenum alloy and titanium alloy for periods ranging from two weeks to 18 months. Gross specimens and histological sections were compared with the nonoperated (control) acetabulum of the same animal. Cartilage articulating with LTI pyrolytic carbon exhibited significantly lower levels of gross wear, fibrillation, eburnation, glycosaminoglycan loss, and subchondral bone change than with metallic surfaces. Survivorship analysis showed a 92% probability of survival for cartilage articulating with LTI pyrolytic carbon at 18 months, as compared to only a 20% probability of survival for cartilage articulating with either of the metallic alloys. PMID- 2925734 TI - Arthroscopic surgery for synovial chondromatosis of the hip. PMID- 2925735 TI - Intertrochanteric osteotomy for avascular necrosis of the femoral head. AB - Of 24 intertrochanteric osteotomies for avascular necrosis of the femoral head, 22 were followed up for an average of 63 months. Sixteen of the 22 cases had good or excellent results, including 5 of the 6 cases with Stage II disease and 11 of the 16 with Stage III changes. Success seemed to be inversely related to the size of the lesion. There were six major orthopaedic complications, but despite these we feel that the operation has a definite role in the treatment of the young active patient. PMID- 2925736 TI - Radiological loosening after cemented hip replacement for juvenile chronic arthritis. AB - We reviewed the results of 14 total hip replacements in patients with juvenile chronic arthritis. The mean age at operation was 16 years (range 12 to 22 years); follow-up was from four to 11 years (mean 8.5 years). Postoperatively pain relief was sustained in all but one hip, while movement generally remained significantly restricted. No hip has as yet required a revision operation, although eight hips (57%) show radiological changes suggestive of impending failure. All patients had severe polyarticular involvement with associated restriction of locomotor activity. Potential causes contributing to loosening such as continuing diaphyseal bone growth and increased immunocompetence in adolescence are discussed. PMID- 2925737 TI - The effect of hydroxyapatite coating on bone growth into porous titanium alloy implants. AB - In rabbits and goats, test implants with a porous surface of two layers of Tl-6A; 4V beads were examined at intervals for bond strength with bone. Half of the implants were coated with hydroxyapatite by plasma spray. The bonding strength with bone in the coated specimens was about four times greater than that of the uncoated specimens at two weeks, and twice as strong at six weeks. Twelve weeks after implantation, the strengths were similar. The hydroxyapatite coating of the beads provided earlier and stronger fixation. PMID- 2925738 TI - Some factors affecting the strength of the cement-metal interface. AB - A manufacturing technique to increase the bonding between bone cement and metal prostheses has been assessed in the laboratory by "push-out" tests, and the effects of contamination of the cement and of the prosthesis with blood and intramedullary contents have been studied. The technique, known as pre-coating, increases bond strength; this increase is preserved after contamination of the cement which does, however, cause some lowering of interface shear strength. The implications for clinical practice are discussed. PMID- 2925740 TI - Perthes' disease in yorkshire. AB - Perthes' disease is common in certain urban areas within Britain. It is one manifestation of a generalised growth disorder and nutritional causes are suspected. Orthopaedic surgeons throughout the Yorkshire region recorded all new patients with Perthes' disease over two years. There were large geographical differences in incidence which could not be explained by urban-rural or social class differences. No cases were recorded in a large area within the eastern part of the region, which is in high-grade farming land and has had a relatively low infant mortality throughout this century. PMID- 2925739 TI - Irritable hip and campylobacter infection. AB - Three cases are reported which presented as "irritable" or "observation" hips and failed to respond to rest at home and in hospital. In each case a campylobacter organism was grown from the faeces; none were found in a group of 20 patients in the paediatric ward for other reasons. The patients responded to a course of erythromycin. It is postulated that they may have had a reactive arthropathy of the hip and suggested that cultures for Campylobacter be made as part of the investigation of irritable hip. PMID- 2925741 TI - Operation for calcaneus deformity after surgery for club foot. AB - We describe three patients who developed gross calcaneus deformity following surgery for talipes equinovarus. One also had an associated valgus deformity and another had supination of the forefoot; all had intractable problems with footwear. Operation for transfer of the tibialis anterior to the heel, with correction of the associated deformities, was successful and improved both their gait and the shoe problems. PMID- 2925742 TI - Permanent anterior dislocation of the proximal tibiofibular joint. AB - We report two patients with permanent dislocation of the proximal tibiofibular joint and no history of trauma. Both needed operation, one for persistent pain and the other for common peroneal nerve involvement, and both had a good result. PMID- 2925743 TI - Tibial shortening for leg length discrepancy. AB - Over a 25-year period, 12 patients had from 2.5 to 5.1 cm operative shortening of the tibia and fibula for leg length discrepancy at between four and 18 years of age. All recovered normal function and there was minor cosmetic impairment in only two cases. The only vascular complication was temporary delay in return of the circulation to the foot after tourniquet removal in one patient. The procedure is valuable for discrepancy of tibial length in patients when they present too late for epiphyseal arrest, when there is doubt as to the appropriate timing for epiphyseal arrest, or when it is uncertain at an earlier stage whether there is need for surgical correction. PMID- 2925744 TI - Curve patterns in idiopathic scoliosis. A clinical and radiographic study. AB - We have developed a simple technique for demonstrating the sagittal profile of each rotated level of a scoliotic spine and used it to determine the patterns of lordosis and kyphosis in each of six clinical types of idiopathic scoliosis. The currently accepted classification of scoliosis is inaccurate and a modification is proposed. The three main types of scoliosis were shown to have sagittal profiles distinctly different from each other and from normal. Single structural curves had short lordotic sections at their apices, limited above and below by kyphosis. Double curves showed longer lordotic sections limited only by one area of kyphosis. Lordosis throughout the thoracic and lumbar spine was associated with triple curve patterns. The biomechanical effects of the abnormal sagittal profiles provide a simple explanation for the genesis and progression of the different types of scoliosis, and the recognition of the pattern of the sagittal abnormalities permits treatment to be designed on a sound anatomical basis for individual cases. PMID- 2925745 TI - Anterior spinal fusion for spondylolysis and isthmic spondylolisthesis. Long term results in adults. AB - We reviewed 20 adult patients with spondylolysis and isthmic spondylolisthesis an average of 10.5 years after treatment by anterior spinal fusion. Nineteen patients had excellent or satisfactory results. Ten of the patients were symptom free at one year, and 15 were asymptomatic at final follow-up. Anterior spinal fusion can produce results comparable to those of posterior fusion with or without decompression. The results tend to improve with time in contrast to the known worsening of late results after posterior decompression without fusion. PMID- 2925746 TI - Reduction and stabilisation of cervical dislocations. An analysis of 167 cases. AB - We compared retrospectively consecutive series of patients with cervical dislocation treated at two Australian centres. In Perth, 82 patients were treated by closed reduction and postural nursing. In Adelaide, 85 patients had closed reduction and early surgical stabilisation by interbody fusion. There were 46 bilateral dislocations, 101 unilateral dislocations, and 20 anterior subluxations. On admission 30 patients had complete tetraplegia, 17 incomplete tetraplegia, and 120 had minimal or no neurological loss. Our results indicated that closed manipulation under general anaesthesia is a safe and effective means of reduction in the acute stage. There was a high mortality rate for acute surgery in patients with complete tetraplegia. Early surgical stabilisation by dowel fusion reduced bed and hospital stay in patients with no neurological loss, but seemed to impair neurological recovery in patients with a neurological deficit on admission. Conservative management after reduction of bilateral dislocation or anterior subluxation led to a higher incidence of instability in patients with minimal or no neurological loss; in such cases surgery to stabilise the injured segment is indicated. PMID- 2925747 TI - Cranial symptoms after cervical injury. Aetiology and treatment of the Barre Lieou syndrome. AB - Neck injury of the whiplash type may lead to the cranial symptoms of the Barre Lieou syndrome. Forty patients with this syndrome and 40 without it were investigated by a variety of imaging techniques. There was a clear correlation between root sleeve defects at C3/4 shown by special oblique myelographic views and cranial symptoms. Good results were obtained by anterior cervical discectomy and fusion at C3/4 in 21 cases. It is suggested that the syndrome may result from irritation of the sympathetic nervous supply at this level. PMID- 2925748 TI - Does myeloma secrete an osteoblast inhibiting factor? AB - Unlike most other tumours, myeloma causes bone destruction without an osteoblastic reaction; we tried to assess whether myeloma secretes a humoral factor that inhibits osteoblasts. Human bone-derived cells were either co cultured with myeloma cells, or cultured in medium conditioned by myeloma cells. Bone-derived cell growth was measured by cell counts and by uptake of tritiated thymidine (3H-Tdr); growth was inhibited when cultured in medium conditioned by myeloma cells and some inhibition was seen when the bone-derived cells were co cultured with myeloma cells. The inhibiting effect was dose-dependent and also dependent upon the density of the myeloma cells conditioning the medium. The results of our study suggest that myeloma secretes an osteoblast inhibiting factor of less than 50,000 Dalton molecular weight. PMID- 2925749 TI - Traumatic hemipelvectomy. AB - Traumatic hemipelvectomy is rare, and is usually accompanied by injury to the genito-urinary tract and bowel. Recently, there have been an increasing number of reports of patients who have survived this injury, probably as a result of improved early care. We report three such cases and review the literature. The amputation wound should not be closed initially; early re-exploration to remove any dead tissue is indicated, and this should be repeated as necessary. PMID- 2925750 TI - Maximal isometric patellofemoral contact force in patients with anterior knee pain. AB - We assessed patellofemoral joint function by combining the measurement of maximal isometric extensor torque at the knee with clinical and radiological measurements in order to calculate the patellofemoral contact force. Eighteen volunteers established the normal ranges of results and the reliability of the system. Of the 39 patients with a variety of knee problems, 29 had anterior knee pain, and all had a subsequent arthroscopy. Patients with anterior knee pain and lesions in the patellar cartilage had significantly reduced isometric contact forces, but those with normal patellofemoral cartilage had normal contact forces. Our method may be useful in providing an objective assessment of anterior knee pain and a quantitative means of monitoring its treatment. PMID- 2925751 TI - Grading the outcome of pelvic fractures. AB - A system for assessment of function after major pelvic injuries is proposed. This numerical system developed from a five-year prospective study of 60 patients. Five factors were assessed and scored: pain, standing, sitting, sexual intercourse and work performance. The total score then gave a clinical grade as excellent, good, fair or poor. The scoring system allows comparison between early and late results and also between various methods of treatment. PMID- 2925753 TI - Cerclage for torsional fractures of the tibia. AB - We report the technique and results of percutaneous cerclage used in treating 186 torsional fractures of the tibia, most of which were due to skiing accidents in young patients. It is recommended only for this type of fracture and has the advantages of simplicity, a low rate of complications and a relatively brief period in hospital. PMID- 2925752 TI - Patterns of union in fractures of the waist of the scaphoid. AB - Eighty-two of 85 patients who had sustained a fracture of the waist of the scaphoid in 1985 were reviewed more than one year after injury. The incidence of nonunion, defined as a clear gap at the fracture site one year after injury, was 12.3%. This was much higher than expected. Most of the patients with nonunion had symptoms and had appreciable restriction of wrist movement. In a further 25% of the patients at review, the site of the fracture could be easily identified although it appeared to have healed. These patients were older and more of them were women. Three-quarters of these patients had symptoms but their wrist movement was essentially normal. PMID- 2925754 TI - Lethal air embolism during arthroscopy. A case report. AB - We report a case of lethal air embolism during diagnostic arthroscopy using air to distend an acutely injured knee. Air had escaped from the joint through an intra-articular fracture and entered the venous system. During arthroscopy, pressure within the joint may be 5 to 10 times higher than venous pressure, so any medium may escape. We advise that the use of air, especially in freshly injured joints, should be abandoned in favour of saline or carbon dioxide. PMID- 2925755 TI - Pseudomalignant heterotopic ossification ("myositis ossificans"). Recurrence after excision with subsequent resorption. AB - An eight-year-old boy presented with massive pseudomalignant heterotopic ossification around the upper femur. The mass was completely excised because of severe pain, systemic illness and a flexion contracture at the hip. Symptomatic improvement was swift, but two weeks later the mass had recurred and was even more extensive. During the subsequent 18 months of conservative management he has been free of pain and there has been progressive resorption and remodelling of the heterotopic bone. There is now no limitation of physical activity and movement at the hip is full. PMID- 2925756 TI - Knee stability after partial excision of tibial plateau: brief report. PMID- 2925757 TI - Epiphysiolysis of the great tuberosity of the calcaneum: brief report. PMID- 2925758 TI - Isolated calcaneo-cuboid dislocation: brief report. PMID- 2925759 TI - Sliding osteotomy for tailor's bunion: brief report. PMID- 2925760 TI - 60-year follow-up of talectomy for congenital talipes equinovarus: brief report. PMID- 2925761 TI - A new method of fixing radial neck fractures: brief report. PMID- 2925762 TI - The management of knee flexion contractures in haemophilia: brief report. PMID- 2925763 TI - Ectopia vesicae and congenital hip dislocation: brief report. PMID- 2925764 TI - Femoral neck arthroplasty after failed resurfacing: brief report. PMID- 2925766 TI - Axillary-subclavian venous thrombosis. AB - From 1974 through 1984 six patients with axillary-subclavian venous thrombosis were studied and treated. This disorder represents 1% of the various types of venous thrombosis reported in the literature. Symptoms appeared following effort in four patients, while a cervical rib and a scar bridle after radical mastectomy were identified as the underlying cause in two patients. Ages ranged from 17 to 59 years, with a mean age of 33 and equal sex distribution. None of the six patients had blood clotting defects. The diagnosis was based on clinical evaluation and was confirmed by phlebography. There was edema and functional impairment of the arm in all cases. Pain and venous prominence was found in 83%, rubor of the extremity in 66%, local hyperthermia in 50%, and arterial compression in 33%. Five patients were treated with anticoagulants and bed rest. Surgery was performed in two patients with thoracic outlet syndrome. First rib resection with scalenotomy was performed in one case and cervical rib resection with scalenotomy in the other. After a mean follow-up of 13 months, the results were good in four and average in two patients. PMID- 2925765 TI - Asymptomatic pulmonary embolism in patients with deep vein thrombosis. Is it useful to take a lung scan to rule out this condition? AB - One hundred and sixteen patients with proximal deep venous thrombosis (DVT) confirmed venographically had perfusion and ventilation lung scans performed 48 hours after admission to assess the incidence of asymptomatic pulmonary embolism (PE). Sixty-six patients had normal lung scans, 29 had high-probability defects suggestive of PE, and 21 had indeterminate-probability of PE. Chest X-ray, electrocardiogram and arterial blood gases were of no value in assessing the lung scan results. Six out of 29 patients with a baseline lung scan of high probability of PE experienced acute signs and/or symptoms suggestive of pulmonary embolism while on heparin therapy. A repeated scan this time did not disclose new perfusion defects in any patients. In the absence of a baseline study, these scans may be interpreted as demonstrating pulmonary embolism on treatment and lead to unnecessary caval interruption procedures for failed heparin therapy. PMID- 2925767 TI - Total anomalous pulmonary venous connection. Long-term results following repair under 3 months of age. AB - The surgical experience with total anomalous pulmonary venous connection (TAPVC) at the University of Louvain (Brussels) between the years 1975 and 1986 is reviewed. Nineteen patients aged two days to three months with TAPVC were studied. The types of TAPVC were supracardiac in 9 patients, cardiac in 4, infracardiac in 4 and mixed in 2. Profound hypothermia induced by surface cooling, limited cardiopulmonary by-pass and total circulatory arrest were used in all cases. The 4 early deaths concerned the first four neonates who were critically ill. All operative survivors are followed for a mean of 3.5 years (12 months to 8 years). There are two late deaths due to reoperation for pulmonary venous obstruction. All 13 survivors are well at last review. Eleven of them have been recatheterized 4 to 33 months after repair (19 months in average). The pulmonary artery and capillary pressures fell to a normal level after a few months. Ventricular function which was markedly depressed preoperatively, was evaluated by quantitative angiocardiography and echocardiography. It returned to normal late postoperatively. The hospital mortality for the repair of TAPVC in the neonates remains appreciable. Total correction at one operation is advisable. The incidence of postoperative pulmonary venous obstruction is of particular concern. The late postoperative functional and hemodynamic results are excellent. The repair of TAPVC can be considered curative. PMID- 2925768 TI - Treatment of major venous obstruction with an expandable endoluminal spiral prosthesis. AB - Six patients with extensive iliofemoral and/or caval thrombosis were treated by thrombectomy and subsequent implantation of an expandable endoluminal spiral prosthesis in case of congenital caval stenoses (1) or extravascular compression or traction (5). Five of these patients had undergone previous surgery and thrombosis had developed despite low dose heparin given postoperatively. Three patients had had an unsuccessful thrombectomy prior to spiral implantation. No complications related to the endoluminal prosthesis occurred. There was one retroperitoneal hematoma from guide wire perforation of the inferior vena cava (IVC) necessitating laparotomy and reversal of the previously constructed femoral av-fistula with subsequent iliofemoral rethrombosis. All other endoluminally reconstructed veins remained open at early and late (up to 12 months) review confirmed by phlebography. We conclude that with increasing clinical experience endoluminal relining of obstructed major veins will probably become a valuable method of venous reconstruction with minimal surgical trauma. PMID- 2925769 TI - Veno-venous bypass without systemic heparinization using a centrifugal pump: a blind comparison of a heparin bonded circuit versus a non heparin bonded circuit. AB - Veno-venous bypass without the use of systemic heparinization has recently become of increasing interest for application during liver transplantation and surgery on the large abdominal veins. However, possible adverse effects on blood components as demonstrated by means of hematologic and hemostatic parameters or on the occurrence of thromboembolic complications are until now not excluded. No consensus has been reached as to the efficacy of heparin coated circuits in those procedures. In the present study veno-venous bypass was performed for four hours in ten dogs using heparin coated and non coated circuits without further heparinization in a randomized blind fashion. No changes or significant intergroup differences were noted in the hematological and coagulation parameters. Macroscopic evaluation of the circuits revealed small strands of fibrin on all connector rims and clots in the center part of the pump head and at the cannula tips. The lungs showed two small emboli in large size pulmonary arteries and also two minor emboli in small size arteries. In four animals the emboli were equally divided between the two groups. As expected regarding the size of the clots no influences could be seen on hemodynamic or respiratory parameters. With Scanning Electronic Microscopy a monolayer of activated thrombocytes was observed on the surface of the bypass circuits in the coated as well as in the uncoated group. This study suggests that a veno-venous bypass without systemic heparinization is possible without serious damage to blood cellular elements or impressive activation of the coagulation system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2925771 TI - Intraoperative disruption of a Greenfield vena cava filter. AB - A case illustrating fracture and translocation of a Kim-Ray Greenfield filter strut due to intraoperative manipulation of the filter during cholecystectomy is presented. Awareness of this previously unreported complication is essential in preventing its occurrence. PMID- 2925770 TI - Implantable venous access device. AB - Procedures for long-term angio access have for many years made up a major component of vascular surgical practice. A totally implantable vascular device for chronic venous access developed in the early '80s compares favorably with other methods of angio access. We implanted 76 of these devices in 73 patients on the oncology service of Fairview General Hospital between May 1984 and May 1986. The infusion ports were in place for a total of 14,509 patient days with a 3.9% rate of catheter related sepsis and 6.5% rate of catheter occlusion. Three occlusions resolved with streptokinase. Pocket infection occurred as a late complication in 3 patients. Emphasis is placed on a modified technique for device implantation. Strict adherence to a simplified percutaneous technique for the silastic catheter placement via the subclavian vein, with creation of the reservoir pocket after adequate vascular access is secure, has led to no serious complications during placement. Routine use of fluoroscopy during this procedure helped avoid potential technical complications. The advantages and disadvantages of the implantable systems compared to the dacron cuffed silastic catheters are discussed. Patient acceptance is excellent and improved cost/benefit ratio has been observed when compared to other forms of chronic venous access. Implantable vascular devices can be safely inserted with little morbidity or risk to the patient. They provide a convenient route for drawing blood, administering chemotherapy, hyperalimentation, and intravenous therapy in oncology patients and may represent an advantage over Hickman-Broviac catheters and the attendant catheter related sepsis associated with their use. PMID- 2925772 TI - Giant arteriosclerotic aneurysm of the axillary artery. AB - A case of a rare giant arteriosclerotic aneurysm of the axillary artery is reported. Reconstruction was successfully performed with end-to-end anastomosis after resection of the aneurysm. The surgical technique is discussed. PMID- 2925773 TI - Emergency valve replacement for active infective endocarditis. AB - During the last 12 years, 14 patients were subjected to emergency heart valve replacement in acute bacterial endocarditis. Operative mortality was 21% (3/14); significant postoperative periprosthetic regurgitation or reinfection occurred in none of the survivors. Risk factors with unfavourable prognosis are: (1) virulent pathogens ("Non-Viridans"-germs); (2) previously normal heart valves; (3) acute aortic insufficiency with premature closure of the mitral valve; (4) floating vegetations shown by echocardiography. Our results provide further evidence for the efficacy of early surgical intervention in patients with bacterial endocarditis with an unfavourable etiology or a complicated course. PMID- 2925774 TI - Cardiac damage in nonpenetrating chest injuries. Report of 5 cases. AB - The Authors report 5 cases of cardiac injury after blunt chest trauma: (a) one right atrial disruption with acute tamponade treated successfully; (b) two left ventricular perforations with rib fractures: one patient was exsanguinated and died, the other one presented a late subacute cardiac tamponade with successful operative repair; (c) one isolated traumatic tricuspid insufficiency which was well tolerated; (d) one atrio-inferior caval disruption with acute tamponade. Cardiac damage secondary to nonpenetrating chest trauma is uncommon but with the present modes of high speed transportation they are occurring with increasing frequency; correct management of cardiac ruptures depends upon rapid recognition of the injury and expeditious surgical repair. The occurrence of tricuspid valvular lesions alone as a result of nonpenetrating trauma is not common. Echocardiographic examination after blunt chest trauma is a useful diagnosis procedure. PMID- 2925775 TI - Atrioventricular septal defect complicated by right ventricular outflow tract obstruction. Analysis of risk factors regarding surgical repair. AB - Eighteen patients with complete atrioventricular septal defect (AVSD) were found to have either associated tetralogy (n = 15) or pulmonary atresia (n = 3). Their pre- and post-operative course was reviewed focusing attention on risk factors for complete repair. These included right ventricular (RV) hypoplasia, identified by cineangiographic volume determinations in two cases (11%) and inadequate pulmonary artery size in one patient. In the 2 cases with RV hypoplasia and in one case, in whom all chordae of the AV valve were connected to a single right ventricular papillary muscle (AVSD type Rastelli B), complete repair was not feasible. In addition, angiography revealed coronary artery variations in 5/18 (28%), which did not preclude surgical repair. Palliative surgery was undertaken in 10 patients and complete repair carried out in five. Six of 18 patients died, 2 among those after complete repair. PMID- 2925776 TI - Effect of ultrafiltration on plasma colloid oncotic pressure and red cell volume during cardiopulmonary bypass. AB - Forty cardiopulmonary bypass patients were randomized into two matchable groups, an ultrafiltration and an control group. We have concluded that change of plasma colloid oncotic pressure may be a more sensitive parameter of monitoring the effect of ultrafiltration during cardiopulmonary bypass. PMID- 2925777 TI - Intra-operative echocardiography: a useful tool in the localization of small intracardiac foreign bodies. AB - Small intracardiac foreign bodies may be difficult to palpate and localize at surgery using conventional diagnostic procedures. The use of intra-operative echocardiography greatly facilitates the localization of intramyocardial foreign bodies, and minimizes operative time and iatrogenic myocardial damage. A case is presented in which this diagnostic modality was used. PMID- 2925778 TI - Successful resection of cardiac fibroma with ventricular tachycardia. AB - A 22-year-old male was admitted to Niigata University Hospital complaining of palpitation. Echocardiogram, cineangiogram, and Holter electrocardiogram revealed a cardiac fibroma complicated by ventricular tachycardia (VT). The tumor extended from the interventricular septum to the anterior surface of the left ventricle, and an electrophysiological study demonstrated that the focus of the VT was situated at the tumor. The tumor was excised successfully. The patient is doing well two years after operation without any antiarrhythmic drugs, and VT has not recurred. PMID- 2925779 TI - The fate of the freeze-preserved xenograft: an experimental study on rabbits, cats, and dogs. AB - Freeze-preserved allografts have been used successfully in patients for vascular peripheral replacement, dialysis, and chemotherapy. Freezing of veins seems to decrease or abolish antigenicity by decreasing the viable cellular components of the grafts. To confirm its acceptance and consequently, the high patency rates of freeze-preserved vein grafts, we inserted segments of human veins preserved at 80 degrees Centigrade as arterial substitutes into rabbits, cats, and dogs and studied the morphological changes of these xenografts up to 2 years. In all the groups, the patency rate was satisfactory. In rabbits and dogs, the cellular inflammatory reaction around the grafts and suture lines disappeared after a few weeks; the endothelium was reconstructed at 2 months and a poorly differentiated cellular fibro-collagenous wall with prominent hyalin matrix was observed. In cats, however, the histio-lymphocytic infiltrate persisted in functioning grafts up to 2 years associated with adjacent prominent vascular and nerve proliferation. It is suggested that this inflammatory reaction has no deleterious effect on the graft; on the contrary, it promotes its neovascularisation and innervation. The cat proved to be a good animal model for vascular surgical experiments. Our study proved the poor antigenicity of freeze-preserved venous xenograft. It could, in the future, be used for human arterial substitutes. PMID- 2925780 TI - Popliteal artery entrapment syndrome with distal embolization. A report of two cases. AB - The popliteal vascular entrapment syndrome has been recognized as a cause of arterial occlusion in young males for several decades. The ischemia is usually caused by thrombosis of the popliteal artery due to intimal trauma or aneurysm formation. Distal embolization to the tibial arteries and to the foot arch and digital vessels is common but is not emphasized in the literature. This distal embolization may precipitate severe ischemia which may preclude reconstruction or compromise the results of repair of the popliteal lesion. Early repair of the muscle anomaly is advocated even in the asymptomatic limb. Two patients with bilateral popliteal artery entrapment causing unilateral popliteal occlusion with distal embolization are reported. PMID- 2925781 TI - Intraoperative assessment of carotid endarterectomy. AB - In our experience intraoperative arteriography in carotid endarterectomy is very effective in detecting residual small lesions after surgery. There were no neurosurgical complications due to arteriography. The interpretation of the surgical results is objective since the criteria are the same as those used to assess preoperative arteriography. Different intraoperative assessment methods to control carotid endarterectomy are also analysed. PMID- 2925782 TI - Preservation of spinal cord function and prevention of paralysis during aortic occlusion via veno-arterial bypass. AB - Paraplegia secondary to spinal cord ischemia is a too frequent devastating complication of thoracic aneurysm surgery. We examined the ability of veno arterial bypass (VAB) to ensure adequate spinal cord blood flow during aortic cross-clamping by monitoring spinal cord function via somatosensory evoked potentials (SEP's) and postoperative motor function. Dogs were placed on VAB using a heparin-bonded roller pump circuit without systemic heparinization. SEP latency and amplitude were monitored continuously. The respirator FIO2 was set at 100% while the aorta was cross-clamped for one hour with the bypass adjusted to keep distal arterial pressure at greater than 60 mmHg. After one hour the aorta was unclamped, bypass discontinued, and the animals recovered. SEP's were always present during VAB as long as the distal pressure was kept at greater than 60 mmHg. There were several transient hypotensive episodes (less than 5 min) which were accompanied by reversible loss of SEP's. None of the animals displayed any gait abnormalities post-op. These findings using this simple bypass technique suggest the following conclusions: (1) SEP's degenerate (increased latency and decreased amplitude) in response to hypoxia; (2) spinal cord function can be maintained for up to one hour during hypoxic conditions; (3) SEP's can be used to monitor sensory spinal cord function under these conditions; and (4) heparinless VAB can provide spinal cord protection while also allowing monitoring of SEP's to ensure adequate spinal cord perfusion. PMID- 2925783 TI - Kinetochore structure: electron spectroscopic imaging of the kinetochore. AB - The structure of the kinetochore in thin section has been studied in the Indian muntjac by an electron spectroscopic imaging technique. This procedures allows the analysis of the distribution of phosphorus within the layers of the kinetochore. The results indicate that this element is a major component of both the inner and outer plates whereas it is largely absent in the middle plate and fibrous corona. The majority of the phosphorus is localized to a 30-nm fiber(s) that is woven through the layers of the kinetochore. The presence of phosphorus within this fiber, along with its morphological and biochemical features, indicates that it contains DNA. The fiber(s) occupies a major portion of the inner and outer plate where it forms a series of rows. It is rarely observed in the middle layer except where it passes between the inner and outer layers. The absence of structure in the middle plate suggests that it may represent a space rather than a plate that in turn may be related to the function of this region. The distribution of phosphorus within the kinetochore is neither altered by treatment with colcemid nor by the presence of microtubules at the kinetochore. Analysis of conventional micrographs of the kinetochore together with structural information obtained by electron spectroscopic imaging suggests that most microtubules insert and terminate between the rows of kinetochore fibers in the outer plate. However, some microtubules continue through the middle layer and terminate at the lower plate. The insertion of microtubules at different levels of the kinetochore may reflect the existence of functionally distinct microtubule classes. Electron spectroscopic imaging indicates that the microtubules associated with the kinetochore are phosphorylated. PMID- 2925784 TI - Induction and characterization of mitochondrial DNA mutants in Chlamydomonas reinhardtii. AB - In addition to lethal minute colony mutations which correspond to loss of mitochondrial DNA, acriflavin induces in Chlamydomonas reinhardtii a low percentage of cells that grow in the light but do not divide under heterotrophic conditions. Two such obligate photoautotrophic mutants were shown to lack the cyanide-sensitive cytochrome pathway of the respiration and to have a reduced cytochrome c oxidase activity. In crosses to wild type, the mutations are transmitted almost exclusively from the mating type minus parent. A same pattern of inheritance is seen for the mitochondrial DNA in crosses between the two interfertile species C. reinhardtii and Chlamydomonas smithii. Both mutants have a deletion in the region of the mitochondrial DNA containing the apocytochrome b gene and possibly the unidentified URFx gene. PMID- 2925785 TI - Reconstitution of the Golgi apparatus after microinjection of rat liver Golgi fragments into Xenopus oocytes. AB - We have studied the reconstitution of the Golgi apparatus in vivo using an heterologous membrane transplant system. Endogenous glycopeptides of rat hepatic Golgi fragments were radiolabeled in vitro with [3H]sialic acid using detergent free conditions. The Golgi fragments consisting of dispersed vesicles and tubules with intraluminal lipoprotein-like particles were then microinjected into Xenopus oocytes and their fate studied by light (LM) and electron microscope (EM) radioautography. 3 h after microinjection, radiolabel was observed by LM radioautography over yolk platelet-free cytoplasmic regions near the injection site. EM radioautography revealed label over Golgi stacked saccules containing the hepatic marker of intraluminal lipoprotein-like particles. At 14 h after injection, LM radioautographs revealed label in the superficial cortex of the oocytes between the yolk platelets and at the oocyte surface. EM radioautography identified the labeled structures as the stacked saccules of the Golgi apparatus, the oocyte cortical granules, and the plasmalemma, indicating that a proportion of microinjected material was transferred to the surface via the secretion pathway of the oocyte. The efficiency of transport was low, however, as biochemical studies failed to show extensive secretion of radiolabel into the extracellular medium by 14 h with approximately half the microinjected radiolabeled constituents degraded. Vinblastine (50 microM) administered to oocytes led to the formation of tubulin paracrystals. Although microinjected Golgi fragments were able to effect the formation of stacked saccules in vinblastine-treated oocytes, negligible transfer of heterologous material to the oocyte surface could be detected by radioautography. The data demonstrate that dispersed fragments of the rat liver Golgi complex (i.e., unstacked vesicles and tubules) reconstitute into stacked saccules when microinjected into Xenopus cytoplasm. After the formation of stacked saccules, reconstituted Golgi fragments transport constituents into a portion of the exocytic pathway of the host cell by a microtubule-regulated process. PMID- 2925786 TI - Acidification of endosome subpopulations in wild-type Chinese hamster ovary cells and temperature-sensitive acidification-defective mutants. AB - During endocytosis in Chinese hamster ovary (CHO) cells, Semliki Forest virus (SFV) passes through two distinct subpopulations of endosomes before reaching lysosomes. One subpopulation, defined by cell fractionation using free flow electrophoresis as "early endosomes," constitutes the major site of membrane and receptor recycling; while "late endosomes," an electrophoretically distinct endosome subpopulation, are involved in the delivery of endosomal content to lysosomes. In this paper, the pH-sensitive conformational changes of the SFV E1 spike glycoprotein were used to study the acidification of these defined endosome subpopulations in intact wild-type and acidification-defective CHO cells. Different virus strains were used to measure the kinetics at which internalized SFV was delivered to endosomes of pH less than or equal to 6.2 (the pH at which wild-type E1 becomes resistant to trypsin digestion) vs. endosomes of pH less than or equal to 5.3 (the threshold pH for E1 of the SFV mutant fus-1). By correlating the kinetics of acquisition of E1 trypsin resistance with the transfer of SFV among distinct endosome subpopulations defined by cell fractionation, we found that after a brief residence in vesicles of relatively neutral pH, internalized virus encountered pH less than or equal to 6.2 in early endosomes with a t1/2 of 5 min. Although a fraction of the virus reached a pH of less than or equal to 5.3 in early endosomes, most fus-1 SFV did not exhibit the acid-induced conformational change until arrival in late endosomes (t1/2 = 8-10 min). Thus, acidification of both endosome subpopulations was heterogeneous. However, passage of SFV through a less acidic early endosome subpopulation always preceded arrival in the more acidic late endosome subpopulation. In mutant CHO cells with temperature-sensitive defects in endosome acidification in vitro, acidification of both early and late endosomes was found to be impaired at the restrictive temperature (41 degrees C). The acidification defect was also found to be partially penetrant at the permissive temperature, resulting in the inability of any early endosomes in these cells to attain pH less than or equal to 5.3. In vitro studies of endosomes isolated from mutant cells suggested that the acidification defect is most likely in the proton pump itself. In one mutant, this defect resulted in increased sensitivity of the electrogenic H+ pump to fluctuations in the endosomal membrane potential. PMID- 2925787 TI - Endocytosis of the class I major histocompatibility antigen via a phorbol myristate acetate-inducible pathway is a cell-specific phenomenon and requires the cytoplasmic domain. AB - Class I major histocompatibility (MHC) antigens are expressed by virtually all mammalian cells, yet their levels of expression and behavior on the cell surface vary in a cell-specific fashion. A panel of lymphoid (both B and T) and nonlymphoid cell lines was used to study the kinetics of internalization of the H 2Ld class I MHC in different cell types. These studies revealed that endocytosis of H-2Ld occurs by both constitutive and PMA-regulated pathways in lymphoid cells, but only by a PMA-refractory pathway in the nonlymphoid cells tested. Transfectant derivatives of the T lymphoma, EL4, which express wild-type or mutant H-2Ld class I MHC antigens, were used to investigate the requirement for the cytoplasmic domain of the class I MHC antigen for its endocytosis in T lymphocytes. These studies showed that modification or deletion of the cytoplasmic domain of H-2Ld abrogates endocytosis via a PMA-regulated pathway. The role of cytoplasmic domain phosphorylation in PMA-inducible endocytosis was examined. The wild-type H-2Ld antigen is phosphorylated in all cell types examined, and this phosphorylation is up-regulated by PMA treatment. In contrast, cytoplasmic domain mutants of H-2Ld fail to be phosphorylated in vivo, in the presence or absence of PMA. The universality of PMA-inducible hyperphosphorylation of the class I MHC antigen among diverse cell types leads us to conclude that phosphorylation of the cytoplasmic domain, while perhaps necessary, is not sufficient for triggering endocytosis via a PMA-inducible pathway. Furthermore, the results with the cytoplasmic domain mutants of H-2Ld suggest that a structural conformation of the class I MHC cytoplasmic domain is required for endocytosis via this route. PMID- 2925788 TI - An enzyme trafficking defect in two patients with primary hyperoxaluria type 1: peroxisomal alanine/glyoxylate aminotransferase rerouted to mitochondria. AB - Most patients with the autosomal recessive disease primary hyperoxaluria type 1 (PH1) have a complete deficiency of alanine/glyoxylate aminotransferase (AGT) enzyme activity and immunoreactive protein. However a few possess significant residual activity and protein. In normal human liver, AGT is entirely peroxisomal, whereas it is entirely mitochondrial in carnivores, and both peroxisomal and mitochondrial in rodents. Using the techniques of isopycnic sucrose and Percoll density gradient centrifugation and quantitative protein A gold immunoelectron microscopy, we have found that in two PH1 patients, possessing 9 and 27% residual AGT activity, both the enzyme activity and immunoreactive protein were largely mitochondrial and not peroxisomal. In addition, these individuals were more severely affected than expected from the levels of their residual AGT activity. In these patients, the PH1 appears to be due, at least in part, to a unique trafficking defect, in which peroxisomal AGT is diverted to the mitochondria. To our knowledge, this is the first example of a genetic disease caused by such interorganellar rerouting. PMID- 2925789 TI - Subcellular localization of sterol carrier protein-2 in rat hepatocytes: its primary localization to peroxisomes. AB - Sterol carrier protein-2 (SCP-2) is a nonenzymatic protein of 13.5 kD which has been shown in in vitro experiments to be required for several stages in cholesterol utilization and biosynthesis. The subcellular localization of SCP-2 has not been definitively established. Using affinity-purified rabbit polyclonal antibodies against electrophoretically pure SCP-2 from rat liver, we demonstrate by immunoelectron microscopic labeling of ultrathin frozen sections of rat liver that the largest concentration of SCP-2 is inside peroxisomes. In addition the immunolabeling indicates that there are significant concentrations of SCP-2 inside mitochondria, and associated with the endoplasmic reticulum and the cytosol, but not inside the Golgi apparatus, lysosomes, or the nucleus. These results were confirmed by immunoblotting experiments with proteins from purified subcellular fractions of the rat liver cells carried out with the anti-SCP-2 antibodies. The large concentration of SCP-2 inside peroxisomes strongly supports the proposal that peroxisomes are critical sites of cholesterol utilization and biosynthesis. The presence of SCP-2 inside peroxisomes and mitochondria raises questions about the mechanisms involved in the differential targeting of SCP-2 to these organelles. PMID- 2925790 TI - Erythrocyte morphology reflects the transbilayer distribution of incorporated phospholipids. AB - The transbilayer distribution of exogenous phospholipids incorporated into human erythrocytes is monitored through cell morphology changes and by the extraction of incorporated 14C-labeled lipids. Dilauroylphosphatidylserine (DLPS) and dilauroylphosphatidylcholine (DLPC) transfer spontaneously from sonicated unilamellar vesicles to erythrocytes, inducing a discocyte-to-echinocyte shape change within 5 min. DLPC-induced echinocytes revert slowly (t1/2 approximately 8 h) to discocytes, but DLPS-treated cells revert rapidly (10-20 min) to discocytes and then become invaginate stomatocytes. The second phase of the phosphatidylserine (PS)-induced shape change, conversion of echinocytes to stomatocytes, can be inhibited by blocking cell protein sulfhydryl groups or by depleting intracellular ATP or magnesium (Daleke, D. L., and W. H. Huestis. 1985. Biochemistry. 24:5406-5416). These cell shape changes are consistent with incorporation of phosphatidylcholine (PC) and PS into the membrane outer monolayer followed by selective and energy-dependent translocation of PS to the membrane inner monolayer. This hypothesis is explored by correlating cell shape with the fraction of the exogenous lipid accessible to extraction into phospholipid vesicles. Upon exposure to recipient vesicles, DLPC-induced echinocytes revert to discoid forms within 5 min, concomitant with the removal of most (88%) of the radiolabeled lipid. On further incubation, 97% of the foreign PC transfers to recipient vesicles. Treatment of DLPS-induced stomatocytes with acceptor vesicles extracts foreign PS only partially (22%) and does not affect cell shape significantly. Cell treated with inhibitors of aminophospholipid translocation (sulfhydryl blockers or intracellular magnesium depletion) and then incubated with either DLPS or DLPC become echinocytic and do not revert to discocytic or stomatocytic shape for many hours. On treatment with recipient vesicles, these echinocytes revert to discocytes in both cases, with concomitant extraction of 88-99% of radiolabeled PC and 86-97% of radiolabeled PS. The accessibility of exogenous lipids to extraction is uniformly consistent with the transbilayer lipid distribution inferred from cell shape changes, indicating that red cell morphology is an accurate and sensitive reporter of the transbilayer partitioning of incorporated exogenous phospholipids. PMID- 2925791 TI - Microtubule polarities indicate that nucleation and capture of microtubules occurs at cell surfaces in Drosophila. AB - Hook decoration with pig brain tubulin was used to assess the polarity of microtubules which mainly have 15 protofilaments in the transcellular bundles of late pupal Drosophila wing epidermal cells. The microtubules make end-on contact with cell surfaces. Most microtubules in each bundle exhibited a uniform polarity. They were oriented with their minus ends associated with their hemidesmosomal anchorage points at the apical cuticle-secreting surfaces of the cells. Plus ends were directed towards, and were sometimes connected to, basal attachment desmosomes at the opposite ends of the cells. The orientation of microtubules at cell apices, with minus ends directed towards the cell surface, is opposite to the polarity anticipated for microtubules which have elongated centrifugally from centrosomes. It is consistent, however, with evidence that microtubule assembly is nucleated by plasma membrane-associated sites at the apical surfaces of the cells (Mogensen, M. M., and J. B. Tucker. 1987. J. Cell Sci. 88:95-107) after these cells have lost their centriole-containing, centrosomal, microtubule-organizing centers (Tucker, J. B., M. J. Milner, D. A. Currie, J. W. Muir, D. A. Forrest, and M.-J. Spencer. 1986. Eur. J. Cell Biol. 41:279-289). Our findings indicate that the plus ends of many of these apically nucleated microtubules are captured by the basal desmosomes. Hence, the situation may be analogous to the polar-nucleation/chromosomal-capture scheme for kinetochore microtubule assembly in mitotic and meiotic spindles. The cell surface-associated nucleation-elongation-capture mechanism proposed here may also apply during assembly of transcellular microtubule arrays in certain other animal tissue cell types. PMID- 2925793 TI - Experimental observations on the development of polarity by hippocampal neurons in culture. AB - In culture, hippocampal neurons develop a polarized form, with a single axon and several dendrites. Transecting the axons of hippocampal neurons early in development can cause an alteration of polarity; a process that would have become a dendrite instead becomes the axon (Dotti, C. G., and G. A. Banker. 1987. Nature (Lond.). 330:254-256). To investigate this phenomenon more systematically, we transected axons at varying lengths. The greater the distance of the transection from the soma, the greater the probability for regrowth of the original axon. However, it was not the absolute length of the axonal stump that determined the response to transection, but rather its length relative to the lengths of the cell's other processes. If one process was greater than 10 microns longer than the others, it invariably became the axon regardless of its identity before transection. Conversely, when a cell's processes were nearly equal in length, it was impossible to predict which would become the axon. In these cases, axonal outgrowth began only after a long latency. During this interval, the processes appeared to be in dynamic equilibrium, some growing for short distances while others retracted. When one process exceeded the others by a critical length, it rapidly elongated to become the axon. The establishment of neuronal polarity during normal development may similarly involve an interaction among processes whose identities have not yet been determined. When, by chance, one exceeds the others by a critical length, it becomes specified as the axon. PMID- 2925792 TI - Assembly and exchange of intermediate filament proteins of neurons: neurofilaments are dynamic structures. AB - We have explored the dynamics of intermediate filament assembly and subunit exchange using fluorescently labeled neurofilament proteins and a fluorescence resonance energy transfer assay. Neurofilaments (NFs) are assembled from three highly phosphorylated proteins with molecular masses of 180 (NF-H), 130 (NF-M), and 66 kD (NF-L) of which NF-L forms the structural core. The core component, NF L, was stoichiometrically labeled at cysteine 321 with fluorescein, coumarin, or biotin-maleimide to produce assembly-competent fluorescent or biotinylated derivatives, respectively. Using coumarin-labeled NF-L as fluorescence donor and fluorescein-labeled NF-L as the fluorescence acceptor, assembly of NF filaments was induced by rapidly raising the NaCl concentration to 170 mM, and the kinetics was followed by the decrease in the donor fluorescence. Assembly of NF-L subunits into filaments does not require nucleotide binding or hydrolysis but is strongly dependent on ionic strength, pH, and temperature. The critical concentration of NF-L, that concentration that remains unassembled at equilibrium with fully formed filaments, is 38 micrograms/ml or 0.6 microM. Under physiological salt conditions NF-L filaments also undergo extensive subunit exchange. Kinetic analysis and evaluation of several possible mechanisms indicate that subunit exchange is preceded by dissociation of subunits from the filament and generation of a kinetically active pool of soluble subunits. Given the concentration of NF-L found in nerve cells and the possibility of regulating this pool, these results provide the first information that intermediate filaments are dynamic structures and that NF-L within the NF complex is in dynamic equilibrium with a small but kinetically active pool of unassembled NF-L units. PMID- 2925794 TI - Skeletal muscle denervation activates acetylcholine receptor genes. AB - Transcriptional activity of acetylcholine receptor subunit genes was investigated in innervated and denervated chick skeletal muscle. The sciatic nerve of 3-d-old White Leghorn chicks was sectioned unilaterally; after various intervals, nuclei were isolated from operated and sham-operated animals, and run-on assays performed. Nuclei were incubated with 32P-UTP, and total RNA was extracted and hybridized onto filters containing an excess of subunit-specific DNA. Specific transcripts were detected by autoradiography and quantitated densitometrically. A sharp increase in transcriptional activity was observed to begin approximately 1/2 d after the operation and peak 1 d later when transcriptional rates reached approximately seven-, six-, and fivefold control levels for the alpha-, delta-, and gamma-subunit genes, respectively. The specificity of the effect was ascertained by normalization to total RNA synthesis and by the demonstration that several nonreceptor genes respond differently to denervation. These results suggest that a denervation signal reaches the genome to induce receptor expression. In addition, since the increase in mRNA levels significantly exceeds what can be accounted for by increased gene activity, posttranscriptional effects are suggested. PMID- 2925795 TI - Involvement of rRNA synthesis in the enhanced survival and recovery of protein synthesis seen in thermotolerance. AB - Although acquired thermotolerance has been linked to the induction of heat shock proteins, the molecular mechanism(s) by which cells become resistant to heat is unknown. The present study shows a strong correlation between the survival of cells following heat shock and the rate of recovery of protein, total RNA, and rRNA synthesis. Increasing exposure of CHO cells to 45 degrees C was found to decrease survival and cause a lengthening delay in these synthetic processes. The same reciprocal correlation was seen in thermotolerant cells. As thermotolerance develops, more cells survive a heat challenge and the delay in synthesis decreases. These data argue that enhanced recovery of protein and RNA synthesis is one factor which plays a key role in thermotolerance. The involvement of rRNA synthesis was further investigated by using actinomycin D at 0.1 microgram m1( 1), a concentration at which rRNA synthesis is selectively inhibited. When the drug was present during the recovery from a challenge heat treatment, the survival of thermotolerant cells was approximately 3-fold lower than expected from the mild toxicity of the drug. As this could not be accounted for by an interaction of the drug with the response of cells to single heat treatments, it is concluded that the drug inhibits the expression of thermotolerance in cells which would otherwise express a full degree of thermotolerance. The time and concentration dependence of this effect indicates that the drug acts though inhibition of rRNA synthesis. Therefore, enhanced recovery of RNA synthesis, presumably rRNA synthesis, is identified as one of the mechanisms responsible for enhanced survival of thermotolerant cells following heat shock. PMID- 2925796 TI - Effects of N,N-dimethylformamide and extracellular matrix on transforming growth factor-beta binding to a human colon carcinoma cell line. AB - Alterations in the binding of transforming growth factor-beta (TGF-beta) to the MOSER human colon carcinoma cell line caused by N,N-dimethylformamide (DMF) or extracellular matrix (ECM) were examined. DMF induced a more differentiated phenotype in the MOSER cells and resulted in a twofold increase in TGF-beta binding to the cells. This was due to an increase in receptor number with no significant alteration in the KD. The extent of increased TGF-beta binding was dependent on the dose and time of exposure to DMF. Upon removal of DMF, the receptor level returned to that of untreated cells within 6 hr. The binding of TGF-beta 1 and TGF-beta 2 to the cells was increased equally. Despite this increase in TGF-beta binding in the presence of DMF, the sensitivity of the MOSER cells to the growth inhibitory effects of TGF-beta was unaltered. Growth of the MOSER cells on ECM derived from a well-differentiated colon cell line increased the TGF-beta receptor number twofold without altering the KD. No change was observed if the MOSER cells were grown on ECM derived from a poorly differentiated cell line. While no alteration in sensitivity to TGF-beta was observed on cells grown in the presence of DMF, MOSER cells grown on the ECM derived from well-differentiated colon carcinoma cell lines were twofold more sensitive to the growth inhibitory effects of TGF-beta. These results indicated that growth conditions which resulted in a more differentiated phenotype resulted in an increase in the cellular receptors for TGF-beta. PMID- 2925797 TI - Effect of 5-amino-4-imidazolecarboxamide riboside (AICA-riboside) on the purine nucleotide synthesis and growth of rat kidney cells in culture: study with [15N]aspartate. AB - The present investigation evaluates the effect of AICA-Riboside on the synthesis of purine nucleotides and the growth of normal rat kidney cells in culture. Experiments in the presence and absence of various concentrations of AICA Riboside were conducted with Dulbecco's Modified Eagle's Medium supplemented with either 1 mM [15N]aspartate or [14N]aspartate. Addition of 50 microM AICA-Riboside to the incubation medium significantly stimulated intracellular adenine nucleotide concentrations following incubation for 48 hours. This stimulation was associated with augmented cell growth and DNA concentration. In contrast, with concentrations above 100 microM of AICA-Riboside in the incubation medium, there was a remarkable inhibition of cell growth and a significant depletion of intracellular pools of adenine nucleotides and DNA. Experiments with [15N]aspartate showed that the initial rate (0-24 hours) of [6-15NH2]adenine nucleotide formation from 1 mM [15N]aspartate was 38.8 +/- 9.6, 67.9 +/- 12.5, and 20.1 +/- 3.8 pmol h-1/10(6) cells in the presence of 0 (control), 50 microM and 500 microM AICA-Riboside, respectively. These observations indicate that the main effect of AICA-Riboside is on the formation of AMP from aspartate and IMP via the sequential action of adenylosuccinate synthetase and adenylosuccinate lyase. The current studies suggest that AICA-Riboside could be used as a factor mediating renal cell mitosis in culture. AICA-Riboside has a biphasic effect on the growth of renal epithelial cells in culture and on their intracellular purine nucleotides and DNA concentration. PMID- 2925798 TI - Ultraviolet light-induced inhibition of small nuclear RNA synthesis. AB - Two apparently distinct types of inhibition of the synthesis of U1, U2, U3, U4, and U5 small nuclear RNA, induced by ultraviolet (UV) radiation, have been described before: immediate and delayed. Our present observation can be summarized as follows: a) neither the immediate nor the delayed inhibition appear to be mediated by the formation of cyclobutane pyrimidine dimers, since they were not prevented by photoreactivating light, in ICR 2A frog cells; b) the inhibition of U1 RNA synthesis, monitored in HeLA cells within the first few minutes after irradiation, extrapolated to a substantial suppression at time zero of postirradiation cell incubation, providing further support for the proposal that the immediate inhibition is a reaction separate from the delayed UV light-induced inhibition of U1 RNA synthesis; c) the transition from the pattern of the immediate inhibition to that of the delayed inhibition (disappearance of the UV resistant fraction of U1 RNA synthesis and increased rate of inhibition) occurred gradually, without an apparent threshold, within the first 2 hr of incubation after irradiation; and d) the incident UV dose that resulted in a 37% level of residual U1 RNA synthesis (D37) during the delayed inhibition was about 7 J/m2, with an apparent UV dose threshold, and was about 60 J/m2 for the immediate inhibition. PMID- 2925799 TI - Effects of 1,25-dihydroxyvitamin D3 on cell-cycle kinetics of T 47D human breast cancer cells. AB - The replication of several human and animal cancer cell lines is regulated in vitro and in vivo by 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], the hormonally active form of vitamin D3. We have examined the effects of concentrations of 1,25 (OH)2D3, which inhibit cellular replication, on the cell-cycle kinetics of a 1,25 (OH)2D3-responsive human breast cancer cell line, T 47D. After 6 or 7 days of treatment, a time period representing approximately five cell population doublings of control cultures, concentrations of 1,25-(OH)2D3 in the range 10(-9) M to 10(-6) M caused a time- and concentration-dependent decrease in cell numbers. Treatment of cells growing in charcoal-treated fetal calf serum with 10( 8) M 1,25-(OH)2D3 for 6 days reduced cell numbers to 49% +/- 9% (n = 9) of control, and this was associated with a marked increase in the proportion of cells in the G2 + M phase of the cell cycle from 9.7% +/- 0.5% (n = 11) to 19.6% +/- 2.3% (n = 9), significant by paired analysis (P less than 0.002). At higher concentrations of 1,25-(OH)2D3 (10(-7)-10(-6) M), there was a concentration dependent decline in S phase and increases in both G0/G1 and G2 + M phase cells. Detailed analysis of the temporal changes in cell-cycle phase distribution following treatment with 2.5 X 10(-8) and 10(-7) M 1,25-(OH)2D3 showed an initial accumulation of cells in G0/G1 and depletion of S phase cells during the first 24 hr of treatment. This decline in S phase cells was not accompanied by a decline in % G2 + M indicating a transition delay in G2 or mitosis. At the lower dose these changes returned to control values at 48 hr and at later times were associated with a slight but consistent decline in G0/G1 phase and an increase in G2 + M. In contrast cells treated with 10(-7) M 1,25-(OH)2D3 had significantly elevated % G0/G1 cells at days 2 and 3, consistent with a transition delay through G1 phase. This was confirmed in stathmokinetic experiments which demonstrated an approximate sevenfold decrease in the rate of exit of cells from G0/G1 following 4 days of exposure to 10(-7) M 1,25-(OH)2D3. This accumulation of cells in G0/G1 was accompanied by a fall in % S phase cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2925800 TI - [Treatment of lithiasis of the common bile duct]. AB - The aim of this review is to explain the multidisciplinary conception of the treatment of stones of the common bile duct in terms of the various techniques available. Treatment is designed to decrease mortality and morbidity, particularly acute complications in elderly or high risk subjects. A rational tactic determined dispassionately by common sense constitutes the best chance of preventing complications. PMID- 2925801 TI - [Technic of tissue expansion]. AB - The technique of tissue expansion is rapidly developing. It resolves certain problems encountered in plastic and reconstructive surgery, in the scalp, for example, which constitutes an ideal indication. A correct strategy and technique, together with well defined indications allows a very significant reduction in the complication rate. The choice of prosthesis and its location also play an important role. There are many indications in the scalp, but tissue expansion may also be useful in Poland's syndrome, in giant naevi in children and for expansion of certain flaps. Rapid intra-operative expansion also appears to be a promising technique. PMID- 2925802 TI - [Technics of extensive lymph node curettage in cancer of the esophagus]. AB - During esophagectomy for cancer traditional lymph node curettage is performed extensively in the lower region but is practically nonexistent towards the upper zone, which fails to correspond to a satisfactory anatomic and oncologic exeresis. An operative technique has been adopted to extend lymph gland curettage, particularly in the anterior and superior mediastinum in the region of the recurrent and cervical chains. An analysis is performed of the advantages (increased survival) and inconveniences (increased postoperative morbidity) inherent in these extensive lymph node curettages. PMID- 2925803 TI - [Anatomical basis of the transposition of the serratus anterior muscle. Study of 40 dissections]. AB - In order to explore the possibility of serratus anterior muscle (SAM) flap transposition in head-neck and thoracic surgery, we performed an anatomical study including 40 dissections of the muscle's vascular pedicle, the subscapular thoracodorsal axis, which is a branch of the axillary artery (A. subscapularis A. thoracodorsalis). The SAM is characterized by: its location: extending from the anterior and lateral aspect of the thorax to the medial border of the scapula; its easy surgical access; its constant and reliable vascularization by the thoracodorsal artery, a branch of the subscapular artery; its long arc of rotation allowing the utilization of the SAM flap in head and neck and mediastinal surgery without microvascular anastomoses; its versatility in comparison with other perithoracic muscles. These considerations prompted us to use the SAM in head and neck reconstructive surgery, chest wall surgery, chest wall reconstruction following resection for tumor; breast reconstruction; intrathoracic and mediastinal surgery, reinforcement of high-risk tracheobronchial sutures or anastomoses; management of bronchopleural fistulas and empyema spaces; repair of tracheo esophageal fistulas and tracheal or esophageal defects. PMID- 2925804 TI - [Treatment of morbid obesity by gastric bypass. Apropos of 1158 cases treated surgically]. AB - After defining pathological obesity and describing the technical methods used for gastric bypass, a series of 1158 surgical cases is analysed. Discussion, supported by a review of the literature, involved post-operative mortality and morbidity, mid-term results and patient selection criteria. In the light of the results obtained, it would no longer appear justified to offer this type of surgical procedure. PMID- 2925805 TI - [Stress urinary incontinence associated with an ectopic ureteral junction. Apropos of 1 case]. PMID- 2925806 TI - A crosslinguistic investigation of vowel formants in babbling. AB - A cross-cultural investigation of the influence of target-language in babbling was carried out. 1047 vowels produced by twenty 10-month-old infants from Parisian French, London English, Hong Kong Cantonese and Algiers Arabic language backgrounds were recorded in the cities of origin and spectrally analysed. F1-F2 plots of these vowels were obtained for each subject and each language group. Statistical analyses provide evidence of differences between infants across language backgrounds. These differences parallel those found in adult speech in the corresponding languages. Implications of an early build-up of target-language oriented production skills are discussed. PMID- 2925807 TI - Acquisition of complementation. AB - This study concerns the acquisition of complex sentences with perception and epistemic verbs that take a second verb in their complements. The acquisition of complementation began between two and three years of age in this longitudinal study of four children's spontaneous speech. The results of the study showed that (1) complement types and complementizer connectives and (2) the discourse contexts in which complementation occurred were specific to individual matrix verbs. The most frequent verbs acquired were the perception verbs see and look and the epistemic verbs think and know. Developments in both discourse and syntax indicated that these verbs expressed attitudes of certainty/uncertainty toward the content expressed in their complements. The results are discussed in terms of both linguistic and psychological factors in the acquisition of complex sentences with complementation. PMID- 2925808 TI - Induction and the acquisition of English auxiliaries: the effects of differentially enriched input. AB - Children aged 2;0 to 2;6 participated in a longitudinal study examining their acquisition of the English auxiliary system following a six-week period in which they were exposed to additional auxiliary input in varying sentence contexts. Groups of children received enrichment utterances with the auxiliary could either in first position in the sentence, in middle position, or in both positions. Children in the front position group were significantly advanced over the other experimental groups in acquiring modal auxiliaries but not non-modals. However, none of the experimental groups differed significantly from a baseline group which received no additional could input. The implications of these findings for understanding the mechanisms of auxiliary acquisition and the nature of children's grammatical categories are discussed. PMID- 2925809 TI - Alternative explanations for the relationship between maternal verbal interaction style and child language development. AB - The present study analysed formerly unexamined indirect routes for relationships between time 1 maternal speech and later child language development. Ten normally developing children in Brown's early stage 1 and their mothers were the subjects. For each dyad, two free-play sessions occurring five months apart were videotaped in the subjects' homes. Mothers' pragmatic language use was coded from time 1 sessions. Child language level was coded at both sessions. Even though time 1 scores of the outcome were controlled, seven of the ten relationships involving mother speech and child language development were indirectly related through one of two time 1 child language measures. The results indicate that a mother-driven, direct influence model may be inappropriate for many mother speech-child language development relationships. We argue that child-driven and mother-driven explanatory models for the indirect relationships are equally feasible. PMID- 2925810 TI - Rhyme and alliteration in poems elicited from young children. AB - Attempts were made to elicit poems from 133 children between the ages of 2 and 6. Seventy-eight of the children produced 606 poems between them. Sixty per cent of the poems contained phonological devices; 42% contained rhyme and 26% contained alliteration. There was no obvious age trend as regards the use of rhyme but the frequency of alliteration declined with age. There were no significant age differences as regards the relative frequency with which different phonemes were manipulated in rhyme and alliteration. The possible functions of such sound-based language play in language development are discussed, with special reference both to children's sound play in crib speech, and to the development of phonological awareness and its importance in learning to read. PMID- 2925811 TI - Phonetic development in early infancy: a study of four Swedish children during the first eighteen months of life. AB - The present paper presents data on the phonetic development of four normal Swedish infants, who were audiorecorded bi-weekly in their homes from 0;1 to 1;5. Our results show five distinct stages in the development of early vocalizations: the glottal stage, the velar/uvular stage, the vocalic stage, the reduplicated consonant babbling stage and the variegated consonant babbling stage. The results are based on auditory analysis of selected parts of the material. A comparison is made of this developmental pattern with studies of infants raised in other linguistic communities. The results of this comparison support the claim that babbling follows a universal developmental pattern. PMID- 2925812 TI - Children's over-regularization of nouns and verbs. AB - The procedure used by Pratt, Tunmer & Bowey (1984) was employed in this study to investigate young children's abilities to correct over-regularized plural nouns and verbs in the past tense. Older children (mean age 6;4) performed better than younger children (mean age 4;11) and plural nouns were corrected significantly more than past-tense verb forms. As predicted, the younger children were better at correcting the nouns than the verbs; the two grammatical forms were corrected equally well by the older children. PMID- 2925813 TI - On the developmental contour of child language: a reply to Smith & Weist. AB - A developmental perspective in child language research begins with a focus on the child and the processes that contribute to change in the child's knowledge of language. Developmental change occurs in an organized, systematic way, with later changes influenced at least in part by developments at an earlier time. The acquisition of tense and aspect provides a relevant example. Data previously published by Weist, Wysocka, Witkowska-Stadnik, Buczowska & Konieczna (1984) are reanalysed here to show, statistically, that children learning Polish are influenced by aspect in acquiring verb tense, just as children are in learning English, Italian, Hebrew, Turkish and other languages. Children beginning to learn verb infections find aspectual contour particularly compelling in leading them to learn tense distinctions. PMID- 2925814 TI - Crossing boundaries: more evidence for phonological constraints on early multi word utterances. AB - A number of researchers have argued that phonological constraints may influence the emergence and form of combinatorial speech in children. Donahue (1986) presented evidence that one child's consonant harmony constraint operated across word boundaries. This paper presents further evidence for the operation of word level phonological constraints in multi-word utterances. Selection and avoidance patterns as well as her modifications of adult forms indicate the presence of a syllable sequencing constraint in this child's grammar: an initial syllable must begin with a consonant whose sonority value is not less than that of the following syllable. The same constraint governs the form of her early word combinations. The existence of evidence for the operation of word-level constraints in word combinations, it is pointed out, has consequences for how we interpret two-lexicon models of phonological development. PMID- 2925815 TI - How the prosodic cues in motherese might assist language learning. AB - The function of motherese has become a pivotal issue in the language-learning literature. The current research takes the approach of asking whether the prosodic characteristics that are distinctive to motherese could play a special role in facilitating the acquisition of syntax. Hirsh-Pasek, Kemler Nelson, Jusczyk, Cassidy, Druss & Kennedy (1987) showed that infants aged 0;7-0;10 are sensitive to prosodic cues that would help them segment the speech stream into perceptual units that correspond to clauses. The present study shows that infants' sensitivity to segment-marking cues in ongoing speech holds for motherese but not for adult-directed speech. The finding is that, for motherese only, infants orient longer to speech that has been interrupted at clausal boundaries than to matched speech that has been interrupted at within-clause locations. This selective preference indicates that the prosodic qualities of motherese provide infants with cues to units of speech that correspond to grammatical units of language-a potentially fundamental contribution of motherese to the learning of syntax. PMID- 2925816 TI - The systematic acquisition of word forms by a child during the first-fifty-word stage. AB - This paper sets out to examine two findings reported in the literature: one, that during the one-word stage a child's word productions are highly phonetically variable, and two, that the one-word stage is qualitatively distinct from subsequent phonological development. The complete set of word forms produced by a child at the one-word stage were collected and analysed both cross-sectionally (month by month) and longitudinally (looking for changes over time). It was found that the data showed very little variability, and that phonological development during the period studied was qualitatively continuous with subsequent development. It is suggested that the phonologically principled development of this child's first words is related to his late onset of speech. PMID- 2925817 TI - A multiple form word production checklist for assessing early language. AB - We describe the development of a set of five equivalent checklists to assess word production of children in their second year. The words on each list do not overlap, but represent comparable levels of difficulty. Thus, individual lists may be used to estimate the child's production vocabulary, and the set of lists may be used serially in a longitudinal design. A validation study on 25 infants suggests that the five lists produce comparable mean production scores, reflect differences in age, and preserve individual differences in total production and production of linguistic categories such as nouns, verbs, open class items, and closed class items. This finding provides further support for the reliability of parental report instruments in this developmental domain. PMID- 2925818 TI - Agreement between parents' and teachers' ratings of behavioral/emotional problems of children aged 4-12. AB - Parents' and teachers' reports of behavioral/emotional problems in 1161 children aged 4-12 from the general population and assessed via the Achenbach Child Behavior Checklist were compared. Low to moderate agreement was found, with parents reporting more problems than teachers. Agreement was higher for externalizing problems than for internalizing problems and higher for children receiving special education than for those receiving regular education. Agreement was slightly higher for older than younger children. Sex of the child did not influence parent-teacher agreement. Teachers scored children higher on problems related to peer relations and on problems interfering with academic functioning, whereas parents scored their children higher on problems associated more strongly with externalizing than with internalizing syndromes. PMID- 2925819 TI - Child behavior ratings: the influence of maternal characteristics and child temperament. AB - This study investigated the extent to which maternal characteristics, such as psychological health problems, marital adjustment and confidence in mother/wife roles, influenced how mothers rated the behavior of their first-born children (n = 100) on the Pre-school Behavior Questionnaire. Results showed that these characteristics were powerful predictors of behavior ratings. In contrast, the independent contribution of child temperament ratings was relatively small. It was concluded that child behavior problem and temperament measures may be confounded. Maternal ratings constitute a valuable source of information concerning parent-child interaction which deserve further investigation, especially of their influence on generally accepted measures of child behavioral adjustment. PMID- 2925820 TI - Subtypes of suicidal and assaultive behaviors in adolescent psychiatric inpatients: a research note. AB - Among 129 adolescent psychiatric inpatients, four subgroups of suicidal and/or assaultive behaviors were identified. A suicidal-only subgroup with no evidence of assaultive behavior was characterized by depression, drug abuse and environmental stresses. An assaultive-only subgroup with no evidence of suicidal behavior exhibited aggressive symptoms and violence at home. A subgroup with both suicidal and assaultive behaviors experienced accidents and family violence. A fourth subgroup had neither suicidal nor assaultive behavior. This subgroup showed eating disorders, depression, minimal assaultiveness and few peer friendships. PMID- 2925821 TI - IQ and behavioural adjustment of ex-institutional adolescents. AB - A group of children raised in institutions until at least 2 years of age, then adopted or restored to a biological parent, have been followed longitudinally into mid-adolescence. No effect of early institutionalisation was found on IQ which depended largely on the type of family placement. Behavioural and emotional difficulties were more common in the ex-institutional group than in a matched comparison group, according to teacher questionnaires and interviews with the adolescents and their parents. The findings are discussed in relation to placement policy and the question of the long-term effects of early experience. PMID- 2925822 TI - Social and family relationships of ex-institutional adolescents. AB - The adolescents described in the preceding companion article (J. Child Psychol. Psychiat. 30, 53-75, 1989) had experienced multiple changing caregivers until at least 2 years old. Such maternal deprivation did not necessarily prevent them forming strong and lasting attachments to parents once placed in families, but whether such attachments developed depended on the family environment, being much more common in adopted children than in those restored to a biological parent. Both these groups alike, however, were more oriented towards adult attention, and had more difficulties with peers and fewer close relationships than matched comparison adolescents, indicating some long term effects of their early institutional experience. PMID- 2925823 TI - Memory impairments and communication in relatively able autistic children. AB - Autistic people have specific memory difficulties. The effects of these difficulties on communication in relatively able autistic children and learning impaired controls were assessed in three experiments. The experiments tested the ability to: (1) carry out instructions; (2) ask questions without repetition; and (3) answer questions about past activities. When specific memory skills were required autistic children's communication was impaired relative to controls. When the need to use these skills was eliminated from the tasks the autistic children performed as well as controls. Some practical and theoretical implications of the findings are discussed. PMID- 2925824 TI - Determination of acetaminophen in human plasma by ion-pair reversed-phase high performance liquid chromatography. Application to a single-dose pharmacokinetic study. AB - The determination of acetaminophen in biological samples of humans who have ingested normal and overdosage of the drug is necessary to understand the clinical pharmacokinetics of acetaminophen and to determine its distribution and toxicokinetic parameters. This paper describes a rapid, simple, and sensitive high-performance liquid chromatographic method for determining acetaminophen in human plasma. Acetaminophen is isolated from plasma by adding approximately 200 microL of acetonitrile and 50 mg of solid zinc sulfate to each milliliter of plasma. A short column (60 mm x 4.6 mm) slurry packed with 5.0-microns PRP-1 particles is used with an isocratic elution of 5.0 mM dibasic potassium phosphate and 5.0 mM tetrabutylammonium hydroxide/methanol, 70:30 (v/v). The flow rate is 1.0 mL/min. The acetaminophen peak is detected with a variable wavelength ultraviolet/visible detector at 250 nm and 0.50 to 0.002 AUFS. The analysis time of the assay is less than 15 min, and the limit of detection is 20 ng/mL for an 80-microL injection volume. The pharmacokinetics of acetaminophen in plasma from a subject who had orally ingested 975 mg of the drug in tablet form is conducted using this method, and various pharmacokinetic parameters are determined. PMID- 2925825 TI - Metabolic profiling of urinary organic acids by single and multicolumn capillary gas chromatography. AB - High-resolution gas chromatography (HRGC) and gas chromatography/mass spectrometry (GC/MS) are the techniques of choice to determine the retention indices of more than 200 organic acids as their trimethylsilyl (TMS) or oxime trimethylsilyl derivatives. Several types of apolar and semipolar fused-silica capillary columns (OV-1, SE-52, and OV-1701), used to analyze and separate organic acids isolated from urine samples, are evaluated. PMID- 2925828 TI - Determination of pesticide residues in food with a 6% cyanopropylphenyl capillary column. AB - A small-diameter 6% cyanopropylphenyl column is studied for its suitability for determining pesticides in food. Repeatability and linearity are satisfactory, and the column is capable of separating residue combinations that are known not to separate on methyl silicone columns. At 150 degrees C or 130 degrees C, the column satisfactorily separates five by-products of tecnazene, a growth regulator and sprout suppressant found in potatoes, and four by-products of quintozene, a soil and seed fungicide found in peanut products. PMID- 2925827 TI - Microcomputer-assisted liquid chromatographic separation system: application to toxic compounds identification in poisoned human fluids. AB - The computer-assisted liquid chromatographic system (MCASYST) is developed for automated identification and analysis. The system has six main functions: retention prediction system, liquid chromatographic data base system, automated identification system, optimization of separation conditions, data loading program from UV multichannel detector, and UV spectral data base system. The performance and potential of this MCASYST system is evaluated for toxic compounds identification in poisoned human fluids. PMID- 2925826 TI - Direct determination of chromium(III) and chromium(VI) with ion chromatography using direct current plasma emission as element-selective detector. AB - A method is described that utilizes direct current plasma atomic emission spectrometry as an element-selective method of detection for ion chromatographic determination of chromium(III) and chromium(VI) species. The eluting chromium containing species are detected on the basis of the atomic emission of chromium without any species conversion. Both anion and cation separator columns give similar results when used with varying sample matrices. By employing an on-column preconcentration procedure, the detectable concentrations of the chromium species are reduced to less than 1.0 ppb. This method is applied to the determination of chromium species in human serum, natural water, and industrial process stream samples. PMID- 2925829 TI - Enrichment of tocopherols in wheat germ by directly coupled supercritical fluid extraction with semipreparative supercritical fluid chromatography. AB - Enrichment of tocopherol by coupled supercritical fluid extraction/preparative supercritical fluid chromatography is described. Wheat germ powder is used as the starting material and is subjected to supercritical fluid extraction with carbon dioxide. The extracted oil containing tocopherols is concentrated and trapped on a silica gel column by reducing the pressure of carbon dioxide. The trapped oil is then eluted and separated on a silica gel column of 20 mm i.d. x 20 mm length. The column effluent is fractionated by monitoring UV absorption at 290 nm. With this method, tocopherol content of the wheat germ is enriched 100-fold. PMID- 2925830 TI - High-performance liquid chromatographic analysis of steroid hormones. AB - In the present work, a practical, rapid, reliable and isocratic reversed-phase high-performance liquid chromatographic (HPLC) method is described for the qualitative and quantitative analysis of estriol, estradiol-17 beta, estrone, testosterone, and progesterone. Chromatographic separation is complete in 16 min using a mobile phase of 50% acetonitrile (v/v) in water. The order of elution is estriol, testosterone, estradiol-17 beta, estrone, and progesterone; retention times are 2.5, 5.5, 5.6, 6.9, 16.3 min, respectively. Absorbance maxima of individual steroids is the limiting factor in quantitative determination. The recommended wavelengths for UV monitoring are E3 214, E2 280, T 254, E1 214, and P4 254 nm. PMID- 2925831 TI - Memory functioning following a left medial thalamic hematoma. AB - A patient with a discrete, left medial thalamic hematoma developed a severe anterograde amnesia. The memory deficit was most consistent for verbal materials, but was also observed on several tests of figural memory. The patient appeared to have a normal short-term memory (STM) capacity, performed normally on a STM distractor task and was not abnormally sensitive to proactive inhibition. This case is evidence that unilateral damage to the medial thalamus alone can produce a severe memory deficit. PMID- 2925832 TI - Automatic and attentional mechanisms of semantic priming in Alzheimer's disease. AB - Previous studies using a word-naming task have suggested that in demented patients, semantic priming results only from automatic spreading activation and not from attention-dependent processes. If this is true, then on a lexical decision task where attention-dependent processes are a major source of the semantic-priming effect, demented patients should show little or no priming. To test this prediction, three groups of 16 subjects (young and normal-old individuals and patients with Alzheimer's disease) were given a Word-Naming and a Lexical-Decision task. In both tasks, the amount of semantic priming (the difference in response time to a word preceded by a semantically unassociated vs. a semantically associated word) was determined. Demented patients showed significantly greater semantic priming than either normal group on both tasks. This result argues against the hypothesis that the semantic priming found in demented patients is due solely to automatic processes. PMID- 2925833 TI - Neurobehavioral anomalies in neonates with seizures. AB - Neurobehavioral evaluation of the high-risk neonate represents an important advance in early detection of behavioral anomalies which may give rise to later neuropsychological sequelae. In the present study neonates comprising three diagnostic categories (i.e., respiratory distressed, seizure-disordered, normals) were evaluated with the Brazelton Neonatal Behavior Assessment Scale (BNBAS) to determine the extent to which differences in neurobehavioral organization could be detected with the scale, and how they were related to diagnostic classification. Average conceptional age at testing for the three groups was within the range usually considered full term: e.g., 38.81 weeks (respiratory distressed), 40.18 weeks (normal healthy) and 42.54 weeks (seizure disorder). Infants who had been diagnosed with neonatal seizures exhibited consistently less optimal behavior than did either of the other two groups. Infants with respiratory distress and normal controls did not differ significantly on most summary measures of neurobehavioral organization scored with the BNBAS. The study offers support for the discriminative validity of the BNBAS and its potential usefulness in the assessment of clinically ill newborns. PMID- 2925834 TI - Cholinergic and serotonergic effects on the P3 potential and recent memory. AB - The effects of scopolamine (anticholinergic) and methysergide (antiserotonergic) on memory and long-latency auditory cognitive evoked potentials (EPs) were tested in 16 normal adults. Recent memory was impaired by both drugs. In contrast, scopolamine, but not methysergide, significantly delayed P3 latency and decreased P3 amplitude. Immediate memory and the earlier EP components (i.e., N1 and P2) were unaffected. The findings support the hypothesis that cholinergic neurons are important in the neuronal networks generating the P3 potential. Serotonergic neurons do not appear to play a major role in the networks that generate the P3. PMID- 2925835 TI - Development of a scale for assessment of agitation following traumatic brain injury. AB - Development and initial validation of a scale for assessment of agitation in traumatic brain-injured individuals is described. Items were selected from an initial 39-item pool based on their testability, differentiation of agitation, frequency of occurrence, and representation of the full domain of the construct. The resulting 14-item instrument, called the Agitated Behavior Scale (ABS), was subsequently tested on an independent sample of 35 head-injured subjects. Reliability was examined via measures of internal consistency and qualitative evaluation of principal components factor analysis. Cronbach's alpha exceeded .80 for all rates. Comparable values of theta were found and qualitative criteria of internal consistency were met. The ABS score accounted for between 36% and 62% of the variance in 15 of 16 correlations with simultaneous, independent observations of agitation. Results of initial validation are discussed in light of classic test theory and research necessary for determination of construct validity. PMID- 2925836 TI - Cued recall and memory disorders in dementia. AB - Memory functioning of normal elderly subjects and patients with suspected malignant memory disorders were examined using a cued recall memory assessment procedure. Levels of psychosocial functioning were rated by a multidisciplinary team. Ability to engage in free and cued recall was studied to determine the relationship between problems of acquisition and retrieval. Normal and impaired elderly showed strong differences on free recall and total recall resulting in 90.58% and 79.06% rates of accuracy of prediction of group membership. There were significant multivariate and univariate differences among the memory-impaired groups defined in terms of their psychosocial functioning. These findings indicate that differences in acquisition and retrieval are associated with increasing impairment of psychosocial functioning. Patients whose psychosocial functioning was rated as falling within the questionable range exhibited only deficits in retrieval. Patients whose psychosocial functioning was rated as more severely impaired, exhibited problems of retrieval and acquisition. PMID- 2925837 TI - Wheelchair obstacle course performance in right cerebral vascular accident victims. AB - The initial experiment of this paper investigated the role of hemispatial neglect in wheelchair-related accidents of right-hemisphere stroke victims. Twelve subjects with and 12 subjects without neglect of left space drove their wheelchairs through an obstacle course. Two types of obstacle course errors were evaluated: direct hits and sideswipes. The neglecting group made significantly more direct hits but there were no significant differences between groups in sideswipe errors. In Experiment 2, the nonneglecting group's data were compared with a left-hemisphere stroke group without neglect and three motor control groups to investigate if their errors resulted from motor deficits. The right hemisphere stroke group made significantly more left-sided errors and errors in contralateral space than any other group. In Experiment 3, 13 subjects with neglect were taught to scan to the left which resulted in significant decreases in direct hits but not in sideswipes on the obstacle course. These results suggest that obstacle course performance is sensitive to more than hemispatial neglect. PMID- 2925838 TI - Training functional skills following herpes simplex encephalitis: a single case study. AB - This paper presents a treatment program for the development of personal hygiene behavior in a patient who was 5 years post herpes simplex encephalitis. The patient has severe memory and organizational problems, but is of average overall intelligence. The program consists in part of chaining a series of nine discrete activities by using linking phrases. The program allowed the patient to structure his behavior and wash in a well-organized nonrepetitive way. Results are discussed in the light of previous failures to affect behavior using apparently similar methods. PMID- 2925839 TI - Hemi-inattention in visual search for parallel lines after focal cerebral lesions. AB - Visual search and line orientation discrimination was studied in 67 brain-damaged and 15 control subjects, with the aim of demonstrating that hemi-inattention follows both left- and right-hemisphere damage even when confined to the frontal lobe. Both anterior and posterior lesions of either hemisphere caused inattention to the side contralateral to the lesion, this asymmetry being pronounced at the onset of search, especially in patients with anterior lesions. Hemi-inattention was associated with the overall inefficiency of line orientation discrimination and exploration as well as simple verbal performance in right-hemisphere-damaged patients, but tended to dissociate from these deficits in left hemisphere-damaged patients. Brain-damaged patients were inferior to the control subjects, and women inferior to men in the overall efficiency of exploration, but only women with right posterior lesions had a deficit in line orientation discrimination. PMID- 2925840 TI - Identification and characterization of anti-conjugated azelaic acid antibodies in multiple sclerosis. AB - Human sera from patients with multiple sclerosis (MS) were tested using an enzyme linked immunosorbent assay (ELISA) method on well plates coated with various dicarboxylic acid (C4 to C10) protein conjugates. Specific immunological binding was found with an azelaic acid (AzeA, C9) conjugate. The antibody titer was higher in the sera from the patients in acute relapse than with the progressive form, and higher than that from sera of patients with other neurological diseases and healthy subjects. Modifications of coating concentrations and of antibody dilutions, and experiments with preadsorption enabled determination of binding specificity. Competition experiments with related conjugates demonstrated that the AzeA residue was 167 times better recognized by antibodies from MS patients in acute relapse than those from controls. The suberic and sebasic acid conjugates which only differ from the AzeA conjugate by one methylene group were less well-recognized by MS sera (11 and 47 times, respectively) than the conjugate AzeA-BSA. PMID- 2925842 TI - Effect of cyclosporine on rubella virus-specific immune responses in chronic progressive multiple sclerosis. AB - Cyclosporine A (CsA) has been used in putative autoimmune diseases after sensitization to unknown antigens. We have previously shown that CsA prevented continued activation of T-cells in chronic progressive multiple sclerosis (CPMS) patients. The current study was undertaken to determine whether CsA, or CsA and prednisone (CsA + P) could suppress immune responses to a common recall antigen. Serum antibody levels were higher in all CPMS patients than age-matched normal controls. However, rubella antibody titers in the CsA or CsA + P groups were no different from a placebo-treated CPMS patient group. The lymphocyte responses to inactivated rubella virus of CsA and CsA + P-treated CPMS patients were lower than placebo and control but not statistically different. Therapy with both CSA and CSA + P was associated with significantly lower panel mixed leukocyte responses and Ta1 expression than in the placebo-treated group; CD3, CD4, CD8 antigen expression and active rosette formation by T-cells were similar for the three CPMS groups. These results suggest that while CsA exerts measurable effects on non-specific indicators of cellular immunity in CPMS patients, it may not be as effective in suppressing pre-existent specific immune responses. PMID- 2925841 TI - Extended repertoire of specific antibodies in CSF of patients with subacute sclerosing panencephalitis compared to those with multiple sclerosis: anti bacterial antibodies are also increased. AB - Serum and cerebrospinal fluid (CSF) from eight patients with subacute sclerosing panencephalitis (SSPE), 21 with multiple sclerosis (MS) and 16 controls were analyzed for IgG subclass pattern of anti-viral and anti-bacterial antibodies. In CSF of SSPE and MS patients IgG1 and IgG4 antibodies to measles and IgG1 to mumps were increased compared to the controls. In addition, the SSPE patients had elevated levels of IgG1 to PPD, teichoic acid, and to dextran in CSF. The group of MS patients had decreased levels of IgG1 antibodies to Staphylococcus aureus alpha-toxin. PMID- 2925843 TI - Effect of Mycobacterium leprae-infected Schwann cells and their supernatant on lymphocyte neuroglia interaction. AB - Since the resolution of neural lesions and subsequent nerve damage in leprosy must inevitably involve the participation of immune cells sensitized to Mycobacteria, we have used the dissociated Schwann cell culture model to study the relationship between M. leprae-infected Schwann cells and sensitized immune cells. Our earlier study on light and ultrastructural observations showed that on infection with M. leprae, the cytomorphology of Schwann cells remains unaffected, while degenerative changes suggestive of apoptosis are seen in extraneous lymphocytes which are subsequently phagocytosed by the Schwann cells. We now present additional evidence confirming that the phagocytosis of splenic cells by Schwann cells is indeed a two-step process. The first involves M. leprae dependent cytotoxicity to splenic cells. This is followed by phagocytosis of these cells, which is a secondary and M. leprae-independent phenomenon. This finding has implications particularly on the weak inflammatory response observed in nerve lesions of a majority of lepromatous patients. PMID- 2925844 TI - Molecular analysis of IgA in multiple sclerosis. AB - IgA plays an important role in immune-mediated and anti-viral responses, and is the major antibody in external mucosal secretions. We used enzyme-linked immunosorbent assay (ELISA) and immunoblot to examine IgA in tears and parotid saliva of 21 multiple sclerosis (MS) patients and 19 normal controls. No significant difference in absolute levels were noted and both groups showed a wide range in values. However, 16 of 21 MS patients had detectable changes in molecular form of their IgA. Monomeric IgA was found in 52% of MS tears (P less than 0.001) and 45% of MS parotid saliva (P less than 0.05). Among normals, monomeric IgA was noted in only two saliva samples. IgA in secretions consisted of both A1 and A2 subclasses, although 14% of the monomeric MS IgA samples were restricted to a single subclass. Free secretory component was found in the secretions of all subjects with the exception of a single MS patient. However, immunoblot staining of secretory component was decreased in MS patients compared to controls. This study notes changes in IgA in two distinct external secretions in MS patients compared to controls. These changes are consistent with local mucosal inflammation. Impaired mucosal barriers have important implications in MS with regard to susceptibility to infectious agents, environmental antigen processing, and lymphocyte activation. PMID- 2925845 TI - Experience in the conservative treatment of congenital clubfoot in newborns and infants. AB - We studied 323 children with congenital clubfoot from 1970 to 1987. The principles of conservative treatment of congenital clubfoot in newborns have completely changed since 1973. The present principles we follow are to begin treatment immediately after birth; and adduction and varus removal by manipulation. In each case, we use a plaster cast, which is changed after a few days as long as the foot is limp and well corrigible. The knee is immobilized at 60 to 70 degrees in a plaster cast. During the manipulations, the surgeon's hand presses only the plantar side of the foot. The results can be described as good, since in each child we have removed adduction and varus as operation by posterior release and Achilles lengthening was necessary in only 50% of the children. PMID- 2925846 TI - Critical analysis of results in club feet treated surgically along the Norris Carroll approach: seven years of experience. AB - We have used the Norris Carroll approach to the surgical release of resistant club feet for the last 7 years. Critical analysis of 33 idiopathic club feet, after an average follow-up of 4 years, by clinical and radiological methods showed 82% satisfactory results and 18% unsatisfactory. The results indicated a trend toward limited plantar flexion in these feet, as well as mild supination that disappeared with walking. The advantage of the dual skin incision approach is easy access to both plantar medial and posterolateral structures. The calcaneocuboid joint is released and emphasis is put on release of the lateral tether. PMID- 2925847 TI - Reoperation in treatment of clubfoot. AB - We evaluated 118 operations (including 57 reoperations) on clubfeet. We concluded that relapse is most often the consequence of insufficient primary surgery, and the less sufficient the intervention, the more severe the relapse or residual deformity. The severity of deformity is determined and shown, first of all, by the position of calcaneum. In milder cases, soft tissue operation can prove useful, whereas more severe cases require bony intervention as well. The second, rarer cause of relapse was the fact that the foot was originally stiff and nonreducible. These feet may need multiple reoperations. PMID- 2925848 TI - Treatment of resistant idiopathic pes equinovarus: ten-year experience. AB - Fifty cases of clubfeet (38 children) were evaluated 10 years after surgery. Turco's method was used in 22 cases, while 24 were managed with Achilles tendon lengthening and dorsal capsulotomy. After Turco's operation, good results were achieved in 69% and the deformity recurred in 31%. In the second group, the success rate was 63%. Recurrences are due to insufficient reduction of the talocalcaneonavicular joint. The authors conclude that Achilles tendon lengthening and posterior capsulotomy should be carried out by age 4 months. If by the age of 1 year the foot has not yet assumed its normal position, complete operative reduction is recommended. Preliminary results of histochemical studies of the peroneal muscles are presented. PMID- 2925850 TI - Exaggerated femoral anteversion and acetabular development: experimental study in growing dogs. AB - Femoral excessive anteversion caused by femoral osteotomy in growing dogs is an accurate dynamic model of experimental acetabular dysplasia. Radiographic and CT scan examinations were performed throughout the growing period. Evolution showed an incomplete femoral detorsion. It induced acetabular developmental modification leading to an anterior and superior acetabular dysplasia. At the end of the growing period, hips were not dislocated, but signs of femoral and acetabular osteoarthritis were obvious, which shows the importance of mechanical force modification in the creation of experimental osteoarthritis. The links between hip osteoarthritis and exaggerated femoral anteversion are discussed. Might acetabular dysplasia be secondary to femoral anteversion, which could justify a corrective osteotomy during childhood? Our experiment leads to a better comprehension of this phenomenon. PMID- 2925849 TI - Stirrups as an aid in the treatment of congenital dysplasias of the hip in children. By Arnold Pavlik, 1950. PMID- 2925851 TI - Tibiofibular torsion from the fetal period until birth. AB - The anatomic findings of Le Damany and Dupuis are still valuable as a reference. However, their measurement of tibial torsion does not correspond to clinical conditions. In fact, the torsion of the tibiofibular functional unit corresponds to the angle between the transverse axis of the proximal tibial epiphyseal plate and the axis through the middle of both malleoli. A comparative morphologic, radiologic, computerized axial tomographic and anatomic study performed on 50 fetuses with this definition has shown different results. Tibiofibular torsion was in the clear lateral position from the beginning of the fetal period, with a positive gradient at birth. PMID- 2925852 TI - Double-elevating osteotomy of tibiae in the treatment of severe cases of Blount's disease. AB - The results of operative correction of 13 cases of tibia vara in 10 children with advanced infantile Blount's disease are presented. All of the children were operated by "double-elevating" osteotomy. An essential element of this procedure was the reconstruction of the horizontal level of the medial tibial plateau. The average follow-up after treatment was 8 years 1 month. We recommend this method of osteotomy in cases of considerable depression of the medial tibial condyle with the defect of epiphyseal bone and as a bone bridge between the metaphysis and the epiphysis. PMID- 2925853 TI - Bone formation and remodeling after symmetric and asymmetric physeal distraction. AB - Bone formation after symmetric and asymmetric physeal distraction was studied in growing sheep. After gradual distraction by external fixation, separation of the growth plate occurred. Fluorescence microscopy, microradiography, and histomorphometric methods were used to study neometaphysis formation. The bone was formed from the inner layer of the periosteum to encircle the distraction area, where the osteogenesis occurred according to the collagen bundles. At consolidation, the distraction area was composed of lamellar trabecular and partly woven bone. The bone trabeculae in the distraction area were thicker than in the control radius. After asymmetric physeal distraction, spontaneous correction of the formed angulation occurred through remodeling and asymmetric physeal growth. Although local physeal changes were noted histologically, enchondral growth usually continued after distraction. PMID- 2925855 TI - Preoperative intermittent manual traction in congenital dislocation of the hip. AB - To avoid prolonged hospitalization and the complications of skin and skeletal traction, we have devised a method of intermittent preoperative manual traction in the treatment of congenital dislocation of the hip. Of 60 hips that were followed for more than 1 year, 88.3% had Class I or Class II results according to Severin's criteria. No hip in this series was complicated by avascular necrosis of the proximal femoral epiphysis. PMID- 2925856 TI - CDH diagnosed at 2 to 12 months of age--treatment and results. AB - A treatment program for late-diagnosed CDH included skin traction, arthrography, tenotomy of adductor and psoas tendons, and immobilization of the hips in the "frog leg" position with a plaster cast for 8-12 weeks, followed by an abduction frame until the acetabular dysplasia normalized. Follow-up of 40 children with nonteratological CDH performed 2-12 years after diagnosis revealed 38 normal hips and 2 patients with coxa magna, one of whom had intermittent hip pain. PMID- 2925854 TI - The results of surgical treatment for Perthes' disease. AB - We report the clinical and radiological results following intertrochanteric varus osteotomy and Chiari pelvic osteotomy for Perthes' disease in 70 hips with a minimum follow-up of 3 years. The indication depended on lateralization of the epiphysis of the femoral head with or without full containment in the abduction radiograph, thickening of the acetabular floor, coxa magna, and osteoarthritis. Epiphyseal quotient and sphericity showed that head deformity is mostly permanent; the acetabulum-head quotient provided good coverage. Operation in the condensation stage achieved far better results than later operations. From these and other results, the late and mild occurrence of osteoarthritis can be assumed despite deformed femoral head or acetabulum, with full coverage provided. PMID- 2925857 TI - Injuries of distal clavicular physis in children. AB - We report ten patients (all boys) with distal clavicular physeal injuries. Eighty percent of the injuries occurred on the right side. Nine boys were treated conservatively, but one required operation. Kirschner wire osteosynthesis was performed. Regardless of the type of treatment, all patients healed without functional sequelae. In seven of the nine treated conservatively, however, a deformity of the injured shoulder resulted. I suggest that in cases of great displacement of the central metaphyseal fragment resulting in shortening of the clavicle an open reduction with internal fixation is indicated for cosmetic reasons. PMID- 2925858 TI - New measurement of patellar height in the knees of children using the epiphyseal line midpoint. AB - The height of the patella was reevaluated by the ratio of the distance from the center of the patella to the epiphyseal line midpoint in the proximal tibia (PT) to that between the distances of the distal femur and of the proximal tibia (FT) on 59 knees of 36 normal children whose ages ranged from 3 to 18 years (average 10.6 years). The averaged ratio of PT to FT was 1.31 +/- 0.9 at full extension and gradually decreased to 0.99 +/- 0.06 at 90 degrees flexion. Changes in value were minimal within the range of 0.99-1.20 in the range of knee flexion from 30 to 90 degrees. PMID- 2925859 TI - False-negative magnetic resonance imaging in early stage of Legg-Calve-Perthes disease. AB - We report a 7-year 6-month-old boy with Legg-Calve-Perthes (LCP) disease in whom a magnetic resonance imaging (MRI) was normal during the early symptomatic phase when the 99mTc bone scintigraphy showed segmental hypoperfusion of the femoral head suggestive of bone infarction. Only later in the disease did the MRI also show the typical changes of LCP. The follow-up on this patient with bilateral disease leaves no doubt about the diagnosis of LCP. This sequence of a positive scintigram before positive MRI findings may be the exception, but it is important to realize that MRI is not always the most sensitive way to diagnose or exclude LCP as suggested hitherto by the literature. PMID- 2925860 TI - Osteochondral defects of the first metatarsal head in adolescence: a stage in the development of hallux rigidus. AB - The cases are presented of five adolescents in whom there was an osteochondral defect of the first metatarsal head. The significance of this lesion is discussed. PMID- 2925861 TI - Considerations in the corticosteroid treatment of bone cysts. AB - To be effective in treating bone cysts, intracavital injections of corticosteroids must be able to run freely over their lining membrane. Free movement may be prevented by complete or partial osseous or fibrous septa or by the cyst contents. This report illustrates such situations. To solve the problem, the interior anatomy of the cyst should be evaluated by a contrast study and then, when necessary, several corticosteroid injections should be made in different cyst compartments. The volume of corticosteroid should be modified according to the size of the cyst. PMID- 2925863 TI - Determinants of self-esteem in children with congenital/acquired limb deficiencies. AB - Social support, family functioning, self-perceptions of appearance, school, behavior, athletics, and social competence, as well as daily hassles/microstressors, were investigated as determinants of general self-esteem in 41 children with congenital/acquired limb deficiencies. Classmate, parent, teacher, and friend social support all were significant predictors of self esteem. Family conflict and organization were also significantly associated with self-esteem, as were microstressors. The overall model of significant predictor variables accounted for 66% of the variance in general self-esteem. General self esteem also was significantly predictive of depressive symptomatology. The findings suggest a number of factors which are potentially modifiable and which might enhance general self-esteem in children with visible physical handicaps. PMID- 2925862 TI - The awareness of primary physicians of the psychosocial adjustment of children with a chronic illness. AB - This study compared primary care physicians' ratings of psychosocial adjustment of their chronically ill pediatric patients with parents' and children's reports. A series of measures of psychosocial adjustment were administered to 63 children with either a seizure disorder or a visible orthopedic condition, and their parents. Each child's physician was asked to rate the presence and severity of psychological adjustment problems in the child, as well as to rate six specific psychosocial domains. Forty-one physicians responded, and relationships between their ratings and child and parent psychosocial measures were determined using Pearson product-moment correlation coefficients. Ratings by physicians correlated with children's reports and parents' judgments about the children, but not with mothers' self-concept or the impact that the illness had on the family. However, physicians' ratings were interdependent. When congruence of physician ratings with child or parent reports was examined for each disease group, we found significant results for the seizure disorder group; however, congruence among ratings for the orthopedically handicapped group was poor. Student's t-tests revealed no statistically significant differences between the two disease groups in any of the demographic variables of the children or physicians, nor in their scores on the criterion measures. Hierarchical multiple regression analysis identified factors that contributed to physicians' significantly different congruence with parents regarding the adjustment of children in the two subsamples. The findings of this study suggested that primary care physicians were moderately aware of the presence and severity of psychosocial adjustment problems in some categories of their pediatric patients with chronic illness.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2925864 TI - Denver developmental activities: a preliminary report. AB - A study was undertaken to develop activity sheets that can be given to parents at the time of child health maintenance visits. A series of 200 activities for parents to undertake with their children were arranged into 11 age groups and four areas: self-care and socialization, speech, small muscle skills, and large muscle skills. A national field test involved 53 private and public practices already using a parent-answered developmental questionnaire. The practices gave the Denver Developmental Activities and survey questionnaires to parents, and completed professional survey questionnaires. Fifty-one professional questionnaires and 79 parent questionnaires were returned. The professionals liked the Activities and did not feel that they slowed their practices. Parents found the Activities enjoyable and easy to understand. Less educated parents reported that the Activities increased their knowledge and prompted them to discuss child development issues with their child's health provider. This survey is considered preliminary, since it was limited to health practices already manifesting interest in child development, and it is not known what percent of parent questionnaires were returned. The latter point precludes one from making generalizations to a larger population. PMID- 2925865 TI - Prospective evaluation of weight gain in both nonorganic and organic failure-to thrive children: an outpatient trial of a multidisciplinary team intervention strategy. AB - Failure-to-thrive (FTT) is categorized as organic (OFTT) or nonorganic (NFTT). Traditionally, it has been taught that children with OFTT are unable to grow well in spite of adequate care (calories, nurturance, medical supervision), whereas NFTT children will grow well when given adequate care. We undertook this study to determine whether NFTT and OFTT children could grow at similar rates when treated by a specialized multidisciplinary team that provided concrete, individualized therapies including psychosocial support, medical care, and hypercaloric diets. Eighty-six children were enrolled on referral to our outpatient FTT consultative clinic; 64 had NFTT and 22 had OFTT. Growth quotient analysis was used to determine growth outcomes over a 6-month follow-up period. Growth at a rate paralleling the growth curve produces a GQ equal to 1. Growth 2 times as rapid as expected gives a GQ = 2. Children in both groups grew extremely well. For NFTT, GQ = 1.67 +/- 0.56 (SD); for OFTT, GQ = 1.81 +/- 0.37 (SD), p = NS. OFTT children grew just as well as NFTT children when given adequate calories for catch-up growth. Our data indicate that weight gain alone cannot reliably differentiate OFTT from NFTT, as has been traditionally taught. They suggest that we make every attempt to maximize caloric intake in FTT children. They also suggest that a multidisciplinary team consisting of a pediatrician, child psychiatrist, nutritionist, nurse clinician, and social worker may be successful in managing FTT children. PMID- 2925866 TI - Children who were very low birth weight: development and academic achievement at nine years of age. AB - Children born at very low birth weights (VLBW) (less than or equal to 1500 g) who were beneficiaries of modern neonatal intensive care are reaching middle childhood, and their school achievement can be evaluated. We compared 65 9-year old children born in 1976, who were very low birth weight and who were free of neurological impairment, with 65 children of normal birth weight who had been matched for race, sex, age, and social class on measures of IQ, cognitive, visuo motor, and fine motor abilities, and academic achievement. VLBW children scored significantly lower than controls on the WISC-R, Bender-Gestalt, Purdue Pegboard, subtests from the Woodcock Johnson Cognitive Abilities Battery, and reading and mathematics (math) achievement. Exploratory analysis of a subset of 43 VLBW and matched controls with IQ scores greater than or equal to 85 yielded a similar trend, except that, on achievement tests, differences were significant only in math. Further analyses revealed that the differential in math achievement between VLBW and control children is not fully attributable to differences in IQ. PMID- 2925867 TI - Stability of systolic blood pressure reactivity to exercise in young children. AB - Blood pressure reactivity to stress in childhood has predicted development of hypertension 45 years later, so it is important to understand the characteristics of blood pressure reactivity in childhood. The present study assessed the 1-week and 6-month stability of systolic blood pressure reactivity to a 40-meter run stressor in preschool children. Sixty-three low-income children (mean age, 3.9 years) were assessed on four different days over a 6-month period. One-week stability (r = 0.39 to 0.50) and 6-month stability (r = 0.56) of reactive systolic blood pressure levels were highly significant. Reactive systolic blood pressure level was more stable than resting systolic or diastolic blood pressure in this sample. Sex, body mass index, family cardiovascular disease history, and child Type A behavior all were unrelated to systolic blood pressure reactivity. Systolic blood pressure reactivity to exercise appears to be an enduring characteristic that emerges in early childhood. PMID- 2925868 TI - Some thoughts on the value of infant tests for assessing and predicting mental ability. PMID- 2925869 TI - Psychological impact of home apnea monitoring: temporal effects, family resources, and maternal coping style. AB - Mothers of 30 infants who had experienced an emergency apnea episode and were placed on a home apnea monitor were studied longitudinally, using measures of mood disturbance (anxiety, depression, hostility, fatigue, vigor and confusion). Mothers were assessed at the time of hospitalization immediately following the apnea episode, after approximately one month of home monitoring, and after three months of home monitoring. Measures of family resources, health locus of control, and coping style, involving preference for information under situations of threat, were obtained as predictor variables. A high level of mood disturbance was seen initially, but this was transient, diminishing significantly after the first month of monitoring. Level of family resources was highly predictive of mood disturbance throughout the study period, while health locus of control beliefs were predictive of changes in mood disturbance over time. These findings suggest a means for identifying families at higher risk for maladaptive responses, and in need of more intensive psychosocial support. PMID- 2925870 TI - Learning disability in adults: a comparison of two indices of differential cognitive impairment derived from the Wechsler scales. AB - Two indices descriptive of patterns of differential cognitive impairment have been derived from principal component analyses of the normative data of the Wechsler scales for adults (WAIS-R) and children (WISC-R), respectively. The former index is sensitive to the test-specific cognitive effects of unilateral cerebral damage in adults. The latter accurately describes the pattern of subtest scores produced by learning-disabled children. The present study reviews the available WAIS and WAIS-R data from adults with learning disability in order to determine which of these two indices more precisely delineates their pattern of test performance; the index derived from the children's test appears to be the one best able to do so. PMID- 2925871 TI - A comparison of Turkish and Anglo-American normative data on the Wechsler Memory Scale. AB - This study compared the performance of 200 Turkish adults, divided by educational status and age (20-39; 40-59), with published data based upon similar-aged American and British normative samples. Results highlighted the major influence of educational background in determining performance on the WMS and the implications of this effect in interpreting normative performance. PMID- 2925872 TI - Generalizability of WAIS-R factor structure within and between populations. AB - We investigated the reliability of the factor structure of the Wechsler Adult Intelligence Scale-Revised (WAIS-R). The WAIS-R subtests, as administered to 146 head-injured males, were factor analyzed. Two- and three-factor solutions were extracted that were consistent with past findings. Congruence coefficients were computed to determine degree of association between factor structures from all samples reported in the literature. All coefficients were impressive. Also, congruence coefficients based on factor structures derived from different samples within the same population were compared to coefficients based on different samples from different populations. No significant discrepancies emerged. Apparently, the slight factor structure variation that does exist is due to chance data fluctuation rather than to systematic population bias. This reflects well on the robustness of the WAIS-R factor structure. PMID- 2925873 TI - Effects of therapist title on competence as perceived by a psychiatric sample. AB - A study was conducted on how perceptions of a therapist's competence are affected by the therapist's title. Psychiatric inpatients (58 males and 24 females) viewed one of four copies of a videotaped session of the interaction between a male therapist and a male client. One tape described the therapist as "Doctor," one tape described him as "Mister," one by his first name, and one with no name or title. The therapist was rated by the patients on 11 qualities related to competence. Of 11 analyses, 1 title effect was found, and females rated the therapist higher on two qualities. Overall, 9 of the qualities showed no effect for title or for ratings by gender. PMID- 2925874 TI - Effects of mood induction on ratings of self and experimenter. AB - The relationship between depressed mood and subject's trait ratings of self and experimenter was examined. Mood was induced by having subjects (N = 31) view a depressing or control film. Subjects then rated themselves and the experimenter on personality traits related to supportiveness and general ability. Measurement of subject's mood indicated that the mood induction was effective. "Depressed" individuals rated themselves more negatively on the combined personality traits than did controls. "Depressed" individuals rated the experimenter more negatively for supportiveness traits, but slightly more positively for general ability traits than did control subjects. Results are discussed in terms of research on the effects of depression on self-devaluation and support seeking. PMID- 2925875 TI - Identity integration and ego pathology in disturbed adolescents. AB - Utilizing the Rorschach and the Wechsler, groups of borderline adolescents (n = 26) and adolescents with other personality disorders (n = 26) were compared to determine whether there were differences in magnitude and type of disturbances in ego functioning. The specific aspects of ego functioning that were studied included disturbances in identity integration, reliance on primitive defensive operations, vulnerability to regressive thinking, and lapses in reality appreciation. Results indicated that during adolescence the borderline personality represents a more severe form of character pathology than other personality disorders, as revealed by more disturbances in identity integration, a greater regression to primary-process thinking in unstructured settings, and more frequent lapses in reality testing. This contrast was most striking in the area of identity integration, where identity disturbances tended to be associated with lapses in reality testing in borderline adolescents, while there was essentially no relationship between these two indicators of ego pathology in non borderline adolescents. This supports the notion that disturbances in identity integration, or the sense of self, form an important part of the borderline diagnosis, even during adolescence. PMID- 2925876 TI - Cluster analytically derived MMPI profile subgroups of incarcerated adult rapists. AB - Sex offenders are known to be heterogeneous in their patterns of personality functioning and behavior. The present study conducted a multivariate cluster analysis on the MMPIs of 120 incarcerated adult male rapists. The analysis resulted in the identification of five MMPI profile subgroups. Additional differences among subgroups were identified in the circumstances of the crime and responses to the Multiphasic Sex Inventory. Levels of psychopathology, as indicated by the MMPI, ranged from slight to extreme. Results are discussed with reference to previous MMPI research with sex offenders. Suggestions for future research are offered. PMID- 2925877 TI - Normative data on the Kagan Matching Familiar Figures test for adult male incarcerates. AB - This study presents normative data on the Kagan Matching Familiar Figures test, a measure of impulsivity/reflection, for 200 adult male incarcerates (108 Black, 92 White) in a state correctional system. Also presented are t-tests between groups and correlations between the MFF and a series of demographic and test measures. Low, significant correlations were found between the MFF scores (time, number correct) and race, IQ, education, and reading levels. A comparison with college male and female norms is provided. The value and use of the MFF as a measure of cognitive style are discussed. PMID- 2925878 TI - Personality and symptom characteristics of continuous vs. episodic drinkers. AB - This study was designed to identify clinically meaningful differences between Continuous and Episodic Drinkers who were entering inpatient treatment on the basis of demographic, social functioning, and drinking information, as well as scores based on an intake administration of the Millon Clinical Multiaxial Inventory. A discriminant analysis correctly classified 79% of patients into Continuous and Episodic Drinking groups. Variables that had both interpretable loadings on the discriminant function and scores that were associated positively with membership in the Continuous Drinking group include the Psychotic Thinking, Passive-Aggressive, Avoidant, and Psychotic Depression scales of the MCMI and a questionnaire item, "Drinking helps me to work better." In contrast, scores on the Conforming-Compulsive scale of the MCMI were associated positively with membership in the Episodic Drinking group. PMID- 2925879 TI - Antecedents of gregarious alcoholism: an a priori model. AB - Path analysis procedures were used to test a causal model that concerns possible antecedent conditions in relation to gregarious drinking patterns. Selected scales from The California Psychological Inventory (CPI) and The Alcohol Use Inventory (AUI) constituted the assessments. The model was partially corroborated with reference to a group of 40 alcoholics (32 males; 8 females; M age = 33) in an outpatient treatment setting. The presumed causal variables accounted for 26% of the variance in self-reported gregarious drinking. Support was obtained for the assumption that certain interpersonal deficiencies may combine with beliefs in social benefits via alcohol usage to produce gregarious alcoholism. PMID- 2925880 TI - Attitudes of clinical psychologists toward the social relevancy of clinical psychology. AB - Perceptions and attitudes of academic and applied clinical psychologists with regard to social psychology and several aspects of clinical psychology were compared, as were possible changes in perceptions over a 15-year period. Theory, research, and practice generally were seen as more relevant in 1984 than in 1969, particularly among the applied respondents. However, many of the academic and applied respondents continue to believe that the work in these areas is not highly socially relevant. PMID- 2925881 TI - Anxiety in medical situations: adult cancer patients. AB - Anxiety associated with medical situations was studied in a heterogeneous sample of 320 adult cancer patients. Patients completed the Cancer Inventory of Problem Situations, which identifies anxiety in a variety of medical situations. On the average, 44% of patients reported some anxiety in medical situations; 23% reported significant anxiety. Anxiety was somewhat situation dependent. Females were more likely to report anxiety and with greater intensity than males in situations such as watching other patients receive treatments, waiting to see the doctor, waiting to find out the results of tests, going to the hospital, and receiving chemotherapy. Multiple regression techniques were used to identify the correlates of anxiety. Age, sex, problems communicating with the health team, and global adjustment to the illness all accounted for a significant amount of the variance. The results suggest important areas for mental health professionals to be involved in the care of individuals with cancer if comprehensive care is to be provided. PMID- 2925882 TI - Dimensions of coping that contribute to psychopathology. AB - In an attempt to clarify the components of coping that relate to psychopathology, this study evaluated the simultaneous contribution of coping ability and coping actually executed, as well as the independent contribution of each, to psychopathology. Ninety female college students served as the primary sample, while an additional sample of 90 female college students served as the cross validation sample. Each subject completed the MMPI and two versions of the Ways of Coping Checklist. Findings suggest that, while coping actually executed and coping ability show substantial overlap, both components of coping independently contribute unique variance to psychopathology. Implications for coping research and theory are discussed. PMID- 2925883 TI - IQ as a prognostic indicator in adult psychiatric first-admissions. AB - This study used IQ, along with measures of premorbid adjustment, health-sickness, symptom level, diagnostic severity and demographic data, to predict to 2-year outcome measures of level of functioning, health-sickness, and symptoms for a sample of 145 adult psychiatric first-admissions. It was hypothesized that IQ as an indicator of cognitive ability, or of general ability to adapt, would predict positively to improvement over the 2-year period. Data analysis was conducted with bivariate correlations and multiple regressions, using both absolute-level and residualized outcome variables. IQ showed modest, significant relationships with all absolute outcome indices and six of seven residualized measures, especially for a subsample of those with non-average IQ scores. Regressions showed that IQ provided independent prediction of symptom outcomes. PMID- 2925884 TI - Self-reported depressive symptomatology, mood ratings, and treatment outcome in sleep disorders patients. AB - Based on self-rating questionnaire evaluation of symptoms of major affective disorder, 67% of patients who presented to a major sleep disorders center reported an episode of depression within the previous 5 years, and 26% described themselves as depressed at presentation. Furthermore, patients with sleep apnea, narcolepsy, or sleep-related periodic leg movements all averaged high rates of self-reported depressive symptomatology, which suggests that sleep disorders should be considered in the differential diagnosis of affective disorders, and vice versa. Change scores on the Profile of Mood States were obtained for four subgroups of patients who were undergoing conventional treatment. Significant improvement in scores was observed in obstructive sleep apneics treated surgically and in patients with sleep-related periodic leg movements placed on clonazepam, but not in narcoleptics placed on a stimulant or in insomniacs with chronic use of sedative-hypnotic drugs who were withdrawn from sleep medications. Differential improvement in POMS scores after treatment for different sleep disorders could mean that the relationship to mood disturbance differs for different sleep disorders. PMID- 2925886 TI - Factor structure of a brief symptom checklist for acute psychiatric inpatients. AB - A 36-item symptom checklist (the HSCL-36) was assembled and assessed based on previous factor-analytic research with the Hopkins Symptom Checklist-90 (HSCL 90), which had focused on outpatients. Acute psychiatric inpatients (N = 243) completed the HSCL-36 after admission to a university hospital. The responses were factor analyzed using a principal axis extraction. Varimax rotation yielded six interpretable factors, for which factor-based subscales were derived. Five of the six subscales were found to be reliable using coefficient alpha. Results are compared with studies that used self-report symptom checklists with outpatients. Future directions for research are discussed. PMID- 2925885 TI - Relationship of body-image distortion to sex-role identifications, irrational cognitions, and body weight in eating-disordered females. AB - Thirty-one eating-disordered (ED) women and 11 normal women completed tests of sex-role identity, dysfunctional cognitions, and body image. Anorexics, not bulimics, exhibited body-image distortion. All EDs (distorters and nondistorters) showed "hyperfeminine" identifications. Maladaptive cognitions were present in all EDs, but more marked in "overestimators." Body weight predicted BID better than other measures of eating pathology, which suggests important effects of weight per se in producing BID. PMID- 2925887 TI - Civilian-related post-traumatic stress disorder: assessment-related issues. AB - The psychological characteristics of civilians (N = 26) with a post-traumatic stress disorder (PTSD) were investigated in order to determine whether the assessment and diagnostic decision rules developed using the MMPI with combat related PTSD apply to civilian-related PTSD. The results indicate that there are substantial differences between the two PTSD populations and that further research is warranted to delineate other qualitative and quantitative aspects. PMID- 2925888 TI - Psychometric detection of fabricated symptoms of combat-related post-traumatic stress disorder: a systematic replication. AB - Vietnam veterans with post-traumatic stress disorder (n = 11) and two other groups of Vietnam veterans (n = 24) instructed to fabricate symptoms of post traumatic stress disorder completed the MMPI. A discriminant function analysis that used scale F and the post-traumatic stress disorder subscale correctly classified 91% of the subjects. This systematic replication supports the utility of the MMPI as a component in evaluating the validity of self-reported symptoms of post-traumatic stress disorder in Vietnam veterans. PMID- 2925889 TI - The MCMI-II as a treatment outcome measure for psychiatric inpatients. AB - Recently, the MCMI-II (Millon, 1987) has been introduced as a successor to the MCMI-I (Millon, 1983). This study evaluated the MCMI-II as a treatment outcome measure for psychiatric inpatients. Ninety-eight patients were tested at admission and discharge with the MCMI-II. Changes in mean MCMI-II scores on the basic and pathological personality scales, as well as the moderate and severe symptom scales, were generally congruent with findings from a previous outcome study with the MCMI-I (Piersma, 1986a). However, several differences between the MCMI-II and MCMI-I were noted, which suggests that the MCMI-II will need to be cross-validated as an instrument distinct from the MCMI-I. PMID- 2925890 TI - Relative efficacy of the Sc-O, P-O, P-N, and Sc MMPI scales in differentiating brain-damaged, brain-damaged schizophrenic, schizophrenic, and somatoform disorders in an outpatient setting. AB - This study examined the efficacy of the Schizophrenic-Organicity (Sc-O), Psychiatric-Organic (P-O), the Pseudo-Neurological (P-N), and the Schizophrenia (Sc) MMPI subscales in differentiating the following four groups of outpatients: brain-damaged (n = 35), brain-damaged schizophrenics (n = 10), non-brain-damaged schizophrenics (n = 15), and somatoform disorders (n = 45). Both unmatched and matched samples were used in the analysis, and cut-off scores were obtained. In an unmatched sample, results suggested that the Sc scale was useful in differentiating brain-damaged schizophrenics from brain-damaged and somatoform disorders. With matched samples, the Sc differentiated brain-damaged schizophrenics well from other clinical groups, while the P-O scale differentiated the non-brain-damaged schizophrenics from brain-damaged and somatoform disorders. Furthermore, the P-N scale discriminated brain-damaged schizophrenics from non-brain-damaged schizophrenics, while the Sc-O scale was no longer significant. Results suggest that caution should be used in generalizing from previous studies (which used inpatient samples) to outpatient populations. PMID- 2925891 TI - Age changes in axon number along the cervical ventral spinal nerve roots in rats. AB - Axon counts were made at two standardised levels of C7 ventral spinal nerve roots from 46 female rats representing nine ages between birth and 500 days. The objective was to provide a definitive account of proximodistal changes in axon numbers and of age changes in axon numbers both during postnatal development and at several stages during maturity. At each age there is a proximodistal increase in the numbers of axons in all categories examined (myelinated, promyelin, transitional, and fetal) between levels midway along the subarachnoid course of the root and where it is apposed to but separate from the dorsal root ganglion. During maturation and throughout maturity axon totals change similarly at both levels: After a slight increase immediately postnatum, they decline sharply between 4 and 20 days due to a marked loss of unmyelinated axons. A gradual decline in myelinated axon numbers continues to 500 days. While these changes are occurring, axon numbers in all categories show a proximodistal increase throughout. The magnitude of this increase lessens with age for all but the transitional category due to a preferential decrease in numbers distally. Though these observations do not differentiate between axon branching and looping of sensory axons into the ventral root as a cause of the proximodistal increase in numbers, they tend to support the former. At each age during maturation axon proportions at proximal and distal levels correspond well for each animal, indicating that axon segregation proceeds at related rates within each root. Age changes in axon proportions within the transitional and fetal categories indicate that the postnatal stage of axon segregation results from axon loss, rather than Schwann cell proliferation. PMID- 2925892 TI - Calcium-binding protein (calbindin-D28k) and parvalbumin immunocytochemistry: localization in the rat hippocampus with specific reference to the selective vulnerability of hippocampal neurons to seizure activity. AB - Two neuronal calcium-binding proteins, calbindin-D28k (CaBP) and parvalbumin (PV), were localized in the normal rat hippocampus by using immunocytochemical methods to determine 1) their location and 2) whether a correlation exists between the presence of these two calcium-binding proteins and the selective vulnerability of different hippocampal neuronal populations to experimental seizure activity. CaBP-like immunoreactivity (CaBP-LI) is present in all dentate granule cells and some, but not all, CA1 and CA2 pyramidal cells. Some CA1 pyramidal cells lack CaBP-LI, and those that do are lightly stained compared to the dentate granule cells. CA3 pyramidal cells appear to contain neither CaBP- nor PV-LI, and no granule or pyramidal cells exhibit PV-LI. CaBP-LI is present in distinct populations of dentate and hippocampal interneurons but absent from others. In area dentata, CaBP-LI is present in a small number of interneurons of the molecular and granule cell layers and in a small population of presumed basket cells in or below the granule cell layer. Conversely, more presumed dentate basket cells exhibit PV-LI than CaBP-LI. In the hilus of area dentata, few cells are CaBP- or PV-immunoreactive. The hilar somatostatin/neuropeptide Y (NPY)-immunoreactive cells and hilar mossy cells, two distinct and large populations, lack CaBP- and PV-LI. In the CA3 region, CaBP-LI is present in a relatively small number of interneurons in each stratum. PV-immunoreactive interneurons in area CA3 are more numerous. In area CA1, CaBP-LI is present in many interneurons in strata radiatum and lacunosum-moleculare. Some, but relatively fewer, CaBP-positive interneurons are present in strata pyramidale and oriens. Conversely, PV-immunoreactive interneurons are numerous in strata pyramidale and oriens but rare in strata radiatum and lacunosum-moleculare. Staining with the particulate chromagen benzidine hydrochloride revealed a previously undescribed dense band of CaBP-LI in the inner dentate molecular layer, a lamina enriched with kainate-displaceable glutamate-binding sites and innervated by the apparently excitatory ipsilateral associational/commissural (IAC) pathway that originates in the CaBP-negative hilar mossy cells. Bilateral electrical stimulation of the perforant path was performed in order to destroy the hilar mossy cells and to determine if this band of CaBP-LI is normally present within the mossy cell terminals. Perforant path stimulation that destroyed hilar mossy cells throughout the dorsal portions of both hippocampi did not abolish the dense CaBP-like immunoreactivity in the inner molecular layer. PMID- 2925893 TI - Forms and measures of adult and developing human corpus callosum: is there sexual dimorphism? AB - The sexual dimorphism of the human corpus callosum (CC) is currently controversial, possibly because of difficulties in morphometric analysis. We have reinvestigated the issue by using morphometric techniques specially designed to yield objective measurements of CC size and shape. The development of the CC was studied with similar techniques in order to investigate whether its final shape and size might be influenced by axonal elimination, as could be expected from previous animal studies. We have measured the CCs of 32 men and 26 women; 27 male and 19 female CCs were from brain tissue, the others were from magnetic resonance imaging graphs. Women tended to have 1) a smaller cross-sectional callosal area (CCA); 2) a larger fraction of CCA in the posterior fifth of the CC; 3) more slender CCs; and 4) more bulbous splenia. These differences could not be detected by simple inspection but were demonstrated by measurement and statistical analysis. However, CCA was correlated with the other sexually dimorphic parameters, and the sex-related differences in the latter became nonsignificant when variations in CCA were factored out or when male and female populations with similar CCA were compared. In addition, we analyzed CCs of 16 male and 16 female fetuses and of 13 male and 15 female infants and children. This sample ranged in age between 20 weeks of gestation and 14 years but covered in detail the period up to 14 months after birth. CCA increased throughout the latter period but decreased slightly between about 33 weeks of gestation and the beginning of the second postnatal mouth. This decrease coincided with thinning of the CC and a marked increase in bulbosity of the splenium. No sexual dimorphism could be demonstrated until the beginning of the postnatal period. In the age group between birth (at term) and the 14th month, CCA was, as in the adult, larger in males. Unlike in the adults, the CC was longer in males and the bulbosity index was the same in the two sexes. Axonal elimination may play a role in the perinatal pause in CCA growth and in the concomitant changes in callosal shape. PMID- 2925894 TI - Organization of the GABAergic system in the rat hippocampal formation: a quantitative immunocytochemical study. AB - Specific antibodies against gamma aminobutyric acid (GABA) and glutamic acid decarboxylase (GAD) were used to study the organization of the GABAergic system in the rat hippocampal formation. Both the number of GABA-like-immunoreactive (Li) somata and neuropil density were assessed in semithin sections. Cell counts revealed that approximately 11% of the hippocampal neuronal population showed GABA-Li within the various planes of section. Each layer in the hippocampal formation had a characteristic organization of GABA-Li elements. In Ammon's horn, 80-95% of the neuronal somata within the apical and basal dendritic regions were GABA-Li positive. Within the pyramidal cell layer 5-8% of the cells were GABA-Li in the CA1 to CA3 subfields of Ammon's horn and only 3% were GABA-Li within that portion of the pyramidal cell layer that inserts into the hilus. Only slight differences in the density of the GABA-Li neuropil were observed within the CA1 CA3 dendritic regions. Restricted to the stratum lucidum was a dense band of GABA Li label. Counts of immunoreactive grains localized on the perimeter of pyramidal (CA1-CA3) and granule somata revealed more terminal boutons on the CA3 cells than on CA1 and granule neuronal somata. A topographical distribution of GABA-Li somata and neuropil was found in the fascia dentata: There the label particularly concerned its suprapyramidal and rostrolateral portions. Approximately 40% of neurons in the molecular layer, 60% in the polymorph layer, and 18% within the hilar region were GABA-Li. Within the granule cell layer only 2% of the neurons were GABA-Li positive. Distinct differences in the density of the GABA-Li neuropil were present in the molecular, pericellular granular, and hilar regions of the fascia dentata. While the morphology of GABA-Li neuronal somata varied according to their hippocampal layer, the most heterogeneous cell types were found in the regio inferior of the hippocampus. There we have identified neurons that are reminiscent of the inferior region interneuron described in Golgi material by Amaral and Woodward (Brain Res. 124:225-236, '77). Moreover, particularly in the sagittal plane, we have identified oval, triangular, and round cells and that have processes oriented in a parallel arrangement, appearing to be aligned along the granule cell mossy fibers. PMID- 2925895 TI - Development of the thalamocortical system: transient-crossed projections to the frontal cortex in neonatal rats. AB - The developmental remodeling of thalamic projections to frontal and prefrontal cortical fields was investigated in the rat by using a double retrograde tracing technique. Bilateral cortical injections of fluorescent tracers were made either in neonatal (first or second postnatal day) or in adult animals. In neonates, the cell populations retrogradely labeled from each cortical injection overlapped in a medial thalamic region that included the midline nuclei and the medial part of the mediodorsal nucleus, ventral medial nucleus, and nucleus gelatinosus. In adults, the overlap region was confined within the boundaries of the midline nuclei. Quantitative analysis showed that this overlap area was three times as wide in neonates as in adults. The neurons located in this region projected unilaterally both in neonatal and adult animals; bilaterally projecting cells were virtually absent. In neonates, a second set of contralaterally projecting neurons was found in more lateral thalamic regions. This population consisted of cell clusters in the dorsal part of the central lateral nucleus and in the lateral part of the ventral medial nucleus; scattered cells were also observed throughout other nuclei. This second cell population was represented in part by neurons bifurcating bilaterally. In adult animals, neurons projecting contralaterally were observed only occasionally in the lateral thalamus. The present results demonstrate that the bilaterality of thalamocortical projections undergoes a reduction during postnatal development. The mechanisms underlying this remodeling and the possible functional role of the transient-crossed thalamocortical system are discussed. PMID- 2925896 TI - Serotoninergic neurons in the mormyrid brain and their projection to the preelectromotor and primary electrosensory centers: immunohistochemical study. AB - Serotonin-containing neurons in the brain of the weak-electric fish Gnathonemus petersii (mormyridae, teleostei) were studied with the aid of immunohistochemical labeling. Study of the central serotoninergic innervation was focused on the structures subserving the command of the electric organ and the first central relay of the electrosensory system. In the midline raphe nuclei, serotoninergic neurons formed a column that stretched from the ventral caudal medulla to the dorsal midbrain, ending caudal to the cerebellar peduncle. In the dorsal tegmentum, serotoninergic neurons were found bilaterally at the anterior margin of the decussation of the lateral lemniscus. Labeled neurons were also present bilaterally immediately anterior to the cerebellar peduncle and also in the pretectal region. In the hypothalamus, many serotoninergic neurons were in contact with the ventricular wall, and a few were present in the preoptic area. This distribution of serotoninergic cell bodies showed many similarities to that in other fish and higher vertebrates but lacked the lateral spread of the serotoninergic raphe system found in the midbrain tegmentum in mammals. Labeled fibers were found in both the preelectromotor medullary relay nucleus and the electromotor command nucleus. These serotoninergic projections were traced to the posterior raphe. Serotoninergic fibers also formed a dense network in the cortex and in the nucleus of the electrosensory lobe, both of which receive primary input from electroreceptors. These results suggest that serotonin may have a role in the modulation of the intrinsic, rhythmic electromotor command and in the gating of electrosensory input. PMID- 2925897 TI - Cell production in the chicken cochlea. AB - In the chicken cochlea, the structural features of the cilia bundles of individual hair cells vary systematically along the length of the sensory epithelium. As a first approach to understanding the developmental mechanisms that underlie this precise arrangement of structurally distinct hair cells, the spatiotemporal pattern of the terminal mitoses of their precursor cells was investigated by administering 3H-thymidine, a radioactive precursor to DNA. This demonstrated that the first hair cells were produced during the sixth day of incubation and formed a longitudinal band that extended along most of the length of the sensory epithelium. The epithelium grew further through appositional addition of hair cells at the edges of this first band of cells, and the hair cell addition process expanded into the surrounding areas during the next 3 days. By the ninth day of incubation all the hair cells in the sensory epithelium except for those at the peripheral edges in the distal (apex) portion had been produced through terminal mitoses. Our results have demonstrated that hair cells that have similar stereocilia phenotypes do not all leave the mitotic cycle at the same time. PMID- 2925898 TI - Endogenous opioid systems and the regulation of dendritic growth and spine formation. AB - The role of endogenous opioid systems (endogenous opioids and opioid receptors) in neuronal development was examined in 10- and 21-day-old rats by utilizing an opioid antagonist (naltrexone) paradigm. Throughout the first 3 weeks of life, Sprague-Dawley rats were given daily subcutaneous injections of either 50 mg/kg naltrexone, a dosage that invoked a complete (24 hours/day) receptor blockade, or 1 mg/kg naltrexone, a dosage which intermittently blocked (4-6 hours/day) opioid receptors and exacerbated opioid action; animals injected with sterile water served as controls. Pyramidal cells from the frontoparietal cortex (layer III) and hippocampal field CA1, and cerebellar Purkinje cells, were impregnated by using the Golgi-Kopsch method; total and mean dendrite segment length, branch frequency, and spine concentration were analyzed morphometrically. Perturbations of endogenous opioid systems caused region-dependent alterations in dendrite complexity and/or spine concentration in all brain areas. Continuous opioid receptor blockade resulted in dramatic increases in dendrite and/or spine elaboration compared to controls at 10 days in all brain regions; however, these increases were only evident in the hippocampus at 21 days. With intermittent blockade, dendrite and/or spine growth were often subnormal, being predominant at day 21. Our results indicate that endogenous opioid systems are critical regulators of neuronal differentiation, and they control growth through an inhibitory mechanism. Considering previous findings demonstrating that neurobehavioral ontogeny is dependent on endogenous opioid-opioid receptor interactions, the present results suggest an opioid-dependent, structure-function relationship between neuronal and behavioral maturation. PMID- 2925899 TI - Modification of left-right pairing during the development of individual crest synapses in the rat interpeduncular nucleus. AB - The synaptic organization of the rat interpeduncular nucleus is highly ordered in the normal adult. By 90 days of age, 90% of crest synapses in its intermediate subnuclei are formed by two cholinergic endings, one from each medial habenula. Stereological calculation of the number of crest synapses per intermediate subnucleus, based on total samples of crest synapses in 3-4 sections through the subnucleus, allows comparisons of afferent pairing among ages without interference by other developmental changes. Between 21 and 90 days of age, the total number of crest synapses per intermediate subnucleus increases tenfold (p less than 10(-8], from 90,000 at 21 days of age, through 130,000 at 28 days, 440,000 at 45 days, to 1,000,000 at 90 days. The volume of the intermediate subnucleus increases fivefold during the same interval. Electron microscopic degeneration was used to estimate the pairing of left and right habenula afferents at crest synapses at the same ages. Through 21 days of age, only one third of crest synapses are formed with pairing of one left and one right medial habenula afferent, whereas two-third have both afferent endings arising from the same medial habenula. At 28 days of age left-right pairing has increased to 43%, and at 45 days of age 53%, or 240,000, are so paired. The number of same-side paired crest synapses at 45 days, 210,000, is 3.5 times the number so paired at 21 days (p = .003). This indicates continued formation of considerable numbers of crest synapses with this transient mode of airing as late as 45 days of age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2925900 TI - Bouton ultrastructure and synaptic growth in a frog autonomic ganglion. AB - Postmetamorphic growth in the frog, Xenopus laevis, is accompanied by an increase both in the size of autonomic neurons in the heart and in the number of synaptic boutons that contact their surface. To determine whether the properties of individual boutons change as their number increases, serial-section electron microscopy was used to examine bouton ultrastructure at the end of metamorphosis and in the adult. The area of bouton contact, number of active zones per bouton, active zone size, percent of bouton area occupied by active zone, and vesicle density were examined. No differences were found between the two bouton populations for any of the parameters examined. These results support the hypothesis that boutons are structural units of synaptic growth, whereby the total area of synaptic contact increases through the addition of boutons without a change in their morphological properties. PMID- 2925901 TI - Immunocytochemical investigation of L-glutamic acid decarboxylase in the rat hippocampal formation: the influence of transient cerebral ischemia. AB - The hippocampus is especially vulnerable to ischemic damage. Neurons in the CA3c region and dentate hilus demonstrate fast progressive damage while CA1 pyramidal cells demonstrate delayed neuronal damage. The delayed CA1 pyramidal cell loss could be caused by postischemic neuronal hyperactivity if hippocampal interneurons are lost after ischemia. Therefore we have counted the L-glutamic acid decarboxylase (GAD)-immunoreactive neurons in the hippocampus from control rats and rats surviving 4 or 11 days after 20 minutes of cerebral ischemia. All rats were injected intraventricularly with colchicine before they were killed. The hippocampal cell counts showed an increase in GAD-immunoreactive somata visualized on the fourth postischemic day. Eleven days after ischemia, the number of GAD-immunoreactive neurons visualized in the hippocampus CA1 and CA3c region decreased. GAD-immunoreactive baskets were visualized in the pyramidal cell layer and the granule cell layer in controls and 4 days after ischemia, but not in the CA1 and CA3c pyramidal cell layer 11 days after ischemia. We suggest the number of GAD-immunoreactive neurons visualized on the fourth postischemic day increases because somatal GAD accumulation increases and, therefore, ischemia may enhance GAD production. Our previous counts of CA1 interneurons 21 days after ischemia in toluidine-stained semithin sections demonstrated no interneuron loss. Therefore we suggest that the decreased number of CA1 and CA3c GAD-immunoreactive neurons visualized 11 days after ischemia is related to a decreased GAD production. It is possible at this stage after ischemia that the interneurons have decreased their GAD production because they have lost their input and/or target cells. We conclude that our counts of GAD-immunoreactive neurons visualized after ischemia express changes in the content of somatal GAD rather than the actual number of GAD-immunoreactive somata. Finally, we conclude that the delayed loss of CA1 pyramidal cells seen 4 days after ischemia is not preceded by loss of hippocampal GAD-immunoreactive neurons. PMID- 2925902 TI - Origins of the descending spinal projections in petromyzontid and myxinoid agnathans. AB - The origins of the descending spinal pathways in sea lampreys (Petromyzon marinus), silver lampreys (Ichthyomyzon unicuspis), and Pacific hagfish (Eptatretus stouti) were identified by the retrograde transport of horseradish peroxidase (HRP) placed in the rostral spinal cord. In lampreys, the majority of HRP-labeled cells were located along the length of the brainstem reticular formation in the inferior, middle, and superior reticular nuclei of the medulla, mesencephalic tegmentum, and nucleus of the medial longitudinal fasciculus. Labeled reticular cells included the Mauthner and Muller cells. Horseradish peroxidase-filled cells were also present in the descending trigeminal tract, intermediate and posterior octavomotor nuclei, and a diencephalic cell group, the nucleus of the posterior tubercle. As in lampreys, the reticular formation of the Pacific hagfish was the largest source of descending afferents to the spinal cord. Labeled cells were found in the dorsolateral and ventromedial reticular nuclei, the dorsal tegmentum at the juncture of the medulla and midbrain, and the nucleus of the medial longitudinal fasciculus. Additional medullary cells projecting to the cord were located in the perivagal nucleus, the central gray, and the anterior and posterior magnocellular octavolateralis nuclei. The existence of reticulospinal and possible vestibulo-, trigemino-, and solitary spinal projections in lampreys and hagfishes and the wide distribution of these pathways in jawed vertebrates suggest that they evolved in the common ancestor of gnathostomes and both groups of jawless fishes. However, descending spinal pathways from the cerebellum, red nucleus, and telencephalon appear to be gnathostome characters. PMID- 2925903 TI - Frontal lobe connections of the superior temporal sulcus in the rhesus monkey. AB - The frontal lobe connections of different architectonic areas of the superior temporal sulcus (STS) in the rhesus monkey were investigated with the aid of both anterograde and retrograde tracing techniques. The proisocortical area in the rostralmost STS connects with proisocortical regions on the ventral and medial surfaces of the frontal lobe. The frontal lobe projections of polymodal cortex (area TPO) in the upper bank of the STS are organized according to the rostral-to caudal topography of the sulcus. Rostral TPO interconnects with ventral (areas 13, 12, 11, and 14), medial (areas 24, 32, 14, and 9), and lateral (areas 10, 12, and 46) sectors of the frontal lobe. The mid-portion of polymodal cortex projects to, and receives fibers from, rostral subdivisions of lateral prefrontal cortex, viz. dorsal area 46, areas 9 and 10, whereas the caudal segment of TPO has reciprocal connections with caudal subdivisions (areas 46, 8, and 6) of the lateral frontal lobe. Visual-related zones (areas TEa and TEm) in the rostral lower bank of the STS have connectional relationships with orbitofrontal areas 11 and 12 and lateral frontal areas 46 and 8. A presumed somatic sensory-related area in the rostral depth of the STS (area IPa) projects to orbital (areas 11 and 14) and lateral (areas 46, 10, and 12) sectors of the frontal lobe. PMID- 2925904 TI - Metabolic response of glioblastoma to adoptive immunotherapy: detection by phosphorus MR spectroscopy. AB - In a patient with cerebral glioblastoma, metabolic disturbances were detected within the tumor and in the surrounding brain. Within the volume occupied by the tumor, phosphocreatine (PCr)/adenosine triphosphate was reduced and inorganic phosphate/PCr elevated, indicative of tissue necrosis. Loss of total 31P signal was consistent with reduced metabolite content within the area of tumor defined by CT and magnetic resonance (MR). These studies were accomplished with 31P MR spectroscopy at 2 T, using a volume head coil and the technique of two dimensional phase-encoding to map regional metabolism across the entire cerebral cortex in voxels of 30 cm3. Using the same method, only minor variations in 31P metabolism were noted in six normal controls. Treatment with locally placed Interleukin-2 activated lymphocytes resulted in changes in both MR and 31P MR spectroscopy in the region of the tumor. PMID- 2925905 TI - Leigh disease: value of CT in presymptomatic patients and variability of the lesions with time. AB - Three cases of Leigh disease (subacute necrotizing encephalomyelopathy) have been investigated recently in our institute by CT. Bilateral, low attenuation areas were observed in the basal ganglia in all cases. These areas corresponded to the typical necrosis areas seen pathologically in this disease. In our study there were further interesting CT appearances: the peripheral enhancement of low density zones and the discovery of the lesions before the clear onset of clinical symptoms. PMID- 2925906 TI - Significance of thoracic disc herniation demonstrated by MR imaging. AB - The thoracic spines of a group of 48 oncology patients were examined with high field (1.5 T) magnetic resonance (MR) imaging. Sagittal T1-weighted sections were obtained in all patients. Even using this single sequence an unexpectedly high prevalence of thoracic disk herniation (14.5%) was demonstrated. Thoracic disk herniation shown by MR may not be related to the patients' symptoms. PMID- 2925907 TI - Vascular mapping using albumin-(Gd-DTPA), an intravascular MR contrast agent, and projection MR imaging. AB - An intravascular magnetic resonance (MR) contrast agent is valuable for vascular mapping of tissues when used in combination with projection spin-echo MR imaging. The primary advantage of using projection imaging lies in its global depiction of anatomy. Also, relatively short echo time values can be readily achieved, reducing flow dephasing signal losses from blood and increasing overall signal-to noise. These advantages, coupled with the reduction of blood pool T1 values due to the presence of the intravascular contrast agent, allow for detailed spatial mapping of slow-flow vascular structures using MR. PMID- 2925908 TI - CT findings in benign expansions of the larynx. AB - The CT findings in six patients with benign laryngeal expansions are reported. Although CT in laryngeal carcinomas has been extensively dealt with in the literature, little mention has been made of benign conditions. The CT appearances of expansions due to chondroma, tuberculosis, hypertrophic lingual tonsilla, fluid-filled laryngocele, aberrant thyroid adenoma, and chronic granulomatous inflammation are described. PMID- 2925909 TI - MR imaging of superior sulcus carcinoma. AB - Magnetic resonance (MR) imaging was performed in 10 patients with biopsy proven superior sulcus carcinomas to determine the extent of local tumor invasion. Chest wall invasion or extension into the base of the neck was demonstrated in five patients. This finding was facilitated by the contrast between the bright signal intensity of tumor and the low signal intensity of muscle on T2-weighted images. In three patients, MR clearly depicted direct invasion of the mediastinum. This finding was facilitated on the MR image because of inherent contrast between the mediastinal fat and tumor. Coronal and sagittal images showed the relationship of tumor to the subclavian artery and brachial plexus in all cases. Encasement of the artery was confirmed in two cases and brachial plexus involvement in three. However, MR failed to detect evidence of rib destruction in five patients in whom rib involvement was confirmed by other studies. Magnetic resonance appears to be a useful imaging modality in determining the extent of local disease and, therefore, the selection of patients for surgical resection. Multiplanar imaging and contrast between tumor and muscle and tumor and fat allow assessment of invasion of the mediastinum and base of the neck, subclavian artery, and brachial plexus. PMID- 2925910 TI - Pulmonary carcinoid tumors: CT assessment. AB - Computed tomography assessment of 634 surgically proven solitary pulmonary nodules included 12 pulmonary carcinoid tumors. Five were central (involving or directly abutting the bronchial tree), and seven were peripheral (surrounded by parenchyma). Three central and one peripheral lesion had CT numbers indicative of focal calcifications, frequently in the periphery of the nodule. Nodule size ranged from 1.2 to 3 cm. Nine nodules were smooth and round, two were irregular and lobulated, and in one the entire peripheral contour was difficult to assess because of postobstructive atelectasis secondary to tumor occlusion of the bronchus. The calculated average CT number ranged from 80.5 to 179 HU. PMID- 2925911 TI - MR appearance of the normal chest after pneumonectomy. AB - Magnetic resonance (MR) imaging of the chest was performed in nine patients who had undergone pneumonectomy, to evaluate postoperative chest anatomical changes. The main criterion of selection in this study was the absence of cancer recurrence at the time of the study and 6 months later (normal clinical, fiberoptical and cytological data and normal laboratory values). All the MR studies were compared with chest CT performed within 15 days after MR imaging. Postpneumonectomy space revealed in all cases a heterogeneous signal both on T1- and T2-weighted spin-echo sequences. Vascular and bronchial stumps were clearly delineated and surrounded by low signal areas, considered to be postoperative scars. Spatial involvement was well understood with frontal and axial views. Calcifications were poorly identified. Surgical clips were easily detected, but they were difficult to locate accurately. No adverse effects was reported, either in patients with or without surgical clips. PMID- 2925912 TI - The value of CT in rectal villous tumors. AB - Computed tomography of 13 patients with villous rectal tumors was reviewed. Five tumors were benign, eight were malignant. All five benign lesions demonstrated homogeneous focal colonic wall thickening of less than 2 cm. Seven of the eight malignant lesions demonstrated focal colonic wall thickening greater than 2 cm. "Fronds," characterized by contrast within the interstices of the lesion, were seen in three malignant lesions. In the remaining five malignant lesions, three had a polypoid appearance, one had low attenuation regions, and one had focal rectal wall thickening. Computed tomography upstaged two carcinomas, downstaged two carcinomas, and accurately staged four carcinomas. Our experience shows (a) CT can demonstrate the classic fronds of villous tumors; (b) benign villous tumors tend to be less than 2 cm and are nonspecific in appearance; (c) biopsy is necessary to differentiate small malignant lesions from benign lesions; and (d) CT is inaccurate in staging local invasion of malignant villous tumors. PMID- 2925913 TI - Unilateral renal cystic disease: CT findings. AB - Unilateral renal cystic disease (URCD) is characterized by replacement of most of one kidney by multiple cysts scattered diffusely throughout the parenchyma without the formation of a distinct, encapsulated renal mass. There are no cysts in the opposite kidney or liver. The condition is nonfamilial and does not cause renal functional impairment. We describe the clinical and radiologic findings in two patients with URCD and discuss how the disorder usually can be distinguished from other renal cystic diseases using CT. Absence of a family history of renal cystic disease and the normality of the other kidney help distinguish URCD from autosomal dominant polycystic kidney disease. The diffuse nature of the cysts in URCD and the absence of a distinct encapsulated renal mass help distinguish URCD from cystic renal neoplasms. PMID- 2925914 TI - CT and MR imaging in the evaluation of retroperitoneal fibrosis. AB - We have performed CT and MR on five patients with biopsy proven retroperitoneal fibrosis (RPF). Magnetic resonance (MR) accurately displayed a retroperitoneal mass of low signal intensity on T1-weighted scans and of heterogeneous medium signal intensity on T2-weighted scans. The coronal MR views demonstrated a retroperitoneal mass: the shape, signal intensity, and effects on the ureters and major vessels appear characteristic of RPF. PMID- 2925915 TI - Giant cell tumor of the proximal tibia: MR and CT appearance. AB - The magnetic resonance (MR) appearance of four cases of giant cell tumor (GCT) of the proximal tibia are described and the MR grading of these tumors is compared with CT and conventional radiography. Magnetic resonance showed the lesions to be well defined with respect to adjacent marrow and cortical bone. Homogeneous intermediate signal intensity or low signal within the tumors was seen on T1 weighted images. T2-weighted images showed mixed signal intensity with small "bright patches" of increased signal intensity in all four cases. No fluid levels were identified. Magnetic resonance was superior to CT and plain radiography in radiologic grading of the tumors. Computed tomography was superior in determining if cortical invasion was present. Intraarticular tumor extension was more accurately detected by MR and arthrotomography than CT. An MR manifestation of GCT of the proximal tibia is described which may be a common appearance of this tumor by this modality. Magnetic resonance is the procedure of choice in the radiologic grading of GCT. PMID- 2925916 TI - Quantification of knee joint fluid volume by MR imaging and CT using three dimensional data processing. AB - A noninvasive, quantitative technique to estimate joint fluid volume using three dimensional (3D) processing of magnetic resonance (MR) imaging and CT data was evaluated. The mean accuracy error of this 3D approach with MR imaging, performed on five fresh cadaver knees, was -2.4 +/- 5.1% SD when volume estimates were based on heavily T2-weighted transverse images. A considerably higher mean accuracy error of -12.5 +/- 16.9% SD was found when the 3D approach with CT was used (four fresh cadaver knees), probably because of the small attenuation differences between articular soft-tissue structures and joint fluid. A mean precision error of 4.9 +/- 2.3% SD was found when two radiologists independently evaluated in vivo MR imaging studies of 12 knees with joint effusion. Because of the low CT accuracy, no in vivo studies were performed using CT. Thus, this preliminary study shows that quantification of joint fluid volume with 3D data processing offers more accuracy with MR imaging than with CT. The 3D approach with MR imaging provides a potential tool for clinical studies. PMID- 2925917 TI - Validation of three-dimensional reconstructions of knee anatomy: CT vs MR imaging. AB - This is the first investigation to validate the accuracy of spatial measurements based on computer-generated three-dimensional (3D) reconstructions of CT and magnetic resonance (MR) scans. Standard 3D reconstructions of one fresh frozen cadaveric knee specimen with implanted stereotactic reference markers were created. These reconstructions were based on the data from CT and MR scans performed before and after the resection of extraosseous soft tissues. The distances between the stereotactic reference markers in the 3D reconstructions were compared with the same measurements of the specimen using a Bridgeport milling machine as a precision 3D digitizer. The accuracy of intermarker distance measurements averaged 99% for CT-based reconstructions compared with 97.5% for MR based reconstructions. Planar slices at a predetermined level and orientation through the femoral condyles were created by sequential milling of the specimen and were compared with reconstructed oblique planar CT and MR slices at the same level and orientation. The accuracy of condylar dimensional measurements was 94% for CT and 93% for MR compared with measurements of the milled slices. Three dimensional reconstructions based on CT and MR scan data were of equally high quality and were unaffected by the status of the soft tissues. PMID- 2925918 TI - An algorithm for MR imaging of the short T2 fraction of sodium using the FID signal. AB - Multiecho magnetic resonance imaging of 23Na in the human body could provide valuable information regarding the distribution of the sodium in the intracellular and extracellular spaces in living tissues. Since it is known that more than half the intracellular sodium has a T2 value of less than 3 ms, the conventional spin-echo imaging technique is not appropriate for the quantitative study of sodium in living tissues. A pulse sequence using the three-dimensional planar-integral projection reconstruction algorithm was developed to provide images from the free induction decay (FID) signal and from the spin-echo. Using this imaging sequence, we are able to produce human head images with the FID signal immediately following the 90 degrees radiofrequency pulse thus preserving the signal from the very short T2 components. This technique with a multiple echo imaging scheme may open the possibility of discriminating between intracellular and extracellular sodium compartments in the human brain based on the T2 relaxation properties. PMID- 2925919 TI - MR demonstration of reversible brain abnormalities in eclampsia. AB - A 24-year-old woman with eclamptic convulsions during her 25th week of gestation is presented. Magnetic resonance imaging revealed multiple hyperintense foci within the cerebral cortex, most likely related to cerebral ischemia and edema. The MR abnormalities resolved completely within 1 week. PMID- 2925920 TI - CT demonstration of massive cerebral air embolism from pulmonary barotrauma due to cardiopulmonary resuscitation. AB - A 77-year-old man with loss of consciousness, circulatory collapse, and apnea caused by myocardial infarction underwent cardiopulmonary resuscitation with intratracheal intubation and manual bag ventilation. Computed tomography of the head demonstrated massive air embolism in the entire cerebral circulation. The patient was diagnosed as brain dead the next day. Demonstration of massive cerebral air embolism on head CT is presented. PMID- 2925921 TI - Central pontine myelinolysis with clinical recovery: MR documentation. AB - Magnetic resonance (MR) features of a patient with profound hyponatremia and clinical findings of central pontine myelinolysis are presented. Resolution of the MR findings paralleled the clinical recovery. PMID- 2925922 TI - Computed tomography and angiographic findings in metastatic choriocarcinoma. AB - We report a patient with metastatic gestational choriocarcinoma who presented with headaches, speech difficulties, motor aphasia, facial weakness, hemiparesis, and a large intraparenchymal hematoma. She subsequently developed a total of five intraparenchymal hemorrhages. Her clinical presentation posed a diagnostic dilemma and emphasizes the importance of a complete differential diagnosis of multiple intracranial hemorrhages. The features of CNS choriocarcinoma are reviewed. PMID- 2925923 TI - Sequelae of temporal lobe herniation: MR imaging. AB - Acute temporal lobe herniation is a serious complication that may occur with an expanding temporal or parietal lobe mass. Temporal lobe herniation may produce further damage to intracranial structures due to compression or vascular compromise. Differentiation of clinical and imaging abnormalities due to the primary lesion from those related to temporal lobe herniation is essential for proper diagnosis and management. The CT and magnetic resonance findings in a 2 1/2-year-old child who survived severe temporal lobe herniation are reported. PMID- 2925924 TI - Spontaneous dissection of the vertebral artery: MR findings. AB - Spontaneous (nontraumatic) dissection of the carotid and vertebral arteries, once thought to be rare, is being recognized and reported more frequently. We report one case of spontaneous dissection of the vertebral artery initially diagnosed by magnetic resonance imaging and subsequently confirmed by angiography. PMID- 2925925 TI - Post-traumatic spinal synovial cyst with spondylolysis: CT features. AB - A spinal synovial cyst at L2-L3 produced obstruction at myelography and simulated an intraspinal tumor on CT. The CT recognition of bilateral spondylolysis of L3 suggested the possibility of a mobile posterior arch of L3 and associated synovial herniation. This was verified at surgery. PMID- 2925926 TI - Lockjaw secondary to skull base osteochondroma: CT findings. AB - Osteochondromas arising from the long bones, pelvis, or scapulae are common. However, osteochondromas originating from the base of the skull are extremely unusual. Although these tumors are histologically benign, intracranial extension and their close proximity to the cranial nerves may require complex surgery. We present a case in which CT clearly delineated an osteochondroma arising from the base of the skull. The tumor had created a fusion with the ipsilateral coronoid process of the mandible, thus causing lockjaw. PMID- 2925927 TI - Maxillary sinus hemangioma: MR and CT studies. AB - A maxillary sinus hemangioma was detected as an incidental finding during magnetic resonance imaging of the head. The CT findings are more characteristic for the diagnosis of this lesion. Preoperative diagnosis of maxillary sinus hemangioma is important since these lesions can frequently cause a large amount of hemorrhage during surgery. PMID- 2925929 TI - Pulmonary CT findings in Behcet disease. AB - A 32-year-old man with Behcet syndrome presented with hemoptysis and abnormal chest radiography. A 3 cm opacity was present in the apical posterior segment of the left upper lobe and the hila were enlarged with lobulated contours. Computed tomography revealed bilateral pulmonary artery aneurysms, a complication of Behcet syndrome. Computed tomography is recommended for the evaluation of patients with Behcet syndrome who have abnormal chest radiography. PMID- 2925928 TI - Aggressive fibromatosis of the tongue: MR demonstration. AB - A case of aggressive fibromatosis of the tongue is described in a 9-year-old boy. Magnetic resonance was used in the initial evaluation and revealed a well defined mass in the anterior third of the tongue which was mildly hypointense on a T1 weighted image and minimally hyperintense on a T2-weighted image. Magnetic resonance was useful in indicating the benign nature of the tumor, in defining its extent, and for follow-up after local surgical resection. PMID- 2925930 TI - Intracaval and intracardiac extension of malignant thymoma: CT diagnosis. AB - There is disagreement about the ability of CT to detect isolated invasion of mediastinal vessels by malignant thymoma. Diagnosis usually depends on the absence of intact fat planes between the tumor mass and the adjacent vessel. We describe a rare case of CT demonstration of direct intraluminal invasion of a malignant thymoma into the superior vena cava and the right atrium. PMID- 2925931 TI - CT demonstration of right hepatic lobe atrophy. AB - Postoperative bile duct obstruction with subsequent stone formation and infection led to atrophy of the ipsilateral lobe and portal vein obstruction, which promoted further atrophic changes. The compensatory increase in hepatic arterial blood flow resulted in an early enhancement of the atrophic lobe on CT after intravenous contrast medium injection. PMID- 2925932 TI - CT characteristics of intrahepatic, periportal, extramedullary hematopoiesis. AB - A case of primary myelofibrosis that showed intrahepatic periportal extramedullary hematopoiesis on CT and sonography is presented. Pathological correlation of the autopsy material was obtained. It should be included in the differential diagnosis of periportal abnormality on CT. PMID- 2925933 TI - Synovial osteochondromatosis of the shoulder: MR findings. AB - A case of bilateral shoulder synovial osteochondromatosis demonstrated by magnetic resonance (MR) is presented. Shoulder involvement by synovial osteochondromatosis is unusual, and this case demonstrates the characteristic MR findings. PMID- 2925934 TI - Intrinsic third ventricle craniopharyngioma: CT and MR findings. PMID- 2925935 TI - Sphenochoanal polyp: CT findings. PMID- 2925936 TI - Unusually large sialocele: CT characteristics. PMID- 2925937 TI - Disappearance of hemicellulosic monosaccharides and alkali-soluble phenolic compounds of normal and brown midrib sorghum x sudangrasses fed to heifers and sheep. AB - Eight yearling Holstein heifers (330 kg) were utilized in two 4 x 4 Latin squares. Diets were normal and brown midrib genotypes of Redlan x Greenleaf and Redlan x Piper varieties of ensiled first-cutting sorghum-sudangrass harvested at early head stage of maturity. Composition of hemicellulosic monosaccharides and alkali-soluble lignin phenolic compounds in feeds and corresponding digestibilities were estimated. Arabinose, xylose, and uronic acids were more digestible in brown midrib genotypes than in normal genotypes. p-Coumaric acid disappearance was higher in heifers consuming normal genotypes than in those on brown midrib mutants. In a second experiment, four Suffolk wethers with ruminal, duodenal, and ileal cannulae were utilized in a 4 x 4 Latin square design. Diets were second-cutting sorghum-sudangrass harvested at prehead stage of maturity as baled hay. Digestibilities were determined in the same manner as for heifers. Brown midrib genotypes had higher hemicellulosic monosaccharides, galactose, and uronic acids than did normal genotypes. Xylose content of the brown midrib mutant of Redlan x Piper was higher than that of the corresponding normal genotype. Total tract galactose digestibility was higher in brown midrib genotypes than in normal genotypes. Total tract hemicellulose digestibility (estimated by summing fractional digestibilities of hemicellulosic monosaccharides) was higher in brown midrib mutants than in normal genotypes. PMID- 2925939 TI - Digestibility measured by fecal and ileal collection in preruminant calves fed a clotting or a nonclotting milk replacer. AB - Eight Holstein male calves, each fitted with an ileal reentrant cannula at 7 to 10 d of age, were fed a milk replacer based on low heat skim milk powder with or without an oxalate-NaOH buffer known to prevent curd formation in the abomasum. The calves were used to study the effects of milk clotting on digesta flow at the ileum and apparent digestibility measured by fecal and ileal collection. Patterns of ileal flow of total digesta, DM, N, and fat were similar for the clotting and the nonclotting milk replacers. The apparent digestibility of DM and N was higher when measured by fecal than ileal collection for both milk replacers. Digestibility of DM was higher for the clotting than for the nonclotting milk replacer when measured by ileal collection. Clotting did not affect N digestibility measured by either fecal or ileal collection. The concentration of amino acids differed generally in the ileal digesta compared with concentration in feces. In the ileal digesta, some amino acids showed lower concentrations in the clotting milk replacer fed calves compared with those fed the nonclotting milk replacer. The coefficients of digestibility of each amino acid were similar when measured by either fecal or ileal collection. Clotting had no effect on amino acid digestibility measured by both fecal and ileal collection. The data suggest that fecal collection might indicate higher digestibility as compared with ileal collection and that the absence of milk replacer clotting does not affect ileal flow and digestibility of milk replacer N and fat. PMID- 2925938 TI - Disappearance of hemicellulosic monosaccharides and alkali-soluble phenolic compounds of normal and brown midrib sorghum x sundangrass silages fed to Holstein steers. AB - Four ruminally cannulated Holstein steers fed ad libitum were used in a 4 x 4 Latin square design. Feeds were normal and brown midrib genotypes of Redlan x Piper and Redlan x Greenleaf sorghum-sudangrasses. An in situ trial was run in conjunction with the digestibility trial as part of the data collection for each period. Hemicellulosic monosaccharide and alkali-soluble lignin phenolic compound disappearances were quantitated. The xylose to arabinose ratio was higher in normal genotypes than in brown midribs. Normal genotypes had higher concentrations of alkali-soluble p-coumaric acid and lower vanillin, vanillic acid, and sinapic acid than did brown midrib mutants. Disappearance of p-coumaric acid was higher in steers consuming normal genotypes than in those consuming brown midribs. Neutral detergent fiber, acid detergent fiber, hemicellulose, cellulose, and acid detergent lignin showed no genotypic differences in rate of digestion, but extent of 72 h digestion was higher for brown midrib mutants than for normal genotypes. Extent of digestion of the hemicellulosic monosaccharides, xylose, and uronic acids was higher in situ for brown midrib silages compared with normal genotypes. Differences in alkali-soluble phenolic compound and cell wall monosaccharide profiles between normal and brown midrib genotypes may help explain digestibility differences between the two genotypes. PMID- 2925940 TI - Dietary ascorbic acid and immune response in dairy calves. AB - Colostrum-fed, colostrum-deprived, and colostrum-fed and colostrum-deprived calves fed ascorbic acid (1.75 g/d) in whole, raw milk to 6 wk of age were sampled from 0 to 8 wk of age in order to determine whether ascorbate supplementation would increase plasma Ig concentrations, antibody response to immunization, and disease resistance. Plasma IgG concentrations were lower at 14 and 28 d of age in calves fed ascorbate compared with plasma concentrations in calves not receiving ascorbate supplementation, irrespective of colostrum feeding. Colostrum feeding had no effect on antibody titer to keyhole limpet hemocyanin at any age, but ascorbate-supplemented calves had lower plasma antibody titers to keyhole limpet hemocyanin at 35 and 56 d of age. Calves fed ascorbate had lower clinical scores for diarrhea. Dietary ascorbate does not appear to be immunostimulatory in dairy calves to 56 d of age and appeared to inhibit antibody synthesis. However, at 14 d of age there was an interaction of ascorbate supplementation and colostrum feeding; plasma IgG concentrations were higher in colostrum-deprived calves fed ascorbate then in colostrum-deprived calves not fed ascorbate. PMID- 2925941 TI - Tolerance of the calf for excess copper in milk replacer. AB - Calves were fed milk replacer containing 10, 50, 200, 500, or 1000 ppm Cu, from 3 d to 45 d of age, to estimate the Cu concentration that would adversely affect calf performance. Weight gains and feed efficiency were similar for 10 and 50 ppm Cu but were reduced at 200 and 500 ppm Cu. All calves survived 500 ppm Cu and lower intakes, but only 4 of 7 calves survived the 1000 ppm concentration. Typical clinical symptoms of chronic Cu toxicity and hemolytic crisis were evident for the 1000 ppm calves before death. Additional 1000 ppm Zn prevented deaths for 1000 ppm Cu, but calf performance was poor. Increased Cu intakes elevated plasma ceruloplasmin and glutamic oxalacetic transaminase activity, reduced packed cell volume (hematocrit), markedly increased fecal excretion of Mo and Zn, increased Cu concentration of liver, muscle, heart, blood, and bile, and decreased Mo and Zn in liver. We found 50 ppm Cu a safe intake where milk replacer contained 48 ppm Zn and 1.1 ppm Mo. However, at lower intakes of these elements, and for longer feeding periods than 6 wk, the calf may be much more susceptible to Cu toxicity. PMID- 2925942 TI - Detection and quantitation of pea and soy-derived proteins in calf milk replacers. AB - Preruminant calves on several farms had diarrhea nonresponsive to treatment and were doing poorly, despite being fed a high quality calf milk replacer. Because these reconstituted milk replacers always had a sediment, they were suspected of containing insoluble nonmilk-derived proteins. Microscopic examination of the milk replacer, however, did not show any evidence of starch granules. We therefore analyzed the samples by SDS PAGE. We were able to identify and quantitate pea protein in calf milk replacers in which all the protein was supposedly milk-derived. We were also able to differentiate polypeptides derived from pea and soy. We concluded that PAGE is a sensitive technique for detecting nonmilk-derived proteins in calf milk replacers. PMID- 2925943 TI - Genetic effects on dairy calf growth. AB - Objectives were to establish growth patterns for weight and height in dairy calves from birth to 90 d and to estimate appropriate genetic parameters. Measurements were 7943 body weights and 7005 wither heights of 752 calves. Represented over 12 yr were three breeds, 348 dams, and 115 sires; data resulted from designed calf nutrition experiments. Sources of variation considered in various least squares analyses of variance were breed, sire in breed, calf in sire in breed, sex of calf, treatment-year category, and several interactions. Repeatabilities of weights and heights between birth and 90 d were .64 and .88; heritabilities were .22 and .30; genetic and phenotypic correlations were .53 and .73. A regression equation was estimated for each calf. From these 752 equations, heritabilities of initial weight, initial height, and rates of growth in weight and height were .53, .50, .44, and .19. Genetic correlations were .81; -.07; .05; .26; .14; .84. Selection schemes for these traits in dairy cattle should consider that although weights and heights at birth and thereafter are highly and positively correlated genetically, as are gains, birth measurements and gains to 90 d may be uncorrelated. PMID- 2925944 TI - Heritabilities of and genetic correlations among six health problems in Holstein cows. AB - Information from 7712 lactations of Holstein dairy cows was collected from 33 commercial herds around Ithaca, NY in the 3 yr from 1981 to 1983. The data were divided into subsets corresponding to lactation 1, lactation 2, and lactation 3 or greater. To estimate heritabilities of dystocia, retained placenta, metritis, ovarian cysts, milk fever, and mastitis, a mixed linear model (herd-year fixed and sire random effects) with 0 or 1 as the observed response was used. Variance components were estimated using Henderson's Method 3. The results show moderate heritabilities (.15 to .40) for dystocia, metritis, milk fever, and mastitis and low heritability (less than .12) for retained placenta and cystic ovaries. Genetic correlations between dystocia, retained placenta, metritis, and mastitis were moderate in size and positive, whereas cystic ovaries were correlated negatively with dystocia and retained placenta. A general reproductive health trait (dystocia, retained placenta, metritis, cystic ovaries, and milk fever combined in one trait) also was analyzed. The estimated heritability of this trait was .21, .11, and .00 for first calf heifers, second lactation cows, and older cows, respectively. PMID- 2925945 TI - Genetics of reproduction in primiparous Holsteins. AB - Effects of genetics and relationships between yield and days from parturition to first service, first service conception rate, number of services, and a reproductive performance code based on several reproductive components were investigated in primiparous Holsteins. Recorded breedings and DHI production records were from 3393 daughters of 174 bulls in six experimental herds. Subsets included progeny of 78 sires, with greater than or equal to 5 daughters calving in April through July (n = 817) and August through March (n = 1162). Daughter-dam regressions (n = 2593 pairs) and paternal half-sibs were used to estimate heritabilities of fertility traits and associations between yield and reproduction. Results showed increased FCM was associated with lowered fertility. For paternal half-sibs, the greatest antagonism was between conception rates and FCM (rG = -.65 +/- .10). Daughter-dam regressions estimated a favorable genetic correlation of .43 +/- .32 between conception rates and yield. Heritabilities were highest for April through July calvings and ranged from .08 +/- .10 for first service conception to .24 +/- .12 for reproductive code. Correlations between sire least squares constants from warmer and cooler calving seasons were lower than heritabilities of traits would suggest. PMID- 2925946 TI - Effect of treatment with progesterone on pregnancy rate and plasma concentrations of progesterone in Holstein cows. AB - Progesterone-releasing intravaginal devices inserted into the vaginas of dairy cows between d 5 to 12 (n = 28) or d 10 to 17 (n = 27) after insemination increased pregnancy rate to 60 over 30% in untreated control cows (n = 30). Plasma progesterone concentrations were increased during both progesterone treatments. Subtraction of the estimated contribution of exogenous progesterone indicated that endogenous, luteal progesterone was reduced during d 10 to 17 but not during d 5 to 12. Supplemental progesterone increased pregnancy rate but suppressed endogenous production of progesterone when administered during d 10 to 17 after insemination. PMID- 2925947 TI - Conception rates and calving intervals after prostaglandin F2 alpha or prebreeding progesterone in dairy cows. AB - Two experiments were performed in two different herds to determine if utilizing prostaglandin F 2 alpha to induce estrus for first services would be effective in reducing the duration and variability of calving intervals. In Experiment 1, cows were assigned randomly as controls (n = 217) to be inseminated as they were detected in estrus (beginning d 42 to 53 postpartum depending on replicate) or treated with prostaglandin F2 alpha (n = 185). In Experiment 2, the same treatments were utilized, except control cows (n = 124) were inseminated at their first detected estrus after d 40 postpartum, and treated cows received either one injection of prostaglandin F2 alpha between d 54 and 63 (n = 116) or were given progesterone (via a progesterone-releasing intravaginal device) for 7 d, with the device removed 24 h after prostaglandin F2 alpha (n = 116). More cows were inseminated and pregnancy rates were higher within 5 d after treatment with prostaglandin F2 alpha, and interval from prostaglandin F2 alpha to first service was reduced compared with that of control cows. Duration and variation of calving intervals were unaffected in either experiment, despite the fact the elective waiting period was 6 to 23 d longer for treated cows than for controls. Prebreeding treatment with progesterone failed to improve conception rates, but the efficiency of estrous expression increased from 54% in prostaglandin F2 alpha treated cows to 71% in those cows also receiving prebreeding progesterone. We conclude that prostaglandin F2 alpha was ineffective in improving reproductive performance of these herds under good herd management. However, prostaglandin F2 alpha offers the convenience of inseminating small groups of cows, controlling when breedings occur during the work week, and prolonging the elective waiting period without extending the calving interval. PMID- 2925949 TI - Pathology of Staphylococcus aureus mastitis during lactogenesis: relationships with bovine mammary structure and function. AB - Pathological alterations of mammary parenchymal tissue from 5 dairy cows with Staphylococcus aureus mastitis were studied. Tissue from infected quarters exhibited less synthetic and secretory ability during lactogenesis, as indicated by lower percentages of luminal area, but higher percentages of stromal area compared with control tissue. Ultrastructural analysis of alveolar epithelium demonstrated decreased numbers of organelles associated with milk synthesis and secretion. Mammary secretion from 12 additional cows confirmed the loss of secretory potential in infected quarters as concentrations of alpha-lactalbumin were lower during the first 14 d of lactation compared with concentrations from controls. Higher concentrations of serum alpha-lactalbumin from cows with Staphylococcus aureus mastitis suggest leakage of mammary secretion through gaps left by damaged or sloughed alveolar epithelium. Macrophages and lymphocytes were observed frequently in large gaps between basal plasma membrane of secretory cells and the basal lamina which may contribute to epithelial damage. Ability of neutrophils and macrophages to phagocytize staphylococci may have been compromised in the prelactating gland due to the indiscriminate ingestion of accumulated fat and casein. PMID- 2925948 TI - Suppression of mitogenic response of peripheral blood mononuclear cells by bovine mammary secretions. AB - Effects of bovine mammary secretions collected at different stages of the lactation cycle on blood mononuclear cell response to mitogens were evaluated. Mammary secretion skims and wheys collected 7 and 28 d following cessation of milking, at parturition, and during early lactation were used. Colostrum and mammary secretions obtained 7 d after milk cessation were associated with greatest inhibition of mononuclear cell blastogenesis. Milk collected during early lactation caused the least inhibition. Mammary secretion wheys caused greater inhibition of blastogenesis than skims. Dilution of mammary secretions reduced blastogenic inhibition. Phytohemagglutinin-stimulated mononuclear cells were less inhibited by mammary secretion than Concanavalin A-stimulated cells. Suppression of mononuclear cell activity, particularly during early involution and at parturition, may influence susceptibility of the bovine mammary gland to new intramammary infections during physiological transitions of the udder. PMID- 2925950 TI - Bacterial counts in bedding materials used on nine commercial dairies. AB - Bacterial counts were monitored for 1 yr in bedding materials used on nine commercial dairies. Organic materials used to bed lactating cows had significantly higher moisture content and gram-negative bacterial, coliform, Klebsiella species, and streptococcal counts than did inorganic materials. Klebsiella species counts were higher in sawdust than in chopped straw. Streptococcal counts were higher in chopped straw than sawdust. Bacterial counts did not differ between sand and crushed limestone. Gram-negative bacterial and coliform counts were higher during summer and fall than in winter and spring months. Streptococcal counts did not differ among seasons of the year. Linear relationships were significant between total rates of clinical mastitis during lactation and both gram-negative bacterial and Klebsiella species counts in lactating cow bedding. These data indicate that bacterial populations differed between both types of bedding and among seasons of the year. Rates of clinical mastitis were related to bacterial counts in bedding. PMID- 2925951 TI - Relationship of selenium concentrations in blood of calves to blood selenium of the dam and supplemental selenium. AB - Selenium status of dam, injected Se, and dietary Ca on calf blood Se concentrations were determined in two trials. Blood was collected from heifer calf and dam pairs at parturition. Half of the calves were injected intramuscularly with .0825 mg Se/kg body weight at birth while the other half received no Se injections. The concentration of Se in the blood of the dam had a significant effect on blood Se of calves at wk 0, 1, and 3, whereas injected Se did not significantly affect blood Se concentrations in the calf until wk 10. In a separate trial, whole blood and plasma Se were significantly correlated at birth in calves, but plasma Se was only about one-third the concentration of whole blood. The concentration of dietary Ca in the calf starter did not significantly affect blood Se, but a quadratic relationship was suggested. Plasma Zn in calves was elevated at birth and then declined with age whereas plasma inorganic P increased with age. Early postnatal concentrations of Se in blood of calves are largely a function of the dam; thus, in areas of low Se intakes, Se supplements for the dam are important. PMID- 2925952 TI - Refinements in determining the energy value of body tissue reserves and tissue gains from growth. AB - Energy density of weight gain increases with age and weight for age. Gains by more mature cattle contain more fat, less protein, and less water than gains by less mature cattle. The energy density of body tissue reserves mobilized during negative energy balance in early lactation is greater than that in the apparently contributing weight gains. The data reviewed had 140% as much fat and 60% as much protein in mobilized reserves as in gains. These observed differences justified the requantification of the energy density of tissue reserves mobilized for milk synthesis. The energy of gains was estimated by using equations published by the Agricultural Research Council to predict the fat and protein contents of the gains and multiplying them by their respective energy densities. The energy of mobilized reserves (weight losses) were estimated by predicting the fat and protein per kilogram of the contributing gains with the Agricultural Research Council equations, multiplying those fractions by 1.4 and .6, respectively, and multiplying the adjusted fractions by the respective energy densities of fat and protein. There was a close agreement between the predicted and observed energy values of both weight gains and weight losses. PMID- 2925953 TI - Recent research involving the transfer of radionuclides to milk. AB - The radionuclides in milk, which result from exposure of dairy cows to radioactive fallout, are a major factor in assessment of internal radiation of humans. To evaluate the radionuclide intake of people from fallout-contaminated milk requires information about feed sources and milk distribution. Pasture intake and the shelf-life of milk are important factors in the case of a short lived radionuclide like 131I. Large-scale human radiation assessment studies are underway, all of which consider the dairy food chain as a critical component. These include retrospective studies of fallout from nuclear weapons testing at the Nevada site in the 1950s and the impact of the Chernobyl accident on April 26, 1986. PMID- 2925954 TI - Immunogenicity of Bifidobacterium breve and change in antibody production in Peyer's patches after oral administration. AB - Immunogenicity in the intestine of Bifidobacterium breve, included in fermented milk, was compared with that of Bacteroides thetaiotaomicron, also predominant in human intestine. In vivo, serum antibody to B. breve was detected first in mice fed the organism for 33 d; antibody decreased in mice fed these for more than 33 d. Serum antibody to Bact. thetaiotaomicron was detected in mice fed the organism for 7 d and was maintained at the same level in mice fed these for more than 7 d. From in vitro tests, the optimal doses of B. breve and Bact. thetaiotaomicron to induce antibody production by Peyer's patch cells, intestinal lymphoid tissue cells, were 5 x 10(8) and 5 x 10(7) bacteria/ml, respectively. Therefore, it was suggested that immunogenicity of B. breve is weaker than that of Bact. thetaiotaomicron. Furthermore, the change of antibody production to the organism by Peyer's patch cells in the mice administered B. breve orally was tested by the Peyer's patch cell culture method. Antibody production against B. breve by Peyer's patch cells in mice given B. breve for 25 and for 33 d increased and decreased, respectively, in comparison with the control. These results suggest that when serum antibody to B. breve increases significantly, anti-B. breve antibody production by Peyer's patch cells is suppressed, and thereafter, serum antibody to B. breve decrease and is not detected. These findings favor the view that serum antibody production to B. breve is regulated in Peyer's patches. PMID- 2925955 TI - Influence of cholera toxin (an adenylate cyclase activator) on deoxyribonucleic acid synthesis of bovine mammary tissue in vitro and in athymic nude mice. AB - Bovine mammary tissue from midpregnant heifers was placed in explant culture to which chlorea toxin (a potent adenylate cyclase activator) was added (0 to 100 ng/ml). Chlorea toxin increased incorporation of thymidine into DNA in the cultures; response was maximum with 10 ng/ml chlorea toxin and approximately 24 h after addition of cholera toxin. In other studies, bovine mammary tissue was transplanted subcutaneously to ovariectomized athymic nude mice. Subsequent treatment of the mice with cholera toxin alone did not affect growth of bovine mammary tissue. However, treatment with estradiol plus progesterone increased DNA synthesis in epithelial cells. In estradiol plus progesterone-treated mice, cholera toxin injections further increased DNA synthesis. In addition, estradiol plus progesterone treatment in vivo (in athymic nude mice) increased DNA synthesis of bovine mammary tissue in response to cholera toxin in vitro. This synergism between cholera toxin and ovarian steroids may have been mediated, at least in part, by estradiol plus progesterone induction of cyclic AMP dependent protein kinase, as the activity of this enzyme was increased by estradiol plus progesterone. PMID- 2925956 TI - Effect on days of lactation and methionine hydroxy analog on incorporation of plasma fatty acids into plasma triglycerides. AB - Methionine hydroxy analog has been proposed to stimulate hepatic lipoprotein synthesis and incorporation of plasma fatty acids into plasma triglyceride. Seven cows were fed diets containing 0 or 30 g analog/d starting 14 d prepartum. At approximately 30 and 60 d postpartum, cows were continuously infused intravenously with 1-[14C] palmitic acid for 160 min to achieve steady-state labeling of plasma fatty acid and triglyceride. Turnover of fatty acid and transfer quotients for triglyceride and CO2 were 3.3 and 2.7 mmol min-1; 13.0 and 10.0%; and 8.0 and 5.0%, for control and analog, respectively. Proportion of fatty acid turnover incorporated into triglyceride and CO2 were 14.0 and 15.0%; and 21.0 and 18.0, respectively, for control and analog. Analog increased 14C recovered in milk fat (52 vs. 36%). Plasma concentration of fatty acids, percent oxidized to CO2, and percent of CO2 from fatty acids decreased with increasing lactation days. Milk fat percent and yield, fatty acid turnover, and oxidation were positively correlated with concentration of plasma fatty acids, whereas fatty acid incorporated into plasma triglyceride was negatively correlated with fatty acid concentration. The data suggest that hepatic triglyceride secretion is not increased in early lactation; further, no effects of analog on lipid metabolism were detected. PMID- 2925957 TI - Effect of somatotropin on kinetics of nonesterified fatty acids and partition of energy, carbon, and nitrogen in lactating dairy cows. AB - The utilization of energy, carbon, and nitrogen, and irreversible loss rates of nonesterified fatty acids were examined in lactating cows during treatment with bovine somatotropin. Six multiparous Holstein cows at approximately 62 d postpartum received daily intramuscular injections of somatotropin (29.4 mg/d) or excipient during two 21-d treatment periods in a crossover experimental design. Milk yield was increased 11% (37.1 versus 41.3 kg/d), whereas intake and digestibility of DM, energy, nitrogen, and carbon were not affected. Cows remained near zero net energy balance during both treatments (1.31 versus -1.52 Mcal/d for control and somatotropin, respectively). The major effect of somatotropin was to partition net energy into milk while tissue energy accretion was reduced. Postabsorptive use of nitrogen and carbon was altered by somatotropin as reflected by greater secretion in milk. Urinary losses of nitrogen and tissue use of carbon were reduced. Plasma concentrations and irreversible loss rates of nonesterified fatty acids did not differ between treatments. Somatotropin treatment of lactating cows results in partitioning of nutrients away from tissue deposition toward milk synthesis. The extent to which different metabolic processes are altered depends upon the energy balance of the somatotropin-treated animal. PMID- 2925958 TI - Phallometric diagnosis of pedophilia. AB - We investigated the sensitivity of our phallometric test for pedophilia (and hebephilia). An initial sample of subjects included 47 men accused of sexual offenses against minors and 26 control subjects-men accused of offenses against adult women (exhibitionism, rape, or sexually sadistic activity). A second sample included 107 offenders against minors and 30 control subjects. In both samples, the offenders against minors were further classified according to the targets of their sexual offenses (girls, boys, or both) and according to the extent to which they admitted an erotic preference for the immature physique. Computerized diagnostic rules were developed with the first sample and cross-validated with the second. The sensitivity of the test in detecting pedophilia or hebephilia in complete nonadmitters is probably greater than or equal to 55% but is certainly less than 100%. Its specificity appears to be over 95%. PMID- 2925960 TI - Expressed emotion and patient-relative interaction in families of recent onset schizophrenics. AB - This article examines the interaction patterns of relatives of young, recent onset schizophrenic patients classified as displaying either high or low expressed emotion (EE) by two measures, the original Camberwell interview method and a recently developed brief method. The former was administered during the hospitalization period and the latter was administered approximately 2 months later when the patient was in the community. Family interactions were coded with an observational coding system that permitted sequential patterns to be analyzed as a function of the EE status of the family. No relation between the Camberwell EE rating and interactional behavior was found. However, high EE-critical relatives, defined by the brief EE method, were more negative in direct interactions than low EE relatives or high EE relatives classified as emotionally overinvolved. Sequential analyses indicated that high EE-critical relatives showed extreme negative escalation patterns. Patients' reactions to high EE critical relatives were characterized by self-justification and negative nonverbal behavior. PMID- 2925959 TI - Identifying chronic affective disorders in outpatients: validation of the General Behavior Inventory. AB - The validity of the General Behavior Inventory (GBI) in screening outpatients for chronic unipolar and bipolar affective conditions was evaluated. The GBI was administered to 492 consecutive patients at a university clinic and a community mental health center. Using a stratified random sampling plan, 167 patients were selected and administered blind structured diagnostic interviews. In addition, unipolar depressives were followed up 6 months after the initial evaluation. Overall, the GBI exhibited fair-to-good positive predictive power and good-to excellent negative predictive power. In addition, GBI scores in the case range were consistently associated with poor outcome at the 6-month follow-up. These findings suggest that the GBI may provide an economical means of screening for chronic unipolar and bipolar affective conditions in outpatient settings. PMID- 2925961 TI - Neuropsychological test performance and the attention deficit disorders: clinical utility of the Luria-Nebraska Neuropsychological Battery-Children's Revision. AB - The Luria-Nebraska Neuropsychological Battery-Children's Revision (LNNB-CR) was administered to 54 clinic-referred children aged 8-12 years. Children reliably diagnosed as attention deficit disorder with hyperactivity were compared with children diagnosed as attention deficit disorder without hyperactivity and with a clinic control group diagnosed with internalizing disorders. Both attention deficit disorder groups were lower than the control group in verbal and Full Scale IQ scores but did not differ from one another. The groups did not differ significantly on any of the LNNB-CR clinical scales, on the right or left hemisphere scores, or on the pathognomonic score using analyses of variance or analyses of covariance with both Full Scale IQ and age as covariates. These findings failed to support the hypothesis that attention deficit disorder, either with or without hyperactivity, is associated with neuropsychological dysfunction as measured by the LNNB-CR. PMID- 2925962 TI - Styles of self-nurturance and disordered eating. AB - This study explores the relation between self-nurturance and disordered eating. Both structured questionnaires and forms requesting open-ended descriptions of themselves and their parents were administered to bulimic (n = 18), dieting restrainer (n = 20), and nonrestrainer (n = 20) women. The use of food-related and non-food-related forms of nurturance was assessed, as were subjects' reactivity to positive and negative events, levels of dependency, self-criticism, and efficacy. Factor analysis of the various scales yielded three factors: Non Food-Related Self-Nurturance, Negative Reactivity, and Food-Related Self Nurturance. The results indicated that bulimics were less likely to nurture themselves in non-food-related ways and derived a greater percentage of their total self-nurturance from food than both restrainers and nonrestrainers. The results also indicated that bulimics engaged in a greater degree of negative self criticism and reactivity to negative events than nonrestrainers. Differences between bulimics and restrainers are explored in detail. The results are discussed in relation to self-nurturance and its implication for the treatment of bulimia. PMID- 2925963 TI - A psychometric analysis of the sexual arousability index. AB - The Sexual Arousability Index (SAI) assesses self-reported sexual arousal in women and was administered on four occasions to a group of normal sexually active women (n = 57) and to another group undergoing surgical gynecologic treatment (n = 66) that resulted in a predictable and clinical level of sexual dysfunction. These data were used for a psychometric analysis of the SAI. In terms of reliability, internal consistency estimates were in the .92-.96 range, and 4 month test-retest reliabilities ranged from .74 to .90. An evaluation of validity revealed both strengths and limitations of the SAI. The content analysis indicated that at least six domains are sampled, including seduction activities, body caressing, oral-genital and genital stimulation, intercourse, masturbation, and erotic media. To examine construct validity, we conducted a factor analysis that revealed a five-factor solution accounting for 85% of the variance. Furthermore, the factor solution was stable across groups and time, and the factors were sensitive to the occurrence of important behavior changes. The SAI, like other psychological measures, was poor in predicting a criterion (i.e., the occurrence of inhibited sexual excitement) concurrently or at the time of follow up. PMID- 2925964 TI - Power to detect differences between alternative treatments in comparative psychotherapy outcome research. PMID- 2925965 TI - A strategy to use soft data effectively in randomized controlled clinical trials. AB - Soft data are defined as measures having substantial intrasubject variability due to errors of measurement or to the inconsistency of subjects' responses. Such data are often important measures of response in randomized clinical trials. In this context, we show that using an intensive design and the slope of response on time as the outcome measure (a) maximizes sample retention and (b) decreases within-group variability, thus (c) maximizing the power of test procedures without requiring increased sample sizes. PMID- 2925966 TI - Psychological functioning and behavior of sexually abused girls. AB - The psychological functioning and behavior of 46 sexually abused girls (ages 6 14) was compared with that of 46 nonabused girls who were matched on age, race, family income, and family constellation. Sexually abused children demonstrated heightened sexual preoccupation and behavior problems, lower cognitive abilities and school achievement, and more stressful past histories. PMID- 2925967 TI - Effects of running or weight lifting on self-concept in clinically depressed women. AB - Forty clinically depressed women were randomized to a running, weight lifting, or delayed treatment condition. Self-concept was assessed at baseline, pre-, mid-, and posttreatment for all subjects and at 1, 7, and 12 months for exercise groups. Significant improvements in self-concept were found for exercise groups relative to control groups. No significant differences between exercise groups were found, and improvements were reasonably well-maintained over time. Differential changes on dimensions of self-concept were not demonstrated. These results suggest that both running and weight lifting exercise programs improve self-concept in clinically depressed women. PMID- 2925968 TI - Relation of behavioral treatment to "normal functioning": comment on Lovaas. AB - Our commentary is a critique of the Lovaas (1987) study on the outcome of intensive behavioral intervention with young autistic children. Problems in the following aspects of the study are reviewed: (a) the choice of outcome measures, (b) the criteria for subject selection and the intellectual level of the subjects, and (c) the method for assigning subjects to control groups. Based on the available data, we posit that it is not possible to determine the effects of the intervention. PMID- 2925969 TI - Clarifying comments on the young autism study: reply to Schopler, Short, and Mesibov. AB - Lovaas (1987) has been criticized for overstating the outcome of an intensive behavioral intervention for young autistic children. Part of the criticism reflects skepticism of Lovaas's view that it is possible to overcome autistic children's deficits. However, Lovaas's study built on a substantial body of research that has suggested just such a possibility. It also contained a number of methodological features that provide evidence supporting his interpretation of the outcome, notably, unbiased control groups and multiple pretreatment and follow-up measures. PMID- 2925970 TI - Giving up on child psychotherapy: who drops out? Comment on Weisz, Weiss, and Langmeyer. AB - Some critical comments are offered with regard to the use of the designation psychotherapy dropout in the article by Weisz, Weiss, and Langmeyer (1987). It is proposed that individuals who do not begin a course of psychotherapy should not be viewed as dropouts. Reference is also made to problems of generalization. PMID- 2925971 TI - On dropouts and refusers in child psychotherapy: reply to Garfield. AB - We agree with Garfield that there is value in keeping criteria for dropout groups consistent across studies. Because our methods served this goal, we are puzzled at this part of his critique. The term dropout, as used in our study, might reasonably be replaced with Garfield's term refuser; however, the procedural realities of our child clinics make both terms appropriate. At Garfield's suggestion, we present new data on those youngsters he considers true dropouts; analyses reveal that the results we previously reported would have been the same had we used this group. PMID- 2925972 TI - The minimizing of blaming attributions and behaviors in delinquent families. AB - Parents' data were evaluated in three studies of families with a delinquent adolescent. Families were provided with different forms of a positive versus negative interactional (attributional) context. Study 1 demonstrated that the negative context elicited significantly more negative behaviors than did the positive context when parents interacted with each other and with their delinquent adolescent. Study 2 demonstrated that the dispositional attributions of parents were influenced by the manipulation of set, with a dissatisfied set producing negative blaming attributions and a satisfied set producing nonblaming, positive attributions. Study 3 demonstrated that parents' negative sets regarding their adolescent's negative behaviors, once established and discussed by the family for 5 min, were unresponsive to a subsequent positive reattribution regarding those behaviors. Taken together, the data provide some support for reattribution techniques such as relabeling. Yet, the data question the ease with which such techniques can be successful and challenge proponents of such techniques to develop methodologically sound empirical demonstrations of their effectiveness. PMID- 2925973 TI - Behavioral versus insight-oriented marital therapy: effects on individual and interspousal functioning. AB - This study compared the effects of behavioral marital therapy (BMT) and insight oriented marital therapy (IOMT) on both interspousal and intrapersonal functioning in a controlled outcome study. A total of 79 couples seeking treatment for relationship distress were randomly assigned to BMT, IOMT, or a treatment-on-demand (TOD) waiting-list control group. Results indicated the significance in individual and relationship functioning. Both treatment approaches produced significant effects from intake to termination that were substantially maintained at the 6-month follow-up. Behavioral and insight oriented therapies resulted in significant improvements in self-reports of global marital accord and, to a lesser extent, in the reduction of overall psychological distress and in the enhancement of self-concept, with no significant differences between treatment conditions. The magnitude of these effects in comparison with those reported in previous marital outcome studies and in more general psychotherapy research is discussed, and possible mechanisms for the equivalence of these technically divergent treatment approaches are explored. PMID- 2925974 TI - Behavioral intervention to reduce AIDS risk activities. AB - Behavior change can curtail the spread of acquired immune deficiency syndrome (AIDS). In this study, 104 gay men with a history of frequent AIDS high-risk behavior completed self-report, self-monitoring, and behavioral measures related to AIDS risk. The sample was randomly divided into experimental and waiting-list control groups. The experimental intervention provided AIDS risk education, cognitive-behavioral self-management training, sexual assertion training, and attention to the development of steady and self-affirming social supports. Experimental group participants greatly reduced their frequency of high-risk sexual practices and increased behavioral skills for refusing sexual coercions, AIDS risk knowledge, and adoption of "safer sex" practices. Change was maintained at the 8-month follow-up. PMID- 2925975 TI - Two types of delinquents and their institutional adjustment. AB - This research tested a typology classifying 326 incarcerated delinquent boys as buoyant or beset, depending on their level of anxiety and depression at intake. Findings reveal that the two types of boys differed in some aspects of life history and personality, that the buoyant type adjusted better to the institution's group-oriented treatment program, and that buoyant and beset boys responded differentially to some components of the treatment. Implications are drawn regarding the usefulness of the typology for guiding differential treatment. PMID- 2925976 TI - Differences between more and less effective psychotherapists: a study of select therapist variables. AB - This study examined differences between more and less effective trainee psychotherapists. Therapists were assigned to one of two groups depending on whether the preponderance of their patients' changes in symptomatology indicated more or less improvement over the course of therapy. Therapist variables included emotional adjustment, relationship skills, eliciting patient involvement, credibility, directiveness, and theoretical orientation. Less effective therapists were revealed to have lower levels of empathic understanding, to rate their patients as more involved in treatment, and to rate themselves as more supportive than the more effective therapists. Less effective therapists also valued comfort and stimulation significantly more and valued intellectual goals significantly less than did more effective therapists. PMID- 2925977 TI - Changes in food intake and activity after quitting smoking. AB - Quitting smoking often results in weight gain. The causes of the gain are not known. The present study evaluated changes in calories, total sugars, sucrose, fat, protein, and nonsugar carbohydrates as well as changes in activity levels after quitting smoking. Ninety-five subjects were randomly assigned to either early (Week 2) or late (Week 6) quit dates. Subjects were assessed on weight, food intake, activity levels, and smoking levels at baseline, at Weeks 4 and 8, and at Weeks 12 and 26 postquit. The results indicated significant increases in calories, sucrose, and fats 2 weeks after the quit date. Changes for total sugars were less consistent. Activity levels did not change significantly. Early caloric increases predicted weight gain at 26 weeks for abstinent women. No relation was found for abstinent men, but interpretation of this finding is weakened by a small subsample size. Abstinent subjects gained over 9 lb by 26 weeks postquit. Despite this gain, Week 26 results showed that caloric intake for abstinent women was approximately equal to that observed at baseline, whereas that for abstinent men had dropped significantly. PMID- 2925978 TI - Nicotine replacement: effects of postcessation weight gain. AB - The present study examined nicotine replacement effects on postcessation weight gain in smoking cessation clinic volunteers using objective indices of cigarette smoking, gum use, and body weight. After they achieved abstinence, subjects were randomly assigned to either active nicotine or placebo gum conditions for 10 weeks, during which smoking status was carefully monitored. Analyses revealed strong evidence for a gum effect on weight gain, with active gum users gaining a mean total of 3.8 lb compared with 7.8 lb for placebo gum users at the end of the 10-week trial. Evidence for a dose-response relation was found, suggesting that more gum use (greater than or equal to 6.5 pieces/day) resulted in greater weight suppression. Placebo gum subjects reported greater postcessation increases in eating and hunger compared with active gum subjects. The implications of the weight suppression effect of nicotine gum for smoking cessation treatments are discussed. PMID- 2925979 TI - Using alcohol expectancies to predict adolescent drinking behavior after one year. AB - An accumulating literature has shown the influence of childhood experiences associated with alcohol use on later drinking practices. Recent studies have suggested that alcohol-related expectancy may serve as an intervening variable to connect these early experiences with the later, proximal decision to drink when opportunities for actual alcohol consumption arise. Those studies, however, have collected expectancy and drinking data concurrently, whereas the present study for the first time reports on the power of expectancies measured in early adolescents (seventh and eighth grades) to predict self-reported drinking onset and drinking behavior measured a full year later. Results show that five of seven expectancy scores readily discriminated between nonproblem drinkers and those subsequently beginning problem drinking and accounted for a large portion of the variance in a continuous quantity/frequency index and a problem drinking index. The strength of these timelagged relations strengthens the case for inferring that expectancies have causal power on drinking behavior and suggests prevention strategies. PMID- 2925980 TI - Monopolar and bipolar treatment. AB - Monopolar and bipolar electrosurgical treatments are markedly different in principle, but the terms are often confused. The following article explains the differences between these two popular modalities. PMID- 2925981 TI - Granuloma pyogenicum (pregnancy tumor). PMID- 2925982 TI - Benefits of the CO2 laser for verruca resistant to other modalities of treatment. AB - The benefits of the carbon dioxide (CO2) laser in the treatment of verruca resistant to other forms of treatment have been studied. Twenty-five patients with warts unsuccessfully treated from one to five times previously were treated with the laser, followed for a minimum of 6 months, and evaluated. Eight of these patients (32%) gained a total permanent cure. An additional five treatments resulted in a subtotal (over 75%) cure but some warts remained. Thus, 13 of 25 patients (52%) experienced complete or partially successful treatment. The CO2 laser is a valuable modality in the treatment of recalcitrant warts but cannot be expected to cure all such warts. PMID- 2925983 TI - Donor island harvesting for micro- and minigrafting. AB - Donor island harvesting, a method of obtaining micro- and minigrafts from the hair-bearing strip between donor rows, is described. PMID- 2925984 TI - The precision binocular loupe. AB - The binocular loupe has long been used by dermatologists to improve their visualization of skin disease and for fine surgical work. As more and more dermatologists perform sclerotherapy and laser surgery, the popularity of magnifying loupes will increase. PMID- 2925985 TI - Evaluating the efficacy of the punch hair grafting technique. AB - The author evaluates the efficacy of the punch hair grafting technique by measuring hair density and the number of terminal hairs that should grow in a graft. PMID- 2925986 TI - The association of lichen planus of the penis with squamous cell carcinoma in situ and with verrucous squamous carcinoma. AB - Two cases of squamous cell carcinoma (SCC) of the penis, one verrucous type and one in situ, arising in association with an inflammatory dermatosis most consistent with lichen planus, are described. Although SCC has previously been reported to have arisen from lichen planus of the oral mucosa, these are the first reported cases of the coexistence of these processes on the penis. PMID- 2925987 TI - Carbon dioxide laser blepharoplasty: conjunctival temperature during surgery. AB - Eight patients underwent carbon dioxide (CO2) laser blepharoplasty. The temperature of the upper eyelid conjunctiva was monitored and recorded during laser surgery. A minimal increase in temperature was noted. This study confirms the absence of thermal injury at a distal site from the laser application and the safety of the laser procedure. PMID- 2925988 TI - Mohs surgery is the treatment of choice for recurrent (previously treated) basal cell carcinoma. AB - We reviewed all studies (since 1945) reporting recurrence rates for treatment of recurrent (previously treated) basal cell carcinomas (BCC) using surgical excision, radiotherapy, cryotherapy, curettage and electrodesiccation, and Mohs micrographic surgery. The 5-year recurrence rate for Mohs micrographic surgery is 5.6%. The recurrence rate for non-Mohs modalities of 19.9% is nearly four times higher. Individual recurrence rates for the non-Mohs modalities are 17.4% for surgical excision, 40.0% for curettage and electrodesiccation, and 9.8% for radiation therapy. There are no studies reporting 5-year data for cryotherapy. However, the recurrence rate is 13.0% for cryotherapy when the follow-up period is less than five years. The data support the following conclusions: (1) Mohs surgery is the treatment of choice for recurrent BCC; (2) if the patient is not a surgical candidate and the lesion is small, radiation therapy is an alternative that offers a better chance for cure than the other non-Mohs modalities; and (3) curettage and electrodesiccation should not be used to treat recurrent basal cell carcinoma. PMID- 2925989 TI - Postoperative Trichosporon beigelii soft tissue infection. AB - A case of postsurgical cutaneous infection with Trichosporon beigelii in an apparently immunocompetent individual is reported. This is a rare surgical complication and the first report of localized skin infection by this organism postoperatively. PMID- 2925990 TI - False-negative margins. PMID- 2925991 TI - Comparison between in vivo and in vitro cutaneous penetration of fenvalerate in tobacco budworm (Lepidoptera: Noctuidae). AB - In vivo and in vitro penetration of fenvalerate were compared in the 3-d-old fifth-instar tobacco budworm, Heliothis virescens (F). In the in vitro studies, a piece of cuticle was excised and mounted on a diffusion cell, and the amount of radioactivity present in the cuticle and medium was determined at various time intervals. At 24 h, approximately 7.4% of the dose was located in the cuticle, whereas only 1.6% actually penetrated. In the in vivo studies, approximately 7.4% of the radioactivity was recovered from the body after cuticular wash. PMID- 2925992 TI - Inhibition of growth and development of tobacco hornworm (Lepidoptera: Sphingidae) larvae by cyromazine. AB - When fed to larvae of tobacco hornworm, Manduca sexta (L.), cyromazine strongly inhibited normal growth and development. Depending on the dose or period of feeding, symptoms were cuticular melanization, swellings in intersegmental regions, cuticular lesions, rupture of the body wall, and death. At greater than 10 ppm, cyromazine in the diet initiated symptoms in fifth instars, whereas greater than 20 ppm induced symptoms which led to death during the instar or at molting. The ratio of chitin to larval body weight in both cyromazine-exposed and control fifth instars increased slightly from ecdysis to 42 h. However, this ratio did not differ between the two groups, indicating that cyromazine had no immediate or direct effect on chitin production. When cyromazine was ingested by fifth instars, it was excreted rapidly, and a small amount (less than 5%) was metabolized to melamine. The amount of cyromazine found in the hemolymph remained relatively constant during the feeding period, whereas the amount present in the body wall increased with time and was localized in the KOH-soluble fraction. Cyromazine may inhibit growth or expansion of the body wall (or both) sufficiently to prevent normal internal growth, producing the observed symptoms and leading to abnormal development. PMID- 2925993 TI - The effect of traffic noise on sleep of young adults in their homes. AB - The disturbance of sleep by traffic noise is a major problem area in noise pollution. Extensive laboratory tests using multichannel electroencephalograms (EEG) have been carried out by many workers to determine the general response of people when exposed to noise during sleep. An experimental technique for obtaining results in people's homes has been developed using a simplified one channel EEG. The responses of six people in the age range 19-24 were measured. A significant correlation was found between sleep disturbance and traffic noise when the noise is expressed in EPNdB. In the home experiments the subjects appeared to be approximately 10 dB less sensitive to noises than laboratory subjects for similar noise exposure. There also appeared to be some adaptation to the noise exposure; however, only one subject was tested for a period of 20 days and was insufficient to give definite results on adaptation. PMID- 2925994 TI - Interaural cross-correlation coefficients in stereo-reproduced sound fields. AB - Interaural cross-correlation coefficients (ICCCs) were measured in stereo reproduced fields where a KEMAR (Knowles electric manikin for acoustic research) was located. These ICCCs were then compared with those in an ideal, diffuse sound field. The ICCCs in a reverberant field are not reproduced accurately using a conventional two-channel stereo-reproduction technique. In four-channel stereo reproduction, however, the ICCCs can, for the most part, be reproduced accurately as in an ideal, diffuse sound field. Some experimental results are also shown for binaural discrimination of the ICCCs. PMID- 2925995 TI - Nonlinear and active two-dimensional cochlear models: time-domain solution. AB - A numerical solution method for two-dimensional (2-D) cochlear models in the time domain is presented. The method has particularly been designed for models with a cochlear partition having nonlinear and active mechanical properties. The 2-D cochlear model equations are reformulated as an integral equation for the acceleration of the basilar membrane (BM). This integral equation is discretized with respect to the spatial variable to yield a system of ordinary differential equations in the time variable. To solve this system, the variable step-size, fourth-order Runge-Kutta method described in Diependaal et al. [J. Acoust. Soc. Am. 82, 1655-1666 (1987)] is used. This method is robust and computationally efficient. The incorporation of a simple middle-ear model can be handled by this method. The method can also be extended to models in which the cochlear partition at each point along its length is represented by more than one degree of freedom. PMID- 2925996 TI - Pitch identification of simultaneous diotic and dichotic two-tone complexes. AB - This study examines subjects' ability to recognize the pitches of two missing fundamentals in two simultaneous two-tone complexes whose partials are distributed in various ways between subjects' ears. The data show that identification performance is affected on different levels. Limited frequency resolution in the peripheral auditory system can degrade performance, but only if none of the four stimulus partials is aurally resolved. Identification performance is only weakly dependent on the manner of distributing partials between the ears. In some cases it was found that, probably at a very central level (e.g., attention), the identification processes of both simultaneous pitches interfere with one another. Some subjects are more likely to identify the pitch of one two-tone complex when the harmonic order of the other complex is higher than when this harmonic order is lower. Finally, some subjects tend to hear the complex tones analytically, i.e., perceive pitches of single partials instead of the missing fundamentals for some distribution of partials between the ears. PMID- 2925997 TI - Detection and discrimination of spectral peaks and notches at 1 and 8 kHz. AB - The ability of subjects to detect and discriminate spectral peaks and notches in noise stimuli was determined for center frequencies fc of 1 and 8 kHz. The signals were delivered using an insert earphone designed to produce a flat frequency response at the eardrum for frequencies up to 14 kHz. In experiment I, subjects were required to distinguish a broadband reference noise with a flat spectrum from a noise with either a peak or a notch at fc. The threshold peak height or notch depth was determined as a function of bandwidth of the peak or notch (0.125, 0.25, or 0.5 times fc). Thresholds increased with decreasing bandwidth, particularly for the notches. In experiment II, subjects were required to detect an increase in the height of a spectral peak or a decrease in the depth of a notch as a function of bandwidth. Performance was worse for notches than for peaks, particularly at narrow bandwidths. For both experiments I and II, randomizing (roving) the overall level of the stimuli had little effect at 1 kHz, but tended to impair performance at 8 kHz, particularly for notches. Experiments III-VI measured thresholds for detecting changes in center frequency of sinusoids, bands of noise, and spectral peaks or notches in a broadband background. Thresholds were lowest for the sinusoids and highest for the peaks and notches. The width of the bands, peaks, or notches had only a small effect on thresholds. For the notches at 8 kHz, thresholds for detecting glides in center frequency were lower than thresholds for detecting a difference in center frequency between two steady sounds. Randomizing the overall level of the stimuli made frequency discrimination of the sinusoids worse, but had little or no effect for the noise stimuli. In all six experiments, performance was generally worse at 8 kHz than at 1 kHz. The results are discussed in terms of their implications for the detectability of spectral cues introduced by the pinnae. PMID- 2925998 TI - Categorical perception of conspecific communication sounds by Japanese macaques, Macaca fuscata. AB - Field studies indicate that Japanese macaque (Macaca fuscata) communication signals vary with the social situation in which they occur [S. Green, "Variation of vocal pattern with social situation in the Japanese monkey (Macaca fuscata): A field study," in Primate Behavior, edited by L. A. Rosenblum (Academic, New York, 1975), Vol. 4]. A significant acoustic property of the contact calls produced by these primates is the temporal position of a frequency peak within the vocalization, that is, an inflection from rising to falling frequency [May et al., "Significant features of Japanese macaque communication sounds: A psychophysical study," Anim. Behav. 36, 1432-1444 (1988)]. The experiments reported here are based on the hypothesis that Japanese macaques derive meaning from this temporally graded feature by parceling the acoustic variation inherent in natural contact calls into two functional categories, and thus exhibit behavior that is analogous to the categorical perception of speech sounds by humans. To test this hypothesis, Japanese macaques were trained to classify natural contact calls by performing operant responses that signified either an early or late frequency peak position. Then, the subjects were tested in a series of experiments that required them to generalize this behavior to synthetic calls representing a continuum of peak positions. Demonstration of the classical perceptual effects noted for human listeners suggests that categorical perception reflects a principle of auditory information processing that influences the perception of sounds in the communication systems not only of humans, but of animals as well. PMID- 2925999 TI - Across-critical-band processing of amplitude-modulated tones. AB - Two experiments using two-tone sinusoidally amplitude-modulated stimuli were conducted to assess cross-channel effects in processing low-frequency amplitude modulation. In experiment I, listeners were asked to discriminate between two sets of two-tone amplitude-modulated complexes. In one set, the modulation phase of the lower frequency carrier tone was different from that of the upper frequency carrier tone. In the other stimulus set, both amplitude-modulated carriers had the same modulator phase. The amount of phase shift required to discriminate between the two stimulus sets was determined as a function of the separation between the two carriers, modulation depth, and modulation frequency. Listeners could discriminate a 50 degrees-60 degrees phase shift between the modulated envelopes for tones separated by more than a critical band. In experiment II, the modulation depth required to detect modulation of a probe carrier was measured in the presence of an amplitude-modulated masker. The threshold for detecting probe modulation was determined as a function of the separation between the masker and probe carriers, the phase difference between the masker and probe modulators, and masker modulation depth (in all conditions, the rate of probe and masker modulation was 10 Hz). The threshold for detecting probe modulation was raised substantially when the masker tone was also modulated. The results are consistent with theories suggesting that amplitude modulation helps form auditory objects from complex sound fields. PMID- 2926000 TI - Headphone simulation of free-field listening. I: Stimulus synthesis. AB - This article describes techniques used to synthesize headphone-presented stimuli that simulate the ear-canal waveforms produced by free-field sources. The stimulus synthesis techniques involve measurement of each subject's free-field-to eardrum transfer functions for sources at a large number of locations in free field, and measurement of headphone-to-eardrum transfer functions with the subject wearing headphones. Digital filters are then constructed from the transfer function measurements, and stimuli are passed through these digital filters. Transfer function data from ten subjects and 144 source positions are described in this article, along with estimates of the various sources of error in the measurements. The free-field-to-eardrum transfer function data are consistent with comparable data reported elsewhere in the literature. A comparison of ear-canal waveforms produced by free-field sources with ear-canal waveforms produced by headphone-presented simulations shows that the simulations duplicate free-field waveforms within a few dB of magnitude and a few degrees of phase at frequencies up to 14 kHz. PMID- 2926001 TI - Headphone simulation of free-field listening. II: Psychophysical validation. AB - Listeners reported the apparent spatial positions of wideband noise bursts that were presented either by loudspeakers in free field or by headphones. The headphone stimuli were digitally processed with the aim of duplicating, at a listener's eardrums, the waveforms that were produced by the free-field stimuli. The processing algorithms were based on each subject's free-field-to-eardrum transfer functions that had been measured at 144 free-field source locations. The headphone stimuli were localized by eight subjects in virtually the same positions as the corresponding free-field stimuli. However, with headphone stimuli, there were more front-back confusions, and source elevation seemed slightly less well defined. One subject's difficulty with elevation judgments, which was observed both with free-field and with headphone stimuli, was traced to distorted features of the free-field-to-eardrum transfer function. PMID- 2926002 TI - High-frequency audiometry: test reliability and procedural considerations. AB - This study compared the reliability of a recently developed high-frequency audiometer (HFA) [Stevens et al., J. Acoust. Soc. Am. 81, 470-484 (1987)] with a less complicated system that uses supraaural earphones (Koss system). The new approach permits calibration on an individual basis, making it possible to express thresholds at high frequencies in dB SPL. Data obtained from 50 normal hearing subjects, ranging in age from 10-60 years, were used to evaluate the effects on reliability of threshold variance, earpiece/earphone fitting variance, and the variance associated with the HFA calibration process. Without earpiece/earphone replacement, the reliability of thresholds for the two systems is similar. With replacement, the HFA showed poorer reliability than the Koss system above 11 kHz, largely due to errors in estimating the calibration function. HFA reliability is greater for subjects with valid calibration functions over the entire frequency range. When average correction factors are applied to the Koss data in an effort to convert threshold estimates to dB SPL, individual transfer functions are not represented accurately. Thus the benefit of being able to express thresholds at high frequencies in dB SPL must be weighed against the additional source of variability introduced by the HFA calibration process. PMID- 2926003 TI - Fundamental frequency modulation of the human voice by the heartbeat: preliminary results and possible mechanisms. AB - Signal-averaging techniques reveal that the vocal fundamental frequency (F0) of a sustained vowel is modulated over a period equal to that of the speaker's heart cycle. Average F0 deviation varies in an orderly way from about 0.5% to about 1.0% as F0 changes. Location of the peak deviation in the time frame of the heart cycle also changes systematically with vocal F0. Modulation of the vocal F0 is likely to be caused by pressure-related changes in the stiffness of the vascular bed of the vocal folds and by alterations of the geometry of the thyroarytenoid muscle produced by periodic vascular engorgement. PMID- 2926004 TI - Inhibiting the Lombard effect. AB - The Lombard effect is the tendency to increase one's vocal intensity in noise. The present study reports three experiments that test the robustness of the Lombard effect when speakers are given instructions and training with visual feedback to help suppress it. The Lombard effect was found to be extremely stable and robust. Instructions alone had little influence on the response to the noise among untrained speakers. When visual feedback correlated with vocal intensity was presented, however, subjects could inhibit the Lombard response. Furthermore, the inhibition remained after the visual feedback was removed. The data are interpreted as indicating that the Lombard response is largely automatic and not ordinarily under volitional control. When subjects do learn to suppress the effect, they seem to do so by changing overall vocal level rather than their specific response to the noise. PMID- 2926005 TI - On the relation between subglottal pressure and fundamental frequency in phonation. AB - The change in fundamental frequency with subglottal pressure in phonation is quantified on the basis of the ratio between vibrational amplitude and vocal fold length. This ratio is typically very small in stringed instruments, but becomes quite appreciable in vocal fold vibration. Tension in vocal fold tissues is, therefore, not constant over the vibratory cycle, and a dynamic tension gives rise to amplitude-frequency dependence. It is shown that the typical 2-6 Hz/cm H2O rise in fundamental frequency with subglottal pressure observed in human and canine larynges is a direct and predictable consequence of this amplitude frequency dependence. Results are presently limited to phonation in the chest register. PMID- 2926006 TI - Acoustic-phonetic characteristics of speech produced in noise and while wearing an oxygen mask. AB - The present study investigated changes in the prosodic and acoustic-phonetic features of isolated words by four male talkers speaking in quite and in pink noise at a level of 95 dB SPL. Speech samples were collected both with and without an oxygen mask. Changes in duration, fundamental frequency, total energy, and formant center frequency were analyzed. In addition to the expected changes of increased pitch and amplitude associated with speaking in noise without an oxygen mask, significant effects were found (particularly in the formant center frequencies) as a result of using the oxygen mask. When the oxygen mask was employed, no further significant changes were caused by adding noise to the speaking situation. PMID- 2926007 TI - Long-term memory for unfamiliar voices. AB - From a sample of young male Californians, ten speakers were selected whose voices were approximately normally distributed with respect to the "easy-to-remember" versus "hard-to-remember" judgments of a group of raters. A separate group of listeners each heard one of the voices, and, after delays of 1, 2, or 4 weeks, tried to identify the voice they had heard, using an open-set, independent judgment task. Distributions of the results did not differ from the distributions expected under the hypothesis of independent judgments. For both "heard previously" and "not heard previously" responses, there was a trend toward increasing accuracy as a function of increasing listener certainty. Overall, heard previously responses were less accurate than not heard previously responses. For heard previously responses, there was a trend toward decreasing accuracy as a function of delay between hearing a voice and trying to identify it. Information-theoretic analysis showed loss of information as a function of delay and provided means to quantify the effects of patterns of voice confusability. Signal-detection analysis revealed the similarity of results from diverse experimental paradigms. A "prototype" model is advanced to explain the fact that certain voices are preferentially selected as having been heard previously. The model also unites several previously unconnected findings in the literature on voice recognition and makes testable predictions. PMID- 2926009 TI - An interpretation of cortical maps in echolocating bats. AB - Target parameters such as reflectivity, range, velocity, and angular position are represented by ordered maps of tuned cortical neurons in insectivorous bats. It is suggested that the response of each neuron in such a map is determined by a hypothesis test conditioned on a particular value of the mapped parameter. The excitation of each neuron is then interpreted as a sample value of a conditional log-likelihood ratio or a log-likelihood function. Interpolation between the samples, which is needed to find the parameter that maximizes the mapped function (e.g., the maximum likelihood parameter estimate), can be accomplished with overlapped tuning curves. An attempt to portray a sharp peak by a weighted sum of relatively broad neuronal tuning curves or interpolation functions results in excitatory center/inhibitory surround behavior. Facilitation or antifacilitation of neurons that are likely to be excited by succeeding observations can be used for sequential detection and tracking. Interpolation and pulse-to-pulse data storage capability are required to explain range jitter sensitivity and to allow for moving target indication in bat sonar. If a cortical map represents an ordered array of hypothesis tests, then many such tests are implemented in parallel when target parameters are unknown. Detection performance is then degraded relative to the idealized situation in which all parameters are specified. Performance in noise may thus appear to be much worse than that of an ideal detector, even if each hypothesis test is optimally implemented. PMID- 2926008 TI - Speech perception in children with histories of recurrent otitis media. AB - The present study investigated the ability of 5-year-old children to perceive differences in voice onset time (VOT) in naturally produced speech. Three groups of children whose hearing was within normal limits at the time of the experiment were tested on identification and discrimination tasks: (1) group C, in which the children had normal language abilities and no history of severe, recurrent otitis media (OM), (2) group OM, in which the children had histories of severe, recurrent OM but normal language abilities, and (3) group OM/DL, in which the children had histories of severe OM and delays in the acquisition of linguistic competence. Compared to group C, group OM/DL showed marked differences in their ability to identify and discriminate speech patterns. Their perception was less categorical, as well, in that there was less of a peak in the discrimination function at the region of the phoneme boundary. The performance of group OM fell between the other two groups, with deficits being more pronounced in the discrimination task than in the identification task. The results supported the idea that episodes of OM can produce periods of sensory deprivation that alter perceptual abilities. The relation of a history of OM to later language and academic difficulties was also considered. PMID- 2926010 TI - Ubiquity of hyperacuity. AB - A decision as to whether two line segments are colinear, as on a vernier scale (- /-- vs --/--), can be made with high sensitivity by the human visual system. Just noticeable vernier displacement is much smaller than the separation required to resolve two parallel lines, i.e., to perceive them as two lines rather than one. Vernier acuity is thus also called "hyperacuity." Similar effects have been discovered in bat echolocation, for discrimination of a range-jittered point target from a nonjittered target, in the jamming avoidance response (JAR) of electric fish, and in differential pitch sensitivity experiments with human subjects. Are jitter sensitivity in echolocation, JAR in electroreception, differential pitch sensitivity in audition, and vernier acuity in vision based on the same general principle? The results in this article indicate that such phenomena are indeed similar from the viewpoint of detection theory, and that experimental performance can be used to behaviorally estimate auditory parameters such as bandwidth, beamwidth, and temporal resolution, as well as to test different signal processing models without resort to masking. Applications of the hyperacuity effect to radar, sonar, and medical ultrasound are suggested. PMID- 2926011 TI - The development of a practising nursing faculty. AB - Practice is where skills are developed and where theory must pass testing. This is best done by observing and responding to human needs so that theory generated will have a precise fit. A variety of joint appointments with a focus on nursing have been established between the Faculty of Nursing at The University of Calgary and nursing service agencies in Calgary, Alberta, Canada. The expected outcome is congruence between teaching, theory development, and practice. This paper differentiates faculty practice as scholarship from other forms of faculty involvement in practice settings. The nature of faculty practice is examined and various models of faculty practice are discussed. The Calgary model, designed to fit faculty member's focus on care to specific practice settings is described. PMID- 2926012 TI - Bulimic and non-bulimic college females' perceptions of family adaptability and family cohesion. AB - Bulimia appears to be increasing among young women of middle to upper socioeconomic status. Although the aetiology of bulimia syndrome is not fully understood, family functioning patterns are thought to contribute to development of the disorder. The purpose of this study was to investigate the relationship between self-reported bulimic behaviour in female college students and their perceptions of family adaptation and family cohesion levels. A sample of 308 subjects from three social sororities at the University of Missouri-Columbia completed a demographic questionnaire, the Bulimic Test (BULIT) and the Family Cohesion and Adaptability Evaluation Scale (FACES III). Twenty subjects were found to be bulimic, 21 incipient, and 267 non-bulimic. Analysis of data using the chi-square test resulted in a statistically significant relationship between self-reported bulimia and perceptions of family cohesion. No significant relationship was found between self-reported bulimia and family adaptation. Implications for nursing practice are discussed. PMID- 2926013 TI - Attitudes and behaviours of nurses towards the elderly in an acute care setting. AB - The study was designed to determine the attitudes of health care workers towards the elderly in acute care settings and to investigate variations in types of interaction between staff and elderly patients. A questionnaire and Kogan's Old People Scale were used together with direct non-participant observation of nurse patient interaction. The questionnaire was completed by 50 registered nurses, 20 nursing aides, four degree nurses and eight volunteers. Of the four groups, the volunteers showed the most favourable attitudes, the registered nurses and degree nurses were virtually tied and the nursing aides were lower in the rating. Staff who expressed a preference for working in geriatrics and rehabilitation had a high correlation on the Kogan's Old People Scale: (r(77) = 0.38, P less than 0.01) and (r(77) = 0.32, P less than 0.01) respectively. It was also found that those who rated basic care as lower in importance to patient well-being than, for example, talking to patients, were more positive than were those who rated basic care higher in importance. In the second data collection, 47 female patients (mean age = 67.4 years) and 43 male patients (mean age = 71.5 years) were observed. It was found that 74% of patients spent almost 95% of their time inactively, either in bed or sitting in a chair. Neither age nor mental alertness relates to activity level, but mental alertness was found to be related to engaging in constructive activities. During the observation periods 41% of the patients did not interact with staff.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2926014 TI - Community psychiatric nurses: their self-perceived roles. AB - The self-perceived role of 16 community psychiatric nurses (CPNs) were analysed with reference to four conceptual models of psychiatric illness. The roles discussed by the CPNs echoed many of those found in previous research. Overall the CPNs used different models of illness when discussing various aspects of their roles. It is believed that the models of illness preferred by CPNs may be a useful reflection of the role they may have in caring for different client groups. PMID- 2926015 TI - Theory development in perspective: the role of conceptual frameworks and models in theory development. AB - An analysis of most scientific theories reveals the presence of a variety of components which function as constitutive elements of theories. Wider cultural paradigms often influence the construction and content of theories in a decisive way. Analogies between incongruent domains provide significant points of departure for the development of models which are often metaphoric in nature. Different metaphors provide alternative conceptual frameworks in terms of which it is possible to describe and explain nursing phenomena. Scientific theories that are developed on the basis of such metaphorical models are limited in their explanatory capacity. When the intrinsic limitations of such scientific models are not recognized, they often lead to distorted, one-sided and reductionistic explanations of phenomena. Metaphysical assumptions concerning the nature of human beings, illness, health, etc., are also of decisive significance in this process, e.g. mechanistic models based on a naturalistic view of man lead theorizing astray. These theses are illustrated with reference to behavioral systems theory as developed by Dorothy Rogers. PMID- 2926016 TI - Education and support for the newly diagnosed cardiac family: a vital link in rehabilitation. AB - In eastern Canadian small cities, community programming for cardiac rehabilitation is in its infancy. As professional awareness of the special needs of cardiac clients has grown, some components of cardiac rehabilitation programmes have developed, albeit autonomously from one another, e.g. in-hospital education, home visiting, exercise programmes, and support groups. Attempts are being made to establish communication channels among the health personnel involved in the different agencies in order to achieve a better availability and coordination of services for the benefit of cardiac clients and their families. To address needs arising after the first hospitalization or first diagnosis of cardiac disease, an education and support programme has been established by a university nursing faculty through the efforts of its junior students. This programme takes the form of 8-week series of informal classes. Objectives, methods and outcomes are outlined. Some recommendations for future community cardiac rehabilitation efforts emerge from clinical practice and programme evaluation. Implications for health professionals in such future activities are discussed. PMID- 2926017 TI - A survey of the attitudes of senior nurses towards graduate nurses. AB - This small scale survey is one aspect of a larger study of the progress and function of graduates of a nursing degree course. There is very little current literature regarding the views of senior nurses on the role and function of graduate nurses. The aim of this study was not to survey all senior nurses, but to obtain the views of senior nurses in the areas where graduates included in the main study were working. A descriptive survey approach was taken using postal questionnaires to ascertain views on the role and function of graduate nurses. Six chief nurses and 11 directors of nursing and midwifery services returned the questionnaires. The results showed varied views on whether graduates should and do function differently to traditionally trained nurses and interesting comments were made in relation to this. The implications of the study are important, since the views of senior nurses are likely to influence the posts held by graduates and the way they function within those posts, and there is a need for a more in depth study of this area. PMID- 2926019 TI - Sex differences in school-aged children with pervasive attention deficit hyperactivity disorder. AB - This study investigated 54 children (37 boys and 17 girls) with cross-situational attention deficit hyperactivity disorder (ADHD) to determine whether there are sex differences in the expression of either the primary or secondary symptomatology of ADHD. Results indicated that the male and female ADHD groups were strikingly similar on all measures of primary (impulsivity, inattention, and overactivity) and secondary (learning problems, externalizing symptoms, internalizing symptoms, peer relationship difficulties, and self-perceptions) symptomatology included in this study. The lack of significant sex differences conflicts with prior reports in the literature, and these conflicting results are discussed in terms of differences in inclusion criteria. Implications for understanding the long-term outcome of ADHD in girls are also discussed. PMID- 2926018 TI - Depressive characteristics of physically abused children. AB - Physically abused and nonabused children were compared on child-completed measures of depression, hopelessness, self-esteem, and locus of control. Results indicated that, in comparison with nonabused controls, abused children evidenced more depressive symptoms, heightened externality, lower self-esteem, and greater hopelessness about the future. Group differences in depressive symptomatology were not accounted for on the basis of differences in age, sex, race, gender, IQ, or socioeconomic status. Results replicate the results of Kazdin, Moser, Colbus, and Bell (1985) derived from a sample of physically abused psychiatric inpatients and extend the generality of these findings to abused children of nonpatient status. Implications of the findings for clinical interventions, theoretical models of child depression, and future research are discussed. PMID- 2926020 TI - Validation of the reasons for living inventory in general and delinquent adolescent samples. AB - Two studies are reported that discuss the validation of an adult suicide prediction questionnaire for use with adolescents. The Reasons for Living Inventory (RFL; Linehan, Goodstein, Nielsen, & Chiles, 1983) was slightly modified and administered to two samples of adolescents: one from a general high school population and one from a population of juvenile delinquents receiving psychological treatment in a correctional facility. As with adults, adolescents who reported more reasons for staying alive were less apt to report past or recent suicidal thoughts or behaviors. Evidence of convergent validity emerged via correlations of RFL subscales with depression, hopelessness, and other suicide inventories. Evidence of discriminant validity emerged in that correlations with social desirability were not large. Evidence of construct validity emerged in that the RFL subscales related to suicidal thoughts and behaviors over and above depression and hopelessness. Differences between general and delinquent adolescents' reasons for living are discussed. PMID- 2926022 TI - A comparison of 13-year-old boys with attention deficit and/or reading disorder on neuropsychological measures. AB - This study compared 13-year-old boys with attention deficit disorder (ADD) and/or reading disability (RD), and controls with neither disorder on a battery of verbal and nonverbal neuropsychological measures. The aim was to examine whether ADD was associated with a qualitatively distinct pattern of deficits compared with RD. None of the measures differentiated the boys with ADD-only from the controls; the only deficit associated with ADD was slightly lower IQ. RD, on the other hand, was associated with deficits in memory and verbal skills. PMID- 2926021 TI - Social-cognitive processing and depressive symptoms in children: a comparison of measures. AB - We assessed aspects of the reliability and validity of three measures of social cognitive processing in children that have been developed to investigate the relations of such processes to childhood depression: the Children's Attributional Style Questionnaire (CASQ), the Children's Negative Cognitive Error Questionnaire (CNCEQ), and the Common Beliefs Inventory for Students (CBIS). In an unselected sample of 61 children, aged 8 to 12, the internal consistencies of the total scores on the CNCEQ and the CBIS were good; for the CASQ, it was only moderate. Internal consistencies of all subscale scores were inadequate. Despite this, several subscale and total scores were significantly associated with depressive symptoms, and the measures were generally correlated with each other. Although these data are encouraging concerning the role of social-cognitive processing in childhood depression, the field needs to develop psychometrically stronger measures and to test the role of social cognition in prospective studies of depression. PMID- 2926023 TI - The structure and correlates of self-reported symptoms in 11-year-old children. AB - Self-reports of DSM-III symptomatology were obtained from 792 11-year-old children using the Diagnostic Interview Schedule for Children (DISC). We report results concerning 13 subscales derived from the DISC. Factor analysis of the subscales suggested a broad distinction between "externalizing" and "internalizing" disorder for boys' self-report. For girls, two separate internalizing factors representing anxiety and depression emerged. We also found sex differences in correlates of self-reported disorder. Finally, we examined agreement between child and parent and teacher reports. Overall, agreement was relatively low, although somewhat higher for child-parent than for child-teacher. PMID- 2926024 TI - The effects of background illumination and stimulant medication on smooth pursuit eye movements of hyperactive children. AB - Problems with visual information processing have been reported in children with the diagnosis of attention deficit disorder with hyperactivity (ADD H), and deficits in oculomotor control have been posited as an important factor in this phenomenon. To assess aspects of oculomotor performance, smooth pursuit eye movements (PEMs) were recorded electrooculographically in 20 ADD H and 20 age matched control children and computer-analyzed for discrete (velocity arrests) and global (root mean square error) disruptions. The effects of stimulant medication (methylphenidate), together with manipulations designed to influence behavioral (attention) and physiological (cerebellar) processes involved in PEM performance, were examined. The tracking patterns of nonmedicated ADD H children contained significantly more discrete aberrations on baseline conditions. Although no single experimental manipulation significantly improved tracking performance in ADD H children, combining all experimental conditions did normalize PEMs in these subjects. Slight improvements in PEM performance in association with medication correlated positively with dose of medication and with medication-related improvements in behavior. In light of these data, arguments are presented in support of (a) hypoarousal as a contributing factor underlying oculomotor difficulties in ADD H children, and (b) subcortical involvement in PEM dysfunction. PMID- 2926025 TI - Screening for hypercholesterolemia in college students. AB - Two national panels have recommended similar, specific strategies for detecting hypercholesterolemia: selective screening for children aged 2 to 19, and mass screening for individuals aged 20 and over. It is, however, unclear how best to apply these recommendations to a college student population. In order to determine which strategy is more efficient, this study compared mass with selective screening of college students for hypercholesterolemia. In the mass screening strategy, all entering students were asked to have their cholesterol levels measured and to provide other coronary risk factor information. In the selective screening strategy, all sophomores with a family history of heart disease were asked to participate in a risk factor screening program. In this study, mass screening identified more hypercholesterolemic students with less effort per case found than did selective screening. We recommend that college health practitioners consider mass screening programs to identify students who could benefit from coronary risk reduction. PMID- 2926026 TI - Sex and the 1980s college student. PMID- 2926028 TI - American College Health Association standards on student health insurance. January 1988. Task Force on Student Health Insurance. PMID- 2926029 TI - Is Lyme disease a health threat for your students? PMID- 2926027 TI - Self-care practices of college students. AB - The literature indicates that the majority of symptoms of minor illness or injury experienced by individuals are handled routinely through some form of self-care. Less well described are the sources of information relied on in the self-care decision-making process. The purpose of this study was to assess the use of self care measures by college students prior to visiting a student health service and, if self-care was undertaken, to determine the source(s) of self-care information. Results indicated that almost two thirds of the subjects had engaged in self-care for the symptoms that led to their visits. The most popular sources of self-care information included family members or friends, prior interaction with a health care provider, and nonprescription medication advertisements. This study did not address the appropriateness of the self-care information obtained; therefore, the quality of the information was not analyzed. Due to the prevalence of self-care among college students, attempts should be made to provide them with objective, high quality, and readily accessible self-care information. This information should be provided as part of an overall effort that encourages students to view health as a personal responsibility. PMID- 2926030 TI - Lyme disease: a case report. PMID- 2926032 TI - Toward a smoke-free campus. PMID- 2926031 TI - An eating disorders hotline: organization, implementation, and initial experience. PMID- 2926033 TI - Mild mitral insufficiency is a marker of impaired left ventricular performance in aortic stenosis. AB - Whether mitral insufficiency is a marker of decreased left ventricular function in patients undergoing aortic valve replacement for sever aortic stenosis was examined. Hemodynamic measurements in 26 patients with pure aortic stenosis (Group 1), 17 patients with aortic stenosis and grade 1 or 2 mitral insufficiency (Group 2) and 19 control patients were compared. All patients were free of significant coronary artery disease. Ventriculograms were digitized for calculation of ejection fraction, ventricular volumes and wall stress. Despite similar aortic valve areas, Group 2 patients had more advanced symptoms. Cardiac index was comparably decreased in Group 1 (2.6 +/- 0.4 liters/min per m2) and Group 2 (2.7 +/- 0.8 liters/min per m2) compared with the control group (3.8 +/- 0.6 liters/min per m2). Left ventricular end-diastolic and end-systolic volume indexes were increased only in Group 2 (119 +/- 35 and 73 +/- 36 ml/m2, respectively). Likewise, end-systolic wall stress was increased only in Group 2 (149 +/- 54 kdynes/cm2). Ejection fraction was decreased to a greater extent in Group 2 (42 +/- 17%) than in Group 1 (59 +/- 13%) as compared with values in the control group (68 +/- 5%). Although an inverse relation existed between ejection fraction and end-systolic stress in all groups, the ejection fraction (extrapolated to end-systolic stress = 0) was decreased in Group 2, and the slope of the relation was increased in Groups 1 and 2. The end-systolic stress/end systolic volume index ratio, an index of ventricular performance, was also decreased to a greater extent in Group 2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2926034 TI - Is mitral regurgitation a useful marker of left ventricular deterioration in aortic stenosis? PMID- 2926035 TI - Significance of hyperventilation-induced ST segment depression in patients with coronary artery disease. AB - To investigate the significance of hyperventilation-induced ST segment depression, 329 consecutive patients with angina and documented coronary artery disease who underwent hyperventilation and exercise tests during pharmacologic washout were studied. The hyperventilation test induced ST segment depression in 79 patients. In 36 of these 79 patients, the electrocardiographic changes occurred early during overbreathing (Group I), whereas in 26 they occurred late during recovery (Group II). Seventeen patients developed ST segment depression both during over-breathing and during recovery (Group III). Group I patients had a higher frequency of history of angina during exercise, multivessel disease and lower tolerance to exercise as compared with patients in Group II. In Group I, the rate-pressure product at the time to onset of ST depression during overbreathing was similar to that during exercise (152 +/- 24 versus 148 +/- 42; p = NS), whereas in Group II the rate-pressure product at the time to onset of ST depression during recovery was comparable with that under control conditions (104 +/- 30 versus 98 +/- 27; p = NS) and far less than that required to produce ischemia during exercise (104 +/- 30 versus 201 +/- 56; p less than 0.0011). In nine Group III patients, the acute administration of propranolol prevented the early hyperventilation-induced ST segment depression, whereas nifedipine abolished the delayed hyperventilation-induced ST segment depression. These findings suggest that early hyperventilation-induced ST segment depression is due to increased oxygen demand in patients with poor coronary reserve and may be prevented by beta-adrenergic blockers, which are useful for lowering oxygen consumption.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2926036 TI - Use of pulmonary capillary wedge pressure to assess severity of mitral stenosis: is true left atrial pressure needed in this condition? AB - There is disagreement concerning the use of the pulmonary capillary wedge pressure (in place of left atrial pressure) in assessing the presence and severity of mitral valve disease. This study was done to assess the accuracy and reliability of an oximetrically confirmed pulmonary capillary wedge pressure in measuring the transvalvular pressure gradient and valve area in patients with mitral stenosis. In 10 patients with mitral stenosis (1 man and 9 women; mean age +/- SD 47 +/- 7 years), pulmonary capillary wedge pressure was measured through an 8F Goodale-Lubin catheter with its wedge position confirmed by oximetry (oxygen saturation greater than or equal to 95%). In addition, a transseptal left atrial pressure was measured through a Brockenbrough catheter and left ventricular pressure was measured through a pigtail catheter. The mean and phasic left atrial and pulmonary capillary wedge pressures were similar (mean left atrial pressure 18 +/- 6 mm Hg; mean pulmonary capillary wedge pressure 18 +/- 8 mm Hg; p = NS). When the pulmonary capillary wedge pressure was used without adjustment for time delay, the transvalvular pressure gradient (9.8 +/- 3.3 mm Hg) and valve area (1.5 +/- 0.5 cm2) were significantly different (p less than 0.05) from the values obtained with use of left atrial pressure (7.2 +/- 2.9 mm Hg and 1.7 +/- 0.6 cm2, respectively). In contrast, when the pulmonary capillary wedge pressure was adjusted for the time delay through the pulmonary vasculature, the difference in gradients averaged only 1.7 mm Hg and the mitral valve areas were similar.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2926037 TI - Feasibility of identifying amyloid and hypertrophic cardiomyopathy with the use of computerized quantitative texture analysis of clinical echocardiographic data. AB - Ultrasound tissue characterization, the evaluation of certain physical properties of a tissue based on its acoustic properties, is an evolving application in echocardiography. The ability to identify acutely and chronically injured tissue has been demonstrated in a number of animal studies, but data in humans are limited. The present study tested the hypothesis that quantitative echocardiographic texture analysis, a method of evaluating the spatial pattern of echoes in echocardiographic images, would differentiate amyloid and hypertrophic cardiomyopathy from normal myocardium. Routine clinical echocardiographic data were obtained on 34 subjects at the Mayo Clinic (10 normal subjects, 10 patients with amyloid heart disease, 8 patients with hypertrophic cardiomyopathy and 6 patients with left ventricular hypertrophy due to hypertension). Standard videotape recordings of these echocardiograms were analyzed at the University of Iowa. Echocardiographic data were digitized with use of a calibrated, 256 gray level digitization system. Quantitative texture analysis was performed on data from the ventricular septum and posterior left ventricular wall in end-diastolic and end-systolic, short-axis and long-axis echocardiographic images. The gray level run length texture variables were able to discriminate hypertrophic cardiomyopathy and amyloid heart disease from normal myocardium and from each other (p less than 0.0083 for comparisons of the quantitative texture features of amyloid versus hypertrophic cardiomyopathy versus normal by multivariate analysis of variance). The texture of the myocardium in hypertensive left ventricular hypertrophy not associated with amyloid or hypertrophic cardiomyopathy was in general not significantly different from that of normal myocardium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2926039 TI - Myocardial contrast echocardiography: a light in the (heart of) darkness. PMID- 2926038 TI - Dipyridamole radionuclide ventriculography: a test with high specificity for severe coronary artery disease. AB - Ventricular dysfunction induced by dipyridamole would be evidence of myocardial ischemia in patients with limited ability to undergo standard exercise testing. Radionuclide ventriculography before and after intravenous dipyridamole infusion was compared with the results of exercise radionuclide ventriculography in a prospective study of 31 patients undergoing coronary angiography. Among these patients, 21 (68%) had significant coronary artery disease (greater than or equal to 50% stenosis), 19 (61%) had severe coronary disease (greater than or equal to 70% stenosis) and 10 (32%) were "normal" (less than 50% stenosis). The left ventricular ejection fraction was calculated, and regional wall motion was scored on a 6 unit scale. In the normal patients, the ejection fraction (+/- SEM) increased 5.6 +/- 2% (units) during exercise and 7.9 +/- 1 units after dipyridamole (both p less than or equal to 0.004 compared with that during rest). However, in patients with coronary artery disease, the ejection fraction failed to increase during exercise or after dipyridamole. In the patients with coronary artery disease, regional wall motion decreased by 4.1 +/- 0.5 units during exercise (p less than 0.003) and by 1.8 units after dipyridamole (p less than 0.02). Receiver operating characteristic analysis demonstrated general comparability between the sensitivity and specificity of exercise and dipyridamole ventriculography, with "optimal" operating points that favored choosing high sensitivity for the former and high specificity for the latter. Specific subsets of patients with severe coronary atherosclerosis were analyzed with use of these criteria. In patients with severe stenosis (greater than or equal to 70%), the sensitivity of dipyridamole ventriculography was 67% compared with 89% for exercise ventriculography. However, at these levels of sensitivity, the specificity of dipyridamole ventriculography was 92% compared with 67% for exercise ventriculography. In this and other subsets of patients, the specificity of dipyridamole ventriculography exceeded that of exercise ventriculography. Thus, it is concluded that dipyridamole radionuclide ventriculography is moderately sensitive and highly specific for detecting severe coronary atherosclerosis. This technique provides a widely applicable, useful alternative to exercise ventriculography in the diagnosis of coronary atherosclerosis in patients who have limited exercise tolerance. PMID- 2926040 TI - Flow characteristics in the dilated left ventricle with thrombus: qualitative and quantitative Doppler analysis. AB - In an attempt to determine whether mural thrombus in a dilated left ventricle is associated with specific flow patterns, a study was undertaken to assess qualitatively and quantitatively the flow characteristics by conventional pulsed and two-dimensional Doppler color flow examination. Forty patients with cardiomyopathy formed the study group (20 with an apical thrombus and 20 without). The groups did not differ with respect to age, gender, origin of ventricular dysfunction, ventricular size and ejection fraction. Guided by the Doppler color flow pattern, a quantitative analysis of flow velocity profile in the ventricular inflow and outflow "compartments" was performed by serial pulsed wave Doppler sampling. Inflow velocity at the ventricular apex was significantly lower in the thrombus group than in the no thrombus group (11.7 +/- 15.3 versus 28.3 +/- 10.5 cm/s, p less than 0.0001). Flow velocities were generally lower in the thrombus group at the other levels in the inflow compartment (that is, mitral anulus, leaflet tips and papillary muscle level). The systolic flow velocity at the apex was similarly significantly lower in the thrombus group than in the no thrombus group (7.1 +/- 8.1 versus 15.3 +/- 7.0 cm/s, p less than 0.001). Additionally, a higher prevalence of mitral regurgitation was noted in the no thrombus group (14 patients) than in the thrombus group (3 patients). Thus, specific abnormal flow profiles are associated with a left ventricular thrombus. Whether the abnormal flow is a primary event in the genesis of left ventricular thrombus or occurs secondary to development of the thrombus cannot be determined from this study. PMID- 2926042 TI - Surface electrocardiography: can arrhythmia circuits be localized? PMID- 2926041 TI - Electrocardiographic localization of the site of origin of ventricular tachycardia in patients with prior myocardial infarction. AB - The utility of the 12 lead electrocardiogram (ECG) in identifying the site of origin of sustained ventricular tachycardia in patients with previous myocardial infarction was studied. A new mapping grid, based on biplanar fluoroscopic imaging of the heart, was utilized for the definition of left ventricular endocardial sites. On the basis of QRS configurations resulting from left ventricular endocardial pacing at disparate sites in 22 patients (Group I), ECG features that were specific for particular sites were identified and used to construct an algorithm. Apical and basal sites were differentiated by the QRS configuration in leads V4 and aVR, anterior and inferior sites by that in leads II, III and V6 and septal and lateral sites were differentiated using leads I, aVL and V1. The algorithm was used to predict the site of earliest endocardial activation during 44 episodes of sustained ventricular tachycardia in a second group of 42 patients (Group II) in a blinded fashion. Anterior sites were correctly predicted in 83% of cases, inferior sites in 84%, septal sites in 90% and lateral sites in 82% of cases. Apical and basal sites were each correctly predicted in 70% of cases, whereas intermediate sites were less well predicted (29 to 55%) on the basis of QRS configuration. Precise localization of the site of origin of ventricular tachycardia (in all three planes) was achieved in 17 cases (39%), and in 16 cases (36%) the site of origin was immediately adjacent to the predicted site. Prediction of the site of origin of ventricular tachycardia from the 12 lead ECG may serve as a useful, time-saving adjunct to, but not a substitute for, activation sequence mapping during ventricular tachycardia. PMID- 2926043 TI - Ventricular fibrillation in six adults without overt heart disease. AB - Findings are described in six patients with no clinical evidence of heart disease who had documented ventricular fibrillation (five patients) or ventricular flutter (one patient). The mean age of the six patients, all men, was 34 years (range 26 to 43). Cardiovascular collapse occurred in all and was followed by successful cardioversion. No patient had electrolyte or QT abnormalities. One patient had slight right ventricular enlargement on M-mode echocardiography, and another had a left ventricular pressure gradient at rest of 30 mm Hg with a normal two-dimensional echocardiogram. Holter electrocardiographic monitoring revealed incessant ventricular tachycardia in one patient and nonsustained ventricular tachycardia in three others. Exercise testing revealed nonsustained ventricular tachycardia in one patient. Ventricular fibrillation was induced at the time of programmed electrical stimulation in four of the six patients. Documented recurrence of ventricular fibrillation or ventricular flutter occurred in three patients, but in only one patient receiving antiarrhythmic drugs. Four patients were treated with amiodarone and one received an automatic implantable cardioverter-defibrillator. All patients are alive after a mean follow-up period of 78 months after the first documentation of their arrhythmia and 37 months after programmed electrical stimulation. Ventricular fibrillation can occur in the apparently structurally normal human heart. Antiarrhythmic treatment can provide effective control of this malignant arrhythmia. PMID- 2926044 TI - Pacemaker-implantation complication rates: an analysis of some contributing factors. AB - An examination of 632 consecutive pacemaker implantations performed at a single institution by 29 implanting physicians over a 5 year period was made to determine which factors affected the 37 perioperative complications experienced. The introducer method of vein access contributed significantly to the complication rate, which was also related to the number of physician implanters on the staff and the makeup of the implantation teams. Of greatest interest was the substantially large incidence of complications experienced by implanters who performed fewer than 12 implantations per year, and particularly the incidence of lead-related complications. PMID- 2926047 TI - Suppression of exercise-induced angina by magnesium sulfate in patients with variant angina. PMID- 2926045 TI - Recognition of abnormal connections of coronary arteries with the use of Doppler color flow mapping. AB - Anomalous connection of a coronary artery to a ventricle or pulmonary artery causes shunting of blood from the coronary circuit and may produce myocardial ischemia. Such a coronary anomaly may occur in isolation or with other defects. Doppler color flow mapping and two-dimensional echocardiography were used to diagnose anomalous coronary connections in 13 patients, 1 day to 7 years of age, over a 1 year period. The diagnoses were anomalous origin of the left coronary artery from the pulmonary trunk in five patients, a coronary artery to left ventricle fistula or coronary artery to pulmonary artery fistula in four patients with other complex defects, right ventricular sinusoids in two patients with pulmonary atresia and intact ventricular septum and an isolated coronary artery fistula in two patients. In all cases, the abnormal coronary connection was recognized on the basis of an abnormal, continuous or to and fro flow pattern in the fistula and its connections as demonstrated by scanning in multiple views with Doppler color flow mapping. The low spatial resolution of Doppler color flow mapping limits the anatomic detail available; nonetheless, it is a significant advance in the noninvasive diagnosis of abnormal coronary connections. PMID- 2926046 TI - Extracellular potassium ion dynamics and ventricular arrhythmias in the canine heart. AB - The relation between extracellular potassium ion activity [( K+]o) and ventricular tachyarrhythmias was studied in an open chest canine model with the use of two protocols. In Protocol I, potassium chloride was administered into the proximal left anterior descending coronary artery at a rate of 0.125 mEq/min for either 20 min or until [K+]o = 20 mEq/liter, whichever came first. In Protocol II, the proximal left anterior descending coronary artery was occluded in one step and was reperfused 20 min later. Fifteen dogs were subjected to Protocol I, nine of which were also subjected to Protocol II. In the latter group, a recovery period of greater than or equal to 1 h separated the two protocols. Local K+ and intramyocardial activities were recorded with use of bifunctional ion-sensitive plunge electrodes at multiple sites located in the region of the left ventricle perfused by the left anterior descending artery and at one site outside of this region. The following variables were recorded and analyzed: Lead II electrocardiogram, heart rate, systemic arterial blood pressure, local [K+]o and its time derivative (dK+/dt), local electrograms and ventricular arrhythmias. Maximal [K+]o and dK+/dt were 23 +/- 3 mEq/liter and 9 +/- 1 mEq/liter per min in Protocol I and 14 +/- 1 mEq/liter and 3 +/- 1 mEq/liter per min in Protocol II, respectively. In both protocols, the occurrence of ventricular arrhythmias correlated with [K+]o (p less than 0.02) as well as with dK+/dt (p less than 0.05). Ventricular arrhythmias were more frequent and more severe in Protocol II than in Protocol I (p less than 0.05). Therefore, whereas K+ dynamics were more pronounced in Protocol I, ventricular arrhythmias were more severe in Protocol II. This occurrence was apparently due, at least in part, to less heterogeneous changes in K+ gradients during constant K+ infusion. It was concluded that, in addition to the magnitude of [K+]o, the rate of change of this variable (that is, dK+/dt) apparently plays an important role in the genesis of ischemic ventricular arrhythmias. PMID- 2926049 TI - Noninvasive evaluation of diastolic function: need for hemodynamically and clinically relevant variables. PMID- 2926048 TI - Differentiation of restrictive cardiomyopathy from pericardial constriction: assessment of diastolic function by radionuclide angiography. AB - Diastolic filling variables were studied in 12 patients with the hemodynamic features of constriction, of whom 5 had restrictive cardiomyopathy, 5 had pericardial constriction and 2 had combined pericardial constriction and restrictive cardiomyopathy. The values were compared with those in 10 normal subjects of comparable age. The filling fractions between 10% and 70% of the diastolic time interval were greater in patients with pericardial constriction than in those with restrictive cardiomyopathy (p less than 0.01 between 20% and 50%, p less than 0.05 at 10%, 60% and 70%), with no overlap. The filling fractions in patients with pericardial constriction were also greater than those in normal subjects between 10% and 60% of the diastolic time interval. The filling fraction was lower in patients with restrictive cardiomyopathy than in normal subjects at 40% of the diastolic time interval (p less than 0.05). The time to peak filling rate in patients with pericardial constriction was shorter (110 +/- 14 ms) than in those with restrictive cardiomyopathy (195 +/- 45 ms, p less than 0.01) or in normal subjects (173 +/- 32 ms, p less than 0.01). The percent of atrial contribution to left ventricular filling was higher in those with restrictive cardiomyopathy (45 +/- 17%) than in those with pericardial constriction (21 +/- 6%, p less than 0.05) or in normal subjects (24 +/- 9%, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2926050 TI - Echocardiographic evaluation of left ventricular diastolic function. PMID- 2926051 TI - Cardiac manifestations of human immunodeficiency virus infection: a two dimensional echocardiographic study. AB - To determine the prevalence of cardiac abnormalities in patients with human immunodeficiency virus (HIV) infection, two-dimensional Doppler echocardiography was performed on 70 consecutive patients with HIV infection, including 51 with acquired immunodeficiency syndrome (AIDS), 13 with AIDS-related complex and 6 with asymptomatic HIV infection. Of the 70 patients, 36% were hospitalized and 64% were ambulatory at the time of evaluation. The average age was 37 years; 93% were homosexual men. Echocardiographic findings included dilated cardiomyopathy in eight patients (11%), pericardial effusions in seven patients (10%) (one with impending tamponade), pleural effusion in four patients (6%) and mediastinal mass in one patient (1%). Among the 25 hospitalized patients, echocardiographic abnormalities were noted in 16 (64%), whereas among the 45 ambulatory patients, the only abnormality noted was mitral valve prolapse in 3 patients (7%) (p less than 0.0001). Dilated cardiomyopathy was the only echocardiographic lesion more common in the 25 hospitalized patients than in 20 hospitalized control patients with acute leukemia. Symptoms of congestive heart failure responded to conventional therapy. Cardiac lesions were associated with active Pneumocystis carinii pneumonia and low T helper lymphocyte counts. Dilated cardiomyopathy of unknown origin may be more common than was previously recognized in hospitalized, acutely ill patients with AIDS, but is uncommon in ambulatory patients with HIV infection. Echocardiography should be considered in the evaluation of dyspnea in hospitalized patients with HIV infection, especially those with dyspnea that is out of proportion to the degree of pulmonary disease. PMID- 2926052 TI - Acquired immune deficiency syndrome: the heart of the matter. PMID- 2926053 TI - Percutaneous aortic balloon valvuloplasty: its role in the management of patients with aortic stenosis requiring major noncardiac surgery. AB - Seven patients with severe aortic stenosis underwent percutaneous aortic balloon valvuloplasty in preparation for major noncardiac surgery. There were four men and three women (mean age 82 +/- 1.3 years, range 78 to 88). A significant reduction in the transaortic pressure gradient from 77 +/- 7.8 to 31 +/- 6.2 mm Hg (p = 0.002) and increase in calculated aortic valve area from 0.5 +/- 0.1 to 1.0 +/- 0.3 cm2 (p = 0.05) was noted. Three of the seven procedures were performed anterograde with use of transseptal puncture: two of the three because of abdominal aortic aneurysm and one because of peripheral vascular disease. All seven patients underwent uncomplicated noncardiac surgery under general anesthesia 10 +/- 4.3 days (range 0 to 29) after aortic valvuloplasty. One patient had exploratory laparotomy, one underwent stabilization of a hip fracture and two underwent resection of an abdominal aortic aneurysm. Of the three other patients who underwent colectomy, one had repeat aortic valvuloplasty and repair of a hip fracture 7 months later and one required exploratory laparotomy without repeat valvuloplasty 7 weeks later. Percutaneous aortic balloon valvuloplasty is an effective and safe procedure that may reduce the risk of general anesthesia and major noncardiac surgery in elderly patients with aortic stenosis. PMID- 2926055 TI - Temporal resolution of mitral regurgitation in patients with mitral valve prolapse: a phonocardiographic and Doppler echocardiographic study. AB - To assess the timing and duration of mitral regurgitation in mitral valve prolapse, 20 patients with a mid-systolic click or late systolic murmur, or both (Group 1) and 16 patients with a pansystolic murmur with late systolic accentuation (Group 2) were studied with phonocardiography and echocardiography including various Doppler techniques. The subjects' ages ranged from 15 to 73 years. Mitral valve prolapse with mitral regurgitation was observed in 15 of 20 patients in Group 1 and in all 16 patients in Group 2. M-mode Doppler color echocardiography demonstrated a mitral regurgitant signal throughout systole and isovolumic relaxation in all but 1 of these 31 patients regardless of the pattern of the systolic murmur. The regurgitant signal was recorded after the click in only one patient with mitral valve prolapse in Group 1. Two of the five patients in Group 1 without two-dimensional echocardiographic findings of mitral valve prolapse had the early systolic signal of mitral regurgitation. The timing and duration of the mitral regurgitant signal detected in patients in Group 1 with pulsed or continuous wave Doppler ultrasound varied with the site of the sample volume or beam direction. In the patients in Group 2, however, the signal was demonstrated throughout systole and isovolumic relaxation by both Doppler methods. Compared with M-mode Doppler color echocardiography, therefore, pulsed and continuous wave Doppler methods were less sensitive and thus inadequate to investigate the timing and duration of mitral regurgitation in mitral valve prolapse, especially in patients with a mid-systolic click or a late systolic murmur, or both, who had mild or eccentric mitral regurgitant jets.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2926054 TI - Effects of pharmacologic coronary hyperemia on echocardiographic left ventricular function in patients with single vessel coronary artery disease. AB - To assess whether pharmacologic coronary vasodilation could provoke new left ventricular wall motion abnormalities in patients with single vessel coronary artery disease, systemic hemodynamics, coronary blood flow velocity and left ventricular wall motion were measured by two-dimensional echocardiography during administration of 10 mg of intracoronary papaverine in 14 patients before and again immediately after left coronary angioplasty (group 1). As a comparison with an intravenous method, left ventricular wall motion was analyzed after 0.56 mg/kg body weight of intravenous dipyridamole in a separate group of 13 patients with single vessel coronary disease (group 2). Heart rate-blood pressure product increased 3% to 6% in papaverine-treated patients and 14 +/- 11% (p = NS) in dipyridamole-treated patients. No angiographic collateral vessels were present in either group. Although intracoronary mean flow velocity measured in the 14 group 1 patients and in 5 normal control subjects during papaverine treatment increased from 125% to 400% of basal flow velocity, papaverine induced new left ventricular wall motion abnormalities in only 5 of the 14 patients before coronary angioplasty. In three of five patients, left ventricular wall motion abnormalities persisted after successful coronary angioplasty. Four of the 14 patients demonstrated augmentation of left ventricular wall motion with papaverine. After intravenous dipyridamole, only 3 of the 13 group 2 patients developed new left ventricular regional asynergy. These data suggest that selective (papaverine) and, most likely, global (dipyridamole) augmentation of coronary flow alone does not reliably identify potential ischemic left ventricular regions affected by critical single vessel coronary artery disease. PMID- 2926056 TI - Left ventricular pressure-length relation during exercise-induced ischemia. AB - The pressure-length relation in normal and ischemic segments was analyzed with use of left ventriculography and simultaneous micromanometry during supine exercise in 9 normal subjects and 12 patients with effort angina. Segmental analysis was done in the right anterior oblique projection using a long axis with three perpendicular, equidistant chords. The apical segment in the 12 patients with coronary artery disease represented the ischemic region. In 5 of the 12 patients with coronary artery disease, the basal segment that showed no exercise induced deterioration in wall motion was used as an intrapatient control (nonischemic segment). In the 12 patients with coronary artery disease, left ventricular ejection fraction decreased (from 65% to 50%, p less than 0.001), end diastolic pressure increased (from 24 to 40 mm Hg, p less than 0.001) and the lowest diastolic filling pressure increased (from 9 to 22 mm Hg, p less than 0.001) during exercise-induced ischemia. In normal subjects, ejection fraction increased (from 64% to 70%, p less than 0.01) with unchanged end-diastolic pressure, whereas the lowest diastolic filling pressure decreased during exercise (from 9 to 3 mm Hg, p less than 0.01). Global left ventricular diastolic pressure volume curves showed an upward and rightward shift during exercise-induced ischemia. Regional pressure-length curves of both nonischemic (n = 5) and ischemic (n = 12) segments were shifted upward in early diastole, but moved to a higher portion of the rest pressure-length curve without an upward shift during mid- to end-diastole. In contrast, the apical segment in normal subjects showed a downward shift during exercise.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2926057 TI - Ischemia-induced diastolic dysfunction: new observations, new questions. PMID- 2926058 TI - Exercise ultrafast computed tomography for the detection of coronary artery disease. AB - Ultrafast computed tomography permits the assessment of global and regional left ventricular function during exercise. To evaluate the feasibility of using this new technique for the diagnosis of coronary artery disease, 27 patients undergoing cardiac catheterization for diagnosis of chest pain were evaluated. Fifteen patients had significant (greater than 50%) coronary artery stenosis by quantitative coronary angiography. One vessel disease was found in 12 patients and multivessel disease in 3. Fourteen (93%) of the 15 patients with significant coronary stenosis had a decrease in ultrafast computed tomographic ejection fraction during exercise from (mean +/- SD) 65 +/- 7% to 60 +/- 7% (p less than 0.001). The tomographic ejection fraction increased greater than 5% units during exercise in 10 (83%) of the 12 patients with normal coronary arteries. The mean tomographic ejection fraction in this group was 68 +/- 6% at rest and 75 +/- 6% at peak exercise (p less than 0.001). Regional wall motion was quantified by analyzing the segmental ejection fraction of 12 30 degree pie segments at each tomographic level of the left ventricle. A new regional wall motion abnormality developed during exercise in 12 (86%) of 14 patients with coronary artery disease; one patient was excluded because of a technical problem in data storage. Eleven (93%) of the 12 patients with normal coronary arteries had normal wall motion during exercise. In no patient with ischemic heart disease were both variables, ejection fraction response and regional wall motion, normal. Exercise ultrafast computed tomography appears to be a useful technique for the evaluation of coronary artery disease in patients with chest pain and predominant single vessel coronary artery disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2926059 TI - Exercise ultrafast computed tomography: preliminary findings on its role in diagnosis and prognosis of coronary artery disease. PMID- 2926060 TI - Percutaneous balloon valvuloplasty in neonates with critical aortic stenosis. AB - Percutaneous balloon valvuloplasty was attempted in 10 newborn infants with critical aortic valve stenosis and severe congestive heart failure. Three had a very small left ventricle and aortic anulus. In one infant, the aortic valve could not be passed, and in another infant, a technical error resulted in severe valvular damage, aortic insufficiency and death. Among the eight patients who had effective dilation, the stenosis was relieved in seven as assessed by a significant decrease in transvalvular pressure gradient, improvement of left ventricular contraction and eventual inversion of the ductal shunting. The procedure failed in the only patient whose dilation was performed with an undersized balloon. Aortic insufficiency occurred in three infants and was severe (perforated cusp) in one, moderate in one whose valve was dilated with an excessively large balloon and mild and transient in one. None of the three infants with a very small left ventricle recovered (two died and one underwent cardiac transplantation). Among the seven infants with a left ventricle of acceptable size, three underwent subsequent aortic valvotomy; one of these died and two bad good results. The remaining four are doing well 16 +/- 5 months later (mean +/- SD) with mild to moderate residual aortic stenosis and normal left ventricular function. In conclusion, percutaneous balloon valvuloplasty is an acceptable alternative to surgery in neonates with critical aortic valve stenosis. Incidence of complications and good relief of the obstruction depend on a careful technique. Immediate results are similar to those of surgery. Late prognosis depends on the quality of the left heart structures. PMID- 2926061 TI - Balloon valvuloplasty for recurrent aortic stenosis after surgical valvotomy in childhood: immediate and follow-up studies. AB - The immediate and intermediate-term effects of balloon valvuloplasty were assessed at cardiac catheterization in nine children with recurrent stenosis after a previous surgical aortic valvotomy. At valvuloplasty the patients ranged in age from 0.35 to 16 years and had undergone surgical valvotomy 0.3 to 12.5 years previously. Balloon valvuloplasty immediately reduced the peak systolic aortic stenosis gradient by 53%, from 88 +/- 9 (mean +/- SEM) to 41 +/- 6 mm Hg (p = 0.004). The left ventricular systolic pressure was reduced from 189 +/- 8 to 157 +/- 8 mm Hg (p = 0.001) and the left ventricular end-diastolic pressure from 17 +/- 1 to 14 +/- 2 mm Hg (p = 0.025). The heart rate and cardiac index remained unchanged. Before valvuloplasty, one patient had 1 + and two patients had 2+ aortic insufficiency. In six of nine patients, balloon valvuloplasty caused no change in the degree of valvular insufficiency. Two patients had a 1 + increase (from 0 to 1 + insufficiency in both), and one patient with no insufficiency developed 2+ aortic insufficiency. Elective follow-up catheterization was performed 0.8 to 2.5 years (mean 1.5 +/- 0.2) after valvuloplasty. At follow-up, the peak aortic stenosis gradient remained significantly reduced from the gradient before valvuloplasty (37 +/- 5 versus 85 +/- 10 mm Hg, p = 0.002). The gradient had not changed significantly from that measured immediately after valvuloplasty (37 +/- 5 versus 38 +/- 5 mm Hg, p = 0.75). At follow-up, aortic insufficiency had decreased from that immediately after valvuloplasty in three patients and had increased in two.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2926062 TI - Elucidation of the natural history of ventricular septal defects by serial Doppler color flow mapping studies. AB - Two-dimensional echocardiography has provided information to aid in the diagnosis and management of infants with ventricular septal defect, but its inability to resolve very small ventricular septal defects and problems with defining ventricular septal defect orifice size (because of overlying muscle or tricuspid tissue) have made it unsuitable as a standard for defining the natural history of ventricular septal defect. In this study, 114 serial two-dimensional Doppler color flow mapping studies were performed to define ventricular septal defect anatomy, location and color flow diameter as an indicator of shunt size in 66 patients (over a 40 month period). Twenty-five patients first studied at 6 months of age (mean age at most recent study 15.9 months) had congestive heart failure and 41 (mean age 45 months) did not. In the congestive heart failure group, there were 24 perimembranous and 1 muscular ventricular septal defect and aneurysm formation was present in 17. Mean (+/- SD) color flow diameter was 8.2 +/- 1.9 mm and color flow diameter/aortic root diameter ratio was 0.63. In the 30 patients who underwent cardiac catheterization, color flow diameter bore a close relation to angiographic diameter (r = 0.96) and pulmonary/systemic flow ratio (Qp/Qs) (r = 0.88). In the patients with congestive heart failure, 4 of the 25 ventricular septal defects, all with aneurysm present or positioned adjacent to the tricuspid valve, became smaller but none closed. Of the 41 patients without congestive heart failure, 21 had a perimembranous defect (15 with aneurysm), 18 had a muscular ventricular septal defect and 2 had a supracristal ventricular septal defect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2926063 TI - Doppler color flow mapping and prediction of ventricular septal defect outcome. PMID- 2926064 TI - Acute effect of disopyramide on atrial fibrillation in the Wolff-Parkinson-White syndrome. AB - Disopyramide was administered intravenously to 54 patients during atrial fibrillation and predominantly pre-excited QRS configuration at the time of electrophysiologic study. All patients had Wolff-Parkinson-White syndrome and no patient had coexistent heart disease. The drug was given during sustained atrial fibrillation (n = 45) or during sinus rhythm before induction of atrial fibrillation for patients whose atrial fibrillation was self-terminating in the control state (n = 9). Atrial fibrillation converted to sinus rhythm within 15 min after disopyramide in 37 (82%) of the 45 patients. The shortest RR intervals between two pre-excited cycles increased from 208 +/- 42 to 293 +/- 117 ms (p less than 0.0001). The average RR interval of all cycles prolonged from 332 +/- 60 to 396 +/- 117 ms(n = 45, p less than 0.0001). The 9 patients in whom pre excitation was abolished after the drug had a significantly longer initial shortest RR interval than that of the 36 patients in whom pre-excitation persisted (246 +/- 47 versus 199 +/- 36 ms, p = 0.0022). No patients developed significant hemodynamic or other adverse effects after disopyramide. These data support the intravenous use of disopyramide in patients with normal ventricular function who have atrial fibrillation and a predominant ventricular response over an accessory atrioventricular pathway. PMID- 2926065 TI - Increased exercise capacity after digoxin administration in patients with heart failure. AB - Failure to objectively assess the effect of digitalis on exercise capacity has resulted in controversy regarding its use in patients with chronic congestive heart failure. To clarify this situation, maximal treadmill testing with respiratory gas exchange analysis was performed on 11 patients (mean age 57 +/- 9 years) with chronic congestive heart failure with and without digoxin therapy. Ten of the 11 had a consistent third sound gallop, and the mean ejection fraction of the group was 24 +/- 10%. Rest heart rate was significantly higher (91 +/- 16 versus 102 +/- 16 beats/min; p less than 0.05) and rest systolic blood pressure was significantly reduced in the absence of digoxin (130 +/- 23 versus 121 +/- 15 mm Hg; p less than 0.05). No differences in heart rate or blood pressure were observed during exercise. Significant increases in ventilatory oxygen uptake were observed with digoxin submaximally (3.0 mph, 0% grade), at the gas exchange anaerobic threshold and at maximal exercise (mean increase of 2.6 ml/kg per min; p less than 0.02). An improvement in the estimated ratio of ventilatory dead space to tidal volume (VD/VT), an index of physiologic efficiency, occurred throughout exercise during digoxin therapy, and there was a significant negative correlation between the change in maximal oxygen uptake and change in maximal estimated VD/VT (r = -0.63; p less than 0.05). Thus, digoxin therapy is associated with a significant improvement in exercise capacity in patients with chronic heart failure, most likely due to an improved matching of ventilation to perfusion. PMID- 2926066 TI - Neutrophil depletion does not prevent myocardial dysfunction after brief coronary occlusion. AB - Recent evidence suggests that oxygen free radicals generated during ischemia or reperfusion may contribute to myocardial dysfunction after brief coronary occlusion ("myocardial stunning"). Because neutrophil leukocytes represent a potential source of oxygen radicals, the concept of whether depletion of neutrophils could attenuate myocardial stunning after 10 min of ischemia was examined. In 16 anesthetized dogs, the left anterior descending coronary artery was perfused by an extracorporeal circuit, either with (n = 8) or without (n = 8) neutrophil filters in the perfusion line. The group with filters had near total absence of neutrophils in blood perfusing the left anterior descending coronary artery territory (16 +/- 8 versus 1,826 +/- 399/microliters in the control group). Systolic myocardial shortening and end-systolic pressure-segment length relations were recorded during rest conditions and during incremental intracoronary infusion of dobutamine (5 to 15 micrograms/min) before and after 10 min of coronary flow occlusion. Before coronary occlusion, systolic myocardial shortening at rest was similar in control (15.4 +/- 1.7%) and neutropenic (12.4 +/- 2.2%) groups. Dobutamine (15 micrograms/min) resulted in increased shortening in both control (18.2 +/- 1.4%, p less than 0.01) and neutropenic (15.8 +/- 1.5%, p less than 0.05) groups and in a leftward shift of the end-systolic pressure length relation. During coronary occlusion, collateral coronary flow to the left anterior descending coronary artery territory was not significantly different in the control (0.10 +/- 0.03 ml/min per g) and neutropenic (0.18 +/- 0.06 ml/min per g) groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2926067 TI - Do neutrophils mediate the phenomenon of stunned myocardium? PMID- 2926068 TI - Nifedipine administered after reperfusion ablates systolic contractile dysfunction of postischemic "stunned" myocardium. AB - Recent evidence suggests that postischemic contractile dysfunction of viable myocardium salvaged by reperfusion ("stunned myocardium") may be a consequence of abnormal calcium flux within the previously ischemic cells. Calcium channel blocking agents have been shown to enhance contractile function of stunned postischemic tissue, but it is not certain whether these improvements in function are due to the profound hemodynamic and vasodilator effects of these agents or to a direct effect on calcium flux within the stunned myocytes. Therefore, the effects of 1) high doses of nifedipine, given intravenously at 30 min after reperfusion, and 2) minute doses of nifedipine, infused directly into the coronary circulation at 30 min after reflow, were assessed and compared in anesthetized open chest dogs subjected to 15 min of transient coronary artery occlusion. As anticipated, intravenous nifedipine significantly reduced arterial pressure and increased regional myocardial blood flow. In addition, intravenous nifedipine restored systolic contractile function of the stunned, previously ischemic tissue to essentially normal preocclusion values: segment shortening averaged 102 +/- 8% versus 26 +/- 11% of baseline at 2 h after treatment in treated versus control dogs, respectively (p less than 0.003). Low dose intracoronary infusion of nifedipine did not alter hemodynamic variables or myocardial blood flow, but did improve segment shortening (90 +/- 9% versus 37 +/ 10% of preocclusion values at 1 h after treatment versus 25 min after reperfusion [that is, pretreatment], respectively; p less than 0.03). These data indicate that the calcium channel blocking agent nifedipine, given 30 min after reperfusion, enhances systolic contractile function of postischemic stunned myocardium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2926069 TI - The increasing importance of a cardiovascular society. PMID- 2926070 TI - Double balloon aortic valvuloplasty in children. PMID- 2926072 TI - Nutrition and behavior. PMID- 2926071 TI - Inferior vena cava plethora with blunted respiratory response. PMID- 2926073 TI - Circadian variation in intestinal protein content in rat fed ad libitum. AB - The circadian variation in protein content in the digestive tract was studied in parallel with food intake in the free-feeding rat maintained under a 12:12 hr light:dark cycle (lights on at 07 hr). Rate of ingestion of a casein-based diet increased progressively during daytime, but most of the intake occurred in the dark. Gastric emptying of proteins lagged by a 3-hr interval behind intake. N content in the intestine divided equally into three segments also increased in the dark. The rise was specific for each segment with the most marked rise in the second segment. Endogenous N levels were high and accounted for at least two thirds of intestinal N levels. There was no net absorption of N in the first intestinal segment due to dilution by endogenous proteins. Absorption was at an average of 70% in the second segment and reached 85% in the distal intestine. The amino acid composition of intestinal protein content reflected endogenous proteins much more than casein. Specific trypsin activity increased distally. The appearance of nitrogenous material (alpha-amino N) in portal blood also followed a circadian variation reflecting the pattern of food intake. In spite of their high level in the intestine, endogenous proteins did not lead to an appreciable appearance of nitrogenous material in the blood except at 10 hours. Results indicate that fluctuation in food intake is accompanied by complex variations in protein contents of the digestive tract. Endogenous protein levels were high and seemed to have a slow turnover. PMID- 2926074 TI - Modifications of the electrical activity in the ventromedial hypothalamic nucleus and the lateral hypothalamic area of 24-hour food-deprived rats. AB - The amplitude of the electrical activity of the ventromedial hypothalamic nucleus (VMH) and lateral hypothalamic area (LH) was evaluated in rats after 24-hr food deprivation to determine the effects of the diet they had received before fasting. Bioelectrical potentials were registered by means of monopolar electrodes. In rats after 24-hr food deprivation an increase in the absolute values of the amplitude of the electrical activity of the VMH and LH was found; this effect was more pronounced in the LH. Comparing the amplitude of the electrical activity of the VMH and LH, we found it to be always higher in the VMH in ad libitum fed rats, while in 24-hr food-deprived rats the electrical activity was always higher in the LH. The extent of changes depended on the diet the rats had received before fasting--they were most marked in rats fed on a high-protein diet and less marked in rats fed on either a standard or a high-fat diet before food deprivation. PMID- 2926075 TI - Negative contrast in the consumption of sucrose and quinine adulterated sucrose solutions. AB - Rats shifted from a 40% sucrose solution to a quinine-adulterated (30 mg/100 ml) 40% sucrose solution showed a reduction in consumption to a level considerably below that of animals exposed to only the quinine-adulterated solution. The animals tended to recover from this negative contrast effect over a 5-day postshift period and, in general, the degree of contrast was about equivalent to that of animals shifted from a 32% to a 4% sucrose solution. There were no sex differences in the rats shifted from 32% to 4% sucrose, but female rats shifted to the quinine-adulterated sucrose showed larger contrast effects than male rats exposed to the same shift. PMID- 2926076 TI - Effect of growth hormone on the glomerular filtration response to a protein meal. AB - The role of dietary protein intake in the pathogenesis of progressive renal disease has been recently reexamined. Studies of both animal and humans with chronic renal disease have shown that restriction of dietary protein may slow the progression of the decline in renal function. This occurs because of a decrease in intraglomerular blood flow and pressure. The mechanism of this phenomenon is not known. The effect of protein intake on renal function is thought to be hormonally mediated. Since growth hormone can increase renal blood flow as well as GFR, we tested the hypothesis that the presence of growth hormone is necessary for the increase in glomerular filtration rate (GFR) seen after the ingestion of a protein meal. We evaluated the change in GFR after a standardized mixed protein meal in 13 patients with growth hormone deficiency. Neither basal creatinine clearance after an overnight fast (76 +/- 17 ml/min/m2; mean +/- SD) nor maximum increment after a 50 g/m2 protein meal (33 +/- 11 ml/min/m2) differed in these growth hormone-deficient patients from 16 normals controls (76 +/- 18 and 30 +/- 15 ml/min/m2, respectively). Twelve hours after an injection of exogenous growth hormone, 0.06 mg/kg up to a maximum of 5 mg, the GFR response to a protein meal did not differ from the pretreatment response (77 +/- 19 and 32 +/- 17 ml/min/m2, respectively). We conclude that the presence of physiologic amounts of growth hormone is not necessary for the GFR response to a standard protein meal. PMID- 2926077 TI - Calcium bioavailability and iron-calcium interaction in orange juice. AB - We have determined the effects of orange juice on calcium bioavailability from CCM (a combination of CaCO3, citric acid, malic acid, 5:1:1, mol/mol/mol) and iron-calcium interaction by using whole body isotope retention techniques in rats. The mean calcium retention values from CCM were 42.8% from orange juice and 33.0% from water, a control. Orange juice significantly (p less than 0.05) improved calcium bioavailability. This enhancement of calcium absorption is independent of orange juice's pH and citric acid. Iron absorption from orange juice with CCM (36.7%) was also significantly higher than that from control (water) plus CCM (12.3%). Ascorbic acid at levels naturally present in orange juice failed to improve iron retention (12.3% vs 12.5%) from water plus CCM. In contrast, citric acid (at orange juice level) significantly (p less than 0.05) promoted iron absorption in the presence of CCM (8.0% vs 23.7%). The benefit of citric acid on iron-calcium interaction is enhanced by ascorbic acid. In the presence of both citric acid and ascorbic acid, at orange juice levels, iron absorption from water plus CCM (37.6%) was comparable to that from water without CCM (34.5%). These results show orange juice can deliver bioavailable calcium from CCM with minimal inhibition of iron absorption. Citric acid and ascorbic acid are likely the major orange juice components that contribute to the alleviation of iron absorption inhibition by CCM. PMID- 2926078 TI - Absorption of cobalamin (vitamin B12) administered via jejunostomy. AB - Absorption of cobalamin (Cbl) administered via feeding jejunostomy (J) was compared with that given by mouth (PO) to study the role of transgastric passage in its binding to gastric Intrinsic Factor and subsequent ileal absorption. Modified Schilling tests were performed on 10 patients, each patient serving as his own control. A labeled Cbl capsule was dissolved in 10 cc of water, 7 cc (containing approximately 0.4 microCi 57Co) measured in a syringe and administered PO or via J, followed by 30 cc of water. The remaining solution was used for counting. Starting 1 hour later, following 1 mg of IM cyano-Cbl USP to saturate body storage sites of Cbl, urine was accurately collected for 24 hours and a 4-ml aliquot analyzed for 57Co. Results are expressed as % of tracer excreted in the urine (normal: greater than 7%). The test was repeated in 1 week through the alternate route using the identical protocol. In the eight patients in whom results could be analyzed, absorption was 21.18 +/- 5.83% in J group (range: 5.8-51.9%) and 9.75 +/- 2.62% in PO group (range: 1.9-24.2%). This difference was highly significant p = 0.02) using the paired Student's t-test. Route of the first test (PO or J) made no difference. It is concluded that cobalamin (vitamin B12) administered via jejunostomy is absorbed to a degree significantly greater than that given by mouth. PMID- 2926079 TI - Thiamin deficiency in clinical practice: a controversy. PMID- 2926080 TI - Clinical significance and allergenic cross-reactivity of Euroglyphus maynei and other nonpyroglyphid and pyroglyphid mites. AB - The clinical significance and allergenic cross-reactivity of the storage mites Lepidoglyphus destructor and Acarus siro and the house dust mites Dermatophagoides pteronyssinus and Euroglyphus maynei were investigated with specific IgE antibodies by use of the RAST and the RAST-inhibition technique. RAST-positive sera were obtained from 64 Swedish farmers whose test results were positive to at least one of the four mite species. E. maynei was shown to be a common cause of sensitization among the whole farming population with a prevalence of 4.5% of positive RAST reactions. Farmers with asthma alone or in combination with rhinitis were more often sensitized to storage mites and house dust mites than farmers with rhinitis only. No significant correlation was found between positive RAST resuts to L. destructor and E. maynei on the one hand and L. destructor and D. pteronyssinus on the other. Statistical significance was reached only between RAST results to E. maynei and D. pteryonssinus. However, by RAST-inhibition studies E. maynei was shown to possess its own unique allergen(s). PMID- 2926081 TI - Analysis of the wheal-and-flare reactions that follow the intradermal injection of histamine and morphine in adults with recurrent, unexplained anaphylaxis and systemic mastocytosis. AB - It has been suggested that patients with recurrent, unexplained anaphylaxis may be more responsive, and patients with systemic mastocytosis, less responsive, to mast cell-derived mediators, including histamine, compared to normal subjects. This would help explain why patients with recurrent, unexplained anaphylaxis have an anaphylactic response and, conversely, why patients with systemic mastocytosis can tolerate high levels of plasma histamine. To test this hypothesis, intradermal titrations (0.02 ml of solution from 1 ng/ml to 2 micrograms/ml) of histamine and morphine sulfate (MS) (10 ng/ml to 10 micrograms/ml) were administered to normal volunteers (N = 15), patients with recurrent, unexplained anaphylaxis (N = 10), and patients with systemic mastocytosis (N = 18). Antihistamines were stopped at least 72 hours before the study. Resultant areas of wheal and flare were determined with a computerized morphometric system. Comparison of any two given means at each dose of histamine or morphine with the two-sample Student's t test with Bonferroni inequality demonstrated no significant differences (p greater than 0.05) among the three groups. The median amount of MS or histamine required to produce a half-maximal response was compared for equality. None of the differences observed reached statistical significance, in agreement with the similarity of the dose-response curves. An analysis of the correlation between response to MS and to histamine in individual subjects revealed the responses to be significantly correlated in all cases, with the exception of wheal in patients with recurrent, unexplained anaphylaxis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2926082 TI - Analysis of the stabilizing effect of epsilon-aminocaproic acid by electrophoretic techniques and immunoblotting. AB - The effect of epsilon-aminocaproic acid (EACA) on the degradation of aqueous pollen extracts was studied by isoelectric focusing, sodium dodecyl sulfate polyacrylamide gel electrophoresis, and immunoblotting. The extracts were stored at 4 degrees C for 7 days and at 37 degrees C for 1, 4, and 7 days. Addition of 0.1 mol/L of EACA before storage partly protected the extract from degradation. The protective effect of EACA could be demonstrated most clearly by immunoblotting, suggesting that more epitopes were preserved in an antigenic configuration. The stabilizing effect increased with higher EACA concentrations. PMID- 2926083 TI - The toxicity of constituents of cedar and pine woods to pulmonary epithelium. AB - Occupational exposure to cedar and pine woods and pine resin (colophony) can cause asthma and chronic lung disease. Prior studies suggest that plicatic and abietic acids are responsible for the asthmatic reactions that occur in cedar wood and colophony workers; however, the etiologic mechanism(s) of the chronic lung disease is unknown. To determine if plicatic acid from cedar wood and abietic acid from pine resin could directly damage lung cells, we exposed monolayers of rat type II and human A549 alveolar epithelial cells, intact rat lungs, and rat tracheal explants to solutions of plicatic and abietic acids. As indices of injury, we measured lysis of alveolar epithelial cells with a 51Cr technique, quantitative desquamation of epithelial cells from tracheal explants, and histologic alterations in tracheal explants and intact lungs. Plicatic and abietic acids both caused dose- and time-dependent lysis of alveolar epithelial cells. Instillation of plicatic and abietic acids into rat lungs produced bronchial epithelial sloughing. Abietic acid also caused destruction of the alveolar epithelium. The addition of either acid to rat tracheal explants caused epithelial desquamation that was dose- and time-dependent. Our results suggest that plicatic acid, a unique constituent of cedar wood, and abietic acid, the major constituent in pine resin, can produce lytic damage to alveolar, tracheal, and bronchial epithelial cells. We hypothesize that repeated occupational exposure to these substances might promote the chronic lung damage observed in some cedar- and pine-wood workers and in electronic workers exposed to colophony. PMID- 2926084 TI - Expression of complement receptors type 1 (CR1) and type 3 (CR3) on circulating granulocytes in experimentally provoked asthma. AB - Neutrophils demonstrate increased complement receptor activity, measured by rosetting of C3b-coated erythrocytes, after asthma that was provoked experimentally. However, it is not clear whether the increased rosetting is due simply to increase in receptor numbers or whether other factors, such as cell adhesiveness, are involved. We have therefore enumerated granulocyte complement receptors, after asthma provoked experimentally, with monoclonal antibodies against the receptors and flow cytometry. There was a maximal 28.2 +/- 7.5% and 33.4 +/- 9.5% (mean +/- SEM; n = 15) increase in granulocyte CR1 and CR3, respectively, at 3 hours after asthma induced by antigen. There was a maximal 32.0 +/- 7.3% (mean +/- SEM; n = 7) increase in granulocyte CR1, but no change in granulocyte CR3, at 1 hour after exercise-induced asthma. No significant changes in granulocyte CR1 or CR3 were observed up to 6 hours after methacholine challenge, or after exercise in subjects who did not develop exercise-induced asthma. There was a maximal 33 +/- 9% (mean +/- SEM; n = 8) increase in granulocyte CR1 at 30 minutes, but no increase in granulocyte CR3, after histamine challenge of subjects with asthma. Incubation of whole blood with histamine in vitro did not lead to any enhancement in expression of granulocyte CR1. This suggests that antigen- and exercise-induced release of histamine may augment granulocyte CR1 expression through an indirect mechanism. These data indicate that there is increase in the numerical expression of CR1 on granulocytes, after asthma provoked experimentally, which is accompanied by increases in granulocyte CR3 after bronchoprovocation with antigen, but not histamine or exercise. PMID- 2926085 TI - Dissociation of cutaneous vascular permeability and the development of cutaneous late-phase allergic reactions. AB - Cutaneous late-phase allergic reactions (LPR) are characterized by an early, immediate hypersensitivity whealing reaction followed by persistent, localized induration that peaks 6 to 8 hours later. In this study we used rodents to examine the relationship between vascular permeability (VP) and induration during LPR. Efflux of macromolecular tracers from the vasculature into skin was measured with the use of radiolabeled albumin and neutral dextran tracers having large molecular radii. To induce LPR immunologically, we used either intradermal injections of antirat IgE or passive cutaneous sensitization with IgE antidinitrophenyl followed 24 hours later by intravenous injection of albumin dinitrophenyl. [125I]albumin and [3H]dextran tracers were injected intravenously before and at various intervals after the induction of LPR. Although a marked increase in VP occurred within the first 30 minutes after induction of mast cell degranulation, analysis of radiolabeled tracer accumulation at 2, 4, 8, and 24 hours failed to demonstrate any further increase in VP. These findings indicate that the induration observed in rodent LPR is not associated with increased VP beyond the immediate hypersensitivity stage and suggest that impairment of lymphatic drainage, cellular infiltration, and/or fibrin deposition are contributing factors. PMID- 2926086 TI - Long-term prophylaxis with C1-inhibitor (C1 INH) concentrate in patients with recurrent angioedema caused by hereditary and acquired C1-inhibitor deficiency. AB - A case of hereditary angioedema (HAE) type I (inherited C1-inhibitor [C1 INH] deficiency) and a case of late-onset acquired C1 INH with angioedema is described. In both patients, long-term prophylaxis with C1 INH had become necessary because treatment with danazol and epsilon-aminocaproic acid was not effective or not tolerated. Consequently, both patients received a pasteurized concentrate of C1 INH continuously for a period of 1 year in a dosage that kept them free of symptoms. The patient with HAE was administered 500 units of C1 INH intravenously every 4 or 5 days, whereas the patient with acquired angioedema required 1000 units of C1 INH every 5 days. As a result of this long-term prophylaxis, both patients became free or nearly free from their episodes of cutaneous and internal edema. The low plasma levels of C1 INH, C4, and C2, rose. In the patient with acquired C1 INH deficiency, the swellings increasingly reappeared after 10 months, although the patient's antibody titer did not rise during treatment. No side effects were recorded during therapy. In particular, both patients remained HIV and hepatitis B antibody negative. PMID- 2926087 TI - Comparison of results of skin prick tests (with fresh foods and commercial food extracts) and RAST in 100 patients with oral allergy syndrome. AB - One hundred adult patients with a history of oral allergy syndrome (OAS) after ingestion of fruits and vegetables, 77 patients with hay fever and 13 with skin prick tests and RAST positive to pollens but without seasonal symptoms, and 32 normal nonallergic control subjects, had Phadebas RAST and skin prick tests with commercial extracts (CSPT) and with fresh foods (FFSPT) to assess the reliability of these three tests. Sensitivity was better with FFSPT for carrot, celery, cherry, apple, tomato, orange, and peach; better with CSPT for peanut, pea, and walnut; and better with RAST for hazelnut. Specificity, negative predictive value, and positive predictive value of the three tests were determined for apple, carrot, hazelnut, orange, pea, peanut, and tomato. Specificity in the patient groups ranged between 40% (pea) and 100% (apple) for CSPT, between 61% (peanut) and 87% (carrot) for RAST, and between 42% (carrot) and 93% (peanut) for FFSPT. However, all tests were negative in the control group. Thus, false positive results may result from cross-reactivity with pollen allergens. The diagnostic accuracy of these tests in the population with OAS proved comparable for peanut, carrot, hazelnut, and pea. FFSPT proved more sensitive than CSPT or RAST in confirming a history of OAS to certain alimentary allergens, such as apple, orange, tomato, carrot, cherry, celery, and peach. PMID- 2926088 TI - AIDS in women and children. PMID- 2926089 TI - Short-term medical service in the developing world. AB - Medicine as it is practiced in the developing world is far removed from medicine as we know it in the United States. It is the authors' opinion that the developing world offers a stimulating environment medically, culturally, and ethically. Those physicians who devote some portion of their careers to practicing in the developing world reap significant rewards. The authors describe how they found and selected medical situations in the developing world and the experiences they had delivering health care in those situations. PMID- 2926090 TI - Women surgeons: a national survey. AB - In order to add to the data on women surgeons as well as to clarify concerns raised in the literature, a questionnaire survey of fully trained women surgeons was conducted between 1983 and 1986. The 386 responses were analyzed and the results are presented here. Findings show that women surgeons are young (median age 37), board certified (77%), and practicing in varied settings. They work a median of 60 hours per week, are progressing academically (54% assistant, 20% associate, and 7% full professors), and are involved in professional organizations (98%). They feel that their family responsibilities have enhanced their lives and benefited their careers. The majority (88%) would choose to be surgeons again. Worrisome findings warranting further investigation are the disparity in earnings between male and female surgeons and the gender related problems still experienced by significant numbers of women during the application and residency process. Additional studies are needed to define and clarify the career patterns of women surgeons. PMID- 2926091 TI - Child care--a women's health issue. PMID- 2926092 TI - Advocating children's health needs. PMID- 2926093 TI - Synergistic inhibition of DNA synthesis in Ehrlich ascites tumour cells by a combination of unsaturated fatty acids and hyperthermia. AB - Wide attention has been given to hyperthermia as a new measure for cancer treatment. Clinical trials of hyperthermia, as they possess antitumour activity on some occasions. When cells were incubated with oleic we examine if fatty acids exert a synergistic effect on Ehrlich ascites tumour cells when combined with hyperthermia, as they possess antitumour activity on some occasions. When cells were incubated with oleic acid and linoleic acid (unsaturated fatty acids) at 37 degrees C, the DNA synthesis of cells was significantly inhibited. Palmitic and stearic acids, which are saturated fatty acids, did not suppress DNA synthesis. Hyperthermic treatment without the presence of fatty acids at 42 degrees C for 1 h decreased DNA synthesis to 62% of the control level of 37 degrees C. The combination of an unsaturated fatty acid and hyperthermia synergistically suppressed DNA synthesis. When the cells were incubated in serum-free medium containing 0.1% albumin, unsaturated fatty acids were more effective in inhibiting DNA synthesis. However, saturated fatty acids had little or no effect on DNA synthesis in control or hyperthermia-treated cells. These results indicate that unsaturated fatty acids are useful for enhancing the inhibitory effect of hyperthermia on DNA synthesis, which may increase the in vitro antitumour effects of hyperthermia. PMID- 2926094 TI - Differing hepatotoxicity and lethality after subacute trichloroethylene exposure in aqueous or corn oil gavage vehicles in B6C3F1 mice. AB - Subacute toxicity of trichloroethylene (TCE) was evaluated in male and female B6C3F1 mice using corn oil or aqueous gavage vehicles. Mice received oral doses of TCE five times a week for 4 weeks at 600, 1200 and 2400 mg/kg/day for males and 450, 900 and 1800 mg/kg/day for females. Vehicle control mice were dosed with either corn oil or a 20% aqueous solution of Emulphor. A dose-related increase in lethality occurred in male and female mice receiving TCE in Emulphor but not corn oil during the first week of treatment. Lethality was consistent with central nervous system depressant effects of TCE. After 4 weeks of exposure, body weights were not altered by TCE but liver/body weight ratios were uniformly increased by TCE administered in either vehicle in both sexes. Only male mice treated with TCE in corn oil, however, sustained elevations in serum enzyme levels, accompanied by liver histopathology. TCE in corn oil produced inflammation-associated focal necrosis in 30-40% of the male mice, with increasing severity from low to high dose. Lipid accumulation, as indicated by Oil-Red O staining, was most prevalent in male mice treated with TCE in corn oil but also occurred to a lesser degree in animals receiving either gavage vehicle alone. This study indicates that the type of oral gavage vehicle is an important factor in determining the nature of TCE toxicity. PMID- 2926095 TI - Nasal tumours in rats after severe injury to the nasal mucosa and prolonged exposure to 10 ppm formaldehyde. AB - To study the significance of damage to the nasal mucosa for the induction of nasal tumours by formaldehyde in rats, a long-term inhalation study was conducted in which male rats with severely damaged or undamaged nose were exposed 6 h/day for 5 days/week to 0, 0.1, 1.0 or 10 ppm formaldehyde vapour for 28 months, or for 3 months followed by a 25-month observation period. The damage to the nasal mucosa was induced by bilateral intranasal electrocoagulation. The total number of rats used was 720, 480 with damaged and 240 with intact nose. Compound-related degenerative, inflammatory and hyperplastic changes of the nasal respiratory and olfactory mucosa were invariably observed when rats with intact nose were exposed to 10 ppm but not when exposed to 1.0 or 0.1 ppm formaldehyde. Nasal electrocoagulation increased the incidences of formaldehyde-induced rhinitis, hyper- and metaplasia of the respiratory epithelium, and degeneration and hyper- and metaplasia of the olfactory epithelium. In addition, exposure to 10 ppm formaldehyde for 28 months produced nasal squamous cell carcinomas in rats with damaged nose (15/58) but not in rats with intact nose. Three months of exposure to 10 ppm formaldehyde or exposure to 0.1 or 1.0 ppm formaldehyde for 28 months had no such effect. It was concluded that severe damage to the nasal mucosa may contribute to the induction of nasal tumours by formaldehyde. PMID- 2926096 TI - Effects of subchronic parathion administration on sodium salicylate excretion kinetics in female rats. AB - Organophosphorus (OP) pesticides are considered to be environmental contaminants, and chronic exposure to low levels through the diet may affect drug action. To study this possible interaction, ethyl parathion was administered by intubation to female rats for 35 consecutive days at a dose of 0.05 or 0.2 mg/kg of body weight per day. At 7, 21 and 35 days after parathion was initiated, rats were administered a single dose of 20 mg/kg sodium salicylate intraperitoneally. Total salicylates, salicylic acid (SA), salicyluric acid (SU) and gentisic acid (GA) were determined in urine. At 7 days, parathion treatment slowed the excretion of total salicylates. This effect was more evident at longer treatment times. Total excretion of SA was increased at the expense of GA at 7 days. However, this effect was reversed at 21 and 35 days. Excretion of SU was drastically diminished after 21 days of treatment with parathion. The results suggest that subchronic oral administration of parathion to female rats changes the excretion kinetics of sodium salicylate through combined effects on renal excretion mechanisms and biotransformation processes. Thus, exposure to low concentrations of environmental contaminants may produce important changes in drug action. PMID- 2926097 TI - Disposition of methacrylonitrile in rats and distribution in blood components. AB - The interaction of 2[14C]methyl-2,3[14C]acrylonitrile (MeAN) with the components of blood and its disposition in male Sprague-Dawley rats has been investigated. Following an oral administration of 100 mg/kg (0.5 LD50, 8 microCi/kg), the rats excreted 43% of the [14C] in the urine, 15% in the feces and 2.5% in the expired air as 14CO2 in 5 days. Hydrogen cyanide (H14CN) was not detectable. The red blood cells retained significant amounts of radioactivity for more than five days after administration, whereas the [14C]-activity in plasma declined sharply. More than 50% of the radioactivity in erythrocytes was detected as covalently bound to cytoplasmic (hemoglobin) and membrane proteins. A small amount of radioactivity was also found in the heme fraction. About 13% of the total dose administered was recovered as thiocyanate in the plasma and the urine. These results suggest that the toxicity of MeAN may be attributable to the whole molecule and not entirely to the in vivo liberation of cyanide. PMID- 2926098 TI - An evaluation of the acute toxic properties of liquids derived from oil sands. AB - The acute toxicity of three materials derived from Athabasca Oil Sands--(1) bitumen plus naphtha, (2) untreated naphtha (0-250 degrees C) and (3) synthetic crude oil (0-500 degrees C)--was assessed in a battery of tests. In acute oral studies, all three test materials exhibited a low order of toxicity (LD50 greater than 5.0 g kg-1). The acute dermal LD50 was also low (greater than 3 g kg-1) for each test material. All three materials were judged to be 'slight' ocular irritants. Acute inhalation studies (6-h exposures at the maximum attainable concentrations) produced varied responses. Bitumen plus naphtha administered at a concentration of 1.46 mg l-1 did not cause mortality in exposed rats or mice. Lung discoloration was the only necropsy finding of note. Untreated naphtha administered at a concentration of 10.6 mg l-1 was lethal to essentially all of the mice; but only two rats died. Necropsy findings included elevated weights in the liver and kidneys of the exposed mice, elevated lung weights in male rats and elevated liver weights in female rats. Synthetic crude oil administered at a concentration of (4 mg l-1) was lethal to 5/10 mice, but none of the rats (0/10) died. Severe hair loss was noted in the surviving mice, and slight alopecia was also observed in rats. Both species exhibited elevated liver weight, and elevated lung weight was noted in female rats. PMID- 2926099 TI - Age, cohort, and time-period confounds in aging research. AB - 1. Cross-sectional studies of age-related changes or developmental patterns contain the inherent confound of age and cohort. 2. Longitudinal studies of age related changes or developmental patterns contain the inherent confound of age and time-period. 3. Many complex research designs and decision rules have been developed in an attempt to disentangle these confounds. These designs and decision rules are only useful if their assumptions are met. 4. It is important to logically determine when the age, cohort, and time-period confounds discussed in this article are important to resolve in a nursing study and when the confounds do not directly relate to the clinical or theoretical merit of a study. PMID- 2926100 TI - Feeding the frail elderly. AB - 1. Frail older adults need to be fed carefully and observed closely while eating to prevent choking and aspiration of food and fluids. They choke more easily on clear liquids than on soft foods with some texture. 2. The licensed nurse is responsible for evaluating the physical status of frail older adults before feeding them and for assuring that less qualified personnel are aware of the dangers and specific precautions in feeding these types of patients. 3. The use of nutritious finger foods allows frail older people some degree of independence by encouraging them to feed themselves whenever possible. Careful menu planning can result in a variety of nutritious foods for older people. 4. Soft-cooked vegetables and fruits are more appetizing and acceptable to frail edentulous older adults than pureed or ground foods. Making mealtime special may be one of their few pleasures. 5. Frail older adults should remain in a sitting or semi Fowler's position for at least one to two hours after eating to prevent possible regurgitation and aspiration of food or fluids. PMID- 2926102 TI - Adult day care: how families of the dementia patient respond. AB - 1. The experience of caring for a family member with dementia in the home is a physical, emotional, and financial strain for the majority of caregivers. 2. The availability of community as well as family supports are variables which will influence how well a caregiver will cope. 3. Though the use of adult day care did not significantly decrease the reported stress for caregivers as a group, some did experience less strain. 4. Caregiver response to adult day care is variable and complex. Gerontological nurses who counsel caregivers should help them be realistic about their expectations for adult day care. PMID- 2926101 TI - Prevent elder abuse--using a family systems approach. AB - 1. Family stressors occur when the adult child is caregiver for an elderly parent, particularly when care is intensive or protracted. Under certain circumstances of high risk, severe and unresolved strains in intergenerational relationships can develop into elder abuse. 2. Elder abuse is a non-accidental act or omission that causes physical, psychological, or financial harm to an older person. 3. Using a family systems perspective, an original validated instrument is presented that evaluates the risk of elder abuse in the home (REAH). Using this instrument, the nurse can construct two profiles of 1) the older person, including personal data and dependency needs, and 2) the caregiver, including personal data and family dynamics. 4. The instrument provides a simple method for recognizing family strains and noting changes over time within the family system. Appropriate interventions and referrals can be initiated that may avert the crisis of elder abuse. PMID- 2926103 TI - The importance of hope in the care of the elderly. PMID- 2926104 TI - Pooling resources to benefit elderly clients. PMID- 2926105 TI - Epidemic bloodstream infections from hemodynamic pressure monitoring: signs of the times. PMID- 2926107 TI - Occupational exposure to influenza--introduction of an index case to a hospital. AB - The epidemiology of influenza in the hospital is frequently confounded by failure to separate community-acquired from nosocomial transmission. An 83-year-old woman was hospitalized one day after returning from Asia with complications resulting from acute influenza A (H3N2) infection; she was the first culture-confirmed case in the region during the 1987-1988 influenza season, and her illness antedated other influenza cases in the area by at least four weeks. The patient shed virus at least four days after admission and transmitted influenza to her primary physician; both had received trivalent influenza vaccine four weeks earlier. Surveillance data from the 28 health care providers (HCPs) in contact with the index case (mean age: 34.5 years; median time of contact: four hours, none receiving vaccine) revealed no evidence of transmission as detected by paired type-specific complement-fixation antibodies and throat culture (20 subjects) or acute serologies and culture (7 subjects). No febrile respiratory illnesses were detected among other patients on the same ward, although three were reported among HCPs. Thus, neither secondary spread of influenza from infected patient to hospital HCPs nor nosocomial transmission apparently took place, although transmission did occur to the primary physician. PMID- 2926106 TI - Epidemic bloodstream infections associated with pressure transducers: a persistent problem. AB - Twenty-four outbreaks of nosocomial bloodstream infection (BSI) were investigated by the Centers for Disease Control from Jan 1, 1977 to Dec 31, 1987. Intravascular pressure monitoring devices (transducers) were the most commonly identified source of bacterial and fungal BSI outbreaks and were implicated as the source of infection in eight (33%) outbreaks. These included outbreaks caused by Candida parapsilosis (2), Serratia marcescens (2), Klebsiella oxytoca (1), Pseudomonas cepacia (1), Acinetobacter calcoaceticus (1), and one polymicrobial bacteremia outbreak due to Acinetobacter, Pseudomonas, Citrobacter, and Enterobacter species. In all eight outbreaks, reusable transducers improperly disinfected or fitted with domes that had been improperly sterilized served as reservoirs for the organism. Compared with nosocomial BSI outbreaks not related to transducers, those in which transducers were implicated as a reservoir involved a larger mean number of patients (24 v 9; P = 0.007), and were significantly more likely to involve intensive care unit patients (23/24 v 3/9; P = 0.025) and to have a longer mean duration (11 v 3 months; P = 0.007). These findings show that the characteristics of transducer- and non-transducer-related BSI outbreaks differ, and that centers using intravascular pressure monitoring devices must be aware of and implement recommended infection control strategies for care and maintenance of these devices. PMID- 2926108 TI - A no-rinse alcohol antiseptic and a no-touch dispenser for hand decontamination. PMID- 2926109 TI - Clinical grading--de-grading or an opportunity? PMID- 2926110 TI - Families in ICU: their needs and anxiety level. AB - In the course of their care-giving activities nurses deal with family members as well as with patients. The dimension of family involvement becomes even more crucial when patients are hospitalised in the Intensive Care Unit (ICU). The purpose of this study was to identify: 1. The perceived needs and anxiety levels of adult family members of ICU patients; 2. The relationship between perceived needs and situational anxiety levels; and 3. The sociodemographic factors having an influence on the needs and anxiety level of family members. Over a 10-week period, a convenience sample of 207 subjects was formed from the total adult population of immediate family members visiting a patient in a 9-bed ICU of a 388 bed university hospital. The data were gathered by a face to face interview, a self-report questionnaire of the French version of the Critical Care Family Needs Inventory (Molter & Leske, 1983), and the A-Scale of the State Trait Anxiety Inventory (Spielberger, 1970). The major variables investigated were: family needs; situational anxiety; on-site sources of worry; level of knowledge with respect to the ICU setting from experience or pre-surgery education; and finally, sociodemographic data. The sample was predominantly female (75%) and the mean age was 45.43 s.d.-15.19, ranging from 18 to 91 years. The average number of respondents per family was 2.3 with a range of 1 to 5. The Situational Anxiety Scale of the STAI yielded a mean score of 47.88 +/- 12.02 ranging from 21 to 76.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2926111 TI - Road to recovery. AB - The role of the nurse in giving information to patients has grown considerably following the work of researchers such as Hayward (1975), Boore (1978) and Wilson Barnett (1978). From admission to discharge the nurse has a valuable educational role to play in helping patients come to terms with their present position and preparing them for the future. The questions facing nursing now are not whether nurses should undertake this role, but how well do they provide information? Do patients act on advice? And how far should relatives be included in the process of patient education? These are the questions that prompted the present study, in which 43 people completed questionnaires 6 to 8 weeks following discharge from hospital after cardiac surgery. Eighty-two per cent were completely or 'on the whole' satisfied with the information given, though the perceived adequacy varied between topics; 70% reported some associated behaviour change and in each case their relatives had been involved in receiving pre-discharge advice. PMID- 2926112 TI - Post-registration nursing courses--one way forward. AB - This paper sets out an alternative method for post-registration nursing courses to the traditional type of 6 or 12 month programmes. The factors involved in precipitating the changes are outlined and the rationale for, and process of, change discussed. The authors believe that shorter, skills based modular programmes--especially at competency (3rd year registered nurse) level--are the key to the future provision of adequate numbers of appropriately skilled registered nurses in the ever increasing number of specialty areas and that these courses must be based upon a strong correlation of theory to advanced clinical practice skills. The paper illustrates this point by describing briefly two of the modular programmes offered at The Queen Elizabeth Hospital, Adelaide. PMID- 2926113 TI - Dying and bereavement. The role of the critical care nurse. AB - The critical care units of today are environments totally dedicated to implementing life saving and life supporting measures. The development of the critical care unit is such that now many critical care units offer specific specialised disease/surgical management e.g. the cardiothoracic unit, transplant centres. As the ability of the critical care units to offer extensive life supportive measures continually improves, the fact is that there is still an increased potential for death to occur in the critical care unit, more than in other acute areas. While the prime function of the critical care staff will always be to support and sustain the life of their patients for whom they care, they also have a responsibility to offer a caring and compassionate level of care to the dying critically ill patient and to ensure that they support the dying patients' relatives in every way that they can. The prospect of death (for the patient), and the actual loss of the patient (for the relatives/medical and nursing staff) can present a number of difficulties for all those involved. These difficulties, which will be identified in the course of the article, may if unresolved predispose to a poor and traumatic bereavement process for the relatives, while the critical care staff may experience possible feelings of frustration, helplessness and low morale. (Caughill, 1976). It is therefore the aim of this article to examine the role of the critical care nurse in caring for the dying patient in the intensive care areas.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2926114 TI - The needs of family members of patients in intensive care units. AB - This study investigated the needs of family members of patients in intensive care units (ICUs) from the families' perspective. A qualitative research methodology was chosen and a 'Grounded Theory' type of approach after Glaser and Strauss was used. The fieldwork comprised informal in-depth interviews with 11 relatives of patients in one general adult intensive care unit in a teaching hospital in the north of England. Previously identified topic areas guided the fieldwork and these were expanded, and new topics included, as appropriate. A tape recorder was used and the interviews were subsequently analysed. Six conceptual categories were developed. The strong theme which emerged was that of 'Retaining Hope'. The study gives some indication of the viewpoint of relatives in ICU and what they perceive to be their major needs. Suggestions for future nursing practice have been presented. PMID- 2926115 TI - Test of the isoallele hypothesis at the mouse first arch (far) locus. AB - We tested the hypothesis that differences in wild-type (+) alleles (isoalleles) at the first arch (far) locus between mouse strains ICR/Bc and BALB/cGaBc are responsible for the partially dominant expression of far in the ICR/Bc genetic background, in contrast to its recessive expression in the BALB/cGaBc background. A similar hypothesis concerning isoalleles has been suggested to explain differences in heterozygote expression in some human genetic diseases but appears not to have been tested directly in mammals. First arch is lethal when homozygous. The dominant effects in ICR/Bc mice include defects in mystacial vibrissa pattern formation and cleft palate. To test the isoallele hypothesis, we made the four appropriate genetic crosses between +/far and +/+ mice between strains. The F1 progeny were scored on day 16 of gestation for defective mystacial vibrissa pattern formation and cleft palate. From all four crosses, approximately 30% of F1 fetuses (i.e., 60% of +/far fetuses) had disrupted mystacial vibrissa patterns, and only one fetus had cleft palate. The fact that all crosses produced approximately equal rates of defective progeny disproves the isoallele hypothesis for far. Therefore, differences between strains in alleles at other loci (modifier loci) must cause the differences in heterozygote (+/far) expression. This genetic design can be used for other mutations with strain differences in heterozygote expression to test the importance of isoalleles in mammals. PMID- 2926116 TI - Inbreeding, coancestry, and covariance between relatives for X-chromosomal loci. AB - Knowledge about the relationships between relatives for X-chromosomal loci is necessary to compute genetic variances and covariances for the genetic evaluation of individuals for economically important traits in livestock and poultry. Using a unified approach, we derived explicitly the coefficient of inbreeding for individuals and the coefficient of coancestry between collateral and lineal relatives of the same or different sex, assuming that the male is heterogametic and the female is homogametic. Collateral relatives include full sibs, paternal and maternal half-sibs, paternal and maternal single first cousins, and double first cousins. Lineal relatives include parent-offspring, paternal and maternal grandparent-grandoffspring, and aunt- or uncle-niece or -nephew. We also defined additive and dominance relationships to compute genetic covariance between relatives, assuming random mating equilibrium, and clarified misinterpretations and corrected errors in the literature. Our results are also applicable to organisms that have few autosomal loci, such as Drosophila, in which X chromosomal loci can account for a large amount of genetic variance, and to haplodiploid organisms, such as the honeybee, in which the entire genome is equivalent to being X-chromosomal. PMID- 2926117 TI - High-resolution G-banded karyotype and idiogram of the goat: a sheep-goat G banded comparison. AB - An elongated G-banded karyotype and idiogram of the domestic goat (Capra hircus) is presented. Sheep (Ovis aries)-goat comparison suggests the terminal light band (Xq 2 9) present in the goat is absent in the sheep. PMID- 2926119 TI - Systemic fungal infections: diagnosis and treatment II. PMID- 2926118 TI - Two recessive rex coat mutants in the guinea pig. AB - Two rex type coat mutants of the guinea pig were found to display monogenic recessive inheritance at independent loci. The mutant alleles were designated rex (rx) and waved (wv). Both genes modify the normal smooth coat to a more upright, somewhat unkempt pelage. Macroscopically, the two rexes are scarcely distinguishable. Microscopically, however, small differences are apparent in the degree of coat modification. The hairs of rex show a greater curvature than normal and have irregular secondary bends and twists and variable diameter; so do those of waved, but to a lesser degree. The vibrissae of rex are curved or bent and may break off; those of waved are a mixture of straight, curved, and bent hairs. PMID- 2926120 TI - Detection of phosphoenolpyruvate and ribulose 1,5-bisphosphate carboxylase transcripts in maize leaves by in situ hybridization with sulfonated cDNA probes. AB - This report outlines an efficient in situ hybridization method for locating specific mRNAs in tissue cryosections using sulfonated cDNA probes. The method involves chemical modification of DNA probes by insertion of a sulfone radical on cytosine residues, which generates a specific epitope. Sulfonated DNA is then detected by using indirect immunochemical procedure. Alternatively, antibodies conjugated to fluorescein or to alkaline phosphatase were used for mRNA detection. In situ hybridization was developed to study aspects of mesophyll and bundle sheath cell differentiation in maize leaves. Our results indicate that phosphoenolpyruvate carboxylase (PEP C) mRNA is restricted to mesophyll cells, and the nucleus-encoded mRNA of the small subunit (SSU) ribulose 1,5-bisphosphate carboxylase (RuBP C) is limited to the cytosol of bundle sheath cells. Thus, using in situ hybridization, we have demonstrated that the differential distribution of PEP C and RuBP C proteins in the two cell types also reflects the location of their mRNAs. These data imply either a tissue-specific transcriptional regulation or a selective mRNA degradation. PMID- 2926121 TI - Binding and uptake of pulmonary surfactant protein (SP-A) by pulmonary type II epithelial cells. AB - A glycoprotein of Mr 26-36,000 (SP-A) is an abundant phospholipid-associated protein in pulmonary surfactant. SP-A enhances phospholipid reuptake and inhibits secretion by Type II epithelial cells in vitro. We have used two electron microscopic cytochemical methods to demonstrate selective binding and uptake of SP-A by rat pulmonary Type II epithelial cells. Using an immunogold bridging technique, we showed that SP-A binding was selective for Type II cell surfaces. Binding was dose dependent and saturable, reaching maximal binding at approximately 10 ng/ml. On warming to 23 degrees C, SP-A binding sites were clustered in coated pits on the cell surface. To characterize the internalization and intracellular routing of SP-A, we used the biotinyl ligand-avidin-gold technique. Biotinyl SP-A was bound by rat Type II epithelial cells as described above. On warming, biotinyl SP-A was seen in association with coated vesicles and was subsequently located in endosomes and multivesicular bodies. Biotinyl SP-A gold complexes were seen in close approximation to lamellar bodies 10-60 min after warming. Binding of biotinyl SP-A was inhibited by competition with unlabeled SP-A. These results support the concept that Type II epithelial cells bind and internalize SP-A by receptor-mediated endocytosis. This newly described uptake system may play a role in the recycling of surfactant components or mediate the actions of SP-A on surfactant phospholipid secretion. PMID- 2926122 TI - Immunocytochemical localization of S-100b protein in degenerating and regenerating rat sciatic nerves. AB - We studied the cellular and subcellular distribution of S-100b protein in normal, crushed, and transected rat sciatic nerves by an immunocytochemical procedure. In uninjured nerves, S-100b protein was restricted to the cytoplasm and membranes of Schwann cells, with no reaction product present in the nucleus or in axons. Similar images were seen from the first to the thirtieth day after the crush in activated Schwann cells during the degeneration period, i.e., up to the seventh post-lesion day, and in normal Schwann cells reappearing during the regeneration period, i.e., after the seventh post-lesion day, in the zone of the crush and proximal and distal to it. By the technique employed, there seemed to be no differences in the intensity of the immune reaction product in normal and activated Schwann cells. Also, similar images were seen in the proximal stump of transected nerves. Only a slight S-100b protein immune reaction product could be observed in the rare activated Schwann cells present in the distal stump around the seventh post-lesion day, the majority of cell types being represented by fibroblasts and elongated cells at this stage and thereafter. By immunochemical assays, similar results as those presented here have been reported and interpreted as indicative of the presence of S-100 protein in axons or, alternatively, of axonal control over expression of S-100 protein in Schwann cells. Our immunocytochemical data clearly show that the strong reduction in the S-100 protein content of the distal stump of transected nerves is owing to the paucity of Schwann cells and to the decrease in the S-100 protein content of these cells, rather than to degeneration of axons. PMID- 2926123 TI - Fiber type-specific distribution of M-band proteins in chicken muscle. AB - The functions of two myofibrillar proteins, myomesin (Mr 185,000) and M-protein (Mr 165,000), associated with the M-band are as yet unknown. To extend our knowledge of these proteins, we have examined chicken striated muscles with fast and slow contractile properties, e.g., pectoralis major, PLD, ALD, medial adductor, and lateral adductor, to determine the expression and isoform composition of myomesin and M-protein in various muscles and fiber types. The high molecular weight M-band proteins were characterized and quantitated using monoclonal antibodies in immunoblotting and double-antibody sandwich ELISA. Fiber specificity was determined by immuno- and enzyme histochemistry. In addition to the previously reported Mr 195,000 and 190,000 isoforms of myomesin in heart [Grove et al. (1985): J Cell Biol 101:1431], the Mr 185,000 myomesin in skeletal muscles may represent different isoforms in fast and slow muscles on the basis of distinctive degradation patterns. M-protein has the same molecular weight in striated chicken muscles and degradation patterns indicate only one isoform. The low quantities of M-protein in slow muscles were shown to be due to the absence of M-protein in two of the generally recognized slow fiber types, types I and III. Thus, M-protein was present only in fast type II fibers, whereas myomesin was ubiquitous in all fiber types. Whatever the causal relationship, M-protein appears to function in fast motor units composed of type II fibers. PMID- 2926124 TI - Immunogold labeling method for Mycobacterium leprae-specific phenolic glycolipid in glutaraldehyde-osmium-fixed and Araldite-embedded leprosy lesions. AB - Phenolic glycolipid (PGL)-I, a Mycobacterium leprae-specific antigen currently used for serodiagnosis of preclinical leprosy, has thus far not been localized subcellularly in leprosy bacilli and their host cells. In this study, we developed an immunogold-labeling technique for qualitative identification of PGL I sites in glutaraldehyde-osmium-fixed and Araldite-embedded M. leprae and host macrophages in human skin biopsies. Such "hard-fixed," plastic-embedded skin and nerve biopsies from patients with varying cell-mediated immunity to leprosy are amply available worldwide. Our method involves etching of plastic sections with H2O2, incubation with swine serum to eliminate nonspecific labeling, and long (22 hr) incubation at room temperature with monoclonal antibodies to PGL-I. Gold labeling was seen predominantly on cell walls of M. leprae, in vacuolar spaces of bacillated phagolysosomes, and occasionally on the cytoplasm and cell membrane of M. leprae. Host macrophage cytoplasm was labeled very infrequently. This technique allows studies on possibly persisting antigenic PGL-I in multibacillary leprosy patients during or after multidrug therapy. The method may also prove useful for subcellular localization of specific bacterial lipids in other mycobacterial diseases, including tuberculosis. PMID- 2926125 TI - Effects of acute doses of sodium fluoride on the morphology and the detectable calcium associated with secretory ameloblasts in rat incisors. AB - Fluoride in high concentrations is known to have an adverse effect on the formation of enamel. The effect of a single injection of two concentrations of sodium fluoride on inner enamel secretory ameloblasts was investigated morphologically by electron microscopy and functionally by assessing the location and relative amount of available calcium, using the potassium pyroantimonate method. The results showed that acute doses of fluoride interfere with the normal function of secretory ameloblasts. The increase in the population of lysosome like structures observed after fluoride administration is suggestive of defects in the synthetic pathway. Concomitant with the effect of fluoride on secretory ameloblasts is an inhibition of enamel formation, resulting in incomplete enamel rods and leaving large remnants of Tomes' processes buried in the enamel. The distribution of the calcium pyroantimonate deposits found tends to support the concept of calcium traveling between the cells to the enamel. Acute doses of fluoride also reduce the amount of calcium available for complexing with pyroantimonate in the intercellular region. PMID- 2926126 TI - Calbindin-D immunolocalization in developing chick thyroid: a light and electron microscopic study. AB - Antiserum to calbindin-D, a 28 KD vitamin D-dependent calcium binding protein, was used to localize the protein immunocytochemically in developing chick thyroid by both light and electron microscopy. The protein first appeared in future follicular cells of developing thyroid tissue from 8-day-old embryos. The number of calbindin-D-containing cells increased rapidly to a near-plateau level at day 10; this concentration was sustained until day 15, and then declined to an undetectable level just before hatching. The protein was distributed throughout organelle-free areas of the follicular cell cytoplasm and extended into the nucleus; it was not present in the follicular colloid. Comparison of the time course of changes in calbindin-D content with known differentiative changes taking place in follicular cells suggests that the protein may function in some yet to be determined mechanism related to normal development of the thyroid. PMID- 2926127 TI - Tissue distribution of antileukoprotease and lysozyme in humans. AB - We studied the distribution of the proteinase inhibitor antileukoprotease (ALP) and lysozyme (LSZ) in normal human tissues by use of an immunohistochemical technique. ALP could be demonstrated in a variety of healthy tissues, generated by secretory cells in lacrimal, respiratory, proximal digestive, and genital glands, but not in the urinary tract, endocrine glands, or the hematological system. In lung, part of the non-ciliated cell population in membranous bronchiolar epithelium, as well as in respiratory bronchioles, stained positively for the inhibitor. The distribution of ALP and LSZ was parallel in most but not all of the tissues examined. The distribution of ALP around most of the external orifices of the human body is discussed in relation to its possible local physiological role in defense against inflammatory reactions. The widespread parallel distribution of LSZ, a bacteriolytic agent, suggests a complementary role to ALP in local defense. PMID- 2926128 TI - Light and electron microscopic immunolocalization of rat submandibular gland mucin glycoprotein and glutamine/glutamic acid-rich proteins. AB - We studied the subcellular localization of two major secretory products of adult rat submandibular gland (RSMG), blood group A-reactive mucin glycoprotein and glutamine/glutamic acid-rich protein (GRP), by light and electron microscopic immunocytochemistry. The structure of the major neutral oligosaccharide of the mucin was shown to be: GalNAc alpha 1,3(Fuc alpha 1,2)Gal beta 1,3GalNAc. A mouse monoclonal antibody (1F9) with specificity for blood group A determinants was prepared against the mucin. The antibody recognized a single band of approximately 114 KD on Western blots of RSMG extract. A previously characterized monoclonal antibody (59) against GRP (Mirels et al.: J Biol Chem 262: 7289, 1987) reacted with a doublet of 45-50 KD on Western blots of extraparotid saliva. Immunofluorescence and immunoperoxidase staining of cryostat sections of RSMG with anti-mucin antibodies and anti-GRP antibodies revealed reactivity in acinar cells of the gland. No specific labeling was seen in duct cells of RSMG or in mucous acinar cells of the adjacent sublingual gland. Post-embedding immunogold labeling of thin sections of glutaraldehyde-fixed RSMG with anti-mucin showed strong labeling of the Golgi apparatus and secretory granules of acinar cells. Gold particles were seen mainly over electron-lucent areas of the granules. No labeling occurred over the endoplasmic reticulum. The labeling pattern with the anti-GRP antibodies was similar, except that both electron-dense and -lucent areas of the granules were labeled, and the endoplasmic reticulum was reactive. Double labeling with two different sizes of gold particles showed that both mucin and GRP co-localized in the same granules. Pre-absorption of the antibodies with their respective antigens eliminated immunolabeling of the acinar cells. These antibodies will be useful in studies of cell differentiation in RSMG and of synthesis, processing, and packaging of RSMG secretory products. PMID- 2926129 TI - Blotting method using nitrocellulose sheets for immunohistochemical detection of soluble thyroid antigens. AB - We introduce a new method for immunofluorescence detection of soluble material by blotting unfixed antigens onto nitrocellulose (NC) sheets. Human thyroid sections cut with a cryostat were mounted on NC sheets instead of glass slides and were air-dried. They were stained by immunofluorescence techniques, using autoantibodies to thyroid antigens obtained from 13 patients with chronic thyroiditis. The structures of the follicle lumen and epithelium were visualized by localization of specific antibodies. This tissue-blotting method sensitively detected soluble antigens, such as thyroglobulin, which are difficult to detect by conventional methods. PMID- 2926130 TI - Binding of biotin to hepatitis B surface antigen: a possible pitfall in immunohistochemistry. AB - We report on the binding of biotin, and hence of biotinylated antibodies and lectins, to ground glass hepatocytes and liver cell membranes in chronic hepatitis B viral infection. This binding is of low affinity, and was proved to be directed at the hepatitis B surface antigen, presumably at its disulfide bonds. To avoid false-positive results, this affinity should be considered in the interpretation of immunohistochemical stainings of hepatitis B virus-infected liver tissue with biotinylated reagents. PMID- 2926131 TI - Exogenous glucocorticoid eliminates or reverses circadian blood pressure variations. AB - The effect of glucocorticoid on circadian variations of blood pressure was examined. In untreated patients with essential hypertension, a clear nocturnal fall in blood pressure and heart rate was observed and this was unaffected by combined treatment with antihypertensive drugs. The circadian blood pressure variation in patients with chronic glomerulonephritis (CGN) not receiving glucocorticoid treatment was essentially the same as that in patients with essential hypertension. In both groups there was a positive correlation between blood pressure and heart rate. On the other hand, in patients with CGN and systemic lupus erythematosus (SLE) who were treated with glucocorticoid, there was no nocturnal fall in blood pressure, and often a significant rise. In these patients the blood pressure was lowest in the afternoon and began to rise from then, and during the night, attaining a peak level in the morning. Despite this changed pattern of blood pressure variations, the heart rate in these patients was clearly reduced at night. In 10 patients with CGN and SLE, circadian rhythm of blood pressure and heart rate was examined before and during treatment with prednisolone (40.2 +/- 17.0 mg/day for 58.0 +/- 19.4 days, mean +/- s.d.). Prednisolone abolished the nocturnal fall of blood pressure, while the nocturnal fall of heart rate remained. There was no correlation between blood pressure and heart rate in patients with glucocorticoid treatment. These results suggest that the circadian blood pressure variation is influenced by the hypothalamo-pituitary adrenal axis, probably through its action on the autonomic nervous system. PMID- 2926132 TI - Home blood pressure-measuring devices: a comparative study of accuracy. AB - Self monitoring of blood pressure by hypertensive patients has been shown to be of value and is increasingly popular. However, the accuracy and ease of use of at least some of the equipment for home use is questionable. We tested 23 pairs of home blood pressure devices, using static methods, trained observers with volunteer subjects and hypertensive patients. Eleven (48%) of the 23 pairs of devices tested were found inconsistent with their duplicate and failed the standards for automated devices of the Association for the Advancement of Medical Instrumentation. Several of the devices, all sold for home use by lay people, contained no instructions whatsoever and even patients using those machines with instructions required further training in blood pressure measurement. While home blood pressure monitoring is useful in certain circumstances, care must be taken in the choice of device, and training is required for all devices. PMID- 2926133 TI - Structural changes vary along individual arterioles in deoxycorticosterone acetate hypertensive rats. AB - The variability of structural changes along individual arterioles in deoxycorticosterone acetate (DOCA) hypertensive rats was measured by coefficients of variation of: (a) serial lumen diameters along microfil casts of individual mesenteric arterioles; and (b) wall and lumen indices in serial histological cross-sections along individual renal arterioles. The mean lumen diameter of third-order mesenteric arterioles decreased with increasing duration of hypertension. There was increased variability of lumen diameter along lengths of DOCA arterioles, the coefficient of variation at 10 weeks DOCA treatment being 20.2 +/- 0.6% compared to 9.2 +/- 0.2% in controls (P less than 0.001). Medial area to internal elastic lamina (IEL) radius ratio of renal arterioles was increased in DOCA rats compared with control rats (P less than 0.025) and its variability along individual arterioles expressed as the coefficient of variation was 31.70 +/- 3.87% in DOCA rats compared with 15.29 +/- 1.72% in controls (P less than 0.005). The observed increase in variability of lumen diameter and medial area along short lengths of individual arterioles in DOCA hypertensive rats indicates that hypertensive structural changes are probably not directly related to local blood pressure. We suggest that irregular functional vasoconstriction in hypertensive rats could account for this distribution of structural changes. PMID- 2926134 TI - The effect of withdrawing antihypertensive therapy: a review. PMID- 2926135 TI - Influence of complement C5 and V beta T cell receptor mutations on susceptibility to collagen-induced arthritis in mice. AB - SWR/J mice are resistant to collagen-induced arthritis (CIA) despite having a susceptible H-2q haplotype. We have earlier demonstrated the possible role of the V beta TCR mutation of SWR in the resistance to CIA. To investigate the influence of the C5 deficiency of SWR in this resistance, crosses were made between SWR and A/J (C5 deficient, TCRwild, H-2a), and between SWR and C3H.A (C5 sufficient, TCRwild, H-2a). Upon immunization with bovine type II collagen in adjuvant, there was a similar incidence and severity of arthritis in H-2q-bearing mice in the back-crosses A x (SWR x A) ad C3H.A x (SWR x C3H.A). The absence of hemolytic complement was confirmed in the arthritic A x (SWR x A) back-cross mice by standard SRBC hemolytic assays. In addition C57L (H-2b) mice, which were C5 sufficient but had a V beta TCR deletion mutation similar to SWR, could not complement for CIA susceptibility in H-2q-bearing C57L x (SWR x C57L) back crosses and in (C57L x SWR)F2 hybrids. These studies show that complement C5 does not play a significant role in CIA susceptibility, and further implicate the V beta TCR mutation in the resistance to CIA in SWR mice. PMID- 2926136 TI - Binding of human C-reactive protein to mouse macrophages is mediated by distinct receptors. AB - Human C-reactive protein (CRP) is known to activate mouse macrophages (M phi) to a tumoricidal state and to serve as an opsonin for M phi. Therefore, cell surface receptors for CRP on mouse M phi were characterized and their relationship to the IgG FcR determined. The specific binding of 125I-CRP to resident or elicited mouse M phi was saturable, reversible, and involved both a high and a low affinity receptor population. Binding of CRP to the mouse M phi cell lines PU5 1.8 and J774 was nearly identical to that observed with peritoneal M phi. The high affinity receptor population had a calculated K of 10 nM and a receptor density of approximately 10(5) sites per cell. Mouse Ig of the IgG2a, IgG2b, or IgG1 isotypes inhibited binding of 125I-CRP to PU5 1.8 cells at concentrations five-fold greater than that of the homologous ligand. In the converse experiment, unlabeled CRP failed to inhibit specific binding of 125I-labeled IgG2a, IgG2b or IgG1. Isolation of CRP binding proteins from surface iodinated PU5 1.8 cells by ligand-affinity chromatography or chemical cross-linking yielded a major protein band of 57 to 60 kDa which appeared to be distinct from the IgG1/IgG2b FcR (FcR II) membrane proteins. Removal of radiolabeled IgG2b/IgG1 binding membrane proteins by affinity chromatography did not remove CRP-binding proteins. The rat mAb 2.4G2 which inhibits binding of radiolabeled mouse IgG2b, did not inhibit the binding of CRP. A rat polyclonal antiserum to CRP-binding membrane proteins of PU5 1.8 cells inhibited 125I-CRP binding, but not 125IgG2b binding. The rat polyclonal antibody reacted with two 57 to 60 kDa membrane proteins from PU5 1.8 cells that appear to be of a similar size on Western blots. The 125I-CRP was internalized via endosomes and intact CRP subunits could be detected intracellularly. The findings suggest that binding of CRP occurs through a receptor that is distinct from the IgG FcRs, but that CRP-R activity may be influenced by an association with an IgG FcR. PMID- 2926137 TI - IgA-induced eosinophil degranulation. AB - Eosinophils play an important role as effector cells in allergic, parasitic, and other conditions. The mechanism(s) by which eosinophils mediate their effector functions was studied by incubation of human normodense eosinophils with Sepharose beads coupled to various Ig isotypes as targets. Controls included eosinophils incubated alone or incubated with uncoated beads, human serum albumin , or OVA-coated beads. An eosinophil granule protein, the eosinophil-derived neurotoxin (EDN), was measured as an indicator of eosinophil degranulation. Eosinophils released eosinophil-derived neurotoxin when incubated with Sepharose beads coupled to Ig of the IgG or IgA isotypes, as well as IgA-Fc fragments. Mixtures of IgG and IgA on beads did not act synergistically. Secretory IgA (sIgA) provided the most potent signal for eosinophil degranulation and was two to three times more potent than IgG. Furthermore, 2 to 17% of the normodense eosinophils bound to IgG- or IgA-coated beads, whereas 24 to 27% of the eosinophils bound to sIgA-coated beads. Thus, sIgA may be the principal Ig mediating eosinophil effector function at mucosal surfaces in helminth infections and hypersensitivity diseases, especially bronchial asthma. PMID- 2926139 TI - The mast cell-committed progenitor. II. W/Wv mice do not make mast cell-committed progenitors and S1/S1d fibroblasts do not support development of normal mast cell committed progenitors. AB - We have previously reported that the population of mesenteric lymph node cells from normal BALB/c mice infected 14 days with the rodent nematode Nippostrongylus brasiliensis (Nb-MLN) contains a nongranulated mast cell-committed progenitor (MCCP) which does not require IL-3 for proliferation and differentiation if either a fibroblast monolayer or soluble factors produced by monolayers of 3T3 fibroblasts or embryonic skin are present in the culture. When Nb-MLN were cloned in a methylcellulose culture system using fibroblast conditioned medium as the only source of growth factors, numerous colonies of pure mast cells developed. We wished to determine whether the mast cell deficiency of W/Wv or S1/S1d mice could be explained by the failure of these mice to make either the MCCP or the factor to support proliferation and differentiation of the MCCP. We found that Nb-MLN from W/Wv mice were only able to produce mast cell colonies in response to a source of IL-3 such as conditioned medium from pokeweed mitogen-stimulated spleen cells (CM), and cultures given fibroblast conditioned medium as the only source of growth factors did not produce mast cell colonies. In contrast, Nb-MLN from mast cell deficient S1/S1d mice developed many mast cell colonies in methylcellulose cultures supplemented with either fibroblast conditioned medium or conditioned medium from PWM-stimulated spleen cells. These data suggest that S1/S1d mice but not W/Wv mice produce the mast cell progenitor that responds to fibroblast conditioned medium. To determine if mast cell deficient mice make the fibroblast derived factors that support development of the MCCP, monolayers were prepared from skin connective tissues of S1/S1d and W/Wv mice and Nb-MLN from normal BALB/c mice were cloned in the presence of conditioned medium from these monolayers. Fibroblast conditioned medium from monolayers prepared from W/Wv but not S1/S1d mice supported development of numerous mast cell colonies. Taken together, these data demonstrate that W/Wv mice are incapable of producing normal MCCP whereas S1/S1d fibroblasts fail to produce the appropriate factor to support the MCCP. In accordance with these data, a candidate for the gene product of each of these mutant alleles is discussed. PMID- 2926138 TI - Biologic activity of a C2-derived peptide. Demonstration of a specific interaction with guinea pig lung tissues. AB - A synthetic peptide derived from the carboxy terminus of C2b has been investigated for its ability to induce the contraction of guinea pig lung parenchymal strips. This peptide is known to enhance vascular permeability in guinea pig and human skin, and to induce contraction of estrous rat uterus. This C2 peptide (C2 207-223) is active from 5 x 10(-5) M to 5 x 10(-4) M and is not tachyphylactic to itself. No cross-activity between C2 207-223 and C5a or C3a could be demonstrated. C2 207-223 is not inhibited by antihistamines or cyclooxygenase inhibitors. These data indicate that the peptide exerts its action via a mechanism distinct from those of the C3a and C5a anaphylatoxins. PMID- 2926140 TI - Differential effects of liposome-incorporation on liver macrophage activating potencies of rough lipopolysaccharide, lipid A, and muramyl dipeptide. Differences in susceptibility to lysosomal enzymes. AB - We investigated the in vitro activation of rat liver macrophages to a tumor cytotoxic state with muramyl dipeptide (MDP), rough LPS (Re-LPS) and lipid A in both a free and liposome-encapsulated form. The tumor cytotoxic state of the liver macrophages was determined with a [methyl-3H]thymidine release assay using C26 colon adenocarcinoma cells as target cells. As was shown previously, the encapsulation of MDP within multi-lamellar phospholipid vesicles greatly enhanced the activating potency of the drug; by contrast, encapsulation of Re-LPS or lipid A significantly reduced the activation of macrophages as compared to the free form of these agents. At a dose of 1 ng of free Re-LPS per ml a significant induction of tumor cell lysis was observed whereas a maximal level was obtained at a concentration of approximately 10 ng/ml. By encapsulation of Re-LPS in liposomes the activating potency diminished 20- to 100-fold. The minimal concentration required to induce detectable macrophage activation with free lipid A was 10 ng/ml, while liposome-encapsulated lipid A did not induce any detectable tumor cell lysis up to a concentration of 200 ng/ml. After a 1-h pre-incubation with a lysosomal fraction from rat liver at pH 4.8, the macrophage-activating potency of Re-LPS and lipid A was diminished by up to 95% whereas MDP remained fully active under these conditions. We conclude that, due to endocytic uptake of liposome-incorporated Re-LPS and lipid A and subsequent intralysosomal degradation, these immunomodulators are inactivated with respect to their potency to activate liver macrophages to tumor cytotoxicity. PMID- 2926141 TI - Functional heterogeneity of macrophage precursor cells from spleen of Leishmania donovani-infected and untreated mice. AB - We recently described the bone marrow-derived macrophage precursor, which is able to spontaneously and extracellularly kill protozoa of the genus Leishmania. These nonadherent, nonphagocytic macrophage precursor cells are present in the spleen of healthy mice only in a small quantity. However, high numbers of proliferating macrophage precursors are isolated from the spleen of Leishmania donovani infected mice. Macrophage precursors from spleens of diseased animals are able to kill spontaneously the promastigote as well as the amastigote form of L. donovani. The mechanism of the spontaneous leishmanicidal activity of macrophage precursor cells derived from spleens of L. donovani-infected mice was investigated. This effector function could be defined in part as an antibody dependent cellular cytotoxicity. In addition we assessed the role of CSF-1 containing L cell-conditioned supernatant at the leishmanicidal activity of these immature cells of the macrophage lineage. For that purpose, nonadherent spleen cells from healthy mice were cocultivated with this CSF-1-containing medium for 4 days. These in vitro proliferated macrophage precursor cells from untreated mice showed an increased leishmanicidal activity. Thereby we established a further activation mechanism for proliferating splenic macrophage precursor cells responsible for the observed killing of L. donovani pro- and amastigotes. The spontaneous cytotoxicity of macrophage precursors from spleens of L. donovani diseased animals is thus defined as a cooperative effect of antibody-dependent cellular cytotoxicity and Macrophage-CSF activation. PMID- 2926143 TI - Natural antibacterial activity against Salmonella typhi in human cord blood. AB - Cord blood mononuclear cells from normal human newborns possess natural antibacterial (NA) activity against Salmonella typhi, as assessed by an in vitro test. NA activity was significantly higher than that observed in PBMC from normal adult donors. Using fractionation on nylon wool and Percoll gradient or C dependent killing with mAb, it was found that cells of the monocyte-macrophage series and CD4+ T lymphocytes were capable of exerting NA activity in newborns, in contrast with results obtained in adults, where the effector cell was a CD4+ T lymphocyte. The capability of expressing NA activity by CD4+ T lymphocytes from cord blood was also confirmed by flow cytometry sorting. Pretreatment of cord blood mononuclear cells with F(ab')2 fragments against human IgG, but not against human IgA, abrogate the NA activity. Furthermore, human IgA anti-S. typhi cannot arm CD4+ lymphocytes in cord blood. Thus it can be suggested that in newborns, the immune system still being immature, NA activity might be the expression of a mechanism of defence against infections, acting as antibody-dependent cellular cytotoxicity expressed by monocytes and CD4+ T lymphocytes armed with preexisting maternal IgG antibodies. This differs from NA activity of adults which is only mediated by CD4+ T lymphocytes armed by IgA. PMID- 2926142 TI - Effect of breast feeding on the development of anti-idiotype antibody response to F glycoprotein of respiratory syncytial virus in infant mice after post-partum maternal immunization. AB - Groups of lactating BALB/c mice were immunized in the immediate postpartum period with high doses of mAb (Ab-1) to the F-glycoprotein (F-gp) of respiratory syncytial virus (RSV). This antibody possessed neutralizing activity against the whole virus. The immune response to F-gp was studied in the breast feeding infant mice of such mothers at regular intervals before and after weaning. All infant mice exhibited anti-F-gp activity in serum, which was detected until 6 wk of age. Splenic cells of such breast feeding infant mice collected after weaning exhibited in vitro synthesis of antibody against Ab-1, the antibody previously used for maternal immunization. Subsequent immunization with homologous purified RSV F-gp resulted in a booster response for IgG, IgM, and plaque-neutralizing antibody to the immunizing RSV protein and to the whole virus in the infants primed via breast feeding. The enhanced antibody response was specific for the antigenic epitopes of the virus protein recognized by the monoclonal antibody used for maternal immunization. Similar booster effect was seen in control infants of nonimmunized mothers who were immunized with a polyclonal Ab-2 prepared by repeated immunization with Ab-1 in DBA/2 mice. These data demonstrate induction of RSV-specific anti-idiotype antibody in the neonates via the process of breast feeding, secondary to maternal immunization after the delivery of the neonate. Use of idiotypic vaccines in the mother and the transfer of RSV-specific idiotypes may offer an alternate approach to the development of effective immunoprophylaxis for RSV infection in early infancy. PMID- 2926144 TI - Carrier-bound synthetic peptides. Use as antigen in HIV-1 ELISA tests and in antiserum production. AB - Chemically synthesize carrier-bound peptides have been used as antigens in diagnostic test systems (ELISA) and for raising antipeptide-specific antisera. The method does not require prior cleavage of the peptides from the support used for the solid-phase synthesis. Using the same resin for both the synthesis and the subsequent applications it was possible to avoid expensive and time-consuming purification procedures and artificial recoupling to solid supports. A quick and specific ELISA-based diagnostic test system for HIV-specific antipeptide antibodies in human sera was established. In addition the carrier-bound peptides were shown to be potent antigens for raising antibodies in animals. PMID- 2926145 TI - Production and characterisation of antibodies to vanillylmandelic acid. AB - Antibodies were raised to the catecholamine metabolite vanillylmandelic acid (VMA). The side chain was protected and, after derivatisation through the 4 phenolic hydroxyl group, the hapten was coupled to KLH and the resultant conjugate deprotected. Sheep immunised with this immunogen responded with specific, high titre antibodies to VMA as assessed using a fluorescent label. Cross-reaction of the antiserum from one of the sheep was minimal, being under 1% with all naturally occurring related compounds tested. This report is the first to describe an effective antiserum for VMA which will permit measurement over the normal range in urine. PMID- 2926146 TI - A two-site sandwich immunoradiometric assay of squirrel monkey (Saimiri sciureus) IgM using monoclonal antibodies. AB - Nine hybrid clones secreting antibodies to squirrel monkey (Saimiri sciureus) IgM were produced and two of these (1F1G5 and 5H11B3) were selected for further studies. These non-precipitating monoclonal antibodies reacted with two distinct repetitive antigenic determinants, probably of the conformational type, only present on the native or SDS-denatured IgM molecule. Reduction of the pentamer with 2-mercaptoethanol led to complete destruction of the corresponding epitopes. 1F1G5 antibodies from ascitic fluids were used in the purification of monkey IgM by affinity chromatography. The characteristics of 1F1G5 and 5H11B3 MAbs permitted the development of a solid-phase two-site immunoradiometric assay for the measurement of IgM levels in serum specimens taken from healthy animal donors of both sexes. PMID- 2926147 TI - Direct immunization with synthetic peptidyl-polyamide resin. Comparison with antibody production from free peptide and conjugates with carrier proteins. AB - An 11-amino acid residue peptidyl-linkage agent-polyamide resin complex was synthesized by the fluorenylmethyloxycarbonyl (Fmoc)-polyamide solid-phase system. Mice were immunized with the free peptide, peptidyl-resin and peptide coupled to the carrier proteins ovalbumin (Ova) and keyhole limpet haemocyanin (KLH). The immunogenicity of these materials was assessed by measurement of the capacity of the various antisera to bind the peptide in an enzyme-linked immunosorbent assay (ELISA). The peptidyl-resin exhibited enhanced immunogenicity compared to the free peptide. It is suggested that the time needed for screening for immunogenicity of large numbers of synthetic peptides thus be greatly shortened by using peptidyl-resins for immunization. This method eliminates laborious cleavage of peptide from resin, purification, coupling to carrier and the difficulties of handling peptides of low solubility. PMID- 2926148 TI - Use of lipophilic fluorescent probes for the isolation of hybrid cells in flow cytometry. AB - Flow cytometry was used for the isolation of hybrid cells immediately after fusion. Precursor cells were stained by two lipophilic fluorescent probes: perylenoyl-labeled triglyceride (perylenoyl-TG, green fluorescence, 520 nm) and rhomdaminyl-labeled triglyceride (rhodaminyl-TG, red fluorescence, greater than 580 nm). Since the maximum emission of perylenoyl-TG coincides with the maximum absorbance of rhodaminyl-TG, the two fluorescent dyes form an effective donor acceptor pair. Cells stained by perylenoyl-TG (0.25-1 microgram/ml) at the excitation wavelength of 457 nm displayed high intensity of fluorescence in the green region (520 nm), and low intensity of fluorescence in the red region (greater than 580 nm). Using the same conditions, cells that were stained by rhodaminyl-TG displayed a low intensity of fluorescence in both regions. When cells were simultaneously labeled by perylenoyl-TG and rhodaminyl-TG (used in a concentration ratio of 1:10, respectively) essentially total energy transfer was observed, and the cells exhibited a high intensity of red fluorescence. After the fusion of cells which had been separated stained by perylenoyl-TG and rhodaminyl TG, the hybrid cells containing the two fluorescent probes had a high intensity of red fluorescence. Resonance exitation energy transfer between the two fluorescent dyes permits effective sorting of hybrid cells by flow cytofluorometry. PMID- 2926149 TI - Antibodies raised against denatured DNA bind to double-stranded DNA. AB - Antibodies raised against denatured DNA complexed with methylated bovine serum albumin have been reported to react with ssDNA but not with dsDNA. Using a highly sensitive avidin-biotin microELISA, we report that such antibodies also bind to dsDNA. Antibodies which reacted with ssDNA and dsDNA were found to be of IgG type. The antibodies did not react with tRNA and rRNA. The binding of antibodies to dsDNA was partially inhibited by individual deoxyribonucleotides. ssDNA as well as dsDNA inhibited the binding of antibodies to dsDNA. The binding of these antibodies to supercoiled and relaxed forms of pBR322 DNA was demonstrated by gel retardation assay. The cross-reaction with ssDNA was observed even after affinity purification on native DNA-cellulose. The antibodies were also shown to bind to poly(dA-dT).poly(dA-dT). PMID- 2926150 TI - A new compact and cell dense continuous culture system. AB - A new compact and cell dense continuous culture system was developed. The system consisted of a culture bag, which had two compartments separated by a semipermeable membrane, and an external rotator. Cells were cultured in the inner compartment with medium containing serum or the necessary growth factors. The outer compartment was filled with medium without serum or growth factors. The concentration of cells in culture was normally in the order of 10(7). Due to the large number of cells, sufficient carbon dioxide was produced so that use of a CO2 incubator was unnecessary. The medium in the outer part was frequently changed, but no medium changes were necessary in the inner bag. Using this system, a concentrated yield of antibody as well as a large number of cells could be obtained. PMID- 2926151 TI - Development of an ABO-ELISA for the quantitation of human blood group anti-A and anti-B IgM and IgG antibodies. AB - An indirect ELISA system was designed for quantitation of human blood group A and B IgM and IgG antibodies. The capturing antigens are blood group substance A or B used to sensitize polystyrol microtiter plates. Bound anti-A or anti-B antibodies are revealed either directly, by development with polyclonal anti-human immunoglobulin class-specific conjugate or with more avid mouse monoclonal anti human isotype antibodies revealed in turn by goat anti-mouse conjugate. Reproducibly, 100 ng specific anti-A IgG provided for a significant above background signal of 0.2 at OD405 and 15 serum samples had a mean content of 3.98 +/- 8.74 micrograms (mean +/- 2 SD) (range: 0.305-12.62) of specific anti-A IgG/g total IgG. Thus one molecule specific anti-A IgG is found per 7.9 X 10(4)-3.2 X 10(6) total IgG molecules. Statistical correlations were significant between anti A IgG levels and agglutination titer (P less than 0.05) but non-significant when the specific anti-A IgG levels of individual serum samples were compared to their total IgG content (P greater than 0.05). Dose-response signals were similar for anti-A and anti-B IgM antibodies. Reproducibility of the assay was excellent. Specificity was ascertained by various approaches involving development of primary antibodies with heterospecific antibody conjugate and adsorption of primary antibody from serum using A and B group erythrocytes or soluble A and B substances. Separation of IgM from IgG anti-A antibodies over sizing gel resulted in fractions that were immunosorbed by mouse monoclonal anti-human IgM and IgG respectively but not vice versa. PMID- 2926152 TI - Characterisation of antibodies to urinary gonadotrophin peptide. AB - There is now general recognition that human chorionic gonadotropin (hCG), its beta subunit and its fragments are valuable diagnostic markers of trophoblastic and some non-trophoblastic malignancies. Urinary gonadotropin peptide (UGP) contains at least one epitope which cross-reacts with the beta-subunit of hCG. In order to assess the potential of UGP as a tumour marker in its own right, it was paramount that any measurements made could be regarded as specific for UGP and not cross-reactive with either hCG or human luteinising hormone (hLH). Four antibodies were tested, two polyclonal (AK12 and DR-Pool) and two monoclonal (2C2 and 6D3). Initial screening using radioiodinated (125I) UGP, hCG, hCG beta subunit and hLH showed that the polyclonal antibodies bound to all four gonadotrophins, whilst the monoclonal antibodies bound only to the radioiodinated UGP. The antibodies were tested in both radioimmunoassay (RIA) and immunoradiometric assay (IRMA-sandwich assay) systems. The parameters measured were sensitivity and specificity for UGP. The polyclonal antibodies used in the RIA system produced a sensitive assay (0.2 ng/ml UGP) which was relatively specific; cross-reactions for the AK12 antibody (at 50% inhibition) were 5% for hCG, 11% for its beta-subunit, 0.4% for the alpha-subunit and 2.6% for hLH. The monoclonal antibodies performed optimally in the IRMA system. Immobilised 2C2 and radiolabelled (125I) AK12 produced a system that had a sensitivity of 0.4 ng/ml UGP and cross-reactivity (50% maximum binding) of 2% for the hCG beta-subunit and less than 1% for hCG, hLH and the hCG alpha-subunit. PMID- 2926153 TI - The maximum conjugate frequency (alpha max) characterizes killer cell populations. AB - A quantitative procedure to characterize NK cell populations based on the dependence of the frequency of conjugation (alpha) on the effector-to-target ratio (R) is shown. To this end, a detailed study of the influence exerted by: (a) the value of R; (b) the number of effector and target cells (N, T); and (c) the source (donor) and enrichment of the effector cell population on the frequency of conjugation between NK effector and K562 target cells has been performed. This has demonstrated that for a given value of R large differences in the values of alpha can be obtained for different donors and/or N values. Hence, the usual practice of reporting the frequency of conjugation at a given value of R cannot be used as a valid criterion for comparison, and this could explain the differences in the alpha values reported in the literature for the same effector target system. Moreover, the frequency of conjugation depends on the enrichment of the effector cell populations, although it has been shown that in all cases a plot of 1/alpha vs. R for N = constant is always linear with intercept 1/alpha max.alpha max represents the maximum frequency of conjugation for an effector target system and remains constant for all values of R and N, and is also independent on the donor of the cell source. These characteristics make that the values of alpha max can be used as an easy criterion to determine with accuracy conjugate frequencies in an effector-target system, and could also be applied to characterize the activation or inhibition of effector cell populations by monoclonal antibodies or other agents. This criterion was applied to characterize the enrichment of NK cell populations and so, a value of alpha max = 58 +/- 3% has been obtained when highly purified (greater than or equal to 99%) NK effector cells obtained by panning with the monoclonal antibodies Leu-2, Leu-3 and Leu-4 are used. However, the corresponding value for MDC (14% NK cells) was lowered to 26 +/- 1%. PMID- 2926154 TI - Use of sparse-pore polycarbonate (Nuclepore) membrane for the measurement of chemotaxis of polymorphonuclear leukocytes. Comparison of 'micro-Boyden' chambers and estimation of 'drop-off' of cells. AB - Various modified Boyden chambers having upper and lower compartments of small volume ('micro-Boyden' chambers) were tested for their suitability for use with the recently described 'sparse-pore' polycarbonate (Nuclepore) membrane for the measurement of chemotaxis of polymorphonuclear leukocytes in vitro towards N formyl-methionyl-leucyl-phenylalanine. Previously reported 'open-well' and 'blind well' chambers, as well as a new chamber having a lower compartment made from perspex and an upper compartment made from silicone rubber were tested. The most satisfactory results were provided by the new chamber, and this is attributed to the easy, accurate filling of the lower compartment, the lack of distortion of membrane, and the reliability of the seals around the edges of the membrane which can be achieved with this chamber. Full humidification during assembly was necessary for obtaining maximal response of the cells through the 'sparse-pore' membrane in all types of micro-Boyden chamber. 'Drop-off' of polymorphonuclear leukocytes from the lower surface of the 'sparse-pore' membrane during incubation was also studied in these experiments and found to be slight. PMID- 2926155 TI - A two-site monoclonal antibody ELISA for the quantification of the major Dermatophagoides spp. allergens, Der p I and Der f I. AB - A two-site monoclonal antibody (Mab) ELISA was developed to measure the Group I allergens from Dermatophagoides spp., Der p I from D. pteronyssinus and Der f I from D. farinae. Species-specific Mabs were used to coat microtiter plates which were then incubated with allergen or house dust extracts. Bound allergen was detected using a biotinylated Mab which recognized a common epitope on both Der p I and Der f I, followed by the addition of streptavidin-peroxidase and ABTS/H2O2 substrate. The assay had low non-specific binding (approximately 0.08 absorbance units) and had a sensitivity of 5 ng/nl for aqueous allergen extracts (equivalent to 0.1 microgram allergen/g dust). 53 dust samples were assayed using the Mab ELISA and an RIA previously described using 125I-labelled Mab. The results showed a very good quantitative correlation between the assays (r = 0.96, p less than 0.001 for Der p I; r = 0.92, P less than 0.001 for Der f I). A further 132 dust samples from a different geographical areas were also assayed by both methods and gave correlation coefficients of 0.90 (P less than 0.001) and 0.86 (P less than 0.001) for Der p I and Der f I, respectively. The Mab ELISA will be useful in epidemiological studies of allergic asthma, both in the assessment of levels of dust mite allergen present in houses and the efficacy of allergen avoidance regimes. PMID- 2926156 TI - Analysis of complement factor B activation by PAGE-immunoblotting. AB - Initiation of complement activation via the alternative pathway results in cleavage of Factor B into two fragments Ba and Bb. Employing PAGE and immunoblotting analysis we have demonstrated Ba and Bb activation fragments following in vitro and in vivo activation in a range of biological fluids including cerebrospinal fluid and synovial fluid. Quantitative linearity was obtained over the range 5-20 micrograms/ml of Factor B and its fragments in body fluids. Using Davis-PAGE a previously unrecognised triple component heterogeneity of the Ba fragment was observed. This study demonstrates that immunoblotting may be used as a sensitive and quantitative tool for the detection and characterisation of the individual cleavage products of Factor B in complex biological fluids without prior purification. PMID- 2926157 TI - Antibody-coated target cell membrane-induced chemiluminescence by human polymorphonuclear leukocytes. AB - Activation of the oxidative metabolic burst of human polymorphonuclear leukocytes (PMN) by antibody-coated crude membrane fragments of K562 tumor cells was measured in a luminometer. Induction of the chemiluminescence (Cl) response was measured in the presence of luminol and lucigenin. The Cl was dependent on the concentration of PMN, the enhancer luminol or lucigenin, and the amount of tumor cell fragments and anti-K562 serum. PMN were not triggered to a Cl response in the absence of antibodies. The lucigenin-enhanced Cl involved superoxide anion detection while the luminol-enhanced Cl was dependent on the presence of myeloperoxidase and involved hydroxyl radicals. An intact cytoskeleton and energy were necessary for an optimal Cl response. PMID- 2926158 TI - Ewing sarcoma growth factor as a supplement for the cloning of hybridomas. PMID- 2926159 TI - Acute suppurative parotitis caused by Pseudomonas pseudomallei in children. AB - During a prospective clinical study of melioidosis in northeast Thailand, suppurative parotitis was observed as a characteristic presentation in children. Parotitis constituted 6.3% of all culture-positive melioidosis and 38% of melioidosis in children. Nine cases are described. None had apparent predisposition to infection, although two patients developed rising mumps virus antibody titers, suggesting a possible relation between these conditions. Complications included abscess formation (nine), spontaneous rupture into the auditory canal (five), facial nerve palsy (two), and septicemia and osteomyelitis with septic arthritis (one each). All children initially responded to surgical drainage and appropriate antibiotic therapy. Pseudomonas pseudomallei parotitis should be considered in children from endemic areas with fever and facial swelling. It has a good prognosis with appropriate treatment. It may also prove to be a sensitive clinical indicator of the presence of melioidosis within a particular geographic area. PMID- 2926160 TI - Association of recurrent chlamydial infection with gonorrhea. AB - To determine whether concurrent gonorrhea reactivates latent chlamydial infection, we studied 74 recurrent chlamydial infections and the effect of concurrent gonorrhea at the recurrent episode on the chlamydial serovar identified. Serotyping of 74 recurrent pairs of chlamydial isolates from patients attending a sexually transmitted diseases clinic indicated that 47.1% (16 of 34) with gonorrhea at the time of recurrence harbored chlamydiae of the same serovar as at the initial infection, while only 22.5% (9 of 40) without gonorrhea had the same serovar (P = .03). The proportion of recurrences by the same serovar in the group without gonorrhea did not differ from the proportion predicted by a random exposure model (22.2% vs. 18.4%, P = .46), while the proportion in the gonorrhea group did (47.1% vs. 19.8%, P less than .0001). The possibility of reinfection did not appear more likely in the group with gonorrhea than in the group without. These observations support the hypothesis that concurrent gonorrhea can reactivate latent chlamydial infection. PMID- 2926161 TI - Diversity and sources of rapidly growing mycobacteria associated with infections following cardiac surgery. AB - Eighty-nine isolates of rapidly growing mycobacteria associated with cardiac bypass-related infections were characterized. Isolates from sporadic infections belonged to eight taxonomic groups and displayed numerous multilocus enzyme genotypes, plasmid profiles, and heavy metal and antibiotic resistance patterns. Compared with 449 noncardiac wound isolates, 45 sporadic cardiac isolates were more likely to be Mycobacterium fortuitum and M. smegmatis and less likely to be M. chelonae. About 80% of cardiac and noncardiac isolates were from southern coastal states. Eight outbreaks of cardiac bypass-related infections were identified. Strains from each outbreak were genotypically distinctive, and five outbreaks involved more than one strain. In two outbreaks, isolates from environmental sources and noncardiac infections were similar or identical to isolates from sternal wound infections. The heterogeneity of these isolates suggests that most isolates are unrelated and are derived from local environmental sources rather than from contaminated commercial surgical materials or devices. PMID- 2926162 TI - Treatment of experimental invasive aspergillosis with novel amphotericin B/cholesterol-sulfate complexes. AB - An immunosuppressed rabbit model of invasive aspergillosis was used to evaluate a novel micellar preparation of cholesterol sulfate complexed to amphotericin B. The acute LD50 of amphotericin B-deoxycholate was 5.1 mg/kg versus 20 mg/kg for the amphotericin/cholesterol-sulfate complexes. Amphotericin B-deoxycholate given iv at a dose of 1.5 mg/kg was more effective in sterilizing liver and kidney than the amphotericin/cholesterol-sulfate complexes given iv at 1.5-4.5 mg/kg, but infection persisted in the lungs of all rabbits treated with those doses. Infection persisted even when the rabbits were given a lethal dose of amphotericin B-deoxycholate (4.5 mg/kg), but a dose of 15 mg/kg of the amphotericin/cholesterol-sulfate complexes sterilized tissues and was associated with no acute lethality. Equivalent doses of the amphotericin/cholesterol-sulfate complexes were less effective than amphotericin B-deoxycholate, but a fourfold decrease in acute lethality improved the therapeutic index of amphotericin B. The amphotericin/cholesterol-sulfate complexes appear to be an improved means of amphotericin B delivery and may improve therapy for invasive aspergillosis. PMID- 2926163 TI - Recent primary toxoplasma infection indicated by a low avidity of specific IgG. AB - An unusual assay was developed for the serologic diagnosis of recent primary infection by Toxoplasma gondii. This test measures the antigen-binding avidity of toxoplasma-specific IgG antibodies. Serum samples from 5 patients with recent primary toxoplasma infection were compared with those from 21 subjects with preexisting toxoplasma immunity. Patients with primary infection exhibited a low avidity of toxoplasma-specific IgG, which persisted for several months after the onset of symptoms of toxoplasmosis. In contrast, all subjects with past immunity had a high avidity of toxoplasma-IgG. This IgG avidity assay should assist in the diagnosis of acquired toxoplasmosis and may be used to identify pregnancies that are at risk for congenital toxoplasmosis. PMID- 2926164 TI - Azidothymidine steady-state pharmacokinetics in patients with AIDS and AIDS related complex. PMID- 2926165 TI - Oral ribavirin therapy for subacute sclerosing panencephalitis. PMID- 2926166 TI - Exanthem subitum and antibody to human herpesvirus-6. PMID- 2926167 TI - Demonstration of a barrier to transplacental passage of murine enteroviruses in late gestation. PMID- 2926168 TI - Plasma endotoxin: increased levels in neutropenic patients do not correlate with fever. PMID- 2926169 TI - Effect of combined therapy with ansamycin, clofazimine, ethambutol, and isoniazid for Mycobacterium avium infection in patients with AIDS. PMID- 2926170 TI - Tumor necrosis factor in leprosy patients. PMID- 2926171 TI - Differences in virulence and development of encephalitis during chronic infection vary with the strain of Toxoplasma gondii. PMID- 2926172 TI - Immunotherapy for gram-negative septic shock. PMID- 2926173 TI - High-dose dexamethasone in malaria. PMID- 2926175 TI - Borrelia burgdorferi attachment to mammalian cells. PMID- 2926174 TI - Tick-borne relapsing fever in intravenous drug abusers. PMID- 2926176 TI - Multiple organ involvement by Legionella pneumophila in a fatal case of Legionnaires' disease. PMID- 2926177 TI - Nontoxigenic Vibrio cholerae wound infection after exposure to contaminated lake water. PMID- 2926178 TI - Vertebral osteomyelitis due to Haemophilus aphrophilus: treatment with ceftriaxone. PMID- 2926179 TI - The pancreas and oxygen consumption. 1. Pancreatic oxygen consumption in normo- and hypovolemic dogs. AB - Pancreatic oxygen consumption (VO2) was studied in hypovolemic shock: 4 dogs served as controls and 4 others were kept at 50 mm Hg of mean arterial blood pressure. All 8 were studied for a period of 3 h. Pancreatic VO2 was obtained by adding up VO2 for the head (minus the uncinate process) and tail of the pancreas both equal to the product of regional blood flow times O2 extraction. Regional blood flows were measured electromagnetically on the gastroduodenal (GDA) and the splenic (SA) arteries, whereas O2 extraction was derived from total hemoglobin (THb) and oxygen saturation of hemoglobin (%O2 Hb) determined on the right femoral artery (RFA), the superior pancreaticoduodenal (SPDV), and splenic (SV) veins. A splenectomy was performed in all 8 dogs. Controls showed a significantly elevated pancreatic VO2 from the first hour of observation on (+56% after 1 h, +92% after 3), whereas pancreatic VO2 remained strictly unchanged throughout shock (+2% and +6%, at one and 3 h, respectively), despite significant increases in O2 extraction. These findings give support to the deleterious effects of hypovolemia to the pancreas and that pancreatic O2 extraction indicates metabolic damage to be less severe than observed in experimental bile-trypsin-induced acute pancreatitis. PMID- 2926181 TI - Whole body hyperthermia in dogs using a radiant heating device: effect of surface cooling on temperature uniformity. AB - Rectal and subcutaneous temperatures were measured during a total of 10 whole body hyperthermia treatments conducted in six dogs. During five of the treatments skin cooling, by means of initiating air flow through the radiant heating device, was necessary during the plateau phase because rectal temperature exceeded the target value. Skin cooling was not necessary in the other five treatments. Although the rectal temperatures were similar in all 10 treatments, extensive and rapid subcutaneous temperature non-uniformity, of approximately 4 degrees C, developed during treatments where skin cooling was necessary. During the treatments where skin cooling was not necessary, the subcutaneous temperature remained approximately equal to the rectal temperature. These data indicate that the environment in the radiant heating device during the plateau phase can have a profound effect on the temperature at superficial sites, which is not reflected by the temperature measured at deeper sites. The temperature at superficial sites should be measured during whole body hyperthermia to assure that the prescribed heat dose is administered to the largest percentage of body mass possible. Active skin cooling during whole body hyperthermia should be avoided if possible. PMID- 2926182 TI - Heat-induced damage to HeLa-S3 cells: correlation of viability, permeability, osmosensitivity, phase-contrast light-, scanning electron- and transmission electron-microscopical findings. AB - The responses of HeLa S-3 to mild hyperthermia for relatively critical times at 43 and 45 degrees C were analysed in detail, including growth and colony-forming ability, permeability, osmotic sensitivity and microscopical appearances. For comparative purposes lower temperatures (e.g. 41 degrees C) and higher temperatures (50 and 55 degrees C) were used in some experiments. The evidence from many different aspects, including scanning and transmission electron microscopy, suggests that critical heat exposures do not per se cause severe membrane damage and loss of cell integrity, but changes quickly become manifest when cells are 'recovered' by returning to 37 degrees C. Attention is drawn to the ability of heat-treated cells to show osmotic-like swelling and restoration towards normal volume in medium of 30 per cent normal strength, which would not be expected on the hypothesis that hyperthermia primarily disrupts membrane structure and functioning. Ultrastructural changes during and after hyperthermia- including nucleolar changes, the appearance of perichromatin granules, the formation of electron-dense cytoplasmic clusters, and the development of intranuclear actin rods--corroborate and extend other findings. However, mitochondrial changes were found to be particularly significant, appearing early and correlating well with the loss of viability and metabolic functioning found after heat treatment. These include the early development of intramitochondrial dense granules, followed by vesicularization of the cristae, swelling of the intracristal spaces, myelin degeneration and the formation of bodies which could otherwise be mistaken for secondary lysosomes. The findings indicate the need for more intensive investigations of mitochondria and mitochondrial functioning in hyperthermia-induced cell damage, and their careful correlation with the 'recovery' of energy-dependent process in cells subsequently returned to 37 degrees C. PMID- 2926180 TI - Hydralazine-induced enhancement of hyperthermic damage in a C3H mammary carcinoma in vivo. AB - Prolonged oxygen deprivation of cells in vitro or in vivo increases the sensitivity of those cells to heat. Hydralazine is a peripheral vasodilator, currently used clinically as an antihypertensive agent, which has been reported to be able to reduce tumour blood flow and increase the degree of tumour hypoxia. We have investigated the potential of hydralazine to enhance the response of a C3H mammary carcinoma to local hyperthermia. The tumour was grown in the foot of mice and its response to treatment assayed by regrowth delay. Our results show that a single intravenous injection of hydralazine (5 mg/kg) significantly enhances the heat damage produced by heating for various times at either 41.5, 42.5, or 43.5 degrees C. This effect was dependent on the time of starting to heat after hydralazine injection, with the greatest enhancement occurring when heat was given within 1 h following drug administration. However, the effect was independent of the hydralazine concentration, at doses above 2.5 mg/kg. Hydralazine also significantly decreased mean arterial blood pressure and the uptake of 86RbCl into tumours. Our results suggest that the observed heat sensitization was primarily a consequence of an increase in tumour hypoxia, probably resulting from a decrease in tumour blood perfusion. PMID- 2926183 TI - Effect of hyperthermia on intracellular drug accumulation and chemosensitivity in drug-sensitive and drug-resistant P388 leukaemia cell lines. AB - Enhancements of the drug-induced cytotoxicity and modifications of drug transmembrane equilibria caused by hyperthermic treatment were analysed on P388/S and P388/R murine leukaemia cell lines. The P388/R cell line was derived from the P388/S cell line by drug selection of mutant, drug-resistant clones; it expresses a pleiotropic drug resistance towards some chemotherapeutic drugs such as doxorubicin, daunorubicin and etoposide, but is only weakly resistant towards other drugs as cis-diammine-dichloroplatinum. Hyperthermic treatment enhanced the drug cytotoxic effects much more on the P388/R cell line than on the P388/S line, but the cytotoxic enhancements were consistent only for the drug towards which the P388/R cell line expresses pleiotropic resistance. Intracellular drug accumulation analysis and drug transmembrane equilibria determinations indicated that the resistance of both cell lines to the intracellular drug was not affected by hyperthermic treatment, whereas variations in drug influx, but not in drug extrusion, were induced by heat treatment. The study suggested, therefore, that hyperthermia does not modify intracellular chemosensitivity of either cell line, but acts on membrane permeability by facilitating attainment of the intracellular drug concentrations needed to cause the cytotoxic effect. PMID- 2926184 TI - Co-isolation of heat stress and cytoskeletal proteins with plasma membrane proteins. AB - Previous reports have suggested the possible existence of a plasma-cell-membrane function associated with some heat stress proteins (HSPs). To investigate the effect of hyperthermia on plasma membrane proteins, rat mammary tumour clone C (MTC) cells were heated at 42 degrees C for 1 h. Their surface proteins were (1) labelled with [3H]leucine, (2) biotinylated, (3) affinity isolated with streptavidin-agarose beads under denaturing or non-denaturing conditions, and (4) analysed by one- and two-dimensional polyacrylamide-gel electrophoresis and protein blotting under denaturing conditions. Affinity isolation of biotinylated proteins enriched for a protein subfraction believed to be membrane-associated. Several proteins analogous to HSP or their heat-stress cognates (HSC) were present with these biotinylated protein subfractions in control or heated cells. The major and most consistent feature of affinity isolates from heated cells was the presence of a small fraction of the induced 68-kD HSP. The 112-, 90-, 70- and 22-kD HSC/HSP were also present in small amounts in affinity isolates of control cells, and the fraction increased in heated cells. Several structural proteins, including actin and the tubulins were present in the same affinity isolates. Protein blotting experiments indicated that none were exposed on the exterior of the plasma-cell membrane or biotinylated and thus none were exposed on the exterior of the plasma-cell membrane or biotinylated intracellularly through membrane damage. These results suggest that small fractions of several HSC are located at or near the cytoplasmic face of the plasma membrane along with cytoskeletal proteins, and that additional submembranous localization of HSP occurs after heat stress and may be part of the processes associated with membrane damage or cellular responses to heat. Further studies will be directed at establishing the relationships between these proteins and the role, if any, of the changes associated with heat stress. PMID- 2926186 TI - A computational model for heat generation in a radially layered tissue inside a 'coaxial TEM' applicator. AB - The electromagnetic heat dissipation in a radially layered biological tissue inside a circular cylinder has been investigated theoretically. The theory is based on a three-dimensional model and the electromagnetic field is assumed to be generated by a prescribed electric field along a ring-shaped aperture. The method of computation employs the spatial Fourier transform of all field quantities with respect to the axial coordinate, after which the field equations are solved in the spectral domain. Subsequently, an inverse Fourier transform is carried out to compute the quantities that are of interest to the clinical deep-body hyperthermia system at hand. For a number of representative configurations numerical results at 70 MHz are given. PMID- 2926185 TI - The effect of angiotensin II on blood flow in tumours during localized hyperthermia. AB - The selective enhancement of drug delivery to tumours is an important factor in the effectiveness of thermochemotherapy as well as in standard normothermal chemotherapy. We have attempted to clarify experimentally using AH 100B tumour bearing rats whether or not a selective increase in blood flow in tumours can be produced under specific conditions of local hyperthermia by administration of angiotensin (AGT II). AGT II (2 micrograms/kg/min) produced an elevation of blood pressure (ca. 150 mm Hg) when local hyperthermia, at 41, 43, and 45 degrees C, was induced. Furthermore, at 41 and 43 degrees C a selective increase in blood flow in tumours resulted from the AGT II-induced hypertension. By contrast, a decrease in blood flow was observed at 45 degrees C both in tumour and in muscle. These results indicate that AGT II-induced hypertension and the resultant selective increase in drug delivery to tumours during the initial phase of heating may result in an augmentation of the anticancer effects of thermochemotherapy. PMID- 2926187 TI - Heat loss and blood flow during hyperthermia in normal canine brain. I: Empirical study and analysis. AB - The effects of blood flow and thermal conduction during microwave hyperthermia were investigated in normal canine brain. Heating was accomplished with an external microstrip spiral antenna and temperature measurements were made using a multichannel fluoroptic thermometry system. In order to determine cooling rates, temperature measurements made during cooling were fitted with a model consisting of a constant value and an exponential term. Data from experiments in both perfused and non-perfused brains could be fitted with this simple model. The resulting cooling rates indicated that heat loss by conduction is comparable to that by blood flow. In another series of experiments, temperature measurements were made during several 1 min cooling intervals in which the power was shut off intermittently during a 35 min heating episode. Results were consistent with a 2 3-fold increase in blood flow rate which occurred gradually throughout the course of heating. Parameters that affect the determination of cooling rates are discussed in terms of the bioheat transfer equation. These investigations demonstrate that a simple heat sink model provides a good representation of the cooling data for the thermal distributions obtained. PMID- 2926188 TI - Heat loss and blood flow during hyperthermia in normal canine brain. II: Mathematical model. AB - A mathematical model for heating and cooling during hyperthermia has been developed from an appropriate solution of a bioheat transfer equation. Predicted cooling rates obtained from the model have been compared with cooling rates obtained from experiments performed on both perfused and non-perfused normal canine brain tissue. The agreement between the predicted and observed cooling rates in non-perfused tissue is satisfactory (within 6-11 per cent) and provides confidence that the conduction process is being accurately represented. The model is then used to estimate the relative contribution of conductive and convective (blood flow) heat loss during cooling for the in vivo experiments. Estimates of blood flow dynamics are made from cooling data taken early and late in a heating course using the model to correct for conductive heat loss. Simplified forms of the bioheat transfer equation are examined. An adequate model for the observed cooling data is one that treats heat loss (both conduction and blood flow) as a heat sink (i.e. an effective perfusion model) rather than an effective thermal conductivity model. PMID- 2926189 TI - An interstitial hyperthermia system at 27 MHz. AB - An interstitial hyperthermia system using thin, flexible wires operating at a frequency of 27 MHz has been evaluated for possible use in combination with (iridium) brachytherapy applications employing flexible nylon afterloading catheters. This method of interstitial heating is argued to be a variation of local-current-field heating, however with the direct galvanic contact between electrode and tissue replaced by a capacitive coupling between wire and tissue. Through a special design of the wire the length of the heated area along the catheter can be chosen freely. Standard non-prepared implantation catheters can be used, so that no change from the established implantation techniques is required. Possible advantages of these 27 MHz wires over coaxial dipole antennas at higher frequencies are simplicity and low cost of the heating system, free choice of effective heating length for each wire and uniformity of heating along this effective heating length up to the tip of the wire. Flexibility of the wires is maintained, enabling application in curved (even U-shaped) catheters, e.g. for head and neck implantations. Impedance matching of the wires to the generator, necessary for an optimal transfer of power, appears possible by means of a variable air coil. Care should be taken to avoid stray capacitances of the connecting cables with respect to ground or among the different cables used. Measurements in muscle-equivalent split phantoms with infrared thermography have been performed with both single and multiple wires. The resulting SAR distributions confirm the working principle of these low-frequency wires (resistive heating) and illustrate the difference with radiative antennas at higher frequencies. The system is being applied both in experimental animal studies and in a clinical pilot study. PMID- 2926190 TI - 'Thermal dose': comments on papers presented at the NAHG workshop. PMID- 2926191 TI - [Nipple stimulation contraction stress test and oxytocin challenge test in evaluating fetal well being in high risk pregnancy]. PMID- 2926192 TI - [Relationship between social factors and urinary catecholamine concentrations in pregnant women]. AB - Catecholamine concentrations were measured in urine obtained from pregnant women to estimate the stress resulting from their lifestyles. Adrenaline and noradrenaline were analysed by high performance liquor chromatography (HPLC), creatinine was measured by Jaffe's method, and the catecholamine-creatinine ratio in urine was calculated. Adrenaline concentrations in 24-hour urine were higher in working women (n = 35) than non-working women (n = 20) (p less than 0.001) and the admission group (n = 20) (p less than 0.05), but noradrenaline concentrations showed no significant difference among three groups. Catecholamine concentrations were measured in 89 pregnant women three times in 24 hours. Marked circadian variations were observed with adrenaline and noradrenaline. Both concentrations were lowest in early morning, and increased after work (or evening) (p less than 2.0 X 10(-8)). Adrenaline concentrations were decreased on retiring to bed (p not equal to 1.0 X 10(-5)), while noradrenaline concentrations remained high until retiring to bed. There seems to be a relationship between catecholamine output and working or the familial factor. In working women (n = 53), noradrenaline concentrations were higher than in non-working women (n = 36) in early morning (p less than 0.05) and on retiring to bed (p less than 0.05). On the other hand, in women living with parents (n = 56), adrenaline concentrations were higher than those in women living without parents (n = 33) in early morning (p less than 0.05) and on retiring to bed (p less than 0.05). From these results, it may be concluded that working women or women living with parents are under much stress in their lives. PMID- 2926193 TI - [Relationship between coagulation-fibrinolysis kinetics and the severity and predictability of toxemia of pregnancy]. AB - Various attempts have been made in recent years to identify the cause and pathophysiology of toxemia of pregnancy from the standpoint of changes in blood coagulation and fibrinolysis. It is believed that in toxemia of pregnancy, the fibrinolytic process changes as coagulation is augmented. However, definite conclusions about this sequence of events have not yet been reached. This study was designed to analyze the severity of toxemia of pregnancy and to examine the possibility of anticipating its onset from the standpoint of coagulation fibrinolysis kinetics. The patient population comprised 116 women divided into 4 groups: I) A control group of 10 normal, nonpregnant women; II) Fifty-four normal pregnant women who were followed up from early pregnancy until delivery; III) Twenty-four women who were followed up from early pregnancy until delivery and developed toxemia of pregnancy; and IV) Twenty-eight women with severe toxemia of pregnancy of the pure type who were referred to our institution at the onset of the disease and were treated as inpatients. Intergroup comparison yielded the following results. 1. In group II (normal pregnancy), a significant increase was observed, first in fibrinopeptide B beta and then in fibrinopeptide A, as the pregnancy progressed. This suggested the acceleration of coagulation and fibrinolysis due to pregnancy. 2. In group III (6 of 24 cases developed severe toxemia of pregnancy), AT-III increased, while protein C and hematocrit levels increased relative to those on the normal pregnancy group during the 2nd trimester. Thus, changes in coagulation functions occurred before the onset of toxemia of pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2926194 TI - [New method for preventing spinal headache (prophylactic blood patch method)]. AB - After spinal anesthesia, early ambulation frequently caused spinal headache. If the patient was discharged on the day of the operation, spinal headache occurred very frequently. With epidural anesthesia, if the dura was erroneously punctured with the needle, headache often occurred. In order to prevent spinal headache, we tried the Blood Patch Method during operation (Prophylactic Blood Patch Method). Epidural catheterization and spinal tap were simultaneously performed. The epidural catheter was threaded 3 cm cephalad in the epidural space. Five ml Venous blood of the patient was injected through the epidural catheter (Blood Patch Method). Epidural puncture was performed one spinal segment cephalad (A Method) or one spinal segment cauded (B Method) from the site of spinal puncture. The prophylactic Blood Patch Method was very effective in preventing spinal headache after the dural puncture. Especially B Method, in which blood was injected near the dural pore, was much more effective than A Method. PMID- 2926195 TI - [Comparative studies on steroidogenesis and prostaglandins production by luteal cells in newly formed corpora lutea and early pregnancy]. AB - The present study was undertaken to assess the ability of cultured luteal cells from human corpora lutea (CL) in the mid luteal phase and the early pregnancy to secrete steroids and prostaglandins (PGs). Luteal cells responded to hCG with a significant increase (2- to 4-fold) in progesterone (P) production. The addition of hCG to the culture media did not stimulate estradiol (E2) production. In contrast, both P and E2 secretion by luteal cells in early pregnancy were significantly lower than those found in the mid luteal phase. Exposure to hCG did not affect P production by luteal cells in early pregnancy. Arachidonic acid (AA) significantly stimulated PGE2 synthesis by luteal cells in the mid luteal phase in a dose-dependent manner. Both basal PGE2 production and the responsiveness to AA were maintained for the duration of the culture. However, hCG did not affect AA-stimulated PGE2 production. Both PGF2 alpha and 6-keto-PGF1 alpha production abruptly declined as the culture proceeded. PG synthesis by cultured luteal cells in early pregnancy was significantly lower than in the mid luteal phase. The ultrastructural characteristics of luteal cells in early pregnancy, which contained lipid droplets, granular and agranular endoplasmic reticulum and large spherical mitochondria, were maintained after 10 days in culture. The present results demonstrate that P and PGE2 production by cultured luteal cells predominate during the mid luteal phase. These data suggest that PGE2, but not PGF2 alpha, may be involved in the regulation of CL function in the menstrual cycle. PMID- 2926196 TI - Prediction of clinical course and recurrence of human ovarian cancer by several serum tumor markers. AB - Measurement of serum tumor markers [lactate dehydrogenase (LDH), alpha hydroxybutyrate dehydrogenase (HBD), LDH-4, erythrocyte sedimentation rate (ESR), carcinoembryonic antigen (CEA), beta 2-microglobulin (beta 2M) and CA 125] was done before and after operation, and during the course of chemotherapy in 43 patients with advanced primary ovarian cancer. Pre-operative positive results for these serum tumor markers were 94.4% for CA 125, 62.2% for beta 2M, 54.8% for HBD, 51.3% for ESR and 46.5% for LDH, respectively. In a group of patients from whom most of the tumor mass had been removed, LDH, LDH-4 and HBD significantly declined after the operation, whereas in a group of patients with a large residual tumor after operation no significant change in any of the serum tumor markers examined was observed after operation. Except for CEA, all serum tumor markers in patients with complete response to chemotherapy significantly decreased after 3 courses of chemotherapy. From the analysis of predictive values for the recurrence of ovarian cancer, the most reliable tumor markers as a single marker appeared to be CA 125 and CEA, followed by ESR, LDH and LDH-4. However, in about 10% of cases, abnormal levels of CA 125 or CEA before treatment returned to the normal range after treatment and an increase in the other tumor markers was observed with a relapse of disease in the absence of an increase in CA 125 or CEA. These results suggest that in addition to such tumor markers as CA 125 or CEA, a combination assay of several tumor markers is necessary for monitoring of treatment of ovarian cancer. PMID- 2926198 TI - [Fetal monitoring with a combination transducer for FHR and uterine contraction- production of the transducer]. PMID- 2926197 TI - Direct inhibitory ovarian effects of prolactin in the process of ovulation. AB - The present study was designed to determine the effects of prolactin (PRL) on the process of follicle rupture and oocyte maturation using an in vitro perfused rabbit ovary model. In the first experiment ovaries were perfused for 12 hours with or without PRL at 10(2) or 10(3) ng/ml. Ovulation did not occur in any ovaries in the absence of gonadotropin. The majority of follicular oocytes did not progress beyond the germinal vesicle stage following treatment with PRL. The percentage of follicular oocytes which showed evidence of degeneration was also comparable in both groups. The concentrations of progesterone in the perfusate did not differ significantly between PRL-treated and control ovaries. In the second experiment, ovaries were perfused with or without PRL at 10, 10(2), or 10(3) ng/ml. Thirty minutes later 50 IU of human chorionic gonadotropin (hCG) was added to the perfusate of all ovaries. The addition of PRL to the perfusate inhibited hCG-induced ovulation in a dose-related fashion. The degree of ovum maturity and degeneration was comparable in the two groups. PRL did not affect hCG-stimulated progesterone production by the perfused rabbit ovaries. The present study demonstrates that PRL acts directly on the ovary to influence the process of ovulation, resulting in the inhibition of hCG-induced follicle rupture. These data suggest that PRL inhibits ovulation by mechanism(s) independent of ovarian progesterone synthesis. PMID- 2926199 TI - [The analysis of bioenergetics of mouse uterine muscle by magnetic resonance spectroscopy (MRS)]. PMID- 2926200 TI - [The platelet aggregation inhibition activity of placental brush border membrane]. PMID- 2926201 TI - [Prenatal diagnosis of a fetal cardiac tumor]. PMID- 2926202 TI - Autogenous vein and nerve grafts: a comparative study of nerve regeneration in the rat. AB - A new experimental model using the rat sciatic nerve has been devised and used in ten rats to compare the results of using a vein and a nerve graft in different fascicles of the same sciatic nerve, a third fascicle being preserved intact as a control. The results, judged clinically, electrophysiologically and histologically, show persistence of the vein graft as a conduit even six months after the operation and a similar pattern of nerve regeneration in the two different grafts. PMID- 2926203 TI - Multiple carpo-metacarpal dislocations. AB - Ten patients with closed multiple carpo-metacarpal dislocations have been reviewed. Closed manipulation was found to be successful if performed within two days of the injury. Plaster cast immobilisation supplemented by percutaneous Kirschner wire fixation is recommended to maintain the reduction, due to the unstable nature of the dislocation. Early appropriate treatment of these injuries carries a good prognosis. PMID- 2926204 TI - Treatment of solitary enchondromas in fingers. AB - The results after operative treatment of 21 solitary enchondromas of finger bones are described. 15 cases were treated by curettage and cancellous bone grafting, five by curettage alone, and one with amputation. One case did not heal after curettage and grafting. When symptoms are present or the cortical strength is decreased, we recommend operation. We find that the eccentric type of enchondroma can be treated adequately by curettage alone, while curettage and filling of the cavity with cancellous bone should be preferred in the central and polycentric forms. It is important that all material is removed from the cyst, which has to be packed completely with bone chips. The possibility of malignant change in enchondromas should be borne in mind, but we did not see this. PMID- 2926205 TI - Bilateral torsion of the radius: a case report. AB - A case of bilateral non-traumatic torsion of the radius affecting forearm rotation is described. PMID- 2926206 TI - Nerve abscess simulated by a lipoma in a leprosy patient. AB - A case of suspected giant nerve abscess near the radial nerve in the upper arm of a patient with borderline leprosy is reported. On exploration, it turned out to be a deep seated lipoma. Consideration should be given to exploring nerve masses in leprosy. PMID- 2926207 TI - Flexor tendon sheath haematoma: a case report. AB - An open finger injury reported here was diagnosed as a division of the flexor tendons of the little finger. However, surgical exploration revealed intact tendons encased in a tense flexor tendon sheath haematoma. Decompression of the haematoma led to a satisfactory recovery of finger function. PMID- 2926208 TI - A tale of two hands. PMID- 2926209 TI - A rapid method of removal of rings impacted in fingers. PMID- 2926210 TI - A technique for removal of a tight ring. PMID- 2926211 TI - The "cage" splint: an added protection for flexor tendon repair. PMID- 2926212 TI - A technique for distal digital replantation. PMID- 2926213 TI - A comparison of results of extensor tendon repair followed by early controlled mobilisation versus static immobilisation. AB - To compare the functional results of early controlled mobilisation and static immobilisation following repair of extensor tendons, we conducted a comparative study between two centres. In one, a consecutive series of tenorrhaphy patients was treated post-operatively by the dynamic splinting technique. In the other, a consecutive group was treated by static splinting. All patients treated by dynamic splinting were graded excellent within six weeks following surgery; no tendon ruptures occurred and no secondary corrective tendon surgery was required. After static splinting, 40% were graded excellent, 31% good, 29% fair, and none poor; six fingers treated by static splintage subsequently required tenolysis. Following surgical repair of extensor tendons of the hand, patients treated by early controlled motion regain better flexion function in terms of grip strength and pulp-to-palm distance. Dynamic splinting is a more effective technique than static splinting in the prevention of extensor lag. PMID- 2926214 TI - Dynamic traction after extensor tendon repair in zones 6, 7, and 8: a retrospective study. AB - Review of the notes of 46 extensor tendon repairs in 21 patients treated by post operative dynamic traction without an M.P. flexion block, no tendon ruptures or extensor lag and only one digit without full flexion after a mean follow-up of seven weeks. Re-examination of 26 treated repairs in nine patients for this study demonstrated a mean T.A.M. of 259 degrees at an average 14 months follow-up. No bow-stringing occurred because the extensor retinaculum was not excised, and no tenolyses were necessary. PMID- 2926216 TI - Experimental research in hand surgery. PMID- 2926217 TI - Dupuytren's disease in patients from the Indian sub-continent. Report of ten cases. AB - We report on ten patients from the Indian sub-continent operated on in our unit for Dupuytren's contracture. Their presentation, operative findings and subsequent course was indistinguishable from Caucasian patients. We believe that Dupuytren's disease among Indians is not so rare as previously thought. PMID- 2926215 TI - Deformation of the nail following elastic band traction--a case report. AB - Dynamic elastic band traction applied to the nail is commonly used in the post operative management of flexor tendon injuries and complications are few. We describe a self-resolving deformation of the nail resulting from its use. PMID- 2926218 TI - An accessory superficialis tendon involved by Dupuytren's contracture. AB - A 60-year-old Caucasian male presented with Dupuytren's contracture affecting his left little finger. On exploration he was found to have a band of Dupuytren's tissue attached to an accessory superficialis tendon. PMID- 2926219 TI - Centralisation of the radial club hand by gradual distraction. AB - Centralisation of the carpus on top of the distal end of the ulna in radial club hand of types III and IV has been performed by gradual distraction. For this purpose, I have used the apparatus originally developed for lengthening of digital structures and the forearm. This technique avoids extensive dissection and acute stretching of the radial neuro-vascular structures. Experience has shown that gradual distraction is a safe and relatively simple method for correction of the deformity, particularly in long-standing and neglected cases. PMID- 2926220 TI - Intra-arterial injection of dextropropoxyphene into hand arteries. AB - We report a case of deliberate intra-arterial injection of dextropropoxyphene into the palms, leading to chronic oedema of both hands. The aetiology is discussed. This cause must be borne in mind in the diagnosis of chronic oedema of the hands. PMID- 2926221 TI - Pain relief after free flap reconstruction in adriamycin necrosis on the dorsum of the hand. A case report. AB - A free flap transfer in a case of Adriamycin necrosis on the dorsum of the hand is reported. The advantages of this method of reconstruction are discussed. PMID- 2926222 TI - Chronic compartment syndrome of the flexor muscles in the forearm: a case report. AB - A case is reported of a professional racing motor-cyclist who developed a chronic compartment syndrome of the flexor muscles in the forearm, confirmed by pressure measurements after exercise. Open fasciotomy of both the superficial and deep compartments cured the condition. PMID- 2926223 TI - CT in established Volkmann's contracture in forearm muscles. AB - Differential diagnosis between true and pseudo-Volkmann's contracture should not be based on clinical grounds alone, because clinical data are often insufficient in determining the severity and the extent of muscle damage. CT has been utilised in 11 cases where a flexion contracture of the forearm muscles was present and corresponded closely with the surgical findings. True and pseudo-Volkmann's contracture can thus be distinguished and the severity and extent of the muscle damage determined. PMID- 2926224 TI - Three-dimensional CT imaging for wrist disorders. AB - Three-dimensional CT imaging of the wrist was performed in 20 patients: three with Kienbock's disease, 14 with fractures or dislocations of the carpal bones, two with dislocation of the distal radio-ulnar joint and one with an intra articular fracture of distal radius. These images were compared with those of plain radiographs and computed tomography. With the exception of two cases of distal radio-ulnar joint dislocation and one case of hamate body fracture, three dimensional CT imaging was helpful in detecting the displacement of the fracture and in determining the location and the direction of the displaced carpal bone. Furthermore, the presence of small fragments could be observed more easily in the three-dimensional CT image. Three-dimensional CT imaging provides a great deal of information that cannot be obtained by conventional radiographs or CT images even at their present stage of technical development. PMID- 2926225 TI - Usefulness of myelography in brachial plexus injuries. AB - Ninety brachial plexus lesions have been examined by myelography and the results classified into six types. These were compared against the level of lesion found at exploration of the brachial plexus with electrophysiological investigations carried out during the operation. The results show that myelography can be a reliable and useful pre-exploratory measure to assess the level of the lesion of each injured root. PMID- 2926226 TI - The first web hand flap. AB - Cadaveric dissections demonstrated a constant blood supply to the skin of the first web. An island advancement flap from the dorsum of the first web was used to release first web contractures in six patients and to resurface palmar burns in two. There were no flap losses and its use is recommended in release of moderate contractures and minor loss of palmar skin. PMID- 2926227 TI - The use of the latissimus dorsi muscle as an active motor unit for digital flexion. AB - A technique is described to restore flexion of the fingers and thumb using a latissimus dorsi muscle island as an active motor unit. It has been performed in a ten-year-old child with a satisfactory result. PMID- 2926228 TI - Surgical treatment of the clasped thumb. AB - We report a series of 12 patients (19 hands) with clasped thumb who underwent surgical treatment. The series is divided into three groups. In the first group, the prominent pathological feature was hypoplasia of the extensor tendons which was treated by tendon transfer. The second group, the arthrogryphotic type, had contracture of the intrinsic muscles of the thumb and shortening of the skin; these needed mainly release operations. In only three hands out of nine was tendon transfer performed. The third group was defined by a combination of skeletal, muscular and tendon hypoplasia. Instability of the M.P. joint and adduction contracture of the first ray were found in all hands of this group. The adduction deformity was corrected by skin-plasty of the first web and the extension was improved by tendon transfers. Only one case needed stabilisation of the M.P. joint. The final results were related to the extent of the contractures and to the age of the patient when treatment started. PMID- 2926229 TI - The pronator quadratus sign: its classification and diagnostic usefulness for injury and inflammation of the wrist. AB - The clinical value of the pronator quadratus radiological sign was investigated. Fresh undisplaced fractures of the distal radius and acute injuries of the distal radio-ulnar joint showed anterior displacement of the radiolucent shadow in 85% and 88% respectively, but normal subjects no displacement. In rheumatoid arthritis, the presence of synovitis of the wrist joint appeared to be correlated with a blurred shadow at the distal end. PMID- 2926230 TI - Clenched fist human bite injuries. AB - A prospective study has been made of 29 human bite injuries caused by the clenched fist, 27 over M.P. joints and two over P.I.P. joints. All were treated by surgical exploration, within 24 hours in 84% of cases. In 62% the wound had entered the underlying joint and in 58% the bone was injured. Significantly less morbidity was noted in those cases where there was no joint injury (P less than 0.001). Early surgical exploration to identify and to treat the joint injury is recommended. PMID- 2926231 TI - Protothecosis following hand injury. A case report. AB - A case of protothecosis following an accidental cut on the dorsum of the hand by a fragment of glass from an exploding beer bottle is described. The area was widely excised and oral tetracycline given. No recurrence has been seen over a period of four years. PMID- 2926232 TI - Functional anatomy of the vagina fibrosa of the flexors of the fingers. AB - The flexor tendon sheaths of 40 fingers were investigated to determine which classification of the annular and cruciform pulleys seems to be justified. The classification of Kleinert et al. (1981) into five annular and four cruciform pulleys was the most consistent with our results. The constant presence of the mid-phalangeal annular pulleys in zones III and VII shows their major role in preventing the tendons from bow-stringing. The cruciform pulleys seem to allow the tendon sheath to deform during flexion. PMID- 2926233 TI - Surgical management of unresectable retroperitoneal leiomyosarcomas. AB - Retroperitoneal leiomyosarcomas are rare tumors with a poor prognosis. These tumors are often deemed unresectable because of their large size when diagnosed. This study presents two recent patients who show that retroperitoneal leiomyosarcomas can be resected successfully. Adjuvant radiotherapy is useful in treatment of patients with residual disease. Although the contribution of chemotherapy in prophylaxis and treatment of these tumors remains undefined, various chemotherapeutic regimens are currently under investigation. PMID- 2926234 TI - Interventional neuroradiology in the community hospital. AB - The active participation of the neuroradiologist in the therapy of neurosurgical patients is a concept with which many neurosurgeons as well as many radiologists are uneasy. Interventionally oriented radiologists have much to offer the neurosurgeon who accepts the radiologist as a partner in the management of patients with difficult problems. Technological advances in imaging, in guidewire and catheter design, and experience gained by radiologists and neurosurgeons have led to a number of therapeutic advances. We present several illustrative examples. PMID- 2926235 TI - Teaching medical students to use simple language when talking with patients. AB - Physicians know much about health and illness. The information is often complicated and difficult to understand. Part of the physician's task is to help the patient understand the information so that the patient may help himself. The accurate transfer of the information requires that physicians have excellent communication skills. One such skill is the ability to use language which is easily understood by the patient. This study suggests that, after preclinical medical students assume a formal teaching role in secondary schools, they are more likely to use simpler language when talking with patients during their final undergraduate year. PMID- 2926236 TI - ECG of the month. Ventricular bigeminal rhythm. PMID- 2926237 TI - Erythrocyte phospholipid organization and vesiculation in hereditary high red cell membrane phosphatidylcholine hemolytic anemia. AB - We have studied the erythrocyte membrane phospholipid organization in hereditary high red cell membrane phosphatidylcholine hemolytic anemia (HPCHA) and the response of these red cells during incubation with sonicated suspensions of dimyristoylphosphatidylcholine (DMPC). Although both the absolute and relative amounts of phosphatidylcholine were elevated in these red cells, the relative distribution of phosphatidylcholine on both sides of the membrane bilayer and the transbilayer mobility of phosphatidylcholine were normal. HPCHA erythrocytes showed elevated absolute amounts per cell of both protein and lipid and an increased cellular ratio of protein to phospholipid. Incubation of normal red cells with DMPC led to the formation of echinocytes, followed by the release of acetylcholinesterase-containing vesicles. Both echinocyte formation and vesiculation were markedly reduced in red cells from patients with HPCHA. Studies with red cells from patients with liver disease, cells that also have elevated relative amounts of membrane phosphatidylcholine and increased amounts of lipid per cell, revealed normal echinocyte formation and normal DMPC-induced vesiculation. We conclude that the altered lipid composition of HPCHA erythrocytes per se is not responsible for the observed reduction in DMPC-induced vesiculation, but that it is more likely the result of a modification in the protein moiety of these cells. This putative protein abnormality could enhance binding of phosphatidylcholine to red cell membranes and could explain the elevated phosphatidylcholine content of HPCHA erythrocytes and their inability to vesiculate. PMID- 2926238 TI - Neutrophil cathepsin G increases transendothelial albumin flux. AB - Neutrophils are involved in the development of inflammatory edema in some animal models, but their mechanisms of action are not completely understood. Among injurious agents available for neutrophil-mediated injury are cationic proteins such as cathepsin G. Previous articles have reported that cationic agents decrease the barrier properties of the endothelium both in vivo and in vitro. Using an ex vitro isolated, perfused rabbit lung and a cultured porcine pulmonary artery endothelial cell monolayer (ENDO) as models, we asked whether neutrophil cathepsin G could decrease the barrier properties of the intact vasculature and cultured endothelial monolayers. After the addition of cathepsin G (10 micrograms/ml) to the perfusate of the isolated, perfused lung, there was a fourfold increase in net weight gain after a venous pressure challenge (p less than 0.01). The addition of cathepsin G to a cultured ENDO directly increased the movement of albumin across the monolayers in a dose-dependent fashion (10 micrograms/ml led to a 59% +/- 5% increase, 15 micrograms/ml to a 135% +/- 55% increase, 20 micrograms/ml to a 247% +/- 78% increase, and 30 micrograms/ml to a 381% +/- 89% increase, p less than 0.05 at all concentrations). Heat-inactivation of the enzyme only partially protected the ENDO, but exposure in the presence of either the polyanion heparin or the polyanion dextran sulfate completely protected the ENDO. Normal human serum also protected the ENDO, but serum from two patients with alpha 1-proteinase inhibitor (alpha 1-PI) deficiency was only partially protective. The protection afforded by human serum was time dependent, because addition of the serum 5 or 15 minutes after the addition of cathepsin G offered no protection. Oxidation of alpha 1-PI, as may occur at sites of inflammation, also destroyed its protective effect. Cytotoxic injury of the porcine pulmonary artery endothelial cell monolayer by cathepsin G, which was also prevented by the polyanions, only partially explained these results, because cathepsin G increased albumin transfer across the ENDO at concentrations of 10 to 20 micrograms/ml, which were minimally cytolytic to the ENDO. Additionally, cathepsin G caused cell retraction, with the development of intercellular gaps visible on light microscopy of the ENDO. This effect was also prevented by the polyanions. These results demonstrate that cathepsin G has direct effects on a cultured ENDO that may be caused by the charge or charged site(s) on cathepsin G. PMID- 2926239 TI - Role of prostaglandins and thromboxane in the control of renal hemodynamics in experimental liver cirrhosis. AB - Although there is considerable evidence that vasodilator prostaglandins such as prostaglandin E2 (PGE2) modulate renal hemodynamics in liver cirrhosis, the role of the vasoconstrictor thromboxane A2 (TXA2) is controversial. We measured renal hemodynamics and glomerular eicosanoid production in cirrhotic and control rats. Renal plasma flow, as estimated by para-aminohippurate clearance (CPAH) and glomerular filtration rate, as determined by inulin clearance (CIN), were comparable between groups; glomerular production of PGE2 and TXA2 (estimated by the metabolite thromboxane B2 [TXB2]) was slightly but not significantly higher in cirrhotic than in control rats (PGE2: 1060 +/- 142 pg/mg glomerular protein vs 854 +/- 288 pg/mg glomerular protein; TXB2: 782 +/- 103 pg/mg glomerular protein vs 468 +/- 104 pg/mg glomerular protein). Addition of serum from cirrhotic rats to the incubation media failed to increase eicosanoid production in glomeruli obtained from either cirrhotic or control rats. Cyclooxygenase inhibition with 5 mg/kg indomethacin, a dose sufficient to result in a 68% inhibition of glomerular PGE2 synthesis, decreased both CPAH (from 6.59 +/- 0.69 ml/min to 4.52 +/- 0.67 ml/min, p less than 0.05) and CIN (from 1.34 +/- 0.16 ml/min to 0.68 +/- 0.07 ml/min, p less than 0.01) in cirrhotic rats. Thromboxane synthesis inhibition with 1 mg/kg UK-38485, which resulted in an 84% decrease in glomerular TXB2, did not significantly affect either CPAH or CIN; however, there was a strong trend toward improvement in CIN (from 1.23 +/- 0.11 ml/min to 1.43 +/- 0.15 ml/min (0.05 less than p less than 0.1). Neither drug affected renal hemodynamics in control rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2926240 TI - Cholesterol guidelines, lipoprotein cholesterol levels, and triglyceride levels: potential for misclassification of coronary heart disease risk. AB - By using National Cholesterol Education Program guidelines for serum cholesterol (less than 200 mg/dl is designated "desirable," and 200 to 239 mg/dl is designated "borderline-high," and greater than or equal to 240 mg/dl is designated "high"), low-density and high-density lipoprotein (LDL, HDL) cholesterol levels and triglyceride levels were quantitated in 897 self-referred fasting subjects to assess the potential for coronary risk misclassification. With cholesterol less than 200 mg/dl, misclassification was arbitrarily identified by an LDL level greater than or equal to the 75th percentile, a triglyceride level greater than or equal to the 90th percentile, or an HDL level less than or equal to the 10th percentile. With the cholesterol level in the 200 to 239 mg/dl range, misclassification was identified by an LDL level greater than or equal to the 75th percentile, a triglyceride level greater than or equal to the 90th percentile, and an HDL level less than or equal to the 10th percentile or greater than or equal to the 90th percentile (or both). With a cholesterol level greater than or equal to 240 mg/dl, misclassification was identified by an HDL level less than or equal to the 10th percentile, or greater than or equal to the 90th percentile. With the cholesterol level less than 200 mg/dl, misclassification is rare, occurring in 14.5% of the subjects. With the cholesterol level in the 200 to 239 mg/dl range, and greater than or equal to 240 mg/dl, misclassification occurred in 46.7% and 17.6% of the subjects, respectively. The importance of routine lipoprotein analysis when the cholesterol level is greater than or equal to 240 mg/dl is emphasized by the finding that 65% of the subjects in this category had top quartile LDL levels, 8% had bottom decile HDL levels, and 30% had top decile triglyceride levels. To avoid misclassification, fasting HDL, LDL, and triglyceride levels should probably be measured in all subjects with screening cholesterol levels greater than or equal to 200. There is remarkably little misclassification with top quartile LDL or bottom decile HDL levels (or both) when the cholesterol level is less than 200 mg/dl. PMID- 2926241 TI - Characterization of a novel myeloma cell line, MM.1. AB - A myeloma cell line, MM.1, has been established from the peripheral blood cells of a patient with immunoglobulin A myeloma. MM.1 grows in suspension either singly or in small clusters and secretes lambda-light chain. Phenotypically, MM.1 cells lack most B cell antigens, but they do express human leukocyte antigen DR, PCA-1, and T9 and T10 antigens. Molecular analysis of MM.1 demonstrates that it is negative for the presence of the Epstein-Barr virus genome. Southern analysis of MM.1 detected a rearrangement of the lambda-light chain gene, and Northern analysis revealed high levels of lambda gene expression. Cytogenetic analysis of the MM.1 cell line revealed the presence of seven related chromosomally abnormal cell lines characterized by numerical and structural aberrations, and it revealed five nonclonal abnormal cells. The most notable abnormality is a reciprocal translocation involving band q24.3 of chromosome 12 and band q32.3 of chromosome 14; translocations involving 14q32 are frequently observed in neoplasms of B cell origin. PMID- 2926242 TI - Hepatocyte iron release in rats. AB - Hepatocyte iron release was studied in vivo in rats. After the injection of iron 59-labeled ferritin, hemoglobin, or human asialotransferrin, the proportions of the radioactive iron returned to the plasma and incorporated into stores were determined under various conditions. Iron 55-labeled rat transferrin was injected at the same time as the 59Fe-labeled compound, and storage iron release was calculated from the cumulative incorporation of the two isotopes in the red cell mass over 2 weeks. The various 59Fe-labeled compounds were processed differently by the hepatocyte, but the radioactive iron was incorporated in the same iron stores. About 6% of the hepatocyte storage iron was released daily in normal rats, but a pool of iron that is not mobilized spontaneously was clearly identified in iron overload. Iron turnover in the hepatocyte was regulated by the rate of erythropoiesis and iron status of the animal, and inflammation blocked hepatocyte iron release. A strong correlation between hepatocyte iron release and plasma transferrin receptor levels was observed (p less than 0.001), suggesting that plasma transferrin receptors could mediate the regulation of hepatocyte iron mobilization in rats. PMID- 2926243 TI - Effect of neutrophil depletion on ischemic renal injury in the rat. AB - Oxygen free radicals have been implicated in postischemic renal injury. However, the source of these oxygen free radicals has not been well defined. One potential source is activated neutrophils. Neutrophil depletion was produced in rats by using two different techniques, and the effect on ischemic injury was examined. Rabbit anti-rat neutrophil serum was prepared by immunizing a rabbit with a Percoll gradient centrifugation-purified (approximately 90%) suspension of rat neutrophils. Rats received antineutrophil serum in one of four protocols and were subsequently subjected to 40 minutes of renal artery occlusion. Control animals received nonimmune rabbit serum. The serum creatinine levels 24 hours after ischemia were not different between control and immune serum-treated rats in any of the protocols despite significant reductions in absolute neutrophil count. In a separate study, nitrogen mustard was administered 40 hours before ischemia. Nitrogen mustard-treated rats developed moderate neutropenia and 24 hours after ischemia had lower serum creatinine levels and higher inulin clearance. However, nitrogen mustard-treated rats lost 31.5 +/- 5 gm body weight in the 2 days after nitrogen mustard administration, whereas control animals gained 5.9 +/- 5.9 gm during the same interval. Furthermore, among nitrogen mustard-treated rats there was no correlation between neutrophil count and postischemic renal function. It is thus possible that the beneficial effects of nitrogen mustard were caused by a mechanism other than neutrophil depletion. In summary, in four protocols that used antineutrophil serum, neutropenia did not protect against ischemic injury. Nitrogen mustard provided protection, but probably by a neutrophil-independent mechanism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2926244 TI - Symptomatic hypercalcemia pulmonary tuberculosis. AB - We describe a case of active pulmonary tuberculosis whose care was complicated by the onset of severe hypercalcemia that manifested after the institution of standard antituberculous therapy. We review the knowledge regarding the association of hypercalcemia with active pulmonary tuberculosis and present the proposed mechanisms for the pathogenesis of the disorder. PMID- 2926245 TI - Arterial bullet embolism. AB - We report a case of an arterial bullet embolus and compare it with other cases found in the literature. A 27-year-old white male sustained a .22 caliber gunshot wound that penetrated the abdominal aorta and traveled within the arterial system to occlude the left superficial femoral artery. The case was typical in that projectiles that embolize within the vascular system originate as a low kinetic energy missile injury of the trunk. Atypically, the patient developed ischemic changes from the embolus immediately. After direct aorta repair and immediate transverse arteriotomy bullet removal, the patient recovered fully. PMID- 2926246 TI - Subglottic tuberculosis: a case report. AB - Granulomatous disorders of the larynx can take on many forms and usually represent the end stage of chronic disease. In the past, laryngeal granulomas were much more prevalent primarily because of the frequency of tuberculosis. Seldom is the larynx the site of origin for granulomatous disease, but it is usually a manifestation of a pulmonary entity such as histoplasmosis, blastomycosis, sarcoidosis, or tuberculosis. The actual diagnosis is frequently arrived at while trying to rule out carcinoma. Laryngeal tuberculosis, although rare in the United States, remains the most common granulomatous disease of the larynx. Its increasing incidence has paralleled the diminished incidence of tuberculosis in the general population. Specific clinical characteristics for diagnosis are few and diagnosis is arrived at through a high index of suspicion and biopsy. When biopsy is carried out, adequate tissue should be obtained for both histological sections, cultures, and sensitivities. PMID- 2926247 TI - Maternity leave and job security: a prescription for improved quality of life in the USA. PMID- 2926248 TI - Common gastrointestinal problems in the elderly. AB - Despite advances in our knowledge about the pathogenesis of gastrointestinal disease, very little is known about the effects of aging on the gastrointestinal tract. We believe that the spectrum of gastrointestinal problems of the elderly and possible therapies for these problems will be the subjects of many future investigations. PMID- 2926249 TI - Our child survived unharmed. PMID- 2926250 TI - KMA first recipient of the AMA President's Citation for Service to the Public. PMID- 2926251 TI - Interprofessional code. Kentucky Medical Association and Kentucky Bar Association. PMID- 2926252 TI - Regional differences in death rates among postneonatal infants in Kentucky, 1982 1985. AB - Our objective was to analyze differences in postneonatal mortality rates between the southeastern (Appalachian) region of Kentucky and the remainder of the state to identify factors associated with increased mortality in the Appalachian (AP) region. The relative risk of postneonatal deaths in the AP region when compared with the remainder of Kentucky (KY) was 1.38 (95% confidence interval = 1.15 1.65). Adjustment for birth weight, maternal age, and marital status of the parents had no appreciable effect on the risk ratio; however, adjustment for maternal education negated the increased risk of postneonatal death among the AP region births. When causes of postneonatal death were compared, three specific disease groupings were disproportionately represented among AP infants: Sudden Infant Death Syndrome (SIDS); congenital malformations; and infections. Most striking was the excess risk of infection-related death because it represents a preventable component in the postneonatal mortality excess of the AP region; and, because of the apparent association with maternal "under education." These findings are discussed within a public health intervention context. PMID- 2926253 TI - The adult nonsurvivor of child abuse. AB - There is a growing clinical research interest in the long-term effects of victimization in childhood and the difficulty the victimized child may experience in adulthood. Examined are two case illustrations of individuals who were abused as children. The results of their dysfunctional childhood have yielded massive failures to cope and adjust to adult stress situations and have resulted in each case with the development of psychopathology that has impaired their adult lives. Issues and import for clinical practice and future research are discussed. PMID- 2926255 TI - Who said quality control? PMID- 2926254 TI - Hematuria--harbinger of cancer. AB - The complaint of blood in the urine or the finding of unexpected microscopic hematuria continues to be an important diagnostic clue to the presence of carcinoma of the urinary tract. Inadequate evaluation of this complaint or finding may lead to a delay in diagnosis and progression of disease. A thorough evaluation of the urinary tract with intravenous pyelography, urinary cytology, and cytoscopy is necessary. PMID- 2926256 TI - Observation of the glycocalyx of the organ of Corti: an investigation by electron microscopy in the normal and gentamicin-treated guinea pig. AB - The ultrastructure of the glycocalyx of the organ of Corti in the normal and gentamicin-treated guinea pig was investigated at the electron microscopic level by using the ruthenium red staining technique. The glycocalyx was evident over the whole apical surface of both sensory and supporting cells. The entire length of the stereocilia of both inner and outer hair cells was seen to be covered by a glycocalyx, which interconnected the neighbouring stereocilia. In the gentamicin treated animals, the fusion process between the stereocilia was revealed and a decrease of the glycocalyx was noticed at the point where fusion started. These findings suggest that the glycocalyx may play an important role in holding the stereocilia together in a bundle, yet prevent their close contact by means of its strong negative charge. PMID- 2926258 TI - Staging in cholesteatoma surgery. AB - Single stage surgery was used for 174 operations for cholesteatoma. The results were analysed using months at risk (actuarial) statistics. The methods of data collection and of creating a life-table for cholesteatoma follow-up are described. Ninety-one canal-down procedures are compared with 82 canal-up procedures as to the recidivism rate as well as hearing results. The actuarial tables showed a 50 per cent cumulative success rate for canal-up procedures versus a 90 per cent rate for canal-down operations. The successful canal-up procedures, however, demonstrated slightly better hearing results. These success rates seemed to be comparable to those using planned staged surgery. It was concluded that if single stage canal-up procedures were used with larger mastoids and canal-down procedures with smaller mastoids, 80 per cent of patients could be controlled without either residual or recurrent disease appearing. For the others, it was felt safe to wait for the disease to reappear rather than to do planned two-stage procedures for all patients. It was further urged that actuarial statistics be employed when reporting the results of surgery for cholesteatoma. PMID- 2926257 TI - Carbohydrate content of the endolymphatic sac. A histochemical and lectin labelling study in the Mongolian gerbil. AB - A secretory activity has recently been attributed to the endolymphatic sac (ES), as a possible way to contribute to the fluid balance of the entire endolymphatic compartment. Previous histochemical studies have indicated the existence of carbohydrate complexes in the secretory product, both neutral and acidic in nature. A thorough analysis of these compounds in the gerbilline ES was carried out using both transmission electron microscopic (TEM) histochemistry, using dialyzed iron and periodic acid--chromic--silver staining techniques, as well as immunoflourescence with fluorescein-labelled lectins (FITC-lectins). N acetylglucosamine was found to be one of the major carbohydrate components both of the epithelial layer of the ES and of the luminal precipitate. Proofs for a local secretory activity and its intracellular pathway are presented, suggesting to be involved in the regulation of pressure and volume of inner ear fluids. PMID- 2926259 TI - Tensa retraction cholesteatoma: treatment and long-term results. AB - To obtain the best possible results of treatment of acquired cholesteatoma, we made a subdivision of cholesteatoma types into attic and pars tensa cholesteatomas, and subdivided the latter further into tensa retraction cholesteatoma and sinus cholesteatomas. Tensa retraction cholesteatoma is defined as arising from a retraction or perforation of the whole pars tensa, whereas sinus cholesteatoma is defined as arising from a retraction or perforation of the postero-superior part of the tensa. We present the long-term results obtained in tensa retraction cholesteatomas treated with one stage surgery from 1964 to 1980. Median observation time was 9 years, range 2 to 19 years. Sixty-one ears were treated without mastoidectomy, whereas 71 ears had canal wall-up mastoidectomy and 64 ears had canal wall-down mastoidectomy. The total recurrence rate was 13.3 per cent; 17 ears had residual cholesteatoma, and nine ears had recurrent cholesteatoma. The best results were obtained in ears with an intact ossicular chain where mastoidectomy was not performed. In 49 per cent of the cases, the cholesteatoma was confined to the tympanic cavity without reaching the aditus, antrum or mastoid process. About one-third to one-quarter of the ears had tympanoplasty only, with removal of the cholesteatoma through the ear canal. PMID- 2926260 TI - Sensorineural hearing loss in chronic otitis media. AB - A statistical study was done on the sensorineural component in hearing loss, using 595 patients suffering from Chronic Otitis Media (COM); of these, 195 with monolateral COM were taken into consideration. They presented criteria of valuation which excluded other possible causes of sensorineural hearing loss, such as exposure to acoustic trauma, ototoxic drugs, cardiovascular disease, past head injury and hereditary causes. The contralateral (healthy) ear served as a control. We determined the average sensorineural component in the hearing losses in relation to the age of onset and duration of the disease, examining it in relation to other eventual aural complications such as cholesteatoma. On the basis of the data obtained, we believe that the sensorineural component in hearing loss does not change with respect to the age of onset of COM, but the duration of COM does exert a significant influence. PMID- 2926261 TI - Hearing threshold in patients with diabetes mellitus. AB - Hearing threshold of 30 diabetic patients and 30 healthy controls attending the medical outpatient department were determined using pure tone audiometry (Arphi Digital 900). All subjects were less than 50 years old. Subjects with otological and other metabolic diseases were excluded from the study. The patients were categorized into groups according to age, duration of disease, complications and control of diabetes. These observations were compared with those from the control subjects using appropriate statistical methods. It was found that diabetics had a poorer hearing threshold than the non-diabetics; all age groups with diabetes showed a significant high frequency hearing loss, as compared to the control population; poorly controlled and complicated diabetics have significant, high frequency hearing loss as compared to those who were well controlled and uncomplicated; there was no relationship between duration of the diabetes and the level of hearing loss. PMID- 2926262 TI - Facial nerve recovery after acoustic neuroma removal. AB - A retrospective analysis of 76 patients who underwent acoustic neuroma removal is reported. Facial nerve function prior to surgery and tumour size are assessed with respect to final facial nerve recovery and the need for surgical rehabilitation. Both pre-operative facial weakness and tumour size greater than 2.5 cm. are shown to be predictive factors of poor facial nerve recovery. Multiple surgical rehabilitative procedures are often required when inadequate function and/or cosmetic results are obtained. Primary nerve repair and facial hypoglossal anastomosis give better rehabilitative results than dynamic and static procedures. The association of tumour size greater than 2.5 cm. with increased risk of poor facial recovery re-emphasizes the need to detect and remove acoustic neuromas at an early stage. PMID- 2926263 TI - CT air meatography: review of side effects in 60 patients. AB - Sixty patients investigated for a suspected acoustic neuroma were questioned on the side effects of CT air meatography, a minimum of three months following the procedure. Twelve per cent of patients found the procedure itself so painful that a repeat examination would only be contemplated under general anaesthesia. Only 20 per cent of patients were asymptomatic after the procedure while 28 per cent of patients required bed rest for 24 hours or more (average 4.4 +/- 2.8 days). Sixty-two per cent of patients took three days or longer to return to normal health. The duration and frequency of side effects is greater than previously reported, and emphasizes the need for full investigation of these patients prior to CT air meatography. PMID- 2926264 TI - Tonsillar microflora--superficial surface vs deep. PMID- 2926265 TI - Culture of Rhinosporidium seeberi: preliminary report. AB - Every year 400 to 450 cases of Rhinosporidium are reported from Trivandrum Medical College. Twenty-five swabs were collected from patients suffering from Rhinosporidiosis and cultured in standard media. Positive results were obtained in 23 cases. The conidia produced from the colony were compared with the structures obtained from the patient material. Light microscopy using histopathological techniques were used. The consistent appearance of the organism in patient material, the repeatability of growth in subcultures and the negative growth in controls indicated that the organism grown in culture is the causative agent of the disease. The effect of parameters like pH, temperatures, etc, were also studied. PMID- 2926266 TI - Total parotidectomy--a routine treatment for parotid gland swellings? AB - The results of 25 years of quasi-routine total parotidectomy performance are shown. At the Department of Otolaryngology of the University of Florence, 582 patients were treated as follows: on 527 occasions by total parotidectomy with facial nerve preservation; 24 occasions by lateral lobectomy; 27 occasions by total parotidectomy with removal of the whole facial nerve; four times by enucleo resection of the disease. Benign tumours were 378; primary and metastatic malignant tumours--100; non tumoral lesions--104. The benign tumours follow-up showed three recurrences only (two pleomorphic adenomas--one of them proved to be an adenoid-cystic carcinoma, and one monomorphic adenoma, which also proved to be an adenoid-cystic carcinoma), respectively 6, 6 and 8 years later. The malignant tumours were also treated by total parotidectomy with adequate management both of the facial nerve and the neck lymph nodes. The results thoroughly justify the nerve preservation, when preserved. PMID- 2926267 TI - Effect of weather conditions on acute laryngotracheitis. AB - The aim of the study was to examine the incidence of croup in the Swansea area and to determine whether meteorological factors have any effect on the incidence of acute laryngotracheitis requiring hospitalization. 447 patients with a diagnosis of acute viral croup were admitted to the Ear, Nose and Throat Department of Singleton Hospital, Swansea, between January 1st 1980 and December 31st 1984. There was no significant difference between days with and without croup admissions, with respect to barometric pressure or relative humidity. Maximum and minimum temperatures were significantly lower on days with croup admissions (p less than 0.001). Wind direction appeared to influence the number of admissions, which were increased when the wind was from the south-east (p less than 0.01). PMID- 2926268 TI - Cricothyroid muscle paralysis: its recognition and diagnosis. AB - Cricothyroid muscle paralysis is often missed as the symptoms are not dramatic and the laryngeal observations, on conventional indirect mirror examination, are inconclusive. The anatomy and physiology of the superior laryngeal nerve (SLN) and cricothyroid muscle are described. Three case reports are presented to illustrate our diagnostic techniques. Videofibrolaryngoscopy and electromyography are found to be invaluable tools for the diagnosis of this condition. The importance in diagnosing this entity is discussed. PMID- 2926269 TI - Chronic aspiration and laryngeal competence. AB - Aspiration into the lower respiratory tract can be detrimental to life. Ten patients, suffering from neurological dysphagia with aspiration, were studied. Neurological disorders can cause inadequate glottic closure resulting in aspiration. It has not been well recognized however, that even patients who have full glottic closure are still capable of aspirating in the pre- and post deglutition stages of swallowing. The combined techniques of videofibrolaryngoscopy and videofluoroscopy are found to be the best methods for demonstrating these abnormalities. Development of new techniques, in the prevention of aspiration, should also take into account silent, pre- and post deglutitional aspiration. PMID- 2926270 TI - Benign paroxysmal positional vertigo resulting from surgical trauma. AB - A patient developed benign paroxysmal positional vertigo following partial excision of the upper jaw for squamous carcinoma. It is probable that the trauma sustained by the labyrinth during surgery led to the development of vertigo. Benign paroxysmal positional vertigo may be a preventable post-operative complication. PMID- 2926271 TI - Aberrant reinervation of the stapedius muscle following facial palsy. AB - This case report describes the clinical course of a patient with Ramsay Hunt Syndrome. Partial recovery of the lower motor neuron facial palsy was associated with decreased hearing and a reduction of the middle ear compliance on voluntary contraction of the facial musculature. It is suggested that this is due to misdirection of regenerating nerve fibres, normally destined for facial muscles, to stapedius muscle. PMID- 2926272 TI - Haemorrhage during minitracheotomy: reduction of risk by altered incision. AB - A 46-year-old male was admitted to an intensive care unit: for 11 days he waa ventilated via a naso-tracheal tube. Because of excess tracheal secretions, a mini tracheotomy was attempted on the unit which resulted in profuse arterial haemorrhage, necessitating immediate reintubation and subsequent formal tracheostomy. The authors feel that this complication was due to a mid-line vertical incision and that this could have been avoided by a horizontal incision across the lower part of the cricothyroid membrane, as close to the cricoid cartilage as possible. They describe their recommended technique. PMID- 2926273 TI - Pedunculated squamous papilloma of the laryngopharynx. AB - Pedunculated squamous papillomas usually arise from the soft palate, tonsil or the epiglottis. These lesions can sometimes prove to be fatal. A case of pedunculate squamous papilloma, arising from the laryngopharynx, in a young, mentally retarded female, is presented here. The clinical presentation, the site of origin and the size of the lesion were quite unusual. The narrow base of the pedicle made the intra-oral excision possible. PMID- 2926274 TI - Metastatic bone marrow involvement from supraglottic squamous cell carcinoma. AB - A case of an aggressive supraglottic squamous cell carcinoma, which was managed with neo-adjuvant chemotherapy and radical surgery, is described. The post operative course was of rapid deterioration and death due to progressive metastatic disease involving bone marrow and liver. This is the first reported case of bone marrow infiltration by squamous cell carcinoma of the head and neck diagnosed ante-mortem. The incidence and pattern of metastatic disease from head and neck tumours is reviewed, and the importance of initial staging in determining the risk of distant metastatic disease is emphasised. PMID- 2926275 TI - Breast metastasis from a pharyngeal carcinoma. AB - The reported incidence of metastatic disease in head and neck cancer is increasing. The most common site of metastatic involvement in squamous carcinoma of the head and neck is the lung followed by liver, mediastinal nodes and bone. The breast is rarely infiltrated by metastatic disease, 2 per cent or less of clinically detected breast lumps being of non-mammary origin, most frequently malignant melanoma, lymphoma/leukaemia and primary lung carcinoma. A 73-year-old female presented with a primary posterior pharyngeal wall squamous carcinoma and bilateral enlarged neck nodes. She developed an isolated breast metastasis while receiving palliative radiotherapy and died seven months after presentation. Clinically detected breast metastasis in head and neck squamous cell carcinoma was first documented by Toombs and Kalisher in 1977. This is the first report of such a case originating in the posterior pharyngeal wall. The prognosis is invariably poor. PMID- 2926276 TI - Tetanus presenting as dysphagia. PMID- 2926277 TI - Malignant melanoma of the nasal cavity. AB - Primary mucosal melanoma of the head and neck is rare and few published cases give proof that the mucosal site is primary. We present a man with malignant melanoma of the nasal cavity which was associated with melanoma-in-situ of the adjacent mucosa, proving that the lesion was primary. He presented with symptoms due to secondary deposits of melanoma in the brain rather than the more usual nose bleeds or blocked nose. The primary site was found when his neurological symptoms were investigated by CT and NMR scans of the head. PMID- 2926279 TI - Parotidectomy--total or superficial? PMID- 2926278 TI - Haemangiopericytoma of the larynx. AB - Haemangiopericytoma is an uncommon vascular tumour which has rarely been recorded in the larynx. The diagnostic and histopathological difficulties are discussed. A total laryngectomy was performed because of the size and site of the tumour, the associated risk of local recurrence and the high metastatic rate. PMID- 2926281 TI - Neutral lipid accumulation in macrophages during lipid-induced macrophage growth. AB - We previously reported that lipids such as cholesterol esters, triglycerides, and some phospholipids that are components of cell membranes or serum lipoproteins induced the growth of mouse peritoneal macrophages in vitro. Here, we report that macrophage growth was directly induced by lipids without any soluble factors and that the continuous presence of lipids was required for their growth during culture. When macrophages were cultured with several phospholipids that stimulated macrophage growth, their triglyceride content was dramatically increased during culture, whereas their contents of phospholipids, cholesterol, and esterified cholesterols were scarcely changed. On the other hand, phosphatidylcholine and sphingomyelin, which did not stimulate macrophage growth, caused less accumulation of triglycerides in the cells. Macrophages in which triglycerides accumulated resembled foam cells, since they contained many particles that stained with oil red O. Macrophages that cultured with cholesteryl linoleate also contained many oil red O-stainable particles. These data suggest that accumulation of lipid droplets is correlated with macrophage growth induced by lipids and that foam cells in pathological states such as those in atherosclerotic or xanthoma lesions might proliferate in situ. PMID- 2926280 TI - Phorbol ester-induced loss of membrane sialic acid: implications for tumor cytolysis by natural killer cells. AB - Freeze-fracture analysis has shown that treatment of cells with phorbol myristate acetate (PMA) results in a loss of intramembranous particles (IMP) associated with the external leaflet of their plasma membranes. It has also been demonstrated that phorbol esters markedly enhance the sensitivity of tumor targets to natural killer (NK) cells, although the mechanism underlying this phenomenon has remained unexplained. Since the ability of NK cells to recognize neoplasms appears to be inversely related to the concentration of sialic acid on the target cell surface, it seemed possible that phorbols affect membrane glycoproteins which have terminal carbohydrates bearing sialic acid residues. To investigate whether phorbol treatment could be responsible for the loss of sialic acid, four tumor cell lines were examined before and after exposure to PMA. A reduction in surface sialic acid was established by four different methods: 1) standard thiobarbituric acid analysis of cell hydrolysates, 2) metabolic labelling of cells with [3H]-mannosamine followed by treatment with neuraminidase, 3) chromatography of membrane extracts, and 4) freeze-fracture analysis of lectin-labelled intact cells. These observations suggest a mechanism whereby phorbols may facilitate NK-cell-mediated cytolysis. In addition, an entirely novel effect of these tumor-producing agents may have been uncovered. PMID- 2926282 TI - Editorial freedom and the JMPT. PMID- 2926283 TI - Clinical competence: the use of simulators/models in diagnosis of visceral conditions. AB - As primary contact practitioners, chiropractors must be competent to screen patients for the presence of visceral disease. Special "clinical" preparation is required to provide students with adequate diagnostic skills in this area in view of the "select" group of patients frequenting chiropractic clinics--the vast majority of chiropractic patients present with musculoskeletal disorders or pain syndromes. The use of sound simulators and life-form models in a problem-based teaching format ensures that students are equipped to cope with any primary contact clinical eventuality in this area. The use of these sound simulators and models in the assessment of clinical competence furthermore enables the implementation of improved standardization and clinical relevance in clinical assessment. PMID- 2926284 TI - Skin accelerometer displacement and relative bone movement of adjacent vertebrae in response to chiropractic percussion thrusts. AB - The authors studied relative bone movements in response to manipulative light taps to the spine. Piezoelectric accelerometers attached to bone of an anesthetized dog measured transverse, X-Z plane, movements of L2-L3 adjacent vertebrae while percussion thrusts of an instrument used for manipulation made inputs three vertebrae above and five vertebrae below the L2-L3 joint interface. Small, relative 1-mm translations and 0.5 degree rotations occurred during the first 19 msec. When one set of accelerometers were stabilized on the skin surface, half of the skin-bone translation maxima erred less than 2%. However, skin translations averaged 77% (SD = 2%) of bone translations and skin rotations averaged 95% (SD = 26%) of bone rotations. The results suggest the possibility that, with further development, piezoelectric accelerometers can be a noninvasive tool to study dynamic, relative, bone movement. PMID- 2926285 TI - Limb segment information transmission capacity. AB - Movement time for finger, wrist, and whole arm motions were investigated in relation to Fitts' Index of Difficulty (ID = log2 2A/W) over movement distances of 0.25 to 30.5 cm. Results supported Fitts' original theory that various limb segments may show different maximum information processing rates. Short-distance finger and wrist motions showed much higher rates than longer distance arm motions. Examination of motion trajectories qualitatively supported a descriptive model whereby a visually mediated discrete correction control process is used. However, evidence of severe nonlinearities in the measured humam movement responses did not support the use of linear control models in explaining the empirical validity of Fitts' law in predicting human motor performance. PMID- 2926286 TI - Osteochondrosis of the tibial tuberosity (Osgood-Schlatter's disease) AB - A case is presented of arthralgia of the left knee associated with osteochondrosis of the tibial tuberosity (Osgood-Schlatter's disease). Orthopedic findings included normal active ranges of knee flexion and extension, but pain with passive flexion and extension movements. Radiographic findings included the presence of slight prominence of the soft tissue overlying the tibial tuberosity. Initially, management of this case consisted of conservative therapy to alleviate pain, inflammation and swelling. Subsequent treatments were designed to result in complete recovery from any discomfort in the knee joint/muscle/ligaments complex. PMID- 2926287 TI - Viability of small-scale clinical research centers. PMID- 2926288 TI - Chondromalacia patellae. PMID- 2926289 TI - Radiogenic cancer induction associated with spinal radiography: a quantitative analysis. PMID- 2926290 TI - Effects of a chiropractic adjustment on changes in pupillary diameter: a model for evaluating somatovisceral response. PMID- 2926292 TI - Thermographic imaging of myofascial trigger points. PMID- 2926291 TI - Pharmacological modulation of localized inflammatory reactions: the nonsteroidal anti-inflammatory drug as an adjunct to therapy. PMID- 2926293 TI - A critical look at the subluxation hypothesis. PMID- 2926294 TI - Growth hormone increases plasma levels of insulin-like growth factor (IGF-I) in a teleost, the gilthead seabream (sparus aurata). AB - A heterologous radioimmunoassay (RIA) was applied for the determination of immunoreactive (IR)--insulin-like growth factor (IGF-I) in a teleost, the gilthead seabream (Sparus aurata). Serial dilutions of the fish plasma gave a linear curve when added to constant amounts of 125I-labelled human IGF-I(53-70) and antiserum prepared against this fragment. The RIA was used to study the effect of GH on plasma levels of IR-IGF-I in S. aurata. A single injection of human recombinant GH (1 micrograms/g) resulted in a significant increase in IR IGF-I at 29, 48 and 72 h, when compared with saline-injected fish. This novel observation suggests that in fish, as in mammals, circulating IGF-I levels are modulated by GH. PMID- 2926295 TI - Effect of exogenous prolactin and bromocriptine on seasonal reproductive quiescence in the Bennett's wallaby (Macropus rufogriseus rufogriseus). AB - Two experiments were performed to investigate whether prolactin blocks the reactivation of the corpus luteum during seasonal reproductive quiescence in the Bennett's wallaby. In the first experiment three groups of non-lactating females (groups A C) were subjected in mid-April to photoperiods corresponding to those of the summer solstice from day 0 to day 13 of the experiment. Between days 14 and 52, photoperiods were reduced to correspond to those of the winter solstice (groups B and C). Animals in group A were maintained on the long photoperiods. Two milligrams ovine prolactin (groups A and C) or vehicle (group B) were administered on the mornings of days 14-22. In group A, no animal showed evidence of an active corpus luteum based on increased plasma progesterone levels. All animals in groups B and C exhibited reactivation of the corpus luteum. In group C, reactivation was significantly (P less than 0.01) delayed by a mean of 6.3 days. In the second experiment, two groups of nonlactating female wallabies in 'seasonal quiescence' were injected daily for 7 days with either 60 mg of the dopamine agonist bromocriptine or vehicle. The corpora lutea did not reactivate in either group. We conclude that exogenous prolactin is able to block the effect of short photoperiods in reactivating the quiescent corpus luteum during seasonal quiescence. However, the absence of an effect of bromocriptine suggests that if prolactin is the endogenous hormone responsible for maintaining seasonal quiescence it may not be under dopaminergic control at this time of year. PMID- 2926296 TI - Multiple forms of rat prolactin and growth hormone in pituitary cell subpopulations separated using a Percoll gradient system: disulphide-bridged dimers and glycosylated variants. AB - Prolactin and GH cells from rat pituitary glands were separated into three main fractions on discontinuous Percoll gradient layers. SDS-PAGE and subsequent immunoblotting of these fractions revealed that: (1) multiple rat prolactin (rPRL) molecular variants were present in total culture, Percoll layer 1 and 2; four variants were clear-cut: Mr approximately 23,000, Mr doublet approximately 25,000-26,000, Mr approximately 40,000 and Mr approximately 42,000; (2) cell cytosol from Percoll gradient layer 1 was particularly enriched in prolactin; (3) cells from gradient layer 1 secreted into the culture medium only prolactin in detectable amounts; (4) three distinct molecular forms of rat growth hormone (rGH) were recorded in layer 3: Mr approximately 36,000, 24,000 and 20,000; the 20,000 variant was paramount; and (5) cells from layer 3 secreted both rPRL and rGH into the culture medium. Reduction experiments showed that, on the one hand, 42,000 and 40,000 rPRL variants and, on the other hand, 36,000 rGH variants are disulphide-bridged dimers. An important finding was the presence of glycosylated rPRL and rGH: indeed Concanavalin A-Sepharose 4B affinity chromatography indicated that 26,000 rPRL and 24,000 rGH display a very strong affinity for lectin. Competitive inhibition tests showed that this affinity is specific and not due to hydrophobic binding. When rPRL was submitted to deglycosylation in conditions specific for O-linked glycoproteins, the 26,000 rPRL variant disappeared. The biological role of glycosylated rPRL is as yet unknown. PMID- 2926297 TI - Steroids in equine testes: the identification of endogenous 19-hydroxy and 19-nor neutral steroids by gas chromatography--mass spectrometry. AB - After homogenization of testicular tissue from stallions aged 1, 2 and 5 years, the unconjugated and conjugated steroids were isolated by a combined solvent solid extraction procedure. The conjugates were further separated into glucuronides and sulphates by chromatography using Sephadex LH-20. After enzyme hydrolysis and solvolysis of the respective conjugate classes, the three extracts, unconjugated steroids, aglycones and solvolysed sulphates, were purified by chromatography using Kieselgel 60H columns. Five fractions were resolved from each extract; an aliquot of each fraction was derivatized to form the methoxime-trimethylsilyl ethers and the steroids were identified by combined gas chromatography-mass spectrometry. The results have shown that in stallion testes (1) steroidogenesis proceeds by both the 4-ene and the 5-ene pathways, (2) age-linked changes occur in both unconjugated and sulphoconjugated steroid fractions and (3) 19-hydroxy androgens and the 19-nor (C18) neutral steroids (19 norandrostenedione and 19-nortestosterone) are detected only in the unconjugated fraction whereas oestrene, the isomers of oestradiol and of 5(10)-oestrene-3,17 diol are the only steroids detected in the sulphoconjugate fraction. It is suggested that the unconjugated 19-oxygenated androgens present in stallion testes are converted to 19-nor neutral steroids by a reverse aldol reaction and a mechanism showing the putative intermediates in their formation is illustrated. PMID- 2926298 TI - Stabilization, accurate determination, and purification of rat liver nuclear thyroid hormone receptor. AB - Rat liver nuclear thyroid hormone receptor lost 3.5.3'-tri-iodo-L-thyronine (T3) binding activity with a half-life of 14 days, 4h, 139 min, 62 min, 16 min or 6 min at 0, 36, 38, 40, 43 or 45 degrees C respectively, when present in crude nuclear extracts. Glycerol increased the half-life of the receptor during heat inactivation. Protection was reversible by removing the glycerol. The receptor was unstable at a pH below 6.0 or above 10.0. We also found a loss of the receptor activity during the separation of bound and free hormone using the resin test. Of several conditions tested for the separation of bound and free hormone, the addition of heated nuclear extract gave the most accurate estimation of bound hormone when using the resin test. Using these characteristics of the receptor, we purified the receptor to 1220 pmol T3-binding capacity/mg protein with a final yield of 14.6 micrograms/4 kg rat liver. PMID- 2926299 TI - Formation of 4-oestrene-3,17-dione (19-norandrostenedione) by porcine granulosa cells in vitro is inhibited by the aromatase inhibitor 4-hydroxyandrostenedione and the cytochrome P-450 inhibitors aminoglutethimide phosphate and ketoconazole. AB - The origin and biosynthesis of 4-oestrene-3,17-dione (19-norandrostenedione), a major steroid in porcine ovarian follicular fluid, was investigated by culturing granulosa cells from 4-6 mm follicles of prepubertal gilts with radiolabelled androstenedione and 19-hydroxyandrostenedione. Steroid metabolites were purified by solvent extraction and lipophilic column chromatography, and analysed by C18 reverse-phase high-performance liquid chromatography. 19-Hydroxyandrostenedione, 19-norandrostenedione and oestradiol-17 beta were obtained as major metabolites from androstenedione, while 19-norandrostenedione and oestradiol-17 beta were the major products from 19-hydroxyandrostenedione. Serum alone or serum plus FSH significantly enhanced formation of 19-norandrostenedione and oestradiol-17 beta from each substrate, compared with controls. Micromolar concentrations (1 mumol/l) of 4-hydroxyandrostenedione, an aromatase inhibitor, significantly reduced formation of 19-norandrostenedione and oestradiol-17 beta by granulosa cells cultured with serum and FSH. Formation of 19-norandrostenedione and oestradiol-17 beta from androstenedione and 19-hydroxyandrostenedione was also significantly inhibited by aminoglutethimide phosphate, a cytochrome P-450 inhibitor known to block the conversion of androstenedione to oestrogens. Ketoconazole, an inhibitor of the cytochrome P-450 dependent 17,20-lysase, blocked formation of 19-norandrostenedione and oestradiol-17 beta only at millimolar concentrations. These results suggest that 19-norsteroid and oestrogen formation from C19 aromatizable androgens may share a common or overlapping pathway, and imply that 19-norsteroid and oestrogen synthesis is mediated by cytochrome P-450 dependent enzymes. PMID- 2926300 TI - Role of the adrenal cortex in chronic stress-induced inhibition of prolactin secretion in male rats. AB - The response of prolactin to chronic stress in intact, adrenalectomized and adrenomedullectomized male rats was studied. Immobilization stress in intact animals induced a significant increase in plasma concentrations of prolactin after 20 and 45 min and a significant decrease when the rats were submitted to chronic restraint (6 h daily for 4 days). Five weeks after adrenomedullectomy, plasma prolactin and corticosterone responses to chronic stress were not modified. In contrast, the inhibitory effect of chronic stress on prolactin secretion was totally suppressed by adrenalectomy. When treated with dexamethasone during the 4 days of restraint, adrenalectomized stressed rats showed similar plasma concentrations of prolactin to the intact stressed rats. These data indicate that the adrenal cortex is able to play an inhibitory role on prolactin secretion during stress only through a prolonged release of glucocorticoids. PMID- 2926301 TI - Effects of neonatal androgenization on growth and carcass composition in female mice. AB - Sixty female mice were injected neonatally with testosterone propionate. This led to an increase in body weight at 56 days (P less than 0.01) and a reduction in carcass fat (P less than 0.005). Food conversion ratio from 28 to 49 days was lower in the treated group than in the controls (P less than 0.01). The data indicate that treated females can reach values similar to those of males. Histological studies revealed a lack of luteal tissue in treated females at 56 days. This effect might be due to a modification in the nervous control of ovarian activity. Growth hormone secretion was higher in treated females than in controls (P less than 0.05). These results suggest that androgenization of females to achieve the performance characteristics of intact males could have important implications in meat production. PMID- 2926302 TI - Age-related variation in circadian rhythms of mitosis in the adrenal cortex of the male rat. AB - Using a metaphase arrest technique, mitotic activity was quantified in the adrenal cortex over a 24-h period in 14-day-old male Sprague-Dawley rats before functional rhythmicity of the hypothalamic pituitary-adrenal (HPA) axis is established, and after its onset, in 6- to 7-week-old rats. At all times, proliferative activity was greater in the younger animals, as previously reported. A significant circadian rhythm was identified in both groups, but the timing of the peak differed, lying between 17.00 and 21.00 h at 14 days and 11.00 and 15.00 h at 6-7 weeks. These results raise the possibility that functional rhythmicity of the HPA axis may alter an inherent proliferative rhythm. PMID- 2926303 TI - A dual role of growth hormone as a feminizing and masculinizing factor in the control of sex-specific cytochrome P-450 isozymes in rat liver. AB - The effects of GH on the major constitutive sex-specific forms of cytochrome P 450 (P-45015 beta and P-45016 alpha) were studied in hypophysectomized rats at the mRNA level. Time-course experiments were performed with or without simultaneous treatment with thyroxine and cortisol. Intermittent administration of GH, mimicking the male secretory pattern, caused complete masculinization of the male specific P-45016 alpha at a pretranslational level in the absence and presence of thyroxine and cortisol. When GH was administered continuously, mimicking the female secretory pattern, the female specific P-45015 beta was induced, an effect that was dramatically potentiated by simultaneous treatment with thyroxine and cortisol. A synergistic effect of thyroxine and cortisol at a pretranslational level was demonstrated, although the major potentiating effect could be attributed to thyroxine. Thus it was concluded that GH, depending on its secretory pattern is the sole masculinizing factor for cytochrome P-450, and that it is also a feminizing factor, although this activity requires the synergistic action of thyroid hormones and glucocorticoids to reach its full effect. PMID- 2926304 TI - Steroid concentrations in rat corpora lutea isolated during the oestrous cycle and pseudopregnancy: effect of induction of ovulation at dioestrus. AB - Corpora lutea could be identified under the dissection microscope up to 7 days after formation. They were isolated during the oestrous cycle and pseudopregnancy and the progesterone and 20 alpha-OH-progesterone contents were compared with serum values of these steroids. The pattern of progesterone in serum resembled that found in the corpora lutea. However, the pattern of 20 alpha-OH-progesterone concentrations in serum and corpora lutea were different. While 20 alpha-OH progesterone concentrations in the corpora lutea showed large variations during the cycle, changes in serum concentrations of 20 alpha-OH-progesterone were relatively small. Measurement of hormone concentrations in isolated corpora lutea is therefore a sensitive method for studying corpus luteum activity. To study whether corpora lutea derived after ovulation of immature follicles showed deficient luteal activity, rats at dioestrus (2 days before pro-oestrus) were induced to ovulate by the injection of 10 IU human chorionic gonadotrophin (hCG) and subsequent luteal activity was studied by measuring hormone concentrations in the corpora lutea on day 5 of pseudopregnancy. Concentrations of progesterone, but not of 20 alpha-OH-progesterone, in corpora lutea derived from follicles induced to ovulate at dioestrus-day 1 were significantly lower than those in corpora lutea derived from follicles induced to ovulate at proestrus. This difference was observed not only when pseudopregnancy was induced by cervical stimulation but also when it was induced by implantation of a pituitary gland under the kidney capsule. However, in the latter case, corpora lutea already present on the day of hCG injection also became activated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2926305 TI - Circulating reproductive hormones and hypothalamic oestradiol and progestin receptors in infertile Zucker rats. AB - Plasma concentrations of LH, FSH, prolactin and progesterone were measured during the oestrous cycle in obese (fa/fa) and non obese (Fa/?) Zucker rats. In obese rats the mid-afternoon surge of LH during prooestrus was reduced compared with that in non-obese rats (P less than 0.05), and the maximum concentrations of FSH and prolactin declined more slowly during oestrus. Progesterone concentrations were higher during most of the oestrous cycle in obese rats. Oestradiol and progestin receptors were measured in the hypothalamus of female Zucker rats. Lower concentrations of oestradiol receptors were found in the preoptic area of obese rats (P less than 0.05). Concentrations of oestradiol receptors in the medial basal hypothalamus were also lower in obese rats, though the difference was not statistically significant. Concentrations of progestin receptors were similar in both phenotypes in the preoptic area and media basal hypothalamus. It seems likely that the abnormalities in reproductive hormones and oestradiol receptors contribute to the infertility of obese female Zucker rats. The underlying mechanism has still to be determined. PMID- 2926306 TI - The effect of a 72-h fast on plasma levels of pituitary, adrenal, thyroid, pancreatic and gastrointestinal hormones in healthy men and women. AB - Seventeen human subjects fasted without electrolyte replacement for 3 days and hormone levels were measured before, during and after the fast. Immediate consequences of the fasting state in healthy human subjects include a marked increase in plasma cortisol. ACTH, beta-endorphin, beta-lipotrophic hormone, adrenaline, noradrenaline and dopamine. Levels of all these hormones were much greater on the first morning of the fast than in the post-prandial state, even though the plasma glucose level was no lower than that observed on the morning before the fast began. A clear fall in TSH and tri-iodothyronine (T3) levels was observed, but thyroxine levels did not change significantly. Insulin levels fell whereas proinsulin levels did not fall during the fast, though they did rise markedly upon re-feeding. An increase in GH levels was particularly apparent in male subjects, but was also seen in females when evening samples were compared. Pancreatic glucagon showed a modest rise during the fast, but fell again on refeeding; total glucagon also rose as the fast proceeded, but increased markedly upon re-feeding. Levels of gastrin and peptide YY remained low during the fast. Plasma electrolyte levels were unchanged. The following were closely correlated: cortisol with ACTH, T3 with log10 TSH, dopamine with noradrenaline, and (negatively, during the fast) pancreatic glucagon with glucose. PMID- 2926307 TI - Molecular endocrinology: a welcome extension to, but not a replacement for, endocrinology. PMID- 2926308 TI - Prenatal androgenization selectively modifies some responses to oestrogen in the prepubertal rat uterus. AB - Exposure of fetuses to some hormonally active agents may imprint permanent changes on the action of related hormones. These changes can be detected in adulthood as a modification of the degree of responsiveness to hormone action. The present study describes the effect of prenatal androgenization on the various responses to oestrogen in different types of cells in the uterus of prepubertal rats. Prenatal androgenization completely abolishes oestrogen-induced hypertrophy of uterine luminal and glandular epithelium, while it does not interfere with hypertrophy of circular myometrium and potentiates uterine eosinophilia and oedema. This dissociation between the various responses to oestrogen suggests that prenatal androgenization does not equally affect all uterine cell types. PMID- 2926310 TI - High-density lipoproteins (HDL) stimulate placental lactogen secretion in pregnant ewes: further evidence for a role of HDL in placental lactogen secretion during pregnancy. AB - Previous studies from our laboratory showed that high-density lipoproteins (HDL) stimulate the release of human placental lactogen (PL) from cultured trophoblast cells from normal pregnant women. To determine whether HDL stimulates PL secretion in vivo, ovine HDL was infused over 2-5 min into 11 pregnant ewes (22 separate experiments) at 86-130 days of gestation via an indwelling catheter into the maternal jugular vein. The HDL, freshly prepared from the plasma of pregnant ewes by differential flotation ultracentrifugation, was greater than 99% purified as judged by SDS-PAGE. Plasma samples were obtained from the ewes before and at 0.5-h intervals for 6 h following the infusions and were assayed for PL by a specific homologous radioimmunoassay. The maternal infusion of HDL at doses of 302-784 mg (5.3-13.8 mg/kg body weight) stimulated significant increases in maternal plasma PL concentrations in six out of eight experiments (six ewes), and the infusion of 108-264 mg (1.9-4.6 mg/kg) stimulated plasma PL concentrations in two out of six experiments. In contrast, HDL at doses less than 100 mg were without effect in eight experiments. The response to the HDL infusions was characterized by a sustained increase in plasma PL concentrations beginning 1.5 2.5 h after the infusions, reaching a maximum 274.2 +/- 21.9% of the baseline value (P less than 0.001). In contrast, the maternal infusion of lipoprotein-free plasma proteins or saline had no effect on maternal plasma PL concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2926309 TI - A monoclonal antibody to lactogenic receptors from female rat liver. AB - Affinity-purified lactogenic receptors from female rat liver microsomal membranes were used to raise antibodies in female Balb/c mice. Mouse spleen and myeloma cells were fused and hybridoma-derived monoclonal antibodies (Mabs) were produced by in-vitro cell culture. Mab from a selected clone was sequentially purified by chromatography on a thiophilic gel and on agarose-bound protein A. The Mab was found to be of IgG1 subclass and of kappa type. The Mab recognized membrane-bound and solubilized (by the detergent heptaoxyethylene lauryl ether; G3707) receptors as well as receptors purified by affinity chromatography and subsequent sodium dodecyl sulphate (SDS) electrophoresis from female rat liver. The Mab bound to receptors from several other female rat tissues, such as ovary, kidney and adrenal, whereas there was no binding to liver receptors from cow and rabbit. Displacement experiments showed that the Mab was specific for a lactogenic type of receptor, in agreement with the finding that the Mab did not recognize receptors from male rat liver. The Mab also bound to cytoplasmic receptors (present in the supernatant after centrifugation at 100,000 g) from female rat liver, suggesting a structural similarity between the cytoplasmic and the microsomal receptors. Analysis of purified receptors by SDS electrophoresis and subsequent Western blot with 125I-labelled Mab as a probe showed one band corresponding to an Mr of 45,500 +/- 2500 (n = 5). The same band was obtained with 125I-labelled human GH, showing that the Mab binds to the unit which accommodates the hormone-binding site.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2926311 TI - An enzyme-linked immunosorbent assay to study human relaxin in human pregnancy and in pregnant rhesus monkeys. AB - A sensitive and specific double-antibody enzyme-linked immunoassay, using a synthetic analogue of human relaxin for standard and immunogen, was developed for the measurement of human relaxin (hRLX) in serum and plasma. No cross-reactivity was observed for human insulin, human insulin-like growth factor-I, hGH, human chorionic gonadotropin, hFSH, hLH or human prolactin. The assay was used to monitor RLX concentrations in samples from men, non-pregnant and pregnant women, and in pregnant rhesus monkeys infused with hRLX. RLX was not detected in serum from men nor from non-pregnant women, while a concentration of 600 ng/l was measured in pooled sera from two pregnant women (pregnancies achieved by in-vitro fertilization). Immunoreactive RLX (1.1 micrograms/g) was found in human corpora lutea taken from ectopic pregnancies at 7 weeks. In an experiment with a pregnant rhesus monkey infused with human RLX analogue, less than 1.5% of the maternal concentration was measured in the fetal circulation. Even though preliminary, these data suggest a low level of transfer of human analogue relaxin across the placenta in a rhesus monkey. Further studies of the physiology of RLX in human pregnancy will be facilitated by the availability of this immunoassay. PMID- 2926312 TI - Maternal pinealectomy abolishes the diurnal rhythm in plasma melatonin concentrations in the fetal sheep and pregnant ewe during late gestation. AB - We have investigated the effect of pinealectomy of ewes in pregnancy on the presence of the diurnal rhythm in fetal and maternal plasma concentrations of melatonin. Six ewes were pinealectomized between 104 and 118 days of gestation. Fetal and maternal blood samples were collected during 24-h periods between 125 and 140 days of gestation in the pinealectomized ewes and in an intact control (n = 4). There was a significant diurnal rhythm in both fetal and maternal plasma concentrations of melatonin in the control group. In this group, the fetal and maternal plasma melatonin concentrations were significantly higher in the dark (128.4 +/- 6.2 and 192.2 +/- 10.7 pmol/l respectively) than in the light (46.2 +/ 4.2 and 25.8 +/- 2.1 pmol/l respectively). However there was no diurnal rhythm in either the fetal or maternal plasma melatonin concentrations in the pinealectomized group between 125 and 140 days of gestation. In contrast to the control animals, there was also no light-dark difference in the fetal or maternal plasma melatonin concentrations in four pinealectomized animals sampled frequently in the 3-7 days preceding delivery (mean length of gestation 146.5 days). However, in the pinealectomized sheep there was a gradual increase in the combined light-dark fetal plasma melatonin concentrations during late gestation from 27.9 +/- 2.8 pmol/l (at 15-20 days before delivery) to 95.2 +/- 14.1 pmol/l on the day of delivery. We have therefore demonstrated that the maternal pineal is the major source of the diurnal rhythm in maternal and fetal plasma melatonin concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2926313 TI - Hormonal dependence of the metrial gland: further studies on oestradiol and progesterone receptor levels in the rat. AB - The main objective of the present study was to analyse the hormonal dependence of the metrial gland formed in pseudopregnant animals following massive decidualization. On day 13 of pseudopregnancy (when the metrial gland reaches its maximal development) animals were ovariectomized and given s.c. implants of oestradiol and/or progesterone. A new implant technique for oestradiol delivery is described which provides circulating concentrations of oestradiol in the physiological range. In addition, we extended our previous work concerning oestradiol receptor and progesterone receptor concentrations in the metrial gland of pseudopregnant rats. The low oestradiol receptor concentration which we previously reported up to day 17 was maintained until the end of pseudopregnancy (day 21-1.5 fmol/micrograms DNA), whereas the progesterone receptor concentration remained raised (congruent to 3.5 fmol/micrograms DNA) from day 13 to day 19 and then decreased on day 21. The correlation of metrial gland weight and kinetics of the tissue oestradiol and progesterone receptors contents with the circulating oestradiol and progesterone concentrations lead to the following conclusions. First, the maintenance of the metrial gland is strictly progesterone-dependent. It is unlike the deciduoma which regresses spontaneously, even in the presence of progesterone. Secondly, the production of oestradiol receptor, but not of progesterone receptor, appears to be repressed in the metrial gland under the influence of progesterone. Thus, the tissue retains its ability to respond to progesterone because of a high concentration of progesterone receptor. It is difficult to attribute this high tissue progesterone receptor concentration to oestradiol stimulation since, even at low levels, oestradiol induces tissue regression. We suggest that the high progesterone receptor concentration could be due to constitutive (basal) progesterone receptor production. PMID- 2926314 TI - Effects of ethanol and inhibitors of its metabolism on the circulating levels of Met-enkephalin in greyhounds. AB - The mechanisms involved in the release of Met-enkephalin-like immunoreactivity (MLI) into the circulation following oral administration of ethanol and chlorpropamide were investigated in dogs. The origin of plasma MLI and the sites where it may be metabolized were also studied. Moreover, the molecular nature of circulating MLI was characterized. In conscious animals oral administration of ethanol (0.15 ml/kg) led to a significant (P less than 0.01) rise in plasma MLI concentrations in chlorpropamide-pretreated animals from a basal level of 43 +/- 6 (mean +/- S.E.M.) to a peak of 66 +/- 8 ng/l. Similar rises in MLI concentrations were observed following administration of ethanol with disulfiram and ethanol with chlorpropamide and captopril. In contrast, the administration of ethanol alone or ethanol with 4-methylpyrazole resulted in a decrease in plasma MLI concentrations. Comparisons of two different doses of i.v. acetaldehyde, the first metabolite of ethanol, showed that plasma MLI concentrations rose significantly (P less than 0.05) only after the larger dose (8 mg/kg), rising from 45 +/- 7 to 81 +/- 18 ng/l. These results suggest that acetaldehyde is the active component in the chlorpropamide + ethanol-induced MLI secretion. Plasma MLI was also measured following acetaldehyde infusion in adrenalectomized dogs with and without hexamethonium treatment. Acute bilateral adrenalectomy resulted in a decrease (P less than 0.05) in plasma MLI concentrations, but the levels remained detectable. Moreover, subsequent acetaldehyde infusion led to rises in plasma MLI similar to those observed in animals with intact adrenals. These MLI responses were not altered by the concurrent i.v. administration of hexamethonium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2926315 TI - Expression of human or bovine growth hormone gene with a mouse metallothionein-1 promoter in transgenic swine alters the secretion of porcine growth hormone and insulin-like growth factor-I. AB - Endocrine profiles were examined in swine that had integrated and expressed a fusion gene consisting of mouse metallothionein-1 (MT) promoter fused to either a human (h) or bovine (b) GH structural gene. Eleven of 18 pigs that had integrated MT-hGH and eight of nine pigs that had integrated MT-bGH expressed the genes. The level of expression varied widely among pigs (14-4551 micrograms/l for MT-hGH and 23-1578 micrograms/l for MT-bGH). The level of expression varied over time within each pig with no general pattern. Concentrations of porcine GH (pGH) were lower in MT-hGH pigs that expressed the gene than in non-expressors or in littermate controls. Insulin-like growth factor-I (IGF-I) concentrations increased with age in all pigs and were raised threefold in pigs expressing either the MT-hGH or MT bGH genes. Measurement of the foreign GH in samples taken at 15-min intervals failed to reveal any short-term fluctuations in concentration. Administration of hGH releasing factor (GRF) to pigs expressing MT-bGH resulted in attenuated release of pGH compared with that of contemporary controls. Concentrations of bGH did not change after GRF injection. Human and bovine GH expressed in transgenic pigs appear to be biologically active in that they induce IGF-I and suppress endogenous pGH secretion. The failure to find short-term fluctuations and the lack of response to GRF injections are consistent with a non-pituitary and non GRF regulatable site of production. PMID- 2926317 TI - Ionic and total calcium levels in the blood of the European eel (Anguilla anguilla): effects of stanniectomy and hypocalcin replacement therapy. AB - Removal of the corpuscles of Stannius (STX) in the freshwater European eel causes a marked increase in the concentrations of blood ionic calcium and protein-bound calcium. The hypercalcaemia peaks 20 days after STX and lasts at least another 20 days. In stanniectomized eels hypocalcin decreased both blood ionic and total calcium concentrations. The reduction of plasma total calcium concentration by hypocalcin is attributed to a reduction in blood ionic calcium concentration. We conclude that hypocalcin regulates blood ionic calcium levels in fish. PMID- 2926316 TI - Age-dependent changes in volume and haemoglobin content of erythrocytes in the carp (Cyprinus carpio L.). AB - Carp erythrocytes were fractionated by angle-head centrifugation which yielded fractions with a linear increase in density. Haematological examinations revealed that the heavier red blood cells of carp had greater volumes (MCV), more haemoglobin (MCH) and higher haemoglobin concentrations (MCHC) than light ones. The same experiments with human red cell fractions yielded a decrease in MCV, constant MCH and an increase in MCHC. Haemoglobin content in individual erythrocytes was also determined by scanning stage absorbance cytophotometry to establish the frequency distribution of the cellular haemoglobin contents. In carp, the distribution was symmetrical with the means increasing with density. No such change with cell density was found in human erythrocytes. Both carp and human erythrocytes incorporated [2-14C]glycine in vitro. After gel filtration, radioactivity was detected in carp, but not in human, haemoglobin fractions. 14C was found in all three haemoglobin fractions, obtained by isoelectric focusing, and was present in the haem and in the globin. [2-14C]glycine-labelled erythrocytes were reinjected into chronically cannulated carp and followed in vivo for several months. With time, the main peak of scintillation counts shifted from red cell fractions of low to high density. This is considered as evidence that density and age of red cells in carp are positively correlated and that erythrocytes can synthesize haemoglobin while circulating in the peripheral blood. PMID- 2926318 TI - Strontium is required for statolith development and thus normal swimming behaviour of hatchling cephalopods. AB - When cephalopod eggs were incubated in artificial sea water it was found that they sometimes resulted in hatchlings with defects of the statocyst suprastructure, leading to the severe behavioural defect of uncontrolled swimming. Experiments in defined media (seven basic salts mixed in deionized water) with seven species of cephalopods demonstrated clearly that there is 100% normal development of the aragonite statoliths when strontium levels were 8 mg l 1. Conversely, statoliths did not develop when strontium was absent. In cuttlefish, the growth of the cuttlebone was also affected adversely when strontium was absent. In mariculture production tanks, supplementing commercial artificial sea water with strontium to normal levels of 8 mg l-1 almost eliminated the occurrence of abnormal hatchlings. Circumstantial evidence indicates that there is a critical window in development during which strontium is required for normal development. The role of strontium in biomineralization during embryogenesis is unknown, but it appears to be important in the Mollusca. PMID- 2926319 TI - Efficiency of rat medial gastrocnemius muscle in contractions with and without an active prestretch. AB - The efficiency of positive work was measured for rat medial gastrocnemius muscle at 25 degrees C during repeated contractions. Six muscles were stimulated to perform concentric contractions preceded by an active prestretch (PS contractions) and six muscles made to give concentric contractions from an isometric state (PI contractions). Both lengthening and shortening of the muscles (distance: 6 mm) occurred at a constant velocity of 20 mm s-1 (1.5 fibre lengths s-1). Stimulation was started 150 ms prior to the onset of concentric contraction for both types of contraction. For the PS contractions this meant that the active state was developed during the last 2.4 mm of the lengthening. Energy consumption (calculated from high-energy phosphate consumption) appeared to be equal for both types of contraction, although positive work output was 39.4% higher in the PS contractions than in the PI contractions. The efficiency of positive work was 36.8 +/- 3.5% in the PS contractions and 26 +/- 2.0% in the PI contractions. In contrast to results of previous studies, the positive work done by the muscle in the PS contractions was much larger than the negative work done on the muscle during stretch owing to the applied stimulation protocol which was intended to simulate in vivo conditions during running. The efficiency of positive work in the PS contractions is too low to explain the efficiencies of 40-70% reported for human and animal running. PMID- 2926321 TI - No relationship between progressive muscle hyperaemia and temperature in exercising rats. AB - During prolonged submaximal exercise muscle blood flow has been shown to increase progressively in rats and miniature swine. This study was designed to test the hypothesis that the increases in muscle blood flow are associated with progressive elevations in body temperature in rats. Colonic temperature and muscle blood flow (determined using radioactive microspheres) were measured after 15, 30 and 45 min of exercise in rats exercising on a treadmill at 15 m min-1 on a 0 degree incline. Total hindlimb muscle blood flow increased from 79 +/- 8 ml min-1 100 g-1 at 15 min to 95 +/- 10 ml min-1 100 g-1 at 30 min (P less than 0.05). The greatest increases in blood flow occurred in the deep extensor muscles of the hindlimb. For example, in the red portion of the gastrocnemius muscle, blood flow increased from 197 +/- 15 ml min-1 100 g-1 at 15 min to 285 +/- 17 ml min-1 100 g-1 at 30 min (P less than 0.05). Colonic temperature, however, remained stable at 38.5 degrees C over this period. These data indicate that the progressive hyperaemia in muscle was unrelated to body temperature. PMID- 2926320 TI - Kappa-bungarotoxin blocks nicotinic transmission at an identified invertebrate central synapse. AB - A comparison was made between the effects of kappa-bungarotoxin and alpha bungarotoxin upon nicotinic cholinergic transmission at an identified synapse (the cereal afferent, giant interneurone 2 synapse) in the central nervous system of the cockroach (Periplaneta americana). kappa-Bungarotoxin, a snake venom kappa neurotoxin, completely blocked nicotinic unitary excitatory postsynaptic potentials (EPSPs) and evoked composite EPSPs when applied at a concentration of 1.0 x 10(-7) moll-1. No recovery was observed after a 2h wash in normal saline. kappa-Bungarotoxin produced a decrease in acetylcholine-induced nicotinic responses which paralleled decreases in nicotinic synaptic potentials and currents, indicating that kappa-bungarotoxin blocked postsynaptic nicotinic receptors. This blockade appeared to be specific as resting membrane potential, input resistance and the ability to elicit an action potential in response to direct stimulation of giant interneurone 2 were unchanged following prolonged toxin exposures. Samples of alpha-bungarotoxin which were free from kappa neurotoxin contamination were also found to be potent antagonists of cockroach neuronal nicotinic receptors. It is concluded that the cockroach receptor is the first reported example of a neuronal nicotinic receptor which is sensitive to blockade by both kappa-neurotoxins and alpha-neurotoxins. PMID- 2926322 TI - Elastase inhibitor. Characterization of the human elastase inhibitor molecule associated with monocytes, macrophages, and neutrophils. AB - A fast-acting inhibitor of serine elastase has been detected at high levels in human neutrophils, fresh monocytes, matured monocytes, and macrophages. The elastase inhibitor was isolated from large scale cultures of the monocyte-like cell line U937 by DNase chromatography, disulfide exchange, Phenyl-Sepharose, Red A-agarose, and DEAE HPLC chromatography with an average yield of 480 micrograms from 1.8 x 10(10) cells. The isolated polypeptide was verified as elastase inhibitor by its ability to (a) form a covalent complex with elastase; and (b) inhibit the elastinolytic activity of elastase. The purified elastase inhibitor molecule is unique, i.e., physiochemical and/or functional properties distinguish it from all other serine proteinase inhibitors. Treatment with iodoacetamide abrogates the ability of the molecule to form a complex with elastase, thereby providing evidence for the presence of an essential cysteine residue. Based on functional criteria, this elastase inhibitor has been grouped with the proteinase inhibitors of the serpin superfamily. The purified elastase inhibitor is a single polypeptide of Mr approximately 42,000. The NH2 terminus appears to be blocked. Compositional analyses indicates five cysteine residues per molecule of approximately 360 amino acid residues. Negligible levels of carbohydrate were detected on gas-liquid chromatography. This finding and the insensitivity of the molecule to peptide N-glycosidase F treatment strongly indicate that the elastase inhibitor is a nonglycosylated protein. PMID- 2926323 TI - Chlamydial disease pathogenesis. Ocular hypersensitivity elicited by a genus specific 57-kD protein. AB - Recurrent or persistent infections with Chlamydia trachomatis are thought to provide the antigenic stimulus for the chronic inflammation associated with blinding trachoma. We used the guinea pig model of inclusion conjunctivitis to identify chlamydial antigens that may be involved in this deleterious immune response. We purified from chlamydial elementary bodies a genus-specific 57-kD protein that elicited an ocular hypersensitivity response when placed topically onto the conjunctiva of ocular immune guinea pigs. This response was characterized by a predominantly mononuclear macrophage and lymphocyte cellular infiltrate of the submucosal epithelium. The clinical and histological findings were consistent with those of a delayed hypersensitivity response. These data demonstrated that the 57-kD chlamydial protein was a potent stimulator of ocular delayed hypersensitivity. Our findings may be critical to understanding the pathogenesis of the debilitating chlamydial diseases associated with chronic inflammation, such as trachoma and many urogenital syndromes. PMID- 2926324 TI - Vaccination with the major secretory protein of Legionella pneumophila induces cell-mediated and protective immunity in a guinea pig model of Legionnaires' disease. AB - We have examined the capacity of the major secretory protein (MSP) of Legionella pneumophila to induce humoral, cell-mediated, and protective immunity in a guinea pig model of Legionnaires' disease. MSP was purified to homogeneity by ammonium sulfate precipitation, molecular sieve chromatography, and ion-exchange chromatography. The purified MSP was nonlethal and nontoxic to guinea pigs upon subcutaneous administration. Guinea pigs immunized with a sublethal dose of aerosolized L. pneumophila or a subcutaneous dose of MSP developed a strong cell mediated immune response to MSP. Such guinea pigs exhibited marked splenic lymphocyte proliferation and cutaneous delayed-type hypersensitivity to MSP in comparison with control animals. Guinea pigs immunized with MSP also developed a strong humoral immune response to MSP, as assayed by an ELISA. The median reciprocal antibody titer was 362 (range 45 to greater than 2,048) for immunized animals compared with less than 8 for controls. In contrast, guinea pigs immunized with a sublethal dose of L. pneumophila failed to develop anti-MSP antibody. Guinea pigs immunized with MSP and then challenged with a lethal aerosol dose of L. pneumophila exhibited highly significant protective immunity in each of five consecutive experiments. MSP induced protective immunity in dose dependent fashion (40 greater than 10 greater than 2.5 greater than 0.6 micrograms MSP); vaccination with two doses of as little as 2.5 micrograms MSP induced significant protective immunity (p = 0.01, Fisher's Exact Test, two tailed). Altogether, 21 (81%) of 26 animals immunized with 40 micrograms MSP survived challenge compared with 0 (0%) of 26 sham-immunized control animals (p = 7 x 10(-10), Fisher's Exact Test, two-tailed). MSP-immunized but not control guinea pigs were able to limit L. pneumophila multiplication in their lungs. This study demonstrates that (a) guinea pigs sublethally infected with L. pneumophila develop a strong cell-mediated immune response to MSP; (b) guinea pigs immunized with MSP develop a strong humoral and cell-mediated immune response to MSP; (c) guinea pigs immunized with MSP develop a very high level of protective immunity to lethal aerosol challenge with L. pneumophila; and (d) MSP-immunized animals are able to limit L. pneumophila multiplication in their lungs. MSP, an extracellular protein of an intracellular pathogen, has potential as a vaccine for the prevention of Legionnaires' disease. Secretory molecules of other intracellular pathogens may also have vaccine potential. PMID- 2926326 TI - Interferon alpha associated with systemic lupus erythematosus is not intrinsically acid labile. AB - The physicochemical properties of apparently acid-labile IFN-alpha from patients with SLE have been studied. The antigenicity, apparent molecular size, and isoelectric point of SLE IFN-alpha are indistinguishable from those of conventional, previously characterized, acid-stable subspecies of IFN-alpha. However, after partial purification by anion-exchange chromatography, SLE IFN alpha no longer exhibits acid lability, suggesting that other plasma factor(s) are responsible for the acid lability of SLE IFN-alpha. Addition of SLE plasma, but not normal plasma, to conventional acid-stable IFN-alpha renders the exogenous IFN-alpha acid labile. Preliminary results demonstrate that an acid dependent IFN-inactivating activity can be partially purified from SLE plasma by anion-exchange chromatography. PMID- 2926325 TI - A population of murine hematopoietic progenitors expresses an endogenous retroviral gp70 linked to the Rmcf gene and associated with resistance to erythroleukemia. AB - Multiple copies of retroviral sequences are stably integrated in the genomes of many higher organisms, and are thus transmitted vertically to offspring via the germline (1). Most of these heritable viral genes are not expressed, and expression, when observed, is commonly limited to envelope (env) genes as demonstrated by the presence of cell surface and serum envelope glycoprotein (gp70) in mice. Studies of the mouse have shown that certain tissues such as the reproductive tract and lymphoid organs are common sites for the expression of endogenous env genes, suggesting that the transcription of at least some endogenous sequences is tissue specific. The transcription of endogenous viral genes is regulated by both cis and trans mechanisms (2-5) and their expression can be temporally linked to differentiation and development (6-8). The consequences to the host of endogenous retroviral genes are varied. At one extreme, expression of endogenous virus can result in the development of leukemia and death. Another potentially detrimental effect is that of insertional mutagenesis, seen when the integration of retroviral sequences interrupts the functioning of a cellular gene (9, 10). However, it is now clear that expression of endogenous retroviral genes may also have a beneficial effect for the host: namely, mediating resistance to retroviral leukemias as has been demonstrated for the Fv-4 gene in mice (11) and some ea loci in chickens (12). This form of resistance is due to the blockage of cellular viral receptors by the expression of envelope glycoprotein on the cell surface. The Rmcf locus of the mouse is another resistance gene that may exert its effect by the expression of an endogenous env gene. A summary of our current state of knowledge concerning the Rmcf gene is shown in Table I. The Rmcf gene was originally described when it was observed that fibroblast cell cultures derived from certain strains of mice restricted the replication of recombinant mink cell focus-forming(MCF)1 viruses (13). As detailed in Table I, DBA/2 mice are the prototypic strain exhibiting the Rmcf resistance (Rmcf(r)) phenotype. Cell cultures from other strains, such as C57BL/6 and IRW, are permissive for MCF viral replication and are termed Rmcf sensitive (Rmcf(s)). Previously, we described two allelic forms of an endogenous env gene, whose expression is linked to the Rmcf gene (14). Cell cultures from Rmcf(r) mice express gp70 related to that of MCF viruses, whereas cultures derived from Rmcf(s) mice either express no gp70 (IRW) or express an endogenous xenotropic gp70 (C57BL/6). These two gp70 alleles are detectable by type-specific mAbs. PMID- 2926327 TI - Developmental and tissue-specific expression of nuclear proteins that bind the regulatory element of the major histocompatibility complex class I gene. AB - Expression of MHC class I genes varies according to developmental stage and type of tissues. To study the basis of class I gene regulation in tissues in vivo, we examined binding of nuclear proteins to the conserved cis sequence of the murine H-2 gene, class I regulatory element (CRE), which contains two independent factor binding sites, region I and region II. In gel mobility shift analyses we found that extracts from adult tissues that express class I genes, such as spleen and liver, had binding activity to region I. In contrast, extracts from brain, which does not express class I genes, did not show region I binding activity. In addition, fetal tissues that express class I gene at very low levels, also did not reveal region I binding activity. Binding activity to region I became detectable during the neonatal period when class I gene expression sharply increases. Most of these tissues showed binding activity to region II, irrespective of class I gene expression. Although region II contained a sequence similar to the AP-1 recognition site, AP-1 was not responsible for the region II binding activity detected in this work. These results illustrate a correlation between region I binding activity and developmental and tissue-specific expression of MHC class I genes. The CRE exerts an enhancer-like activity in cultured fibroblasts. We evaluated the significance of each factor binding to CRE. Single 2-bp mutations were introduced into the CRE by site-directed mutagenesis and the ability of each mutant to elicit the enhancer activity was tested in transient CAT assays. A mutation that eliminated region I protein binding greatly impaired enhancer activity. A mutation that eliminated region II binding also caused a lesser but measurable effect. We conclude that region I and region II are both capable of enhancing transcription of the class I gene. These results indicate that in vivo regulation of MHC class I gene expression is mediated by binding of trans-acting factors to the CRE. PMID- 2926328 TI - Mouse macrophage hemagglutinin (sheep erythrocyte receptor) with specificity for sialylated glycoconjugates characterized by a monoclonal antibody. AB - An inhibitory rat mAb, SER-4, has been raised to the mouse macrophage (M phi) restricted hemagglutinin, sheep erythrocyte receptor (SER), which binds unopsonized sheep erythrocytes through recognition of sialylated glycoconjugates. This receptor was originally defined on mouse resident bone marrow M phi where it was implicated in adhesive interactions of these cells with proliferating hematopoietic cells. In the present study using mouse serum-induced thioglycollate-elicited peritoneal M phi (TPM) as a model system for SER expression, mAb SER-4 IgG2a completely blocked rosette formation at 1 microgram/ml. The inhibition was likely to be via steric hindrance rather than through a direct interaction with the putative sialic acid binding site of SER because F(ab')2 and Fab fragments of mAb SER-4 gave a maximum inhibition of 50 60% and 0% respectively, despite binding effectively to the SER-4 antigen (Ag). Immunoprecipitation and Western blotting experiments with cultured M phi or tissue extracts demonstrated that the Ag recognized by SER-4 mAb is a single chain molecule with an apparent Mr by SDS-PAGE of 185 x 10(3) (reduced) or 170 x 10(3) (non-reduced) and is distinct from members of the leukocyte common Ag family. Expression of SER and SER-4 Ag in culture were closely correlated and depended on the presence of mouse serum for optimal induction. Further evidence that the SER-4 Ag is functionally equivalent to SER was provided by immunocytochemistry in which the overall pattern of staining in tissues was consistent with previous rosetting experiments. In the bone marrow, expression of the SER-4 Ag was restricted to the resident bone marrow M phi population with no expression on monocytes. High expression was also observed on stromal M phi within the subcapsular sinus and medullary cords in lymph nodes and on marginal metallophils in the spleen. These results therefore confirm that SER is a novel M phi-restricted receptor whose distribution and properties indicate a role in cellular interactions in hematopoietic and lymphoid tissues. PMID- 2926329 TI - Purification and amino acid analysis of two human glioma-derived monocyte chemoattractants. AB - Two chemoattractants for human monocytes were purified to apparent homogeneity from the culture supernatant of a glioma cell line (U-105MG) by sequential chromatography on Orange A-Sepharose, an HPLC cation exchanger, and a reverse phase HPLC column. On SDS-PAGE gels under reducing or nonreducing conditions, the molecular masses of the two peptides glioma-derived chemotactic factor 1 and 2 were 15 and 13 kD, respectively. Amino acid composition of these molecules was almost identical, and differed from other cytokines that have been reported. The NH2 terminus of each peptide was apparently blocked. When tested for chemotactic efficacy, the peptides attracted approximately 30% of the monocytes added to chemotaxis chambers, at the optimal concentration of 10(-9) M. Potency and efficacy were comparable with that of FMLP, which is often used as a reference attractant. The activity was chemotactic rather than chemokinetic. In contrast to their interaction with human monocytes, the pure peptides did not attract neutrophils. These pure tumor-derived chemoattractants can now be compared with attractants produced by normal cells and evaluated for their biological significance in human neoplastic disease. PMID- 2926331 TI - Purification and characterization of a novel monocyte chemotactic and activating factor produced by a human myelomonocytic cell line. AB - A novel basic heparin-binding monocyte chemotactic factor (MCF) was purified to homogeneity from the conditioned media of human myelomonocytic cell line THP-1 based on its in vitro monocyte chemotactic activity. The purified MCF was homogenous and estimated to be 15 kD on SDS-PAGE. Purified MCF stimulated normal human monocytes to be growth inhibitory in vitro at 2-3 d for several human tumor cell lines. This represents the first report of the identification and purification of a chemoattractant cytokine that also activates monocytes but is distinct from interferons and other known cytokines. PMID- 2926330 TI - An L-arginine-dependent mechanism mediates Kupffer cell inhibition of hepatocyte protein synthesis in vitro. AB - The hepatic failure associated with severe sepsis is characterized by specific, progressive, and often irreversible defects in hepatocellular metabolism (1). Although the etiologic microbe can often be identified, the direct causes and mechanisms of the hepatocellular dysfunction are poorly understood. We have hypothesized that Kupffer cells (KC), which interact with ambient septic stimuli, respond by providing signals to adjacent hepatocytes (HC) in sepsis . Furthermore, we have provided evidence (2, 3) that KC activated by LPS from Gram negative bacteria can induce profound changes in the function of neighboring HC in coculture. In our model, coculture of either KC (2) or peritoneal macrophages (Mphi)(3) with HC normally promotes HC protein synthesis ([(3)H]leucine incorporation). The addition of LPS or killed Escherichia colt' to such cocultures induces a profound decrease in HC protein synthesis, as well as qualitative changes ([(35)S]methionine, SDS-gel electrophoresis) in protein synthesis without inducing HC death (2, 3) . In this report we show that the inhibition in protein synthesis is mediated via an L-arginine-dependent mechanism. The metabolism of L-arginine by activated Mphi to substances with cytostatic and even lethal effects on target cells is a relatively recent discovery. After the description by Stuehr and Marletta (4, 5) that LPS- triggered Mphi produced nitrite/nitrate (NO(2)(-)/NO(3)(-)), Hibbs et al. (6, 7) and Iyengar et al. (8) demonstrated that L-arginine was the substrate for the formation of both these nitrogen end products and citrulline. A role for the arginine-dependent mechanism in Mphi tumor cytotoxicity (6, 7) and microbiostatic activity (9) has been suggested. However, the in vivo functions of this novel Mphi mechanism have not yet been defined, but it is possible that there are both physiologic as well as pathologic roles. Our in vitro results raise the possibility that some metabolic responses to microbial invasion maybe partially mediated by the L-arginine-dependent mechanism. What other metabolic responses are affected and the possible pathologic consequences remain to be studied. PMID- 2926332 TI - Odd-item search in pigeons: display size and transfer effects. AB - Pigeons searched arrays of small forms displayed on computer monitors. On each trial, a single target form appeared together with two or more identical distractor forms. A set of six different forms was used in each of three experiments. All possible combinations of these forms, paired as target and distractor, appeared in each experimental session. Both the accuracy and speed of search increased with the number of distractors displayed. When both targets and distractors were new, accuracy was above chance only for the large (24 item) display, where transfer was highly significant. The experiments do not support the attribution to pigeons of a general "oddity concept." Rather, the results suggest that odd-item performance depends in part on a perceptual isolation of the target and in part on familiarity with target-distractor combinations. PMID- 2926333 TI - Timing light and tone signals in pigeons. AB - Pigeons' ability to time light and tone stimuli was examined in four experiments. In Experiment 1, two groups of pigeons were trained to discriminate between 2- and 8-s durations of lights or tones and then were transferred to reversal or nonreversal discriminations in the alternate modality. Pigeons learned the light discrimination faster than the tone discrimination and showed immediate positive intermodal transfer from tone to light but not from light to tone. In Experiments 2-4, the peak procedure was used to study birds' timing of 15- and 30-s fixed interval light and tone signals. Peak times on empty trials under baseline conditions closely approximated the length of fixed-interval signals. When pigeons were tested with time-outs and intermodal switches introduced midway through an empty trial, they tended to reset the timing mechanism and begin timing again from 0 s. With both estimation and production procedures, pigeons were less accurate when timing the tone stimuli than when timing the light stimuli. A comparison of these data with data from timing experiments with rats suggests several possible differences in timing processes between pigeons and rats. PMID- 2926334 TI - Preference for unpredictable food rewards occurs with high proportion of reinforced trials or alcohol if rewards are not delayed. AB - Organisms typically prefer situations where reward and nonreward are predictable rather than unpredictable. Although many theories can account for this result (e.g., information theory and delay-reduction theory), a recently developed mathematical model (DMOD) also predicts that subjects prefer the unpredictable reward situation under conditions that substantially decrease aversiveness of unpredictable nonreward (Daly & Daly, 1982). Because a high proportion of reinforced trials (lenient schedule) and alcohol injections decrease aversive conditioning, these variables were tested with rats in five E-maze experiments. A choice to one side of the maze resulted in a stimulus uncorrelated with reward outcome (unpredictable situation). A choice to the other side resulted in stimuli correlated with reward and nonreward (predictable situation). The stimuli were not visible until after the choice was made. A lenient reinforcement schedule resulted in preference for the unpredictable reward situation if rewards were not delayed. Alcohol resulted in preference for the unpredictable reward situation if a medium five-pellet reward was given. A lenient reinforcement schedule combined with an alcohol injection resulted in faster acquisition of the preference for the unpredictable reward situation than did a lenient schedule combined with a saline control injection. These results pose a major challenge to most theories, yet were predicted by DMOD. PMID- 2926335 TI - Influence of long-term sensitization on long-term habituation of the acoustic startle response in rats: central gray lesions, preexposure, and extinction. AB - The relation between long-term decrements of the acoustic startle response in rats and the development of freezing behavior during habituation training was examined. Freezing behavior developed over the initial trials of habituation training, and the rate of long-term response decrements was found to be inversely related to the development of freezing. Manipulations (neurological or behavioral) that either reduced the level of freezing or retarded its development promoted startle response decrements. In Experiment 1, rats receiving electrolytic lesions of the ventrolateral periaqueductal gray demonstrated both accelerated long-term startle response decrements and retarded development of freezing behavior. In Experiment 2, preexposure to the startle apparatus (i.e., latent inhibition) accelerated long-term startle decrements and inhibited development of freezing. In Experiment 3, exposure to the startle apparatus following initial habituation training (i.e., extinction) reduced both freezing behavior and startle response amplitudes. The results are discussed in terms of the influence of Pavlovian fear conditioning on long-term habituation of the acoustic startle response. PMID- 2926336 TI - Fetal heart variability and fetal well-being. PMID- 2926337 TI - Paradigms and family medicine. PMID- 2926338 TI - Sigmoidoscopy by family physicians. PMID- 2926339 TI - The relinquishing-adopting patient and the family physician. PMID- 2926340 TI - Obstetric risk assessment. PMID- 2926341 TI - A rational approach to cancer pain management. PMID- 2926342 TI - A correlation between serum cholesterol and glycosylated hemoglobin in nondiabetic humans. AB - The relationship of serum cholesterol and average blood glucose as glycosylated hemoglobin was investigated in 43 nondiabetic subjects. Glycosylated hemoglobin correlated strongly with total cholesterol (r = .63, P less than .001). A significant negative partial correlation (r = -.25, P = .05) was seen between high-density lipoprotein cholesterol and glycosylated hemoglobin if total cholesterol was held constant. This negative partial correlation was much stronger when the analysis was limited to subjects with total cholesterol greater than 5.20 mmol/L (200 mg/dL, r = -.51, P = .006). Subjects at high risk for atherosclerosis with total cholesterol greater than 7.25 mmol/L (280 mg/dL) have a glycosylated hemoglobin (6.32 percent) that is in the range of well-controlled diabetics. Subjects with moderately elevated cholesterol have moderately elevated glycosylated hemoglobin (5.92 percent) compared with normocholesterolemic subjects (5.53 percent). These results support the hypothesis that elevated blood glucose that is associated with hypercholesterolemia is responsible for some of the atherogenesis associated with high cholesterol levels. PMID- 2926344 TI - Present status of obstetrics in family practice and the effects of malpractice issues. AB - A survey of 800 active members of the American Academy of Family Physicians 1985 1987 membership directory was conducted for the purpose of determining the impact, over time, of malpractice issues upon the practice of obstetrics by family physicians. The survey response rate was 60.4 percent. Almost 20 percent of all respondents reported that they have never provided obstetric care of any type. Another 40 percent have provided obstetric care previously but have now discontinued this care, while the remaining 40 percent currently offer obstetric care to their patients. The proportion of respondents who discontinued the practice of obstetrics because of increased risk of malpractice litigation increased significantly over the years from 1947 to 1986 (P = .0084). The proportion of respondents who discontinued obstetric practice because of increased malpractice insurance costs also increased significantly from 1945 to 1986 (P = .0002). The proportion of those entering practice during the past five years who decided not to offer obstetric services because of malpractice risks was significantly greater than the proportion entering practice earlier (21.0 percent vs 2.0 percent, P = .0090). Although the current patterns of obstetric practice showed regional variation, the accelerating impact of malpractice risk and insurance cost on these patterns was similar throughout the nation. PMID- 2926343 TI - A comparison of two antismoking interventions among pregnant women in eleven private primary care practices. AB - Despite the dangers of smoking during pregnancy having been widely publicized, few studies have actually examined the effectiveness of antismoking interventions among pregnant women in the private primary care obstetric setting. A randomized experimental study involving 24 private physicians and 109 pregnant smokers was conducted comparing the American Lung Association's Because You Love Your Baby smoking intervention (ALA) to a standard-of-care protocol (non-ALA). The non-ALA protocol was based upon the smoking interventions that study physicians said they commonly used among pregnant women. Self-reported smoking rates were obtained by questionnaire at the first prenatal visit, at 32 to 36 weeks' gestation, and at the six-week postpartum visit. By the time of the first prenatal visit, both groups reduced by half the number of cigarettes smoked. By 32 to 36 weeks, the groups decreased the daily average by an additional 2.3 (ALA) and 1.8 (non-ALA) cigarettes, a nonsignificant difference between the groups. Fifteen (28 percent) of the ALA group compared with 9 (16 percent) of the non-ALA group reported quitting at the 32- to 36-week visit (P = .10). Only 9 percent of the ALA group and 10 percent of the non-ALA were nonsmokers at the postpartum visit. Pregnancy alone is a powerful motivator for women to decrease their smoking. Although the difference between the ALA and non-ALA protocols did not attain statistical significance, the percentage of those who quit was comparable to the results obtained in other controlled trials. The ALA Because You Love Your Baby protocol should be used until more effective methods are available. PMID- 2926345 TI - The Journal of Family Practice 1974-1988. Window to an evolving academic discipline. AB - This paper examines the spontaneous evolution of original work in family practice as published in The Journal of Family Practice over the 15-year period since it began publication in 1974. An analysis was carried out by principal content and type of paper for the last five years in a manner comparable to an earlier analysis of the journal's first ten years of publication. Trends that emerge from this reanalysis provide a window to observe the further development of family medicine as a scientific and academic discipline. The last five years have seen a marked increase in clinical content of papers (from approximately 60 to 80 percent of published papers) together with continued emphasis on health services subjects. There has been a concurrent sharp increase in research papers, continued strong representation of case studies, and some decrease in both reviews and methods papers. Descriptive research continues to predominate among research papers. Although experimental research still represents only 5 percent of published papers, this percentage has more than doubled over the last five years. The reanalysis also revealed a substantial decline in the proportion of educational papers, as other journals in the field have assumed the primary role for this content area. It appears that the manuscript supply represented by original work in the field is still limited and that there is at present adequate or even surplus journal capacity for publication of work carried out in family practice settings. The quality and type of work continue to mature consistent with the needs of family medicine as a scientific and academic discipline. PMID- 2926346 TI - Fine-needle breast aspiration biopsy. AB - Fine-needle aspiration biopsy of breast lesions is a safe, accurate, well tolerated procedure that can easily be done in the family physician's office. It has a specificity and positive predictive value of virtually 100 percent, a sensitivity of 53 to 99 percent (median of 89 percent), and a negative predictive value of 80 to 99 percent (median of 93 percent). It is limited by the nature of the lesion, which must be easily palpable, the physician's technical ability, and the availability of a reference cytopathologist. Complications are rare and usually very benign, such as local hematoma. With proper training and understanding of the procedure, many family physicians could easily introduce the procedure into their office practice. PMID- 2926347 TI - Workshop for teaching fundamentals of obstetric forceps. PMID- 2926348 TI - Hepatic adenoma and oral contraceptive use. PMID- 2926349 TI - First vs last name preferences of patients. PMID- 2926350 TI - Contraindications to live-viral immunization. PMID- 2926351 TI - Smoking cessation. PMID- 2926352 TI - Practice attrition and health plan changes. PMID- 2926353 TI - Uses of family information. PMID- 2926354 TI - Do amiloride and ouabain affect ammonia fluxes in perfused Carcinus gill epithelia? AB - The effects of inhibitors on the efflux of ammonia (from the basolateral to the apical side, Jb----a) were studied in preparation of isolated Carcinus gills immersed in dilute seawater (DSW) that was identical to the perfusion solution. Adding 10(-4) M amiloride to the solution bathing the gill preparations reduces the efflux of ammonia by 29% relative to the control value. Under experimental conditions, it appears that only about 1% of the amiloride-sensitive influx of Na+ (Ja----b) can be exchanged with NH4+ on an equimolar basis. The ammonium ion is apparently transported at the basolateral side by a carrier-mediated process. Kinetic analyses of the influx of ammonium ions revealed a Km of 36.99 microM and a maximum velocity (Vmax) equal to 19.6 mumol g-1.h-1. Basolaterally applied ouabain (5 x 10(-3) M) and NaCN (10(-3) M) reduced the efflux of ammonia by 46.7 and 42.2%, respectively, suggesting an interaction of NH4+ with the basolaterally located Na+/K+ exchanger in which NH4+ appears to be able to substitute for K+. PMID- 2926355 TI - Alterations in the cell cycle characteristics of granulosa cells during the periovulatory period: evidence of ovarian and oviductal influences. AB - Granulosa cells at different stages of differentiation were collected from ovarian follicles and oviducts during the periovulatory period, and their nuclear DNA content was monitored by flow cytometry to establish their cell cycle characteristics (G0 + G1, S, G2 + M). The proportion of cells in the three phases of the cell cycle varied in characteristics patterns depending upon the time they were collected, before or following ovulation. Granulosa (cumulus) cells recovered from ovulated oocytes were mitotically inactive as shown by the large proportion of cells with a 2C amount of DNA and the absence of cells in S phase. The proportion of granulosa cells in G2 + M decreased when recovery from the oviducts was delayed. In contrast, granulosa (cumulus and/or mural) cells recovered from preovulatory follicles prior to luteinizing hormone (LH) exposure contained a considerable population of cells undergoing DNA synthesis, and a decreased proportion of cells with a 2C DNA content. Our findings indicate that granulosa cells undergo dynamic and characteristics changes in all cell cycle phases during the periovulatory period, within follicular and oviductal environments. Intrafollicular events appear to play a major role in controlling DNA synthesis, proliferation, and related cell cycle events in the granulosa cells. Flow cytometric techniques provide objective and detailed information on the cell cycle characteristics of granulosa cell populations at different stages of differentiation. Elucidation of the mechanisms regulating cell cycle parameters of granulosa cells and their physiological significance thus seems feasible. PMID- 2926356 TI - Selective identification of the paternal mitochondrion in living sea urchin eggs and embryos by chlorotetracycline. AB - When sea urchin eggs are pretreated with fluorescent chelate probe chlorotetracycline (CTC) and then fertilized with unlabeled sperm, a small, brightly fluorescent particle resembling the mitochondrion of free-swimming sperm both in size and fluorescent staining characteristics appears in the egg cytoplasm. This particle first appears near the base of the insemination cone and, like the paternal mitochondrion identified in previous ultrastructural studies, remains closely associated with the male pronucleus during its microtubule-dependent migration toward the egg center. These similarities strongly suggest that the fluorescent particle observed in the cytoplasm of living, CTC-pretreated sea urchin eggs is, in fact, the mitochondrion of the fertilizing sperm. PMID- 2926357 TI - Ultrastructural localization of RFamide-like peptides in neuronal dense-cored vesicles in the peduncle of Hydra. AB - The presence of Arg-Phe-amide (RFamide)-like peptides in dense-cored vesicles in neurons of the peduncle of Hydra was demonstrated by immunogold electron microscopy. Thin sections of Lowicryl-embedded tissue labeled with antisera to RFamide and 5-nm gold-conjugated, secondary antibody and of Epon-Araldite embedded tissue labeled with 15-nm gold particles revealed a concentration of RFamide-like immunoreactivity over the granular cores of vesicles in epidermal ganglion cells. Gold-labeled, dense-cored vesicles were present in the perikaryon, long thin neurites, and axon terminals of these neurons. The aggregation of labeled dense-cored vesicles in an axon terminal on the myoneme of an epitheliomuscular cell suggests a possible function of RFamide-like peptides in neuromuscular transmission. Gold staining of dense-cored vesicles completely disappeared when the RFamide antiserum was preabsorbed with 10 micrograms/ml RFamide. These results are the first demonstration that the dense-cored vesicles of Hydra neurons contain a neuropeptide. PMID- 2926358 TI - Ability of various injuries to promote resorption of denervated, nerve independent regenerates of adult newts. AB - Young blastemas of the newt resorb if the limb is denervated, and are thus called "nerve dependent". Late bud and later stage regenerates are termed "nerve independent" because, while denervation inhibits their growth, they proceed through differentiation to form a normally patterned regenerate. Schotte and Liversage ('59) found that reamputation of a denervated nerve independent regenerate causes it to resorb. The present study asked whether injuries of varying severity are equally effective at promoting resorption. Newt forelimbs were amputated through the mid-radius/ulna. At nerve independent stages, the regenerates were denervated and injured in one of a variety of ways, then monitored for signs of resorption. Reamputation of the tip or incisions which created large gaps in the wound epidermis promoted resorption in 77-90% of the cases. Histology showed that the tissue removed by tip reamputation was a small proportion of the entire regenerate, suggesting that blastema resorption is not determined simply by the number of cells directly affected by the injury. Pin prick injuries, which created small disruptions of the wound epidermis, never caused resorption. Devascularization, caused by severing the brachial artery, promoted resorption in 17% of cases. These results are not consistent with the hypothesis that avascularity is a major causative factor in nerve dependence. PMID- 2926360 TI - A staging system for mouse limb development. AB - A series of 15 stages of development for the mouse limb bud have been defined, spanning the time from the first appearance of the limb bud to the completion of limb outgrowth. The stages are based on changes in the morphology of the limb in living preparations. The development and regression of the apical ectodermal ridge (AER) as well as the development of the skeletal structures are also described. This staging system has been developed in response to the need to standardize in situ experimental analyses of the mouse limb bud. Comparable stages of the commonly used chick wing and mouse whole embryo systems are presented. PMID- 2926359 TI - Role of the mouse visceral yolk sac in nutrition: inhibition by a somatomedin inhibitor. AB - A low molecular weight somatomedin inhibitory serum fraction (SI), obtained from streptozotocin-induced diabetic rats, causes morphological abnormalities and growth reduction in mouse embryos grown in whole embryo culture (WEC). These abnormalities are thought to be caused, at least in part, by a failure of the visceral yolk sac (VYS) to properly degrade proteins, a process that normally provides the conceptus with amino acids and peptides for de novo protein synthesis (histiotrophic nutrition). To test this hypothesis, embryos exposed to the SI were provided with a mixture of ten essential amino acids (supplemented group) in an attempt to circumvent SI-induced VYS dysfunction. Results showed that 82.4% (14/17) of embryos in the amino acid-supplemented group exhibited improved growth and development compared to those embryos exposed to medium containing the SI alone (unsupplemented group). Supplemented embryos showed greater expansion of the brain regions, improved visceral arch development, and increased protein content compared to nonsupplemented SI-treated embryos. However, these parameters were still reduced compared to controls. VYSs from both the unsupplemented and amino acid-supplemented groups were identical with respect to alterations in morphology and increased protein content compared to VYSs from conceptuses cultured in control medium (with or without amino acid supplementation). The improvement in embryonic growth and development due to amino acid supplementation in spite of VYS abnormalities supports the hypothesis that nutritional deprivation is one aspect of SI-induced teratogenesis. PMID- 2926361 TI - Mammalian limb bud development: in situ fate maps of early hindlimb buds. AB - Fate maps of the developing mouse hindlimb bud have been constructed for the first time using exo utero surgical techniques and carbon particle injections. Such fate maps demonstrate that the limb develops in a proximal to distal manner as a result of distal expansion. The anterior-posterior extent of the limb bud develops asymmetrically with the posterior half giving rise to slightly more of the digit pattern (digits 3-5) than the anterior half (digits 1 and 2). We found no evidence for the occurrence of extensive cellular rearrangements during limb development, and the free limb bud appears to give rise to only zeugo- and autopodial elements with the stylopod arising in the body wall proximal to the bud. These results are consistent with our current understanding of limb development in lower vertebrates and also provide detailed information that will be useful for future limb studies in mammals. PMID- 2926362 TI - Evidence for regulation following amputation and tissue grafting in the developing mouse limb. AB - Procedures are now available to experimentally manipulate postimplantation mouse embryos in situ and allow development to continue into postnatal life (Muneoka, K., N. Wanek, and S.V. Bryant (1986) J. Exp. Zool., 239:289-293). We have investigated the ability of the well-formed hindlimb bud to regulate following two experimental operations: amputation and wedge grafts designed to confront anterior and posterior cells. After comparing the resultant limbs with the fate maps of the relevant stages, we conclude that the developing hindlimb bud at stage 7/8 (equivalent to stage 27/28 of the chick) is capable of partial regeneration of the peripheral digits following amputation and capable of supernumerary digit tip formation after grafting of a wedge of anterior tissue to a posterior position. PMID- 2926363 TI - Failure of fertilization following abbreviated copulation in the ferret (Mustela putorius furo). AB - In the first experiment, copulations in 10 domestic ferrets were interrupted 5 minutes after penetration. Ten control females were bred without interruption to the same males. Both control and experimental animals were rebred in the same manner to the same males 24 hours later. Sperm were present in all postcoital washes. We allowed all females from the first experiment to proceed to their expected date of parturition. All females who had been interrupted during copulation failed to conceive, whereas all controls produced litters. In a second experiment, the same procedure was followed; however, in this experiment, ferret oviducts and uteri were flushed 10 days after copulation. Nine control females (one failed to ovulate) averaged 5.2 blastocysts (range 2-10; S.D. = 5.8) per animal. Of nine interrupted copulation ferrets (one failed to ovulate), only one animal produced a single blastocyst. The interrupted copulation group averaged 4.4 unfertilized eggs (range 2-10; S.D. = 5.0) per female. Although ferrets ovulated during short copulations, those eggs are not likely to be fertilized. PMID- 2926364 TI - A morphometric study of bone and tooth volumes in the pipid frog Xenopus laevis (Daudin), with comments on the importance of tooth resorption during normal tooth replacement. AB - Volumetric estimations of teeth and bone on serial sections using a semiautomatic image analyzer indicate that, in the polyphyodont dentition of the pipid anuran Xenopus laevis (Daudin), the mean volume of the dentine composing the teeth is about 23.5% of the volume of the supporting maxillae and premaxillae. During tooth replacement, osteoclasts resorb up to 98% of the dentine. Teeth may be resorbed rather than shed in order to conserve tooth constituents because, if shedding of complete teeth did occur, a quantity of calcified tissue equal to perhaps 45 times the volume of the bone of the upper jaw might be lost over an animal's projected life span of about 13-15 years. PMID- 2926365 TI - America's conscience--forever present. PMID- 2926366 TI - High-tech and high-priced medicine. PMID- 2926367 TI - A modest proposal for tort reform. PMID- 2926368 TI - Post-amendment 10 questions. PMID- 2926369 TI - Misleading information. PMID- 2926370 TI - Direct drag promotion does not benefit patients. PMID- 2926371 TI - More on geriatric education. PMID- 2926372 TI - Is teaching worth the risk? PMID- 2926373 TI - Management of vaginal vault prolapse: retrospective comparison of abdominal versus vaginal approach. AB - Twenty-two cases of vaginal vault prolapse were managed by our service over the five-year period ending 12/31/86. Eleven cases were repaired by a transvaginal sacrospinous colpopexy and 11 by a transabdominal suspension. There were no differences in demographic data or preoperative symptoms between these groups. The vaginal procedure required less operative time, had less blood loss, averaged fewer hospital days and overall was more economical. The complication rates and follow-up results of the two techniques were comparable. The abdominal procedure is considered preferable for patients with specific indications for an abdominal approach. The vaginal procedure appears to be more appropriate when the abdominal approach is not otherwise indicated. The experience of the surgeon and individualization of the patient are important factors in choosing the best approach for the repair. PMID- 2926374 TI - Profile of drowning victims in a coastal community. AB - Accidental drowning accounts for 15% of all accidental deaths in Pinellas County, Florida, and this study was conducted to better understand the epidemiologic profile of the victim. The medical examiner's records of 230 drownings in Pinellas County from January 1, 1983, through December 31, 1987, were reviewed for demographic and epidemiologic data. Bodies of salt water were the most common drowning site (47%), followed by swimming pools (22%), lakes (11%), baths (7%), and canals (6%). The drowning incidence for males was more than three times that for females. Drowning was endemic among boys less than five years of age (30/100,000/year). Fifty-nine percent of young adult victims had detectable postmortem blood alcohol levels. Drowning rates were highest among children less than five years and adults more than 80 years. Epidemiologic profiles of populations at risk and contributing factors are described and public safety measures are suggested. PMID- 2926376 TI - Of deformity. PMID- 2926375 TI - Health team networking: Alzheimer's disease care. AB - The expected increased incidence of Alzheimer's disease and related dementias in the next century will impact heavily on the care of physicians to involved families. Physicians alone cannot provide the assistance required by these families and need to access other health professionals and resources to assist these families. Responding to the desperate need for information by families concerned with Alzheimer's disease, physicians and other health professionals in North Central Florida networked to develop, implement, and evaluate a responsive strategy, a community forum on Alzheimer's disease and related dementias. The two hour daytime program with small discussion groups and a panel of experts for a question-answer session was highly successful and replicated. PMID- 2926377 TI - Identification reaction time as a function of target and field object orientation. AB - Four experiments were conducted investigating the effects of (a) target versus field object orientation, (b) target upside up versus target upside down and (c) inverting versus noninverting lenses on object identification reaction time. Inverting versus noninverting lenses had no significant effect. Target versus field orientation was significant when objects commonly found on a desk were used. Target upside up versus upside down was not significant. With letters as target and field objects, orientation was not significant. When the target letters were simply inverted (rotated 180 degrees on the horizontal axis), however, forming nonfamiliar patterns, the target upside up versus upside down was significant, with the upside down condition resulting in a longer mean reaction time. The complexity and similarity of target and field objects is offered as an explanation of the results. PMID- 2926378 TI - When shape information from a foveal nontarget affects gap detection accuracy in a parafoveal target. AB - Effects on gap detection accuracy of information at fixation concerning a parafoveally presented target form's global shape were determined in three experiments. Shape information was not directly relevant to the correct response regarding the presence of the gap. Tests were conducted to determine whether costs and benefits were associated with shape information, whether the effectiveness of shape information was sensitive to spatial attention, and whether subjects could volitionally suppress the nontarget information if it became apparent from preattentive analysis that it would not be helpful. Results were positive in all instances. Conclusions were that the foveal information was subject to early selection and that therefore it was not processed automatically. PMID- 2926379 TI - Delinquency, sidedness, and sex. AB - One hundred and thirty male and 213 female college students responded to a self report delinquency and crime measure and to a scale of sidedness preferences. Consistent with most of the literature on official delinquency and crime, left handedness was positively associated with involvement in several forms of delinquency (including some degree of criminality) among males. Other measures of sidedness among males largely failed to correlate with delinquency, however. Among females, sidedness was much less systematically related to delinquency than among males. PMID- 2926380 TI - Intraday feeding patterns in infant rhesus monkeys and the effects of missing a meal. AB - During the first month of life, infant rhesus monkeys (N = 96) were fed 7 times a day for the first 21 days and were fed 6 times a day thereafter. Fifty monkeys were fed SMA, a formula designed for human infants (9% protein, 43% carbohydrate, and 48% fat); 46 were fed one of three laboratory-confected diets varying in the amount of protein and carbohydrates provided. Although the diets had differential effects on weight gain, overall daily consumption was practically unaffected. A characteristic pattern was evident soon after birth: The first meal of the day (8:00 AM) was one of the largest, and the following two meals were usually the smallest; the next peak spanned the 4:00 PM and 8:00 PM feedings. The meal following a missed meal was slightly larger than normal. To some extent, the large meal at 8:00 AM can be attributed to the 10-hr absence of food during the night, but the peak at 4:00 PM and 8:00 PM cannot be so accounted for. The adult bicuspid pattern of eating hence appears to develop very early in life. PMID- 2926381 TI - The effects of formaldehyde on voluntary ethanol consumption in the laboratory rat: a comparison of two methods of determination of a single test solution. AB - The effect of formaldehyde on voluntary alcohol intake in rats was examined. Alcohol intake was measured using individually determined alcohol concentrations. The results did not support the tension reduction hypothesis: Stress induction did not enhance alcohol intake. It is concluded that a revision of the tension reduction hypothesis should be formulated. PMID- 2926382 TI - Different effects of the calcium antagonists nimodipine and flunarizine on dopamine metabolism in the rat brain. AB - The effect of two calcium antagonists, nimodipine and flunarizine, on striatal dopamine (DA) metabolism in rats was compared. Flunarizine (5-20 mg/kg i.p.) caused a dose-dependent increase in the DA metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC) in the caudate nucleus. Following the 20 mg/kg dose, DOPAC levels were maximally elevated by about 50% from 2 to 12 hrs after treatment. On the contrary, nimodipine at the dose of 20 mg/kg i.p. produced a modest decrease in DOPAC levels. Neither calcium antagonist modified DA content. However, both nimodipine and flunarizine, at the dose of 20 mg/kg, markedly reduced the accumulation of DOPAC in the caudate nucleus induced by haloperidol (1 mg/kg). It is suggested that flunarizine, but not nimodipine, has a neuroleptic-like action, whereas the two calcium antagonists have in common the ability to attenuate the hyperactivity of DA neurons. PMID- 2926383 TI - Dopamine in the rabbit retina and striatum: diurnal rhythm and effect of light stimulation. AB - In rabbits, dopamine levels in the retina, but not in the caudate nucleus, showed clear diurnal rhythm, with high values seen in the light phase. Thirty min exposition of dark-adapted rabbits to day-light produced no changes in dopamine levels in the retina. In rabbits treated with alpha-methyl-p-tyrosine, the same light exposition decreased the retinal amine level by 18%, while stimulation with intensive, flickering light significantly decreased the retinal dopamine content by 36%. Experiments performed at noon and midnight, under light or dark conditions, showed the retinal dopamine levels to be very similar in groups kept either at light or dark, irrespective of the time of the day, although in animals deprived of light the amine levels were clearly lower than in those exposed to light, both at noon and midnight. Under all experimental conditions there were no significant changes in dopamine level and utilization in the caudate nucleus. The isolated and superfused retina (preloaded with [3H]-dopamine), when stimulated with flashes of white light (2 Hz, 10 min), released [3H]-radioactivity in a Ca2+ dependent manner. It is concluded that in rabbits, light enhances dopamine levels and utilization selectively in the retina, and the observed diurnal changes in the amine metabolism are dependent on the presence or absence of light, and not on the time of the day. The proposed physiological role(s) of the retinal dopaminergic mechanisms is discussed. PMID- 2926384 TI - Cerebral excess release of neurotransmitter amino acids subsequent to reduced cerebral glucose metabolism in early-onset dementia of Alzheimer type. AB - A massive cerebral release of amino acids and ammonia was found in early-onset dementia of Alzheimer type. Aspartate and glycine were liberated in high concentrations, whereas glutamate remained rather unchanged. This excess cerebral protein catabolism is due to a 44% reduction in cerebral glucose metabolism. Whereas glutamate and other glucoplastic amino acids may substitute glucose, elevated aspartate may contribute to neuronal damage. The results are discussed with respect to a possible neuronal insulin/insulin receptor deficiency. PMID- 2926385 TI - Mosaic Drosophila wings reveal regional heterogeneity in the guidance of ectopic axons. AB - In most studies of axon guidance in the peripheral tissues of insects, the ability of experimentally perturbed axons to pathfind was examined only along their normal pathways. This means that regions normally devoid of axons have not been sampled for their ability to influence axonal trajectories. To examine this question, we have induced the formation of single sensory neurons in a variety of abnormal locations in the developing wing of Drosophila and have examined the course taken by their axons. The axons of such ectopic neurons have a regionally varying tendency to grow in the normal, proximal direction. This proximal bias approaches 100% for neurons located in the distal part of vein L2 and 70% in distal vein L4 but falls to chance (50%) along vein L5. Thus, neurons forming in ectopic regions of the wing, especially those found near the normal axon pathways (veins L1 and L3), have a high probability of growing axons in the correct direction. We conclude that information relevant to axon outgrowth is not restricted to the normal pathways. Whether this information is intrinsic or extrinsic to the neurons, and why its strength shows such conspicuous regional variation, awaits further study. PMID- 2926386 TI - Release of endogenous taurine and gamma-aminobutyric acid from brain slices from the adult and developing mouse. AB - The spontaneous and potassium-stimulated release of endogenous taurine and gamma aminobutyric acid (GABA) from cerebral cortex and cerebellum slices from adult and developing mice was studied in a superfusion system. The spontaneous release of GABA was of the same magnitude in slices from adult and developing mice, but the spontaneous release of taurine was considerably greater in the adults. The potassium-stimulated release of GABA from cerebral cortex slices was about five times greater in adult than in 3-day-old mice, but the potassium-stimulated release of taurine was more than six times greater in 3-day-old than in adult mice. In cerebellar slices from 7-day-old mice, potassium stimulation also evoked a massive release of taurine, whereas the evoked release from slices from adult mice was rather negligible. Also in cerebellar slices the potassium-stimulated release of GABA exhibited the opposite quantitative pattern. The stimulated release of both GABA and taurine was partially calcium dependent. The results suggest that taurine may be an important regulator of excitability in the developing brain. PMID- 2926387 TI - Lysosulfatide (galactosylsphingosine-3-O-sulfate) from metachromatic leukodystrophy and normal human brain. AB - The glycosphingolipid pattern was examined in three cases of late infantile metachromatic leukodystrophy (MLD): one with a relatively short (2.5 years), one with a long (7.8 years), and one with a very long (13.2 years) survival time. All values were compared with those of age-matched normal controls. The cerebroside concentration was reduced to 25, 12, and 4%, respectively, in the MLD white matter, whereas the sulfatide concentration was increased up to 200% of the control value. The yield of myelin was reduced to less than 15% in the early case and to less than 3 and 1%, respectively, in the two later cases. There was no sign of increased sulfatide proportion in the myelin. The ganglioside pattern was normal in cerebral gray matter, but in the white matter, contents of gangliosides of the lacto series were significantly increased, in particular, the ganglioside suggested by us as being characteristic of reactive astrocytosis. For the first time, lysosulfatide was identified in MLD and normal human brains by mass spectrometry and radioimmunoaffinity TLC using specific monoclonal antibody. Its quantity was found to be similar in normal and MLD brains. These findings support our postulation that the lysoglycosphingolipids are synthesized de novo from sphingosine and that they do not play a key role in pathogenetic mechanisms. PMID- 2926388 TI - Acidosis, acetazolamide, and amiloride: effects on 22Na transfer across the blood brain and blood-CSF barriers. AB - Sprague-Dawley rats were given treatments, known to decrease 22Na movement into choroid plexus and CSF, to investigate their effect on 22Na transfer across the cerebral capillaries. Acidic salts, acetazolamide, or amiloride was injected intraperitoneally into bilaterally nephrectomized rats, and the rate of 22Na uptake into parietal cortex, pons-medulla, and CSF was determined at 12, 18, and 24 min. Severe acidosis (arterial pH 7.2), produced by HCl injection, decreased the rate of 22Na entry into both brain regions and CSF by 25%, whereas mild acidosis (pH 7.3) from NH4Cl injection reduced brain entry by 18%, but CSF entry by only 10%. Like HCl acidosis, amiloride reduced transport into both brain and CSF by 22%. Penetration of 22Na into parietal cortex was unchanged by acetazolamide, but that into CSF was slowed 30%. Since uptake of 22Na into cortical regions is primarily movement of tracer across the cerebral capillaries when tracer uptake time is less than 30 min, the results indicate that both metabolic acidosis and amiloride decrease Na+ permeativity at the cerebral capillaries as well as at the choroid plexus. Acetazolamide, on the other hand, alters Na+ movement only across the choroidal epithelium. PMID- 2926389 TI - Ribonuclease activities and distribution in Alzheimer's and control brains. AB - Levels of free and total alkaline ribonuclease, and levels of acidic ribonuclease, were measured postmortem in control brains and in the brains of patients with Alzheimer's disease. In each brain region assayed, whether control or Alzheimer's, there was a statistically significant difference between the levels of free and total alkaline ribonuclease. Between 59 and 90% of the enzyme activity was associated with alkaline ribonuclease inhibitor in an inactive complex. Levels of free and total alkaline ribonuclease varied widely among different brains and brain regions, and were always lower in cerebellum than in temporal cortex and occipital pole. There was no significant difference in the levels of total alkaline ribonuclease, free alkaline ribonuclease, or acidic ribonucleases between corresponding regions of Alzheimer's and control brains. There was also no qualitative difference in the subcellular distribution of the alkaline and acidic ribonucleases between Alzheimer's and control brain. No significant relationships were found between ribonuclease levels and age, neuritic plaque density, postmortem interval, or storage time. PMID- 2926390 TI - Lipid metabolism during early stages of Wallerian degeneration in the rat sciatic nerve. AB - We examined changes in biosynthetic capacity of sciatic nerve during the early stages of Wallerian degeneration, utilizing a model that permits exclusion of nonresident cells from degenerating nerve. Sciatic nerve segments were placed in either 5-microns pore (allowing infiltration of nonresident cells) or 0.22 microns pore (excluding nonresident cells) Millipore diffusion chambers and then implanted in the peritoneal cavity of the same 32-34-day-old rat. At times up to 7 days postsurgery, nerve segments from the chambers, as well as control segments from the contralateral sciatic nerve, were removed and their capacity to incorporate radioactive precursors into lipids and proteins assayed in vitro. In nerve segments from both the 0.22- and 5-microns pore chambers, incorporation of [14C]acetate into total lipids was decreased relative to control by 50% at 12 h postsurgery and by 85% at day 3. This decreased incorporation of [14C]acetate reflects primarily decreased de novo synthesis of cholesterol and of fatty acyl residues incorporated into glycerolipids and sphingolipids. There was a preferentially decreased synthesis of cerebrosides and cholesterol (components enriched in myelin) relative to other lipids, while cholesterol esters and free fatty acids (products of membrane degradation) accounted for a greater proportion of the greatly reduced levels of total lipid label. In contrast to [14C]acetate, incorporation of [3H]glycerol into lipids was increased up to fourfold, relative to control, 1 day after nerve transection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2926391 TI - Binding characteristics of t-[35S]butylbicyclophosphorothionate in discrete brain regions of rats made tolerant to and dependent on pentobarbital. AB - The effects of acute and continuous pentobarbital administration by pellet implantation on binding characteristics of t-[35S]butylbicyclophosphorothionate ([35S]TBPS) in discrete regions of rat brains were examined. Acute administration of pentobarbital (60 mg/kg, s.c.) affected neither the KD nor the Bmax values of [35S]TBPS binding in any of the regions studied. The cerebella of pentobarbital tolerant rats had an increased density of [35S]TBPS binding sites with no change in their apparent affinity. There were no significant changes in the binding characteristics in the frontal cortex (FC), the striatum (ST), and the substantia nigra (SN) of these animals. Twenty-four hours after removal of the pentobarbital pellets, a significant decrease in the latency of onset of first twitch response induced by pentylenetetrazol (PTZ) (50 mg/kg, i.p.) was observed. In addition, the density of [35S]TBPS binding sites was significantly increased in the FC, the SN, and the cerebellum but not in the ST. In all brain regions studied, placebo pellet implantation and pentobarbital tolerance and dependence caused no changes in the apparent affinity of [35S]TBPS binding or the IC50 of pentobarbital for the inhibition of [35S]TBPS binding. These results suggest that [35S]TBPS binding was significantly increased following the withdrawal of the pentobarbital pellets without altering intrinsic coupling activity of barbiturate recognition sites and convulsant binding sites and that these increases in [35S]TBPS binding are related to the increased susceptibility to seizures induced by PTZ in rats made dependent on pentobarbital. PMID- 2926392 TI - Presence and measurement of imidazoleacetic acid, a gamma-aminobutyric acid agonist, in rat brain and human cerebrospinal fluid. AB - Imidazoleacetic acid (IAA) was unequivocally demonstrated in rat brain, human CSF, and human plasma by a gas chromatographic-mass spectrometric method that can reliably quantify as little as 8 pmol, i.e., 1 ng. Owing to tautomerism of the imidazole ring, IAA and [15N, 15N]IAA, the internal standard, each formed two chromatographically distinct isomers after derivatization of the ring nitrogens with either ethyl chloroformate or methyl chloroformate. The isomers of n-butyl(N ethoxycarbonyl)imidazole acetate and n-butyl(N-methoxycarbonyl)imidazole acetate were identified by analysis with methane chemical ionization and electron impact ionization of molecular and fragment ions. The levels (mean +/- SEM) of free IAA were 140 +/- 14 pmol/g and 2.7 +/- 0.2 pmol/ml in brains of untreated rats and human lumbar CSF, respectively. Mean levels of IAA in brains of anesthetized rats, perfused free of blood, did not differ significantly from mean levels of anesthetized, nonperfused controls or from untreated rats. The source or sources of IAA in brain and CSF are unknown. Because IAA is a potent agonist at gamma aminobutyrate receptors, it merits examination as a regulator in brain. PMID- 2926393 TI - Further physicochemical characterization of the novel human brain protein h3. AB - Recently we reported the isolation and partial biochemical characterization of the novel polypeptide h3 from human brain and liver. In this report, the physicochemical characterization is further established by the use of several analytical methods. The following results were obtained: the ultraviolet absorption spectrum is not influenced by pH, and the circular dichroism (CD) spectrum reveals that this protein has no alpha-helices, whereas approximately 25% of the polypeptide chain is found to be folded as a beta-pleated sheet structure. Neither the conformation of h3 as assessed by CD nor the titration kinetics of sulfhydryl groups with Ellman's reagent are affected by the presence of the ions K+, Na+, Ca2+, and Mg2+. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in a beta-mercaptoethanol gradient and Cleveland sequential SDS-PAGE showed that the frequent formation of h3 polymers and doublets, as observed earlier, is almost exclusively due to disulfide bonding. PMID- 2926394 TI - Protein fatty acid acylation in developing cortical neurons. AB - Neuron-enriched cultures derived from embryonic day 17 rat cerebral cortex were incubated in the presence of [3H]myristic or [3H]palmitic acid. Analysis of radiolabeled proteins by two-dimensional gel electrophoresis and fluorography revealed extensive incorporation of fatty acids into a small number of neuronal proteins. The major acylated proteins had apparent molecular weights and isoelectric points as follows: 87,000, 4.3; 63,000, 4.4; 45,000, 4.4; and 20,000, 5.3. After labeling with [3H]myristic acid, the radioactivity associated with these proteins was identified as myristic acid, which was attached via an ester linkage. All four of the major acylated neuronal proteins were found to be membrane-bound and enriched in growth cones. By virtue of its molecular weight, isoelectric point, subcellular distribution, and peptide map, the 87-kilodalton polypeptide was shown to be equivalent to pp80, a phosphoprotein that has been described in developing and mature synaptic terminals. The 45-kilodalton acylated protein also appears to coincide with another growth cone phosphoprotein, pp40. Acylation may serve as a mechanism to regulate the function of these proteins, or may play a role in directing them to the nerve terminal membrane. PMID- 2926396 TI - Acetylcholinesterase in mouse neuroblastoma NB2A cells: analysis of production, secretion, and molecular forms. AB - The mouse neuroblastoma cell line NB2A produces cellular and secreted acetylcholinesterase (AChE). After incubation of the cells for 4 days the ratio between AChE secreted into the medium and AChE in the cells was 1:1. The cell associated enzyme could be subdivided into soluble AChE (25%) and detergent soluble AChE (75%). Both extracts contained predominantly monomeric AChE (4.6S) and minor amounts of tetrameric AChE (10.6S), whereas the secreted AChE in the culture supernatant contained only the tetrameric form. All forms were partially purified by affinity chromatography. It could be demonstrated that the secretory and the intracellular soluble tetramers were hydrophilic, whereas the detergent soluble tetramer was an amphiphilic protein. On the other hand the soluble and the detergent-soluble monomeric forms were amphiphilic and their activity depended on the presence of detergent. By digestion with proteinase K amphiphilic monomeric and tetrameric AChE could be converted to a hydrophilic form that no longer required detergent for catalytic activity. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of [3H]diisopropylfluorophosphate-labelled AChE gave one band at 64 kilodaltons (kD) under reducing conditions and two additional bands at 120 kD and 140 kD under nonreducing conditions. PMID- 2926395 TI - Neurofilament phosphorylation in cultured bovine adrenal chromaffin cells is stimulated by phorbol ester. AB - Primary cultures of bovine adrenal chromaffin cells contain neurofilament proteins that are hypophosphorylated. When the cells were grown in medium containing 32Pi and 0.1 microM 12-O-tetradecanoyl-phorbol 13-acetate (TPA), 32P labelling of the three neurofilament subunits was increased 6- to 20-fold relative to controls, the highest level of stimulation occurring for the mid sized subunit. Addition of the protease inhibitor leupeptin to the growth medium had no effect on TPA-stimulated phosphorylation. The increased 32P incorporation was accompanied by a marked reduction in the gel electrophoretic mobilities of the two largest subunits. The augmented phosphorylation was observed 10 min after addition of TPA to a concentration of 0.1 microM or after 1 h of incubation in the presence of 0.01 microM TPA. One-dimensional peptide mapping and phosphoamino acid analysis indicated that TPA stimulated the phosphorylation of seryl residues at new sites in the mid-sized subunit. All of the latter subunit contained in the cytoskeletal fraction of chromaffin cells was converted to a more highly phosphorylated state after the cells were grown in the presence of TPA for 1 h. PMID- 2926397 TI - Isolation and sequence of a cDNA clone of beta-nerve growth factor from the guinea pig prostate gland. AB - The guinea pig prostate gland contains high levels of nerve growth factor similarly to the mouse submandibular gland. Nerve growth factor from the guinea pig prostate gland cross-reacts weakly with antisera directed against mouse nerve growth factor, is associated with different proteins, and may be processed by a different mechanism. We have isolated a full-length cDNA clone for nerve growth factor from a library prepared from RNA of the guinea pig prostate gland. The guinea pig cDNA contains 1,075 nucleotides and is very similar to the shorter of two predominant nerve growth factor transcripts present in the mouse submandibular gland. The cDNA sequence predicts a precursor protein of 241 amino acids that is 86% identical to the mouse amino acid sequence. Only 10 amino acid changes are present in the C-terminal region corresponding to the mature 118 amino acid beta-nerve growth factor of the mouse. Dibasic amino acid processing sites that are present at the N- and C-termini of the mature protein sequence and two other dibasic amino acid sites, representing potential processing sites within the propeptide, are all conserved, suggesting a similar mechanism of processing. PMID- 2926398 TI - Acrylamide-induced increases in deposition of axonally transported glycoproteins in rat sciatic nerve. AB - The axonal transport of proteins, glycoproteins, and gangliosides in sensory neurons of the sciatic nerve was examined in adult rats exposed to acrylamide via intraperitoneal injection (40 mg/kg of body weight/day for nine consecutive days). The L5 dorsal root ganglion was injected with either [35S]methionine to label proteins or [3H]glucosamine to label, more specifically, glycoproteins and gangliosides. At times ranging from 2 to 6 h later, the sciatic nerve and injected ganglion were excised and radioactivity in consecutive 5-mm segments determined. In both control and acrylamide-treated animals, outflow profiles of [35S]methionine-labeled proteins showed a well defined crest which moved down the nerve at a rate of approximately 340 mm/day. Similar outflow profiles and transport rates were seen for [3H]glucosamine-labeled glycoproteins in control animals. However, in animals treated with acrylamide, the crest of transported labeled glycoprotein was severely attenuated as it moved down the nerve. This finding suggests that in acrylamide-treated animals, axonally transported glycoproteins were preferentially transferred (unloaded or exchanged against unlabeled molecules) from the transport vector to stationary axonal structures. We also examined the clearance of axonally transported glycoproteins distal to a ligature on the nerve. The observed impairment of clearance in acrylamide-treated animals relative to controls is supportive of the above hypothesis. Acrylamide may directly affect the mechanism by which axonally transported material is unloaded from the transport vector. Alternatively, the increased rate of unloading might reflect an acrylamide-induced increase in the demand for axonally transported material. PMID- 2926399 TI - Species distribution of paraoxon-resistant brain polypeptides radiolabelled with diisopropyl phosphorofluoridate ([3H]DiPF): electrophoretic assay for the aged polypeptide of [3H]DiPF-labelled neuropathy target esterase. AB - Brain neuropathy target esterase is identified as a paraoxon-resistant, mipafox sensitive esterase that can be labelled with [3H]diisopropyl phosphorofluoridate. During "aging" of the labelled (inhibited) esterase, half the label (one isopropyl group) is transferred to a site (of the same molecular weight in sodium dodecyl sulphate) whence it may be released in volatile form by treatment with alkali. Our previously published procedure for complete extraction in a form suitable for scintillation counting of tritium-labelled proteins from polyacrylamide gels includes treatment of part-solubilised gels with alkali. Particles from brain of the hen, pig, sheep, guinea-pig, and rat were preincubated with paraoxon with or without mipafox, treated with [3H]diisopropyl phosphorofluoridate, and solubilised in sodium dodecyl sulphate. Labelled polypeptides (except from the rat) were separated by electrophoresis. Both mipafox-sensitive labelling and "volatilisable counts" were located principally in the 155-kilodalton region, with the residues dispersed throughout the gels. The quantities of paraoxon-resistant, mipafox-sensitive labelling sites and of "volatilisable counts" (in pmol/particles from 1 g) were, respectively, 12.2 and 8.65 in hen brain, 9.80 and 6.82 in pig, 8.48 and 5.46 in sheep, 4.46 and 4.01 in guinea-pig, and 4.91 and 2.08 in rat. The "volatilisable count" assay seems more specific for neuropathy target esterase and is easier and more precise than assays based on differences in labelling of two samples, each subjected to much processing. Hydrolytic activity of particles taken before labelling was measured against phenyl valerate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2926400 TI - Characterization of cellular transport, subcellular distribution, and secretion of the neurotoxicant 1-methyl-4-phenylpyridinium in bovine adrenomedullary cell cultures. AB - Cultures of bovine adrenomedullary chromaffin cells accumulated 1-[methyl 3H]methyl-4-phenylpyridinium ([3H]MPP+) in a time- and concentration-dependent manner with an apparent Km of 0.7 microM and a Vmax of 3 pmol/min/10(6) cells. The uptake was sodium dependent and sensitive to inhibitors of the cell-surface catecholamine transporter. At low concentrations of MPP+, the subcellular distribution was identical to that of endogenous catecholamines in the catecholamine-containing chromaffin vesicles. However, at a higher concentration of MPP+, a larger proportion of the toxicant was recovered in the cytosolic fraction, with less in the chromaffin vesicle fractions. When cells were prelabeled with [3H]MPP+, at 1 and 300 microM, and then permeabilized with digitonin in the absence of Ca2+, there was a proportionally greater release of MPP+ from the cells labeled at the higher concentration of the toxicant. In the presence of Ca2+, cell permeabilization induced a time-dependent secretion of catecholamines and a parallel secretion of MPP+. Under these conditions, the secretion of endogenous catecholamines was unaffected by the presence of MPP+. When the permeabilization studies were carried out in the presence of tetrabenazine, a massive release of MPP+ was observed in the absence of Ca2+ and was not further increased by Ca2+. In intact cells prelabeled with 300 microM [3H]MPP+, the secretagogues nicotine and veratridine elicited a Ca2+ -dependent secretion of catecholamines and MPP+ from the cells in similar proportions to their cellular contents. Barium-induced release of both species was independent of external Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2926401 TI - Ca2+ regulates hormone secretion and proopiomelanocortin gene expression in melanotrope cells via the calmodulin and the protein kinase C pathways. AB - The mechanism by which Ca2+ regulates proopiomelanocortin (POMC)-derived peptide secretion and POMC mRNA levels was investigated in primary cultures of porcine intermediate lobe (IL) cells maintained in serum-free medium. POMC gene expression was evaluated by the dot blot hybridization assay with a 32P-labeled DNA probe complementary to the full-length sequence of porcine POMC mRNA. Treatment of IL cells for 24 h with the calmodulin (CAM) antagonists W7 and W13 reduced POMC mRNA levels by a maximum of 50% in a dose-dependent manner (ED50 approximately 10(-8) M). Accumulation of alpha-melanocyte-stimulating hormone (alpha-MSH) in the medium was also depressed by 50% after 8 h of treatment. The role of protein kinase C (PKC) was investigated by depleting the IL cell PKC content with phorbol ester treatment. Phorbol 12-myristate 13-acetate (PMA) at 5 X 10(-8) M induced a rapid translocation of cytoplasmic PKC activity toward the membrane. After 12 h of PMA treatment, PKC activity was undetectable in either the cytoplasmic or the particulate fractions. The same dose of PMA induced a time dependent decrease in POMC mRNA levels (50% inhibition after 24 h). The same effect was seen with the phorbol ester phorbol 12,13-dibutyrate at 5 X 10(-8) M, whereas the inactive phorbol ester 4 alpha-phorbol at 5 X 10(-8) M was without effect after 24 h of treatment. PMA treatment had a biphasic effect on alpha-MSH secretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2926402 TI - t-[35S]butylbicyclophosphorothionate binding sites in invertebrate tissues. AB - Specific high affinity binding of the cage convulsant t [35S]butylbicyclophosphorothionate (TBPS) was observed in membrane homogenates of housefly heads and crayfish abdominal muscles. [35S]TBPS binding in these two invertebrate tissues was inhibited by biologically active cage convulsants, picrotoxin analogs, and barbiturates. The housefly binding sites were inhibited most potently by several insecticides. Approximately 50% of total binding was displaceable by excess (0.1 mM) nonradioactive TBPS, picrotoxinin, ethyl bicyclophosphate, or dieldrin. Optimal binding assay conditions for housefly homogenates included pH 7.5, 22 degrees C temperature, 0.3 M chloride concentration, and incubation for 60 min; for crayfish homogenates, 4 degrees C temperature and 150-min incubations were optimal. Scatchard plots of equilibrium binding indicated one site in both tissues (KD = 50 nM, Bmax = 250 fmol/mg protein in housefly; KD = 25 nM, Bmax = 100 fmol/mg protein in crayfish). Association kinetics in housefly were consistent with one rate constant (k+1 = 8 X 10(6) M-1 min-1), but dissociation was described better by two rate constants (k-1 = 0.28 min-1 and 0.042 min-1; calculated KD values of 80 nM and 12 nM). Displacement by cage convulsants showed Hill numbers near 0.5, also consistent with two populations of affinity, while displacement by other drugs showed Hill numbers near 1.0. [35S]TBPS binding in insects was most potently inhibited by the insecticides dieldrin (IC50 = 50 nM), aldrin, and lindane (200 nM), in a stereospecific manner, consistent with this binding site being the receptor for biological toxicity. [35S]TBPS binding was also inhibited by relatively high concentrations of some pyrethroid insecticides, such as deltamethrin and cypermethrin (1-2 microM).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2926403 TI - Arthroplasty for the stiff or ankylosed knee. AB - Twenty stiff (range of motion, less than 50 degrees) and six ankylosed knees were replaced with the posterior stabilized condylar prosthesis and evaluated after an average of 4.5 years (range, 2.5-7.5 years). There were 81% good to excellent, 11.5% fair, and 7.5% poor results. The maximum overall degree of flexion improved from an average of 60 degrees before surgery to 85 degrees after surgery. Flexion contracture was reduced from 28 degrees to 7 degrees, and the total arc of motion significantly increased from 32 degrees to 78 degrees. Less motion was achieved in the ankylosed knees. A modified inverted V-Y quadricepsplasty was a useful approach to the knee in 11 cases. PMID- 2926404 TI - Comparison and optimization of three centrifugation systems for reducing porosity of Simplex P bone cement. AB - Simplex P bone cement was spun for 30, 60, and 120 seconds in three different centrifugation systems (I.E.C. HN-S II, I.E.C. clinical, and Johnson & Johnson) to determine whether differences among the three systems also produce differences in the improvement of the fatigue strength of the cement. The fatigue properties of the cement after centrifugation were also assessed when it was mixed with monomer that had been chilled to 0 degrees C. There were important and statistically significant differences in the fatigue life of Simplex P spun for the same duration in the different centrifuges. Simplex P prepared as recommended by the manufacturer had an average fatigue life of 15,143 cycles in the test system used. Optimum centrifugation among the techniques studied increased the fatigue life nearly fivefold, to the range of 71,000 cycles. Taking into account both the fatigue strength and the viscosity of the cement, the optimum centrifugation system for improving the fatigue life of Simplex P bone cement is the Miller cartridge containing two packs of cement spun in the IEC-HN-S II centrifuge. The authors recommend 30 seconds of centrifugation if the monomer is not chilled prior to mixing and 60 seconds if the monomer is chilled. PMID- 2926405 TI - Rigidity of initial fixation with uncemented tibial knee implants. AB - This study quantifies the in vitro motion occurring between bone and cemented and noncemented tibial components. Liquid metal strain gauges were used to measure the motion between the tibial component and bone at four locations in eight cadaver tibia at near-point cyclic loads ranging from 10 to 2,000 N. Two types of motion were observed: inducible displacement, which is reversible, followed the oscillating load and occurred in both cemented and uncemented tests, and liftoff or separation of the component and bone, which occurred only for the noncemented cases and remained even after removal of the load. For both motion types, noncemented tests exhibited significant (P less than .05) and dramatic increased interface motion compared to the cemented cases for all load types. The results suggest that the magnitudes of implant-bone interface separation at loads in the low physiologic range for noncemented implants can be sufficiently large to inhibit bony ingrowth into a prosthesis with an average pore size of 300 microns. PMID- 2926406 TI - Fracture of a fenestrated metal backing of a tibial knee component. A case report. AB - The case of a metal-backed tibial component that failed by metal fracture is reported. Fracture occurred through fenestrations in the metal plate surrounding the central metal stem. The fracture followed loss of bony support beneath the medial tibial plateau, which had allowed varus deformity of the replaced joint. A high tibial osteotomy procedure had preceded replacement of the joint. PMID- 2926407 TI - Nonconstrained total elbow arthroplasty. Development and results in patients with functional class IV rheumatoid arthritis. AB - Twenty-four nonconstrained total elbow arthroplasties (TEAs) in 20 patients with severe disabling functional class IV rheumatoid arthritis were reviewed retrospectively to determine the effects of their disease on the end result. The mean follow-up period was 6 years (range, 2-11 years). All planes of elbow motion improved after surgery (P less than .005), there was a highly significant reduction in pain and improvement in function (both P less than .005) and patient satisfaction was high. The severity of the disease does not appear to affect the end result when a nonconstrained TEA is used, and the results compare favorably with those of other series reported. PMID- 2926408 TI - Dissociation of a metal-backed polyethylene acetabular component. A case report. AB - A case of early failure of a total hip arthroplasty presenting as a dislocation is discussed. After failed attempts at closed reduction, an open procedure revealed that the polyethylene insert of the acetabulum had separated from its metal backing. The increasing use of metal-backed acetabular components in total hip arthroplasty produces another mechanical interface that may fail: the metal polyethylene interface. surgeons should consider this possibility in dislocations of total hip prostheses that cannot be reduced by closed means. PMID- 2926409 TI - Early femoral component loosening in DF-80 total hip arthroplasty. AB - Forty-seven DF-80 total hip arthroplasties performed in 40 patients were evaluated to determine the incidence and causes of early femoral component loosening. With an average 37.1-month follow-up period, 48.9% of the femoral components developed bone cement-bone radiolucent lines worrisome for stem loosening. Twenty-three percent of the stems had subsided and 4.3% had been revised. Radiolucent lines were apparent very early (average, 8.8 months). Statistical analysis revealed positive correlations between the use of the larger (45-mm) offset stem and both the appearance of radiolucent lines and stem loosening. Being male and tall also were associated with stem loosening. The causes for early DF-80 femoral component loosening could not be defined with certainty. The results of this study and a review of the literature suggest that failure may be a result of early biologic weakening of the proximal cement-bone interface combined with a stem design that maintains proximal bone loading. Metal debris did not appear to be a factor in loosening of this titanium alloy stem. PMID- 2926410 TI - Correlation of MRI images with histology in avascular necrosis in the hip. A preliminary study. AB - The role of MRI in identifying the tissue level changes in the femoral head was investigated in five patients diagnosed as having avascular necrosis by radiology, scintigraphy, and MRI (0.35 Telsa). Radiographic scoring by the Ficat and Arlet system showed one hip with stage I, one stage II, two stage III, and one stage IV changes. The histologic features of core biopsy specimens obtained during decompression of the femoral heads were compared to the preoperative T1 and mixed T1/T2-weighted MR images. The cores varied with respect to their distance from the subchondral bone (7-23 mm) and length (19-45 mm). At the subchondral end of the core tract, low T1-weighted images corresponded to marrow fibrosis (5 cases) and in three of five cases to increased trabecular bone volume (TBV = 44-50%). Subjacent areas of diffusely decreased MR signal corresponded to marrow fibrosis and necrosis, with a relatively normal TBV (17-28%). The distal ends of the core tracts showed normal fatty marrow and a normal MR signal. The observations affirm that the MR signal intensity is largely reduced as a function of marrow degeneration and loss of fat content, but the signal is not predictive of particular histotypic morphologic patterns. PMID- 2926411 TI - Hip arthroplasty after biplanar femoral osteotomy. AB - Hip arthroplasty in patients who have had previous biplanar femoral osteotomy (eg, Southwick) is a technical surgical problem. Distorted proximal femoral anatomy may make routine insertion of a femoral prosthesis impossible. The authors report the short-term results in three patients with hip arthroplasty after biplanar femoral osteotomy. The technique consists of a biplanar closing wedge osteotomy at the level of the lesser trochanter to correct the previous surgical deformity. The remaining proximal femur becomes a vascularized bone graft that is skewered by the femoral prosthesis, which also gains purchase in the medullary canal of the proximal femoral shaft. This technique allows restoration of anatomic femoral alignment and the use of standard prostheses with preservation of bone stock. The initial results have been very good. The appearance of the hip is very similar to that in primary hip arthroplasty. PMID- 2926412 TI - Nonconstrained total shoulder arthroplasty in patients with polyarticular rheumatoid arthritis. AB - A retrospective review of 114 patients with polyarticular rheumatoid arthritis who had 140 total shoulder arthroplasties revealed that 93% of the patients had excellent pain relief; however, improvement in active forward elevation averaged 34 degrees. Nearly one-half of the patients had significant rotator cuff pathology. Three-fourths of the patients had a press-fit type of humeral component, and 5% of these have had variable amounts of subsidence. None have been sufficiently painful to require a revision. Eighty-two percent of the glenoid components developed radiolucent lines during the follow-up period. One percent of these were definitely loose and 9% were probably loose. To date, none have been revised. Complications occurred in 7% of the shoulders, but no deep or superficial wound infections were noted. PMID- 2926413 TI - Non familial juvenile distal spinal muscular atrophy of upper extremity. AB - An uncommon variety of non familial, juvenile onset, spinal muscular atrophy with asymmetric distal upper extremity affection is described. One hundred and two patients with a one to 14 year follow up are analysed. Spinal muscular atrophies with a distal distribution are rare. However, in the past three decades, previously unrecognised varieties of neurogenic muscular atrophy have been described in Asia (Japan, India, Sri Lanka and Singapore) under a variety of names. These provide interesting data for discussion of Asian neurogenic muscular atrophies with distal affection, in the context of diseases of the motor neuron. PMID- 2926414 TI - A case-control study of transient global amnesia. AB - To evaluate risk factors and prognosis of transient global amnesia (TGA), three groups of 30 subjects each affected respectively by: (1) first-ever TGA; (2) first-ever transient ischaemic attack (TIA); (3) depressive neurosis, were compared. Prevalence of cerebrovascular risk factors was similar in patients with TGA and TIA, but significantly lower in the third group. CT showed more hypodense lesions in TIA patients than in those with TGA. In a mean follow-up of 36 months, five TGA patients experienced a TIA and three others had recurrence of TGA, but none suffered stroke or myocardial infarction. In the TIA group, four had recurrence of TIA, two suffered a stroke and two others a myocardial infarction, whereas none had TGA attacks. None of the patients of the third group had any ischaemic event during follow-up. The similar prevalence of risk factors, but the different prognosis between TGA and TIA patients, suggest that TGA is an ischaemic event, probably not triggered by thromboembolism but by a different, possibly vasospastic, mechanism. PMID- 2926415 TI - Pulmonary function in Parkinson's disease. AB - Pulmonary function was investigated in 31 consecutive patients with relatively severe Parkinson's disease. Clinical disability was assessed by Hoehn and Yahr scale, Northwestern University Disability Scale and Websterscore. All patients were on levodopa substitution therapy and used anticholinergics. Pulmonary function was investigated by spirography, determination of a maximal inspiratory and expiratory flow-volume curve and, when possible, maximal static mouth pressures were determined. Peak inspiratory and expiratory flow, maximal expiratory flow at 50% and maximal static mouth pressures were significantly below normal values. Vital capacity, forced inspiratory volume in 1 s and the ratio of forced expiratory volume in 1 s and vital capacity were relatively normal. Nine patients had upper airway obstruction (UAO) as judged by abnormal values for peak inspiratory flow, the ratio of forced expiratory volume in 1 s and peak expiratory flow and the ratio of maximal expiratory and inspiratory flow at 50%. Flow-volume curves were normal in eight patients; four patients demonstrated flow decelerations and accelerations (type A) and 16 had a rounded off flow-volume curve (type B). Type A can be explained by UAO and type B by a combination of decreased effective muscle strength and possible UAO. Overall results of pulmonary function tests in patients without any clinical signs or symptoms of pulmonary disease point to subclinical upper airway obstruction and decreased effective muscle strength in a significant proportion of patients. PMID- 2926416 TI - Defective concept formation in parkinsonians is independent from mental deterioration. AB - An extensive neuropsychological battery (the Mental Deterioration Battery) was utilized to distinguish, within a sample of 24 idiopathic Parkinsonians, those showing signs of diffuse mental deterioration (n = 9) from those without deterioration (n = 15). Performances of control subjects on a wide range of tests exploring mnesic, visuo-constructive, linguistic and general intellectual functions (n = 21) did not differ from analogous performances of Parkinsonians without signs of diffuse mental deterioration. The Wisconsin Card Sorting Test was then used to verify the hypothesis that a selective impairment of cognitive functions subsumed by the integrity of frontal lobes could be demonstrated in Parkinsonian patients. Our results provide evidence that in this task, defective performances are obtained by Parkinsonians and even by patients without signs of diffuse cognitive impairment. These findings seem to confirm that a deficit in concept formation, maintenance and shifting is largely independent of the dementia frequently noticed in Parkinson's disease. PMID- 2926417 TI - Evoked potentials, reaction time and cognitive performance in on and off phases of Parkinson's disease. AB - Seven patients with Parkinson's disease and severe motor fluctuations were studied with event-related potentials, reaction and movement times and neuropsychological tests while in "off" and "on" phases. While there was a significant decrement in the P300 latency of the event-related potentials and in the duration of movement time in the "on" phase, no significant differences between on and off phases were observed in reaction time and neuropsychological tasks. PMID- 2926418 TI - Visual contrast sensitivity in drug-induced Parkinsonism. AB - The influence of stimulus orientation on contrast sensitivity function was studied in 10 patients with drug-induced Parkinsonism. Nine of the 10 patients had at least one eye with contrast sensitivity deficit for vertical and/or horizontal stimuli. Only generalised contrast sensitivity loss, observed in two eyes, was stimulus orientation independent. All spatial frequency-selective contrast deficits in 15 eyes were orientation dependent. The striking similarity between the pattern of contrast sensitivity loss in drug-induced Parkinsonism and that in idiopathic Parkinson's disease, suggests that generalised dopaminergic deficiency, from whatever cause, affects visual function in an analogous way. PMID- 2926419 TI - Ischaemic brain damage is still common in fatal non-missile head injury. AB - A detailed neuropathological examination has been undertaken on a consecutive series of head injuries dying in the Institute of Neurological Sciences, Glasgow, between 1968-72 (151 cases) and 1981-82 (112 cases) in order to determine the frequency and distribution of any ischaemic brain damage. Ischaemic damage was found in the brains of 92% of the 1968-72 cases and in 88% of the 1981-82 cases: there was no statistical difference in the amount of moderately severe and severe ischaemic damage in the two groups, 55% and 54% respectively. There was evidence, however, that an increased number of patients with severe ischaemic brain damage was admitted in 1981-82 as a result of a changed admission policy of the Department of Neurosurgery that resulted in an increased detection of intracranial haematomas. It is concluded that ischaemic brain damage is still common after severe head injury, and it seems likely that it remains an important cause of mortality and morbidity. PMID- 2926420 TI - Delayed deterioration in patients with traumatic frontal contusions. AB - The clinical course of 18 head injured patients in whom CT had shown frontal contusions without diffuse brain injury or intracranial haematoma was reviewed. All 10 patients with unilateral frontal contusion made a good recovery. Only two of five patients with limited bilateral frontal contusions made a good recovery. Two of three patients with extensive bilateral frontal contusions deteriorated more than 24 hours after injury, and one died. Delayed deterioration is an important complication of extensive traumatic bifrontal contusions. PMID- 2926421 TI - Treatment of focal dystonias of the hand with botulinum toxin injections. AB - The effects of botulinum toxin injections have been studied on 19 patients with hand dystonia. The dystonic muscles were identified by clinical examination and EMG findings of localised bursts of muscle activation with fine wire electrodes during the tasks that precipitated the dystonia. Injections into the most active muscles were given to each patient every 2 weeks in increasing doses (up to 20 U the first week, up to 40 U the second week, and up to 80 U the third week) until performance improvement was achieved. Subjective improvement of cramping, pain and/or tension was associated with temporary weakness in injected muscles. Benefit was seen in 16 patients, lasted between 1 and 6 months, and was reproducible. PMID- 2926422 TI - Interictal regional cerebral blood flow during non specific activation test in partial epilepsy. AB - In order to investigate, during activation testing, the interictal cortical cerebral blood flows (rCBF) of epileptic patients suffering from complex partial seizures, 40 epileptic patients (divided into "lesional", this is, with abnormal CT findings, and "non lesional", that is, with normal CT findings) were submitted to rCBF measurements with the 133 xenon intravenous technique, at rest and during intermittent light stimulation (ILS). The findings compared with normal volunteers seem to demonstrate that, during ILS, (1) in non lesional patients, the suspected epileptic focus shows a significant rCBF increase (2) in lesional patients, the significant rCBF increases were not in the region of the suspected epileptic focus but in adjacent or in contralateral ones. It was concluded that activation interictal rCBF measurements are more useful than resting ones for the determination of epileptic foci when CT findings are normal and that the nature of the epileptic focus influences markedly the interhemispheric activation pattern. PMID- 2926423 TI - Cerebrospinal fluid lactate in patients with diabetes mellitus and hypoglycaemic coma. AB - Cerebrospinal fluid (CSF) lactate and pyruvate concentrations were determined in 20 patients with diabetes mellitus but without disturbance of consciousness and five who recovered from hypoglycaemic coma. CSF lactate was slightly but significantly higher in diabetes mellitus (1.78, SEM 0.04 m mol/l) than that in 15 control subjects (1.40, SEM 0.05 m mol/l). In those who recovered from hypoglycaemic coma, CSF lactate was markedly elevated to 2.45-4.43 m mol/l. CSF glucose concentrations, however, were substantially the same between treated hypoglycaemic and diabetes mellitus groups. These findings indicate that CSF lactate levels increase with glycaemic levels in diabetes mellitus owing to enhanced glucose influx into glycolytic pathway of the brain, and also increases in treated hypoglycaemic coma probably due to mitochondrial dysfunction or damage. PMID- 2926424 TI - Postural sway during retinal image stabilisation. AB - Posturographic measurements using a piezoelectric platform were made in normal subjects while wearing a combination of spectacle and contact lens providing partial stabilisation of the retinal image (RIS). The amount of postural sway seen while wearing the device at rest is intermediate between the "normal vision" and "eyes closed" conditions, and increases with increasing amounts of RIS. However, when large active head-and-eye movements are performed, postural sway is dramatically increased when using RIS, and is then worse than while performing the same task in the "eyes closed" condition. It is concluded that patients who use the partial-RIS device for the treatment of severe oscillopsia may benefit only when performing tasks in which the head is relatively still, such as reading, writing or watching TV. It is also proposed that the partial-RIS device can serve as a model in normal free-standing subjects for the postural effects of oculomotor disorders. PMID- 2926425 TI - Retrograde pyramidal tract degeneration in a patient with cervical haematomyelia. AB - Retrograde pyramidal tract degeneration has been described only very rarely in the human central nervous system. In most of these cases the thoracic or cervical corticospinal tracts were shown to have degenerated following long-standing, lower spinal cord lesions. In a 67 year old man, who lived 2 years following the rupture of a mid-cervical cavernous angioma, we observed such degeneration which reached as high as the pons. This axonal dissolution was much less manifest above the ponto-medullary junction. Large pyramidal cells of Betz were not identified in the precentral gyrus, suggesting that the parental soma of the damaged axons had undergone atrophic changes. Furthermore, the involvement of the so-called aberrant pyramidal tract in the pontine medial lemniscus indicated that retrograde degeneration had occurred there as well. PMID- 2926426 TI - Finger tremor in Parkinson's disease. AB - Finger tremor was investigated in 20 patients (age range 54-88 yr) diagnosed as suffering from idiopathic Parkinson's disease and six controls of a similar age and no known neurological abnormality. In nine of the patients tremor was not clinically obvious. When the tremor of these patients was recorded immediately after voluntary movement and subjected to instrumental analysis there were consistently observable differences from the controls. Such analysis may have diagnostic potential when there is clinical uncertainty. Surface EMG recordings were obtained from four patients. One patient had a large resting tremor with obvious reciprocating activity in flexors and extensors; in the others who had no symptomatic tremor there was reciprocating activity only after movement, and this died away in a few seconds as the induced tremor disappeared. PMID- 2926430 TI - Meningoencephalopathy following iopamidol myelography. PMID- 2926428 TI - Preparation of manual movements in hemiparkinsonism. AB - Twenty patients with asymmetric Parkinson's disease were studied in a reaction time (RT) experiment in which the performance of the more affected ("bad") hand was compared with performance of the less affected ("good") hand. Simple RT and choice RT were tested in separate blocks, and the benefit afforded by advance information in the simple RT condition (choice RT minus simple RT) served as a measure of motor preparation. RT was longer in the "bad" hand in both the simple RT and choice RT conditions. There was no difference in the effect of advance information between the two hands. It is concluded that slowness in RT movement initiation in Parkinson's disease is not due to a deficiency in motor preparation, and that intact basal ganglia function is not required for this stage of motor programming. PMID- 2926427 TI - The utility of testing tactile perception of direction of scratch as a sensitive clinical sign of posterior column dysfunction in spinal cord disorders. AB - Classical beliefs about the functions of the dorsal columns of the spinal cord have been attacked following recent evidence that position and vibration sensations may be carried in the dorsal spinocerebellar tracts. There is evidence that the one specific function of the dorsal columns is for the transmission of information concerning the direction of tactile cutaneous movement. Thirty normal controls, 43 patients with spinal cord disorders and 10 patients with functional disorders were examined prospectively using an easily administered "direction of scratch" protocol. Interpretation of the direction of a 2 cm vertical tactile cutaneous movement over the lower limbs was found to be accurate in normal controls and grossly inaccurate in patients with functional disorders, exceeding the error rate of guessing. Detection of direction of 2 cm scratch was moderately impaired in 11 of 13 patients with spastic paraparesis and preserved sensation to all other modalities and 23 of 24 patients with spastic paraparesis and impaired proprioception and/or vibration sensations. Direction of 2 cm scratch, proprioception and vibration sensations were preserved in the three cases with anterior spinal cord syndromes. It is proposed that tactile perception of direction of 2 cm scratch over the lower limbs is a sensitive sign of posterior column function which can be usefully incorporated into the clinical sensory examination in the evaluation of spinal cord disorders. PMID- 2926429 TI - Initial factors predicting survival in patients with a spinal cord injury. AB - A study is presented of a prospective analysis of survival rates in 157 patients with spinal cord injury consecutively admitted to the Pellegrin Hospital (University Hospital, Bordeaux, France). There was a 20% death rate, occurring in the first three months after injury. Three independent predictors of survival in patients with spinal cord injuries (age, initial conscious level and respiratory assistance) were found by analysis of the course of the disorder. PMID- 2926431 TI - Iatrogenic lumbar meningocoel after excision of a neurofibroma. PMID- 2926432 TI - Recurrent localised myositis. PMID- 2926433 TI - Rheumatoid nodule formation within the lumbar extradural space. PMID- 2926434 TI - Proceedings of the meeting of the Association of British Neurologists jointly with the Association of Soviet Neurologists. Leningrad, USSR, 25-28 May 1988. Abstracts. PMID- 2926435 TI - Proceedings of the first meeting of the British Neuropsychiatry Association. London, 8 July 1988. Abstracts. PMID- 2926436 TI - Transient feelings of compulsion caused by hemispheric lesions in three cases. PMID- 2926437 TI - Leukocyte glutamate dehydrogenase in patients with degenerative neurological disorders. PMID- 2926438 TI - A prospective study of acute idiopathic neuropathy II antecedent events. PMID- 2926440 TI - Polyamine biosynthetic decarboxylases in muscles of rats with different experimental myopathies. AB - The activities of the two polyamine biosynthetic decarboxylases (PBD), L ornithine decarboxylase (ODC) and S-adenosyl-L-methionine decarboxylase (SAMD), have been measured in quadriceps femoris of rats killed at different times after the induction of calciphylaxis- or serotonin(5-HT)-induced myopathy. Decreases in both PBD levels were observed at early times after both myotoxic treatments. Subsequent progressive increases in both enzyme levels were observed to nearly control values by 4 days after 5-HT administration. In the 5-HT-treated rats, the effects on the myocardial PBD activities were different from those in skeletal muscle, with no effect on ODC but much on SAMD, when rats were killed shortly after 5-HT injection. These results demonstrate that the time-course of the changes in PBD activities in quadriceps femoris mirrors quite well the successive occurrence of degenerative and regenerative processes during the calciphylaxis induced myopathy and the 5-HT-induced myopathy; it is 5-HT that is mainly responsible for the decreases in PBD levels observed in both experimental myopathies, since dihydrotachysterol alone was without any effect on PBD activity levels and 5-HT alone was effective; myocardial ODC reacts more slowly to 5-HT than quadriceps femoris ODC. PMID- 2926441 TI - Myasthenia gravis associated with multiple sclerosis. Epidemiological survey and immunological findings. AB - Patient registers on myasthenia gravis (94 patients) and multiple sclerosis (991 patients) from a population of 1.5 million were reviewed to find patients with both diseases. Seven potential candidates were found, but both diagnoses were confirmed in 2 women only. The first patient had also iritis, the second patient had, besides MG and MS, bronchial asthma and polyarthritis. Both neurological diseases had a relatively mild clinical course. Thymectomy relieved MG symptoms in both patients. Cerebrospinal fluid studies during the follow-up indicated immunoactivation within the central nervous system. Changes in cellular immunity were also noted. The HLA types were different. The combination of these two diseases appears to be more common than expected. PMID- 2926439 TI - Congenital nemaline myopathy. A clinical follow-up of twelve patients. AB - A clinical follow-up of 12 patients with congenital nemaline myopathy (CNM) is reported. The aims of the study were to characterise the disease further, to investigate the prognosis of CNM and the factors influencing it, to find guidelines for treatment and, through neuropsychological tests, electroencephalography and computed tomography of the head, to determine whether the central nervous system is affected. The following distribution of muscular weakness was constantly found: the weakest muscles were the facial muscles, the flexors of the neck and trunk, the dorsiflexors of the feet and the extensors of the toes. The distal limb muscles and the limb-girdle muscles were clearly weaker than the proximal limb muscles. No signs of involvement of the central nervous system were detected, and IQs showed a skew towards higher levels. The clinical state of health had deteriorated in 10 of the 12 patients and improved in 2. In addition to the grade of disease activity, prognosis seemed to be influenced mainly by the development of scoliosis and by the restricted respiratory capacity. Since no specific therapy is available for this disease, recommendations for the management of CNM include active rehabilitation and vigorous treatment of respiratory infections. Physiotherapy should focus especially on the maintenance of cardiorespiratory capacity and the prevention and treatment of scoliosis. Long periods of immobilisation should be avoided. PMID- 2926442 TI - Myopathy associated with desmin type intermediate filaments. An immunoelectron microscopic study. AB - The muscle biopsy performed in a 58-year-old woman with a myopathy involving pelvic girdle and lower limbs displayed unusual intermediate filament aggregates by light and electron microscopy. No cardiac involvement was detected. The filamentous aggregates selective for type 1 fibers were found in subsarcolemmal and intermyofibrillar areas closely related to Z bands. Immunohistochemical study by light and electron microscopy using polyclonal and monoclonal antibodies and avidin-biotin peroxidase method revealed that aggregates consisted of desmin filaments. Desmin positive material was unstained with vimentine antibodies. PMID- 2926443 TI - Five novel cell surface antigens of CNS neoplasms. AB - Optimal monoclonal antibody-mediated immunotherapy requires the identification of tumor-restricted cell surface antigens. We have identified and partially characterized 5 new monoclonal antibodies generated against malignant astrocytoma, medulloblastoma, neuroblastoma and melanoma which were used to define 5 neuroectodermal tumor antigenic systems. CNT/1 identifies a 57-kDa, heat stable, trypsin-sensitive neuroblastoma surface antigen, which is expressed intracellularly in many malignant gliomas, medulloblastomas, ependymomas, breast and ovarian carcinomas. CNT/2 reacts with a 130-kDa, heat-labile, trypsin- and neuraminidase-resistant antigen restricted to low-grade astrocytomas and malignant gliomas. CNT/11 reacts with a 70-kDa, heat-labile, trypsin-sensitive antigen coded for by a gene on chromosome 12, and is restricted to astrocytomas, neuroblastomas and sarcomas. CNT/8 identifies a heat-labile, trypsin-sensitive antigen whose gene has been localized to chromosome 15 and is expressed by neuroectodermal and mesodermally derived tumors and few epithelial cancers. The B2.6 antigen is identified only in terms of serologic reactivity with a subset of cultured astrocytomas and melanomas. Neuroectodermal tumor-associated antigens may be categorized as lineage-consistent, lineage-independent and putatively tumor-restricted in their expression. These restricted antibodies may be potentially useful reagents to consider for monoclonal antibody-mediated immunotherapy of CNS neoplasms. PMID- 2926444 TI - Antigenic phenotypes of cultured malignant astrocytomas: identification of lineage-consistent, lineage-independent and putative tumor-restricted antigenic expression. AB - The treatment of CNS neoplasms with monoclonal antibody-mediated immunotherapy optimally requires the identification of tumor restricted cell surface antigens. However, little is known regarding the antigenic phenotype(s) of malignant astrocytomas. The interrelated expression of four neuroectodermal tumor antigens, CNT/11, AJ8, A010 and CNT/2, has been studied in cultured malignant gliomas and correlated with anchorage independent growth, morphology, glial fibrillary acidic protein, and the surface expression of other antigens. Many of these latter antigens have been reported to be expressed by specific fetal and differentiated adult cell lineages or tissues, as well as certain classes of malignant tumors. The tumor-associated expression of these antigens may be broadly classified as lineage-consistent, lineage-independent or putatively tumor-restricted. Malignant glioma tumor antigenic heterogeneity represents the expression of neuroectodermal and non-neuroectodermal cell surface markers. The importance of this observation is 2-fold. Lineage-independent antigen expression may be an indication of altered genome regulatory processes within tumor cells, and thus reflect the degree of anaplasia. The identification of lineage-consistent and lineage-independent tumor associated antigens may contribute to the selection of "target" antigens and the prediction of toxicity for monoclonal antibody mediated immunotherapy. PMID- 2926445 TI - Choreo-acanthocytosis. AB - This is the first report from India of a family of 4 sisters and 3 brothers in whom the proband showed a complete form of the choreo-acanthocytosis syndrome, whereas the 2 brothers who had died earlier of this disease had no examination of their blood. The apparently healthy members of this family also showed acanthocytosis, suggesting that this is a multisystem disorder affecting cell membranes. PMID- 2926446 TI - Familial vestibulocerebellar dysfunction: a new syndrome? AB - Three members of a single family with the symptom of "motion sickness" showed rebound nystagmus, saccadic pursuit eye movements, defective optokinetic slow phase velocity and lack of fixation suppression of vestibularly induced nystagmus. One of them showed vestibular hyperreactivity and a gradual build-up of the optokinetic response. In absence of other abnormalities, these findings can be localized to the vestibulocerebellum (flocculo-nodular lobe). PMID- 2926447 TI - The S-100 protein in cerebrospinal fluid: a simple ELISA method. AB - A simple ELISA method is described for determinations of S-100 protein concentrations in CSF. The assay has a useful range of 200-3200 pmol/l. The precision of the ELISA was estimated using a pool of CSF. The coefficient of variation was 0.18 within assay, 0.17 between assay and 0.17 between day. The S 100 protein is stable in the CSF as no measurable differences in S-100 concentrations were observed in samples stored at room temperature for 2 days. No correlation between age and S-100 concentration was found when determinations were performed in CSF from neurologically healthy males. Furthermore, no changes of S-100 was observed in a lumbocisternal CSF gradient from patients with normal pressure hydrocephalus. Thus, the described ELISA represents an easy to handle and reliable method, well suited for routine determinations of S-100 protein concentration in the CSF. PMID- 2926448 TI - Hyperestrogenemia in neuromuscular diseases. AB - In order to elucidate the relationship between certain neuromuscular diseases and gonadal hormones, we measured the levels of serum estrogens and other sex-related hormones. The values were compared with those for age-matched controls. The cases, comprising bulbospinal muscular disease of the Kennedy-Alter-Sung type, Kugelberg-Welander disease, amyotrophic lateral sclerosis, and Duchenne muscular dystrophy, were all euthyroid males. The baseline levels of serum estrone were significantly higher in all of the patients than in age-matched normal subjects. Serum baseline testosterone, LH and FSH levels were all essentially normal, except low FSH levels in Duchenne muscular dystrophy. Since our patients had no overweight, liver or glandular abnormalities, we presume that the elevated serum estrone levels have resulted from increased peripheral androgen-to-estrogen conversion. PMID- 2926449 TI - Expression of class I and class II MHC antigens in neuromuscular diseases. AB - The distribution of HLA class I and class II antigens has been investigated in cryostat sections of a series of 200 skeletal muscle biopsy specimens from patients with various neuromuscular disorders. Normal muscle fibres expressed no detectable class I antigens, whereas muscle fibres of patients with inflammatory myopathies and Duchenne (DMD) and Becker (BMD) muscular dystrophy showed consistently strong expression. In other neuromuscular diseases expression of class I antigens was more variable. No expression of class I antigens was observed on muscle fibres in samples from fetuses "at risk" for DMD and BMD or from female carriers of these disorders. The immunocytochemical assessment of HLA class I antigen expression was confirmed by a quantitative radioimmunoassay which demonstrated a 3-fold increase in the level of expression in muscle samples from patients with DMD and juvenile dermatomyositis. Class II antigen expression was never observed on muscle fibres in biopsies from normal individuals or any of the neuromuscular disorders. However, these antigens were expressed by endothelial cells present in these samples. Muscle specimens from fetuses and early in postnatal life showed very limited expression of class II antigens. They were expressed at a reduced level by about 3 months of age, but strong expression of class II antigens was not observed until about 1 year of age. The mechanism of induction of class I antigen expression in diseased muscle is not known. The appearance of class I antigens on diseased muscle may make the affected tissue a target for cytotoxic T cells and may thus have a role in muscle fibre damage in inflammatory myopathies and the X-linked muscular dystrophies. PMID- 2926450 TI - Comparison of major cortical aminopeptidase activity in normal brain and brain from patients with Alzheimer's disease. AB - In order to develop a greater understanding of the importance of peptide catabolism in the intracellular protein degradation process in normal and pathological human brain, we have undertaken a systematic investigation of the aminopeptidase group of enzymes. Although a wide range of aminoacyl-7-amino-4 methylcoumarin derivatives (which are used to measure aminopeptidase activity) were hydrolysed by normal human cortical soluble extract, fractionation of the latter via anion exchange and gel filtration chromatography resolved only 4 separable aminopeptidase types (activity relative to alanyl aminopeptidase in parenthesis): alanyl (EC 3.4.11.14, 100%); arginyl (2 isoenzymes, EC 3.4.11.6, 15%); pyroglutamyl (EC 3.4.19.3, 4%); and leucyl (EC 3.4.11.1, 1%). Thus approx. 80% of the total soluble aminopeptidase activity in normal human cerebral cortex can be accounted for by a single enzyme, the major cortical aminopeptidase. The activity of this enzyme was measured in the soluble fraction prepared from 4 cortical regions (occipital, frontal, temporal and parietal) in a series of 8 patients with Alzheimer's disease and compared with corresponding data in 8 control normal patients. Although enzyme activity varied in these cortical regions, the activity in corresponding brain areas in the Alzheimer's disease and normal groups was very similar. These findings suggest that the characteristic neurodegeneration associated with Alzheimer's disease does not result from altered activity of the major cortical aminopeptidase in the cortical tissue of patients with this disorder. PMID- 2926451 TI - Quantitative analysis of amyloid fibril protein in systemic organs of patients with familial amyloidotic polyneuropathy. AB - The purpose of this study was to develop a quantitative method for variant transthyretin (also called prealbumin) in amyloid-laden tissues of familial amyloidotic polyneuropathy (FAP). The variant transthyretin was extracted by using 70% formic acid solution in which the protein was solubilized completely and rapidly. The quantity of the variant transthyretin was measured by a radioimmunoassay (RIA). An immunoreactive species detected in the tissues of FAP was confirmed to be the variant transthyretin by reverse-phase high-performance liquid chromatography. The quantity of the variant transthyretin in the thyroid gland of 2 FAP patients was 9.90 and 9.76 micrograms/mg tissue, and that of the kidney was 4.03 and 6.27 micrograms/mg tissue, respectively, while its quantity in the liver was only 0.15 and 0.12 microgram/mg tissue. We present here a quantitative analysis of the distribution and predominance of amyloid deposits in systemic organs of FAP. PMID- 2926452 TI - Immunoglobulins and complement components in 37 patients infected by HIV-1 virus: comparison of general (systemic) and intrathecal immunity. AB - Intrathecal (IT) immunity was assessed by simultaneous analysis of paired cerebrospinal fluid (CSF) and sera of 37 patients infected by human immunodeficiency virus-1 (HIV-1). Only 8 of these 37 patients had no neurological or neuropsychiatric symptoms. There were 3 prominent abnormalities observed: (1) IT IgA production occurred in 15 patients, IT IgM production in 14 patients, and IT IgG production in 34 patients. (2) IT Anti-HIV-1 antibody specific activity (ASA) was higher than in serum in 33 of the 37 patients indicating that IT synthesis of antibody specific for HIV-1 occurs even in asymptomatic patients; IT anti-HIV-1 antibody synthesis was not correlated with clinical severity or neurological involvement. IT anti-herpes simplex ASA was also higher than serum ASA in 6 patients indicating a possible associated herpes simplex virus infection. (3) IT production of the complement component C4 was found frequently and was highly correlated with increased serum C4. IT C3 levels were decreased in 21 of 37 patients indicating that complement activation is a frequent accompaniment of the IT immune response in HIV-1-positive patients. These results indicate a unique and localized IT immune response which is different from the pattern observed in the systemic immune compartment in HIV-1-seropositive individuals and from the pattern common to the other CNS infectious diseases. PMID- 2926453 TI - Normal rat serum cytotoxicity against syngeneic oligodendrocytes. Complement activation and attack in the absence of anti-myelin antibodies. AB - The role of complement in mediating oligodendrocyte and myelin injury has been investigated by studying the effects of normal adult rat serum on syngeneic cultured neonatal glial cells. Rat serum has cytotoxic activity directed against oligodendrocytes but not astrocytes, the potency of which increases with cell maturation. The effects of heat inactivation, decomplemented rat serum, EGTA treatment, removal of any possible anti-myelin antibody by absorption using syngeneic myelin and absence of surface staining for immunoglobulins on serum treated oligodendrocytes, C9 depletion and reconstitution, and oligodendrocyte staining for surface C9 demonstrate that this cytotoxicity is mediated by complement via antibody independent activation of the classical pathway and is membrane attack complex dependent. These findings significantly extend the previous demonstration of complement activation by extracted myelin, and may have significance for the pathogenesis of demyelinating diseases. PMID- 2926454 TI - A light and electron microscopical study of B-50 (GAP-43) in human intramuscular nerve and neuromuscular junctions during development. AB - The growth associated protein B-50 (GAP-43) is demonstrated in human intramuscular nerves and neuromuscular junctions by light microscopy and electron microscopy. Nearly all fetal endplates are shown to be immunoreactive for B-50. The percentage of B-50 positive endplates decreases significantly during the peri and neonatal period, but in children and adults a low percentage of B-50 positive endplates remains present. These data indicate that also in the human peripheral nervous system the expression of B-50 is developmentally regulated. PMID- 2926455 TI - Acute ventilatory failure in multiple sclerosis. AB - Life-threatening acute ventilatory failure has been considered to be a very rare manifestation of multiple sclerosis (MS) and only a few cases have been investigated clinicopathologically. We examined 4 patients with MS who developed acute ventilatory failure, accompanied by a constellation of neurological symptoms and signs that were consistent with midline ventral medullary lesions. All but one of them survived the episode with artificial ventilation over a period of 9-11 days. One of the remaining 3 patients died a year later from subsequently developed anoxic encephalopathy. Neuropathological examination of the 2 deceased cases revealed the suspected lesions in the medulla as well as widespread chronic and active MS foci, which were characterized by largely necrotic changes rather than by pure demyelination. MRI in another case revealed a lesion in the caudal medulla. The apparently not so rare occurrence of ventilatory failure among Japanese MS patients might be related to the known differences in pathological features between Japanese and Western MS patients. Since there is a good chance of recovery, early recognition of the symptom complex appears important in the assessment and treatment of such patients. PMID- 2926456 TI - Intervention strategies with multiproblem families. Part 1. A psychoanalytical approach. AB - This discussion has focused on intervention strategies based on psychoanalytical theory. Recognizing that the birth of a baby is a developmental crisis in a family, the CHN can use one of three basic approaches. The choice of approach depends upon the family's need and their ability to respond to the approach. Fundamental to all three approaches is the establishment of a therapeutic relationship based on commitment. The nurse needs to be clear with her- or himself and with the family on what that commitment is. PMID- 2926457 TI - Intervention strategies with multiproblem families. Part 2. A structural functional approach. PMID- 2926458 TI - The community health nurse and multiproblem families. PMID- 2926459 TI - Analyzing nurse-client interactions in family planning clinics. PMID- 2926461 TI - How values affect the mutual goal setting process with multiproblem families. PMID- 2926460 TI - Ethical reasoning: a basis for nursing care in the home. PMID- 2926462 TI - Evaluation of the palmar circulation by pulse oximetry. AB - The usual method of substantiating collateral circulation of the hand is with Allen's test. We used the pulse-detecting capability of the pulse oximeter to assess the presence of collateral circulation of the hand. Thirty-one patients undergoing radial artery cannulation for intraoperative monitoring were evaluated before cannulation with a modified Allen's test and by pulse oximetry. After the collateral circulation of the hand was tested by the modified Allen's test, a pulse oximeter probe was placed on the index finger. Both radial and ulnar arteries were occluded until no perfusion was detected by the pulse oximeter. The test was repeated twice on each hand, once for each artery. The time to reperfusion after arterial release was recorded. Reperfusion times greater than 15 seconds were considered abnormal. This sequence was repeated postoperatively after the radial artery cannulae were removed. A total of 68 tests were performed before cannulation; 3 showed an abnormal Allen's test, a finding confirmed by pulse oximetry evaluation. The Allen's test was indeterminate 13 times. In all of these cases, pulse oximetry demonstrated collateral blood flow. When collateral circulation was determined to be present by Allen's test, it was also found to be present with pulse oximetry. Three days after cannulation was discontinued, 8 patients had abnormal Allen's test results, a finding again confirmed by pulse oximetry evaluation. Of 15 patients with indeterminate Allen's test results, 12 had collateral blood flow determined by pulse oximetry and 3 had abnormal results. The ability of pulse oximetry to detect collateral circulation was significantly different (P less than 0.001) when compared with Allen's test both before and after radial artery cannulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2926463 TI - Sampling intervals for clinical monitoring of variables during anesthesia. AB - Although five minutes is the sampling interval mentioned by the American Society of Anesthesiologists for monitoring blood pressure and heart rate during anesthesia, most patients are monitored more closely by continuous auscultation and with the help of automated instruments. Yet this difference between the interval recommended and that actually used indicates that sampling intervals are not defined clearly enough. Therefore, we present three methods with which to determine sampling intervals during monitoring. To explore the feasibility of these methods we examined data gathered every 7.5 seconds during three typical, noncatastrophic physiologic perturbations induced in an anesthetized dog. We chose hypercapnia secondary to rebreathing, hypotension secondary to deep anesthesia, and hypoxemia secondary to a low concentration of inspired oxygen as realistic examples of what can occur during operation and anesthesia. We studied three variables: respired carbon dioxide, femoral arterial blood pressure, and oxygen saturation of hemoglobin (pulse oximeter). The data obtained during monitoring were subjected to three methods of analysis: (1) recording of sets of data, with various starting times, at five-minute intervals only (moving grid); (2) Fourier analysis; and (3) analysis of slopes. For the data of the experiment, the Fourier analysis yielded, on average, longer sampling intervals than did the analysis of slopes. PMID- 2926464 TI - Interference of automated electroencephalographic processing by an endocardial pacemaker. AB - This article reports a patient with an endocardial pacemaker undergoing a carotid endarterectomy in whom cerebral function was monitored by using processed electroencephalography (EEG). The EEG was processed by means of aperiodic analysis. The pacemaker generated an artifact that was identified on the processed EEG display and on the raw EEG display. During the time of carotid cross-clamping, a loss of EEG activity was noted on careful examination of the processed EEG and confirmed by referring to the raw EEG. Nevertheless, because of the presence of the artifact, the activity edge remained essentially constant despite the change in underlying EEG activity. The cross-clamp was released based on the observed change in EEG activity, yielding a return to baseline EEG activity. The surgeon elected to shunt the patient. The patient awoke without neurologic sequelae. This case serves to demonstrate the importance of referring to the raw EEG signal and the limitations of the activity edge in the presence of artifact. PMID- 2926466 TI - Can the Raman scattering analyzer compete with mass spectrometers: an affirmative reply. PMID- 2926465 TI - Automated measurements of isolated heart muscle contractions: effects of halothane, calcium, and magnesium on guinea pig left atrial muscle. AB - An in vitro method for automatically measuring muscle contraction force has been demonstrated in a study of the effects of the inhalation anesthetic halothane followed by calcium chloride or magnesium sulfate on isolated guinea pig left atrial muscle. An automated computer-controlled system was used to collect muscle contraction force waveforms and to analyze contraction waveforms for comparison of variables before and after drug administration. Two concentrations of halothane (0.5 and 1.5%) were administered to the atrial preparation for 30 minutes and followed by calcium chloride or magnesium sulfate. Six variables (latency, time to peak tension, peak tension, maximum rate of change of pressure, force time integral, and relaxation time) were automatically determined from averaged stimulus-response curves. Results were normalized and compared with controls administered only calcium and magnesium and with controls administered no drugs. The automated system greatly simplified data collection and accumulation and statistical analysis of multiple responses. The system made possible averaging and analysis of more data with less variability than is normally obtained with manual systems. The results confirm several known actions of these agents. Halothane prolongs latency (9 and 21% for 0.5 and 1.5% halothane, respectively) and shortens time to peak tension (6 and 17% for 0.5 and 1.5% halothane, respectively) and relaxation time (17 and 39% for 0.5 and 1.5% halothane, respectively). At high halothane concentrations (1.5%) calcium chloride shortens latency (10%) and prolongs time to peak tension (11%); magnesium sulfate prolongs latency (14%) and shortens time to peak tension (10%). PMID- 2926467 TI - Evaluation of the Datascope ACCUSAT pulse oximeter in healthy adults. PMID- 2926469 TI - The fate of bone marrow micrometastases in patients with primary breast cancer. AB - Using an immunocytochemical technique, micrometastases have been found in the bone marrow of approximately 26% of patients with primary breast cancer at the time of initial surgery. To determine the fate of these cells, both in patients receiving and not receiving adjuvant therapy, multiple bone marrow aspirates were repeated in 82 patients at a median time of 18 months after surgery but prior to overt relapse. In both treated and untreated patients micrometastases were only found in one of 45 (2%) and one of 37 (3%) patients, respectively. However, when multiple marrow aspirates were taken from patients with local recurrence the incidence of micrometastases was 19% (three of 16), and this increased to 30% (three of ten) in patients with disease at distant sites other than bone, and 100% (ten of ten) in patients with radiologically proven bony disease. Three of 11 (27%) patients in whom the primary tumor remained in situ while receiving adjuvant therapy before definitive surgery had micrometastases at the time of diagnosis and at follow-up 3 months later. These results suggest that many of the micrometastases from breast cancer patients are the result of "shedding" of cells from the primary carcinoma and that a proportion are not viable. The technique is currently insufficiently sensitive to accurately monitor adjuvant therapy in breast cancer patients. PMID- 2926468 TI - A prospective randomized comparison of continuous infusion fluorouracil with a conventional bolus schedule in metastatic colorectal carcinoma: a Mid-Atlantic Oncology Program Study. AB - One hundred seventy-nine patients with advanced measurable colorectal cancer not previously treated with chemotherapy were entered into a prospective randomized clinical trial by the Mid-Atlantic Oncology Program (MAOP) to compare two schedules of delivery for single-agent fluorouracil (5-FU). The "standard" treatment was a schedule commonly employed in clinical practice, namely, a daily bolus dose administered intravenously (IV) for five consecutive days and repeated at 5-week intervals. The investigational treatment was a continuous infusion of 5 FU administered 24 hours a day for a protracted time (10 weeks or more). Both treatments were continued until the development of disease progression or unless interrupted for toxicity. Using stringent objective criteria requiring independent confirmation of x-ray or scan-documented response, the tumor response rate reached 7% (six of 87) for the bolus arm and 30% (26 of 87) for the infusion arms (P less than .001). Toxicity was substantially different for the two arms with major leukopenia observed only on the bolus arm, 22% developing grade 3 (severe) or grade 4 (life-threatening) leukopenia with four sepsis-related deaths. Hand-foot syndrome was observed only in the infusional arm, requiring treatment interruptions and dose reductions in 24% of patients, but with little impact on quality of life. In spite of the major difference in objective response rate, overall survival for the two groups was comparable. Administration of 5-FU as a continuous infusion for protracted periods clearly improves the therapeutic index for this agent in patients with advanced colon cancer with respect to response rate and reduced toxicity. This schedule appears workable in the community setting and yields response rates similar to those reported for 5-FU with high-dose leucovorin, but without the gastroin testinal toxicity profile of the latter combination. PMID- 2926470 TI - Randomized trial of cyclophosphamide plus cisplatin with or without doxorubicin in ovarian carcinoma: a Gynecologic Oncology Group Study. AB - A randomized clinical trial was conducted in women with stage III ovarian carcinoma (less than or equal to 1 cm residual lesions), using cyclophosphamide plus cisplatin (CP) with or without doxorubicin. There were 349 evaluable patients, of whom 176 received CP while 173 patients received CP plus doxorubicin (CAP). Hematologic toxicity was almost identical. There was no significant difference in progression-free interval (PFI) (median, 22.7 months and 24.6 months), frequency of negative second-look laparotomy (30.2% and 32.8%), or survival (median, 31.2 months and 38.9 months) between CP and CAP, respectively. Thus, doxorubicin in the dose schedule employed does not improve combination chemotherapy of optimal stage III ovarian carcinoma. Several other findings, independent of treatment arm, were of interest. There was a significant difference in PFI and survival by residual disease category (yes v no) and by grade of differentiation (1 v 2 + 3). In multivariate analysis, age, residual disease at entry, cell type (clear cell carcinoma), and time from surgery to initiation of chemotherapy were significant predictors of survival. There was no difference in outcome comparing those who refused second-look with those who had a second-look. PMID- 2926471 TI - Adverse effects of intraperitoneal fluorouracil in patients with optimal residual ovarian cancer after second-look laparotomy: a Gynecologic Oncology Group Study. AB - Twenty-seven patients with ovarian cancer who had failed combination chemotherapy were offered intraperitoneal (IP) fluorouracil (5-FU) as salvage therapy in an attempt to ascertain the efficacy of such a therapeutic method. All patients had minimal residual epithelial cancer. The median number of treatment cycles was six. Major problems with dialysate inflow and egress occurred in ten patients and required discontinuation of therapy. An additional ten patients experienced hematologic toxicity with a median nadir WBC of 2,300/microL. Therapy was altered but not discontinued because of this complication. Other adverse sequelae, such as abdominal pain, were manageable with medication. IP 5-FU is technically feasible on a multiinstitutional basis in residual ovarian cancer, but its therapeutic role remains to be defined. PMID- 2926472 TI - Suramin: an anticancer drug with a unique mechanism of action. AB - We administered suramin, an anti-parasitic drug and reverse transcriptase inhibitor, to 15 patients with metastatic cancer. This compound is known to inhibit the binding of growth factors (eg, epidermal growth factor [EGF], platelet-derived growth factor [PDGF], tumor growth factor-beta [TGF-beta]) to their receptors and thus antagonize the ability of these factors to stimulate growth of tumor cells in vitro. There were no complete responses (CRs), four partial responses (PRs) (two of ten adrenal cortex, one of four renal, one of one adult T-cell leukemia-lymphoma [HTLV-1]), and two minimal responses (MRs) (two of ten adrenal cortex). Toxicity included proteinuria (14 patients), reversible liver function test abnormalities (eight), vortex keratopathy (five), adrenal insufficiency (three), coagulopathy secondary to increased circulating levels of glycosaminoglycans (11), and one case of a reversible acute demyelinating polyneuropathy resembling the Guillain-Barre syndrome. We conclude that suramin is an active agent in the treatment of metastatic cancer, and further work is necessary to define its scope. PMID- 2926473 TI - Myocardial infarction in patients treated with mantle radiotherapy. PMID- 2926474 TI - Psychosocial factors and cancer: analytic strategies that bias to the null. PMID- 2926475 TI - The duration of a life of quality should become the focus of "quality-of-life" studies. PMID- 2926476 TI - Membrane proteins of the nerve growth cone and their developmental regulation. AB - The membrane polypeptides of growth cone fragments ("growth cone particles," GCPs) isolated from fetal rat brain by subcellular fractionation have been analyzed in further detail. The major polypeptides of salt-washed GCP membranes detected by 1-dimensional gel electrophoresis (Ellis et al., 1985b) resolve in 2 dimensional gels as a spot of 52 kDa that comigrates with beta-tubulin and reacts with anti-beta-tubulin; a 46 kDa, pl 4.3, polypeptide (pp46) that has no equivalent in the soluble fraction and is identical to one of the GCP's major phosphoproteins (Katz et al., 1985) and to GAP43 (Willard et al., 1985); a spot of 42 kDa that comigrates with actin; and a species of 34 kDa (p34) without soluble equivalent. The prominent 38 kDa doublet identified in 1-dimensional gels is difficult to resolve in 2-dimensional gels. The major phosphoproteins pp80ac, pp46, and pp40 (Katz et al., 1985), as well as p34 partition into the oil phase of Triton X-114 extracts, suggesting that they are integral membrane proteins, at least in our experimental conditions. The properties of pp46 reported here are in conflict with the highly hydrophilic amino acid sequence predicted for GAP43/B50/F1 (Basi et al., 1987; Karns et al., 1987). Growth-cone and presynaptic membrane proteins are compared as follows. After eye injection of 35S-methionine, GCPs and synaptosomes are isolated from the target areas of optic nerve of fetal and adult rats, respectively. Polypeptides are separated by 1- and 2-dimensional gel electrophoresis and the radiolabeled species identified fluorographically. The comparison of labeled GCP and synaptosome polypeptides shows that all 5 major Coomassie blue-stained polypeptides of GCP membranes (52, 46, 42, 38, 34 kDa) are intensely labeled after eye injection. However, in synaptosomes, these polypeptides are weakly labeled if at all; instead, an intensely labeled polypeptide of 28 kDa, and several additional species not seen in GCPs, have appeared. Therefore, the major growth cone membrane proteins are developmentally regulated, and the rates of synthesis and transport into the axonal ending of neuronal polypeptides change dramatically at the time of synaptogenesis. PMID- 2926477 TI - Corollary discharge inhibition and preservation of temporal information in a sensory nucleus of mormyrid electric fish. AB - Knollenorgan electroreceptors in mormyrid fish are concerned with electrocommunication, i.e., with detecting electric organ discharges (EODs) of other electric fish. But knollenorgan electroreceptors are also activated by the fish's own EOD. Potential interference by such self-stimulation is blocked by an inhibitory corollary discharge in the nucleus of the electrosensory lateral line lobe (NELL), the first central relay of the knollenorgan pathway. This study used intracellular recording and staining to examine the mechanism of the corollary inhibition and the specializations in anatomy and physiology that permit the accurate relaying of temporal information about the EODs of other fish. Several events are recorded inside primary knollenorgan afferents in addition to a large orthodromic action potential. The additional events include small orthodromic electronic epsps, postsynaptic action potentials, and a corollary discharge inhibitory postsynaptic potential (ipsp) associated with the EOD motor command. These additional events are also recorded in NELL cells and almost certainly originate there. Electrical coupling between afferents and cells makes it possible to observe the events inside primary afferents. The corollary discharge ipsp in the cell is associated with a conductance increase and inverts rapidly when recorded with chloride-containing electrodes, supporting a hypothesis of GABA mediation. The ipsp lasts longer in cells than in afferents. Each electrotonic excitatory postsynaptic potential (epsp) is probably caused by a single primary afferent, and any one of several epsps in a given cell seems capable of eliciting a postsynaptic spike in that cell. The epsps follow stimulation rates as high as 500/sec with minimal variability. No lateral inhibition is observed in NELL. These and other properties indicate that the knollenorgan pathway is specialized for temporal information rather than spatial or intensity information. PMID- 2926478 TI - Expansion of the central arborizations of persistent sensory neurons during insect metamorphosis: the role of the steroid hormone, 20-hydroxyecdysone. AB - During insect metamorphosis many larval neurons persist but are modified to serve new behavioral roles at later stages of life. For example, certain larval mechanosensory neurons expand their central arborizations during pupal development and evoke a different behavioral response, the gin trap reflex. The role of the insect steroid hormone, 20-hydroxyecdysone (20-HE) in this developmental change was investigated by removing the normal source of the hormone, followed by topical application of 20-HE to the peripheral somata of the sensory neurons. In prepupal animals that were ligated between the abdomen and thorax to remove the source of ecdysteroids the sensory neurons retained a larval arborization pattern. Topical application of 20-HE to the peripheral sensory neuron somata caused the treated neurons to undergo terminal arbor expansion within the CNS. The treated sensory neurons were not able to evoke the normal pupal behavioral response, but instead caused a larval-like reflex response. In a previous study, sensory neurons that were treated peripherally with a juvenile hormone analog during the commitment peak of ecdysteroids were shown to retain a larval arborization pattern at pupation and to not evoke the gin trap reflex (Levine et al., 1986). Within 4 d of pupation, however, these neurons belatedly developed expanded terminal arbors and evoked the pupal reflex. In the present study, similarly treated animals were ligated at pupation to block the surge in ecdysteroids that normally occurs at this time. This treatment prevented both the delayed expansion and the reflex, whereas topical 20-HE application induced growth and allowed the treated sensory neurons to evoke the gin trap reflex. It is concluded that both 20-HE and juvenile hormone act directly on the cell bodies of the sensory neurons to regulate the growth of their central processes. This growth is necessary but not sufficient for the development of the gin trap reflex, suggesting that other steroid-dependent changes must also occur within the CNS. Thus, as in the vertebrates, steroid hormones direct important developmental events within the insect nervous system. PMID- 2926479 TI - Evidence that glycine mediates the postsynaptic potentials that inhibit lumbar motoneurons during the atonia of active sleep. AB - Postsynaptic inhibition of somatic motoneurons underlies the atonia of active sleep. This inhibitory control depends, in large measure, on the bombardment of motoneurons during active sleep by a unique class of large-amplitude inhibitory postsynaptic potentials (IPSPs). These potentials are present only during this behavioral state and have therefore been designated as active sleep-specific IPSPs (AS-IPSPs). The present study was concerned with determining the neurotransmitter that mediates these AS-IPSPs. Lumbar motoneurons were recorded intracellularly during quiet and active sleep in intact, undrugged, normally respiring cats. The frequency and waveform parameters of the inhibitory postsynaptic potentials recorded from these motoneurons were examined following the microiontophoretic juxta-cellular administration of strychnine (a glycine receptor antagonist) and picrotoxin and bicuculline (GABA receptor antagonists). Microiontophoretically applied strychnine abolished the AS-IPSPs and a majority of smaller-amplitude IPSPs. Neither picrotoxin nor bicuculline modified the frequency, amplitude, or rising phase of the AS-IPSPs or the smaller-amplitude IPSPs. We conclude that the postsynaptic inhibitory drive that impinges on motoneurons during active sleep is principally mediated by glycine or a glycinergic substance. PMID- 2926480 TI - Stable and dynamic forms of cytoskeletal proteins in slow axonal transport. AB - Dynamic organization of the axonal cytoskeleton was investigated by analyzing slow axonal transport of tubulin and other major cytoskeletal proteins in the motor axons of rat sciatic nerve 1-4 weeks after injection of L-35S-methionine into the anterior horn area of L3-L5 lumbar spinal cord. A large proportion (50 65%) of tubulin transported in the axon was found to be insoluble when extracted with 1% Triton at 4 degrees C. This cold-insoluble tubulin was also resistant to other microtubule-destabilizing agents such as Ca2+, colchicine, and nocodazole, suggesting that it corresponded to the stably polymerized tubulin specific to the axon. From the cold-soluble fraction, microtubules containing a distinct set of associated proteins were recovered by the taxol-dependent procedure. Transport pattern of cold-soluble and -insoluble tubulin in this system showed a time dependent broadening of the tubulin wave resulting in the appearance of a new faster wave enriched in cold-soluble tubulin. The slower and the faster waves of tubulin were defined as group V or slow component a (SCa) and group IV or slow component b (SCb), respectively, with respect to the 2 subcomponents of slow transport originally described in the optic system. However, compositions of groups IV and V in sciatic motor axons differed significantly from those of the optic system. Actin also exhibited a clear dual wave pattern of transport that coincided well with that of tubulin, indicating that both actin and tubulin were the major components of both groups IV and V.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2926482 TI - Chromatic and achromatic vision of macaques: role of the P pathway. AB - Chromatic and achromatic contrast sensitivity were measured in a human observer, 2 normal macaque monkeys, and 3 monkeys with severe toxicant-induced damage to the parvocellular projecting retinogeniculate pathway (P cell-deficient monkeys). Damage to the P pathway was produced by the oral administration of acrylamide monomer (Eskin and Merigan, 1986). Contrast sensitivity was measured in all subjects with isochromatic luminance gratings, as well as isoluminant chromatic gratings, modulated along several directions of a color space that represents color-opponent and luminance contrast (Krauskopf et al., 1986). The chromatic and achromatic sensitivity of the control monkeys was virtually identical to that of the human observer. Chromatic sensitivity of the P cell-deficient monkeys, measured at a low spatial frequency (0.3 c/deg), along a constant-blue color axis, was 0.9-1.5 log units lower than that of controls. Similar losses were seen along a tritanopic confusion axis and along 2 intermediate axes of color direction. Chromatic thresholds measured at higher spatial frequency (2.0 c/deg) were similarly reduced. Counterphase-modulated chromatic gratings were used to test color sensitivity over a range of temporal frequencies up to 15 Hz, and the loss of color vision was substantial over the entire range of frequencies. The luminance contrast sensitivity of the P cell-deficient monkeys for stationary gratings decreased after exposure by 0.5-0.8 log units. These results indicate that the chromatic and achromatic spatial vision of macaques is very similar to that of humans. They also suggest that the P pathway plays an important role in macaque chromatic sensitivity at all spatial frequencies, as well as achromatic sensitivity at high spatial and lower temporal frequencies. PMID- 2926481 TI - Astrocytes cultured from mature brain derive from glial precursor cells. AB - We have previously shown that enriched preparations of oligodendrocytes from either mature bovine brain or 30-d-old rat brain, when cultured in serum-free medium, yield mixed cultures of oligodendrocytes and astrocytes even though no GFAP+ cells were present after 24 hr in culture (Norton et al., 1986, 1988). To test the possibility that the astrocytes in these cultures arose from glial precursor cells, we followed the expression of ganglioside GD3, galactosylceramide (GC), glial fibrillary acidic protein (GFAP), and vimentin in the cultures. GD3 has already been shown to be a marker of immature neuroectodermal cells, which in the postnatal brain are glial progenitor cells (Goldman et al., 1984, 1986). The cultures from both species contained at 1 DIV only two populations of cells; 90-95% GC+/GD3- oligodendrocytes and 4-10% GD3+/GC small, round cells. With time, the oligodendrocytes remained GD3-/GFAP-/vimentin . The kinetics of antigen expression of the GD3+ cells could best be interpreted by the following sequence: (sequence; see text) We interpret these results to show that the astrocytes arose from a small population of GD3+ glial precursor cells present in the brain that were co-isolated with oligodendroglia. No evidence was obtained that these GD3+ cells could also differentiate into oligodendrocytes. PMID- 2926483 TI - The neurology of memory: quantitative assessment of retrograde amnesia in two groups of amnesic patients. AB - The phenomenon of retrograde amnesia has important implications for understanding normal memory as well as its neural organization. Using 6 tests of remote memory, we evaluated the extent and severity of retrograde amnesia in 2 groups of amnesic patients--7 patients with alcoholic Korsakoff's syndrome and 5 other patients with amnesia (anoxia or ischemia, N = 3; thalamic infarction, N = 1; unknown etiology, N = 1). Although there were individual differences, Experiment 1 showed that the severity and extent of retrograde amnesia was similar for the 2 groups. Retrograde amnesia was temporally graded across a period of about 15 years and was not detectable in more remote time periods. In Experiment 2, repeated testing during a 3 year period showed that amnesic patients and control subjects were similarly consistent in their responses. Amnesic patients did not catch up to control subjects by eventually accumulating as many correct answers as the control subjects. In Experiment 3, amnesic patients performed normally on a test of very difficult general information questions, which were based on material likely to have been learned long ago. In all 3 experiments, the 2 groups of amnesic patients performed similarly. The results support the following conclusions: (1) Extensive, temporally graded retrograde amnesia, which has been observed frequently in patients with Korsakoff's syndrome, occurs readily in other amnesic patients as well, even when their memory impairment appears well circumscribed; (2) patients with presumed damage to either the medial temporal or the diencephalic brain structures linked to memory functions can produce a similar kind of retrograde amnesia; (3) the impairment reflects a loss of usable knowledge, not simply difficulty accessing an intact memory store that can then be overcome given sufficient retrieval opportunities; (4) very remote memory, at least for factual information, can be intact in amnesia; (5) the structures damaged in amnesia support memory storage, retrieval, or both during a lengthy period of reorganization, after which representations in memory can become independent of these structures. PMID- 2926484 TI - Amplitude fluctuations in small EPSPs recorded from CA1 pyramidal cells in the guinea pig hippocampal slice. AB - EPSPs have been evoked in CA1 pyramidal cells by (1) activation of single CA3 neurons (unitary EPSPs), and (2) low-intensity stimuli to the CA1 stratum radiatum. Five unitary EPSPs were obtained; their mean peak amplitudes ranged from 85 to 275 microV and 3 of the 5 showed fluctuations in amplitude that were too great to be attributed to baseline noise. After subtraction of the variance due to the noise, these EPSPs had coefficients of variation much higher than those reported for variability in the quantal EPSP in other preparations. These results suggest that intermittent transmitter release is a major cause of EPSP amplitude fluctuation at this synapse. A noise deconvolution technique based on a nonrestrictive model of transmitter release was applied to the EPSPs obtained in this study. For 2 of the EPSPs evoked by stratum radiatum stimulation, the amplitudes fluctuated between discrete values that were sufficiently separated with respect to the noise to be resolved by the deconvolution procedure. Quantal increments of 224 and 193 microV were determined for the 2 EPSPs. PMID- 2926485 TI - Cholinergic regulation of arterial pressure by the C1 area of the rostral ventrolateral medulla. AB - In anesthetized, paralyzed rats intravenous administration of the acetylcholinesterase inhibitor physostigmine (PHY) (100 micrograms/kg) evoked a dose-related rise in arterial pressure (AP) and heart rate (HR) and an associated increase in sympathetic nerve activity (SNA). The responses to PHY were blocked by electrolytic lesions of, or microinjection of kainic acid into, a specific site in the rostral ventrolateral medulla containing a cluster of neurons immunoreactive for the adrenaline-synthesizing enzyme phenylethanolamine N methyltransferase and corresponding to the C1 area of the nucleus reticularis rostroventrolateralis (RVL). The C1 area and its surround contain a heretofore unrecognized network of varicose neuronal processes and perikarya labeled immunocytochemically with a monoclonal antibody to the ACh-synthesizing enzyme, choline acetyltransferase (CAT). PHY increased, by over 3-fold, the spontaneous activity of reticulospinal cardiovascular neurons in the C1 area which excite preganglionic sympathetic neurons in the intermediolateral spinal column. The effects of PHY on AP, SNA, and the discharge of reticulospinal neurons were blocked by systemic administration of the muscarinic antagonist scopolamine. Microinjections within the C1 area of the RVL of scopolamine, the M2-selective muscarinic receptor antagonist AF-DX 116, or the high-affinity choline uptake inhibitor hemicholinium-3 blocked the pressor effects of PHY. The nicotinic antagonist hexamethonium and the M1-selective muscarinic receptor antagonist pirenzepine were without effect. We conclude that (1) the increases in AP, HR, and SNA elicited by the systemic administration of PHY result from the augmented action of ACh released from cholinergic terminals within the C1 area of the RVL; (2) the locally released ACh acts through muscarinic receptors of the M2 subtype within the C1 area to produce excitation of intrinsic reticulospinal sympathoexcitatory neurons, thereby increasing the activity of sympathetic preganglionic neurons and consequently elevating AP and HR; and (3) while the specific function of the cholinergic innervation of the C1 area in cardiovascular regulation is unknown, it may contribute to the tonic regulation of AP. PMID- 2926486 TI - Motor activity in the isolated spinal cord of the chick embryo: synaptic drive and firing pattern of single motoneurons. AB - The cellular mechanisms underlying embryonic motility were investigated using intracellular recording from motoneurons and electrotonic recording from muscle nerves during motor activity generated by an isolated spinal cord preparation of 12- to 15-d-old chick embryos. DC-coupled recordings from sartorius (a flexor) and femorotibialis (an extensor) muscle nerves revealed that both sets of motoneurons were depolarized at the same time in each cycle even when the motoneurons fired out of phase. Sartorius motoneurons fired briefly on the rising phase of the depolarization and then stopped firing before discharging a second burst of spikes as the depolarization decayed. By contrast, femorotibialis motoneurons fired at the peak of their depolarization, which was coincident with the interruption in sartorius activity. Intracellular recordings from antidromically identified motoneurons confirmed that flexor and extensor motoneurons were depolarized at the same time during each cycle of activity. The discharge of femorotibialis motoneurons, and others presumed to be extensors, followed changes in membrane potential so that maximal firing occurred during peak depolarization. The relationship between discharge and membrane potential was different in sartorius motoneurons (and in others presumed to be flexors) because they fired briefly on the rising phase of the depolarization and then stopped firing during peak depolarization. In some of these cells firing resumed as the membrane potential decayed back to rest. Intracellular injection of depolarizing current into sartorius motoneurons during motor activity reversed the direction of the membrane potential change from depolarizing to hyperpolarizing during the pause in sartorius discharge. In addition, the discharge evoked by the depolarizing current was blocked during the reversed part of the synaptic potential revealing its inhibitory nature. The occurrence of the IPSP was accompanied by a large reduction in motoneuronal input impedance. Injection of depolarizing current steps into motoneurons produced steady firing with no evidence of a pause in discharge, indicating that the depolarization accompanying synaptic activity was not responsible for the pause in firing of flexor motoneurons. These results suggest that flexor and extensor motoneurons receive a similar depolarizing drive from a common set of excitatory premotor interneurons. The alternating pattern of flexor and extensor discharge is produced, in part, by the timing of a depolarizing IPSP coincident with extensor activity that silences flexor discharge.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2926487 TI - An EM study of the dorsal nucleus of the lateral lemniscus: inhibitory, commissural, synaptic connections between ascending auditory pathways. AB - The dorsal nucleus of the lateral lemniscus (DNLL) and its connections constitute one of the ascending auditory pathways to the inferior colliculus. One notable feature of this nucleus is the heavy commissural connections between DNLL on opposite sides of the midbrain. These commissural connections may have a significant impact on the ascending pathway. In this study, the fine structure of DNLL in the cat and its commissural connections were examined. Both anterograde and retrograde transport methods were used simultaneously at the EM level. Injections of 3H-leucine mixed with WGA-HRP were made in one DNLL. After axonal transport, EM autoradiographic methods were used to identify the anterogradely labeled axonal endings from the opposite DNLL. In the same location, retrogradely labeled neurons with crossed connections were identified with HRP histochemistry. Two types of axonal endings were found in DNLL, those with round synaptic vesicles forming asymmetrical synaptic junctions and those with pleomorphic vesicles and symmetrical synapses. Both types were equally common. However, only endings with pleomorphic vesicles were labeled after injections in the contralateral DNLL. The labeled endings from the opposite DNLL appeared to represent a homogeneous population, even though a number of variations in the 2 types of endings were found. Labeled endings were presynaptic to all parts of neurons in DNLL, but a large proportion of the synapses were on cell bodies and large dendrites. Two patterns of nuclear morphology and distribution of rough endoplasmic reticulum were identified and may represent different cell types. Examples of both cell types were observed to project to the contralateral side and received labeled synaptic endings. The major finding of this study is that the crossed connections between DNLL exhibit the morphology associated with inhibitory function. Since neurons in DNLL are thought to use GABA as a neurotransmitter, the crossed connections could provide inhibitory inputs to DNLL on each side. Since some neurons receive numerous axosomatic inputs from the contralateral DNLL and also project to the opposite side, they may participate in direct reciprocal, inhibitory connections between the nuclei. Crossed inhibitory connections in the DNLL pathway may be important in regulating the flow of ascending auditory information. PMID- 2926488 TI - Deficits in response space following unilateral striatal dopamine depletion in the rat. AB - Hungry rats were trained to report the occurrence and location of brief, unpredictable visual stimuli presented to the left of their heads in 1 of 2 response locations. After training, they received unilateral infusions of 6 hydroxydopamine, depleting dopamine throughout the head of the caudate putamen, either on the left or the right side, that is, either ipsilateral or contralateral to the side on which they were required to respond. Following an ipsilateral lesion there were no impairments in localization of the visual discriminanda and there was no lengthening of reaction time. The contralaterally lesioned rats, however, showed considerably lengthened reaction times to both stimuli and a profound bias to the nearer of the 2 response locations. Evidence from probe trials in which the visual stimuli were presented separately or simultaneously showed that the impairment was not due to a failure to localize the stimuli in contralateral space but, rather, resulted from a deficit in directing responses in contralateral space. It is suggested that this may be due to a distortion in the representation of response space. PMID- 2926489 TI - Biosynthesis of adipokinetic hormones (AKHs): further characterization of precursors and identification of novel products of processing. AB - Two adipokinetic hormones (AKH I: pGlu-Leu-Asn-Phe-Thr-Pro-Asn-Trp-Gly-Thr-NH2, and AKH II: pGlu-Leu-Asn-Phe-Ser-Thr-Gly-Trp-NH2) are synthesized by the neurosecretory cells of the corpora cardiaca (CC) of the locust Schistocerca gregaria. Both AKHs are released into the blood during flight and serve to regulate lipid metabolism and other physiological processes involved in flight. By in vitro "pulse-chase" experiments we show that 2 precursors (P1 and P2) are involved in AKH biosynthesis. These are about 8.4 kDa polypeptides which are AKH immunoreactive but also contain an amino acid (tyrosine) not present in the AKH peptides. By following the fate of 14C-tyrosine incorporated into P1 and P2, we have identified 2 novel products of precursor processing. These are called AKH Precursor Related Peptides or APRP 1 and APRP 2. Size exclusion chromatography shows that the APRPs are about 6.5 kDa large and therefore represent major fragments of the precursors. The optical density peaks corresponding to P1, P2, APRP 1, and APRP 2 on a reverse-phase chromatogram are identified. The precursors being metabolic intermediates are represented by minor optical density peaks that disappear when de novo protein synthesis is blocked by cycloheximide. In contrast, the APRPs are represented by major optical density peaks consistent with their being accumulating end products of AKH precursor processing. The function of the APRPs is as yet unknown. They are, however, co-synthesized and also co-released with the AKHs, and may therefore also have hormonal functions related to flight. PMID- 2926490 TI - Neuropsychological deficit and emotional disturbance in head-injured patients. AB - The relationship between neuropsychological deficit and emotional disturbance was examined in a sample of 124 patients who sustained work-related head injuries. Most injuries met criteria for minor head injury. Since all patients were receiving compensation, the relationship between emotional disturbance and neuro behavioral deficit does not appear to be related to compensation or litigation factors. There was a positive relationship between degree of neurobehavioral and emotional abnormality. This was not due to the interval between injury and examination, and did not appear to be related to duration of unconsciousness or amnesia, or to the presence of skull fracture or posttraumatic seizures. The findings are discussed in relation to previous research and to their implications regarding posttraumatic emotional adjustment. PMID- 2926491 TI - Neurosurgical intervention in penetrating spinal trauma with associated visceral injury. AB - Associated injuries to the neck, chest, or abdomen are found in approximately one quarter of all civilians with penetrating spinal cord or cauda equina injuries. While the value of and indications for general surgical exploration and repair of these injuries are fairly self-evident, the value of neurosurgical intervention in terms of neurological outcome and infection prophylaxis remains the subject of debate. To study this issue, 160 civilian patients with penetrating spinal injuries and neurological deficits were retrospectively reviewed. Associated injuries of the esophagus, trachea, bronchi, or bowel were seen in 107 individuals (67%); 33 (31%) of these patients had abdominal injuries, 25 (23%) had neck injuries, 23 (21%) had thoracic injuries, and 26 (24%) had injuries occurring at multiple sites. Of these 107 patients, 67 (63%) had complete neurological injuries and the remaining 40 (37%) demonstrated incomplete deficits. All 107 patients underwent surgical exploration and repair of their visceral injuries; in 19 of them a neurosurgical procedure was also performed for decompression of the neural elements and/or debridement of the wound. Regardless of the presence of associated visceral injuries, the mechanism of injury, and the extent of the neurological deficit, no statistically significant difference in neurological outcome was found in patients with or without neurosurgical intervention. Complications associated with neurological injury were reported in 17 (11%) of the total group of 160 patients. Four (21%) of the 19 patients who had neurosurgical intervention suffered a related complication, compared to only six (7%) of the 88 patients who were managed conservatively (p less than 0.05). Within the limitations of a retrospective review, the results of this study do not clearly support the value of routine neurosurgical intervention as an adjunct to general surgical repair in cases of spinal injury associated with penetrating visceral trauma. PMID- 2926492 TI - Endoscopic surgery versus medical treatment for spontaneous intracerebral hematoma: a randomized study. AB - A controlled randomized study of endoscopic evacuation versus medical treatment was performed in 100 patients with spontaneous supratentorial intracerebral (subcortical, putaminal, and thalamic) hematomas. Patients with aneurysms, arteriovenous malformations, brain tumors, or head injuries were excluded. Criteria for inclusion were as follows: patients' age between 30 and 80 years; a hematoma volume of more than 10 cu cm; the presence of neurological or consciousness impairment; the appropriateness of surgery from a medical and anesthesiological point of view; and the initiation of treatment within 48 hours after hemorrhage. The criteria of randomization were the location, size, and side of the hematoma as well as the patient's age, state of consciousness, and history of hypertension. Evaluation of outcome was performed 6 months after hemorrhage. Surgical patients with subcortical hematomas showed a significantly lower mortality rate (30%) than their medically treated counterparts (70%, p less than 0.05). Moreover, 40% of these patients had a good outcome with no or only a minimal deficit versus 25% in the medically treated group; the difference was statistically significant for operated patients with no postoperative deficit (p less than 0.01). Surgical patients with hematomas smaller than 50 cu cm made a significantly better functional recovery than did patients of the medically treated group, but had a comparable mortality rate. By contrast, patients with larger hematomas showed significantly lower mortality rates after operation but had no better functional recovery than the medically treated group. This effect from surgery was limited to patients in a preoperatively alert or somnolent state; stuporous or comatose patients had no better outcome after surgery. The outcome of surgical patients with putaminal or thalamic hemorrhage was no better than for those with medical treatment; however, there was a trend toward better quality of survival and chance of survival in the operated group. PMID- 2926493 TI - Adult cerebellar medulloblastomas: the pathological, radiographic, and clinical disease spectrum. AB - The records of 34 patients over 16 years of age with cerebellar medulloblastoma were retrospectively reviewed. All patients were treated by surgery, and all surviving patients were given radiation therapy. The imaging characteristics of this rare entity were evaluated with regard to the tumor location in the cerebellum, and the prognostic effects of histological characteristics such as neuronal or glial differentiation and the presence of desmoplasia were investigated. Neither histological parameters nor tumor location (median, paramedian, or lateral cerebellar) affected patient survival. The desmoplastic variant was encountered in 38% of these adult medulloblastomas and occurred in all three cerebellar locations. The degree of surgical resection did not have a major effect on long-term survival; long-term survival was possible even in patients who had received only a biopsy. The extent of initial radiation therapy was positively correlated with recurrence-free survival; full neuraxis irradiation was associated with a 13% incidence of delayed spinal metastases, whereas 75% of patients treated with irradiation of only the posterior fossa and/or the whole brain developed spinal deposits. A similar local recurrence rate (12.5%) was noted in both irradiation groups. Chemotherapy resulted in palliation in some patients with metastatic disease. PMID- 2926494 TI - Cerebral aneurysms following radiotherapy for medulloblastoma. AB - Three patients, two males and one female aged 21, 14, and 31 years, respectively, developed cerebral saccular aneurysms several years after undergoing radiotherapy for cerebellar medulloblastoma at 2, 5, and 14 years of age, respectively. Following surgery, all three received combined cobalt-60 irradiation and intrathecal colloidal radioactive gold (198Au) therapy, and died from rupture of the aneurysm 19, 9, and 17 years after the radiotherapy, respectively. Autopsy examination revealed no recurrence of the medulloblastoma, but widespread radiation-induced vasculopathy was found at the base of the brain and in the spinal cord, and saccular aneurysms arose from the posterior cerebral arteries at the basal cistern or choroidal fissure. The aneurysms differed from the ordinary saccular aneurysms of congenital type in their location and histological features. Their locations corresponded to the areas where intrathecally administered colloidal 198Au is likely to pool, and they originated directly from a segment of the artery rather than from a branching site as in congenital saccular aneurysms. It is, therefore, concluded that the aneurysms in these three patients were most likely radiation-induced. PMID- 2926495 TI - Angiographic frequency of anterior circulation intracranial aneurysms. AB - A retrospective angiographic analysis was designed to extrapolate the frequency of angiographically defined asymptomatic intracranial aneurysms in the anterior circulation from a relatively unbiased clinical series. A total of 9295 angiograms were reviewed from January, 1980, to January, 1987, and, based on these, 278 patients with minimal bias for the presence of an aneurysm were selected. Three patients were found to have incidental aneurysms; thus, the angiographic frequency of patients with asymptomatic aneurysms in this series was 1%. This patient population is skewed toward the older age groups and probably over-represents the incidence of these aneurysms in the population at large. Comparing current subarachnoid hemorrhage statistics and the low frequency of asymptomatic aneurysms suggests that a larger percentage of these aneurysms than was previously thought subsequently rupture. This study contrasts sharply with previous reports quoting a high incidence of aneurysms, and significantly alters the concept and treatment of this disease. PMID- 2926496 TI - Regrowth of aneurysm sacs from residual neck following aneurysm clipping. AB - It is recognized that incomplete treatment of an aneurysm may result in recurrent hemorrhage with serious or fatal consequences. For this reason, patients treated at the authors' institution in whom a large portion of the aneurysm neck or sac remained after application of a clip or ligature have been subjected to reoperation. However, 1- to 2-mm residual necks seen in postoperative angiography have been thought to pose little risk. Some cases of aneurysms recurring from a narrow residual neck after clipping have been reported, and a few instances of recurrent aneurysm have been described after apparently complete occlusion of the neck (as observed angiographically or in the surgeon's judgment). In recent years, a surprising number of cases have been presented in which this seemingly unimportant remnant of the neck dilated over a long period to become a dangerous aneurysm. This finding stresses the importance of complete aneurysm occlusion and of postoperative angiography for the recognition of a residual aneurysm neck. This should be important not only in aneurysm clipping but also in the endovascular treatment of intracranial aneurysms with detachable balloons. PMID- 2926497 TI - Benign astrocytic and oligodendrocytic tumors of the cerebral hemispheres in children. AB - The authors review 42 consecutive cases of benign astrocytic and oligodendrocytic tumors of the cerebral hemispheres in children undergoing surgery in the pediatric service of the Hopital des Enfants Malades between 1975 and 1987. Epilepsy was the presenting sign in 76% of the children and remained the only clinical sign at diagnosis in 62%. Partial or complex partial seizures were observed in half of the cases, but other seizure types were also frequent. Diagnosis of the tumor as the etiological agent rested upon the results of computerized tomography or magnetic resonance imaging. Postoperative mortality (5%) and morbidity (16%) rates were low. The postoperative intelligence quotient was above 80 in 71% of the patients, and 77% of the children had no major problem in school. Although only two of the 42 patients were given postoperative radiotherapy, there were no recurrences in 82% of the survivors. The actuarial probability of nonrecurrence of the tumor was 95% at 5 years. Three patients with recurrent tumor underwent further surgery and are, at the present time, recurrence-free. The incidence of epilepsy fell from 76% before surgery to 19% after removal of the tumor alone; therefore, intraoperative electrocorticography and resection of the electrically abnormal cortex at the time of the first surgical procedure do not appear necessary. It is possible that tumor removal restores a mechanism that limits the spread of seizures and, thus, the clinical manifestations of epilepsy. Benign astrocytic and oligodendrocytic tumors of the cerebral hemispheres in children should not be treated with adjuvant radiotherapy, at least initially. PMID- 2926499 TI - Cerebral blood flow and the thermal properties of the brain: a preliminary analysis. AB - Safe and effective use of hyperthermia for the treatment of brain tumors requires precise control of the distribution of temperatures (that is, the thermal field) within the tumor and within the adjacent brain. Major influences upon the distribution of temperatures include the passive thermal properties of the brain, such as its specific heat (Cb), and the contribution of cerebral blood flow (CBF). Recently, an electrical-mechanical analog model of heat flow within the brain has been developed from which an expression for CBF has been derived: CBF = Cb/(tau rho c) where tau is the thermal decay constant, rho is the density of blood, and c is its specific heat. To test this model a series of experiments was carried out in adult dogs in which stereotaxically implanted microwave antennas operating at 2450 MHz, fluoro-optical thermometry probes, and platinum electrodes were used to simultaneously measure CBF by thermal washout and hydrogen clearance techniques. The correlation coefficient for estimates of CBF derived by the two methods in 52 paired observations was 0.89. Measurements of CBF were more reliable at increased distances from the microwave antenna, since CBF is sensitive to the degree of temperature elevation (delta T). The ratio of post heating CBF to pre-heating CBF varies linearly with delta T and has a correlation coefficient of 0.86. When values of CBF determined by the hydrogen clearance method were employed in the above equation, it was possible to derive Cb as 0.70 +/- 0.08 cal/gm-degrees C. Use of this value for Cb in this equation produces estimates of CBF by thermal clearance that are within 10% of the values for CBF as measured by the hydrogen clearance method. It is concluded that this model of thermal flow within the brain may have heuristic value for treatment planning and that microwave antennas and fluoro-optical probes may represent a new methodology for the clinical estimation of CBF. These methods have recently been employed in patients undergoing combined hyperthermia and chemotherapy. PMID- 2926498 TI - O6-alkylguanine-DNA alkyltransferase and sensitivity to procarbazine in human brain-tumor xenografts. AB - The level of O6-alkylguanine-deoxyribonucleic acid (DNA) alkyltransferase (AT) was determined in 15 human brain-tumor xenografts in athymic mice. This enzyme is a primary intracellular repair mechanism for lesions produced at the O6 position of guanine by a wide range of alkylating agents, including nitrosoureas and procarbazine. Its activity ranged from undetectable in five tumor lines to 2338 fmol/mg protein in N-1941, a human glioblastoma xenograft. The sensitivity of 10 of these xenografts to procarbazine was determined and it was found that four of the five tumor lines with AT levels of more than 100 fmol/mg protein had growth delays after procarbazine treatment of less than 20 days, whereas all five lines with undetectable AT levels had growth delays of over 30 days. The primary cytotoxic DNA adduct produced by procarbazine (namely, O6-methylguanine) was found to be significantly higher in two sensitive lines with low AT levels than in a highly resistant line with a high AT level. These data suggest that the AT levels of individual brain tumors can be used as predictive indicators of their susceptibility to drugs that exert their antineoplastic effect primarily by O6 alkylation of guanine in nuclear DNA. PMID- 2926500 TI - Effect of intracisternal antithrombin III on subarachnoid hemorrhage-induced arterial narrowing. AB - The ability of antithrombin III, an endogenous plasma glycoprotein, to reverse the arterial narrowing in a rabbit model of cerebral vasospasm was evaluated. The vasodilator activity of antithrombin III on rabbit arteries was first assessed in vitro using a myograph-arterial ring preparation. Antithrombin III (10 IU/ml) induced a 55.4% +/- 2.66% (mean +/- standard error of the mean) relaxation in basilar artery precontracted with serotonin (5-HT) in five specimens as compared with a 9.8% +/- 1.6% relaxation of common carotid artery in six specimens. For in vivo analysis, 21 New Zealand White male rabbits were separated into three groups: Group 1 served as normal controls; Group 2 received a subarachnoid blood injection (SAH) and were sacrificed on Day 3 thereafter; and Group 3 animals were subjected to SAH, then received a 2-hour intracisternal infusion of antithrombin III (100 IU) in saline prior to sacrifice on Day 3. Basilar artery caliber was determined using a morphometric method to analyze perfusion-fixed arterial segments. Control basilar artery diameter in Group 1 was 0.64 +/- 0.02 mm. In Group 2 a 27% reduction in arterial caliber to 0.47 +/- 0.03 mm was observed by Day 3 post SAH (p less than 0.0001). Group 3 animals had a mean basilar artery diameter of 0.68 +/- 0.02 mm. This was significantly larger than the untreated SAH rabbits in Group 2 (p less than 0.0001), but not different from control artery diameters in Group 1. The findings demonstrate that antithrombin III in saline has a significant ability to reverse delayed narrowing of the rabbit basilar artery after SAH. PMID- 2926501 TI - Spinal cord injury and the stress protein response. AB - The heat shock or stress response is a highly conserved primary cellular response to injury. Synthesis of stress proteins (also called "heat shock proteins") is an integral component of this response. Protection from various forms of sublethal stress following increased production of stress proteins has been demonstrated in a number of systems, including the retina. This immunocytochemical study demonstrates the synthesis, accumulation, and redistribution of the 70-kD stress protein following spinal cord injury in rats. The observations confirm that stress protein production is a fundamental feature of the molecular response of the spinal cord to injury, and raise the possibility that augmentation of this response could enhance posttraumatic neuronal survival. PMID- 2926503 TI - Inflammatory reaction to synthetic dural substitute. Case report. AB - The authors report an unusual complication related to a dural substitute. An inflammatory response to a Marlex mesh duraplasty simulated a recurrent convexity meningioma 20 years after the initial surgery. PMID- 2926502 TI - Magnetic resonance imaging and 31P magnetic resonance spectroscopy for evaluating focal cerebral ischemia. AB - Recent advances in magnetic resonance (MR) imaging and MR spectroscopy (MRS) allow the noninvasive in vivo study of a variety of anatomical, physiological, and biochemical alterations that may occur in different cerebral pathologies. The authors have investigated the use of MR imaging and MRS to monitor the evolution of experimental focal cerebral ischemia in rats. Permanent focal cerebral ischemia was induced in 36 rats, and 12 normal rats were used as a control group. Changes in high-energy phosphate metabolites were followed in vivo using MRS during the 1st hour and at 3 and 6 hours after ischemic insult. Changes in vivo MR images were evaluated at 1, 3, 6, 12, and 24 hours after ischemic insult. Significant decreases (p less than 0.05) in phosphocreatine/inorganic phosphate ratios and intracellular pH values occurred immediately after the induction of ischemia. The presence of an infarcted area seen on MR images was a constant finding at 3 hours after ischemic insult, and was well defined and localized at 12 and 24 hours. The location of areas of infarction seen on MR images correlated well with areas identified histopathologically. The T1 and T2 MR relaxation times were significantly increased 3 hours after ischemic insult and remained prolonged for at least 24 hours. The results show that MR imaging is a sensitive method to measure cerebral infarction, and that MRS is a sensitive measure of changes that occur in the early phases of ischemia, perhaps when cellular changes may still be reversible. At 3 and 6 hours after the ischemic insult, however, 31P-MRS spectra may appear to be "normal" despite the presence of well-documented areas of infarction. PMID- 2926504 TI - Familial os odontoideum. Case report. AB - A familial asymptomatic os odontoideum with a Klippel-Feil type II fusion of C-2 and C-3 is reported. The pattern of inheritance within this family is consistent with that of autosomal dominance. The index case, a 16-year-old boy, was studied with plain cervical spine x-ray films, lateral cervical tomography in flexion and extension, fluoroscopic evaluation of the subluxation, and magnetic resonance (MR) imaging of the spine in flexion and extension. In spite of the subluxation noted on flexion and extension, there was no evidence of cord compression on MR imaging. The etiology and management of this condition are discussed. PMID- 2926506 TI - Spinal meningioma arising from a lumbar nerve root. Case report. AB - A case is reported of cauda equina compression from an intradural meningioma arising from the L-5 nerve root in a young man. PMID- 2926505 TI - Hypothalamic hamartoma. Report of two cases. AB - Two cases of hypothalamic hamartoma are presented. The first patient was a 4-year old boy with precocious puberty, and the second was a 6-year-old boy with epileptic seizures. In both patients, clinical symptoms and signs appeared at the age of 2 years and progressed thereafter. Computerized tomography and magnetic resonance imaging in both cases disclosed a suprasellar mass lesion in continuity with the hypothalamus. Removal of the lesions affected the endocrinological status and/or seizure control. Pathological examination revealed the lesions to be composed of well-differentiated neuronal and glial cells. Immunohistochemical study demonstrated the presence of beta-endorphin, corticotropin-releasing factor, oxytocin, and neurofilament protein (210 kD) in the neuronal cells of the first patient, but no neuropeptides were detected in the second. Electron microscopic examination on the second patient disclosed the presence of many nonmyelinated and some myelinated neuronal processes containing dense-core and clear vesicles. The morphological characteristics and the role of surgery for this lesion are discussed. PMID- 2926507 TI - Quantification of retrograde degeneration in corticospinal tract fibers. PMID- 2926508 TI - Magnetic resonance imaging of acute SAH. PMID- 2926509 TI - Subarachnoid hemorrhage and intracranial pulse waves. PMID- 2926510 TI - Physician surcharge. Another barrier to practice. PMID- 2926511 TI - Leaking: a problem of lactation. AB - Monthly semi-structured interviews with 61 breastfeeding mothers over the duration of their nursing experience and in-depth interviews with nine additional mothers were conducted. At six months postpartum, 66% of the nursing mothers still experienced leaking breasts, and most mothers expressed negative feeling about leaking. Attempts to manage or control leaking milk were sometimes successful, but the unpredictability of leaking often undermined mothers' confidence and ability to stop or conceal leaking milk. To minimize leaking, mothers frequently used pressure on the nipples and consciously diverted their thoughts or used simple word commands to halt the let-down reflex. For those mothers who leaked for the duration of their nursing experience, coming to terms with leaking was an important part of their breastfeeding experience. Suggestions for further research and implications for practice are included. PMID- 2926512 TI - Nurse-midwives speak out on the ACNM. Results of the 1987-88 Needs Assessment Survey, Part 1. AB - This article presents the purposes and methods of the first Needs Assessment Survey of all nurse-midwives who have been certified by the ACNM. A detailed summary of the general results of the survey is provided, and includes the perceptions of respondents about the ACNM organizational structure, goals, leadership, and services. Analyses of differences in response based on such variables as membership status, minority status, years since certification, level of educational preparation, work setting, and region of residence are also presented. The article concludes with a discussion of the implications for the nurse-midwifery profession. Part 2 will appear in JNM 34:2. PMID- 2926513 TI - Chlamydia and trichomoniasis in pregnancy. Nurse-midwifery management. PMID- 2926514 TI - Anatomy of a training seminar. Teaching and learning in Angola. AB - Training and service delivery in maternal and child health are high priorities for Angola's national health system. Maternal and infant mortality are very high, and there is a severe shortage of physicians. Most reproductive health care is provided by nurses and midwives. Appropriate education, resources, and support can assist these professionals in their struggle to improve mother and infant outcomes. A teacher training seminar for experienced nurses and midwives was carried out in Luanda, Angola in the summer of 1988. Content focused on family planning, sexually transmitted diseases, and human sexuality. Teaching methodology emphasized participation, active learning, group work, and practice teaching sessions. The steps involved in the training process are described- including needs assessment, planning, implementation, and evaluation of the seminar. PMID- 2926515 TI - Closing of the nurse-midwifery service at Boston City Hospital. What were the issues involved? AB - This article describes the experiences of 11 staff CNMs practicing in an inner city hospital serving low-income women. A history of the conflicts between the OB/GYN Department and the Midwifery Service at Boston City Hospital is presented, as well as an overview of events in 1987-88 that resulted in the unanimous resignation of the staff CNMs and the closing of the service. Discussion of the issues is presented, as well as implications for midwifery practice. PMID- 2926517 TI - Managing minor pain in pregnancy. PMID- 2926516 TI - A code of ethics for nurse-midwives: a second proposal. PMID- 2926518 TI - The effect of exercise on the circumvaginal muscles in postpartum women. AB - The effect of exercise on pressure developed by the circumvaginal muscles (CVM) in postpartum women was studied. The CVM assessment system described earlier by Dougherty, Abrams, and McKey used an intravaginal balloon device (IVBD) developed from an impression and model of the vagina. The system (IVBD, pressure transducer and strip chart recorder) provided permanent CVM pressure tracings with high test re-test reliability (n = 16; r = .85) for maximum pressure (MP). The hypothesis in the research reported here was that exercise with and without an IVBD, when compared to no exercise, would result in significantly higher MP and pressure over time (POT). Forty-five healthy PP volunteers were randomly assigned to a 10 minute per day home training program, for six weeks. The baseline and six-week assessments consisted of CVM pressure tracings during contraction. Dependent variables were MP (highest pressure attained) and POT (area under the pressure curve). Although no significant differences were found between the home training groups, greater improvement was found in the exercise groups. Variability within subjects partly accounts for the results. Pressure changes before and after pregnancy and before and after CVM exercise are demonstrated in a case study. The findings support the use of CVM exercise in the postpartum. PMID- 2926520 TI - Antenatal testing, mobile outpatient monitoring service. AB - At Good Samaritan Medical Center in Phoenix, Arizona, a group of perinatal nurses examined the potential for improving care for antepartum, high-risk pregnant women on restricted activities in their homes. An antenatal testing, mobile outpatient monitoring service was developed and implemented within three months. The goal is to reduce frequent admissions to the hospital caused by the interruption of bed rest for weekly and biweekly outpatient evaluation and monitoring. The service has resulted in reduced hospital admissions and improved patient awareness of the need for and adherence to activity restrictions. PMID- 2926521 TI - The perceived attractiveness of preterm infants with cranial molding. AB - A study was conducted to compare the perceived attractiveness of preterm infants with postnatal cranial molding to that of preterm and full-term infants without this deformation. Forty-two subjects who viewed photographs of infants selected preterm infants with postnatal cranial molding as the least attractive group of infants. Researchers have hypothesized that infant appearance is an antecedent to bonding and attachment. Nurses should implement measures such as the use of waterbed mattresses, which have been found to minimize the molding process, and include discussion of this measure when teaching parents about their preterm infants so that they are aware of causes and prevention of cranial molding. If an infant has developed postnatal cranial molding, the parents may require counseling to assist them in resolving their feelings about the discrepancy in the appearance of the infant and what they had anticipated prenatally. PMID- 2926519 TI - The effect of infertility on marriage and self-concept. AB - Two groups of subjects (couples seeking medical treatment for infertility and couples not yet attempting to conceive) completed questionnaires assessing the impact of infertility on their marriages and self-concept. Infertile individuals experienced greater dissatisfaction with themselves and their marriages. Females experienced greater discontent over time and had greater emotional investment than males. Infertile couples, labeled noncommunicators, were found to be affected even more by infertility. Nurses can play vital roles in counseling infertile couples. PMID- 2926522 TI - Health beliefs, health locus of control, and the frequency of practice of breast self-examination in women. AB - The relationship of health beliefs, health locus of control, and the frequency of practice of breast self-examination in women was explored through use of a survey. Health beliefs alone and health beliefs combined with internal health locus of control were found to predict the frequency of practice of breast self examination in a sample of 48 women. The combined variables of health beliefs, internal health locus of control, religion, and occupation explained 80% of the variance in nonpractice and 73.3% of the variance for high practice. Moderate frequency practice was not a significant predictor of breast self-examination. Discriminant function analysis, canonical correlation, and analysis of variance were used in the data analysis. PMID- 2926523 TI - The client's view of hospitalization during pregnancy. AB - The thoughts and feelings expressed by the prenatal hospitalized client are important considerations for care, yet few investigations of this subject have been reported. A qualitative study using descriptive exploratory methods (a questionnaire and tape recorded interview) addressed these questions using a phenomenological approach. The sample comprised 11 women at 26-38 weeks' gestation. Results revealed experiences of loneliness, boredom, and powerlessness. The findings imply that the emotional needs of this particular group may not be met by current nursing interventions. PMID- 2926525 TI - Quantitative versus qualitative research? PMID- 2926524 TI - A national survey about fetal monitoring skills acquired by nursing students in baccalaureate programs. PMID- 2926526 TI - Immunology and infertility. PMID- 2926527 TI - The power of shadows: shadow stereopsis. AB - Our ability to localize objects in three-dimensional space relies primarily on the stereoscopic capability of our visual system. It is generally believed that parallax disparities in the retinal images in our two eyes are required for experiencing stereovision. Traditionally, parallax disparities refer to points that are well defined within the objects, such as edges or boundaries. Shadows can create abrupt luminance changes in the scene but are neither edges nor boundaries, and their position varies with the position of the light sources. It is demonstrated that retinal images with no parallax disparity but with different shadows are fused stereoscopically, imparting depth perception to the imaged scene. Shadows are shown to be an important, hitherto undescribed stereoscopic cue for depth perception. PMID- 2926528 TI - Global spatiochromatic mechanism accounting for luminance variations in contrast sensitivity functions. AB - Psychophysical luminance and chromatic spatial contrast sensitivity functions (CSF's) exhibit a number of variations that depend on the average luminance of the stimulus grating. The contrast sensitivity at each spatial frequency and the maximum resolvable spatial frequency decrease with decreasing average luminance. Most prominently, luminance CSF's have peaks that shift toward lower frequencies, broaden, and disappear as luminance decreases. Chromatic CSF's are flat at low frequencies and do not exhibit luminance-related variations in shape. In this paper, we account for the luminance-dependent variations of CSF's by incorporating them into an earlier model that accounts for the basic high luminance shapes of psychophysical luminance and chromatic spatial CSF's. These variations are modeled by increasing the spatial extent of a global center mechanism while decreasing the inhibitory effect of a global surround on that center. The results support the hypothesis that the global center mechanism changes size as a means of maintaining the dynamic range and controlling the signal-to-noise ratio as luminance varies. PMID- 2926530 TI - How are spatial filters used in fovea and parafovea? AB - The information used in the output of the visual filters was examined for a blur discrimination task for which it had previously been claimed that the best human performance was with pedestal blurs of intermediate magnitude. This conclusion was verified for parameters leading to asymptotic performance for foveal and parafoveal locations. The nature of the computations underlying these visual discriminations was then assessed experimentally and by simulations. The results suggest that a frequency-based model in its simplest form cannot explain these findings. A model based on the spatial properties of filter outputs is discussed. PMID- 2926529 TI - Discrimination of opposite directions measured with stroboscopically illuminated random-dot patterns. AB - The aim of the present experiments was to investigate the maximum displacement over which coherent motion can be perceived (Dmax) for a stroboscopically illuminated moving random-dot pattern, both as a function of the size of the pattern and as a function of the spatial-frequency content. Perception of coherent motion was defined operationally as the ability to discriminate opposite directions. The maximum velocity (Vmax) for which the observer could discriminate the direction of motion for a given strobe rate was obtained by using a forced choice staircase procedure. Vmax was measured as a function of the strobe rate for four different sizes of the pattern. For each pattern size Vmax was limited by the spatial asynchrony between the flashes (Dmax). For a given size of the pattern, Dmax did not depend on the temporal asynchronies tested (10-100 msec). Dmax values were increased with the size of the pattern. Bandpass rectangular filtering was used to change the spatial-frequency content of the pattern. There was a gradual increase in Dmax as the spatial-frequency content shifted to low spatial frequencies. Interestingly, the Dmax that was obtained with the unfiltered pattern was larger than that obtained with the high-pass pattern but also smaller than that obtained with the low-pass pattern. The present results are in agreement with results obtained with a two-frame display. Dmax is not a fixed value: it depends on the size of the pattern as well on the spatial frequency content.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2926531 TI - IgG subclass deficiency in children with recurrent respiratory infections. AB - IgG subclass deficiency frequently occurs in children with recurrent otitis media and respiratory infections. IgG subclasses should be included in the diagnostic evaluation of all such children. PMID- 2926532 TI - Adverse reactions of medical organizations to DTP vaccine: the vaccine-related compensation bill. PMID- 2926533 TI - Sexual history. PMID- 2926534 TI - Chlamydia--screening needs in Oklahoma. PMID- 2926535 TI - Put the patients back. PMID- 2926536 TI - President's page. PMID- 2926537 TI - Stress and the workplace. PMID- 2926539 TI - The path of giants: reflections on teaching clinical medicine. PMID- 2926540 TI - Classification of impacted teeth. PMID- 2926538 TI - Increased lead absorption and lead poisoning from a retained bullet. AB - A young man was found to have elevated blood lead and erythrocyte protoporphyrin levels seven years after he had been shot in the foot with a .22 caliber bullet. Although clearly evident in radiographs obtained at the time of the accident, the bullet had never been removed. Over the course of the intervening years the radiographic appearance of the projectile changed dramatically. The patient underwent a surgical debridement procedure with some resolution of his lead intoxication. This case was reviewed in the context of the literature describing the disposition of retained lead projectiles. Lead bullets or fragments lodged within joints are slowly disintegrated and, as absorption accelerates, predispose the patient to the risk of lead poisoning which may occur many years after the original incident. Prompt removal of any lead projectile entering a joint space is strongly recommended. PMID- 2926542 TI - Maxillary stability following downgraft and/or advancement procedures with stabilization using rigid fixation and porous block hydroxyapatite implants. AB - The stability of results using bone plates for skeletal stabilization and porous block hydroxyapatite implants as a bone graft substitute were evaluated in maxillary downgrafts, maxillary advancements, and modified LeFort III midface advancements. The records of 24 patients with greater than 5 mm of forward or downward movement were evaluated cephalometrically, analyzing the presurgical, immediate postsurgical, and longest follow-up radiographs. The 11 maxillary downgraft, 14 maxillary advancement, and three midface advancement procedures all showed less than 1 mm of relapse. Biopsies of the porous block hydroxyapatite grafts were taken on six patients in this study at 6 to 10 months postsurgery. All showed connective tissue ingrowth and 11.3% to 36.1% bone ingrowth throughout the pores of the implants, and no inflammatory response. PMID- 2926541 TI - Pediatric maxillofacial infections: a retrospective study of 113 patients. AB - This is a retrospective review of 113 hospitalized children with maxillofacial infections. The upper face (orbits, paranasal sinuses, maxillary teeth, and cheeks) was affected most frequently in younger children (mean age = 4.03 years), and the source of infection was often unknown. The patients were treated empirically with a second-generation cephalosporin. Lower-face infections (mandibular teeth, submental, sublingual, and submandibular structures) occurred more frequently in older children (mean age = 5.56 years) and were likely to be of odontogenic origin. Empiric therapy in lower face infections usually consisted of penicillin. PMID- 2926544 TI - Eosinophilic ulcer. AB - A 10-year review of biopsy accessions revealed 15 cases of eosinophilic ulcer. Six manifested recurrent or multiple lesions, and two exhibited histologic atypia. The possible relationships to other oral and systemic diseases are discussed. PMID- 2926543 TI - Psychosocial responses to oral and maxillofacial surgery for head and neck cancer. AB - This study involved extensive interviews with 28 patients who had disfiguring oral and maxillofacial surgery for head and neck cancer. The patients, ages 42 to 76 years, had all been informed of their diagnosis and were in 2- to 5-year postoperative follow-up. Findings pertain to how patients deal with the interpersonal and social ramifications of diagnosis and surgical treatment. Fatalism, delays in help-seeking, responses to diagnosis, postsurgical anxiety, and adjustment were reported. Reassurance prior to surgery was sometimes found to limit understanding of postoperative impairment. Oral and maxillofacial surgeons were seen in heroic or imposing roles that impacted on their capacity to be supportive to patients coping with life change and "handicap." The patient treatment decisions were found to be determined by attitudes about death, which motivated patients and surgeons to make difficult or extreme choices. Suffering, social changes, and postoperative uncertainty were patient concerns. Patient strategies for adjusting to disfiguration are examined, and specific recommendations for the oral and maxillofacial surgeon are made. PMID- 2926545 TI - Arthroscopic treatment of anterior disc displacement: a preliminary report. AB - A new suturing technique for stabilizing anteriorly displaced discs that have been reduced arthroscopically after removal of adhesions, lateral pterygoid release, and stretching the lateral capsule is presented. This procedure has provided successful results, although the evaluation is only short-term. No complications have occurred using this suturing technique. PMID- 2926547 TI - Chronic preauricular swelling. PMID- 2926546 TI - Comparison between the peripheral ossifying fibroma and peripheral odontogenic fibroma. AB - This study presents previously unreported data on a series of 400 peripheral ossifying fibromas (POFs) and 13 peripheral odontogenic fibromas (PODFs). The differences between the two lesions are discussed, and comparisons are made with other reports in the literature. It is concluded that the lesions represent separate pathologic entities. PMID- 2926548 TI - Verruciform xanthoma within carcinoma in situ. AB - This report describes an unusual case of verruciform xanthoma of the posterior floor of the mouth that occurred within carcinoma in situ. The significance of this case is described in light of current theories on the etiology and management of verruciform xanthoma. PMID- 2926549 TI - Ectopic apocrine cyst in the facial area. AB - An unusual cyst of the facial area that histologically demonstrated apocrine differentiation in its lining is described. Its etiology could not be determined. PMID- 2926550 TI - Fibroma-like lesion arising in the temporal region. PMID- 2926551 TI - Pharyngeal perforation during intubation in a patient with Crohn's disease. AB - A case of pharyngeal perforation in a patient with Crohn's disease is described. Crohn's disease may complicate intubation either because of oral lesions changing the local soft tissue architecture, or because chronic corticosteroid therapy has lessened tissue resistance to perforation. Consideration may be given to adjunctive measures when intubating patients with a history of Crohn's disease. PMID- 2926552 TI - Small round cell neoplasm of jaw in a patient with medulloblastoma. AB - A 24-year-old woman presented with a painful mandibular swelling 6 months after multimodality treatment for a cerebellar medulloblastoma. The tumor was microscopically identical to the cranial neoplasm and a part of widespread dissemination as determined by ancillary studies. Previous concepts of the nonmetastasizing nature of intracranial neuroectodermal neoplasms have been modified by studies on treated cases, surgery being considered a virtual prerequisite for this occurrence. Extracranial neoplastic development of a PNET of CNS origin must be considered in disease-free treated patients up to several years after initial therapy. PMID- 2926553 TI - Synovial chondromatosis of the temporomandibular joint diagnosed by magnetic resonance imaging: report of a case. AB - A case of synovial chondromatosis of the temporomandibular joint with extracapsular extension is described. Temporomandibular joint magnetic resonance imaging proved invaluable in establishing a definitive diagnosis. PMID- 2926554 TI - Rhabdomyosarcoma of the parapharyngeal space in an adult patient: an immunohistochemical study. AB - Rhabdomyogenic malignancies occasionally challenge the diagnostic acumen of many pathologists. The diverse histologic patterns of RMS can range from the somewhat undifferentiated primitive to the bizarre, pleomorphic varieties. These neoplasms can be highly lethal and, until recently, were resistant to even the most aggressive surgical management. The grave prognosis for patients with RMS has remarkably improved however, as a result of careful clinical staging, awareness of histologic features and immunohistochemical techniques for identification, newer techniques in defining the extent of the disease, and multimodal therapy consisting of surgery, radiation, and chemotherapy. Immunohistochemical methods with specific antibodies, as used in this case, have proved to be the only definitive method to identify this variant subclass of RMS. PMID- 2926555 TI - Technical considerations in mandibular ridge reconstruction with collagen/hydroxylapatite implants. AB - A surgical technique for placement of a collagen-hydroxylapatite implant to augment severely atrophic mandibles is described. PMID- 2926556 TI - Modified sagittal split technique for patients with a high lingula. AB - Unfavorable fractures of the proximal fragment during the sagittal ramus split procedure, although uncommon, occur with an incidence ranging between 3% and 6.6%. One anatomic feature that may predispose to an unfavorable fracture is a thin mandibular ramus in the region of the medial osteotomy. One particular situation that can increase the risk of an unfavorable fracture is a lingula that is situated very high on the mandibular ramus. Even in a normal-sized mandibular ramus, a high lingula places the medial cut in a thin region where there is little or no cancellous bone. The technique presented is a modification of the sagittal split osteotomy which can assist the surgeon in preventing an unfavorable fracture should an unusually high lingula or a thin ramus be encountered. PMID- 2926557 TI - The nurse with a central line--when the patient is you. AB - The nurse who lives with a central line has a unique perspective. She is able to relate to both nurses and patients in a very special way. This article discusses the concerns and experiences of a nurse who has lived with a central line for over five years. The goal of the article is to assist nurses as they care for patients with central lines. PMID- 2926558 TI - A study of pain management: patient controlled analgesia versus intramuscular analgesia. AB - A clinical study examining the efficacy of Patient Controlled Analgesia compared with Intramuscular Analgesia was conducted. Patient Controlled Analgesia (PCA) Therapy was used in a select group of patients after major abdominal surgery. Specific parameters monitored were: total amount of analgesia required, incidence of pulmonary complications, assessment of pain level and sedation, patient activity, nursing time required for administration, safety, cost-effectiveness of both modes of analgesia and length of hospital stay. A questionnaire survey of both patients and nursing staff was done to evaluate responses. Conventional pain management often is inadequate with PRN administration of analgesic drugs due to the unpredictable and uneven patient absorption rate and the individual pain intensity and tolerance. The patient experiences a repetitive cycle of pain and sedation. The patient on PCA therapy is able to titrate his analgesic medication very effectively and maintain a state of analgesia without sedation. He is more responsive and able to participate in the early postoperative rehabilitation phase. The transition to oral medication usually was accomplished at 48 hours postoperative. PMID- 2926559 TI - Who will pay for intercalated degrees in pathology? PMID- 2926560 TI - Castleman's disease: the plot thickens. PMID- 2926561 TI - Expression of the nuclear oncogene p53 in colon tumours. AB - The nuclear tumour antigen p53 is expressed by a gene localized on the p-arm of human chromosome 17, a region frequently deleted in colon carcinomas. Using a monoclonal antibody to p53 antigen, immunohistochemical analysis of carcinomas and dysplastic tubular adenomas of the colon has been performed to study the relation between p53 expression and dysplasia or malignancy. With this methods p53 was detectable in 55 per cent of colon carcinomas (n = 29). In 8 per cent of adenomas (n = 74), focal nuclear p53 expression was found in dysplastic epithelial cells. In general, these p53-positive regions of the polyps were histologically indistinguishable from the neighbouring tubuli. Sometimes the p53 positive nuclei were found in a focus of more highly dysplastic epithelium. The results suggest that expression of the p53 gene may be part of the process of malignant transformation of dysplastic colon polyps. PMID- 2926563 TI - Contact relationships between vascular smooth muscle cells: an in vivo and in vitro study. AB - Cell/cell contacts in the intact media of the rat thoracic aorta and inferior vena cava, and in cultured smooth muscle cells from these vessels have been quantified in order to determine whether their density and their type can be correlated with the differences in load at these two sites. The type and number of contacts per 100 microns of cell perimeter and per 100 cells were determined with a semi-automatic image analysis system. In all cases there was a predominance of simple appositions; intermediate junctions, interdigitations, and nexus junctions were less frequently observed. There were more cell contacts of each type in the intact arteries than in the intact veins. In cell cultures, all types of cell contacts were increased but the proportion of load bearing types was reduced. PMID- 2926564 TI - Enterochromaffin-like cell populations in human fundic mucosa: quantitative studies of their variations with age, sex, and plasma gastrin levels. AB - The human gastric fundal mucosa contains a variety of endocrine cells, the most numerous of which are the so-called enterochromaffin-like (ECL) cells. We have studied the variations with age and sex of the ECL cell populations, utilizing an assessment based on multiple endoscopic biopsies from four groups of subjects. Plasma gastrin levels were also determined in these subjects. In males, endocrine cell densities declined with age but the ECL cell numbers in females opposed this trend. ECL cell counts showed no appreciable differences between young and old females. In older females, there was a high rate of gastritis and increased levels of circulating gastrin. Concentrations in older females (29.6 +/- 8.7 pmol/l) were higher than in both younger (less than 45 years) males (5.3 +/- 1.1 pmol/l) and older (greater than 55 years) males (6.3 +/- 0.6 pmol/l) (P less than 0.05). The plasma gastrin level was also higher in older females than in young females (13.1 +/- 4.5 pmol/l), although this difference failed to reach statistical significance. In conclusion, clinically silent gastritis, raised gastrin levels, and maintenance or rise of ECL cells numbers, in opposition to a general decrease in endocrine cells with age, appear to be features of women of more than 55 years of age. The variations in ECL cell populations reported here should be taken into account when evaluating possible pathological alterations of the stomach. PMID- 2926565 TI - Macrophages in bronchoalveolar lavage fluid are not representative of macrophages in granulomas of the lungs of BCG-infected mice. AB - To find out whether macrophages obtained by bronchoalveolar lavage (BAL) represent the macrophage population in alveoli, we performed a quantitative study to compare the expression of cell-surface antigens by macrophages in the lavage fluid as well as in the alveolar spaces of sectioned lung tissue from normal and BCG-infected mice. The amount of antigen on cells, determined with a quantitative immunocytochemical method, was expressed as the mean specific absorbance per 0.25 micron2 cell-surface area. In normal mice, BAL and intra-alveolar macrophages are identical. Macrophages in BAL fluid and intra-alveolar macrophages, both from BCG infected mice, expressed antigen F4/80 and Fc receptor II to about the same extent, but the former showed a significantly higher level of antigen expression as defined by antibodies M1/70, M5/114, 30.G.12, and M3/38. In granulomatous lesions, expression of antigens by macrophages, assessed semi-quantitatively, was considerably less than that by BAL macrophages. Lymphocytes in the BAL fluid resembled those in the granulomas. These findings led to the conclusion that in BCG-infected mice, the macrophages found in BAL fluid do not resemble those occurring in either the alveoli or the granulomatous lesions of the lungs. On these grounds, the relevance of findings in BAL fluid to lung interstitial lung diseases should be reconsidered. PMID- 2926562 TI - The relationship between the distribution of lymphoid cells in the skin and in vitro adhesion to connective tissue. AB - An in vitro assay was used to test whether the patterns of lymphocyte distribution in the mouse skin could be explained by adhesion of lymphoid cells to connective tissue. Using normal skin as a substrate, in vitro adhesion was significantly greater below the panniculus carnosus muscle: when oxazolone sensitized skin was used, binding was seen throughout the skin. This correlated closely with the patterns seen in vivo following injection of lymphocytes into normal skin or sensitization with oxazolone. Adhesion was not affected by divalent cation chelating agents, but was reduced in the presence of some monosaccharides. The property of skin adhesion did not appear to be confined to a small number of cells in the spleen cell preparation. Although only a small proportion of the starting population adhered to the section, transfer of the non adherent cells to a fresh skin section produced a similar degree of adhesion. It is suggested that the variable binding of lymphoid cells by skin connective tissue may be an important factor in determining the retention of cells which have emigrated into the skin from the blood vessels and may explain the distinctive patterns of distribution of lymphocytes in cutaneous inflammatory disorders. PMID- 2926566 TI - How do we teach pathology? Pathology teaching at Southampton. PMID- 2926568 TI - Sudden infant death syndrome and birth weight. AB - We studied 2962 cases of sudden infant death syndrome (SIDS), derived from linked birth and death records, to specify further the descriptive epidemiologic data on recognized SIDS risk factors and to examine interrelationships among multiple risk factors and SIDS while controlling for the influence of birth weight (using logistic regression). The results generally confirmed those of other studies, with the exception of a higher incidence of SIDS among Chinese and Japanese babies and a lower incidence among Hispanic babies, all in comparison with white, non-Spanish (Anglo) infants. Median age at death was found to vary by birth weight, with very low birth weight babies being about 6 weeks older (postnatal age) than normal birth weight babies at time of death. The association of the risk factors with SIDS remained when birth weight data were statistically controlled; the association of these risk factors with SIDS cannot be explained by their relationship to birth weight. An interaction was found between race and maternal age and between multiparity and type of hospital of birth. There was no interaction between birth weight and the other risk factors. PMID- 2926569 TI - Injury hazards in home day care. PMID- 2926567 TI - Use of subcutaneous recombinant human erythropoietin in children undergoing continuous cycling peritoneal dialysis. AB - Five anemic, transfusion-dependent patients aged 12 to 18 years, who had end stage renal disease (mean hematocrit value 22 +/- 0.31%) and were on a regimen of peritoneal dialysis, were treated with recombinant human erythropoietin (rHuEpo), which was self-administered at home by subcutaneous injections thrice weekly at an initial dosage of 150 U/kg. All patients had an increase in the reticulocyte count and hemoglobin concentration, and none required further transfusions. The hematocrit level rose to a mean of 33.04 +/- 1.86% within 3 weeks of rHuEpo therapy, and the dosage was adjusted to keep the hematocrit level between 32% and 38% indefinitely. Currently four of these patients require only one dose a week to sustain the hematocrit level. No antibodies to the rHuEpo were formed. Three patients had an exacerbation of hypertension, which required an adjustment in antihypertensive therapy. No other side effects were noted. The results demonstrate that rHuEpo is effective in correcting the anemia of end-stage renal disease, thereby eliminating the associated clinical symptoms and the need for further blood transfusions. PMID- 2926570 TI - Scaling skin in the neonate: a clue to the early diagnosis of X-linked hypohidrotic ectodermal dysplasia (Christ-Siemens-Touraine syndrome). The Executive and Scientific Advisory Boards of the National Foundation for Ectodermal Dysplasias, Mascoutah, Illinois. PMID- 2926571 TI - Late neonatal vitamin K deficiency associated with subclinical liver dysfunction in human milk-fed infants. PMID- 2926572 TI - Atypical presentation of Kawasaki disease with early development of giant coronary artery aneurysms. PMID- 2926573 TI - Succinic semialdehyde dehydrogenase deficiency associated with combined 4 hydroxybutyric and dicarboxylic acidurias: potential for clinical misdiagnosis based on urinary organic acid profiling. PMID- 2926574 TI - Posthemorrhagic hydrocephalus in high-risk preterm infants: natural history, management, and long-term outcome. AB - The natural history, medical management, and outcome in infants with progressive posthemorrhagic hydrocephalus after intraventricular hemorrhage were studied prospectively. Infants with asymptomatic severe posthemorrhagic hydrocephalus were managed with a predetermined protocol. Outcome between groups at 1 to 2 years and at more than 3 years was compared. The natural history study, restricted to the inborn population, revealed that posthemorrhagic hydrocephalus developed in 53 of 409 infants with intraventricular hemorrhage. The progression of hydrocephalus either was arrested or regressed in 35 of 53 infants; progression to severe hydrocephalus occurred in 18 of 53 infants. The severe posthemorrhagic hydrocephalus was asymptomatic in 16 of 18 infants. The management and outcome study included both inborn and outborn infants. Of 50 infants, 12 had symptomatic severe hydrocephalus and 38 had asymptomatic severe hydrocephalus. The 16 infants managed with close observation were as likely to remain shunt free as the 22 infants managed with serial lumbar punctures. Of 38 infants, 20 were managed without shunts. At 3 to 6 years, the outcome of infants in the close observation group did not differ from that in the lumbar puncture group. Long-term outcome of infants with progression to asymptomatic severe hydrocephalus did not differ from that of infants in whom disease progression was arrested. Poor outcome in infants with intraventricular hemorrhage and subsequent posthemorrhagic hydrocephalus was related to severity of hemorrhage and gestational age at birth less than 30 weeks. Because long-term outcome of infants with severe hydrocephalus did not differ from that of infants in whom the progression of hydrocephalus was arrested or whose condition improved before hydrocephalus became severe, we currently attempt medical management of these infants. PMID- 2926575 TI - Effect of spironolactone-hydrochlorothiazide on lung function in infants with chronic bronchopulmonary dysplasia. AB - To test the hypothesis that spironolactone-hydrochlorothiazide (Aldactazide) will improve urine output and lung function in infants with bronchopulmonary dysplasia, we studied 21 hospitalized, spontaneously breathing, oxygen-dependent infants with chronic bronchopulmonary dysplasia. Infants were randomly assigned to receive either a 1:1 mixture of spironolactone and hydrochlorothiazide orally (n = 12) (3 mg/kg/day of both compounds) or no treatment (n = 9) for 6 to 8 days each. Dynamic lung compliance, total pulmonary resistance, and hemoglobin oxygen saturation were measured on the first and last days of each study period. Fluid intake and urine output were measured each day. Although the treatment significantly increased urine output, neither lung mechanics nor oxygenation were improved by the drug. The magnitude of the diuresis achieved with spironolactone hydrochlorothiazide treatment was comparable to the diuresis achieved in a previous study of furosemide treatment (J Pediatr 1986:109;1034-9). Statistical analysis indicated that a type II error was an unlikely explanation for our failure to detect a beneficial effect. In three patients, doubling the oral dose did not improve lung mechanics or oxygenation. We speculate that diuresis per se is not responsible for lung function improvement during treatment with other drugs with diuretic properties. PMID- 2926576 TI - A comparative study of cardiac output in neonates supported by mechanical ventilation: measurement with thoracic electrical bioimpedance and pulsed Doppler ultrasound. AB - In newborn infants supported by mechanical ventilation, cardiac output was measured simultaneously with thoracic electrical bioimpedance and pulsed Doppler ultrasound to determine whether the impedance technique is reliable and accurate in this age group. The mean difference between paired measurements with the two techniques in 26 subjects was negligible (less than 1 ml/kg/min), with 95% confidence limits being approximately 11% of the mean Doppler-derived cardiac output. In addition, the two techniques related well (correlation coefficient r = 0.94) over a wide range of Doppler-derived cardiac output measurements (120 to 530 ml/kg/min). In 8 of the 26 subjects, cardiac output was observed for 7 to 12 hours. The mean difference between the Doppler and impedance techniques was 6.1% to -0.7% of the Doppler value. Thoracic electrical bioimpedance is applicable to newborn infants and offers a continuous noninvasive method of cardiac output measurement. PMID- 2926577 TI - Lorazepam pharmacodynamics and pharmacokinetics in children. AB - We evaluated the effects of low doses of lorazepam on episodic versus long-term memory, attention, and somatic and affective symptoms, as well as its pharmacokinetics, in a group of 16 children aged 2.8 to 14.2 years. Psychologic assessments of each child were performed twice before intravenous administration of lorazepam (0.03 mg/kg), and 1 1/2 hours and 24 hours after lorazepam; there were no significant changes in long-term memory, attention, or somatic symptoms. There was a significant decrease in affective symptoms at 1 1/2 hours (p = 0.011), with a trend toward decreased anxiety at 1 1/2 and 24 hours after lorazepam (p = 0.026 and 0.028, respectively). There was also a selective anterograde amnestic effect in 5 of 16 children after lorazepam (p = 0.06). Mean (+/- SD) lorazepam systemic clearance was 1.3 +/- 0.4 ml/min/kg, with a terminal half-life of 10.5 +/- 2.9 hours and an unbound clearance of 15.9 +/- 5.2 ml/min/kg. A group of healthy adult volunteers who were given lorazepam had a mean systemic clearance of 1.0 +/- 0.4 ml/min/kg, somewhat less than that of the children (p = 0.069). There were no significant differences in any lorazepam pharmacokinetic parameter between those children who did versus those who did not have changes in affective symptoms or amnesia. These data should be helpful in establishing the dose of lorazepam in children, as the drug becomes more widely used as an antiemetic, premedicant, and anticonvulsant agent. PMID- 2926579 TI - Immediate adverse reactions to acetaminophen in children: evaluation of histamine release and spirometry. PMID- 2926578 TI - Pharmacokinetics of N-desmethylmethsuximide in pediatric patients. PMID- 2926580 TI - Just Say No. PMID- 2926581 TI - Prevention of adolescent drug abuse: why "Just Say No" just won't work. PMID- 2926582 TI - Prophylactic agents in the prevention of periventricular hemorrhage. PMID- 2926583 TI - Teratogenic effects of anticonvulsant drugs. PMID- 2926584 TI - Treatment of nocturnal enuresis. Proceedings of a symposium. August 6, 1988. PMID- 2926585 TI - Nocturnal enuresis: an approach to treatment based on pathogenesis. PMID- 2926586 TI - Nocturnal enuresis: experience with long-term use of intranasally administered desmopressin. PMID- 2926587 TI - Factors influencing lethality of Bacillus thuringiensis kurstaki toxin for eggs and larvae of Trichostrongylus colubriformis (Nematoda). AB - A toxin from Bacillus thuringiensis kurstaki was lethal to eggs and first- and second-stage larvae of the ruminant nematode Trichostrongylus colubriformis. Sheathed and exsheathed third-stage larvae were also killed by the toxin. However, susceptibility of the ova to the toxin decreased after several hours of development. Heating at 65 C for 1 hr or freezing at 0 C for 3 mo did not affect stability of the toxin. Ovicidal activity of the toxin was not altered by treatment with 13 microbial or mammalian enzymes, but toxicity was reduced by the antibiotics streptomycin or penicillin G and the enzyme inhibitor L-1-tosylamide 2-phenylethylchloromethyl ketone. Cuprous, ferrous, and zinc chlorides also inhibited the ovicidal activity of the toxin. Increased osmolarity of the assay media or solubilization of the toxin from pH 3 to 11 had no effect on toxicity for eggs. The membrane agents sodium vanadate and 4,4'-diisothiocyano-2,2' disulfonic acid stilbene increased (9-fold) and decreased (333-fold) toxicity, respectively. N-acetylneuraminic acid was the only tested sugar that reduced the toxicity of B. t. kurstaki. PMID- 2926588 TI - The phylogenetic status of the Ancyrocephalidae Bychowsky, 1937 (Monogenea: Dactylogyroidea). AB - Phylogenetic analysis of selected subfamily and family taxa within the Dactylogyroidea indicates that the Ancyrocephalidae Bychowsky, 1937, is unnatural. The family contains both poly- and paraphyletic features. The analysis supports the previous elevation of the Pseudomurraytrematinae to family status and suggests that revision of the Ancyrocephalidae is necessary. Two options for revision are provided; that of returning the taxon to subfamily status within the Dactylogyridae is preferred, requiring a change in status of the Heterotesiidae to a subfamily within the Dactylogyridae. PMID- 2926589 TI - Eimeria cryptotis n. sp. (Apicomplexa: Eimeriidae) from the least shrew, Cryptotis parva (Insectivora: Soricidae), in north-central Texas. AB - From March through November 1987, 14 least shrews, Cryptotis parva (Say), were collected in portions of north-central Texas and examined for coccidian parasites; only 1 (7.1%) was found to be passing oocysts. Eimeria cryptotis n. sp. is described herein as new and represents the only coccidian reported thus far from C. parva. Sporulated oocysts are subspherical, 16.4 x 15.3 (14-18 x 13 17) microns; shape index 1.1 (1.0-1.2) microns. A micropyle and oocyst residuum are absent, but a polar granule is present. The sporocysts are ovoid, 10.6 x 7.0 (9-11 x 6-8) microns; shape index 1.5 (1.4-1.8) microns. Stieda and substieda bodies and a sporocyst residuum are present. The sporozoites are elongate and only 2 could be observed well enough to measure (11.2 x 2.4 and 8.8 x 2.4 microns) because they are normally obscured by the sporocyst residuum. Sporozoites lack refractile bodies and contain a centrally located nucleus. The new species can be distinguished from the majority of insectivore coccidia on the basis of oocyst size. PMID- 2926590 TI - Australiformis semoni (Linstow, 1898) n. gen., n. comb. (Acanthocephala: Moniliformidae) from marsupials of Australia and New Guinea. AB - Australiformis n. gen. is erected for Echinorhynchus (Gigantorhynchus) semoni Linstow, 1898, from Australian and New Guinea marsupials. The new genus differs from Moniliformis and Promoniliformis in lacking spiral muscles in the outer wall of the proboscis receptacle. Linstow's species, E. semoni, is redescribed from abundant material from Peramelidae and Dasyuridae from Australia and New Guinea. PMID- 2926591 TI - Trypanosoma (Herpetosoma) leeuwenhoeki in Choloepus hoffmanni and Didelphis marsupialis of the Pacific Coast of Colombia. AB - Trypanosoma (Herpetosoma) leeuwenhoeki, originally described in Panamanian sloths, was isolated from Didelphis marsupialis (Marsupialia) and Choloepus hoffmanni (Edentata) inhabiting the Pacific coast of Colombia. Trypanosomes were characterized by their large blood forms (total length 51-53 microns), poor infectivity for mice, and lack of development in Rhodnius prolixus. Isoenzyme studies, with either strains or clones, revealed homogeneous profiles clearly distinct from Trypanosoma cruzi and Trypanosoma rangeli reference strains. The present report extends the geographical distribution of T. leeuwenhoeki to South America and broadens its known host range to another order of mammals. PMID- 2926592 TI - Helminth communities in avocets: importance of the compound community. AB - This paper reports patterns of similarity and overlap in species presence and patterns of linear distribution of intestinal helminths in 22 avocets from 4 populations. Avocets collected from ephemeral bodies of water in Alberta and Manitoba had communities composed largely of species that are avocet specialists plus some that are host generalists. The composition of helminth communities in these hosts was similar to that reported in earlier surveys of avocet helminths. There was little evidence for competition between helminth species in these communities. In contrast, avocets collected from permanent bodies of water in Alberta had communities composed largely of species that are specialists in various duck species, particularly lesser scaup. These helminths were superimposed on the normal community, fitting into linear gaps along the intestine but also overlapping the distributions of avocet specialists. These lesser scaup specialists exhibit interactive patterns amongst themselves and, to some extent, with avocet specialists. Helminth communities in avocets from ephemeral bodies of water have vacant niches and are largely isolationist in nature. Those in avocets from permanent bodies of water are saturated and are more interactive in nature. PMID- 2926593 TI - Phagocytic activity of hemocytes of M-line Biomphalaria glabrata snails: effect of exposure to the trematode Echinostoma paraensei. AB - The phagocytic activity of hemocytes from 6-8-mm M-line Biomphalaria glabrata snails was studied in an in vitro assay using glutaraldehyde-fixed sheep erythrocytes (SRBC) as target cells. For individual snails, the percentage of hemocytes ingesting SRBC during a 1-hr interval, termed the phagocytic activity index (PAI), was determined. Hemocytes from snails infected for 1 day with Echinostoma paraensei had a slightly elevated PAI, but at both 8 and 30 days postexposure (DPE), hemocytes from infected snails had a significantly lower PAI than controls. Hemocytes taken from snails at 8 DPE also had a low PAI using rabbit erythrocytes and yeast as target cells. The low PAI at 8 DPE is attributed to the presence of large numbers of poorly spreading hemocytes with low phagocytic activity. Hemocytes from snails with 30-day infections were well spread but nonetheless had a low PAI. The presence of plasma from 8-day infected snails did not alter the PAI of hemocytes from control snails, nor was the PAI of hemocytes from infected snails changed by plasma from control snails. SRBC preincubated for 60 min in plasma from various groups of M-line snails did not elicit an increase in PAI when presented to hemocytes from control snails; in some cases, as with plasma from 6-8-mm control snails, such preincubation significantly reduced the PAI below levels obtained using SRBC preincubated in culture medium. As compared to hemocytes from snails with normally developing, 8 day-old intraventricular sporocysts (IS), hemocytes from snails exposed to infection but subsequently lacking IS had a significantly higher PAI.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2926594 TI - Ultrastructural study of the host-parasite interface of Moniliformis moniliformis (Archiacanthocephala) in laboratory-infected rats. AB - The fine structure of the host-parasite interface of Moniliformis moniliformis in rats is described, comprising investigations on the ontogenic development of the presomal tegument, on the lesions caused by the worms, and on the host cellular reactions at the points of attachment of the worm. The presomal tegument of the worm contained more fibrous elements than the metasomal tegument. The sclerotization increased with the ages of the worms and toward the tip of the proboscis. The presomal surface coat was more coarsely structured and osmiophilic than that of the metasoma and was neither continuous with the contents of the tegumental crypts nor supported by lipids from necrotic host tissue. The surface coat occasionally detached from the proboscis, probably due to the activity of the surrounding granulocytes of the host. The proboscis hooks lost their tegumental covering during their larval development. Hooks of all worms from rats were invested with a semiliquid lipid coat, apparently derived from tegumental excretions at the base of the hooks. The invaginated area of excretion around the base of the hooks was rich in endoplasmic reticulum. The hooks seemed to renew their lipid coats at certain intervals by dipping into the excreted lipid. In rats all worms, irrespective of their age, attached superficially, penetrating only the intestinal mucosa and the tunica propria. No fibrous connective tissue was found in the lesions caused by the worms, indicating that they frequently changed their site of attachment. At 3-10 days postinfection the host's defense cells observed in the lesions consisted mainly of granulocytes, whereas plasma cells were the predominant leukocytes in lesions of older infections. PMID- 2926595 TI - Fine structure of anterior terminus of apical sense organ in Macracanthorhynchus hirudinaceus (Acanthocephala). AB - The apex of the proboscis of Macracanthorhynchus hirudinaceus is crowned by a cone-shaped projection with a small opening in its center. The bottom of this opening is the anterior terminus of the apical sensory organ. When viewed in transverse section, the anterior terminus of this organ appears as a series of distinct layers that encircle a central cone enclosing a complex arrangement of nerves and a sensory support cell duct. Four membrane-defined layers encircle the cone area. The outermost glycocalyx is morphologically identical with that described on the metasoma. The second layer, or tegument, is similar in appearance to that observed on the trunk except for the greater abundance of keratinlike bundles throughout. These bundles are also organized into a loose network along the inner tegumental membrane. The third layer, a latticework of fine filaments containing few organelles, has an erratic boundary that occasionally extends into layer 4. The area adjacent to the inner and outer boundary contains numerous vesicles. Layer 4 has 2 distinct zones. The outer contains filaments arranged as in circular muscle; whereas, the medial lacks such filaments but consists of a finely grained matrix. Radiating throughout both zones are numerous osmiophilic bundles of fibers. The cone at this level contains 8 branches of the apical sensory nerves that interdigitate with the duct from the sensory support cell. Numerous filaments and vesicles are associated with this complex. PMID- 2926596 TI - Alterations in Ascaris suum larval burdens, eosinophil numbers, and lysophospholipase activity associated with low levels of dietary iron. AB - The effect of various amounts of dietary iron on the immune response was investigated using BALB/cAnNCr/BR mice infected with Ascaris suum. Changes in numbers of larvae, numbers of eosinophils, and levels of lysophospholipase (LPL) activity in lung or liver tissues were analyzed from nonimmune and immunized mice at 2 and 7 days postinfection (PI). Various iron diets did not influence the numbers of tissue larvae, eosinophils, or the LPL activity in lungs or livers of nonimmunized mice at various times after infection. Lung and liver LPL activity was reduced in immunized mice without significant changes in larval numbers at 2 days PI. At 7 days PI, lung and liver LPL activity, eosinophil numbers, and numbers of larvae were increased in immunized mice receiving low iron diets. Results confirm that low iron diets affect the host response to A. suum. PMID- 2926597 TI - Isolation of free-living amoebas from the intestinal contents of reptiles. AB - A total of 508 reptiles captured at Canary Islands (Spain) was examined for free living amoebas. Two hundred seventy-three clones of amoebas were isolated by culture of gut contents, 157 of them belonging to the genus Acanthamoeba and 12 to the genus Naegleria. PMID- 2926598 TI - A novel method for cloning Eimeria praecox in the chicken. AB - A new method for producing clones of Eimeria praecox by infection of chickens with a single sporozoite retained within a sporocyst is described. PMID- 2926599 TI - Alaria nasuae (Trematoda: Diplostomidae) from domestic dogs. AB - Two stray dogs were found naturally infected with adult Alaria nasuae in Tamaulipas, Mexico. This is the first report of this species from a domestic dog, the first report of it from Mexico, and the first time the species has been recorded since its original description. PMID- 2926600 TI - Effects of Schistosoma mansoni on the nutrition of its intermediate host, Biomphalaria glabrata. AB - Biomphalaria glabrata infected with Schistosoma mansoni and maintained on an artificial diet of Spirulina alga displayed reduced growth during the 5 wk following patency. Food consumption per unit snail weight was unaffected. Infected snails also failed to lay eggs. No difference in percentage of assimilation was observed between control and infected individuals, but infected snails had significantly decreased gross conversion efficiencies. The effects of infection on nutrition of B. glabrata were similar to those observed in nutrient deprived snails fed diets containing low Spirulina levels. Nutrient deprivation, however, did not alter conversion efficiency. PMID- 2926602 TI - Particulate content of large volume parenteral solutions. PMID- 2926603 TI - Validation of an automated filter integrity tester for use in bubble point testing. AB - The basic principles of filter integrity testing (bubble point test) are explained. An automatic filter integrity testing machine was validated by challenging the unit's ability to differentiate between integral (intact) and nonintegral filters using a manual method as a standard. PMID- 2926601 TI - The recovery of highly purified biopharmaceuticals from perfusion cell culture bioreactors. AB - The impact of continuous perfusion cell culture technology on production of one and two chain human rtPA, as well as monoclonal IgG and IgM, will be reviewed. Perfusion as compared to batch systems improve the quality of the product in the conditioned media in terms of biological activity and structural integrity. This significantly increases downstream recovery and daily production output of final purified material. These findings are a consequence of the ability of perfusion technology to 1) maintain cells intact at high cell density; 2) effectively reduce serum content to approximate serum free conditions; and 3) minimize residency time of labile product within the 37 degrees C environment of the bioreactor. PMID- 2926604 TI - Method evaluation: automated microscopy as a compendial test for particulates in parenteral solutions. AB - Accurate enumeration and sizing of contaminant particles in parenteral solutions are critical to the assessment of product quality and suitability for patient use. Current manual microscopic and instrumental (light obscuration) methodologies specified by the USP both result in data of high variability. The microscopic assay for large volume parenterals is time consuming and incorporates an undesirable level of subjectivity; light obscuration counters tend to undersize larger particles and fibers and have low detection efficiency for some particle types commonly present in small volume injections. Light microscopic image analysis is proposed as a method which combines the best features of the two present methods and allows an accurate, precise, and cost effective analysis of parenteral contaminant particles. This paper briefly summarizes the principles of microscopic image analysis and discusses its application in concert with optimized sampling and counting techniques as an improved compendial methodology. Instrument performance requirements are discussed with reference to a number of currently available image analysis systems. PMID- 2926605 TI - Current regulatory issues regarding parenteral inspections. PMID- 2926606 TI - Acceleration of heat transfer in vial freeze-drying of pharmaceuticals. I: Corrugated aluminum quilt. AB - The medium offering the greatest resistance to heat transfer from the freeze dryer shelf to the moving and subliming interface within the product is the space between the flat shelf top and the concave vial bottom. The resistance to heat transfer can be greatly reduced by improving the thermal conductivity of this intervening space. Several heat transfer augmentation devices, which fill this gap, are described. The devices are inexpensive and easy to use. Experimental data show that the resistance of the intervening space is reduced appreciably and the drying time is greatly reduced. PMID- 2926607 TI - Anorexia nervosa. PMID- 2926608 TI - Responding to your feedback. PMID- 2926609 TI - Lyme disease: an elusive diagnosis. AB - Lyme disease presents health care practitioners with a complex set of challenges. The history, physical assessment, and clinical evaluation must all be meticulously performed, as Lyme disease can prove to be an exceptionally elusive entity. This article details the pathogenesis, clinical manifestations, nursing history, and health care implications of Lyme disease. Education is emphasized as the key to both the detection and prevention of this rapidly increasing syndrome. PMID- 2926610 TI - Infantile apnea monitoring and SIDS. AB - Primary care practitioners are presented with many concerns and questions from families about Sudden Infant Death Syndrome (SIDS), apnea, and monitors. Clinicians need to know which symptoms are of concern, when to ask for consultation from an apnea center, and how to refer the parent for support and counseling. This article reviews the current knowledge of infantile apnea, monitoring, and SIDS. An approach to evaluation and management is presented. PMID- 2926611 TI - Future potential, phase I: nurse practitioners look at themselves. AB - Nurse practitioners identified as successful were interviewed to evaluate factors related to the viability of nurse practitioners in the health care system. The interviewees believed they were successful because they provided a nursing dimension of primary care, developed strategies to market themselves and their services, collaborated with physicians who saw them as colleagues, and had certain personality characteristics. In addition, the interviewees suggested strategies to enhance practice and potential nurse practitioner roles. These results suggest further research in two areas: investigation of health care administrators and management to solicit their ideas about the future strategic issues for the development of nurse practitioner roles and a broader, more formal survey of nurse practitioners regarding their success in the marketplace. PMID- 2926612 TI - Pediatric nurse practitioners develop ambulatory surgery cardiac program. AB - The major objective for the Pediatric Cardiac Day Surgery Program at Children's Medical Center of Dallas is to promote cost-effectiveness while the quality of physical and psychosocial preparation of the child having cardiac surgery is maintained. The pediatric patients have comprehensive preoperative workups and teaching provided by pediatric nurse practitioners. The unique knowledge base, expertise, and clinical skills of the pediatric nurse practitioner have enabled the program not only to succeed but also to pave the way for the utilization of the Day Surgery Unit by many other surgical services. PMID- 2926613 TI - Testing some attribution-emotion relations in the People's Republic of China. AB - We conducted a questionnaire study to test the generality of attribution-emotion relations to individuals in the People's Republic of China. Replications of prior findings of studies conducted with American subjects were reported: (a) High effort and success enhanced interpersonal evaluations when ability, effort, and outcome information were provided; (b) affective communications of pity, anger, and guilt were respectively used to infer low ability, lack of effort, and teacher as causes of failure; (c) effort and ability levels were inferred from the presence or absence of anger reactions; and (d) controllable causes of a broken social contract were expected to result in anger from others. Chinese and American respondents also indicated what situations would arouse the affects of anger, guilt, pity, pride, and shame. We found no evidence for the characterization of Chinese as (a) emphasizing effort over ability as a cause of achievement outcomes or (b) de-emphasizing the importance of personal achievement and stressing group goals and accomplishments. PMID- 2926615 TI - Perceiving choice and constraint: the effects of contextual and behavioral cues on attitude attribution. AB - We examined how features of the situation and the target's behavior in the attitude-attribution paradigm may lead observers to infer that the behavior was performed purposefully and how these perceptions may contribute to correspondence bias. Experiment 1 demonstrated that cues suggesting that essay assignment resulted from the target's purposeful action lead to correspondent inferences. When these cues were absent, observers' inferences were not correspondent. Experiment 2 demonstrated that observers are sensitive to cues emitted by the target (facial expressions of delight and disappointment) and that those cues' meaning depends on the context in which they take place. When the essay was freely chosen, the expression had little effect; observers judged that the essay accurately reflected the target's attitudes. When the essay assignment was constrained, observers used the expressions to discount the essay when judging the target's attitudes. We discuss the implications of these findings for the study of correspondent inferences and correspondence bias. PMID- 2926614 TI - Causal models of adolescent substance use: an examination of gender differences using distribution-free estimators. AB - On the basis of previous literature (Hays, Widaman, DiMatteo, & Stacey, 1987; Huba, Wingard, & Bentler, 1981), four alternative causal models of substance use were specified, estimated, and evaluated for adequacy of statistical fit for samples of White male (N = 9,164) and female (N = 8,421) adolescents. Results supported the adequacy of a four-variable simplex model, in which alcohol use predicted marijuana use, and marijuana use predicted enhancer and dampener hard drug use. The four-variable simplex model was robust across the male and female adolescent samples. In addition, we found comparisons of maximum likelihood and asymptotically distribution-free estimators to be relatively robust across the causal models specified with respect to the magnitude of the parameter estimates, and with respect to the significance levels of the critical ratios, although chi square model fit statistics for the maximum likelihood estimates were highly inflated. PMID- 2926616 TI - Intuitive interactionism in person perception: effects of situation--behavior relations on dispositional judgments. AB - To examine the effects of the relationships between behavior and the situation in which it occurs, we manipulated such relations and exposed subjects to them. Impressions were similar when based on the behaviors presented with situations unspecified (e.g., child hits) or when the situations in which they naturally occurred were specified (e.g., child hits when provoked). However, when situations were specified, subjects' impressions more accurately predicted individual differences in the children's actual levels of overall aggressive behavior. When the veridical situation-behavior relations were increasingly altered, the targets were perceived as being less plausible and increasingly maladjusted and odd, and correlations decreased between the perceived level of the children's aggressiveness and their actual aggressive behavior. Thus, both personality impressions and predictive accuracy were influenced by the relations between the target's behaviors and their situational contexts. PMID- 2926617 TI - Role of competition-induced anxiety in limiting the beneficial impact of positive behavior by an out-group member. AB - Several variables influence whether contact with a favorable out-group member has a beneficial impact on intergroup relations. In two experiments we examined the effect of competition-induced anxiety on reaction to the behavior of a favorable out-group member. In Experiment 1 a competitive context produced (a) anxiety, relative to a cooperative context, and (b) assimilation of a favorable out-group member to the unfavorable majority. Experiment 2 replicated this finding and showed that when anxiety was reduced, those who expected to compete with the out group formed a more favorable and veridical impression of the positive out-group member. Taken together, results support the hypothesis that the expectation of an unpleasant competitive encounter with an out-group generates anxiety that, in turn, lessens the impact of positive behavior by an out-group member. Implications of this research for intergroup relations are discussed. PMID- 2926618 TI - Appraisal of life change, depression, and illness in hardy and nonhardy women. AB - A survey study of adult women was conducted to examine whether psychological hardiness buffers people against stressful life change through the appraisal and interpretation of life experiences. Hardy and nonhardy participants reported life events for the previous year, physical illness for the previous 6 months, and current levels of depression and rated each reported event in terms of its desirability. Results indicate that, although hardiness is not associated with the likelihood of reporting any specific life event, nonhardy subjects appraise a significantly higher proportion of their life experiences as undesirable than do hardy subjects and report that each negative event requires greater adjustment. Discussion focuses on nonhardiness as a correlate of the trait of negative affectivity rather than hardiness as a reflection of special resiliency to stress. PMID- 2926619 TI - Sex typing and gender ideology: two facets of the individual's gender psychology that go together. AB - Three studies tested the hypothesis that gendered personality dispositions are related to gender attitudes and gender discriminatory behaviors. In Study 1, sex typed individuals were more likely than androgynous, undifferentiated, and cross sex-typed individuals to accept gender rules designating culturally appropriate behavior for men and women. In Study 2, sex-typed individuals were particularly likely to pay attention spontaneously to the sex of job applicants and then to devalue the interview performances of women. In Study 3, only sex-typed men tended to endorse sexist language. As expected, sex typing and gender ideology go together. This relation between two facets of the individual's gender psychology indicates that some sex role inventories may tap more than expressivity and instrumentality. PMID- 2926620 TI - Conversation memory: the effects of speaker status on memory for the assertiveness of conversation remarks. AB - We conducted three experiments to examine the effects of information about a speaker's status on memory for the assertiveness of his or her remarks. Subjects either read (Experiments 1 and 2) or listened to a conversation (Experiment 3) and were later tested for their memory of the target speaker's remarks with either a recognition (Experiment 1) or a recall procedure (Experiments 2 and 3). In all experiments the target speaker's ostensible status was manipulated. In Experiment 1, subjects who believed the speaker was high in status were less able later to distinguish between remarks from the conversation and assertive paraphrases of those remarks. This result was replicated in Experiment 2, but only when the status information was provided before subjects read the conversation and not when the information was provided after the conversation had been read. Experiment 2's results eliminate a reconstructive memory interpretation and suggest that information about a speaker's status affects the encoding of remarks. Experiment 3 examined this effect in a more ecologically representative context. PMID- 2926621 TI - Effects of instructional set on attributions of nonvolition during hypnotic and nonhypnotic analgesia. AB - Fifty highly hypnotizable subjects were assigned to four treatment groups or a no treatment control group and then underwent two pain stimulation trials. Half the treated subjects were administered hypnotic analgesia, half waking analgesia. Within hypnotic and nonhypnotic treatments, half the subjects were given actively worded analgesia instructions, half passively worded instructions. Subjects in the four treated groups reported equivalent pain reduction and equivalent use of coping imagery, although hypnotic subjects rated themselves as more deeply hypnotized than did nonhypnotic subjects. Both hypnotic and nonhypnotic subjects given passive instructions rated their pain reduction as occurring involuntarily, whereas those given active instructions reported that their pain was reduced through their active use of coping strategies. These findings support sociocognitive formulations of hypnotic responding that view ratings of involuntariness as reflecting contextually guided interpretations of behavior. PMID- 2926622 TI - Directed forgetting and posthypnotic amnesia: information processing and social contexts. AB - In three experiments we compared posthypnotic amnesia (PHA) with directed forgetting (DF), evaluating subjects' hypnotic susceptibility, hypnotized or not. Experiment 1 suggested that the memory processes in PHA and DF were not the same. Low and high susceptibility subjects responded differently in the two contexts. Experiment 2 demonstrated a context effect for highly susceptible subjects: They showed the usual DF response outside hypnosis but not during hypnosis. Experiment 3 showed that high and low susceptibility subjects responded similarly to DF instructions outside hypnosis, eliminating the susceptibility as an important variable in the DF response. We concluded: (a) The interaction of context and susceptibility was the important determinant of unusual DF responses for high susceptibles, and (b) information processing concepts are too limited to explain PHA and perhaps DF. Theories that include interactions appear necessary for an accurate understanding of hypnotic phenomena and perhaps some phenomena usually focused on by cognitive psychology. PMID- 2926623 TI - That's easy for you to say: action identification and speech fluency. AB - Action identification theory holds that an action can be identified by the performer in different ways, and that these various act identities differ in their appropriateness for maintaining the action effectively. Optimal action identification exists when a personally easy action is identified in relatively high-level terms (i.e., the action's effects and implications) or a personally difficult action is identified in relatively low-level terms (i.e., the action's mechanical details). To test the optimality hypothesis with respect to speech fluency, subjects were asked to deliver a speech to either an easy-to-persuade audience or a difficult-to-persuade audience and induced to think about the action in either high-level or low-level terms. As predicted, subjects made fewer speech errors and felt more satisfied with their performance when the task was personally easy and identified at high level and when the task was personally difficult and identified at low level. Optimal action identification made things easier for them to say. PMID- 2926624 TI - Cardiovascular reactivity and interpersonal influence: active coping in a social context. AB - Previous studies have demonstrated that effortful attempts to secure positive outcomes or avoid negative outcomes produce significant increases in systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR). Although these effects of active coping on cardiovascular reactivity are central in current psychosomatic theories, virtually all of the research to date has used impersonal, asocial tasks. Our two studies examined the cardiovascular effects of effortful attempts to influence other people. In Study 1, male subjects attempting to influence the opinions of their discussion partner to improve their own chances of winning money displayed significantly greater SBP, DBP, and HR reactivity. In Study 2, we obtained similar effects on SBP and DBP reactivity in men and women, while both preparing an influence attempt and making that attempt. Furthermore, reactivity levels were larger as the magnitude of incentive for successful persuasion increased. Implications of this interpersonal equivalent of active coping for the development of cardiovascular disease are discussed. PMID- 2926625 TI - Apology as aggression control: its role in mediating appraisal of and response to harm. AB - Two studies examined the effects of an apology on a victim's aggression and explored the psychological mechanisms underlying such effects. In Study 1, female undergraduates were psychologically harmed and then received an apology by another female student. In Study 2, male undergraduates were asked to role play a victim in a hypothetical harm situation. Results indicate that when the harm doers apologized, as opposed to when they did not, the victim-subjects refrained from severe aggression against them. Regression analyses suggested that such aggression-inhibitory effects of an apology were mediated by impression improvement, emotional mitigation, and reduction in desire for an apology within the victims. It was also found that when the harm was severe, such effects of an apology on aggression were attenuated. The more severe the harm is, the more extensive of an apology may be needed to alleviate the victim's anger and aggression. PMID- 2926626 TI - Effects of coping skills training on generalized self-efficacy and locus of control. AB - A number of studies have shown that mastery experiences strengthen self-efficacy expectancies that are specific to the mastery situation. In this study I assessed the effects of cognitive-behavioral coping skills training on generalized expectancies concerning self-efficacy and locus of control in test-anxious college students. Compared with a waiting-list control group, the trained subjects exhibited significant decreases on trait and state measures of test anxiety and a higher level of academic performance on classroom tests, as well as changes in specific self-efficacy expectancies relating to test-anxiety management and academic performance. Consistent with generalization predictions derived from self-efficacy theory, the coping skills group also exhibited decreases in general trait anxiety and increased scores on a trait measure of generalized self-efficacy. Locus of control was unaffected by the program, and changes in general self-efficacy were unrelated to changes in locus of control, suggesting the possibility that different parameters of experience are related to changes in the two types of generalized expectancies. PMID- 2926627 TI - Critique of the act frequency approach to personality. AB - Evaluates the the act frequency approach (AFA), noting that retrospective self reports rather than behavioral acts are studied; act context and meaning are not considered; the AFA self-report inventories are incompletely developed and are psychometrically unsound; the AFA claim of absolute measurement of dispositions is insupportable; many of the self-report act statements used are technically unacceptable or conceptually unwarranted; the research agenda of the AFA primarily involves only "internal analyses" of self-report "act" inventories and indices and proposes the further creation of "act" inventories to index thousands of conceptually unorderable dispositions. Were the problems involved in the current implementation of the AFA to be resolved, various large conceptual problems presently besetting the approach then would have to be confronted. PMID- 2926628 TI - The hardy personality: cognitive and physiological responses to evaluative threat. AB - Hardy persons are hypothesized to be resistant to stress-induced illness, because of their adaptive cognitive style and a subsequently reduced level of physiological arousal. We assessed the cognitive and physiological responses of high and low hardy male undergraduates to a challenging task under high and low evaluative threat. As predicted, hardy subjects endorsed more positive self statements than did low hardy subjects in the high threat condition. High hardy subjects also reported fewer negative self-statements overall, but this was attributable to the overlap of measures of hardiness and neuroticism. Hardy subjects displayed marginally lower arousal while waiting for the task to begin, but this finding did not approach significance when neuroticism was controlled. Hardy subjects also had higher levels of systolic blood pressure, perhaps because of their active coping efforts. Results support the hypothesized hardy cognitive style but raise questions about the type and timing of organismic strain linking hardiness and health. PMID- 2926629 TI - Assessing coping strategies: a theoretically based approach. AB - We developed a multidimensional coping inventory to assess the different ways in which people respond to stress. Five scales (of four items each) measure conceptually distinct aspects of problem-focused coping (active coping, planning, suppression of competing activities, restraint coping, seeking of instrumental social support); five scales measure aspects of what might be viewed as emotional focused coping (seeking of emotional social support, positive reinterpretation, acceptance, denial, turning to religion); and three scales measure coping responses that arguably are less useful (focus on and venting of emotions, behavioral disengagement, mental disengagement). Study 1 reports the development of scale items. Study 2 reports correlations between the various coping scales and several theoretically relevant personality measures in an effort to provide preliminary information about the inventory's convergent and discriminant validity. Study 3 uses the inventory to assess coping responses among a group of undergraduates who were attempting to cope with a specific stressful episode. This study also allowed an initial examination of associations between dispositional and situational coping tendencies. PMID- 2926630 TI - Personality correlates of physical fitness. AB - In this article, I examine the relation between personality and physical fitness. One group (N = 97) of male adults completed the Hogan Personality Inventory and five nationally recognized physical fitness batteries. A second group (N = 35) completed the Minnesota Multiphasic Personality Inventory and a set of medical and physical performance assessments. Results indicate that physical fitness must be defined in multidimensional terms and that fitness is related to self confidence and self-discipline. Measures of psychopathology were unrelated to measures of health and fitness. These data suggest that the personal qualities associated with fitness are also those that promote and extend health. PMID- 2926631 TI - On the degree of stability of measured hypnotizability over a 25-year period. AB - Conducted a longitudinal study of hypnotizability, as measured by the Stanford Hypnotic Susceptibility Scale, Form A, that yielded a relatively high degree of stability in hypnotic responsiveness over repeated testings spanning a 25-year period. The 50 Ss were retested in 1985, after tests when they were students, between 1958-1962 and again in 1970. The statistically significant stability coefficients were .64 (10-year retest), .82 (15-year retest), and .71 (25-year retest). The means did not change significantly, and the median change in the scores of individuals was only 1 point on the 12-item scale. A set of score measures and their intercorrelations are insufficient to resolve the issue of why stability occurs. The stability of hypnotizability over time compares favorably with that of other measures of individual differences. PMID- 2926632 TI - Intrapersonal and social comparison determinants of happiness: a range-frequency analysis. AB - Examined whether intrapersonal comparisons and social comparisons operate in similar ways to determine ratings of happiness. Events were varied to create positively and negatively skewed distributions. The events in each distribution were ascribed to either a single person or a group of people; Ss rated how happy they would feel if they experienced specific events within the distribution. Ratings for both intrapersonal and social comparisons were fit well by Parducci's (1984) range-frequency theory. Individual events received higher ratings when presented within the positively skewed context. Overall happiness, as measured by both the mean of the happiness ratings as well as direct ratings, was highest for the negatively skewed distributions. The effects of skewing were more pronounced for intrapersonal comparisons, but ratings were more closely defined by the range of experimental stimuli for social comparisons. PMID- 2926633 TI - Dimensions of appraisal and physiological response in emotion. AB - Appraisal theorists propose physiological activity in emotion to be systematically organized around appraisal of the adaptational significance of the environment in ways that promote two functions commonly ascribed to emotion: communication and preparation for coping. However, relations between appraisal and physiological activity remain largely untested. This article reviews existing evidence to generate specific hypotheses linking appraisal to physiological activity and presents an imagery-based experimental test of a subset of these hypotheses. No evidence was found for a relation between other-agency and the eyebrow frown, but brow activity and heart rate were affected by effort-related appraisals: Anticipated effort influenced heart rate, and perceived goal obstacles influenced the eyebrow frown. Implications of the findings and theoretical approach are discussed. PMID- 2926634 TI - Intergroup aggression: its predictors and distinctness from in-group bias. AB - Investigated predictors of intergroup aggression and its relations to in-group bias. In a questionnaire, 156 Israeli adults reported perceptions of their own religious group and of the ultraorthodox Jewish out-group and expressed aggression toward the ultraorthodox (opposing institutions that serve their needs, supporting acts harmful to them, and opposing interaction with them). Respondents showed in-group favoritism in trait evaluations, but this bias was unrelated to aggression. Perceived inter-group conflict of interests, the postulated motivator of aggression, predicted it strongly. The effects of conflict on aggression were partially mediated by 2 indexes of dehumanizing the out-group (perceived value dissimilarity and trait inhumanity) and by 1 index of probable empathy with it (perceived in-group-out-group boundary permeability). These variables related to aggression more strongly among persons who identified highly with their in-group. The variables also mediated the effects of religious group affiliation on aggression. The value dissimilarity finding supports derivations from belief congruence theory. PMID- 2926635 TI - The goal of forming accurate impressions during social interactions: attenuating the impact of negative expectancies. AB - Investigated the idea that impression formation goals may regulate the impact that perceiver expectancies have on social interactions. In simulated interviews, interviewers Ss were given a negative expectancy about one applicant S and no expectancy about another. Half the interviewers were encouraged to form accurate impressions; the others were not. As predicted, no-goal interviewers exhibited a postinteraction impression bias against the negative-expectancy applicants, whereas the accuracy-goal interviewers did not. Moreover, the ability of the accuracy goal to reduce this bias was apparently mediated by more extensive and less biased interviewer information-gathering, which in turn elicited an improvement in negative-expectancy applicants' performances. These findings stress the theoretical and practical importance of considering the motivational context within which expectancy-tinged social interactions occur. PMID- 2926636 TI - Task performance and perceptions of anxiety: averaging and summation in an evaluative setting. AB - Suggests that individuals' "stage fright," or perceptions of anxiety and performance, is a function of tendencies to both average and summate the impact of audience members. We found that under certain conditions adding an evaluative member to an audience decreased anxiety, whereas in other conditions the addition of evaluative members increased anxiety. These results are not expected from social impact theory or social facilitation research and suggest that individuals do not react to groups of individuals in a manner analogous to the way in which trait information is typically averaged in forming impressions of individuals (Anderson, 1981). An averaging-summation model that does account for these findings is presented. This research has implications for research on crowding, stress, social influence, and affective responses. PMID- 2926637 TI - Impact of conceptions of ability on self-regulatory mechanisms and complex decision making. AB - Tested the hypothesis that induced conceptions of ability as a stable entity or as an acquirable skill would affect self-regulatory mechanisms governing performance in a simulated organization. Ss served as managerial decision makers in which they had to match employees to subfunctions and to discover and apply managerial rules to achieve a difficult level of organizational performance. Those who performed the challenging managerial task under an entity conception of ability suffered a loss in perceived self-efficacy, lowered their organizational goals, and became less efficient in their analytic strategies. Ss who managed the organization under an acquirable skill conception of ability sustained their perceived self-efficacy, set challenging organizational goals, and used analytic strategies effectively. These divergences in self-regulatory factors were accompanied by substantial differences in organizational performance. Path analysis revealed that perceived self-efficacy had both a direct effect on organizational performance and an indirect effect through its influence on analytic strategies. Personal goals also affected organizational performance through the mediation of analytic strategies. The relation of prior organizational performance to subsequent performance was mediated entirely by the combined influence of the self-regulatory factors. PMID- 2926638 TI - Processing of ambiguous and unambiguous feedback by depressed and nondepressed college students: schematic biases and their implications for depressive realism. AB - Explored schematic processing as a mechanism for predicting (a) when depressed Ss would be negative relative to nondepressed Ss and (b) when depressed and nondepressed Ss would show biased or unbiased (i.e., "realistic") processing. Depressed and nondepressed Ss performed multiple trials of a task under conditions in which the two groups held either equivalent or different schemas regarding this task. Ss received either an unambiguous or objectively normed ambiguous feedback cue on each trial. In full support of schematic processing, depressed Ss showed negative encoding relative to nondepressed Ss only when their schemas were more negative, and both depressed and nondepressed Ss showed positively biased, negatively biased, and unbiased encoding depending on the relative feedback cue-to-schema match. Depressed and nondepressed Ss' response latencies to unambiguous feedback also supported the occurrence of schematic processing. We discuss the methodological, treatment, and "realism" implications of these findings and suggest a more precise formulation of Beck's schema theory of depression. PMID- 2926639 TI - Rater bias in the EASI temperament scales: a twin study. AB - Under trait theory, ratings may be modeled as a function of the temperament of the child and the bias of the rater. Two linear structural equation models are described, one for mutual self- and partner ratings, and one for multiple ratings of related individuals. Application of the first model to EASI temperament data collected from spouses rating each other shows moderate agreement between raters and little rating bias. Spouse pairs agree moderately when rating their twin children, but there is significantly rater bias, with greater bias for monozygotic than for dizygotic twins. MLE's of heritability are approximately .5 for all temperament scales with no common environmental variance. Results are discussed with reference to trait validity, the person-situation debate, halo effects, and stereotyping. Questionnaire development using ratings on family members permits increased rater agreement and reduced rater bias. PMID- 2926640 TI - Perceptions of control, competence, and contingency as influences on the stress behavior symptom relation in school-age children. AB - Analyzed data from 154 school-age children and their mothers to examine the relations between stress, perceived competence and contingency, and behavior symptoms. Analyses focused on the relative merits of unidimensional vs multidimensional measures of control in predicting symptoms. The stress of undesirable life events and behavior symptoms were related in the expected direction. Multiple regression models with R2 ranging from .11 to .14 (all ps less than .0002) included significant main effects for stress, competence, and control. Analyses supported the relative superiority of the multidimensional measure of control. Models containing main effects and interaction terms were of equivalent magnitudes in accounting for variance in symptom scores. Findings support the idea of perceived control as a moderator of the stress-illness relation and are consistent with earlier suggestions that simple main effects models may be the most useful in examining these relations. PMID- 2926641 TI - Goal utility, task satisfaction, and the self-appraisal hypothesis of type A behavior. AB - Strube's (1987) self-appraisal model of Type A behavior suggests that externally mediated performance goals that are useful for assessing task-related competencies will possess greater utility and be more satisfying to Type A persons than to Type B persons. In contrast, because Type Bs may have an aversion to competency verifications, they should be more satisfied than Type As when goals are uninformative about task-related competencies. The 102 undergraduate Ss performed either a word puzzle or proofreading task under 1 of 4 goal conditions that varied in terms of the goal's instrumentality for assessing competencies and for obtaining a financial incentive. Results are generally consistent with this prediction, thereby providing verification for one of the more basic propositions derived from the self-appraisal model. PMID- 2926642 TI - Explanatory style across the life span: evidence for stability over 52 years. AB - Analyzed explanatory style across the life span. 30 Ss whose average age was 72 responded to questions about their current life and provided diaries or letters written in their youth, an average of 52 years earlier. A blind content analysis of explanatory style derived from these 2 sources revealed that explanatory style for negative events was stable throughout adult life (r = .54, p less than .002). In contrast, there appeared to be no stability of explanatory style for positive events between the same 2 time periods. These results suggest that explanatory style for negative events may persist across the life span and may constitute an enduring risk factor for depression, low achievement, and physical illness. PMID- 2926643 TI - Personal striving differentiation and affective reactivity. AB - Examined the relation between affective reactivity (intensity and variability of mood) and cognitive differentiation through the personal striving (Emmons, 1986) framework in order to test the hypothesis that affective reactivity underlies differentiation. 88 Ss in 2 samples listed 15 of their personal strivings and rated them with respect to 3 measures of striving differentiation (interdependence, dissimilarity, and plans for accomplishing each). Experience sampling and daily mood ratings were used to assess affect intensity and affect variability over a 3-week period. Emotionally reactive Ss possessed a more differentiated striving system. However, they generated fewer plans for accomplishing each striving than did less reactive Ss. Results are interpreted in terms of Larsen and Diener's (1987) arousal regulation theory of affect intensity and Linville's (1982, 1985) self-complexity/affect-extremity model. PMID- 2926644 TI - Nursing frontiers. Critical care in the air. PMID- 2926645 TI - Bad scare on good friday. PMID- 2926646 TI - Confessions of a happy camper. PMID- 2926647 TI - Deception at a new age clinic. PMID- 2926648 TI - The psychiatric nursing shortage and the HIV epidemic: a call to action. PMID- 2926649 TI - Improving nursing care services for children and adolescents with severe emotional disorders. AB - The purpose of this article is to address the educational and training needs of students in programs designed to prepare advanced nurse clinicians in child and adolescent psychiatric nursing in order to improve the care of severely emotionally and behaviorally disturbed (SED) children. To accomplish this task, several related issues have been addressed. These include: information on the types and rates of disorders in children, variables associated with psychopathology in children and adolescents, psychiatric care needs and the settings in which interventions occur, information about child and adolescent psychiatric nurses, and the current status of the educational scene for child and adolescent psychiatric nurses. Finally, recommendations for strategies to improve the care of SED children and their families are presented. PMID- 2926650 TI - Children and adolescents with AIDS: mobilizing for care. Clinical concerns and recommendations. PMID- 2926651 TI - Children and adolescents with AIDS: mobilizing for care. An international report. PMID- 2926652 TI - Development of the PAAI as a measure of attitudes of parents with preschool children toward substance use and abuse. AB - Because parents have a major impact on their preschool children's development, the study of parental attitudes is crucial to understanding substance abuse behavior. This study examined the reliability of an instrument to measure attitudes of parents with preschool children regarding substance use and abuse. The sample consisted of a lower to middle socioeconomic, racially diverse population of 101 parents of preschool children. The Parent Attitude Assessment Instrument (PAAI) measured parents' attitudes toward substance use and abuse, parental role modeling, and substance abuse prevention with preschool children. PMID- 2926653 TI - The manipulator reputation in juvenile detention: collective labeling in a total institution. AB - Adolescent manipulative behaviors are the focus of a combined field study and literature review. A taxonomy of manipulation generated within the setting of a large metropolitan juvenile detention facility is compared with literature sources and examined from the theoretical construct of a total institutional behavioral environment. Issues are raised which require consideration in planning nursing care for this and similar client populations. PMID- 2926654 TI - Adolescent suicide: assessment and intervention. AB - Understanding how to prevent suicide, the third leading cause of adolescent death, is the focus of this article. To prevent suicide, the nurse assesses risk factors, covert messages, overt suicide clues, and intervenes with the adolescent and family. Suicide risk and hopelessness decrease as suicidal youths learn to clarify problems, rally significant others, expand resources and use safe coping strategies. Interventions include a no-suicide contract, family therapy and school suicide prevention programs. Nurses can identify the youth at risk for suicide and, in many cases, provide the therapy that helps prevent suicide. Vignettes illustrate strategies that effectively reduce suicide risk. PMID- 2926655 TI - Our new Huck Finn: foster care and the nurse. PMID- 2926656 TI - Insuring a normal school environment for a teenager with AIDS. PMID- 2926657 TI - Psychiatric and mental health nurses' beliefs about therapeutic paradox. AB - Therapeutic paradox is a subject that elicits divergent opinions among psychiatric and mental health nurses. In a study of a random, systematic sample of psychiatric nurses (N = 165), more than one-half of the respondents used paradox and a larger majority of respondents considered paradox to be an appropriate psychotherapeutic intervention, although there were expressions of professional and ethical reservation. In addition to holding more negative beliefs about manipulation, threats to the therapeutic relationship, and deception, the non-users of paradox were significantly less willing to refer friends for paradoxical treatment. PMID- 2926658 TI - Spleen cellularity shifts from the inhalation of 0.25-0.35 PPM nitrogen dioxide. AB - The effects of ambient level (0.25-0.35 ppm)NO2 on percent spleen cell counts, relative percentages of spleen lymphocyte subpopulations, spleen lymphoid nodule size, and differential peripheral blood cell counts were investigated in 170 young adult male mice following various NO2 exposure periods. The total spleen cell counts, surface IgM-positive lymphocytes and spleen mean lymphoid nodule area were all significantly decreased in the groups exposed to NO2 following extended time periods. The relative percentages of peripheral blood lymphocytes were also significantly decreased in the groups exposed to NO2 for 8 weeks. The mechanism for these observed spleen changes following ambient level NO2 exposure remains unclear, but the results warrant further investigation and concern, especially since such changes may reflect altered immune responsiveness. PMID- 2926659 TI - Evidence for the covalent interaction of carbon tetrachloride with mouse liver chromatin DNA in vitro. AB - Whole chromatin was isolated from livers of 8-12 week-old male B6C3Fl hybrid mice and incubated with 14C-labelled carbon tetrachloride (14CCL4) in the presence of hepatic microsomes from the same animals and an NADPH-regenerating system. The experiments were carried out at various concentrations of 14CCl4 and incubation times. Under the conditions used, 14CCl4 metabolite(s) bind quantifiably to chromatin DNA (ch.DNA) in direct response to increases in 14CCl4 concentration and incubation time. Maximal binding (0.34 nmoles/mg DNA) occurs at 2 hrs when 10 umoles 14CCl4 was used for the incubation. Binding of 14CCl4 metabolite(s) to ch.DNA was/were significantly inhibited (84%) in the presence of the strong nucleophile, L-cysteine (5 mM). These results provide evidence for the covalent interaction of CCl4 metabolite(s) with DNA when organized as chromatin under aerobic incubation condition, which suggest the importance of the higher-order organization of DNA in chromatin and its reactivity with CCl4 metabolite(s). PMID- 2926661 TI - Nitrogen dioxide (NO2) inhalation, formation of microthrombi in lungs and cancer metastasis. AB - It is recognized that cancer cells may be introduced into circulation during surgical removal of a malignant neoplasm. The fate of these cells depends upon many factors. In this paper we present findings from an animal model which indicate that inhalation of nitrogen dioxide facilitates blood-borne cancer cell metastasis to lungs by injuring lung capillary endothelium and formation of microthrombi. Lung capillaries were evaluated by light and electron microscopy. The main lesions observed were microthrombi and injury to capillary endothelial cells, following 6 weeks of 0.35 +/- 0.05 ppm NO2 exposure. The blood-borne cancer cell metastasis was studied utilizing B16 melanoma cells in C57Bl/6J mice. A correlation was observed between increased incidence of microthrombi, endothelial cell injury and lung metastasis in exposed animals. Other adverse NO2 effects such as impairment of immune system may also participate. Inhalation of nitrogen dioxide and other air pollutants may play a significant role in enhancement of metastasis and blood vessel associated disorders. PMID- 2926660 TI - Ultrastructure of kidney of ducks exposed to methylmercury, lead and cadmium in combination. AB - Ultrastructural alterations in the kidneys of Pekin ducks exposed to various combinations of methylmercury chloride (MeHgCl), lead acetate (PbAC) and cadmium chloride (CdCl2 for 12 weeks were studied. Eight groups (Gr), each consisting of 6 female ducks, were fed diets containing no heavy metals (control), 8 mg of methylmercury chloride (MeHgCl)/kg of feed (GrII), 80 mg of lead acetate (PbAC)/kg of feed (GrIII), 80 mg of cadmium chloride (CdCl2)/kg of feed (GrIV), 8 mg of MeHgCl + 80 mg of PbAC/kg of feed (GrV), 8 mg of MeHgCl + 80 mg of CdCl2/kg of feed (GrVI), 80 mg of PbAC + 80 mg of CdCl2/kg of feed (GrVII), and 8 mg of MeHgCl + 80 mg of PbAC + 80 mg of CdCl2/kg of feed (GrVIII). Renal corpuscles of the ducks treated with methylmercury (MdHg), lead (Pb), the cadmium (Cd), either alone or in two way combinations exhibited minor ultrastructural changes. The thickness of the glomerular basement membrane was significantly different from control only in Grs II, IV, V and VI. Crystallization of granules in the juxtaglomerular cells was also observed in Cd and Pb treated birds. Administration of the three metals in combination caused marked changes in podocytes with fusion of secondary processes and no pedicle differentiation. The proximal tubule cells approximately (PT) accumulated lipid droplets, lysosomal bodies and membrane bound vacuoles in methylmercury treated birds. Lead exposed birds had a large number of secondary lysosomes and swollen mitochondria in PT cells. Cadmium administration caused degenerative changes in PT cells which included accumulation of lysosomal bodies containing degenerating organelles, lipid droplets and vacuoles containing myelin figures. Marked degenerative changes in PT cells and interstitial fibrosis was prominent when cadmium was concomitantly administered with the other metals. Concurrent administration of all three metals caused enhancement of degenerative changes in proximal tubule cells and collecting duct cells. These observations suggest that the combined administration of metals causes renal damage that appears to be additive. PMID- 2926662 TI - Testicular dysfunction induced by cadmium and its improvement caused by selenium in the mouse. AB - Histological observation revealed widespread and severe necrosis at 3 days after the final injection of Cd (0.012 mmol/Kg. daily for 2 consecutive days). Two months later, the changes were further aggravated. In addition, severe atrophy was found, and there was an increase in materials which could be stained by the Kossa method. These changes were prevented by the simultaneous injection of Se (0.024 mmol/Kg, daily for 2 consecutive days). Two months later, the Cd group showed no longer its reproduction. As a result of the Cd injection, at 3 days lipoperoxide concentration, expressed as substances reacting with thiobarbituric acid, was increased significantly, and accompanied by a decrease of glutathione. The levels of lipoperoxide and glutathione values were restored to the control level by the Se injection. At 3 days, testicular Zn and Mg decreased significantly, but Ca and Fe increased markedly in the Cd group. Ca increased mainly in the slow-speed centrifugation fraction, while Mg decreased evenly. In the Cd + Se group, there was no detectable change of metal concentration. However, Se stimulated the Cd uptake into the testis and vice versa. The testicular Cd and Se contents were maintained at a constant level for 2 months. The proportions of Cd existing in the cytosol fraction were 80% and 45% in the Cd group and the Cd + Se group, respectively. Furthermore, the recovery rates for cytosolic Cd in the F2 fractions corresponding to metallothionein were 60% and 75% in the Cd and Cd + Se groups, respectively. Our results suggest that Se has multiple functions against testicular Cd toxicity and that the toxicity once blocked by Se does not occur for a relatively long time. PMID- 2926663 TI - Mechanical properties of rabbit lung with edema caused by exposure to ozone. AB - Rabbits were intermittently exposed to ozone (O3) and the mechanical properties of their lungs were studied in order to know details of ventilatory functions in lung injuries caused by this gas. The lungs of rabbits exposed to 2 ppm O3 for 6 hours daily for 3 days showed the earlier stage of edema, and tended to trap air as distending pressure was lowered at the measurement of volume-pressure relationship. In this group of animals, dynamic compliance decreased, pulmonary flow resistance increased, and flow-volume curve obtained by forced deflation showed a definitely altered slope with reduced flows at the latter part of descending limb. On the other hand, the significant change observed in rabbits exposed to 1 ppm O3 for 6 hours daily for 7 days was only the increase in pulmonary flow resistance: the extent was similar to that observed in the former group of rabbits. Light-microscopical study for the airways of O3-exposed rabbits revealed varying degrees of epithelial damages and submucosal edema in the large airways and in terminal and respiratory bronchioles, and thickening of alveolar walls in the proximal alveolar ducts, being much more evident in the former group. PMID- 2926664 TI - Prenatal diagnosis of genetic disorders. PMID- 2926665 TI - Genetic counseling: the emerging reality. PMID- 2926666 TI - Multifactorial inheritance: implications for perinatal and neonatal nurses. PMID- 2926667 TI - Congenital defects: parental issues and nursing supports. PMID- 2926669 TI - Rehabilitation R & D Progress Reports 1988. PMID- 2926668 TI - A primer to the inborn errors of metabolism for perinatal and neonatal nurses. PMID- 2926670 TI - Infectious diarrhea. Your CE topic (No. 37). Update on the management of infectious diarrhea. PMID- 2926671 TI - Informal contracting--a solution to problem patients. PMID- 2926672 TI - Jamie: the story of a terminal patient. PMID- 2926673 TI - Why I want to be an LPN. PMID- 2926674 TI - And why I choose to remain an LPN. PMID- 2926675 TI - Drug and alcohol abuse medical record confidentiality. PMID- 2926677 TI - A cure for repetition, redundancy, and hyperbole. PMID- 2926678 TI - The joy of building a free-standing ambulatory surgery center. PMID- 2926676 TI - Treatment of SLE. Your CE topic (No. 38). The treatment of systemic lupus erythematosus. PMID- 2926679 TI - Practical points in the care of patients following transsphenoidal surgery. PMID- 2926680 TI - The pediatric patient. PMID- 2926682 TI - Examples of samples. PMID- 2926681 TI - Today's manager: surviving or thriving? PMID- 2926683 TI - The legislative process: become involved. PMID- 2926684 TI - Care of the patient with malignant hyperthermia. PMID- 2926686 TI - PACU visiting policies. PMID- 2926685 TI - Looking back to the future: a case for historical research. PMID- 2926687 TI - Self-serving biases in the perception of freedom: the impact of previously experienced failure. AB - The purpose of five experiments was to investigate the use by Israeli students of a perceived lack of freedom as a self-protective device against the negative implications of poor performance in an achievement task. I hypothesized that a reduction in perceived freedom might be used to protect self-esteem following failure. A reduction in perceived freedom would weaken a person's sense of responsibility for failure and thereby protect self-esteem. Experiments 1 and 2 showed that subjects exposed to failure retrospectively reported having had less freedom during the experimental sessions than those who experienced success or no feedback at all. Experiments 3, 4, and 5 demonstrated that failure reduces the perception of freedom when other external rationalizations for failure (high consensus, high distinctiveness, low consistency) are unavailable. The results are interpreted in the light of self-protective strategies. PMID- 2926688 TI - The emotional adjustment of children with Tourette's syndrome. AB - We investigated the predictive value of family reaction and illness severity with respect to the emotional adjustment of Tourette's syndrome patients. The subjects included 30 children with Tourette's syndrome and 30 control subjects matched on age, sex, race, and socioeconomic status. The predictor variables included the child's perception of parental behavior, family adaptability as perceived by the mother, mother's self-concept, and illness severity. The results indicated that the children's perceptions of their parents' behavior explained the most variance in children's self-concepts and anxiety for both groups. These findings highlight the importance of the parent-child interaction in predicting the child's emotional adjustment to Tourette's syndrome. PMID- 2926689 TI - The effect of applicant age, job level, and accountability on perceptions of female job applicants. AB - We used simulated videotaped employment interviews to assess the effect of accountability on impressions of female job applicants. One hundred and twenty American undergraduates majoring in business and personnel related areas were informed that they would be participating in the pilot testing of a new employee placement technique. The age of the job applicant (25, 40, or 55 years), the position for which they were being considered (assistant director or director), and the degree to which subjects were made to feel accountable for their impressions of the applicant (low or high accountability) were manipulated, resulting in a 3 x 2 x 2 between-subjects design. The predicted interaction between accountability and applicant age applicant age was found on age-related adjective checklist items. Increasing the subjects' accountability produced more stereotypical impressions of all applicants, along with a tendency to attribute the applicant's behavior to dispositional factors. PMID- 2926690 TI - Physiology and pharmacology of acetylcholinergic responses of interneurons in the antennal lobes of the moth Manduca sexta. AB - 1. Neurons in the antennal lobe (AL) of the moth Manduca sexta respond to the application, via pressure injection into the neuropil, of acetylcholine (ACh). When synaptic transmission is not blocked, both excitatory (Fig. 2) and inhibitory (Fig. 3) responses are seen. 2. Responses to ACh appear to be receptor mediated, as they are associated with an increase in input conductance (Figs. 2B and 3B) and are dose-dependent (Fig. 2 C). 3. All neurons responsive to ACh are also excited by nicotine. Responses to nicotine are stronger and more prolonged than responses to ACh (Fig. 4C). No responses are observed to the muscarinic agonist, oxotremorine (Fig. 4 B). 4. Curare blocks responses of AL neurons to applied ACh, while atropine and dexetimide are only weakly effective at reducing ACh responses (Figs. 5 and 6). 5. Curare is also more effective than atropine or dexetimide at reducing synaptically-mediated responses of AL neurons (Fig. 7). 6. In one AL neuron, bicuculline methiodide (BMI) blocked the IPSP produced by electrical stimulation of the antennal nerve, but it did not reduce the inhibitory response to application of ACh (Fig. 8). PMID- 2926691 TI - A comparison of signal detection between an echolocating dolphin and an optimal receiver. AB - An electronic simulated target apparatus was used in a two-experiment study to compare the target detection performance of an echolocating bottlenose dolphin with an optimal receiver. Random Gaussian noise with a relatively flat spectrum from 20 to 160 kHz was used as a masking source. Experiment I was conducted to establish a technique for estimating the echo energy-to-noise ratio, Ee/N, at the dolphin's threshold of detection. Dolphins typically vary the amplitude of their emitted signal over a large range making it difficult to estimate Ee/N. In the first part of experiment I, the simulated echo was a double click, the pulses separated by 200 microseconds, with each pulse being a replica of the dolphin's transmitted signal. A staircase psychophysical procedure was used to obtain the detection threshold, and the echo energy-to-noise ratio based on the highest amplitude click emitted per trial, (Ee/N)max, was determined at each reversal point. The second echo type consisted of one of the animal's echolocation clicks, previously measured, digitized and stored in an erasable programmable read-only memory (EPROM). The electronic target simulator was modified so that every time the dolphin emitted an echolocation signal, the EPROM was triggered to produce two pulses separated by 200 microseconds. On any trial, the EPROM signal was played back at a fixed amplitude, regardless of the amplitude of the dolphin's emitted signal. The Ee/N obtained with the EPROM signal at threshold was found to be 2.9 dB lower than (Ee/N)max obtained with the normal phantom target. Therefore an estimate of Ee/N can be obtained by subtracting 2.9 dB from (Ee/N)max.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2926692 TI - Physiology of lateral line mechanoreceptive regions in the elasmobranch brain. AB - The physiology of mechanoreceptive lateral line areas was investigated in the thornback guitarfish, Platyrhinoidis triseriata, from medulla to telecephalon, using averaged evoked potentials (AEPs) and unit responses as windows to brain functions. Responses were analysed with respect to frequency sensitivity, intensity functions, influence of stimulus repetition rate, response latency, receptive field (RF) organization and multimodal interaction. 1. Following a quasi-natural vibrating sphere stimulus, neural responses were recorded in the medullary medial octavolateralis nucleus (MON), the dorsal (DMN) and anterior (AN) nucleus of the mesencephalic nuclear complex, the diencephalic lateral tuberal nucleus (LTN), and a telencephalic area which may correspond to the medial pallium (Figs. 2, 3, 13, 14, 15, 16). 2. Within the test range of 6.5-200 Hz all lateral line areas investigated responded to minute water vibrations. Best frequencies (in terms of displacement) were between 75 and 200 Hz with threshold values for AEPs as low as 0.005 microns peak-to-peak (p-p) water displacement calculated at the skin surface (Fig. 6). 3. AEP-responses to a vibrating sphere stimulus recorded in the MON are tonic or phasic-tonic, i.e., responses are strongest at stimulus onset but last for the whole stimulus duration in form of a frequency following response (Fig. 3). DMN and AN responses are phasic or phasic tonic. Units recorded in the MON are phase coupled to the stimulus, those recorded in the DMN, AN or LTN are usually not (Figs. 5, 8, 9). Diencephalic LTN and telencephalic lateral line responses (AEPs) often are purely phasic. However, in the diencephalic LTN tonic and/or off-responses can be recorded (Fig. 11). 4. For the frequencies 25, 50, and 100 Hz, the dynamic intensity range of lateral line areas varies from 12.8 to at least 91.6 dB (AEP) respectively 8.9 and 92 dB (few unit and single unit recordings) (Fig. 7). 5. Mesencephalic, diencephalic, and telecephalic RFs, based on the evaluation of AEPs or multiunit activity (MUA), are usually contralateral (AN and LTN) or ipsi- and contralateral (telencephalon) and often complex (Figs. 10, 12, 16). 6. In many cases no obvious interactions between different modalities (vibrating sphere, electric field stimulus, and/or a light flash) were seen. However, some recording sites in the mesencephalic AN and the diencephalic LTN showed bimodal interactions in that an electric field stimulus decreased or increased the amplitude of a lateral line response and vice versa (Fig. 13 B). PMID- 2926693 TI - Genetic analyses of photoresponsiveness in the Djungarian hamster, Phodopus sungorus. AB - Endotherms living at temperate and arctic latitudes must adjust their physiology and behavior in order to survive seasonal change. The Djungarian hamster uses photoperiod to cue annual cycles of reproduction and thermoregulation, and its responses to short photoperiod include loss of body weight and change in pelage color. Some individuals do not exhibit these responses when exposed to short days. In this study individual variation in photoresponsiveness is quantified, and four lines of evidence for a genetic component to that variation are provided. First, two separate breeding stocks differed in both the percent of animals responding to a short-day lighting regimen (SD) and in the degree and timing of their response. Second, analysis of variance within and between families of full sibs for a photoresponsive index, PI (body weight loss +2 (molt index -1] following 12 weeks in SD demonstrated a significant family resemblance (intraclass correlation of 0.36 +/- 0.03). Third, heritability estimates from regression of offspring scores on parent scores for body weight loss, molt index and PI after 12 weeks in SD were 0.34 +/- 0.13, 0.36 +/- 0.10 and 0.37 +/- 0.12, respectively, indicating a strong additive genetic component for the three characters. Finally, a significant response occurred after one generation of artificial selection for and against photoresponsiveness. PMID- 2926694 TI - Interspecific variation in the visual pigments of deep-sea fishes. AB - Visual pigments in the rods of 38 species of deep-sea fish were examined by microspectrophotometry. 33 species were found to have a single rhodopsin with a wavelength of maximum absorbance (lambda max) in the range 470-495 nm. Such visual pigments have absorbance maxima close to the wavelengths of maximum spectral transmission of oceanic water. 5 species, however, did not conform to this pattern and visual pigments were found with lambda max values ranging from 451 nm to 539 nm. In 4 of these species two visual pigments were found located in two types of rod. Some 2-pigment species which have unusual red sensitivity, also have red-emitting photophores. These species have both rhodopsin and porphyropsin pigments in their retinae, which was confirmed by HPLC, and the two pigments are apparently located in separate rods in the same retinal area. In deep-sea fishes the occurrence of 'unusual' visual pigments seems to be correlated with aspects of the species' depth ranges. In addition to ecological influences we present evidence, in the form of lambda max spectral clustering, that indicates the degree of molecular constraint imposed on the evolution of visual pigments in the deep-sea. PMID- 2926695 TI - Lexical structure in Parsing long-distance dependencies. AB - We review a series of experiments investigating lexical influences in parsing sentences with long-distance dependencies. We report three primary results. First, gaps are posited and filled immediately following verbs that are typically used transitively, even when the filler is an implausible object of the verb. However, gaps are not posited after verbs that are typically used intransitively. Second, plausibility determines whether or not a filler is treated as the object of a verb when the verb is typically used with both a direct object and an infinitive complement. Finally, verb control information is used immediately in determining which noun phrase will be interpreted as the "understood" subject of an infinitive complement. PMID- 2926697 TI - Adjustment to illness and dropout of chemotherapy. AB - The study compares the adjustment to illness of a group of 53 cancer patients who dropped out of chemotherapy with a matched group of 53 cancer patients who completed their treatment. The patients were treated in five oncological institutes in Israel. We found differences both in the Psychosocial Adjustment to Illness Scale (PAIS) and Brief Symptom Inventory Scale (BSI). In both scales we found significant differences indicating that the degree of adjustment and the psychosocial distress of patients who dropped out of treatment was worse than that of patients who completed treatment. PMID- 2926696 TI - Evoked potentials and the study of sentence comprehension. AB - Evoked brain potentials were used to monitor moment-by-moment decisions during language comprehension. Subjects read sentences containing temporary syntactic ambiguities for which one of the possible interpretations was semantically implausible. The N400 component of the evoked potential, which is sensitive to implausibility, was used to discover when during a sentence subjects made a decision about the ambiguity. The results demonstrate that readers try to interpret a syntactic ambiguity early in a sentence rather than waiting for disambiguating information. This introduces a new way to use brain activity to study sentence comprehension processes. PMID- 2926698 TI - Type A behavior, coping mechanisms and emotions related to somatic risk factors of coronary heart disease in adolescents. AB - Type A behavior, coping mechanisms, emotions and somatic risk factors of coronary heart disease were studied in 208 randomly selected healthy adolescents. Type A behavior was evaluated by the Wolf-Hunter A-B Rating Scale and a questionnaire developed for the present study. Subjects' coping mechanisms and emotions were assessed by interviews. The somatic risk factors used were SBP, DBP, serum total cholesterol, LDL, HDL, triglycerides and body mass index. In boys, type A behavior consistently correlated negatively with somatic risk factors of CHD while in girls, 'traditional' type A components like impatience and a sense of hurry correlated positively with somatic risk. The key finding was that inability to recognize and express negative emotions and the denial of problems correlated with somatic risk. PMID- 2926699 TI - The effects of exercise training on mental well-being in the normal population: a controlled trial. AB - This study was designed to compare the effects of two aerobic training programmes of differing intensities on mood and mental well-being with those of a credible attention-placebo condition. One hundred and nine sedentary adult volunteers from the local population were assigned to four conditions: high intensity aerobic training, moderate intensity aerobic training, attention-placebo and waiting list. Training was carried out over a 10 week period. Subjects were assessed before and after training with psychological measures and the 12 min walk-run test, and follow-up evaluations were undertaken after 3 months. Ninety-four subjects began the programme and the adherence rate averaged 80%, with no significant differences in number of drop-outs between conditions. Appropriate changes in estimated maximum oxygen consumption were observed in the three active conditions with the 12 min walk-run test. Psychological benefits were seen with the moderate exercise condition but not in the high exercise or attention-placebo conditions. These effects were manifest immediately after training on measures of tension/anxiety and confusion, and at follow-up on measures of perceived coping ability. The mechanisms underlying this pattern of results are discussed and the relative importance for health of vigorous activity and physical fitness is considered. PMID- 2926700 TI - Understanding hypertensive behaviour--I. Preference not to disclose. AB - Preference not to disclose information was investigated as a likely explanation for low rates of report of concerns in hypertensives. The research was designed to explore alternative explanations that have been provided by others. Two studies investigated the effect of situational contexts which provided low or high social pressure to reveal personal life concerns. Results showed that degree of disclosure by hypertensives was determined by a response style: disclosure was flexible and increased when situational pressure for accurate response increased. Thus, hypertensives prefer to withhold information. Normotensives had high levels of report whatever the situational context. The request to disclose was shown to have a potent dysregulatory effect on blood pressure for hypertensives only. Need for social approval was a possible underlying explanation for group differences. There are implications in these findings both for personality theory and therapy development. PMID- 2926701 TI - Cross-spouse correlates of blood pressure in hypertension-prone families in Utah. AB - This study used a subsample of 543 married couples from a large group of families in Utah, who were originally studied to assess the genetic and environmental determinants of hypertension. Excluding individuals on medication and controlling for the major risk factors for hypertension, evidence was obtained for cross spouse blood pressure associations equal in magnitude to self-psychosocial and demographic measures. Observed spouse-spouse similarity for blood pressures remained significant after adjustment for shared psychological factors. It is speculated that different aspects of each spouse's nonmarital environments (e.g. work, social support) have differential impacts on the marital environment and on physiologic indicators of health. PMID- 2926702 TI - Aspects of personality of soldiers presenting to an endoscopy clinic. AB - Eysenck Personality Questionnaires were completed by a consecutive series of 60 soldiers attending a military endoscopy clinic. Each individual was pair-matched with a non-endoscoped soldier from a medical ward and a soldier from the hospital alcohol treatment unit. Alcohol dependence and related disabilities were measured using the MAST, CAGE and SADQ questionnaires and liver function tests and MCV estimates were performed. Alcohol questionnaire scores and laboratory tests were analysed by discriminant function analysis and by applying 'cut-off' scores of the questionnaires. Analyses of the personality dimensions were carried out by analyses of variance and were examined in relation to sample, alcohol questionnaire scores and endoscopic findings. The soldiers from the alcohol treatment unit had the highest neuroticism score, followed by the soldiers attending the endoscopy clinic. Of the endoscoped soldiers, those diagnosed as non-ulcer dyspeptics had higher neuroticism scores than soldiers with ulcers. This finding was not associated with increased prevalence of alcohol dependence and related disabilities. PMID- 2926703 TI - Assessment of facial self-image by means of a distorting mirror and its relationship to personality. AB - A flexible distorting mirror was used to give a distorted image of volunteers, who then attempted to alter the mirror to give a true reflection of their faces. Their accuracy in performing this task was correlated with age, sex, extroversion, neuroticism and also with total body and facial self-image as obtained from questionnaires. On average, subjects could not accurately define the size of their faces to within 5 cm, and the higher the body image score on the questionnaire, the less well subjects performed on the flexible mirror. PMID- 2926704 TI - Teacher stress and health; examination of a model. AB - Stress in teaching derives from a variety of sources, and evidence exists linking such stress to physical and mental health concerns. Detailed examination of the linkages among personal factors, job stress, job satisfaction and symptomatology have not been done in this occupation, however, and the present study examines a model interrelating these variables. A survey of 245 predominantly female elementary school teachers in southeast Texas suggested that demographic factors and teaching background do not influence stress, satisfaction or health concerns. However, while job stress was the strongest predictor of job satisfaction, this stress had no direct relationship with health problems, an unexpected finding. Write-in responses by teachers indicated additional sources of stress, many of which were environmental or policy-based in nature. The implications of these findings for future research and stress management interventions for teachers are discussed. PMID- 2926706 TI - Establishing a nurse-client relationship. PMID- 2926705 TI - Cops & counselors. Counseling issues with prison inmate substance abusers. PMID- 2926709 TI - More on Billie Boggs. PMID- 2926708 TI - APNA or ANA? PMID- 2926707 TI - Incorporating Peplau's theory and case management. PMID- 2926710 TI - More on RCTs. PMID- 2926711 TI - The elderly widow: easing her role transition. PMID- 2926712 TI - Ethics of HIV testing. A personal view. PMID- 2926713 TI - A framework for taking a treatment history. PMID- 2926714 TI - Undergraduate occupational health teaching in British medical schools. PMID- 2926715 TI - The industrial toxicology of antimony. The Ernestine Henry lecture 1987. PMID- 2926716 TI - Fractured neck of femur. Prevention and management. Summary and recommendations of a report of the Royal College of Physicians. PMID- 2926717 TI - A syndrome resembling lymphomatoid granulomatosis in the dog. AB - Lymphomatoid granulomatosis (LYG) was diagnosed in seven dogs. Most of the affected dogs were young to middle-aged, and there was no breed or sex predilection. Basophilia was detected in six of the seven dogs. Radiographic abnormalities included lung lobe consolidation or pulmonary mass lesions, as well as abnormally large tracheobronchial lymph nodes. Histologic changes included angiocentric and angiodestructive pulmonary infiltrates characterized by large lymphoreticular and plasmacytoid cells as well as normal lymphocytes, eosinophils, and plasma cells. Five dogs were treated with combination chemotherapy, and three had a complete response to treatment. PMID- 2926718 TI - Radioactive iodine treatment of a functional thyroid carcinoma producing hyperthyroidism in a dog. AB - Radioactive iodine (131I) was used in the treatment of a 12-year-old female dog with hyperthyroidism resulting from a large, unresectable (and metastatic) thyroid carcinoma associated with signs of severe inspiratory stridor and dyspnea. Hyperthyroidism was diagnosed on the basis of clinical signs (polyuria, polydipsia, polyphagia, weight loss, nervousness) and high basal serum thyroxine (T4) concentrations, as well as thyroid radioiodine kinetic studies that showed a high radioiodine uptake into the thyroid (% thyroid uptake) and markedly increased serum concentrations of protein-bound iodine-131 (PB131I) after 131I tracer injection. Thyroid imaging revealed diffuse radionuclide accumulation by the tumor, which involved both thyroid lobes. The dog was treated with three large doses of radioiodine (131I), ranging from 60 to 75 mCi, given at intervals of 5 to 7 months. The dog became euthyroid, and the size of the tumor decreased by approximately 25% after each 131I treatment, improving the severe inspiratory stridor and dyspnea, but both the hyperthyroid state and breathing difficulty recurred within a few months of each treatment. The dog was euthanatized 5 months after the last treatment because of progressive tracheal compression and pulmonary metastasis. PMID- 2926720 TI - Factitious hyperkalemia in dogs with thrombocytosis. The effect of platelets on serum potassium concentration. AB - To determine the effect of platelet count on the accurate assessment of serum electrolyte concentrations, simultaneous platelet counts and electrolyte determinations were performed on serum and plasma from 40 dogs. Dogs were grouped according to platelet count as follows: thrombocytopenic (less than 150,000/microliters), normal (150,000 to 600,000/microliters), or thrombocytotic (greater than 600,000/microliters). Serum potassium concentration was significantly higher than plasma potassium concentration in normal dogs (mean difference, 0.63 +/- 0.17 mEq/l) and in dogs with thrombocytosis (mean difference, 1.55 +/- 0.73 mEq/l). This difference in potassium concentration between serum and plasma was positively correlated with platelet count (r2 = 0.86). In the blood of dogs with thrombocytosis, the serum-plasma potassium difference was further increased when the time period between blood collection and separation of serum or plasma from cells was lengthened. Differences between serum and plasma concentrations of sodium or chloride were not seen in any platelet group. These results suggest that a portion of the measured serum potassium concentration is released from platelets during the clotting process. In fact, profound elevations in serum potassium concentrations can occur factitiously in dogs with thrombocytosis. Therefore, the actual concentration of potassium in blood is determined more accurately by measuring the plasma concentration rather than the serum concentration of this electrolyte. PMID- 2926721 TI - Visual-evoked potential (VEP) methods and results in dogs. PMID- 2926719 TI - Thrombocytopenia associated with acute bovine virus diarrhea infection in cattle. AB - Thrombocytopenia was observed in 15 of 146 cases of clinically acute bovine viral diarrhea virus (BVDV) infection in adult cattle. Platelet counts ranged from 2,000 to 33,000/microliters. Clinically, a bleeding tendency was manifested by bloody diarrhea, petechial and ecchymotic hemorrhage, epistaxis, and abnormal bleeding from injection sites. Coagulation testing (six cases) gave no evidence of disseminated intravascular coagulation. Bone marrow aspirates were suggestive of active marrow necrosis (two cases) or recent repopulation (three cases). Treatment, when given, was supportive and empirical in nature. Six animals experienced complete clinical recoveries; the others died or were euthanatized. Although the pathogenesis of the thrombocytopenia was not definitively determined, thrombocytopenia associated with acute BVDV infection should be considered in the differential diagnosis for cattle with bleeding disorders. PMID- 2926722 TI - Sexually transmitted diseases profile of patients with chlamydial conjunctivitis. AB - During 1980-85, 1648 patients with conjunctivitis attended an Eye Hospital in Liverpool. Of these, 195 had proven chlamydial infection. On referral, only 68 adults and 27 children of this group, and 66 adults as 'contacts' attended the Sexually Transmitted Diseases Clinic. Screening tests detected a significant number of STD's among the adults. Though asymptomatic, a large proportion of them had chlamydia a potential pathogen, in their genital tract. The need for such a referral, full S.T.D. screening and appropriate systemic treatment to prevent some of the sequele of untreated chlamydial infection are emphasised. PMID- 2926723 TI - Rickettsia in the regiment. AB - A case of Rocky Mountain Spotted Fever (RMSF) is described, together with other cases of pyrexia whose occurrence originally gave the impression of a significant outbreak of the disease in a TA regiment after annual training in the USA. The role of the RMO is considered in such circumstances. PMID- 2926724 TI - Chronic giardiasis with vitamin B12 and folate deficiency presenting with psychiatric symptoms. PMID- 2926726 TI - Unde venimus et quo vademus? PMID- 2926725 TI - Heat-exercise hyperpyrexia. AB - A fatal case of "heat stroke" occurring on exercise in temperate conditions is described. Possible mechanisms for increased susceptibility are discussed and attention is drawn to a possible overlap with the malignant hyperpyrexia (MH) syndrome. The second day of strenuous exercise may be a time of special risk. More frequent consideration of dantrolene treatment in heat injury is suggested and the term "heat-exercise hyperpyrexia" is proposed to replace "heat stroke" and "exertional hyperpyrexia". PMID- 2926727 TI - The value of routine radiology in young psychiatric patients. AB - The current policy of obtaining routine skull and chest X-rays on all psychiatric admissions to military hospitals has been examined by scrutiny of the radiology reports on all such admissions during one calendar year. No clinically unexpected finding was demonstrated in any of the 352 patients so examined. Routine radiological investigation of these patients may safely be abandoned. PMID- 2926728 TI - Airborne resuscitation fluids. PMID- 2926729 TI - Robert the Bruce, King of Scots; the leprosy myth. PMID- 2926730 TI - All that wheezes is not asthma. PMID- 2926731 TI - Morale in battle--the medical and the military. PMID- 2926733 TI - Treatment of stage I endometrial carcinoma. AB - Cases of stage I endometrial carcinoma treated at Columbia-Presbyterian Medical Center, New York, between 1966 and 1980 were evaluated with regard to clinical parameters, surgicopathologic findings, treatment modalities and survival. Four factors significantly influenced survival: tumor grade, patient's age, uterine size and addition of postoperative external radiotherapy in cases of significant myometrial invasion or a poorly differentiated lesion. No deaths or significant morbidity resulted from the use of adjuvant whole pelvic radiation. PMID- 2926732 TI - Urethral syndrome. A comparison of different treatment modalities. AB - Sixty women with the diagnosis of urethral syndrome were consecutively assigned to one of three treatment modalities. The first group (20 patients) was treated with tetracycline, 2 g/d for ten days. The second group (20 patients) was treated with three serial urethral dilations at two- to three-week intervals, and the third group (20 patients) received placebo for ten days and served as a control group. A detailed clinical evaluation and uroflowmetry were performed before treatment and eight weeks afterwards. A subjective cure, which was defined as an absence of symptoms at the follow-up visits, was achieved in 20% of the placebo group, 50% of the tetracycline group and 75% of the urethral dilation group (P less than .01). An objective improvement in uroflowmetry occurred only in the group treated with serial urethral dilation. PMID- 2926734 TI - Acute puerperal uterine inversion. New approaches to management. AB - A retrospective review identified 56 patients with uterine inversion, from July 1977 through June 1986, from weekly obstetric statistics, delivery records and computerized discharge diagnoses. All patients underwent delivery by house officers, midwives or medical students under supervision. An analysis of the data revealed that the risk factors were primiparity, a fundally implanted placenta and delivery of a macrosomic fetus. Also, patients who received oxytocin with or without MgSO4 were at higher risk of puerperal inversion. MgSO4 by itself did not appear to be a risk factor. A placenta attached at the time of inversion appeared to have a protective effect against the development of shock. The use of betamimetics or MgSO4 appeared to be an acceptable alternative to general anesthesia in relaxing the uterus and aiding in its repositioning. Those agents were more likely to be successful in acute cases than in subacute ones and in second-degree inversion than in third-degree. PMID- 2926735 TI - Adenocarcinoma in a mature cystic teratoma. A case report. AB - A mucin-producing adenocarcinoma arose in a well-differentiated, mature, cystic teratoma. The patient underwent a total abdominal hysterectomy, left salpingo oophorectomy, omentectomy and paraaortic lymph node biopsy. The prognosis is unfavorable when the tumor extends through the cyst wall and involves intraperitoneal structures. PMID- 2926736 TI - Isolated torsion of the uterine tube in pregnancy. A case report. PMID- 2926737 TI - Changes in the surgical management of early breast cancer in England. AB - A questionnaire survey of consultant surgeons in England indicates that there has been a considerable change in opinion over the past few years concerning the management of early breast cancer; only 39.1% would now perform mastectomy, whereas 64.4% would perform conservative surgery. The most common forms of management are simple mastectomy and axillary clearance (21.9%); wide excision, axillary clearance plus radiotherapy (20.1%); and wide excision plus radiotherapy alone (16.9%). The majority of the surgeons would offer patients a choice of surgery, but only 52% had access to a breast care nurse. PMID- 2926738 TI - Liaison psychiatry in a breast cancer unit. AB - The first 50 referrals to a newly established liaison psychiatry service for the breast cancer unit at Guy's Hospital, London, have been examined. The majority of referrals were for psychological reactions to malignant disease, most of these were mood disturbances. Patients with sustained psychological reactions to their malignant disease were more likely to have had treatment for previous psychiatric illness and to lack a confiding relationship compared with those whose psychological reactions were transient. Teaching doctors and nurses to deal effectively with the transient psychological reactions of patients to their malignant disease is an important task of liaison psychiatry. PMID- 2926739 TI - Differences in health, knowledge and attitudes between vegetarians and meat eaters in a random population sample. PMID- 2926740 TI - Renal angiomyolipoma: a comparison of 5 cases diagnosed by CT scan. PMID- 2926741 TI - Adenocarcinoma of the appendix. AB - Patients presenting with adenocarcinoma of the vermiform appendix at the Royal Preston and Chorley District General Hospitals were reviewed for the 15 year period 1972-1986. Eleven cases were identified, representing a rate of 1 in 956 for all appendicectomies performed. A third of the cases presented as acute appendicitis. However, of 8 patients who initially had an appendicectomy, only 4 subsequently underwent further surgery (right hemicolectomy). One patient died of recurrent disease. Five of the patients presenting were under 60 years of age. During the same period, the total number of appendicectomies performed annually declined by 50%. The study highlights the need to subject all appendicectomy specimens to histological examination, and that the disease presents in a younger age group than commonly seen for malignant colonic neoplasms. PMID- 2926742 TI - Psychological welfare of patients with breast cancer. PMID- 2926743 TI - Conjunctival xerosis in cystic fibrosis. PMID- 2926744 TI - Emphysematous pyelonephritis. PMID- 2926745 TI - Folate deficiency due to giardiasis. PMID- 2926746 TI - Occult Leydig cell testicular tumour presenting with gynaecomastia. PMID- 2926747 TI - The treatment of atrial flutter with high-dose amiodarone. PMID- 2926748 TI - Spontaneous rupture of phaeochromocytoma mimicking leaking aortic aneurysm. PMID- 2926749 TI - Jejunocolic fistula after radiation for malignant teratoma. PMID- 2926750 TI - Managing the dyspeptic patient. PMID- 2926751 TI - Nephrotic syndrome as the marker for underlying malignancy. PMID- 2926752 TI - Management of the solitary thyroid nodule. PMID- 2926753 TI - The National Health Service--a grand design in distress. PMID- 2926754 TI - Vascular compression in thoracic outlet syndrome. PMID- 2926755 TI - Congenital erythropoietic porphyria and congenital adrenal hyperplasia with evidence for hepatic delta-5 alpha-reductase deficiency. PMID- 2926756 TI - Congenital skin defects, twins and toxoplasmosis. PMID- 2926757 TI - Precision excision of pulmonary metastases--a useful technique. PMID- 2926758 TI - Mycosis fungoides of the central nervous system. PMID- 2926759 TI - Hepatic and splenic conservation in trauma. PMID- 2926760 TI - AIDS and drug addiction needle exchange schemes. PMID- 2926761 TI - Ehlers-Danlos syndrome with infarction of stomach. PMID- 2926762 TI - Superficial siderosis of the central nervous system. PMID- 2926763 TI - Mental symptoms presenting in pheochrompcytoma. PMID- 2926764 TI - Diving: occupation or physiological experiment? PMID- 2926765 TI - Which inhaler is best? PMID- 2926766 TI - Multicultural aspects of child abuse in Britain. PMID- 2926767 TI - Morale in battle--the medical and the military. PMID- 2926768 TI - Long-term sequelae of diving. PMID- 2926769 TI - 'Benign thoracic pain' syndrome: role of magnetic resonance imaging in the detection and localization of thoracic disc disease. AB - The syndrome of 'benign thoracic pain' is seen in young women who have pain and tenderness in the mid-thoracic spine radiating around the chest and aggravated by spinal movement. Ten consecutive patients with this syndrome and 15 controls were evaluated with magnetic resonance imaging (MRI). This showed thoracic intervertebral disc dehydration with no associated prolapse in 90% of the patients and 13% of the controls. We postulate that the clinical features are due to impaired shock absorption of these degenerate discs rather than direct compression of surrounding structures. MRI is non-invasive and does not use ionizing radiation; it allows direct visualization of the entire thoracic spine and cord, and accurate detection of early disc degeneration. Thus, it is the imaging modality of choice for defining the subtle intervertebral disc abnormalities that characterize the 'benign thoracic pain' syndrome. PMID- 2926770 TI - Magnetic resonance imaging of the nose and paranasal sinuses. AB - Seventy-five patients with a wide range of sinus disease have been investigated by magnetic resonance (MR): these included congenital conditions, allergic and inflammatory sinus disease, fungus infections, and the necrotizing granulomata. In addition, a variety of benign and malignant tumours have been examined, and in the more recent sinus malignancies the paramagnetic contrast agent, Gadolinium (Gd) DTPA (Schering Health Care) has been used. This experience of magnetic resonance scanning has shown that it is superior to computed tomography in demonstrating the extent of malignant disease in the nose and sinuses; most especially when Gd DTPA is used, reaching an accuracy of over 96% by biopsy correlation. An additional advantage of this technique is the wide coverage of the head and neck for the assessment of malignant disease, provided by direct 3 plane imaging and the multislice facility. The main disadvantage of magnetic resonance of the sinuses is the poor demonstration of calcification and bone. For this reason the MR scans may need to be augmented by high resolution CT performed specifically to show bone detail. PMID- 2926771 TI - Human rectosigmoid electromyography: a new approach and some pitfalls. AB - A method has been developed to record directly myoelectrical activity from the smooth muscle of the colon of intact subjects using pairs of intramuscular wires. Discrete bursts of myoelectrical activity occurred at 4-20 per min. A small interelectrode distance in this method allows contamination of colonic myoelectrical activity by the electromyogram of skeletal muscle to be excluded. This artefact has not been considered in previous recordings of 'colonic' activity. PMID- 2926772 TI - Kuru, AIDS and unfamiliar social behaviour--biocultural considerations in the current epidemic: discussion paper. PMID- 2926773 TI - Population ecology of preimaginal Culex tarsalis (Diptera: Culicidae) in Kern County, California. AB - The effects of abiotic and biotic mortality factors on preimaginal survivorship and the production of adults were investigated for populations of Culex tarsalis Coquillett at a stable foothill breeding site during 1985 and at seven ephemeral breeding sites during 1986. Female abundance was correlated temporally with larval abundance and spatially with first instar to adult survivorship. Catastrophic events, such as fluctuations in water level and pollution, drastically reduced larval and pupal abundance. Under relatively stable conditions, the effect of natural mortality factors was estimated by comparing preimaginal survivorship rates, estimated horizontally for fed and unfed cohorts in predator exclusion cages, with survivorship, estimated vertically from the age structure of the natural population using a life table approach. Mortality for fed cohorts ranged from 8.5 to 90.0% and was attributed to abiotic factors, including temperature and water quality. Mortality caused by lack of food was comparatively low (less than 15%); however, the low nutrient level at three of six sites lengthened the duration of the fourth stadium, delayed pupation, and resulted in the emergence of small-sized adults with a reduced expression of autogeny. Predation mortality ranged from 3.7 to 84.5% and was the most important cause of larval death at five of six study sites. Based on relative abundance and correlation over time and space, zygopteran naiads were the most important predator at a stable foothill breeding site during 1985, and coleopteran larvae were the most important predator at ephemeral breeding sites sampled during 1986. PMID- 2926775 TI - Blood-feeding drive inhibition of Aedes sierrensis (Diptera: Culicidae) induced by the parasite Lambornella clarki (Ciliophora: Tetrahymenidae). AB - Female Aedes sierrensis (Ludlow) infected with the parasitic ciliate Lambornella clarki Corliss and Coats were significantly less responsive toward a human host than uninfected females. The proportion of infected females that were inhibited in host-seeking and blood-feeding remained high in all daily exposures to the host. Those that did respond took approximately twice as long to land on the host and 25% longer to complete probing as did uninfected females. In contrast, nearly all uninfected females more than 5 d old rapidly responded to and blood fed on the host. Uninseminated females were more similar in their behavior to infected females than to uninfected inseminated females. For females allowed to ingest blood, the time from completion of probing to engorgement was not significantly different for infected versus uninfected females. Some blood-fed, uninfected females took one additional small blood meal 1-3 d after the first blood meal, but most (56%) were inhibited in blood feeding until after ovipositing. Overall feeding time and most sequential behaviors associated with blood feeding were similar to those reported for other mosquito species. Parasite-induced inhibition of the blood-feeding drive may explain low capture rates of L. clarki-infected mosquitoes at human bait. PMID- 2926776 TI - Evaluating mite (Acari) allergenicity of house dust by guanine quantification. AB - The development of a quick color reaction for guanine in house dust has made it possible to screen many homes for mite products of allergenic consequence. The azo dye methods are specific enough to be useful for the development of a sanitary standard. Comparing the guanine quantification results with mite counts and determinations of the mite antigen P1 (Der p I) leads to the conclusion that the provisional standard for mattress dust of 0.6 mg guanine/g dust can be extended to dust from floor coverings and padded furniture, at least in western Europe. Below this level, the sensitization risk to patients allergic to house dust mites seems to be minimal. PMID- 2926774 TI - Comparison of the isozyme phenotypes of the morphologically similar ticks Amblyomma cajennense and A. imitator (Acari: Ixodidae) from south Texas. AB - A survey of Amblyomma Koch tick populations in southern Texas revealed that A. imitator Kohls was restricted to the two most southern counties, but that A. cajennense (Fabricius) ranged at least as far north as Kingsville, Tex. Females of the two species could be distinguished by the presence of chitinous tubercles on the festoons of A. cajennense and the presence of projections over both sides of the apron of the genital aperture in A. imitator. Males were distinguished by size, ornamentation, and the elongate ventral scutes of A. imitator. In addition, six enzymes, AATA, ACONA, IDH2, LDH, MPI, and PEP, were diagnostic for the two species and two others, aGPD and ACONC, had high diagnostic values. Resulting interspecific divergence was significant, I = 0.582. Genetic variability was higher in A. imitator (h = 0.092) than in A. cajennense (h = 0.057), but neither species exhibited marked interpopulation divergence (I = 0.991 in A. imitator, I = 0.994 in A. cajennense). PMID- 2926777 TI - Computer simulation of population dynamics of the American dog tick (Acari: Ixodidae). AB - A comprehensive computer model was developed for simulation of the population dynamics of the American dog tick (ADT), Dermacentor variabilis Say, in North America. The model simulates the effects of major environmental variables, such as ambient temperature, saturation deficit, kind of habitat, and host density, on ADT population dynamics in ecosystems with small mammals as hosts for immature ticks and medium-sized mammals or domestic dogs as hosts for adult ticks. General validity of the model was established by comparisons between simulated and actual population densities for a series of years at locations in Virginia, Maryland, and Massachusetts using actual weekly weather data for each year as a model input. Using historical-average weather data for 11 locations within the known geographic range of ADT and 3 locations outside this range, the model produced acceptable values for initial population growth rate and generation time, as well as realistic equilibrium population densities and seasonal activity patterns. This model can be used as a framework for additional modeling efforts to simulate the transmission of Rocky Mountain spotted fever and to study various strategies for management of ADT populations. PMID- 2926778 TI - Physiological phases of nymphal molting defined by mobility, body weight decrease, and excretion in Haemaphysalis longicornis (Acari: Ixodidae). AB - Based on the rate of body weight decrease, the nymphal premolting period in Haemaphysalis longicornis Neumann was divided into three phases: a period of rapid weight decrease following detachment, a period of slight decrease, and another period of relatively rapid decrease before molting. Phase 1 was characterized by increased guanine excretion and mobility. The rate of weight decrease during phase 1 was greater in males than in females. During the premolting period, excreta consisted only of guanine and were devoid of hematin. In phases 2 and 3, neither excretion nor mobility was observed. Twenty-eight percent of the females and 40% of the males did not undergo phase 3. Adult body weight decreased rapidly until about day 5 after molting, after which weight was maintained until the end of the experiment. Guanine was excreted in large quantities just after molting and in small amounts for 4 d thereafter. Hematin excretion followed guanine excretion and was concentrated in a 3-d period starting 4 d after molting. The beginning of hematin excretion coincided approximately with the point at which body weight was maintained at a constant state. There were no quantitative differences per unit of body weight between the sexes with the exception of the rate of body weight loss during nymphal phase 1. PMID- 2926779 TI - Ontogeny of Rhyncoptes grabberi, n. sp. (Acari: Astigmata: Rhyncoptidae) associated with Macaca mulatta. AB - All ontogenetic stages of a new species of follicle mite, Rhyncoptes grabberi, n. sp., associated with rhesus monkeys, Macaca mulatta, are described and illustrated. The ontogeny of the new species is characterized by numerous retardations and losses of ancestral transformations, especially in the female developmental line. In the male developmental line, many transformations are delayed to the male itself. PMID- 2926780 TI - Limited autonomy and partnership: professional relationships in health care. AB - Principles of autonomy and self-determination have been upheld as vital to modern day medical and ethical practice. However, the complexities of current health care and changes in the expectation of some patients and their families justify a review of such concepts. Their limitations and relativities may suggest that other descriptions of partnership and negotiated goal-setting, while based on respect for autonomy, reflect more modern and ideal multi-disciplinary practices. Discussion should extend beyond the 'classic' participants of patient and doctor to a more realistic picture where other health carers are included. It is therefore apposite that other professional relationships are considered as they affect areas of doctors' and patients' responsibilities. Such partnership between members of the team may not be without problems and conflict, but the principle of negotiated agreements could result in more long-term harmony, and greater patient welfare. PMID- 2926781 TI - Organ donations should not be restricted to relatives. AB - Should we remove whole organs from living donors only in the case where they are genetically related to the intended recipients of such organs? The practice in a majority of European nations is to apply such a restriction. Yet this restriction obviously limits the availability of already scarce donor organs, and curtails the opportunities for altruistic action on the part of those who, in any given case, are not genetically related to the recipient. The author argues that we have a duty to maximise procurement of organs, and that we should respect the 'genetic relative' restriction only in response to compelling moral reasons. The author considers the principal objections to non-related donation and shows them to be misdirected. He concludes that non-related donation should be welcomed where clinically appropriate and truly voluntary. PMID- 2926782 TI - To tell or not to tell the diagnosis of schizophrenia. AB - Some patients with schizophrenia are not told their diagnosis. The moral, clinical and practical issues involved in telling or not telling the patient are discussed. In some cases a relative is told the diagnosis but not the patient. The implications for the family and clinical outcome are outlined. A case history illustrating some of these issues is presented. PMID- 2926784 TI - Which of two individuals do you treat when only their ages are different and you can't treat both? AB - A relative value of life dependent on age has been produced from a survey of 721 randomly selected individuals together with other observations of professional practice. The results are presented in diagrammatic form. If two identical people, except for age, present for medical treatment for a life-threatening condition and only one can be treated then the diagram indicates what the choice should be. PMID- 2926783 TI - The moral status of the near-term fetus. PMID- 2926786 TI - Voluntarism and realism in medieval ethics. AB - In contrast to other articles in this series on the history of moral philosophy the present essay is not devoted to expounding the views of a single author, or to examining a particular moral theory. Instead it discusses an important dispute between two medieval accounts of the relation between theological and moral propositions. In addition to its historical interest this debate is important both because it connects earlier and later ethical thought--being influenced by Greek moral theories and influencing subsequent European philosophy--and because it concerns issues that remain important to philosophers and to those who claim that their ethical beliefs are dictated by religious convictions. PMID- 2926785 TI - The importance of listening to medical students' experiences when teaching them medical ethics. AB - This paper describes the change of emphasis that occurred in the teaching of ethics to small groups of clinical students. Although the original focus of the course was on the analysis of ethical dilemmas associated with individual patients known to the students, it soon became evident that there were, for the students themselves, more fundamental ethical dilemmas in their new role as clinical students. These included worries about how to respond when patients asked questions which their consultants had previously deceived them about, worries about inflicting pain on patients, as with intravenous cannulation, and the role of the medical student in the clinical team. We emphasise the need to explore student experiences as part of the process of ethics teaching. PMID- 2926787 TI - Euthanasia, letting die and the pause. PMID- 2926788 TI - The myth of informed consent: in daily practice and in clinical trials. AB - Until about thirty years ago, the extent of disclosure about and consent-seeking for medical interventions was influenced by a beneficence model of professional behaviour. Informed consent shifted attention to a duty to respect the autonomy of patients. The new requirement arrived on the American scene in two separate contexts: for daily practice in 1957, and for clinical study in 1966. A confusing double standard has been established. 'Daily consent' is reviewed, if at all, only in retrospect. Doctors are merely exhorted to obtain informed consent; they often minimise uncertainties about 'best' treatment and they feel duty-bound to provide patients with an unequivocal recommendation for action. 'Study consent' in a clinical trial is reviewed prospectively, and doctors are compelled by regulation to point out that there is insufficient evidence to make a rational choice between two compared treatments. It has been impossible to devise informed consent practices that satisfy, in full, the competing moral imperatives of respect for autonomy, concern for beneficence with emphasis on the value of health, and a vigil for justice. A way must be found to experiment with various discretionary approaches that would strike a realistic balance among competing interests. PMID- 2926789 TI - Enterotoxin production by Staphylococcus aureus isolates from cases of septicaemia and from healthy carriers. AB - In a prospective study, 52 Staphylococcus aureus isolates from individual patients with septicaemia and 27 nasal strains from separate, healthy carriers were compared for production of a range of extracellular proteins and toxins. Whereas there was no difference (p greater than 0.05) between septicaemic and nasal isolates with respect to incidence of alpha, beta, gamma and delta haemolysins, toxic shock syndrome toxin-1 or staphylokinase production, the incidence of enterotoxin A, B, and C production was higher among isolates from septicaemia (p less than 0.01). Of the isolates from septicaemia, 33 (63%) produced enterotoxins A, B, C or D alone or in combination. Only three (11%) of the nasal isolates produced a single enterotoxin, enterotoxin D. Of the isolates from septicaemia, 67% were hospital-acquired and greater than 25% of these were endemic, methicillin-resistant (MRSA) strains. All MRSA strains produced either enterotoxin A, or enterotoxin B, or both. These findings suggest a possible role for enterotoxins in the pathogenesis of S. aureus disease other than food poisoning. PMID- 2926790 TI - Phagocytosis and ingestion of influenza virus by human polymorphonuclear leucocytes in vitro: electronmicroscopy studies. AB - Interaction of human polymorphonuclear leucocytes (PMNL) and influenza virus (IFV) was studied in vitro. At 0 degree C, the viral particles were bound extensively to the surface of the PMNL membrane with a ratio of about 1000 virus particles to a single PMNL. The binding was sensitive to neuraminidase, suggesting attachment through sialo-compound receptors. At 37 degrees C, the virus particles disappeared rapidly from the cell surface, about half of them being eluted and the remainder being endocytosed into the cytoplasmic vesicles. Immuno-gold electronmicroscopy suggests that the virus particles are ingested into phagosomal vesicles and lysed. PMID- 2926791 TI - Genetic evidence for a chromosomally integrated multiresistance plasmid in Salmonella dublin. AB - Of 1099 isolates of Salmonella dublin during 1985-86, 11 (1%) were resistant to three or more antibiotics. Strain S4659/85, a multiresistant isolate, lacked autonomous R plasmids but showed incompatibility with incH2 plasmids and donated resistance determinants in matings. Transconjugants acquired incomplete R plasmids which integrated stably into a specific chromosomal site. These data provide an insight into the behaviour of R plasmids in S. dublin. PMID- 2926792 TI - Formation of methylglyoxal by bacteria isolated from human faeces. AB - Bacteria present in the human gut may produce methylglyoxal--a cytotoxic substance in mammals. This was investigated by studying the activity of methylglyoxal synthase, which produces methylglyoxal from dihydroxyacetone phosphate, and methylglyoxal concentration in growth medium of various bacteria isolated from human faeces. Facultative and strictly anaerobic bacteria isolated from faeces were able to produce methylglyoxal in both defined and complex media. Proteus spp. produced large amounts of methylglyoxal and had the greatest methylglyoxal synthase activity. Supplementing defined medium for facultative anaerobes with glucose 1% w/v did not significantly alter enzyme activity or methylglyoxal production. Inclusion of short chain fatty acids or bile acids in the medium reduced methylglyoxal synthase activity and methylglyoxal production by Proteus spp. None of the organisms examined had amine oxidase activity which could have contributed to methylglyoxal production from aminoacetone. PMID- 2926793 TI - Recovery of spores of Clostridium difficile altered by heat or alkali. AB - The effect of heating or alkali-treatment on spore recovery in ordinary growth medium was examined for four strains of Clostridium difficile. Heating spores at 80 degrees C for 10 min produced 95.50-99.95% decreases in the recovery rates. Treatment with 0.1 N NaOH for 15 min produced 99.47 and 99.83% decreases in spore recovery rates for two of the four strains. The influence of either addition of lysozyme after treatment with sodium thioglycollate (thioglycollate-lysozyme method) or addition of sodium taurocholate (taurocholate method) on recovery of heat- or alkali-treated C. difficile spores was also examined. Viable spores of all strains altered by heating at 90 degrees C or 100 degrees C for 10 min could not be recovered at all by the taurocholate method. Nor did this method allow recovery of alkali-altered spores treated with greater than 0.2 N NaOH for 15 min. On the other hand, 10-47% of altered spores heated at 90 degrees C for 10 min were recovered by the thioglycollate-lysozyme method, and alkali-altered spores treated with 0.1-0.3 N NaOH for 15 min were as completely recovered by this method as untreated spores. These results indicate that the thioglycollate lysozyme method is more effective than the taurocholate method for recovery of the heat- or alkali-altered C. difficile spores. PMID- 2926794 TI - A pyrolysis mass spectrometry study of fusobacteria. AB - Strains of fusobacteria (143) were examined by pyrolysis mass spectrometry (Py MS) with a Horizon Instruments PYMS 200X. Fusobacterium necrogenes, F. necrophorum, F. nucleatum, F. mortiferum, F. varium, F. gonidiaformans, F. naviforme, F. russii and Leptotrichia buccalis were discriminated. Strains of fusobacteria isolated from tropical ulcers, although similar to F. mortiferum in conventional tests, were discriminated from each of these species in Py-MS. Identification of 416 spectra to species level agreed with conventional bacteriological methods in 91.8% of cases, was equivocal in 3.4% and disagreed in 4.8%. Classification based on pyrolysis data resolved groups largely corresponding to the recognised species. However, F. nucleatum strains were divided between two distinct groups. The tropical ulcer strains were resolved as a distinct homogeneous group. Py-MS is a rapid, inexpensive and convenient procedure for characterisation of bacteria, with the capacity for a high throughput of samples, although the initial cost of the apparatus is high. PMID- 2926795 TI - Habituation of optically evoked blink reflex in mentally retarded adults. AB - This study was done to record the difference in habituation patterns of optically evoked blink reflexes in mentally retarded and normal adults. Sets of photic stimuli with fixed interstimulus duration were utilized in normal volunteers and mentally retarded adults. The interstimulus duration decreased with each sequential set. The blink responses were recorded on fibreoptic recording paper. These electrophysiological methods show objectively that the blink responses to light which habituate in normal adults fail to do so in those who are mentally retarded. PMID- 2926796 TI - Hospital to community: a pilot rehabilitation project for elderly mentally retarded. AB - Four mentally handicapped patients, three of whom were aged 75 years plus, with a mean age of 67 years (in 1981) and a total institutional life of 160 years, have been successfully rehabilitated in a group home in an active community community environment since August 1981. The process of preparing them for independent living, the social services and community nursing support need, the qualitative change in their life style are described. The success is defined as a fuller community integrated living, free of institutional rigidity and freedom to do what they like with some support and using all the community services as used by other people. PMID- 2926798 TI - Prevalence of dyskinesia and related movement disorders in a developmentally disabled population. AB - The prevalences and inter-relationships of five types of movement disorders were evaluated in a large, developmentally disabled (DD) population (n = 1227); prevalence was evaluated with regard to severity, age, gender and antipsychotic drug (APD) exposure. Dyskinesia was found in 48% of the sample, dystonia in 29%, akathisia in 13%, Parkinsonism in 3% and paroxysms in 4%. Many persons had more than one symptom so that 72% had one or more of the five target symptoms. Although the five movement-disorder categories were not mutually exclusive, analysis supported the individuality of the categories as defined in this study. The prevalences of dyskinesia and Parkinsonism were considerably greater than those in the general population. On the other hand, the prevalence of dyskinesia was similar to that reported for psychiatric and institutionalized geriatric populations. Parkinsonism increased with age and male gender, while dyskinesia increased with age and female gender. APD-exposure was significantly correlated only with akathisia. PMID- 2926797 TI - The effects of stereotyped behaviour on orienting and tonic cardiac activity. AB - The relationship of cardiac activity to stereotyped behaviour was studied in profoundly mentally retarded persons, using both inter-group comparisons. The first intra-group comparison involved examining the relative magnitude of an orienting response to an auditory stimulus during the occurrence or nonoccurrence of stereotyped body rocking. While no differences were found between periods of rocking and non-rocking when behavioural measures of orienting were used, smaller changes in post-tone heart rate were observed during periods of stereotyped rocking. A second intra-group comparison found that stereotyped behaviour was associated with a significant increase in heart rate but no change in heart rate variability when compared to periods of no stereotyped activity. Finally, using an inter-group comparison, individuals who displayed stereotyped body rocking exhibited higher tonic heart rates and lower heart rate variability during periods of no stereotyped behaviour than was observed in matched control subjects. This result suggests that stereotyped behaviour may be correlated with reduced vagal tone. PMID- 2926799 TI - The use of drugs for physical conditions in adults with mental retardation. AB - A survey of the drugs given for physical complaints in two mental handicap hospitals is described. Thirty-six per cent of 537 adults in hospital A and 43% of 944 adults in hospital B received medications and, of those who did, over half in each hospital received only one drug. The hospital populations differed significantly but both showed a significant increase in total drug usage with increasing age in both sexes, higher among females in every group. This increase was greatest with C.V.S. drug usage, but it did not reach significance for the three most frequently prescribed groups, which were gastrointestinal drugs (to 13% of the total patients), vitamins and nutritional supplements (11%), dermatological (10%) and cardiovascular (10%) drugs. Mental level was significantly indirectly related to usage of gastrointestinal drugs, drugs for anaemia, and vitamins and nutritional supplements, and directly to usage of cardiovascular drugs. PMID- 2926800 TI - Post mortem findings in a patient with 46,XX,fra(2)(q13). AB - A severely mentally retarded girl who suffered from grand mal seizures, myoclonic jerking and ataxia died at 18 years of age. Chromosome studies, before and after death revealed a fragile site on chromosome 2q13, the expression of which was greater in peripheral blood than in fibroblasts on two occasions. Post mortem findings did not reveal any abnormality which could be attributed to this fragile site. PMID- 2926801 TI - Transcervical resection of submucous uterine fibroids: an alternative approach to management. AB - Transcervical resection of submucous uterine fibroids can be an effective alternative to laparotomy and transuterine myomectomy in selected women. To date the authors have performed this procedure in three patients in an ambulatory environment. In two patients, transcervical resection was performed for giant intrauterine myomas which caused pathologic uterine bleeding and infertility. In a third patient the procedure was performed to resect multiple small submucous myomas causing infertility. PMID- 2926802 TI - Binding stoichiometry and structure of RecA-DNA complexes studied by flow linear dichroism and fluorescence spectroscopy. Evidence for multiple heterogeneous DNA co-ordination. AB - The interaction between RecA and DNA (in the form of unmodified single-stranded DNA, fluorescent single-stranded DNA and double-stranded DNA) is studied with linear dichroism and fluorescence spectroscopy. RecA is found to form a complex with single-stranded DNA with a binding stoichiometry of about four nucleotides per RecA monomer, in which the DNA bases appear to have a random orientation. Addition of ATP gamma S (a non-hydrolyzable analog of ATP) reduces the stoichiometry to about three nucleotides per RecA and causes the DNA bases to adopt an orientation preferentially perpendicular to the fiber axis. This complex can incorporate an additional strand of single-stranded DNA or double-stranded DNA, yielding a total stoichiometry of six nucleotides or three nucleotides and three base-pairs, respectively, per RecA. RecA, in the presence of ATP gamma S, is also found to interact with double-stranded DNA, with a stoichiometry of about three base-pairs per RecA. In all studied complexes, the tryptophan residues in the RecA protein are oriented with their planes preferentially parallel to the fiber axis, whereas in complexes involving ATP gamma S the planes of the DNA bases are oriented preferentially perpendicular to the fiber. This virtually excludes the possibility that the tryptophan residues are intercalated in the DNA helix. On the basis of these results, a model for the research of homology in the RecA-mediated, strand-exchange reaction in the genetic recombination process is proposed. PMID- 2926803 TI - Structure of the amino-terminal domain of phage 434 repressor at 2.0 A resolution. AB - The crystal structure of the amino-terminal domain of phage 434 repressor has been solved using molecular replacement methods and refined to an R-factor of 19.3% against data to 2.0 A resolution. The protein comprises five short alpha helices. Two of these form a helix-turn-helix motif, very similar to those found in related proteins. The protein is remarkably similar to the Cro protein from the same phage. PMID- 2926805 TI - Visualization of alpha-helices in tobacco mosaic virus by cryo-electron microscopy. AB - We have used tobacco mosaic virus (TMV) as a test specimen, in order to develop techniques for the analysis of high-resolution structural detail in electron micrographs of biological assemblies with helical symmetry. It has previously been shown that internal details of protein structure can be visualized by processing electron micrographs of unstained specimens of extended two dimensional crystalline arrays. However, the techniques should in principle be applicable to other periodic specimens, such as assemblies with helical symmetry. We show here that data to spacings better than 10 A can be retrieved from electron images of frozen hydrated TMV. The three-dimensional computed map agrees well with that derived from X-ray diffraction and shows the two pairs of alpha helices forming the core of the coat subunit, the C alpha-helix and the viral RNA. The results demonstrate that it is possible to determine detailed internal structure in helical particles. PMID- 2926804 TI - Energy of stabilization of the right-handed beta alpha beta crossover in proteins. AB - An explanation in terms of conformational energies is provided for the observed nearly exclusive preference of the beta alpha beta structure for forming a right handed, rather than a left-handed, crossover connection. Conformational energy computations have been carried out on a model beta alpha beta structure, consisting of two six-residue Val beta-strands and of a 12-residue Ala alpha helix, connected by two flexible four-residue Ala links to the strands. The energy of the most favorable right-handed crossover is 15.51 kcal/mol lower than that of the corresponding left-handed cross-over. The right-handed crossover is a strain-free structure. Its energy of stabilization arises largely from the interactions of the two beta-strands with one another and with the alpha-helix. On the other hand, the left-handed crossover is either disrupted after energy minimization or it remains conformationally strained, as indicated by an energetically unfavorable left twisting of the beta-sheet and by the presence of high-energy local residue conformations. In the energetically most favorable right-handed crossover, the right twisting of the beta-sheet and its manner of interacting with the alpha-helix are identical with those computed earlier for isolated beta-sheets and for packed alpha/beta structures. This result supports a proposed principle that it is possible to account for the main features of frequently occurring structural arrangements in globular proteins in terms of the properties of their component structural elements. PMID- 2926806 TI - Crystallization and preliminary X-ray study of horse pancreatic lipase. AB - Horse (Equus caballus) pancreatic lipase (EC 3.1.1.3) has been crystallized using the hanging drop method of vapour diffusion at 20 degrees C. The best crystals were grown from an 8 mg/ml solution in 10 to 20% (w/v) polyethylene glycol 8000, 10 mM-MgCl2, 0.1 M-NaCl, 0.1 M-Mes buffer (pH 5.6). They reach dimensions of 0.8 mm x 0.4 mm x 0.6 mm. X-ray examination of the lipase crystals shows that they are orthorombic with a space group P2(1)2(1)2(1). Their cell dimensions are a = 79.8 A, b = 97.2 A c = 145.3 A. Two molecules per asymmetric unit give a Vm value of 2.82 A3/dalton (56% water content). Lipase crystals strongly diffract to at least 1.8 A resolution. Some molecular properties of horse lipase compared to those of the better-known porcine enzyme are also presented. PMID- 2926807 TI - Does titin regulate the length of muscle thick filaments? AB - The protein titin has been localized by electron microscopy of myofibrils labelled with monoclonal antibodies. The data are consistent with individual titin molecules extending from near the M-line to beyond the ends of thick filaments, a distance of approximately 1 micron. In the A-band, titin appears to be bound to thick filaments, probably to the outside of the filament shaft. Molecules of titin in this configuration provided an obvious mechanism by which the length of thick filaments could be regulated accurately. PMID- 2926808 TI - Nucleotide sequence of the BALB/c mouse beta-globin complex. AB - The nucleotide sequence of 55,856 base-pairs containing all seven beta-globin homologous structures from chromosome 7 of the BALB/c mouse is reported. This sequence links together previously published sequences of the beta-globin genes, pseudogenes and repetitive elements. Using low stringency computer searches, we found no additional beta-globin homologous sequences, but did find many more long interspersed repetitive sequences (L1) than predicted by hybridization. L1 is a major component of the mouse beta-globin complex with at least 15 elements comprising about 22% of the reported sequence. Most open reading frames greater than 300 base-pairs in the cluster overlap with L1 repeats or globin genes. Polypurine, polypyrimidine and alternating purine/pyrimidine tracts are not evenly dispersed throughout the complex, but they do not appear to be excluded from or restricted to particular regions. Several regions of intergenic homology were detected in dot-plot comparisons of the mouse sequence with itself and with the human beta-globin sequence. The significance of these homologies is unclear, but these regions are candidates for further study in functional assays in erythroid cell lines or transgenic animals. PMID- 2926809 TI - Organization of a gene family developmentally regulated during Dictyostelium discoideum spore germination. AB - mRNA specific to cDNA clone pLK109 is present in Dictyostelium discoideum spores, increases about two- to threefold at 0.5 to 1 h during spore germination, and then rapidly decreases. The mRNA is not detectable in vegetative cells or in early multicellular development on filters, but is present late during development, approximately at the time of sporulation. 109 mRNA in spores is 700 nucleotides in length but this is processed during germination by shortening of the poly(A) tail to about 600 nucleotides at 1 to 1.5 hours. pLK109 is a member of a multigene family containing three separate genes, and we have isolated and sequenced all of them. All three sequences code for deduced proteins of 127 amino acid residues, with only a few amino acid differences among them. Gene 1 represents the "transcribed" gene, since all 33 cDNAs we isolated are identical with the cDNA pLK109 and the coding region of this gene. Other open reading frames are in close proximity to each of the 109 sequences. About 200 base-pairs 3' to the gene 1 109 sequence is an open reading frame in the opposite orientation. Gene 2 fragment contains a sequence that codes for a protein similar to trypanosome alpha-tubulin 728 base-pairs 5' to the 109 sequence. Gene 3 fragment possesses two additional putative coding regions, one 5' and another 3' to the 109 gene. There is a remarkable similarity between the 5' upstream regions of all three genes. Each possesses a normal Dictyostelium TATA box and the usual T stretch. In addition, there are many other portions of about 400 to 500 base pairs of the 5' regions that are either identical for long stretches or very similar. PMID- 2926810 TI - Nucleotide sequences of immunoglobulin-epsilon pseudogenes in man and apes and their phylogenetic relationships. AB - To understand the phylogenetic relationships between hominoids, the nucleotide sequences of immunoglobulin-epsilon processed pseudogenes from chimpanzee, gorilla and orangutan were determined. The basic structures of these processed pseudogenes agreed with their human counterpart. Although the degrees of nucleotide differences between man and the African apes had no statistical significance, all the analytical data examined supported the theory that chimpanzee is the closest relative of man. This result was consistent with that deduced by our recent qualitative study. Studies on the nucleotide sequences of globin genes have suggested that the molecular clock runs more slowly in hominoids than in non-hominoid primates. According to the present data, however, further retardation of the evolutionary rate was not observed in the human lineage. Assuming that orangutan diverged 14 million years ago and that the evolutionary rate between the orangutan lineage and the lineage leading to the other three species is constant, the divergence dates of chimpanzee and gorilla were estimated to be 4.9(+/- 0.9) and 5.9(+/- 0.9) million years ago, respectively. PMID- 2926811 TI - Hyperreactivity of B-Z junctions to 4,5',8-trimethylpsoralen photobinding assayed by an exonuclease III/photoreversal mapping procedure. AB - We have developed an exonuclease III/photoreversal procedure to map, with base pair resolution, the bases that have photoreacted with 4,5',8-trimethylpsoralen (Me3-psoralen) forming either monoadducts or interstrand crosslinks in DNA. This assay allows quantification of relative rates of Me3-psoralen photobinding to bases in DNA at levels less than one crosslink per 8000 base-pairs. We demonstrate the applicability of the Me3-psoralen mapping procedure on the Z forming sequence GAATT(CG)6-TA(CG)6AATTC. The results confirm our previous findings that Me3-psoralen forms crosslinks in the 5'TA within the (CG)6TA(CG)6 sequence when it exists in the B conformation but not when it exists in the Z conformation. In addition, with increasing superhelical density we observe at least a hundred-fold increased Me3-psoralen presumably represent B-Z junctions. The two presumed junctions respond differently with increasing negative superhelical tension, however, suggesting that the structures of these negative superhelical tension, however, suggesting that the structures of these junctions differ. This increased Me3-psoralen photoreactivity provides a positive signal for the presence of Z-DNA. The sequence and assay described here provide a "torsionally tuned probe" for determining the effective superhelical density of DNA in vivo. PMID- 2926812 TI - Functional organization of the plasmid pT181 replication origin. AB - Replication of the staphylococcal plasmid pT181 is initiated at the origin (ori) with the introduction of a site-specific nick by the plasmid-encoded initiator protein RepC. Deletion analysis showed that a sequence of about 70 base-pairs is required for full ori function, including the ability to compete with a co resident wild-type origin for the trans-acting RepC protein. A shorter sequence of 43 base-pairs is sufficient for origin function in the absence of competition. Single and double point mutations within these 43 base-pairs were used to determine the sequence requirement for replication within the minimal origin. Deletion mutants and point mutants were tested in replication and competition assays in vivo and in vitro, and in a RepC-mediated nicking assay. PMID- 2926814 TI - Cloning and deletion mutagenesis using direct protein-protein interaction on an expression vector. Identification of the calmodulin binding domain of alpha fodrin. AB - We have screened a lambda gt11 library, constructed with mouse macrophage cDNA, in order to isolate clones that code for calmodulin binding proteins. We have developed a new approach for this purpose using radioactive calmodulin (produced by genetic engineering) to detect fusion proteins that interact with this protein with high affinity. A cDNA clone that codes for mouse macrophage fodrin was isolated, sequenced and identified. By deleting part of the sequence the calmodulin binding domain was located on the fodrin sequence. The site is situated on repeat 11 of fodrin and probably on the extra arm of this repeat. The method we developed is widely applicable to site-directed mutagenesis of interacting proteins. PMID- 2926815 TI - Image reconstruction of the flagellar basal body of Caulobacter crescentus. AB - The bacterium Caulobacter crescentus has a single polar flagellum, which is present for only a portion of its cell cycle. The flagellum is ejected from the swarmer cell and then synthesized de novo later in the cell cycle. The flagellum is composed of a transmembrane basal body, a hook and a filament. Single-particle averaging and image reconstruction methods were applied to the electron micrographs of negatively stained basal bodies from C. crescentus. These basal bodies have five rings threaded on a rod. The L and P rings are connected by a bridge of material at their outer radii. The E ring is a thin, flat disk. The S ring has a triangular cross section, the sides of the triangle abutting the E ring, the rod and the M ring. The M ring, which is at the inner membrane of the cell, has a different structure depending on the method of preparation. With one method, the M ring makes a snug contact with the S ring and is often capped by an axial button, a new component apparently distinct from the M ring. With the other method, the M ring is similar to that of S. typhimurium; that is, it contacts the S ring only at an outer radius and lacks the button. Averages of the rod-hook filament subassembly ejected by swarmer cells reveal that the rod consists of two parts with the E ring marking the approximate position of the break. The structures of basal bodies from two mutants defective in the hook assembly were found to be indistinguishable from wild-type basal bodies, suggesting that the assembly of the basal body is independent of the hook or filament assembly. PMID- 2926816 TI - Aplysia limacina myoglobin. Crystallographic analysis at 1.6 A resolution. AB - The crystal structure of the ferric form of myoglobin from the mollusc Aplysia limacina has been refined at 1.6 A resolution, by restrained crystallographic refinement methods. The crystallographic R-factor is 0.19. The tertiary structure of the molecule conforms to the common globin fold, consisting of eight alpha helices. The N-terminal helix A and helix G deviate significantly from linearity. The distal residue is recognized as Val63 (E7), which, however, does not contact the heme directly. Moreover the sixth (distal) co-ordination position of heme iron is not occupied by a water molecule at neutrality, i.e. below the acid alkaline transition point of A. limacina myoglobin. The heme group sits in its crevice in the conventional orientation and no signs of heme isomerism are evident. The iron atom is 0.26 A out of the porphyrin plane, with a mean Fe-N (porphyrin) distance of 2.01 A. The co-ordination bond to the proximal histidine has a length of 2.05 A, and forms an angle of 4 degrees with the heme normal. A plane containing the imidazole ring of the proximal His intersects the heme at an angle of 29 degrees with the (porphyrin) 4N-2N direction. Inspection of the structure of pH 9.0 indicates that a hydroxyl ion is bound to the Fe sixth co ordination position. PMID- 2926813 TI - Nuclear factor I can functionally replace transcription factor Sp1 in a U2 small nuclear RNA gene enhancer. AB - Polymerase II transcription of a human gene for the small nuclear RNA U2 is dependent on two different promoter elements: a TATA-equivalent proximal sequence element and a distal enhancer element, which has been shown to contain Sp1- and octamer-binding sites. We have investigated the functional interplay between these transcription factor-binding sites of the enhancer, following transfection of U2 maxigene constructions into HeLa cells. There is a functional non-additive co-operation between the octamer-binding factor and Sp1, which is not dependent on the evolutionally conserved steric arrangement of these binding sites. We demonstrate that the conserved Sp1-binding site of the U2 enhancer can be fully substituted by a nuclear factor I (NFI) binding site, and that the octamer binding factor functions in stimulating transcription in conjunction with either Sp1 or NFI. Since the octamer-binding factor is most probably the same protein as nuclear factor III (NFIII), the results imply that the NFI/NFIII complex, involved in adenovirus DNA replication, also can function as an efficient activator of transcription. PMID- 2926817 TI - Refinement of the 7 Fe ferredoxin from Azotobacter vinelandii at 1.9 A resolution. AB - The recently redetermined structure of the 7 Fe ferredoxin from Azotobacter vinelandii has been refined against a new 1.9 A data set. The crystallographic R factor is 0.215 for all 9586 observed reflections 8.0 to 1.9 A. The model contains 106 amino acid residues, two Fe-S clusters and 21 water molecules. The root-mean-square deviations from ideality of bonds and angles are 0.014 A and 3.3 degrees, respectively. The refinement confirms the presence of two free cysteines: the thiol of C11 is in association with the side-chain of K100; the thiol of C24 is 3.35 A from inorganic sulfur of the [4 Fe-4 S] cluster. The refinement confirms a [3 Fe-4 S] model for the 3 Fe cluster. The two Fe-S clusters have similar bond distances and angles. The structure of the protein for residues 1 to 57 superposes within 0.85 A on residues 1 to 53 of the 8 Fe ferredoxin structure for main-chain N, CA and C atoms, if residues 9, 10, 29 and 30 of 7 Fe ferredoxin are omitted. These residues are part of two loops in contact with residues of the extended C-terminal chain of 7 Fe ferredoxin. PMID- 2926818 TI - Crystal structure of muconolactone isomerase at 3.3 A resolution. AB - The crystal structure of muconolactone isomerase from Pseudomonas putida, a unique molecule with ten 96 amino acid subunits and 5-fold, and 2-fold symmetries, has been solved at 3.3 A resolution. The non-crystallographic symmetries were used to refine the initial single isomorphous replacement phases and produce an interpretable 10-fold averaged map. The backbone trace is complete and confirmed by the amino acid sequence fit. Each subunit is composed of a body with two alpha-helices and an antiparallel twisted beta-sheet of four strands, and an extended arm. The helices and the sheet fold to form a two-layered structure with an enclosed hydrophobic core and a partially formed putative active site pocket. The C-terminal arm of another subunit related by a local dyad symmetry extends over the core to complete this pocket. The decameric protein is almost spherical, with the helices forming the external coat. There is a large hydrophilic cavity in the center with open ends along the 5-fold axis. Molecular interactions between subunits are extensive. Each subunit contacts four neighbors and loses nearly 40% of its solvent contact area on oligomerization. PMID- 2926819 TI - Molecular mechanics model of supercoiled DNA. AB - We describe a pseudo-atomic model of supercoiled DNA. Each base-pair of the DNA is represented in the model by three particles placed in a plane. The particle triplets are stacked to model stacked base-pairs in double-helical DNA, and closed circular conformations are generated to investigate supercoiling. This model is less detailed than all-atom models, which are too computationally demanding to be used to study supercoiling. On the other hand, this model contains details at the base-pair level and is therefore more elaborate than elastomechanical models. A potential energy function is written in terms of a set of internal co-ordinates defined to resemble a limited number of helical parameters. The modeled helical parameters, helical twist, base-roll, tilt and rise, are the most important parameters of the global shape of DNA. Experimentally measured mechanical properties of DNA are used to define the forces holding the particles together. We then use a procedure incorporating energy minimization and molecular dynamics to locate low energy conformations of the model DNA. The model was found to behave very much like rubber-tubing and elastomechanical models. The conformations and the effects of supercoiling pressure (a number proportional to the degree to which the total twist of the DNA has been altered from its natural value) on these conformations are all very similar to those observed in the latter two models. We also used this model to examine the effects of supercoiling pressure, base-sequence and mechanical properties on the conformations and energies of five sequences. The sequences studied include models of naturally straight DNA and DNA with static or natural bends. PMID- 2926820 TI - Sequence analysis of the complete Caenorhabditis elegans myosin heavy chain gene family. AB - The sequences of three myosin heavy chain (MHC) genes from Caenorhabditis elegans, myo-1, 2 and 3, are presented. These genes, together with unc-54, comprise the entire nematode sacromeric MHC family. Comparison of nematode MHC sequences and sarcomeric, smooth and non-muscle MHCs from other organisms highlights conserved sequence features of the MHC rod believed to be important for thick filament assembly. These include: conservation of sequence differences between individual 28 amino acid repeats; invariant placements of large aromatic residues, such as tryptophan, in the rod sequences; conservation of "weak spots" in the hydrophobic seam; and conservation of non-uniform charge distributions along the length of the rod. The rod sequences of the body wall isoforms A and B are more closely related to each other than to the pharyngeal isoforms C and D, suggesting that structural constraints have been imposed by their location within the same thick filament. We have also identified the major transcriptional start site for gene unc-54. Surprisingly, there are no TATA or other known transcription factor elements immediately upstream from the unc-54 start site, or in the upstream regions of the other genes of the C. elegans MHC gene family. PMID- 2926821 TI - GrB deletion of the chorion locus of the silkmoth Bombyx mori. Localization of the left breakpoint and isolation of the deletion junction. AB - In the silkmoth Bombyx mori, choriogenesis occurs through the developmentally controlled deposition of several related classes of chorion proteins onto the oocyte by surrounding follicular cells. In the GrB mutant strain, a distinctive family of proteins (Hc) normally expressed late in choriogenesis, as well as several proteins of middle development specificity, are missing due to the deletion of the corresponding genes from the chorion locus. In addition, a smaller set of proteins normally confined to mid-choriogenesis is found to be prolonged in expression in homozygote mutant but not heterozygote individuals. To elucidate the molecular organization of the chorion locus in the GrB genotype, we scanned a part of the wild-type locus represented by a chromosomal walk of 270,000 bases through library screening and genomic DNA hybridizations using a series of unique probes. A chromosomal clone, GrB4, whose sequences showed the expected characteristics of the deletion junction, was isolated from a partial EcoRI library of mutant genomic DNA. Through comparative hybridizations, mapping and sequencing, the precise location of one of the deletion breakpoints was identified on one of the clones mapping in the characterized part of the wild type locus. Attempts to locate the other breakpoint in wild-type DNA and to extend the structural characterization past the deletion junction through chromosomal walking were unsuccessful, due to the apparent absence of these sequences from libraries of wild-type and mutant genomic DNA, respectively. Hybridizations of the deletion region on clone GrB4 to cDNA derived from follicular RNA indicate that no gene sequences are directly interrupted by the deletion, and reveal the presence of a gene sequence of unknown function 1000 to 5000 bases to the right of deletion junction. PMID- 2926822 TI - Phasing the meridional diffraction pattern of type I collagen using isomorphous derivatives. AB - The meridional X-ray diffraction pattern of wet rat tail tendon contains information about the one-dimensional structure, or axial projection of electron density distribution of the type I collagen fibril. Using synchrotron radiation we have determined the intensities of the first 50 meridional X-ray diffraction reflections. The approach of isomorphous addition with reagents, selected using criteria of chemical reactivity, which label at fewer sites than the stains used in previous studies was applied to phase these 50 reflections to produce a one dimensional electron density distribution map of a single D-repeat of the collagen fibril. This method is not model-dependent and thus constitutes the first unambiguous determination of the meridional phases of type I collagen. PMID- 2926823 TI - Molecular basis of eye lens transparency. Osmotic pressure and X-ray analysis of alpha-crystallin solutions. AB - Short range, liquid-like order of the crystallin proteins accounts for eye lens transparency. The relationship between structural and thermodynamic properties of eye lens was further investigated using osmotic pressure and small-angle X-ray scattering measurements of calf lens alpha-crystallins. The consistency of both data sets confirms that the macroscopic thermodynamic properties are determined by the structural properties accessible to X-ray scattering. In addition, the experimental data were correctly accounted for using a model developed in liquid state physics: the rescaled mean spherical approximation combined with a Verwey Overbeek potential. This model provides as best fit parameters the excluded volume, the charge and the diameter of an "equivalent" particle that compare well with the corresponding values found in the literature for alpha-crystallins. As a result, transparency may now be expressed as a function of a few structural parameters, the role of which is discussed. The approach presented here may be extended to studies of the thermodynamic-structural relationships of other protein solutions. PMID- 2926824 TI - A facile duplex-hairpin interconversion through a cruciform intermediate in a linear DNA fragment. AB - The duplex of d(GGTACGCGCGTGCGCGATGG) and d(CCATCGCGCGTGCGCGTACC) containing an inverted repeat has been studied by spectroscopic and electrophoretic techniques. Prior to melting this DNA fragment, like many other palindromes, transforms into hairpin structures but with four non-self-complementary bases ("dangling ends") at their termini. Most surprisingly, it is found that these dangling ends promote an unusually facile hairpin-duplex interconversion in contrast to very slow ones found in all the "blunt end" palindromes studied so far. Kinetic studies provide evidence, for the first time in a linear DNA fragment, that a cruciform intermediate is involved in the hairpin to duplex interconversion. PMID- 2926825 TI - Definitions and nomenclature of nucleic acid structure parameters. PMID- 2926826 TI - Growth of inhibitory innervation in a lobster muscle. AB - The fine structure of inhibitory innervation to a limb muscle was examined in larval, juvenile, and adult lobsters. The innervation is essentially similar in qualitative features among these different stages, although there are some marked quantitative changes associated with growth. From being localized to discrete regions in the larval muscle, the inhibitory innervation spreads to groups of muscle fibers in the early juvenile muscle and to single fibers in the late juvenile and adult muscles. Concurrently, its neuromuscular synapses enlarge in area, become perforated, and acquire more active sites of transmitter release. Inhibitory nerve terminals occur in close proximity to their excitatory counterparts in the muscles of larval and early juvenile stages, although in later stages this juxtaposition occurs preferentially in some muscle fibers but not others. The inhibitory innervation is, nevertheless, much more restricted in occurrence than is the excitatory innervation. PMID- 2926827 TI - Teratological study of malathion in the rabbit. AB - There has been much debate concerning the teratogenic potential of the organophosphate pesticides, including malathion, although few experimental studies have been performed on mammals. This study was designed to expand the range of animal species used in the testing of malathion and to further evaluate malathion's teratogenic potential. A 100-mg/kg dose regimen from d 7 to d 12 of gestation was administered to New Zealand white rabbits. This produced no detectable differences in the number of resorptions, fetal size, and external or visceral anomalies between the treated and control groups. This suggests, as has been previously reported, that malathion has little or no teratogenic potential in the mammal. PMID- 2926828 TI - Lack of a modifying effect by the diuretic drug furosemide on the development of neoplastic lesions in rat two-stage urinary bladder carcinogenesis. AB - The effect of the diuretic drug furosemide on two-stage urinary bladder carcinogenesis in F344 rats initiated by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was investigated with regard to possible promoting activity. BBN was administered at 2 doses, 0.01 or 0.05%, in drinking water for 4 wk, and thereafter furosemide was given by gavage 3 times weekly for 32 wk, 250 mg/kg body weight. Furosemide ingestion induced diuresis with an alkaline, hypotonic urine. No significant difference with regard to incidences of bladder lesions were apparent between furosemide and control groups. The present investigation indicated that neither furosemide nor its related polyuria acted as a promoter in two-stage urinary bladder carcinogenesis. PMID- 2926829 TI - Metabolism and nephrotoxicity of tetralin in male Fischer 344 rats. AB - Tetralin, a component of fuels, solvents, and varnishes, is metabolized in male Fischer 344 rats to 1-tetralol, 2-tetralol, 2-hydroxyl-1-tetralone, 4-hydroxyl-1 tetralone, 1,2-tetralindiol, and 1,4-tetralindiol. Rats treated with tetralin demonstrated the classic lesions of hydrocarbon-induced nephropathy. PMID- 2926830 TI - Inhibitory effect of benzene metabolites on nuclear DNA synthesis in bone marrow cells. AB - Effects of endogenously produced and exogenously added benzene metabolites on the nuclear DNA synthetic activity were investigated using a culture system of mouse bone marrow cells. Effects of the metabolites were evaluated by a 30-min incorporation of [3H]thymidine into DNA following a 30-min interaction with the cells in McCoy's 5a medium with 10% fetal calf serum. Phenol and muconic acid did not inhibit nuclear DNA synthesis. However, catechol, 1,2,4-benzenetriol, hydroquinone, and p-benzoquinone were able to inhibit 52, 64, 79, and 98% of the nuclear DNA synthetic activity, respectively, at 24 microM. In a cell-free DNA synthetic system, catechol and hydroquinone did not inhibit the incorporation of [3H]thymidine triphosphate into DNA up to 24 microM but 1,2,4-benzenetriol and p benzoquinone did. The effect of the latter two benzene metabolites was completely blocked in the presence of 1,4-dithiothreitol (1 mM) in the cell-free assay system. Furthermore, when DNA polymerase alpha, which requires a sulfhydryl (SH) group as an active site, was replaced by DNA polymerase I, which does not require an SH group for its catalytic activity, p-benzoquinone and 1,2,4-benzenetriol were unable to inhibit DNA synthesis. Thus, the data imply that p-benzoquinone and 1,2,4-benzenetriol inhibited DNA polymerase alpha, consequently resulting in inhibition of DNA synthesis in both cellular and cell-free DNA synthetic systems. The present study identifies catechol, hydroquinone, p-benzoquinone, and 1,2,4 benzenetriol as toxic benzene metabolites in bone marrow cells and also suggests that their inhibitory action on DNA synthesis is mediated by mechanism(s) other than that involving DNA damage as a primary cause. PMID- 2926831 TI - Lung retention and binding of [14C]-1-nitropyrene when inhaled by F344 rats as a pure aerosol or adsorbed to carbon black particles. AB - 1-Nitropyrene (NP), as found in the environment, is more typically associated with carbonaceous particles than found as an aerosol of the pure compound. To determine whether (and why) an association with particles resulted in prolonged lung retention of NP, rats were exposed to 14C-NP as a pure aerosol or adsorbed on carbon black particles. Total 14C retained in the lung was greater at all times from 0.5 h to 30 d after exposure to 14C-NP adsorbed to carbon black particles than after exposure to pure 14C-NP (p less than .05). The fraction of total 14C in lung bound to carbon black particles decreased steadily with time after exposure, indicating in vivo removal of NP from the particles. At 0.5 h after exposure, the fraction of the estimated deposited 14C that was covalently bound to lung macromolecules was twofold greater for NP adsorbed on carbon black than for pure NP. Covalently bound 14C in lungs increased with time after exposure to 14C-NP adsorbed to carbon black, reaching levels of approximately 1% of the deposited radioactivity at 7-30 d after exposure, whereas levels of covalently bound 14C declined with time after exposure to pure NP. Thus, at 30 d after exposure, the amount of 14C covalently bound to lung macromolecules was approximately 10-fold greater (p less than .05) in rats that inhaled 14C-NP adsorbed on carbon black particles than in rats that inhaled pure 14C-NP aerosols. These results suggest that association of NP with carbon black particles augments the interaction of reactive metabolites of NP with target macromolecules. This phenomenon is thought to be related to the slow release of NP from carbon black particles, and may augment the biological effects of inhaled NP when adsorbed on carbon black or similar particles in the environment. PMID- 2926832 TI - Combined nephrotoxicity of methylmercury, lead, and cadmium in Pekin ducks: metallothionein, metal interactions, and histopathology. AB - This report describes the metallothionein (MT) levels and accumulation of mercury, lead, and cadmium, as well as their interaction with tissue zinc, copper, and iron, and the histopathological changes in kidneys of ducks exposed to methylmercury chloride (MeHgCl), lead acetate (PbAc), and cadmium chloride (CdCl2), singly or in combination for 13 wk. Forty-eight female Pekin ducks, divided into 8 groups of 6 birds each, were fed diets containing no added metals (control), 8 mg MeHgCl/kg feed, 80 mg PbAc/kg feed, 80 mg CdCl2/kg feed, 8 mg MeHgCl + 80 mg PbAc/kg feed, 8 mg MeHgCl + 80 mg CdCL2/kg feed, 80 mg PbAc + 80 mg CdCl2/kg feed, and 8 mg MeHgCl + 80 mg PbAc + 80 mg CdCL2/kg feed. Cadmium (Cd) when administered alone or in combination caused a 60-fold increase in kidney MT levels, while methylmercury (MeHg) or lead (Pb) administration caused a threefold increase in kidney MT levels. No significant changes in kidney MT levels were observed when metals were administered concurrently when compared with single-treatment groups. Residue analysis revealed accumulation of administered metals in kidney tissue. However, lead administration resulted in accumulation of small amounts of this element in kidney tissue. Simultaneous administration of MeHgCl and PbAc significantly increased the accumulation of lead in kidney when compared with PbAc-treated group. Cadmium when administered alone or in combination caused an increase in the levels of zinc and copper in kidney. Administration of MeHgCl or PbAc either alone or in combination caused increased iron levels in kidney, while cadmium administration either alone or in combination caused decreased iron levels. Administration of cadmium either alone or in combination caused degenerative changes in kidney proximal tubules. The severity of degenerative lesions increased when cadmium was simultaneously administered with other metals. These results indicate that combined administration of MeHg, Pb, and Cd has no significant effect on kidney MT levels or on essential elements in kidney tissue when compared with single metal groups. However, there appears to be an increase in the severity of histopathologic changes. PMID- 2926833 TI - Soman toxicity during and after exposure to different environmental temperatures. AB - A systematic study has been conducted to determine physiological susceptibility to the potent anticholinesterase soman during and after exposure to different environmental temperatures. Rats were placed in an environmental chamber set at 1, 7, 15, 23, or 31 degrees C (80% relative humidity, RH) from 0000 to 0800 h. Soman injections were given subcutaneously (sc) at 0600 h (during thermal stress), or at 0810 h after removal from the chamber (injected and tested at 23 degrees C, 60% RH). The measures (taken 30 min after soman injection) included core temperature, grip strength, general state of health, and LD10 estimates (taken 2 h post injection). Soman exposure produced a dose-related effect on each measure under all thermal stress conditions. During thermal stress, soman exposure produced major changes in core temperature ranging from 26 to 41 degrees C, which were linearly related to the environmental temperature condition. After removal from the chamber, soman exposure reduced core temperature by only 1 degree C without regard to prior thermal stress temperature. Grip strength and subjective health rating were soman dose-related with only a minor chamber temperature influence. The toxicity of soman was increased during exposure to either cold or hot environments and after removal from the cold environments. The adrenal-cortical stress response to cold involves increased metabolism and oxygen requirement. The exception was the decreased toxicity observed when soman exposure occurred after removal from a hot environment, exacerbated by a failure in the respiratory system due to anticholinesterase exposure. The increased toxicity of soman while in or after removal from a cold environment is believed to be due to a generalized adrenal-cortical stress response. The increased soman toxicity while in a hot environment, but decreased toxicity after removal from the hot environment, provides an interesting subject for further research. PMID- 2926834 TI - Cytotoxic effects of benzene on mouse germ cells determined by flow cytometry. AB - Flow cytometric (FCM) DNA content measurements were performed on testicular monocellular suspensions obtained from mice exposed per os to 0, 1, 2, 4, 6, and 7 ml/kg body weight of benzene in order to investigate its cytotoxic action on germ cells. The effects of benzene were measured 7, 14, 21, 28, and 70 d after treatment. Benzene had no effect on testis weight, but FCM analysis showed the relative percentages of some cell subpopulations (tetraploid and haploid cells) to be different from the control pattern, indicating the occurrence of some cytotoxic damage to differentiating spermatogonia. These data demonstrate that spermatogenesis is sensitive to benzene single exposures as evidenced by an altered cell ratio of testicular cell types. PMID- 2926835 TI - Effects of soil on percutaneous absorption of toluene in male rats. AB - Previous assessments of health risks from soil-adsorbed chemical exposures relied on extrapolations from data derived with pure compounds. However, interactions between chemical and soil can alter the rate, amount, and form of chemical that enters the body, resulting in effects that are different from those that occur after exposures to chemical alone. In this study, male rats were treated dermally with [14C]toluene alone or adsorbed to either a sandy or a clay soil. Both soils produced a higher plasma concentration compared to pure toluene, with a statistical decrease in half-life of absorption observed after sandy soil adsorbed treatment. The time to reach peak plasma concentration, half-life of elimination, and area under the plasma concentration-time curve (AUC) were similar for all groups. Skin and fat contained the highest concentration of radioactivity 48 h after all treatments. Pure and soil-adsorbed toluene were primarily metabolized and excreted via the kidney rather than exhaled. Furthermore, soil treatment did not alter the percentages of the metabolic products. PMID- 2926836 TI - Identification and cDNA cloning of a new member of the L2/HNK-1 family of neural surface glycoproteins. AB - Rabbit antibodies raised against a 135- to 140-kD glycoprotein isolated from the culture medium of mouse forebrain explants were used for the identification and cloning of a complex of mouse neural cell surface glycoproteins. The antibodies recognized a 135-kD surface protein which shared the L2/HNK-1 epitope with several neural cell adhesion molecules. Three homologous complementary deoxyribonucleic acid (cDNA) clones were isolated from a mouse brain cDNA library prepared in the expression vector lambda gt11, one of which was sequenced and found to lack sequence homologies with known proteins. In Northern blots, this clone hybridized with a single 6.3 kb messenger ribonucleic acid (mRNA). In immunoblots of mouse brain extracts, antibodies raised in rabbits against the fusion protein encoded by it stained two glycoproteins of 135 and 90 kD, which we designated F3.135 and F3.90. In the developing mouse cerebellum, F3 antigenic sites were found predominantly on parallel fibers and on postmitotic neurons. In fetal brain cell cultures, F3 antigen was detected at the surface of cells with neuronal morphology, but the antibodies also stained some non-neuronal cells in a pattern characteristic of matrix components. Because all proteins carrying the L2/HNK-1 epitope identified so far have a role in cell adhesion, it can be anticipated that the F3 surface proteins also are involved in cell-interaction phenomena. PMID- 2926837 TI - Identity of ED2-positive perivascular cells in rat brain. AB - A controversial, though fundamental, issue in neurobiology concerns the nature, origin, and function of brain macrophages. By immunocytochemical analysis using monoclonal antibodies directed against rat macrophage antigens, i.e., ED1-3, Ox 41, Ox-42, and Ki-M2R, we show that a group of perivascular cells located within the basal membrane of CNS blood vessels are immunoreactive. These cells, which resemble pericytes in terms of their anatomical distribution, are distinct from resting parenchymal microglia immunologically as well as morphologically. Our results demonstrate considerable heterogeneity in the immunophenotype of resident brain macrophages, which may be part of the immune-nervous system interface. PMID- 2926839 TI - A soluble brain molecule related to epidermal growth factor receptor is a mitogen inhibitor for astrocytes. AB - The astrocyte mitogenic activity of normal and injured rat brain extracts was greatly enhanced by antibodies to epidermal growth factor receptor (EGFR). The antibodies appear to act by removing from the extracts inhibitory molecules immunologically related to EGFR. Three molecular species recognized by anti-EGFR antibody in brain extracts (molecular weights 41, 52, and 69 kilodaltons) did not seem to originate from EGFR proteolysis. The increase in astrocyte mitogenic activity in brain tissue following injury correlated with a reduction in the levels of soluble EFGR-cross-reacting material and a decrease in mitogen inhibitory activity. The decrease in EGFR-related mitogen inhibitor also correlated with a large increase in astrocyte membrane EGFR immunoreactivity, and intracerebral injection of antibodies to EGFR caused the appearance at the injection site of numerous EGFR-positive reactive astrocytes. Invasion of brain tissue by EGF/EGFR-related blood components may be the signal that initiates astrocyte activation. EGFR-related immunoreactive molecules are also present in extracts of other tissues and may have a general role in the control of cell division. PMID- 2926838 TI - Role of protein kinase C in glial cell proliferation. AB - Phorbol 12-myristate 13-acetate (PMA) has been shown to stimulate DNA synthesis and cell proliferation in a population of glial cells isolated from newborn rat brain. The non-tumor promoter 4 alpha-phorbol 12,13-didecanoate (4 alpha-PDD), on the other hand, was without an effect. The cultures treated with PMA displayed an extensive process formation and an increase in cell content. The tumor promoter induced [3H]thymidine incorporation into acid-precipitable material was completely blocked by 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), a potent inhibitor of protein kinase C (PKC), thereby suggesting a role for PKC in the control of DNA synthesis in glial cells. Subcellular fractionation and in vitro assay of PKC activity revealed a translocation of the enzyme from cytosol to particulate fraction in PMA-treated cultures. PMID- 2926840 TI - Novel astrocytic protein in multiple sclerosis plaques. AB - Monoclonal antibody J1-31 (MAb J1-31, isotype IgG 2b) was raised against crude homogenate of brain tissue from a multiple sclerosis (MS) patient (autopsy sample; Malhotra et al.: Microbios Letters 26:151-157, 1984). In human brain, MAb J1-31 recognizes an intracellular protein antigen (J1-31 antigen), which bands at approximately 30,000 daltons under reducing conditions for sodium dodecyl sulfate gel electrophoresis (Singh et al.: Bioscience Reports 6:73-79, 1986). By immunofluorescence microscopy, MAb J1-31 stains those cells that are also stained by antiserum to glial fibrillary acidic protein (GFAP), namely astrocytes, retinal Muller cells, and tanycytes in the ependyma (Predy et al.: Bioscience Reports 7:491-502, 1987). In addition, MAb J1-31 stains ciliated ependymal cells that do not express GFAP. Using a model system for gliosis (laceration-type injury of rat spinal cord), we were able to show that astrocytes responding to central nervous system injury exhibit greatly enhanced staining for J1-31 antigen (Predy et al.: Journal of Neuroscience Research 19:397-404, 1988; Predy and Malhotra: Brain Research Bulletin in press, 1989). In this article, we demonstrate that immunofluorescence staining owing to MAb J1-31 is greatly enhanced in MS plaques, as compared to adjacent "apparently normal" white matter. (This is consistent with previous results as MS plaques characteristically show an astroglial response [reactive gliosis] leading to the formation of a glial scar [McKhann: Annual Review of Neuroscience 5:219-239, 1982].) In addition, we present further evidence that J1-31 antigen is distinct from GFAP, although these two proteins may be associated spatially with one another. PMID- 2926841 TI - Is part of the molecular basis of the perineurial barrier function the lack of endogenous carbohydrate-binding proteins? AB - The sugar part of cellular glycoconjugates and specific endogenous sugar receptors, i.e., lectins, can establish a system of biological recognition based on protein-carbohydrate interactions. An assortment of labelled (neo)glycoproteins, carrying different types of sugar moieties, is synthesized to localize respective sugar receptors. With these tools, the histochemical patterns of endogenous carbohydrate-binding receptors of the epi-, peri-, and endoneurium were analyzed in human sural and accessory nerves and in swine sciatic nerve. This approach is complementary to the application of plant lectins, focusing on endogenous carbohydrate-binding proteins (lectins). In contrast to the epi- and endoneurium, which bound certain types of carbohydrates, such endogenous sugar receptors were histochemically not detectable in the perineurial cells. Moreover, no histochemical reaction was present in the "connective tissue septa" localized in the endoneurium in which the endoneurial vessels were embedded. This common property supplies evidence that these septa are composed of perineurial cells. They may represent a barrier in addition to the capillary endothelium. Our observations suggest histogenetical differences between the cell populations of epi- and endoneurium vs. perineurium. This significant difference in the ability to bind carbohydrate residues, conjugated to a carrier protein, is contradictory to the assumption that perineurial cells and fibroblasts are functional variants of the same cell type. The histochemical patterns of endogenous carbohydrate binding receptors found in human and swine nerves were similar but not identical, with exception of the perineurium, reflecting phylogenetic differences in the expression of sugar-binding proteins. The absence of specific sugar receptors in perineurial cells, however, seems to be a more general phenomenon.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2926843 TI - Comparison of four severity scores in patients with head trauma. AB - This study examines the performance of four severity scores in a group of 70 consecutive patients with head trauma, hospitalized in the same neurosurgical ICU. On day of admission to the ICU, data were collected from each patient to compute Acute Physiology Score (APS), Simplified Acute Physiology Score (SAPS), Glasgow Coma Scale (GCS), and Therapeutic Intervention Scoring System (TISS). These four scores were statistically correlated with the outcome of patients. Results also indicate that GCS was superior to any other score in predicting outcome of patients and allowed better specificity and sensitivity. Regarding the level of care needed by patients, TISS was superior to any other scoring system. The difficulty in estimating individual prognosis is discussed, since scoring systems are aimed at classifying groups of patients, not individuals. It is concluded that GCS is a simpler and less time consuming method in predicting outcome of patients with head trauma. PMID- 2926842 TI - Basic fibroblast growth factor and nerve growth factor administered in gel foam rescue medial septal neurons after fimbria fornix transection. AB - Basic fibroblast growth factor (bFGF) recently has been established as a survival and transmitter-promoting neurotrophic agent for embryonic neurons in vitro. Its local application to lesioned adult optic and sciatic nerves has been shown to rescue axotomized retinal and sensory neurons that otherwise die. Following transection of the fimbria fornix pathway connecting the medial septum (MS) to the hippocampus, MS neurons undergo severe cell death, which can be prevented partially by infusion of nerve growth factor (NGF). In the same lesion paradigm, we find that 87% of these neurons visualized by cresyl-violet staining have disappeared by 4 weeks after unilateral fimbria fornix transection in adult rats. Implantation of gel foam soaked with 8 micrograms bFGF reduced neuron death to 68%. A similar rescue effect was seen with 0.3 microgram NGF. NGF administered at 20 micrograms reduced cell losses to 54%. Thus, bFGF rescued 22% and NGF at 20 micrograms 38% of the neurons that otherwise would have died. Choline acetyltransferase immunocytochemistry revealed dramatic losses of cholinergic neurons on the lesioned, compared with the unlesioned, side. Cholinergic neuron death was clearly reduced by the bFGF and NGF treatments. Basic FGF, in contrast to NGF, did not prevent a reduction in size of surviving neuronal cell bodies. Considered in the context of FGF being present in brain and hippocampal neurons, our results suggest a possible role for FGF as a neurotrophic factor for CNS neurons in vivo. PMID- 2926844 TI - Enhancing the safety of intraoperative RBC salvage. AB - Devices for intraoperative blood salvage remove plasma and, in theory, all of the cellular elements of blood except for rbcs. We have previously shown that complete white cell and platelet removal does not always occur and that the retained platelet-leukocyte deposit is potentially harmful (2). In this study we investigated the hydraulic conditions in the centrifuge bowl that allow activated platelets and leukocytes to adhere, the histology of the resulting cellular deposit, and the effects of reinfusing a saline extract of the deposit. Earlier work had suggested that the addition of calcium, of partially clotted blood, and of excessive saline should be avoided during intraoperative rbc salvage (2). The present observations explain, in part, why such measures would be expected to be beneficial. PMID- 2926845 TI - Use of the Clyburn External Fixator in fractures of the distal radius. AB - A study was organized to evaluate the use of a one-plane external fixation device to treat comminuted fractures of the distal radius. Clinical and roentgenographic data were obtained in 20 patients with a followup ranging from 12 to 20 months. The results were graded 14 excellent, 4 good, 2 fair, and none poor. The use of the Clyburn External Fixation Device with supplemental radial styloid Kirschner wire fixation achieved acceptable results in the treatment of comminuted distal radius fractures and proved to be easily applied. PMID- 2926846 TI - Cervical spine immobilization of penetrating neck wounds in a hostile environment. AB - Current guidelines concerning trauma suggest that cervical spine immobilization be performed on all patients with penetrating wounds of the neck. This study was undertaken to examine the risks and benefits likely to be found when such care is provided in a hazardous environment, such as the battlefield, or the scene of a terrorist attack or domestic criminal action. Data for casualties from the Vietnam conflict were reviewed to determine the potential benefit of cervical spine immobilization on the battlefield. In this population, penetrating cervical cord injury was always fatal and usually immediately so. Only 1.4% of all casualties who were candidates for immobilization might have benefitted from the care. However, the risk of performing immobilization in a hazardous environment is substantial since about 10% of casualties are incurred while helping other casualties. Mandatory immobilization of all casualties with penetrating neck wounds sustained in an environment hazardous to first aid providers has an unfavorable risk/benefit ratio. PMID- 2926847 TI - Analyses of the relationship between blood alcohol and nasal breath alcohol concentrations: implications for assessment of trauma cases. AB - To prevent serious complications and facilitate efficient and effective management of patients admitted to the emergency department or intensive care settings, it is extremely important to differentiate, quickly, between elevated concentrations of alcohol in the blood and compromised neurological status due to brain injury or other pathology. This research analyzed the relationship between blood alcohol concentrations (BACs) estimated from venous blood samples and those estimated from breath samples that were obtained using the Alco-Sensor III device with an attached tube for passive nasal breath sampling. Blood and breath samples, as well as brief medical histories and demographic and environmental data, were obtained and recorded for 35 adult trauma patients admitted to two major urban emergency departments. Passively expired nasal breath provided an excellent estimate of BAC measured from venous blood (range, 0 to 0.32) as evidenced in the extremely high regression coefficient (r = 0.99; slope = 1.22; p less than 0.0001). BAC assessment and monitoring, through the application of passive nasal breath sampling, provides a means of rapidly estimating BAC, and thus can facilitate diagnosis and the initiation of appropriate management and treatment. PMID- 2926848 TI - High-frequency percussive ventilation in patients with inhalation injury. AB - Inhalation injury complicated by bacterial pneumonia is now one of the primary causes of morbidity and mortality in patients with thermal injury. We have investigated the use of high-frequency percussive ventilation (HFPV) as a means of ventilatory support for these patients. We propose that high-frequency ventilation may decrease the incidence of pulmonary infection following inhalation injury and decrease the incidence of iatrogenic barotrauma caused by conventional ventilation. High-frequency ventilation was instituted initially as salvage therapy in a group of five patients. In each case, normocapnia or arterial pO2 saturation of greater than 90% on a FIO2 of 60% or less was achieved with high-frequency ventilation but not with conventional ventilation. A second group of ten patients was prospectively entered into a study on the use of HFPV in patients with inhalation injury. One patient was removed from the study, and one patient was unable to be ventilated because of severely noncompliant lungs. Eight patients with a mean age of 29 years and a mean burn size of 38% of the total body surface completed the protocol. All patients survived, two developed pneumonia, and one developed subcutaneous emphysema. These results suggest that HFPV is effective in the treatment of patients with severe inhalation injury. PMID- 2926849 TI - Serum antibody responses to pneumococcal vaccine after splenic autotransplantation. AB - Immunization with pneumococcal capsular polysaccharide vaccines is advocated after splenectomy; however, experimental and clinical data suggest an impaired antibody response in splenectomized individuals. This study examined the value of splenic autotransplantation at various sites in augmenting the antibody response to Type III pneumococcal capsular polysaccharide in mice immunized 3 months after operation. Splenectomy resulted in impaired antibody responses compared to sham operated mice (p less than 0.001) using an enzyme-linked immunosorbent assay. Mice with intraperitoneal splenic autotransplants, but not mice with subcutaneous or intramuscular transplants, had greater antibody responses compared to splenectomized mice (p less than 0.05). Antibody responses were elevated only in mice autotransplanted with 50% or more of the original splenic mass. Since autotransplantation of splenic tissue augments the antibody response to pneumococcal capsular polysaccharides, the combination of splenic autotransplantation and pneumococcal vaccination may confer more protection than either modality alone in individuals who must undergo splenectomy. PMID- 2926850 TI - Sternal fractures associated with spinal injury. AB - Twenty-eight cases of sternal fractures and/or dislocations were reviewed for the presence of associated spinal injury. Patient records and radiographs were studied. Sixteen cases had inadequate radiographs to rule out spine fracture. Three cases had known direct injuries to the sternum. Of the remaining nine patients, eight had spine fractures. All of the spine fractures were consistent with a flexion injury mechanism. Three patients had spine fractures at the thoracic level and four at the lumbar level. One patient had lower cervical and thoracic injuries. In the patients with spine injury, the proximal manubrial fragment tended to displace posteriorly. Similarly, the manubrium would move posteriorly in manubriosternal dislocations. A case of spontaneous sternal fracture in a patient with osteoporosis and multiple thoracic compression fractures is described. One patient had open reduction of the manubriosternal joint. Three patients who were admitted for their sternal injuries had spine fractures which were not recognized during the hospitalization. There were no cases of mediastinal injury in the patients with combined sternal and spinal injuries. Flexion injury to the spine may cause buckling of the sternum. However, indirect sternal injury continues to be overlooked. Careful evaluation for spine injuries should be done on all patients with sternal fractures and vice versa. PMID- 2926851 TI - Ureteral and renal pelvic injuries from external trauma: diagnosis and management. AB - To define the optimal methods of diagnosis and repair of ureteral and renal pelvic injuries, we reviewed the records of 18 patients with 19 collecting system injuries (16 penetrating, three blunt). Hematuria was absent in five of 16 patients. Intravenous urography was diagnostic of ureteral injury in three and normal or nondiagnostic in eight. Retrograde pyelography was performed in only one patient and was diagnostic of bilateral ureteral injury. Treatment consisted of primary repair (minimal or no debridement and closure) in 11 injuries, ureteroureterostomy (debridement and reanastomosis) in six, ureteroneocystostomy in one, and transureteroureterostomy in one. Ureteral stents were placed in 12 injuries, nephrostomy catheter in one, and both in two. Four patients had no form of diversion. Followup was available for 14 patients; serum creatinine values were normal in each. Results of imaging studies in 13 were normal in 11; one showed mild caliectasis and one a resolving urinoma. Both intravenous urography and initial urinalysis may be unreliable indicators of ureteral and renal pelvic injury, and high suspicion mandates exploration. Usually the urinary tract can be satisfactorily reconstructed. Satisfactory urinary diversion can be achieved in most cases with an internal ureteral stent. PMID- 2926852 TI - Operative treatment of acute hip fractures: its effect on serum creatine kinase, lactate dehydrogenase and their isoenzymes. AB - Serum creatine kinase, lactate dehydrogenase, and their isoenzymes were prospectively studied in 16 patients who underwent operative treatment of acute hip fractures. No perioperative myocardial infarctions occurred; however, two patients died of noncardiac causes. We found that skeletal muscle injury associated with operative treatment of acute hip fractures did not result in significant elevations of serum CK-MB or the LD-1/LD-2 ratio. CK-MB activity exceeding 5% of total CK activity was observed in five patients who did not experience acute perioperative myocardial infarction; however, no patient had an absolute CK-MB value exceeding 50 IU/L. Elevations of serum CK-MB exceeding 50 IU/L and a LD-1/LD-2 ratio exceeding 1.0, therefore, should not be attributed to skeletal muscle injury alone following the operative treatment of acute hip fractures. PMID- 2926853 TI - Gastric mucosal perfusion and injury: variation in the relationship over time. AB - Acute erosions of the gastric mucosa occur in a variety of clinical settings characterized by a mismatch between mucosal blood supply and demand. Using a canine model incorporating the clinically important insults, we examined the relationship between the gastric mucosal injury measured by planimetry and the animal's regional gastric perfusion measured before, during, and after hemorrhagic shock. The proximal gastric mucosa developed lesions which were inversely related to the amount of gastric flow through 2 hours of shock. In later shock and after reperfusion the relationship reversed, coinciding with the appearance of visible ulcerations. This work demonstrates that early in shock gastric blood flow is inversely related to mucosal injury, but late in shock and after reperfusion increased blood flow is associated with increased mucosal damage. PMID- 2926854 TI - Intraosseous crystalloid and blood infusion in a swine model. AB - The technique of intraosseous infusion has attracted increasing interest in recent years, and has proven valuable for drug administration. This study was undertaken to determine whether it was also a potential route for fluid resuscitation. Thirteen- or eighteen-gauge tibial intraosseous needles were placed in eight "large" (mean weight, 14.4 kg) and eight "small" (mean weight, 5.8 kg) swine and the flow rate of blood and saline measured under gravity and 300 mm Hg. Flow was significantly greater using 13-gauge needles in the "large" swine, significantly greater for saline than for blood, and for pressure infusion versus gravity in all animals. A fluid bolus of 20 ml/kg could be given to all animals in less than 10 minutes using pressure infusion. These data suggest that intraosseous infusion is a reasonable initial step in fluid resuscitation of pediatric subjects until more conventional vascular access has been established. PMID- 2926855 TI - Preservation of devitalized calvarium following high-voltage electrical injury: case reports. AB - Three victims of electrical injury with necrosis of a portion of the skull had excision of overlying necrotic soft tissue soon after injury with immediate coverage of the devitalized bone with soft-tissue flaps. In two instances, the flap was from adjacent scalp; in the other a free myocutaneous flap was used. All wounds healed without sequestration of bone. Necrosis of the calvarium was substantiated by evidence of nonperfusion on a radionucleotide bone scan. In each instance, a followup bone scan showed evidence of regeneration of bone. This experience supports an earlier observation which suggested that devitalized but intact calvarium following electrical injury does not need to be removed and is the perfect in situ bone graft. PMID- 2926856 TI - Ipsilateral traumatic supracondylar femoral and proximal tibial fractures following total knee replacement: a case report. AB - An unusual case with ipsilateral traumatic supracondylar femoral and proximal tibial fractures following total knee replacement is reported. Both fractures were complicated by delayed union. The fractures were successfully treated with custom-made, long-stemmed St. Georg hinged-knee prosthetic components. PMID- 2926857 TI - The vacuum arthrogram in the acutely injured knee: a case report. AB - Distraction of joints during radiography may produce a vacuum phenomenon. This is abolished by the presence of free fluid, and thus could be taken to indicate the absence of a serious acute injury. A case is presented of a vacuum arthrogram occurring in the presence of serious acute intra-articular trauma. PMID- 2926858 TI - Radiolucent foreign bodies in the hand: case report. AB - An unusual case of radiolucent foreign bodies (wood) in the hand is reported. Diagnosis rests on clinical suspicion and is often suggested by the injury mechanism. Management includes antibiotics, X-rays and in some instances CT scan before exploration in selected cases; re-exploration in this case 12 days after the initial operation revealed another large piece of wood, which was successfully removed. Split-skin grafting was done 10 days later, and the patient was asymptomatic with full range of motion 5 weeks after that. PMID- 2926859 TI - Palmar dislocation of the trapezoid: case report. AB - A case of palmar dislocation of the trapezoid, associated with radial subluxation of the trapezium, is presented. This rare injury was treated by internal fixation. A satisfactory clinical result is noted 4 years later. PMID- 2926860 TI - Intravenous fluid administration and uncontrolled hemorrhage. PMID- 2926861 TI - Manual test for differential diagnosis between weakness of the trapezius and serratus anterior muscles. PMID- 2926862 TI - Canadian Society of Otolaryngology-Head and Neck Surgery, 43rd annual meeting. April 30-May 3rd, 1989, Toronto. Abstracts. PMID- 2926863 TI - Characterization of Moloney murine leukemia virus mutants with single-amino-acid substitutions in the Cys-His box of the nucleocapsid protein. AB - To study the function of the retroviral nucleocapsid protein (NC), we have constructed point mutations in the gag gene of Moloney murine leukemia virus (MuLV) that affect a conserved cysteine-histidine motif of NC. The mutants were characterized biologically and biochemically. Cell lines producing the mutant virions were constructed in NIH 3T3 and rat2 cells, and the viral particles released by these cells were characterized for protein and RNA content. The results indicated that most mutations block replication and specifically inhibit the packaging of the MuLV genomic RNA. In some of the mutants, the packaging of the endogenous rat VL30 RNA was not affected as profoundly as was MuLV RNA. NC also seems to have another function distinct from dimer formation and packaging: one mutation reduced viral RNA packaging by only fivefold but completely abolished viral cDNA synthesis, suggesting a defect in reverse transcription. PMID- 2926864 TI - Resolution of vaccinia virus DNA concatemer junctions requires late-gene expression. AB - Vaccinia virus replicates in the cytoplasm of infected cells, generating transient replicative intermediates containing the DNA for the terminal sequences as concatemeric junctions. The processing of the terminal sequences for a series of vaccinia virus conditional lethal mutants at the nonpermissive temperature was analyzed by restriction enzyme digestion and Southern blot hybridization of DNA isolated from infected cells. Three phenotypes were observed: DNA replication negative (Rep-), DNA replication positive but concatemer resolution negative (Rep+ Res-), and DNA replication positive and concatemer resolution positive (Rep+ Res+). Interestingly, all six Rep+ Res- mutants from separate complementation groups were defective in late protein synthesis. Isatin beta thiosemicarbazone, a drug that blocks late protein synthesis, also prevented resolution of concatemers. Orthogonal field gel electrophoresis of the DNA generated by the late defective mutants revealed a distribution of linear genome multimers. The multimers were processed into mature monomers after a shift to the permissive temperature in the presence of cytosine arabinoside for all the Rep+ Res- mutants except ts22, an irreversible mutant which cleaves RNA late in infection (R.F. Pacha and R.C. Condit, J. Virol. 56:395-403, 1985). Genome formation can be divided into two stages: DNA replication, which generates concatemers, and resolution, which processes concatemers into monomers with hairpin termini. Early viral genes are required for the former, and late viral genes are required for the latter. PMID- 2926865 TI - Hepatitis delta virus (HDV) and woodchuck hepatitis virus (WHV) nucleic acids in tissues of HDV-infected chronic WHV carrier woodchucks. AB - The molecular forms of genomic and antigenomic hepatitis delta virus (HDV) RNA and of woodchuck hepatitis virus (WHV) DNA and WHV RNA were studied in nonneoplastic liver (NL) tissues, hepatocellular carcinoma (HCC) tissues, and several extrahepatic tissues of chronic WHV carrier woodchucks acutely (two animals) and chronically (six animals) superinfected with HDV. HDV was shown to replicate in all NL and HCC tissues but not in any of the extrahepatic tissues analyzed, which included spleen, peripheral blood lymphocytes, kidney, ovary, testis, thymus, lung, and stomach. HDV RNA was present as species with molecular weights consistent with those of monomers, dimers, and trimers of both strand polarities, supporting the rolling circle model proposed for HDV RNA replication. WHV DNA levels in NL, HCC, spleens, and serum were 10- to 100-fold lower than the levels typically observed in chronic WHV carrier woodchucks not infected with HDV. WHV DNA replicative intermediates were rarely observed and only at very low levels, representing less than 10% of the total WHV DNA. By contrast, WHV RNA transcription was not significantly depressed and both primary WHV RNA transcripts, 2.3 and 3.6 kilobases, were observed in NL, HCC, spleens, and in one of the kidney tissues. In addition, a 2.6-kilobase WHV RNA transcript was found in the majority of the NL tissues. PMID- 2926867 TI - Homologous interference of lymphocytic choriomeningitis virus involves a ribavirin-susceptible block in virus replication. AB - Depending on the multiplicity of infection (MOI), infection of L929 cells results in either productive lymphocytic choriomeningitis virus replication or homologous interference M. Bruns, A. Gessner, H. Lother, and F. Lehmann-Grube, Virology 166:133-139, 1988). As shown in this communication, productive lymphocytic choriomeningitis virus replication as observed at a low MOI was effectively inhibited by ribavirin. In contrast, virus yields increased if cells were infected with a high MOI and in the presence of 5 microM of the antiviral compound. This drug-dependent release of infectious virus was preceded by enhanced nucleoprotein (NP) synthesis, a change in intracellular NP distribution, and by an onset of glycoprotein synthesis. It is therefore proposed that this block in viral replication is brought about by a posttranslational effect on a viral gene product, probably the NP, present in reasonably large quantities both during homologous interference as well as persistent infection. PMID- 2926866 TI - Sindbis virus mutations which coordinately affect glycoprotein processing, penetration, and virulence in mice. AB - Rapid penetration of baby hamster kidney cells was used as a selective pressure for the isolation of pathogenesis mutants of the S.A.AR86 strain of Sindbis virus. Unlike most Sindbis virus strains, S.A.AR86 is virulent in adult as well as neonatal mice. Two classes of mutants were defined. One class was attenuated in adult mice inoculated intracerebrally as well as in neonatal mice inoculated either intracerebrally or subcutaneously. Sequence analysis of the glycoprotein genes of the parent virus and three such mutant strains revealed a single point mutation which resulted in an amino acid change at position 1 in the E2 glycoprotein. The change from a serine in S.A.AR86 to an asparagine in the mutants created a new site for N-linked glycosylation which appeared to be utilized. This mutation did not retard release of infectious particles; however, mutant virions contained the E2 precursor protein (PE2) rather than the E2 glycoprotein itself. The mutants also lost the ability to bind two E2-specific monoclonal antibodies, R6 and R13. A second class of mutants was attenuated in neonatal mice upon subcutaneous inoculation but remained virulent in adults and in neonates when inoculated intracerebrally. Sequence analysis of three such strains revealed the substitution of an arginine residue for a serine at position 114 in the E2 glycoprotein. Reactivity with monoclonal antibodies R6 and R13 was reduced, yet members of this mutant class were more susceptible than S.A.AR86 to neutralization by these antibodies. PMID- 2926869 TI - Investigative grammar. PMID- 2926868 TI - The effect of hyperthermia on human prostatic carcinoma cell lines: evaluation in vitro. AB - The effect of hyperthermia on established human prostate carcinoma cell lines (PC 3, DU-145) and related sublines (1-LN, 125-1L) was investigated in vitro. Cells were exposed to heat treatment at 43C or 37C for varying time intervals, (one hr or two hrs) and cell survival was evaluated by the colony formation assay and by measurement of cellular growth rate. While one hr exposure at 43C did show a mean inhibition of colony formation, ranging from 29 to 41%, a statistically significant increase in inhibition rate (p less than 0.001) was observed at two hr exposure, ranging from 57 to 92%. This study is a report of the cytotoxic effect of hyperthermia on established human prostatic tumor cell lines. These in vitro results indicate that hyperthermia may become a potentially useful form of adjunctive therapy for local control of prostatic cancer. However, the temperature and exposure time may have an important impact on cell kill when this new modality for cancer treatment is proposed for a clinical trial. PMID- 2926870 TI - Renal hypercalciuria and acidification defect in kidney stone patients. AB - Calcium metabolism and renal acidification ability were examined in renal stone patients. On a random diet 33 of 52 patients excreted more than 4 mg. per kg. body weight per day of urinary calcium and were entered into a second study on a 300 mg. calcium diet. Absorptive and renal hypercalciuria was differentiated by fasting urinary calcium (mg. per 100 ml. glomerular filtration). Every absorptive hypercalciuria patient tested and 5 renal hypercalciuria patients had a normal renal acidification ability, and the serum parathyroid hormone and urinary cyclic adenosine monophosphate levels were normal. By calcium restriction urinary calcium decreased more in absorptive hypercalciuria than in renal hypercalciuria (2.48 +/- 0.14 versus 3.34 +/- 0.27 mg. per kg. body weight per day, p less than 0.05). However, urinary calcium remained high in 76 per cent of the patients with absorptive hypercalciuria. Nine patients had a defect in renal tubular acidification and the calcium metabolism was similar to those with renal hypercalciuria. Present studies show that renal hypercalciuria and renal tubular acidification defect cannot be differentiated without an ammonium chloride test. PMID- 2926872 TI - Critical evaluation of treatment of staghorn calculi by percutaneous nephrolithotomy and extracorporeal shock wave lithotripsy. AB - The combined use of percutaneous nephrolithotomy and extracorporeal shock wave lithotripsy in patients with staghorn calculi has become an established treatment regimen. We evaluated the results of 90 staghorn calculi-bearing kidneys treated with such combination therapy after a mean follow-up of approximately 2 years. A total of 69 kidneys (76.7 per cent) became free of stones at some point after treatment. However, due to stone recurrence this number decreased to 55 kidneys (61.1 per cent) at the end of follow-up. Patients who had undergone a previous open operation on the stone-bearing kidney showed less favorable results than the over-all group. When our results were compared to reported data on open surgery or percutaneous nephrolithotomy alone even better results may have been obtained by such treatment modalities. However, our data indicate that percutaneous stone debulking combined with further destruction of residual stone fragments by shock wave lithotripsy certainly is less invasive than an open operation and provides an alternative to percutaneous treatment alone, which can yield comparable results. PMID- 2926871 TI - The spectrum of metabolic abnormalities in patients with cystine nephrolithiasis. AB - To elucidate the pathophysiology of mixed stone formation in cystinuria, 27 patients with documented cystine nephrolithiasis underwent an inpatient evaluation under a constant dietary regimen. All patients had homozygous cystinuria, since the daily urinary cystine excretion exceeded 250 mg. per gm. creatinine. Hypercalciuria was noted in 5 patients (18.5 per cent), 4 of whom had fasting hypercalciuria. Hyperuricosuria was found in 6 patients (22.2 per cent) and it was not caused by a consumption of a diet rich in animal proteins, since urinary pH was higher and urinary sulfate lower than in control subjects. Serum uric acid was slightly lower and uric acid clearance was higher in hyperuricosuric patients than in control subjects. Hypocitraturia was found in 12 patients (44.4 per cent) and it was associated with defective renal acidification in 4 of 5 patients in whom it was tested. Thus, hypercalciuria, hyperuricosuria and hypocitraturia frequently accompany cystinuria in patients with cystine nephrolithiasis. These conditions might be renal in origin, rather than a result of dietary or environmental aberrations. They may contribute to the formation of calcium and uric acid stones, which sometimes complicate cystine nephrolithiasis. PMID- 2926873 TI - Early vascular control for renal trauma: a critical review. AB - To determine the incidence of, indications for and sequelae of temporary vascular occlusion in the management of renal trauma the records of 90 patients with 92 renal injuries were reviewed. Patients who required temporary vascular occlusion were compared to patients with similar injuries who also required renal surgery but not vascular occlusion. Only 11 of 92 renal injuries (12 per cent) required temporary vascular occlusion for reconstruction and control of renal bleeding. Neither the type nor the extent of renal and associated injury was a significant predictor of the need for occlusion. Renal injuries associated with large or expanding retroperitoneal hematomas were more likely to require temporary vascular occlusion than injuries without such associated hematomas. Temporary vascular occlusion was not associated with an increase in postoperative azotemia or mortality. The procedure is safe and effective, and allows for confident inspection and reconstruction of the kidney in patients who otherwise would be at high risk for nephrectomy. PMID- 2926874 TI - Conservative surgery for renal cell carcinoma: a single-center experience with 100 patients. AB - From January 1956 to March 1987, 100 patients underwent a conservative (parenchyma-sparing) operation as curative treatment for renal cell carcinoma at our clinic. This series includes 56 patients with bilateral (28 synchronous and 28 asynchronous) and 44 with unilateral renal cell carcinoma; in the latter category the contralateral kidney was either absent or nonfunctioning (17 patients), functionally impaired (17), involved with a benign disease process (6) or normal (4). The pathological tumor stage was I in 75 patients, II in 9, III in 10 and IV in 6. A nephron-sparing operation was performed in situ in 86 patients and ex vivo in 14. Postoperatively, 93 patients experienced immediate function of the operated kidney, while 7 required dialysis (4 temporary and 3 permanent). The incidence of dialysis was greater after ex vivo than in situ surgery (p equals 0.0005). The mean postoperative serum creatinine level in 97 patients with renal function was 1.7 mg. per dl. (range 0.9 to 4.6 mg. per dl.). The over-all actuarial 5-year patient survival rate in this series is 67 per cent including death of any cause and 84 per cent including only deaths of renal cell carcinoma. Survival was improved in patients with stage I renal cell carcinoma (p less than 0.05). Survival also was improved in patients with unilateral renal cell carcinoma (p less than 0.05) and fewer patients in this category had recurrent disease postoperatively (p less than 0.0005). Nine patients (9 per cent) had local tumor recurrence postoperatively and 5 of these were rendered free of tumor by secondary surgical excision. Conservative surgery provides effective therapy for patients with localized renal cell carcinoma in whom preservation of renal function is a relevant clinical consideration. PMID- 2926875 TI - Laser treatment of ureteral tumors. AB - Ureteroscopic laser coagulation was performed in 20 patients. In 4 of these patients endoscopic treatment was judged to be incomplete and biopsy demonstrated a muscle invasive tumor in 3 and a poorly differentiated tumor in 1. Therefore, segmental resection or nephroureterectomy followed. In the other 16 patients laser treatment alone (8) or in conjunction with electroresection (8) eradicated the tumor successfully. All of these were stage Ta or T1 and grade 1 or 2 tumors. Three recurrences (after 12, 24 and 49 months) were detected within a medium observation period of 13.8 months and could be eradicated easily with the laser, since these tumors were small. A ureteral stricture developed at the treatment site once in the "laser only" group and 3 times in the group with laser treatment and electroresection. Endoscopic laser coagulation seems to be a promising treatment modality for selected small ureteral tumors. Electroresection has a high risk for development of a ureteral stricture. Regular retrograde ureteropyelography is mandatory for follow-up. PMID- 2926876 TI - Retroperitoneal air, extracorporeal shock wave lithotripsy and epidural anesthesia. AB - During a 13-month period, 1,344 patients underwent extracorporeal shock wave lithotripsy. Plain x-rays done routinely 24 hours after lithotripsy to assess stone fragmentation revealed evidence of retroperitoneal air in 6 patients. All 6 patients had epidural anesthesia induced by loss of resistance to air in a syringe to identify the epidural space. It was believed likely that this was the cause of the air and 2 types of distribution were identified: 1 showed tracking of air along spinal nerves and 1 along tissue planes. This hypothesis eventually was confirmed by 2 patients in whom the air was identified after epidural anesthesia but before extracorporeal shock wave lithotripsy. Retroperitoneal air is found in a small number of patients undergoing epidural anesthesia and extracorporeal shock wave lithotripsy, and physicians treating these patients in the early postoperative period should be aware of this possible radiological finding and appreciate its benign nature. PMID- 2926877 TI - Use of amitriptyline in the treatment of interstitial cystitis. AB - A total of 25 patients with interstitial cystitis who had failed standard therapy with hydrodistension of the bladder during anesthesia and intravesical dimethyl sulfoxide instillation underwent treatment with the tricyclic antidepressant amitriptyline. The initial dosage of 25 mg. before bed was increased gradually during a 3-week period to 75 mg. at bedtime. Of the patients 20 were able to tolerate the medication for a minimum of 3 weeks and could be evaluated for response. A significant improvement was noted in pain and daytime frequency. Of 9 patients 8 experienced relief of dyspareunia and 11 of 19 reported diminished urinary urgency. Eight patients have experienced virtual total remission of symptoms and have been on the drug for 4 to 28 months. It appears reasonable to consider the use of amitriptyline in patients with interstitial cystitis refractory to standard therapy. PMID- 2926878 TI - Neoadjuvant treatment of stages T2 to T4 bladder cancer with cis-platinum, cyclophosphamide and doxorubicin. AB - In an ongoing phase II study 17 patients with potentially operable transitional cell carcinoma of the bladder (stages T2 to T4, Nx, Mo) have been treated with intravenous cis-platinum (50 mg.per m.2), cyclophosphamide (400 mg.per m.2) and doxorubicin (40 mg.per m.2). They were to receive 3 treatments at 3-week intervals before cystectomy and 2 treatments at 3-week intervals commencing 5 weeks after cystectomy. Of 17 patients 14 (82 per cent) completed all 3 preoperative treatments but only 7 (41 per cent) continued on to complete the entire 5 treatments. In most cases incomplete therapy was due to patient refusal. Toxicity was low as measured by World Health Organization standards. Of the 17 patients 9 (53 per cent) exhibited objective tumor response (pathological downstaging or greater than 50 per cent reduction of tumor volume determined by either computerized tomography scan and/or endoscopic examination. When the determination was made by endoscopy the changes were dramatic and not borderline.) No patient demonstrated a pathological complete response. All 9 of the responders (100 per cent) remain clinically free of disease at a median follow-up of 19 months (range 4 to 30 months). The 8 nonresponders have done poorly with 5 dead of disease, 1 alive with pelvic recurrence and 2 free of disease at 4 and 12 months. These tumor response rates compare favorably with other cis-platinum-based combination regimens. The response to the chemotherapy appears to be an important prognostic indicator. Phase III trials must be conducted to determine whether this neoadjuvant chemotherapy regimen has a significant effect on long-term patient survival. PMID- 2926879 TI - Intravesical bacillus Calmette-Guerin therapy for in situ transitional cell carcinoma involving the prostatic urethra. AB - A total of 23 patients presenting with multifocal superficial bladder cancer and concomitant in situ transitional cell carcinoma of the prostatic urethra (mucosal in 19 and ductal in 4) underwent transurethral resection and intravesical bacillus Calmette-Guerin therapy. Median followup was 51.6 months (range 6 to 105 months). Of the 23 patients 13 (48 per cent) had a complete response with a median followup of 43.7 months without recurrence. Progression of some type (local, muscle invasion or metastasis) occurred in 10 patients (44 per cent); none occurred in the prostatic urethra. Median interval free of progression was 55.7 months; 7 of 10 patients required cystectomy for progression or refractory disease in the bladder (prostate negative for transitional cell carcinoma). A trial of complete transurethral resection plus intravesical bacillus Calmette Guerin is a viable alternative to immediate radical cystectomy for patients with mucosal and/or ductal involvement of the prostatic urethra with in situ transitional cell carcinoma. PMID- 2926880 TI - Standardized evaluation of erectile dysfunction in 95 consecutive patients. AB - We investigated 95 patients referred for erectile dysfunction by penile blood pressure measurement, the intracavernous papaverine test and Doppler investigation of the penile arteries. Furthermore, penile cutaneous perception threshold, bulbocavernosus reflex latency and somatosensory cortical evoked potentials of the pudendal nerve were measured. In selected cases cavernosometry, cavernosography and corpus cavernosum electromyography were performed. Doppler investigation of the cavernous arteries after papaverine injection was more reliable than penile blood pressure measurement in the diagnosis of arteriogenic erectile dysfunction. Decreased sensibility of the penis may be the sole factor responsible for inability to sustain an erection. Erectile dysfunction may be provoked by impaired function of the pudendal nerve. Penile cutaneous perception threshold measurement and corpus cavernosum electromyography are mandatory in the evaluation of neurogenic etiology. Cavernosometry and cavernosography are reliable methods in the determination of abnormal drainage from the corpus cavernosum. PMID- 2926881 TI - Pathological stage is higher in older men with clinical stage B1 adenocarcinoma of the prostate. AB - We examined the relationship between age and pathological stage in 444 consecutive patients who underwent pelvic lymphadenectomy and radical retropubic prostatectomy for clinically localized adenocarcinoma of the prostate. Pathological stage of cancer was determined postoperatively as organ-confined, capsular penetration (cancer through prostatic capsule), seminal vesicle involvement or lymph node metastases. Patient age ranged from 34 to 75 years. The majority of the patients had clinical stage B1 disease with induration confined to less than 1 lobe of the gland. In this group a statistically significant (p equals 0.001, chi-square test for trend) correlation between increased age and higher pathological stage was found. We also found that older men with clinical stage B1 disease had a statistically significant trend toward higher Gleason grade. An explanation for our findings might be the masking of prostatic induration by benign prostatic hypertrophy, clearly a disease of aging men. We suggest that increased age is a relative risk factor for advanced pathological findings in men with clinical stage B1 prostatic cancer. PMID- 2926882 TI - Anaerobic bacteria in suppurative genitourinary infections. AB - Bacterial growth was obtained from specimens of 55 male and 48 female patients with localized suppurative genitourinary tract infections. The 55 male patients had abscesses of the genitalia (15), scrotal cyst (3), penis (7), testis (6), prostate (3), kidney (4), perinephric area (2) and periurethral area (4), wounds of the scrotum (3) and penis (6), and infected hydrocele (2). The 48 female patients had abscesses of Bartholin's cyst (26), vulva (4), vagina (4), labial cyst (2), kidney (2), perinephric area (1), periurethral area (3) and bladder (2), and a labial wound (4). Anaerobic bacteria only were present in 34 specimens (33 per cent), aerobic bacteria only in 7 (7 per cent), and mixed aerobic and anaerobic flora in 62 (60 per cent). A total of 275 isolates (189 anaerobic and 86 aerobic) was recovered, for an average of 2.6 isolates per specimen (1.8 anaerobes and 0.8 aerobes). The predominant anaerobes recovered were Bacteroides species (103 isolates) and anaerobic cocci (54). The most frequently recovered aerobes were Escherichia coli (26 isolates), Staphylococcus aureus (10) and Proteus species (8). These data illustrate that most suppurative genitourinary infections involve anaerobic bacteria. These findings have important implications regarding the culturing techniques of these infections and for the selection of antimicrobials for their management. PMID- 2926883 TI - Internal urethrotomy using a ureteral resectoscope. AB - A rigid 12F ureteral resectoscope is useful for internal urethrotomy of severe strictures over a conventional urethrotome. PMID- 2926884 TI - Simple aid for upright voiding after partial penectomy. AB - Inadequate penile length after partial penectomy may result in the socially unacceptable inability to project the urinary stream over the scrotum. A simple adaptation of a 60 cc syringe is described as an aid to contain and direct the urinary stream. PMID- 2926885 TI - Lower pole ureteropelvic junction obstruction and incomplete renal duplication. AB - The rare finding of lower pole ureteropelvic junction obstruction and incomplete renal duplication is discussed in 5 children. The children were divided into 2 groups, with short (less than 0.5 cm.) and long (greater than 4 cm.) lower ureteral segments. Short ureteral segment obstruction was managed by total excision of the narrow ureteral segment and end-to-side pyeloureterostomy. Obstructions associated with long lower ureteral segments were treated by excising the ureteropelvic junction and performing a standard Anderson-Hynes pyeloplasty. A thorough preoperative evaluation is helpful for successful management. PMID- 2926886 TI - Covered exstrophy and visceral sequestration in a male newborn: case report. AB - We report a case of a male newborn with complete epispadias and an umbilical lesion. Histological examination of the surgically removed lesion revealed a colonic remnant with no communication to the underlying bowel. This entity is one of the exstrophy/epispadias complex variants known as covered exstrophy with sequestered bowel, and is case 4 in the world literature. Simple excision of the lesion was accomplished with staged correction of the epispadias planned. PMID- 2926887 TI - Pelvic neuroblastoma. AB - Neuroblastoma usually presents as an upper abdominal mass arising from the adrenal gland. Recent experience with neuroblastoma of the spermatic cord, bladder and pelvis demonstrates the propensity of this tumor to arise in unusual areas. The need for unusual and unexpected masses in children to be evaluated thoroughly for neuroblastoma and for therapy to be individualized based on histological criteria, patient age and location of the tumor is demonstrated. PMID- 2926888 TI - Urological manifestations of the popliteal pterygium syndrome. AB - We report a case of the popliteal pterygium syndrome resulting in abnormalities of the external genitalia and testicular ectopia. Management included bilateral orchiopexy and complex genitoplasty. Pterygia represent errors in development that manifest as webs across joints and can result in anomalies of the external genitalia. The genitourinary aspects of the popliteal pterygium syndrome and their management are discussed. PMID- 2926889 TI - Percutaneous sclerotherapy of idiopathic varicocele in childhood: a preliminary report. AB - Of 31 boys 10 to 16 years old referred for treatment of a left grade II or III varicocele 28 underwent percutaneous sclerotherapy. Due to anatomical and technical obstacles sclerotherapy was not possible in 3 boys. At follow-up 1 of 16 boys (6.2 per cent) had a mild recurrence detected by Doppler sonography of the spermatic cord. Percutaneous sclerotherapy had no serious side effects, and proved to be an efficient and convenient treatment of left varicocele in childhood. PMID- 2926890 TI - Urinary volume in children with urolithiasis. AB - Urinary volume in 24-hour urine collections was examined in 50 children with hypercalciuria and urolithiasis or hematuria, 12 with idiopathic calcium oxalate urolithiasis and 36 healthy children. Urinary volume was 22.2 +/- 2.0 ml. per kg. per day in healthy children and 25.4 +/- 2.0 ml. per kg. per day in children with hypercalciuria, and it was similar in children with absorptive and renal hypercalciuria, and significantly lower in children with idiopathic calcium oxalate urolithiasis (12.2 +/- 1.4 ml. per kg. per day, p less than 0.001 from controls and children with hypercalciuria). Volume was not statistically different in hypercalciuric children with and without urolithiasis. Urinary sodium excretion in children with idiopathic calculi was not statistically different from controls. Urine osmolality was similar among the groups. Urinary volume represents a risk factor in children with idiopathic calcium oxalate urolithiasis, and increased fluid intake should be emphasized in such patients. PMID- 2926891 TI - Management of acute hydronephrosis of pregnancy by ureteral stenting: risk of stone formation. AB - Acute hydronephrosis of pregnancy has long been managed with ureteral stenting. Although many articles have been published recently concerning stent incrustation none has addressed the etiology. We report a case of accelerated incrustation due to the hypercalciuric state of pregnancy. We propose conservative management with hydration, calcium restriction and close monitoring for infections and stone debris. Antibiotic suppression and stent changes should not be used routinely but rather they should be individualized. PMID- 2926892 TI - Bizarre leiomyoma of the renal pelvis with ultrastructural and immunohistochemical findings. AB - Leiomyomas of the renal pelvis are rare tumors. To date only 4 cases have been reported. We present a unique case with cellular atypia in which ultrastructural and immunohistochemical findings are described. PMID- 2926893 TI - Renal angiomyolipoma associated with lymph node involvement and renal cell carcinoma in patients with tuberous sclerosis. AB - Renal angiomyolipomas are found in more than half of the patients with tuberous sclerosis. We report on 3 patients with tuberous sclerosis and pathologically aggressive renal angiomyolipoma with retroperitoneal lymph node involvement and/or renal cell carcinoma. All patients have had a benign course. The literature is reviewed and supports the benign nature of this seemingly aggressive disorder. An approach to the evaluation and treatment of a child with tuberous sclerosis and renal angiomyolipoma is presented. PMID- 2926894 TI - Hydralazine, hydrochlorothiazide and ampicillin associated with retroperitoneal fibrosis: case report. AB - A case of retroperitoneal fibrosis possibly associated with hydralazine, hydrochlorothiazide and ampicillin therapy is reported. PMID- 2926895 TI - Placenta percreta invading the bladder: report of 2 cases. AB - We report 2 cases of placenta percreta with invasion of the bladder that resulted in massive hemorrhage at cesarean section. Control was achieved by hysterectomy, bilateral internal iliac artery ligation, suture ligation of bleeding vessels and bladder repair, with no fetal or maternal mortality. PMID- 2926897 TI - Congenital glanular sinus: possible variant of blind accessory urethral channel. AB - We report a case of congenital sinus opening at an unusual position on the glans penis of an asymptomatic subject. The differential diagnosis and embryological implications of this rare anomaly are discussed. We believe that our case represents an uncommon location for a blind accessory urethral channel. PMID- 2926896 TI - Ectopic prostate tissue at the bladder dome. AB - A 71-year-old white man with asymptomatic microscopic hematuria had a sessile tumor at the dome of the bladder containing benign prostatic glandular tissue. Benign prostatic polyps occur commonly in the prostatic urethra and bladder neck as vestigial remains of embryonic prostatic elements. Ectopic prostatic tissue elsewhere is rare and has not been described previously arising at the bladder dome. The origin of prostate glands in this unlikely location is unclear. The clinical course of ectopic prostatic polyps at any location is benign, although local recurrence has been reported. PMID- 2926898 TI - Abscess of corpus cavernosum. AB - A rare case of abscess of the corpus cavernosum is described. The patient was treated successfully by surgical drainage and antibiotic therapy. A right penile deviation and a relatively poor erection were reported by the patient 6 weeks postoperatively but he did not require further surgery. The possible causes, diagnosis and treatment of this rare disease are discussed. PMID- 2926899 TI - Invasive giant condylomata acuminata: a case report. AB - We report on a patient with invasive giant condylomata acuminata (Buschke Loewenstein tumor). This tumor is an exophytic human papilloma viral lesion with downward growth without histological malignancy. The aggressive progression of this lesion requires early surgical excision with clear margins. Delay in recognition of this tumor can otherwise lead to a fatal clinical course. PMID- 2926900 TI - Large-cell calcifying Sertoli cell tumor. AB - We report on a 20-year-old man with a left testicular mass clinically believed to be a malignant neoplasm but subsequently identified as a large-cell calcifying Sertoli cell tumor. This is a rare form of Sertoli cell tumor with unique clinical and pathological features only recently described in the literature. The neoplasm has a low malignant potential with only 1 patient known to have had metastasis. The tumor occurs primarily during the first 2 decades of life and has been associated with endocrine disorders and cardiac myxoma. The clinician should be mindful of this tumor because of its low malignant potential and the necessity to evaluate individuals for endocrine and cardiac abnormalities. PMID- 2926901 TI - Primary leiomyosarcoma of the testis. AB - We report a case of primary leiomyosarcoma of the testis, which was believed to originate from normal testicular structures containing smooth muscle cells, such as blood vessels and contractile cells of the seminiferous tubules. No evidence of tumor spread was found. Treatment consisted of orchiectomy with high ligation of the spermatic cord. The patient received no adjuvant therapy. There was no evidence of tumor after 2 years. The literature is reviewed and the therapeutic approach is discussed. PMID- 2926902 TI - Fibromuscular hyperplasia of the seminal vesicle. AB - Examination of tissue removed during seminal vesiculectomy typically reveals few pathological abnormalities, although some tumors and cysts have been described. We report a case of seminal vesicle enlargement and pain due to fibromuscular hyperplasia. Complete pain relief ensued after seminal vesiculectomy. PMID- 2926904 TI - Re: Spontaneous subcapsular renal hematoma: diagnosis and management. PMID- 2926903 TI - Re: Percutaneous lithotripsy in morbid obesity. PMID- 2926905 TI - Re: Cavernosography in diagnosis of metastatic tumors of the penis: 5 new cases and a review of the literature. PMID- 2926906 TI - Scrotal cooling and testicular torsion. PMID- 2926907 TI - Re: Adjuvant radiotherapy after radical prostatectomy: is it indicated? PMID- 2926908 TI - This month in Investigative Urology: effects of shock waves on cells and tissues- critical factors in the conduct of research. PMID- 2926910 TI - The role of calcium antagonists in the management of renal warm ischemia. AB - Eighty dogs with solitary kidneys were used to investigate the effects of calcium antagonists on the functional capacity and structural integrity of kidneys subjected to sixty minutes of warm ischemia by transient vascular occlusion under general anesthesia. Treated dogs were compared with control animals who had normal or untreated ischemic kidneys (group 1 and 2) and also with saline-flushed ischemic kidneys without or with heparinization (group 3 and 4). Verapamil and nicardipine were used independently as local (group 5 and 7) or systemic treatment (group 6 and 8). Functional and structural studies revealed that calcium antagonists improved animal survival, renal hemodynamics, renal functional capacity, cellular adenine nucleotides, and reduced the ischemic structural damage. Local treatment of ischemic kidneys with 0.15 mg. nicardipine afforded the best protection against the deleterious effects of renal warm ischemia. PMID- 2926911 TI - Immunohistochemistry and cytochemistry of experimental rat bladder cancer: binding of the lectins PNA and WGA and of a Le(Y) mouse monoclonal antibody. AB - Two lectins, peanut agglutinin (PNA) and wheat germ agglutinin (WGA), and a mouse monoclonal antibody against blood group Le(Y) were used to study the distribution of carbohydrate antigens in an experimental rat bladder cancer model. Neoplasia was induced in 28 rats by intravesical installation of N-nitroso-N-methyl-urea (NMU). Fifteen rats were installed with the NMU solvent and served as controls. Urothelial samples were taken from all animals, the atypia were graded and detailed data on the location of the lectin-binding structures and the binding of the monoclonal antibody were obtained by immunohistochemical methods. Urine samples were collected at different times during tumor development and data on the cytological location of the lectin-binding structures and the binding of the monoclonal antibody were obtained by immunocytochemical methods. Examination of the histological distribution of lectin binding structures and Le(Y) antigen showed a characteristic change in carbohydrate antigen expression associated with the development of urothelial atypia. In normal urothelium carbohydrate antigens were present in cytoplasm, whereas they became expressed on cell membranes in non invasive carcinomas. Immunocytochemistry of urine specimens revealed a lack of correlation between the antigen expression found in exfoliated cells and that found in tissue. Morphologically normal cells from NMU-treated animals were found to express a carcinoma associated antigen pattern. PMID- 2926912 TI - The prevalence and distribution of proliferative and metaplastic changes in normal appearing canine bladders. AB - The prevalence and distribution of Brunn's nests, simple hyperplasia, simple squamous metaplasia, cystitis glandularis/cystica, atypical hyperplasia, and lymphocytic infiltration were studied by multiple histologic sections in 30 grossly normal urinary bladders obtained from a controlled population of dogs ranging in age from two to 14 years. The data were statistically analyzed using Fisher's exact test and logistic regression. A comparison of urothelial changes was made between dog and human. Brunn's nests were the most prevalent urothelial change and were observed at one or more locations in 80% of the cases. Simple hyperplasia was the second most common proliferative change and was observed at one or more locations in 66.7% of all cases. Brunn's nests (p less than 0.0001) and simple hyperplasia (p = .003) were significantly more likely to be found in the trigone. Simple squamous metaplasia was observed at one more more locations in 23.3% of all cases. Lymphocytic infiltration was observed in 20% of the animals; however, there was no statistically significant correlation between it and the urothelial changes. The trigone was by far the most common site (86.6% of all cases) for one or more lesions to be found. There was no evidence that inflammation was the cause of these urothelial changes. The data supports the concept that Brunn's nests, simple hyperplasia, and simple squamous metaplasia are normal variants of bladder urothelium in dogs and further that they are not precancerous changes. There was a similarity in prevalence, distribution, and significance of many urothelial changes between the dog and human which indicates that the dog is a good comparative model for studying diseases of the urinary bladder. PMID- 2926913 TI - Age-related differences in norepinephrine and non-collagenous protein in human vas deferens. AB - The existence of norepinephrine or non-collagenous protein in some tissues is believed to reflect the sympathetic discharge of the structures and plays an important role in contractile ability. Specimens of vas deferens were obtained from 44 subjects in various decades of life from age 20 to 84, and levels of norepinephrine, non-collagenous protein, collagen and elastin were determined. The level of norepinephrine and non-collagenous protein declined with increasing age. Both parameters inversely correlated with age. Collagen and elastin increased with advancing age. The regression line and coefficient of correlation between both variables showed significantly positive correlations. It is suggested that the contractile ability of human vas deferens, as defined by norepinephrine and non-collagenous protein contents, decreases with age, and the age-related increase in collagen and elastin may be of importance in reducing the contractile capability of this structure. PMID- 2926914 TI - AUA eighty-fourth annual meeting. American Urological Association, Inc. May 7-11, 1989, Dallas. Abstracts. PMID- 2926909 TI - Cytotoxicity of high energy shock waves: methodologic considerations. AB - In vivo and in vitro experimentation with high energy shock waves (HESW) is necessary to further our understanding of the biologic effects and potential application of this novel energy form. Factors are identified which are critical to the design and subsequent interpretation of HESW experimentation. First, the nature of the containment vessel and the presence or absence of acoustic interfaces are shown to significantly alter the outcome of cell suspension experiments. Second, the effects of HESW are shown to differ markedly for cells in suspension versus cells in tissue making comparisons between the two uncertain. Finally, the need for appropriate negative controls is demonstrated with in vivo experiments to control for the generalized toxicity which occurs when small animals are exposed to such an intense force distributed over a relatively large area. These findings affect the interpretation of previously reported work which investigated the cytotoxic potential of HESW. PMID- 2926915 TI - National Institute on Drug Abuse may join in anabolic steroid research. PMID- 2926916 TI - If youngsters overdose with anabolic steroids, what's the cost anatomically and otherwise? PMID- 2926917 TI - When it comes to child care, hospitals may be setting the pace for much of the nation. PMID- 2926918 TI - World Health Day emphasizes preventive efforts, teamwork to fight illness, injury, drugs. PMID- 2926919 TI - From the National Institutes of Health. PMID- 2926920 TI - Leads from the MMWR. Unintentional poisoning mortality--United States, 1980-1986. PMID- 2926921 TI - US and international standards for resuscitators. PMID- 2926922 TI - The exposure of health care workers to ribavirin aerosol. PMID- 2926923 TI - Intraperitoneal povidone-iodine. PMID- 2926924 TI - Chlorine, pH, and control of Legionella in hospital plumbing systems. PMID- 2926925 TI - Personal watercraft injuries. PMID- 2926926 TI - Outcomes of surgery in patients 90 years of age and older. AB - During the 11-year period 1975 through 1985, seven hundred ninety-five patients 90 years of age and older underwent operative procedures at the Mayo Clinic, Rochester, Minn. Overall serious morbidity within 48 hours after surgery was 9.4%, and the mortality was 1.6%. The 30-day, 1-year, and 5-year mortality rates were 8.4%, 31.4%, and 78.8%, respectively. Short-term morbidity and both short- and long-term mortality were highly associated with the American Society of Anesthesiologists physical status classification of the patient. Emergency procedures carried a significantly higher risk for morbidity and mortality within the 48-hour period and, to a lesser extent, for long-term mortality. Overall, poorer patient survival was associated with higher American Society of Anesthesiologists class; male sex; preoperative renal, liver, and central nervous system impairment; and surgery on the mouth, nose, or pharynx. When compared with age-, sex-, and calendar year--matched peers from the general population, there was a modest decrease in patient survival at 1 year that reversed by 2 years, with observed survival at 5 years comparable to the rate expected. PMID- 2926928 TI - Cyanocobalamin injections for patients without documented deficiency. Reasons for administration and patient responses to proposed discontinuation. AB - We reviewed the records of 1222 patients who attended a newly acquired rural satellite clinic and found that 120 (10%) had been receiving regular cyanocobalamin injections, but that only 4 (3%) met accepted criteria for its administration. Open-ended interviews with 48 of these patients revealed that they had been receiving cyanocobalamin injections for a mean of 9.9 years for 3.3 symptoms each and with a mean effectiveness rating of 2.9 (scale, 0 to 4). After receiving education regarding the appropriate indications for cyanocobalamin injections, 25 (52%) of the patients were willing to stop receiving them at least temporarily. However, 18 patients (38%) who were younger and who reported greater symptom relief would actively seek a physician who would continue to administer cyanocobalamin. Our findings suggest that some patients who have been receiving cyanocobalamin injections but who do not have a documented deficiency will stop receiving the injections when presented with reasonable alternatives. PMID- 2926930 TI - Providing medical services through school-based health programs. Council on Scientific Affairs. AB - Resolution 162, which was adopted at the 1987 Annual Meeting by the Board of Trustees, called on the American Medical Association to study the efficacy of school-based health clinics. Recent data show that a significant number of school aged youth are in need of an adequate source of health care. School-based health programs constitute a promising avenue for providing health services to adolescents, particularly in medically underserved areas. Although there are insufficient data to support universal establishment of school-based health programs, small-scale studies suggest that such programs are a viable means to increase access to health care for youth. PMID- 2926929 TI - Physician need. An alternative projection from a study of large, prepaid group practices. AB - To model a base level of physician demand in a managed health care system, we examined in 1983 the ratios by specialty of full-time equivalent physicians to health maintenance organization members in seven large, closed-panel health maintenance organizations, each with more than 100,000 members. The medical director of each plan was surveyed by mailed questionnaire and telephone interview to determine the plan's number of full-time equivalent physicians by specialty and members served. Out-of-plan physicians contracted by the group were included within the specialty distribution wherever possible. We compared our findings (4779.4 full-time equivalent physicians serving 4,297,790 members) with Graduate Medical Education National Advisory Committee and others' projections of physician need and supply. Based on this model and unknowns that might affect utilization, our study suggests that at least 111 physicians per 100,000 population would be necessary in a system that emphasized reduced utilization of services and that more primary care physicians would be needed than the Graduate Medical Education National Advisory Committee predicted would be available. PMID- 2926927 TI - Relationship of hearing impairment to dementia and cognitive dysfunction in older adults. AB - We conducted a case-control study in 100 cases who had Alzheimer's-type dementia and 100 age-, sex-, and education-matched, nondemented controls to evaluate the hypothesis that hearing impairment contributes to cognitive dysfunction in older adults. The prevalence of a hearing loss of 30 dB or greater was significantly higher in cases than in controls (odds ratio, 2.0; 95% confidence interval, 1.2 to 3.4), even when adjusted for potentially confounding variables. In addition, we observed a dose-response relationship in which greater hearing loss was associated with a higher adjusted relative odds of having dementia. Hearing loss was also significantly and independently correlated with the severity of cognitive dysfunction, as measured by the Mini-Mental State Examination, in nondemented as well as demented patients. These results demonstrate an association between hearing impairment and dementia and lend support to the hypothesis that hearing impairment contributes to cognitive dysfunction in older adults. PMID- 2926931 TI - Catheter-induced delayed recurrent pulmonary artery hemorrhage. Intervention with therapeutic embolism of the pulmonary artery. PMID- 2926932 TI - Analysis of flow-directed pulmonary artery catheterization. PMID- 2926933 TI - Enforcing informed consent requirements: form or substance? PMID- 2926934 TI - A piece of my mind. Native borne. PMID- 2926935 TI - Adolescent suicide. PMID- 2926936 TI - National Research Council adds its voice to campaign for a more healthy US diet. PMID- 2926937 TI - Leads from the MMWR. Results from the National Adolescent Student Health Survey. PMID- 2926938 TI - Leads from the MMWR. Trends in screening mammograms for women 50 years of age and older--Behavioral Risk Factor Surveillance System, 1987. PMID- 2926939 TI - Dressage for cardiologists: gallop or canter? PMID- 2926940 TI - Violent cardiology: rhythm reversion by patient inversion. PMID- 2926941 TI - Oral fluoroquinolone therapy for Clostridium difficile enterocolitis. PMID- 2926942 TI - Depression in medical students. PMID- 2926943 TI - Drugs in the institutionalized elderly. PMID- 2926944 TI - Postmenopausal estrogen use and heart disease risk factors in the 1980s. Rancho Bernardo, Calif, revisited. AB - Postmenopausal estrogen use and risk factors for heart disease were assessed in 1057 women, aged 50 to 79 years, who were enrolled in an ongoing study of residents of an upper-middle-class community. From 1984 through 1987, thirty-one percent of the women reported current estrogen use, a rate equivalent to that determined in one survey of the same population done from 1972 through 1974. Compared with nonusers, current users did not have a more favorable cardiac risk factor profile before use, but users were more likely to have had a surgically induced menopause and to have been estrogen users during the survey done from 1972 through 1974. Similar to our earlier findings, current estrogen use was associated with lower weight, diastolic blood pressure, and fasting plasma glucose level than nonuse. Levels of low-density lipoprotein cholesterol were inversely related to estrogen dose; levels of high-density lipoprotein cholesterol were positively related to the duration of use. In this cross sectional study, blood pressure and lipoprotein and plasma glucose levels were similar in women receiving estrogen alone and in women receiving combination estrogen and progestin therapy. PMID- 2926945 TI - A randomized trial to increase smoking intervention by physicians. Doctors Helping Smokers, Round I. AB - Sixty-six physicians were randomized to three groups to conduct a 1-month campaign to help their patients stop smoking. The workshop group received free patient education materials and a 6-hour training workshop. The materials group received free patient education materials, and the no-assistance group received nothing. A telephone interview was completed with 89% of the 6767 eligible adult patients seen during the month of the campaign. The brief training program and patient education materials marginally increased the smoking intervention activities of volunteer physicians in private practice. Both workshop and materials physicians asked 54% of their smoking patients to stop; no-assistance physicians asked 40%. One year later, 36% of patients who had not even been asked by their doctors if they smoked reported that they had tried to stop smoking. If the physician had asked the patient if he or she smoked, the probability of a quit attempt was 47%. Patients who had been asked if they smoked were more likely to claim to have stopped (13%) than patients who had not been asked (9%). However, the proportion of patients claiming continued abstinence (range, 12% to 14%) was not related to the group of the physician. PMID- 2926946 TI - Conflicts of interest in the management of silent ischemia. PMID- 2926947 TI - A piece of my mind. Mr Turner's toenails. PMID- 2926948 TI - Diagnostic and therapeutic technology assessment. Intrauterine devices. AB - The DATTA panelists emphasized the critical importance of patient selection when considering IUDs for contraception. The IUD is an acceptable method of contraception, especially for those women who are in the middle to older reproductive years, unable to take oral contraceptives, in a stable monogamous relationship, and not at risk for sexually transmitted diseases. Within these constraints, the panelists gave overwhelming support to the IUD as a safe and effective method of contraception. The minority opinion (two panelists) that these devices were not established for safety or effectiveness was based on concerns over possible infectious complications. PMID- 2926949 TI - Scientists seek to gain adherents, avert technological ignorance 'disaster'. PMID- 2926950 TI - Research increasingly focuses on possible genetic factors in complex problem of alcohol abuse. PMID- 2926951 TI - Guy's Hospital has seen changes in 163 years, now initiates 'model management' of its own. PMID- 2926952 TI - Proposed changes in Britain's health service stir varied reactions, widespread controversy. PMID- 2926953 TI - Fron the Alcohol, Drug Abuse and Mental Health Administration. PMID- 2926954 TI - Leads from the MMWR. Rubella and congenital rubella syndrome--United States, 1985 1988. PMID- 2926955 TI - Leads from the MMWR. Influenza vaccine composition recommendation for the 1989-90 season. PMID- 2926956 TI - Snoring: carve the snorer? Deafen the snoree? The Dutch cheese wax solution. PMID- 2926957 TI - Autopsies should be performed on all cases. PMID- 2926958 TI - Premarital HIV screening. PMID- 2926959 TI - HIV infection in 1968. PMID- 2926960 TI - Jewish law and the obligation of the physician to heal patients with AIDS. PMID- 2926961 TI - The treatment of obesity in adults. PMID- 2926963 TI - Food for thought. PMID- 2926962 TI - Dioxin levels in Vietnam veterans. PMID- 2926964 TI - Peroneal nerve palsy following sequential pneumatic compression. PMID- 2926965 TI - Bloody discharge from the nipple: the utility of cytology. PMID- 2926966 TI - Methadone maintenance programs in Sweden. PMID- 2926967 TI - Peanuts in infants: inhalants as well as allergens. PMID- 2926969 TI - An epidemiologic study of headache among adolescents and young adults. AB - Despite extensive description of headache among patients in specialty clinics and general practices in the United States, there have been few community-wide investigations. In a population-based telephone interview study of 10,169 Washington County, Maryland, residents who were 12 through 29 years old, 57.1% of males and 76.5% of females reported that their most recent headache occurred within the previous 4 weeks. Four or more headaches in the preceding month were reported by 6.1% of males and 14.0% of females. The average duration of the subjects' most recent headache was 5.9 hours for males and 8.2 hours for females; 7.9% and 13.9%, respectively, missed part of a day or more of school or work because of that headache. Within the month before interview, 3.0% of males and 7.4% of females had suffered from a migraine headache. Consultations with a physician, by specialty, for headache-related problems are described by sex and age of subjects, as is the use of specific prescription and nonprescription medications. PMID- 2926968 TI - 'Brain death' and organ retrieval. A cross-sectional survey of knowledge and concepts among health professionals. AB - A sample of 195 physicians and nurses likely to be involved in organ procurement for transplantation was interviewed about knowledge, personal concepts, and attitudes concerning "brain death" and organ donation. Only 68 respondents (35%) correctly identified the legal and medical criteria for determining death. Personal concepts of death varied widely. Most respondents (58%) did not use a coherent concept of death consistently; others (19%) had a concept of death that was logically consistent with changing the whole-brain standard to classify anencephalics and patients in a persistent vegetative state as dead. The findings demonstrate confusion about correct criteria for determining death and differences in concepts of death that might prove troublesome to the transplantation enterprise. We conclude that health professionals should do more to resolve the clinical and conceptual issues in the definition and determination of death before policies concerning organ retrieval are changed. PMID- 2926970 TI - Learning theories implicit in medical school lectures. PMID- 2926972 TI - A piece of my mind. Coping with fallibility. PMID- 2926971 TI - Appropriate confusion over 'brain death'. PMID- 2926973 TI - The heated dorsal hand vein: an alternative arterial sampling site. AB - Studies of substrate flux, isotope activity and metabolic balance frequently require arterial sampling. We evaluated: (1) whether substrate concentrations obtained from heated dorsal hand veins (HDHV) were comparable to samples obtained from the radial artery, (2) whether heat sufficient to arterialize HDHV altered contralateral forearm blood flow thus affecting flux calculations, (3) whether a +14 heating pad equaled a cumbersome +700 heating chamber, and (4) whether HDHV showed a dose-response curve to varying heat loads. In 12 normals, dorsal hand temperature was raised from 31.8 +/- 0.6 degrees C to 39.8 +/- 0.8 degrees C (chamber) and 39.3 +/- 0.3 degrees C (pad). Basal contralateral forearm blood flow (3.37 +/- 0.7 ml/100 ml tissue/min) was not significantly altered in the chamber (3.39 +/- 0.5 ml) or the pad (3.44 +/- 0.5 ml). Skin temperature of the unheated hand, an index of superficial blood flow (31.5 +/- 0.7 degrees C) did not change significantly in the chamber (31.6 +/- 0.7 degrees C) or the pad (31.2 +/- 0.7 degrees C). Forearm blood flow did not change with heating in eight postoperative patients. Comparative arterial and HDHV blood gases and 10 metabolic substrates from simultaneously drawn samples at various temperatures showed HDHV PO2 approached but did not equal arterial PO2 at temperatures greater than 39 degrees C. Glucose, amino acid, and substrate concentrations were comparable at 39 degrees C and did not change with increasing temperature. HDHV can reliably determine arterial substrate concentrations using an inexpensive heating pad. In cool environments (20-22 degrees C), contralateral forearm blood flow is not significantly altered. There is no benefit to heating the hand above 39 degrees C. PMID- 2926974 TI - Cord blood tryptophan concentrations and total cysteine concentrations. PMID- 2926975 TI - Energy expenditure during severe acute pancreatitis. AB - Energy expenditure (EE) was measured, during 3 consecutive days, in six patients suffering from acute pancreatitis. Measurements were achieved postoperatively, under mechanical ventilation, using a mass spectrometer system. EE represented 1.49 times (range: 1.08-1.78) the predicted resting energy expenditure (PREE) according to the reevaluated Harris-Benedict equation. There was a weak positive correlation between EE and core temperature and a negative correlation between EE and nitrogen balance. EE/PREE was not different between septic and nonseptic patients (1.58 +/- 0.06 vs. 1.39 +/- 0.07). The calculations of nutrient oxidation rate indicated a high protein catabolic rate, a neoglucogenesis, and a lipolysis. PMID- 2926976 TI - Hand grip dynamometry as a predictor of postoperative complications reappraisal using age standardized grip strengths. AB - A mechanical hand grip dynamometer was used to derive age- and sex-related standard grip strengths from 247 healthy volunteers between 16 and 95 yr old. Preoperative grip strength was measured in 90 patients and related to postoperative complication rates. A grip strength of 85% standard for age and sex was found to be the most effective cut-off for prediction of postoperative complications in terms of sensitivity and specificity, predicting 74% of the complications (p less than 0.05). Specificity is improved over previously published standards related to sex alone especially when assessing the elderly patient (50% vs 21%). A grip strength below the recommended cut-off for age and sex suggests that the patient is in a high-risk group and demands further investigation of nutritional status. Studies of pre-operative nutritional support for the at risk group need to be undertaken. PMID- 2926977 TI - Comparison of forearm muscle dynamometry with nutritional prognostic index, as a preoperative indicator in cancer patients. AB - We studied 95 patients with cancer of the gastrointestinal tract in various sites. The aim of the study was to compare the forearm dynamometry vs the prognostic nutritional index which was reported by Busby et al, 1890. We used these methods as preoperative prognostic indicators for postoperative mortality and morbidity. The forearm muscle dynamometry has greater positive predictive value (58.33 vs 32.4%), higher sensitivity (77.78 vs 66.6%), and specificity (86.11 vs 65.28%) than the prognostic nutritional index. The forearm muscle dynamometry predicted the patients mortality with a high rate of sensitivity (100%). The results suggest that dynamometry is a useful, rapid, and inexpensive test. It is more accurate than the nutritional index, and can identify cancer patients at a high risk of developing major postoperative complications, and predict the postoperative morbidity and mortality. PMID- 2926978 TI - Hormonal and metabolic changes following severe head injury or noncranial injury. AB - In order to evaluate the effect of head injury in severely traumatized patients on the response of plasma cortisol, glucagon, insulin, glucose, and FFA as well as urinary N and catecholamines excretions, 36 patients were prospectively studied over 5 consecutive days following injury. They were divided into three groups: group I, severe isolated head injury (n = 14); group II, multiple injury combined with severe head injury (n = 12); group III multiple injury without head injury (n = 10). The results demonstrate similar hormonal and metabolic changes between these three groups of patients, characterized by elevated urinary adrenaline, noradrenaline excretion, increased cortisol, glucagon, insulin plasma levels throughout the study and elevated N urinary excretion with strongly negative N balances during the first 5 days postinjury. A significant correlation was observed between N intake and 5 day cumulated N balance (r = 0.63, p less than 0.001). In addition, N balance was negatively correlated with urinary excretion of adrenaline (r = -0.47, p less than 0.01) and noradrenaline (r = 0.44, p less than 0.05) as well as plasma levels of glucagon (r = -0.44, p less than 0.05). Isolated severe head injury seems to induce a full response in the secretion of the catabolic counterregulatory hormones comparable to that encountered in patients with multiple injury and associated with a marked increase in protein catabolism; additional noncranial major injury does not seem to enhance these responses. PMID- 2926979 TI - Serotonin metabolism in the central nervous system in portacaval shunted rats infused with fat emulsion. AB - Increased brain concentrations of tryptophan, and presumably thereby increased brain serotonin metabolism, have been observed following liver impairment and implicated in the etiology of portal-systemic encephalopathy (PSE). Increased plasma-free tryptophan (ie, not albumin-bound) concentrations can be expected after exogenous fat administration. This might further increase the brain serotonin metabolism in liver failure and negatively influence the PSE. We treated rats 2 weeks after end-to-side portacaval shunt (PCS) with continuous intravenous infusion of fat emulsion (Intralipid 20%) for 24 and 72 hr, respectively. The regional serotonin turnover was determined in different regions of the central nervous system (CNS) by measuring 5-hydroxyindole concentrations after NSD 1015 decarboxylase inhibition. The results revealed no further increase of the CNS serotonin turnover after fat infusion to PCS rats, compared with PCS rats given equal amounts of glucose. Thus, continuous infusion of a fat emulsion caused no major alteration of the CNS serotonin metabolism in PCS rats. PMID- 2926981 TI - [A histopathological investigation of metastatic liver tumors--the classification of their histological patterns and metastatic pathways taking into account the microscopic metastatic foci]. AB - A histopathological study of metastatic liver cancers has been performed on 433 autopsied cases at the Shikoku Cancer Center Hospital. With respect to the intrahepatic spread of the metastatic liver carcinomas, their invasion through the portal vein and the sinusoid were separately examined. The histological patterns of the prevalence of the liver metastasis were classified by taking into account both the factors and the prevalence of the nodules. A liver metastasis which was not detected by the naked eye but by microscopy was considered to be an early stage metastasis. All histological characteristics as well as the metastatic pathways also were considered. PMID- 2926980 TI - [Informing advanced cancer patients of the terminal nature of their disease and how this influenced their mental state]. AB - From January, 1983 to July, 1987, advanced cancer patients, who have since died, were analysed as to the influence of their mental state after being told of the terminal nature of their disease. After obtaining family consent, 27 out of total of 65 patients were told the true nature of their disease, in contrast to the remaining 38 terminal patients who were kept unaware that they had cancer on the insistence of their families. The depression observed just before death was the marker used to determine the patients' mental distress during the terminal period, and it was noted that the incidence of this terminal depression was higher in the uniformed patients, and highest in those with pain who had not been told. Thus it was concluded that informing a patient that he or she has terminal cancer does not always induce mental distress, even in patients in an advanced cancer stage. Further, the pain that cancer causes must be effectively fought, since this was the major cause of mental distress during the terminal stage of the disease. PMID- 2926983 TI - [Clinical experiences with intraluminal irradiation using 198Au grains in the treatment of bile duct carcinoma]. AB - Three cases of a bile duct carcinoma were treatment with radiotherapy, using intracatheterized 198Au grains. The intracatheter 198Au grains, placed in an inner tube, were inserted into a percutaneous transhepatic catheter. The number of 198Au grains used depended upon the length of the tumor. Tips of plastic were placed between the grains to improve the spatial and temporal dose allocation. The number of grains used can be changed quite easily, according to the length of the tumor, and the period of insertion in our cases was shorter than for a 192Ir wire. These three patients also received external irradiation and, since completion of treatment, two have continued to do well for the past 5 months. There have been no systemic or local complication. PMID- 2926982 TI - [The relative risk of a multiple primary cancer occurrence]. AB - Patients diagnosed with cancer of the stomach, colon, breast, and uterus at Kanagawa Cancer Center have been studied for the possibility of having multiple primary cancers. The total occurrence rates of a second primary cancer were 3.2% in men and 4.0% in women. The relative risk (RR) of man with cancer of the stomach showed a significantly heightened chance of developing cancer of colon (RR, 4.2), and women with cancer of the breast for developing cancer of lung (4.2) and of the opposite breast (8.5). Further women with an endometrial cancer had a high risk for developing a cancer of ovary (30.0). PMID- 2926984 TI - [Experiences in clinical application of an automated calculation system that determines the optimum intracavitary irradiation condition in the treatment of carcinomas of the uterine cervix]. AB - An automated calculation system that determines the optimum intracavitary irradiation condition for treating carcinomas of the uterine cervix has been developed on the basis of the Manchester system. Using Vax-11 computer, the system has been successfully applied in treating 105 patients since December, 1984. Trouble with the system almost occurred during its use in the first year of its clinical application. One problem related to the method of calculation, which was quickly settled, and the other was mainly a human error. The calculation system has proven especially useful for radiotherapists. PMID- 2926985 TI - [Combination chemotherapy using cyclophosphamide, adriamycin, and cisplatin in recurrent or advanced endometrial cancer--a preliminary report]. AB - Four patients with recurrent or advanced endometrial cancer have undergone combination chemotherapy with Cyclophosphamide, Adriamycin and Cisplatin (CAP). All drugs were administered by I.V. on day 1 in the following doses: Cyclophosphamide 500 mg/m2, Adriamycin 50 mg/m2 and Cisplatin 50 mg/m2. The treatment was repeated every 4 weeks and continued as long as there was disease progression. Two complete clinical responses and two partial responses were achieved. Based on these good results, we have initiated post-operative prophylactic chemotherapy using CAP in high risk patients. Adverse effects including myelo-suppression, nausea, and vomiting, and alopecia were seen in almost all patients. In no case, however, did any patient experience life threatening toxicity. Based on our experience, CAP therapy appears tolerable when used per our schedule. PMID- 2926986 TI - [Fast neutron radiotherapy of prostate cancer]. AB - Between 1976 and 1987, sixty eight patients suffering from prostate cancer were treated with fast neutron radiotherapy at the NIRS hospital in Chiba, Japan. Tumor doses of TDF 100 were administered to the prostate gland, the regional lymphnodes, and the true pelvis, using the two opposing fields by fast neutron alone or with a boost. The overall local or regional tumor recurrence rate was found to be 10% and local control seemed to correlate with the histological differentiation of the cancer tissue, though there was no definite correlation with hormone treatment. A relatively high incidence of grade 3 and 4 radiation complications were observed, 21% for grade 3 and 7% for grade 4, due to subcutaneous fat necrosis caused by an inferior dose distribution of the fast neutron machine. The 5-year survival rate was seen to be 52% in total and 70% for patients in stage C. The modality of radiotherapy for prostate cancer is discussed. PMID- 2926988 TI - [A case of coexistent adenocarcinoma and primary malignant lymphoma of the stomach]. AB - A case of a simultaneous adenocarcinoma and a primary malignant lymphoma of the stomach is presented. A sixty-one-year-old male was referred to us with epigastralgia. Gastroscopy and a biopsy revealed a *** c-like lesion in the stomach and, on histological examination, was determined as being an adenocarcinoma. A proximal gastrectomy and an R2-resection of lymph nodes then was performed. A pathological examination of the resected stomach disclosed a malignant lymphoma neighboring the adenocarcinoma. The presence of a simultaneous carcinoma and a malignant lymphoma of the stomach is quite rare, with only twenty eight documented patients reported in the Japanese literature. This entity is discussed. PMID- 2926989 TI - [A case of asbestosis complicated with double cancer of the stomach and colon]. AB - A case of a double cancer, a stomach and a colon cancer, in a 84-year-old man is reported. The patient had an occupational history of asbestos exposure while working at two shipyards. His chest X-ray revealed typical, pleural plaque with calcification. Further, a significant number of asbestos bodies in his autopsied lung tissue was detected. In spite of failure to detect asbestos bodies in the stomach and the colon, our findings suggest that these two cancers may have been induced by asbestos exposure. PMID- 2926991 TI - [Manual for pre- and postoperative patient care. Brain tumor]. PMID- 2926990 TI - [A pleomorphic lipoma of the palm--comparison to spindle cell lipoma]. AB - A pleomorphic lipoma usually occurs in the neck, the shoulder, and/or on the backs of men over the age of 50. This tumor displays a mixture of fat cells, pleomorphic cells, floret cells, and bundles of mature collagen fiber. Herein we report on a pleomorphic lipoma that occurred on the palm of a 56-year-old woman. An immunohistochemical study, performed to compare the characteristics of a pleomorphic lipoma with those of a spindle cell lipoma, has suggested that the pleomorphic and floret cells of a pleomorphic lipoma are similar to the spindle cells of a spindle cell lipoma and not to fat cells. Our result seems to indicate that these two tumors are on the same spectrum and only the quantity of the pleomorphism keeps them distinct. PMID- 2926987 TI - [A case of retrocecal appendicitis occurrence during effective chemotherapy in lung cancer]. AB - Reported is the case of 61-year-old male patient who developed an abscess, secondary to a ruptured retrocecal appendicitis, while undergoing effective chemotherapy for lung cancer. Patients undergoing cancer chemotherapy are especially susceptible to infectious complications because chemotherapy can cause myelosuppression. To our knowledge, has been no previous reported case of retrocecal appendicitis occurring during chemotherapy for the lung cancer. Retrocecal appendicitis is a dangerous form of complication occurring in patients being treated with chemotherapeutic drugs. PMID- 2926992 TI - [Manual for pre- and postoperative patient care. Hydrocephalus]. PMID- 2926993 TI - [Manual for pre- and postoperative patient care. Lung cancer]. PMID- 2926994 TI - [Manual for pre- and postoperative patient care. Breast cancer]. PMID- 2926995 TI - [Manual for pre- and postoperative patient care. Pharyngeal cancer]. PMID- 2926996 TI - [Manual for pre- and postoperative patient care. Esophageal cancer]. PMID- 2926998 TI - [Manual for pre- and postoperative patient care. Thyroiditis (Basedow's disease)]. PMID- 2926997 TI - [Manual for pre- and postoperative patient care. Stomach cancer]. PMID- 2926999 TI - [Manual for pre- and postoperative patient care. Uterine cancer]. PMID- 2927000 TI - [Manual for pre- and postoperative patient care. Chronic rheumatoid arthritis]. PMID- 2927001 TI - [Manual for pre- and postoperative patient care. Fractures]. PMID- 2927002 TI - [Manual for pre- and postoperative patient care. External injuries (upper and lower extremity amputation)]. PMID- 2927003 TI - [Manual for pre- and postoperative patient care. Cataract]. PMID- 2927004 TI - [Trends in evaluation nursing research in the U.S.A. 2. Research findings organized by model variables]. PMID- 2927005 TI - [Trends in evaluation nursing research in the U.S.A. 3. Evaluative research in practice: an example]. PMID- 2927006 TI - [Evaluation nursing research in nursing practice. II. Issues and possibilities of evaluation research for nursing. 4. Computer technology and evaluation research]. PMID- 2927007 TI - [Issues and possibilities of evaluation research for nursing. 5. Ethics and evaluation research]. PMID- 2927008 TI - [Issues and possibilities of evaluation research for nursing. 6. Research utilization: will it change practice?]. PMID- 2927009 TI - [Issues and possibilities of evaluation research for nursing. 7. Nature and goal of nursing practice]. PMID- 2927010 TI - [Issues and possibilities on evaluation research for nursing. 8. Summary]. PMID- 2927012 TI - [Evaluation nursing research in nursing practice. III. Process of conducting evaluation research. 9. Three column approach to generating researchable problems]. PMID- 2927011 TI - [Evaluation nursing research in nursing practice. I. Trends in evaluation nursing research in the U.S.A. 1. Definition and conceptualization of the model]. PMID- 2927014 TI - [Process of conducting evaluation research. 11. Research methodology: sampling and instruments]. PMID- 2927013 TI - [Process of conducting evaluation research. 10. Selecting a research design]. PMID- 2927015 TI - [Process of conducting evaluation research. 12. Summary]. PMID- 2927016 TI - Proceedings: 62nd general meeting, Japanese Pharmacological Society. March 25-28, 1989, Kyoto, Japan. Abstracts. PMID- 2927017 TI - Inhibition by gossypol of cyclic nucleotide-independent phosvitin kinase from pig testis. AB - Gossypol, a male anti-fertility agent, was found to be an inhibitor of cyclic nucleotide-independent phosvitin kinase from pig testis. The IC50 value (concentration causing 50% inhibition) was 42 microM using phosvitin as substrate. Kinetic analysis indicated that the compound inhibited the enzyme noncompetitively with respect to ATP (Ki = 17 microM) and competitively with respect to phosvitin (Ki = 11 microM). The gossypol inhibition was reversed by the addition of polyamines. The compound also inhibited phosphorylation of high mobility group (HMG) proteins HMG 14 and 17 (the endogenous substrates in the testis located in nucleosome), with an IC50 value of 48 microM. PMID- 2927018 TI - Oral flora of mongrel and beagle dogs with periodontal disease. AB - The plaque flora was studied in adult mongrel and beagle dogs with periodontal disease. Gingival plaque from maxillary premolars was removed and cultured on various growth media. The flora in all dogs was composed of mostly anaerobic gram negative rods. Bacteroides asaccharolyticus was found in the highest proportion of plaque samples from mongrel dogs, and decomposed hydrogen peroxide suggesting catalase activity. Fusobacterium nucleatum was found in higher proportion in the plaque of beagle dogs as compared to B. asaccharolyticus. With the increasing numbers of obligative anaerobic gram negative organisms such as B. asaccharolyticus, the proportions of Streptococcus, Enterococcus and Staphylococcus decreased in the dogs with periodontal disease. The salivary flora was different from the plaque flora of the dogs with periodontal disease. It was constant regardless with the disease. The salivary flora of beagle dogs with the healthy gingiva was different from that of mongrel dogs. Enterococcus, Lactobacillus, Eubacterium and black-pigmented Bacteroides (BPB, mainly B. asaccharolyticus) were higher proportion in the flora of beagle dogs as compared to mongrel dogs, while Fusobacterium, Enterobacteriaceae, yeast and molds were lower in the flora. The results reveal that B. asaccharolyticus and F. nucleatum are common pathogens and uniquely contribute to the development of gingival inflammation in dog. PMID- 2927019 TI - Effects of isoprothiolane and phytosterol on serum lipids and adipose tissue of rats given saturated fat diet. AB - Rats received hardened-tallow (HT) diet continuously for 18 weeks. After 8 weeks of feeding, isoprothiolane (50 mg/kg) or phytosterol (20 mg/kg) was administered orally to the rats once a day consecutively for 10 weeks. In the rats given isoprothiolane, serum high density lipoprotein (HDL) phospholipid concentration increased. Decreased serum very low density lipoprotein (VLDL) cholesterol concentration was seen in the rats given phytosterol. Isoprothiolane increased the level of palmitoleic acid (16:1), while phytosterol increased the level of palmitic acid (16:0) in phospholipid of adipose tissue. In the frozen tissue sections, the multiple crystals were seen in fat cells of the rats fed HT diet. Less crystals were seen in the rats given either drug when compared with the rats fed HT diet without drug. PMID- 2927020 TI - Cellular injury and lipid peroxidation induced by hexavalent chromium in isolated rat hepatocytes. AB - In order to elucidate the relationship between cellular injury and lipid peroxidation induced by hexavalent chromium (CrVI), isolated rat hepatocytes treated with any one of scavengers of active oxygen species, antioxidants or antichromium agent were incubated with K2Cr2O7 as CrVI (1 mM Cr). After the incubation, the development of lipid peroxidation was determined as thiobarbituric acid (TBA)-reacting materials in total lipid extracts from the incubated hepatocytes. Cellular injury was observed as a leakage of lactate dehydrogenase (LDH) from hepatocytes into incubation medium. The contents of reduced glutathione (GSH) in hepatocytes were also assessed. Results obtained were as follows: (1) CrVI facilitated lipid peroxidation in isolated hepatocytes after 20 min of incubation. On the other hand, the cellular injury induced by CrVI was barely observed even after 60 min of incubation. (2) The CrVI-induced lipid peroxidation was inhibited by catalase and mannitol as scavengers of active oxygen species, or N,N'-diphenyl-p-phenylenediamine and alpha-tocopherol as antioxidants. However the cytotoxicity of CrVI could not be prevented by these chemicals. (3) CrVI depleted the contents of intracellular GSH and diminished the activities of glutathione reductase (GR) and glutathione-S-transferase (GST) except glutathione peroxidase. (4) The scavengers of active oxygen species and the antioxidants could not prevent the depletion of intracellular GSH induced by CrVI. (6) Ascorbic acid, antichromium agent, prevented all of the lipid peroxidation, the cellular injury and intracellular GSH depletion induced by CrVI.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2927021 TI - Experimental induction of splayleg in piglets by pyrimethamine. AB - Dietary administration of 3.6 mg/kg (BW)/day of pyrimethamine (PYR) to the 10 pregnant Goettingen minipigs for the 1st quarter (during days 11 to 16) or the 2nd quarter (during days 17 to 22) of the organogenetic period elicited the congenital splayleg (CSL) in 20 out of 27 live newborns. Only a splayleg piglet out of 18 was found in the control group. The incidence of stillbirth was higher in the PYR groups than the control group, but no major external malformation was observed in the piglets of the PYR groups. Histological and biochemical examinations of the muscles from the hindleg, foreleg and truncus were carried out. The severity of myofibrillar hypoplasia depended on neither CSL symptoms nor PYR administration. Although a significant decrease of protein content of the muscles was observed in the piglets of the PYR groups, the mechanism underlying the pathogenesis of induced splayleg was obscure. PMID- 2927022 TI - Artificial infection by transplantation of juvenile Fasciola worms into the abdominal cavity of rats. AB - Rats were successfully infected with Japanese Fasciola sp. by transplantation of juvenile worms (JW) or metacercariae (MC) into the abdominal cavity. Moreover, the rat was investigated on its suitability for different experiments with liver flukes. JWs or MCs transplanted intraperitoneally (IP) matured in the bile duct of rats. Moreover, more stable infections were established by inoculation of JWs than MCs. About 3 of 10-15 JWs transplanted into the abdominal cavity of a rat matured and laid eggs in the bile duct. The mean prepatent period was 63.5 days in the JW inoculated group. EPG values were kept constant at a level of 10(2) 10(3) about 100 to 230 days after the transplantation of JWs. The life span of Japanese liver flukes was estimated to be about 400 days in rats. From these results, it was concluded that the rat is suitable for various experiments with Fasciola sp. PMID- 2927023 TI - Eimeria capricornis n.sp., E. nihonis n.sp., E. naganoensis n.sp., and E. kamoshika n.sp. (Protozoa: Eimeriidae) from the Japanese serow, Capricornis crispus. AB - Eimeria capricornis n.sp., E. nihonis n.sp., E. naganoensis n.sp. and E. kamoshika n.sp. were detected from the Japanese serow, Capricornis crispus. The oocysts of these species were ovoid to ellipsoid, measuring 48.02 +/- 0.53 x 33.93 +/- 0.35 microns, 29.73 +/- 0.45 x 21.01 +/- 0.29 microns, 20.04 +/- 0.05 x 15.77 +/- 0.04 microns and 30.02 +/- 4.24 x 14.58 +/- 2.03 micron, respectively. In all the species the micropyle was observed, but the micropylar cap and oocyst residuum were not present. The polar granules were observed in the oocysts of E. capricornis. The sporocysts of the above species were spherical to elongate ovoid, measuring 15-23 x 8-13 microns, 14-16 x 7-10 microns, 11-13 x 6-8 microns and 8-10 x 6-7 microns, and the sporulation time was 6, 3, 3 and 6 days, respectively. The sporocyst residuum and refractile body were seen in all the species. In the sporocysts of E. naganoensis and E. kamoshika tiny Stieda body was seen, but not in the other two species. These four Eimeria species were not infective to goats. PMID- 2927024 TI - Possible role of plasma neurotensin in regulating the excitatory neural control of the rectum of the fowl. AB - Effects of neurotensin (NT) applied via the blood vessel on the responses to stimulation of Remak's nerve (RNS) were investigated in the chicken isolated and perfused rectums. NT (5 ng-2 micrograms/ml) produced a concentration-dependent inhibition of the constituent contraction but not relaxation of the responses to RNS. In addition, high concentrations of NT (over 80 ng/ml) produced a contraction of the rectal muscle. Propranolol, a beta-adrenoceptor blocking agent, and guanethidine, an adrenergic neurone blocking agent, were able to reduce the inhibitory effect of NT on the response to RNS while potentiating the contractile effect of NT on the rectal muscle. NT (0.1 and 1 microgram/ml), like norepinephrine, decreased the flow rate of perfusate from the isolated rectum which was perfused at a constant pressure. Guanethidine enhanced norepinephrine induced vasoconstriction, and phentolamine, an alpha-adrenoceptor blocking agent, plus propranolol was able to abolish it. Either of these prior applications resulted in a small but significant reduction of NT-induced vasoconstriction. These findings suggest that NT in plasma may function as a circulating hormone to exhibit an inhibitory action on the excitatory neural input to the rectum in the chicken, and that catecholamine release from adrenergic nerve terminals by NT may account for some but not all of the activity. PMID- 2927026 TI - An application of the image analyzer to the soft radiogram of the third metacarpus in horses. PMID- 2927025 TI - An improved method for hemagglutinin extraction from feline herpesvirus type 1 infected cell line. AB - Hemagglutination (HA) activity of feline herpesvirus type 1 (FHV-1) propagated in feline lung cell culture and two established feline cell lines, CRFK and fcwf-4, was investigated. Intra- and extracellular crude samples obtained from those infected cell cultures did not show HA activity. However, when treated with tween 80-ether, HA activity appeared. There was no correlation between virus infectivity titers and the HA titers at various harvesting times, and besides, hemagglutinins were found in intracellular samples at the early stage of infection. By ultrasonic destruction of the infected fcwf-4 cells, high titer hemagglutinins were obtained. High titer hemagglutinins were also extracted successfully from infected fcwf-4 cell membranes by solubilization with any of the three detergents: Triton X-100, DOC, and CHAPS. The optimal concentrations of each detergent for solubilizing hemagglutinin were 0.05 (v/v)%, 0.5 (w/v)%, and 0.1-0.2 (w/v)%, respectively. The HA activities of both the ultrasonic-treated hemagglutinin and the detergent-soluble hemagglutinin from infected fcwf-4 cells were inhibited specifically by anti-FHV-1 sera. Therefore, either hemagglutinin could be used as HA antigen for the hemagglutination-inhibition test. PMID- 2927027 TI - Ulex europaeus agglutinin I binding in the apocrine glands of the interdigital gland and skin in the Japanese serow Capricornis crispus. PMID- 2927028 TI - Protothecal mastitis in a cow. PMID- 2927029 TI - An adhesion-hemadsorption test for screening and identification of Mycoplasma gallisepticum. PMID- 2927030 TI - Diplotriaena falconis (Connal, 1912) (Filariidae, Nematoda) from a red-legged falconet, Microhierax caerulescens. PMID- 2927031 TI - A successful case of spastic paresis in a calf by partial tibial neurectomy. PMID- 2927032 TI - A case of chronic diffuse uveitis accompanied with dermal depigmentation in Akita dog. PMID- 2927033 TI - An evidence for human tumor cell lines producing different carcinoembryonic and/or its related antigens. PMID- 2927034 TI - Parasternal congenital diaphragmatic hernia in a calf. PMID- 2927035 TI - Selective binding of leukemia and lymphoma cell lines to lectins. PMID- 2927036 TI - Relation of intrinsic heart rate and autonomic nervous tone to resting heart rate in the young and the adult of various domestic animals. AB - Intrinsic heart rate (IHR) and autonomic nervous tone (ANT) were measured using the young and the adult of horses, cows, pigs, goats and chickens in order to elucidate species differences in a decrease of resting heart rate (RHR) with growth or age. The IHR and ANT were estimated from the changes in heart rate after the administration of atropine and/or propranolol. The IHR in all species decreased progressively with an increase in body weight from young to adult, and moreover the ANT altered toward the direction of parasympathetic predominance by a decrease in sympathetic tone and/or an increase in parasympathetic tone. The decrease of the RHR with growth resulted from a decrease in the IHR primarily and from a parasympathetic predominance in the ANT secondarily. A considerable species difference existed in the alteration of the ANT. PMID- 2927037 TI - Plasma prolidase activity as a possible diagnostic index of chronic hepatic abscess in cattle. AB - The usefulness of prolidase as a biochemical parameter to represent the chronic state of hepatic abscess was discussed in eight cattle experimentally inoculated with Fusobacterium necrophorum and 18 spontaneously affected cattle. Blood was daily collected to measure the plasma prolidase activity and sialic acid level from the experimental cattle for 90 days after inoculation. In three out of four cattle affected with hepatic abscess, prolidase activity began to rise about 40 days after inoculation, and maintained high activity till 90 days. In the same cattle the sialic acid concentration increased from 7 to 10 days after inoculation, and gradually returned to the normal value 50 days after it. Another cow showed a similar change in early stage of experiment, but prolidase activity decreased after 70 days and sialic acid concentration maintained high level till 90 days. In two cattle, which showed scars but no abscess on autopsy, the prolidase activity increased temporarily from 40 to 55 days after inoculation. In the control cattle inoculated with an inactivated bacterial suspension, neither the sialic acid level nor the prolidase activity showed any large variation in the experimental period. Among the spontaneously affected cattle, those with a high sialic acid level revealed normal prolidase activity and those with a normal sialic acid level had high prolidase activity. PMID- 2927038 TI - Studies on serum selenium and tocopherol in white muscle disease of foal. AB - In order to clarify the cause of white muscle disease (W.M.D.) in foals, tocopherol and selenium concentrations in serum and glutathione peroxidase activities in blood were measured. Examination was made on the samples from horses affected with W.M.D., the foal kept with them in the same stable, the foals kept in the stables without affected foals, and respective mares. The heavy breed horses in Fukuoka prefecture and Tokachi district were also examined for comparison. Serum tocopherol levels of these foals were normal because after intake of colostrum. Mares of affected foals showed lower tocopherol levels than other examined mares (p less than 0.01). Serum selenium levels of all foals were below 65 ppb, showing deficient levels. The mares of affected foals had lower selenium levels than other mares (p less than 0.01). There was a good correlation between serum selenium concentration and blood glutathione peroxidase activity (r = 0.81). Selenium levels in the liver of affected foals were lower than the foals which succumbed with other diseases. Diet supplied in the stables with affected foals showed low alpha-tocopherol and selenium contents. These findings suggest that W.M.D. in foals is attributed to nutritional muscular dystrophy caused by tocopherol and selenium deficiency of their mares in late gestation period. PMID- 2927039 TI - Formation of male and female sex cords in gonadal development of C57BL/6 mouse. AB - The sex cords of male and female fetal C57BL/6 mice were studied by light and transmission electron microscopy to elucidate the origins of Sertoli cells (male) and follicle cells (female) in detail. In the testes of fetal mice from day 12 to day 14 post coitum (p.c.), PAS-positive substances were detected exclusively throughout the cytoplasm of Sertoli cells. On day 12 p.c., pre-Sertoli cells, identified by PAS-reaction, formed irregular and cord-like arrangements around germ cells. The arrangements were not associated with the coelomic epithelium. Thus, it is suggested that Sertoli cells are originated from the mesonephric tissues. In the ovaries, germ cell cords were still not observed at a stage immediately following the gonadal sex differentiation in male. On about day 15 p.c., connective tissues including many capillaries penetrated into the ovaries, resulting in obvious formation of germ cell cord-like arrangements. At the same time, the coelomic epithelium-derived cells (CEd cells) as well as the mesonephros-derived cells (Md cells) invaded the adjacent arrangements. It is concluded that the follicle cells are originated most from Md cells and some from CEd cells. PMID- 2927040 TI - Clinical and biochemical findings in bovine cerebrocortical necrosis produced by oral administration of amprolium. AB - Purposing to get some hints on cause and early diagnosis for cerebrocortical necrosis (CCN), CCN was produced in three healthy calves by the oral administration of amprolium. All three calves showed central nervous signs characterized by ataxic gait, clonic spasm, astasia and opisthotonus, from 24 to 49 days after the start of daily administration of 321-418 mg/kg amprolium. They showed bradycardia from about 20 days before the appearance of the nervous signs, which was supposed to be a finding of primary change and to be useful for early diagnosis of CCN. At necropsy of the two calves, large necrotic lesion was found in the cerebral cortex, and tissue thiamine levels decreased significantly, especially in cerebrum and cerebellum. In the other calf, injection with 25 mg thiamine tetrahydrofurfuryl disulfide (TTFD) was proved to be effective for the recovery of clinical signs. No significant changes in thiamine level were recorded in the whole blood, but those in erythrocytes decreased slightly at about a week before the appearance of the clinical signs. No significant alteration of thiamine excretion was observed in urine. Those findings suggest that CCN in calves is caused by thiamine deficiency and that the blood thiamine levels cannot be used for diagnosis of CCN. PMID- 2927041 TI - Role of lymphocytes in dogs experimentally re-challenged with canine transmissible sarcoma. AB - The role of lymphocytes in dogs re-challenged with canine transmissible sarcoma (CTS) was investigated histologically and immunologically. Tumors were detected on the 3rd day, began to regress on the 9th day and disappeared on approximately the 15th day after the secondary transplantation (AST). The CTS cells were surrounded by lymphocytes which had infiltrated from the early stage, degenerated and ultimately disappeared. Most of the lymphocytes expressed thymocyte antigen (Ta) on the cell membrane surface. The numbers of lymphocytes and Ta-positive lymphocytes in peripheral blood increased gradually AST. The blastogenic responses of peripheral blood lymphocytes (PBL) induced by 3 kinds of mitogens were elevated strikingly from the early stage AST. These results suggest that Ta positive lymphocytes play an important role in vivo in the regression of tumors and that the immunological activity of PBL is stimulated immediately AST. PMID- 2927042 TI - Evaluation of the pathogenicity and immunogenicity of vaccinia virus to piglets. AB - The pathogenicity and immunogenicity of vaccinia virus were examined in order to evaluate the possibility of its application as a recombinant viral vaccine in pigs. Following scarification inoculation with vaccinia virus, a mild reddish papulation developed only on the scarified part of the skin. No symptoms of illness such as fever or stunting were noted. Vaccinia virus was recovered in titers from scarified skin 4 and 7 days after inoculation. Control piglets cohabited with inoculated animals remained normal for the whole 5 week observation period. Hemagglutination inhibition and indirect immunofluorescence tests detected antibodies against vaccinia virus in the inoculated piglets, whereas no anti-vaccinia virus antibodies were detected in the contact control animals. Antigen-induced blastogenic tests of peripheral blood lymphocytes from animals, revealed that lymphocytes obtained from inoculated donors 5 weeks after inoculation, had a higher stimulation index (P less than 0.05) than did those from uninoculated piglets. These results suggested that vaccinia virus would be useful as a recombinant viral vector for pigs. PMID- 2927043 TI - Kansas responds to AIDS. PMID- 2927044 TI - Professional nursing making the big mental leap--what was to what is to what will be. PMID- 2927045 TI - Update: universal precautions for prevention of transmission of human immunodeficiency virus, hepatitis B virus, and other bloodborne pathogens in health-care settings. PMID- 2927046 TI - School nursing and AIDS education. PMID- 2927047 TI - Phospholipase A: recent developments in methodology, pathophysiology and clinical application. Papers from a workshop. June 1988, Ulm, Federal Republic of Germany. PMID- 2927048 TI - Time-resolved fluoroimmunoassay of pancreatic phospholipase A2. AB - We have developed an immunoassay for human pancreatic secretory phospholipase A2 based on time-resolved fluorescence. The labeled antibody technique in combination with the time-resolved fluorometric detection of the Europium label, which essentially eliminates all background fluorescence, resulted in a high sensitivity and a wide linear range. Our assay is a one-incubation, multi-site, solid-phase assay on polystyrene microtiter strips, even though a polyclonal antibody was used. Increased levels of immunoreactive phospholipase A2 are found by this assay in sera of patients suffering from acute pancreatitis. PMID- 2927049 TI - Modified photometric method for the determination of phospholipase A activities. AB - A modified photometric method for the determination of phospholipase A activities which is based on a previously published reaction principle is described. The modified assay uses a lyophilized substrate emulsion rather than a freshly prepared phospholipid emulsion and a new chromogen (tribromohydroxybenzoic acid and 4-amino-antipyrine) with a high molar absorption coefficient (1,930 m2/mol at 546 nm, 2,900 m2/mol at 512 nm wavelength). The new test is more practicable with respect to pipetting volumes and incubation times. Preliminary results of a method evaluation indicate that the modified assay fulfills the usual criteria for clinical chemical enzyme measurements. PMID- 2927050 TI - A radiochemical test for phospholipase A2 catalytic activity. AB - A position-specifically labelled phosphatidylcholine is the substrate for the selective determination of Phospholipase A2 in serum, ascites and tissue samples. Optimal reaction conditions and simplifications of handling are discussed. A control group of human serum samples ranged up to 2.1 U/l. The maximum serum activity in samples of patients with acute pancreatitis was 126 U/l. In human ascites activities up to 380 U/l were measured. The method described here turned out to be a practicable instrument for the determination of phospholipase A2 activity using only commercially available reagents. PMID- 2927051 TI - Characterization of phospholipase A2 activity in aspirates of human pancreatic pseudocysts after isolation by reversed-phase high performance liquid chromatography. AB - Phospholipase A (PLA) is able to attack membrane phospholipids and thereby plays a putative role in the pathogenesis of pancreatic pseudocysts. We looked for PLA2 like activity in aspirates from human pancreatic pseudocysts. In material originating from one cyst which occurred shortly after an acute pancreatitis attack, hydrolyzing enzymatic activity measured by a sensitive bioassay system for PLA2 activity was found without prior trypsin activation (67 x 10(3) U/min/100 microliters). A biochemical characterization of this hydrolyzing enzymatic activity was provided after resolution of the respective proteins contained in the cyst fluid by HPLC. High hydrolyzing activities were found in correspondence to one specific, early eluting peak. The purified enzyme had pH optima at 3.5 and 6. Addition of EDTA (5 mM) to the test system abolished the enzymatic activity which mirrored the requirement for calcium ions. The activity was optimal at calcium concentrations ranging from 1-2 mM. Higher calcium concentrations reduced the enzymatic activity. The enzyme showed high heat stability. SDS-gel analysis of the peak showed one single band with a molecular weight of about 20,000 Daltons. Our findings demonstrate the possibility of activated, PLA-like activity in human pancreatic pseudocyst fluid. We speculate that an inappropriate activation of this enzyme in peri- or intrapancreatic "fluid collections" could account for pseudocyst formation after an acute pancreatitis attack. PMID- 2927052 TI - Phospholipase A activities in ascites, serum, lymph, and urine in acute pancreatitis following pancreas stimulation with secretin-ceruletid. AB - As a result of pancreas stimulation with secretin-ceruletid we were able to measure the release of phospholipase A in ascites, serum, lymph, and urine in acute experimental pancreatitis in the dog. After induction of acute pancreatitis we found no increase over the normal range in serum, lymph, and urine phospholipase A activities. In addition, the stimulation of the exocrine pancreas did not show a significant change in phospholipase A activity. The excessively high phospholipase A activity in ascites following induction of acute pancreatitis fell significantly after pancreas stimulation with secretin ceruletid. PMID- 2927053 TI - Phospholipase A2--regulation and inhibition. AB - Phospholipase A2 (PLA2) has been implicated in the pathogenesis of different diseases. Thus, the pharmacological intervention of PLA2 activity by specific inhibitors is of great therapeutical value in ameliorating pathological conditions. Despite a great number of published data regarding PLA2 inhibitors none has reached clinical application. Since enzyme activity can be greatly influenced by the experimental conditions of the test system used, a potent in vitro enzyme inhibitor does not indicate therapeutic effectiveness per se. In order to enhance the predictable value of an in vitro screening system for PLA2 inhibitors, a battery of test systems each measuring certain parameters should be applied. Considering the complex mechanism(s) of PLA2 it is extremely important to elucidate the exact inhibition mechanism of those compounds, which have passed these first filters. True inhibitors of PLA2 should then be evaluated in suitable ex vivo, in vivo models. PMID- 2927054 TI - Phospholipase A2 induced diffuse alveolar damage--effect of indomethacin and dexamethasone upon morphology and plasma-histamine level. AB - Phospholipase A2, injected as a bolus into the jugular vein of adult male Wistar rats was investigated with respect to its action upon lung morphology and blood- plasma- histamine. In comparison with the injection of saline, phospholipase A2 causes hyperemia of the lungs, sequestration of granulocytes and intraalveolar pulmonary edema; the histamine level is increased to the sixfold. Pretreatment of the animals with indomethacin diminishes the toxic effect of phospholipase A2 upon the lungs and the histamine level. PMID- 2927055 TI - Prognostic value of serum phospholipase A in acute pancreatitis. AB - Serum from 48 patients with acute pancreatitis (21 with interstitial-edematous and 27 with necrotizing pancreatitis) was monitored for immunoreactive (IR) phospholipase A2 (PLA2) protein concentration and PLA catalytic activity. In both groups within 48 h after start of acute pancreatitis an up to tenfold increase of IR-PLA2 was demonstrable. Determination of IR-PLA2 revealed no differences between the groups. In contrast, determination of PLA catalytic activity allowed us to differentiate between patients with interstitial-edematous and necrotizing pancreatitis. PMID- 2927056 TI - Prognostic value of serum phospholipase A in the multitraumatized patient. AB - Phospholipase A serum activity was prospectively studied in 39 patients with multiple trauma. There was no correlation of phospholipase A activity with type or severity of injury. With increasing phospholipase A levels, a rise in mortality was found. A prediction of fatal outcome on an individual basis was not possible. The sensitivity for complications was 90%, whereas the predictive value of the positive test (64%) and specificity (47%) were low. When the behavior of phospholipase A and elastase release were compared, no correlation between these two parameters could be detected. Therefore, PMN leukocytes do not seem to be a major source of phospholipase A in serum. PMID- 2927057 TI - Phospholipase A--a parameter of sepsis? A comparison of PLA and Stevens' Sepsis Severity Score. AB - Phospholipase A (PLA) and Sepsis Severity Score (SSS) were measured regularly in 28 patients with sepsis (n = 11), pancreatic operations (n = 7), or multitrauma combined with contused abdominal trauma (n = 10). No linear correlation was found between these two parameters. A statistical correlation could be shown for the paired values PLAmax/SSS or PLA/SSSmax. They lie together above or below their "critical value" of 20 points SSS or 30 U/l PLA (alpha less than 0.05). The evaluation of mortality shows a distinctly higher significance for the SSS (P less than 0.01) in comparison with the PLA (P less than 0.05). In certain cases PLA was the first parameter which could have shown the beginning of a septic process. PMID- 2927058 TI - Serum phospholipase A2 in intensive care patients with peritonitis, multiple injury, and necrotizing pancreatitis. AB - To study the source and role of circulating phospholipase A2 (PLA2) catalytic activity we monitored the serum from patients with necrotizing pancreatitis (n = 8), diffuse peritonitis (n = 6), and multiple injuries (n = 11). Immunoreactive PLA2 serum protein concentration was analysed using a fluoroimmunoassay based on an antibody against human pancreatic PLA2. Serum PLA2 catalytic activity was analysed using a radiochemical method based on a substrate with tritiated palmitic acid in beta position. In necrotizing pancreatitis immunoreactive PLA2 and PLA2 catalytic activity both increased. Obviously, in necrotizing pancreatitis the major part of serum catalytic activity stems from the pancreas. In patients with diffuse peritonitis and multiple injuries, as a rule, immunoreactive phospholipase A2 serum concentration appears to be within the normal range. In contrast, in these patients we demonstrated high serum catalytic PLA2 activity comparable to that in necrotizing pancreatitis. The source of catalytic PLA2 activity in peritonitis and multiple injuries seems not to be the pancreas. There was a correlation between pulmonary insufficiency and serum PLA2 catalytic activity in patients with necrotizing pancreatitis, peritonitis, and multiple injuries. PMID- 2927059 TI - Serum phospholipase A in hematological diseases. AB - Inflammatory cells, e.g., neutrophils, monocytes, and macrophages are presumed to be a source of circulating phospholipase A in nonpancreatic diseases. Therefore, we investigated in a preliminary study whether serum phospholipase A activity is related to leukocyte counts in 43 patients with hematological diseases. Serum PLA activity was significantly increased in patients with Hodgkin's disease, acute monocytic leukemia, myelofibrosis with myeloid metaplasia, and polycythemia vera when compared with patients with chronic myelogenous leukemia, chronic lymphocytic leukemia, and acute myelogenous leukemia, but did not correlate with total leukocyte counts. PMID- 2927060 TI - Increased platelet volume--sign of impaired thrombopoiesis in diabetes mellitus. AB - Increased functional properties of diabetic platelets might be already conditioned during thrombopoiesis in the stem cell system. This hypothesis was studied by recording the distribution characteristics of the peripheral platelet pool in 218 diabetic patients versus 51 controls. Furthermore, platelet membrane coating with the stem cell marker glycoprotein IB was analyzed in 41 diabetic subjects and compared to 23 healthy volunteers. A consistent, significant shift of the volume distribution to larger platelets was found in diabetics: Mean platelet volume (MPV) - 7.9 +/- 0.9 versus 7.2 +/- 0.8 [fl]; Megathrombocyte index (MTI) - 20.4 +/- 2.8 versus 18.1 +/- 2.5 [fl]. These deviations were present in all patient subsets, however did not correlate to parameters of glucose metabolism. Whole blood platelet count was increased in the patient group; 195.0 +/- 59.5 versus 184.0 +/- 37.5 x 10(3) plts/ul. Coating with glycoprotein IB receptors correlated significantly to platelet size in platelets of both controls and diabetics (r normal = 0.52 +/- 0.07; r diabetic = 0.46 +/- 0.1). The quantitative expression of glycoprotein IB was significantly enhanced in the diabetic group: 54,500 x 1.28 +/- 1 versus 39,100 x 1.3 +/- 1 molecules per platelet. In conclusion, these findings strongly support the assumption of diabetic stem cell dysfunction of the megakaryocytic series and progenitor cells resulting in platelets with primarily increased potency to adhere and aggregate in diabetes mellitus. PMID- 2927061 TI - [Progressive multifocal leukoencephalopathy in Wegener's granulomatosis in relation to therapy with cyclosporin A]. AB - A female patient with Wegener's granulomatosis developed severe bone marrow depression after two years treatment with cyclophosphamide. Corticosteroids alone could not sufficiently suppress disease activity, therefore additive therapy with Cyclosporin A was started. Four weeks later the patient developed a central nervous system disorder with affective disturbances and progressive somnolence. However, inspite of intensive diagnostic procedures, no definite diagnosis could be established. After another two months she died. Post-mortem-examination showed progressive multifocal leukoencephalopathy. An association between immunosuppressive therapy and reactivation of JC-Virus is suggested. PMID- 2927063 TI - [Developmental tasks of the elderly from a psychosocial aspect]. PMID- 2927062 TI - [Innovative aspects in clinical medicine. Nephrology--new perspectives for dialysis patients. Symposium. 25-27 November 1988, Heidelberg. Abstracts]. PMID- 2927064 TI - [Survey report on nursing education, 1988]. PMID- 2927065 TI - [Role of public health nurses in a health center]. PMID- 2927066 TI - [Role of the occupational nurse based on the worker's health status in Korea]. PMID- 2927068 TI - [Nursing diagnosis in wellness childbearing settings]. PMID- 2927067 TI - [Crisis theory: the foundation of the function of public health centers]. PMID- 2927069 TI - [Case study of a patient with liver cirrhosis]. PMID- 2927070 TI - [A study comparing the perception of patients, nurses and doctors about the educational needs of cancer patients]. AB - Because of the advances in the treatment of cancer, patients live longer and require more comprehensive information in order to understand their illness, treatment procedure and role in the health care process. Each treatment involves combined therapeutic approaches, so information must be presented to the patient in such a way as to promote maximum understanding and acceptance. The purposes of this study were to explore and compare patients', nurses' and doctors' perception of the educational needs of cancer patients and to identify areas of agreement and disagreement in the perception of these needs by patients, nurses and doctors. Three groups took part in the study; 78 cancer patients, 39 nurses and 35 doctors. They all were selected from one general teaching hospital. Data were collected using a questionnaire, developed by the investigators. The questionnaire was made up of 2 sections; an importance rating scale and a knowledge/providing information rating scale. Each rating scale consisted of 20 specific informational items that were elicited through interviews with 60 cancer patients. The data were analyzed using percentages, means, Pearson correlation coefficients, t-test, and ANOVA. The results of this study were as follows; 1. Nurse subjects achieved a higher total score (85.6154) on the rating of importance than did the patients (81.5238) or the doctors (79.3125). The difference between the three group's total score was significant (F = 6.164, p less than .01) and the difference between the nurses' total score and doctors' was also statistically significant (t = 3.95, p less than .001). 2. On the whole, the rankings for the mean score of importance for the 20 items differed among the three groups of subjects. For the patient subjects, the highest mean ratings were for "the symptoms of recurring illness", "progress of illness", and "plan and duration of treatment" showing these to be the items that they considered important. The nurse subject felt that it was most important for oncology patients to know about "plan and duration of treatment", "how to minimize problems with loss of appetite, nausea, vomiting", and "amount of activity the patient can do around the work setting". Doctors felt it was most important for the patient to know about "prognosis of illness", "progress of illness", and "plan and duration of treatment". "Plan and duration of treatment" was the common item that all three groups perceived as important for patient learning.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2927072 TI - [Physiological changes of the elderly]. PMID- 2927071 TI - [A study on the relationship between pre- and post-hysterectomy sexual behavior differences and the sexual satisfaction of women who have had a hysterectomy]. AB - The objective of this study was to provide a basis for sexual counselling and education for women who have had a hysterectomy. This was a cross sectional descriptive correlation study. There were 230 subjects in the study. The time period from the hysterectomy varied from one month to eighteen months. The subjects were selected by a convenient sampling method. The tool for this study was developed by the researcher through a literature review, consultation from 36 women who have had a hysterectomy and nursing faculty. A pilot study was done to determine the necessary modifications. Data collection was done between Sept. 1987 and Dec. 1987 using a mailed questionnaire. The results of this study are summarized as follows; 1. The differences between pre-post hysterectomy sexual behavior in frequency was that all the sexual behaviors were decreased; the decreased rate of coitus was 20.7%, of kissing or embracing 10.9%, of fondling of sexual organs 8.7%, of female prone-position 3.3%, of petting 7.7%, of sexual day dream 1.0%. 2. For the low income group, the sexual behavior with the most significant decrease in frequency was fondling the sex organs (t = 2.21, p less than .05). For the housewife group, it was a decrease in the one of the female prone position (t = -2.02, p less than .05). For the group under the age of 39, it was petting (t = -2.13, p less than .05). The housewife group showed an increase in sexual day dreams as compared to the group having a job (t = -3.12, p less than .01). The group that did not received the post-op information, showed a significant decrease in kissing or embracing behavior (t = 2.73, p less than .01), and male prone position (t = -2.46, p less than .01), and also the group that did not receive the pre-op information showed a significant decrease of male prone position (t = -2.19, p less than .05), and also of petting (t = -2.95, p less than .01). 3. The relationship between sexual behavior pre-post hysterectomy differences and sexual satisfaction only showed a significant correlation for the sexual behavior of coitus (r = -2.012, p less than .001), and fondling of sex organs (r = -.1121, p less than .05). In conclusion, although there were a decrease in all sexual behavior after the hysterectomy, the difference between the pre hysterectomy sexual behavior and the post hysterectomy sexual behavior correlated with sexual satisfaction for only of the two behaviors. PMID- 2927073 TI - [The development of an occupational stress management tool for psychiatric nurses]. AB - The purpose of this study is to propose the baseline data for developing the occupational stress measurement tool for Psychiatric nurses Working in the hospital. 135 staff nurses in psychiatric unit of 11 hospital were participated during the period from August 1 to August 20, 1988. Though the pretest and literature review a questionnaire was constructed with 88 stressors which were experienced by the psychiatric nurses in the hospital. Subjects were given instruction to rate 1-6 likert type scale according to the level of stress experienced by each stressor described. Reliability of the tool was tested by Cronbach's Alpha and the result was alpha = 0.94871. Factor analysis was applied to organize 88 items together. As the result, 14 factors were obtained. The factors were; 1) Administration problem. 2) Work overload. 3) Role conflict as a profession. 4) Lack of professional knowledge and skill. 5) Conflict with nurses. 6) Conflict with other health teams. 7) Conflict in nurse-client relationship. 8) Conflict with supervisor. 9) Conflict with subordinate. 10) Low reward. 11) Scheduling problem. 12) Inappropriate physical environment. 13) Staff inadequate. 14) Inadequate of equipment. PMID- 2927075 TI - [Use of various methods of dialysis in intensive care patients]. PMID- 2927074 TI - [The nursing process]. PMID- 2927076 TI - [What are the possibilities of training asthmatics?]. PMID- 2927077 TI - Kinetics of cellular proliferation after arterial injury. V. Role of acute distension in the induction of smooth muscle proliferation. AB - Arteries denuded by the passage of a balloon catheter demonstrate marked smooth muscle cell (SMC) proliferation, whereas arteries denuded by a fine wire do not. We examined the possibility that vessel distension in addition to endothelial loss accounted for the SMC proliferation in the balloon model. Segments of rat left carotid isolated by temporary ligatures were distended hydrostatically with tissue culture medium at 300 mm Hg pressure via an external carotid cannula. Animals received either continuous [3H]thymidine infusion (intraperitoneally, Alzet pump, Alz Corp., Palo Alza, California) for 14 days or pulsed with [3H]thymidine at 1, 2, 3, or 7 days, and SMC proliferation was assessed by autoradiography. Distended vessels demonstrated patchy denudation acutely and complete endothelial regeneration by 3 days. No SMC were present in the intima at later times. Nevertheless, cumulative SMC proliferation over 14 days was 21 +/- 3% (perfused but not distended control: 0.8 +/- 0.6%; partially de endothelialized but not distended control: 0.3 +/- 0.1%). Pulse-labeling demonstrated a peak of SMC proliferation between 2 and 3 days after injury. These results suggest that acute distension can contribute to the induction of SMC proliferation after endothelial denudation. PMID- 2927078 TI - The induction of anagen hair growth in telogen mouse skin by cyclosporine A administration. AB - One clinical complication of immunosuppressive cyclosporine A (CsA) therapy is the stimulation of hair growth. Since few pharmacologic agents cause hypertrichosis, CsA appears particularly interesting for investigating the mechanisms which control normal hair formation. Previous investigators have shown that CsA affects the hair growth of the laboratory rat, several genetic variants of mice, as well as humans, and they have concluded that CsA influences keratinization predominantly. Using a well-defined in vivo assay which measures the induction of hair follicle growth, we report here that CsA induces resting (telogen) follicles to enter active growth (anagen) in normal laboratory mice (C57 B1-6), i.e., animals with a normal hair cycle. The experiments indicate that the rate of anagen induction is dependent on the dose, time course, and method of administration and that it may be mediated via a direct action of CsA on the skin and its appendages. These studies suggest that understanding the molecular mechanisms of CsA action on hair growth will help elucidate the mechanisms of normal anagen induction. PMID- 2927079 TI - Kinetics of excretion of 2-acetylaminofluorene in normal and xenobiotic-treated rats and in rats with hepatocyte nodules. AB - This study was designed to explore further the hypothesis that the special resistance phenotype seen in hepatocyte nodules during liver carcinogenesis could have a physiologic correlate in the manner with which a carcinogenic xenobiotic is handled. Hepatocyte nodules were induced in male rats by continuous or intermittent exposure to dietary 2-acetylaminofluorene over a 25-week period. Two or 5 weeks after the exposure, the animals were given a single dose of 9-14C-2 acetylaminofluorene. The amounts and rates of excretion of unconjugated compound and derivatives and of the glucuronic acid metabolites in the bile and urine and the amounts in the blood and liver were measured over a period of 180 minutes. For comparison, animals fed the basal diet alone, animals injected with phenobarbital or 3-methylcholanthrene, animals receiving a single dose of cobalt heme and animals fed the 2-acetylaminofluorene for only 2 weeks were studied. These groups were used as controls for different patterns of drug metabolism, especially relating to the cytochromes P-450. The nodule-bearing animals showed a pattern of handling of the carcinogen that is quite different than that of the animals of any other group. They excreted in the bile plus urine from 20 to 30% less. However, relatively much more was in the urine. The free and glucuronide conjugated metabolic products of the carcinogen were assessed by high performance liquid chromatography. The nodule-bearing animals and the animals treated with 3 methylcholanthrene excreted much more glucuronic acid esters. The pattern of distribution of labeled 2-acetylaminofluorene is different in the nodule-bearing rats than in other animals in which variations in phase I and phase II drug metabolizing enzymes were induced by treatment with cobalt heme, phenobarbital, 3 methylcholanthrene or short-term exposure to dietary 2-acetylaminofluorene. PMID- 2927080 TI - Kinetics of interaction of 2-acetylaminofluorene with normal liver and carcinogen induced hepatocyte nodules in vivo and in vitro. AB - This study examines the initial uptake and subcellular distribution of the carcinogen [14C]-2-acetylaminofluorene in liver nodules and normal liver. The route of administration of the carcinogen was intravenously through a peripheral branch of the superior mesenteric vein, intragastrically or intraperitoneally. Tissue distribution was initially dependent on blood flow, but the retention after 5 minutes varied between different tissues according to tissue affinity, high in liver, fat and muscle, low in kidney and brain. The major fraction was retained in the liver. In vitro experiments demonstrated that total levels of [14C]-2-acetylaminofluorene were 8-fold lower in hepatocytes from liver nodules compared with normal liver. The 2-acetylaminofluorene was bound more avidly to 12 to 15 kilodalton cytosolic proteins than to 40 to 50 kilodalton proteins in normal liver and this binding was much less in hepatocyte nodules. The subcellular distribution indicated that the microsomal fractions had a greater specificity than mitochondria, homogenate, or cytosol. This specificity was not due to the lipid content of the fractions. Microsomal fractions from liver nodules had 2-fold less [14C]-2-acetylaminofluorene bound than from normal liver. The carcinogen was bound in cytosolic proteins with a peak 90 minutes after intravenous injection, as compared with a peak for microsomes at 10 minutes. These results lend further support for the concept that the biochemical properties in liver nodules minimize the metabolism of xenobiotics in vivo. PMID- 2927081 TI - Specialized metaplastic columnar epithelium in Barrett's esophagus. A comparative transmission electron microscopic study. AB - Barrett's esophagus develops as a complication of regurgitant esophagitis and predisposes patients to the development of dysplasia and esophageal adenocarcinoma. Prior ultrastructural studies have suggested that Barrett's epithelium is a mucous secretory epithelium that shares some morphologic features with the intestine. The origin and development of Barrett's epithelium and the cellular abnormalities accompanying its neoplastic progression are poorly understood. In an attempt to better understand the histogenesis of the mucus producing cells that predominate in Barrett's epithelium, these cells were studied by transmission electron microscopy and compared with other upper gastrointestinal epithelia: esophageal glands, normal gastric surface, pit, and cardiac gland regions, gastric intestinal metaplasia, and normal jejunal villous tip and crypt regions. A total of 134 mucosal biopsies from the stomach and esophagus of 28 patients with Barrett's esophagus and 37 biopsies from 14 other control patients were studied. Barrett's specialized metaplastic surface cells display a spectrum of ultrastructural features among three main surface columnar epithelial cell types: mucous cells resembling those seen in the normal gastric surface epithelium or resembling mucous neck cells normally seen in the gastric pits; goblet cells similar to those seen in the jejunum; and "pseudoabsorptive" cells with features of both gastric mucous secretory cells and jejunal absorptive cells. Cytoplasmic organelles of Barrett's specialized metaplastic, normal gastric mucous neck, and normal gastric surface mucous epithelial cells, including rough endoplasmic reticulum, glycogen aggregates, Golgi apparatus, and mucous secretory granules, have common ultrastructural features associated with mucus synthesis. The morphologic heterogeneity of Barrett's specialized metaplastic cells and common ultrastructural features associated with normal mucus biosynthesis suggest that they develop from a gastrointestinal stem cell that retains the capacity for a wide range of normal and abnormal differentiation in the esophagus. The identity of this undifferentiated cell, which may reside in normal proximal gastric or esophageal mucosa, remains unknown. However, the gastric mucous neck cell has properties that suggest it could be the progenitor cell for Barrett's esophagus because it is a stem cell that has ultrastructural similarities to Barrett's specialized metaplastic epithelial cells and it is located in intact gastric mucosa adjacent to where Barrett's esophagus forms. PMID- 2927082 TI - Induction of glomerulosclerosis by dietary lipids. A functional and morphologic study in the rat. AB - Clinical and experimental data indicate that glomerular function and morphology may be influenced by plasma lipids. In familial lecithin-cholesterol acyltransferase (LCAT) deficiency and in Fabry's disease, lipids accumulate in glomeruli and are assumed to induce sclerosis. The present study was undertaken to examine if dietary lipids could exert effects on the glomeruli of normal, unilaterally nephrectomized rats, and of rats with two-kidney, one clip (2-K,1C) hypertension. In rats with two kidneys on a diet rich in fat and cholesterol, cholesterol concentrations in very low density lipoproteins increased. In these rats the number of glomeruli with sclerotic foci was significantly higher than in rats on a low fat, cholesterol free diet. After 6 months on the diet the percentage of glomeruli with sclerosis (SC) was 13.2 +/- 4.1 (N = 9) in rats with a cholesterol diet and 1.8 +/- 0.6 (N = 11) in control rats (p less than 0.05). The fat and cholesterol diet exacerbated glomerular lesions in the remnant kidney model of uninephrectomized rats. The sclerosis in rats with only one kidney was 38.2 +/- 9.5 (N = 6) on a cholesterol diet compared with 8.7 +/- 3.0 (N = 6) in control rats after 6 months (p less than 0.05). After 3 to 4 months on a fat rich diet cholesterylester was increased in isolated glomeruli. The composition of the dietary lipids influenced the development of glomerular lesions. A linseed oil diet that is rich in unsaturated fatty acids, especially linolenic acid, did not cause major plasma lipid abnormalities and was accompanied by a low sclerosis (1.2 +/- 0.3; N = 9) for rats with two kidneys. In rats with chronic 2-K, 1C hypertension the percentage of glomeruli with partially sclerosed tufts in the unclipped kidney was significantly higher on a fat and cholesterol diet (F) than on a control diet (N) (SC: diet F 31.0 +/- 4.0, N = 13; diet N 12.2 +/- 2.6, N = 12; P less than 0.05). In the clipped kidney, protected against the arterial hypertension, only an increased number of glomeruli with mesangial expansion was noted in rats with the cholesterol diet. Glomerular hemodynamic factors seem to play an important pathogenetic role in the induction of glomerular sclerosis by a lipid rich diet. The fact that dietary lipids can aggravate glomerular lesions in states of arterial hypertension and nephron loss may have implications for the progression of renal disease in humans. PMID- 2927083 TI - High density lipoprotein plasma fractions inhibit aortic fatty streaks in cholesterol-fed rabbits. AB - The effects of in vivo administration of high density lipoprotein-very high density lipoprotein (HDL-VHDL) on the development of aortic fatty streaks were studied in cholesterol-fed rabbits. The rabbits received a 0.5% cholesterol-rich diet for 8 weeks. During this period, the HDL-VHDL group was intravenously administered with 50 mg/week of homologous HDL-VHDL protein; the control group received normal saline (0.9% NaCl). HDL-VHDL fraction was obtained at density range 1.063 to 1.25 gm/ml by ultracentrifugation of normal rabbit plasma. Along the study, plasma lipid levels followed a similar profile in both groups. At the completion of the study, atherosclerotic-like lipid-rich lesions covered 37.9 +/- 6% (X +/- SEM) of the intimal aortic surface in the control group, and 14.9 +/- 2.1% in the treated group (p less than 0.001). The values of total and free cholesterol, esterified cholesterol, and phospholipids deposited within vessel wall were significantly lower in the aortas of the HDL-VHDL treated group than those in the control group. Cholesterol accumulation in the livers was also significantly lower (p less than 0.01) in the treated group than in the control. We concluded that administration of homologous HDL-VHDL lipoprotein fraction to cholesterol-fed rabbits, dramatically inhibited the extent of aortic fatty streaks and lowered lipid deposition in the arterial wall and liver without modification of the plasma lipid levels. PMID- 2927084 TI - Experimental arthropathy induced in rhesus monkeys and DBA/1 mice by a novel method: intraperitoneal implantation of type II collagen adsorbed onto nitrocellulose filters. AB - A novel method which avoids the use of complete Freund's adjuvant (which can be arthritogenic) has been used to induce collagen II arthritis in both primates and mice. A solution of bovine type II collagen was dried onto nitrocellulose filters and implanted in the peritoneal cavity of experimental animals. Primate and mouse joints were scored by clinical as well as gross and microscopic parameters. The polyarthritis that developed in both rhesus monkeys (Macaca mulatta) and DBA/1 LAC J mice was characterized by synovial cell proliferation and endothelial cell hyperplasia, and by a perivascular mononuclear cell infiltrate of the synovium. Primates were analyzed further for anti-type II collagen antibody titers and delayed type hypersensitivity to type II collagen. Anti-type II collagen serum titers appeared to be unrelated to the disease pathology; the primates did not display delayed-type hypersensitivity to type II collagen. Control monkeys and mice implanted with collagen-free nitrocellulose filters were normal upon clinical and histopathological analysis. This protocol offers the advantage of the induction of arthritis due solely to immunization with antigen. PMID- 2927085 TI - Preactive planning and conceptions of success in elementary health education. AB - Prospective classroom teachers' thoughts and understanding about teaching health were examined in this study. The study described the preactive thought processes of classroom teachers as they planned a lesson on health and teachers' conceptions of success and failure during the lesson. Before teaching a 30-minute lesson in health, participants were asked to "think aloud" during a planning session. Content of the thoughts was audiotaped, transcribed, and analyzed. After the lesson, participants listed critical events they described as related to success and lack of success during the lesson. Content of the written accounts was organized into clusters with common elements. Findings indicated teachers' concerns during planning were related to identifying and arranging content for maximum involvement and enjoyment. Most teachers defined success in terms of student affective rather than cognitive behaviors. PMID- 2927086 TI - Alcohol and drug abuse prevention in Wisconsin public schools. AB - This survey assessed the status of Wisconsin public school district programs designed to prevent alcohol and other drug related problems among students. The assessment involved surveying prevention program directors of 102 school districts that received grants for prevention initiatives since 1981. Most districts (70%) implemented programs at the elementary, middle, and senior high school levels. Typical program strategies involved combining information dissemination with refusal skill and self-concept development. School programs predominantly were school-based and did not systematically involve community members or agencies. The greatest obstacles to providing effective prevention services include high rates of alcohol and other drug use in homes and communities, denial of alcohol and other drug related problems among students, parents, and community members, and lack of staff time for prevention activities. Project directors indicated a need for schools to initiate greater involvement of parents, nonschool alcohol and drug abuse prevention agencies, and other community organizations in school efforts. PMID- 2927087 TI - The contribution of school health programs to the broader goals of public health: the American experience. PMID- 2927088 TI - Student alcohol use and perceived problems with peers and adults. AB - The authors examined the relationship between students' use of alcohol and the problems they experience with friends their own age and with four groups of adults, including the students' teachers or principal, police, parents or family, and adults in the neighborhood. Patterns among students' problems with friends and adults, and problems experienced by students who use alcohol, frequently get drunk, and frequently come to school drunk are explored. Using a stratified random cluster sample, 10,259 seventh through 12th grade North Carolina students were surveyed in spring 1987. For this study, the sample was limited to 6,526 students who reported drinking. No clear patterns emerged among the different groups of individuals with whom students could have problems, revealing a lack of coordinated intervention efforts among these groups. It was evident that teachers failed to detect and confront students who frequently come to school drunk. The need for increased intervention efforts is discussed. PMID- 2927089 TI - HIV education within comprehensive school health education: what does it mean? PMID- 2927090 TI - A small victory for Jamie Swartz. PMID- 2927091 TI - Establishing a system of complementary school-based surveys to annually assess HIV-related knowledge, beliefs, and behaviors among adolescents. AB - The Division of Adolescent and School Health, Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control has responsibility for assisting national, state, and local education agencies to provide effective HIV education for youth. In fall 1987, 14 state and 9 local education agencies that serve areas with the highest cumulative incidence of AIDS cases convened to develop a common set of data items that could provide comparable information about HIV-related knowledge, beliefs, and behaviors among adolescents in their respective jurisdictions over time. Surveys were administered during spring 1988 to representative samples of adolescents in each participating state and city. These education agencies will use the results from this complementary system of school-based surveys as a guide in planning HIV education, setting program priorities, allocating resources, and monitoring changes in HIV-related knowledge, beliefs, and behaviors among adolescents. PMID- 2927092 TI - Free condoms in the schools of Copenhagen, Denmark. AB - Attitudes of ninth grade students and their classroom teachers toward using condoms as a preventive measure against contracting AIDS were studied. Students (N = 438) and their teachers (N = 28) in the council schools of the Municipality of Copenhagen were surveyed using a structured questionnaire. Overall, results demonstrated that the message regarding "safe sex" had been well understood. However, 42% of pupils reported not using a condom during their last sexual intercourse. Many pupils indicated difficulty in using condoms. A continuing need exists for advice to the young. An information campaign, with distribution of free condoms, was well accepted by pupils and teachers. Almost all (94%) pupils indicated they will use condoms more frequently in the future. This campaign differed from other efforts that focused more on general information. The importance of other strategies designed to alter behavior to reduce the risk of contracting AIDS is discussed. PMID- 2927093 TI - The imperative for a national initiative in death-related phenomena. PMID- 2927094 TI - The Canada Youth and AIDS Study. PMID- 2927095 TI - Alignment of the first metatarsal-phalangeal joint: important criteria for a new joint replacement. AB - Joint replacement is one of many options for the treatment of the first metatarsophalangeal (MTP) joint. Studies of the geometry of that joint have shown that it consists of two distinct articulations, the metatarsophalangeal and the MT-sesamoidal. Both are important, but the MT-sesamoidal tolerates only small deviations from an ideal alignment. The aim of this study was to investigate the alignment of the first MTP joint of a potential patient population, in order to design an optimal surface replacement. One measurement, the extension angle between the MT and the proximal phalanx was found to be the most important alignment criterion for the successful design of an implant and the necessary instruments. This angle controls the delicate interplay between the metatarsal head and the sesamoids and tolerates only small deviations from the normal range before the chance of sesamoidal subluxation increases significantly. The pre operative knowledge of this and other alignment criteria is important for the ideal placement of an anatomical implant. PMID- 2927096 TI - Ultrastructural differences of the interface zone between bone and Ti 6Al 4V or commercially pure titanium. AB - Commercially pure (CP) titanium and Ti 6Al 4V alloy were sputtered onto polycarbonate plastic implants to analyse hard tissue reactions to the two metals. The implants were inserted in the tibial metaphyses of five rabbits. Three months later they were removed and processed for light microscopy (LM) and transmission electron microscopy (TEM) investigations. At the LM level, disordered woven bone was seen in the interface zone of Ti 6Al 4V, whereas organized bone was observed in direct contact with the CP titanium implants. TEM examination of Ti 6Al 4V sections revealed a 500-1000 A thick collagen-free proteoglycan layer compared to 200-400 A for CP titanium. A surface analysis test was performed to compare the magnetron sputtered film with bulk Ti 6Al 4V alloy. This test revealed no major differences between the experimental implant and the bulk alloy. More natural-like tissue reactions were observed to CP titanium than to Ti 6Al 4V alloy. PMID- 2927097 TI - Setting the baseline parameters for clinical assessment of foot to ground contact using the Musgrave pressure plate system. AB - The Musgrave Pressure Plate System for the measurement of foot contact patterns comprises two fixed pressure plates constructed from arrays of load cells, interfaced to a BBC computer. Its main advantage is the ability to measure and analyse spatial distributions of contact pressures and their time dynamics, and to do this relatively inexpensively in a clinical setting. Its main potential disadvantage is that it can disrupt the natural gait pattern by the discipline in enforces on the foot placement. The eventual aim of the project of which this study forms the pilot phase, is to develop formal decision rules based on the analysis of a large number of normal subjects for the diagnosis of abnormal foot pathology and the evaluation of therapy, using data collected by a Musgrave system. The objective of this study is to set baseline norms, and to evaluate the system. The analysis is based on 100 normal subjects using selected parameters on foot contact pressure, contact area and time, available from the system. Several stages of the foot contact process are described in terms of the selected parameters. The results show clearly that even with a relatively small subset of the available recorded data on each foot plant, a wide range of descriptive information can be accumulated. Statistically significant differences were found between the right and left feet on most of the parameters considered. However, these differences were based on a large sample and are not large in absolute terms in many instances. Therefore the observed differences may be small compared to differences between normal and abnormal cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2927098 TI - Pulsed Doppler ultrasound system for the measurement of velocity distributions and flow disturbances in arterial prostheses. AB - For the investigation of flow through prosthetic arteries a pulsed Doppler ultrasound system has been characterized. Preliminary in vitro experiments using this system are described; they verify its suitability for making velocity profile and flow disturbance measurements. The output from a frequency tracker is compared with spectral analysis of Doppler signals for both laminar and turbulent flow regimes and the root mean square fluctuations on the tracker output signal are used to identify transition from laminar to turbulent flow. In addition, the turbulent intensity of poststenotic flow is quantified at several axial locations and for different rates of flow. Finally, we present velocity profile measurements which were obtained using a deconvolution technique to account for the finite size of the sample volume. PMID- 2927100 TI - Evaluation of consistency among different electrical impedance indices of relative cerebral blood flow in normal resting individuals. AB - Significant correlation was observed, in normal resting individuals, of interregional variation of classical amplitude-dependent electrical impedance indices of cerebral blood flow (CBF) with three quantitative rheographic measures of cerebral blood flow which have been themselves radioisotopically validated. Since these amplitude-related CBF indices are derived from the Nyboer model relating blood volume changes to change of impedance, the data support the correctness and applicability of this model to the head. Interrelationship among the CBF parameters obtained with the use of this technique was found to be markedly affected by differing electrode placements; it was not apparently affected by extracranial circulation. It is concluded that under proper recording conditions, several assumptions underlying rheoencephalography are consistent and that it may be a useful tool for the study of relative regional cerebral blood flow in normal individuals. PMID- 2927101 TI - Spectral properties of signal averaging and a novel technique for improving the signal-to-noise ratio. AB - Averaging is one well-known method for improving the signal-to-noise (S/N) ratio of data or a time series, in which small amplitude responses to regularly occurring stimuli are contaminated by noise. We have considered the spectral properties of that process and introduce a new method which further improves the S/N ratio. We also demonstrate that the signal recovered by normal averaging is identical to that recovered by the frequency extraction technique which we propose. A formula for the sums-of-squares of the recovered signal is derived. The success of the frequency extraction technique has been demonstrated on sinusoids, white noise, evoked potentials contaminated by a background EEG, and the EEG recorded with the subject's eyes closed. PMID- 2927099 TI - Sensitivity analysis of the systemic circulation with a view to computer simulation and parameter estimation. AB - A sensitivity analysis study has been performed on a seven-parameter model of the systemic vascular bed in order to obtain structure reductions appropriate for simulation and estimation. This analysis considers separately the systolic and diastolic transfer functions between arterial and venous pressures in order to divide a non-linear problem in two distinct linear problems. The results obtained refer to nominal parameter values corresponding to normal circulatory conditions in man and supply guide-lines for an application-oriented selection of reduced models. Simple resistance-compliance models are preferred because the inertial effects appear to have only slight influence. In particular, the choice of a five parameter model seems to be convenient for simulation purposes. An additional structure reduction is suggested to reach reliable results in parameter estimation problems. The resulting model is characterized by three elements: peripheral resistance, arterial compliance and venous compliance. PMID- 2927102 TI - Spatial filtering in multichannel magnetoencephalography. AB - Partial differential equations in boundary-value problems have been studied in order to estimate the influence of several geometrical and physical parameters involved in the outward transmission of the brain's magnetic field. Explicit Green kernels are used to obtain integral forms of generalized solutions which can be deduced from each other, as expressed over concentric spherical surfaces. That leads to numerical applications dealing with the radial component of the magnetic field. From this study, a new spatial filtering is proposed as a possible improvement in two-dimensional magnetoencephalographic mapping using large multisensors. PMID- 2927103 TI - Presurgical finite element simulation of scoliosis correction. AB - For surgical correction of scoliotic spinal deformity, internal fixation systems apply lateral and distractive corrective forces. In order to gain maximal correction, a finite--element analysis of the spinal deformity correction technique has been carried out preoperatively, after first employing the spinal deformity correction finite--element model to determine the in vivo spinal stiffness. The presurgical analysis also gives us an appreciation of how the parameters of deformity, stiffness and corrective forces jointly contribute to the value of the correction index. The paper presents the methodology and clinical application. It also summarizes the results for ten patients, whereby the efficacy of presurgical analysis is assessed by comparing the corrective index values by presurgical simulation with the surgical results for equivalent levels of corrective forces. PMID- 2927104 TI - The value of the flow-volume loop in diagnosing upper airway obstruction. PMID- 2927105 TI - Community-acquired pneumonia and septic arthritis caused by penicillin-resistant pneumococci. PMID- 2927106 TI - Documented self-destruction. PMID- 2927107 TI - Blunt abdominal trauma associated with seat belt use. PMID- 2927109 TI - The solitary pulmonary nodule. PMID- 2927110 TI - Six ways to guarantee denial of your patient's Social Security disability benefits. PMID- 2927108 TI - Postsplenectomy sepsis syndrome. PMID- 2927111 TI - Prescription drug diversion: "what Lola wants, Lola gets". PMID- 2927112 TI - More on "bloody AIDS and AIDSy blood". PMID- 2927113 TI - Situs inversus with cholelithiasis: a case report. PMID- 2927114 TI - Dietary fluoride supplements for Tennessee's children: the role of the physician. AB - 1. All children should receive some form of systemic fluoride and appropriate forms of topical fluoride. 2. If a child is not receiving optimally fluoridated water, the physician or dentist should prescribe a dietary fluoride supplement as tablets or drops. 3. The correct dosage must be determined, based on patient age and fluoride content of the patient's drinking water. 4. Special attention is necessary concerning fluoride intake for children breast-feeding or consuming infant formula. 5. To arrive at the correct fluoride dose, these steps should be followed: (A) Whenever you do not have specific knowledge of water fluoride content, have a sample of the main drinking water source (usually home water) analyzed for the fluoride content before prescribing a fluoride supplement. (B) When the fluoride content of the water has been determined, the fluoride level and the child's age should be matched on Table 1 to arrive at the correct supplement dose. 6. The Fluoridation Program of the Tennessee Division of Water Supply can provide lists of communities and schools in Tennessee that are optimally fluoridated. PMID- 2927115 TI - Diagnosis and management of blunt pancreatic injury. PMID- 2927117 TI - Another cause of angina pectoris. PMID- 2927116 TI - Chronic fatigue and abdominal pain. PMID- 2927118 TI - Differences in drinking behavior among three Asian-American groups. AB - This article challenges the commonly held beliefs that there are few if any heavy drinkers among Asian-Americans and that different groups of Asians exhibit similar patterns of drinking. To explore these stereotypes, alcohol consumption patterns were compared in a survey of 298 Chinese, 295 Japanese and 280 Koreans in Los Angeles. Heavy drinking was found in each of the Asian groups. Gender specific logistic regression models were used to illustrate the differences in the drinking patterns of the Asian-American groups and to clarify the determinants of drinking. The greatest proportion of heavy drinking was found among the Japanese and the lowest among the Chinese. Having friends who drank was the only social factor consistently related to Asian drinking behavior. PMID- 2927119 TI - Impact of social desirability response sets on the self-report of marital adjustment in alcoholics. AB - The role of social desirability response sets on self-reported marital satisfaction in 143 male alcoholics and their wives was assessed in a factor analytic study of the combined Locke-Wallace Marital Adjustment Scale (MAS) and Edmonds Marital Conventionalization Scale (MCS). Overall, results indicated that alcoholics rated their marriage as significantly more satisfying than did their wives. There was, however, a large amount of covariation between the MAS and MCS for husbands, and factor analyses revealed considerable redundancy between the two measures as evidenced in one dominant factor on which both MAS and MCS items loaded. Although there was also high covariation between the two scales for wives, there was still enough differential responding to MAS and MCS items to identify both a dominant factor and a second factor, the latter loaded on only by MCS items. Results suggest that the self-reported marital satisfaction of male alcoholics may be highly contaminated by social desirability response sets. The results are discussed with respect to the two-component model of socially desirable responding and caution is urged in the evaluation of self-report marital adjustment measures with this population. PMID- 2927120 TI - Towards the assessment of adolescent problem drinking. AB - Longitudinal data were obtained from a nonclinical sample of 1,308 male and female adolescents covering the age range from 12 to 21. Factor analyses of 52 symptoms and/or consequences of alcohol use yielded three problem dimensions. In addition, a unidimensional, 23-item scale (the Rutgers Alcohol Problem Index, RAPI) was constructed with an internal consistency of .92. Correlations between RAPI and alcohol-use intensity were moderately strong for all age groups at each test occasion (ranging from .20 to .57), yet low enough to suggest that identification of problem drinkers requires both types of measures. The results suggest that the RAPI may be a useful tool for the standardized and efficient assessment of problem drinking during adolescence. PMID- 2927121 TI - Interactive effects of genotype and social environment on alcohol consumption in female twins. AB - Information about drinking practices has been obtained by questionnaire from 1,984 monozygotic and dizygotic adult female twin pairs from the Australian twin register, including 1,690 pairs where both twins have used alcohol. Statistical analyses of these data show that marital status is an important modifier of genetic effects on drinking habits. In young twins, aged 30 years or less, genetic differences between individuals account for only 31% of the variance in alcohol consumption of married respondents, but for 60% of the variance of unmarried respondents. In twin pairs, aged 31 years or more, genetic differences account for 46-59% of the variance in married twins, but for 76% of the variance in unmarried twins. In our young sample (average age 35 years) there is no evidence that individuals genetically predisposed to heavy drinking are any less likely to be married than the rest of the population. Some alternative explanations of these findings are also rejected. PMID- 2927122 TI - Identification of the alcoholic schizophrenic: use of clinical laboratory tests and the MAST. AB - A screening procedure to identify alcohol abuse among schizophrenics is sorely needed. We evaluated the utility of a particular screening battery that consisted of three standard clinical laboratory tests (GGTP, MCV, SGOT) and the Michigan Alcoholism Screening Test (MAST). Consecutive admissions to an acute psychiatric unit and to an alcohol rehabilitation program were initially evaluated for inclusion in three diagnostic groupings: alcoholic schizophrenics, nonalcoholic schizophrenics and nonschizophrenic alcoholics. Twenty inpatient veterans were selected for each diagnostic group. These groups were then compared in terms of scores on the GGTP, MCV, SGOT and MAST. The MAST had the greatest sensitivity, but suffered low specificity. The GGTP demonstrated excellent specificity, but very poor sensitivity. When multiple tests were considered, the combination of the MAST and GGTP proved the best at identifying alcohol abuse in schizophrenics. The false positive rate was unacceptably high, however. The test battery was not useful in discriminating between nonalcoholic schizophrenics and alcoholic schizophrenics, yet could distinguish the nonschizophrenic alcoholics from the two schizophrenic groups. PMID- 2927124 TI - Undergraduate student and faculty perceptions of problem drinking. AB - Using a questionnaire, 487 students and 155 faculty members at two midwestern undergraduate colleges were surveyed to learn the factors that affect perceptions of problem drinking. Multivariate analysis of variance showed perceptions to be significantly related to respondents' drinking habits. Multivariate analyses of covariance, with respondents' drinking as the covariate, revealed significant differences in perceptions between faculty and students and between male and female students. The gender of the questionnaire's target individual also affected perceptions. The results replicate and expand on findings explicating the role of demographic and cognitive factors in the perception of drinking. PMID- 2927123 TI - Public images of alcoholism: data from a Georgia survey. AB - Attitudes toward alcoholism among a representative sample of 524 adults in Georgia indicate acceptance of the disease concept remains incomplete. Despite expected regional differences, results from bivariate analyses are consistent with previous research conducted in other areas of the U.S. The Georgia data indicate similar levels of acceptance of the disease concept of alcoholism, similar demographic correlates with that acceptance and similar treatment recommendations for alcoholism. Attitudes toward alcoholism are found to be significantly correlated with views concerning cocaine dependence, but the acceptance of the disease concept of alcoholism is significantly greater. The multivariate discriminant analysis reveals that education and income are the most significant discriminators between the medical and moral/medical images of alcoholism, followed by religion, age and race. PMID- 2927125 TI - Reasons students give for limiting drinking: a factor analysis with implications for research and practice. AB - Dimensions of cognitions associated with self-regulation of alcohol consumption were studied using a 22-item Reasons for Limiting Drinking (RLD) scale in a student survey of nine universities. Data on 2,482 drinkers were factor analyzed using several methods in split halves and the total sample. Four interpretable factors accounting for 39% of the common variance were consistently found. Based on core content, these subjective motivational factors were labeled self-control, upbringing, self-reform and performance. Reliability analysis was used to construct subscales to assess these factors. Subscales had adequate internal reliability (alphas = .66-.73) for brief research scales. Relationships between the RLD subscales and between these subscales and selected demographic, alcohol consumption and problem indicators are summarized. Based on these results and an application in a prevention experiment with heavily drinking students, the niche for such "reasons" measures in participant screening and program evaluation is discussed. PMID- 2927126 TI - Alcohol abuse and familial alcoholism: psychosocial correlates in men and women. AB - Multivariate and univariate analyses were conducted to investigate specific hypotheses concerning the effects of alcohol abuse, family history of alcoholism and gender on items in five categories: (1) family of origin; (2) childhood attention deficit, conduct and learning disorders; (3) intraindividual (psychological) variables; (4) peers and family of procreation; and (5) sociocultural and community variables. The sample consisted of 76 male and 72 female detoxified alcoholics and 50 male and 51 female community controls. By selection procedures, groups had an approximately 50% incidence of familial alcoholism; all were given detailed structured interviews covering the above areas. Significant differences between alcoholics and controls were found for all five categories, and four of the five categories showed significant family history effects. Gender differences were present on only one category. There were no significant Alcoholism X FH interactions. We conclude that (1) alcoholism and family history of alcoholism are distinct, separate factors that have additive and not interactional effects; and (2) these separate effects seem to operate in similar fashion in both male and female populations. The findings have relevance for methodological considerations and the identification of problem areas of functioning in the adult alcoholic and nonalcoholic offspring of alcoholics. PMID- 2927127 TI - A path analysis of an adolescent drinking behavior model derived from problem behavior theory. AB - The interrelationships between composite variables comprised of demographics, socialization, personality, perceived environment, conventional and problem behaviors, and their combined mediational influences on adolescent drinking behavior are examined. Students randomly sampled from four suburban, metropolitan area high schools (N = 499) were administered the 250-question Survey of Underage Drinking Styles. All 12 composite variables, derived from the survey, were arranged in a causal model and submitted to a confirmatory path analysis. Data were analyzed by multiple regression procedures. According to the present model, a powerful pathway through to drinking may begin with family interaction problems, which may lead to a reduction in the adolescent's social coping skills. A reduction in the adolescent's coping skills may lead to a compensatory belief that alcohol improves mental and physical functions and an increased affiliation with and acceptance of the peer group's attitude and behavior toward consuming alcohol as a replacement coping skill. The adolescent's drinking may then increase as a result of the affiliative need to conform to peer group pressure. PMID- 2927128 TI - The effect of repeated occasions of alcohol intoxication on two processes involved in the visual discrimination of movement. AB - The focus of this study was the effect of repeated episodes of alcohol intoxication on two processes involved in visual movement discrimination: visual sensitivity and decision-making. Four female subjects were asked to discriminate between a stationary light signal and one that changed position in the center of a dark visual field. Prior to each of 15 alcohol testing sessions, a dose of .66 ml of 95% USP ethanol per kg body weight was administered to each subject and BAL was sampled frequently within sessions. Differences in subjects' pre- and postalcohol performance were evaluated within the framework of a psychophysical model that mathematically characterizes the problem of movement discrimination and yields independent estimates of visual sensitivity and decisional aspects of subjects' performance. Evidence for specificity in the development of sensory versus decisional process tolerance to intoxication effects was found. The major result was that each subject made large and statistically reliable shifts in decisional criteria during the time course of the blood alcohol curve within alcohol testing sessions, even when visual sensitivity had adapted to alcohol intake effects. The results of this study illustrate the utility of tracing acute intake effects over repeated occasions of intoxication, and empirically testing subjects' assumed decisional strategies when modeling these effects. PMID- 2927129 TI - Breath analysis and self-reports as measures of alcohol-related emergency room admissions. AB - This study reports breath-analyzer readings and self-reports as measures of alcohol-related admission to the emergency room of San Francisco General Hospital. A 20% probability sample of patients admitted during a 60-day period was breath analyzed and interviewed. Interviews and breath samples were obtained on 75% of the sample of 2,516 patients. Twice the proportion of injury patients compared to noninjury patients had positive admission breath samples and reported drinking prior to the event. Alcohol involvement reached 41% for self-reports among injured men and over half of both men and women injured in fights or assaults reported drinking prior to the event. Self-reported alcohol use was found to be a valid measure of alcohol consumption when compared to breath analyzer readings for the same individuals. Emergency room patients may be more likely than others to provide accurate reports of alcohol consumption if they feel that disclosure of amount and timing of drinking prior to an injury or illness could be important in their care. The data suggest that self-reports when used in conjunction with a quantifiable estimate of blood alcohol may be an appropriate method of ascertaining alcohol's involvement in emergency room cases. PMID- 2927131 TI - The Alcohol Dependence Scale: a validation study among inpatient alcoholics. AB - The present study investigated whether the degree of alcohol dependence, as operationalized by Skinner and Allen's Alcohol Dependence Scale (ADS), covaried with concurrent and predictive criteria in a sample of hospitalized alcoholics. As previously reported, the ADS was found to be unidimensional and internally consistent. However, compared to Skinner and Allen's findings, these inpatients had significantly lower ADS scores. Correlations with concurrent measures of cognitive functioning, psychiatric and physical symptoms tended to be smaller than, but in the same direction as, those previously reported using an outpatient sample. ADS scores did not significantly predict attrition from inpatient treatment, self-reported alcohol consumption over 9-month follow-up or duration of aftercare involvement. Patients who relapsed reported significantly higher ADS scores at admission, however, the magnitude of this relationship was modest (r = .16). In its present form, the ADS appears to have fair concurrent validity, but limited predictive utility within a sample of inpatient alcoholics. PMID- 2927130 TI - Long-term repeatability of human alcohol metabolism, sensitivity and acute tolerance. AB - Thirty-eight subjects in the Colorado Alcohol Research on Twins and Adoptees (CARTA) were brought back between 3 and 39 months after their initial testing to be retested on a shortened version of the standard CARTA procedures. As before, subjects were given a dose of ethanol (0.8 g/kg) calculated to bring their blood alcohol level (BAL) to near 100 mg/dl, but no topping doses were administered in the retests to maintain BALs near peak for 3 hours, as was done previously. Repeatability (test-retest correlation) for alcohol clearance rate was near zero, repeatability for time to peak BAL was 0.36 and that for peak BAL was 0.50. Repeatabilities of prealcohol baseline scores were generally high (median 0.55) for the shortened battery of physiological, motor coordination, perceptual speed and reaction time measures. Repeatabilities were near zero for sensitivity scores (median 0.02) and were low for acute tolerance scores (median 0.10) and perceived intoxication (median 0.27). These findings are highly consistent with an earlier report on repeatabilities of responses to alcohol over a 1-month time interval. PMID- 2927132 TI - Topographic distribution of EEG alpha activity during ethanol-induced intoxication in women. AB - Topographic maps of brain electrical activity from scalp EEG electrodes were obtained from healthy adult female volunteers using a Brain Electrical Activity Mapping (BEAM) system. Each woman received both ethanol (0.7 g/kg, p.o.) and placebo in a counterbalanced order under double-blind conditions at an interval of 1-6 days. Subjective reports of intoxication were obtained continuously via an instrumental joystick device. Subjects reported when they detected ethanol and qualitatively pleasant (i.e., euphoric) or unpleasant (i.e., dysphoric) effects. All subjects reliably discriminated ethanol from placebo. Pronounced increases in EEG alpha activity occurred during ethanol-induced intoxication in all subjects. Analysis of topographic maps revealed that the distribution of high-amplitude, fast-frequency EEG alpha activity extended further frontally to the central sulcus and temporally during ethanol intoxication than during control sessions or after placebo administration. Area analysis and significant probability mapping techniques were used to quantify the increased alpha activity and to monitor changes during the process of intoxication in each individual. One woman, with a positive family history of alcoholism, experienced only a mild degree of ethanol intoxication. This behavioral response was accompanied by a slight decrease or no change in both slow- and fast-frequency alpha activity. This finding in a single subject provides additional evidence that a possible genetic predisposition for ethanol-related effects on behavior may be reflected in measures of brain electrical activity. Overall, these data also suggest that ethanol induces rapid and widespread increases in EEG alpha activity which may be associated with the reinforcing properties of ethanol. PMID- 2927133 TI - Nutritional effects of postgastrectomy reconstruction: a clinical evaluation. AB - To evaluate the nutritional benefits of a jejunal pouch vs. esophagojejunostomy following total gastrectomy, we reviewed 24 consecutive cases of total gastrectomy: 14 males and 10 females, 39 to 85 years of age (mean 66.6 y.) undergoing 9 jejunal pouches (JP) and 15 Roux-en-Y esophagojejunostomy (EJ). Indications for surgery included 15 adenocarcinomas, 3 lymphomas, 1 leiomyoma, and 5 hemorrhagic gastritis. The operative mortality was 12.5%. One JP patient was lost to follow-up. The mean survival for EJ was 13.3 months and for JP 36 months. Total gastrectomy resulted in persistent weight loss and hypoalbuminemia, and the creation of a jejunal pouch did not seem to improve significantly the nutritional status following total gastrectomy. PMID- 2927134 TI - Incidence and anatomic distribution of cutaneous melanoma among United States Hispanics. AB - Using the data base for melanoma incidence compiled by the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute, we compared the incidence and anatomic distribution of primary cutaneous melanomas in Hispanic and non-Hispanic Caucasian populations and in blacks between 1973 and 1981. Cases were divided into United States whites, New Mexico (NM) whites (non Hispanic Caucasians), NM Hispanics, Puerto Rico (PR) residents by definition Hispanic, and US blacks. Among whites, the highest incidence was 8.0 per 100,000 and was ten times that of US blacks. The incidence among PR and NM Hispanic residents was 1.6 to 3.7 times that of US blacks. The anatomic distribution among NM Hispanics was similar to US and NM whites for both genders. In contrast, among PR residents the anatomic distribution in both genders was most common for the leg, similar to that for blacks. Spaniards who migrated to PR have more admixture with blacks from Africa than Spaniards who migrated to the mainland. This suggests a genetic predilection for the occurrence of melanoma on the lower extremity among PR residents as opposed to NM Hispanics. PMID- 2927135 TI - Prostate cancer in blacks: an update from the American College of Surgeons' patterns of care studies. AB - Data from the American College of Surgeons' prostate cancer surveys covering nearly a decade of experience demonstrate that the problem of prostate cancer is unique among black men in the United States. These data show that the distribution of stage at diagnosis changed across the 10-year interval. The data indicate that there have been improvements in the 5-year survival rates of both black and white patients, but the prostate cancer-specific survival of black patients remains significantly poorer than that of whites. PMID- 2927136 TI - Optimal debulking following chemotherapy of advanced-stage epithelial ovarian carcinoma. AB - We reviewed the records of 110 consecutive patients with advanced-stage epithelial ovarian carcinoma treated at the Soroka Medical Center, Beer-Sheva, Israel, from 1961-1987. Twenty patients (18.1%) had optimal debulking at initial laparotomy, 30 patients (27.2%) had nonoptimal debulking at initial laparotomy, 20 patients (18.1%) had an "inoperable" disease at initial laparotomy, and 40 patients (36.3%) had such poorly written records that no information about the degree of resectability at initial laparotomy could be obtained. Four patients, in whom the residual tumor left at initial laparotomy had responded to chemotherapy, had a second laparotomy. In all four patients optimal debulking surgery at second laparotomy was easy to perform and was successful. The value of a second laparotomy after a few cycles of chemotherapy in order to optimally debulk the residual tumor left at initial laparotomy is discussed. It is concluded that a second attempt of debulking surgery after chemotherapy has a respectable place in the management of patients with advanced-state epithelial ovarian carcinoma, but further research is needed. PMID- 2927137 TI - Determinants of survival in patients with unresectable colorectal liver metastases. AB - Prognostic indicators in 67 patients with unresectable colorectal liver metastases were analyzed. These patients were identified to have isolated hepatic metastases after extensive radiological evaluation and demonstrated good performance status without evidence of liver failure. Univariate analysis revealed 6 of 22 factors that were associated with survival: alkaline phosphatase (AP), lactic dehydrogenase (LDH), occult intra-abdominal extrahepatic disease, percent hepatic replacement by tumor (PHR), sex, and carcinoembryonic antigen (CEA). A multivariate analysis identified two independent factors that jointly influenced survival: AP and PHR. Patients with an AP greater than 175 U/liter had a greater than threefold relative risk of dying compared with patients with AP less than or equal to 175 U/liter (P = 0.0001). Patients with PHR II or III (25 75%, greater than 75%) also had a greater than threefold relative risk of dying compared with patients with PHR 1 (less than 25%; P = 0.0074). Our patient population is typical of that being entered into trials examining experimental therapies. Alkaline phosphatase and extent of liver involvement by tumor are significant prognostic indicators that should be accounted for in such studies. PMID- 2927138 TI - Bilateral radical neck dissection: report of results in 55 patients. AB - Between 1952 and 1982, 55 patients underwent bilateral radical neck dissections at the National Cancer Institute. Of these, 17 patients had simultaneous (one stage) bilateral dissections and 38 had nonsimultaneous (two-stage) dissections. In 37 patients both internal jugular veins were removed, while one vein was preserved in 18 patients. The operative mortality was 11.8% (2/17 patients) for simultaneous bilateral neck dissections and 2.6% (1/38 patients) for nonsimultaneous staged dissections. The overall operative mortality was 5.4%. Of the 18 patients in whom one jugular vein was preserved, six patients (33%) had postoperative facial edema and swelling, while of the 37 patients in which neither jugular vein was saved, 20 patients (54%) developed significant postoperative facial edema. The overall 2-year recurrence rate was 50%. The overall survival rates were 55% at 3 years and 39% at 5 years. PMID- 2927139 TI - Invasion and metastasis following orthotopic transplantation of human pancreatic cancer in the nude mouse. AB - A good experimental model for metastasis of human pancreatic cancer would be a valuable tool for the study of this process, which contributes significantly to morbidity and mortality. Models of experimental metastasis using injection of tumor cells into the portal or systemic circulation bypass some important steps of the metastatic process. We describe invasion and metastasis following orthotopic transplantation of human pancreatic carcinoma into nude mice. Tumor pieces were used as xenografts in this study, and metastases were observed in the regional lymph nodes, liver, lungs, and distant lymph nodes of the animals. Peritoneal implants and ascites were not observed in this study. Orthotopic transplantation of human pancreatic cancer in the nude mouse appears to be a promising model of spontaneous metastasis relevant to clinical reality. PMID- 2927140 TI - Lung resection for metastatic sarcomas: total survival from primary treatment. AB - The results of surgical management of 63 cases of pulmonary metastases from bone and soft tissue sarcomas, admitted at the Istituto Nazionale Tumori of Milan, between 1970 and 1987, are reviewed in this paper. To estimate the relative impact of metastasectomy on the overall performance of treatment, survival curves were calculated from the time of first thoracotomy, as well as from the initial treatment of primary sarcoma. In the present series, total actuarial survival at 10 years was 37% for osteosarcoma, 27% for soft tissue sarcomas, and 24% for the other bone sarcomas, with a median survival of 48, 56, and 36 months, respectively. Five-year survival from the first pulmonary resection was influenced by the number of metastases and the length of the first disease-free interval only in osteosarcoma, while in soft tissue sarcomas a major untoward factor was represented by local recurrence at the site of the primary tumor. These data support the concept of pulmonary metastasectomy as effective salvage therapy for radically treated sarcomas; this management can rescue a significant proportion of all relapsed patients. PMID- 2927141 TI - Factitious microcalcifications in breast biopsy material: laboratory-induced error by use of tattoo powder for specimen mammography. AB - A xeromammogram led to the surgical excision of a calcified breast lesion on a 66 year-old female. Before specimen mammography was performed, the excised tissue was oriented with tattoo pigment. The specimen mammogram then revealed multiple calcifications caused by unsuspected radio-opaque material in the tattoo pigment, and the original calcifications were obscured. This case demonstrates the hazards involved utilizing tattoo powders for orienting xeromammographically discovered specimens. PMID- 2927142 TI - Inflammatory pseudotumor of the liver. AB - Inflammatory pseudotumors (plasma cell granulomas) are localized lesions consisting of a fibrous stroma, chronic inflammatory infiltrate with a predominance of plasma cells, and an absence of anaplasia, which can mimic malignant disease by their gross appearance. Reported in many sites, they are most frequently described in the lung. Twelve cases involving the liver and biliary tract have previously been reported. Here, a 77-year-old man who presented with fever and malaise was found to have a lesion in the left lobe of the liver, which, on exploration, was found to be an inflammatory pseudotumor. This patient, and each of those previously reported, has recovered uneventfully. Because of the benign course of this lesion, hepatectomy should be considered only in those instances in which the mass effect of the lesion is producing symptoms or in those cases in which a firm histologic diagnosis cannot be made preoperatively or by frozen section intraoperatively. PMID- 2927143 TI - 18th annual UCLA symposium. Abstracts: Biotechnology and human genetic predisposition to disease. PMID- 2927144 TI - 18th annual UCLA symposium. Abstracts: Plant gene transfer. PMID- 2927145 TI - 18th annual UCLA symposium. Abstracts: Molecular mechanisms in DNA replication and recombination. PMID- 2927146 TI - 18th annual UCLA symposium. Abstracts: Molecular and cellular biology of yeasts and filamentous fungi. PMID- 2927147 TI - 18th annual UCLA symposium. Abstracts: Molecular biology of the cardiovascular system. PMID- 2927148 TI - 18th annual UCLA symposium. Abstracts: Obesity: towards a molecular approach. PMID- 2927150 TI - 18th annual UCLA symposium. Abstracts: The polymerase chain reaction: methodology and applications. PMID- 2927149 TI - 18th annual UCLA symposium. Abstracts: Structural and organizational aspects of metabolic regulation. PMID- 2927151 TI - 18th annual UCLA symposium. Abstracts: Parasites: molecular biology, drug and vaccine design. PMID- 2927152 TI - Tough new child support legislation. PMID- 2927153 TI - Empowerment of the staff nurse: a means to an end and an end in itself. PMID- 2927154 TI - Nursing practice cabinet. Update on practice guidelines on withdrawing or withholding food and fluids from patients. PMID- 2927155 TI - Health, welfare & government affairs cabinet. PMID- 2927156 TI - Carcinoma of the lung. Evaluation of satellite nodules as a factor influencing prognosis after resection. AB - Satellite nodules are considered to be predictive of poor prognosis in breast cancer and in melanoma. In lung cancer, there is no information as to their definition, prevalence, or implication as a prognosis factor of survival after resection. Over the past 18 years (1969 to 1987), 84 patients underwent pulmonary resection for primary lung cancer accompanied by satellite nodules. These nodules were defined as well-circumscribed accessory carcinoma foci clearly separated from the main tumor but with identical histologic characteristics. All were smaller than the primary carcinoma and most were located within the same lobe. Survival rates of patients with satellite nodules were compared to those of 1021 patients without satellite nodules who underwent resection during the same time interval. The 1-, 3-, and 5-year survival rates for all patients classified as having no satellite nodules were 78%, 54%, and 44%, respectively, and the median survival for the entire group was 30 months. In patients with satellite nodules, these survival rates were 60.9%, 32.7%, and 21.6%, respectively, with a median survival of 15 months. The deleterious effect of satellite nodules was more significant in patients with stage I disease (p = 0.0008) than in patients with stage II (p = 0.0354) or stage III (p = 0.0145) disease. Survival data obtained by comparison of satellite nodule status and histologic characteristics shows that 5-year survival figures are better for patients with no satellite nodules in both the squamous and the nonsquamous groups. This study demonstrates that satellite nodules associated with lung cancer are indicative of locally advanced and/or premetastatic disease. These patients should be included in the stage group IIIa of the TNM stage grouping classification. PMID- 2927157 TI - Physiologic role of the mitral apparatus in left ventricular regional mechanics, contraction synergy, and global systolic performance. AB - In animal models, severing the chordae tendineae of the mitral valve reduces the maximum global left ventricular elastance (Emax,g), a load-independent measure of left ventricular systolic performance; moreover, chamber geometry is altered with systolic bulging in the region of the papillary muscle insertions. This suggests that forces transmitted by the mitral apparatus increase the regional volume elastance (Emax,r) of segments subtending the insertions of the papillary muscles, and these regions contribute substantially to overall left ventricular systolic function (Emax,g). To test this hypothesis, we developed a method to evaluate changes in the magnitude and uniformity of Emax,r as quantitated by the slopes (E'max,i) of regional left ventricular isovolumetric pressure-dimension relations. Such measurements were obtained before and after all chordal attachments of the mitral valve were surgically divided in seven open-chest swine preparations. Significant declines in E'max,i were limited to the region of the posteromedial papillary muscle insertion. Although the mean E'max,i of all ventricular regions (E'max,ave) was unchanged, regional left ventricular elastances were less uniform after the mitral chordae tendineae were severed, which indicated a less synergistic contraction, and Emax,g fell by 21% from 7.1 +/- 2.0 to 5.6 +/- 1.2 mm Hg/ml (p less than 0.05). These data demonstrate that the mitral apparatus contributes importantly to the magnitude and uniformity of regional left ventricular elastances and suggest that such alterations in regional mechanics underlie the deterioration in global left ventricular systolic performance (Emax,g) after excision of the mitral apparatus. PMID- 2927158 TI - Does open lung biopsy affect treatment in patients with diffuse pulmonary infiltrates? AB - The decision to perform open lung biopsy in the evaluation of a diffuse pulmonary infiltrate is based on the probability that this examination will yield specific information that may lead to a change in treatment. The role of this procedure remains controversial and many clinicians are reluctant to allow this invasive procedure without assurances that results will lead to a change in therapy for a significant number. To evaluate the impact of open lung biopsy on diagnosis and treatment of diffuse pulmonary infiltrates, we conducted a retrospective review of 61 patients undergoing this procedure at three university-affiliated hospitals during a recent 7-year period. There were 37 men and 24 women; average age was 57 years. Biopsy yielded a specific diagnosis in 21 (34%) patients and a change in therapy in 33 (54%) patients. A complication developed in 11 (18%) patients, directly related to the biopsy procedure in six (10%). Eight patients died. The immune status in 22 (36%) patients was compromised. A specific diagnosis was obtained in 13 (59%) immunocompromised patients and a change in therapy occurred in 17 (77%) of these patients after biopsy. A specific diagnosis was obtained in only eight (21%) of the 39 noncompromised patients and therapy was changed in 16 (41%) patients in this group (p less than 0.02 compromised versus noncompromised). Morbidity and mortality were not significantly different between the two groups. A nonspecific diagnosis led to a change in therapy as frequently as a specific diagnosis in both compromised and noncompromised groups. Open lung biopsy in the patient with a diffuse pulmonary infiltrate is an accurate diagnostic tool and frequently leads to a change in patient treatment. The procedure can be performed with acceptable morbidity and mortality in immunocompromised and noncompromised patients. PMID- 2927159 TI - The effect of age on cerebral blood flow during hypothermic cardiopulmonary bypass. AB - Cerebral blood flow was measured in 20 patients by xenon 133 clearance methodology during nonpulsatile hypothermic cardiopulmonary bypass to determine the effect of age on regional cerebral blood flow during these conditions. Measurements of cerebral blood flow at varying perfusion pressures were made in patients arbitrarily divided into two age groups at nearly identical nasopharyngeal temperature, hematocrit value, and carbon dioxide tension and with equal cardiopulmonary bypass flows of 1.6 L/min/m2. The range of mean arterial pressure was 30 to 110 mm Hg for group I (less than or equal to 50 years of age) and 20 to 90 mm Hg for group II (greater than or equal to 65 years of age). There was no significant difference (p = 0.32) between the mean arterial pressure in group I (54 +/- 28 mm Hg) and that in group II (43 +/- 21 mm Hg). The range of cerebral blood flow was 14.8 to 29.2 ml/100 gm/min for group I and 13.8 to 37.5 ml/100 gm/min for group II. There was no significant difference (p = 0.37) between the mean cerebral blood flow in group I (21.5 +/- 4.6 ml/100 gm/min) and group II (24.3 +/- 8.1 ml/100 gm/min). There was a poor correlation between mean arterial pressure and cerebral blood flow in both groups: group I, r = 0.16 (p = 0.67); group II, r = 0.5 (p = 0.12). In 12 patients, a second cerebral blood flow measurements was taken to determine the effect of mean arterial pressure on cerebral blood flow in the individual patient. Changes in mean arterial pressure did not correlate with changes in cerebral blood flow (p less than 0.90). We conclude that age does not alter cerebral blood flow and that cerebral blood flow autoregulation is preserved in elderly patients during nonpulsatile hypothermic cardiopulmonary bypass. PMID- 2927161 TI - New technique for analysis of cardiac energetics using a modified Fenn equation. AB - In 12 dogs being supported by cardiopulmonary bypass, the relationship among myocardial oxygen consumption and four energy-consuming factors (basal metabolism, heart rate, tension development, and external work) was studied. Tension (internal work) in the left ventricular wall was evaluated by myocardial tissue pressure with a Mikro-Tip pressure transducer. In an empty beating heart with constant perfusion pressure, both systolic tissue pressure and developed tissue pressure represented the same characteristics as developed tension measured by other methods. As the heart rate was increased, the systolic tissue pressure and developed tissue pressure continued to increase stepwise (Bowditch effect) up to some stimulation rate, at which, however, a decrease began despite a further increase in heart rate (Woodworth effect). Significant regression was established between myocardial oxygen consumption and heart rate, tension (developed tissue pressure x heart rate), and external work (minute work): myocardial oxygen consumption = (9.05 x 10(-3) heart rate) + (1.95 x 10(-4) developed tissue pressure) x heart rate + (1.63 x 10(-3) minute work) + 1.42 (r = 0.7999), where activation energy = 9.05 x 10(-3) ml/100 gm per beat, tension related energy = 1.95 x 10(-4) ml/100 gm per unit of internal work, energy for work = 1.63 ml/100 gm per unit of external work, and basal metabolism = 1.42 ml/min/100 gm. We concluded that myocardial tissue pressure is a good substitute for tension and that multiple regression with heart rate, tension, and external work (as by modified Fenn's equation) seems indispensable to predict myocardial oxygen tension in the whole heart. PMID- 2927160 TI - Preloading history influences pressure-volume-derived indices of myocardial contractility in the ejecting canine left ventricle. AB - The dependency of indices of myocardial contractility on the immediate preloading protocol was assessed in 14 pentobarbital anesthetized open-chest dogs. An intracavitary micromanometer and epicardially placed ultrasonic dimension transducers allowed acquisition of dynamic left ventricular pressure-volume relationships while varying preload on right heart bypass. A resting cardiac output of 75 ml/kg/min was either increased twofold or reduced to zero flow over a 20-second interval. Linear regression analysis of the mechanical parameters permitted construction of the end-systolic pressure-volume relationship, rate of pressure rise-end-diastolic volume relationship, and the preload recruitable stroke work relationship. The slopes of the end-systolic pressure-volume relationship and rate of pressure rate-end-diastolic volume relationship were significantly higher when measured during volume depletion than during volume expansion (17.2 +/- 1.3 versus 8.5 +/- 0.8 mm Hg/ml and 205 +/- 14 versus 126 +/- 11 mm Hg/sec/ml, p less than 0.001, respectively). This finding was also evident when data analysis was confined to the initial 10 seconds of the loading interval. Nonlinear regression analysis of pooled data from both preloading protocols revealed curvilinear characteristics for each relationship. In contrast, the slope of the preload recruitable stroke work relationship was lower as a result of volume unloading (16.8 +/- 2.0 versus 22.8 +/- 1.7 mJ/beat/100 gm left ventricle/ml, p less than 0.01) and was independent of loading protocol when data analysis was confined to the initial 10-second acquisition period. Furthermore, second-order regression analysis of the pooled data showed no curvilinearity. These findings emphasize the importance of both the timing and method of varying cardiac preload in the determination of intrinsic myocardial contractility and suggest that the preload recruitable stroke work relationship may be a more linear contractile index that is less affected by preloading history over brief intervals. PMID- 2927162 TI - Treatment of esophageal achalasia (cardiospasm) with diaphragmatic graft. Twenty five years' experience. AB - Long-term results are presented in 60 patients (4 to 50 years old) who underwent a diaphragmatic graft procedure for relief of cardiospasm (achalasia) from 1962 through 1987. The operative technique involves construction of a pedicle flap of diaphragm. The muscular defect on the lower segment of the esophagus and the transplanted diaphragmatic pedicle that is sutured to the defect must be the same size. Immediate operative results were good. Only one complication developed, a case of pneumonia that was cured. The patients were followed up from 11 months to 25 years. Two patients were lost to follow-up, 55 had excellent results, and three patients still had nausea and heartburn but were better than before the operation. This procedure has three advantages: (1) It prevents the development of fistulas and diverticula at the site of the esophageal muscular defect; (2) it effectively eliminates both restenosis resulting from scar tissue and reflux esophagitis; and (3) it allows the cardia to recover its normal function and the esophagus to return to normal size at the site of the operation. PMID- 2927163 TI - Sensitivity of the recently infarcted heart to cardioplegic arrest. Beneficial effect of pretreatment with orotic acid. AB - The mortality and morbidity of cardiac operations are increased in the presence of an established, recent myocardial infarct. To help understand the mechanisms for this and to develop a therapeutic strategy, we studied the response of the recently infarcted canine heart to hypothermic cardioplegia and the effect of pretreatment with orotic acid. Orotic acid is a precursor of nucleic acids with the ability to enhance protein synthesis. In 21 greyhound dogs, a myocardial infarct was produced by ligation of the left anterior descending coronary artery. Ten of these then received oral orotic acid (100 mg/kg/day) for 4 days and 11 were untreated. A sham group of eight dogs had a thoracotomy only and therefore had normal hearts (normal group). Four days later, all dogs underwent 60 minutes of cardioplegic arrest at 28 degrees C. Before arrest, stroke work index was lower and myocardial oxygen consumption at comparable work levels was higher in both the orotic acid and untreated infarct groups than in the normal group. After arrest and reperfusion, there was a severe depression of ventricular function in the untreated infarct group, with only 18% recovery of prearrest stroke work. In the orotic acid infarct group, recovery of prearrest function (43%) was similar to that in the normal group (56%) and significantly greater than in the untreated infarct group (p less than 0.01). After reperfusion, the untreated infarct group had a lower oxygen consumption, lower myocardial levels of adenosine triphosphate and glycogen, and higher lactate and water contents than before arrest (all p less than 0.05). In the orotic acid and normal groups, these variables returned to prearrest levels. We conclude that an established, recent myocardial infarct places the noninfarcted myocardium under stress and increases its sensitivity to hypothermic cardioplegia. This sensitivity is markedly reduced by treatment with orotic acid. PMID- 2927164 TI - Studies of retrograde cardioplegia. I. Capillary blood flow distribution to myocardium supplied by open and occluded arteries. AB - This study defines the nutritive (i.e., capillary) distribution of blood cardioplegic solutions delivered via retrograde and antegrade techniques to muscle supplied by open and occluded coronary arteries where myocardial segments are in jeopardy of inadequate cardioplegic protection. Open-chest anesthetized dogs were studied by mixing radioactive microspheres (15 +/- 5 microns) with a blood cardioplegic solution and administering cardioplegia either into the coronary sinus or into the proximal aorta with the left anterior descending coronary artery open or occluded (30% +/- 2% area at risk). Nutritive flow (i.e., percentage of delivered 15 microns microspheres trapped in myocardial capillaries) during retrograde infusions averaged 65% versus 87% with antegrade cardioplegia (p less than 0.05). Retrograde and antegrade cardioplegic nutritive flow to all left ventricular regions was comparable with the left anterior descending coronary artery open (65 versus 82 ml/100 gm/min, p greater than 0.05), and both methods provided preferential hyperperfusion of subendocardial muscle (endocardial/epicardial ratios 1.6 and 1.5, respectively). Nutritive flow to muscle supplied by the occluded left anterior descending coronary artery was preserved better by retrograde than antegrade cardioplegia (35 versus 5 ml/100 gm/min, p less than 0.05). Preferential subendocardial hyperperfusion was maintained during retrograde cardioplegia (52 ml/100 gm/min, endocardial/epicardial ratio 1.6), but flow was redistributed away from subendocardial muscle with antegrade cardioplegia (less than 2 ml/100 gm/min, endocardial/epicardial, 0.29, p less than 0.05). Left ventricular flow was reduced markedly during retrograde infusion with the left anterior descending coronary artery open or occluded (23 and 12 ml/100 gm/min), but septal cooling was superior to antegrade cardioplegia (15 degrees +/- 1 degree C versus 20% +/- 3%, p less than 0.05) despite near-normal antegrade septal flow (the left anterior descending coronary artery was ligated beyond the first septal branch). Right ventricular nutritive flow was only 7 ml/100 gm/min during retrograde coronary sinus perfusion and was maintained normally with antegrade cardioplegia.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2927165 TI - Studies of retrograde cardioplegia. II. Advantages of antegrade/retrograde cardioplegia to optimize distribution in jeopardized myocardium. AB - This study tests the hypothesis that retrograde/antegrade cardioplegic delivery can overcome the limitations of poor cardioplegic distribution resulting from either technique alone and, potentially, may expand the safety of using internal mammary artery grafts in cardiac muscle in jeopardy of inadequate cardioplegic protection. Jeopardized myocardium was produced in 20 dogs by ligating the left anterior descending coronary artery for 15 minutes before starting cardiopulmonary bypass and by 1 hour of aortic clamping with multidose 6 degrees C cold blood cardioplegia. Five dogs received antegrade cardioplegia via the aortic root. Ten dogs received retrograde cardioplegia via the coronary sinus. Five additional dogs received retrograde/antegrade cardioplegia via both routes. The ligature on the left anterior descending coronary artery was removed after aortic unclamping, and regional myocardial temperature (thermistor probe), segmental shortening (ultrasonic crystals), and global left ventricular and right ventricular myocardial function were evaluated. Antegrade cardioplegia produced excellent right ventricular cooling (14 degrees C) and allowed complete right ventricular functional recovery. However, it failed to cool muscle supplied by the left anterior descending coronary artery (only 31 degrees versus 12 degrees C, p less than 0.05), postischemic global left ventricular function recovered only 38% (p less than 0.05), and segmental shortening in the region supplied by the left anterior descending coronary artery recovered only 22% (p less than 0.05). Retrograde cardioplegia produced homogeneous cooling (17 degrees C) and allowed near normal recovery of global and regional left ventricular function (99% and 86%), but right ventricular cooling was variable (19 degrees to 30 degrees C) and right ventricular function recovered inconstantly (range 64% to 100%, average 82%). The best myocardial protection occurred after retrograde/antegrade cardioplegia; myocardial cooling was homogeneous, left ventricular and right ventricular global function recovered completely (95% and 90%), and regional contractility in muscle supplied by the left anterior descending coronary artery returned to 84% of control. We conclude that retrograde/antegrade cardioplegia provides better myocardial protection than either technique alone, ensures good cardioplegic distribution to the left and right ventricles, and allows regional delivery of cardioplegic flow to segments supplied by occluded arteries.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2927166 TI - Direct lymphatic drainage of lung segments to the mediastinal nodes. An anatomic study on 260 adults. AB - The subpleural lymphatics of 483 lung segments were injected in cadavers of 260 adult subjects. The injected lymph vessels corresponded to the pulmonary segmentation in 91% of the cases and remained close by in the other cases. Direct passages to the mediastinal nodes were observed in 54 of 243 right lung segments injected (22.2%) and 60 of 240 left lung segments (25%). Among a total of 114 direct passages observed, 99 remained superficial in the pleura, half of them composed of a single vessel. These passages have been observed more frequently in the segments of the upper lobes. Injections of basal segments in the right and left lower lobes showed fewer of these direct passages to the mediastinal lymph nodes and also demonstrated direct lymph vessels to lymph nodes located at the origin of the upper lobar bronchi. In two dissections of the right upper lobe, the drainage went directly to the right venous jugular-subclavian junction, and in three dissections from three right terminal basal segments the lymph vessel went directly to the thoracic duct in its mediastinal passage. Direct contralateral lymph pathways were observed five times, four of them from basal segments of lower lobes. PMID- 2927167 TI - A versatile retractor for use in harvesting the internal mammary artery and performing standard cardiac operations. AB - A versatile retractor is described that can be used to harvest either mammary artery without disturbing the operative field and can be converted to a standard sternotomy retractor. It uses the principle of elevating the cut sternal edge and applying external pressure to the area of the costochrondal junction to rotate the mammary pedicle into view. We have used this retractor and found it to be very efficient in exposing the mammary pedicle while being atraumatic to the sternum. PMID- 2927168 TI - Total cavopulmonary connection. PMID- 2927169 TI - Resolution of intracardiac masses. PMID- 2927170 TI - Esophageal perforation. PMID- 2927171 TI - Repair of ascending aortic dissection. PMID- 2927172 TI - Echinococcal disease of both lungs and liver: successful simultaneous resection. PMID- 2927173 TI - Medium pH determines the differentiation of human promyelocytic leukemia cells to basophils or eosinophils by culturing in a protein- and serum-free medium. AB - Cells containing large basophilic granules in the cytoplasm appeared after culturing human promyelocytic leukemia cells (HL-60) in a protein- and serum-free alkaline medium. These granules were stained with toluidine blue and alcian blue. Cells were morphologically and cytochemically similar to basophils. The existence of histamine in the cell lysates was detected in both uninduced and alkaline medium-induced HL-60 cells. After culturing HL-60 cells in a protein- and serum free acidic medium, cells containing eosin-stained small granules (eosinophils) appeared. The differentiation of HL-60 cells to basophils or eosinophils may therefore depend on medium pH by culturing in a protein- and serum-free medium. PMID- 2927174 TI - Diagnostic significance of dysplastic features of peripheral blood polymorphs in myelodysplastic syndromes. AB - Dysplastic features of peripheral blood granulocytes were studied to investigate the diagnostic value estimating cytoplasmatic hypogranulation and nuclear abnormalities of the pelgeroid type in myelodysplastic syndromes (MDS). Hypogranulation was measure both as the percentage of agranular neutrophils and as a score value, taking into account also cells with slight or moderate hypogranulation. We studied 62 cases of MDS (18 refractory anemia, 11 sideroblastic anemia, 26 refractory anemia with excess of blasts, three chronic myelomonocytic leukemias, four refractory anemia with excess of blasts in transformation). For comparison we studied 13 cases of myeloproliferative disorders, 18 patients with different forms of anemia and 20 normal controls. Reference values were defined as the 95% probability limit of the mean values of normal controls. In MDS 52/62 patients (84%) had increased numbers of pelgeroid cells, 40/62 (65%) had abnormal granulation scores while only 14/62 (23%) had increased percentages of agranular neutrophils. The mean granulation score (+/- S.D.) in MDS (225.0 +/- 57.4), was significantly lower (p less than 0.001) than in myeloproliferative disorders (282.7 +/- 9.0), anemias (288.8 +/- 8.0) and normal controls (281.7 +/- 12.9). Pelgeroid neutrophils were significantly (p less than 0.001) more common in MDS (11.6% +/- 7.8) compared to myeloproliferative disorders (1.1% +/- 1.0), anemias (3.1% +/- 2.0) and normal controls (1.9% +/- 1.5). There was no significant correlation between the degree of hypogranulation and the percentages of pelgeroid cells in individual patients. Hypogranulation tended to be more pronounced in the more immature forms of MDS while pelgeroid cells were equally common in the different subgroups. When the two parameters were combined peripheral blood dysplasia was recognized in 92% of the MDS cases. The results suggest that quantitative estimation of hypogranulation and of nuclear abnormalities in peripheral blood polymorphs are simple and valuable diagnostic tools in MDS. PMID- 2927175 TI - Increasing the accumulation of daunorubicin in human leukemic cells by prolonging the infusion time. AB - Eight patients with acute nonlymphoblastic leukemia were treated with a combination of daunorubicin (1.5 mg/kg body weight) and cytosine arabinoside. The infusion time of daunorubicin was varied from 10 min to 24 h. One patient received the drug during 24 h in one treatment course and during 10 min in the subsequent course. The concentrations of daunorubicin and its main metabolite, daunorubicinol, were monitored simultaneously in plasma and in leukemic cells using high performance liquid chromatography. Infusion during 24 h gave a peak plasma concentration of daunorubicin that was less than one tenth of that observed after infusion for 10 min, while the areas under the plasma concentration vs time curves were similar. In contrast, prolonging the infusion time increased the area under the cellular concentration vs time curve from a mean of 3.3 nmol x h/mg cell protein for infusions less than one hour to 13.7 and 17.0 nmol x h/mg cell protein in two patients who received the same dose as a 24 h infusion. The duration of the infusion did not influence the intracellular levels of daunorubicinol. We conclude that the infusion times appear to affect the concentration of daunorubicin in the leukemic cells and may be important for the therapeutic effects of daunorubicin. PMID- 2927176 TI - Prediction of survival during induction therapy in patients with newly diagnosed acute myeloblastic leukemia. AB - Among 569 patients with newly diagnosed AML, 16% died in the 4 weeks following initiation of remission induction therapy. Eight pretreatment characteristics were found to be independently associated with 4-week survival: performance status, bilirubin, age, neutrophil count, fibrinogen, albumin, hemoglobin, and creatinine. A model incorporating these characteristics prospectively stratified a separate group of 198 patients into two comparably sized groups differing substantially in both 4-week survival rates (71% (95% confidence limits, 61-80%) vs. 91% (95% confidence limits, 83-96%] and in survival rates throughout remission induction. Characteristics associated with failure to survive 4 weeks were unassociated with resistance to therapy. This suggests that patients who fail to survive induction are qualitatively different than patients who survive induction but exhibit resistance to treatment. Different therapeutic strategies might be appropriate in the two groups. The model presented here can be used to identify patients at increased risk of death during remission induction. PMID- 2927177 TI - Antigenic variations of retrovirus in Japanese cancer patients. AB - Previously we demonstrated the prevalence of human T lymphotropic virus type I (HTVL-I) infection among cancer patients in Japan. This study was carried out to examine antigenic properties of retroviruses prevalent among Japanese cancer patients. Sera of 126 Japanese patients with cancer of different organs and with no history of blood transfusion, 94 in adult T cell leukemia (ATL)-endemic area and 32 in ATL-nonendemic area, were surveyed for antibodies to HTLV-I and HTLV-II by enzyme-linked immunosorbent assay (ELISA), Western blot analysis, and indirect immunogold electron microscopy. Among patients who were seropositive to HTLV-I, 39 of 56 (69.6%) in ATL-endemic area and 9 of 9 (100%) in ATL-nonendemic area were seropositive also to HTLV-II. Of 48 sera positive to both HTLV-I and HTLV II, 34 (70.8%) showed stronger reactivities to HTLV-I than to HTLV-II. Among patients who were seronegative to HTLV-I, 3 of 38 (7.9%) in ATL-endemic area and 5 of 23 (21.7%) in ATL-nonendemic area were seropositive to HTLV-II. Antibodies appearing and disappearing in sera of patients examined during the clinical course reacted with peptide species of HTLV-I and/or HTLV-II not always consistent with peptide species cross-reactive between HTLV-I and HTLV-II. These results indicate the antigenic diversity of retroviruses prevalent among Japanese cancer patients. PMID- 2927178 TI - Childhood acute promyelocytic leukemia: a rare variant of nonlymphoid leukemia with distinctive clinical and biologic features. AB - Of 251 consecutive cases of childhood acute nonlymphocytic leukemia (ANLL) seen at St. Jude Children's Research Hospital over a 12-year period, 16 (6.4%) were classified as promyelocytic according to the French-American-British definition. Patients with this form of leukemia were older at diagnosis than the group representing all other ANLL subtypes (median age, 14.8 vs. 9.0 years); they had lower leukocyte counts (median, 4.5 vs. 25.9 x 10(9)/liter), and a higher percentage were girls (68% vs. 44%). They also were much more likely to have a coagulation abnormality (75% vs. 13%). Only 44% of the promyelocytic group achieved complete remission, compared with 79% of the remaining patients (p = 0.001); however, after a median follow-up of 3.5 years, all but two of the responding patients with promyelocytic leukemia remain in complete remission. The majority of induction failures in the promyelocytic group (six of nine) resulted from complications that developed during periods of marrow hypoplasia or before hypoplasia was induced; whereas in the comparison group, more than half of the patients who failed had evidence of absolute or relative drug resistance. It is concluded that acute promyelocytic leukemia in children differs sufficiently from other subtypes of childhood ANLL to justify clinical trials of selective therapy. Recommendations for the use of heparin and blood component support in these patients are given. PMID- 2927179 TI - Cytogenetic heterogeneity in erythroleukemia defined as M6 by the French-American British (FAB) Cooperative Group criteria. AB - Chromosomal banding studies were performed on 10 patients diagnosed as having the M6 subtype of acute nonlymphocytic leukemia (erythroleukemia) according to the French-American-British (FAB) Cooperative Group criteria revised in 1985. Five patients had complex karyotypic abnormalities consisting of three or more defects, four of the five had deletion 7q, and three of the four had monosomy 5 or deletion 5q; the other five patients had normal karyotype. The patients of the former group had significantly higher white blood cell and blast cell counts in the peripheral blood and a higher serum lactate dehydrogenase level than the patients of the latter group. The progress of the disease in the former group was aggressive, resulting in a very poor prognosis. In contrast, the patients in the latter group had a relatively stable clinical course, resulting in a significantly longer survival. Furthermore, erythroblasts of all the patients with normal karyotype were negative or at most weakly positive to periodic acid Schiff reaction, whereas the cells were strongly positive in three of five patients with complex defects. Accordingly, we suggest that M6 subtype is cytogenetically heterogeneous, and that chromosomal findings are a useful prognostic indicator of this disorder. PMID- 2927180 TI - Acute myeloblastic leukemia with t(8;21) following Philadelphia positive acute lymphoblastic leukemia. AB - A patient with Philadelphia positive (Ph'+) acute lymphoblastic leukemia (ALL), in remission for over 4 years, developed an acute myeloblastic leukemia (AML), M2 type. During the second disease, the blast cells displayed a typical t(8;21)(q22;q22) translocation, in the absence of the Ph' chromosome. This is the first observation in the same patient of two leukemias displaying different cell phenotypes and each associated to one of the most characteristic chromosome changes. Cytogenetic characteristics and clinical aspects of the diseases are suggestive for the occurrence of two independent leukemic processes. PMID- 2927181 TI - Abrogation of the biological activity of the CFU-S inhibitor AcSDKP by a polyclonal antiserum. PMID- 2927182 TI - Can we increase the cure rate of adults with acute lymphoblastic leukemia? PMID- 2927183 TI - Expected utility theory and risky choices with health outcomes. AB - Studies of people's attitude towards risk in the health sector often involve a comparison of the desirability of alternative medical treatments. Since the outcome of a medical treatment cannot be known with certainty, patients and physicians must make a choice that involves risk. Each medical treatment may be characterized as a gamble (or risky option) with a set of outcomes and associated probabilities. Expected utility theory (EUT) is the standard method to predict people's choices under uncertainty. The author presents the results of a survey that suggests people are very risk averse towards gambles involving health related outcomes. The survey also indicates that there is significant variability in the risk attitudes across individuals for any given gamble and that there is significant variability in the risk attitudes of a given individual across gambles. The variability of risk attitudes of a given individual suggests that risk attitudes are not absolute but are functions of the parameters in the gamble. PMID- 2927184 TI - Measurement of the discomfort component of illness. AB - Discomfort is a prominent component of illness, but it is difficult to measure on a scale that allows its formal inclusion in a health status index. The authors tested the content validity of defining various discomforts in terms of their quality, duration, and intensity and found no responses that could not be categorized within this conceptual framework. They then analyzed the ability of patients to ascribe preference values to a sample of discomfort statements, based on this characterization of discomfort, and found them able to do this reliably using magnitude estimation. These results show that, although the universe of discomforts cannot be measured directly on a common scale, they can be compared using a scale of social preference. This will allow the formal incorporation of the discomfort component of illness into health status indexes based upon dysfunctions, discomforts, and prognosis. PMID- 2927185 TI - The treatment of patients with asthma by specialists and generalists. AB - The authors investigated possible differences between specialists and generalists in the intensity with which they treat patients with asthma by studying the care of 283 patients between the ages of six and 40 provided by 13 allergists and 40 randomly selected physicians in two primary care specialties: pediatrics and family practice. After excluding patients with more than one physician, allergists' patients were nearly identical to primary care physicians' patients in the frequency and duration of symptoms, and they had a similar number of asthma-related emergency room visits in the previous year and asthma-related hospitalizations in the preceding 3 years. The allergists treated their patients significantly more intensively than did the primary care physicians. Sixty-two percent of allergists' patients had received oral corticosteroids in the preceding year compared with 30% of primary care patients (P less than 0.001). More of the allergists' patients had received oral corticosteroids throughout the year (9% vs. 0%, respectively, P less than 0.01). They were also more likely to have used corticosteroid inhalers (46% vs. 19%) and a greater number of asthma medications (mean = 2.8 vs. 1.3). In a separate survey of the same physicians, using clinical vignettes, the allergists were more likely to prescribe corticosteroid tablets and inhalers. These findings suggest that specialists and generalists differ in the intensity with which they treat patients with asthma and cannot be explained by patient selection or severity differences. PMID- 2927186 TI - [Health care services in Canada: public financing has a monopoly but there is also a competition among health care providers]. PMID- 2927187 TI - [Dyslexia--a forgotten handicap]. PMID- 2927188 TI - [The question of cholesterol: the cholesterol value is not a suitable indicator of risk of myocardial infarction and early death in women]. PMID- 2927189 TI - [A lack of disagreement in the debate on psychopharmacology in team psychiatry]. PMID- 2927190 TI - [Concentration aimed at the screening of high-risk HPV carriers]. PMID- 2927191 TI - [The frequency of hepatitis B in Malmo is not influenced by a program of replacing the injection needles of drug addicts]. PMID- 2927192 TI - [Screening of cancer in ulcerative colitis--unnecessary surgery should be avoided]. PMID- 2927193 TI - [A course on pediatric allergology in Reykjavik: the biggest problem is underdiagnosis and undertreatment of asthmatic symptoms]. PMID- 2927194 TI - [Thrombosis of the superior vena cava caused by catheterization. Successfully treated with streptokinase]. PMID- 2927195 TI - [Prevention of ventricular fibrillation after long RR intervals using a pacemaker]. PMID- 2927196 TI - [Erroneous diagnosis of ventricular tachycardia--dangerous but unnecessary?]. PMID- 2927197 TI - [Magnetic resonance for better possibilities in studying the connection between alcohol and brain damage]. PMID- 2927198 TI - [Surgery in the very old--an analysis of patients over the age of 85 at a department of general surgery]. PMID- 2927199 TI - [Recommendations from an expert meeting on the prevention and treatment of osteoporosis]. PMID- 2927200 TI - [Risk of liver reactions after treatment with flucloxacillin]. PMID- 2927201 TI - [News from abroad. Fatal cases of overdose of triazolam (Halcion)]. PMID- 2927202 TI - [Ethical guidelines in transplantation. The right of self-determination is decisive for organ donation. Agreement is to be assumed when patients have not stated otherwise]. PMID- 2927203 TI - [An active marketing of research results makes research more useful for society]. PMID- 2927204 TI - [Sexual abuse of children and adolescents]. PMID- 2927205 TI - [Amalgam poisoning--unproved and uncertain]. PMID- 2927206 TI - [Better treatment of changes in the vocal cords when phoniatrists and microsurgeons cooperate]. PMID- 2927207 TI - [Benefits of bronchoscopy in hemoptysis and normal pulmonary X-rays in patients over 40 years of age]. AB - Opinion has been divided as to the benefit of bronchoscopy in cases of haemoptysis but normal chest radiograms. In this study such patients were compared with a reference group of haemoptysis patients with X-ray changes. Of the former group 44 underwent bronchoscopy, but after a follow-up of 57 months malignancy has been found in only one case, as compared with a malignancy rate of 47 per cent in the reference group. Thus it is concluded that bronchoscopy is to be recommended in cases of haemoptysis and X-ray changes, whereas non-invasive investigation should suffice in patients under 40 years of age and without X-ray changes, though the risk of malignancy increases with age, particularly in smokers and ex-smokers. PMID- 2927208 TI - [Regulation of the supply of nerve growth factor results in good development of neural graft]. PMID- 2927209 TI - [Vaccines today and tomorrow]. PMID- 2927210 TI - [Thalassemia can cause microcytic, therapy-resistant anemia]. PMID- 2927211 TI - [Sexual abuse of children and adolescents--a review based on somatic symptoms]. PMID- 2927212 TI - Otologic manifestations of AIDS: the otosyphilis connection. AB - Five cases of otosyphilis presenting in patients with HIV infection are discussed. The group is representative of the known stages of the disease, from asymptomatic carrier to the fully expressed immunodeficiency syndrome, and it is of relevance because otosyphilis appears to have developed at an accelerated rate from the primary infection. Four patients had been treated with penicillin 2 to 5 years previously and had a positive fluorescent treponemal antibody absorption (FTA-ABS) test. The fifth had concurrent neurosyphilis and was VDRL-test (Venereal Disease Research Laboratory) negative 2 years prior to the onset of symptoms. In all five patients, syphilis was in the latent stage. It is proposed that it is during this phase of the disease that HIV may alter its course and hasten the development of otosyphilis. It is also suggested that otosyphilis can present at any stage of HIV infection and should be considered in seropositive patients presenting with otologic complaints. PMID- 2927213 TI - The early signs and symptoms of neurotologic complications of chronic suppurative otitis media. AB - The delay in the diagnosis of neurotologic complications of chronic suppurative otitis media has been explained in a number of ways, including antibiotic suppression, surgical drainage, and a lowered index of clinical suspicion because the problem is relatively rare today. Twelve cases of neurotologic complications of chronic suppurative otitis media were reviewed to determine the early and late findings that should raise the physician's index of suspicion. Purulent, malodorous drainage, headache, and fever were the significant early findings. Altered mental status was a late finding, and usually indicated established intracranial infection. By drawing attention to the early findings, we hope to lower the morbidity and mortality associated with these complications. PMID- 2927214 TI - Evaluation of syncope from head and neck cancer. AB - Five patients suffering from recurrent syncope in association with metastatic squamous cell carcinoma of the head and neck were examined. Two patients had exhaustive diagnostic work-up for syncope, which eventually disclosed previously undiagnosed, recurrent squamous cell carcinoma. Case reports describe glossopharyngeal neuralgia, a well recognized cause of syncope in the head and neck cancer patient, characterized by acute unilateral head or neck pain preceding each syncopal episode. The literature on the diagnosis of syncope is reviewed, and the syncopal mechanisms unique to the head and neck cancer patient are analyzed and discussed. A diagnostic approach to syncope in head and neck cancer is proposed. PMID- 2927215 TI - Epiglottitis in AIDS patients. AB - Adult epiglottitis in patients with acquired immunodeficiency syndrome has not been previously reported. A pale, floppy epiglottis with supraglottic edema, cervical lymphadenopathy, a normal to low white blood count without a shift to the left, and rapidly progressive airway obstruction characterize this entity. In this small series of patients, conservative medical management was not successful, and aggressive airway intervention with appropriate intravenous antibiotic therapy was necessary. PMID- 2927217 TI - Middle fossa acoustic tumor surgery: results in 106 cases. AB - Although the middle cranial fossa approach has been used less frequently in recent years than in the past, it continues to be a useful technique for the removal of small acoustic tumors with possible hearing preservation. The approach provides complete exposure of the contents of the internal auditory canal, thus allowing positive facial nerve identification and facilitating total tumor removal. This paper reports the results of 106 middle fossa acoustic tumor removals over a 25-year period. Measurable postoperative hearing remained in 59% of cases. In 89% of cases, normal or near-normal postoperative facial nerve function was obtained. Total tumor removal was achieved in 98% of cases. Preoperative selection criteria are discussed, and postoperative complications are reported. PMID- 2927216 TI - The shelf life of the University of Pennsylvania Smell Identification Test (UPSIT). AB - The shelf life of the University of Pennsylvania Smell Identification Test was studied by comparing, using a within-subjects design, scores for tests manufactured within 2 months of the time of testing, 2 1/2 years before the time of testing, and 4 years before testing. A three-way analysis of variance (test age by gender by booklet presentation order) revealed no significant effects of test age, presentation order, or any of the interactions on the average test scores. However, a significant gender main effect was observed (the women outperformed the men). The number of persons who correctly identified each test item was examined using the Cochran Q test. A significant difference was found among the three groups for only one of the 40 items (lemon). The percentage of persons who correctly identified lemon was lowest with the 4-year-old tests (respective percentages of correct values for the recent, 2 1/2-year, and 4-year tests were 100%, 97%, and 67%). It is not clear, however, whether this variation is the result of test age, per se, or vagaries in the manufacturing process. Overall, the data indicate that tests stored in a dry place at room temperature have a long shelf life and can be validly used for assessing patient smell function. PMID- 2927218 TI - Laryngeal foreign bodies in children: a persistent, life-threatening problem. AB - We reviewed the records of all patients admitted to Cardinal Glennon Children's Hospital for foreign object aspiration from 1980 to 1987. There were 11 true glottic bodies, which accounted for 12.1% of the 91 foreign bodies detected in the airways. A mortality rate of 45% (5 patients) and transient hypoxic encephalopathy in 27% (3 patients) indicate the often tragic outcome of obstruction in the pediatric larynx. Two distinct types of foreign bodies were responsible for laryngeal obstruction in these children. The first group consisted of bulky items, mostly food, and resulted in a more severe type of obstruction, with higher mortality and morbidity. The second group of objects were thin, laminar, triangular bodies, which tended to wedge unsuspectedly in the larynx, mimicking inflammatory diseases and requiring endoscopy for their removal. Hypothetical models are used to explain the physical phenomena that occur in foreign body obstruction in the two different groups. Recommendations for intervention are made based on the conclusions. PMID- 2927219 TI - Bioinhibition of human fibroblast cultures sensitized to Q-switch II dye and treated with the Nd: YAG laser: a new technique of photodynamic therapy with lasers. AB - Kodak Q-switch II dye has recently proven to be an effective biostimulative agent on normal human fibroblast cultures. The potential for this dye as a new chemosensitizing agent for the treatment of connective tissue diseases and wound healing with the Nd:YAG laser was examined. Two normal fibroblast cell lines were first sensitized to a nontoxic dose of Q-switch II dye, then subjected to treatment with an Nd:YAG laser at 1,060 nm, with varying levels of energy and temperatures determined by a reproducible method of dosimetry. The results indicate that Q-switch II dye at nontoxic doses of 0.1 micrograms/ml enhances the cytotoxic effects of the Nd:YAG laser at temperatures as low as 36 degrees C. Furthermore, at physiological temperature ranges as low as 24 degrees C to 34 degrees C, cell duplication was inhibited, but cell viability was not affected. Similar results were not observed when fibroblast cultures were treated with the laser alone. These observations suggest that Q-switch II dye is an effective chemosensitizing agent for the Nd:YAG laser and could potentially be used to reduce collagen deposits in conditions such as keloids and hypertrophic scars. PMID- 2927220 TI - Practical computer applications for a head and neck cancer registry. PMID- 2927221 TI - Forehead flap nasal reconstruction with tissue expansion and delayed pedicle separation. PMID- 2927222 TI - Fiberoptic identification of the obscured trachea. PMID- 2927224 TI - Airway maintenance after bronchoscopy. PMID- 2927223 TI - The correction of cryptotia with a new prosthesis using the invaginating force produced by the deformity. PMID- 2927225 TI - Effects of exposure time and pulse parameters on CO2 laser osteotomies. AB - Two sets of experimental linear osteotomies were performed on frozen cortical bone by means of a high-power industrial CO2 laser in the rapid superpulsed mode, varying the velocity of the operating table, the mean power of the laser beam, the pulsewidth, the pulse repetition rate, and the peak power. Both the depth and the width of the osteotomies were inversely related to the velocity and directly related to the mean power and to the pulsewidth, but they were not affected by changes in the repetition rate. The depth/width ratio, which describes the profile of the osteotomies, was affected by the mean power only. These data permit greater accuracy in the planning of laser osteotomies in cortical bone when using the rapid super-pulsed mode. PMID- 2927226 TI - Anastomosis of bypass grafts using a low-powered CO2 laser. AB - The purpose of this study was to evaluate the feasibility of using a low-powered CO2 laser to perform end-to-side anastomoses of bypass grafts. The internal jugular veins of 13 domestic swine were removed and used as grafts to bypass their ligated carotid arteries. Each end of the vein graft was apposed to the artery with four to six temporary stay sutures, and a waveguide delivery CO2 laser with a power density of 900 mW/mm2 was used to perform the anastomoses, after which the sutures were removed. The animals were sacrificed postoperatively at five time intervals: 2 to 4 hours, 5 days, 1 month, 3 months, and 5 months. Of the 10 anastomoses studied at 2 to 4 hours, 70% were fully patent, none thrombosed, and 30% disrupted. Of the 16 anastomoses studied between 5 days and 5 months postoperatively, 88% were patent, 12% thrombosed, and none disrupted. None of the animals developed aneurysms at any stage of this investigation. Histologic analysis of acute studies revealed thermal damage such as charring of tissue, unraveling of the collagen fibrils, and the formation of microvacuoles. Within 3 months, the anastomotic sites showed localized healing with intimal fibromuscular proliferation and dense fibrous tissue. Good apposition of tissue was found to be of great importance in achieving patency of vessels in this procedure. PMID- 2927227 TI - In vitro optical properties of human and canine brain and urinary bladder tissues at 633 nm. AB - Absorption and scattering coefficients and scattering anisotropy factor are presented for human and canine cadaver tissues at the helium-neon wavelength (633 nm). Measurements were performed with an integrating sphere arrangement and analyzed with the diffusion approximation of the equation of radiative transfer adapted to Kubelka-Munk techniques. PMID- 2927228 TI - Laser-assisted vasovasostomy. AB - To find a less time-consuming alternative to conventional microsurgical vasovasostomy, we performed vasal anastomosis in four sterilized men by means of a Nd:YAG laser (wavelength 1,060 nm) under macroscopic conditions. After dissection of the vasal ends, the ends were approximated using 6-0 prolene sutures as intervasal stents. The apposed tissue edges were welded by laser pulses of 0.5 sec in duration and 10 W in power. Postoperative sperm counts proved normal in two patients; one of them reported a successful pregnancy in his wife 12 months after vasovasostomy. One patient had cryptospermia and one patient oligoasthenospermia. Laser-assisted vasovasostomy is a simple procedure and shortens the operative time. More patients still need to be studied to allow a favorable comparison with conventional suture techniques. PMID- 2927229 TI - Hazard zones and eye protection requirements for a frosted surgical probe used with an Nd:YAG laser. AB - Detailed radiometric analyses are reported on selected frosted-style laser surgical probes that are in use in laser surgical procedures. These measurements were performed in order to determine their nominal hazard zone (NHZ) and the requirement for protective eyewear. All measurements were conducted under worst case conditions using a 30-W Nd:YAG laser. The results show that for the style of probe tested, the NHZ can be considered a spherical volume of 1.3 m and will require eye protection devices having a maximum optical density rating of 4.3 at 1.06 microns for all personnel who may come within that range. PMID- 2927230 TI - Effect of helium-neon and infrared laser irradiation on wound healing in rabbits. AB - We examined the biostimulating effects of helium-neon laser radiation (HeNe; 632.8 nm), pulsed infrared laser radiation (IR; 904 nm), and the two combined on skin wound healing in New Zealand white rabbits. Seventy-two rabbits received either 1) no exposure, 2) 1.65 J/cm2 HeNe, 3) 8.25 J/cm2 pulsed IR, or 4) both HeNe and IR together to one of two dorsal full-thickness skin wounds, daily, for 21 days. Wound areas were measured photographically at periodic intervals. Tissue samples were analyzed for tensile strength, and histology was done to measure epidermal thickness and cross-sectional collagen area. Significant differences were found in the tensile strength of all laser-treated groups (both the irradiated and nonirradiated lesion) compared to group 1. No differences were found in the rate of wound healing or collagen area. Epidermal growth was greater in the HeNe-lased area compared to unexposed tissue, but the difference was not significant. Thus, laser irradiation at 632.8 nm and 904 nm alone or in combination increased tensile strength during wound healing and may have released tissue factors into the systemic circulation that increased tensile strength on the opposite side as well. PMID- 2927231 TI - Effect of low-energy laser irradiation on colony formation capability in different human tumor cells in vitro. AB - Fibroblasts and lymphocytes are the most widely used cells for studying the so called biostimulative effect of low-power laser in vitro. In contrast, stimulation of cancer cells by laser light has not been investigated extensively. The present study attempted to evaluate whether or not human tumor cells could exhibit an increase in colony-forming capability following low-watt laser irradiation. LoVo and HT29 (colon carcinoma), MCF7 (breast carcinoma), M14 and JR1 (malignant melanoma) cell lines were irradiated at different doses of light delivered from an argon or an argon-dye laser. Radiant exposures between 4.2 and 150 kJ/m2 at irradiances ranging from 35 to 500 W/m2 were delivered. Results were mixed. Of the 41 experiments performed, five showed a significant statistical increase in the number of colonies (P less than 0.05), whereas three showed a decrease (P less than 0.05). Nevertheless, the trend of most data was toward an increase in colony formation, and Wilcoxon's signed-ranks test suggested that light increases tumor cell culture growth (P less than 0.03). PMID- 2927232 TI - The first sutureless, laser-welded, end-to-end bowel anastomosis. AB - The use of laser energy to weld together tissue offers great promise in the expanding field of laser surgery. The published results of laser welding intestinal tissue have, to date, been limited to the successful laser closures of small enterotomies. This is the first report of using laser energy alone to create an end-to-end small bowel anastomosis. A biocompatible, water-soluble, intraluminal stent was employed during the laser welding of this sutureless, stapleless ileal anastomosis in a rabbit model. Excellent recovery and healing were observed. The rapidity, ease, and potential for full precision automation of laser welding mandates further research. PMID- 2927233 TI - Laser vaporization of leiomyoma of the esophagus. AB - We present the case of a 67-year-old man with a stenosing leiomyoma of the esophagus, which led to dysphagia. Because of severe concomitant diseases, thoracotomy was not possible in this patient. Endoscopic laser ablation was a fast and successful treatment; more than 2 years have passed without any sign of recurrence. PMID- 2927234 TI - [The value of tumor markers in colorectal cancer]. AB - In 137 patients with colorectal carcinoma carcinoembryonic antigen (CEA) was preoperatively measured in serum. Sensitivity of CEA was dependant on the tumor stage. Patients in early tumor stages (TNM stages I + II) demonstrated only in 10% grossly elevated CEA levels compared with 43% of patients with progressive tumor stages (TNM III + IV). The main importance of tumor markers lies still in postoperative follow-up. In patients with a local recurrence of colorectal carcinoma we measured in 57% CEA levels greater than 10ng/ml, in patients with distant metastases even in 75%. CA 19-9 achieved a lower sensitivity in postoperative follow-up of colorectal carcinoma than CEA. Only 22% of patients with a recurrence of colorectal carcinoma had CA 19-9 levels beyond the normal range (37 U/ml) compared with 67% elevated CEA levels in the same group of patients. CEA is still the most important tumor marker in colorectal carcinoma. Measurement of CA 19-9 in postoperative follow-up is no substitute for CEA, it can only be a supplement. PMID- 2927235 TI - [Quality assurance of prevention by structured continuing education]. PMID- 2927236 TI - [A case presenting differential diagnostic difficulties in eosinophilic gastritis]. AB - The diagnosis of eosinophilic gastritis in a 45 year old man was definitely established only through laparotomy, after inconclusive radiological, endoscopical and biopsy histological findings. The diagnostic difficulties in this particular case were characteristic for this condition, as evident from the literature. PMID- 2927237 TI - [Qualification and quality assurance measures]. PMID- 2927238 TI - Effect of synthetic physalaemin on splanchnic circulation in dogs. AB - Physalaemin has been reported as one of the most potent vasodilator and hypotensive peptides (1-4). In spite of these studies, however, the effect of the peptide on splanchnic circulation is not known precisely. In the present study, the effect of synthetic physalaemin on superior mesenteric arterial blood flow, portal venous blood flow and pancreatic capillary blood flow was investigated in dogs. Dose dependent increases of superior mesenteric arterial blood flow and portal venous blood flow were induced in response to physalaemin (0.1-10.0 ng/kg). Superior mesenteric arterial blood flow and portal venous blood flow attained maximal increases of 77 +/- 8.9% and 70 +/- 8.6%, respectively, at a dose of 5 ng/kg. Physalaemin caused a dose-related decrease in systemic arterial blood pressure. Pancreatic capillary blood flow did not show significant change with the administration of physalaemin. These data suggest that physalaemin may play some physiological roles in the regulation of splanchnic circulation. PMID- 2927239 TI - Effects of oxygen deprivation on incubated rat soleus muscle. AB - Isolated soleus muscle deprived of oxygen produces more lactate and alanine than oxygen-supplied muscle. Oxygenated muscle synthesized glutamine, while anoxic muscle used this amino acid. Oxygen deprivation decreased adenine nucleotides leading to the efflux of nucleosides. Protein synthesis and degradation responded differently to anoxia. Synthesis almost completely ceased, while proteolysis increased. Therefore, protein degradation in soleus muscle is enhanced when energy supplies and oxygen tension are low. PMID- 2927240 TI - Stereospecific reversal of nitrous oxide analgesia by naloxone. AB - The opiate antagonist naloxone was found to block nitrous oxide analgesia in a stereospecific fashion. Using a modified hotplate test in mice, the (-) enantiomer of naloxone (which has a KD of approximately 1 nM for opiate receptors) antagonized the analgesic actions of nitrous oxide in a dose-dependent (2.5-20 mg/kg) fashion. In contrast, the (+)-enantiomer (KD approximately 10,000 nM) had no effect on nitrous oxide analgesia at the highest dose tested (40 mg/kg). These data strongly suggest that nitrous oxide analgesia is mediated via opiate receptors and is consistent with the hypotheses that this effect occurs either through the release of endogenous opioids or by physical perturbation of the opiate receptors. PMID- 2927241 TI - Thermoregulatory effects of resiniferatoxin in the mouse: comparison with capsaicin. AB - Resiniferatoxin, an extremely irritant diterpene present in several members of the genus Euphorbia, produced an 8 C decrease in the rectal temperature of mice with an effective dose in the range of 2-20 micrograms/kg. The structurally related natural product capsaicin produced a similar magnitude of fall in body temperature, albeit with 1000-fold lower potency. Tolerance to the hypothermic effects of both compounds readily developed and cross-tolerance between the compounds was observed. The extreme potency of resiniferatoxin should facilitate biochemical analysis of the mechanism of action of this class of compounds. PMID- 2927242 TI - Effects of caerulein + haloperidol on amphetamine-induced locomotor stereotypy in rats. AB - The combination of haloperidol + caerulein has been reported to produce a long lasting reduction of amphetamine-induced hyperlocomotions in rats. This study was designed to replicate those findings and to determine whether haloperidol + caerulein produce any unique effect on amphetamine-induced locomotor stereotypy. In two experiments, haloperidol + caerulein failed to produce a long-lasting reduction in amphetamine-induced hyperlocomotions. Although haloperidol reduced the locomotor stereotypy produced by higher doses of amphetamine, caerulein had no effect, either alone or combined with haloperidol. PMID- 2927244 TI - Quantitative detection of rapid motions in spectrin by NMR. AB - Previous high resolution proton NMR data on human erythrocyte spectrin molecules has indicated the existence of regions exhibiting rapid internal motions within the intact molecules [L. W.-M. Fung, H.-Z. Lu, R. P. Hjelm, jr, M. E. Johnson, FEBS Lett., 197, 234 (1986)]. We have extended the studies by developing quantitative NMR methods to determine the fraction of spectrin protons exhibiting rapid internal motions, in both the isolated molecule and within the spectrin actin network. Using both one-pulse and spin echo pulse sequences, we find that the fraction of the protons in rapid motion is about 15% of the total protons in the spectrin molecule at 37 degrees C in phosphate buffer with 150 mM NaCl at pH 7.4. Quantitative information on these rapid motions will be important in understanding the structural, mechanical and functional properties of spectrin molecules, as well as in understanding filamentous protein structures in general. PMID- 2927243 TI - Increased serotonin2 (5-HT2) receptor binding as measured by 3H-lysergic acid diethylamide (3H-LSD) in the blood platelets of depressed patients. AB - 3H-Lysergic acid diethylamide (3H-LSD) binding, a putative measure of 5-HT2 receptor binding, was studied in the blood platelets of 29 depressed patients and 24 normal controls. The Bmax (maximum number of 3H-LSD binding sites) in the blood platelets of depressed patients was significantly greater than that of normal volunteers. This increase in Bmax was due to an increase in female depressed patients only. Bmax was significantly lower in female compared to male normal controls but there was no difference between male and female depressed patients. There was also no difference in Kd (an inverse measure of affinity of 3H-LSD binding to its sites) between normal controls and depressed patients. The correlations between Bmax of 3H-LSD binding and the Bmax of the 3H-imipramine binding site or the Vmax of 5-HT uptake sites were not significant. The role of serotonergic processes in the psychobiology of depression is discussed. PMID- 2927245 TI - Redistribution of haloperidol after electroshock: experimental evidence. AB - We have previously reported that plasma and red blood cell levels of haloperidol, a neuroleptic agent, significantly increased immediately after electroconvulsive shock therapy (ECT) in schizophrenic patients on long term haloperidol treatment. To elucidate the mechanism of this increase, we attempted to reproduce this phenomenon in female Wistar rats. After 4 successive days of ip administration of haloperidol (10 mg/kg body weight, once daily), rats were given ECT through corneal electrodes on the fifth day (a.c. 50 Herz, 55 mA, 2.0 sec). Haloperidol levels were determined in plasma and other major tissues using a radioreceptor assay for haloperidol distribution before and after ECT at appropriate time intervals. Plasma haloperidol level was significantly increased 1 min after ECT but tended to return to the control level (without ECT) after 5 min. A significant decrease in haloperidol concentration in tissues was not observed in any of the tissues examined including frontal cerebrum, striatum, and muscle tissues (gluteal muscles). However, the relatively high haloperidol level and the large volume of muscle tissues suggested that the muscle could be the source of the transient increase in haloperidol levels in plasma. This conclusion was also supported by the data showing no significant rise of plasma haloperidol level after ETC in rats previously given a muscle relaxant, succamethonium chloride. PMID- 2927246 TI - Tissue distribution of bufuralol hydroxylase activity in Sprague-Dawley rats. AB - This study has characterised the distribution of bufuralol 1'-hydroxylase activity in various organs of male and female Sprague-Dawley rats. Microsomes were prepared from the liver, kidney, brain, kidney, spleen and adrenals of male and female rats. Measurement of 1'-hydroxybufuralol produced by the incubation of racemic, (+) and (-) bufuralol with the microsomes was by HPLC. The specific activity (nmol/min/mg protein) of bufuralol 1'-hydroxylase in various tissues were: liver (M 12.3; F 10.2), kidney (M 12.3; F 11.7), brain (M 8.9; F 9.0), adrenal (M 0.9; F 0.3), lung (M 4.6; F 3.6) and spleen (M 8.8; F 10.0). Stereoselective preference (+/-) of the isozyme for (+) bufuralol was: Liver (M 2.2; F 2.2), kidney (M 2.2; F 2.1), brain (M 1.0; F 0.9), lung (M 0.74; F 0.95) and spleen (M 1.0; F 1.32). PMID- 2927247 TI - Failure of zinc to prevent dysmorphogenesis of cultured rat conceptuses by anti yolk sac antiserum. AB - Day 10 rat conceptuses were cultured for 48h in the presence of either cadmium or anti-visceral yolk sac antiserum (AVYS). Cadmium was embryotoxic at concentrations exceeding 0.25 micrograms/ml whilst AVYS caused embryonic dysmorphogenesis, particularly affecting the optic vesicles, at concentrations of 2 microliters/ml and above. The effect of pretreatment with zinc on embryotoxicity caused by cadmium or AVYS was studied. Zinc ameliorated the effects of cadmium but had no effect on AVYS-induced embryonic abnormalities. In a second set of experiments inhibition of 125I-labelled PVP uptake by the yolk sac of cultured whole conceptuses was studied. Cadmium and AVYS both inhibited uptake compared to control cultures. Zinc again ameliorated the effect of cadmium but had no action against AVYS-induced inhibition. These results are in contrast to our previous findings using isolated cultured yolk sacs in which zinc ameliorated the inhibitory effects on 125I-labelled PVP uptake of both cadmium and AVYS. These data show that in experiments using the isolated cultured yolk sac and the intact cultured conceptus, a qualitatively different response in yolk sac behaviour is observed under similar experimental conditions. PMID- 2927248 TI - Effects of morphine and naloxone on feline colonic transit. AB - The effects of endogenous and exogenous opioid substances on feline colonic transit were evaluated using colonic transit scintigraphy. Naloxone (0.3 mg/kg, i.m.) accelerated emptying of the cecum and ascending colon, and filling of the transverse colon. Endogenous opioid peptides thus appear to play a significant role in the regulation of colonic transit. At a moderate dose of morphine (0.1 mg/kg, i.m.), cecum and ascending colon transit was accelerated, while at a larger dose (1.0 mg/kg, i.m.) morphine had no effect. Since naloxone, a relatively nonspecific opioid antagonist, and morphine, a principally mu opioid receptor agonist, both accelerate proximal colonic transit, a decelerating role for at least one of the other opioid receptors is inferred. PMID- 2927249 TI - Role of opioid antagonists in treating intravenous cocaine abuse. AB - Intravenous cocaine abuse is a major probel in opioid abusers including those treated in methadone maintenance. Studying 138 opioid addicts, we found that speedballing by combining opioid agonists with cocaine may be blocked by opioid antagonists such as naltrexone and by partial antagonists such as buprenorphine. With both these treatments cocaine abuse was five to eight times less than with methadone treatment. PMID- 2927250 TI - Mechanisms underlying the supra-maximal thermogenesis elicited by aminophylline in rats. AB - Previous studies showed that acute treatment with aminophylline (AMPY) significantly elevated maximum thermogenesis and improved cold tolerance in rats and man in severe cold. However, the exact mechanism by which AMPY enhances thermogenesis was unknown. Rats receiving enprofylline (ENPRO) (1.5 and 15 mg/kg, i.p.), a selective phosphodiesterase inhibitor, failed to show enhanced thermogenesis. In contrast, treatment with a selective adenosine receptor antagonist, 8-phenyltheophylline(8-PT; 2.5 to 10 mg/kg, i.p.), significantly increased (p less than 0.05) thermogenesis and cold tolerance. However, the maximal thermogenic effect by optimal dose of 8-PT (5 mg/kg) was significantly lower than that with optimal dose of AMPY (18.7 mg/kg, i.p.); the deficit could be eradicated by combining optimal 8-PT dose with a low dose of AMPY (1.25 mg/kg), but not with ENPRO. These results indicate that the thermogenic effect of AMPY is not by inhibition of phosphodiesterase but at least partially by antagonism of adenosine receptors. It is also apparent that older mechanisms in addition to adenosine antagonism are also involved in AMPY's thermogenic action. PMID- 2927251 TI - Comparative study of cathinone and amphetamine on brown adipose thermogenesis. AB - The effect of cathinone and amphetamine on brown adipose tissue thermogenesis and its modification with propranolol and timolol has been studied in rats. Both cathinone and amphetamine produced significant dose dependent increases in intracapsular brown adipose tissue (IBAT) and rectal temperatures. Amphetamine was found to be three times more potent as compared to cathinone, on a dose basis. Pretreatment of animals with propranolol and timolol individually inhibited cathinone and amphetamine induced hyperthermia. These findings suggest the involvement of beta adrenergic receptors in cathinone and amphetamine induced thermogenesis. PMID- 2927252 TI - Effect of LY53857, a selective 5HT2 receptor antagonist, on 5HT-induced increases in cutaneous vascular permeability in rats. AB - Both serotonin and histamine increased cutaneous vascular permeability in rats; however, serotonin was approximately 100-fold more potent than histamine. LY53857 (0.1 and 1.0 mg/kg, i.p.), a selective 5HT2 receptor antagonist, blocked serotonin- but not histamine-induced increases in cutaneous vascular permeability. the alpha 1 receptor antagonist, prazosin, did not significantly affect increases in vascular permeability produced by serotonin. These data extend previous studies with LY53857 by further documenting its selectivity as a 5HT2 receptor antagonist. In addition, these results with a selective 5HT2 receptor antagonist provide evidence that 5HT2 receptor activation may be the predominant mechanism associated with vascular permeability changes induced by serotonin. PMID- 2927253 TI - Suppression of opiate withdrawal by cyclosporin A and dietary modification. AB - It has been demonstrated in a murine model that a defined diet (Purina Basal Diet 5755) has immunosuppressive effects similar to cyclosporin A (CsA). It was also shown that CsA treatment in opiate dependent rats can attenuate the severity of opiate withdrawal. In this study, an opiate dependence model was established in Balb/c mice to assess the effects of the 5755 diet and CsA on morphine withdrawal - a CNS mediated phenomenon. Three groups of mice were used; a chow-fed control group (Purina 5008), a chow fed CsA treated group, and a group maintained on the 5755 diet. Morphine dependence was established by subcutaneous implantation of a 100 mg morphine base pellet under ether anesthesia. Seventy-two hours after pellet implantation, withdrawal was precipitated by a single injection of the opiate antagonist naloxone (2 mg/kg ip). Two indicators of withdrawal were assessed; jumping and diarrhea. The data demonstrated that both CsA and the 5755 diet resulted in significant attenuation of withdrawal symptoms with the 5755 diet being the most effective of the two. These findings suggest that immune modulation elicited by the 5755 diet and CsA treatment has a direct impact on the CNS opioid function. PMID- 2927254 TI - Magnesium potentiation of iron-transferrin binding. AB - The binding of iron to transferrin was studied by loading iron (III) onto apotransferrin in a chloride and a nitrilotriacetate form. When magnesium was added, a marked increase occurred in both the rate of iron binding and the maximum level of iron loaded on transferrin utilizing either iron salt. In the absence of magnesium the amount of iron required to achieve 50 percent saturation of the binding sites was 1.6 x 10(-4) M, whereas when magnesium was added, only about one-third as much iron (0.54 x 10(-4) M) was required. These data suggest an allosteric effect on transferrin by magnesium which potentiates iron (III) binding. PMID- 2927255 TI - Factors influencing erythrocyte choline concentrations. AB - Choline concentrations in human erythrocytes increase after freezing and thawing, during incubation in Krebs-phosphate for 30 min or on storage at 0 degrees C for 3-24 hr. The increase is prevented by protein precipitation by 10% perchloric acid, 10% zinc hydroxide, 10% sodium tungstate or boiling in water. It is not prevented by EDTA (10 mM) and is increased by oleate (5 mM). We suggest that the increase is due to the action of phospholipase D on erythrocyte phospholipids. PMID- 2927256 TI - The generation of valosin-like peptides from a precursor protein in vitro as an extraction artifact. AB - Valosin is a 25 amino acid peptide recently isolated from the porcine gastrointestinal tract. The molecular forms of valosin-like immunoreactivity (VLIR) were examined following different tissue extraction procedures. Fractionation of tissue extracted with cold 0.1 M sodium hydroxide by Sephadex G50 gel permeation chromatography revealed a large form of VLIR (Kav = 0). Smaller forms of VLIR, Kav = 0.36 and 0.57 were obtained in tissue extracted by boiling in 0.5 M acetic acid. Acidification and boiling of the 0.1 M sodium hydroxide tissue extracts also generated smaller forms of VLIR of Kav = 0.36 and 0.57. Partially purified preparations of the large forms of VLIR extracted with sodium hydroxide could be disrupted into a smaller form of Kav = 0.57 by acidification and boiling. This smaller molecular form co-eluted with the synthetic 25 amino acid valosin standard. We conclude that valosin does not occur naturally but is an artifact generated by cleavage of a larger protein precursor upon acid extraction of tissues. Workers should be aware of the need to verify their extraction procedures when characterising novel peptides to avoid potential pitfalls such as acid/thermal cleavage of proteins. PMID- 2927257 TI - Cholinergic responsiveness of intestinal muscle in the pregnant guinea pig. AB - Clinical observations and limited animal experiments have suggested that gastrointestinal motility is suppressed during pregnancy. We therefore compared isometric contractions of colon and ileal circular muscle in response to carbachol (10(-8) to 10(-4) M). Data was analyzed by comparing mean maximal tension, dose-response curves, and EC50 values for tissue from the two groups of animals. Circular muscle from proximal colon, distal colon, and ileum in pregnant animals developed less tension in response to carbachol than did tissue from non pregnant controls. Dose-response curves in the pregnant groups were depressed, when compared with non-pregnant groups, at concentrations of 10(-6) M and greater. Sensitivity of the muscle to cholinergic stimulation, as measured by EC50 values, was similar in the ileum and proximal colon but increased slightly (p less than 0.05), by a factor of approximately 2, for distal colonic muscle from pregnant animals. Assuming that circular muscle contractions are primarily responsible for mixing and propulsion in the gut, this reduction in responsiveness to excitatory cholinergic stimulation is consistent with the concept of pregnancy-related suppression of gastrointestinal motility. PMID- 2927258 TI - Cholecystokinin stimulates neuronal receptors to produce contraction of the canine colon. AB - The motor effects of cholecystokinin 26-33-amide (CCK octapeptide; CCK-OP) and several purported CCK receptor antagonists on canine colonic circular muscle were determined in pentobarbital anesthetized dogs. Intravenous injections of CCK-OP had no effect on colonic motility at doses that contracted the gallbladder, stomach and duodenum. CCK-OP delivered by intraarterial injection to a small segment of the proximal colon produced a dose related increase in colonic motility with one-half maximum response at 12 ng/Kg and maximum response at 50 ng/Kg. The effects of intraarterial injections of several established CCK receptor antagonists on proximal colonic responses to intraarterial injections of CCK-OP were determined. Proglumide, 10 mg/Kg, did not produce colonic contractions itself, but antagonized CCK-OP-induced responses. Carbobenzyloxy (CBZ)-CCK27-32-amide antagonized CCK-OP-induced colonic responses and also had no effect on basal colonic motility (0.1-1 and 5 micrograms/Kg). Neither compound antagonized acetylcholine- induced colonic responses. Butoxycarbonyl (BOC)-CCK31 33-amide increased basal colonic motility, but did not alter CCK-OP-induced responses at doses of 0.1 and 0.2 mg/Kg. Dibutyryl-cGMP at a dose of 0.1 mg/Kg did not affect basal motility or CCK-OP-induced contractions. At a dose of 1.0 mg/kg it increased basal colonic motility but did not affect CCK-OP-induced contractions. Pentagastrin increased colonic motor activity only at a dose of 5 micrograms/Kg, i.a., a much higher dose than effective doses of CCK-OP. The mechanism of CCK-OP-induced colonic motor effects also was determined. Atropine sulfate, 100 micrograms/Kg, i.v. significantly reduced both intraarterial acetylcholine-and CCK-OP-induced maximum colonic contractions. Tetrodotoxin, at intravenous doses that completely block neuronal activity, did not affect maximum acetylcholine-induced contractions but practically eliminated maximum CCK-OP induced maximum colonic responses. In conclusion, intraarterial CCK-OP produces circular muscle contraction of the canine proximal colon that is mediated by stimulation of specific CCK receptors which produce the release of acetylcholine from cholinergic enteric neurons. Proglumide and CBZ-CCK27-32-amide are effective CCK receptor antagonists at these colonic neuronal receptors. PMID- 2927259 TI - Effects of caffeine on social behavior, exploration and locomotor activity: interactions with ethanol. AB - The effects of caffeine and its interaction with ethanol were examined in a test of social behavior and a holeboard test of exploration and locomotion. Male mice were injected i.p. with 15, 30 or 60 mg/kg caffeine alone or in combination with 2 g/kg ethanol. The animals were then put in pairs into a familiar arena, or examined individually in the holeboard. Only the highest dose of caffeine (60 mg/kg) had a significant effect on the time spent in social interaction and motor activity in the social behavior test: both measures were reduced. The duration and frequency of avoidance-irritability behavior was dose-dependently increased by caffeine. In the holeboard, caffeine caused a dose-dependent increase in locomotor activity. 30 mg/kg caffeine reversed the ethanol-induced reduction of time spent in social interaction, and 60 mg/kg caffeine antagonized the ethanol induced increase in locomotor activity in both the social behavior and holeboard tests. Caffeine's effects on ethanol-induced behavioral changes are compared with those of other drugs. PMID- 2927261 TI - Chain length-dependent interaction of free fatty acids with the erythrocyte membrane. AB - Free fatty acids protect erythrocytes against hypotonic haemolysis in a certain low concentration range and become haemolytic at higher concentrations. The chain length dependence of this biphasic behaviour was investigated using human erythrocytes. The results can be summarized as follows: (i) A critical minimum chain length is required for both effects. Octanoic acid (C8) and fatty acids with a shorter chain length do not have any effect on the osmotic resistance of erythrocytes. (ii) Decanoic acid (C10) decreases the extent of hypo-osmotic haemolysis and does not become haemolytic at higher concentrations. (iii) Dodecanoic acid (C12) represents the minimum chain length for the typical concentration-dependent biphasic behaviour with protection against hypo-osmotic haemolysis at a certain low concentration range and subsequent haemolysis at higher concentrations. (iv) Tetradecanoic acid (C14) exhibits two concentration ranges of protection against hypo-osmotic haemolysis, each followed by haemolytic concentrations. (v) The observed effects are not correlated with the critical micellar concentrations of the investigated fatty acids. PMID- 2927260 TI - Effect of gamma 3 or gamma 2 melanocyte stimulating hormone on steroidogenesis in the fetal sheep during late gestation. AB - We have measured circulating concentrations of gamma 3 Melanocyte Stimulating Hormone (MSH) in fetal sheep between 111 and 145 days gestation. There was no significant effect of gestational age on the fetal plasma concentrations of gamma 3 MSH throughout this period. We have examined the role of gamma-MSH related peptides in the control of fetal adrenal steroidogenesis and found no significant change in fetal plasma cortisol or pregnenolone concentrations during a 60-72 h infusion of saline, gamma 2 MSH or gamma 3 MSH in sheep between 130 and 135 days gestation. Therefore although we have demonstrated the presence of gamma MSH related peptides in fetal sheep plasma during late gestation we have failed to demonstrate a role for gamma 3 or gamma 2 MSH in the changes in fetal steroid concentrations which occur prepartum. PMID- 2927263 TI - Concerns about the use of portable cholesterol analyzers. AB - While there is growing interest and concern about the role of portable cholesterol analyzers in clinical practice, the evidence on the effectiveness of these devices is limited. It has been shown that a number of factors can affect the validity of the cholesterol readings. We present a cautionary view on use of these devices. PMID- 2927262 TI - Alterations in amphetamine-induced locomotor activity and stereotypy after electrical stimulation of the nucleus accumbens and neostriatum. AB - The exacerbation of the locomotor and stereotypic effects of amphetamine after repeated drug administration is well documented. To elaborate on the involvement of the nigrostriatal and mesolimbic dopamine (DA) systems in modulating behavioral sensitization, locomotor activity and the time spent engaged in repetitive stereotyped behaviors following systemic amphetamine injection were assessed after electrical stimulation of the nucleus accumbens and neostriatum. It was found that exposure to repeated sessions of high frequency, low current stimulation of the anteromedial neostriatum and nucleus accumbens significantly enhanced the locomotor excitation induced by administration of 3.0 mg/kg of amphetamine. Stereotypic behaviors were also modified as a function of electrical stimulation of these brain regions, with the development of a significant decrease in the duration of focused head and body movements corresponding to the facilitated locomotor effects of the drug. Taken together, these data provide additional evidence demonstrating the interdependent relationship between amphetamine-elicited locomotor activity and stereotypy, and were discussed in terms of a functional interaction between mesolimbic and nigrostriatal systems in determining the behavioral profile of amphetamine administration. PMID- 2927264 TI - Cytopathology: new legislative, regulatory, and proficiency testing requirements. AB - In 1988, a combination of efforts by the press, the Maryland General Assembly, the Department of Health and Mental Hygiene (DHMH), and an advisory panel of pathologists and cytotechnologists led to broader and stricter regulation of cytopathology laboratories in Maryland. A new law called for standards covering the maximum number of slides a cytotechnologist may examine, unsatisfactory specimens, slide and records retention, a limitation on the use of out-of-state laboratories by Maryland physicians, and a mandatory, state-run proficiency testing program. Maryland's proficiency testing program is modeled on that of New York State but incorporates improvements in diagnostic definitions, testing mechanisms, and retraining requirements. PMID- 2927265 TI - Prehospital care and the community hospital as a base station. AB - In Maryland's coordinated, regionalized emergency medical system, prehospital care is given to an injured or ill person at home, on the street, or in a doctor's office before the patient is transported to a hospital. Prehospital care of patients has advanced significantly since the federal government passed emergency medical service (EMS) legislation in 1966. In Maryland there are several functioning levels of prehospital care providers who perform skills unique to their particular environment and training. It is reasonable for all hospitals operating a full-service Emergency Department to consider becoming base stations for consultation to prehospital care providers bringing patients to that hospital. This is well within the province of the Emergency Medicine specialist and will provide improved service to patients. PMID- 2927266 TI - Methodologic approach for a large functional trauma registry. AB - The utility of a clinical trauma registry (TR) is directly related to the constituents of the data base and to the accuracy of the data, which is contingent on a carefully constructed data collection system. A TR was developed by traumatologists at a busy Level I trauma facility that predominantly receives patients having incurred blunt injury. Four dedicated data collectors gather the AP information within 24 to 48 hours after admission, with prompt Attending Surgical review for verification. Examples of data output prove this is a functional system. Using a careful methodologic approach for design and implementation, clinicians can create a large, functional trauma registry with many potential applications. PMID- 2927267 TI - Use of health and rehabilitation services following head injury. AB - The impact on public health of head injury as a major source of death and disability, especially among adolescents and young adults, is well recognized. In Maryland the primary annual incidence of head injury severe enough to result in death or hospitalization has been estimated to be 149 per 100,000 population. These figures are comparable to national and other regional estimates reported in the literature. Improvements in the acute care management of head injury have generally led to improved survival. PMID- 2927268 TI - Medical care behind bars: Maryland prison system. AB - The inmate population in the Maryland prison system has increased dramatically over the past 10 years due to changes in sentencing by the courts. At the same time, costs of inmate health care have increased markedly following court cases mandating adequate care, an amelioration of prior inadequate standards of care. The unique demographic and disease risk characteristics of inmates predispose them to a distinct set of health problems. The state is legally obligated to provide health care to individuals sentenced to confinement in state prisons. It is often the first care these individuals have received in many years. PMID- 2927269 TI - AIDS as a cause of dementia in the elderly. AB - Acquired Immune Deficiency Syndrome (AIDS) is frequently complicated by central nervous system (CNS) involvement. Progressive dementia is an increasingly recognized manifestation of AIDS-associated neurologic syndromes. PMID- 2927270 TI - [Multifractionated radiotherapy of esophageal cancer]. AB - The authors investigated the effectiveness of multifractionated radiotherapy with a daily dose (2-2.2 Gy) divided into equal fractions provided to 42 esophageal cancer patients. The total focal dose was 40-70 Gy. Most of the patients were at the age of over 50, stage T3-4 was established in 83%. Multifractionated irradiation was shown to reduce the frequency and severity of general and local radiation reactions, maintaining a therapeutic effect. Owing to improved tolerance of the treatment, the number of patients eligible for radical radiotherapy was on an increase. It permitted the improvement of immediate therapeutic results and an increase in the mean survival of patients with a good immediate therapeutic result. Complete tumor regression, detected on x-ray, was achieved in 31%, and in the use of the common method--in 20% only. The above method should be regarded as a sparing one to be used for the treatment of weakened patients and patients with associated pulmonary and cardiovascular diseases. PMID- 2927271 TI - [Combination treatment of rectal cancer using preoperative combination radiotherapy]. AB - The paper is concerned with analysis of the results of therapy of 122 rectal cancer patients divided into 2 groups by sex, age, tumor site, type of anatomical tumor growth, and stage of disease: I (72 patients)--combined therapy including preoperative radiotherapy and operation; II (50 patients)--surgery alone. Indications for combined therapy with preoperative irradiation were worked out. The results of histological investigation showed that this method brought about deep radiation injuries of tumors with minimum damage of the adjacent normal tissues. A conclusion was made that combined therapy including preoperative irradiation decreased the number of recurrences and metastases and increased (in combination with surgical intervention) the 5-year survival rate up to 79.6%. PMID- 2927272 TI - [Acute radiation injuries of the brain developing during radiotherapy]. PMID- 2927273 TI - [Electrocardiographic evaluation of the reactions of the myocardium during irradiation of the thorax]. PMID- 2927274 TI - [An economic analysis of gamma teletherapy]. AB - The paper is concerned with comparative economic analysis of different types of organization of teletherapy. Considerable economic advantages of the operation of teletherapy units in 2 shifts as compared to that in one shift and a 7-day schedule as compared to a 5-day schedule were shown. Using economic reserves, one can considerably expand the volume of radiological service without great extra expenditures. PMID- 2927275 TI - [Internal irradiation doses in patients during the diagnostic use of colloidal radiopharmaceutics]. AB - The assessment of the human organs and body systems exposed to radiation was based on the investigation of colloidal radiopharmaceuticals employed in the USSR for liver and spleen visualization. Seven radiopharmaceuticals (functional analogs: 3 were imported to the USSR, 4--made in this country) were investigated. Pharmacokinetics of the agents was studied by a human counter that permitted obtaining quantitative data on their distribution and elimination from the body. A computerized program based on the heterogeneous model of a "standard" man. Dose calculation results have shown that the critical organ for all investigated radiopharmaceuticals is the liver, the radiation dose in it being at 90-120 microSv/MBq and the mean effective equivalent dose at 14 +/- 1 microSv/MBq. PMID- 2927276 TI - [Scintigraphy of the mediastinum using 67Ga citrate in lymphogranulomatosis in children]. AB - Scintigraphic semiotics of the involvement of the intrathoracic lymph nodes in children with Hodgkin's disease permitted differentiated assessment of the state of each group of the mediastinal lymph nodes and root of the lung over time. Knowledge of the characteristic features of 67Ga-citrate scintigraphic distribution with relation to the mediastinum after therapeutic measures makes it possible to exclude false positive results and to define the correct time for monitoring. PMID- 2927277 TI - [Comparison of the results of x-ray, endoscopic and radionuclide studies of deforming bronchitis]. AB - Comprehensive investigation including panoramic chest x-ray, tomography, bronchofibroscopy with biopsy, bronchography, and comprehensive radionuclide investigation, were used in 233 patients with deforming bronchitis. All the patients were divided into 3 groups. Endoscopic findings corresponded to the results of comprehensive radionuclide investigation in all the groups. PMID- 2927278 TI - [Dynamics of the x-ray picture of bone metastases of thyroid cancer as affected by radiotherapy]. AB - Teletherapy or radiotherapy combined with 131I for thyroid cancer metastases to the bones caused the development of bone reparation in 70%, in 17% the picture remained unchanged; signs of further tumor growth were observed in 13%. An early x-ray sign of therapeutic efficacy was the decreased soft tissue component of a metastatic tumor 3-5 mos after the initiation of therapy. Disease stabilization was observed in 2.5-3 yrs. X-ray manifestations of bone reparation looked as sclerotic changes along the periphery of a focus of lesion and depended on the sizes of a metastasis and its localization in the skeleton. PMID- 2927279 TI - [Study of local capillary circulation using labeled albumin microspheres during osteotomy of the maxilla (experimental study)]. AB - The authors presented the results of experiments on 14 random bred dogs in whom fragmentary osteotomy of the maxilla at the level of 7 perpendicular 7 teeth was performed with subsequent investigation of the volumetric blood flow rate in soft and osseous tissues of the osteotomized fragment using labeled albumin microspheres. The animals were divided into 4 groups (the study group and control groups). The volumetric blood flow rate was investigated over time with the monitoring of the CV system 1 (the 2nd group), 6 (the 3rd group) and 24 h (the 4th group) after operation. The total reduction of the blood flow in the tissues of the osteotomized fragment as compared to that of the control group was 54.5% (in the 1st group), 39.3% (in the 2nd group) and 41% (in the 3rd group). The results of the study showed correlation between the blood flow rate reduction in the soft tissue structures and osseous tissue. PMID- 2927281 TI - [Experience in the program-directed postgraduate teaching of specialists in clinical radiology]. PMID- 2927280 TI - [Pathomorphology of the results of chronic irradiation from a gamma-neutron source implanted in the abdominal cavity]. AB - Comparison of the results of morphological investigations of the internal organs of dogs and sheep with gamma-neutron radiation sources, implanted in the abdominal cavity, has shown that the correlation between a degree of severity and type of morphological changes in this case is similar to that of identical irradiation from an external source. PMID- 2927282 TI - Partial purification and characterization of a neurite-promoting factor from the injured goldfish optic nerve. AB - We have partially purified and characterized a neurite-promoting factor derived from the injured goldfish optic nerve (ON). This factor is secreted into conditioned media (CM) by the injured, but not intact goldfish ON, and has potent outgrowth-promoting effects on neurons of the embryonic mammalian brain. Based on its elution properties on ion-exchange and gel-filtration chromatography, this factor appears to be an acidic protein of Mr ca. 26 kilodaltons (kDa) that is distinct from previously characterized growth factors with described effects on mammalian CNS neurons. PMID- 2927283 TI - Estrogen regulation of proenkephalin gene expression in the ventromedial hypothalamus of the rat: temporal qualities and synergism with progesterone. AB - Estrogen has been shown to increase proenkephalin (PE) mRNA levels in neurons of the ventrolateral aspect of the ventromedial hypothalamic nucleus (VL-VM). In this series of experiments, we examined the temporal qualities of this induction by determining both the latency of the estrogen-induced elevation in PE mRNA levels and the rate at which the message levels decline following removal of estrogen. In addition we have examined the effects of progesterone on PE gene expression in the VL-VM of estrogen-primed rats. The latency of the estrogen induced elevation in PE mRNA levels was found to be relatively short: PE mRNA levels were increased 2-fold within 1 h of estrogen replacement. Following estrogen removal the levels of PE mRNA declined rapidly. Progesterone treatment attenuated this decline, prolonging the estrogen-induced elevation of PE mRNA levels. These results suggest that estrogen rapidly increases PE mRNA levels through a mechanism that probably involves alterations in both the rate of appearance and the rate of degradation of the message. Together, the short latency of the estrogen-induced elevation and the rapid rate of decay following estrogen removal indicate that PE gene expression is highly sensitive to fluctuating estrogen levels. The effect of progesterone suggests that this enkephalinergic system may be regulated by both estrogen and progesterone during the estrous cycle. PMID- 2927284 TI - Characterization of muscarinic acetylcholine receptors in rat cerebral cortex slices with concomitant morphological and physiological assessment of tissue viability. AB - We have begun studies on regulatory mechanisms of muscarinic acetylcholine receptors (mAChRs) in slices of rat cerebral cortex. This paper, the first of two, deals with the viability of the cells in the slices (a prerequisite for studying receptor regulation) and provides a characterization of binding sites for [3H]N-methyl scopolamine ([3H]NMS) and [3H]quinuclidinyl benzylate ([3H]QNB) in this preparation. Trypan blue exclusion tests in 400-microns-thick cortical slices showed a number of dead cells in a 100 microns zone from each cut edge, for a total of about 15-30% of all cells in the slice. In agreement with previous reports, electron microscopy revealed healthy tissue in the middle of the slice, but after incubation for several hours, swollen cells and dendrites were seen without cytoplasmic organelles. Axon terminals, however, were still seen to synapse upon these processes. Electrophysiological single unit recordings showed spontaneous action potentials in the slices. For receptor binding experiments, slices were incubated with either [3H]NMS, a hydrophilic mAChR ligand which does not penetrate the cell membrane, or the lipophilic ligand [3H]QNB which readily enters cells. For both ligands, equilibrium binding was reached after 8 h at 4 degrees C, and after 3 h at 30 degrees C. Binding of both ligands could be displaced by unlabelled atropine sulphate, NMS or QNB. Saturation binding curves yielded a Bmax of 2187 fmol/mg protein for [3H]QNB (reflecting all mAChRs) and 1335 fmol/mg protein for [3H]NMS (only mAChRs on the cell surface) at 30 degrees C. Kd values were 8.2 and 5.2 nM for [3H]QNB and [3H]NMS, respectively. These values are high compared with values obtained from homogenates, frozen sections or dissociated cells, and presumably reflect the use of intact, living tissue. These data are probably a better reflection of the actual, in vivo mAChR number and affinity than those obtained from dead tissue. This slice preparation suggests itself as a simple but effective method with which to study the regulation of mAChRs in living brain tissue. PMID- 2927285 TI - Microtubule-associated proteins MAP5 and MAP1x: closely related components of the neuronal cytoskeleton with different cytoplasmic distributions in the developing brain. AB - Monoclonal antibodies were used to explore the relationship between two similarly sized microtubule-associated proteins (MAPs), MAP1x and MAP5. Although the proteins detected by anti-MAP1x and anti-MAP5 co-migrate in SDS-polyacrylamide gels, the patterns of antigenic proteolytic fragments (epitope maps) derived from them were completely different. The results suggest either that MAP1x is more stable than MAP5 or that the MAP1x epitope is situated close to one end of the molecule and gives rise to a very short proteolytic fragment. Immunoprecipitation from brain supernatants with either antibody brought down protein that cross reacted with the other antibody, indicating that individual molecules bearing both epitopes exist in brain. Peptide maps of the proteins immunoprecipitated with the two antibodies showed that they are closely similar. Despite these similarities, the two antibodies gave different staining patterns on sections of developing rat brain, anti-MAP5 staining both axons and dendrites whereas anti MAP1x stained only axons. We conclude that the MAP5 and MAP1x molecules are very similar, and possibly identical. The difference in staining patterns with the two antibodies could be because there are two proteins present in brain, one in immature axons bearing both the MAP5 and MAP1x epitopes and another with a wider distribution bearing only the MAP5 epitope. Alternatively, there may be a single protein bearing both epitopes, with the MAP1x epitope being masked in neuronal dendrites and mature axons by covalent modification or inter-molecular binding. PMID- 2927286 TI - [Certification as a stimulus for improvement in professional training]. PMID- 2927287 TI - [Chronic kidney failure]. PMID- 2927288 TI - [The sequelae of brain concussion]. PMID- 2927289 TI - [Radon therapy in the USSR. I]. PMID- 2927290 TI - [The economics of public health]. PMID- 2927291 TI - [Complications in radiation therapy]. PMID- 2927292 TI - [The interaction of drugs in simultaneous administration in pediatric practice]. PMID- 2927293 TI - Generalized equation for predicting body density of women from girth measurements. AB - This study's purpose was to develop a generalized regression equation to predict body density in adult women. Subjects, 482 women, were hydrostatically weighed and circumference (girths) recorded for thigh, hips (buttocks), iliac, and abdomen (mean of abdomen 1 and abdomen 2). Age (range = 15-79 yr), weight (38.3 132.9 kg), and height (145.5-186.3 cm) were also recorded. Percent body fat ranged from 12.7 to 63.1%. Stepwise multiple regression was used to select the best set of predictors (from seven) of body density. Capitalization on chance was negligible due to the favorable subject to predictor ratio (57 subjects per predictor). The regression equation (N = 400) developed for predicting body density was: body density = 1.168297 - (0.002824 x abdomen) + (0.0000122098 x abdomen2) - (0.000733128 x hips) + (0.000510477 x height) - (0.000216161 x age) [SEE = 0.009486784 (4.2% body fat), R = 0.889, adjusted R2 = 0.787]. Using this equation on a cross-validation sample (N = 82) produced a predicted mean (+/- SD) of 1.016 +/- 0.017 (validation sample mean = 1.016 +/- 0.021) and a total error (SE) of 0.0082 (3.6% body fat). The use of three girth measurements, height, and age enabled us to develop regression equations to predict body density in women that are comparable in accuracy to those using skinfold calipers and, thus, are a viable alternative. PMID- 2927294 TI - Isokinetic strength and body composition of high school wrestlers across age. AB - The purpose of this study was to determine the changes in body composition as well as absolute and relative isokinetic forearm and leg strength of high school wrestlers across age. One hundred ninety-five wrestlers (means age +/- SD = 16.36 +/- 1.12 yr) volunteered to be measured for strength using a Cybex II dynamometer at 30, 180, and 300 degrees.s-1. In addition, underwater weighing was used to determine body composition characteristics. The subjects were divided into four age groups: group 1 (G1) = 14.17-15.00 yr (N = 20); group 2 (G2) = 15.01-16.00 yr (N = 60); group 3 (G3) = 16.01-17.00 yr (N = 52); and group 4 (G4) = 17.01-18.50 yr (N = 63). One-way ANOVA or ANCOVA with Tukey post hoc comparisons indicated significant (P less than 0.05) changes across age for height, body weight, and fat-free weight, as well as absolute and relative forearm and leg strength. The results of this study indicated that, while a large portion of the improvements in strength across age were associated with increases in lean tissue, there was an additional "age effect" which could not be accounted for by changes in fat free weight. Although the mechanism responsible for the "age effect" is unclear, it is possible that neural development contributed to the strength increases across age. PMID- 2927295 TI - Asymmetries in ground reaction force patterns in normal human gait. AB - The purpose of this study was to propose a measure of symmetry/asymmetry for normal human gait and to quantify symmetries/asymmetries of normal human gait for selected gait variables using a force platform. Sixty-two subjects performed ten gait trials each, stepping on the force platform five times with each leg. From these gait trials a symmetry index was calculated for 34 gait variables. The upper and lower limits of normal gait were calculated such that 95% of all symmetry indices obtained from this subject population fell within these limits. Upper and lower limits were found to vary from +/- 4% to over +/- 13,000%. Extremely high percentages were found for variables which had absolute magnitudes close to zero and/or variables which occurred at distinctly different instants during the gait cycle. The results of these variables need to be interpreted with caution. PMID- 2927296 TI - Coactivation of antagonistic muscle pairs during voluntary agonist contraction induced stretch of the antagonist. PMID- 2927297 TI - Pressure distribution in Morton's foot structure. AB - The Morton foot structure (MFS) is a foot having, as its most prominent distinguishing feature, a second metatarsal head which is more distally placed than the head of the first. This structure has been associated with a variety of foot problems in athletes. The origin of these foot problems has been hypothesized to be an abnormal metatarsal head loading pattern found in the MFS. This study was conducted to determine whether the MFS produced a metatarsal head pressure profile which was different from the non-Morton foot. Plantar pressure distributions during walking were collected using a 1000 element piezoceramic pressure platform from the feet of 45 subjects (30 classified as having the MFS and 15 non-Morton or control subjects). The protrusion of the head of the second metatarsal beyond the first metatarsal head was determined by palpation and varied between 0.8 and 2.8 cm for the experimental group. Pressure distributions were collected from a mid-gait step onto the platform at a speed of 1.6 to 2 m.s 1 using a 15 m runway. Peak pressures and impulse values were determined for three forefoot regions. Results show that peak loading in both groups occurred under the second metatarsal but that the magnitudes of second metatarsal peak pressures were significantly higher in the MFS group (P less than 0.005). The results suggest that, although the loading pattern between MFS and normal feet is similar, the significantly higher second metatarsal head peak pressure in the MFS may predispose this foot type to problems associated with excessive localized pressure. PMID- 2927298 TI - Exercise reverses depressed metabolic rate produced by severe caloric restriction. AB - The effects of caloric restriction and exercise on resting metabolic rate (RMR) were studied in five obese humans. Subjects consumed a 500 kcal.d-1 diet for 4 wk, with the subjects remaining sedentary during the first 2 wk and then exercising 30 min daily at 60% VO2max during the last 2 wk of caloric restriction. After 2 wk of dieting, RMR decreased to approximately 87% of the pre dieting control value. Over the last 2 wk of dieting with the addition of daily exercise, the fall in RMR was reversed as it returned to the pre-dieting level. In summary, daily exercise reversed the drop in RMR associated with severe caloric restriction. PMID- 2927299 TI - Naloxone does not affect muscle blood flow during low intensity exercise in rats. AB - The purpose of this study was to determine whether endogenous opioids are involved in the control of skeletal muscle blood flow during locomotory exercise in rats. The radiolabeled miscrosphere technique was used to measure total and regional muscle blood flow. We first determined whether methionine enkephalin (1,000 micrograms.kg-1 I.V.) would produce vasodilation in muscle vascular beds. We found that methionine enkephalin produced a 36 mm Hg (range of 20-50 mm Hg) drop in mean arterial pressure (Pa), which was associated with decreases in calculated skeletal muscle vascular resistance in anesthetized rats, and that these effects on arterial pressure and skeletal muscle vascular resistance were blocked by the infusion of naloxone (10 micrograms.kg-1). Measurements were then made at 5 min of treadmill exercise at 15 m.min-1 (0 degree incline) and following exercise in both saline-treated (controls) and naloxone (10 micrograms.kg-1)-treated conscious rats. There were no differences between the heart rates, blood pressures, or total muscle blood flows of the two groups. There were also no significant differences between the blood flows to 32 hind limb muscle samples composed of various muscle fiber types. Since naloxone blockade did not affect total or regional muscle blood flow during low intensity exercise, it appears that the endogenous opioids are not required for the normal exercise hyperemia of skeletal muscles. PMID- 2927300 TI - Exercise training bradycardia: the role of autonomic balance. AB - We used an algebraic model of resting heart rate (HRr), HRr-mn (HRo), to compare resting parasympathetic (n) and sympathetic (m) influence, intrinsic heart rate (HRo), and resting autonomic balance (Abal) in ten endurance-trained (ET) and ten nontrained (NT) men. The values of m, n, and Abal were determined by selective pharmacological blockade with atropine and metoprolol. HRo was obtained during double blockade with atropine and metoprolol. HRo and HRr were significantly lower (P less than or equal to 0.04 and P less than or equal to 0.01, respectively) in the ET subjects (79.5 +/- 2.8 beats.min-1 and 54.7 +/- 3.0 beats.min-1, respectively) when compared to the NT subjects (86.6 +/- 2.5 beats.min1 and 70.2 +/- 3.1 beats.min-1, respectively). Parasympathetic influence (n) was greater in the ET subjects (P less than or equal to 0.04), while sympathetic influence (m) was slightly (P less than or equal to 0.05) less in the ET subjects. Consequently, the value of Abal was significantly less in the ET subjects (P less than or equal to 0.02), indicating that resting parasympathetic predominance was significantly greater in the ET subjects. We concluded that the exercise training bradycardia, observed in this group of subjects, was due to both a lower HRo and an Abal with an augmented parasympathetic dominance. PMID- 2927301 TI - Gastric emptying during prolonged cycling exercise in the heat. AB - Eight trained male cyclists (age 20-33 yr) completed four 3-h bouts of cycling at 60% peak VO2 in the heat (33 degrees C) drinking either water (W), 5% glucose (G), 5% glucose polymer (GP), or 3.2% glucose polymer + 1.8% fructose (GP/F) at a rate of 350 ml every 20 min (3.15 l total volume). Similar changes in heart rate, sweat rate, rectal and mean skin temperatures, and plasma [Na+], [K+], and osmolality were observed during all trials. Mean changes in plasma volume, although not significantly different between trials, were lowest for the GP/F drink (-2.6%) and greatest for the G (-8.1%) drink. Plasma volume decreased (P less than 0.05) below pre-exercise control values during the W, G, and GP trails but was maintained at control values during the GP/F trials. In contrast to water ingestion, G, GP, and GP/F ingestion maintained plasma glucose and respiratory exchange ratios throughout the 3-h exercise bouts. Gastric residual volume (GRV) obtained at the end of exercise was similar for the W, GP, and GP/F trials. The G trials yielded greater (P less than 0.05) GRV than W trials. For all drinks ingested, over 90% of the 3.15 l consumed was emptied from the stomach during the 3-h exercise bouts. At a mean sweat rate of 1.2 l.h-1, cyclists replaced 73% of fluid lost and experienced only a 1.6% loss in body weight. This study demonstrates that, during prolonged (3-h) cycling exercise in the heat, large volumes of W and 5% carbohydrate can be emptied from the stomach to help minimize the effects of dehydration. PMID- 2927302 TI - Metabolism and performance following carbohydrate ingestion late in exercise. AB - To determine whether a single carbohydrate feeding could rapidly restore and maintain plasma glucose availability late in exercise, six trained cyclists were studied on two occasions during exercise to fatigue at 70 +/- 1% of VO2max. After 135 min of exercise, the men were fed either an artificially sweetened placebo or glucose polymers (3 g.kg-1 in a 50% solution). Prolonged exercise led to a decline in plasma glucose from 4.6 +/- 0.1 mM at rest to 3.9 +/- 0.2 mM after 135 min (P less than 0.05). Plasma glucose decreased further (P less than 0.05) to 3.2 +/- 2.0 mM at fatigue following placebo ingestion but increased (P less than 0.05) and was then maintained at 4.5-4.9 mM following carbohydrate ingestion. Respiratory exchange ratio (R) fell gradually during the placebo trial from 0.88 +/- 0.01 after 10 min of exercise to 0.81 +/- 0.01 at fatigue (P less than 0.01). R also reached a minimum of 0.81-0.82 in each subject after 135-180 min of exercise during the carbohydrate feeding trial but increased again to 0.84-0.86 as plasma glucose rose following the carbohydrate feeding. Exercise time to fatigue was 21% longer (205 +/- 17 vs 169 +/- 12 min; P less than 0.01) during the carbohydrate ingestion trial. Plasma insulin did not increase significantly, whereas plasma free fatty acids and blood glycerol plateaued following carbohydrate ingestion. These data indicate that a single carbohydrate feeding late in exercise can supply sufficient carbohydrate to restore euglycemia and increase carbohydrate oxidation, thereby delaying fatigue. PMID- 2927303 TI - Lower vertebral bone density in male long distance runners. AB - Bone density in 13 male long distance runners (28.7 +/- 1.2 yr, 67.6 +/- 2.0 kg) and 11 male nonrunners (26.8 +/- 1.3 yr, 71.0 +/- 2.2 kg) was compared. Bone was measured at the lumbar spine and mid-tibia using dual photon absorptiometry and at the mid-radius using single photon absorptiometry. Runners (mean weekly training 92.2 +/- 6.3 km) had significantly lower (P less than 0.05) vertebral bone mineral density (1.12 +/- 0.03 g.cm-2) than nonrunners (1.24 +/- 0.04 g.cm 2). Tibial and radial bone mineral density did not differ between the groups. Daily calcium intake for runners (1,373 +/- 486 mg) and nonrunners (1,267 +/- 236 mg) exceeded the RDA. The results of this study suggest that long distance running may lead to decreased vertebral bone mineral density. The hormonal changes that occur with endurance training may contribute to this decrease. PMID- 2927304 TI - Influence of dietary iron source on measures of iron status among female runners. AB - The purpose of the present investigation was to determine whether female runners who consume a modified vegetarian diet are predisposed to iron deficiency. Two groups of female runners who were matched for age, weight, aerobic capacity, miles run per week, and number of pregnancies were obtained for this study. One group (N = 9) regularly consumed a modified vegetarian diet (MV, less than 100 g red meat.wk-1), while the other group (N = 9) consumed a diet which included red meat (RM). Serum ferritin values were significantly (P less than 0.05) lower for the MV group (X +/- SE, 7.4 +/- 1.4 ng.100 ml-1) than for the RM group (19.8 +/- 4.2 ng.100 ml-1). Total iron binding capacity (TIBC) of the serum was also significantly different between the two groups of subjects (MV, 366.5 +/- 12.2 micrograms.100 ml-1; RM, 327.2 +/- 9.6 micrograms.100 ml-1). While dietary iron intake was comparable for the two groups (MV, 14.7 +/- 2.0 mg.d-1; RM, 14.0 +/- 2.2 mg.d-1, the bioavailability of the dietary iron was significantly different (MV, 0.66 +/- 0.08 mg.d-1; RM, 0.91 +/- 0.10 mg.d-1). As the presence of heme iron (from meat, fish, and poultry) increases the bioavailability of dietary iron, the results of the present investigation suggest that vegetarian athletes have altered iron status due to the form in which their dietary iron is consumed. PMID- 2927305 TI - Ten kilometer performance and predicted velocity at VO2max among well-trained male runners. AB - Previous research (study 1) has shown that a significant relationship exists between 10 km run time (RT) and predicted running velocity at VO2max (vVO2max) among well-trained males heterogeneous in VO2max. Since competitive runners often display a homogeneous fitness profile, the purpose of this study was to determine the association between 10 km RT and vVO2max among a group of trained runners exhibiting nearly identical VO2max values (study 2). Running economy (RE), vVO2max, and velocity at a 4 mM blood lactate concentration (v at 4 mM BL) were calculated in both studies. Correlations were obtained as shown in Table 2. The relationship between VO2max and 10 km RT achieved statistical significance only in study 1, while RE explained a greater amount of performance variation in study 2. In both studies, variation in 10 km RT attributable to vVO2max was similar and exceeded that due to either VO2max or RE. vVO2max also accounted for essentially the same amount of variation in 10 km RT as did v at 4 mM BL. It was concluded that, among well-trained subjects homogeneous in VO2max, a strong relationship exists between 10 km RT and vVO2max that appears to be mediated to a large extent by RE. PMID- 2927306 TI - Specificity of limited range of motion variable resistance training. AB - The present study evaluated the effect of limited range of motion (ROM) variable resistance training on full ROM strength development. Twenty-eight men and 31 women were randomly assigned to one of the three training groups (A, B, AB) or a control group (C). A, B, and AB performed variable resistance bilateral knee extension exercise 2 (N = 25) or 3 (N = 19) d.wk-1 for 10 wk with an amount of weight that allowed one set of 7-10 repetitions. Group A trained in a ROM limited to 120 degrees to 60 degrees of knee flexion. Group B trained in a ROM limited to 60 degrees to 0 degrees of knee flexion. Group AB trained full ROM. Prior to and immediately following training, isometric knee extension strength was evaluated at 9 degrees, 20 degrees, 35 degrees, 50 degrees, 65 degrees, 80 degrees, 95 degrees, and 110 degrees of knee flexion with a Nautilus knee extension tensiometer. Reliability coefficients for repeated measurements of isometric strength at multiple joint angles were high (r = 0.86-0.95, P less than 0.01; SEE = 23.1-37.2 N.m). Compared to the control group, all training groups improved in isometric strength (P less than 0.01 at each angle tested except for group A at 9 degrees and 20 degrees of knee flexion and group B at 95 degrees of flexion. Isometric strength gains for group AB were similar throughout the full ROM. Isometric strength gains for the limited ROM trained groups were greater in the trained ROM than in the untrained ROM (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2927307 TI - Physiological responses to nine different exercise:rest protocols. AB - This study determined the metabolic responses to different exercise:rest protocols during circuit exercise using hydraulic resistance. In experiment 1, nine subjects underwent nine different 27 min exercise circuits. There were three variations of three exercise:rest protocols (2:1, 1:1, 1:2). The VO2 for the nine circuits averaged (mean +/- SEM) 1.94 +/- 0.03 l.min-1 (43% of treadmill VO2max), with the largest difference between the protocols being 13%. Heart rate averaged 152.2 +/- 3.1 beats.min-1, with the largest difference between the protocols being 8%. Increasing the exercise duration per minute or the number of exercise bouts per minute had minimal effects on the mean VO2 and heart rate response to hydraulic resistive exercise. In experiment 2, nine subjects underwent three different 9 min exercise circuits using exercise:rest protocols of 2:1, 1:1, and 1:2 while work and VO2 were simultaneously measured. Surprisingly, increases in work were not necessarily accompanied by corresponding increases in VO2. PMID- 2927308 TI - Impact of total body water fluctuations on estimation of body fat from body density. AB - The purpose was to investigate the possibility that variability in body weight in females due to water retention causes differences in body density (Db) values determined by hydrostatic weighing (HW). Determination of total body water (TBW) and Db were concurrently measured in seven females who experienced considerable fluctuations in body weight (1.5-4.5 kg) and seven males, ages 19-24. Females were measured when they felt they were at their lowest (LO) and highest (HI) body weights (BW) during a menstrual cycle. Males were randomly tested approximately 3 wk apart. Mean values of selected variables were compared in the LO vs HI testing sessions by paired t-tests. Significant mean differences were found in the females (P less than 0.01) for the following variables: BW (kg) (LO = 58.9, HI = 61.1), Db (g.cc-1) (LO = 1.0430, HI = 1.037), and percent body fat (%BF) as determined by HW alone (LO = 24.8%, HI = 27.6%). Variables significant at the P less than 0.05 level were TBW(l) (LO = 33.6, HI = 35.1) and %TBW of the fat-free body (LO = 74.5, HI = 75.9). However, changes in TBW could not entirely account for observed changes in Db. Only mean BW (kg) was significant (P less than 0.01) in the males (LO = 74.3, HI = 74.6). It is concluded that changes in TBW can in part result in significantly different Db values obtained from HW in females who did experience perceptible changes in BW during a menstrual cycle. The remaining differences may be due to changes in fat and protein content or methodological errors. PMID- 2927309 TI - Repetition blindness: the effects of stimulus modality and spatial displacement. AB - Repetition blindness (Kanwisher, 1986, 1987) is the failure to detect repetitions of words in lists presented in rapid serial visual presentation (RSVP). Two questions were investigated in the present study. First, if repetition blindness is not found with auditory presentation, it would support a specifically visual account of the effect. Second, if displacement of the two instances in visual space eliminates repetition blindness, it would suggest that repetition blindness is restricted to instances in which identical stimuli are distinguished soley by temporal differences. In Experiment 1, the subjects omitted second occurrences of repeated words in verbatim recall of rapid sentences presented visually (in RSVP), but not auditorily (using compressed speech), indicating that repetition blindness is a modality-specific phenomenon. In Experiments 2 and 3, repetition blindness was observed even when two occurrences of a written word were presented in different locations, showing that distinct locations do not guarantee token individuation. The results are discussed within a model that distinguishes between processes of type recognition and token individuation. PMID- 2927310 TI - Specific word transfer as a measure of processing in the word-superiority paradigm. AB - Explanations of context effects in the Reicher-Wheeler task and the letter identification task appeal to word-based processing, yet these tasks provide no explicit measure of word processing. An experiment is reported which was designed to investigate the use of transfer in the word-identification task as a measure of word-based processing in letter-identification tasks. It was found that encoding manipulations that determined whether a word-superiority effect was or was not found in a letter-identification task (e.g., Thompson & Massaro, 1973) also determined whether transfer was or was not found in a subsequent word identification task. The results of the experiment are discussed in terms of the utility of using transfer experiments as converging evidence about the presence and/or absence of processes that cannot be directly measured in other experimental paradigms. PMID- 2927311 TI - Phoneme monitoring and lexical processing: evidence for associative context effects. AB - In this paper, we propose a new version of the phoneme monitoring task that is well-suited for the study of lexical processing. The generalized phoneme monitoring (GPM) task, in which subjects detect target phonemes appearing anywhere in the test words, was shown to be sensitive to associative context effects. In Experiment 1, using the standard phoneme monitoring procedure in which subjects detect only word-initial targets, no effect of associative context was obtained. In contrast, clear context effects were observed in Experiment 2, which used the GPM task. Subjects responded faster to word-initial and word medial targets when the target-bearing words were preceded by an associatively related word than when preceded by an unrelated one. The differential effect of context in the two versions of the phoneme monitoring task was interpreted with reference to task demands and their role in directing selective attention. Experiment 3 showed that the size of the context effect was unaffected by the proportion of related words in the experiment, suggesting that the observed effects were not due to subject strategies. PMID- 2927312 TI - The effect of polysemy on lexical decision time: now you see it, now you don't. AB - Gernsbacher (1984) found that number of word meanings (polysemy) did not influence lexical decision time when it was operationalized as number of dictionary definitions. This finding supports her contention that subjects do not store all possible dictionary meanings for words in memory. The present experiments extended Gernsbacher's research by determining whether more psychologically valid measures of polysemy affect lexical decision time. Three metrics were used to represent the meanings that subjects actually access from memory (accessible polysemy): (1) the first meanings subjects think of when asked to define stimulus words, (2) all the meanings subjects generate for words, and (3) the average number of meanings subjects generate. The results showed that the second and third metrics of polysemy influenced lexical decision time, whereas the first metric (representing mostly the access to dominant meanings for words) only approached significance. PMID- 2927314 TI - Referential processing: reciprocity and correlates of naming and imaging. AB - To shed light on the referential processes that underlie mental translation between representations of objects and words, we studied the reciprocity and determinants of naming and imaging reaction times (RT). Ninety-six subjects pressed a key when they had covertly named 248 pictures or imaged to their names. Mean naming and imagery RTs for each item were correlated with one another, and with properties of names, images, and their interconnections suggested by prior research and dual coding theory. Imagery RTs correlated .56 (df = 246) with manual naming RTs and .58 with voicekey naming RTs from prior studies. A factor analysis of the RTs and of 31 item characteristics revealed 7 dimensions. Imagery and naming RTs loaded on a common referential factor that included variables related to both directions of processing (e.g., missing names and missing images). Naming RTs also loaded on a nonverbal-to-verbal factor that included such variables as number of different names, whereas imagery RTs loaded on a verbal-to-nonverbal factor that included such variables as rated consistency of imagery. The other factors were verbal familiarity, verbal complexity, nonverbal familiarity, and nonverbal complexity. The findings confirm the reciprocity of imaging and naming, and their relation to constructs associated with distinct phases of referential processing. PMID- 2927313 TI - A dissociative word-frequency X levels-of-processing interaction in episodic recognition and lexical decision tasks. AB - The effects of levels-of-processing and word frequency were directly compared in three different memory tests. In the episodic recognition test, the subjects decided whether or not a word or a pronounceable nonword had been previously studied. In the two lexical decision tests with either pronounceable or unpronounceable nonwords as distractors, the subjects decided whether a test item was a word or a nonword. There were four main results: (1) in all three tests, reaction times (RTs) in response to studied words were faster if they had received semantic rather than rhyme processing during study; (2) in the episodic recognition test, RTs were faster for low- than for high-frequency words; in both lexical decision tests, RTs were faster for high- than for low-frequency words, though less so when the nonword distractors were unpronounceable; (3) prior study facilitated lexical decisions more in response to low- than to high-frequency words, thereby attenuating the word-frequency effect, but more so when the nonword distractors were pronounceable; (4) in the lexical decision test with pronounceable nonword distractors, relative to prior rhyme processing, prior semantic processing facilitated performance more for high- than for low-frequency words, whereas the opposite was the case in the episodic recognition test. Discussion focused on the relationship of these results to current views of the mechanisms by which (1) word frequency and depth of processing affect performance in implicit and explicit memory tests, and (2) repetition priming attenuates word frequency effects for lexical decisions. PMID- 2927315 TI - Visual and phonological components of working memory in children. AB - Previous studies have shown that young children's immediate memory for a short series of drawings of objects is mediated by a visual component of working memory, whereas older children rely chiefly upon a phonological component. Three experiments investigated the hypothesis that older children rely also, but to a lesser extent, on visual working memory. Experiment 1 confirmed previous evidence that 11-year-olds' memory is disrupted by phonemic similarity of object names, but is unaffected by visual similarity of the objects themselves. However, when articulatory suppression was used to prevent phonological coding, levels of recall were sensitive to visual rather than phonemic similarity. Experiment 2 compared the effects of interpolating an auditory-verbal or a visual postlist task on memory for drawings viewed either with or without suppression. The visual task had a clear disruptive effect only in the suppression condition, where it interfered selectively with recall of the most recent item. Experiment 3 compared the effects of interpolating an auditory-verbal or a mixed-modality (visual auditory) postlist task when subjects were not required to suppress. There was greater interference from the mixed-modality task, and this effect was confined to the last item presented. These experiments are taken as confirming the presence of a small but reliable contribution from visual memory in 11-year-old children's recall. As in younger children, visual working memory in 11-year-olds is sensitive to visual similarity and is responsible for a final-item visual recency effect. The results also show that older children's use of visual working memory is usually masked by the more pervasive phonological component of recall. Some implications for the structure of working memory and its development are discussed. PMID- 2927316 TI - Processing of new arguments at clause boundaries. AB - In a subject-paced reading-time study, we examined the processing of new arguments at clause boundaries. Word reading times increased with the cumulative number of new-argument nouns at clause boundaries (as well as at sentence boundaries). New-argument nouns had a greater impact at clause boundaries than at nonboundary locations. In accordance with a buffer-integrate-purge model of reading (see Jarvella, 1979), the increase of reading times at boundaries was attributed to the integration of new information from the current sentence with prior information in the text representation. The increase at nonboundary locations was attributed to the growing load of buffering the new information. Reading times at clause boundaries were influenced to a greater extent by text level integration than by such sentence-level processes as organization of words into clauses and linking of clauses within a sentence. The new contribution of this study was that it showed that clause boundaries provide an opportunity not only for sentence-level processes, but also for a text-level process, namely, the integration of text-new information with the growing text representation. PMID- 2927317 TI - The time course of sense creation. AB - In everyday conversation listeners often need to create new meanings for old words. For example, listeners must create the meaning "uniformed police officers" for the word uniforms in the utterance, "There are 20,000 uniforms in this city." For such meanings, the process of sense creation must operate to supplement ordinary sense selection. The present experiments contrast two models of the time course of these processes. The error recovery model suggests that sense creation operates only after sense selection fails. The concurrent processing model suggests that sense selection and sense creation operate simultaneously. Preempting innovations--novel terms identical in form to conventional terms, such as uniforms--provide the means to contrast the models. The experiments demonstrate that the concurrent processing model gives a more accurate description of comprehension. PMID- 2927318 TI - Transfer of conditional reasoning: effects of explanations and initial problem types. AB - Transfer of reasoning on Wason's (1966) selection task was explored in three experiments. Experiment 1 tested the effects of problem explanations and verbalization instructions on transfer from abstract or thematic problems to abstract problems. Explanations facilitated transfer only when the initial problems were abstract; verbalization did not produce transfer between problems. Experiment 2 explored the effects of problem similarity and explanations on transfer between problems. Although transfer occurred following explanations, no effect of similarity was found for thematic problems. In both of these experiments, the thematic effect (Wason & Shapiro, 1971) was observed. Experiment 3 examined the effects of explanations to abstract or thematic problems on transfer to subsequent abstract or thematic problems. Transfer of reasoning occurred from both initial problem types, particularly to problems of the same type; however, transfer occurred to a greater extent from abstract problems than from thematic problems. The results are discussed in terms of problem similarity and Cheng and Holyoak's (1985) pragmatic reasoning schema hypothesis. PMID- 2927319 TI - Sensible reasoning in two tasks: rule discovery and hypothesis evaluation. AB - The hypothesis testing skills of undergraduates were measured in two tasks: the 2 4-6 rule discovery task in which students generate and assess hypotheses, and a hypothesis evaluation task, which requires only the assessment of hypotheses. The results of Experiments 1 and 2 show that the students consistently employed a disconfirmation strategy when assessing hypotheses, but employed a counterfactual inference strategy when they also were required to generate the hypotheses. The results of Experiment 3 suggest that the selection of the hypothesis testing strategy reflected a balance between the logical requirements of the task and the desirability of possible outcomes. Taken together, the findings support a more consistent picture of human rationality across tasks, and suggest alternatives to accounts of confirmation bias. PMID- 2927320 TI - Trends in mental retardation in the 1990s. PMID- 2927321 TI - Treatment of acrophobia of an institutionalized adult with mental retardation. AB - Treatment of an institutionalized 34-year-old female with mental retardation (who may have been psychotic) for acrophobia was described. Prior to therapy her phobia had precluded her placement in an upper-level ward. Assessment and therapy took place over 6 weeks and involved 13 sessions, totalling 15 hours of graduated exposure. A further 10 hours of therapy were undertaken 7 months later due to the demands of her new setting. Eighteen-month follow-up indicated that all gains had been maintained. Unprogrammed generalization was limited. PMID- 2927322 TI - Mothers' verbal directives to delayed and nondelayed children. AB - Effects of child age and child intelligence on mothers' use of verbal directives with delayed and nondelayed children ages 2.5 to 3 years and 4.5 to 5 years were examined. Mothers used significantly more directives with 2- and 4-year-old delayed children than with 2- and 4-year-old nondelayed children. The means of mothers' directives for 2- and 4-year-old children were similar for both groups. When mothers' directive scores to nondelayed 2-year-old and delayed 4-year-old children were plotted according to the children's comparable mean lengths of utterance, mothers' directives for the delayed 4-year-old children exceeded those for the nondelayed 2-year-old children with few exceptions. PMID- 2927323 TI - Metaphors as a means of understanding staff-resident relationships. AB - Three metaphors were examined as a means of understanding staff-resident relationships in the field of mental retardation. The organic and mechanical metaphors that have dominated beliefs and attitudes in this field were reviewed and critiqued. The personal metaphor that provides an image and understanding of residents not as animals or machines but as persons was examined. The two principal aspects of the personal metaphor--agency and relationship--were presented with a view toward understanding their implications in the area of staff-resident relationships. PMID- 2927324 TI - Quality of life: its measurement and use. AB - The emerging need to view improved quality of life as an outcome measure from human service programs was described, and a Quality of Life Index was proposed that can be used as either an outcome measure or the criterion for the goodness of-fit between persons and their environments. Data were presented from 685 adult clients within Nebraska's Community Based Mental Retardation Programs demonstrating the use of this Index as both an outcome measure and a criterion of the goodness-of-fit between persons who are disabled and their environments. Administrative and programmatic uses of such data were explored, along with a number of cautions to consider when assessing a person's quality of life. PMID- 2927325 TI - Psychological services for persons with mental retardation and psychiatric impairments. AB - Key informant characterizations of services provided by psychologists to persons with mental retardation and psychiatric impairments were described. Responses indicate that informants relied most heavily upon clinical history, observation and behavior checklists, and clinical signs in rendering diagnostic judgments. Therapeutic efforts were directed to a diversity of aspects of interpersonal and social adjustment, with benefit considered to be greater for persons with mild or moderate mental retardation. PMID- 2927326 TI - Fluorescence microscopy of living cells in culture. Part B. Quantitative fluorescence microscopy--imaging and spectroscopy. PMID- 2927327 TI - The midwife's role under threat? PMID- 2927328 TI - The 'Know Your Midwife' scheme--a randomised trial of continuity of care by a team of midwives. AB - A team of four midwives provided the majority of care during pregnancy, labour and the puerperium to 503 women at low obstetric risk, over a 2-year period. Compared with standard hospital care randomly allocated to 498 women this 'Know Your Midwife' scheme was associated with greater continuity in all phases of maternity care. The scheme appeared very acceptable to women: they spent less time in the antenatal clinic, and overall, felt more satisfied, better prepared and better able to discuss problems. The scheme was characterised by less obstetric intervention particularly in respect of augmentation of labour and intrapartum analgesia; labours tended to be longer. Neonatal outcome was generally similar in the two groups but the size of the trial did not allow a precise assessment of differential effects in these terms. The 'Know Your Midwife' scheme is feasible. It should now be introduced more widely but in a way which allows continuing evaluation. PMID- 2927329 TI - Babies of HIV infected women in Edinburgh. AB - Acquired Immune Deficiency Syndrome (AIDS) was first recognised in children in 1982. This paper describes a paediatric counselling and screening clinic in Edinburgh for babies born to women who are Human Immunodeficiency Virus Positive. PMID- 2927330 TI - Who continue? A preliminary examination of data on continuation of employment in midwifery. AB - A follow-up descriptive survey of the employment practice of midwives has been undertaken in an attempt to identify factors associated with more long term midwifery practice. Existing data on Notification of Intention to Practise as a Midwife was used to follow up a cohort of midwives who qualified in 1981 and 1982 in Scotland. Midwives who were older, married and who had a higher level of education when starting their midwifery training were more likely to practice long term. The implications for the Scottish midwifery service are discussed. PMID- 2927332 TI - Medical records are a source of data for answering research questions. PMID- 2927331 TI - The relationship between maternal labour analgesia and delay in the initiation of breastfeeding in healthy neonates in the early neonatal period. AB - An Infant Breastfeeding Assessment Tool was used to assess the breastfeeding behaviour of 38 healthy, full-term newborn babies of multiparous women from birth until effective feeding was established. After data collection was completed, the babies were divided into a non-medicated group (n = 18) and an alphaprodine group (n = 20) based upon the medication profile of the mother. Inter-group differences were analysed using ANOVA and Dunnett's t-test. The dependent variables were the hours from birth to establishing effective breastfeeding and IBFAT scores at 12, 24, 36 and 48 hours after birth. The findings suggest that even small doses of the narcotic analgesic alphaprodine, when administered 1 to 3 hours prior to delivery, can delay effective feeding by several hours and in some cases, days. PMID- 2927333 TI - Half our medical future. PMID- 2927334 TI - Some phenomena of medical students' diagnostic problem-solving. AB - This paper introduces a perspective on medical problem-solving that derives from recent studies of content-related learning. Results from a study of fourth-year medical students' approaches to understanding a data base of significant facts about a patient (a problem synthesis) are presented. By analysing data collected in interviews, we obtain categories of description that portray the qualitatively different ways in which the information in diagnostic problems is handled by these students. Two major categories describe the variability in approach: 'ordering' and 'structuring'. The latter category contains elements that most clinical teachers would regard as desirable; the former represents a less satisfactory approach. We provisionally identify two diagnostic strategies within each of these categories. The perspective has implications for improving instruction and assessment. PMID- 2927335 TI - Types of problem students encountered by clinical teachers on clerkships. AB - The teachers who play the all-important role of enabling students to learn on clinical clerkships must balance the two essential skills of being a good role model and maintaining objectivity in order to identify students with a variety of problems. This study describes the findings of a survey that identifies both the type of the problems that most bother teachers and the relative frequency of those problems. Non-cognitive problems (poor interpersonal skills and non assertive, shy students) were identified by teachers as being seen at the same relative frequency but posing greater difficulty than cognitive problems (poor integration skills, disorganization, poor fund of knowledge, etc.). A variety of the types of interventions to these problems are discussed. PMID- 2927336 TI - A retrospective study of attitude change during medical education. AB - A retrospective attitude questionnaire was administered to 70 of 157 graduating seniors at the end of the medical school year. Students perceived that they became more cynical during medical education. In addition, they perceived that they were more concerned with making money, more concerned for patients, and more helpful. These findings relate to the developmental stressors of medical education as they affect the individual student. Burn-out and impairment are possible consequences; a preventive approach is advocated. PMID- 2927337 TI - A curriculum on medical ignorance. AB - The information and technology explosions in medicine have exposed the vast realm of ignorance in human biology as well as the transiency of accepted knowledge and shortcomings of instructional methods which foster rote memorization, excessive reliance on conflicting data bases, and short-answer testing. To circumvent this serious deficiency in medical education, we have initiated a multifaceted Curriculum on Medical Ignorance consisting of 'questioning' seminars and hands-on clinical and laboratory experiences. This teaching programme not only emphasizes medicine's current deficiencies and limited insight into disease processes (i.e. ignorance) but also assists students in developing attitudes and behaviours to investigate basic biologic and clinical unknowns while rendering sound everyday clinical decisions in the face of fragmentary understanding. Based on evaluative feedback over the past 3 years, participants have made substantial progress towards recognizing and dealing constructively with medical ignorance and the limitations of 'knowledge of the day', thereby preparing them for the certain uncertainty of future medical practice. PMID- 2927338 TI - What 'makes' a good doctor? AB - The relation between gender, personality, school scores, grades at medical school and eventual achievement as a medical practitioner 8 years after qualifying has been explored by path analysis in a cohort of medical students. Factor analysis of data derived from a questionnaire identified a significant factor accounting for 75% of the common variance of the professional achievement scores. Standardized path coefficients were computed to indicate the relative importance of the causal factors to postgraduate achievement. Gender played an important role at many levels. For example it was apparent that many of our women graduates were seriously disadvantaged in their professional careers. Of the school subjects, chemistry was a surprising long-term predictor of postgraduate achievement. Academic achievement during medical school training, particularly in the final year, was a significant predictor, while personality attributes made their contribution to one or other aspect of achievement at earlier stages in training but made little additional direct contribution to postgraduate performance. PMID- 2927339 TI - Do conventional and innovative medical schools recruit different students? AB - A mail questionnaire was used to survey the social and demographic characteristics, educational background, attitudinal profiles and expected career choice of 243 first-year students enrolled in three US medical schools. The aim was to determine whether different types of schools selected different types of students. Two schools were considered as conventional whereas one school was considered as innovative both in its admission policies and in its curriculum which emphasizes a biopsychosocial approach to health care. The survey achieved an 84% response rate. The results showed no difference in students' career expectations. Students recruited in the innovative school, however, differed from students recruited in the conventional schools with regard to their social and demographic characteristics, educational background and attitudinal profiles. This study suggests that as some medical schools are innovating in their curriculum and admission policies, new types of medical students are entering medicine. Implications of these results are discussed. PMID- 2927340 TI - Student population changes and progress in Belgian medical schools. AB - The present study was designed to analyse the evolution of student populations- undergraduates and graduates--in the 11 Belgian medical schools from 1969 to 1982. During this period, an overall 44% drop in the number of entrants was observed, while the number of medical graduates continued to rise until 1977, when it stabilized. French- and Flemish-speaking universities followed a similar trend. During the period under study, the proportion of women students virtually doubled from 25 to 44%. The total success rate averaged 39% for Belgian students and 24% for foreigners. By comparing success curves over the years, the various medical faculties were rated with a 'selectivity' score, indicating those significantly different from the national average. A separate classification was made for preclinical (3 years of 'Candidature') and clinical (4 years of 'Doctorat') phases since, among the 11 Belgian medical schools, four teach only preclinical subjects. Marked differences in failure rates were observed between candidature and doctoral education even within universities. PMID- 2927341 TI - Medical education and economics. AB - The time available to medical students for learning is scarce in relation to the knowledge they are asked to absorb. New material should not therefore be added to medical curricula without careful consideration of the benefits of the extra knowledge compared to the costs of obtaining this knowledge. In this paper a justification for integrating economic principles into medical education is presented. It would benefit society by encouraging the practice of efficient medicine, and benefit students by giving them the ability to absorb the growing economic content of the medical literature and by encouraging an appreciation of why economic factors will influence their clinical decision-making. These benefits would accrue at little cost because only a limited number of economic concepts need to be absorbed by medical students. The critical concepts are outlined and some of the obstacles to students applying this knowledge in practice are considered. The paper concludes by suggesting that the impact of teaching economics to medical students should be evaluated, but this will require further research into ways of evaluating the outcome of medical education programmes in general. PMID- 2927342 TI - The curriculum of communication skills teaching at Maastricht Medical School. AB - In the Skillslab at Maastricht Medical School students are prepared for their first encounters with patients. Students can focus on individual skills, separately mastering each skill in a controlled systematic manner. With this foundation students are better equipped to face the complex intellectual and emotional demands of real patients. A large proportion of training concerns communication skills. Features of Skillslab communication skills training programme are: (1) its continuity (once every 2 weeks, from year 1 to year 6); (2) a gradual increase of complexity in skills (basic interview skills, phases of interviews, entire interviews, problem patients); (3) a gradual increase of complexity in practice situations (apparatus, role-playing, simulated patients, real patients). Evaluation shows students' and teachers' satisfaction with the programme. Comparison with conditions required for interpersonal skills training shows that these are fully met. However, there are drawbacks, which are described. PMID- 2927343 TI - Doctors qualifying from United Kingdom medical schools during the calendar years 1977 and 1983. AB - At the conclusion of undergraduate medical education in the United Kingdom most students pass a university qualifying examination and obtain a degree in medicine and surgery. Some students pass an external non-university qualifying examination in medicine as an alternative to obtaining a degree, and some do both. The degree may be obtained in the same year as the non-university qualifying examination, or in a different year. Some students from a medical school intake qualify in a later year than expected, for various reasons. Data from university, Health Department and other sources may relate to the academic year, the calendar year, or a fixed date such as 30 September. It is not a simple exercise, therefore, to define the exact number of people who qualify to practise medicine, for the first time, in any given 'year'. In counting qualifiers from individual medical schools, the problems are further compounded by the movement of students between the preclinical and clinical stages of the course, particularly from Oxford and Cambridge to London teaching hospitals. This paper analyses the situation for the calendar years 1977 and 1983, showing a decline in the number of students obtaining double (i.e. both university and non-university) qualifications. The number of UK graduates not registering with the General Medical Council to practise, at least for a time, in the UK was small, and the population base compiled for Medical Career Research Group studies was reasonably accurate in each of the 2 years examined. PMID- 2927345 TI - A survey of preclinical psychology teaching in United kingdom medical schools. AB - This paper is based on a relatively brief postal survey of teaching in United Kingdom medical schools. Data were collected from 29 of the 30 medical schools about the provisions for their preclinical psychology teaching and examination as well as some indicators of the reactions of students and other staff. The results show that some progress has been made in the teaching of psychology to medical students but there is considerable variation across schools. The rated level of interest and attendance by students appears to be good and the rated attitudes of other staff were mixed. However, many of the respondents reported that their teaching hours were not adequate and that they wanted to achieve other changes in their type and content of teaching. PMID- 2927344 TI - Learning the educator role: a course for medical students. AB - The design and evaluation of a revised course on educational skills for medical students is described. The overall aim of this elective was to help students develop a working concept of their educator role regarding themselves, their peers, and their patients. The programme comprised 15 2-hour weekly meetings consisting of small-group discussion and exercises around issues of self-learning skills, peer teaching, and the process of patient education. Advanced preparation was promoted by readings and special assignments. Self-assessment, peer assessment, and continuous assessment based on course-work were used to help student learning and to provide a basis for final grading. During a 3-year study period, the Course Valuing Inventory (CVI) and a goal-oriented questionnaire were used for course evaluation. Evaluation done on five consecutive classes showed favourable indices of course attractiveness. It also showed broad progress of most students in the course goals and high positive CVI scores for cognitive, personal and behavioural learnings, in addition to course valuing. Students' perceptions of improvement in self-appraisal, communication skills and personal growth were related findings. Significant, moderate correlations were found between CVI learning scores and both the self-ratings of progress in the course goals and of attitude towards the educator role. Reinforcement of the positive attitude towards this role was a valuable finding related to a lasting effect: a significant increase in the choice of undergraduate preceptorships by the participants when compared to the control sample of students not exposed to this learning experience. PMID- 2927346 TI - Medical students' attitudes to old people and career preference: the case of Nottingham Medical School. AB - Medical students' attitudes to the elderly population were compared at entry to and exit from a month-long clinical attachment in the Department of Health Care of the Elderly at Nottingham University. The study investigated clinical students for the 1983-4 and 1986-7 academic years using a questionnaire employing a Rosencranz-McNevin semantic differential scale to measure general attitudes to old age and a Likert scale to measure attitudes to medical care. A question was also asked about career preferences. Improvements in attitudes during the month were noted for both cohort groups, but different trends for the two groups are discussed in the context of the growing pre-clinical effects of such a specialist department in a medical school. PMID- 2927347 TI - A community-based learning experience for medical students. AB - A programme in which medical students are attached to Children's Institutions for one year is described. The students' role embraces a medical and psychosocial component in which students conduct clinics, screening programmes and health education as well as develop relationships with individuals and groups of children. This experiential learning programme enables medical students to obtain an understanding of children's needs and work through their own feelings which are aroused when confronted with children who have been deprived and abused. PMID- 2927348 TI - Disaster, stress and the doctor. AB - Man is unable to control for the ever-present potential of disaster. In the past practices and procedures have been developed to minimize physical risk and maximize personal safety. However, there has been little awareness of, or attention to, the stress to those involved in the care-giving process to the victims. Medical care-givers are at the forefront of post-disaster intervention. It is necessary to provide training and support for doctors engaged in post disaster work, especially with regard to the psychosocial consequences for patients, relatives, and the medical team as a group and as individuals. Pre disaster preparation is suggested as a situational moderator in the prevention or management of extreme strain in medical and paramedical staff. Specifically, social support in the form of team-building and supervisory support and debriefing, use of personality hardiness concepts in selection and training of staff, and general emergency preparedness should form part of a disaster preparation plan. Medical social workers and psychologists can play an important role as facilitators in disaster preparation. The importance of education and increasing awareness of disaster effects on the health team is emphasized. PMID- 2927349 TI - A written test as an alternative to performance testing. AB - Performance tests are logistically complex and time consuming. To reach adequate reliability long tests are imperative. Additionally, they are very difficult to adapt to the individual learning paths of students, which is necessary in problem based learning. This study investigates a written alternative to performance based tests. A Knowledge Test of Skills (KTS) was developed and administered to 380 subjects of various educational levels, including both first-year students and recently graduated doctors. By comparing KTS scores with scores on performance tests strong convergent validity was demonstrated. The KTS failed discriminant validity when compared with a general medical knowledge test. Also the identification of sub-tests discriminating between behavioural and cognitive aspects was not successful. This was due to the interdependence of the constructs measured. The KTS was able to demonstrate differences in ability level and showed subtle changes in response patterns over items, indicating construct validity. It was concluded that the KTS is a valid instrument for predicting performance scores and could very well be applied as supplementary information to performance testing. The relative ease of construction and efficiency makes the KTS a suitable substitute instrument for research purposes. The study also showed that in higher ability levels the concepts which were meant to be measured were highly related, giving evidence to the general factor theory of competence. However, it appeared that this general factor was originally non-existent in first-year students and that these competencies integrate as the educational process develops. PMID- 2927350 TI - Malignancy may contribute to rapid evolution. AB - Characteristics of malignant tumors, including anaerobic metabolism and metastases to lung, liver, bone and brain, may permit the enhanced survival of edited parts of the genome during periods of rapid environmental change. Carcinogenesis may be partially analogous to fossilization. PMID- 2927351 TI - Lung cancer, the motor vehicle and its subtle influence on body functions. AB - It is suggested that according to experimental evidence, the stimulation of automatic body functions by travelling in motor vehicles leads to the development of lung cancer. The data available for Australia during the period 1940 to 1984 also shows that the difference between male and female lung cancer rates may be explained by exposure to travel. PMID- 2927352 TI - An integrated neuropathophysiological model of schizophrenia. AB - Schizophrenia is a disease of consciousness. The different neuroscientific disciplines have reported correlations with dysfunction and pathology at various levels in the hierarchy of biological explanation. A holistic model of schizophrenia is presented, developed from the premise that the neurophysiological correlate of consciousness is the cortical electrical interference pattern produced by the superimposition of the sensory event related potential on the basal alpha rhythm. The role of the Isodendritic Core of the Brain is discussed and the genesis of schizophrenic symptoms is related to post mortem histopathological findings that can be attributed to viral induced fibrillary gliosis. PMID- 2927353 TI - Cholesterol and cancer: comparative biochemistry and selective toxicity. AB - There is abundant evidence in the literature for the existence of a difference between normal and neoplastic cells with regard to the regulation of cholesterol biosynthesis. More specifically, the loss of negative feedback control of this pathway seems to be a property of transformed cells. Herein we describe the relationship between cholesterol and cancer, and we describe a model which attempts to employ Adrien Albert's second principle of selectivity--that of comparative biochemistry--by exploiting the above mentioned difference in regulation. PMID- 2927354 TI - A proposal for the development of clonal hemopoietic leukemias. AB - We elaborate on the pathogenesis of (human) hemopoietic leukemias according to a model whereby malignant growth follows the anachronistic expression of gene P in a rare cell at a certain stage of differentiation (1,2). P is a stimulus needed for renewal of hemopoietic cells. When illegally autocatalytic for P any mitotically competent cell (not necessarily pluripotent, at least originally) acquires the marginal (seldom complete) autonomous growth of malignant cells. Rather than confrontational, these views complement advantageously the mutation model and account for certain peculiarities of (human) leukemic cells, such as the propensity to differentiate terminally when isolated from their in vivo microenvironments. In addition, we discuss the rare occurrence of certain human leukemias (e.g., erythroleukemias and polycythemia veras) comparatively to the surprisingly more frequent chronic and acute myelogenous leukemias. This occurs in spite of the similarity between erythroid and myeloid populations in terms of size (mass of cells) and number of targets at mutational risk. Thus the classic mutation model predicts that random hits, after radiation exposure for example, should induce erythroid and myeloid leukemias with similar frequencies in contrast to clinical findings (3) and the predictions from our model. PMID- 2927355 TI - Primary constipation: an underlying mechanism. AB - Primary (simple) constipation is a consequence of habitual bowel elimination on common toilet seats. A considerable proportion of the population with normal bowel movement frequency has difficulty emptying their bowels, the principal cause of which is the obstructive nature of the recto-anal angle and its association with the sitting posture normally used in defecation. The only natural defecation posture for a human being is squatting. The alignment of the recto-anal angle associated with squatting permits smooth bowel elimination. This prevents excessive straining with the potential for resultant damage to the recto anal region and, possibly, to the colon and other organs. There is no evidence that habitual bowel elimination at a given time each day contributes considerably to the final act of rectal emptying. The natural behavior to empty the bowels in response to a strong defecation reflex alleviates bowel emptying by means of the recto anal inhibitory reflex. PMID- 2927356 TI - Tomatoes and Parkinson's disease. AB - Recent developments have focused attention on the possibility that a toxic environmental factor may be the cause of Parkinson's disease (PD). A hypothesis seeking to explain the cause of PD must explain its worldwide distribution, the small percentage of the population affected, geographic variations in prevalence and why PD was unrecognized prior to the early nineteenth century. The difficulties in finding a ubiquitous environmental agent which could account for these observations, may be illustrated by considering the hypothesis that such an agent may be a constituent of a common plant such as the tomato. This hypothesis meets all the necessary prerequisites. It is testable and appears to be an excellent starting point from which to search for the cause of PD. PMID- 2927357 TI - The hypervitaminosis-A rat: a model for mucin hypersecretion in cystic fibrosis? AB - Cystic fibrosis is a devastating disease with pathognomonic features typically displayed in the exocrine system. An obvious drawback with human clinical studies of the disease is the relative inaccessibility of its "target-tissues," i.e., the salivary glands, intestine, pancreas, and tracheobronchial tree. Thus, little is known about its underlying cellular mechanisms. For this reason, physiologically relevant animal models for the disease are vitally needed. At present, there are animal models available for certain salivary gland biochemical aspects of the disease and for bicarbonate ion secretory alterations. However, no adequate model exists for excessive mucus production, an aspect of the disease which sets the stage for life-threatening infections and digestive disorders. This manuscript examines morphological and biochemical changes occurring in various biological systems exposed to high levels of vitamin A and correlates such changes with abnormalities commonly seen in cystic fibrosis. PMID- 2927358 TI - Possible role of adsorbed surfactant in controlling membrane permeability and function. AB - It is well established in the physical sciences that the adsorption of a monolayer of certain surfactants onto the surface of a synthetic membrane used for ultrafiltration can greatly modify its permeability to water and its ability to transmit small solute molecules and ions of physiological interest. In this hypothesis, it is proposed that, when indigenous surfactant is adsorbed to certain membranes in the body, it can similarly modify their permeability. Since adsorption can be a rapidly reversible process, this would provide a simple physical means of controlling the overall level of physiological activity of the membrane and, possibly, an additional means of differentiating membranes according to function. The hypothesis raises many questions concerning its applicability to the general structure of biological membranes, the nature of the surfactant, its ability to adsorb to solid surfaces and the reasons why such a coating may have been missed. There are then the questions of which membranes might benefit most and what happens if the coating is too sparse or is removed unintentionally. PMID- 2927359 TI - Reproductive events, occurring in adolescence at the time of development of reproductive organs and at the time of tumour initiation, have a bearing on growth characteristics and reproductive hormone regulation in normal and tumour tissue investigated decades later--a hypothesis. AB - Both animal and human data indicate that reproductive events taking place early in reproductive life may have an important influence on growth characteristics and reproductive hormone regulation in both normal tissue and neoplastic tissue investigated later in life. PMID- 2927360 TI - The medical examiner and the press. PMID- 2927361 TI - Drugs for hypertension. PMID- 2927362 TI - Drugs for hypertensive emergencies. PMID- 2927363 TI - Thoughts about medical writing, editing, and publishing. PMID- 2927364 TI - The power of simple words. Interview by Richard L. Reece. PMID- 2927365 TI - Thunder on the right. Interview by Richard L. Reece. PMID- 2927366 TI - Outcome data. PMID- 2927367 TI - Where medicine and media clash. PMID- 2927368 TI - Are doctors computer-compatible? Are computers physician-friendly? PMID- 2927369 TI - MDs prefer books, despite hike in on-line data. PMID- 2927370 TI - Practice what you preach! PMID- 2927372 TI - HIV-infected needles. PMID- 2927371 TI - The Minnesota Board of Medical Examiners. A report of the Minnesota Medical Association Committee on Ethics and Medical-Legal Affairs. PMID- 2927373 TI - Incidence of malnutrition in patients with acquired immunodeficiency syndrome. PMID- 2927374 TI - In search of the "preferred fuel". PMID- 2927375 TI - Nurse Education Today--1989. PMID- 2927376 TI - Changing times changing paradigm (1): From hospital training and college education in Australia. AB - In 1985, nurse education in New South Wales (NSW), Australia changed from hospital based nursing courses to preparation for comprehensive registration within the tertiary sector. The Nightingale apprenticeship system with an emphasis on the service needs of the institution had persisted for almost a century. The early 1970's however saw the emergence in Australia of a new paradigm in nurse education challenging the traditional training perspective. The student nurse in NSW has now assumed the role of learner and is supernumerary to the health care team when practising in a wide range of health care settings. This article has two parts, the first of which discusses the background to the development of a new paradigm in nurse education and the implications of the change process. In particular, the reaction of the medical profession to the greater degree of autonomy demonstrated by nurses in relation to their preparation for practice, is discussed. PMID- 2927377 TI - Accreditation of nursing programs--issues raised by formalising accountability in nursing education. AB - As nurses professionalise, the drive to be seen as accountable intensifies. Formalising accountability has certain dangers which are examined in this paper. The claims for accountability through accreditation processes in three areas- hospital administration, general post secondary institutions and nursing--are considered and questions raised in each. The fact that the move is not unique to nursing, nor is it new, allows for an indepth analysis of the thinking surrounding formalised accountability and for exploration of the issues nurses can debate when initiating such procedures. PMID- 2927378 TI - Progression from enrolled to registered general nurse (1): Charting the conversion. AB - This is a report of part of an empirical evaluation of a conversion course for Enrolled Nurses. The focus of the study was the changes, if any, which might take place in the students. A five faceted approach was used to collect data including three value exercises designed to identify those characteristics and values deemed by the Nurse to be important elements of his/her self image, diary keeping and meetings with the students. This part of the paper deals with the methodological aspects of the study and reports on the diary keeping and the meetings with the students. Part two will relate to the value exercises used. The study provides evidence of some of the difficulties experienced by students in the transition from Enrolled Nurse to Registered General Nurse status. It also provides evidence of 'desirable' changes in the students which occurred during the course. PMID- 2927379 TI - Student assessment in basic nursing education in Scotland. AB - This paper presents some of the findings of a 4-year-study of the examination system for student nurses entering basic nursing courses offered by all Colleges of Nursing and Midwifery in Scotland. These modular courses, first implemented in 1982, involve students in a series of internal (college) assessments and two external (national) examinations. Results for 2742 students on 16,764 written assessments were analysed. The hypotheses that there would be high correlation between different modular results in internal assessments, and between results in internal assessments and external examinations were not supported. Implications for possible changes in the examination system are discussed. PMID- 2927380 TI - Traditional or systematic nursing? An evaluation of the written curricula of registered and enrolled nurses in Finland. AB - In order to develop the professional identity of registered nurses (RNs) and enrolled nurses (ENs), it is essential that the core of the written curricula be based on nursing science. In this study, content analysis was used to examine how theoretically-developed elements of nursing education were taken into consideration in the curricula (one local and one nationwide curriculum were analysed). The research questions were: 1. to what extent do the characteristics of either traditional or of systematic nursing appear in the educational objectives of nursing education? 2. to what extent do the characteristics of systematic nursing appear in the curricula, and as distinct elements in the objectives of nursing education? The written nursing curricula which were analysed seem to be characterised by traditional nursing, while features of systematic nursing appear as minor elements only. PMID- 2927381 TI - Exploring nurse educators' views of experiential learning: a pilot study. AB - The 1982 syllabus of training for psychiatric nurse students recommended the use of experiential learning methods. This paper describes a pilot study aimed at identifying nurse educator's views of experiential learning. Twelve nurse educators were interviewed and the method of content analysis was used to interpret the data emerging out of the transcripts of those interviews. Various features were noted including: opinions over how 'experiential learning' was to be defined; the fact that many educators feel that students find experiential learning methods uncomfortable or threatening, and difficulty in evaluating experiential learning activities. The findings, although tentative, may have implications for the future training of nurse educators and for the future planning and practice of experiential learning in nurse education. PMID- 2927382 TI - Using an alternative model to design a registered general nurse curriculum. AB - This paper suggests that in view of the recent changes in nurse education an alternative to the behavioural objectives model may need to be considered for designing a Registered General Nurse curriculum. The Foundation Module of a programme is used as an example to show that a process approach could be an appropriate alternative. PMID- 2927383 TI - Models of training. AB - This article describes a framework for looking at the implications of requests for training. It asks whether the most appropriate staff are being sent on courses and what plans have been made to integrate the lessons from the training back into the workplace. PMID- 2927384 TI - Social skills training: some ideas on its origin, nature and application. AB - This paper stems out of my current involvement in the Teaching of Social Skills training to health professionals mainly concerned with mental health. It is hoped this paper will stimulate exchange of ideas and experiences amongst health professionals, particularly other teachers and practitioners in mental health. The paper starts with a historical overview (antecedent conditions) highlighting some early views, early successes and failures in the areas of psychological intervention. The advent and purpose of Social Skills training is then presented in the light of these early experiences. The work of a notable British Social Psychologist (Michael Argyle) and his colleagues is selected to achieve two purposes: 1. to describe a range of, personal and interpersonal skills now considered under social skills training, 2. to demonstrate how all these social skills may be taught or learned using key elements of one model. The paper also briefly addresses some ostensive similarities between social skills and motor skills as depicted in the key elements of this one model. It finishes by offering a summary of the model's application plus some hints on training techniques. PMID- 2927385 TI - General recommendations on immunization. PMID- 2927386 TI - Corticosterone increases protein tyrosine kinase activity in the locus coeruleus and other monoaminergic nuclei of rat brain. AB - Protein tyrosine kinase was studied as a possible target of glucocorticoid action in discrete regions of rat brain. It was found that 7 days of corticosterone treatment produced a 20-25% increase in protein tyrosine kinase activity specifically in three monoaminergic nuclei known to be regulated by glucocorticoids in vivo. Thus, corticosterone increased enzyme activity in the locus coeruleus (LC), dorsal raphe, and ventral tegmentum, but not in a number of other brain regions studied. This phenomenon was characterized further in the LC. Bilateral adrenalectomy was shown to decrease protein tyrosine kinase levels in this brain region, an effect reversed completely by corticosterone replacement, indicating that this adrenal steroid plays a role in maintaining levels of the enzyme under physiological conditions in vivo. Chronic corticosterone was also found to increase levels of immunoreactivity of c-src, a well characterized protein tyrosine kinase, in the LC, results indicating that corticosterone increases protein tyrosine kinase activity in this brain region at least in part by increasing the total amount of this enzyme. Immunoblotting analysis of LC extracts with antibodies specific for phosphotyrosine indicated that the corticosterone-induced increased in protein tyrosine kinase activity in the LC is associated with a 60% increase in the incorporation of phosphotyrosine into endogenous proteins. The results demonstrate that protein tyrosine kinase activity is regulated by glucocorticoids in discrete regions of the central nervous system and raise the possibility that regulation of these brain regions by glucocorticoids is mediated in part through effects on this enzyme. PMID- 2927387 TI - Ketanserin reduces a particular monoamine pool in peripheral tissues. AB - The effect of ketanserin and tetrabenazine treatment on monoamine and metabolite levels in central and peripheral tissues was investigated in young and senescent male Wistar and spontaneously hypertensive Okamota rats. Control animals showed significantly higher brain monoamine levels and 3 and 5.5 times higher dopamine levels in the vas deferens of the senescent and hypertensive rats, as compared with young normotensive rats. Ketanserin (20 mg/kg) produced an average of 20% reduction of brain monoamines without changing metabolite levels. In the vas deferens, dopamine was reduced by 85% and norepinephrine by 30%. In cardiovascular tissues, norepinephrine was 40% to 50% decreased and in the spleen norepinephrine was 60% and 5-hydroxytryptamine 30% reduced. Ketanserin (5 mg/kg) had only a marked effect on dopamine in the vas deferens and on norepinephrine in the portal vein. Tetrabenazine at 20 mg/kg produced complete depletion of the monoamine and 3-methoxytyramine levels in the brain with a concomitant rise in acid metabolites. In peripheral tissues, amine levels were reduced by 55% to 80%; dopamine in the vas deferens was 93% decreased. Tetrabenazine (5 mg/kg) still had marked effects in all tissues. The drug effects were the same in the three types of rats and the effects did not markedly change with chronic treatment up to 20 days. It is hypothesized that at least two different mechanisms are involved in monoamine depletion, 1) the classically proposed inhibition of uptake of monoamines in the storage vesicles, a property of tetrabenazine not shared by ketanserin in vivo and 2) triggering of the release of monoamines from a ketanserin-sensitive pool, which is relatively more important in peripheral tissues than in the brain. The latter process is probably mediated by previously identified ketanserin-binding release sites on nerve terminals and platelets. The ketanserin-sensitive monoamine pools in peripheral tissues may have a role in cardiovascular pathologies. PMID- 2927388 TI - Molecular detection of chromosomal translocations that disrupt the putative retinoblastoma susceptibility locus. AB - A candidate DNA sequence with many of the properties predicted for the retinoblastoma susceptibility (RB1) locus has been cloned (S. H. Friend, R. Bernards, S. Rogelj, R. A. Weinberg, J. M. Rapaport, D. M. Albert, and T. P. Dryja, Nature [London] 323:643-645, 1986). The large size of this gene (ca. 200 kilobases [kb]) and its multiple dispersed exons (Wiggs et al., N. Engl. J. Med. 318:151-157, 1988) complicate molecular screening strategies important in prenatal and presymptomatic diagnosis and in carrier detection. Here we used field inversion gel electrophoresis (FIGE) to construct a restriction map of approximately 1,000 kb of DNA surrounding the RB1 locus and to detect the translocation breakpoints in three retinoblastoma patients. DNA probes from either the 5' or 3' end of the gene were used to detect a 250-kb EagI restriction fragment in DNA from unaffected individuals. Both probes identified an additional hybridizing fragment in the DNA from each patient, permitting the breakpoints in all three to be mapped within the cloned RB1 gene. Analysis of the breakpoint in one translocation cell line allowed the RB1 gene to be oriented with its 5' end toward the centromere. The 5' end of the gene also appeared to be associated with a clustering of sites for several infrequently cleaving restriction enzymes, indicating the presence of an HpaII tiny fragment island. The detection and mapping of the translocation breakpoints of all three retinoblastoma patients to within the putative RB1 gene substantiated the authenticity of this candidate sequence and demonstrated the utility of FIGE in detecting chromosomal rearrangements affecting this locus. PMID- 2927390 TI - Replication of DNA minicircles in kinetoplasts isolated from Crithidia fasciculata: structure of nascent minicircles. AB - We have previously described an isolated kinetoplast system from Crithidia fasciculata capable of ATP-dependent replication of kinetoplast DNA minicircles (L. Birkenmeyer and D.S. Ray, J. Biol. Chem. 261: 2362-2368, 1986). We present here the identification of two new minicircle species observed in short pulse labeling experiments in this system. The earliest labeled minicircle species (component A) contains both nascent H and L strands and is heterogeneous in sedimentation and electrophoretic migration. Component A has characteristics consistent with a Cairns-type structure in which the L strand is the leading strand and the H strand is the lagging strand. The other new species (component B) has a nascent 2.5-kilobase linear L strand with a single discontinuity that mapped to either of two alternative origins located 180 degrees apart on the minicircle map. Component B could be repaired to a covalently closed form by Escherichia coli polymerase I and T4 ligase but not by T4 polymerase and T4 ligase. Even though component B has a single gap in one strand, it had an electrophoretic mobility on an agarose gel (minus ethidium bromide) similar to that of a supercoiled circle with three supertwists. Treatment of component B with topoisomerase II converted it to a form that comigrated with a nicked open circular form (replicative form II). These results indicate that component B is a knotted topoisomer of a kinetoplast DNA minicircle with a single gap in the L strand. PMID- 2927389 TI - Construction and properties of replication-competent murine retroviral vectors encoding methotrexate resistance. AB - A series of replication-competent Moloney murine leukemia virus vectors was constructed in which each vector contained a mutant dihydrofolate reductase (DHFR) cDNA insert in the U3 region of the viral long terminal repeat. Two of the resulting viruses, MLV (murine leukemia virus) DHFR*-5 and MLV DHFR*-7, were able to stably transfer methotrexate resistance to infected fibroblast cells upon multiple rounds of virus replication and in the absence of drug selection. Cell lines producing recombinant virus with high titers were established, which indicated that the insert did not grossly interfere with viral replication functions. These vectors should be useful for introducing and expressing foreign genes in vivo in tissues and whole animals in which virus spread is needed for efficient infection. PMID- 2927391 TI - Spontaneous germ line virus infection and retroviral insertional mutagenesis in eighteen transgenic Srev lines of mice. AB - SWR/J-RF/J hybrid mice spontaneously acquire new germ line ecotropic proviruses at high frequency. In the studies described here, we used these hybrids to produce 18 transgenic mouse lines, each carrying a single newly acquired Srev locus (SWR/J-RF/J ecotropic proviral locus). All of the newly acquired proviruses identified in mosaic founder SWR/J-RF/J mice that could be transmitted through the germ line were also present in somatic tissues, demonstrating that viral integration occurred before the germ line was set aside from the somatic lineages. Quantitative analysis of proviral DNA copy numbers in somatic and germinal tissues of mosaic founder parents combined with structural analysis of Srev loci indicated that these proviruses are acquired after multiple rounds of somatic viral reinfection and that most of these viral integration events occurred after DNA replication in the zygote and before DNA replication in the four-cell embryo. The frequency of provirus acquisition in Srev lines that expressed the infectious ecotropic virus was similar to that in SWR.RF mice carrying Emv-16 and Emv-17, suggesting that the chromosomal integration site of the parental locus is not an important determinant for high-frequency provirus acquisition. The frequency of recessive lethal mutations induced by spontaneous viral integration was 5%, which was similar to that induced by preimplantation embryo infection. This approach represents a simple and viable strategy for inducing and studying mutations that affect mammalian development. PMID- 2927393 TI - Molecular and biochemical characterization of the human trk proto-oncogene. AB - Molecular analysis of the human trk oncogene, a transforming gene isolated from a colon carcinoma biopsy, revealed the existence of a novel member of the tyrosine kinase gene family. This locus, which we now designate the trk proto-oncogene, codes for a protein of 790 amino acid residues that has several features characteristic of cell surface receptors. They include (i) a 32-amino-acid-long putative signal peptide, (ii) an amino-terminal moiety (residues 33 to 407) rich in consensus sites for N-glycosylation, (iii) a transmembrane domain, (iv) a kinase catalytic region highly related to that of other tyrosine kinases, and (v) a very short (15 residue) carboxy-terminal tail. Residues 1 to 392 were absent in the trk oncogene, as they were replaced by tropomyosin sequences. However, no other differences were found between the transforming and nontransforming trk alleles (residues 392 to 790), suggesting that no additional mutations are required to activate the transforming potential of this gene. The human trk proto oncogene codes for a 140,000-dalton glycoprotein, designated gp140proto-trk. However, its primary translational product is a 110,000-dalton glycoprotein which becomes immediately glycosylated, presumably during its translocation into the endoplasmic reticulum. This molecule, designated gp110proto-trk, is further glycosylated to yield the mature form, gp140proto-trk. Both gp110proto-trk and gp140proto-trk proteins possess in vitro kinase activity specific for tyrosine residues. Finally, iodination of intact NIH 3T3 cells expressing trk proto oncogene products indicated that only the mature form, gp140proto-trk, cross the plasma membrane, becoming exposed to the outside of the cell. These results indicate that the product of the human trk locus is a novel tyrosine kinase cell surface receptor for an as yet unknown ligand. PMID- 2927392 TI - Isolation and characterization of related cDNA clones encoding skeletal muscle beta-tropomyosin and a low-molecular-weight nonmuscle tropomyosin isoform. AB - We have isolated and characterized cDNA clones from chicken cDNA libraries derived from skeletal muscle, body wall, and cultured fibroblasts. A clone isolated from a skeletal muscle cDNA library contains the complete protein-coding sequence of the 284-amino-acid skeletal muscle beta-tropomyosin together with 72 bases of 5' untranslated sequence and nearly the entire 3' untranslated region (about 660 bases), lacking only the last 4 bases and the poly(A) tail. A second clone, isolated from the fibroblast cDNA library, contains the complete protein coding sequence of a 248-amino-acid fibroblast tropomyosin together with 77 bases of 5' untranslated sequence and 235 bases of 3' untranslated sequence through the poly(A) tract. The derived amino acid sequence from this clone exhibits only 82% homology with rat fibroblast tropomyosin 4 and 80% homology with human fibroblast tropomyosin TM30nm, indicating that this clone encodes a third 248-amino-acid tropomyosin isoform class. The protein product of this mRNA is fibroblast tropomyosin 3b, one of two low-molecular-weight isoforms expressed in chicken fibroblast cultures. Comparing the sequences of the skeletal muscle and fibroblast cDNAs with a previously characterized clone which encodes the smooth muscle alpha-tropomyosin reveals two regions of absolute homology, suggesting that these three clones were derived from the same gene by alternative RNA splicing. PMID- 2927394 TI - Electron microscopy reveals that transcription factor TFIIIA bends 5S DNA. AB - We have used a high-resolution analytical electron microscopic technique, electron spectroscopic imaging, to study the in vitro interaction between the transcription factor IIIA (TFIIIA) and 5S ribosomal gene DNA. The images and analytical measurements support our proposal that the helix axis is bent by the protein into a hairpin-shaped configuration. PMID- 2927395 TI - An overhanging 3' terminus is a conserved feature of telomeres. AB - The reactivity of single-stranded thymidines with osmium tetraoxide was used to demonstrate the existence of a terminal overhang of the G-rich strand of telomeres from two distantly related eucaryotes, the ciliated protozoan Tetrahymena spp. and the acellular slime mold Didymium spp. Conservation of a G strand overhang at the molecular terminus of telomeres is consistent with our suggestion that an unusual DNA structure formed by the G-strand overhang is important for telomere function (E. Henderson, C. C. Hardin, S. K. Wolk, I. Tinoco Jr., and E. H. Blackburn, Cell 51:899-908, 1987). PMID- 2927396 TI - Structural determinant of the species-specific transcription of the mouse rRNA gene promoter. AB - Mammalian ribosomal DNA (rDNA) transcription has a certain species specificity such that, both in vivo and in vitro, human rDNA cannot be transcribed by mouse machinery and vice versa. This is due to a species-dependent transcription factor, TFID (Y. Mishima, I. Financsek, R. Kominami, and M. Muramatsu, Nucleic Acids Res. 10:6659-6670, 1982). On the basis of the information obtained from 5' and 3' substitution mutants, we prepared a chimeric gene in which the mouse sequence from positions -32 to -14 was inserted into the corresponding location of the human rDNA promoter. The chimeric gene could be transcribed by mouse extracts nearly as efficiently as the wild-type mouse promoter. The chimeric gene could also sequester transcription factor TFID at an efficiency similar to that for the mouse promoter. Partially purified mouse TFID that could not protect the human rDNA promoter against DNase I produced a clear footprint on this chimeric gene that was similar to that on mouse rDNA promoter. The basic structure of the mouse rDNA core promoter is discussed in relation to the interaction with TFID. PMID- 2927397 TI - Specific binding of estrogen receptor to the estrogen response element. AB - Gene transfer studies have shown that estrogen regulation of specific genes is mediated by estrogen response elements (ERE). We report that binding of the estrogen receptor to the ERE can be detected by a gel retardation (band shift) assay. This binding interaction was highly sequence and receptor specific. Methylation interference analysis showed that the ERE contact sites of estrogen receptor displayed a perfect twofold rotational symmetry. This is compatible with estrogen receptor binding to the ERE as a head-to-head dimer. PMID- 2927398 TI - Somatic mutation and transcriptional deregulation of myc in endemic Burkitt's lymphoma disease: heptamer-nonamer recognition mistakes? AB - We examined the structure and expression of the myc protooncogene in DNA extracted from a primary (uncultured) endemic Burkitt's lymphoma sample designated eBL3. Dot and Northern (RNA) blot analyses demonstrated extreme levels of myc RNA in the eBL3 sample. Nearly complete sequence data of the altered myc locus isolated from eBL3 DNA demonstrated extensive mutations (duplications, insertions, and deletions) in critical myc regulatory regions. Taken together, the data support the idea that myc transcriptional deregulation in Burkitt's lymphoma disease may be a consequence of the position and number of mutations produced within and around the myc locus. Furthermore, the myc exon-1-intron-1 hypermutable PvuII site is part of a potential heptamer-nonamer recognition sequence, suggesting a mechanism for mutation in endemic Burkitt's lymphoma disease. PMID- 2927400 TI - Studies of the antigenic structure of two cross-reacting proteins, pertussis and cholera toxins, using synthetic peptides. AB - Peptide fragments of pertussis toxin subunit 1 (PT-S1) have been synthesized in order to investigate their antigenic and immunogenic activity, and to evaluate their possible use as components of a new vaccine. Two peptides (sequence 73-82, EAERAGRGTG and sequence 107-116, YVDTYGDNAG) were selected for their predictable exposure on the surface of the molecule, and a third (8-18, YRYDSRPPEDV) for its homology with the sequence 6-16 of cholera toxin subunit A (CT-A 6-16) (YRADSRPPDEI). Antipeptide polyclonal antibodies produced in rabbits, were tested in different immunoassays for their ability to interact with toxin proteins. All of them proved interactive with recombinant PT-S1 (rPT-S1); CT-A interact not only, as expected, with anti 8-18 antibodies, due to the high homology between the two toxins in this region, but also, unexpectedly, with anti 107-116 antibodies, in spite of the lack of homology of this peptide with the entire CT. We also found a direct cross-reactivity between the two toxins: anti PT and anti rPT-S1 antibodies interacted with CT-A, whereas anti CT antibodies did not recognize PT. Antipertussis antibodies also recognized the peptide 8-18, which therefore represents at least a part of an antigenic determinant of the toxin, while no interaction could be evidenced between anti-cholera antibodies and any of the peptides, thus demonstrating important differences in the antigenic structures of the two toxins. None of the antipeptide antibodies examined showed protective activity against the toxins in a Chinese hamster ovary (CHO) cell test. PMID- 2927399 TI - Peroxisome targeting signal of rat liver acyl-coenzyme A oxidase resides at the carboxy terminus. AB - To identify the topogenic signal of peroxisomal acyl-coenzyme A oxidase (AOX) of rat liver, we carried out in vitro import experiments with mutant polypeptides of the enzyme. Full-length AOX and polypeptides that were truncated at the N terminal region were efficiently imported into peroxisomes, as determined by resistance to externally added proteinase K. Polypeptides carrying internal deletions in the C-terminal region exhibited much lower import activities. Polypeptides that were truncated or mutated at the extreme C terminus were totally import negative. When the five amino acid residues at the extreme C terminus were attached to some of the import-negative polypeptides, the import activities were rescued. Moreover, the C-terminal 199 and 70 amino acid residues of AOX directed fusion proteins with two bacterial enzymes to peroxisomes. These results are interpreted to mean that the peroxisome targeting signal of AOX residues at the C terminus and the five or fewer residues at the extreme terminus have an obligatory function in targeting. The C-terminal internal region also has an important role for efficient import, possibly through a conformational effect. PMID- 2927401 TI - Reduced glutamate decarboxylase activity in the subthalamic nucleus in patients with tardive dyskinesia. AB - Glutamate decarboxylase (GAD) activity was measured in the nuclei of the basal ganglia in patients with neuroleptic-induced tardive dyskinesia (TD) and controls matched for age and premortem state. In five TD patients, who all had a sudden death, a significant decrease in GAD activity was found in the subthalamic nucleus (STN). The lowered GAD activity in the STN may represent a biochemical substrate for neuroleptic-induced TD. PMID- 2927402 TI - Off-period belching due to a reversible disturbance of oesophageal motility in Parkinson's disease and its treatment with apomorphine. AB - Two L-dopa-treated patients with Parkinson's disease who developed distressing belching during "off" periods are reported. In each case, contrast cine radiography revealed disturbed oesophageal motility which disappeared after injection of the dopamine receptor agonist apomorphine. It is suggested that central dopaminergic abnormalities may be important in the aetiology of "off period belching." PMID- 2927403 TI - The use of glutethimide for treatment of essential tremor. AB - Two patients with long-standing intention tremor that was interfering with their ability to maintain employment were treated with glutethimide. In both patients, this agent successfully suppressed tremor at doses of 1,000 mg and 4,000 mg per day. Glutethimide has been taken for as long as 14 years in one patient without evidence of side effects. PMID- 2927405 TI - Trauma as an etiologic agent in Parkinson disease. PMID- 2927406 TI - Abstracts of the Symposium on High Technology in the Quantitation of Movement Disorders. Jerusalem, Israel, June 5, 1988. PMID- 2927404 TI - Choreoathetosis induced by cyproheptadine. AB - Cyproheptadine is an antihistamine with antiserotoninergic and anticholinergic properties. It is a relatively safe drug with many varied indications for usage, which rarely produces serious adverse neurologic sequelae. Reports of involuntary movement disorder secondary to cyproheptadine are rare. We present the case of a 17-year-old overdose victim which may be the first documented instance of cyproheptadine intoxication resulting in choreoathetosis. This hyperkinesia was most likely resultant from the anticholinergic properties of cyproheptadine. Although the choreoathetoid movement resolved spontaneously, the delirious state disappeared after administration of physostigmine. PMID- 2927407 TI - Molecular characterization of thymidine kinase mutants of human cells induced by densely ionizing radiation. AB - In order to characterize the nature of mutants induced by densely ionizing radiations at an autosomal locus, we have isolated a series of 99 thymidine kinase (tk) mutants of human TK6 lymphoblastoid cells irradiated with either fast neutrons or accelerated argon ions. Individual mutant clones were examined for alterations in their restriction fragment pattern after hybridization with a human cDNA probe for tk. A restriction fragment length polymorphism (RFLP) allowed identification of the active tk allele. Among the neutron-induced mutants, 34/52 exhibited loss of the previously active allele while 6/52 exhibited intragenic rearrangements. Among the argon-induced mutants 27/46 exhibited allele loss and 10/46 showed rearrangements within the tk locus. The remaining mutants had restriction patterns indistinguishable from the TK6 parent. Each of the mutant clones was further examined for structural alterations within the c-erbA1 locus which has been localized to chromosome 17q11-q22, at some unknown distance from the human tk locus at chromosome 17q21-q22. A substantial proportion (54%) of tk mutants induced by densely ionizing radiation showed loss of the c-erb locus on the homologous chromosome, suggesting that the mutations involve large-scale genetic changes. PMID- 2927408 TI - Production of chromosome aberrations, micronuclei, and sister-chromatid exchanges by 24-keV epithermal neutrons in human G0 lymphocytes. AB - The induction of chromosome aberrations, micronuclei and sister-chromatid exchanges in human G0 lymphocytes by 24-keV epithermal neutrons has been measured. Positive linear dose responses were obtained for the 3 end points, with a tendency to saturation at higher dose for SCE production. In all cases, the responses to 24-keV neutrons were characteristic of high-LET radiations. PMID- 2927409 TI - Molecular dosimetry studies of forward mutation induced at the yg2 locus in maize by ethyl methanesulfonate. AB - The yg2 assay in Zea mays detects forward mutation in somatic cells within leaf primordia of embryos and it was used in an analysis of the molecular dosimetry of ethyl methanesulfonate (EMS). Parallel genetic and molecular dosimetry experiments were conducted in which the frequency of forward mutation and the level of covalently bound ethyl DNA adducts were determined. Prepared kernels were treated for 8 h at 20 degrees C with 1-10 mM EMS. EMS induced a direct concentration-dependent increase in mutation induction proportional to the exposure concentration (slope = 0.93). The kinetics of mutation induction demonstrated in the intact maize system were consistent with the kinetics observed earlier in in vitro model systems using cultured mammalian cells, and contrasted with the exponential increase in mutation induction characteristic of microbial species. Parallel molecular dosimetry experiments were conducted using [3H]EMS. DNA was extracted and purified from embryonic tissues containing the leaf primordia, the target tissue of the yg2 assay. A linear increase in the molecular dose was observed as a function of EMS concentration. Using concentration as a common parameter between the parallel genetic and dosimetry studies, mutation induction appeared to increase nearly in a direct proportion to the molecular dose. However, studies in other genetic systems indicate that the levels of specific DNA adducts, such as O6-ethylguanine (O6-EtGua) show a better correlation with mutation induction kinetics than molecular dose. Neither molecular dose, nor O6-EtGua levels account for differences in the absolute frequencies of mutation induction observed in different genetic systems. Therefore, reliable assessment of health risks posed to humans by chemical mutagens appears to require consideration of other factors in addition to DNA dose or adduct formation, including differences in repair capabilities and in the size of the genetic targets in humans relative to the model genetic systems under study. PMID- 2927410 TI - Statistical analysis of the micronucleus test--a modelling approach. AB - This paper suggests an approach according to the principle that 'An experimental design is related to a statistical model describing that particular design'. A simple linear model approach is presented as an alternative to earlier proposed multiple single tests which is suitable for situations in which there are just a few dose levels and expression times. Furthermore, the aim is to move from significance testing towards a modelling and estimation procedure in order to find a structure and try to evaluate what is being determined in the experiment. PMID- 2927411 TI - Time-effect relationship of chromosome aberrations in peripheral lymphocytes after radiation therapy for seminoma. AB - The time-effect relationship of dicentrics and cells containing unstable chromosome abnormalities (Cu cells) was studied in peripheral lymphocytes of 40 blood samples from 23 patients suffering from seminoma during a time period of 0 1720 days after radiation therapy. Nine patients were studied before treatment. Since the half-time for the disappearance of damaged cells from circulating blood is an increasing function of post-exposure time it can only be expressed as a differential value. The present model discriminates between the mean lifetime m for lymphocytes and a parameter q which is the differential half-time for the decline of damaged cells immediately after exposure (t = 0). If the time t is short compared with m the decline is asymptotically time-hyperbolic rather than exponential and can be described by q only. According to recalculations of previous data, comprising 30 years post exposure, m approximates 10 years. Differential half-times can be derived for any time post treatment within the analysed time period for the decline of the incidence of dicentrics. For example at the end of therapy (t = 0) the differential half-time was calculated to be 0.4 years and at 1720 days post exposure 3.6 years resulted. The corresponding values for the percentage of Cu cells cannot be derived for t = 0; at 1720 days 3.9 years resulted. PMID- 2927412 TI - The in vitro unscheduled DNA synthesis (UDS) assay in rat primary hepatocytes. Validation of improved methods for primary culture including data on the lack of effect of ionizing radiation. AB - The in vitro unscheduled DNA synthesis (UDS) assay was evaluated for inclusion in a battery of assays used at The Upjohn Company for evaluation of lead compounds in the development of new and existing drug entities. This evaluation process encompassed aspects of the isolation of hepatocytes and tests of reference mutagens and genotoxins. The flow rate of perfusion solutions and their temperatures were critical in the isolation of high viability hepatocytes in good yield. The attachment of freshly isolated hepatocytes to coverslips was greatly enhanced by coating the coverslips with type III collagen. Results of testing 12 known genotoxic agents (UV light, cyclophosphamide, 7,12-dimethylbenzanthracene, dimethylnitrosamine, diethylnitrosamine, 2-acetylaminofluorene, benzo[a]pyrene, methyl methanesulfonate, ethyl methanesulfonate, N-propyl-N'-nitro-N nitrosoguanidine, benzidine and 4-aminobiphenyl) were in agreement with the literature. The use of X-ray did not induce unscheduled DNA synthesis in hepatocytes. This latter finding draws attention to the inability of this assay to detect agents which result in 'short-patch' repair of damage. PMID- 2927413 TI - Monofunctional alkylating agent-induced S-phase-dependent DNA damage. AB - Alkylating agents are S-phase-dependent clastogenic agents: Chromosome aberrations are not observed unless the treated cells have first undergone a replicative DNA synthesis. While DNA gaps resulting from misreplication of the alkylated template are believed to underlie aberration formation, the specific alkylated DNA lesions that produce these DNA gaps are not known. To quantitate the DNA strand break induction that results from replication of an alkylated DNA template and attempt to identify those alkylated lesions which underlie DNA strand breakage. [14C]thymidine-labeled Chinese hamster ovary (CHO) cells were treated with either N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or methyl methanesulfonate (MMS) in G1 and then allowed to progress through S phase in the presence of [3H]thymidine. When analyzed at the subsequent mitosis, DNA strand breaks were found in the nonalkylated ([3H]thymidine-labeled) DNA strand. This did not appear to be the consequence of any recombinational or endonuclease mediated event and was more likely due to DNA gaps produced by incomplete replication off the alkylated template. A portion of these breaks probably result from a failure to replicate past 3-methyladenine. Differences between MNNG and MMS in the frequency of S-phase-dependent breaks they produce relative to the overall alkylation damage suggest that the O6-methylguanine lesion might also be involved in S-phase-dependent DNA strand breakage. PMID- 2927414 TI - A bootstrap analysis of four in vitro short-term test performances. AB - The present analysis is aimed at estimating the confidence intervals of a number of association measures that describe the relationships of 4 in vitro short-term tests with rodent carcinogenicity, as well as with each other. The measures considered were: sensitivity, specificity and accuracy of the short-term tests with respect to chemical carcinogens, and performance dissimilarity indices (Hamming distances). The analysis refers to Salmonella, mouse lymphoma L5178Y cell mutation, chromosomal aberrations and sister-chromatid exchanges in Chinese hamster ovary cells, and is based on the data generated in the frame of the U.S. National Toxicology Program (NTP). It exploits the properties of a statistical technique, called bootstrap, to derive from only one sample of chemicals the variability intervals of the associations that the biological systems (mutagenicity assays and rodent carcinogenicity) would show in the 'universe' of the chemical compounds. The combination of the bootstrap technique with multivariate statistical methods pointed to a remarkable robustness and reliability of the information derived from the NTP data base, and provided descriptive insights into the data. PMID- 2927415 TI - Age-specific methylation of high-mobility-group proteins of the rat liver and its modulation by spermine and sodium butyrate. AB - Liver slices from young (20 weeks) and old (117 weeks) rats were incubated with [methyl-14C]methionine in the absence or presence of spermine or sodium butyrate. The high-mobility-group (HMG) non-histone proteins were extracted from the liver with perchloric acid and separated by acid-urea polyacrylamide slab gel electrophoresis. Methylation of HMG proteins decreased drastically in old rats. Whereas spermine inhibited the methylation of total HMG proteins in young rats, it had no effect in old age. On the contrary, sodium butyrate did not change the incorporation of methyl groups into total HMG proteins of young rats, but inhibited that of old rats. Particularly, the incorporation of [14C]methyl groups into HMG 2 was enhanced but into other HMGs it was reduced by both effectors in young and old age. Such discrepancies in the methylation of HMG proteins and their differential modulation by spermine and butyrate might affect the higher order organization of chromatin and consequently destabilize the expression of genes during aging. PMID- 2927416 TI - Effect of age on endogenous DNA single-strand breakage, strand break induction and repair in the adult housefly, Musca domestica. AB - It has been suggested that genomic alterations involving DNA damage and the ability to repair such damage play an important role in cellular senescence. In this study, endogenous DNA single-strand breaks, the susceptibility of DNA to induced strand breakage and the capacity to repair these breaks were compared in postmitotic cells from young (3-day-old) and old (23-day-old) houseflies. DNA single-strand breaks did not accumulate during normal aging in the housefly. However, cells of the old flies exhibited a greater sensitivity to single-strand breakage induced by gamma-radiation and UV light. The capacity to repair these exogenously induced single-strand breaks declined with age. Results do not support the view that DNA single-strand breaks are a causal factor in aging in the housefly. An age-related increase in the susceptibility to undergo single strand breakage suggests alterations in chromatin during the aging process. PMID- 2927418 TI - About an old problem, new approaches, a new section. PMID- 2927419 TI - Molecular gerontology needs coordination. PMID- 2927417 TI - Age-dependent covalent DNA alterations (I-compounds) in rodent tissues: species, tissue and sex specificities. AB - I-compounds are non-polar covalent DNA modifications of as yet undetermined structure that tend to accumulate in an age-dependent manner in tissues of untreated animals. They are detectable by 32P-postlabeling assay because of their adduct-like properties and chromatographically resemble DNA nucleotides containing bulky/hydrophobic moieties. To determine which factors may be involved in their formation, I-compounds were examined by 32P-postlabeling in liver and kidney DNA of female and male Sprague-Dawley rats and Syrian hamsters of different ages (1, 4 and 10 months and 1, 2.5 and 9.5 months, respectively). The following results were obtained: (i) Every tissue DNA studied contained characteristic I-compounds. (ii) Patterns and amounts of I-compounds were reproducible among animals of the same kind. (iii) There were pronounced organ and species differences. (iv) I-compound patterns were sex-dependent. (v) I compound levels increased with age in all tissues studied, except in male hamster kidney, a target organ of estrogen-induced carcinogenesis. The highest levels were observed in liver and kidney of 10-month-old female rats. (vi) The rise of I compound levels was less steep during the later part of the observation period for female but not male animals. (vii) Gonadectomy decreased I-compound levels in female hamster kidney DNA, while causing a slight increase in male animals later in life. These I-compounds were identical to previously reported DNA modifications that increased in male hamster kidneys after prolonged estrogen treatment. Points, iv, vi and vii strongly implicated sex hormones in I-compound formation. The qualitative effects of species, tissue differentiation, gender and sex hormones on these DNA modifications support the hypothesis that I-compounds are formed by the binding of endogenous electrophiles to DNA. As persistent DNA alterations, they are likely to affect DNA replication and to play a role in spontaneous and chemically induced carcinogenesis and in aging. PMID- 2927420 TI - Age-dependent decline in rejoining of X-ray-induced DNA double-strand breaks in normal human lymphocytes. AB - Unstimulated human peripheral blood lymphocytes (HPBL), separated by density centrifugation from anticoagulated whole blood, were X-irradiated (30 Gy) on ice and incubated in medium at 37 degrees C for repair times of 15, 30, and 120 min. Blood donors were 18 normotensive, non-smoking Caucasians aged 23-78, free from overt pathology and not taking any medications. Neutral filter elution was used to assay DNA double-strand break (DSB) induction and completeness of DSB rejoining (plus rejoining of any X-ray-induced alkali-labile sites converted to DSBs in vitro at pH 9.6). After 30 or 120 min repair incubation, the percentage of DSBs rejoined by cells from older donors (aged 66-78 years) was less than half the percentage of DSBs rejoined by cells from younger donors (aged 23-39 and 42 57). When data from the 3 age groups were pooled, the age-related decline in percent DSBs rejoined was significant for repair times 30 min (r = -0.63, p less than 0.005) and 120 min (r = -0.64, p less than 0.005) but not for 15 min (r = 0.04). These age-related declines were observed even though DNA from older donors sustained fewer strand breaks as demonstrated by the negative correlation between donor age and DSB induction (r = -0.65, p less than 0.005). These results suggest that the efficacy of X-ray-induced DSB repair diminishes with in vivo age in unstimulated HPBL. PMID- 2927421 TI - Mutational specificities of 1'-acetoxysafrole, N-benzoyloxy-N-methyl-4 aminoazobenzene, and ethyl methanesulfonate in human cells. AB - We have used an oriP-tk shuttle vector to determine the types of mutations induced in human cells by ethyl methanesulfonate (EMS), 1'-acetoxysafrole (AcOS), and N-benzoyloxy-N-methyl-4-aminoazobenzene (BzOMAB). Plasmid DNA was treated in vitro with mutagen and electroporated into human lymphoblastoid cells. After replication of the vector in human cells, plasmids were analyzed for mutations in the herpes simplex virus type 1 thymidine kinase gene. Ethyl methanesulfonate induced predominantly GC----AT transition mutations. Treatment of the shuttle vector with AcOS induced 5 of the 6 possible base substitution mutations, including GC----AT (32%) and AT----GC (14%) transition mutations, GC----TA (9%), GC----CG (18%), and AT----TA (14%) transversion mutations, as well as a low frequency (9%) of -1 frameshift mutations at GC base pairs. Replication in human cells of DNA modified with BzOMAB yielded a significant increase (17-fold) in the frequency of deletion mutations relative to solvent-treated DNA. A majority (94%) of the point mutations induced by BzOMAB occurred at GC base pairs and were predominantly GC----AT transitions (33%) and -1 frameshift (22%) mutations, with the remainder consisting mainly of transversions at GC base pairs (28%). The broad spectrum of base substitution mutations observed for AcOS and BzOMAB may indicate the frequent insertion of a variety of bases during replicative bypass of aralkylated bases in human cells. PMID- 2927422 TI - Retroviral shuttle vectors as a tool for the study of mutational specificity (base substitution/deletion/mutational hotspot). AB - This paper summarizes the use of the retroviral shuttle vector pZipGptNeo for studies of mutational specificity in mammalian cells. This vector was constructed by the introduction of a DNA fragment containing the E. coli gpt gene into the retroviral shuttle vector pZipNeoSV(X)1. The pZipGptNeo vector was then introduced into mouse L cells to construct the A9I2 cell line. Studies utilizing the A9I2 cell line to determine the specificity of spontaneous and chemically induced mutations are summarized. The construction of a new retroviral shuttle vector and its introduction into the CHO-K1 cell line is described. Preliminary experiments suggest that spontaneous gpt gene mutations arising in CHO cells are similar to those seen in the mouse L cells. PMID- 2927423 TI - Host cell reactivation of CAT-expression vectors as a method to assay for cloned DNA-repair genes. AB - We demonstrate the feasibility of using passive host-cell reactivation of a shuttle-vector pRSVcat to detect cloned DNA-repair genes. As models, a transient expression vector, pRSVdenV, and a positive-selection vector, pRSVdenV/SVgpt, were constructed containing the T4 coliphage denV gene, coding for an ultraviolet specific endonuclease, under promotion of the Rous sarcoma virus (RSV) long terminal repeat. Cotransfection of one or three copies of pRSVdenV per UV irradiated pRSVcat molecule into xeroderma pigmentosum (XP) cells (XP12Ro[M1]) resulted in a dramatic increase in transient expression of chloramphenicol acetyl transferase (CAT) activity. XP clones stable transformed by pRSVdenV/SVgpt but not the parent cell line rescued CAT activity from this UV-irradiated reporter gene. The ability to express CAT activity from a UV-irradiated pRSVcat correlated with the presence of the structural denV gene as detected by Southern blot analysis. Post-UV irradiation colony-forming ability and DNA nucleotide excision repair synthesis were partially restored in XP clones which rescued CAT activity. These results demonstrate the feasibility of using the cloned denV gene with its well characterized pyrimidine cyclobutane dimer-specific endonuclease activity to reconstitute UV-induced DNA repair in human cells deficient in DNA repair. Measuring CAT expression from pRSVcat affords a rapid, sensitive procedure to screen for functional cloned DNA-repair genes and to test mutant cells for defects in DNA repair. PMID- 2927424 TI - Effect of DNA damage on stable transformation of mammalian cells with integrative and episomal plasmids. AB - The efficiency of stable transformation of human cells by integrative (non replicating) plasmids carrying a selectable gene has been shown to be markedly enhanced by the introduction into the plasmid DNA of bulky damage, such as cyclobutane pyrimidine dimers or psoralen photoadducts. Enhanced transformation (ET) occurs in all human cells tested, including DNA repair-deficient cells from the hereditary syndrome xeroderma pigmentosum, but significantly less, if at all, in rodent cells. ET has been observed with a variety of integrative plasmid constructs, suggesting the generality of the phenomenon; as expected, ET is due to an increase in the number of cells carrying integrated plasmid sequences. In contrast to integrative plasmids, stable transformation by episomal (autonomously replicating) plasmids derived from the Epstein-Barr virus is only depressed by the introduction of photoproducts; furthermore, pronounced inactivation of transformation mediated by episomal plasmids becomes apparent in xeroderma pigmentosum cells. Altogether, these results suggest that DNA damage increases the probability of stable insertion of heterologous non-replicating DNA into human chromosomes. Moreover, the differential sensitivity to DNA damage of human cell transformation mediated by integrative versus episomal plasmids suggests caution in using such assay to measure host cell reactivation capacity; processing of DNA damage in mammalian cells might differ significantly between intra- versus extra-chromosomal DNA. Since ET may be induced by damage outside the selectable gene carried on integrative plasmids, we propose a model that involves local disruption of chromatin structure by helix-distorting DNA lesions flanking actively transcribed sequences; alternatively, reorganization of such altered DNA structure might be favored by the presence of topoisomerase-like activities in the proximity of active genes. Because ET can also be induced by DNA damage to the recipient cells, it is speculated that similar mechanism(s) might be involved in the generation of other types of non-homologous DNA recombination in damaged human chromosomes, including oncogenic cell transformation mediated by integrative DNA viruses. PMID- 2927425 TI - Perspectives on the use of an endogenous gene target in studies of mutational specificity. AB - Mutational spectra have become increasingly important tools in generating a molecular level understanding of mutagenesis in mammalian cells. The work in this field has primarily involved the use of shuttle vector systems although some work has also been reported using endogenous cellular genes as mutational targets. In this communication we discuss the relative utility of these two approaches. We specifically focus on UV light-induced mutagenesis since this agent has been studied in both types of system. We conclude that shuttle vector and endogenous gene studies of mutagenesis are highly complementary, each possessing unique advantages. PMID- 2927426 TI - Use of shuttle vectors for the analysis of DNA damage processing in mammalian cells. PMID- 2927427 TI - Molecular mechanisms of mutagenesis in mammalian cells: present and future. PMID- 2927428 TI - An approach to the investigation of cancer in tool and die workers. I. Epidemiologic findings in a suspected cancer cluster among tool and die workers. PMID- 2927429 TI - Comment on mutagenicity of diethyl sulfate in mice and on germ-cell mutagenicity testing. PMID- 2927430 TI - The influence of alpha-tocopherol and pyritinol on oxidative DNA damage and lipid peroxidation in human lymphocytes. AB - Unscheduled DNA synthesis (UDS) and lipid peroxidation (LPO) were measured in human peripheral lymphocytes from healthy volunteers. These processes were induced by the catalytic system Fe2+-sodium ascorbate. The degree of induced LPO was measured spectrophotometrically by the thiobarbituric acid assay. UDS was detected by scintillometric measurement of the incorporation of 3H-thymidine into DNA. The protective action by fat-soluble vitamin E (D,L-alpha-tocopherol) and the artificial antioxidant pyritinol on UDS and LPO was also investigated. The system Fe2+ (2 mumole/l)-sodium ascorbate (30 mumole/l) increased the LPO level in healthy volunteers approximately 2.5 times and the incorporation of 3H thymidine by 60-70%. alpha-Tocopherol (0.2 mmole/l) very efficiently suppressed LPO processes (p less than 0.01) and the oxidative damage of DNA measured as UDS was also significantly diminished (p less than 0.05). Pyritinol had no effect on LPO and UDS under our experimental conditions. PMID- 2927431 TI - Influence of benzamide on killing and mutation of density-inhibited V79 cells by MNNG. AB - Density-inhibited V79 cells when held for 24 h in complete medium after exposure to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) show improved survival levels and decreased mutant frequencies at all dose levels, compared to cells not so held. However, when benzamide, an inhibitor of poly(ADP-ribose) synthesis was present during this 24-h holding, the improvement in survival and decrease in mutant frequencies were not observed. Rather, compared to the control, the cells became more sensitive to MNNG and mutant frequency also increased significantly for all doses studied. PMID- 2927432 TI - The induction by ionizing radiation of chromosomal aberrations in rhesus monkey pre-meiotic germ cells: effects of dose rate and radiation quality. AB - The induction of reciprocal translocations in rhesus monkey stem-cell spermatogonia was studied using multivalent analysis at metaphase of primary spermatocytes. Animals were exposed to 1 Gy gamma-rays at dose rates of 140 and 0.2 mGy/min or to 0.25 Gy acute 2 MeV neutrons. Reduction of the dose rate from 140 mGy/min to 0.2 mGy/min did not result in a lowering of the frequencies of recovered translocations of 0.43%. The neutron data indicated an RBE (neutrons vs. X-rays) of 2.1, which is clearly lower than the value of 4 obtained in the mouse. It is made plausible that in general mammalian species with high sensitivities for the cytotoxic effects of ionizing radiation, such as the rhesus monkey, will exhibit relatively high threshold dose rates below which no further reduction in aberration yield occurs, whereas in more resistant species, such as the mouse, the threshold dose rate will be at a very low level. Similarly, resistant species will show relatively high RBE values for neutron irradiation and sensitive species low ones. PMID- 2927433 TI - Formation of 8-hydroxydeoxyguanosine in DNA treated with fecapentaene-12 and -14. AB - Fecapentaene-12 and -14, direct-acting mutagens in human feces, were found to hydroxylate the C-8 position of guanine residues in DNA in vitro. Fecapentaene-12 or -14 was incubated with 0.5 mg of calf thymus DNA in 1 ml of reaction mixture at pH 7.4 for 2 h at 37 degrees C in the dark, and then 8-hydroxydeoxyguanosine (8-OH-dG) was analyzed. In these conditions 8-OH-dG was formed dose-dependently at levels of 1.1-4.6 residues/10(4) dG with concentrations of 0.5-3.0 mM of fecapentaene-12. Similar results were obtained with fecapentaene-14. The amount of 8-OH-dG in untreated DNA was 0.2-0.3 residue/10(4) dG. PMID- 2927434 TI - Increased frequency of oxidant-mediated DNA strand breaks in mononuclear leucocytes exposed to activated neutrophils from cigarette smokers. AB - Following activation with the synthetic chemotactic tripeptide FMLP, potentiated by cytochalasin B (CB), blood neutrophils from cigarette smokers generated greater amounts of both extracellular and intracellular reactive oxidants than cells from non-smoking control subjects. FMLP/CB-activated neutrophils from cigarette smokers also inflicted increased oxidant-mediated damage to the DNA of cocultured mononuclear leucocytes, which was prevented by the inclusion of superoxide dismutase and catalase individually and in combination. These observations demonstrate that cigarette smoking primes phagocytes to generate increased amounts of potentially carcinogenic reactive oxidants. PMID- 2927435 TI - The rat-liver carcinogen N-nitrosomorpholine initiates unscheduled DNA synthesis and induces micronuclei in the rat liver in vivo. AB - Alkylation of DNA is generally accepted as the primary event in the carcinogenicity of nitrosamines. However, the cyclic nitrosamine N nitrosomorpholine (NMOR), a potent rat hepatocarcinogen, has been reported as binding at very low levels to the liver DNA of treated rats. This led us to investigate the activity of NMOR in two in vivo rat-liver genotoxicity assays- for the induction of unscheduled DNA synthesis (UDS) and the production of micronucleated hepatocytes in the liver micronucleus assay (LMN). Rats treated with oral doses of NMOR (10-200 mg/kg) gave a positive liver UDS response either 2.5 h or 12 h after dosing. Similarly, treatment with oral doses of NMOR (10 or 100 mg/kg) followed by mitogenic stimulation with 4-acetylaminofluorene (4AAF) resulted in high incidences of micronucleated hepatocytes in the LMN assay. These data confirm that the genotoxicity reported for NMOR in vitro can be reproduced in vivo and that NMOR interacts with liver DNA of treated rats. Earlier reports of only very weak binding of radiolabelled NMOR to rat liver DNA in vivo are discussed within the context of these data. PMID- 2927436 TI - A genetic method to quantitate induced chromosome breaks using a mouse/human monochromosomal hybrid cell line: identification of potential clastogenic agents. AB - A genetic assay to detect the clastogenic potential of environmental agents is described. This assay is based on the cloning efficiency of cells in a medium that permits the growth of cells following loss of a specific chromosome segment resulting from a chromosome break. For this purpose a mouse/human hybrid cell line R12-2 containing a dominantly marked chromosome 5 as the only human component has been constructed. This chromosome 5 carries two dominant selectable markers, Ecogpt and the gene for sensitivity to diphtheria toxin (DTs). Ecogpt codes for the enzyme xanthine-guanine phosphoribosyltransferase which allows selection for cells containing chromosome 5 or the segment carrying Ecogpt as judged by growth in medium supplemented with mycophenolic acid and xanthine (MX medium). Human cells are sensitive to 10(-13) M DT, whereas mouse cells are resistant to 10(-7) M DT and DTs is expressed as a dominant phenotype. Cultivation of R12-2 cells in the medium containing 10(-13) M DT permit the selection of cells that have lost chromosome 5 or the segment carrying DTs. The presence of two selectable markers on the same chromosome permits the identification and quantitation of cells for the selective loss of a specific chromosome segment. Growth of R12-2 cells in MX medium containing 10(-13) M DT therefore, provides a convenient method to determine the frequency of clastogen induced breaks in chromosome 5. The utility of the proposed genetic assay is assessed using X-irradiation as a model clastogen. Our results clearly show a dose related response that is consistent with cytogenetic observations. PMID- 2927437 TI - Acentric chromosomal fragments and micronuclei: the time-displacement factor. PMID- 2927438 TI - Complete culture medium is better than low folate medium for detecting increased chromosome aberrations in smokers in 48-h lymphocyte cultures. AB - We compared chromosome breakage in parallel, 48-h lymphocyte cultures established from smokers and nonsmokers using minimal essential medium (MEM) and MEM without folate (MEM-FA). There was a statistically significant, higher frequency of aberrations for smokers than for nonsmokers in cells cultured in MEM, but not in those cultured in MEM-FA. Thus, these data support the recommendation of the World Health Organization (1985) that population monitoring studies for exposure assessment should not use a low folate medium. PMID- 2927439 TI - Mutagenicity of nitrofurantoin and furazolidone in Chinese hamster ovary cell strains. PMID- 2927440 TI - The HLA-A mutation assay: improved technique and normal results. AB - The HLA-A assay for detection of mutant lymphocytes has been modified, principally by incorporation of an overnight-incubation step which has resulted in improved immunoselection. For 83 estimations on cells from 21 normal individuals with a mean age of 35, the in vivo mutant frequency was 2.99 X 10(-5) +/- 1.48 X 10(-5) (mean +/- 1 SD). For 11 estimations on cells from 10 elderly individuals with a mean age of 78, the mutant frequency was significantly greater, being 7.16 X 10(-5) +/- 4.06 X 10(-5). Similar results were obtained when HLA-A2 or HLA-A3 mutants were enumerated. Mutant frequency measured at the HLA-A locus is almost an order of magnitude greater than that measured at the hypoxanthine phosphoribosyl transferase locus, but at least the major part of this difference is likely to be due to factors other than a difference in genetic stability between the two loci. PMID- 2927441 TI - Localization and pattern of expression of a female specific mRNA in Schistosoma mansoni. AB - To understand mechanisms involved in sex-specific gene expression in Schistosoma mansoni, a cDNA (fs800) was isolated that hybridized to an 800 nucleotide mRNA present in high levels only in mature female worms. The fs800 cDNA sequence was characterized by two long open reading frames and central stretches of repeated amino acids. Fs800 did not share similarities with other known sequences in computer searches. In situ hybridization, however, revealed that the mRNA corresponding to fs800 was found only in female vitelline cells, suggesting that the product of this gene may be involved in the production or function of eggs. Fs800 is developmentally regulated as expression of this gene is dependent on the maturity of female worms. Furthermore, during in vitro culture, when female worms are known to stop egg production, expression of fs800 selectively ceased. PMID- 2927443 TI - Characterization of tubulin from Brugia malayi and Brugia pahangi. AB - The tubulins of Brugia malayi and B. pahangi were similar with respect to concentration (mg tubulin per mg soluble protein), electrophoretic and isoelectric mobility, reaction in Western blots with anti-tubulin monoclonal antibodies, and isoform patterns. Tubulin was estimated to account for 2.8% and 2.9% of soluble protein in B. malayi and B. pahangi extracts, respectively. Tubulins from Brugia nematodes have been partially purified by polylysine agarose chromatography and with taxol. Western blots with alpha- and beta-tubulin monoclonal antibodies confirmed the presence of tubulin. The mobility of Brugia tubulins on sodium dodecyl sulfate polyacrylamide gel electrophoresis was very similar to that of N. brasiliensis and rat brain tubulins. The isoelectric range for Brugia alpha- and beta-tubulin isoforms was pH 5.4-4.7. Western blots with anti-tubulin monoclonal antibodies revealed 4-5 isoforms of alpha-tubulin and 4-5 isoforms of beta-tubulin for Brugia nematodes. PMID- 2927442 TI - Giardia cyst wall-specific carbohydrate: evidence for the presence of galactosamine. AB - Gas chromatographic (GC), mass spectrometric (MS), lectin binding and enzymatic analyses of the carbohydrates from Giardia cyst walls, intact cysts and trophozoites were performed to investigate the carbohydrate composition of Giardia cyst walls and to test the hypothesis that the Giardia cyst wall is composed largely of chitin. Galactosamine, verified by MS, was present in Giardia cyst walls and intact cysts (ca. 47 nmol 10(-6) cysts). Since not even trace amounts of it were detected in trophozoites by either GC or lectin binding, galactosamine is hypothesized to be a cyst wall-specific amino hexose. Based on the putative binding affinity of Phaseolus limensis lectin, galactosamine may be present in cyst walls as N-acetylgalactosamine. Neither glucosamine nor sialic acid were detected in as much as 11 mg dry weight of cysts, cyst walls, or trophozoites. Glucose, the most abundant carbohydrate, and ribose were detected in Giardia cysts and trophozoites. Galactose (ca. 10 nmol 10(-6) cysts) was detected in cysts but not in trophozoites. The lack of detectable levels of (1) glucosamine in cyst wall hydrolysates, (2) cyst staining by Calcofluor M2R, (3) endogenous chitinase activity and (4) N-acetylglucosamine when cysts served as a substrate for exogenous chitinase suggests that the Giardia cyst wall is not composed largely of chitin as previously reported. beta-N Acetylgalactosaminidase, EC 3.2.1.32, activity was detected in cysts and trophozoites and represents the first carbohydrate splitting hydrolase detected in Giardia. PMID- 2927444 TI - cDNA encoding an immunogenic region of a 22 kilodalton surface protein of Eimeria acervulina sporozoites. AB - cDNA encoding an immunogenic region of a 22 kDa surface protein of Eimeria acervulina sporozoites was cloned and expressed in the bacteriophage lambda gt11 vector. The recombinant beta-galactosidase fusion protein, designated MA1, has an apparent molecular size of 125 kDa. Immunofluorescence staining of intact E. acervulina sporozoites and merozoites and immunoblotting of 125I-surface labeled protein from both stages revealed exclusive expression of the cloned cDNA in the sporozoite stage. The gene encoding the 22 kDa surface protein appears to exist as a single copy sequence as revealed by Southern blot hybridization utilizing the cDNA insert as a probe. Although not recognized by immune serum, purified recombinant MA1 antigen induced significant in vitro activation of T lymphocytes obtained from chickens immune to E. acervulina. DNA sequencing and hydropathic analysis of the predicted amino acid sequence revealed a central hydrophilic region surrounded by two hydrophobic areas which may represent exposed and transmembrane regions of the protein. PMID- 2927445 TI - Transcripts from the co-transposed segment of variant surface glycoprotein genes are in Trypanosoma brucei polyribosomes. AB - In Trypanosoma brucei the 5' proximal flanking sequences of a variant surface glycoprotein (VSG) gene, the co-transposed segment, are transcribed in a variant antigenic type- and stage-specific fashion along with the VSG gene. The precursor transcripts are subsequently processed to yield smaller transcripts from the co transposed segment as well as the VSG mRNA. These co-transposed segment transcripts are quite abundant, polyadenylated and contain the spliced leader sequence, all characteristics of trypanosome mRNAs. We have found that all of the co-transposed segment transcripts from two VSG genes are present in polyribosomes. The nucleotide sequence of much of the co-transposed segment of one of these VSG genes, however, has no open reading frames coding for proteins longer than 49 amino acids. These results suggest that co-transposed segment transcripts do not encode essential proteins even though they are present in polyribosomes and may be translated. PMID- 2927446 TI - Filarial surface antigens: the major 29 kilodalton glycoprotein and a novel 17 200 kilodalton complex from adult Brugia malayi parasites. AB - Adult Brugia malayi nematode parasites possess a range of cuticular and epicuticular molecules which may be defined by various surface-labelling techniques. We present here evidence that at least two distinct antigens are associated with the surface, a glycoprotein of 29 kDa, and a complex of twelve components forming a regular series or 'ladder' between 17 and 200 kDa (17/200 kDa) which have not previously been described. Each of these products is antigenic in infected hosts, although responses in infected humans to the 17/200 kDa are relatively weak. Digestion of the 29 kDa antigen with proteases and endoglycosidases indicates that it is closely conserved between B. malayi and B. pahangi, and that it carries at least two N-linked oligosaccharide chains each of 1.5-2 kDa. By contrast, a smaller surface-labelled antigen of 15 kDa shows no glycosylation by either lectin adherence or endoglycosidase digestion assays. Trypsin treatment of intact, labelled parasites results in cleavage of 29 kDa molecules isolated 17/200 kDa 'ladder' to trypsin abolishes all bands except the 17 kDa base unit. Both the 29 kDa and 17/200 kDa antigens can be recovered as water-soluble molecules by homogenisation of the parasite in the absence of detergent, or by disruption of the cuticle with reducing agents such as 2 mercaptoethanol. In the presence of such agents, both the 17/200 kDa series and the 29 kDa glycoprotein are shed rapidly from intact parasites. Finally, two dimensional electrophoretic analysis shows that while the 29 kDa glycoprotein is strongly basic and the 15 kDa acidic, the 17/200 kDa antigens form a related series of neutral pI. PMID- 2927447 TI - Identification, synthesis and immunogenicity of cuticular collagens from the filarial nematodes Brugia malayi and Brugia pahangi. AB - The major structural proteins of the cuticle of the filarial nematode parasites Brugia malayi and Brugia pahangi were identified by extrinsic iodination and sensitivity to clostridial collagenase. At least 16 acidic components were identified in adult worms by 2-dimensional electrophoresis, with molecular weights ranging from 35,000 to 160,000. These proteins appear to be cross-linked by disulphide bonds, and localised in the basal and inner cortical layers of the cuticle. The outer cortex, containing the epicuticle, is insoluble in 1% sodium dodecyl sulphate and 5% 2-mercaptoethanol, and can be isolated free of cellular material. Despite their inaccessibility to the immune system in intact worms, antibodies to the cuticular collagens are provoked in humans infected with a variety of filarial parasites. Immunological cross-reactivity was demonstrated between a 35 kDa component and human type IV (basement membrane) collagen. Autoantibodies to type IV collagen were detected in a number of individuals with lymphatic filariasis, although no correlation could be drawn with observed pathology. Synthesis of cuticular collagens is discontinuous, occurs at negligible levels in mature adult male worms, and does not appear to involve the production of small molecular weight precursors, in contrast to Caenorhabditis elegans. Hybridisation with a heterologous cDNA probe coding for the alpha 2 chain of chicken type 1 collagen suggests that they are encoded by a multigene family. PMID- 2927448 TI - Genes encoding the major surface glycoprotein in Leishmania are tandemly linked at a single chromosomal locus and are constitutively transcribed. AB - The major surface glycoprotein of Leishmania, gp63, is encoded by a small multi gene family of tandemly linked genes which map to a single chromosome. For Leishmania major, there are five 3.1 kilobasepair (kb) direct repeat units which include a 1.8-kb open reading frame and a 1.3-kb intergenic or spacer region. In addition, there is a single gene copy linked as a direct repeat but separated from the tandem array of gp63 genes by about 8 kb. The restriction enzyme map of the repeat unit is highly conserved among the gene copies. The regions which flank the tandemly repeated genes diverge outside of the 3.1-kb repeat unit. Transcription of the gp63 gene locus is constitutive as the 3-kb transcript was present in promastigotes as well as in amastigotes. A minor 6-kb gp63 gene transcript was also detected in Northern blot analysis which could signify the transcription of the genes as a polycistronic or multigene precursor RNA. PMID- 2927449 TI - Eight-year results of a randomized clinical trial comparing total mastectomy and lumpectomy with or without irradiation in the treatment of breast cancer. AB - In 1985 we presented results of a randomized trial involving 1843 women followed for five years that indicated that segmental breast resection (lumpectomy) followed by breast irradiation is appropriate therapy for patients with Stage I or II breast cancer (tumor size, less than or equal to 4 cm), provided that the margins of the resected specimens are free of tumor. Women with positive axillary nodes received adjuvant chemotherapy. Lumpectomy followed by irradiation resulted in a five-year survival rate of 85 percent, as compared with 76 percent for total mastectomy, a rate of survival free of distant disease of 76 percent, as compared with 72 percent, and a disease-free survival rate of 72 percent, as compared with 66 percent. In the current study, we have extended our observations through eight years of follow-up. Ninety percent of the women treated with breast irradiation after lumpectomy remained free of ipsilateral breast tumor, as compared with 61 percent of those not treated with irradiation after lumpectomy (P less than 0.001). Among patients with positive axillary nodes, only 6 percent of those treated with radiation and adjuvant chemotherapy had a recurrence of tumor in the ipsilateral breast. Lumpectomy with or without irradiation of the breast resulted in rates of disease-free survival (58 +/- 2.6 percent), distant-disease-free survival (65 +/- 2.6 percent), and overall survival (71 +/- 2.6 percent) that were not significantly different from those observed after total mastectomy (54 +/- 2.4 percent, 62 +/- 2.3 percent, and 71 +/- 2.4 percent, respectively). There was no significant difference in the rates of distant-disease-free survival (P = 0.2) or survival (P = 0.3) among the women who underwent lumpectomy (with or without irradiation), despite the greater incidence of recurrence of tumor in the ipsilateral breast in those who received no radiation. We conclude that our observations through eight years are consistent with the findings at five years and that these new findings continue to support the use of lumpectomy in patients with Stage I or II breast cancer. We also conclude that irradiation reduces the probability of local recurrence of tumor in patients treated with lumpectomy. PMID- 2927450 TI - Recurrence of thyroid nodules after surgical removal in patients irradiated in childhood for benign conditions. AB - To determine the incidence of benign thyroid nodules and the risk factors for their recurrence after surgical removal, we followed 511 patients for 1 to 40.6 years (median, 11.2) after surgery for benign thyroid nodules arising after local irradiation for unrelated benign diseases in childhood. Recurrent thyroid nodules developed in 100 patients (19.5 percent). The risk of recurrence correlated inversely with the amount of thyroid tissue removed. Women had a higher recurrence rate than men (28.4 percent vs. 10.3 percent; P less than 0.05). Among the 299 patients who had been treated with thyroid hormone at the discretion of their physicians to suppress thyroid-stimulating hormone, 25 had recurrences (8.4 percent), as compared with 72 of 201 patients who did not receive thyroid hormone (35.8 percent) (hazard ratio taking into account the extent of surgery and the patient's sex, 2.5; 95 percent confidence interval, 1.5 to 4.1). Histologic analysis of the 73 tissue samples from patients with recurrences showed that 14 samples (19.2 percent) were malignant. Thyroid hormone treatment had no effect on the rate of thyroid cancer. We conclude that radiation-associated benign thyroid nodules have a high recurrence rate, similar to that reported among nonirradiated patients with benign thyroid nodules. We also conclude that treatment with thyroid hormone decreases the risk of benign recurrences, particularly in women, but not the risk of cancer. PMID- 2927451 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 13-1989. A 76-year-old woman with multiple bone lesions and thrombocytopenia. PMID- 2927452 TI - More on heparin for prevention of atherosclerosis. PMID- 2927453 TI - Severity of sleep apnea and automobile crashes. PMID- 2927454 TI - Arsenic intoxication in a cocaine abuser. PMID- 2927455 TI - Neurobiology of depression. PMID- 2927456 TI - Using restraints in the elderly because of fear of litigation. PMID- 2927457 TI - Cephawhatchamacallums. PMID- 2927458 TI - Pharmaceutical advertising to left-handed physicians. PMID- 2927459 TI - Proposals for reform of the British National Health Service. PMID- 2927460 TI - The effect of nicotine on energy expenditure during light physical activity. AB - The metabolic effects of nicotine have been implicated in the relation between smoking and lower body weight. This study examined whether the nicotine-induced increase in the metabolic rate observed at rest is also present during physical activity. We compared the energy expenditure of 10 male smokers receiving nicotine (15 micrograms per kilogram of body weight) with that of 10 male smokers receiving placebo on two occasions, each including a period of rest and a period of exercise on a modified bicycle ergometer at workloads designed to simulate and standardize light daily activity. All had abstained from cigarette smoking the night before the study. The excess energy expenditure attributable to nicotine was more than twice as great during exercise (difference between groups, 0.51 kJ per kilogram per hour, or 12.1 percent of the metabolic rate at rest; P less than 0.001) than during rest (0.23 kJ per kilogram per hour, or 5.3 percent of the metabolic rate at rest; P less than 0.05). In contrast, the expenditure was not affected by placebo during exercise or rest in the smokers or in a comparison group of 10 non-smokers, indicating that smoking status has no long-term metabolic effect in the absence of short-term nicotine intake. We conclude that the relatively small metabolic effect of nicotine when the subject is at rest is enhanced during light exercise. Our data also suggest that the weight gain that often follows smoking cessation may be influenced not only by nicotine intake but also by the level of physical activity a smoker typically engages in while smoking. PMID- 2927462 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 14-1989. An 82-year-old woman with a complete left facial palsy and a left mastoid mass. PMID- 2927461 TI - Mapping and sequencing the human genome. PMID- 2927463 TI - Cigarette smoking and body weight. PMID- 2927464 TI - Economic incentives in clinical investigation. PMID- 2927465 TI - Cancer-causing substances in food, drugs, and cosmetics. PMID- 2927466 TI - The relation between AIDS cases and HIV prevalence. PMID- 2927467 TI - Risk of stroke from carotid bruits. PMID- 2927468 TI - Outpatient versus inpatient cardiac catheterization. PMID- 2927469 TI - Antibiotics for the treatment of febrile children with neutropenia and cancer. PMID- 2927471 TI - The need for quality assurance in mammography. PMID- 2927472 TI - Prenatal care and low birth weight among blacks and whites. PMID- 2927470 TI - Autosomal dominant spondyloarthropathy. PMID- 2927473 TI - Increasing severity of asthma from 1960 to 1987. PMID- 2927474 TI - Care of the VIP patient. PMID- 2927475 TI - Heimlich maneuver for esophageal obstruction. PMID- 2927476 TI - Incomprehensible hospital bills: educating the source. PMID- 2927477 TI - Controlling AIDS in Cuba. The logic of quarantine. PMID- 2927478 TI - HIV-1, HIV-2, and HTLV-I infection in high-risk groups in Brazil. AB - We conducted a serologic survey for antibodies to human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) and human T-cell lymphotropic virus Type I (HTLV I) in 704 Brazilians with the acquired immunodeficiency syndrome (AIDS) or at risk for it. The study population included 70 homosexual men (11 of whom were prostitutes), 58 bisexual men (19 of whom were prostitutes), 101 female prostitutes from three socioeconomic groups, 13 wives of men with hemophilia who were seropositive for HIV-1 antibodies, and 47 blood donors with positive Venereal Disease Research Laboratory tests for syphilis, all from Rio de Janeiro; 86 female prostitutes from two rural towns in Minas Gerais; 133 patients with AIDS from Sao Paulo; and 196 men with bleeding disorders who were seropositive for HIV-1 antibodies on enzyme-linked immunosorbent assay, from Sao Paulo and Rio de Janeiro. The prevalence of HIV-1 infection was highest in the homosexual male prostitutes (45 percent), the wives of patients with hemophilia (38 percent), the bisexual men (28 percent), the homosexual men who were not prostitutes (19 percent), and the female prostitutes from the lower class (9 percent). Combined HIV-1 and HIV-2 infection was found in 3 percent of the patients with AIDS and in 1 percent of the homosexual men. The prevalence of HTLV-I infection ranged from 1 percent in rural female prostitutes to 13 percent in HIV-1-positive men with bleeding disorders in Rio de Janeiro. Combined HIV-1 and HTLV-I infection occurred in 1 to 11 percent of some male subgroups. We conclude that in Brazil HIV-1 infection is already well established among homosexuals, bisexuals, and lower-class female prostitutes, with bisexual men probably acting as a bridge between the heterosexual and homosexual communities, that HTLV-I infection is prevalent in groups at risk for AIDS, and that HIV-2 infection has already been introduced into the country. PMID- 2927479 TI - A randomized trial of nonoperative treatment for perforated peptic ulcer. AB - To determine whether surgery could be avoided in some patients with perforated peptic ulcer, we conducted a prospective randomized trial comparing the outcome of nonoperative treatment with that of emergency surgery in patients with a clinical diagnosis of perforated peptic ulcer. Of the 83 patients entered in the study over a 13-month period, 40 were randomly assigned to conservative treatment, which consisted of resuscitation with intravenous fluids, institution of nasogastric suction, and intravenous administration of antibiotics (cefuroxime, ampicillin, and metronidazole) and ranitidine. Eleven of these patients (28 percent) had no clinical improvement after 12 hours and required an operation. Two of the 11 had a perforated gastric carcinoma, and 1 had a perforated sigmoid carcinoma. The other 43 patients were assigned to immediate laparotomy and repair of the perforation. One of these patients was found to have a perforated gastric carcinoma. The overall mortality rates in the two groups were similar (two deaths in each, 5 percent), and did not differ significantly in the morbidity (infection, cardiac failure, or renal failure) rates (40 percent in the surgical group and 50 percent in the nonsurgical group). The hospital stay was 35 percent longer in the group treated conservatively. Patients over 70 years old were less likely to respond to conservative treatment than younger patients (P less than 0.05). We conclude that in patients with perforated peptic ulcer, an initial period of nonoperative treatment with careful observation may be safely allowed except in patients over 70 years old, and that the use of such an observation period can obviate the need for emergency surgery in more than 70 percent of patients. PMID- 2927480 TI - Mechanisms of response to treatment in autoimmune thrombocytopenic purpura. AB - To determine the mechanisms of an increase in the platelet count after therapy for autoimmune thrombocytopenic purpura, we determined the survival time and localization of radiolabeled autologous platelets and measured platelet associated immunoglobulin levels before and after prednisone therapy or splenectomy in 19 patients with the disease. Eleven of 12 patients (92 percent) responded to prednisone with a mean threefold increase in the platelet count, resulting from increased platelet production (P less than 0.005); platelet survival was unchanged. Treatment with steroids failed in only one patient, whose pretreatment platelet production was already above normal. After splenectomy, 6 of 10 patients had a mean fourfold rise in the platelet count that correlated with increased platelet survival (P less than 0.005), together with improved platelet recovery (the percentage of platelets circulating in the blood immediately after the injection). Platelet production was unchanged. Base-line 111In-labeled platelet localization in the liver was normal in five patients in whom splenectomy was effective and increased to above normal in two of three in whom it was ineffective. Total platelet localization in the liver and spleen decreased by more than half after successful splenectomy (P less than 0.001), whereas it decreased by less than 25 percent after unsuccessful splenectomy. Platelet-associated immunoglobulin levels neither predicted nor correlated with treatment responses to prednisone or splenectomy. We conclude that prednisone improves platelet counts primarily by increasing platelet production, whereas the effect of splenectomy is to prolong platelet survival. Baseline measurements of platelet turnover and of platelet localization in the liver may be helpful in predicting the response to prednisone or splenectomy, respectively. PMID- 2927481 TI - Impaired neurogenic and endothelium-mediated relaxation of penile smooth muscle from diabetic men with impotence. AB - Relaxation of the smooth muscle of the corpora cavernosa of the penis is necessary for penile erection. To determine the relation of impaired relaxation to impotence in diabetic patients, we performed an in vitro examination of corpus cavernosum tissue obtained at the time of implantation of a penile prosthesis in 21 diabetic and 42 nondiabetic men with impotence. Contraction was induced in isolated strips of corporal smooth muscle by norepinephrine; then relaxation was assessed with electrical stimulation of autonomic nerves and with the administration of three agents: acetylcholine, which is known to be mediated by endothelium-derived relaxing factor; papaverine; and sodium nitroprusside. The latter two act directly on smooth muscle (i.e., they are endothelium independent). Autonomically mediated relaxation with electrical stimulation was less pronounced in the smooth muscle from diabetic men (n = 18) than in the smooth muscle from nondiabetic men (n = 24; P = 0.001). The degree of impairment increased with the duration of diabetes (r = 0.61, P = 0.007). Endothelium dependent relaxation was also impaired, as evidenced by a lower degree of muscle relaxation after the administration of acetylcholine in the tissue from diabetic men (n = 16) than in that from nondiabetic men (n = 22; P = 0.001). The adverse effects of diabetes persisted after we controlled for smoking and hypertension. Endothelium-independent relaxation after the administration of nitroprusside and papaverine was similar in tissue from the diabetic and nondiabetic men. We conclude that diabetic men with impotence have impairment in both the autonomic and the endothelium-dependent mechanisms that mediate the relaxation of the smooth muscle of the corpora cavernosa. These findings may provide a rationale for the treatment of diabetic men with impotence by intracavernosal injection of vasodilators to induce endothelium-independent relaxation of the smooth muscle. PMID- 2927482 TI - Identification of high-risk and low-risk subgroups of patients with mitral-valve prolapse. AB - Mitral-valve prolapse is a common cardiac valvular disorder with a wide range of severity and diverse clinical outcomes. The lack of a standard definition of mitral-valve prolapse may explain the variation in reported complication rates. To identify high-risk and low-risk subgroups, we retrospectively analyzed clinical and two-dimensional echocardiographic data from 456 patients with mitral valve prolapse. Mitral-valve prolapse was defined on the basis of echocardiographic findings as systolic displacement into the left atrium of one or both leaflets beyond the plane of the mitral annulus in the parasternal long axis view. Two groups of patients were compared: those with thickening of the mitral-valve leaflets and redundancy (designated the classic form; n = 319) and those without leaflet thickening (designated the nonclassic form; n = 137). The two groups were similar in age and sex ratio. Complications or a history of complications was more prevalent in the classic than the nonclassic form: infective endocarditis, 3.5 percent and 0 percent, respectively (P less than 0.02); moderate-to-severe mitral regurgitation, 12 percent and 0 percent (P less than 0.001); and the need for mitral-valve replacement, 6.6 percent and 0.7 percent (P less than 0.02). However, the frequency of stroke was similar in the two groups: 7.5 percent and 5.8 percent (P not significant). We conclude that in a selected population of patients with mitral-valve prolapse, those with the classic form (leaflet thickening and redundancy) are at higher risk than those without these features for the infectious and hemodynamic complications of mitral valve prolapse, but not for stroke. PMID- 2927483 TI - Treatment and prophylaxis of Isospora belli infection in patients with the acquired immunodeficiency syndrome. AB - Enteric infection with the protozoan Isospora belli is common in patients with the acquired immunodeficiency syndrome (AIDS) and causes severe diarrhea. I. belli responds well to treatment with trimethoprim-sulfamethoxazole, but there is a high rate of recurrence. To investigate the effect of long-term prophylaxis, we studied 32 Haitian patients with AIDS complicated by I. belli infection and chronic diarrhea. All were treated with trimethoprim (160 mg) and sulfamethoxazole (800 mg), given orally four times a day for 10 days; the patients were then randomly assigned to receive 500 mg of sulfadoxine and 25 mg of pyrimethamine weekly, 160 mg of trimethoprim and 800 mg of sulfamethoxazole three times a week, or placebo. Half of the patients (5 of 10) who received placebo had recurrent, symptomatic isosporiasis a mean of 1.6 months after the initial treatment. All 22 patients who received either trimethoprim sulfamethoxazole or sulfadoxine-pyrimethamine remained asymptomatic. I. belli was identified in the stools of only one of these patients, who was receiving trimethoprim-sulfamethoxazole. The study medications were generally well tolerated but had to be discontinued in the cases of two patients because of severe pruritus. In 10 patients, the prophylactic regimen has been continued for a mean of 16 months without recurrent isosporiasis. We conclude that isosporiasis in patients with AIDS can be treated effectively with a 10-day course of trimethoprim-sulfamethoxazole and that recurrent disease can subsequently be prevented by ongoing prophylaxis with either trimethoprim-sulfamethoxazole or sulfadoxine-pyrimethamine. PMID- 2927484 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 16-1989. A 36-year-old man with peripheral vascular disease. PMID- 2927485 TI - Diagnosis and prognosis of mitral-valve prolapse. PMID- 2927486 TI - The politics of transplantation of human fetal tissue. PMID- 2927487 TI - Morality for the medical-industrial complex. PMID- 2927488 TI - An initiative to evaluate and improve medical practice. PMID- 2927490 TI - Screening for celiac disease. PMID- 2927489 TI - Will we face a crisis in biomedical-research brainpower in the 21st century? PMID- 2927492 TI - Better health ahead. PMID- 2927493 TI - Hair-raising scheme. PMID- 2927491 TI - Gunshot wounds to legs in drug runners. PMID- 2927494 TI - Shake-up in store for Britain's biologists. PMID- 2927495 TI - Animal patents. Transgenic sticky issues. PMID- 2927496 TI - New carp park ahead. PMID- 2927498 TI - Chernobyl. Soviet data made public. PMID- 2927497 TI - Abortion. French drug under attack. PMID- 2927499 TI - Distinguishing fraud from error. PMID- 2927500 TI - Rise and fall of Western diseases. PMID- 2927501 TI - Antigen receptor tail clue. PMID- 2927502 TI - Mate guarding as paternity insurance in Idaho ground squirrels. AB - Following a copulation, males in many species of vertebrates (particularly birds) and invertebrates remain near the inseminated female and repel other suitors with displays or force. Guarding males must delay resumption of competitive mate searching, but they may insure their paternity by reducing possibilities for secondary matings and sperm competition. Among mammals, post-copulatory mate guarding has been reported in rodents, mongooses, ungulates and primates, including humans, but the effects of such behaviour on male reproductive success have not been determined genetically. I report here that mate guarding by male Idaho ground squirrels (Spermophilus brunneus) enhances a male's probability of paternity. Furthermore, an analysis based on game theory shows that mate guarding is an evolutionarily stable strategy for male S. brunneus, but not male Belding's ground squirrels (S. beldingi), which resume searching once copulation is completed. PMID- 2927503 TI - Separate lineages of T cells expressing the alpha beta and gamma delta receptors. AB - The T-cell antigen receptor is a heterodimer molecule composed of either alpha beta or gamma delta chains. The alpha beta receptor molecules are expressed mainly in CD4+ CD8- and CD4- CD8+ T cells (helper and killer T cells respectively), whereas the gamma delta receptor molecules are expressed mainly in CD4- CD8- T cells. CD4+CD8- and CD4-CD8+ T cells arise from a class of CD4-CD8- T cells during thymus development, raising the question of whether cells rearranging their gamma delta receptors later give rise to alpha beta T cells by further rearrangements of their receptor genes, or whether rearrangements and expression of the receptor genes occur in separate lineages. The delta-chain gene is located between the V alpha (variable) and J alpha (joining) gene segments, and when the rearrangements allowing alpha- and beta-receptors occur, the DNA between these segments is deleted as small circles which can be isolated from developing thymocytes. The rearrangement status of the delta-chain gene in the alpha-circles can therefore be investigated to see whether alpha-chain and delta chain expression occur in parallel lineages or sequentially within a lineage. We find that the delta-chain gene in the T-cell receptor alpha-circles has a germline configuration, indicating that alpha beta and gamma delta T cells are distinct lineages. PMID- 2927505 TI - Activists infiltrate Stanford. PMID- 2927504 TI - Human embryo experiment banned. PMID- 2927506 TI - Cancer data are puzzling. PMID- 2927507 TI - Gel electrophoresis. DNA molecules observed. PMID- 2927508 TI - Regulation of kinase activity. PMID- 2927509 TI - The Drosophila gene torso encodes a putative receptor tyrosine kinase. AB - The maternal gene torso, required for determination of anterior and posterior terminal structures in the Drosophila embryo, was cloned using P-element tagging. Genetic evidence suggests that the action of the gene product is spatially restricted to the terminal regions; the torso messenger RNA, however, is evenly distributed. Structural similarities of the predicted torso protein with growth factor receptor tyrosine kinases suggest that the spatial restriction of torso activity results from a localized activation of the torso protein at the anterior and posterior egg pole. PMID- 2927510 TI - Functional significance of the Kunitz-type inhibitory domains of lipoprotein associated coagulation inhibitor. AB - Blood coagulation can be initiated when factor VII or VIIa, a plasma protease, binds to its essential cofactor, tissue factor (TF), and proteolytically activates factors IX and X, triggering a cascade of events which eventually leads to the formation of thrombin and a fibrin clot. Plasma contains a lipoprotein associated coagulation inhibitor (LACI) which inhibits activated factor X (Xa) directly and, in a Xa-dependent way, inhibits VII(a)/TF activity, presumably by forming a quaternary Xa/LACI/VII(a)/TF complex. Sequence analysis of complementary DNA clones has shown that LACI contains three tandemly repeated Kunitz-type serine protease inhibitory domains. To investigate the relationship between these Kunitz structures and LACI function, we have used site-directed mutagenesis to produce altered forms of LACI in which the residue at the active site cleft of each Kunitz domain has been individually changed. The second Kunitz domain is required for efficient binding and inhibition of Xa, and both Kunitz domains 1 and 2 are required for the inhibition of VIIa/TF activity; but alteration of the active-site residue of the third Kunitz domain has no significant effect on either function. We propose that in the putative inhibitory complex, Kunitz domain 1 is bound to the active site of VII(a)/TF and that Kunitz domain 2 is bound to Xa's active site. PMID- 2927511 TI - Conformational dynamics of individual DNA molecules during gel electrophoresis. AB - Gel electrophoresis is widely used in molecular biology to separate DNA molecules according to their sizes. The physical basis of this size separation is, however, poorly understood. Here we report observations of individual, fluorescently stained DNA molecules as they migrate during various kinds of gel electrophoresis. Their movement, under the influence of either a steady electric field or a pulsed-field, is characterized by cycles of elongation and contraction. Initially relaxed coils of DNA lengthen into 'hook-shaped' configurations which temporarily 'hang-up' on obstacles in the gel matrix before sliding off, contracting and entering another cycle. The effects of a new electrophoresis technique, termed 'pulse-oriented electrophoresis', which allows the effective angle of the electric field, and hence the molecular orientation of DNA, to be varied without electrode rearrangement, are also studied. In this case the DNA adopts a 'staircase' configuration showing that the net orientation in a direction is given by the vector sum of the pulses used. PMID- 2927512 TI - Lymphocyte differentiation. Not all in a name. PMID- 2927513 TI - Leucine zipper motif extends. PMID- 2927515 TI - Geriatric education: the Duke program. PMID- 2927514 TI - Patient acceptance and cleansing effectiveness of Golytely for colon surgery. PMID- 2927516 TI - Geriatric education programs in North Carolina. Response to the demographic imperative. PMID- 2927517 TI - Innovations in management. Choosing a vendor. PMID- 2927518 TI - Redesigning patient care to empower nurses and increase productivity. AB - Hospitals are being challenged to deliver inpatient care at lower costs due to declining net profit margins under fixed rate reimbursement. This 133-bed acute care facility integrated respiratory therapy and housekeeping within nursing in an effort to empower nurses while decreasing operational expenses. PMID- 2927520 TI - Executive summary of Secretary's Commission on Nursing Report. PMID- 2927521 TI - An interview with President Lucille Joel: perspectives from the American Nurses' Association (ANA). Interview by Carmella Bocchino. PMID- 2927522 TI - National League for Nursing survey of recent nurse grads dispels misconceptions about nursing shortage. PMID- 2927519 TI - Effectively structuring the interview process. PMID- 2927523 TI - [Developmental aspects in child psychiatry and child neurology]. PMID- 2927524 TI - [Mother was right; a misdiagnosed syndrome]. PMID- 2927525 TI - [Psychoanalytic thinking in current child psychiatry]. PMID- 2927526 TI - [The role of child and adolescent psychiatry in youth assistance]. PMID- 2927527 TI - [The care of foreign adopted children]. PMID- 2927528 TI - [Child and adolescent psychiatry in mentally retarded children and youths]. PMID- 2927529 TI - [Determining the diagnosis in children with autism and related contact disorders]. PMID- 2927530 TI - [Current developments in the treatment of autistic children]. PMID- 2927531 TI - [Learning and behavior problems in children with epilepsy]. PMID- 2927532 TI - [Dyslexia: practical aspects and implications]. PMID- 2927533 TI - [Early recognition and management of anorexia nervosa in adolescence]. PMID- 2927534 TI - [Depression in children and adolescents]. PMID- 2927535 TI - [Sequelae of skull injuries in children: complaints, behavioral changes and management]. PMID- 2927536 TI - [The use of psychopharmaceutical agents in children]. PMID- 2927537 TI - [The effect of anti-epileptics on the general functioning of children with epilepsy]. PMID- 2927538 TI - [Multidisciplinary management in a (semi)residential child psychiatric setting]. PMID- 2927539 TI - [The medical management of the mentally retarded child]. PMID- 2927540 TI - [Chronic intermittent volvulus of the stomach: difficult diagnosis, simple treatment]. PMID- 2927541 TI - [Side effects of drugs: assessment of causality]. PMID- 2927542 TI - [Monotherapy or combination therapy in severe bacterial infections?]. PMID- 2927544 TI - [The treatment of acute otitis media]. PMID- 2927543 TI - [Side effects of cytostatic agents; treatment recommendations]. PMID- 2927545 TI - [Measures for the prevention of puerperal mastitis]. PMID- 2927546 TI - [Is vitamin intake by the elderly in The Netherlands precarious?]. AB - The elderly are vulnerable to nutritional risks. The vitamin intake (assessed through dietary history) and vitamin status of 539 independently living persons aged 65-79 years and 44 lacto-(ovo)-vegetarian persons aged 65-97 years were evaluated. All respondents were apparently healthy. Compared with the Dutch recommended dietary allowances the intake of vitamins was assessed as adequate except for vitamin B6. The marginal intake of vitamin B6 is reflected in the vitamin B6 status. The prevalence of low 25-hydroxyvitamin D concentrations in plasma is high among elderly people as compared with younger adults (blood donors); the concentration is negatively correlated with age. The vegetarian elderly appeared to be at risk regarding the vitamin B12 status. In conclusion, the average intake of vitamins is assessed as adequate, whereas the intakes of vitamin B6 and vitamin D of Dutch apparently healthy elderly need more attention. PMID- 2927547 TI - [Intrauterine insemination in fertility disorders]. AB - The success of intrauterine insemination with in HAM-F10 washed spermatozoa was evaluated during a clinical study of two years, in 32 couples with male infertility, male and female infertility and unexplained infertility. Six women of the 16 treated couples with male infertility achieved pregnancy. In this group no spontaneous pregnancies occurred. In couples with male and female and unexplained infertility the usefulness of the treatment is not proven. Further careful evaluation is needed. PMID- 2927548 TI - [Release of the lateral retinaculum of the knee in retropatellar chondropathy]. AB - Retropatellar chondropathy is a frequent cause of pain in the knee; it usually runs a favourable natural course. When the symptoms interfere with work or sports, reduction of pain can be achieved by cleaving the lateral retinaculum (lateral release). To assess the results, a questionnaire was sent to 96 persons; 80 questionnaires could be evaluated. Only patients who had minor or no visible damage of the patellar cartilage were included in this study. Fifty-three patients reported improvement, in spite of which 34 had persistent mild symptoms which forced 12 of them to change the nature of their work. Thirty-seven patients had to change their sports activities in spite of the operation. PMID- 2927550 TI - [The discharge letter]. PMID- 2927549 TI - [NSAIDs: a clinical pharmacological role determination in the drug treatment of rheumatic disorders]. PMID- 2927551 TI - ['Typically atypical']. PMID- 2927552 TI - [Inhibitors of cholesterol synthesis: a welcome addition]. PMID- 2927553 TI - [Safety and efficacy of thrombolysis during ambulance transportation of patients with an acute heart infarct]. AB - We studied the safety and efficacy of thrombolytic therapy for acute myocardial infarction initiated prior to ambulance transport. Intravenous streptokinase with 5 X 10(5) IU (SK-i.v.) was started in 40 patients (group A) before transport and 36 patients (group B) after transport. In all patients immediate coronary angiography was performed, followed by intracoronary streptokinase. Infarct size was assessed from cumulative release of alpha-hydroxybutyrate dehydrogenase. No procedure-related complications were seen during transport. The time to SK-i.v. was 70 minutes in group A versus 125 minutes in group B. At first visualisation the infarct-related vessel was patent in 23 patients (58%) in group A and in 6 patients (17%) in group B (p less than 0.001). For anterior wall infarction we found a 32% smaller infarct size in group A (p less than 0.05). We conclude that SK-i.v. during ambulance transport is safe, increases early reperfusion and leads to a further reduction of infarct size which is significant in anterior wall infarction. PMID- 2927554 TI - [Experiences at a peripheral hospital with the intracoronary administration of streptokinase and urokinase in acute heart infarct]. AB - In 285 patients intracoronary fibrinolytic agents were administered 300 times during the acute phase of a myocardial infarction. The results and the complications of this therapy, as administered in a community hospital, did not differ from those obtained in a big randomized study performed by the Interuniversity Cardiological Institute of The Netherlands. Recanalization of a completely occluded coronary artery was obtained in 79% of the cases. Only 8.3% of the patients needed blood transfusion because of blood loss via the puncture in the femoral artery. No intracranial bleeding occurred. Actuarial total survival after 12 months was 90.5%. The incidence of recurrent myocardial infarction after successful intracoronary fibrinolytic therapy appears rather high; therefore, in some patient categories further therapy may be considered such as percutaneous transluminal coronary angioplasty or aortocoronary bypass surgery. PMID- 2927555 TI - [Efficacy and safety of simvastatin, a new cholesterol-lowering drug]. AB - The effects of simvastatin, an inhibitor of cholesterol synthesis, was studied in 50 patients with hypercholesterolaemia. In the first study, 24 patients with serum cholesterol levels of 10.74 +/- 1.59 mmol/l were treated with simvastatin 40 mg daily for 6 months. Serum cholesterol levels decreased within 4 to 8 weeks to stable values 30 to 36% below the basal value. Serum triglycerides decreased by 16 to 28% and high density lipoprotein (HDL) cholesterol increased by 6 to 11% on average. In the second study, 26 patients with serum cholesterol levels of 12.35 +/- 2.05 mmol/l were treated with simvastatin 40 mg daily as monotherapy or combined with a bile acid binding resin for 2 years. Cholesterol levels decreased to values which remained stable throughout the entire study period; after 2 years the decrease amounted to 43%. Compared with monotherapy, combination with a bile acid binding resin yielded a further 12% decrease of cholesterol. In the entire group, triglycerides decreased by 16% and HDL cholesterol increased by 9% on the average. Side effects were limited to slight increases in alanine aminotransferase and creatine phosphokinase occurring in some patients. Simvastatin appears to be an important asset in the treatment of hypercholesterolaemia. PMID- 2927556 TI - [Streptokinase in impending heart infarct]. AB - A patient is described with an impending myocardial infarction due to presence of an intracoronary thrombus in an otherwise normal left anterior descending artery. This case illustrates that intracoronary and intravenous administration of streptokinase can be of value in the treatment of impending myocardial infarction. PMID- 2927557 TI - [Osteogenesis imperfecta; treatment with internal splint for prevention of fractures]. PMID- 2927558 TI - [Pregnancy following 'early' menopause]. PMID- 2927559 TI - [Pharmacotherapy during pregnancy and lactation]. PMID- 2927560 TI - [Taking one's own blood pressure]. PMID- 2927561 TI - [Use and abuse of the sphygmomanometer]. PMID- 2927562 TI - [Acceleration in aviation]. PMID- 2927563 TI - [Incidence of kidney function deficiency in 2050 patients admitted to a general hospital; a prospective study]. PMID- 2927564 TI - [Cardiologic disorders in patients with Lyme borreliosis]. PMID- 2927565 TI - Percutaneous fine needle aspiration biopsy in the early diagnosis of pancreatic carcinoma. PMID- 2927566 TI - Criminalization of medicine. PMID- 2927567 TI - Another point of view--C-section rates. PMID- 2927568 TI - Patient-controlled analgesia. AB - Patient-Controlled Analgesia is a new method of narcotic delivery. It allows titration of analgesic drugs to the individual patient's requirements. It provides superior pain relief for many patients, minimize narcotic side effects and reduces patients' dependence upon nursing personnel for their pain relief. It may shorten postoperative recovery time and decrease hospital length of stay. At a time when physicians and hospitals are feeling compelled to hasten patients' recovery and still provide good quality of care, Patient-Controlled Analgesia may be an excellent way to accomplish both goals. PMID- 2927570 TI - Nursing supply in Nebraska. PMID- 2927569 TI - Nurse education plan. PMID- 2927571 TI - Nurses endorsing transplantation. PMID- 2927572 TI - The National League for Nursing. PMID- 2927573 TI - Sigma Theta Tau--what is it? PMID- 2927574 TI - The image of nursing. PMID- 2927575 TI - RCT update. PMID- 2927576 TI - RNs needed in nursing home setting. PMID- 2927577 TI - The role of dopaminergic pathways in thermoregulation in the rabbit. AB - Dopamine, when injected into the anterior hypothalamus of the rabbit, induced a slight hyperthermia due to an upward shift of the threshold central temperature for induction of cold thermogenesis, panting and vasodilation. A slightly reduced thermosensitivity of the controller regulating vasodilation may also contribute to the hyperthermic effect of dopamine. Intrahypothalamic injections of the dopamine agonist, apomorphine, induced a similar effect to that of dopamine, with the exception that the thermosensitivity of the controller regulating vasodilation was not changed. Intraperitoneal injections of a dopamine antagonist, haloperidol, induced a marked hypothermia, due to a downward shift of the threshold central temperature for induction of cold thermogenesis, panting and vasodilation. A slightly reduced thermosensitivity of the controller regulating vasodilation was also observed. Intrahypothalamic injections of haloperidol did not induce an antagonist effect to dopamine, but rather tended to induce hyperthermia. Thermoregulatory responses, occurring after administration of dopamine or apomorphine, partially resembled those seen after administration of neurotensin or prostaglandins. PMID- 2927578 TI - Age-related alterations in cardiovascular responsiveness to clonidine infused into the nucleus tractus solitarii in rats. AB - The cardiovascular response to the unilateral injection of clonidine into the nucleus tractus solitarii in old compared to young rats was evaluated. In 3-month old rats clonidine (0.25, 0.5 and 1 microgram) injected into the nucleus tractus solitarii in anaesthetized rats produced a significant fall in blood pressure (BP) and a significant decrease in heart rate (HR). In contrast, in 12 month old rats the maximum fall in blood pressure and heart rate was significantly less than in young animals. In addition, in older rats (24 month old) clonidine, at the same or larger doses given into the nucleus tractus solitarii did not produce any significant change in the cardiovascular parameters studied. In conclusion, the present experiments provide evidence that during ageing there is a progressive decrease in the cardiovascular response to alpha 2-adrenoceptor stimulation in the nucleus tractus solitarii. In addition, it is conceivable that such a decrease and subsequently the lack in response may be related to a progressive decrease in the number and/or affinity of the specific alpha 2 adrenoceptor binding sites at this level. PMID- 2927579 TI - The effects of kynurenic acid, quinolinic acid and other metabolites of tryptophan on the development of the high pressure neurological syndrome in the rat. AB - The effects of some biologically active metabolites of tryptophan on the high pressure neurological syndrome (HPNS) were studied. Kynurenic acid, quinolinic acid, 5-hydroxytryptophan, kynurenine and 3-hydroxyanthranilic acid, at doses within the physiological range, were administered exogenously to rats prior to exposure to increased pressure and any effects on the tremor, myoclonus and convulsion end points of the high pressure neurological syndrome were observed. Quinolinic acid (25 and 50 mg/kg) and kynurenine (50 mg/kg) reduced the onset pressure for tremor, but not myoclonus or convulsions. Kynurenic acid (100 mg/kg) increased tremor onset pressure; 5-hydroxytryptophan (20 mg/kg) slightly increased onset pressure for tremor but decreased that for myoclonus. 3 Hydroxyanthranilic acid (20 mg/kg) had no significant effect on any of the motor signs of the syndrome. These data provide further support for the idea that the motor events seen in the high pressure neurological syndrome are not produced by a single mechanism. Differences between the responses to related metabolites suggest that the precise balance between compounds such as kynurenic acid and quinolinic acid may be important in the appearance of the high pressure neurological syndrome. PMID- 2927580 TI - Effect of trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidin) cyclohexyl] benzeneacetamide (U-50,488H), a kappa opioid receptor agonist, on intake of food in food-deprived and non-deprived spontaneously hypertensive and normotensive Wistar-Kyoto rats. AB - The effect of U-50,488H, a selective kappa opioid receptor agonist on the intake of food in food-deprived and non-deprived spontaneously hypertensive and normotensive Wistar-Kyoto rats was determined. In food deprived Wistar-Kyoto rats, intraperitoneal administration of U-50,488H, produced a bell-shaped curve on the intake of food, consistent with earlier reports in the literature. Thus, at a dose of 0.1 mg/kg there was a significant increase in the intake of food and at 10 mg/kg it caused a decrease in the intake of food, at 2, 4 and 6 hr after the treatment with drug. The amount of food consumed at each dose and the time interval was greater in hypertensive rats than in Wistar-Kyoto rats. Similar effects were produced when the animals were not deprived of food. The basal intake of food in the two strains of rats did not differ. The results indicate a greater sensitivity of spontaneously hypertensive rats to kappa opioid receptor agonists and further the previous observations that compared to Wistar-Kyoto rats, the hypertensive rats have a greater density of central kappa opioid receptors. PMID- 2927581 TI - Effect of morphine on far-field somatosensory evoked potentials in the rat. AB - Far-field somatosensory evoked potentials were obtained by electrical stimulation of the volar surface of the forepaw and were recorded from the skull overlying the contralateral somatosensory area of the cerebral cortex. Three distinct peaks were discernable in the somatosensory evoked potentials prior to the first cortical component. Effects of different doses of morphine (0.5, 1.0, 2.5 and 5.0 mg/kg body weight), administered intravenously, were studied. Morphine selectively reduced the amplitude of component III in a dose-dependent manner. The maximum effect was obtained at a dose of 2.5 mg/kg. This effect was reversed within 2 min by intravenous administration of naloxone (0.25 mg/kg). The amplitudes of peaks I and II and the latencies of components I, II and III were not significantly affected by morphine. Infusion of morphine (25 micrograms/kg) into the thalamus showed effects on the far-field somatosensory evoked potentials similar to the maximal effect obtained on intravenous infusion. Therefore, the action of morphine on somatosensory evoked potentials could be attributed to its effect on the thalamic neurones. PMID- 2927582 TI - Perinatal treatment with glucocorticoids and the risk of maldevelopment of the brain. AB - Drugs administered during the perinatal period reach the developing organism at the vulnerable stage of intensive brain histogenesis and cytodifferentiation. They may interfere with the programme of developmental processes in the brain and lead to disturbances at the cellular/subcellular level and to biochemical alterations. These abnormalities form the basis for the functional pathology which becomes apparent gradually during maturation or even in adulthood as neuropsycho-behavioural deviations. A model experimental study in rats was carried out with synthetic glucocorticoids, which are widely used in obstetrics and neonatology for the prevention and treatment of neonatal idiopathic respiratory distress syndrome. As the developmental stage of the brain of the human foetus in late pregnancy closely resembles the ontogenetic phases of the brain of the rat in the early postnatal period, the neonate rat was taken as a model. The administration of dexamethasone to 7-day-old rats resulted in significant depletion of glucocorticoid receptors from the cytosol of the brain in a dose-dependent manner, beginning with the dose of 0.04 mg/kg (s.c.), i.e. a dose one order lower than the clinical dose used in obstetrics (0.4-0.5 mg/kg). Long-term follow-up of a single neonatal injection of dexamethasone (0.2 or 1 mg/kg s.c. on postnatal day 7) revealed an acceleration of some developmental landmarks in the preweaning period (incisor eruption, eye opening, motor skill) on the one hand, but a retardation of body growth and vaginal opening on the other hand. Adult animals exhibited a deficit in motor co-ordination, behavioural deviations (hyperactivity with stereotypy, decreased adaptability, increased emotional reactivity) and disturbances in reproduction in both males and females.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2927583 TI - Effect of pretreatment with amphetamine on the interaction between amphetamine and dopamine neurons in the nucleus accumbens. AB - The present study was designed to examine the effect of pretreatment with amphetamine on the ability of amphetamine to release dopamine from slices of the nucleus accumbens and striatum and to stimulate locomotor activity or stereotyped behavior, after direct injection into either the nucleus accumbens or the striatum. Rats were injected twice daily for 5 days with either amphetamine (5 mg/kg, i.p.) or saline. At 33 days after this pretreatment, the release of endogenous dopamine from both regions of the brain in vitro by amphetamine and the changes in behavioral responses to the direct injection of amphetamine into either region were examined. Amphetamine at both 1 and 10 microM stimulated the release of endogenous dopamine from slices prepared from both of the brain areas. The release of dopamine by amphetamine was increased in rats pretreated with amphetamine. Consistent with its ability to stimulate endogenous release of dopamine, amphetamine, when injected into the nucleus accumbens, stimulated locomotor activity, while stereotyped behavior was enhanced when amphetamine was injected into the striatum. However, the locomotor activity and stereotyped behavioral responses to small doses of amphetamine (5, 10 or 25 micrograms) were not significantly greater in amphetamine-pretreated rats, compared to saline pretreated animals. A greater stimulation of both responses in amphetamine pretreated rats was only observed when a large dose (50 micrograms) of amphetamine was administered into either the nucleus accumbens or striatum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2927584 TI - Familial cavernous angioma of the brain stem dominantly inherited in Hispanics. AB - A 23-year-old Hispanic woman whose mother had died of a brain hemorrhage developed signs and symptoms of a brain stem lesion. These gradually progressed over the next 30 years. Her computed tomographic and magnetic resonance imaging scans show features typical of a cavernous angioma in the brain stem. Her daughter had a transient right hemiparesis at age 25, and at age 28 noted periorbital pain with twitching of the forehead and jaw. The daughter's computed tomographic and magnetic resonance imaging scans likewise suggest cavernous angioma of the brain stem. There has been only one other report of familial cavernous angioma of the brain stem, and that also involved a Hispanic family. Hispanics have a known predisposition to familial cavernous angioma, and this diagnosis should be considered when more than one person in a family develops brain stem symptoms. PMID- 2927585 TI - Intrasellar balloon inflation for treatment of symptomatic empty sella syndrome. AB - Intrasellar extradural placement of a detachable vascular balloon via a transsphenoidal approach was performed successfully in a patient with primary empty sella syndrome, relieving headache and visual field defect. This technique offers an alternative approach to other methods of treating symptomatic empty sella syndrome that require packing of the sella with fat, muscle, cartilage, or bone. PMID- 2927586 TI - Kluver-Bucy syndrome in a child with bilateral arachnoid cysts: report of a case. AB - Kluver-Bucy syndrome is an uncommon constellation of behavioral abnormalities resulting from bilateral temporal lobe damage. The syndrome is rare in adults and even less commonly seen in children. In this paper we present a child with Kluver Bucy syndrome and bilateral temporal arachnoid cysts. PMID- 2927587 TI - Lumbar synovial cysts: report of eleven cases. AB - Over the past 18 months we have encountered 11 cases of symptomatic lumbar synovial cysts. This experience occurred during a period during which some 1,800 lumbar computed tomographic scans were done. The apparent increased incidence of these lesions is most likely due to the increased diagnostic ability made possible by the advent of high-resolution computed tomography and magnetic resonance imaging. This is a report and discussion of our 11 cases with a review of the literature. There is nothing distinctive in the physical findings or in the histories of our patients, but we have found, as have others, that high resolution computed tomographic scanning and magnetic resonance imaging significantly enhance the diagnosis of such lesions. PMID- 2927588 TI - Cordectomy for syringobulbo-myelia with sleep apnea secondary to a spinal extramedullary tumor: case report. AB - The case of a 40-year-old man with syringobulbo-myelia secondary to an unresectable spinal extramedullary tumor is described. Fifteen years previously, the patient had undergone a laminectomy of T8 through T12 for a "benign" spinal cord tumor at another hospital and had become paraplegic; the tumor (neurinoma) had been neglected for 12 years. Magnetic resonance imaging demonstrated a large thoracolumbar spinal tumor with syringobulbo-myelia. Polysomnography showed central-, peripheral-, and mixed-type sleep apneas. After the failure of an attempted syringoperitoneal shunt, cordectomy at the level of T6 was performed with a good result. The mechanisms of the formation of syringomyelia and sleep apnea secondary to a caudal spinal extramedullary tumor are discussed. PMID- 2927589 TI - Surgery of petroclival meningiomas: report of 24 cases. AB - Twenty-four patients with petroclival meningiomas were operated upon at the neurosurgical clinic of the City Hospital of Hannover between 1978 and 1987. Seventeen were women and seven men; the mean age was 45 years. Symptoms were usually present for more than 2 years before the diagnosis was made. The most common symptom was disturbance of gait; the most common preoperative sign was cranial nerve deficit, mainly of the 7th and 8th nerves. Preoperative neuroradiological evaluation included computed tomography and four-vessel cerebral angiography. Fifteen patients (62%) had a tumor larger than 2.5 cm in its major diameter. The surgical approaches used were the retromastoid, pterional, subtemporal, and combined retromastoid-subtemporal. We developed a modification of the retromastoid-subtemporal approach with preservation of the transverse sinus and used this in the last 2 patients. There was no postoperative death; 11 patients (46%) suffered postoperative complications, mainly in the form of cranial nerve deficits, often reversible. "Total" tumor removal was achieved in 17 patients (71%). Twenty patients (83%) were independent at the time of discharge from the hospital. With accurate neuroradiological evaluation, careful choice of the surgical approach, and sound application of microsurgical techniques, petroclival meningiomas may be "totally" and safely resected in a significant number of patients. PMID- 2927590 TI - Granulocytic sarcoma presenting as an epidural mass with cord compression. AB - Granulocytic sarcoma (GS) usually occurs during the course of, or as a presenting sign of myelogenous leukemia. Rarely it is found before peripheral blood or bone marrow evidence of leukemia is present. We describe a man who presented with low back pain and lower extremity weakness. He had spinal cord compression due to GS without evidence of leukemia. Only four such instances have been previously reported. Such aleukemic presentations of GS are frequently misdiagnosed. The chloroacetate esterase stain and electron microscopy are useful in demonstrating the myeloid origin of GS cells. GS lesions are probably best treated by localized radiation therapy and systemic chemotherapy. PMID- 2927591 TI - Intraoperative ventricular puncture. PMID- 2927592 TI - Papillary ependymoma of the cervical spinal cord. PMID- 2927593 TI - Upward-gaze palsy due to shunt malfunction. PMID- 2927594 TI - Surgical management of extreme lateral lumbar disc herniations. PMID- 2927595 TI - Surgical treatment of intracavernous neoplasms: a four-year experience. AB - Forty-two patients with neoplasms involving the cavernous sinus had operations between 1983 and 1987. The lesions included 25 benign tumors (e.g., meningioma, neurilemoma) and 17 malignant tumors (e.g., chondrosarcoma, adenoid cystic carcinoma). The cavernous sinus was entered by inferior, anterolateral, or medial extradural approaches or by superior or lateral intradural approaches. The intracavernous internal carotid artery was managed by dissecting tumor away from it or by occlusion and excision with or without direct vein graft reconstruction, based on the results of a preoperative balloon occlusion test. Cranial nerves III, IV, V, and VI usually were dissected from tumor, but in 3 cases of tumor invasion, the excised nerve segment was reconstructed by direct suture or with a sural nerve interposition graft. Twenty-one of the benign tumors and 8 of the malignant tumors were excised totally and the remainder subtotally. On follow-up ranging from 3 to 48 months, one subtotally excised meningioma recurred and was treated with re-excision and adjuvant radiation therapy. Two "totally" excised malignant tumors recurred outside the cavernous sinus at the margins of excision. There was no operative mortality or permanent cerebral morbidity. Postoperatively, the ocular and neurological function of most patients was similar to the preoperative status; in some, it was significantly improved. Thirteen additional patients with intracavernous neoplasms also were evaluated during the same period and followed without operation. The early follow-up information regarding these patients is provided. PMID- 2927596 TI - Determinants of head injury mortality: importance of the low risk patient. AB - Data were obtained prospectively for 7,912 head-injured patients admitted from 1980 to 1981 to 41 hospitals in 3 U.S. metropolitan areas. Highly significant independent predictors of mortality were motor score, number of reactive eyes, systolic blood pressure, abdominal injury, chest injury, age, and hospital unit (hospital or group of hospitals). The difference between the number of deaths observed and the number expected, by hospital unit, ranged from 43% below expectation to 52% above expectation. The 2 hospital units with the lowest mortality had only 1 death, where 9.4 would be expected, in patients whose risk of death was estimated to be less than 10%. In the single hospital with clearly excess mortality, however, the standardized mortality ratios were 208, 135, and 144% for the risk groups whose probabilities of death were 0 to 50, 50 to 80, and 80 to 100%, respectively. The lack of deaths in those hospitals with the best mortality experience and the excess mortality in the hospital with the worst mortality experience appear to be explained largely by differences in patients who, by clinical criteria, seem to be at low risk for death, and not by severely injured patients. PMID- 2927597 TI - Transoral approach to extradural lesions of the lower clivus and upper cervical spine: an experience of 19 cases. AB - An experience with 19 cases of transoral exposure of the lower clivus and ventral aspect of the upper cervical spine is presented. The spectrum of pathological entities in this series includes malformative, neoplastic, and spondylotic conditions. The report is designed to focus upon some points of overall surgical management of patients treated by the transoral approach, with emphasis on management of postoperative instability, and to underline the discrepancy in the prognosis of congenital and acquired disorders, in terms of mortality, morbidity, and long-term results. PMID- 2927598 TI - Craniopharyngiomas: fluctuation in cyst size following surgery and radiation therapy. AB - Patients with craniopharyngiomas who demonstrate cyst enlargement after surgery and radiation are often presumed to be treatment failures. Therapeutic approaches in various centers include repetitive cyst aspirations, surgical reexcision, and installation of cytotoxic agents such as methotrexate, 32P, or 198Au. Each intervention has associated severe or even lethal side effects. Not all patients with craniopharyngioma who have cystic enlargement after primary therapy require an intervention, as demonstrated by 4 patients recently managed in the University of Rochester Medical Center. Since 1978, when computed tomography was routinely in use, we have managed 11 patients with craniopharyngiomas who were treated with surgery followed by radiation therapy. Three of these patients demonstrated post irradiation enlargement of the residual cystic component followed by a decrease in size without surgical intervention. An additional patient showed cystic growth followed by stabilization of size. It is noteworthy that the cyst enlarged within the first 5 months after radiation therapy in the 3 patients who subsequently demonstrated a diminution in the size of their cysts. This suggests that the mechanism for cyst formation remained intact and subsequently abated because of a radiation-induced lesion. We conclude that after treatment with surgery and radiation therapy, the cystic component of craniopharyngiomas may increase and, without intervention, subsequently decrease in size. Thus, in the asymptomatic patient who demonstrates cystic growth soon after primary therapy, close observation alone may be warranted. PMID- 2927599 TI - Distribution of 10B after infusion of Na210B12H11SH into a patient with malignant astrocytoma: implications for boron neutron capture therapy. AB - If a sufficient concentration of the stable isotope 10B is introduced into a neoplasm, radiation therapy can be effected by short-range heavy charged particles from the disintegration of 10B by slow neutrons. Brain tumors were irradiated postoperatively by Hatanaka and co-workers in Japan using a 1 to 2 hour intraarterial infusion of 10B-enriched Na2B12H11SH (Na210B12H11SH) before exposure of the tumor-bearing area of the brain to slow neutrons from a 100 kilowatt nuclear reactor. The clinical outcome of such boron neutron capture therapy has been favorably impressive in some patients, but its efficacy in brain tumors needs improvement. In our study, a terminally ill patient with malignant astrocytoma was infused intravenously with Na210B12H11SH for 25 hours. The postmortem distribution of 10B in unfixed, frozen, tumor-bearing brain and spinal cord tissues was studied by comparing representative cryostat sections of these specimens with neutron-induced heavy charged particle radiographs of the same sections. Preferential accumulation of 10B was observed in the tumor, with relatively little accumulation of 10B in the parenchyma of the central nervous system. PMID- 2927600 TI - Nitrous oxide suppresses the electromyographic response evoked by electrical stimulation of the motor cortex. AB - The influence of nitrous oxide on motor evoked potential (MEP) elicited in rats by cortical and midcervical electrical stimulation was studied and compared with early components of somatosensory evoked potential (SEP) following stimulation of the posterior tibial nerve in 6 rats. We found that nitrous oxide gradually suppresses MEP, depending on the concentration of this inhalation agent. At a concentration of 66 vol% of nitrous oxide, the MEP was completely abolished, whereas the initial component N1-P1 of the SEP was only slightly reduced. We conclude that the descending impulse elicited by electrical stimulation of the corticospinal tract is mainly inhibited at the level of the spinal neuronal or interneuronal system, since (1) neuromuscular transmission is not blocked by nitrous oxide, and (2) MEP suppression is the same following cortical and midcervical stimulation. PMID- 2927601 TI - Angiographic follow-up study of cerebral arteriovenous malformations with reference to their enlargement and regression. AB - Twenty patients with cerebral arteriovenous malformations (AVMs) were followed up by angiography. Of the 20 AVMs, 16 were nontreated and the remaining 4 were residual. The follow-up periods between the two examinations were from 5 to 28 years, with a median interval of 15 years. At follow-up, the size of the AVM had increased in 4 patients (20%), decreased in 4 (20%), totally regressed in 4 (20%), and was unchanged in 8 (40%). In cases of enlarged AVMs, the patients were all young: from 0 to 11 years old at first angiography and from 6 to 30 at second angiography. The decrease or total regression of the AVM occurred in older patients (over 30 years old at second angiography), and the AVMs were relatively small and fed by single or a few feeders. The patient's age and the size of AVM should be considered when operative indications are discussed. PMID- 2927602 TI - Intracranial arteriovenous malformation: relationship between clinical factors and surgical complications. AB - Serious morbidity and hyperemic states continue to complicate the treatment of certain intracranial arteriovenous malformations (AVMs). Clinical and radiographic characteristics of 62 patients treated over 3 years were analyzed to determine if hyperemic complications (HCs) (defined as unusual perioperative edema or hemorrhage) and outcome could be predicted. Twenty-five (40%) of the patients were less than 30 years old, 28 (45%) were between 30 and 50, and 9 (15%) were more than 50. A history of hemorrhage was found in 48%, and 34% presented with progressive deficits. Thirteen (21%) developed evidence of HCs; 51 (82%) ultimately had a good outcome, 4 (6%) had a poor outcome, and 7 (11%) died. The incidence of HCs was higher in patients whose AVMs recruited perforating vessels (53%) than those without (7%) (P less than 0.001). The presence of preoperative angiographic steal carried a 35% risk of HCs whereas its absence carried a 13% risk (P less than 0.05). The sum of the diameters of the feeding vessels was also predictive (P less than 0.05). Outcome was clearly age-related: good outcome was achieved in 92% of the patients less than 30 years old, 86% of those 30 to 50, and 44% of patients older than 50 (P less than 0.05). Left hemispheric AVMs showed less morbidity than right (P less than 0.05) as did those without perforating vessel recruitment (P less than 0.07). HCs had a dramatic impact on outcome with 92% of patients without HCs having good outcome and 46% of those with HCs recovering well (P less than 0.001). PMID- 2927603 TI - Improvement of cortical perfusion, intracellular pH, and electrocorticography by nimodipine during transient focal cerebral ischemia. AB - The alterations in metabolism and cerebral blood flow that occur following transient focal ischemia were studied in rabbits anesthetized with halothane and subjected to transient occlusion of an M2 segment of the middle cerebral artery (MCA). The parameters measured included intracellular brain pH and focal cortical blood flow (fCBF)--assessed by the umbelliferone technique--electrocorticograms, and cortical microcirculatory changes. A gradient of ischemia developed in the cortex between the patent and occluded vessels. Cortical sites with moderate and severely diminished flow were examined as a function of time before and after occlusion. Mean preocclusion fCBF was 50.8 +/- 2.1 ml/100 g/min, and brain pH was 6.99 +/- 0.04. Following occlusion, fCBF fell to 14.6 +/- 2.3 ml/100 g/min, with an intracellular pH of 6.53 +/- 0.03 in sites of severe ischemia in the territory of the occluded vessel. Sites between the patent and occluded branches revealed moderate changes in fCBF and intracellular pH of 26.7 +/- 3.6 ml/100 g/min and 6.74 +/- 0.03 ml/100 g/min, respectively. Sites adjacent to the patent M2 branch remained similar to baseline. Pretreatment intravenously with nimodipine, a dihydropyridine class of Ca2+ channel antagonist, improved flow in the territory of the occluded segment of the middle cerebral artery to 30.6 +/- 2.2 ml/100 g/min, while maintaining the brain pH at 6.83 +/- 0.03. Similarly, at sites intermediate between the patent and occluded M2 segments of the MCA, cortical blood flow remained at 53.5 +/- 4.0 ml/100 g/min, and the pH at 6.95 +/- 0.04, in 10 animals pretreated with nimodopine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2927604 TI - Acute effect of the Nd:YAG laser on the cerebral arteriovenous malformation: a histological study. AB - The acute effect of Nd:YAG laser beam on cerebral arteriovenous malformations (AVMs) was examined. Histological examination of the specimens after treatment with the Nd:YAG laser revealed that the most prominent effect of the laser was shrinkage of the collagen of the vessels of the AVM, which led to laser-induced narrowing of blood vessels. The brain tissue confined to the resected AVM did not contain any histological evidence of acute damage. The resection of 10 cases of AVMs was safely accomplished with no morbidity or increased neurological deficits attributable to the laser technique. PMID- 2927606 TI - Selective shunting during carotid endarterectomy based on two-channel computerized electroencephalographic/compressed spectral array analysis. AB - The reliability of selective shunting based on computerized electroencephalographic (EEG) monitoring has not been addressed. In this study, 103 carotid endarterectomies were performed with selective shunting based on a two-channel computerized EEG monitor that processed the on-line, raw electroencephalogram (EEG) to produce a compressed spectral array (CSA). Ischemic EEG events were identified by amplitude attenuation of the raw EEG and/or loss of high-frequency activity on the CSA. Fourteen patients (13.6%) received a bypass shunt, and postoperative neurological examinations showed 97 patients (94.2%) to be intact. A correlation between total (cumulative) ischemic EEG time and the postoperative neurological exam was demonstrated (P less than 0.0001). Six postoperative deficits (5.8%) occurred, five in patients whose computerized EEGs demonstrated an ischemic EEG event late during carotid clamping, when it was no longer possible to place a shunt. The sixth deficit was found in a patient whose EEG did not demonstrate any patient whose EEG did not demonstrate any signs of cerebral ischemia. Five of these six new deficits resolved within 12 hours, and only one persisted for 72 hours, when the patient died of a pulmonary embolism (cerebral infarction and mortality rate of 1%). These results appear to demonstrate that two-channel monitoring of both the CSA and the unprocessed (raw) EEG simultaneously can be used as a reliable indicator of whether a bypass shunt is required during carotid cross-clamping in all patients, regardless of their preoperative neurological history or angiographic findings. PMID- 2927605 TI - Early carotid endarterectomy after cerebral infarction. AB - The objective of the study was to review our recent experience with carotid endarterectomy performed within 30 days of completed cerebral infarction and to evaluate the role of computed tomographic (CT) scanning in the decision-making process. Twenty-seven of 302 operations (9%) were carried out during the 30-day time period. The mean interval between cerebral infarction and surgery was 14 days. Angiography revealed severe stenosis (greater than 75%) of the internal carotid artery in 19 patients. Severe stenosis with deep ulceration found in 6 patients and moderate stenosis (i.e., 50-75%) with deep ulceration was found in 2 patients. CT scans showed recent infarction in 4 patients and an old subcortical lacune in 2 patients. Twenty-two patients were neurologically stable with mild deficits and showed normal results on a CT scan performed 24 hours or more after the ischemic event. These patients underwent early cerebral angiography and carotid endarterectomy without permanent morbidity or mortality. Two patients with moderate stable neurological deficits and findings of recent infarction on CT scans had uneventful postoperative courses. Five patients who were neurologically unstable underwent surgery. The 2 patients with repeated transient ischemic attacks and normal findings on CT scans had uneventful postoperative courses. Two of the three patients with progressive neurological deficits and CT findings of recent cerebral infarction experienced extension of their infarcts after surgery. One of these patients died. Our personal experience, together with a review of previous reports, indicated that patients who have minimal residual neurological deficits and whose CT scans show normal findings are at low surgical risk, perhaps approaching that of patients with transient ischemic attacks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2927607 TI - Use of intraoperative ultrasonography to improve the diagnostic accuracy of exploratory burr holes in patients with traumatic tentorial herniation. AB - Seventeen head-injured patients with signs of brain stem compression at admission underwent emergency bilateral burr-hole exploration before computerized tomographic (CT) scanning. After exploration of the epidural and subdural spaces, real-time ultrasonography was performed intraoperatively to identify intraaxial hematomas. Epidural or subdural hematomas were identified surgically in 11 patients (65%) and immediately evacuated through a craniotomy; in 2 patients, bilateral subdural hematomas were removed. Ultrasonography showed no evidence of intracerebral mass lesions in 14 (82%) of the 17 patients, demonstrated extensive contusions of the temporal lobe in 2 patients (prompting partial lobectomy in both cases), and revealed a small intraparenchymal hematoma deep within the dominant hemisphere, which was not removed, in 1 patient. The sensitivity of ultrasound images for identifying intraparenchymal lesions was evaluated postoperatively by CT or autopsy. In 15 patients (88%), the results of ultrasonography were confirmed. In 2 (12%), CT scans showed small but significant lesions at the frontal pole missed by ultrasonography; one patient had a residual subdural hematoma, and the other a small intraparenchymal hemorrhage. These results confirm that patients with clinical evidence of brain stem compression soon after head injury often have extraaxial hematomas that can be readily identified by burr-hole exploration. Although intraparenchymal hematomas are rare immediately after head injury, they can usually be identified by intraoperative ultrasonography. This simple technique can reduce the risk of missing intracranial hematomas during emergency burr-hole exploration and improve intraoperative decision making in this population of severely head-injured patients. PMID- 2927608 TI - Erroneous measurement of intracranial pressure caused by simultaneous ventricular drainage: a hydrodynamic model study. AB - Intracranial pressure (ICP) is often measured from intraventricular catheters, a technique that allows therapeutic drainage of ventricular cerebrospinal fluid (CSF) as an aid in controlling ICP and circumventing obstruction. Drainage of CSF simultaneously with ongoing ICP measurement has been advocated as safe and efficient, and devices are commercially available to permit this practice; however, this concept has been seriously challenged, based on clinical observations. The inaccuracy induced by simultaneous CSF drainage and ICP monitoring is quantitated in this report in a mechanical brain model using a standard ventricular catheter. The following conclusions have been confirmed: 1) rapid CSF drainage induces a severe artifactual reduction in measured ICP, more extreme at higher pressures; 2) calibrated slower rates of CSF drainage produce a severe, although less immediate, reduction in measured ICP; 3) severe artifact appears even in the presence of continuous CSF outflow, so a system that measures ICP only in the presence of CSF flow does not prevent artifact; 4) with simultaneous CSF drainage, measured ICP is determined more by the outflow pressure setting than by actual brain pressure; 5) Since ICP elevation of 25 to 30 mm Hg blocks CSF production, even slow fluid drainage at high pressures should ultimately lead to ventricular collapse and severe artifact. PMID- 2927609 TI - Cognitive outcome and quality of life one year after subarachnoid haemorrhage. AB - In this prospective study, 100 patients with subarachnoid haemorrhage (SAH) were assessed at discharge, 3 months, and 1 year using modern methods of neuropsychology to examine cognitive status and semistructured interviews to assess changes in personality and quality of life. A control group of 50 patients suffering myocardial infarction were also assessed at discharge and 1 year. Results of cognitive testing in the SAH group were unremarkable and compared well with the control group. Similarly, there was no evidence of a consequent reduction in the quality of life in the majority of the SAH patients. These results lead us to conclude that where the medical and surgical course of SAH is uncomplicated, patients recover with no permanent or significant reduction in their intellectual ability of life status. Possible reasons for the difference between these results and those of other studies are discussed. PMID- 2927610 TI - Determination of irreversible ischemia by xenon-enhanced computed tomographic monitoring of cerebral blood flow in patients with symptomatic vasospasm. AB - In patients with subarachnoid hemorrhage, delayed neurological deficits, often followed by infarction, are believed to result from ischemia caused by vasospasm. Cerebral blood flow (CBF) data have been useful in predicting the risk of vasospasm in these patients and in distinguishing those deficits caused by vasospasm. Although CBF thresholds for infarction have been established in animals, few clinical studies have correlated CBF values with neurological symptoms and infarction. To assess the sensitivity to ischemia provided by xenon enhanced computed tomography (Xe/CT) of CBF and to define the clinical significance of specific values that it measures, we compared the clinical, CT, and Xe/CT findings on CBF in 51 patients with subarachnoid hemorrhage caused by ruptured aneurysms. Each patient had 1 to 6 Xe/CT studies. Fourteen patients had symptomatic vasospasm. In all 14, the first post deficit Xe/CT study found abruptly reduced CBF, either regionally or globally. In 9 of these 14 patients, flow values fell below 15 ml/100 g/min in 2 or more adjacent 2-cm cortical regions of interest, and in all 9, concurrent follow-up CT scans showed infarction in these regions. Eight of the 9 had paralysis and a severe sensory deficit. No patient whose CBF remained above 18 ml/100 g/min developed infarction. The blood flow studies caused neither significant complications nor neurological deterioration. The Xe/CT CBF method appears very sensitive to the early detection of symptomatic vasospasm. In most patients with subarachnoid hemorrhage, this noninvasive technique can replace angiography to delineate the location and severity of vasospasm, and may be useful in predicting the development of infarction. PMID- 2927611 TI - Surgical treatment of tumors in the anterior skull base using the transbasal approach. AB - Five patients with tumors in the anterior skull base were surgically treated using the transbasal approach, which permits removal of the tumor, repair of the dura mater, and reconstruction of the skull base in a one-stage procedure. By using autologous materials for the bone graft and pedunculated pericranial flap for the reconstruction, the intracranial structures are separated from the air filled nasal and paranasal cavities. No postoperative complications such as wound infection and leakage of cerebrospinal fluid were encountered. The use of this surgical technique makes it possible to extirpate brain tumors that heretofore have been considered unresectable. PMID- 2927612 TI - An orbitocranial approach to complex aneurysms of the anterior circulation. AB - A surgical approach to the skull base was developed in cadavers and then used in the treatment of patients with complex aneurysms of the anterior circulation. The operative method involves removal of portions of the orbital rim, orbital roof, and sphenoid bone. By removing the orbital rim and a portion of the orbital roof, multidirectional viewing is possible. This is important when dealing with the anterior aspect of the cavernous sinus and anterior clinoid process, as must frequently be done when isolating the neck of an ophthalmic aneurysm. The optic canal is opened wide and the optic nerve mobilized, allowing resection of the dura propria covering the cavernous carotid artery. Clip placement is performed in an anteroposterior plane, thus lessening the chance for compromise of the internal carotid artery. The low approach alleviates brain retraction and the small flap minimizes brain exposure. The approach also allows preservation of the arterial and neural supply to the frontalis and temporalis muscles, thereby preventing postoperative cosmetic deficits. During the past year and a half, this approach has been employed in 25 patients with difficult aneurysms of the anterior circulation. The difficulties of these cases stemmed from their odd location, size, or complex anatomy. Although periorbital edema may have been more severe during the first postoperative week, overall improved cosmesis was achieved. PMID- 2927613 TI - Outcome of laminectomy for civilian gunshot injuries of the terminal spinal cord and cauda equina: review of 88 cases. AB - Case records of 88 patients with low-velocity gunshot injuries of the terminal spinal cord and cauda equina treated by laminectomy at Cook County Hospital between 1969 and 1987 were reviewed. Sixty-one patients were operated upon within 72 hours of injury, 29 of whom (47.5%) experienced neurological improvement or pain relief. Twenty-seven patients were operated upon at a later time for associated injuries, 13 of whom (48.1%) experienced neurological improvement or pain relief. When laminectomy was delayed for more than 2 weeks, either arachnoid adhesions (15%) or occult abscesses (17%) were observed. From this review as well as from the literature, it appears that the timing of laminectomy for gunshot injuries of the thoracolumbar and lumbosacral spine is not essential to neurological recovery. It appears, however, that adequate debridement of these injuries, performed as soon as the patient is stable from any associated injuries, may help to mitigate the late sequelae of arachnoiditis, infection, and pain syndromes in the lower extremities. PMID- 2927614 TI - Endocrine function in patients with large pituitary tumors treated with operative decompression and radiation therapy. AB - Large pituitary tumors are still a common problem. Thirty consecutive patients underwent operative decompression and radiation therapy for large sellar and suprasellar tumors. They were studied prospectively in terms of their endocrine outcome. Ten of the patients had panhypopituitarism both before and after treatment. The other 20 patients had partial hormonal deficits prior to treatment. Ten (50%) of the 20 patients who had partial preoperative deficits went on to develop delayed onset of worsening in their endocrine function; 9 of the 10 developed panhypopituitarism, and 1 patient developed decreased thyroid function. The mean time from surgery until the onset of delayed worsening in endocrine function was 26.1 months. The mean age of those patients who developed delayed onset of worsening in pituitary function was significantly higher than that of those who did not develop further hormonal loss (40.5 +/- 3.1 years versus 52.0 +/- 4.1 years, P less than 0.05). None of the 10 patients with delayed onset of worsening in pituitary function had anatomical evidence by computed tomographic scan of tumor recurrence. Delayed onset radiation effect is the most likely cause of the late onset of worsening in endocrine function. PMID- 2927615 TI - Normal perfusion pressure breakthrough complicating surgery for the vein of Galen malformation: report of three cases. AB - Three cases are described of infants who developed malignant brain swelling (and in one case hemorrhage) after surgery for vein of Galen malformations. The cause for the brain swelling was felt to be due to hyperperfusion, or the "normal perfusion pressure breakthrough" syndrome. Although well-described for cerebral parenchymal arteriovenous malformations, cases of this complication occurring in vein of Galen malformations have not previously been reported. It is concluded from these cases that infants with large arteriovenous shunts, as attested by cardiac failure and cerebral atrophy, have an increased risk of developing this complication. PMID- 2927616 TI - Traumatic extradural hematoma of the cervical spine. AB - An example of a traumatic extradural hematoma of the cervical spine that occurred in a 32-year-old man who suffered from chronic ankylosing spondylitis is reported. Progressive sensory and motor deficit ensued some 3 hours after the patient fell from a standing position. The patient landed on his back, striking his head on the floor. After being helped up, he was able to walk unassisted to a nearby chair, where he sat down until his left lower extremity--and shortly afterwards, the right one--became numb and weak. On admission, the patient was found to have tetraparesis that was more pronounced in the lower extremities and associated with incomplete sensation to pinprick at level T7-T10. He also had painless distention of the urinary bladder. After a few hours, the weakness in his limbs increased and his sensory level rose to C5 bilaterally. A horizontal diastatic fracture across the vertebral body of C7 was discovered on plain x-ray films of the spine, and an extradural hematoma extending dorsally from C5 to T1 was revealed by emergency magnetic resonance imaging. After an emergency decompressive cervical laminectomy and removal of the clot, the patient rapidly regained complete neurological function, except with regard to both the urinary bladder and the rectum, which remained abnormal for almost 7 weeks after the operation. PMID- 2927617 TI - Intraspinal extension of an air cyst of the lung: case report. AB - We report the diagnostic evaluation and treatment of a cystic paraspinal and epidural lesion originally thought to be a neurofibroma or an arachnoid cyst. Intraoperatively, the lesion was found to be an air cyst of the lung that was successfully ligated. PMID- 2927618 TI - Growth of prolactinoma despite lowering of serum prolactin by bromocriptine. AB - Four patients with macroprolactinomas treated with bromocriptine had tumor growth and visual loss despite marked reduction in their serum prolactin levels. Explanations for this dissociation of tumor growth and prolactin measurement might include noncompliance. Patients treated with bromocriptine require periodic examination by computed tomographic scan or magnetic resonance imaging and neuro ophthalmological evaluation in addition to monitoring of serum prolactin. PMID- 2927619 TI - Atypical monoclonal plasma cell hyperplasia of the central nervous system: precursor of plasmacytoma with evolutionary considerations. AB - Hematopoietic proliferations rich in plasma cells rarely occur within the central nervous system without the involvement of other organ systems. Depending on their histological pattern and cellular composition, several different terms, including plasmacytoma, plasma cell granuloma, hyalinizing plasmacytic granulomatosis, and inflammatory meningioma, are used for these lesions. We report a left temporal dural lesion composed of plasma cells, lymphocytes, histiocytes, and rare eosinophils with hyaline changes and a suggestion of follicle formation, which stained predominantly for IgG and kappa light chains. This lesion arose in an otherwise healthy 52-year-old woman. Free kappa light chains without a monoclonal peak were found in the urine. We are aware of only two other heterogeneous, predominantly plasmacytic, solitary dural lesions that were found to be monoclonal on immunohistochemical examination. The label atypical monoclonal plasma cell hyperplasia appears to suit the morphological characteristics of our lesion. We suggest that a spectrum of solitary plasmacytic lesions may occur within the central nervous system and that atypical plasma cell hyperplasias have the potential to evolve into plasmacytoma. The preneoplastic nature of this lesion and its potential for evolution to malignant myeloma should be considered when planning treatment and lifelong follow-up for patients. PMID- 2927620 TI - Electrophysiological aid in high thoracic sympathectomy for palmar hyperhidrosis. AB - High upper thoracic sympathectomy using microsurgical techniques aided by electrical stimulation of the sympathetic chain is described. Use of the microscope facilitates identification and dissection of the sympathetic chain and minimizes the risk of pleural damage. Electrical stimulation of the sympathetic chain establishes the correct functional level for surgical excision. At the correct level, the threshold for piloerection, sudomotor response, and decrease in blood flow of the ipsilateral hand to electrical stimulation was minimal, and a six-fold increase in stimulus current causing current spread was required to dilate the ipsilateral pupil. After identification of the proper level, surgical excision can be done without risking postoperative Horner's syndrome. Excision of the appropriate ganglia and intervening sympathetic chain with placement of surgical clips on the proximal and distal nerve stumps provides tissue for histological analysis, decreases the opportunity for regeneration, and facilitates localization on postoperative x-rays. PMID- 2927621 TI - Oregon Head and Spinal Cord Injury Prevention Program and evaluation. AB - Head and spinal cord injuries are the leading causes of death and disability in the age group from 15 to 24. The Oregon Head and Spinal Cord Injury Prevention Program study sought to determine whether an educational assembly program would affect students' knowledge, attitude, and behavior. An observation study on shoulder belt use showed no increase in usage following the program. Seven Portland high schools (4 experimental, 3 control) participated in a questionnaire evaluation. Two weeks before and after the educational assemblies, 1,331 student surveys were distributed nonrandomly in classrooms. Presurveys were matched to postsurveys by student name, resulting in 626 matches. Survey items are grouped into three categories: knowledge, attitude, and behavior. The experimental schools demonstrated a statistically significant increase in knowledge (two tailed t test, p less than 0.01), suggesting that knowledge had been imparted. No change was found in attitude or behavior. To produce changes in attitude and behavior a reinforcement program might be necessary. Evaluation of the impact of the program on incidence may be premature. PMID- 2927622 TI - Abducted shoulder for cervical radicular pain. PMID- 2927623 TI - Photodynamic therapy of brain tumors. PMID- 2927624 TI - Diltiazem for aneurysmal subarachnoid hemorrhage. PMID- 2927625 TI - The performance on learning tasks of patients in the early stages of Parkinson's disease. AB - It is known that in animals learning is disrupted by caudate lesions; but there has been no agreement about whether pathology in the basal ganglia causes a similar impairment in man. Nineteen patients in the early stages of Parkinson's disease were tested on two associative learning tasks and on the Wisconsin Card Sorting Task; and their performance was compared with that of patients with frontal or temporal lobe lesions. On the two associative learning tasks there was no overall difference between the Parkinsonian group and the controls. However, a minority of the Parkinsonian patients performed very poorly on these tasks; and it was noted that these tended to be the older patients. PMID- 2927626 TI - Anomalies in the laterality of omissions in unilateral left visual neglect: implications for an attentional theory of neglect. AB - Patients suffering from unilateral left visual neglect may show problems in deploying attention generally in space, particularly in "controlled processing" type tasks (Schneider and Shiffrin), in addition to showing specifically lateralized attentional difficulties. The prediction is made that cueing to the left should result in a significant increase in right-sided omissions because of this general attentional difficulty. This hypothesis was confirmed, and two patterns of results were observed. One group continued to neglect a left stimulus in the cued condition, in spite of accurately reading a word on the left side, while the other group showed a mainly right-sided omission pattern. PMID- 2927627 TI - Cognitive mapping after unilateral temporal lobectomy. AB - An investigation of the extension of O'KEEFE and NADEL's [The Hippocampus as a Cognitive Map. Oxford University Press, Oxford 1978] theory of hippocampal functioning is described in patients who have undergone unilateral temporal lobectomy for the relief of epilepsy. A new spatial task, incorporating a recall for-designs test but based on studies of spatial memory and cognitive mapping in animals was devised. Results supported the prediction of temporal lobe structure involvement in the mediation of non-egocentric but not egocentric space, and of the role of right temporal lobe structures in conditions designed to encourage "place" but not "cue" learning strategies. The role of verbal mediation in task performance is also discussed. PMID- 2927628 TI - Prosopagnosia and object agnosia without covert recognition. AB - Investigations of the visual recognition abilities of the patient M.S. are reported. M.S. is unable to achieve overt recognition of any familiar faces, and many everyday objects. In Task 1 he showed semantic priming from name primes but not from face primes in a name recognition task. In Task 2 he showed no advantage in learning true (face + correct name) rather than untrue (face + someone else's name) pairings of faces and names. In Task 3 semantic priming of lexical decision was only found for object picture primes that M.S. was able to recognize overtly. In Task 4 faster matching of photographs of familiar than unfamiliar objects was only found for objects that M.S. was able to recognize overtly. These findings demonstrate an absence of covert recognition effects for M.S., consistent with the view that his impairment is primarily "perceptual" in nature. PMID- 2927629 TI - Category-specificity and modality-specificity in semantic memory. AB - Studies of agnosia have revealed two apparently orthogonal dimensions along which knowledge may break down. In some cases, knowledge of specific categories (such as living things) seems lost, regardless of the modality being tested. In other cases, knowledge in specific modalities (such as vision) seems lost, regardless of the category of stimuli being tested. These different sets of phenomena suggest different organizations for knowledge in the brain, the first by category and the second by modality. Unfortunately, possible confoundings between category, modality, and difficulty level in the previous studies prevent us from drawing strong conclusions from these data. The present study was aimed at assessing the nature of the breakdown in the semantic memory of a prosopagnosic patient, by orthogonally varying category and modality, while assessing difficulty level. The findings do not implicate a simple categorical or modality dependent organization of his knowledge, but rather an organization in which both category and modality play a role. PMID- 2927630 TI - Spatial distribution of the inhibitory effect of peripheral non-informative cues on simple reaction time to non-fixated visual targets. AB - It is known that reaction time (RT) for the detection of a light target at extrafoveal locations is lengthened by a previous non-informative light cue at the same location. We describe an additional inhibitory effect from cues remote from the target but occurring within the same lateral or altitudinal visual hemifield. Subjects made a speeded key-press response to the second of two successive light flashes in a pair while maintaining fixation. Each of the two flashes could appear at random in one of four positions, two in the right and two in the left visual fields, or two in the upper and two in the lower visual fields. We found an RT prolongation not only for cued over uncued positions, but also for within-field non-coincident cue-target pairs over between-fields cue target pairs. The within-field inhibitory effect, though smaller than the same location effect, was fully apparent even when the target occurred at 1 degree of visual angle from the midline and at 29 degrees from the cue. Both effects were seen with cue-target asynchronies ranging from 0.2 to 1.5 sec. The results are relevant to the understanding of the neural mechanisms for covert shifts of attention across the main meridians of the visual field. PMID- 2927631 TI - Left and right-handed dyslexic boys: an empirical test of some assumptions of the Geschwind-Behan hypothesis. AB - Twenty-six dyslexic boys (13 left-handers and 13 right-handers) were tested for hemispheric asymmetry with dichotic listening (DL) and a visual half-field test (VHF). The purpose of the study was an empirical test of the Geschwind-Behan [Proc. natn. Acad. Sci. USA 79, 5097-5100, 1982] hypothesis of a difference in hemispheric asymmetry between left- and right-handed dyslexic boys. Following Geschwind and Behan, left-handedness and dyslexia are caused by a common factor affecting the development of the left hemisphere in utero which results in a right hemisphere dominance. As a consequence, handedness but not language is shifted to the right hemisphere. We therefore predicted that left-handed dyslexics should be superior to right-handed dyslexics on visuospatial tasks, but perform similar to right-handers on verbal tasks. The results revealed a significant right ear advantage (REA) in both groups during a dichotic listening test to verbal stimuli. The left-handed group was however superior to the right handed group in recognition of visuo-spatial stimuli presented in the left half field in a visual half-field test. It is concluded that the results provide some, although weak, support for the Geschwind-Behan hypothesis. PMID- 2927632 TI - Changes in perceptual asymmetry with the menstrual cycle. AB - Changes in perceptual asymmetry between the premenstrual and postmenstrual phases of the menstrual cycle were assessed in 39 women. Perceptual asymmetry was measured with fused, single response dichotic listening tests. The usual right ear advantage (REA) for auditory language-related stimuli was significantly greater in the postmenstrual phase of the cycle. Subjects with repressive personality styles were less likely to show a change in REA with the cycle. These neuropsychological findings are related to previously described physiological and psychological features of the menstrual cycle and the repressive personality style. PMID- 2927633 TI - Hemispheric specialization for speech and non-verbal stimuli in Chinese and French Canadian subjects. AB - Dichotic speech (CV syllables) and non-verbal stimuli (melodies, tones and triple tones) were presented to 20 French Canadian (10 men, 10 women) and 19 Chinese (10 men, 9 women) right-handed university students to investigate cultural and sexual differences in auditory functional asymmetry. Analyses of variances on correct scores showed a REA in the perception of speech and a LEA in the perception of melodies and triple tones for both groups. Cross-cultural effects were observed for speech only, indicating a better overall performance on the part of French Canadian students. Moreover, women were better than men in the perception of tones and triple tones, suggesting that women may attend more to intonational information. Finally, the results for both ethnic groups showed the same pattern of interhemispheric functional asymmetry for speech and non-speech material. PMID- 2927634 TI - Cerebral lateralization of music perception in the dual task paradigm: unfamiliar melody recognition in sinistrals. AB - A dual task study of unfamiliar music perception during concurrent right and left hand finger tapping was conducted with a group of left-handed non-musicians. A pattern of symmetrical, bilateral suppression of finger tapping was observed during a concurrent music task of unfamiliar melody recognition. There was no evidence of trade-off effects in the dual task inasmuch as no interference in melody recognition was observed. The absence of attentional shifts strongly suggests that the bilateral symmetry in motor performance in the dual task condition reflects bilateralized cerebral organization among sinistrals for processing unfamiliar music. PMID- 2927635 TI - A directional bias for studies of laterality. AB - We have shown that a directional bias (D), previously thought to be unrelated to cerebral lateralization, is, in fact, intimately associated with it. In a group of fully consistent dextrals without familial sinistrality, the direction of lateral asymmetries depended upon the direction of D. Left-directed dextrals manifested the usual visual field advantages for linguistic and spatial material, while right-directed dextrals did not. D is therefore recommended as moderator variable for future studies of laterality. PMID- 2927636 TI - Impaired grating discrimination following right hemisphere damage. AB - We investigated the effect of unilateral brain lesions on visual discrimination of low-, middle- and high-frequency gratings. The performance of patients with right hemisphere lesions was significantly impaired compared with that of both controls and patients with left hemisphere lesions. This impairment was largely limited to patients with right posterior hemispheric lesions and was present with all spatial frequencies. These findings run counter to the hypothesis that high and low spatial frequencies are preferentially processed by different hemispheres. PMID- 2927637 TI - Ataxic hindbrain thinking: the clumsy cerebellum syndrome. PMID- 2927638 TI - Multiple sclerosis-like illness occurring with human immunodeficiency virus infection. AB - We describe seven men with a neurologic disease clinically indistinguishable from multiple sclerosis occurring in association with seropositivity for the human immunodeficiency virus, type 1 (HIV-1). Histopathology of the CNS obtained in three patients (2 by brain biopsy, 1 at autopsy) was consistent with MS. The neurologic symptoms preceded the onset of clinically evident immunosuppression in all patients. In three men, HIV-1 seropositivity was demonstrated concomitantly or within 3 months of the onset of their neurologic disease. In the others, features of MS preceded the demonstration of HIV-1 seropositivity by 41 months, 59 months, 11 years, and 18 years, respectively. Despite the superimposition of varying degrees of cellular immunodeficiency associated with HIV-1 infection, six of these men continued to experience relapsing neurologic symptoms. PMID- 2927639 TI - Lisuride, a dopamine agonist in the treatment of early Parkinson's disease. AB - A randomized, prospective trial in 90 de novo parkinsonian patients showed that 4 years' treatment with lisuride resulted in significantly fewer end-of-dose disturbances and peak-dose dyskinesias, but also less improvement in parkinsonian disability, than with levodopa. Early combination of lisuride and a low dose of levodopa, during a 4-year follow-up, resulted in a therapeutic response equal to that achieved with high-dose levodopa alone, but significantly fewer end-of-dose failures and dyskinesias. Thus it seems advisable that treatment should begin in the early phase of the disease with a dopamine agonist such as lisuride combined with a low dose of levodopa. PMID- 2927640 TI - Weekly alcohol consumption, cigarette smoking, and the risk of ischemic stroke: results of a case-control study at three urban medical centers in Chicago, Illinois. AB - To assess the role of current weekly alcohol consumption as a risk factor for cerebral infarction, we administered a pretested questionnaire to 205 middle-aged and elderly acute ischemic stroke patients and 410 outpatient controls matched by age, sex, race, and method of hospital payment. The frequency of hypertension (p less than 0.001) and transient ischemic attacks (p = 0.051), and mean weekly alcohol consumption (p = 0.0286) and mean pack-years cigarette exposure (p = 0.0168) were higher among stroke index cases than controls. For weekly alcohol consumption and mean pack-years cigarette exposure, there was a highly significant dose-response effect. In analyses to assess the possibility of mutual confounding effects of independent variables, we found hypertension and smoking to be independent risk factors for ischemic stroke, while alcohol consumption was not. Separate analyses by sex yielded similar results. We conclude that current weekly alcohol consumption may not be an independent risk factor for cerebral infarction in middle-aged and elderly patients. PMID- 2927642 TI - Neurobehavioral changes associated with caudate lesions. AB - We report behavioral and cognitive characteristics of 12 patients with caudate nuclei lesions, 11 unilateral and one bilateral. These patients developed an acute behavioral change characterized by apathy, disinhibition, or a major affective disturbance. The pattern of personality change correlated with size and location of lesion within the caudate but not the laterality. Seven patients were further compared with matched controls on a series of neuropsychological tests. Their performance was impaired on tasks requiring planning and sequencing. They had short attention spans and decreased free recall of episodic and semantic items with good recognition memory scores. Similar behavioral and cognitive changes also occur in early Huntington's disease, frontal-lesioned patients, and caudate-lesioned animals, and correspond to disturbances of specific frontal caudate circuits. These results implicate the caudate nuclei in mediating prefrontal behaviors and possibly in the conceptual integration of memories. PMID- 2927641 TI - Cerebral hyperemia, stroke, and transfusion in sickle cell disease. AB - To investigate cerebral hemodynamics in sickle cell disease (SCD), we used the 133Xenon inhalation technique of quantifying cerebral blood flow (CBF) in 67 patients. Clinical examinations and cerebral magnetic resonance imaging also were performed in all patients. Compared with age-matched healthy controls, CBF was elevated by 68% in patients, and inversely related to hematocrit. An experimental index of cerebral blood volume, pr4, was also elevated in the patients in a similar manner. Cerebral blood volume was positively correlated to CBF in SCD patients but not in controls. History of stroke and current neurologic symptoms were associated with lower flow and higher cerebral blood volume. Transfusion therapy reduced the hyperemia, the reduction being greater than expected by hematocrit elevation alone. These findings document a vasodilatory hyperemia in SCD. This dilatation may be a risk factor for ischemic distal-field infarctions, as visualized by MRI, due to a limitation of cerebrovascular reserve capacity. PMID- 2927643 TI - Synaptic loss in Alzheimer's disease and other dementias. AB - The extent and location of neuronal losses necessary or sufficient to produce dementia in patients with Alzheimer's Disease (AD) is unknown. To approach this question, we studied synaptic terminals in postmortem brain tissue utilizing immunohistochemical techniques. We used antibodies against two proteins found in synaptic terminals--synapsin I and synaptophysin--as synaptic markers in the hippocampal complexes of eight patients with autopsy-proven AD and eight nondemented control subjects. Quantitative microscopy measured the regional density of synaptic staining. All AD patients showed a striking decrease in synaptic staining in the outer half of the molecular layer of the dentate gyrus compared with control brains, where the density of synaptic terminals was uniform throughout. In an additional patient with progressive degenerative dementia but without plaques or tangles on neuropathologic examination, similar depletion of synaptic staining was seen in the dentate gyrus. Quantitative densitometric analyses confirmed the focal decrease in synaptic staining in the outer half of the molecular layer in demented patients. We also found a slight increase in synaptic staining in the inner half of this layer. PMID- 2927644 TI - The spectrum of imaging and neuropsychological findings in Pick's disease. AB - To seek improved methods for the diagnosis of Pick's disease, we reviewed imaging studies of four women and two men (ages 48 to 65 years at onset) and psychometric testing of three of them with autopsy or biopsy-proved Pick's. The presence of Pick bodies was required for the diagnosis. Seven patients with biopsy-proved Alzheimer's disease served as a comparison group. In the Pick's patients, CT in five of six showed marked frontal pole or temporal pole atrophy, which clearly differed from the pattern of cerebral atrophy seen in the Alzheimer's patients. Psychometric testing showed performance patterns that tended to differ from those of the Alzheimer's patients in that recent memory was relatively preserved despite marked impairment of executive functions. The distinctive psychometric pattern in the Pick's patients was evanescent, however. Thus, there were imaging and psychometric findings of potential diagnostic value for Pick's disease, but, for different reasons, they were imperfect. PMID- 2927645 TI - Immune-reactive cells in multiple sclerosis mucosal secretions. AB - External secretions from multiple sclerosis (MS) patients show immunoglobulin abnormalities consistent with mucosal inflammation. In this study we collected tears and parotid saliva from ten normal subjects and ten MS patients to examine for free-floating inflammatory cells. We found lymphocytes, macrophages, and plasma cells at low numbers in normal secretions, but at much higher numbers in MS secretions. Using an immunobead rosette technique, most of the lymphocytes were null cells. However, we found increased T lymphocytes in the secretions of clinically active MS patients. The extensive mucosal surfaces of the MS patient could provide a peripheral source for activated lymphocytes that subsequently enter brain. PMID- 2927646 TI - Familial idiopathic striopallidodentate calcifications. AB - We report a father and son with striopallidodentate calcifications. Metabolic studies excluded calcium/phosphorus metabolism disturbances and no specific etiology was found. The structure of the calcified areas differed, on magnetic resonance imaging, depending on location and, probably, age. There are nine families with similar clinical and radiologic backgrounds and no evident etiology in the literature. Transmission is most often autosomal dominant, and in contrast with physiologic senescent basal ganglia calcification, the prognosis appears to be poor. PMID- 2927647 TI - Ptosis and supranuclear downgaze paralysis. AB - A patient developed the unusual combination of a supranuclear downward gaze paralysis and bilateral ptosis. It was caused by a single midbrain glioma. Other ocular motor functions were intact. The neuropathologic examination showed a tumor growing mainly around the third ventricle and the aqueduct. The findings agree with recent experimental evidence that a network of neural elements involved in eyelid control lies in the supraoculomotor area immediately dorsal to the oculomotor nucleus. PMID- 2927648 TI - Reflex epilepsy and nonketotic hyperglycemia in the elderly: a specific neuroendocrine syndrome. AB - We present five elderly patients with focal reflex or posture-induced seizures and nonketotic hyperglycemia (NKH). Each patient exhibited interictal focal findings, such as hemiparesis or hemisensory or aphasic deficits. With control of the hyperglycemia, the seizures stopped, and the neurologic deficits resolved. The syndrome of focal reflex epilepsy and neurologic deficits in the elderly is transient and almost invariably related to NKH, thus representing a specific neuroendocrine syndrome. PMID- 2927649 TI - Episodic confusion and tremor associated with extrahepatic portacaval shunting in cirrhotic liver disease. AB - In an elderly male patient with alcohol-related liver disease, who developed episodic confusion and tremor, we found a large extrahepatic portacaval shunt. He had no clinical or laboratory evidence of liver dysfunction except for an elevated serum ammonia level that increased further in response to an ammonium chloride challenge test. Extrahepatic portacaval shunting causing episodic confusion and tremor may occur with alcoholic liver disease without overt liver failure and may require abdominal angiography or a transhepatic portogram to demonstrate the shunt. PMID- 2927650 TI - The effect of bilateral visual cortex lesions on the development of eye movements and perception. AB - We studied the eye movements and visual perception in a man with extensive bilateral occipital lesions acquired at birth. He had 3/500 acuity, limited visual fields, and extrafoveal fixation attributable to an intact left superior visual cortex. Analysis of digitized electro-oculography and magnetic search coil data showed normal saccade dynamics. He could make voluntary saccades. Smooth pursuit of suprathreshold targets was mostly saccadic and did not improve with added nonvisual cues. Our results support the hypothesis that the visual cortex is crucial to the development of eye movements. The foveal representation in the occipital lobes, missing in this subject, is needed for development of normal smooth pursuit. PMID- 2927651 TI - Unilateral pursuit-induced congenital nystagmus. AB - We describe two patients with a lifelong history of oscillopsia only when following objects moving toward their left side. Neurologic examination was normal except for eye movements. The patients showed nystagmus during any tasks that required visual following toward the left (ie, smooth pursuit, optokinetic nystagmus, and vestibulo-ocular-reflex-suppression), but had no nystagmus during fixation of stationary targets or visual following tasks to the right. Eye movement recordings showed waveforms during pursuit to the left that were typical of congenital nystagmus. PMID- 2927652 TI - Transcranial magnetic stimulation: an assessment of cognitive and other cerebral effects. AB - To assess possible persistent cerebral effects, we acquired EEG, measured serum prolactin, and administered cognitive and motor tests before and after transcranial magnetic stimulation of 30 healthy adults. We found no detrimental effects on EEG or test performance. A slight but statistically significant decline in serum prolactin lacked correlation with the extent of stimulation. PMID- 2927653 TI - Criteria for establishing the validity of genetic recombination in myotonic dystrophy. PMID- 2927654 TI - High-dose intravenous human immunoglobulin in chronic inflammatory demyelinating polyneuropathy. AB - We treated nine consecutive patients with chronic inflammatory demyelinating polyneuropathy (CIDP) with high-dose intravenous human immunoglobulin (HIG), and clinical recovery rapidly followed. Disability that had persisted for months or years was often reversed in days. There were no major adverse reactions to HIG infusions. PMID- 2927655 TI - Seizures in hospitalized cocaine users. AB - We reviewed the records of 283 cocaine abusers consecutively admitted to a municipal hospital, and identified eight patients (2.8%) who presented with seizures. Four (1.4%) had focal or generalized seizures temporally associated with cocaine use. Based on these four cases and five previous reports, we conclude that although seizures are relatively rare in hospitalized cocaine users, they are provoked by all major routes of administration, and may be partial or generalized. PMID- 2927656 TI - Thalamomesencephalic strokes after cocaine abuse. AB - Three young patients developed strokes of rostral midbrain and thalamus shortly following cocaine abuse. Two had infarctions and one had a hemorrhage, but none had clear risk factors other than cocaine for this relatively uncommon type of stroke. Toxicologic analysis confirmed isolated cocaine use in each patient. In the two cases of infarction studied angiographically, one had normal findings and the other had focal narrowing of the P1 segments of the posterior cerebral arteries bilaterally. Since the P1 segment has a uniquely sparse perivascular sympathetic supply, we suggest that direct adrenergic-mediated vasoconstriction is not critical to the production of cocaine-associated stroke. PMID- 2927658 TI - The EEG response to diffuse and patterned photic stimulation during acute untreated alcohol withdrawal. AB - We studied the responses to diffuse and patterned stroboscopic light stimulation prospectively in 49 individuals during acute alcohol withdrawal prior to pharmacologic treatment. Photomyogenic responses (PMR) occurred in only two (4%) of those tested, and photoparoxysmal responses (PPR) never occurred. These findings suggest that PMR occur far less often during alcohol withdrawal than previously thought and that PPR may not be a direct manifestation of alcohol withdrawal. PMID- 2927657 TI - Cerebellar atrophy following acute intoxication with phenytoin. AB - A patient developed marked cerebellar atrophy after a single suicidal intoxication with 7 grams phenytoin. The clinical signs of cerebellar dysfunction subsided very slowly and incompletely within 18 months. We documented the cerebellar atrophy by CTs 4 weeks and 1 year after the intoxication, and we suggest that a single severe acute intoxication with phenytoin may directly cause cerebellar degeneration. PMID- 2927659 TI - Dose-dependent memory impairment in Parkinson's disease. AB - Variation in plasma dopamine level between the time of original learning and subsequent memory retrieval causes a state-dependent memory impairment in Parkinson's disease. The occurrence of this phenomenon is not related to either progression of disease or duration of therapy, but is more likely to occur with high-dosage levels of levodopa-carbidopa. PMID- 2927660 TI - Magnetic resonance imaging in pathologically proven Hallervorden-Spatz disease. AB - We present an 11-year-old girl in whom high field strength MRI performed 2 1/2 years and 6 months before her death showed prominent hypointensity in the globus pallidus and substantia nigra consistent with iron deposition. This finding suggested Hallervorden-Spatz disease, which was confirmed at autopsy. PMID- 2927661 TI - Distribution of a putative endogenous modulator of the GABAergic system in human brain. AB - Diazepam binding inhibitor (DBI) is a novel neuropeptide purified from rat, cow, and human brain that allosterically modulates GABAergic transmission by binding to benzodiazepine (BDZ)-recognition sites. Using a specific radioimmunoassay for human DBI, we investigated the distribution of this peptide in different brain areas. We characterized with high-pressure liquid chromatography the DBI immunoreactivity in brain tissue obtained by biopsy and autopsy; we detected one molecular species of DBI in both instances. The regional distribution of DBI in the human brain is similar to that observed in rat brain: high concentrations in cortical and limbic areas, cerebellum, and brainstem, and low concentrations in the basal ganglia. These data suggest a modulatory role for DBI in human brain. PMID- 2927662 TI - Unilateral "akathisia" in a patient with AIDS and a toxoplasmosis subthalamic abscess. PMID- 2927663 TI - Acute ischemic brachial plexus neuropathy following radiation therapy. PMID- 2927664 TI - Decreased viability of skin fibroblasts from patients with glutamate dehydrogenase deficiency. PMID- 2927665 TI - Isolated midbrain lesion resulting from closed head injury: a unique presentation of ataxic hemiparesis. PMID- 2927666 TI - Orofacial impairment in Parkinson's. PMID- 2927668 TI - Task-specific dystonias. PMID- 2927667 TI - Sternocleidomastoid and trapezius dissociation. PMID- 2927669 TI - Ictus emeticus. PMID- 2927670 TI - Hemispatial neglect. PMID- 2927671 TI - Molecular and clinical correlations of deletions leading to Duchenne and Becker muscular dystrophies. AB - Human DMD cDNA probes have been used to delineate possible deletions in 160 affected males. Approximately 56% of these individuals had detectable deletions, 29% of which mapped to a region centered around 500 kb from the 5' end of the gene whereas 69% mapped to a region located centrally 1,200 kb from the 5' end. We have observed no correlation between the extent of a deletion, its location, and clinical severity of the associated disease. For some cases with deletions in the two high-frequency deletion regions, the predicted effect upon translational reading frame of the resultant dystrophin mRNA did not correlate with the associated disease phenotype. PMID- 2927672 TI - Duchenne muscular dystrophy: patterns of clinical progression and effects of supportive therapy. AB - Two-hundred eighty-three boys with Duchenne dystrophy and 10 with Becker dystrophy have been followed for up to 10 years in a protocol that accurately measured their function, strength, contractures, and back curvature. Clinical heterogeneity is noted. Patients whose muscles were stronger were more likely to die from a cardiomyopathy. Weaker patients died from respiratory failure. A series of milestones is defined, which is of use in following the illness in an individual patient. This approach permits a scoring system that allows the severity of the disease to be defined in an individual boy. Evaluation of physical therapy and surgical intervention shows that night splints and scoliosis surgery are effective forms of treatment. PMID- 2927673 TI - Neurobrucellosis: clinical characteristics, diagnosis, and outcome. AB - We report 13 patients with neurobrucellosis categorized into five groups: acute meningoencephalitis; papilledema and increased intracranial pressure, meningovascular, CNS demyelinization, and peripheral neuropathy. We treated the patients successfully, without relapse, with two or more antimicrobials: rifampicin, co-trimoxazole, and doxycycline. PMID- 2927674 TI - Infarcts in the territory of the deep perforators from the carotid system. AB - We studied risk factors and presumed causes of infarct in 100 consecutive patients with a first stroke, who had an appropriate CT-proven infarct in the territory of the deep perforators from the carotid system (ITDPCS). The infarct involved the territory of the lenticulostriate arteries in 65 cases, the anterior choroidal artery in 23 cases, watershed zones between these two territories in four cases, and another territory in eight cases. In 42% of the patients, we felt the cause of the infarct to be small-artery disease. In 36%, at least one source of embolism was present (in 27% from the internal carotid artery, in 17% from the heart), either with (25%) or without (10%) associated hypertension (HT) and diabetes mellitus (DM). Other possible less common etiologies included migraine, syphilitic angiitis, and systemic diseases. We have confirmed that HT or DM are the most common etiologic factors of ITDPCS. However, large-artery disease and cardioembolism may be more important than previously assumed. PMID- 2927675 TI - Dissecting aneurysm of the vertebral artery and cervical manipulation: a case report with autopsy. AB - A 35-year-old woman with 3 weeks of cervical pain developed ischemia in the basilar artery territory following cervical manipulation. At autopsy, there was a dissecting aneurysm within the third segment of the right vertebral artery. The pathologic changes in the lower and the upper part of the dissecting aneurysm were different, indicating recurring bleeding. Cervical manipulation could have accounted for one recent dissection, but not for another, which was a few weeks old. This suggests that cervical pain, which prompted the manipulation, may have been the first symptom of the dissection, and manipulation of the neck precipitated the stroke by inducing bleeding within the dissecting aneurysm. PMID- 2927676 TI - Intraluminal clot in the vertebrobasilar circulation: clinical and radiologic features. AB - We studied 15 patients with angiographically documented intraluminal clot in the vertebrobasilar (VB) circulation and ischemic stroke. Progressive brainstem signs were the most common presentation; the neurologic deficit was maximum at stroke onset in 4. Seven experienced their first symptoms during sedentary activities. Thirteen of the initial 15 CTs revealed infarcts in the VB territory, 7 with multiple foci. Intraluminal clot was present in the vertebral artery in 7 patients (2 bilateral), basilar artery in 7, posterior cerebral artery in 5, and superior cerebellar artery in 1. Multiple clots were seen in 5 patients. Stroke risk factors were present in the majority of cases. Although cardiac source embolism was the most common single etiology (4 patients), most patients had other causes including migraine, coagulopathy associated with malignancy and nephrotic syndrome in systemic lupus erythematosus, vertebral artery dissection with local embolism, delayed irradiation arteriopathy, and a fusiform, ectatic basilar artery. Six (40%) died within 5 months of follow-up. Intraluminal clot in the posterior circulation is a marker for multiple stroke mechanisms, not all of which are embolic. Intraluminal clot should prompt investigations into occult risk factors when no cause appears obvious. PMID- 2927677 TI - Electroencephalographic studies of simple partial seizures with subdural electrode recordings. AB - We used subdural electrodes to study the EEG features of simple partial seizures in 7 patients. We detected epileptiform discharges in 61 of 68 subdurally recorded simple partial seizures compared with 6 of 55 simple partial seizures recorded with scalp electrodes (p less than 0.0001). The onset of 36 nonmotor simple partial seizures was detected only by the medial and basal temporal subdural electrodes, and the onset of 25 simple partial seizures with motor manifestations was recorded by subdural electrodes only from the lateral cortex of the posterior frontal lobe. There was a close correspondence between the area first involved in the epileptiform discharge during simple partial seizures and the area first involved during complex partial and secondary generalized tonic clonic seizures. Subdural electrodes may be effective in localizing the onset and spread of simple partial seizures, including those that arise from the medial temporal lobe. PMID- 2927678 TI - Maturation of the vestibulo-ocular reflex in normal infants during the first 2 months of life. AB - We measured the dynamic properties of the vestibulo-ocular reflex (VOR) in 20 healthy, newborn babies, using sinusoidal and velocity-step rotational stimuli. With sinusoidal stimuli, quick phases of nystagmus were uncommon and there was a large phase lead of eye position over head position that exceeded 20 degrees at frequencies below 0.5 Hz. With velocity-step stimuli, primary nystagmus lasted for a mean duration of 10 seconds and was followed by an early reversal phase of nystagmus. By 2 months of age, primary nystagmus induced by velocity-step stimuli was more prolonged (mean duration, 15 seconds) and the reversal phase occurred later. We postulate that these changes reflect maturation of visual pathways essential in calibrating the VOR so that vision remains clear during head perturbations. PMID- 2927679 TI - Preliminary observations on brain energy metabolism in migraine studied by in vivo phosphorus 31 NMR spectroscopy. AB - We measured brain energy phosphate metabolism and intracellular pH (pHi) in a cross-sectional study of migraine patients by in vivo phosphorus 31 NMR spectroscopy. During a migraine attack the ratio ATP/total phosphate signal (mole % ATP) was preserved, but there was a decrease in mole % phosphocreatine (PCr) and an increase in mole % inorganic phosphate (Pi) resulting in a decrease of the PCr/Pi ratio, an index of brain phosphorylation potential. This was found in classic but not common migraine. Mole % Pi was also increased in combined brain regions between attacks. There was no alteration in brain pHi during or between attacks. Energy phosphate metabolism but not pHi appears disordered during a migraine attack. PMID- 2927680 TI - Cognitive impairments associated with early Parkinson's disease. AB - We administered a battery of cognitive tests to 41 recently diagnosed Parkinson patients and 41 controls to assess the early neuropsychological changes associated with Parkinson's disease (PD). Parkinson subjects did as well as controls on tasks assessing attention and select language and visuospatial measures. However, PD subjects did significantly worse on embedded figures, facial recognition, proverbs, and verbal and figural memory measures, and made more perseverative responses on a set shifting task. A discriminant function of measures of proverbs, embedded figures, and memory accounted for 22% of the variance between groups. These data suggest that the cognitive changes in early PD are more pervasive than originally described and may reflect the onset of a more widespread pathologic process. PMID- 2927681 TI - End-plate dysfunction in acute organophosphate intoxication. AB - Acute organophosphate intoxication resulting from suicide attempts in 14 patients produced a series of electrophysiologic abnormalities that correlated with the clinical course. Spontaneous repetitive firing of single evoked compound muscle action potentials (CMAP) was the earliest and most sensitive indicator of the acetylcholinesterase inhibition. A decrement of evoked CMAP following repetitive nerve stimulation was the most severe abnormality. At the height of the intoxication no CMAP was evoked after the first few stimuli. The decrement increment phenomenon occurred only at milder stages of intoxication and its features are characteristic of acetylcholinesterase inhibition. These electrophysiologic features proved to be the most useful for determining initial severity and clinical course of the acute organophosphate intoxication and differentiated this syndrome from those of myasthenia gravis, Eaton-Lambert syndrome, and botulism. PMID- 2927683 TI - Blink reflex excitability recovery curves in patients with spasmodic dysphonia. AB - We studied 12 patients with spasmodic dysphonia (SD) and 12 healthy control subjects. The patients, who had no symptomatic involvement of the eyes, were evaluated for increased excitability of blink reflexes, which is characteristic of blepharospasm and generalized dystonia. We measured symptom severity from sound spectrograms of five sentences, including sentence production time, number of pitch phonatory breaks, and percentage of aperiodic phonation. We evoked blink reflexes by electrical and mechanical stimulation, and assessed excitability by obtaining excitability recovery curves and responses to trains of stimuli. Patients and controls differed from each other in test R2 amplitude attenuation across all intervals from 150 to 1,000 msec to electrical and mechanical stimulation. Our results indicate that patients with SD have increased excitability of blink reflexes, which suggests that the dystonia involves not only the larynx but also other anatomical structures. PMID- 2927682 TI - Cortical blindness due to osmotic disruption of the blood-brain barrier by angiographic contrast material: CT and MRI studies. AB - Numerous experimental studies have demonstrated disruption of the blood-brain barrier by the hyperosmolar, iodinated contrast agents in common use for intravascular injection during radiologic studies. We report 4 cases in which cortical blindness occurred after cerebral angiography. The patients underwent x ray CT within 1 hour. CT showed abnormal contrast enhancement in the occipital regions in all 4 instances. Two patients underwent MRI; 1 of these manifested abnormal high-signal intensity in the occipital lobes on T2-weighted images. Only 2 previous cases documenting immediate contrast enhancement within the brain substance on CT following angiography are in the literature. PMID- 2927684 TI - Hemifacial spasm associated with epidermoid tumors of the cerebellopontine angle. AB - Hemifacial spasm (HFS) is rarely due to serious compressive lesions, such as tumors, aneurysms, or vascular malformations, located in the cerebellopontine angle. Because of the interesting association of HFS with epidermoid tumors, we reviewed the records of all patients with HFS and all patients with intracranial epidermoid tumors seen from January 1975 to December 1986. Of the 18 patients who had epidermoid tumors of the cerebellopontine angle, 3 (17%) had a facial movement disorder that resembled HFS at sometime during their illness. There were 429 patients who had HFS with no obvious serious compressive lesion of the facial nerve. Therefore, HFS was associated with epidermoid tumor in 0.7% of cases. All 3 patients developed other findings due to involvement of adjacent neural structures. Patients with HFS have a low probability of having a serious compressive lesion, but those with atypical features should be evaluated for cerebellopontine angle masses such as epidermoid tumors. PMID- 2927686 TI - Hysterical gait disorders: 60 cases. AB - Simulated gait abnormalities involve weakness of 1 or both legs or ataxia and trembling. The patterns rarely duplicate those of neurologic disability and are usually promptly suspected of being functional by the experienced clinician. As with other pseudoneurologic signs, normal underlying neurologic function must be demonstrated. A dramatic cure is the best diagnostic evidence, and a bias toward organic etiology is warranted by a relatively greater risk in delayed diagnosis. Dystonia and chorea are the signs most likely to be mistaken for functional conditions. While CT and MRI now provide a welcome diagnostic safety net, the variety of hysterical gaits, and probably the effectiveness of "moral" treatment, does not appear to have changed appreciably in the past century. PMID- 2927685 TI - Maximal and minimal motor nerve conduction velocities in amyotrophic lateral sclerosis. AB - In 15 patients with amyotrophic lateral sclerosis (ALS) and 20 age-matched control subjects, we measured the maximal and minimal motor nerve conduction velocities of the ulnar nerve as well as the action potential amplitude of the abductor digiti minimi muscle. Both maximal and minimal motor nerve conduction velocities in ALS patients were significantly lower than those in the control group. However, the difference between the maximal and minimal conduction velocities in each ALS patient was not statistically different from that in each control subject. The maximal action potential amplitude of the muscle in the ALS patients was significantly smaller than that in the control group. PMID- 2927687 TI - Time course of carbamazepine autoinduction. The VA Cooperative Study No.118 Group. AB - We sequentially determined carbamazepine clearance values in 17 patients at the end of weeks 1, 2, 4, 8, and 12 of monotherapy. There were no significant differences among these clearance values. In 11 of 17 patients, week 1 clearance accurately predicted week 12 carbamazepine serum concentration (within +/- 33%). Our data indicate that carbamazepine autoinduction was completed within the first 1 or 2 weeks of monotherapy. Serum concentration values obtained after 1 week of monotherapy, using our dosing regimen, can be used to predict directly the dosing rate needed to obtain a specific serum concentration in most patients. PMID- 2927688 TI - Mechanism of pain caused by the nerve-root tension test in patients with sciatica. AB - We describe 2 instances where sciatic nerve block prevented pain in the sciatic nerve distribution caused by the nerve-root tension test in patients with radiculopathy. We hypothesize that antidromic activation of nociceptors from the injured root is a mechanism underlying sciatica. PMID- 2927689 TI - Dysplastic gangliocytoma and intractable partial seizures in childhood. AB - We describe the clinical, radiologic, and EEG features of 3 children who had dysplastic gangliocytomas of the cerebral hemispheres and drug resistant partial seizures that began in infancy. Following cortical resection, 2 are seizure-free and the third almost seizure-free. The dysplastic gangliocytoma may be an important and surgically remediable cause of very early malignant partial seizures. PMID- 2927691 TI - Phenobarbital for status. PMID- 2927690 TI - Myotonic dystrophy is not associated with abnormalities of calcium homeostasis. PMID- 2927692 TI - Skeletal myorhythmia. PMID- 2927693 TI - Sensory levels with brainstem lesions. PMID- 2927694 TI - Parkinson's disease and dementia. PMID- 2927695 TI - Memory impairment in myasthenia gravis. PMID- 2927696 TI - MS in twins. PMID- 2927697 TI - One-stage colectomy and ileorectal anastomosis for complete left-sided obstruction of the colon. AB - Fourteen patients with complete left-sided obstruction of the colon were treated by a one-stage emergency colectomy and primary ileorectal anastomosis. One patient died from anastomotic leakage. In selected patients the method should be considered as an alternative to the staged procedure. PMID- 2927698 TI - Thumb reconstruction in the severely damaged hand using finger remnants. AB - In severely injured hands with loss of the thumb and irreparable damage to one or more fingers, the thumb can often be reconstructed by transfer of a comparatively useless finger remnant. Sometimes this reconstruction can be performed at the time of primary treatment, but generally this is done as a secondary procedure. Seven patients were treated and considerable functional improvement was obtained in all instances. PMID- 2927699 TI - Urological complications following aorto-iliac reconstructive surgery. AB - The incidence of urological complications after aorto-iliac graft surgery was prospectively studied in 49 patients and retrospectively in 35 other patients operated on more than five years before. Follow-up of all 49 patients was one year. In one patient a mild asymptomatic hydronephrosis was discovered after four months. Two patients developed urinary tract infections and two other patients a urethral stricture. Late hydronephrosis was encountered in one out of 35 patients. This patient had mild unilateral hydronephrosis. Based on the results of this study, routine examinations to detect hydronephrosis after aorto-iliac reconstructive surgery in patients with an uneventful course are not necessary. Intermittent postoperative catheterization of the bladder is advised to prevent urinary tract infections and/or urethral strictures. PMID- 2927700 TI - Surgical treatment of a bifid blind-ending ureter: report of two cases. AB - Two patients with a bifid blind-ending ureter are reported. Both patients were treated surgically with good results. The etiology, physiopathology and the treatment of choice for this rare urological anomaly are discussed. PMID- 2927701 TI - Aneurysm of the popliteal vein with multiple pulmonary thrombo-emboli: a case report. AB - Venous aneurysms are uncommon pathologic entities, which can lead to serious complications. A 75-year old patient is reported with a thrombosed aneurysm of the popliteal vein and multiple pulmonary thrombo-emboli. The diagnosis is in general based on venography. In the present case, however, ultrasonography was performed and led to the wrong diagnosis because of unfamiliarity with this entity. When ultrasonography of the popliteal fossa is performed, the possibility of aneurysms of the popliteal vein should be considered. PMID- 2927702 TI - Iatrogenic chylous ascites: operative or conservative approach. AB - Postoperative chylous ascites is a rare complication of aortic surgery. Two patients are presented with postoperative chylous ascites after abdominal aortic surgery. The value of either conservative management or an operative approach or peritoneo-venous shunting is discussed. PMID- 2927703 TI - Volvulus of the stomach after traumatic hernia diaphragmatica. AB - A patient with gastric volvulus after traumatic diaphragmatic rupture is reported. The trias of Borchardt (pain in epigastrio with gastric distension, hiccups with the inability to vomit, inability to secure the passage of a nasogastric tube) must raise the suspicion on acute gastric volvulus, especially if these abdominal complaints are associated with blunt abdominal trauma in the past. In these cases, lateral X-ray examinations of the chest and swallowing studies establish the diagnosis. PMID- 2927704 TI - [Cerebral ischemic malacia. A retrospective study of CAT scan-documented cases]. AB - One hundred male patients affected by ischaemic stroke were studied with the use of CT scans. A clinical-biohumoral pattern was traced for every patient, with particular regard to the incidence of risk factors for stroke of which systolic arterial hypertension, appear to be the most frequent. It would be useful to extend this research to female patients as well in order to discover any significant differences between sexes. PMID- 2927705 TI - [Is malignant mesothelioma of the pleura only an occupational disease?]. AB - Ten cases of pleural malignant mesothelioma identified histologically at the Department of General Medicine in May 1983-June 1987, are examined in this paper. Occupational risk factors and clinical features are discussed. Only one patient (10%) was subjected to occupational risk of asbestos exposure (as a smith) while the other nine patients showed a negative anamnesis for direct or indirect asbestos exposure. However, one of these patients was a tram-driver. The patients' mean age was 69 years old. 7 patients were males. 7 patients were born in an industrialized urban environment, 3 were born in an agricultural environment: all had been living in Milan for many years. Pleural fluid cytology was only useful in the diagnosis of 2 cases. This study suggests that pleural malignant mesothelioma is a neoplasm which also affects people not exposed to asbestos at work and that its frequency is increasing. The most probable cause is environmental contamination by asbestos of urban industrialized areas. Thus, it is necessary to eliminate this mineral from all manufacturing processes in which asbestos is not indispensable. PMID- 2927706 TI - [Hepatitis B vaccination with the plasma-derived Hevac-B Pasteur vaccine. A comparison of 2 populations: hospital personnel and hemodialysis patients]. AB - A vaccination experiment using plasma-derived Hevac-B anti-hepatitis vaccine was conducted on two groups at high risk of HBV infection: hospital staff and hemodialyzed subjects. The qualities of the vaccine and the most important directions on how to use it rare briefly presented with a report on the protocol and the results of the vaccine cycle in both groups. It is concluded that the Hevac-B vaccine is efficacious in healthy subjects at risk, but gives an unsatisfactory result in immune deficient subjects, like those under haemodialysis. PMID- 2927707 TI - [A graphic study of levers in the human body]. AB - A graphical method is proposed which permits one to determine by a simple drawing procedure for any lever in the human body the intensity of the muscular force and of the force acting on the fulcrum (i.e. on the joint) and the direction of this latter. The method is compared with the conventional one, in which muscular force is first determined by a calculation in which the geometrical lever arms are measured, and then fulcrum force is obtained by means of a vector construction. The new graphic method permits one to simultaneously obtain the intensity and the direction of the forces acting on the lever, without measuring or computing torque values. PMID- 2927708 TI - [The treatment of spontaneous pneumothorax. A report on 160 cases]. AB - The results achieved in the treatment of 160 cases of spontaneous pneumothorax in 1976-1986 are examined. Pleural aspiration drainage was practised in 141 cases and produced a permanent cure. 5 cases were surgically treated. Hospitalisation time was less than 16 days in 110 cases. PMID- 2927709 TI - [Anamnesis: a methodologic approach and diagnostic value]. PMID- 2927711 TI - Hypothalamic angiotensinergic fibre systems terminate in the neurohypophysis. AB - A new affinity-purified anti-angiotensin II/III antibody ('BODE') was used to determine the location of angiotensin-like immunoreactivity in the paraventriculo hypophysial pathway, especially in the pituitary. Angiotensin-like immunoreactivity was shown to be concentrated in the neurohypophysis and was characterised by a dense plexus of fibres and terminals. PMID- 2927710 TI - Intracellular dyes mask immunoreactivity of hippocampal interneurons. AB - The results of several studies have suggested that local circuit neurons, or interneurons, of area CA1 of hippocampus use gamma-aminobutyric acid (GABA) as their neurotransmitter. However, when these cells were labelled by intracellular dye injection, and examined immunocytochemically with antisera raised against GABA, none of the interneurons were immunoreactive. Numerous non-injected interneurons in the same tissue section were clearly immunoreactive. These results suggest that intracellular dyes interfere with immunocytochemical staining of hippocampal interneurons. PMID- 2927712 TI - An electrophysiologically defined trigemino-reticulo-facial pathway related to the blink reflex in the cat. AB - This study examines the direct projection of neurons in the pontomedullary reticular formation (RF) to the dorsal division of the facial nucleus (FN), where the orbicularis oculi motoneuron pool is located, and the nature of synaptic inputs to the RF neurons from the supraorbital branch of the trigeminal nerve (SON), using electrophysiological techniques in anesthetized cats. A large number of the RF neurons directly projected to the ipsilateral FN dorsal division, and some of these neurons issued axon branches probably terminating on motoneurons in the division. Many of the RF neurons projecting to the dorsal division were synaptically activated by ipsilateral SON stimulation. Most latencies of their activation were between the latencies of the early and late blink reflex responses, and the remaining latencies were shorter than those of the early response. These results suggest that the RF neurons mediate both the early and the late blink reflex responses, but mainly the late response, as premotor relay neurons. PMID- 2927713 TI - Expression of neurofilament immunoreactivity in developing rat cerebellum in vitro and in vivo. AB - The developmental expression of neurofilaments immunoreactivity was examined in frozen sections and in primary cultures of rat cerebellum by immunocytochemistry with a series of monoclonal antibodies and with a polyclonal antibody. In tissue sections immunocytochemical staining with all the antibodies used was observed in basket cells where adult-like appearance could be detected by 14 days of age and adult-level intensity was achieved by about 25 days. Granule cells remained unstained. Intense staining appeared in cerebellar white matter as early as 7 days after birth. In contrast, neurofilaments immunoreactivity was detected in cultured granule cells from 7-day-old cerebellum. Only polyclonal antibodies reacting with the highly conserved middle alpha-helical domain of the neurofilament subunits were reactive in culture. Staining could be detected in the nerve cell bodies from the first day after plating; thereafter staining intensity increased and was also distributed in neurite extensions. We conclude that unlike their counterparts in vivo cultured embryonic granule cells can express certain neurofilaments immunoreactivity. PMID- 2927714 TI - Effects of synchrony between primate corticomotoneuronal cells on post-spike facilitation of muscles and motor units. AB - Cross-correlating the activity of neighboring motor cortex neurons recorded with independent electrodes in behaving monkeys has revealed synchronization peaks, largely due to common synaptic input. Corticomotoneuronal (CM) cells produced post-spike facilitation (PSF) of rectified forearm electromyograms (EMG); 15 cells synchronized with CM cells showed no PSF. Five pairs of CM cells with overlapping muscle fields exhibited similar synchrony peaks. The contribution of this synchrony to facilitation of common target muscles was assessed by two new methods: selective spike-triggered averaging and convolution. They showed that the PSF is composed predominantly of effects mediated by output of the triggering cell, but may include a broad, shallow component mediated by synchrony with other CM cells. PMID- 2927715 TI - Electron microscopic localization of cholinergic terminals in the rat substantia nigra: an immunocytochemical study. AB - The presence of cholinergic terminals in the substantia nigra (SN) of the rat was investigated under the electron microscope using a monoclonal antibody against choline acetyltransferase (ChAT), the acetylcholine (ACh)-synthesizing enzyme, following the unlabelled antibody peroxidase-antiperoxidase (PAP) procedure. ChAT immunoreactive terminals were found making synaptic contacts with unlabelled dendrites in the SN pars compacta (SNC). Synaptic contacts established between cholinergic boutons and immunonegative dendrites were observed in serial sections to be of asymmetric type. The unlabelled postsynaptic dendrites to immunoreactive terminals displayed similar morphological aspects to typical dopamine-containing dendrites of the SN. Results of this study provide fine ultrastructural neurochemical support for the existence of a cholinergic innervation of the rat SNC and are consistent with the reported excitatory action of ACh on SNC dopaminergic neurons. PMID- 2927716 TI - Development of somatostatin-like immunoreactivity in the hippocampal formation of normal and reeler mice. AB - Using antisera directed against somatostatin-28 or somatostatin-28(1-12), the development of somatostatin-like immunoreactivity (SS-LI) was examined in the hippocampal formation of normal and reeler mice. As early as postnatal day 5, SS labeled neurons exhibit the adult pattern of distribution in the normal hippocampal formation, these neurons being situated predominantly in the stratum oriens of the hippocampus and the hilus of the dentate gyrus. In contrast, SS labeled neurons in the reeler hippocampal formation are dispersed throughout the various layers, reflecting the disrupted laminar organization of the hippocampus in this mutant. In both the normal and reeler hippocampal formation, SS-labeled fibers are most abundant in the stratum lacunosum moleculare. However, in the reeler, there appears to be increase in the density of SS-LI fibers, not only in the stratum lacunosum moleculare but also in the stratum oriens, stratum radiatum and pyramidal cell layer of the hippocampus. PMID- 2927717 TI - Distinct afferents to internal and external pallidal segments in the squirrel monkey. AB - The use of retrograde fluorescence double-labeling method has revealed that the internal (GPi) and external (GPe) segments of globus pallidus in squirrel monkey receive projections from different cell populations in striatum and subthalamic nucleus. Striatal neurons projecting either to GPi or GPe formed wide and nonoverlapping cell bands oriented obliquely and covering large portions of putamen and caudate nucleus. Subthalamic neurons projecting to GPe were more abundant and more laterally located than those projecting to GPi. A few cells branching to GPi and GPe were found in subthalamic nucleus but not in striatum. Thus, different striatal and subthalamic neuronal populations influence GPi and GPe in primates. PMID- 2927718 TI - Neural substrates for long-term habituation of the acoustic startle reflex in rats: a 2-deoxyglucose study. AB - Autoradiography with [14C]2-deoxyglucose was used to examine the functional activity of the rat brain during long- and short-term habituation of the acoustic startle reflex. Long-term habituated rats, when compared to short-term rats, showed an enhanced metabolic activation of the auditory system, with the exclusion of thalamocortical levels. Regional metabolic increases were also located within the cerebellum and its major input-output structures. In contrast, the midbrain reticular formation and its ascending thalamocortical activating system showed a widespread metabolic suppression. The findings provide the first map of structures in a mammalian brain with learning-related metabolic alterations dependent on long-term habituation. PMID- 2927719 TI - Dopaminergic cells in the superior cervical ganglion of the rat: light and electron microscopic study using an antibody against dopamine. AB - So-called small intensely fluorescent (SIF) cells were visualized immunohistochemically using a newly developed anti-dopamine (DA) serum in the rat superior cervical ganglia (SCG), both light and electron microscopically. Specificity of the anti-DA serum was tested in a control test and enzyme-linked immunosorbent assay (ELISA). DA-immunoreactivity was found in a subpopulation of SIF cells, but not in principal neurons. Ultrastructurally, DA-immunoreactivity was noticed in the cytoplasmic matrix and vesicles of perikarya, dendritic processes and terminals of SIF cells. DA-labeled terminals made symmetrical synaptic contacts with unlabeled principal neurons. These findings provide a morphological basis for the role of dopaminergic SIF cells as interneurons. PMID- 2927720 TI - Distribution of terminals of thalamocortical fibers originating from the ventrolateral nucleus of the cat thalamus. AB - Anterograde labelling following focal injections of Phaseolus vulgaris leucoagglutinin was used to identify the threedimensional cortical distribution of thalamocortical (TC) fibers from the ventrolateral nucleus of the thalamus of the cat. The labelled TC fibers were distributed usually in layers I and III of the motor cortex and the terminals in layer III tended to aggregate into patches about 1-1.5 mm wide in a mediolateral direction. These patches were arranged in longitudinal strips about 2-5 mm long in a rostrocaudal direction and were separated by gaps of terminal free area. PMID- 2927721 TI - Proton-induced chloride current and voltage-activated Na+ and Ca2+ currents in embryonic neurons from the medicinal leech (Hirudo medicinalis). AB - Voltage-activated ionic currents and currents induced by step changes in proton concentration (pH 7.9-6.7) were studied in early embryonic neurons from Hirudo medicinalis. Ganglia were dissociated at embryonic day (E) 8-15, and the largest neurons were investigated using whole-cell patch clamp recording. All cells studied displayed voltage-activated Na+ and Ca2+ currents. Step changes in pH induced sustained currents which reversed at the equilibrium potential for Cl- and were blocked by substituting Cl- with acetate or sulfate. These currents thus differ in their ion selectivity from proton-induced currents in vertebrate neurons which are carried by Na+. PMID- 2927722 TI - Age-related changes in regional patterns of blood-brain barrier breakdown during epileptiform seizures induced by pentylenetetrazol. AB - Age related changes in blood-brain barrier (BBB) permeability to macromolecules were investigated during seizures induced by pentylenetetrazol in rats aged from 6 to 120 days. Evans blue was used as a visual indicator of BBB integrity. BBB leakage due to seizures was present only in animals in which the mean arterial blood pressure (BP) rose with the seizure onset. Although considerable BBB damage was found partly in similar areas in young and adult rat brains, in adults the leakage of Evans blue was most intense in preoptic area, colliculus inferior, hypothalamus and cerebellum whereas the BBB opening was comparatively rare, in the same areas of young brains. In 6- and 15-day-old rats which did not differ in BP changes from the adults, the leakage was extremely intense in hypothalamus and hippocampus and in contrast to 30- or 120-day-old rats there was no leakage of Evans blue in preoptic area and cerebral cortex. From the results obtained, the conclusion may be drawn that the brain regions which are vulnerable to seizures induced by pentylenetetrazol differ markedly in developing and adult rats. On the other hand, in adult animals, either certain brain areas are more vulnerable to pentylenetetrazol or the BBB has an increased fragility particular to seizure activity. These results indicate that the sensitivity of BBB mechanisms may depend on proliferation of capillaries and changes in their internal structure and may emphasize it. PMID- 2927723 TI - Enhancement by haloperidol of the locomotor response induced by naloxone in morphine-treated guinea pigs. AB - Guinea pigs given naloxone hydrochloride, 15 mg/kg subcutaneously (s.c.) 2 h after a single dose of morphine sulphate, 15 mg/kg s.c. exhibit a withdrawal response which is characterized by a marked increase in locomotor activity. In this study the effects of haloperidol on the morphine locomotor withdrawal response of guinea-pigs were investigated. Locomotor activity was measured in a cage fitted with a single infra-red photocell and detector. Haloperidol, at a dose of 1 mg/kg, s.c., given 0.5 h prior to administration of naloxone slightly enhanced the morphine locomotor withdrawal response, and at a dose of 10 mg/kg, markedly enhanced the response. Chronic pretreatment of guinea pigs with haloperidol, 1 mg/kg, daily for 21 days did not alter the locomotor withdrawal response. It remains to be established whether the enhancement by haloperidol of the opiate withdrawal response is a functional reflection of its interaction with dopamine, sigma or other receptors. PMID- 2927724 TI - Age-dependence of the solubility fractions of acetylcholinesterase in the cerebral cortex and cerebellum of the rat. AB - Choline acetyltransferase (ChAT) activity in the cerebral cortex and the different solubility fractions of acetylcholinesterase (AChE) in the cerebral cortex and cerebellum were investigated in rats of different ages. ChAT activity was not decreased markedly in the cerebral cortex of 24- to 25-month-old rats compared to 3- to 4-month-old rats. The activity of detergent-soluble (DS) AChE in the cerebral cortex and cerebellum was lower in the older rats (24-25 months) rats than in younger (3-4 months) ones. The activity of DS-AChE in the cerebral cortex and cerebellum did not differ between 10- to 11-month-old and 24- to 25 month-old rats. The activity of low salt soluble (LSS) AChE in the cerebral cortex and cerebellum did not differ between older and younger rats. PMID- 2927725 TI - Feeding or exposure to food odors increases extracellular DOPAC levels (as measured by in vivo voltammetry) in the prefrontal cortex of food-deprived rats. AB - The effects of feeding or of exposure to food odors (without opportunity to feed) on dopamine metabolism in the prefrontal cortex have been investigated in rats food deprived for 24 h. Dopamine metabolism was assessed by measuring extracellular DOPAC levels by in vivo voltammetry with carbon fiber electrodes. Feeding in fasted rats was accompanied by an increase in extracellular cortical DOPAC levels which gradually returned to basal levels within 90 min after the onset of meal. A similar, though slightly less pronounced, increase in cortical dopamine metabolism was found in fasted rats exposed to food odors but not allowed to feed. These results indicate that feeding or the olfactory stimulation associated with food presentation causes an increase in mesocortical dopaminergic neuron activity. PMID- 2927726 TI - Nursing's image and the future. PMID- 2927727 TI - Curriculum revolution: reconceptualizing clinical nursing education. PMID- 2927729 TI - When national health insurance comes: where will nursing be? PMID- 2927728 TI - Losses and laughter. PMID- 2927730 TI - Nursing patterns of knowing and feminist thought. PMID- 2927731 TI - Independent and dependent paths: the fundamental issue for the nursing profession. PMID- 2927732 TI - Classifying nursing diagnoses: a self-care approach. PMID- 2927734 TI - "Terminal" is a relative term. PMID- 2927733 TI - Ethics and values in nursing: are we opening Pandora's box? PMID- 2927735 TI - Collaborative research: process and measurement. PMID- 2927736 TI - A textbook coding tool. Part 2. Assessing nursing textbooks. PMID- 2927737 TI - A comparison of two approaches to empathy training. PMID- 2927738 TI - Index for nursing faculty evaluation. PMID- 2927739 TI - Growing pains: faculty stages in adopting a nursing model. PMID- 2927740 TI - Care plans, clinical, and away games: helping the student nurse athlete. AB - How can students successfully blend the rigorous academic, physical, and emotional demands of nursing education and athletics? Based on survey results, the author discusses problems faced by nursing student athletes and suggestions made by faculty for resolving problems. PMID- 2927741 TI - Preparing the academic dossier. AB - Do you understand the purpose and potential power of a dossier? Understanding how to organize and present a dossier is an essential commodity in the academic community. For nurse educators who do not have a dossier, the author reviews its importance and presents guidelines for its development. For nurse educators who maintain a dossier, the author presents ideas for its refinement. PMID- 2927742 TI - Baccalaureate to MSN: an accelerated pathway for second degree students. AB - While most nursing schools are experiencing declining enrollment, the author's baccalaureate nursing program saw an increase in applications from one group of people--those with non-nursing degrees. Realizing the value of this group to nursing and the department, the author describes how an accelerated master's degree pathway was developed and implemented for those with degrees in non nursing fields. PMID- 2927744 TI - Students can enhance writing skills while promoting health. PMID- 2927743 TI - Remembering and sharing through poetry writing. AB - Reminiscing may have therapeutic outcomes for the elderly. In this article, the author describes how nursing students used poetry writing to stimulate reminiscence in group work with the elderly. The outcomes included reciprocal benefits for both the students and the elderly participants. PMID- 2927745 TI - Questioning the Tyler model? PMID- 2927746 TI - Research teaching strategies. PMID- 2927748 TI - How meaningful are course titles? PMID- 2927747 TI - Developing scientific relationships through leadership. PMID- 2927749 TI - Caffeine restriction as initial treatment for breast pain. AB - The effects of methylxanthines (caffeine, theophylline and theobromine) on the symptoms associated with fibrocystic breast disease were studied in 147 patients. Disease was documented by mammography, physical examination and clinical symptoms. Only those individuals with breast pain (n = 138) were included in the study. Questionnaires were presented and explained to all patients by the same nurse examiner. Patients reported their degree of caffeine consumption as either light (two cups per day or less of caffeine-containing beverages or foods), moderate (more than two cups, but less than six cups per day), or heavy (six cups per day or more of caffeine-containing products). They additionally reported breast pain as mild, moderate or severe. Past medical and family histories were reported as well as medication intake. All patients were counseled to abstain from or reduce caffeine consumption and were given a list of commonly used caffeine-containing products. The results at the end of one year indicated that compliance was high, with 113 patients (81.9 percent) reducing their caffeine intake substantially and, of those, 69 (61 percent) reporting a decrease or absence of breast pain. This study supports the findings of others in that caffeine restriction is an effective means of management of breast pain associated with fibrocystic disease. PMID- 2927750 TI - Tips on writing successful grant proposals. AB - Writing a grant proposal is both a means of obtaining research funds and of clarifying and developing a research project. When developing and writing a grant proposal, the applicant must consider the criteria used by funding agencies in its evaluation: expertise of the applicant, the research question, knowledge of the field, soundness of the research design, relevance, ethics and budget. Addressing these criteria will assist the applicant in developing an effective grant proposal. Applicants should also target their proposal to all agencies that have an interest in the field of the research. Alternative sources of research funds, such as private foundations, should be explored whenever possible. If an application is not funded, the researcher should use the reviewers' comments to improve the proposal for the purpose of resubmission. This article discusses some of the basics of preparing and submitting a grant proposal to funding agencies in order to obtain support for nursing research. PMID- 2927751 TI - Nurses' involvement in smoking cessation. PMID- 2927752 TI - Disorders of excessive daytime sleepiness. AB - The complaint of excessive daytime sleepiness (EDS) is associated with a number of disorders. The frequently disabling symptoms of EDS are just beginning to be addressed. This article offers nurse practitioners background information to help in evaluating EDS symptoms. Disorders related to the physiological need for sleep and the response to disrupted sleep or the effect of psychobiological sleep disruption are presented. Differential diagnoses are reviewed and keys to case management are offered. The management of sleep disorders may involve a collaborative role with other health professionals in order to provide optimal patient care. To assist the NP in referring the patient to specialized care, referral services are described. PMID- 2927753 TI - The 'window phase' of HIV. PMID- 2927754 TI - An act of love, not betrayal. PMID- 2927755 TI - Death & dying. PMID- 2927756 TI - Strangulation. PMID- 2927757 TI - Head-injured patients: how to detect early signs of trouble (continuing education credit). PMID- 2927758 TI - Letting the family in during a code. PMID- 2927759 TI - Letting the family in during a code. A trauma nurse's opinion. PMID- 2927760 TI - Letting the family in during a code. Legally, it makes good sense. PMID- 2927761 TI - Performing CPR on infants. PMID- 2927762 TI - Practical ways to assert yourself. PMID- 2927763 TI - Pressure sores: dressed for successful healing. PMID- 2927764 TI - Solving bioethical dilemmas: a practical approach. PMID- 2927765 TI - At night they cry. PMID- 2927766 TI - Grunting respirations: sure distress. PMID- 2927768 TI - Skin care: managing breakdown. PMID- 2927769 TI - Toileting patients: lifting aid. PMID- 2927767 TI - Mrs. McGiver's collapse--unmasking the true cause. PMID- 2927770 TI - Adverse drug reactions: reaching the F.D.A. PMID- 2927771 TI - Home care: how to support family caregivers. PMID- 2927772 TI - To Bobby, with love--and thanks. PMID- 2927773 TI - When a patient's scheduled for G.I. studies. PMID- 2927774 TI - Myths & facts about myocardial infarction. PMID- 2927775 TI - Managing emergencies. PMID- 2927776 TI - [A first in the drug industry--the underpinnings of a pill]. PMID- 2927777 TI - [Cognitive disorders in the elderly patient]. PMID- 2927778 TI - [Arthritis]. PMID- 2927779 TI - [How do you record your observations?]. PMID- 2927781 TI - Behavioral alert. PMID- 2927780 TI - [Nursing care for patients with severe burns]. PMID- 2927782 TI - [Children of AIDS]. PMID- 2927783 TI - [The nursing profession in the northern regions of Canada]. PMID- 2927784 TI - [The Department of Health and Social Services: plan of action against AIDS: phase II]. PMID- 2927785 TI - [Beyond the code of professional conduct]. PMID- 2927786 TI - Qualitative research: publishing and funding. PMID- 2927787 TI - Philosophical ponderings on qualitative research methods in nursing. AB - This article focuses on the philosophical underpinnings of qualitative research methods. The historical context reflects an interpretive turn from envisioning nursing as a natural science to one of a human science. The phenomological paradigm is reflected upon in the questioning of perception, philosophy, nursing philosophy, paradigms, assumptions, and praxis. An invitation to embrace human understanding of experience, meaning of life worlds, the essences of experience, the attentive practice of thoughtfulness, and caring attunements is extended. The aims of discovery and qualitative research methods are presented within social, experiential, linguistic, and cultural contexts. In a fundamental sense, this paper is about the meaning and seriousness of human experience and nursing's efforts to study such experience faithfully, with reverence and wonderment. PMID- 2927788 TI - The relentless drive to be ever thinner: a study using the phenomenological method. AB - The relentless drive to be thinner is an experience lived by many individuals in the present sociohistorical context. Since fundamental questions concerning the structure of this lived experience remain unanswered in the literature, theory based approaches to nursing practice have yet to be conceptualized for these individuals. The investigator was unable to find even a single nursing study related to the target phenomenon. The present study addresses the foundational question: What is it like to live the experience of the relentless drive to be ever thinner? Retrospective written and verbal accounts from two women who had lived this experience were analyzed using the Giorgi modification of the phenomenological method. The central finding of this study was: The relentless drive to be ever thinner is a persistent struggle toward an imaged self lived through withdrawing-engaging. This theoretical proposition was found to be congruent with Parse's theory of nursing. The study findings suggest directions for innovative nursing practice and support Parse's theory as a useful perspective for the investigation of health experiences. PMID- 2927789 TI - Qualitative findings: what to do with them? PMID- 2927790 TI - The lived experience of recovering from addiction: a phenomenological study. AB - The purpose of this study was to evolve a structural description of the experience of recovering from addiction. The phenomenological method was chosen for the study. The sample consisted of three subjects recovering from addiction. The subjects were asked to write a description of a situation in which they were aware of recovering from their addiction. Each subject was then interviewed to elaborate on portions of the written description. The phenomenon, recovering from addiction, emerged from the findings of this study as a lived experience of struggling to pull self out of a well of darkness into the comfort of light. This is experienced as the person lives profound shifts in ways of being. As these shifts rhythmically move the person toward openness to the light of possibilities, the person chooses to move beyond with comfort and trust in the negentropic process of becoming. The findings of this study support the value of the phenomenological method for nursing research and the nursing theory, man living-health. The results of this study also support nursing practice as a healing relationship illuminating meaning in situations and mobilizing choices in the negentropic process of becoming. PMID- 2927791 TI - Standards for qualitative research. AB - One of the greatest obstacles to the identification of excellence in qualitative studies is the lack of generally accepted criteria. The criteria developed for quantitative studies are based on a different set of assumptions and are not appropriate. Those who critique qualitative studies need context flexibility, skills in inductive reasoning, skills in theory analysis, and the capacity to transform ideas across levels of abstraction. The following standards are proposed for critique of qualitative studies: (a) descriptive vividness; (b) methodological congruence; (c) analytic preciseness; (d) theoretical connectedness; and (e) heuristic relevance. Methodological congruence has four elements: rigor in documentation; procedural rigor; ethical rigor; and auditability. Heuristic relevance has three elements: intuitive recognition; relationship to existing body of knowledge; and applicability. Threats to each of these standards are identified. Creative strategies for improving the published presentation of qualitative studies must be developed to allow adequate critique. PMID- 2927792 TI - Qualitative research: a process of discovery. PMID- 2927793 TI - Phenomenological research in nursing: commentary and responses. PMID- 2927794 TI - The role of selenium deficiency in occidental dilated cardiomyopathy. AB - The whole blood selenium concentrations were measured in 14 consecutive cases of catheter-proven dilated cardiomyopathy. The mean range of selenium was 59 ng/mL (SD 14). Patients with coronary heart disease had a mean value of 44 ng/mL (9.7) and normal controls had 78 ng/mL (20.1). These results would not support the hypothesis that selenium deficiency is an important causative agent in dilated cardiomyopathy in New Zealand. PMID- 2927795 TI - Who comes back to a paediatric outpatient clinic? AB - Over a four week period, 498 children had appointments to be seen again at a paediatric medical outpatient clinic. 15.8% of the patients did not keep their appointments. The three most common types of disorder accounting for over half the consultations were asthma, neurological/developmental problems and genitourinary conditions. Over half (57%) had been referred within the previous two years, and only 29% had been seen for three or more years. Involvement with other medical and paramedical specialists occurred in 55%. This reflected the multidisciplinary management approach for the longer term patients. Only 14 new such referrals were generated as a result of the consultations over the four week study period. The work of the clinic was concerned with relevant chronic disease. PMID- 2927796 TI - Trends in private medical insurance ownership: lessons for the public sector. AB - Data on ownership of private medical insurance were collected from a fully national sample of over 1000 adults. Findings were compared with those of a study undertaken in 1981. Private medical insurance was owned by 40% of the sample, an increase from the 35% ownership in the earlier study. The increase has been predominantly amongst nonMaori New Zealanders and women have increased ownership more than men. Insurance ownership was most common amongst the middle age group (36-50 years) but it has increased significantly amongst the older groups. Greatest areas of growth in ownership were in Auckland and Wellington where proportionate ownership was 52% and 50% respectively. Medical insurance was employer provided amongst 15% of those with insurance, the same proportion as found in the earlier study. Employer subsidy to insurance was evident also. Major reasons to take out insurance were for primary care purposes, so as to overcome the cost barrier to general practitioner services. Other reasons mentioned included avoidance of waiting for treatment and increase in choice of specialist or hospital. Reasons for giving up insurance were cost of premium, disillusionment with benefits and disqualification through age or illness. PMID- 2927797 TI - A standard for ethical committees. PMID- 2927798 TI - The scientific method. PMID- 2927799 TI - Sickness absenteeism and smoking. PMID- 2927800 TI - Autopsy and the cause of death. PMID- 2927801 TI - Bed needs in psychiatry. PMID- 2927802 TI - The O & G Society: an experiment in postgraduate education. PMID- 2927803 TI - Cervical cancer in Pacific island Polynesians. PMID- 2927804 TI - Acute renal failure in a critical care unit. AB - We have reviewed all patients in a critical care unit who required dialysis for acute renal failure during a five year period from 1981-5. There were 45 patients, all of whom were severely ill, the majority requiring mechanical ventilation. Twenty-five were classified as surgical, including trauma, eighteen medical and two obstetric. The overall mortality rate was 53%. A wide range of variables were reviewed and it was found that only the number of failed organs was a significant predictor of mortality. Progressive multiple organ failure in turn was associated with ineradicable sepsis in the majority, although in 25% of deaths with multiple organ failure, sepsis was not proven. Patients without sepsis or multiple organ failure had excellent survival. Further reductions in the acute renal failure mortality rate will depend on better methods of prevention, diagnosis, and management of sepsis. PMID- 2927805 TI - The diagnosis of sexual abuse of children. PMID- 2927806 TI - Reasons for racial differences in A & E attendance rates for asthma. AB - To determine whether racial differences in the severity of asthma accounted for the higher accident and emergency department (A & E) use by Pacific Islanders and Maoris, a study of A & E users at Middlemore Hospital and of asthmatics using urgent medical services was undertaken. Europeans reported more daytime symptoms of asthma (p less than 0.0005) and were on more medications (p less than 0.005) than Pacific Islanders, with Maoris intermediate (ns). Relative to the perceived severity of their asthma, both Maoris and Pacific Islanders lost more time from work or school and used hospital services more than European asthmatics using A & E. The increased use of A & E by Maori and Pacific Island asthmatics seemed not attributable to the intrinsic severity of their asthma and was better explained by ethnic, socioeconomic and sociocultural factors. Pacific Islanders had less self management skills and, like Maoris, were less likely to be on prophylactic medications relative to oral bronchodilator use and these factors likely contributed to their increased morbidity. PMID- 2927807 TI - The validity of Maori mortality statistics. AB - Data from an Auckland coronary heart disease register have been used to assess the validity of Maori mortality statistics produced by the National Health Statistics Centre. During the period 1983-4, 804 people aged 35-64 years and resident in the Auckland statistical region, were identified by both the register and death registration data as having died of coronary heart disease. The coronary heart disease register failed to classify the ethnicity of thirteen of these people. Of the remaining 791 cases, the register classified 80 as Maori while only 44 were classified as Maori in the national death registration data; over the period 1983-4 Maori mortality due to coronary heart disease in the Auckland statistical region was understated by 82% (80-44/44). Although some of this discrepancy may be due to differences in classification of ethnicity, the major reason for the understatement is missing information on the death registration form. Simple changes in the documentation of ethnicity could markedly reduce the degree of underreporting. PMID- 2927808 TI - Nondiscocytic erythrocytes in myalgic encephalomyelitis. AB - Blood samples from 102 volunteers who believed they suffered from myalgic encephalomyelitis were photographed in a scanning electron microscope at 500x. All identifiable cells were counted and classified on the basis of their shape. The frequency of each cell shape was expressed as a percentage of the total number of cells counted in the sample. The resulting data were compared with that from 52 healthy controls and 99 cases of multiple sclerosis which had been selected randomly by a computer from a panel of 229 cases in a concurrent study. Samples from subjects with myalgic encephalomyelitis had the lowest percentages of normal red cells and the highest incidence of cup forms. The results provide evidence that myalgic encephalomyelitis has an organic cause. Quantitative analysis of red cell shape may assist in the diagnosis of myalgic encephalomyelitis. PMID- 2927809 TI - Recent general practice contacts of hospitalised suicide attempters. AB - This study investigated the timing of recent medical contact in 150 patients hospitalised for a suicide attempt. The research also examined the proportion of attempters complaining of feeling depressed or suicidal to their doctor at that recent consultation. Seventy-three percent of attempters had seen their doctor in the past three months. Contact with general practitioners was most common in the week before their attempt with 32% of all attempters visiting their doctor during this time and 56% visiting in the previous month. Of those attempters who had consulted their general practitioner prior to their attempt, only 35% had complained about feeling depressed or suicidal to their doctor. Several factors that hinder the successful identification of suicidal risk in the general practitioner-patient relationship are identified. The implications of these findings for suicide prevention are discussed. PMID- 2927811 TI - Diving medicals. PMID- 2927810 TI - Quality of outcome and cost in an obstetric and neonatal service. AB - A review has been made of the outcome and efficiency of the obstetric and neonatal service, St Helen's Hospital, Auckland. In the last seven years there has been a 33% fall in perinatal mortality rates to 5.88 per 1000 births in 1987. The average perinatal death rate for Maori infants was low, 4.81 per 1000 compared to 7.43 per 1000 for Europeans over this period. There has been a 38% increase in births to 3597 a year while the total hospital staffing has only risen 9%. Thus the ratio of births to staff has increased by 26.6% to 15.6. The cost per infant delivered in constant dollars has fallen 18.7% in the same period to $2432. The postnatal bed occupancy was 101% in 1987 and the average day stay fell to 5.7 days. An extra 61 full time staff would be needed to reduce the workload to that of 1981 and the staff is now unable to give the family focused holistic care that is needed. PMID- 2927812 TI - Medical research--who minds the minders? PMID- 2927813 TI - Referral by general practitioners to specialists in other board areas. PMID- 2927814 TI - General practitioner services. PMID- 2927815 TI - Cot deaths. PMID- 2927816 TI - Bed needs in psychiatry. PMID- 2927817 TI - Drugs in sports. PMID- 2927818 TI - Markets revisited. PMID- 2927819 TI - Alternative medicine. PMID- 2927820 TI - Theory Z may reduce turnover. PMID- 2927821 TI - An expert answers common questions about primary nursing. PMID- 2927822 TI - Professional nursing case management improves quality, access and costs. PMID- 2927823 TI - Case-managed care: capitalizing on the CNS. PMID- 2927825 TI - Marketing private duty services. PMID- 2927824 TI - Reliability of the nursing classification index for home healthcare. PMID- 2927826 TI - Empathy training: development of sensitivity and caring in hospitals. PMID- 2927827 TI - The Army nursing care team. PMID- 2927828 TI - Recording end of life directives on hospital admission. PMID- 2927829 TI - The news from the front ... PMID- 2927830 TI - The prestige of today's nurse. PMID- 2927831 TI - Correction please! PMID- 2927832 TI - Disease-specific isolation: the alternate method. PMID- 2927833 TI - Fee schedule and direct billing for CRNA services. PMID- 2927834 TI - Vulnerable no more. PMID- 2927835 TI - What the nurses know. PMID- 2927836 TI - Case-based prospective price reimbursement. PMID- 2927837 TI - Hospital-based SNFs improve the bottom line. PMID- 2927838 TI - Multis, mergers, acquisitions and the healthcare provider. PMID- 2927839 TI - Initiating a diabetic center. PMID- 2927840 TI - Conflict in the operating room. PMID- 2927841 TI - Obstacles to collaborative practice. PMID- 2927842 TI - Forensic odontology and the identification of human remains. AB - The forensic odontology discipline has proven to be another extremely important avenue of dentistry's service to mankind. Only the deeply committed, knowledgeable and skillful dental professional can provide this service and it cannot be duplicated. Scientific investigation leading to continual improvements in the techniques of identification as well as the other facts of forensic odontology are typical of dental professionalism and service. PMID- 2927843 TI - Forensic odontology and mass disasters. PMID- 2927844 TI - The dentist, forensics and the law. PMID- 2927845 TI - Bite mark evidence. Recognition, preservation, analysis and courtroom presentation. PMID- 2927846 TI - Forensic odontology serving modern society. PMID- 2927847 TI - Computer advice. PMID- 2927848 TI - A bit of plagiarism or JFK updated. PMID- 2927849 TI - Quantitative hemodynamic effects of acute volume expansion in severe preeclampsia. AB - In a study of eight patients with severe preeclampsia, cumulative rapid infusions of 500 mL (set of eight patients) and 1000 mL (subset of five patients) of 5% albumin in normal saline were followed with invasive hemodynamic measurements at 5 and 30 minutes. Pulmonary capillary wedge pressure and central venous pressure rose. Cardiac index rose 23 and 34% at 5 minutes after the 500-mL and 1000-mL infusions, respectively; at 30 minutes, it remained at 17 and 34%, respectively, above control. The systemic vascular resistance index fell 24 and 29% below control values at 5 minutes after the respective infusions; at 30 minutes, it remained at 15 and 25%, respectively, below control. Mean systemic arterial pressure was unchanged, except for a small reduction shortly after the initial 500-mL infusion. In contrast, mean pulmonary arterial pressure rose significantly. Hence, the dominant effects of acute volume expansion in severe preeclampsia include an unchanged (or slightly reduced) mean systemic arterial pressure, resulting from marked elevations in cardiac index and concomitant, proportionate declines in systemic vascular resistance index. PMID- 2927850 TI - Puerperal uterine inversion. AB - A 10-year retrospective study of acute puerperal inversion of the uterus was undertaken at Women and Infants Hospital of Rhode Island. There were 11 inversions in 70,481 deliveries for an incidence of one in 6407. The age ranged from 19-31 years. Seventy-three percent occurred in nulliparous women. All cases were recognized immediately, and vaginal replacement was successful in nine patients. One patient had a placenta accreta necessitating a supracervical hysterectomy, and one patient required a laparotomy and Huntington procedure for replacement. Six patients had blood loss greater than 1000 mL and three required transfusion. There were no maternal deaths. PMID- 2927851 TI - Logistic regression analysis of risk factors for intra-amniotic infection. AB - The identification of risk factors for intra-amniotic infection may allow changes in obstetric management and reduce complications. In a pilot study, stepwise logistic regression identified duration of ruptured membranes and duration of interval monitoring as significant risk factors for intra-amniotic infection. Using the preliminary regression equation, we established critical durations (risk criteria) to predict a 20% or greater probability of intra-amniotic infection. Subsequently, 2908 patients were screened prospectively for risk criteria and/or the presence of intra-amniotic infection. Seven hundred five patients of the 2908 (24%) met the risk criteria, and 107 of 124 cases of intra amniotic infection (86%) met the risk criteria. In patients meeting the risk criteria, the relative risk of intra-amniotic infection was 19.7. In addition, 81 of 705 (12%) of mothers developed endometritis. Ten neonates of mothers with criteria developed sepsis or pneumonia. A stepwise logistic regression performed on the prospectively gathered data showed that among patients meeting risk criteria, parity, duration of internal monitoring, and duration of membrane rupture were the significant risk factors for intra-amniotic infection. PMID- 2927852 TI - Meta-analysis of the relationship between asymptomatic bacteriuria and preterm delivery/low birth weight. AB - The relationship between asymptomatic bacteriuria and prematurity/low birth weight (LBW) is still a controversial issue, despite many studies. Meta-analysis, a research tool designed to analyze and combine the results of previous studies, may resolve this discrepancy among contradictory results of clinical trials. The purpose of this study was to examine the relationship between asymptomatic bacteriuria and preterm delivery/LBW using meta-analysis. Reports from the literature were classified according to study design into cohort or randomized treatment control trials. Meta-analysis of cohort studies showed that untreated asymptomatic bacteriuria during pregnancy significantly increased rates of LBW and preterm delivery. Nonbacteriuric patients had only about two-thirds the risk (typical relative risk = 0.65; 95% confidence interval 0.57, 0.74) of LBW and half the risk (typical relative risk = 0.50; 95% confidence interval 0.36, 0.70) of preterm delivery of those with untreated asymptomatic bacteriuria. These reduced risks correspond to a 3.4 (confidence interval 1.8, 5.0) percentage-point difference in LBW and a 3.8 (1.1, 6.4) percentage-point difference in preterm delivery. The analysis of randomized clinical trials showed that antibiotic treatment significantly reduced the risk of LBW (typical relative risk = 0.56; 95% confidence interval 0.43, 0.73), with a substantial reduction of 6.4 (confidence interval 3.3, 9.5) percentage points in the rate of LBW. We conclude that clinical and epidemiologic evidence indicates a strong association between untreated asymptomatic bacteriuria and LBW/preterm delivery and that antibiotic treatment is effective in reducing the occurrence of LBW. PMID- 2927853 TI - The effects of lactation on bone mineral content in healthy postpartum women. AB - Bone mineral contents were estimated by dual photon absorptiometry of the lumbar spine (L2-L4) and single photon absorptiometry of the mid- and distal radius in 19 healthy women on their second postpartum day and at 6 months postpartum. All bone mineral measurements were performed by one technician, and the single and dual photon absorptiometry results were read by one observer. Daily oral calcium intakes were estimated from dietary histories obtained by a dietitian. Twelve women who breast-fed exclusively throughout the first 6 months postpartum were compared with seven formula-feeding women who did not breast-feed or who breast fed for less than 3 months postpartum. No differences were found in age, parity, height, weight, or daily calcium intake between the breast- and formula-feeding women. Breast-feeding women had a significant decrease (averaging 6.5%) in bone mineral of the lumbar spine at 6 months postpartum as compared with 2 days postpartum (1.14 +/- 0.03 versus 1.22 +/- 0.03 g/cm2, mean +/- SEM; P less than .001), whereas no significant change occurred in the formula-feeding women at 6 months (1.24 +/- 0.03 versus 1.26 +/- 0.04 g/cm2). At 6 months postpartum, the breast-feeding women had a significantly lower mean bone mineral content of the lumbar spine than did formula-feeding women (P less than .05). No significant changes were noted in bone mineral content of the mid- or distal radius in either group of women during the period of evaluation. We conclude that during the first 6 months postpartum, breast-feeding is associated with bone mineral loss from the lumbar spine, but not from the mid- or distal radius. PMID- 2927854 TI - Complications of uterine leiomyomas in pregnancy. AB - Uterine leiomyomas are found in approximately 2% of pregnant women. One of ten women with myomas will have complications related to myomas during pregnancy. The major complication is the syndrome of painful myomas of pregnancy, characterized by second- and early third-trimester pain and occasionally bleeding. In our population, fever, rebound tenderness, and elevated white blood cell count were not associated with pain. Short courses of ibuprofen were successful in controlling pain in these women. Other complications of myomas in pregnancy included preterm premature rupture of the membranes, malpresentation, increased cesarean delivery rate, and postpartum endomyometritis. PMID- 2927855 TI - Correlation of Apgar scores and umbilical artery acid-base status to mortality and morbidity in the low birth weight neonate. AB - Neonatal mortality, idiopathic respiratory distress syndrome, and early periventricular/intraventricular hemorrhage in the neonate weighing 2000 g or less were correlated with umbilical artery acid-base status. Neonatal mortality and, to a lesser extent, idiopathic respiratory distress syndrome correlated with umbilical artery acidosis. Early periventricular/intraventricular hemorrhage was associated with low Apgar scores, but showed no correlation with umbilical artery acid-base status. PMID- 2927856 TI - Characteristics of premenstrual syndrome. AB - To characterize the symptoms associated with premenstrual syndrome (PMS), the menstrual symptom calendars of 100 women diagnosed with PMS were factor-analyzed. Scores on 18 symptoms were recorded daily for one menstrual cycle prior to the women's first clinic visits. Two factors were found to predominate throughout the cycle: The first included emotional and behavioral symptoms and the second included physical and cognitive symptoms. The two factors were constant throughout all the phases of the menstrual cycle. Emotional symptoms clustered together throughout the menstrual cycle and were the dominant symptoms on factor I. However, they loaded (correlation of the variable with the factor) on factors I and II during the postmenstrual phase. Behavioral symptoms loaded on factor I throughout the menstrual cycle; however, they were prevalent predominantly in the later half of the intermenstrual and the premenstrual phases. Physical symptoms loaded predominantly on factor II and were less prevalent than the emotional symptoms. The cognitive symptoms loaded on factor II during the premenstrual phase. These findings are relevant for defining PMS criteria for women who seek treatment. PMID- 2927857 TI - A comparison of the fallopian tube's response to overt and silent salpingitis. AB - We examined two groups of infertile women who underwent microsurgical repair of their fallopian tube(s) for distal tubal obstruction, one with a history of salpingitis (overt pelvic inflammatory disease) (N = 34) and one without (silent pelvic inflammatory disease) (N = 25). Nine women with normal tubes undergoing hysterectomy and salpingectomy served as controls. Tubal biopsy specimens were studied by light, scanning, and transmission electron microscopy to assess tubal damage. Morphologic damage was scored 0-9, with 0 representing normal tubal architecture and 9 assigned to severe tubal damage. The mean score (+/- SEM) in women with overt pelvic inflammatory disease was 4.2 +/- 0.4; in women with silent pelvic inflammatory disease, 4.3 +/- 0.4; and in the control group, 0.76 +/- 0.2 (P less than .001). Fallopian tube abnormalities seen in women with overt and silent pelvic inflammatory disease included flattened mucosal folds, extensive deciliation, and degeneration of secretory epithelial cells, morphologic changes that are similar to the cellular changes observed in our experimental Chlamydia trachomatis infections in monkeys. Laser light-scattering spectroscopy was used to measure the ciliary activity of the epithelial cells. Ciliary beat frequency was significantly reduced in women with overt pelvic inflammatory disease (N = 13; f = 6.4 +/- 1.2 Hz) and in women with silent pelvic inflammatory disease (N = 11; f = 7.2 +/- 1.2 Hz) as compared with the controls (N = 5; f = 23.4 +/- 1.5 Hz) (P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2927858 TI - Patterns of uterine contractions and prolonged uterine activity using three methods of breast stimulation for contraction stress tests. AB - The contraction patterns in 378 breast-stimulated contraction stress tests administered to 213 women are described. The subjects were assigned sequentially to one of four intervention groups: bilateral manual breast massage, unilateral pump stimulation, heating pad stimulation, and placebo. There was a marked increase in the proportion of tests with three to four contractions in 5-minute intervals after the interventions occurred. Twenty-five percent of all tests showed prolonged uterine activity, occurring most frequently in women with postdate gestations using manual massage or breast pump stimulation. The duration of prolonged contractions ranged from 1.5-8 minutes, with 19% lasting from 4.5-8 minutes. There was no difference in the incidence of fetal heart rate abnormalities between tests with and without prolonged uterine activity, and no late decelerations occurred in tests with tachysystole. PMID- 2927859 TI - Reduced fetal platelet counts in pregnancies with abnormal Doppler umbilical flow waveforms. AB - Fetal and maternal platelet counts were correlated with antenatal assessment of the umbilical-placental waveform. Forty singleton pregnancies were studied using Doppler ultrasound, and placental resistance was categorized as normal or high according to the systolic/diastolic ratio. We performed platelet counts on maternal and cord blood taken at the time of cesarean section. The high resistance group had a mean fetal platelet count (218 +/- 53 x 10(3)/microliters) significantly lower than that of the normal-resistance group (314 +/- 76 x 10(3)/microliters) (P less than .001). This difference was evident in both the hypertensive and nonhypertensive subgroups of the high-resistance group. There was no difference in mean maternal platelet counts between the high- and normal resistance groups. PMID- 2927860 TI - The prevention of meconium aspiration in labor using amnioinfusion. AB - In an effort to improve maternal and fetal outcome in patients laboring with thick meconium, 85 patients presenting with thick meconium were randomized to receive either amnioinfusion with 1000 mL normal saline initially and every 6 hours until delivery, or routine care. Meconium was discovered on initial examination during labor, after artificial rupture of membranes, through the use of an intrauterine pressure catheter, or on amniocentesis. Labor management was otherwise routine. Forceps operations and cesarean sections were for distress or failure to progress, as indicated. Patients receiving amnioinfusion had significantly fewer low 1-minute Apgar scores, less meconium below the cords, and a significantly lower incidence of operative delivery. The only three cases of meconium aspiration syndrome occurred in infants delivered of patients receiving routine management. No adverse side effects of amnioinfusion were detected. Amnioinfusion is a simple, inexpensive, and safe technique that reduces the incidence of meconium below the cords and improves obstetric outcome in patients laboring with thick meconium. PMID- 2927861 TI - Experimental meconium aspiration in guinea pigs. AB - The effects of aspirated heavy human meconium and clear human amniotic fluid on newborn guinea pig lungs were compared with the changes these solutions induced in lungs subjected to acute asphyxiation. No specific meconium-induced chemical pneumonitis was observed. Histologic changes in the form of necrosis and infiltration of the lungs were similar in pups that aspirated meconium and those that aspirated clear amniotic fluid; the only difference was in the distribution of these changes, which could be explained by the different consistencies of the two solutions. In the lungs of newborn pups that were exposed to 120 minutes of maternal asphyxia, had pH below 7.10, and aspirated the above fluids, additional dominant changes appeared in the form of diffuse intra-alveolar hemorrhage and alveolar wall destruction. These histologic studies indicate that deeply aspirated meconium does not cause the pulmonary vascular changes considered characteristic of meconium aspiration syndrome. However, aspirated meconium did affect the vascular system of the asphyxiated lungs to a significant degree. PMID- 2927863 TI - Instructional model for percutaneous fetal umbilical blood sampling. AB - Percutaneous umbilical cord sampling is gaining widespread acceptance for diagnostic and therapeutic procedures on the fetus. The sampling technique has been reported to be relatively safe in experienced hands. Attainment of the skills for this procedure follows a learning curve, with improvement in successful sampling occurring over time. This paper presents a practical instructional model for percutaneous umbilical cord sampling. PMID- 2927862 TI - Treatment of vaginal intraepithelial neoplasia with laser and topical 5 fluorouracil. AB - The records of 59 women with grades 2 and 3 vaginal intraepithelial neoplasia were reviewed to define the role of CO2 laser ablation and topical 5-fluorouracil (5-FU) in the treatment of vaginal intraepithelial neoplasia. The patients in each treatment group were comparable in their personal characteristics and in distribution and severity of the lesions. Thirty-one patients used prophylactic 5 FU. Seventy-eight percent of all patients were free of vaginal intraepithelial neoplasia at the first follow-up examination. The results of treatment were not influenced by the grade of the lesion or previous radiation exposure of the patient. Topical 5-FU appeared to be as effective as laser. Periodic applications of 5-FU (once weekly for 10 weeks) were as effective as 5-FU applied in a continuous fashion (three 7-day courses 1 week apart), and caused fewer side effects. PMID- 2927864 TI - OH Society looks ahead. PMID- 2927866 TI - Introducing cytology. PMID- 2927865 TI - An Accident & Emergency surgeon with the Antarctic survey. PMID- 2927867 TI - Is justice served? PMID- 2927868 TI - The AIDS report from the 1988 OSMA clinical and scientific meeting. PMID- 2927869 TI - Subpoenas for medical records served upon physicians. PMID- 2927870 TI - Human immunodeficiency virus seropositivity in intravenous drug users in Ohio. AB - A seroprevalence survey of 508 intravenous (IV) drug users enrolled in methadone treatment programs in Ohio for evidence of infection with the human immunodeficiency virus (HIV) demonstrated a positivity prevalence of 1.4%. This seropositivity prevalence is low compared with 10% to 72% positive from surveys conducted in the IV drug-using populations of New York, New Jersey, Detroit and San Francisco. Although needle sharing was common (71% since 1983), the number of sharing partners was usually limited and regular. A potential for cross-infection from urban centers with higher seropositivity prevalence was indicated by patterns of travel and needle sharing while traveling to higher risk metropolitan centers such as New York. Hispanics appeared to be at greater risk for HIV infection (OR 17.7, 95% CI 2.4-133.0), as were male IV drug users with gay/bisexual lifestyles (OR 14.1, 95% CI 1.3-153.0). HIV positive individuals were identified in Cleveland (1.6%), Dayton (3.1%), and Columbus (0.8%), but not in the four other Ohio metropolitan areas participating in the survey. Study participants indicated that knowledge of AIDS had changed their IV drug-using habits with 60% reporting that fear of AIDS had caused them to give up IV drugs or needle sharing. Sampling from methadone clinics may underestimate the HIV seropositivity in Ohio's IV drug-using community; however, it appears that relatively few IV drug users in Ohio are currently infected with HIV. The low prevalence of HIV infection in the Ohio IV drug-using community provides the opportunity to intervene in limiting the spread of the virus by educating individuals to reduce or eliminate risk factors for the transmission of the disease. PMID- 2927871 TI - A bad connection. PMID- 2927872 TI - Malpractice crisis: a personal perspective. PMID- 2927873 TI - Physician parents. The mothers and fathers behind stethoscopes. PMID- 2927874 TI - Training today's health professionals about AIDS. PMID- 2927875 TI - Health maintenance update: guidelines for the physician and patient. AB - In summary, we have gathered information from current sources in order to provide practicing physicians up-to-date health maintenance recommendations. We have also provided sample forms that can be used for recording information and ensuring that timely screening is accomplished. These same forms could also be given to the patient who has a desire to be involved in his/her medical care. Although some of the recommendations will remain stable over a period of time, there will certainly be new developments in medicine that will alter today's advice. Our concept is that each physician should develop and keep up to date a plan of health maintenance and screening and have some method of ensuring that appropriate screening is accomplished. PMID- 2927876 TI - Continuum of care--a practicing physician's view. PMID- 2927877 TI - Diary of my practice--1999. PMID- 2927878 TI - Endothelial cell counts following pars plana vitrectomy in pseudophakic and aphakic eyes. AB - In 13 pseudophakic eyes, endothelial cell counts remained stable following pars plana vitrectomy. The posterior chamber pseudophakos apparently had a protective effect on the corneal endothelium, even though the posterior lens capsule was removed during surgery. By contrast, in nine aphakic eyes, a statistically significant (p greater than .05) cell loss of 7.6% occurred after pars plana vitrectomy. We conclude that vitrectomy therefore poses an increased risk to the cornea in aphakic, but not in pseudophakic eyes. PMID- 2927879 TI - Macular edema in branch retinal vein occlusion: types and treatment. AB - In this study of branch retinal vein occlusion, we distinguished between cystoid macular edema caused by increased capillary pressure and noncystoid edema due to hard exudates in the macula caused by chronic leakage from vascular abnormalities in the posterior pole or midperiphery. We performed laser photocoagulation in 51 eyes with cystoid macular edema to achieve focal narrowing of the retinal arterioles perfusing the macular area affected by the cystoid edema; good anatomic and functional results were achieved in 40 of these eyes (78%). In 25 of the five eyes, the treated segment of the retinal arteriole was outside the area of macular edema; results were successful in 19 of these eyes (76%). In 14 eyes with noncystoid exudative macular edema, we performed laser photocoagulation to the vascular abnormalities; good anatomic and functional results were obtained in 12 of these (86%). PMID- 2927880 TI - Quantification of progressive diabetic macular nonperfusion. AB - We used the IS-2000 Image Analyzer to estimate the extent of progressive diabetic macular nonperfusion in a patient by means of an automatic clustering algorithm applied to digitized fluorescein angiograms of the patient's macula taken over time. This method may provide an objective and reproducible quantification of progressive macular nonperfusion. PMID- 2927881 TI - Surgical dilation of the pupil during pars plana vitrectomy. AB - Adequate pupillary dilation is essential to dissect and excise peripheral tractional proliferative tissue during vitreous surgery. Most surgical dilating procedures involve an incision or excision of iris tissue, that is either inadequate or irreversible. We describe a modification of a previously devised technique for stretching the pupil that ensures an excellent view of the peripheral retina. The technique has been used in aphakic and pseudophakic eyes in over 50 cases with no postoperative morbidity or problems with glare or poor cosmesis. PMID- 2927882 TI - Postoperative refractive changes in children with congenital esotropia: a preliminary study. AB - A transient myopic inclination was found 2 months postoperatively in 23 children who had undergone surgery for congenital esotropia. Neither the age of the children at the time of surgery nor the length of muscle recession/resection influenced these refractive myopic changes. Early postoperative refractive correction with periodic follow-up is essential in preventing amblyopia. In 21 of the 23 children, visual acuity was 6/10 or better at last examination. PMID- 2927883 TI - Use of a scalp vein infusion set in oculoplastic surgery. AB - The scalp vein infusion set is a sterile, readily available device which has been used in a variety of oculoplastic procedures. Segments of the infusion tubing have been employed as bolsters for eyelid traction, tarsorrhaphy, and skin sutures. The tubing may also be placed in wounds for improved drainage. The material has enhanced postoperative wound care and has not been associated with significant complications. PMID- 2927884 TI - Looking back or looking forward? PMID- 2927885 TI - Anesthetic abuse of the cornea. PMID- 2927886 TI - Eyelid carcinoma--another one of medicine's imitators. PMID- 2927887 TI - BAPN not lysine analog. PMID- 2927888 TI - Some objective and subjective observations on the vestibulo-ocular system. PMID- 2927889 TI - Vitrectomy when asteroid hyalosis prevents laser photocoagulation. AB - Asteroid hyalosis is a relatively common disorder of the vitreous that rarely causes visual impairment. However, funduscopic examination and laser photocoagulation can be difficult because of reflections off the asteroid bodies. Although vitrectomy is rarely indicated for impaired visual acuity, we report three cases in which pars plana vitrectomy was necessary to permit required retinal laser photocoagulation. In two patients with proliferative diabetic retinopathy and a third patient with subretinal neovascularization marked asteroid hyalosis precluded photocoagulation by standard techniques. PMID- 2927890 TI - Intermittent intraocular thrombin as an adjunct to vitrectomy. AB - The use of intraocular thrombin to control intraoperative hemorrhage is presented in two cases, one involving severe ocular trauma, the other severe proliferative diabetic retinopathy. The technique of intermittent boluses of 100 units/ml of thrombin in BSS Plus solution has certain advantages over the constant infusion mode of delivery. The ability to quickly manipulate the flow offers a distinct advantage in controlling the intraocular pressure and total amount of thrombin delivered. This is achieved by a simple and uncomplicated modification of the standard gravity infusion controlled by the surgical assistant. PMID- 2927891 TI - Prognosis of foveal splitting rhegmatogenous retinal detachments. AB - Retrospectively reviewing 4,966 patients with rhegmatogenous retinal detachments, we identified 21 patients with foveal split detachments who had no coexisting macular disease and who had been followed at least 6 months postoperatively. All detached retinas were anatomically reattached with one operation. The average preoperative and postoperative visual acuity was 20/50. Because eyes with foveal split detachments have a good visual prognosis when the retinas are anatomically reattached, we recommend that they be treated urgently, as if they had a macular spared detachment. PMID- 2927892 TI - Dacryocystorhinostomy with silicone tubes: evaluation of 253 cases. AB - Two hundred fifty-three patients with chronic epiphora underwent dacryocystorhinostomy combined with silicone intubation of the lacrimal drainage system. An overall success rate of 91.3% was achieved. Since the tubes were well tolerated postoperatively, complications were rare and benign. Although our success rate is similar to those reported for similar cases using other techniques, we find that silicone intubation facilitates surgery in cases with excessive intraoperative bleeding or nasal mucosal tears, and simplifies postoperative follow-up. PMID- 2927893 TI - The sharpness of incision instruments in corneal tissue. AB - Because breadths of surgical blades are very difficult to measure directly, we designed a method to measure sharpness of a variety of instruments by determining the power they required to incise corneal tissue to a uniform depth. Diamond knives were the sharpest, followed by razor blade pieces individually prepared by a special new method. Ruby knives varied considerably. The method of measuring sharpness described may allow manufacturers to improve and stabilize production methods, as well as enable surgeons with such knowledge in advance of surgery to optimize wound healing and maximize cost-effectiveness. PMID- 2927894 TI - A new instrument for surface suction and removal of irrigation fluid during surgery. AB - A new instrument for removal of intraocular/extraocular irrigating solutions during eye surgery, based on modification of a miniature otologic suction device, is now commercially available. PMID- 2927895 TI - Who knows how much a cataract extraction costs? . PMID- 2927896 TI - IOL power calculation. PMID- 2927898 TI - An improved method of aqueous paracentesis. PMID- 2927897 TI - Physician, do no harm. PMID- 2927899 TI - Postoperative IOP in cataract surgery. PMID- 2927900 TI - The onset of bilateral uveitis in an elderly man with fever, headache, and a rash. PMID- 2927901 TI - The gauntlet--Health care for the 1990s. PMID- 2927902 TI - Endophthalmitis due to Propionibacterium acnes sequestered between IOL optic and posterior capsule. AB - A 68-year-old woman had delayed onset, persistent uveitis following routine extracapsular cataract extraction with posterior chamber intraocular lens implantation. The patient initially responded to topical steroids, but developed a whitish capsular plaque through to represent possible Propionibacterium acnes endophthalmitis. A vitrectomy and capsular biopsy yielded cultures positive for P. acnes only after nine days. The intraocular lens was left in place. Light and electron microscopy revealed bacteria sequestered within the capsular bag. PMID- 2927904 TI - Optometry and vision science. PMID- 2927903 TI - Team approach to home health care delivery: optometry as the primary vision care provider. AB - The purpose of this report is to describe a vision care program, utilizing optometry as the primary vision care provider, for patients unable to obtain care in traditional ways. The impact of this program upon the community, its impact upon an educational curriculum, and the program itself are discussed. The program provides a model for delivery of health care to patients who would otherwise go without care. PMID- 2927905 TI - Vision care for migrant workers. AB - Migrant vision care, although encompassing only a small percentage of the population, presents a unique opportunity to the profession through the schools and practitioners. The need for care has been shown through several demonstration projects; viable practice modes have been developed that offer cost-effective care to this population. PMID- 2927906 TI - Vision care in a juvenile detention facility. AB - Optometry plays a key role in the provision of vision care services at the San Bernardino Juvenile Hall (SBJH), where 400 juvenile offenders, aged 12 to 18 years, are incarcerated. This program in San Bernardino, California, was established in 1979 by a practicing optometrist with support from federal, state, and local funding agencies. It operates as an outreach clinical program to train senior students of the Southern California College of Optometry for professional practice opportunities in a nontraditional setting. An important component of the SBJH program is an ongoing clinical research program to study the relation between vision problems and juvenile delinquency, and the effect of vision training on the rehabilitation of delinquent youths. Preliminary data indicate a reduction in the recidivism rate for this population group. PMID- 2927907 TI - Symposium on the delivery of optometric care in nontraditional settings. Summary and conclusions. AB - During the 1987 Academy Meeting, a joint Optometric Education/Public Health and Occupational Optometry Symposium was held on The Delivery of Optometric Care in Nontraditional Settings. Papers were presented on prison systems, long-term care facilities, schools for the mental/physically handicapped, home eye care services, migrant work program, and juvenile detention facilities. This paper is an overview of care delivered in nontraditional settings, including important health care and demographic considerations, brief summation of the nontraditional populations presented, the impact on optometric education, and implications for optometric manpower needs. PMID- 2927908 TI - Variations in the local refractive correction of the eye across its entrance pupil. AB - We show that normally a spherocylindrical lens will correct the local refractive error of any small area of the pupil. In general, however, the correction varies with position across the pupil. Plots are given to illustrate this variation for 2 typical individual eyes and for the average of 11 eyes, as calculated from the corresponding wavefront aberrations. The implications of these results for the design and use of objective optometers are briefly considered. PMID- 2927909 TI - Symposium on the Delivery of Optometric Care in Nontraditional Settings. Denver, Colorado, December, 1987. Proceedings. PMID- 2927910 TI - Symposium on the delivery of optometric care in nontraditional settings. Introduction. PMID- 2927911 TI - Use of silicone-acrylate contact lenses for the control of myopia: results after two years of lens wear. AB - Although a number of reports have been published concerning the use of polymethyl methacrylate (PMMA) contact lenses for the control of myopia, there have been no reports of the use of gas permeable contact lenses for this purpose. In the study reported here, 100 myopic children between the ages of 8 and 13 years were fitted with Paraperm O2 plus silicone-acrylate contact lenses to be worn for a period of 3 years. Lenses were fitted by the alignment method, most lenses having diameters from 8.5 to 9.0 mm. At the end of 2 years 60 subjects remained in the study, 53 of whom were wearing their lenses on a regular basis and the other 7 were irregular wearers. Mean increases in myopia during the 2-year period were found to be 0.28 D for the subjects who wore their lenses regularly and 0.93 D for the irregular wearers, compared to 0.80 D for a group of 31 age-matched single vision spectacle lens wearers. Mean corneal refracting power was found to decrease (the cornea flattened) 0.33 D for the regular wearers as compared to an increase of 0.14 D for the irregular wearers and a decrease of 0.13 D for the spectacle wearers. Mean changes in axial length were an increase of 0.1 mm for the regular wearers, an increase of 0.4 mm for the irregular wearers, and an increase of 0.6 mm for the spectacle wearers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2927912 TI - Validation of a method for measuring small color differences in pigmented contact lenses. AB - A method for measuring and quantifying color variability of soft contact lenses is presented in this paper. The lenses studied are opaquely pigmented, varying in color intensity in each of four hues. The instrument selected for color measurement is the HunterLab ColorQUEST reflectance spectrophotometer using integrating sphere geometry and a customized contact lens support. Total color difference is measured using the Commission International de l'Eclairage (CIE), 1976 L* a* b* color space in delta-E* units. The correlation between the instrumental measurement and human estimation of color intensity difference is presented graphically for each hue. Trained inspectors ranked the eight lenses per hue from lightest to darkest on a linear scale which was converted to the instrumental delta-E* units. The instrument validation is based upon (1) maximum average differences of less than 1.1 delta-E* between the instrument and inspectors, and (2) overall repeatability (SD) of +/- 0.1 for the instrument vs. +/- 0.3 for the inspectors. PMID- 2927913 TI - Optometric services in the prison system. AB - Traditionally, optometric services have been limited to practitioners' offices or clinical settings. Recently more optometric practitioners have ventured out of the office to provide eye care to those who otherwise would not receive such care. This report discusses the need to provide eye care to prison inmates. It also addresses the nature of vision and eye problems more common among the prison population and the need for mandated eye care for the inmates. PMID- 2927914 TI - Mental concentration and the pattern reversal visual evoked response. AB - The pattern reversal visually evoked response (VER) was recorded using a small check size stimulus. Subjects viewed the VER stimulus with the left eye and a light emitting diode (LED) with the right eye. They were asked to concentrate on either the VER stimulus or the LED. The two targets were arranged so that the left eye remained accurately focused on, and directed to, the center of the VER stimulus throughout the recordings. The VER wave became attenuated when the subject concentrated on the LED. The wave was reduced to around two-thirds of the amplitude present when concentrating on the VER stimulus. PMID- 2927915 TI - Delivery of optometric care in nontraditional settings: the long-term care facility. AB - The changing demographics of our population dictate that in the future optometrists will care for increasing numbers of older patients. Significant numbers of these elders will reside in long-term care facilities. Optometry curricula have begun to respond to this need by training students currently enrolled in colleges of optometry to provide eye care in the nursing home setting. PMID- 2927916 TI - An alternative for the correction of the Class II low mandibular plane angle. AB - The traditional orthodontic and/or orthognathic surgical management of the Class II deep-bite case with a low mandibular plane angle has often been difficult; optimal esthetic results have not always been achieved, and long-term stability was often unpredictable. Many of these patients may benefit functionally and esthetically from appropriate orthodontic treatment and double-jaw surgical intervention to reorient the occlusal plane toward normal (8 degrees +/- 5 degrees to Frankfort horizontal) by moving the posterior maxilla and mandible superiorly and correcting into a Class I skeletal and occlusal relationship. As the occlusal plane angulation is increased, the upper incisor angulation decreases, the lower incisor angulation increases, the chin rotates down and backward relative to the lower incisor occlusal plane tips, and the mandibular plane angle increases. The principle of changing the occlusal plane has provided a means to improve the functional and esthetic results for the correction of this type of facial deformity, as well as many others. PMID- 2927917 TI - Treatment of an oral erythroplastic squamous cell carcinoma with Mohs' micrographic surgery. AB - In the case presented in this article, a large superficial erythroplastic oral carcinoma with vaguely delineated clinical borders and foci of invasive squamous cell carcinoma was treated with Mohs' micrographic surgery. This provided a safe, thorough, yet conservative mode of treatment. Mohs' micrographic surgery may be considered among the alternative treatments for selected mucosal lesions of squamous cell carcinoma. PMID- 2927918 TI - A comparative study of normal sensibility of the inferior alveolar nerve and the infraorbital nerve. AB - In order to assess the degree of similarity of the infraorbital nerve and inferior alveolar nerve, thirty subjects with no history of sensory injury were examined by a battery of neurosensory tests including: light touch, brush stroke direction, two-point discrimination, and thermal disk temperature assessment. In a matched sample experimental design, the sensibility of the inferior alveolar nerve (lower lip) was compared to the inferior orbital nerve (upper lip). The product moment correlations revealed a significant relationship (degree of sameness) between the upper and lower lip. The comparison of the upper and lower lip appear to be acceptable for retrospective tests for detection of neurosensory injury of the inferior alveolar nerve. Of these tests, light touch appears to be the most consistent while remaining sensitive to individual variation. The thermal disk assessment was least sensitive in that no individual variation could be demonstrated. In addition, there appear to be greater variations in men than in women. PMID- 2927919 TI - Intraoral infection with Mycobacterium chelonae. A case report. AB - An 8-year-old girl had a visibly enlarged submandibular lymph node and a reddish, spongy swelling of the gingiva in the upper right canine region. Culturing of the gingival tissue resulted in the isolation of Mycobacterium chelonae, and the patient showed a specific skin hypersensitivity reaction to M. chelonae sensitin. The gingival swelling disappeared spontaneously without scarring within 5 weeks after the biopsy. There was no recurrence intraorally during the 2 1/2-year follow-up, the generalized lymphadenopathy subsided within 2 years, and at the last visit, the submandibular lymph node could barely be felt. The patient received no medication during the course of the disease. A tortoise held as a pet by the girl could possibly have been the source of infection since iatrogenic sources of infection could be excluded. PMID- 2927920 TI - Nasotracheal tube obstruction from a central incisor. Report of a case. AB - After maxillofacial trauma, teeth and other objects can become potential foreign bodies. Whenever possible, careful examination before intubation should be undertaken to avoid serious morbidity secondary to aspiration. The anesthesiologist should be informed and necessary preventive measures taken. This article describes a situation in which this not being done could potentially have led to serious complications. PMID- 2927921 TI - Treatment of muscle spasms with oral dantrolene sodium. AB - A case of severe muscle spasms relieved by oral administration of dantrolene sodium is presented. The patient had undergone full-mouth extraction 2 days prior to onset of her spasms. The treatment consisted of intravenous diazepam followed by oral dantrolene sodium. The spasms lasted for approximately 10 days. PMID- 2927922 TI - Recognition and management of invasive pharyngeal candidiasis in acute leukemia. AB - Invasive fungal infection is a potentially fatal complication in severely neutropenic patients with acute leukemia. Two cases are presented to demonstrate specific clinical signs and symptoms that should alert the clinician to the possibility of aggressive invasive candidiasis of the oropharynx. PMID- 2927923 TI - Intraoral application of microcolpohysteroscopy. A new technique for clinical examination of oral tissues at high magnification. AB - Colposcopy is an established technique for diagnosis in gynecology. A recently developed optical instrument is the contact microcolpohysteroscope for macroscopic examination of the cervical mucosa. This article evaluates the application of the contact microcolpohysteroscope for examination and recording of the surface topography of the hard and soft tissues of the oral cavity. This is a promising, noninvasive method of observation of tissue surfaces at high magnification. Modifications of the method for oral use are described, and potential applications for diagnosis and research in dentistry are proposed. PMID- 2927924 TI - Salivary and microbial conditions and dental health in patients with Crohn's disease: a 3-year study. AB - Salivary and microbial conditions and dental status were examined in 21 patients randomly selected from a group of patients with Crohn's disease. Three years later, the patients were recalled and the same factors were reexamined. The results showed that the caries experience in these patients was higher than that observed in age-matched subjects in a normal reference population. Dietary examination disclosed no changes in intake frequencies of different common food items during the 3-year period. All patients had a normal saliva flow rate and buffer capacity. Protein concentration tended to increase and sialic acid to decrease when compared with available reference data. The number of salivary mutans streptococci organisms and lactobacilli was high both at baseline and after 3 years, and no significant differences were observed between the two examinations. Patients with Crohn's disease belong to a high-risk group in relation to caries and should be given comprehensive preventive caries measures. PMID- 2927925 TI - Oral hyperpigmentation in HIV-infected patients. AB - Six cases of oral hyperpigmentation in HIV-infected patients are reported. While in two patients the lesions could be related to systemic clofazimine or ketoconazole therapy, in the other patients the cause remained unknown. Clinically, the pigmentations were characterized by a sudden onset and the appearance of well-defined, brown-black macules in the buccal mucosa, the gingiva, the hard palate, or the lateral borders of the tongue. In one patient, longitudinal hyperpigmented striae were observed on all fingernails and toenails. Histologically, hyperpigmentations associated with systemic medication revealed accumulation of melanin in phagocytes and extracellularly within the connective tissue. In those lesions with unknown cause, melanin was restricted to keratinocytes of the basal cell layer or to extracellular foci in the lamina propria. The clinical and histologic findings, as well as differential diagnosis, are discussed. PMID- 2927927 TI - Acquired immune deficiency syndrome presenting as a palatal perforation. AB - Head and neck manifestations are particularly frequent in the acquired immune deficiency syndrome. An unusual case of acquired immune deficiency syndrome in a female prostitute whose initial presentation included a palatal perforation is reported. This case is also noteworthy because the patient died of disseminated miliary tuberculosis, a disease only recently included in the Centers for Disease Control case definition of AIDS. PMID- 2927926 TI - Kaposi's sarcoma of the parotid gland in acquired immunodeficiency syndrome. AB - A patient with acquired immunodeficiency syndrome complained of a dry mouth and bilateral swelling of the parotid glands. Kaposi's sarcoma (KS) was found within the tissue of the parotid gland. Although KS is a common manifestation of acquired immunodeficiency syndrome, the presence of KS in the salivary glands is very rare. The human immunodeficiency virus I (HIV-I) genome was not identified in parotid glandular cells or in KS cells in this case, although the virus was detected in infiltrating lymphocytes and in tissue macrophages. PMID- 2927928 TI - Immune deficiency with polymorphic reticulosis. AB - A case of fatal polymorphic reticulosis, currently considered to be a peripheral T cell lymphoma, that was initially seen as a nasolabial swelling with a left lower lobe pulmonary nodule in a 40-year-old woman is reported. At autopsy, it was found to be associated with disseminated cryptococcosis and Pneumocystis carinii pneumonia associated with secondary severe immunodeficiency of unknown origin. PMID- 2927929 TI - The usefulness of dye-penetration studies reexamined. AB - An in vitro study to determine the usefulness of dye-penetration studies was conducted. In part I, teeth were prepared through the foramen and then left open, either apically, coronally, or at both ends. In all cases, the dye did not penetrate the full length of the canal. The only exception was when both ends were left open and the teeth were placed into the dye in an upright position. In part II, a measurable defect in a canal filling the length of the canal was created and left open apically. When the tooth was immersed in dye, the penetration was incomplete. When the air was removed by vacuum pump prior to placement in the dye, the penetration was total. The validity of dye studies that do not consider entrapped air is open to question. PMID- 2927930 TI - A 25% tannic acid solution as a root canal irrigant cleanser: a scanning electron microscope study. AB - A scanning electron microscope was used to evaluate the cleansing properties of a 25% tannic acid solution on the dentinal surface in the pulp chamber of endodontically prepared teeth. This was compared with the amorphous smear layer of the canal with the use of hydrogen peroxide and sodium hypochlorite solution as an irrigant. The tannic acid solution removed the smear layer more effectively than the regular cleansing agent. PMID- 2927931 TI - Dental radiography exposure of the Hiroshima and Nagasaki populations. AB - Dental radiography doses in Hiroshima and Nagasaki were estimated on the basis of survey data from dental hospitals and clinics in Hiroshima and Nagasaki, and doses were measured by thermoluminescent dosimeters and a phantom. Doses to organs, including the lens, pituitary fossa, thyroid gland, and skin were calculated from data obtained during a 2-week survey in both cities. The mean caput doses were calculated from the data indicating frequency per year and were tabulated by organs, age, teeth examined, type of examination, population, sex, and city. No significant difference was observed by age, population, sex, or city. Currently the doses incurred during dental radiography may not be sufficiently high to cause bias in the assessments for late radiation effects among atomic-bomb survivors. However, the mean caput thyroid doses of 62 mrad and 67 mrad in Hiroshima and Nagasaki, respectively, cannot be ignored from the standpoint of their potential in contributing to radiation-induced carcinogenesis. PMID- 2927932 TI - Facial phleboliths. PMID- 2927933 TI - Dystrophic calcification of the submandibular gland. PMID- 2927934 TI - Technique error mimics impaction. PMID- 2927935 TI - [Clinical observations in mixed connective tissue disease]. AB - The authors report their observations gathered by follow-up studies of many years duration on 67 patients suffering from mixed connective tissue disease. The period preceding the overt disease, its duration and its characteristic symptoms were examined. Concerning the severity of the clinical course, the authors distinguished between a less and a more severe form of the disease. Organ specific manifestations occurring in the two types of the disorder, the number of active phases per year, therapeutic tools and the prognosis were analysed. The authors assume that the more severe form of the disease may have some traits resembling those of systemic lupus erythematosus, but in the meantime, in the less severe type of the disease some features shared by rheumatic disorders can be found. PMID- 2927936 TI - [Determination of the degree of saturation of calcium hydrogen phosphate in the urine]. AB - Calcium-hydrogen-phosphate (CaHPO4) was considered as one of the main factors governing renal calculus formation. The degree of saturation (expressed as activity product) with respect to this phase was therefore calculated in urines of 36 hypercalciuric children (20 absorptive, 16 renal subtype) with isolated hematuria, 10 renal stone patients, and 30 healthy controls. On low calcium diet 12 children of the absorptive hypercalciuric-, 13 of the renal hypercalciuric and 7 of the renal stone forming children hat their urines in the saturated zone - irrespective of the evolution of hypercalciuria Ca/cr ratio. Thiazide normalised the activity product in all groups. The use of the Ca/cr ratio as the sole parameter in the investigation of children with isolated hematuria and hypercalciuria or calcium nephrolithiasis is therefore insufficient, simultaneous determinations of the state of saturation of urines is recommended. This technique should also allow a quantitative assessment of the various therapeutic regimens recommended. PMID- 2927937 TI - [Intrauterine insemination with "washed" sperm]. AB - The authors have been performing intrauterine insemination with the washed sperm of the husband since 1986. Previous to the intervention husband and wife went through a very thorough infertility examination according to the principles of the WHO. The cycle of women given intrauterine insemination was monitored. The maximum value of estradiol was measured on the 12th and 13th day of the cycle and the maximum mean value of the follicles on the 13th-14th day. In cases of ovulation the mean value of serum progesterone was found to rise on the 14th-15th day of the cycle. The semen was washed and concentrated, different protein components and bacteria were eliminated and the fraction with good motility was used for insemination. Intrauterine insemination with washed human sperm was carried out with 2 groups of patients. In the series studied the authors induced with intrauterine insemination 24 pregnancies in 100 infertile marriages. Intrauterine insemination was found to be successful if the infertility was caused by the hostility or poor quality of the cervix mucus. The treatment may be successful also in cases with slighter alteration of the spermiogram, whereas no results can be expected from intrauterine insemination with spermiograms displaying more serious alteration. PMID- 2927938 TI - [Incidence over 10% of premature deliveries in Hungary (based on the experience in Borsod-Abauj-Zempln County)]. AB - The incidence over 10% of premature delivery in Hungary was studied. The cause which motivated this work was the fact that despite of several preventive and therapeutic measures the incidence e.g. in BAZ county surpassed even the average of the country. Professors of clinics in different countries of Europe as well as medical societies dealing with this question have been consulted about the matter of whether it was sufficient to consider a neonate a premature infant and the delivery a premature one solely on the basis of birth weight (under 2.500 g). Data of BAZ county proved that this determination was misleading and proposals are made concerning the modification on the basis of the examinations of the authors. PMID- 2927939 TI - [Symptomless (silent) myocardial ischemia and its prognostic significance]. AB - The authors studied the prognostic significance of Silent myocardial ischemia. To study the correlation between the silent ischemia before the operation of coronary revascularization and the perioperative complications (infarction, mortality) Holter-monitoring (HM) was performed with 26 patients. The average time of HM was 43 +/- 3.1 h. During the observation period total 138 silent ischemic episodes were registered with 7 patients. The average heart rate observed during the ischemic event did not differ from that observed in other periods. Three myocardial infarctions occurred in the perioperative period one of them was of lethal outcome. Silent ischemia was detected in 2 of 3 patients before operation. The patient who displayed the gravest ischemic alteration died of perioperative myocardial infarction. On the basis of their observations the authors attribute prognostic significance to the preoperative silent myocardial ischemia. PMID- 2927940 TI - [An intrauterine device used to enhance the concentration of radiation therapy]. AB - The author discusses about non-usual application of Cu containing intrauterine contraceptive device. An oophoropexy was performed on a 19 years old female suffering from Hodgkin disease. A Cu intrauterine contraceptive device was introduced into the uterine cavity to help in localising the radiological treatment. The author did not find any report pertaining to this topic in the literature. PMID- 2927941 TI - [Reality orientation training: a method of group therapy of patients with dementia. Problems and possibilities of evaluating the effect of treatment of patients with various forms of dementia]. AB - Authors describe a method called reality orientation training, a possibility of group treatment for patients suffering from dementia. They summarize the main statements of the literature and give account of their own battery for diagnostic classification and treatment. They outline the practical difficulties in the measurement of the effectivity of the treatment employed in demented patients. PMID- 2927942 TI - [Special education as hygiene nurse. A contribution to health care]. PMID- 2927943 TI - [Dialog between nurse and patient]. PMID- 2927944 TI - Amplified DNA in cells of genetic melanoma of Xiphophorus. AB - Melanomas of genetic origin develop in interspecies hybrids of the fish Xiphophorus. Cytogenetic analyses have indicated chromosomal manifestations of amplified DNA in cells of an in vitro established cell line derived from a melanoma. We have employed strategies of differential hybridization in agarose gels to isolate and clone a portion of the amplified DNA. Amplification was about 20-fold in melanoma cells established in culture and about 10-fold in 2 out of 5 melanomas directly derived from the animal. The amplified DNA contained at least one transcription unit that is evolutionarily conserved in all vertebrates tested, including chicken, murines and man. Our results indicate that amplification of an as yet uncharacterized gene is involved in genetic melanoma of Xiphophorus. PMID- 2927945 TI - Generation of new oncogenic murine retroviruses by cotransfection of cloned AKR and MH2 proviruses. AB - We have obtained a set of oncogenic recombinant retroviruses, the 3RV complex, by cotransfecting murine fibroblasts (SC-1 cells) with plasmids containing the cloned genomes of the avian MH2 and murine AKR viruses. The transfected culture (TAM-2) was shown to release murine transforming viruses by means of reverse transcription and focus formation assays. Analysis of TAM-2 intracellular RNA revealed new transcripts hybridizing with the oncogenes myc and mil and cross hybridizing with an AKR probe. The biological activity of the 3RV complex was tested for the induction of murine macrophage proliferation in the absence of exogenous growth factors, a property described as the result of mil and myc cooperativity. Cell-free supernatants from 3RV transformed fibroblasts were indeed able to induce the proliferation of macrophage-like cells from murine bone marrow and spleen primary cultures. Such cultures were capable of continuous growth and showed independence from exogenous myeloid growth factors. The cells expressed antigenic markers and functional properties specific of the monocytic macrophage lineage. These results suggest that transfection-induced recombination could be a novel way to generate biologically active recombinant retroviruses. PMID- 2927946 TI - A novel mechanism for covalent attachment of fatty acid to SV40 large T antigen. AB - The plasma membrane associated subclass of simian virus 40 large T antigen is specifically acylated with palmitic acid in vivo. To further analyze possible biological functions of fatty acid acylation, we developed a target-bound cell free in vitro acylation assay, in which immunopurified large T, bound to protein A-sepharose, was incubated with [3H]fatty acid. In this assay, large T was efficiently labeled with [3H]palmitic acid, but not with [3H]myristic acid. Thus the specificity of the in vivo labeling was preserved in vitro, too. The specific acylation of large T in vitro seemed to occur by an autocatalytic reaction, since it was found to be independent of added acyltransferases and exogenous energy. The energy for this reaction must be provided by the large T molecule itself, probably by an energy-rich internal ester bond. Our results provide evidence for a novel mechanism for the covalent attachment of fatty acids to proteins, which might also operate in vivo. PMID- 2927947 TI - Predisposition to retinoblastoma due to a translocation within the 4.7R locus. AB - A candidate for the retinoblastoma (Rb) predisposition gene, known as 4.7R, has recently been cloned. Authentication of this gene depends on abnormalities detected in either the genomic sequence or transcription products (or both) in Rb tumours and cell lines. We report a constitutional chromosome translocation, with a breakpoint lying within the putative retinoblastoma gene, from a patient with retinoblastoma; there is an associated small intragenic deletion. This structural rearrangement, which confers susceptibility to tumour formation, provides strong evidence that the 4.7R cDNA represents the Rb gene. PMID- 2927948 TI - Activation of the trk oncogene by alternatively spliced muscle and non-muscle tropomyosin sequences. AB - We have constructed a derivative of the trk oncogene in which the cytoskeletal tropomyosin sequences are replaced with skeletal muscle alpha-tropomyosin sequences derived from the same tropomyosin gene by alternative splicing. The biochemical and biological properties of this derivative are indistinguishable from those of the naturally occurring trk oncogene. Thus activation of the oncogenic activity of trk is a function of structural features of tropomyosin which are common to both skeletal muscle and non-muscle isoforms. PMID- 2927949 TI - Legal significance of living wills. PMID- 2927950 TI - Electronic information: a new dimension. PMID- 2927951 TI - Lessons from the Navajo. PMID- 2927952 TI - Days of miracle and wonder. PMID- 2927953 TI - False negative cervical cytology. PMID- 2927955 TI - Area nurse examines International Nurses' Day in Yugoslavia. PMID- 2927954 TI - The impact of one federal regulation on nursing practice in a home health agency. PMID- 2927956 TI - An antigen detection enzyme immunoassay for the diagnosis of rhodesiense sleeping sickness. AB - A monoclonal antibody raised against a non-variable surface antigen of Trypanosoma brucei rhodesiense procyclic trypomastigotes was used to develop an antigen detection enzyme immunoassay for the diagnosis of rhodesiense sleeping sickness. The assay was evaluated using 211 sera from clinically suspected cases: 142 from parasitologically proven cases and 69 from patients who were negative on parasitological examination. The test was positive in 128 out of 142 parasitologically proven cases. The negative cases may have been in the early stages of the disease, or may represent patients with antibody levels sufficient to prevent detection of antigen. Of particular significance, however, was the finding that eight of the 69 patients with undiagnosed disease were antigen positive despite the negative parasitological findings. Since false-positive reactions were not observed with blood donor sera, or with sera from malaria, schistosomiasis and leishmaniasis patients, it is reasonable to conclude that the eight antigen-positive patients were actual cases of sleeping sickness. The remaining 61 cases who were negative for both parasitaemia and antigenaemia may conceivably represent the variety of diseases whose clinical manifestations resemble those of rhodesiense sleeping sickness. The antigen detection method would thus not only be complementary to parasitological diagnosis, but essential for correct diagnosis in certain stages of the disease. PMID- 2927957 TI - Genetic variation in the humoral immune responses of mice to the nematode Trichuris muris. AB - Genetically based differences in the antibody responses to the large intestinal nematode Trichuris muris were studied in two groups of H-2 congenic strains of mice that differed in their relative resistance to infection with this parasite. The primary antibody response to parasite excretory/secretory (E/S) antigen was predominantly an IgG response with the strains forming two distinct groups, defined by their genetic background. The more susceptible B10 genetic background mice had strikingly higher antibody levels than mice of the BALB genetic background. Superimposed upon these background effects were clearly defined influences attributable to H-2-linked genes, strains which differed genetically only at H-2 loci exhibiting differences in the kinetics of the antibody response. Only B10.G and B10.BR mice showed any great increase in IgM levels post infection. No IgA specific to E/S antigen was detected in the peripheral circulation of any strain at any time post-infection. Antibody responses to a 40 43 kD antigen revealed clear H-2-linked gene effects, with mice sharing the H-2k haplotype (B10.BR, BALB/K) exhibiting considerably higher total antibody levels than strains expressing other haplotypes; mice of the H-2d haplotype (BALB/c, B10.D2/n) responded very weakly to this antigen. A Western blot analysis of antigen recognition by antibody revealed similarities between the mouse strains in their total antibody responses to T. muris E/S antigen. However, immunoprecipitation studies showed that in general the more susceptible B10 congenic strains had wider spectra of antigen recognition than the BALB congenics. Strains sharing the same H-2 haplotype had dissimilar antigen recognition profiles, but strains sharing the H-2b haplotype (B10, BALB/B) recognized a low mol. wt antigen (20-23 kD) not recognized by any other strain, suggesting an exclusively H-2b restriction in the recognition of this antigen. These results support the conclusion that both H-2-linked and background genes play important roles in controlling the humoral immune response to T. muris infection. PMID- 2927958 TI - Resection arthroplasty for comminuted olecranon fractures. AB - Five cases of comminuted olecranon fractures treated by resection of the proximal fragments are reviewed. The patients' average age was 56 years and all were radiographically osteopenic. The triceps was advanced and attached to the distal olecranon with the elbow flexed at 90 degrees. A standard postoperative regimen was used with immobilization for three weeks in plaster at 45 to 60 degrees of flexion followed by progression to cautious active range of motion exercises. Follow-up of from 18 to 54 months shows an average active range of motion of 10 degrees flexion to 120 degrees flexion. There were no complaints or clinical evidence of instability and minimal degenerative changes were seen on radiography. We conclude that resection arthroplasty of comminuted olecranon fractures yields excellent clinical and functional results in elderly patients. PMID- 2927960 TI - Intramedullary fixation of unstable distal radius fractures. A method of fixation allowing early motion. AB - During a four-year period, we have treated unstable fractures of the distal radius with closed anatomic reduction and insertion of a Rush intramedullary rod through a small dorsoradial wrist incision, followed by early controlled range of motion. In an attempt to reduce the stiffness commonly seen in the fingers, wrist, and elbow, a simple method of more stable fixation and early motion was instituted. Patient assessment using common anatomic and functional classification systems revealed good to excellent results in 35 of 36 patients (98%). Only three patients had complications, and these were all minor in nature. Three rods were removed, all because of prominence and irritation of the tip of the rod over the radial styloid. The procedure is technically reproducible, and has a very high rate of patient acceptance and satisfaction. PMID- 2927959 TI - Total knee replacement in Paget's disease. AB - Due to rapid bone turnover in Paget's disease, loosening of artificial joints might be expected to be a problem, especially if they are of the tissue ingrowth type. Two patients with Paget's disease, who had had knee replacement with this type of prosthesis and have been followed for two years, have both done well to date. It appears that ingrowth-type implants can be used in the presence of Paget's disease. Paget's disease, which was first described in 1877, is characterized by a rapid turnover of bone. The cause of Paget's disease has yet to be determined. The common sites attacked, at least in a Canadian population, are the pelvis (45.4%), vertebrae (22%), femur (10%), tibiae (3.6%), and patellae (0.2%). Paget's occasionally gives rise to arthritic changes in a joint adjacent to the lesion, although the precise mechanism is uncertain. Disturbance of the subchondral bone due to hyperemia and overload due to increasing deformity have been cited as possible reasons. There was and is concern that joint replacement with cemented components would result in rapid loosening due to increased bone turnover. However, it has yet to prove a major problem. So far no reports have appeared in the literature on the effects of Paget's disease on knee replacement, specifically the effects of the porous tissue ingrowth type components that are now in common use. Two patients with Paget's disease around the knee who had had a knee replacement of this type are presented, with over two years of follow-up. PMID- 2927961 TI - Team physician #5. Salter-Harris type I fracture of the distal radius due to weightlifting. AB - A Salter-Harris Type I distal radius fracture was sustained by a skeletally immature adolescent while performing a supine bench press during weight training. Closed reduction was accomplished without difficulty. Fractures in adolescence due to weightlifting are rare but illustrate the need for proper instruction and supervision. PMID- 2927962 TI - Imaging rounds #98. Ewing's sarcoma with pathologic fracture. PMID- 2927963 TI - The Heffington frame. PMID- 2927964 TI - Neuropathic ankle in CMT disease. PMID- 2927966 TI - Seizure disorders. PMID- 2927965 TI - Common psychiatric problems and the pediatrician. PMID- 2927967 TI - Mechanics and energetics of breathing in newly diagnosed infants with cystic fibrosis: effect of combined bronchodilator and chest physical therapy. AB - Response to bronchodilator (BD) and chest physical therapy (CPT) was evaluated in newly diagnosed infants with cystic fibrosis (n = 13; age, 6.9 +/- 1.5 SE months) who were asymptomatic for lung disease at the time of the study. Lung function was assessed from the mechanics and energetics of breathing prior to and following combined BD and CPT. After therapy, respiratory rate, tidal volume, minute ventilation, and pulmonary compliance were not statistically different from values under baseline conditions. In contrast, there was a significant decrease in pulmonary resistance (-34%; P less than 0.05) and the resistive work of breathing (-26%; P less than 0.05) following the combined treatment. The effect of combined BD and CPT in decreasing the resistive respiratory load may be related to relief of subclinical bronchospasm, reduction in mucosal edema, and mobilization of mucous secretions. PMID- 2927968 TI - Prenatal relationship of surfactant lipid and protein constituents in infants with respiratory distress syndrome: a preliminary communication. AB - The prenatal relationships between surfactant disaturated phosphatidylcholine (DSPC) and surfactant-associated proteins of preterm infants with respiratory distress syndrome (RDS) have not been well documented. In the present study we measured the concentration of DSPC, surfactant glycoproteins (GP), and surfactant proteolipids (PLP) in amniotic fluids obtained within 6 hours prior to delivery of 16 newborn infants with gestational ages between 27 and 32 weeks. In control infants of 27-32 weeks gestation without RDS, the values of DSPC, GP, and PLP per milliliter of amniotic fluid were 20 +/- 2.9 micrograms, 684 +/- 115.3 ng and 289 +/- 62.5 ng, respectively. These values were significantly higher, threefold for PLP, fourfold for DSPC, and fivefold for GP, than amniotic fluid levels in infants with RDS. The findings support the concept that immaturity of surfactant in RDS involves both phospholipids and surfactant-associated proteins. Measurements of surfactant lipid-protein complex appear to enhance the reliability for identifying prenatally, infants at risk of developing hyaline membrane disease. More extensive studies are warranted to assess the usefulness of these assays for clinical application. PMID- 2927970 TI - A correction formula for computing specific airway resistance from a single-step measurement. AB - Specific airway resistance (SRaw) is conventionally determined by multiplying the plethysmographically measured values of airway resistance and functional residual capacity (FRC). An alternative single-step method, which avoids the need for airway occlusion during determination of FRC, has been described by Dab and Alexander. The single-step method provides no correction for resistance or dead space of the apparatus and, as a result, systematically overestimates SRaw. Using 1,000 paired measurements, it was possible to compute a formula for correcting the single-step measurement. This correction formula can be adjusted and applied to measurements made in any laboratory. The unlimited applicability of the proposed correction has been demonstrated by 234 plethysmographic measurements made in the Pediatric Clinic in Rome. PMID- 2927969 TI - The reproducibility and agreement of three indices of airway responsiveness to histamine in asthmatic children. AB - In 12 asthmatic children, aged 8-14 years, we investigated the possibility of using a provocation concentration of histamine (PC) causing a 10% or 15% fall in baseline forced expiratory volume in 1 sec (FEV1), instead of a PC20 histamine, in the assessment of bronchial hyperreactivity. Inhalation challenge tests were performed on days 6 and 7 after withdrawal of medication. PC10, PC15, and PC20 were calculated from the dose-response curves. Reproducibilities for PC10, PC15, and PC20 values for both days, determined by Student's t-test, were not significantly different. Correlation coefficients between PC20 and PC15 values on days 6 and 7 and between PC10 values on days 6 and 7 were 0.82 and 0.76, respectively; between PC20 values on day 6 and PC15 values on day 7; and between PC20 values on day 6 and PC10 values on day 7 they were 0.84 and 0.82, respectively. (P less than 0.01 for all r values). The predictive value of PC20 for PC10 and PC15 was determined by a least-squares regression line with 95% confidence intervals. Variances between PC10, PC15, and PC20 were not significantly different on either day 6 or 7. Our data show that a PC10, as well as a PC15, can be used in the assessment of the degree of bronchial hyperreactivity in children with asthma. PMID- 2927971 TI - Effect of chest wall oscillation on mucus clearance: comparison of two vibrators. AB - This study was designed to investigate the effect of an experimental low-energy chest wall oscillator and of a commercial chest percussor on central airway mucociliary clearance. Five normal dogs were anesthetized, intubated, and placed supine in a trough to which the oscillator or percussor was mounted. Tracheal mucus velocity (TMV) was measured by radiopaque particle or charcoal spot movement. The commercial percussor (a fixed sinusoidal device) used at its minimum frequency of 40 Hz, produced a mean (+/- SE) maximum expiratory flow rate of 0.25 +/- 0.04 L/sec at the airway opening, and had no measurable effect on TMV. The experimental oscillator, when operated at a level sufficient to generate flows of 2-3 L/sec, and with an unbiased 13-Hz sine wave (estimated energy, 150 W), increased mean TMV to 204 +/- 13% of control (P less than 0.003); the percent increase was independent of baseline TMV. We conclude that moderate oscillatory power applied to the chest wall can enhance mucus clearance in central airways, but that currently available commercial percussors may not meet the mechanical requirements for this effect. PMID- 2927972 TI - Estimation of maximum expiratory flow-volume variables in children. AB - Different protocols for pulmonary function testing were evaluated in 611 children, 6-9 years old. Attention was paid to the necessary minimum number of acceptable maneuvers, the necessary maximum number of attempts, and the best of seven different methods for summarizing variables from maximum expiratory flow volume (MEFV) curves. The results of the study indicate that it is not useful to continue pulmonary function testing after eight attempts. The differences between the results from three or five acceptable maneuvers are not substantial for any method; in children, obtaining three acceptable curves seems sufficient. When flow variables are selected from one acceptable curve, as in the American Thoracic Society (ATS) guidelines, the reproducibility is somewhat less good than in methods in which results of various curves are averaged or selection is made from different curves. The method that has been recommended by the European Community for Coal and Steel for the selection of MEFV variables in teenagers and adults in Europe, was also demonstrated to be suitable for younger children. PMID- 2927973 TI - Sarcoidosis in children: personal observations on age distribution. PMID- 2927974 TI - Assessment of changes in 1-second forced expiratory volume in bronchial provocation testing. PMID- 2927975 TI - A computer-model analysis of the influence of the upper airway on passive flow volume loops in infants. AB - The present study was undertaken to determine the effects of upper airway resistance (Rua) and elastance (Eua) on the mechanical parameters calculated from the expiratory limb of the passive flow-volume curve in normal infants, using a computer model. The model included separate compartments for the respiratory system, upper airway, and measurement equipment. Inclusion of Rua in the model decreased the slope of the expiratory limb of the flow-volume loop, and the resistance calculated from the flow-volume loop accurately reflected the total resistance of the model. Inclusion of Eua in the model caused a decrease in the end-inspiratory (driving) pressure and a corresponding decrease in the peak expiratory flow but did not alter the slope of the linear portion of the expiratory limb of the flow-volume loop. Resistance calculated from the loop underestimated true model resistance by 14.5%. However, further small fluctuations in Eua did not cause significant variability in the value of resistance calculated. Total elastance was accurately calculated whether or not Rua and Eua were included in the model. The results of this analysis demonstrate that, while Eua causes the true resistance to be underestimated, fluctuations in Eua are not likely to be an important source of variability in the mechanical parameters calculated from the passive flow-volume loop; however, any changes in Rua will be reflected in the value of resistance calculated and therefore are likely to cause substantial variability in the calculated resistance. PMID- 2927977 TI - The American Pediatric Society and the Society for Pediatric Research. Abstracts and program outline. Washington, D.C., May 1-4, 1989. PMID- 2927976 TI - Increased bronchial responsiveness to histamine associated with shortened inhalation time. AB - A study was undertaken to assess the variability of results of histamine inhalation tests with the tidal breathing method, keeping the total dose of histamine delivered to the mouth constant but using either different nebulizers or the same Wright nebulizer operated under changing conditions. Seventeen asthmatic children had double histamine bronchial provocation tests with a Bennett-Twin nebulizer (output 0.31 ml/min, nebulization time 1 min) and a Wright nebulizer (output 0.15 ml/min, nebulization time 2 min), with a driving flow rate, in both instances, of 7 L/min. Another group of 15 asthmatic children had double provocation tests with a Wright nebulizer driven by a flow rate of either 7 L/min (output 0.15 ml/min, nebulization time 2 min) or 12 L/min (output 0.30 ml/min, nebulization time 1 min). In each experiment the volume of histamine solution delivered was about 0.30 ml. PC20-FEV1 was significantly lower, indicating an increased bronchial response, when both methods using "faster" delivery of histamine were used. We conclude that comparison of results obtained with histamine inhalation tests by the tidal breathing method cannot be made unless the nebulizer and operating criteria are the same. PMID- 2927978 TI - Proceedings of a workshop on vaccines for otitis media. Pittsburgh, PA, September 1-2, 1988. PMID- 2927979 TI - The role of antibodies to pneumococcal C polysaccharide in otitis media. PMID- 2927980 TI - Animal model for influenza A otitis media. PMID- 2927981 TI - Human adult immunogenicity of protein-coupled pneumococcal capsular antigens of serotypes prevalent in otitis media. PMID- 2927982 TI - A vaccine for otitis media: is there a need? What are the prospects? PMID- 2927983 TI - Epidemiology of otitis media. PMID- 2927984 TI - Routine chest radiographs in pediatric intensive care: a prospective study. AB - The clinical value of routine chest radiographs was prospectively evaluated in a pediatric intensive care unit. Physicians were asked to predict findings of clinical impact in 353 routine morning chest radiographs performed in 101 patients after examining the patients. In 81 instances (23%), the clinical impact of the chest radiographs was incorrectly predicted and significant alterations in management would have potentially been missed had the chest radiographs not been available. These 81 chest radiographs included 72 unpredicted radiographic changes of clinical significance, and nine chest radiographs in which a significant radiographic change was incorrectly predicted. Thirty five (43.2%) of these 81 chest radiographs had unpredicted pulmonary findings and 46 (56.8%) showed unpredicted appliance malpositions. Incorrect predictions were significantly associated with radiographs from patients who were younger, intubated, mechanically ventilated, and had indwelling central venous catheters. Level of training of the predicting physicians did not affect prediction accuracy. In analysis of 43 routine postintubation chest radiographs and 39 routine postcentral venous catheter placement chest radiographs, appliance malpositions were disclosed in 34.9% and 43.6%, respectively. Routine daily and post-appliance placement chest radiographs have significant clinical value in the pediatric intensive care unit. PMID- 2927985 TI - Otitis media in early childhood and cognitive, academic, and classroom performance of the school-aged child. AB - The relationship between the occurrence of otitis media during the first 3 years of life and cognitive, academic, and classroom performance during the third year of elementary school was evaluated in 44 socioeconomically disadvantaged children. The children attended a research day-care program where their otitis media experience and psychoeducational development were documented prospectively from birth. No significant relationship was found between otitis media in early childhood and performance on tests of verbal intelligence or academic achievement in the third year of school. The number of days of otitis media before 3 years of age was significantly correlated with teachers' ratings of children's attentional behavior in the classroom, however. Children with more early otitis media tended to be rated as less task oriented and less able to work independently than children with less otitis media. This was an exploratory study of a small number of children. Further study of the potential association is needed. PMID- 2927986 TI - Retinopathy of prematurity: a new epidemic? AB - This study provides the first empiric evidence for the existence of a new epidemic of retinopathy of prematurity-induced blindness. Data from a population based register of handicapping conditions in the Canadian province of British Columbia, and a birth weight-specific census of live-born infants in British Columbia, were used to determine annual, population-level incidences of retinopathy of prematurity-induced blindness during 1952 to 1983. Changes in incidence since the end of the original epidemic (1954) were determined by subdividing the 29-year period (1955 to 1983) into two intervals (1955 to 1964 and 1965 to 1983). Standardized incidence ratio analyses revealed a marginally significant increase in the overall incidence of retinopathy of prematurity induced blindness in the later as compared with the earlier period. Infants weighing 750 to 999 g at birth had a significantly increased standardized incidence ratio of 3.07 (95% confidence interval 1.26, 11.06). No increases in risk were observed in heavier or lighter weight infants. Because ascertainment and diagnostic changes do not explain the weight-specific increases in incidence, these results provide the first population-level evidence for a new epidemic. PMID- 2927987 TI - Reduction of mortality, morbidity, and respiratory distress syndrome in infants weighing less than 1,000 grams by treatment with betamethasone and ritodrine. AB - The efficacy of betamethasone has been questioned in infants of less than 28 week's gestation. From January 1983 to June 1986, 86 infants weighing 600 to 1,000 g were born at our center. Control of labor was attempted with ritodrine in all patients with less than or equal to 5 cm cervical dilation. If control were obtained, betamethasone was given 30 minutes later. Significant differences were found between the 33 infants born after 24 hours of betamethasone and those delivered before in terms of survival 90.1% v 56.6% (P = .001), respiratory distress syndrome 27.2% v 73.6% (P = .0001), and need for intermittent positive pressure ventilation 42.4% v 81.1% (P = .0005). The average hospital stay for beta-treated infants was 82 days v 99 days for nontreated infants. The average exposure to O2 after betamethasone was 12.7 days v 20.2 days, (P = .01), although need for intermittent positive pressure ventilation was similar (23 days) in the two groups. In infants who survived greater than 48 hours, the incidence of patent ductus arteriosus in the beta-group was 18.8% (6/32) v 44.4% (16/36) in the nontreated group (P = .04). Our data suggest that in infants weighing less than 1,000 g, control of labor with ritodrine for a minimum of 24 hours and administration of betamethasone can reduce significantly not only the incidence of respiratory distress syndrome but also mortality and morbidity. PMID- 2927988 TI - Neonatal neurodevelopmental examination as a predictor of neuromotor outcome in premature infants. AB - There was a marked correlation (P less than .000001) between neonatal neurodevelopmental examination results and neuromotor outcome at 1 year of age or older in 210 high-risk premature infants (mean birth weight 1,107 g, mean gestational age 28.4 weeks). This neonatal examination consisted of assessment of posture, extremity and axial tone, deep tendon reflexes, pathologic reflexes, primitive reflexes, symmetry, oromotor function, cranial nerve function, auditory and visual responses, and behavior. Premature infants whose neonatal neurodevelopmental examination results were abnormal had significantly higher incidences of both cerebral palsy (38% v 6%, P less than .000001) and minor neuromotor dysfunction (27% v 13%, p less than .05) than did premature infants whose examination results were normal. This correlation continued to be highly significant even with the analysis of subgroups (infants born at or before 27 weeks' gestation, infants with chronic lung disease discharged with oxygen supplementation, infants with periventricular hemorrhage) and when a variety of individual perinatal, demographic, and social variables were used as controls. Normal or nearly normal neonatal neurodevelopmental examination results can be used to reassure parents of high-risk premature infants. Although abnormal neonatal neurodevelopmental examination results cannot be used to diagnose handicap in premature infants, they can be used to select a group of high-risk infants who should be carefully monitored during infancy and childhood. PMID- 2927989 TI - Acute asthma: observations regarding the management of a pediatric emergency room. AB - Because inadequate assessment and inappropriate treatment of acute asthma have been implicated as contributing factors in morbidity and even deaths, the management of acute asthma, as practiced in an emergency room, were reviewed. The study population comprised 1,864 children (mean age 5.6 years; 65% boys) who attended the emergency room with acute asthma on 3,358 occasions during a 16 month period. Visits occurred more commonly in winter and usually in the evenings; 93% were self-referred and the mean duration of symptoms was 41 hours. Most acute episodes were associated with infection. Although chest auscultation, heart rate, and respiratory rate were recorded during the majority of visits, evidence that pulsus paradoxus had been measured could be found for only 1% of visits. Results of lung function and blood gas values were rarely recorded, but chest radiographs were obtained in 18% of visits. Drugs used in the emergency room included beta 2-agonists (93% of visits), theophylline (16%), and systemic steroids (4%), but no child received anticholinergic therapy. In 26% of patient visits, admission to hospital occurred; one patient died. The erratic fashion in which asthma severity appears to have been assessed and the failure to document whether lung function had been measured are causes for concern. The surprisingly high hospitalization rate may have been avoided if bronchodilators and corticosteroids had not been underused in the emergency room. PMID- 2927990 TI - High-versus low-dose, frequently administered, nebulized albuterol in children with severe, acute asthma. AB - Thirty-two 5- to 17-year-old children who had severe, acute asthma were randomly assigned to receive either high doses (0.15 mg/kg of body weight per dose) or low doses (0.05 mg/kg of body weight per dose) of nebulized albuterol every 20 minutes for six doses. Compared with the low-dose regimen, the high-dose regimen resulted in significantly greater improvement in forced expiratory volume in 1 second, forced vital capacity, and wheeze score and a lower hospitalization rate. The changes in heart rate, respiratory rate, blood pressure, white blood cell count, and serum potassium concentration did not differ significantly between the groups. The incidence of side effects, which included tremor, hyperactivity, and vomiting, was not significantly different in the two populations. Serum albuterol levels varied widely, but there was no correlation between the levels and the increase in heart rate or other side effects. high-dose, frequently administered, nebulized albuterol appears both safe and effective in treating severe, acute asthma in children. PMID- 2927991 TI - Demographic factors influencing the initiation of breast-feeding in an Israeli urban population. AB - The influence of demographic and prenatal factors on the initiation of breast feeding in an urban Israeli population was evaluated by interviewing 1,000 parturients prior to discharge from the hospital. The mothers were all Jewish, none were single, and none were social welfare dependents. Of these mothers, 72% were breast-feeding, 6% stated an intent to breast-feed, and 22% were formula feeding their infants. A significantly increased rate of breast-feeding was found among mothers with the following characteristics: those of orthodox religious belief, high educational level, in the academic and paraacademic professions, nonsmokers, those who worked outside of the home during the pregnancy, those who had previous breast-feeding success, and mothers whose husbands' attitude toward breast-feeding was positive. The decision to breast-feed was made prior to delivery in 85% of mothers. Participation of the mother and/or father in antenatal preparation courses did not significantly influence the initiation of breast-feeding. Multivariant analysis with a stepwise logistic regression model delineated the four factors most significantly associated with the initiation of breast-feeding: positive spousal attitude toward breast-feeding, orthodox religious belief, nonsmoking, and work outside of the home during the pregnancy. The expected probability for initiating breast-feeding was computed for the various combinations of these four categories and ranged from .94 with all factors present to .33 in the absence of these characteristics. Pediatrics 1989; 83:519-523; breast-feeding, Israel. PMID- 2927992 TI - Breast-feeding and the working mother: a profile. AB - Based on a survey of a nationally representative sample of new mothers, this study compares the incidence and duration of breast-feeding among mothers who were employed full-time outside the home with those not employed. Results indicated that the same proportion of mothers (55%) who were employed full-time as those not employed reported breast-feeding their infants in the hospital. Working full-time seemed to have a substantial impact on breast-feeding duration. Only 10% of full-time employed mothers breast-fed their infants at 6 months of age compared with 24% of those not employed. Analyses of breast-feeding by demographic characteristics indicated that in-hospital breast-feeding was relatively high among mothers who were not working outside the home and who were 30 years of age and older, in high family income groups, college educated, white, and living in the Mountain or Pacific region of the United States. Breast-feeding patterns among white and black mothers showed that a relatively high incidence of in-hospital breast-feeding was reported by black mothers who returned to work full time. Many more blacks than whites who were working full time were in those demographic subgroups that reported the highest incidence of breast-feeding: mothers who were 25 years of age and older, in high-income groups, and college educated. Ways to increase the level of breast-feeding among employed mothers are outlined. PMID- 2927994 TI - Heavy cocaine use by adolescents. AB - Adolescents are susceptible to becoming cocaine users. Twenty-eight teenagers in a drug rehabilitation program were identified as heavy cocaine users and questioned about their experiences. They reported family conflict leading to running away (86%), school drop-out (24%) and delinquent behaviors such as stealing (96%) and vandalism (57%). Cocaine use started at 14 years for 21%, with progression from onset to at least weekly use within eight weeks (54%). Side effects included sleep disturbance (18%) and tolerance to cocaine (25%). Withdrawal was characterized by cocaine craving up to one month later (93%). The majority (96%) were polydrug abusers. Possible causes of teen substance abuse are discussed, and the importance of prevention is emphasized. PMID- 2927993 TI - Zinc supplementation in infants with a nutritional pattern of failure to thrive: a double-blind, controlled study. AB - The objective of this study was to determine whether zinc deficiency is one of the factors involved in nutritional failure to thrive in infants and toddlers. Participants were selected on the basis of anthropometric criteria, particularly a decline in weight velocity preceding changes in length gains. The investigation was designed as a double-blind, randomized, pair-matched, controlled study of dietary zinc supplementation of 6 months' duration. Anthropometric data were collected at 0, 1, 3, and 6 months. Twenty-five pairs of infants completed the project. When compared with placebo-treated control children, the zinc supplemented group (combined sexes) and the supplemented boys showed significant improvements in standard deviation scores for weight for all three intervals, the largest differences occurring for the 0- to 3-month interval (P less than or equal to .0001). The zinc-supplemented girls demonstrated a trend toward improvements in changes in standard deviation scores for weight (P = .056). There were no differences in length gains for either boys or girls. This improvement in weight gains after zinc supplementation demonstrates that mild zinc deficiency can be one of the etiologic factors in nutritional failure to thrive during infancy. PMID- 2927995 TI - Fragile X syndrome: recognition in young children. AB - In recent years, a number of articles have appeared in the literature concerning the fragile X syndrome; however, in few cases was the diagnosis of the syndrome in young children discussed. A review of 20 children younger than 7 1/2 years of age who had the fragile X syndrome seen at the Cincinnati Center of Developmental Disorders was undertaken in an attempt to establish guidelines that would aid the practicing physician in determining which children should have a chromosomal analysis. All children were developmentally delayed; 95% had speech delays. Short attention span with hyperactivity, temper tantrums, mouthing of objects persisting at an age beyond when it would be expected, autistic behaviors, and poor gross motor coordination were seen in 50% or more of the children. Mental retardation was present in the family history of 65%, and 90% had a family history of at least one of the following: mental retardation, learning disabilities, or hyperactivity. The most common physical findings were long and/or wide and/or protruding ears, prominent jaw and/or long face, high arched palate, and a flattened nasal bridge. The fragile X syndrome can be recognized by noting key aspects of the behavioral and family histories as well as the physical findings. PMID- 2927996 TI - Prevalence of child sex rings. AB - Within a geographically defined population of 710,000, 31 child sex rings were identified by the police during a 2-year period. A total of 47 male perpetrators aged 16 to 82 years and 334 children aged 4 to 15 years were involved. The perpetrators usually operated alone or in pairs. Three rings were expanding and developing into semicommercial enterprises, however and four or more men participated in them. Children acting as ringleaders recruited victims for the perpetrator in 22 rings, usually in exchange for money. The offenses reported included fondling and masturbation (30 rings), oral, anal, or vaginal intercourse (21 rings), and production of child pornography (two rings). In addition, two adolescent prostitution rings involving 12- to 18-year-old boys were investigated by the police. During the 2-year period these sex rings accounted for 4.6% of all cases of child sexual abuse reported to the police and 6.6% of the subsequent prosecutions. PMID- 2927997 TI - Unsuspected infectious diseases and other medical diagnoses in the evaluation of internationally adopted children. AB - Seven simple screening tests--hepatitis B profile, urine culture for cytomegalovirus, Mantoux test for tuberculosis, stool examination for ova and parasites, VDRL, complete blood cell count, and vision and hearing screening- were used to evaluate 52 consecutive children at a pediatric clinic for international adoptees. In 63% of these children, unsuspected medical diagnoses were made by a combination of history, physical examination, and appropriate screening tests. When only those children previously examined by a physician in the United States were included in our analysis, the rate of unsuspected diagnosis remained high (67%). Omission of screening tests was the single most frequent cause of missed diagnoses, of which the majority were infectious diseases. More than 50% of our newly established diagnoses carried the potential for long-term sequelae without proper treatment. These data emphasize that internationally adopted children should receive a thorough screening evaluation for medical problems that may adversely affect their growth and development. PMID- 2927998 TI - Sexual maturity rating: a marker for effects of pubertal maturation on the adolescent electrocardiogram. AB - The heart is known to participate in the adolescent growth spurt. A peak increase in transverse diameter coincides with peak height velocity during pubertal maturation. The effects of maturation on the adolescent ECG were explored using sexual maturity rating (SMR) as a marker. ECGs were obtained from 751 patients 8 to 20 years of age seen for routine physical examinations. A total of 33 standard ECG measures were analyzed, with subjects separated by sex and SMR. Different trends were seen in boys and girls during the course of maturation for the majority of R and S wave amplitude measurements. Lower mean amplitudes were seen consistently in more mature (SMR 4 and 5) girls than less mature girls and all boys. The clinical implication of these findings is illustrated by analysis of the sum of RV5 and SV2, one of the criteria for left ventricular hypertrophy, by sex and SMR. No significant difference in the sum is noted for boys across five SMR groups. Girls, in contrast, show a steady decrease in the sum with advancing maturation. These trends are not as clearly shown when subjects are grouped by broad chronologic age ranges, as had been the practice in developing current adolescent ECG tables. These findings suggest that development of standard ECG tables in which SMR and sex have been taken into account might enhance interpretation during adolescence. PMID- 2927999 TI - Genital lichen sclerosus mistaken for child sexual abuse. PMID- 2928000 TI - Growth plate: roentgenologic findings in a case of tyrosinosis. PMID- 2928001 TI - Auriculotemporal syndrome seen clinically as food allergy. PMID- 2928002 TI - Chronic idiopathic intestinal pseudoobstruction: a commonly misdiagnosed disease in infants and children. PMID- 2928003 TI - American Academy of Pediatrics Task Force on Pediatrics AIDS: Infants and children with acquired immunodeficiency syndrome: placement in adoption and foster care. PMID- 2928004 TI - Sickle cell trait and competitive athletics: is there a risk? PMID- 2928005 TI - The Hastings Center Project on Imperiled Newborns: supreme court, jury, or Greek chorus? PMID- 2928006 TI - Guidelines for the determination of brain death in children. PMID- 2928007 TI - Newborn screening for sickle cell disease. PMID- 2928008 TI - Lipid composition of milk from mothers with cystic fibrosis. PMID- 2928009 TI - Statistical power. PMID- 2928010 TI - Brain lesions and extracorporeal membrane oxygenation. PMID- 2928011 TI - Extracorporeal membrane oxygenation and right-sided brain lesions. PMID- 2928012 TI - Rett syndrome. PMID- 2928014 TI - Were the good old days better? PMID- 2928013 TI - Resident stress = spousal stress. PMID- 2928015 TI - Pertussis immunization. PMID- 2928016 TI - The anencephalic controversy. PMID- 2928017 TI - Rape and AIDS. PMID- 2928018 TI - Hemorrhage, phenobarbital, and fluctuating cerebral blood flow. PMID- 2928019 TI - Macrosomia, microphthalmia, and early rapid or sudden infant death: a new syndrome? PMID- 2928020 TI - Bilirubin, intraventricular hemorrhage, and phenobarbital. PMID- 2928021 TI - Klinefelter syndrome and fire-setting behavior. PMID- 2928022 TI - Is Hypaque dangerous? PMID- 2928023 TI - Sports and sickle cell trait. PMID- 2928024 TI - Ethical basis for repealing religious exemptions from child abuse statutes. PMID- 2928025 TI - Renal glycosuria in pyelonephritis. PMID- 2928026 TI - Intrapartum asphyxia and cerebral palsy. PMID- 2928027 TI - Hearing loss and persistent fetal circulation. PMID- 2928028 TI - Fictitious crystalluria. PMID- 2928029 TI - Displacement effects caused by converging lines and dots. AB - Changes induced in orientation were examined under conditions of a dot or full line version of a stimulus consisting of a test and inducing line. 44 subjects visually extended the test line to the surrounding circle on 11 trials and indicated their response by a mark on the circle. Magnitude of illusion was reduced by 54% for the dot version compared with the full-line form, but both produced an illusion significantly greater than zero. A significant practice effect was obtained with full lines but not with the dot form. Results are discussed in terms of lateral inhibition theory and related research. PMID- 2928030 TI - Distributed and massed practice effects on motor performance and learning of autistic children. AB - The purpose of this study was to examine the effect of massed and distributed practice upon the learning by 8 autistic children of rotary pursuit tracking at 20 rpm. The massed practice group of four completed 10 30-sec. trials with 5-sec. rests for 10 consecutive days on the Photoelectric Pursuit Rotor. The distributed practice group completed 10 30-sec. trials with 30-sec. rests for 10 consecutive days on the same device. The results of a 2 x 10 x 10 (group x practice days x trials) analysis of variance with repeated measures on the last two factors indicated that learning occurred for both groups but no differences between groups were significant. It is suggested that further investigations into the applicability of motor learning principles to special populations be conducted using larger groups. PMID- 2928031 TI - Continuous noise, intermittent noise, and annoyance. AB - In a within-subjects design, 18 subjects listened to white noise, the intensity of which was controlled by themselves. They were instructed to choose the intensity they experienced as "clearly annoying." Three kinds of white noise were used: continuous, intermittent regular, and intermittent irregular. In the two intermittent conditions, the proportion of time with the noise on was 50%. The duration of on- and off-periods in the regular condition was 1.15 sec.; in the irregular condition, it varied between 0.25 and 1.65 sec. The subjects chose their "clearly annoying" level three times for each noise type. The results showed that the mean level chosen was 83.9 dB for continuous, 90 dB for intermittent regular, and 89.6 dB for intermittent irregular noise. Pairwise comparisons indicated a significant difference between continuous noise and each of the two intermittent noises while there was no difference between the two intermittent noises. The results are interpreted as indicating that noise-induced annoyance may be a function of the over-all amount of noise rather than the mere presence or absence of intermittency, at least when no concurrent demanding task is performed and when the required annoyance level is set by the subjects themselves. The results further showed that the intensity chosen by the subjects correlated negatively with scores from Weinstein's Noise Sensitivity Scale while the intensity chosen was unrelated to extraversion or neuroticism scores as measured by Eysenck Personality Inventory. PMID- 2928032 TI - Learning disabled students' performance on visual and auditory spelling tests. PMID- 2928033 TI - Field independence as a function of sex, sex-roles, and the sex-role appropriateness of the task. AB - Two experiments were conducted to explain the sex difference in field independence by reference to socialization factors. It was hypothesized that the sex-role appropriateness of the task as masculine or feminine-typed would influence the performance of masculine and feminine women in a manner congruent with their sex-role orientation. 28 pilot subjects and 100 subjects in Study 2 were equally divided between the sexes. Both studies used the Bem Sex-role Inventory, but different versions of the Embedded Figures Test. The over-all results suggested that feminine women varied their performance according to task appropriateness, although not always in a manner congruent with their sex-role orientation. Androgynous individuals and masculine men did not alter their performance. PMID- 2928034 TI - Application of Piotrowski's dark shading hypothesis to Sylvia Plath's poems written before her suicide. PMID- 2928035 TI - Relationship of eye color to winning horseshoe pitching contests. AB - Light-eyed individuals perform some self-paced activities better while dark-eyed individuals perform reactive activities better. In horseshoe pitching contests there were, however, no differences on winning or losing between 21 light- and 25 dark-eyed men at a county fair. PMID- 2928036 TI - Attention and brain damage: a clinical study of response latency under various degrees of uncertainty. AB - Wyns and Bruyer in 1988 proposed a visual attention test that is easy to use and sensitive both to the age of the subjects and the level of uncertainty about the response required. This test was designed as a fine gauge of attention deficits in brain-damaged subjects with poorly structured complaints. We present here a preliminary application of the test to a group of 48 such persons. Analysis of response accuracy indicated that 27 subjects were deficient in this respect. Of the 21 remaining subjects whose reaction times were analyzable, only one-third appeared as entirely normal. PMID- 2928037 TI - Use of factor analysis in the study of alcohol-induced strategy changes in skilled performance on a soccer test. AB - The present study was designed to examine how skilled behaviour changes under the effects of two doses of alcohol (0.5 gm/kg and 1 gm/kg). A battery of perceptual motor reference tests, together with the criterion test of a soccer slalom were given a sample of 48 male volunteers to show how performance strategies changed across the different experimental conditions. Analysis indicated little change between effects of placebo and the lower dose but some change in the composition of performance between placebo and the 1 gm/kg dose. This finding supports further use of factor analysis in the study of skilled behaviour. PMID- 2928038 TI - A possible proximity effect on human grip strength: an attempted replication. AB - A double-blind experiment with 50 adults was conducted to replicate a finding that proximity to sugar reduces human grip strength. Grip strength of the dominant hand was measured by a chart-recording hand dynamometer for 12 trials. For half of the trials, the subject held an opaque, sealed bottle containing sugar; for half of the trials, the subject held a control bottle of equal weight containing sand. Statistical analysis indicated no significant effect of held substance upon grip strength. PMID- 2928039 TI - Effects of eye color on the accuracy of ball throwing of elementary school children. AB - Light-eyed individuals generally perform better at self-paced activities while dark-eyed individuals perform better at reactive activities. In throwing a ball at a target there were no differences between light- and dark-eyed elementary school-age children. Boys hit the target more times than did girls, and older children in upper grades hit the target more often than did younger children in lower grades. PMID- 2928040 TI - Anthropometric design criteria: correction variables for military aircraft. AB - Significant errors in the application of dimensional anthropometric design criteria for tactical military aircraft cockpits have been identified. These errors result from insufficient consideration of previously undefined variables relative to posture, restraint system items, and aviators' personal protection equipment as discussed by McConville and Laubach in 1978. PMID- 2928041 TI - Stressed vowel perception in word recognition. AB - The purpose of this study was to measure subjects' ability to detect deliberate stressed, front-vowel misarticulations embedded in two-syllable words. Reaction times to words with various vowel-height misarticulations were examined for 25 women to assess the effect of a specific vowel height change on listeners' ability to recognize a word. Statistical analysis indicated no significant differences between reaction times to initial, stressed vowel changes along the height dimension, suggesting that subjects responded similarly to all vowel errors on the detection task. This finding provides further evidence that stressed-vowel information may serve as a perceptual anchor in guiding a listener during word recognition. PMID- 2928042 TI - Music preferences and perception of loudness. PMID- 2928044 TI - Measurements of gaze movements while driving. AB - In this study, gaze movements of drivers driving through an intersection were investigated. Gaze movements of drivers in large vehicles were compared with those in small vehicles. There were both similarities and differences in the visual search behaviors of drivers of large and small vehicles. The two groups were similar in that, when approaching an intersection, drivers made repeated saccadic gaze movements; after entering the intersection, saccadic gaze movements were directed ahead in the direction of turning. Differences arose in the frequency and distribution of gaze movements. The number of gaze movements was significantly greater in drivers of large vehicles. The distribution of gaze movements in driving a large vehicle showed a peak at the point 50 to 60 degrees to the right and left of the median plane of the driver. The distribution of gaze movements of drivers of small vehicles showed no peak across the visual field. PMID- 2928043 TI - Decision time and movement time in depression: differential effects of practice before and after clinical improvement. AB - Choice reaction time involves, at least two components of response latency, decision time and movement time. Studies of choice reaction time usually provide values of these two components averaged over a given number of trials. The aim of the present study of depressed subjects was to investigate changes across practice on Decision Time (DT) and Movement Time (MT) before and after clinical improvement. 19 depressed subjects were given two sessions of 50 trials each, one before treatment (Di) and one after recovery (Df). Decision time and movement time exhibited quite different patterns. Decision time significantly decreased with clinical improvement. No significant variation across trials was found, in either session. Movement time values varied across trials but the variations observed on Di and Df were significantly different, whereas before treatment latencies recorded at the end of the session were greater than those scored at the start, the contrary was observed after clinical recovery. No significant difference was found between values of movement time scored at the start of the two sessions. PMID- 2928045 TI - Constancy of individual exponents for inspired lung volume: a comment on Harver (1987). AB - In this paper we made two brief commentaries on Harver's (1987) experiment. The first comment is an observation on the growing area of respiratory psychophysics for which we prefer the name Behavioral Physiology. In the second comment it is suggested that the stable individual differences in the exponent of the psychophysical power law reported by Harver may be an artifact of the psychophysical method employed: category production. PMID- 2928046 TI - Sex differences in time perception. AB - In an experiment on discrimination of duration of auditory stimuli in the range of milliseconds 16 men and 16 women were tested. Men scored better than women in discrimination of duration as well as in required session time. These results were discussed in terms of the assumption of a neurotransmitter-related internal clock and with respect to sex differences in reaction time. PMID- 2928047 TI - Perception of attractiveness by obesity and hair color. AB - In a study of 318 Caucasian college students, obese persons and redheaded men were seen as unattractive compared to the nonobese and other hair colors. The obesity stereotype and the hair-color stereotype appear to be evaluated separately with little interaction. The results imply that a stereotypic characteristic like obesity, which is perceived as being under a person's control, may be evaluated differently than a stereotypic characteristic independent of personal choice such as hair color. PMID- 2928049 TI - Menstrual attitudes and symptoms in Nigerian athletes. PMID- 2928048 TI - Perceptions of health, abilities, and life satisfaction among very old adults. AB - Retrospective, current, and prospective perceptions of health, functional abilities, and life satisfaction were examined in a sample of 40 adults 80 yr. of age and older. Perceptions of decline varied among these variables; correlations with objective measures of health and abilities varied in magnitude. PMID- 2928050 TI - Reminiscence and strategies of performance in rotary pursuit tracking. AB - The maximum speed at which man detects and corrects errors is analyzed on the pursuit rotor. During the prerest performance, scores of about 220 msec. are found, for both extravertive and introvertive subjects. During the postrest performance a crossover effect appeared: extraverts had scores near 60 msec., while introverts did not surpass 100 msec. The results are discussed in the framework of Eysenck and Frith's (1977) theory of reminiscence. PMID- 2928051 TI - Children's Sleep Behavior Scale: normative data on 870 children in grades 1 to 6. AB - A 22-item Likert-type rating scale for parents was developed for screening a broad range of specific sleep-related behaviors of elementary school children. The prevalence of these behaviors was reported by parents for boys (n = 459) and girls (n = 411) in three age groups, less than 8.5 yr., between 8.5 and 11.5 yr., and greater than 11.5 yr. For all age groups, the most prevalent behaviors were restlessness, waking up at night, pleasant dreams, getting up to go to the bathroom, talking while asleep, and complaints about not being able to sleep, while the least frequent were rhythmical movements and crying while asleep. The self-reports suggest that many of the behaviors are underestimated in the literature. Some sex and age differences were found, but the number of siblings, birth order, change in family structure, and educational status of father and mother were unrelated to the sleep variables. Test-retest reliabilities of self reports by these parents to individual items were adequate. PMID- 2928052 TI - Effects of sports instruction on children's self-concept. AB - A sample of 120 children (69 boys and 51 girls), ranging in age from 9 to 14 yr., was administered the Harter Self-perception Profile for Children before and after a 5-wk. program of swimming instruction. It is predicted that children who improve most in swimming will also have the largest gains in athletic self concept. The data supported the prediction for an association between gains in swimming skill and self-concept for certain skill groups. PMID- 2928053 TI - Forms can be recognized from dynamic occlusion alone. AB - Direct and indirect theories of perception differ on whether form perception depends on higher order invariants or on features in the retinal image. The present paper describes a demonstration that an object can be recognized through a higher order pattern (dynamic occlusion) without any of the object's features being displayed. Stimuli consist of computer stimulations of black wireframe objects moving in front of, and occluding, a random layout of point lights on a black background. In this way, no single videoframe of the stimuli displays any of the object's features, and motion of the amodal object in front of the light points is necessary for the form to become visible. The forms can also be recognized when isoluminous colours are used for background and point lights. Finally, it is noted that, if the observer can actively control the motion of the object, e.g., by moving a computer mouse, recognition is enhanced as in Gibson's (1962) experiment on active touch. PMID- 2928054 TI - Validities of the Physical Estimation Scale in predicting running times. AB - Two studies were conducted with the purpose of examining the validity of the 12 item Physical Estimation Scale, developed by Safrit and Wood (1985), as a predictor of running performance. Physical Estimation Scale scores were not significantly related to running time at the 5-mi. distance but were significantly correlated with predicted and actual marathon finishing times. PMID- 2928055 TI - Association between paired subtests of auditory sequential memory administered to preschool children. AB - Auditory sequential memory subtests of the Wechsler Preschool and Primary Scale of Intelligence and the McCarthy Scales of Children's Abilities were administered individually to 20 normal preschool children. Poor performance on the McCarthy words/sentences subtest suggests retention difficulties associated with isolated words in the absence of linguistic context. Correlations of only moderate strength and large unexplained variance indicate poor predictability between subtests despite similarities in content and procedural details. PMID- 2928056 TI - Throwing action from full-cue and motion-only video-models of an arm movement sequence. AB - The purpose of this study was to determine whether videotaped demonstrations of an action which displayed only the motion pattern of a model's limb as compared with one which showed both form and motion provide sufficient information for modelling a given pattern of movement. Video-demonstrations of an arm-movement sequence which ended with a throwing action were shown to adult subjects whose task was to model precisely what they saw. Each demonstration lasted 6 sec. and was shown 6 times. It portrayed the arm of a model, who held a small ball, performing a sequence of movements (flexion and extension of the elbow) which ended in the ball being thrown about 2.5 m with a 'darts-style' action. Three types of demonstration were presented: one showed the whole arm in dark clothing against a light-coloured background, another showed the arm as the relative motion of patches of light situated at the shoulder, elbow, and wrist joints, and the third showed the arm as the relative motion of the upper and lower segments of the arm represented by strips of light-reflectant material. These were the stimuli for the between-groups experimental conditions. Goniometry techniques were used to compare the performance of subjects relative to the model. Analysis showed that the order of the preparatory sequence was correctly produced after 4 trials under all conditions. Range of arm movement in projecting the ball closely approximated that of the model after 4 trials in all conditions. The time taken for the arm to project the ball remained constant across trials under all conditions and was always slower than the demonstrated cadence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2928057 TI - Knowledge about suicide as a function of experience. PMID- 2928058 TI - Manual behavior, lateralization of manual skills and cognitive performance of preschool children. AB - Direction and degree of manual specialization (functional asymmetry between the hands) on a pegboard task, and fine motor ability (total number of pegs inserted) of both hands were correlated with verbal and visuospatial performances for 47 preschool children. No significant differences were found between right-, and left-, and mixed-handers even though the best motor skills were shown by the 6 mixed-handed subjects, who also had the highest scores on cognitive tasks. Verbal and visuospatial performances were not correlated with degree or direction of manual specialization. They were instead correlated with the level of motor ability of both hands. Motor maturation should be viewed, then, as a process that implies a richer motor performance of both hands and could be interpreted as a more specific diagnostic parameter than the traditional indices of handedness in cognitive fields. PMID- 2928059 TI - Mood state changes of women as a function of regular aerobic exercise. AB - The present study examined mood states of aerobic exercisers before and after completing a 15-wk. program. The subjects (ages 18 to 36 yr.) were 86 women enrolled in activity classes at a large state school in the southeast. Subjects were initially classified according to previous exercise habits. Analysis indicated both groups of frequent and infrequent exercisers were similar in mood states. Participation in regular exercise did not significantly change or enhance the mood states from pretreatment measures. Pretest measures of mood states provided poor prediction of posttest measures, indicating extreme variability in subjects' scores. PMID- 2928060 TI - Temporal resolution of the aging tactile sensory system. AB - Oral and nonoral tactile fusion thresholds were obtained for 39 subjects ranging in age from 12 to 76 yr. Regression analysis of the data indicated a trend for fusion thresholds to become poorer with age. Further statistical testing indicated mean threshold and variability differences between subjects when they were placed into four groups according to age. PMID- 2928061 TI - Factor structure of perceptual-motor attributes in normal children: a cross validation. AB - The scores on 22 items of the Purdue Perceptual-motor Survey, administered to 567 normal school children of mean IQ 103 and mean age of 116 mo., were subjected to R-factor analysis by the method of principal factoring with orthogonal varimax rotation. The analysis led to the definition of 10 factors: J, ocular control; K, dynamic balance; L, visual-motor fluency; M, chalkboard; N, unilateral-bilateral coordination; O, upper-lower body differentiation; P, form perception; Q, developmental maturation; R, sex; and S, spatial body perception. The results provide cross-validation for previous studies on the perceptual-motor attributes of normal school children. PMID- 2928062 TI - The possible interaction of Harderian material and saliva for thermoregulation in the Mongolian gerbil, Meriones unguiculatus. AB - Self-grooming in Meriones unguiculatus is associated with saliva spread and the release and spread of Harderian material from the external nares. Saliva spread results in evaporative cooling and Harderian spread insulates the pelage. Two experiments tested the predictions that (1) saliva production and Harderian material decrease systematically following a self-groom, (2) high ambient temperature (34 degrees C) increases saliva production but decreases Harderian release, and (3) low ambient temperature (7 degrees C) decreases saliva production but increases Harderian release. The predictions were generally confirmed, suggesting that short-term and long-term thermoregulatory reactions are differentially affected by ambient temperatures. Thus, an animal will tend to emphasize saliva production when evaporative cooling is needed and will exaggerate Harderian release when insulation of the pelage is required. PMID- 2928063 TI - Bizarre imagery in paired-associate learning: an effective mnemonic aid with mixed context, delayed testing, and self-paced conditions. AB - Recent findings have indicated that bizarre imagery can be an effective mnemonic aid with delayed testing, a context of mixed materials, and an adequate stimulus presentation pace, so we hypothesized an interaction among these variables. Using a variation of the McDaniel and Einstein 1986 methodology, 40 undergraduates were each randomly presented three paired-associate lists (i.e., normal, bizarre, and mixed). The sentences within each list consisted of stimulus-response pairs of high-imagery nouns. 20 of these subjects participated in an immediate cued-recall condition for each list while the remaining ones were tested after a 1-wk. retention interval. Subjects were further subdivided depending on whether the presentation pace was forced or not. As predicted, a three-way interaction was found, with bizarre imagery benefiting immediate recall under a combined mixed context, self-paced condition; with delayed recall, however, context was the determining factor in performance (and not presentation pace). PMID- 2928064 TI - Effects of preshot routine on free-throw shooting. AB - The effect of prohibiting the use of a preshot routine on free-throw shooting in competitive situations was investigated. 25 male high school basketball players were instructed to attempt 50 free throws alternating in blocks of 10 between the use of their preshot routine and shooting without it. To make the situation competitive, subjects were run in groups of five and their performance was recorded on a large easel placed to the side of the free-throw line. A significantly larger number of baskets were made in the preshot routine condition than without the routine. A competitive situation led to a greater decrement in baskets than had been reported in 1986 by Lobmeyer and Wassermen during noncompetitive free-throw shooting. PMID- 2928065 TI - Reliability of heart-rate reactivity to a psychological stressor. AB - Reliability of heart-rate reactivity responses to a timed and competitive mental arithmetic stressor was investigated in a sample of 40 students. Analysis indicated that significant differences between groups of high and low heart-rate reactivity subjects were consistent over a period of 4 to 6 wk., with no significant effects from mental arithmetic performances. PMID- 2928066 TI - The cerebellar-vestibular predisposition to anxiety disorders. AB - To test for a cerebellar-vestibular (CV) predisposition to anxiety disorder, 402 consecutively referred subjects with varying anxiety symptoms were separated into eight DSM-III--R diagnostic categories and evaluated for CV dysfunction, using neurological and electronystagmographic (ENG) examinations. Of the total sample, 94% evidenced CV-dysfunction on the basis of two or more abnormal neurological or ENG parameters per subject. All DSM-III--R diagnostic anxiety-disorder categories contained a high percentage of abnormal neurological and ENG parameters, regardless of the size of the subsample. Moreover, each DSM-III--R subsample of anxiety disorders contained additional coexisting symptoms of anxiety sufficient to overlap with and form the basis for diagnosis of most other DSM-III--R anxiety disorder categories. Such findings suggested that anxiety disorders, regardless of surface descriptions and DSM-III--R category, have a common denominator with varying symptom-shaping mechanisms and that this denominator is significantly CV based. Although the above findings do not justify cause and effect convictions, they have provided crucial insights leading to (1) a proposed functional classification based on underlying determining mechanisms rather than on descriptions of symptoms, (2) a possible relationship between anxiety and learning disorders, and (3) a new method of treating these disorders by means of CV-stabilizing medications in conjunction with traditional approaches. Needless to say, independent and controlled studies, including comparisons with "normal" persons, are required for both validation and elucidation of those specific determining vs compensatory mechanisms and related diagnostic parameters crucial for symptom formation. PMID- 2928067 TI - Peripheral apparent motion as a function of location, contrast, and direction of stimulus motion. AB - This study investigated the perception of the direction of peripheral apparent motion as a function of stimulus location in the peripheral visual field, stimulus contrast, and the direction of the apparent motion. Results indicated that each of these independent variables was significant as a main effect while the interactions were not. PMID- 2928068 TI - Abnormal optokinetic and perceptual span parameters in cerebellar-vestibular dysfunction and learning disabilities or dyslexia. AB - To measure the ocular fixation and sequential scanning dysfunction assumed responsible for the visual reading symptoms which characterize dyslexia or learning disabilities, an optokinetically based tracking method was devised. This method quantitatively demonstrated significantly reduced fixation, tracking, and perceptual or visual-span scores as well as "movement illusions" for 70 cerebellar-vestibular dysfunctioning persons with learning disabilities vs 70 controls. Such data tended to validate the hypothesis that cerebellar-vestibular determined fixation and tracking mechanisms predispose dyslexic or learning disabled individuals to visual reading disorders. Moreover, a newly revised method is presented which may prove useful in rapidly screening and diagnosing cerebellar-vestibular-determined reading and learning disorders from those of other origins. Additional independent studies using significantly larger samples and asymptomatic or "normal" controls are required for further validation and development of the method. PMID- 2928069 TI - A cerebellar-vestibular explanation for fears/phobias: hypothesis and study. AB - To clarify and test the cerebellar-vestibular (CV) basis of fears/phobias, responses of 4000 learning disabled children, adolescents, and adults with neurological and electronystagmographic (ENG) evidence of CV-dysfunction were analyzed for anxiety-related symptoms. Of this sample, 64.6% indicated fears/phobias; females were significantly more predisposed; mixed-handedness was significantly related to fears of heights and reduced vestibular response or asymmetric vestibular functioning. Also, adults had a higher incidence of the specific fears/phobias characterizing agoraphobia than children and adolescents. Analysis of factors reported as triggering the fears/phobias led to (1) a classification and theory of fears/phobias, obsessions/compulsions, and related anxiety symptoms based on realistic or traumatic, neurotic, and CV- or other CNS based mechanisms rather than on DSM-III--R surface descriptions; (2) an understanding of the relationships between mitral valve prolapse, agoraphobia and panic episodes, as well as depression; and (3) new insights into differential diagnosis and selective treatment. PMID- 2928070 TI - Effects of age and sex upon availability of responses on a word-association test. PMID- 2928071 TI - A home evaluation of a behavioral response measure of sleep/wakefulness. AB - 15 women and 3 men enrolled in a first-year undergraduate psychology course participated in a study concerned with evaluating the home use of a behavioral response monitor of sleep/wakefulness. The subjects, representing a range of fairly poor to good sleepers, used the device for three consecutive nights in their own homes. The 1967 Monroe Questionnaire was used to differentiate "good" sleepers from "poorer" sleepers. The behavioral response system indicated that subjects could adequately report how long they slept but consistently underestimated their number of arousals and could not reliably specify sleep onset latency. The behavioral response measure was an effective and economical means of obtaining in-home objective sleep data and holds potential for clinical evaluation of disorders of initiating and maintaining sleep. PMID- 2928072 TI - Overprediction and blocking in the McCollough aftereffect. AB - The Rescorla-Wagner theory (Rescorla & Wagner, 1972) of associative learning offers specific predictions about the associative strength of CS-US pairs when two or more CSs are conditioned to the same US separately and subsequently paired in a compound with the same US. The magnitude of orientation-contingent color aftereffects (AEs) was used as an index of associative strength in this study. The results of experiments using an "overprediction" (Rescorla, 1970) and a "blocking" (Kamin, 1969) paradigm conformed to the predictions of the Rescorla Wagner theory. In Experiment 1, AEs were established simultaneously for horizontal-vertical and diagonal patterns. When observers subsequently viewed compound induction patterns, AE magnitude was found to be significantly decreased, relative to a condition in which observers did not view such an induction pattern. In Experiment 2, AE magnitude for a given test pattern following inspection of compound induction stimuli was significantly reduced by inspection of the other component prior to viewing the compound induction stimuli. The applicability of associative learning and feature-adaptation models of the McCollough effect is discussed. PMID- 2928073 TI - Quality-specific effects of aging on the human taste system. AB - Elderly persons are known to have elevated taste thresholds, with those for bitter more affected by age, for example, than those for sweet. Do analogous quality-specific effects occur at suprathreshold levels? Young (mean age = 20.3 years, SD = 2.99) and elderly (mean age = 72.5 years, SD = 4.58) subjects made magnitude estimates of sweetness, bitterness, sourness, and saltiness for the unmixed components sucrose, caffeine, citric acid, and NaCl at three concentration levels for each. They also made magnitude estimates of the separate taste qualities in two-component mixtures of sucrose with each of the other three qualities, at various levels of the two components in each mixture. Magnitude estimates of taste intensity were interweaved with magnitude estimates of the heaviness of six weights, which subjects were to judge on the same subjective intensity scale: This is the calibration feature of the method of magnitude matching, and permits the comparison of elderly and young subjects on the absolute intensity of tastes. When unmixed components were judged, elderly subjects found the characteristic tastes of caffeine and citric acid less intense than, but those of sucrose and NaCl as intense as, younger subjects did. In judging mixtures, the elderly found bitterness, but not the other three qualities, less intense than did the young subjects. PMID- 2928074 TI - Motion aftereffects with horizontally moving sound sources in the free field. AB - A horizontally moving sound was presented to an observer seated in the center of an anechoic chamber. The sound, either a 500-Hz low-pass noise or a 6300-Hz high pass noise, repeatedly traversed a semicircular arc in the observer's front hemifield at ear level (distance: 1.5 m). At 10-sec intervals this adaptor was interrupted, and a 750-msec moving probe (a 500-Hz low-pass noise) was presented from a horizontal arc 1.6 m in front of the observer. During a run, the adaptor was presented at a constant velocity (-200 degrees to +200 degrees/sec), while probes with velocities varying from -10 degrees to +10 degrees/sec were presented in a random order. Observers judged the direction of motion (left or right) of each probe. As in the case of stimuli presented over headphones (Grantham & Wightman, 1979), an auditory motion aftereffect (MAE) occurred: subjects responded "left" to probes more often when the adaptor moved right than when it moved left. When the adaptor and probe were spectrally the same, the MAE was greater than when they were from different spectral regions; the magnitude of this difference depended on adaptor speed and was subject-dependent. It is proposed that there are two components underlying the auditory MAE: (1) a generalized bias to respond that probes move in the direction opposite to that of the adaptor, independent of their spectra; and (2) a loss of sensitivity to the velocity of moving sounds after prolonged exposure to moving sounds having the same spectral content. PMID- 2928075 TI - Human optokinetic nystagmus: competition between stationary and moving displays. AB - We reported earlier that occlusion of the central retina and stationary edges have highly interactive effects on the gain of optokinetic nystagmus (OKN; Murasugi, Howard, & Ohmi, 1986). In this study, we explored this effect in more detail. A central occluding band of variable height, flanked by vertical bars, was superimposed onto an array of dots moving at 30 degrees per second. The height of the occluding band required to abolish OKN increased with the separation of the vertical bars. For bars 3.5 degrees apart, OKN was abolished in most subjects when a band only 6' high ran between them. For bars 75 degrees apart, a band at least 20 degrees in height was required to abolish the response. The effects of the stationary figure depended to some extent on the subject's attention, but only at intermediate values of bar separation. Both low- and high level mechanisms are proposed to account for the results. PMID- 2928076 TI - Mirror reversal by blind subjects in cutaneous perception and motor production of letters and numbers. AB - A letter drawn on the forehead is often perceived as its mirror reversal. Similarly, people produce mirror reversals when asked to write a letter on the underside of a table at which they are sitting. We varied the orientation and position of the stimulated or inscribed surface, and found several examples of these two mirror-reversal phenomena in blind subjects (who had no, or very little, visual experience), as well as in sighted subjects. Furthermore, the mirror-reversal rate of the two groups of subjects as a function of orientation and position of the surface was highly correlated. Thus, the mirror-reversal phenomena should be attributed to a nonvisual, spatial cognitive scheme that is perhaps shared by sighted and blind subjects. PMID- 2928077 TI - Semantic priming: subliminal perception or context? AB - Briefly presented, masked priming stimuli that cannot be identified by themselves can affect the processing of subsequent targets. The effect, which is sometimes viewed as a demonstration of unconscious processing, has been linked to the subliminal perception literature. Experiments 1 and 2 indicated that the identification of primes in the context of semantically related targets is superior to the identification of primes presented alone, and that the identification of primes in the context of semantically unrelated targets is inferior to the identification of primes presented alone. Experiment 3 indicated parallel findings in a recognition task. Consequently, an explanation of semantic priming in terms of the interactive nature of stimuli that are near to one another in time seems preferable to one based upon concepts of unconscious processing and subliminal perception. PMID- 2928078 TI - Perceptual localization of visual stimuli flashed during saccades. AB - Subjects were asked to make a saccade to a visual target flashed in the dark during a prior primary saccade, and to report its apparent position by moving an adjustable light spot to that position. When targets were presented at the beginning of the primary saccade, subjects perceptually mislocated them in the direction of the saccade, whereas when targets were presented immediately before the end of the primary saccade, the flashed targets were mislocated in the opposite direction. The perceptually localized position of the target was primarily determined by its retinal position. However, at all actual and retinal positions of the target, the localized position shifted from the position that would be predicted if the location of the target was determined only by its retinal position to the prior primary saccade direction. The results were discussed in relation to extraretinal eye position signals. Subjects moved their eyes not to the actual position of the target, but to its apparent position. In some trials, there was a discrepancy between perceptual and oculomotor localization, which was interpreted as having been caused by the imprecise localization ability of the oculomotor system. PMID- 2928079 TI - Shifting of attentional focus within and about a visual display. AB - If several positions must be attended in a large visual display, does the efficiency of performance vary as a function of the display distance between these to-be-attended positions? Two previous experiments (Podgorny & Shepard, 1983; Shaw, 1978) gave conflicting answers. In the present experiments, eight letter circular displays were briefly presented. On each trial one, two, or three positions of the display were cued or precued. The number of noncued display positions intervening between the cued locations varied from zero to three. The subjects' task was to rapidly discriminate between two target letters. Although reaction time was found to increase with increases in the number of cued locations, no significant or suggestive effects were found for the spacing or distance between the cued locations. The evidence strongly suggests that the subjects serially searched the cued locations, which further implies that attention can index locations in the visual field at a speed that is independent of the distance between these locations. PMID- 2928080 TI - On listening where we look: the fragility of a phenomenon. AB - The role of eye position information has been the subject of some debate in the literature on the visual facilitation of auditory localization and attention. In one particularly compelling study, Reisberg, Scheiber, and Potemken (1981) found that fixation position strongly influenced subjects' recall performance in a binaural selective-listening task. The present paper describes repeated failures to demonstrate the eye position effect under conditions similar to those of the original study, thus challenging the robustness of this oft-cited phenomenon of "listening where we look." PMID- 2928081 TI - Pattern-contingent color aftereffects on noninduced patterns. AB - In a series of experiments, we found that in addition to expected reports of color aftereffects on patterns viewed during induction, reliable and predictable reports of color were given by subjects to patterns they did not view during induction. These reports to noninduced patterns were generally to patterns that were orthogonal to the patterns seen during induction. Induction with, for example, a red vertical grating led to appropriate aftereffects (i.e., green) on that vertical pattern and to the complementary aftereffect (i.e., pink) on a horizontal grating. We suggest that such color aftereffects on noninduced patterns are based on a shift in the activity of orientation coding mechanisms as a result of viewing the inducing patterns. We further propose that the results are consistent with the Lie transformation group theory of neuropsychology and that they add to a growing body of research demonstrating the applicability of this theory to the understanding of pattern-contingent color aftereffects. PMID- 2928082 TI - The case of Tertius Lydgate. PMID- 2928083 TI - Glutathione-dependent inactivation of sodium-dependent phosphate transport across rat renal brush-border membrane. AB - Thiol/disulfide is fundamental in protein function; we previously observed an inhibitory effect of thiol oxidants on the Na-dependent phosphate (Pi) uptake into renal brush border membrane vesicles (BBMV). We examined whether oxidation of glutathione (GSH) is involved in the mechanism. Vesicular thiols were measured by liquid chromatography. BBMV were incubated with reagents before an influx of Pi. Diamide (5 mM) reduced the capacity of the Pi uptake. Subsequent treatment with dithiothreitol (5 mM) blocked the inhibitory effect of diamide. Vesicular GSH was not modified only by the incubation, whereas it was oxidized by the treatment with diamide, and reduced by dithiothreitol. Furthermore, in vivo treatment with cAMP provided GSH-depleted BBMV without any influence on Pi uptake. Diamide did not inhibit the transport of Pi into GSH-depleted vesicles, but it did inhibit the uptake when GSH was introduced into the vesicles. In conclusion, a GSH-dependent mechanism is involved in the inhibitory effect of diamide on sodium-dependent Pi transport across the renal brush-border membrane. PMID- 2928084 TI - Temporal fluctuations in regional myocardial flows. AB - Considerable spatial heterogeneity has been observed in regional myocardial blood flow in isolated hearts and in both anesthetized and conscious animals. In order to study how local blood flow varies with time, the data obtained by King et al. (1985) from ten awake, healthy baboons were analyzed to estimate the role of temporal fluctuations. Four to six distributions of regional flows were estimated at intervals of 4 min to 27 h, using 15 mu diameter microspheres and dividing each heart into 204 locatable pieces (average piece mass = 0.17 g). The technique averages over the 40 s of the injection giving no measure of fluctuations over a few seconds. The temporal variation in regional blood flow, expressed as the relative dispersion (SD/mean) of the temporally separated measurements about the mean flow for each piece and corrected for methodological noise, was 12% for the whole heart (10828 observations). For the left ventricle, the temporal variation was 10% (8806 observations), for the right ventricle 14% (1455 observations), and for the atria 22% (567 observations). On a relative basis, temporal fluctuation was greatest in regions having low flows. Since the magnitude of the changes in flow distributions was the same after 4 min as it was in several hours, we conclude that much of the "twinkling" is a high frequency phenomenon occurring over seconds to a few minutes. Further, it is concluded that regional myocardial blood flow in conscious primates is relatively stable with time, temporal fluctuations causing only about one third of the variation between regions. PMID- 2928085 TI - Total muscle mitochondrial volume in relation to aerobic capacity of horses and steers. AB - The relationship between maximal oxygen consumption rate (VO2max) and mitochondrial content of skeletal muscles was examined in horses and steers (n = 3 each). Samples of the heart left ventricle, diaphragm, m. vastus medialis, m. semitendinosus, m. cutaneous thoracicus and m. masseter, as well as samples of muscles collected in a whole-body sampling procedure, were analyzed by electron microscopy. VO2max per kilogram body mass was 2.7 x greater in horses than steers. This higher VO2max was in proportion to the higher total volume of mitochondria in horse versus steer muscle when analyzed from the whole-body samples and from the locomotor muscle samples. In non-locomotor muscles, total mitochondrial volume was greater in horses than steers, but not in proportion to their differences in VO2max. The VO2max of the mitochondria was estimated to be close to 4.5 ml O2.ml-1 mitochondria in both species. It is concluded that in a comparison of a highly aerobic to a less aerobic mammalian species of similar body size, a higher oxidative potential may be found in all muscles of the more aerobic species. This greater oxidative potential is achieved by a greater total volume of skeletal muscle mitochondria. PMID- 2928086 TI - Central vasomotor control of the rabbit portal vein. AB - Contractile responses of the portal vein of the anesthetized rabbit were measured quantitatively by plethysmography during transmural electrical field stimulation (TES, 0.8 ms and 15 V) and during the cerebral ischemic pressor response at various volemic states. To evoke the cerebral ischemic response, the route of blood supply to the brain was surgically restricted to the right internal carotid artery, the artery was then compressed in a stepwise fashion by a micrometer device. The maximum contractile response of the portal vein segment that could be evoked by cerebral ischemia corresponded in magnitude to that produced by TES of 10-11 Hz. The contractile response began when the internal carotid blood flow was reduced to 4 ml/min from its normal value of 13.8 +/- 1.2 (mean +/- SE) ml/min and reached a maximum at 0 ml/min. The maximum contractile response was an increase of 26% from control value under normovolemic condition, 20% after hemorrhage and 31% after volume loading. It was estimated that the contractile response in normovolemia was 95% neurogenic, the rest was thought to be of humoral origin. PMID- 2928087 TI - Endogenous adenosine improves work rate to oxygen consumption ratio in catecholamine stimulated isovolumic rat heart. AB - This study examines the possibility that endogenous adenosine modulates efficiency in isovolumic perfused rat hearts stimulated with isoproterenol or norepinephrine. Efficiency in these hearts is calculated as the rate of pressure work divided by the myocardial oxygen consumption. Within 2 min of infusion of isoproterenol (50 nM), heart rate increased by 35%, the rate pressure product by 290%, oxygen consumption by 142%, and efficiency by 67%. Infusion of adenosine deaminase (2-4 IU/ml), or 8-phenyltheophylline (5 microM), into stimulated hearts augmented the increase in heart rate by 40-45%, rate-pressure product by 18-20%, and oxygen consumption by 50-55%. Efficiency was reduced by 30-35%. Adenosine release into the coronary venous effluent increased from 195 +/- 20 pmol/min/g to 2400 +/- 180 pmol/min/g after 5 min. A similar pattern of results was observed when norepinephrine (0.1 mM) was used. The results indicate that extracellular adenosine, released by catecholamine treatment, inhibits the effects of the catecholamines on rate and contractility. Consequently, adenosine reduces cardiac work (rate-pressure product), but in so doing, improves efficiency. PMID- 2928088 TI - Cardiac vagal and sympathetic nerve responses to baroreceptor stimulation in the dog. AB - The effects of ascending stepwise pressure changes in the isolated carotid sinuses on cardiac vagal and sympathetic nerve activities were studied in anesthetized, open chest dogs. The steady state responses of the cardiac vagal and the sympathetic nerve activity and arterial blood pressure were plotted against the sinus pressure and the relations were approximated by the normal distribution function (response curve). The sinus pressure- vs. "reflex gain" relations (reflex gain curve) were approximated by the normal density function. The maximum gain and the "range of change" were found to be greater for the vagal than for the sympathetic and arterial pressure responses. The sinus pressure values derived from "response curves" and "reflex gain curves" for vagal and sympathetic nerve responses were close to each other, while these values and those obtained from arterial pressure responses were considerably apart. It was concluded that: (1) The cardiac vagal neurons are more sensitive to the baroreceptor input than the sympathetic neurons; (2) The similar type of baroreceptor afferent inputs reach the cardiac vagal and the sympathetic structures which are controlling the autonomic outflows. PMID- 2928089 TI - Perturbation of red blood cell flow in small tubes by white blood cells. AB - The flow of blood in the microcirculation is facilitated by the dynamic reduction in viscosity (Fahraeus-Lindquist effect) resulting from the axial flow of deforming erythrocytes (RBCs) and from the decrease in the ratio of cell to vessel diameter. RBC velocity exceeds that of average fluid velocity; however the slower moving white blood cells (WBC) perturb flow velocity and the ratio of cell to vessel diameter by obstructing red cell flow through formation of "trains" of red cells collecting behind the white cell. This effect of white cells was studied quantitatively in a model in vitro tubes less than 10 microns in diameter with the demonstration that flow resistance increases linearly with white cell numbers up to 1,000 WBC/mm3 at tube hematocrit of 17.7%. The increase in resistance exceeds the flow resistance of WBC and appears to relate directly to train formation. A mechanical model of train formation developed to predict WBC influence in flow resistance over the range of WBC studied reasonably fits observed WBC effects. PMID- 2928090 TI - Measurement of element content in isolated papillary collecting duct cells by electron probe microanalysis. AB - A method was developed to measure the element content of freshly isolated papillary collecting duct (PCD) cells by electron probe microanalysis in a scanning electron microscope. After isolation, the cells were transferred onto a Thermanox support by centrifugation and the extracellular medium was removed by brief exposure to buffered ammonium acetate; cryofixation, freeze-drying, and coating with carbon followed. Under visual control in the scanning electron microscope the Na, Cl, K and P content of cell clusters (about 30 cells/cluster) was then measured by X-ray microanalysis. Cells incubated in control medium showed potassium:sodium ratios identical to those determined previously in cryosections of the same cells. In ouabain-treated cells sodium influx and potassium efflux was demonstrated. Potassium left the cells with a t1/2 of 21.7 min. The t1/2 of Na influx was 12.6 min for the first 15 min of incubation, whereafter further influx was markedly slower. Ouabain-induced sodium influx was inhibited 40% by amiloride. These results indicate that X-ray microanalysis can be applied to analyze the ion content of isolated cell clusters derived from the papillary collecting duct. Using ouabain and amiloride as inhibitors the suitability of the method to identify transport systems is demonstrated. PMID- 2928091 TI - Ionic and osmotic dependence of secretion from permeabilised acini of the rat pancreas. AB - Many types of secretory granule have been observed to swell as a result of cell stimulation implying a degree of osmotic control, although the regulation of granule fusion with the apical plasma membrane is not clearly understood. In the present study we have investigated the ionic and osmotic dependency of basal and stimulated 3H-protein release from rat pancreatic acini, permeabilised by either digitonin or high voltage electric discharge. Acini were stimulated with either cholecystokinin-pancreozymin octapeptide (CCK-8), carbachol (CCh), or with phorbol ester (TPA) plus cAMP. Stimulated secretion was significantly reduced when 130 mmol/l Cl- in the buffer was replaced by I-, NO3-, SCN- or cyclamate-. Secretion in Cl- buffers was inhibited by the anion transport inhibitor 4,4 diisothiocyanatostilbene-2,2-disulfonic acid (DIDS), by 40% of the control response. Neither Na+ nor N-methyl-D-glucamine+ could replace K+ in the buffer. Ba2+ and quinine, which block K+ conductance pathways, inhibited stimulated secretion by 50%. Finally, stimulated secretion from leaky cells was nearly abolished by doubling buffer osmolarity. The data suggest that when the cell is stimulated, a Cl- and a K+ permeability appear in the zymogen granule membrane and the ions enter down their electrochemical gradients. The increased intragranular osmolarity results in granular swelling which is intimately associated with secretion. PMID- 2928092 TI - Three potassium currents in mouse motor nerve terminals. AB - A study of the K conductance of the presynaptic membrane has been performed in the triangularis sterni muscle of the mouse. External currents generated in the presynaptic terminals upon invasion by action potentials have been recorded using microelectrodes inserted into the perineurium of preterminal nerve bundles. The voltage-dependent K current could be pharmacologically dissected into fast (IKf) and slow (IKs) components. While both are sensitive to 3,4-diaminopyridine (3,4 DAP), only IKf is sensitive to tetraethylammonium (TEA). Uranyl (100-200 microM) and guanidine (5-10 mM) produced a near complete block of IKf and IKs, which can explain their facilitatory effect upon transmitter release. The third K current of presynaptic terminals is Ca2+-dependent, but was activated also by Sr2+. This current could be suppressed by nanomolar doses of charybdotoxin; it is also sensitive to TEA but not to 3,4-DAP, uranyl or guanidine. PMID- 2928093 TI - Ca-induced Ca release from the sarcoplasmic reticulum of isolated myofibrillar bundles of barnacle muscle fibres. AB - Isometric tension and aequorin light were recorded from isolated myofibrillar bundles (diameter 0.2 mm) of barnacle muscle fibres to examine Ca release from the sarcoplasmic reticulum (SR). Transfer of a bundle from a pCa 6.7 solution to a pCa 5.8 solution, both buffered with 0.1 mM EGTA, resulted in a phasic increase in myofibrillar free Ca2+ which was superimposed on a slow rise to a steady level and a fast rise in tension. The peak of the free Ca2+ response was higher than the free Ca2+ in the bulk solution. Treatment of the bundle with the detergent Brij to destroy the SR membranes abolished the phasic rise in Ca2+ and considerably reduced the amplitude of contraction. A second challenge of a bundle to the pCa 5.8 solution without prior reloading of the SR Ca store gave a much reduced phasic component. When a pCa 5.8 solution with 1.0 mM EGTA buffering was used, the phasic rise in myofibrillar free Ca2+ could not be detected and the rise in tension was four times slower than with 0.1 mM EGTA. The results are consistent with the operation of a Ca-induced Ca release mechanism in the SR membrane of this crustacean muscle. PMID- 2928094 TI - Intracellular pH measurement in primary monolayer cultures of rat epididymal cells. AB - Intracellular pH (pHi) of primary monolayer cultures of the rat epididymal cells has been measured using fluorescent dye 2',7'-bis(carboxyethyl)-5(6) carboxyfluorescein (BCECF). When incubated in normal Krebs-Henseleit (K-H) solution containing 25 mM HCO3, cell monolayers exhibited a basal pHi of 7.17 +/- 0.08. Amiloride (0.5 mM) added to the cell monolayers caused an immediate and sustained fall in pHi by 0.43 +/- 0.05 pH unit. Similar effects were produced when extracellular Na ions were substituted by N-methyl-D-glucamine. Addition of SITS (0.5 mM) or DPC (0.6 mM) resulted in a transient intracellular alkalosis. Adrenaline (0.23 microM) caused a fall in pHi by 0.33 +/- 0.05 pH unit. The fall was slow and was achieved after 30 min (half time 9.9 min). The effect of adrenaline was reversible upon washing and was blocked by propranolol (2 microM). The effect of adrenaline was mimicked by forskolin (10 microM) and Br-cAMP (0.5 mM) which caused a fall in pHi by 0.35 +/- 0.03 and 0.35 +/- 0.02 pH unit respectively. Addition of diphenylamine-2-carboxylate (DPC, 0.6 mM) to the cuvette completely blocked the intracellular acidification produced by adrenaline or forskolin. However, addition of SITS (0.5 mM) did not prevent the intracellular acidosis induced by these agonists. If monolayers were first treated with forskolin (10 microM), the intracellular pH fell, when stabilized, subsequent addition of amiloride caused a further fall in pHi. When incubated in a Cl-free solution (Cl substituted by gluconate), cell monolayers exhibited a pHi of 7.23 +/- 0.07 (values not significantly different from monolayers incubated in HCO3 solution).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2928095 TI - Changes in velocity of shortening, power output and relaxation rate during fatigue of rat medial gastrocnemius muscle. AB - The force-velocity characteristics of rat medial gastrocnemius muscle have been determined by measuring the force sustained during constant velocity releases of the muscle stimulated in situ at an ambient temperature of 26 degrees C. The velocity of unloaded shortening was determined using the "slack" test and rate of relaxation from the half time of force loss at the end of stimulation. Measurements were first made on fresh muscles using short contractions and then during a series which consisted of a 15 s contraction (fatigued muscle), followed by 15 min recovery and a 1 s contraction (recovered muscle). After a 5 min recovery period the sequence was repeated. Comparison was made between the fatigued and recovered state in each preparation in order to allow for any change in the preparation during the course of the experiment. After 15 s contraction the fatigued muscles showed a marked reduction in all parameters measured. In fatigued muscles the isometric force fell to 48 +/- 15% (mean +/- SD) and there was a decrease in maximum velocity of shortening to 66%. These changes in the force-velocity relationship were accompanied by slowing of relaxation so that the half time of relaxation nearly doubled. The consequence of these changes was that the maximum power output was reduced by a much greater extent than was the isometric force (75% vs. 52%). It is suggested that the changes in force-velocity characteristics reflect a reduction in cross-bridge cycling in fatigued muscle. PMID- 2928097 TI - The use of the creatine kinase reaction to determine free energy change of ATP hydrolysis in anoxic cardiomyocytes. AB - In isolated cardiomyocytes from adult rat heart the free energy change of ATP hydrolysis (dG) was determined under conditions of substrate-free anoxia. Changes of free cytosolic ADP concentrations, needed for the calculation of dG, were determined by two indirect methods since a direct measurement is not feasible: (i) via the mass action ratio of the creatine kinase reaction (CK) assuming near equilibrium conditions, and (ii) via quantification of the net hydrolysis of ATP to ADP by a detailed balancing of possible contribution to Pi production. Both approaches gave virtually identical results, showing that in anoxia only 6% of the ATP hydrolysed are hydrolysed to ADP and 94% completely to adenosine and further degradation products. The convergence of both methods also indicates that in this model the CK reaction is indeed catalysed near its equilibrium. Therefore estimations of free ADP and dG using its mass action ratio are valid. In anoxic cardiomyocytes dG values fell from 57 kJ/mol in normoxia to 42 kJ/mol after 120 min anoxia, corresponding to a decrease of ATP contents from 24 to 4 nmol/mg protein. PMID- 2928096 TI - Dynamics of metabolic responses to prolonged elevation of circulating adrenaline in resting and exercising rats. AB - The purpose of this study was to follow the time course of metabolic responses to hyperadrenalinemia sustained up to 3 days. Hyperadrenalinemia was produced in rats by s.c. implantation of tablets releasing adrenaline (A) at a constant rate (1.6 micrograms x min-1). After 6, 12, 24 and 72 h of hyperadrenalinemia and 3 days after the tablet removal rats were sacrificed and liver, 3 types of muscles and blood samples were taken. Each time 14 rats were used: 7 of them were sedentary and 7 performed treadmill endurance exercise before decapitation. Sham operated animals served as controls. In preliminary experiments working ability was examined in 10 hyperadrenalinemic and 10 control rats. Duration of exercise until exhaustion was reduced in hyperadrenalinemic rats on the average by 40%. In sedentary rats, hyperglycemia, marked depletion of liver glycogen (by approx. 80%) and muscle glycogen (by 60-80%) as well as an elevation (2-4 times) of muscle lactate (LA) were found only during the first day after A-tablet implantation. At the end of the experiment these values approached the control ones. Muscle contents of ATP and creatine phosphate (CrP) were decreased by approx. 20% and 30-60%, respectively. Plasma FFA were markedly enhanced, varying in the time-course of the experiment from 0.8 to 1.4 mmol x l-1. Post-exercise values for blood glucose, liver and muscle glycogen were always lower in hyperadrenalinemic rats than in controls sacrificed after time-matched exercise (30 min). Circulating FFA decreased during exercise at all time points following A-tablet implantation, but they were still above the post-exercise levels in sham operated rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2928099 TI - Versatile supplement device with remote control for the control of patch clamp experiments. AB - A versatile device for a patch-clamp amplifier is described. This device contains: (i) an acoustic indicator to monitor the input resistance of the patch pipette, which is used in search-mode to indicate the formation of seals; (ii) two pulse generators; and (iii) a staircase generator to produce various pulse and voltage step programs; (iv) a low-pass filter which is used to filter the output of the patch clamp amplifier; and (v) a remote control which is used to control the entire patch clamp experiment. This remote control is used to switch between search-, current clamp-, and voltage clamp-mode, to activate the respective stimulus potential programs, and to control the tape recorder. This electronic device can be easily connected to patch clamp amplifiers. PMID- 2928098 TI - Effects of external calcium on acetylcholine-evoked increases in membrane capacitance in rat pancreatic acinar cells. AB - Effects of external calcium on acetylcholine-induced increases in membrane capacitance and conductance were investigated with the patch-clamp technique in combination with the phase-sensitive detection method, in single dialysed pancreatic acinar cells of rats. Both increases depended on an increase in [Ca2+]i, and a high concentration of EGTA in the cell-dialysing solution made ACh ineffective. In acinar cells exposed to a bathing solution containing the normal concentration of Ca2+ (2.5 mM CaCl2), the increase in membrane capacitance was transient and synchronous with that in membrane conductance (current) in response to 0.2 microM acetylcholine. However, in a bathing solution without CaCl2 and with EGTA (0.2 mM), the increase in membrane capacitance was sustained after the membrane conductance recovered to the original level during the ACh-stimulation. The evidence suggests that external calcium facilitates either the resealing of the fusion- or fission-pores formed at the contact between the secretory granule and the luminal cell membrane, or the membrane retrieval (endocytosis) in Ca2+ dependent exocytosis. PMID- 2928100 TI - Review of research in nursing education. Volume II. PMID- 2928101 TI - Learning styles: theory and use as a basis for instruction. PMID- 2928102 TI - Mandatory continuing education: a review of the empirical evidence. PMID- 2928103 TI - Clinical judgment: a comparison of theoretical perspectives. PMID- 2928104 TI - Administrative leadership and faculty scholarship: research on nursing faculty and deans. PMID- 2928105 TI - Curriculum building in nursing: a process. PMID- 2928106 TI - Nursing student census with policy implications 1988. PMID- 2928107 TI - Definitions and nomenclature of nucleic acid structure components. AB - We report here recommendations for the definitions and nomenclature of nucleic acid structure parameters. These recommendations result from discussions at an EMBO Workshop on DNA Curvature and Bending held at Churchill College, Cambridge, in September 1988. PMID- 2928109 TI - Codon usage and secondary structure of MS2 phage RNA. AB - MS2 is an RNA bacteriophage (3569 bases). The secondary structure of the RNA has been determined, and is known to play an important role in regulating translation. Paired regions of the genome have a higher G+C content than unpaired regions. It has been suggested that this reflects selection for high G+C content to encourage pairing, but a re-analysis of the data together with computer simulation suggest that it is an automatic consequence in any RNA sequence of the way it folds up to minimise its free energy. It has also been suggested that the three registers in which pairing can occur in a coding region are used differentially to optimise the use of the redundancy of the genetic code, but re analysis of the data shows only weak statistical support for this hypothesis. PMID- 2928108 TI - Oligothymidylates covalently linked to an acridine derivative and with modified phosphodiester backbone: circular dichroism studies of their interactions with complementary sequences. AB - Oligothymidylates involving alternating alkyl phosphotriester-phosphodiester or methylphosphonate-phosphodiester backbones and covalently linked to an acridine derivative have been studied using circular dichroism. Two isomers with the same diastereoisomeric configuration for all the phosphotriesters (ethyl triester and neopentyl triester) or the methylphosphonate linkages were studied. These six compounds were compared to the parent oligonucleotide with unmodified phosphodiester bonds. Intramolecular interactions between the acridine and the bases of the oligonucleotides were revealed by the induced circular dichroism of the acridine dye. Binding to poly(rA) and poly(dA) induced large changes in the circular dichroism signal. All oligothymidylates formed double-stranded complexes with poly(rA). Substitution of phosphotriesters and methylphosphonates to phosphates allowed both double- and triple-stranded structures to be formed with with poly(dA). The double-stranded structures formed with poly(rA) and poly(dA) were characterized by different environments of the acridine dye. The circular dichroism spectra of the complexes with poly(dA) and the thermal stabilities of the complexes formed with both poly(rA) and poly(dA) were drastically dependent of the diastereoisomeric configuration of the phosphate modification. For the complexes formed with the pseudoequatorial stereoisomer the modification of the phosphate groups increased the stability of the complexes as compared with the oligothymidylate containing only phosphodiester linkages whereas it decreased it for pseudoaxial modifications. PMID- 2928110 TI - Anti-OTF-1 antibodies inhibit NFIII stimulation of in vitro adenovirus DNA replication. AB - HeLa cell OTF-1 has been purified on the basis of its DNA binding activity and used to raise a polyclonal rabbit antiserum. This antiserum is shown to recognize both native and denatured OTF-1 from both human and a similar protein from Xenopus culture cells, but to react either more weakly or not at all with the lymphoid cell-specific OTF-2. Separately, NFIII has been purified on the basis of its ability to stimulate Adenovirus DNA replication in vitro. On denaturing polyacrylamide gels OTF-1 and NFIII exhibit identical mobility. Anti-OTF-1 antiserum recognizes NFIII and neutralizes its stimulatory effect on DNA replication. Moreover, OTF-1 can functionally replace NFIII. Taken together with previously published DNA binding data, this indicates that OTF-1 and NFIII are either very closely related or identical. PMID- 2928111 TI - Distinct mouse DNA sequences enable establishment and persistence of plasmid DNA polymers in mouse cells. AB - Distinct elements isolated from mouse genomic DNA confer on plasmid DNA the ability to persist at high copy numbers in mouse L fibroblasts (1). Field inversion gel electrophoresis demonstrated that - in contrast to our previous assumption - the persisting plasmid DNA does not exist extrachromosomally but as clusters of tandem repeats integrated into genomic DNA. Digestion with restriction endonucleases that do not cut within the plasmid DNA results in fragments of 50-300 kb in length indicating reiteration of 10-50 plasmid DNA molecules. Restriction with several enzymes that cut once or twice within the plasmid sequences lead to fragment(s) indicative for head-to-tail tandem repeats. In situ hybridization revealed signals for a long homogeneously staining region (HSR) in one or two chromosomes per cell nucleus. Possibilities how these elements could act in the establishment and/or maintenance of the head-to-tail polymers of plasmid DNA in mouse cells are discussed. PMID- 2928112 TI - Molecular cloning of the cDNA for the human U2 snRNA-specific A' protein. AB - The A' polypeptide is one of the protein constituents of the U2 snRNP particle. A potentially full-length cDNA clone containing the complete coding sequence for this U2 snRNP-specific protein was isolated by screening of a human lambda gt11 expression vector library with an autoimmune anti-(U1,U2)RNP serum. Monospecific antibodies, eluted from the 140-150 kD fusion protein of this cDNA recombinant, specifically recognized the A' protein on immunoblots and immunoprecipitated U2 snRNP particles from nuclear extracts. The identity of the clone was confirmed by in vitro translation of hybrid-selected mRNA or an RNA transcript synthesized from the cDNA insert. RNA blot analysis showed strong hybridization to a single polyadenylated transcript of 1.3 kb in human cells. The nucleotide sequence of the 1054 bp cDNA contains an open reading frame of 756 bp encoding a polypeptide of 255 amino acids with a predicted molecular weight of 28,444 D. The coding sequence is preceded by a 49 bp 5'-untranslated region and followed by a 226 bp 3'-untranslated region containing a single polyadenylation signal. Most striking feature of the deduced primary structure for the A' protein is a leucine-rich region in the amino-terminal half of the polypeptide. In contrast to the other U2 snRNP-specific protein B", the A' protein does not contain segments homologous to the RNP consensus sequences RNP1 and RNP2, common amino acid motifs found in several RNA-binding proteins. In the A' protein, however, the extremely hydrophilic carboxy terminus may constitute an RNA-binding moiety. PMID- 2928113 TI - Structure, expression and regulation of the murine 4F2 heavy chain. AB - The murine 4F2 molecule is a 125 kilodalton disulfide-linked heterodimeric cell surface glycoprotein which has been shown to be involved in the processes of cellular activation and proliferation (1). To elucidate the structure, expression, and regulation of the 4F2 molecule, a murine 4F2 heavy chain (4F2HC) cDNA has been isolated and structurally characterized. The murine 4F2HC is a 526 amino acid (aa) type II membrane glycoprotein which is composed of a 75 aa N terminal intracytoplasmic region, a single hydrophobic putative transmembrane domain, and a 428 aa C-terminal extracellular domain. Comparison with the human 4F2HC cDNA reveals the highest degree of sequence identity within the transmembrane and intracytoplasmic domains. Northern blot analyses have demonstrated that the 4F2HC gene is expressed at relatively high levels in adult testis, lung, brain, kidney, and spleen, and at significantly lower levels in adult liver and cardiac and skeletal muscle. Studies designed to elucidate the pattern of regulation of the murine 4F2HC gene have demonstrated that it is induced during the process of cell activation, but is subsequently expressed at constant levels throughout the cell cycle in exponentially growing cells. PMID- 2928115 TI - The nucleotide sequence of a gene for a putative ribosomal protein S31 of Drosophila. PMID- 2928116 TI - The nucleotide sequence and reading frames of a mutant hepatitis B virus subtype adr. PMID- 2928117 TI - Cloning of the rat adrenal medullary phenylethanolamine-N-methyltransferase. PMID- 2928114 TI - Translation of chloroplast-encoded mRNA: potential initiation and termination signals. AB - A survey of 196 protein-coding chloroplast DNA sequences demonstrated the preference for AUG and UAA codons for initiation and termination of translation, respectively. As in prokaryotes at every nucleotide position from -25 to +25 (AUG is +1 to +3) and for 25 nucleotides 5' and 3' to the termination codon an A or U is predominant, except for C at +5 and G at +22. A Shine-Dalgarno (SD) sequence (GGAGG or tri- or tetranucleotide variant) was found within 100 bp 5' to the AUG codon in 92% of the genes. In 40% of these cases, the location of the SD sequence was similar to that of the consensus for prokaryotes (-12 to -7 5' to AUG), presumed to be optimal for translation initiation. A SD sequence could not be located in 6% of the chloroplast sequences. We propose that mRNA secondary structures may be required for the relocation of a distal SD sequences to within the optimal region (-12 to -7) for initiation of translation. We further suggest that termination at UGA codons in chloroplast genes may occur by a mechanism, involving 16S rRNA secondary structure, which has been proposed for UGA termination in E. coli. PMID- 2928118 TI - Nucleotide sequence of a 17S (18S) rRNA gene from tomato. PMID- 2928119 TI - Mouse thymidine kinase: sequence of a processed pseudogene. PMID- 2928120 TI - Nucleotide sequence of the human liver-type alkaline phosphatase cDNA. PMID- 2928121 TI - Nucleotide sequence of a cDNA encoding bovine brown fat uncoupling protein. Homology with ADP binding site of ADP/ATP carrier. PMID- 2928122 TI - Drosophila virilis Cu-Zn superoxide dismutase gene sequence. PMID- 2928123 TI - Nucleotide sequence of cDNA for rabbit glutathione peroxidase. PMID- 2928124 TI - A Caenorhabditis elegans cDNA that encodes a product resembling the rat glutathione S-transferase P subunit. PMID- 2928125 TI - The nucleotide sequence of bovine tRNA(Ser)UGA gene and its flanking sequences. PMID- 2928126 TI - Amplification of a highly polymorphic VNTR segment by the polymerase chain reaction. PMID- 2928127 TI - Preparation of crude cell extract suitable for amplification of RNA by the polymerase chain reaction. PMID- 2928128 TI - Multiple primer pairs for the detection of HTLV-I by PCR. PMID- 2928129 TI - Quantitative precipitation of short oligonucleotides with low concentrations of cetyltrimethylammonium bromide. PMID- 2928130 TI - The nursing shortage and nursing's legal scope of practice. PMID- 2928131 TI - Regulatory initiatives: instruments for leadership. AB - As this paper has emphasized, regulation of the health professions does not exist in a vacuum. First, regulation of professions and occupations always depends on political circumstances for its inception and operation. Second, regulatory policy issues revolve on questions of value accorded competing issues. In a democracy, values are the province of the public, not of the experts. Nurses can aid the public in sorting out relevant values by taking a leadership role in regulatory initiatives. Third, certain characteristics--expertise, cohesiveness, political salience and leadership--are significant in advancing the policy agenda. The nursing profession must rethink its position on the policy agenda. Fourth, the regulatory pattern of the future outlines an essential role for government--government acting as our agent in accomplishing tasks of social control and social justice. As James Reagan has stated, "Laws inevitably reflect the times in which they were written, expressing social objectives, scientific knowledge and technical capabilities of the era." We can extend that observation to rule making, modes of procedure and legislative patterns. None of these factors is static. Fifth, proposing regulatory initiatives is the cutting edge of practice. In the present social-political-technological environment, only one certainty exists for nursing professionals: The health care field will continue for some time in its present state of flux. Now as never before, nurses have the opportunity to demonstrate leadership, to influence public opinion about health care, and to play an important role in new regulations governing health care and the nursing profession. PMID- 2928133 TI - Nursing, nothing but nursing! PMID- 2928132 TI - Pushing the outside of the envelope. PMID- 2928134 TI - Returning to the roots of the nurse practitioner role. PMID- 2928135 TI - Tort reform. PMID- 2928137 TI - Wild cards in a new health care game. PMID- 2928136 TI - Using the RCT proposal for nursing. PMID- 2928138 TI - Using the public agenda to shape PHN practice. PMID- 2928139 TI - Health care for the homeless. PMID- 2928140 TI - Nursing's response to the challenge of AIDS. PMID- 2928141 TI - Teaching ethics to nursing students. AB - Ethical practice is the responsibility of all nurses. But if they are to understand the principles of ethics and carry them out in their work, nursing curricula must incorporate ethics into course content. Such content requires faculty who understand both ethical theories and their application to nursing. Appropriate methods of evaluating student learning are also needed. The growing complexity of our health care system demands that nurses assume increasing responsibility for ethical decision making. We can no longer ignore the link between ethics and nursing. Ethics education for nurses is mandatory, not elective. PMID- 2928142 TI - Preparing students to shape health policy. PMID- 2928143 TI - State boards and impaired nurses. PMID- 2928144 TI - Organizational integrative mechanisms and adoption of innovations by nurses. AB - The relationship between organizational activities and structures that increase information flow (integrative mechanisms) and nurse adoption of innovations (research results) was studied using Rogers' theory of innovation diffusion. Analysis of variance demonstrated a significant interaction effect between level of integrative mechanism use, institution size, and nurse adoption of innovations. In small hospitals a higher level of integrative mechanism use was related to increased nurse innovation adoption; however, in large hospitals the opposite was found. Of the five categories of integrative mechanisms identified, only Research Conduct and Publication were significantly related to innovation adoption, and then only in small hospitals. In large hospitals, Conference and Presentation, Position and Committee, and Publication categories were demonstrated to be significantly, but negatively, related to innovation adoption among nurses. PMID- 2928145 TI - Tenure and the university reward structure. AB - Reward allocation in selected American universities was investigated using tenure receipt as the most valuable faculty reward. Because American universities are highly stratified organizations, several representative disciplines and an integrative model were used to examine interdisciplinary perceptions of reward criteria. Three hundred sixty six academicians with professional appointments in physics, psychology, sociology, nursing, and management were surveyed by a mailed questionnaire, the Tenure Decision Factor Inventory (TDFI) composed of Achievement (ACH) Ascriptive (ASCRIPT), Internal Political (IP), and External Political (EP) criteria related to tenure receipt. Significant main effects were shown by both discipline and reward criteria. Perceptions of nursing faculty distinguished nursing from the four other study disciplines. Although many factors influenced tenure decisions, the achievement criteria were identified by members of all disciplines as the most important determinants during tenure review. PMID- 2928146 TI - Home visits: effective or obsolete nursing practice? PMID- 2928147 TI - Contextual regression analysis. PMID- 2928148 TI - Insights from "the glorious whitewasher". PMID- 2928149 TI - Urinary bladder and rectal temperature monitoring during clinical hypothermia. AB - Three methods of temperature monitoring were studied in 55 adult hypothermic postcardiac surgery patients using the pulmonary artery, rectum, and urinary bladder as measurement sites. Pulmonary artery temperature served as the standard for core body temperature. Measurements in the rectum were recorded with a disposable plastic temperature probe and in the urinary bladder with a thermistor tipped Foley catheter. Patients were studied within one hour of admission to the cardiac surgical intensive care unit and on an hourly basis until they reached normothermia (37 degrees C). Although mean temperatures did not vary greatly for any group, there was a significant difference between measures over time. Correlations of pulmonary artery and urinary bladder temperatures ranged from .78 to .94, pulmonary artery and rectal temperature from .49 to .82, and urinary bladder and rectal temperature from .46 to .85. The results of this study indicate that the urinary bladder is a reliable indicator of core temperature during rewarming following cardiac surgery. PMID- 2928150 TI - Re: 'Physical Restraint of the Hospitalized Elderly: Perceptions of Patients and Nurses'. PMID- 2928151 TI - Comparison of rectal, axillary, and inguinal temperatures in full-term newborn infants. AB - Rectal, axillary, and inguinal temperatures were compared in 120 full-term infants aged 12 to 48 hours. Thermometers were placed in randomized sequential order and temperatures were recorded every 30 seconds until the reading remained constant for 90 seconds (stabilization). At least 95% of subjects reached temperature stabilization at all sites by 5 1/2 minutes. Mean difference between axillary and inguinal readings was 0.6 degrees F; between rectal and inguinal readings, 0.8 degrees F; and between rectal and axillary 0.2 degrees F. Although the greatest difference between mean temperature readings was found between the rectal and inguinal sites (0.8 degrees F), this pair of readings also had the highest correlation. This finding indicates that inguinal site temperatures are more reflective of rectal temperatures and may be less sensitive to effects of brown adipose tissue heat generation. PMID- 2928152 TI - A causal model of positive health practices: the relationship between approach and replication. AB - This study supports the position that causal models developed a priori preclude replication with varied samples. Based on a critique of a study of positive health practices among adults (Muhlenkamp & Sayles, 1986), a causal model of positive health practices for adolescents was developed a priori from a theoretical formulation. Using data from a sample of 165 adolescents who responded to the Personal Lifestyle Questionnaire, the Rosenberg Self-Esteem Scale, Part 2 of the Personal Resource Questionnaire which measures a social support system, and a demographic data sheet, the intercorrelations among the study variables were analyzed using correlation coefficients. The causal model was then tested with the adolescent data using the LISREL VI program. The results showed a relatively good fit of the model to the data via a number of indicators. The model was then applied to data published from adults (Muhlenkamp & Sayles) using the LISREL VI program. The results indicated that there was a relatively poor fit of the model to the adult data, thus demonstrating the problem of replicating causal models with varied samples when the correct approach to causal modeling is used. The discussion focuses on theoretical and methodological reasons for the findings. PMID- 2928153 TI - Family caregiving for a relative with Alzheimer's dementia: coping with negative choices. AB - The constant comparative method was used to generate a grounded theory explicating the process of family caregiving for a relative with Alzheimer's dementia. Findings from 20 in-depth, face-to-face interviews conducted with a purposive sample of family caregivers in their homes revealed that much of the caregiving experience consists of coping with negative choices wherein all possible alternatives are undesirable. The three stages of Surviving on the Brink, (1) Taking it on, (2) Going through it, and (3) Turning it over, capture the variation in behavior. Continued validation of this process of coping and decision making offers promise for substantive theory development on which nursing intervention programs for easing caregiver burdens might be based. PMID- 2928154 TI - A test of the health promotion model with blue collar workers. AB - The health promotion model (Pender, 1987b) was tested with a volunteer sample of 179 blue-collar workers. Four psychological variables (importance of health, perceived health locus of control, health status, and self-efficacy), one modifying variable (selected demographics), and certain health-promoting behaviors were examined. Pearson product moment correlations and stepwise and hierarchical multiple regression techniques were used to analyze the data. Each of the psychological variables examined was predictive of health-promotive behaviors. Health status and self-efficacy were the most powerful predictors. The modifer role of demographics was also supported. The results suggest the health promotion model is potentially useful for explaining the occurrence of health promotive behaviors among blue-collar workers. PMID- 2928155 TI - Taken to task. Interview by Jane Feinmann. PMID- 2928156 TI - Supplementary questions. PMID- 2928157 TI - Shifting boundaries. PMID- 2928158 TI - Life crises. Realities of Cleveland. PMID- 2928159 TI - Acoustic neuroma. PMID- 2928160 TI - Break out! PMID- 2928161 TI - Time for talk. PMID- 2928162 TI - NHS Review. Storm clouds ahead? PMID- 2928163 TI - Gift horse or Trojan horse? PMID- 2928164 TI - Death with dignity: Baha'i faith. PMID- 2928165 TI - Code of Conduct. The whistle blower. PMID- 2928166 TI - Quest. Thoughts on a new curriculum. PMID- 2928167 TI - Held without help. PMID- 2928168 TI - An isolating experience. PMID- 2928169 TI - Crash landing. PMID- 2928170 TI - Kenneth's conundrum. PMID- 2928172 TI - Head injury. Back from the edge. PMID- 2928171 TI - Head injury. Early rehabilitation of head-injured patients. PMID- 2928173 TI - Head injury. The forgotten injury. PMID- 2928174 TI - Pressure prevents nausea. PMID- 2928175 TI - Kawasaki syndrome. PMID- 2928176 TI - Effects of anaesthesia on mental performance in the elderly. AB - It has been known for a long time that mental impairment may occur in elderly patients following surgery and this has been attributed to anaesthesia. However, until recently, little systematic research has been carried out in this area. One problem has been that many factors apart from anaesthesia influence the mental function of elderly surgical patients. This paper describes a study in progress which is attempting to isolate the effects of anaesthesia per se on mental function, and identify which aspect of anaesthesia may be responsible. Results from the study indicate that advanced age itself does not predispose to marked postoperative impairment of reaction time, but they do support the idea that patients with some pre-operative mental impairment may be vulnerable to effects of anaesthesia. Thus it appears that the biological age of the brain rather than its chronological age may influence vulnerability to anaesthesia. PMID- 2928177 TI - Understanding mourning. PMID- 2928178 TI - Method in their madness. PMID- 2928179 TI - Code of conduct. Cruelty and neglect. PMID- 2928180 TI - Do you care enough to serve? PMID- 2928181 TI - Spotlight on children. PMID- 2928182 TI - Spotlight on children. A family friend. PMID- 2928183 TI - When care has to be rationed. PMID- 2928184 TI - A chilling business? PMID- 2928185 TI - Blind justice. PMID- 2928186 TI - Sexuality. An uninvited guest. PMID- 2928187 TI - Sexuality and the ostomist. PMID- 2928188 TI - Fishing in deeper waters. PMID- 2928189 TI - Arthritis: social problems and practical solutions. PMID- 2928190 TI - This one will run and run. PMID- 2928191 TI - Slow steps towards success. PMID- 2928193 TI - Ring-a-ring o'roses. PMID- 2928192 TI - Making sense of bowel preparations for diagnostic procedures. PMID- 2928194 TI - Death with dignity: Islam. PMID- 2928195 TI - Computers in Nursing News. PMID- 2928197 TI - Computers in Nursing News. Midwives take control. PMID- 2928196 TI - Computers in Nursing News. The double-edged sword. PMID- 2928198 TI - When matron ruled the hospital. PMID- 2928199 TI - Focus on the NHS Review. PMID- 2928200 TI - NHS Review. Clarke on the Review. PMID- 2928201 TI - NHS Review. Clay on the Review. PMID- 2928202 TI - Hidden intent. PMID- 2928203 TI - Care of the elderly. Patient first? PMID- 2928204 TI - Care of the elderly. Times past. PMID- 2928205 TI - Sexuality. Promoting fulfillment. PMID- 2928206 TI - Taking the fear out of A & E. PMID- 2928207 TI - Prepare for project 2000. PMID- 2928208 TI - Who will speak for me? PMID- 2928209 TI - Death with dignity. Hinduism. PMID- 2928210 TI - Polycystic kidney disease. PMID- 2928211 TI - When all comes to nought. PMID- 2928212 TI - Systems of life. No. 168. Senior systems. 33. Hypothermia. PMID- 2928213 TI - Midwives' Journal. PMID- 2928214 TI - Midwives' Journal. Antenatal care. PMID- 2928215 TI - Midwives' Journal. HIV and pregnancy. PMID- 2928216 TI - Midwives' Journal. Working without registrars. PMID- 2928217 TI - The Cook report. Interview by Andrew Cole. PMID- 2928218 TI - Unconditional discharge? PMID- 2928219 TI - Marathon man. Interview by Martin Vousden. PMID- 2928220 TI - Education. Who is the support worker? PMID- 2928221 TI - Education. More questions than answers. Interview by Claire Laurent. PMID- 2928222 TI - Education. Short cut or short change? PMID- 2928223 TI - Education. View from the frontline. PMID- 2928224 TI - NHS Review. Signalling a new direction. PMID- 2928225 TI - Pain control and hypnosis. PMID- 2928226 TI - All together now. PMID- 2928227 TI - China's long march to health. PMID- 2928229 TI - Rights and wrongs. PMID- 2928230 TI - Continence. PMID- 2928228 TI - Death with dignity: Sikhism. PMID- 2928231 TI - Continence. Are you sitting comfortably? PMID- 2928232 TI - Continence. Co-ordinating continence care. PMID- 2928233 TI - The unknown addicts. PMID- 2928234 TI - The hidden agenda. PMID- 2928235 TI - The headless chicken syndrome. PMID- 2928237 TI - The killing fields. PMID- 2928236 TI - Partners in care. PMID- 2928238 TI - NHS Review. What's in it for us? PMID- 2928239 TI - Making the service suit the patient. PMID- 2928240 TI - Education. Support workers: helper or hindrance? PMID- 2928241 TI - Education. Support workers: support--no supplant. PMID- 2928243 TI - Death with dignity: Judaism. PMID- 2928242 TI - Health at Heathrow. PMID- 2928244 TI - Mental Health: the journal for psychiatric nurses. PMID- 2928245 TI - Mental Health. Fads and fashions. PMID- 2928246 TI - Mental health. Tea for three. PMID- 2928247 TI - Red alert. PMID- 2928248 TI - Weighted against care? PMID- 2928249 TI - Looking to the long-term. PMID- 2928250 TI - Sneak or saviour? PMID- 2928251 TI - Life crises. Breakdown of a family. PMID- 2928252 TI - Life crises. When a baby dies. PMID- 2928254 TI - Death with dignity: Buddhism. PMID- 2928253 TI - Services for the dying. PMID- 2928255 TI - Parental involvement in intravenous therapy. PMID- 2928256 TI - Resettlement of long-stay psychiatric patients. AB - A follow-up study of patients from two long-stay psychiatric hospitals in East Yorkshire health authority looked at a sample of patients who had been discharged into the community and a sample within the institution. The study looked particularly at the quality of life of patients who had been discharged and at any differences between them and patients still living in the institution. PMID- 2928257 TI - NHS Review. Opportunity knocks. PMID- 2928258 TI - Making sense of endoscopic retrograde cholangiopancreatography. PMID- 2928259 TI - The needs for a normal life. PMID- 2928260 TI - The Journal of Infection Control Nursing. PMID- 2928261 TI - The Journal of Infection Control Nursing. Sterilisation in GP surgeries. PMID- 2928262 TI - What's all this fuss about image? PMID- 2928263 TI - DMSO and extravasation of mitomycin. PMID- 2928264 TI - Alopecia article well received. PMID- 2928265 TI - Mandatory AIDS education. PMID- 2928266 TI - AIDS research: moving beyond basic biology. PMID- 2928267 TI - Inter-agency collaboration: teaching breast self-examination to black women. AB - Excessive breast cancer mortality and limited use of mammography among black women point to a need for breast cancer education and increased use of breast self-examination (BSE) and other screening procedures. The Illinois Cancer Council (ICC), a consortial comprehensive cancer center, and the Chicago Chapter of the National Black Nurses' Association (CCNBNA) developed and piloted an educational project to increase black women's knowledge about breast cancer and their use of BSE and other screening methods. This paper describes the steps leading up to this collaborative effort, the procedures necessary to implement it, the difficulties encountered, and the impact of the educational program on the CCNBNA nurses and the high risk, hard-to-reach, underserved women who participated. This program is offered as a model for a collaborative effort between a cancer center or other healthcare facility and a professional organization to address unmet community health needs. PMID- 2928268 TI - Developing a breast cancer screening program for Chinese-American women. AB - The Chinese, like other minority groups, often underuse cancer screening services because of language, cultural, and economic barriers. Nonattendance reduces the probability that cancer will be detected in its earliest and often most curable form. To improve use of cancer screening services among Chinese-Americans, a community-based coalition organized a one-day demonstration cancer awareness and screening program--the Breast Cancer Screening Day for Chinese Women. More than 100 women, many of whom did not speak English, attended the program. Six abnormal mammograms required follow-up and one breast cancer was detected. The planning process used to develop this successful project is described as are suggestions to improve future screening programs for ethnic minorities. PMID- 2928269 TI - Cigarette craving and subsequent coping responses among smoking cessation clinic participants. AB - Withdrawal symptoms, including craving, have been cited as common reasons for relapse into smoking. This study looked at 29 subjects enrolled in a community based smoking cessation clinic to determine their levels of craving at 48 hours and end-of-clinic, as well as to determine those situational factors that precipitated a craving episode and the subsequent coping responses used during the first 48 hours post-cessation. Subjects completed the Shiffman-Jarvik Craving Subscale (SJCS) and the Visual Analogue Scale of Craving (VAS) to measure the severity of their cigarette craving. Data obtained from both tools were analyzed via paired t-tests. Mean difference scores on the SJCS (D = 1.42, t = 4.58, p less than 0.0002) and the VAS (D = 36.39, t = 4.46, P less than 0.0003) indicated that all subjects experienced craving during the first 48 hours after quitting, and that craving decreased significantly over a two-week period, corresponding with the end-of-clinic. Situational factors related to craving included: being at work, negative affect, and late afternoon hours. Coping responses to craving were categorized as either affective- or problem-oriented, with the former cited by subjects 73% of the time. PMID- 2928271 TI - Nurses' perceptions of their pain assessment skills, pain management practices, and attitudes toward pain. AB - Nursing pain assessments are influenced by the length of available tools, patient characteristics, patient pathology, concern about addictive behavior, and characteristics of the nurse. The relationship among these variables was explored in a sample of community hospital nurses (N = 59) and ONS members (N = 19). Although a number of interesting similarities were found in the two groups, age, professional and continuing education, and care setting appear to be related to differences in pain assessment practices. Implications for practice, research, and education include teaching nurses to: assess factors related to quality of life in the pain experience, assess and validate data from families, assess coping skills, and teach patients to use behavioral pain management strategies. The findings also suggest that further study is needed concerning the relationship between personal beliefs and experiences and the assessment and management of pain. Membership in professional organizations appears to be associated with comprehensive approaches to the assessment and management of cancer pain and should be addressed in further research. PMID- 2928270 TI - Effects of fluid manipulation on the incidence of vomiting during outpatient cisplatin infusion. AB - The influence of fluid intake and hydration rate on the frequency of vomiting was evaluated during 254 outpatient cisplatin infusions administered to 60 patients. The basic antiemetic regimen was consistent and used metoclopramide hydrochloride (Reglan) 2 mg/kg/dose (means = 150 mg) starting 30 minutes before cisplatin for a total of three doses; dexamethasone (Decadron) mean - 15 mg - and lorazepam (Ativan) 1 mg intravenous bolus before cisplatin, along with thiethlperazine maleate (Torecan) given routinely throughout the treatment beginning the evening before. Only 20% (38/192) of patients experienced symptoms of vomiting when hydrated at a rate of greater than 333 cc/hour as opposed to 44% (27/62) patients hydrated at a rate of 300 cc/hour or less (p = 0.01). Patients whose oral intake ranged from 400 cc to 1000 cc experienced noticeably less vomiting (14%) than patients who either refused fluids (39%, p = 0.001) or exceeded 1000 cc oral intake (36%, p less than 0.05) during treatment. Manipulation of total fluid intake (IV plus oral), although not statistically significant, seemed to affect the incidence of vomiting. By maintaining a positive intake/output ratio greater than 1, patients were able to decrease their vomiting episodes. Patients who gained weight during the treatment experienced significantly fewer episodes of vomiting (29%) than those who either lost or maintained their weight (71%). Findings suggest that manipulating both oral and IV fluid intake as well as the IV fluid rate may reduce symptoms of vomiting in the outpatient cisplatin setting. PMID- 2928272 TI - The relationship between age and intensity of cancer-related symptoms. AB - Nausea, vomiting, and pain are among the most universally feared problems associated with cancer and its treatment. However, not all individuals experience these symptoms, and intensity varies widely for those who do. A number of variables might affect intensity of nausea, vomiting, and pain. This study explored the relationship between age and intensity of cancer-related nausea, vomiting, and pain. The study included a sample of 99 subjects who were experiencing pain and a sample of 25 subjects at risk for chemotherapy-induced nausea and vomiting. An independent t-test revealed a significant difference in intensity of symptoms between younger and older subjects for the pain group (p less than 0.01); the Mann-Whitney U revealed a significant difference by age in the nausea and vomiting group (p less than 0.05). In addition, there were low to moderately negative relationships found between age and symptom intensity for both groups (pain, r = -0.22, p less than 0.05; nausea and vomiting, r = -0.43, p less than 0.05). Results support the commonly held belief that elderly people report a lower intensity of some physical symptoms than do younger individuals. However, relationships between age and symptom intensity are weak, which suggests that individuals' responses to cancer-related symptoms should continue to be the nurse's primary concern. PMID- 2928273 TI - Teaching patients to care for drains after breast surgery for malignancy. AB - The early discharge program exemplifies interdisciplinary collaboration. Teaching patients to care for their drains not only results in a decreased length of stay and potential cost savings, but also allows patients to recuperate at home with their families. PMID- 2928274 TI - Cocaine withdrawal. An effective three-drug regimen. PMID- 2928275 TI - Glut reaction. PMID- 2928276 TI - How to stay out of jail (by not breaking antitrust laws) PMID- 2928278 TI - What you won't see if you don't look. PMID- 2928277 TI - Differential diagnosis of psychosis. A brief guide for the primary care physician. AB - By keeping in mind that not a psychosis is schizophrenia, the primary care physician can often avoid misdiagnosis in behaviorally disturbed patients. Abnormal behavior may result from mood disorders, drug-induced psychosis and other organic disorders, personality disorders, delusional disorders, autism, or mental retardation. A long-term history is essential for correct diagnosis and treatment. PMID- 2928279 TI - Intestinal infections in patients with AIDS. AB - A broad spectrum of gastrointestinal pathogens can cause diarrhea in patients with acquired immunodeficiency syndrome (AIDS). A systematic approach utilizing symptomatology and the appropriate diagnostic tests will maximize the clinician's chance of identifying the specific pathogens. Enteric infections in AIDS patients are often incurable and require prolonged therapy and chronic suppression. Experimental agents show promise of decreasing the morbidity and mortality attendant on diarrhea in AIDS patients. PMID- 2928280 TI - Electromyography in the diagnosis of sciatica. PMID- 2928281 TI - Vitamin A toxicity presenting as jaundice. PMID- 2928282 TI - Estrogen replacement after menopause. When is it warranted? AB - As longevity increases, so will the number of women living for many years beyond menopause. The estrogen deprivation that occurs at menopause results in many degenerative changes in a woman's body, some of which cause unpleasant or disabling symptoms. To maintain good health and vitality in menopausal and postmenopausal women, serious consideration should be given to appropriate estrogen replacement therapy. Although such therapy has some risks, the benefits appear to exceed the risks. PMID- 2928284 TI - Neurologic aspects of the abused child syndrome. PMID- 2928283 TI - Is it really a fungal infection? PMID- 2928285 TI - Joint pain in children. When is it serious? AB - Diagnosis of the cause of joint pain in children depends on the physician's ability to distinguish benign from more serious joint conditions. Benign conditions include trauma, overuse syndromes, hypermobility syndrome, chondromalacia patellae, benign recurrent limb pains, and psychogenic rheumatism. Conditions that require further evaluation and ongoing therapy include Lyme disease, rheumatic fever, juvenile rheumatoid arthritis, neoplastic disease, various orthopedic conditions, infection, seronegative spondyloarthropathies, and the rarer connective tissue diseases. If diagnosed early and treated appropriately, most joint problems of childhood have a very good prognosis. PMID- 2928287 TI - 'Don't worry, insurance will cover it!' This attitude is destroying the economy. PMID- 2928286 TI - Borderline personality disorder. When medical care is complicated by mental illness. AB - Management of patients with borderline personality disorder on a medical ward requires the cooperation of all caregivers involved. First, it is necessary to recognize the disorder in patients who exhibit maladaptive behavior. Next, a comprehensive plan of behavioral management should be implemented that includes (1) clear communication among staff members, (2) education of staff members, (3) a consistent approach to the patient, (4) firm limits on the patient's behavior, and (5) an empathic rather than confrontational response to the patient's demands. Use of psychoactive medications may be a valuable adjunct to these approaches. A consulting psychiatrist can confirm the diagnosis and help to develop and implement the management plan. PMID- 2928288 TI - Is this child's fever a worry? PMID- 2928289 TI - Finding the cause of postoperative fever. PMID- 2928291 TI - Medicine is changing. PMID- 2928290 TI - Cuts and scrapes of knees and elbows. AB - Knee and elbow injuries are seen frequently by the primary care physician and require prompt and careful treatment in order to prevent infection, preserve joint function, and avoid scarring. A thorough history and physical examination help to rule out more significant damage to the related joint, nerves, or tendons. Immobilization of the joint may be necessary to prevent dehiscence, and the patient should be instructed to return for further examination if signs of infection develop. PMID- 2928292 TI - The malpractice mess. PMID- 2928293 TI - Free needles: a public health hazard. PMID- 2928294 TI - Chemical dependency. What to do once you suspect it. AB - Chemical dependency is a serious but treatable disease frequently encountered in primary care. By carefully gathering as much data as possible, the physician can successfully intervene and help the patient and family begin a program of recovery. In the case of a resistant patient, formal intervention can facilitate breaking through the wall of denial. As a last resort, commitment to a treatment program is also an option in many states. If a patient steadfastly refuses to admit that he or she has a problem with alcohol or other drugs, the physician should continue to care for the patient and to help his or her family members find a recovery program for themselves. PMID- 2928295 TI - Polarity as a criterion in protein design. AB - Hypothetical proteins can be tested computationally by determining whether or not the designed sequence-structure pair has the characteristics of a typical globular protein. We have developed such a test by deriving quantities with approximately constant value for all globular proteins, based on empirical analysis of the exposed and buried surfaces of 128 structurally known proteins. The characteristic quantities that best appear to segregate badly designed or deliberately misfolded proteins from their properly folded natural relatives are the polar fraction of side chains on the protein surface and, independently, in the protein interior. Three of the seven hypothetical structures tested here can be rejected as having too many polar side-chain groups in the interior or too few on the protein surface. In addition, a recently designed nutritional protein is identified as being very much unlike globular proteins. These database-derived characteristic quantities are useful in screening designed proteins prior to experiment and may be useful in screening experimentally determined (X-ray, NMR) protein structures for possible errors. PMID- 2928296 TI - Modelling the polypeptide backbone with 'spare parts' from known protein structures. AB - An automatic procedure for building a protein polyalanine backbone from C alpha positions and 'spare parts' retrieved from a data base of 66 high-resolution protein structures is described. Protein backbones are constructed from overlapping fragments of variable length, which allows the backbone of regular secondary structure elements to be built in one block. The procedure is shown to yield backbones which compare very favourably with those from highly refined X ray structures (r.m.s. deviation between generated and crystal structures less than 1A). The method is furthermore quite insensitive to experimental errors in C alpha positions as well as to the size of the data base, and is seen to yield valuable insight into the relationships between sequence and 3-D structure: one example on triose phosphate isomerase, a beta-barrel protein, shows that beta alpha loops can be considered as structurally more uncommon than alpha beta loops. The 'spare parts' approach is also found to be useful for general-purpose modelling of local structural changes produced by insertion or deletion of residues. It should, however, be used with caution. Crude selection criteria based solely on fragment length and geometric fit to the loop base regions yield realistic backbones in about two-thirds of the test cases (r.m.s. deviations from refined crystal structure approximately 1A). In the remaining cases, sequence information, in particular the presence of glycine residues which tend to adopt more unusual backbone conformations, must be considered to obtain comparable results. PMID- 2928297 TI - Alignment of protein sequences using the hydrophobic core scores. AB - Making an alignment of the amino acid sequences is an essential step in the prediction of an unknown protein structure by model building from the known structure of a protein of the same family. To improve the accuracy of the alignments, we introduced the concept of hydrophobic core scores, which restrains putting insertions/deletions in the hydrophobic core regions of the protein. Eight pairs of protein sequences were aligned by this method, and the quality of the alignments were assessed by reference to those obtained by the structural superposition. The introduction of the hydrophobic core scores derived from the knowledge of the tertiary structure of one of each pair resulted in an improvement of the accuracy of the alignments. The quality of the alignment was found to depend on the homology of the protein sequences. PMID- 2928298 TI - Selective proton labelling of amino acids in deuterated bovine calbindin D9K. A way to simplify 1H-NMR spectra. AB - A technique for proton labelling of selected amino acids in deuterated calbindin D9K, heterologously expressed in E. coli, was developed in order to simplify and obtain higher resolution in 1H-NMR spectra. The spectra from two double-labelling experiments, Val plus Ser and Val plus Leu, when compared to the uniformly protonated protein showed a dramatically simpler pattern with low background signals and gave considerably sharper resonances due to reduced relaxation rates in the deuterated proteins. The selective proton labelling technique will enable detailed and rapid analysis of interesting domains of proteins and will also make the analysis of larger proteins feasible. PMID- 2928299 TI - Chemical synthesis, expression and product assessment of a gene coding for biologically active human tumour necrosis factor alpha. AB - A gene encoding human tumour necrosis factor alpha (TNF-alpha) has been chemically synthesized, cloned and expressed to yield a biologically active protein in Escherichia coli. The 480-bp gene was assembled by enzymic ligation of 32 oligonucleotides, cloned directly into M13mp18 for sequence verification and expressed in the broad host range high-level expression vector pMMB66EHST. Expressed recombinant TNF-alpha was shown to have the correct molecular weight, processed N-terminal sequence, antibody cross-reactivity and tumour cell killing activity. The expression product of the synthetic gene has been purified to homogeneity by a two-step ion-exchange procedure and the purified material shown to be active. PMID- 2928300 TI - Optical imaging of the spatial distribution of beta-particles emerging from surfaces. AB - The multiplication in gases of ionization electrons, by the effect of the electric fields between parallel electrodes, leads to the emission of light from the molecules excited in the avalanche process. The optical imaging of this light, with intensifiers, on charge-coupled devices permits the localization, in the gaseous volume, of the entrance points of the beta-particles emitted by radioactive compounds placed close to or at the cathode electrode. Thin slices of anatomical samples labeled with 3H show detailed structures 30 microns in size. Gels carrying 32P or 35S are imaged with accuracies of the order of 0.5 mm (full width at half maximum). In comparison with photographic emulsion, the gain in time for data taking is close to a factor of 100, with the advantage of linearity and wider dynamic range in the intensity measurement and a greatly improved signal-to-noise ratio. PMID- 2928301 TI - Brain protein kinase C phosphorylating poly(arginine,serine) or lamin B is stimulated by anions and by an activator purified from bovine serum albumin preparations. AB - The phosphorylation of histone by purified protein kinase C (PK-C) from rat brain is dependent on the presence of Ca2+ and lipids. Phosphorylation of a synthetic random polymer of arginine and serine (3:1) is only moderately enhanced by Ca2+ and lipids, but it is greatly enhanced in the absence of Ca2+ and lipids by a contaminant in crystalline bovine serum albumin or by heated cellular fractions. The phosphorylation ratio of histone to poly(arginine,serine) varies between different PK-C fractions from brains of rat, pig, or lamb. These variations are partly caused by a PK-C isozyme that prefers poly(arginine,serine) over histone as substrate. The kinase activator (KA) was partly purified from bovine serum albumin and from extracts of plasma membranes of human placenta. KA is also present in mitochondria, nuclei, and the cytosol. Sulfates and phosphates at 10 mM substitute for KA with poly(arginine,serine) as substrate. The phosphorylation of histone III in the presence of Ca2+ and lipids is moderately stimulated by KA, but the phosphorylation of lamin B and some other endogenous proteins is greatly enhanced by KA. With histones as substrates, inorganic anions do not stimulate phosphorylation. The phosphorylation of poly-(arginine,serine) is very sensitive to low concentrations of staurosporin and is inhibited by PK-C antibody, but, in contrast to histone phosphorylation, it is resistant to sphingosine and polymyxin B. The poly(arginine,serine) phosphorylating activity is more stable at 4 degrees C than the histone phosphorylating activity, but the latter is stabilized by 0.05% Triton X-100. PMID- 2928302 TI - Reconstitution of Golgi vesicle CMP-sialic acid and adenosine 3'-phosphate 5' phosphosulfate transport into proteoliposomes. AB - We have previously shown that Golgi apparatus vesicles transport nucleotide sugars and nucleotide sulfate into their lumen. These transport activities are organelle and substrate specific and are characterized by apparent Km for nucleotide derivatives in the low micromolar range. As part of our goal of purifying and characterizing the above transport proteins, we have reconstituted a protein extract from rat liver Golgi membranes into phosphatidylcholine liposomes. The resulting proteoliposomes transport CMP-N-acetylneuraminic acid (CMP-AcNeu) and adenosine 3'-phosphate 5'-phosphosulfate with very similar affinity and inhibition characteristics as intact Golgi vesicles. Sialic acid and sodium sulfate, which are transported only very slowly into the lumen of Golgi vesicles, are transported at low rates by the reconstituted proteoliposomes. Neither rough endoplasmic reticulum-derived vesicles nor proteoliposomes made from proteins of the rough endoplasmic reticulum transport CMP-AcNeu. The above results demonstrate that this reconstituted system can be used for further purification and characterization of nucleotide sugar and nucleotide sulfate translocator proteins. This approach should also be useful to study membrane transport proteins of lysosomes and endosomes. PMID- 2928303 TI - Multiple post-transcriptional regulatory mechanisms in ferritin gene expression. AB - We have investigated the mechanisms involved in the regulation of ferritin biosynthesis in K562 human erythroleukemia cells during prolonged exposure to iron. We show that, upon addition of hemin (an efficient iron donor) to the cell culture, the rate of ferritin biosynthesis reaches a maximum after a few hours and then decreases. During a 24-hr incubation with the iron donor the concentrations of total ferritin heavy (H) and light (L) subunit mRNAs rise 2- to 5-fold and 2- to 3-fold, respectively, over the control values, while the amount of the protein increases 10- to 30-fold. The hemin-induced increment in ferritin subunit mRNA is not prevented by deferoxamine, suggesting that it is not directly mediated by chelatable iron. In vitro nuclear transcription analyses performed on nuclei isolated from control cells and cells grown in the presence of hemin indicate that the rates of synthesis of H- and L-subunit mRNAs remain constant. We conclude that iron-induced ferritin biosynthesis is governed by multiple post transcriptional regulatory mechanisms. We propose that exposure of cells to iron leads to stabilization of ferritin mRNAs, in addition to activation and translation of stored H- and L-subunit mRNAs. PMID- 2928304 TI - Crystal lattice packing is important in determining the bend of a DNA dodecamer containing an adenine tract. AB - The crystal structure of a DNA duplex dodecamer d(CGCAAAAATGCG) and its complementary strand has been determined at 2.6-A resolution. Although our goal was to deduce the structural features of the static bending of the helical axis exhibited by adenine-tract structures in solution, we conclude that the overall bend of 20 degrees in the direction of the major groove observed here arises from the forces associated with crystal packing. An isomorphous dodecamer brominated on one strand provides experimental evidence that this asymmetric sequence is positioned in two orientations in the crystal lattice that are related by a 180 degrees rotation around the pseudodyad axis of the sequence. The bend in these two differently positioned DNA molecules depends on their orientation in the crystal, not on their sequence. As with previously determined structures containing adenine tracts, the adenine and thymine base pairs are highly propeller twisted. The N-6 of the adenine comes within hydrogen bonding distance of the O-4 of thymine one step down the helix, facilitating the formation of a series of bifurcated hydrogen bonds within the adenine tract. The adenine tract is relatively straight and the bending is localized outside this region. PMID- 2928305 TI - Biological photocathodes. AB - Biological surfaces emit electrons when subjected to UV light. This emission is increased greatly after exposure to cesium vapor. Increases from 2 to 3 orders of magnitude are observed, depending on the biochemicals present. Heme and chlorophyll exhibit unusually high photoemission currents, which are increased further after cesiation. Photoemission from proteins and lipids is much less but also is increased by exposure to cesium. The formation of photocathodes with cesium greatly increases the practical magnifications attainable in photoelectron microscopy of organic and biological specimens. Photoelectron micrographs taken at magnifications greater than or equal to X 100,000 of chlorophyll-rich thylakoid membranes and of colloidal gold-labeled cytoskeleton preparations of cultured epithelial cells demonstrate the improvement in magnification. The selectivity and stability of the photocathodes suggest the possibility of detecting chromophore binding proteins in membranes and the design of photoelectron labels for tagging specific sites on biological surfaces. PMID- 2928306 TI - Complete nucleotide sequence of a molecular clone of woodchuck hepatitis virus that is infectious in the natural host. AB - Woodchuck hepatitis virus (WHV) DNA was cloned from viral particles obtained from the serum of a woodchuck with a naturally acquired infection. The complete nucleotide sequence of the virus genome was determined and found to be 3323 base pairs long. Transfection experiments demonstrated that the recombinant WHV DNA was infectious in each of 18 woodchucks tested and established a chronic carrier state in 1 of 13 neonates and 3 of 5 adult animals. WHV DNA from serum particles from the chronically infected neonate was cloned and the nucleotide sequence of three independent recombinants was compared directly with that of the input recombinant DNA. The consensus sequence of the three progeny genomes was identical to that of the parental DNA sequence. Therefore, transfection of woodchuck livers with recombinant WHV DNA induces active virus replication and gene expression and yields progeny genomes that are faithful copies of the input virus genome. PMID- 2928307 TI - Post-translational modifications in the large subunit of ribulose bisphosphate carboxylase/oxygenase. AB - Two adjacent N-terminal tryptic peptides of the large subunit of ribulose bisphosphate carboxylase/oxygenase [3-phospho-D-glycerate carboxy-lyase (dimerizing), EC 4.1.1.39] from spinach, wheat, tobacco, and muskmelon were removed by limited tryptic proteolysis. Characterization by peptide sequencing, amino acid composition, and tandem mass spectrometry revealed that the N-terminal residue from the large subunit of the enzyme from each plant species was acetylated proline. The sequence of the penultimate N-terminal tryptic peptide from the large subunit of the spinach and wheat enzyme was consistent with previous primary structure determinations. However, the penultimate N-terminal peptide from the large subunit of both the tobacco and muskmelon enzymes, while identical, differed from the corresponding peptide from spinach and wheat by containing a trimethyllysyl residue at position 14. Thus, tryptic proteolysis occurred at lysine-18 rather than lysine-14 as with the spinach and wheat enzymes. A comparison of the DNA sequences for the large subunit of ribulose bisphosphate carboxylase/oxygenase indicates that the N terminus has been post translationally processed by removal of methionine-1 and serine-2 followed by acetylation of proline-3. In addition, for the enzyme from tobacco and muskmelon a third post-translational modification occurs at lysine-14 in the form of N epsilon-trimethylation. PMID- 2928308 TI - Evidence for the progressive and adaptive nature of spontaneous transformation in the NIH 3T3 cell line. AB - The NIH 3T3 mouse cell line is widely used as a recipient of DNA from tumors to demonstrate the presence of transforming oncogenes. We show that these cells produce transformed foci spontaneously if kept in the confluent state for more than 10 days. The formation of foci depends on the type and concentration of bovine serum used in the medium and passage history of the cells. Cells maintained in continuous exponential multiplication in the subconfluent state by transfer every 2-3 days in medium with 10% calf serum failed to develop the capacity to produce foci in 2% calf serum, but those transferred the same way in 2% calf serum or in 10% fetal bovine serum, which is a less potent growth stimulant, did develop that capacity to an increasing degree over time. The number of transformed cells increased sharply with the time that a culture remained in the confluent state. There are several morphological types and degrees of transformation, which indicates that the underlying changes are varied and the process is progressive. The results also suggest that transformation occurs in a fraction of an entire cell population that is undergoing a physiological adaptation to moderate constraints on its growth. PMID- 2928310 TI - Quantitative imaging of free and total intracellular calcium in cultured cells. AB - Techniques of fluorescence and ion microscopies were combined to study the free [Ca2+] and total Ca in NIH 3T3 fibroblast and L6 rat myoblast cells. Free Ca2+ measurements with the Ca2+ indicator fura-2 and digital imaging reveal an inhomogeneous distribution of free cytoplasmic Ca2+ in both cell lines. Fura-2 also reveals a difference in free Ca2+ activity between the nucleus and cytoplasm of cells. Ion microscopic observations on sister cells show that total Ca in the cytoplasm is also inhomogeneously distributed and that mean cytoplasmic levels of total Ca are higher than levels in the nuclei. In the nuclei of NIH 3T3 cells, the mean free [Ca2+] and total [Ca] were 110 +/- 30 nM and 225 +/- 43 microM, respectively, while regions in the cell cytoplasm contained up to 490 +/- 270 nM free [Ca2+] and 559 +/- 184 microM mean total [Ca]. Intracellular total Ca was greater than 3 orders of magnitude higher than intracellular free Ca2+ in either nuclear or cytoplasmic compartments. Perinuclear cytoplasmic regions in 3T3 cells contained higher free and total Ca than the cell nucleus. Loading of cells with fura-2 did not modify the subcellular distribution of total K, Na, Ca, or Mg. This combination of two powerful ion imaging techniques provides a comparison between free and total calcium in cells and introduces a different approach for examining the role of this important element in cell physiology. PMID- 2928309 TI - Altered binding of human histone gene transcription factors during the shutdown of proliferation and onset of differentiation in HL-60 cells. AB - Two sites of protein-DNA interaction have been identified in vivo and in vitro in the proximal promoter regions of an H4 and an H3 human histone gene. In proliferating cells, these genes are transcribed throughout the cell cycle, and both the more distal site I and the proximal site II are occupied by promoter binding factors. In this report we demonstrate that during the shutdown of proliferation and onset of differentiation of the human promyelocytic leukemia cell line HL-60 into cells that exhibit phenotypic properties of monocytes, histone gene expression is down-regulated at the level of transcription. In vivo occupancy of site I by promoter factors persists in the differentiated HL-60 cells, but protein-DNA interactions at site II are selectively lost. Furthermore, in vitro binding activity of the site II promoter factor HiNF-D is lost in differentiated cells, and nuclear extracts from differentiated cells do not support in vitro transcription of these histone genes. Our results suggest that the interaction of HiNF-D with proximal promoter site II sequences plays a primary role in rendering cell growth-regulated histone genes transcribable in proliferating cells. It appears that while cell-cycle control of histone gene expression is mediated by both transcription and mRNA stability, with the shutdown of proliferation and onset mRNA stability, with the shutdown of proliferation and onset of differentiation, histone gene expression is regulated at the transcriptional level. PMID- 2928311 TI - Rat tissues express serum amyloid A protein-related mRNAs. AB - Serum amyloid A (SAA) is a small (12 kDa) acute-phase apoprotein of high density lipoprotein found in mammals. It is also the precursor to amyloid protein A, the main protein constituent of fibrils found in amyloidosis secondary to chronic or recurrent inflammation--e.g., rheumatoid arthritis. However, rats do not develop amyloidosis and SAA is not an apoprotein of rat high density lipoprotein; thus rats appear to be an exception in regard to expression of SAA genes. We report here that rats do have representatives of the SAA gene family and express two distinct SAA mRNAs. Moreover, the pattern of genes expressed among tissues, and their induction by inflammatory agents, is similar to that of related mouse genes. RNA from various tissues of normal and injured rats was examined by RNA blot hybridization with SAA cDNA and complementary RNA probes for the three murine SAA genes. A SAA mRNA of approximately 400 nucleotides related to mouse SAA1 and SAA2 mRNAs reached a high level in liver 24 hr after injection of bacterial lipopolysaccharide. No extra-hepatic tissues were found to express the SAA1/SAA2-related mRNA. Turpentine induced two hepatic SAA1/SAA2-related mRNAs of approximately 400 and approximately 500 nucleotides in length. Liver SAA1/SAA2 related mRNA hybrid selected and translated in a wheat germ protein-synthesizing system, from lipopolysaccharide- and turpentine-injected rats, produced a single protein with an estimated molecular mass of 8 kDa. This rat liver SAA-related mRNA appears to lack a highly conserved coding region for portions of two amphipathic helical domains and the joining sequence. An mRNA related to mouse SAA3 was found expressed at a high level in lung after lipopolysaccharide but not following turpentine injection. This mRNA was also expressed at high levels in ileum and large intestine of control rats and was not found in the liver of control or challenged rats. These observations show that the SAA gene family is present and expressed in rats and that its expression is found under situations similar to those found in mice. This lends support for the importance of the SAA gene family in the response to injury by vertebrates. PMID- 2928312 TI - Loss of competence in amphibian induction can take place in single nondividing cells. AB - The ability of ectodermal tissue to be induced to form mesoderm is lost during gastrula stages in Xenopus embryos. We have examined the extent to which this loss of competence depends on intercellular interactions, cell division, or protein synthesis. We find that ectoderm, when separated from a whole embryo as soon as the early blastula stage, and even when dissociated into its component cells, loses its competence at the normal time. When cell division was arrested by culturing isolated cells in solid medium, the time of competence loss was unaffected. To test whether protein synthesis is required for competence loss, ectoderm was treated with cycloheximide during the normal time that competence is lost; in some cases, this treatment had no effect and in others it prolonged competence, but only slightly. We conclude that the loss of mesodermal competence is a highly autonomous process in ectodermal cells, taking place in the absence of cell communication or cell division. PMID- 2928313 TI - Identification of mutations leading to the Lesch-Nyhan syndrome by automated direct DNA sequencing of in vitro amplified cDNA. AB - The Lesch-Nyhan (LN) syndrome is a severe X chromosome-linked disease that results from a deficiency of the purine salvage enzyme hypoxanthine phosphoribosyltransferase (HPRT). The mutations leading to the disease are heterogeneous and frequently arise as de novo events. We have identified nucleotide alterations in 15 independently arising HPRT-deficiency cases by direct DNA sequencing of in vitro amplified HPRT cDNA. We also demonstrate that the direct DNA sequence analysis can be automated, further simplifying the detection of new mutations at this locus. The mutations include DNA base substitutions, small DNA deletions, a single DNA base insertion, and errors in RNA splicing. The application of these procedures allows DNA diagnosis and carrier identification by the direct detection of the mutant alleles within individual families affected by LN. PMID- 2928314 TI - Ancient DNA: extraction, characterization, molecular cloning, and enzymatic amplification. AB - Several chemical and enzymatic properties were examined in the DNA extracted from dry remains of soft tissues that vary in age from 4 to 13,000 years and represent four species, including two extinct animals (the marsupial wolf and giant ground sloth). The DNA obtained was invariably of a low average molecular size and damaged by oxidative processes, which primarily manifest themselves as modifications of pyrimidines and sugar residues as well as baseless sites and intermolecular cross-links. This renders molecular cloning difficult. However, the polymerase chain reaction can be used to amplify and study short mitochondrial DNA sequences that are of anthropological and evolutionary significance. This opens up the prospect of performing diachronical studies of molecular evolutionary genetics. PMID- 2928315 TI - A general native-state method for determination of proliferation capacity of human normal and tumor tissues in vitro. AB - An important need in cancer research and treatment is a physiological means in vitro by which to assess the proliferation capacity of human tumors and corresponding normal tissue for comparison. We have recently developed a native state, three-dimensional, gel-supported primary culture system that allows every type of human cancer to grow in vitro at more than 90% frequency, with maintenance of tissue architecture, tumor-stromal interaction, and differentiated functions. Here we demonstrate that the native-state culture system allows proliferation indices to be determined for all solid cancer types explanted directly from surgery into long-term culture. Normal tissues also proliferate readily in this system. The degree of resolution of measurement of cell proliferation by histological autoradiography within the cultured tissues is greatly enhanced with the use of epi-illumination polarization microscopy. The histological status of the cultured tissues can be assessed simultaneously with the proliferation status. Carcinomas generally have areas of high epithelial proliferation with quiescent stromal cells. Sarcomas have high proliferation of cells of mesenchymal organ. Normal tissues can also proliferate at high rates. An image analysis system has been developed to automate proliferation determination. The high-resolution physiological means described here to measure the proliferation capacity of tissues will be important in further understanding of the deregulation of cell proliferation in cancer as well as in cancer prognosis and treatment. PMID- 2928316 TI - Promotion of wound repair in old mice by local injection of macrophages. AB - Application of peritoneal macrophages to experimentally induced cutaneous wounds of old mice accelerates healing to levels almost comparable to those of untreated young animals. Slightly greater acceleration is observed when macrophages are obtained from young as opposed to old donors. These findings are consistent with a defect in macrophage function as a cause of impaired wound healing in senescence and suggest a possible therapeutic strategy. PMID- 2928317 TI - Encapsulation of doxorubicin in liver-targeted erythrocytes increases the therapeutic index of the drug in a murine metastatic model. AB - Doxorubicin-loaded, glutaraldehyde-treated murine erythrocytes, once reinjected into circulation, are rapidly taken up by liver and lungs and behave as an organ targeted, slow delivery system for the encapsulated drug. The antitumor activity of encapsulated doxorubicin (former generic name, adriamycin) was compared with that of the free drug in a murine hepatic and pulmonary tumor model. This was obtained by intrasplenic injection of L1210 lymphoma cells followed by splenectomy. Different schedules of treatment of tumor-bearing mice with erythrocyte-encapsulated or free doxorubicin were investigated. The optimal schedule of treatment for free doxorubicin proved to be i.v. bolus administration on the day of splenectomy. Under these conditions, the dose producing 50% inhibition of metastatic growth in the liver, as measured by inhibition of 5 [125I]iodo-2'-deoxyuridine uptake 9 days after tumor induction, was 6.3 mg/kg for free doxorubicin and 0.48 mg/kg for the encapsulated drug. In these conditions pulmonary tumor development was even more efficiently prevented by encapsulated doxorubicin as compared with the free drug. The values of the therapeutic index (TI), defined as the ratio between the maximal tolerated dose (LD10) and the minimal effective dose (ED90, producing 90% inhibition of liver metastatic growth), were 4.2 and 1.8 for encapsulated and free doxorubicin, respectively. PMID- 2928318 TI - Gangliosides potentiate in vivo and in vitro effects of nerve growth factor on central cholinergic neurons. AB - The effects of nerve growth factor beta (beta-NGF) and ganglioside GM1 on forebrain cholinergic neurons were examined in vivo and in vitro. Following unilateral decortication of rats, GM1 (5 mg/kg per day) administered intracerebroventricularly could protect forebrain cholinergic neurons of the nucleus basalis magnocellularis from retrograde degeneration in a manner comparable to beta-NGF. Administered in combination with beta-NGF, GM1 produced a significant increase in choline acetyltransferase activity in the nucleus basalis magnocellularis and remaining cortex ipsilateral to the lesion. Concentrations of GM1 that were ineffective when administered alone in this lesion model, when given with beta-NGF, potentiated beta-NGF effects in both of the above brain areas. In dissociated septal cells in vitro, an increase in choline acetyltransferase activity was noted at beta-NGF concentrations as low as 0.1 pM and reached a plateau at 1 nM. A moderate (up to 35%) stimulation of choline acetyltransferase activity was observed with 10 microM GM1. The application of beta-NGF in combination with 10 microM GM1 or 0.1 microM GM1, a concentration that is ineffective in these cultures, produced a much greater increase in choline acetyltransferase activity than did beta-NGF alone. These observations support the idea that exogenously applied gangliosides can elicit trophic responses in cholinergic neurons of the central nervous system. That GM1 increases and even potentiates beta-NGF effects suggests that some of the trophic actions of this compound may be mediated through endogenous trophic factors. PMID- 2928319 TI - Resistance to axonal degeneration after nerve compression in experimental diabetes. AB - To determine the effect of diabetes on the development of axonal degeneration after acute nerve compression, the mobilized peroneal nerves of rats with streptozotocin-induced diabetes and of control rats were compressed at 150 mmHg (1 mmHg = 133 Pa) for 30 min by using specially devised cuffs. At three intervals after compression--3 days, rats diabetic for 31 wk; 14 days, diabetic for 6 wk; and 24 days, diabetic for 31 wk--groups of nerves were studied to assess numbers and sizes of fibers above, at, and below the cuff and to assess frequency of fiber degeneration in teased fibers from nerve distal to the cuff. Teased fibers with pathologic abnormalities were more frequent in nerves from controls than in nerves from diabetic rats in all three groups but the difference was statistically significant only at 3 and 14 days after compression. The lack of significant difference at 24 days may be explained by higher rates of disappearance of degenerating products and of fiber regeneration at 24 than at 3 and 14 days. This study provides evidence that in addition to delaying the reported functional deficit of vibratory detection threshold and conduction block during nerve compression, diabetes also may partially prevent axonal injury. Low nerve myo-inositol concentration did not predispose diabetic nerve to acute compression injury. If these results also apply to human diabetes and if repeated acute compression is involved in the genesis of fiber degeneration in entrapment, then a higher frequency of entrapment neuropathy among diabetics might be due to mechanisms other than increased susceptibility of fibers to acute compression- e.g., possibly to greater constriction of nerve due to pathologic alterations of the carpal ligament. PMID- 2928320 TI - Specific estrogen-induced cell proliferation of cultured Syrian hamster renal proximal tubular cells in serum-free chemically defined media. AB - It has long been recognized that the renal proximal tubular epithelium of the hamster is a bona fide estrogen target tissue. The effect of estrogens on the growth of proximal tubule cell explants and dissociated single cells derived from these explant outgrowths has been studied in culture. Renal tubular cells were grown on a PF-HR-9 basement membrane under serum-free chemically defined culture conditions. The cells of tissue explant outgrowths exhibited ultrastructural features typical of proximal tubules including junctional complexes, numerous mitochondria, peroxisomes, and microvilli. At 7-14 days in culture, cell number was enhanced 3-fold in the presence of either 17 beta-estradiol or diethylstilbestrol. Maximal proliferative response was observed at hormone concentrations of 0.6-1 nM. A similar 3-fold increase in cell number was also seen at 1 nM 17 beta-estradiol in subcultured dissociated single tubular cells derived from hamster renal tubular explant outgrowths at 21 days in culture. Neither progesterone, 5 alpha-dihydrotestosterone, nor the inactive diethylstilbestrol metabolite beta-dienestrol elicited this mitogenic effect. Concomitant exposure of tamoxifen at 3-fold molar excess in culture completely abolished the increase in cell number seen with 17 beta-estradiol. Tubular cells obtained from hamster medulla did not exhibit this proliferative response when exposed similarly to 17 beta-estradiol or diethylstilbestrol. The proliferative effect of estrogens on proximal tubular cell growth appears to be species specific since 17 beta-estradiol did not alter the growth of either rat or guinea pig proximal tubules in culture. In addition, at 7-10 days in culture in the presence of 17 beta-estradiol, [3H]thymidine labeling of hamster tubular cells was enhanced 3-fold. A similar increase in mitoses was also observed in cultures containing these potent estrogens during the same time interval of estrogen exposure. These results clearly indicate that estrogens can directly induce primary epithelial cell proliferation at physiologic concentrations and provide strong additional evidence for an important hormonal role in the neoplastic transformation of the hamster kidney. PMID- 2928321 TI - Identification and sequence analysis of a second form of prolactin receptor by molecular cloning of complementary DNA from rabbit mammary gland. AB - Two lambda gt11 clones containing fragments of cDNA encoding the prolactin receptor from rabbit mammary gland were isolated using a rat liver prolactin receptor cDNA probe. An 1848-base-pair open reading frame encodes a mature prolactin-binding protein of 592 amino acids that contains three domains: (i) the extracellular, amino-terminal, prolactin-binding region of 210 residues; (ii) the transmembrane region of 24 residues; and (iii) the intracellular, carboxyl terminal domain of 358 residues. This latter domain is much longer than the cytoplasmic domain (57 residues) previously described for the rat liver prolactin receptor. In addition, the sequence identity of this form of prolactin receptor with the growth hormone receptor is extended in the cytoplasmic domain. PMID- 2928322 TI - High levels of double-stranded transferred DNA (T-DNA) processing from an intact nopaline Ti plasmid. AB - To obtain bacterial-mediated oncogenic transformation of plants, the transferred DNA (T-DNA) of the tumor-inducing (Ti) plasmid of Agrobacterium tumefaciens is transferred to its plant host cells during infection. The initial phases of transformation involve the processing of the T-DNA in the bacterial cell after induction of the vir genes located on the Ti plasmid. The kinetics and conditions of this processing were examined and upon induction with acetosyringone up to 40% of the left and right borders of the T-DNA were cleaved. This cleavage was dependent upon virA, virG, and VirD and was rec-independent. Processed T-DNA was observed within 30 min after induction and was delayed by an increased concentration of phosphate in the induction medium. When DNA was isolated in the absence of protease treatment, the DNA fragment corresponding to the left side of the cut at both the left and right border region exhibited gel retardation, suggesting one or more "pilot" proteins may be involved in T-DNA transfer. Although the relative abundance of a processed product does not necessarily imply relative importance, the preponderance of double-stranded cleavage products suggests that double-stranded T-DNA should be considered as a possible intermediate in T-DNA transfer. PMID- 2928323 TI - Identifying determinants of folding and activity for a protein of unknown structure. AB - We have generated an extensive genetic map of functionally allowed and/or structurally allowed amino acid substitutions in Arc repressor, a DNA binding protein of unknown structure. Analysis of the allowed substitution patterns identifies residues that are likely to be involved in protein function and identifies side chains that play important structural roles, including residues likely to form the hydrophobic core. The identities of approximately one-third of the residues in Arc repressor are functionally important, about one-half are structurally important, and the remainder are unimportant for either structure or function. The patterns of obligatory hydrophobic positions permit strong predictions of secondary structure. PMID- 2928324 TI - Crystal structure of core streptavidin determined from multiwavelength anomalous diffraction of synchrotron radiation. AB - A three-dimensional crystal structure of the biotin-binding core of streptavidin has been determined at 3.1-A resolution. The structure was analyzed from diffraction data measured at three wavelengths from a single crystal of the selenobiotinyl complex with streptavidin. Streptavidin is a tetramer with subunits arrayed in D2 symmetry. Each protomer is an 8-stranded beta-barrel with simple up-down topology. Biotin molecules are bound at one end of each barrel. This study demonstrates the effectiveness of multiwavelength anomalous diffraction (MAD) procedures for macromolecular crystallography and provides a basis for detailed study of biotin-avidin interactions. PMID- 2928325 TI - Proline isomerism leads to multiple folded conformations of calbindin D9k: direct evidence from two-dimensional 1H NMR spectroscopy. AB - A complete analysis of calbindin D9k by two-dimensional 1H nuclear magnetic resonance spectroscopy has established the existence of two conformations for the folded protein in solution. Well-resolved major and minor resonances in a ratio of 3:1 are observed throughout the 1H NMR spectrum. Two-dimensional exchange experiments show that the major and minor species are related by an equilibrium process. Analysis of short proton-proton distances along the peptide backbone, identified by two-dimensional nuclear Overhauser effect spectroscopy, provides unambiguous evidence that the two forms of the folded protein differ only in the isomerization state of the peptide bond between Gly-42 and Pro-43. Cis-trans isomerism of Pro-43 is thereby directly identified as the cause of multiple conformations for the folded protein in solution. In addition, when Pro-43 is mutated to a glycine residue there is no indication of multiple conformations. These results provide evidence for the possibility of conformational heterogeneity in the native state of globular proteins. PMID- 2928326 TI - On the origin and transmission of force in actomyosin subfragment 1. AB - A proximity map showing the three-dimensional arrangement of 12 chemically defined points in actomyosin subfragment 1 is developed and roughly correlated with published electron microscope reconstruction of others. Several additional points and topological relationships in the primary polypeptide chain folding are assimilated into this model. Certain crosslinkings and distance change observations are interpreted as indicators of transmission of force/displacement between the nucleotide-binding and an actin-binding site--i.e., as indications of how energy is transduced in this system. PMID- 2928327 TI - Transforming growth factor beta reverses the glucocorticoid-induced wound-healing deficit in rats: possible regulation in macrophages by platelet-derived growth factor. AB - Transforming growth factor beta (TGF-beta) and the platelet-derived growth factor (PDGF) are potent mitogenic polypeptides which enhance rates of wound healing in experimental animals; in contrast, glucocorticoids inhibit wound repair. The potential of TGF-beta and PDGF to reverse this inhibition in healing was tested in methylprednisolone-treated rats with deficits in skin wound strength of 50%. Single applications of TGF-beta (10-40 pmol per wound, 0.25-1 micrograms) applied locally at the time of wounding fully reversed this deficit in a concentration dependent and highly reproducible manner. Wounds in glucocorticoid-treated animals were characterized by a near total absence of neutrophils and macrophages and by a delayed influx and reduced density of fibroblasts; however, such wounds treated with TGF-beta showed significant increases in wound fibroblasts and in intracellular procollagen type I. PDGF did not reverse the deficit in wound breaking strength in glucocorticoid-treated rats; there were more fibroblasts in the PDGF-treated wounds, but these fibroblasts lacked the enhanced expression of procollagen type I found in TGF-beta-treated wounds. The wound macrophages, required for normal tissue repair, remained absent from both PDGF- and TGF-beta treated wounds in glucocorticoid-treated animals. This result suggested that macrophages might normally act as an intermediate in the induction of procollagen synthesis in fibroblasts of PDGF-treated wounds and that TGF-beta might bypass the macrophage through its capacity to stimulate directly new synthesis of procollagen type I in fibroblasts. Whereas PDGF does not stimulate procollagen synthesis, in a rodent macrophage cell line, PDGF induced a highly significant, time-dependent enhancement of expression of TGF-beta. PMID- 2928328 TI - Tyrosine-specific protein phosphorylation is regulated by glycoprotein IIb-IIIa in platelets. AB - We have previously shown that a number of platelet proteins become phosphorylated at tyrosine residues in response to platelet-activating agents. Here we present two lines of evidence implicating a platelet integrin, glycoprotein IIb-IIIa, in the regulation of a specific subset of these tyrosine phosphorylations. (i) Two peptides that inhibit the binding of fibrinogen and other ligands to gpIIb-IIIa, Arg-Gly-Asp-Ser and His-His-Leu-Gly-Gly-Ala-Lys-Gln-Ala-Gly-Asp-Val, also inhibited the thrombin-induced tyrosine phosphorylation of this subset of proteins. The tetrapeptide Arg-Gly-Glu-Ser, which does not inhibit fibrinogen binding, did not inhibit thrombin-stimulated tyrosine phosphorylation. (ii) Platelets lacking gpIIb-IIIa (from a subject with Glanzmann thrombasthenia) did not undergo this subset of tyrosine phosphorylation in response to thrombin, although other serine, threonine, and tyrosine phosphorylations proceeded normally. These findings suggest a role for tyrosine-specific protein phosphorylation in integrin-mediated cell-matrix recognition. PMID- 2928329 TI - 31P nuclear magnetic resonance study of the metabolic pools of adenosine triphosphate in cultured bovine adrenal medullary chromaffin cells. AB - 31P NMR was used to resolve and determine the relative quantity and mobility of ATP in the cytosolic and vesicular compartments of isolated adrenomedullary chromaffin cells. The cells were cultured on microcarrier beads and superfused with an oxygenated medium--thereby permitting dense suspensions of viable cells to be maintained in the NMR probe for extended time periods. Under these conditions, distinct 31P signals could be seen for ATP within the vesicular and the cytosolic pools. Comparison of the integrated areas of the beta-phosphate resonances from the two ATP pools indicated 77% of the endogenous ATP was in the vesicular pool. From this observation and the assumption that the concentration of ATP in the vesicle is 87.5 mM, the concentration of ATP calculated to be in the cytoplasmic pool was approximately 4 mM. The pH in the vesicle determined from the chemical shift of the gamma-phosphate resonance of vesicular ATP was 5.84 +/- 0.17 (n = 6), slightly higher than the intragranular pH measured in hypoxic cells (5.57 +/- 0.15, n = 8). Spin-lattice relaxation times of ATP 31P resonances in the vesicular pool were from 12 to 14 times shorter than the ATP resonances in the cytosol, corresponding to a decrease in molecular mobility due to incorporation of ATP within a catecholamine-storage complex. PMID- 2928330 TI - Phosphorylation and associated translocation of the 87-kDa protein, a major protein kinase C substrate, in isolated nerve terminals. AB - A protein of 87 kilodaltons (87 kDa) was previously identified as a major specific substrate for protein kinase C in neuronal and other tissues. We have now studied the effect of protein kinase C-catalyzed phosphorylation of this protein on its association with membranes in isolated nerve terminals (synaptosomes) from rat cerebral cortex. Incubation of synaptosomal membranes under conditions associated with activation of protein kinase C led to the release of the phosphorylated 87-kDa protein into the incubation medium. In intact synaptosomes, activation of protein kinase C by phorbol esters or by depolarization-induced Ca2+ influx caused an increased phosphorylation of the 87 kDa protein and its translocation from membrane to cytosol. This translocation showed time courses, calcium dependency, and reversibility similar to those observed for the protein kinase C-induced phosphorylation of the protein. These results suggest that protein kinase C-catalyzed phosphorylation of the 87-kDa protein is responsible for its subcellular translocation into the cytosol of nerve terminals. PMID- 2928331 TI - Neonatal induction of a nuclear protein that binds to the c-fos enhancer. AB - The expression of the c-fos gene is transiently induced at birth in most organs in the mouse. To study the basis of this induction we searched for a nuclear factor that binds to the 5' regulatory region of the c-fos gene. Gel mobility shift assays with tissue extracts revealed fast (band I) and slow (band III) migrating bands, which represent factor binding to the c-fos enhancer, termed the serum response element (SRE). Neonatal extracts preferentially elicited band I, with low or undetectable levels of band III, whereas fetal and adult extracts generated predominantly band III, with reduced levels of band I. These results indicate that the SRE-binding activity changes during perinatal development and that the appearance of band I, which coincides with diminution of band III, correlates with neonatal c-fos induction. Methylation interference and competition analyses showed that the neonatal factor (band I) binds to the SRE at a site different from the adult factor (band III). DNA-binding activity of the adult factor, but not the neonatal factor, was sensitive to phosphatase treatment. Furthermore, the adult factor, but not the neonatal factor, shared antigenic specificity with the human serum response factor (SRF) that is expressed in cultured cells irrespective of c-fos gene induction. We conclude that band I in neonates represents a SRE-binding factor that is distinct from the SRF, which may be responsible for the neonatal induction of the c-fos gene. The band III factor was indistinguishable from the SRF in all criteria tested. PMID- 2928332 TI - Lack of DNA homology in a pair of divergent chromosomes greatly sensitizes them to loss by DNA damage. AB - Chromosomal DNA is considered a priori to be a target for the induction of numerical (whole chromosome) aneuploidy in mitotic cells. If true, DNA repair would be expected to contribute to genome stability. One type of repair that appears to play an important role in the response of many organisms to DNA damaging agents involves recombination. Using the yeast Saccharomyces cerevisiae containing a pair of DNA divergent (homoeologous) chromosomes, we have been able to determine the importance of recombinational repair of DNA damage in the maintenance of chromosome number. Specifically, the induction of aneuploidy by ionizing radiation has been examined in diploids that had one chromosome III replaced by a divergent chromosome from Saccharomyces carlsbergensis. The chromosomes are functionally equivalent but lack precise DNA homology over one half their length. The absence of homology, and thus the opportunity for recombinational repair (presumably of DNA double-strand breaks) in the divergent chromosomes, results in high levels (5-10%) of aneuploidy for chromosome III at doses of radiation resulting in almost no killing. For homologous chromosomes, the frequency of loss is 20-50 times lower. PMID- 2928333 TI - Exchange of terminal portions of X- and Y-chromosomal short arms in human XY females. AB - Human Y(+) XX maleness has been shown to result from an abnormal terminal Xp-Yp interchange that can occur during paternal meiosis. To test whether human XY females are produced by the same mechanism, we followed the inheritance of paternal pseudoautosomal loci and Xp22.3-specific loci in two XY female patients. Y-specific sequences and the whole pseudoautosomal region of the Y chromosome of their fathers were absent in these patients. However, the entire pseudoautosomal region and the X-specific part of Xp22.3 distal to the STS locus had been inherited from the X chromosome of the respective father. This Xp transfer to Yp was established by in situ hybridization experiments showing an Xp22.3-specific locus on Yp in both cases. Such results demonstrate that an abnormal and terminal X-Y interchange generated the rearranged Y chromosome of these two XY females; they appear to be the true countertype of Y(+) XX males. In these patients, who also display some Turner stigmata, the Y gene(s) involved in this phenotype is (are) localized to interval 1 or 2. If the loss of such gene(s) affects fetal viability, their proximity to TDF would account for the underrepresentation of interchange 46,XY females compared with Y(+) XX males. PMID- 2928334 TI - Polycythemia in transgenic mice expressing the human erythropoietin gene. AB - Erythropoietin is a glycoprotein hormone that regulates mammalian erythropoiesis. To study the expression of the human erythropoietin gene, EPO, 4 kilobases of DNA encompassing the gene with 0.4 kilobase of 5' flanking sequence and 0.7 kilobase of 3' flanking sequence was microinjected into fertilized mouse eggs. Transgenic mice were generated that are polycythemic, with increased erythrocytic indices in peripheral blood, increased numbers of erythroid precursors in hematopoietic tissue, and increased serum erythropoietin levels. Transgenic homozygotes show a greater degree of polycythemia than do heterozygotes as well as striking extramedullary erythropoiesis. Human erythropoietin RNA was found not only in fetal liver, adult liver, and kidney but also in all other transgenic tissues analyzed. Anemia induced increased human erythropoietin RNA levels in liver but not kidney. These transgenic mice represent a unique model of polycythemia due to increased erythropoietin levels. PMID- 2928335 TI - High frequency of large spontaneous deletions of DNA in tumor-derived CHEF cells. AB - Spontaneous mutations arising at the HPRT locus were examined in 126 mutants recovered from a series of six CHEF-derived cell lines. Altered restriction fragment patterns were characterized by Southern blot hybridization, and gene expression by RNA blot hybridization. Point mutants and gene-expression mutants predominated in the control (nontumorigenic) 18-1D-3 cell line and in two tumor derived lines, one of which (16-2 Tuk 4) displayed a mutator phenotype. In the other three lines, the majority of mutants had large partial or whole gene deletions. These results suggest that mutant enzymes in DNA replication or repair play an important role in neoplastic progression by causing extensive deletions in DNA, including excision of genes that encode tumor-suppressor functions, and deletion of regulatory sequences in protooncogenes. PMID- 2928337 TI - Muscle coenzyme Q deficiency in familial mitochondrial encephalomyopathy. AB - The electron transport system of muscle mitochondria was examined in a familial syndrome of lactacidemia, mitochondrial myopathy, and encephalopathy. The propositus, a 14-year-old female, and her 12-year-old sister had suffered from progressive muscle weakness, abnormal fatigability, and central nervous system dysfunction since early childhood. In the propositus, the state 3 respiratory rate of muscle mitochondria with NADH-linked substrates and with succinate was markedly reduced. The levels of cytochromes a + a3, b, and c + c1 were normal. The activities of complexes I, II, III, and IV of the electron transport chain were normal or increased. By contrast, the activities of complex I-III and of complex II-III, both of which need coenzyme Q10 (CoQ10), were abnormally low. On direct measurement, the mitochondrial CoQ10 content was 3.7% of the mean value observed in 10 controls. Serum and cultured fibroblasts of the propositus had normal CoQ10 contents. In the younger sister, the respiratory activities and CoQ10 level of muscle mitochondria were similar to those observed in the propositus. The findings establish CoQ10 deficiency as a cause of a familial mitochondrial cytopathy and suggest that the disease results from a tissue specific defect of CoQ10 biosynthesis. PMID- 2928336 TI - Comparison of the secondary structures of human class I and class II major histocompatibility complex antigens by Fourier transform infrared and circular dichroism spectroscopy. AB - We have examined the secondary structures of human class I and class II histocompatibility antigens in solution by Fourier transform infrared spectroscopy and circular dichroism in order to compare the relative amounts of alpha-helix, beta-sheet, and other structures, which are crucial elements in the comparison of the protein structures. Quantitation of infrared spectra of papain solubilized HLA-A2, HLA-B7, and DR1 in phosphate buffer gave alpha-helix contents of 17%, 8%, and 10% and beta-sheet contents of 41%, 48%, and 53%, respectively. By circular dichroism, papain-solubilized HLA-A2, HLA-B7, and DR1 were also found to have comparable alpha-helix contents (e.g., 8%, 20%, and 17%, respectively). Circular dichroism analysis for beta-sheet gave 29% for papain-solubilized HLA-B7 and 42% for papain-solubilized DR1. The value for papain-solubilized HLA-A2 (74%) was anomalous. It is proposed that Trp-107 of HLA-A2, missing in both HLA-B7 and DR1, may be responsible for much of the anomaly. Due to the uncertainties inherent in quantitation of the amounts of secondary structures by both spectral methods, the differences in the contents of alpha-helix and beta-sheet in the three proteins are not considered significant. However, differences in the nature of the beta-sheet structures are suggested by infrared spectroscopy. These results provide physical evidence for an overall structure of class II antigens modeled on that of class I antigens. PMID- 2928338 TI - Ca2+-channel blockers inhibit the action of recombinant platelet-derived growth factor in vascular smooth muscle cells. AB - Human platelet-derived growth factor (PDGF) is mainly composed of two polypeptide chains (PDGF-AB). All three possible dimeric forms of PDGF--i.e., PDGF-AA, PDGF BB and PDGF-AB--exist in nature. We have used two recombinant PDGF homodimers to determine the roles of each isoform in the activation of phosphatidylinositol turnover in vascular smooth muscle cells (VSMC) isolated from rat thoracic aorta, their mitogenic effect on VSMC, and their vasoconstrictor effect on intact strips of aortic vascular tissue. Three Ca2+-channel blockers, nifedipine, verapamil, and diltiazem, were used as antagonists for investigating the PDGF-dependent changes mediated by the homodimers. PDGF-BB had a greater efficacy than PDGF-AA on inositol 1,4,5-trisphosphate release, on the formation of diacylglycerol, and on Ca2+ mobilization, which was also associated with vasoconstrictor activity and effective mitogenicity. PDGF-AA, on the other hand, was more potent than PDGF-BB in stimulating protein kinase C. In all instances, the activation of the phosphatidylinositol turnover by the two homodimers was inhibited by the Ca2+ channel blockers. PMID- 2928339 TI - Lipoproteins alter the catalytic behavior of the platelet-activating factor acetylhydrolase in human plasma. AB - Platelet-activating factor (PAF) has been implicated as a mediator of inflammation, allergy, shock, and thrombosis. A specific degradative enzyme, PAF acetylhydrolase (EC 3.1.1.47), is found in plasma and could regulate the concentration of PAF in blood. In plasma, 70% of the PAF acetylhydrolase is found with low density lipoprotein (LDL), and the remainder is in high density lipoprotein (HDL). In previous studies we found that with subsaturating concentrations of PAF the activity in LDL seemed to be the relevant one; e.g., depletion of LDL slowed degradation of PAF, while removal of HDL accelerated the degradation slightly. We have pursued this observation by using plasma from humans with lipoprotein mutations. In abetalipoproteinemia, all of the PAF acetylhydrolase activity was in HDL, whereas in Tangier disease all of the activity was in LDL. In both conditions the total activity measured in an optimized assay was normal or increased. However, when we measured the t1/2 of PAF in plasma, we found that it was prolonged in subjects with abetalipoproteinemia compared to normal controls. Conversely, the t1/2 in Tangier plasma was shortened. We next demonstrated that the PAF acetylhydrolase in HDL was recognized by an antibody to the enzyme purified from LDL, establishing that the enzyme in the two particles is the same protein. Finally, we inactivated the PAF acetylhydrolase in isolated lipoprotein particles and then reconstituted them with enzyme from the opposite particle. The reconstituted particles were used to measure the t1/2 of PAF, and we again found that the LDL particle was more efficient. We conclude that the lipoprotein environment of the PAF acetylhydrolase markedly influences its catalytic behavior. This may be important in pathophysiology and will complicate attempts to assess the role of this enzyme in such circumstances. PMID- 2928340 TI - Isolation and characterization of the human parathyroid hormone-like peptide gene. AB - A parathyroid hormone-like peptide (PTH-LP) has recently been identified in human tumors associated with the syndrome of humoral hypercalcemia of malignancy. The peptide appears to be encoded by a single-copy gene that gives rise to multiple mRNAs that are heterogeneous at both their 5' and their 3' ends. Alternative RNA splicing is responsible for the 3' heterogeneity and results in mRNAs encoding three different peptides, each with a unique C terminus. We have isolated and characterized the human PTHLP gene. The gene is a complex transcriptional unit spanning more than 12 kilobases of DNA and containing six exons. Two 5' exons encode distinct 5' untranslated regions and are separated by a putative promoter element, indicating that the gene either has two promoter or is alternatively spliced from a single promoter upstream of the first exon. The middle portion of the PTHLP gene, comprising exons 2-4, has an organizational pattern of introns and exons identical to that of the parathyroid hormone gene, consistent with a common ancestral origin of these two genes. Exon 4 of the PTHLP gene encodes the region common to all three peptides and the C terminus of the shortest peptide, and exons 5 and 6 encode the unique C termini of the other two peptides. Northern analysis of mRNAs from four human tumors of different histological types reveals the preferential use of 3' splicing patterns by individual tumors. PMID- 2928341 TI - Molecular cloning of feline immunodeficiency virus. AB - Feline immunodeficiency virus (FIV) is a T-lymphotropic retrovirus associated with immunodeficiency and opportunistic infections in cats. The discovery of FIV provides an opportunity for the development of a small animal model for AIDS. To initiate the molecular and biological characterization of FIV, cDNA clones were synthesized and used to isolate a proviral clone of FIV. Molecular cross hybridization analysis of FIV with five lentiviruses revealed that nucleotide sequence similarities exist between FIV and these lentiviruses in the gag-pol genes. However, nucleotide-sequence similarities were not seen upon comparison of the FIV long terminal repeat sequence with known viral sequences. Common antigenic determinants appeared to be shared by FIV, caprine arthritis encephalitis virus, and visna virus as shown by serological cross-reactivity of rabbit antibodies to caprine arthritis encephalitis virus and visna virus with the putative FIV core protein p28. These studies demonstrated that FIV is a member of the lentivirus subfamily and is distantly related to the AIDS lentiviruses of primates. Importantly, progeny virions of our molecular clone were infectious for experimentally inoculated cats. The availability of an infectious molecular clone will make possible a detailed dissection of the molecular pathogenesis of FIV, which may facilitate the development of vaccine and therapeutic strategies for AIDS. PMID- 2928343 TI - Regulation of neuronal oxytocin mRNA by ovarian steroids in the mature and developing hypothalamus. AB - We have examined the changes in neuronal expression of oxytocin mRNA in the perinatal and mature female rat as a function of endogenous gonadal steroids. Northern blot analysis demonstrated a significant developmental increase in the abundance of oxytocin mRNA in the female brain concomitant with puberty. Ovariectomy of adult females decreased total brain oxytocin mRNA to significantly lower levels. In contrast, lactating mothers had increased levels of neuronal oxytocin mRNA. In situ hybridization analysis of neuronal oxytocin mRNA in adolescent, mature virgin, and ovariectomized virgin female brains demonstrated that the location and number of neurons expressing oxytocin mRNA was unchanged and that total brain oxytocin mRNA differences were attributable to amounts expressed per neuron. Differences in mRNA abundance were noted in oxytocin neurons throughout the hypothalamus, including those known to project as magnocellular neurons to the neurohypophysis and those of parvocellular origin thought to make wholly intracerebral connections. This developmental and dynamic regulation of oxytocin mRNA levels during gonadal maturation may coordinate the peripheral and central effects of this peptide on the reproductive biology of the female rat. PMID- 2928342 TI - Cloning of a cDNA encoding the rat high molecular weight neurofilament peptide (NF-H): developmental and tissue expression in the rat, and mapping of its human homologue to chromosomes 1 and 22. AB - Neurofilaments (NFs) are the intermediate filaments specific to nervous tissue. They are probably essential to the tensile strength of the neuron, as well as to transport of molecules and organelles within the axon. Three peptides with apparent molecular masses of approximately 68 (NF-L), 145 (NF-M), and 200 (NF-H) kDa appear to be the major components of NF. The expression of these peptides is specific to nervous tissue and is developmentally regulated. Recently, complete cDNAs encoding NF-L and NF-M, and partial cDNAs encoding NF-H, have been described. To better understand the normal and pathophysiology of NFs we chose to clone the cDNA encoding the rat NF-H peptide. Using monoclonal antibodies that recognized NF-H, we screened a rat brain lambda gt11 library and identified a clone that contained a 2100-nucleotide cDNA insert representing the carboxyl terminal portion of the NF-H protein. Anti-fusion protein antibodies recognized the NF-H peptide on immunoblots and stained fibrillar structures only in neurons. The cDNA recognized a 4500-nucleotide polyadenylated mRNA that was present only in nervous tissue and a 3500-nucleotide mRNA in adrenal. Brain NF-H mRNA levels were tightly developmentally regulated and paralleled the levels of NF-H peptide on immunoblots. Nuclear runoff studies showed that the 20-fold developmental increase in the NF-H message was due only in part to a 4-fold increase in its transcription rate. Levels of NF-H mRNA varied 20-fold among brain regions, with highest levels in pons/medulla, spinal cord, and cerebellum, and lowest levels in olfactory bulb and hypothalamus. Transcription studies revealed only a 2-fold difference in the transcription rates among these brain regions. Based on these results, we infer that half of the developmental increase and most of the interregional variation in the levels of the NF-H mRNA are mediated through message stabilization. Sequence information revealed that the carboxyl-terminal region of the NF-H peptide contained a unique serine-, proline-, alanine-, glutamic acid-, and lysine-rich repeat. The serine residues are likely sites of phosphorylation in the mature peptide. Genomic blots revealed a single copy of the gene in the rat genome and two copies in the human genome. In situ hybridizations performed on human chromosomes mapped the NF-H gene to chromosomes 1 and 22. Whether one copy is a pseudogene remains to be determined. PMID- 2928344 TI - Prostaglandin E2 and its methyl ester reduce cataplexy in canine narcolepsy. AB - The effects of intravenous administration of prostaglandins (PGs) were investigated in genetically narcoleptic Doberman pinschers. The treatment of narcoleptic dogs with PGE2 and PGE2 methyl ester, but not PGD2 and PGD2 methyl ester, induced a dose-dependent reduction of canine cataplexy, a dissociated manifestation of rapid-eye-movement sleep. The effect was specific and not associated with any change in other behavior. Furthermore, the effect was long lasting (up to 2 hr) and could not be explained by the acute cardiovascular changes seen after intravenous PG administration. PGE2 methyl ester, a lipophilic derivative of PGE2 with more central penetration than PGE2, was 4 times more potent than PGE2. These results indicate that PGE2 modifies cataplexy through a central effect and suggest that this prostaglandin may play a role in rapid-eye movement sleep regulation. PMID- 2928345 TI - Striatal phosphoproteins in Parkinson disease and progressive supranuclear palsy. AB - This study was undertaken to evaluate the levels of cAMP-regulated phosphoproteins in the striatum of patients with neurodegenerative diseases of the dopaminergic system. Postmortem samples of caudate nucleus and putamen from 24 control subjects, 23 patients with Parkinson disease, and 13 patients with progressive supranuclear palsy were studied with immunoblotting techniques. The levels of tyrosine hydroxylase were reduced in patients with Parkinson disease (levels were 24% and 10% of controls in caudate nucleus and putamen, respectively) and with progressive supranuclear palsy (levels were 11% and 6% of controls in caudate nucleus and putamen, respectively). Five phosphoproteins, which are present in striatal neurons and are likely to play a role in the postsynaptic actions of dopamine, were measured. These included ARPP-16, ARPP-19, ARPP-21 (cAMP-regulated phosphoproteins of Mr 16,000, 19,000, and 21,000, respectively), DARPP-32 (dopamine- and cAMP-regulated phosphoprotein of Mr 32,000), and phosphatase inhibitor I. The levels of these phosphoproteins were inversely correlated with postmortem delay. In brains of patients with Parkinson disease or progressive supranuclear palsy with postmortem delays comparable to those of controls, the levels of these proteins as well as those of synaptic (synapsin I and synaptophysin) and glial (glial fibrillary acidic protein and myelin basic protein) markers were not significantly modified. We conclude that the levels of several phosphoproteins involved in signal transduction in striatal neurons are not altered in Parkinson disease and progressive supranuclear palsy. This observation supports the view that the striatal output neurons are intact in both diseases. PMID- 2928347 TI - Steroid hormones: modulators of Na+ absorption and Cl- secretion in cultured tracheal epithelia. AB - Cultures of tracheal epithelial cells from adult nonpregnant female rabbits maintained a different balance of Na+ absorption and Cl- secretion from cells of pregnant animals and fetal cultures. Cells of nonpregnant rabbits had a large Na+ absorptive current (11 microA/cm2 or 53% of baseline short circuit current) and a small Cl- secretory current (2.4 microA/cm2 or 11%). In contrast, fetal cells had greater Cl- secretion (15.1 microA/cm2 or 61%) and much less Na+ absorption (1.6 microA/cm2 or less than 10%). Cells of pregnant animals had amounts of Cl- secretion (11.4 microA/cm2 or 41%) and Na+ absorption (6.7 microA/cm2 or 22%) that were in between that of fetal and adult nonpregnant animals. In addition to these striking differences in baseline ion transport among the three groups, epinephrine was found to stimulate Cl- secretion in cells from pregnant rabbits, both Na+ absorption and Cl- secretion in cells from nonpregnant animals, and neither in fetal cells. Steroid hormones of pregnancy, progesterone and estradiol, when added to cells cultured from nonpregnant rabbits, altered the magnitudes of the individual transport pathways to mimic cells cultured from pregnant animals. In addition to changing baseline transport, these steroids modified the epinephrine-stimulated currents to resemble those in the fetus and in pregnancy. We conclude that steroid hormones regulate the balance of Na+ absorption and Cl- secretion in tracheal epithelia in utero and in adulthood. PMID- 2928348 TI - The envelope proteins from purified respiratory syncytial virus protect mice from intranasal virus challenge. AB - A lyophilized subunit vaccine prepared from purified respiratory syncytial virus, which contained the envelope glycoproteins F and G and the nonglycosylated matrix protein VPM, was tested in SJL mice for its ability to protect the lungs of mice from intranasal viral challenge. Initially, the mice were injected subcutaneously with one, two, or three doses of 5 or 25 micrograms of vaccine in 50% complete Freund's adjuvant or with complete Freund's adjuvant or phosphate-buffered saline only. Although none of the mice produced neutralizing serum antibody, three doses of 25 micrograms elicited antibodies to F, G, and VPM. Despite the absence of detectable neutralizing antibodies, the lungs of 93% of the vaccinated mice were protected from intranasal viral challenge. Because the initial protocol did not elicit neutralizing antibodies and a few single-dose animals were not protected, a second vaccine trial was carried out. For these studies the priming dose was increased to 50 micrograms, which was followed, in half the vaccine recipients, by a second dose of 25 micrograms. Mice given the priming dose of vaccine produced antibody to G and showed no neutralizing activity, whereas the mice given two doses of vaccine produced antibodies to G, F, and VPM and also displayed neutralizing activity for respiratory syncytial virus. The lungs of 100% of the vaccine recipients in this trial were protected from intranasal challenge. Although the vaccine elicited antibody to VPM, this response did not correlate with protection. In addition, examination of the sera from unimmunized mice recovering from respiratory syncytial virus infection revealed a serum antibody profile similar to that noted for humans, lacking antibody to VPM. Thus, the data show that a combined glycoprotein subunit vaccine affords complete protection to viral challenge and offers an approach to develop a multivalent subunit vaccine. PMID- 2928346 TI - Muscarinic agonists and phorbol esters increase tyrosine phosphorylation of a 40 kilodalton protein in hippocampal slices. AB - We have used the hippocampal slice preparation to investigate the regulation of protein tyrosine phosphorylation in brain. After pharmacological treatment of intact slices, proteins were separated by electrophoresis, and levels of protein tyrosine phosphorylation were assessed by immunoblotting with specific anti phosphotyrosine antibodies. Phorbol esters, activators of the serine- and threonine-phosphorylating enzyme protein kinase C, selectively increase tyrosine phosphorylation of a soluble protein with an apparent molecular mass of approximately 40 kilodaltons. Muscarinic agonists such as carbachol and oxotremorine M that strongly activate the inositol phospholipid system also increase tyrosine phosphorylation of this protein. Neurotransmitter activation of the inositol phospholipid system and protein kinase C appears to trigger a cascade leading to increased tyrosine phosphorylation. PMID- 2928349 TI - Oxidative stress leads to inhibition of calcium transport by sarcoplasmic reticulum in skeletal muscle. AB - Iron administration results in the development of oxidative stress in skeletal muscles, as evidenced by increases in amounts of lipid oxidation fluorescent end products, decreases in vitamin E concentration, and inhibition of calcium transport by sarcoplasmic reticulum. Exhaustive physical loading or hyperoxia, or their combination, does not lead to apparent modification in calcium transport by sarcoplasmic reticulum in skeletal muscle homogenates. However, physical loading or hyperoxia does in fact induce oxidative stress since they magnify the effect of iron loading on the inhibition of calcium transport. PMID- 2928350 TI - Regeneration of ascorbic acid by rat colon. AB - Plants and animals alike use ascorbic acid in a variety of reactions that result in net generation of dehydro-L-ascorbic acid. The ability to reduce dehydro-L ascorbic acid back to ascorbic acid would conserve "total ascorbate" and would help to maintain the toxic oxidized form of the molecule at a low level. This study evaluated the rate of dehydro-L-ascorbic acid reduction either by following the rate of NADPH consumption or by analysis of the amount of 14C-labeled dehydro L-ascorbic acid converted to ascorbic acid. A large percentage of the NADPH consumed by a semipurified preparation of rat colonic mucosa in vitro was dependent on the presence of dehydro-L-ascorbic acid. The tissue factor active in regenerating ascorbic acid is intermediate in size between cytochrome c and blue dextran. The present results indicate that the mucosa reduced dehydro-L-ascorbic acid by a cytosolic enzyme that uses NADPH as a hydrogen donor. Subsequent to precipitation by ammonium sulfate, the 55-70% fraction contains most of the reductase activity while consisting of only 17% of the cellular soluble protein. PMID- 2928351 TI - Effects of carbamylcholine and isoproterenol on electrolyte fluxes in perfused main duct of submandibular gland of reserpinized rat. AB - Administration of reserpine (RES) at a dosage of 0.5 mg/kg body wt, ip daily for 7 days was found to lower the dose of carbamylcholine and isoproterenol that alters sodium and potassium transport by cells of the main duct of rat submandibular gland. In the perfused main excretory duct of the submandibular gland of the RES rat, administration of carbamylcholine at a dosage of 1 microgram/kg body wt, inhibited net efflux of sodium (17%) and administration of isoproterenol at a dosage of 2 micrograms/kg body wt increased net efflux of sodium (20%); these drugs, at the same dosages, did not induce significant change in electrolyte flux of normal rat. At a dosage of 5 micrograms/kg body wt, carbamylcholine decreased net influx of potassium (15%) in the RES rat but was without effect on normal rat. Isoproterenol at the dosage of 5 micrograms/kg body wt significantly inhibited net influx of potassium in both the RES rat and normal rat. The data suggested that the duct cells developed supersensitivity to sympathomimetic and parasympathomimetic stimulation after chronic RES treatment. PMID- 2928352 TI - Dietary zinc deficiency decreases plasma concentrations of vitamin E. AB - Experiments were conducted to examine the effects of dietary zinc (Zn) upon plasma vitamin E (E) concentrations to test the hypothesis that there may be a significant dietary interaction between these two nutrients. Weanling female Sprague-Dawley rats were fed diets that were (i) Zn-deficient (less than 0.9 micrograms Zn/g diet) ad libitum; (ii) Zn-adequate (50.9 micrograms Zn/g diet), pair-fed to the Zn-deficient group; and (iii) Zn-adequate (50.9 micrograms Zn/g diet) ad libitum. Plasma E in Zn-deficient animals (4.02 +/- 1.20 micrograms/ml) was significantly reduced (P less than or equal to 0.05) compared with results in both Zn-adequate pair-fed (9.21 +/- 0.70 micrograms/ml) and Zn-adequate ad libitum-fed (9.47 +/- 0.90 micrograms/ml) animals. Zn deficiency in this model system also resulted in significant (P less than or equal to 0.05) reductions in femur and plasma Zn concentrations as well as in plasma retinol, plasma triglyceride, and plasma cholesterol concentrations. Plasma albumin and total plasma protein concentrations were normal in Zn-deficient animals. With dietary Zn deficiency, the decrease in plasma E appeared to be out of proportion to associated decreases in plasma triglyceride and plasma cholesterol concentrations. Since E is associated with plasma lipoproteins, these data suggest that lipid and/or E malabsorption may be a consequence of Zn deficiency. In response to increased dietary intake of E, increments of plasma E were lower in Zn-depleted than in Zn-adequate, pair-fed animals. These findings suggest that dietary Zn deficiency possibly may increase the nutritional requirement for E necessary to maintain adequate plasma concentrations. PMID- 2928353 TI - In vivo calvarial bone cell responses to dietary perturbations and the implications for mineral homeostasis. AB - Calvariae from small animals have been an important source for in vitro studies of bone. However, few in vivo studies have been undertaken on quantitative cell changes in calvariae. In the present study of mineral perturbations, rats were first deprived of calcium. After 18 days endosteal osteoclasts and nuclei/osteoclast in the parietal bone had increased 120% (P less than 0.001) and 26% (P less than 0.001), respectively, the marrow space had increased 141% (P less than 0.001), and the bone area experienced a 49% decrease (P less than 0.001). This thinning and weakening of the calvaria was accompanied by a compensatory increase in the number of endosteal osteoblasts (297%, P less than 0.001). These rats were then replenished with calcium, and after 14 days the number of endosteal osteoclasts had decreased to 86% (P less than 0.001) below the control and the endosteal surface was almost completely covered by osteoblasts (866% above the control, P less than 0.001). Bone area was increased by 51% (P less than 0.01). Similarly, in calcium-deficient rats in the tibial diaphysis at the fibular junction, the number of endosteal osteoclasts and the medullary space increased 1606% (P less than 0.001) and 63% (P less than 0.001), respectively, which were accompanied by a 32% decrease (P less than 0.001) in cortical bone area. After calcium replenishment, most endosteal osteoclasts in the tibial diaphysis disappeared from the endosteal surface and were replaced by osteoblasts (increased 487%, P less than 0.001). These results indicate that changes in bone cell activity in response to calcium deficiency are similar in calvariae and long bones, and that mobilization of calcium from the calvaria during calcium deficiency occurs at the expense of the protective action of the calvaria. Therefore, long bones as well as membranous bones are apparently important for the maintenance of mineral homeostasis. PMID- 2928354 TI - Oxygen consumption by portal vein-drained organs and by whole animal in conscious growing swine. AB - A method was developed to measure simultaneously the O2 consumption (VO) by the whole animal and by the hepatic portal vein-drained organs (PVDO), including the gastrointestinal tract, spleen, and pancreas in conscious 3.5- to 4-month-old swine. The method was used to determine (i) the effect of feeding on hepatic portal vein blood flow rate (Qpv) and VO by PVDO and by the whole animal, and (ii) the significance of PVDO on the oxidative demand in the pig. Chronic cannulas were placed in the hepatic portal vein, carotid artery, and ileal vein. The Qpv was determined by an indicator dilution technique employing continuous constant infusion of 1% p-aminohippuric acid into the ileal vein. The VO2 by PVDO was estimated by multiplying Qpv by arterial-portal vein O2 difference measured with an arterial-venous O2 difference analyzer connected to the carotid artery and portal vein cannulas. Whole animal VO2 was measured with an open circuit indirect calorimeter. In seven pigs (3.5- to 4-month-old, 37.4 +/- 0.8 kg) trained to be fed once daily, feeding (1.2 kg of feed mixed with 1.2 liter of H2O) caused postprandial (6 hr) Qpv to increase more than 34 +/- 15% above the preprandial value of 34.5 +/- 4.2 ml.min-1.kg-1 body wt. The postprandial VO2 by PVDO was elevated more than 46 +/- 12% above the value of 1.52 +/- 0.20 ml.min 1.kg-1 body wt observed during the preprandial period. Whole animal VO2 increased 45 +/- 9 and 33 +/- 7% above the preprandial value of 6.23 +/- 0.57 ml.min-1.kg-1 body wt for the first 6 hr and the 7 to 12 hr after feeding, respectively. Although PVDO represent only 5% of body weight, they used 25% of whole body VO2. The study clearly illustrates the significance of PVDO on the whole animal oxidative demand in conscious growing swine. PMID- 2928355 TI - The effect of aging on glutathione and cysteine levels in different regions of the mouse brain. AB - A general glutathione (GSH) deficiency occurs in many tissues of the aging mouse. However, there is no information on GSH in the aging brain even though it has been involved in a number of neurobiologic reactions. To this end, C57BL/6 mice, 3-31 months old, representing the growth, maturation, and aging periods of the life-span were studied. Brain cortex, hippocampus, and stem samples were dissected, processed, and analyzed specifically for reduced and oxidized glutathione (GSH, GSSG) and cyst(e)ine using high performance liquid chromatography with dual electrochemical detection. The GSH content of each brain region varied in the order brain cortex greater than brain hippocampus greater than brainstem. However, the GSH profiles of all regions were the same through the life-span, namely, high values during growth dropping to a maturation plateau and then decreasing 30% during aging. In contrast to GSH, the order of cysteine levels was brain cortex less than brain hippocampus less than brainstem and no life-span changes occurred in any region. In addition, the brain GSSG and cystine contents of all regions were very low and did not change during the life-span. Thus, the GSH loss was not accountable by oxidation to GSSG or degradation to cyst(e)ine. Altogether these results demonstrated a GSH deficiency in brain tissues of aging mice like that found previously in other tissues. These findings suggest an increased susceptibility of the aging brain to oxidative damage. PMID- 2928356 TI - Paracetamol: a bitter pill. PMID- 2928357 TI - Wound cleansing--which solution? PMID- 2928358 TI - Violence: is enough being done to protect you? PMID- 2928359 TI - Establishing a nurse coordinated diabetic review clinic. PMID- 2928360 TI - What makes the ideal community unit? PMID- 2928361 TI - Intravenous therapy in fluid and electrolyte imbalance. PMID- 2928362 TI - Communication can help ostomists accept their stoma. PMID- 2928363 TI - Britain's 'youngest' counties offer plenty of nursing choice. PMID- 2928364 TI - Nursing overseas offers an ocean of opportunities. PMID- 2928365 TI - District nursing--a self directed community role. PMID- 2928366 TI - Molecular and cellular mechanisms of septic shock. Proceedings of a conference. Bethesda, Maryland, February 29-March 1, 1988. PMID- 2928367 TI - Effect of macrophage inhibition in carrageenan- and D-galactosamine-induced sensitivity to low-dose endotoxin. PMID- 2928369 TI - Oncogene expression: a new horizon in the study of sepsis. PMID- 2928368 TI - Alterations in splenic and hepatic protein kinase C in sepsis and chronic endotoxemia. PMID- 2928370 TI - Altered membrane fatty acid composition and increased thromboxane A2 generation in platelets from patients with diabetes. AB - Lipid composition of platelet membranes and thromboxane A2 (TxA2) generation by platelets were investigated in 42 diabetic patients (14 with macroangiopathic complications, 10 with microangiopathy and 18 without vascular complications) and in 42 clinically healthy subjects of similar age. All subjects were on a similar dietary regimen and the adherence to diet was checked by analysis of red blood cell lipids. Platelets from all groups of diabetic patients produced increased amounts of TxA2 than platelets from controls (at least p less than 0.01) and patients with macroangiopathy (p less than 0.01). Platelet cholesterol and total platelet phospholipids were higher in patients with macroangiopathy, while the relative percentage of the different phospholipid fractions in platelet membrane and their saturated and unsaturated fatty acids were similar in the different groups. Arachidonic acid (AA) content in phosphatidylcholine (PC) was found to be significantly higher in diabetic patients than in controls (at least p less than 0.005). Moreover patients with macroangiopathy had higher AA (p less than 0.001) and lower eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) levels in PC (p less than 0.001) than the other groups of patients and controls. PMID- 2928371 TI - Prostaglandin E2 alters the metabolism of labelled glucose in uteri isolated from ovariectomized rats. Effects of 17-beta estradiol and indomethacin. AB - The effects of prostaglandins (PGs) E1, E2 and F2 alpha on the oxidation of labelled glucose in uterine strips from ovariectomized rats, were explored. Moreover, the influences of in vivo estrogenization of spayed rats and the presence in vitro of indomethacin (10(-6)M) on labelled glucose metabolism by isolated uteri, were also determined. PGE2 (10(-7)M), but not PGE1 or PGF2 alpha, enhanced significantly the formation of 14CO2 from U14C-glucose in uteri from spayed rats. After the injection of 17-beta estradiol to castrated animals prior to sacrifice the three PGs augmentated in vitro uterine glucose metabolism. In uterine strips from spayed non-estrogenized rats incubated with indomethacin, only PGE2 (10(-7) and 10(-6) M) incremented the formation of 14CO2 from labelled glucose, whereas PGE1 and PGF2 alpha were devoid of action, whereas in uteri from ovariectomized-estrogenized animals also incubated with indomethacin, PGE1, PGE2 and PGF2 alpha enhanced significantly the metabolism of labelled glucose, as was observed in the absence of indomethacin. However, in the presence of indomethacin the magnitude of the stimulation evoked by PGs in vitro was 3 to 4 times greater than without the inhibitor of the cyclo-oxygenase. The role of estradiol modulating the actions of PGE2 and PGF2 alpha on uterine glucose metabolism and possible reasons subserving the influence of indomethacin incrementing the effects of PGs on glucose oxidation in uteri from spayed-estrogenized rats, are discussed. PMID- 2928373 TI - Self-referencing subtractive angiography by modified stimulated echo in magnetic resonance imaging. AB - In magnetic resonance imaging, the modified stimulated echo sequence (MSTE) method significantly reduces the signal from stationary nuclei. This sequence was successfully applied to transverse imaging, improving the contrast of moving materials. With the results reported here, it will be shown that projective angiography using MSTE is also feasible without the usual subtraction of two separated images. Another advantage is selectivity with respect to velocity. PMID- 2928372 TI - Modulation of renal hemodynamics by renal eicosanoids during vasopressor infusions in man. AB - Pressor doses of norepinephrine (NE) (n = 8) and angiotensin II (A II) (n = 5) were infused in normal volunteers to determine whether the systemic administration of vasopressor hormones influence renal eicosanoid production and whether, in turn, the eicosanoids produced could modulate renal hemodynamics and electrolyte excretion. At the doses administered, both pressor substances induced the expected rise in blood pressure, a significant decrease (P less than 0.05) in renal blood flow and a proportionally smaller fall in glomerular filtration rate, resulting in a consistent augmentation in filtration fraction. Fractional sodium excretion was concomitantly reduced. NE infusion produced only slight modifications in urinary prostaglandin (PG)E2, 2,3-dinor-6-keto-PGF1 alpha and thromboxane (TX)B2, while urinary 6-keto-PGF1 alpha and PGF2 alpha were increased by 38% and 176% respectively. The increase in urinary 6-keto-PGF1 alpha (the non enzymatic degradation product of PGI2, predominantly of cortical origin) was proportional to the level of circulating NE (r = 0.78, P less than 0.05) and to the renal vascular resistance (r = 0.85, P less than 0.01), suggesting an immediate compensatory role for PGI2 in response to the NE-induced pressor stimulus. The renal production of PGE2 and PGF2 alpha (predominantly medullary) was inversely correlated with the filtration fraction: the greater the increase in PGE2 and PGF2 alpha the lower the elevation in filtration fraction or the decline in renal blood flow upon NE administration. All infusion variably stimulated the renal eicosanoid production: PGE2, 41%; PGF2 alpha, 102%; 6-keto PGF1 alpha, 38%; 2,3-dinor-6-keto-PGF1 alpha, 38%; and TXB2, 25%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2928375 TI - Abstracts of proceedings: IPSM/HPA 5th annual conference. Institute of Physical Sciences in Medicine. Canterbury, 14-16 September 1988. PMID- 2928374 TI - An extension of the three-zone model to predict depth of tissue damage beneath Er:YAG and Ho:YAG laser excisions. AB - Pulsed lasers such as Er:YAG and Ho:YAG with outputs at mid-infrared wavelengths emit radiation which may be transmitted by fibre to a treatment site. The thickness of soft-tissue damage beneath excisions made by these lasers is predicted using an extension to a model previously devised for CO2 laser radiation. The minimum achievable thickness occurs at a water absorption peak and at such high irradiance that heat cannot diffuse significantly compared with the radiation penetration depth. This minimum thickness is estimated to be in the order of 10 microns for the Er:YAG laser. PMID- 2928376 TI - A direct comparison of water calorimetry and Fricke dosimetry. AB - Considerable effort has been devoted to measuring the absorbed dose to water using water calorimetry. Most of these efforts have been hampered by a lack of adequate knowledge of the heat defect of water. We argue that there is now sufficient information to establish with considerable confidence the heat defect of high-purity water containing various dissolved gases. For the present work we used water saturated with a 50/50 mixture of H2 and O2 gases, for which the heat defect is calculated to be -2.1%. As a test of this assignment, we have compared the absorbed dose to water as measured using water calorimetry with that obtained from Fricke dosimetry. The water calorimeter consisted of a small sealed vessel containing 100 ml of stirred water saturated with a 50/50 mixture of H2 and O2 gases. It was irradiated with 20 MV x-rays at a dose rate of about 0.4 Gy s-1. The same vessel was then filled with Fricke dosemeter solution, and irradiated under identical conditions. Our Fricke dosimetry is based on the Svensson and Brahme value of epsilon G (3.515 x 10(-3) 1 cm-1 J-1) and agrees to within 0.2% with the dose to water for 60Co gamma-rays obtained via graphite calorimetry. We find that for 20 MV x-rays, the dose to water determined by water calorimetry is 1.006 +/- 0.004 times the dose determined by Fricke dosimetry. Within 0.6(+/- 0.4)%, this result supports the calculated heat defect of -2.1% for water saturated with a 50/50 mixture of H2 and O2 gases. PMID- 2928377 TI - Ferrous sulphate gels for determination of absorbed dose distributions using MRI technique: basic studies. AB - Two gels have been found to be suitable to load with ferrous sulphate solution. In these soft tissue equivalent phantoms, the absorbed dose distribution can be measured after irradiation in clinically used MR imaging equipment. The present studies were carried out using a 0.25 T NMR analyser without imaging properties. A ferrous sulphate solution, 0.05 M with respect to sulphuric acid, can be gelled with 4% gelatin to give a dosemeter which has a response which is linearly correlated (r = 0.998) with the absorbed dose in the interval 0-40 Gy. Ferrous sulphate solution can also be gelled with 1% agarose, but this gel has to be purged with oxygen to obtain a linear relationship (r = 0.997) in the same absorbed dose interval. The ferrous sulphate loaded gels have a sensitivity which is a factor of 2.2 or 4.0 times higher for gelatin and agarose, respectively, than the ordinary dosemeter solution. Because the standard deviation of background measurements is higher for the gels than for the dosemeter solution, the minimum detectable absorbed dose is about the same, or 1.0 Gy, for the two gels and the dosemeter solution. The sensitivity of the ferrous sulphate loaded gels shows no dependence on dose rate if the mean dose rate and the absorbed dose per pulse are within the limits normally used by accelerators for radiotherapy. PMID- 2928378 TI - Investigation of factors which lead to the background in the measurement of nitrogen by IVNAA. AB - A major problem in the measurement of nitrogen in the body by in vivo neutron activation analysis is the size of the background. Investigations show that random summing of gamma rays in the range 4-7 MeV is a major contributor. By direct comparison, 252Cf is shown to be a better neutron source than Pu-Be in this regard. Data are presented on the contribution to the background of water and chloride in the body. PMID- 2928379 TI - A simple calibration of a shadow shield counter for the measurement of total body potassium in critically ill patients. AB - A shadow shield counter has been built for the determination of total body potassium (TBK), based on the detection of the 1.46 MeV gamma rays emitted by the naturally occurring radioisotope (0.01%) 40K. Simple calibration procedures have been adopted which do not require administration of 42K to the subject. Self absorption effects of gamma rays have been taken into account by monitoring the activity of 40K per gram of potassium as a function of weight. All activity measurements, either during calibration or of a subject, include background in the spectral band covering the full width at half maximum (FWHM) of the 40K photopeak. The overall precision for determining the TBK was in the range of 1.8 3.0%. PMID- 2928380 TI - Effective energy resolution and scatter rejection in nuclear medicine. AB - All available imaging devices in nuclear medicine have finite energy resolution. This leads to inclusion of scattered radiation, which in turn degrades the image quality. Different scatter correction schemes therefore try to eliminate the effect of scattered radiation. On the other hand, improvement of the camera's intrinsic energy resolution would reduce the amount of detected scattered radiation as well. A simple model was developed in order to simulate the influence of the energy resolution on the camera response. It is shown that improvement of the energy resolution and scatter correction schemes have a similar effect on the point spread function. On this basis, it is suggested that 'effective energy resolution' be used as a new measure for the effectiveness of scatter correction schemes. As an example, this is done for energy-weighted acquisition (EWA), a scheme wherein each event contributes imaging information according to a real-valued, energy-indexed weighting function. PMID- 2928381 TI - Local energy deposited for alpha particles emitted from inhaled radon daughters. AB - An analytical method has been developed to calculate the local energy deposited by alpha particles emitted from radon daughters deposited on the mucus surface in the lung airways. For the particular cases of 218Po (Ra A) and 214Bi (Ra C'), microdose spectra have been evaluated in test spheres of 1 micron diameter which were taken to lie within airways of diameters 18,000, 3,500 and 600 microns. In each case, the contributions of the near and far wall were computed separately. The average microdosimetric parameters yF and yD have also been calculated. For the two smaller airways, yF and yD values were found to be about 110 and 135 keV microns-1 for 218Po and about 87 and 107 keV microns-1 for 214Bi respectively. The corresponding values were about 10% higher for the largest airway. PMID- 2928383 TI - Compton spectroscopy in the diagnostic x-ray energy range. I. Spectrometer design. AB - The optimal design of a Compton spectrometer for measuring photon energy spectra from x-ray tubes in a clinical laboratory is analysed. The demands are: (i) coherent and multiple scattering distort the measurements and must be avoided; (ii) the measuring time should be as short as possible to avoid unnecessary wear on the x-ray tube; and (iii) the impairment in energy resolution due to the scattering geometry should be kept minimal. A scattering angle of 90 degrees is advocated. Scatterers (of low-atomic-number material) in the shape of long circular rods (0.5-4 mm diameter, 20-40 mm long) are preferable to scattering foils. Use of a short focus-scatterer distance (approximately 200 mm) is to be preferred compared to using a large detector area (greater than or equal to 4 mm diameter) in order to establish a sufficiently high count rate in the detector. Short focal distances and a 90 degrees scattering angle are advantages in measuring energy spectra in the gantry of CT machines where the available space is limited. To limit the geometrical energy broadening to less than 1 keV, the spread in scattering angles of registered photons must not exceed 1-2 degrees for incident photon energies of 100-150 keV. PMID- 2928382 TI - Evaluation of the elastic behaviour of central venous PVC, polyurethane and silicone catheters. AB - Eighty used and 20 new silicone, polyurethane and polyvinylchloride central venous catheters were tested to establish the Young's modulus and the bending stiffness of the catheters and their introducers. The catheters were subjected to longitudinal traction forces and their lengthening measured. Young's modulus and the geometric moment of inertia were then calculated. It is shown that polyurethane catheters show least variation in their elastic characteristics, and that silicone catheters offer least resistance to bending and do not change their elastic properties after use. All catheters were equally unlikely to cause thrombus production if this is related to excessive bending stiffness. PMID- 2928384 TI - Compton spectroscopy in the diagnostic x-ray energy range. II. Effects of scattering material and energy resolution. AB - The overall performance of a Compton spectrometer and, in particular, its energy resolution are investigated both experimentally and theoretically for different scattering materials. Using low-Z (less than or equal to 8) scatterers of moderate sizes (scatterer diameter d less than or equal to 5 mm), there are negligible disturbances due to coherent and/or multiple scattering at 90 degrees scattering angle and photon energies above 20 keV. Two factors contribute to decreasing the energy resolution compared with that in direct measurements: (i) the velocity distribution of the electrons in the scatterer and (ii) the scattering geometry. Of these, (i) is dominant for photon energies less than or equal to 100 keV. The optimal scattering material is a metal of as low Z as possible, i.e. beryllium. However, polyethylene and lucite are normally sufficiently good scatterers. The scattering geometry may become the dominating factor decreasing energy resolution at high photon energies hv greater than or equal to 150 keV. PMID- 2928385 TI - Measurement of absolute energy spectra from a clinical CT machine under working conditions using a Compton spectrometer. AB - Absolute measurements of photon energy spectra (keV-1 sr-1 mA-1 s-1) from a clinical CT machine have been performed under normal working conditions (140 mA tube current) using a Compton spectrometer. The inaccuracy of the measured spectra is estimated to be +/- 6%, determined by uncertainties in dead-time corrections and in the parameters of the geometrical set-up. Absorbed doses measured in thermoluminescent LiF dosimeters agree within this uncertainty with calculated ones derived from measured spectra (80 kVp, 120 kVp and 140 kVp) and tabulated mass energy absorption coefficients for LiF. Comparison with tabulated energy spectra from the literature clearly shows the effect of the extremely small anode angle (7 degrees) in the CT machine (15 degrees and 17 degrees for the tabulated energy spectra). PMID- 2928386 TI - On the existence of an unambiguous solution in factor analysis of dynamic studies. AB - Achievement of an unambiguous solution in factor analysis of dynamic radionuclide studies depends on constraints reflecting the known properties of factors. The constraints should be tight enough to prevent ambiguity but sufficiently general in order to ensure the data-based derivation of factors. In dynamic scintigraphy, the non-negativity of factors is their essential property which is implied by the physical nature of measured quantities. Considering factors as the images of compartments in the distribution space of a radiopharmaceutical (i.e. performing the factor analysis in the spatial domain), a powerful additional constraint can be applied. This constraint is based on the presence of segments in the image matrix where the subtotal number of compartments is projected. Using this constraint, the existence of physiologically related unique solution in factor analysis can be proved providing the number of factors is chosen properly. PMID- 2928387 TI - A three-dimensional electron pencil-beam algorithm. AB - We describe the implementation of a three-dimensional electron-dose algorithm based on a Gaussian pencil-beam model. The algorithm calculates dose to an arbitrarily distributed set of points in a heterogeneous volume. Multiple non coplanar beams can be positioned relative to the volume. The algorithm consists of three basic components: (i) the transport of a pencil-beam through a heterogeneous volume, (ii) the evaluation of the pencil-beam fluence at a given depth in the volume in the presence of irregular fields, and (iii) the matching of points in the volume receiving a significant fluence contribution from a pencil-beam at a given depth in the volume and the calculation of dose to those points. An efficient point-matching algorithm reduces the computation time to the level of conventional two-dimensional implementations. The algorithm uses an optimised subdivision for irregular fields, and accurately predicts output factors for irregular fields placed between the final collimators and the patient. We show comparisons between the new algorithm and conventional two dimensional calculations using measurements and calculations for finite heterogeneities, irregular fields and output factors. PMID- 2928388 TI - Resolution of biexponential transverse relaxation in magnetic resonance imaging. AB - The accuracy in measurements of mono- and biexponential transverse relaxation processes with an MRI unit (0.5 T) was studied with a binary phantom. Comparison with spectrometer measurements (0.5 T) demonstrated that the imager underestimated the T2 values for monoexponential processes. Numerical resolution of biexponential processes also yielded underestimated relaxation times, but the resolution of a slow, constant component from faster components was relatively precise and consistent, provided the T2 ratio was above 2.5 in the T2 range 200 800 ms for a spin-echo sequence with 32 echoes. The effects of signal-averaging, strength of slice-selective gradient, single- versus multi-slice mode and repetition time were of little importance. In coronal slices a spurious biexponentiality occurred occasionally from monoexponential sources. The influence of stochastic noise was of minor importance compared to the effect of systematic noise. PMID- 2928389 TI - Sensitivity of LiF thermoluminescent dosemeters to 6-18 keV photons. AB - The sensitivity of thermoluminescent dosemeters (TLD) to 6-18 keV photons at six different effective energies was determined using an extrapolation chamber as a dosimetric standard. Photons having effective energies of 8.1, 9.2, 13.5, 13.8 and 18.0 keV were generated from an x-ray machine using appropriate kilovoltages and aluminium filters. Photons from an 55Fe source (6 keV) were also used to broaden the range of energies investigated. Observed sensitivities relative to 137Cs were found not to differ from unity with the possible exception of 6.0 keV photons. At 6.0 keV the sensitivity was found to be 0.83 +/- 0.5. PMID- 2928391 TI - Oxygen consumption during calisthenic exercise in women with coronary artery disease. AB - The purpose of this study was to compare the oxygen consumption (VO2) during calisthenic exercises in middle-aged women (aged 43-63 years) with and without coronary artery disease (CAD). Indirect calorimetry was used to measure VO2 in 15 healthy women and 15 women with CAD. Four exercises were performed for three minutes each before measurements of VO2 were taken. The exercises were 1) sitting knee extension, 2) standing hip flexion, 3) an upper extremity range-of-motion exercise, and 4) lateral trunk flexion. Using an analysis of covariance, no significant difference was found in VO2 between the two groups; however, there was a significant difference among the four exercises. Oxygen consumption was lowest for both groups during the knee extension and the lateral trunk flexion exercises; both groups demonstrated the highest levels for VO2 during the hip flexion exercise. This study provides evidence that the energy cost of these low intensity calisthenics is similar for healthy women and women with CAD. PMID- 2928390 TI - Radiation dose factors for alpha-emitters in osteons and some considerations on dose non-uniformity ratios and relative distribution factors. AB - Dose factors for locations within a tissue-filled cylindrical cavity bounded by an infinite medium of bone labelled with an alpha-emitter are calculated by means of a Monte Carlo procedure. The calculational approach is general and allows us to determine dose factors for specific distances or target volumes defined by concentric cylinders, as well as various source geometries including surface sources, buried surface sources, infinite and bounded volume sources, and also comprises plane (trabecular) surfaces as a limiting case. Values for the dose factors and the contribution of cross-fire traversals are calculated mainly for 239Pu and 226Ra and a typical Haversian canal diameter of 30 microns in beagles and 70 microns in humans. Also tables are given that allow dose factors to be derived for the relevant range of alpha-particle energies, diameters and target distances. The dose non-uniformity factors (local dose rate/average skeletal dose rate) for 239Pu are 27.2 in humans and 14.0 in beagles. The corresponding values for 226Ra are in the ranges 1.18-1.26 (humans) and 0.90-0.97 (beagles) for a 222Rn retention between 10-30%. The relative distribution factors 239Pu/226Ra are 21.5-23.0 for humans and 14.5-15.6 for dogs. General expressions for calculating non-uniformity factors and relative distribution factors are derived and implications are discussed in the light of some experimental findings. PMID- 2928392 TI - Obstetrics-gynecology in the physical therapy curriculum: a follow-up study. AB - This article reports the results of two questionnaire surveys conducted five years apart to evaluate the status and changes in obstetrics-gynecology (Ob-Gyn) units taught in physical therapy education programs. Sixteen new Ob-Gyn units were implemented in the five-year period between 1981 and 1986. Laboratory time for breathing and relaxation exercises decreased 50% between 1981 and 1986, whereas total hours for the Ob-Gyn unit remained the same. Fifteen respondents in the 1986 survey indicated gynecologic topic area content included reproductive anatomy, gynecological disorders, and evaluation techniques. The authors recommend increased laboratory time, development of Ob-Gyn internships, and further research. Threading Ob-Gyn concepts throughout the curriculum as well as having a concentrated Ob-Gyn unit are recommended. PMID- 2928393 TI - Intertester reliability of clinical judgments of medial knee ligament integrity. AB - The purpose of this study was to determine the intertester reliability of judgments based on tibiofemoral joint abduction (TFJA) tests of the medial collateral ligament (MCL). The TFJA tests were performed by three physical therapists on 50 patients with unilateral knee problems. The therapists used the techniques they normally use in clinical practice and tested TFJA with the knee in both 0 and 30 degrees of flexion. Three variables were evaluated: the amount of TFJA, pain elicited during the test, and the type of end-feel. When the test was performed with the subjects' knees in 0 degrees of flexion, the weighted Kappa value for judgments of motion was .06, the Kappa value for judgments of whether pain was elicited was .40, and the Kappa value for end-feel was .00. For the 30-degree test position, the weighted Kappa value for judgments of the amount of TFJA was .16, and the Kappa values for judgments of pain and end-feel were .33 and .38, respectively. The results suggest that judgments based on TFJA tests may not be reliable when taken in a clinical setting by physical therapists. PMID- 2928394 TI - Generalizability of grip strength measurements in patients with tennis elbow. AB - The purpose of this study was to determine the interrepetition and interoccasion generalizability of grip strength measurements in patients with the diagnosis of proximal extensor carpi radialis brevis tendinitis. Thirty-five consecutive patients (mean age = 44.5 +/- 8.6 years; mean duration of symptoms = 3.9 +/- 3.5 months) fulfilling the eligibility criteria participated in the study. Measurements of pain-free grip strength and maximum grip strength for the involved limb and maximum grip strength for the uninvolved limb were taken on two test dates within seven days of each other. We calculated the variation between measurements within a test session and the variation from one session to the next using generalizability coefficients based on the mean of the six measurements. The coefficients for interrepetition, interoccasion, and overall generalizability were .99, .97, and .96, respectively. The clinical implication of these findings is that the overall generalizability can best be enhanced by averaging grip strength measurements recorded from multiple test sessions rather than by increasing the number of repetitions during a single test session. PMID- 2928395 TI - Organizational socialization of physical therapists. AB - Organizational socialization is the process by which an individual becomes a member of an organization. It involves interaction between the employee and the organization during recruitment, hiring, and training and continues as the employee's role in the organization is defined and develops. The individual and the employee each have a set of expectations for the other; the extent to which these expectations are recognized, communicated, and combined in a mutually agreeable "psychological contract" can influence the eventual effectiveness, satisfaction, and longevity of the individual as an employee. The purpose of this article is to describe organizational socialization as it applies to the physical therapy setting. The author makes recommendations for management of the process. PMID- 2928396 TI - Low-load, prolonged stretch in treatment of elbow flexion contractures secondary to head trauma: a case report. AB - Joint contractures are a frequent complication of head trauma and often require extensive physical therapy intervention. Traditional methods of treatment, including passive stretching and range-of-motion exercises, have proven to be of limited benefit in contracture reduction. Low-load, prolonged stretch has been shown to be more effective than traditional methods of treatment in producing the desired elongation of connective tissue. A splinting device known as the Dynasplint is designed to provide this type of stretch. The purpose of this case report is to describe the application of the Dynasplint in the successful treatment of a patient with elbow flexion contracture secondary to head trauma. PMID- 2928397 TI - Our body of knowledge revisited. PMID- 2928398 TI - Reliability: consistency or differentiating among subjects? PMID- 2928399 TI - The reversed venous arterialized nerve graft in digital nerve reconstruction across scarred beds. AB - Conventional nerve grafts in complex digital injuries often yield poor results, particularly when placed in traumatized or avascular beds. Vascularized nerve grafts offer an option; experimental evidence suggests superior axonal regeneration across scarred beds with vascularized nerve grafts. We previously described a vascularized graft based on the dorsalis pedis artery--deep peroneal nerve "system." Reluctance to sacrifice this major artery, combined with the recent description by Townsend and Taylor and Gu, et al, of "reversed venous" arterialized nerve grafts, spurred us on to investigate the deep peroneal nerve- dorsalis pedis venae comitantes system. Fourteen neurovenous grafts were used in scarred or poorly vascularized beds for digital nerve reconstruction in 10 patients over a 4-year period. Graft length averaged 4.4 cm; interval from injury was 1 to 17 months. Sensory parameters of return included average static two point discrimination of 8.3 mm, moving two-point discrimination of 5.8 mm, and median Semmes-Weinstein monofilament appreciation of 2.83. Two patients received three vascularized grafts and three conventional grafts for adjacent nerve injuries in the same digit, serving as internal controls. In these patients, the vascularized nerve grafts returned mean static two-point discrimination values of 9.3 mm and moving two-point discrimination values of 6.7 mm. The conventional nerve grafts averaged static two-point discrimination of 14.3 mm and moving two point discrimination values of 10.3 mm. These differences imply enhanced axonal regeneration through vascularized nerve grafts. These data suggest that the reversed neurovenous graft may be the procedure of choice in secondary reconstruction of digital nerves across scarred beds or following injuries with poor soft-tissue vascularity, especially in those patients with cold intolerance. PMID- 2928400 TI - Speech results of the Zurich approach in the treatment of unilateral cleft lip and palate. AB - The purpose of this study was to describe perceptually the speech articulation, voice quality, and velopharyngeal competency of subjects with complete unilateral cleft lip and palate treated by the Zurich approach. The mean age of the 37 subjects was 10.5 years. Although only one subject had had secondary palatal management, no subject was rated as exhibiting a severe articulation or nasality problem. Subjects were rated as exhibiting adequate to marginal velopharyngeal competency 94.5 percent of the time, and the incidence of compensatory articulation errors was low. In comparison with other studies that evaluated the two-stage palatal repair, the Zurich approach appears to give the better results. The type of initial soft palate repair is probably the significant factor which contributes to the better speech of these subjects. PMID- 2928401 TI - Complications of Oriental blepharoplasty. AB - The complications of Oriental blepharoplasty are described according to their clinical appearance and anatomic findings at the time of surgery. The surgical correction of these complications is presented. A total of 42 patients with complications following blepharoplasty were treated. The types of deformities were categorized from their external appearance as asymmetry, retraction and ectropion, blepharoptosis, supratarsal depression, fading of the lid fold, and hemorrhage. The causes of each type of complication are identified according to the intraoperative findings, and the correlation between preoperative and intraoperative findings is explained. Correction of these complications follows identified guidelines, and the results were good to satisfactory. PMID- 2928402 TI - Use of contoured and stabilized conchal cartilage grafts for lower eyelid support: a preliminary report. AB - Lower lid stability can be affected by many conditions involving the lid directly, e.g. facial palsy, facial clefts, trauma, or tumors. Secondary stretching due to a poorly fitting orbital prosthesis can have the same effect. In 41 such eyelids, stability was obtained by inserting a large cartilage graft sutured to the tarsal plate and the infraorbital rim. Thirteen patients had tarsoconjunctival wedge resections, and 10 had lateral canthopexies performed at the same procedure. One graft was too small and was later replaced. There was one hematoma, which was evacuated. There were no other lid or visual problems. The follow-up is short, 21 months maximum, but so far the results are very satisfactory. PMID- 2928403 TI - Effectiveness of prophylactic mastectomy in the prevention of breast tumors in C3H mice. AB - The effectiveness of prophylactic mastectomy in the prevention of breast tumors was studied in spontaneous breast-tumor-forming C3H mice. Prolactin levels were assayed to determine if this hormone was related to the incidence of mammary tumors. Two-hundred and fifty-six 1-month-old C3H mice were divided into four groups (control, 1; sham surgery, 2; mammectomy 50 percent, 3; and mammectomy 100 percent, 4). At the time of sacrifice (0 to 1 year postoperatively) estrus cycles were determined, ventral skin (breast) and ovaries were removed for histology, and serum was collected for prolactin assays. Prolactin levels 24 hours postoperatively were significantly elevated (p less than 0.01) in groups 2 to 4 when compared with group 1. Six months postoperatively, prolactin levels were significantly higher (p less than 0.05) in mice with tumors compared with those without tumors in groups 3 and 4. There were no differences in tumor incidence between the four groups. At 12 months postoperatively, no differences in prolactin levels were noted, but group 2 animals had the highest incidence of mammary tumors (89 percent; p less than 0.01) when compared to groups 3 and 4. Mammary tumor incidence was not decreased by 50 percent or 100 percent mammectomy in C3H mice. Prolactin levels rose in response to surgery and/or anesthesia and remained elevated only in tumor-bearing mice who underwent mammectomy, an occurrence similar to that reported in humans. PMID- 2928404 TI - Physical, biomechanical, histologic, and biochemical effects of rapid versus conventional tissue expansion. AB - Clinical tissue expansion has been quite successful but takes 2 to 3 months. This study compares the effects of a conventional tissue expansion regimen of 6 weeks with an accelerated regimen of 2 weeks in the dog model, which is biomechanically similar to the human. In 22 dogs, the skin expanded 34.4 percent in the 2-week and 35.8 percent in the 6-week protocol, excluding stretch and recruitment. There was thinning of the panniculus carnosus in the 6-week group and otherwise no significant decrease in dermal thickness in either group. The biomechanical properties of elasticity and creep did not differ in expanded skin from both groups, while stress/relaxation mildly decreased from a control value of 53.5 percent to 48.8 percent in the 6-week group (p less than 0.05). Collagen activity was increased in both the 6-week and the 2-week groups (p less than 0.001) over nonexpanded skin, and immunohistochemical staining with a monoclonal procollagen antibody demonstrated collagen synthesis by dermal fibroblasts in both groups. We conclude that rapid tissue expansion did not demonstrate any deleterious effects when compared with a conventional regimen. PMID- 2928405 TI - Effect of the timing of tourniquet release on postoperative hematoma formation: an experimental animal study. AB - There is a controversy over when to release a pneumatic tourniquet after completing a hand surgical procedure. To study this controversy, we performed a standardized operation with tourniquet inflow occlusion on both lower legs of a series of rabbits. Total tourniquet time and the procedure performed, including intraoperative Bovie electrocautery of actual and potential bleeding points identified with 2.5 X loupe magnification, were identical on the two sides, except for the method of tourniquet release. On one leg, the tourniquet was released and all new bleeding points were controlled prior to wound closure. On the other leg, the tourniquet was released after the wound had been closed and dressed. Animals were injected with technetium-99m-labeled red blood cells and scanned to measure hematoma formation. Qualitatively, we observed more label in the leg whose tourniquet was released after wound closure in 17 of the 20 animals (p less than 0.005). Quantitatively, we also measured more mean label in the leg whose tourniquet was released after the wound was closed (p less than 0.001). Tourniquet release after wound closure was associated with greater hematoma formation. PMID- 2928406 TI - Legal, ethical, moral, disputable. PMID- 2928407 TI - Workaholics and editorials. PMID- 2928408 TI - The effects of simultaneous cleft lip and palate repair on craniofacial growth. PMID- 2928410 TI - Disposable battery-driven lighted retractor. PMID- 2928409 TI - Fire hazard of the ophthalmic cautery. PMID- 2928411 TI - Facial expression of schizophrenic patients and their interaction partners. AB - In his earlier works, one of the present investigators attempted to show that psychologically disturbed persons may be characterized by their tendency to induce their social partners to reveal relatively stable and constant leitmotivs, inclinations to react, emotions and fantasies; hence, it should be possible to describe psychological illnesses by means of the patient's specific interaction strategies (Krause 1988; Krause and Lutolf 1988). We assume that this process of induction is neither deliberate nor self-reflective. Inductive modes of behavior are viewed as part of an unconscious process of problem solving--a process, however, which is unsuccessful, since it is no longer appropriate to the reality of the adult patient. The present paper is part of a more comprehensive research project, the object of which is to account for these kinds of interactive strategies. PMID- 2928412 TI - The expression of primary affects in portraits drawn by schizophrenics. AB - In a psychiatric hospital setting, 15 patients under treatment for schizophrenia and 15 healthy persons were asked to draw (1) a human face, (2) another face that expressed their own feelings at that moment, and (3) afterward the facial expressions of rage, fear, disgust, joy, sadness and shame within a standardized egg-shaped face matrix. Both groups were matched for age, sex and education, and all drawings were coded independently. The schizophrenics drew fewer facial action units, and their facial drawings were more stereotyped than the control group's. Neutral faces without any affective expression were twice as frequent within the experimental group. According to Ekman and Friesen's table of emotion prediction, the accuracy was the same for both groups with the exception of sadness. Only 20% of the action units in the schizophrenics' sadness drawings were accurate compared to 51% in the control group. Based on observations during the drawing process, findings are discussed within the theoretical framework of cathexis defense as an attempt to reduce the impact of the affective stimuli the schizophrenics created themselves. PMID- 2928413 TI - A chronic psychotic: a longitudinal perspective. AB - Psychiatric illnesses involve complex interpersonal and biological processes that combine to produce certain clinical signs and symptoms of psychopathology on which psychiatric diagnostics are based. Nevertheless, the clinical presentation of some psychiatric disorders may vary from patient to patient or at different points in time on the same patient. The following case history serves to underscore the importance of the multi-axial approach in combination with longitudinal follow-up when an attempt is made to understand fully complex individuals. In particular, this case involves, at the minimum, the complex interweaving of a psychosis not easily subsumed under either pure schizophrenia or pure affective disorder together with substance abuse. It is the analysis of the serial unfolding of psychopathology that the authors feel will lead to a more comprehensive and better diagnostic formulation of an individual patient. PMID- 2928414 TI - Commentary on Gracia et al.: diagnostic entity or dynamic processes? AB - The case of Mr. G is a fascinating and beautifully presented, although sad, history of a patient. The clarity of the presentation and the discussion are particularly impressive in this example of the use of longitudinal data for descriptive diagnosis and conceptualization. The report exemplifies current trends in descriptive psychiatry, which focus on diagnosing an illness as a whole. The illness itself is considered a relatively static entity, even if it includes changes within its course. From this perspective, longitudinal data provide information for deciding what type of illness is being described. In my commentary, I would like to focus on a different way of using longitudinal data from that employed by the authors--a different type of longitudinal perspective, one that does not have the primary goal of defining a type of disorder diagnostically. I would like instead to focus on understanding this patient in terms of longitudinal processes rather than as someone afflicted with a persisting diagnostic entity. Attention to longitudinal processes can raise different questions and suggest what further information would be needed to understand these processes and plan optimal treatment. This more dynamic approach to understanding processes is not mutually exclusive with the static approach to diagnosis, but the two orientations provide very different perspectives on assessment, conceptualization and treatment. PMID- 2928415 TI - Attitudes of psychiatrists toward diagnostic options and issues. AB - Debate regarding the control of mental health services has marked the mental health scene for several decades. The debate continued and broadened, however, with the publication of DSM-III. The ubiquitous use of that diagnostic system for third-party reimbursement led some mental health professionals to call attention to the likely possibility that whoever controls diagnosis will also control mental health (O'Keefe 1980). This study sought to gather attitudinal information on psychiatrists' views regarding DSM-III, alternative nosological models, selected adjunct issues related to the medical model and mental illness concepts, and other professional concerns. PMID- 2928416 TI - A model of perceptual classification in children and adults. AB - The developmental trend from overall-similarity to dimensional-identity classifications is explained by a quantitative model. I begin with the assumption that objects are represented in terms of constituent dimensions and that the representation of objects changes little with development. Given this assumption, the model has three major parts. First, the similarity between objects is a function of the combination of the constituent dimensional differences. I propose developmental change in the likelihood that dimensions are differentially weighted in the calculation of similarity. Second, the perceived similarities between objects are valued for the purpose of constructing classifications. I propose that similarities are valued more dichotomously with age, such that identity becomes increasingly special. Third, the valued similarities are used to choose the best classification of those possible. The model provides good qualitative fits to the extant data. Three experiments examining classifications in 2- to 8-year-olds and in adults support specific new claims of the model. The data and the model provide new insights about development, classification, and similarity. PMID- 2928417 TI - A straight path-to where? Reply to Butterworth and Hadar. AB - Butterworth and Hadar (1989) discussed my earlier article (McNeill, 1985) but assumed their own linear theory and overlooked my proposal for an internal dialectic of imagery and language. This has led them into a whole series of misinterpretations. PMID- 2928418 TI - On "stress-induced recovery of fears and phobias". AB - Jacobs and Nadel (1985) proposed a neurobiological theory to explain the etiology of phobias. Their theory, however, is based on questionable assumptions about clinical fears. The present article is a critique of these assumptions. PMID- 2928419 TI - Theoretical analysis of the cognitive processing of lexical and pictorial stimuli: reading, naming, and visual and conceptual comparisons. AB - This article reviews the research literature on the differences between word reading and picture naming. A theory for the visual and cognitive processing of pictures and words is then introduced. The theory accounts for slower naming of pictures than reading of words. Reading aloud involves a fast, grapheme-to phoneme transformation process, whereas picture naming involves two additional processes: (a) determining the meaning of the pictorial stimulus and (b) finding a name for the pictorial stimulus. We conducted a reading-naming experiment, and the time to achieve (a) and (b) was determined to be approximately 160 ms. On the basis of data from a second experiment, we demonstrated that there is no significant difference in time to visually compare two pictures or two words when size of the stimuli is equated. There is no difference in time to make the two types of cross-modality conceptual comparisons (picture first, then word, or word first, then picture). The symmetry of the visual and conceptual comparison results supports the hypothesis that the coding of the mind is neither intrinsically linguistic nor imagistic, but rather it is abstract. There is a potent stimulus size effect, equal for both pictorial and lexical stimuli. Small stimuli take longer to be visually processed than do larger stimuli. For optimal processing, stimuli should not only be equated for size, but should subtend a visual angle of at least 3 degrees. The article ends with the presentation of a mathematical theory that jointly accounts for the data from word-reading, picture naming visual comparison, and conceptual-comparison experiments. PMID- 2928420 TI - Disagreement between therapists and subsequent suicide of the patient. AB - Two cases of suicide are reported for clients whose treating therapists disagreed about treatment. Therapists treating depressed and suicidal clients should be aware of the dangers to the client should such disagreement occur. Therapists should work together to formulate a treatment plan that is in a client's best interest. PMID- 2928421 TI - Beliefs and inferences: a test of a rational-emotive hypothesis: 2. On the prospect of seeing a spider. AB - 96 subjects were asked to imagine that they were about to enter a room in which there may have been one or more spiders. They were also asked to imagine that (a) they either held a rational or an irrational belief about spiders, (b) they were about to enter the room either alone or with someone, and (c) that the room was either dark or light. Having absorbed their assigned role, the subjects were then asked to make inferences about various elements of their situation. The results supported the hypothesis that holding an irrational belief leads to more negative inferences. It was also found that the lighting conditions in the room and whether the subject was alone or with someone affected the negativity of the inferences made. In addition, there were several two-way and three-way interactions between the independent variables which indicated that entering a light room or being with someone else tended to moderate the negativity of inferences made by those holding a rational belief rather than the opposite, amplifying the negativity of inferences made by those holding an irrational belief. The results supported Ellis's (1985) recent formulation concerning the complex relationship between events and inferences (A), beliefs (B), and emotional and behavioral consequences of beliefs (C). PMID- 2928422 TI - Learning in mice selectively bred for high and low aggressiveness. AB - Male mice selectively bred for aggressiveness (TA) and nonaggressiveness (TNA) were compared on maze performance and passive avoidance behavior. The two lines performed the learning tasks in separate ways but the significant differences in performance were probably due to factors other than the brightness of one particular line. PMID- 2928424 TI - Peer relations and behaviors of adoptive children in residential treatment. AB - This study explored the peer relationships and behaviors of 17 adoptive children in a residential treatment center. Compared to a group of 17 nonadoptive children, the youngsters tended to be rejected more by peers and to be perceived as having greater attentional difficulties by child-care workers. PMID- 2928423 TI - Relation of perceived health with psychosocial variables in elderly osteoarthritis patients. AB - Self-perceived health is related to physical health status and frequently assessed in research on elderly persons. The association of perceived health with sociodemographic, psychological, social functioning, and physical functioning variables was examined in 86 elderly osteoarthritis patients. Psychological well being (especially depression and anxiety), size of household, physical activity, and education were the most important predictors of self-perceived health (R = .70). Poor perceived health may suggest problems in elderly patients in several psychosocial areas, but good perceived health does not rule out psychosocial problems. PMID- 2928425 TI - Statistical versus clinical significance in research with the MMPI. AB - Some of the contradictions in psychological research may be attributable to failure to distinguish statistical from clinical significance. 82 articles in which the MMPI was the research instrument were analyzed to see how often the results reported as significant were in fact large enough to warrant such a conclusion. Articles were classified as to whether or not the clinical interpretations were consistent with the statistical results. Excluding articles in which data were insufficient to reach an independent conclusion, 54.90% of the articles presented conclusions of clinical significance that were not supported by the data, while 45.10% reported clinical results that were supported by the data. PMID- 2928426 TI - A causal model of mathematics performance in early adolescence: the role of sex. AB - Using path analysis, the present investigation was done to clarify possible causal linkages among general scholastic aptitude, academic achievement in mathematics, self-concept of ability, and performance on a mathematics examination. Subjects were 122 eighth-grade students who completed a mathematics examination as well as a measure of self-concept of ability. Aptitude and achievement measures were obtained from school records. Analysis showed sex differences in prediction of performance on the mathematics examination. For boys, this performance could be predicted from scholastic aptitude and previous achievement in mathematics. For girls, performance only could be predicted from previous achievement in mathematics. These results indicate that the direction, strength, and magnitude of relations among these variables differed for boys and girls, while mean levels of performance did not. PMID- 2928427 TI - Birth order, depression and suicide. PMID- 2928428 TI - Mental health of Iranian high school and college students. AB - The objectives of this study were to investigate the mental health of Iranian high school and college students with regard to sex differences and to compare the results with those from other countries. The sample included 159 high school students (79 boys, 80 girls) and 160 college students (80 boys, 80 girls). The Middlesex Hospital Questionnaire was used to measure free floating anxiety, depression, phobia, obsession, and somatization. Significant effects of group and sex were noted for phobia, but for depression only the main effect of group was significant. For other scales neither the main effects of group and sex nor their interactions were significant. Iranian college students showed more anxiety than their British peers. PMID- 2928430 TI - Reverse responding to the MMPI. PMID- 2928429 TI - Stability of WISC-R scores for a sample of learning disabled children. AB - The study was designed to assess the stability of WISC-R profiles of 36 learning disabled children given the WISC-R two times. The mean time between tests was 2.5 yr. The pattern reported for learning disabled children on Bannatyne's categories was evident for the group at both times, however, this pattern was not found for the majority of subjects. Analysis indicated a decrease over time in Verbal IQs, Full Scale IQs, and Bannatyne's Conceptual category, confirming previous findings. Possible reasons for the changes in scores are discussed. PMID- 2928431 TI - Effects of selected physical activities on health-related fitness and psychological well-being. AB - To determine the effects of participation in selected physical activities on scores of self-concept, body-cathexis and four items of health-related fitness, 88 women in university physical education service classes participated 3 hr. per week for 8 wk. in one of five activities (aerobic dance, jogging for fitness, swimming for fitness, life saving, and weight training). A total of 108 subjects participated in the study, with 20 students in health science classes serving as the controls. Few differences were noted between the activity groups and the controls on the posttest with pretest scores controlled. Specifically, joggers and aerobic dancers performed significantly more situps than did the controls, and joggers, aerobic dancers, weight trainers, and those in the lifesaving group displayed significantly greater flexibility on the sit and reach test than did the controls, on the posttest. None of the activity groups differed from the controls regarding self-esteem, body cathexis, body fat, or the step test scores at posttest. PMID- 2928432 TI - Adolescents' self-esteem measured as a specific score on the Strong-Campbell Interest Inventory. AB - Scores on the "Your Characteristics" section of the Strong-Campbell Interest Inventory (SCII) of 178 high school students (80 boys, 98 girls) were analyzed to determine if what we know about adolescents' self-esteem will predict scores. These adolescents obtained means similar to those of average adults. Implications for counselors are noted. PMID- 2928434 TI - Sex differences in behavioral reactions to provocation of anger. AB - The purpose of this study was to examine sex differences in behavioral reactions to provocation of anger. In a field study, 72 subjects recorded all anger arousing incidents for a 2-wk. period. Physical and Verbal Antagonism were found in more reports by men while Passive Consent was noted in more reports by women. For a laboratory study, 101 subjects responded to self-report scales of behavioral responses after exposure to an insulting letter. No sex differences were noted in subjects' self-reports of behavioral reactions. Variations in design are brought to bear in interpreting the findings. PMID- 2928433 TI - Effects of diazepam on a belief-updating task. AB - This study examined the effects of a minor tranquilizer, diazepam, on a cognitive task that involved the updating of beliefs. On this task, subjects are first asked to express their strength of belief in a hypothesis and then to update this on the basis of new evidence. Past research has shown that revision of beliefs can be affected by many variables including the strength with which the initial belief is held, whether new information is perceived as positive or negative vis a-vis the hypothesis, and the order in which evidence is processed. The purpose of this study was to assess whether a tranquilizer, diazepam, would affect the updating of beliefs, and specifically whether it would dampen the extent to which people revise their opinions. 12 healthy subjects participated in four experimental sessions, in which they received diazepam (0.14 mg/kg) or placebo and completed an updating task in which they received information in either of two orders, positive-negative or negative-positive. In each session, subjects saw a different experimental stimulus determined by a Latin-square design, and also completed pre- and postdrug mood questionnaires. Analysis showed order of presentation induced a recency effect similar to that obtained in previous studies, and the diazepam produced significant tranquilizer-like effects on self report questionnaires. However, the diazepam had no effect on the updating task. These findings indicate that previously reported order effects in the belief updating task are robust and unaffected by a drug that has known sedative and memory-impairing properties. PMID- 2928435 TI - Homophobia and attitudes about AIDS. AB - A random sample of 407 French Canadian adults responded to a questionnaire about perception of AIDS. Negative attitudes about AIDS are better predicted by homophobia than other measures as are attitudes about extramarital relations and attitudes abut adolescent heterosexuality. PMID- 2928436 TI - The Stress-Arousal Checklist as a measure of situational stress versus simple arousal. AB - The Stress-Arousal Checklist was developed as a self-report measure both of arousal and of the favorable or unfavorable appraisal of that arousal. Previous studies with the checklist showed differential sensitivity of the two subscales to experimental manipulations. In the present study, the convergent and discriminant validity were further explored by comparing scores with those on the State-Trait Anxiety Inventory-State. The results supported the validity of the two-factor structure. PMID- 2928437 TI - Developmental change in subjective probability during adolescence. AB - The developmental change in subjective probability during adolescence, an important period for establishing the probability concept, was investigated. 75 Japanese adolescents, from 12 to 23 yr. of age, were asked to make probability judgments for a lottery under 15 conditions. Analysis showed that with increase in age their subjective probability came closer to the objective probability. Discussion of these results took into consideration recent studies on the development of the concept of probability. PMID- 2928438 TI - Aggression and anxiety in day-care graduates. PMID- 2928439 TI - Hair mineral analysis: biochemical imbalances and violent criminal behavior. AB - Trace mineral analysis of human hair was utilized to determine whether violent and nonviolent criminals could be differentiated on the basis of concentrations of levels of major and trace minerals. 40 violent and 40 nonviolent inmates from a prison population were selected for study. 27 mineral levels were analyzed and a discriminant function analysis correctly classified 86% of the violent and 78% of the nonviolent inmates. The results lent support to the hypothesis that significantly different levels of trace minerals could be found between the two groups. PMID- 2928440 TI - The police stress survey: reliability and relation to job satisfaction and organizational commitment. AB - The 1981 Police Stress Survey of Spielberger, Westbury, Grier, and Greenfield was administered to 99 metropolitan and suburban police officers. Internal consistency reliabilities were in the .90s for both the total scale and two subscales which measure administrative/organizational and physical/psychological stressors. The administrative/organizational, but not the physical/psychological, subscale was significantly related to measures of job satisfaction and organizational commitment. PMID- 2928441 TI - Comparison of described empathic and nominated empathic individuals. AB - A composite profile of "empathic individuals" was developed from adjectives checked on Gough and Heilbrun's Adjective Check List by 43 undergraduate students enrolled in a course on counseling. Individuals were nominated as empathic by the students who also completed the checklist. The composite profile was consistent with the Rogerian definition of empathy and Factor 3 (Sociability) of the check list. The profiles for the nominated sample and for the students did not differ significantly on 36 of the 37 scales but both differed significantly from the composite profile on 34 scales. PMID- 2928442 TI - Fear of death and religious belief. PMID- 2928443 TI - Depression, learning disability, and school behavior problems. AB - It is possible that recurrent depression (primary affective illness) is the most significant variable related to school problems of a behavioral nature in children manifesting developmental specific learning disabilities. The association of school problems and depression was investigated at a private school for children with developmental specific learning disabilities. These children were of normal intelligence and were free of primary conduct or thought disturbances. Prior to entering school, 95% of the students fulfilled criteria for developmental specific learning disabilities and 64% for depression with or without hyperactivity. Students manifesting no diagnosable behavioral condition prior to entrance continued to be relatively free of behavioral problems during their stay at school. Students with both depression and hyperactivity showed the most problematic behavior followed by students with depression without hyperactivity. PMID- 2928444 TI - Consumption of attention versus affect elicited by cognitions in modifying acute pain. AB - 40 subjects were randomly assigned to conditions of high pleasure, low pleasure, high anger, or low anger in a 2 x 2 (intensity x affect) design. Although subjects used highly intense cognitions more than less intense ones, pleasant cognitions produced higher tolerance for pressure pain. Modification of pain may be mediated by specific affect rather than intensity or consumption of attention. PMID- 2928445 TI - Comparing 16 PF scores for two groups of offenders. AB - The 16 PF scores for 678 male offenders in a diagnostic and receiving center were compared with scores for 891 male offenders in penal institutions by t tests for independent means. Significant differences were obtained for 13 of the 16 primaries included in the 16 PF. The Penitentiary group scored significantly higher than the Reception Center group on the primaries, A, I, L, M, O, Q1, and Q4. Conversely, the Reception Center group scored significantly higher than the Penitentiary group on the primaries, B, C, F, G, N, and Q3. PMID- 2928446 TI - Level of object representation and psychic structure deficit in obese persons. AB - The structural deficit and external regulation hypotheses of addiction state that addicts do not have adequate psychic structure with which to regulate painful affects internally. They instead use their drug of choice as an external regulator to self-medicate painful affects. This study tests whether the hypotheses can be applied to obese persons, for whom food may be the drug of choice. The level of object representation of 22 moderately obese and 24 normal weight subjects was compared using the Blatt Family Interaction Questionnaire. The mean level of object representation of both parents was lower for the obese subjects than for the normal-weight subjects. This finding supports the structural deficit and external regulation hypotheses of food addiction. PMID- 2928447 TI - The deterrent effect of executions on homicide. PMID- 2928448 TI - Influence of rock videos on attitudes of violence against women. AB - 144 undergraduate men viewed rock videos which contained content that was erotic violent, erotic-nonviolent, nonerotic-violent, or nonerotic-nonviolent. Exposure to nonerotic-violent rock videos resulted in significantly higher Adversarial Sexual Beliefs scores and ratings of negative affect. These and other findings are discussed in terms of Bandura's concept of emotional incompatibility and the frustration-aggression model. PMID- 2928449 TI - Differing sexual practices of men and women screened for HIV (AIDS) antibody. AB - This study describes the results of a survey of all persons screened for antibodies to the Human Immunodeficiency Virus (HIV) during a 3-mo. period at a county health department. Complete interviews and serologic analysis for antibodies to HIV using the enzyme-linked immunosorbent assay were obtained from all 43 persons. HIV antibodies, confirmed by Western blot assay, were present in 7 or 16% of the sample. Self-reported changes in sexual practices among the 27 seronegative homosexual men occurred prior to counseling and screening, but 9 seronegative women reported no change in high-risk behaviors. The number of black men and women screened were disproportionately smaller than their representation in the community. These findings suggest that stronger educational efforts are needed to disseminate information to women and blacks who are at risk for HIV infection. PMID- 2928450 TI - Validation of an MMPI short form with literate and illiterate patients. AB - An Improved Readability Form (IRF) of the MMPI was orally administered to 100 literate and 119 illiterate patients, and 140 literate patients were given the full MMPI with standard instructions. Profile comparisons of the MMPI with the IRF given to literates or extracted from the full MMPI yielded only small differences. The much larger differences in the IRF profiles of the illiterates were removed by controlling statistically for sex, race, age, and education. The IRF, when given to literate patients, was a good substitute for the full MMPI in predicting Brief Psychiatric Rating Scale scores. For the illiterates, the two most salient relationships with scores on the Brief Psychiatric Rating Scale were preserved, but several weaker associations were qualitatively altered. When the IRF is administered to illiterate patients, the pattern of clinical correlates may differ from those obtained with literate patients given the IRF or MMPI. PMID- 2928451 TI - Suicides at the casino. AB - Suicides occurring at casinos were examined and, in a sample of six, three appeared to be gambling-related, with the individuals killing themselves after losing large sums of money. PMID- 2928452 TI - Relationship between academic achievement and measured career interest: examination of Holland's theory. AB - The present study was designed to examine Holland's hypothesis that person environment congruence relates positively to academic achievement. The sample of 157 nontraditional premedical students completed Holland's Self-directed Search interest inventory. The students were enrolled in the Medical/Dental Education Preparatory Program, which is designed to increase the number of qualified applicants who are underrepresented in the medical profession. Using scores on Holland's inventory students were classified as congruent or incongruent. A cumulative grade point average and a science grade point average were calculated for each student. An analysis of variance supported Holland's Congruence achievement hypothesis. Congruent students did in fact achieve significantly higher cumulative GPA and science GPA than did incongruent students. Implications for counseling and academic advisement as well as further research are discussed. PMID- 2928453 TI - Narcissistic personality features and self-reported anger. AB - The relationship between anger and narcissistic personality characteristics was examined for 91 students in introductory psychology courses. 35 individuals high in narcissism reported greater verbally expressed anger. Males high in narcissism were more likely to express anger physically. Results are discussed in terms of DSM-III--R criteria for narcissistic personality disorder. PMID- 2928454 TI - The Krantz Health Opinion Survey: correlations with preventive health behaviors and intentions. AB - The Krantz Health Opinion Survey, a measure of treatment preferences, was administered to 124 college women who also completed the Multidimensional Health Locus of Control Scale and rated their own preventive health behaviors and intentions. Analysis confirmed previous findings of relations between the two scales, particularly the moderate negative correlation between the Krantz Behavioral Involvement Scale and Powerful Others Locus of Control. The Krantz scores also were correlated with demographic measures such as education and occupation of the head of the household. With the exception of low correlations with frequency of obtaining Pap tests and with intentions to engage in exercise, the Krantz scores were uncorrelated with preventive health behaviors and intentions. It may be that another variable such as health value moderates these associations. PMID- 2928455 TI - Effects of moral reconation therapy upon moral reasoning, life purpose, and recidivism among drug and alcohol offenders. AB - 40 incarcerated DWI offenders and 62 drug offenders who were treated with Moral Reconation Therapy were assessed with respect to levels of moral reasoning, their perceived purpose in life, and subsequent recidivism. Analysis showed that, as clients progress in the program, levels of moral reasoning and purpose in life increase significantly. Level of moral reasoning appears to increase with clients' completion of therapeutic steps. Preliminary recidivism data on 103 male and female inmate-clients who have participated in an aftercare program using the therapy appear encouraging. PMID- 2928456 TI - Measuring consultation judgment-making ability: further development of the Consultation Judgment Inventory. PMID- 2928457 TI - Laboratory stress testing to assess real-life cardiovascular reactivity. AB - Thirty-six normotensive adults received laboratory stress testing (mental arithmetic, short-term memory, isometric handgrip, cold pressor tests) and 24 hour ambulatory blood pressure monitoring on two work days separated by a month. Laboratory and ambulatory measures of cardiovascular reactivity had low test retest reliability. Increases in blood pressure during the memory and cold pressor tests were related to measures of reactivity obtained outside the laboratory (waking blood pressure variability, responses to home and work environments). However, the portion of ambulatory reactivity accounted for by laboratory reactivity was small. In the best case (r = 0.43), cold pressor diastolic pressure explained only 19% of diastolic pressure variability in the natural environment. Laboratory-ambulatory disagreement in reactivity was related to interindividual variability in physical activity on the day of ambulatory monitoring. PMID- 2928458 TI - Subjective symptomatology of asthma in an outpatient population. AB - Characteristics of subjective symptomatology of asthma were examined within a group of 132 adult asthma patients receiving medical care in a university-based, ambulatory clinic setting. Patients responded to 36 symptom descriptions or adjectives associated with asthma which were included in a modified version of the Asthma Symptoms Checklist (ASC). A principal components exploratory factor analysis was conducted and five factors were identified. The five factors measured 1) panic-fear, 2) airways obstruction, 3) hyperventilation, 4) fatigue, and 5) irritability. Psychometric properties of the factor scores were satisfactory. The reliabilities were high, standard deviations were large, and differences in factor mean scores conformed to clinical experience. Correlational analyses support the construct validity of the ASC, especially the panic-fear factor. An important outcome of this study was to verify the ASC factor structure in an outpatient setting. The ASC was confirmed as a valuable instrument for use in self-management programs for adults with asthma. The five ASC factors represent highly stable components of subjective symptomatology of asthma among diverse adult patient populations and geographical settings. PMID- 2928459 TI - Hostility and cardiovascular reactivity to stress in women and men. AB - The relationship of Cook Medley hostility scores (Ho) to blood pressure and heart rate reactivity was examined in 56 women and 56 men. Stress was elicited by an unsolvable anagram task that was described as easily solvable. Both men and women scoring high on Ho had greater blood pressure responses to the task. Those scoring high on Ho also reported more anger in response to the tasks, but anger was not associated with blood pressure reactivity. It was concluded that situations evoking suspiciousness and mistrust rather than anger may be necessary to elicit increased blood pressure reactivity among high Ho subjects. PMID- 2928460 TI - The Cook-Medley hostility scale: item content and ability to predict survival. AB - Previous studies have identified the MMPI-based Cook and Medley hostility scale (Ho) as a predictor of health outcomes. To achieve a better understanding of the construct measured by this scale, Ho items were classified on an a priori basis. Six subsets were identified: Cynicism, Hostile Attributions, Hostile Affect, Aggressive Responding, Social Avoidance, and Other. Study 1 examined the correlations of these subsets with scales of the NEO Personality Inventory in two samples of undergraduates. Good convergent and discriminant validity were demonstrated, but there was some evidence that items in the Social Avoidance and Other categories reflect constructs other than hostility. Study 2 examined the ability of the Ho scale and the item subsets to predict the 1985 survival of 118 lawyers who had completed the MMPI in 1956 and 1957. As in previous studies, those with high scores had poorer survival (chi 2 = 6.37, p = 0.012). Unlike previous studies, the relation between Ho scores and survival was linear. Cynicism, Hostile Affect, and Aggressive Responding subsets were related to survival, whereas the other subsets were not. The sum of the three predictive subsets, with a chi 2 of 9.45 (p = 0.002), was a better predictor than the full Ho scale, suggesting that it may be possible to refine the scale and achieve an even more effective measure of those aspects of hostility that are deleterious to health. PMID- 2928461 TI - A caution on the use of the MMPI K-correction in research on psychosomatic medicine. AB - The MMPI K scale is widely used to screen for invalid responses and to adjust substantive scale scores for defensiveness. In a normal volunteer sample, correlations of MMPI clinical scales and the Cook-Medley Hostility (HO) scale with self-reports and peer ratings on the NEO Personality Inventory (NEO-PI) were decreased rather than increased by K-correction. Similarly, in a medical sample, structured interview-based ratings of Potential for Hostility were better predicted by uncorrected HO scores than by K-corrected HO scores. Finally, in a prospective study of mortality among lawyers, uncorrected HO scores were a significant predictor of all-cause mortality; K-corrected scores were not. The data suggest that, under some circumstances, the K scale may measure substantive traits rather than defensiveness, and should be used and interpreted with caution. Its use is probably contraindicated for most research on psychiatrically normal subjects. PMID- 2928462 TI - Women and their husbands: mood and arousal fluctuations across the menstrual cycle and days of the week. AB - This study examined the relationship between biological (menstrual cycle) and social-contextual (day of the week) factors and psychological and physical events among nine women and their spouses. Employing P-technique factor analysis to identify consistent patterns in single-subject data over 90 days of reporting, two factors emerged: Negative Mood and Arousal. When these factors were compared over five phases of each woman's menstrual cycle, the only significant finding was that men's Arousal scores were significantly greater during their wives' menses phase compared to their follicular phase. Negative Moods decreased on weekends for both males and females, and females also showed a decline in Arousal on the weekend. The finding that our social factor (day of the week) accounted for more variability in subjects' reports than did our biological factor (the menstrual cycle) emphasizes the importance of considering biological events in the context of social structures and belief systems. PMID- 2928463 TI - Menstrual cycle abnormalities and subclinical eating disorders: a preliminary report. AB - Menstrual dysfunction is a common concomitant of anorexia nervosa and bulimia. Initial investigations emphasized the role of weight loss and lean/fat ratio in amenorrhea. Subsequent studies suggest a more complex interaction between eating disorders and menstrual status. However, in past investigations, menstrual abnormalities have been confounded with low weight. We conducted two studies to ascertain the prevalence of menstrual abnormalities in a group of women with subclinical eating pathology versus an age-, education-, and weight-matched group of normal controls. In Study I, 93.4% of the subclinical subjects reported a history of menstrual abnormality as compared to 11.7% of the normal controls. In Study II, 100% of the subclinical subjects, versus 15.0% of the controls, reported an abnormal menstrual history. These data suggest that menstrual dysfunction often occurs in women with abnormal eating attitudes but without weight loss or diagnosable eating pathology. Several hypotheses for this finding are proposed. PMID- 2928464 TI - MNA opposes proposed physicians assistants bill. PMID- 2928465 TI - Hypertrophy of cultured bovine aortic endothelium following irradiation. AB - The vascular endothelium is a vital multifunctional tissue which covers the entire luminal surface of the circulatory system. Loss of continuity of the endothelial lining normally results in cell migration and proliferation to make up for cell loss and to ensure that exposure of the thrombogenic subendothelium to platelets and clotting factors is minimized. We showed that ionizing radiation (400-3000 cGy) causes dose-dependent cell loss from confluent monolayer cultures of bovine aortic endothelium, which cannot immediately be compensated by cell proliferation. Within 24 h, the remaining attached cells undergo substantial somatic hypertrophy (evidenced by increased protein content, cell volume, and attachment area) but remain diploid. If cell loss is not excessive, monolayer continuity is restored within several days. Although reduced protein degradation may contribute, most of the protein accumulation is due to synthesis of new protein. Unlike endothelium, irradiation of smooth muscle cultures causes neither cell loss nor increased protein synthesis. Hypertrophy of irradiated endothelial cells appears to be a consequence of a proliferative stimulus (cell loss) in a population of cells which is unable to divide. It can be modulated by replating irradiated cells at different densities. We suggest that endothelial hypertrophy is an early vascular homeostatic response before clonal proliferation of surviving cells or repopulation by cells from outside of the irradiated field can compensate for cell loss. PMID- 2928466 TI - Oxygen enhancement ratio of fractionated regimens in vitro. AB - The oxygen enhancement ratio (OER) of proliferating and nonproliferating cells grown in vitro was measured using accelerated fractionated regimens. Irradiations were performed either twice daily or three times per day, with a minimum of 6 h between the consecutive fractions. The dose delivered was 2.3 Gy per fraction. Two significant observations were made: (i) the OER of accelerated fractionation regimens for proliferating cells is lower than that obtained from single-exposure experiments at 2.3 Gy (approximately 1.4 vs 2.4, respectively), while for nonproliferating cells it is approximately the same (2.3); (ii) the fractionated regimen does not spare proliferating cells irradiated under hypoxic conditions, and thus the fractionated survival curve lies below the single-exposure curve. For cells irradiated under aerobic conditions or for nonproliferating cells, irradiated under either hypoxic or aerobic conditions, the fractionated survival curve lies above the single-exposure curves as expected. PMID- 2928467 TI - Gamma radiation affects active electrolyte transport by rabbit ileum. II. Correlation of alanine and theophylline response with morphology. AB - The response of ileal segments isolated from rabbits to an actively transported amino acid and a secretagogue was evaluated following exposure to 10 Gy whole body gamma irradiation. The ability of ileal segments to respond to the actively transported amino acid, alanine, was not significantly diminished until 96 h postexposure. Decreased responsiveness to the secretagogue, theophylline, occurred earlier at 72 h. These effects did not appear to be accounted for by decreased food intake of irradiated animals alone. Examination of intestinal morphological changes with respect to these changes in electrolyte transport revealed that decreased amino acid transport coincides with loss of intestinal villi. Although a morphological correlate of decreased secretory response was not as striking as that for absorption, the theophylline response appeared to decline concomitant with the appearance of increased mitotic activity in the intestinal crypts. The results of this study indicate that, following a dose of 10 Gy, the inability of these tissues to respond to amino acids is due to a loss of mature villus absorptive cells subsequent to denudation of the intestinal mucosa. There appeared to be little impairment of cell membrane transport processes for alanine. In contrast, the decreased secretory response could not be correlated with the disappearance of any one cell type and perhaps results from increased proliferation in the crypts at the expense of differentiation. PMID- 2928468 TI - Quiescence in 9L cells and correlation with radiosensitivity and PLD repair. AB - The onset of quiescence, changes in X-ray sensitivity, and changes in capacity for potentially lethal damage (PLD) repair of unfed plateau-phase 9L44 cell cultures have been systematically investigated. The quiescent plateau phase in 9L cells was the result of nutrient deprivation and was not a cell contact effect. Eighty-five to 90% of the plateau-phase cells had a G1 DNA content and a growth fraction less than or equal to 0.15. The cell kinetic shifts in the population were temporally correlated with a developing radioresistance, which was characterized by a larger shoulder in the survival curve of the quiescent cells (Dq = 5.71 Gy) versus exponentially growing cells (Dq = 4.48 Gy). When the quiescent plateau-phase cells were refed, an increase in radiosensitivity resulted which approached that of exponentially growing 9L cells. Delayed plating experiments after irradiation of exponentially growing cells, quiescent plateau phase cells, and synchronized early to mid-G1-phase cells indicated that while significant PLD repair was evident in all three populations, the quiescent 9L cells had a higher PLD repair capacity. Although data for immediate plating indicated that 9L cells may enter quiescence in the relatively radioresistant mid G1 phase, the enhanced PLD repair capacity of quiescent cells cannot be explained by redistribution into G1 phase. When the unfed quiescent plateau-phase 9L cells were stimulated to reenter the cell cycle by replating into fresh medium, the first G1 was extended by 6 h compared with the G1 of exponentially growing or refed plateau-phase 9L cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2928469 TI - Relationship between energy status, hypoxic cell fraction, and hyperthermic sensitivity in a murine fibrosarcoma. AB - The energy status, radiobiological hypoxic cell fraction, and hyperthermic sensitivity of a spontaneous murine fibrosarcoma, FSa-II, have been evaluated as a function of tumor size. Tumors were evaluated over the size range of 70 to 800 mm3. The concentration of the high-energy phosphate reservoir creatine phosphate progressively decreased by a factor of 5 with increasing tumor volume, and was matched by an increase in creatine. The concentration of ATP also decreased with increasing tumor size, although this decrease was substantially less pronounced. The sum of ATP, ADP, and AMP did not vary with tumor size, suggesting that the necrotic fraction remained constant. The decrease in energy status occurred in parallel with an increase in the size of the hypoxic cell fraction and with increasing thermal sensitivity. The results suggest that energy status may be an important modifier of hyperthermic sensitivity in vivo and reflect tissue oxygen concentration. PMID- 2928470 TI - Relative biological effectiveness of tritiated water to gamma radiation for germ line mutations. AB - The relative biological effectiveness was determined using sex-linked recessive lethals induced in Drosophila spermatozoa as the biological effect. The sex linked recessive lethal test, a measure of mutations induced in germ cells and transmitted through successive generations, yields a linear dose-response curve in the range used in these experiments. A dose-response curve was determined from three exposures to tritiated water and three exposures to 60Co gamma radiation. The ratio of the slopes of these two response curves is 2.7 +/- 0.3, yielding a relative biological effectiveness that suggests the tritium beta particle is 2.7 times more effective per unit of energy absorbed in inducing gene mutations transmitted to successive generations than 60Co gamma radiation. The increase in relative biological effectiveness with higher linear energy transfer for tritium beta radiation strongly suggests that single-strand breaks are repaired by a nearly error-free repair mechanism. Ion tracks with a high density of ions (high linear energy transfer) are more efficient than tracks with a low ion density (low linear energy transfer) in inducing transmissible mutations, suggesting interaction among products of ionization. Since most transmitted mutations induced by ionizing radiation result from strand breakage, interaction probably occurs at this level with double-strand breaks being repaired by an error-prone mechanism yielding transmissible mutations. PMID- 2928471 TI - Measurement of DNA damage and cell killing in Chinese hamster V79 cells irradiated with aluminum characteristic ultrasoft X rays. AB - Chinese hamster V79 cells were irradiated with 1.487 keV aluminum characteristic X rays produced using a cold-cathode discharge tube. Under aerobic conditions a relative biological effectiveness (RBE) of 2.18 for cell killing in comparison to 250-kVp X rays was measured using cells grown in suspension and irradiated on membrane filters. DNA damage in the form of single-strand (ssb) and double-strand breaks (dsb) was measured using the filter elution technique. The aerobic RBEs are 1.64 for dsb induction and 0.49 for ssb induction, consistent with the view that dsb are more closely related to cell kill than ssb. A reduced oxygen enhancement ratio (OER) for cell killing was measured for Al-K X rays, but the OER for dsb induction was similar to that measured for 250-kVp X rays. A curvilinear relationship between dsb induction and dose is observed, similar to that seen for 250-kVp X rays. This agrees with the concept that ultrasoft X rays produce critical lesions similar to hard X rays but with a greater efficiency per unit dose. PMID- 2928472 TI - Protection by WR1065 and WR151326 against fission-neutron-induced mutations at the HGPRT locus in V79 cells. AB - The radioprotectors WR1065 and WR151326, each at a concentration of 4 mM, protect against cell killing and mutagenesis at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus in V79 Chinese hamster fibroblast cells exposed to fission-spectrum neutrons (mean energy of 0.85 MeV) from the JANUS reactor. Significant protection against neutron-induced cell lethality occurred only when the radioprotectors were present during irradiation; e.g., D0's and n's were 82 Gy, 1.27 for control cells; 97 Gy, 1.51 for WR1065-protected cells; and 120 Gy, 1.00 for WR151326-protected cells, respectively. Mutation induction by JANUS fission-spectrum neutrons was linear over the dose range tested giving rise to a mutation frequency of 109.3 x 10(-6)/Gy. In comparison with 60Co gamma rays (mutation frequency 8.7 X 10(-6)/Gy), JANUS neutrons, at a dose rate of 24 cGy/min, were over 12 times more effective in inducing HGPRT mutations. Both WR1065 and WR151326 afforded protection against the induction of mutants by neutrons, even when they were administered up to 3 h after irradiation; i.e., mutation frequencies were 40.9, 48.8 and 68.6 X 10(-6)/Gy for WR1065 present during, present immediately after, or added 3 h after irradiation, respectively; and 61.7, 47.8, and 68.5 X 10(-6)/Gy for WR151326 present at the same times. PMID- 2928473 TI - The relationship of increased nuclear protein content induced by hyperthermia to killing of HeLa S3 cells. AB - The role of a heat-induced increase in nuclear protein mass in killing of cells by hyperthermia was investigated jointly by two groups that had previously reported apparently conflicting results. A correlation between the fraction of HeLa S3 cells killed and the protein content of nuclei isolated immediately after heat exposure was found. This correlation held when thermal sensitivity was modified by the sensitizers 0.41 M ethanol and 5 mM procaine or by the protector 0.6 M glycerol. However, when the HeLa cells were made thermotolerant by a priming heat exposure of 15 min at 45 degrees C followed by 5 h at 37 degrees C, the correlation no longer held. At the 10% survival level a 1.27-fold greater nuclear protein content was observed in tolerant cells relative to nontolerant cells. Thus no general correlation between initial heat-induced nuclear protein mass changes and hyperthermic cell killing exists. When heated cells were returned to 37 degrees C, a time-dependent reduction in the protein content was observed in nuclei isolated after incubation for various times at 37 degrees C. This rate of reduction in nuclear protein content was found to be accelerated in the tolerant cells. Heat-induced changes in cell-cycle progression had no significant effects on the data obtained. It is concluded from the total data base that not only the absolute increment in nuclear protein mass must be taken into account but also the duration of the binding expressed in the rate of recovery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2928474 TI - Metabolism of tritiated water in the cell nucleus and intracellular substances of the rat. AB - Tritiated water was given to rats in single oral doses, and the cell fractions for each organ were prepared by ultracentrifugation for measurement of the concentration of tissue-bound tritium. The concentration of tissue-bound tritium reached a peak relatively soon after intubation, 1-4 days after administration. The initial concentration of tissue-bound tritium in liver and kidney was high in the mitochondrial and microsomal fractions but low in the nuclear and cytosol fractions. The initial tissue-bound tritium concentration in the brain was high in the mitochondrial and microsomal fractions but low in the nuclear and cytosol fractions. The initial concentration of tissue-bound tritium in the testes was high in the mitochondrial, microsomal, and cytosol fractions but low in the nuclear fraction. The half-life for the long component was larger in the nuclear, mitochondrial, and microsomal fractions of the brain than in the other organs according to an interorgan comparison of each fraction. As for the testes, the values for the mitochondrial and microsomal fractions were larger than those for the other organs. PMID- 2928475 TI - Induction of neoplastic transformation in C3H/10T1/2 cells by 2.45-GHz microwaves and phorbol ester. AB - C3H/10T1/2 cells were exposed to 2.45-GHz microwaves for 24 h and/or 1.5 Gy of 238-kVp X rays at 3.75 Gy/min. Transformation frequency and cell survival were measured with or without postirradiation addition of the tumor promoter tetradecanoyl-phorbol-13-acetate (TPA) at 0.1 microgram/ml. We previously reported (Carcinogenesis 6,859-864, 1985) an enhancement of transformation frequency when 10T1/2 cells exposed to a special sequence of microwaves and X rays were subsequently cultured in TPA. The same sequence of microwaves and X rays without promotion resulted in a transformation response similar to that induced by X rays alone. We now report statistically significant (at P greater than 0.999) enhancement of transformation response by TPA in cells exposed to 2.45-GHz microwaves (SAR = 4.4 W/kg). Microwaves alone had no effect on transformation. Plating efficiency and cell survival were not affected by TPA or microwave treatments. PMID- 2928477 TI - [An evaluation of the radiation similarity between soft biological tissue and a modified ferrosulfate dosimeter]. AB - On the basis of recent recommendations on soft biotissue composition and data concerning value of specific neutron kerma for a number of element atoms within the energy from thermal one to 29 MeV obtained were the values of electron density, effective atomic number and specific kerma of neutrons for soft biotissue and ferrosulphate dosimeter sensitized by benzoic acid. The data are proposed for practical use in radiobiological experiments. PMID- 2928476 TI - Quantitation of strand breaks in human DNA using 32P-Alu hybridization: application to exponential and plateau-phase cells. AB - A sensitive quantitation of DNA (0.2 to 10 ng) can be achieved using a 32P labeled Alu probe to hybridize human DNA spotted onto nylon membrane. This allows the determination of radiation-induced single-strand breaks without the use of [3H]thymidine prelabeling of cells in culture. The sensitivity of this technique in HeLa cells is comparable to results obtained using the alkaline unwinding technique. The method is applicable to cells in both exponential and plateau phases of growth. PMID- 2928478 TI - [The effect of tularemia vaccine on the radioresistance of white rats exposed to x-irradiation]. AB - A single epicutaneous vaccination of Wistar rats with tularemic live vaccine 15 days before X-irradiation with doses of 6.0, 8.0 and 2.0 + 6.0 Gy was shown to increase their radioresistance. With higher doses (up to 8.0 Gy) the effect of the vaccine was less pronounced. PMID- 2928479 TI - [The immuno-microbiological status of mice after partial exposure to x-rays and the possibility of its correction using immunoglobulin]. AB - Partial X-irradiation of the hind part of mouse body with a dose of 12 Gy (LD15/30) was shown to produce a pronounced harmful effect on the clinico hematologic and immuno-microbiological characteristics that could be coped with by a single subcutaneous injection of homologous immunoglobulin (200 mg/kg) 2 h following irradiation. PMID- 2928480 TI - [Cholinergic processes as affected by small doses of radiation on the host]. AB - Acetylcholine content of blood and cholinesterase activity in blood and tissues of albino rats were studied at different time-intervals after gamma-irradiation with doses of 12.9 and 25.8 mC/kg. Cholinergic processes were found to change with the development of radiation dose. PMID- 2928481 TI - [The possible participation of protein SH groups and aldehydes in radiation damage of cell membranes]. AB - The sedimentation method was used to study the effect of N-ethylmaleimide, diethyl maleate, formaldehyde, Ca2+, and dithiothreitol on cell membranes. Sedimentation quality of erythrocytes was shown to be modified by the agents that bound protein SH-groups and aggregated proteins. PMID- 2928482 TI - [The effect of ionizing radiation on the transmethylation of phospholipids in the high molecular complex acyl-tRNA-synthetase]. AB - Transmethylation was found to contribute to the postirradiation redistribution of phospholipids which enter high molecular weight complexes of rat liver aminoacyl tRNA-synthetases. The kinetic capacity of methyltransferases of codosome phospholipids was studied in normal conditions and at early times after irradiation of rats with a dose of 0.21 C/kg. PMID- 2928483 TI - [Evaluation of the expression of damage of the DNA-structural complex of rat thymocytes based on kinetics of alkaline lysis following irradiation]. AB - Rotary viscosimeters were used to study the postirradiation destruction of the DNA-structural complex (DSC) of rat thymocyte nuclei exhibited by a change in alkaline denaturation of DSC upon lysis. The S area, limited by the characteristic viscosity values obtained during alkaline lysis of thymocyte nuclei, was used as a characteristic of DSC. Immediately after irradiation the S area changed up to 81-84 per cent at 0.5-1.5 Gy and up to 56-44 per cent at 2-10 Gy. 6 to 24 h following irradiation a change in the profile of alkaline denaturation of DSC was a function of dose and dropped from 100 down to 11 per cent at doses of 0 to 10 Gy. After 2-3 days, the changes in S were also observed but they were not a strict function of dose and were the same with the values obtained immediately after irradiation. PMID- 2928484 TI - [Electrophoretic analysis of the internucleosome fragmentation of DNA in irradiated thymocytes of rats]. AB - Total DNA and DNA of chromatin degradation products obtained from rat thymocytes 6 h after irradiation with a dose of 10 Gy were separated electrophoretically. Relative shares of mononucleosomes and their oligomers were determined. Experimental distributions of DNA fragments differ from those calculated on the basis of the assumption of a random breakage of bonds between the nucleosomes. PMID- 2928485 TI - [Changes in lipid metabolism in rats with radiation sickness and a pronounced intestinal syndrome following local irradiation of the abdominal region. Fatty acid composition of the blood and tissue phospholipids]. AB - Local irradiation of rat abdomen (13.5 Gy) caused similar changes in fatty-acid composition of phospholipids in the liver, thymus and brain, that is: (a) a decrease in the polyunsaturated fatty acid content in 4 h, (b) a hypercompensatory increase in the content of polyunsaturated fatty acids (excluding thymus) in 24 h, the ratio between essential fatty acids and their derivatives being changed towards accumulation of the latter, and (c) a trend toward normalization in 72 h. PMID- 2928486 TI - [Acetylcholine in the brain of rats exposed to acute irradiation]. AB - A two-fold increase in acetylcholine, that can randomly be released by brain synaptosomes, is registered 60 min following whole-body X-irradiation of rats with a dose of 0.21 C/kg; depolarization of the synaptosome membranes by potassium chloride increases the release of acetylcholine the augmentation of the release in this case being lower than that in the control. The initial rate of spontaneous neuromediator release from synaptosomes grows by 80 per cent whereas after depolarization of synaptosome membranes by potassium chloride, by 15 per cent. There is a 2.5-fold increase in the maximum rate of a highly specific uptake of choline with Km value being constant. Acetylcholine content of gray substance of irradiated rat brain is invariable. PMID- 2928487 TI - [The content of pyridoxal coenzymes in the brain and liver of rats exposed to a single irradiation with x-rays]. AB - A study was made of the effect of a single exposure of rats to 0.4 Gy X-radiation on the content of pyridoxal phosphate and pyridoxamine phosphate in gray and white brain substances and liver. At the same time changes were noted in the activity of pyridoxal kinase in the tissues under study. PMID- 2928488 TI - [Mechanisms of the development of radiation lesions and processes of recovery of hematopoietic tissue during prolonged gamma-irradiation with a dose of magnitude 0.1 Gr per day]. AB - The following dynamics of the amount of major bone marrow cell populations was observed upon continuous 250-day exposure of rats to gamma-radiation at a dose rate of 0.1 Gy/day: the haemopoiesis was stimulated during the first three months, then the main parameters were stabilized (within the physiological fluctuations). Lymphopenia, neutrophilic leukocytosis and a trend towards the decrease in the erythrocyte level developed in the peripheral blood of exposed rats. PMID- 2928489 TI - [The effect of normobaric hypoxic stimulation on the aggregation properties of blood cells in an irradiated host]. AB - The influence of a short-term intermittent stimulation by hypoxia on the aggregative properties of platelets and erythrocytes of irradiated body has been investigated. The results show a favourable effect of hypoxic stimulation on some platelet aggregation indices. PMID- 2928490 TI - [Activation of the DNA repair system in tissues of mice subjected to chronic gamma irradiation]. AB - Mice exposed to gamma-quanta during 47 and 82 days at a dose-rate of 1.3 mGy/h and cumulative doses of 1.45 and 2.54 Gy, respectively, were subsequently subjected to a single acute irradiation with a dose of 20 Gy. Repair of DNA damages induced by the acute exposure was shown to proceed in the brain, pulmonary and splenic tissues of chronically exposed mice more readily than in the tissues of mice not subjected to chronic irradiation. The data obtained indicate that the induced adaptive response activates DNA repair in tissues of mice exposed to long-term low-level radiation. PMID- 2928493 TI - Hyperthermia. PMID- 2928492 TI - [The effect of modifying factors on the absorption of radioactive beryllium from the gastrointestinal system of rats]. AB - In experiments with rats a study was made of the influence of pregnancy and lactation as well as of trivalent and bivalent iron on the resorption of 7BeCl2 from the digestive tract and distribution thereof among organs and tissues. PMID- 2928491 TI - [Modification of the interphase death of thymocytes: the effect of agents inhibiting the killing process]. AB - The influence of different killing inhibiting agents on the interphase death of irradiated rat thymocytes has been investigated. The results confirm the previously proposed hypothesis of the interphase death mechanism involving activation of killing potency in the irradiated population of thymus cells. PMID- 2928495 TI - Laserthermia. A new method of interstitial local hyperthermia using the contact Nd:YAG laser. AB - Laserthermia is a new method of delivering interstitial local hyperthermia using a synthetic contact probe with a computer-controlled Nd:YAG laser to deliver both pulsed and continuous laser energy. The system allows an easily controllable increase in temperature (for example, from 42 to 43 degrees C) over a fixed period of time (for example, 20 minutes) to be delivered to tissue. A single or multiple channel system can be used depending on the volume of tissue to be treated. Tumor necrosis appears to be related to avascular infarction. Early clinical results support the beneficial therapeutic effects of Laserthermia in its oncologic applications. PMID- 2928494 TI - Clinical experience with thermotron RF-8 capacitive heating for bulky tumors: University of Minnesota experience. AB - We conducted a phase I clinical trial of the feasibility of using the Thermotron RF-8, a capacitative heating device utilizing 8-MHz RF, for the treatment of deep seated and bulky human tumors. Preclinical studies with agar phantoms demonstrated that deep heating can be achieved with this device when the electrode diameters are sufficiently large relative to the thickness of the heated object. In the clinical application of capacitive heating with radiofrequency, excessive heating of subcutaneous tissue has often been a problem. However, this could be minimized by continuous cooling of the subcutaneous fat with a 10 degrees C saline bolus, beginning more than 20 minutes prior to the start of heating. It was often possible to raise the temperature of deep-seated tumors even in obese patients by applying this pre-cooling method. The mean achieved temperature during 30 to 40 minutes of heating was higher than 42 degrees C and 40 degrees C to 42 degrees C in 26% and 50% of 58 tumors treated, respectively. A combination of hyperthermia (four to ten sessions, twice a week) with full-course or a limited dose of radiotherapy resulted in complete tumor remission in 7% of patients, and partial tumor remission in 50% of patients. In the full-course radiotherapy group, 69% of the tumors were judged to show complete or partial regression, and in the low-dose group, 43% of the tumors regressed completely or partially. Histologic examination of many of the tumors that did not regress showed massive necrosis, indicating that tumor size after hyperthermia is not an accurate criterion of the treatment result. Side effects were minimal, and vital sign changes during heating were insignificant. Our data, together with those reported by Japanese investigators, clearly demonstrated that hyperthermia with the Thermotron RF-8 in combination with radiotherapy is useful in treating deep-seated and bulky tumors that fail to respond to conventional treatment modalities. PMID- 2928496 TI - Three-dimensional magnetic resonance imaging of the heart. AB - Three-dimensional surface images of the human heart may be produced from magnetic resonance imaging. These examinations are used in the evaluation of congenital heart disease for preoperative planning and postoperative evaluation. Computer graphics software has been adapted to produce three-dimensional images of the beating heart from contiguous two-dimensional serial EKG-triggered magnetic resonance image data sets. The natural boundary between flowing blood and cardiac tissue serves to outline cardiac structures. The techniques for producing these images and pitfalls in the operation of the system as well as examples of their application to the study of patients with congenital heart disease are outlined in this article. PMID- 2928497 TI - Assessment of the continuing education needs of California's radiologic technologists. AB - The California radiologic community was surveyed concerning Continuing Education (CE) to determine (1) the factors that affect participation, (2) preferred CE activities, and (3) opinions on adding CE to existing certification law. Generally, respondents recognize CE's value for radiologic technologists and its cost effectiveness. Respondents are more likely to attend if financially supported. Though all populations recognize CE's value, radiologists favor enactment of mandatory CE, while technologists prefer state encouragement for CE. PMID- 2928499 TI - A common artifact revisited. PMID- 2928500 TI - Radiation therapy technology shortage and recruitment. PMID- 2928498 TI - The influence of film-screen color sensitivity and type of measurement device on kVp measurements. AB - Three methods for evaluating radiographic kVp were studied: the Wisconsin Test Cassette, the Noninvasive Evaluator of Radiation Outputs (NERO), and the Dynalyzer. The Dynalyzer kVp readings were the highest and were followed by NERO and cassette readings in descending order. By film type, the cassette readings ranged from Kodak OG (green sensitive), TMG (green sensitive), XK (blue sensitive), and XRP (blue sensitive) in descending order. The results show that there is significant variation between the methods. PMID- 2928502 TI - Teaching by lecture. PMID- 2928501 TI - The hospital "exodus" from in-house sponsored education programs. PMID- 2928503 TI - No males in mammography. PMID- 2928504 TI - Males in mammography--a silly suggestion. PMID- 2928506 TI - Limited technologists--another opinion. PMID- 2928505 TI - Expanding the discipline--recognition of the limited technologists. PMID- 2928507 TI - [Possibilities of MR tomography of diseases of the hand and wrist]. AB - MRI studies of 63 patients with various abnormalities of the hand and wrist were analyzed. Studies were performed on scanners with a field strength of 0.35, 0.5, or 1.5 T. Imaging parameters included T1- and T2-weighted sequences in the coronal and transverse planes and contiguous slices 3-5 mm thick. In 37 patients with post-traumatic disorders, MRI revealed carpal avascular necrosis, tendon abnormalities and, in some cases, abnormalities of interosseous ligaments and the triangular fibrocartilage. In 15 patients with such inflammatory diseases as arthritis, tenosynovitis and carpal tunnel syndrome and in 11 patients with tumors, MRI provided clear delineation of osseous and soft tissue abnormalities. The current role of MRI in the diagnosis of hand and wrist abnormalities is discussed on the basis of these results. PMID- 2928508 TI - [Traumatology and diagnosis of scaphoid fracture]. AB - In 9 years, 1,104 patients had one or more roentgenological studies of the scaphoid; 252 fractures of the scaphoid were found. The most reported traumatic mechanism was a fall on the extended wrist. The form of fracture most seen was transverse fracture of the scaphoid; most of the fractures were found in the middle third of the scaphoid. The primary radiodiagnostic procedure should contain pictures of the wrist in two planes and four special pictures of the scaphoid. The "fat-pad sign" seems to be an unreliable indicator of fracture, but nearly two-thirds of fractures of the scaphoid showed a swelling of the soft tissues in the X-ray picture. PMID- 2928509 TI - [CT diagnosis of malalignment following distal radius fracture]. AB - Examination of 29 cases of fracture of the distal radius with restricted motion or persistent pain in 22 patients showed that most had been caused by incongruity of the distal radioulnar joint or by rotational malalignment in supination or pronation. Imaging of the distal radioulnar joint without superimposition enables us to detect whether disorders of the joint facets are impeding movement. Exact knowledge of the malalignment aids in the planning of osteoplastic surgery. PMID- 2928510 TI - [Enthesopathic reactions of the wrist in psoriatic arthritis, chronic polyarthritis and diffuse idiopathic skeletal hyperostosis. Results based on 3 dimensional soft radiographs]. AB - Twenty-six sites of muscle and ligament attachment around the wrist were evaluated for enthesopathic proliferative bone changes in psoriatic arthritis (PA), rheumatoid arthritis (RA), and diffuse idiopathic skeletal hyperostosis (DISH). Proliferations were found to be most frequent, most irregular, and largest in PA, followed in declining order by RA and DISH. In PA only, the bony proliferations and the underlying bone often had the appearance of mineralized woven bone, though smooth proliferations with a regular bone structure do occur in PA as well as in RA. The entheses of the trapezium, scaphoid and the radial styloid process are most frequently affected, followed by the bases of the first and fifth metacarpals and the pisiform. It is exceptional for huge bony proliferations to be observed at the entheses in DISH. PMID- 2928511 TI - [CT diagnosis of cystic hygroma]. AB - We present five patients with cystic hygroma: the CT features are presented. It occurs primarily in the region of the neck. Occasional involvement of the axilla, the chest wall and the mediastinum is possible. PMID- 2928512 TI - [Calcifications. Juvenile dermatomyositis]. PMID- 2928513 TI - Chronic diffuse infiltrative lung disease: comparison of diagnostic accuracy of CT and chest radiography. AB - The accuracies of chest radiography and computed tomography (CT) in the prediction of specific diagnoses in 118 consecutive patients with chronic diffuse infiltrative lung disease (DILD) were compared. The radiographs and CT scans were independently assessed by three observers without knowledge of clinical or pathologic data. The observers listed the three most likely diagnoses in order of probability and recorded the degree of confidence they felt in their first-choice diagnosis on a three-point scale. Confidence level 1 (definite) was reached with 23% of radiographic and 49% of CT scan readings, and the correct diagnosis was made with 77% and 93% of those readings, respectively (P less than .001). The correct first-choice diagnosis regardless of the level of confidence was made with 57% of radiographic and 76% of CT scan readings (P less than .001). The CT scan interpretations were most accurate in silicosis (93%), usual interstitial pneumonia (89%), lymphangitic carcinomatosis (85%), and sarcoidosis (77%). Observers correctly predicted whether a transbronchial or open lung biopsy was indicated with 65% of radiographs and 87% of CT scans (P less than .001). It is recommended that CT be performed before lung biopsy in all patients with chronic DILD. PMID- 2928514 TI - Radiographic type p pneumoconiosis: high-resolution CT. AB - High-resolution computed tomography (CT) was performed in 90 patients with pneumoconiosis who had small rounded opacities on radiographs. The CT appearances of radiographic type p small rounded opacities in 55 patients were compared with the appearances of type q and r opacities. Radiographic type p pneumoconiosis on high-resolution CT scans was characterized by tiny binary branching structures or a gathering of a few dots. In 21 of the 55 patients, nonperipheral, small areas of low attenuation with a central dot were found. On the basis of CT-pathologic correlation in two postmortem specimens, these tiny opacities and areas of low attenuation corresponded to irregular fibrosis around and along the respiratory bronchioles and to focal-dust emphysema, respectively. Focal emphysema was most commonly found in pneumoconiosis with p-type changes and can be identified with high-resolution CT scanning. The addition of high-resolution CT to chest radiography is useful in achieving more accurate categorization of the lesions. PMID- 2928515 TI - Costal pleura: appearances at high-resolution CT. AB - The appearance of the costal pleura at high-resolution computed tomography (CT) was evaluated with a cadaver and 25 normal subjects. This was contrasted with the high-resolution CT appearance of the costal pleura in 15 patients with mild pleural thickening, 13 of whom had been exposed to asbestos. On high-resolution CT scans in the normal subjects, a 1-2-mm-thick line of soft-tissue attenuation at the point of contact between lung and chest wall represents the visceral and parietal pleura, pleural contents, endothoracic fascia, and innermost intercostal muscle. In a paravertebral location, the innermost intercostal muscle is lacking, and a thin line seen on high-resolution CT scans reflects pleura and endothoracic fascia. Transverse thoracic and subcostal muscles and extrapleural fat pads can be seen as tissue internal to a rib and may be confused with pleural thickening. In 13 of the 15 patients with mild pleural thickening, the 1-3-mm-thick pleura was separable from the underlying normal intercostal muscle by a layer of extrapleural fat. High-resolution CT was more sensitive than CT with 1-cm collimation in depicting this degree of pleural abnormality. PMID- 2928516 TI - Left azygos lobe. AB - Left azygos lobe is much rarer than right azygos lobe, but cases have been reported. Computed tomography proved more reliable than plain radiography in the diagnosis of left azygos lobe in a 10-year-old girl. PMID- 2928517 TI - Femoral capital osteonecrosis: MR finding of diffuse marrow abnormalities without focal lesions. AB - Six painful hips in five patients were examined with magnetic resonance (MR) imaging and were found to have diffuse signal abnormalities in the marrow of the femoral head and neck, which extended into the intertrochanteric area in five cases. The abnormal regions were low in signal intensity on images obtained with a short repetition time (TR) and a short echo time (TE) and were isointense or hyperintense on long TR/TE images--findings that have been attributed by others to bone marrow edema. Edema was also seen in marrow just above the acetabulum in two cases. No focal abnormalities characteristic of osteonecrosis were seen. Osteonecrosis was subsequently shown to be present in all six femoral heads at core biopsy (three cases) or by subsequent development of focal MR abnormalities reported to be highly specific for osteonecrosis (three cases). The affected hips had been radiographically normal or subtly osteopenic and had shown intense radionuclide uptake in the femoral head at scintigraphy, with lesser abnormality in the neck and intertrochanteric region. Follow-up MR examinations of five of the six femoral heads showed the diffuse abnormalities to have been transient. Although diffuse MR abnormalities in the proximal femur are not specific, they may indicate the presence of osteonecrosis of the femoral head. PMID- 2928518 TI - Osteomyelitis: diagnosis with In-111-labeled leukocytes. AB - In a retrospective review, 485 patients with suspected osteomyelitis were studied. Of these, 453 patients were studied with both bone and indium-111 leukocyte scanning (173 sequentially and 280 simultaneously). The ability to determine that the infection was in bone rather than in adjacent soft tissue was greater with simultaneous bone scan and In-111 leukocyte studies than with sequential studies. The locations of suspected osteomyelitis were divided into central (containing active bone marrow), peripheral (hands and feet), and middle (between central and peripheral). Specificity remained high (about 90%) regardless of the location. Overall sensitivity was significantly lower in the central location than in the peripheral or middle location. Determination of whether the In-111 leukocyte activity was in bone or adjacent soft tissue was also more difficult when the infection was in the central location. For acute osteomyelitis, sensitivity was high regardless of the location. For chronic osteomyelitis, sensitivity was lower in the central location. PMID- 2928519 TI - Hip pain in three children accompanied by transient abnormal findings on MR images. AB - In a study of three children experiencing hip pain, low-signal-intensity patterns in the femoral head on T1-weighted magnetic resonance (MR) images eventually resolved, reverting to the normal signal patterns. These findings occurred in conjunction with documented clinical improvement of the patients' condition. T2 weighted images revealed isointense signals initially at the abnormal sites. Isointense signals prevailed on follow-up T2-weighted images. These MR imaging findings are likely due to transient bone marrow edema. These findings support the apparent sensitivity of MR imaging in the evaluation of marrow-based pathologic processes. Some pediatric patients with hip pain may have signs of transient bone marrow edema, rather than avascular necrosis, on MR images. Conservative management should be considered in such cases. PMID- 2928520 TI - Cranial bone marrow in children: assessment of normal development with MR imaging. AB - Magnetic resonance images of cranial bone marrow in 238 patients (246 examinations) less than 25 years old were reviewed to establish normal age related standards. Bone marrow in the clivus and calvaria had uniformly low signal intensity (grade 1) on T1-weighted images in most infants less than 1 year old. The number of patients with grade 1 marrow decreased rapidly in early childhood, while the number of patients with marrow of low and high signal intensity (grade 2) and uniformly high signal intensity (grade 3) gradually increased with age. A grade 1 marrow was no longer observed in either the clivus or calvaria after age 7. Most patients had a grade 3 marrow by age 15. Because bone marrow in certain pathologic conditions has decreased signal on T1-weighted images and therefore resembles grade 1 or 2 appearances of normal marrow in children, these results may be useful for differentiating normal and abnormal bone marrow signal intensities in infants and children. PMID- 2928521 TI - Larynx: MR imaging at 2.35 T. AB - To study the consequences of an improvement in spatial resolution, the authors compared magnetic resonance (MR) images of nine laryngeal specimens with whole organ histologic slides of the same specimens. Five of the specimens were obtained during laryngectomies performed on patients with high-stage tumors of the larynx. Four specimens were from patients with no known disease. The MR images were obtained on a 2.35-T system with a closely fitting probe head. A conventional spin-echo sequence was used, with T1- and T2-weighted settings. The in-plane resolution obtained was about 0.3 mm. The T2-weighted images generally showed better contrast and allowed identification of the perichondrium. The resolutions used were not much greater than those clinically available. The findings suggest that there will be important advances in clinical MR imaging of the larynx in the near future. PMID- 2928522 TI - CT diagnosis of blunt hepatic and splenic injuries: a look to the future. PMID- 2928523 TI - Traumatic brain stem injury: MR imaging. AB - Eighty-seven patients with acute (n = 70) or chronic (n = 17) head injuries were prospectively studied with magnetic resonance (MR) imaging and computed tomography (CT) to characterize the frequency and nature of traumatic brain stem injury (BSI). Forty-eight traumatic lesions were identified in 36 patients. Of 36 patients, 35 had neurologic findings that corroborated the radiographic impression of BSI. T1- and T2-weighted MR images demonstrated a significantly higher number of lesions than did CT. Patients with BSI had a significantly higher frequency of corpus callosum and diffuse axonal "shear" lesions. The number of cortical contusions and extraaxial hematomas was similar in both groups. The mean Glasgow Coma Scale (GCS) scores at admission were significantly lower in patients with evidence of BSI on MR images. Patients with primary BSI had lower initial GCS scores, a longer duration of coma, more diffuse axonal "shear" lesions, and a higher frequency of corpus callosum injury than patients with secondary BSI. The location of primary and secondary lesions was significantly different. Overall, MR imaging was more helpful than CT in detecting, localizing, and characterizing BSI. PMID- 2928524 TI - Septo-optic dysplasia: MR imaging. AB - Septo-optic dysplasia is the diagnosis when optic nerve hypoplasia is seen in conjunction with dysgenesis of the septum pellucidum. Nearly two-thirds of these patients have hypothalamic-pituitary dysfunction, and half have schizencephaly. The disorder is difficult to classify because of the diversity of clinical and pathologic manifestations. Magnetic resonance images of 11 patients with clinical and radiographic evidence of septo-optic dysplasia were reviewed retrospectively. The "syndrome" appears to include two subsets of patients whose abnormalities have different embryogenesis and neuropathologic findings. The existence of these two subsets helps to explain the diversity of the clinical and radiologic findings. PMID- 2928525 TI - Facet joint arthrography in lumbar spondylolysis: anatomic basis for spread of contrast medium. AB - Facet arthrograms in patients with lumbar spondylolyses show spread of contrast medium through pars interarticularis defects into the adjacent ipsilateral facet joint space and across the midline into the contralateral joint space. Transverse and sagittal sections of facet joints from 141 postmortem lumbar spines were studied. Five examples of spondylolysis were found. Anatomic studies of the relationship of the joint recesses to the pars interarticularis demonstrated the basis for the patterns of spread of contrast medium observed radiographically in this and previous series. The pars interarticularis forms the only boundary between the inferior recess of one facet joint and the superior recess of the adjacent joint. Fracture through the pars interarticularis establishes communication between adjacent ipsilateral joints and opens a communication to the retrodural space, through which contrast medium can track to the contralateral joint. PMID- 2928526 TI - Normal and disrupted lumbar longitudinal ligaments: correlative MR and anatomic study. AB - The posterior and anterior longitudinal ligaments of the lumbar spine appear on magnetic resonance (MR) images as thin lines of very low signal intensity in all spin-echo sequences. They cover the periphery of the outer fibers of the anulus fibrosus on sagittal images. The lumbar spine of 17 patients with 19 disk herniations was prospectively evaluated with MR imaging, and these findings were correlated with surgical findings. At surgery the posterior ligament was found to be disrupted in eight cases and intact in 11. Absence of a low-signal peripheral line around the herniated nucleus pulposus (HNP) was the most reliable sign of ligament rupture (no false-negative or false-positive findings). The peripheral line appeared to be interrupted in four cases, two of which were falsely positive. The two false-positive cases were related to a chemical shift artifact between epidural fat and the HNP. Presence of a normal and continuous peripheral line outlining the HNP excluded ligament disruption. The overall sensitivity for detecting disruption was 100%, and the specificity was 78%. PMID- 2928527 TI - Tetralogy of Fallot: MR findings. AB - Surgical treatment of patients with tetralogy of Fallot requires accurate definition of all anatomic structures, particularly the central pulmonary arteries. Magnetic resonance (MR) images of 22 patients with tetralogy of Fallot were studied to assess their usefulness in providing information regarding the spectrum of anatomic abnormalities in this condition. MR findings were compared with information obtained at catheterization (in 16 patients) and at surgery (in nine patients), both of which were performed within 3 months of MR imaging. Ventricular chamber enlargement and wall hypertrophy were clearly delineated in most of the 17 patients who were examined before definitive surgical repair, and ventricular septal defects were visualized in all 17. Palliative systemic-to pulmonary shunts were visualized in 11 patients and could be evaluated for patency. Most important, the morphology and size of the right ventricular outflow tract and central pulmonary arteries could be accurately assessed. Pulmonary artery measurements obtained from MR images demonstrated excellent correlation with angiographic measurements. In six patients examined after complete surgical repair, MR images accurately reflected changes in pulmonary artery outflow tract morphology and complications, such as residual pulmonary artery stenosis and thrombosis. The findings suggest that MR imaging can complement or obviate catheterization in the evaluation of tetralogy of Fallot with regard to suitability for definitive surgical repair. PMID- 2928528 TI - Thrombus imaging with an I-123-labeled F(ab')2 fragment of an anti-human fibrin monoclonal antibody in a rabbit model. AB - The murine monoclonal antibody MA-15C5 binds to cross-linked fibrin but not to fibrinogen. Fab or F(ab')2 fragments of MA-15C5, labeled with iodine-123, were injected intravenously into nine rabbits with a nonocclusive 0.2-mL human plasma clot in the jugular vein and into eight control rabbits. Scintigrams obtained at hourly intervals after injection of the F(ab')2 fragment revealed a significantly higher accumulation of tracer in the clot region than in the contralateral region. The relative excess of tracer in the jugular vein region was significantly greater in the study animals than in the control animals throughout the study period. Blind reading of serial scans revealed no visible tracer accumulation in seven of eight control rabbits, whereas the scans of seven of nine study rabbits showed clearly visible accumulation (sensitivity = 77%, specificity = 87%). The Fab fragment of MA-15C5 had a lower affinity and bound less avidly to the blood clot in vivo. These results suggest that the F(ab')2 fragment has better imaging properties than the Fab fragment and that it may be useful for imaging blood clots in man. PMID- 2928529 TI - Mechanical clot dissolution: new concept. AB - The authors present preliminary data on in vitro mechanical clot dissolution by means of a catheter with a tiny high-speed propeller enclosed in a special housing. Preweighed human blood clots were subjected to the catheter in a test tube with saline at various propeller speeds and durations of application. After filtration of the resultant slurry, the clot residue was weighed and examined histologically. Clot dissolution was found to be related to both the duration and speed of propeller rotation. No fibrin residue was seen after dissolution, although potential embolic material, composed of clumps of cellular debris as large as 208 microns in longest dimension, was found. Mechanical clot dissolution could possibly be used in any natural or synthetic blood vessel in which there is acute or subacute thrombosis, with fewer complications and lower cost than obtained with traditional methods. PMID- 2928530 TI - Gallbladder ablation through radiologic intervention: an experimental alternative to cholecystectomy. AB - Twenty pigs underwent (a) cystic duct occlusion by means of fluoroscopically guided transcatheter endoluminal bipolar radio-frequency (RF) electrocoagulation and (b) gallbladder sclerotherapy with one of two different regimens of ethanol and sodium tetradecyl-sulfate (STS). Serum ethanol levels and hepatic enzyme tests showed no acute toxicity. Postmortem histologic studies showed that the bile ducts beyond the occlusion site remained entirely unaffected in all animals. In three of four animals followed up for 2 weeks, the sclerosants induced necrosis of the gallbladder mucosa, but the adjacent liver, serosa, and blood vessels remained intact. In 13 of 16 animals followed up for 8 weeks, the gallbladder lumen was obliterated by fibrous scar tissue. In the animals treated with 95% ethanol and 3% STS, the gallbladder mucosa was necrotic in all areas after 2 weeks (two of two animals) and eradicated completely after 8 weeks (six of eight animals); the other regimen (70% ethanol plus 1% STS) was somewhat less effective. In this study, the combination of RF-mediated cystic duct occlusion and gallbladder sclerotherapy with ethanol and STS permitted gallbladder ablation in swine without toxic side effects. PMID- 2928531 TI - Uterine junctional zone: MR study of water content and relaxation properties. AB - Weighted samples of uterine myometrium, junctional zone, and endometrium were excised for determination of T1 and T2 in a 20-MHz spectrometer and then dried for determination of water content. The remainder of each uterus, examined with special histopathologic stains, demonstrated no significant difference in the number of blood vessels, smooth muscle cells, fibroblasts, elastin, iron, collagen, mucin, polysaccharide, or amyloid. The junctional zone water content (79.28%) was significantly lower than that of endometrium (82.88%, P = .004) and myometrium (81.05%, P = .005). The T1 of the junctional zone (ie, 643) was significantly lower than that of endometrium (ie, 836; P = .004) and myometrium (ie, 709; P = .01). The T2 of the junctional zone (ie, 58) was significantly lower than that of endometrium (ie, 87; P = .003) and myometrium (ie, 67; P = .006). The low signal intensity of the junctional zone on T2-weighted MR images is accounted for by its lower water content and T2, while the brightness on T1 weighted images is due to its reduced T1. PMID- 2928532 TI - Carcinoma of the cervix: staging with MR imaging. AB - Demonstration and staging of carcinoma of the cervix with magnetic resonance (MR) imaging was evaluated prospectively in 67 patients with histologically proven lesions. Findings were correlated with surgical/pathologic results obtained within 2 weeks. MR imaging had an accuracy of 95% in demonstrating invasive disease (stage IB or higher). It was capable of depicting the location and extent of tumor invasion of cervical stroma and helped detect tumor beneath relatively normal epithelium or within the endocervical canal that had not been detected by means of colposcopic biopsy. The overall accuracy of MR imaging in staging carcinoma of the cervix was 76%, and in demonstrating parametrial status, the overall accuracy was 89%. In 39 patients with proven invasive disease, the accuracy in demonstrating parametrial status was 82%. In 13 of these 39 patients the low-signal-intensity stromal ring of the cervix on MR images was completely preserved and there were no false-positive results. MR imaging is a highly promising method for directly demonstrating and staging carcinoma of the cervix and seems to be capable of providing answers to crucial questions regarding mode of therapy. PMID- 2928533 TI - Using MR imaging to probe the pathophysiology of osteonecrosis. PMID- 2928534 TI - Evaluation of a quadtree-based compression algorithm with digitized urograms. AB - The effect of a quadtree-based data-compression algorithm on the diagnostic yield in digitized radiographs was studied for 100 urograms. Each image was digitized and reviewed at nine decreasing compression ratios ranging from 90:1 to 4.2:1, followed by a review of the uncompressed digital images. Four radiologists independently reviewed the digitized images and the original radiographs and agreed on a reference standard of 201 findings. Sensitivity, measured by the number of findings noted on the compressed digital images, decreased with increasing compression ratios at and above the 11:1 level. No loss of sensitivity was noted with a compression ratio of 4.2:1. Sensitivity decreased more precipitously for calcifications than for soft-tissue masses. Only a minimal loss of sensitivity for bilateral renal function was noted, even with high compression ratios. False-positive rates were unaffected by compression. The authors conclude that quadtree compression ratios of 11:1 and higher may result in loss of sensitivity in clinically relevant findings. PMID- 2928535 TI - Fetal dose estimates for CT pelvimetry. AB - Fetal and maternal dose estimates for computed tomographic pelvimetry have been obtained from phantom measurements. Use of routine abdomen imaging techniques may result in localized fetal doses in excess of 13 mGy (1.3 rad). With the use of a low-exposure (40-mAs) technique, it is possible to obtain images of acceptable quality for the necessary measurements. The resulting dose to the fetus is approximately 2.3 mGy (0.23 rad). PMID- 2928536 TI - Volumetric rendering of MR images. AB - The authors developed new techniques for three-dimensional display of magnetic resonance (MR) images that preserve soft-tissue definition, are fully automatic, and work with routinely used section thicknesses. MR images are segmented, selectively enhanced, and displayed by means of a volumetric rendering algorithm. These techniques were used to illustrate normal anatomy of the brain, knee, and liver. Three-dimensional rendering of balanced spin-echo images shows the ventricles and extracerebral veins and of T1-weighted images, the sulci and gyri. The large hepatic and portal vessels can be seen with these enhancement techniques. Three-dimensional views of the knee reveal articular surfaces of the tibia and clearly depict menisci and posterior and anterior cruciate ligaments. These techniques make it possible to image multiple soft tissues simultaneously while preserving the detail contained in the original images. Three-dimensional presentation of complex, overlapping anatomic regions is helpful in surgical planning and should lead to improved diagnosis. PMID- 2928537 TI - Blunt hepatic trauma in adults: CT-based classification and correlation with prognosis and treatment. AB - To further define the computed tomographic (CT) criteria on which to guide the nonsurgical treatment of adult patients with blunt hepatic injury, the authors retrospectively reviewed abdominal CT scans obtained before surgery during a 35 month period. Blunt hepatic injury was diagnosed in 187 patients, and review revealed 37 patients in whom the liver was the site of sole or principal intraabdominal injury detected with the help of CT before surgery. A CT-based hepatic injury classification system partly derived from similar systems established with surgical assessment was devised to grade the severity of hepatic injury. CT-based injury scores ranging from grade 1 to 5 were compared with the clinical outcome in patients treated surgically and nonsurgically. Thirty-one patients (83.7%) were successfully treated without surgery, and four patients (10.8%) had findings at celiotomy that did not require further surgery. No patient who was initially treated without surgery required delayed celiotomy due to hepatic injury. The results indicate that even major hepatic injury up to and including grade 4 severity assessed with preoperative CT can usually be managed without surgery in hemodynamically stable patients. PMID- 2928538 TI - T1 and T2 measurements on a 1.5-T commercial MR imager. AB - In order for relaxation times to be used in clinical diagnosis, the precision of the measurement must be determined. The authors measured T1, T2, and proton density in a phantom and in human volunteers to determine the reproducibility of the method. The coefficient of variance of T1 measurements in the phantom during a 15-month period with two software upgrades was 5%. Variance of T2 measurements with any given software was 4% or less, and overall in the 15-month period, with two software changes, the T2 reproducibility was between 6% and 9%. The reproducibility is sufficiently high that precise clinical measurements of T1, T2, and proton density are feasible. PMID- 2928539 TI - Surface of the brain: three-dimensional MR images created with volume rendering. AB - Image processing and volume rendering have been applied to magnetic resonance (MR) images to produce three-dimensional views of the surface of the brain. Four healthy volunteers and 17 patients with a variety of disorders underwent MR imaging of the head, and these images were processed and subjected to volume rendering. The resulting three-dimensional views depict abnormalities of the brain surface, as well as important landmarks of normal brain surface anatomy such as precentral, postcentral, superior temporal, and inferior frontal gyri, which are difficult to identify on cross-sectional images. PMID- 2928540 TI - National Institutes of Health and academic radiology: a view from the inside. PMID- 2928541 TI - The routine upper gastrointestinal examination. PMID- 2928542 TI - Esophageal strictures: balloon dilation. PMID- 2928543 TI - Radiologist site visitors sought. PMID- 2928544 TI - Blunt splenic trauma in adults: CT-based classification and correlation with prognosis and treatment. AB - Nonsurgical management of blunt splenic injury in children is a well-established method to salvage splenic function; however, nonsurgical management of adult blunt splenic trauma remains controversial. To assess the value of preoperative abdominal CT in predicting the outcome of blunt splenic injury in adults, a CT based injury-severity score consisting of four grades was devised and applied in 39 adult patients with blunt splenic injury as the sole or predominant intraperitoneal injury detected with preoperative CT. While patients with high grades of splenic injury generally required early surgery, eight (35%) of 23 patients with initial grade 3 or 4 injury were treated successfully without surgery, and four (29%) of 15 patients with grade 1 or 2 injury initially treated nonsurgically required delayed celiotomy (n = 3) or emergency rehospitalization. Results show that while CT remains an accurate method of identifying and quantifying initial splenic injury, as well as documenting progression or healing of critical injury, CT cannot reliably help predict the outcome of blunt splenic injury in adults. Treatment choices should therefore be based on the hemodynamic status of the patient and results of serial laboratory and bedside assessments. PMID- 2928545 TI - Gastrointestinal tract: dynamic MR studies with echo-planar imaging. AB - Gastrointestinal (GI) tract motility was depicted in four human volunteers with the high-speed echo-planar imaging technique: modulus blipped echo-planar single pulse technique (MBEST). Data acquisition times of 64 and 128 msec obviate image degradation due to motion without the need for gut paralysis and allow imaging of the GI tract in real time. Peristaltic patterns of the gastric antrum and proximal small intestine were depicted for fasting and fed subjects and subjects in whom peristalsis had been pharmacologically stimulated. The potential for quantitative measurements of GI tract motion with this new technique was demonstrated. PMID- 2928546 TI - Cystic neoplasms of the pancreas: comparison of MR imaging with CT. AB - Cystic neoplasms of the pancreas are divided into two major groups: microcystic adenomas and mucinous cystic neoplasms. Five microcystic adenomas and seven mucinous cystic neoplasms (three cystadenomas and four cystadenocarcinomas) were examined with both magnetic resonance (MR) imaging and computed tomography (CT). The cystic content was differentiated more easily with MR imaging than with CT. It was homogeneous in four of the five microcystic adenomas, all of which had lobulated borders best seen on T2-weighted images. The mucinous cystadenomas and cystadenocarcinomas were all composed of multiple compartments that varied in signal intensity. The septa, shape, and wall thickness were demonstrated on T1- and/or T2-weighted MR images almost as well as on CT scans. Overall, MR imaging was equal or slightly superior to CT in the diagnosis of pancreatic cystic neoplasms, except in its limited ability to demonstrate calcifications of the tumor wall and septa. PMID- 2928547 TI - Interobserver variation in the interpretation of abdominal radiographs. AB - A total of 140 sets of abdominal radiographs were reviewed independently by four qualified diagnostic radiologists. The degree of interobserver agreement was determined by calculating kappa values for 19 commonly used radiographic signs and diagnoses. There was fair to excellent interobserver agreement for 11 signs and diagnoses and poor agreement for the remaining eight. The signs and diagnoses for which agreement is poor cannot be considered reliable and include particularly large bowel obstruction and nonspecific gas pattern. PMID- 2928548 TI - The biliary lithotripsy team: the necessity for an interdisciplinary approach. PMID- 2928549 TI - Liposomal Gd-DTPA: preparation and characterization of relaxivity. AB - Gadolinium diethylenetriaminepentaacetic acid (DTPA) has not proved particularly useful for hepatosplenic magnetic resonance imaging. However, by entrapping the Gd-DTPA within lipid vesicles, one may exploit the ability of the reticuloendothelial system to endocytose particulates, permitting passive delivery of contrast agent to the liver and spleen while decreasing the rate of clearance of Gd-DTPA from the vasculature. Liposomes of 70-400 nm diameter containing Gd-DTPA were prepared by a freeze-thaw extrusion process. These exhibited high trapping efficiencies and excellent stability during storage. For all sizes of liposomes, the relaxivity of the entrapped Gd-DTPA was less than that of free Gd-DTPA. Relaxivity varied linearly with the surface-area-to-volume ratio of the liposomes; the smaller the liposomes, the greater the relaxivity. Liposomes containing cholesterol had a lower relaxivity than liposomes without cholesterol. The authors suggest this reflects the decrease in the water permeability coefficient caused by the presence of cholesterol in the liposome membrane. PMID- 2928551 TI - Mammography registry: considerations and options. AB - Radiologists are being urged to provide high-quality low-cost screening mammography to all women over 40 years of age. A mammography registry coupled with existing cancer registries would permit the quality and effectiveness of screening efforts to be evaluated. Standards of care would be determined that would permit quality assessment at individual centers and that could enhance medicolegal defense. The organizing group should consist of physician users, experts in mammography, statisticians, and administrators. Data regarding the number and type of studies, findings, interpretations, and recommendations could be collected and reported easily and cheaply with a standardized form. The registry could be financed by federal, state, or private funds; the latter are most preferable, but a combination of the three is most feasible. Screening mammography presents a serious public health challenge that is best addressed by the organization and support of a registry by radiologists. PMID- 2928550 TI - Hepatic metastases: liposomal Gd-DTPA-enhanced MR imaging. AB - Liposomal gadolinium diethylenetriaminepentaacetic acid (DTPA) encapsulated within 70- and 400-nm vesicles was tested as a contrast agent for magnetic resonance (MR) imaging of the liver in rats with hepatic metastases. Liposomal Gd DTPA caused significant improvement in contrast between liver and tumor (P less than .005) on T1-weighted MR images. Smaller 70-nm liposomal Gd-DTPA vesicles caused greater contrast enhancement, reflecting the larger surface-area-to-volume ratio of the smaller vesicles. Liposomal Gd-DTPA-enhanced images permitted significant improvement in metastasis detection by five blinded radiologists (P less than .005). By comparison, free Gd-DTPA without liposomes caused a statistically significant reduction in contrast between tumor and liver and reduced lesion detection (P less than .01). Liposomal Gd-DTPA also resulted in sustained vascular enhancement for 1 hour after administration. The results suggest that paramagnetic liposomes may become a useful MR imaging contrast agent. PMID- 2928552 TI - Newborn trauma mystery: Res Ipsa Loquitur. PMID- 2928553 TI - Failure to use triage slips: death in E.R. Case in point: Montoya v. John Peter Smith Hosp. (760 S.W. 2d 361--TX (1988)). PMID- 2928554 TI - Legal case briefs for nurses. NE.: sexual assault: Respondeat Superior issue; N.Y.: physician's failure to communicate: orders. PMID- 2928555 TI - Penrose drain left in patient: continuing tort. Case in point: Jumper v. Healthone Corp. (699 F. Supp. 220--SD (1988)). PMID- 2928556 TI - Radiation dose assessments in radioiodine (131I) therapy. 1. The necessity for in vivo quantitation and dosimetry in the treatment of carcinoma of the thyroid. AB - In order to destroy thyroid cancer metastases by radioiodine an average tissue dose of 80-300 Gy is needed. Such high doses can be expected, following the administration of the conventional 5.5 GBq of 131I, only if both the percentage uptake per gram in the target tissue and the effective half life of the radioiodine in it are higher than well-defined threshold values, and if every dimension of the tissue exceeds several millimeters. The fulfillment of such favourable conditions in actual clinical cases can only be confirmed by in vivo quantitation of the absorbed dose achieved as a result of the administration of radioiodine. PMID- 2928557 TI - Radiation-induced lung damage: dose-time-fractionation considerations. AB - The comparison of different dose-time-fractionation schedules requires the use of an isoeffect formula. In recent years, the NSD isoeffect formula has been heavily criticized. In this report, we consider an isoeffect formula which is specifically developed for radiation-induced lung damage. The formula is based on the linear-quadratic model and includes a factor for overall treatment time. The proposed procedures allow for the simultaneous derivation of an alpha/beta ratio and a gamma/beta time factor. From animal data in the literature, the derived alpha/beta and gamma/beta ratios for acute lung damage are 5.0 +/- 1.0 Gy and 2.7 +/- 1.4 Gy2/day respectively, while for late damage the suggested values are 2.0 Gy and 0.0 Gy2/day. Data from two clinical studies, one prospective and the other retrospective, were also analysed and corresponding alpha/beta and gamma/beta ratios were determined. For the prospective clinical study, with a limited range of doses per fraction, the resultant alpha/beta and gamma/beta ratios were 0.9 +/ 2.6 Gy and 2.6 +/- 2.5 Gy2/day. The combination of the retrospective and prospective data yielded alpha/beta and gamma/beta ratios of 3.3 +/- 1.5 Gy and 2.4 +/- 1.5 Gy2/day, respectively. One potential advantage of this isoeffect formalism is that it might possibly be applied to both acute and late lung damage. The results of this formulation for acute lung damage indicate that time dependent effects such as slow repair or proliferation might be more important in determining isoeffect doses than previously predicted by the estimated single dose (ED) formula. Although we present this as an alternative approach, we would caution against its clinical use until its applicability has been confirmed by additional clinical data. PMID- 2928558 TI - Complications of uterine cervix carcinoma treatments: the problem of a uniform classification. AB - Ninety-six articles published in English, French and Italian between 1938 and 1986 have been examined in order to analyze the classifications and reporting methods used by different researchers. Specialty and nationality of authors, classifications used, organs, systems and anatomic sites considered, weight given to the most frequently encountered complications are studied. Fifty-nine papers make no use of classification of complications of any kind, neither by onset time, nor by severity, but simply describe the observed events. The remaining 37 papers use a classification based on varying criteria. Thirty-four authors use a classification by severity according to different criteria; four authors classify complications according to the treatment required. In the remaining 30 papers a true scale is used. A total of 22 classifications emerges from these papers; in eight cases a previously published classification is used. The weight assigned by different authors to specific complications has been compared. The following main points emerge from the analysis: about two authors out of three simply describe the observed complications; 30 rely on a true scale of severity, but 22 different grading systems are used. Most classifications do not cover all possible complications, both surgical and radiotherapeutic, but concentrate on those complications which are typically generated by author's therapeutic approach. Only three take into account complications related to different treatment modalities. The observation period is not standardized: published data derive from follow-up times spanning from some months to many years. Authors mainly focus their interest on gastrointestinal and/or urinary complications; other organs and systems are rarely considered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2928559 TI - [Treatment of subdiaphragmatic lymph node metastases of primary testicular seminoma (stage II)]. AB - From January 1968 through December 1985, 123 patients with subdiaphragmatic lymph node metastases from testicular seminoma were observed. Eighty-five patients presented with metastases not bigger than 5 cm (stage II low), and they were all treated with radiotherapy (target dose: 35-45 Gy). Out of 38 patients with advanced retroperitoneal disease (because of metastases bigger than 5 cm: stage II, bulky), 18 were treated with radiotherapy, 14 with chemotherapy, and 6 with combined radiotherapy and chemotherapy; moreover, 14 out of 38 patients underwent surgical treatment (whole/partial lymph node resection). Actuarial relapse-free survival rate has proven higher for "low" patients than for "bulky" ones, both at 5 years (85.4% versus 75.8%) and at 10 years (83.5% versus 75.8%). On the contrary, overall survival has been higher for "low" patients at short-term follow-up only (90.4% vs 83.9% at 5 years), while long-term follow-up (10 years) has proven the same in both groups. Relapses (22 cases) occurred within 2 years in 75% of cases, and within 3 years in 90%. Overall incidence of lymph node recurrence has been 10.6%, higher in "bulky" patients (13.3% if treated with radiotherapy alone and 21.4% if treated with chemotherapy and/or surgery). Distant metastases occurred in 8.1% of cases. Long-term salvage treatment by chemotherapy was performed on 1/13 failures in stage II "low" patients and in 3/9 failures in stage II "bulky" patients. Four patients underwent effective salvage therapy in the "low" group, 3 by radiotherapy and 1 by surgery. The authors stress how curative radiotherapy appears to be the best treatment for retroperitoneal lymph node metastases less than 5 cm diameter, while chemotherapy is still to be demonstrated to yield better results than radiotherapy as first treatment for patients with advanced abdominal disease. PMID- 2928560 TI - [Double pseudoaneurysm of the left ventricle. The diagnostic value of computed tomography]. PMID- 2928562 TI - [Peutz-Jeghers syndrome: a case description]. PMID- 2928561 TI - [Kommerell diverticulum. Current aspects of the imaging diagnosis]. PMID- 2928563 TI - [A journal..."nonviable, lacking editorials, commentaries, presentations on topical themes..., lacking a robust column of letters to the editor"]. PMID- 2928564 TI - [Digital radiography in urography]. AB - The clinical utility was evaluated of a computed radiographic system in urography. The system (FCR 101, Philips Medical Systems, Inc., Shelton, CT) is based on a photo-stimulatable phosphor screen (imaging plate) for X-ray image detection and storage. The X-ray information recorded on the imaging plate is converted into digital from and processed by means of a computer. After processing is completed, the digitized image is reversed back to analogic signals, which modulate the intensity of a laser beam scanning the image on a single-emulsion film (Fuji CR 633). Two hundred IVP's were obtained in four groups, of 50 patients each, with normal azotemic values by rapid infusion of a low osmolality contrast medium (iopamidol 150 mgI/ml). While conventional radiographs were performed on the first group of patients with the injection of 0.6 gI/kg body weight of contrast medium, digital examinations were carried out, in the remaining three groups, with the injection of 0.6, 0.3 and 0.12 gI/kg, respectively. The digital images were processed with the "Abdomen-routine" program. A specific algorithm was implemented in order to reduce the excessive contrast resolution of the bladder, which is due to the characteristics of the nonionic contrast medium and enhanced by the reading program. The image details were evaluated by two observers and then statistically analyzed with nonparametric tests. Statistical analysis did not show any difference in the quality of digital and screen-film images. Image processing improved some inadequate images, by reducing the contrast resolution of the bladder, and allowed a better detection of some details. Low doses (0.3 gI/kg) of a low osmolality (150 mgI/kg) contrast medium were enough to obtain good images. Another biological advantage was obtained by a consistent radiation dose reduction (about 40%). PMID- 2928565 TI - [CT and MR compared in the study of hypophysis]. AB - Normal CT and MR anatomy was studied in two series (53 and 25 cases respectively) of young volunteers of both sexes, asymptomatic and certainly without lesions of the pituitary gland. 115 other pathological cases (73 hyperprolactinemias, 8 acromegalies, 15 Cushing syndromes, 2 hyperthyroidisms, 17 nonsecreting adenomas) were examined using both CT and MRI. Both an accurate review of the relative literature and the results of our own series prove that MR is superior to CT in diagnosing pituitary microadenomas (3.2% not diagnosed with MRI and 25.8% not diagnosed with CT), in the follow-up of prolactinomas subjected to medical therapy and in the study of extrasellar involvement of pituitary adenomas, particularly with regard to the demonstration of compression of the optic chiasma. PMID- 2928567 TI - [Value and limits of CT in the preoperative assessment of primary malignant tumors of bone. Observations in 138 cases]. AB - To estimate the capabilities and limitations of CT in the preoperative evaluation of malignant primary bone neoplasms, 138 patients were examined with high resolution CT and subsequently underwent surgery. In all cases a pathologic examination of the surgical specimen was performed, whose results were compared to CT findings. CT appears to yield important diagnostic contribution to preoperative staging. As a matter of fact, CT shows the tumor extension and its relationship to the adjacent anatomical structures, particularly, it shows the involvement of the muscular and vascular bundles, and that of the articular cavity and medullary canal. These data are of primary importance for planning therapy. The commonest CT limitations are: overestimation of the tumor extension, false positives and false negatives when searching "skip" metastases, and, sometimes, inaccurate definition of the relationship between tumor and vascular bundles and/or articular cavities. These limitations may be overcome by using, when necessary, other techniques--i.e. angiography, bone scan and, above all, MR imaging. PMID- 2928566 TI - [Intracranial hemorrhage studied with a high-field (1.5T) NMR apparatus]. AB - Fifty-two patients were studied with high-field magnetic resonance imaging (1.5T), with T1- and T2-weighted spin-echo pulse sequences. The study was aimed at assessing the efficacy of MR imaging in the evaluation of intracranial hematomas. Characteristic intensity patterns were observed in the evolution of the hematomas, due to the physicochemical changes in hemoglobin. No acute hematomas were observed. In 35 sub-acute hematomas, peripheral hyperintensity could be observed on T1- and T2-weighted pulse sequences. This hyperintensity eventually fills in the hematoma in the chronic stage. In 17 chronic hematomas, a peripheral hypointense ring due to hemosiderin deposits was seen on T1- and T2 weighted scans. The authors conclude that high-field MR imaging is a very sensible diagnostic method in the evaluation of sub-acute and chronic hematomas. PMID- 2928568 TI - [Soft-tissue sarcomas of the extremities. Their assessment with magnetic resonance]. AB - MR imaging was performed on 38 patients with suspected malignant soft-tissue tumors of the extremities. MR diagnostic accuracy was compared with that of other methods. All patients underwent surgical control. In 7 cases MR imaging was employed to demonstrate the tumor response to antiblastic local perfusion. Lesion identification, extension, compartmental evaluation, bone and vascular involvement were the diagnostic parameters considered. In all cases MR imaging detected the lesion, correctly showing the intracompartmental (16 patients) or extracompartmental (22 patients) extension. In 2 out of 6 cases MR imaging did not demonstrate bone invasion, and in 1 case vascular involvement could not be assessed. MR diagnostic accuracy was superior to that of other techniques. Nonetheless, a diagnostic protocol was proposed for the local staging of malignant soft-tissue tumors of the extremities where some diagnostic limitations of MR imaging are taken into account--i.e., inconsistent evaluation of bone and vascular involvement. Plain X-rays and US are the imaging modalities of choice, whereas MR imaging is to be a second-choice diagnostic technique before biopsy. Thus, MR imaging replaces CT, while angiography is to be used in selected cases, where MR imaging is not diagnostic due to vascular involvement. PMID- 2928569 TI - [Bronchopulmonary carcinoma. Anatomico-radiologic correlations of growth dynamics]. PMID- 2928570 TI - [Induction of liver metastases in the rat. An experimental model for research on magnetic resonance]. AB - The authors report their experience in the implantation of hepatic metastases in rat, for research in magnetic resonance (MR) imaging. Tumor cells were directly injected with a fine needle into an hepatic lobe, after enzymatic disaggregation of the cell suspension. Cryopreservation of the cell line is possible after the above-mentioned preparation. Tumor implants were observed in all the 20 animals studied, with size varying from 0.5 to 2.7 cm, according to the time elapsed between inoculation and sacrifice of the rat. On MR imaging the tumors presented the same signal intensity as the corresponding human pathology, on both T1- and T2-weighted sequences. The animal model can be used for the evaluation of the efficacy of MR imaging of the liver, and mainly for the assessment of new organo specific contrast agents. PMID- 2928571 TI - [Pre- and postoperative radiotherapy of oral carcinoma of a locally advanced stage. An analysis of the results and complications]. AB - The combination of radiotherapy and surgery in the treatment of advanced oral carcinoma (T3 and T4 lesions) yields good possibilities of recovery; whether radiotherapy should be given before or after surgery is still debated. Fifty patients with advanced oral carcinomas were analyzed: 24 of them were irradiated before and 26 after surgery; doses ranged from 40 to 56 Gy for the first group of patients, and from 50 to 68 Gy for the second one. The disease-free survival 48 months after the diagnosis was 36% in patients who received preoperative irradiation, and 53.6% in patients who received postoperative radiotherapy; the latter allowed local control of the disease to be significantly improved (chi 2 3.99, 0.01 less than p less than 0.05). The quality of survival was worse in the group receiving preoperative irradiation, because of radiation-induced surgical complications, which were especially observed in patients with diffuse disease. Our findings suggest that postoperative radiotherapy may be advisable if the tumor is resectable, since tolerance and local control rate were acceptable. On the contrary, nearly inoperable masses and massive neck diseases often require preoperative irradiation. PMID- 2928572 TI - Advanced imaging of the wrist. AB - In an effort to improve the radiologist's contribution to the evaluation of the painful wrist, the authors have studied the usefulness of a variety of imaging techniques. Preliminary results of these studies, including: 173 conventional CT, 80 3-D CT, 119 postarthrography CT, 138 multiple compartment digital subtraction arthrography and 55 MRI examinations, are reported, and technical aspects of the examinations are described. PMID- 2928573 TI - Clinical experience with rapid acquisition cardiovascular CT imaging (cine CT) in the adult patient. AB - In this overview of cine-CT technology and its clinical application, the authors discuss the unique features of the imaging unit and describe the scanning programs and projections available for cardiac studies. Application of the unit to physiologic studies (e.g., cardiac output and ejection fractions) are illustrated, and examples of the value of the unit for the diagnosis of septal defects, aortic dissection, valvular regurgitation, prosthetic value malfunction and coronary artery bypass graft occlusion are presented. PMID- 2928574 TI - Improved detection of healed myocardial infarction by Fourier amplitude and phase imaging in two projections: validation with MRI. AB - Biplane Fourier amplitude and phase images from radionuclide ventriculograms were analyzed for the presence of regional wall motion abnormalities in 25 patients who had a total of 33 healed myocardial infarctions (nonviable scar tissue) documented by contrast ventriculography and ECG. This indirect evidence was validated by MRI, which permits direct visualization of healed myocardial infarction. The use of amplitude and phase images in both projections resulted in the detection of more healed myocardial infarctions (91%) than did the use of conventional radionuclide ventriculography with left anterior oblique images alone (67%), because inferior wall infarcts are more readily visualized in the left posterior oblique projection. PMID- 2928575 TI - General case of the day. Massive pulmonary microtumor embolism. PMID- 2928576 TI - Pediatric case of the day. Complete ureteral triplication. PMID- 2928577 TI - Teaching moderately mentally retarded children basic reading skills. AB - The present study assessed the efficacy of a program for teaching moderately mentally retarded children basic reading skills. Central to the program were the use of a phonemic alphabet as well as the application of pictorial cueing and stimulus manipulation techniques. The program consisted of six phases. It started with the training of graphemes for vowels (Phase 1) and ended with the training of two-syllable words (Phase 6). Four moderately mentally retarded students participated. Given time constraints, not all subjects completed all phases of the program. The training ended with the reading of one-syllable three letter words for one subject, one-syllable four letter words for two subjects, and two syllable words for one subject. Subsequent generalization tests revealed that all subjects were capable of reading untrained words of the same complexity as those previously trained; and to read and, to a lesser extent, understand simple sentences. The execution of the program required an average training time of 35 hours per subject. Aspects pertaining to the validity of the program, the efficacy of the procedures, and the relevance of the learned skills are discussed. PMID- 2928578 TI - Nutritional status of institutionalized children and adolescents with developmental disabilities. AB - The relationship was explored between anomalies associated with developmental disabilities and nutritional status of institutionalized children and adolescents who received comprehensive interdisciplinary services. Variables included dietary intake, serum laboratory values, anthropometric measurements, feeding skills assessment, and clinical assessment. Mean intakes of nutrients were greater than 67% of Recommended Daily Allowances. Laboratory values were within normal ranges with the exceptions of serum ferritin, which was borderline or below normal in 46% of the males and 55% of the females, and alkaline phosphatase, which was elevated in 70% of residents receiving anticonvulsants. Energy intake was highest in residents with adequate feeding skills, followed by nonfeeders and feeders requiring behavior management. Subjects had greater triceps skinfold and lower mid-arm muscle circumference and weight measurements as compared to reference data. Findings of this study suggest that these developmentally disabled children and adolescents who received comprehensive interdisciplinary nutritional services, in general, are adequately nourished and have nutrient intakes that meet the RDA requirements. PMID- 2928579 TI - Psychotropic drug use in older developmentally disabled with behavioral difficulties. AB - Use of psychotropic medications with elders who are mentally retarded is a very common procedure. However, patterns of medication usage in this group are not easily determined. Objectives were to explore relationships between prescribed psychotropic treatments, the types of reported behavioral difficulties, and the size/type of living settings where these difficulties were exhibited. Subjects were moderately mentally retarded elders who were living in Congregate and Group care settings who were observed and rated by caretakers using a standard behavior rating instrument. Comprehensive medical (drug) and demographic data was obtained on each person. The study revealed that psychotropic use was more frequent in congregate care settings for these older clients. Those more elderly demonstrated a tendency toward higher utilization. Little differences were evident in the general characteristics (sex, IQ, reality orientation) of elders living in the two settings despite differences in drug use rates. Future research needs to focus on differences in behavior problems and setting factors to more fully understand drug utilization rates in elders with mental retardation. PMID- 2928580 TI - Role relations between children who are mentally retarded and their older siblings: observations in three in-home contexts. AB - Older nonhandicapped siblings and same-sex younger mentally retarded siblings (n = 16 sibling pairs) were observed in their homes during toy play, snack, and television-viewing, as were an equal number of comparison sibling pairs, matched for age, gender, and family characteristics. Role relationships between mentally retarded children and older siblings were asymmetrical, with older siblings assuming frequent teacher, manager, and helper roles. Older sisters, in particular, participated in frequent teaching. Amount of interaction between siblings was directly related to the contexts in which they were observed. Nonhandicapped siblings engaged each other more as playmates. Interactional correlates of language and adaptive competencies of the mentally retarded children are presented, as are correlations between the age of the siblings and the roles they assume with each other. PMID- 2928581 TI - Prevalence of psychopathology among mentally retarded adults. AB - The prevalence of psychopathological disorders was determined in a random, stratified sample of 165 adults, 110 males and 55 females, with mental retardation using the Psychopathology Instrument for Mentally Retarded Adults. Stratified variables included mental retardation level and living environment (institutional, family, independent). Results showed that 35.9% of the sample had at least one significant psychopathological disorder. Presence of pathology was related to level of retardation, but not to living environment, sex, or age. Difficulties associated with assessing pathology in persons with mental retardation are described. PMID- 2928582 TI - [Tuberculosis in 1989]. PMID- 2928583 TI - [Evaluation of the sequelae of occupational asthma]. AB - Current knowledge of the evolution of occupational asthma is based on few clinical studies in groups of patients sensitized to red cedar, colophony, crab boiling water and organic isocyanates. Whatever the sensitizing agent, respiratory sequelae appear to be very frequent (50% or more of subjects removed from exposure) and characterized by the persistence of an asthmatic condition with a variable degree of severity. For the greater part of these cases certain features at the time of diagnosis assessment appear to be of prognostic value for evolution: age, duration of occupational exposure, duration of symptomatic exposure, presence of spirometric alterations, degree of bronchial hyperreactivity. In all cases persistence of exposure after diagnosis produced unchanged or worsened symptomatology as a consequence. After removal from exposure the manner of evolution may be classified in three groups (1. recovery, 2. intermittent attacks lasting more than one month after exposure exclusion, 3. persistence of an airflow obstruction); particularities of their distinctive course are to consider when evaluating sequelae: symptomatology, degree of bronchial hyperreactivity, presence of airway obstruction, need for long-term steroid therapy, impossibility to find another employment on account of asthmatic attacks due to effort in coldness or to atmospheric pollutants, finally the course of intermittent attacks which does not allow a full appreciation of the severity of sequelae before six months or even one year of allergen exclusion. PMID- 2928584 TI - [Chronic cough in adolescents and respiratory symptoms in adults]. AB - The object of this work was to study the relationship between chronic cough in adolescence, and chronic symptoms and airflow obstruction in adults. The data were collected between 1982 and 1984 from 1807 men and women living in Bordeaux (France) and its surrounds. A self administered questionnaire was used which focused on current respiratory symptoms and respiratory symptoms during adolescence. Spirometric curves (FVC, FEV1 and FEF 25-75) were measured. The population was evenly split between men (mean age 40.1) and women (mean age 38.6). Most subjects were French; more than half were non smokers; all socioprofessional categories were represented except farmers, craftsmen and merchants. The proportion of subjects with current respiratory symptoms was 2 to 10 times higher amongst subjects with respiratory symptoms during their adolescence than in those who had none. The relationships were highly significant and remained so after adjustments for the confounding factors following: sex, age, nationality, socio-economic status, smoking habits, occupational exposure and previous occupational disease. Mean spirometric values were higher amongst subjects without chronic cough during their adolescence than those who had cough. Differences were significant for FVC, FEV1, FEF 25-75 in women and were on the borderline for FEF 25-75 in men. This study showed that respiratory conditions in adolescence represent an important risk factor for chronic symptoms and airflow obstruction in adult life. PMID- 2928585 TI - [The frequency of Kaposi's bronchial sarcoma in AIDS. Personal experience in 1987]. AB - In 1987 we carried out 87 broncho-alveolar lavages in 58 HIV positive patients: of these 17 suffered from AIDS and Kaposi sarcoma. Amongst the latter we noticed signs suggestive of bronchial Kaposi sarcoma on five occasions: this is a frequency of 29.5% for the AIDS + Kaposi sarcoma group and of 8.6% for the group overall. PMID- 2928586 TI - [The contribution of computerized tomography to the diagnosis of diffuse pulmonary lymphangiomyomatosis. Apropos of a case]. AB - The authors report a case of lymphangiomatosis (LAM) proven histologically in a 49 year old female. This case benefitted from very detailed CT-scanning (IDM) with characteristic images obtained from the thorax and bilateral renal tumours suggestive of angiomyolipomas. This association seems to be quasi-pathognomic of the disease. The discovery at CT-scanning of cerebral calcification raises a possible connection of LAM with Bourneville's tuberous sclerosis. This CT scanning study has several points of interest: the early diagnosis of pulmonary lesions which are under evaluated by standard radiography; a complete inventory of the possible localisations of the disease; it enables a possible diagnosis in very frail patients in whom a lung biopsy would be a risk; an ability to assess further progress as there also exists a good correlation between the extent of the disease assessed by TDM and the disturbance in pulmonary function. PMID- 2928587 TI - [Multiple bilateral pulmonary nodules and masses]. PMID- 2928588 TI - [Response to the "Open letter to pneumologists"]. PMID- 2928589 TI - [Where are we with the treatment of bronchial cancer?]. PMID- 2928590 TI - Rehabilitation nursing: why not now? PMID- 2928591 TI - Developing and computerizing a patient classification system in a rehabilitation nursing setting. AB - This article describes the process of developing and computerizing a patient classification tool for rehabilitation nursing. When the nursing department of Sharp Memorial Hospital Rehabilitation Center in San Diego, CA, and the nursing division of the entire hospital decided to develop a new acuity instrument, a decision was made to design a tool that would be specific for every unit but would comply with certain parameters to allow for computerizing the system. Computerization of the instrument resulted in a decrease in staff nurses' time spent rating patients, improved accuracy of ratings, ease of auditing, improved management reports, and a decrease in clerical time. PMID- 2928592 TI - The use of therapeutic touch with rehabilitation clients. AB - Therapeutic touch is a holistic nursing strategy that can be incorporated as an adjunctive therapy in rehabilitation nursing practice. Therapeutic touch is a derivative of "laying on of hands" that is based on doctoral nursing research and involves the intentionally therapeutic interaction of energy between the nurse and client. Research has demonstrated its effectiveness in eliciting the relaxation response. In this article, specific case studies are used to illustrate when therapeutic touch may be used, how it is implemented as an adjunctive therapy in a nursing process framework, and how it is documented in the nursing care plan. PMID- 2928594 TI - The development of theory-based practice by graduate students in rehabilitation nursing. PMID- 2928593 TI - A patient self-assessment tool for cardiac rehabilitation. AB - A patient self-assessment tool was designed, tested, and implemented to promote cardiac-specific data collection, based on Gordon's Functional Health Patterns, to maximize patient/family involvement in determining a plan of care, and to streamline primary nurses' documentation requirements. Retrospective and concurrent chart reviews provided data for quality assurance monitoring. The results of the monitoring demonstrated that the self-assessment tool markedly improved the patient-specific data base. PMID- 2928595 TI - [The Diamed Test System (Konig & Partner System House, 1984)--a review]. PMID- 2928596 TI - [Vocational aptitude and inclination--aspects of their assessment and evaluation in rehabilitation]. AB - The task of appraising aptitudes and inclinations accompanies a rehabilitee and the rehabilitation workers involved for the entire duration of an occupationally focussed rehabilitation measure. Explicitly so in vocational guidance measures, it aims at obtaining a sound basis for decision-making in view of vocational reorientation. Responsibility for this decision in the last analysis rests with the rehabilitee himself, an aspect that abolishes any strict separation of aptitude and inclination in predicting outcome in the context of occupational perspectives. Being the decision-making agent, the rehabilitee must therefore be offered typical situational fragments of a possible educational and vocational future, intended on the one hand to inform him of occupational alternatives and, on the other, to provide initial experience. The rehabilitation worker's role in this process requires a client-centered stance in terms of information provider and trusted agent, which is to help avoid an adverse exams climate evolve in this momentous decision-making phase. Psychological testing, from this angle, should be used merely as a supplementary means. The approach outlined for appraisal of individual potentials requires intensive teamwork, not least also in view of verifying individual capacity. PMID- 2928597 TI - [Legal principles for participation of medical service in vocational guidance and education]. AB - Dealt with is the medical profession's legal status in the vocational education and vocational retraining centres. The legal basis for the medical doctor's activities in this type of facilities is clarified, drawing on the legislational history of various rehabilitation-related laws. PMID- 2928598 TI - Insulin-like growth factor I during growth in bulls. AB - In 10 bulls, changes in blood plasma concentrations of insulin-like growth factor I (IGF1) were studied during rearing and during the ensuing growth period. IGF1 continuously increased from 32 micrograms/l at the age of 15 d to 194 micrograms/l at the age of 307 d together with body weight. However, IGF1 was not related to daily rate of gain, which remained fairly constant during the growth period. An age-dependent increase was also observed for blood levels of insulin, thyroxine and triiodothyronine. The data suggest that insulin and thyroid hormones may be causally related to the age-dependent increase in IGF1 levels. PMID- 2928599 TI - Iodine nutrition in ewes: effects of low to high iodine intake on iodine content of biological fluids in pregnant and lactating ewes. AB - In a first experiment, 2 groups of 46 and 47 multiparous ewes received diets which provided an iodine intake of 0.36 and 0.26 mg/kg dry matter (group C) and, 2.01 and 1.94 mg/kg (group D), respectively, for pregnancy and lactation. In a second experiment, 3 groups of 10 nulliparous ewes received diets which provided an I intake of 0.13 and 0.12 mg/kg dry matter (group A), 0.22 and 0.20 mg/kg dry matter (group B), and 10.77 and 8.88 mg/kg dry matter (group E), respectively, for pregnancy and lactation. Observations and sampling were carried out on the ewes from the first third of pregnancy to the 2nd and the 6th week of lactation. The diets provided adequate nutrition for pregnant and lactating ewes. Dietary I content had no effect on the dry matter intake, the size or the weight of the litter and the length of pregnancy. Plasma inorganic iodine (PII) was less affected by the I intake during lactation than during pregnancy. The excretion of I in milk induced a decrease in PII between pregnancy and lactation. The I in urine expressed as microgram I/g creatinine was largely affected by the intake. Colostrum I was 6.7, 4.0, 1.2, 1.3 and 1.5 times higher in groups A, B, C, D and E than the I in milk collected 1 week postpartum. Milk iodine (MI) content and the ratio MI/PII were markedly dependent on the I intake. During pregnancy, plasma T4 concentration decreased for each group. Plasma T4 concentration remained low during lactation in the low I intake group, whereas it increased at the same time in the other groups. The plasma T3 concentration decreased at the 6th week of lactation in the highest I intake group. Experimental values showed that 0.12 mg I/kg dry matter induced depletion in the I stocks of pregnant and lactating ewes, whereas an I intake above 10 mg I/mg dry matter disturbed the metabolism of thyroid hormones. PMID- 2928600 TI - [Marker transfer between food particles during digestive transit in the rabbit. Estimation method based on fecal granulometry]. AB - Five adult rabbits (New Zealand White x Californian) were fed ad libitum for 10 days a pelleted feed compound containing dehydrated lucerne whose particles (0.05 0.5 mm in size) were marked with a rare earth, i.e. ytterbium (Yb). In order to estimate the proportion of marker liable to leave its initial site of binding, we measured the amount of ytterbium present on faeces particles larger than 0.5 mm. The total amount of faeces was collected during the following 3 days. The faeces screening technique used in this study was adapted from that applied to feed. However, the repeatability was low for the large particles (greater than 1 mm), whose number was small. Half of the digesta particles (52%) exhibited a smaller size than 0.05 mm. The proportion of large particles (greater than 1 mm) in the faeces was low (1.5%) while that of the other particle classes ranged from 20 33.5%. After pelleting, more than 40% Yb initially bound to lucerne particles measuring 0.5 to 0.05 mm, was present on fine particles (less than 0.05 mm). Accordingly, only minima and maxima amounts of Yb having migrated on large particles (greater than 0.5 mm) could be measured, i.e. 2.5 and 8.9%, respectively of the ingested Yb. Taking also into account a migration towards small particles, about 10% Yb was liable to leave its initial site during its passage through the digestive tract of the rabbit. PMID- 2928601 TI - Effect of calcium and magnesium ions on the intestinal absorption of oleic acid in vitro. AB - The effect of Ca++ and Mg++ upon intestinal absorption of oleic acid was investigated using two in vitro models: rat isolated jejunal loops at 30 degrees C and 37 degrees C and mouse jejunal explants at 37 degrees C. At 30 degrees C or at 37 degrees C, Ca++ significantly increased 14C oleic acid uptake by rat isolated jejunal loops or mouse jejunal explants; at 37 degrees C, Ca++ significantly enhanced lipid exocytosis in rat intestinal loops but not in mouse jejunal explants; in both models, in the presence of Ca++ and at 37 degrees C, Mg++ significantly improved the esterification of oleic acid phospholipids and triacylglycerols, as shown by the increase in triacyglycerol synthesis in rat isolated intestinal loops or by the increase in triacylglycerols recovered from the incubation media of mouse jejunal explants; experiments carried out with rat isolated jejunal loops highlighted the determinant role of temperature in oleic acid absorption processes. The present work shows that the simultaneous presence of Ca++ and Mg++ did not impede oleic acid absorption processes but, on the contrary, enhanced them. PMID- 2928602 TI - Plasma lactose after weaning and its relationship with lactose content of milk, post-weaning plasma oestradiol-17 beta and weaning to mating interval in sows. AB - Twenty first-liter sows were used to investigate the relationship between plasma lactose concentrations following weaning and milk production, total milk content of lactose, post-weaning plasma oestradiol-17beta (E2) concentration and weaning to mating interval. Milk production was estimated from 6 out of 8 hourly successive "weighing-suckling-weighing" of piglets on day 21 of a 28-day lactation. Sows were cannulated in the jugular vein and sampled at 8-h intervals from 2 h to 66 h after weaning. Plasma lactose concentrations (means +/- SE) after weaning increased from 52 +/- 4 microM at the beginning of sampling to a peak value of 183 +/- 23 microM 40 h later and then decreased to 91 +/- 11 microM 66 h after weaning (P less than 0.001). Milk production on day 21 (7.5 +/- 0.3 kg) and the corresponding milk content of lactose (400.5 +/- 0.2 g) were not related (P greater than 0.10) to area under the curve, timing, amplitude and spreading of the lactose peak in plasma. Similarly, none of the characteristics of the lactose peak were related (P greater than 0.10) to weaning to mating interval. There was a linear increase (P less than 0.0001) in mean plasma E2 concentrations (means +/- SE) from 5.6 +/- 0.3 pg/ml, 2 h after weaning, to 12.9 +/- 1.2 pg/ml at the end of the sampling period. On a within-sow basis, there was a correlation (r = 0.28; P less than 0.01) between post-weaning plasma lactose and E2 concentrations. Results showed the existence of the post-weaning peak of plasma lactose in sows.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2928603 TI - In vivo 13C NMR studies of glucose catabolism by isolated rumen bacteria. AB - Nuclear magnetic resonance (NMR) was used to study the metabolism of the rumen bacterial ecosystem. The fermentation of 1-13C-glucose was investigated. This system showed a transient build-up and decay of lactate labelled at the C3 position. The degradation of lactate gave rise to volatile fatty acids. These results agree with in vivo data on diets rich in available carbohydrates. PMID- 2928604 TI - 17 beta-estradiol secretion in normal and hypophysectomized chick embryos. AB - Ovaries from decapitated, sham-operated and intact 18-day-old chick embryos were cultured in Medium 199 for 6 h, and the amount of 17 beta-estradiol released into the culture media was determined by radioimmunoassay. Ovaries from decapitated embryos secreted significantly lower amounts of 17 beta-estradiol than those from intact embryos, but there was no difference when they were compared to ovaries from sham-operated embryos in this respect. On an ovarian weight basis, 17 beta oestradiol production was significantly different between the 3 groups of embryos, the ratio being highest in the decapitates. 17 beta-Estradiol concentration was the same in serum from both decapitated and intact female embryos. Considering these results, it is concluded that the hypophysis does not control 17 beta-estradiol secretion by the chick embryo ovary even near hatching time. PMID- 2928605 TI - Recombinant human erythropoietin therapy. Part I: clinical issues. PMID- 2928606 TI - [Diagnostic studies in carbon monoxide poisoning]. AB - Origin, symptomatology, seriousness and mechanism of carbon monoxide toxicity have been reviewed as are the diagnosis based on clinical or analytical data upon which the physician may rely to search out a CO intoxication. Treatments are discussed and the best therapy is proposed in case of mild or severe poisonings. PMID- 2928607 TI - [Peroperative radiotherapy]. AB - Tolerance of normal tissues limits the radiation dose which can be safely delivered to tumors especially for gastro-intestinal cancers. Intraoperative radiotherapy is a specialized technique for treating infradiaphragmatic and deeply located tumors allowing to deliver a high dose to the tumor while avoiding surrounding normal tissues which can be moved aside. The authors describe the technique and review indications and possibilities. PMID- 2928608 TI - [Screening in asthma]. AB - One of the most important characteristics of asthma is its association with non specific bronchial hyperresponsiveness. This is diagnosed by histamine bronchial challenge tests. This latter is an easy procedure but requires a precise and standardized methodology. We have analysed, in a large group of bronchial challenge tests (n = 162) the clinical correlations with bronchial response to histamine. Our conclusions are in agreement with several recent literature, and may be summarised as follows: 1. more than 10% of patients, clinically considered as asthmatics do not show bronchial hyperresponsiveness and probably will not benefit from bronchodilators; 2. several aspecific respiratory symptoms (cough, chest tightness, blocked nose and sneezing, recurrent bronchitis, etc...) are frequently associated with bronchial hyperresponsiveness and should be considered as asthmatic manifestations. To conclude, we recommend to realise a histamine non specific challenge test in all cases of clinical suspicion of asthma (with normal lung function at basal state) and in all subjects presenting chest symptoms of uncertain etiology. PMID- 2928609 TI - [Value of examining the placenta in pregnancies complicated by fetal malformations]. AB - This investigation was undertaken to determine whether examination of the placenta contributed to a better understanding of the causes of fetal malformations. Specific histological abnormalities were found in triploidy and lysosomal storage disorders. Placentas from trisomies only showed a marked a specific retardation of villous maturation. The most frequent placental abnormalities detailed in cases presenting major fetal malformations with normal karyotype were: velamentous insertion of the umbilical cord, placental hypotrophy, single umbilical artery, marginal retroplacental hematoma and generalized perivillous fibrin deposition. Examination of the placenta after fetal malformation can provide helpful informations in counseling the parents and the perinatal team in the follow-up of any future child bearing. PMID- 2928610 TI - [A case of fever with eosinophilia and symptoms of muscular necrosis]. PMID- 2928611 TI - [In-vitro fertilization at the University of Liege. Evaluation 1985-1988]. PMID- 2928612 TI - [Health policy aspects: role of the government in the prevention of tobacco abuse]. AB - Possible instruments for control of tobacco-abuse available in a liberal and democratic country are discussed. Prohibition-strategies including bans on advertisement and non smoking areas, reduction of insurance benefits and modifications of liability rules are valued with reservation. Emphasis is placed on fiscal measures and on support of preventive measures exerted by family physicians. PMID- 2928613 TI - [A case from practice (129). Patient: Mr. A.W., born 8-23-1933, electrician]. PMID- 2928614 TI - [Clinical aspects of obstructive pneumopathy (COPD)]. AB - This paper gives a short overview of the most pertinent clinical features and diagnostic measures in chronic obstructive lung disease. In particular, the patient's smoking habits should be questioned extensively, a prolonged expiratory phase identified and pulmonary function tests performed properly. PMID- 2928615 TI - [A case from practice (130). Patient: P.T., born 1959, food engineer (HIV infection CDC Group IV C2 and IV D)]. PMID- 2928616 TI - [Radiological diagnosis of bronchus carcinoma]. AB - Chest radiography is the basic imaging method in lung cancer. It allows early detection of peripheral and, with lower sensitivity, detection of central neoplasms. The subsequent staging procedure includes other imaging tools, first of all computed tomography (CT) for a noninvasive estimate of the local and regional extent. Because of high sensitivity and lower specificity for mediastinal disease, positive CT scans suggesting inoperability ask for cytological verification whereas negative studies justify surgery unless other contraindications exist. During and after treatment, chest radiography again affords a morphological follow up. Systematic comparison of the current with recent and early post-treatment studies is a prerequisite for detecting tiny signs of recurrent disease and for differentiating them from iatrogenic changes and infection. PMID- 2928617 TI - [Magnetic resonance in the assessment of cardiovascular diseases]. PMID- 2928618 TI - [Psychopathology and psychodynamics of self destruction]. AB - Starting from the first publications on the topic as e.g. the famous monograph "Le suicide" written by Durkheim in 1897, the suicide research was based mainly on psychosocial dimensions. Therefore, the main area of research were patients who had survived an attempt of suicide. This led to the faulty conclusion that these patients represent the largest risk group. Today we know that depressive patients represent the number one risk group. They are followed by drug and alcohol addicts, by elderly and lonesome people, by the group of patients who threaten with suicide or who announce it, and finally as a last risk group, by those people who have failed at a first attempt. The psychodynamics show that suicidal behavior is akin to self-aggression. Mainly among younger people occur suicides, which have predominantly the function to appeal, to draw attention to the subject who has been unable to verbalize his problems. One attempt to help these people consists of becoming aware that the wish to die generally goes along with the wish to stay alive, from which result the cries for help and announcements of suicide. Apart from this psychosocial suicide research, in recent years a biological component turned out to be possibly more relevant than originally assumed. With respect to the heredity of suicidal behavior up to now only those suicidal acts were considered that occur within the frame of endogenous depressions. Recent studies however point at an accumulation within families that is not in context with the manic-depressive illness. Biochemical studies indicate in addition that suicidal behavior tends to go along frequently with a lack of serotonin. From this follows that inthe future suicide and suicide treatment will see a biopsychosocial theory as a basis. PMID- 2928619 TI - [A report on experiences using Goldberg's GHQ (General Health Questionnaire)]. AB - The General Health Questionnaire (Goldberg and Hiller, 1978, 1979) is a screening instrument for clinical and preclinical assessment of psychosomatic disorders and proneness to such disturbance. It has been translated into German by F. Gutzwiller for a national health survey (SNF 8/SOMIPOPS) and has been used thereafter in several studies in combination with other psychometric instruments. This current paper presents a set of test-related theoretical and statistical parameters of the GHQ (28-item version). The specificity of the proposed scales (somatic symptoms, anxiety and insomnia, social dysfunction, severe depression) is relatively low in the German version. Nevertheless may the questionnaire be recommended for nonclinical and nonpsychiatric in-patient use, as it picks up aspects of depression and suicidal behavior, of a general disturbance feeling, and of mental and psychophysical stress and exhaustion. Further evaluation is recommended. PMID- 2928620 TI - [Physical examination preceding entry into apprenticeship: preventive measure or administrative burden?]. AB - The new Swiss federal legislation on vocational and trade training requires that all cantons organize a system of medical screening for young people entering an apprenticeship. This paper focuses on the principles and implementation of such an examination. It outlines the most frequent health problems young people may face upon leaving school and entering apprenticeship. It underlines the difficulties of this kind of examination, since absolute contra-indications to distinct professions are very rare. Indeed, the medical examination should not be a selection procedure but much more an occasion to facilitate the transition from school to workplace. With this objective, the canton of Vaud health authority has created an examination sheet that will be supplied each year to the physicians (private pediatricians, general practitioners and internists) examining about 5000 candidates. This instrument introduces a uniform history taking procedure oriented towards occupational medicine and focuses on a few important screening items. No laboratory tests are mandatory. The process does not use a contra indication list, which most of the time appears fallacious. It insists on the importance of an assessment of each individual situation. PMID- 2928621 TI - [A case from practice (132). Mr. D. W., born 1961, electrical fitter]. PMID- 2928622 TI - Sleep deprivation in the rat: III. Total sleep deprivation. AB - Ten rats were subjected to total sleep deprivation (TSD) by the disk apparatus. All TSD rats died or were sacrificed when death seemed imminent within 11-32 days. No anatomical cause of death was identified. All TSD rats showed a debilitated appearance, lesions on their tails and paws, and weight loss in spite of increased food intake. Their yoked control (TSC) rats remained healthy. Since dehydration was ruled out and several measures indicated accelerated use rather than failure to absorb nutrients, the food-weight changes in TSD rats were attributed to increased energy expenditure (EE). The measurement of EE, based upon caloric value of food, weight, and wastes, indicated that all TSD rats increased EE, with mean levels reaching more than twice baseline values. PMID- 2928623 TI - Sleep deprivation in the rat: IV. Paradoxical sleep deprivation. AB - Twelve rats were subjected to paradoxical sleep deprivation (PSD) by the disk apparatus. All PSD rats died or were sacrificed when death seemed imminent within 16-54 days. No anatomical cause of death was identified. All PSD rats showed a debilitated appearance, lesions on their tails and paws, and weight loss in spite of increased food intake. Their yoked control (PSC) rats remained healthy. Since dehydration was ruled out and several measures indicated normal or accelerated use of nutrients, the food-weight changes in PSD rats were attributed to increased energy expenditure (EE). The measurement of EE, based upon caloric value of food, weight, and wastes, indicated that all PSD rats increased EE, with mean levels reaching more than twice baseline values. All of these changes had been observed in rats deprived totally of sleep; the major difference was that they developed more slowly in PSD rats. PMID- 2928624 TI - Sleep deprivation in the rat: VI. Skin changes. AB - All rats subjected to total or paradoxical sleep deprivation by the disk apparatus developed severe ulcerative and hyperkeratotic skin lesions localized to the plantar surfaces of their paws and to their tails. Yoked control rats only occasionally developed similar appearing lesions, which were always much less severe than in deprived rats. The deprived rat lesions could not be explained by pressure, disk rotation, water immersion, infection, necrotizing vasculitis, tyrosinemia, protein deficiency, or reduced rates of mitosis. Thus, although paw and tail lesions constitute a very reliable and severe symptom of total or selective sleep deprivation in the rat that potentially could yield insights into the pathogenic mechanisms induced by sleep loss, the mediation of the lesions remains unknown. PMID- 2928625 TI - Sleep deprivation in the rat: II. Methodology. AB - Methods common to several studies in this series are described. A key feature is a sleep deprivation apparatus in which an experimental and a yoked control rat are housed on opposite sides of a divided disk suspended over shallow water. When the experimental rat enters a "forbidden" sleep stage, the disk is automatically rotated, forcing the experimental rat to walk to avoid being carried into the water. The control rat receives the same physical stimulation but can sleep ad lib when the disk is stationary. PMID- 2928626 TI - Sleep deprivation in the rat: VIII. High EEG amplitude sleep deprivation. AB - The disk apparatus was used to deprive six rats of the portion of non-rapid eye movement (NREM) sleep with high electroencephalogram (EEG) amplitude (HS2). All HS2 deprived (HS2D) rats died or were sacrificed when death seemed imminent within 23 to 66 days. No anatomical cause of death was identified. All deprived rats showed a debilitated appearance, lesions on their tails and paws, and weight loss in spite of increased food intake. Energy expenditure (calculated from the caloric value of food, weight change, and wastes) increased to more than twice baseline values. With one exception, yoked control rats remained generally healthy. It was not clear whether the changes in HS2D rats resulted from the loss of HS2 or the general disruption of NREM sleep that accompanied this loss. Also, it was not possible to produce major HS2 loss without incurring some loss of paradoxical sleep (PS). Control studies indicated that the partial PS loss in HS2D rats could not, in and of itself, account for all the pathological effects. However, an interaction of HS2D and partial PS loss in producing pathological effects cannot be ruled out. PMID- 2928627 TI - International Symposium on Toxic Shock Syndrome. Atlanta, Georgia, 15-18 November 1987. Proceedings. PMID- 2928628 TI - Identification of a new toxin from a strain of Staphylococcus aureus isolated from a patient with nonmenstrual toxic shock syndrome. AB - The extracellular products of a toxic shock syndrome toxin 1 (TSST-1)-negative isolate of Staphylococcus aureus (strain D4508) from a patient with nonmenstrual toxic shock syndrome were shown to possess toxic activity capable of producing shock and death when injected into rabbits. Fractionation of the extracellular products and the production of polyclonal antibodies to individual polypeptides identified the toxin as a single polypeptide of molecular weight 26,000. Immunoblot analyses showed the toxin to be antigenically related yet distinct from enterotoxins A, B, C, D, and E and unrelated to TSST-1. PMID- 2928629 TI - Structure-function analysis of toxic shock syndrome toxin 1. PMID- 2928630 TI - Effect of trace metals on the synthesis of toxic shock syndrome toxin 1. AB - The effect of 10 trace metals on the production of toxic shock syndrome toxin 1 (TSST-1) was studied in a metal-deficient chemically defined medium (CDM) with toxic shock syndrome (TSS) and non-TSS strains of Staphylococcus aureus. When individual metals were tested, only Mg++ stimulated cell growth and TSST-1 production. TSST-1 yield was responsive to the concentration of Mg++ in the medium, with a maximal yield occurring at 0.1 mM. When other metals were studied in the presence of Mg++ with and without 1 mM ethylenediamine tetraacetic acid, it was found that Ca++, Co++, Cu++, Fe++, Mn++, molybdate-, Ni++, vanadate-, and Zn++ produced some stimulation of either cell growth or TSST-1 synthesis or both. The stimulating effect of Mg++ on TSST-1 synthesis was significantly enhanced by adding 0.3 mM Zn++ and 0.003 mM Fe++. TSST-1 production by 11 strains of S. aureus in CDM with optimal concentrations of trace metals was two to seven times greater than that produced in brain-heart infusion broth. PMID- 2928631 TI - Production of toxic shock syndrome toxin 1 by Staphylococcus aureus under aerobic and anaerobic conditions and the effect of magnesium ion limitation. AB - A toxic shock syndrome isolate of Staphylococcus aureus was grown in a chemostat in a defined synthetic medium of six amino acids, glucose, two vitamins, and salts. Steady states were achieved under limiting and replete magnesium ion conditions as well as with and without oxygen. The biomass and the amounts of toxic shock syndrome toxin 1, acid phosphatase, proteinase, hyaluronate lyase, and total exoprotein were estimated at each condition. Under magnesium limitation all variables, measured as specific production rates, were reduced--apart from proteinase--compared with the magnesium-replete condition. A similar pattern of results occurred with comparison of anaerobically and aerobically grown cells. PMID- 2928632 TI - Effect of magnesium on in vitro production of toxic shock syndrome toxin 1. AB - Batch and chemostat culture of Staphylococcus aureus strain S411 was conducted in an investigation of the role of Mg++ in the control of production of toxic shock syndrome toxin 1 (TSST-1). Under both growth conditions, Mg++ influenced bacterial growth, and TSST-1 production was correlated with bacterial growth. The specific activity of TSST-1 (ng/mg yield, ng/mg total protein) increased with increasing concentrations of Mg++ and was maximal at physiologic levels of Mg++. No production of TSST-1 was observed under anaerobic conditions. In chemostat cultures in which valine nutrient limitation was used with various levels of tryptophan in the chemically defined medium, tryptophan concentration controlled the production of TSST-1 by strain S411, regardless of the concentration of Mg++. PMID- 2928633 TI - Magnesium and the pathogenesis of toxic shock syndrome. AB - Excess production of toxic shock syndrome toxin 1 by appropriate strains of Staphylococcus aureus occurs when the organisms are grown in an environment deficient in Mg++. Since many of the fibers previously used in tampons combine with Mg++, an explanation for the pathogenesis of menstrually related toxic shock syndrome presents itself. Pitfalls in the reproduction of these experiments have been investigated and include attention to inoculum size, to the effect of washing the inoculum to rid it of magnesium from the parent culture, and related variables. The growth of staphylococci in magnesium-deficient medium is slower than in the usual culture media, making it necessary that the effect of magnesium deficiency be examined after sufficient incubation to permit maximal toxin production to occur. When these variables are taken into account, a coherent theory to explain the pathogenesis of menstrual TSS emerges. Absorbency of tampons, which correlates with the capacity to absorb Mg++, becomes, as has been suggested, a surrogate for the magnesium effect. The observations raise the possibility of a safer tampon, one in which the magnesium content is regulated to cause the staphylococci not to be in a magnesium-deficient environment. PMID- 2928634 TI - Role of air in growth and production of toxic shock syndrome toxin 1 by Staphylococcus aureus in experimental cotton and rayon tampons. AB - Rayon and cotton fibers of the type used in the manufacture of tampons were extracted for 6 hours in isopropyl alcohol in a soxhlet apparatus to remove all finishes from the fiber surface. The fibers were used to produce experimental tampons of commercial design. Using a syringe method, the tampons were saturated with diluted staphylococci in brain-heart infusion medium and incubated at 37 degrees C. Spent medium was expressed from the tampons and analyzed for growth of staphylococci and production of toxic shock syndrome toxin 1 (TSST-1). Results revealed no statistical difference in the production of TSST-1 by cells grown in rayon or cotton. However, a significant increase in TSST-1 production was observed in tampon cultures when compared with medium controls. When similar experiments were performed with tampons saturated with nitrogen, a significant decrease in TSST-1 production was observed when compared with air-saturated tampons. The results indicate that the oxygen normally present in tampons plays a significant role in modulating the production of TSST-1. PMID- 2928636 TI - Growth of Staphylococcus aureus and synthesis of toxic shock syndrome toxin 1 in different in vitro systems. AB - Various complex and synthetic bacterial growth media have been used to study the growth of Staphylococcus aureus and the production of toxic shock syndrome toxin 1 (TSST-1) under certain in vitro culture conditions. Because of the biochemical and nutritional differences between these media and human menses, a program was designed to determine the growth and metabolism of S. aureus under conditions that more closely approximate in vivo conditions. Human menses, an artificial menses developed to match human menses, whole human blood, and complex bacterial culture media (with and without added whole human blood) were tested for the ability to support the growth of S. aureus and the production of TSST-1 in vitro. In addition, the impact of other organisms, commonly isolated from the human vagina, on the growth of S. aureus and the production of TSST-1 was evaluated. Results show that the environmental conditions provided by human menses are more closely approximated by the artificial menses and that neither commercial bacterial growth media alone nor complex media plus 25% or 50% human blood provide a menses-like environment for the growth of S. aureus and the production of TSST-1. Furthermore, the addition of a second organism to the S. aureus culture resulted in significant suppression of TSST-1 production, even when in vitro conditions were optimized for the production of TSST-1. PMID- 2928635 TI - Ecology of toxic shock syndrome: amplification of toxic shock syndrome toxin 1 by materials of medical interest. AB - Historically, the literature suggests that staphylococcal exoproteins, including enterotoxins, are stimulated by various physicochemical ecologic factors, many of which have been shown to stimulate production of toxic shock syndrome toxin 1 (TSST-1). The propensity of different fibers and other substances to amplify TSST 1 production in toxic shock syndrome-associated strains of Staphylococcus aureus, as well as a comparative analysis of the underlying mechanisms of TSST-1 production, are reported. Two hundred twenty intravaginal devices or other products and materials and 60 experimental controls were examined for their propensity to induce TSST-1 production. Certain materials are superior to unaltered cotton in providing a more absorbent fiber--nutrients are efficiently drawn in, concentrating protein between fibers, and thereby creating an ideal physicochemical environment for the amplification of TSST-1 and other toxins. The greatest stimulation of TSST-1 was observed with (in decreasing order): polyester and carboxymethyl cellulose, polyacrylates, viscose rayon, gelatin foam, polyurethane, and cotton. No toxin was found with nasal tampons (polymer of polyvinyl acetal) or with vaginal cups (an elastomeric polymer). Results are discussed in terms of specific ecologic parameters from historical as well as recent perspectives. PMID- 2928637 TI - Effect of tampon wraps on production of toxic shock syndrome toxin 1. AB - The influence of tampon wraps on the production and distribution of toxic shock syndrome toxin 1 (TSST-1) was investigated with use of a disk-membrane-agar method. Filter membranes (45 micron) overlaying agar medium in 50-mm petri dishes were spread-inoculated with a TSST-1-producing strain of Staphylococcus aureus and covered with 0.5 mL of whole citrated rabbit blood. Disks of tampon core materials with and without wraps were placed on the inoculated membranes and incubated at 37 degrees C in 5% CO2 in air. Eight wraps with each of 14 tampon core materials were tested to determine the amount of toxin in the agar layer, a quantity considered an indicator of the relative amounts of toxin available for absorption in vivo. The average level of toxin in the agar layer with any particular wrap compared with that in the agar layer with no wrap was higher with five wraps, lower with two wraps, and essentially the same with one wrap. The lower levels of toxin were obtained with one wrap that had a starch binder and with one that contained the surfactant Standamul 1414-E. Standamul 1414-E has been reported to be an inhibitor of growth of and production of TSST-1 by S. aureus. PMID- 2928638 TI - Passive protection of rabbits infected with toxic shock syndrome-associated strains of Staphylococcus aureus by monoclonal antibody to toxic shock syndrome toxin 1. AB - The effectiveness of passive immunization was assessed in an infection model of toxic shock syndrome (TSS) in which monoclonal antibody to TSS toxin 1 (TSST-1) was administered intravenously to rabbits. Previously implanted infection chambers were inoculated with Staphylococcus aureus strains RN4710 and D4508. The former strain carries the TSST-1 gene on plasmid pRN6201; the latter is a TSST-1 negative clinical isolate obtained from a patient with nonmenstrual TSS. Purified monoclonal antibody, MAb 8-5-7 (IgG), was administered in two doses of approximately 1.25 mg each 24 hours before and 24 hours after infection. MAb 8-5 7 provided complete protection against both the TSS-like syndrome and the mortality that occurred in unprotected rabbits infected with strain RN4710 but did not provide complete protection in rabbits infected with strain D4508; three of the five rabbits either displayed signs of illness or died despite treatment. Western-blot analyses of the extracellular proteins produced by strains RN4710 and D4508 that used MAb 8-5-7 as a probe revealed that only TSST-1 produced by RN4710 reacted with the antibody. Thus, if MAb 8-5-7 partially protected animals against infections with strain D4508, the protection appears to have been nonspecific. PMID- 2928639 TI - Endotoxin is not an essential mediator in toxic shock syndrome. AB - The hypothesis that toxic shock syndrome toxin 1 (TSST-1) exerts its deleterious effects in toxic shock syndrome (TSS) primarily by enhancing the lethality of small amounts of endogenous endotoxin derived from mucosal colonization with gram negative bacteria was assessed by evaluating two means of inactivating endotoxin in rabbit models of TSS. In both of these models, toxins and TSST-1 are allowed to diffuse constantly from a subcutaneous depot. Immunologic inactivation of endotoxin with antiserum to the core lipopolysaccharide did not change the clinical course or mortality among animals infected with live TSS-associated staphylococci or among animals with a subcutaneous depot of TSST-1. Anti-TSST-1 was successful in preventing disease and death in these models. Pharmacologic inactivation of endotoxin by pretreatment or continuous treatment with polymyxin B did not prevent illness or mortality in the toxin depot model. Endotoxin thus appears not to be an essential mediator in TSS, since TSS-like illness develops and progresses despite inactivation of endotoxin in animal model systems that are faithful both physiologically and clinically to TSS in humans. PMID- 2928640 TI - Update through 1985 on the incidence of toxic shock syndrome among members of a prepaid health plan. AB - Through hospital records of men and women aged 15-34 years who were members of the Northern California Kaiser-Permanente Medical Care Program, trends in the incidence of toxic shock syndrome (TSS) requiring hospitalization in 1984-1985 were examined, and the results were compared with those for the period 1972-1983. No definite or probable cases of TSS were found in men during either 1984 or 1985. A total of 16 cases of TSS (10 definite and six probable) were found in women in 1984-1985. Ten (71%) of 14 cases for which the menstrual status of the patient could be determined unambiguously from the medical record occurred during menstruation, and two of the four nonmenstrual cases occurred in postpartum women using barrier contraception. Of the 16 cases, 14 (88%) were diagnosed as TSS or probable TSS by the attending physician, although only nine (64%) of the 14 diagnosed cases were given the correct discharge code. While trends in the incidence of TSS requiring hospitalization in women 15-34 years of age generally paralleled changes in the absorbency of available tampons, the contribution of other factors (e.g., changes in the chemical composition of tampons, changes in patterns of tampon use) to these trends could not be assessed. PMID- 2928641 TI - Response of various animal species to experimental infection with different strains of Staphylococcus aureus. AB - An experimental infection program was conducted in rabbits, pigs, and baboons with toxic shock syndrome (TSS)-associated and non-TSS-associated strains of Staphylococcus aureus to produce an animal model for TSS. TSS-associated strains of S. aureus--whether positive or negative for TSS toxin 1 (TSST-1)--could not be distinguished from non-TSS-associated strains of S. aureus by means of the rabbit whiffle-ball infection model; therefore, limited pilot infection studies were conducted in pigs and baboons. Experimental conditions were optimized in both the pig and the baboon studies to maximize the chance of producing TSS. Pigs infected with TSS-associated S. aureus strain CDC-11 developed some of the clinical signs observed in TSS (fever, hypotension, diarrhea, and vomiting). However, no changes were detected in clinical chemistry or hematology. Baboons infected with S. aureus strain CDC-11 showed only minimal signs of illness, i.e., lethargy, decreased food intake, and loose stools. TSS was not produced in pigs or baboons, even under optimal exposure conditions. PMID- 2928642 TI - Vaginal tampon model for toxic shock syndrome. AB - The effects of tampon composition, inoculum size, and simulated menses on production of toxic shock syndrome toxin 1 (TSST-1) and toxic shock syndrome (TSS) were evaluated in a rabbit model that simulates tampon use in humans. Three small generic compressed-fiber tampons were successively inserted vaginally (remained in place 4.5 hours x 2; overnight x 1). Tampon no. 1 was inoculated with live TSST-1-positive staphylococci plus 5 mL of saline or simulated menses (defibrinated rabbit blood plus 2.5 g of bovine serum albumin/dL) immediately after insertion; saline or simulated menses alone were used with tampons no. 2 and 3. The vagina was washed after removal of tampon no. 3. TSS-like illness was produced consistently in animals with carboxymethyl cellulose/polyester foam tampons, which supported higher organism counts and greater TSST-1 production in association with subsequent tampons. Cotton and rayon tampons were not associated with as much clinical illness, organism growth, or TSST-1 production. Simulated menses supported toxin production and clinical illness when the inoculum was one tenth that required for controls. Sham tampon insertion was associated with TSS like illness in two of 10 rabbits; thus, other factors may promote TSS in the absence of vaginal tampons. This model reliability reproduces menstrual TSS, since one-time vaginal inoculation with TSST-1-positive staphylococci in the presence of blood and certain tampons leads to TSS, and may be useful in evaluating catamenial products and in understanding other factors important in TSST-1 production in vivo and the development of TSS. PMID- 2928643 TI - Toxicity of staphylococcal toxic shock syndrome toxin 1 for germ-free and conventional piglets. AB - The susceptibilities of conventional and germ-free miniature pigs to staphylococcal toxic shock syndrome toxin 1 (TSST-1) were studied and compared. TSST-1 at doses of 100 micrograms/kg evoked reactions similar to those observed in rabbits, i.e., hyperthermia, diarrhea, apathy, conjunctival hyperemia, and various changes indicating toxic damage of different organs, but it was never lethal at this dose. Germ-free piglets were less susceptible than were corresponding conventional animals, a finding that may support the concept that endogenous endotoxin is involved in the pathogenesis of toxic shock syndrome. PMID- 2928644 TI - Production of toxic shock syndrome toxin 1 in a mouse model of Staphylococcus aureus abscess formation. AB - A mouse model of abscess formation is described in which toxic shock syndrome toxin 1 (TSST-1) is produced by Staphylococcus aureus in vivo. Mice injected intravenously with S. aureus developed renal abscesses within 4-7 days. Kidneys excised from infected mice were cultured quantitatively, and extracts from the kidneys were assayed for TSST-1 with use of a competitive enzyme-linked immunosorbent assay. Animals with less than 10(7) S. aureus/g of kidney had less than 6 ng of TSST-1/mL of extract. Toxin levels ranged from less than 6 ng/mL to 271 ng/mL in kidney extracts from mice with greater than 10(7) S. aureus/g of kidney. Urine from infected mice also contained measurable levels of TSST-1 (range, less than 6-728 ng/mL). Mice developed serum antibodies to TSST-1 by 2 weeks after challenge. Serum samples collected 5-7 days after bacterial challenge did not show biochemical changes typical of a toxic shock-like illness in these animals. PMID- 2928645 TI - Damaging effect of toxic shock syndrome toxin 1 on chick embryo cells in vitro. AB - The lethal effect of staphylococcal toxic shock syndrome toxin 1 (TSST-1) on rabbits and chick embryos is enhanced in the presence of lipopolysaccharide (LPS). In an investigation of the mode of action of TSST-1, its effect-both singly and in combination with LPS-on tissue culture cell lines was examined. Of a variety of cell lines examined for sensitivity to TSST-1 treatment, only primary chick embryo cells were susceptible. At a critical concentration (0.2 microgram/mL), TSST-1 alone caused detachment of the cell monolayer. In contrast, LPS per se had no visible effect on the cells at any concentration tested. TSST-1 in combination with LPS caused monolayer detachment at all concentrations of TSST 1 employed; thus detachment was independent of TSST-1 concentration in the presence of LPS. The ability of TSST-1 to disrupt the monolayer was neutralized in the presence of polyclonal rabbit antiserum to TSST-1. In a time course study over 24 hours, the effect of the toxin on the cells was initially visible by light microscopy after 4-7 hours. Clear differences in cellular morphology between TSST-1 treated monolayers and untreated controls were observed by scanning electron microscopy. Treated cells lost their normal spindle-shaped appearance before detachment. PMID- 2928646 TI - Active surveillance for toxic shock syndrome in the United States, 1986. AB - Active surveillance for toxic shock syndrome (TSS) was established in 1986 in Los Angeles County and in the states of Missouri, New Jersey, Oklahoma, Tennessee, and Washington. Case reports were solicited through biweekly contact with all acute-care hospitals. One hundred sixteen definite and 63 probable cases were reported; 85% of the cases occurred in female patients and 15% in male patients. Among cases in females, 83 (55%) were menstrual; the mean age of the patients with menstrual cases was 23 years (range, 12-46 years). The overall incidence of TSS was 0.53/100,000. The cumulative incidence varied significantly by region, ranging from 1.23/100,000 in Oklahoma to 0.22/100,000 in New Jersey (P = .0001); the incidence in all other areas ranged from 0.39/100,000 to 0.70/100,000. The incidence of menstrual TSS was 1.05/100,000 women 15-44 years of age and peaked in women between the ages of 15 and 19 years at 1.52/100,000. The incidence was higher in whites than in nonwhites for both menstrual TSS (1.21/100,000 vs. 0.34/100,000, P = .002) and nonmenstrual TSS (0.30/100,000 vs. 0.14/100,000, P = .031). Our data indicate that TSS continues to be a cause of morbidity. Although there is underreporting in national passive surveillance, the proportion of menstrual cases reported through active surveillance was similar to that reported to the passive system in 1986. PMID- 2928647 TI - Reaction of toxic shock syndrome toxin 1 with endothelium of human umbilical cord vein. AB - The binding of toxic shock syndrome toxin 1 (TSST-1) to the endothelium of human umbilical cord veins and arteries was studied. Radiolabeled TSST-1, perfused through a segment of human umbilical cord vein, bound to the vessel at 4 degrees C, with a dissociation constant (Kd) of 6.5 X 10(-10) M. A pre-embedding electron microscopic immunogold technique revealed that TSST-1 was located in the veins and arteries on the surface of endothelial cells and in the area of cell contacts. Umbilical cord vein segments filled with TSST-1 were incubated for 30 minutes at 37 degrees C, fixed by perfusion and embedded in hydrophilic resin (Lowicryl K4M). Postembedding immunogold staining of ultrathin sections showed TSST-1 in the vesicles crossing the cytoplasm of the veins' endothelial cells and entering underlying elastic and collagen layers. PMID- 2928649 TI - Direct effects of purified staphylococcal toxic shock syndrome toxin 1 on myocardial function of isolated rabbit atria. AB - Toxic shock syndrome is associated with reversible cardiomyopathy. The cardiac dysfunction may be mediated by toxic shock syndrome toxin 1 (TSST-1), an exotoxin generated by Staphylococcus aureus. However, the effects of purified TSST-1 on cardiac function are unknown. In a study of the toxin's effect on myocardial function, TSST-1 (200 ng/mL) was added to muscle baths containing isolated rabbit atria. TSST-1 caused time-dependent inhibition of developed force (systolic function) but did not alter resting force (an index of muscle stiffness or cardiac compliance). These data show that TSST-1 can directly inhibit myocardial function, but the significance of this effect in patients with toxic shock syndrome remains to be determined. PMID- 2928648 TI - Characteristics of toxic shock syndrome toxin 1-induced lectin-like activity and inhibitor(s) in rabbit serum. AB - In adult rabbits intravenously injected with toxic shock syndrome toxin 1 (TSST 1) or staphylococcal enterotoxin B, serum lectin-like activity (detectable by cation-dependent agglutination of bacteria) developed. This activity was sensitive to heat, trypsin, and formaldehyde but resistant to neuraminidase or galactose oxidase. Formaldehyde-fixed Propionibacterium acnes or Escherichia coli cells reactive with plant lectins provided sensitive targets for titration of serum agglutination activity that was competitively blocked with D-galactose, D glucose, D-mannose, and alpha-L-fucose. The lectin-like activity, partially purified by affinity chromatography, was a protein of approximately 76,000 Da with an isoelectric point of 5.4. Both lectin-positive and normal serum contained agglutination inhibitors that were absorbed by protein A-producing staphylococci. S protein may be the origin of this lectin-like activity. In vitro exposure of peripheral-blood mononuclear cells to TSST-1 (1.0 micrograms/mL) and to lectin positive serum induced rapid cell clumping and subsequent "activation" to a larger blast form expressing receptors for buccal epithelial cells. The interaction of toxin/lymphokine-activated mononuclear cells with glycoproteins and/or other antigens selectively expressed by tissues in various organ systems may play a role in target cell pathology in rabbits dying with toxic shock syndrome. PMID- 2928650 TI - Effects of monoclonal antibody on biologic function of toxic shock syndrome toxin 1 in vitro and in vivo. PMID- 2928651 TI - Risk factors for menstrual toxic shock syndrome: results of a multistate case control study. AB - For assessment of current risk factors for developing toxic shock syndrome (TSS) during menstruation, a case-control study was performed. Cases with onset between 1 January 1986 and 30 June 1987 were ascertained in six study areas with active surveillance for TSS. Age-matched controls were selected from among each patient's friends and women with the same telephone exchange. Of 118 eligible patients, 108 were enrolled, as were 185 "friend controls" and 187 telephone exchange-matched controls. Tampon use was a risk factor for developing TSS during menstruation (odds ratio = 29; 95% confidence interval = 7-120), and risk increased with increasing tampon absorbency (odds ratio = 1.34 per gram increase in absorbency; 95% confidence interval = 1.2-1.6). The role of tampon chemical composition could not be assessed because the number of cases was inadequate. Neither use of birth control pills for contraception nor use of medications for premenstrual or menstrual symptoms protected against or was a risk factor for the development of menstrual TSS. PMID- 2928653 TI - Normal vaginal microflora during use of various forms of catamenial protection. AB - Although the effect of vaginal tampons on microbial flora during menstruation has been studied, the effects attributable to particular tampon fibers have received inadequate attention. The purpose of this report is to review previous studies and describe the results of laboratory tests that compare the effects of use of various tampons on the normal changes that occur in vaginal microflora during menstruation. Tampon and swab samples were obtained from volunteers on days 2, 4, and 21 after the start of menses. Statistical evaluation of the qualitative and quantitative data revealed that the same numerically dominant phenotypes were present regardless of sample type, sample time, or catamenial product. In general, total bacterial counts decreased during menstruation, and the total bacterial counts from tampon samples tended to be lower than those in concomitant swab samples. Predictable changes in total numbers of the dominant species were noted when the data were evaluated by day of menstrual cycle. Results indicate that the tampon type had little effect on the qualitative and quantitative composition of the vaginal microflora during the menstrual cycle. PMID- 2928652 TI - Nonmenstrual toxic shock syndrome associated with barrier contraceptives: report of a case-control study. AB - Use of barrier contraceptives has been hypothesized to be a risk factor for nonmenstrual toxic shock syndrome (TSS). This association was evaluated in a case control study of nonmenstrual TSS; cases were identified through an active surveillance system for TSS during 1986 and 1987. Potential risk factors for nonmenstrual TSS were compared for 28 patients and 100 age-matched controls. Use of barrier contraceptives was associated with a significantly increased risk of nonmenstrual TSS, with matched odds ratios of 10.5 and 11.7 for contraceptive sponge and diaphragm use, respectively. Use of nonbarrier contraceptive methods was unrelated to nonmenstrual TSS. Despite the elevated odds ratio, the incidence of nonmenstrual TSS in barrier contraceptives users and the risk of nonmenstrual TSS attributable to barrier contraceptive use are low. Clinicians and women who use barrier contraceptives should be aware of this rare but potentially fatal complication; however, other considerations, such as efficacy and complications associated with other types of contraception, may be more important in the choice of a contraceptive method. PMID- 2928654 TI - Sequential assessment of vaginal microflora in healthy women randomly assigned to tampon or napkin use. AB - The effect of tampon usage on the vaginal microflora of 35 healthy women was determined following their random allocation to either tampon or napkin use for three consecutive menstrual cycles. Sequential and semiquantitative vaginal cultures were obtained on days 3 +/- 2, 15 +/- 2, and 25 +/- 2 of the menstrual cycle (day 1, first day of menses) before and after randomization. Before randomization, the rate of isolation and median counts of facultative lactobacilli were significantly higher (P less than .05) and that of eubacteria was significantly lower (P = .026) among regular tampon users than among exclusive napkin users. After randomization, only median counts of coagulase negative staphylococci were significantly increased (P = .025) during tampon use compared with the rates for the same women during napkin use. These shifts in vaginal microflora occurred only in samples obtained during menstruation and not in those obtained at other sampling times. The data presented here support the notion that the use of tampons may result in alterations in the autochthonous vaginal microflora. It remains to be determined if these ecologic shifts in the vaginal microflora may adversely affect resistance to colonization by potential pathogens in the lower female genital tract. PMID- 2928655 TI - Risk of developing toxic shock syndrome associated with toxic shock syndrome toxin 1 following nongenital staphylococcal infection. AB - Few risk factors for nonmenstrual toxic shock syndrome (TSS) have been identified. This study sought to determine at what rate and under what circumstances nongenital toxigenic Staphylococcus aureus infections led to TSS. Clinical isolates of S. aureus were examined for the production of TSS toxin 1 (TSST-1), and available sera from infected patients were tested for antibody to this toxin. Twenty-six percent of 810 isolates produced TSST-1. Isolates from children were more likely to be positive for TSST-1 than were those from adults. None of 57 patients with TSST-1-positive staphylococcal infection and a TSST-1 antibody titer of greater than or equal to 1:100 developed TSS. Eight of 65 tested patients with TSST-1-positive isolates had antibody below the presumably protective level of 1:100. Two of these patients had definite TSS, three had probable or possible TSS, and three probably did not have TSS. In patients lacking protective antibody to TSST-1, the interval between acquisition and infection with staphylococci, the type and amount of toxins produced, the site of infection, and still-unclarified aspects of host susceptibility may all affect the rate and severity of TSS. PMID- 2928656 TI - Distribution and expression of toxic shock syndrome toxin 1 gene among Staphylococcus aureus isolates of toxic shock syndrome and non-toxic shock syndrome origin. AB - Toxic shock syndrome toxin 1 (TSST-1), plays a significant role in the pathogenesis of TSS. TSST-1 production is subject to physiologic and environmental constraints. Thus, DNA probes that detect the chromosomal gene encoding the toxin are of value diagnostically, epidemiologically, and for studies of gene expression. Several synthetic oligonucleotide probes complementary to two regions of the TSST-1 gene were used to ascertain the presence of this gene in the chromosomal DNA of 261 strains of S. aureus from various TSS-related and non-TSS-related sources. Isolates were from clinically confirmed menstrual and nonmenstrual cases of TSS and from healthy vaginal carriers of S. aureus. Other strains tested included clinical non-TSS isolates and food poisoning-associated staphylococcal isolates. Detection of the TSST-1 gene by the labeled gene probes correlated in all but two cases with production of TSST-1. Ten Centers for Disease Control (CDC) strains that were isolated from TSS patients and did not produce TSST-1 were also examined, as were several strains of Staphylococcus epidermidis isolated from patients with suspected TSS. Neither group of strains possessed the TSST-1 gene. Finally, a 7-kilobase DNA restriction fragment of S. aureus containing the entire TSST-1 gene was transformed into Escherichia coli strains HB101 and DH5 alpha via a plasmid vector. PMID- 2928657 TI - [Advantages of single-dose treatment of vaginal Candida albicans infection]. AB - One-hundred forty women (60 pregnant and 80 non-pregnant women) with a history of Candida albicans infection were examined one month before treatment and were reexamined one month after treatment. Administration of a single agent consisting of 2,300 mg tablets of GynoTragoven (isoconazole nitrate, Schering, AG) resulted in immediate clinical improvement. One month after treatment, the success rate was 85-100 p. cent for non-pregnant women, and 83-100 p. cent for pregnant women. No side-effects were observed following therapy. According to studies published, a high percentage of infections develop during pregnancy, especially during the second (35 p. cent) and third (31.5 p. cent) trimesters. Because of the high rate of infections during pregnancy, preventive therapy should be considered during the final weeks of pregnancy, to prevent intrauterine infection during parturition. PMID- 2928658 TI - [Expulsion of arrested pregnancy product in the 2d trimester using a prostaglandin E1 analog administered intravaginally. Apropos of 12 cases]. AB - In this paper the authors report on the use of a prostaglandin E1 analog to expel fetuses stillborn in utero in the second trimester of pregnancy. Results of this clinical series make it possible to conclude on the efficacy of this agent and its simple utilization. Minor inconsequential side-effect observed coincide with the total absence of any complications. PMID- 2928659 TI - [Ureaplasma urealyticum and chorioamnionitis]. AB - 160 placentas from a clinical study group of women with pregnancy wastage and a control group were examined histologically and were cultured for Ureaplasma urealyticum. Recovery of Ureaplasma urealyticum was significantly higher in the pathologic group--43 p. cent--versus 21.6 p. cent in the control group, and was associated with chorioamnionitis. PMID- 2928661 TI - [Antenatal emergency call. Indications. Role of the SAMU (Medical Emergency Care Services)]. AB - The increased incidence of antenatal distress calls to the SAMU (emergency medical squad) by pediatric obstetricians in maternity departments (6 times in 5 years) poses the problem of recognizing their indications. Based on case reports of 128 newborns who profited from antenatal assistance, the authors attempt to define the indications. The elimination of student physicians in training for anesthesiology-intensive care, additional participants during SAMU transportation of patients, makes it even more necessary to define these indications accurately so that a single language of communication and procedure may be instituted for all who are involved in this effort. PMID- 2928660 TI - [Maternal behavior toward her newborn infant. Potential modification by peridural analgesia or childbirth preparation]. AB - The effects of sophrology and epidural analgesia on early relationship between the mother and her child were studied on a simple of 190 deliveries. The mothers were observed during and just after delivery. Mothers who had been separated from their child before the end of the observation were excluded from the study. The patients had the choice between epidural analgesia or prenatal care with sophrology. Participation to prenatal courses has statistically a positive effect on the relation between the mother and her child (p less than 0.01). Instead, epidural analgesia and posture have very limited effect on this factor. However, a trend to more interaction is found in multipari and patients who didn't choose epidural analgesia. PMID- 2928662 TI - [Psychotropics and pregnancy. Apropos of 2 case reports: the dose of triazolam]. AB - In this paper the authors report on two term-birth newborn infants who were exposed to long-term maternal treatment with benzodiazepines. They emphasize the free interval before the onset of respiratory pauses in these newborns, since triazolam is classified as belonging to the class of benzodiazepines with ultra rapid elimination and especially the severity of these disorders. PMID- 2928663 TI - [Age, gynecologic status and urinary stress incontinence]. AB - Based on a series of 1,000 female patients examined in office practice, the authors of this study seek to define the incidence of USI according to the patient's age gynecological status. Concerning age, this factor only has a clear effect in patients over 35 years of age. No significant difference in the incidence of USI was observed between sexually active women over 35, women approaching the menopause or post menopausal women; for this reason, the authors believe that in these cases, USI is related more to concomitant factors than to trophic lesions which however certainly are also present. During pregnancy, USI frequently occurs during the 2nd and 3rd trimesters; in contrast, in the first trimester of pregnancy, frequently there is increased intraabdominal pressure thus explaining why the incidence of USI is less than in sexually active women. PMID- 2928664 TI - [Patients with burns on both hands]. PMID- 2928665 TI - [Patients' autonomy]. PMID- 2928667 TI - [From the hospital to the home of the patient with respiratory insufficiency]. PMID- 2928666 TI - [Oxygen therapy at home]. PMID- 2928668 TI - [Falls in the elderly]. PMID- 2928669 TI - [Skin antiseptics]. PMID- 2928670 TI - [In the Caribbean]. PMID- 2928672 TI - [Use of a hydrocolloid dressing in the ambulatory treatment of burns]. PMID- 2928671 TI - [The nursing profession in France]. PMID- 2928673 TI - [The public sector. Let's chance it!]. PMID- 2928674 TI - [Private sector. Symptom: clinical]. PMID- 2928675 TI - [Hospital. Working conditions]. PMID- 2928676 TI - [All fire, all woman]. PMID- 2928677 TI - [Home care services. Nurses scour the country]. PMID- 2928678 TI - [From interim service to industry]. PMID- 2928679 TI - [And yet ... one continues]. PMID- 2928680 TI - [Legislation and collective bargaining]. PMID- 2928681 TI - Antitrust alert. PMID- 2928683 TI - The nursing shortage: a professional's viewpoint. PMID- 2928682 TI - Success of contact chemolysis in calcified cholesterol gallstones. AB - Contact dissolution of cholesterol gallstones has emerged as a viable alternative in patients at high risk for surgery. The newest dissolution agent methyl tertiary butyl ether (MTBE) has undergone a series of successful clinical trials and has compared favorably with its predecessor, monooctanoin (MO). Previous studies have demonstrated the utility of MTBE in the setting of a large solitary gallstone impacted within the cystic duct as well as with multiple non obstructing gallstones. We present a case of MTBE contact dissolution in the face of combined non-obstructing and obstructing gallbladder calculi. Whereas others have recommended restricting its use to those gallstones that are radiolucent, we have shown that MTBE may be used, and excellent results obtained, even with calculi that are calcified, so-called "Type 1" cholesterol gallstones. PMID- 2928684 TI - DHHS Office of Inspector General: an overview. PMID- 2928685 TI - Status of the Rhode Island Board of Medical Licensure and Discipline. PMID- 2928687 TI - Screening criteria for prior authorization for ten surgical procedures. PMID- 2928686 TI - Protecting physicians' rights in disciplinary proceedings. PMID- 2928688 TI - Publish and protect. PMID- 2928689 TI - Copper histochemistry of 5 murine tumors and their respective metastases. AB - Tissue copper content has been evaluated in 4 murine mammary adenocarcinomas, 1 murine lung adenocarcinoma and their respective metastases. Histochemical techniques have been used to analyze copper distribution in tumor tissues. It is observed that the degree of copper staining is inversely related to tumor differentiation. As the copper level reflects one of the metabolic changes in the host carrying the tumor, it is suggested that it could be used as a good marker for tumor differentiation. PMID- 2928690 TI - Martyrs send the wrong messages. PMID- 2928692 TI - A nursing response to the teen pregnancy epidemic. PMID- 2928691 TI - Facing down the fear of public speaking. PMID- 2928693 TI - Be ready for Lyme disease in your own backyard. PMID- 2928694 TI - Chest pain: your response to a classic warning (continuing education credit). PMID- 2928695 TI - Will your patient survive that trip to x-ray? PMID- 2928696 TI - Diabetes now--the role of diet and drugs (continuing education credit). PMID- 2928697 TI - The hip: nursing fracture patients to full recovery. PMID- 2928698 TI - The hip: when the joint must be replaced. PMID- 2928699 TI - A winning team. PMID- 2928700 TI - Let's put an end to malpractice panic. PMID- 2928701 TI - AIDS, confidentiality, and lab requisitions. PMID- 2928702 TI - Hypoglycemia: separating facts from fads. PMID- 2928703 TI - Health for all: are we achieving it? PMID- 2928705 TI - Midwifery as a specialty of nursing. PMID- 2928704 TI - Managing pain. PMID- 2928706 TI - The changing context of prenatal education. PMID- 2928707 TI - On the inside: Rep program bridges the gap between RNABC and nurses in the workplace. PMID- 2928708 TI - [Diagnosis of unusual fractures of the wrist bones]. AB - Fractures of the navicular bone are the most frequent fractures in the region of the wrist bone. Injuries of the other carpal bones are often primarily overlooked, since the examiner commands over less routine in diagnosing these rare fractures and the carpal bones are often superimposed over one another. We examined 9.723 x-ray films of the hand performed because of suspected fracture of the os naviculare, in order to find out how often lesions of the carpal bones - with the exception of those of the scaphoid bone - were discovered via the x-ray series of the os naviculare manus. For each individual wrist bone we recorded the incidence of fractures, clinical treatment and diagnoses, including any special x ray takes that would be necessary for the detection of a particular fracture. PMID- 2928709 TI - [Incidence and clinical importance of chronic reactive periosteal new bone formation in the cervical region in patients with differing neurologic symptomatology]. AB - 81 patients classed into three groups with clinical evidence of neurological symptoms and posttraumatic pain of the cervical spine and the incidence of degenerative disorders were studied noninvasively via CT scanning. Imaging of osseous structures in the axial plane by CT was excellent in all cases, even in the lower part of the cervical spine where soft-tissue discrimination is often impossible because of shoulder artifacts. In about half of the patients with nerve-root symptomatology as well as with signs of involvement of long tracts, narrowing of the foramen intervertebral, respectively of the spinal tract, was seen, attributable to degenerative osseous apposition with excellent clinical segmental and (according to radicular symptoms) side correlation. In contrast to these results the group of patients with posttraumatic clinical symptoms showed almost 50 per cent less preexisting degenerative disorders of the cervical spine. In conclusion, we assume that high-grade osseous appositions of the dorsal part of the vertebral body play an important role in the development of radicular symptomatology and cervical myelopathy, respectively. Hypertrophic changes of the processus articularis with narrowing of the spinal canal occurred in 14 per cent and were therefore of minor clinical significance. PMID- 2928710 TI - [Ulcerative angiosarcoma of the cranial vault masquerading as a pyoderma]. AB - This is a report on a patient suffering from a progressive ulcerative tumour of the vault of the cranium with accompanying osteolytic destruction. The disease pattern was interpreted first after a biopsy from the marginal wall of the inflammation as a case of pyoderma. It was only on postmortem examination that an angiosarcoma of the ulcerative type was correctly diagnosed. The ulcerative type of angiosarcoma is sometimes difficult to differentiate from inflammatory skin diseases. PMID- 2928711 TI - [Conventional and computed tomographic findings in polysplenia syndrome]. AB - A case of polysplenia syndrome associated with abdominal situs inversus and anomalies of the inferior vena cava system is demonstrated by conventional and CT examinations. The conventional radiographic findings already suggest the diagnosis; final verification can be achieved via computed tomography. PMID- 2928712 TI - [Perforation of the right ventricle during pulmonary angiography: possible causes and their prevention]. AB - This is a report on a perforation of the myocardium during pulmonary angiography. The choice of the catheter is very important for the occurrence of such complications. We used a Cook 7 French polyethylene multipurpose catheter, which did not guarantee sufficient stabilisation due to its small number of side holes during injection of contrast medium. On the other hand the straight top of the catheter promoted its penetration into the myocardium. To avoid such often lethal complications, catheters with pigtail configuration should be used. PMID- 2928713 TI - [Glaucoma: detection and therapeutic indications]. AB - Glaucoma screening requires a good knowledge of the epidemiology and risk factors of this disease. So, we measure the intraocular pressure, analyse the visual field and examin the optic nerve head by ophtalmoscopy. Other investigations have been described, allowing early treatment. Some medications are active on aqueous humor production, others on outflow but side effects are often observed. Laser therapy is an alternative to surgery. PMID- 2928714 TI - [Cataract surgery in 1989]. AB - Cataract is a very common disease, but making this diagnosis does not necessarily mean that surgery is always required. The indications for surgery depend on the patient's age, on the activity of the lesion and on the functional repercussions of the opacity of one or two eye lenses. The best operation is the insertion of an artificial lens, knowing that it has now very few contra-indications. With modern surgical techniques, functional recovery is very rapid, convalescence extremely short, and day surgery may even be considered. PMID- 2928716 TI - [Conjunctival capillaroscopy]. AB - Microcirculation is clearly visible and can be observed on the conjunctival mucosa by means of any microscope and notably with the slit lamp microscope of ophtalmologists. A glance at the conjunctival vessels may provide useful information on the quality of microcirculation generally and on the ischaemic or oedematous repercussions of lesions affecting the kidney, the brain and other organs. The vascular alterations detectable on the conjunctiva are described. The retina also may present with abnormalities of microcirculation. Their easy detection on the conjunctiva should lead to a more complete ophthalmic and systemic exploration. PMID- 2928715 TI - [Benign corneoconjunctival pathology]. AB - Benign diseases of the cornea and conjunctiva can in fact be found in all chapters of pathology. Inflammatory diseases are by far the most common, with a predominance of viral infections, notably herpes corneae the long-term prognosis of which is not always favourable. Other benign diseases are injuries, dystrophies, overloads and finally tumours. All these diseases are briefly described in this article. PMID- 2928717 TI - [Recurrent oxalo-calcium lithiasis. 1: Epidemiology, composition and theories of calculi formation: crystallization factors]. PMID- 2928718 TI - [Corneal refractive surgery]. AB - During the past 8 years surgery of the cornea for refractive errors has risen to the rank of an independent, specialized discipline. It covers a range of techniques devised to correct or reduce all types of ametropia. Radial keratotomv is the operation most frequently performed to correct mild or moderate myopia from -1 to -6 diopters. Keratomileusis with or without freezing is a more complex procedure used to correct severe myopia of -8 to -16 diopters. Epikeratophakia for myopia or hypermetropia has a wider range of correction, ranging from 5 to 30 diopters. Each of these techniques has its own possibilities, limitations and risks. The main problem in this type of surgery if the predictability of its results. It is indicated essentially for cases where contact lenses have proved useless or are contra-indicated. PMID- 2928719 TI - Effect of bicarbonate, acetate, and citrate on water and sodium movement in normal and cholera toxin-treated rat small intestine. AB - Bicarbonate, citrate, or acetate are commonly included in oral rehydration solutions to correct acidosis and possibly because of their ability to promote water and sodium absorption. We have investigated the effect of these anions on water and sodium transport in normal and also in secreting (cholera toxin treated) rat small intestine using a single-pass perfusion technique. In normal jejunum bicarbonate and acetate produced net absorption, and citrate net secretion of both water and sodium. In normal ileum all anions produced net absorption of water and sodium. In the secreting jejunum, however, bicarbonate had no effect on water and sodium secretion, whereas acetate and citrate actually enhanced the secretory state for both water and sodium. None of these anions had any effect on water and sodium secretion in the ileum. These observations suggest that normal and secreting intestine are qualitatively different with regard to handling of these organic anions. The addition, therefore, of bicarbonate, acetate, or citrate to oral rehydration solutions may have no beneficial effect with regard to the promotion of water and sodium absorption in the secreting intestine during acute diarrhoeal states and could actually be deleterious. PMID- 2928720 TI - Spontaneous anorectal pressure activity. Evidence of internal anal sphincter contractions in response to rectal pressure waves. AB - To characterize spontaneous anorectal pressure activity and a possible relation between the activity in the rectum and the anal canal, 11 healthy female volunteers were investigated. Resting activities were obtained during 1-h recordings with a multi-channel perfused catheter measuring the pressure 1, 2, 3, 7, and 8 cm from the anal verge. In five subjects sequences of rhythmic rectal pressure waves with amplitudes exceeding the maximal anal resting pressure coincided with a similar internal anal sphincter activity, preventing rectal pressure from exceeding the anal pressure at any point. The mean frequency was 5 x min-1 (range, 3-6 x min-1). This may well be a reflex mechanism by which the internal anal sphincter prevents incontinence in the resting state. Low-frequency pressure waves, not previously described, were detected in four women. These pressure waves were attributed to the internal anal sphincter and were named ultra-slow waves type II. The mean frequency and amplitude were 0.16 x min-1 (range, 0.15-0.17 x min-1) and 24 cm H2O (range, 11-41 cm H2O), respectively. The function of these pressure waves is unknown. PMID- 2928721 TI - Blood transfusion and prognosis in colorectal carcinoma. AB - The association of perioperative blood transfusion and cancer recurrence was analyzed in a 10-year series of 520 patients with colorectal carcinoma undergoing curative surgery. Cancer recurrence was observed in 35 of 165 (19%) non transfused and in 119 of 355 (34%) transfused patients (p less than 0.001). A significant difference in favor of the non-transfused group was also evident in cases of colonic (p less than 0.05) and rectal (p less than 0.01) tumors separately. The transfused group had both more recurrences and higher mortality. Although there were no differences in age, sex, and Dukes's stage between the two groups, further analysis showed other significant variables explaining the different result. First, there were significantly more patients with rectal cancer in the transfused group. In addition, emergency operations for obstruction and resections of adjacent organs for tumor invasion were significantly commoner in transfused patients. Exclusion of such patients and those with small tumors excised locally per anum resulted in the disappearance of the prognostic difference between the transfused and non-transfused groups (marginally significant difference in rectal carcinoma; p = 0.05). It is concluded that the seemingly adverse effect of blood transfusion on the prognosis of colorectal carcinoma may largely be explained by other associated variables. PMID- 2928722 TI - Intestinal permeability assessed with different-sized polyethylene glycols in children undergoing small-intestinal biopsy for suspected celiac disease. AB - The gastrointestinal permeability was assessed by means of an oral load of a mixture of different-sized polyethylene glycols (PEG 400 and PEG 1000) in 76 children undergoing small-intestinal biopsy because of suspected celiac disease. Children with a mucosal abnormality suggestive of celiac disease had a lower urinary recovery of larger PEG molecules. They also displayed an altered permeability barrier, as evidenced by a lower ratio of recovery between large (1074 Da) and small (370 Da) PEG molecules. Gluten elimination and gluten challenge caused a significant change in PEG recoveries in children undergoing repeated PEG tests. Repeated assessments of intestinal permeability by means of different-sized PEGs after gluten withdrawal and challenge could complement or indicate suitable time for performing small-intestinal biopsy in children with gluten intolerance. PMID- 2928723 TI - Rectosigmoid motility response to sham feeding in irritable bowel syndrome. Evidence of a cephalic phase. AB - Rectosigmoid pressure recordings by means of open-ended perfused catheters were performed on 21 patients with the irritable bowel syndrome (IBS). Motility indexes were calculated in resting conditions, after sham feeding, after a meal, and after 0.5 mg neostigmine intravenously. Each step of stimulation caused a significantly increased motility index compared with the previous step (p less than 0.01). The increase in rectosigmoid pressure activity after sham feeding indicates the existence of a cephalic phase in the postprandial motor response of the colon in IBS. PMID- 2928724 TI - Primary biliary cirrhosis: clinical features and outcome, with special reference to asymptomatic disease. AB - The clinical features and outcome of primary biliary cirrhosis (PBC) during long term follow-up study (mean, 9 years; range, 1-20 years) was reviewed in 80 patients. Seventy per cent were asymptomatic at initial presentation. The mortality in the symptomatic group was 63%, compared with 20% in the asymptomatic group (p less than 0.001). The presence of hepatomegaly and histopathology consistent with stage 2-4 in asymptomatic cases was a prognostically ominous sign, as these patients often developed symptoms (p less than 0.001). The finding of histopathology consistent with stage 1, however, was correlated with an excellent prognosis with respect to both symptoms and mortality. Only 11% of these stage 1 patients became symptomatic, and none died (p less than 0.001). The mean age of symptomatic and asymptomatic patients did not differ. Moreover, the age distribution of asymptomatic patients with early histopathology and those patients with more advanced histopathology did not differ. This may indicate that asymptomatic PBC consists of subgroups with an active disease of various degrees. PMID- 2928725 TI - Wedged hepatic venous pressure recording and venography for the assessment of pre cirrhotic and cirrhotic liver disease. AB - Wedged hepatic venous pressure recording and venography were investigated to assess histologic reflection of the stage of chronic liver disease. Forty-nine patients were studied. The four main groups and the means of the pressure gradients (WHVP - FHVP) with their 95% confidence limits were chronic active hepatitis (n = 12), 6 mm Hg (4.35-7.65); chronic hepatitis in transition to cirrhosis (n = 9), 10.3 mm Hg (6.6-14.1); and established cirrhosis (n = 8), 15.4 mm Hg (9.4-21.4); but only 3.4 mm Hg (2.2-4.6) in near-normal liver (n = 8). A pressure gradient of more than 5 mm Hg was always associated with significant liver disease on liver biopsy. In 25 patients venographies were assessed. Whereas patients with near-normal biopsy specimens had normal appearances, patients with more severe disease showed increasingly severe changes. The techniques applied should not replace liver biopsy. However, they provide relevant supplementary information, might have a place in follow-up studies to assess progression of disease, and occasionally reduce the need for liver biopsy. PMID- 2928727 TI - The contribution of the diaphragm and an intrinsic sphincter to the gastroesophageal antireflux barrier. An experimental study in the dog. AB - The components of the mechanical gastroesophageal antireflux barrier were studied in anesthetized dogs (15-18.5 kg). Pressure in the gastroesophageal junction area was recorded by pull-through manometry (using an infused end-hole-provided catheter) during gastric filling (distension) with water. In addition, the gastric volume at which reflux occurred was used as a measure of function and competence. Each dog was studied while intact and spontaneously breathing, after muscle relaxation, after excision of the left half of the diaphragm, and after death. In the intact dogs a barrier with a mean resting pressure of 20 (range, 14 26) cm H2O was recorded. During gastric filling the barrier pressure initially increased to 32 (16-42) cm H2O before steadily decreasing until reflux occurred. The highest pressure was recorded with 625 ml (250-1500 ml) in the stomach. Reflux occurred at a gastric volume of 3200 ml (2300-4000 ml). Muscle relaxation changed neither resting pressure nor reflux volume significantly. After excision of the left half of the diaphragm a barrier with a resting pressure of 15 (6-22) cm H2O was still recorded. Reflux then occurred at a gastric volume of 1400 ml (500-2500 ml). In dead dogs no pressure barrier could be recorded, and reflux was provoked already by 500 ml (250-750 ml) in the stomach. The presence of a mechanical barrier also after excision of the left half of the diaphragm, as evidenced by both pressure and reflux volume, can only be explained by an intrinsic sphincter, a lower esophageal sphincter (LES). However, the experiments also showed that the diaphragm contributed to the competence of the LES. This contribution was at first passive. PMID- 2928726 TI - Fat and pancreatic secretion. AB - In 10 healthy volunteers we investigated the effects of intraduodenal oleic acid at various concentrations (0-40 mM) and at various degrees of emulsification on pancreaticobiliary secretion and the release of secretin and cholecystokinin (CCK) into plasma. We found that the release of the two hormones was directly related to the dose of fat and to the degree of emulsification. The threshold of CCK release (and amylase output) was low in comparison with the threshold for secretin release (and bicarbonate or volume output). When the degree of emulsification of the fat was increased, no simple relation was observed between hormone levels and pancreatic exocrine secretion. The output of bile salts was identical at various fat concentrations. We conclude that both secretin and CCK are dose-dependently released by emulsions of oleic acid in normal man and that the thresholds for release are probably different. PMID- 2928728 TI - Oesophageal motility and lower oesophageal sphincter competence in progressive systemic sclerosis and localized scleroderma. AB - Oesophageal motility and lower oesophageal sphincter (LOS) competence were investigated in 13 patients with progressive systemic sclerosis (PSS) and in 16 patients with localized scleroderma (LS) by means of oesophageal manometry and 24 h pH monitoring of the distal oesophagus. Results were compared with those of a control group consisting of asymptomatic volunteers. Marked abnormalities in oesophageal motility and in acid exposure in the distal oesophagus were observed in PSS patients only. The mean resting pressure of the LOS was 10.1 +/- 1.5 mmHg in PSS, 21.4 +/- 1.1 mmHg in LS, and 23.8 +/- 2.0 mmHg in asymptomatic controls. Overall sphincter length was 24.1 +/- 3.4 mm in PSS, 31.1 +/- 1.6 mm in LS, and 39.0 +/- 2.0 mm in the control group. Spincter abdominal length was 12.1 +/- 2 mm, 15.4 +/- 1 mm, and 25.0 +/- 1 mm, respectively. The amplitude and duration of oesophageal waves were markedly reduced at 5, 10, and 15 cm above the LOS in PSS patients, with only the upper part of their gullet being spared. An abnormal acid exposure in the distal oesophagus was observed in 84.6% of PSS patients, whereas only 18.2% (2 of 11) of pH-tested LS patients had an abnormal 24-h pH test. These data show that a marked oesophageal involvement is present only in the systemic form of scleroderma. Oesophageal tests may be useful for a circumstantial diagnosis whenever the diagnosis of PSS is uncertain; however, their use does not seem to be justified as routine in patients with LS. PMID- 2928729 TI - Endoscopic findings and diagnoses in unselected dyspeptic patients at a primary health care center. AB - This study reports the findings on endoscopy and the final diagnoses of 172 consecutive patients with dyspepsia from a primary health care center. The purpose of our study was to carry out a thorough gastroenterologic investigation of all patients consulting their general practitioner and reporting dyspepsia during 1 full year, from a population within a defined geographic area. The examinations included patient history, physical examination, laboratory tests, esophagogastroduodenoscopy (EGD), and sigmoidoscopy. All the examinations, including the EGDs, were done at the primary care center. A final diagnosis was settled after a minimum of 6 months. Six per cent had esophagitis, 13% had peptic ulcer disease, 1% had gastric cancer, and 1% had irritable bowel disease. Completely normal endoscopies were seen in 19%. No patient had villous atrophy. Sixty-four per cent had non-ulcer dyspepsia, and 26% had inflammatory bowel syndrome, with great overlapping. It is concluded that open-access endoscopy is a valuable service to primary care, the result of which greatly enhances the diagnostic accuracy in dyspeptic patients entering primary care. PMID- 2928730 TI - The effect of vasoactive intestinal peptide, secretin, and glucagon on human duodenal bicarbonate secretion. AB - Duodenal luminal acidification increases duodenal mucosal bicarbonate production and also releases both secretin and vasoactive intestinal peptide (VIP). The effect of these two structurally similar peptides on human duodenal bicarbonate production has not been examined in humans. Our purpose was therefore to assess the effect of VIP and secretin and also glucagon, a homologous hormone, on human duodenal bicarbonate secretion. A 4-cm portion of either proximal or distal duodenum was isolated and perfused with iso-osmolar NaCl. Pure porcine VIP (200 and 400 pmol/kg-h intravenously) significantly increased proximal duodenal bicarbonate secretion. Although secretin (0.01 to 0.18 CU/kg-h intravenously) markedly increased pancreatic bicarbonate secretion, it failed to alter duodenal mucosal bicarbonate output in either the proximal or the distal duodenum. Glucagon (1 to 8 micrograms/kg-h intravenously) did not affect proximal duodenal mucosal bicarbonate output. It is concluded that VIP, but neither secretin nor glucagon, significantly stimulates human duodenal mucosal bicarbonate secretion. PMID- 2928731 TI - The final outcome of patients presenting with their first episode of acute diarrhoea and an inflamed rectal mucosa with preserved crypt architecture. A clinicopathologic study. AB - When a patient presents with acute diarrhoea, the most important question is whether it represents the first episode of chronic inflammatory bowel disease (CIBD) or acute self-limited colitis (ASLC). The early changes in the rectal mucosa of patients with ASLC have been claimed to be highly diagnostic, the presence of an unspecific inflammatory infiltrate in the lamina propria and the absence of disturbances in the crypt architecture being the characteristic features. Thirty-two patients who in the period 1980-1984 presented with their first episode of acute diarrhoea and whose rectal mucosa showed these histologic features were followed up for 1.5-7 years. Forty-one per cent of the patients were finally classified as having ASLC and 28% as having diseases other than CIBD or ASLC. Thirty-one per cent eventually developed CIBD. Thus the features claimed to be diagnostic of ASLC could not predict the final outcome of the disease in patients presenting for the first time with acute diarrhoea. The histologic interpretation can provide significant information in these patients but should never replace a careful clinical judgement and, if doubt remains, further observation of the patients. PMID- 2928732 TI - Natural history of duodenal ulcer detected by the gastric mass surveys in men over 40 years of age. AB - In a gastric mass survey with photofluorography performed on 10,605 male office workers over 40 years of age, 456 cases of duodenal ulcer (4.3%) were detected. These cases were scheduled to be followed up every 6 months with endoscopy and without any anti-ulcer drugs. Two hundred and seventy-six of the cases, including 169 cases with craters and 107 cases with scars, were followed up for 2 years. Forty-one of 169 craters (24.3%) had healed, and 21 of 107 scars (19.6%) had relapsed at 6 months. At 24 months 36 of 169 craters (21.3%) had healed, and 31 of 107 scars (29.0%) had relapsed. Sixty-four and a half per cent of the ulcers that showed crater at entry remained at the crater stage, and 62.6% of ulcer scars at entry remained healed at every endoscopy during the trial period. With regard to the cases' background, cigarette smoking adversely affected the natural history of the duodenal ulcer. However, years after onset, previous treatment, history of overt bleeding, and alcohol and coffee consumption did not affect the present ulcer activity. PMID- 2928733 TI - Anal sphincter function after colectomy, mucosal proctectomy, and ileoanal anastomosis. AB - Anal sphincter investigations were performed in 41 patients with straight ileoanal anastomosis and in 10 controls. In 20 patients (group I) the mucosal stripping had been performed from the abdominal side, leaving 1-2 cm of distal anal mucosa. In 21 patients (group II) the anal mucosa had been stripped from the perineal side as far as the dentate line. Continence was perfect in all patients in group I and poor in 6 of 17 patients in group II, when examined 12 months after the operation. Anal canal resting pressure was normal in group I. In group II the resting pressure was significantly decreased and correlated to continence function. The maximum anal canal squeeze pressure was the same in the two groups. The slope of the regression line between pressure rise and integrated electromyography proved to be a useful criterion of the external anal sphincter function and was significantly correlated to degree of incontinence. This variable was significantly smaller in group II patients than in group I and controls. Thus, function of the anal sphincters was normal after mucosal proctectomy performed from above with preservation of a mucosal brim. Dysfunction of the internal and external anal sphincter was found after perineal mucosal dissection and was correlated to continence function. PMID- 2928735 TI - The mechanism of acute gastric ulcer after induced hemorrhagic shock. AB - Changes in gastric mucosal blood flow were investigated for their relationship to gastric mucosal prostaglandin E2 (PGE2) and noradrenaline (NA) in rats with hemorrhagic shock. The results were as follows: 1) Gastric mucosal blood flow and NA decreased after hemorrhage. Gastric mucosal PGE2 initially increased after exsanguination and then markedly decreased. 2) Administration of NA before hemorrhage resulted in an increase of PGE2. However, the PGE2 value for animals receiving NA after hemorrhage was not different from that of non-NA-treated group. 3) Pre-treatment with PGE2 suppressed the reduction in both gastric mucosal blood flow and NA and the development of ulcer. These results suggest that the increase in gastric mucosal PGE2 in the early stage of shock might represent a phenomenon of adaptation by the adrenergic activation, and the decrease in PGE2 in the late stage might result from impaired synthesis of PGE2 due to persistent hypoxia and might be one of the possible factors in ulcer formation. PMID- 2928734 TI - A randomized comparison of horizontal and vertical banded gastroplasty: what determines weight loss? AB - Pouch volume, stoma diameter, and pouch emptying rate were measured postoperatively and after 6 months in 45 morbidly obese patients who had been assigned to either horizontal gastroplasty (HGP) or vertical banded gastroplasty (VBGP) after pretreatment with diet alone. Pouch volume and stoma diameter were measured by a standardized radiographic method with blinded assessment by two observers. Pouch emptying rate was determined by a standardized scintigraphic method and expressed as the mean transit time (t60). Pouch volume and stoma diameter did not change, whereas t60 decreased by 36% during the first 6 months after HGP (p less than 0.001). Pouch volume was larger after HGP (p less than 0.001). Pouch emptying was faster after VBGP (p less than 0.001), but these patients had the better weight loss (p less than 0.001). Variation in weight loss after either operation was unrelated to pouch volume, stoma diameter, and t60. Stoma diameter was not correlated with t60. The study provides further evidence against the significance of stoma diameter and pouch emptying rate as determinants of weight loss after gastroplasty. The much smaller pouch volume after VBGP may favor weight loss. PMID- 2928736 TI - Endoscopic, portographic, and hemodynamic evaluation of prolonged propranolol administration in pigs with experimental portal hypertension and esophageal varices. AB - The effect of long-term propranolol administration on esophageal varices, portocollateral shunting, portal pressure, hepatosplanchnic hemodynamics, and liver function was studied in a pig model with experimentally induced prehepatic portal hypertension and esophageal varices. Five pigs were treated with 160 mg propranolol daily from week 5 to week 24 after portal-vein banding, and five pigs served as nontreated controls. Administration of propranolol caused an initial, significant reduction (20%) of portal venous pressure, followed by a gradual increase to levels not different from control pressures. In contrast, a marked reduction of the caliber of the coronary vein and size of the esophageal varices was noticed. Twenty weeks of propranolol treatment did not change liver blood flow or liver function. We conclude that the size of the varices rather than portal venous pressure depicts the effect of propranolol treatment and suggest that the beneficial effect of propranolol on variceal bleeding can be explained by a reduction in the wall tension of the varices, initiated and maintained by a diminution of splanchnic blood flow. PMID- 2928737 TI - Characterization of hepatic hemodynamics in cirrhotics and non-cirrhotics. Effect of glucagon infusion. AB - The effect of glucagon on hepatic regional hemodynamics was investigated in patients with chronic liver disease during peritoneoscopy with reflectance spectrophotometry. When glucagon was infused intravenously in patients with a non cirrhotic liver, the regional hepatic tissue oxygen consumption, as estimated spectrophotometrically, increased significantly, whereas the index of hepatic tissue blood volume did not change appreciably, and consequently, the oxygen saturation of hemoglobin in the hepatic tissue blood decreased. In contrast, the administration of glucagon in patients with liver cirrhosis resulted in a significant increase in the index of hepatic tissue blood volume and produced a minor increase in hepatic tissue oxygen consumption. The oxygen saturation of hepatic blood hemoglobin tended to increase in the cirrhotics. The result suggests the presence of functional vasoconstriction at the presinusoidal and/or sinusoidal vessels in the cirrhotic liver, possibly due to a decreased vasomotor activity and/or an abnormal regulatory function of vasoactive substances, which are released by glucagon. PMID- 2928738 TI - Enzyme activities in the duodenal mucosa in duodenal ulcer patients. AB - The mucosal enzyme activities of 11 marker enzymes from the brush border, basolateral membrane, and lysosomes of 45 patients with an active duodenal ulcer (DU) were determined by analysis of homogenized biopsy specimens obtained from the duodenal bulb and descending duodenum at endoscopy. They were compared with activities measured in 22 controls. In the duodenal bulb lactase (p less than 0.005), neutral-alpha-glucosidase (p less than 0.0005), and monoamine oxidase (p less than 0.0005) were significantly decreased in DU patients. In the descending duodenum all the brush border enzymes except sucrase were significantly decreased when compared with controls. DU patients with inflammation in the biopsy specimens from the duodenal bulb had decreased levels of lactase (p less than 0.05), sucrase (p less than 0.05), neutral-alpha-glucosidase (p less than 0.05), leucyl-beta-naphthylamidase (p less than 0.05), and acid phosphatases (p less than 0.05) when compared with DU patients with normal histology in this region. In the descending duodenum the activities of leucyl-beta-naphthylamidase (p less than 0.05) were decreased in patients with inflammation compared with those without such histologic changes. DU patients who had taken antacids before the investigation had decreased activities of lactase (p less than 0.05) in the descending duodenum when compared with those who had not taken antacids. Activities of lactase (p less than 0.005), sucrase (p less than 0.005), neutral alpha-glucosidase (p less than 0.05), and acid beta-glucuronidase (p less than 0.0005) in the descending duodenum were significantly lower in smokers than in non-smokers with active DU. PMID- 2928739 TI - Gastric emptying and gastrointestinal symptoms in patients with atrophic gastritis and the effects of domperidone. AB - The relationship of gastric emptying of liquid to the extent of fundal gastritis and gastrointestinal symptoms was investigated in a total of 37 subjects comprising healthy controls with no gastrointestinal symptoms and patients with constant gastrointestinal symptoms for at least 1 year. Gastric emptying was measured by the acetaminophen absorption method, and the extent of fundal gastritis was determined by the endoscopic Congo-red test developed at this hospital. Gastric emptying was significantly slower in patients with gastrointestinal symptoms than in healthy subjects. It was also significantly slower in patients with than in those without severe fundal gastritis. Gastrointestinal symptoms were significantly more frequent in patients with delayed gastric emptying. The acute effect of oral administration of domperidone on gastric emptying was examined. A single dose of domperidone (20 mg) significantly increased the rate of gastric emptying. PMID- 2928740 TI - [Comparison of a sensitive rabbit brain thromboplastin and a human placenta thromboplastin for thromboplastin time determination]. AB - Prothrombin times were measured in 120 orally anticoagulated patients and 122 patients not orally anticoagulated using two different commercial thromboplastin reagents, a rabbit brain thromboplastin (CRB-Thromboplastin, Roche) and a human placenta thromboplastin (Thromborel S, Behring). A good correlation (r = 0.93, slope = 1.089, intercept = 0.014) was found between the International Normalized Ratio (INR) values of the anticoagulated plasmas obtained with both thromboplastins. Defining five degrees of intensity of anticoagulation (between INR less than or equal to 2.0 to INR greater than or equal to 5.1) the intensity of treatment was judged concordantly with both thromboplastins in 67% of the patients and as differing by one degree in 32%. In only one out of 120 patients was a larger discrepancy of INR values found. - A good correlation (r = 0.93) was also found between the prothrombin times expressed as Quick percentage values as assessed with both thromboplastins in 122 patients not orally anticoagulated. In 82 cases a "normal" prothrombin time (Quick greater than or equal to 70%) and in 33 cases a "subnormal/diminished" percentage value (Quick less than 70%) was obtained with both thromboplastins. In only 7 out of 122 plasma samples was the Quick percentage normal with one and subnormal with the other reagent. - The good conformity of the INR values measured with two thromboplastins of differing species but similar sensitivity (International Sensitivity Index [ISI] = 1.14 for CRB-Thromboplastin, and = 1.10 for Thromborel S) supports the recommendation by the World Health Organization that the intensity of oral anticoagulation be expressed in terms of INR. Whether INRs obtained with thromboplastins of largely differing ISIs show sufficient conformity will need to be assessed by further prospective studies. PMID- 2928742 TI - [Unusual manifestations of Q fever disclosing hairy cell leukemia]. AB - An unusual case of Q fever in a 62-year-old female is described. The patient presented with severe pneumonia and developed renal failure, disseminated intravascular coagulation and pancytopenia which recurred after antibiotics were discontinued. Subsequently hairy cell leukemia was diagnosed and evolved favorably under treatment with doxycycline and alpha-interferon. A review of the literature confirms that renal failure and disseminated intravascular coagulation do not appear to be associated with Coxiella burnetti infections, nor has the association of Q fever and hairy cell leukemia been previously described. PMID- 2928741 TI - [Successful clonidine treatment of restless leg syndrome in chronic kidney insufficiency]. AB - Restless legs syndrome is a common and sometimes incapacitating disorder in chronic uraemic patients. While therapeutic concepts have so far been disappointing, there have been recent reports on the favourable effect of clonidine in non-uraemic patients with symptoms of restless legs syndrome. Therefore, a double-blind study was conducted in 20 patients with chronic renal failure (11 conservatively treated, 9 on RDT) and symptoms of restless legs. 10 patients were treated with 0.075 mg clonidine twice daily and 10 received placebo. The patients were investigated 3 days after starting therapy. - In the clonidine-treated group complete relief of symptoms was noted in 8 out of 10 patients, a striking alleviation in one, while in one further patient the symptoms remained unchanged. In contrast, only one of 10 patients in the placebo group had a mild alleviation of symptoms. Blood pressure did not differ significantly in the two groups. The data show that low-dose clonidine administration is a very effective approach in the treatment of the restless legs syndrome in chronic uraemic patients. PMID- 2928743 TI - [Oral health--the status of knowledge 1985. An analysis of a repeated survey of 761 Swiss recruits]. AB - Concurrent with an epidemiological study, 761 military recruits were questioned about their attitudes towards dentists, dental treatment and oral hygiene habits. In addition, their knowledge of periodontal diseases and their prevention was evaluated, as were their smoking and snacking habits. Such recruits had been similarly questioned 11 years previously. Both the present and the previous studies showed that the recruits had a very positive attitude towards their dentitions, expressing a defined desire for good oral health. Oral hygiene habits, particularly daily toothbrushing, improved during the decade and were graded as acceptable. However, the recruits generally had a poor impression of dentists and their individual treatments. The number of recruits presenting for the emergency treatment of pain increased by 20%. Of this group, recruits who only sought dental checkups sporadically increased four times compared to the previous study. Confirming results of the previous study, knowledge of periodontal diseases and its prevention were poor. This may indicate a lack of clearly explained information by the dental teams which previously and presently treated these recruits. The development of a consumer society was expressed by the increased snacking habits. In contrast to what was expected, the information about dental diseases and the motivation of recruits by dental personnel and in the schools to better dental health should be improved. PMID- 2928744 TI - [Urinary excretion of fluorides in schoolchildren of Lausanne and Geneva in relation to salt fluoridation]. AB - Urinary excretion of fluoride and sodium and urinary flow were studied in 230 schoolchildren (average age: 11.1 years) in the following situation: in 1984 and 1988 in Geneva, 1 year and 5 years after the introduction of fluoridated domestic salt (250 mg/kg), and in 1985 in Lausanne, 15 years after the general introduction of salt fluoridation for this city and its surrounding canton (Vaud). Among consumers of fluoridated salt, the average excretion of F ion during morning and afternoon was 15.4 and 43.7 micrograms F/h, respectively, in Geneva (1988) and 26.4 and 49.9 micrograms F/h, respectively, in Lausanne (1985). Among non-consumers of fluoridated domestic salt, excretion values during morning and afternoon were 9.9 and 20.7 micrograms F/h, respectively, in Geneva (1988), and 18.4 and 26.1 micrograms F/h, respectively, in Lausanne. Between 1984 and 1988, an increase in fluoride excretion was observed in schoolchildren of Geneva. During approximately 10 night hours, 8.8 to 16.4 micrograms F/h were excreted in Geneva, but F-salt consumers in Lausanne excreted 25.8 micrograms F/h. Averages of sodium excretion varied between 80 and 144 mg Na/h at daytime and between and 81 mg Na/h at night. PMID- 2928745 TI - [Fluoride retention and clearance after rinsing with fluoridated mouthwashes]. AB - Oral fluoride clearance and oral fluoride retention were studied in 12 adult volunteers. 5 different mouthrinses were used. The test agents, in part available on the market, includes two Candida mouthrinses containing 1508 and 330 ppm F, respectively, Act containing 308 ppm F, a zinc fluoride-hexetidine (ZH) combination containing 287 ppm F, and an amine fluoride 297/SnF2 (AmF/SnF2) combination containing 241 ppm F. The volunteers rinsed with 10 ml of the above solutions for 30 s each. The oral fluoride concentration was reduced to 1 ppm 99 min after rinsing with Candida original. With the AmF/SnF2 solution, the oral fluoride concentration remained above 1 ppm for 39 min, and for about 20 min after rinsing with Candida reduced, ZH and Act. With both Candida original and ZH significant fluoride levels in the oral fluid were still found after 3 h, while with AmF/SnF2 and Act significant fluoride levels lasted for 2 h. A specific clearance value was determined for each mouthrinse, reflecting the ability of the agent to remain attached to the oral structures. The AmF/SnF2-rinse had a rapid clearance value. About 9 to 17% of the fluoride brought into the oral cavity were not expectorated. For the mouthrinses containing 0.05% NaF the retention was about 0.4 mg F. This value is considered to be harmless. Mouthrinses used after the application of a monofluorophosphate-dentifrice helped to increase the relatively low oral fluid fluoride level. Rinsing with the test agents after brushing with the amine fluoride dentifrice (Elmex) produced no significantly increased fluoride levels. In-between meals eliminated the oral fluoride concentration rapidly. PMID- 2928746 TI - [The incidence of plaque and gingivitis in schoolchildren of the Davos region]. AB - The aim of the present study was to collect basic material for planning and executing a program for the prevention of caries and gingival inflammation in children. A total of 275 schoolchildren aged 8, 10 and 12 years were examined by 3 calibrated examiners in Davos Dorf and Davos Platz. The degree of plaque was measured according to the Pl-I of Silness and Loe on all permanent teeth. Gingivitis was measured using the SB-I method according to Muhlemann and Son. Oral hygiene: the eight- and ten-year-old children from Davos Dorf exhibited a significantly smaller Pl-I than their counterparts in Davos Platz. A significantly different (p less than 0.02) oral hygiene was also found between girls and boys of age 12. Gingivitis: The degree of gingivitis was minimal in the youngest age group. A significantly greater inflammation (p less than 0.03) was found in the 10-year-old group from Davos Platz. There was no discernible difference measured in the 12-year-old group between Davos Dorf and Davos Platz, but there was a distinguishable difference observed between the sexes (p less than 0.02). PMID- 2928747 TI - [Dental care after leaving school. The problem of dental care for young people after leaving obligatory school dental care]. PMID- 2928748 TI - [The DMF of children in France in 1987]. PMID- 2928749 TI - [Caries is coming again. Interview by Kurt Venner]. PMID- 2928750 TI - [Fluoridated salt: or an attempt at mass prophylaxis in France]. PMID- 2928752 TI - [Swiss agriculture at the threshold of the year 2000]. AB - The technical and biological progress together with improved educational programs for farmers have strongly influenced the development of Swiss agriculture after World War II. In spite of a decreasing number of farms and employees agricultural production has clearly increased resulting in some market problems as well as in a higher impact on the environment. Therefore, the goal of agricultural politics is to unify the sometimes divergent interests by means of offer regulation, income guarantee and environmental protection. In order to successfully meet the requirements of the 21st century, Swiss agriculture needs responsible and dynamic farmers. PMID- 2928751 TI - [What is your diagnosis? Which course of action do you propose?]. PMID- 2928753 TI - ["Infectious necrotizing hepatitis" of rabbits--the first cases in Switzerland]. AB - Based on clinical, macroscopic and light microscopical examinations we describe for the first time in Switzerland the "infectious necrotizing hepatitis" of rabbits (Marcato et al., 1988). PMID- 2928754 TI - [A retrospective clinical study of the fractures and luxations of the mandible in the cat]. AB - Twenty-six cases of mandibular fractures and luxations are reviewed. Mandibular trauma was due to car accidents (46%) and falls from great heights (23%). Cardiovascular shocks (40%), thoracic injuries (23%), epistaxis (30%), cleft palates (19%), subconjunctival hemorrhages (15%), broken canines (15%), concussions (15%), maxillary fractures (12%) were the most frequently encountered associated problems. Of the 26 cats, 22 had symphyseal fractures, 6 mandibular body fractures, 4 ramus fractures (3 of which were articular) and 6 had temporo mandibular luxations. Open reduction and internal fixation was performed in 21 cases, surgery being indicated for unstable symphyseal and body fractures, the rostral body fractures being the most challenging to repair. Conservative therapy and ancillary treatment methods such as external coaptation and pharyngostomy were used for the fractures of the ramus. Six temporo-mandibular luxations associated with mandibular fractures in 5 cases were reduced under anesthesia. Good dental occlusion and mandibular function was obtained in the 24 treated cases. PMID- 2928755 TI - Carprofen in veterinary medicine. I. Plasma disposition, milk excretion and tolerance in milk-producing cows. AB - Carprofen, a non-steroidal anti-inflammatory drug (NSAID), was injected intravenously in six cows after calving, either as a single or a daily dose of 0.7 mg/kg for five days. Carprofen was well tolerated by the cows at this dose rate, the milk production and biochemical variables remaining within the normal ranges. The plasma elimination half-life of carprofen ranged from 44.5 to 64.6 h after repeated daily injections. These values are longer than those reported for other NSAIDs used in veterinary medicine, e.g. flunixin and phenylbutazone. The volume of distribution and the clearance values calculated after a single intravenous injection amounted to 0.09 l/kg and 9.0 ml/min. The concentration of carprofen in milk collected twice daily (morning and evening) was, in general, below the sensitivity limit of the analytical method (25 ng/ml) up to five days after the last carprofen injection; the concentration of carprofen reached about 30 ng/ml in only a few milk samples collected after the fourth or fifth injection. This indicates that carprofen is poorly excreted in the milk. PMID- 2928756 TI - To our health. PMID- 2928757 TI - Time bomb. PMID- 2928758 TI - The blood-brain barrier. PMID- 2928759 TI - The syphilized world. PMID- 2928761 TI - Plasticity in brain development. PMID- 2928760 TI - Lukewarm turkey. PMID- 2928762 TI - Children of the Garden Island. PMID- 2928763 TI - Fraud in science: causes and remedies. PMID- 2928764 TI - AIDS counts. Planning for an epidemic whose size is still unknown. PMID- 2928765 TI - Virus de resistance. Drug-resistant viruses surface in AIDS patients. PMID- 2928766 TI - Multiple choice. Viral fingerprints are found in the blood of MS patients. PMID- 2928767 TI - An alliance for progress? European technology companies hope for a boost from 1992. PMID- 2928769 TI - Allium micronucleus (MNC) assay to assess bioavailability, bioconcentration and genotoxicity of mercury from solid waste deposits of a chloralkali plant, and antagonism of L-cysteine. AB - Samples of solid waste from a chloralkali plant were bioassayed employing the Allium micronucleus (MNC) assay. The endpoints measured were root length, root mercury and frequency of root meristematic cells with MNC. Chemical extraction methods such as 10% HNO3, ammonium acetate-EDTA and 0.05 or 0.1 M CaCl2 were used to assess the bioavailability of mercury from soil contaminated with solid waste. Analysis of mercury was by cold vapour atomic absorption spectrophotometry. The frequency of MNC induced by contaminated soil, which followed a concentration response curve, was statistically correlated with soil mercury, extractable mercury and root mercury. The antagonism of L-cysteine against the suppression of root growth and induction of MNC by solid waste suggested the involvement of mercury as well as thiol groups in the process. The threshold assessment values, such as the median effective concentration (EC50) for root growth, gross toxicity concentration tested (GTCT) as indicated by complete inhibition of sprouting of roots, lowest effective concentration tested (LECT) and highest ineffective concentration tested (HICT) for induction of MNC, were determined. These assessment values may be useful for environmental management and regulatory purposes. Furthermore, the detection limit of the Allium MNC assay for solid waste mercury as indicated by LECT was 9.6 mg kg-1 which corresponded to 0.13 mg kg-1 of 0.05 M CaCl2 extractable or 8.3 mg kg-1 dry weight bioconcentrated mercury. PMID- 2928768 TI - The burden of proof. Donated blood runs a costly gauntlet of tests. PMID- 2928770 TI - Polynuclear aromatic hydrocarbon content of particulate matter suspended in the atmosphere of La Plata, Argentina. AB - Twelve polynuclear aromatic hydrocarbons (PAH) were evaluated by chromatographic procedures using a HPLC-UV detector and a GC-FID detector. The PAH were evaluated in airborne particulate matter collected in La Plata, Argentina, over a period of 2 years (with sampling periods of approximately 4 months). The samples were size fractionated, and the PAH in each fraction determined. The analytical procedure used was as follows: extraction in benzene, concentration at room temperature, clean-up in a silica gel column and, finally, evaluation by chromatographic procedures. The extraction recovery was 76.2 +/- 5.8% for naphthalene and 96.0 +/ 6.2% for chrysene. Clean-up recovery was 87.8 +/- 7.15% for phenanthrene and 98.1 +/- 8.3% for anthracene. The largest PAH load was present in the smallest fractions. The smallest particles were carbonaceous in nature. The concentration peak was associated both with the total mass of airborne particulate matter and the reduction in amounts of coarse particles. The PAH distribution could not be correlated with characteristic physicochemical properties such as water solubility or the octanol-water distribution coefficient. The PAH load was greater in fall and winter than in spring and summer. This could be attributed to the reduction of photochemical processes during the cold seasons. PMID- 2928772 TI - Levels of manganese in the urine of female farmers in non-polluted regions in Japan. AB - Nearly 1500 urine samples were collected from female farmers in eight regions widely scattered in the islands of Japan in the winter of 1987-1988. The samples were analysed for manganese by wet ashing and flameless atomic absorption spectrophotometry under strict quality control. The values observed after adjustment for a specific gravity of 1.016 were distributed log-normally with a geometric mean of 0.65 microgram/l and a geometric standard deviation of 2.47. There was no effect of aging or any effect of smoking on the urinary manganese concentration. The inter-regional difference may be present but not yet conclusive. As no sex difference was observed in a previous study, it may be possible to deduce that the value may possibly stand for the "background" level of both men and women, either smoking or non-smoking, among the general Japanese population. The observed value is discussed in comparison with values reported in the literature. PMID- 2928771 TI - Accumulation of arsenic in yelloweye mullet (Aldrichetta forsteri) following oral administration of organoarsenic compounds and arsenate. AB - Groups of yelloweye mullet (Aldrichetta forsteri) were maintained for several weeks on diets containing one of a range of organoarsenic compounds (arsenobetaine, arsenocholine, 2-dimethylarsinylethanol, 2-dimethylarsinylacetic acid, 2-dimethylarsinothioylethanol) or arsenate. Fish fed 2 dimethylarsinylethanol, 2-dimethylarsinylacetic acid or 2 dimethylarsinothioylethanol showed no increase in arsenic concentrations in their muscle tissue, while fish fed arsenate showed small increases. The two groups of fish which received either arsenobetaine or arsenocholine had greatly elevated arsenic concentrations in their muscle tissue resulting from an estimated approximately 40% retention of ingested arsenic. Examination of the form of arsenic accumulated by fish fed arsenocholine showed that most of the arsenic (89%) was accumulated as arsenobetaine. PMID- 2928773 TI - Cardiac chaos. PMID- 2928774 TI - PNAS reviewing procedures. PMID- 2928775 TI - Animal activism. PMID- 2928776 TI - Alar: the numbers game. PMID- 2928777 TI - MCAT to stress thinking, writing. PMID- 2928778 TI - Unesco seeks role in genome projects. PMID- 2928779 TI - Generalized tube model of biased reptation for gel electrophoresis of DNA. AB - A theoretical analysis of the reptational motion of DNA in a gel that includes the effects of molecular fluctuations has been used to explain the main features found in experiments involving periodic inversion of the electric field. The resonance-like decrease of the electrophoretic mobility as a function of pulse duration is related to transient "undershoots" in the orientation of the molecule, in agreement with recent experimental data. These features arise from a delicate interplay of internal and center of mass motion of the molecules under pulsed field conditions, and are important for the separation of DNA molecules in the size range 0.2 to 10 million base pairs. PMID- 2928780 TI - Reduction of intestinal carcinogen absorption by carcinogen-specific secretory immunity. AB - A secretory immune response to the carcinogen 2-acetylaminofluorene (AAF) was elicited in rabbits by directly immunizing the small intestine with an AAF cholera toxin conjugate. High-titer, high-affinity secretory immunoglobulin A (IgA) antibody to AAF was secreted into the intestinal lumen in response to this immunogen. Immune secretions reduced the transepithelial absorption of a 125I labeled derivative of AAF by more than half. This reduction of absorption by hapten-specific IgA suggests that oral vaccines against carcinogens and toxicants could be developed for humans. PMID- 2928781 TI - The EGF receptor kinase substrate p35 in the floor plate of the embryonic rat CNS. AB - P35 is a calcium- and phospholipid-binding protein that was originally isolated as a substrate for the epidermal growth factor (EGF) receptor tyrosine kinase and later was found to be related to lipocortin I. Immunohistochemistry was used to localize p35 to a raphe of primitive glial ependymal cells in the median one third of the floor plate in the central nervous system (CNS) of rat embryos. The p35 appears by embryonic day 12 before the arrival of pioneering ventral commissural axons. The unexpected, discrete distribution of this protein during development opens the question of its role in neural morphogenesis. PMID- 2928782 TI - Binocular unmasking: an analog to binaural unmasking? AB - A visual analog to binaural unmasking was explored. The observer's task was to detect, under stereoscopic viewing conditions, an apertured sinusoidal grating added to a square patch of visual noise. In the experimental condition, the square patch of noise was presented within a frame such that the right-eye noise was a shifted version of the left-eye noise. Because of the disparity in the noise images, subjects perceived, under stereoscopic viewing conditions, that the noise patch was located behind the frame. When sinusoidal signals were added to this noise patch, the signals were clearly more detectable when the signal disparity was zero than when the signal disparity equaled that of the noise patch, demonstrating the existence of visual unmasking. Hence, under appropriate circumstances, binocular processing, in addition to providing information about depth, can also enhance the detectability of visual patterns. PMID- 2928783 TI - Amyloid beta protein enhances the survival of hippocampal neurons in vitro. AB - The beta-amyloid protein is progressively deposited in Alzheimer's disease as vascular amyloid and as the amyloid cores of neuritic plaques. Contrary to its metabolically inert appearance, this peptide may have biological activity. To evaluate this possibility, a peptide ligand homologous to the first 28 residues of the beta-amyloid protein (beta 1-28) was tested in cultures of hippocampal pyramidal neurons for neurotrophic or neurotoxic effects. The beta 1-28 appeared to have neurotrophic activity because it enhanced neuronal survival under the culture conditions examined. This finding may help elucidate the sequence of events leading to plaque formation and neuronal damage in Alzheimer's disease. PMID- 2928785 TI - Vitamin C papers. PMID- 2928784 TI - Prevention of rapid intracellular degradation of ODC by a carboxyl-terminal truncation. AB - Ornithine decarboxylase (ODC) was converted from a protein with a short intracellular half-life in mammalian cells to a stable protein by truncating 37 residues at its carboxyl terminus. Cells expressing wild-type protein lost ODC activity with a half-life of approximately 1 hour. Cells expressing the truncated protein, however, retained full activity for at least 4 hours. Pulse-chase experiments in which immunoprecipitation and gel electrophoresis were used confirmed the stabilizing effect of the truncation. Thus, a carboxyl-terminal domain is responsible for the rapid intracellular degradation of murine ODC. PMID- 2928786 TI - La difference. PMID- 2928788 TI - Psychiatrists examine Soviet system. PMID- 2928787 TI - Fraud review may be taken from NIH. PMID- 2928789 TI - European genome program delayed? PMID- 2928790 TI - Limits to DNA fingerprinting. PMID- 2928791 TI - Drug-resistant strains of AIDS virus found. PMID- 2928792 TI - Is risk assessment conservative? PMID- 2928793 TI - New equipment roundup dazzles scientists. PMID- 2928794 TI - Imaging crystals, polymers, and processes in water with the atomic force microscope. AB - The atomic force microscope (AFM) can be used to image the surface of both conductors and nonconductors even if they are covered with water or aqueous solutions. An AFM was used that combines microfabricated cantilevers with a previously described optical lever system to monitor deflection. Images of mica demonstrate that atomic resolution is possible on rigid materials, thus opening the possibility of atomic-scale corrosion experiments on nonconductors. Images of polyalanine, an amino acid polymer, show the potential of the AFM for revealing the structure of molecules important in biology and medicine. Finally, a series of ten images of the polymerization of fibrin, the basic component of blood clots, illustrate the potential of the AFM for revealing subtle details of biological processes as they occur in real time. PMID- 2928795 TI - Major enhancement of the affinity of an enzyme for a transition-state analog by a single hydroxyl group. AB - The compound 1,6-dihydropurine ribonucleoside, prepared by reduction of nebularine in the presence of ultraviolet light, is bound by adenosine deaminase approximately 10(8)-fold less tightly than 6-hydroxy-1,6-dihydropurine ribonucleoside, a nearly ideal transition-state analog. This difference in affinities, which is associated with the presence of a single hydroxyl group in the second compound, suggests the degree to which one or a few hydrogen bonds may stabilize the transition state in an enzyme reaction of this type. PMID- 2928796 TI - Direct measurements of sliding between outer doublet microtubules in swimming sperm flagella. AB - The relative motion of 40-nanometer gold beads bound to the exposed outer doublet microtubules of demembranated sea urchin sperm flagella has been observed and photographed during adenosine triphosphate (ATP)-reactivated swimming. This direct demonstration and measure of sliding displacements between outer doublet microtubules in actively bending flagella verifies the original sliding microtubule model for ciliary bending that was established by electron microscopy of fixed cilia and provides a new, functional measure for the diameter of the flagellar axoneme of 132 +/- 8 nanometers. PMID- 2928797 TI - Histamine is an intracellular messenger mediating platelet aggregation. AB - Inhibition of human platelet aggregation by N,N-diethyl-2-[4 (phenylmethyl)phenoxy]ethanamine-HCl (DPPE), a novel antagonist of histamine binding, suggested that histamine might serve a critical role in cell function. Phorbol-12-myristate-13-acetate (PMA) or collagen was found to increase platelet histamine content in parallel with promotion of aggregation. Inhibitors of histidine decarboxylase (HDC) suppressed both aggregation and the elevation of histamine content, whereas DPPE inhibited aggregation only. In saponin permeabilized platelets, added histamine reversed the inhibition by DPPE or HDC inhibitors on aggregation induced by PMA or collagen. The results indicate a role for histamine as an intracellular messenger, which in platelets promotes aggregation. PMID- 2928798 TI - Genes and tongues. PMID- 2928799 TI - Consensus elusive on Japan's genome plans. PMID- 2928801 TI - Science in court. PMID- 2928800 TI - Britain launches genome program. PMID- 2928802 TI - Species questions in modern human origins. PMID- 2928804 TI - Idarubicin: a new presence in leukemias. Satellite symposium. Milan, August 1988. Proceedings. PMID- 2928803 TI - Scanning tunneling microscopy of uncoated recA-DNA complexes. AB - Uncoated recA-DNA complexes were imaged with the scanning tunneling microscope (STM). The images, which reveal the right-handed helical structure of the complexes with subunits clearly resolved, are comparable in quality to STM images of metal-coated specimens. Possible conduction mechanisms that allow STM imaging of biological macromolecules are discussed. PMID- 2928805 TI - Idarubicin in acute leukemias: experience of the Italian Cooperative Group GIMEMA. PMID- 2928806 TI - Idarubicin plus cytarabine as first-line treatment of acute nonlymphoblastic leukemia. PMID- 2928807 TI - A multicenter trial of cytarabine plus idarubicin or daunorubicin as induction therapy for adult nonlymphocytic leukemia. PMID- 2928809 TI - Hepatic imaging. PMID- 2928808 TI - Idarubicin in acute leukemia: results of studies at Memorial Sloan-Kettering Cancer Center. PMID- 2928810 TI - The measurement of hospital efficiency: a comment. PMID- 2928811 TI - Effects of breast cancer and mastectomy on emotional support and adjustment. AB - Wortman and Dunkel-Schetter (J. Soc. Issues 35, 120-155, 1979) have argued that victims of misfortune are likely to experience reduced social support at a time when support is needed most. The resulting self-doubt and isolation are thought to increase the victims' distress. Hypotheses derived from their analysis were tested by administering social and emotional adjustment inventories to 301 women who had undergone a mastectomy as treatment for breast cancer, and to 100 women diagnosed as having benign breast lumps (no-cancer, no-mastectomy controls). As expected, perceived emotional support was positively correlated with adjustment. However, contrary to Wortman and Dunkel-Schetter's analysis, the cancer patients perceived greater emotional support from friends and family than did the controls. In addition, these cancer 'victims' were no more socially or emotionally maladjusted than women without cancer. PMID- 2928812 TI - Dimensions of negative affectivity, self-reported somatic symptoms, and health related behaviors. AB - This study focused on the relationship between personality dispositions, self reported somatic symptoms, and health-related behaviors in undergraduate students. Findings are presented which indicate systematic correlations between health complaints and negative affectivity (NA), a common and pervasive mood disposition. Generally, there was a stronger relationship between NA and self reported somatic symptoms than between NA and variables reflecting health-related behaviors, lifestyle, and general fitness. Significant correlations between health complaints and capacity for imaginative involvement (absorption), as well as self-reported measures of emotional inhibition, were also demonstrated. However, it is uncertain whether absorption and emotional inhibition properly belong to the NA construct. The results also indicated differences with respect to the strength of the associations between various dimensions of NA and particular types or classes of health complaints. For example, cognitive anxiety (e.g. worry, ruminations, disturbing thoughts) was more strongly related to somatic complaints than behavioral (social avoidance) components of anxiety. Moreover, diffuse and widespread symptoms (e.g. weakness and fatigue) were more strongly associated with NA than more specific and localized symptoms, particularly musculo-skeletal complaints, although complaints belonging to the musculoskeletal category obtained the highest group mean score. The results strongly suggest that a differentiated approach to the study of NA-symptom connections should be adopted. PMID- 2928813 TI - Defensive work in nursing homes: accountability gone amok. AB - This paper contrasts conditions in intensive care nurseries and skilled nursing facilities in order to bring out certain features of organizational functioning in nursing homes. Data stem from a study of three American nursing homes which focused on the circumstances influencing decision-making in the evaluation and treatment of acute illness. DEFENSIVE WORK--work that is institution-protective and/or self-protective-emerged as a dominant process. It is demonstrated that the avoidance strategies which constitute defensive work lead to a progression of counterstrategies and foster skewed priorities. Consequences are: an acceptance of substandard care and a diversion of attention from therapeutic work. The relationship of defensive work to the larger question of how the nation handles its sick elderly is examined in the conclusion of the paper. Recommendations are offered for organizational steps that would re-channel the wasted energy that is spent on defensive work toward more productive therapeutic work. PMID- 2928814 TI - Measuring satisfaction with health care: a comparison of single with paired rating strategies. AB - One of the central problems in studies of patient satisfaction with health care is the development of reliable and valid methods to determine the relative importance of different aspects of health care. Two techniques, paired comparisons and rating on a visual analogue scale, were compared in terms of their consistency with logical assumptions, test-retest reliability, and convergent validity. Thirty women with breast cancer were asked to assess brief hypothetical scenarios describing out-patient clinic visits to a tertiary cancer care centre. Each scenario incorporated three variables related to satisfaction with care: staff attitude, control over treatment decisions, and continuity of medical supervision. The paired choice method showed marginally better reliability and logical consistency than the rating method. Of the three variables assessed, continuity of medical supervision was consistently ranked highest in importance, and control over treatment decisions lowest. These preference assessment techniques appear to be suitable for use in the development of patient satisfaction indices, and for studies designed to examine variations in the priority given to different aspects of satisfaction with care. PMID- 2928815 TI - A prospective study to identify the fall-prone patient. AB - A prospective study in 16 patient care units in two institutions was conducted to assess patients' risk of falling. Three types of patient care units were utilized (acute medical and surgical, long term geriatric and rehabilitation areas), with 2689 patients over a 4-month period rated daily for fall risk using the Morse Fall Scale. Differences in mean fall score were evident between the acute care areas and the long term and the rehabilitation areas. Examination of the scores in the acute care institution by length of stay, showed different patterns of fall risk; the mean score of the long term patients showed less variation and higher scores. Patients' falls were analyzed by fall score and type of fall. All types of falls (anticipated physiological, unanticipated physiological and accidental), and the severity of injuries increased, with increasing scores indicating clinical validity of the scale. PMID- 2928816 TI - It's how you say it: physicians' vocal behavior. AB - The present study was designed to assess evaluations of physicians interacting with patients via the telephone. Observers used ten adjective scales which resulted in three variables: empathic, dominant, and calm. Thirty doctor-patient interactions were presented in two different communication modes: audio-only and typed transcript-only. As predicted, female listeners rated doctors as more empathic, dominant, and calm, and communication modes were significantly different with audio segments rated as more empathic, dominant and calm. Middle phases of the conversation also were evaluated more positively than greeting phases. Significant interactions between temporal phase and mode indicated that audio segments were interpreted more positively during middle phases. Also, female listeners were more sensitive to audio segments. Physicians' amplitude and speech rate were positively correlated with dominance. PMID- 2928817 TI - Health information imperatives for Third World countries. AB - The role of health information in the health delivery services of a nation is stressed with examples from the advanced nations. Factors responsible for the poor state of health information systems in the Third World and the effects on health delivery services are identified. probable factors that may Lead to the development of health information systems in the Third World in the future are posited. Recommendations for the establishment of health information systems based on funding, staffing, functions and networking are made. PMID- 2928819 TI - Using administrative data from Manitoba, Canada to study treatment outcomes: developing control groups and adjusting for case severity. AB - Administrative data are becoming increasingly available to health care researchers across North America and Europe. Such data sources are generally thought to be useful for documenting health care utilization. In this report, data from the provincial health insurance system in Manitoba, Canada are used to develop control groups and adjust for case severity. These are necessary prerequisites for using administrative data to study health care outcomes. PMID- 2928818 TI - Three conflicts as a result of causal attributions. AB - There is a difference between the causal attributions of cancer (Ca)-patients and those of myocardial infarction (MI)-patients. MI-patients go through and check their autobiographies looking for the possible causes suggested by the medical world. Ca-patients on the contrary search for possible explanations. This is probably due to the lack of medical knowledge on the cause and course of their disease. They search through their autobiographies and the result is idiosyncratic, very personal attributions with which they create an explanation which is often not in accordance with the physicians' view. These attributions of Ca-patients are a source of conflicts, both within themselves (doubt), with their physicians and with their partners or other close relatives. Nevertheless they stick to their own explanations, although often secretly and with ambivalence, and despite the conflicts which they produce. PMID- 2928820 TI - Coronary arteriography rates in Switzerland--how do they vary? AB - Coronary heart disease is a leading cause of death for both sexes in developed countries. Controversy has arisen about the health benefits and risks of coronary surgery and, more recently of coronary angioplasty. As a clinical prerequisite to these interventions, coronary arteriography can be considered an indicator of invasive services offered to coronary heart disease patients. We collected data on characteristics of all patients subjected to coronary arteriography during 1984 in Switzerland. A total of 4921 coronary arteriographies were performed among 4359 patients; this corresponds to 77 procedures/100,000 residents and 68 patients/100,000 residents. Rates for men are 4.2 times women's rates, and the highest utilization rate for both sexes are observed in the group aged 40-64. Large variations characterize cantonal and regional coronary arteriography rates. Similarly, the distribution of centers practising this procedure is not uniform. These observations are placed in the context of the general practice of coronary angiography, changes expected in the face of by-pass surgery and angioplasty expansion, and coronary heart disease data. PMID- 2928821 TI - Regional dispersion of independent professionals in primary health care in The Netherlands. AB - One of the main objectives of Dutch Government policy on primary health care concerns equal regional dispersion of health care provisions. At this moment these provisions are geographically not equally distributed when measured in terms of the number of inhabitants per practising professional in primary health care. In this paper the current patterns of dispersion of five professional groups are described. The groups concerned are the general practitioners, dentists, physiotherapists, pharmacists and midwives. These patterns are mainly a consequence of market forces because the professionals have had the freedom to choose where to practise their profession until recently. These decisions are affected by the "place utility" of an area. In this paper place utility is conceived as being determinated by the opportunities of an area to earn a living and the amenities of an area as residential and living-environment. These concepts are operationalized by a set of independent variables. In order to understand the (differences between the) patterns of dispersion of the professional groups concerned multiple regression-analysis has been used, of which the results are compared to the hypotheses formulated. PMID- 2928823 TI - A cartographic study of hospital utilization in the county of Uppsala. AB - In this study the question whether increased resources in community based primary care lead to decreased utilization of in-patient care has been analysed. Two alternative types of analysis were compared: a municipality-based analysis and a cartographic analysis based on non-administrative reference areas. The study material consisted of person-based data from Uppsala County in Sweden. The cartographic analyses revealed important characteristics of the utilization pattern, which would not have been possible to ascertain using traditional methods such as analyses based on administrative areas. Thus, the cartographic analysis gave some support to the hypothesis that increased resources to primary care will reduce the utilization of in-patient care. PMID- 2928822 TI - An investigation of the effect of regional variation in the treatment of hypertension. AB - Over a period both a monetary and physical measure of antihypertensive drug consumption has increased in Denmark, but the consumption has varied considerably between counties in any given year. Concurrently, SMR for myocardial infarctions and cerebrovascular diseases due to hypertension has declined. The relation between intensity of treatment and outcome in terms of reduced loss of life time or healthy time is analyzed at an aggregate level within a health economic framework. The relation is analyzed by using a pooled time series cross section regression analysis. Two models, a covariance and an error component model are used. Within the range of observed drug consumption, loss of life years and loss of good health show a tendency towards negative regression on consumption of drugs when controlled for relevant variables such as occupational structure, degree of urbanization, and hardness of the drinking water. PMID- 2928824 TI - A quasi-experimental design based on regional variations: discussion of a method for evaluating outcomes of medical practice. AB - A large proportion of common medical practices are subject to substantial regional variation resulting in numerous natural experiments. Opportunities are thereby provided for outcome evaluation through quasi-experimental design. If patients treated in different regions were comparable a natural experiment involving alternative treatments could be regarded as 'pseudo randomised', but empirical investigations are needed to verify this prerequisite. This paper discusses the role of quasi-experimental designs in assessment of medical care with evaluation of outcomes after hysterectomy in Denmark as an example. The design is developed and the comparability of selected groups of patients is elucidated from administrative data, while the outcome results are not presented in this context. One indication for hysterectomy is carcinoma in situ of the cervix uteri which may be treated with either hysterectomy, or conisation. A study group of patients was selected from departments where hysterectomy was the treatment of choice for this indication while the reference group was drawn from departments in which conisation was generally preferred. The comparability of the populations, effects and information for the two groups are elicited from administrative data. We conclude that it is possible to establish a quasi experimental design based on regional variations and that the comparability of the groups included may be assessed through registry data. The importance of technology diffusion for the prospects of performing quasi randomised studies is emphasised. In this attempt to evaluate hysterectomy, it was not possible to identify groups of patients, which were sufficiently comparable to justify a study of soft outcomes. PMID- 2928825 TI - "A built bed is a filled bed?" An empirical re-examination. AB - This article provides an empirical re-examination of the relationship between regional hospital bed supply and the utilization of hospital care. It tests the hypothesis that the divergence of findings between studies based on micro-data (at the individual level) and those based on macro-data (at the regional level) is due to aggregation and specification bias. The main conclusion is that neither source of bias can account for the observed differences. Some other possible explanations are put forward. Regardless of the level of aggregation, a positive effect is found of bed supply on length of hospital stay but not on admission rates. This may be the result of major changes which have taken place in the financing of hospital services in the Netherlands during the last decade. PMID- 2928826 TI - Variations in resource utilization--the role of medical practice and its economic impact. AB - Several studies have indicated that differences in medical practice are often an important factor behind variations in resource utilization. 'Practice', in medical contexts, is used as a comprehensive expression for what is regarded to be adequate care, considering science and proven experience, as well as present resources, demography, organization, and other given conditions. However, experience shows that routines and practice, even under similar conditions (resources, organization, etc.) often vary significantly among departments within the same medical discipline. In this more restricted sense, variations in practice might depend on different--more or less well-founded--opinions among physicians concerning what constitutes appropriate length of stay, level of care, and technology. With examples from some specialties (e.g. general surgery, obstetrics and gynecology), we demonstrate this 'model' and the economic impact of practice variations. Our conclusion is that there are opportunities for achieving greater benefit from existing resources, i.e. increasing efficiency, through reallocation and alternative utilization of resources, altered practice. PMID- 2928827 TI - Assessing data quality: a computerized approach. AB - With the growing reliance on large health care data bases, the need to verify data quality increases as well. Because of the considerable costs involved in checks using primary data collection, a computerized methodology for performing such checks is suggested. The technique seems appropriate for any situation where two data collection systems (i.e. hospital discharge abstracts and physician claims for payment) relate to the same event, such as a patient's hospitalization. After reviewing other approaches, this paper suggests linking physician claims for performing particular surgical procedures with hospital discharge abstracts for the stay in which the surgery took place. Physician and hospital data for adults age 25 and over in Manitoba from 1 April, 1979 to 31 March, 1984 were used to address the questions: 1. How well can the two data sets be linked? 2. Given linkage of the two data sets, how much agreement is there as to procedure and diagnosis? Linkage between hospital and physician data was excellent (over 95%) for 5 out of 11 surgical procedures (hysterectomy, prostatectomy, total hip replacement, coronary artery bypass surgery, and heart valve replacement); there was over 90% perfect agreement for three other procedures (cholecystectomy, cataract surgery and total knee replacement). Problems with matching the Manitoba Health Services Commission tariffs (on physician claims) with ICD-9-CM operation codes (on hospital data) led to only 77% perfect agreement for vascular surgery and 84% for gallbladder and biliary tract operations other than cholecystectomy; over 10% of the cases linked on surgeon and date but not on the designated procedures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2928829 TI - Geographic variation on health care use. PMID- 2928828 TI - Professional uncertainty and physician medical decision-making in a multiple treatment framework. AB - This paper develops a new microanalytic approach to physician medical decision making treatment setting. Physician medical decision-making is modelled as a two stage sequential process. In Stage 1, the patient's illness is diagnosed and the health outcomes for all illness-related restoration options are identified. In Stage 2, an "optimal" restoration option is selected. This model provides new insights into physician medical decision-making and the complexity of proving physician-induced demand in a medical care market where professional uncertainty and consumer heterogeneity exist. PMID- 2928830 TI - The political economy of health and disease in Africa and Latin America. Papers from a research planning workshop. Toluca, Mexico, January 1985. PMID- 2928831 TI - [The state, social class and health]. AB - This paper analyses the health policies implemented in Argentina during the last four decades, relating their application to concomitant development strategies that were underwritten by political projects advancing different 'societal models'. Our hypothesis is that, in Argentina over the last four decades, there have been three major attempts at adjusting the internal needs of capitalist development to the conditions imposed by the world capitalist system. Such strategies, globally termed 'populist', 'developmentalist' and 'authoritarian', imply a modification of the relationships between state and economy (mode of development) and between state and society (mode of hegemony). They also involve peculiar ways of approaching the contradiction between accumulation and distribution, and consequently, different methods for solving social problems and alternative paths to the consolidation of a hegemonic project. Within this context, both the rationale offered by the state for its proposed health and welfare policies, as well as the actual implementation of these policies conforms to the basic principles of each of the models in force. In the populist model, the political project involves a progressive expansion of the participation of the popular sectors, both in the labour and consumption markets and in the political system. Its health plan conforms with this model by recognizing the state's responsibility both to increase its participation in health services and to promote corporativist activities in the sector, in accordance with the global mobilization/incorporation policy controlled by the mass organizations. In the developmentalist model, emphasis falls on the need to privilege accumulation over distribution; investments in infrastructure are treated as a priority as they are considered indispensable to ensure the future generalization of public welfare. The argument is that the impact of medical assistance on labour productivity must go hand in hand with the creation of job opportunities from economic development. Finally, the authoritarian model excludes the promotion of concensus politics in an effort to radically transform the articulations between state and society. The disciplinary function of the market is used to concealing both a serious lack of interest in the population's living conditions and an iron decision to subject the totality of social life to the rationality of a system where social injustice stands as the society's bastion. PMID- 2928832 TI - The fruits of empire rot on the vine: United States health policy in the austerity era. AB - Since 1970--with the decline in the hegemonic empire--the U.S. economy has entered a period of lower profitability, producing a major shift in the economic behavior of corporate capital. In contrast to the demand stimulation (New Deal) programs of the earlier period of prosperity capitalism, capital has moved toward a profit stimulation strategy in the current era of austerity capitalism. Fundamental to this austerity strategy is the drive to reduce costs of production. Both governmental and employee health benefits represent a cost of production. Thus in the health field, austerity strategy signifies a reduction in the provision of health benefits to employees and cuts in governmental health programs. An effect of austerity capitalism may be that health patterns now mainly confined to the underdeveloped world will become more prominent among the low-wage and unemployed sectors of the working class in the United States. PMID- 2928833 TI - Factors distinguishing homosexual males practicing risky and safer sex. AB - A longitudinal study of patterns of sexual behavior among asymptomatic, homosexual males in New York City was conducted. Participants were interviewed at two time points, 6 months apart. Based on their reports of sexual behavior during a recent 'typical' month, respondents were classified at each time point as engaging in safer (or low-risk) sexual practices versus high-risk sexual behaviors. Discriminant analysis was employed to distinguish the 53 males classified as risky at both time 1 and time 2 from the 47 males classified as safer in both periods. Statistically significant discrimination was achieved with 10 psychosocial predictor variables, four of which were significant while controlling for all other variables in the model. Of these predictors, drug use within sexual contexts was particularly noteworthy, since it provided the greatest relative contribution to the discriminant function and appears to be an important candidate for educational intervention. Other significant variables included perceived adequacy of emotional support, number of years engaged in regular sexual intercourse with other males, and perceived difficulty in modifying sexual behavior. Self-esteem and alcohol consumption approached significance. PMID- 2928834 TI - An evaluation of the psychological and social effects of malocclusion: some implications for dental policy making. AB - Initial findings are reported from a longitudinal study investigating the effects of malocclusion on dental health and psychological well-being and the effectiveness of orthodontic treatment. Implicit in the orthodontic intervention decision process is the view that there are discernible social and psychological benefits of good occlusion. This view has not been adequately validated. The primary psychological question addressed by this study concerns the relationship between adolescents' orthodontic status and their psychological status and well being. Empirical evidence allowed an examination of the major hypothesis that children with poor occlusion are likely to be socially and psychologically disadvantaged. Ratings of dental status and physical attractiveness, and measures of psychosocial well-being were obtained for sample of 1018, 11-12-year-old children and the associations between these variables were examined. The results provide little support for the major hypothesis that children 'suffer' psychologically from having poor dentition. Several points of caution are made with regard to this conclusion and some implications for dental policy making are considered. PMID- 2928835 TI - Diarrhoeal diseases: perceptions and practices in Nepal. AB - A study undertaken in Nepal collected information on believed causes of diarrhoea and traditional treatments. Natural causes for diarrhoea were more frequently reported than supernatural causes, the most important being teething (75% of respondents reporting it to be a cause) followed by food considered to be 'cold' in the Hindu ayurvedic classification (57.5%), stale food (52.5%), hot food (41%) and dirty water (38%). The terminology reported for dehydration however, indicates strong links with supernatural causes. For prevention of diarrhoea the recognition of the importance of stale food and dirty water is encouraging for health education programmes. Its association with teething may be an obstacle. In the promotion of correct diarrhoea management, the high proportion (83%) of mothers reportedly continuing to breast-feed is a good sign, but 75% of respondents reported that fluids are always or sometimes withheld, and 58% that foods are withheld. The literature does suggest that administration of certain foods and fluids is the commonest form of treatment of diarrhoea, but the choice of these is based upon the hot-cold principle. Both diarrhoea and dysentery were reported to be caused by both 'hot' and 'cold' influences in this study. In addition, 'hot' and 'cold' foods and fluids were reported to be both useful and harmful in their treatment. Thus, while treatment by giving foods or fluids is suitable, neither 'hot' nor 'cold' types will be universally acceptable. The promotion of oral rehydration solution consequently needs to be flexibly manipulated in terms of the hot-cold principle. The current recommendation of its preparation using cold water may be unacceptable in a proportion of cases. A wide variety of nutritious foods and fluids were reported to be considered beneficial and it is concluded that these traditionally accepted feeding practices should be reinforced, especially at the onset of diarrhoea in infants and children. PMID- 2928836 TI - Healers in transition. AB - This paper, through the use of case histories illustrates the variety of traditional practitioners to be found in Plateau State Nigeria. The changes that some of them have undergone in the absence of official policy regarding integration, and under the influence of Western medicine, are discussed in terms of role adaptation. The options for collaboration between traditional and Western medicine are discussed and specific examples in Ghana, Nigeria, Senegal and Zambia are given. Potential problems facing such programmes are raised together with possible benefits. The need for a deeper understanding of traditional practitioners and their interest in co-operating with Western medical systems is discussed as well as the contribution that the use of case histories could make to this process. PMID- 2928837 TI - Social inequalities in low birth weight: timing of effects and selective mobility. AB - The risk of giving birth to a low birth weight baby is known to be associated with poor material circumstances during the mother's own childhood. In addition to this long-term effect, an association is also apparent of low birth weight with the mother's current social class, measured in terms of her husband's occupation. At least two interpretations of this are possible: a true short-term effect, and/or selective social mobility (upward or downward). According to the latter hypothesis, social class at marriage reflects the operation of selective social processes such that taller and better educated women tend to marry men of higher social class: because both attributes are negatively associated with the risk of low birth weight, a short-term effect is mimicked. This paper investigates the strength of this effect, using data from a longitudinal study, the National Child Development Study. The possibility is also explored that the social class gradients at different ages are not independent: for example that a beneficial socio-economic environment in early life can compensate for hardship later on, in terms of the risk of low birth weight, and vice versa. A social class gradient was observed in the proportion of low birth weight deliveries, both at the time of the respondent's own birth and at the time of her marriage. Depending on the assumption made concerning the relationship of height with low birth weight, selective mobility for height explained 10.7% or 16.3% of the apparent short-term gradient in low birth weight. Selective mobility for educational level did not have any effect. Further analyses suggested that having belonged to a higher social class either in early childhood or at marriage had a beneficial effect, notwithstanding the direction of any mobility experienced. The social class of the woman's father when she was 16 was not associated with the low birth weight rate, and upward mobility during the respondent's childhood appeared to carry an increased risk. PMID- 2928839 TI - Infection of bovine cells of embryonic origin by amphotropic retroviral vectors. AB - Two amphotropic-based mouse retroviral vectors carrying the neomycin-resistance gene were used to infect four bovine cell lines. Two cell lines, bovine kidney and spleen cells, were refractory to the infection while two independent bovine cells of apparent embryonic origin were infected by the amphotropic retroviral vectors at a measurable titer. Southern blot analysis reveals the presence of neomycin-resistance gene in the G418-resistant bovine cells. The results demonstrate the successful transfer of a gene to bovine cells of embryonic origin using a murine retroviral vector system. PMID- 2928838 TI - X-chromosome inactivation in cultured cells from human chorionic villi. AB - X-chromosome inactivation was investigated in human chorionic villi in the first trimester of pregnancy and cultured cells established from them. Expression of glucose-6-phosphate dehydrogenase (G6PD) was evaluated in these extraembryonic cells from four females heterozygous for the electrophoretic variants (AB) of G6PD. In each case the uncultured villi as well as derived cultured cells expressed the AB phenotype for G6PD with about equal intensity for the A and B bands. Single-cell-derived clones established from two of the four cases expressed either G6PD A or B. One clone expressing G6PD B was fused with mouse cells, and a hybrid clone retaining the inactive human X chromosome was isolated; there was no evidence of human G6PD expression in this clone retaining an inactive human X. DNA methylation in the first intron of the human gene for hypoxanthine phosphoribosyltransferase (HPRT) was evaluated in the four pairs of cultured villi and fetal cells. No differences were detected between the cultured villi and fetal cells as they all showed bands characteristic of an inactive X from somatic cells. These results show that there is no preferential inactivation of an X in the majority of cells that constitute human tertiary chorionic villi or in cultured cells derived from them. Long-term cultures established from chorionic villi appear to be no different from somatic cells with respect to X chromosome inactivation. PMID- 2928840 TI - Cloning of TPA-inducible early (TIE) genes by differential hybridization using TPA-nonresponsive variant of mouse 3T3-L1 cells. AB - The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) induces DNA synthesis in quiescent 3T3-L1 cells but not in its variant VT-1 cells. A lambda gt10 cDNA library was constructed using poly(A)+ RNA from 3T3-L1 cells that were stimulated by TPA for 20 min. Radioactive cDNA probes were prepared from mRNAs of TPA-treated 3T3-L1 and VT-1 cells and used for screening of the 3T3-L1 cDNA library by differential hybridization. Nine of 6000 phase plaques hybridized only to the 3T3-L1 cDNA probe. Analysis of the nucleotide sequence of five of these clones indicated a high degree of homology with human or mouse type I and type III collagen genes. Three other independent clones showed no homology with any known DNA sequences. These isolated clones of TPA-inducible early (TIE) genes may be useful to study the signal transduction pathway of phorbol esters. PMID- 2928841 TI - Allelic variation linked to adenine phosphoribosyltransferase locus in mouse teratocarcinoma cell line and feral-derived mouse strains. AB - Southern blot analysis reveals two distinct adenine phosphoribosyltransferase (APRT) alleles in the P-19 mouse teratocarcinoma cell line. One allele is identical to that observed in common laboratory mouse strains (Mus musculus domesticus). The restriction enzyme site variations between the two alleles occur in sequences located both upstream and downstream of the APRT gene, but not within it. Although the P-19 cell line was established from a C3H strain embryo (Mus musculus domesticus), a sixth generation ancestor of this embryo was a feral mouse (Mus musculus musculus). The restriction pattern of the variant APRT allele in P-19 is identical to that of a feral-derived Mus musculus musculus animal, establishing the origin of this allele in the P-19 cell line. A third, distinct APRT allele was found in a Mus spretus feral-derived mouse. Exploiting the differences between the two APRT alleles in the P-19 cell line, we have demonstrated their sequential loss in APRT-deficient clones. PMID- 2928842 TI - Gene on short arm of human X chromosome complements murine tsA1S9 DNA synthesis mutation. AB - We have created somatic cell hybrids between the temperature-sensitive mouse cell line tsA1S9 and human cell lines in order to localize the human gene (A1S9T) complementing the cell cycle defect of the murine line. Segregation of the human X chromosome is completely concordant with growth at the nonpermissive temperature. Hybrids retaining the X chromosome are temperature-resistant, whereas those without a human X are temperature-sensitive. Further hybrids made using human cell lines with X-autosome translocations indicate that the A1S9T gene is located on the short arm of the human X chromosome. PMID- 2928843 TI - Unique chromosomal location of amplified EGF receptor genes in EGF receptor hyperproducing tumor cell line NA. AB - The epidermal growth factor receptor (EGFR) gene was analyzed by in situ hybridization using a squamous cell carcinoma line NA, which has high numbers of EGF receptors and carries a 20-fold amplification of EGFR genes. NA cells are pseudotriploid (mode of chromosome number is 69) and have three copies of an apparently normal chromosome 7 together with several aberrant chromosomes. Strong hybridization signals were observed in the abnormal banding region of one of the aberrant chromosome, MH1, which has no structural homology to chromosome 7. This MH1 chromosome was lost in NA-derived variant lines that possess reduced numbers of EGF receptors. These results are in contrast to previous findings that EGFR gene amplification is associated with structural alterations of the short arm of chromosome 7 and provide new evidence in regard to the location of the amplified EGFR gene in tumor cells. PMID- 2928844 TI - Regional mapping of RBP4 to 10q23----q24 and RBP1 to 3q21----q22 in man. AB - The human gene coding for RBP4 has been assigned to 10q23----24 using a panel of somatic cell hybrids and in situ hybridization experiments. The mapping of the human RBP1, previously assigned by our group to chromosome 3 using a panel of somatic cell hybrids, was restricted to the region 3q21----22 using in situ experiments and Southern blots of genomic DNA from a hybrid retaining a portion of chromosome 3. PMID- 2928845 TI - [Percutaneous sclerotherapy of varicoceles using a coaxial catheter system]. PMID- 2928846 TI - [Fragmentation of large and impacted gallstones using ultrasound]. PMID- 2928847 TI - [Diagnostic criteria for recurrent lumbar intervertebral disk prolapse in myelo CT]. PMID- 2928848 TI - [Results of surgical and conservative therapy of tracheal and tracheoesophageal lesions]. AB - The paper deals with 10 years of experience a multispecialty team has reached in the therapy of tracheal stenoses and acquired tracheoesophageal fistulas. In 38 surgical patients the authors performed 50 reconstruction operations. The best results were reached in stenoses and tumours of trachea provided the patient had not died after the operation. In the group of 13 patients with surgery for tracheoesophageal fistula there were seven who died in the postoperation period. The problem of reoperation is discussed as well as the technique of the intervention with the use of Rehn's grafts and microsurgery occlusions of the fistulas by way of a tracheostoma. Two previously published cases are briefly described, the first being a complete resection of tracheal bifurcation, the other one being a rare mucosa form of epidermolysis bullosa, localized and surgically treated in the region of cervical oesophagus. PMID- 2928849 TI - [Concepts in the treatment of injuries of the thoracic and lumbar spine]. AB - The thoracolumbar connection represents a particular problem in view of the extent and stability of spine damage. A retrospective examination after conservative treatment of unstable injuries has shown unfavourable results. The authors therefore established a new therapeutic concept for this injury. Instable injuries should be surgically treated as early as possible, those with neurological defect are subject for emergency operation. A surgical approach (posterior transpedicular) is described. The urgent operation on the injured persons with medullar lesions enable an early rehabilitation and prevents further complications. PMID- 2928850 TI - [Cardiac decompression using pulmonary artery drainage during operations with extracorporeal circulation]. AB - The authors report their experience with the application of decompression of the left ventricle of the heart by means or active suction from pulmonary artery. This way of heart drainage has been so far used in 53 patients, who were operated in extracorporal circulation. The drainage of pulmonary artery proved to be completely successful. It enabled a sufficient decompression of the left heart and prevented most complications which may occur if a direct drainage of the left ventricle of the heart is applied. PMID- 2928851 TI - [The importance of local therapy of burns in infants and toddlers]. AB - The present paper summarizes 10 years of experience in the treatment of 403 burned children at the age up to three years. A local therapy constitutes an important part of the treatment and always influences the final result. The application of 1% silversulfadiazin (Dermazin) markedly decreased bacterial contamination of the burned surfaces. Tangential necrectomy interventions were performed in deep dermal burns and burns affecting the whole thickness of the skin. In the sucklings a more conservative way of surgical therapy proved successful. A long-term observation of the patients proved to be necessary. PMID- 2928852 TI - [Choledochocele diagnosed before surgery]. AB - The authors describe the case of a 73 year old man with obstruction jaundice, who was examined before the operation by PTC with resulting diagnosis of choledochocoele connected with cholelithiasis. The preoperation diagnosis of this rare anomaly is not frequent and is due to the development of radiodiagnostic methods. A surgical solution is based either on discision or removal of the whole formation. PMID- 2928853 TI - [Secondary access routes for hemodialysis]. AB - During the period of 1970-1985 375 arteriovenous fistulae were constructed in 248 dialyzed patients. The number of fistulae needed for long-term dialysis was significantly higher in women. Five-year cumulative patency rates were significantly better in the first fistulae than in the second, third or following fistulae. The best long-term patency rates were achieved in radiocephalic fistulae. Of all secondary vascular access procedures saphenous vein grafts proved to be the most reliable. PMID- 2928854 TI - [Symptomatic aneurysms of the abdominal aorta]. AB - In the years 1981-1985 21 patients were operated upon for symptomatic abdominal aortic aneurysms. Atypical symptoms such as acute pancreatitis, weight loss, blood in the stool or urine, incorrect interpretation of abdominal pain and physical examination findings caused erroneous initial diagnosis and delay in referring the patient to surgical treatment in nine cases. Long history prior to admission was noted even in patients with ruptured aneurysms; mortality in these patients was high, 66%. Best results were achieved with aneurysm resection; indirect aneurysm occlusion in combination with axillofemoral bypass attempted in two patients was not successful. PMID- 2928855 TI - [Sexual disorders after colorectal operations]. AB - After extensive colorectal operations there are sexual dysfunctions in the patients in 16-100%. In our cohort of 36 men the post-operation sexual disorders were reported in 21.3%. The authors present an anatomical survey of nerve supply of the organs influencing sexual activity emphasizing tactical and technical measures during the operations which could prevent the damage of important nervous structures. PMID- 2928857 TI - Some changes in anatomical nomenclature. PMID- 2928856 TI - [A study of the health services and needs of the elderly (SENSORG)]. AB - Our department was approached by various welfare organisations who experienced problems with the placing of the frail elderly in suitable homes. The SENCARE project was planned to ascertain the health needs of the white and coloured elderly living in old-age homes and in the community and to identify the existing health services available to them by using the questionnaire method of measurement. The study was done in 3 phases: phase I in an urban area, phase II in a large rural town and phase III in 5 small rural towns. In the urban area too many healthy white elderly people live in old-age homes. The availability of services is poorer in the rural areas. In all 3 phases social and economic impairment is the major cause of dependence in both the white and coloured elderly population groups. PMID- 2928858 TI - Some views on academic medicine in South Africa. PMID- 2928859 TI - [Is there still a future for academic medicine in South Africa? Memorandum prepared by the Academic Medical Personnel Association, Tygerberg Hospital]. PMID- 2928860 TI - Dorsal ganglion of the wrist--pathogenesis and biomechanics. Operative v. conservative treatment. AB - It is shown that the dorsal ganglion arises as a herniation from the dorsal scapholunate ligament. This herniation increases in size (according to La Place's law) owing to the unidirectional pinchcock effect of the mucosal folds of the duct and the pressure of the overlying extensor retinaculum until the distending pressure inside the ganglion equals the overlying tissue pressure. Wrist gangliography, retrograde wrist arthrography, histology and nuclear magnetic resonance were used to prove this conclusively. Bearing the pathogenesis in mind, the best clinical results were obtained by excision of the ganglion with 0.5 cm2 of dorsal scapholunate ligament and closure of the dorsal capsule with a 3/0 Vicryl purse-string suture. Non-surgical sclerotherapy led to severe inflammation and sepsis and a recurrence rate of 45%. Conservative therapy is illogical since the communicating duct remains and synovial fluid from the scapholunate joint will cause a reherniation and recurrence of the ganglion. PMID- 2928861 TI - Pregnant adolescents in rural Transkei. Age per se does not confer high-risk status. AB - No significant differences were found when the obstetric outcome of 515 rural adolescents aged 16 years and younger was compared with that of an equal number of matched young adult rural women aged 20-29 years in respect of booking status, postpartum haemoglobin content, operative/instrumental delivery, mean neonatal birth mass and the incidence of infants weighing under 2,500 g. These results support the conclusions of recent studies in Australia and the USA that adolescence per se confers no increased obstetric risk. On the other hand, unwed motherhood (among all age groups) constitutes a most disturbing social trend in black rural society and this, rather than teenage pregnancy as such, ought to be the focus of concern for social workers and the medical profession. PMID- 2928862 TI - Pituitary resistance to L-thyroxine after thyroidectomy. A case report. AB - The clinical and laboratory findings in a 29-year-old Saudi Arabian woman were compatible with a state of resistance to thyroid hormones by the pituitary gland. Symptoms of hypothyroidism, amenorrhoea and secondary infertility developed 10 years after partial thyroidectomy for an euthyroid goitre. Before therapy, serum thyroxine (T4) and thyroid-stimulating hormone (TSH) values were elevated; serum tri-iodothyronine (T3) value was at the upper limit of normal while %T3 resin uptake and serum free T4 level were both normal. Treatment with L-thyroxine 150 micrograms/dl was not effective. After this was increased to 200 micrograms/d, serum T4 value rose, TSH was still elevated and there was improvement in symptomatology, and a return of both menses and fertility. PMID- 2928863 TI - Stickler's syndrome. A report of a family. AB - Stickler's syndrome is an autosomal dominant condition characterised by degenerative eye and joint diseases. The eye disorders frequently lead to blindness from retinal detachments and there is often associated hearing loss. The condition has not previously been reported in the RSA. Five patients in a family spanning two generations are described. PMID- 2928864 TI - Endobronchial appearance of tracheobronchial amyloidosis. A case report and suggested classification. AB - Tracheobronchial amyloidosis with the co-existence of submucosal plaques and tumour-like masses is reported. The subdivision of tracheobronchial amyloidosis into submucosal plaques and tumour-like masses is questioned since there appears to be no difference in their clinical presentation and pathological appearance. It is suggested that lower respiratory tract amyloidosis should be classified into tracheobronchial, nodular parenchymal and diffuse alveolar septal amyloidosis. PMID- 2928866 TI - Overestimation of tuberculosis cure rates. PMID- 2928865 TI - Raised intracranial pressure in a 16-year-old boy. Report of a case of Behcet's disease. AB - A case of raised intracranial pressure in a 16-year-old boy, caused by superior sagittal sinus thrombosis secondary to Behcet's disease, is presented. A discussion of cerebral venous thrombosis and its relation to Behcet's disease follows. PMID- 2928867 TI - N-nitrosamines, trichomoniasis and cervical cancer. PMID- 2928868 TI - [Positive urine cultures in malnourished children]. PMID- 2928869 TI - The flow/volume curve as a mass screening test with emphasis on quality control. AB - Air flow through the airways is influenced by different mechanical characteristics of the respiratory system and can be affected by pathological changes in the lungs. Lung volume is probably the most important independent variable determining air flow through the airways. Therefore, it is logical that lung volume should form the ordinate of a curve used to demonstrate the variation of airflow through the airways during forced inspiratory and expiratory manoeuvres. The flow/volume curve is in many ways superior to other measurements of lung function for clinical and epidemiological assessments. Most of the problems that have to be overcome in obtaining satisfactory and repeatable flow/volume curves are discussed and illustrated. A computer system which optimises quality control is described. By making use of this system, operator error can be reduced to a minimum. It is recommended that hard copies of the three efforts must be available and that all flow/volume measurements be controlled by a knowledgeable person before the results are entered in the records. PMID- 2928870 TI - Acute colonic pseudo-obstruction. Current diagnosis and management. AB - Twenty-nine patients with acute colonic pseudo-obstruction were treated over a 6 year period. All had gross abdominal distension which followed either serious systemic illness (23 cases), major surgery (4) or trauma (2). The predominant radiological features were disproportionate segmental or localised dilatation of the caecum and proximal colon, with a relative paucity of distal colonic gas. The correct diagnosis was established and mechanical obstruction excluded in the majority of cases (24) by contrast enema examination. In the remaining 5 cases the diagnosis was made on colonoscopy (4) or at laparotomy (1). Successful colonoscopic decompression was achieved in 2 of 4 cases. Eight patients underwent laparotomy and 3 of 4 patients with caecal perforation and peritonitis died. Two of 21 patients treated conservatively died. Persistence of colonic distension beyond 72 hours, caecal diameter greater than 12 cm or overlying abdominal tenderness indicates urgent decompression. Caecostomy is the advised procedure in patients with non-perforated caecal distension. Prompt recognition and treatment of the condition should eliminate delay in decompression and minimise the risk of caecal perforation. PMID- 2928872 TI - [The value of pinhole collimator imaging in the scintigraphic analysis of vertebral diseases]. AB - Recent findings suggested a possible role for pinhole collimator scintigraphy to differentiate between metastases, infection and fractures of the vertebrae. The aim of this study was to verify these findings and to ascertain whether we could identify any other specific scintigraphic patterns. The study group consisted of 58 patients. A metastatic pattern was obtained in 18 patients, while 16 showed the compression fracture pattern, 3 the tuberculosis pattern and 1 the pyogenic infection pattern. The study was considered normal in 4 patients and showed a nonspecific pattern in 4. Sensitivity was 85% for the metastatic pattern and 83% for the compression fracture pattern. Specificity was 94% for both patterns. Unique new patterns were identified in Paget's disease and in degenerative disease of the vertebrae (12 patients). Pinhole scintigraphy of the vertebrae is a valuable aid for detecting specific diseases of the vertebrae. Our findings suggest a valuable new role for skeletal scintigraphy, improving the specificity and obviating, in most cases of vertebral disease, the need for additional investigations. PMID- 2928871 TI - Crouzon's disease. Part I. One-stage correction by combined face and forehead advancement. AB - Crouzon's disease results in maxillary hypoplasia and a receding forehead, which produce characteristic exorbitism. Total correction of the deformity by Le Fort III osteotomy and face advancement with a simultaneous forehead advancement corrects all the deformities. The advantages and disadvantages of this major craniofacial procedure are discussed after 2 case descriptions. PMID- 2928873 TI - Prevention of stress ulcer by intragastric glucose. An experimental study. AB - Stress ulcer is a condition seen after major trauma and surgery, sepsis, shock and extensive burns so its prevention is very important. Cimetidine and antacids are the drugs most often administered for prevention. Sometimes these drugs are insufficient and complications and side-effects appear. In order to prevent stress ulcers, experimental administration of intragastric glucose has been tested. A 30% dextrose solution given intragastrically decreased both luminal acidity and mean ulcer index. Similar results were obtained with intragastric 0.9% NaCl. The results showed that a luminal factor, not identified in this experiment, is present. PMID- 2928874 TI - Multidisciplinary intensive care unit at Cecilia Makiwane Hospital, Mdantsane, Ciskei. AB - The role of a multidisciplinary intensive care unit in respect of patient care in a developing country is described. An analysis of 1,000 admissions to the unit by severity of disease according to the classification system of Acute Physiology and Chronic Health Evaluation (Apache II), and the short-term outcome of the patients is outlined. The most important referring specialties were surgery (62.7%), medicine (23.9%), paediatrics (7%) and obstetrics and gynaecology (6.4%). Despite the shortage of equipment and investigative facilities, 86.1% of patients were discharged in a satisfactory condition. PMID- 2928876 TI - Methylphenidate in children with the attention deficit disorder. PMID- 2928875 TI - Mesenchymal hamartoma of the liver. A report of 5 cases. AB - Mesenchymal hamartoma of the liver is a rare benign tumour of childhood, characterised by an admixture of ductal structures within a copious loose connective tissue stroma. Less consistent features include hepatocytes and haemopoietic elements. The stroma has a propensity to accumulate fluid and to create macroscopic cystic spaces. Five cases are reported. PMID- 2928877 TI - How to make a million in private practice. PMID- 2928878 TI - Aortic arch interruption in the neonate, with emphasis on early diagnosis and management. AB - Interruption of the aortic arch (IAA) is a rare but lethal congenital cardiovascular anomaly. Over a 3-month period we encountered 5 neonates with IAA, all of whom presented in the 1st week of life with congestive cardiac failure and diminished or absent pulses. All 5 underwent surgery, and 3 died from causes unrelated to the surgical repair. The diagnosis of this condition is difficult to make, although the absence of pulses may provide an important clinical clue (particularly if the left brachial and femoral pulses are involved). Using prostaglandins to re-establish ductal patency may be life-saving in these patients, since this restores blood flow to the lower trunk and kidneys. Administration of oral prostaglandin E2 to infants in whom this anomaly is suspected before they are referred to a tertiary care centre is therefore vital. PMID- 2928879 TI - Crouzon's disease. Part II. Case report--face and forehead advancement in two stages. AB - A child with severe Crouzon's disease had a markedly retruded forehead with exorbitism, which was treated by radical forehead advancement. At a subsequent operation, the maxillary hypoplasia was corrected by a Le Fort III osteotomy and face advancement. PMID- 2928880 TI - Negative bodily experience and prevalence of depression in patients who request augmentation mammoplasty. AB - Increasing numbers of women seek to improve their physical appearance through augmentation mammoplasty (AM), often as a result of underlying psychological problems. Because of methodological problems in many studies, the reported prevalence of psychopathology in these patients varies widely. This study was designed to ascertain the presence of negative bodily experience and depression in patients requesting AM. The study cohort of 30 patients (mean age 30,4 years) was matched and compared with a hospital control group (mean age 30,8 years) who had never requested AM and had been admitted for minor surgery. The two groups were sociodemographically equivalent, the typical patient being a relatively well educated white housewife. Each patient underwent individual psychological assessment, which included a semistructured interview, mental status examination and administration of the Beck Depression Inventory. Apart from several psychological problems related to a negative bodily experience, results indicated that varying degrees of depression were present to a significant extent in most patients seeking AM, emphasising the need for careful pre-operative psychological assessment and treatment of those patients who may require it. PMID- 2928881 TI - Observations on the bite of the southern burrowing asp (Atractaspis bibronii) in Natal. AB - The burrowing asp, Atractaspis bibronii, causes a significant proportion of cases of snakebite near Empangeni, Natal. Data from 8 cases are presented. All were in rural Zulus, and the bites were usually inflicted on the foot during summer nights, in or near the patient's home. There was no sexual bias, but over 50% of the victims were under 14 years of age. Envenomation was mild, characterised by moderate to intense pain and localised swelling, regional lymphadenopathy with occasional discoloration, blistering or necrosis at the bite site. Neurological signs were absent, but symptoms of headache, painful eye movements, dry mouth and hoarseness were recorded. Minor haematological abnormalities were detected in a few patients. Treatment involved analgesics and limb elevation, with antibiotic cover and intravenous fluids when necessary. Antivenom is not effective and was not used. There were no deaths. PMID- 2928882 TI - Phenytoin auto-induction? Case reports. AB - Auto-induction of phenytoin metabolism is considered by many to be insignificant. Two cases, in which elimination of phenytoin apparently increased with continuous use, are presented. The first patient showed an increase in elimination capacity (Vmax) from 511 mg/d to 613 mg/d over a period of 5 months. The second patient showed an increase in Vmax from 512 mg/d to 570 mg/d over a period of 1 year. In neither case was compliance in question. The recognition that therapeutic failure may be due to enzyme induction could obviate expensive diagnostic procedures as well as narrow down the therapeutic alternatives. PMID- 2928883 TI - Neuroblastoma in adults. A report of 3 cases. AB - Well documented as one of the more frequent tumours of childhood, neuroblastomas in adults are rare. Correct diagnosis, and distinction from other small-cell neoplasms, is thus often delayed. Three further cases are described in 2 women and 1 man between the ages of 26 years and 47 years. Metastatic disease existed at the time of initial presentation in 1 patient, while another had experienced multiple recurrences at the primary site before correct diagnosis. All, however, had a favourable response to chemotherapy, albeit in the short term. Primary diagnosis was made by fine-needle aspiration cytology, together with electron microscopic evaluation of aspirated cells in 1 case. The histological, cytological and electron microscopic characteristics of neuroblastomas are presented and illustrated, and their differentiation from other small cell tumours in adults discussed. PMID- 2928884 TI - Acute febrile neutrophilic dermatosis (Sweet's syndrome). A report of 2 cases. AB - Two cases of Sweet's syndrome are described. The diagnostic criteria, clinical spectrum, complications, pertinent differential diagnoses and treatment modalities of this relatively rare clinical condition are described. The association of Sweet's syndrome with underlying haematological malignant disease is stressed. PMID- 2928888 TI - AIDS education in the RSA. PMID- 2928886 TI - Congenital lymphoedema in a child--an unusual diagnosis of ankle oedema seen at a peripheral hospital. A case report. AB - A patient with congenital lymphoedema--the clinical picture being that of Milroy's disease--is presented. The diagnosis, differential diagnosis and treatment are discussed and the modified autosomal dominant mode of inheritance with sex influence and variable expressivity is described. PMID- 2928885 TI - Pulmonary oedema from a widow spider bite. A case report. AB - The clinical course of a patient bitten by a widow spider (Latrodectus indistinctus Pickard-Cambridge (Araneae: Theridiidae] is described. Although this spider is common in southern Africa, case reports are rare. To date details of the development of pulmonary oedema after a bite have not been published in South Africa. PMID- 2928887 TI - Amoebic lung abscesses. A case report. AB - A case of multiple amoebic lung abscesses without indication of direct extension from a subclinical liver abscess, which delayed correct diagnosis, is reported. Severe constitutional symptoms, life-threatening haemoptysis and large pulmonary lesions were the prominent clinical manifestations. The response to metronidazole was dramatic. It is postulated that haematogenous spread was responsible. The rarity of this form of amoebiasis is evident on published reports. PMID- 2928890 TI - Entry of HIV infection into the intravenous drug abusing population. PMID- 2928889 TI - HIV survey in Venda. PMID- 2928891 TI - Isoflurane anaesthesia for status epilepticus. PMID- 2928892 TI - The atlanto-axial hook plate. PMID- 2928893 TI - Electrocardiograms of Bushman soldiers--the unusual is commonplace. PMID- 2928895 TI - Amenorrhoea in exercising females. PMID- 2928894 TI - Vaginal intra-epithelial neoplasia following hysterectomy for cervical intra epithelial neoplasia. PMID- 2928896 TI - Circulating megakaryocytes and platelet production. PMID- 2928897 TI - Development and evaluation of a survey-based type of benefit classification for the Social Security program. AB - This attempt to classify Social Security beneficiaries by type of benefit using the new Survey of Income and Program Participation (SIPP) has yielded promising results. Evaluations of the classification algorithm based on comparison of the estimated number of beneficiaries in each of the several categories to independent estimates of the number of beneficiaries indicate that in most instances a high percentage of each category has been identified. For the most part, age and monthly benefit amount size distributions seem reasonable. Furthermore, very few persons in the sample who were identified as Social Security beneficiaries could not be assigned to one or another of the benefit groups. The classification procedure also represents a marked improvement over earlier efforts to classify type of beneficiary that relied on data from the March Supplement to the Current Population Survey (CPS). Most importantly, the benefit classification scheme based on SIPP data appears to provide reasonably reliable distinctions between retired-worker and widow benefits for widowed women and permits the identification of retired-worker benefits for those women dually entitled to retired-worker and spouse benefits. In addition, the distinction between disabled- and retired-worker benefits for recipients aged 62-64 appears to be reasonably reliable, and for women under age 65, the classification procedure distinguishes between disabled-worker benefits on the one hand and widow and widowed mother benefits on the other. Finally, SIPP procedures for identifying minor child beneficiaries yield markedly better estimates than those available from the Current Population Survey. These improvements in the SIPP context are due entirely to the presence of information not collected in the CPS. The enhancement of the SIPP data set in turn resulted directly from an assessment of earlier work carried out by Projector and Bretz in the CPS context and on extensive research into the nature of Social Security reporting errors in the CPS. The superiority of the SIPP data set is linked principally to the presence of three pieces of information: the Medicare BIC, the direct question on reasons for benefit receipt asked of persons under age 65, and the direct measurement of recipiency and amount of benefits for minor children. Other items of some import include self-reported work disability, retirement status (ever retired from a job), previous marital status for currently married women, age first prevented from working due to a health condition, and Supplemental Security Income misreporting items.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2928898 TI - Liver surgery. PMID- 2928899 TI - Surgical anatomy of the liver. AB - Vital intrahepatic structures, especially the large veins, are of special concern to the surgeon. These intrahepatic structures are seldom taught or displayed in anatomy courses, and illustrations are often presented with the posterior surface of the liver facing the viewer, an aspect seldom seen by the surgeon. In this article, the topographical anatomy of the liver is described in a manner most useful to the practicing surgeon. For this purpose, specimens were specifically prepared to demonstrate the vascular anatomy. PMID- 2928900 TI - Liver resection techniques. AB - Liver resection can be safely accomplished using techniques based on a thorough knowledge of anatomy and the use of readily available tools. Preoperative studies can determine resectability in most cases. An aggressive attitude toward resection of localized primary and secondary malignancies is justified by a 5 year survival rate of 25 to 35 per cent in selected patients. If the possibility of carcinoma has been ruled out, most asymptomatic benign tumors can be watched. PMID- 2928902 TI - Surgery for colorectal cancer metastatic to the liver. Optimizing the results of treatment. AB - Overall, hepatic resection appears to be an important means of curing patients with metastatic colorectal cancer isolated to the liver. The only absolute contraindication to surgery was the impossibility of a radical removal of tumor: if residual disease will remain after the hepatic resection, this operation is not indicated. A possible second contraindication to surgery is the presence of tumor in the hepatic or celiac lymph nodes. Such metastases from liver metastases signal a biologic grade of tumor that is almost sure to spread to other sites. However, one patient of the 25 in this group did survive long term when positive lymph node groups were dissected. Further clinical experience with this form of the disease along with trials of regional adjuvant therapies such as intraperitoneal chemotherapy may be needed. The presence of extrahepatic metastases at the time of liver resection should be considered a relative contraindication to this surgery, but if the patient can be made clinically disease free, long-term disease-free survival may result. It seems imperative that all patients with hepatic metastases be evaluated by an experienced hepatic surgeon for a curative resection. If the patient has between one and four metastases, a 25 per cent long-term disease-free survival rate can be expected. Patients who have a radical resection of more than four metastases should be considered to be in an experimental group in whom more data are needed. In our current state of knowledge, making such patients clinically disease free is their only chance for long-term survival. Other factors besides the number of metastases that will affect the prognosis of the patient include the disease-free interval between colorectal resection and liver resection, the pathologic margin of resection on the liver specimen, and the presence or absence of mesenteric lymph node metastases from the primary cancer. These factors should be considered when determining the prognosis in a given patient and should be used as stratification variables in prospective trials. However, from our analysis of available data, these factors should not be considered contraindications to hepatic resection. PMID- 2928901 TI - Experience with resection of primary hepatic malignancy. AB - Our experience with hepatic resection for 106 primary hepatic malignancies has been summarized as a part of a total experience with 411 hepatic resections for various indications. The operative mortality rate (death within a month) was 8.5 per cent in treating primary hepatic malignancy, which is significantly higher than that of treating hepatic metastases (0 of 123 resections). Overall operative mortality of 411 hepatic resection was 3.2 per cent. A high operative risk was noted in patients with gross cirrhosis, trauma, abscess, and large malignant tumors. The 1-, 3-, and 5-year survival rates of patients with primary hepatic malignancy were 68.5 per cent, 45.1 per cent, and 31.9 per cent, respectively. Survival rates of patients with fibrolamellar hepatocellular carcinoma were significantly higher than those of patients with nonfibrolamellar hepatocellular carcinoma. Eighteen patients survived more than 5 years after hepatic resection, 14 of whom had been treated by trisegmentectomy. The most extensive partial hepatectomy, such as right and left trisegmentectomy rather than extended lobectomies, should be used to remove massive tumors with adequate tumor-free margins. PMID- 2928903 TI - Lipid associated sialic acid in plasma in patients with advanced carcinoma of the ovaries. AB - Plasma lipid associated sialic acid (LASA-P) was evaluated in relation to disease status and disease progression in a total of 52 consecutive patients with advanced carcinoma of the ovaries (FIGO stage III and IV). Forty-three individuals with benign gynecologic diseases served as controls. There were three groups. Group 1 included 23 untreated patients who had LASA-P values above normal before debulking operations. Group 2 consisted of 12 patients who completed 12 courses of chemotherapy after debulking operations and presented with negative findings at second look operation (SLO). LASA-P levels were measured in these patients prior to SLO. Eight of 12 patients had normal LASA-P values for a specificity rate of 67 per cent. Four patients had elevated values with no clinical evidence of disease. Group 3 had 17 patients who failed to respond to cytotoxic chemotherapy after initial debulking procedures. All patients in this group had persistent or recurrent disease that was documented at re-exploration or at SLO. Elevated LASA-P levels were noted in 14 of 17 patients for a sensitivity rate of 82 per cent. Rising LASA-P values in serial samples were the only signs of disease recurrence in three of five patients who completed 12 courses of chemotherapy and in whom SLO showed surgical evidence of disease. The predictive value for positive and negative results for all patients were 92.2 and 72.7 per cent, respectively. In spite of the relatively low sensitivity and specificity rates in groups 2 and 3, LASA-P can be used successfully as a valuable adjunct to monitor the course of the disease during treatment in patients with advanced carcinoma of the ovaries. PMID- 2928904 TI - Intraoperative autotransfusion in radical cystectomy for carcinoma of the bladder. AB - From 1984 to 1987, 49 patients with transitional cell carcinoma of the bladder underwent radical cystectomy during which intraoperative autotransfusion was used. Thirty-three patients were observed for a minimum of one year postoperatively; the mean and median follow-up periods in this group were 23.8 and 26.0 months. Twenty-nine of these 33 patients were alive at the time of reporting; 25 were alive with no evidence of disease, and seven had postoperative recurrence of disease, and seven had postoperative recurrence of tumor. Diffused metastatic disease compatible with intravascular dissemination of tumor during autotransfusion did not develop in any of the patients. Intraoperative loss of blood ranged from 400 to 4,000 milliliters; the mean was 1,497, and the median, 1,300 milliliters. The mean volume of autotransfused blood was 492 milliliters. Autotransfusion accounted for 40 per cent of the total transfusion requirements of the patients and proved to be cost effective for the entire study group. Fear of dissemination of tumor has limited the use of intraoperative autotransfusion during surgical procedures for carcinoma. Analysis of our data failed to define any evidence for dissemination of tumor caused by autotransfusion in patients who underwent radical cystectomy. PMID- 2928905 TI - Treatment of carcinoma of the proximal esophagus. AB - Selection of therapy for carcinoma of the proximal esophagus is controversial. We reviewed our experience with 41 patients with carcinoma of the esophagus within 24 centimeters of the incisor teeth to address this issue. Thirty-seven patients had squamous cell carcinoma, three had adenocarcinoma and one patient had a mucoepidermoid carcinoma. Seventeen patients underwent surgical therapy, which consisted of a resection in 15, colonic bypass in one patient and extracorporeal bypass in one. Ten patients underwent postoperative radiation therapy. Radiation therapy was the primary treatment in 23 patients and chemotherapy alone in one patient. The three month mortality rate was similar for patients with tumor resection and for those receiving radiation therapy as the primary treatment. Median survival time for patients undergoing resection and adjuvant radiation therapy was 12 months and seven months for those receiving only irradiation. Statistical analyses were not performed because patients with radiation only had more advanced disease, invalidating comparison. In terms of palliation, ten of the patients who had radiation therapy could eat solid food, seven could only swallow liquids and six had persistent, complete obstruction. All 12 of the survivors who had a resection were able to eat solid food. Although the one month mortality rate is higher for those treated surgically than with radiation therapy, the three month mortality rates are similar. Surgical treatment provides better palliation and a reasonable survival time and is preferred for patients with resectable disease who are physiologically fit enough to undergo operation. A benefit of postoperative adjuvant radiation therapy is undefined but probably present. PMID- 2928906 TI - An anatomic evaluation of the sacrospinous ligament colpopexy. AB - A series of 31 sacrospinous ligament suspensions performed for correction of genital prolapse between 1980 and 1986 is reviewed. The success rate was 81 per cent. A cadaver dissection of the sacrospinous ligament was also performed with the same approach used at operation. This was done to understand better the relationships involved, to identify areas of potential complications and to improve the technique used. A dense fascia covers the coccygeus muscle, and care should be taken not to confuse this with the sacrospinous ligament. The possibility of injury to the nearby vessels and nerves can be avoided with the careful placement of suture through the sacrospinous ligament and two fingerbreadths medial to its insertion on the ischial spine. At the conclusion of the suspension, the vaginal apex should be intimately attached to the coccygeus muscle and sacrospinous ligament complex. The use of absorbable suture has been recommended by some, but the success of the procedure may be increased by using permanent suture. If anatomic relationships of the nearby structures are remembered, sacrospinous ligament suspension can be a safe, effective and relatively simple procedure for the correction of severe prolapse of the vaginal vault. PMID- 2928907 TI - Diagnostic and therapeutic approaches to pyogenic abscess of the liver. AB - A review was conducted of 33 patients with pyogenic hepatic abscesses seen during the past seven years to evaluate the effect of roentgenologic refinements on diagnosis and therapy. Cause, bacterial infection and clinical manifestations were determined. An ultrasonogram was positive in 27 of 29 patients; computed tomographic scan was diagnostic in 20 of 23 patients, and radionuclide studies were positive in eight of 13 patients. Abscesses were confined to the right lobe in 19 patients, to the left lobe in six and were diffuse in eight. In the group of patients with abscesses developing from a biliary route, one patient was successfully managed by roentgenologically controlled drainage while three others required subsequent surgical drainage. Five of seven patients in the biliary route category who were treated with primary surgical drainage were permanently cured. Twelve patients had an abscess emanating from the portal route. In five of these, drainage under roentgenologic control was successful. Two patients upon whom the procedure failed subsequently underwent drainage at operation. Five had primary surgical drainage, and two of these died. All nine patients with post traumatic, cryptogenic abscesses or an abscess evolving from an arterial route were successfully drained surgically. Three patients with multiple or diffuse abscesses were successfully treated by primary hepatic resection. Refined roentgenologic techniques established the diagnosis of pyogenic abscess in almost all instances. Roentgenologically controlled drainage may be therapeutic in some patients, but surgical drainage remains the standard. Resection has been used as primary treatment in selected patients. PMID- 2928908 TI - Critical reappraisal of diagnostic and therapeutic modalities for thoracic outlet syndromes. AB - A brief conceptual history of neurovascular compression in the thoracic outlet with emphasis on surgical intervention is presented. After the description of techniques for the removal of the first rib in 1962 and 1966, an explosion of operations for thoracic outlet syndromes occurred during the next two decades. A critical reappraisal by several experienced surgeons has led to a re-examination of the indications for surgical intervention. Serious complications involving the brachial plexus and the subclavian artery and vein have unfortunately led to widespread litigation. An attempt is made to define the place of diagnostic and therapeutic modalities that will encourage a favorable outcome in most patients. PMID- 2928909 TI - Nonpancreatic primary tumors with metastasis to the pancreas. AB - A retrospective review of 27 patients with metastatic lesions of the pancreas was conducted. Tissue confirmation of the diagnosis was obtained in all patients. The colon and lung were the most common sites of primary tumor, but a wide variety of primary sites was also found. Pain and jaundice were the most common presenting symptoms. Most patients were managed without pancreatic resection. Mean survival time after diagnosis of pancreatic metastasis was 8.7 months. The diagnosis of metastatic tumors to the pancreas should be considered in all patients with a pancreatic mass, particularly in those with a previously diagnosed malignant lesion. PMID- 2928910 TI - Acute cholecystitis occurring as a complication of percutaneous transhepatic drainage. AB - Sepsis is a common occurrence during long term transhepatic biliary drainage. Most of these episodes are attributed to cholangitis, are relatively minor and can be managed nonoperatively. During a 42 month period, nine patients who had sepsis develop after biliary drainage were found to have acute cholecystitis, a complication not previously noted after this procedure. Seven of the nine patients had an underlying malignant lesion, and three of these patients had undergone percutaneous biliary drainage for palliation of unresectable or metastatic tumor. Eight of the nine patients underwent cholecystectomy whereas percutaneous cholecystostomy was used in one patient with an unresectable cholangiocarcinoma. Operative and pathologic evidence of acute cholecystitis was present in all, but only two patients had gallstones. Seven patients survived the surgical procedure and were discharged at an average of 11.7 days postoperatively. Based on this series, we propose that acute cholecystitis should be considered as a source of sepsis in patients undergoing biliary drainage who do not respond to antibiotics and catheter manipulations. Moreover, cholecystectomy should be performed at the time of laparotomy, if prolonged transhepatic drainage is planned for unresectable malignant conditions. PMID- 2928911 TI - An atraumatic tunneling device for implantation of right atrial catheters and ports. PMID- 2928912 TI - A simplified technique for thrombectomy of vein grafts. PMID- 2928913 TI - The Boix-Ochoa antireflux operation in infants with small stomachs. PMID- 2928914 TI - A simple method for closure of a ventriculotomy incision using pericardium. PMID- 2928916 TI - Lateral pericardiotomy for a safer second operation. PMID- 2928915 TI - Improved exposure for dissection of axillary lymph nodes performed in conjunction with lumpectomy for carcinoma of the breast. PMID- 2928917 TI - Multiple meningiomas: a clinical, surgical, and cytogenetic analysis. AB - Eight cases of multiple meningiomas were found in our 13-year series of 148 operated meningiomas. The relative frequency, 5.4%, of multiple meningiomas observed is compared with that in the literature. The clinical presentation, surgical results, and diagnostic tools are discussed. Cytogenetic analysis was performed in five patients (eight neoplastic specimens). No specific abnormality for multiple meningiomas was found, but our results point out the different origin of each tumor and exclude cell migration through the subarachnoid space as a pathogenetic factor in multiple meningiomas. PMID- 2928918 TI - Magnetic resonance imaging of brain contusion. AB - In this study we investigated the time course of brain contusions using magnetic resonance imaging and compared the findings with those of a computed tomography scan. The lesions, which were demonstrated as homogeneous density areas on the computed tomography scan were demonstrated as different intensity areas in the magnetic resonance image. The intensity of the images varied according to the time at which the images were obtained. The findings indicated changes in the nature of the contusions including hematoma hemoglobin, perifocal edema extension, and so on. In conclusion, magnetic resonance imaging is important in the follow-up of chronological change as well as in original diagnosis of brain contusions. PMID- 2928919 TI - Embolization of solitary spinal metastases from renal cell carcinoma: alternative therapy for spinal cord or nerve root compression. AB - Four patients with a solitary vertebral metastasis from a renal cell carcinoma presented with acute spinal cord or nerve root compression. Because of the markedly hypervascular nature of the metastases it was decided to palliate the lesions by transarterial catheter embolization. The embolization reduced the venous blood pool within the tumors, resulting in progressive neurological improvement often lasting for 12 weeks or more. With such palliation, surgical decompression may be obviated, postponed, or at least made manageable. PMID- 2928921 TI - Leukotrienes in experimental spinal cord injury. AB - Leukotrienes are a group of noncyclized fatty acid eicosanoids which are formed from the breakdown of arachidonic acid. They are potent mediators of inflammation and may contribute to secondary injury in the central nervous system. All mammalian tissue including cerebral cortex is capable of synthesizing these; however, clear documentation of leukotriene formation in the spinal cord is lacking. We subjected 55 rabbits to weight drops of 200, 300, and 400 gm/cm, respectively, on an exposed spinal cord. The traumatized spinal cord was removed after periods of 15, 30, and 45 minutes and 1, 2, 4, 8, and 24 hours. Radioimmunoassay for leukotriene B-4 was then performed on the specimens. Significant (p less than 0.05) elevation was noted in the 200 and 300 gm/cm groups with peak levels occurring in the first 4 hours. The 400 gm/cm group showed significant depression of values below control levels from 2 to 24 hours. We conclude that in sublethal central nervous system injury leukotrienes are produced in significant amounts and may contribute to secondary spinal cord injury. PMID- 2928920 TI - Trigeminal neuroma. A report of eleven cases. AB - The clinical features, diagnosis, and management of a series of 11 cases of trigeminal neuroma (four men, seven women; mean age 40 years) are summarized. Symptoms at presentation were generally those of cerebellopontine angle and petrous apex space occupying lesions. Computed tomography scanning and magnetic resonance imaging were found to provide the best preoperative localization of these lesions, allowing better planning of the surgical approach and thereby maximizing tumor exposure, an essential for any attempt at total excision, considering the large size (greater than 3 cm) of these tumors when diagnosed. A retromastoid incision and posterior fossa craniectomy or a combined suprainfratentorial approach was used. Total excision was possible in four cases. In seven cases, a macroscopic clearance was effected (operative mortality nil, excellent outcome occurred in ten of the 11 cases). There has been no clinical evidence of recurrence or ongoing tumor growth despite possibly subtotal excision. PMID- 2928922 TI - A critique of posterior lumbar interbody fusion: 12 years' experience with 250 patients. AB - A comprehensive long-term follow-up analysis of the clinical and radiographic results of posterior lumbar interbody fusion for lumbar disk disease is presented. This 12-year experience with 250 patients is compared with a previous critique of our surgical management of lumbar disk disease by laminotomy and diskectomy alone. The clinical results and complications rates are comparable. However, posterior lumbar interbody fusion significantly reduces the rate of recurrent problems requiring subsequent surgery. Careful technique and judgment are mandatory for success with posterior lumbar interbody fusion. Homologous tissue bank bone grafts were found to be as successful as autogenous bone. Posterior lumbar interbody fusion represents an improvement in the surgical management of lumbar disk disease. PMID- 2928923 TI - Huge meningioma in a child. AB - A case of a 6-year-old boy with a large meningioma is reported. The patient had an enlarged head, the Foster Kennedy syndrome, and roentgenological evidence of increased intracranial pressure. A computed tomography scan and magnetic resonance image showed a huge tumor in the right parietooccipital region. The tumor was totally resected with the involved right transverse sinus in staged operations. Histology was transitional meningioma. The incidence of intracranial meningiomas is low in childhood. The literature is reviewed, and some peculiarities of childhood meningiomas are discussed. PMID- 2928924 TI - Jugular foramen meningioma. AB - A case of jugular foramen meningioma is presented with a review of the related literature. The value of computed tomography in the diagnosis of the lesion and in the planning of the operative approach is discussed. PMID- 2928925 TI - Surgical treatment and radiological consideration of supergiant cerebral aneurysms. AB - We have collected four cases of supergiant cerebral aneurysm, each greater than 6.0 cm in diameter. Two of these cases were saccular aneurysms of the anterior communicating artery and middle cerebral artery, of which the necks were clipped with resection of the aneurysms. Another patient had a fusiform aneurysm of the middle cerebral artery, which was resected accompanied by a reconstructive procedure of cerebral blood flow. The last patient had a fusiform aneurysm of the internal carotid artery. Following internal carotid artery occlusion surgery with superficial temporal artery-middle cerebral artery anastomosis, the aneurysm completely disappeared radiologically within several months. PMID- 2928926 TI - Tecto-cerebellar dysraphia with occipital encephalocele. AB - We report four cases with the rare syndrome of tecto-cerebellar dysraphia with occipital encephalocele. The clinical features seen in these patients included episodic tachypnea and irregular breathing, opsoclonus, ataxia, marked hypotonia of the limbs, coloboma, and polydactyly. All four patients had midline occipital encephalocele. The cranial computed tomography scan showed partial to total agenesis of the vermis with a large communication between cisterna magna and the fourth ventricle. The computed tomography scan also showed partial deficiency of the midbrain tectum. We discuss the clinical and radiological findings and review the literature. PMID- 2928927 TI - Spinal cord compression due to intradural extramedullary aspergilloma and cyst: a case report. AB - A case of thoracic spinal cord compression caused by intradural extramedullary cyst associated with aspergilloma is presented. The specific diagnosis was extremely difficult and required specialized tissue studies. Clinical suspicion of fungal infection, surgical intervention for spinal cord decompression, and tissue biopsy and relentless diagnostic laboratory studies are particular features of this case. PMID- 2928928 TI - Traumatic aneurysm of the supraclinoid internal carotid artery. Case report. AB - A case of traumatic aneurysm of the supraclinoid portion of the internal carotid artery is reported. The diagnosis was established by angiography after delayed subarachnoid hemorrhage, 2 weeks after trauma. Surgical exploration revealed a false aneurysm and a linear defect in the posterior wall of the internal carotid artery. The vessel was repaired with a microvascular suture. Postoperative angiography demonstrated the patency of the artery. PMID- 2928929 TI - Primary empty sella syndrome caused by an abnormal dilatation of the optic recess. AB - A new variety of primary empty sella syndrome is reported. A partial herniation of the optic chiasm into an enlarged empty sella compressed by a dilated optic recess mimicking a cystic tumor was confirmed at operation. The pathogenesis and the treatment of this type of empty sella syndrome are discussed. PMID- 2928930 TI - Bilateral scrotal migration of abdominal catheters: a rare complication of ventriculoperitoneal shunt. PMID- 2928931 TI - Synthesis, antineoplastic activity and biodistribution of boron analogues of amino acids and related compounds. PMID- 2928932 TI - Improvement of solubility of p-boronophenylalanine by complex formation with monosaccharides. PMID- 2928933 TI - Accumulation of porphyrins in cells and tissue: synthesis of boronated porphyrins. PMID- 2928934 TI - Synthesis and in vivo studies of a carboranyl porphyrin. PMID- 2928935 TI - Boronated porphyrins in NCT: results with a new potent tumor localizer. PMID- 2928936 TI - New tumor localizers: advances in the use of low density lipoproteins (LDL). PMID- 2928937 TI - High resolution 10B and 11B nuclear magnetic resonance (NMR) spectroscopy of Na2B12H11SH impurities and metabolites. PMID- 2928938 TI - In vitro immunological activity of a dextran-boronated monoclonal antibody. PMID- 2928939 TI - In vitro and in vivo studies of boron conjugated melanoma affined biochemicals. PMID- 2928940 TI - Pharmacokinetics and tissue distribution of the sulfhydryl boranes (monomer and dimer) in glioma-bearing rats. PMID- 2928942 TI - In-vivo and in-vitro studies of the effects of mercaptoundecahydrododecaborate (BSH) on hepatic cytochrome P-450 mono-oxygenase enzyme activity and on hexobarbital (HXB) induced sleep in mice. PMID- 2928941 TI - Evaluation of selective boron absorption in liver tumors. PMID- 2928943 TI - Gross boron determination in biological samples by inductively coupled plasma atomic emission spectroscopy. PMID- 2928944 TI - Imaging with 11B of intact tissues using magnetic resonance gradient echoes. PMID- 2928945 TI - Dose inhomogeneities at various levels of biological organization. PMID- 2928946 TI - The radiobiology of a nearly pure, high intensity beam of 24 keV neutrons. PMID- 2928947 TI - Pharmacokinetics of BSH in patients with glioma. PMID- 2928948 TI - Distribution of boron in two (B12H11SH)2--infused patients with malignant glioma. PMID- 2928949 TI - Late results of fundoplication for gastroesophageal reflux in infants and children. AB - The Nissen fundoplication (NFP) for the management of severe gastroesophageal reflux (GER) in infants and children has become one of the most frequently performed operations in pediatric surgical centers in the United States. Short term outcome, morbidity, and mortality are consistently favorable in several large series. The long-term success of this procedure is presumed but has not been established objectively. To examine the late results of this operation, 46 infants and children were carefully evaluated more than 5 years after NFP (mean, 6.7 years). Evaluation included parental interview, physical examination, upper gastrointestinal series, and esophageal pH monitoring. The mean age at the time of operation was 4.13 years. Fifty-seven percent of the patients had significant neurologic impairment, and 80% had at least one serious additional medical problem. Twenty-four percent of the children died during the period of follow-up- all but one death related to serious underlying medical problems. Of the 35 survivors, 26 (74.3%) have no symptoms; five (14.3%) have mild symptoms potentially referable to GER that necessitate little if any treatment; four (11.5%) have had symptomatic recurrence of GER necessitating repeat fundoplication. Three of these patients now have no symptoms. Forty-five percent of the patients had at least one postoperative complication. NFP provides efficacious, long-term treatment of GER in infants and children, with acceptable morbidity. Mortality in this group of children is related primarily to associated diseases rather than to GER. PMID- 2928950 TI - Wood smoke inhalation increases pulmonary microvascular permeability. AB - The effect of wood smoke inhalation (SI) on pulmonary vascular permeability was studied in open-chested, anesthetized dogs. Animals were divided into two groups. A prenodal lymphatic vessel was cannulated in group I (n = 7), and baseline (BL) lung lymph flow (QL) and lymph (CL) and plasma (CP) protein concentrations were measured. The animals' lungs were then ventilated with wood smoke for 5 minutes. Left atrial pressure (Pla) was increased above baseline (mean 16.7 +/- 2.2 mm Hg), and the ratio of CL to CP was used to assess endothelial permeability at high lymph flows. There was little change in either QL (BL: 27 +/- 9; SI: 27 +/- 5 microliters/min) or CL/CP (BL: 0.76 +/- 0.03; SI: 0.74 +/- 0.02) after SI at normal Pla. Elevation of Pla caused a significant increase in QL (136 +/- 15 microliters/min), but CL/CP (0.67 +/- 0.02) failed to decrease significantly at high lymph flows. In group II (n = 15) total protein concentration of airway fluid was compared with that of plasma after smoke inhalation, intravenous alloxan, and increased Pla. The ratio of protein concentration in airway fluid to plasma after SI (0.70 +/- 0.07) was greater than that obtained with increased Pla (0.64 +/- 0.07) but less than that after alloxan (0.85 +/- 0.04). These data indicate that SI in the dog results in a moderate increase in pulmonary vascular permeability that is less severe than that induced by alloxan. PMID- 2928951 TI - Effect of incentive spirometry on diaphragmatic function after surgery. AB - Many of the alterations in lung function that occur after upper abdominal surgery are attributable to reduced diaphragmatic activity. This study was undertaken to determine whether incentive spirometry produces a voluntary activation of diaphragmatic movement in patients with postoperative diaphragmatic dysfunction. Inductance plethysmography was used to measure the tidal volumes of the abdomen and chest in eight women before cholecystectomy and on the first and third postoperative days. In resting patients the relative contribution of the abdominal compartment decreased from 0.520 +/- 0.100 preoperatively to 0.274 +/- 0.265 on postoperative day 1 (p less than 0.01), reflecting the effect of surgery on diaphragmatic function. Inspiratory flow (an index of inspiratory drive) was unaltered by surgery during both resting and incentive spirometry breaths, despite changes in tidal volume. Preoperatively, incentive spirometry increased the tidal volume of the abdominal compartment from 141 +/- 26 ml to 285 +/- 188 ml (p less than 0.005) as a result of increased diaphragmatic movement. This effect was not seen postoperatively; instead, postoperative patients responded to incentive spirometry by increasing the tidal excursion of the chest compartment (158 +/- 37 to 630 +/- 253, p less than 0.005), without any increase in abdominal tidal volume. Thus, incentive spirometry failed to increase diaphragmatic movement in postoperative patients. PMID- 2928952 TI - The coincidence of myocardial reperfusion injury and hydrogen peroxide production in the isolated rat heart. AB - To investigate the specific nature and timing of oxygen (O2) metabolite reperfusion injury, we used a rat-heart model (Langendorff's solution, 37 degrees C) and hydrogen peroxide (H2O2)-dependent aminotriazole inactivation of catalase as a measure of myocardial H2O2 before, during, and after ischemia. We found that after ischemia (20 minutes, global, 37 degrees C), ventricular functional loss- as assessed by measurement of developed pressure (DP), +dp/dt, and -dp/dt with a ventricular balloon--occurred at 10 minutes of reperfusion and that myocardial H2O2 production was maximal by this time. Furthermore, H2O2 production did not occur during ischemia, and inhibition of xanthine oxidase by tungsten feeding or infusing a permeable O2 metabolite scavenger during reperfusion (dimethylthiourea) prevented ventricular functional loss. We conclude that (1) reperfusion injury is in part mediated by toxic oxygen metabolites, (2) H2O2 is the central O2 metabolite responsible for reperfusion injury, and (3) the timing of H2O2 production coincides with the timing of ventricular functional loss. PMID- 2928953 TI - Surgical management of fungal peripheral thrombophlebitis. AB - Fungal infection of central venous catheters is well described. Peripheral fungal thrombophlebitis, however, has only been recognized recently, is thought rare, and is poorly characterized as to clinical presentation and treatment. We report the cases of eight patients with peripheral Candida thrombophlebitis. Patients were elderly and critically ill. All had received broad-spectrum antibiotics. Skin colonization appeared the source of contamination. Sepsis, shock, and organ failure were frequent. Physical findings of fungal phlebitis may be subtle, and diagnosis is often delayed. Multiple sites are frequently involved. Treatment necessitates radical excision of suspected veins and systemic antifungal chemotherapy. Persistent fungemia suggests inadequate phlebectomy or the existence of further affected veins. Peripheral thrombophlebitis is probably a common source of fungal sepsis and should be considered in all patients with fungemia. Without aggressive surgical intervention, survival is unlikely. PMID- 2928954 TI - Development of antitumor reactivity in regional draining lymph nodes from tumor immunized and tumor-bearing murine hosts. AB - With use of the weakly immunogenic MCA 105 tumor of the C57BL/6 mouse, the antitumor reactivity of lymphoid cells derived from the regional draining lymph nodes (RLN) of tumor-immunized and tumor-bearing mice was examined. Mice were immunized with an inoculation of viable tumor admixed with Corynebacterium parvum. Excision of tumor immunization sites within 4 days abrogated the development of systemic immunity to reject a tumor challenge. However, excision of the immunization site on day 6 did not interfere with the development of systemic antitumor immunity. In subsequent experiments, tumor immunization sites were excised on day 6 in all mice and the RLN either left intact or excised on day 6 or day 14. The development of systemic tumor immunity was severely impaired if RLN were excised on day 6, indicating the pivotal role of the RLN. Excision of the RLN on day 14 had no impact on the development of systemic immunity, thus indicating that the requirement for the RLN was time dependent. In mice bearing progressively growing tumors, lymphoid cells derived from RLN were examined for therapeutic efficacy in adoptive immunotherapy experiments. Although fresh RLN cells harvested 6 and 14 days after tumor inoculation did not demonstrate inherent therapeutic efficacy, after in vitro sensitization with irradiated tumor cells and interleukin-2, these RLN cells acquired significant antitumor activity in adoptive immunotherapy experiments. These data indicate that RLN are essential in the development of tumor immunity and may be used as a source of therapeutic effector cells for adoptive immunotherapy. PMID- 2928955 TI - The mechanism of acid-induced increases in canine lower esophageal sphincter pressure. AB - Acidification of the gastric cardia has been shown to increase lower esophageal sphincter pressure (LESP). The mechanism by which this phenomenon occurs remains unknown. This study was undertaken to examine the effect and mechanism of action of proximal gastric acidification on LESP in the dog model. In long-term studies, acidification resulted in a significant increase in mean LESP (23.2 cm H2O). Pretreatment with either topical lidocaine or subcutaneous atropine blocked the sphincteric response to acidification. Neither truncal vagotomy and pyloroplasty, proximal gastric vagotomy, antral vagotomy and pyloroplasty, nor circumferential gastric myotomy significantly altered the sphincteric response to acid. Pretreatment with 6-hydroxydopamine or somatostatin also failed to alter the increase in LESP in response to acid. In short-term studies, after gastric transection 5 cm distal to the gastroesophageal junction, acidification of a vagally innervated distal gastric pouch produced a slight decrease in LESP, whereas acidification of the proximal (orad) section of gastric mucosa still resulted in a significant increase in LESP. These studies suggest that the increase in LESP observed with acidification of the gastric cardia is a local mechanism mediated by an intrinsic neural pathway dependent on cholinergic neurotransmission. This phenomenon of local reflex excitation may be another contributing mechanism to the barrier against gastroesophageal reflux. PMID- 2928956 TI - Medicine and the media: social and legislative issues symposium of the Society of University Surgeons. PMID- 2928957 TI - A perioperative technique for detection of retained valve cusps in the in situ vein graft. AB - A problem of the in situ vein bypass technique is the retained value cusp. To ensure that maximum flow has been obtained through the vein graft after valvotomy, a simple perioperative technique has been developed. This consists of infusing normal saline solution into the vein and comparing the distal to proximal (antegrade) flow with the proximal to distal (retrograde) flow under the same conditions. Twelve consecutive in situ vein grafts have been assessed. Antegrade and retrograde flow measurements were similar in four of the grafts but different in eight (40% to 80% reduced retrograde flow). Valvotomy was repeated and subsequent measurements of retrograde flow were similar or greater than the antegrade. The technique described is simple, reproducible, inexpensive, and may prove useful for routine intraoperative evaluation of valvotomy of in situ vein grafts. PMID- 2928958 TI - Massive hemoperitoneum from transhepatic perforation of the gallbladder: a rare complication of cholelithiasis. AB - A 74-year-old woman with known cholelithiasis arrived at our emergency department with mild abdominal pain. During investigation she collapsed with abrupt hypotension. A peritoneal tap revealed frank blood. At urgent laparotomy, there were several liters of blood in the peritoneal cavity and two free gallstones, despite an apparently intact gallbladder. We report the second recorded instance of transhepatic perforation of the gallbladder presenting as massive hemoperitoneum. PMID- 2928959 TI - Duodenal lipoma causing intussusception. AB - Duodenal intussusception and duodenal lipomas are both rare clinical entities. A case of duodenal intussusception caused by a lipoma is presented. The diagnosis of lipoma may be made endoscopically and radiographically using both upper gastrointestinal series and computed tomographic scan. Intussusception in the duodenum may be partial and cause minimal symptoms, but it has distinctive roentgenographic findings. The treatment of symptomatic lipomas may be endoscopic removal, using snare and cautery, or local excision via duodenotomy. Intussusceptions must be reduced operatively. PMID- 2928960 TI - A warning to surgeons who occasionally see hydatid cysts. PMID- 2928961 TI - Modelling afferent connectivity, postsynaptic plasticity, and signal discrimination. AB - We model a small system of hypothetical neurons having ongoing afferent input ("stimulus") short-term refraction/inhibition, and brief-latency intercellular excitatory feedback loops. We incorporate postsynaptic plasticity: synapses onto a given cell are grouped into dendritic "neighborhoods" wherein sufficiently large local postsynaptic potentials sums cause proportional changes in local synaptic efficacy. The efficacies record multiple cell-to-cell and time-to-time correlations. The efficacy patterns fall into several classes, for each of which there is a stereotypical relationship leading from "steady-state" stimuli to corresponding sets of possible "responses" (periodic firing patterns). We examine the system's ability to discriminate between stimuli via firing patterns and to retain information during change of efficacies. There is an optimal region for efficacy configurations inside of which discrimination is good and outside of which the system can be inactive, particularly forgetful, or perseverative. We find that stimulus discrimination is enhanced by divergence and convergence in the pattern of afferent input. Perseverative firing patterns, invoked or suppressed by cotransmitters, can play a role in associative activities of the network. PMID- 2928962 TI - Synaptogenesis in the stratum griseum superficiale of the rat superior colliculus. AB - The time course of synaptogenesis in the visual part of the superior colliculus (SC) of pigmented rats has been studied. The number of synaptic profiles per unit area and volume of neuropil in the stratum griseum superficiale (SGS) was estimated in seven groups of animals at ages 3, 9, 15, 21, 30, 49 and 85 days after birth. At 3 days only 1.5 +/- 0.06 synaptic contacts per unit area and 5.5 +/- 0.18 per unit volume were found. Most of them were immature contacts between growing processes. The density of synaptic contacts increased slowly during the first week. By day 9, 4.1 +/- 0.25 and 13.4 +/- 0.66 synaptic contacts were counted per unit of area and volume, respectively. A rapid synaptic proliferation occurred during the next 3 weeks and there were 7.7 +/- 0.27 and 25.5 +/- 1.04 synaptic contacts per unit area and volume at 15 days, 21.1 +/- 1.70 and 86.4 +/- 5.11 at 21 days, and 25.9 +/- 1.20 and 96.7 +/- 3.48 at 30 days. At the same time, the synaptic population gradually acquired more mature morphological characteristics: the pre- and postsynaptic structures became more specialized, the number of synaptic vesicles within presynaptic structures increased, and the synaptic junctional apposition became defined. After 30 days, a decrease in the density of synaptic profiles was recorded: 23.9 +/- 0.44 and 79.8 +/- 1.43 per unit area and volume of neuropil at 49 days and 13.4 +/- 0.53 and 49.7 +/- 2.40 at 85 days, respectively. Thus, after the phase of synaptic proliferation, a significant reduction of synaptic density occurred in the SGS neuropil until it was stabilized at the adult level by the third month of life. Considering the data available on the development of the retinal and visual cortical projections to the SC, the process of synaptic elimination, which takes place after the first postnatal month, does not appear to be directly connected with segregation of these particular projections. PMID- 2928963 TI - Cell cycle analysis in the cardiac and neuroepithelial tissues of day 10 rat embryos and the effects of phosphoramide mustard, the major teratogenic metabolite of cyclophosphamide. AB - Using the autoradiographic technique of percent labeled mitoses (PLM), total cell cycle length (Tc) and length of the cell cycle phases G1, S, G2, and M have been estimated for the neuroepithelium and heart of day 10 rat embryos. The Tc for the neuroepithelium was estimated to be 9.45 hr, consisting of G1 of 1.24 hr, S of 6.15 hr, G2 of 1.34 hr, and M of 0.72 hr. The Tc for the heart was estimated to be 13.37 hr, consisting of G1 of 4.30 hr, S of 7.01 hr, G2 of 1.81 hr, and M of 0.25 hr. Comparison of cell cycle parameters in these two tissues indicates that the longer cell cycle in heart tissue is related primarily to an increase in G1. If embryos are exposed to the major teratogenic metabolite of cyclophosphamide, phosphoramide mustard, cell cycle analysis reveals that the S phase of the neuroepithelial cell cycle is lengthened and cells are either slowed or arrested in G2. PMID- 2928964 TI - Quantitative study of the effects of maternal hyperthermia on cell death and proliferation in the guinea pig brain on day 21 of pregnancy. AB - On embryonic day 21, pregnant guinea pigs were exposed to a 44 degrees C environment for 1 hour. As a result, all brain ventricular zone cells in M phase of the mitotic cycle when heat-shock occurred became immediately pyknotic and all cell division was stopped for 4-8 hr. The pyknotic cells were removed at a definable rate until mitosis resumed, after which removal occurred in an apparently random manner. Long delays in the return to mitosis were related to increased destruction of S-phase cells deep within the ventricular zone and largely confined to the alar lamina. Upon recovery, a rostrocaudal delay in mitosis was apparent, and the number of mitotic figures was increased compared with control numbers for 1 hr, after which they returned to control numbers. It was evident that up to 40% of the cells within the ventricular zone were destroyed following brief maternal heat stress. PMID- 2928965 TI - Teratogenicity of zinc deficiency in the rat: study of the fetal skeleton. AB - Zinc deficiency (ZD) is teratogenic in rats, and fetal skeletal defects are prominent. This study identifies fetal skeletal malformations that affect calcified and non-calcified bone tissue as a result of gestational zinc deficiency in rats, and it assesses the effect of maternal ZD in fetal bone calcification. Pregnant Sprague-Dawley rats (180-250 g) were fed 1) a control diet (76.4 micrograms Zn/g diet) ad libitum (group C), 2) a zinc-deficient diet (0 microgram/g) ad libitum (group ZD), or 3) the control diet pair-fed to the ZD rats (group PF). On day 21 of gestation, laparotomies were performed. Fetuses were weighed, examined for external malformations, and stained in toto with a double-staining technique for the study of skeletal malformations. Maternal and fetal tissues were used for Zn, Mg, Ca, and P determinations. Gross external malformations were present in 97% of the ZD fetuses. No external malformations were found in fetuses from groups C and PF. Ninety-one percent of cleared ZD fetuses had multiple skeletal malformations, whereas only 3% of the fetuses of group PF had skeletal defects; no skeletal malformations were found in fetuses from group C. Some of the skeletal malformations described in the ZD fetuses, mainly affecting non-calcified bone, were not mentioned in previous reports, thus stressing the importance of using double-staining techniques. Examination of stained fetuses and counting of ossification centers revealed important calcification defects in ZD fetuses. These effects were confirmed by lower Ca and P concentrations in fetal bone with alteration of the Ca:P ratio. PMID- 2928966 TI - Developmental study of neural tube closure in a mouse stock with a high incidence of exencephaly. AB - About 17% of embryos and fetuses in the SELH/Bc mouse stock have the anterior neural tube defect, exencephaly. No other malformations are seen. The genetic liability to exencephaly was shown to be probably genetically fixed in the SELH/Bc stock. This means that SELH/Bc embryos with successful neural tube closure are genetically the same as exencephalics. Females were significantly more likely to be affected than males (66% females). The pattern of morphological developmental events during anterior neural tube closure on days 8 and 9 of gestation was compared among 322 ICR/Bc (normal), 304 SWV/Bc (normal), and 265 SELH/Bc embryos. Anterior neural tube closure was found to follow a strikingly different pattern in almost all SELH/Bc embryos than in either of the normal strains or in previous published studies. SELH/Bc embryos lack the initial contact between the anterior folds in the posterior prosencephalon/anterior mesencephalon region (Closure 2). In spite of this, all but 17% manage to close the anterior neural tube by extending caudally the later occurring normal anterior zone of contact and fusion at the most rostral aspect of the prosencephalon (Closure 3) through the region of Closure 2 to meet the zone of closure of the rhombencephalon, Closure 4. Anterior neural tube closure was completed late, and in some SELH/Bc embryos, elevation and fusion in the mesencephalon did not occur at all. In histological sections of six- and eight somite embryos, elevated numbers of pyknotic cells in the neuroepithelium and mesenchyme, and elevated numbers of unstained inclusions in the neuroepithelium were found; but their relationship, if any, to the abnormal pattern of neural tube closure is not clear. PMID- 2928968 TI - Patient expectations and the medical malpractice crisis. PMID- 2928967 TI - Ciguatera intoxication from Texas gulf coast fish. PMID- 2928969 TI - Clearinghouse offers health professionals timely AIDS info. PMID- 2928970 TI - Help wanted: nurses, nurses, nurses! AB - Want ads with a desperate tone are filling classified advertising sections of newspapers throughout Texas. The state's shortage of nurses is there for all to see, spelled out in big, bold type. "Take a new direction." "Built for the future. Designed for your career.... Take your career into the next century." Hospitals lure nurses with a choice of working hours, subsidized transportation, tuition reimbursement, educational programs, bonus programs, relocation assistance, temporary housing, and more. Still, the problem persists. In the worst case scenario, it has reached crisis proportions. In May 1988, in a highly publicized move prompted by the shortage, one Texas hospital was turning away ambulance-borne patients from its emergency room and came to the brink of losing Medicare and Medicaid funding. The Texas Legislature's Special Committee on Post Secondary Medical, Dental, and Allied Health Education has documented the administrator's problem. According to the committee's report, issued in December 1988, "There is one Texas registered nurse for every 418 people in the general population; the national average is one RN for every 200 people." Physicians, nurses, and hospital administrators are vitally concerned with the situation's serious implications for the quality of patient care, and all three groups are searching for solutions. The following article explores the history, causes, and proposed solutions for the problem. PMID- 2928971 TI - Eye banking in Texas. AB - Texas is providing corneal tissue in the 1980s that is quite adequate to meet the needs of all Texas patients. Infrequent maldistribution is corrected by tissue sharing between eye banks, facilitated by a toll-free number in Dallas (800-433 6667) for Texas eye banks to call when they cannot meet a local need. With distribution of tissue through eye banks, no patient need wait when tissue is abundantly available. The most important law aiding corneal tissue procurement has been the 1977 Medical Examiners/Justice of the Peace Act, that permits removal of corneas under controlled conditions. This has been implemented in almost all jurisdictions where medical examiners are active, although only a few counties have the services of a medical examiner. The implementation of this law, particularly in Austin, Dallas, El Paso, Fort Worth, Houston, and San Antonio, has increased previous donations by more than double. PMID- 2928973 TI - Unexpected anemia in a newborn. AB - Hemorrhagic anemia in a newborn is often heralded by some history or clinical findings that allow time to anticipate and prepare for the infant. This article describes the unexpected delivery of an anemic baby and reviews the diagnosis and management of spontaneous fetomaternal hemorrhage in an infant. PMID- 2928972 TI - Polyradiculoneuropathy in transfusion-associated AIDS and dorsal root pathology. AB - A 68-year-old woman developed a clinical picture of a painful subacute polyradiculoneuropathy. Her condition improved dramatically after treatment with plasmapheresis. A few months later she was found to have serologic evidence for the human immunodeficiency virus. This infection was traced to a contaminated transfusion received three years earlier. Postmortem studies disclosed pathology affecting mainly dorsal roots. PMID- 2928975 TI - 1989 Texas Skin Cancer/Melanoma Project. PMID- 2928974 TI - Skin cancer: a primer for the nondermatologist. AB - The rising incidence of skin cancer in the United States has become a significant public health concern. The morbidity and mortality associated with these conditions can be reduced significantly by earlier detection and treatment. All physicians, not just dermatologists, can play a role in this regard. This article is intended to alert practicing physicians to the extent of the problem and to familiarize them with the various forms of skin cancer. PMID- 2928976 TI - Medical services for our financially needy elderly patients. AB - Physicians as a profession are concerned about the health care needs of financially needy elderly patients. A program of voluntary assignment is suggested as the best solution for this problem. Mandated assignment would lead to diminished access to medical care and diminished quality. A voluntary assignment program, in cooperation with senior citizens organizations, offers a cooperative effort to cover the elderly in need of medical care. PMID- 2928977 TI - Penicillin allergy. PMID- 2928978 TI - Adult immunizations--their time has come. PMID- 2928979 TI - [Atopic neurodermatitis]. AB - Neurodermatitis atopica is a skin disease caused by various different factors and which is characterized by the simultaneous presence of different clinical features. The treatment is directed towards the various aetiopathological factors and oriented on the clinical picture. The main symptom is dry skin, which has to be rehydrated and provided with an artificial film of grease. Dermosteroids are the most efficient antiinflammatory agents, but they can only be used as one of various components of a complete neurodermatitis therapy. New knowledge gained over the past few years has shown the important role of Staphylococcus aureus in this condition, and as a result antibiotic therapy has increased in importance. The use of soap, which was previously not recommended, is now considered to be a useful and beneficial addition to the treatment, thanks to the availability of new alkali-free, disinfectant soaps. In certain cases there is a causal connection with exposure to allergens. Besides treatment of the itching, which is crucial for the patient, stabilization of the psychological factor and, if necessary, changes in the patient's environmental situation are extremely important. Substitution of essential fatty acids and UV therapy are discussed. PMID- 2928980 TI - [Ambulatory treatment of psoriasis]. AB - The causes and the pathological mechanisms of psoriasis are only partially understood. The different treatments tend to inhibit the proliferation of the keratinocytes as well as the dermal inflammation. Anthralin ("minute treatment"), tar, corticosteroids, photochemotherapy and retinoids are the most frequently used treatments, some by the general practitioner, other by the dermatologist. PMID- 2928981 TI - [The treatment of varicose ulcers]. AB - The cause of venous ulcer (deep veins and perforans veins valvular damages, muscular and articular pump deficiency) can merely be corrected by compression therapy and, in some cases, surgery. Accompanying diseases have to be treated. Although the efficiency of general and local treatment is limited, it is essential to control it correctly and avoid its side-effects. PMID- 2928982 TI - [Management of acquired nevus-cell nevi in clinical practice]. AB - The alarming increase in the incidence of malignant melanoma and the lack of an effective therapy in metastasizing forms focussed the interest on the early curable stages and the precursors (or tumor markers) of malignant melanoma such as dysplastic nevi. Familial variants of dysplastic nevus syndrome (DNS) are associated with increased risk for malignant melanoma; the significance of sporadic dysplastic nevi, however, remains to be elucidated. Until more is known about which clinically dysplastic lesions, if any, can be left with complete safety, it is reasonable to remove all nevi which one cannot say are with certainty benign. PMID- 2928983 TI - [Treatment of precancerous conditions of the skin]. AB - The precancerous skin lesions are defined clinically. Sooner or later they show the tendency to develop into an actual cancer. The most common epithelial precancerous lesion is the actinic keratosis. Sun-exposure for many years and poor pigmentation of the skin predispose for developing actinic keratosis. For the efficient treatment of epithelial precancerous lesions primarily a clear diagnosis is needed. If the diagnosis is not clear a biopsy or excision followed by histological examination is necessary. The treatment modalities for office procedures are: excisional surgery, curettage, electrocoagulation, dermabrasion and cryosurgery. Ionizing radiation in the form of x-rays may be useful for treatment of elder patients with multiple actinic keratosis and large lentigo maligna. Topical chemotherapy (5-Fluorouracil, trichloroacetic-acid) requires good compliance and frequent follow-up. The follow-up of patients with precancerous skin lesions is mainly on the clinical level. These patients should use sun-protective agents. PMID- 2928984 TI - [Therapy using dermatologic agents]. AB - With dermal preparations the therapeutic effect of the active ingredient is considerably influenced by factors such as the properties of the base and the type and conditions of the skin. In this respect, the correlation between the effect of the bases and the acuteness of the disease is the following: the more acute the disease, the more important the base and the less important the active ingredient. For dermal preparations there is consequently a therapeutic need for a differentiated spectrum of suitable bases. The choice of the appropriate vehicle plays a considerable role in the success of the treatment. The criteria for the selection of suitable vehicles are discussed on the basis of various examples. PMID- 2928985 TI - [Intertrigo--a therapeutic problem circle]. AB - Intertrigo is an inflammatory dermatosis involving the body folds. Predisposing factors include constant friction opposing skin surfaces, obesity, sweating and occlusion. Colonization with bacteria, yeast and dermatophytes may exacerbate the dermatosis. Irritant antiseptics may aggravate intertrigo and provoke an allergic contact dermatitis. Treatment consists in careful drying the skin. Antimicrobial agents topically applied may be helpful. Predisposing factors should be corrected carefully. PMID- 2928986 TI - Effect of three weeks' treatment with budesonide on in vitro contractile and relaxant airway effects in the rat. AB - An investigation was carried out to determine whether the sensitivity of rat tracheal smooth muscle to contractile and relaxant drugs was affected by three weeks' treatment with subcutaneous budesonide before death. Budesonide treatment was associated with a lower thymus weight and a smaller gain in body weight than in control animals. There was, however, no difference in the carbachol concentration-response curves or maximum responses to carbachol of tracheal smooth muscle from control and budesonide treated rats. Isometric and isotonic recordings agreed in these respects. Glucocorticoid treatment did not increase the sensitivity of tracheal smooth muscle to the relaxant drugs terbutaline and enprofylline; if anything there was a tendency for terbutaline and enprofylline to be less potent after budesonide treatment. The data suggest that in vivo effects of glucocorticoids on airway responsiveness to bronchodilating and bronchoconstricting drugs are unlikely to be due to a direct effect on bronchial smooth muscle. PMID- 2928987 TI - Effect of changing dietary sodium on the airway response to histamine. AB - The airway response to histamine has been shown to be related to the 24 hour urinary excretion of sodium. To assess whether this relation is likely to represent a direct causal association a randomised double blind crossover trial of slow sodium (80 mmol/day) was compared with placebo in 36 subjects having a low sodium diet. The dose of histamine causing a 20% fall in FEV1 (PD20) was 1.51 doubling doses lower when the men were taking sodium than when they were taking placebo (p less than 0.05). On the basis of PD10 values, the difference in men was 1.66 doubling doses of histamine (p less than 0.05). There was no corresponding effect in women. Regressing PD10 against urinary excretion of electrolytes with data from the two occasions during the trial and the measurements made before the trial showed a significant association with sodium excretion after allowance had been made for any effect associated with potassium or creatinine excretion, the latter being a marker of the completeness of the urine collection. Again there was no corresponding effect among women. These findings are compatible with the differences in regional mortality data for England and Wales, which show a relation between asthma mortality and regional per person purchases of table salt for men but not for women. PMID- 2928989 TI - Prognostic value of bronchoalveolar lavage in sarcoidosis: the critical influence of disease presentation. AB - There has been considerable disagreement about the prognostic value of bronchoalveolar lavage lymphocyte measurements in patients with sarcoidosis. This study looks at the influence of the type of disease presentation and the time since onset of symptoms on lavage fluid lymphocyte profiles in 99 patients studied at the time of their initial diagnosis. Patients who had an acute inflammatory onset of disease with erythema nodosum (n = 32) or acute uveitis (n = 17) almost invariably had high T lymphocyte helper:suppressor (TH:TS) ratios (mean 10.1, 95% confidence interval 7.7-12.5) and had a higher proportion of T lymphocytes in cells obtained at lavage (40%, 35-46%) than patients with a pulmonary presentation (n = 38) (TH:TS 2.9, 0.2-5.7; T lymphocytes 21%, 15-27%) or those studied after resolution of erythema nodosum (n = 12). The patients with recent erythema nodosum had the highest TH:TS ratios of any group (10.4, 8.1 12.7). Thus lavage T lymphocyte percentage and TH:TS are highest in patients with sarcoidosis studied soon after an acute onset with an inflammatory condition such as erythema nodosum or uveitis. Patients with an acute onset of sarcoidosis have a better prognosis than those with a more insidious presentation. The major influence of type of disease presentation and, in the case of patients with erythema nodosum, of time since onset of symptoms may in part explain why different centres have reported such diverse results regarding the value of bronchoalveolar lavage in predicting outcome in sarcoidosis. Studies where the case mix of patients includes a high proportion of patients with acute onset will not find a high TH:TS ratio or increased numbers or proportions of lavage lymphocytes to be indicators of a poor prognosis. PMID- 2928988 TI - Influence of lung volume in sleep apnoea. AB - The influence of a constant increase in functional residual capacity on apnoea characteristics was studied in patients with the sleep apnoea syndrome. Pulmonary inflation was achieved by applying a continuous negative extrathoracic pressure into a Poncho type respirator. Nine patients slept in the Poncho for two consecutive nights, negative extrathoracic pressure being applied during the second night. There was no difference in the total sleep time, its composition within the different sleep stages, the apnoea and apnoea-hypopnoea indices, or the sleep time spent in apnoea between the two nights. The mean (SD) apnoea duration increased with negative extrathoracic pressure from 25.3 (2) to 30.5 (3) seconds (p = 0.003) and time spent in obstructive apnoea (percentage of apnoea time) from 56 (13) to 75 (8) (p = 0.02). The mixed apnoea time (%) decreased from 37 (7) to 21 (7) (p = 0.02). Despite the increase in apnoea duration, less time was spent below each oxygen saturation value during negative extrathoracic pressure. The results were similar for apnoeic episodes during non-REM (non-rapid eye movement) sleep, whereas no significant modifications were seen during REM sleep. It is concluded that the composition of apnoea time and resulting oxygen desaturation are influenced by lung volume. PMID- 2928990 TI - Rheumatoid arthritis with extensive lung lesions. AB - A man of 74 who had had seropositive rheumatoid arthritis for 10 years presented with dyspnoea and reticular striation in both lung fields. At necropsy two years later there was pulmonary fibrosis with multiple rheumatoid nodules and non specific granulomas. PMID- 2928991 TI - Bilateral clicking ribs. AB - Congenital abnormalities of the ribs, including slipping or clicking rib, are well recognised but rarely give rise to symptoms. Slipping rib has previously been described as a unilateral condition. We report an unusual case of symptomatic bilateral slipping ribs treated successfully by surgery. PMID- 2928992 TI - Chylopericardium as a complication of mitral valve replacement. AB - A patient developed chylopericardium after mitral valve replacement. Although there was early relapse with cardiac tamponade it eventually resolved with conservative management consisting of tube drainage initially and a medium chain triglyceride diet for two months. PMID- 2928993 TI - Successful percutaneous balloon occlusion of a large pulmonary arteriovenous malformation. AB - Percutaneous embolotherapy was carried out successfully in a 79 year old woman with a 56% shunt through a single pulmonary arteriovenous malformation. PMID- 2928994 TI - Primary cardiac angiosarcoma causing rupture of the heart and spontaneous bilateral pneumothorax. AB - A patient with a primary cardiac angiosarcoma developed two previously unreported manifestations: cardiac rupture, which has not been reported with any primary cardiac tumour; and spontaneous pneumothorax, which is well recognised with other tumours but has not been reported with a cardiac angiosarcoma. PMID- 2928995 TI - Spontaneous pneumothorax due to metastatic carcinoma of the rectum. PMID- 2928996 TI - Hyaluronan and type III procollagen peptide concentrations in bronchoalveolar lavage fluid in idiopathic pulmonary fibrosis. AB - The connective tissue components hyaluronan (hyaluronic acid) and type III procollagen peptide were measured in bronchoalveolar lavage fluid in 22 patients with idiopathic pulmonary fibrosis and 21 healthy control subjects. The patients with idiopathic pulmonary fibrosis had higher concentrations of hyaluronan (median 46 micrograms/l) and type III procollagen peptide (median 0.45 micrograms/l) than the healthy controls (9 and less than 0.02 micrograms/l; p less than 0.001). The patients had normal serum concentrations of hyaluronan and of the procollagen peptide, and albumin concentrations in lavage fluid similar to those of the control subjects. Neutrophil and lymphocyte counts in lavage fluid were increased on average 10 and two fold respectively in the patients with idiopathic pulmonary fibrosis and both correlated with the amount of hyaluronan recovered (p less than 0.05). An inverse correlation was seen between the transfer factor for carbon monoxide and hyaluronan concentrations in lavage fluid in the patients (p less than 0.05). Deterioration in lung function and radiographic progression were seen over six months in 12 of the patients. These patients had higher lavage fluid concentrations of hyaluronan and type III procollagen peptide than the patients whose disease was stable (p less than 0.01). Increased synthesis of hyaluronan and type III procollagen peptide in lung parenchyma may reflect activation or proliferation (or both) of pulmonary fibroblasts in idiopathic pulmonary fibrosis and seems to be linked to the severity and activity of the lung disease. PMID- 2928997 TI - Impaired non-specific delayed cutaneous hypersensitivity in bird fancier's lung. AB - The relation between non-specific delayed cutaneous hypersensitivity and bird fancier's lung was investigated in 13 patients with the disorder. They were compared with 50 subjects who had no reason to have decreased non-specific delayed cutaneous hypersensitivity (control group) and 34 patients with pulmonary sarcoidosis. In addition, 13 patients with bird fancier's lung (11 of the original group) were tested at least one year after avoiding exposure to the causal antigen. Five antigens (candidine, staphylococcal toxoid, tuberculin purified protein derivative, trichophyton, and streptokinase-streptodornase) were injected intradermally (0.1 ml) and the mean weal diameter was measured at 48 hours. The mean weal size was significantly less in the subjects with bird fancier's lung at the time of diagnosis than in the control group (2.23 v 5.66 mm) but did not differ significantly from that of the subjects with sarcoidosis (2.80 mm) or from that of the bird fanciers with no exposure to the causal antigen for one year (2.75 mm). The impairment of non-specific delayed cutaneous hypersensitivity in patients with bird fancier's lung appears to be quantitatively similar to that occurring in sarcoidosis. PMID- 2928998 TI - Cardiovascular and hypokalaemic effects of inhaled salbutamol, fenoterol, and isoprenaline. AB - The cardiovascular and hypokalaemic effects of equal doses of inhaled fenoterol, isoprenaline and salbutamol were compared in eight healthy male volunteers, in a double blind, placebo controlled study. Increasing doses of 400, 600, and 800 micrograms were given from a metered dose inhaler at 15 minute intervals, followed by measurements of heart rate, blood pressure, total electromechanical systole (as a measure of inotropic response), QTc interval, and plasma potassium concentration. After repeated inhalation, fenoterol resulted in significantly greater chronotropic, electrocardiographic, and hypokalaemic effects than either isoprenaline or salbutamol. The maximum inotropic effect of fenoterol was similar to that of isoprenaline. PMID- 2928999 TI - Oesophagogastrectomy in patients over 70. AB - Although the results of oesophageal resection for benign and malignant disease are well documented, the risk of operative death and long term survival in patients over the age of 70 is not well defined. The outcome has been reviewed for 46 patients (23 male, 23 female) aged 70 years or more (mean 74 years) undergoing oesophageal resection during a period of seven years; 16 patients were 75 years or over. All resections were performed with the EEA stapler, except for one cervical anastomosis that was stitched by hand. In 42 patients resection was for malignancy. Six patients died within 30 days of operation or during the initial hospital stay, giving an operative mortality of 13%. Only one of the 16 patients aged 75 years or more died. Cardiopulmonary complications accounted for most of the operative deaths. Patients were scored retrospectively by a multifactual risk factor. Patients who left hospital had a mean preoperative score of 3.66, compared with 15.2 for those who died. Use of such a score may help to improve selection for surgery in this age group. It is concluded that oesophagogastrectomy may be performed in selected patients over the age of 70 years with acceptable mortality, morbidity, and length of hospital stay. PMID- 2929000 TI - Refractory period following bronchoconstriction provoked by histamine in asthmatic subjects. AB - To determine whether refractoriness to histamine induced bronchoconstriction occurs, 20 asthmatic subjects aged 19-50 years were tested. Subjects underwent two histamine challenge tests (1 and 2) on the same day, the second one being given 45-60 minutes after the first, once the FEV1 after test 1 had returned spontaneously to within 90% of baseline. A further "control" histamine challenge test was carried out on a different day at the same time (+/- 2 hours) as test 1. Bronchial responsiveness was recorded as the cumulative dose (microgram) of histamine provoking a 20% fall in FEV1 (PD20), and the ratio PD20 test 2:PD20 test 1 was used to assess refractoriness. The median value of this ratio (2.20) was significantly greater than 1 (p = 0.003), indicating refractoriness at the time of test 2. By contrast the median ratio PD20 control:PD20 test 1 of 1.03 was not significantly different from 1. Refractoriness could not be accounted for by failure to regain the initial baseline FEV1, though such failure may have exaggerated the effect. An increase in PD20 with the second test was observed uniformly in subjects with moderate or high initial PD20 values but not in those with low values. This suggests that there may be a PD20 threshold of the order 25 100 micrograms for refractoriness to occur. Refractoriness could exert an important confounding effect in investigations in which repeated histamine tests are carried out at short intervals. PMID- 2929001 TI - Increased incidence of pulmonary tuberculosis in chronic interstitial lung disease. AB - Of 162 patients with chronic interstitial lung disease, eight (seven of them male) had active tuberculosis. This was 4.5 times higher than the incidence in the general population. The frequency of tuberculosis was similar in patients treated with and without corticosteroids. PMID- 2929002 TI - Malignant primary pulmonary paraganglioma. AB - The histological, immunocytochemical, and electron microscopic findings in a case of malignant primary pulmonary paraganglioma are reported. The existence of this rare tumour is evidence for the presence of pulmonary chemoreceptors. PMID- 2929004 TI - Fall in peak expiratory flow during haemodialysis in patients with chronic renal failure. PMID- 2929003 TI - Occupational asthma in a pharmaceutical worker exposed to penicillamine. PMID- 2929005 TI - Combined use of non-invasive techniques to predict pulmonary arterial pressure in chronic respiratory disease. AB - The value of non-invasive procedures for predicting pulmonary arterial pressure was investigated in 370 patients with chronic obstructive lung diseases and in 73 with fibrosing alveolitis in a combined study at nine centres in six European countries. Measurements included forced expiratory volume in one second, arterial blood gas tensions, standard electrocardiogram, radiographic dimensions of pulmonary artery, right ventricle dimensions by M mode echocardiography, and myocardial scintigraphy with thallium-201; and certain clinical signs were also used. No single variable was correlated closely enough to allow accurate prediction of pulmonary arterial pressure. Four methods were used to incorporate several variables into mathematical functions for predicting pulmonary arterial pressure. In patients with chronic obstructive lung disease multiple stepwise regression explained 49% of the variance in pulmonary arterial pressure but was not useful for prediction. Discriminant analysis allowed patients to be allocated to bands of pulmonary arterial pressure, as did two non-parametric procedures, in which decision trees were established using either the Kolmogoroff-Smirnoff statistic or Fisher's exact test. Patients with a pulmonary arterial pressure of 30 mm Hg or more were identified with a sensitivity of 83% and a specificity of 91%. The non-parametric tests gave better results than discriminant function. A further 54 patients were studied to validate the functions. Of these, 90% with a pulmonary arterial pressure above 20 mm Hg were correctly identified, and 80% of those with a pulmonary arterial pressure above 29 mm Hg. Similar results were obtained in subjects with fibrosing alveolitis. These mathematical functions allow the use of combinations of non-invasive procedures to select from populations at risk of pulmonary hypertension those in whom direct measurement is required. The mathematical functions are capable of further development by incorporation of variables from newer non-invasive procedures. PMID- 2929006 TI - Patient self care in acute asthma. AB - Psychosocial and other factors that may affect patient self care in acute asthma were investigated in 210 asthmatic adults recruited from general practice and hospital clinics. Interviews and self complete questionnaires were used to assess patients' management of a hypothetical slow onset and rapid onset attack of asthma, attitudes to asthma, family support, psychiatric morbidity, recent asthma morbidity, and knowledge of drug treatment. The patients with the highest morbidity from asthma delayed longest before taking appropriate action in the hypothetical acute attack. One in four patients expressed strong feelings of stigma and pessimism about being asthmatic, but attitudes were only weakly associated with behaviour. Other factors showed no significant relation to self care. The results suggest that there is no single important factor or group of factors governing patients' management of acute asthma. Health education might therefore prove more effective if it paid less attention to the possible cause or causes of poor self care and instead offered pragmatic advice on changing behaviour. PMID- 2929007 TI - Inhibition of fibrinolysis by cellular glutathione depletion in the rabbit. AB - The effect of cellular glutathione depletion on fibrinolytic activity in the arterial wall and on the levels of components of the plasma fibrinolytic system was studied in rabbits. Intraperitoneal administration of buthionine sulphoximine (4.5 mmol/kg body wt), an inhibitor of gamma-glutamyl cysteine synthetase, induced a significant reduction in liver glutathione concentrations with a peak decrease of 51% at 7 hours and a progressive return to normal values. The glutathione concentration in aortic tissue was also significantly reduced 7 h after administration of the depleting agent. Fibrinolytic activity in the arterial wall was inhibited following buthionine sulphoximine administration and only reappeared at 24 hours postinjection. Diethyl maleate administration (3.2 mmol/kg body wt i.p.) also depleted liver and aortic glutathione and inhibited fibrinolysis in the arterial wall. Treatment with both glutathione-depleting agents induced a significant reduction in the functional activity of tissue plasminogen activator (t-PA) (-61% and -27% respectively for buthionine sulphoximine or diethyl maleate) and a significant increase in that of plasminogen activator-inhibitor (PAI) (+61% and +27% respectively), while alpha-2 antiplasmin activity was not modified. Our data suggest a modulatory role of glutathione in the release and/or clearance of the components of the fibrinolytic system in the rabbit. PMID- 2929008 TI - Fragments of urinary fibrin/fibrinogen degradation products and cross-linked fibrin degradation products in various renal diseases. AB - In children with several kinds of glomerular disease, fragments of fibrin/fibrinogen degradation products (FDP) and cross-linked fibrin degradation products (XLFDP) in the urine were investigated by autoradiography using western blotting method. Results were compared with selectivity of proteins observed in cases of proteinuria, or with histological findings. Patients with nephrotic syndrome exhibited slightly increased amount of urinary FDP, consisted mainly of X and Y fragments. On the other hand, in cases of proliferative glomerulonephritis, such as acute glomerulonephritis, purpura nephritis, Ig A nephropathy, systemic lupus erythematosus, or hemolytic uremic syndrome, increased FDP, including XLFDP, was detected in the urine. In these cases, FDP was consisted mainly of fragments X, Y, and D-dimer, and could not be correlated with the degree of mesangial proliferation or with urinary protein selectivity. It was concluded that the increased urinary FDP and XLFDP were derived not only from filtration of plasma fibrinogen or FDP, but also from fibrinolysis of intraglomerular fibrin deposits. PMID- 2929009 TI - Autoantibody against platelet glycoprotein IIb/IIIa in a patient with non Hodgkin's lymphoma. AB - An autoantibody to platelet glycoprotein (GP) II b/III a was produced in a 38 year-old woman who had a previous history of the malignant lymphoma of the stomach. The aggregations of the patient's platelets showed losses of the primary waves in response to ADP and epinephrine and marked hypoaggregation in response to collagen, while agglutination by ristocetin was normal. Crossed immuno electrophoresis (CIE) of her platelets solubilized by 1% Triton X-100 revealed an abnormal biphasic precipitate line of GP II b/III a complex. Nine months later, she developed severe thrombocytopenia along with a relapse of the lymphoma in the cervical lymph nodes. The patient's IgG, which was collected during her thrombocytopenic period and purified, inhibited ADP-, epinephrine- and collagen induced aggregations of normal platelets. In CIE, the 125I-labelled IgG of the patient, inserted into the intermediate gel, was incorporated into the precipitation line of the GP II b/III a complex of normal platelets. Radiation treatment to the cervical lymph nodes dramatically normalized both the function and the count of the patient's platelets. From these findings, it is suggested that an autoantibody to the GP II b and/or III a was produced by the lymphoma cells. PMID- 2929010 TI - Induced clot lysis by mini-dose injection of streptokinase in non-perfused arterial segments of rabbits. PMID- 2929011 TI - Evidence for the formation of a trimolecular complex between streptokinase, plasminogen and fibrinogen. PMID- 2929012 TI - [A study of the usefulness of a metabolic profile test in determining the causes of herd problems on dairy farms in The Netherlands]. AB - A metabolic profile test (MPT), consisting of the following parameters of the blood: glucose, urea, beta-hydroxybutyrate, copper, magnesium, calcium, non esterified fatty acids, bilirubin, aspartate amino transferase, whole protein and the protein spectrum of the serum, was performed in twenty-two normal herds (control herds) in the Netherlands. Reference levels were estimated for the above parameters. The study showed that this MPT did not discriminate between normal herds and herds showing production problems or an increased incidence of metabolic diseases. Statistically significant differences between the three laboratories taking part in these investigations were not observed. PMID- 2929013 TI - [Sensitivity pattern of Staphylococcus aureus isolated from quarter milk from cattle]. AB - Strains of Staphylococcus aureus (n = 319) from bovine quarter milk were tested for susceptibility to antimicrobial drugs. The minimum inhibitory concentration (MIC), was determined by agar dilution methods, and the diameter of the inhibition area was determined by agar diffusion methods. In addition beta lactamase production was tested. The strains tested showed resistance to penicillin, (38.4%), oxytetracyclin (21.2%), and streptomycin (11.5%). Little or no resistance was found to the other antimicrobials in this study. A strong correlation between dilution and diffusion methods was calculated for oxytetracyclin: r = 0.88, and for streptomycin: r = -0.90; correlation for penicillin was weaker: r = -0.66. Since 17% of the strains with an MIC for penicillin less than 0.16 mg/L are still able to produce beta-lactamase, we recommend that when antibiotic susceptibility of staphylococci is examined, beta lactamase production should also be tested. Dapsone, a sulfone compound, formerly not considered a chemotherapeutical drug under Dutch law, had an MIC less than or equal to 0.64 mg/L for 85% of the strains. Therefore, we recommend that sulfone compounds should be registered under the new Veterinary Medicines Act. Since the resistance patterns of S. aureus strains to most antimicrobial drugs were the same as those seen in earlier studies, we find no reason to resort to new generations of broad-spectrum antibiotics in routine prevention and treatment of mastitis. PMID- 2929014 TI - [Legal regulations for the testing of animal experiments]. AB - In 1987, the Dutch Secretary of State for Public Health stated before Parliament that in the near future a legal basis will be given to the review-organisation of (intended) experimental studies on animals. The Department of Health Law of the State University of the province of Limburg recently carried out investigations to test the desirability and framework of such a review-organisation. Standards and criteria are laid down in Dutch as well as in international laws, regulations and codes of conduct. In the United States, Canada and several European countries, systems of regulation and review are operative. In the Netherlands, governmental and private initiatives have led to the establishment of experimental-study review committees. However, the functioning and effectiveness of these committees varies markedly. On the basis of the literature and opinions of experts, a concept of a modification of the existing Experimental Studies in Animals Act was formulated, in which experimental study review committees can find a legal basis. PMID- 2929015 TI - [Patients with dyspnea]. PMID- 2929016 TI - [To whom do roentgen photos belong?]. PMID- 2929017 TI - [Premature death in collies and shelties due to liver disease, heredity or coincidence?]. PMID- 2929018 TI - Early cell proliferative and cytotoxic effects of phenacetin on rat nasal mucosa. AB - The oral analgesic drug phenacetin is known to cause nasal and renal tumors in rats when fed in the diet for 2 years at 1.25 or 2.5%. Long-term exposure to chemicals at cytotoxic concentrations may lead to tumor formation secondary to chronic restorative cell proliferation. In the present experiments, cell proliferative and cytotoxic effects on the nasal mucosa were examined after short term phenacetin administration. One week of daily gavage treatment of rats with phenacetin at doses comparable to those used in oncogenicity studies resulted in dose-related increases in DNA synthesis in both respiratory and olfactory mucosa. The increase in respiratory mucosa was due to inflammatory cells in the lamina propria and not proliferation of the respiratory epithelial cells. This observation demonstrates a potentially serious artifact in analytical approaches to DNA synthesis using tissue homogenates. One or two weeks of daily phenacetin treatment resulted in degenerative changes in the olfactory epithelium and necrosis of Bowman's glands. These changes were associated with increases in cell proliferation only in the olfactory epithelium. Two-week daily gavage treatment of rats with phenacetin at 100, 625, or 1250 mg/kg/day increased olfactory epithelial cell replication 62.4, 174, or 763%, respectively. The dose-response relationship for cell proliferation was similar to that of nasal tumor formation. These data suggest that the primary site of phenacetin toxicity within the nose is the olfactory mucosa, with restorative cell proliferation being confined to the epithelial cell layer. The data indicated that early cell proliferative responses may be important in the genesis of nasal tumors and that cell proliferation data may be useful for setting dose levels for oncogenicity studies. PMID- 2929019 TI - Biotransformation, estrogenicity, and steroid structure as determinants of dysmorphogenic and generalized embryotoxic effects of steroidal and nonsteroidal estrogens. AB - A series of nine chemicals of varying structure and estrogenicity was investigated for biochemical determinants of their relative capacities to alter normal embryonic growth and developmental patterns during organogenesis in rats. In order to circumvent the potentially confounding influences of maternal factors, the direct effects of steroidal and nonsteroidal estrogens on cultured whole embryos were compared at concentrations producing readily measurable embryotoxicity but low embryolethality (2-20%). Nonsteroidal estrogens included were diethylstilbestrol (DES), hexestrol (HES), E,E-dienestrol (alpha-DIES), and tamoxifen (TAM). Steroidal estrogens were estradiol 17 beta (E2), estrone (E1), and 17 alpha-ethinylestradiol 17 beta (EE). For comparative purposes, the effects of two essentially nonestrogenic phenols, Z,Z-dienestrol (beta-DIES) and phenol, were also studied. TAM, a weak estrogen which also exhibits antiestrogenic properties, was studied for possible interactive effects with potent estrogens. Prosencephalic hypoplasia was the abnormality most consistently observed and was elicited by each of the chemicals investigated. Embryotoxicity was neither attenuated by TAM nor related to estrogenic potency or steroidal structure, but was strongly and unpredictably influenced by biotransformational determinants. Presence of a cytochrome P450-dependent oxidizing system in the culture medium resulted in marked increases in embryotoxicity of E1, E2, and phenol, only minor increases for beta-DIES and alpha-DIES, but in strikingly decreased effects of EE, TAM, and HES. It produced no statistically significant differences in effects of DES. The results obtained were compatible with the concept that effects of these agents on growth and development during the earlier stages of organogenesis are independent of steroid structure or estrogenic activity but strongly dependent upon pathways and rates of biotransformation of some (but not all) of the parent chemicals. PMID- 2929020 TI - Effect of N-benzyl-D-glucamine dithiocarbamate on the renal toxicity produced by subacute exposure to cadmium in rats. AB - The effect of N-benzyl-D-glucamine dithiocarbamate (BGD) on the renal toxicity produced by subacute exposure to cadmium in rats was studied. Rats were injected sc with CdCl2 (1.5 mg Cd/kg) daily for 26 days and thereafter they received 13 injections of BGD (400 mumol/kg) every other day. Urinary protein concentration and AST activity significantly increased after 20 days of cadmium treatment. The pattern of the increase in the urinary excretion of cadmium after cadmium treatment was consistent with that in the urinary excretion of protein and AST. Urinary excretion of amino acid increased gradually after the cessation of cadmium treatment. BGD treatment significantly decreased the urinary excretion of protein, aspartate aminotransferase (AST), and amino acid. Plasma AST activity was elevated 8 days after the beginning of cadmium treatment, indicating that the hepatic damage occurred prior to the renal damage. In addition, the microscopic examination of renal tissue from cadmium-treated rats revealed the necrosis of the proximal tubular cells. The cadmium concentrations in liver and kidney were significantly decreased by BGD treatment. The results of this study indicate that BGD treatment is effective in decreasing the cadmium concentrations in liver and kidney, resulting in the therapeutic effect on the cadmium-induced renal damage. PMID- 2929021 TI - Presystemic branchial metabolism limits di-2-ethylhexyl phthalate accumulation in fish. AB - Despite the high lipophilicity of di-2-ethylhexyl phthalate (DEHP), fish do not extensively accumulate this ubiquitous environmental contaminant. Experiments with rainbow trout (Salmo gairdneri) fitted with an indwelling cannula showed that the majority of [14C]DEHP did not reach the systemic circulation of the fish, but was present in the exposure water as metabolites. Pharmacokinetic analysis, using a compartmental model that included the gill as a separate metabolic compartment, indicated that DEHP was extensively metabolized as it diffused from water to blood. Isolated perfused gill arches of trout metabolized DEHP in the exposure bath to monoethylhexyl phthalate, demonstrating the ability of the gill to prevent DEHP entry into the fish. The relationship between metabolic clearance and tissue perfusion further suggests that metabolism in the gill can play an important role in determining the accumulation and toxicity of organic chemical pollutants in fish. PMID- 2929022 TI - Incorporation and disappearance of oxygen-18 in lung from mice exposed to 1 ppm 18O3. AB - In this study, 18O3 was used as a tracer for inhaled ozone in mice. The amount of ozone-derived oxygen (ODO) in the lungs was determined by measuring the amount of oxygen-18 in excess of the natural abundance level which remained covalently bound to organic constituents of lung following exposure to 1 ppm 18O3 for less than or equal to 60 min. The rate of disappearance of ODO from the lungs was determined by quantifying the rate of decrease of oxygen-18 in excess of the natural abundance level in lung from mice exposed to 1 ppm 18O3 for 45 min. With exposure to 1 ppm 18O3. ODO accumulated in lung at a rate of 4.38 pmol/mg dry weight/min. Ozone-derived oxygen had a half-life in lung of approximately 6 hr. We estimate that a minimum of 44 pmol of O3 reacted with lung every minute of exposure to 1 ppm O3. PMID- 2929023 TI - Partition coefficients of low-molecular-weight volatile chemicals in various liquids and tissues. AB - Partition coefficients are required for developing physiologically based pharmacokinetic models used to assess the uptake, distribution, tabolism, and elimination of volatile chemicals in mammals. A gas-phase vial equilibration technique is presented for determining the liquid:air and tissue:air partition coefficients for low-molecular-weight volatile chemicals. This technique was developed from two previously described medium:air methods, relied solely on measurement of chemical concentration in the gas phase, and, compared to earlier work, extends the range of chemicals and tissues examined. Partition coefficients were determined with 0.9% saline, olive oil, and blood, liver, muscle, and fat tissues from rats for 55 compounds. Human blood:air coefficients were determined for 36 compounds and several blood:air values were also determined in the mouse and for one compound in the hamster. An approach is described for predicting the tissue solubilities of untested compounds based on oil:air and saline:air coefficients using regression analyses. A similar approach is used to model fat:air coefficients in terms of oil:air values and to model human blood: air coefficients in terms of rat blood:air coefficients. PMID- 2929024 TI - Plasma lipoproteins in cortical versus lacunar infarction. AB - We investigated the relation of plasma lipids to the risk for ischemic stroke by comparing clinical and biochemical characteristics of survivors of cortical (n = 48) and lacunar (n = 36) brain infarction. By analysis of variance, no differences were observed in the concentrations of total cholesterol, triglycerides, low density lipoprotein cholesterol, very low density lipoprotein cholesterol, or apoproteins A1 and B. Patients with lacunar infarction, however, had higher concentrations of high density lipoprotein (HDL)-cholesterol than patients with cortical stroke. This HDL-cholesterol difference was due primarily to a strikingly low HDL-cholesterol content in white patients with cortical stroke. These data suggest that previously demonstrated differences in HDL cholesterol concentrations between patients with ischemic stroke and control subjects without stroke may apply to patients with cortical but not lacunar infarction. Separation of cerebral infarction into subtypes based on mechanism may help clarify lipid-related risk factors in cerebrovascular disease. PMID- 2929025 TI - The potential role for ultrafast cardiac computed tomography in patients with stroke. AB - We studied 40 patients with stroke of potential cardioembolic origin by cardiac ultrafast computed tomography and two-dimensional echocardiography. Cardiac ultrafast computed tomography was more sensitive (positive in eight of 14 instances) than two-dimensional echocardiography (positive in two of 14 instances) for the detection of intracardiac thrombus, which was found in 13 patients. Mitral anular calcification was diagnosed more often by two-dimensional echocardiography (four of five instances) than by cardiac ultrafast computed tomography (one of five instances); this implies a high incidence of false positives for the former. Cardiac ultrafast computed tomography showed that one half of the patients (21 of 40) had coronary artery calcification, indicating a high incidence of coronary atheroma in this patient population. Future studies comparing brain and cardiac pathology with the findings of cardiac ultrafast computed tomography and patient prognosis are needed to define the significance and utility of this technique in patients with stroke. PMID- 2929026 TI - Age-dependent vulnerability of brain choline acetyltransferase activity to transient cerebral ischemia in rats. AB - Male Fischer-344 rats aged 6, 12, or 24 months were subjected to four-vessel occlusion cerebral ischemia to assess age-dependent ischemic vulnerability of cholinergic and GABAergic neurons based on choline acetyltransferase (EC 2.3.1.6) and glutamic acid decarboxylase (EC 4.1.1.15) activities. Activities of both enzymes were similar (p greater than 0.05) in 6- (n = 5) and 12- (n = 5) month old rats. Mean +/- SEM choline acetyltransferase activities in the cortex, hippocampus, striatum, and cerebellum of 6-month-old controls were 75 +/- 5, 123 +/- 9, 415 +/- 9, and 50 +/- 4 nmol acetylcholine/hr/mg protein, respectively, and were 20-30% lower (p less than 0.05) in all brain regions except the cerebellum in 24-month-old controls. Choline acetyltransferase activity was unaffected by ischemia in 6- and 12-month-old rats but was reduced by 30-60% in 24-month-old rats. Mean +/- SEM glutamic acid decarboxylase activities in the cortex, hippocampus, striatum, and cerebellum of 6-month-old controls were 98 +/- 8, 86 +/- 7, 144 +/- 13, and 125 +/- 9 nmol gamma-aminobutyric acid/hr/mg protein, respectively, and 25-35% lower in all regions of 24-month-old controls. After 30 minutes of ischemia and 5 days of recovery, glutamic acid decarboxylase activities were reduced (p less than 0.05) in all brain regions and age groups. However, its activity was decreased (p less than 0.05 compared with age-matched controls) by 55% in the cortex and 79% in the hippocampus of 24-month-old rats compared with 30% and 45% in younger rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2929027 TI - Transvenous perfusion of the brain with verapamil during focal cerebral ischemia in rats. AB - We report on the effect of calcium channel blocker verapamil administered into the inferior cerebral vein in rats 1 hour after occlusion of the middle cerebral artery. Twenty-four rats were divided into four groups of six rats each. Group A rats received no medication. The other three groups received 0.1 mg verapamil/kg/2 hr. Group B rats received verapamil intravenously. Group C and D rats received verapamil and autologous arterial blood by transvenous perfusion of the brain, Group C rats at 100 mm Hg perfusion pressure and Group D rats at 150 mm Hg perfusion pressure. The administration of verapamil started 1 hour after middle cerebral artery occlusion and lasted for 2 hours. Three hours after occlusion, we used double- or single-tracer autoradiography with 4 [18F]fluoroantipyrine or [14C]iodoantipyrine and [14C]alpha-aminoisobutyric acid as tracers to study the brains for local cerebral blood flow and blood-brain barrier permeability changes. Group C showed a significant increase of local cerebral blood flow in the parietal cortex (89%, p less than 0.01) and sensorimotor cortex (64%, p less than 0.05) compared with Group A. Group D showed an extensive and striking increase in local cerebral blood flow of the ischemic cortical and subcortical areas (57-100%, p less than 0.05). Group B showed no significant changes but exhibited further reduction of local cerebral blood flow in the ischemic cerebral hemisphere associated with slightly increased local cerebral blood flow in the nonischemic cerebral hemisphere compared with Group A. There was no change of blood-brain barrier permeability in any group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2929028 TI - Interrelationship of brain edema, motor deficits, and memory impairment in rats exposed to focal ischemia. AB - We investigated the relations of brain edema, ion shifts, motor performance, and memory impairment using a focal ischemia model in rats. Cortical infarction was produced by ligation of the middle cerebral artery and the ipsilateral common carotid artery combined with temporary occlusion of the contralateral common carotid artery for 1 hour. Water content and sodium, potassium, and calcium concentrations were measured until Day 14 after the ischemic insult. Significant edema formation was observed; it peaked on Day 3 (p less than 0.001) and then declined. The tissue sodium concentration changed in a manner similar to that of water content, but the tissue potassium concentration changed in an opposite fashion. Massive accumulation of calcium was detected as early as Day 1 after ischemia (almost four times the normal level). The increased calcium concentration was sustained even up to Day 14. Motor performance examinations performed on Day 3, including inclined plane, balance beam, and prehensile tests, demonstrated significantly reduced (p less than 0.001) motor ability that did recover even by Day 7. Passive avoidance learning was carried out on Day 2, followed by a memory retention test on Day 3. Significant memory dysfunction was observed in ischemic compared with sham-operated rats (p less than 0.001). A high correlation coefficient (r = 0.91, p less than 0.01, n = 13) was obtained between water content and calcium concentration on Day 3. Both the total motor score and the degree of disturbance of the passive avoidance reaction also correlated well with water content. PMID- 2929030 TI - Biosynthesis of leukotrienes in canine cerebral vasospasm. AB - We produced cerebral vasospasm in 29 dogs by the "two-hemorrhage" method of intracisternal injections, 2 days apart, of autogenous arterial blood. Leukotriene (LT) C4, LTD4, and LTE4 were purified from incubated basilar artery, medulla oblongata, hypothalamus, median eminence, and blood clot from around the basilar artery using reverse-phase high-performance liquid chromatography, and the amount of each LT was quantified separately by bioassay with guinea pig ileum. The biosynthetic capacity for total LTs was approximately three times higher in the hypothalamus and median eminence than in the basilar artery and medulla oblongata in the eight normal dogs. In the dogs with subarachnoid hemorrhage, the biosynthetic capacity was increased significantly both before and 2 hours after the second injection of blood on Day 2 and was normal on Day 7 in the basilar artery and medulla oblongata, whereas the biosynthetic capacity was decreased significantly 2 hours after the first and second injections of blood and was increased significantly on Day 7 in the hypothalamus and median eminence. In blood clot the biosynthetic capacity was increased continuously after the first injection of blood. Thus, the biosynthetic capacity for total LTs showed a time- and tissue-specific change after subarachnoid hemorrhage. PMID- 2929029 TI - Hyperglycemia decreases acute neuronal ischemic changes after middle cerebral artery occlusion in cats. AB - Hyperglycemia has been reported to worsen the tolerance of the brain to ischemia, and it has therefore been recommended that patients undergoing neurosurgical procedures not receive glucose-containing solutions. However, whereas most animal studies have used global ischemia models, most neurosurgical procedures are associated with risks of focal rather than global ischemia. We therefore studied the effects of glucose administration in an animal model of focal cerebral ischemia. We anesthetized 20 cats with halothane (0.85% end tidal in oxygen), and a focal cerebral ischemic lesion was produced by clip ligation of the left middle cerebral artery using a transorbital approach. Hyperglycemia (10 cats, mean +/- SEM plasma glucose concentration 561 +/- 36 mg/dl) was established before ligation by infusion of 50% glucose in 0.45% saline; the control group (10 cats, mean +/- SEM plasma glucose concentration 209 +/- 28 mg/dl) received 0.45% saline only. Total fluid administered, mean arterial blood pressure, body temperature, and arterial blood gas values did not differ between the two groups 0, 2, and 6 hours after ligation. The cats were killed 6 hours after ligation, and the area of severe ischemic neuronal damage was determined by microscopic examination of a coronal section at the level of the optic chiasm. The mean +/- SEM area of left cortical severe ischemic neuronal damage was 12 +/- 2% of the left cortex in the hyperglycemic group compared with 28 +/- 5% in the control group (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2929031 TI - Postischemic cerebral microvascular responses to norepinephrine and hypotension in newborn pigs. AB - We examined the effects of 20 minutes' cerebral ischemia on cerebral microcirculatory responses to topical norepinephrine and systemic hypotension in three groups (sham-operated control, 2-3 hours postischemia, and 24 hours postischemia) of anesthetized newborn pigs equipped with closed cranial windows. Cerebral ischemia may eliminate the prostanoid vasodilator system from the cerebral circulation. Norepinephrine (10(-4) M) decreased pial arteriolar diameters similarly in all three groups (27%, 28%, and 21%, respectively), but only the sham-operated group exhibited pial arteriolar dilation in response to hypotension (28% at 33 mm Hg). Two-three and 24 hours after cerebral ischemia, hypotension decreased pial arteriolar diameters (21% and 17%, respectively). In sham-operated piglets, norepinephrine and hypotension increased cortical periarachnoid cerebrospinal fluid prostanoid concentrations. However, neither norepinephrine nor hypotension altered cerebral prostanoid production 2-3 or 24 hours after cerebral ischemia. Therefore, we conclude that after cerebral ischemia, autoregulatory pial arteriolar dilation in response to hypotension is absent, while vasoconstriction in response to norepinephrine is intact. PMID- 2929032 TI - Repeated cranial computed tomographic and magnetic resonance imaging scans in two cases of eclampsia. AB - In two cases of eclampsia with consumptive thrombocytopenia, the maximum increase in blood pressure and the lowest platelet count coincided with the maximum degree of neurologic and neuroradiologic abnormality. Computed tomograms showed decreased attenuation, and T2-weighted magnetic resonance images showed increased signal intensity focally in the cerebral cortex and the deep gray and white matter. Blood pressure, platelet count, clinical status, and roentgenograms normalized completely in both cases. Severe arterial hypertension and disseminated transitory microvascular occlusions presumably caused multiple small foci of brain edema that resolved without remaining detectable ischemic brain damage. PMID- 2929033 TI - Bilateral loss of vision in bright light. AB - We describe four patients with episodic bilateral vision impairment related exclusively to light exposure. Each had angiographically documented bilateral high-grade stenosis or occlusion of the internal carotid arteries. This phenomenon appears to be related to bilateral simultaneous retinal ischemia delaying regeneration of visual pigments in the pigment epithelial layer. It must be distinguished from bilateral occipital lobe ischemia caused by vertebrobasilar system disease. PMID- 2929034 TI - Homonymous hemianopsia due to posterior ischemia as a model for quantification of neurologic deficit. PMID- 2929035 TI - Oral contraceptives and stroke. PMID- 2929036 TI - Collagen deficiency in cerebral aneurysms. PMID- 2929037 TI - [The restless leg syndrome]. AB - The restless legs syndrome (RLS) is characterized by unusual sensations in the lower legs which are difficult to describe. These sensations are experienced in the muscles and bones. They always occur at rest, most frequently at night, and disappear normally on movement. The etiology and pathogenesis are still unknown. The incidence is stated to be 5%. RLS is the fourth most frequent cause of insomnia. Treatment has been empirical. In recent single controlled investigations clonazepam (Rivotril), carbamazepine (Tegretol) and levodopa plus benserazide (Madopar) have all proved to be superior to a placebo and these drugs are, therefore, recommended. Local treatment should, however, be tried initially in all patients. PMID- 2929038 TI - [Stretching in relation to sports and prevention of injuries]. AB - Stretching is a regular item in training programmes and it is employed to increase flexibility, to prevent muscle tenderness, overuse injuries and strains. Stretching is carried out by stretching muscles and connective tissue to the extreme positions of joints. A review of stretching exercises based on the literature is presented in relation to prevention of injuries. The various techniques employed are reviewed. PMID- 2929039 TI - [Paget's osteitis deformans. Epidemiology and clinical picture]. AB - Osteitis deformans is a focal disease of the osteoclasts characterised by increased bone resorption subsequently followed by increased bone formation leading to abnormal bone. A viral etiology seems increasingly probable, but remains unproven. 5-30% of the patients present with symptoms such as pain, deformity and fracture. Hearing loss, nerve- or root-compression, arthrosis and hyperuricaemia may complicate the disease while malignant degeneration, hypercalcemia and high output cardiac failure are rare. The diagnosis is based on X-ray findings but biopsy may be necessary in selected cases. The extent of the disease is revealed by bone scintigraphy and the activity of the disease reflected by urine hydroxyproline excretion and serum alkaline phosphatase. PMID- 2929040 TI - [Food composition and serum lipids in children]. AB - The composition of the diet is considered to be one of the factors which may be of significance in development of ischaemic heart disease. In order to investigate whether the composition of the diet has a greater influence on the cholesterol levels in children than in adults, af 24-hour dietary interview was carried out on 42 children aged 7-11 years who had previously been examined in the childrens' section of the Osterbro investigation. The children were selected in three groups with low, average and high serum cholesterol levels, respectively. The dietary content of energy-providing substances was compared with the cholesterol values measured. In addition, the composition of the diet in other respects was described and was found to contain, on an average, 40% fat, 14% protein and 42% carbohydrate (of which 14% was sugar). The cholesterol intake was 146 mg/1,000 Kcal. The sugar consumption was low as compared with the national average, approximately 62 g/day. The protein consumption was approximately 2 g per kg body-weight per day. The median total energy intake was 8,024 KJ for girls and 8,569 KJ for boys lower than the recommended daily values and corresponded to a low levels of physical activity. This investigation showed a definite linear connection between the fat energy percentage and the serum cholesterol (alpha = 5.26 p less than 0.005) and that intake of saturated fatty acids, in particular can be related to the cholesterol level (alpha = 2.88 and p less than 0.005). A significantly greater fat energy intake was demonstrated in girls (p less than 0.05) in the group with high serum cholesterol levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2929041 TI - [Secondary aorto-enteric fistula]. AB - On the basis of five case histories, the causes, symptoms, investigations, diagnosis and treatment of secondary aorto-enteric fistulae are reviewed. In a patient in whom reconstruction in the aortoiliac segment has been undertaken, recurrent haematemesis and melaena, pyrexia and septicaemia and abdominal pain should lead to investigation for aorto-enteric fistula by means of oesophagogastro-duodenoscopy and radiological investigations if the condition permits this. Otherwise, emergency laporotomy with thorough examination of the intestine should be undertaken. The condition is associated with a considerable mortality but the prognosis is improved by rapid intervention. In cases where aorto-enteric fistula is suspected, the patient should be referred to a department for vascular surgery. PMID- 2929042 TI - [In vitro fertilization and embryo transfer at the community hospital in Arhus]. AB - Treatment of tubal infertility with in vitro fertilization and embryo transfer (IVF-ET) was introduced in the gynaecological/obstetric department of Arhus Municipal Hospital in February 1988. The principles of treatment are described. During the first ten months, 305 therapeutic cycles were carried out and clinical pregnancy occurred in 20.2% of the cycli after transfer of pre-embryos. PMID- 2929043 TI - [Demonstration of urogenital Chlamydia infection by means of the Chlamydiazyme test]. AB - Abbott's recently introduced Chlamydiazyme test which is based on the Elisa principal and cell culture technique was employed with the object of demonstrating urogenital infection with Chlamydia trachomatis in 150 persons. Neither of the methods were optimal. The Chlamydiazyme test had a lower sensitivity and specificity than the cell culture method. PMID- 2929044 TI - [Infectious conjunctivitis. The tear leukocyte esterase reaction (TLE) as a diagnostic aid]. AB - Lacrimal fluid is absorbed on a cottonwool swab. This swab is pressed on the test field for leukocyte esterase on the stix. The colour change is read after exactly one minute. The sensitivity of the test is 90% and the specificity is 98% as assessed on 94 cases of infectious conjunctivitis and 439 normal individuals. The test is suitable for assessing cases of conjunctivitis in view of antibiotic therapy, control of contact lenses etc. PMID- 2929045 TI - [Traumatic rupture of the thoracic aorta]. AB - A man aged 19 years sustained multiple injuries on account of deceleration. Radiography of the thorax revealed increase in width of the mediastinum. Aortography after 1 1/2 days revealed pseudocoarctation of the aorta corresponding to rupture of the aortic isthmus. This investigation should be undertaken on broad indications in patients with relevant injuries and increase in width of the mediastinum. PMID- 2929046 TI - The Appleton Consensus: suggested international guidelines for decisions to forgo medical treatment. AB - Thirty-three physicians, bioethicists, and medical economists from ten different countries met at Lawrence University, Appleton, Wisconsin, to create The Appleton Consensus: International Guidelines for Decisions to Forgo Medical Treatment. The guidelines deal with four specific decision-making circumstances. 1. Five guidelines were created for decisions involving competent patients or patients who executed an advance directive before becoming incompetent, and those guidelines fell into three categories. 2. Thirteen guidelines were created for decisions involving patients who were once competent, but are not now competent, who have not executed an advance directive. 3. Seven guidelines were created for decisions involving patients who are not now and never have been competent, for whom "no substituted judgment" can be rendered. 4. Eleven guidelines were created for decisions involving the scarcity of medical resources, which exists in all communities. Five concepts were identified as being critical in the establishment of priorities given the reality of scarce health resources. PMID- 2929047 TI - [Ethics and newborn infants]. PMID- 2929048 TI - [Disease and health across cultural borders. Esbjerg, 1-2 December 1988]. PMID- 2929049 TI - [AIDS epidemiology]. PMID- 2929050 TI - [Protection of the fertilized human egg, embryo and fetus-- introduction to a debate of the Ethics Board]. PMID- 2929051 TI - [Significance of hereditary factors in the development of coronary heart disease]. PMID- 2929052 TI - Venous gas embolism: time course of residual pulmonary intravascular bubbles. AB - The time course of pulmonary intravascular air emboli was studied in anesthetized dogs. In one series of experiments air was infused into the right atrium at 0.10 ml.kg-1.min-1 or 0.25 ml.kg-1.min-1 for 15 min or given as a bolus injection of 2 ml/kg at 2 ml/sec. In a second series of series of experiments venous air was infused into dogs (0.25 ml.kg-1.min-1, 15 min) ventilated with 100% oxygen for 0, 30, or 210 min before the embolization. After the air infusions the animals were allowed to recover, breathing 70% nitrogen:30% oxygen. At 10-min intervals during recovery, the nitrogen was replaced with nitrous oxide (N2O) for 5 min to expand any residual pulmonary vascular bubbles. Subsequent changes in pulmonary artery pressure (Ppa) and end-tidal carbon dioxide (PETCO2) concentrations, pulmonary vascular resistance (PVR) and carbon dioxide tensions (PaCO2) as a result of the N2O challenges indicated the presence of residual gas bubbles in the pulmonary arterial system. Residual times of the pulmonary bubbles were 24.5 +/- 12.3 min (0.10 ml.kg-1.min-1 air dose), 43 +/- 10.8 min (0.25 ml.kg-1.min-1 air dose), and 17.8 +/- 2.5 min (bolus). The latter two were significantly different from each other. With 100% oxygen breathing the residual times were 19 +/- 2.2 (0 min), 22 +/- 6.7 min (30 min), and 17 +/- 4.0 (210 min). These values were reduced significantly when compared to the dogs ventilated with 30% oxygen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2929053 TI - Lung centroid pressure in immersed man. AB - Upright immersion imposes a pressure imbalance between alveolar and mean external thoracic pressure. Lung centroid pressure (PLC) is defined as the breathing pressure required to remove this imbalance. Static transrespiratory pressure volume relationships were determined in subjects immersed in upright (n = 17) and prone (n = 13) postures. Compliances measured during immersion (1.87 +/- 0.15 liter.kPa-1 upright, 1.87 +/- 0.17 liter.kPa-1) prone) were compared with compliances, obtained over the same volume range, while upright in air (1.84 +/- 0.17 liter.kPa-1). PLC was determined by the horizontal (pressure) displacement of immersed compliance curves. PLC was calculated to be +1.33 +/- 0.11 kPa (+13.6 cmH2O) relative to the sternal notch when upright and -0.69 +/- 0.12 kPa (-7.0 cmH2O) relative to the sternal plane when prone (mean +/- SEM). Upright PLC did not support the widely used value of +19 cmH2O (Jarrett AS. J Appl Physiol 1965;20:1261-1266). Analysis shows that when data from earlier investigations were adjusted for differences in reference pressure, the collective PLC supports the present results. PMID- 2929054 TI - Nerve conduction velocity in man during deep diving to 360 msw. AB - The function of the sensory and motor median nerves was examined in 6 divers during a simulated dive to 360 meters of seawater (msw), with a mixture of helium and oxygen (heliox) as breathing gas. Divers were examined in the compression chamber before the dive, at 360, 300, 240, 130, 50, and 5 msw, and with skin temperatures ranging from 29.2 degrees to 35.2 degrees C. Examinations were performed with superficial stimulating and recording electrodes. Fast sensory nerve conduction decreased with increase in hyperbaric pressure and with decrease in skin temperature. There was no significant correlation between slow sensory conduction and hyperbaric pressure. Distal motor latency increased with increase in hyperbaric pressure and with decrease in skin temperature. The effect of pressure was independent of temperature. No significant functional changes were detected in the main nerve trunk proximal to the wrist or in the F-wave responses. PMID- 2929055 TI - EEG power spectra in rats during compression and during pentobarbital infusion at pressure. AB - The EEG of rats was studied with power spectrum analysis under compression to 71 ATA with He-O2 and during constant rate infusion of pentobarbital at 71 ATA and at surface. During compression the 1-4 Hz delta activity was increased, and 8-11 Hz alpha, 12-14 Hz spindle, and 16-10 Hz low beta activities were reduced compared to control animal recordings. During the course of pentobarbital infusion at 71 ATA, this picture changed: the delta activity was reduced while alpha and spindle activities (barbiturate spindles) increased, considerably more than in the rats studied at surface pressure. The findings may only in part be explained by pressure reversal of anesthesia. PMID- 2929056 TI - Successful use of transureteroureterostomy to salvage ureterosigmoidostomy after anastomotic failure. AB - Four cases are presented of patients who had undergone ureterosigmoidostomy and in whom a unilateral ureteral anastomotic complication developed that was salvaged subsequently by a transureteroureterostomy. Although other forms of urinary diversion are now being utilized routinely in many centers, the ureterosigmoidostomy is still being employed worldwide, and urologic surgeons need to be versed in its potential problems and how to correct them. PMID- 2929057 TI - Surgical success with AMS M800 GU sphincter for male incontinence. AB - Forty-two incontinent males were treated with the surgical implantation of the AMS M800 GU sphincter from 1982 to 1987. Patients' ages ranged from twenty-four to eighty-four years. All patients had the M800 GU sphincter deactivated from six to sixteen weeks post implantation. Patients were followed from seven to sixty months postoperatively with a mean follow-up of 26.2 months. Thirty-two males (76%) were completely continent post insertion of the M800 GU sphincter while 4 men (9%) experienced minimal to moderate stress incontinence. Two patients (5%) were unable to manipulate the device secondary to physical and/or mental incapacity. Four patients (9%) required removal of components or the entire GU sphincter secondary to infection and/or erosion. Two of these men were subsequently reimplanted with the M800 sphincter and are now totally continent. PMID- 2929058 TI - Prevalence and outcome of surgery for female incontinence. AB - A 4.7 percent surgery rate to correct urine loss conditions was found by a large scale survey of sixty-year and older non-institutionalized women in a Michigan county. The initial postoperative results reported by the respondents were 74 percent complete continence and 23 percent partial relief. The long-term self reported outcomes (two years or more post-surgery) were an absolute continence rate of 39 percent and 17 percent with mild incontinence (the median time since surgery was 12 years), whereas the short term (4-23 months, mean 7.1 months) absolute continence rate was 71 percent. The characteristics of the incontinence respondent who had previous surgery showed 70 percent having mixed stress-urge type of incontinence and 66 percent losing urine almost weekly or daily. Bladder emptying symptoms were reported by 30.4 percent of the continent previously operated respondents compared with 13.0 percent of the incontinent previously operated respondents. All continent respondents and 84 percent of the incontinent respondents believed that physicians can help people with a urine loss condition. PMID- 2929059 TI - Silicone foam dressing for penis after reconstructive pediatric surgery. AB - Although silicone foam has been used abroad as an effective means to dress the penis after hypospadias surgery, its use has not been widespread in the United States. We have modified the method to apply the foam in order to facilitate its use. We used this method to dress the penis with silicone foam in 50 boys after reconstructive surgery. The dressing appeared to be effective in restricting edema and hematoma formation. Also, the dressing stabilized the indwelling urethral catheter thereby preventing disruption of the glansplasty. The urethrocutaneous fistula rate (10%) was not reduced by use of the foam. The dressings uncommonly fell off prematurely. The boys appeared to experience little discomfort while the foam was in place and during its removal. PMID- 2929060 TI - Spurious impotence after hypospadias repair. AB - A fifteen-year-old who had undergone multiple hypospadias repairs alleged erectile dysfunction as a result of his surgery. A new method of nocturnal penile tumescence and rigidity monitoring supplied objective evidence to refute this allegation. Attention is drawn to the need for and availability of written documentation when diagnosing the presence or absence of erectile ability. PMID- 2929061 TI - Initiation of vesicoureteral reflux after heminephrectomy for ureterocele. AB - In a male infant profuse flank urine drainage developed after heminephrectomy for ureterocele. Cystograms then showed bilateral vesicoureteral reflux where none had been present preoperatively. The flank drainage resolved promptly after catheter drainage of the bladder. Decompression of a ureterocele may cause initiation of vesicoureteral reflex. PMID- 2929062 TI - Impact of percutaneous renal stone removal on renal function: assessment by urinary lysozyme activity. AB - Lysozyme in the urine in concentrations greater than 3 micrograms per milligram of creatinine reflects renal tubular disease or dysfunction in patients without bowel disease or leukemia. We therefore used urine lysozyme assays to assess renal response to percutaneous nephrostomy and stone removal in 42 patients. Eight patients had striking increases (4.2-21.1 [mean 7.58] micrograms/mg creatinine) immediately after nephrostomy puncture in urine obtained directly from the punctured kidney. Lysozyme declined sharply thereafter and was within normal limits in all cases by postoperative day 3. This increase appeared to result from bleeding into the urine from the tract. Five other patients had lysozymuria on admission, only 1 of whom had a sharp increase after nephrostomy puncture. In the remaining patients, the lysozyme levels remained within normal limits throughout the hospital course. These data are further evidence of the absence of significant deleterious effects of nephrostomy puncture on the kidney. PMID- 2929063 TI - Lumbar ureteral shunt--an unusual cause of ureteral obstruction. AB - In a neurosurgical patient with a lumbar ureteral shunt in place for many years ureteral obstruction and hydronephrosis developed. The shunt tubing was removed surgically from the ureter leaving a portion of the shunt in the subarachnoid space without sequelae. Historically, most patients undergoing this type procedure had an ipsilateral nephrectomy performed at the time of shunt placement; however, this patient did not. It is important to be aware of this "antique" procedure as it may cause urologic complications. PMID- 2929064 TI - Intra-arterial infusion of 5-fluorouracil for recurrent adenocarcinoma of bladder. AB - We report a case of recurrent adenocarcinoma of the bladder treated by intra arterial infusion of 5-fluorouracil (5-FU). The use of this agent in the treatment of adenocarcinoma of the bladder is reviewed. PMID- 2929065 TI - Pyocele of scrotum: consequence of spontaneous rupture of testicular abscess. AB - We report 2 cases of spontaneous rupture of the testis secondary to suppurative epididymo-orchitis. Both cases presented with pyoceles and were treated conservatively by scrotal incision and drainage of the pyoceles. This prolonged hospital stay and increased morbidity, since both patients ultimately required orchiectomy. We believe that a pyocele is an indication for prompt surgical exploration, and if the testis is ruptured, an orchiectomy should be done. PMID- 2929066 TI - Reversible renal hypertension due to renal hygroma. AB - A hygroma of the left kidney was found at surgery in a thirty-five-year-old woman, who presented with anemia, hypertension, and a left abdominal mass. There was a very high sedimentation rate and fine needle aspiration yielded bizarre cells which raised the possibility of malignancy. Compression of the kidney by the cystic structure probably interfered with renal blood flow and was responsible for the elevated blood pressure which receded to normal after removal of the cyst and the left kidney. PMID- 2929067 TI - Rare solitary metastasis to subcutaneous tissue from choriocarcinoma of testis. AB - A rare case of solitary metastasis to subcutaneous tissue from choriocarcinoma of the testis which was predominantly seminoma is reported. The propensity for vascular route of metastasis of this tumor type producing the patient's clinical picture is presented. The human beta chorionic gonadotropin tumor marker elevation to 4,200 units preoperatively fell to normal two weeks postoperatively, suggesting a solitary metastatic site with total tumor extirpation. Nevertheless, it seemed prudent to give chemotherapy because the nature of the metastatic route suggested other microscopic sites of metastasis. The prognosis of this highly malignant neoplasm, while poorest of the array of testis tumors, has improved dramatically with the advent of effective chemotherapy. PMID- 2929068 TI - Metastases to both testicles from prostatic carcinoma six years after radiation therapy. AB - A case is presented of a sixty-nine-year-old man with metastases to both testicles and right epididymis six years after treatment with external beam radiation for Stage C prostatic carcinoma. PMID- 2929070 TI - Use of local anesthesia in operative andrology. PMID- 2929069 TI - Use of urethral drainage tube and dressings in hypospadias repair. PMID- 2929071 TI - Computerized tomography in diagnosis of bladder rupture. AB - Patients with significant pelvic fractures and hematuria must be carefully evaluated for concomitant urinary tract injuries. Computerized tomography may be a useful adjunct to retrograde cystography for diagnosing bladder rupture in those patients with either equivocal or unexpectedly negative findings on cystograms. PMID- 2929072 TI - Computerized tomography of spontaneous forniceal extravasation. PMID- 2929073 TI - Delayed implantation of prostatic cancer after perineal needle biopsy. PMID- 2929074 TI - Video transurethral resection. PMID- 2929075 TI - The veterinary surgeon as a law enforcement officer. PMID- 2929077 TI - Veterinary education in the marketplace. PMID- 2929076 TI - Fasciola hepatica infestation. PMID- 2929078 TI - Wound myiasis caused by Cochliomyia hominivorax in Libya. PMID- 2929079 TI - Necrotising suppurative pyelonephritis in a rottweiler. PMID- 2929080 TI - Coping with blindness. PMID- 2929081 TI - Life after Riley. PMID- 2929082 TI - The Riley report: veterinary education into the 21st century. PMID- 2929083 TI - Milk production, weight changes and blood biochemical measurements in dairy cattle receiving recombinant bovine somatotropin. AB - Fortnightly injections with 500 mg (1.4 ml) of recombinant bovine somatotrophin in 20 dairy cows and heifers at 80 +/- 7 days after calving resulted in increasing milk yields, compared with paired control cows, for three to four days. The advantage was maintained for a further seven to eight days with a decline occurring during the last two to three days before the next injection. The milk yield did not return to the level of the control cows, and the gap between the lactation curves widened as treatment continued, until two to three weeks after the last injection. The cows' response to treatment was greater than the response to heifers. Blood beta-hydroxybutyrate concentrations reflected the higher energy requirements of the treated animals and the weight loss of the treated heifers. Urea-nitrogen concentrations were significantly lower in the treated animals, suggesting that they utilised protein more efficiently. Treated animals had higher inorganic phosphate concentrations, although they remained within the normal ranges. Differences in calcium, magnesium, albumin and globulin concentrations were either statistically or practically not significant. PMID- 2929084 TI - Interpretation of abomasal worm burdens in cattle. AB - The significance of the worm burden in the diagnosis of parasitic gastroenteritis is examined. It is emphasised that the worm population is in a dynamic state with the calf constantly losing part of its worm burden while picking up new infective larvae. The numbers and proportion of late fourth stage Ostertagia ostertagi larvae gives an indication of the success of the animal in controlling its worm burden. During an examination of the worm population it is also necessary to look at the condition and degree of development of adult female worms to assess the efficiency of the calf's acquired resistance to infection. PMID- 2929085 TI - Use of polysulphated glycosaminoglycan in equine lameness. AB - Four cases of equine lameness were treated with intra-articular polysulphated glycosaminoglycan. Two, two-year-old flat racers were treated conservatively after traumatic injury. They subsequently became lame owing to the formation of new bone and osteophytes. Two older steeplechasers were lame owing to degenerative joint disease. The four horses were treated with intra-articular injections of polysulphated glycosaminoglycans and, after three or four injections, they became clinically sound and were able to continue racing with varying degrees of success. PMID- 2929086 TI - AVS debates Riley. PMID- 2929087 TI - A fodder mycotoxicosis of ruminants caused by contamination of a distillery by product with Aspergillus clavatus. AB - Cattle and sheep, grazed successively on the same pasture and given the same supplementary feeding, developed ataxia and several animals became recumbent. Three cattle died within two weeks and the worst affected sheep were killed for laboratory examination. The supplementary diet which consisted largely of a distillery by-product, malt culms, was submitted for mycological examination and fed to two housed lambs. Aspergillus clavatus was cultured from the culms, and both the affected sheep and the housed lambs showed cerebrospinal degenerative changes. The clinical signs and neuropathology were closely similar to a mycotoxicosis, attributed to A clavatus, which is seen infrequently in cattle in France, Bulgaria, South Africa and China. PMID- 2929088 TI - Assessment of the visually read N-acetylglucosaminidase test to detect mastitis in herd surveys. PMID- 2929089 TI - Staphylococcal dermatitis involving the teats of lactating ewes. PMID- 2929091 TI - Riley recommendations. PMID- 2929090 TI - Anthelmintic resistance by Haemonchus contortus to ivermectin in Brazil: a preliminary report. PMID- 2929092 TI - Case of BSE in the Irish Republic. PMID- 2929093 TI - Feline dysautonomia. PMID- 2929094 TI - Probiotics. PMID- 2929096 TI - Demodex mite in a cat. PMID- 2929095 TI - American screwworm fly in Libya. PMID- 2929097 TI - Insurance and pensions. PMID- 2929098 TI - Measles in the cynomolgus monkey (Macaca fascicularis). AB - The measles virus is known to infect several species of monkeys. A group of 87 cynomolgus monkeys (Macaca fascicularis) was screened to observe whether there was an association between measles and the cold symptoms seen in most of the animals. Another 23 monkeys were vaccinated with attenuated measles vaccine and their antibody titres monitored to ascertain whether the vaccine would protect them against measles. PMID- 2929099 TI - Control of oestrus and ovulation in peri-pubertal gilts with allyltrenbolone or a combination of natural gonadotrophins. AB - One-hundred-and-twenty large white X landrace gilts were allocated at random to one of three treatment groups. Treatment A gilts were given an orally active progestogen, allyltrenbolone (Regumate; Hoechst UK) once daily for 18 days from 185 days of age. Treatment B gilts were given a subcutaneous injection of gonadotrophins (400 iu pregnant mare's serum gonadotrophin, 200 iu human chorionic gonadotrophin). (PG600; Intervet Laboratories) at 203 days of age. Treatment C gilts received no exogenous hormones. All the gilts were housed in groups of 10 from 153 days of age, and up to 203 days of age were isolated from boars. From 203 days each group of 10 gilts was subdivided into two groups of five, a boar was accommodated in a pen adjacent to each group of five and daily contact with it was allowed for one hour. Eight gilts in treatment A, five gilts in treatment B and seven gilts in treatment C failed to exhibit oestrus before 233 days of age (P greater than 0.05). The intervals from exposure to the boar to the onset of oestrus for treatments A, B and C were 8.5, 5.5 and 11.0 days respectively (P less than 0.001). Gonadotrophin treatment significantly reduced the time taken by gilts to show oestrus and the variability within the group was significantly less than that in the other two groups. There were no significant differences between the groups in the mean size of their litters. PMID- 2929100 TI - Persistence of the V4 strain of Newcastle disease virus in an open-range flock of chickens. AB - The V4 strain of Newcastle disease virus was introduced into a small open range flock of bantam chickens, by dosing half the birds directly into the crop. As indicated by rises in titres of haemagglutination inhibition antibody, the virus spread to the uninoculated birds and persisted in the flock for two years, infecting chickens that were introduced by natural brooding and rearing. All new clutches of chicks seroconverted by 80 days of age, and the titres of adult birds showed a concurrent rise, suggesting that the chicks were amplifying the virus. The modes of spread and of persistence of the virus were not determined; although cloacal swabs were taken regularly, only one yielded virus. Antibody titres of the inoculated birds remained above the presumptive protective level of 3 (log2) for over a year, whereas the titres of birds infected by contact were generally less than 3. PMID- 2929101 TI - An outbreak of a tetanus-like condition in heifers. PMID- 2929102 TI - Riley recommendations. PMID- 2929104 TI - Veterinary remuneration. PMID- 2929103 TI - RSPCA advertisements. PMID- 2929105 TI - Vaginal prolapse in a camel. PMID- 2929106 TI - Provision of referral services. PMID- 2929107 TI - Water supply for pigs. PMID- 2929108 TI - Southwood calls for monitoring of BSE risk in veterinarians. PMID- 2929109 TI - Fertility of ewes given either melatonin or progestogen sponges. AB - The administration of melatonin via intravaginal sponges is an effective method of advancing the breeding season in ewes. In the present study the fertility of melatonin-treated ewes has been compared with that of ewes induced to ovulate by conventional treatment. On June 25, 15, 15-month-old ewes (group 1) were given intravaginal implants containing melatonin in silastic tubing. On August 8, 13 similar ewes (group 2) were given Veramix sponges which were removed 12 days later, when they were given 500 iu pregnant mare's serum gonadotrophin (PMSG). Two intact raddled rams were introduced to the combined groups on August 21. The mean date of mating was September 3 +/- 1.5 for group 1 and August 21 +/- 0.2 for group 2 ewes. All the ewes in group 1 and 10 in group 2 (77 per cent) were mated. All the ewes were slaughtered approximately 50 days after mating and their reproductive tracts removed. The mean ovulation rates were 2.1 and 2.3 in groups 1 and 2, respectively. The results indicate that conception rates of 87 per cent and 61.5 per cent of ewes put to the ram were obtained in the melatonin-treated and PMSG-treated groups, respectively. At slaughter the melatonin-treated group were found to have a mean of 1.47 live fetuses per ewe put to the ram and the PMSG-treated group a mean of 1.08. It can therefore be concluded that melatonin implantation is an effective method for the advancement of seasonal breeding in anoestrous sheep, and that the fertility achieved is at least as good as that given by conventional progestogen-PMSG treatment. PMID- 2929110 TI - Periparturient diseases and their effect on reproductive performance in five dairy herds. AB - The incidence of periparturient diseases and their effects on the calving to first service interval, the calving to conception interval and the mean number of services per conception were recorded in five Friesian-Holstein herds in the United Kingdom. The incidence rates of milk fever, milk fever followed by endometritis, retained fetal membranes, endometritis after retained fetal membranes, endometritis, or ovarian cysts, were 7.5, 1.4, 1.3, 3.3, 10.1 and 6.7 per cent, respectively, and the affected cows had significantly (P less than 0.05) extended calving to conception intervals (13, 66, 25, 51, 31 and 64 days, respectively) compared with herd-mates. Calving to first service intervals and services per conception were also adversely affected. In spite of treatment, milk fever, endometritis and ovarian cysts had a considerable impact on fertility. Improved methods of treatment and, or, prevention are clearly required. PMID- 2929111 TI - Long-acting oxytetracycline prophylaxis to protect susceptible cattle introduced into an area of Kenya with endemic East Coast fever. AB - Two field trials were carried out in successive years at the Ngong Veterinary Farm, Kenya, in which young cattle, previously unexposed to tick-borne diseases, were introduced into an area with endemic East Coast fever while protected by a series of injections of a long-acting oxytetracycline. In 1984, 12 animals which received injections of 20 mg/kg of the drug on days 0, 7, 14 and 21 after introduction, together with 12 untreated controls, were exposed without tick control until clinical disease occurred. All 12 control animals contracted East Coast fever by day 24 and 10 of them died. Five of the 12 injected animals had detectable parasites, and one of them required antitheilerial treatment. In 1985, four groups of 10 calves were introduced. One group received injections of 20 mg/kg of oxytetracycline on days 7 and 14, one group received injections on days 7, 14 and 21, and a third group received injections on days 7, 12 and 17; the fourth group (controls) had no treatment until clinical disease occurred. By day 35 all the control animals had contracted the disease and one had died despite antitheilerial treatment. Three injections of oxytetracycline suppressed the disease so that mild reactions occurred in only four animals in each group, but two injections failed to prevent severe reactions in two animals and mild reactions in four others.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2929112 TI - Riley recommendations. PMID- 2929113 TI - Veterinary remuneration. PMID- 2929114 TI - Listeria and pasteurisation. PMID- 2929115 TI - Calcofluor white as an aid to diagnosing fungal conditions. PMID- 2929116 TI - Ethylene glycol and glycolate kinetics in rats and dogs. AB - Ethylene glycol (EG) toxicity results from its metabolism to glycolic acid and other toxic metabolites. The accumulation of glycolate and the elimination kinetics of EG and its metabolites are not well understood, so studies with male Sprague-Dawley rats and mixed breed dogs have been carried out. EG was administered by gavage to rats and dogs, which were placed in metabolic cages for urine and blood sample collection at timed intervals. The peak plasma level of EG occurred at 2 hr after dosing and that of glycolate between 4-6 hr. The rate of EG elimination was somewhat faster in rats with a half-life of 1.7 hr compared to 3.4 hr in dogs. The maximum plasma level of glycolate was greater in rats, although the pattern of accumulation was similar to that in dogs. Glycolate disappeared from the plasma at the same time as EG, suggesting a slower rate of elimination of the metabolite than that of EG. Renal excretion of EG was an important route for its elimination, accounting for 20-30% of the dose. Renal excretion of glycolate represented about 5% of the dose. EG induced an immediate, but short-lived diuresis compared to that in control rats. Minimal clinical effects (mild acidosis with no sedation) were noted at these doses of EG (1-2 g/kg) in both rats and dogs. The results indicate that the toxicokinetics of EG and glycolate were similar in both species. PMID- 2929117 TI - Profile of accidental ingestion calls received via a toll-free line on detergent product labels. AB - Accidental ingestion comments received from May 1986 to April 1988 via a toll free telephone line on detergent product labels were profiled to learn the weight of ingesters, the reported ingestion volumes, and the symptoms reported for several different detergent product categories. Most of the ingesters weighed 20 kg or less; however, 10% of the ingesters weighed 70 kg or more. Most detergent product ingestions involved 1 teaspoon of product or less. Reported symptoms varied with product type and ingestion volume. PMID- 2929118 TI - Neurological disorders in sheep during signal grass (Brachiaria decumbens) toxicity. AB - Severe neurological dysfunction was observed in sheep 4 weeks after grazing on Signal grass (Brachiaria decumbens). These neurological disorders included the stamping of forelegs, star-gazing, incoordination, head-pressing against the fence and circling movements. Histologically, numerous vacuolations of various sizes were observed in the white matter of the brain giving rise to a spongy appearance. PMID- 2929119 TI - What was injected?--A suggested analytical protocol. AB - Excision of an injection site, simple solvent extraction of the excised tissue, and direct injection of an aliquot of the solvent into a GC/MS was shown to allow determination of what was injected in 3 separate cases. PMID- 2929120 TI - A comparison of hemoperfusion columns for paraquat. AB - The efficiency of charcoal hemoperfusion (HP) columns during the treatment of paraquat poisoning by continuous hemoperfusion is poorly documented, and fears of saturation of the charcoal by paraquat have led to replacement of the column in as little as 2-4 hr. Four commercially availably HP devices were compared in a prospective study of 54 patients who had ingested paraquat deliberately. The charcoal columns studied were Hemosorba CH-350 (Asahi Medical, Tokyo, Japan), DHP 1 (Kuraray, Osaka, Japan), Adsorba 300 (Gambro Dialysatoren KG, Hechingen, West Germany) and Hemokart-Adult (National Medical Care, Rockleigh, NJ, USA). Plasma paraquat levels were measured at the inlet and outlet 15 min after the commencement of HP, and hourly during the next 12 hr or until HP was ceased (if less than 12 hr). Platelet levels were measured before HP and every 4 hr thereafter. All 4 types showed almost 100% removal at 15 min and maintained this efficiency throughout the period studied. Both DHP-1 and Hemokart-Adult caused minimal thrombocytopenia (mean always greater than 100,000/mm3). Adsorba 300 and Hemosorba CH-350 caused marked thrombocytopenia, and the levels with Adsorba 300 were significantly lower than for DHP-1 and Hemokart-Adult (P less than 0.05). The thrombocytopenia induced by Adsorba 300 often required platelet transfusions or cessation of HP. Commercially available HP columns are not saturated by the paraquat levels met clinically, so longer use of each column should be considered. PMID- 2929121 TI - Carbon monoxide and myonecrosis: a prospective study. AB - Myonecrosis has been reported to occur in patients with carbon monoxide (CO) poisoning, and last year we reported a case of non-traumatic rhabdomyolysis in a patient with CO poisoning secondary to smoke inhalation. We prospectively studied the association between CO poisoning and rhabdomyolysis by obtaining serum creatine kinase (CPK) levels on 65 of 81 consecutive patients (range 20-1315 IU/L) who presented to the University of Illinois Hospital Emergency Room during a 3-month period with CO levels greater than 5.0% (range 5.0%-63.9%). Thiocyanate levels were obtained on 45 patients (range 0-3.5 mg/dl). We found no statistically significant correlation by linear regression analysis between CO level and CPK level in these patients. A subjective complaint of weakness was obtained in 4 patients and physical evidence of weakness was found in 1 of these (this was felt to be secondary to a cerebrovascular accident). In none of these 4 patients was an elevated CPK level noted. We did, however, note an association between thiocyanate level and CPK level by linear regression analysis (p less than 0.02). A power curve was a better fit for this data (r2 = 0.7). This data suggests that serum CPK levels should not be routinely obtained on patients with CO poisoning and that cyanide may play a more important role in non-traumatic rhabdomyolysis associated with toxic inhalation than had previously been suspected. PMID- 2929122 TI - The usefulness of the arterial blood gas in pure carbon monoxide poisoning. AB - In a retrospective study of 49 cases of carbon monoxide (CO) intoxication presented to the University of Illinois Hospital (UIH) Emergency Department between November 1986 and April 1988, we looked for a correlation between carboxyhemoglobin (COHb) as determined by a venous sample and the pH as determined by arterial blood gas analysis. The range of COHb levels in our study was 10-64% (mean 21.8% +/- 10.2%). Smoke inhalation cases (n = 3) were excluded from our study because they did not represent pure CO intoxication. Of the remaining 46 cases, 18 had arterial blood gases drawn. In none of these 18 cases (mean COHb 24.5% +/- 12.6%) did we find a correlation between COHb levels and the pH as determined by linear regression analysis. Also, in none of the 18 cases were there any therapeutic interventions associated with the arterial blood gas result. Additionally, in none of the remaining 28 cases were any therapeutic interventions performed with regards to patients' acidosis or ventilatory status (except 100% oxygen administration. We also retrospectively reviewed records of 104 cases who presented to Cook County Hospital Emergency Department with COHb levels over 10% during the period between March 1986 and May 1988. In these cases, we found no significant correlation between COHb level and arterial pH. We therefore conclude that arterial blood gases drawn in order to determine the degree of acidosis in mild CO intoxication without respiratory distress may not be useful in guiding therapeutic intervention and need not be routinely drawn. PMID- 2929123 TI - Pregnancy outcome following first trimester exposure to cocaine in social users in Toronto, Canada. AB - Studies of drug-dependent women reveal high rates of adverse fetal effects of cocaine. However, no data are available on the effect of the chemical in social users who discontinue cocaine upon realizing they are pregnant. We report the results of the first phase of a prospective study examining the outcome of pregnancy in women seeking counseling from the Motherisk Program in Toronto. Of 25 women seen in our clinic for 1st trimester cocaine exposure, 92% reported use of less than 10 g of cocaine and 36% reported marijuana use. Other illicit drug use was rare; cigarette and alcohol use was common. The study group did not experience adverse pregnancy outcome above the rate expected in the general population. There were 23 single births 1 pair of twins, and 1 spontaneous abortion. Birth weight and gestation were within normal limits. Only 1 child had a major malformation, syndactyly. Infant development was within normal limits, as measured by developmental milestones. All children are scheduled for assessment using the Bayley Scales of Infant Development. The results of the BSID will be compared to results from a cannabis-exposed control group and a no-drug control group. PMID- 2929124 TI - Pharmacokinetics of deferoxamine with and without iron load. PMID- 2929125 TI - Poison center utilization in nosocomial toxicologic exposures: a prospective study. AB - Accidental toxicologic exposures that occur within health care facilities (HCF's) have the potential to increase morbidity and mortality, as well as enhance medicolegal liability. By contacting the poison center immediately on recognition of these events, health care providers may ultimately lessen eventual toxic effects through appropriate intervention. Exposures of this nature reported to the poison center over a twelve month period were collected and tabulated for specific occurrences. Six categories of therapeutic misadventure were delineated: Right patient/wrong medication (18%); Right patient, right medication/wrong dose or route (16%); Lack of patient education (2%); Proximity of potentially harmful substances to confused persons (54%); and Incorrect equipment management (4%). This study seeks to increase awareness of poison center ability to assist in management of the "therapeutic misadventure." PMID- 2929126 TI - Phenytoin toxicity: predictors of clinical course. AB - The records of 46 patients who were admitted to a general hospital with the diagnosis of phenytoin toxicity were retrospectively studied to identify factors present at the time of admission which correlated with severity of illness and which would therefore be of prognostic value. Length of hospital stay was used as a measure of severity of illness. Correlations were made between the length of hospital stay and 18 variables studied at the time of admission, including severity of symptoms, use of other drugs (sedative hypnotics, anticonvulsants and phenothiazines), history (seizures, cardiac arrhythmias, and alcohol abuse), laboratory evidence of liver disease or renal disease, electrolyte abnormalities, coagulopathies, prior suicide attempts, glucose levels, and white blood cell counts. Significant correlations related the length of hospital stay with the severity of symptoms, concurrent phenothiazine usage, and the presence of abnormal liver function tests on admission, but not with other factors studied. Admission phenytoin serum levels following an overdose were not a useful predictor of length of hospital stay in this series of patients. PMID- 2929127 TI - Phenytoin toxicity: a review of 94 cases. AB - Records of all patients admitted to an urban teaching hospital from 1977-1987 with a diagnosis of phenytoin toxicity were reviewed in order to determine indications for admission and discharge, and to assess the need for therapeutic intervention and monitoring. Of 94 patients identified, 57 were male and 37 were female. Ages ranged from 19 mo to 84 yr. Serum phenytoin levels ranged from 21.4 90 micrograms/ml, with a mean level 44.4 +/- 12.5 micrograms/ml. Ataxia was observed in 59/94 patients (63%), and of these 18 patients had fallen; 9 had suffered injury from falling sufficient to require medical care. No other factors were associated with morbidity. No hemodynamic instability was seen in any of the cases. Electrocardiographic records were available for 71/94 cases (76%). There were no abnormalities due to phenytoin. Symptoms of toxicity resolved with supportive care. There were no deaths in this series. Phenytoin is a relatively safe medication even in the toxic range as determined by baseline phenytoin levels. Hospital admission is indicated in symptomatic cases until a declining serum phenytoin level is observed and ataxia resolves. The data in this series do not support routine electrocardiographic monitoring in cases of phenytoin toxicity. PMID- 2929128 TI - Eucalyptus oil: 14 cases of exposure. PMID- 2929129 TI - Serum enzyme disturbances after tricyclic antidepressant overdose. AB - In order to evaluate the enzymes CPK and LDH as potential biochemical markers of tricyclic antidepressant (TCA) cardiotoxicity, we prospectively followed 29 patients with TCA overdose. Serum CPK and LDH were obtained on all patients at admission. Population characteristics included a mean age of 33 y, a mean peak serum TCA concentration of 1190 ng/ml and mean maximal QRS interval of 0.10 sec. Seven patients (23%) had admission hypotension, 7 (23%) had severe respiratory depression, 6 (20%) had seizures and 4 (13%) had cardiac arrhythmias. One patient died. Mean admission CPK was 301 IU/L (nl less than 230 IU/L) while mean LDH was 221 IU/L (nl less than 250 IU/L). In 17 patients (57%), CPK remained in the normal range. There was no correlation between blood pressure, maximal QRS interval, serum TCA concentration, arrhythmias or seizures and CPK or LDH by regression analysis. CPK isoenzymes were obtained in 6 patients (both with and without severe myocardial dysfunction). One patient had an MB fraction of 10%; the remaining 5 had no measurable enzymes of myocardial origin. We conclude that modest elevations in CPK or LDH may occur after TCA overdose. These enzymes do not appear to originate from the myocardium and are of no utility in the assessment of antidepressant cardiotoxicity or prediction of clinical course. PMID- 2929130 TI - Lionfish string experiences of an inland poison center: a retrospective study of 23 cases. AB - From January 1979 through March 1988, our regional poison center, located many hundreds of miles from the nearest coastal salt water, documented 23 cases of envenomation by "Lionfish" (members of genus Pterois). All cases involved specimens which were maintained in the homes of amateur aquarists. A study of patient epidemiology showed the following: patient's sex 91.3% male, 8.7% female; patients ages ranged from 17 to 50 years with an average age for males of 29.8 years and 35 years for females; the site of the envenomation accident was always in the home; the only part of the body envenomated was the hand or finger; and all of the patients were symptomatic. Symptoms noted included sharp pain, swelling, redness, bleeding, nausea, numbness, joint pain, anxiety, headache, disorientation, and dizziness. One patient had a complication of cellulitis. Treatment provided included immersion of the effected area in hot water at 40 C for 60 to 90 min, analgesics, tetanus toxoid, and antibiotics. There were no deaths noted and treatment proved effective in all cases. This paper also discusses the natural history, clinical effects, and current treatment for envenomations from these beautiful but dangerous venomous fish, which can cause poisoning exposures that are likely to be encountered by poison centers anywhere in the world. PMID- 2929131 TI - Rhododendron macrophyllum poisoning in a group of goats and sheep. PMID- 2929132 TI - Comments on diagnosis of intoxication due to taxus. PMID- 2929133 TI - Wide local excision of acanthomatous epulides in the dog. AB - Twenty-five dogs bearing acanthomatous epulides of the oral cavity underwent tumor resection by wide local excision. The surgical procedures included rostral mandibulectomy, removal of the mandibular body, premaxillectomy, and partial maxillectomy. Postoperative complications were rare, and local recurrence was not encountered in any dogs over periods of 1 to 6 1/2 years (median, 22 months). The authors conclude from the high incidence of local recurrence after simple excision through the tumor margins and the potential for malignant transformation after irradiation that wide surgical resection is the technique of choice for the management of acanthomatous epulis. PMID- 2929134 TI - The use of skin expansion to repair cosmetic defects in animals. AB - Skin expansion was used in three horses, one heifer, and one dog to aid in the repair of cosmetic defects. Skin expansion was produced by inserting an expandable silicone device subcutaneously and gradually inflating the device with saline. Skin expansion allowed skin to be mobilized and sutured over cosmetic defects without excessive tension. A successful outcome was achieved in four of the five cases reported here. In one animal, two attempts to create a pocket for a silicone prosthesis failed because the expanders ruptured. Complications included implant failure, wound dehiscence, and exposure of an expander. Skin expansion can be used to enable closure of skin defects in areas where skin tension usually precludes repair by local transposition. PMID- 2929135 TI - Significance of the Heineke-Mikulicz pyloroplasty in the treatment of gastric dilatation-volvulus. A prospective clinical study. AB - Twenty-six dogs with gastric dilatation-volvulus (GDV) were stabilized medically, followed by tube gastrostomy and gastropexy. In 13 dogs, a Heineke-Mikulicz pyloroplasty was also performed. Complications and recurrences were monitored during the immediate postoperative period and for 5 to 31 months thereafter. Barium gastrograms and contrast radiographs of the stomach were evaluated at week 1 and months 5 to 31. Significantly fewer dogs without pyloroplasty had complications during the immediate postoperative period. There were no differences in the long-term complication rates. Radiographic evaluations of the width of the pylorus, the size of the stomach, and the rate of gastric emptying showed no differences between dogs with and without pyloroplasty at any evaluation period. The Heineke-Mikulicz pyloroplasty increased the immediate postoperative complication rate after surgical fixation of the stomach for the treatment of GDV. It did not appear to influence the long-term outcome of the surgical treatment of this disease. The Heineke-Mikulicz pyloroplasty is not recommended in the treatment of GDV unless pyloric outflow obstruction can be demonstrated. PMID- 2929136 TI - Metoclopramide reversal of decreased gastrointestinal myoelectric and contractile activity in a model of canine postoperative ileus. AB - Postoperative ileus is characterized by decreased gastrointestinal myoelectric activity and motility. Metoclopramide was used to treat experimentally induced postoperative ileus in six dogs. Contractile activity was monitored by extraluminal strain gages on the pyloric antrum and proximal segment of the duodenum, and myoelectric activity was measured by recording bipolar electromyograms (EMGs) at the pyloric antrum, pyloric canal, proximal segment of the duodenum, proximal and distal parts of the jejunum, and ileum. Measurements were obtained from animals without ileus (baseline) and those with ileus that were either untreated or treated with metoclopramide. Adynamic ileus was induced by rubbing a 50 cm segment of jejunum with a dry sponge for 5 minutes and exposing the bowel to the air for 30 minutes. Treated dogs received metoclopramide (0.4 mg/kg 4 times daily [QID] intravenously [IV]), whereas untreated dogs received a saline placebo, starting 1 hour after celiotomy closure. Recordings were made for 26 hours after induction of ileus. The phases of the migrating myoelectric complex (MMC) were identified and motility index values were determined. During ileus, the MMC phase II duration was increased at the duodenum and phase III duration was decreased at the antrum, pylorus, duodenum, and proximal segment of the jejunum (p less than 0.05). Motility index values were decreased at the antrum and duodenum during ileus (p less than 0.05). Treatment with metoclopramide reversed the MMC phase III inhibition at the antrum and pylorus, and partially reversed the inhibition at the duodenum and jejunum (p less than 0.05). Motility index values were restored to preoperative baseline values with metoclopramide treatment (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2929137 TI - Occlusion of the external carotid and maxillary arteries in the horse to prevent hemorrhage from guttural pouch mycosis. AB - Balloon-tipped catheters were used to occlude the external carotid artery and its branches in nine horses with hemorrhage caused by guttural pouch mycosis. The internal carotid artery on the affected side was occluded simultaneously in four horses and had been occluded previously in two others. In three horses, a single balloon-tipped catheter was inserted in the external carotid artery beneath the floor of the guttural pouch and its tip was advanced blindly into distal branches. In one horse, the superficial temporal artery was occluded briefly during surgery by a balloon-tipped catheter so a catheter inserted into the external carotid artery could be diverted into the maxillary artery. In the other five horses, the external carotid artery was occluded proximally and the maxillary artery was occluded immediately caudal to the alar canal by a balloon tipped catheter inserted into the major palatine artery. Serious postoperative hemorrhage did not occur in eight horses, but one horse that had a single balloon tipped catheter inserted into the external carotid artery had profuse hemorrhage 11 days after surgery and was euthanatized. One horse was euthanatized because of persistent dysphagia. The only complication related to use of balloon catheters was a mild incisional infection in one horse. It was concluded that the external carotid and maxillary arteries must be occluded on both sides of the eroded segment to prevent hemorrhage from normograde and retrograde flow. PMID- 2929138 TI - Surgical treatment of sand colic. Results in 40 horses. AB - A retrospective study of 40 horses that underwent surgical treatment for sand colic was performed. Three horses were euthanatized and one died during surgery. Of the 36 horses that recovered from anesthesia, five died before discharge from the hospital and seven died after discharge. Twenty-four horses survived at least 12 months. Sand impaction of the right dorsal colon was present in 26 horses. In addition to sand impaction, 10 horses also had colonic displacement or volvulus. PMID- 2929140 TI - Scientific presentation abstracts. American College of Veterinary Surgeons. 24th annual meeting. February 1989. PMID- 2929139 TI - Long-term follow-up of partial limb amputation in 13 horses. AB - Thirteen cases of partial limb amputation in horses were reviewed. Nine horses (69%) survived 18 to 111 months (mean, 41 months). Four unsuccessfully treated horses were euthanatized within 21 days of surgery. The horses' ages at amputation were 4 to 13 years (mean, 7.3 years). There was no predilection for the left or right limb nor for fore or hind limb involvement. Osteomyelitis in six horses (46%) was the most common cause for amputation. Severe, open, comminuted fractures of the third metacarpal bone that were impossible to stabilize by any currently available technique in four horses (31%) were the second most common cause for amputation. One gelding was salvaged because of his sentimental value, two horses were used as breeding stallions, and six were broodmares. One stallion lived 30 months, completed two breeding seasons, and started a third. The other stallion began breeding, but became sterile. Three of the mares have produced five foals. One mare died while in foal. One mare aborted near-term twin fetuses and died of uterine hemorrhage. One mare aborted twice before the femoral head ligament on the contralateral limb ruptured, and she was euthanatized. PMID- 2929141 TI - Intraoperative irradiation of 16 spontaneously occurring canine neoplasms. AB - Sixteen dogs with malignant neoplasms were treated with intraoperative radiation therapy after surgical debulking. Fractionated external beam radiation therapy was given postoperatively to 11 dogs. Healing of surgical incisions was uncomplicated in 14 dogs. When the ureters or urinary bladder were included in the irradiation field, they became stenotic and fibrotic. Urinary incontinence and secondary renal injury were common. Local tumor control was poor regardless of site or tumor type. PMID- 2929143 TI - The National Nursing Home Survey: 1985 summary for the United States. PMID- 2929142 TI - A preliminary comparison of lidocaine and xylazine as epidural analgesics in ponies. AB - Xylazine (0.35 mg/kg) or lidocaine (0.35 mg/kg) was injected into the epidural space of six ponies to compare their effectiveness as epidural analgesics. Each pony received both treatments at 1 week intervals with the order of treatments randomized. Xylazine produced analgesia of significantly longer duration (247 +/- 58 minutes) than that produced by an equal dose of lidocaine (135 +/- 22 minutes). Mild transient ataxia of no clinical significance developed in all ponies with both treatments. Spinal cords were removed from two ponies and examined histologically. No discernible pathologic changes were noted. PMID- 2929144 TI - Remarriages and subsequent divorces. PMID- 2929145 TI - Children of divorce. PMID- 2929146 TI - [Treatment of severely depressed hematopoiesis]. AB - Severe inhibition of haematopoiesis is a serious disease from the prognostic aspect. The authors evaluated a group of 26 patients of whom one survived for more than five years. The mean life span is 154 days. The most frequent cause of death are infectious complications, in particular septicaemia. Investigation of the aetiology of the disease was negative in 46% of the cases, in the remainder drugs were suspected most frequently, in particular antibiotics. It is very important to prevent the development of secondary inhibition of haematopoiesis, in particular by careful indication of myelotoxic drugs. In case of necessity, these drugs should be administered for a short time, in the lowest effective doses with check-ups of the haemogram. Hope for affected patients in future is transplantation of bone marrow and the early administration of antilymphocytic globulin. PMID- 2929147 TI - [Long-term study of disorders of heart rhythm in patients with chronic diseases of the respiratory system]. AB - The authors investigated the incidence of arrhythmias by the method of continuous recording of ECG tracings according to Holter in 16 patients with chronic respiratory diseases three times in the course of two years. The incidence of arrhythmias was very frequent, more serious disorders (class 3 or a higher class according to Lown's classification) were very rare. The authors provided evidence of a great variability in the incidence of arrhythmias in the same patients during different periods of investigation. They did not reveal a relationship between the incidence of arrhythmias and the degree of functional affection of the lungs, the severity of hypoxaemia and the drop of the maximum aerobic capacity of the lungs. They did not find a relationship between the incidence of arrhythmias and the pressure in the pulmonary artery, or the size of the right or left ventricle or the thickness of their wall. The authors do not consider the finding of arrhythmias in patients with chronic lung disease an unequivocally serious finding, as reported sometimes in the literature. PMID- 2929148 TI - [Changes in blood pressure in mild forms of hypertension after long-term physical training]. AB - The authors submit the results of a long-term study of the treatment of mild hypertension by physical training. Its advantage, as compared with medicamentous treatment, is the physiological effect on the organism, its financially unpretentious character, and if the population is seriously informed, its wide application. The authors found in general a poor approach to physical activity, in particular among young people due to lack of information on the importance of physical activity. They conclude that physical training is the method of choice in the treatment of mild forms of hypertension. The blood pressure attained normal levels after this treatment in liminal hypertonics as well as hypertonics stage I. PMID- 2929149 TI - [The somatotropic hormone and liver diseases]. AB - The authors examined in 1980-1988 a total of 114 patients aged 18-87 years suffering from chronic liver disease. In all these patients they examined in addition to RIA assay of somatotropic hormone (STH) bilirubin and basic liver enzymes, using common methods. They recorded a significant increase of STH in patients with cirrhosis of the liver. In the other diagnostic groups the STH levels were within the reference zone or at its upper borderline. The authors analyzed also STH levels in relation to diabetes and drew attention to its frequent occurrence (type II) in patients with cirrhosis of the liver. The authors analyze also STH variations in the course of ageing. PMID- 2929150 TI - [Relation of HLA antigens and the length of survival in patients with acute leukemia]. AB - The authors examined and evaluated by statistical methods 80 patients with acute leukaemia (AL). The group comprised 56 myeloid (AML) and 24 lymphocytic (ALL) leukaemias. In AL and AML no significant relations with transplantation antigens were detected. In ALL an increased frequency of HLA-B5 was found which was statistically significant (Fischer's test pc = 0.046). In women, as compared with men, an increased frequency of antigens A28, B17 was found and a reduction of HLA B35. The values were not statistically significant. The authors sought relationships between the presence or absence of some HLA antigens (A2, A3, A10, B12) and the survival period of the patients. The results were not unequivocal. The findings were evaluated with regard to data reported in the literature. PMID- 2929151 TI - [Pachydermoperiostosis--development of bone changes 25 years after disease onset]. AB - Pachydermoperiostosis-hyperostosis generalisata cum pachydermia is considered a sex-linked hereditary pathological disposition of the mesenchyme with a favourable course of the dominant form; it is, however, progressively malignant in the recessive type of heredity. As a rule men affected. The author describes the case of a patient where the disease was diagnosed 25 years previously. PMID- 2929152 TI - [Clinical evaluation of granulocyte concentrates in the treatment of malignant disorders of hematopoiesis]. AB - The authors evaluate in a retrospective, non-randomized two-year study the action of 57 granulocyte concentrates from a Fenwal CS 3000 separator in 12 patients used for induction therapy of acute leukaemia, malignant lymphoma and agranulocytosis, as compared with a control group of 18 patients without concentrates. The indication for selection was granulocytopenia of less than 0.5.10(9)/l, temperatures resistant to antibiotics for more than 48 hours, mainly gram-negative sepsis and a severe localized infection. A significant reduction of febrile days was achieved, to 6.08 as compared with 12.44 (p less than 0.001) along with cure of the infection. Survival, evaluated on the 21st day of the investigation in the treated group 66.6%, as compared with 61.1%, and the percentage of complete remissions 58% as compared with 55.56%, were not statistically significant (p greater than 0.05). The mean one-hour rise of granulocytes by 0.37 x 10(9)/l in the recipients had no clinical impact. With the exception of one patient a relationship was observed between the favourable action of transfusions and the trend of recovery of the patient's granulopoiesis and the onset of remission of the disease. Minor pyretic and allergic reactions occurred in three patients (5.2%). PMID- 2929153 TI - [Benign clear-cell tumor of the lung (a case report)]. PMID- 2929154 TI - [Multiple lung hamartomas (a case report)]. PMID- 2929155 TI - [Kaposi's sarcoma with visceral involvement and a fulminant course]. PMID- 2929156 TI - [Familial colon cancer]. AB - 5 families with autosomal dominant inherited colonic cancer were analyzed with reference to the characteristics of familial colonic cancer: 45% out of 54 family members had colorectal carcinomas, with a mean of 4.5 affected members per family. The mean age on diagnosis of colonic cancer was 43.9 years. 50% of the colorectal carcinomas were located in the right colon; 11 out of 14 carcinomas were Dukes C, with a predominance of poorly differentiated adenocarcinomas and mucin-producing cancers. 22% had synchronous cancers and 13% developed metachronous cancers. Cancer at another location was found in 8.7% of cases. Prospective screening of relatives (siblings, children) revealed a colonic neoplasm in 3 out of 6 asymptomatic subjects. The typical characteristics of familial colonic cancers were demonstrable in our patients. The elucidation of an exact family history in all patients with colorectal carcinoma and a strategy of meticulous surveillance are absolutely necessary for the diagnosis and management of this inherited trait. PMID- 2929157 TI - [Side effects of adjuvant therapies of breast cancer: their significance for the patient]. AB - In a retrospective survey we interviewed 53 patients with respect to side effects of adjuvant therapy for breast cancer. All of them had undergone modified mastectomy and were randomly assigned to either chemotherapy, irradiation or a combination of both. Standardized questionnaires concerning the side effects and semi-structured, focusing counseling talks were the methods used in questioning the patients. Patients named significantly more side effects of severe and extreme intensity with chemotherapy, and especially in the group given combination therapy, where chemo- and radiotherapy could be directly compared by the patient. The experience was particularly threatening when several side effects occurred simultaneously. Different psychological aspects and visualisation of systemic and local side effects are discussed with respect to the patient's ability to cope with adjuvant therapy. Consequences for routine care are: continuous explanatory talks about side effects throughout the whole process, muscle relaxation and interdisciplinary cooperation. PMID- 2929158 TI - [Effect of early diagnosis on the prognosis of metastatic breast cancer]. AB - Between 1980 and 1986 676 patients with primary breast cancer were operated on with curative intent at the Department of Surgery of the Hanusch Hospital in Vienna. Of these 133 developed recurrences. The patients were closely followed up at our outpatient clinic. We have retrospectively analysed this patient collective to evaluate the impact of routine technical and chemical-pathological follow-up programmes on the detection rate of subclinical distant metastases and on improvement of prognosis. There was no difference in the outcome with respect to survival after recurrence and to overall survival between patients with early detection of recurrence at an asymptomatic stage, who received general antitumor therapy immediately and a second group where therapy was initiated only upon clinical manifestation of metastasis. The results are discussed in relationship to screening costs. We would like to emphasize the importance of follow-up programmes in the timely detection of local recurrence and also of cancer of the contralateral breast, as well as benefitting the psychological aspect of the doctor-patient relationship. PMID- 2929160 TI - Depositions: preparing for battle. Interview by Don Harper Mills. PMID- 2929159 TI - Self-poisoning with drugs. AB - A retrospective review was made of all patients with the diagnosis of drug ingestion or overdose seen in an urban community hospital over 30 months. There were 133 episodes involving 129 patients. Of these, 104 (78%) were hospitalized, including 96 at the study hospital. Fifty-three patients (55%) were initially admitted to the intensive care unit, and 57 (59%) were cared for in the psychiatry unit at some time during their course. One patient died, and 21 others (15%) suffered adverse consequences, including airway compromise requiring intubation, aspiration, seizures, cardiopulmonary arrest, and significant arrhythmias. The treatment rendered was supportive only, with no patient requiring hemodialysis or hemoperfusion. Multiple drugs were involved in 31% of the overdoses. The most common agents were benzodiazepines (32%), tricyclic antidepressants (24%), and acetaminophen (20%). A history of drug ingestion was obtained in 94% of patients. Based on subsequent drug level and drug screen testing, the history was judged accurate in 71% and inaccurate in 29%. The problems confronting hospitals that care for relatively few overdose patients but in a consistent pattern are discussed. PMID- 2929161 TI - [Comparative cinematographic, endoscopic and functional analytic studies of the pre- and postoperative evaluation of the severity of the tracheobronchial collapse syndrome]. AB - Sixty eight adults of both sexes (33 patients with clinically and endoscopically verified tracheobronchial collapse; 35 persons without disease of the central airways) underwent continuous cinetracheographic studies of the wall-movements of the central airways during various respiratory maneuvers. The insufflation of powdered tantalum for a better outlining of the contours of the central airways was preferably done in local anaesthesia via an orotracheally inserted catheter. Studies of wall-movement were made in recumbent position during forced breathing and violent coughing in various obliquities using a 35 mm-camera. The percentage of diameter-shortening during expiration (forced breathing; violent coughing) in relation to the inspiratory diameter during the same breathing-maneuver was measured in 4 or 3 projections respectively at 5 localities (cervical trachea; thoracic outlet; thoracic trachea 1 cm above the bifurcation; right and left main bronchus, 1 cm distant from bifurcation). Out of maximally 17 single numerical values per examination the highest single value was selected as the so-called "maximal relative diameter-shortening" - independent of locality and projection. In healthy persons the mean value amounts to 22.4 +/- 15.44% (means +/- SD) during forced breathing and to 75.5 +/- 11.72% during violent coughing. Patients with a tracheobronchial collapse differ from healthy persons, the former having a value of 100% during violent coughing. This is equivalent to a brief contact of the membranous part to the ventral circumference of the trachea (total cough collapse) at least at one locality in one projection. Out of a number of 28 patients 17 cases (group H) revealed a normal "maximal relative diameter shortening" of 29.7 +/- 21.57% during forced breathing. In addition to the total cough-collapse 11 patients (group F) exhibited an increased prolapse-tendency of the membranous part during forced breathing, too; the mean value of the "maximal relative diameter-shortening" amounted to 80.5 +/- 16.15%. Pathological shortening-values are mainly measured at the intrathoracic trachea in the lateral and both oblique projections. The cinetracheobronchographic examination should be used in patients with endoscopic signs of a tracheobronchial collapse-syndrome if an operative procedure with tautening is taken into consideration. In the case of mere clinical suspicion of the presence of a collapse-syndrome the assessment of the wall-motility is non-invasively possible by means of cinetracheography without a contrast-agent.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2929162 TI - [The measurement of bronchial mucociliary clearance using 99mTc for evaluating the success of the salt water cure]. AB - We found a highly significant improvement in the pulmonary mucociliary clearance in the peripheral region of the lungs four weeks after saline spring treatment. We examined the possibility of applying the saccharin sky-blue test for evaluating the success of spa treatment. PMID- 2929163 TI - [Malignant blue nevus]. AB - In a 6-year-old boy, we found a malignant blue nevus with metastases of the lymph nodes. After surgical therapy under melanoma conditions, he was treated with interferon. Up to now (2 years after therapy), the follow-up examinations have been negative. PMID- 2929164 TI - Why's, wherefore's, and what to do about soaring health plan rates. PMID- 2929165 TI - The President addresses some chief concerns. PMID- 2929166 TI - Insuring a healthy medical liability insurance system. PMID- 2929167 TI - Carbon monoxide poisoning in indoor ice skating arenas. PMID- 2929168 TI - Physician's guide to the Natural Death Act. PMID- 2929169 TI - [Light reflection rheography and invasive measurement of venous pressure in the standing exercise test]. AB - The peripheral venous hemodynamics of the lower limbs was simultaneously and repeatedly investigated by means of light-reflection-rheography and peripheral venous pressure measurement with healthy volunteers (total = 40 lower limbs). Two different kinds of exercise were used (knee-bends and tiptoe-stands). The measurements showed highly significant differences (p less than 0.001) between knee-bends and tiptoe-stands not only for all three hemodynamic parameters of non invasive light-reflection-rheography (maximum reflection difference, refilling time, half-refilling time) but also for all three parameters of the invasive venous pressure measurement (venous pressure difference, refilling time, half refilling time). There are statistically significant correlations of medium importance (p less than 0.01) between refilling times/half-refilling times of both investigative methods by knee-bends and tiptoe-stands. But there is no significant correlation between light-reflection difference and venous pressure difference. As exercise programme of light-reflection-rheography or invasive peripheral venous pressure measurement the most suitable is the programme in standing position, which represents the maximum hydrostatic load on the insufficient veins and reveals the pathologic condition of venous outflow better than the exercise programme in sitting position. PMID- 2929170 TI - [Advertising gifts]. PMID- 2929171 TI - [Prevention of infection in teflon prostheses for dialysis access. Experiences with a resorbable combined collagen-antibiotic system]. AB - 40 patients with renal insufficiency and chronic hemodialysis received a E-PTFE prosthesis as vascular access either at the upper or lower extremity. The efficacy of prophylaxis of infection through application of a local aminoglycosid, administered as a resorbable collagen-antibiotic-sponge, was studied in two different groups. All patients had a high risk of infection. The use of the collagen-gentamycin-sponge was effective in preventing an infection of the vascular graft. Systemic side effects were not registrated in spite of the reduced renal function. Further studies are necessary to evaluate the efficacy of the collagen-gentamycin-sponge in preventing vascular prosthesis infection in high risk patients. PMID- 2929173 TI - The effect of six months intensive physical training on the circulation in the legs of patients with intermittend claudication. AB - Out of 94 patients with intermittent claudication 65 completed a program of 6 months intensive physical training. Every 2 months the blood pressure indices at the thigh and at the ankle and the blood flow in the calf were measured at rest, after 5 min arterial occlusion and after exercise of the calf muscles until claudication. First the reproducibility of the blood pressure indices and the blood flow values was established. An increase of 15 in the pressure indices was considered to be substantial. An increase of 6.0 ml/100 ml/min in flow values was considered a substantial change. The blood pressure indices did not increase significantly during the training period, the blood flow values increased significantly. On the basis of the non-invasive tests no reliable statement can be made as to the expected result of the training. PMID- 2929172 TI - [Indications-related use of stockings--measuring venous pump function]. AB - In 48 patients (16 healthy persons, 16 patients with venous incompetence and 16 patients with phlebographic proved status after thrombosis) the effect of medical compression stockings of different compression pressure (Sigvaris Thrombo, Sigvaris 503, Sigvaris 504) on venous pumping function was studied by foot volumetry. In patients with varicosis and preexistent reduced pumping function the expelled volume in average ascended from 13.0 to 16.23 (+25%, Sigvaris 503), respectifly to 16.52 (+27%, Sigvaris 504) (p less than 0.05 Wilcox and Wilcoxon test). In patients in status after deep leg vein thrombosis with very reduced pumping function it came to an increase of expelled volume from 8.48 to 11.08 (+31%, Sigvaris 503) and to 12.55 (+48%, Sigvaris 504) (p less than 0.01). The hospital stocking Sigvaris Thrombo did not really improve the venous pumping function. So for the first time the common prescription of medical compression stockings class II in patients with varicosis and in mild cases of chronic venous incompetence and of stockings class III in patients in status after deep leg vein thrombosis is justified by measurement. PMID- 2929174 TI - Changes of walking distance in patients with intermittent claudication during six months intensive physical training. AB - Patients with intermittent claudication were treated with six months intensive physical training. They were instructed to walk with a speed of 6 km/h until they got complaints and then to rest for some time. This sequence was repeated until men below 65 years had walked 2 km. Men above the age of 65 years and women had to walk 1.5 km. This training session was performed 3 times a day. Every two months the claudication distances in a corridor and on a treadmill were measured. Out of 95 patients 65 completed the training. In 38 patients (59%) there was no substantial change in walking distance. Fourteen patients (22%) doubled their walking distance, seven (11%) could walk more than 1000 m, but their complaints remained. Six (9%) could walk more than 1000 m without claudication pain. Most patients gained their result during the last 2 months of the program. After the training 48% of the patients were satisfied with their walking distance. PMID- 2929175 TI - [Imitation of acute, deep venous thrombosis of the lower leg by a ruptured Baker's cyst]. AB - In case of a swollen leg, differential diagnosis includes deep venous thrombosis. After having ruled out a thrombosis by venography, other causes have to be sought. We report a case where massive swelling of the lower leg was due to the arthrographically proven rupture of a Bakers' Cyst. Had more emphasis been put on recording the patients history, time loss and diagnostic procedures could have been minimized. PMID- 2929176 TI - Femoral-tibial bypass for limb salvage. AB - From 1967 to 1982, 305 femoral tibial bypasses were performed. Of these 180 (59%) were performed on limb salvage indication. A reversed autogenous saphenous vein was used in 134 instances, among 46 vein substitutes there were 15 vein allografts, 13 human umbilical cord vein grafts, 12 PTFE grafts and six dacron grafts. Hospital mortality was six patients. An additional 37 patients died during the follow-up period. The patency rates for saphenous vein bypass grafts were 62.5%, 48%, and 25% at one, five, and ten years, respectively, and 33% and 25% at one and five years, respectively, for the vascular substitutes. The mean +/- SD follow-up time was 62.27 +/- 5.7 months. During the early postoperative period 23 legs (12.7%) had to be amputated. During the follow-up period an additional 14 legs (7.8%) were lost giving a limb salvage rate of 79.5%. PMID- 2929177 TI - [Improved quality of life through the prevention of cardiovascular diseases?]. PMID- 2929178 TI - Immunologic equinox--between two centuries. PMID- 2929179 TI - [Proceedings of the 4th joint meeting of the Society of Neuropathology of East germany and the Association of Polish Neuropathologists. 11-14 May 1988, Gorlitz. Abstracts]. PMID- 2929180 TI - [Leigh disease. Morphology and clinical aspects]. AB - Morphologico-topographic differences, especially with regard to size and distribution of foci, as well as equalities of the histomorphological pattern are shown in an infantile and in a juvenile case of Leigh's disease. Almost identical microscopic findings in the area of the olives in the medulla oblongata seem to be of special importance. The typical symptoms at the beginning of the disease with predominance to muscular hypotonia and the bulbar paralytic final stage might at least enable a tentative diagnosis even without evidence to the basic enzymatic defect, mostly in pyruvate metabolism, and changes in mitochondria in muscles and the central nervous system. The morphological investigation should especially include the medulla oblongata. PMID- 2929181 TI - Ultrastructure of cortical synapses in the brain of schizophrenics. AB - The autopsy was performed in 225 cases of chronic schizophrenia. In 44 cases examination of the brain by light microscope revealed changes typical of Alzheimer's disease. The increased risk for the development of Alzheimer's disease in chronic schizophrenia is pointed out. In 8 schizophrenics where death occurred suddenly and unexpectedly electronmicroscopy of brain was carried out. Clusters of a great number of synaptic vesicles were found in presynaptic knobs in the brain cortex of the schizophrenics but not in the controls; the postmortal origin and/or fixation artefact origin of the clusters were excluded. The possible "immunologic dependent" clustering of synaptic vesicles is discussed. The new "modul concept" in the structure of the brain cortex is used to make the role of synapses in the mental process more clear. PMID- 2929182 TI - [A simple method for the isolation of GFAP and its use for the study of brain tumors]. AB - A simple method is described in this paper for the production of a polyclonal antiserum against GFAP. The antiserum was tested on 212 primary brain tumours which had been selected from biopsy and autopsy material of the Institute of Pathological Anatomy at the Medical Academy of Erfurt, GDR. 52 of 81 astrocytomas (64%) and 26 of 47 glioblastomas (55%) gave GFAP-positive results. GFAP-negative responses were primarily recorded from tumours with severe anaplasia. GFAP was found in all 22 ependymomas tested. Epithelioid ependymomas, however, exhibited lower immunological reactions than tanycytic variants. Isomorphic oligodendrogliomas, meningiomas, medulloblastomas, and brain metastases of carcinomas were GFAP-negative. The possibility is discussed in some detail of falsely negative results on account of too little biopsy material or insufficient fixation of tumour tissue. PMID- 2929183 TI - [The morphology of HIV encephalopathy]. AB - Reported in this paper are postmortem findings recorded from the central nervous system of 51 HIV carriers, among them 43 with clinically manifest AIDS. Opportunistic infections and tumours were established in 24 cases, including toxoplasmosis, cytomegaly, progressive multifocal leucoencephalopathy, and lymphomas. Findings obtained from 5 patients were restricted to unspecific alterations. No pathological findings at all were recordable from 8 HIV carriers without AIDS. So-called subacute microglial encephalitis (SME) was detected in 26 cases. SME was found to provide for the morphological substrate of genuine HIV encephalopathy. It was characterised by occurrence of mononuclear and even multinucleated cells which were macrophages and obviously served as virus carriers. Multinucleated cells are pathognomonic of HIV encephalopathy. No unambiguous evidence has so far been produced to primary invasion of neurons or glial cells by HI viruses. PMID- 2929185 TI - [Craniopharyngioma in a fetus]. AB - Intrauterine sonography reveals pathological enlargement of the head and an abnormal intracranial mass in a fetus (25th week of gestation). Birth induction results in a stillborn female child (weight 1,590 g; length 35 cm; head circumference 32 cm). The supratentorial space is almost totally occupied by a craniopharyngioma, measuring 8 cm in diameter. PMID- 2929184 TI - [Homologous cerebral atrophy and ischemic insults in progeria adultorum]. AB - Neuropathological findings obtained from a female patient, 49 years of age, with progeria adultorum (Werner's syndrome) are described in this paper. Vascular sclerosis with multiple ischaemic infarctions, cerebral atrophy, and vascular myelopathy were the most strongly pronounced CNS findings. Also recorded were severe lipofuscin depositions from the cortex, dentate nucleus, and olivae as well as amylaceous bodies in the insula of Reil and the hippocampus. Neurofibrillary tangles or plaques were not recordable. The central nervous system proved somewhat comparable to other organs, in that mesenchymal regressive changes were the main features. PMID- 2929186 TI - [Proceedings of the 32d annual meeting of the German Society of Neuropathology and Neuroanatomy. October 1987, Marburg. Abstracts]. PMID- 2929187 TI - Investigation on monoclonal antibodies against two serovars of the icterohaemorrhagiae serogroup of Leptospira. AB - By means of the cell fusion technique, two hybridoma cell lines, V-1 and H2-1 have been obtained. V-1 cells secrete monoclonal antibody against serovars icterohaemorrhagiae and dakota. The H2-1 cell line secretes serovar-specific monoclonal antibody against serovar H2. These monoclonal antibodies have been successfully used in serovar-typing of leptospires isolated in China. The results of identification of leptospires by using monoclonal antibodies showed total coincidence with that by the traditional cross agglutinin absorption test and factor antiserum method. It was confirmed by using monoclonal antibody that the serological agglutination totally paralleled with animal protection. On the basis of the study, a concept was proposed that the agglutination in vitro and the protection in vivo are different manifestations in different reaction systems from the same antibody (antibodies) stimulated by a component(s) of the surface antigen of leptospires. PMID- 2929188 TI - Ability of smooth and rough variants of Mycobacterium avium and M. intracellulare to multiply and survive intracellularly: role of C-mycosides. AB - A spontaneous rough (Rg) mutant of M. avium ATCC 15769 was mutagenized using N methyl-N-nitro-nitrosoguanidine (MNNG). Out of 54 clones initially chosen on the basis of their morphological appearance on the 7H11 agar, seven Rg clones were selected on the basis of their response to current biochemical tests, and were later characterized for their cell wall amphiphilic contents (analysis of loosely bound surface lipids for mycosides, peptidolipids, phospholipids, and mycolic acids by thin layer chromatography, and fatty acids by gas chromatography), and ability to grow intracellularly inside J-774 macrophages. A parallel study was also performed on a previously reported Rg mutant of M. intracellulare serovar 20 (W.W. Barrow and P.J. Brennan, J. Bact. 150 (1982) 381-384) which lacked the ability to synthesize mycosides C (MYC-). The results obtained were compared to parental smooth (Sm) colony-types of the respective M. avium-intracellulare strains. Our results showed that neither the ninhydrin-reacting lipids (probably peptidolipids) nor the glycopeptidolipids (mycosides C) were primary factors responsible for the intracellular survival and multiplication of these bacteria. Ultrastructural studies showed that although the polysaccharide-rich outer wall layer (POL) in case of MYC- Rg strain was not uniformly distributed and contained blebs, these bacteria formed the characteristic electron-transparent zone (ETZ) upon phagocytes by macrophages. Furthermore, the multiplication of MYC- Rg strain inside macrophages did not result in intracellular selection of MYC+ bacteria, nor in Rg to Sm transition. PMID- 2929189 TI - Antigenic analysis of Vibrio cholerate O1 by crossed immunoelectrophoresis. AB - Antigens from Vibrio cholerae O1 were analyzed by crossed immunoelectrophoresis (CIE) using sera from immunized rabbits. Thirty different anode-migrating antigens were detected in sonicated antigen preparations of V. cholerae. These antigens were numbered in order to establish a reference precipitation pattern. Antigen no. 30 was identified as the lipopolysaccharide (LPS) antigen, because it reacted with (i) periodic acid-Schiff (PAS) reagent and (ii) the affinity purified anti-LPS antibodies. Treatment with proteinase K demonstrated that most of the precipitation lines were due to proteins, a part of which were localised at the cell surface. The major outer membrane protein was found to be closely associated with the precipitation line due to the LPS (antigen no. 30). The antigenicity and immunogenicity of V. cholerae cells killed by different methods (merthiolate, heat, phenol, formalin) were examined. As determined by CIE, killing with merthiolate preserved most of the major components of V. cholerae. Heat, phenol and formalin altered the antigenic mosaic of V. cholerae. These results suggested that CIE can be used to analyze several aspects of V. cholerae antigens. PMID- 2929190 TI - [Microbial colonization of carious progression stages in the dentin of human teeth--a controlled therapeutic study]. AB - In a controlled clinical trial the microflora of the cavity floor of 70 primary lower second molars with deep carious lesions were determined after caries excavation. The teeth were extracted and pulpal status was evaluated after 16 months of microbial control to determine the etiopathogenic role of germs for carious progression in dentine. 67% of the primary molars were free from pulpal inflammations. Soft carious dentine were significantly higher infected than the clinically acceptable hard dentine. Only in 40% of the cavity floors the microorganisms were eliminated. In the infected teeth basophilic microorganisms were found in causality to pulps without inflammations; acidogenic streptococci and lactobacilli were involved in pulpal inflammations. Results indicate that the latter genera of microorganisms are of etiological significance for carious progression in dentine. PMID- 2929191 TI - Antibodies against toxic shock syndrome toxin no. 1 (TSST-1) in Poland. AB - A total of 174 sera from healthy Polish individuals of different age groups were tested for TSST-1 antibody by the micro-ELISA method. Over 90% of sera contained the antibody with titres equal to above 1:10(2), even in children and adolescents. The data suggest that the majority of the Polish population acquires TSST-1-antibody during early childhood, whereas a small portion of the population seems to remain anti-TSST-1-negative. PMID- 2929192 TI - Enhancement of neutrophil adherence to Toxocara canis larvae by the C3 component of complement and IgG antibodies. AB - In the present study, the binding human neutrophils to Toxocara canis larvae was examined in vitro. It was found that IgG and/or the C3 component of complement were able to enhance the attachment of the cells to the parasites. This was associated with the generation of strong chemiluminescence reactions. Despite the binding of the cells, the larvae were able to escape and to maintain their infectivity. This was apparent, since the parasites could survive and migrate into different organs including the brain after having been inoculated into mice. PMID- 2929193 TI - Duck hepatitis B virus: cloning and subcloning of the viral genome. AB - In the course of studies on the biology of hepadnavirus infections, duck hepatitis B virus (DHBV) DNA was isolated from the serum of a German Pekin duck. Viral DNA was cloned in E. coli using pBR 322 DNA as a vector. The cloned DHBV DNA F 1-6 was characterised by restriction enzyme analyses. DHBV DNA F 1-6 was subcloned in both orientations in plasmid pSP 65 to produce strand-specific RNA probes. These probes specifically identified asymmetrically replicating nascent minus-strand DHBV DNA species or plus-strand viral RNA transcripts. PMID- 2929194 TI - Prevalence of Borrelia burgdorferi in Ixodes ricinus ticks in Berlin (West). AB - In 1986, 1711 nymphal and adult Ixodes ricinus orginating from Berlin (West) forests were examined individually or in pools of up to 10 ticks for the presence of Borrelia burgdorferi, the etiologic agent of Lyme borreliosis. Detection of borreliae was carried out by means of a culture method using modified Barbour Stoenner-Kelly-Medium (BSK II). Tick populations from 14 out of 15 locations contained positive specimens. The calculated minimal infection rate of pooled ticks was 2.5% in nymphs (n = 1365), 10.2% in females (n = 59), and 5.3% in males (n = 114). Among those ticks examined individually, none of the nymphs (n = 49) proved to be positive but B. burgdorferi was isolated from 8.2% of the females (n = 73) and 7.8% of the males (n = 51). Fifty-five out of 56 isolates were identified as B. burgdorferi by means of an indirect immunofluorescence test (IFT) using monoclonal antibody H 5332. From these results B. burgdorferi must be considered as being present in the Berlin area. PMID- 2929195 TI - Flotation of mastitis pathogens with cream from subclinically infected quarters. Prospects for developing a cream-rising test for detecting mastitis caused by major mastitis pathogens. AB - Bacterial isolates, originating from 36 subclinically infected quarter milk samples, were labelled with 75Se and checked for cream-rising at various temperatures in a system analogous to the ABR test ("Abortus Bang Ringprobe"; the cream-rising test based on stained brucella organisms for detection of brucellosis). Diagnostic specificity and sensitivity were analyzed in experiments where labelled bacterial isolates were mixed with a number of quarter milk samples with known bacteriological status as well as samples from healthy control quarters. Creaming at 37 degrees C resulted in specific "recognization" as the bacterial isolates showed preferential flotation in the milk samples from which they had been isolated as well as is milk samples harbouring the same bacterial species. At lower creaming temperatures, the specificity was lost since all the isolates became concentrated in the cream phase irrespective of the milk sample. When comparing the specific recognization by cream of the respective bacteria, bacterial species vary: The prospects for developing diagnostic cream-rising tests for Streptococcus agalactiae, Staphylococcus aureus and Escherichia coli seems promising, but less so for coagulase-negative staphylococci, Streptococcus dysgalactiae, and Streptococcus uberis. The mechanism behind the cream-rising of labelled bacteria at 37 degrees C seems to lie in specific fat globule membrane bound immunity of IgA type. Therefore the milk fat globules from chronically infected quarters function as absorbents for the respective isolates. Flotation of bacteria with cream indicates an in vivo mechanism enabling bacteria to invade the upper parts of milk ducts within the udder.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2929196 TI - On the suitability of the MTT-assay for the evaluation of mitogenic lymphocyte blastogenesis in swine. AB - Using swine peripheral blood lymphocytes, we examined the suitability of a colorimetric tetrazolium (MTT) reduction test for the evaluation of mitogenic lymphoblastogenesis in comparison to radiolabelling methods. In our study, we did not find a correlation between the 3H-thymidine- or 14C-thymidine uptake into DNA and the mitochondrial MTT cleavage activity, comparable to that formerly demonstrated for mouse cytotoxic T cells and for sheep peripheral blood lymphocytes. With the MTT assay, mitogen-driven lymphocyte activation was scarcely assessable, whereas a clear mitogenic response could be observed using radiolabelling methods. The results show that the MTT cleavage activity reflects quite a different state of cellular function than the DNA synthesis and that the evaluation of this activity is not suited to determining lymphocyte activation in swine as a measure of mitogenic response. PMID- 2929197 TI - Analysis of some swine influenza H1N1 viruses by oligonucleotide fingerprinting. AB - The genome of the swine influenza H1N1 virus Sweden/83 was compared to other H1N1 viruses by oligonucleotide fingerprinting. This analysis revealed that Sweden/83 is identical to the Danish strain Sjaelland/82 and is thus to be placed in the group of "US viruses". On the other hand, the Danish strain Als/82 was found to be different, i.e., related to the Belgium/79 strain which is a representative of the "European viruses". The results of the present genomic analysis confirm the previous findings of relationships between the above strains. PMID- 2929198 TI - Changes in plasma kallikrein and PGF2 alfa concentrations during circulatory shock. Studies with superior mesenteric artery occlusion in anesthetized dogs. AB - Among the mediators for development of endotoxic shock, plasma kallikrein and prostanoids have been suggested to play an important role. The role of kallikrein and PGF2 alfa in circulatory shock of intestinal origin was investigated in anesthetized dogs by measuring inactive and active kallikreins and PGF2 alpha in superior mesenteric vein, right ventricle and aorta during shock induced by occlusion of the superior mesenteric artery. After removal of the clamp in dogs subjected to occlusion for 1 hour, the mean arterial blood pressure fell rapidly within 5 min and gradually increased over the next 60 min, with return to the control values. The plasma concentrations of PGF2 alfa in superior mesenteric vein, right ventricle and aorta increased three- to fivefold within 5 min of reperfusion. Thereafter the PGF2 alfa levels fell, so that at 60 min after declamping they did not significantly differ from the control values. No significant changes were observed in the levels of inactive and active kallikreins. The results suggest that PGF2 alfa released by intestinal tissues may contribute to the development of shock caused by intestinal ischemia. PMID- 2929199 TI - Angiographic runoff patterns in patients undergoing lower limb revascularization. AB - Intraoperative postreconstruction serial angiography was performed in 194 patients undergoing lower-limb revascularization (206 limbs), in order to analyze the atherosclerotic involvement of the lower leg and foot arteries. Occlusion of two or three leg vessels was found in 71% of the diabetic patients, and in 52% of the non-diabetics. The peroneal artery was less frequently affected than the other leg arteries. Severe involvement of the foot arteries was commonly observed in patients with only one or no patent leg vessel. The posterior foot arch was less commonly affected than the anterior. Complete visualization of the lower leg and foot arteries is suggested to be important for adequate evaluation of the distal vascular runoff. Pedal runoff may have prognostic significance in femoropopliteal as well as femorodistal bypass surgery. PMID- 2929200 TI - Gastric banding in the treatment of morbid obesity. Factors influencing immediate and long-term results. AB - Gastric banding for morbid obesity was performed on 73 patients between April 1983 and December 1986. Early complications occurred in 16% and late complications in 15% of the cases. A second operation was performed on 12 patients, with removal of the band in 11 (15%). Initial weight loss was rapid. Re examination of 67 patients indicated that this initial loss was followed by a time-related weight gain. Weight reduction occurred as a fairly constant proportion of preoperative weight, irrespective of the degree of obesity. Weight loss to body mass index less than or equal to 30 seems to be a realistic expectation only for moderately overweight patients, not for the hyperobese. Older patients had least weight loss. The data suggest that dietary restrictions will still be needed after gastric banding. PMID- 2929201 TI - Second follow-up study of mucosal changes in the gastric remnant after resection for peptic ulcer disease. AB - Second follow-up 36-37, 26-27 and 15-18 years after gastric resection for peptic ulcer disease was performed for 72 patients who in the first screening five years earlier had severe atrophic gastritis and/or intestinal metaplasia in the gastric remnant mucosa. Of the 72 patients 60 were still alive. The death certificates revealed no gastric stump carcinomas among the 12 deceased patients. Neither were any cases of gastric stump carcinoma found among the 38 endoscopically screened patients. Severe atrophic gastritis, which was present in 37 patients in 1982-83, had regressed in 14 cases (p less than 0.01) and proceeded in one case. The extent of intestinal metaplasia had increased in 11 cases and decreased in five cases (p = 0.149, NS). Dysplasia, which was not seen five years ago, was now detected in four cases (10.5%). There was an association between dysplasia and incomplete intestinal metaplasia in three cases. Although these mucosal changes may be premalignant it is not possible to be categorical about the prognosis. Thus, endoscopic screening of all patients whose stomach has been resected for peptic ulcer disease cannot be recommended. Endoscopy, however, is always indicated when gastric symptoms appear in a patient with history of gastric resection. PMID- 2929203 TI - Histologic features of gastric cancer in relation to patterns of spread. AB - The modes for growth and spread of gastric cancer were investigated in a surgical series of 115 cases--88 of early disease, and 27 involving the muscular layer. In addition, 93 autopsy cases with advanced disease were examined in order to analyze metastatic spread. In cancers of differentiated type in the mucosal layer, changes in histologic features towards the undifferentiated type were observed in the deeper layers, but no histologic transformation was seen in cancers of undifferentiated type. At autopsy distant metastases were common in cases with primary tumor of differentiated type, whereas peritoneal dissemination predominated when the primary lesion was undifferentiated. From the clinical standpoint, follow-up and recommendations to the patient should focus mainly on risk of peritoneal dissemination when adenocarcinoma of the stomach is of undifferentiated type, whereas metastases to distant organs should be taken into consideration if the malignancy is histologically differentiated. PMID- 2929202 TI - Trial of pectin-enriched muffins in patients with severe dumping syndrome after gastric resection. Observations on symptoms and gastric emptying pattern. AB - Pectin is known to delay gastric emptying and alleviate dumping symptoms when ingested with hyperosmolar, glucose-containing meals. As the treatment of dumping syndrome includes frequent, small dry meals, the effect of pectin ingested in muffins was tested in five patients with severe, intractable dumping syndrome after gastric resection. Ingestion of 99mTc-DTPA-labelled muffins containing 5 g pectin did not alleviate dumping symptoms or delay gastric emptying compared with muffins without pectin. Pectin does not seem to be beneficial as a supplement in the conventional dietary management of post-gastrectomy dumping. PMID- 2929204 TI - Late radiation injuries of the small intestine--management and outcome. AB - A series of 86 patients with late radiation-induced lesions, mainly stricture, of the small bowel is reviewed. The median interval from radiotherapy to manifestation of enteropathy was 2 (1/4 to 43) years. Progression of the lesions necessitated further treatment in 35 of the 70 patients who survived the initial attack. Bowel resection was followed by leakage from 12% of ileo-ileal and ileo colic anastomoses. Mortality was 34% from the enteropathy and 8% from coexisting damage to the rectum or urinary tract. Factors significantly influencing mortality were pre-irradiation laparotomy, emergency surgery, and surgery to deal with a segment of irradiated intestine left in situ at initial operation. Age, stage of primary malignancy and coexisting rectal or urinary tract lesions did not significantly influence the outcome. After a median of 10 years' observation the outcome was classified as favourable in only 28% of cases, while 30% had slight to moderate symptoms or had died of unrelated causes. When surgery is required for radiation-related lesions of the small intestine, the aim should be a one-stage definitive procedure, as management of subsequently progressing lesions is associated with substantially increased mortality. PMID- 2929206 TI - Papillary thyroid cancer with unusually aggressive behaviour. Case report. AB - A 22-year-old woman underwent thyroid lobectomy for papillary carcinoma (follicular variant). Local recurrences 4 and 7 months later, with vascular invasion and extrathyroid spread, required extensive surgery and radiotherapy. Ipsilateral lobectomy with near-total or total contralateral lobectomy is advocated for treatment of papillary thyroid cancer. PMID- 2929205 TI - Volvulus of the colon. A review of 93 cases and current aspects of treatment. AB - Ninety-three patients, comprising a consecutive, population-based series, were treated for volvulus of the colon between 1970 and 1985. The male:female ratio was 3.3:1 among the patients with volvulus of the sigmoid colon and 1:3.7 among those with caecal volvulus (p less than 0.001). Of the 60 patients with sigmoid volvulus, nine (15%) died. Elective surgery was performed in 13 of these 60 cases, without postoperative mortality. Previous volvulus attack(s) had occurred in 22 of the 60. Of the nine patients who underwent only detorsion at laparotomy, four had recurrence. Of the 33 patients with caecal volvulus, 31 underwent emergency laparotomy, and in seven of them the outcome was fatal. Of the nine patients who survived pexis operations, three had recurrence of volvulus. The results indicate that immediate laparotomy can be hazardous in patients with colonic volvulus. Semi-emergency resection after tube decompression, when the patient is in optimal condition and with preoperatively prepared bowel, is probably preferable. PMID- 2929207 TI - Embryonal rhabdomyosarcoma of the oesophagus. Case report. AB - In an 81-year-old man fibreoptic endoscopy and contrast radiography revealed an obstructive malignant tumour of the oesophagus. The patient survived only 2 months after diagnosis. Light and electron microscopy and immunohistopathologic studies confirmed the diagnosis of embryonal rhabdomyosarcoma. PMID- 2929208 TI - An isolated aneurysm of the internal iliac artery simulating lumbar disc herniation. Case report. AB - A case is presented of an isolated aneurysm of the internal iliac artery in a patient with signs of lumbar disc herniation. Isolated aneurysms of the internal iliac artery are rare and they may present with symptoms of compression of adjacent structures or hemorrhage. PMID- 2929209 TI - Hematemesis due to fistula between aorta and esophagus and later to fistula between left common carotid artery and esophagus. Case report. AB - A case of massive hematemesis due to an aortoesophageal fistula is presented. The diagnosis was made intraoperatively. The patient died 39 days postoperatively of an additional, previously unidentified fistula between the left common carotid artery and the esophagus. This fistula combination does not seem to have been reported previously. PMID- 2929210 TI - Villous adenoma of the duodenum. Case report. AB - Two rare cases of villous adenoma of the duodenum are described. Obstructive jaundice was the presenting clinical feature. Histologically the tumour was benign in both cases. Local excision was performed. One year later both patients were free from recurrence, but one was treated for gastric adenocarcinoma after 2 years. The literature is reviewed. PMID- 2929211 TI - Rupture of the spleen following endoscopic retrograde cholangiopancreatography (ERCP). Case report. AB - In a 46-year-old woman endoscopic retrograde cholangiopancreatography, performed to evaluate acute pancreatitis, was followed by splenic rupture, probably due to manipulation of the patient on the X-ray table in combination with the endoscopic procedure. The excised spleen was histologically normal. Various causes of splenic rupture are discussed. PMID- 2929212 TI - Ischaemic pancolitis: a serious complication of chemotherapy in a previously irradiated patient. Case report. AB - A 47-year-old man underwent orchidectomy and radiotherapy for seminoma. Six years later he received chemotherapy for oesophageal carcinoma. After the second cycle gangrenous pancolitis developed, necessitating total colectomy. The pancolitis presumably resulted from the earlier irradiation and current chemotherapy. This complication has particularly grave implications in oesophageal malignancy, since colon is often used as oesophageal substitute. PMID- 2929213 TI - Biological response modifiers in treatment of cancer with special reference to GI cancer: present status and future aspects. 1988 Oncology Symposium. Goteborg, Sweden, March 13-17. PMID- 2929214 TI - Monoclonal antibodies (MAb 17-1A) for the treatment of patients with metastatic colorectal carcinomas. PMID- 2929216 TI - Silver-binding nucleoli and nucleolar organizer regions in fine needle aspiration cytology of the breast. AB - Silver staining was used to demonstrate nucleoli and nucleolar organizer regions (NORs) in cytopreparations from breast fine needle aspiration (FNA) biopsies, with the resulting black dots being a combination of silver-binding nucleoli and dispersed NORs. Discrete black dots in 200 nuclei were manually counted in 25 silver-stained biopsies; the cytologic diagnoses were made on routine Papanicolaou-stained cytopreparations from the same aspirates. Although malignant breast lesions showed higher counts than did benign breast disease, an overlap of one malignant and three benign lesions occurred. Therefore, the method cannot be recommended for reliably discriminating between malignant and benign routine breast specimens obtained by FNA; it may have some value in assessing tumor behavior. PMID- 2929215 TI - Fine needle aspiration cytology of parotid sarcoidosis. AB - Granulomatous lesions of the salivary gland are rare; as such, there have been few reports of the cytologic features of granulomatous sialadenitis in general, and salivary gland sarcoidosis in particular. A case of systemic sarcoidosis involving both parotid glands, diagnosed initially by fine needle aspiration (FNA) cytology, is presented. The specific cytologic features included histiocytes of both epithelioid and giant multinucleated types, without background necrosis. The FNA cytologic differential diagnosis of bilateral parotitis is discussed. PMID- 2929217 TI - Fine needle aspiration cytology of radiation-induced changes in nonneoplastic breast lesions. Possible pitfalls in cytodiagnosis. AB - The range of radiation-induced changes in fine needle aspiration (FNA) smears of the breast is described. In 41 of more than 800 patients who underwent breast conserving treatment, a palpable breast lesion developed, and FNA was performed. In six cases, a recurrent carcinoma was present. In the remaining cases, three patterns of nonneoplastic lesions could be discerned: epithelial atypia (14 cases), fat necrosis (10 cases) and poorly cellular smears without epithelial atypia or fat necrosis (13 cases). It is important to be familiar with the patterns of radiation-induced epithelial atypia, since such atypia may lead to a misdiagnosis of recurrent carcinoma. These atypical cells may show impressive anisocytosis and anisonucleosis; however, the nuclear/cytoplasmic ratio remains normal and an admixture of bipolar cells is present. Cell dissociation and necrotic cell debris, as often seen in breast cancer smears, were never encountered in FNA smears from radiated nonneoplastic breasts. PMID- 2929218 TI - Fine needle aspiration cytology of adenosis tumor of the breast. With immunocytochemical and ultrastructural observations. AB - The fine needle aspiration (FNA) findings of multinodular sclerosing adenosis forming a discrete lesion (so-called "adenosis tumor") of the breast are presented. The findings in this case and a review of the literature indicate that adenosis tumor is an unusual breast lesion that can clinically and histologically be confused with breast carcinoma, especially at the time of frozen section. FNA biopsy demonstrated uniform groups of ductal cells, stromal fragments and many stripped bipolar nuclei, which led to a correct diagnosis of a benign proliferative breast lesion, but not to a specific diagnosis of adenosis tumor. Immunoperoxidase staining for muscle actin demonstrated positive staining of many bipolar spindle-shaped cells, indicative of myoepithelial cells. Immunohistochemical studies on the resected specimen demonstrated actin positivity of myoepithelial cells and intact linear staining of type IV collagen around the ductules. Ultrastructural examination demonstrated ductal cells with surrounding myoepithelial cells resting on a delicate basal lamina, with surrounding bundles of collagen in the interstitial space. This appears to be the first FNA cytologic description of this unusual breast tumor and the first immunohistochemical and ultrastructural characterization of this lesion. FNA cytologic examination may more clearly identify the benign nature of the breast mass than frozen section. PMID- 2929219 TI - Adenoma of the nipple. Cytopathologic features. AB - The cytologic appearances of two examples of adenoma of the nipple are described. The cellular samples from both lesions contained large numbers of epithelial cells, which were present both singly and in numerous clusters. The uniform nuclei contained finely distributed chromatin and inconspicuous nucleoli. Some of the cells varied in size and shape; a few had hyperchromatic nuclei. Small amounts of cellular debris, inflammatory cells and hemosiderophages were also present. Adenoma of the nipple can usually be distinguished cytologically from other lesions that may involve the nipple, such as Paget's disease, adenocarcinoma, fibrocystic disease, mammary duct ectasia, intraductal papilloma and chronic subareolar abscess; the cellular features of fibroadenoma, however, overlap those of adenoma and may cause diagnostic confusion. The increasing use of cellular samples obtained from breast lesions underscores the importance of recognizing this uncommon neoplasm and its cytologic manifestations. Adenoma of the nipple can be treated successfully by limited resection, and preoperative recognition will obviate unnecessary extensive surgery. PMID- 2929220 TI - Carcinoid tumor metastatic to breast diagnosed by fine needle aspiration. Case report and literature review. AB - Fine needle aspiration (FNA) biopsy was used to study a mass in the left breast in a patient with a previous history of an ileal carcinoid tumor and later lymph node metastases who presented with bilateral palpable breast masses. The FNA specimens showed the lesion to be a carcinoid tumor. The metastatic nature of the lesion was proven by positive restaining of FNA smears by both the Sevier-Munger technique (demonstrating abundant argyrophilic cytoplasmic granules) and the Fontana-Masson method (showing argentaffin cytoplasmic granules). The distinction between primary and metastatic carcinoid tumors of the breast is discussed, as is their origin and their differentiation from other malignancies of the breast. PMID- 2929221 TI - High-grade mucoepidermoid carcinoma of the breast. Fine needle aspiration cytology and clinicopathologic study of a case. AB - A primary high-grade mucoepidermoid carcinoma of the breast was evaluated preoperatively by fine needle aspiration (FNA) cytology in a 72-year-old woman. The smears showed a mixed pattern consisting of clusters of poorly differentiated squamous cells, keratinized squamous cells and vacuolated mucin-secreting cells. The subsequent mastectomy specimen showed a tumor with the features of a high grade mucoepidermoid carcinoma. Electron microscopy confirmed the diagnosis, reflecting the epidermoid and glandular differentiation of the tumor. The course was rapidly fatal, and the patient died a few months after presentation. A review of the literature indicated that mucoepidermoid carcinoma of the breast is a very rare neoplasm; the FNA cytologic features described in this report may constitute a basis to preoperatively recognize this tumor. PMID- 2929222 TI - Pure squamous carcinoma of the breast. Report of a case diagnosed by aspiration cytology. AB - A case of pure squamous carcinoma of the breast diagnosed by needle aspiration cytology is presented. The three conditions required for that diagnosis were fulfilled: (1) an absence of elements other than malignant epidermoid cells, (2) the independence of the lesion from adjacent dermal structures, and (3) the exclusion of other squamous carcinomas in the patient. Other well-documented cases of this entity are reviewed. PMID- 2929223 TI - Intraobserver and interobserver variability in the quality assessment of cervical smears. AB - Intraobserver and interobserver variability in assessing the quality of cervical smears, as measured by the presence or absence of endocervical columnar cells and squamous metaplastic cells, was evaluated. In total, 180 cervical smears representing the most important cytologic diagnoses were anonymously rescreened twice by 19 observers with an interval of six months. An absence of endocervical columnar cells was proven to correlate with a high percentage of false-negative diagnoses. Intraobserver agreement on the presence or absence of endocervical columnar cells was 85.7% between the two screenings. A predictive value of 57.7% was found for a negative scoring (absence of these cells) while the predictive value of a positive scoring (presence of endocervical cells) was 87.3%. Of the observer scorings, 83.9% concurred with the final diagnosis; there was no significant correlation between that concurrence and the number of years of experience in cytopathology of the observer. For squamous and squamous metaplastic cells in the cervical smear the predictive value of a negative scoring (absence) was only 20.6%. Compared to the final diagnosis, 69.5% of these scorings matched. A significant and relatively high correlation with the experience of the observer was found for the scoring for the presence of metaplastic cells. Even though the predictive values of these quality scorings were relatively low a significantly higher risk for false diagnoses was established when negative scorings were given. It is therefore advisable to have smears with negative scorings for endocervical columnar cells and squamous metaplastic cells always rescreened by another observer. PMID- 2929224 TI - Immunocytochemical demonstration of Langerhans' cells in smears and pellets of exfoliated cells from human exocervices. AB - Immunocytochemical staining with OKT6 monoclonal antibody and S-100 protein antiserum was used to reveal Langerhans' cells in smears and/or pellets of exfoliated cells from uterine cervices (normal and with squamous carcinoma). Immunoreactive Langerhans' cells were found exclusively in smears and pellets of cervices with squamous carcinoma. Langerhans' cells, which appear as rounded cells, showed a peripheral ring of intense fluorescence with OKT6 antibody whereas the entire cell stained with S-100 protein antiserum. The presence of Langerhans' cells among cells exfoliated from exocervical squamous carcinoma can be explained by the increased density of these cells in tissue with neoplastic changes. PMID- 2929225 TI - Fine needle aspiration cytology of metastatic lymphoepithelioma. A case report. AB - A case is presented of lymphoepithelioma (undifferentiated nasopharyngeal carcinoma) metastatic to the cervical lymph nodes in a 12-year-old boy for whom material was obtained by fine needle aspiration (FNA) for the primary diagnosis as well as for ancillary studies. Papanicolaou-stained smears demonstrated the characteristic cytopathologic features of Regaud-type lymphoepithelioma; the diagnosis was substantiated by immunocytochemical and electron microscopic studies. This report discusses the reliability and rapidity of FNA in definitively diagnosing undifferentiated metastatic malignancies as well as providing superior material for ancillary studies demanded by lesions with complicated and difficult differential diagnoses. PMID- 2929226 TI - Inflammatory pseudotumor of the liver. Report of the fine needle aspiration cytologic findings in a case initially misdiagnosed as malignant. AB - The fine needle aspiration (FNA) cytologic features are described in a case of inflammatory pseudotumor of the liver (xanthogranuloma), a disease generally regarded as of unknown etiology. The initial FNA findings were those of an acute exudative process, with atypical biliary duct epithelium and hepatocytes. These were interpreted as verifying the radiologic impression of a malignancy. Histologic study of subsequently resected nodules revealed the true nature of the case. As the lesion evolved, granulomatous inflammation supervened, characterized by numerous foamy histiocytes and lesser populations of plasma cells and lymphocytes. Numerous gram-positive cocci were readily demonstrated, suggesting that the lesion was an unusual tissue response to an intrahepatic bacterial infection. The lesion eventually resolved with prolonged antibiotic therapy. PMID- 2929227 TI - Fine needle aspiration cytodiagnosis of an unusual parotid mass. PMID- 2929228 TI - Microbiologic classification of cervicovaginal flora in Papanicolaou smears. PMID- 2929229 TI - Cervicofacial actinomycosis: diagnosis by fine needle aspiration cytology. PMID- 2929230 TI - Aseptic knee effusion with Loa loa microfilariae in the articular fluid. PMID- 2929232 TI - Identification of Campylobacter-like organisms in gastric brushings. PMID- 2929231 TI - Identification of Giardia lamblia in peritoneal fluid of trauma patients. PMID- 2929233 TI - Carpet beetle larval hairs in a sputum cytology specimen. PMID- 2929234 TI - Assessing adrenocortical activity by determining levels of urinary free cortisol and urinary 6 beta-hydroxycortisol. AB - A comparative study of urinary free cortisol and urinary 6 beta-hydroxycortisol levels as a diagnostic test for hypercortisolemic states was carried out by measuring the excretion in 24-h specimens from 289 apparently healthy subjects and 10 Cushing patients. The diurnal variations of both variables were examined in normal subjects and subjects with altered adrenal activities. Two of the 289 apparently normal subjects had high values of urinary free cortisol; one had a high, the other a normal 6 beta-hydroxycortisol level; they were later diagnosed as having Cushing's syndrome and infertility, respectively. Three other subjects had high values of the urinary variables, but during 5 years of follow-up did not show any clinical evidence of hypercortisolism. The two urinary variables gave no false-negative results in the Cushing patients. The diurnal variation revealed that levels of 6 beta-hydroxycortisol change in parallel with those of free cortisol in normal subjects and in subjects with altered adrenal activities. However, the ratio of 6 beta-hydroxycortisol to free cortisol during the diurnal variation varied from low values when free cortisol levels were high to high values when free cortisol levels were low. In normal subjects, 1 mg of dexamethasone taken orally at 23.00 h completely suppressed the levels of both variables on the following day. It is concluded that urinary 6 beta hydroxycortisol is correlated to urinary free cortisol so that measurement of urinary 6 beta-hydroxycortisol levels can be used as a diagnostic test for hypercortisolism in a way comparable to the method using urinary free cortisol. PMID- 2929235 TI - Serum prolactin in uraemia: correlations between bioactivity and activity in two immunoassays. AB - The clinical significance of hyperprolactinaemia in uraemic patients is uncertain and discrepancies between immunoactivity and biological activity of serum hPRL have been reported. We have modified the Nb2 cell bioassay to improve specificity for hPRL and used this assay to measure hPRL bioactivity in sera from 26 uraemic patients and 40 control subjects. Seventeen patients were receiving regular haemodialysis and 9 continuous ambulatory peritoneal dialysis. Levels of hPRL bioactivity were compared with hPRL immunoactivity measured by RIA (PRL-RIA) and by immunoradiometric assay (PRL-IRMA). Serum hPRL levels measured by all three assays were significantly elevated in uraemic patients compared with control subjects (P less than 0.001). The immunoradiometric method gave significantly lower results than RIA in control subjects but not in uraemic patients (P less than 0.05). There was no significant difference in mean ratio of hPRL bioactivity to PRL-RIA between patients and control subjects (1.18 +/- 0.05 vs 1.11 +/- 0.03, mean +/- SEM). The ratio of hPRL bioactivity to PRL-IRMA was slightly decreased in uraemic patients compared with controls (P = 0.05). Serum hPRL bioactivity was closely correlated with immunoactivity in both immunoassays (r greater than or equal to 0.96) in patients and controls. These results confirm that elevated serum hPRL levels in uraemic patients represent biologically active hormone which may contribute to hypogonadism. PMID- 2929236 TI - Effect of hypophysectomy on the growth and development of the sheep adrenal gland: a morphometric study. AB - We have investigated the effect of gestational age and fetal hypophysectomy on the growth and development of the adrenal gland of the fetal sheep. The area of the fetal sheep adrenal medulla increased significantly (P less than 0.05) from 3.21 +/- 0.42 mm2 at 90-107 days to 6.09 +/- 0.26 mm2 at 120-126 days of gestation and there was a further significant increase (P less than 0.05) in the newborn period to 9.48 +/- 0.85 mm2. The adrenomedullary area of the hypophysectomised fetal sheep (7.47 +/- 1.10 mm2) was not significantly different from that of the fetal sheep at 140-146 days of gestation or from that of the newborn lamb. The ratio of the area of the adrenal occupied by the cells which contained adrenaline (adrenaline zone) to the area of the adrenal occupied by the cells which contained noradrenaline (noradrenaline zone) was unchanged between 90 days of gestation and 12 days after birth. After hypophysectomy, the ratio of the adrenaline to noradrenaline zone was not significantly different from that in the adrenal medulla of the 140-146 days fetal sheep and the 10-12 days newborn lamb. PMID- 2929237 TI - Endocrine disturbances in suprasellar germinomas. AB - The authors have investigated hypothalamic-pituitary function in 8 patients (aged 9-27 years) with surgically and histologically proven suprasellar germinomas. Diabetes insipidus was found in 7 patients. All the patients had hypogonadism and hypocortisolism as judged by dynamic endocrine testing. Hypothyroidism was found in 6. Moreover, growth hormone secretion, as assessed by insulin-induced hypoglycemia, was defective in all patients. Comparison of results of insulin induced hypoglycemia testing and stimulation tests by CRH and GHRH suggested that all patients had a primary suprahypophyseal lesion rather than a primary pituitary defect. The authors conclude that suprasellar germinomas, although uncommon, should be included in the differential diagnosis of juvenile suprasellar tumours and in cases suggestive of idiopathic diabetes insipidus, even if neuroradiological investigation fails to demonstrate a discrete tumour. PMID- 2929239 TI - Central effect of the enkephalin analogue FK-33824 on vasopressin secretion in conscious sheep. AB - The role of opioids in the regulation of arginine vasopressin release from the posterior pituitary is a subject of controversy. In the present study, we examined the effects of central administration of met-enkephalin, leu-enkephalin, the enkephalin analogue FK-33824, and the opiate antagonist naloxone, and the effects of systemic administration of met-enkephalin and FK-33824 on AVP secretion in conscious normal sheep. Intracerebroventricular infusion of FK-33824 significantly increased the plasma concentration of immunoreactive AVP in a dose dependent manner, but met-enkephalin, leu-enkephalin and naloxone failed to change plasma concentration of AVP. Intravenous infusion of met-enkephalin and FK 33824 also failed to change plasma concentration of AVP. The opiate antagonist naloxone given both centrally and systemically attenuated the increase in plasma concentration of AVP induced by FK-33824. We conclude that basal AVP release is stimulated by central administration of FK-33824. PMID- 2929238 TI - Rat adipose tissue adenosine sensitivity and adenosine content after subcutaneous administration of N6-(phenylisopropyl)adenosine. AB - Injections of N6-(phenylisopropyl)adenosine, a nonmetabolizable adenosine A1 receptor agonist, desensitized rat adipocytes to the drug in 20 h. Lipolysis stimulated by 2 mumol/l DL-isoproterenol was inhibited markedly less by N6 (phenylisopropyl)adenosine in adipocytes isolated from treated than control animals (P less than 0.01). Glucose uptake was more responsive to N6 (phenylisopropyl)adenosine in adipocytes from control than treated animals (P less than 0.02). Adenosine content was the same in adipose tissue of control and treated animals. The number of adenosine binding sites was not significantly lower in treated compared with control animals (1580 +/- 279 and 1988 +/- 575 fmol/mg protein; mean +/- SEM). There was no change in receptor affinity (Kd = 10 nmol/l in both groups). There was no decrease in the amounts of the inhibitory guanine nucleotide binding protein (Gi) alpha subunits as studied by pertussis toxin catalyzed ADP-ribosylation. It is concluded that desensitization to N6 (phenylisopropyl)adenosine can be observed without changes in the adenosine receptor status or decrease in the amount of inhibitory guanine nucleotide binding protein and that adipose tissue adenosine content is not changed by the agonist treatment. PMID- 2929240 TI - Influence of diet on the development of antral gastrin-like immunoreactivity in the stomach of rats. AB - The effects of individual food constituents on antral gastrin-like immunoreactivity concentrations were studied in young rats. Rats aged 7 to 20 days were given only rat breast milk and then weaned by various nutrients (regular laboratory chow, protein (ovalbumin)-, fat- or carbohydrate (starch) rich food). Rats receiving rat breast milk only until 27 days of age were also studied. In rats on regular laboratory chow, antral gastrin-like immunoreactivity increased and reached adult levels on day 25. In rats on ovalbumin, fat-rich food or starch, it increased on day 23 but dropped thereafter. The increment by laboratory chow was higher than that by the individual nutrients. No increase was observed during milk feeding alone. Gel filtration of antral gastrin-like immunoreactivity from 25-day-old rats on laboratory chow or three essential nutrients showed the same results. PMID- 2929241 TI - Program of plenary sessions and advance abstracts of short communications. 33. Symposium Deutsche Gesellschaft fur Endokrinologie. Karlsruhe, February, 22-25, 1989. PMID- 2929242 TI - A professional opportunity: writing for the AANA Journal. PMID- 2929243 TI - Clinical implications of intraoperative continuous mixed venous oxygen saturation monitoring. AB - Mixed venous oxygen saturation (SvO2) is an indirect indicator of cardiac output. Twenty-nine patients undergoing aortic reconstructive surgery were studied to determine whether a sustained 5% or greater change in SvO2 (1) is associated with a similar change in cardiac output, and (2) results in a change in therapy during anesthetic management of the patients. Pulmonary artery cannulation with a fiberoptic oximeter catheter was used for continuous monitoring of SvO2 values in addition to usual hemodynamic parameters. Hemodynamic measurements and therapeutic manipulations were recorded when SvO2 changed by 5% or more for a period exceeding 60 seconds. Any sustained change of 5% or more in SvO2 was plotted against change in cardiac output. The relationship between 5% or greater changes in SvO2 and the initiation of therapeutic interventions was also tested. Results showed a highly significant relationship between changes in SvO2 and initiation of therapeutic intervention. This data suggests that the likelihood of a therapeutic intervention in a patient with a change in SvO2 of 5% or greater is highly significant. The relationship between change in SvO2 and cardiac output was also significant. This suggests that changes in SvO2 are reflective of changes in cardiac output, and thus, the hemodynamic status of the patient. PMID- 2929245 TI - Mechanical circulatory support: the intra-aortic balloon pump (IABP) PMID- 2929244 TI - Laryngospasm-induced pulmonary edema. AB - Laryngospasm is one of the more common forms of airway obstruction encountered by an anesthetist. Therapy usually is straightforward, with resolution of the obstruction normally occurring within minutes. In some cases, however, the patient's vigorous inspiratory efforts may lead to a rapidly deteriorating form of pulmonary edema. Two cases are presented that are quite typical of the development of this complication. The etiology, recognition and management of this form of non-cardiac pulmonary edema is discussed. PMID- 2929246 TI - Use of a student support group to reduce student stress in a nurse anesthesia program. AB - Stress in nurse anesthesia programs may be excessive at times, especially in new students. While some degree of stress is necessary to motivate learning, excessive or prolonged stress can interfere with the normal learning process, thereby prolonging a student's clinical and academic progress. In the extreme, excessive stress may even preclude a student's successful completion of the educational program. Active faculty intervention through a student support group is advocated as a method for controlling stress levels and facilitating student learning. The positive effects of such intervention also increase the overall productivity of a program and better prepare nurse anesthesia students for their future careers. PMID- 2929248 TI - High frequency ventilation 20 years of endeavour reviewed: final stress or departure to achievement. An international symposium. Munster, FRG, February 29 30, 1988. Proceedings. PMID- 2929247 TI - AANA Journal course: advanced scientific concepts: update for nurse anesthetists- anesthesia for patients on anticholinesterase and antiepileptic drugs. AB - Patients with neurologic diseases who require surgery may present the anesthetist with special challenges related to their pharmacotherapy. It is well established that such therapy may alter these patients' otherwise normal response to anesthesia. There are many classes of drugs utilized and this AANA Journal course addresses the pharmacokinetic, pharmacodynamic, and anesthetic implications of anticholinesterase and antiepileptic drugs. PMID- 2929249 TI - High frequency ventilation 20 years of endeavour reviewed. Why an expert meeting now? PMID- 2929251 TI - Volume-controlled ventilation with superimposed high frequency ventilation during expiration in healthy and surfactant-depleted pig lungs. AB - In the healthy and surfactant-depleted lungs of five pigs the influence of different forms of high frequency ventilation superimposed on conventional mechanical ventilation during the expiratory phase of the ventilatory cycle (SHFVE) on gas exchange and cardiocirculatory parameters was investigated. Subsequently the effects of end-expiratory flushing (EF), i.e. cleaning the large airways and connecting tubes from the ventilator free from end-expiratory CO2, with a volume greater than the dead space of the large airways and connecting tubes was investigated. SHFVE and EF resulted in a significant improvement in CO2 elimination in both healthy and surfactant-depleted lungs. Furthermore, in stiff lungs, at a certain level of oxygenation and CO2 elimination, SHFVE produced the lowest peak and mean airway pressure without any additional depression of cardiocirculatory parameters. PMID- 2929250 TI - A comparison of ventilation strategies for the use of high-frequency oscillatory ventilation in the treatment of hyaline membrane disease. AB - To assess the efficacy of high frequency oscillatory ventilation (HFOV) in the management of infants with hyaline membrane disease (HMD), we compared two HFOV strategies with conventional positive pressure ventilation with positive end expiratory pressure (PPV) for 24 h in premature baboons (140 d gestation). Three out of 14 PPV, five out of five HFOV-E (begun at birth; 15 Hz; I:E 1:2), and none of 10 HFOV-L (begun after 3 h PPV; 10 Hz; I:E 1:2) were killed at 24 h for morphologic examination. Physiologic (Paw, Pa/AO2, IO2, B.P., pulse, blood gases) data on all animals in each group were assessed at each 3 h interval and over time. Intergroup differences in radiographs at 0 and 24 h and in morphology were quantitatively assessed by comparison with a panel of standards. All animals had radiographic HMD. Initial Paw was set higher with HFOV-E (16.8) than PPV or HFOV L (14.1, 14.1). PPV baboons required increasing Paw to maintain constant Pa/AO2. Six out of 14 PPV animals developed airleak and three out of three had morphologic HMD. In contrast Pa/AO2 was higher in both HFOV groups at lower Paw by 24 h. None of 15 HFOV animals developed airleak. HFOV-E lungs had dramatic differences in morphology with uniform saccular opening and decreased edema and hyaline membranes compared to PPV. HFOV-L had less dramatic effects because of lower Paw and delayed application. Early use of HFOV at a high Paw favorably alters the course of HMD. Unless closely monitored, this strategy results in lung overinflation which may adversely affect venous return and cardiac output. PMID- 2929252 TI - High frequency oscillation: paradigm of inhomogeneous alveolar ventilation. PMID- 2929253 TI - High frequency ventilation (oscillation) in a neonatal unit. PMID- 2929254 TI - Ventilatory strategy in catastrophic lung disease. Inversed ratio ventilation (IRV) and combined high frequency ventilation (CHFV). AB - In 105 patients with well-defined catastrophic lung disease, in whom conventional settings were unable to maintain life-sustaining gas exchange, the ventilatory strategy was changed from volume-controlled ventilation with an inspiratory expiratory ratio (I:E) of 1:2 and PEEP of 15-20 cm H2O to pressure-controlled inverse ratio ventilation with an I:E of 2:1, 3:1 or 4:1 and a set PEEP of 4-8 cm H2O. All patients were ventilated on a Servo 900 B or C ventilator, the primary goal being to decrease the FIO2 below 0.6 and the peak pressure to below 50 cm H2O, while maintaining a PaO2 of 8.00 kPa and a PaCO2 within 10% of the upper limit of normal. In 67 patients the intervention was successful and peak pressure could be reduced to a median of 44 cm H2O (range 37-50). FIO2 could be reduced to a median of 0.50 (range 0.40-0.60). The auto-PEEP effect of IRV increased to a median of 12 cm H2O (range 7-22). No consistent pattern of change in cardiac output was observed. Sixty patients survived more than 3 weeks and 48 were discharged from hospital. The 38 IRV "failures" were changed to pressure controlled ventilation with superimposed high frequency ventilation (CHFV). In 30 cases the FIO2 could be reduced to a median of 0.60 (range 0.50-0.60) and peak pressures to a median of 50 cm H2O (range 45-60). In 21 patients the PaCO2 increased. Auto-PEEP with CHFV had a median value of 15 cm H2O (range 10 25).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2929255 TI - Indications for combined high frequency ventilation in clinical use. AB - A retrospective study of 20 surgical intensive care unit patients is reported. They were ventilated with continuous positive pressure ventilation (CPPV) and then switched to combined high frequency ventilation (CHFV). To find why there were variable responses to CHFV, the data of 20 patients were retrospectively evaluated with respect to respiratory index (RI), compliance (C) and extravascular lung water (EVLW). The results suggest that the indication line for CHFV was a C value greater than 45 ml/cmH2O and an EVLW value greater than 15 ml/kg BW. PMID- 2929256 TI - Combined high frequency ventilation (CHFV). PMID- 2929257 TI - Interpretation of conventional measurement of gas exchange in high frequency ventilation (HFV). PMID- 2929258 TI - Pulmonary mechanics during high frequency ventilation. PMID- 2929259 TI - HFV and pulmonary physiology. AB - The major conclusion reached by this writer is that HFV can be considerably better than CMV in fluid-filled or collapsed lungs. However, the reason for success has nothing to do with unique molecular flow regimes for gas in the airways during HFV, but is the natural consequence of HFV permitting lung volume stability without as high peak pressures (as in CMV) following a "conventional" hyperinflation. If this lesson alone can be absorbed and used by all in the HFV field, this meeting will have been a success and the future of HFV will not look so dark after all. PMID- 2929261 TI - Gas exchange during high frequency ventilation. PMID- 2929260 TI - Pulmonary gas exchange in panting dogs: a model for high frequency ventilation. AB - Panting in animals can be expected to represent a naturally occurring physiological counterpart to today's techniques of mechanical high-frequency ventilation. To analyze the mechanisms underlying the gas exchange inefficiency during ventilation with high frequencies, steady-state pulmonary gas exchange was studied in seven conscious dogs (32 kg mean body weight) during panting elicited by mild thermal stress. The animals had a chronic tracheostomy and an exteriorized carotid artery loop and were exposed to 27.5 degrees C ambient temperature for 2 h (65% relative humidity). Open-circuit techniques were used and PO2 and PCO2 from the tracheostomy tube were continuously monitored by mass spectrometry using a special sample-hold phase-locked gas sampling technique. PO2 and PCO2 were determined in arterial blood collected from the carotid artery. During the exposure, the following variables of steady-state gas exchange were determined (means +/- SD): breathing frequency 313 +/- 19 min-1; tidal volume, 167 +/- 21 ml; total ventilation, 52 +/- 9 l.min-1; effective alveolar ventilation, 5.5 +/- 1.3 l.min-1; partial pressures (torr; a, arterial; E', end tidal): PaO2, 106.2 +/- 5.9; PaCO2, 27.2 +/- 3.9; (PE'-Pa)O2, 26.0 +/- 5.3; (Pa PE')CO2, 14.9 +/- 2.5. According to the conventional lung model, parallel-dead space ventilation (ventilation of unperfused lung regions) would account for about 55% of the alveolar ventilation and for 2/3 of the (PE'-Pa)O2 difference. However, the lack of an 'alveolar plateau' in the CO2 and O2 expirograms suggests that incomplete serial mixing in peripheral airways contributes to the enhanced gas exchange inefficiency during panting as reflected in the increased blood/gas differences for O2 and CO2. PMID- 2929262 TI - Physical characteristics of a jet in the airways. PMID- 2929264 TI - Resonance in the mechanical response of the respiratory system to high frequency jet ventilation. AB - Eight normal domestic pigs (Large White breed) of body weights 17 kg to 62 kg were subjected to high frequency jet ventilation (HFJV) at frequencies of 1 to 10 Hz (60-600 breaths/min). Six animals survived the study. The gain response curves and phase shift response curves obtained for these animals indicate that respiratory system resonance can be excited at HFJV frequencies. Post-mortem examinations of the nonsurvivors' lungs suggested pulmonary barotrauma. These findings and their clinical implications are discussed. PMID- 2929263 TI - Convective mixing mechanisms in high frequency intermittent jet ventilation. AB - A liquid flow visualization technique was used to identify the location of neutrally buoyant bead clouds injected into airway models during flows simulating high frequency intermittent jet ventilation (HFIJV) in neonatal lungs. The motions of these bead clouds show that the convective or bulk mixing that occurs during HFIJV is made up of two parts; a turbulent convective exchange with the atmosphere caused by the jet in the trachea and a streaming motion along the airways driven by an interaction between the jet and the expansion and contraction of the airways due to their compliance. These convective streaming motions combine with molecular diffusion to produce augmented diffusion which transports O2 and CO2 between the trachea and the peripheral alveoli. Optimizing HFIJV (as well as other forms of HFV) depends on maximizing these airway convective streaming flows which depend on many more lung and fluid mechanical parameters than are necessary to describe conventional mechanical ventilation. PMID- 2929265 TI - Gas movement during jet ventilation. AB - By examining flows in the expiratory limb of a bias flow circuit, it is possible to measure tidal, entrained and spilt volumes during jet ventilation. Using this method on a canine model, tidal volume fell and minute volume rose when the respiratory rate rose from 12 to 200 breaths/min. The changes were compatible with a convective model of gas movement. Entrained volume remained a constant fraction of tidal volume and spilt volume fell as a fraction of jet volume as respiratory rate increased. PMID- 2929266 TI - Gas flow distribution and tidal volume during distal high frequency jet ventilation in dogs. AB - During distal high frequency jet ventilation (HFJV) in anaesthetized healthy dogs gas flows were recorded at the proximal end of the open tracheal jet tube. Spirometer measurements of minute volumes with and without entrainment were made. During the inspiratory or insufflation period, leakage of jet gas (bypass) could occur depending on the ventilator setting. From the gas flow recordings and the spirometer measurements, jet-, entrainment- and bypass minute volumes were determined. From these the effective minute volume, that is the minute volume of fresh gas entering the lungs, was calculated, as well as tidal volume. The results show that entrainment volumes are relatively small in an open system of distal HFJV and that at the same time bypass can (nearly) completely eliminate the effect of entrainment on tidal volume. PMID- 2929267 TI - Lung surrogates. AB - In the development and evaluation of mechanical ventilation on the basis of high frequency oscillation, appropriate surrogates of the lung are important, because they allow the measurement and control of various parameters which are not accessible in animal models. Yet, criteria have to be established according to which results obtained with a surrogate may be assessed with a view to extrapolation to humans. Theoretical considerations and impedance measurements are used for this purpose. It is found that for each given frequency a model can be made which exhibits realistic properties. However, no uniformly valid surrogate in the entire frequency range of 10-50 Hz is available at present. PMID- 2929268 TI - Mobilization of mucus by airway oscillations. AB - The effects of high frequency asymmetric airway oscillations on mucus clearance were evaluated in excised tracheas of sheep, in an animal model of excessive mucus production, and in patients with bronchiectasis. Asymmetric high frequency ventilation (15 Hz) with expiratory biased flow profiles (expiratory peak-flow greater than inspiratory peak-flow) could move mucus droplets towards the pharynx in rigid and flexible tracheas by gas-liquid interaction. In rigid tracheas the mucus was transported towards the periphery of the model lung if the oscillations were inspiratory biased. In very collapsible tracheas, however, even inspiratory biased oscillations moved the mucus cephalad. Parameters influencing direction and speed of mucus are airflow profile, peak-flow, airway compliance and lung resistance. Gamma-camera studies showed that in anesthetized dogs radiolabeled artificial mucus followed the direction of the bias during high frequency ventilation. In five human volunteers with bronchiectasis and excessive secretions the asymmetric airway oscillations were superimposed during spontaneous breathing using a mouthpiece. Airway wall vibrations following the pressure swings of the oscillator could be observed. During forced expiration inward bulging of the posterior membranes of trachea and bronchi occurred at the negative pressure phase of the oscillations. This event was associated with increased appearance of sputum in the central airways. We conclude that high frequency ventilation with asymmetric flow profiles applied via tube or mouthpiece might be an effective future treatment of mucostasis. PMID- 2929269 TI - Multimodal evoked potentials in neuro-Behcet: a longitudinal study of two cases. AB - Two neuro-Behcet patients have been studied, over a period of several months, by means of peroneal and median somatosensory- (SEP), brainstem auditory- (BAEP), and visual- (VEP) evoked potentials. In both patients, peroneal SEP showed evidence of a pathological reduction in the central conduction velocity without a related deep sensation impairment, while VEP changes were consistent with the visual disorders. Conversely, BAEP and median SEP findings did not show disease related abnormalities. The observed anomalies were detectable irrespective of the clinical phase of the disease. Thus, evoked potential assessment is useful in providing objective evidence for evaluating and monitoring CNS damage in neuro Behcet's syndrome. PMID- 2929270 TI - Computed tomography (CT) in late infantile metachromatic leucodystrophy. AB - Computed tomographic features of 7 cases of the late infantile form of MLD confirmed by sural nerve biopsy are presented. Diffuse symmetrical white matter, low attenuation of the cerebral parenchyma was the common feature. Hypodensity of the temporal lobes and the cerebellar hemispheres are 2 features which have not been reported earlier. Three patients had brainstem atrophy without evidence of cerebral atrophy. Awareness of the various CT features of MLD may help in more definitive radiological diagnosis of the disease and to differentiate it from other dysmyelinating diseases of the central nervous system. PMID- 2929271 TI - Symptomatic hemidystonia of delayed onset. Magnetic resonance demonstration of pathology in the putamen and the caudate nucleus. AB - We present a case of symptomatic hemidystonia of delayed onset. The primary disease was a perinatal, presumed cerebrovascular infarction brought about by febrile illness with convulsions 12 weeks after partus. After many years without neurological symptoms, the hemidystonia started in adolescence, and became stationary after 4 years of mild progression. Magnetic resonance imaging revealed atrophy of the right striatum including the caudate nucleus and putamen. The symptoms responded moderately to treatment with benzhexol. PMID- 2929272 TI - Red blood cell fatty acids in multiple sclerosis. AB - The fatty acid (FA) composition of each phospholipid constituent of the red blood cells (RBC) was analyzed, by thin-layer and gas chromatography techniques, in 61 multiple sclerosis (MS) patients and 61 normal subjects, in whom the plasma lipid FA composition had previously been studied. The MS patients showed a significant decrease in the proportions of linoleic and arachidonic acids in most phospholipids, with a compensatory increase of saturated FA. Correlations between FA percentages in plasma and cell lipids demonstrated abnormalities in the MS patients, suggestive of a disturbance in the exchange between these compartments. The alterations reported in plasma and RBC in the MS patients are consistent with a relative deficiency of essential FA. PMID- 2929273 TI - Relationship between primitive reflexes, extra-pyramidal signs, reflective apraxia and severity of cognitive impairment in dementia of the Alzheimer type. AB - Controversy exists in the literature about the significance of primitive reflexes (PR) and extrapyramidal signs (EP) as diffuse cortical dysfunction signs and their relationship to age and cognitive impairment. A sample of 91 patients with a dementia of the Alzheimer type were examined with a standardized technique to assess the relationship between the finding of PR, EP and severity of cognitive impairment measured by Mini-Mental Status Examination. The value of a short cognitive test, the reflective apraxia (i.e. imitation of meaningless gestures), were also assessed. A significantly lower MMS score was correlated with the number of present PR and with presence of snout, sucking and grasping reflexes. No correlation was found between presence or absence of PR and age, depression, or drug therapy. EP score was correlated with the number of present PR and MMS, but not with age. Reflective apraxia score was significantly correlated with the degree of cognitive impairment and was found with lower cognitive impairment than PR. PMID- 2929274 TI - Somatosensory evoked potentials in the evaluation of patients with stocking/glove paresthesias. AB - We studied 10 patients referred for suspicion of peripheral neuropathy. They all complained of paresthesias with a stocking distribution. As EMG, motor and sensory nerve conduction studies failed to confirm the clinical diagnosis, we studied somatosensory evoked potentials (SEP) following median and tibial nerve stimulation. The SEP findings were compared with controls and 10 spastic paraplegias. The evoked potential study revealed prolonged latencies of cortical potentials after tibial nerve stimulation in all the patients with paresthesias and were considered evidence of myelopathy. PMID- 2929276 TI - Environmental bias in the practice of orthopedics. PMID- 2929275 TI - The problem of transient global amnesia definition. PMID- 2929277 TI - Bone-mass distribution in the femur. A cadaver study on the relations of structure and strength. AB - We measured the bone density and volume in the femoral head, cervicotrochanteric, midshaft, and condylar regions by quantitative computed tomography of the femora of 26 elderly cadavers. We also measured the shearing force at fracture of the femora in axial bending; 25 fractures occurred vertically in the neck and only one in the shaft. The bone mass-related measurements, calculated as the product of bone density times volume, increased steadily from the femoral neck down to the condyles. The bone densities of males and females did not differ, whereas the bone volumes were higher in males. Several correlations were found between the ultimate shearing force of the cervical trabecular/cortical bone and cortical and cancellous bone densities in different locations of the femur. The ultimate shearing force was correlated with the bone mass in all the locations. PMID- 2929278 TI - Mineral content and strength of lumbar vertebrae. A cadaver study. AB - Fifty-two cadaveric spine-motion segments were tested in compression alone and in combined compression-flexion to determine whether the compressive strength of lumbar vertebrae varied with the direction of the applied load, that is, whether similar relationships existed between the compressive strength and the amount of bone mineral depending on the direction of the loading. The bone mineral content (BMC) ranged between 1.6 and 5.8 g/cm and the ultimate strength between 810 and 10,090 N. The BMC of the motion segments was correlated with their strength irrespective of degree of flexion during testing (0-15 degrees). For compression flexion within physiologic limits, the first part of the motion segment to fail was, with few exceptions, the end plate and the adjacent spongy bone. PMID- 2929279 TI - Fracture patterns in two types of autosomal-dominant osteopetrosis. AB - Thirty-five individuals with autosomal-dominant osteopetrosis were interviewed and radiographs were reviewed. Twenty had the radiographic Type I osteopetrosis, characterized by diffuse, symmetric osteosclerosis and pronounced sclerosis of the skull with a thickened cranial vault. Fifteen had Type II, where the most striking findings were diffuse symmetric osteosclerosis, "Rugger Jersey Spine," and endobones (bone within a bone) in the pelvis, while the cranial vault was almost unaffected. Of the 12 probands who had had a fracture, 2/20 were Type I and 10/15 were Type II. Fracture complications were also more frequent in Type II. PMID- 2929280 TI - Antibiotic treatment insufficient for established septic arthritis. Staphylococcus aureus experiments in rabbits. AB - We treated septic arthritis of the knee in 38 rabbits with cloxacillin i.m. once and twice daily combined with probenecid for 7 or 21 days, respectively, or with only cloxacillin i.m. thrice daily for 7 days. The animals were killed weekly in groups up to 5 weeks after inoculation. Aspirated cultures obtained after 4 days of treatment were always negative. Histologic specimens revealed progressive joint destruction, but at a slower rate after frequent treatment independent of the period. We concluded that antibiotic therapy alone could not prevent destruction of articular cartilage once bacterial arthritis was established. PMID- 2929282 TI - A case of giant-cell tumor of the clavicle. PMID- 2929281 TI - Indomethacin and bone remodeling. Effect on cortical bone after osteotomy in rabbits. AB - Remodeling in cortical bone close to a plated tibial midshaft osteotomy was histomorphometrically evaluated in 32 rabbits. The animals were divided into two groups, one being treated with indomethacin (10 mg/kg per day) and the other receiving placebo. In the placebo-treated group, the remodeling activity was higher in the osteotomized leg compared with the intact leg. Two and 6 weeks after osteotomy, the number of resorptive and formative foci was reduced in the indomethacin-treated group compared with the placebo group. Porosity did not differ between the groups after 2 weeks; but after 6 weeks, it was reduced in the indomethacin-treated animals. Throughout the study, the bone formation rate did not differ between the two groups. This study demonstrates that indomethacin inhibits the remodeling of traumatized bone. PMID- 2929283 TI - School screening for scoliosis. PMID- 2929284 TI - Early loosening of the uncemented total hip. PMID- 2929285 TI - Patellar motion analyzed by magnetic resonance imaging. AB - We have analyzed the normal patellar motion during the first 30 degrees of knee flexion by magnetic resonance imaging (MRI). Ten males and 10 females without knee symptoms were examined. The patellar articulation was imaged both sagittaly and axially with the knee flexed 0, 10, 20, and 30 degrees. The axial images were produced through the middle of the patellar articular cartilage. When the knee was in extension compared to 30 degrees flexion, the sulcus angle was greater, the lateral patellofemoral angle was smaller, there was more lateral patellar displacement, the patella tilted more laterally, and the congruence angle was directed more laterally. Differences between males and females were found. PMID- 2929286 TI - Patellectomy for chondromalacia. AB - Fifteen patients with 17 patellectomies for chondromalacia were evaluated after an average of 5.5 years. The average age was 38 years. No knees were rated as excellent, whereas 5 were rated as good, 9 as fair, and 3 as poor. However, 10 patients, including both bilateral patellectomies, were satisfied with the results. PMID- 2929288 TI - Patellar angle in Osgood-Schlatter disease. AB - A new patellar angle is described in lateral radiographs of the knee joint. One line is drawn along the articular surface of the patella and another from the end of the inferior articular cartilage to the patellar apex. The angle formed by these two lines averaged 33 degrees in 68 knees joints afflicted with Osgood Schlatter disease and 47 degrees in 71 age-matched controls and 198 adult controls. The small angle in Osgood-Schlatter disease is proposed to be an important factor in the pathogenesis of the traction apophysitis. PMID- 2929287 TI - Advancement of the tibial tuberosity for patellar pain. A 5-year follow-up. AB - During the period 1978-1984, 38 patients aged 23-55 years were treated for patellofemoral pain by the Maquet procedure. The mean postoperative observation time was 5(3-9) years. Thirty-three of the 38 patients were available for follow up including functional and activity scoring, clinical examination, and Cybex II dynamometer muscle-strength measurement. Ten patients improved, 17 were unchanged, and 6 were worse. Characteristic for the improved group was Grades III and IV chondromalacia - mainly involving the lateral facet - whereas the group with no improvement or deterioration exhibited a low-grade chondromalacia, chiefly affecting the medial patellar facet. PMID- 2929289 TI - Arthroscopic resection of meniscal flaps of the knee. AB - We describe the results of arthroscopic partial resection of isolated flap tears of the menisci in 37 patients who were randomly selected for review from the hospital records. The results were compared with those in a control group of 39 patients that underwent diagnostic arthroscopy during the same period. The follow up of the patients after 1 to 2 years was based on a questionnaire. The patients with resected flap tears did better than the controls, who usually suffered from minor degenerative changes of the knee joint. However, the flap-tear patients with otherwise usually normal arthroscopic findings often continued to have discomfort and failed to gain a normal Lysholm score. PMID- 2929290 TI - Poor results of bovine xenograft for knee cruciate ligament repair. AB - In 28 patients the anterior cruciate ligament of the knee was substituted with a bovine bioprosthesis (Xenograft). Five patients underwent reoperations due to synovitis and graft rupture during the first postoperative year; and 2 patients, due to graft rupture after 3 years. After 3 years, 11/21 patients with a remaining graft had a rupture. Totally, 18/28 implanted grafts were considered to be ruptured. Our results indicate that the Xenograft in its present form should not be used. PMID- 2929291 TI - Silicone arthroplasty for hallux rigidus. Implant wear and osteolysis. AB - Between 1980 and 1985, silicone hemiprostheses were implanted because of hallux rigidus in 58 feet of 43 patients who were followed up after an average of 5 years. The majority were satisfied and had good function without pain. However, the toes had shortened because of implant wear, and there was considerable associated osteolysis. PMID- 2929292 TI - Chronic lateral instability of the ankle. Roentgen stereophotogrammetry of talar position. AB - Using roentgen stereophotogrammetric analysis (RSA), we investigated the talar mobility in 54 ankles during the anterior drawer and adduction tests. Talar tilt was increased in ankles with unilateral symptoms of chronic lateral instability. No other difference in talar tilt and anterior drawer sign was noted comparing ankles with and without symptoms. We conclude that mechanical tests cannot always verify the diagnosis "chronic lateral instability of the ankle". PMID- 2929294 TI - Operations for impingement of the shoulder. Early results in 52 patients. AB - This is a prospective study of 52 consecutive patients with impingement syndrome of the shoulder who underwent an anterior acromioplasty according to Neer with rotator cuff repair and/or a resection of the lateral end of the clavicle added where it was indicated. There was a full-thickness tear in 14 cases. The follow up was 11 months. The overall results were excellent-good in 40 patients and fair poor in 12 patients. If two out of three of the following criteria were present, the patient had an increased risk for a fair or poor result: age greater than 50 years, sick leave greater than 6 months, or an associated cervical problem. PMID- 2929293 TI - Fluorescein angiography for predicting healing of foot ulcers. AB - Fluorescein angiography (FA) was performed on 83 patients (68 diabetics) with foot ulcer or gangrene. Densitometric measurements were made on the FA images, and different FA parameters were defined. These parameters, as well as systolic ankle and toe blood pressures, were evaluated for predicting the future course, i.e., whether healing would occur or whether major amputation below or above the knee had to be performed. The toe slope (i.e., the rate of increase of fluorescence on the big toe during the first 10 seconds after its appearance on the toe) predicted healing correctly in 0.83 and major amputation in 0.88. The ankle and toe pressures had only slightly lower predictive value. The combination of ankle pressure and toe slope predicted healing correctly in 0.91 and major amputation in 0.88. When ankle pressure cannot be measured, FA is the method of choice. Further, FA provides information on regional blood flow unobtainable by any other method. PMID- 2929296 TI - Closed rereduction of axial compression in Colles' fracture is hardly possible. AB - Totally, 146 Colles' fractures that were displaced after the primary reduction were treated by closed rereduction and plaster immobilization. A permanently acceptable position was achieved in 11 of 27 cases, where dorsal angulation was the only malalignment. In fractures with both axial compression and dorsal angulation, both displacements improved to a permanently acceptable position in only 7 of 105 cases, and only the dorsal angle improved to an acceptable position in 26 cases. The axial compression was most difficult to correct. The chances of achieving a permanently acceptable position by rereduction are rather small in Colles' fracture with axial compression alone or combined with deviation of the dorsal angle. High age and the presence of dorsal comminution are further factors likely to worsen the prognosis. PMID- 2929295 TI - External fixation of Colles' fracture. AB - Radiographic and functional results of external fixation of 32 Colles' fractures were compared with the results of plaster fixation of 189 Colles' fractures. Despite the fact that the fractures treated with the external device were more unstable and comminuted, the final results were equal in both groups, and the radiographic outcome of external fixation was superior. Pin loosening decreased with predrilling rather than self-tapping. We recommend external fixation for unstable fractures of the distal forearm. PMID- 2929297 TI - Fixation not needed for undisplaced Colles' fracture. AB - A series of 68 undisplaced or minimally displaced Colles' fractures was randomized into two groups undergoing treatment with either a plaster cast or an elastic bandage. Pain, function, grip strength, and range of motion were evaluated 1 year later. There was a difference in the functional outcome in favor of the patients treated with an elastic bandage, who did not have more fracture redislocations than those treated with a plaster cast. PMID- 2929298 TI - Brace treatment of Colles' fracture. AB - Twenty patients with Colles' fractures were treated with a functional brace that allows wrist motion. The result was compared with a similar group of patients treated with a plaster cast. Dorsal displacement of the fracture was less and wrist function was better in the brace group. Swelling of the hand during the early stages was observed in the brace group; and because this may necessitate brace adjustment, increased medical supervision is necessary for this period. PMID- 2929299 TI - Normal pinch strength. AB - The normal pinch strength was determined with the Mannerfelt-Ulrich intrinsic meter in 90 men and women aged 21-65 years. The pinch strength decreased with increasing age. The ratio dominant/nondominant hand was 1.12, 0.13 (mean, SD) for both men and women. The ratio would be useful in evaluating pinch strength under pathologic conditions. PMID- 2929300 TI - Early loss of fixation of femoral neck fractures. Comparison of three devices in 244 cases. AB - In successive series of displaced subcapital femoral neck fractures in the elderly, we operated on 75 cases with three Gouffon screws, 94 with three Mecron screws, and 75 with two von Bahr screws. Redisplacement within 3 months occurred in 20 Gouffon cases, 11 Mecron cases, and 12 von Bahr cases. Poor reduction contributed to the failures in all the groups. Although the reduction results in the three groups were similar, the Mecron group had better fixation and better social recovery than the Gouffon group. We concluded that, in addition to good reduction of the fracture, solid screws also contributed to the stability of the bone-implant construct. PMID- 2929301 TI - Rehabilitation at home after hip fracture. AB - Two series of patients with a hip fracture, sustained at home, were assessed regarding utilization of rehabilitation resources before and after adoption of an active policy favoring rehabilitation at home. Out of 86 consecutive patients in 1985 (Series I), 22 were discharged directly to their home versus 44 out of 84 in 1986 (Series II). Four months after the fracture, 57 and 63 of the surviving patients in Series I and II, respectively, were at home. Twenty of the 77 surviving patients in Series I were permanently institutionalized compared with 14 of 77 in Series II. We conclude that an active attitude towards home rehabilitation after a hip fracture benefits patients and the community alike. PMID- 2929302 TI - Nine-year follow-up of the cementless Ring hip. AB - Because of the revived interest in cementless hip prostheses, 238 Ring prostheses from the period 1968 to 1979 were reviewed; 127 hips with a median follow-up of 9 years were available for examination. Two thirds of the hips were rather painless, and 90 percent of the patients graded their result as excellent or good. Six hips had had a deep infection requiring removal of the prostheses in two hips, and 37 prostheses were removed because of loosening. By actuarial analysis the overall probability of survival and the average annual probability of removal were found to be 81 and 1.7 percent, respectively, after 12 years. The long-term survival of the Ring prosthesis seems to be comparable to the survival of some commonly used cemented prostheses. PMID- 2929303 TI - Failure of a bovine xenograft for reconstruction of the anterior cruciate ligament. AB - Fourteen patients with gross anterior instability had the anterior cruciate ligament reconstructed with a bovine xenograft. Major problems with swelling, pain, and synovitis were encountered in 13 patients, of whom 3 developed a synovial fistula. Histologic evidence for allergic reactions was found in 3 patients. Revisional surgery had to be performed in 10 patients because of substantial problems or rupture of the graft. At 3 years, there was only one possibly functioning graft. The 3 nonrevised patients were unstable at clinical examination. This type of reconstruction cannot be recommended for clinical use. PMID- 2929304 TI - Poor fixation of the Mittelmeier hip prosthesis. A clinical, radiographic, and scintimetric evaluation. AB - We have evaluated 30 Mittelmeier hips on an average 3.3 years after the operation. Seven hips had been revised because of severe pain and mechanical loosening and one because of fracture of the threaded ceramic cup. Only five of the remaining 22 hips were asymptomatic. There was radiographic migration of the acetabular and femoral components in more than one third of the hips and increased scintimetric values around the femoral component in all but two hips. Unfavorable design of the Mittelmeier prosthesis may be an important etiologic factor contributing to poor component fixation and inferior clinical results. PMID- 2929305 TI - Lack of correlation between femoral neck anteversion and acetabular orientation. Radiography and computed tomography in cadavers and in vivo. AB - Radiography and computed tomography measurements were made of femoral neck anteversion, femoral head cartilage distribution, and the orientation of the acetabulum. The measurements were made in elderly cadaver femurs and in patients. They failed to establish any correlation between the femoral neck anteversion and the orientation of the articulating surface of the femoral head, nor between the femoral neck anteversion and the angles of the acetabulum. PMID- 2929306 TI - Hip motion related to age and sex. AB - In a selected population 4 years old to adult age, 1,522 hips in 761 healthy subjects of both sexes were studied. Arcs of passive motion of the hip were measured by the technique recommended by the American Academy of Orthopaedic Surgeons. The lower and upper limits of normal range of hip motion in all the planes were established for both sexes in the different age groups. We found that the amplitude of most hip motions decreased with age. Females had higher ranges of total hip motion, total rotation, internal rotation, and abduction compared with males. PMID- 2929307 TI - Colonization of middle ear pathogens in the nasopharyngeal opening of the Eustachian tube during secretory otitis media. AB - Colonization of middle ear pathogens (S. pneumoniae, H. influenzae and B. catarrhalis) in the nasopharyngeal opening of the Eustachian tube (NO) was charted in 94 patients (170 ears) suffering from secretory otitis media (SOM). Subsequent determination of microorganisms in the middle ear effusion was performed. 76% of the patients had colonization of pathogens in the NO, while pathogens colonized the middle ear cavity (MEC) in 30% of the cases. Predominant pathogen was S. pneumoniae, followed by B. catarrhalis and H. influenzae. When colonizing the MEC, there was a 100% correlation to NO regarding B. catarrhalis, 81% correlation for S. pneumoniae and 57% for H. influenzae. S. aureus and/or coagulase-negative staphylococci were only occasionally found in the NO. Accumulation of a sticky glue effusion material in the middle ear cavity may serve as a barrier against ascending pathogens from the nasopharynx. PMID- 2929308 TI - Recurrent acute otitis media. A prospective study of children during the first three years of life. AB - To evaluate possible risk factors for developing recurrent acute otitis media (rAOM), 113 children were followed prospectively from birth to the age of 3 years. One of the aims was to determine whether such risk factors could be identified before the onset of the recurrences, so that optimal care and prophylactic measures could be made available at an early stage in such cases, on the basis of continuous follow-up by an ENT specialist. During the follow-up, 13 children developed rAOM, defined as six or more episodes of acute otitis media (AOM) during a 12-month period, 57 children had occasional episodes of AOM, and 43 children had no AOM at all. Of the children with onset of AOM before 6 months of age, 80% developed frequent episodes of AOM. The frequency of other respiratory tract infections and of family histories of otitis-proneness was higher among rAOM children than among the other children. The development of rAOM was unrelated to such factors as sex, familial history of allergy, duration of breast-feeding, or domestic environment. Nor could attendance at day-care centres be concluded as constituting a risk factor for the development of rAOM. An onset of AOM before 6 months of age was highly predictive of subsequent recurrent bouts of AOM, which emphasizes the importance of correct diagnosis in infants. PMID- 2929309 TI - Histological changes in the nasal mucosa in persons occupationally exposed to formaldehyde alone and in combination with wood dust. AB - In the nasal mucosa of rodents, both formaldehyde and wood dust have proved to be carcinogenic. Wood dust is also a well-known nasal carcinogen in man. The effects of long-term exposure of humans to formaldehyde, however, are more obscure. In this investigation two groups of workers with well-defined exposure to formaldehyde and to formaldehyde and wood dust, respectively, were compared with a control group regarding histological changes in nasal specimens from the middle turbinate. Significant changes were found in the formaldehyde group but not in the group exposed to both formaldehyde and wood dust. No correlation was found between histological changes and duration of exposure, doses of exposure or smoking habits. PMID- 2929310 TI - Histological reaction to polyimide films in the cochlea. AB - The biocompatibility of commercially available polyimides was examined in relation to the sensory and neural structures of the cochlea. Thin films of four different polyimides were prepared as substrates for photolithographically produced scala tympani electrode arrays and implanted in 32 cat cochleae. Following at least three months implantation time, the animals were sacrificed and the cochlea were evaluated histologically for toxicity, differences in the severity of ototoxic effects among the four polyimide groups, and relationships among the different kinds of histopathology secondary to implantation. Findings included the following. Inflammatory reaction to the implants, when present, was generally mild and confined to the immediate vicinity of the implant. Additionally, ototoxic effects were essentially the same across the four groups. Finally, a clear interdependence among the different kinds of cochlear damage secondary to implantation was demonstrated. PMID- 2929311 TI - CR1-expression and C3b-mediated phagocytosis of granulocytes in purulent maxillary secretion and peripheral blood from patients with sinusitis. AB - Granulocytes in sinus pus and in peripheral blood in 28 patients with maxillary sinus empyema were compared to blood granulocytes obtained from healthy blood donors. A flow cytofluorometric assay technique was used to establish the C3b mediated phagocytosis and the CR1-receptor expression. The results indicate that a subpopulation of viable granulocytes in situ was activated with an increased ability to ingest particles. From 11 of 28 patients, an increased CR1-expression was also demonstrated in the blood samples, reflecting a priming of the circulating granulocytes before extravasation. PMID- 2929313 TI - Premalignant lesions of the larynx. A follow-up study. AB - The object of this investigation was to evaluate in the long-term the risk of malignancy occurring in the larynx of patients with dysplasia in the laryngeal epithelium. Over an 8-year period, 1974-82, 170 patients underwent microlaryngoscopic examination of the larynx including biopsy, showing hyperplasia and/or keratosis with or without dysplasia in the laryngeal epithelium. Of these, 147 patients were examined, on an average, 5 years and 4 months later. All histological specimens were reviewed by the same pathologist. Of the patients initially showing mild dysplasia, 7.8% developed aggravation while 55.6% of the patients displaying moderate dysplasia had developed severe dysplasia or carcinoma. 93.2% were smokers. It is concluded that all patients with atypia in the laryngeal epithelium should be observed at regular intervals, but special attention should be given to patients showing moderate dysplasia or worse. PMID- 2929312 TI - The cricothyroid muscle after cricothyroidotomy. A porcine experimental study. AB - Cricothyroidotomy in elective use or emergency situations has been discussed by several authors during recent years. The main complication reported has been subglottic stenosis. We have used this method for several years and among our patients there has been no case of stenosis. The major complication in our material has been voice dysfunction. Some of the patients had a change in voice quality consistent with dysfunction in the cricothyroid muscles (diminished voice range and a lowered pitch). The aim of this study was to investigate whether cricothyroidotomy and insertion of a tracheostomy tube caused physiological or morphological changes in the cricothyroid muscle, by direct injury or secondary to a peripheral nerve lesion. In the six animals that were cricothyroidotomized during 7-9 days and examined after 9-15 weeks, we found neither changes in the EMG nor in the muscle morphology indicating injury to the muscle or its peripheral nerve supply. PMID- 2929314 TI - Non-organic dysphonia. II. A comparison of subglottal pressures in normal and pathological voices. AB - In previous investigations, typical phonetogram differences have been revealed between healthy and pathological voices: the average maximum and minimum sound pressure levels that a patient suffering from non-organic dysphonia can produce at different fundamental frequencies deviate significantly from the corresponding values for a healthy voice. The subglottal pressure, being the primary tool for regulating the sound pressure level of voice, was estimated from the oral pressure during the voiceless stop/p/in 10 female and 10 male subjects with normal voices and in 10 female and 10 male non-organic dysphonic patients. In loud phonation, the female patients had significantly lower values than the female healthy subjects, while no corresponding significant difference was seen between the male subjects. In soft phonation, the male patients had significantly higher values than the normal healthy subjects, while the females showed no significant difference. PMID- 2929315 TI - Prolonged electrode implantation in experimental studies. Critical evaluation of a technique. AB - Stainless steel electrodes were chronically implanted through the right facial canal of 30 guinea pigs, close to the potential generator (VIII nerve). Compound action potential (CAP) thresholds, N1 latencies and input-output curves were recorded on day of implantation and 2, 4 and 8-12 weeks later. In the same sitting, auditory evoked brain stem response (ABR) thresholds, latencies and inter-peak-latencies were measured on both sides as a control. N1 thresholds and latencies at low and high intensities were stable. N1 amplitudes, however, showed some variation. Rate of infection was low and reimplantation was successful. Preserving the facial nerve as a land mark was found advantageous, particularly on reimplantation, and did not affect the CAP recording. The technique, originally described by Hildesheimer et al., proved to be reproducible. A few technical difficulties are pointed out and the implication of some interesting findings are discussed. PMID- 2929316 TI - Comparative anatomy of melanin pigment in the stria vascularis. Evidence for a distinction between melanocytes and intermediate cells in the cat. AB - Although Corti in 1851 first described the presence of cochlear pigmentation in the stria vascularis (SV) of "very old" cats, modern studies have failed to find pigment consistently in the feline stria. While the variable presence of pigment in the feline SV would appear to contrast with this structure's uniform pigmentation in other mammalian species, variability in both the distribution and abundance of inner ear pigment has rarely been studied in any species. In the present study, the SV was examined light microscopically in sectioned material or whole-mounts from pigmented and albino animals of 5 species, including the cat, guinea pig, rabbit, ferret and mouse. In these species, the SV of each pigmented animal contained varying amounts of melanin pigment and none was found in the albino inner ear. Pigmented guinea pigs contained the most uniformly dense and least variable distribution of strial melanin, followed by the rabbit, mouse, ferret and cat. Several species also displayed more strial pigment apically and less basally. In cats, pigmented cells were principally located adjacent to the strial capillaries. Ultrastructural studies of the stria in pigmented cats revealed that these perivascular cells frequently contained an abundance of pigmented organelles and other structural features which allowed them to be distinguished from intermediate cells. PMID- 2929317 TI - Surgical trauma to the cochlea results in reversible damage to spiral ganglion type I neurons. AB - Type I neurons are reversibly damaged when the cochlear bony wall is opened. The reversibility is indicated by the absence of neuronal loss, as demonstrated by quantification of the spiral ganglion neuronal population. Reversible damages included ultrastructural signs of excessive ion and water influx into the type I neuron cytoplasm, whose functional implications must be investigated in the future. PMID- 2929318 TI - Alterations in oxygenation of cochlear endolymph during loud sound exposure. AB - The oxygen tension (pO2) of endolymph of the guinea pig cochlea was measured during exposure to loud sound (12 kHz or high-pass noise; 110 dB SPL up to 1 h duration). A small, but significant, steady decline in mean pO2 was observed after both pure tone and high-pass noise exposure. The extent of the change in pO2 varied from 0-50% in individual animals, compared with unexposed control animals. All exposed animals had an extensive loss of compound action potential (CAP) thresholds at frequencies of 8-30 kHz. However, there was no relationship between the extent of the change in pO2 of endolymph and CAP threshold loss. PMID- 2929319 TI - Healing of experimentally produced round window membrane rupture. AB - The healing mechanism of experimentally produced ruptures of the round window was histologically studied in guinea pigs. Surgically created rupture of the round window resulted in spontaneous closure within 2 weeks. Light microscopical examination indicated that the rupture closed with proliferation of connective tissue which usually appeared to protrude into the middle ear cavity, each case showing a unique shape. In one case, the wound was covered with granulation tissue at the site of closure on the middle ear surface. Although the rupture was closed by connective tissue, the elastic fibres of the middle layer remained disrupted at the early stage of healing. PMID- 2929320 TI - Failure of gaze stabilization under high-frequency head oscillation. AB - Gaze functions under high-frequency head oscillations with large amplitudes were investigated in 12 normal subjects. Oscillation amplitude decreased as the frequency increased (31 degrees at 2 Hz to 11 degrees at 5 Hz on average). Maximum head velocity and acceleration were 170-200 degrees/s and 2,500-5,000 degrees/s2, respectively. At frequencies higher than 2 Hz, the mean ratio of eye amplitude to head amplitude reached high large values (1.2 at 2 Hz to 1.8 at 5 Hz, on average), whereas it dropped to extremely low values (0.5-0.6 at 3-5 Hz) in the 2 referred patients with bilateral labyrinthine loss. High ratio values, different from the previous reports, may result from a failure of compensation due to abnormally high-frequency and large head oscillations. The present study indicated that the frequency range of VOR influenced by gaze should correspond to that of daily-experienced oscillations, and that once head oscillations exceed the limit, compensation quickly deteriorates. PMID- 2929321 TI - Elevation of inner ear antibody levels following direct antigen challenge of the endolymphatic sac. AB - The effect of direct antigen challenge of the endolymphatic sac (e.sac) on inner ear antibody levels was investigated in guinea pigs. Two weeks following e.sac antigen inoculation, perilymph antibody levels to keyhole limpet hemocyanin (KLH) were found to be significantly elevated in the challenged ear of those animals compared to the unchallenged, opposite ear. Moreover, when the endolymphatic duct (e.duct) in a group of animals were obstructed prior to antigen challenge of their e.sac then the rise in perilymph antibody was prevented. The local accumulation of plasma cells and lymphocytes in the perisaccular space and e.sac lumen was seen following these antigen injections. These experiments suggest that inner ear antibody emanates from the e.sac and reaches the perilymphatic compartment along the route of the e.duct. Furthermore, these findings emphasize the central role of the e.sac in inner ear immunity. PMID- 2929323 TI - Effect of crossed stapedius reflex on vibration of mallear handle in man. AB - The ear drum was made to vibrate using frequency-modulated sound pulses of 40 ms duration, and the vibration velocity of the tip of the mallear handle (umbo) was measured with laser vibrometry before and during stapedius muscle contractions (elicited by sound of 100 dB HL in the contralateral ear). The stapedius reflex caused: an attenuation of the mallear vibrations below 1 kHz, a slight enhancement of the vibrations between 300 Hz and 1,500 Hz. These effects of the stapedius reflex appear to be caused by an increased stiffness in the structures affecting the mallear vibrations. PMID- 2929322 TI - Development of cochlear-wall implants for electrical stimulation of the auditory nerve. AB - The aim of these experiments was to investigate the use of titanium implants for anchorage of stimulating electrodes or other clinical or experimental devices in the bony wall of the cochlea. Twenty-six cylindrical titanium fixtures, 0.6 mm in diameter, were inserted into holes drilled in the otic capsule in 8 ears in 5 nonhuman primates and then examined for stability after periods of 2 months to 2 years. Following sacrifice, the bone-metal interfaces were examined microscopically. Fourteen of the implants were firmly fixed in the bone, 6 were loosely fixed and 6 came out. Poor fixation was associated with infection in the middle ear. In uninfected ears, 90% of the implants were stable. The implants were not osseointegrated in the classic sense, but in stable implants, direct bone contact covering 5 to 60% of the titanium oxide surface of the implant shaft was observed. PMID- 2929324 TI - Tympanic membrane structure during a Staphylococcus aureus-induced middle ear infection. A study in the rat middle ear. AB - In response to a Staphylococcus aureus-induced middle ear infection the tympanic membrane showed infiltration of polymorphonuclear granulocytes, lymphocytes, and macrophages and increased areas covered by ciliary and secretory epithelium. These reactions, which were comparable to the cellular and mucociliary responses seen in the middle ear mucosa during infection, were restricted to the pars flaccida and to predominantly the annular and manubrial regions of the pars tensa. This showed that the greater part of the tympanic membrane, where the lamina propria is composed of collagenous bundles and only very thin layers of loose connective tissue, is hardly affected by or barely responds to the inflammatory stimulus. PMID- 2929325 TI - Vascular corrosion casts of the nasal mucosa. An experimental study in the rabbit. AB - Ten-rabbits of either sex, weighing between 1.8 and 2.7 kg were used for studies on the angioarchitecture of the nasal mucosa of the septum and the anterior concha. Via the common carotid artery, Batson's corrosion compound No. 17 was introduced into the vascular system of the nose after rinsing with Ringer's solution. After digesting the connective tissue between the vessels, vascular corrosion casts were obtained. The replica of the endonasal angioarchitecture offers a unique opportunity to examine the various vascular layers of the nasal mucosa as well as the junction and relationships between different vessels in the different levels of the tunica propria. Our results can be regarded as a useful extension of earlier investigations in this field. PMID- 2929326 TI - Confirmation of encapsulated nerve structures in the human vocal cord. AB - The overall morphology of the encapsulated nerve structure in the human vocal cord was studied. The nerve consists of a straight portion containing a striated muscle fiber and several side branches. The side branches consist of non myelinated fibers and dense collagen bundles. Their ultrastructure resembles that of the Golgi tendon organ, suggestive of a pressure receptor. Since the side branches extend between muscle fibers of the vocal muscle, their purpose may be to detect the stiffness of the vocal cord. One end of the intracapsular muscle fiber terminates in the capsule and the other, tapered end terminates in dense collagen bundles within the capsular space. Contraction of muscle fiber alters the stiffness of the intracapsular space and may control the sensory threshold of the nerve ending. PMID- 2929327 TI - Comparative histochemistry of human and sheep laryngeal muscles. AB - Four laryngeal muscles of human male, human female and sheep female cadavers were evaluated by histological, histochemical and quantitative techniques. The muscle fibre sizes showed significant differences between human male, female and sheep. Fibre diameters of male human laryngeal muscles were 2 to 4 microns larger than in female human and 11 to 13 microns larger than in sheep muscles. In the group of human laryngeal muscles, the posterior cricoarytenoid muscle contained the highest percentage (65%) of type I fibres. In sheep, the homologous muscle consists only of 45% type I fibres. On the other hand, in sheep the cricothyroid muscle showed significantly more type I fibres (58%) than the human counterpart (43%). In both species the vocal muscles had a rather low content of type I fibres (26 to 37%). PMID- 2929328 TI - Treatment of vocal cord granuloma. AB - Combined surgical and conservative therapy (voice therapy, treatment of infections, allergy, oesophageal reflux, and psychogenic stress) has been used in the treatment of non-specific vocal cord granuloma. Such tumors have a great tendency to recur. The 41 patients with vocal cord granuloma in our study (4 women, 37 men, mean age 56 years) were treated at our hospital during 1980-1986. Nine patients were healed with conservative treatment, 32 were treated by laryngomicrosurgery under general anesthesia and jet-ventilation. The latter group was divided into three treatment groups; 8 of these patients were treated with cryotherapy, 9 with postoperative steroids (Prednisolone 40 mg/day in decreasing doses) and antibiotics, and 15 only with microsurgery. At some phase in their treatment 41% of the patients were able to participate in voice therapy. The most recurrences were found in the group treated with cryotherapy, 2.7 rec./pat.; 1.8 rec./pat. were found in the group that underwent surgery, and 1.7 rec./pat. among the patients treated with steroid-antibiotics. In all three groups, some patients experienced recurrences. In the cryotherapy group, however, recurrent granulomas were large and required reoperation, while those in patients treated with steroid-antibiotics were small and could be cured using conservative therapy. If granuloma does not disturb the voice, cause respiratory obstruction or demand histopathological diagnosis, surgery is contraindicated. Cryotherapy does not help traditional surgery, while steroid-antibiotics administered postoperatively seem to help the healing process. PMID- 2929329 TI - The healing of cricothyroidostomy in pigs. A morphological study. AB - The advantages and disadvantages with cricothyroidotomy have been discussed by several authors during the last 12 years. The frequency of complications differs considerably probably depending on indications for surgery and methods of follow up. In our own human material (253 patients cricothyroidotomized and 79 of 102 alive after 6 months followed up) there has been no case of laryngeal or tracheal stenosis. The aim of this study was to analyse the effect of the inflammatory granulation tissue on the surrounding tissues in 8 cricothyroidotomized pigs, and to analyse the regeneration of the mucosa and the healing with special regard to development of stenosis. Despite pronounced stomal infection and formation of granulation tissue we found no case of stenosis, no injuries of the cartilage and a complete regeneration of the ciliated epithelium. PMID- 2929330 TI - Morphology of tracheal scar after resection with CO2-laser and high-frequency cutting loop. A study in normal pigs. AB - In 6 pigs a bronchoscopical resection of the tracheal mucosa was performed using CO2-laser on one side, and an electric high-frequency cutting loop (ECL) on the other. The pigs were sacrificed 3 months later. On macroscopic examination the tracheal mucosa appeared almost normal on the laser-resected side, while severe deformation was seen after ECL treatment. Microscopically the respiratory epithelium had regenerated irrespective of the instrument used. After laser resection the subepithelial tissue had a normal width and consisted of collagen fibrils with few vessels and sparse fragmented elastic tissue. The cartilage showed necrosis and pericellular fibrosis. The scar tissue after ECL was a broad cellular and richly vascularized connective tissue. The content of elastic fibres was markedly greater than after laser resection. The cartilage showed small irregular necroses lined by pyknotic nuclei. In neither case had the gland regenerated. Both CO2-laser and ECL caused severe (but not identical) damage to the tissue, clearly visible after 3 months. However, the deformation caused by ECL was not seen at the laser-resected sites, which makes the laser technique seem preferable--where economy permits. PMID- 2929331 TI - Interactions between the middle ear and the inner ear. 3rd International Academic Otologic Workshop. August 23-25, 1987, Umea, Sweden. PMID- 2929332 TI - Effects of round window membrane rupture on cochlear blood flow and inner ear pressures. AB - Effects of round window membrane rupture on cochlear blood flow and inner ear pressures were investigated using non-radioactive microspheres and a servo micropipet system in guinea pigs. When perilymphatic pressure was raised through a glass capillary tube inserted into the perilymphatic space, both endolymph pressure and perilymph pressure rose. When these inner ear pressures were raised to relatively high levels, cochlear blood vessels could be compressed and endocochlear potential decreased to a negative value due to the interruption of cochlear blood flow. However, in the case when the round window membrane was ruptured by further increase in perilymph pressure, the inner ear pressures decreased and restoration of cochlear blood flow and endocochlear potential was observed. When the round window membrane was ruptured with a fine needle under ordinary inner ear pressures, cochlear blood flow did not change significantly. PMID- 2929333 TI - Role of the round window membrane in middle ear immune responses. PMID- 2929334 TI - A rat model for bacterial otitis media. AB - Rat middle ear was exposed to challenge with viable pneumococci, type 3 and 6A, and the course of changes in the middle ear was observed by otomicroscopy and analysis of bacterial samples from blood, nasopharynx and middle ear effusions. Microscopical examination of changes in the middle ear mucosa during and after the acute infection was also made. Depending on the type and concentration of pneumococci, three different results were observed: otitis media with purulent effusion, otitis media with serous effusion, or no reaction at all. The mortality rate was low and most animals recovered within 10 days without postinfectional changes visible by otomicroscopy. The microscopical examination of the middle ear mucosa revealed distinct changes. Inoculation of rat middle ear with pneumococci causes a self-limiting infection that closely resembles acute otitis media in the human. Thus the rat would seem to be a suitable animal model for the study of bacterial otitis media. PMID- 2929335 TI - The effect of gestation on eustachian tube function in rats. AB - Patulous Eustachian tube (tuba aperta) is a distressing condition for the patient with such symptoms as autophony and a sensation of fullness in the ear. One-third of women with the diagnosis are pregnant or taking oestrogens. To study whether opening of the Eustachian tube is facilitated during pregnancy, the tube opening function of 14 pregnant rats was compared with that of 14 non-pregnant controls. The middle ear air pressure at which the tube opened (the pressure opening level, Pol) was lower in pregnant rats than in controls; and the difference between Pol and the pressure during open tube (at continued air injection) was less in the pregnant rats. In two additional rats it was then demonstrated that instillation of a surface tension lowering substance in the middle ear caused similar pressure changes as occur during pregnancy. It is concluded that opening of the Eustachian tube in rats is facilitated in pregnancy, and it is suggested that this is due to a reduction in surface tension of the Eustachian tube secretion. PMID- 2929336 TI - Structure of the round window membrane. AB - In the present study the literature on the round window membrane (RWM) structure was reviewed and the rat used as an animal model to elucidate structural alterations of the RWM occurring during serous (SOM) and purulent (POM) otitis media. In SOM the RWM was about the same thickness as that of the control, whereas in POM it increased about 5-fold. The structural changes in POM were mainly confined to the epithelium facing the middle ear cavity. The normal flat epithelium was transformed into a pseudostratified epithelium with both ciliated and goblet cells. Light microscopy revealed only minor changes in the RWM structure during SOM. However, ultrastructurally, the connective tissue layer exhibited dense accumulations of collagen and elastic fibres which were not observed in either normal or the POM ears. The study showed that different inflammatory conditions of the middle ear cause different structural alterations of the RWM. To what extent these changes also influence differently the permeability of the RWM remains to be elucidated. Obviously ultrastructural studies are needed to be able to characterize the structural changes which appear in the RWM in a diseased ear. PMID- 2929337 TI - Round window membrane permeability. An in vitro model. AB - The round window membrane of the mongolian gerbil was dissected out, together with its bony niche. The preparation was mounted between two glass chambers representing the middle ear cavity and the perilymphatic space respectively. Passage through the round window membrane did not occur within 3 h when testing high-density lipoprotein with a molecular weight 115-350 kD. Horse-radish peroxidase, with a molecular weight of 48 kD, passed the round window membrane at a mean rate of 6 micrograms/h when the concentration of the protein was 10 g/l in the middle ear chamber. The present in vitro model is considered to be free from leakage artifacts between the chambers. Passage rates for different substances through the round window membrane can be calculated under controlled conditions using this type of in vitro model. PMID- 2929338 TI - Sensory hair fusion and glycocalyx changes after gentamicin exposure in the guinea pig. AB - This study demonstrates the mechanism of sensory hair fusion and its relationship to glycocalyx on the inner ear sensory cells of gentamicin-treated guinea pigs, using the ruthenium red staining technique. 0.5 ml containing 5 mg gentamicin sulfate solution was injected in a single dose into the middle ear. After 7 days, various stages of sensory hair degeneration could be observed. The glycocalyx was clearly visualized by ruthenium red. The degeneration starts with a decrease in or even complete loss of glycocalyx in the sensory hairs, with subsequent local adhesion of the plasma membrane in neighbouring hairs. These findings suggest that the glycocalyx of the sensory cell may play an important role in separating the cilia, yet keeping them in a bundle. PMID- 2929339 TI - Middle ear ototoxic treatment for inner ear disease. AB - Twenty-nine patients seriously disabled by Meniere's disease due to frequent attacks were treated with Gentamicin administered in the middle ear once daily until first sign of an inner ear disturbance, usually a spontaneous nystagmus and a sensation of unsteadiness. All patients except one were relieved from their vertiginous attacks and returned to normal activities. Tinnitus was usually diminished or absent, as was the feeling of pressure in the ear. The hearing was slightly improved in 5 patients, worse in 9 patients and two treated ears became deaf. The indication for an intratympanal treatment with Gentamicin should be a disabling form of Meniere's disease not responding to medical treatment. The risk for the cochlea increases after 6 days of treatment. The advantage versus intracranial surgery is the absence of the surgical risks for complications. The mode of action exerted by the ototoxic drug is a destruction of the vestibular sensory epithelium and the endolymph producing cells. PMID- 2929340 TI - Development of a human milk protein standard. AB - Accurate quantitation of the protein content of human milk (HM) is clinically important for both determining protein and energy intakes of HM-fed infants. Protein can be determined by Kjeldahl analysis or colorimetric assays. Colorimetric assays are rapid and convenient, but usually overestimate the protein content when compared to Kjeldahl protein (KP). In this study a protein standard based on human milk protein (HMPS) was isolated by size exclusion column chromatography. Purity and composition of the standard was determined by gel electrophoresis, Kjeldahl and amino acid analyses. The protein content of 20 mature milk samples was determined by the Lowry, BCA and BioRad colorimetric assays, using bovine serum albumin, human serum albumin/IgG, and HMPS as standards. These results were compared with KP results using Student's t-test. All colorimetric assays overestimated milk protein content; however, the Lowry assay gave the lowest protein levels, with our protein standard yielding values closest to the KP value. PMID- 2929341 TI - Neonatal outcome of extremely small low birthweight liveborn infants below 901 g in a Swedish population. AB - In a regional population of 32,120 liveborn newborn infants 65 (0.2%) had a birthweight less than or equal to 900 g (extremely small low birthweight = ESLBW) with mean gestational age 26.4 (range 22-31) completed weeks of gestation. The total 0-1 year survival rate was 48%. For the 42 infants treated in the Level III regional neonatal intensive care unit (NICU) the 0-1 year survival rate was 55% versus 34% for 23 infants not transferred to the Level III unit. In the ESLBW infants treated in the regional NICU the major complications were respiratory disorders requiring artificial ventilation (73%), bronchopulmonary dysplasia (26%), intracranial haemorrhages (40%), symptomatic persistent ductus arteriosus (36%) and sepsis (14%), persistent retinopathy of prematurity (8%). Duration of NICU treatment was 51 days (range 10-95) for survivors. Mode of delivery and rate of perinatal complications did not differ between survivors and non-survivors. Previous legal abortion occurred in 24%, fertility problems in 29% and 21% of the mothers were immigrants. Otherwise no significant abnormalities were found in maternal or socioeconomic conditions. Factors deciding neonatal outcome in the tiniest babies seem to be a combination of prenatal circumstances and neonatal minute fine care procedures. PMID- 2929342 TI - Oxygenation, heart rate and temperature in very low birthweight infants during skin-to-skin contact with their mothers. AB - Fourteen very low birthweight infants were studied positioned either prone horizontal or skin-to-skin at 60 degree tilt between the mother's breasts. Heart rate, skin temperature and oxygenation by transcutaneous PO2 and pulse oximetry were measured. Nine of the infants had normal lungs when studied. These infants showed no change in tcPO2 or oxygen saturation but heart rate increased significantly by a mean of 6.5 beats per min during skin-to-skin contact. Five infants with chronic lung disease, including two on nasal catheter oxygen, showed a significant 1.0 kPa rise in tcPO2 during skin-to-skin contact. Back skin temperature was well maintained during skin-to-skin contact with the room temperature at 26 to 29 degrees C. None of the infants had a significant apnoea or bradycardia during the study. Stable very low birthweight infants can enjoy such close contact with their mothers and the tilted position may improve pulmonary function in some cases. PMID- 2929343 TI - The evolution of a simplified method for interpretation of EEG in the preterm neonate. AB - We describe the evolution of a simplified method for the interpretation of serial EEG in preterm neonates which was tested in a first sample and revised and improved in a second sample of preterm neonates. There were 185 EEGs in the first sample and 206 EEGs in the second sample. The interpretation of the EEGs was related to mental, motor and neurological outcome in late infancy. Serial EEG is an excellent indicator of brain function in the preterm neonate. PMID- 2929344 TI - Prediction of the development of neonatal jaundice by increased umbilical cord blood bilirubin. AB - Umbilical cord serum bilirubin concentration as a predictor of subsequent jaundice was studied in 291 newborns. It was possible to define subgroups of infants with significantly higher or lower risks of developing jaundice. If cord bilirubin was below 20 mumol/l, 2.9% became jaundiced as opposed to 85% if cord bilirubin was above 40 mumol/l. Furthermore, 57% of jaundiced infants with cord bilirubin above 40 mumol/l required phototherapy, but only 9% if cord bilirubin was 40 mumol/l or lower (p less than 0.003). Knowledge of infants at risk of developing jaundice allows simple bilirubin reducing methods to be implemented before jaundice is present and could influence a decision regarding early discharge from hospital. Since the ability of plasma to bind bilirubin in cord blood from jaundiced and non-jaundiced infants showed no significant differences, the increased cord bilirubin among infants who later became jaundiced is presumably caused by increased fetal bilirubin production or decreased removal of bilirubin from the fetal circulation. PMID- 2929345 TI - Secular trends of sudden infant death syndrome and other causes of post perinatal mortality in Norwegian birth cohorts 1967-1984. AB - Lack of positive diagnostic criteria and increasing professional concern, probably causing increasing ascertainment, have rendered reported increases in SIDS-rates controversial. However, these problems related to cause specific mortality do not apply to the total mortality. Due to the exceptional age-at death distribution of SIDS cases, the SIDS fraction of all deaths increases during the first year of life to reach a maximum, in the present study of 56%, from the 105th through the 125th day of life. During these days, the total mortality rate in Norway increased from 0.24 per 1,000 in 1971-72 to 0.46 in 1983 84. Thus, the observed trend, with an increase in the SIDS rate from 1.02 per 1,000 in 1971-72 to 2.34 in 1983-84, is considered true. Observed in a country where perinatal and neonatal mortality have decreased for a long period of time and still remain very low in a global perspective, the increasing SIDS rate is a matter of great concern. PMID- 2929346 TI - Influence of sex and gestational age on cord blood IgE. AB - Cord blood IgE (CB-IgE) is widely used as a screening parameter for atopy. Therefore it is necessary to define the normal values accurately. In this study influence of sex and gestational age on CB-IgE is evaluated. 5,305 cord blood samples were analysed. Boys had a higher CB-IgE than girls (p less than 0.001). Using a cut-off value for normal of 2.4 micrograms/l, boys had significantly more abnormal values than girls (p = 0.0475). Using a lower cut-off value (2.16, 1.92, 1.68 micrograms/l) the difference became more significant (p = 0.0029, p = 0.0036 and p = 0.0019 respectively). Gestational age (in the range from 34-42 weeks of gestation) had no influence on the absolute CB-IgE concentration nor on the number of abnormal values. From this study we may conclude that, when CB-IgE is used in prediction and prevention programs for atopic disease, the sex of the newborn should be taken into consideration when evaluating the results, in particular when the cut-off limit is lowered. No correction needs to be made for gestational age if the baby is born after the 34th week of gestation. PMID- 2929347 TI - The natural history of IgE sensitisation and atopic disease in early childhood. AB - We have prospectively followed 57 children of atopic parents up to 5 years of age, documenting clinical atopic disease and allergen skin test reactions. The cumulative prevalences of the clinical features of atopic disease over the 5 years were: atopic dermatitis (58%), wheeze (49%), recurrent wheeze (33%), rhinitis (68%) and immediate food reactions (18%). Atopic dermatitis and immediate food reactions predominated in infancy (birth to 20 months) while wheezing was more prominent in later childhood (20 months to 5 years). Rhinitis was common in both infancy and childhood. IgE sensitisation to ingested allergens was prominent in early infancy and was usually transient. Inhaled allergen sensitisation occurred later in infancy and was generally permanent with wheal sizes tending to increase with age. There was a significant association between IgE sensitisation to ingested but not inhaled allergens and all atopic manifestations in infancy, with the exception of rhinitis. In contrast IgE sensitisation to inhaled allergens was associated with rhinitis and wheeze in later childhood. We found two clinical groups. One group, with only ingested allergen sensitisation had a high incidence of atopic dermatitis but low incidence of respiratory symptoms at 5 years of age. The other group, who developed evidence of IgE sensitisation to inhaled allergens, had a high incidence of rhinitis and wheeze but low incidence of atopic dermatitis at 5 years of age. PMID- 2929348 TI - Allergic diseases in Swedish school children. AB - The occurrence of allergic diseases in children was studied on the basis of a questionnaire sent to the parents of 20,000 school children, 7, 10 and 14 years of age, in 3 parts of Sweden with different climatic conditions. The prevalence of asthma was 2.4%, allergic rhinoconjunctivitis 7.4%, eczema 7.8% and total allergic diseases 16.9%. The prevalence of all diseases was significantly higher in the northern part of the country than in the southern parts. This geographic variation was not related to heredity, infant feeding pattern or known exposure variables other than the cold and dry climate. Parental history of allergic diseases increased the incidence in the offspring 2-9 times, with a pattern of symptom specificity and a cumulative effect of double parental history. Breast feeding postponed the onset of allergic disease only in children with double parental history. PMID- 2929349 TI - Effect of an acidified milk on diarrhoea and the carrier state in infants of low socio-economic stratum. AB - The effect on diarrhoeal disease of an acidified, modified powdered cow's milk infant formula (Pelargon) was evaluated in 82 infants (Group I) for six months; 104 infants who received the same formula but non acidified, served as controls (Group II). Nutritional status remained satisfactory in both groups throughout the observation period. Some children rejected the taste of the acidified milk. The incidence of diarrhoea was lower in Group I (p less than 0.001). The proportion of days in which the children suffered from acute diarrhoea, and the duration of the episodes were also lower in the children given the acidified milk (p less than 0.001). The rate of detection of enteropathogens and the species identified were comparable in both groups. Carrier rates for bacterial enteropathogens fell over time in Group I while they rose in Group II (p less than 0.001). Carrier rates for enteric parasites were comparable to those expected in our setting for this age group. These results suggest that acidified milk exerts a protective effect against diarrhoeal disease. PMID- 2929350 TI - Hyperferritinemia in malignant histiocytosis, virus-associated hemophagocytic syndrome and familial erythrophagocytic lymphohistiocytosis. A survey of pediatric cases. AB - Data on 28 patients with malignant histiocytosis (MH), fourteen patients with virus-associated hemophagocytic syndrome (VAHS) and two patients with familial erythrophagocytic lymphohistiocytosis (FEL) were collected from 21 hospitals in Japan to study the serum ferritin levels and clinical features. At diagnosis, the serum ferritin values were a median of 3,000 ng/ml (range, 59-270,000 ng/ml) in MH and 10,500 ng/ml (range, 44-68,600 ng/ml) in VAHS/FEL. Clinical signs and symptoms were not substantially different between MH and VAHS/FEL. Thus, serum ferritin markedly increased in the majority of MH/VAHS/FEL patients and should be a useful marker of disease activity in either neoplastic or reactive histiocytic proliferative disorders. PMID- 2929351 TI - Plasma amino acids in relation to metabolic control in insulin-dependent diabetic children. AB - The influence of metabolic control (estimated by blood glucose, 3-hydroxybutyrate and glycosylated hemoglobin levels) on plasma amino acids was determined in a group of 56 insulin-dependent diabetic children. A multiple correlation analysis revealed significant positive partial correlations between most amino acids and blood glucose. Alanine, methionine, tyrosine, phenylalanine and arginine showed negative partial correlations to the 3-hydroxybutyrate level. The results are consistent with the postulate that ketone body inhibition of muscle proteolysis is one of the factors regulating substrate flows during insulin deficiency. PMID- 2929352 TI - Epilepsy and mental retardation following febrile seizures in childhood. AB - In an unselected group of children who were seen following an initial febrile convulsion, the frequency of subsequent afebrile seizures was 3.5% and of mental retardation 1%. The most common afebrile seizure type was generalized major (86%). About 3/4 of the children who developed afebrile seizures did so by three years and all by five years following the initial febrile seizure. The children with afebrile seizures differed from those without afebrile seizures in the frequency of neonatal abnormality, family history of mental retardation, focal initial febrile convulsions, and delay in psychomotor milestones before the initial febrile seizure. Only about 1/3 of the children who developed afebrile seizures ever had a recurrent febrile convulsion and none had complex recurrent febrile seizures. Half the children with mental retardation had histories of delay in psychomotor milestones prior to the initial febrile seizure, and no child with mental retardation had any seizure longer than five minutes. The administration of daily phenobarbital did not reduce the frequency of epilepsy, in spite of a significant reduction in the incidence of recurrent febrile seizures. There remains no evidence that the prevention of recurrent febrile convulsions significantly decreases the frequency of afebrile seizures or mental retardation. PMID- 2929353 TI - The effect of the number of fractions of cranial irradiation on growth in children with acute lymphoblastic leukaemia. AB - Growth was documented over a period of 7 years in all long-term survivors treated for acute lymphoblastic leukaemia (ALL) with the DAL-70- (n = 15) and BFM-70 protocol (n = 27). Normal growth was documented in patients of the DAL-70 protocol during and after therapy. In contrast, in children treated with the BFM 70-protocol the mean height standard deviation score (SDS) decreased significantly from 1.21 SDS prior to therapy to 0.80 SDS at the end of therapy (p less than 0.001) and remained unchanged thereafter. Prophylactic cranial irradiation was given in total doses of 15 to 30 Gy. Ten children of the DAL-70- and 20 children of the BFM-70-protocol received 24 Gy of cranial irradiation. No significant change in height-SDS was observed in any patients of the DAL-70- and in 8 patients of the BFM-70- group, who received 24 Gy of cranial irradiation in 16-26 fractions. Adult height in 7 girls and 6 boys was normal and 3.15 cm and 5.06 cm above target height. In the remaining 12 patients of the BFM-70-protocol the total dose of 24 Gy of cranial irradiation was applied in 11-14 fractions. Their height-SDS had fallen significantly from 1.24 SDS before to 0.66 SDS (p less than 0.001) at the end of therapy. Adult height in 4 girls and 6 boys was also normal, but the height increase was comparatively smaller, -2.20 cm below target height in the girls and 1.91 cm above in the boys.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2929354 TI - Vitamin D status of Hong Kong Chinese infants. AB - Vitamin D deficiency is a common nutritional problem of weaning infants in many parts of the world. Hong Kong infants, who are fed with traditional rice-based weaning foods and live in crowded high rise flats, might be expected to suffer from this nutritional problem. Yet a study of 150 bottle fed infants revealed that the vitamin D intake from fortified milk and cereals was more than half of the recommended amount throughout the first 18 months and that the serum 25-OH vitamin D concentration of the infants at 18 months was normal. The effect of sunlight was also evident. PMID- 2929355 TI - Reference values of anthropometric measurements in Dutch children. The Oosterwolde Study. AB - In the period 1979-1980 the following anthropometric measurements were recorded in 2351 healthy Dutch children from 0-17 years of age: height, weight, sitting height, arm span, lengths of upper-arm, lower-arm and hand, tibial length, foot length, biacromial diameter, biiliacal diameter, and head circumference. Corresponding percentile values were constructed on the basis of normality assumptions, the mean and standard deviation at age t being determined by a cubic spline approximation. The results are compared with other studies and given in the form of growth charts. PMID- 2929356 TI - Autistic behaviour in Moebius syndrome. AB - Seventeen children and young adults with Moebius syndrome were examined with a view to finding symptoms of autism. Some 40% of the group showed all or many of the symptoms typical of autistic disorder. The high frequency of autistic symptoms in Moebius syndrome might be a marked overrepresentation and could be suggestive of a common underlying neurobiological deficit at the brainstem level. PMID- 2929357 TI - Pulmonary resections in cystic fibrosis. PMID- 2929358 TI - Molybdenum. Normal plasma values at delivery in mothers and newborns. PMID- 2929359 TI - Effect of maternal anaemia and iron depletion on foetal iron stores, birthweight and gestation. PMID- 2929360 TI - Function of peripheral blood granulocytes in infants with protracted enteropathy. PMID- 2929361 TI - The ceruloplasmin and transferrin system in cerebrospinal fluid of acute leukemia patients. PMID- 2929362 TI - Non-tropical pyomyositis in children--with report of severe neurological complications. AB - Pyomyositis appears to occur rarely in temperate climate areas, compared with the incidence of the disease in the tropics. Three young adults with pyomyositis have previously been described in Israel, two of them were newly arrived Ethiopian immigrants. We report three Israeli children with pyomyositis, who presented initially with nonspecific abdominal pain; in one child the course was complicated by spinal cord compression due to extension of the infected mass into the spinal canal. All three patients attained full recovery after antibiotic therapy and surgical drainage. Computed tomography was most valuable in establishing the diagnosis and defining the extent of the process. PMID- 2929363 TI - Unitary activity in the bed nucleus of the stria terminalis after homo- and contralateral stria terminalis stimulation. AB - Acute experiments were performed on anaesthetized rats using standard techniques of electrical stimulation and single-unit recording in order to study the responses of the bed nucleus of the stria terminalis (BNST) neurons to homo- and contralateral stria terminalis (ST) inputs. Satisfactory records were obtained from 174 BNST neurons. The majority of these fired spontaneously at variable rates, with single random-occurring spikes. The stria terminalis inputs are able to influence the discharges of many BNST neurons. Homolaterally the response patterns consisted of: (a) an excitatory-inhibitory sequence with variable latency in 61% of the cells; (b) a pure inhibitory period in 23% of the cells; (c) an inhibitory period followed by excitation in 2%; (d) no changes in 13% of the cells. The most frequent response to contralateral ST stimulation was excitation followed by inhibition (46%) and pure inhibition (28%). A high proportion of the cells (27%) did not show any change. These results correlate well with neuro-anatomical studies of ST distribution on the BNST nucleus. Our finding of the high proportion of BNST cells affected in their discharge frequency by ST stimulation together with the variability of the observed responses is an indication of the close amygdala-BNST relationship and also of the diverse functions in which both structures are involved. PMID- 2929364 TI - Spermidine/spermine-N1-acetyltransferase activity in isoprenaline-stimulated rat salivary glands. AB - In parotid, sublingual and submaxillary glands stimulated by continuous intravenous infusion of isoprenaline at various doses for 3 h, the concentrations of the polyamines putrescine, spermidine, spermine and N1-acetylspermidine as well as the activities of ornithine decarboxylase and spermidine/spermine-N1 acetyltransferase were determined. Ornithine decarboxylase is the enzyme that catalyses the formation of putrescine from ornithine. The most striking effect was observed in parotid glands. Here, the beta-adrenergic agonist increased the activity of spermidine/spermine-N1-acetyltransferase markedly, but only slightly (if at all) that of ornithine decarboxylase. It also increased the concentrations of N1-acetylspermidine and putrescine markedly. The result obtained in this gland indicates interconversion of higher polyamines to putrescine. PMID- 2929365 TI - Receptors involved in the nervous system regulation of polyamine metabolism in rat salivary glands. AB - Polyamines are important for protein synthesis and tissue growth. In rat salivary glands, the activity of ornithine decarboxylase (ODC), the enzyme catalysing the formation of putrescine, and the content of putrescine, spermidine, spermine and N1-acetylspermidine were assayed after parasympathetic or sympathetic nerve stimulation in the presence of various autonomic receptor blockers. Increases in ODC activity occurred on activation of non-adrenergic and non-cholinergic receptors in response to parasympathetic nerve stimulation and on activation of alpha(alpha 1)- as well as of beta(beta 1)-adrenoceptors in response to sympathetic nerve stimulation. Moreover, in parotid glands, a beta(beta 1) adrenoceptor-mediated inverse pathway for putrescine formation seemed to exist: from spermidine via N1-acetylspermidine. PMID- 2929366 TI - Carbachol stimulation of inositol phosphate accumulation in rat submandibular gland fragments is not modified by VIP. AB - Formation of inositol phosphates in response to carbachol, phenylephrine and vasoactive intestinal polypeptide (VIP) was studied after labelling with [3H]myo inositol in rat submandibular gland fragments. Carbachol enhanced the accumulation of inositol phosphates in a concentration-dependent manner. This effect was independent of calcium in the incubation medium and totally antagonized by atropine (IC50 = approx. I nM). Phenylephrine also induced an increase in inositol phosphate accumulation, which was totally antagonized by prazosin but not by atropine. Vasoactive intestinal polypeptide, isoproterenol and forskolin, compounds known to enhance the levels of cAMP in rat salivary gland, or addition of dibutyryl-cAMP (DB-cAMP) failed to alter basal or carbachol evoked accumulation of inositol phosphates. It is concluded that the formation of inositol phosphates during muscarinic receptor stimulation with carbachol in rat submandibular gland fragments is not affected by adrenoceptor occupation or by cAMP. In particular, addition of VIP, which coexists with acetylcholine, did not alter the muscarinic inositol phosphate response. PMID- 2929367 TI - Flow resistance in the feline choledocho-duodenal sphincter as studied by constant-pressure and constant-perfusion techniques. AB - During interdigestive periods, there is a resistance to flow in the biliary tract exerted by the sphincter of Oddi, resulting in a pressure gradient between the common bile duct and the duodenum. In this experimental study, this flow resistance was studied with both a constant-flow and a constant-perfusion technique in fasted, anaesthetized cats. The flow resistance exerted by the sphincter is higher when it is perfused by a constant flow compared to when the common bile duct pressure is kept constant and the flow varies in response to its muscular activity. It was demonstrated with each method that the flow resistance in the choledocho-duodenal junction is reduced in response to distension of the biliary tree and gallbladder and also by distension of the duodenum. Cholecystokinin was shown to reduce the flow resistance in the choledocho duodenal junction as estimated with either method. PMID- 2929368 TI - Influences of the sympatho-adrenal system on gastric motility and acid secretion and on gastroduodenal bicarbonate secretion in the cat. AB - Experiments were performed on acutely vagotomized cats during chloralose anaesthesia. Gastric H+ and HCO3- secretions were calculated from the pH and PCO2 in a luminal perfusate. Gastric motility was reflected by changes in hydrostatic pressure within the luminal perfusion system ('intragastric pressure'). Duodenal HCO3- secretion was monitored by pH titration in situ. Animals with an intact sympatho-adrenal system (group 1) were compared with others subjected to splanchnicotomy (group 2), adrenal gland ligation (group 3), and splanchnicotomy plus adrenal gland ligation (group 4). Basal gastric H+ secretion, as well as vagally induced H+ secretory responses, did not differ significantly between groups. Basal gastric HCO3- secretion was lower in all groups with a manipulated sympatho-adrenal system compared to the intact controls. Vagally induced increases in gastric HCO3- secretion were enhanced in the splanchnicotomized groups (groups 2 and 4). Basal as well as vagally induced increases in intragastric pressure and duodenal HCO3- secretion were enhanced in animals subjected to splanchnicotomy, with or without simultaneous adrenal gland ligation (groups 2 and 4). Adrenal gland ligation per se had no such effects. The results suggest that the adrenal glands exert a stimulatory action on basal gastric HCO3- secretion. Basal intragastric pressure and basal duodenal HCO3- secretion are inhibited by post-ganglionic sympathetic neurons, not involving the adrenal glands. Also, vagal excitatory effects on gastric motility, as well as on gastric and duodenal HCO3- secretions, are inhibited by such a direct neural mechanism. PMID- 2929369 TI - Extravascular arteriovenous oxygen shunting in the cat stomach. AB - Venous appearance of oxygen and red cells labelled with methaemoglobin was compared in the gastric vascular bed. At 'resting' gastric blood flow the red cells appeared earlier than oxygen after simultaneous close i.a. injection, as would be expected from the intravascular laminar flow profile. However, when lowering arterial inflow pressure to the stomach by partially occluding the coeliac trunk, oxygen often appeared earlier than the red blood cells. When arterial pressure was lower than 50 mmHg this was always the case. This observation is taken to indicate that during these experimental conditions an extravascular shunting of oxygen occurs. It is suggested that this may occur in the submucosal vascular network and/or in the mucosa. The functional implications of such a mechanism are tentatively discussed. PMID- 2929370 TI - Effect of acute intravenous volume loading on haemodynamics and aortic baroreceptor activity in dogs. AB - This study evaluates the effect of acute intravenous volume loading on haemodynamics and aortic baroreceptor activity in order to determine the mechanistic factors responsible for divergent heart rate responses to volume loading. Eleven beagles were anaesthetized and instrumented for the recording of aortic pressure, diameter, flow and aortic baroreceptor activity. Isotonic saline, equal to 20% of the estimated blood volume, was infused intravenously within 60-90 s. The animals were divided into tachycardiac and bradycardic groups according to their heart rate response to volume loading. In the group developing the tachycardic response, aortic baroreceptor activity increased. Total peripheral resistance was reduced by 31% and variables representing aortic stretch, mean aortic pressure, diameter and tension remained unchanged. In contrast, in the group developing the bradycardiac response, aortic baroreceptor activity increased markedly. Also in this group peripheral resistance decreased, but only by 15%, which was significantly less than in the tachycardiac group. Factors determining aortic stretch, mean aortic pressure, diameter and tension also increased significantly. Earlier studies show that regardless of the resulting heart rate response, atrial receptor activity increases during volume loading. Thus, we conclude that during cardiac acceleration, marked peripheral vasodilation eliminates the stimulation of baroreceptors and therefore the tachycardic response caused by atrial receptors develops. In the case of cardiac slowing, vasodilation also takes place, but is not sufficient to prevent activation of baroreceptors. In consequence, increased baroreceptor activity overrides the tachycardic drive coming from the atrial receptors and a typical baroreceptor reflex becomes manifested. PMID- 2929371 TI - Electrophysiological and mechanical characteristics of isolated hearts from spontaneously hypertensive (SHR) and normotensive (WKY) rats on very high- and low-sodium diets. AB - Electrophysiological, mechanical, dimensional and coronary flow characteristics were studied on papillary strips and on isolated hearts, from spontaneously hypertensive (SHR) and normotensive (WKY) rats respectively, which from 5 to 15 weeks of age had been on either 'low' (LNa, 0.5 mmol 100 g-1 food), control (CNa, 5) 'high' (HNa, 50) or 'very high' (vHNa, 120) sodium diets. With respect to cardiac electrophysiological characteristics, contractility, and maximal stroke volume capacity only minor, if any, differences were observed between the various Na diet groups, both in WKY and SHR. This is in accordance with our earlier findings concerning vascular smooth muscle, where a largely unchanged sensitivity and responsiveness to, for example, noradrenaline was noted. Further, only to the extent that the various Na diets had also caused changes in average blood pressure levels, adaptations of cardiac and coronary resistance vessel design were observed, in general agreement with our earlier findings in other preparations and experimental designs. The largely unaffected functional characteristics of cardiac as well as vascular effector cells, despite 240-fold long-term variations in sodium intake, are in sharp contrast to the marked changes that have been shown to affect the adrenergic nerves, as here chronic low Na intakes cause reductions of transmitter release/impulse, and vice versa at high Na intakes. This latter type of change seems to be by far the most important functional deviation affecting cardiovascular control during long-term alterations of sodium intake, as it can markedly affect both cardiac and vascular influences on haemodynamics, even though the respective effector functions seem to be surprisingly little influenced directly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2929372 TI - Renal response to low and high phosphate intake in weanling, adolescent and adult rats. AB - The renal response to low and high phosphate intake was studied in weanling, young and adult rats. Weanling rats were started on experimental diets containing 0.37%, 0.7%, or 1.7% phosphate at 24 days and adult rats at 60 days of age. After 21 days, clearance studies were done in anaesthetized animals. Urine was collected during basal conditions and following a phosphate infusion. Urinary excretion of calcium, phosphate and creatinine, and plasma levels of phosphate and creatinine were determined. Plasma phosphate was slightly higher in the younger rats in all dietary groups but was not influenced by phosphate intake in either age group. Urinary phosphate excretion and fractional phosphate excretion increased significantly in both age groups with increasing phosphate intake. After high phosphate intake, both net and fractional phosphate excretions were significantly higher in younger rats (0.97 +/- 0.08 and 0.24 +/- 0.06 mumol min-1 100 g-1, P less than 0.01, and 47.5 +/- 3.84 and 18.15 +/- 5.59%, P less than 0.01, respectively). The urinary excretion of calcium related to creatinine was higher in younger rats in all dietary groups with the highest value found after low phosphate intake. During an acute phosphate infusion, fractional phosphate excretion increased significantly in both age groups after normal phosphate intake but remained unchanged after low or high phosphate intake. Plasma phosphate increased significantly only in younger rats with high phosphate intake (2.9 +/- 0.18, 3.88 +/- 0.43, P less than 0.05). It is suggested that hypercalciuria reflects early stages of phosphate depletion and that in young rats stabilized on a high phosphate intake, phosphate retention may occur during an acute phosphate load. PMID- 2929373 TI - Effects of reduced oxygen tension on endothelium-dependent relaxation induced by acetylcholine differ in rabbit femoral artery and jugular vein. AB - In intact rabbit femoral artery rings pre-contracted with phenylephrine, acetylcholine (ACh; 10(-9)-10(-6) M) produces endothelium-dependent relaxation, abolished after mechanical rubbing to remove the endothelium. The response to ACh was absent at low oxygen tension (less than or equal to 4 kPa) or in the presence of sodium cyanide (1 mM). Intact rabbit jugular veins relaxed to ACh in lower concentration than did the femoral artery, 10(-10)-10(-8) M; at sufficient ACh concentration the relaxation was complete. In veins with completely removed endothelium no relaxation to ACh occurred, and at concentrations above 3 x 10(-7) M the response was a contraction. The relaxation response to ACh of intact veins persisted during contraction at lower oxygen tension or in the presence of 1 mM sodium cyanide. In rubbed veins, cyanide consistently induced a transient contraction, which was absent in intact veins. The study demonstrates pronounced endothelium-dependent relaxation to ACh in a venous preparation, with a markedly lower sensitivity of the relaxation response to hypoxia than in a muscular artery of the same species. PMID- 2929374 TI - Effect of high pressure on metabolic response to cold in rats. AB - The ability of rats to regulate body temperature in a cool helium-oxygen (heliox) atmosphere at high pressure was studied. Thermoregulatory ability in seven awake rats was assessed in a pressure chamber at 1.5, 21 and 41 ATA by monitoring body temperature and oxygen consumption during a gradual reduction of ambient temperature. Body temperature was measured by a radiotelemetry transmitter implanted into the intraperitoneal cavity. The thermal conductance of the rats increased from 0.37 to 0.75 W kg-1 degrees C-1 as air was substituted by heliox and increased further to 1.47 and 1.81 W kg-1 degrees C-1 as the pressure was increased to 21 and 41 ATA, respectively. At high pressure the rats were able to maintain body temperature until the metabolic rate reached a value of 21.9 +/- 2.0 W kg-1, which corresponds to peak metabolic rate. This occurred at an ambient temperature of approximately 21 degrees C. Below this ambient temperature the rats did not manage to maintain body temperature. The results show that the thermal effector mechanisms of rats respond adequately to a slowly decreasing ambient temperature in hyperbaric heliox environments. PMID- 2929375 TI - Autonomic nervous control of cervical secretion in the guinea-pig. AB - Neurogenic influence on cervical secretion was studied in experiments performed on isolated guinea-pig cervix with intact adjacent nerves. The secretion was estimated as carbohydrate efflux. Experiments were undertaken at ovulation time when secretion is most prominent. Hypogastric nerve stimulation significantly increased carbohydrate release. This response was unaffected by phentolamine but inhibited by TTX, scopolamine and hexamethonium, as well as previous destruction of paracervical ganglia. Pelvic nerve stimulation did not affect cervical secretion. Carbachol as well as VIP induced a secretory response of the same extent as did hypogastric nerve stimulation. Scopolamine abolished the VIP induced secretion. VIP and carbachol in combination had no additive effect. It is concluded that cervical glands of the guinea-pig uterus possess a cholinergic secretomotor innervation. The main pathway is the hypogastric nerve and neurons have a peripheral relay at paracervical ganglia. A more complex peripheral organization cannot be excluded. PMID- 2929376 TI - Comparison of tactile discrimination ability of visually deprived and normal monkeys. AB - The tactile discrimination ability of visually deprived and normal monkeys was tested to study whether loss of vision would improve the utilization of the tactual sense. Three normally sighted monkeys and three monkeys that had been deprived of vision during the first year of their life were trained in two tactile discrimination tasks by using a reward system in which the animals received a raisin or half a peanut under a correctly chosen wooden block. Discrimination was based on the gradual roughness or size of various blocks. When the monkeys had learned the tasks to the criterion, discrimination thresholds were determined. All monkeys improved their performance in both tasks with time, but no statistically significant differences between the performance of the two groups of monkeys were obtained. These results suggest that although the representation of the tactual sense in the cortical association areas has been shown to increase as a result of visual deprivation during the early sensitive period of life, increased representation does not improve the tactual discrimination ability of simple tactual stimuli. PMID- 2929377 TI - Large transcapillary hydraulic conductance in skeletal muscle and skin of man revealed by a new technique. PMID- 2929378 TI - Pacemaker-like firing of noradrenergic locus coeruleus neurons in vivo induced by the excitatory amino acid antagonist kynurenate in the rat. PMID- 2929380 TI - Characteristics of patients with major depression in combination with dysthymic or cyclothymic disorders. Childhood and precipitating events. AB - The relationship between patients with acute major depression and chronic affective disorders was investigated in 298 nonpsychotic outpatients. The patients were categorized into 4 groups: major depression only, major depression with dysthymic or cyclothymic disorders, dysthymic or cyclothymic disorder without major depression and one group of other psychiatric disorders. The patients were interviewed about childhood losses, relationship to parents and siblings and family atmosphere, their personality characteristics as children, as well as precipitating events. The reports in the various diagnostic groups were compared. Patients in the mixed group reported somewhat more traumatic childhood experiences compared with patients in the pure major depression group and pure dysthymic-cyclothymic group, and much more traumatic childhood experiences compared with patients in the group of other disorders. Precipitating events among patients in the acute major depression group consisted of more acute external stressors compared with the events of the patients in the group of chronic affective disorders. Patients with major depression in combination with pure dysthymic-cyclothymic disorder generally remembered their childhood as having been more traumatic, with a less satisfying relationship to their parents. PMID- 2929379 TI - Minor physical anomalies and recidivistic adult violent criminal behavior. AB - Minor physical anomalies (MPA) result from disruptions of gestation, and may be used as signs of central nervous system defects in development. Utilizing a Danish birth cohort, we tested the hypothesis that MPA predict adolescent and adult recidivistic violent criminal behavior. The number of MPA was measured at 11 to 13 years of age and police records of criminal behavior were ascertained at 20 to 22 years of age. Recidivistic violent offenders evidenced an elevated level of MPA compared with subjects with one violent offense or subjects with no violent offenses. PMID- 2929381 TI - An educational program on depressive disorders for general practitioners on Gotland: background and evaluation. AB - General practitioners are the psychiatrists' most important coworkers in the treatment of depressive disorders. A high degree of knowledge about this illness in this group of doctors is of decisive importance. However, the value of postgraduate educational programs for general practitioners has been questioned. The Swedish Committee for the Prevention and Treatment of Depression (PTD) offered an educational program on symptoms, etiology, diagnosis, prevention and treatment of depression to all general practitioners on the Swedish island of Gotland. Lectures on suicide, depressive illness in childhood and in old age and psychotherapy of depressive states were also given. In several control periods data were collected on suicides, referrals to the local psychiatric department, emergency admissions, the quantity of sick leave used and the quantity of inpatient care due to depression. Even the prescription of psychopharmacological drugs on the island was investigated. Overall, the results indicated that general practitioners gratefully accepted the educational program and achieved increasing competence and stringency in treating and preventing depressive states. The program was associated with decreases in the use of psychiatric inpatient care and the sick leave frequency of depressed patients. The possibility of preventing suicides was positively influenced. PMID- 2929382 TI - Lactate infusions in panic disorder patients and normal controls: autonomic measures and subjective anxiety. AB - The anxiety symptoms, heart rate and blood pressure of 61 patients who panicked during lactate infusions were compared with 25 control nonpanickers. There was no significant difference in the increase in heart rate and blood pressure over baseline between patients and controls. There appeared to be no significant correlation between the subjective anxiety ratings and the measures of heart rate and blood pressure during lactate-induced panic. The symptoms of shortness of breath, feeling frightened or afraid, feeling dizzy and fear of losing control were significantly associated with lactate-induced panic. In addition, the cognitive symptoms of fear of losing control and fear of going crazy appear to be important determinants of lactate-induced panic. PMID- 2929383 TI - Nonregressive schizophrenia--a long-term comparative follow-up investigation. AB - A 14-17 year follow-up study of a first admission sample of nonregressive schizophrenic cases revealed a phenomenological and diagnostic consistency over time. Some improved and adapted well in society but a considerable proportion developed into chronic schizophrenic syndromes. Schizophrenic deterioration was also manifested among those who adhered to a nonregressive course without ever revealing frank psychotic decompensation. Treatment consumption and disability were high. Prognosis and outcome were, in the main, similar to a parallel series of regressive schizophrenic first-admission cases of similar sex and age composition. The sex difference noted in the intermediate-term outcome study in 1973, with a more favourable outcome among the women, was no longer present. The findings added further support to the validity of the concept of nonregressive schizophrenia and to the hypothesis of a joint nosology with classical schizophrenia. PMID- 2929384 TI - Disaster severity and emotional disturbance: implications for primary mental health care in developing countries. AB - Two months following the 1987 earthquakes in Ecuador, 150 patients in the primary health care clinics of the area were screened for emotional problems; 40% of them were emotionally distressed. Risk factors included not being married, reporting poor physical or emotional health, and having ill-defined physical complaints. The findings from this research are discussed in relation to a disaster of much greater intensity, whose victims were studied by the authors, utilizing the same instrument and research design. The comparison between these 2 groups of disaster victims revealed that: 1) the prevalence of emotional distress was smaller among the Ecuador victims, but the frequency of symptoms among the distressed was similar for both groups; 2) the symptom profiles were remarkably similar; and 3) the most frequent symptoms and the strongest predictors of emotional distress were very similar. These findings support a focused training of health care workers on selected emotional problems that are regularly present among victims of different disasters. PMID- 2929385 TI - Decreased plasma benzylamine oxidase in a subgroup of schizophrenia. AB - Plasma benzylamine oxidase (BzAO) activity was analysed in a group of 40 schizophrenic patients and compared with that of healthy controls. Although plasma BzAO was significantly decreased in schizophrenics as a whole, when patients were divided into type I (favourable course) and type II (poor course) it was found that the reduced BzAO activity was only observed in type I. Several clinical features were associated with a low BzAO level. The clinical and biological significance of the identification of a biochemical alteration in a subgroup of schizophrenic patients is discussed, and we suggest that the possibility of BzAO being a marker for prognosis in schizophrenia should be further investigated. PMID- 2929387 TI - Psychalgic depressive disorder: a descriptive and comparative study. AB - In this study 35 consecutive patients diagnosed as having psychalgic depressive disorder (PDD) who lacked sadness but presented with chronic pain have been described. The patients were mainly female, middle-aged and from an urban background. Pain, usually at multiple sites, was reported to be severe by most patients. Predominant depressive symptoms were lack of interest in surroundings (97%), although this was not directly reported, early morning awakening (91%), loss of appetite (100%), and suicidal ideas (66%). None had marked sadness or weeping spells. Lack of reactivity of mood was present in only 2 cases. These psychalgic depression cases were compared with a group of 30 patients diagnosed as having psychogenic pain disorder. PDD cases were significantly more often female, married, less educated, and from an urban background. Pain was significantly more intense and at multiple sites, as compared with the psychogenic pain disorder cases. Clinical outcome was better for PDD cases. PMID- 2929386 TI - The GBS scale in multi-infarct dementia and senile dementia of Alzheimer type. AB - The GBS profile was assessed for 39 patients with multi-infarct dementia (MID) and 34 patients with senile dementia of Alzheimer type (SDAT). The MID patients fulfilled the DSM-III criteria for multi-infarct dementia and had a score of 7 points or more on the Hachinski Ischemic Scale (HIS) and a score of 4 points or less on the Gustafson/Nilsson Alzheimer Scale (GNAS). The SDAT patients fulfilled DSM-III criteria for primary degenerative dementia and had a score of 5 points or more on the GNAS and a score of 6 points or less on the HIS. The total GBS score, the GBS subscale and relative subscale scores for intellectual functioning were significantly higher in patients with SDAT as compared with patients with MID. However, these subscale scores were considerably dispersed and nearly totally overlapping between patients with MID and SDAT, which implicates that the discriminative value is minimal. The validity between the GBS versus HIS and between the GBS versus GNAS was divergent, suggesting that the GBS scale has its own unique validity. In conclusion, the study does not support the hypothesis that the GBS profile may be of diagnostic value in clinical differentiation between multi-infarct dementia (MID) and senile dementia of Alzheimer type (SDAT). PMID- 2929388 TI - Morbidity and mortality after early aneurysm surgery--a prospective study with nimodipine prevention. AB - Based on the outcome in 116 consecutive patients who were subjected to early aneurysm operation combined with additional nimodipine treatment, and who were controlled by transcranial Doppler (TCD) sonography, a morbidity and mortality analysis was performed. Of the 84 patients who preoperatively were in Hunt & Hess grades III, 79 patients (94%) were considered to show a favourable (good-fair) late recovery, while one patient (1%) had a poor outcome, and four patients (5%) died. Of the 32 poor condition patients (H & H IV-V), 17 (53%) showed a favourable recovery, while seven (22%) had a poor outcome, and eight patients (25%) died. Altogether, 20 patients (17%) had an unfavourable (poor-dead) outcome. Only two of these patients showed delayed ischaemic deterioration, one as a consequence of a secondary occlusion of perforating branches from the basilar artery and one with decompensated vasospasm after the evacuation of an epidural haematoma and a longlasting severe systemic hypotension; both these patients died. In another six of the patients with an unfavourable outcome, this was mainly related to a complicated surgery. The unfavourable outcome was related to primary brain damage produced by the subarachnoid haemorrhage (SAH) in ten patients and in two patients to internal medical complications. In addition to the two patients who died following delayed deterioration, secondary neurological dysfunction occurred in 11 patients. In 10 of these patients transient neurological dysfunction was attributed to vasospasm or to a combination of vasospasm with intraoperative or postoperative complications. One further case of delayed deterioration was attributed to secondary occlusion of the internal carotid artery after a complicated operation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2929390 TI - Surgical approach to pineal tumours. AB - During a period of 10 years (1977-1986) 40 cases of tumour of the pineal region have been treated at the Istituto Neurologico "C. Besta"-of Milan. Out of these 40 cases, 27 (67.5%) were in the paediatric (10-15 years) or juvenile (15-20 years) age at the time of operation. Since 1983 a specific diagnostic and therapeutic protocol has been adopted and thereafter direct surgical removal of the tumour was performed only when the neuroradiological investigations were highly suggestive of a benign extrinsic lesion. Sixteen cases in this series underwent direct surgical removal; in the remaining 24 cases stereotactic biopsy of the tumour was performed in the first instance. On the basis of the histological diagnosis obtained by this procedure surgical excision of the tumour (9 cases) or radiotherapy (15 cases) was then performed. 25 cases underwent surgical removal of the lesion. In all the cases the infratentorial supracerebellar approach as introduced by Krause and then modified by Stein was adopted. On analysis of the data of this series it was observed that in 25% of the cases completely benign resectable tumours were found; in 25% of the cases astrocytoma (grade I-II) which could be treated at least by partial removal were present; in 30% of the cases radiosensitive lesions were encountered. In the remaining 20% of the cases highly malignant tumours were found which should be treated only by radiotherapy and/or chemotherapy. PMID- 2929389 TI - Intracerebral subependymomas. Clinical and neuropathological analyses with special reference to the possible existence of a less benign variant. AB - The frequency of asymptomatic subependymomas was 0.4% in 1,000 serial routine necropsies and 0.7% in symptomatic subependymomas from 1,000 serial surgical specimens of intracranial neoplasms. Among patients with subependymoma (7 symptomatic and 4 asymptomatic), we found 3 cases of marked nuclear polymorphism (NP) in biopsy specimens. The subjective NP was objectively quantified by computer-assisted morphometry, by which a significant difference in nuclear size between these three cases and other cases (p less than 0.005) was revealed. This morphological characteristic correlated with the results of DNA-analysis by flow fluorescence cytometry (FFCM): subependymomas with NP demonstrated higher S and G2/M phases in a diploid pattern than other benign gliomas of our series. From the clinical data including prognosis, however, no remarkable difference was found between the NP group and other groups. The possible existence of less benign variant should be considered in the diagnosis and treatment of subependymoma. PMID- 2929391 TI - Callosotomy for the management of intractable non-focal epilepsy: a preliminary personal assessment. AB - After reviewing the data of the literature, the authors report their personal series composed of twelve cases. In evaluating the results of surgical treatment only the first ten patients are taken into account. As previously stressed in the literature, callosotomy (total in two cases and anterior in the remainder) has proved effective in abolishing or significantly reducing atonic seizures. Tonico clonic seizures have also benefitted in some cases, while in complex partial and partial seizures the effects of callosotomy have been so far unpredictable, albeit in some patients all kinds of seizures have been abolished or definitely reduced. The most impressive EEG and neuropsychological features after callosotomy are briefly summarized. Anterior callosotomy seems to be a relatively safe procedure, its results appear to be, on the whole, gratifying even though in patients with severe mental retardation and Lennox-Gastaut syndromes remain controversial. PMID- 2929392 TI - Dissociation between activation of the hypothalamo-hypophyseal antidiuretic system and the type of diuresis during acute intracranial hypertension. Experimental observation. AB - Acute cerebral compression by a supra- and infratentorial balloon produced a triphasic pattern of diuresis. The 1st phase was characterized by polyuria associated with five fold increase of plasma (p) antidiuretic hormone (ADH) concentration, decreased urine osmolality in spite of natriuresis and blood pressure elevation. The 2nd phase was characterized by oliguria, a decrease of pADH and reduced urine Na+ concentration, whereas urine osmolality transiently increased. At this stage there was respiratory arrest and fall of blood pressure. The final stage was diabetes insipidus (DI), when EEG activity had disappeared. An increase of serum osmolality mainly occurred during the last DI phase. Serum Na+ concentration fluctuated slightly during the whole period of diuresis. These results present evidence, that the diuresis pattern reflects the hypothalamo hypophyseal antidiuretic system (HHAS) reaction to acute intracranial pressure (ICP) increase with the vegetative symptoms of cerebral shock. PMID- 2929393 TI - Percutaneous insertion of CSF ventriculoatrial shunts--a new technique. Technical note. AB - In conventional techniques concerning insertion of ventriculoatrial shunt systems, the route to the caval system is accomplished by a lateral rightsided neck dissection and isolation usually of the facial or the external jugular vein, in order to introduce the atrial catheter into the internal jugular vein and consequently the superior vena cava. A new approach for catheterization of the internal jugular vein is proposed. The technique is a combination of the well proven approach for percutaneous catheterization of the vein and a technique used in the implantation of permanent pacemaker leads. We find the method suitable for cases whenever a VA-shunt is preferred. PMID- 2929395 TI - Vaccine biotechnology. PMID- 2929394 TI - Surgical treatment of multiple aneurysms. Review of experience with 372 cases. AB - We review the surgical results in 372 cases of multiple intracranial aneurysms over a 25-year period in which one of us (JS) performed 2,000 direct operations for aneurysms. All patients were classified into four groups according to the location of the aneurysm: Group 1: multiple aneurysms including anterior communicating artery aneurysm (157 cases); Group 2: multiple aneurysms of unilateral anterior circulation (72 cases); Group 3: multiple aneurysms of bilateral anterior circulation (110 cases); Group 4: multiple aneurysms including vertebro-basilar artery aneurysms (33 cases). In multiple aneurysm cases, our policy has been to treat all aneurysms, ruptured and unruptured, in a one-stage operation whenever possible. About 90% of patients in both Group 1 and 2 were treated by one-stage operations, while 60% of patients in Group 3 and 42% of patients in Group 4 were operated on in the same manner. Excellent and good results in from 73% to 81% of cases were obtained in patients in Group 1, Group 2 and Group 3. Morbidity was 14-19% and mortality was 6-8%. These results were comparable to the results with a single aneurysm of the anterior circulation. On the other hand, the surgical results in Group 4 were poor with a mortality of 27%. Poor results were attributable to the postoperative rebleeding from the untreated vertebro-basilar aneurysms, which were thought to be unruptured aneurysms preoperatively. Furthermore, it was clarified that the results of early one-stage operations (within one week from onset) in patients with multiple aneurysms were satisfactory. In this group, there was good recovery in 84% of patients, 7% were disabled and 9% died.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2929396 TI - Improvement in functional recovery of stunned canine myocardium by long-term pretreatment with oral propranolol. AB - We investigated the effect of long-term oral pretreatment with the beta adrenergic antagonist, propranolol (Inderal LA, 160 mg daily for 8 days) on the functional recovery of myocardium after 15-minute coronary artery occlusion followed by 3 hours of reperfusion in barbital-anesthetized dogs. Propranolol pretreated dogs (N = 9) displayed a significantly lower left ventricular peak positive rise in ventricular pressure (dP/dt), heart rate, and rate-pressure product throughout the experiment compared with the control group (N = 15). Subendocardial percent segment shortening as measured by sonomicrometry recovered to 65.4 +/- 7.2% of the preocclusion level after pretreatment with propranolol, whereas the control group recovered to only 11.1% +/- 10.2% after 3 hours of reperfusion. To ascertain the beneficial role of a lower heart rate on the recovery of regional contractile function, a third group of dogs (N = 6) was pretreated with propranolol, but heart rate was maintained at control levels by atrial pacing. The beneficial effects of pretreatment with propranolol were abolished in this group. There were no differences between groups in myocardial perfusion in the normal region as measured by the radioactive microsphere technique. However, in postischemic, reperfused myocardium, there was a significantly higher blood flow to subepicardium, mid-myocardium, and subendocardium after reperfusion in the propranolol-pretreated, unpaced group. Thus long-term oral pretreatment with propranolol enhances the contractile recovery of postischemic, reperfused myocardium. This protective effect of beta adrenergic blockade is primarily related to the reduction in heart rate and enhanced perfusion in the postischemic region. PMID- 2929398 TI - Relationship of functional recovery to scar contraction after myocardial infarction in the canine left ventricle. AB - We have previously reported that regional wall motion abnormalities in a canine model of acute myocardial infarction may show substantial improvement in the first 6 weeks after infarction. To determine whether the mechanism of this improvement in function is the result of scar contraction within the infarct, we studied the relationship between changes in regional wall motion defined by cross sectional echocardiography and the regional concentration of radioactive microspheres injected immediately before coronary occlusion and sampled 6 weeks after occlusion. Eight dogs underwent serial echocardiographic and microsphere blood flow measurements immediately before and 30 minutes, 48 hours, 1 week, 3 weeks, and 6 weeks after ligation of the left anterior descending or the left circumflex coronary artery. Wall motion and blood flow were measured in the short axis section of the left ventricle at the level of the midpapillary muscle in each 10-degree radial segment around the circumference of the ventricle. Infarct histology was assessed at 6 weeks by means of the same radial coordinate system. Control data were collected in a similar manner from four dogs that underwent sham operations and had no histologic evidence of infarction. In all of the animals with infarcts, but not in the sham animals, the calculated preocclusion endocardial and epicardial blood flow values in the histologic infarct zone (252 +/- 44 and 168 +/- 17 ml/min/100 gm, respectively, mean +/- SEM) were significantly higher than those in the normal opposite wall (endocardial: 106 +/- 3 ml/min/100 gm, p less than 0.01); epicardial: 108 +/- 3 ml/min/100 gm, p less than 0.01. The location and circumferential extent of myocardium showing this elevation of preocclusion blood flow correlated well (r = 0.93, p less than 0.001) with the location and circumferential extent of the histologic infarct. The amount of wall motion abnormality, measured from the "correlation plot area," decreased significantly from its maximum value of 39 +/- 3 degrees at 48 hours after coronary occlusion to 3 +/- 1 degrees (p less than 0.001) at 6 weeks after occlusion. The ratio of the preocclusion transmural blood flow in the infarct zone to that in the noninfarct zone, a measure of the condensation of the microspheres injected before coronary occlusion, and therefore of the degree of scar contraction at 6 weeks, correlated well (r = 0.83, p less than 0.01) with the recovery of wall motion 6 weeks after infarction.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2929397 TI - Protective effect of the specific thromboxane receptor antagonist, BM-13505, in reperfusion injury following acute myocardial ischemia in cats. AB - The ability of BM-13505, 4-[2-(4-chlorobenzenesulfonylamino) ethyl]-benzene acetic acid), a specific thromboxane/endoperoxide receptor antagonist, to protect the myocardium against ischemia and reperfusion injury, was assessed in an anesthetized cat model. Cats were rendered ischemic by left anterior descending (LAD) coronary artery ligation for 1 1/2 hours followed by reperfusion for 4 1/2 hours. BM-13505 or its vehicle (i.e., Na2CO3) was administered intravenously 30 minutes before reperfusion at a rate of 1 mg/kg followed by 1 mg/kg/hr. BM-13505 significantly (p less than 0.001) reduced the area of ischemic tissue as a percent of total left ventricular mass and total area at risk, without altering basic hemodynamics (i.e., arterial blood pressure, heart rate, or their product) and thereby not influencing myocardial oxygen demand. The mechanism of the protective effect of the thromboxane receptor antagonist appears to be cytoprotective but may involve the prevention of neutrophil-induced cellular damage. PMID- 2929399 TI - Variceal transformation of the subendocardial microvasculature in regions of chronic myocardial ischemia. AB - The nature and cause of the striking regional dilatation of the microvasculature of the subendocardial myocardium seen in some patients with ischemic heart disease are unknown. To examine this question, we reviewed nine patients in whom regions of the left ventricular free wall had marked prominence of subendocardial vasculature on postmortem arteriography. All hearts had severe diffuse atherosclerosis of major epicardial coronary arteries. Histologic findings, including serial transmural sections, showed extreme dilatation of arterioles, capillaries, and venules of the subendocardial third of the myocardium. In this same region myocytes showed atrophy, vacuolization (a marker of chronic ischemia), and small foci of necrosis and fibrosis. The generalized small-vessel dilatation with adjacent ischemic myocytes makes it improbable that the vascular changes are caused by collateral flow. Previous anatomic studies have shown artery-vein arrangements in the myocardium providing for countercurrent regulation of regional blood flow. This mechanism, which produces vascular enlargement on the basis of metabolic need, may explain the regional variceal transformation of the subendocardial microvasculature seen with chronic ischemia. PMID- 2929400 TI - The effect of thromboxane inhibition on vulnerability to ventricular fibrillation in the acute and chronic feline infarction models. AB - Inhibition of the enzyme that synthesizes thromboxanes may protect against the development of ventricular fibrillation (VF) during acute myocardial ischemia. This study was carried out to test this hypothesis with a new thromboxane synthetase inhibitor, and to extend the studies to alternative animal models of myocardial infarction. In a series of acute experiments, 19 cats were pretreated with 10 mg/kg of U-63557A (a dose that produced greater than 75% reduction in thromboxane B2 [TxB2] levels) or saline before abrupt left anterior descending coronary artery occlusion. Seven of the nine control animals suffered spontaneous VF associated with a 77% fall in VF threshold compared with the treated animals, of which 2 of 10 had spontaneous VF and in which VF threshold fell by only 45% (p less than 0.025). Despite a similar extent of TxB2 inhibition in another set of nine animals, U-63557A failed to protect against a fall in VF threshold during coronary reperfusion. Finally, chronic changes in VF threshold and inducibility of sustained ventricular tachycardia by programmed stimulation were assessed in a group of eight animals. The lowering of VF threshold and inducibility of ventricular tachycardia seen in the control state were not influenced by treatment with U-63557A. Thus protection against infarct-related VF by TxB2 inhibition is a property shared by more than one pharmacologic agent. Arrhythmias generated by reperfusion or induced in a more chronic setting may not be thromboxane-dependent. These results have important implications for the planning of studies designed to assess the antiarrhythmic potential of drugs that inhibit thromboxane synthesis. PMID- 2929401 TI - Repolarization interactions between cardiac segments of varying action potential duration. AB - We studied interactions between action potential duration (APD) disperse zones using a double compartment bath in which an APD lengthening solution (Ni++ 2 mmol/L, in Tyrode's solution) was added to one compartment (which contained a portion of the fiber labeled "segment A") followed by addition of an APD shortening solution (6 to 10 mmol/K+) to the other compartment ("segment B"). Standard microelectrode techniques were used in canine Purkinje fibers. With Ni++ in segment A, there was a dispersion in APD measured at both 50% (APD50) and 95% (APD95) of repolarization. After selective addition of K+ to segment B, APD50 dispersion remained constant while APD95 dispersion increased, which indicated a change in the slope of repolarization, a factor with possible arrhythmogenic potential. In addition, a characteristic transitional action potential was seen adjacent to the partition. This had a timely and normally sloping early repolarization followed by a much more gradually sloping shelf. Premature action potentials arising during this shelf had diminished upstrokes. Results of these experiments may be useful in evaluating APD dispersion in relation to arrhythmias. PMID- 2929402 TI - ECG left anterior fascicular block reveals diverse patterns on scintigraphic phase analysis. AB - Left anterior fascicular block (LAFB) remains an uncertain diagnosis by scalar ECG, particularly with coexisting inferior infarction. To assess the use of phase analysis in LAFB, left ventricular phase and amplitude maps were evaluated in the 70-degree left anterior oblique projection in eight control patients and 13 patients with LAFB who met the ECG criteria of Warner et al. The left ventricular region was divided into anterior (A) and inferior (I) segments. Contraction patterns were assessed by examination of the sequence of phase angles (phi), relative contraction time of the anterior versus inferior segments was assessed from the difference between segment mean phase angles, delta phi A-I, determined from the phase histogram, and duration of contraction was assessed by histogram width. Relative stroke volume was assessed on the amplitude image. Eight control subjects had normal amplitude, contraction of the anterior before inferior segment, narrow histogram width, and a normal ECG. Among the 13 patients with ECG LAFB, seven were concordant, with phase analysis demonstrating anterior contraction delay. Two of seven patients had narrow histograms and normal amplitude, which were compatible with isolated anterior conduction delay, and five of seven patients had broad histograms and reduced anterior amplitude, compatible with anterior infarction. Phase analysis was discordant with ECG LAFB diagnosis in six patients. All showed contraction of anterior segments before inferior segments as in normal subjects. Four had broad histograms and reduced inferior amplitude, compatible with prior inferior infarction without LAFB, and two had normal phase and amplitude maps. Phase patterns appear characteristic of LAFB with or without associated infarction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2929403 TI - Effects of verapamil on left ventricular relaxation and filling dynamics in coronary artery disease: a study by pulsed Doppler echocardiography. AB - The effect of verapamil on left ventricular diastolic function in coronary artery disease was assessed by Doppler echocardiography of transmitral flow velocities in 20 patients. At baseline, isovolumic relaxation time was prolonged compared with that in 18 age-matched normal subjects (95 +/- 13 msec versus 74 +/- 12 msec, p less than 0.001), but decreased to 80 +/- 14 msec (p less than 0.001) after treatment. The ratio between early and atrial-induced transmitral velocities (E/A-ratio) at baseline was lower in patients than in normal subjects (1.1 +/- 0.2 versus 1.4 +/- 0.3, p = 0.01), as was the filling fraction of the first third of diastole (43% +/- 5% versus 50% +/- 4%, p less than 0.001). Verapamil treatment increased the E/A-ratio to 1.3 +/- 0.4 (p less than 0.001) and filling fraction to 45% +/- 4% (p = 0.055) because of increased early filling. No change in systolic performance or heart rate was observed. Thus, coronary artery disease was associated with retarded relaxation and impairment of early filling. However, verapamil treatment enhanced relaxation and induced a filling shift toward early diastole, which indicated improved diastolic performance. The changes probably reflected reduced myocardial ischemia. PMID- 2929404 TI - Recently diagnosed idiopathic dilated cardiomyopathy: incidence of myocarditis and efficacy of prednisone therapy. AB - Fifty-two patients with recently diagnosed idiopathic dilated cardiomyopathy were studied to determine the incidence of myocarditis; patients were randomly assigned to receive either conventional therapy alone or conventional therapy plus prednisone to assess possible therapeutic efficacy with regard to survival. Inflammatory criteria were present in 23% of the population studied with 13% having overt myocarditis according to the Dallas criteria. The addition of prednisone to conventional therapy did not improve survival in a homogeneous population with new-onset dilated cardiomyopathy. Furthermore, the diagnosis of myocarditis by endomyocardial biopsy did not influence 2-year survival once dilated cardiomyopathy had developed. Biopsy-documented myocarditis resolved in all patients, according to results of 3-month follow-up endomyocardial biopsies, regardless of treatment group. There was a trend for patients with a left ventricular ejection fraction less than 20% to show reduced survival at 2 years compared to the group with a higher ejection fraction (p = 0.07). Right ventricular dysfunction determined at catheterization was present in 20 of 52 patients and was the most significant predictor of survival. Patients with preserved right ventricular function had a 95% 24-month survival rate compared to 47% for patients with right ventricular diastolic dysfunction (right ventricular end-diastolic pressure greater than or equal to 11 mm Hg) (p = 0.005). PMID- 2929405 TI - Regional distribution of lung perfusion and ventilation in patients with chronic congestive heart failure and its relationship to cardiopulmonary hemodynamics. AB - To study the relationship between the distribution of pulmonary blood flow, pulmonary ventilation, and pulmonary capillary wedge pressure, we studied six patients with chronic congestive heart failure (CHF) (New York Heart Association classes II and III) at rest and during exercise. We used krypton 81m (81mKr) and technetium 99m (99mTc) to assess lung ventilation and perfusion at rest and during exercise. Hemodynamic measurements were obtained with a balloon floatation thermodilution catheter. At rest, the upper lung zones of patients with CHF received significantly higher proportions of the blood flow compared with previously published data in normal volunteers. During exercise, however, the fractional perfusion to apices did not change, which suggests that apical flow redistribution is already maximized at rest. Measured pulmonary capillary wedge pressure failed to correlate with the upper zone or the ratio of upper-to-lower zone perfusion counts. Our findings suggest that upper zone flow redistribution may be associated with high, normal, or low capillary wedge pressure and therefore does not correlate with the pulmonary capillary wedge pressure in patients with chronic CHF. PMID- 2929406 TI - Lipomatous encasement and compression of the heart: antemortem diagnosis by cardiac nuclear magnetic resonance imaging and catheterization. PMID- 2929407 TI - Echocardiographic appearance of a flail bioprosthetic mitral valve leaflet mimicking vegetation. PMID- 2929408 TI - Ebstein's anomaly with ventricular tachycardia: evidence for the arrhythmogenic role of the atrialized ventricle. PMID- 2929409 TI - Left ventricular myxoma simulating aortic stenosis. PMID- 2929410 TI - Proarrhythmia related to a kinetic and dynamic interaction of mexiletine and theophylline. PMID- 2929412 TI - Color flow mapping in the diagnosis of coronary artery fistula in the neonate: benefits and limitations. PMID- 2929411 TI - Left ventricular thrombus with normal left ventricular wall motion in a patient with myelofibrosis. PMID- 2929413 TI - Coronary artery-to-pulmonary artery fistula: a potential new mechanism. PMID- 2929414 TI - Garlic extract prevents acute platelet thrombus formation in stenosed canine coronary arteries. PMID- 2929415 TI - Thyrotoxicosis, atrial fibrillation, and embolism, revisited. PMID- 2929416 TI - The defibrillation threshold: how many measurements are enough? PMID- 2929418 TI - How knowing the facts about the polygraph test alters pharmacy students' attitudes. AB - This study involved the measurement, by questionnaire, of attitudes and knowledge concerning the polygraph procedure. Subjects were pharmacy students who were exposed to a 50-minute lecture about the polygraph. After the lecture, significantly fewer subjects believed that the procedure should be used to screen applicants for employment, for routine periodic honesty checks, or for investigative purposes after a theft has occurred. In addition, significantly fewer subjects felt that, as practicing pharmacists, the procedure would "protect their job" or that it was "a good thing," while more indicated that they would "fear for their job." After the lecture, significantly more respondents would refuse to take the polygraph test as part of an employment application or routine periodic test of honesty. Also, more respondents objected to the procedure on grounds of poor validity/reliability, or ethical/legal grounds, and significantly more said the procedure should be outlawed. No significant difference was detected in the number of respondents who would be angry and resentful, or in the number who reported "not caring one way or the other," or in the number who would object if they were requested to undergo a polygraph exam as a practicing pharmacist. Almost all respondents did care and did object before and after the lecture. PMID- 2929417 TI - Sexual harassment in the workplace: an overview of legal issues for pharmacists. PMID- 2929419 TI - Compliance packaging: a patient education tool. AB - As a direct response to the profound negative impact that the high rate of noncompliance is having on therapeutic efficacy and total health-care costs, some pharmaceutical manufacturers have taken steps to develop compliance packaging for some products prescribed for ambulatory patients. The purpose of compliance packaging is to serve as a patient-education tool for health professionals and to make it easier for patients to remember to take their medications correctly at home. The ideal compliance package will be developed according to patient education guidelines. Compliance packaging holds promise as a significant patient education tool when health professionals combine it with personalized patient counseling and well-written medication instructions. Well-controlled cost effectiveness studies are needed to determine the impact of compliance packaging on reducing total health-care costs. PMID- 2929421 TI - Promoting public awareness of signs of heart attack. PMID- 2929420 TI - For appearance only. PMID- 2929422 TI - MPA opposes out-of-state prescription drug distribution. PMID- 2929423 TI - Polygraphs, honesty tests, and drug screening: a threat to the integrity of a proud profession. PMID- 2929424 TI - Opening and positioning a pharmacy for success, Part 2. PMID- 2929425 TI - The effect of autocorrelation on the estimation of workers' daily exposures. AB - Daily 8-hr time-weighted average (TWA) measurements may not be independent since production rates, maintenance schedules, work practices, and ventilation can result in trends where consecutive values are correlated (autocorrelation). A sampling program which involves collection of measurements on consecutive days, therefore, can result in biased estimates of the mean and variance of the exposure distribution if a high degree of autocorrelation exists. Three simulated data sets were examined to assess the effects of autocorrelation on the estimation of exposure distributions. Results indicated that about 30% of estimated mean values from a highly-autocorrelated series were outside the 95% confidence interval observed for an uncorrelated series. Three data sets obtained from actual workplaces were found to have relatively little autocorrelation. This suggests that for workplaces such as those analyzed here, a random sampling program may not be necessary, and sequential sampling may produce accurate estimates of the parameters of the exposure distribution. PMID- 2929426 TI - Investigation of organic aerosols generated during sugar beet slicing. AB - A description is given of a hygiene investigation made to determine workers' exposure to airborne microorganisms and antigen in the slicing area of a sugar beet refinery following complaints by the workers of work-related respiratory symptoms. Dust concentrations in the slicing area were not high (up to 3.5 mg/m3), but there were many airborne microorganisms (200,000 colony forming units/m3), mostly gram-positive bacteria. Of 15 workers, 7 had precipitins to a sugar beet extract. Of these 7, there were 5 who also had precipitins to an extract of dust collected on a 'Staplex' filter. There was a line of identity between the beet and dust extracts, indicating the dust contained appreciable quantities of beet antigen. As a result of these findings, local exhaust ventilation was installed before the next slicing season. Further investigations were made near the beginning and end of this second season. The results showed lower dust concentrations and markedly fewer numbers of airborne bacteria. Although total numbers of bacteria fell, numbers of gram-negative bacteria increased and, at the end of the season, comprised 20% of the total bacterial numbers. Specific immunoglobulin G (IgG) concentration in the workers' serums fell between the two slicing seasons and then remained constant through the next slicing season. This reflected the environmental measurements that showed lower dust concentrations after the installation of exhaust ventilation equipment. PMID- 2929427 TI - Clinical pulmonary function tests as predictors of work performance during respirator wear. AB - The Occupational Safety and Health Administration (OSHA) mandate requiring medical information for respirator users provides the physician with little or no guidance as to what objective criteria may be valuable in assessing the worker's ability to use a respirator safely. Therefore, the purpose of this study is to use the results of clinical pulmonary function testing to predict performance time on maximal- and endurance-type exercise tests. Respirator mask wear reduced clinical pulmonary function measures from 7%-15% from mouthpiece controls. The resistances of the mask reduced forced vital capacity by an average of 11.6% (0.65 L); forced expiratory volume in 1 sec by 7.3% (0.33 L); and maximum voluntary ventilation in 15 sec by 7.4% (12.4 L/min). Stepwise linear regression analysis was used to determine the clinical pulmonary function measures that were the best predictors of work performance. The MVV.25 with the respirator was determined to be the best predictor of maximal exercise performance both with and without the respirator. The difference in peak inspired flow with and without the respirator was the best predictor of performance time with the respirator during the endurance walk to exhaustion. Recommendations are made to the physician for procedures for determining a worker's pulmonary capacity and calculating the effect of the respirator in reducing that capacity. This information then will allow the physician to determine safe levels of ventilation for a particular work task. PMID- 2929428 TI - Physical performance during combinations of hypercapnic, resistive, and hot air breathing. AB - Performance time for a 3.2-km (2-mi) run at maximal voluntary speed was determined for 12 subjects under seven experimental conditions: resistance breathing (R), hypercapnia (C), hot air breathing (H), and combinations R + C, R + H, H + C, and R + H + C. The tests were performed on a treadmill at 5% grade. Performance time was increased significantly when the subjects were exposed to resistance breathing alone (9%) or to any combination condition containing resistance (16%-31%). The effect of breathing resistance was not specific to the presence or absence of C, H, or their combination. Nevertheless, the physiological effects were not additive and could not be predicted by knowing the effects of the individual stresses. Performance time also was increased in Condition H + C (9%). Pulmonary ventilation was the most affected physiological variable, significantly reduced in Conditions R, H, C + R, H + R, and H + C + R. In conclusion, a multistress approach should be used when determining physiological responses or performance limitations brought about by real or simulated industrial respirator-wear conditions. PMID- 2929429 TI - Investigation of charcoal cloth as a sorbent for integrated sampling of solvent vapors in mixed-expired breath using a new stainless steel sampler. AB - A stainless steel device for integrated sampling of solvents present in mixed expired breath is described. During sampling, the subject inhales breathing air through commercial charcoal inhalation canisters. Exhaled breath is sampled from the mainstream using 45-mm wafers of charcoal cloth or from the sidestream on other sorbents. The device concentrates trace contaminants present in large volumes of breath. The charcoal cloth sorbent was evaluated for sampling and analysis of m-xylene and 1,1,1-trichloroethane under simulated physiological conditions. These samples were collected from atmospheres of either analyte generated at 35 degrees-40 degrees C and 80%-90% relative humidity to simulate an exhaled breath sample matrix. Concentrations sampled ranged from 2.2 to 190 mg/m3 for 1,1,1-trichloroethane and from 0.44 to 35.6 mg/m3 for m-xylene. Volumes sampled ranged from 10 to 50 L. The m-xylene samples were collected using a 3 wafer front and a 2-wafer backup bed of charcoal cloth; 1,1,1-trichloroethane samples were collected using a 10-wafer front and a 1-wafer backup bed. All samples were desorbed in carbon disulfide and analyzed via gas chromatography using a flame ionization detector. The volume of desorption solvent ranged from 1.7 to 2.5 mL per wafer of cloth. The quantitation limit is estimated to be 2.0 micrograms/L for 1,1,1-trichloroethane and 0.4 micrograms/L m-xylene for a 50-L sample. At least 80% recovery was obtained for m-xylene or 1,1,1-trichloroethane samples stored from 1 to 14 days after collection, if the samples were refrigerated at 0 degrees C after an initial 7-day storage period at room temperature. The recovery of hexane, 1-hexene, ethyl acetate, isopropanol, methylene chloride, and methyl isobutyl ketone from the charcoal cloth also has been investigated and is reported. With the exception of isopropanol, all analytes were recovered quantitatively from the charcoal cloth by desorption with carbon disulfide following storage for 1 to 17 days at ambient temperatures. PMID- 2929430 TI - Effects of pressure-demand respirator wear on physiological and perceptual variables during progressive exercise to maximal levels. AB - Current regulations governing the certification of respiratory protective devices are based on data published in the early 1950s. The limited data base of this early work and documented increases in the average height of the population underscore the need for additional information concerning the parameters of certification. In the present study, a protocol using an inclined treadmill (0.5% grade every 12 sec) was used to test a heterogeneous population (n = 38). Through submaximal up to and including maximal exercise levels with and without respirator wear, maximal oxygen uptake (VO2max) was significantly greater (p less than 0.01) with the respirator (44.11 +/- 1.3 mL/kg.min) than without the respirator (42.18 +/- 1.4 mL/kg.min) while maximal ventilation volumes (VEmax) were not significantly different (with = 118.7 +/- 4 L/min; without 119.6 +/- 5 L/min). While peak inspired flows (PFI) with the respirator (268 +/- 7 L/min) were less than without the respirator (281 +/- 9 L/min), p greater than 0.05, the lower peak expired flow (PFE) with the respirator (289 +/- 12 L/min) than without the respirator (324 +/- 13 L/min), p less than 0.01, indicated a significant blunting effect of the respiratory flows by the expired resistance during exercise to maximal levels. Peak inspired pressures (PPi) with and without the respirator were not significantly different (p greater than 0.05). The negative values obtained within the facepiece of the respirator (-7.65 +/- 0.8 cmH2O), however, indicate that the positive pressure within the facepiece was lost, and respiratory protection may be compromised. Peak expired pressure with the respirator (13.05 +/- 0.7 cmH2O) was significantly greater than without the respirator (10.7 +/- 0.5 cmH2O) indicating that, despite a lower PFE, greater force was required to overcome the resistances of the respirator on expiration. The dyspnea index, an index of physiological effort; suggests that the subjects were working at a higher percentage of their respiratory reserve with the respirator (p less than 0.05) than without. Perceptually, subjects also felt that breathing with the respirator was more difficult (p less than 0.05). The maximum heart rate and the ratings of perceived exertion were not significantly different between the two tests at maximal exercise levels. Maximum oxygen uptake was considered reached when subjects attained a respiratory exchange ratio of at least 1.15, when a heart rate response at or greater than age-predicted maximum was achieved, when ratings of perceived exertion indicated exhaustion, and/or when the measure of VO2 had plateaued during the final minute of exercise.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2929431 TI - A graphical method to determine the uptake of nuclides by workers. AB - A method is presented which simplifies the estimation of the uptake, retention, and elimination of radioactive or stable nuclides following instantaneous ingestion or inhalation. A graph can be presented which shows the time-related presence of the element in organs of interest. It is not necessary to go back to the original differential equations used in the metabolic models or to resort to the publications which present their solutions. A glance at a graph and some simple calculations will allow the health professional to make the required determinations. PMID- 2929432 TI - Reducing workers' dust exposure during bag stacking in enclosed vehicles. AB - The Bureau of Mines has evaluated cost effective systems to ventilate enclosed vehicles being loaded directly with bagged product material at mineral processing plants. This evaluation included both forms of transportation: railcars and trailer trucks. The goal of this research was to lower the dust exposure of workers stacking bags in these enclosed vehicles; these workers usually have the highest dust exposures in the entire processing plant. The problem occurs because there is no mechanical ventilation inside these vehicles. As the vehicle is being loaded, dust concentrations increase to substantial levels because released dust has no means of exiting the vehicle or of being diluted with fresh air. In cases where the dust is hazardous, as with silica sand, this may present a serious health hazard. This research project was a two-step effort. The first step was a qualitative laboratory evaluation performed in a railcar to compare different types of ventilation systems (blowing, exhaust, and push-pull systems) using a methane (CH4) tracer gas technique. An exhaust system located over the snake conveyor was the most effective system at reducing gas levels in and around the bag stacker's work area. The second step then involved a field evaluation at a silica sand processing plant to determine the system's effectiveness in the actual work environment. Three different versions were evaluated in an attempt to optimize the exhaust ventilation system's effectiveness. The most effective version involved exhausting 54.5 m3/min (2000 ft3/min) through a fiberglass tube located 1.1 m past the end of the slinger at a 2.0-m height so as not to interfere with the bag stacker's job function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2929433 TI - Factors associated with persistent and transient fascicular blocks in anterior wall acute myocardial infarction. AB - To determine the factors associated with persistent and transient fascicular blocks, 144 patients with Q-wave anterior wall acute myocardial infarction (AMI) were studied. Thirty-three patients had new onset of fascicular block considered to be a consequence of AMI. Multivariate analysis using 16 clinical variables revealed that the number of asynergic segments, serum potassium level and pericardial rub were significant factors related to the occurrence of fascicular block. Among the 33 patients with fascicular block, 18 had persistent (group 1) and 15 had transient (group 2) fascicular blocks. When the 2 groups with fascicular block were compared, group 1 had significantly more asynergic segments than group 2 (4.7 +/- 1.2 vs 3.7 +/- 1.6, respectively), whereas pericardial rubs were observed significantly more in group 2 (67%) than in group 1 (28%). Therefore, the inflammatory process of AMI was 1 of the mechanisms related to the occurrence of a transient fascicular block and a more extensive myocardial necrosis was associated with a persistent fascicular block. PMID- 2929434 TI - Severity of coronary artery disease among blacks with acute myocardial infarction. AB - A growing body of evidence suggests that survival after acute myocardial infarction (AMI) is considerably worse among blacks than whites. The severity of coronary artery disease (CAD), as measured by the number of diseased vessels and the degree of left ventricular dysfunction, is the major determinant of survival after AMI. To determine whether or not the severity of CAD could explain the poor prognosis in a cohort of blacks followed at this institution, cardiac catheterization was performed in a consecutive series of 51 patients less than 70 years of age. All patients were studied within 2 weeks after AMI. The mean age of the patients was 56 +/- 8 (mean +/- standard deviation) and 71% were men. A greater than or equal to 50 narrowing in 0, 1, 2 or 3 coronary arteries was noted in 5, 24, 40 and 31%, respectively. Left main stenosis was present in 3 patients (6%) and the mean left ventricular ejection fraction was 55%. In a subgroup of 20 patients echocardiographic estimates of left ventricular mass/height yielded a mean of 196 g/m, and left ventricular hypertrophy on echocardiogram was present in 74%. These data indicate that among blacks with AMI in this series CAD was only modestly more severe than expected and suggest that other factors most likely explain the high mortality in blacks after hospital discharge. PMID- 2929435 TI - Prognostic significance of a low peak serum creatine kinase level in acute myocardial infarction. AB - To assess the prognostic significance of a low peak creatine kinase (CK) level, 723 consecutive patients admitted with acute myocardial infarction (AMI) within 16 hours after onset of symptoms were studied. Thrombolytic therapy was not attempted during the study. Patients were dichotomized according to their peak CK levels, determined from a cluster analysis of peak CK distribution among the population of patients who died within 3 years after hospital discharge. The 139 patients with low peak CK (less than or equal to 650 IU/liter) (group 1) were compared to the 584 patients with high peak CK (greater than 650 IU/liter) (group 2). Patients in group 1 were older and had a higher incidence of previous AMI, angina pectoris before AMI and non-Q-wave AMI. Despite a lower incidence of in hospital complications and a nonsignificantly lower hospital mortality rate (4 vs 9%) the group 1 three-year posthospital mortality rate was higher (26 vs 17%; p less than 0.02), especially in the subgroup of patients with a Q-wave infarct (mortality 31% in group 1 vs 16% in group 2; p less than 0.001). Among the 491 patients who had a first Q-wave AMI, 55 had a peak CK less than or equal to 650 IU/liter. Compared to the 436 patients with a higher peak CK, these 55 patients had a higher incidence of early postinfarction angina (31 vs 14%; p less than 0.01), a similar hospital mortality (4 vs 7%) but a higher 3-year posthospital mortality (23 vs 12%; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2929436 TI - Effects of nisoldipine on systemic and leg blood flow, oxygen transport and metabolism, and hemodynamics during exercise in effort angina pectoris. AB - The acute effects of 10 mg of oral nisoldipine on hemodynamics, oxygen transport and metabolism, and distribution of cardiac output, at rest and during semiupright bicycle exercise, were evaluated in 10 men with effort angina receiving long-term beta 1 blockade. Cardiac output and leg blood flow were measured using the thermodilution technique. At rest, nisoldipine decreased systemic resistance from 18.9 +/- 1.0 to 15.9 +/- 1.2 dynes.s.cm-5.10(2) (p less than 0.05) and cardiac output increased from 4.8 +/- 0.2 to 5.3 +/- 0.3 liters/min (p less than 0.05) without changing leg blood flow. During maximal exercise with nisoldipine, systemic resistance was reduced (10.6 +/- 0.9 to 8.6 +/- 0.5 dynes.s.cm-5.10(2), p less than 0.05) and cardiac output increased 18% (10.3 +/- 0.7 to 12.2 +/- 0.6 liters/min, p less than 0.05) when compared with control values. Exercise heart rate was higher with nisoldipine (113 +/- 4 vs 106 +/- 4 beats/min, p less than 0.01), but the mean arterial pressure was not significantly changed, giving a higher rate-pressure product. The increase in mean pulmonary artery wedge pressure was attenuated (26 +/- 3 vs 30 +/- 3 mm Hg during control exercise, p less than 0.05), but ST depression was unaltered. Exercise leg flow was reduced by nisoldipine from 4.3 +/- 0.4 to 3.9 +/- 0.3 liters/min (p = 0.07) and the proportion of cardiac output distributed to the legs was reduced from 42 +/- 3 to 33 +/- 3% (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2929437 TI - Localization of coronary artery narrowings by applying R-wave amplitude correction to exercise-induced ST depression in angina pectoris and single-vessel coronary artery narrowing. AB - This study investigated whether coronary artery narrowings can be localized by applying R-wave amplitude correction to exercise-induced ST depression in multiple unipolar precordial lead electrocardiography using 20 electrodes covering the left chest wall. Ten normal subjects and 29 patients with stable angina pectoris and single-vessel coronary artery narrowing (greater than or equal to 75% luminal diameter stenosis in only 1-vessel) participated. Of the 29 patients, 5 had left main coronary artery disease (CAD), 14 had left anterior descending CAD, 4 had right CAD and 6 had left circumflex CAD. The exercise induced ST depression with R-wave amplitude correction was defined as the exercise-induced ST depression divided by the R-wave amplitude. The 20 points of the lead system were divided into 4 areas: the left main, left anterior descending, right and left circumflex coronary arteries. Coronary artery narrowing was supposed to be in an artery corresponding to the area where the maximal value of the exercise-induced ST depression with and without R-wave amplitude correction was situated. By applying R-wave amplitude correction, the diagnostic ability of localization of coronary artery narrowings was improved significantly from 52% to 86% (p less than 0.005). In particular, localization of the left main coronary artery narrowing was correctly diagnosed in 100% (5 of 5) of angina pectoris patients with left main CAD. PMID- 2929438 TI - Effects of disopyramide on cycle length, effective refractory period and excitable gap of atrial flutter, and relation to arrhythmia termination by overdrive pacing. AB - The administration of class IA antiarrhythmic drugs facilities termination of atrial flutter by overdrive pacing. To investigate the electrophysiologic determinants of this effect, changes in the cycle length, the effective refractory period and the excitable gap of spontaneous type I atrial flutter were studied in 11 patients given intravenous disopyramide (3 mg/kg in 1 hour). After drug infusion, the cycle length of atrial flutter increased from 238 +/- 26 to 298 +/- 38 ms (+25%; p less than 0.001) and the effective refractory period prolonged from 169 +/- 19 to 192 +/- 25 ms (+14%; p less than 0.01). The excitable gap prolonged from 62 +/- 16 to 96 +/- 27 ms (+55%; p less than 0.001). Atrial flutter was terminated by overdrive pacing (mean cycle 203) in 10 of 11 patients; in 1 patient atrial fibrillation resulted after high rate stimulation. In the setting of an anatomically defined reentry circuit, as in type I atrial flutter, the administration of disopyramide prolongs both cycle length and refractory period. The finding of an increased excitable gap suggests that the drug exerts its prominent effect by depressing conduction velocity. A wider excitable gap allows easier penetration of the stimulus in the reentry circuit and accounts for the beneficial effects of type IA antiarrhythmic drugs on the termination of atrial flutter by overdrive pacing. PMID- 2929439 TI - Signal-averaged electrocardiography in the time and frequency domains. AB - The noninvasive signal-averaged electrocardiographic detection of late potentials correlates with the spontaneous occurrence of sustained ventricular tachycardia (VT). Frequency analysis of the electrocardiographic signal from the terminal QRS and ST segment also correlates with sustained VT. This study was designed to compare these 2 methods by analysis of signals recorded from the same hardware system. Signals were recorded from 234 patients with prior myocardial infarctions with a commercially available signal-averaging system. Patients were classified into 2 groups: group 1 consisted of 84 patients with VT and group 2 consisted of 150 patients without VT. In the frequency domain, magnitude and energy area ratios and peak ratios of the spectral plot from 20 to 50 Hz over 0 to 20 Hz were calculated for a 140-ms interval starting 60 ms after the beginning of the QRS. In the time domain, the duration of the filtered QRS was 121 +/- 29 ms for group 1 and 110 +/- 25 ms for group 2 (p less than 0.002). The duration of the terminal QRS less than 40 microV was 45 +/- 21 ms in group 1 and 36 +/- 18 ms in group 2 (p less than 0.001). The root-mean-square amplitude of the terminal 40 ms of the QRS was 25 +/- 24 microV in group 1 and 36 +/- 33 microV in group 2 (p less than 0.004).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2929440 TI - Comparison of exercise performance of six rate-adaptive right ventricular cardiac pacemakers. AB - Single chamber cardiac pacemakers capable of automatically adjusting the rate according to body requirements have become an important means of physiologic pacing in patients with bradycardias. Such pacemakers are dependent on a nonatrial sensor of physiologic needs to optimize the rate response. Fifty rate adaptive right ventricular pacemakers were implanted in 46 patients with a mean age of 60 +/- 4 years (mean +/- standard error of the mean). There were 2 types of activity-sensing pacemakers (Activitrax and Sensolog 702), the QT-sensing pacemakers (TX2 and Quintech), 2 types of respiratory-sensing pacemakers (Biorate [RDP3 and MB1] and Meta) and a rate-adaptive pacemaker that senses right ventricular dP/dt (Deltatrax). The rate responses of a group of 9 volunteers of similar age (62 +/- 2 years) were also included for comparison. Improvement in exercise duration in the rate-adaptive mode compared to the constant-rate ventricular pacing (VVI) mode was achieved during randomized symptom-limited treadmill exercise (from 26 to 49%). Compared with the sinus responses, the activity-sensing pacemakers responded most appropriately in speed. However, their rate responses were not related to workload and had lower correlations with estimated oxygen consumption (r = 0.7 and 0.47 for Activitrax and Sensolog, respectively). Respiratory-sensing pacemakers responded more appropriately in magnitude (r greater than 0.8) although their rate responses were slower. All pacemakers studied either showed no response or a reverse-rate response to the Valsalva maneuver. It is concluded that the currently available rate-adaptive ventricular pacemakers improve exercise performance compared with VVI pacemakers in patients with bradycardias.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2929441 TI - Effect of dobutamine on plasma potassium in congestive heart failure secondary to idiopathic or ischemic cardiomyopathy. AB - Dobutamine was administered in a dose of 10 +/- 1 micrograms/kg/min to 13 patients with severe idiopathic or ischemic dilated cardiomyopathy. Acute hemodynamic improvement was noted in all patients. All patients had a significant decrease in plasma potassium (4.6 +/- 0.1 to 4.2 +/- 0.2 mEq/liter, p less than 0.0001) at peak infusion. The decrease in potassium persisted for at least 45 minutes after discontinuing the infusion. Three patients had exacerbation of baseline ventricular arrhythmias that resolved with infusion discontinuation. Changes in plasma norepinephrine could not explain the potassium decrease or arrhythmia production, which also significantly decreased in these patients (771 +/- 123 to 524 +/- 73 pg/ml, p less than 0.01). It is concluded that dobutamine causes a significant decrease in plasma potassium and that the decrease persists at least 45 minutes after the infusion is discontinued. PMID- 2929443 TI - Respiratory influence on right and left ventricular diastolic function in normal children. AB - Doppler echocardiograms of the tricuspid and mitral valves were recorded with electrocardiogram and respirations in 20 normal children aged 1.5 to 11 years. Four variables of early diastolic left ventricular (LV) filling decreased with inspiration: the peak E velocity (mean decrease 8%, p less than 0.0001), the ratio of E/A areas (mean decrease 12%, p less than 0.001), the peak E/A velocity ratio (mean decrease 14%, p less than 0.005) and the 1/3 area fraction (mean decrease 12%, p less than 0.001). Variables of late active atrial emptying (peak A velocity and A/total area ratio) were unchanged with respiration. There was a significant increase in the right ventricular (RV) peak E (mean increase 26%, p less than 0.0001) and peak A velocities (mean increase 18%, p less than 0.0001) and mean heart rate (5% increase) with inspiration. The enhancement of RV filling was similar for early and late diastolic filling, since each of the variables generated from their ratios were not significantly changed with inspiration. Inspiration significantly enhances RV venous return, while the LV response to inspiration is a complex interplay among preload, afterload and ventricular interdependence. Assessment of pediatric RV and LV diastolic function should include standardization for phase of respiration. PMID- 2929442 TI - Results of percutaneous mitral commissurotomy in 200 patients. AB - To assess the feasibility and efficacy of percutaneous mitral commissurotomy (PMC), the procedure was attempted in 200 patients with severe mitral stenosis. There were 154 women and 46 men, their mean age was 43 +/- 16 years (range 13 to 79) and 15 were older than 70 years of age. Forty-four had had previous surgical commissurotomy. Forty were in New York Heart Association class II, 152 in class III and 8 in class IV. In regard to valvular anatomy, 67 had calcified valves, 58 had pliable valves and only mild subvalvular disease, and 75 had flexible valves but extensive subvalvular disease. Grade 1+ mitral regurgitation was present in 62 and grade 2+ in 2. In 11 patients the procedure was discontinued because of complications in 3 and technical failure in 8. Six of the 8 technical failures occurred during the first 15 attempts. Effective PMC was performed in 189 patients using 1 balloon in 23 and 2 balloons in 166. After PMC, there was a significant improvement in mean left atrial pressure (21 +/- 7 to 12 +/- 5 mm Hg, p less than 0.0001), mean mitral gradient (16 +/- 6 to 6 +/- 2 mm Hg, p less than 0.0001), cardiac index (2.6 +/- 0.8 to 3.1 +/- 0.8 liters/min/m2, p less than 0.001) and valve area assessed by hemodynamics (1.1 +/- 0.3 to 2.2 +/- 0.5 cm2, p less than 0.0001) and 2-dimensional echocardiography (1 +/- 0.3 to 1.9 +/- 0.4 cm2, p less than 0.0001). No patient died. Embolism occurred in 8 (4%), with no further sequelae. Sixteen (8%) had atrial septal defect detected by oxymetry.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2929444 TI - Estimation of the ratio of pulmonary to systemic pressures by pulsed-wave Doppler echocardiography for assessment of pulmonary arterial pressures. AB - This study describes a method for estimation of the ratio of pulmonary to systemic pressures by pulsed-wave Doppler echocardiography. Sixty-eight patients ages 1 day to 68 years who underwent cardiac catheterization had Doppler studies of the right and left ventricular outflows. Preejection period (PEP), ejection time (ET) and mean acceleration to peak velocity (ACCm) were measured on each waveform. The expression: F = (PEP x ACCm)/ET was calculated for right and left ventricular outflows as an index of the effects that the interaction between ventricular contraction and afterload has on the shape of the Doppler waveforms generated in each outflow. The quotient of (F for the right outflow)/(F for the left outflow), or waveform contour ratio, was used to express the degree of pressure-dependent variability between each subject's right and left ventricular outflow tracings. The waveform contour ratio was strikingly similar to the ratio of systolic pulmonary to systemic pressures and also closely correlated to the ratio of mean pressures. The product of waveform contour ratio and arm systolic pressure gave a consistently accurate estimate of systolic pulmonary pressures. It is concluded that the present method can be used successfully for the noninvasive assessment of pulmonary arterial pressures. PMID- 2929445 TI - When is QT prolongation antiarrhythmic and when is it proarrhythmic? PMID- 2929446 TI - Detection of calcific deposits in coronary arteries by ultrafast computed tomography and correlation with angiography. PMID- 2929447 TI - Effects of long-acting propranolol on A.M. and P.M. peaks in silent myocardial ischemia. PMID- 2929448 TI - Eccentricities of Activitrax pulse generators. PMID- 2929449 TI - Association of the acquired bicuspid aortic valve with rheumatic disease of atrioventricular valves. PMID- 2929451 TI - Anomalies of the mitral valve and of the left ventricular architecture in tricuspid valve atresia. PMID- 2929450 TI - Angiographic classification of the isolated, persistently patent ductus arteriosus and implications for percutaneous catheter occlusion. PMID- 2929452 TI - Ashman phenomenon of the T wave. PMID- 2929453 TI - Rupture of the stomach and the esophagus after attempted transcatheter ablation of an accessory pathway by direct current shock. PMID- 2929454 TI - Defining idiopathic dilated cardiomyopathy: a courtroom discussion. PMID- 2929455 TI - Comparison of transthoracic and transesophageal echocardiography in diagnosis of left atrial myxoma. PMID- 2929456 TI - Resolution of spontaneous contrast with platelet disaggregatory therapy (trifluoperazine). PMID- 2929457 TI - Treatment of macroreentrant ventricular tachycardia with radiofrequency ablation of the right bundle branch. PMID- 2929458 TI - Pacemaker twiddler's syndrome. PMID- 2929459 TI - Value of magnetic resonance imaging for diagnosis of cervical epidural hematoma associated with anticoagulation after cardiac valve replacement. PMID- 2929460 TI - Cardiac consequences of massive acetaminophen overdose. PMID- 2929461 TI - Asymptomatic aortico-left ventricular tunnel in adulthood. PMID- 2929462 TI - Combined dipyridamole-exercise thallium imaging. PMID- 2929463 TI - Is ST elevation or T inversion the most benign acute myocardial infarction? PMID- 2929464 TI - Frequency of rupture of the left ventricular free wall or ventricular septum among necropsy cases of fatal acute myocardial infarction since introduction of coronary care units. AB - Review of 18 published reports before the widespread use of cardiac care units disclosed that the frequency of rupture of the left ventricular free wall or ventricular septum among necropsy cases of acute myocardial infarction (AMI) ranged from 4 to 24% (mean 8%) (619 of 7,905 cases). The frequency of rupture of the left ventricular free wall or ventricular septum among necropsy patients with fatal AMI studied in this laboratory since 1968 was analyzed. Of 648 such patients, 204 (31%) had rupture of the left ventricular free wall or ventricular septum. Rupture occurred in 171 (40%) of 431 patients without healed myocardial infarcts (grossly visible left ventricular scars), and in 29 (13%) of 217 patients with a healed myocardial infarct (p less than 0.01). Thus, the frequency of rupture of the left ventricular free wall or ventricular septum during AMI appears to have increased substantially since the widespread use of coronary care units. Also, the frequency of rupture is nearly 3 times greater in those in whom rupture occurred during the first AMI compared to those with a previous infarct that healed. PMID- 2929465 TI - Breathlessness, angina pectoris and coronary artery disease. AB - The relation of breathlessness to angina was examined in 7,735 middle-aged British men. Among men who did not report breathlessness, the age-standardized prevalence rate of angina was 4%. In men with mild, moderate or severe breathlessness, the prevalence rates of angina were 16, 29 and 41%, respectively. The association between breathlessness and angina was independent of age or cigarette smoking, with similar relations observed in men who had never smoked. The prevalence of electrocardiograms revealing ischemia increased with the severity of breathlessness, even in men without angina or other evidence of coronary artery disease (CAD) at screening. In men with a low forced expiratory volume in 1 second, the prevalence of angina was also increased, but the association was much weaker than that observed between angina and breathlessness. After a 5-year follow-up, 25% of men severely breathless at screening but without any initial evidence of CAD had developed angina, 5% had had a heart attack (half of these were fatal) and 7% were dead from causes other than CAD. The corresponding rates for men not breathless at screening and without evidence of CAD were: 4% angina, 2.5% heart attack and 2% dead from causes other than CAD. Breathlessness appears to be an early indicator of CAD in the absence of either angina or electrocardiographic evidence of ischemia. PMID- 2929466 TI - Cardiac arrhythmias and heart rate in hyperthyroidism. AB - The arrhythmia profile and heart rate (HR) were analyzed by 24-hour Holter monitoring in 37 hyperthyroid patients before (triiodothyronine [T3] hormone level = 331 +/- 108 ng/dl), during (T3 level = 202 +/- 98 ng/dl) and after an antihyperthyroid therapy of 8 to 89 weeks' duration (T3 level = 149 +/- 41 ng/dl). The data were compared with those of 50 control subjects free from cardiac disease. Only 12 hyperthyroid patients (32%) had complex ventricular arrhythmias (Lown grade 3 or 4) as compared with 6 normal subjects (12%, p greater than 0.05). Three patients (8%) had repetitive ventricular arrhythmias (Lown grade 4A/B) as compared with 4 normal subjects (8%, p greater than 0.05). Supraventricular premature complexes occurred more often in hyperthyroid patients than in normal subjects before and after therapy (p less than 0.001). The prevalence of supraventricular tachycardia decreased from 8 patients to 1 during therapy (p less than 0.002). The HR decreased from 95 +/- 13 to 79 +/- 9 beats/min after therapy, but was still increased as compared with the normal subjects (72 +/- 8 beats/min, p less than 0.001). A day/night difference in HR greater than 10% was found in 32 patients (86%) and was more pronounced than in the normal group (p less than 0.001). Compared with the normal HR profile, the HR curve of hyperthyroid patients was shifted to a higher level (about 20 beats/min). Serum T3 level correlated best with HR at night in hyperthyroid patients (r = 0.74, p less than 0.001). Thus, hyperthyroid patients show frequent supraventricular arrhythmias that might be reversible during therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2929467 TI - Evaluation by exercise Doppler echocardiography of maintenance of cardiac output during ventricular pacing with or without chronotropic response. AB - To examine the effectiveness of activity-initiated rate-responsive pacing, this study assessed the increases in stroke volume and cardiac output during randomized treadmill exercise in rate-responsive and fixed-rate ventricular (VVI) pacing in 10 patients. Stroke volume index and cardiac index were determined by suprasternal Doppler measurements. Compared with the findings during VVI pacing, the rate-responsive pacing was associated with (1) prolongation of exercise duration (8.0 +/- 4.0 vs 7.3 +/- 3.6 minutes, p less than 0.05); (2) greater exercise-induced positive chronotropic response (mean maximal heart rate 127 +/- 12 vs 78 +/- 15 beats/min, p less than 0.001); (3) smaller increase in stroke volume index (38 +/- 10 vs 50 +/- 11 ml/m2, p less than 0.001), and (4) greater increase in cardiac index (4.7 +/- 1.1 vs 3.9 +/- 1.0 liters/min/m2, p less than 0.001). A significant correlation was observed between age and percent increase in stroke volume index during VVI pacing (p less than 0.05). These findings indicate that VVI pacing increased stroke volume more than did rate-responsive pacing, especially in younger patients, but the increase in cardiac output was less than that seen with rate-responsive pacing due to the absence of chronotropic response. Accordingly, an activity-sensing, rate-responsive pacemaker can effectively increase the heart rate, significantly augment cardiac output and extend the duration of exercise. PMID- 2929468 TI - Echocardiographic and histologic evaluation of the right ventricle in ventricular tachycardias of left bundle branch block morphology without overt cardiac abnormality. AB - The right ventricle was investigated by multiple biopsies and detailed echocardiographic evaluation, including measurement of cavity dimensions at the level of the inflow, body and outflow tract, in 27 patients with right ventricular tachycardia who had no clinical evidence of an underlying morphologic abnormality. Nine (33%) patients had abnormal biopsy results, with a quantifiable increase in interstitial fibrosis. Abnormal echocardiograms, defined as an increase in greater than or equal to 2 dimensions of the right ventricular cavity or wall motion abnormalities or both, were seen in 9 patients. There was a strong association between abnormal myocardial histologies and abnormal right ventricular echocardiograms (p less than 0.001). An abnormal echocardiogram was 94% specific and 80% sensitive for an abnormal biopsy. The findings of echocardiography and biopsy were correlated with the electrocardiographic features of the tachycardia. Evidence of right ventricular disease was seen in all 6 patients with superior frontal plane axis of clinical tachycardia as compared with 4 of 21 with inferior axis (p less than 0.001). Thus, 2-dimensional echocardiography is a sensitive means of diagnosing right ventricular disease in patients with nonischemic tachycardias of left bundle branch block morphology. A superior frontal plane axis of ventricular tachycardia in this group strongly suggests right ventricular disease, whereas an inferior frontal plane axis is frequently not associated with any morphologic or histologic abnormality of the right ventricle. PMID- 2929470 TI - Diagnostic and prognostic utility of right-sided catheterization and endomyocardial biopsy in idiopathic dilated cardiomyopathy. AB - To determine the value of cardiac catheterization and endomyocardial biopsy in patients with heart failure and dilated cardiomyopathy, the records of 61 patients (36 men, 25 women, ages 13 to 65 years) with this disorder were reviewed. Myocardial lymphocytic infiltration was present in 8 (13%). Three had myocyte degeneration and necrosis ("definite" myocarditis), whereas the other 5 had no degeneration or necrosis ("equivocal" myocarditis). Compared with the 53 without lymphocytic infiltration, these 8 patients more often had symptoms of a preceding viral illness (88 vs 30%, p = 0.002) and had a shorter duration of cardiac symptoms (18 +/- 18 vs 109 +/- 132 days [mean +/- standard deviation], p less than 0.001). Histologic features of the biopsy did not relate to survival, but right- and left-sided intracardiac pressures were higher (p less than 0.05) in nonsurvivors. Thus, (1) endomyocardial biopsy is most likely to show lymphocytic infiltration in patients with symptoms of a preceding viral illness and a short duration of cardiac symptoms, and (2) right- and left-sided hemodynamic variables at the time of biopsy may offer insight into prognosis. PMID- 2929469 TI - Effect of endurance training on blood pressure at rest, during exercise and during 24 hours in sedentary men. AB - The effect of 4 months of physical training on resting, exercise and 24-hour blood pressure (BP) was studied using a randomized crossover design in 26 healthy, sedentary men, with an average age of 39 +/- 10 (standard deviation) years. Peak oxygen uptake increased by 14% (p less than 0.001) and the physical working capacity at a heart rate of 130 beats/min by 25% (p less than 0.001). The heart rate was reduced by 7 beats/min at night (p less than 0.01) and by 6 beats/min during the day (p less than 0.001). Training-induced changes of BP varied according to measuring conditions. A decrease in BP at rest while sitting in the morning in the laboratory was significant for diastolic (-5 mm Hg, p less than 0.01) but not for systolic BP. During exercise, systolic BP was significantly lower after training, when measured at the same submaximal workloads. However, when workload was expressed as a percentage of peak oxygen uptake, systolic BP was not different before and after training. When measured during 24 hours, the training-induced change in BP was not significant at night either for systolic or diastolic BP. During the day the decrease in diastolic BP was significant (-5 mm Hg, p less than 0.001), but the change in systolic BP was not. PMID- 2929471 TI - Doppler echocardiographic evaluation of tilting-disc prosthetic heart valves in children. AB - To determine the Doppler characteristics of tilting-disc prosthetic heart valves in children, 22 children with mitral prostheses were studied 8 +/- 2 months after surgery, and 10 children with aortic prostheses were studied 37 +/- 26 months after surgery. All valves were thought to be functioning normally by clinical examination. Valve competence was interrogated and peak and mean velocities were measured by standard pulsed wave, continuous wave and color Doppler techniques. Prosthetic valve area was calculated and compared to the known valve area. Mild prosthetic valve regurgitation was present in 8 of 22 mitral and 7 of 10 aortic prostheses. For mitral prostheses, peak velocity was 192 +/- 41 cm/s, mean velocity was 118 +/- 37 cm/s and mean gradient was 7 +/- 4 mm Hg. For aortic prostheses, peak velocity was 287 +/- 88 cm/s, mean velocity was 197 +/- 59 cm/s, peak gradient was 36 +/- 21 mm Hg and mean gradient was 19 +/- 11 mm Hg. Prosthetic mitral valve area, calculated by the pressure half-time and modified Gorlin methods, correlated well with the known valve area (r = 0.89, standard error of the estimate = 0.29 and r = 0.95, standard error of the estimate = 0.21, respectively). Prosthetic aortic valve area, calculated by the modified Gorlin method, correlated well with the known valve area (r = 0.89, standard error of the estimate = 0.18). Residual valvular abnormalities are common after prosthetic valve insertion in children. Doppler estimates of prosthetic valve area correlate well with the known valve area but have a large standard error of the estimate. PMID- 2929472 TI - Reliability of blood pressure recordings. PMID- 2929473 TI - ST elevation during exercise testing. PMID- 2929474 TI - Effects of amiodarone on the kinetics of antipyrine. PMID- 2929475 TI - Usefulness of shock wave lithotripsy as pretreatment for balloon valvuloplasty in calcified mitral stenosis. PMID- 2929476 TI - Effect of aging on peak systolic left ventricular wall stress in normal subjects. PMID- 2929477 TI - Cardiac mapping at Duke Medical Center. AB - CLINICAL PERSPECTIVE: Ventricular fibrillation is a major, but little understood, cause of death. Although defibrillation with electric shock has been in use for several decades, and although many advances have been made in the design of defibrillators (including the development of implantable devices for high-risk patients), this procedure has generally been an empiric one. The mechanisms of the procedures are being intensely studied at Duke University and other institutions in the hope of developing more energy efficient and clinically effective defibrillation equipment. PMID- 2929478 TI - Intraoperative echocardiography in congenital heart disease surgery: preliminary report on a current study. AB - CLINICAL PERSPECTIVE: The first prospective trial in which both echocardiography and Doppler color flow imaging (echo-DCFI) are used routinely during surgery for congenital heart lesions has been undertaken at Duke Medical Center. Precardiopulmonary bypass (CPB) echo-DCFI examinations have revealed previously unsuspected cardiac findings in several of the patients. These examinations have influenced the surgical course in some way in many of the cases. Post-CPB ultrasound evaluation of the quality of the surgical repairs alone has resulted in immediate additional corrective surgery in several patients, most of whom then left the operating room with an optimum repair. PMID- 2929479 TI - Kwashiorkor in North America. AB - The controversy regarding the relative importance of protein vs energy deficiency in the genesis of kwashiorkor has not been resolved by studies of protein-energy malnutrition (PEM) in developing countries. Cases of edematous PEM (n = 29) in North America on the other hand provide clear indications that protein deficiency is an essential prerequisite for the development of kwashiorkor and marasmic kwashiorkor. Energy intakes may vary from low to high and the main source of energy may be carbohydrate or fat. These findings are in keeping with experimental evidence that a low ratio of protein to energy disrupts the usual hypometabolic response to dietary deficiency and leads to hypoalbuminemia and consequent edema. Protein supplements should be a part of programs aimed at preventing kwashiorkor. PMID- 2929480 TI - Total-body electrical conductivity (TOBEC): relationship to estimates of muscle mass, fat-free weight, and lean body mass. AB - A comparison of methods for estimating body composition (BC) of 12 subjects was made by using fat-free weight from total-body electrical conductivity (FFWT), muscle mass from 3-methylhistidine excretion (MM3MH) and creatinine excretion (MMCRE), fat-free weight from hydrostatic weighing (FFWBD), and lean body mass from whole-body potassium counting (LBMK). Data were analyzed for day-to-day variability and regression analyses were applied to compare the different methods of measuring BC. Mean values (+/- SEM, kg) for the estimates were 53.9 +/- 3.5 (FFWT), 26.9 +/- 2.9 (MM3MH), 25.3 +/- 2.5 (MMCRE), 53.2 +/- 3.6 (FFWBD), and 52.8 +/- 3.5 (LBMK). Regression analyses revealed that TOBEC estimates of fat free weight had an adjusted r2 (+/- SEE, kg) of 0.95 +/- 2.2, 0.50 +/- 7.9, 0.95 +/- 1.8, and 0.88 +/- 4.0 for MM3MH, MMCRE, FFWBD, and LBMK, respectively. It was concluded that TOBEC is a potentially reliable method for estimating the muscle mass within the fat-free compartment, as well as fat-free weight and lean body mass. PMID- 2929481 TI - Weight and recumbent length from 1 to 12 mo of age: reference data for 1-mo increments. AB - Serial data from 504 infants were used to develop reference data for 1-mo increments in weight and recumbent length by fitting a family of three-parameter mathematical functions to the serial data for each individual. The percentiles for status and for increments tended to be larger for the boys than for the girls except for the lower percentiles of increments for weight after 9-10 mo and for recumbent length after 8-9 mo. These data can be used to assess growth in white or black infants whether they are breast-fed or formula-fed. These new data will allow earlier evaluation of growth velocity than the reference data for 3- and 6 mo increments that were available previously. This can lead to the earlier initiation of diagnostic procedures and treatment. The present data should be useful also in research studies. PMID- 2929483 TI - Low carnitine intake and altered lipid metabolism in infants. AB - We examined the effect of dietary carnitine on variables of lipid metabolism in human infants. Normal male full-term infants were fed an isolated soy-protein based formula with or without added carnitine from age 6-9 d to age 112 d. Growth and food intake were measured throughout the study. At ages 56 and 112 d serum concentrations of carnitine, free fatty acids, and triglycerides and urinary excretion of carnitine and medium-chain dicarboxylic acids were measured. Serum carnitine concentrations were lower in all infants fed unsupplemented formula. There was no difference in growth or food intake between the two groups of infants. Serum free fatty acid concentrations were significantly higher in the infants not receiving dietary carnitine. Moreover, excretion of all three medium chain dicarboxylic acids was significantly higher in infants not receiving dietary carnitine. We conclude that lack of dietary carnitine affects lipid metabolism of infants during the first 4 mo of life. PMID- 2929482 TI - Breast-milk composition in women with cystic fibrosis: report of two cases and a review of the literature. AB - Breast milk was collected from two women with cystic fibrosis (CF) and data from the literature was reviewed. The sodium concentration was within normal limits, 11-24 mmol/L in colostrum and 7-8 mmol/L in mature milk. Normal physiologic changes in milk composition after parturition (decreases in Na and increases in lactose) and during individual feeding periods (increases in fat and decreases in protein) were observed. Concentrations of milk protein, fat, and sugars were normal when the pulmonary disease of these patients was mild. During exacerbations of pulmonary disease, the concentrations of milk macronutrients were reduced. Milk secreted by women with CF appears to be physiologically normal, safe for the infant, and breast-feeding by mothers with CF should no longer be discouraged. Variations in the macronutrient content of CF milk warrants routine monitoring of the mother with CF and the breast-fed infant, especially during exacerbations in the pulmonary aspects of this disease. PMID- 2929484 TI - Cholesterol absorption: regulation of cholesterol synthesis and elimination and within-population variations of serum cholesterol levels. AB - Obesity and dietary plant sterols were negatively associated with fractional absorption of dietary cholesterol in a random population of 63 middle-aged men. Absorbed dietary cholesterol increased linearly with the increase of dietary cholesterol intake. The higher the fractional and absolute absorption of dietary cholesterol the lower the rates of biliary secretion, fecal elimination, and cholesterol synthesis. The findings also revealed that high serum levels of total, LDL, and HDL cholesterol were associated with high cholesterol absorption and that of HDL cholesterol was associated also with low synthesis and fecal elimination of cholesterol. Thus, cholesterol absorption efficiency and absorbed dietary cholesterol significantly regulate cholesterol synthesis and elimination and are important determinants of within-population variation in the serum levels of total, LDL, and HDL cholesterol. PMID- 2929485 TI - Protein utilization by young women consuming animal or plant protein diets at various levels of vitamin B-6 intake. AB - Eight young women consumed a vitamin B-6 depletion diet (egg albumen formula, less than 0.05 mg vitamin B-6/d) for 11-28 d. Subjects (n = 4) then consumed either animal protein (AP, mainly dairy and poultry products) or plant protein (PP, mainly various types of beans) diets with increasing vitamin B-6 intake (0.5, 1.0, 1.5, and 2.0 mg/d) for periods of 14-21 d. All diets provided 1.55 g protein/kg body wt. Apparent protein digestibility of AP (94.6%) was significantly higher than that of PP (88.4%) diets (p less than 0.001). Protein digestibility was not significantly affected by vitamin B-6 intake. Apparent nitrogen balance of subjects consuming AP diets was slightly, though not significantly, higher than that of subjects fed PP diets. N balance was not influenced by vitamin B-6 intake. Data suggest that short-term low vitamin B-6 intake does not affect protein utilization in humans as determined by digestibility and N balance. PMID- 2929486 TI - Effects of missing breakfast on the cognitive functions of school children of differing nutritional status. AB - We examined the effects of omitting breakfast on the cognitive functions of three groups of children: stunted, nonstunted controls, and previously severely malnourished. They were admitted to a metabolic ward twice. After an overnight fast half the children received breakfast on their first visit and a cup of tea the second time. The treatment order was reversed for the other half. When breakfast was omitted, both the stunted and previously malnourished groups responded similarly. The malnourished groups had lower scores in fluency and coding whereas the control group had higher scores in arithmetic. The children were divided into wasted and nonwasted groups. Wasted children were adversely affected in the digit span backwards tests, and wasted members of the malnourished groups were adversely affected in efficiency of problem solving and those in the control group in digit span forwards. These results indicate that cognitive functions are more vulnerable to missing breakfast in poorly nourished children. PMID- 2929487 TI - Elevated fasting breath hydrogen and abnormal hydrogen breath tests in children with sickle cell disease: a preliminary report. AB - Hydrogen breath tests were performed in eight children with sickle cell disease (Hgb S-S), four of whom were growth retarded. Average base-line breath H2 values after an overnight fast were elevated (22.4 +/- 10.8 ppm; normal = 7.1 +/- 5.0). Breath H2 concentrations increased significantly above base line within 30-40 min after lactulose ingestion in the four growth-retarded children whereas a negligible rise was observed in the four with normal growth indices. Breath H2 production for each time interval in the first 120 min was greater in all Hgb S-S then in normal children (p less than 0.01 for each time interval measured before 60 min). The results indicate that children with sickle cell disease have intestinal abnormalities favoring excess production of H2 in the fasted state combined with early elevations in postlactulose breath H2 in those with growth retardation. The possible role of disordered gastrointestinal motility and/or anomalously distributed intestinal flora in growth retardation of children with Hgb S-S requires further investigation. PMID- 2929488 TI - Glycemic responses in insulin-dependent diabetic patients: effect of food composition. AB - This study examined the hypothesis that the glucose component of food and not the total carbohydrate is the major determinant of the glycemic response in patients with insulin-dependent diabetes mellitus. Patients were given glucose alone, fructose alone, glucose + fructose, lactose, and glucose + fat + protein. Fructose given alone increased the blood glucose almost as much as a similar amount of glucose (78% of the glucose-alone area, p less than 0.05). However, the same amount of fructose given with glucose produced no greater glycemic response than did glucose alone (108%). Similarly, galactose contributed only slightly to the glycemic response when given as lactose (122%, p less than 0.01) whereas protein and fat had no additional glycemic effect (101%). To test the above hypothesis in natural foods, patients were fed an amount of bread (high glycemic index) or apple (low glycemic index) that contained 25 g glucose. Both challenges produced glycemic responses very similar to 25 g purified glucose. PMID- 2929490 TI - Zinc, calcium, and magnesium metabolism: effects on plasmacytomas in Balb/c mice. AB - The effects of different amounts of dietary zinc on the Zn absorption rate and on Zn, calcium and magnesium concentrations in tissues of MOPC 104E tumor-bearing Balb/c mice were determined. The Zn absorption rate was inversely related to the amounts of Zn in their diets and was lower than that of nontumor-bearing control mice fed a laboratory mice chow. Zn concentrations of tumor-bearing mice were also low compared with control mice but tumor Zn concentrations, regardless of the concentrations of Zn in the diets, were higher than those of normal tissues of the host other than the pancreas. Ca concentrations in tumor and tissues of tumor-bearing mice were higher than in control animals but Mg concentrations in tissues of tumor-bearing mice appeared to be similar to those of control mice. Results suggest that tumor-bearing mice have a lower intestinal Zn absorption capacity and a higher Zn uptake rate causing other tissues to become hypozincemic and hypercalcemic. PMID- 2929489 TI - Intestinal uptake of retinol: enhancement by bovine milk beta-lactoglobulin. AB - The effect of bovine milk beta-lactoglobulin (BLG) on intestinal uptake of retinol was examined in suckling rats with the everted sac technique. Uptake of 0.06 mumol retinol/L bound to BLG (BLG-retinol) was significantly (p less than 0.01) higher than that of 0.06 mumol free retinol/L both in the jejunum and the ileum. The enhancing effect of BLG on retinol uptake was specific because equimolar concentrations of bovine serum albumin and lactoferrin had no effect on retinol uptake. However, serum retinol-binding protein (RBP), which shares structural and conformational similarities with BLG, also enhanced retinol uptake. BLG, BLG-retinol, and RBP-retinol all inhibited the uptake of retinol from BLG-[3H]retinol in a concentration-dependent manner. Uptake of retinol from BLG-retinol was saturable (apparent Km = 5.6 mumol/L, Vmax = 22.7 nmol.g-1.5 min 1), not affected by metabolic inhibitors, and partially temperature dependent (Q10 = 2.77). BLG also significantly (p less than 0.01) enhanced retinol uptake in the intestine of adult rats. These results demonstrate that BLG specifically enhances intestinal uptake of retinol and suggest the possibility of a receptor for BLG-like proteins at the brush border membrane of the enterocyte. PMID- 2929492 TI - Bioavailability of vitamin B-6 from plant foods. PMID- 2929491 TI - Dietary habits and incidence of noninsulin-dependent diabetes mellitus in a population study of women in Gothenburg, Sweden. AB - Dietary intake as initially estimated in a cross-sectional study has been related to the 12-y incidence of diabetes mellitus in a prospective study of 1462 women. In addition, all 50-y-old women (n = 352) were subjected to an intravenous glucose tolerance test. Because of the sampling procedure and a high participation rate the participants were representative of middle-aged women in the general population. No differences of statistical significance were observed concerning intake of energy and different nutrients. Neither did the number of meals nor the longest time between meals differ between women who developed diabetes and those who did not. Women with impaired glucose tolerance who developed diabetes did not differ from those who did not develop diabetes, concerning dietary intake. Body mass index was significantly higher in women who developed diabetes compared with other women. No specific dietary recommendations can be based on the results of this study. PMID- 2929493 TI - Vitamin E supplementation. PMID- 2929494 TI - Dendriform pulmonary ossification. Report of two cases with unique findings. AB - Dendriform pulmonary ossification (DPO) is a rare condition characterized by branching bony spicules found in association with pulmonary fibrosis. The authors report two cases, the first of which occurred in a patient with acute myeloblastic leukemia and was associated with the unique finding of leukemic involvement of marrow spaces in the metaplastic bone. The second case showed DPO in combination with asbestosis, a heretofore unreported association. PMID- 2929495 TI - Congenital bronchopulmonary foregut malformations. Intralobar and extralobar pulmonary sequestrations communicating with the foregut. AB - Two unusual variants of bronchopulmonary foregut malformations are presented. The first case was that of a 12-year-old male with a history of pectus excavatum in whom severe lobar emphysema developed secondary to an intralobar pulmonary sequestration that communicated with the esophagus. This case was unusual in that foregut communications and associated congenital anomalies are generally believed to be restricted to extralobar pulmonary sequestrations. The second case was that of a 27-year-old woman with an extralobar pulmonary sequestration that communicated with the esophagus. The sequestration was unusual in that it arose in the anterior mediastinum and received the bulk of its blood supply from the pulmonary artery. The occurrence of mixed forms of pulmonary sequestrations supports the hypothesis that extralobar and intralobar sequestrations and sequestrations with foregut communication are related thoracic disorders that are best considered bronchopulmonary foregut malformations. PMID- 2929496 TI - An in vitro bleeding time test. AB - A new conical plastic device and method, the Platelet-Stat test, has been developed to measure in vitro bleeding time. Ten milliliters of citrated blood, collected by venipuncture, was used. The in vitro bleeding time test was validated by several criteria. Eight volunteers tested had a mean bleeding time of less than 1 minute. Different anticoagulants were evaluated, and the test performed optimally with citrate. Within-run precision had a mean time of 39 +/- 6.7 seconds with a coefficient of variation of 17%. An aspirin study was done on eight volunteers. Preaspirin in vitro bleeding time was less than 1 minute, whereas postaspirin times were more than 7 minutes at 18-24 hours. This test is a reproducible method of performing the bleeding time with greater precision than the in vivo test. PMID- 2929497 TI - Lysed platelets shorten the activated coagulation time (ACT) of heparinized blood. AB - Aliquots of heparinized whole blood were incubated at 37 degrees C with preparations of lysed platelets or buffer. In the presence of lysed platelets, the ACT decreased to 127 seconds (+/- 41, n = 9) versus 248 seconds (+/- 43, n = 9) in the controls (P = 0.0002). The shortening of the ACT by lysed platelets followed a typical dose-response relationship. Fractionation of lysed platelet preparations revealed that the procoagulant membrane fraction, not the cytosol fraction containing PF4, was responsible for this effect of lysed platelets on the ACT. These findings demonstrate that the ACT can be artifactually low in the presence of heparin, indicating a potential problem in the use of the ACT for monitoring of heparin neutralization. PMID- 2929498 TI - Precision and reliability of paraprotein determinations by high-resolution agarose gel electrophoresis. AB - Agarose gel electrophoresis has recently replaced cellulose acetate electrophoresis as the preferred technique for monitoring paraprotein levels in patients with plasma cell dyscrasias. The authors studied the accuracy and precision of this method for paraprotein determination. Twenty-seven serum samples with paraprotein concentrations ranging from 5 to 73 g/L were aliquotted and assayed on 20 separate occasions, and the mean and standard deviation for the paraprotein concentration in each serum was established. Linear regression analysis showed that the standard deviation of paraprotein concentration (SD) increased as a function of paraprotein concentration (PC). For IgG paraproteins, the regression equation was SD = 0.041 (PC) + 1.06; R = 0.942; standard error = 0.32. For non-IgG paraproteins the equation was SD = 0.101 (PC) - 0.04; R = 0.851; standard error = 0.5. The accuracy of paraprotein determinations by the agarose gel electrophoretic technique was assessed by comparison with values obtained with the use of a previously validated enzyme-linked immunosorbent assay (ELISA) method for quantitation of IgG subclasses. Results obtained by the two methods were similar and highly correlated: (concentration by electrophoresis) = 0.921 (concentration by ELISA) + 0.46; R = 0.988; standard error = 0.34. The laser densitometric scanning procedure showed a loss of linearity above 60 g/L, indicating the need to dilute sera with very high paraprotein concentrations in order to obtain accurate results. A table is presented that should help pathologists who interpret such scans to determine whether small changes in paraprotein measurements occurring over time represent true changes in paraprotein concentration or merely reflect the analytic variability inherent in the technique. PMID- 2929500 TI - Sensitivity, specificity, and reproducibility of four measures of laboratory turnaround time. AB - The authors studied the performance of four measures of laboratory turnaround time: the mean, median, 90th percentile, and proportion of tests reported within a predetermined cut-off interval (proportion of acceptable tests [PAT]). Measures were examined with the use of turnaround time data from 11,070 stat partial thromboplastin times, 16,761 urine cultures, and 28,055 stat electrolyte panels performed by a single laboratory. For laboratories with long turnaround times, the most important quality of a turnaround time measure is high reproducibility, so that improvement in reporting speed can be distinguished from random variation resulting from sampling. The mean was found to be the most reproducible of the four measures, followed by the median. The mean achieved acceptable precision with sample sizes of 100-500 tests. For laboratories with normally rapid turnaround times, the most important quality of a measure is high sensitivity and specificity for detecting whether turnaround time has dropped below standards. The PAT was found to be the best measure of turnaround time in this setting but required sample sizes of at least 500 tests to achieve acceptable accuracy. Laboratory turnaround time may be measured for different reasons. The method of measurement should be chosen with an eye toward its intended application. PMID- 2929499 TI - Lucigenin-enhanced chemiluminescence in blood is increased in cancer. AB - The production of oxygen-derived cytotoxic metabolites by phagocytic cells is probably important in cancer cell killing. This production can be measured by chemiluminescence (CL). In the present report the authors have measured luminol and lucigenin-enhanced CL in whole blood from 63 untreated patients with cancer. In particular, the lucigenin-enhanced CL was increased in patients with cancer (P less than 0.001). No relation to origin or spread of the cancer was obvious. Monocyte number in peripheral blood was also significantly (P less than 0.01) increased as compared with age-matched controls. Further, the lucigenin-enhanced CL of purified monocytes, but not that of purified polymorphonuclear leukocyte(s) (PMNs), correlated significantly (P = 0.002) with the activity of whole blood. The authors conclude therefore that the highly increased lucigenin-enhanced CL observed in whole blood of a patient with cancer may reflect the enhanced production and activity of circulating monocytes that is a consequence of the body's defense reactions toward the developing cancer. PMID- 2929501 TI - Gastrointestinal neoplasia in young HIV antibody-positive patients. AB - In a period of less than one year, the authors observed three young patients in whom primary gastrointestinal carcinomas developed. Two of them had acquired immune deficiency syndrome and the other one was human immunodeficiency virus (HIV) antibody-positive drug abuser. This report is intended to alert the medical profession to gastrointestinal malignancy as a possible complication of HIV infection. PMID- 2929502 TI - Detection of the gene rearrangement in chronic myelogenous leukemia with biotinylated gene probes. AB - The breakpoint cluster region gene rearrangement associated with chronic myelogenous leukemia is becoming important in the diagnosis and management of the disease. At this time, the ability to demonstrate the gene rearrangement is limited to a few research laboratories. The problem results partially from unfamiliarity of medical laboratory personnel with DNA technology, but more because of the restricted use of radiolabeled phosphorus in hospital laboratories. With the introduction of biotinylated deoxynucleotides, nucleic acid hybridization procedures can now be performed without the use of radioisotopically labeled gene probes. This article describes the use of biotin labeled gene probes to detect the gene rearrangement of the breakpoint cluster region of chromosome 22 in chronic myelogenous leukemia. The techniques are reproducible, sensitive, and safe. With the procedures described in this article, the assay can become more available to medical laboratories interested in offering this diagnostic and decision-making tool. PMID- 2929503 TI - A two-institution study of transfusion practice in 78 consecutive adult elective open-heart procedures. AB - Blood salvage techniques and increasingly conservative physician transfusion practice in cardiac surgery have led to reports of homologous blood exposure in as few as 10% of patients having elective cardiac revascularization surgery (Ann Thorac Surg 1985;40:380). To identify current prevailing transfusion practice between centers, the authors prospectively audited 49 and 29 consecutive adult elective open-heart surgery cases (78 total) at two centers. Thirty-six of 49 patients (73%) received 245 homologous blood units (HBs) at institution 1 (m = 5.0). Fifteen of 29 (52%) received 84 HBs at institution 2 (m = 2.9, P less than 0.05). Sex, age, duration of surgery, intraoperative blood salvaged, preoperative hematocrit (Hct), nadir Hct, and nadir platelet counts, and the surgeon were all found to be determinants of transfusion practice at institution 1 but not at the other. The data indicate that (1) determinants of homologous blood exposure are not consistent between institutions and instead reflect "prevailing practice" rather than need; (2) a prospective multi-institution audit of prevailing transfusion practice in cardiac revascularization is needed to address this; (3) autologous blood pre-deposit is underused in open-heart surgery. PMID- 2929504 TI - The clinical significance of pure Bence Jones proteinuria at low concentration. AB - The clinical significance of Bence Jones (BJ) proteinuria at low concentration (less than 0.2 g/24 hours) was investigated in 33 unselected patients who had no intact monoclonal immunoglobulin in their serum. The great majority (79%) of the patients were recognized as having malignant lymphoproliferative diseases, such as chronic lymphocytic leukemia (46%), hairy cell leukemia (6%), and non Hodgkin's lymphoma (27%), whereas only two patients (6%) had multiple myeloma or systemic amyloidosis. Five patients (15%) had no evidence of definite malignant immunoproliferative disorders at the time of recognition of BJ proteinuria. Three of them, who were excreting steadily low amounts of BJ protein in their urine for 47, 61, and 73 months, respectively, without development of any B-lymphocytic malignancy, were classified as having a monoclonal gammopathy of undetermined significance. In the remaining two patients, BJ protein disappeared spontaneously 14 and 18 months, respectively, after its recognition. The study indicates that pure BJ proteinuria, even when occurring at low concentration, is most consistently associated with malignant proliferations of B-lymphocytic origin. However, the possibility should be considered that the clinical spectrum of the monoclonal gammopathy of the light chain type also includes benign and transient forms. PMID- 2929505 TI - Pediatric reference ranges for serum aldolase. AB - Most investigators have found that serum aldolase levels normally are higher in children than in adults. Although several earlier studies have included sufficient subjects to establish statistically reliable reference ranges, pediatric reference ranges have not been made available for the now widely used assay method of Pinto and associates (Clin Chem 1969;15:349-360.). The authors present age-related ranges determined by this method. PMID- 2929507 TI - Refractoriness to platelet transfusions. PMID- 2929506 TI - Non-Hodgkin's lymphoma of the central nervous system after treatment of Hodgkin's disease. AB - A case of a 34-year-old man with stage IIIB nodular sclerosis Hodgkin's disease complicated by the development of a central nervous system non-Hodgkin's lymphoma is described. The second tumor became symptomatic eight months after the initial diagnosis of Hodgkin's disease, but a tissue diagnosis was not made until autopsy two months later. The Hodgkin's disease was, at that time, in remission, and the autopsy revealed no persistent or recurrent Hodgkin's disease. Despite radiotherapy, the brain lymphoma had progressed to involve the spinal leptomeninges extensively, but there was no lymphoma outside the central nervous system (CNS) at autopsy. The significance of this unique case is discussed in light of the known risk for non-Hodgkin's lymphoma as a second malignancy after Hodgkin's disease and in view of recent information concerning CNS lymphoma. PMID- 2929508 TI - Blood culture bottles improve microbe isolation rate from joint fluids. PMID- 2929509 TI - Ulex Europaeus (UEA 1) PMID- 2929510 TI - Penicillium marneffei infection: a follow-up. PMID- 2929511 TI - Technologic anarchy? PMID- 2929512 TI - Nuclear magnetic resonance in the clinical laboratory. AB - Nuclear magnetic resonance (NMR) which now has widespread clinical use as an imaging technique, may also have significant application to diagnostic pathology. High-field proton NMR spectroscopy can perform rapid multicomponent analysis of serum, urine, cerebrospinal fluid, and even intact cells. This technique allows unusually detailed studies of certain metabolic derangements and toxic ingestions. Phosphorus NMR spectroscopy in vivo can measure ATP and other phosphometabolites, intracellular pH, and free Mg2+. It has been applied to diagnosing inborn errors of metabolism such as glycogen storage disease, monitoring growth and regression of tumors, and assessing tissue viability. The basics of NMR spectroscopy are reviewed in this article, along with a survey of applications in human pathology. PMID- 2929514 TI - Telepathology. Long-distance diagnosis. AB - Telepathology is defined as the practice of pathology at a distance, by visualizing an image on a video monitor rather than viewing a specimen directly through a microscope. Components of a telepathology system include the following: (1) a workstation equipped with a high-resolution video camera attached to a remote-controlled light microscope; (2) a pathologist workstation incorporating controls for manipulating the robotic microscope as well as a high-resolution video monitor; and (3) a telecommunications link. Progress has been made in designing and constructing telepathology workstations and fully motorized, computer-controlled light microscopes suitable for telepathology. In addition, components such as video signal digital encoders and decoders that produce remarkably stable, high-color fidelity, and high-resolution images have been incorporated into the workstations. Resolution requirements for the video microscopy component of telepathology have been formally examined in receiver operator characteristic (ROC) curve analyses. Test-of-concept demonstrations have been completed with the use of geostationary satellites as the broadband communication linkages for 750-line resolution video. Potential benefits of telepathology include providing a means of conveniently delivering pathology services in real-time to remote sites or underserviced areas, time-sharing of pathologists' services by multiple institutions, and increasing accessibility to specialty pathologists. PMID- 2929513 TI - Hypermedia in pathology--the Dartmouth Interactive Medical Record project. AB - Hypermedia and hypertext are the focus of intense interest in multiple disciplines in medicine, particularly pathology. This communication provides explanation of theories and applications that serve as motivation for the expansion of use of these technologies. The Dartmouth Interactive Medical Record (IMR) project is discussed. PMID- 2929515 TI - The diagnostic pattern in histopathology. AB - Defining in precise detail the diagnostic clues used by histopathologists to arrive at a diagnosis is a difficult process; however, better analytic understanding of this process is a prerequisite for the design of diagnostic expert systems. Such systems offer the potential for consistency and setting standards in the diagnostic evaluation of difficult situations. Diagnostic clues as offered by the image represent two-dimensional information. Their description is entered into the knowledge base of an aspect system, however, in the form of a description, which is one-dimensional. Preserving all of the two-dimensional dependence structure in this conversion is a fundamental problem. Use of the description to generate simulated imagery tests whether or not the two dimensional dependence structure of a given tissue architecture has been adequately represented in the analytic description. This analytic description would then be entered into the knowledge base of an expert system. PMID- 2929516 TI - Program and abstracts. Ambulatory Pediatric Association, twenty-ninth annual meeting. May 1-5, 1989, Washington, DC. PMID- 2929517 TI - Advances in neonatal care. PMID- 2929518 TI - Incomplete immunizations and the computer. PMID- 2929519 TI - Does methylprednisolone pulse therapy deteriorate the course of rapidly progressive IgA nephropathy? PMID- 2929520 TI - Parent-child minimal change nephrotic syndrome. PMID- 2929521 TI - Gonococcal conjunctivitis mimicking orbital cellulitis in a young adolescent. PMID- 2929522 TI - Polymicrobial bacteremia and child abuse. PMID- 2929523 TI - Risks of placing one-way valves in ventilator circuits. PMID- 2929525 TI - Connectedness. PMID- 2929524 TI - Neonatal intensive care. At what price? PMID- 2929526 TI - The effect of weight control on lipid changes in obese children. AB - The effects of weight change on serum lipid changes were assessed in a sample of 56 obese children randomly assigned to family-based behavioral obesity treatment vs controls given no treatment. Fasting serum lipid levels, height, weight, and fitness were measured at program entry and after 6 months of treatment. Children assigned to treatment showed significantly greater relative weight and weight changes than children in the control group, and the weight changes were significantly related to reductions in fasting serum triglyceride and total serum cholesterol levels and increases in high-density lipoprotein serum cholesterol. Results after 5 years of follow-up available for a small sample of treated children showed that a change in relative weight and fitness from 6 months to 5 years was also associated with changes in the high-density lipoprotein level. These results suggest that weight control in obese preadolescent children may be associated with improvement in lipoprotein profiles. PMID- 2929527 TI - Efficacy of a nonrestricted fat diet in patients with cystic fibrosis. AB - We sought to determine if an increased oral intake with a noninvasive nutrition program in patients with cystic fibrosis could influence growth, weight gain, and pulmonary function. Thirty-seven patients, aged 2 to 27 years, were instructed to consume a nonrestricted fat diet during an intervention period of 4 years. The results showed that patients increased the mean energy intake significantly to a level of more than 120% of the recommended daily allowance. The enhanced intake resulted in significant weight gain. Pulmonary function (forced expiratory flow 25%-75%) deteriorated during the 2-year preintervention period but stabilized during the 4-year intervention period. Both male and female patients were able to maintain their established height and weight scores during adolescence. The recommendation for a high-energy diet with no restrictions placed on the fat intake and the control of the steatorrhea by administration of an optimal enzyme dosage is supported by our data. Individualized nutritional counseling should be attempted before implementing invasive nutritional intervention programs. PMID- 2929528 TI - Adolescent health. Synopsis of a conference. AB - Adolescence can be subdivided into three interrelated components: biological, psychological, and sociocultural. Although the biological and psychological development of adolescents are largely generic processes, the social and cultural aspects strongly influence how these two processes are experienced. The plenary sessions of the First Annual American Medical Association Congress on Adolescent Health focused on the sociocultural factors that are currently influencing the adolescent experience. The lack of adult mentors in the job market, at home, and at school have left adolescents with minimal opportunities to interact with and learn from adults. Firm guidelines for responsible adult behavior have diminished, both through the subverting influence of television and the trend toward a value-neutral approach in education and preventive programs. Productive roles for adolescents have also dwindled; adolescents are primarily regarded as consumers. Physicians can help address these sociocultural issues by being a receptive and concerned adult to adolescents and to probe beyond simple presenting medical complaints to identify underlying development problems. PMID- 2929530 TI - Cardiorespiratory patterns during alarms in infants using apnea/bradycardia monitors. AB - Evaluating the significance of alarms at home in infants monitored for apnea/bradycardia depends on subjective parental observations. Retrospective analysis of 165 event recordings made during alarms in 90 monitored infants indicated that alarms were due to prolonged (greater than 15 s) apnea (6%), bradycardia (14%), shallow breathing (19%), mechanical malfunction (55%), or other causes (6%). Also, 68 infants had pneumograms. Of the 37 infants with an abnormal pneumogram, 14% had an abnormal event recording. Of the 31 infants with a normal pneumogram, 16% had an abnormal event recording. All monitors were discontinued without complication after a negative event recording. It may be concluded that (1) event recordings can document cardiorespiratory patterns during alarms, (2) the majority of alarms occurring at home are not significant, and (3) pneumograms do not appear to indicate which infants are at risk for a future significant alarm. PMID- 2929529 TI - Determinants of school performance in children with chronic asthma. AB - We have documented performance on standardized academic achievement tests for reading and mathematics in 99 children with moderately severe to severe chronic asthma. Academic performance and intelligence test scores indicated that, overall, the academic capabilities of the children with asthma were average to above average. A stepwise regression analysis was used to examine relationships between the dependent variables of reading and mathematics and the independent variables of socioeconomic status, school attendance, medical factors relating to asthma, age, and emotional and behavioral problems of the children. Factors that were associated significantly with low performance scores were low socioeconomic status, older age, history of continuous oral steroid use (prednisone or methyl prednisolone taken at least every other day for the year prior to evaluation), and presence of emotional and behavioral problems. School absenteeism, use of medical resources, oral steroid dosage, other medications used to treat asthma, and pulmonary functions were not associated with academic performance. Investigation of poor classroom performance of a child with chronic asthma should include investigation of the roles of socioeconomic status, oral steroid therapy, and emotional and behavioral problems. PMID- 2929531 TI - Use of adrenergic bronchodilators by pediatric allergists and pulmonologists. AB - Twenty-one pediatricians specializing in allergy, pulmonology, or both were questioned about their use of adrenergic bronchodilators for treating children of different ages at home, in the emergency department, and in the hospital. Most would use inhaled medications in all settings and for all ages. Few expressed strong preference for one drug over another, but only 2 would regularly use nebulized isoproterenol hydrochloride or isoetharine hydrochloride. Dosing frequency of inhaled medication at home was usually limited to every 4 hours, but in the emergency department or hospital, intervals between doses of 20 minutes or less were common. If this treatment failed, 9 physicians would use intravenous isoproterenol, but 4 strongly opposed its use. These results indicate that substantial variation exists in current expert practice, but that inhaled albuterol, metaproterenol, or terbutaline sulfate are most often preferred for treating asthma, bronchopulmonary dysplasia, and bronchiolitis in children of all ages, and that doses and dosing intervals are frequently altered to meet patient needs. PMID- 2929533 TI - Measured energy expenditure in pediatric intensive care patients. AB - Few data are available on energy requirements of mechanically ventilated, critically ill children. We measured the resting energy expenditure in 18 mechanically ventilated patients between ages 2 and 18 years, using indirect calorimetry. All patients had fractional inspired oxygen concentration less than 0.6, no spontaneous respirations, hemodynamic stability, and no fever or active infection, and were receiving 5% dextrose. All subjects were hypermetabolic, since the measured resting energy expenditure divided by the predicted basal energy expenditure from the Harris-Benedict equations was 1.48 +/- 0.09 (mean +/- SEM). The energy requirements calculated using "injury factors" and "activity factors" adapted for adults is 1.62 times basal energy expenditure. The injury factor for the pediatric multiple trauma patients should be 1.25 compared with 1.35 in adults. In these pediatric intensive care patients 33% +/- 8% of the energy is derived from carbohydrates, 53% +/- 8% from fat, and 14% +/- 2% from protein oxidation. In individual critically ill pediatric patients, energy requirements should be estimated by measuring their resting energy expenditure whenever possible and adding 5% for their activity. In the absence of the actual measurement of resting energy expenditure, the recommended energy requirement is 1.5 times basal energy expenditure. In this acute phase of injury, the daily nitrogen requirement is 250 mg per kilogram of body weight. PMID- 2929534 TI - Radiological case of the month. Intrathoracic stomach with volvulus. PMID- 2929532 TI - High school athletes and the use of ergogenic aid. AB - To determine high school athletes' attitudes toward and use of ergogenic aids, we surveyed 295 students presenting for preparticipation examinations. In general, young athletes believed that steroids and amphetamines were not efficacious in enhancing sports performance and that their use was potentially harmful. Subjects reported minimal use of steroids (1%) and amphetamines (2%), and only a minority would consider their use. As a group, however, male athletes were more likely to believe that steroids were effective (32% vs 13%) and to consider the future use of these agents (14% vs 0) compared with female athletes. The majority of high school athletes believed that supplemental protein or vitamins could improve performance and that their use caused little or no health risk. These data suggest that young athletes may require information regarding the limited benefits and potential risks associated with the use of ergogenic aids. PMID- 2929536 TI - The mirror's use in suicide. AB - Eleven suicides in which the victim took his or her life while looking into a mirror are presented. The psychoanalytic implications of this extreme form of narcissism are discussed. Investigators should have a high index of suspicion of suicide in cases where a dead body is positioned in front of or near a mirror. PMID- 2929535 TI - Suicide among nonwhites. The Metro Dade County experience, 1982-1986. AB - Suicide among nonwhites was studied using the case files of the office of the Medical Examiner of Metropolitan Dade County in Miami, Florida. A total of 116 cases, during the years 1982-1986, were analyzed as to the age, sex, cultural background, cause of death, blood alcohol content at autopsy, and reason for the suicide of the victim. By analyzing the ethnic/cultural backgrounds of the victims, it was noted that the overall rate of suicide among nonwhites in Dade County was 5 per 100,000 population per year. However, the rate varies within the overall group such that black-Hispanics, American Indians, and Haitians have suicide rates of 13.9, 11, and 3.1 per 100,000 population per year, respectively. Some of these rates are higher than the U.S. national nonwhite suicide rate of 7 per 100,000 population. Interestingly, while suicide rates are variable, the reasons listed for the suicide and the high frequency of young adult victims are similar to those for whites. A discussion ensues concerning this similarity and what future work in the field remains to be done. PMID- 2929538 TI - The "mini-packer" syndrome. Fatal ingestion of drug containers in Baltimore, Maryland. AB - We report seven fatalities resulting from the ingestion of illicit drugs packaged in condoms, rubber balloons, or plastic bags which were observed in the last 4 years at the Office of the Chief Medical Examiner, State of Maryland. All the victims, with the exception of one, were men ranging in age from 19 to 37 years. There was no racial predominance. No drug paraphernalia was found at any scene. In two cases, seizure-like activity was documented. One victim had recently returned from Nigeria; therefore, Lassa fever was initially suspected. Two of the victims were "body packer" contrabanders who had just arrived from Africa. They used body cavities to hide large amounts of heroin to avoid U.S. Customs. The other five cases were "mini-packers," small-time illicit drug dealers who had swallowed a single bag of cocaine to avoid police detection. The possible mechanism of leaking or rupture of the latex container is discussed. PMID- 2929537 TI - Accidental death due to falls at work. AB - The phenomenon of accidental death due to falls at work was studied: 15 cases that occurred during the years 1983-1987, in which a worker died from a job related fall, are presented in some detail. A discussion follows in which risk factors for these incidents are presented along with suggestions about how to investigate such cases. PMID- 2929539 TI - Seafaring bodies. AB - Cases involving two bodies that had drifted for at least 500 km on the high seas are described. PMID- 2929540 TI - Wischnewski revisited. The diagnostic value of gastric mucosal ulcers in hypothermic deaths. AB - Hypothermia is defined as a subnormal body temperature. In this article, hypothermia refers to the loss of core temperature from exposure. When death results from hypothermia, a series of gastric mucosal erosions known as "Wischnewski ulcers" (1) frequently occur. In examining case material of the Onondaga County Medical Examiner's Office, a characteristic pattern of these ulcerations was seen that was indicative of severe physiologic stress and/or hypothermia. While not pathognomonic of hypothermia, the incidence of the erosions in a specific pattern has been closely associated with deaths in which hypothermia played a significant role. In hypothermia, the erosions, usually shallow and approximately 0.1-0.5 cm in diameter, are set in lines with roughly equidistant spacing, thereby forming a pattern of rectangles with the corners marked by the ulcerations. PMID- 2929541 TI - Stomach contents and the time of death. Reexamination of a persistent question. AB - The inspection of the contents of the stomach must be part of every postmortem examination because it may provide qualitative information concerning the nature of the last meal and the presence of abnormal constituents. Using it as a guide to the time of death, however, is theoretically unsound and presents many practical difficulties, although it may have limited applicability in some exceptional instances. Generally, using stomach contents as a guide to time of death involves an unacceptable degree of imprecision and is thus liable to mislead the investigator and the court. PMID- 2929543 TI - Death due to hydrofluoric acid. AB - A case of death caused by an acid attack is presented. The victim, a young woman, was attacked by a person who threw acid onto her face. She reached the casualty department of a hospital where she died, a few hours later, from acute respiratory insufficiency due to the inhalation of acid vapors. The autopsy revealed severe chemical burns of her skin and lungs, with intense pulmonary hemorrhagic edema caused by the acid and its vapor. The subsequent chemical toxicological analysis and the police investigation confirmed that death was due to hydrofluoric acid. PMID- 2929542 TI - Postmortem metabolic indices of antemortem adrenergic stimulation. AB - Tissue lactate concentration has been reported to be a useful postmortem indicator of antemortem awareness of mortal danger. The purpose of this study was to determine further whether selected tissue metabolites could be used as postmortem markers of antemortem adrenergic stress. Sprague-Dawley albino rats were anesthetized with pentobarbital and then injected with 2.0 mg kg-1 i.p. epinephrine hydrochloride to induce experimentally a severe sympathetic response that may be associated with the awareness of mortal danger; 20 min after the injection of epinephrine, when the metabolic response was at its peak, the animals were killed by exsanguination. Samples of the following tissues were removed immediately prior to death (0 h) and 48 h postmortem: soleus, plantaris, kidney medulla, kidney cortex, liver, and heart. These samples were analyzed for glycogen, lactate, ATP, creatine phosphate, pH, and total protein concentration. Significant differences in lactate concentration were observed in all tissues except soleus at 0 h in the epinephrine-injected animals. Specific tissues also had significant reductions in glycogen, ATP, and creatine phosphate concentrations at 0 h. At 48 h postmortem, however, only the liver and soleus lactate concentrations were significantly different from the 48-h control samples. It is unlikely that these small differences found in some tissues at 48 h postmortem would be detected in an uncontrolled accident situation. We concluded from these findings that these selected tissue metabolites are not useful as long-term postmortem indicators of antemortem adrenergically induced hypermetabolism. PMID- 2929544 TI - Fatal intraoperative hemorrhage during spinal fusion surgery for osteogenesis imperfecta. AB - Osteogenesis imperfecta (OI) is an uncommon inherited systemic disorder of the connective tissues characterized primarily by varying degrees of bony fragility. Consequently, individuals affected by this condition frequently suffer severe skeletal injuries from otherwise innocuous traumatic events. This syndrome has other associated abnormalities, including hydrocephalus and brain stem compression on the basis of cranial developmental defects (platybasia), cardiac and vascular problems, respiratory disease from spinal deformities, vascular fragility, a bleeding disorder caused by an apparent platelet function abnormality, and anesthesia-related hyperpyrexia. A case is presented here of a young girl with advanced OI in whom intraoperative death occurred as a consequence of inadvertent rib fractures, with subsequent uncontrollable hemorrhage. OI may also potentially be mistaken for child abuse by an inexperienced examiner. PMID- 2929545 TI - "Spontaneous" coronary artery dissection. The challenge of detection, the enigma of cause. AB - Sudden death secondary to acute dissection of a coronary artery is a rare, but increasingly recognized, cause of sudden, unexpected death in apparently healthy persons. It has been reported more frequently in women and has been associated with sudden death during the puerperium. It has also been reported that these involved coronary vessels contain increased numbers of eosinophils and often show areas of cystic medial necrosis. In this article, we report a case of sudden death in a 47-year-old white woman due to dissection of the distal segment of her left anterior descending coronary artery. There was marked involvement of the coronary arterial walls with cystic degeneration of the media with accumulation of glycosaminoglycans as demonstrated by Alcian blue staining. There was no eosinophilic infiltrate within the arterial walls. This case is unusual in that this woman's mother and brother both have had aneurysms, which stresses the importance of not only searching carefully for these lesions, but also of obtaining family history in such cases. PMID- 2929546 TI - Dissecting aneurysm of the hepatic artery. AB - Aneurysms of the hepatic artery are rare and frequently diagnosed only at autopsy. First described by Wilson over 250 years ago, less than 400 cases have been reported in the literature (1,2). Dissection of these aneurysms is documented even less frequently, with only 11 cases reported in a review by Larson et al. (3). A case of sudden death from dissection and rupture of such an aneurysm was seen at the Westchester County Medical Examiner's Office, New York. PMID- 2929547 TI - Suppurative pericarditis due to Angelchik prosthesis. AB - Hiatus hernia is a common condition and while medical treatment is often sufficient, in some cases surgery may be necessary. Although there are a number of surgical treatments available, none has been totally successful. We report a case in which use of the Angelchik prosthesis proved fatal. PMID- 2929548 TI - Vaginal "fisting" as a cause of death. AB - We describe the death of a young girl that resulted from the insertion of a clenched hand and forearm into her vagina during heterosexual activity. (The male homosexual practice of rectal fist insertion has been described previously.) We believe this death to be the first reported case of a "fisting" death due to vaginal fist insertion during heterosexual activity. This death is reported to alert forensic pathologists, medicolegal death investigators, and coroners aware of the role of aberrant sexual activity and its potential to cause death. PMID- 2929549 TI - Drugs and homicide. PMID- 2929552 TI - What can be done to control incontinence associated with the irritable bowel syndrome? PMID- 2929551 TI - Earlobe creases. PMID- 2929550 TI - Senile cardiac amyloidosis and lethal arrhythmia. PMID- 2929553 TI - Peroral esophageal dilation over a guide wire: fluoroscopy, endoscopy, or "blind" passage. PMID- 2929554 TI - A marked guide wire facilitates esophageal dilatation. AB - Esophageal dilatation by endoscopists is a commonly performed procedure. The introduction of tapered polyvinyl dilators by Savary has made the procedure even more popular. In the United States, esophageal dilatation with guide wires has been traditionally performed with fluoroscopy. By using a marked guide wire and by adhering to specific safety guidelines, the passage of the guide wire can be precise, even without fluoroscopy, and radiographic definition is not always required. This study describes the new guide wire and the technique. PMID- 2929555 TI - Is long-term esophageal pH monitoring of clinical value? AB - Two hundred eighty-nine patients with various chest symptoms were studied by interview for the presence and type of symptoms, and by long-term esophageal pH monitoring for acid reflux. One hundred eighty of the patients also had upper gastrointestinal endoscopy. There was significant correlation between the results of all three methods. pH monitoring was more sensitive (92.9% vs. 81.0%) and specific (41.3% vs. 23.9%), and classified more patients correctly (55.6% vs. 37.2%), than an interview by an experienced gastroenterologist when esophageal erosions were regarded as "gold standard" for pathologic reflux. Of all patients, 31.5% had unclear symptoms and therefore could not be diagnosed by interview alone. Forty nine percent of these had pathologic reflux on pH monitoring. Among the patients, 72.3% who had symptoms typical of reflux disease also had a pathologic result at pH monitoring. It is concluded that most patients with unambiguous symptoms of esophageal reflux can correctly be diagnosed by interview, but that esophageal pH monitoring has a role in the management of patients with less characteristic chest symptoms. PMID- 2929556 TI - Clonidine prolongs human small intestine transit time: use of the lactulose breath hydrogen test. AB - Clonidine, an alpha 2-adrenergic agonist, has been shown to be useful in the treatment of some patients with chronic diarrhea. Previous animal and human studies have suggested that clonidine alters both small bowel fluid absorption and total gut motility. We measured the effect of clonidine 0.3 mg on oro-cecal transit time, using the lactulose-breath hydrogen test. Intestinal transit time in six normal healthy male volunteers after administration of clonidine was 148 +/- 20 min, and was 90 +/- 7 min with a placebo (p less than 0.05). The average prolongation in transit time was 69.5%. We conclude that clonidine may markedly alter human small intestine transit time which explains, at least in part, the mechanism for this agent's antidiarrheal effect. PMID- 2929557 TI - Intestinal gas production from bacterial fermentation of undigested carbohydrate in irritable bowel syndrome. AB - The relationship between abdominal pain and bowel gas from bacterial fermentation of undigested carbohydrate was investigated in nine patients with irritable bowel syndrome (IBS), six lactose malabsorbers, and 11 asymptomatic controls. All subjects took breath samples and marked analog scales for abdominal pain, bloating, and psychological stress hourly during all waking hours for 7 days. Breath samples were analyzed for hydrogen concentration within 3 days, and the concentration was corrected for storage time. Symptoms of pain and bloating were significantly more common in IBS patients than in lactose malabsorbers or normal controls, and pain was significantly correlated with bloating in IBS patients. Breath hydrogen concentration was similar in all three groups, and breath hydrogen was not correlated with pain ratings in IBS patients. Thus, abdominal pain may be related to bloating from gastrointestinal gas, but bacterial fermentation cannot be the cause of such gas. The most likely source is swallowed air. This study also demonstrates the feasibility of monitoring hydrogen production in the bowel in field studies by having subjects collect hourly breath samples. PMID- 2929558 TI - Evaluation of antibiotic-associated diarrhea with a latex agglutination test and cell culture cytotoxicity assay for Clostridium difficile. AB - Diagnosis of Clostridium difficile (C. difficile) by its antigen or toxin has improved treatment for patients who have antibiotic-associated diarrhea and opportunistic colonization of the colon with C. difficile. Unfortunately, results from the tissue culture cytotoxicity assay are not available for 48 h. We prospectively compared a latex agglutination test with the tissue culture cytotoxicity assay in 83 patients (15 with antibiotic-associated diarrhea, 23 with non-antibiotic-associated diarrhea, and 45 without diarrhea). In the antibiotic-associated diarrhea group, 43% of patients with pseudomembranes and 25% without pseudomembranes tested positive with both tests. In the non antibiotic groups 92% with diarrhea and 90% without diarrhea were negative with both tests. The number of discordant results illustrates the value of using two tests to identify C. difficile, since additional patients can be identified by using two tests. We found false positives were rare, and C. difficile toxin or antigen could not be detected in more than half the patients with pseudomembranes. The latex agglutination test for C. difficile is reliable, specific, and faster than the tissue culture cytotoxicity assay. The data suggest that other organisms may also be responsible for pseudomembranous colitis, and that negative tests do not obviate the need for visual evaluation of colonic mucosa in suspected cases of antibiotic-associated diarrhea. PMID- 2929559 TI - Carcinoma of the gallbladder and extrahepatic bile duct in autopsy cases of the aged, with special reference to its relationship to gallstones. AB - To demonstrate correlation between occurrence of carcinoma and that of gallstone of the gallbladder and biliary tract, we reviewed the protocols of gallbladder and extrahepatic biliary duct carcinoma and cholelithiasis of 4,482 cases (male 2,237, female 2,245, mean age 77.7 yr) autopsied at the Department of Pathology, Tokyo Metropolitan Geriatric Hospital, during the 27 yr from 1960 to 1986. Gallbladder carcinoma was found in 94 cases, or 2.1%. The incidence was higher in the female than in the male (male 24, female 70, p less than 0.01). Gallstone of the gallbladder was found in 957 cases or 21.4%. In the male, incidences of gallbladder carcinoma and stone increased with age until the lower half of the ninety, whereas in the female, no such tendency was found after the sixties. Incidence of gallbladder carcinoma was significantly higher in the cases with cholecystolithiasis than in those without stone (p less than 0.01). Furthermore, the incidence of gallbladder stones in the cases with relatively early carcinoma was significantly higher than that of those without carcinoma (p less than 0.01). Cholesterol stones were more common than bilirubinate in the carcinoma patients. These results suggest the importance of cholecystolithiasis, especially that of the cholesterol stones, as a background factor of gallbladder carcinoma. Extrahepatic bile duct carcinomas were present in 33 cases or 0.7% (male 19, female 14, no sex preference). The incidence was significantly higher in the cases with stones than in those without stones of the extrahepatic bile ducts (p less than 0.01). However, the fact that small stones were found in the upstream portions of obstruction of biliary tracts and no stone was found at operations in the 11 operated cases suggested that stones may be secondary to the cancerous growth. PMID- 2929561 TI - Splanchnic hemodynamics in idiopathic portal hypertension: comparison with chronic persistent hepatitis. AB - A comparative study of splanchnic hemodynamics was made in 12 patients with idiopathic portal hypertension and in eight patients with chronic persistent hepatitis, but without portal hypertension, who served as the control. Venous pressures were measured by portal and hepatic vein catheterizations, blood flow by the pulsed Doppler flowmeter, and organ volume by computed tomography. Splenic artery blood flow was 788 +/- 242 ml/min in idiopathic portal hypertension and about four times that in chronic persistent hepatitis (215 +/- 42 ml/min), whereas there was no difference in superior mesenteric artery blood flow between the former and the latter (408 +/- 142 vs. 389 +/- 32 ml/min). Spleen volume in idiopathic portal hypertension was six times that in chronic persistent hepatitis, and splenic artery blood flow showed a significant linear correlation with spleen volume in idiopathic portal hypertension (r = 0.71, p less than 0.02). The sum of splenic artery blood flow and superior mesenteric artery blood flow in idiopathic portal hypertension was 1195 +/- 294 ml/min, twice that in chronic persistent hepatitis (603 +/- 109 ml/min). Portal vascular resistance and intrahepatic portal vascular resistance were three times and four times those in chronic persistent hepatitis, respectively. These results indicate that both increased intrahepatic portal vascular resistance and increased splenic artery blood flow may play roles in the development of portal hypertension in idiopathic portal hypertension. PMID- 2929560 TI - Attitude of hospital personnel toward hepatitis B vaccination. AB - During a 1-yr period (November 1985-86), a free-of-charge vaccination program against hepatitis B was offered to 809 of the 1200 medical workers in a 650-bed general and regional hospital in Israel. Three hundred and eighteen (39.3%) accepted the offer and were vaccinated. The higher rates of acceptance were among cleaning personnel (96.3%) and student nurses (63.9%). The lower rates of acceptance were among physicians (46.5%) and nurses (24.9%). Different types of fear, as well as lack of knowledge, were the reasons responsible for 73.3% of all refusals. More specific and continuous health educational efforts among high-risk groups should be initiated for voluntary vaccination programs in Israel. PMID- 2929563 TI - Tuberculosis of the bile duct: a rare cause of biliary stricture. AB - The first case of biliary stricture due to tuberculous involvement of bile duct is presented. The diagnosis was established by choledochoscopic biopsy through a dilated percutaneous transhepatic biliary tract. Surgical bypass was impossible in this situation and endoprosthesis successfully relieved the biliary obstruction. PMID- 2929562 TI - Differences in portal hemodynamics in cirrhosis and idiopathic portal hypertension. AB - A comparative study of portal hemodynamics was made in 79 cirrhotics (24 cirrhotics with a large spleen greater than or equal to 500 cm3 in volume, 55 cirrhotics with a spleen less than 500 cm3 in volume), 22 patients with idiopathic portal hypertension, and 63 healthy adults who served as the control for portal and splenic venous flows. Portal and splenic venous flows were significantly increased in the group order of the cirrhosis without splenomegaly group, the cirrhosis with splenomegaly group, and idiopathic portal hypertension group. Intrahepatic shunt index was significantly greater in the cirrhosis with splenomegaly group than in the cirrhosis without splenomegaly group, and it was negligible in the idiopathic portal hypertension group. Portal vein pressure was significantly elevated in the cirrhosis with splenomegaly group than in the cirrhosis without splenomegaly and idiopathic portal hypertension groups. Postsinusoidal resistances were significantly greater in the two groups of cirrhosis than in the idiopathic portal hypertension group, whereas presinusoidal resistance was significantly greater in the idiopathic portal hypertension group than in the two groups with cirrhosis. It is concluded that these differences are inconsistent with the view that cirrhosis with splenomegaly comes from idiopathic portal hypertension. PMID- 2929564 TI - Primary biliary cirrhosis in a patient with multiple sclerosis. AB - A 47-yr-old patient with primary biliary cirrhosis and multiple sclerosis is reported. Although primary biliary cirrhosis has been associated with numerous other autoimmune disorders, it has not, to the authors' knowledge, previously been reported in association with multiple sclerosis. PMID- 2929565 TI - Nyquil-associated liver injury. AB - Acetaminophen, a commonly used medication, is present in many over-the-counter remedies. In recent years, its potential to cause severe liver injury has been increasingly appreciated. Chronic abusers of alcohol may be particularly susceptible to hepatotoxicity from acetaminophen. We report two cases of unintentional liver injury associated with ingestion of Nyquil, a liquid cold remedy containing acetaminophen and 25% alcohol. PMID- 2929567 TI - Liver cell adenoma: diagnosis and treatment of a rare hepatic neoplastic process. AB - Liver adenomatosis is a rare entity in which multiple liver cell adenomas (more than 10) occur in patients with no prior history of steroid use or glycogen storage disease. This report describes a case of liver adenomatosis, distinguishes liver adenomatosis from other benign liver lesions, and discusses the diagnosis and treatment of this disorder. PMID- 2929566 TI - Danazol-induced cholestasis. AB - A 39-yr-old female on high-dose Danazol presented with jaundice and pruritus. Danazol-induced cholestasis was suspected, and the drug was discontinued. A liver biopsy revealed panlobular cholestasis with portal and periportal inflammation. The cholestasis resolved completely in 8 wk. This is a rare case of Danazol induced cholestasis and should be considered in the differential diagnosis of drug-induced liver injury. PMID- 2929568 TI - Disseminated Salmonella arizona infection associated with rattlesnake meat ingestion. AB - Salmonella arizona is an uncommon enteric pathogen. We report a case of a woman with systemic lupus erythematosus, receiving prednisone therapy, who developed fatal disseminated S. arizona infection after ingesting raw dried rattlesnake meat as a form of treatment for her illness. S. arizona was isolated from stool, blood, peritoneal fluid, and cerebrospinal fluid. The importance of being aware of the Mexican-American folk remedy involving the ingestion of rattlesnake meat in the forms of dried snake, snake powder, or snake powder capsules, and the risk of acquiring S. arizona enteric infections is discussed. PMID- 2929570 TI - Ameboma presenting as acute urinary retention. AB - A patient with several weeks of diarrhea developed for the first time severe urinary frequency and urgency and was admitted with acute urinary retention. Imaging techniques showed a large mass compressing the posterior wall of the bladder adjacent to the rectosigmoid colon, leading to a bilateral dilatation of the ureters. Cystoscopy and biopsy of the affected part of the bladder showed no tumor but a nonspecific acute inflammation. After identification of trophozoites of Entamoeba histolytica in the stool and confirmation by colonoscopy, barium enema, and serology of acute amebic colitis, the patient was treated with metronidazole. Urinary symptoms immediately resolved with a complete disappearance of the mass and a later cure of the colitis. This is a first report of severe urinary symptomatology dominating the clinical picture in amebic colitis, due to compression of the urinary bladder by an ameboma. PMID- 2929569 TI - Segmental colitis associated with Aeromonas hydrophila. AB - We describe a 40-yr-old woman who presented with abdominal pain and diarrhea, and who was found to have segmental colitis involving the cecum and ascending colon. Aeromonas hydrophila was isolated from the stool, and her symptoms responded to appropriate antibiotic therapy. Follow-up colonoscopy confirmed complete endoscopic and histologic resolution of her colitis. This report further supports the belief that Aeromonas species are pathogens in healthy humans. This organism needs to be considered in the differential diagnosis of diffuse and segmental colitis. PMID- 2929571 TI - Mean and median of pH values, characterizing average intragastric acidity. PMID- 2929572 TI - Hemorrhagic acalculous cholecystitis in systemic lupus erythematosus. PMID- 2929573 TI - Acalculous gallbladder in common bile duct lithiasis patients. PMID- 2929574 TI - Granulomatous colitis 10 years after presentation with isolated Crohn's gastritis. PMID- 2929575 TI - Severe giardiasis in a child during cancer therapy. PMID- 2929576 TI - Peritonitis following colonoscopy in a cirrhotic with ascites. PMID- 2929577 TI - Listeria monocytogenes peritonitis: an additional case. PMID- 2929578 TI - Listeria monocytogenes spontaneous peritonitis. PMID- 2929579 TI - Detection of hypodiploidy using multi-parameter flow cytometric analysis: a prognostic indicator in multiple myeloma. AB - We analyzed 49 patients with multiple myeloma (MM) using propidium iodide (PI) staining and flow cytometry to assess DNA content of MM cells in bone marrow. In 12 patients the presence or absence of DNA content aneuploidy could not be determined by analysis of single-parameter DNA histograms alone. Using forward light scatter measurement, resolution of ploidy was readily obtained in all but three cases. Assuming the DNA content of the low light scatter population to be diploid, we were able to classify 7 cases as hypodiploid and 39 as hyperdiploid or diploid. Hyperdiploid or diploid patients survived a median of 24 months and hypodiploid patients only 2.5 months. We conclude that multiparameter analysis of DNA content and light scatter provides easier analysis for the presence or absence of aneuploidy. Patients with DNA content hypodiploidy have a short survival. PMID- 2929580 TI - Red cell ferritin and iron overload in heterozygous beta-thalassemia. AB - Red cell ferritin was evaluated in 101 individuals with heterozygous beta thalassemia to determine its clinical utility as an index for iron deficiency or overload in these subjects. The mean red cell ferritin for the total population was elevated threefold and showed a significant correlation with transferrin saturation, plasma ferritin, and HbA2 levels. Five of six subjects with reduced red cell ferritin had associated iron deficiency; a further five had iron deficiency and normal red cell ferritin. Normal red cell ferritin occurred in 51 subjects, and 44 had increased values. In the elevated red cell ferritin group, 21 individuals had associated normal plasma ferritin, and 23 had increased plasma ferritin. Only in the latter group was red cell ferritin significantly correlated with transferrin saturation and plasma ferritin. Ten individuals had a red cell ferritin greater than or equal to 150 attogram/cell, and liver biopsy performed in four showed grades II to IV iron overload. A clinical feature of subjects with both increased red cell and plasma ferritin levels was a high incidence of inappropriate iron administration. These findings suggest that red cell ferritin, particularly when combined with plasma ferritin, is a useful parameter for determining potential iron overload in individuals with heterozygous beta thalassemia. PMID- 2929581 TI - Platelet survival and turnover: important factors in predicting response to splenectomy in immune thrombocytopenic purpura. AB - Autologous indium-111 platelet sequestration and survival studies were performed on 59 immune thrombocytopenic purpura (ITP) patients, 21 of whom underwent splenectomy shortly thereafter. Sequestration patterns were primarily splenic in 46 patients, primarily hepatic in 6 patients, and both splenic and hepatic in 8 patients. The mean platelet survival ranged from 15 to 211 hr (normal, 180-220 hr), and mean platelet turnover (a measure of platelet production rate) varied from 99 platelets/microliters/hr to 7,585 platelets/microliters/hr (normal 1,200 1,600 platelets/microliters/hr). Among splenectomy patients, 13 had an excellent response, and 8 had a fair or poor response. Neither the pattern of platelet sequestration nor the quantity of platelet-associated IgG was useful in predicting response to splenectomy. There was, however, a striking correlation between platelet studies showing short survival/high turnover and subsequent excellent response to splenectomy. Conversely, patients with only moderately decreased survival and low turnover had an unpredictable response to splenectomy. This investigation demonstrates that ITP patients are a heterogeneous population and include a significant subset whose thrombocytopenia results primarily from decreased turnover. Platelet kinetic studies appear useful in predicting beneficial response to splenectomy. PMID- 2929582 TI - 8;21 translocation in myelodysplasia secondary to essential thrombocythemia. AB - A case is presented of a 73-year-old woman who received busulphan for essential thrombocythemia and subsequently developed a myelodysplastic syndrome (MDS), which transformed to acute nonlymphoblastic leukaemia within 1 month. Cytogenetic studies showed a 46,XX,t(8;21) (q22;q22) karyotype in all metaphases examined at diagnosis. The karyotypic abnormality is previously unreported in secondary myelodysplasia and may have specific clinical implications in this setting, such as early transformation to acute leukaemia and short survival. This finding contrasts with the generally favourable prognosis of the 8;21 translocation in patients with de novo acute nonlymphoblastic leukemia. A possible explanation for this difference may be the involvement of a committed progenitor in acute nonlymphoblastic leukaemia, while in myelodysplasia the more primitive multipotent stem cell may be affected. PMID- 2929583 TI - Thrombocytopenia associated with auranofin therapy: evidence for a gold-dependent immunologic mechanism. AB - Thrombocytopenia associated with gold therapy is thought to be due to an immune mediated mechanism. Relatively few patients have been studied so far, and precise details of the pathophysiology of this disease remain undetermined. We report a patient with gold-induced thrombocytopenia resulting from auranofin therapy. The patient's plasma contained platelet-reactive antibodies detectable only in the presence of gold salts. Antibody binding occurred at gold concentrations ranging from 0.01 to 10,000 ng/ml. The binding occurred independently of gold salt used, suggesting that substitution of a different gold preparation in this patient would result in a similar thrombocytopenia. These data support a drug-dependent immune mechanism for platelet destruction. PMID- 2929585 TI - Reversal of bone marrow fibrosis and subsequent development of polycythemia in patients with myeloproliferative disorders. AB - Bone marrow fibrosis is a characteristic finding in agnogenic myeloid metaplasia and in the spent phase of polycythemia vera. It is commonly believed that the reticulin deposition is irreversible. However, we report four patients who demonstrated clinical and laboratory evidence of transition from myelofibrosis to polycythemia. The transition was documented by improvement in the hemoglobin concentration and by determination of the Cr51 red blood cell mass, accompanied by a resolution of the fibrosis on serial bone marrow biopsies. Two of the patients had been treated with alkylating agents and splenectomy, one with myelosuppressive therapy without splenectomy, and one with splenectomy alone. These findings indicate that bone marrow fibrosis in the chronic myeloproliferative disorders is not always an irreversible phenomenon. Pathogenetic implications will be discussed. PMID- 2929584 TI - Hybrid acute leukemia in an HIV-antibody-positive patient. AB - Although the great majority of acute leukemias have been designated as being of lymphocytic or myelocytic origin, recent reports have described elements of both in some patients. We describe here the first case of hybrid acute leukemia in an HIV-antibody-positive patient as well as the first hybrid involving B-cell (Burkitt) acute lymphocytic leukemia and acute myelomonocytic leukemia proven by cytochemical, immunologic, and cytogenetic methods. This case illustrates the increasingly complex difficulties in the diagnosis and treatment of AIDS-related malignancies. PMID- 2929587 TI - Cyclosporin A in the treatment of severe aplastic anemia: description of a case complicated by the development of tubercular pericarditis during treatment. AB - We report on a 62 year-old woman who developed a severe aplastic anemia requiring frequent packed red cell and platelet transfusions. Since conventional pharmacological therapy was ineffective, treatment with Cyclosporin A was started, resulting in a significant increase of leukocyte, platelet, and red cell counts. However, 5 months after the beginning of Cyclosporin A treatment, despite a past medical history not significant for clinical tuberculosis, the patient developed tubercular pericarditis. This report underlines the need for a careful follow-up of Cyclosporin A-treated patients aimed at a prompt diagnosis of possible infectious complications. PMID- 2929586 TI - Long-term effect of splenectomy on transfusion requirements in thalassemia major. AB - Splenectomy reduces transfusion requirements in the first year after surgery in patients with thalassemia major and hypersplenism. To determine whether this response is maintained, we have studied transfusion requirements in 16 patients with thalassemia major for 2-17 years after splenectomy. Transfusion requirements remained stable (mean yearly change -0.1%) after the predictable fall in the first year after surgery. The mean change between the first postoperative year and the most recent year was -7 ml/kg. Transfusion requirements and the magnitude of change from year to year were unrelated to the time since splenectomy. These studies indicate that the effect of splenectomy on transfusion requirements is long-lasting and that large variations in annual transfusion requirements after splenectomy should prompt a search for accessory spleens or other causes of red cell destruction. PMID- 2929588 TI - Vasculitis in hairy cell leukemia: rapid response to interferon alpha. AB - A patient with hairy cell leukemia (HCL) and vasculitis was treated only with interferon alpha-2b. A good, rapid response was obtained without using corticosteroids or immunosuppressors. Interferon may prove to be useful for the systemic therapy of patients with vasculitis associated with HCL. PMID- 2929589 TI - Reversible agranulocytosis related to azidothymidine therapy. AB - Hematopoietic toxicity from Zidovudine (AZT) is fairly common, resulting in a requirement for red cell transfusions in up to 25% of patients. Reversible agranulocytosis occurred following approximately 1 week of AZT therapy in a man with AIDS. He recovered from the episode without incident. There was no evidence for underlying bone marrow dysfunction or an adverse drug reaction. Careful monitoring of AZT therapy continues to be of great importance. PMID- 2929590 TI - Ehrlichiosis: a cause of bone marrow hypoplasia in humans. PMID- 2929591 TI - Presidential address: the genetics of human behavior--lessons for two societies. PMID- 2929592 TI - Segregation analysis of translocations by the study of human sperm chromosome complements. PMID- 2929593 TI - Human chromosome 15 confers partial complementation of phenotypes to xeroderma pigmentosum group F cells. AB - Microcell-mediated transfer of a single human chromosome from repair-proficient human cells to genetic complementation group F cells from the hereditary disease xeroderma pigmentosum (XP) results in partial complementation of repair-defective phenotypes. The complementing chromosome was identified by cytogenetic and molecular analysis as human chromosome 15. Transfer of this chromosome to XP-F cells restores approximately 20% of the resistance of wild-type cells to killing by UV radiation or by the UV-mimetic chemical 4-nitroquinoline-1-oxide (4NQO), as well as partial repair synthesis of DNA measured as unscheduled DNA synthesis. Additionally, complemented XP-F cells have an enhanced capacity for reactivation of the plasmid-borne E. coli cat gene following its inactivation by UV radiation. Phenotypic complementation of XP cells by chromosome 15 is specific to genetic complementation group F; no effect on the UV sensitivity of XP-A, XP-C, or XP-D cells was detected. The observation that phenotypic complementation is partial is open to several interpretations and does not allow the definitive conclusion that the XP-F locus is carried on chromosome 15. PMID- 2929594 TI - Gene deletions in X-linked muscular dystrophy. AB - Of the approximately 170 families with X-linked muscular dystrophy of the Duchenne (DMD) and Becker (BMD) type in Finland, we have studied 90 unrelated patients for intragenic deletions by using the cDNA probes described by Koenig et al. Forty-five patients (50%) had molecular deletions of one or several of the 65 exon-containing HindIII fragments. In six deletion cases junction fragments of altered size were seen. Thirty-eight (84%) of the 45 deletions were detected using only two (1-2a and 8) of the six cDNA subclones. Using a wheelchair age of 12 years to distinguish between DMD and BMD, we found that the proportions of patients with deletions were similar. Deletions were equally common in familial and sporadic disease. BMD was more commonly caused by deletions in the 5' end of the gene than was DMD. In at least three instances deletions of similar type resulted in diseases of similar severity. Of 14 patients with mental retardation seven had deletions; six of these comprised exons contained in probe 8. We conclude that cDNA hybridization studies provide a powerful diagnostic tool in DMD and BMD and that they promise to produce better insights into molecular clinical correlations. PMID- 2929595 TI - An Asian-specific 9-bp deletion of mitochondrial DNA is frequently found in Polynesians. AB - One hundred fifty Polynesians from five different island groups (Samoans, Maoris, Niueans, Cook Islanders, and Tongans) were surveyed for the presence of an Asian specific length mutation of mitochondrial (mt) DNA by using enzymatic amplification with thermostable Taq DNA polymerase. Ninety-three percent of Polynesians exhibited this 9-bp deletion, including 100% of Samoans, Maoris, and Niueans. The same deletion was also found in 8% of Tolais from New Britain and in 14% of coastal New Guineans. A deletion frequency of 82% in Fijians confirmed their ethnic affinity to Polynesians. In contrast, the deletion was absent in 30 New Guinea highlanders and 31 Australian aborigines, the only exception being an aborigine who also had the Southeast Asian triplicated zeta-globin gene rearrangement in his nuclear DNA. These data support the theories claiming that an independent group of pre-Polynesian ancestors who colonized into the Pacific were ultimately derived from east Asia. PMID- 2929596 TI - Genetic homogeneity at the Friedreich ataxia locus on chromosome 9. AB - Classical Friedreich ataxia, a progressive, neurodegenerative disorder involving both the central and peripheral nervous systems, has been subclassified according to the observed clinical heterogeneity. The variations in the age at onset and in the spectrum and severity of symptoms have previously been interpreted as evidence of genetic heterogeneity. We have studied the linkage between the disorder and closely linked DNA markers in families of distinct ethnic origins, including the "typical" French-Canadians and the Acadian population of Louisiana. The disease in these two populations, both of continental French origin, has a very similar initial clinical picture. However, a marked difference in the rate of progression of the obligatory symptoms after 10 years of apparent disease is observed. A total of 553 individuals from 80 families with 202 affected members have been typed with the chromosome 9 marker MCT112, which we have previously shown to be closely linked to the disease locus. Evidence for linkage was observed in all families with the generation of a combined total lod score of 25.09 at a recombination fraction of theta = .00, providing strong evidence for genetic homogeneity at this locus for the classical form of this disease. PMID- 2929598 TI - The detection of linkage and heterogeneity in nuclear families for complex disorders: one versus two marker loci. AB - Using exact expected likelihoods, we have computed the average number of phase unknown nuclear families needed to detect linkage and heterogeneity. We have examined the case of both dominant and recessive inheritance with reduced penetrance and phenocopies. Most of our calculations have been carried out under the assumption that 50% of families are linked to a marker locus. We have varied both the number of offspring per family and the sampling scheme. We have also investigated the increased power when the disease locus is midway between two marker loci 10 cM apart. For recessive inheritance, both linkage and heterogeneity can be detected in clinically feasible sample sizes. For dominant inheritance, linkage can be detected but heterogeneity cannot be detected unless larger sibships (four offspring) are sampled or two linked markers are available. As expected, if penetrance is reduced, sampling families with all sibs affected is most efficient. Our results provide a basis for estimating the amount of resources needed to find genes for complex disorders under conditions of heterogeneity. PMID- 2929597 TI - Estimating the power of a proposed linkage study for a complex genetic trait. AB - Many genetic traits have complex modes of inheritance; they may exhibit incomplete or age-dependent penetrance or fail to show any clear Mendelian inheritance pattern. As primary linkage maps for the human genome near completion, it is becoming increasingly possible to map these traits. Prior to undertaking a linkage study, it is important to consider whether the pedigrees available for the proposed study are likely to provide sufficient information to demonstrate linkage, assuming a linked marker is tested. In the current paper, we describe a computer simulation method to estimate the power of a proposed study to detect linkage for a complex genetic trait, given a hypothesized genetic model for the trait. Our method simulates trait locus genotypes consistent with observed trait phenotypes, in such a way that the probability to detect linkage can be estimated by sample statistics of the maximum lod score distribution. The method uses terms available when calculating the likelihood of the trait phenotypes for the pedigree and is applicable to any trait determined by one or a few genetic loci; individual-specific environmental effects can also be dealt with. Our method provides an objective answer to the question, Will these pedigrees provide sufficient information to map this complex genetic trait? PMID- 2929599 TI - Factor IXPortland: a nonsense mutation (CGA to TGA) resulting in hemophilia B. AB - Male siblings with severe hemophilia b were studied for the molecular defect responsible for their disorder. To define the precise DNA alteration, a 362-bp fragment in the first part of exon VIII of the factor IX gene was amplified and sequenced. A single-base-pair substitution of C----T at the nucleotide sequence 30875 was found which resulted in a nonsense mutation (TGA) and terminated the protein synthesis of factor IX at amino acid residue 252. The single-base change occurred as a classic CG dinucleotide alteration to TG (or CA), a common mechanism for point mutations in mammals. PMID- 2929601 TI - Nontraditional pedagogy for implementing human genetics education. PMID- 2929600 TI - A male carrier for Duchenne muscular dystrophy. PMID- 2929602 TI - Report of the First Information and Education Committee Human Genetics Teaching Forum, held at the 1988 ASHG annual meeting at New Orleans on October 12, 1988. PMID- 2929603 TI - Genetics education in the People's Republic of China. AB - The National Education Commission of the People's Republic of China directs all educational course content from kindergarten to graduate level in all disciplines. The study of genetics is thus controlled by the members of the commission, so there is little variation of course offerings from one institution to another. Formal genetics education begins in lower middle school and is expanded somewhat in upper middle school (high school). Middle school marks the end of the formal education for most Chinese students, although many graduates learn the practical aspects of genetics while working in agricultural plant and animal breeding. Students who continue the study of genetics in universities find that course work is concentrated and research is encouraged, although facilities and supplies are limited. On graduation from a university, most students are sent to factories to use their expertise for increasing food production, while a very small percentage of students continue on to graduate school and eventual research and university teaching. The area of human genetics is handled exclusively in medical schools. PMID- 2929604 TI - Encephalopathy: an uncommon manifestation of workplace arsenic poisoning? AB - This report describes two cases of chronic encephalopathy associated with occupational exposure to arsenic fumes from hot pressurized impregnation of wood. Both cases displayed symptoms of cognitive impairment with onset 14-18 months after start of occupational exposure to arsenic fumes. Laboratory confirmation was provided by elevated urine arsenic levels. One patient was hospitalized for apparent psychiatric reasons. Neuropsychologic testing of one case showed typical and relatively mild impairments of new learning, recent memory, and concentration in addition to the psychological symptoms. Symptoms in both cases disappeared following cessation of exposure and return of urine arsenic excretion to normal levels. In future studies of workers exposed to arsenic, documentation of mild impairment of cognitive function should be sought using neurobehavioral test batteries. PMID- 2929605 TI - Parental occupational lead exposure and lead concentration of newborn cord blood. AB - The purpose of this study was to determine the influence of parental occupational lead exposure on the lead levels of newborn cord blood in the Taipei area. From September 1984 to June 1985, 5,000 pregnant women voluntarily participated in the study at the Taipei Municipal Maternal and Child Hospital. Each woman was interviewed regarding her and her husband's occupational exposures; 2,948 successfully delivered healthy newborns, and cord blood samples were obtained using Terumo Venoject, and 242 samples were analyzed by graphite furnace atomic absorption spectrometry using an Instrumentation Laboratory 251 instrument. Nine cord blood samples were from newborns with both parents exposed, 26 samples had maternal exposure only, 105 samples had paternal exposure only, and 102 were nonexposed. The results showed that the average lead level of cord blood with both parents exposed was 8.9 +/- 2.9 micrograms%, maternal exposure 9.0 +/- 3.8 micrograms%, paternal exposure 8.3 +/- 3.4 micrograms%, and 6.9 +/- 3.2 micrograms% in the nonexposed group. There were significant differences between the nonexposed and the maternal exposure groups, and also between the nonexposed and paternal exposure groups. All 26 maternal exposures were from lead soldering operations. Multivariate analysis revealed that, after control of father's exposure status, newborn cord blood lead level increased 0.27 micrograms% for each hour the mother spent on lead soldering during a normal working day, thus suggesting that soldering during pregnancy may be hazardous to newborns. Paternal contribution to the cord blood lead levels seemed to be through either working at home with the pregnant mother also at home or bringing work clothes home for laundering. PMID- 2929606 TI - Cumulative arsenic exposure and lung cancer in smelter workers: a dose-response study. AB - The cause-specific mortality was followed through 1981 in a cohort of 3,916 male Swedish smelter workers employed for at least 3 months from 1928 through 1967. Arsenic levels in the air of all workplaces within the smelter were estimated for three different time periods. Using this exposure matrix and detailed information of the work history, cumulative arsenic exposure could be computed for each worker. Standardized mortality ratios (SMRs) were calculated for several dose categories using age-specific mortality rates from the county where the smelter was situated. A positive dose-response relationship was found between cumulative arsenic exposure and lung cancer mortality with an overall SMR of 372 (304-450, 95% confidence interval). The lung cancer mortality was related to the estimated average intensity of exposure to arsenic but not to the duration. No positive dose-response relationship was found between arsenic and ischemic heart disease or cerebrovascular disease. There was also no evident dose-response relationship between estimated exposure to sulfur dioxide and lung cancer. PMID- 2929607 TI - Potroom asthma: New Zealand experience and follow-up. AB - Occupational asthma related to work in potlines in an aluminum smelter has been diagnosed on clinical criteria in 57 workers. About half were regular tobacco smokers but atopy was uncommon. There was a wide range in the time for which each had been employed prior to development of symptoms, but the average was about 20 months. Thirty-four showed nonspecific bronchial hyperreactivity to methacholine. At annual reviews over a period of 5 years following transfer to other work at the smelter, the majority improved in symptoms in 1-2 years and bronchial hyperreactivity returned to normal. However, over the subsequent 3 years, deterioration, not limited to tobacco smokers or atopic subjects, has occurred in some subjects. PMID- 2929608 TI - Deaths and tumors among workers grinding stainless steel. AB - This study examined a cohort of 1,164 males who, during the period 1927-1981, had been employed for 3 months or more in an industry that produced objects from stainless steel. These workers were exposed to the dust of grinding materials, grinding agents, and stainless steel. From 1975 to 1980, measurements of the total dust in the workroom air have shown levels of about one mg/m3 (consisting of chromium at about 0.1 mg/m3 and nickel at about 0.05 mg/m3) during grinding and several mg/m3 (chromium at about 0.01 mg/m3 and nickel at about 0.005 mg/m3) during polishing. Before 1950, the concentrations were probably considerably higher. Compared to a local reference population, a decrease in mortality (63 observed deaths, standardized mortality (SMR) = 0.79, 95% confidence limits CL = 0.61, 1.01) took place during the 1951-1983 observation period among 318 subjects who had been employed for at least five years, allowing a latency period of at least 20 years. Mortality from cancer of the colon/rectum increased (observed deaths = 6, SMR = 2.47, CL = 0.97, 5.58). The mortality from nonmalignant pulmonary disease did not increase (SMR = 0.29, CL = 0.01, 1.81). During the observation period (1958-1983), there was no significant overall excess of tumors (observed cases = 33, standardized morbidity [SMR] = 1.09, CL = 0.76, 1.54). However, tumor morbidity of the colon/rectum (observed 11, SMR = 2.83, CL = 1.47, 5.19) significantly increased. There were no cases of respiratory cancer (expected 4.7, CL = 0, 0.21). Thus, the results indicate an increased risk of intestinal cancer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2929609 TI - Improvement in the occupational health program in a Finnish construction company by means of systematic workplace investigation of job load and hazard analysis. AB - The aim of the present study was to improve an occupational health program by means of systematic workplace investigations. The 8-month study was done at three building sites of one construction firm. The method for workplace investigations was a simple job hazard analysis of chemical hazards, physical hazards, physical work load, mental stress, and risk of injury, each factor being rated on a three point scale. Information was gathered by observations, interviews, and a worker questionnaire. Occupational health and safety personnel and worker representatives dealt with problems cooperatively. Together they assessed occupational loads and hazards, whereafter the occupational health and safety personnel devised an occupational health care program and proposed preventive measures. The workplace investigation method proved to function well. It improved the occupational health care program, produced an overall analysis of occupational hazards, and dramatically increased the number and quality of proposed preventive measures. The new method was evaluated to be clearly superior to previous practices and was implemented at moderate cost. The study showed that attention to issues of environmental and occupational health can effectively prevent health impairment even in difficult setting such as construction work. More research is needed for effective utilization of information accumulated by systematic workplace investigations. PMID- 2929610 TI - Chronic respiratory disorders related to farming and exposure to grain dust in a rural adult community. AB - In a survey of chronic respiratory symptoms and airflow obstruction of a rural population aged 20-65 years, the effects of both farming and, in particular, the exposure to grain dust on the respiratory health of the people was examined. Of the 1,892 subjects (82% of the eligible population) studied, 924 were males and 968 females, with half living in the town. Three groups were identified: current, former, and never farmers. Almost all current farmers were exposed to grain for, on average, 2 months a year. There was no difference in atopic status between the groups. While there was a strong association between most symptoms and smoking, there was no association between symptoms and exposure to grain and farming category once age and smoking had been taken into account. Results of this study suggest that farmers do not have chronic respiratory symptoms or impairment of lung function because of their exposure to grain dust. Lung function of former farmers might have been affected by farming, and this may reflect more involvement with livestock in the past. PMID- 2929612 TI - Prospective study of respiratory effects of formaldehyde among healthy and asthmatic medical students. AB - We conducted a prospective evaluation of pulmonary function and respiratory symptoms among 103 medical students exposed to formaldehyde over a 7-month period to determine the incidence of bronchoconstriction and respiratory symptoms in response to exposure. Time-weighted average formaldehyde exposures were generally less than 1 part per million (ppm) and peak exposures were less than 5 ppm. Acute symptoms of eye and upper respiratory irritation were significantly associated with exposure. There was no pattern of bronchoconstriction in response to exposure after either 2 weeks or 7 months. Twelve subjects had a history of asthma; they were no more likely to have symptoms of respiratory irritation or changes in pulmonary function than those without such a history. These findings are consistent with previous case reports that indicate exposure to formaldehyde vapor at levels that are commonly encountered in occupational and residential settings do not commonly cause significant bronchoconstriction, even among subjects with preexisting asthma. PMID- 2929611 TI - Concordance of occupational and environmental exposure information elicited from patients with Alzheimer's disease and surrogate respondents. AB - Identification of risk factors for Alzheimer's disease through the use of well designed case-control studies has been described as a research priority. Increasing recognition of the neurotoxic potential of many industrial chemicals such as organic solvents raises the question of the occupational and environmental contribution to the etiology of this high-priority health problem. The intention of this study was to develop and evaluate a methodology that could be used in a large scale case-control study of the occupational and environmental risk factors for dementia or a population-based surveillance system for neurotoxic disorders. The specific objectives of this study were to investigate: 1) the reliability of exposure-eliciting, interviewer-administered questionnaires given to patients with Alzheimer's disease (SDAT); 2) the reliability of exposure eliciting interviewer-administered questionnaires given to the family of patients with SDAT and the agreement with the responses of the patient or surrogate respondents; 3) the reliability and agreement of responses of age- and sex matched control patients and their families selected from geriatric care institutions and the community, with respect to the same exposure-eliciting and interviewer-administered questionnaire; and 4) the reliability of agent-based exposure ascertainment by a single, trained rater. The results of the study demonstrate that occupational and environmental histories from which exposure information can be derived is most reliably elicited from job descriptions of cases and control subjects rather than job titles alone or detailed probes for potential neurotoxic exposures. This will necessitate the use of standardized interviewer-administered instruments to derive this information in case-control studies of Alzheimer's disease or population-based surveillance systems for occupational and environmental neurotoxicity. PMID- 2929613 TI - Incompletely studied hazards of waste incineration. PMID- 2929614 TI - Mortality among workers at a municipal waste incinerator. AB - Mortality was investigated among 176 male workers employed for at least 1 year between 1920 and 1985 at a municipal waste incinerator. Expected numbers of deaths from 1951 to 1985 were calculated from national and local death rates, standardized for age and calendar year. There was an excess of deaths from lung cancer and, after long follow-up, for ischemic heart disease. Analysis of duration of exposure supported that the excess of ischemic heart disease was caused by occupational factors; the lung cancer cases were too few to permit conclusions in this respect. Exposure to combustion products and polycyclic aromatic compounds were common, but other occupational exposures may also have contributed to the risk excesses. Smoking habits were investigated and did not differ from the average for Swedish men in cities and towns. Some work operations are very dusty and should be performed only with appropriate protection devices. PMID- 2929615 TI - Medical surveillance of hazardous waste workers: ability of laboratory tests to discriminate exposure. AB - The assessment and cleanup of hazardous waste sites has become a growth industry. Unlike traditional factory employment, chemical exposures on wastes sites are likely to involve uncharacterized mixtures. Medical surveillance of hazardous waste workers has become a major preventive strategy. To evaluate the effectiveness of the traditional laboratory tests employed in most surveillance programs, we compared test results in two groups of hazardous waste workers (409 males, 68 females) with responsibilities for the assessment and management of waste sites. We stratified employees into a group with a high potential for exposure ("exposed") and a group with a low potential for exposure ("unexposed"). Fifty-five clinical chemistry, hematologic, and urinalysis variables were contrasted using an analysis of variance. The only consistently significant difference was a low mean corpuscular volume in the "exposed" group. The lack of other significant findings suggests that either the true exposure status of individuals was not reflected in our classification or that the traditional tests were inappropriate or insensitive. We conclude that it is essential to evaluate surveillance results carefully and to develop protocols that are appropriate to the actual exposures encountered in hazardous waste work. PMID- 2929616 TI - Injuries on the fireground: risk factors for traumatic injuries among professional fire fighters. AB - This case-control study within a metropolitan fire department evaluated the effect of self-contained breathing apparatus (SCBA) and other risk factors on three types of injury at the scene of a fire (smoke inhalation, burns, and falls). Data on 75 injured fire fighters and 144 controls came from telephone interviews and department records. The two sets of uninjured fire-fighter controls were matched to cases on incident (n = 72) or on job position and fire type and size (n = 72). Smoke inhalation cases were not significantly different from controls in SCBA use, cigarette smoking, previous fires in the shift, or injury history. Jobs with high risk of burns included nozzle operator, engine officer, and forcible-entry person in first-due companies (OR = 20.1). Other risk factors for burns were: basement origin of fire (OR = 10.2); prior fire-fighting training outside the present department (same fire: OR = 11.2; similar fire: OR = 3.9); and on-duty injury in the prior 12 months (same fire: OR = 4.3; similar fire: OR = 3.5). When other risk factors were considered, consistent SCBA use was associated with falls (same fire: OR = 11.8; similar fire: OR = 4.3) but not with burns. Risk of falls also was elevated among members of truck companies (OR = 17.7) and fire fighters without children (same fire: OR = 8.4; similar fire: OR = 7.4). On-duty injury in the past 12 months was associated with falls when one compared cases with similar-fire controls (OR = 5.5), but not with controls attending the same fire. Neither age nor experience was related to injury in this population. PMID- 2929617 TI - Critical review of cancer epidemiology in petroleum industry employees, with a quantitative meta-analysis by cancer site. AB - A critical review of close to 100 published and unpublished but otherwise available epidemiologic reports of petroleum industry employees from the United States, United Kingdom, Canada, Europe, Australia, and Japan was conducted. Analyses by duration of employment and latency are discussed, and summary standardized mortality ratios (SMRs) or meta-SMRs are developed for selected cancer sites. Findings indicate that the industry experienced a significantly lower cancer mortality than the general population for all cancer sites combined, digestive system, stomach, and lung. For the industry as a whole, SMRs similar to the general population were observed for skin, brain, pancreatic, prostatic, and kidney cancers. However, some data indicate that certain small groups within the industry might have elevated prostatic and kidney cancer risk. This review supports the conclusion that some refinery employees, particularly those employed before the 1940s, may have been at increased risk of leukemia. There is some indication that cancer of other lymphatic tissue may also be elevated. Unresolved issues affecting these conclusions are discussed, and specific directions for future research are offered. PMID- 2929618 TI - Respiratory symptoms among Swedish swine producers. AB - Two hundred nine male farmers engaged in swine production, born in 1913 or later, and alive in 1985 received mailed questionnaires on respiratory symptoms, medical history, and exposure to contaminated air in swine confinement buildings. The response rate was 76%. The prevalence of three or more symptoms of bronchitis was higher than that in welders who had completed the same questionnaire--Mantel Haenszel odds ratio 5.26 (1.9-14.8) for smoking subjects. The number of reported symptoms was strongly influenced by smoking habits (p less than .01) and by exposure (p less than .01), and by a positive interaction between these (p less than .01, two-way analysis of covariance). Air in swine confinement buildings is contaminated with bacterial endotoxins and organic dust, and it is concluded that it may pose a risk for airways diseases such as chronic bronchitis. PMID- 2929619 TI - Comparison of smoking-related risk factors among black and white males. AB - The lung cancer risk factors of smoking prevalence, amount smoked, and age started to smoke were compared for blacks and whites, using the 1970 and 1979/80 National Health Interview Survey (NHIS) survey data. For both survey years, proportionally more blacks were never smokers and fewer were ever smokers (although more were current and fewer former smokers). The average adult black smoker smoked approximately 65% of the number of cigarettes smoked by the average white adult. Blacks started smoking later than whites for almost all occupational categories. Thus, it could be argued that whites had higher smoking-associated risk factors than did blacks. At the same time, a much greater proportion of blacks than whites were in the types of occupation where they would have been exposed to occupational hazards. The sharp rise in and the larger incidence of lung cancer among blacks compared to whites may not be due to differences in black and white smoking, but more likely are a reflection of occupational differences. PMID- 2929620 TI - Mortality comparisons of chemical workers hired before, during, and after World War II (1941-1945). AB - Cause-specific mortality was evaluated by period of hire for 37,682 male chemical workers in order to test the hypothesis that employees hired during World War II (1941-1945) were at increased risk for selected causes of death. One recent study of refinery workers reported that those hired during the war years had experienced greater mortality from external causes (accidents, homicides, and suicides), alcoholism, and cancers of several sites relative to employees hired before or after the war. In the present study, employees were divided into three period-of-hire subcohorts: prior to 1941, 1941-1945 (World War II), and 1946 and after. Comparison of observed mortality among these subcohorts through 1982 was made with expected levels based on age- and calendar year-specific U.S. white male rats. Neither hourly nor salaried employees hired during the war showed evidence of higher mortality from homicide, suicide, alcoholism, or any of the selected cancer types suggested from the refinery study. Hourly, but not salaried, war years new hires experienced excessive mortality from only those accidents involving motor vehicles. Possible reasons for the discrepant findings between this and the earlier study of refinery workers are discussed, with methodological differences being dismissed. PMID- 2929621 TI - Standard setting, science, and politics. PMID- 2929623 TI - Isolated systolic hypertension: a long-neglected cause of cardiovascular complications. PMID- 2929622 TI - The risk of miscarriage and birth defects among women who use visual display terminals during pregnancy. PMID- 2929624 TI - High-density lipoprotein cholesterol is reduced in patients with sarcoidosis. AB - PURPOSE: Sarcoidosis is a disease in which the proliferation of monocyte macrophage-derived cells is observed. In other diseases characterized by expansion of the monocyte-macrophage system, such as Gaucher's disease and myeloid metaplasia, abnormalities of lipoprotein metabolism have been demonstrated. To determine whether similar abnormalities in lipoprotein cholesterol concentrations could be identified in patients with sarcoidosis, we studied total cholesterol, low-density lipoprotein (LDL) cholesterol, and high density lipoprotein (HDL) cholesterol as well as triglyceride levels in 52 patients with biopsy-proven sarcoidosis. PATIENTS AND METHODS: Patients had no other medical disorders and were not being treated with corticosteroids or antimalarial agents. Blood samples were collected by venipuncture after an overnight fast. Plasma total cholesterol and triglyceride levels were measured using enzymatic techniques. Lipoprotein cholesterol was quantified by lipoprotein fractionation. HDL cholesterol was measured as cholesterol remaining in the supernatant after precipitation of LDL and very-low-density lipoprotein from whole plasma by the heparin-maganese chloride method. Computation was used to determine the level of LDL cholesterol. RESULTS: We found significantly reduced levels of total cholesterol (183.9 +/- 27.6 versus 194.3 +/- 16.5 mg/dl, mean +/- SD, p = 0.021) and HDL cholesterol (41.2 +/- 13.0 versus 51.9 +/- 6.1 mg/dl, p = 0.0001) in sarcoid patients versus an age-, sex-, and race-matched reference group. Differences were not observed in triglyceride or LDL cholesterol levels (p greater than 0.05). CONCLUSION: These findings are similar to those observed in the myeloproliferative diseases, Gaucher's disease, and rheumatoid arthritis and suggest a functional role for monocytes-macrophages in the regulation of serum lipoprotein cholesterol levels. PMID- 2929625 TI - Bloodstream infections in the elderly. AB - PURPOSE: Bacteremia in the elderly is associated with a different clinical course and a higher mortality rate when compared with that in younger age groups. In order to examine these issues in the aged, we reviewed the clinical course and factors involved in the outcome of 100 episodes of bloodstream infections in patients over 65 years of age. PATIENTS AND METHODS: The hospital records of all patients over 65 years of age at The Mount Sinai Hospital with a positive blood culture result during the period October 1984 to October 1986 were reviewed. Place of residence before hospital admission, site of acquisition of infection, source of bloodstream infection, and microorganism were analyzed. Antimicrobial therapy was defined as appropriate if initial therapy included one agent to which the isolate was sensitive, or inappropriate if the isolate was resistant. The following factors affecting survival were analyzed: age, sex, underlying diseases, clinical parameters on admission, white blood cell count, mental status, source of infection, microorganism isolated, antibiotic toxicity, and appropriate versus inappropriate antibiotic therapy. RESULTS: Most patients were female (63 percent), were febrile (90 percent), had an altered mental status (52 percent), and had a neutrophilic response (61 percent). Eighty-three percent of patients were admitted from the community (home), 14 percent were from long-term care facilities, and 3 percent were transferred from other hospitals. Fifty percent of infections were nosocomial, and 44 percent were community (home and nursing home)-acquired. Gram-negative organisms accounted for 60 percent of isolates, with Escherichia coli (22 percent) and Klebsiella species (11 percent) predominating; 30 percent were gram-positive organisms, with Staphylococcus aureus (13 percent) and Streptococcus faecalis (10 percent) the most common. The overall survival was 60 percent; the survival rate was 65.8 percent for community acquired (home) bacteremia, 75 percent for nursing home-acquired bacteremia, and 52.8 percent for hospital-acquired bacteremia. Survival for gram-negative isolates was 65 percent, versus 51.7 percent for gram-positive isolates. Survival was greatest in patients whose source of bacteremia was either the genitourinary tract (70 percent) or an intravascular device (78 percent) and poorest in patients with lower respiratory tract source (42 percent); all three patients with endocarditis died. Increased survival was observed in patients treated with appropriate antimicrobial agents regardless of age, source of infection, or bloodstream isolates.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2929626 TI - Long-term follow-up of aggressively treated idiopathic rapidly progressive glomerulonephritis. AB - PURPOSE: We wanted to examine the long-term effects of aggressively treating idiopathic rapidly progressive glomerulonephritis (RPGN), with a particular focus on clinically characterizing the patient population, assessing the short- and long-term effects of therapy on renal function, and determining complications of the therapy. PATIENTS AND METHODS: Twenty-three consecutive patients with RPGN were treated and followed from one to 11 years. On renal biopsy, 13 had immune complexes, eight had no immune complexes, and two had antiglomerular basement membrane deposits. All had greater than 25 percent crescents and 19 of 23 had greater than 50 percent crescents. Every patient responded on a short-term basis to either large-dose pulse methylprednisolone or plasma exchange, with reduction of the mean plasma creatinine level from 6.5 +/- 2.0 mg/dl to 2.9 +/- 1.0 mg/dl (p less than 0.001). Each patient received oral prednisone and all but one received cyclophosphamide. RESULTS: Three died of non-renal causes. Fifty percent of the remaining 20 patients maintained stable renal function for at least two years. Four of nine patients followed-up for longer than two years had a relapse, but all responded again to therapy. No characteristic clinical symptoms predicting relapse were found, although nearly all had hematuria and proteinuria. Complications of therapy were frequent and may have contributed to death in two patients. CONCLUSION: Thus, long remissions are seen in most patients with RPGN treated aggressively. PMID- 2929627 TI - Aortic insufficiency and mitral regurgitation in patients with systemic lupus erythematosus and the antiphospholipid syndrome. AB - PURPOSE, PATIENTS, AND METHODS: Heart disease has not been well characterized in patients with systemic lupus erythematosus (SLE) and the antiphospholipid syndrome. During a prospective study of cerebrovascular disease in autoimmune disease and SLE, 11 lupus patients were identified with an antiphospholipid syndrome characterized by significant cardiac valvular disease in addition to cerebral infarction, deep vein thromboses, and thrombocytopenia. Patients were reviewed for criteria for systemic lupus and underwent echocardiographic studies and measurements of anticardiolipin antibodies, VDRL, and the lupus anticoagulant. RESULTS: Eight of the 11 patients had aortic insufficiency, two of whom had associated mitral regurgitation. Three patients had mitral regurgitation alone. Microscopic analysis of a surgically excised aortic valve indicated typical Libman-Sacks verrucous endocarditis. Infective endocarditis was ruled out in all patients. CONCLUSION: This report expands previous descriptions of antiphospholipid syndromes by describing a subset of lupus patients with significant aortic and mitral valvulitis in addition to circulating antiphospholipid antibodies, thrombocytopenia, and recurrent thromboses. PMID- 2929628 TI - Normal left ventricular performance documented by Doppler echocardiography in patients with long-standing hypocalcemia. AB - INTRODUCTION: Several reports suggest significantly reduced left ventricular performance in subjects with chronic hypocalcemia. We prospectively investigated eight patients, aged 13 to 31 years, with long-standing hypocalcemia due to idiopathic hypoparathyroidism or pseudohypoparathyroidism by echocardiography. PATIENTS AND METHODS: Six subjects had symptomatic hypocalcemia manifested as recurrent tetany (four), seizures (four), mental retardation (three), behavior disorder (one), and skeletal abnormalities (four); three subjects were untreated when studied. None had cardiovascular symptoms. Each patient underwent clinical, biochemical, and cardiac studies, including Doppler, two-dimensional, and M-mode echocardiography, on the same day. RESULTS: In serum, both total and ionized calcium concentrations were reduced and averaged 7.2 mg/dl (range: 5.3 to 8.5 mg/dl; normal: 9.0 to 10.3 mg/dl) and 3.6 mg/dl (range: 3.0 to 3.9 mg/dl; normal: 4.5 to 5.3 mg/dl), respectively. Electrocardiograms revealed prolonged QTc intervals in six patients. Also noted were prominent U waves (five), T-wave abnormalities (four), and right-axis deviation (one). Resting echocardiography, however, demonstrated normal left ventricular function in all subjects. All M mode measurements were normal. Two-dimensional-derived left ventricular end diastolic and end-systolic volumes were 87.1 +/- 20.1 ml and 30.2 +/- 9.7 ml (mean +/- SD), respectively. Left ventricular ejection fraction was 65 percent (61.2 to 74.7 percent). Doppler-derived cardiac output and cardiac index averaged 5.1 liters/minute (2.9 to 6.7 liters/minute) and 3.0 liters/minute/m2 (1.7 to 4.3 liters/minute/m2), respectively. CONCLUSION: Our prospective study of eight subjects with functional hypoparathyroidism demonstrated that, despite electrocardiographic abnormalities, long-standing hypocalcemia was not associated with left ventricular dysfunction. PMID- 2929630 TI - The nonvalue of retrospective peer comparison feedback in containing hospital antibiotic costs. AB - Antibiotics have accounted for an increasing percentage of hospital pharmacy charges. Recently, an inexpensive method, automated peer comparison feedback, has been developed to influence physician use of resources. The documented success of several implementations of this strategy led to a one-year experiment to influence hospital antibiotic utilization. Each month, attending physicians in the top 50 percentiles for expenditure were notified of their status in relation to their peers. Expenditures by feedback and control groups were compared to determine whether feedback would result in reduced expenditures by individuals, or whether there would be a generalized reduction in expenditure by the entire group (Hawthorne effect). Over the year, no significant reduction in expenditure was noted. However, some important utilization patterns were identified. Although more surgical patients received antibiotics than did nonsurgical patients, surgical antibiotic costs were less. Surgical therapy was typically of shorter duration and involved the use of less expensive antibiotics. Multiple-antibiotic prescribing was less frequent on surgical services. Thirty percent of attending physicians were responsible for 80 percent of all antibiotic costs; 60 percent of those in this top group were members of the medical cohort. IN CONCLUSION: (1) As implemented in the current study, automated peer comparison feedback was not an effective method for reducing antibiotic utilization; (2) Differences in prescribing patterns between services may dictate the best strategies for improving antibiotic utilization; (3) More attention should be directed toward the relatively small "reference group" of physicians responsible for most hospital antibiotic prescribing. PMID- 2929629 TI - Transient hypertension after two phenylpropanolamine diet aids and the effects of caffeine: a placebo-controlled follow-up study. AB - PURPOSE AND PATIENTS AND METHODS: Reports of severe adverse reactions following the ingestion of single (75 mg) or double doses of the sympathomimetic drug phenylpropanolamine (PPA), with and without caffeine, prompted us to undertake a study of the effects of five drug preparations (75 mg PPA, 150 mg PPA, 75 mg PPA plus 400 mg caffeine, 400 mg caffeine, and placebo) in 16 resting, normotensive subjects. The study was of a double-blind, randomized, crossover design. Each subject consented to take the five drug preparations on different study days, which were separated by at least 48 hours. RESULTS: Compared with blood pressure (BP) values obtained after placebo ingestion, significant BP increases occurred over several hours following 150 mg PPA and after 75 mg PPA plus 400 mg caffeine. Significant BP increases after ingestion of 75 mg PPA and after 400 mg caffeine were less frequent. The mean peak BP following 150 mg PPA was 173 +/- 9/103 +/- 4 mm Hg, compared with 148 +/- 4/97 +/- 3 mm Hg after the other three active preparations; after placebo, peak BP reached 137 +/- 8/85 +/- 5 mm Hg. CONCLUSION: These results indicate that 150 mg PPA (the amount in two diet aids) substantially elevates BP. Our findings may explain some of the recent case reports of nontraumatic intracranial hemorrhage in young, healthy persons ingesting PPA at recommended or minimally greater dosages. We suggest physicians inform patients who are likely consumers of PPA (i.e., those with allergies, those with eating disorders, overweight persons, women during the postpartum period) and patients at risk for stroke (i.e., the elderly and hypertensive patients) of the risks of taking more than the recommended amounts of PPA and of combining caffeine with PPA. PMID- 2929631 TI - Rhabdomyolysis with pneumococcal pneumonia: a report of two cases. PMID- 2929632 TI - Azidothymidine-induced hyperpigmentation mimicking primary adrenal insufficiency. PMID- 2929633 TI - Pancreatitis and typhoid fever. PMID- 2929634 TI - Acute pericarditis due to group C Streptococcus: report of a medically treated case. PMID- 2929636 TI - Nicotinic acid-associated myopathy: a report of three cases. PMID- 2929635 TI - Treatment of cutaneous granulocytic sarcoma in a patient with myelodysplasia. AB - In this report, we have presented our experience with a patient with a rare cutaneous granulocytic sarcoma. In addition to hematoxylin and eosin, myeloperoxidase stain and specific stains for lysozyme and esterase were helpful in confirming the histologic diagnosis of granulocytic sarcoma. Despite multiple attempts to control this patient's tumor by conservative surgery, radiation therapy, and chemotherapy, we eventually had to resort to limb amputation. This procedure restored a meaningful quality of life to this patient for one and a half years prior to the development of acute leukemia. Treatment with corticosteroids at the time of surgery may have prevented a local recurrence of granulocytic sarcoma despite positive tissue margins. Our experience underscores the importance of directing treatment toward the granulocytic sarcoma whereas the myelodysplasia concurrently present may not require therapy for several years. PMID- 2929637 TI - Agoraphobia and hyperthyroidism. PMID- 2929638 TI - Report of an unusual case of postoperative adrenal hemorrhage in a young woman. PMID- 2929639 TI - Occult pulmonary embolism presenting with thrombocytopenia and elevated fibrin split products. PMID- 2929640 TI - Endocarditis due to Pasteurella multocida with glomerulonephritis. PMID- 2929641 TI - Low-dose cytosine arabinoside as remission induction therapy in refractory adult acute lymphocytic leukemia. PMID- 2929643 TI - Short-term recovery of visual field loss in acromegaly during treatment with a long-acting somatostatin analogue. PMID- 2929642 TI - Prolonged hypernatremia associated with azotemia and hyponatriuria. PMID- 2929644 TI - Systemic lupus erythematosus presenting with portal venous thrombosis. PMID- 2929645 TI - Dural metastasis from laryngeal malignant carcinoid. PMID- 2929647 TI - Cryptosporidium in the elderly: a cause of life-threatening diarrhea. PMID- 2929649 TI - Valvulitis in systemic lupus erythematosus. PMID- 2929648 TI - Heme therapy. PMID- 2929646 TI - Nail discoloration and human immunodeficiency virus infection. PMID- 2929650 TI - Myalgias in human immunodeficiency virus-infected patients. PMID- 2929651 TI - Bicarbonate in the treatment of severe hyperkalemia. PMID- 2929652 TI - Complications of long-acting somatostatin analogue therapy. PMID- 2929653 TI - Induction of theophylline toxicity and inhibition of clearance rates by ranitidine. PMID- 2929654 TI - Orofaciodigital syndrome type IV: report of a patient. AB - We describe a further patient with the orofaciodigital syndrome type IV. The clinical characteristics include lobulated tongue, pseudo-cleft of lip, pre- and postaxial polydactyly of hands and feet, severe talipes equinovarus, mesomelic limb shortness associated with tibial hypoplasia, and severe bilateral deafness. Five similar cases including the present patient are now on record. Autosomal recessive inheritance is likely. PMID- 2929655 TI - Mutation rate estimates are not compatible with autosomal dominant inheritance of the dysplastic nevus "syndrome". AB - Dysplastic nevi represent precursor lesions harboring an increased risk of evolving into melanoma. Their association with familial melanoma is usually considered a monogenic syndrome with autosomal dominant transmission. To test this concept we estimated the mutation rates. When derived directly from the sporadic occurrence of the trait, the mutation rate is exceedingly high (0.9% 2.5%), whereas, as estimated with the aid of Haldane's formula it would be 0.007% to 0.02%. Accordingly, newly arising mutation would outnumber eliminated mutations by 100:1. Even if only 80% of all old mutations are passed onto the next generation, this ratio of 100:1 would rapidly change. After only a few generations, 10% of the world population should be affected with the dysplastic nevus "syndrome". The apparent lack of a genetic equilibrium between newly arising and eliminated mutations is not compatible with autosomal dominant inheritance of the dysplastic nevus "syndrome." PMID- 2929656 TI - Atrial septal defect, ventricular septal defect, and coarctation of the aorta in sibs: an autosomal recessive disorder? AB - We report on two sisters with secundum atrial septal defect, perimembranous ventricular septal defect, and coarctation of the aorta. Identical anatomical malformations were verified by echocardiography and at operation. No other affected relatives were identified. We suggest that this is a specific, possibly recessively inherited type of complex cardiac malformation. PMID- 2929657 TI - A new syndrome with distinct facial and auricular malformations and dominant inheritance. AB - We report on a mother and son with high forehead; elongated and flattened face; arched, sparse eyebrows; short palpebral fissures; telecanthus; long nose and hypoplastic nostrils; long philtrum; microstomia; high, narrow palate; nasal speech; chin dimples; and a highly unusual bilateral auricular malformation. Intelligence and hearing are normal, and there is no "whistling" face or deviation of fingers. Although resembling in some ways the Freeman-Sheldon syndrome, this phenotype most likely represents a new malformation syndrome, either autosomal dominant or X-linked dominant. PMID- 2929658 TI - Congenital pulmonary atresia with intact ventricular septum, tricuspid insufficiency, and patent ductus arteriosus in two sibs. AB - Pulmonary atresia comprises only 1% of all congenital heart defects. Counseling the parents on recurrence risks is difficult. We present a rare case of pulmonary atresia in two sibs, along with a review of the literature. PMID- 2929659 TI - Syndrome of imperforate oropharynx with costovertebral and auricular anomalies. AB - This is the second report of a syndromic form of imperforate oropharynx associated with costovertebral and auricular anomalies. PMID- 2929660 TI - Interstitial long-arm deletion of chromosome 7 and ectrodactyly. AB - An interstitial deletion of 7q21 was found in a boy with mental retardation, microcephaly, convergent strabismus, micrognathia, genital anomalies, and other findings, including ectrodactyly. PMID- 2929661 TI - Further delineation of a syndrome of cerebellar vermis hypo/aplasia, oligophrenia, congenital ataxia, coloboma, and hepatic fibrosis. AB - Three children are described from two sibships. They share infantile ataxia with hypo/aplastic vermis, hepatic fibrocirrhosis, slender-shaped skeleton, peculiar face, and moderate mental retardation. One of them had a kidney biopsy that showed mild interstitial fibrosis and amyloid deposit, but had no functional impairment. Another suffered moderate proximal tubular acidosis. Two children had unilateral or bilateral choroidal coloboma. This pattern of defects is consistent with a syndrome previously reported in two other sibships. The acronym COACH (Cerebellar vermis hypo/aplasia, Oligophrenia, congenital Ataxia, Coloboma, Hepatic fibrocirrhosis) is suggested. PMID- 2929662 TI - First International Symposium on the Marfan syndrome. July 8-10, 1988, Baltimore, Maryland. Abstracts. PMID- 2929663 TI - 3-M syndrome. PMID- 2929664 TI - Genital overgrowth in the EMG syndrome. PMID- 2929665 TI - No correlation between hyperthermia during pregnancy and Hirschsprung disease in the offspring. PMID- 2929666 TI - Antley-Bixler syndrome from a prognostic perspective. PMID- 2929667 TI - Potential for the prenatal diagnosis of hyperornithinemia, hyperammonemia, and homocitrullinuria syndrome. PMID- 2929669 TI - Congenital scalp defects with distal limb anomalies (Adams-Oliver syndrome McKusick 10030): further suggestion of autosomal recessive inheritance. PMID- 2929668 TI - Facial anomalies in congenital cutis laxa with retarded growth and skeletal dysplasia. PMID- 2929670 TI - Colposcopy and computer graphics: a new method? AB - A new method is herein described that uses the most recent computer science techniques to obtain digitalized colposcopic images that may be useful not only as documents, but also as research tools. Because computer graphics is a recent and ever-growing discipline, our method, too, might undergo considerable improvements: some possible improvements are hypothesized in the text. The most striking features of this method are the excellent quality of images, their easy reproducibility, and the reasonable cost. PMID- 2929671 TI - Outcome of very-low-birth-weight infants: does antepartum versus neonatal referral have a better impact on mortality, morbidity, or long-term outcome? AB - To evaluate the effect of aggressive intrapartum and early neonatal resuscitation on perinatal mortality, neonatal morbidity, and long-term outcome, we evaluated two groups of low-birth-weight infants who received different intrapartum and early neonatal care. One group of infants was delivered at a university-based regional perinatal center offering both high-risk obstetric and tertiary neonatal care. The second population consisted of infants from five community hospitals with level I nurseries. These two groups were selected because they differed in the ability to provide intrapartum and early neonatal care and because a total base population could be evaluated. During the 4-year study period, 174 infants with birth weights of 500 to 1499 gm were delivered at the university center and 297 infants were delivered at the community hospitals. At the university center, there was a significant reduction in fetal deaths, a delay in the time of neonatal deaths, and a reduction in hyaline membrane disease. Neonatal mortality rates at the university center were not reduced, and the incidence of sequelae was not affected. These data suggest that for the smallest infant, intrapartum and immediate neonatal care at a tertiary center may decrease fetal mortality and neonatal morbidity rates. Neonatal mortality and long-term outcome, however, may be less affected. PMID- 2929672 TI - Outcome of very-low-birth-weight infants: are populations of neonates inherently different after antenatal versus neonatal referral? AB - Postnatal transfer of high-risk infants to a neonatal intensive care unit has been an accepted medical practice for more than two decades. More recently, antepartum maternal referral for the smallest infants has been recommended to reduce infant mortality, morbidity, and long-term handicaps. The limited data available to compare in utero and postnatal transfer suggest that maternal risk factors may also influence antenatal referral. We evaluated antepartum maternal and postnatal infant referrals from five metropolitan Denver hospitals with level I facilities. Mothers who were referred to the tertiary perinatal center before delivery were more likely to have one or more high-risk conditions. The presence of a maternal risk factor (preeclampsia, antepartum bleeding, prolonged rupture of the membranes, or chorioamnionitis) was significantly more common in the maternal transfer group (p less than 0.002). Neonatal weight was higher for the maternal referrals compared with neonatal referrals. Neonatal survival was independently improved by transport of mother or infant, increasing birth weight, and higher Apgar scores. We suggest that maternal risk factors were an important determinant in the choice of antenatal referral to our perinatal center for both the community and regional hospitals during this study period. Studies that compare outcome of infants after maternal and infant transfer must control for potentially inherent differences between the antenatally and postnatally transferred infants. PMID- 2929673 TI - Direct demonstration of iron in a term placenta in a case of beta-thalassemia major. AB - Successful term pregnancy in homozygous beta-thalassemia is rare. A pregnant patient with thalassemia usually is found to have chronic anemia concurrent with tissue and circulatory iron overload. We have demonstrated and localized iron deposits in a term placenta of a patient with homozygous beta-thalassemia with the use of routine histochemical staining. PMID- 2929674 TI - Mechanism and clinical significance of elevated CA 125 levels in the sera of pregnant women. AB - To clarify the mechanism of CA 125 elevation in maternal sera, serum levels of CA 125 and CA 19-9 were measured in 122 apparently healthy pregnant women (fifth to fortieth week of gestation) and 50 postpartum women (26 term deliveries and 24 second-trimester induced abortions). Serum levels of CA 125 showed an initial increase by the tenth week and then decreased to less than 35 U/ml, remaining below this level until delivery. However, within 1 hour after term delivery or second-trimester induced abortion, the CA 125 levels showed a second increase and decreased rapidly thereafter. In contrast, serum levels of CA 19-9 did not change significantly during these periods. Combined with our previous finding that the decidua contains abundant CA 125 but little CA 19-9, these results indicate that the elevated CA 125 levels in maternal sera originate from the decidual cells affected by chorionic invasion or the placental separation. PMID- 2929675 TI - Rupture and dehiscence of cesarean section scar during pregnancy and delivery. AB - A prospective study was undertaken to evaluate the risk of uterine rupture or dehiscence after cesarean section. During the 10 years of the study, 24,644 patients were delivered of infants. Of these women, 2036 (8.3%) had previously undergone cesarean section. A trial of labor was allowed in 1008 of these patients, and 92.2% were delivered vaginally. The incidence of uterine rupture in this trial of labor group was 0.6%, compared with 0.4% in the total group. Cesarean section scar rupture caused no serious complications in either the mothers or the offspring in the trial of labor group. Uterine rupture in this group was not associated with use of oxytocin or epidural analgesia. Patients with lower-segment scar rupture had no history of puerperal pyrexia. The incidence of uterine dehiscence was 4%. In summary, the risk of uterine rupture in patients who have previously undergone cesarean section but are allowed a trial of labor is low and not associated with serious complications. Vaginal delivery is therefore considered the safest route of delivery in these patients. PMID- 2929676 TI - Gonococcal chorioamnionitis associated with sepsis: a case report. AB - We present a case of gonococcal chorioamnionitis in a patient with intact membranes, which has not been previously reported. Evidence suggests that the spread of bacteria was transplacental. PMID- 2929677 TI - Feasibility of placental biopsy in the second trimester for fetal diagnosis. AB - Second-trimester prenatal diagnosis by placental biopsy was possible in 200 of 220 patients (90.9%) to whom it was offered to expedite cytogenetic analysis. Cytogenetic analysis was successful in 190 cases (95%) when the material obtained was greater than 2 mg. We found five chromosome abnormalities; 47,XX, +21 (two cases); 47,XY, +18 (one case); and 45,XX,t (D;G) (two cases). There was one abortion 4 weeks after the placental biopsy (0.4%). If further experience confirms the accuracy, safety, and reliability of this method beyond the first trimester, it can be offered to mothers to expedite the cytogenetic, biochemical, and deoxyribonucleic acid analysis. PMID- 2929678 TI - Serum and bile lipid levels in a postmenopausal woman after percutaneous and oral natural estrogens. AB - 17 beta-Estradiol was administered for 4 weeks percutaneously (5 mg/day) and, after a 6-week period to allow the drug to wash out, orally (2 mg/day) to a postmenopausal woman in whom a Kerr tube had been placed because of an iatrogenic lesion of the common bile duct. After both methods of administration, there was an increase in the biliary cholesterol concentration, but after oral administration, bile flow also increased and cholesterol crystals appeared in the bile. The percutaneous method of estradiol administration in postmenopausal women seems to be less dangerous for the biliary tract. PMID- 2929679 TI - Purification and characterization of a uterine phospholipase inhibitor that loses activity after labor onset in women. AB - Gravidin, a protein that inhibits release of arachidonic acid from human decidual cells, was purified from amniotic fluid. The protein has a molecular weight of 58 to 60 kilodaltons, an isoelectric point of 8.4, and physical characteristics that are indistinguishable from those of inhibitor II previously described. Activity was determined in a dispersed decidual cell system that released arachidonic acid in response to either histamine or calcium ionophore and in a cell-free assay of phospholipase A2. Protein purified from incubates of chorion obtained after the onset of labor was significantly less active than that from chorion obtained before the onset of labor. PMID- 2929680 TI - Temporal relationships of neuropathologic conditions caused by perinatal asphyxia. AB - The neuropathologic conditions in 120 perinatal deaths attributed to fetal or newborn asphyxia were examined. Central nervous system necrosis was present in 16 of these deaths. The approximate time of asphyxial insult was established by determining the duration of the process, based on the findings of neuronal necrosis, macrophage response, or an astrocyte response, in conjunction with clinical data. The time of the asphyxial insult for the 16 perinatal deaths was as follows: antepartum fetal asphyxia, two cases; antepartum-intrapartum fetal asphyxia, five cases; intrapartum fetal asphyxia, four cases; and neonatal asphyxia, five cases. These observations indicate that an asphyxial insult may occur in the antepartum period, in the prodromal period of preterm labor, in the intrapartum period, and in the neonatal period. Five to ten percent of the asphyxial insults in each reproductive time period were initially sublethal, allowing necrosis of the brain of the fetus or newborn to develop. PMID- 2929681 TI - Terbutaline (intravenous bolus) for the treatment of acute intrapartum fetal distress. AB - beta 2-Sympathomimetics have been used in acute intrapartum fetal distress to abolish uterine contractions and thus enable the fetal metabolism to recover before delivery. Because some serious complications were reported when a terbutaline intravenous bolus (0.25 mg) was used as a tocolytic, we assessed its safety and efficacy when used in patients not affected by cardiovascular disease, tachycardia greater than 100 beats/min, thyrotoxicosis, fluid overload, corticoids, atropine, or severe abruptio placentae. No maternal or fetal complications occurred in the 36 patients studied; a well-tolerated tachycardia developed in most patients. Fetal heart rate tracings and pH improved in 32 patients. Thirty-four neonates were delivered in good clinical and metabolic condition. We conclude that terbutaline intravenous bolus 0.25 mg is a safe and efficacious procedure when the proper indications and contraindications are followed. PMID- 2929682 TI - Factors affecting fetal loss in induction of ovulation with gonadotropins: increased abortion rates related to hormonal profiles in conceptual cycles. AB - Thirty-six first-trimester abortions (9.7%), 16 second-trimester abortions (4.3%), 11 ectopic pregnancies (2.9%), and 10 stillbirths (2.7%) occurred in 373 conceptual cycles after gonadotropin induction of ovulation. Fetal wastage was higher in spontaneous pregnancies that occurred before therapy (54.3%, p less than 0.0001) and lower with subsequent spontaneous pregnancies (10.1%, p less than 0.05). Significant risk factors for overall fetal loss during induced ovulation were a continuous rise of estrogen excretion until ovulation (p less than 0.01) and previous abortion (p less than 0.05). For first-trimester abortion, the risk factor was continuous estrogen rise (p less than 0.01); for second-trimester abortion, the risk factors were a low luteal pregnanediol-to estrogen excretion ratio (p less than 0.002), increased age at conception (p less than 0.02), and high baseline estrogen excretion (p less than 0.05). Multiple pregnancy was not significant. The continuous rising estrogen pattern may serve as a marker of abnormal oocyte maturation. We propose that future studies on infertility treatment should report on pregnancy outcome. PMID- 2929683 TI - Mitotic activity in uterine leiomyomas during the menstrual cycle. AB - To investigate the role of the menstrual cycle in the growth of uterine leiomyomas, the mitotic count per 100 high-power fields and the relation of this to the patient's age (30 to 54 years) were examined in tissue sections of leiomyomas from 181 surgically removed myomatous uteri. The mean mitotic count in the secretory phase (12.7 per 100 high-power fields) was significantly higher than that of the proliferative phase (3.8 per 100 high-power fields) (p less than 0.01) or menses (8.3 per 100 high-power fields) (p less than 0.05). We found the highest mitotic count (54 per 100 high-power fields) in a leiomyoma at the early secretory phase. In the secretory phase, the younger age group exhibited a significantly higher mitotic count than the older group. Increased mitotic activity in leiomyomas under the hormonal milieu of the secretory phase of the menstrual cycle suggests that the growth of these tumors is affected by progesterone level. In addition, this study defined the range of mitotic counts occurring in the tissue sections of typical leiomyomas during the menstrual cycle. PMID- 2929684 TI - Causes of the increase in the incidence of ectopic pregnancy. A study on 1017 patients from 1966 to 1985 in Turku, Finland. AB - The relationship between the increased incidence of ectopic pregnancy and the known risk factors of this disorder was examined by 5-year age groups and equivalent calendar periods to determine the causes of the recent "epidemic" of ectopic pregnancy. None of the known risk factors would alone explain the observed increase. Consequently, multivariate analysis by log-linear models was applied: age, past pelvic operation, previous pelvic inflammatory disease, antecedent legal abortion, and current use of an intrauterine contraceptive device were responsible for the increase in the occurrence of the disease. The strongest association with the observed temporal trend in the increase of ectopic pregnancy was found for pelvic operation (including previous ectopic pregnancy), pelvic inflammatory disease, and current use of an intrauterine contraceptive device. Improved diagnosis and changing demographic patterns also contributed to the increase in the annual number of ectopic pregnancies. PMID- 2929685 TI - Whole bowel irrigation during pregnancy. AB - Whole bowel irrigation is a routine colonoscopic preparatory procedure. It has been advocated as a method of cleansing the alimentary canal of poisons after acute overdose. Its use during pregnancy has not been described for either indication. We report a case of an iron overdose during the third trimester treated with whole bowel irrigation without complication. PMID- 2929686 TI - Postpartum bacteremia and placental colonization with genital mycoplasmas and pregnancy outcome. AB - The influence of placental colonization and postpartum bacteremia with genital mycoplasmas on the course of delivery and the immediate postpartum period was evaluated in 511 women who gave birth to live infants of at least 26 weeks' gestation. Genital mycoplasmas were isolated from the placenta in 153 patients (29.9%) and from blood in four patients (0.8%). These four isolates were all Ureaplasma urealyticum. Patients with genital mycoplasmas isolated from the placenta were delivered of infants with birth weights and gestational ages similar to those of infants of patients who did not have genital mycoplasmas in the placenta (3260 gm and 39.2 weeks versus 3272 gm and 39.3 weeks). No adverse effects of maternal postpartum bacteremia with genital mycoplasmas were observed, either in the mother or in the baby. We conclude that, whereas genital mycoplasmas frequently can be isolated from the placenta, there is no evident relationship between the presence of genital mycoplasmas and pregnancy outcome. In a few instances U. urealyticum has been isolated from the blood of afebrile postpartum women. In these women the presence of this bacteria is probably related to the birth process. This bacteremia does not precede an infectious complication. PMID- 2929687 TI - Clinical usefulness of estimation of serum fructosamine concentration as screening test for gestational diabetes. AB - Serum fructosamine levels and fructosamine/protein ratios were measured in 100 pregnant women who underwent glucose tolerance tests because of clinical risk. Compared with normal pregnant women, the 13 study participants with gestational diabetes had higher fructosamine/protein levels (39 +/- 3.9 mumol/gm versus 37 +/ 3.2 mumol/gm, p less than 0.05), fasting serum glucose levels (107 +/- 13.7 mg/dl versus 82 +/- 8.6 mg/dl, p less than 0.001), and area under curve of glucose tolerance test (36 +/- 5 gm x min x dl-1 versus 22 +/- 3.6 gm x min x dl 1, p less than 0.001). The serum fructosamine levels were not significantly different between the two groups of participants (2.3 +/- 0.26 mmol/L versus 2.2 +/- 0.17 mmol/L); 10 of the 13 women with diabetes had a fructosamine/protein ratio within 2 SD of the mean of the groups of normal pregnant women. Spontaneous caloric intakes (r = 0.72, p less than 0.005) and the hospital mean daily capillary glucose levels during diabetic diet (r = 0.72, p less than 0.005) correlated better with the fructosamine/protein ratio than with fasting serum glucose levels (r = 0.58, p less than 0.05) and area under curve (r = 0.57, p less than 0.05). Consequently, serum fructosamine and fructosamine/protein ratio levels should be considered insensitive as a screening test in pregnant patients with clinical risk of gestational diabetes. PMID- 2929688 TI - Endocrine maturation and lung function in premature neonates of women with diabetes. AB - Because respiratory distress syndrome may result, in part, from a hormonal deficiency in the developing fetus, we investigated the endocrine millieu of 28 infants of women with diabetes who were delivered prematurely (34 to 37 weeks of gestation). The umbilical serum concentrations of estrone, estradiol, estriol, cortisol, and prolactin in infants of women with diabetes who developed respiratory distress syndrome (n = 6) were lower than those in infants of women with diabetes who had normal lung function. Serum hormone levels in age-matched newborns of normal women were higher than those in the infants of women with diabetes with respiratory distress syndrome but were not different than those in the infants of women with diabetes with normal lung function. Plasma glucose levels were highest in women whose neonates developed respiratory distress syndrome. An inverse correlation existed between maternal glucose levels and lecithin-sphingomyelin ratios in amniotic fluid. Thus diabetes occasionally results in significantly delayed maturation of the fetal endocrine milieu. In these instances, delayed fetal lung maturation is a frequent occurrence. Moreover, both phenomena may be related to the extent of diabetic control during pregnancy. PMID- 2929689 TI - 2,3-diphosphoglycerate in normal and pathologic pregnancy: relationship to neonatal weight. AB - 2,3-Diphosphoglycerate levels were assayed in 154 pregnant women in third trimester (61 normal, 52 diabetic, 19 with gestational hypertension, 7 with fetal macrosomia, and 15 with idiopathic fetal underdevelopment). A correlation was found between 2,3-diphosphoglycerate levels and birth weight (absolute and relative birth weight or birth weight expressed as percentile), which was negative in normal patients evaluated in the last 7 days before delivery (r = 0.38; p = 0.04) and positive in diabetic patients (evaluated in the third trimester and in the last 7 days before delivery) and in patients with gestational hypertension (evaluated in the third trimester) (r and p values differ according to whether birth weight is expressed as absolute, relative, or a percentile). No correlation was found between 2,3-diphosphoglycerate levels and birth weight in patients with neonatal underdevelopment or macrosomia of unknown origin. On the basis of these results we hypothesize that in some conditions the fetus can influence maternal 2,3-diphosphoglycerate levels and hence its own oxygen supply and growth in utero. PMID- 2929690 TI - Immature (malignant) teratoma of the fallopian tube. AB - Primary immature (malignant) teratoma of the fallopian tube is an extremely rare occurrence. We report such a case, which appears to be the third reported in the literature. PMID- 2929692 TI - Changes in peripheral venous tone before the onset of hypertension in women with gestational hypertension. AB - Forearm venous tone was measured throughout pregnancy in 68 nulliparous women thought to be at high risk of the development of gestational hypertension. Normotensive pregnancy was associated with a progressive venodilatation. Gestational hypertension subsequently developed in 12 women. Before the onset of hypertension, these 12 women showed a greater degree of venodilatation, compared with women who remained normotensive throughout their pregnancies (p less than 0.001). As the hypertension became manifest, the women became relatively venoconstricted (p less than 0.001). Simple, noninvasive measurements of forearm venous tone provide important information about the pathophysiology of gestational hypertension and may be useful in the detection of women who are at increased risk. PMID- 2929691 TI - Early hypothyroidism in patients with menorrhagia. AB - The functional status of the thyroid gland was evaluated in 67 apparently euthyroid menorrhagic women by a thyrotropin-releasing hormone test. Fifteen of 67 showed mild primary hypothyroidism characterized by a small but significant elevation of basal levels of thyroid-stimulating hormone (5.9 +/- 0.76 versus 2.4 +/- 0.24 mU/L) and lowering of serum thyroxine levels (85 +/- 4.2 versus 105 +/- 3.0 nmol/L) to levels that were nevertheless within the normal range and exaggerated response of serum thyroid-stimulating hormone and thyroxine to administration of thyrotropin-releasing hormone. Triiodothyronine levels showed no significant change. The terms early and potential hypothyroidism appear to better describe the preliminary phases of hypothyroidism than do other terms in current use. Menorrhagia disappeared within 3 to 6 months and did not reappear in 1 to 3 years of follow up in all patients with early hypothyroidism to whom L thyroxine was given. This was accompanied by a significant decline in random serum thyroid-stimulating hormone levels and rise of thyroxine levels to those found in the group with a negative response to the thyrotropin-releasing hormone test, with no change in levels of triiodothyronine. Further systematic study of thyroid function in menorrhagia is warranted. PMID- 2929693 TI - Placental isoferritin: a new serum marker in toxemia of pregnancy. AB - The serum concentrations of placental isoferritin and normal ferritin were determined in 20 patients with preeclamptic toxemia of pregnancy and were compared with the level measured in normal pregnant women at the third trimester and in labor at term. The mean serum concentration of placental isoferritin for the women with preeclamptic toxemia was found to be low: 7.5 +/- 23 U/ml compared with 81.6 +/- 89.3 U/ml in normal pregnancy during the third trimester and 54.8 +/- 53 U/ml in term delivery. In comparison, there was no significant difference in the serum levels of normal ferritin in both pregnant women with toxemia and in those without toxemia. These results suggest that placental isoferritin may be a useful marker for preeclamptic toxemia of pregnancy. PMID- 2929694 TI - The effects of acute alcohol intoxication on biophysical activities: a case report. AB - A computer-assisted biophysical assessment was performed in a woman with chronic alcoholism at 37 weeks' gestation. She was first seen in a state of acute alcohol intoxication (322 mg/dl). Although fetal breathing movement incidence was normal (30%), fetal tachypnea (67 breaths per minute) and decreased fetal body movements (0.11%) were seen. Because these findings differ from those previously reported with regard to normal pregnancies exposed to lower levels of alcohol, their implications are discussed. PMID- 2929695 TI - Nonstress testing with acoustic stimulation and amniotic fluid volume assessment: 5973 tests without unexpected fetal death. AB - In a 36-month period antepartum testing was performed 5973 times in 2628 women with singleton high-risk pregnancies. The testing scheme involved a modified nonstress test with sound stimulation. Testing was performed twice weekly for patients with diabetes (classes B through R), gestational age exceeding 42 weeks, and documented intrauterine growth retardation, and weekly for other indications. If no spontaneous acceleration was observed within 5 minutes, a single 1- to 2 second sound stimulus was applied to the lower maternal abdomen with an artificial larynx. If necessary, a second sound stimulation was applied within 10 minutes. In addition all patients received ultrasonographic four-quadrant assessment of amniotic fluid volume. The mean testing time was 10 minutes. Only 2% of tests were nonreactive with sound stimulation. Seventeen percent of nonstress tests that were nonreactive with sound stimulation were followed by positive results of a contraction stress test or a biophysical profile score less than or equal to 4. The overall intervention rate was 3%. All fetuses with a single acceleration only eventually met criteria for negative results to a contraction stress test or had a biophysical profile score greater than or equal to 8. There were no unexpected antepartum fetal deaths. Sound-induced accelerations appear to be valid in the prediction of fetal well being, and the use of sound stimulation results in a significant shortening of testing time. Simultaneous assessment of amniotic fluid volume may reduce the risk of fetal death to a negligible level. PMID- 2929696 TI - Correcting umbilical artery flow velocity waveforms for fetal heart rate is unnecessary. AB - We prospectively examined 55 normal pregnant women between 32 and 41 (means = 37) weeks' gestation. Five measurements of the umbilical artery peak-systolic/end diastolic frequency ratio were obtained from each patient during one examination. Comparison of the fetal heart rate and the umbilical artery peak-systolic/end diastolic frequency ratios between pregnancies less than 37 and greater than 37 weeks' gestation revealed no difference. Subsequently a total of 256 measurements were analyzed as one group. Plotting the individual peak-systolic/end-diastolic frequency ratios against the corresponding fetal heart rates revealed a moderate negative linear correlation: y = 4.15-0.012x, r = -0.36 and p less than 0.04. When only heart rates between 120 to 160 beats/min were plotted against peak systolic/end-diastolic frequency ratios, a weaker correlation was found (r = 0.33, p = 0.15). The difference (mean +/- SD) between the obtained and the corrected peak-systolic/end-diastolic frequency ratios was 4.4% +/- 3.2%. The 95th percentile of the obtained peak-systolic/end-diastolic frequency ratio was 3.35 and the corrected ratio was 3.27. Averaging of the five measurements obtained from each patient for all 55 patients decreased the 95th percentile value to 3.09 whereas the same procedure for the corrected peak-systolic/end diastolic frequency ratios decreased it to 3.07. We conclude that although there is a statistically significant negative linear correlation between the fetal heart rate and the umbilical artery peak-systolic/end-diastolic frequency ratio, this relationship is not clinically significant. PMID- 2929697 TI - The ontogeny of growth hormone in the human fetal pituitary. AB - To examine the ontogeny of growth hormone synthesis and secretion in human fetus, growth hormone messenger ribonucleic acid was measured in 11 pituitaries from fetuses of 16 to 27 weeks of gestation by hybridization of cytosol ribonucleic acid with complementary deoxyribonucleic acid labeled with phosphate 32. Pituitary growth hormone content and serum growth hormone, thyroxine, and cortisol concentrations were assessed by radioimmunoassay. Growth hormone messenger ribonucleic acid content in the fetal pituitary increased from the early midtrimester, reaching a level 15.3 times higher at 27 weeks of gestation than the value at 16 weeks. However, growth hormone content in the pituitary showed no evident change during 16 to 21 weeks of gestation and started to increase after 22 weeks. Serum concentration of growth hormone was variable but always greater than 50 ng/ml, and the maximal level was observed at 20 weeks of gestation (141 ng/ml). Although serum thyroxine concentration in the fetuses showed no correlation with pituitary growth hormone content or serum growth hormone concentration, serum concentration of cortisol was correlated positively with growth hormone content in the fetal pituitary. These results suggest that the maturation of the growth hormone synthesis and secretion system in the fetal pituitary occurs after 22 weeks of gestation and that cortisol may play some role in the ontogenesis of growth hormone. PMID- 2929699 TI - Determination of pentamidine transfer in the in vitro perfused human cotyledon with high-performance liquid chromatography. AB - Pentamidine is used to treat Pneumocystis carinii pneumonia. The incidence of this infection in pregnancy has paralleled the increasing incidence of acquired immunodeficiency syndrome in pregnancy. Using the in vitro bidirectionally perfused human placenta, we studied the transfer of pentamidine across the placenta. Pentamidine was added to the maternal circulation at therapeutic concentrations (2 micrograms/ml). No transfer of pentamidine was detectable with a newly devised high-performance liquid chromatography method sensitive to 0.05 micrograms/ml of pentamidine. Increasing the pentamidine concentration tenfold produced a low level of transfer to the fetal circuit. Fetal concentrations were far below maternal perfusate concentrations. Placental tissue levels were higher than media levels. These data are suggestive of minimal drug transfer to the fetus and significant concentration of the drug in placental tissue. PMID- 2929698 TI - Effect of food withdrawal on arterial blood glucose and plasma 13,14-dihydro-15 keto-prostaglandin F2 alpha concentrations and nocturnal myometrial electromyographic activity in the pregnant rhesus monkey in the last third of gestation: a model for preterm labor? AB - Pregnant rhesus monkeys were studied between 109 and 149 days of gestation. Food withdrawal for 48 hours (with free access to water) was accompanied by a decrease in maternal whole blood glucose concentration and an increased maternal arterial plasma 13,14-dihydro-15-keto-prostaglandin F2 alpha concentration. On successive nights of the 48-hour period of food withdrawal, there was an increase in the frequency of myometrial contractions as recorded by uterine electromyogram. In the period after food was returned, blood glucose, arterial 13,14-dihydro-15-keto prostaglandin F2 alpha concentration, and contraction frequency returned to baseline. Because food withdrawal results in the appearance of the nocturnal contraction pattern seen at term, we suggest that this experimental paradigm may be used as a model for preterm labor. PMID- 2929700 TI - Pharmaceutical-supported supplements. PMID- 2929701 TI - The management of early labor. PMID- 2929702 TI - The epidemiology of Acanthamoeba keratitis in the United States. AB - We surveyed members of the Ocular Microbiology and Immunology Group and reviewed laboratory requests at the Centers for Disease Control to determine better the epidemiology of Acanthamoeba keratitis in the United States. A total of 208 cases of Acanthamoeba keratitis were identified. The number of cases increased gradually between 1981 and 1984, with a dramatic increase beginning in 1985. Males and females were equally affected. Of the 208 patients, 85 (41%) resided in California, Texas, Florida, or Pennsylvania. Of 189 patients, 160 (85%) wore contact lenses, predominantly daily-wear or extended-wear soft lenses. Of the 138 patients who wore contact lenses and for whom information was available, 88 (64%) used saline prepared by dissolving salt tablets in distilled water. Patients aged 50 years and older were more likely to have had a history of trauma than younger patients, and males were more likely to have a history of trauma than females. PMID- 2929703 TI - Long-term results of cryotherapy on malignant epithelial tumors of the conjunctiva. AB - We studied the results of combined treatment with excision and cryotherapy with the nitrous oxide probe in 22 eyes of 20 patients with intraepithelial tumors or squamous cell carcinomas of the conjunctiva. Patients were followed up for five to 12 years. Only two recurrences (9%) were seen, both of which occurred within the first two years. Over the long term, excision combined with cryotherapy decreased the recurrence rate of intraepithelial tumors and squamous cell carcinomas of the conjunctiva. PMID- 2929704 TI - Investigation of an outbreak of Moraxella conjunctivitis at a Navajo boarding school. AB - In 1986, an outbreak of Moraxella follicular conjunctivitis occurred in girls attending a Navajo boarding school in New Mexico. We diagnosed 19 cases of culture-proven, and 21 of clinical conjunctivitis based on isolation of Moraxella from conjunctival cultures and the occurrence of symptoms significantly associated with positive culture. Sharing eye makeup was significantly associated with Moraxella-positive conjunctivitis (odds ratio [OR] = 7.2, P = .004) and showed a trend toward significance in those with clinical conjunctivitis (OR = 2.9, P = .09). Eyeliner and eye shadow were implicated (OR = 4.1, P less than .05). We cultured samples of 13 students' makeup; one third of the eyeliners were positive for Moraxella. Nasal carriage of Moraxella was found in 35 (44%) of the 79 female boarders and in 20 (21%) of 97 Navajo patients at two nearby clinics. In a prospective evaluation of the effect of patient education and rifampin therapy on the occurrence of conjunctivitis during an 11-month follow-up period, both types of intervention were successful in significantly reducing the rate of conjunctivitis when compared with that in a control group. PMID- 2929705 TI - Ophthalmic solutions, the ocular surface, and a unique therapeutic artificial tear formulation. AB - In rabbit studies, we found that extended exposure of the ocular surface to existing ophthalmic solutions resulted in gross surface abnormalities and decreases in conjunctival goblet cell density. We developed an electrolyte solution (solution 15) that preserves normal gross appearance, goblet cell density, corneal epithelial glycogen levels, and ocular surface morphologic characteristics after extended exposure to the rabbit ocular surface. We created an artificial tear formulation by adding a demulcent and a buffering system to solution 15 and reducing its osmolarity to 162 mOsm/l. We then compared our artificial tear formulation to Hypotears in a double-masked, crossover study involving 11 patients with dry-eye disorders. Our artificial tear formulation was more effective than Hypotears in decreasing tear film osmolarity and rose bengal staining, and was preferred subjectively by an eight-to-one margin. PMID- 2929706 TI - The site of operating microscope light-induced injury on the human retina. AB - We determined the site of the focal illumination from the Zeiss OPMI-6 operating microscope on the retina of the phakic and aphakic human cadaver eye by directly observing the illuminating element image on the posterior scleral surface of the globe. With the eye straight ahead and the operating microscope level, the focal oval area of retinal illumination was located superior to the foveola in both the phakic and aphakic eye. Tilting the operating microscope 10 degrees toward the surgeon displaced the entire illuminating element image 0.50 mm below the foveola in the phakic eye and 0.25 mm below the foveola in the aphakic eye. Rotating the eye inferiorly 10 degrees displaced the entire illuminating element image 1.0 mm below the foveola in the phakic eye and 1.25 mm below the foveola in the aphakic eye. Centering the field of view superiorly (viewing the superior limbus) paradoxically displaced the illuminating element image inferiorly, resulting in central foveal illumination. Foveal light exposure was avoided in most eye positions by tilting the microscope at least 10 degrees toward the surgeon. PMID- 2929707 TI - Evaluation of phototoxic retinal damage after argon laser iridotomy. AB - We performed several visual function tests in 17 eyes (ten patients) before and after argon laser iridotomy in an effort to detect diffuse photochemical damage to photoreceptors caused by exposure to the intense, blue-green light that is transmitted into the posterior segment as the iridotomy is created and enlarged. No change was detected in static threshold sensitivity in the central 30 degrees of the field (Octopus perimeter), color sensitivity (Farnsworth-Munsell 100-Hue test), or visual acuity. Contrast sensitivity showed a small increase at low spatial frequencies and a small decrease at high spatial frequencies. The latter change was small and not necessarily laser related, but precautions to limit laser exposure of the posterior pole are prudent. PMID- 2929708 TI - The effect of pterygia on contrast sensitivity and glare disability. AB - To detect subtle changes in visual acuity, we measured spatial contrast sensitivity in 12 patients with pterygium (Group 1) and compared their results with those from an age- and sex-matched control population (Group 2). Glare disability was also measured in each group. Measurements of contrast sensitivity were lower in Group 1 at all spatial frequencies than those of Group 2, independent of the testing device used. Glare disability was significantly increased in Group 1 compared to Group 2. Our studies indicate that contrast sensitivity and glare disability testing may provide additional objective methods for documenting impaired vision in patients with pterygium when Snellen visual acuity is minimally affected. PMID- 2929709 TI - An evaluation of the Tono-Pen for the measurement of diurnal intraocular pressure. AB - We evaluated the Oculab Tono-Pen for potential value in the measurement of diurnal intraocular pressure. Repeated recordings every ten minutes on the same eyes suggested that the instrument provides reproducible information. However, comparisons with Goldmann applanation tonometric measurements, in both single determinations and eight-hour diurnal recordings, showed considerable variation. Correction factors, using either the mean difference in paired readings from the single measurement study or individual differences from the initial set of diurnal recordings, did not eliminate this lack of correlation between measurements with the two instruments. PMID- 2929710 TI - Increase of the short-term fluctuation of the differential light threshold around a physiologic scotoma. AB - Because determination of the differential light threshold of a visual field is a psychophysiologic test, the results can be subject to variation. This scatter measured during a single examination is usually called the short-term fluctuation. Increases of the short-term fluctuation were thought to occur primarily in abnormal visual fields; however, we found an increase of the short term fluctuation in normal visual fields when the measurements were made at the border of a physiologic scotoma, such as the blind spot. These results suggest that an increase of the short-term fluctuation may be mainly related to measurements done with any static perimeter at the border of a depression of the island of vision. PMID- 2929711 TI - The multiple evanescent white-dot syndrome with acute blind spot enlargement. PMID- 2929712 TI - Leber's congenital amaurosis with marbelized fundus and juvenile nephronophthisis. PMID- 2929713 TI - Silicone intraocular lens power vs temperature. PMID- 2929714 TI - Syphilitic interstitial keratitis masquerading as staphylococcal marginal keratitis. PMID- 2929715 TI - Pediatric moisture chambers. PMID- 2929716 TI - Topographic analysis and visual acuity after radial keratotomy. PMID- 2929717 TI - Congenital idiopathic microcoria. PMID- 2929718 TI - Failure of preenucleation radiation to decrease uveal melanoma mortality. The Collaborative Ocular melanoma Study Steering Committee. PMID- 2929719 TI - Developing information-seeking skills in occupational therapy students. AB - This paper discusses the importance of teaching occupational therapy students methods for finding information in libraries. It details the efforts at Ohio State University to supply this instruction and demonstrates the positive results of library user education as seen by the instructors of occupational therapy students. This partnership between librarians and classroom instructors can easily be adapted to any health sciences education program. PMID- 2929720 TI - Rehabilitation of extensor tendon injury of the hand by means of early controlled motion. PMID- 2929722 TI - Not by age alone: gerontology as a specialty in occupational therapy. PMID- 2929721 TI - Grip strengthening with adapted computer switches. AB - The computer grippers have been successful in providing an easily operated, enjoyable, purposeful activity for end-stage grip strengthening for patients preparing to return to heavy industry. Because computer games maintain the patient's attention for long periods, this adaptation is excellent for building endurance. PMID- 2929723 TI - Affective responses to activities: a comparative study. AB - The purpose of this study was to document variation in affective responses to different types of traditional occupational therapy activities. Each of 45 subjects (24 psychiatric inpatients and 21 matched control subjects) participated in a series of four activities: leather lacing, working with clay, filing, and exercycling. Immediately following each activity, each subject completed the Affective Self-Report Checklist designed to elicit affective responses. In addition, each of the activity sessions was professionally videotaped and later rated for affective responses by trained observers. The data analysis revealed no significant differences in affective responses to activities between groups. However, with the groups combined, significant differences were found in affective responses on 6 of the 15 scales of the checklist, with clay and filing the pair of activities that differed most. These findings are a necessary first step in the collection of baseline data regarding responses to activities. PMID- 2929724 TI - Occupational disruption and adaptation: a study of house fire victims. AB - House fires are the most common disasters in our society. Disaster theorists acknowledge that complex daily living problems impede the recovery of victims. However, these problems have not been described in detail. The author conducted a qualitative study of the disruption to daily living routines caused by house fires and of the adaptation process victims undertook to reestablish effective patterns of purposeful activity. The data-gathering methods included observation on the scenes of 15 house or tenement fires and in-depth interviews with members of 10 families displaced by fires. Disruption was found to occur in the victims' use of time and comfort in their personal environment. A data analysis revealed a new process of occupational adaptation. The roles of tasks and activities were determined to be important in recovery. PMID- 2929725 TI - Marital quality, depression, and inconsistent parenting: relationship with observed mother-child conflict. AB - In a study of 47 intact families with two same-sex children, associations among parental depression, marital satisfaction, family conflict, and inconsistent child rearing practices were examined, both between parents and within individual parents. Results are discussed in terms of gender-related differences in family process. The need for further research on father-child interactions is highlighted. PMID- 2929726 TI - Family therapy for learning disabled children. PMID- 2929727 TI - Medication vs behavior management. PMID- 2929728 TI - Family support programs: catalysts for change. AB - The burgeoning family support movement is described in the historical context of the social service and self-help modalities that presaged it and in the context of the current social and political conditions in which it has arisen and to which it is, in part, a response. Challenges faced by the family resource movement, and implications of the movement for professionals and for the present human service delivery system, are examined. PMID- 2929729 TI - State family support and education programs: lessons from the pioneers. AB - More state governments are developing publicly supported preventive programs to strengthen families. This article describes the forces driving these initiatives, which in turn are redefining ideas about when public involvement with families is appropriate. It discusses four state programs and outlines the choices and issues policy makers faced in formulating and implementing them. PMID- 2929730 TI - Suicidal behavior in "normal" adolescents: risk and protective factors. AB - Risk and protective factors were examined in suicidal and nonsuicidal public high school students. With life stress and depression as independent risk factors, family cohesion was found to offset the effect of stress, and friendships to have a more indirect effect. Differential effects of ten sources of stress were analyzed from a developmental perspective, and the probability of suicidal behavior associated with clusters of factors was estimated for the general population. PMID- 2929732 TI - The emergence of dental anthropology. PMID- 2929731 TI - Neonatal behavior and early temperament: a longitudinal study of the first six months of life. AB - Two stable clusters of parent-rated temperamental traits, a "drive" and a "regulatory" cluster, are identified in the first six months of life. The relationship among these clusters and neonatal behavior, measured on the Brazelton Neonatal Behavior Assessment Scale, is considered, and the nature of the clusters compared to the results of other studies with similar methodology. Implications of these results for an interactional theory of early development are discussed. PMID- 2929733 TI - Morphological and metrical comparison of San and Central Sotho dentitions from southern Africa. AB - Comparative morphological and metrical study of San and Central Sotho dentitions indicates that the teeth of the two samples are significantly different from one another. The San dental complex contains traits that add mass to the occlusal surface of microdontic dentitions: moderate low-grade UI1 (13.5%) and UI2 shoveling (24.7%), high Bushman canine (43.1%), fairly low UM2 hypocone reduction (23.3%), high UM2 cusp 5 (55.6%), high LM1 cusp 7 (35.2%), LM1 distal trigonid crest (7.1%), and LM2 deflecting wrinkle (5.3%), lack of reduction of LM1 and LM2 cusp number, in the presence of very low UM1 Carabelli's trait (6.7%) and high LM2 Y-groove (86.3%). Culturally, males occasionally exhibit filed UI1 and females are missing LI1. Conversely, mesodontic Central Sotho dentitions display a more simplified morphology, with the exception of moderately high incidence of UM1 Carabelli's trait (41.0%) and very high LM1 cusp 7 (71.3%). Discriminant analysis of mesiodistal and buccolingual diameters and tooth crown surface area data for the left maxillary teeth supports classification of San dentitions as microdont and Central Sotho dentitions as mesodont. Additionally, metrical analysis indicates that San teeth are more sexually dimorphic than are those of Central Sotho. PMID- 2929734 TI - Complex segregation analysis of dental morphological variants. AB - A set of 20 morphological variants of the dental crowns and four characteristics of the jaws are tested for probable mode of inheritance using the complex segregation analysis method of Morton et al. (Am. J. Hum. Genet. 23:602-611, 1971). Models tested include three two-allele single-locus models (dominant, codominant, and recessive) and a model employing the polychotomized normal distribution of liability (an additive polygenic model), with transmissibility estimated via maximum likelihood. Most of the traits studied are observed using ordinal scales with several grades, and many are tested using more than one dichotomy of their scale. These multiple analyses allow for an examination of such factors as trait incidence on the results of the statistical analysis. The results of the analysis yield propositions of major genes for 13 of the 24 traits examined. Two traits give good evidence of being polygenic in origin. The remaining nine characters present methodological problems that do not allow for a definite conclusion on their mode of inheritance at this time. The ability to test varying levels of transmissibility in the polygenic model allows for an estimation of the percentage of trait variance determined by familial factors. Estimates of transmissibility for all characters examined range from 0 to 1, with a mean of 0.36. These findings may suggest a large environmental role in the development of dental crown morphology. However, the possibility exists that difficulties in the ability to classify the expression of certain traits consistently result in overestimates of the environmental influences on the development of those characters. PMID- 2929735 TI - Human occlusofacial form commonality: race-related traits, ontogeny, paedomorphism, and functional correlates. AB - Previous cephalometric studies of occlusofacial angular and metric data show small variability within and between population samples of Caucasian children and adults. Comparable results were obtained by use of standardized X-ray cephalometry and direct craniometric measurements of skulls of mature specimens of Alouatta caraya and Cebus capucinus. These data measure facial and occlusofacial form and form relationships. Identical measuring techniques are applied to compare data derived from headplates of 19 young adult American Caucasians and 19 articulated Hindu skulls of mature individuals. The data are expanded to include measurements that relate symphyseal form to occlusal and nasomaxillary structure. The facial plane and an "internal" facial plane (nasion to a point tangential to the superior genial tubercles) straddle the mandibular symphysis. The angles they form at nasion and at their intersections with the maxillary occlusal plane were derived and statistically analyzed. The occlusal plane intersect angles show small absolute variability and are not significantly different (P greater than .05) in the two groups. The nasion plane angles are significantly different (P less than .025), reflecting sample differences in facial height. Linear measurements confirm a considerably larger dentoalveolar prognathism in the Hindu group. Data derived from the geometrically averaged tracings of Bjork, Broadbent, Sassouni, and Solow provide further evidence of occlusofacial form commonality. These shared phyletically conservative traits are evidence of highly integrated morphological adaptations for the attainment, maintenance, and functioning of the species-wide pattern of precisely fitting complementary crowns and crown parts that constitute the dental occlusion. PMID- 2929736 TI - Three-dimensional analysis of the maxillary first molar crowns of Canadian Inuit. AB - The maxillary first molar crowns of 48 male and 38 female Canadian Inuit (Eskimos) were analyzed three-dimensionally by using moire contourography methods. Cusp heights were significantly higher in males while the mesial and distal marginal ridges were more proximally placed in males. The metacone and the oblique ridge appeared to be better developed in the males. Comparison of the present results with published results for Dutch and Japanese indicated that the Japanese and Inuit had lower cusps that were more widely spaced than the Dutch. Correlation coefficients suggest that height measurements were positively correlated as were linear measurements. However, there were few significant correlations between height and linear determinations, suggesting that the development of the "width" of a crown is nearly independent of the development of the height of the cusps and crown. PMID- 2929738 TI - Evolution of human serial pairbonding. AB - Data on divorce taken for all available years between 1947 and 1981 from the Demographic Yearbooks of the United Nations on 58 peoples illustrate that divorce has a consistent pattern. Divorces exhibit a skewed distribution, characterized by the occurrence of the mode early in marriage (with a divorce peak on or around the fourth year) and a gradual, long-tailed decline following this peak. Divorce risk peaks in age category 25-29 for males and age categories 20-24 and 25-29 for females, the height of reproductive and parenting years, and divorce counts peak among couples with two or fewer children. These properties of divorce are unrelated to divorce rate; they occur in societies with both high and low divorce rates. Data on available horticultural and gathering/hunting societies illustrate that divorce also peaks among young couples early in marriage. Remarriage by divorced and widowed individuals of reproductive age is also common cross culturally. It is proposed that the above four-year modal marriage duration among couples of reproductive age who divorce reflects a hominid reproductive strategy that probably evolved some time after the appearance of Homo in response to increased female "reproductive burden" and functioned to ensure the survival of the hominid infant through weaning. Serial pairbonding during the female's reproductive years had ancestral adaptive advantages, producing the modern cross cultural pattern of serial pairbonding. PMID- 2929737 TI - Caries prevalences among geochemical regions of Missouri. AB - Our objectives were to determine how the prevalences of caries in elementary school children vary between geochemically defined regions of the state of Missouri and to compare this variation with that found for prehistoric Missouri inhabitants (Hildebolt et al.: Am. J. Phys. Anthropol. 75:1-14, 1988). Caries data on 6,584 school children were used in the study of second and sixth graders drinking optimally and suboptimally fluoridated water. Geochemical regions were based on maps recently published by the United States Geological Survey. Differences in mean caries scores and proportions of children with caries were tested by analysis of covariance, analysis of variance, Student t, and chi squared tests. We found that caries prevalences do vary between the geochemical regions of the state. In the total sample, however, there were no significant differences between those children drinking optimally fluoridated water and those drinking suboptimally fluoridated water. We conclude that there is variation in caries rates among geochemically defined regions of the state and that geochemical factors associated with young parent materials may be antagonizing the action of fluoride. PMID- 2929739 TI - The spread of exclusive mating in a chacma baboon population. AB - Mating has progressively tended toward pair bonding in a chacma baboon (Papio cynocephalus ursinus) population during eight years of study. Both males and females have been mating with a smaller and smaller percentage of the potential mates available to them. Troop subdivision during the dry winter in the absence of predation was the original cause of mating limitation, but most members of winter subtroops only rarely mated with adults who had not belonged to the same winter subtroop during the summers as well. Following reintroduction of potential predation, both subtroop size and frequency decreased, but mating did not become less exclusive. PMID- 2929740 TI - Engis: preparation damage, not ancient cutmarks. AB - Scratches found on the Engis 2 cranium have been described as perimortem and interpreted as intentional scalping marks by Russell and LeMort (Am. J. Phys. Anthropol. 69:317-323, 1986). These marks are described and compared to damage on other fossil hominids. The Engis marks have been misinterpreted. These marks are sandpaper striae formed during restoration of the vault, moulding striae formed when mold part lines were incised into the fossil and profiling striae formed when craniograms were made with sharp steel instrument tips. None of them have anything to do with prehistoric behavior. PMID- 2929741 TI - The calcaneus of Australopithecus afarensis and its implications for the evolution of bipedality. AB - Calcanei from African apes, modern humans, and Australopithecus afarensis are compared to investigate the anatomical and mechanical changes that occurred in this bone as a result of the transition to terrestrial bipedality. Features analyzed include the cross-sectional area and volume of the calcaneal tuber, the geometry and orientation of the articular surfaces, and the surface topography of the calcaneal corpus. Calcaneal morphology is unequivocal in its partitioning of quadrupedal pongids and bipedal hominids. PMID- 2929742 TI - Creeping patterns of human adults and infants. AB - The patterns of swing and support for the hands-and-feet or hands-and-knees gaits (creeping) of human adults and infants are compared based on data from a number of studies. Human infants show considerable variability in their creeping gait patterns, whereas adult patterns are less variable and fairly consistent after a few minutes of practice. Creeping on hands-and-knees appears to dictate a gait pattern characteristically different from creeping on hands-and-feet. The highly inefficient nature of adult creeping supports the view that our early hominid ancestors were poorly adapted to quadrupedal locomotion. Data obtained from high speed film analysis of human creeping patterns show that the number of foot lengths per stride in creeping is about twice that for normal upright walking at the same speed. The support pattern of human creeping is different from that of nonhuman primates. These findings are discussed in the context of debate concerning the origin of the Laetoli hominid footprints and the knuckle-walking hypothesis. PMID- 2929743 TI - The anterior buccal mandibular depressions: ontogeny and phylogeny. AB - The frequency of an anterior buccal depression in the mandible (ABMD), or a mental fossa, is reported on 970 human mandibles of various groups and different ages, as well as in 38 mandibles of nonhuman primates. The ontogenetic and phylogenetic significance of the results relevant to development of a chin in Homo sapiens is discussed. The ABMD is also compared with the occurrence of a lingual mandibular depression. PMID- 2929744 TI - Postcardiotomy delirium: conclusions after 25 years? AB - Although postcardiotomy delirium has been studied widely, there are few data about the current prevalence, compared to that reported in the late 1960s. There have been few efforts to replicate early observations. The authors review the literature using meta-analysis to combine the results of 44 studies. They examined the relationships between postcardiotomy delirium and 28 hypothesized risk variables. The prevalence of postcardiotomy delirium has remained fairly constant over time at 32%. There was no difference in the total prevalence of postcardiotomy delirium reported in studies that used interviews versus chart reviews. Sex, previous psychiatric illness, intelligence, and time on bypass failed to correlate with postcardiotomy delirium, and age correlated with it only slightly. Correlation coefficients of more than 0.30 were found only for noncongenital heart disease and postoperative EEG abnormality. Preoperative psychiatric intervention had the highest correlation with postcardiotomy delirium (r = -0.60). PMID- 2929745 TI - The diagnostic implications of formal thought disorder in mania and schizophrenia: a reassessment. AB - The authors compared nine manic patients exhibiting formal thought disorders (tangentiality, neologisms, drivelling, private use of words, and paraphasias) with 102 manic patients without these thought disorders and with 31 schizophrenic patients. Manic patients with formal thought disorders tended to have more "schizophrenic" symptoms than did manic patients without formal thought disorders, but both groups improved significantly more during the index episode than did the schizophrenic patients. Although the prevalence of flight of ideas was high in mania, narrowly defined formal thought disorder was rare, suggesting that precise definition and description of thought disorders would be helpful in distinguishing mania from schizophrenia. PMID- 2929746 TI - Temporal lobe pathology in schizophrenia: a quantitative magnetic resonance imaging study. AB - Although numerous studies have confirmed the presence of larger cerebral ventricles in schizophrenia, the locus of tissue loss remains elusive. By analyzing magnetic resonance scans with computerized image analysis, the authors determined gray and white matter volumes in the temporal lobes and prefrontal regions of 17 patients with schizophrenia and 17 age- and sex-matched normal subjects. The volume of temporal lobe gray matter was 20% smaller in the patients than in the control subjects. The lateral ventricular volume was 67% larger in the patients and, when normalized for brain size, correlated inversely with the volume of temporal lobe gray matter. PMID- 2929747 TI - HPA axis hyperactivity and recovery from functional psychoses. AB - Some patients with functional psychoses follow a chronic, deteriorating course and others recover; at present clinicians have essentially no established factors beyond diagnosis and chronicity to predict which course a psychotic patient might follow. Because data on diagnostic specificity suggested that the dexamethasone suppression test might provide another, much needed prognostic factor, the authors administered these tests to 98 consecutively admitted patients with nonmanic psychoses. High postdexamethasone cortisol levels (6 micrograms/dl or higher) at baseline predicted recovery from psychosis at 1 year, independent of episode chronicity and diagnosis. Diagnosis did not correspond well to test results but was itself an important predictor. PMID- 2929748 TI - Clinical status and emotional adjustment of children of depressed mothers. AB - The authors compared children (ages 7-13 years) of unipolar depressed mothers with children of nondepressed psychiatric patients, of nondepressed medical patients, and of nondepressed mothers in the community. The children's adjustment was rated by clinicians on the Child Adjustment Schedule and by the mothers on the Child Behavior Checklist. The highest proportion of clinically significant problems was found in the children of the depressed mothers. However, the overlap between the problems of these children and those of the children of the nondepressed psychiatric patients calls into question the formulation that children's adjustment difficulties are specific to parental depression. PMID- 2929749 TI - Life events of adolescents in relation to personal and parental substance abuse. AB - The author examined the life events reported by 138 adolescents in relation to their own and their parents' alcohol and/or drug use. The 62 adolescents who were substance abusers reported more negative events involving deviance and emotional distress and evaluated the life events they experienced as less desirable than did the 76 nonabusing adolescents. Substance-abusing adolescents and the 31 nonabusing adolescents with substance-abusing parents experienced comparable numbers of stressful life experiences; however, the type and qualitative features of the events differed. Adolescents with substance abuse in only one family generation experienced more emotional distress than those with substance use patterns consistent across generations. PMID- 2929750 TI - Childhood trauma in borderline personality disorder. AB - Subjects with borderline personality disorder (N = 21) or borderline traits (N = 11) and nonborderline subjects with closely related diagnoses (N = 23) were interviewed in depth regarding experiences of major childhood trauma. Significantly more borderline subjects (81%) gave histories of such trauma, including physical abuse (71%), sexual abuse (68%), and witnessing serious domestic violence (62%); abuse histories were less common in those with borderline traits and least common in the subjects with no borderline diagnosis. These results demonstrate a strong association between a diagnosis of borderline personality disorder and a history of abuse in childhood. PMID- 2929751 TI - Personality disorder in the families of depressed, schizophrenic, and never-ill probands. AB - In a blind family study of 176 probands with nonpsychotic major depression, psychotic major depression, schizophrenia, or no history of DSM-III disorders, only the relatives of depressed probands with mood-incongruent psychotic features had a risk for personality disorders higher than that for the relatives of never ill probands. The authors did not find a high rate of borderline personality in relatives of depressed probands or of schizotypal personality disorder in relatives of probands with schizophrenia or any psychosis. However, depressed probands with normal dexamethasone test results had a significantly higher familial loading for the DSM-III cluster of histrionic, antisocial, borderline, and narcissistic personality disorders. PMID- 2929752 TI - Ability to form an alliance with the therapist: a possible marker of prognosis for patients with antisocial personality disorder. AB - Antisocial personality disorder is generally perceived to be refractory to treatment, particularly psychotherapy. In this study, the ability of 48 patients with this disorder to form a working relationship with a psychotherapist or drug counselor was examined in relation to outcome of 24 weeks of treatment evaluated at 7-month follow-up. Some antisocial patients were able to form working relationships with their therapists, and there was a significant association between the ability to form such a relationship and treatment outcome. Measures of this ability, such as the Helping Alliance Questionnaire, may help identify antisocial patients who can benefit from psychotherapy. PMID- 2929753 TI - Infrequent occurrence of EEG abnormalities in panic disorder. AB - EEG abnormalities have been frequently reported in patients with panic disorder, although controlled studies are lacking. The authors examined the EEGs of 35 consecutively evaluated, medication-free patients with panic disorder and found that only five (14%) had nonspecific abnormal EEGs and none displayed EEG evidence supportive of an ictal process. The presence or absence of EEG abnormalities was not significantly associated with the presence or absence of psychosensory symptoms. Although it is not likely that panic disorder is an epileptiform disorder, temporal lobe and limbic structures probably play a major role in the pathophysiology of panic. PMID- 2929754 TI - Psychosis, aggression, and self-destructive behavior in hospitalized adolescents. AB - The authors studied the history of aggressive and self-destructive behaviors in psychotic and nonpsychotic hospitalized adolescents (N = 137). A multidimensional measure of self- and other-directed aggression was retrospectively applied to each patient's social and developmental history. Nonsignificant gender and diagnostic differences were obtained on ratings of violence and suicide. Broader definitions of internal and external aggression yielded nonsignificant diagnostic differences, but gender differences were observed on both internal and external aggression measures. Females displayed greater internal aggression, and males reported higher external aggression scores. These results, compared to those of other investigators, suggest the importance of social and cultural variables in understanding adolescent psychosis and aggression. PMID- 2929755 TI - High prevalence of visual hallucinations in research subjects with chronic schizophrenia. AB - The authors examined the prevalence of visual hallucinations in severely ill hospitalized research subjects with carefully diagnosed chronic schizophrenia and found it to be high. A chart review of 100 discharged subjects revealed documentation of visual hallucinations in 32%, and a prospective examination of 43 additional subjects revealed a history of visual hallucinations in 56% (N = 24). Also, the fact that in 43% of the patients with visual hallucinations the history of visual hallucinations was first documented during the research ward work-up suggests that clinicians frequently do not inquire about visual hallucinations in patients with chronic schizophrenia. PMID- 2929757 TI - A magnetic resonance imaging study of autism: normal fourth ventricle size and absence of pathology. AB - Magnetic resonance imaging did not diagnose neuropathology in 15 autistic patients. Measurements of the midsagittal area and volume of the fourth ventricle did not differ between these patients and matched control subjects. PMID- 2929756 TI - Benzodiazepine dependence and withdrawal in elderly patients. AB - Severity of withdrawal symptoms and clinical outcome were compared in 19 elderly and 22 younger benzodiazepine-dependent patients matched for benzodiazepine half life, dosage, and duration of treatment. During gradual taper of benzodiazepine doses, the elderly patients showed significantly less severe withdrawal symptoms on several clinical measures and a comparably favorable outcome. Approximately half of each group remained benzodiazepine free for at least 4 weeks. Both groups of patients tolerated drug discontinuation without serious consequences such as seizures or psychosis. Tapered benzodiazepine withdrawal did not appear to be more risky for the elderly group than for the younger patients. PMID- 2929758 TI - Seasonal cocaine abuse. AB - The authors describe two patients with seasonal affective disorder characterized by fluctuations in cocaine craving that paralleled seasonal dysphoria. This extends the range of axis I disorders associated with cocaine self administration. PMID- 2929759 TI - Carbamazepine treatment for benzodiazepine withdrawal. AB - Nine patients were given carbamazepine before rapid discontinuation of benzodiazepines. Most patients had had long-term benzodiazepine treatment and had abused benzodiazepines; five had taken high doses. All patients tolerated rapid discontinuation well and none developed significant withdrawal symptoms. PMID- 2929760 TI - Behavioral hyporeactivity to physostigmine in detoxified primary alcoholics. AB - Changes in anergia/inhibition, mood, and pulse rate induced by intravenous physostigmine were significantly less pronounced in 26 patients with primary alcoholism than in 36 normal control subjects. These results suggest possible abnormalities in central cholinergic functioning in primary alcoholics. PMID- 2929761 TI - Clomipramine-induced pseudocyanotic pigmentation. PMID- 2929762 TI - Methylphenidate for cyclosporine-associated organic mood disorder. PMID- 2929763 TI - Evaluation and treatment of catatonia. PMID- 2929765 TI - Testing of persons at low risk for AIDS. PMID- 2929764 TI - Treatment of monosymptomatic hypochondriacal psychosis with pimozide in an AIDS patient. PMID- 2929766 TI - Delusions of having AIDS. PMID- 2929768 TI - Cyproheptadine in movement disorders. PMID- 2929767 TI - Suicidal tendencies in women with human immunodeficiency virus infection. PMID- 2929769 TI - PTSD and suicide attempts by adolescents. PMID- 2929770 TI - Carbamazepine in panic disorder. PMID- 2929772 TI - Antecedents of "spontaneous" panic attacks. PMID- 2929771 TI - Prevalence of agoraphobia without panic in clinical settings. PMID- 2929773 TI - Should "depression" be dropped the way "neurosis" was? PMID- 2929774 TI - Islamic view of mental disorders. PMID- 2929775 TI - Refinement of the diagnosis of schizophreniform disorder. PMID- 2929776 TI - Adequate trials of pharmacotherapy. PMID- 2929778 TI - Blood-injury phobia. PMID- 2929777 TI - Child protection workers' role in erroneous allegations of child abuse. PMID- 2929779 TI - Role of clinical skill in maintaining a private practice. PMID- 2929780 TI - Criticisms of DSM-III-R. PMID- 2929781 TI - Relationship between anxiety and depression. PMID- 2929782 TI - State versus trait in mental disorders. PMID- 2929784 TI - "Somatization" of psychiatric disorders. PMID- 2929783 TI - Plasma dexamethasone levels and disagreement between the DST and other markers of HPA axis function. PMID- 2929785 TI - Efficacy of psychoanalysis and psychoanalytically oriented psychotherapy. PMID- 2929786 TI - Citation for position of Alcoholics Anonymous on psychotropic medications. PMID- 2929788 TI - Olfactory stimuli as context cues in human memory. AB - Olfactory stimuli were used as context cues in a recognition memory paradigm. Male college students were exposed to 50 slides of the faces of college females while in the presence of a pleasant or an unpleasant odor. During the acquisition phase, ratings of physical attractiveness of the slides were collected. After a 48-hr delay, a recognition test was given using the original 50 slides and 50 new slides. The recognition test was conducted with either the original odor or the alternative odor present. A no-odor control group did not receive olfactory cues. The attractiveness ratings indicated that the odor variations had no effect on these social judgments. Analyses of d' scores, hits, and false alarms for the recognition performance indicated support for the predicted interaction in which presence of the same odor at both sessions led to better overall performance. PMID- 2929787 TI - How is a trumpet known? The "basic object level" concept and perception of musical instruments. AB - What are the object properties that serve as a basis for the musical instrument classification system, and how do general and specific experience affect knowledge of these properties? In the first study, the multimodal quality of properties underlying children's and adults' perception was investigated. Subjects listened to solos and identified instruments producing the sounds. Even children who did not have experience with all the instruments correctly identified the family of instruments they were listening to. The hypothesis of the second study, that musical instrument families function as a "basic level" in the instrument taxonomy, was confirmed. Variation in the basic level with varying expertise was documented in the third study with musicians. In the fourth study, children and adults identified the source of sounds from unfamiliar objects, Chinese musical instruments. It is suggested that the concept of affordances may be relevant for understanding the importance for behavior of different levels of abstraction of category systems. PMID- 2929789 TI - Opacity versus counterprojection: an analytic intervention explored. AB - A peculiarly effective intervention by the author's psychoanalyst is explored and discussed in terms of its implicitly expressive properties. It is placed in the context of the classical concept of opacity and more flexible Sullivanian ideas, as expanded and clarified by Havens. PMID- 2929790 TI - Iatrogenic factors in "managed" psychotherapy. AB - The clinical implications of the "case-manager" system are explored through a detailed case presentation. It is demonstrated that the introduction of a third person into the therapeutic relationship compromises the therapeutic alliance and the transference. Under such conditions psychotherapy is impossible. PMID- 2929792 TI - AIDS and confidentiality: legal concept and its application in psychotherapy. AB - Persons with positive HIV appear to have the same right to confidentiality as other medical psychiatric patients. The ethical and legal duties of practitioners who learn that their HIV positive patients are endangering others is discussed. The essential policies of the CDC, AMA, and APA are reviewed along with the current legal situation. One conclusion reached is that applying the Tarasoff doctrine to warn/protect a third party, if that party may already be infected, is useful only when the third party is moral and sensible enough to cease behavior that would spread the disease to others. PMID- 2929791 TI - Paleodigms and paleodigmatics: a new theoretical construct applicable to Munchausen's syndrome by proxy, child-abuse dwarfism, paraphilias, anorexia nervosa, and other syndromes. AB - A paleodigm is a formulation of ancient folk wisdom that encodes a causal explanation in a saying or story that penetrates the idiom of everyday language and influences behavior. Although paleodigms are not, per se, causative, they have diagnostic, prognostic, and therapeutic significance in syndromes like Munchausen's syndrome by proxy. PMID- 2929793 TI - Ethics in the practice of psychotherapy: a survey. AB - One hundred and one psychotherapists responded to a survey designed to obtain data concerning beliefs about various ethical issues encountered in psychotherapy. Opinions about ethical standards in many areas were quite varied for the entire sample. Differences also emerged when therapists were compared in terms of orientation and years of experience. PMID- 2929794 TI - Termination criteria in psychotherapy: a comparison of private and public practice. AB - Results obtained from a questionnaire regarding termination criteria in psychotherapy, revealed significant differences between the public and private sector. Additional differences were also found for: length of sessions, frequency of sessions, length of treatment, hospitalizations, medication usage, ethnicity, diagnosis, degree of perceived improvement, and degree of clinical improvement. PMID- 2929795 TI - Reframing to deal with patient resistance: practical application. AB - Patient resistance presents many therapeutic challenges. Reframing has proven to be a potent method of circumventing such issues. The present article describes methods of constructing, cultivating, and delivering reframes. Several examples of this intervention strategy are provided. PMID- 2929796 TI - Assassination of Indira Gandhi: impact on psychiatric patients. AB - The psychological impact of the assassination of Prime Minister Indira Gandhi on psychiatric inpatients was studied. A semistructured interview indicated faulty perception of, and inappropriate reaction to, the event and its implications in the patients, often colored by their background and illness. The Modified Brief Psychiatric Rating Scale indicated a significant rise in their psychopathology soon after the event. PMID- 2929797 TI - "Koro" (genital retraction syndrome): psychotherapeutic interventions. AB - "Koro" is a belief or delusion of retraction of the penis into the abdomen. Originally thought to be a Chinese and Indonesian culture-bound syndrome, it has recently been noted to occur in "Western" patients. Two Western patients with this syndrome are described and their psychotherapeutic treatment and outcome outlined. A stepwise approach to the treatment of the Koro symptom is suggested. PMID- 2929798 TI - The development of female transsexualism. AB - Characteristics by which to classify a woman as authentically transsexual are offered from earlier investigations and supplemented by findings from recent work with this type of patient. Developmental issues are discussed and six psychodynamic accompaniments listed. A case demonstrates how to identify the true female transsexual and how to understand her psychological processes. PMID- 2929799 TI - Assessing quality of care: another step forward. PMID- 2929800 TI - Public health and the new national effort. PMID- 2929801 TI - Health effects of the war in two rural communities in Nicaragua. Nicaragua Health Study Collaborative at Harvard, CIES, and UNAN. AB - We report on a pilot study to assess the effects of low intensity war in Nicaragua on the health of the civilian population. The study compared data from two regions in Nicaragua, one in an area of intense conflict, the other further removed from the war's violence. Information was obtained from a questionnaire administered to female heads of randomly selected households; structured interviews with community leaders and health workers; group discussions with community residents; and a review of regional and municipal death records. Height and mid-upper arm circumference of children were measured, and immunization records reviewed. The war has had a serious negative effect on the lives of the civilian population in both the war zone and the non-war zone, with the effects most severe in the war zone. In both communities, over half of the respondents reported the death of a friend or relative. In the war zone community, over one fourth of respondents reported attacks on family members in non-combat situations around their homes. Death by firearms was the leading cause of death in persons over age 6 in the war zone. Vaccination coverage, nutritional indices, and familial disruption were worse in the war zone community. The findings suggest that continued funding of the Nicaraguan contra forces by the United States may be harming the ostensible beneficiaries of that policy, and that use of such low intensity conflict as a foreign policy tool should be questioned. PMID- 2929802 TI - Beliefs about AIDS as determinants of preventive practices and of support for coercive measures. AB - We performed a telephone survey to explore relations between knowledge, beliefs (as defined in the Health Belief Model) and reported AIDS-preventive practices in a sample of 1,072 persons ages 18-65, living in the Montreal health region. AIDS preventive practices were more frequent among the young or single, and among those with one of four health beliefs: perceiving oneself as particularly susceptible to AIDS, perceiving the disease as particularly severe, perceiving it as particularly amenable to prevention, and having a strong general health motivation. Support for coercive measures to control the AIDS epidemic was widespread but was stronger among the less educated, married people, and those with a high level of one of the following beliefs about AIDS: perceived severity, susceptibility, curability, or barriers to treatment. AIDS-preventive practices and support for coercion under epidemic conditions share their most important modifiable determinants: perceived severity of AIDS and perceived susceptibility to it. This finding suggests that emphasizing them, as is done so often in public educational campaigns about AIDS, may indeed promote preventive practices, but may also unwittingly increase support for coercive measures toward people with the disease or at high risk of it. PMID- 2929804 TI - Outbreaks of hepatitis A among illicit drug users, Oklahoma, 1984-87. AB - Transmission of hepatitis A has been described in many settings, although few outbreaks have been reported among illicit drug users. We report six unrelated outbreaks of hepatitis A among users of marijuana and intravenously administered methamphetamine. Although the exact mode of transmission could not be determined, practices associated with illicit drug use may have facilitated transmission of hepatitis A. These outbreaks and other recent information indicate that illicit drug users may be at increased risk of acquiring hepatitis A infection. PMID- 2929803 TI - Preventing AIDS and other STDs through condom promotion: a patient education intervention. AB - We report on two studies that assessed the impact of a soap-opera style videotape on inner-city STD (sexually transmitted disease) patients' knowledge about and attitudes toward condom use, and willingness to redeem coupons for free condoms. Subjects in the first study who viewed the videotape (and participated in a brief oral recall session) had higher knowledge scores and more accepting attitudes than subjects who did not (knowledge test means of 11.1 versus 7.9, attitude index means of 13.0 versus 11.3). The intervention was most effective among those who were relatively poorly educated and, to a lesser extent, among those who reported less frequent use of condoms and fewer sex partners. In the second study, intervention group subjects were more likely than control group subjects to redeem coupons. Both groups exhibited a high level of interest in the free condoms. We argue that education and accessibility to free condoms can increase condom use and that health care providers have a vital role in promoting this form of STD prevention. PMID- 2929805 TI - New AIDS Prevention Research Center to be established at Columbia University. PMID- 2929806 TI - Race and the prevalence of syphilis seroreactivity in the United States population: a national sero-epidemiologic study. AB - We used the 1978 National Health and Nutrition Examination Survey to examine the prevalence of positive syphilis serologies in the US population. Analysis of risk markers--gender, age, marital status, education, income, and residence--indicates that all except gender are associated with syphilis seroreactivity, independent of race. Controlling for associated risk markers, the Black-White odds ratio of syphilis seroreactivity is 4.7 (95% CI = 2.7, 8.2). Current knowledge of racial differences in sexual and health care behavior does not explain the Black-White difference in the prevalence of syphilis seroreactivity. PMID- 2929807 TI - The role of secondary vaccine failures in measles outbreaks. AB - An outbreak of measles in 1985-86 in a community where measles vaccine trials had been carried out from 1974-76 allowed the assessment of the role of secondary vaccine failures in previously immunized children. A total of 188 children from the vaccine trial were followed. Of these, 175 seroconverted initially while 13 (6 per cent) required re-immunization (primary failure). A total of 13 cases of measles, eight of which were laboratory and/or physician-confirmed, were reported in this cohort. Of these, nine cases occurred in the 175 subjects who had hemagglutination inhibition test (HI) and neutralizing antibody responses following the initial immunization. These nine cases represent secondary vaccine failures. An additional four cases occurred in the 13 subjects with primary vaccine failure. We conclude that secondary vaccine failures occur and that while primary failures account for most cases, secondary vaccine failures contribute to the occurrence of measles cases in an epidemic. A booster dose of measles vaccine may be necessary to reduce susceptibility to a sufficiently low level to allow the goal of measles elimination to be achieved. PMID- 2929808 TI - Illness associated with child day care: a study of incidence and cost. AB - We studied 843 children under 36 months of age enrolled in a prepaid health plan from September 1985 through March 1986, to identify characteristics of day care which might be risk factors for infection and to describe the resulting economic costs. Children cared for in their own home had a mean of 2.03 infections diagnosed during the study period. Adjusted rates of excess infection (95 per cent CI) for children cared for in other settings were: -.09 (-.73, .54) in relatives' homes; .10 (-.51, .71) in day care homes; .79 (.13, 1.45) in day care centers; .60 (-.24, 1.46) in mother's day out programs; and .66 (-.01, 1.34) in multiple settings. Children in day care centers were 4.5 times more likely to be hospitalized than those in other settings (95 per cent CI = 1.55, 13.00), primarily due to an increased rate of tympanostomy tube placement (relative risk 3.79, 95 per cent CI = 1.04, 13.36). The strongest predictor of illness risk was the number of other children in the room. The mean monthly cost of medical care was $32.94 for children in the highest risk settings compared with $19.78 for those in other settings. Illness in a child in our study accounted for 40 per cent of parental absenteeism from work; the mean number of days lost per month was 0.52 for parents of children in day care centers compared with 0.37 for those of children in other forms of full time care outside the home. PMID- 2929809 TI - Recurrent outbreaks of giardiasis in a child day care center, Wisconsin. AB - In the 19-month period September 1983-March 1985, three outbreaks of giardiasis occurred in one large child day care center. Control measures instituted during each outbreak included case finding; pharmacologic treatment and follow-up testing of stool specimens for cases of giardia infection in day care children and staff, and their household contacts; facilitating and stressing personal and environmental hygiene, including altering diapering practices and teaching appropriate hand washing techniques. In the first, second, and third outbreaks, overall attack rates (stool analysis positive for Giardia lamblia) were determined for those persons with greater than or equal to 2 stool specimens submitted; attack rates in children were 47, 17, and 37 per cent, respectively; for tested staff, the rates were 35, 13, and 9 per cent; and for tested household contacts were 18, 9, and 5 per cent. Attack rates were highest for ambulatory diapered children, children attending the day care center greater than or equal to 40 hours per week, and children who were infected with G. lamblia in the most recent previous outbreak. Despite extensive efforts to identify cases, a cure rate of greater than 90 per cent in treated cases, and improvements in personal and environmental hygiene practices, G. lamblia infections recurred in outbreak proportions. PMID- 2929810 TI - The provision of services to persons with mental retardation and subsequent infection with human immunodeficiency virus (HIV). AB - We present the first reported cases of individuals with mental retardation who have subsequently become infected with human immunodeficiency virus (HIV). The implications of this finding for agencies which provide services to persons with mental retardation are described. Where conflicts arise, the authors propose that ethical review committees provide consultation to service agencies who must ultimately determine how they will provide for the needs of their clients. PMID- 2929811 TI - A new epidemiologic and laboratory classification system for paralytic poliomyelitis cases. AB - An epidemiologic classification of paralytic poliomyelitis cases (ECPPC) has been in use in the United States since 1976. In 1985, this classification system was reviewed because of recent changes in the epidemiology of paralytic poliomyelitis and improved laboratory capability to definitively characterize poliovirus strains. An alternative classification system was devised, the epidemiologic and laboratory classification of paralytic polio cases (ELCPPC), that incorporated virus isolation and strain characterization with epidemiologic information. Reported paralytic poliomyelitis cases for 1980-86 were classified by both the ECPPC and the ELCPPC classification systems. The new ELCPPC system classified 91 per cent of the reported cases as vaccine-associated, while the ECPPC system classified only 71 per cent of the reported cases as vaccine-associated. The proposed classification system provides more specific and useful information particularly concerning vaccine-associated paralytic poliomyelitis. PMID- 2929812 TI - The relationship between women's attitudes about condoms and their use: implications for condom promotion programs. AB - A survey of 759 women attending contraceptive care clinics revealed that a majority of women endorsed condom use as an important way to reduce the spread of AIDS (acquired immunodeficiency syndrome); 82 per cent reported past use of condoms, but only 14 per cent reported using condoms in addition to another form of contraception to prevent infection with sexually transmitted pathogens, including HIV (human immunodeficiency virus). Acceptance of condom advertisement, perceived male and peer acceptance of condoms, and the effect of condom use on the enjoyment of sexual intercourse predicted condom use. PMID- 2929813 TI - Sexual behavior changes and HIV antibody in a cohort of New York City gay men. AB - A sample of 357 gay/bisexual men, ages 20 to 65, were interviewed in 1985 regarding their sexual patterns over the course of the AIDS (acquired immunodeficiency syndrome) epidemic. Within four months after the interview, men were tested for antibody to HIV (human immunodeficiency virus) and 36 per cent were found positive. Cessation of receptive anal intercourse was associated with HIV negative antibody status, (OR greater than 3.0). Reducing the number of sexual partners, becoming monogamous, or eliminating other forms of sexual contact were not related to risk of HIV. PMID- 2929814 TI - A comparison of acquired immunodeficiency syndrome and Kaposi's sarcoma incidence rates, Atlanta, 1983-86. AB - Recent temporal trends in incidence rates for acquired immunodeficiency syndrome (AIDS) and Kaposi's sarcoma were compared in metropolitan Atlanta, Georgia. From 1983 through 1986 the age-adjusted incidence rate of Kaposi's sarcoma among White males ages 25-49 increased 11-fold (2.2-24.4/100,000 person years). The annual incidence rate of AIDS increased ten-fold (11.3-113.3/100,000). These findings do not support earlier reports that the proportion of AIDS patients with Kaposi's sarcoma has decreased over time. PMID- 2929816 TI - Tuberculosis surveillance in a state prison system. AB - After four inmates at two New Mexico prisons converted their tuberculosis skin tests, a mass screening program was carried out at all the State's adult correctional facilities (2,240 inmates). Previously unknown converters were found with a disproportionally high per cent of converters (6.8 per cent and 6.3 per cent) and reactors (14.4 per cent and 12.2 per cent) at the first two prisons. No index cases were found. State policy has been revised to include two-stage skin testing of new inmates, annual testing thereafter, and screening of all new correctional staff. PMID- 2929815 TI - The Hawaii Chlamydia Network Project: a successful program incorporating close intra-agency cooperation. AB - The Hawaii State Department of Health's Chlamydia Network Project screened 272 asymptomatic females for chlamydia; 20 (7.4 per cent) were found to be positive. When interviewed, 75 per cent (15/20) of the cases gave information such that their sexual partner(s) could be located. Ninety per cent (14/16) of the locatable partners were brought to examination within seven days. Keys to success were the training of family planning clinic staff in STD (sexually transmitted disease) control methods, and close intra-agency cooperation. PMID- 2929817 TI - Immunization coverage and social differentiation in urban Senegal. AB - We studied sociocultural factors associated with immunization coverage among a random sample of 500 mothers in the underprivileged suburbs of Dakar, Senegal. Factors associated with immunization of children under age 5 were maternal educational level and socioeconomic conditions (especially husband's regular salary); maternal age on arrival in town was more influential than total number of resident years in town; no effect of ethnicity was evident. PMID- 2929818 TI - Prevalence of diabetes in a Navajo Indian community. AB - The age- and sex-adjusted prevalence of non-insulin-dependent diabetes mellitus (NIDDM) of 494 (76 per cent) Navajo adults living in a reservation community was 10.2 per cent, approximately 60 per cent greater than the estimated prevalence (6.4 per cent) in the general US population. The screening protocol utilized likely underestimates the prevalence of NIDDM in this population. A high proportion of Navajo people were overweight when compared to the general US population. PMID- 2929819 TI - Uncompensated emergency care in hospital markets in Los Angeles County. AB - A survey of hospital emergency rooms in Los Angeles County was conducted in March 1987. Analysis of the distribution of uninsured emergency care patients revealed that private hospitals play a significant frontline role in terms of entry into the hospital system for patients who are unable to pay--almost one-half of such patients were treated in the emergency rooms of private hospitals. Hospitals serving markets in which a higher proportion of residents had incomes below the poverty level provided a greater share of uncompensated emergency room services. PMID- 2929821 TI - Professional midwifery. PMID- 2929820 TI - Television viewing and obesity in adult males. AB - We estimated the extent to which time spent watching television is associated with obesity and super-obesity among 6,138 employed adult males. After adjustment for age, smoking status, length of work week, measured physical fitness, and reported weekly hours of exercise, people who viewed TV more than three hours/day were twice as likely to be obese as those who viewed less than 1 hour/day. Those who viewed for 1 to 2 hours daily had a relative risk of 1.60 (1.21, 2.11). Physical fitness consistently confounded the associations between TV viewing and obesity/super-obesity, but the other control variables did not do so. PMID- 2929822 TI - Opportunities for lay midwifery practice. PMID- 2929823 TI - Smokeless tobacco: less seen at 1988 World Series. PMID- 2929824 TI - Community screening for HIV infection in Finland. PMID- 2929826 TI - Extraarticular reconstruction of the anterior cruciate ligament insufficient knee. A long-term analysis of the Ellison procedure. AB - This paper reports an analysis for treatment of anterolateral rotatory instability by the Ellison procedure, a technique involving rerouting a portion of the iliotibial band posterior to the fibular collateral ligament. A detailed description of the operative procedure is presented. One hundred four patients were evaluated for subjective improvement. The average length of followup was 51 months (range, 24 to 100 months). Eighty-one patients (80%) had a good or excellent result, 15 patients (14%) were rated fair, and 6 patients (6%) were rated poor. Sixty-three patients returned for a detailed clinical examination (average followup was 53 months; range, 24 to 100 months). An excellent or good objective rating was achieved in 49 patients (78%). Ten patients (16%) were rated as fair, and four patients (6%) were rated as failures. We recommend the Ellison procedure for the recreational athlete as a safe and effective mode of treatment for anterolateral rotatory instability. PMID- 2929825 TI - Proprioception in the anterior cruciate deficient knee. AB - Proprioception was quantified in a group of patients who had documented complete ACL tears. Threshold to detection of passive change in position of the knee was measured using a well-described test. Eleven patients with arthroscopically proven complete ACL tears and findings consistent with moderate to severe anterolateral rotatory instability were tested. Testing was done within the 30 degrees to 40 degrees range of knee flexion. Patients were blindfolded and the injured and uninjured knees were tested in random sequence so that the normal knee could serve as an internal control. Testing was also done in a blind manner, i.e., the examiner did not know which knee had been injured. An age-matched control group underwent identical testing. Potentially significant variables such as age, time from injury, and degree of rehabilitation as measured by thigh circumference and isokinetic testing of the knee were included in a multivariate analysis. Control subjects demonstrated virtually identical threshold values between their two knees, the mean variation being less than 2%. The test group, however, showed a significantly higher mean threshold value for the injured versus the noninjured knee (P less than 0.01), the mean variation being over 25%. Multivariate analysis demonstrated that changes recorded in the proprioception of the injured knee were attributable to the loss of the ACL rather than to other variables. Patients who have complete ACL tears and moderate to severe rotatory instability may also experience a decline in proprioceptive function of their knee. PMID- 2929827 TI - A stabilometric technique for evaluation of lower limb instabilities. AB - Stabilometry is a technique designed to register postural equilibrium control. This investigation used a computerized strain gauge force plate to measure sway movements in the frontal plane with the patient standing on one leg. Fifty-five young healthy individuals were studied as a reference group and to determine the reproducibility of the method. The clinical population consisted of 14 patients with unilateral injuries to the lateral ligaments of the ankle. These were measured, both with and without an ankle brace. The different parameters used to describe the body sway could well discriminate between the injured and the uninjured leg. When the brace was used the effect was obvious and none of the parameters showed any significant difference compared to the uninjured leg. PMID- 2929828 TI - The effect of tourniquet pressure on muscle function. AB - The adverse effects of excessive tourniquet pressure on underlying muscle were studied using a cat model. A direct effect of the magnitude of tourniquet pressure on the degree of muscle disability was observed. The effect of direct pressure on the muscle may contribute to the postoperative weakness seen in the quadriceps muscle. Our data, in conjunction with the results of other studies that correlate certain tourniquet times and pressures with potential adverse effects, suggest that the selection of an appropriate tourniquet pressure and duration will minimize the development of clinically significant complications. PMID- 2929829 TI - Isolated infraspinatus atrophy. A common cause of posterior shoulder pain and weakness in throwing athletes? PMID- 2929830 TI - Natural history of a type III fracture of the intercondylar eminence of the tibia in an adult. A case report. PMID- 2929831 TI - A biomechanical analysis of anterior cruciate ligament reconstruction with patellar tendon--a two year followup. PMID- 2929832 TI - Tibial collateral ligament bursitis. PMID- 2929833 TI - Operative ankle arthroscopy. Long-term followup. AB - Ankle arthroscopy has become an accepted procedure for the treatment of various intraarticular disorders. More than 100 ankle arthroscopies have been performed at our institution since 1983. To better define the role of arthroscopic surgery in the treatment of ankle disorders, we evaluated the preoperative examination and indications, operative data, and radiographs of those patients with a minimum of 1 year of followup. Fifty-eight ankles in 57 patients were identified; their average follow-up period was 25 months (range, 12 to 49 months). Preoperative diagnoses were synovitis (26), transchondral defects of the talus (17), degenerative joint disease (8), and osteophytes or loose bodies (7). Subjective results were good or excellent in 64% of cases. The best overall results were achieved in patients with synovitis (77%) and transchondral defects of the talus (71%). Degenerative joint disease patients did not do well. They had only 12% good or excellent results and a 43% rate of subsequent fusion. Complications included superficial and deep infections, temporary and permanent paresthesias, and hemarthroses; the overall complication rate was 15%. In conclusion, operative ankle arthroscopy can be useful in selected patients. It is an effective surgical procedure in patients with synovitis and transchondral defects of the talus. The benefits and long-term results are less predictable with loose bodies and impinging osteophytes; the results are poor with degenerative joint disease. There appears to be a significant risk of complication with ankle arthroscopy; however, with proper indications, a thorough knowledge of anatomical landmarks, and meticulous technique, good results can be obtained. PMID- 2929834 TI - Isokinetic muscular performance of the quadriceps in elite ice hockey players. AB - On four occasions during a period of 17 months, isokinetic maximum knee extensor output (peak torque and contractional work) and input (integrated electromyographic activity) during single and repetitive contractions were measured in 10 male elite ice hockey players. The tests were performed in the middle and at the end of the competitive season, and after two office training periods involving different types of training. No significant changes in peak torque at single maximum contractions occurred for the whole group of players during the investigation. Nor did the slope of decline in contractional work or the plateau level of the ratio of contractional work:integrated electromyographic activity during repetitive contractions change significantly. The most obvious finding was great interindividual differences in muscular performance. Intraindividually, changes in both peak torque as well as in slope of decline in contractional work and in plateau level of the ratio of contractional work:integrated electromyographic activity occurred during the different training periods. We conclude that local muscle adaptations, measured by isokinetic procedures, occur in the quadriceps as a result of ordinary training and games in elite ice hockey players. Because of the great interindividual differences in muscular performance and the different responses to similar training, we suggest individual programs for leg muscle training in ice hockey players. PMID- 2929835 TI - Dynamic EMG analysis of anterior cruciate deficient legs with and without bracing during cutting. AB - The purpose of this research was to determine if bracing altered muscle firing amplitude, duration, or timing, creating improved dynamic stability. We hypothesized that a derotational knee brace improved the stability of an ACL deficient knee by augmenting limb proprioception, causing hamstring muscles to increase in activity and/or to contract earlier during a side-step cut. Ten subjects with documented unilateral isolated ACL deficient knees and five normal controls participated. A strap dominant brace (Lenox Hill, Lenox Hill Brace, Inc., Long Island City, NY) and a shell dominant brace (CTi, Innovation Sports, Irvine, CA) were selected for study. Using footswitches and dynamic EMG, we tested each subject during performance of a side-step cutting maneuver. Subjects completed 15 trials: 5 without bracing, 5 with the strap dominant brace, and 5 with the shell dominant brace. Normals cut 10 times each on their dominant limb. In swing phase, subjects had 38% more and 32% higher lateral hamstring EMG activity than normals; in stance phase, subjects had less quadriceps and gastrocnemius activity but more medial hamstring activity. When braced during stance phase, the ACL deficient legs demonstrated a further reduction of 18% in quadriceps total activity and 14% in peak activity compared to the unbraced situation. The hamstrings showed a concomitant decrease of 18% in total activity. No timing differences were noted between the braced and unbraced conditions during swing or stance phase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2929836 TI - Tibiofemoral joint forces during isokinetic knee extension. AB - Using a Cybex II, eight healthy male subjects performed isokinetic knee extensions at two different speeds (30 and 180 deg/sec) and two different positions of the resistance pad (proximal and distal). A sagittal plane, biomechanical model was used for calculating the magnitude of the tibiofemoral joint compressive and shear forces. The magnitude of isokinetic knee extending moments was found to be significantly lower with the resistance pad placed proximally on the leg instead of distally. The tibiofemoral compressive force was of the same magnitude as the patellar tendon force, with a maximum of 6300 N or close to 9 times body weight (BW). The tibiofemoral shear force changed direction from being negative (tibia tends to move posteriorly in relation to femur) to a positive magnitude of about 700 N or close to 1 BW, indicating that high forces arise in the ACL when the knee is extended more than 60 degrees. The anteriorly directed shear force was lowered considerably by locating the resistance pad to a proximal position on the leg. This model may be used when it is desirable to control stress on the ACL, e.g., in the rehabilitative period after ACL repairs or reconstructions. PMID- 2929837 TI - Early experience with the GORE-TEX polytetrafluoroethylene anterior cruciate ligament prosthesis. AB - A prospective study of 41 patients with acute and chronic ACL deficiency underwent reconstruction with the GORE-TEX polytetrafluoroethylene (PTFE) ACL prosthesis beginning in November 1983. Thirty-nine patients who were at least 2 years from their surgical procedure were available for follow-up evaluation, which included subjective questionnaire, clinical examination, and instrumented ligamentous laxity tests. Eight patients had an acute injury to the ACL and 31 patients had chronic ACL insufficiency for which reconstruction was performed. Thirty-four patients had satisfactory results, allowing full return to activity with no appreciable symptomatology. Of the remaining five patients, four had a complete rupture of the prosthesis. The average knee arthrometric measurement improved from a 5.4 mm left/right difference preoperatively to a 2.0 mm left/right difference at 2 year followup. Nine patients had postoperative complications of one or more atraumatic episodes of a sterile effusion. Six patients had recurrent effusions; in five, arthroscopy revealed partial tears of less than one-third of the prosthesis. Three patients who had recurrent effusions had PTFE particles in their synovial biopsies. One patient had an immediate postoperative infection and to data has had salvage of the prosthesis and currently has a stable knee with full return to activities. Based on the early results of this study, the GORE-TEX PTFE ACL prosthesis provided a satisfactory method of reconstruction for ACL deficient knees. Based on the evaluation used, 87% of the patients had satisfactory results. Problems associated with use of this prosthesis include partial or complete tears of the prosthesis and sterile effusions, possibly due to synovial irritation from the PTFE particles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2929838 TI - Acute repair of the anterior cruciate ligament with lateral capsular augmentation. AB - Forty-seven patients had primary repair and extraarticular augmentation with a lateral loop of the iliotibial tract for acute rupture of the ACL. (All of these patients had anterolateral rotatory instability (ALRI) preoperatively as diagnosed by a positive jerk test.) Of these 47 patients, 36 were available for follow-up evaluation. Followup ranged from 6 to 68 months (average, 21.6 months). Twenty-three of the patients (64%) were rated as excellent or good. Ten of the patients (27.8%) were rated as fair, and three patients (8%) were rated as poor. Thirty-three of the 36 patients (91%) were objectively free of ALRI as tested by the jerk test and had 1+ or less result in a Lachman test, with a firm end point. Only one patient felt his knee to be unstable (he had a positive pivot jerk). More than 90% of the patients returned to sport, and 72% returned at their preinjury level. PMID- 2929839 TI - Sliding fibular graft repair for chronic dislocation of the peroneal tendons. AB - Chronic recurrent subluxation of the peroneal tendons can be a disabling condition in the young athlete. Conservative techniques of management, including taping, pads, or special shoes, are usually ineffective. Many authors have reported favorable results with surgical reconstruction. These repairs fall into four categories: periosteal reattachment, groove deepening, tenoplasty procedures, and bone block procedures. We are reporting the results of treatment of 12 patients with a sliding fibular graft procedure that has not previously been reported in the literature. Results were excellent in 11 of the 12 procedures. One patient with bilateral repairs reported recurrence of symptoms on one side and required reexploration. PMID- 2929841 TI - Articular mobility in ballet dancers. A follow-up study after four years. AB - A follow-up study of ballet dancers was conducted to determine the influence of 4 years additional training on articular mobility using Beighton's method. The score increased in 25 (45.5%) of the 55 dancers reexamined. Acquired forward flexion accounted for this increase in 21 (84%) of the 25 dancers. These 21 dancers had had significantly less training than had the 30 dancers who could forward flex when examined initially (P less than 0.0001), showing that forward flexion is acquired through training. There were significantly more hypermobile individuals among dancers who had continued dancing than among those who had stopped (P less than 0.03). However, only 2 (16.7%) of 12 dancers who had progressed in their careers were hypermobile. We conclude that 1) most ballet dancers are able to forward flex, 2) forward flexion is usually acquired and develops after 4 or more years of training, 3) the mobility score may assist in predicting who will continue dancing, but that 4) there is no association between hypermobility and dancing excellence. PMID- 2929840 TI - Early osteophyte formation after chemically induced articular cartilage injury. AB - We examined the early changes that follow injection of sodium iodoacetate (IA) into the guinea pig knee joint, using Safranin-O (SO) to stain the proteoglycan (PG)-rich matrix and the incorporation of Na35 SO4 to determine which cells have maintained, lost, or developed the ability to synthesize significant amounts of PGs. Within 24 hours following injection of IA, articular chondrocytes exhibited a marked loss in ability to synthesize PGs; this inhibition was complete after 2 weeks. Focal loss of SO staining of the interterritorial matrix was noted after 24 hours, progressing to a complete loss of staining after 2 weeks. In sharp contrast to the degenerative changes in the habitually loaded articular cartilage, cells at the chondrosynovial junction began incorporating Na35 SO4 and producing a matrix that stained with SO as early as 72 hours following injection. With time, this resulted in the development of prominent osteophytic cartilage that involved bone remodeling beneath the overlying cartilaginous cap after 3 weeks. PMID- 2929842 TI - An analysis of fitness and time-motion characteristics of handball. AB - This study was conducted to determine some fitness parameters of two elite handball players, including the current world champion, and also to determine some of the time-motion characteristics of the game of hand-ball. The VO2 max values of the two players were found to be similar (53.1 and 55.2 ml/kg/min), while the world champion was substantially higher on the anaerobic power test and in peak ventilation scores. The results of heart rate monitoring of these players indicated that the mean game heart rate was dependent on several external factors, such as the skill level of each player, the fitness level of each player, the length of the rallies, and the player in control of the rally. The mean heart rate for the world champion was 149 beats per minute (bpm) during each game, while that for the other skilled player was 163.6 bpm, which represented 80% and 88% of maximum, respectively. The average length of each rally was 9 seconds, and the mean pause time (between rallies) was 10 seconds, producing a work-to-test ratio of approximately 1:1. The ball was found to be in play for an average of 47.3% of the total mean game time of 17 minutes. Each player was found to take approximately 350 strokes per match, with the world champion, and eventually the winner, taking a greater number of serves. Handball training should consist of interval training at an intensity of at least 80% of maximum heart rate, with a work-to-rest ratio of 1:1 and an emphasis on 10 second intervals. PMID- 2929844 TI - Measurement of upper extremity torque production and its relationship to throwing speed in the competitive athlete. AB - This study was conducted to establish whether or not a correlation exists between peak torque production of upper extremity (UE) musculature and throwing speed. Eleven professional baseball players were tested for upper extremity peak torque production using a Cybex II Isokinetic Dynamometer. Throwing speed was measured with a radar gun. Results of statistical analysis performed on the data indicate a correlation between shoulder adductors and throwing speed. PMID- 2929843 TI - Nonoperative treatment of grade II and III sprains of the lateral ligament compartment of the knee. AB - The purpose of the study was to learn the long-term results of nonoperatively treated sprains of the lateral compartment of the knee joint, generally known to be relatively rare injuries. A multidimensional follow-up analysis was performed on an average 8 years after the injury in 11 patients with Grade II sprains and in 12 patients with Grade III sprains, including four standardized knee scoring scales for subjective, objective, functional, and radiographic evaluation, as well as isokinetic and isometric strength evaluations. The result in Grade II sprains of the lateral ligament compartment (LAT) was generally good, although residual lateral laxity was common. In Grade III sprains, the results were much worse, with a high frequency of persisting severe or gross lateral laxity, insufficiency of the ACL, muscle weakness, and posttraumatic osteoarthritis of the injured knee. Grade II sprains of the LAT respond successfully to nonoperative treatment; in Grade III sprains, however, such treatment cannot be recommended as a method of choice. PMID- 2929845 TI - Fat pad adhesion to partially torn anterior cruciate ligament: a cause of knee locking. AB - Isolated damage to the ACL was found on arthroscopic examination of 51 patients who had symptomatic knees. There were 47 male and 4 female patients. The average age of the patients was 26.5 years, ranging from 13 to 43 years. Twenty-four of the patients had isolated partial tears of the ACL, and 27 had isolated complete tears. The purpose of this study was to examine the clinical patterns and arthroscopic findings in these two groups. On examination, 12 patients were found to have locked knees. An additional six patients gave a history of knee locking. All 18 of these patients were clinically suspected of having meniscal damage; however, only partial and complete ACL tears were found at arthroscopy. Of these 18 patients who had locking knees, 15 had a partial tear of the ACL and 3 had a complete tear. Locking was involved primarily in the group with partial ACL tears (15 of 24); only 3 of the 27 patients who had complete tears described locking. Of the 12 patients who had locked knees on examination, all were found to have fibrosis and adhesions of the fat pad and the synovium adjacent to the ACL stump. All 12 of these patients had a partial tear of the ACL. The fibrosis and adhesions were histologically documented in 10 of those 12 patients. The three patients who had partial ACL tears and histories of locking were not observed to have adhesions of synovium to the fat pad, but did have an entrapped remnant of ACL between the tibial plateau and femoral condyle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2929846 TI - Idiopathic entero-colic lymphocytic phlebitis. A cause of ischemic intestinal necrosis. AB - Histological examination of the surgical specimens of three patients presenting with intestinal ischemic necrosis disclosed extensive lesions of lymphocytic phlebitis associated with thrombosis of different ages. Arterioles and arteries were not affected. The lymphocytic infiltrate was composed of a mixture of T- and B-lymphocytes. None of the patients showed clinical or laboratory evidence of systemic vasculitis. Follow-up ranged between 4 months and 5 years. There has been no recurrence necessitating reoperation. The etiology of this clinicopathological entity has not been elucidated. PMID- 2929847 TI - Paneth cell adenoma of the stomach. AB - A case of Paneth cell adenoma of the stomach in a 75-year-old woman is reported. At histological examination, a tubular adenoma with low-grade (moderate) dysplasia was found. The dysplastic cells had distinct coarse cytoplasmic granules that stained red with eosin and PAS but were negative with alcian blue pH 2.5. The adenoma may have developed from paneth cells present in areas of preexisting intestinal metaplasia. PMID- 2929848 TI - An analysis of some factors determining the sporozoite rates, human blood indexes, and biting rates of members of the Anopheles punctulatus complex in Papua New Guinea. AB - The degree to which Anopheles punctulatus complex members feed on humans in different Papua New Guinea villages has a significant effect on sporozoite rates. Among villages, the human blood index (HBI) of the members of the complex varied with the average number of persons sharing a bednet. Although dogs are the preferred hosts by the 3 malaria vector species, the number of dogs did not significantly affect the HBI. The HBI was dependent upon the human-biting rate, implying increased avoidance of anophelines by people relative to other hosts at times of greater mosquito numbers. Human-biting rates and HBIs were also influenced by the distribution of alternative hosts relative to people. PMID- 2929849 TI - In vitro activity of antimalarial compounds on the exoerythrocytic stages of Plasmodium cynomolgi and P. knowlesi. AB - Primary cultures of Macaca mulatta hepatocytes infected with sporozoites of Plasmodium knowlesi, P. cynomolgi (Cambodian strain), and P. cynomolgi bastianellii were exposed in vitro to 7 antimalarial compounds. The number of exoerythrocytic schizonts present after 4-7 days of culture was used to assess the activity. With pyrimethamine, proguanil, cycloguanil, primaquine, and 2 of its analogues (WR242511 and WR238605), marked inhibition of schizont formation could be achieved at concentrations below those causing a cytotoxic effect on the host hepatocytes. Chloroquine had only minimal schizonticidal activity at a concentration that produced severe hepatocyte toxicity. This simian in vitro system provides a reliable model for screening antimalarial compounds and for investigating their effects on the hepatic stage of malaria parasites. PMID- 2929850 TI - Deciphering western blots of tapeworm antigens (Taenia solium, Echinococcus granulosus, and Taenia crassiceps) reacting with sera from neurocysticercosis and hydatid disease patients. AB - Complex antigen mixtures displayed in Western blots may be immediately and quantitatively categorized with respect to specificity and immunogenicity by immunoplotting. This involves plotting the frequency with which each antigen band reacts with a set of immune sera against the frequency of the same band when reacted with another set of immune sera. Immunoplotting has proven to be a powerful method of analyzing Western blots of reactions between vesicular fluids from the metacestodes of Taenia solium, E. granulosus, and T. crassiceps, and sera from human cases of neurocysticercosis and hydatid disease. Immunoplotting readily sorts out those antigens useful for discriminative immunodiagnosis from the multitude of bands in the sera of sick and healthy people. It aids in assessing the antigenic similarity between the human parasites and the murine parasite T. crassiceps, validating the latter as an alternative source of antigens for immunodiagnosis of cysticercosis and hydatid disease. PMID- 2929851 TI - Zoonotic Onchocerca in a Japanese child. AB - A female Onchocerca was found in histopathological sections of a nodule removed from the foot of a 2-year-old girl in southern Japan. As in previously reported cases in Switzerland, Crimea, Canada, and the USA, evident morphological features of the worm resembled those of Onchocerca gutturosa and O. cervicalis, which are known to exist in cervical ligaments of cattle and horses, respectively, in Japan and elsewhere. PMID- 2929852 TI - Epidemiology of human anisakiasis: incidence and sources in France. AB - A retrospective study on anisakiasis was carried out in France with 32 laboratories specializing in parasitology. During January 1985-September 1987, 21 cases of anisakiasis were diagnosed and confirmed by parasitological identification or serology. Various fish species were involved. Although anisakiasis is not a major public health problem, there is a need for regulation in the fish industry and for consumer information. PMID- 2929853 TI - Ivermectin for human strongyloidiasis and other intestinal helminths. AB - Since ivermectin, a mixture of 2 closely related macrocyclic lactones, has proven highly effective against animal intestinal nematodes, trials were undertaken to determine its efficacy against human intestinal nematodes. We tested 110 patients with strongyloidiasis and 90 with enterobiasis; many had other intercurrent intestinal nematode infections. Stool examinations were done before and after patients were given a single dose of oral ivermectin capsules (50, 100, 150, or 200 micrograms/kg body wt); 55 recipients of 100 or 200 micrograms/kg doses received a second identical dose the next day. Kato and saline smears, ethyl acetate concentration, modified Baermann's technique, and Harada-Mori cultures were repeated; cure was defined as complete absence of eggs and/or larvae from stools tested 30 days after dosing. Ivermectin was well tolerated. Overall cure rates at all doses 30 days after therapy averaged 88% for strongyloidiasis, 100% for ascariasis, 85% for trichuriasis, and 85% for enterobiasis. Ancylostoma duodenale and Necator americanus were little affected. PMID- 2929854 TI - Primary hepatic actinomycosis: a diagnostic problem. AB - A fatal case of hepatic actinomycosis in an immuno-compromised host is described. Diagnosis was delayed because of the rarity of this disease and because amoebic liver abscess, common in the tropics, has a similar presentation. PMID- 2929855 TI - Direct nephrotoxicity of Russell's viper venom demonstrated in the isolated perfused rat kidney. AB - Envenoming by Russell's Viper (Vipera russelli) is an important cause of acute renal failure. The mechanism of renal damage is unresolved. It is difficult to obtain evidence of a direct nephrotoxic action because of the coincidental disturbance to the systemic circulation. We studied the action of Russell's Viper venom on the function of the isolated perfused rat kidney. Direct nephrotoxic action was indicated by a dose dependent decrease in inulin clearance and an increase in fractional excretion of sodium seen at venom concentrations down to 50 ng/ml, a concentration likely to be achieved in the human circulation after envenoming. The isolated perfused kidney was also used to assess the efficiency of antivenom and for a comparison with snake venoms from the Thai cobra (Naja kauothia) and the Nigerian Saw-Scaled Viper (Echis ocellatus). PMID- 2929856 TI - Human depredation by vampire bats (Desmodus rotundus) following a hog cholera campaign. AB - Hog cholera control efforts in Belize in 1975 included the slaughter of village pigs, a primary food source for the vampire bat (Desmodus rotundus). The bats then fed on secondary food sources, including humans. In 1 village, 22% of the families interviewed were exposed to attacks: 17 children and 2 adults were bit. Human depredation was not continuous as Desmodus located other hosts. PMID- 2929857 TI - Lympho-cutaneous Kaposi's sarcoma in an African pediatric AIDS case. AB - A case of disseminated Kaposi's sarcoma with lymphoid and mucocutaneous involvement in an African infant with acquired immune deficiency syndrome is reported. The child died within 2 months after recognition. PMID- 2929858 TI - Neoplasms of the anus. PMID- 2929859 TI - The value of continuous 72-hour peritoneal lavage for peritonitis. AB - Studies were performed in 120 rabbits to determine whether 72-hour peritoneal lavage is beneficial or harmful in the treatment of peritonitis. Results showed that against a high concentration fecal inoculum (90 percent mortality), peritoneal lavage containing gentamicin and clindamycin reduced mortality to 10 to 20 percent (p less than 0.05). Parenteral antibiotics alone and lavage not containing antibiotics did not decrease mortality. By contrast, against a low fecal inoculum (30 percent mortality), peritoneal lavage containing gentamicin and clindamycin did not alter mortality. However, lavage not containing antibiotics increased mortality to 70 to 80 percent (p less than 0.05). These data demonstrate that continuous peritoneal lavage may be helpful in the treatment of peritonitis provided the lavage solution contains antibiotics and may be harmful if it does not contain antibiotics. PMID- 2929860 TI - Pitfalls in the management of penetrating chest trauma. AB - A prospective study designed specifically to analyze errors in management and iatrogenic complications was conducted on 234 consecutive patients with penetrating chest trauma. Eleven percent of penetrating pleural injuries were incorrectly diagnosed on initial physical and radiologic examination, but this led to wrong management decisions in only 4 percent. Decisions regarding intercostal tube drainage were particularly inaccurate when emergency intubation was required prior to chest radiography. Atypical clinical features of penetrating cardiac injuries caused delay in diagnosis and thoracotomy in 3 of 14 patients. Only two of four mediastinal vascular injuries were recognized on initial examination. Transdiaphragmatic injuries were initially missed in 5 of 14 patients. This resulted in management errors and delay in these patients. Awareness of atypical presentations and circumstances in which misjudgments and wrong decisions are prone to occur should help to avoid pitfalls and reduce mortality from penetrating chest trauma. PMID- 2929861 TI - Follow-up on flow cytometric DNA analysis of squamous cell carcinoma of the tongue. AB - Preliminary data from this institution suggested that flow cytometric DNA analysis was an objective prognostic indicator in archival localized squamous cell carcinoma of the tongue. Technical improvements were made, including analysis of tumor, normal tissue, and a combination of the two; standardized cursor placement; mathematic determination of tetraploid populations; and development of a statistical analysis. A larger number of patients (60) with this disease were reviewed. DNA content was related to disease-free survival, local recurrence, regional metastasis, and incidence of second primary tumors. There was no significant difference between aneuploid and diploid tumors with respect to the variables analyzed. We believe these technical improvements will enhance flow cytometric DNA analysis of paraffin-embedded tissues. However, in this retrospective review of localized squamous cell carcinoma of the tongue, DNA analysis was not a valuable prognostic indicator. Only prospective studies will address this issue. PMID- 2929862 TI - Treatment of pulmonary manifestations of gastroesophageal reflux in children two years of age or less. AB - Apnea and worsening bronchopulmonary dysplasia as well as recurrent aspiration pneumonia have been found to be consequences of gastroesophageal reflux in infants and young children. Antireflux procedures are effective in preventing gastroesophageal reflux; however, the effect of this operation on the course of these respiratory problems in very young patients is not known. We reviewed the results in 51 patients 2 years of age or less who underwent an antireflux fundoplication for pulmonary problems attributable to severe gastroesophageal reflux unresponsive to medical treatment. Twenty-eight patients had recurrent episodes of aspiration pneumonia, 14 had nonimproving or worsening bronchopulmonary dysplasia, and 9 had unexplained apneic episodes. Seventy-three percent of these patients had coexisting congenital anomalies or acquired problems. No operative deaths and no major surgical complications occurred. There were eight late deaths occurring between 1 and 25 months postoperatively: three were due to associated congenital anomalies or acquired problems, three to sepsis, and two to sudden infant death syndrome. Of the 43 surviving children, 91 percent with preoperative recurrent aspiration pneumonia had no additional episodes after Nissen procedure. Eighty-eight percent of the infants with unexplained apneic episodes showed marked benefit and 83 percent of those with bronchopulmonary dysplasia had clinical improvement. There were no late problems attributed to the operation even when it was performed in preterm infants. Therefore, we recommend fundoplication for patients 2 years of age or less who have a persistent pulmonary problem attributed to gastroesophageal reflux that does not respond to medical therapy. PMID- 2929863 TI - Lymphocyte function in obstructive jaundice. AB - Sepsis is a major factor in the high mortality and morbidity after surgery for obstructive jaundice. Several studies have suggested that reticuloendothelial function is depressed, but changes in lymphocyte function are poorly understood. A model of obstructive jaundice has been produced by chronic common bile duct ligation in eight dogs. In vitro lymphocyte studies were performed both at 2 and 3 weeks duration of jaundice and compared with simultaneous healthy control subjects. Icteric animals showed no abnormality of natural killer cell function. Relative numbers of T and B lymphocytes and their subsets were unchanged. T lymphocyte responses to three mitogens were not significantly reduced in jaundiced animals. Serum immunoglobulin levels were unchanged compared to those before surgery apart from a significant rise in immunoglobulin A. No evidence of circulating immunosuppressive factors was found by mitogen testing on normal lymphocytes in the presence of pooled serum from jaundiced animals, normal serum, or normal serum with added bilirubin. Our study does not suggest that impairment of lymphocyte function contributes significantly to the dangers of sepsis in obstructive jaundice. PMID- 2929865 TI - Results of vascular surgery in younger versus older patients. AB - We reviewed the results of reconstructive surgery at the aortoiliac and femoropopliteal levels in two age groups. Although patency rates were similar, when failure occurred, the amputation rate in the group under age 50 was almost three times that in the group over age 60. Practical application can be made in the preoperative preparation of the younger patient presenting with lower limb occlusive disease. More research of arteriosclerosis in the young is needed. PMID- 2929864 TI - Altered pharmacokinetics of antibiotics during vascular surgery. AB - Prophylactic antibiotics significantly decrease the incidence of infection in various surgical procedures. Although antibiotics must be administered preoperatively to be effective, it is unknown whether therapeutic concentrations are necessary throughout the operation to prevent infection. Furthermore, the pharmacokinetics of antibiotics during surgical procedures is not well understood. Several factors, including blood loss, fluid redistribution, and changes in renal blood flow may alter the pharmacokinetic disposition of the antibiotic. In a controlled investigation of intraoperative antibiotic pharmacokinetics, cefamandole was studied in eight patients undergoing elective surgery of the abdominal aorta and peripheral vasculature. Both elimination half life (67 +/- 19 minutes versus 93 +/- 23 minutes) and the volume of distribution (16.8 +/- 5.3 liters versus 25.2 +/- 11.9 liters) increased when compared with the preoperative state. The increased volume may be due, in part, to redistribution of fluid. Plasma concentrations of antibiotic were low at the time of graft placement in those patients with normal renal function. Additional antibiotic dosing may be warranted prior to prosthesis insertion in these patients. PMID- 2929866 TI - Perforated typhoid enteritis: operative experience with 108 cases. AB - A retrospective review of 108 consecutive patients with perforated typhoid enteritis managed operatively over a 4-year period at Baptist Medical Centre, Ogbomoso, Nigeria is presented. There were 75 males and 33 females with an average age of 19.7 years. Presenting symptoms were fever, abdominal pain, vomiting, and either diarrhea or constipation. One hundred patients (93 percent) underwent debridement of the perforation and two-layer bowel closure. Postoperative morbidity included intraabdominal abscess, wound dehiscence, and subsequent bowel perforation. Most of the 35 deaths (32 percent mortality) were attributed to overwhelming sepsis which progressed despite aggressive operative management and antibiotic administration. The key to improved survival in this deadly disease lies not in a better operation or improved perioperative care but in the prevention of typhoid fever by providing safe drinking water and improved sanitation methods for all of the global community. PMID- 2929867 TI - Results of urgent appendectomy for right lower quadrant tenderness. AB - The outcome was examined for 196 cases of urgent appendectomy in patients with abdominal pain and right lower quadrant tenderness and signs of peritoneal irritation. Appendicitis was found in 94 percent, and there was a 6 percent negative appendectomy rate. There were no complications among the patients with normal appendixes. Complications among cases of appendicitis compared favorably with other published series. PMID- 2929868 TI - Carotid endarterectomy for high plaques. AB - Seventeen instances of high plaque (plaque extending up to the level of the second cervical vertebra) were encountered out of a total of 454 carotid endarterectomies (3.7 percent). With careful dissection and knowledge of anatomy superior to hypoglossal nerve, carotid endarterectomy was accomplished without resorting to mandibular subluxation or dislocation. There was no operative mortality or perioperative strokes. One patient had perioperative myocardial infarction and another sustained temporary glossopharyngeal nerve dysfunction. High carotid plaques were more common in male patients with bilateral stenoses or contralateral internal carotid occlusion and could be suspected by findings of preoperative carotid arteriography in some instances. In the majority of cases, extension of high plaque in a tongue-shaped manner on the posterior wall of the internal carotid artery was an unexpected finding at the time of carotid endarterectomy. PMID- 2929869 TI - Axillary dissection: use of a mechanical retractor. AB - Operative axillary exposure can be conveniently maintained by means of a table based retractor which serves to displace the pectoral muscles medially. The shoulder is abducted and the arm hung from the horizontal cross bar of the device. By means of this method, complete axillary clearance can be accomplished with less assistance and improved visibility for the participants. PMID- 2929870 TI - The Roux-Y technic and syndrome. PMID- 2929871 TI - Correlation of otosclerotic foci and degenerative changes in the organ of Corti and spiral ganglion. AB - Statistical analyses of histopathologic findings in the cochlea and spiral ganglion of 37 temporal bones with otosclerosis, 12 controls of similar age, and seven controls with normal hearing were performed. In temporal bones with otosclerosis there was significant atrophy of the spiral ligament and stria vascularis in regions with endosteal involvement by otosclerosis, compared with regions without endosteal involvement (P less than .0001). There was more generalized atrophy of the stria vascularis in cochleae with two or more sites of endosteal involvement by otosclerosis than in cochleae with only one site of endosteal involvement (P less than .02), cochleae in temporal bones with otosclerosis but without endosteal involvement (P less than .05), or cochleae of controls of similar age (P less than .007). In addition, there was more atrophy of the spiral ligament in cochleae with two or more sites of endosteal involvement than in cochleae of similar age from the control group (P less than .03). In temporal bones with otosclerosis, there was no significant difference in counts of outer hair cells and density of spiral ganglion cells between regions demonstrating endosteal involvement by otosclerosis and regions without such involvement. However, total outer hair cell counts were lower in cochleae with two or more sites of endosteal involvement of otosclerosis than in cochleae with one site of endosteal involvement (P less than .04), cochleae in temporal bones with otosclerosis but without endosteal involvement (P less than .02), or cochleae from individuals of similar age but without otosclerosis (P = .05). Comparison of the mean bone conduction threshold, as measured in life, in temporal bones with otosclerosis compared with the air conduction threshold in aged-matched controls, demonstrated that only cochleae with two or more sites of endosteal involvement had a mild but statistically significant (P = .05) decrease in hearing. There was no evidence to support the concept that otosclerotic foci without stapedial fixation frequently cause significant degeneration of the cochlea or elevation of bone conduction thresholds. PMID- 2929872 TI - Quantitative evaluation of sensorineural structures following stapes surgery. AB - Sensorineural hearing loss may occur following stapes surgery. The reason for this remains unclear in spite of experimental studies in animals and postmortem temporal bone evaluations in humans. In this study, we quantitatively evaluated the sensorineural elements of six human temporal bones after stapes surgery. Outer hair cell loss in the upper basal turn was present in two cases. This lesion has not previously been described in human temporal bones after stapes surgery. In temporal bones with preoperative sensorineural hearing loss, evidence of presbycusis was also present. The importance of quantification in evaluating these structures must be stressed. PMID- 2929874 TI - The immunopathology of olfactory nerve injury and hemorrhage in gerbils. AB - Patients with head injury may experience olfactory dysfunction. Unfortunately, little is known about changes in the olfactory neuroepithelium caused by intracranial olfactory nerve injury and hemorrhage. We performed olfactory nerve section or bulbectomy in 53 Mongolian gerbils and subjected the olfactory neuroepithelium to immunohistochemical analysis. A decrease or disappearance of the antiserum to an olfactory marker protein containing olfactory receptor neurons was evident in the sectioned group. Degeneration of the olfactory neuroepithelium contralateral to olfactory nerve injury was also noted in animals with perineural hemorrhage. These findings suggest that olfactory dysfunction may occur not only with nerve injury but also secondary to intracranial hemorrhage. PMID- 2929873 TI - Real time multivariable laser Doppler analysis of arterial and venous compromise. AB - Laser Doppler perfusion monitoring was used to assess microcirculatory blood flow, volume, and velocity before and after total arterial or total venous occlusion in 18 buttock island flaps. Critical analysis of these three laser Doppler perfusion values was found to be useful in differentiating adequately perfused skin from inadequately perfused skin, as well as in distinguishing arterial from venous compromise. Multivariable laser Doppler analysis demonstrated that arterial occlusion produced a more rapid and greater percentage decrease in flow and volume values than did venous occlusion. Arterial occlusion produced an insignificant percentage change in velocity values, whereas venous occlusion produced a substantial percentage decrease in velocity values. The substantial intrasubject and intersubject variability in absolute laser Doppler perfusion values suggests that normalized or percentage change values are more revealing than absolute values, although they require the acquisition of reliable baseline data. PMID- 2929875 TI - Early reexploration of the parotid wound following parotidectomy. AB - Our experience with reexploration of the parotid wound following parotid gland surgery is presented. There is scant information in the literature to guide the head and neck surgeon in deciding when, and indeed whether, he can safely reexplore the parotid wound following parotidectomy for the removal of residual disease or for determination of neural integrity. The authors treated six patients at Stanford University (Stanford, CA), all of whom underwent reexploration of the parotid wound. Four patients were reexplored to remove residual disease, and two patients were reexplored to evaluate the integrity of the facial nerve after evidence of neural degeneration. Reexploration was undertaken from seven to 23 days after the primary surgical procedure. In all cases, no difficulty was encountered in identification and repair of the facial nerve or removal of residual disease. Five of these patients have fully recovered facial nerve function; one is awaiting recovery after a facial nerve grafting procedure. We recommend early reexploration of the parotid wound following parotidectomy for the removal of residual disease and to assess the integrity of the facial nerve in instances of neural degeneration. Reexploration may be easily and safely accomplished within 3 weeks of initial surgery without significant risk of further neural damage. PMID- 2929876 TI - The transformation of laryngeal keratosis into invasive carcinoma. AB - Although 93.0% to 97.0% of all laryngeal carcinomas are diagnosed on the first biopsy, 3.0% to 6.7% of them occur in patients who have what is initially diagnosed as "laryngeal keratosis." To study this phenomenon, we examined data from 1,019 patients with laryngeal keratosis seen between 1962 and 1981. Eleven patients with keratosis and initially undetected cancer at different laryngeal sites were excluded, as were 87 outside referrals for whom no records were available beyond the histologic report. The remaining 921 patients were classified on the basis of the initial histologic findings into groups comprising 604 patients with keratosis without atypia (group 1), 204 patients with mild atypia (group 2), 23 patients with moderate atypia (group 3), and 90 patients with severe atypia (group 4). All 921 were followed for from 5 to 25 years. Invasive carcinoma of the larynx developed in 18 patients from group 1 (3.0%), 15 from group 2 (7.4%), four from group 3 (17.4%), and 25 from group 4 (27.8%). Fifty-seven patients (91.9%) developed invasive carcinoma after less than 10 years but only five (8.1%) did so after 10 years or more. PMID- 2929877 TI - Free gastroomental flap for head and neck reconstruction: assessment in an animal model. AB - This study was performed to evaluate the free gastroomental flap for the reconstruction of mucosal and soft tissue defects after ablative surgery for head and neck cancer. Its use in a dog model was assessed in terms of the feasability of the surgical technique, acid secretion by the gastric mucosa, changes in the cell population of the graft, and the possibility that the omentum may augment lymphatic drainage after cervical node dissection. Gastroomental flaps were harvested, based on the gastroepiploic artery, and transplanted to the neck in ten dogs. Neck dissection and creation of a defect in the floor of the mouth were followed by microvascular anastamosis of the gastroepiploic vessels to suitable recipient vessels in the neck. Following this, the flap was sutured into place, reconstructing the defect in the floor of the mouth. The omentum was draped over the carotid artery and into the upper mediastinum. Intraoral pH remained stable during a 6-month follow-up period and there was no stomatitis noted. Radionuclide images suggested that the omental lymphatics contributed to regional lymphatic drainage. Histologic examination following sacrifice at 6 months showed atrophy of gastric glands but no epithelial metaplasia. We conclude that the free gastroomental flap is feasible, provides immediate restoration of soft tissue bulk, supplies a mucosal surface that adapts to the oral environment, and may augment regional lymphatic drainage. PMID- 2929878 TI - The surgical approach to the endolymphatic sac and the cochlear aqueduct in the guinea pig. AB - The endolymphatic sac and cochlear aqueduct are primary passages of the endolymphatic and perilymphatic fluid compartments in the labyrinth. Closure of the endolymphatic sac and duct in the guinea pig will result in the development of endolymphatic hydrops. Although obstruction of the cochlear aqueduct in this species does not seem to result in any dysfunction, this structure may serve in the dynamics of inner ear fluid physiology. The anatomy of the guinea pig temporal bone is described with special emphasis on the endolymphatic sac and cochlear aqueduct. Surgical techniques to gain access to these structures through both a middle and posterior cranial fossa approach are described. PMID- 2929879 TI - Free tissue transfer in head and neck reconstruction. AB - With continuing advances in microsurgery, the importance of free flap transfers in reconstruction has increased in every branch of surgery. Several free flaps (both simple and compound) will be described. The transfer of a bulk of tissue by microvascular tissue transfer is a reliable and proven method of reconstruction. The objective for microvascular surgery is to develop techniques of tissue transfer that restore function and improve appearance. There is no greater challenge than reconstructive surgery of the head and neck. PMID- 2929880 TI - Functional architecture of the nasopharyngeal tonsil. AB - The exact architecture of the normal nasopharyngeal tonsil remains obscure because most histopathologic investigations have been based on surgically removed adenoids. We compared enlarged adenoids and normal nasopharyngeal tonsils under both light and electron microscopes. The marked features of clinically enlarged adenoids were a large extension of the reticular epithelium and increased germinal centers. A tendency toward increased stratified squamous epithelium and decreased ciliated epithelium was apparent in enlarged adenoids, possibly due to inflammatory conditions. One type of nonciliated cell seemed to transport foreign material into underlying lymphocytes, as do the M cells of gut-associated lymphoid tissue. This type of nonciliated cell was rarely found in the extended reticular epithelium of enlarged adenoids. These findings suggest a disturbance of the antigen-trapping system and surface protections in adenoidal enlargement. PMID- 2929881 TI - Effects of middle ear effusion on neutrophil function. AB - The neutrophil chemotactic activity of middle ear effusions (MEE) was measured in patients with pediatric chronic, adult chronic, and acute otitis media with effusion (OME). Chemotactic activity differed significantly among the three groups of otitis media in the following order: adult chronic less than pediatric chronic less than acute. Culture-positive effusions had higher chemotactic activity than did those that tested culture negative, suggesting that bacterial infection is related to neutrophil chemotactic activity. The chemotactic function of normal peripheral neutrophils was not enhanced by preincubation with MEE, but their bactericidal function was enhanced. In conclusion, bacterial infection in the middle ear is one of the major determining factors of neutrophil infiltration during OME, and MEE enhances the bactericidal function of neutrophils. PMID- 2929882 TI - Specific immune response of the adenoids to a respiratory antigen. AB - The specific antibody response of the adenoids to a respiratory antigen was investigated, both in vitro and in vivo. The in vitro immunoglobulin (Ig) production of adenoidal and tonsillar lymphocytes in the same patient in 18 cases was measured by an enzyme-linked immunosorbent assay. Adenoidal lymphocytes produced more IgM than IgG or IgA under culture conditions without any mitogens, whereas IgG was the major Ig produced by tonsillar lymphocytes. The same results were obtained when cultured with pokeweed mitogen. Under culture conditions with Dermatophagoides farinae (mite) antigen, adenoidal lymphocytes produced only specific IgM class antibody, and at a level significantly greater than tonsillar lymphocytes. Through an in vivo study, we established experimental adenoidal tissue in the guinea pig by long-term exposure to an ovalbumin aerosol. Infiltration of cells producing the specific antibody against an ovalbumin was demonstrated in the epipharyngeal mucosa using immunofluorescent staining. Our results confirm that the adenoids play a role in specific immune responses to respiratory antigens. PMID- 2929883 TI - Respiratory disturbance during sleep due to adenoid-tonsillar hypertrophy. AB - The pathophysiologic results of respiratory disturbances caused by adenoid tonsillar hypertrophy are reported. In each case, we monitored intraesophageal pressure to accurately assess respiratory effort, and recorded a sleep diary to detect disorganized sleep habits and disturbed sleeping-waking rhythms. We noticed that great respiratory effort existed not only during light sleep, but was also continuously observed during deep sleep despite the total disappearance of obstructive apneas. Furthermore, upper airway obstruction caused by adenoid tonsillar hypertrophy and hypoxemia during sleep in the rapid eye movement stage were found to be closely related to the sudden infant death syndrome. A sleep diary recording sleep habits and regularity of night sleep seems to provide reliable indicators for the determination of surgical intervention. PMID- 2929884 TI - Chemosensitivity of squamous cell carcinoma grown in implantable chambers. AB - This study was motivated by the need to develop new methods to predict tumor response to chemotherapeutic agents. Using implantable cell-growth chambers, squamous carcinoma cells from head and neck tumors were xenografted into the peritoneal cavity of immunocompetent rats. Animals were divided into control and treatment groups. The treatment groups received intravenous cisplatin (CDDP) or 5 fluorouracil (5-FU) v normal saline solution for the control. Animals from each group were randomly selected and killed on days 3, 5, and 7 postimplantation. The chambers were retrieved, the media aspirated, and cells counted. Exponential growth curves were derived for the control and treatment groups. Statistically significant growth inhibition was observed for both treatment arms, compared with controls. This method of chemosensitivity testing proved to be inexpensive and reliable, and demonstrated tumor cell killing by 5-FU and CDDP. PMID- 2929885 TI - Plasma-mediated excimer laser ablation of bone: a potential microsurgical tool. AB - A pulsed ultraviolet excimer laser was used to ablate bone in vitro at 193, 248, 308, and 351 nm and in vivo at 193 nm. Ablation was dependent on sufficient fluence (energy delivered per unit area per pulse) for plasma formation at the target site at all wavelengths. Adjacent tissue damage at various fluences for each wavelength was examined using a light microscope. Damage was minimal at 193 nm (1 to 3 microns) and most extensive at 351 nm (60 to 75 microns). This is in sharp contrast to the 1 to 3 mm of adjacent thermal damage produced when carbon dioxide lasers are used to ablate bone. Differences in the degree and type of damage to adjacent tissues among the wavelengths studied indicated that other ablation mechanisms and tissue interactions are involved in addition to simple plasma vaporization of bone. Bleeding during and after ablation demonstrated that the use of this laser does not cause thermal damage, which would cauterize adjacent vessels. Pre- and post-mortem lesions made at identical power and pulse settings were of equal depth, indicating that bleeding does not affect the ablation rate. The excimer laser has potential as a microsurgical instrument for the precise removal of bone with minimal damage to adjacent structures. PMID- 2929887 TI - Classification systems for describing nursing practice. Working papers. PMID- 2929886 TI - Earn what you're worth: a nurse's guide to better compensation. PMID- 2929888 TI - Developments in nursing classification. Nursing diagnosis. PMID- 2929889 TI - Classifying human responses in psychiatric-mental health nursing. PMID- 2929890 TI - Developments in nursing classification. Interventions. PMID- 2929891 TI - Classification of outcome measures in nursing care. PMID- 2929892 TI - Historical perspective and ANA policies. PMID- 2929894 TI - Major classification systems in health care and their use. AB - The systems discussed above are the most commonly used, though a brief check with any medical records department will reveal many more available. Any nurse attempting to retrieve records for any purpose will have had to give instructions translatable into whatever system is in use in the institution. Anyone wishing to add to or replace a coding system in use will have to demonstrate both the need for and efficacy of the changes. PMID- 2929893 TI - Developments in nursing classification. Omaha system. PMID- 2929896 TI - An introduction to the science and art of taxonomy. PMID- 2929895 TI - The Nursing Minimum Data Set and its relationship to classifications for nursing practice. PMID- 2929897 TI - The clinical nurse specialist: a catalyst in the nursing diagnosis evolution. PMID- 2929898 TI - Challenge to the profession. PMID- 2929899 TI - Anaesthetists, lawyers and the public. PMID- 2929900 TI - Variables of patient-controlled analgesia. 2. Concurrent infusion. AB - The effectiveness of morphine after surgery by patient-controlled analgesia alone or with a concurrent infusion was studied. The infusion did not reduce the dose of self-administered analgesic and patients treated in this way received twice as much drug as those who used patient-controlled analgesia alone. Pain control was similar in both groups. The practice of patient-controlled analgesia plus infusion requires critical review. PMID- 2929901 TI - Intravenous regional anaesthesia of the arm. Effect of the technique of exsanguination on the quality of anaesthesia and prilocaine plasma concentrations. AB - The effects of different techniques of exsanguination of the upper arm during intravenous regional anaesthesia on prilocaine plasma concentrations, quality of anaesthesia, toxic symptoms after deflation of the tourniquet and injection pressure of the anaesthetic were studied in 10 healthy male volunteers. The nondominant arm was exsanguinated using either Esmarch's bandage or elevation of the arm for 2 minutes plus arterial occlusion by compression of the brachial artery. The injection pressure after the prilocaine dose (3 mg/kg) was significantly higher in the elevation group (maximally 98 mmHg). There were no statistically significant differences in the onset of, or recovery from, anaesthesia between the groups. Various mild toxic symptoms were experienced in the central nervous system after deflation of the tourniquet. However, there was no correlation between the two techniques and the degree of severity of the toxic symptoms. The highest single venous plasma concentration (total) of prilocaine was 2.3 micrograms/ml measured from the contralateral cubital vein (elevation group, 2 minutes). The differences in prilocaine concentrations between the groups were not statistically significant. PMID- 2929902 TI - The influence of patient characteristics on the requirements for postoperative analgesia. A reassessment using patient-controlled analgesia. AB - The requirements for analgesia after upper abdominal surgery were evaluated in 100 patients who received morphine by way of a patient-controlled analgesia system. Hourly and cumulative 24-hour requirements were analysed for possible correlations with patient characteristics and for the patterns of consumption throughout the 24-hour study period. The level of pain relief was assessed by linear analogue pain scores at 4-6 hours and 24 hours. Male patients (n = 46) required significantly more morphine than female patients (n = 54) to achieve similar levels of pain relief (p less than 0.05). There was an inverse correlation between age and morphine consumption in both males and females (r = 0.684, p less than 0.00005 and r = -0.502, p less than 0.00005 respectively). No correlation was found between morphine consumption and patient weight. The pattern of hourly morphine consumption appeared to follow a diurnal rhythm, with peak times of demand at 0900 and 2000 hours. The variations in requirements for analgesia among patients and with time of day should be taken into account when a regimen for postoperative analgesia is prescribed. PMID- 2929903 TI - Efficacy of lignocaine in the suppression of the intra-ocular pressure response to suxamethonium and tracheal intubation. AB - The effect of lignocaine pretreatment on the intra-ocular pressure response to suxamethonium and tracheal intubation was studied in 80 adult patients, divided randomly into four groups of 20 each. These groups received respectively normal saline (10 ml), lignocaine 1 mg/kg, 1.5 mg/kg and 2 mg/kg as pretreatment, in a double blind manner, one minute before anaesthetic induction with thiopentone and suxamethonium 1.5 mg/kg. Lignocaine pretreatment caused a significant decrease in intra-ocular pressure. Suxamethonium caused a significant increase, but lignocaine pretreatment in doses of 1.5 mg/kg and 2 mg/kg effectively kept the postsuxamethonium pressure below control values. Tracheal intubation further aggravated the postsuxamethonium increase in intra-ocular pressure. Lignocaine, in doses of 1.5 mg/g and 2 mg/kg also effectively kept the postintubation pressure values below control levels. Lignocaine, in dose of 1 mg/kg, only partially attenuated the postsuxamethonium and postintubation increase in intra ocular pressure. In conclusion, lignocaine pretreatment, in a dose of 1.5 mg/kg, offers protection against suxamethonium- and tracheal-intubation initiated increases in intra-ocular pressure, without causing any significant decrease in arterial pressure. PMID- 2929904 TI - Acute thyroid crisis on induction of anaesthesia. AB - Thyroid crisis on induction of anaesthesia was treated with dantrolene, because of a mistaken diagnosis of malignant hyperthermia. There was immediate improvement after dantrolene with reduction in muscle rigidity, mental confusion and pyrexia. High circulating T4 has an effect on calcium flux across the sarcoplasmic reticulum and dantrolene may inhibit this pathological mechanism. We suggest the same dosage regimen as is used in the treatment of malignant hyperthermia. PMID- 2929905 TI - Open-heart surgery in a patient with a high oxygen affinity haemoglobin variant. AB - A man in heart failure with a high oxygen affinity haemoglobin variant (Hb Rainier) underwent a mitral commissurotomy with the aid of cardiopulmonary bypass. Pre-operatively, a total blood exchange transfusion was carried out to prevent potential hypoxic and thrombo-embolic complications. No complications occurred in the postoperative period. PMID- 2929906 TI - Comparison of continuous spinal and continuous epidural anaesthesia for lower limb surgery in elderly patients. A retrospective study. AB - This retrospective study compared continuous spinal anaesthesia with continuous epidural anaesthesia for lower limb orthopaedic surgery in the elderly. The anaesthetic records of 457 patients who received continuous spinal anaesthesia and 274 who received continuous epidural anaesthesia over a 5-year period were analysed. The patients who had continuous spinal anaesthesia were at a higher anaesthetic risk (ASA 3-4, 76% as compared with 37%, p less than 0.001), but the incidence of failures was significantly lower (1.7%, as compared with 9%, p less than 0.001) and fewer patients showed a decrease in mean arterial pressure of more than 30% (44%, as compared with 65%, p less than 0.001) and (or) received vasopressors (65%, as compared with 77%, p less than 0.01). Our data show continuous spinal anaesthesia to be more reliable and to provide better cardiovascular stability. PMID- 2929907 TI - Anaesthesia and the law. Two cases of oesophageal intubation. PMID- 2929908 TI - Low-dose heparin therapy and spinal anaesthesia. PMID- 2929909 TI - Induction agent for electroconvulsive therapy. PMID- 2929910 TI - Anaesthesia and thalidomide-related abnormalities. PMID- 2929912 TI - Teaching laryngoscopy. PMID- 2929911 TI - Variables of patient-controlled analgesia. 1. Bolus size. AB - The efficacy of a range of demand doses of morphine for patient-controlled analgesia was studied. Patients who self-administered the smallest dose (0.5 mg) were frequently unable to achieve good pain control; patients who received the largest dose (2 mg) had a high incidence of ventilatory depression. A dose of 1 mg was the best increment under the conditions of this study but the relationship between increment and lockout interval requires consideration. PMID- 2929913 TI - The use of morphine in the intensive care unit. PMID- 2929915 TI - The nasocardiac reflex. PMID- 2929914 TI - Bilateral pneumothoraces after removal of a thyroglossal cyst. PMID- 2929917 TI - Subarachnoid spread of epidural local anaesthetic following dural puncture. PMID- 2929916 TI - Paralytic ileus during ketamine infusion. PMID- 2929918 TI - Inadvertent epidural midazolam and fentanyl. PMID- 2929919 TI - Multiple anaesthetics for a malignant hyperthermia susceptible patient. PMID- 2929920 TI - Perioperative dreaming in children. PMID- 2929921 TI - Epidermolysis bullosa and porphyria. PMID- 2929922 TI - Anaesthesia for carbon dioxide laser laryngeal surgery in infants. PMID- 2929923 TI - Detection of oesophageal intubation: the cola complication. PMID- 2929924 TI - Breathing bag refilling. PMID- 2929925 TI - Uncomplicated accidental early tourniquet deflation during intravenous regional anaesthesia with prilocaine. PMID- 2929926 TI - Facemask hazard. PMID- 2929927 TI - Occasional paediatric resuscitation: misuse of equipment. PMID- 2929928 TI - Postoperative absorption of controlled-release morphine sulphate. A study in patients given no parenteral opioids. AB - The absorption of morphine sulphate in a controlled-release formulation was studied in 12 patients who had undergone unilateral inguinal hernia repair under a light general anaesthetic and ilio-inguinal block. Serum morphine concentrations were measured serially and gastric emptying was assessed by measurement of paracetamol absorption. Three patients had delayed gastric emptying and impaired morphine absorption in the immediate postoperative period. Four hours later, there was a significant reduction in gastric emptying in eight patients who had normal paracetamol and morphine absorption in the immediate postoperative period. PMID- 2929929 TI - Instability of the tracheal tube in neonates. A postmortem study. AB - A postmortem study of the degree of displacement of the tracheal tube was performed on 13 neonates of varying birthweights. There was significant movement of the tube on flexion and extension of the neck, and on opening the infant's mouth. Our findings lend support to certain techniques of tracheal tube placement; the ultimate aim is to position it accurately. PMID- 2929930 TI - The oculo-emetic reflex. A rationalisation of postophthalmic anaesthesia vomiting. AB - Data related to the incidence of postoperative vomiting were collected during prospective studies on 607 ophthalmic surgical patients of all ages who underwent halothane anaesthesia with spontaneous ventilation. Analysis of data in respect of age, sex and surgical site variables, and time of onset of vomiting, identified a female sex-related vomiting incidence of about 13% and a squint related vomiting incidence of about 41%; no relationship between age and vomiting was identified. The analyses showed that squint surgery predisposed particularly to emesis, and was associated with a high incidence of both early and delayed vomiting. It is suggested that the apparent absence of an age-vomiting relationship in ocular, and especially squint, surgery, and the high incidence of vomiting, particularly the early vomiting associated only with squint surgery, provide clinical evidence for the existence of an oculo-emetic reflex. Our observations show that intra- and postoperative surgical stimulation of this oculo-emetic reflex is reflected in the incidences of vomiting after ocular surgery. PMID- 2929932 TI - Anaphylaxis due to suxamethonium in a 7-year-old child: a 14-year follow-up with allergy testing. AB - In 1973 a 7-year-old girl had anaphylactic reactions after two general anaesthetics. In-vitro testing with the leucocyte challenge histamine release test showed a strong response to suxamethonium, and other tests indirectly suggested an allergic mechanism. The conclusion was that this was an allergy to suxamethonium. Further blood was sent for testing against a range of neuromuscular blockers, but the patient was 'lost' until she re-appeared 14 years later as an antenatal patient. In-vitro testing was repeated against suxamethonium and all the available neuromuscular blockers after delivery. The radio-allergosorbent test for allergen-specific IgE antibodies was performed on newly collected serum and that which had been stored for 13-14 years. Skin testing was also performed. The results remain positive and suggest a degree of allergy to all the neuromuscular blockers with the possible exception of vecuronium. The radio-allergosorbent test was negative in the patient's baby. PMID- 2929931 TI - A new method of analgesia for relief of circumcision pain. AB - A prospective, randomised, double-blind study was designed to determine whether topical application of 2% lignocaine is effective in decreasing analgesic drug requirements during and after circumcision surgery. General anaesthesia with halothane and nitrous oxide 60-70% in oxygen was administered via a facemask and a Bain system. Administration of halothane was stopped after removal of the foreskin; lignocaine (2%) or placebo was applied topically as drops to the surface of the penis to two groups of patients. Halothane was restarted if the anaesthesia was ineffective. The intra-operative consumption of halothane was significantly less (p less than 0.05) in the treated group as compared with the placebo group (0 and 17, SEM 3, % x minute). The treated group required significantly less (p less than 0.002) pethidine after operation (5 and 10 patients), and the pain-free period was significantly longer (p less than 0.01) (41, SEM 6 and 6, SEM 2 minutes) as compared with the placebo group. PMID- 2929933 TI - Major thoracic surgery during active tetanus. AB - This report describes the anaesthetic and intensive care management of a patient who had a thoracotomy during active tetanus. The dilemmas which faced the clinicians involved with the case are discussed. PMID- 2929934 TI - Angiotensin II in the management of excision of phaeochromocytoma. AB - The management of a patient with an unusual combination of anaesthetic problems, namely phaeochromocytoma and difficult intubation is described. Angiotensin II is discussed in the management of hypotension after excision of the tumour. PMID- 2929935 TI - Epidural anaesthesia for bilateral inguinal herniorrhaphy in Eisenmenger's syndrome. AB - The successful management of a patient with Eisenmenger's syndrome undergoing bilateral herniorrhaphy is described, and some of the anaesthetic problems associated with this condition are considered. The case is reported because epidural anaesthesia is performed rarely in these patients. The use of subcutaneous heparin, the level of monitoring required, and the value of pulse oximetry are also discussed. PMID- 2929937 TI - Paediatric anaesthesia in a district general hospital. AB - Over 4000 general anaesthetics were administered during 1987 to children under the age of 13 years in the Norwich Health District. We have reviewed the 2938 anaesthetics performed in the Norfolk and Norwich Hospital. Five hundred and fifty-eight (19%) were undertaken in children aged less than 3 years; 24 of these were neonates. The implications of this workload are discussed, with reference to the more appropriate use of consultants with previous paediatric anaesthetic training, the training of junior staff and the policy for transfer of patients to specialised centres. PMID- 2929936 TI - The tumour lysis syndrome. Intensive care aspects of paediatric oncology. AB - Tumour lysis syndrome occurs when chemotherapy is started in children who present advanced lymphomas and leukaemias. Rapid cell lysis causes life-threatening metabolic derangements because of the release of intracellular potassium, phosphate and uric acid. An alkaline diuresis is commonly established before the start of chemotherapy to minimise uric acid and phosphate deposition within the kidney. Two cases are described where intravenous fluid loading resulted in acute pulmonary oedema, and the intensive care management of such cases is discussed. The improved outcome from increasingly aggressive chemotherapeutic regimens means that children with advanced tumours and organ failure may present for supportive therapy during the early stages of treatment. Close liaison between paediatric oncologists and intensive care staff is essential to establish admission criteria for patients at risk of these complications, and to define therapeutic end points in the event of multisystem failure. PMID- 2929938 TI - Anaesthesia for patients over 90 years of age. Outcomes after regional and general anaesthetic techniques for two common surgical procedures. AB - Peri-operative morbidity and mortality and long term outcome of patients over 90 years of age who underwent either total hip arthroplasty or transurethral prostate resection were studied retrospectively. The outcomes of patients who received regional or general anaesthesia were compared. One hundred and forty-one patients underwent total hip arthroplasty and 44 patients underwent transurethral prostate resection during the study period (1975-1985). Overall in-hospital mortality was 4.9% Mortality at 30 days was 5.3% in patients who underwent hip arthroplasty during regional anaesthesia, compared with 6.8% in those who received general anaesthesia. Long term survival was similar for these two groups and was longer than projected for age and gender-matched general population cohorts. The 30-day mortality rate was 3.2% for patients who underwent prostatic resection under regional anaesthesia; no deaths occurred in the general anaesthesia group. This difference was not statistically significant. Long term survival was similar for patients in both groups and was better than predicted. Anaesthetic technique did not influence short term morbidity and mortality or long term outcome for these procedures. PMID- 2929939 TI - Postdural puncture headache. A comparison between 26- and 29-gauge needles in young patients. AB - The incidence of postdural puncture headache after spinal anaesthesia with two types of 26- and 29-gauge needles was investigated in 149 patients less than 30 years old. Ten patients, (6.7%), six men and four women, developed typical symptoms of postdural puncture headache, while six (4.0%) developed headache of other origin. There were no headaches in the 29-gauge group. Spinal anaesthesia in four patients (8%) was impossible to perform with the 29-gauge needle. By using the latter, spinal anaesthesia can be given to young adults with little risk of postdural puncture headache. PMID- 2929941 TI - Confidential professional reports. A method of assessing the career progress and prospects of anaesthetic senior house officers. AB - A proforma is described which is used at 6-monthly intervals to assess the professional progress of anaesthetic senior house officers. The administration of a reporting system as part of the career counselling process is outlined, and its potential for determining the future prospects of junior staff is discussed. PMID- 2929940 TI - Intra-operative collapse or death related to the use of acrylic cement in hip surgery. AB - Six intra-operative deaths and two episodes of near-fatal hypotension occurred in 52 consecutive Hastings procedures (insertion of metal prosthesis grouted in acrylic cement) for subcapital fracture of the femoral neck. This high complication rate was identified by a system of clinical audit undertaken by members of the anaesthetic department. PMID- 2929942 TI - Second report from an anaesthetic reactions advisory service. AB - The continued work of the advisory service is reported; this now amounts to at least 300 enquiries about clinically severe adverse reactions each year. Thiopentone is still the most commonly associated intravenous induction agent with adverse reactions (76%), particularly when it is used with suxamethonium. Local anaesthetics account for between 5 and 10% reports. PMID- 2929943 TI - Health Equipment (Dis)Information: HEI 166 evaluation of heat and moisture exchangers. PMID- 2929944 TI - Plasma bupivacaine concentrations after inadvertent intravenous injection. PMID- 2929946 TI - Neonatal responses to tracheal intubation. PMID- 2929945 TI - The relevance of volatile substance abuse to anaesthetics. PMID- 2929947 TI - Dural punctures. PMID- 2929948 TI - Malignant hyperthermia and myotonia congenita (Thomsen's disease) PMID- 2929949 TI - Anaesthesia for valvuloplasty. PMID- 2929950 TI - Acute inversion of the uterus at caesarean section. PMID- 2929951 TI - Edrophonium-hyoscine butylbromide mixture in neonates. PMID- 2929952 TI - Anaesthesia in the testicular feminisation syndrome. PMID- 2929953 TI - Another tale of the unexpected. PMID- 2929954 TI - Consent and the anaesthetist--use of a videofilm. PMID- 2929955 TI - Epidural anaesthesia and instrumental delivery. PMID- 2929956 TI - Subarachnoid anaesthesia for elective Caesarean section. PMID- 2929959 TI - 'Ethics' of difficult tracheal intubation. PMID- 2929958 TI - Asynchronous independent lung ventilation. PMID- 2929957 TI - Bupivacaine and femoral nerve block. PMID- 2929960 TI - Blind nasal intubation and (or) fibreoptic guided intubation? PMID- 2929961 TI - 'Cockpit' drill. PMID- 2929962 TI - Broken laryngoscope. PMID- 2929963 TI - Sick sinus syndrome manifest after spinal anaesthesia. PMID- 2929964 TI - Bone cement. PMID- 2929965 TI - [Early prognosis in severe cranio-cerebral trauma using the Glasgow Coma Score and evoked potentials]. AB - During 72 h following severe head injury, 103 patients in acute posttraumatic coma were assessed by clinical examinations (documented by Glasgow Coma Score) and brain stem auditory evoked potentials (BAEP) as well as short-latency somatosensory evoked potentials (SEP) following median-nerve stimulation. Patient outcomes were classified at 6 months or more according to the following categories: good recovery, severely disabled or vegetative, and brain dead. Patients who had died of systemic complications (pneumonia, septicemia, renal failure, etc.) were excluded from the study. The Glasgow Coma Score was reliable in forecasting a favorable outcome; all patients with a Score over 9 points had a good recovery. The Glasgow Coma Score was not reliable in predicting an unfavorable outcome, however; some patients with the lowest possible Glasgow Coma Score (3 points) at the early clinical examination survived with good recovery. The BAEPs were reliable predictors of an unfavorable outcome; the outcome was unfavorable when a missing wave V or more missing waves pointed toward a secondary brainstem lesion. Normal BAEPs were not reliable, however, in predicting a favorable outcome. SEP data served as a prognostic indicator of unfavorable as well as favorable outcomes. In summary, evoked potentials add valuable information to the clinical examination in assessing a patient's outcome after severe head injury. PMID- 2929966 TI - [Intraoperative, direct and continuous measurement of stomach pH following pretreatment with ranitidine or sodium citrate]. AB - We carried out continuous direct pH measurements of gastric fluid in 49 female patients pretreated with 300 mg ranitidine by mouth on the evening prior to surgery and 150 mg by mouth before the operation. A further 51 women were pretreated with 30 ml sodium citrate shortly before admission to the operating room. Twenty patients received 30 ml sodium citrate via a separate gastric tube after the first pH measurement; 22 were given no premedication. In 95% of cases, 30 ml sodium citrate was found to increase the pH to over 3.5 within 5 min; a failure rate of 5% can therefore be expected. This can be explained mainly by the failure of sodium citrate to mix thoroughly with the gastric fluid. Pretreatment with ranitidine increased the pH to over 4.0 in every case, and the pH on extubation was still over 4.0 even after delayed pH on extubation was still over 4.0 even after delayed or prolonged operations. We recommend that 30 ml sodium citrate be given shortly before the beginning of emergency obstetric operations. However, we prefer ranitidine for elective operations in patients at risk for aspiration because it increases of the gastric fluid pH to at least 4.0 in every case. PMID- 2929968 TI - [An increase in intracranial pressure following fentanyl]. AB - We report an unusual fentanyl-induced reaction in an 8-year-old boy who had to be sedated and hyperventilated because of a severe head injury. Following the intravenous administration of a bolus of fentanyl, the intracranial pressure rose markedly for about 10 min. Simultaneously, the arterial blood pressure fell and heart rate increased, critically reducing the cerebral perfusion pressure temporarily. This reaction could be due to histamine-induced vasodilation. PMID- 2929967 TI - [Application of an infection control protocol at an anesthesiology intensive care unit]. AB - We studied the efficiency and practicability of a new protocol for surveillance of nosocomial infection in 99 patients admitted to our intensive care unit (ICU) between October 1985 and March 1986. The protocol contained the therapy given before admission to the ICU and daily records of: (1) therapy suspected to increase the risk of nosocomial infection (ventilatory support, operations, hemofiltration, central venous and arterial catheters, Swan-Ganz catheters, etc.); (2) parameters possibly associated with bacterial infections (white blood cell count, body temperature, platelet count, creatinine clearance, hemodynamic values, clinical suspicion of infection, suspected site of infection, pathological chest X-ray, etc); and (3) bacteriologic data (results of cultures from blood, tracheal aspirate, urine, wound secretions) and antibiotic treatment. Sepsis was diagnosed in 28 patients, and 28 had positive blood cultures; these two groups were not identical. Twenty-nine patients died, more than half of them having a serious nosocomial infection. Factors associated with nosocomial infection were: fever greater than 38.5 degrees C, recurrent fever, leucocytosis, leucopenia, thrombocytopenia; duration of stay at the ICU; ventilatory support, operations, mass transfusions, and therapy with catecholamines. Use of a Swan Ganz catheter and hemofiltration were associated with nosocomial infection, but they were usually begun after the clinical onset of sepsis. Therapy administered before admission to the ICU was not associated with nosocomial infection. Bacterial colonization of tracheal aspirate was detected in 2/3 of the ventilated patients. The most common bacteria isolated were staphylococci in blood cultures. Pseudomonas sp. and Candida albicans in tracheal secretions, and Candida albicans in urine cultures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2929969 TI - [Postoperative malignant hyperthermia in a 7-day-old infant?]. AB - A 7-day-old male newborn developed malignant hyperthermia postoperatively (uncomplicated surgical reposition of a local skull impression caused by birth trauma; general anesthesia with succinylcholine and halothane/N2O). The clinical course was typical (body temperature up to 43.7 degrees C) and led to death 30 h after anesthesia. It is emphasized that malignant hyperthermia may occur unexpectedly in the postoperative period, so that all medical personnel on surgical wards, especially in pediatrics, should be able to diagnose this life threatening disease as soon as possible and provide adequate therapy with dantrolene. PMID- 2929970 TI - [Hyperthermic reaction in the perioperative phase in 2 children with acute lymphoblastic leukemia of B-cell type]. AB - Acute lymphatic leukemia (ALL) represents one of the most frequent malignancies in childhood. Central venous access ports or partly implanted silicone catheters are usually placed for high-dose chemotherapy in these children. We report two patients aged 7 and 3 years with acute lymphoblastic beta-cell leukemia (B-ALL), a less common subtype of ALL, which presented with hyperthermia (38.4 degrees C and 39 degrees C) during anesthesia with isoflurane for implantation of a central venous catheter. The hyperthermic reactions were accompanied by an increase in expired CO2 and acidosis as well as moderate elevation of heart rate and blood pressure. As in both patients the history and preoperative findings did not reveal signs of infection or other causes of fever, the observed alterations were interpreted as symptoms of malignant hyperthermia triggered either by succinylcholine or isoflurane, which were used in both children. In addition, the hyperthermia responded to administration of dantrolene sodium according to dose recommendations for treatment of malignant hyperthermia. In one of the patients, withdrawal of dantrolene during the initial postoperative hours was followed by a recurrent increase in body temperature, which once again could be suppressed by additional dantrolene infusion. According to the literature, malignant hyperthermia has occasionally been described in children with malignancies such as leukemia or Burkitt's lymphoma. Our observations indicate that children with B ALL may be especially susceptible to malignant hyperthermia. Close monitoring of body temperature and expiratory CO2 are therefore indicated in these children, and dantrolene therapy should be started immediately in case of increased temperature during anesthesia. PMID- 2929971 TI - [Monitoring critically ill patients during transport by helicopter using a patient with abdomen apertum as an example]. AB - Noninvasive continuous monitoring systems are newly emerging as an important means of monitoring during transports in emergency care, e.g. transportation by helicopter. While automatic oscillometric blood pressure monitors have been used in the perioperative area for some time, a similar development can be observed in the field of emergency care and transportation with the availability of light, portable and battery operated systems. For monitoring adequate oxygenation, pulse oximeters have recently been brought into discussion for both the perioperative period and the transport of critically ill patients. In contrast to well established monitoring techniques during helicopter transports (ECG, inspection, manually measured blood pressure (BP), pulse oximetry reveals an oxygen deficiency due to respiratory and cardiocirculatory problems, enabling precious time to be saved. This concept is illustrated during the helicopter transport of a critically ill patient with abdomen apertum caused by Clostridium perfringens infection. Even with a critical look at the already described mishaps of this method--e.g. overestimation of true O2 saturation (sO2) and additional overestimation caused by Hb-derivatives--pulse oximetry was found to be superior to the established monitoring techniques. Furthermore, oscillometric blood pressure detection was very satisfactory during the 30-min helicopter transport. Based on our results, we believe pulse oximetry and automatic oscillometric BP measurement to be useful for monitoring during transports in helicopters, thus improving patient safety. PMID- 2929972 TI - [Thermoanalytic studies of bundles of collagen fibers with biomechanical methods]. AB - Thermomechanical experiments were performed on collagenous fibre bundles of tendons from cattle and man. Subsequent to extensions of fibre bundles the particular amount of length was kept constant (isometric conditions). At the end of the relaxation under approximative equilibrium conditions (mechanical steady state phase) the temperature was raised proportional to time (with linear temperature rate). In the range between 0 and 43 degrees Celsius the isometric force decreased in form of an approximately straight line. This line was declined at 43 degrees C (thermal depression region). After the thermal shrinkage region (62-64 degrees C) the isometric force increased considerably. In this ascending part of the isometric thermal mechanogram 2 domains of slope can be observed. They are designed as lower and upper thermal transition region. In the ascending part of the isometric thermal mechanogram an isothermal relaxation is to be seen under constant temperature conditions. The isothermal isorheological line and isothermal superelevation are described. The results are discussed in context with their meaning for functional anatomy, muscle physiology, supercoolings, and burnings. PMID- 2929973 TI - [The functional morphology of the maxillomandibular apparatus of the miniature swine MINI-LEWE. 9. Metric studies of the skull and mandible]. AB - Skull and jaw growth are described mathematically as a dynamic process. Graphs of the growth process show that basically the rate of growth decreases monotonically with increasing age. The maximum rate of growth was recorded at the time of eruption of the deciduous dentition during the first 4 months of life. As expected, the changes in the measured angles were greatest during the first 3 or 4 months after birth. PMID- 2929974 TI - Structure of the external retina of the oviparous, hermaphroditic fish Rivulus marmoratus Poey. AB - The external retina of the oviparous, hermaphroditic fish Rivulus marmoratus was examined ultrastructurally. The outer nuclear layer is about half as thick as the inner nuclear layer, and a single layer of ganglion cells is present. Single and double cones are present and these are arranged in a square mosaic. The pigment epithelium is not very well developed and extends only to the level of the cone ellipsoids in the light-adapted retina. However, the sparse pigment granules do migrate in response to light and are capable of isolating cone outer segments. Cone synaptic ribbons show extreme changes in length. The pigment epithelium contains myeloid bodies, which show variations with the photic state; and structures reminescent of phagosomes but without the limiting membrane. The structure of the external retina of R. marmoratus is discussed in relation to its behaviour and habitat. PMID- 2929975 TI - Nimodipine and the "no-reflow phenomenon"--experimental triumph, clinical failure? PMID- 2929976 TI - Effects of nimodipine on cerebral blood flow and cerebrospinal fluid pressure after cardiac arrest: correlation with neurologic outcome. AB - Fifty-one patients were included in a blind randomized study to evaluate whether the Ca-blocker nimodipine could influence cerebral blood flow (CBF) or cerebrospinal fluid pressure (CSFP) during the cerebral hypoperfusion period that follows resuscitation from cardiac arrest and to determine whether changes in CBF correlate with neurologic outcome. CBF measured 1 to 4 hours after arrest with the use of 133Xe intravenous was significantly greater with nimodipine than with placebo (27 +/- 3 versus 13 +/- 1 ml.100 g-1.min-1 at 3 hours), but with no significant difference at 24 hours. There was no clinical evidence of seriously increased CSFP in any patient in either group the first 48 hours. Mean arterial pressure was significantly lower (86 +/- 4 versus 101 +/- 4 mm Hg at 3 hours), and antiarrhythmic drugs were used significantly less frequently in the nimodipine group than in the placebo group. Twelve patients in each group eventually regained consciousness. There was no significant difference in neurologic status between the two groups at any point, and no positive correlation between CBF in the hypoperfusion period and neurologic outcome. PMID- 2929977 TI - The response of anesthesia trainees to simulated critical incidents. AB - Using a comprehensive anesthesia simulation environment (CASE 1.2) we studied the response of anesthesia trainees (10 first-year residents and 9 second-year residents) to five simulated critical incidents: 1) endobronchial intubation; 2) kinked IV; 3) atrial fibrillation with hypotension; 4) breathing circuit disconnection; 5) cardiac arrest. Simulations were videotaped, and the response times for detecting and initiating correction of the problems were measured. Different problems had significantly different response characteristics. Breathing circuit disconnection and cardiac arrest were quickly detected (21 +/- 17 seconds; 7 +/- 5 seconds), and correction was begun quickly, although major errors in managing the cardiac arrest occurred in 58% of cases. Endobronchial intubation and atrial fibrillation took longer than the other problems to detect (105 +/- 142 seconds; 111 +/- 158 seconds) and to correct (555 +/- 358 seconds; 365 +/- 121 seconds). Intravenous kink was detected more slowly (238 +/- 269 seconds) but once discovered was quickly corrected. The response of different individuals was highly variable; experience level was a significant factor for correction (P = 0.03) but not for detection of problems overall. Because of high individual variation, experience was not a significant factor in correcting any signal problem. The data suggest that some types of problems are harder to handle than others and that individuals vary widely in their problem-handling abilities. Experience is a beneficial factor in anesthesia problem solving but not in a simple fashion. Vigilant detection of problems is only the first step in a complex response pathway that might be strengthened by improved protocols and repeated practice. PMID- 2929978 TI - Variation in the resting metabolic rate of mechanically ventilated critically ill patients. AB - There has been increasing interest in the nutritional support of the critically ill patient. The day-to-day variation in resting energy expenditure (REE) was studied over a 3-5-day period in 17 postoperative mechanically ventilated critically ill patients to gain insight as to how often caloric intake should be reassessed, whether changes observed over 3-5 days are of sufficient magnitude to make frequent adjustments in caloric intake, and what factors are associated with large alterations in metabolic rate. REE was measured daily for 3-5 days, and the percent variation in REE [(highest REE--lowest daily REE)/(lowest daily REE) x 100] calculated. The variation ranged from 4 to 56%, and on further analysis two distinct groups were identified, one with a mean variation of 12 +/- 4% (SD) (range 4-18%) and the other with a mean variation of 46 +/- 8% (range 37-56%). The former group was clinically stable, whereas the latter was not. Clinically stable patients need less frequent measurements than those who are more ill, but when designing a nutritional regimen for them, at least 20-25% should be added to the REE, 15% to account for day-to-day variation and 5-10% for activity. PMID- 2929979 TI - The effect of sublingual nifedipine on coronary venous graft resistance immediately following cardiopulmonary bypass. AB - The purpose of this study was to determine the effects of sublingual nifedipine administered immediately after discontinuation of cardiopulmonary bypass on coronary graft resistance and systemic hemodynamics. Twenty patients were prospectively randomized into two groups; one given 10 mg sublingual nifedipine after weaning from bypass, the other given a placebo. Coronary graft blood flow was measured under blinded conditions and graft resistance calculated from measurements obtained with an electromagnetic flow probe applied directly to the graft prior to and 15 minutes after drug administration. Serum nifedipine levels were determined immediately before and 15, 30, and 60 minutes after sublingual administration. All patients receiving nifedipine had therapeutic serum levels. Graft resistance in patients given nifedipine decreased a statistically significant average of 27% and increased slightly, but not statistically significantly so, in patients given sublingual placebos. There were no differences between the two groups in cardiac index or pulmonary capillary wedge pressures. We conclude that the administration of sublingual nifedipine to patients in the immediate postbypass period results in therapeutic serum nifedipine levels and decreases coronary graft resistance without affecting cardiac performance. PMID- 2929980 TI - Hemodynamic effects of dobutamine in patients following mitral valve replacement. AB - Mitral valve replacement is frequently complicated by a low cardiac output syndrome and elevated pulmonary arterial pressures. In the present study, we used dobutamine to increase cardiac index and measured the pulmonary hemodynamic effects in 10 patients with increased pulmonary vascular tone following mitral valve replacement. Using increasing doses of dobutamine up to 10 micrograms.kg 1.min-1, we observed a statistically significant increase in mean cardiac index (from 2.39 +/- .14 liters.min-1.m-2 to 3.52 +/- .33, P less than 0.01) and mean heart rate (from 71.6 +/- 5.2 beats.min-1 to 84.3 +/- 8.1, P less than 0.01). This was associated with stable mean systemic arterial pressures and mean pulmonary arterial pressures. Both mean systemic and pulmonary vascular resistances decreased significantly (from 1210 +/- 99 dynes.sec.cm-5 to 809 +/- 90 [P less than 0.01], and from 195.9 +/- 30.6 dynes.sec.cm-5 to 129.4 +/- 41.2 [P less than 0.01] respectively) with dobutamine. Intrapulmonary shunt flow increased significantly in the five patients studied. Though increases in heart rate and pulmonary shunt flow may limit it use, dobutamine increases cardiac output and decreases pulmonary vascular resistance in patients with increased pulmonary arterial pressure following mitral valve replacement. PMID- 2929981 TI - Pseudocholinesterase activity in human cerebrospinal fluid. AB - Pseudocholinesterase (PCHE) activity and dibucaine numbers (DN) in the cerebrospinal fluid (CSF) and plasma of 10 ASA physical status 1 and 2 patients were measured using a kinetic method. CSF had a mean PCHE activity of 0.018 +/- 0.013 unit/ml with a DN of 59 +/- 4. Whereas, PCHE activity and DN in the plasma were 0.960 +/- 0.12 units/ml and 84 +/- 3, respectively. We also measured PCHE activity and DN in the CSF and plasma of 4 patients in whom there was a recent history of intraventricular bleeding. These patients had a CSF PCHE activity of 0.340 +/- 0.07 units/ml (DN = 78 +/- 3) and a plasma PCHE activity of 0.950 +/- 0.10 units/ml (DN = 82 +/- 2). Our data show that there is a low activity of PCHE in CSF, 1/20-1/100th that of plasma. Our data also show that PCHE activity increased to 1/4 to 1/2 that of plasma in CSF of patients with bleeding into CSF. PMID- 2929982 TI - Needle direction affects the sensory level of spinal anesthesia. AB - The effect of the direction of the spinal needle on the sensory level of anesthesia was investigated. Three ml plain bupivacaine 0.5%, previously equilibrated to 37 degrees C, were injected intrathecally in two groups of twenty patients, who were kept sitting for three minutes after injection. In patients in group 1 a paramedian approach was used with an angle between the spinal needle and the patient's back of 50 degrees or less. In patients in group 2 a median or paramedian approach was used, the resultant angle between the spinal needle and the patient's back being between 70 degrees and 100 degrees. The differences between segmental levels of sensory loss between groups 1 and 2 (T 3.4 and T 5.1, respectively) and of temperature loss (T 2.6 and T 4.2, respectively) 30 minutes after injection of bupivacaine were statistically significant. It is concluded that a steep paramedian approach of the subarachnoid space with an angle of less than 50 degrees results in a cephalad spread averaging about 1.6 segments greater than when the needle is in the perpendicular position. PMID- 2929983 TI - Effect on airway resistance of ketamine by aerosol in guinea pigs. AB - The effect of aerosolized ketamine hydrochloride was investigated by measuring airway resistance with a two-compartment plethysmograph in guinea pigs challenged with histamine. In the first phase of the study, treatment with ketamine prior to histamine challenge did not protect against elevation of airway resistance. In the second phase of the study, ketamine inhalation after histamine challenge did not significantly diminish airway resistance. Aerosolized ketamine is not recommended for use in human subjects with asthma. PMID- 2929984 TI - Isoflurane anesthesia in sandhill cranes (Grus canadensis): minimal anesthetic concentration and cardiopulmonary dose-response during spontaneous and controlled breathing. AB - Information on species differences in responses to inhalation anesthetics has been established in a variety of mammalian and non-mammalian species, but comparable studies have not been reported in birds. The purpose of this study was to determine minimal anesthetic concentration and cardiopulmonary concentration response effects of isoflurane in Sandhill cranes. Six cranes were anesthetized with isoflurane in oxygen. Gases sampled through a polyethylene tube inserted to the distal end of an endotracheal tube were used for measurements of isoflurane concentrations using an infrared gas analyzer. Body temperature was maintained at 40 +/- 0.5 degrees C. The minimal anesthetic concentration for isoflurane was determined during spontaneous ventilation, and concentration-response data were collected at 1, 1.5, and 2.0 times the minimal anesthetic concentration. Concentration-response data were repeated during mechanically controlled breathing with PaCO2 maintained between 27 and 35 mm Hg. The minimal anesthetic concentration for isoflurane was 1.34 +/- 0.14 vol% (mean +/- SD). Concentration dependent respiratory depression during spontaneous breathing was evidenced in all cranes by an increase in PaCO2. Isoflurane induced apnea in two of the cranes during spontaneous ventilation at 2 times the minimal anesthetic concentration. As the concentration of isoflurane was increased, mean arterial blood pressure decreased during both spontaneous and controlled ventilation. Mean arterial blood pressure was higher during controlled ventilation than during spontaneous ventilation. The minimal anesthetic concentration for isoflurane in Sandhill cranes is similar to values for isoflurane minimal anesthetic concentration in mammals. Isoflurane has dose-dependent effects on cardiopulmonary function qualitatively similar to those observed in mammals. PMID- 2929985 TI - Oral fiberoptic intubation over a retrograde guidewire. PMID- 2929986 TI - Can epidural fentanyl control autonomic hyperreflexia in a quadriplegic parturient? PMID- 2929987 TI - Minimal effective dose of intrathecal morphine for pain relief following transabdominal hysterectomy. PMID- 2929988 TI - Effects of metaraminol on the resistance and capacitance vessels in humans. PMID- 2929989 TI - Spinal needles. PMID- 2929990 TI - Hypoventilation caused by ventilator valve rupture. PMID- 2929991 TI - Nail polish and oximetry. PMID- 2929992 TI - Practice standards: the Midas touch or the emperor's new clothes? PMID- 2929993 TI - Prevention of intraoperative anesthesia accidents and related severe injury through safety monitoring. AB - Among 1,001,000 ASA Physical Status I and II patients (a subset of the 1,329,000 anesthetics administered from 1976 through mid-1988 in the nine component hospitals of the Harvard Department of Anaesthesia), there were 11 major intraoperative accidents solely attributable to anesthesia (five deaths, four cases of permanent CNS damage, and two cardiac arrests with eventual recovery) among the 70 cases reported to the insurance carrier. Review of these accidents revealed that unrecognized hypoventilation was the most common cause (seven cases). These seven accidents and one other due to discontinuation of inspired oxygen in all likelihood would have been prevented by appropriate response to earlier warnings generated by the "safety monitoring" principles mandated by the Harvard minimal monitoring standards. Analysis suggests capnography (although not mandated) would be the best monitor of ventilation. An important associated issue was the apparent inadequacy of supervision of residents and C.R.N.A.s. The eight preventable accidents represent 88% of the projected insurance payout. Only one accident occurred after the 1985 adoption of the standards (in the month following their implementation). From that time through mid-1988, there have been 319,000 anesthetics without a major preventable intraoperative injury. Although not statistically significant, the accident rate in the target population of healthy people is reduced more than threefold. This and the case analyses support the contention that nearly all the inevitable mishaps (technical or from errors in judgement) that occur during anesthesia can be identified through safety monitoring early enough to prevent most major patient injuries. This improved clinical outcome should lessen the medical-legal and malpractice insurance burdens of anesthesiologists. PMID- 2929994 TI - Manual evaluation of residual curarization using double burst stimulation: a comparison with train-of-four. AB - Double burst stimulation (DBS) is a new mode of stimulation developed to reveal residual neuromuscular blockade under clinical conditions. The stimulus consists of two short bursts of 50 Hz tetanic stimulation, separated by 750 ms, and the response to the stimulation is two short muscle contractions. Fade in the response results from neuromuscular blockade as with train-of-four stimulation (TOF). The authors compared the sensitivity of DBS and TOF in the detection of residual neuromuscular blockade during clinical anaesthesia. Fifty-two healthy patients undergoing surgery were studied. For both stimulation patterns the frequencies of manually detectable fade in the response to stimulation were determined and compared at various electromechanically measured TOF ratios. A total of 369 fade evaluations for DBS and TOF were performed. Fade frequencies were statistically significantly higher with DBS than with TOF, regardless of the TOF ratio level. Absence of fade with TOF implied a 48% chance of considerable residual relaxation as compared with 9% when fade was absent with DBS. The results demonstrate that DBS is more sensitive than TOF in the manual detection of residual neuromuscular blockade. PMID- 2929995 TI - The patient's position influences the incidence of dysrhythmias during pulmonary artery catheterization. AB - To determine the influence of a patient's position on the incidence of dysrhythmias during pulmonary artery catheterization, 34 adult patients scheduled for elective coronary artery bypass graft surgery and pulmonary artery catheterization were studied. All introducers were inserted via the right internal jugular vein using the Seldinger technique with the patient in the Trendelenburg position. For each patient, the pulmonary artery catheter was advanced twice: once while the patient was in the Trendelenburg (T) position with a 5-10 degrees head-down tilt and another with a 5 degrees head-up and right lateral tilt (R) position. In 13 of the 68 pulmonary artery catheter passages, no dysrhythmias were noted. In 13 patients, a change in dysrhythmia classification was noted between the two positions. In 11 of the 13 patients, the dysrhythmia classification changed from malignant in the Trendelenburg position to benign or absent in the right lateral tilt position. Although the incidence of dysrhythmias was similar in both groups, the Trendelenburg position was associated with a significantly higher incidence of malignant dysrhythmias than the right tilt position (P less than 0.05). The authors conclude that the head-up and right lateral tilt position appears superior to the Trendelenburg position for passage of the pulmonary artery catheter in the awake patient scheduled for elective coronary bypass surgery. PMID- 2929996 TI - Increased intraoperative cardiovascular morbidity in diabetics with autonomic neuropathy. AB - Thirty-eight consenting subjects scheduled for elective ophthalmologic surgery were classified as nondiabetics (n = 21) or diabetics (n = 17) and were tested preoperatively for autonomic dysfunction. The autonomic tests consisted of respiratory sinus arrhythmia and heart rate responses to the Valsalva maneuver to test cardiac vagal function and diastolic blood pressure responses to head-up tilt and cold pressor test to assess sympathetic efferent integrity. At a separate time, anesthesia was established with fentanyl (2 micrograms/kg), sodium thiopental (3-5 mg/kg), and vecuronium (0.1 mg/kg), and maintained with isoflurane, oxygen, and nitrous oxide. An anesthesiologist, blinded to the autonomic test results, recorded perioperative blood pressure and heart rate. The autonomic test results revealed significant autonomic dysfunction among the diabetics. Heart rate and blood pressure declined to a greater degree (P less than 0.05) during induction of anesthesia in diabetics compared with controls and there was less of an increase in these same parameters following tracheal intubation in diabetic patients. Thirty-five percent of diabetics required intraoperative vasopressors compared with only 5% of control patients (P less than 0.05). A major finding was that the diabetics who required intraoperative blood pressure support had significantly greater impairment of autonomic test results compared with those diabetics who did not need vasopressors. Diabetics are at increased risk for cardiovascular lability during anesthesia and preoperative screening of diabetics with simple noninvasive autonomic tests may be useful in identifying those at high risk for perioperative cardiovascular instability. PMID- 2929997 TI - Low-dose intramuscular ketamine for anesthesia pre-induction in young children undergoing brief outpatient procedures. AB - The authors sought to determine whether intramuscular ketamine (2 mg/kg) would facilitate inhaled induction of anesthesia in those children who are uncooperative. Thirty-five children were anesthetized with halothane and nitrous oxide for insertion of tympanotomy tubes. Twenty of those children were deemed by the anesthesiologist to be uncooperative and received 2 mg/kg of ketamine im prior to induction of anesthesia. The onset time (time from ketamine administration until induction of inhaled anesthesia could be started) was 2.7 +/ 0.3 min. The quality of the subsequent acceptance of inhaled induction with halothane was excellent in 61% of the patients and adequate in the remaining 39%. The recovery and discharge times were compared with those observed in 15 matched children who accepted induction of anesthesia via a mask without the use of ketamine. Recovery time was not prolonged, but home discharge was delayed by an average of 13 min in the ketamine group (P less than 0.04). Low-dose im ketamine was found to be an acceptable pre-induction drug in young children who are uncooperative for an inhaled induction of anesthesia. PMID- 2929998 TI - Femoral nerve blockade in children using bupivacaine. AB - The authors evaluated the efficacy and incidence of side effects from blockade of the femoral nerve with 0.5% bupivacaine in 14 children with fracture of the middle third of the femoral shaft. In nine of these children, a pharmacokinetic analysis was also performed. The onset of analgesia occurred in 8.0 +/- 3.5 minutes after blockade of the femoral nerve. One block failed, resulting in iv narcotics being administered to alleviate the pain. In the remaining 13 children, pain decreased to nonexistent in 11 of the children and only mild pain with movement in the remaining two children. The level of analgesia did not change when the children underwent radiographic examination (60 +/- 18 min after the femoral nerve block) and application of traction (124 +/- 19 min after femoral nerve block). The maximum bupivacaine plasma concentration was 0.89 +/- 0.37 microgram/ml, obtained 24.4 +/- 12.6 min after the end of the injection. The femoral nerve blockade with bupivacaine provides prompt, effective, and prolonged analgesia in children suffering from fractures of the femoral shaft, allowing transport, radiographic examination, and application of traction in optimal conditions. Although the sample size was small, the side effects appeared to be rare. PMID- 2929999 TI - Pharmacokinetics of intravenous dantrolene in children. AB - To determine the pharmacokinetics of iv dantrolene and its metabolites in children, ten children 2-7 yr of age scheduled for minor elective surgery, were studied. After induction of anesthesia and tracheal intubation, dantrolene (2.4 mg/kg) was administered iv over 10.2 +/- 0.83 min. Venous blood samples (3 ml) were obtained 1, 5, 10, 20, and 30 min and 1, 2, 4, 8, 12, and 20 h after the dantrolene infusion. Whole blood concentrations of dantrolene, 5 hydroxydantrolene, and nitroreduced acetylated dantrolene were measured by high performance liquid chromatography. The whole blood concentration of dantrolene decreased rapidly from a mean (+/- SD) of 6.03 +/- 0.93 microgram/ml 1 min after the end of the dantrolene infusion to 3.56 +/- 0.49 microgram/ml at 1 h. Between 1 and 4 h, the concentration of dantrolene either remained constant or increased slightly. Thereafter, the concentration of dantrolene decreased slowly with an elimination half-life (mean +/- SD) of 10.0 +/- 2.6 h. The mean (+/- SD) time for the concentration of dantrolene to decrease to 3.0 micrograms/ml was 6.55 +/- 2.88 h. The whole blood concentration of 5-hydroxydantrolene reached a maximum of 0.60 +/- 0.18 microgram/ml approximately 7 h after the dantrolene and decreased thereafter with an elimination half-life of 9.0 +/- 2.5 h. The concentration of nitroreduced acetylated dantrolene was below the limit for detection at all times. All children recovered without complications. Intravenous dantrolene, 2.4 mg/kg, produces safe and predictable blood concentrations in children similar to those reported in adults. PMID- 2930000 TI - Alveolar-to-arterial-to-venous anesthetic partial pressure differences in humans. AB - To determine the correlation between the partial pressures of anesthetics in venous and arterial blood (Pv and Pa), and to assess whether this correlation was better than that between the partial pressure of anesthetic in alveolar gas (PA) and Pa, isoflurane (n = 4) or halothane (n = 4) was administered to eight patients undergoing surgery, and Pv, PA, and Pa were measured. PA correlated with Pa better than did Pv (R = 0.960 vs. 0.878), and there was less variability in the data. Differences between Pv and Pa increased as the relative blood flow to the hand decreased [indicated by an increasing arterial-to-venous (a-v) O2 content difference]. The difference between PA and Pa was approximately 20% of the difference between inspired gas (PI) and Pa. The differences between PA and Pa appear to be due primarily to contamination of alveolar gas by physiologic dead space gas. PMID- 2930001 TI - New discharge criteria decrease recovery room time after subarachnoid block. AB - The authors completed a two-phase study to determine criteria that might predict hemodynamic stability during recovery from subarachnoid block (SAB). Patients' supine and sitting (2 min) blood pressures were determined at 30-min intervals in the recovery room (RR). In the first group of 26 patients, retrospective analysis revealed that the orthostatic decrease in mean arterial pressure (MAP) never exceeded 15% following two successive orthostatic decreases of 10% or less. This finding was validated prospectively in a second group of 26 patients. Following two successive orthostatic MAP decreases of 10% or less, none of 65 orthostatic challenges resulted in an MAP decrease of more than 15%; conversely, in the absence of two successive MAP decreases of less than 10%, 5 of 51 orthostatic challenges resulted in an MAP decrease of greater than 15% (P less than 0.02). Had patients been discharged from the RR based on two successive MAP decreases of less than 10%, 35 of 52 patients could have been discharged from the RR 76 +/- 6 min (mean +/- SE) sooner than they would have under usual empirical discharge criteria of supine hemodynamic stability, regression of sensory level to T10, and return of toe movement. Following SAB, hemodynamic stability may return before sensory and motor function; for many patients, orthostatic testing following SAB may safely decrease the amount of time spent in the RR. PMID- 2930002 TI - The role of oxidative biotransformation of halothane in the guinea pig model of halothane-associated hepatotoxicity. AB - The role of the oxidative pathway of halothane biotransformation in mediating the hepatotoxicity of halothane in the guinea pig was examined by utilizing the deuterated form of halothane (d-halothane), which is resistant to oxidative metabolism. Male outbred Hartley guinea pigs were exposed to either 1% v/v halothane or d-halothane, FIO2 = 0.21, for 4 h. Significant reductions in both oxidative and overall halothane biotransformation were observed with the use of d halothane as indicated by decreased plasma levels of trifluoroacetic acid and bromide ion, respectively, immediately following exposure. Plasma fluoride ion, indicative of the reductive metabolism of halothane, was significantly increased with the use of d-halothane. These changes in metabolism were accompanied by a reduced hepatotoxic response as indicated by significantly decreased plasma ALT levels 24-96 h following exposure and a significantly lesser incidence of centrilobular necrosis. Thus, the oxidative biotransformation of halothane is implicated as a mechanism of injury in guinea pigs. PMID- 2930003 TI - Acetylcholine receptor density and acetylcholinesterase activity in skeletal muscle of rats following thermal injury. AB - Thermal injury causes systemic changes that result in altered sensitivity to many drugs including nondepolarizing muscle relaxants. In an effort to identify the mechanism(s) responsible for the resistance to nondepolarizing muscle relaxants, the density of acetylcholine receptors (AChR) and the activity of acetylcholinesterase (AChE) were determined in rats following a 30% total body surface thermal injury at a time when resistance to atracurium is maximum. AChR density in gastrocnemius and diaphragm was unchanged by thermal injury. Furthermore, the ratio of junctional to extrajunctional AChR in diaphragm was unaltered. Total AChE activity was unchanged in thermally injured rats compared with that in sham-injured animals. Separation of the molecular forms of AChE by sucrose gradient centrifugation also showed no changes in the relative proportions of these species. The mechanism of resistance to nondepolarizing muscle relaxants does not appear to be explained by changes in AChR number or changes in the activity of AChE. PMID- 2930004 TI - Effects of halothane on left ventricular relaxation and early diastolic coronary blood flow in the dog. AB - The effects of graded concentrations of halothane on left ventricular relaxation and phasic coronary blood flow (CBF) were studied in six open-chest, anesthetized dogs. Global and regional left ventricular function were measured. Besides the expected dose-dependent depression of contractility, regional shortening, and cardiac output, halothane caused significant increases in the time constant of relaxation (Trelax), and decreased and delayed the nadir of peak negative left ventricular dP/dt. Dose-dependent reductions of CBF were noted. Percentage CBF during isovolumic relaxation was significantly reduced and showed a strong inverse correlation with Trelax. Halothane appears to interfere with the inactivation process of the heart; this in turn may impede the early rise in CBF during isovolumic relaxation. PMID- 2930006 TI - Effects of isoflurane on contractile properties of diaphragm. AB - Isoflurane has been shown to depress skeletal muscle force in vitro, but data are not available regarding the effects of isoflurane on diaphragmatic muscle function in vivo. To answer this question, 15 rats anesthetized with pentobarbital and mechanically ventilated were studied. They were divided into three groups of five animals each, according to the administered concentration of isoflurane. Diaphragmatic function was assessed by measuring the transdiaphragmatic pressure (Pdi) generated during bilateral supramaximal phrenic nerve stimulation at 0.5 Hz, 20 Hz, 50 Hz, and 100 Hz under quasi-isometric conditions. After a control measurement (C), isoflurane was administered at a constant concentration (0.5, 1, or 1.5 MAC) and Pdi measurements were repeated after 30 min of isoflurane exposure (T1) and 30 min after discontinuing isoflurane (T2). In the group breathing 1.5 MAC isoflurane, the time constant of diaphragmatic relaxation (tau) and integrated electrical activity of the diaphragm (Edi) were also assessed. The Pdi amplitude generated by single twitch (0.5 Hz) was unchanged at the three isoflurane concentrations. A significant increase in Pdi at 20 Hz was observed at T1, which returned to control after 30 min recovery (T2). No change in Pdi during 50 Hz stimulation was noted during 0.5 and 1 MAC isoflurane exposure, whereas it was reduced at T1 during 1.5 MAC. For 100 Hz stimulation, a significant decrease in Pdi was noted for all groups at T1, which returned toward control values at T2. Edi was markedly reduced for 50 and 100 Hz stimulation, but this reduction was also transient, since Edi returned toward control values at T2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2930005 TI - Primate brain tolerance to temporary focal cerebral ischemia during isoflurane- or sodium nitroprusside-induced hypotension. AB - Isoflurane has properties that suggest it may provide cerebral protection from ischemia. This study compared, in primates, neurologic outcome after a 45-min period of temporary focal ischemia during hypotension induced with either isoflurane or sodium nitroprusside (SNP). Fourteen macaque monkeys were studied. Seven animals received halothane and seven isoflurane anesthesia during surgical preparation. After transorbital exposure of the middle cerebral artery (MCA), in the halothane group, the inspired halothane was reduced to 0.75% and the mean blood pressure (BP) reduced to 50 mmHg by the infusion of SNP. In the isoflurane group, the isoflurane was titrated to reduce mean BP to 50 mmHg. Stable hypotension was maintained for 90 min, which included a 45-min period of MCA occlusion. Monitoring included intraarterial blood pressure, arterial blood gases, EEG, somatosensory evoked potentials (SEP), and temperature. After the procedure the animals were allowed to awaken and were assessed neurologically every 8 h. On the third postoperative day, they were reanesthetized and underwent magnetic resonance imaging (MRI) and SEP recording. Thereafter, they were killed with iv KCl and the brains fixed for neuropathology. All animals survived the surgical procedure, but two animals receiving halothane and none receiving isoflurane died prematurely (P less than 0.2). The SEP disappeared in all animals within 10 min of MCA occlusion and then returned partially or completely. There was no difference between groups in neurologic scores, in the size of the lesion as assessed by MRI (isoflurane 15.7 +/- 6%, halothane/SNP 10.5 +/- 4%), or in the extent or severity of the neuropathologic lesions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2930007 TI - Diazepam--morphine hypnotic synergism in rats. AB - The effect of diazepam-morphine combination on the righting reflex was studied in rats. Doses of the drugs given alone and in combination that block righting reflex (RR ED50) were determined with a probit procedure. Brain concentrations following equieffective doses of the drugs administered separately and in combination were determined by radioimmunoassay. Equieffective intravenous doses and corresponding brain concentrations for the agents were compared with fractional (algebraic) and isobolographic analyses. Interaction between diazepam and morphine was found to be synergistic. It is not likely to be pharmacokinetic in nature. PMID- 2930008 TI - The 27th Rovenstine Lecture: Neuroanesthesia and the achievement of professional respect. PMID- 2930009 TI - Fatal air embolism following anesthesia for insertion of a peritoneovenous shunt. PMID- 2930010 TI - The diagnosis of phrenic nerve block on chest X-ray by a double-exposure technique. PMID- 2930011 TI - Intraoperative management of penile erection by using terbutaline. PMID- 2930012 TI - Air embolism removal from both pulmonary artery and right atrium during sitting craniotomy using a new catheter: report of a case. PMID- 2930013 TI - Anesthetic considerations for Beckwith-Wiedemann syndrome. PMID- 2930015 TI - Are insurance premiums related to use of technology? PMID- 2930014 TI - Hemodynamic effects of prostaglandin E2. PMID- 2930016 TI - The pH adjustment of 2-chloroprocaine hastens the onset of epidural analgesia. PMID- 2930017 TI - A complication associated with the use of midazolam. PMID- 2930018 TI - Postoperative apnea. PMID- 2930019 TI - [Quantitative analysis of apolipoproteins and lipoprotein particles in patients with head injuries]. AB - By head-injured patients, apo A-I and apo A-II concentrations were more decreased in HDL3 than in HDL2. Then, the plasmatic concentrations of the main lipoprotein particles present in HDL fraction were modified. For example, a significant decrease of Lp A-I: A-II particles was observed and this variation was similar to that of total apo A-I (r = 0.78). On the other hand, the concentration of Lp A-I particles was slightly modified, apo C-III concentration was markedly decreased whereas apo E concentration was significantly increased (p less than 0.05); in plasma samples obtained 10 days after a severe head injury, apo E reached three times the normal value. PMID- 2930020 TI - [Identification and determination of sensitivity to antibiotics of 31 clinical strains of Acinetobacter other than A. baumannii]. AB - Precise identification and determination of MICs of clinical isolates of Acinetobacter identified to other species than the hospital species A. baumannii were carried out. On 260 Acinetobacter strains isolated in an hospital over a 6 months period, 31 strains (12 p. cent) were identified to species other than A. baumannii. Among these 31 strains, A. Iwoffii sensu stricto (16 strains) and A. haemolyticus (6 strains) were mostly recovered. Eight glucose oxidizing strains were identified to A. haemolyticus (6 strains), Acinetobacter genospecies 3 (2 strains), and A. Iwoffii sensu stricto (1 strain). Antibiotic susceptibilities of these strains were greater than those commonly observed with A. baumannii strains. PMID- 2930021 TI - Fatal Pasteurella haemolytica pneumonia in bighorn sheep after direct contact with clinically normal domestic sheep. AB - Six Rocky Mountain bighorn sheep were raised in captivity from birth (n = 5) or taken from the wild as a lamb (n = 1). After the bighorn sheep were in captivity for over a year, 6 clinically normal domestic sheep were placed on the 2 ha of pasture on which the bighorn sheep were kept. Nasal swab specimens were obtained from all sheep at the time the domestic sheep were introduced. Pasteurella haemolytica was isolated from swab specimens obtained from 4 of 6 domestic sheep, but not from specimens obtained from the bighorn sheep. All 6 bighorn sheep died of acute hemorrhagic pneumonia after exposure to domestic sheep. Death in the bighorn sheep occurred on days 4, 27, 27, 29, 36, or 71 after initial exposure to domestic sheep. Pasteurella haemolytica was isolated from respiratory tract tissue specimens of all bighorn sheep at the time of death. None of the domestic sheep were clinically ill during the study. At the end of the study, 3 of 6 domestic sheep were euthanatized, and at necropsy, P haemolytica was isolated from 2 of them. The most common serotypes in bighorn and domestic sheep were P haemolytica T-3 and A-2. Other serotypes isolated included P haemolytica A-1, A 9, and A-11 in bighorn sheep and A-1 in domestic sheep. On the basis of results of this study and of other reports, domestic sheep and bighorn sheep should not be managed in proximity to each other because of the potential fatal consequences in bighorn sheep. PMID- 2930022 TI - Role of IgE in the pathogenesis of bovine respiratory syncytial virus in sequential infections in vaccinated and nonvaccinated calves. AB - A study was undertaken to evaluate the possible role of IgE in the pathogenesis of bovine respiratory syncytial virus (BRSV) infection. Fifteen calves were allotted at random to 3 treatment groups. One group of 6 calves was vaccinated with attenuated BRSV vaccine before live-virus challenge exposure, another group of 6 was not vaccinated before challenge exposure, and the remaining 3 calves served as controls (nonvaccinated, nonchallenge exposed). Calves of the 2 experimental groups were exposed to 2 live-virus aerosolizations (challenge exposure) 35 days apart. Histamine and BRSV-specific IgE (BRSV-IgE) concentrations in serum, lung lavage fluid, and nasopharyngeal exudate, as well as clinical signs of disease, were evaluated for 14 days after each challenge exposure. Vaccination before challenge exposure with live BRSV appeared to have little or no effect on the severity of the disease, but did appear to affect disease persistence. A correlation (P less than 0.02) existed between signs of disease and BRSV-IgE concentration measured in lung lavage fluid, but this was only true for vaccinated calves. Although no other correlations were found between clinical signs of disease and IgE concentration, analysis of the results additionally revealed a strong correlation (P less than 0.002) between disease signs and histamine concentration in nasopharyngeal exudate from calves of both experimental groups. Thus, indirect evidence implicated IgE in BRSV infection pathogenesis. PMID- 2930023 TI - Cerebrospinal fluid analysis of rabid and vaccinia-rabies glycoprotein recombinant, orally vaccinated raccoons (Procyon lotor). AB - Cerebrospinal fluid obtained from clinically normal free-ranging raccoons was analyzed and compared with CSF obtained from raccoons vaccinated orally with vaccinia-rabies glycoprotein (V-RG) recombinant virus vaccine and subsequently challenged peripherally with street rabies virus, and CSF from naive, rabies virus challenge-exposed control raccoons. Significant differences were not found in CSF of free-ranging or V-RG recombinant virus vaccine recipient raccoons, and there was no evidence of CNS invasion by V-RG virus. The CSF of naive, rabies challenge-exposed control raccoons contained high numbers of lymphocytes and monocytes, compatible with rabies virus encephalitis. Although V-RG orally vaccinated challenge-exposed raccoons were protected from lethal rabies virus infection, a mild lymphocytic pleocytosis was evident at 90 days after challenge exposure. PMID- 2930024 TI - Myoelectric activity of the cecum and right ventral colon in female ponies. AB - The myoelectric activity of the cecum and right ventral colon (RVC) was studied in 4 female ponies. Eight, bipolar Ag-AgCl electrodes were sequentially placed on the seromuscular layer of the cecum (6 electrodes) and RVC (2 electrodes), and recordings were begun 14 days after surgery. The myoelectric activity for each pony was recorded during 12, 60-minute recording sessions done during the interdigestive period (3 to 7 hours after the morning feeding). Coordinated series of spike bursts were recognized as independent motility patterns in the cecum and in the RVC. Local haustra-haustra myoelectric activity involving approximately 40 cm of the cecal body (0.45 +/- 0.03 spike bursts/min) were detected. A series of spike bursts started at the cecal apex and progressed to, but stopped at, the caudal cecal base (0.40 +/- 0.03 spike bursts/min). Infrequently, a series of spike bursts started at the apex and progressed to the cranial cecal base (0.09 +/- 0.01 spike bursts/min). More commonly, a series of spike bursts with a conduction velocity of 3.8 +/- 0.07 cm/s, began in the cranial base and progressed orally to the cecal apex (0.46 +/- 0.03 spike bursts/min). Spike bursts conducted aborally (propulsion) beginning at the origin of the RVC (0.05 +/- 0.007 spike bursts/min) and spike bursts conducted orally (retropulsion; 0.15 +/- 0.02 spike bursts/min) were seen independent of cecal myoelectric activity. A progressive series of coordinated spike bursts, which began at the cecal apex, were conducted through the cecolic orifice and continued into the RVC (0.42 +/- 0.02 spike bursts/min), representing the only pattern common to the cecum and RVC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2930025 TI - Effects of ischemia and dimethyl sulfoxide on equine jejunal vascular resistance, oxygen consumption, intraluminal pressure, and potassium loss. AB - Physiologic effects of 1 hour of ischemia and 1 hour of reperfusion on equine jejunum and protective effects of systemic administration of dimethyl sulfoxide (DMSO, 1 g/kg of body weight) were investigated in 18 ponies, using neurally intact segments of jejunum perfused at constant flow with heparinized blood. Ponies were allotted to 4 groups: group 1, saline solution administered (control, n = 3); group 2, DMSO administered (DMSO, n = 3); group 3, ischemia induced and saline solution administered (ischemia, n = 6); and group 4, ischemia induced and DMSO administered (ischemia-DMSO, n = 6). Intestinal vascular resistance (R, mm of Hg/ml/min/100 g), oxygen consumption (VO2, ml/min/100 g), frequency and amplitude of rhythmic changes in intraluminal pressure, intestinal compliance (C, ml/mm of Hg), and arteriovenous potassium concentration difference (delta AV [K+], mEq/L) were determined and compared with stable preischemic values within groups. There were no significant changes in any variable in ponies of groups 1 or 2. In ponies of group 3, significant (P less than or equal to 0.05) changes included: an initial increase in R during reperfusion, followed by a decrease to values below preischemic values by 15 minutes of reperfusion; decreased VO2 during the entire reperfusion period; increased amplitude of rhythmic contractions during initial reperfusion; decreased frequency of rhythmic contractions during ischemia; and increased delta AV [K+] during initial reperfusion. Changes in ponies of group 4 were identical to changes in ponies of group 3, with the exception that DMSO administration prevented the decrease in R during reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2930026 TI - Hemolytic anemia and red blood cell metabolic disorder attributable to low phosphorus intake in cows. AB - Hypophosphatemia was induced in 2 cows by reducing phosphorus content in their feed after parturition. Serum inorganic phosphorus (Pi) values decreased to 1 mg/dl within 10 days after parturition; and RBC adenosine 5'-triphosphate (ATP) and reduced glutathione values decreased to 50 and 70% of baseline values, respectively. Methemoglobin concentration was moderately higher than normal. These changes preceded the onset of hemolysis, and anemia progressed with decreases in PCV, hemoglobin concentration, and RBC counts. Serum Pi resumed its normal value when anemia was most severe. This RBC disorder was confirmed to be characteristic of hemolytic anemia in cows resulting from hypophosphatemia. The RBC glycolytic intermediates, total triose phosphate (combined glyceraldehyde-3 phosphate and dihydroxyacetone phosphate content) and fructose-1,6-diphosphate, greatly increased in vivo and in vitro with decreases in serum or plasma Pi and RBC ATP. From our results, we concluded that inadequate Pi in the plasma impairs the function and viability of RBC by hindering the production of ATP via disturbance of reactions at the glyceraldehyde-3-phosphate dehydrogenase step. PMID- 2930027 TI - Effect of clindamycin on factor-VII activity in healthy cats. AB - Four healthy cats were given clindamycin orally in daily doses of 25 or 50 mg/kg of body weight for 6 weeks. Significant change in Factor-VII activity was not found, compared with pretreatment values. In 2 cats tested, toxin produced by Clostridium difficile was not detected in fecal samples obtained before treatment and at 6 weeks after treatment, suggesting that intestinal overgrowth by C difficile did not develop. Results of the study seemed to indicate that orally administered clindamycin does not measurably reduce synthesis of vitamin K dependent clotting factors in healthy cats. PMID- 2930028 TI - Pharmacokinetics of sulfadiazine/trimethoprim in neonatal male calves: effect of age and penetration into cerebrospinal fluid. AB - Sulfadiazine (SDZ)/trimethoprim (TMP; 30 mg of SDZ/TMP/kg of body weight) was given IV to the same 6 male calves at 1, 7, and 42 days of age and to 2 additional calves at 7 days of age. Serum concentrations of SDZ and TMP were best represented by a 2-compartment open model, but in 42-day-old calves, CSF concentrations of both drugs were best represented by a 1-compartment open model with first-order input. Between 1 and 42 days of age, the elimination half-life (t1/2(beta)) of SDZ decreased from 5.7 to 3.6 hours, and total body clearance (CLtot) increased from 1.43 to 1.88 ml/min/kg; the area under the curve (AUC0--- infinity) decreased from 291.5 to 225.4 mg/L.h. The distribution coefficient (Vd(area)/kg of body weight) decreased with age, changing from 0.72 to 0.59 L/kg, between 1 and 42 days of age. Therapeutic concentrations of SDZ in serum (greater than 2 micrograms/ml) were maintained for 24 hours in 1-day-old calves and for about 15 hours in 7- and 42-day-old calves. The elimination rate of TMP increased about 9-fold; t1/2(beta) was 8.4, 2.1, and 0.9 hours, respectively, at 1, 7, and 42 days of age. Other values also reflected an increase in TMP elimination rate with age: CLtot increased from 2.8 to 12 to 28.9 ml/min/kg, k13 increased from 0.336 to 0.654 to 1.664/h and AUC0----infinity decreased from 32.8 to 7.9 to 3.1 mg/L.h, respectively. Therapeutic concentrations (greater than 0.1 microgram/ml) were maintained for 15 hours, 8 hours, and about 6 hours in 1-, 7-, and 42-day old calves, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2930029 TI - Induction of equine postanesthetic myositis after halothane-induced hypotension. AB - Wick catheters were used to measure intracompartmental pressures of the extensor carpi radialis muscles and long heads of the triceps brachii muscles of 7 horses maintained under halothane anesthesia during controlled ventilation. Horses were positioned in left lateral recumbency on a water bed for 4 hours. Using a crossover design, 6 of the 7 horses were subjected to normotensive and hypotensive anesthesia on separate occasions. Hypotension was achieved by increasing the inspired halothane concentration. Hematologic and biochemical measurements were determined at designated intervals before, during, and for 7 days after each anesthetic episode. Under hypotensive conditions, 2 horses developed severe generalized myositis and were euthanatized. Three of the 5 other horses developed swelling of the downside masseter muscle, 4 demonstrated mild extensor deficits of the downside forelimb, and 1 had a severe extensor deficit of the uppermost hind limb. As a group, the hypotensive horses had markedly increased activities of serum enzymes (creatine kinase, aspartate transaminase, and blood lactate) and abnormalities in calcium-phosphorus homeostasis. Lameness or enzyme alterations were not observed in normotensive horses. Although the intracompartmental pressure values were markedly increased in the muscle bellies of the compressed limbs of all horses, there was a statistically significant difference in intracompartmental pressures between the downside or compressed muscle compartments of the extensor carpi radialis of hypotensive and normotensive horses. High concentrations of halothane may predispose anesthetized horses to postanesthetic myositis, even when protective padding is used. Intracompartmental muscle pressure, as measured by the wick catheter, may not be a reliable predictor of equine postanesthetic lameness. PMID- 2930031 TI - Turbinate perimeter ratio as an indicator of conchal atrophy for diagnosis of atrophic rhinitis in pigs. AB - Transverse sections of snouts from 171 cross-bred (principally Yorkshire X American Landrace) pigs were evaluated for evidence of turbinate atrophy by use of conventional (atrophic rhinitis [AR] score) and morphometric methods. Of the 171 pigs, 35 were clinically normal (AR score, 0), 65 had mild AR (AR score, 1), 41 had moderate AR (AR score, 2), and 30 had severe AR (AR score, 3). Turbinate cross-sectional area (TA) and the ratio of TA to nostril cross-sectional area, called turbinate area ratio (TAR), had the lowest correlations (r = 0.24 to 0.55) with conventional AR score. Among clinically normal pigs, TA was greater in older pigs as expected, but the TAR values also were significantly (P less than 0.0001) different between 15-week-old pigs (55 kg) and 22-week-old pigs (100 kg). Turbinate perimeter and turbinate perimeter ratio (TPR) were not influenced by pig age or source. The TPR values were closely correlated with subjective visual AR scores (r = 0.73), with AR scores derived by measuring the space between the ventral portion of the scroll and the floor of the nasal cavity (r = 0.72), and the actual size of this space in millimeters (r = 0.71). Mean TPR values for pigs assigned visual AR scores of 0, 1, 2, or 3 were 1.54, 1.25, 0.97, and 0.73, respectively. The 95% confidence intervals around these mean TPR values were discreet and did not overlap. Turbinate perimeter ratio, therefore, may be a more reliable morphometric measure of atrophic rhinitis and also provides parametric data suitable for quantitative analysis. PMID- 2930030 TI - Hematologic changes induced by intravenous administration of diacetoxyscirpenol in pigs, dogs, and calves. AB - Diacetoxyscirpenol (DAS) was given IV to pigs (0, 0.5, and 1.0 mg/kg of body weight), cattle (0 and 0.5 mg/kg), and dogs (0 and 0.5 mg/kg). Blood was collected and hemograms were done at 0.5-hour intervals for 8 hours. The animals were euthanatized at 8 hours after treatment, and bone marrow samples were taken and examined by light microscopy. Moderate to severe necrosis of bone marrow hematopoietic elements was found in animals given DAS. The sequential increase in the type and number of abnormal cells in the blood suggested a successive destruction of the hematopoietic elements. A marked left shift in the neutrophil population was found in animals given DAS. Metarubricytes and large platelets were found in the blood of animals given DAS. Lymphocytes were replaced with immature cells. Pathologic changes were most severe in the pigs given a dosage of 1.0 mg of DAS/kg. The order of species sensitivity to DAS was pigs greater than dogs much greater than cattle. PMID- 2930032 TI - Arterial supply to the spinal cord of dogs and cats. AB - The blood supply patterns to the spinal cord were examined and compared in 15 dogs and 10 cats by use of dissection and radiographic visualization. The lowest percentages of radicular contributions and the smallest diameter vessels were found in the thoracic part of the spinal cord. The central arteries were fewest in number in the thoracic region and unilaterally or bilaterally supplied the gray matter. The percentage of bilaterally distributed central arteries increased from the cervical to the lumbar regions. The anastomotic plexus on the surface of the spinal cord was found to be most dense in the cervical and lumbar regions. PMID- 2930033 TI - Efficacy of triclabendazole against experimentally induced Fascioloides magna infections in sheep. AB - Efficacy of oral administration of 20 mg of triclabendazole/kg of body weight was evaluated against 12-week Fascioloides magna infections in 12 sheep, each inoculated orally with 250 viable metacercariae. From 6 sheep treated with triclabendazole, 1 immature F magna was recovered, whereas 116 F magna with a mean length of 19 +/- 6.5 mm were recovered from 6 untreated control sheep. Efficacy of triclabendazole was 99.14%. Signs of toxicosis or illness were not observed in the sheep. PMID- 2930034 TI - Gastric emptying of a radionuclide-labeled test meal after surgical correction of gastric dilatation-volvulus in dogs. AB - Gastric emptying of a radionuclide-labeled test meal was studied in 10 dogs that had been treated surgically for gastric dilatation-volvulus and in 10 clinically normal (control) dogs. There were no significant differences between the gastric emptying rates and patterns in treated and in control dogs. Thus, there are no indications that gastric emptying is delayed in dogs that have recovered from gastric dilatation-volvulus, and there is no reason for pyloric surgery in dogs with this condition. PMID- 2930035 TI - Wanted: nurses and other staff. PMID- 2930036 TI - Nurse supply, demand reach all-time high. PMID- 2930037 TI - Controversy on RCT dominates teleconference. PMID- 2930038 TI - ANA expresses concerns about nursing home regs. PMID- 2930039 TI - Close ranks, move ahead, staff nurse urges. PMID- 2930040 TI - Nurses, physicians and hospitals are a team. PMID- 2930041 TI - Nursing shortage: a new stage of activism. PMID- 2930042 TI - RN leaders discuss COAR report and recommendations. PMID- 2930043 TI - ANA fights cap on temporary agency fees. PMID- 2930044 TI - Nurses need to get politically involved. PMID- 2930045 TI - As I see it. COAR: we cannot turn back. PMID- 2930047 TI - Financial support needed for strong ANA. PMID- 2930046 TI - Commission on Organizational Assessment and renewal: summary of COAR report. PMID- 2930048 TI - Well elderly need health and social services. PMID- 2930049 TI - Career parallels history of gerontology. PMID- 2930050 TI - ANA advocates 24-hour RN staffing. PMID- 2930051 TI - Professionalizing the nursing home. PMID- 2930052 TI - Emotion in psychotherapy. AB - The therapeutic process involves many different types of affective phenomena. No single therapeutic perspective has been able to encompass within its own theoretical framework all the ways in which emotion plays a role in therapeutic change. A comprehensive, constructive theory of emotion helps transcend the differences in the therapeutic schools by viewing emotion as a complex synthesis of expressive motor, schematic, and conceptual information that provides organisms with information about their responses to situations that helps them orient adaptively in the environment. In addition to improved theory, increased precision in the assessment of affective functioning in therapy, as well as greater specification of different emotional change processes and means of facilitating these, will allow the role of emotion in change to be studied more effectively. A number of different change processes involving emotion are discussed, as well as principles of emotionally focused intervention that help access emotion and promote emotional restructuring. PMID- 2930053 TI - Sex bias and POD. PMID- 2930054 TI - Psychology's contribution to relieving the donor organ shortage: barriers from within. PMID- 2930056 TI - Psychology and self-help groups. Predictions on a partnership. AB - Continued growth and increased legitimacy are anticipated for the American self help group (SHG) phenomenon. Currently estimated at six and a quarter million participants annually, self-help groups will assume a central role in the nation's mental health delivery system over the next two decades. The first part of this article illuminates the self-help group phenomenon itself. Its scope, characteristics, supporting social climate, and associated research issues are reviewed. The second part is a futuristic examination of its interface with the newly industrializing world of health care. Massive increases in mental health services are predicted, especially via the SHG format. Theory development, research sophistication, changing SHG formats, a place in public policy, and acceptance into graduate curricula are also expected, as are collaborative relationships with a variety of professional disciplines. Psychologists are urged to enhance the relevance of the profession by taking an early leadership role in these developments. PMID- 2930055 TI - Women and AIDS-related concerns. Roles for psychologists in helping the worried well. AB - Acquired Immunodeficiency Syndrome (AIDS) has important implications for the practice of psychology. As the epidemic continues, the role of behavior change and psychosocial factors in the spread and transmission of Human Immunodeficiency Virus (HIV) infections assumes increasing significance. Psychologists, as behavior change experts, have a special and challenging role to play in educating the public, particularly women, about AIDS. This article examines AIDS- and HIV related concerns in women with a focus on the personal dilemmas for the practicing psychologist, problems in health behavior advocacy, and methods and pitfalls in modifying sexual behaviors. PMID- 2930057 TI - Building bridges. Psychologists and families of the mentally ill. PMID- 2930059 TI - Schizophrenia as a brain disease. Implications for psychologists and families. PMID- 2930058 TI - The mental health movement in the United States. PMID- 2930061 TI - Neutrophil accumulation and structural changes in nonpulmonary organs after acute lung injury induced by phorbol myristate acetate. AB - Multiple nonpulmonary organ failure contributes significantly to the high mortality rate associated with the adult respiratory distress syndrome (ARDS). However, little is known about specific structural and/or functional alterations that occur in nonpulmonary organs in this syndrome. Therefore, the present study was designed to test the hypothesis that inflammatory cell infiltration and structural changes occur both in the lungs and in nonpulmonary organs in ARDS. To test this hypothesis, neutrophil accumulation and structural alterations were evaluated in nonpulmonary organs from dogs with acute lung injury produced by intravenous phorbol myristate acetate (PMA) (30 micrograms/kg; n = 5). As expected, morphologic changes were present in the lungs of the PMA-treated animals and included a diffuse neutrophilic pneumonitis with interstitial, vascular, and alveolar components. PMA-treated dogs had significant increases in neutrophils (expressed as PMN/mm2 tissue section area) compared with those in control animals in the following organs: heart, 14 +/- 3 versus 4 +/- 1; brain, 2.5 +/- 0.3 versus 0.7 +/- 0.3; duodenum, 34 +/- 7 versus 10 +/- 2; liver, 397 +/ 16 versus 103 +/- 12 (p less than 0.025, all comparisons). In addition, severe necrosis and inflammation of vessels, sinusoidal thrombosis, and hepatic necrosis were noted in the liver. Like the changes noted in the lung, hepatic lesions appeared to be vascular in origin and were consistent with lesions produced by the intravascular activation of neutrophils. No microscopic lesions were detected in the brain, kidney, duodenum, and heart. Taken together, the finding of concurrent lung injury, liver injury, and nonpulmonary organ neutrophil accumulation suggests the possibility of a common pathway of injury in this model of ARDS. PMID- 2930060 TI - Progressive lung injury over a one-year period after a single inhalation exposure to beryllium sulfate. AB - The chronic pulmonary toxicity of beryllium sulfate was examined in rats over a 1 yr period after a single, 1-h exposure. Male rats, exposed in a nose-only inhalation chamber to an aerosol of 4.05 micrograms Be/L, were evaluated for lung toxicity by the methods of bronchoalveolar lavage, lung cell kinetics, and histopathologic analysis. Bronchoalveolar lavage activities for alkaline phosphatase (Alk Pase) and acid phosphatase (Ac Pase) were elevated 3 wk after exposure; lactate dehydrogenase (LDH) and Alk Pase activities peaked 3 months after exposure. Histopathologic analysis revealed progressive focal interstitial pneumonitis with a prominent alveolar component of heteromorphic macrophages, neutrophils, and debris. No increase was noted in the overall labeling index in the alveolar cell population at any of the time points sampled. This study demonstrates the effectiveness of bronchoalveolar lavage fluid analysis in monitoring lung damage over a prolonged period and shows that the pulmonary toxicity of beryllium manifests itself as a progressive lesion from a single 1-h inhalation exposure to BeSO4. PMID- 2930062 TI - Intravascular macrophages in pulmonary capillaries of humans. AB - Pulmonary intravascular macrophages reside in the pulmonary capillaries and phagocytize bacteria and particulates. These cells are prominent in several animals species, but they have not been described in humans. Samples of lung tissue from patients undergoing thoracotomies for excision of noninfectious diseases were examined with transmission electron microscopy to determine if pulmonary intravascular macrophages are present in humans. The macrophages, with cytoplasm closely adjacent to the capillary and with an irregular contour, were seen in specimens from all patients. The morphologic features of human pulmonary intravascular macrophages resemble the appearance of these cells in animals. The potential significance of pulmonary intravascular macrophages is discussed with regard to sepsis-induced acute respiratory failure. PMID- 2930063 TI - Improvement in alveolar macrophage migration after therapeutic whole lung lavage in pulmonary alveolar proteinosis. AB - Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by the accumulation of lipoproteinaceous material in the alveolar space. Alveolar macrophages (AM) in this disease have been noted in the past to have abnormally decreased function. It is not known whether these abnormalities are reversible with treatment of the disease. In this study, the effect of therapeutic whole lung lavage (WLL) on AM migration in four patients with PAP was determined. Standard segmental bronchoalveolar lavage (BAL) was performed 1 day before and 6 days after WLL. AM recovered by BAL were assayed for migratory response to N formyl-methionyl phenylalanine (FMP) and endotoxin-activated human serum (EAHS). As expected, migration toward both stimuli was decreased before WLL compared to a group of normal controls. After WLL, AM migration toward both stimuli was not only greater than before the WLL but also was greater than normal. In one patient, serial BAL over a period of 18 months showed a marked decline in AM migration coincident with a clinical relapse of the disease. Thus, the defect in AM function found in PAP is reversible with WLL but can recur if clinical remission is not sustained. PMID- 2930064 TI - Correlations among naturally occurring resistances to antituberculosis drugs in Mycobacterium avium complex strains. AB - In Mycobacterium avium complex strains, which were not exposed previously to any antituberculosis drugs, resistances to rifampin, minocycline, and kitasamycin, and resistances to streptomycin and kanamycin appeared frequently in the same strains. These data indicate that patterns of drug resistance in these organisms are not random but occur through linked mechanisms. PMID- 2930065 TI - To treat or not to treat, that was the question. PMID- 2930066 TI - Smear- and culture-negative pulmonary tuberculosis: four-month short-course chemotherapy. AB - Patients with positive tuberculin reaction, abnormal chest radiograph, and negative bacteriology are often treated empirically for tuberculosis (TB) after exclusion of other causes. Therapy generally consists of two bactericidal drugs (rifampin [RIF] and isoniazid [INH]) for 9 months or INH for 9 to 12 months. With such a small bacillary population, even less therapy might suffice. Thus we began in January 1980 to discontinue therapy at 4 months when there was sufficient evidence of a paucity of bacilli demonstrated by at least three negative smears and cultures for TB at the start of therapy. To date, 452 such patients have been so treated. Radiographic abnormalities included pulmonary infiltration of varying extent, pleural residuals, and hilar adenopathy. The full course of therapy could not be completed in 38 (8.4%) patients due to death, relocation, or drug toxicity. Side effects of the drugs occurred in 21 (4.7%) patients, but toxic hepatitis occurred in only four (0.9%) patients. Thus, 414 patients completed the full 4-month course of therapy. Of these, 126 (30.4%) patients showed radiographic and/or clinical response suggesting active infection. The remainder showed no such improvement, suggesting either a mistake in diagnosis or dormant TB. During follow-up of the 414 patients from 6 to 78 months (median, 44 months), five (1.2%) patients relapsed: three among responders and two among nonresponders. Thus, among persons suspected of having TB but with negative bacteriology, 4 months of chemotherapy with INH and RIF gave results comparable to those achieved with 9 months of therapy in smear- and culture-positive cases. PMID- 2930067 TI - Nosocomial pneumonia in patients receiving continuous mechanical ventilation. Prospective analysis of 52 episodes with use of a protected specimen brush and quantitative culture techniques. AB - Epidemiologic studies of nosocomial bacterial pneumonia in patients requiring mechanical ventilation have been limited because of the poor reliability of diagnosis procedures in this setting. To determine prognostic and descriptive factors of ventilator-associated (V-A) pneumonia, we prospectively studied 567 patients who had been receiving mechanical ventilation for more than 3 days in our unit. Fiberoptic bronchoscopy using a protected specimen brush (PSB) was performed on each patient suspected of having pneumonia because of the presence of a new pulmonary infiltrate and purulent tracheal secretions. The diagnosis of V-A pneumonia was retained only if PSB specimens yielded greater than 10(3) cfu/ml of at least one microorganism, unless this result was established to be a false positive result on follow-up. V-A pneumonia developed in 49 patients for a total of 52 episodes (9%). The actuarial risk of V-A pneumonia was 6.5% at 10 days, 19% at 20 days, and 28% at 30 days of ventilation. Patients with pneumonia were significantly older (65 versus 57 yr of age, p less than 0.01) and more frequently had severe underlying illnesses (24 versus 10%, p less than 0.01) than did patients without pneumonia. A total of 84 microorganisms (51 gram-negative and 33 gram-positive) were isolated in significant concentrations from PSB specimens. Pseudomonas aeruginosa and Staphylococcus aureus were involved in 31 and 33% of these pneumonias, respectively. Forty percent of all specimens yielded a polymicrobial flora with more than one potential pathogen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2930069 TI - Effect of calcium antagonist gallopamil on antigen-induced early and late bronchoconstrictor responses in allergic sheep. AB - Calcium channel blockers have been shown to modify acute antigen-induced bronchoconstriction in allergic animals and in some human subjects with bronchial asthma; however, the effects of calcium antagonists on late-phase bronchial responses are not known. In this investigation, we studied the effects of calcium antagonist gallopamil on antigen-induced early- and late-phase bronchial responses in sheep allergic to Ascaris suum antigen. In 11 unsedated sheep, specific lung resistance (SRL) was measured before, immediately after, and serially up to 8 h after inhalation challenge with A. suum antigen. On different experiment days, at least 3 wk apart, the sheep were pretreated with gallopamil, administered either as an aerosol (5 mg, n = 10; 10 mg, n = 9) or as an intravenous injection (20 micrograms/kg, n = 10), and the antigen challenge was repeated. For the control experiments (n = 11), mean +/- SE SRL increased immediately after antigen challenge (early response) to 533 +/- 72% of baseline and again 6 to 8 h after challenge (late response) to 304 +/- 31% of baseline (p less than 0.05). Neither intravenously administered nor aerosolized gallopamil had a significant effect on baseline SRL. Both aerosolized and intravenously administered gallopamil blunted the early response and completely blocked the late-phase bronchoconstrictor response (p less than 0.05). Mean SRL during early phase increased to 208 +/- 39% and 245 +/- 39% of baseline with 5 mg and 10 mg of aerosolized gallopamil and to 191 +/- 35% of baseline with intravenously administered gallopamil, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2930068 TI - Preoperative assessment as a predictor of mortality and morbidity after lung resection. AB - To refine the functional guidelines for operability for lung resection, we prospectively studied 55 consecutive patients with suspected lung malignancy thought to be surgically resectable. Lung function and exercise capacity were measured preoperatively and at 3 and 12 months postoperatively. Preoperative pulmonary scintigraphy was used to calculate the contribution to overall function by the affected lung or lobe and to predict postoperative lung function. Pneumonectomy was performed in 18 patients, lobectomy in 29, and thoracotomy without resection in six. No surgery was attempted in two patients who were considered functionally inoperable. Cardiopulmonary complications developed in 16 patients within 30 days of surgery, including three deaths. The predictions of postoperative function correlated well with the measured values at 3 months. For FEV1, r = 0.51 in pneumonectomy (p less than 0.05) and 0.89 in lobectomy (p less than 0.001). Predicted postoperative FEV1 (FEV1-ppo), diffusing capacity (DLCO), predicted postoperative DLCO (DLCO-ppo) and exercise-induced arterial O2 desaturation (delta SaO2) were predictive of postoperative complications including death and respiratory failure. In patients who underwent pneumonectomy, the best predictor of death was FEV1-ppo. The predictions were enhanced by expressing the value as a percentage of the predicted normal value (% pred) rather than in absolute units. For the entire surgical group a FEV1-ppo greater than or equal to 40% pred was associated with no postoperative mortality (n = 47), whereas a value less than 40% pred was associated with a 50% mortality (n = 6), suggesting that resection is feasible when FEV1-ppo is greater than or equal to 40% pred.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2930070 TI - Total respiratory resistance and reactance as a measurement of response to bronchial challenge with histamine. AB - The potential of the forced oscillation technique to detect the airway response on histamine bronchial challenge tests was compared with that of FEV1 and plethysmographic SGaw. In 53 subjects with a history of episodic wheezing and a normal baseline airway resistance, we carried out bronchial challenges with successively doubling concentrations of histamine until FEV1 had dropped by 15% or more or a concentration of 16 mg/ml histamine was reached. For the baseline values, a mean within-subject coefficient of variation was found of 2.8% for FEV1, 7.4% for SGaw, 8.7% for the oscillatory respiratory conductance at 6 Hz (1/Rrs6), and 7.7% for the mean oscillatory respiratory conductance (between 2 and 26 Hz) (1/Rrs). The latter coefficients allow the calculation of the following threshold values: PD15FEV1, PD40SGaw, PD47 1/Rrs6, and PD42 1/Rrs. The probability of exceeding these levels by chance is virtually zero. Histamine challenge caused significant absolute changes in Rrs at 6 Hz (Rrs6), in mean level of Rrs and of respiratory reactance (Xrs), in slope of Rrs and Xrs versus frequency, and in mean curvature of Rrs-frequency curve. A multivariate analysis of the differences between prechallenge and postchallenge values showed that the parameters with the best sensitivity to detect the effect of histamine were, in decreasing order: the relative change of SGaw, of 1/Rrs6, of 1/Rrs, of FEV1, of FVC, and of 1/Vtg, followed by the absolute change of Xrs and of the average slope of the Rrs-frequency relationship.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2930071 TI - Buspirone, an anxiolytic drug that stimulates respiration. AB - The recently released drug buspirone is an anxiolytic agent that appears not to have the sedating effects of barbiturates and benzodiazepines, both known to have respiratory depressant effects. Because of its increasing clinical use, we desired to study the effects of buspirone on respiratory control. We therefore determined central neural respiratory responses, measured from phrenic nerve activity, after intravenous administration in paralyzed, vagotomized, and glomectomized cats whose end-tidal PCO2 and body temperature were kept constant. The responses were compared to the effects of the sedating tranquilizer diazepam. Buspirone had a dose-dependent stimulatory effect on respiratory output primarily through an increase of tidal activity but with an increase of frequency in some animals. Associated with this was a shift of the apneic threshold to a lower level of PCO2 without a change of slope or shape of the CO2 response curve. In contrast, diazepam led to a depression of respiration and a shift of the apneic threshold to a higher PCO2. The findings indicate that buspirone does not have the typical neural respiratory depressant actions of diazepam but instead stimulates respiration. Although the findings will need to be shown to apply to human beings, they suggest that buspirone may be a useful drug to treat anxiety in patients without causing undesirable respiratory depression. PMID- 2930072 TI - Characteristics of normal lung sounds after adaptive filtering. AB - Lung sounds were recorded from five normal male subjects during tidal breathing. Simultaneous electrocardiograms were recorded and used as index signals to generate simulated heart sounds for digital subtraction from recorded lung sounds to obtain purer lung sounds. Five random breaths from each subject were analyzed. Sound signals were band-pass filtered 25 to 1,000 Hz (antialiasing), digitized at 3,000 Hz, and then subjected to (1) direct fast Fourier transform (FFT) without filtering (NF); (2) digital high-pass filtering at 75 Hz and subsequent FFT (75 HzF); (3) adaptive filtering and subsequent FFT (AF). The FFT algorithms of all lung sounds were characterized by mean, median, and mode frequencies. The mean, median, and mode of NF were lower than those of 75 HzF (64.98 +/- 4.04 versus 150.42 +/- 17.49, mean +/- SE, p less than 0.003; 44.57 +/- 2.06 versus 111.81.5.78, p less than 0.0003; 36.81 +/- 1.77 versus 86.16 +/- 3.13, p less than 0.0001) and those of AF (64.98 +/- 4.04 versus 96.87 +/- 11.58, p less than 0.01; 44.57 +/- 2.06 versus 68.23 +/- 10.44, p less than 0.05; 36.81 +/- 1.78 versus 52.24 +/- 8.97, p less than 0.06). The mean, median, and mode of AF were lower than those of 75 HzF (96.87 +/- 11.58 versus 150.42 +/- 17.49, p less than 0.02; 68.23 +/- 10.44 versus 111.81 +/- 5.77, p less than 0.007; 52.24 +/- 8.97 versus 86.16 +/- 3.73, p less than 0.01). The results indicated that by filtering out low frequency heart sounds, the frequency spectrum of lung sounds was moved upward.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2930073 TI - Flow-volume curves in snoring patients with and without obstructive sleep apnea. AB - To examine the usefulness of flow-volume curves as a screening test for the diagnosis of obstructive sleep apnea (OSA), we studied 405 consecutive patients referred for evaluation of possible OSA. All patients had full pulmonary function studies, which included measurements of maximal inspiratory and expiratory flow volume curves, and nocturnal polysomnography, including continuous monitoring of snoring sounds. When the results were analyzed, of the 405 patients studied, 207 had OSA (apnea/hypopnea index [AHI] greater than 10) and 198 did not. Flow-volume curves were examined for the presence of upper airway obstruction defined as midvital capacity flow ratio (MVCFR = ratio of the maximal expiratory flow at 50% of vital capacity to maximal inspiratory flow at 50% of vital capacity) greater than 1.0. We found no significant difference in the values of MVCFR between the two groups: MVCFR was equal to 0.69 +/- 0.31 for nonapneic snorers, and 0.68 +/- 0.29 for the apneic snorers. Furthermore, we redefined the apneic and nonapneic groups using different cutoff values of AHI: 20, 30, 40, and 50. Independently of the AHI cutoff used, we found no significant difference in the MVCFR between the two groups. Linear regression analysis for the entire group of 405 patients revealed no significant correlation between MVCFR and the AHI or the snoring indices. We calculated the sensitivity, specificity, and predictive values of MVCFR for the diagnosis of OSA. We found that this test had 12% sensitivity, 86% specificity, 47% positive predictive value, and 46% negative predictive value.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2930074 TI - Mechanical loads on the ventilatory muscles. A theoretical analysis. AB - Two indices of the total mechanical load on the ventilatory muscles, i.e., the work per minute (W.min-1) and the inflation pressure time index (PTI), have been developed to better assess muscle energy demands and fatigue potential. However, the relationship of these two indices to the various individual determinants of load and to muscle energy demands and fatigue potential are not well understood. To investigate these relationships in a theoretical fashion, we first constructed a computer model to quantitate the magnitude and relative effects of changes in the ventilation component of load, i.e., alveolar ventilation demands (VA) and dead space volume (VD), and changes in the respiratory system impedance component of load, i.e., compliance (Crs) and resistance (Raw), on W.min-1 and PTI over a wide, clinically relevant, range of ventilatory conditions. From this analysis, we demonstrated that: (1) high mechanical loads could be developed over a wide range of circumstances (i.e., W.min-1 ranged from 0.29 kg.m.min-1 to 30.55 kg.m.min-1 and PTI ranged from 1.22 to 28.8 cm H2O as ventilation increased from 7 to 39 L.min-1 and impedances worsened from normal to a combined restricted and obstructed pattern); (2) each load determinant (i.e., VA, VD, Crs, and Raw) contributed substantially to these two indices of total mechanical load; (3) although impedance changes had comparable effects on W.min-1 and PTI, ventilation changes, as would be expected, had a greater effect on W.min-1 than on PTI.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2930075 TI - Limitations of computed tomography in the assessment of emphysema. AB - Thirty-eight patients undergoing lobectomy or pneumonectomy for carcinoma had preoperative computed tomography (CT) of the chest. Twenty-seven had both 1.5 mm and 10 mm collimation scans, and eleven had 10 mm collimation images only. These images were analyzed for the extent and severity of emphysema, and the analysis compared to the pathologic findings in the corresponding transverse slice of lung. The latter was graded by a modification of a panel of standards and by a grid system numerically expressing extent and severity. The grid system is theoretically superior to the panel of standards because it allows better quantitation of early emphysema and, contrary to the set of standards, is designed to analyze transverse CT images and corresponding pathologic slices. There was good correlation between the CT score and the pathologic score using the panel of standards (r = 0.81, p less than 0.001) but a lower correlation with the grid system (r = 0.70, p less than 0.001). The correlation improved slightly with 1.5 as compared to 10 mm collimation scans. Close comparison between the CT and grid scores showed that CT was sensitive in demonstrating early distal acinar and irregular emphysema. However, CT consistently underestimated the extent of centriacinar and panacinar emphysema because most lesions less than 0.5 cm in diameter were missed. We conclude that CT is insensitive in detecting the earliest lesions of emphysema. PMID- 2930076 TI - Raja pleural biopsy needle. A comparison with the Abrams needle in experimental pleural effusion. AB - The Raja pleural biopsy needle, 3 mm in external diameter and fitted with a titanium alloy biopsy flap, was compared with the Abrams needle in six dogs with experimentally induced pleural effusion. One hundred twenty-four pleural biopsies were performed using either the Raja needle or the Abrams needle (62 with each needle). No complication occurred with either needle. The Raja pleural biopsy needle yielded a statistically significant larger pleural tissue specimen with a statistically significant lower frequency of crush artifacts. The size of the pleura obtained by the Abrams needle averaged 4,401 +/- 559 microns2 (mean +/- SE) compared with 8,652 +/- 1,099 microns2 with the Raja needle (p less than 0.01; Student two-tailed t test). Biopsies by the Abrams needle showed crush artifacts in 25.8% of the specimens, whereas 8.06% of biopsies with the Raja needle showed crush artifacts (p less than 0.02; Fisher's two-tailed exact test). In conclusion, the Raja pleural biopsy needle is safe to use and, despite its smaller diameter (3mm versus 4mm external diameter of the Abrams needle), yields significantly larger and less frequently distorted pleural specimens. PMID- 2930077 TI - Long-term pulmonary sequelae after Legionella pneumophila infection in the hamster. AB - It has been reported that infections with Legionella pneumophila can lead to chronic inflammatory and fibrotic reactions in the human lung. To better characterize the nature of the residual abnormalities caused by this bacterium, we inoculated Syrian hamsters intratracheally with 10(8) serotype 1 L. pneumophila organisms and assessed histologic, functional, and biochemical changes at intervals up to 180 days. Acutely, L. pneumophila caused an intense alveolar macrophage (AM) and polymorphonuclear leukocyte (PMN) response within the lower air spaces, air-filled lungs were noncompliant, and there was an associated 25 to 50% increase in the lung content of collagen and elastin after 10 days. An inflammatory response, consisting principally of AM and centered around the terminal bronchioles, was still prominent in some infected lungs after 90 and 180 days, and the severity of the inflammation was correlated with a persistent restrictive defect in the elastic behavior of the lung. However, by histologic examination, fibrosis was not prominent, and the more representative abnormality was one of mild, diffuse air-space enlargement. Frank emphysematous changes were present focally in some lungs. In addition, an irregularly distributed lymphocytic infiltrate and goblet cell metaplasia were present in the larger bronchi of infected animals. We conclude that a single infection with L. pneumophila is capable of causing long-term inflammatory reactions in the lung, with morphologic features of both fibrosis and emphysema. PMID- 2930078 TI - Experimental hypersensitivity pneumonitis in guinea pigs. Kinetics and dose response. AB - Experimental hypersensitivity pneumonitis (HP) can be transferred by cells cultured in vitro with antigen, but not by noncultured cells. We determined the relationship between antigen concentration, time of culture, and development of competence to transfer HP and if separation of lymphoblasts from a noncultured cell population would allow transfer. We cultured lymph node cells from sensitized Strain II guinea pigs with a soluble extract of Micropolyspora faeni (10 micrograms/ml) for 48, 72, and 96 h, and isolated and transferred lymphoblasts intravenously to syngeneic recipients. Other animals received lymphoblasts from 72-h cultures exposed to 0, 0.1, 1, 10, or 30 micrograms/ml M. faeni. We also separated and transferred lymphoblasts from noncultured lymph node cell populations. Control animals received equal volumes of media. The animals were challenged intratracheally with M. faeni 48 h after the cell transfer, and they were killed 4 days after intratracheal challenge. Randomly selected microscopic fields of the lung (250/animal) were judged to be normal or abnormal without knowledge of treatment. All guinea pigs were maintained in HEPA-filtered air. There was a low level of pulmonary response to an intratracheal challenge of M. faeni in animals that received media and a substantial increase (p less than 0.01) in the extent of pulmonary abnormalities in the animals receiving lymphoblasts cultured for 72 and 96 but not for 48 h. Recipients of lymphoblasts cultured for 72 h with 1, 10, and 30 but not zero and 0.1 micrograms/ml M. faeni exhibited increased extent of pulmonary abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2930079 TI - American Lung Association, American Thoracic Society, 1989 annual meeting. May 14 17, 1989, Cincinnati, Ohio. Abstracts. PMID- 2930080 TI - [Audiologic evaluation of children by auditory responses of the brainstem]. AB - Brainstem auditory evoked responses (BAER) were recorded in 112 children (0-14 years) submitted to us from a ORL source to evaluate the auditory function. The othologic examination and different audiologic tests (pure tone audiometry, impedance measurement, stapedial reflex) showed no definite results due to several reasons including age, uncooperativeness, low reliability, or communication impairment. The following items were evaluated: 1) Wave V threshold. 2) Latency-intensity function. 3) Interwave timing, I-V amplitude ratio, wave amputation, response to the changing rate of stimulation. Results showed the utility of BAER to: 1) Confirm the audiologic impairment: 2) determine if the anomalies are uni or bilateral; 3) quantify the intensity of hearing loss, and 4) establish a topographic diagnosis of the disease. PMID- 2930081 TI - [Behavior of full-term low-birth weight infants based on the Brazelton scale]. AB - In order to evaluate the specific effects of low birth weight on neonatal behaviour, a group of 41 small-for-dates newborns were assessed using the updated Brazelton's neonatal behavioral assessment scale. Results were compared to those obtained from 41 neonates of full-weight, healthy and of similar characteristics. According to these data behavioral profile of the full-term but underweight newborn in comparison to full-weight newborn, could be described as follows: less reaction to animate and inanimate stimuli: more passivity and indifference to social interaction; poor motor general tone and poor consolability. PMID- 2930082 TI - [Carbamazepine in paroxysmal choreoathetosis in Sydenham's chorea]. AB - There are presented three different forms of chorea, in which we have observed an spectacular response to the administration of carbamazepine. The two first cases are paroxysmal choreoathetosis. Both are free of episodes of choreoathetosis under the administration or very low dosis of carbamazepine. However when a placebo is been used or in an accidental omit of the drug, the crisis reapears. The third case is a Sydenham chorea. It received three months of treatment on a 20 mg/kg dosis, the symptoms dimished on the first week. After a year he has not suffered any relapse. PMID- 2930083 TI - [Survey of the demands on pediatric outpatient consultation clinics in Vigo]. PMID- 2930084 TI - [Fibromuscular dysplasia and Moya-Moya disease]. PMID- 2930085 TI - [Sea-blue histiocyte syndrome associated with chronic hepatitis B and ocular albinism]. PMID- 2930086 TI - [Anuria caused by obstructive lithiasis]. PMID- 2930087 TI - [Amyloid tumor of the trachea. Presentation of a pediatric case]. PMID- 2930088 TI - [Dacryocystitis in early infancy]. PMID- 2930089 TI - [Pulmonary sequestration. Diagnosis of an aberrant blood vessel by CT imaging and bidimensional Doppler echography]. PMID- 2930090 TI - [Nephropathy caused by ventriculo-atrial derivation (shunt nephritis)]. AB - We report three patients (one, nine and ten year old) who suffered from secondary nephritis caused by an infection of a ventriculo-atrial shunt. In all three cases diagnosis was made based on persistent hematuria accompanied by prolonged fever of unclear origin and was subsequently confirmed by the presence of staphylococcus in the blood. LCR and prosthesis cultures and in the renal biopsy. The period of time elapsed between the insertion of the shunt, the beginning of the illness and the diagnosis, was variable. In the three cases, the treatment consisted of removal of the infected shunt and insertion of a new one in the peritoneum together with antibiotic treatment. The outcome was successful in only two cases, the third died. The hystological study showed the presence of: membranoproliferative, proliferative and intra and extra capillary glomerulonephritis with diffuse semilunae in each case. We point out the importance of the prosthesis infection by low virulence germs, the continuous dissemination of these into the circulatory system and the production and depositing of antibodies at the renal level. PMID- 2930091 TI - Chronic aortic insufficiency: factors associated with progression to aortic valve replacement. AB - STUDY OBJECTIVE: To determine whether the initial measurement of clinical variables in patients with chronic stable aortic insufficiency is helpful in identifying patients at risk for earlier progression to aortic valve replacement. DESIGN: Prospective analysis of a cohort of patients for a median follow-up time of 44 months (range, 8 to 57). SETTING: Referral-based cardiology clinics at two university hospitals and their affiliated Veterans Administration medical centers. PATIENTS: Cohort of 50 asymptomatic or minimally symptomatic patients with chronic aortic insufficiency and left ventricular enlargement. Patients had preserved left ventricular ejection fraction at rest and no evidence of coronary artery disease or significant noncardiac illness. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Baseline evaluation included a history and physical examination, chest roentgenogram. M-mode echocardiogram, treadmill test, and radionuclide angiogram done at rest and during supine bicycle exercise. Ten patients progressed to surgery because of the onset of limiting symptoms or objective evidence of left ventricular dysfunction, or both; the overall rate was 4% +/- 3% per year. The Breslow and Mantel-Cox statistics were used to compute survival (surgery-free) dichotomized by prognostic variables. The progression to surgery was earlier in patients with left ventricular end-diastolic volume indices of 150 cc/m2 or more, end-systolic volume indices of 60 cc/m2 or more, a left ventricular ejection fraction at maximal exercise of less than 0.50, or an end-systolic wall stress of 86 dynes/cm2 or more. CONCLUSIONS: Patients at higher and lower risk for early progression to aortic valve replacement can be identified through the measurement of left ventricular size and function. This information can be used to decide the frequency and intensity of follow-up evaluation in these patients. PMID- 2930092 TI - The effect of caffeine on exercise tolerance and left ventricular function in patients with coronary artery disease. AB - STUDY OBJECTIVE: To determine whether acute oral caffeine ingestion by patients with coronary artery disease results in decreased treadmill exercise performance or deterioration of echocardiographic measures of systolic or diastolic left ventricular function. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Referral-based cardiovascular exercise laboratory at an urban teaching hospital. PATIENTS: Thirteen volunteers with clinically stable coronary artery disease who had exercise tests after a 2-week caffeine-free washout period. Patients continued treatment with standard antianginal medications during the study period. INTERVENTIONS: Maximal exercise treadmill testing and exercise echocardiography were done at baseline, after acute ingestion of a placebo beverage (97% caffeine-free coffee), or after drinking an identical beverage containing 250 mg of caffeine sodium benzoate. MEASUREMENTS AND MAIN RESULTS: Acute ingestion of caffeine produced a serum level of 4.50 +/- 0.16 micrograms/mL, but had no effect on resting supine heart rate, blood pressure, left ventricular fractional shortening, posterior left ventricular wall thinning or peak rates of increase in left ventricular diastolic dimension. Despite a small increase in peak systolic blood pressure during exercise (baseline, 153 +/- 8; placebo, 154 +/- 8; caffeine, 161 +/- 7 mm Hg; P less than 0.05), exercise duration, time to onset of angina, and time to 0.1 mV ST depression did not differ after ingestion of placebo or caffeine. Rate-pressure product at onset of angina and onset of 0.1 mV of ST depression were also unchanged. In response to exercise, echocardiographic measures of left ventricular systolic and diastolic function were unchanged after caffeine compared with placebo ingestion. CONCLUSIONS: These data suggest that patients with exercise-induced ischemia who are receiving appropriate antianginal therapy tolerate the caffeine-equivalent of three cups of coffee without detrimental effect on intensity of ischemia, myocardial function, or exercise duration. PMID- 2930093 TI - Mild cystic fibrosis in a consanguineous family. AB - Cystic fibrosis is an autosomal recessive genetic disorder linked to chromosome 7q in all families studied. Expression of the disease varies, but the genetic basis for clinical heterogeneity is unknown. We describe an extended consanguineous family with pulmonary disease and the sweat gland phenotype of cystic fibrosis. In the members of this family, clinical expression of the disease was mild, as manifested by the absence of severe childhood lung disease and increased longevity with better functional status than that expected for age. The degree of pancreatic exocrine insufficiency varied (4/10), but the older patients had normal pancreatic function. The pedigree suggested the likelihood of common ancestry, and eight of the ten affected persons were clearly related. At least three of the family members with the mildest clinical disease had consanguineous parents and may therefore have been homozygous for a variant cystic fibrosis gene. The mild expression of cystic fibrosis in this family provides evidence for a form of cystic fibrosis that is intrinsically less debilitating than the classic form. PMID- 2930094 TI - Training physicians in counseling about smoking cessation. A randomized trial of the "Quit for Life" program. AB - STUDY OBJECTIVE: To test whether physicians who receive a continuing education program ("Quit for Life") about how to counsel smokers to quit would counsel smokers more effectively and have higher rates of long-term smoking cessation among their patients who smoke. DESIGN: Randomized trial with blinded assessment of principal outcomes. SETTING: Four health maintenance organization medical centers in northern California. SUBJECTS: Eighty-one internists assigned by blinded randomization to receive training (40) or serve as controls (41). Consecutive samples of smokers visiting each physician (mean, 25.6 patients per experimental and 25.2 per control physician). INTERVENTIONS: Internists received 3 hours of training about how to help smokers quit. Physicians and their office staff also were given self-help booklets to distribute free to smokers and were urged to use a system of stickers on charts to remind physicians to counsel smokers about quitting. MEASUREMENTS AND MAIN RESULTS: On the basis of telephone interviews with patients after visiting the physician, we determined that internists who attended the Quit for Life program discussed smoking with more patients who smoked, spent more time counseling them about smoking, helped more patients set dates to quit smoking, gave out more self-help booklets, and made more follow-up appointments to discuss smoking than did internists in the control group. One year later, the rate of biochemically confirmed, long-term (greater than or equal to 9 months) abstinence from smoking was 1% higher among all patients of trained internists than among patients of controls (95% CI, -0.1% to +2.3%), and 2.2% (+0.2% to +4.3%) higher among the patients who most wanted to quit smoking. CONCLUSIONS: This continuing education program substantially changed the way physicians counseled smokers. As a result, a few more patients who wanted to quit smoking achieved long-term abstinence. PMID- 2930096 TI - Working conditions and supervision for residents in internal medicine programs: recommendations. American College of Physicians. AB - Changes intended to improve resident working conditions and supervision must take into account the complex realities governing teaching services. The American College of Physicians supports the ongoing reexamination of these issues, and recommends the following: 1) change be systematic and coordinated, balancing patient care and teaching needs; 2) changes in the medical care system itself are necessary in this process; 3) efforts be continued to reduce preventable medical error on teaching services within the limits of uncertainty intrinsic to medical practice; 4) reasonable restriction be placed on total continuous duty hours, but residents not disengage themselves prematurely from care of their patients; 5) residency training specifically teach techniques for balancing patient service, education, and personal life; 6) the issue of resident workload be addressed; and 7) formal evaluation of supervisory competence, explicit attention to the spirit of resident-supervisor relationships, respect for the principle of meaningful patient responsibility, and formal resident credentialing all be taken into account in improving resident supervision. PMID- 2930095 TI - Encouraging primary care physicians to help smokers quit. A randomized, controlled trial. AB - STUDY OBJECTIVE: To increase the effect that primary care physicians have on their patients who smoke. DESIGN: Randomized, controlled trial with 112 general internists and their patients who smoke. PATIENTS: Sample of 1420 patients from a general medicine clinic of a city-county teaching hospital, who smoke at least one cigarette a day and were recruited regardless of their interest in quitting smoking. INTERVENTIONS: Physicians were randomly assigned to one of four groups: participants who received a protocol for smoking management and a lecture on the consequences and management of smoking (control); in addition, had nicotine gum freely available to patients (gum); had stickers attached to their smokers' charts (reminder); or had both gum and reminders (both). MEASUREMENTS AND MAIN RESULTS: The percentage of patients with a return visit at 6 months who quit smoking (alveolar carbon monoxide of less than nine parts per million) was 1.3% (control), 7.7% (gum), 7.0% (reminders), and 6.3% (both). At 1 year the percentages were 2.7%, 8.8%, 15.0%, and 9.6%, respectively. Subsequent pairwise comparisons showed that the three intervention groups were not significantly different, but that each was significantly different from the control group (P less than 0.05). Physicians in all three intervention groups spent significantly more time than did the physicians in the control group counseling their patients about smoking. CONCLUSIONS: The availability of nicotine gum or labeling the charts of smokers can help primary care physicians increase their success rates two- to six-fold in helping patients quit smoking. If all primary care physicians used these procedures, they could help an additional 2 million smokers quit. PMID- 2930097 TI - Chronic lymphocytic leukemia: recommendations. PMID- 2930098 TI - Amyloidosis, diarrhea, and a somatostatin analogue. PMID- 2930099 TI - Oral lichen planus and hepatic cirrhosis. PMID- 2930100 TI - Tumor necrosis factor and obesity. PMID- 2930102 TI - Diagnostic assessment of dementia. PMID- 2930101 TI - Thyrotoxicosis, cryofibrinogenemia, Sinutab Maximum Strength, and purple ears. PMID- 2930103 TI - Information for the physician. PMID- 2930104 TI - Earlier diagnosis of human immunodeficiency virus (HIV) infection and more counseling. PMID- 2930105 TI - Internal medicine in the National Resident Matching Program 1978-1989. PMID- 2930106 TI - A common-source outbreak of fulminant hepatitis B in a hospital. AB - A nosocomial outbreak of fulminant hepatitis B infection at a medical center in Haifa, Israel, between 7 and 26 June 1986, involved five patients who had been hospitalized previously in the medical ward in late April and early May (first generation). This outbreak had an unusual clinical course, with fulminant hepatic failure associated with acute renal failure from acute glomerulonephritis, leading to death within a few days. The onset dates of hepatitis were tightly clustered temporally and incubation periods were short. Extensive laboratory and epidemiologic evaluation showed that the probable common-source vehicle of transmission was a multiple-dose vial of heparin and normal saline flush solution that may have been contaminated by blood of a known HBsAg carrier, who was positive for anti-HBe, hospitalized at the same time. A sixth patient died in August 1986 (second generation), after his initial admission in June that coincided with the terminal hospitalizations of three first-generation patients. Those patients had marked coagulopathies, and transmission to the sixth patient most probably occurred through environmental contamination by patients or through cross-contamination between patients through staff. The unusually high mortality rate (5 of 6) in this outbreak has not been definitely explained. PMID- 2930107 TI - Systemic gas embolism complicating mechanical ventilation in the adult respiratory distress syndrome. AB - Most forms of barotrauma related to mechanical ventilation are known to occur in both adult and pediatric patients. The pressure-driven transfer of gas from the alveolar compartment to the systemic circulation, a devastating complication of ventilatory support in infants, is not generally recognized as a consequence of ventilatory support in adults. Two young adult patients who received ventilatory support with high levels of positive pressure for pneumonia and the adult respiratory distress syndrome developed massive sub-pleural air cysts, interstitial emphysema, and tension pneumothoraces. Despite receiving appropriate treatment for these problems, the patients had recurrent episodes of cerebral infarction, myocardial injury, and a characteristic pattern of livedo reticularis. This distinctive triad of findings, otherwise unexplained and occurring in the setting of cystic barotrauma, is highly suggestive of systemic gas embolism. Although our patients presented with dramatic clinical features, we believe that patients with ventilator-related gas embolism may present more commonly with subtler signs, such as puzzling disturbances in heart rhythm or mental status, seizure activity, hypotension, localized pain, or other embolic manifestations readily ascribed to other causes in critically ill patients. PMID- 2930108 TI - Evaluation of a serologic marker, CA19-9, in the diagnosis of pancreatic cancer. AB - STUDY OBJECTIVE: To determine the utility of the serologic marker CA19-9 in the diagnosis of pancreatic cancer in patients suspected of having a pancreatic disorder. DESIGN: Blinded study of frozen pedigreed serum samples collected at time of diagnostic evaluation with follow-up review at a mean of 8 years. SETTING: A general university teaching hospital serving both primary and referral patient populations. MEASUREMENTS AND MAIN RESULTS: Sera collected prospectively from 1978 to 1980 from 261 patients undergoing imaging studies of the pancreas (ultrasound, computed tomography, endoscopic retrograde cholangiopancreatography) for a variety of symptoms were assayed for CA19-9 levels, and the results were compared with earlier determinations of other potential markers for pancreatic cancer. In 54 patients ultimately shown to have pancreatic cancer, the CA19-9 assay showed a sensitivity of 70% with a median value of 349 u/mL (normal less than 70 u/mL) and range, 7.3 to 2,859,964 u/mL, whereas specificity of the marker in this population was 87%. The positive predictive value was 59%, and the negative predictive value was 92%. Results of CA19-9 testing in the small group of patients with definitive staging information showed no difference in sensitivity between patients with local/regional disease (n = 6) and those with distant metastases (n = 14), 50% compared with 71% (P = 0.613). CONCLUSION: CA19 9 was found to be a more sensitive and specific marker of pancreatic cancer than other serologic markers and should be a useful test in the patient with suspected pancreatic disease. PMID- 2930110 TI - Physical examination of asymptomatic adults for screening. PMID- 2930111 TI - Colonic polyps in asymptomatic patients. PMID- 2930109 TI - Predictive validity of certification by the American Board of Internal Medicine. AB - STUDY OBJECTIVE: To determine the predictive validity of the American Board of Internal Medicine (ABIM) certification process. DESIGN: Prospective measurement of the knowledge, skills, and attitudes of 185 ABIM-certified and 74 noncertified internists by a written examination; evaluation by professional associates; a patient questionnaire assessing satisfaction with care, physician's counseling role, and preventive care; and review of records of patients with common illnesses. SUBJECTS: Practicing internists who completed training or received ABIM certification 5 to 10 years previously. SETTING: Office-based practices in six western states. RESULTS OF DATA ANALYSIS: Physicians certified by the ABIM had significantly higher scores on the written examination than the noncertified physicians, and scores on our examination correlated highly with the ABIM certification examination (r = 0.73). Ratings of clinical skills by professional associates were significantly higher for certified internists and also correlated highly with ABIM examination scores (r = 0.53 to 0.59). Regression analysis showed that ABIM certification status was the major variable affecting performance on these measures of clinical competence. Results from other measures did not show many differences between certified and noncertified physicians in the care of patients with common illnesses, but modest differences in preventive care and a few differences in outcome favored the certified physicians. CONCLUSIONS: Comparison of findings from the written examination and the professional associate ratings with certification status and original ABIM certification examination scores shows predictive validity of ABIM certification. Further studies are needed to determine if certification status predicts important differences in the care of patients with complex illnesses. PMID- 2930113 TI - Lipomas and potassium intake. PMID- 2930112 TI - Right-sided staphylococcal endocarditis. PMID- 2930114 TI - Thiazide-induced hyponatremia and vasopressin release. PMID- 2930115 TI - Norfloxacin and warfarin. PMID- 2930116 TI - The once and future physician. PMID- 2930117 TI - Retinal cotton-wool-like spots: a marker for AIDS? AB - The prognostic value of ocular manifestations and its correlation with immune changes in HIV-infected subjects was studied longitudinally with an average follow-up of one year (3-22 months). The most common ocular manifestations were retinal cotton-wool-like spots, observed in 58.8% of AIDS patients and in 76.9% of those with ocular involvement. Two of three ARC cases with cotton-wool-like spots developed Pneumocystis carinii pneumonia a few weeks after ophthalmoscopic examination. A close correlation between ocular changes and decrease of CD4+ lymphocytes was observed. In our opinion, these ocular manifestations are as useful as opportunistic infections or AIDS-related neoplasias in the natural history of HIV infection. PMID- 2930118 TI - Laser treatment of toxoplasmosis. AB - Medical treatment of toxoplasmosis may not be effective always, or toxicities may preclude further use of medications. In this situation, laser photocoagulation may be considered. Three cases of toxoplasmosis were treated with krypton/argon laser photocoagulation. One case required retreatment. All remained quiescent after treatment. PMID- 2930119 TI - Intraepikeratophakia: surgical technique and postoperative visual recovery. AB - Intraepikeratophakia is a refractive surgical technique useful in the treatment of aphakia, myopia, and keratoconus. It is based on the epikeratophakia technique developed by Kaufman and Werblin and involves the grafting of corneal epithelium onto a donor lenticule. Previous findings noted that grafting of the corneal epithelium results in rapid surgical recovery and increased patient comfort. It also lowers the likelihood of surgical failure (loss of the donor lenticule). The postoperative visual acuity of 42 consecutive patients who underwent either intraepikeratophakia or epikeratophakia is described. Patients who underwent intraepikeratophakia had a significantly faster rate of visual recovery than epikeratophakia patients. Of all patients 88% had a visual acuity of within two Snellen lines of best-corrected preoperative visual acuity by six months postoperatively. Of these 20 of 23 (87%) intraepikeratophakia patients and 17 of 19 (89%) epikeratophakia patients obtained this level of visual recovery. Special instrumentation and a modification of the surgical technique involving the use of tissue culture techniques is presented. Patients undergoing this modification of intraepikeratophakia had the fastest visual recovery. Continued improvements in the methodology of intraepikeratophakia are expected. PMID- 2930120 TI - Leishmania (Viannia) naiffi sp. n., a parasite of the armadillo, Dasypus novemcinctus (L.) in Amazonian Brazil. AB - A new leishmanial parasite, Leishmania (Viannia) naiffi sp. n., is described from the nine-banded armadillo, Dasypus novemcinctus (Edentata: Dasypodidae), from Para State, north Brazil. The parasite grows luxuriantly in Diffco blood-agar medium (B47), but poorly in the skin of intradermally inoculated hamsters. A comparison of isoenzyme profiles by starch gel electrophoresis separates the parasite from L. (V) braziliensis and L. (V.) guyanensis by the enzymes ASAT, ALAT, PGM, GPI, G6PD, PEP, MPI and GD, and from Leishmania (Leishmania) chagasi, L. (L.) amazonensis and L. (L.) deanei by ASAT, ALAT, PGM, GPI, MPI, G6PD, MDH, PEP and ACON. Finally, L. (V.) naiffi is serologically differentiated from L. (V.) braziliensis, L. (V.) guyanensis and L. (V.) panamensis on monoclonal antibodies specific for these parasites. PMID- 2930121 TI - [Description of Cercopithifilaria verveti n. sp., a subcutaneous filaria of a Cercopithecus in Kenya]. AB - Description of the fifth species of Cercopithifilaria from african primates. The four previous species are parasites of baboons (Papio spp.), this one is a parasite of the vervet monkey (cercopithecus aethiops). The male has yet to be recovered for the new species. PMID- 2930122 TI - [Evaluation of coverage under the national plan for measles and rubella vaccination based on a sample of schools]. AB - In order to evaluate the prevalence of immunization against measles and rubella, a survey was performed in children attending randomly selected nursery schools throughout France. School physicians filled in a questionnaire during the visit prior to admission to first grade (5-6 years of age). Parents attend this visit and present their child's immunization card. The survey was carried out in 1979. Prevalence of immunization among surveyed children was 26% for measles and 2% for rubella. These prevalences varied across regions, and according to whether the school was located in an urban or rural area. Sixty-nine per cent of parents were aware of the existence of the vaccine against measles and 12% declared they did not wish their child to receive this vaccine. The main reason for non immunization was failure of the family physician to suggest the vaccine. PMID- 2930123 TI - [Allergy and desensitization to hymenoptera venom in children]. AB - Among 15 children who were stung by hymenoptera, 5 underwent semi-rapid desensitization using the outpatient Molkhou method. This technique was well tolerated; desensitization was stopped when protective IgG levels measured by RIP (radioimmunoprecipitation) reached 50% and skin tests and RASTs became negative. In a comparable series of adults, however, discontinuation of the desensitization was considered only following satisfactory tolerance of an accidental or planned sting. In children, semi-rapid desensitization is very effective and has also been proposed for allergies to air borne allergens such as mites and pollens when increased doses are required to improve protection. PMID- 2930124 TI - [Etiology of childhood visual impairment in 1989]. AB - We studied the etiologies of visual impairment in the 171 children managed at the Alfred Peyrelongue Center, Ambares France. This center is open to visually impaired children aged 3 to 20 years and free of significant motor or cognitive handicaps. Etiologies of visual impairment in the decreasing order of frequency were as follows: cataract (31 cases), tapetoretinal degeneration (28 cases), optic nerve lesion (22 cases), retinopathy of prematurity (13 cases), coloboma malformations (13 cases), severe congenital myopia (12 cases), congenital glaucoma (10 cases), congenital nystagmus (8 cases), congenital achromatopsia (6 cases), retinal abnormalities, and ocular injuries. We discuss these results, compare them with those of a similar study carried out in the same center in 1978, and briefly review the literature. PMID- 2930125 TI - [Acute infectious cellulitis. Apropos of 28 cases]. AB - Acute infectious cellulitis is a common condition in pediatric patients. We retrospectively studied 28 cases seen over the last four years. Average age of patients was four years. Fever and a decline in general health were often found. Streptococcus pyogenes and Staphylococcus aureus were the most common organisms in our series. Outcome was favorable under early antimicrobial therapy selected according to age and clinical features. Before three months of age, cellulitis suggests a streptococcus B infection and should be treated by ampicillin or parenteral penicillin, combined with an aminoglycoside if called for. Between 4 months and 2 years of age, Haemophilus influenzae b or a pneumococcus are the most likely organisms; Haemophilus cellulitis should be treated by a third generation cephalosporin for ten days or longer, followed by ampicillin or ampicillin-clavulanic acid per os for ten or 15 days. Beyond 2-3 years of age, all organisms may be the cause of cellulitis, but the most likely are Streptococcus pyogenes and Staphylococcus aureus, treatment consists in administration of either a penicillin M or a macrolide, the route being selected according to the general condition and site of the cellulitis. PMID- 2930126 TI - ["Saber-cut" scleroderma and Parry-Romberg facial hemiatrophy. Nosologic problems. Neurologic complications]. AB - We report two cases of gradual facial hemiatrophy (Parry-Romberg syndrome). The first patient, an adolescent girl under treatment for hypothyroidism, presented with a very severe form combining advanced facial hemiatrophy, epilepsy with hemi generalized seizures and hemiatrophy of the brain. The second patient was a girl who presented with localized scleroderma resembling a saber injury, homolateral cerebral atrophy and contralateral hemiparesis. Our two cases are evidence in support of a close relationship between saber injury-like scleroderma and the Parry-Romberg syndrome. PMID- 2930127 TI - [Acute myelomonocytic leukemia with eosinophils. Apropos of a case with a cytogenetic analysis and nosologic discussion]. AB - Report of overwhelming leukemia with meningeal involvement in a 13-year-old. Cytologic and ultrastructural examinations showed features of myelomonocytic leukemia with abnormal eosinophils. The karyotype showed pericentric inversion of chromosome 16. Although these findings establish the diagnosis of acute myelomonocytic leukemia with abnormal eosinophils (M4Eo), this case ran an exceptionally severe course and exhibited some unusual cytologic features. PMID- 2930128 TI - [Fatal myocardiopathy due to adriamycin in spite of a reportedly non-dangerous cumulative dose]. AB - We report a case that illustrates the risk of major, irreversible heart failure despite theoretically safe cumulative doses of adriamycin. We discuss risk factors for cardiotoxicity, predictive methods among which echocardiography is the most useful, and preventive measures. Data are still lacking concerning long term consequences on cardiac function. Until less cardiotoxic adriamycin derivatives become available, modifications in the treatment regimen can be proposed, including a tolerance test, lower doses approximating 20 mg per week instead of 60 mg every three weeks, and administration by continuous infusion through a deep catheter or a pump as cardiotoxicity seems more dependent on drug level peaks than on total dose. These measures should reduce the hazards of adriamycin, a drug that also has potent antimitotic properties. PMID- 2930129 TI - [Treatment using Motilium of gastro-esophageal reflux associated with respiratory manifestations in children]. AB - Eighteen children aged 1 month to 12 years 8 months (mean age, 4.9 years) with pH metry proven gastroesophageal reflux (GOR)-associated chronic respiratory disorders were treated with Motilium, 2 mg/kg/d in four divided doses, for three months. The incidence of each of the respiratory manifestations decreased, and their cumulative score improved significantly at the end of the treatment period. Patient daily self-assessment scores also fell, but not significantly. Twenty-one hour pH recordings showed a significant reduction in the duration of nocturnal episodes below 4 (2.8 +/- 0.9% versus 8.2 +/- 2.6%, p less than 0.05). No side effects were recorded. Domperidone provides satisfactory control of nocturnal GOR and therefore emerges as a valuable agent for the treatment of chronic GOR associated respiratory disorders in childhood. PMID- 2930130 TI - [Primary ulcero-necrotizing enterocolitis of the newborn. Advancements in management. Improvement in prognosis]. AB - We report our experience acquired over the last seven years with the management of necrotizing enterocolitis in neonates. This condition occurs mainly in small for-dates, premature, critically ill infants. Diagnosis rests on the combination of clinical evidence of intestinal obstruction with non-specific signs of a decline in general health and suggestive roentgenographic findings. Mortality has fallen from 80% to 24% over the last eight years as a result of advances in the medical management of low-birth-weight infants, earlier treatment of bowel ischemia suspected on the basis of inconspicuous manifestations, and improvements in neonatal intensive care and surgical techniques. PMID- 2930131 TI - [Epidemiologic aspects of Campylobacter infection in hospitalized children. Evaluation of an national monitoring system]. AB - Among the data collected by the national system for the surveillance of Campylobacter infections, those concerning hospitalized children are described. During 1986 and 1987, 508 cases were reported. Among the 466 strains studied, 74% were C. jejuni strains. There were only four strains of C. fetus. All the isolates except nine were recovered from stools. Diarrhea was the most prominent symptom. Patients were more likely to be males and infants. Infections were more frequent in late summer. PMID- 2930132 TI - Influence of molybdenum and sulfur on copper metabolism in sheep: comparison of elemental sulfur and sulfate. AB - French forages usually have low levels of molybdenum, and sulfur contents are often in excess in ruminant feeds. The minimum level of molybdenum able to trigger the copper sulfur molybdenum interference in sheep was measured with either elemental sulfur or sulfate (diets enriched to 5.2 g S/kg DM). Four groups of 5 lambs weighing 35 kg received elemental sulfur and 4 increasing doses of molybdenum in the first experiment. In a second experiment, 6 groups of 5 lambs received sulfate (one group was a control group; the second received sulfate only) and 4 increasing molybdenum doses. The sulfur-molybdenum-copper interference was quantified by the plasma copper fraction insoluble in 5% trichloracetic acid (TCA insoluble copper). Whatever the form of sulfur, the interference appears with a molybdenum level of over 2.4 mg Mo/kg DM. Sulfate interferes less than elemental sulfur with the molybdenum on copper metabolism. PMID- 2930133 TI - In vitro acetylcholinesterase secretion by male or female Heligmosomoides polygyrus. AB - Acetylcholinesterase (AChE) secreted in vitro by adult male and female Heligmosomoides polygyrus were assayed over a 4-day period using a micro-method. The rate of AChE secretion by 1, 2 or 4 worms was approximately linear, and three times higher for male worms than for female worms. PMID- 2930134 TI - Corynebacterium pseudotuberculosis: biochemical properties, production of toxin and virulence of ovine and caprine strains. AB - Twenty-two strains of Corynebacterium pseudotuberculosis, the causative agent of caseous lymphadenitis, were isolated from typical abscesses in sheep and goats from flocks in 6 different regions of France and were characterized. These strains were uniform in biochemical characteristics, susceptibility to 8 antimicrobial agents, and virulence for OF1 mice. All these strains produced an exotoxin, identified by inhibition of staphylococcal beta-hemolysin. Moreover, this study showed that strain 19R, a streptomycin-resistant mutant used in experimental infection in sheep, possessed the same characteristics as the field strains of C. pseudotuberculosis, except for its resistance to streptomycin (500 micrograms/ml). PMID- 2930135 TI - [Persistence of serologic and allergic reactions in ewes after vaccination with the H.38 or Rev.1 vaccines in a brucellosis (Brucella melitensis) enzootic area]. AB - In a flock of 2,000 ewes located in an endemic area of Brucella melitensis infection, subjected to systematic vaccination of lambs either with killed and adjuvanted B. melitensis H.38 vaccine from 1973 to 1978, or with living B. melitensis Rev.1 vaccine since 1979, reactions to allergic intrapalpebral test, complement fixation test and Rose Bengal plate test were recorded in small groups of animals vaccinated four, three, two or one years ago. Four years after H.38 vaccination, 39 ewes out of 40 (97%) remained positive at least to one of the three tests. After vaccination with strain Rev.1, 16% out of 153 ewes vaccinated one to four years before were positive. These results were discussed according to two aspects: 1) infectious or vaccinal origins of these positive reactions; 2) consequences on implement of test and slaughter procedures in a vaccinated flock: allergic or complement fixation tests would have led to eliminate 9% out of ewes vaccinated with the Rev.1 vaccine, but only 1% with the Rose Bengal plate test. PMID- 2930136 TI - [Development and survival of free-living stages of Trichostrongylidae of sheep on irrigated pastures in Zaragoza (Spain)]. AB - Twelve small plots (2 x 2 m) progressively received parasitised faeces on two occasions between July 1980 and February 1983. They were sprinkled from March to October. Egg and larval populations dynamics in faeces and herbage were followed. Teladorsagia and Trichostrongylus could develop all through the year, at lower speed and rate during cold months. Haemonchus larvae were observed only from May to October. With irrigation, eggs developed into infective larvae in 2-4 weeks, peaks of larvae on grass occurred in weeks 4 to 5. The maximum number of L3/100 eggs was 11.3 for Teladorsagia, 6.99 for Trichostrongylus and 10.65 for Haemonchus, after July faeces deposit. PMID- 2930137 TI - [Bovine brucellosis caused by Brucella melitensis in France]. AB - Each Brucella species is known to have a definite host preference. In this respect, brucellosis in cattle is primarily due to B. abortus. As part of an investigation of the species and biovars responsible for bovine brucellosis in France, 312 strains have been examined since 1978 by the methods recommended by the Subcommittee on the Taxonomy of the genus Brucella. Of these, 264 (85%) were indeed classified as B. abortus members. However the 48 others (15%) had all the characteristics that define the species B. melitensis which usually affects small ruminants. Of these 48 strains, 43 (90%) came from the southern part of France in which B. melitensis infection in sheep and goats is enzootic and where the dissemination of this species by sheep flocks moving to mountain pastures most often accounted for cattle contamination. Evidence that B. melitensis infection in cattle traced to infected small ruminants was also strongly supported by biotyping. Of the 48 strains, 45 (94%) indeed were B. melitensis biovar 3 which is the most common in infected sheep and goats in France. B. melitensis infected cattle, which also constitutes a serious risk for public health, must therefore be considered by veterinary authorities because of epizootiologic implications in eradication and control programmes of sheep and goat brucellosis. PMID- 2930138 TI - [Esophagectomy without thoracotomy using a stripping method: technic, results, indications in benign and malignant diseases of the esophagus]. AB - A technique of esophagectomy without thoracotomy using a stripper with limited dissection of the mediastinum has been applied to 48 patients: neoplasia in 41 (squamous-cell carcinoma of the esophagus: 34, carcinoma of the gastric cardia: 5, pharyngeal carcinoma: 2) and non-malignant pathology in 7 (2 caustic necroses, 2 ruptured esophagus, 2 anastomotic leakages after gastro-esophageal resection, 1 caustic stenosis). There were 3 post-operative deaths. The best indications of this procedure are extended tumors of the lower esophagus in poor-risk patients, and perhaps superficial carcinomas of the esophagus whatever the site. The usefulness of this technique in such situations as perforations and mediastinitis is emphasized. PMID- 2930139 TI - [Harris and Galante non-cemented total hip prosthesis. 1st results]. AB - Amongst the various models of total hip prosthesis available on the market, the Harris and Galante non-cemented implant constitutes an attractive alternative. The authors report their preliminary experience on the basis of a limited series (77 hips) and a follow-up of 6 to 30 months. The hemispherical acetabular prosthesis, which is very easy to use, induces a local reaction in about 10% of cases. The femoral pivot, inserted by means of a very sophisticated apparatus, is more frequently responsible for local reactions (4 circumferential rings, 2 of which were asymptomatic, and 24 partial rings particularly in Gruen's zone 1). Although the preliminary results of this short series appear to be encouraging (59 operated patients out of 63 were scored as D5 - D6), a longer follow-up is nevertheless essential. PMID- 2930140 TI - [Subtotal avulsion of the lower limb after traumatic section in a 2 and a half year-old child]. AB - Reimplantation after subtotal section of the right lower limb under the Scarpa triangle was been attempted and was successful. Section and contusion of the femoral artery and vein required 2 end-to-end saphenous bypass grafts. The use of the lower limb is correct, after to a follow up of 4 years. The risks, inherent to all proximal section, with important muscular masses, in a small child, are described. Functional prognosis depends on three aspects: bone, vessels, and nerves. A tibial pseudarthrosis had to be operated secondarily with significant lengthening. A partial stenosis of the graft was demonstrated arteriographically. Pes equinus, a result of paralysis, has been fitted with an orthesis. This observation is almost an experimental one: what can be the future of a reimplanted lower limb in the child. PMID- 2930141 TI - [Ileo-anal anastomosis: various types of ileal reservoir]. AB - The creation of an ileal reservoir ensures an improvement in the functional result obtained after ileo-anal anastomosis. As a result of its storage function, the reservoir allows a reduction in the number of stools per day. Several types of reservoir have been described. The S-shaped reservoir consists of three aniso peristaltic limbs and an efferent loop with end-to-end ileo-anal anastomosis. The W reservoir is equivalent to a double J reservoir. The side-to-side iso peristaltic reservoir consists of two iso-peristaltic limbs and an efferent loop with end-to-end ileo-anal anastomosis. After analysing the specific characteristics of each type of reservoir, the authors conclude that the necessity of a reservoir no longer needs to be demonstrated, but that there is no formal argument in favour of one particular model. PMID- 2930142 TI - [Usefulness of a colonic reservoir after resection of the rectum]. AB - Resection of the rectum followed by low colo-rectal anastomosis or colo-anal anastomosis may result in functional modifications. A brief retrospective study of 210 cases showed that the considerable alterations (urgency, frequent stools) are essentially due to very low colo-rectal, supra-anal anastomoses. It would therefore be interesting to evaluate the result of colo-anal anastomoses with colonic reservoir in this group of patients. PMID- 2930144 TI - [Inflammatory and neoplastic esophagotracheal fistula. Intubation or surgery?]. AB - There are two principal aetiologies for oesophago-tracheal fistulae: cancer of the oesophagus opening into the airways and assisted ventilation (tracheotomy or nasotracheal intubation). Oesophago-tracheal fistulae are rare. Over a period of 6 years, the authors have treated 9 neoplastic oesophago-tracheal fistulae in a series of 150 cases of oesophageal cancer and 2 inflammatory oesophago-tracheal fistulae out of a series of more than 20 stenoses of the same nature. The two types of oesophago-tracheal fistulae have the same degree of severity but very different significance, treatment and prognosis: neoplastic oesophago-tracheal fistulae, an advanced, often terminal form of oesophageal cancer, justify palliative treatment to exclude the respiratory tract. Endoscopic intubation of the oesophagus is generally appropriate treatment. Exceptionally, a surgical bypass of the oesophagus may be proposed. Inflammatory oesophago-tracheal fistulae require treatment to restore the continuity of the trachea and oesophagus in patients with respiratory autonomy. In agreement with H. Grillo, we consider treacheal resection-suture and repair of the oesophageal defect to constitute the most satisfactory procedure. PMID- 2930143 TI - [Ultrasound-guided puncture. A modern treatment of liver abscess]. AB - The treatment of liver abscesses has benefitted from progress in imaging, particularly ultrasonography which allows simple and reliable aspiration and drainage. A series of 32 cases is reported, consisting of 29 pyogenic abscesses and 3 amoebic abscesses. Eighty-one per cent of patients were cured by aspiration and/or drainage, while 19% of patients had to be operated. The mean hospital stay was 11 days. Failures of ultrasound-guided aspiration are essentially due to multifocal abscesses caused by multiple organisms. PMID- 2930145 TI - [Contribution of x-ray computed tomography in acute pancreatitis]. AB - Computed tomography in acute pancreatitis provides a radiological definition by distinguishing between lesions of the peri-pancreatic space and distant tracks. The angioscanner is essential for the definition of glandular lesions and to evaluate the existence and extent of the necrosis. The prognostic evaluation during the initial phase of the disease is not more reliable with computed tomography than with classical clinical ad laboratory signs. However, the combination of the two seems to more accurately predict the prognosis. The morphological follow-up of the course of the lesions is essential in order to recognise the abscess. Computed tomography is the best method for following the course of necrotic fluid collections and of identifying secondary infection by means of guided aspiration. Surgical evacuations of the abscesses may be performed through incisions adapted to their site, as defined by computed tomography. PMID- 2930146 TI - [Acute severe pancreatitis: limitations of medical treatment]. AB - The natural course of severe acute pancreatitis can be divided into two successive phases. The initial phase is characterized by the systemic manifestations resulting from the acute inflammatory response that takes place in the pancreas. The second stage reflects the progression of pancreatic necrosis towards spontaneous resolution, pseudocyst formation or secondary infection. While the treatment of these latter complications mainly consists of surgery (drainage of pseudocyst/infected necrosis) prevention and management of the initial systemic complications of acute pancreatitis is essentially involves medical therapy (empirical treatment, percutaneous peritoneal dialysis and thoracic duct drainage). Only the simultaneous and appropriate use of these various therapeutic modalities can ensure a substantial reduction in the mortality of severe acute pancreatitis. The place of these therapeutic approaches is discussed. PMID- 2930147 TI - [Hemorrhagic gastroduodenal ulcer: when is it necessary to operate?]. AB - In the context of severe haemorrhage from peptic ulcers, surgery remains the safest method of haemostasis, but at the cost of a relatively high mortality. The time of surgery constitutes one of the prognostic factors. It has been demonstrated that the mortality increases significantly with the delay in operation and recurrent haemorrhages; it is therefore important to operate rapidly on patients at risk of recurrence and therefore to determine the clinical and endoscopic criteria capable of predicting this recurrence. PMID- 2930148 TI - [Excision of colorectal cancers: what can be expected of lymph node excision?]. AB - We report a series of 413 patients with colo-rectal adenocarcinoma. 328 had a curative resection and 277 of them had elective lymphadenectomy; 51 had no lymphadenectomy because of either age or poor general status. Operative morbidity and mortality were not increased by lymphadenectomy. Survival was related to the lymph node involvement: 70.6% 5 year survival in patients without lymph node metastases, 49.3% 5 year survival in patients with lymph node metastases (P less than 0.001). However lymphadenectomy did not affect the survival rate of the patients. We conclude that lymphadenectomy had no deleterious effect. However, its real benefit on long term survival must be evaluated in further prospective randomised studies. PMID- 2930149 TI - [Comparative study of pulsed and continuous Doppler in the quantification of aortic insufficiency]. AB - 31 patients whose mean age was 61 +/- 29 yrs. presenting with aortic regurgitation (AR) benefited from cardiac catheterization which was preceded by Doppler ultrasound examination in a prospective study to compare the diagnostic contributions made by continuous vs pulsed wave techniques respectively in the quantitative assessment of AR, with reference to semi-quantitative angiographic evaluation. Pulsed Doppler analysis involves mapping of the left ventricle in two projections as well as the investigation of blood flow in the aortic isthmus using a suprasternal approach. Collection of continuous wave signals from the cardiac apex makes it possible to measure circulatory deceleration and the half time of decrease in signal velocity and the protodiastolic pressure gradient. Our results corroborate the reliability of data obtained using continuous-wave Doppler technique in finding significant correlations for each parameter respectively: r' = 0.88 (p less than 0.001); r' = -0.81 (p less than 0.001); r' = -0.75 (p less than 0.001). Values determined by pulsed wave Doppler mapping of the left ventricle appear to be less satisfactory but are significant: r' = 0.68 (p less than 0.001) while measurement of end-diastolic blood flow recorded in the isthmus of the aorta is more highly correlated: r' = 0.84 (p less than 0.01), with the main disadvantage being its limited applicability to a small number of our patients (48%). We thus concluded that continuous-wave Doppler ultrasound is a better technique in the quantitative evaluation of AR, while recalling the essential additional value of pulsed-wave Doppler technique to localize the leakage and of ultrasound to assess its impact on the left ventricle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2930150 TI - [Anti-arrhythmia efficacy of propafenone per os in the prevention of paroxysmal supraventricular arrhythmia resistant to class Ia agents]. AB - The efficacy of orally administered propafenone in the prevention of paroxysmal supraventricular dysrhythmias (atrial fibrillation, atrial tachysystole, reciprocal tachycardia) resistant to Vaughan-Williams class Ia drugs was investigated in 10 patients. Propafenone controlled dysrhythmia very well in 4 out of the ten patients, and satisfactorily in another one at a dosage ranging from 450 to 900 mg/day in 3 or 4 divided doses; this result was documented using continuous 24 hr. Holter ECG monitoring. Among the 5 clinical failures, 1 patient had atrial fibrillation primarily at night, and another poorly tolerated this agent which led to interrupt therapy. PMID- 2930151 TI - Too much togetherness can be stifling. PMID- 2930152 TI - Nursing 'too feminine' for men? PMID- 2930153 TI - Endometriosis etiology questioned. PMID- 2930155 TI - Health officials discuss screening for HTLV-I. PMID- 2930154 TI - Legal aspects of whistle-blowing. PMID- 2930156 TI - The orientation process. Strategies to ensure success. AB - The companion article by Erika Britton, RN, offers the learner's view of the orientation process. As perioperative nursing becomes more complicated, the orientation process should become more sophisticated to address the issues of recruitment, retention, and mastery of skills. Traditional teaching methods may not always meet the needs of perioperative nurses. As one author stated: If nurses really want to see nursing achieve professional status, each of us- educators, administrators, and practitioners--must reexamine our interactions with novice nurses. We have to stop eating our young. These newly prepared nurses are the profession's future. If they are not nurtured as they develop, professional extinction beckons. Our young are not only the new graduate nurses but any nurse from novice to expert who needs to be oriented. We must recognize their needs and plan effectively for their orientation. PMID- 2930157 TI - The orientation process. A learner's view. PMID- 2930158 TI - Nursing in England. A view from across the Atlantic. PMID- 2930160 TI - Enjoying management. The positive benefits of liking the job. AB - Enjoying one's work is a state of mind that is integrated in the manager's personality. Although some individuals are born with an optimistic perspective on life, others have to develop it. A manager can cultivate an appreciation for the ordinary and learn to use humor as a communication tool and coping technique. Cultivating this orientation cannot be limited to the work setting but must be developed in relation to life. Health care agencies are complex and turbulent organizations. Whether the nurse manager is climbing the career ladder or just trying to be successful on the job, enjoying work can be a key ingredient to success. Nurse managers must both manage and lead. An attitude of enjoyment and pleasure at work is a trait that allows the manager to extend administration from managing to leading. PMID- 2930159 TI - Pay for performance. Implementing a financial incentive for excellent work. AB - Based upon my own experience with the system, both staff and supervisors believe that the advantage of pay for performance outweigh the disadvantages. I frequently encountered issues such as how to get a higher rating, what is the incentive to identify a difficult objective if one can pick an easier objective and still receive a higher rating, and where do individuals fall in the ratings compared to peers. In response to achieving a higher rating, the supervisors reviewed the rating system and developed objectives that would receive higher ratings. The supervisors and administrators put emphasis on improved performance, rather than on points. To convince employees to choose more difficult objectives, we explained that objectives should reflect the skills and goals of each employee. The objective serves as an indicator of how well the employee achieved a goal. In dealing with the ranking problem, we told the staff where they ranked in relation to others (eg, top, middle, bottom), but emphasized that the evaluation is confidential and that the results are not to be shared. In conclusion, pay for performance offers a supervisor a detailed objective format for reviewing an employee's performance. For the employees, it provides a means in which their performance review is based on individual achievement of self selected objectives. Employees are measured against their own standards rather than being compared with others performing the same job. PMID- 2930161 TI - Substandard disinfection deactivates AIDS virus. PMID- 2930162 TI - Professional maturity. The stages of developing self-esteem. PMID- 2930163 TI - Proposed recommended practices. Monitoring the patient receiving local anesthesia. AORN Recommended Practices Subcommittee of the TPCC. PMID- 2930164 TI - Proposed recommended practices. Radiological safety in the operating room. AORN Recommended Practices Subcommittee of the TPCC. PMID- 2930165 TI - All nurses, regardless of education, should unite. PMID- 2930166 TI - Operating room practices: myth or science? PMID- 2930168 TI - Removal of methanethiol, dimethyl sulfide, dimethyl disulfide, and hydrogen sulfide from contaminated air by Thiobacillus thioparus TK-m. AB - Methanethiol, dimethyl sulfide, dimethyl disulfide, and hydrogen sulfide were efficiently removed from contaminated air by Thiobacillus thioparus TK-m and oxidized to sulfate stoichiometrically. More than 99.99% of dimethyl sulfide was removed when the load was less than 4.0 g of dimethyl sulfide per g (dry cell weight) per day. PMID- 2930167 TI - The suicide phenomenon in motile aeromonads. AB - Certain strains of motile Aeromonas species, including all those of Aeromonas caviae examined, were shown to be suicidal. When they were grown in the presence of glucose at both 30 and 37 degrees C, there was rapid die-off of the organisms after 12 h of incubation, and viable cells generally could not be recovered after 24 h. It was shown that this phenomenon was due to the production of relatively high levels of acetic acid by these strains, even during growth under highly aerobic conditions, and to the greater susceptibility of these strains to acetic acid-mediated death. Suicide did not occur when the pH was maintained above 6.5 or in the presence of high concentration of Pi. These observations were consistent with our inability to isolate suicidal Aeromonas spp. from acidic lakes in New England and with their recovery from alkaline waters in Israel and from sewage. Suicidal aeromonads appear to be better adapted than the nonsuicidal biotypes to anaerobic growth in low-nutrient environments. PMID- 2930169 TI - Effects of zinc, iron, cobalt, and manganese on Fusarium moniliforme NRRL 13616 growth and fusarin C biosynthesis in submerged cultures. AB - The influence of zinc, iron, cobalt, and manganese on submerged cultures of Fusarium moniliforme NRRL 13616 was assessed by measuring dry weight accumulation, fusarin C biosynthesis, and ammonia assimilation. Shake flask cultures were grown in a nitrogen-limited defined medium supplemented with various combinations of metal ions according to partial-factorial experimental designs. Zinc (26 to 3,200 ppb [26 to 3,200 ng/ml]) inhibited fusarin C biosynthesis, increased dry weight accumulation, and increased ammonia assimilation. Carbohydrate was found to be the principal component of the increased dry weight in zinc-supplemented cultures. Zinc-deficient cultures synthesized more lipid and lipidlike compounds, such as fusarin C, than did zinc supplemented cultures. Microscopic examination showed that zinc-deficient hyphae contained numerous lipid globules which were not present in zinc-supplemented cultures. Addition of zinc (3,200 ppb) to 2- and 4-day-old cultures inhibited further fusarin C biosynthesis but did not stimulate additional dry weight accumulation. Iron (10.0 ppm) and cobalt (9.0 ppm) did not affect fusarin C biosynthesis or dry weight accumulation. Manganese (5.1 ppm) did not affect dry weight accumulation but did increase fusarin C biosynthesis in the absence of zinc. Maximum fusarin C levels, 32.3 micrograms/mg (dry weight), were produced when cultures were supplied manganese, whereas minimum fusarin C levels, 0.07 micrograms/mg (dry weight), were produced when zinc, iron, cobalt, and manganese were supplied. These results suggest a multifunctional role for zinc in affecting F. moniliforme metabolism. PMID- 2930170 TI - Use of a biotinylated DNA probe to detect bacteria transduced by bacteriophage P1 in soil. AB - Presumptive bacteriophage P1 transductants of Escherichia coli, isolated from soil inoculated with lysates of transducing phage P1 and E. coli, were confirmed to be lysogenic for phage P1 by hybridization with a biotinylated DNA probe prepared from the 1.2-kilobase-pair HindIII 3 fragment of bacteriophage P1. No P1 lysogens of indigenous soil bacteria were detected with the DNA probe. The sensitivity and specificity of the DNA probe were assessed with purified and dot blot DNA, respectively. In addition, two techniques for the lysis and deproteinization of bacteria and bacteriophages on nitrocellulose filters were compared. These studies indicated that biotinylated DNA probes may be an effective alternative to conventional radiolabeled DNA probes for detecting specific gene sequences in bacteria indigenous to or introduced into soil. PMID- 2930171 TI - Studies on mixed populations of human intestinal bacteria grown in single-stage and multistage continuous culture systems. AB - Mixed intestinal bacteria were grown for 336 h in two identical single-stage chemostats at low growth rates in a carbohydrate-limited medium. Complex bacterial populations were maintained and anaerobes always outnumbered aerobes. The predominant organisms belonged to the genera Bacteroides, Bifidobacterium, Lactobacillus, Clostridium, Eubacterium, Propionbacterium, Peptococcus, and Peptostreptococcus. Bacteroides species predominated in both fermentors, particularly B. ovatus and B. thetaiotaomicron. A high degree of reproducibility of bacteriological and fermentation product data was obtained in these experiments. When gut contents were inoculated into a five-stage continuous culture system (retention time of 79 or 38 h) containing soya bran, the medium flow rate had little quantitative effect on the formation of acidic fermentation products; however, more oxidized fermentation acids were produced at the higher retention time. Diverse bacterial populations were maintained in every vessel at each flow rate. Bacteroides fragilis group organisms, especially B. ovatus, were numerically the most important. The viability of bacteria decreased through the system, especially at a retention time of 79 h, when the bacteria were growing under severely nutrient-limited conditions. PMID- 2930172 TI - Effect of thermal additions on the density and distribution of thermophilic amoebae and pathogenic Naegleria fowleri in a newly created cooling lake. AB - Pathogenic Naegleria fowleri is the causative agent of fatal human amoebic meningoencephalitis. The protozoan is ubiquitous in nature, and its presence is enhanced by thermal additions. In this investigation, water and sediments from a newly created cooling lake were quantitatively analyzed for the presence of thermophilic amoebae, thermophilic Naegleria spp., and the pathogen Naegleria fowleri. During periods of thermal additions, the concentrations of thermophilic amoebae and thermophilic Naegleria spp. increased as much as 5 orders of magnitude, and the concentration of the pathogen N. fowleri increased as much as 2 orders of magnitude. Concentrations of amoebae returned to prior thermal perturbation levels within 30 to 60 days after cessation of thermal additions. Increases in the thermophilic amoeba concentrations were noted in Savannah River oxbows downriver from the Savannah River plant discharge streams as compared with oxbows upriver from the discharges. Concentrations of thermophilic amoebae and thermophilic Naegleria spp. correlated significantly with temperature and conductivity. Air samples taken proximal to the lake during periods of thermal addition showed no evidence of thermophilic Naegleria spp. Isoenzyme patterns of the N. fowleri isolated from the cooling lake were identical to patterns of N. fowleri isolated from other sites in the United States and Belgium. PMID- 2930173 TI - Selective medium for isolation of Xanthomonas maltophilia from soil and rhizosphere environments. AB - A selective medium (XMSM) was developed for isolation of Xanthomonas maltophilia from bulk soil and plant rhizosphere environments. The XMSM basal medium contained maltose, tryptone, bromthymol blue, and agar. Antibiotics added to select for X. maltophilia were cycloheximide, nystatin, cephalexin, bacitracin, penicillin G, novobiocin, neomycin sulfate, and tobramycin. A comparison was made between XMSM and 1/10-strength tryptic soy broth agar for recovery of X. maltophilia from sterile and nonsterile soil infested with known X. maltophilia isolates. A recovery rate of 97% or greater for XMSM was demonstrated. XMSM was used to isolate X. maltophilia from a variety of soil and rhizosphere environments. PMID- 2930174 TI - Isolation and identification of Pseudomonas spp. from Schirmacher Oasis, Antarctica. AB - Ten cultures of Pseudomonas spp. were established from soil samples collected in and around a lake in Antarctica. Based on their morphology, biochemical and physiological characteristics, and moles percent G + C of their DNA, they were identified as P. fluorescens, P. putida, and P. syringae. This is the first report on the identification of Pseudomonas spp. from continental Antarctica. PMID- 2930175 TI - The lone researcher. PMID- 2930177 TI - Researching research: a method for promoting positive attitudes. AB - It is widely agreed that nursing research needs to be more effectively taught and that new strategies are needed to involve nurses more intently in the research process, both as students and professionals. Two areas that appear to be in particular need of attention are the utilization of research findings in nursing practice and the development of positive attitudes toward research. This article describes a strategy designed to help nursing students over two hurdles--their initial unfamiliarity with the process of finding, evaluating, and applying research and their inhibitions toward the process--by getting them involved in doing research on research and actually presenting and publishing their own findings. PMID- 2930176 TI - Surgery for morbid obesity: the patients' experiences. AB - A survey of 123 adult patients who had undergone surgery for the treatment of morbid obesity was conducted to obtain data on patients' perceptions of preparation for surgery, care received during hospitalization, postoperative physical changes, changes in food tolerance, self-concept before and after surgery, work experience before and after surgery, and the relative importance of various forms of follow-up care. The study has implications for nursing practice in early diagnosis of patient problems, improved anticipatory teaching, and better training of health care professionals to assist the morbidly obese patient. The tolerable and nontolerable food lists generated from the data represent a significant contribution to patient care. PMID- 2930178 TI - Hope-inspiring strategies of the critically ill. AB - Sixty persons who had been critically ill were studied to determine what mechanisms they used to maintain or increase their hope while confronting a life threatening event. Patients were interviewed 2 to 4 days after discharge from a critical care unit. Responses to the interviews were categorized into nine hope inspiring themes. The findings provide direction for developing strategies to inspire hope in the critically ill. PMID- 2930179 TI - Child abuser stereotypes: consensus among clinicians. AB - This article reports the results of an investigation of nurses' stereotypes of child abusers. Ninety-four registered nurses completed a questionnaire that measured subjects' knowledge of child abuse; professional contact with perpetrators and victims of abuse; knowledge of the causes of child abuse; and child abuser stereotypes. Results reveal a consensus among the subjects as to the stereotypes associated with child abusers. This study supports the notion that nurses stereotype individuals on the basis of demographic characteristics. This study also raises questions regarding the bias that may result from the use of child abuser stereotypes. Clinical decision-making processes could become compromised if biased judgements are used in planning nursing care for clients diagnosed as child abusers. PMID- 2930180 TI - Family caregivers: the experience of Alzheimer's disease. AB - This qualitative, interpretive study generated a model to describe the course of Alzheimer's disease (AD) as experienced by family caregivers in interaction with an afflicted relative. Stages of experiencing AD from a family caregiver's perspective were identified. These included Stage 1: noticing; Stage 2: discounting and normalizing; Stage 3: suspecting; Stage 4: searching for explanations; Stage 5: recasting; Stage 6: taking it on; Stage 7: going through it; and Stage 8: turning it over. Since describing typical stages of Alzheimer's dementia by focusing on the patient's symptoms has generated controversial results, this study shifted the focus to the lived experience of family caregivers. It supports prior contentions that patterns and progression in patients themselves are variable; however, families can be offered knowledge about the disorder's course to ease their fears and their difficulties in interpreting interactions with their demented relatives. The study is based on "methods for discovering" theory. A purposeful sample of 20 caregivers was interviewed for at least 2 hours in their own homes. All caregivers held primary responsibility for home care for a demented relative and had consented to participate in the study. PMID- 2930181 TI - Cigarette craving during the immediate postcessation period. PMID- 2930182 TI - Home care support program for frail elderly clients. PMID- 2930183 TI - Spouses' experiences during pregnancy and the postpartum. PMID- 2930184 TI - The home visit for data collection. PMID- 2930185 TI - Hydrogen-1 nuclear magnetic resonance studies of staphylococcal nuclease variant H124L: pH dependence of histidines and tyrosines. AB - The pH dependence of the 1H NMR spectrum of staphylococcal nuclease H124L was investigated as a function of the binding of Ca2+, the ion required for enzymatic activity, and deoxythymidine-3',5'-diphosphate (pdTp), a competitive inhibitor. The protein studied was the product of a cloned gene expressed in Escherichia coli which yields a protein having a sequence identical to that of the nuclease isolated from the V8 strain of Staphylococcus aureus. Of the observable ring protons of the three histidine residues, only the C delta 1H of His46 shows a large chemical shift perturbation on formation of the ternary complex, (nuclease H124L).pdTp.Ca2+. The pKa of His46 is lowered by 0.2 pH unit in the binary complex. All seven tyrosines titrate with normal pKa values between 9 and 11 in the unligated nuclease. In the ternary complex, however, the pKa values of Tyr85 and Tyr93 increase above pH 11.0. The chemical shift perturbations of the ring protons of the Tyr27, Tyr85, Tyr113, and Tyr115 were observed between pH 4 and 6; these spectral perturbations are attributed to interactions with carboxylate groups. Binding Ca2+ alone acted opposite to the perturbation in Tyr113 and Tyr115. Ca2+ binding leads to deshielding the ring protons of Tyr113, but this effect is removed in the ternary complex. Binding of pdTp and Ca2+ stabilizes the protein against high pH denaturation up to pH 11.5. PMID- 2930186 TI - Purification and properties of ornithine carbamoyl transferase from liver of Squalus acanthias. AB - Citrulline synthesis from ammonia by hepatic mitochondria in elasmobranchs involves intermediate formation of glutamine as the result of the presence of high levels of glutamine synthetase and a unique glutamine- and N-acetyl glutamate-dependent carbamoyl phosphate synthetase, both of which have properties unique to the function of glutamine-dependent synthesis of urea, which is retained in the tissues of elasmobranchs at high concentrations for the purpose of osmoregulation [P.M. Anderson and C.A. Casey (1984) J. Biol. Chem. 259, 456 462; R.A. Shankar and P.M. Anderson (1985) Arch. Biochem. Biophys. 239, 248-259]. The objective of this study was to determine if ornithine carbamoyl transferase, which catalyzes the last step of mitochondrial citrulline synthesis and which has not been previously isolated from any species of fish, also has properties uniquely related to this function. Ornithine carbamoyl transferase was highly purified from isolated liver mitochondria of Squalus acanthias, a representative elasmobranch. The purified enzyme is a trimer with a subunit molecular weight of 38,000 and a native molecular weight of about 114,000. The effect of pH is significantly influenced by ornithine concentration; optimal activity is at pH 7.8 when ornithine is saturating. The apparent Km values for ornithine and carbamoyl phosphate at pH 7.8 are 0.71 and 0.05 mM, respectively. Ornithine displays considerable substrate inhibition above pH 7.8. The activity is not significantly affected by physiological concentrations of the osmolyte urea or trimethylamine-N-oxide or by a number of other metabolites. The results of kinetic studies are consistent with a steady-state ordered addition of substrates (carbamoyl phosphate binding first) and rapid equilibrium random release of products. Except for an unusually low specific activity, the properties of the purified elasmobranch enzyme are similar to the properties of ornithine carbamoyl transferase from mammalian ureotelic and other species and do not appear to be unique to its role in glutamine-dependent synthesis of urea for the purpose of osmoregulation. PMID- 2930187 TI - Characterization of the maturation-associated galactose oxidase-sensitive glycoproteins of rat caudal sperm plasma membrane and epididymal fluid. AB - This paper explores the relationship between the galactose oxidase-sensitive glycoproteins from rat caudal epididymal sperm and fluid and, in addition, their relatedness to the 32,000-Da major acidic secretory glycoproteins of caudal epididymal fluid. The major acidic secretory glycoproteins were purified by a combination of high-resolution anion-exchange (Mono Q) and gel permeation (Bio Sil TSK 125) chromatographic steps. Immunoprecipitation studies, peptide mapping, and the inability to label the purified glycoprotein by galactose oxidase/sodium boro[3H]hydride clearly established that the galactose oxidase-sensitive fluid and membrane glycoproteins were not related to these acidic secretory glycoproteins. Membrane and fluid tritium-labeled glycoproteins were shown to be closely related, but not identical, polypeptides. Sugar analysis indicated that both glycoproteins contain N- and O-linked saccharide chains and that the galactose oxidase-sensitive residue was present only on O-linked sugars. It was also found that efficient labeling of the 32,000-Da fluid glycoprotein was possible only if protease inhibitors were omitted from all buffers used in the isolation of caudal epididymal fluid and subsequent labeling procedures. This suggests that the fluid glycoprotein was acquired by the unintentional proteolysis of the membrane glycoprotein. Polyclonal antibodies raised against caput sperm plasma membranes immunoprecipitated tritium-labeled glycoproteins from both caudal epididymal fluid and sperm membrane, suggesting that a precursor form of the caudal galactose oxidase-sensitive glycoprotein may be present on caput sperm. PMID- 2930188 TI - Tryptophan 2,3-dioxygenase activity in rat skin. AB - We have found an enzyme system that catalyzes the conversion of L-tryptophan to L kynurenine, presumably via L-formylkynurenine, in soluble and insoluble fractions of rat skin. The enzymatic activity was stimulated by hematin, ascorbate, and catalase, but not by methylene blue. Highest activity was located in the skin of the dorsal posterior region and lowest activity in the abdominal region. The activity in plucked (depilated) skin was only about 25% of that obtained from unplucked (depilated) tissue of the same region. D-Tryptophan, 5 hydroxytryptophan, and tryptamine were not degraded by the skin enzyme and the Km for L-tryptophan determined with the crude enzyme was 1 microM. The decycling activity of rat skin and liver for L-tryptophan began to be stimulated after birth and reached the highest level at 6 weeks. But, 1 week later, most of the skin activity suddenly disappeared and the low level continued at least until 12 weeks. In contrast, the hepatic enzyme did not change so drastically. These findings suggest that an enzyme that catalyzes L-tryptophan to L-kynurenine via L formylkynurenine is present in rat skin. PMID- 2930189 TI - Studies on asparagine-linked protein glycosylation in differentiating skeletal muscle cells. AB - The embryonic development of skeletal muscle proceeds by the adherence and fusion of myoblast cells to form multinucleated myotubes. In the present study, enzymes in the dolichol pathway for asparagine-linked glycoprotein synthesis and oligosaccharide chain composition were characterized in myoblasts and myotubes derived from the C2 (mouse) muscle cell line. The N-acetylglucosaminyltransferase responsible for chain initiation and the mannosyl- and glucosyltransferases for Dol-P-Man and Dol-P-Glc synthesis were characterized with respect to substrate, cation, and detergent dependence. Time course studies in the absence and presence of exogenous Dol-P revealed that myoblasts had a two- to threefold higher capacity than myotubes for Dol-sugar synthesis. Pulse-chase experiments following the elongation of the Dol-oligosaccharide by intact cells showed myoblasts to label oligosaccharide intermediates approximately fourfold greater than myotubes; myotubes, however, were more efficient than myoblasts for converting the intermediates to the glucosylated Dol-tetradecasaccharide. Oligosaccharide chains isolated from sarcolemma glycopeptides were analyzed by Con A, WGA, and QAE chromatography. There were no differences between myoblast and myotube oligosaccharides with respect to the proportion of tri-tetraantennary complex, biantennary complex, and high mannose chains. Hybrid chains were not detected. The major high mannose chain contained nine mannose residues. Sialyltransferase activity was identical. The results suggest that higher levels of Dol-P and protein acceptor contribute to the greater degree of protein glycosylation in myoblast vs myotube muscle cells. PMID- 2930190 TI - Identification of histidyl peptide labeled by 2-(4-bromo-2,3 dioxobutylthio)adenosine 5'-monophosphate in an ADP regulatory site of glutamate dehydrogenase. AB - Bovine liver glutamate dehydrogenase reacts covalently with 2-(4-bromo-2,3 dioxobutylthio)adenosine 5'-monophosphate (2-BDB-TAMP) with incorporation of 1 mol reagent/mol enzyme subunit and loss of one of the two ADP sites of native enzyme [S. P. Batra and R. F. Colman, J. Biol. Chem. 261, 15565-15571 (1986)]. Incorporation of reagent is prevented specifically by ADP. The modified enzyme has now been digested with trypsin. The nucleotidyl peptide has been purified by chromatography on phenylboronate-agarose, followed by reverse-phase HPLC. On the basis of amino acid composition following acid hydrolysis, and gas-phase sequencing, the modified tryptic peptide was established as Ala-Gln-His-Ser-Gln His-Arg, corresponding to amino acids 80-86 of the known glutamate dehydrogenase primary structure. The evidence presented indicates that the target amino acid attacked by 2-BDB-TAMP is histidine-82 and that this residue is located within the high-affinity ADP-activating site of glutamate dehydrogenase. In the course of this work, it was found that the positions of Gln84 and His85 had been reported as reversed in the revised sequence of bovine liver glutamate dehydrogenase [J. H. Julliard and E. L. Smith, J. Biol. Chem. 254, 3427-3438 (1979)]. Three additional corrections are here reported in the amino acid sequence of the native enzyme on the basis of gas-phase sequencing of other peptides purified by HPLC: Asp168 (not Asn); His221-Gly222 (not Gly-His); and Glu355 (not Gln). PMID- 2930191 TI - The properties of peptidyl diazoethanes and chloroethanes as protease inactivators. AB - Earlier work has demonstrated the irreversible inactivation of serine and cysteine proteinases by peptides with a C-terminal chloromethyl ketone group. With a C-terminal diazomethyl ketone, on the other hand, peptides become reagents specific for cysteine proteinases. We have now synthesized and examined the properties of reagents with an additional methyl side chain near the reactive grouping with the goal of diminishing side reactions in a cellular environment. Derivatives of neutral amino acids as well as of lysine and arginine have been prepared. The chloroethyl ketones are about 60% less reactive to chemical nucleophiles than the chloromethyl ketones. However, the susceptibilities of the proteases examined varied remarkably. Cathepsins B and L of the papain family of cysteine proteinases were much less susceptible (about 2 orders of magnitude less) to both peptidyl diazoethyl and chloroethyl ketones. In marked contrast, clostripain, a cysteine proteinase of a separate family was decisively more susceptible to chloroethyl ketones. The serine proteinases showed a drop in susceptibility to the chloroethyl ketones generally, and this was similar to the drop in chemical reactivity in proceeding from the chloromethyl to the chloroethyl ketone. PMID- 2930192 TI - Structural study of the sugar chains of human platelet thrombospondin. AB - The asparagine-linked sugar chains of human platelet thrombospondin were released as oligosaccharides by hydrazinolysis. About 12 mol of sugar chains was released from one thrombospondin molecule. This was converted to radioactive oligosaccharides by sodium borotritide reduction after N-acetylation, and separated into one neutral and four acidic fractions by paper electrophoresis. More than 90% of the oligosaccharides were recovered in the acidic fraction. The acidic oligosaccharides were mostly converted to neutral oligosaccharides by sialidase treatment, indicating that they are sialyl derivatives. The neutral and sialidase-treated acidic oligosaccharides were further fractionated by Bio-Gel P 4 column chromatography. Structural study of each oligosaccharide by sequential exoglycosidase digestion and methylation analysis revealed that the thrombospondin contains mono-, bi-, tri-, and tetraantennary complex-type sugar chains in addition to a small amount of high-mannose type. Approximately 70% of the complex-type sugar chains was fucosylated at asparagine-linked N acetylglucosamine residue and 19% of the biantennary complex-type sugar chains was bisected. PMID- 2930193 TI - Aspartate aminotransferase from Panicum maximum Jacq. var. trichoglume Eyles, a C4 plant: purification, molecular properties, and preparation of antibody. AB - Extracts of the leaf tissue of Panicum maximum Jacq. var. trichoglume Eyles (a phosphoenolpyruvate carboxykinase type of C4 plant) were examined and at least two isoforms of aspartate aminotransferase (EC 2.6.1.1), with different electrophoretic mobilities, were detected. The predominant isoform was purified to homogeneity from mesophyll cells. The purification procedure included fractionation with ammonium sulfate followed by chromatography on diethylaminoethyl-cellulose, Sephacryl S-300, and hydroxyapatite. The purified enzyme had specific activities of 182 and 165 mumol/min/mg protein, measured in terms of the synthesis of oxaloacetate and aspartate, respectively, at pH 8.0. The enzyme, with an apparent molecular size of 100 kDa, appears to be a dimer of a single polypeptide with a molecular size of 42 kDa. Mono specific polyclonal antibodies were raised against the 42-kDa polypeptide. Only a single stained band was detected in extracts of whole leaves by immunoblot analysis with this antibody after two-dimensional polyacrylamide electrophoresis. Furthermore, no difference in mobility was observed between the enzymes extracted from mesophyll and bundle sheath cells on native polyacrylamide gels. These findings are discussed in relation to the other isoform in the leaves of this species. PMID- 2930194 TI - Kinetic deuterium isotope effects on deamination and N-hydroxylation of cyclohexylamine by rabbit liver microsomes. AB - Deuterium isotope effects on the kinetic parameters for deamination and N hydroxylation of cyclohexylamine (CHA) catalyzed by rabbit liver microsomes with NADPH are investigated. Both reactions are inhibited by carbon monoxide and have the characteristics of typical cytochrome P450-dependent monooxygenase reactions. A small and significant deuterium isotope effect operates in the oxidative deamination of CHA. The apparent isotope effects, i.e., VH/VD and (V/K)H/(V/K)D ratios for deamination, are 1.75 and 1.8-2.3, respectively. On the basis of N hydroxylation, the VH/VD and (V/K)H/(V/K)D ratios are 0.8-0.9. The N hydroxylation rate of alpha-deuterated CHA (D-CHA) is somewhat higher than that of CHA. The increased increment of hydroxylamine formation seems to coincide with the decreased amount of deamination. Substitution of deuterium in the alpha position of CHA results in metabolic switching of cytochrome P450 from deamination to N-hydroxylation with low deuterium isotope effects. The data are interpreted in terms of an initial one-electron abstraction from the nitrogen to form an aminium cation radical followed by recombination with iron-bound hydroxyl radical leading to N-hydroxylamine, or followed by alpha-carbon deprotonation to form a neutral carbon radical. The latter can lead to a carbinolamine intermediate for deamination by way of imine or recombination with nascent iron bound hydroxyl radical. The relative rates of the reactions depend on the alpha carbon deprotonation rates of amines. PMID- 2930195 TI - Regulation of rat liver microsomal glutathione S-transferase activity by thiol/disulfide exchange. AB - The regulation of purified glutathione S-transferase from rat liver microsomes was studied by examining the effects of various sulfhydryl reagents on enzyme activity with 1-chloro-2,4-dinitrobenzene as the substrate. Diamide (4 mM), cystamine (5 mM), and N-ethylmaleimide (1 mM) increased the microsomal glutathione S-transferase activity by 3-, 2-, and 10-fold, respectively, in absence of glutathione; glutathione disulfide had no effect. In presence of glutathione, microsomal glutathione S-transferase activity was increased 10-fold by diamide (0.5 mM), but the activation of the transferase by N-ethylmaleimide or cystamine was only slightly affected by presence of glutathione. The activation of microsomal glutathione S-transferase by diamide or cystamine was reversed by the addition of dithiothreitol. Glutathione disulfide increased microsomal glutathione S-transferase activity only when membrane-bound enzyme was used. These results indicate that microsomal glutathione S-transferase activity may be regulated by reversible thiol/disulfide exchange and that mixed disulfide formation of the microsomal glutathione S-transferase with glutathione disulfide may be catalyzed enzymatically in vivo. PMID- 2930196 TI - Purification of prosthetically intact sulfite oxidase from chicken liver using a modified procedure. AB - A modified procedure was used to purify sulfite oxidase (sulfite:O2 oxidoreductase; EC 1.8.3.1) from chicken liver in high yield. The modifications included dialysis of the enzyme against a buffered solution containing sodium molybdate (prior to ion-exchange chromatography), which apparently reconstituted any demolybdo enzyme present in the extract, and phenyl-Sepharose column chromatography. Analysis showed that the purified enzyme contained Mo and heme in a 1.03:1.00 ratio, indicating that the enzyme was prosthetically intact; exogenous heme and other colored proteins were absent from the final pool. Treatment of the sulfite-reduced enzyme with 50 mM cyanide at pH 8.5 resulted in a gradual loss of catalytic activity with a half-life of 19.7 min. Analysis of the cyanide-inactivated enzyme gave a Mo:heme ratio of 1.02:1.00, providing the first direct evidence that the enzyme does not lose molybdenum when inactivated with cyanide. This modified purification procedure provides enzyme in high yield which is well-suited for experiments requiring prosthetically intact enzyme and which is not contaminated with extraneous heme or with other redox active proteins. PMID- 2930197 TI - Inositol polyphosphate production and regulation of cytosolic calcium during the biphasic activation of adrenal glomerulosa cells by angiotensin II. AB - Stimulation of aldosterone production by angiotensin II in the adrenal glomerulosa cell is mediated by increased phosphoinositide turnover and elevation of intracellular Ca2+ concentration. In cultured bovine glomerulosa cells, angiotensin II caused rapid increases in inositol-1,4,5-trisphosphate (Ins-1,4,5 P3) levels and cytosolic Ca2+ during the first minute of stimulation, when both responses peaked between 5 and 10 s and subsequently declined to above-baseline levels. In addition to this temporal correlation, the dose-response relationships of the angiotensin-induced peak increases in cytosolic Ca2+ concentrations and Ins-1,4,5-P3 levels measured at 10 s were closely similar. However, at later times (greater than 1 min) there was a secondary elevation of Ins-1,4,5-P3, paralleled by increased formation of inositol 1,3,4,5-tetrakisphosphate that was associated with cytosolic Ca2+ concentrations only slightly above the resting value. These results are consistent with the primary role of Ins-1,4,5-P3 in calcium mobilization during activation of the glomerulosa cell by angiotensin II. They also suggest that Ins-1,4,5-P3 participates in the later phase of the target cell response, possibly by acting alone or in conjunction with its phosphorylated metabolites to promote calcium entry and elevation of cytosolic Ca2+ during the sustained phase of aldosterone secretion. PMID- 2930198 TI - Biomimetic oxidation of nonphenolic lignin models by Mn(III): new observations on the oxidizability of guaiacyl and syringyl substructures. AB - Mn(III) is a one-electron oxidant, produced in vivo by the Mn peroxidases of white-rot fungi, and thought to be involved in lignin degradation by these organisms. However, Mn(III) has not been shown to oxidize the major nonphenolic substructures of lignin under mild conditions. We have used Mn(III) acetate as a biomimetic model for enzymatically generated Mn(III), and report that low concentrations of this oxidant suffice to oxidize nonphenolic lignin models at physiological temperatures and pH values. Under these conditions, the monomeric lignin model veratryl alcohol was oxidized to veratraldehyde, and the diarylpropane model 1-(3,4-dimethoxyphenyl)-2-phenylpropanol was oxidatively cleaved to veratraldehyde, 1-phenylethanol, and acetophenone. In an attempt to identify other lignin models that might be oxidized by Mn(III) more rapidly, we compared the rates at which Mn(III) was reduced by two guaiacyl models, veratryl alcohol and 1-(3-methoxy-4-isopropoxyphenyl)ethanol, vs two syringyl models, 3,4,5-trimethoxybenzyl alcohol and 1-(3,5-dimethoxy-4-isopropoxyphenyl)ethanol. The results were the opposite of those predicted: the syringyl models were oxidized slower than the guaiacyl models by Mn(III). To investigate the basis for this unexpected result, we recorded the visible absorption spectra of charge transfer complexes prepared between each of the lignin models and an electron acceptor, tetracyanoethylene or p-chloranil. The results, in general agreement with the kinetic findings, showed that the nonphenolic syringyl lignin models had higher ionization potentials than the guaiacyl models. PMID- 2930199 TI - Inhibition of glyceraldehyde-3-phosphate dehydrogenase by pentalenolactone: kinetic and mechanistic studies. AB - Incubation of rabbit muscle glyceraldehyde-3-phosphate dehydrogenase (GAPDH) with the antibiotic pentalenolactone (1) resulted in time-dependent, irreversible inhibition of GAPDH. The kinetics of inactivation were biphasic, exhibiting an initial rapid phase and a slower second phase. Pentalenolactone methyl ester (2) also irreversibly inactivated GADPH, albeit at a slower rate and with a higher KI. The substrate glyceraldehyde-3-phosphate (G-3-P) afforded protection against inactivation by 1, whereas the presence of NAD+ in the incubation mixture stimulated the inactivation by increasing the apparent affinity of the enzyme for the inhibitor. In steady-state kinetic experiments, 1 acted as a competitive inhibitor of GAPDH with respect to G-3-P but exhibited uncompetitive inhibition with respect to NAD+. Inactivation of NAD+-free apo-GAPDH by 1 showed simple pseudo-first-order kinetics. By titrating the free thiol residues of partially inactivated GAPDH, it was found that both pentalenolactone and pentalenolactone methyl ester react with all four Cys-SH residues of the tetrameric GAPDH. PMID- 2930200 TI - Damage to protein synthesis concurrent with lipid peroxidation in rat liver slices: effect of halogenated compounds, peroxides, and vitamin E1. AB - Protein synthesis and lipid peroxidation were evaluated in rat liver slices incubated in the presence of oxidants and protein synthesis inhibitors. Protein synthesis by rat liver slices was evaluated by [3H]leucine incorporation into the trichloroacetic acid (TCA)-insoluble material, and lipid peroxidation was evaluated by thiobarbituric acid-reactive substances (TBARS) released into the incubation medium. Protein synthesis inhibition by bromotrichloromethane (BrCCl3) or t-butyl hydroperoxide (t-BOOH) depended on the incubation time and oxidant concentration. [3H]Leucine incorporation was decreased to 20 and 47% of control values and TBARS were enhanced from the control value of 16.9 to 45.3 and 62.5 nmol/g of liver by incubation for 1 h with 1 mM BrCCl3 and t-BOOH, respectively. Following incubation, both protein synthesis damage and lipid peroxidation were decreased in control and oxidant-treated slices prepared from rats injected with 200 mg of DL-alpha-tocopherol/kg of body wt. Release of lactate dehydrogenase was not enhanced by oxidant treatment. Protein synthesis inhibitors reversibly decreased [3H]leucine incorporation, but the effect of oxidants on protein synthesis was irreversible. Cumene hydroperoxide and methyl ethyl ketone peroxide, but not hydrogen peroxide, damaged protein synthesis and induced lipid peroxidation. The ability of carbon tetrabromide, benzyl chloride, bromoform, bromobenzene, carbon tetrachloride, chloroform, dichloromethane, and bromochloromethane to inhibit protein synthesis was correlated with their ability to induce lipid peroxidation, and with their LD50. The results suggest that oxidant-induced lipid peroxidation and protein synthesis damage occurred concurrently, and that protein synthesis inhibition may be involved in cell injury or death mediated by free radicals. PMID- 2930201 TI - [Bestatin treatment of patients with myelodysplastic syndromes]. AB - Seven patients with myelodysplastic syndromes (M-DS) were treated with 30 mg Bestatin daily. Six of the patients (85.7%) responded. Clonogenic bone marrow cell culture studies in the patients have demonstrated intrinsic hemopoietic stem cell and progenitor cell abnormalities. After Bestatin treatment, these abnormalities involved in differentiation and maturation of hematopoietic progenitors were markedly improved and resulted in the improvement of hematological findings in responders. Addition to the culture system of Bestatin at a concentration of 0.01 microgram/ml and 1 microgram/ml enhanced CD4 positive T cell colony formation without enhancing CFU-GM and CFU-GEMM. These results suggest that the effects on hematopoiesis of Bestatin may be mediated by T cells, not by direct action of the drug. PMID- 2930202 TI - [Polarographic analysis of tumor tissue oxygen tension after hyperthermia combined with misonidazole]. AB - For the purpose to analyse the influence of a thermosensitizing drug, misonidazole (MIS), on tissue oxygen tension (TpO2), TpO2 in human gastric cancer tissue (H-23) was measured by a polarographic method. MIS, 500 mg/kg, was given i.p. and then the heat treatment was done in a water bath at 43.5 +/- 0.1 degrees C for 23 minutes. A second treatment was performed to develop thermotolerance at the following intervals: 24 hours, 72 hours, 5 days, and 7 days. Tumor doubling time was shortest at 72-hour interval, i.e., the maximal thermotolerance of the tumor developed at 72-hour interval, whereas the tumor doubling time in case of combined use of MIS was shortest at 24-hour interval. TpO2 in the 72-hour interval treatment decreased soon after hyperthermia, and returned to a pre heated value 3 hours after, whereas in the other 3 treatments the recovery time was 6 to 12 hours. On the other hand, in 24-hour interval of the combined use of MIS, the post-thermal value of TpO2 was about a half of the pre-thermal value and recovered 24 hours after. In the 5- and 7-day interval treatments, TpO2 declined notably and did not return to the pre-thermal value during 24 hours. These data suggest that the thermo-sensitizing effects of MIS were brought about by prolonged and extreme decrease in TpO2. PMID- 2930203 TI - [Effect of sodium thiosulfate on the antitumor effect and nephrotoxicity of CDDP in human gastric cancer transplanted in nude mice]. AB - Sodium thiosulfate (STS) is known to decrease the nephrotoxicity of cisplatin (CDDP). CDDP has been recognized effective in some type of gastric cancers, and there has been an attempt to examine the optimal dose of STS, which suppresses the CDDP-induced nephrotoxicity without interfering its anticancer effect. The gastric cancer cell lines (KATO-III and MKN 45) were transplanted into BALB/c nu/nu mice. CDDP was injected intraperitoneally once a week 5 times with various doses of STS, and the effects of STS on the antitumor effect as well as the nephrotoxicity of CDDP were examined. The antitumor effect of CDDP (9 mg/kg) was suppressed by 30% with the simultaneous injection of 372 mg/kg (50 fold-molar radio of STS to CDDP) and abolished by 1,488 mg/kg (200 fold-molar radio) of STS. The elevated serum BUN and the kidney content of platinum following CDDP administration were at the normal ranges in the nude mice received these doses of STS. Also, the atrophic and regenerative changes of the kidney tubules induced by CDDP were scarcely observed in these nude mice. From these results, only 50 fold molar radio of STS to CDDP suppresses the nephrotoxicity of CDDP without interfering its antitumor effect, and this rather smaller amounts of STS is considered to be optimal. Further studies, however, will be needed for clinical application. PMID- 2930204 TI - [Antitumor effect of a new anthracycline derivative, MX2, against human glioma cells]. AB - A new morpholino anthracycline derivative, MX2, has a potent antitumor activity similar to adriamycin. Because of high lipid solubility of MX2 (log P = 2.84, pH 7.4), the compound can cross the blood-brain barrier easier than adriamycin. In this study we tested the anti-tumor activity of MX2 against human glioma in vitro and in vivo. MX2 showed a marked cytocidal effect against U105MG, U251MG, U373MG and KMG4 cells when more than 30 ng/ml was added in the medium. Although the sensitivity against MX2 differed depending on the cell lines, the cytocidal effect of MX2 was similar to adriamycin. The colony formation of KMG4 cells was markedly inhibited by MX2 dose-dependently. The growth of KMG4 cells inoculated subcutaneously into nude mice was inhibited by the intraperitoneal administration of MX2 4 or 1.3 mg/kg. These results suggest that MX2 seemed to be useful in the treatment of malignant glioma. PMID- 2930205 TI - [Changes of protein and RNA content in accumulated G1 cells by delta12-PGJ2]. AB - Protein and RNA content in accumulated G1 cells was measured with B16 melanoma cells by flow cytometer to study the mechanism of antineoplastic action of delta 12PGJ2. DNA histogram showed that, after a 6 hr exposure to delta 12PGJ2, the percentage of tumor cells in G2M phase increased, and G1 accumulation with depletion of cell population in S phase was seen after 12-24 hr exposure to 2.0 micrograms/ml of delta 12 PGJ2. Protein content in accumulated G1 cells increased at 6 hr after exposure, and subsequently decreased. However, the protein content treated with delta 12PGJ2 was higher than that of the control. A reduction of RNA content in G1 cells was seen after delta 12PGJ2 exposure. As the result, it was found that delta 12PGJ2 made cell progression ceased in G1 phase of cell cycle, and where protein and RNA content was higher than that of control. It is suggested that some hyper-metabolite state was caused by delta 12 PGJ2 in cultured B16 melanoma cells. PMID- 2930206 TI - [Investigation on the adequate administration interval with OK-432, using the cytotoxicity test]. PMID- 2930207 TI - Inhibition of allergic contact dermatitis and ultraviolet radiation-induced tissue swelling in the mouse by topical amiloride. AB - Amiloride is known to inhibit membrane sodium transport and has been shown in vitro to inhibit cell activation and proliferation in several model systems. These effects occur at relatively high local concentrations of amiloride. We studied the cutaneous response to the topical application of amiloride hydrochloride. Our observations demonstrated that topical application of amiloride was potent in its ability to inhibit murine tissue swelling and inflammation in response to contact sensitizing agents and ultraviolet radiation. These observations might suggest a role for amiloride or its analogues as topical anti-inflammatory or antiproliferative drugs. PMID- 2930208 TI - Cyclosporine in the treatment of psoriatic arthritis. AB - The short-term efficacy of cyclosporine in the treatment of six patients with moderately severe to severe psoriatic arthritis was evaluated in an open study. Patients received oral cyclosporine (6 mg/kg/d) for eight weeks. In all patients, significant improvement of psoriasis was noted within two to four weeks. At the end of therapy, rheumatologic assessment revealed the following trends in disease activity: a decrease in the number of tender joints, joint tenderness index, duration of morning stiffness, and an increase in grip strength. There was a decrease in the number of swollen joints, joint swelling index, and the time taken to walk 50 ft. Overall disease activity significantly improved as assessed independently by the patient and physician. For psoriasis and psoriatic arthritis, disease activity worsened toward baseline within four weeks of discontinuation of therapy. Short-term, low-dose cyclosporine therapy may be effective in treating psoriasis and psoriatic arthritis. PMID- 2930209 TI - Pseudocyst of the auricle associated with trauma. AB - A pseudocyst of the auricle (benign idiopathic cystic chondromalacia) is an intracartilaginous cystic swelling of the anterior auricle. The cause is uncertain, and most patients deny any history of inflammation or trauma. A patient had antecedent trauma and a fracture in the conchal cartilage; a simple surgical procedure was used to treat this patient. PMID- 2930210 TI - Segmented heterochromia in black scalp hair associated with iron-deficiency anemia. Canities segmentata sideropaenica. AB - A newly recognized disorder of black scalp hair is characterized by the irregularly alternating segmentation of hair into dark and light bands. A 15-year old girl had segmented heterochromic scalp hair in association with iron deficiency anemia. The clinical and laboratory investigations support the view that low serum iron levels play a critical role in reducing eumelanogenesis and in the possible failure of melanin transfer. The segmented heterochromic hair recovered completely after iron supplementation, which coincided with increased eumelanogenesis in the recovered hair. This clinical experience indicated participation of iron in the kinetics of melanogenesis within the follicular melanocytes. PMID- 2930211 TI - Pigmented breast carcinoma. A clinical and histopathologic simulator of malignant melanoma. AB - A case of infiltrating breast carcinoma presenting as a pigmented lesion of the areola and nipple is described. The pigmentation was found to be primarily due to interspersed melanocytes and melanophages within the tumor. The histologic criteria and the differential immunohistochemical staining characteristics of melanoma and breast carcinoma are presented. Also emphasized is the difficulty in differentiating pagetoid malignant melanoma and epidermotrophic breast carcinoma. PMID- 2930212 TI - A young woman with nodules on her face and trunk. Tertiary (tubercular) syphilis. PMID- 2930213 TI - Multisystem crystalline deposits. Primary hyperoxaluria. PMID- 2930214 TI - Dysplastic anxiety. PMID- 2930215 TI - Is photography necessary in following up patients with dysplastic nevi? PMID- 2930216 TI - Total-body photographs of dysplastic nevi: who pays? PMID- 2930217 TI - Total body photographs of dysplastic nevi. PMID- 2930218 TI - Physician-drug company complex. PMID- 2930219 TI - Intractable atopic eczema suggests major affective disorder: poor parenting is secondary. PMID- 2930220 TI - Topical cyclosporine and contact dermatitis in guinea pig and man. PMID- 2930221 TI - Double-blind randomized placebo-controlled trial of local cyclosporine in atopic dermatitis. PMID- 2930222 TI - Allergic contact dermatitis to a nasal cannula. PMID- 2930223 TI - Is minoxidil (Rogaine) clinically effective? PMID- 2930224 TI - Congenital myotonic dystrophy: respiratory function at birth determines survival. AB - The clinical features of 14 neonates with congenital myotonic dystrophy were retrospectively reviewed. These babies represent all the new cases of congenital myotonic dystrophy seen in this department since 1982. Twelve babies were referred because of either difficulties in diagnosis or difficulties in the management of their respiratory problems. Of the 14 babies, 13 had birth asphyxia, 11 were premature, and four had intrauterine growth retardation. Ten babies required artificial ventilation from birth. Abnormalities on chest radiography included thin ribs (n =9) and raised right hemidiaphragms (n = 5). Recurrent episodes of collapse and consolidation of the lungs secondary to poor swallowing occurred in all ventilated babies. All babies ventilated for longer than four weeks died of respiratory complications before the age of 15 months. One baby was successfully extubated after diaphragmatic plication, but he died a few months later. Duration of ventilation was the best guide to prognosis. PMID- 2930225 TI - Cardiac rhabdomyomata in tuberous sclerosis: their course and diagnostic value. AB - Echocardiography was performed in 60 people with tuberous sclerosis to ascertain the prevalence and course of cardiac rhabdomyomata at different ages. Twenty five (58%) of 43 children had tumours, but only three (18%) of 17 adults. The tumours tended to remain the same size through childhood. Only three infants were included but evidence from this and some published case reports suggest that the tumours tend to regress in early infancy and again in adolescence. The prevalence of tumours in young infants with tuberous sclerosis is likely to be considerably above 50%. As other signs of tuberous sclerosis are usually absent at this age echocardiography may afford the most useful diagnostic test in early infancy. PMID- 2930226 TI - The range of neural tube defects in southern India. AB - During a prospective study of 3500 consecutive births from November 1985 to January 1987 at three hospitals, 40 babies were found to have neural tube defects, an extremely high incidence (11.4/1000 births). The defects comprised anencephaly (n = 18), meningomyelocele (n = 11), Arnold-Chiari deformity (n = 3), encephalocele (n = 3), iniencephaly (n = 2), and one each of occipital meningocele, spina bifida occulta, and anencephaly with rachischisis. There were significant differences in incidence between those with consanguineous and nonconsanguineous parents and those whose mothers had previously given birth to malformed infants or who had had miscarriages, and those who had not. Significantly more defects were found among stillborn and low birthweight babies, among girls, and among those whose mothers were aged between 20 and 30 years. Just over a third (14) were breech presentations, and hydramnios was present in 16 (40%). PMID- 2930227 TI - Prognosis of extrahepatic biliary atresia. AB - We carried out a retrospective investigation of the 89 patients with extrahepatic biliary atresia born in The Netherlands during a 10 year period. Of these 89 patients 10 had a diagnostic laparotomy only. Eight patients had an anastomosis between the proximal bile duct and the intestine, and the remaining 71 had hepatic portoenterostomies. Bile drainage was re-established in 46 (65%). After successful hepatic portoenterostomy the development of cholangitis was the most important determinant of long term survival; five year survival was 54% in the 19 patients who had cholangitis and 91% in the 27 who did not. In the whole group of 71 patients the five year survival was 47%. Seventeen patients were at least 5 years of age at the time of writing, three of whom had had liver transplantation. Three patients have cirrhosis and hyperbilirubinaemia, and the other 11 have normal bilirubin concentrations and normal or slightly raised transaminase activities. To improve these results early surgical intervention in all children with extrahepatic biliary atresia is necessary, as are better methods of prophylaxis and treatment of cholangitis. PMID- 2930228 TI - Sodium transport in erythrocytes: differences between normal children and children with primary and secondary hypertension. AB - The following measurements were made in normal children, children with primary hypertension, and children with secondary hypertension: erythrocyte intracellular sodium concentration, total sodium efflux rate constant, and maximum binding of ouabain to erythrocytes reflecting the number of sodium/potassium adenosine triphosphatase pump sites. Children with primary hypertension had a significantly higher mean erythrocyte intracellular sodium concentration (8.2 compared with 6.6 and 6.7 mmol/l cells), and significantly lower total sodium efflux rate constant (0.5071 compared with 0.6983 and 0.6197) and maximum binding of ouabain to erythrocytes (9.1 compared with 11.7 and 11.0 nmol/l cells) than normal children and children with secondary hypertension, respectively. PMID- 2930229 TI - Behaviour in first year after drug dependent pregnancy. AB - Neurobehavioural development of a group of 35 infants of drug dependent mothers and of a reference group of 37 infants was compared. Two tailed testing showed that at the age of 3 months the infants of drug dependent mothers seemed to be more active than the reference group; at 6 months, however, no difference was found. On the infant behaviour temperament questionnaire, infants of drug dependent mothers tended to have slightly better scores for 'duration of orienting' at the age of 9 months; five other dimensions of behaviour did not differ between the groups. The Bayley scales of infant development and neurological examination according to the method of Touwen did not show any significant differences among the groups at the ages of 6 or 12 months. At 12 months infants of drug dependent mothers had slightly but not significantly worse results on electroencephalography. Studied with multidisciplinary measurements, the development of infants of drug dependent mothers does not seem to diverge particularly from the development of the reference group. PMID- 2930230 TI - Standards for the predictive accuracy of short term body height and lower leg length measurements on half annual growth rates. AB - Determinations of body height and calculations of growth velocity are still the major parameters for the assessment of normal and aberrant growth. The present study was performed to investigate the minimum time interval between consecutive measurements that is necessary for a statement on significant length increment both of total body height and lower leg length. We present standards for the predictive accuracy of short term measurements for the prediction of the conventional half annual growth rate. We also provide centiles of the predictive error that occurs when the difference between two consecutive measurements is used to determine a half annual growth rate. PMID- 2930231 TI - Sleep phase and gastro-oesophageal reflux in infants at possible risk of SIDS. AB - The association between gastro-oesophageal reflux and sleep state in 24 infants with confirmed or suspected gastro-oesophageal reflux was studied by monitoring both the pH in the lower oesophagus and polygraphic tracings made during sleep at night. Gastro-oesophageal reflux during the night was confirmed in 20 infants. Three hundred and sixteen precipitous drops of more than one unit of pH were recorded during the studies, 186 during periods of wakefulness. Of 130 drops in pH during sleep, 62 (48%) began during active sleep and 62 during indeterminate sleep. Of the latter, 56 (90%) were associated with brief gross body movements. Only five of the drops in pH (4%) began during quiet sleep. Gastro-oesophageal reflux stopped during active sleep on 56 occasions (43%), in indeterminate sleep in 62 (47%), and in quiet sleep in 12 (9%). Episodes of gastro-oesophageal reflux starting or ending in quiet sleep were uncommon. The occurrence of gastro oesophageal reflux during active sleep may partly explain why reflux during sleep is a risk factor for pulmonary disease. PMID- 2930232 TI - Early hyperkalaemia in very low birthweight infants in the absence of oliguria. AB - We reviewed 1552 admissions to a neonatal intensive care programme; seven, all with a birth weight less than 1500 g, developed early onset, non-oliguric hyperkalaemia (potassium concentration greater than 7.0 mmol/l). Although their perinatal variables were similar to those of a normokalaemic group, hyperkalaemic infants had a higher incidence of intraventricular haemorrhage and developed increased concentrations of plasma creatinine by 7 days of age. PMID- 2930233 TI - Twinning rates and social class in Great Britain. AB - We examined like and unlike sex twinning rates in Great Britain by social class over the period 1974-85. Although twinning rates are believed to have changed over that period, we found no evidence of differential change by social class, suggesting that any factors affecting twinning are widespread in the population. PMID- 2930234 TI - Resident parents and shorter hospital stay. AB - A total of 586 admissions for 12 medical conditions were reviewed. The stay of children accompanied by a resident parent was 31% shorter than those whose parents were not resident. Resident parents benefit the emotional well being of the child and increase hospital efficiency; accommodation for parents should therefore be an integral part of a unit admitting children. PMID- 2930235 TI - Transient tachypnoea of the newborn and asthma. AB - A total of 58 children aged 4-5 years who were diagnosed as having transient tachypnoea of the newborn were studied. In contrast with the control group (n = 58), the infants with transient tachypnoea of the newborn had a significantly higher incidence of recurrent (more than two) episodes of wheezy breathlessness, symptoms consistent with asthma, and signs consistent with atopy. PMID- 2930236 TI - Evaluation of two combined oxygen and carbon dioxide transcutaneous sensors. AB - Two combined oxygen and carbon dioxide electrodes were assessed in neonates, infants, and children up to 16 years. They were convenient to use and the measurement error for PtcCO2 was acceptable. In both models, however, the PtcO2 electrode had a reduced performance compared with a single electrode. PMID- 2930237 TI - Paediatric dialectics in a BPA triennium 1985-1988. PMID- 2930238 TI - Reflex anal dilatation associated with severe chronic constipation. PMID- 2930239 TI - Reflex anal dilatation and sexual abuse. PMID- 2930240 TI - Urinary creatinine excretion in the newborn. PMID- 2930241 TI - Rubella immunisation. PMID- 2930242 TI - '...officiously to keep alive'. PMID- 2930243 TI - Sweat tests and flucloxacillin. PMID- 2930244 TI - Rising asthma admissions and self referral. PMID- 2930245 TI - Chemical composition of bottled mineral water. AB - Thirty-seven brands of domestic and imported mineral waters were analyzed for the following: alkalinity, aluminum, barium, beryllium, boron, cadmium, calcium, chloride, chromium, cobalt, copper, fluoride, iron, lead, lithium, magnesium, manganese, mercury, molybdenum, nickel, nitrate, pH, phosphate, potassium, silver, sodium, specific conductance, sulfate, tin, vanadium, and zinc. Of the waters examined in this study, 24 had one or more determinands that were not in compliance with the drinking water standards in the United States. PMID- 2930246 TI - Illness and absenteeism among California highway patrol officers responding to hazardous material spills. AB - Highway patrol officers are the primary responders to hazardous material spills in California, yet little is known regarding the health effects resulting from this exposure. A historical cohort study of 993 California highway patrol officers who responded to hazardous material spills in 1984 was conducted. The records of officers who were exposed to acutely toxic chemicals were followed for the subsequent week to determine if they demonstrated more absenteeism or illness compared to officers who were not exposed to toxic chemicals. No significant differences in the frequency of absenteeism or illness was found between the two groups during the week following exposure. No indication was found that exposure to hazardous materials during a highway patrol spill response results in increased absenteeism. PMID- 2930247 TI - Toxic pollutants, science, and corporate influence. PMID- 2930248 TI - Cancer mortality in U.S. counties with hazardous waste sites and ground water pollution. AB - Since the late 1950s, more than 750 million tons of toxic chemical wastes have been discarded in an estimated 30,000 to 50,000 hazardous waste sites (HWSs). Uncontrolled discarding of chemical wastes creates the potential for risks to human health. Utilizing the National Priorities Listing (NPL) of hazardous waste sites developed by the United States Environmental Protection Agency (EPA), this study identified 593 waste sites in 339 U.S. counties in 49 states with analytical evidence of contaminated ground drinking water providing a sole source water supply. For each identified county, age-adjusted, site-specific cancer mortality rates for 13 major sites for the decade 1970-1979, for white males and females, were extracted from U.S. Cancer Mortality and Trends 1950-1979. Also, HWS and non-HWS counties that showed excess numbers of deaths were enumerated for each cancer selected. Significant associations (p less than .002) between excess deaths and all HWS counties were shown for cancers of the lung, bladder, esophagus, stomach, large intestine, and rectum for white males; and for cancers of the lung, breast, bladder, stomach, large intestine, and rectum for white females when compared to all non-HWS counties. There were no consistent geographical patterns that suggested a broad distribution of gastrointestinal cancers associated with HWSs throughout the United States, although we did identify a cluster of excess gastrointestinal cancers in counties within states located in EPA Region 3 (Delaware, Maryland, Pennsylvania, Virginia, West Virginia).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2930249 TI - Health status of anthracite surface coal miners. AB - In 1984-1985, medical examinations consisting of a chest radiograph, spirometry test, and questionnaire on work history, respiratory symptoms, and smoking history were administered to 1,061 white males who were employed at 31 coal cleaning plants and strip coal mines in the anthracite coal region of northeastern Pennsylvania. The prevalence of radiographic evidence of International Labour Office (ILO) category 1 or higher small opacities was 4.5% in 516 men who had never been employed in a dusty job other than in surface coal mining. Among these 516 workers, all 4 cases of ILO radiographic category 2 or 3 rounded opacities and 1 case of large opacities had been employed as a highwall drill operator or helper. The prevalence of category 1 or higher opacities increased with tenure as a highwall drill operator or helper (2.7% for 0 y, 6.5% for 1-9 yr, 25.0% for 10-19 y, and 55.6% for greater than or equal to 20 y drilling). Radiographic evidence of small rounded opacities, dyspnea, and decreases in FEV1.0, FVC, and peak flow were significantly related to tenure at drilling operations after adjusting for age, height, cigarette smoking status, and exposures in dusty jobs other than in surface coal mining. However, tenure in coal cleansing plants and other surface coal mine jobs were not related to significant health effects. The apparent excess prevalence of radiographic small rounded opacities in anthracite surface coal mine drillers suggests that quartz exposures have been increased. Average respirable quartz concentrations at surface coal mine drilling operations should be evaluated to determine whether exposures are within existing standards, and dust exposures should be controlled. PMID- 2930252 TI - You don't have to be sick to get better. PMID- 2930251 TI - Mortality among forest and soil conservationists. AB - The mortality of forest conservationists and soil conservationists in the United States Department of Agriculture (USDA) who died during January 1, 1970-December 31, 1979 (N = 1,411 white males) while actively employed or while receiving a pension was evaluated. The proportionate mortality analysis was used to identify cancers that might be elevated in this occupational group compared to the total U.S. white male population, whereas case-control analyses more rigorously evaluated the disease association with occupation. Controls were selected from employees at USDA who died of any cause of death other than that cause of death represented by the case. In case-control analyses, non-Hodgkin's lymphoma (NHL) and colon cancer demonstrated a statistically significant linear trend (p less than .05) with duration of employment as either a forest or soil conservationist, which suggests an occupational etiology for both diseases. Soil conservationists who were last employed after 1960 experienced significantly elevated risks for NHL (OR = 2.6) and colon cancer (OR = 1.8), whereas those last employed before 1960 were not at an increased risk. Among forest conservationists, the risk for both NHL and colon cancer appeared to be elevated before and after 1960. PMID- 2930250 TI - Effects of low-level carbon monoxide exposure on resting and exercise-induced ventricular arrhythmias in patients with coronary artery disease and no baseline ectopy. AB - The effects of acute elevation of carboxyhemoglobin (COHb) concentrations on resting and exercise-induced ventricular arrhythmias were evaluated in 10 patients who had ischemic heart disease and in whom no ectopy during baseline monitoring was noted. After an initial training session, patients were exposed to air, 100 ppm carbon monoxide (CO), or 200 ppm CO on successive days in a randomized, double-blind, cross-over fashion. After exposure to 100 and 200 ppm CO, venous COHb levels averaged 4% and 6%, respectively. Symptom-limited supine exercise was performed after exposure. Eight of the 10 patients had evidence of exercise-induced ischemia--either angina, 1.0 mm ST depression, or abnormal ejection fraction response--during 1 or more exposure days. Ambulatory electrocardiograms were obtained on each day and analyzed for arrhythmia frequency and severity. On air and CO exposure days, each patient had only 0-1 ventricular premature beat/h in the 2 h prior to exposure, during the exposure period, during the subsequent exercise test, and in the 5 h following exercise. In conclusion, low-level CO exposure is not arrhythmogenic in patients with coronary artery disease and no ventricular ectopy at baseline. PMID- 2930253 TI - Closing the gap between grand theory and mental health practice with families. Part 1: The framework of systemic organization for nursing of families and family members. AB - This paper proposes a nursing framework for individuals and families that was inductively derived from existing knowledge and the author's personal experience. The framework is based on the premise that all things are organized as systems. Individuals, family systems, and the environment are interrelated and the congruence of patterns and rhythms between systems and subsystems signifies health. Nursing involves assisting individuals and families to reduce anxiety by weighing against each other the two major dimensions of system control and congruence or spirituality with the aim of maintaining a dynamic equilibrium. PMID- 2930254 TI - Closing the gap between grand theory and mental health practice with families. Part 2: The control-congruence model for mental health nursing of families. AB - The control-congruence model is based on the framework of systemic organization and presents a mental health nursing approach to families with physical, emotional, interpersonal, social, or environmental problems. Special instruments are available to assess and evaluate family functioning. The model distinguishes itself by encouraging self-diagnosis, strengthening effective family behaviors already practiced, and introducing new behaviors in tune with the family's usual patterns. The model allows flexibility for nurses to reach families through practicing the art of nursing. PMID- 2930255 TI - Vietnam: resolving the death of a loved one. AB - This article is based on a study to explore the grief experience of individuals who suffered the loss of a family member in the Vietnam war. A phenomenologic approach was used to understand the grief experience of five family members of Vietnam casualties. A convenience sample of five subjects was used. Data for this study were obtained through an open-ended interview conducted by the researcher in the home of each subject. The method of analysis of the phenomenologic data was based on Giorgi's (1975) model. The researcher modified this method to identify patterns and themes in the interviews. The grief experiences of the family members emerged as prolonged early phases of the grief process. The patterns identified were prolonged early phases of denial and anger. The significant themes identified were (a) denial and a sense of unreality, (b) anger, (c) isolation, (d) sadness, (e) frustration, and (f) ambivalence. Qualitative data from a sample of five subjects cannot be generalized to the population of all family members of Vietnam casualties, but it is significant and genuine for these subjects. The data suggest that the circumstances of the death, the lack of concrete evidence, the inadequate support available, and the conflicted social environment all contributed to the prolonged early grief phases and the struggle experienced by these family members to resolve their loss. PMID- 2930256 TI - A descriptive study of seclusion: the unit environment, patient behavior, and nursing interventions. AB - The purpose of this descriptive study was to identify unit environmental factors at the initiation of seclusion, and patient behavior and nursing interventions throughout seclusion. The convenience sample of 56 seclusion incidents included 43 patients. A peak time for seclusion to be initiated was within 24 hours of admission. Before seclusion most behaviors were disturbed but nonviolent; during seclusion most behaviors were nondisturbed. Variables studied did not indicate that units were more disturbed when seclusions were initiated than at other times. Seclusion was generally used in conjunction with other interventions. PMID- 2930257 TI - Mothers' perceptions of incest: sustained disruption and turmoil. AB - Eleven mothers whose daughters had allegedly been sexually abused by the father or father figure were interviewed to evaluate their perceptions of the sexual abuse. Subjects were obtained from a caseload of a county Department of Family and Child Protective Services. Ages ranged from 5 to 17 years and both black and white children were represented. Content analysis was used to analyze the data and revealed that the mothers in the sample continued to experience turmoil in their lives long after disclosure of the abuse occurred. These mothers were unable to consistently protect their daughters or reconstruct their family lives after the incest was disclosed. PMID- 2930258 TI - The Victim Care Service: a program for victims of sexual assault. AB - Sexual victimization is a singularly traumatic event. At times, however, the implicit danger of the trauma experience itself gets exaggerated. For the victim the more lasting damage frequently stems from how he or she was treated by friends, family, health care providers, and public authorities following the incident. Treating the victimized patient as quickly and sensitively as possible is essential to minimizing the potential for further victimization. The Emergency Department at Boston City Hospital is frequently the site for the acute management of sexual assault victims. The Victim Care Service is designed to prevent secondary traumatization of such victims. The five-phase program and the fundamental assumptions upon which the phases are based are presented. PMID- 2930260 TI - Children of alcoholics. An emerging mental health issue. PMID- 2930259 TI - New directions for psychiatric mental health nurses: the chronically mentally ill elderly. PMID- 2930261 TI - [Imprint cytology in the diagnosis of tumors of the thyroid]. AB - We have correlated imprint cytology findings in thyroid tumors to the results of preoperative fine needle aspiration and operative specimen histology. Specificity of imprint cytology proved greater than that of fine needle aspiration cytology and topographic correlations were particularly helpful. Imprint cytology can improve the intraoperative histologic diagnosis. Because abundant cells are available, imprint thyroid cytology is ideal for teaching and training cytologists. Imprint cytology provides enough cells to perform special techniques, such as quantitative cytology, that are useful for the diagnosis of some tumor varieties (e.g. follicular tumors). PMID- 2930262 TI - Handedness and deformities, radiographic changes, and function of the hand in rheumatoid arthritis. AB - The correlation of handedness with deformities, radiographic changes, and function of the hand was studied in a large group of patients with rheumatoid arthritis and a dominant right hand. There was no significant difference in the proportion of patients who had swan neck deformity, boutonniere deformity, uncorrectable ulnar deviation, and flexor tenosynovitis in the dominant and non dominant hands. There were significantly greater radiological changes in the dominant hand, however, and the middle and index fingers were most severely affected. The severe involvement of these fingers may be related to their greater use in daily activities. There was also more severe functional impairment in the dominant hand. PMID- 2930263 TI - Raised serum IgG and IgA antibodies to mycobacterial antigens in rheumatoid arthritis. AB - Autoantigens cross reactive with mycobacteria are implicated in the pathogenesis of adjuvant arthritis in the rat, and there are reports of changes in the immune response to mycobacteria in human rheumatoid arthritis (RA). We have therefore examined the IgM, IgG, and IgA antibody levels to crude mycobacterial antigens and to two recombinant mycobacterial heat shock/stress proteins (65 kD and 71 kD) in sera from patients with RA, systemic lupus erythematosus (SLE), and Crohn's disease, and from healthy controls. IgA binding to the crude mycobacterial antigens was significantly raised in RA sera, though IgG and IgM binding tended to be lower than in controls. Both IgA and IgG binding to the heat shock proteins were significantly raised in the RA sera. Smaller significant rises in both classes were seen in sera from patients with SLE, and in the IgA class only to the 65 kD protein in Crohn's disease. The rises in IgG and IgA antibodies to the 65 kD protein in RA were significantly higher than in the other diseases, however. It is interesting that this protein is the one responsible for adjuvant arthritis in the rat. PMID- 2930264 TI - Post-yersinial arthritis in Cleveland, England. AB - Four cases of post-yersinial reactive arthritis are described. All patients presented with an acute lower limb arthropathy with features of an associated enthesopathy. Two patients had restriction of axial skeletal movements. Systemic features were prominent in three, including weight loss and malaise. Mean age of onset was 34 years. Three patients gave a history of antecedent diarrhoea within the previous month. Three patients had raised titres to Y enterocolitica type 0:3 (ranging from 1 in 320 to 1 in 2560) and one had raised titres to Y pseudotuberculosis type 2 at 1 in 640. Two of the three patients with Y enterocolitica reactive arthritis ran a chronic course with low grade arthropathy of lower limbs and back stiffness. One patient developed radiological sacroiliitis at two years, and two patients had an increased sacroiliac index, though x rays of the sacroiliac joints were normal. The patient with Y pseudotuberculosis reactive arthritis had a self limiting disease with spontaneous resolution over six months. PMID- 2930266 TI - An experimental animal model of Kashin-Beck disease. AB - Twelve young macaque monkeys were fed with grain and water from areas actively endemic or non-endemic for Kashin-Beck disease. Both dietary grain and water from geographical areas endemic for Kashin-Beck disease induced a sequence of pathological changes in the growth plates and articular cartilage and biochemical changes in the serum and urine of monkeys. These changes are similar to those in human Kashin-Beck disease. It is considered that this may be a simple and valuable model for the further study of this disease and its management and control. The results suggest that the pathogenetic factors of Kashin-Beck disease relate both to grain and to water in the diet in endemic areas. The experiment also shows that certain serum enzyme concentrations correlate with chondronecrosis. PMID- 2930265 TI - Specific accumulation of technetium-99m radiolabelled, negative liposomes in the inflamed paws of rats with adjuvant induced arthritis: effect of liposome size. AB - Technetium-99m labelled, negatively charged liposomes accumulate in the inflamed tissue of rats with adjuvant induced arthritis. Up to 10 times more liposome accumulation was seen in inflamed paws than in paws of control rats, and this represented 5.3% of the injected liposome dose. The accumulation of liposomes in inflamed tissue was directly related to the liposome size, the maximal accumulation occurring with liposomes less than 100 nm in diameter. PMID- 2930267 TI - Transverse myelitis occurring during pregnancy in a patient with systemic lupus erythematosus. AB - Myelopathy is a well recognised but infrequent neurological manifestation of systemic lupus erythematosus (SLE). The case of a 27 year old woman with SLE of seven years' duration who developed a spastic paraparesis during her second pregnancy is reported. Magnetic resonance imaging did not show any intrinsic abnormality of the spinal cord. Anticardiolipin antibody was weakly positive and C4 was low. The patient responded dramatically to steroids. PMID- 2930268 TI - Chronic synovitis of the shoulder in familial Mediterranean fever: a disease of symptoms not signs. AB - Severe shoulder pain in a 41 year old Arab woman persisted for three months despite non-steroidal anti-inflammatory drug treatment. Isotope bone scanning and computed tomography showed inflammation of the glenohumeral joint and a large effusion, which needle aspiration had initially failed to reveal. A diagnosis of familial Mediterranean fever was made on the basis of a strongly suggestive past personal and family history, sterility of the joint effusion, and a good response to colchicine. PMID- 2930269 TI - Spontaneous atlantoaxial subluxation: an unusual presenting manifestation of Reiter's syndrome. AB - A male Sikh presented with spontaneous neck pain. Plain cervical radiography showed gross atlantoaxial subluxation (AAS). Computed tomography showed soft tissue anterior to a subluxed odontoid peg. A diagnosis of atlantoaxial tuberculosis was considered. Confirmation of this would have required a trans oral anterior cervical biopsy. Despite the paucity of other rheumatic symptoms a diagnosis of Reiter's syndrome with spondylitis was made, and the only surgical procedure required was posterior fusion of C1 and C2, with resultant spinal stability and pain relief. This is the first report of Reiter's syndrome presenting with AAS. PMID- 2930270 TI - Benign outcome of hypertensive renal crisis in scleroderma. PMID- 2930271 TI - Immunisation triggering rheumatoid arthritis? PMID- 2930272 TI - Lymphoma chemotherapy as remission inducing treatment in rheumatoid arthritis. PMID- 2930273 TI - Effect of high tibial osteotomy on upper tibial venous drainage: study by intraosseous phlebography in primary osteoarthritis of knee joint. AB - The effect of high tibial osteotomy on the upper tibial venous pattern in primary painful osteoarthritis of the knee joint was studied by preoperative and three to six months postoperative intraosseous phlebograms. The normal phlebographic pattern was established by phlebograms in five patients with normal knees. The preoperative engorgement, tortuosity of the medullary sinusoids, and slow dye clearance showed a remarkable conversion to a near normal appearance after the operation. Rest pain disappeared in all patients after the osteotomy, suggesting that venous congestion is the cause of 'rest pain'. PMID- 2930274 TI - Development of a new radiographic scoring system using digital image analysis. AB - A scoring system using computerised analysis of digital stored images of knee radiographs has been developed. Measurement is based on the assessment of joint space size. It is sensitive, rapid, and reproducible. Plain radiographs are positioned on an acetate grid; a computer generated grid is superimposed on a digital image of the radiograph viewed on a closed circuit television monitor and the joint space measured automatically. Area and distance have been assessed; area measurements are more reproducible. Application of microcomputer based digital image analysis to radiological scoring systems is an important step in understanding the nature and progression of arthritis. PMID- 2930275 TI - Anti-IgE autoantibodies in systemic sclerosis (scleroderma). AB - An enzyme immunoassay was used to determine the prevalence of anti-IgE auto antibodies in 66 patients with systemic sclerosis (scleroderma) stratified according to extent and duration of disease. Serum IgG anti-IgE antibodies were detected in 14 (21%) patients and IgM anti-IgE antibodies in nine (14%) patients. The overall prevalence of IgG or IgM isotypes was 21/66, (32%). Anti-IgE autoantibodies were not found in six patients with undifferentiated connective tissue disease or two patients with eosinophilic fasciitis. Attempts to demonstrate histamine release from basophils in vitro by using serum samples containing high titre anti-IgE antibody were unsuccessful. By multivariate analysis the presence of anti-IgE antibody was not associated with duration of systemic sclerosis; extent of scleroderma; specific visceral features, including heart, lung, renal, and gastrointestinal involvement; or mortality. PMID- 2930276 TI - Calcific shoulder periarthritis (tendinitis) in adult onset diabetes mellitus: a controlled study. AB - Two groups, one of 824 adult diabetics and one of 320 age and sex matched non diabetics, were examined for abnormal glucose metabolism and calcifications on anteroposterior shoulder x rays. Two hundred and sixty two (31.8%) of the diabetics had shoulder calcification compared with 33 (10.3%) of the control group, with a preponderant localisation in the right shoulder. Diabetes of long duration treated with insulin for a long time was associated with a larger percentage of shoulder calcifications. These data and previous laboratory findings suggest a possible pathogenetic correlation between the prevalence of calcific shoulder tendinitis and diabetes. PMID- 2930278 TI - Peripheral arthritis in the elderly: a hospital study. AB - One hundred consecutive patients admitted to an acute geriatric unit were examined for evidence of peripheral arthritis with recognised criteria used to define osteoarthritis, rheumatoid arthritis, pyrophosphate arthropathy, gout, and disorders of the shoulder joint. The presence of arthritis and its severity were related both to functional independence and to a recognition by the patient that joint problems were impairing independence. Seventy six patients had clinical peripheral arthritis; 48 had arthritis contributing to loss of function, and 19 of these did not volunteer evidence of their joint disease. The common occurrence of arthritic conditions in the elderly, with consequential disability and dependency, suggests that increased medical awareness may be required to prevent unnecessary morbidity. Our findings need confirmation in community based studies. PMID- 2930277 TI - Presence of glycosaminoglycans in purified AA type amyloid fibrils associated with juvenile rheumatoid arthritis. AB - Previous studies have strongly suggested an association between glycosaminoglycans and tissue deposits of amyloid. The present study was aimed at studying this association in purified preparations of hepatic amyloid fibrils obtained from human AA type secondary amyloidosis. Glycosaminoglycans were isolated by gradient ion exchange chromatography of purified amyloid fibrils treated with pronase. Degradation with specific enzymes identified the glycosaminoglycans as chondroitin sulphate, dermatan sulphate, and heparin/heparan sulphate. The total amount of glycosaminoglycans specifically coisolated with the amyloid fibrils was 15 micrograms/mg fibril weight. The presence of glycosaminoglycans in amyloid may play a part in the incorporation of structurally diverse protein precursors into amyloid fibrils of identical ultrastructure. PMID- 2930279 TI - An unusual case of systemic lupus erythematosus with isolated hypoglossal nerve palsy, fulminant acute pneumonitis, and pulmonary amyloidosis. AB - A 53 year old Chinese man with systemic lupus erythematosus (SLE) had an isolated 12th nerve palsy and acute pneumonitis. He died of respiratory failure despite intensive treatment. A limited necropsy was performed, and amyloid deposits were identified in both lung and kidney tissue. This case is highly unusual because (a) to our knowledge an isolated hypoglossal nerve palsy associated with active SLE has never been reported; (b) only one of nine reported cases of amyloidosis in patients with SLE had amyloid deposits in the lung. PMID- 2930280 TI - Pachydermoperiostosis (primary hypertrophic osteoarthropathy): report of a case with evidence of endothelial and connective tissue involvement. AB - A case of pachydermoperiostosis characterised by the presence of finger clubbing, periostosis, sweating of hands and feet is described. Modifications of capillaroscopic pattern and of arteriovenous anastomoses are reported. The periungual border and finger tip tissue showed diffuse endothelial hyperplasia, hyalinosis, and sclerosis with packing of collagen fibres. Electron microscopy showed hypertrophic and activated endothelia (numerous and hypertrophic Golgi complexes, several Weibel-Palade bodies, vesicles of micropinocytosis, and glycogen particles), the basal membrane thickened and reduplicated, perivasal infiltrate in superficial derma, reticulation and segmentary reduplication of basal membrane in arteriovenous shunt. In the perineural connective tissue numerous Luse bodies (long spacing collagen) were evident. The data indicate that in the early phase of pachydermoperiostosis morphological endothelial and collagen fibre abnormalities are present, though there is a normal peripheral blood flow. PMID- 2930281 TI - Acute non-infectious arthritis of the hip in rheumatoid arthritis: synovial membrane findings. AB - A case of acute hip pain in rheumatoid arthritis is presented, with synovial membrane findings. A patient with classical rheumatoid arthritis suffered three unusual bouts of sudden, severe but transient hip pain. The hips were clinically normal between these episodes. The clinical picture on two of these occasions strongly suggested septic arthritis. Although the synovial fluid was highly inflammatory, cultures were negative. The synovial membrane showed mild lining cell hyperplasia, vascular congestion, and scattered inflammatory cells, predominantly lymphocytes. These findings were not compatible with either pyogenic infection or longstanding rheumatoid arthritis. The clinical and pathological features of acute non-infectious arthritis of the hip appear to delineate a distinct syndrome. PMID- 2930282 TI - Chronic Q fever with mixed cryoglobulinaemia. AB - A 47 year old woman presented with a six month history of vasculitic rash, splenomegaly, and cardiac murmurs. Investigations showed the presence of mixed cryoglobulinaemia and raised titres to Coxiella burnetii consistent with chronic Q fever infection. The patient was treated with tetracycline (1 g four times a day). PMID- 2930283 TI - Anaemia in rheumatoid arthritis. PMID- 2930284 TI - Absence of an association between ankylosing spondylitis and IgA nephropathy. PMID- 2930285 TI - Microgastrinomas of the duodenum. A cause of failed operations for the Zollinger Ellison syndrome. AB - Gastrinomas are now being detected at an earlier stage than was formerly the case. Furthermore, with the ability to control acid secretion, emphasis has been placed on identifying gastrinoma patients who are potentially curable by tumor resection rather than by palliative gastrectomy. Despites estimates suggesting that 20-40% of sporadic gastrinoma patients can be successfully resected for cure, as many as 40% of such patients have occult tumors that elude detection. In an effort to better localize gastrinomas, we have used percutaneous transhepatic venous (THVS) gastrin sampling over the past 10 years. From 1978 to 1988, THVS was used in 46 patients in whom there was no other evidence of metastatic gastrinoma by conventional studies. Gastrinomas were found at operation in all but one patient. The purpose of this report is to emphasize that occult tumors are most often found in the duodenal wall, and frequently they may be no greater than 2 mm in diameter. Five recent cases illustrate that these small tumors or microgastrinomas may be the sole source of hypergastrinemia and can be cured by local excision. These recent cases emphasize that microgastrinomas are not usually palpable through the duodenal wall. They may be detected only after duodenotomy and meticulous evaluation of the mucosa by eversion and direct palpation. Duodenotomy and intraluminal exploration should be considered an essential component of the operation for patients with extrapancreatic gastrinomas. PMID- 2930286 TI - Effects of sham feeding and a meal on plasma gastrin and duodenal pH in normal and duodenal ulcer patients. AB - The roles of plasma gastrin and duodenal acidity in duodenal ulcer disease remain unclear. In this pathophysiologic study, plasma gastrin and dual gastro-duodenal pH were measured before, during, and after cephalic stimulation (modified sham feeding) and the ingestion of a meal in 16 duodenal ulcer (DU) patients and twelve healthy subjects. Gastrin levels were significantly higher in DU patients both in the fasting state (42.5 ng/l vs. 22.5 ng/l, p less than 0.001) and after the meal (130 vs. 60, p less than 0.02). Two separate patient subsets were identified: a "hypergastrinemic" (HRG) group exhibiting exaggerated gastrin responses and a "Normogastrinemic" (NOG) group comprised of patients with gastrin levels similar to those of controls. Only the HRG group exhibited a significant gastrin response to sham feeding. Both patient groups exhibited a delayed onset of duodenal acidity and delayed peak acid response after feeding indicative of delayed gastric emptying of the acid load. The HRG group exhibited a longer duodenal acid exposure and a prolonged return to premeal pH levels, suggesting a defective switch-off mechanism of acid secretion after duodenal acidification. PMID- 2930287 TI - A multifactorial analysis of factors related to lethality after treatment of perforated gastroduodenal ulcer. 1935-1985. AB - One thousand one hundred and twenty-eight patients treated for perforated gastroduodenal ulcer during the years 1935-1985 were studied at the Haukeland University Hospital. The majority of patients (97.7%) were treated surgically. The data was analyzed by contingency tables and chi square testing, and a stepwise logistic regression analysis was performed in order to reveal interactions between variables and to elucidate time trends in lethality rates. The total postperforation lethality was 7.4%, the postsurgical death rate was 6.6%, and the death rate among conservatively treated patients was 42.3%. Lethality was significantly influenced by year of hospital admission and increased markedly with the age of the patients. For all age groups, the lethality decreased markedly with time. Treatment delay was associated with a moderate but significant increase in lethality. In patients with gastric ulcer the lethality was 3.6 times higher than in those with duodenal ulcer. The death rate was similar in the duodenal and pyloric ulcer groups. Death rate decreased with time in both stomach ulcer, duodenal, and pyloric ulcer patients. There was no sex difference and no difference between patients treated with simple suture or gastric resection. PMID- 2930288 TI - Hepatic resection of metastasis from colorectal carcinoma. Morbidity, mortality, and pattern of recurrence. AB - To identify the factors that determine the morbidity and mortality of liver resection of metastases from colorectal carcinoma and the variables that may influence the pattern of recurrence, the survival time and the disease-free rate, a univariate and-multivariate statistical analysis (30 variables using Student's t-test, Fischer's exact test, and chi square test) was performed. Intraoperative blood loss of greater than 3500 ml was found to be a significant risk factor to developing postoperative complications (p less than 0.05 by x2). After a mean follow-up of 25.8 months, 26 of the 35 patients studied (74%) had recurrent disease. In the univariate analysis, the following factors appear to be reliable predictors of early recurrence: poor degree of differentiation of the primary colorectal tumor, the presence of multiple liver metastases, the male gender, and the presence of tumor at the margin of the resected hepatic tissue (p less than 0.05). However, only the latter two factors appeared also to affect the survival time and the disease-free rates at 2 years after hepatic resection of metastases (p less than 0.05). In the multivariate analysis (factors tested simultaneously), presence of an advanced liver metastatic disease (Stage II or III) consistently indicated early recurrence and poor survival (p less than 0.005). The liver was the most common site of recurrence as the sole site of recurrence (54%) or in combination with other sites (88%)--followed by the lungs (31%) and the site of colonic resection (8%). Twenty-nine (83%), 14 (40%), and nine (26%) patients survived without recurrent disease at 1, 2, and 3 or more years, respectively, after hepatic resection of metastases. In six patients (17%), no significant palliation was noted, primarily because of early recurrence (less than 6 months). From this data, resection of hepatic metastases from colorectal cancer appears to offer a realistic therapeutic option to a selected group of patients, but only if the resective procedure can be performed with an operative mortality rate of less than 5%. PMID- 2930289 TI - Acute cholangitis. Multivariate analysis of risk factors. AB - In order to identify risk factors in patients with acute cholangitis, 140 clinical, biochemical, etiologic, and pathologic variables of 449 attacks of acute cholangitis seen in one center over a 20-year period were analyzed. Simple regression revealed 24 factors with prognostic significance, but multivariate analysis detected only seven factors with independent significance in predicting mortality (acute renal failure, cholangitis associated with liver abscesses or liver cirrhosis, cholangitis secondary to high malignant biliary strictures or after percutaneous transhepatic cholangiography, female gender, and age). When the presence of each of these factors is weighted proportional to its coefficient of regression, patients with cholangitis could be scored on a scale of 0-27. A score of seven was clinically the most useful cut off--388 attacks of cholangitis associated with a score of less than 7 had a mortality rate of only 1.8%, whereas 61 attacks associated with a score greater than or equal to 7 had a mortality rate of 49%. The value of this scoring system needs to be confirmed in prospective studies, but it may prove useful, for example, in selecting a group of high-risk patients for urgent biliary decompression in an attempt to reduce the mortality associated with this pathology. PMID- 2930290 TI - The influence of injury severity on complication rates after primary closure or colostomy for penetrating colon trauma. AB - The management of penetrating colon injury has been frequently debated in the literature, yet few reports have evaluated primary closure versus diverting colostomy in similarly injured patients. Diverting colostomy is the standard of care when mucosal penetration is present, but primary closure in civilian practice has generally had excellent results, although it has been restricted to less severely injured patients. Because the degree of injury may influence choice of treatment in modern practice, various indices of injury severity have been proposed for assessment of patients with penetrating colon trauma. As yet, however, there has been no cross-comparison of repair type versus injury severity. A retrospective study 76 patients who sustained penetrating colon trauma between January 1, 1979 and December 31, 1985 and who survived for at least 24 hours was conducted. Different preferences among attending surgeons and a more aggressive approach to the use of primary closure during the years of study led to an essentially random use of primary closure and diverting colostomy for moderate levels of colon injury, with mandatory colostomy reserved for the most serious injuries. Primary closure was performed in 37 patients (three having resection and anastomosis), and colostomy was performed in 39 patients. Severity of injury was evaluated by the Injury Severity Score (ISS), Penetrating Abdominal Trauma Index (PATI), and the Flint Colon Injury Score. Complications and outcome were evaluated as a function of severity of injury, and primary closure and colostomy were compared. Demographic profiles of the two groups did not differ regarding age, sex, mechanism of injury, shock, or delay between injury and operation. The mortality rate was 2.6% for each group. Major morbidity, including septic complications, occurred in 11% of the patients of the primary closure group and in 49% of those of the colostomy group. When PATI was less than 25, the Flint score was less than or equal to 2, or when the ISS was less than 25, primary closure resulted in fewer complications than did colostomy. Of the injury severity indices examined, the PATI most reliably predicted complications and specifically identified patients who whose outcome would be good with primary repair. These results suggest that the use of primary closure should be expanded in civilian penetrating colon trauma and that, even with moderate degrees of colon injury, primary closure provides an outcome equivalent to that provided by colostomy. In addition, the predictive value of the PATI suggests that it should be included along with other injury severity indices in trauma data bases. PMID- 2930291 TI - Tracheostomies in burn patients. AB - The use of tracheostomies in burned patients with inhalation injuries is now reserved for specific indications rather than as prophylactic airway management. A 5-year burn center experience with tracheostomies used in this fashion is presented. Ninety-nine tracheostomies were performed in 3246 patients who had indications of prolonged respiratory failure or acute loss of airway. Although colonization of the sputum was universal, neither rates of pulmonary sepsis nor mortality were significantly increased in patients who underwent tracheostomies. Twenty-eight patients developed late upper airway sequelae, including tracheal stenosis (TS), tracheoesophageal fistula (TEF), and tracheoarterial fistula (TAF). Duration of intubation correlated only with development of TAF, whereas patients in whom TEF developed were significantly older and more likely to have evidence of tracheal necrosis at the time of tracheostomy. The pathogenesis of upper airway sequelae in these patients as divergent responses to the combined insults of inhalation injury, infection, and intubation is considered. PMID- 2930292 TI - Central venous catheter vascular erosions. Diagnosis and clinical course. AB - Central venous catheter (CVC) vascular erosions are difficult to diagnose, and they cause serious complications. From 1985 to 1987, ten patients receiving the surgical services at the University of Florida suffered CVC vascular erosions. By chest roentgenogram, nine CVC tips were in the superior vena cava (SVC), although three catheter tips abutted the lateral wall of the SVC. One catheter tip was in the right atrium. All patients had sudden onset of symptoms, the most common of which was shortness of breath. Initial diagnosis was respiratory insufficiency in five patients, cardiac failure in three patients, pulmonary embolism in one, and sepsis in one. Four patients required intensive care. Two patients suffered pericardial tamponade, and pleural effusions developed in eight patients. One patient died of cardiac arrest. The average time interval from CVC placement to onset of symptoms was 60.2 hours, and from the onset of symptoms to the time of diagnosis, the interval was 16.7 hours. The mean volume obtained at thoracentesis was 1324 ml and at pericardiocentesis was 250 ml. PMID- 2930293 TI - Primary blast injury after a bomb explosion in a civilian bus. AB - A 6-kg explosive charge detonated under a seat in the center of a crowded city bus in Jerusalem, killing three passengers immediately. Of the 55 survivors, all of whom were transferred to two major medical centers, 29 were hospitalized. Among those admitted, a high rate of primary blast injuries was found, including perforated ear drums (76%), blast lung (38%), and abdominal blast injuries (14%). Two of the latter patients suffered bowel perforations, which were diagnosed with considerable delay. Eight patients (31%) had sustained life-threatening trauma, consisting of a combination of primary, secondary, and tertiary blast injuries. The overall mortality rate was 10.3%. The large number of primary blast injuries, including the unexpected finding of bowel perforations, is explained by the high amplitude of the air pressure wave (3.8-5.2 atm) and its relatively long duration (2-3 msec) resulting from the detonation of the high-energy explosive charge in the small, enclosed space of the bus. Besides the usual wounds sustained by victims of an explosion that occurs in a confined space, the possibility of primary blast injury to the abdomen and to the lungs should be taken into account by the treating surgeon. PMID- 2930294 TI - Long-term follow-up of patients with biopsy-proven benign breast disease. PMID- 2930295 TI - Role of feces, necrotic tissue, and various blocking agents in the prevention of adhesions. PMID- 2930296 TI - Reoperation for congenital choledochal cyst. PMID- 2930297 TI - Choosing cardiothoracic surgical residents. PMID- 2930298 TI - Esophagectomy for achalasia: who, when, and how much? PMID- 2930299 TI - Does transfusion modify the outcome of cancer resections? PMID- 2930300 TI - Porcine versus pericardial bioprostheses: a comparison of late results in 1,593 patients. AB - From 1976 to 1988, 1,593 patients underwent valve replacement with a porcine (878 patients) or a pericardial bioprosthesis (715 patients). There were 701 aortic, 678 mitral, and 214 multiple-valve replacements. Follow-up was obtained for 1,559 patients (98%). Early mortality was 9% (79 patients) in the porcine valve group and 5% (37 patients) among patients with a pericardial valve (p less than 0.01). Late survival after replacement with porcine valves was 80% +/- 1% and 62% +/- 3% at 5 and 10 years, respectively. With pericardial valves, 5-year survival was 79% +/- 2%. Among valve-related complications, rates of freedom from thromboembolism, endocarditis, and hemorrhage after 6 years were similar for both valve groups. Freedom from reoperation at 6 years was also similar after aortic (96% versus 91%) or multiple-valve replacement (95% versus 88%). However, for mitral valve replacement, freedom from reoperation was significantly better with porcine valves than with pericardial valves at 6 years (92% versus 68%; p less than 0.001). This difference was mainly due to the Ionescu-Shiley valve, which accounted for 83% of primary tissue failures among pericardial bioprostheses implanted in the mitral position (10/12 patients). After 6 years, freedom from primary tissue failure of mitral valves was 92% +/- 2% with porcine and 70% +/- 11% with pericardial bioprostheses (p less than 0.0001). The degree of clinical improvement among survivors was similar with both valve types. Thus, in the aortic position, pericardial valves compare with porcine valves up to 6 years, whereas in the mitral position, the durability of the former is significantly less, mainly because of the suboptimal performance of the Ionescu-Shiley pericardial bioprosthesis. PMID- 2930301 TI - Esophageal function in patients with reflux-induced strictures and its relevance to surgical treatment. AB - Esophageal function was evaluated in 53 patients with increasing severity of esophageal injury caused by gastroesophageal reflux disease (study 1), and the findings were applied to the treatment of 28 patients with reflux-induced strictures (study 2). Fifty asymptomatic volunteers served as controls for both studies. In study 1 there were 14 patients without reflux complications, 14 with esophagitis grade I to III, 13 with esophageal stricture, and 12 with Barrett's epithelium (6 of whom had a stricture). The prevalence of a mechanically defective sphincter increased with the progression of the esophageal injury; 50% in the patients without complications to 84% and 92% in those with stricture or Barrett's epithelium, respectively. Similarly, a decrease in amplitude of contractions in the distal esophagus was observed in patients with stricture and patients with Barrett's epithelium. In study 2, these findings were applied in the surgical management of 28 consecutive patients with a reflux-induced stricture. Preoperative motility studies were performed after patients were dilated to 60F. Control of reflux by a Nissen fundoplication gave excellent (86%) to good (14%) results in patients who had relief of dysphagia after dilation or adequate motility, or both. Four patients with both persistent dysphagia after dilation and inadequate motility underwent resection. Transmural presented are helpful in the selection of the optimal surgical procedure for the treatment of dilatable reflux-induced strictures. PMID- 2930303 TI - Mucoepidermoid lung tumors. AB - Mucoepidermoid lung tumors are uncommon, representing 0.2% of all lung tumors and 1% to 5% of bronchial adenomas. Eighteen patients with mucoepidermoid tumors are reported. There were 10 male and 8 female patients with a mean age of 36.8 years (range, 9 to 62 years). On the basis of mitotic activity, cellular necrosis, and nuclear pleomorphism, we subclassified these tumors as low grade (15 patients) or high grade (3 patients). The achievement of complete resection and low-grade versus high-grade staging correlated with prognosis. All 12 patients who had a low-grade tumor that was completely excised are alive with no evidence of disease at a mean follow-up of 4.7 years (range, 1 to 27 years). All high-grade tumors proved fatal within 16 months. Two of the 3 high-grade tumors were unresectable because of extensive local disease. Patients with low-grade tumors and microscopically positive margins require close follow-up and can undergo a successful repeat resection. Nine of the 16 resections were sleeve resections, high-lighting the importance of conservative lung-sparing procedures in these central airway tumors. Both patients with an unresectable high-grade tumor had radiation therapy postoperatively and died 11 months later. The role of radiation therapy with high-grade tumors or incomplete resection has yet to be determined. PMID- 2930302 TI - Effect of sodium nitroprusside on spinal cord perfusion and paraplegia during aortic cross-clamping. AB - To evaluate the effects of sodium nitroprusside (SNP) on hemodynamics, cerebrospinal fluid dynamics, and neurological outcome after 30 minutes of thoracic aortic occlusion, we monitored proximal and distal blood pressure, cerebrospinal fluid pressure, spinal cord blood flow, and somatosensory evoked potentials. In group 1 (n = 6), no attempts were made to control proximal hypertension, whereas in group 2 (n = 6), proximal blood pressure was controlled with intravenous infusion of SNP. There was no significant difference in proximal or distal blood pressure or cerebrospinal fluid pressure between the two groups at baseline. During the crossclamp interval, the mean proximal aortic pressure rose from 108 +/- 21 to 146 +/- 14 mm Hg (p less than 0.001) in the control group, whereas the mean blood pressure in the SNP group was maintained at 99.8 +/ 12 mm Hg (p = not significant compared with baseline blood pressure). Mean distal aortic pressure decreased from systemic values to 23 +/- 7 mm Hg in control animals and to 11 +/- 5 mm Hg in the SNP group (p less than 0.005). In the latter group, cerebrospinal fluid pressure increased significantly from 10.6 +/- 1.9 to 20.1 +/- 5.5 mm Hg (p less than 0.005). In animals receiving SNP, spinal cord blood flow was decreased in the lower spinal cord segments and increased in the upper cord segments. When compared with controls, this difference did not reach significance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2930304 TI - Bronchial carcinoids: a review of 60 patients. AB - Sixty patients with a bronchial carcinoid underwent surgical treatment. Preoperative fiberoptic bronchoscopy revealed a characteristic pink, smooth, bleeding tumor in 71.4% of the patients with a typical carcinoid and 16.7% of those with an atypical carcinoid (p less than 0.05). Eight pneumonectomies, seven bilobectomies, 34 lobectomies, three lobectomies with bronchoplasty, six bronchotomies with bronchoplasty, and two segmental resections were performed. All patients entered follow-up, and 47 were followed for more than 5 years. Ten year survival was 89.6% for patients with a typical carcinoid and 60% for those with an atypical carcinoid. Ten-year survival was 88.1% for patients with carcinoids without lymph node involvement. All patients with lymph node involvement died within 5 years. Overall, 5 of the 8 patients having pneumonectomy died of acute cardiorespiratory failure. We conclude that a limited surgical resection with or without bronchoplasty and systematic lymphadenectomy is the procedure of choice in patients with typical carcinoids. On the other hand, atypical carcinoids are comparable to well-differentiated malignancies of the lung. Whenever possible, pneumonectomy should be avoided in favor of bronchial sleeve resection. PMID- 2930305 TI - Internal mammary artery grafts: the shortest route to the coronary arteries. AB - Inadequate length can limit the use of the internal mammary artery (IMA) for coronary revascularization. By following the shortest route from its origin to the recipient coronary artery, IMA use can be maximized. Seven cadavers were studied to determine that shortest route for the left and right IMAs. The shortest route for the left IMA to the left anterior descending coronary, diagonal, and circumflex coronary arteries was through the pericardium (p less than or equal to 0.01). For the right IMA, the significantly shortest routes were across the anterior heart for the left anterior descending and diagonal arteries, through the right pericardium for the right coronary artery or posterior descending artery, and through the pericardium and transverse sinus for the circumflex artery. Thus, any coronary artery can be reached with an in situ IMA, and the route through the pericardium is markedly shorter to ipsilateral coronary arteries. PMID- 2930306 TI - Incidence of residual defects determining the clinical outcome after correction of tetralogy of Fallot: postoperative late follow-up. AB - The postoperative results in 150 patients who had repair of tetralogy of Fallot (mean follow-up, 10.2 +/- 2.6 years) were defined as good in 71.3%, fair in 20.7%, and unsatisfactory in 8.0% on the basis of clinical criteria. Ninety-six percent of the patients are socially active, 92.0% have a good exercise tolerance, and 79.3% participate in sports. Data from 78 postoperative hemodynamic studies show mild right ventricular dysfunction in almost all patients examined. Peak systolic right ventricular/left ventricular pressure ratio decreased in the postoperative period in 65.4% of patients, remained unchanged in 3.8%, and increased in 30.8%. Minimal residual anomalies can modify the prognosis substantially. Of our patients, 53.3% of those with a shunt (p less than 0.05), 37.5% of those with stenosis (not significant), and 53.8% of those with pulmonary incompetences (p = not significant) have fair or unsatisfactory results. The associated defects are particularly unfavorable. Rhythm and conduction disturbances have resulted in fair or unsatisfactory results in 65.1% of patients. Such a disturbance occurring soon after bypass must be considered an incremental risk factor: 52.9% of patients seen with rhythm and conduction disturbances show the same disturbances later (p less than 0.001). PMID- 2930307 TI - Pacing lead fracture after a deceleration injury. AB - Acute pacemaker malfunction is potentially lethal. A high index of suspicion must be maintained in physicians caring for traumatized patients utilizing permanent pacing systems. We present a case of transvenous pacemaker lead fracture sustained in a vehicular deceleration injury. PMID- 2930308 TI - Left subclavian arterioesophageal fistula induced by a foreign body. AB - A left subclavian arterioesophageal fistula was diagnosed in a 35-year-old man at exploratory thoracotomy for suspected aortoesophageal fistula. After successful closure of the arterial fistula the patient developed a mediastinal abscess and esophagopleural fistula. The latter was successfully managed by retrosternal jejunal esophagoplasty followed by excision of the thoracic esophagus. This report documents a case of left subclavian arterioesophageal fistula and illustrates the importance of early diagnosis and surgical intervention of arterial perforation secondary to a foreign body in the esophagus. PMID- 2930309 TI - Familial multiple-organ arterial ectasia with massive hemoptysis. AB - Numerous large, thin-walled ectatic arteries up to 1 cm in diameter were encountered during operation on a 20-year-old patient. These vessels covered most of the right pleural surface. Similar symptomatic ectatic vessels were found arising from the left side and intracranially. Eight years later large arteriovenous malformations developed from chest wall and scar tissues that required ligations to control hemoptysis. This case was unique in that extensive multiorgan capillary and arterial systems were involved. PMID- 2930310 TI - Use of a new stapling instrument for permanent occlusion of the aorta in the surgical procedure for thromboexclusion. AB - Permanent aortic occlusion is required in the surgical procedures for the flow reversal and thromboexclusion technique and also for the permanent exclusion of aneurysms of the thoracic aorta. We have designed a stapling instrument for the permanent occlusion of the aorta and have used it in 5 patients with aortic dissections and 2 patients with aneurysms of the thoracic aorta. This report describes our newly designed surgical stapler for the closure of the aorta with 2 case reports. PMID- 2930311 TI - Angiocatheter coronary artery reperfusion before cardioplegia for evolving myocardial infarction. AB - A simple reperfusion method using an angiocatheter during total cardiopulmonary bypass before aortic cross-clamping is described. This method has been used successfully for catastrophic evolving myocardial infarctions. PMID- 2930312 TI - Is the shunt patent? AB - A novel technique for auscultating an aortopulmonary shunt murmur utilizing the principle of conduction of sounds through a closed air system is described. PMID- 2930313 TI - Extrinsic obstruction of the Medtronic-Hall disc valve in the mitral position. PMID- 2930314 TI - Mobilization technique in total esophagectomy. PMID- 2930315 TI - Budd-Chiari syndrome--pathogenesis and operative repair. PMID- 2930316 TI - Traumatic rupture of ascending aorta and left main bronchus. PMID- 2930317 TI - Treatment of impending sudden cardiac death. PMID- 2930318 TI - Complication of aortic dissection. PMID- 2930319 TI - Tunneling of defibrillator leads. PMID- 2930321 TI - The ontogeny of spontaneous skin potential responses in kittens. AB - The evolution of frequency and amplitude of spontaneous skin potential responses (SPRs) was studied in kittens from birth to 30 days. Results showed that: i) at birth, electrodermal activity is very low, and significantly lower than in adults; ii) the evolution of electrodermal activity is rapid, the adult level being reached by the end of the third week. Frequency and amplitude evolve at approximately the same rate; iii) SPRs recorded on the forepaw were significantly more frequent and larger than those for the hindpaw up to 13 days; iv) changes in electrodermal activity as a function of sleep and waking showed that sleep is characterized by a moderate decrease of SPR amplitude and by a pronounced decrease in SPR frequency. The results are discussed in terms of maturation of the central nervous system. PMID- 2930320 TI - Effects of intraoral mechanoreceptor stimulation on reticular formation neurones, in the rabbit. AB - The effects of intraoral mechanoreceptor stimulation on the firing rate of single neurones of the brain stem reticular formation (RF) were investigated in rabbits. 30% of RF neurones responded to periodontal mechanoreceptor stimulation; 16% to mucosal mechanoreceptor stimulation and 6% to both types of stimuli. Periodontal stimulation induced mainly inhibitory effects localized within the mesencephalic and rostral pontine RF. Among periodontal afferents incisors were the most widely represented. The effects of mucosal mechanoreceptor stimulation were predominant in the medullary and pontine RF and they were mainly excitatory. The present results support the hypothesis that brain stem RF neurones can be recruited into regulating mastication and biting also by stimulation of intraoral mechanoreceptors. PMID- 2930322 TI - The fine structure of the area postrema of the sheep. AB - The ultrastructural features of the area postrema (AP) were investigated in the suckling lamb, weaned lamb and adult sheep. No morphological differences were observed between lambs and sheep. Unciliated ependymal cells, linked by zonulae adherentes-type junctions and gap junctions, cover the AP ventricular surface. Clusters of pyriform neurons, glial cells, and axons are present in the parenchyma. The blood vessels are surrounded by wide perivascular spaces, which present an inner and outer basal lamina. The capillaries are of the fenestrated type. Perivascular glial cells rest on the outer basal lamina of the perivascular space and form a continuous ensheathment with their cell bodies or with flattened interdigitating processes. Along adjacent perivascular glial processes gap junctions are present. From our ultrastructural observations it appears that the overall cellular morphology of AP of the sheep does not differ substantially from that of monogastric mammals. PMID- 2930323 TI - [Introduction of a new method of study in legal medicine: high grade direct roentgen magnification with a 1 micron roentgen focus tube]. AB - The 1 mu focal spot x-ray tube, which had been developed for industrial purposes, allows for the first time high grade direct radiographic magnification. The first results with this new technique in forensic medicine are presented. Due to the high proportion of soft radiation, tiny glass fragments which can not be detected with conventional radiographic techniques, are visualized in the radiographic magnification. Furthermore, these foreign bodies can clearly be differentiated from other contrasted structures, like dust particles, subcutaneous fat etc. PMID- 2930324 TI - [Pattern of findings in injuries caused by "survival knives"]. AB - Survival knives are designed as multi-purpose tools. Most models have a broad single-edged fixed blade, like a trail-knife or Bowie-knife. The back of the blade normally has saw teeth set either in single line or double crossed line. This adds a third function, sawing, to the two standard functions of the knife (stabbing and cutting). The saw edge leaves characteristic scrape marks on the skin; bony structures are grooved or completely severed. A case of homicide is taken to demonstrate that the pattern of injuries may indicate the use of a survival knife. PMID- 2930325 TI - [Experimental studies of the development of linear electric current marks]. AB - By means of reconstructing electric current pathways electrophysical conditions were explored causing electrocution death in the bathtub, according to many authors quite often indicated by linear electric lesions. In our experimental settings we observed appearance of circumscribed linear marks of pallor similar to electric lesions in the region of postmortem lividity of corpses at the same level as bathtub water. None of typical histological indicators could be seen in skin samples. So no evidence was given for electric burns even under conditions of high density and extended duration of current. Similar linear marks and equivalent histological results were found when corpses were put into the bathtub filled with cold water without any experimental electric contact. CONCLUSIONS: Linear marks of pallor may occur at water level even without any electric contact to corpse or water neither bathtub. IMPLICATIONS: According to specific conditions mentioned above linear so called electric lesions at water level do not indicate electric current yet lethal electric damage. PMID- 2930326 TI - [Postmortem tissue embolisms. Report of 3 cases]. AB - In three cases of autopsy (cause of death - intoxication and drowning) we found in the lung intraalveolar und intravasal lymphatic tissue and bone-marrow. The results cannot be explained with violence during lifetime, but in tow cases as an effect of fracture of rips caused by external cardiacmassage, in one case by embalming with injection of conservation fluids. PMID- 2930327 TI - [Morphologic findings for airway occlusion in strangulation]. AB - Report of two cases of strangulation by hand. There were large submucous bleedings of the larynx (both sides of conus elasticus) of symmetrical arrangement, near the vocal processes of the arytenoid cartilages. They are believed to be the result of the violent contact of the vocal folds during laryngeal compression; perhaps while the arytenoid cartilages were subluxated inwards and downwards. Bleedings like this indicate the closure of the airway. In one case (50-year old woman) the ossified cricoid was broken; in the other (21 year old woman) the elastic laryngeal skeleton was intact, but large bleedings of the deeper tissues of both vocal folds indicated the vehement compression too. The analysis of 110 cases of attack against the neck (strangulation by hand -n = 30- or ligature -n = 30- alone or together -n = 32-; blunt force: n = 8, other types: n = 10) showed in 7 additional cases less typical but similar bleedings, especially in strangulation by hand. PMID- 2930328 TI - The effects of insurance generosity on the psychological distress and psychological well-being of a general population. AB - Reductions in the generosity of fee-for-service insurance lower the use of general medical and mental health services, but do they lead to lower mental health status for the covered population? We addressed this question using data from the RAND Corporation Health Insurance Experiment. Families in six sites in the United States were randomly assigned to one of 14 insurance plans for three- or five-year periods. On average, there were no significant adverse effects of cost-sharing plans, relative to a free-care plan, on either psychological well being or psychological distress, when the cost-sharing plans included full catastrophic coverage. Those with high mental health status but low income at baseline had significantly more favorable mental health outcomes on the cost sharing plans than on the free-care plan. We cannot definitively comment on the effects of insurance generosity for the sick poor. Our findings apply in the context of mandated comprehensive mental and general health coverage for a general nonelderly, nondisabled household population. PMID- 2930329 TI - Outpatient treatment of 'crack' cocaine smoking with flupenthixol decanoate. A preliminary report. AB - "Crack" cocaine abuse often produces severe cocaine dependence that is refractory to available pharmacological and outpatient psychotherapeutic treatments. We conducted two preliminary investigations evaluating the efficacy of flupenthixol decanoate, a depot xanthene requiring infrequent intramuscular administration, in the treatment of cocaine withdrawal. Ten outpatient crack cocaine smokers with poor prognoses were administered flupenthixol decanoate in an open-label, open ended trial. Flupenthixol decanoate was well tolerated and appeared to decrease cocaine craving and use markedly and rapidly, producing a 260% increase in the average time retained in treatment among these subjects. These promising but preliminary data, combined with the magnitude of problems presented by crack, warrant rapid, expanded double-blind assessment of flupenthixol decanoate in cocaine-abuse treatment. PMID- 2930331 TI - Dysphoric mania. Clinical and biological correlates. AB - Patients studied at peak severity of a manic episode showed substantial degrees of depression (dysphoria) and anxiety. Compared with nondysphoric manics (n = 26), the dysphoric manics (n = 22) had a significantly greater number of previous hospitalizations, and they displayed less rapid cycling both in the year before and during the index hospitalization admission. The severity of manic dysphoria tended to correlate with the number of previous hospitalizations, a finding that was highly significant in women (n = 27). Medication-free manic patients (n = 22) had significant elevations in cerebrospinal fluid norepinephrine concentrations compared with depressed and euthymic patients and normal volunteers, and the degree of elevation correlated significantly with the degree of manic dysphoria, anger, and anxiety rated at the time of the lumbar puncture. Patients with dysphoric mania, recognized by Kraepelin to have poor prognoses, have been reported to respond poorly to lithium carbonate but may be among those who respond to carbamazepine. Clinical, biologic, and pharmacologic response characteristics of manic subgroups, particularly those with extreme dysphoric components to their illness, appear to be clinically meaningful and deserving of further investigation. PMID- 2930330 TI - Obsessive-compulsive disorder in children and adolescents. Clinical phenomenology of 70 consecutive cases. AB - We reviewed the phenomenology of obsessive-compulsive disorder (OCD) in 70 consecutive children and adolescents studied prospectively at the National Institute of Mental Health, Bethesda, Md, between 1977 and 1987. There is striking similarity between the clinical presentation of OCD in children and in adult patients. Washing, grooming, and checking rituals and/or preoccupation with disease, danger, and doubt account for the great majority of cases. Twenty-five percent of subjects had a first-degree relative with OCD. The fixed content and style of symptoms within and across subjects, and the identical presentation across a wide age range, suggest an ethological model for OCD. PMID- 2930332 TI - Diagnostic criteria for melancholia. The comparative validity of DSM-III and DSM III-R. AB - The psychometric properties and validity of the DSM-III and DSM-III-R definitions of melancholia were examined in 60 depressed inpatients. The prevalence of melancholia was significantly higher according to the DSM-III-R criteria, and the kappa-coefficient of agreement between the two definitions was .40. For both criteria sets, the internal consistencies and item-scale correlations were low. Both definitions were associated with overall symptom severity and the melancholia symptom subscale; however, only DSM-III melancholics scored higher on the nonmelancholia symptom subscale. The DSM-III-R criteria were associated with more of the predicted correlates of endogenous subtyping. According to both definitions, melancholics were characterized by less stress, greater symptom severity, and less frequent nonserious suicide attempts prior to admission. The DSM-III-R melancholic subtyping was additionally associated with a family history of antisocial personality and substance abuse, presence of a premorbid personality disorder, age, and a tendency to blame others for the depression. PMID- 2930333 TI - Psychiatric diagnosis in an outpatient population. A comparative study of PSE Catego and DSM-III. AB - Two diagnostic systems are compared in a psychiatric outpatient population of 175 patients. The Present State Examination (PSE)-Catego system identified 121 patients (69%) as "cases," whereas DSM-III identified 152 patients (87%) as cases. The two systems converged in 115 patients, yielding a kappa coefficient of only .32. Approximately one third of the DSM-III cases that were not detected by the PSE-Catego system was due to the restricted coverage of the latter system; the remaining two thirds could be attributed to differences in threshold and time framing. Compared with DSM-III, the PSE-Catego system showed a strong bias toward depression, and the system was extremely insensitive to the detection of social phobias and obsessive-compulsive disorders. Only 58% of cases of depression and 46% of cases of anxiety were diagnosed by both systems. The results are compared with other studies, and some consequences are discussed. PMID- 2930334 TI - The development of DSM-IV. PMID- 2930335 TI - Effects of media violence on children. A review of the literature. AB - The effects of media violence on the behavior of children are controversial. We examined and reviewed studies addressing this issue and identified many mediating variables. A small but genuine association appears to exist between media violence and aggression. However, many unanswered questions persist, and no interventions are clearly indicated. PMID- 2930336 TI - DSM-III and DSM-III-R. PMID- 2930337 TI - Ciguatera poisoning presenting as psychiatric disorder. PMID- 2930338 TI - Blockade of the postictal prolactin surge by methysergide. PMID- 2930339 TI - Status report on interdisciplinary medical rehabilitation. PMID- 2930340 TI - Nutritional status during the acute stage of spinal cord injury. AB - This study was designed to help clinicians establish objective guidelines for meeting the nutritional requirements of spinal cord injury (SCI) patients during their initial hospitalizations. The nutritional status of 51 SCI patients treated between 1983 and 1986 was assessed at two, four, and eight weeks after injury. Nutrient deficiencies such as albumin (100% of patients), carotene (62%), transferrin (37%), ascorbate (25%), thiamine (24%), folate (20%), and copper (11%) were documented most frequently at two weeks postinjury. There was an average of 2.0, 1.6, and 1.2 nutrient abnormalities per patient at two, four, and eight weeks postinjury, respectively. Although most depressed nutrient parameters improved with time, diet-dependent plasma proteins such as albumin and transferrin remained low throughout the entire eight-week period. Mean body weight declined 1.3 +/- 3.9 kg during the first two weeks, 2.0 +/- 4.4 kg between two and four weeks, and 0.4 +/- 2.0 kg between four and eight weeks after injury. Significant findings also included a strong correlation between plasma albumin, ascorbate, and carotene levels and maximal inspiratory and expiratory pressure (p less than .05). Although nutrient status usually improved with time and was not definitely associated with an increased risk of secondary medical complications, prudence dictates that these deficiencies should be prevented by appropriate intervention. PMID- 2930341 TI - Electromyography of the pharyngeal musculature: technical considerations. AB - Thirty-one EMG studies of the pharyngeal musculature using three types of electrodes were performed. Electrode characteristics are compared according to criteria developed specifically for the pharynx; techniques for electrode positioning are described in detail; and technical difficulties encountered in performing these studies are discussed. Needle electrodes were best for analyzing individual potentials. For analyzing the timing of myoelectric activity, we preferred the hooked wire electrode (for palatopharyngeus or cricopharyngeus) or bipolar suction electrode (for pharyngeal constrictors). Pharyngeal electromyography is technically feasible and has a role in studying normal and pathologic processes. PMID- 2930342 TI - Upper extremity joint movement: comparison of two measurement devices. AB - The Ortho Ranger is a new device available for measurement of joint motion. The purposes of this study were (1) to determine the clinical reliability of the Ortho Ranger compared to the reliability of the standard goniometer and (2) to investigate the correlation between the Ortho Ranger and the goniometer for upper extremity joint movements in healthy adults. Three measurements with each instrument were taken during three different sessions for active shoulder, elbow, and wrist movements. The within-session reliability was higher for the goniometer. The Pearson correlation coefficients suggest a strong relationship between the Ortho Ranger and the goniometer for shoulder internal and external rotation, and a poor relationship for elbow movements. The Ortho Ranger does not provide remarkable advantages in measurement compared to the goniometer. PMID- 2930343 TI - Ankle and wrist weights: their effect on physiologic responses during treadmill running. AB - This study examined the effects of ankle and wrist weights on acute physiologic responses during treadmill running. Eight physically active young men completed eight running tests at their predetermined "most comfortable" speeds with zero, 1.6, 3.2, and 4.8 kg of additional weight equally distributed on the ankles or wrists. Energy expenditure and heart rate increased as a linear function of the additional weight placed at both anatomic locations. The magnitudes of these responses were significantly higher with the weights at the ankles than at the wrists, and were independent of the strength and endurance of the pertinent muscle groups involved in overcoming the additional weight. Blood lactate concentrations tended to increase during the loaded runs. However, the values were not significantly different from those observed during control (zero load) runs. Perceived exertion increased significantly over the control value when the heaviest weights were placed at the ankles and wrists. Since ankle and wrist weights increase training intensity and energy expenditure during treadmill running, they may result in greater increases in cardiovascular fitness and greater weight loss than would be realized by training without their use. PMID- 2930344 TI - First year after stroke: tracking cognitive and affective deficits. AB - A total of 58 cerebrovascular accident (CVA) rehabilitation inpatients with lateralized brain damage were assessed at two time points (T1 = admission to rehabilitation facility, about 7 weeks post-CVA, and T2 = 10 months post-CVA) in the following domains: hemispatial neglect, reaction time, depression, and affect comprehension. Performance was compared with 22 age-matched control subjects. Repeated measures ANOVAs were performed with patients subdivided into groups by laterality of lesion and visual field status (a strong predictor of psychometric performance, particularly in the hemispatial-neglect domain). During this initial year after stroke onset, significant improvements were observed in hemispatial neglect and affect comprehension in the two right-brain-damaged groups, but not the left-brain-damaged group. There was also a trend for improvement in observer rating of depression in all three groups. However, there was poor resolution of reaction time and self-reported depression in all three groups. These findings suggest that these latter domains should be targeted for more aggressive therapeutic intervention. An important component of such intervention, in addition to direct treatment of deficits, should be education of both patient and family as to the nature of deficits, expectations regarding resolution, and appropriate attributions of changed behavior after stroke. PMID- 2930345 TI - The Functional Assessment Screening Questionnaire: application for evaluating pain-related disability. AB - The Functional Assessment Screening Questionnaire (FASQ) is a 15-item checklist which was developed for primary care populations and may serve as a questionnaire method for evaluating disability which is associated with chronic pain. One hundred fifty-eight patients completed the FASQ as part of an initial multidisciplinary evaluation of chronic pain. Reliability was reaffirmed through split-half and alternate-form methods. Responses were examined to explore relationships to aspects of disability. Although job functions were not directly assessed, the scores of employed vs unemployed respondents differed significantly. Findings were related to Minnesota Multiphasic Personality Inventory scale scores but appeared to reflect a separate phenomenon. Scale 1 (Hs) was the most useful scale for predicting level of reported impairment. Nonparametric methods showed levels of functioning varying significantly by site of pain complaint. Patients with back pain reported the most difficulty; those with head pain and genital pain reported the least difficulty. An internal structure appropriate to chronic pain populations was discerned, with two general factors measuring either physical-motoric or cognitive-social aspects of disability. Aside from constraints associated with the use of self-report methods, the FASQ may be helpful as part of efforts to portray pain-related disability. PMID- 2930347 TI - Brain injury: functional outcome in children with tracheostomies and gastrostomies. AB - Survival, functional outcome, placement, and need for appliances at six and 24 months after either anoxic metabolic encephalopathies (AME) or traumatic head injuries (TI) were determined in 36 children with both tracheostomies and gastrostomies who were discharged from acute care hospitals. Five deaths occurred in totally dependent children with both tracheostomies and gastrostomies in place. Ten of 22 children with TI (48% of survivors) achieved independence in three functional areas by two years, whereas none of 14 with AME achieved functional independence in any area at two years (p = 0.001). Only one of the 18 who were dependent in all three areas at six months achieved partial independence in any area on reevaluation at two years. Institutionalization at two years was strongly predicted by six-month functional status (p less than 0.01). Four of 18 children dependent at six months returned to home care by two years, whereas all 16 children who achieved partial independence within six months of insult were cared for at home at two years (p less than 0.001), regardless of age or injury type. The need for tracheostomy at two years correlated with functional status at six months (p less than 0.01). Two-year survival was unexpectedly high for this group of children when compared to studies in adults. Functional status at six months is a strong predictor of dependency and institutionalization at two years. PMID- 2930346 TI - Perceived articulatory adequacy and velopharyngeal function in dysarthric speakers. AB - Twenty-four dysarthric speakers with etiologies of brain injury or stroke were placed into one of two groups based on aerodynamic measures of velopharyngeal status. Group I contained 13 individuals who were velopharyngeally incompetent in that nasal air flow was always noted during the stop phase of voiceless plosive sounds. Group II contained 11 individuals who at times achieved complete velopharyngeal closure. Certain measures of perceived articulatory adequacy were found to distinguish between the two groups. Specifically, speakers who were velopharyngeally incompetent produced an articulatory error pattern characterized by better performance for the consonant subcategory nasals-glides than for pressure consonants. Speakers who at times were achieving velopharyngeal closure did not exhibit a marked difference between these two consonant subcategories. Clinical use of measurement of articulatory adequacy as a gross indicator of velopharyngeal competence is suggested and limitations are discussed. PMID- 2930348 TI - Quantitative assessment of head and shoulder posture. AB - Posture of the head, neck, and shoulders has long been recognized as a factor contributing to the onset and perpetuation of cervical pain dysfunction syndromes. Treatment regimens frequently include exercises and instruction for postural correction. Clinical assessment of posture, however, tends to be subjective in nature. The purpose of this study was to determine the reliability of a new objective technique of posture measurement and to establish normal standards for the technique. This study used a computer-assisted slide digitizing system called Postural Analysis Digitizing System (PADS) to determine characteristic values for head and shoulder girdle posture and characteristic range of motion for head protraction-retraction and shoulder protraction retraction in a sample of able-bodied young men. PADS is a modification of a two dimensional slide digitizing system developed for measuring trunk range of motion. Twenty male subjects were photographed in a neutral position, the maximally protracted position, and the maximally retracted position of the head and scapula. Ten subjects were evaluated once, and ten were evaluated twice. The slide photographs were analyzed using a computer-assisted digitizing system. Well defined anatomic landmarks were used to determine angular relationships in the head, neck, and shoulders. The reliability of the system was tested by calculating an intraclass correlation coefficient, student t-test, and the percent error for each position. The positions were considered reproducible, and reliability of the system was considered adequate for postural analysis. Mean values for the positions were 28.48 degrees, 51.97 degrees, and 62.09 degrees for head protraction, the neutral position, and head retraction, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2930349 TI - Common bile duct healing. Do different absorbable sutures affect stricture formation and tensile strength? AB - Few basic investigations have addressed the problem of common bile duct strictures. We systematically investigated the healing canine end-to-end choledochal anastomosis and tested the hypothesis that common bile duct anastomoses sutured with monofilament polyglyconate absorbable suture would heal with less stricture formation and greater tensile strength than those sutured with braided polyglactin 910 and chromic catgut sutures. Seventy-six canines, randomized to control vs sutured groups, underwent either mobilization (controls) or transection of the mid-common bile duct and were allowed to heal 5, 10, 15, or 50 days postoperatively before sacrifice. The type of absorbable suture used to construct a common bile duct anastomosis was found to have no major effect on anastomotic strictures nor on anastomotic breaking strength. Polyglyconate suture caused significantly less perianastomotic inflammation than did chromic suture, with polyglactin 910 sutures evoking an intermediate inflammatory response. Surgeons may safely choose sutures for biliary procedures based on the clinical circumstances and personal preference. PMID- 2930350 TI - Epidural anesthesia in patients undergoing thoracic surgery. AB - Epidural anesthesia has been reported to exert beneficial effects in surgical procedures. Over the past 3 years at the Veterans Administration Medical Center in Washington, DC, thoracic surgical procedures have been done using a combined technique of epidural anesthesia with light general anesthesia. A retrospective review of this experience from January 1984 to November 1987 was done in 90 consecutive patients. Postoperative extubation of patients was accomplished immediately in 32%, within 1 hour in 34%, within 3 hours in 28%, within 18 hours in 4%, and was prolonged in only 1% of patients. Mortality was 2% and morbidity was 3%. This analysis indicates that the technique of epidural anesthesia with light general anesthesia provided satisfactory anesthesia with low mortality and morbidity in a high-risk group of patients undergoing surgery. PMID- 2930351 TI - Pelvic fracture hemorrhage. Priorities in management. AB - Hemorrhage remains the leading cause of mortality in patients with severe pelvic fractures. To evaluate diagnostic and treatment priorities for this problem, we retrospectively reviewed 245 consecutive patients admitted to our institution with pelvic fractures. Supraumbilical diagnostic peritoneal lavage (DPL) was grossly positive in 27 patients, and eight (30%) of these had life-threatening intra-abdominal hemorrhage identified at laparotomy. No patient with a positive DPL by count alone had life-threatening intra-abdominal hemorrhage. Pelvic fracture stabilization with early external pelvic fixation was associated with less requirement for blood transfusion (10 +/- 1 U) than with the pneumatic antishock garment (17 +/- 3 U). Nine patients with pelvic arterial injuries underwent angiographic embolization, and eight patients died (89%). We conclude that pelvic angiography should be performed before laparotomy in hemodynamically unstable patients with pelvic fracture, unless the DPL is grossly positive. PMID- 2930352 TI - Hemodynamic effects on endothelial cell monolayer detachment from vascular prostheses. AB - The establishment of an early blood-contacting endothelialized surface may improve the graft-host relationship. This study evaluated the adherence of indium 111-radiolabeled endothelial cells that were cultured to confluence on fibronectin-treated polyester elastomer (Hytrel) grafts that were perfused for two hours on a pulse duplicator apparatus under high- and low-shear conditions. Perfusate samples were serially assayed for radioactivity. After perfusion, grafts were sectioned into four segments and assayed for retained radioactivity. All graft segments were hematoxylin stained and examined under light microscopy for evaluation of cell density. Excellent endothelial cell adherence (90%) was observed under both hemodynamic conditions at 120 minutes, with most losses occurring within the first 15 minutes. No differences were seen between high- and low-shear conditions or proximal vs distal graft segments. PMID- 2930353 TI - Recombinant human tumor necrosis factor produces hemodynamic changes characteristic of sepsis and endotoxemia. AB - Tumor necrosis factor (TNF) is a macrophage-derived peptide mediator released during endotoxemia and sepsis. We examined the systemic and visceral hemodynamic response to low doses of human recombinant TNF in rats. Each animal received a 30 minute intravenous infusion of either saline solution (n = 8) or TNF (n = 8) in a dose of 0.25 mg/kg or 1.0 mg/kg. Thermodilution cardiac output, blood pressure, pulse, vascular resistance, effective hepatic blood flow (galactose clearance), and effective renal plasma flow (p-aminohippurate clearance) were determined at time = 2 hours. The 0.25-mg/kg dose had no apparent effect on systemic hemodynamics. The 1.0-mg/kg dose produced a hyperdynamic systemic circulatory response with an elevated cardiac output, tachycardia, and a diminished systemic vascular resistance. Effective hepatic blood flow was exquisitely sensitive to even the lowest dose of TNF, with a 29% reduction despite the normal cardiac output. Renal flow was unaffected by either dose. Tumor necrosis factor-induced systemic and visceral hemodynamic changes are remarkably similar to those seen in gram-negative sepsis, suggesting that TNF may occupy a proximal position in the pathogenesis of overwhelming infection. PMID- 2930354 TI - Effective hepatic blood flow during cardiopulmonary bypass. AB - Hepatic dysfunction following cardiopulmonary bypass (CPB) is a relatively frequent finding, and jaundice occurring after CPB is associated with an increased mortality rate. Post-CPB jaundice may be a consequence of inadequate liver perfusion during CPB. To evaluate the potential impact of CPB on effective hepatic blood flow, 10 patients undergoing CPB for cardiac procedures were studied. Effective hepatic blood flow was measured in each patient during the operative procedure but before institution of CPB and during CPB as well. Effective hepatic blood flow was measured by the galactose clearance technique. Blood lactate and pyruvate levels were also measured before and during CPB. During CPB, effective hepatic blood flow was consistently reduced by an average of 19%. Although for most patients this reduction seems well tolerated, in a minority of patients it may contribute to postoperative hepatic dysfunction. PMID- 2930355 TI - Concomitant cholecystectomy for asymptomatic cholelithiasis. AB - The outcome of 68 patients with asymptomatic cholelithiasis undergoing laparotomy for other conditions was reviewed to determine those most likely to become symptomatic postoperatively. Thirty-seven patients (54%) became symptomatic postoperatively. Eight patients (22%) required cholecystectomy within 30 days of operation or within the same hospitalization. These patients fasted for a longer period of time postoperatively (15 +/- 21 vs 4 +/- 3 days) than those undergoing later cholecystectomy. Significantly more of these patients required transfusion (38% vs 7%), mechanical ventilation (50% vs 11%), and total parenteral nutrition (50% vs 18%). Cholelithiasis frequently becomes symptomatic after laparotomy for other intra-abdominal conditions. Patients who require mechanical ventilation, transfusions, and parenteral nutrition and who are slow to resume enteral nutrition are more likely to require early cholecystectomy. Concomitant cholecystectomy adds minimal morbidity to other procedures and should be undertaken unless specific contraindications exist, particularly in this high risk group. PMID- 2930356 TI - Reversal of pigment gallstone disease in a canine model. AB - Unlike dietary-induced cholesterol gallstones, which may disappear spontaneously when the lithogenic diet is withdrawn, little is known about the natural history of pigment gallstones. We examined whether pigment gallstone disease, which can be uniformly induced in the dog by six weeks of a methionine-deficient diet, can be reversed by return to normal diet. As previously reported, all dogs develop pigment gallstones as well as significant increases in biliary total calcium, free ionized calcium, and cholesterol concentrations after six weeks of a lithogenic diet. These changes are accompanied by a significant increase in the concentration of unconjugated bile salts in bile. In addition, histologic changes in the gallbladder wall occur that are consistent with a moderate degree of chronic cholecystitis. This study clearly demonstrates that return to a normal diet for six weeks allows bile composition to normalize, gallstones to disappear in 50% of dogs, and gallbladder histologic changes to return toward normal. Thus, it would appear that pigment gallstone disease in this model may be reversible, at least early during its course. Although the relevance of these findings to pigment gallstones in humans must be established, the potential for nonoperative treatment of pigment gallstones should not be discounted. PMID- 2930357 TI - Detection of the cancer-prone colon, using transepithelial impedance analysis. AB - Alterations in ionic conductance may represent an early mitogenic signal; therefore, impedance analysis was used to examine differences in the electrical properties of the distal colon in a cancer-susceptible (CF1) and a cancer resistant (DBA) strain of mouse following administration of the carcinogen dimethylhydrazine. The electrical conductance of the surface colonic epithelium increased in CF1 mice from a mean (+/- SEM) of 41.1 +/- 3.0 milliSiemens.cm-2 (mS.cm-2) in controls to 52.6 +/- 3.1 mS.cm-2 following dimethylhydrazine treatment. The conductance decreased in the cancer-resistant DBA group from 154.6 +/- 44.1 mS.cm-2 in controls to 35.1 +/- 17.2 mS.cm-2 following dimethylhydrazine treatment. This difference in response to the carcinogen may partly explain differences in susceptibility noted between these two species. Epithelial impedance analysis may be of use in the early detection of the colon at risk for subsequent cancer development. PMID- 2930358 TI - Limitations to donating adequate autologous blood prior to elective orthopedic surgery. AB - We reviewed 175 patients who predeposited autologous blood prior to elective orthopedic surgery to define potential limitations of procuring adequate autologous blood. These potential limitations include physician underordering, storage interval, and erythropoietic response. We found that a continuing medical education intervention increased the amount of autologous blood requested by physicians for storage: from 121 U for 50 patients (mean = 2.4) before CME to 195 U for 65 patients (mean = 3.0) afterward; eight (16%) of 50 patients had 4 U or more requested before CME vs 25 (38%) of 65 patients afterward. Continuing medical education had no impact on mean (+/- SD) effective storage interval, 22.6 +/- 9.0 vs 21.6 +/- 9.4 days. Thirty (17%) of 175 patients were deferred (hematocrit less than or equal to 0.34) and were unable to donate units of blood requested; of these, 13 (43%) received homologous blood compared with 19 (13%) of 145 not deferred. We conclude that a significant percentage of patients are deferred from autologous donation because of hematocrit limitations and receive homologous blood. This problem is not related to physician underordering or inappropriate physician transfusion behavior, but rather to the erythropoietic response to serial phlebotomy over a limited storage interval. Future studies should focus on mechanisms to maximize autologous blood procurement. PMID- 2930359 TI - Cardiac contusion. The effect on operative management of the patient with trauma injuries. AB - Sixty-four patients with cardiac contusion documented by electrocardiographic changes and creatine kinase MB fraction assay following blunt chest injury were reviewed to assess the impact of cardiac contusion on subsequent management. Fifty-eight patients had elevated creatine kinase MB levels; 35 patients had electrocardiographic abnormalities, including ST-segment and T-wave changes (25), premature ventricular contraction (ten), right bundle-branch block (nine), atrioventricular block (three), atrial fibrillation (three), and premature atrial contraction (two). Thirty patients underwent general anesthesia. There were only four perioperative complications: ventricular ectopy, ventricular fibrillation, nodal rhythm, and pulmonary edema. There were no deaths attributable to cardiac contusion. In summary, patients with blunt trauma who have sustained a cardiac contusion can undergo elective operation with a low incidence of complication. In the emergency setting, however, hemodynamic monitoring for early detection of arrhythmias is indicated. PMID- 2930360 TI - Endorectal ileal pullthrough. PMID- 2930361 TI - Hepatic packing in major hepatic trauma. PMID- 2930362 TI - Intestinal malrotation and midgut volvulus with intussusception: an unusual association. PMID- 2930363 TI - Nurses--1: osteoporosis--0. PMID- 2930364 TI - Clinical applicability of insert earphones for audiometry. AB - Insert transducers for audiometry are available which may offer significant advantages over older 'standard' headphones. Clinicians have remained cautious in using such devices due to the paucity of experimental data demonstrating their comparability with more widely used devices. The purpose of this investigation was to compare and contrast pure-tone audiometric thresholds obtained using insert earphones with those measured utilizing conventional supra-aural transducers in normal and hearing-impaired subjects. A second purpose was to examine the differential effects on the hearing threshold level of two coupling systems for the insert device. There were no clinically significant differences among pure-tone thresholds measured with the three earphone/coupler arrangements for subjects with normal and impaired hearing. Advantages and limitations of insert earphones are discussed. PMID- 2930365 TI - [Development of a French-Quebec lipreading test]. AB - To date, there has been no validated speech-reading test available for the French Canadian population. In the context of rehabilitative services for persons with noise-induced hearing loss, it was felt necessary to develop and validate a speech-reading screening test. Thirty young adults having normal hearing bilaterally and good vision underwent the test. It involved a familiarization list and two lists of 25 independent sentences each. The validation concerned mainly the internal consistency and the equivalence of the lists. Two lists satisfying these criteria are proposed. PMID- 2930366 TI - Frequency-specific auditory brainstem responses. Effective masking levels and relationship to behavioural thresholds in normal hearing adults. AB - Ipsilateral masking levels and normal thresholds for tone pip auditory brainstem responses (ABRs) were investigated in normal subjects for the purpose of establishing recording parameters and norms for frequency-specific tone pip ABR testing. White noise was found to effectively mask ABRs to tone pips at mean signal-to-noise ratios of between -1 and -5.5 dB [dB peak-equivalent (pe) SPL/dB SPL] depending on the tone pip frequency. ABR thresholds were established for tone pips in the presence of ipsilateral masking with high-pass filtered noise for 50-Hz tone pips and notched noise for tone pips from 1,000 to 4,000 Hz, at a nominal signal-to-noise ratio of -5 dB (i.e. with the noise SPL measured prior to filtering). Thresholds occurred between 28.6 and 36.6 dB pe SPL, equivalent to 4.4-8.8 dB nHL. ABR thresholds for masked and unmasked tone pips did not differ significantly. PMID- 2930367 TI - Evoked-response forward-masking functions in chinchillas with noise-induced permanent hearing loss. AB - Evoked-response forward-masking functions were measured by chronic electrodes in the inferior colliculus of the chinchilla before and after exposure to an intense tone that produced a permanent hearing loss. Before exposure, the forward-masking time constants ranged from 50 to 90 ms. After exposure, the forward-masking time constants increased significantly in the region of hearing loss, but not in regions where hearing was normal. The effect of the hearing loss on the time course of forward masking was most pronounced once the hearing loss exceeded 20 25 dB. These physiological changes in the evoked-response forward-masking functions appear to parallel those observed psychophysically in human listeners. PMID- 2930368 TI - Teaching research in post-RN courses. PMID- 2930369 TI - What is an OHN? PMID- 2930370 TI - Nurse and the law. PMID- 2930371 TI - Sunscreen agents. PMID- 2930372 TI - Funding problems in surgical research. PMID- 2930373 TI - Smooth muscle and the surgeon. PMID- 2930374 TI - Common duct exploration or endoscopic sphincterotomy for choledocholithiasis? AB - The relative indications for operative common duct exploration (CDE) and endoscopic sphincterotomy (ES) in treating common duct stones are often unclear. This prospective study compared CDE and ES in treating choledocholithiasis after excluding patients with acute cholecystitis, idiopathic pancreatitis, sphincter of Oddi dysfunction and malignant disease. One hundred and two patients had 105 CDE and a further 50 patients had 57 ES. Of the patients having CDE, 76 also had cholecystectomy for gall-bladder (GB) disease while 26 had prior cholecystectomy. With ES, in 16 the GB was present and not removed while 34 patients had had prior cholecystectomy. Hospitalization was significantly less following ES. There was one peri-operative death after CDE and none after ES. There were two late biliary related deaths, 3 and 27 months after ES, in patients who developed acute cholecystitis. In post-cholecystectomy patients having ES, complications were fewer and less severe after ES (15%) than CDE (41%). In patients with an intact GB, peri-operative complications occurred in 30% after cholecystectomy and CDE. Following ES alone, complications occurred in 33% with the majority of these complications arising from the diseased GB. It is concluded that the optimal treatment for post-cholecystectomy patients with bile-duct stones is ES. In elderly patients with an intact GB, the bile-duct stones can be treated by ES; whether subsequent cholecystectomy is necessary should be assessed on the likelihood of future GB complications. PMID- 2930375 TI - Electrohydraulic lithotripsy for biliary stones. AB - Electrohydraulic lithotripsy was applied in 10 patients with biliary stones which were difficult to extract with the use of choledochoscopy and basket. The difficulties encountered included large impacted stones in the Hartmann's pouch, intrahepatic ducts and lower end of common bile-duct, stones situated at the orifice of acutely angulated segmental bile-ducts and stones impacted just behind strictures. With the use of electrohydraulic lithotripsy all the stones were disintegrated and removed. The only complication was transient haemorrhage from ductal injury. It is concluded that electrohydraulic lithotripsy is a useful adjunct to the choledochoscopic removal of biliary stones. PMID- 2930376 TI - Carcinoid tumours in Auckland, New Zealand. AB - Carcinoid tumours in Auckland diagnosed during 1976-87 have been reviewed retrospectively. Eighty-three patients with carcinoid tumours were seen during this time (56 appendiceal, 11 small bowel, two colorectal, 10 pulmonary and four other). Three patients had carcinoid syndrome. The most common presentation for appendiceal carcinoid was acute appendicitis. The most common presentations for pulmonary lesions were incidental findings on chest X-ray, recurrent chest infection or haemoptysis, while bowel lesions presented with abdominal pain or rectal bleeding. Following resection, 53 of 56 appendiceal patients were alive and well (two died from other causes) and 10 of 10 pulmonary carcinoids were alive and well. In contrast, both patients with colorectal carcinoid died from their disease within 1 year, and, of the patients with small bowel carcinoid, one died of the disease and more than half of the remainder are alive with metastatic spread and symptoms at the time of study. The most important prognostic variables governing outcome were anatomical site of the primary lesion and the state of the histological margins following resection. PMID- 2930377 TI - Management of supracondylar fractures of the femur with Zickel supracondylar nails. AB - Twenty-one cases of supracondylar fracture of the femur treated at St Vincent's Hospital, Melbourne, during 1983-86, by intramedullary Zickel supracondylar nails were reviewed. The causes were high energy trauma in young patients (six), minor trauma in elderly patients (13), and metastatic malignant fracture (two). The functional results were considered excellent in 10, good in six and poor in five. There were two cases of superficial wound infection. All cases united after 3-6 months. The best functional results were in those patients below 60 years or with pathological fractures. It is concluded that internal fixation of supracondylar fractures of the femur with Zickel supracondylar nails is a successful technique and can be performed by open and closed methods. It is most useful in osteoporotic or pathological bone which is unsuitable for bone plating. PMID- 2930378 TI - Displacement of subcapital fractures during internal fixation: a real problem? AB - The potential for femoral head rotation occurring during insertion of a compression hip screw has been investigated. Rotation to up to 30 degrees has been demonstrated, and was not visible on an image intensifier. The insertion of a guide-wire parallel to a hip screw does not control rotation adequately. Small threaded pins do not cause femoral head rotation. PMID- 2930379 TI - Bronchogenic cysts: a persistent dilemma. AB - Bronchogenic cysts are congenital lesions of the respiratory tract. Although usually benign, they have the potential to develop complications and can pose a dilemma in diagnosis and treatment. Twenty patients who presented to the Cardiothoracic Surgical Unit at Royal Prince Alfred Hospital over a 10 year period are reported. Symptoms were common (75%) but serious complications were rare (5%). Most cysts were excised completely at thoracotomy with minimal morbidity. The correct diagnosis was established pre-operatively in less than half of the patients. Therefore excision is recommended to confirm the diagnosis, to exclude malignancy and to minimize possible complications. PMID- 2930381 TI - Abstracts from the annual meeting of the Surgical Research Society of Australasia. Westmead, Sydney, NSW, 15-17 September 1988. PMID- 2930380 TI - Trainee surgery in teaching hospitals: is there a cost? AB - The morbidity rate for 2858 patients undergoing thyroidectomy over the 10 year period January 1977-December 1986 was examined and related to the involvement of a surgical trainee in the operative procedure. There was no overall difference in specific complication rates related to the surgical procedure, being 13.8% when the procedure was undertaken by a consultant, and 13.1% when a surgical trainee was involved in the procedure. There was a significant increase (P = 0.0025) in operative time increasing from 127 min for the consultant to 146 min when the trainee was involved (a 15% increase). There was no significant difference in bed stay for any of the groups. Surgical trainees can be safely taught operative skills under supervision without risk of increased complications. There is a cost, however, to the hospital system in terms of increased demands on time and operative facilities. PMID- 2930382 TI - Continent urinary diversion in a patient with prune belly syndrome and urethral atresia. AB - A case of prune belly syndrome which was managed by left ureterostomy and right nephrectomy during the neonatal period is reported. The patient also had anorectal agenesis with rectovesical fistula, urethral atresia and patent urachus. When the patient was 14 years of age, the urinary diversion was converted to a continent diversion by an antireflux ureteroneocystostomy of both the left and the right ureter together with a right cutaneous ureterostomy. The patient manages very well by clean intermittent catheterization of the right ureterostomy and is fully continent. PMID- 2930383 TI - Cystadenoma of the common bile-duct with malignant transformation. AB - A case of cystadenoma of the common bile-duct with areas of carcinoma in situ in a 61 year old woman is presented. Pre-operative investigations may confuse this rare tumour with the more common choledochal cyst although this case raises the possibility that this neoplasm may have arisen within a longstanding choledochal cyst. Due to the risk of malignant transformation, complete excision of any cystic lesion of the bile-duct is recommended. PMID- 2930384 TI - Responsible drug use. PMID- 2930385 TI - Success for equine wobbler surgery. PMID- 2930386 TI - Characterisation and antimicrobial sensitivity of haemophili isolated from pigs. AB - A total of 70 haemophili from Australia pigs was compared with a range of reference strains of porcine haemophili. Forty-eight of the isolates were identified as Actinobacillus pleuropneumoniae biovar 1 and the remaining 22 isolates as Haemophilus parasuis. Forty one of the A. pleuropneumoniae isolates were used in a study to determine to the minimal inhibitory concentration (MIC) of 12 antimicrobial agents, or combinations of agents. Penicillin, neomycin, trimethoprim, trimethoprim-sulphamethoxazole and tetracycline all showed low MIC values, indicating their potential for the treatment of porcine pleuropneumonia, although 2 isolates showed resistance to tetracycline. A wide range of MIC values was encountered with the sulphonamides. PMID- 2930387 TI - Cerebellar abiotrophy in crossbred cattle. AB - Cerebellar abiotrophy affected 9 of 74 calves sired by a Poll Hereford bull over 2 successive calving seasons. The disease was characterised by episodes of recumbency and ataxia, with hypermetria and wide base stance. Clinical signs commenced between birth and 8 months of age. Two calves which were affected first at 8 months of age recovered clinically 9 months later. Histological lesions were found in the cerebellar cortex of 7 calves and consisted of segmental degeneration and loss of Purkinje cells, and axonal swellings. The clinical signs and pathological findings were consistent with bovine familial convulsions and ataxia, which has not been described previously in Australia. The clinical signs were not attributable to the lesions observed in the cerebellum and an underlying electrophysiological abnormality is proposed. The aetiology of the condition is probably genetic and appears to have a multifactorial basis. PMID- 2930388 TI - The relationship of scrotal circumference to testicular weight in rams. AB - Scrotal circumference (SC), testicular diameter (TD) and testicular weight (TW) were measured at necropsy of 148 Merino rams of varying age (yearling: 110, 2- to 3-year-old: 5, 4-year-old: 28, greater than 7-year-old: 5). These rams, although culled from flocks in north western Queensland for poor conformation or advancing age, had no clinically palpable or gross necropsy lesions of the genitalia. Despite the fact that SC measurement was performed at necropsy on scrota with greatly varying wool cover and its diverse content of plant material (burrs and grass seeds), the correlation of SC with TW was positive, high and significant (r = 0.92, P less than 0.01). This correlation was greater than that between TD and TW (r = 0.91, P less than 0.01) even though both were measured after dissection of the scrotal contents. The clinically convenient SC measurement deserves wider application as an estimate of testicular weight and therefore fertility in rams. PMID- 2930389 TI - Prevalence and intensity of non-strongyle intestinal parasites of horses in northern Queensland. AB - A quantitative post-mortem study of 57 horses from northern Queensland was done to determine the prevalence and intensity of non-strongyle intestinal parasites. The following species (% prevalence) were found: Draschia megastoma (39%); Habronema muscae (43%); Gasterophilus intestinalis (34%), G. nasalis (30%); Parascaris equorum (15%); Strongyloides westeri (6%); Probstmayria vivipara (2%); Oxyuris equi (26%); Anoplocephala magna (2%); A. perfoliata (32%). Mean parasite numbers of individual species ranged from 10 to 1310. Prevalence and intensity data were compared to recent studies in Western Australia and in the United States of America. Differences between stabled and paddocked horses were noted, particularly for botfly larvae and spiruroids. Climatic and seasonal changes in prevalence were restricted to H. muscae, G. nasalis and P. equorum with highest prevalence in the wet season or in horses from wet coastal areas. Only P. equorum showed any age effect being restricted to horses less than 5 years old. Breed and sex of horses was not important. The likelihood of changing parasite population dynamics with improved anthelmintic regimen is discussed. PMID- 2930390 TI - A primary extraskeletal osteogenic sarcoma arising in the spleen of a dog. AB - This paper describes a primary extraskeletal osteogenic sarcoma arising in the spleen of an 11-year-old, male, cross-bred Terrier. Initial diagnosis was made after surgical removal of a splenic mass, at which time the liver and other abdominal viscera appeared grossly normal. However, elevations in the activities of alanine aminotransferase and alkaline phosphatase in blood taken 7 days after laparotomy suggested that hepatic metastases were developing. This was confirmed when the dog died 3.5 months after surgery, with massive hepatic metastatic involvement. There appears to be no previous report of the spleen being the primary site of such a neoplasm in the dog. PMID- 2930391 TI - Some aspects of stray dog behaviour in an urban fringe area. PMID- 2930392 TI - Survey of internal parasites in Western Australian pig herds. 1. Prevalence. AB - Between September 1982 and March 1984, 101 Western Australian piggeries with 15 or more sows were surveyed to determine the prevalence of internal parasites and examine the relationship between parasitism and management practices. Faecal samples were collected from 20 pigs in 4 age groups in randomly selected piggeries, and examined for the presence of eggs of helminth parasites and protozoan cysts. Evidence of nematode parasites was found in 79% of piggeries. Sows were more commonly affected than other classes of pigs with worm eggs being found in 68% of herds. Oesophagostomum spp was the most prevalent worm species, being found in pigs from 65% of piggeries and in sows in 60% of herds. Ascaris suum was the most common species of worm found in growing pigs. There was no evidence of infection with either Metastrongylus spp or Strongyloides spp in any of the herds sampled. Oocysts of coccidia were found in pigs from 56% of piggeries and Balantidium coli cysts were detected in pigs from 42% of piggeries sampled. PMID- 2930393 TI - Survey of internal parasites in Western Australian pig herds. 2. Relationship to anthelmintic usage and parasite control practices. AB - The housing, management and internal parasite control practices used in piggeries in Western Australia was surveyed by interviewing the owner/manager of 100 randomly selected piggeries. At the time of the interview 20 faecal samples were collected from pigs and examined for evidence of internal parasites. Most herds (80%) in which anthelmintics were used, had evidence of nematode infection. Some pig producers were using an anthelmintic that was ineffective against nematode species present while some herds had nematodes that should have been controlled by the anthelmintic being used. Prevalence of nematode infection was higher in pigs run in paddocks than in pigs housed intensively. Washing sows prior to farrowing was associated with a lower prevalence of nematode infection. The findings suggested that pig producers should ensure that the anthelmintic used is effective against the nematodes present in their pigs. It was concluded that administering anthelmintics as a single dose in the feed may not be the most effective method of deworming pigs. PMID- 2930394 TI - Protection against enzootic pneumonia of pigs: intraperitoneal inoculation with live LKR strain of Mycoplasma hyopneumoniae. AB - Pigs obtained from a mycoplasma-free piggery were randomised into 4 groups of 9. Groups 1 and 2 were injected by the intraperitoneal route with liquid culture of the LKR strain of Mycoplasma hyopneumoniae. Group 1 was injected once and group 2 twice. Group 3 was made up of pigs inoculated by the intranasal route with the virulent Beaufort strain of M. hyopneumoniae; they served as the source of infection for the challenge. Group 4 were uninfected, uninjected controls. Six weeks after the last injection, groups from 1 to 4 were placed in contact. Seven of the pigs in the 1-dose group and 6 in the 2-dose group were free of lesions at necropsy 6 weeks after challenge. Of the two pigs with lesions in the 1-dose group one had only a small lesion but the other had extensive lesions; it had not shown an antibody response after injection of culture. The lesions in the 3 pigs in the 2-dose group were all small. All 9 control pigs had lesions which varied from medium to large in size. The difference in the incidence of pneumonia between the injected and control groups was significant (P less than 0.05) and the proportion of severely affected pigs in the vaccinated groups was significantly lower (P greater than 0.01). There was no difference between those given one dose of vaccine and those receiving 2 doses. PMID- 2930395 TI - Pasteurella multocida recovered from live turkeys: prevalence and virulence in turkeys. AB - Swabs of the oropharynges of 801 live turkeys (621 meat birds and 180 breeders), collected from 15 flocks that had experienced an outbreak of fowl cholera and from 12 non-outbreak flocks, were screened for the presence of Pasteurella multocida. Turkeys from outbreak flocks were sampled within 2 to 9 weeks of the outbreak. Forty-nine isolates of P. multocida were recovered from turkeys in 11 of the outbreak flocks, and none were recovered from turkeys in non-outbreak flocks. Isolation rates varied from 0 to 72% of turkeys sampled in a flock. Nineteen isolates were tested for virulence by injecting them intravenously into turkeys, and 14 were lethal. Results demonstrated that for purposes of disease control, meat birds in fowl-cholera-outbreak flocks should be considered carriers of potentially virulent P. multocida for the life of the flock. PMID- 2930397 TI - Separation of avian heterophils from blood using Ficoll-Hypaque discontinuous gradients. AB - Rapid separation of avian heterophils from anticoagulated whole blood was achieved using Ficoll-Hypaque discontinuous gradients. An average of 14.4% of blood heterophils was harvested with a mean purity exceeding 99%. Heterophil viability, as determined by trypan blue dye exclusion, averaged 99.8%. The integrity of isolated heterophils was evaluated by cytochemical staining and ultrastructural examination. Cytochemical staining reactions of heterophils in whole blood and of isolated cell suspensions were similar. No ultrastructural abnormalities were observed. Using this procedure, viable intact heterophils were rapidly isolated from blood with an acceptable cell yield and purity for cell function studies. PMID- 2930396 TI - Status of the 1805 strain of Mycoplasma iowae (K component of serovar I,J,K, N,Q,R) and the SA strain of M. gallopavonis (serovar F). AB - Contrary to historical evidence, recent biochemical and serological studies have suggested that the 1805 strain of M. iowae (K component of serovar I,J,K,N, Q,R) and the SA strain of M. gallopavonis (serovar F) were members of the species M. gallinaceum. After examining three seeds of strain 1805 and an original seed of the SA strain, we present evidence to indicate that 1805 and SA are indeed valid members of the species M. iowae and M. gallopavonis, respectively. However, some seeds of strains 1805 and SA may contain M. gallinaceum. In the case of strain 1805, it is possible that the original seed may have contained M. gallinaceum. PMID- 2930398 TI - Whole-cell protein profiles of Haemophilus paragallinarum as detected by polyacrylamide gel electrophoresis. AB - The soluble whole-cell protein profiles of 15 isolates of Haemophilus paragallinarum were examined using standardized sodium dodecyl sulfate polyacrylamide gel electrophoresis. The patterns were reproducible and the isolates were similar overall. Despite this similarity, two protein profile types were recognized. PMID- 2930399 TI - Lung volume of meat-type chickens. AB - Lung volume (LV) in meat-type chickens was measured by water displacement and was computed as a percentage of body weight (BW). The percentage of LV/BW declined from 2.02 +/- 0.190% at day 1 to 1.38 +/- 0.163% at day 144. Pulmonary hypertension caused by insufficient lung capillary capacity or oxygen exchange area results in right ventricular failure and ascites in meat-type chickens. Insufficient LV in very fast-growing broilers may contribute to this problem. Selection procedures in meat-type chickens should include a method for estimating LV. PMID- 2930400 TI - Monensin toxicity in turkey breeder hens. AB - High mortality in two flocks of 1900 turkey breeder hens accidentally fed 280 g monensin/ton of complete feed is described. Mortality attributed to the poisoning was 76% in flock 1 and 18% in flock 2. Clinically, turkeys were found dead, exhibited respiratory distress with wings extended laterally, had fine tremors, or showed posterior paresis and inability to rise. The most striking finding at necropsy was the almost complete absence of gross lesions. Some turkeys had severely congested lungs; however, many did not. A few birds had pale streaks within the adductor muscles of the legs. Microscopic lesions included myofiber degeneration and necrosis of skeletal and myocardial muscle. Serum phosphorus, lactate dehydrogenase, and creatine phosphokinase were markedly elevated, whereas potassium, chloride, and calcium values were lowered. PMID- 2930402 TI - Isolation of Mycobacterium avium from waterfowl with polycystic livers. AB - An unusual gross appearance of avian tuberculosis, where fluid-filled thin-walled cysts are produced and grossly apparent in preference to granulomas, is presented. Histopathology confirmed the granulomatous nature of the lesions and the presence of intracellular acid-fast organisms. Mycobacterium avium complex was cultured from affected organs. The unusual gross presentation in these cases indicates the need to consider tuberculosis in the differential of cystic diseases of avian livers. PMID- 2930401 TI - Cryptosporidiosis and turkey viral hepatitis in turkeys. AB - Cryptosporidiosis and turkey viral hepatitis were diagnosed in 25-day-old turkeys with increased mortality, enteritis, and stunting. Necropsy lesions included foul smelling, tan-colored, loose feces in the terminal small intestines and ceca. The small intestines and ceca were congested. Multiple white to gray foci were present in the liver and pancreas. Mortality attributed to these conditions was estimated at 4.9%. Microscopic lesions included necrosis with accumulations of macrophages in the liver and pancreas. Bile-duct hyperplasia was present in the livers. Microscopic intestinal lesions consisted of mild to moderate atrophy of the villi of the distal small intestine (ileo-cecal junction) with infiltration of the lamina propria by mononuclear cells. Cryptosporidia were identified and appeared to be attached to villous epithelial cells of the terminal small intestines. Cryptosporidium sp. oocysts were also confirmed by fluorescent microscopic examination of feces stained auramine O. Reovirus was isolated on chicken embryo liver cells from affected livers. PMID- 2930403 TI - Blood concentrations of chlortetracycline in macaws fed medicated pelleted feed. AB - A trial was conducted to determine the suitability of using a pelleted diet containing chlortetracycline (CTC) for treatment of chlamydiosis in macaws. Macaws, normally fed seed and fruit diets in captivity, are notoriously difficult to treat with CTC-medicated mash diets. Healthy macaws fed a pelleted diet containing 1% or 1.5% CTC for 30 or 45 days maintained adequate food intake and mean blood concentrations of 1-2 CTC micrograms/ml blood throughout the treatment period. There were no significant differences between blood concentrations induced by the different dietary CTC concentrations. Blood concentrations of 1 microgram/ml are considered therapeutic, so it is likely that 1% CTC-medicated pellets will be adequate for treating chlamydiosis in these species. PMID- 2930404 TI - Three cases of gastric neoplasia in psittacines. AB - Two adenocarcinomas of the proventriculus and an adenocarcinoma of the ventriculus are described in psittacines. All birds had evidence of digestive tract dysfunction. Hemorrhage into the lumen of the digestive tract from the ulcerated surfaces of the tumors was evident in all birds, either clinically or at necropsy. Radiographic studies, including contrast films, were useful in two cases. Alcian blue and periodic acid-Schiff stains were helpful in determining the origin of the tumor in one case. PMID- 2930405 TI - Experimental and field sulfaquinoxaline toxicosis in Leghorn chickens. AB - Mortality of 47% occurred in a commercial flock of 20-week-old leghorn pullets treated with 0.05% sulfaquinoxaline in the feed. The drug was given for 2-3 days, removed for 2 days, and fed again for 2-3 days. Gross lesions consisted of disseminated hemorrhages, bone marrow pallor, a variety of changes suggesting septicemia, and overwhelming bacterial infection. Experimental feeding of sulfaquinoxaline at 0.05% in the feed at a schedule of 3 days on, 3 days off, and 2 days on successfully reproduced the essential features and gross lesions of the field toxicosis. Mortalities of 32.5% and 43.5% were observed in sulfaquinoxaline treated groups. A high incidence of gangrenous dermatitis occurred in chickens with the experimental toxicosis, but it was not observed in the field case. PMID- 2930406 TI - Light-microscopic lesions associated with naturally occurring bursal cryptosporidiosis in chickens. AB - Information concerning histologic significance of naturally occurring bursal Cryptosporidium sp. infection in chickens was obtained by retrospective examination of histopathology reports and clinical data from histology accessions received during 1986. Cryptosporidiosis was diagnosed in 197 bursas. In two thirds of the accessions, more than 50% of the examined bursas were infected with Cryptosporidium sp. The histologic morphologic lesion diagnosis for Cryptosporidium sp.-infected bursas most often was marked diffuse chronic-active superficial purulent protozoal bursitis with mucosal epithelial hyperplasia. Our study clearly indicates that Cryptosporidium sp. is associated with inflammation and disturbed growth in chicken bursas. Additionally, our data indicate that Cryptosporidium sp. infection is not dependent on bursal damage attributable to other agents, including infectious bursal disease virus. PMID- 2930407 TI - Determination of chicken and turkey plasma and serum protein concentrations by refractometry and the biuret method. AB - Plasma and serum protein concentrations were determined in chickens and turkeys by refractometry (with human and veterinary refractometers) and by the biuret method. Chicken and turkey serum protein values were significantly lower than respective plasma protein values according to both methods. Refractometer readings for both plasma and serum correlated closely with the results of the biuret test (r2 = 0.72 to 0.97). These findings indicate that plasma and serum protein values may be determined accurately in chickens and turkeys with a handheld refractometer. PMID- 2930409 TI - Quality assurance project. PMID- 2930408 TI - Fowl cholera immunity induced by various vaccines in broiler minibreeder chickens determined by enzyme-linked immunosorbent assay. AB - Broiler minibreeder hens were vaccinated for protection against fowl cholera at 12 and 21 weeks of age using several vaccination schemes, which included a live Pasteurella multocida (CU strain) vaccine, two commercial polyvalent fowl cholera oil-based bacterins, and two experimentally prepared polyvalent oil-based bacterins. Some treatment groups received only live or killed vaccines, whereas others received a live vaccine at 12 weeks followed by a killed product at 21 weeks. At 42 weeks of age, all birds that received the live CU vaccine twice or once followed by a bacterin survived challenge. Birds that received killed vaccines only were significantly less protected but still showed a respectable survival rate of 86%. All unvaccinated controls died within 72 hr after challenge. At 72 weeks of age, overall protection was lower than that at 42 weeks, regardless of vaccination treatment. Antibody titers were usually higher in birds that received bacterins than in those receiving live vaccines, yet overall protection was still greater in those birds that received the live cholera vaccine twice. PMID- 2930410 TI - Group process and social climate of GROW, a community mental health organisation. AB - GROW, a community based mutual-help organisation, aims to provide the means for those who have been mentally ill to rehabilitate themselves and grow personally. We measured psychiatric symptoms, group processes, social environment and perceived social support in a sample of GROW group members. We found that GROW does provide the opportunity for and encourages some personal changes and does provide social support. We could not draw any conclusions about GROW's efficacy as a rehabilitative agent. PMID- 2930411 TI - Ganser syndrome in a 10 year old boy--an 8 year follow up. AB - A case of pseudodementia in a 10 year old boy was first reported in 1981. When reviewed 8 years after initial presentation, his symptoms were largely unchanged. The case continues to be complicated by claims for compensation and a successful appeal against the initial compensation judgment. PMID- 2930412 TI - Reserpine withdrawal psychosis. AB - A case of reserpine withdrawal psychosis is reported. This uncommon condition is described as a true withdrawal psychosis and may be due to dopamine receptor supersensitivity. PMID- 2930413 TI - Modifiability of trait anxiety and neuroticism: a meta-analysis of the literature. AB - It is argued that personality scales of neuroticism and anxiety are tapping the same personality trait and that this is a risk factor for neurotic disorders. To see whether this trait is modifiable, a meta-analysis was carried out of therapy outcome studies which included a measure of trait anxiety or neuroticism as a dependent measure. This meta-analysis showed that all psychological therapies are to some extent effective. However, rational-emotive and related therapies produced particularly large reductions in trait anxiety/neuroticism (around 1.25 standard deviations). The possibility that rational-emotive education programmes could be used to lower trait anxiety/neuroticism as a preventive measure is discussed. PMID- 2930414 TI - Australian adolescents' perceptions of their parents. AB - We examined the characteristics of a self-report measure for assessing perceptions of parents, the Parental Bonding Instrument (PBI), in an adolescent community sample (N = 2,147; mean age = 15.4 years). Using factor analysis, three PBI dimensions were identified--the original Care factor and two Protection factors: perceived social control and personal intrusiveness. Important sex differences were found which were not evident in the two factor structure recommended by Parker [1,2]. Relative to sons, daughters saw their fathers as more personally intrusive and their mothers as less socially controlling and much more caring. Overall, adolescents perceived mothers as more caring but more personally intrusive than fathers. Adolescents who saw their father as uncaring and their mother as controlling tended to have the least positive psychosocial profiles. PMID- 2930415 TI - The General Health Questionnaire: reliability and validity for Australian youth. AB - General Health Questionnaire (GHQ) results are given for a large (N = 1013) sample of South Australian young people (average age 19.6 years), to compare the usefulness of the 12-, 28-, and 30-item forms of the GHQ. Internal reliabilities are generally adequate and the Likert scoring method produces significant correlations with psychological measures such as self-esteem. The case-prevalence rate using the binary scoring method was comparable with other studies, but misclassification rates were unacceptably high when DSM-III Axis I diagnosis was used as the criterion for the presence of any psychiatric disorder. PMID- 2930416 TI - Depression and attempted suicide: a comparative study. AB - The Levine-Pilowsky depression questionnaire was used to compare the qualitative and quantitative characteristics of depression in 176 patients admitted to a general hospital following a suicide attempt and 65 psychiatric inpatients with a diagnosis of major affective disorder. The study showed that despite significant age and sex differences there was a striking similarity between the groups on all measures of depression. Diagnostic and therapeutic implications of these findings are discussed, and further research directions are suggested. PMID- 2930417 TI - Re-medicalization and regression in psychiatry. PMID- 2930418 TI - The psychiatric nurse in liaison psychiatry. AB - The role of nursing staff in a liaison consultative unit is by no means established in this country although precedents exist in the United States. Nevertheless, there are clear theoretical reasons for including psychiatric nurses in the liaison team. This report concerns a model of intervention based on one of three models identified in the US studies. The model involves a collaborative/consultative relationship between the psychiatric nurse and the psychiatrist, therefore maximising opportunities for successful intervention and cross-referral. Two clinical vignettes illustrate this. The clinical presentations of 200 patients presenting primarily to the nurse specialist are compared with 200 presenting to the psychiatric department. The patterns of referrals and also the agencies referring differed. The differences in those profiles, together with the management implications, are discussed. High stress areas of nursing, such as cardiology, neurosurgery and haematology, provided a fertile area for referrals to the nurse where referrals to the psychiatrists had not been high. PMID- 2930419 TI - Time to revamp the college training and examination. PMID- 2930420 TI - A tormented mind: clinical and theoretical implications of overwhelming life events. AB - A case study illustrates the aim of this paper, which is to discuss the clinical and theoretical implications of adult patients who have experienced extreme or catastrophic stress in their distant past which may not be immediately "recognisable". A close relationship between Post-Traumatic Stress Disorder and Borderline Personality Disorder (as defined in DSM-III-R) is suggested. PMID- 2930421 TI - Kinematics of U.S. Army helicopter crashes: 1979-85. AB - All records of U.S. Army Class A and B mishaps of four types of helicopters occurring from Oct. 1, 1979, through Sept. 30, 1985, were reviewed for terrain impact kinematic parameters. During this 6-year period, there were 298 mishaps involving 303 aircraft. Approximately 88% of these crashes were considered survivable. Mean and 95th percentile vertical velocity changes at the most severe terrain impact were similar for all aircraft types except the UH-60, which experienced significantly higher impact velocities (p less than 0.001). Overall 95th percentile vertical and horizontal velocity changes at the most severe terrain impact were 11.2 m.s-1 and 25.5 m.s-1, respectively. Both these values are substantially different from values cited in current design standards. Roll, pitch, and yaw attitudes at impact were similar for all aircraft and agreed with the values in current design standards, except that the distribution of roll angles was considerably wider. The importance of using current kinematic parameters for crashworthiness design standards and crash injury prevention is stressed. Recommendations are made to improve crashworthiness design standards. PMID- 2930422 TI - Measuring moment-to-moment pilot workload using synchronous presentations of secondary tasks in a motion-based trainer. AB - A simulation was conducted to determine whether the sensitivity of secondary task measures of pilot workload could be improved by synchronizing their presentation to the occurrence of specific events or pilot actions. This synchronous method of presentation was compared to the more typical asynchronous method, where secondary task presentations are independent of pilot's flight-related activities. Twelve pilots flew low- and high-difficulty scenarios in a motion base trainer with and without concurrent secondary tasks (e.g., choice reaction time, time production). The difficulty of each scenario was manipulated by the addition of 21 flight-related tasks superimposed on a standard approach and landing sequence. Secondary task performance did reflect workload differences between scenarios and among flight segments within scenarios, replicating the results of an earlier study in which the secondary tasks were presented asynchronously. In addition, the choice reaction time secondary task was also sensitive to the workload of specific activities within flight segments. Workload ratings were virtually identical between this and the earlier study. PMID- 2930423 TI - Cognitive demands in automation. AB - As the nature of a task changes with increasing automation, so do the cognitive demands on the human operator. The present study examines the implications of such changes on subjective workload and automation design issues. A variety of tasks (continuous flight control, discrete target acquisition, and decision making) was used to tax the different cognitive systems. Each task could be performed alone or in combination with other tasks. Performance and subjective workload ratings, obtained by three workload scales, were examined as a function of the level of automation. Results demonstrated the usefulness of the multiple resource approach to task analysis. All three workload scales were found to be sensitive to the task demands. The Bedford scale was particularly impressive in distinguishing the different types of resources in demand. Both the multiple resource model's performance predictions and the subjective workload ratings were shown to be invaluable for decisions on how and what to automate. PMID- 2930424 TI - Flight simulator platform motion and air transport pilot training. AB - The influence of flight simulator platform motion on pilot training and performance was examined in two studies utilizing a B-727-200 aircraft simulator. The simulator, located at Ames Research Center, is certified by the FAA for upgrade and transition training in air carrier operations. Subjective ratings and objective performance of experienced B-727 pilots did not reveal any reliable effects of wide variations in platform motion design. Motion platform variations did, however, affect the acquisition of control skill by pilots with no prior heavy aircraft flying experience. The effect was limited to pitch attitude control inputs during the early phase of landing training. Implications for the definition of platform motion requirements in air transport pilot training are discussed. PMID- 2930425 TI - Multidimensional scaling analysis of simulated air combat maneuvering performance data. AB - This paper describes the decomposition of air combat maneuvering by means of multidimensional scaling (MDS). MDS analyses were applied to performance data obtained from expert and novice pilots during simulated air-to-air combat. The results of these analyses revealed that the performance of expert pilots is characterized by advantageous maneuverability and intelligent energy management. It is argued that MDS, unlike simpler metrics, permits the investigator to achieve greater insights into the underlying structure associated with performance of a complex task. PMID- 2930426 TI - Space vehicle approach velocity judgments under simulated visual space conditions. AB - There were 35 volunteers who responded when they first perceived an increase in apparent size of a collimated, two-dimensional perspective image of an Orbiter vehicle. The variables of interest included the presence (or absence) of a fixed reticle within the field of view (FOV), background starfield velocity, initial range to the vehicle and vehicle closure velocity. It was found that: 1) increasing vehicle approach velocity yielded a very small (but significant) effect of faster detection of vehicle movement, nevertheless, response variability was relatively large; 2) including the fixed reticle in the FOV produced significantly slower detection of vehicle radial movement, however this occurred only at the largest range and the magnitude of the effect was only about 15% of the one sigma value; and 3) increasing background star velocity during this judgment led to slower detection of vehicle movement. While statistically significant, this effect was small and occurred primarily at the largest range. A possible explanation for the last two findings is that other static and dynamic objects within the visual field may compete for available attention which otherwise would be available for judging image expansion; thus, the target's retinal image has to expand more than otherwise for its movement to be detected. This study also showed that the Proximity Operations Research Mockup at NASA/Ames can be used effectively to investigate a variety of visual judgment questions related to future space operations. These findings are discussed in relation to previous research and possible underlying mechanisms. PMID- 2930427 TI - The visually guided control of simulated altitude. AB - Simulated "flights" over three different ground textures were used to examine people's ability to extract optical information useful for active regulation of altitude. The textures were regularly spaced lines as follows: 1) orthogonal to the direction of flight (latitude texture); 2) parallel to the direction of flight (meridian texture); and 3) both parallel and orthogonal (square texture). Visual constant velocity forward flight simulations were displayed on a CRT screen, and subjects asked to maintain one of three initial altitudes using a rate control stick. This task was made difficult by the presence of lateral (irrelevant) and vertical (relevant) "wind gusts." The attitude never varied as winds, forward speed, and vertical rate control resulted in only translational movements. Adjusted root mean square errors (ARMSE) showed altitude regulation was more difficult at higher altitudes and when flying over meridian textures. Refined analysis of a single subject's data showed that this was due both to poorer regulation of the vertical wind disturbance and to a tendency to confuse the lateral wind disturbance for a vertical disturbance. PMID- 2930428 TI - Assessing applicants to the NASA flight program for their renal stone-forming potential. AB - Spaceflight could provoke formation of kidney stones, in part by causing hypercalciuria and hyperphosphaturia. Applicants for spaceflight who have metabolic or environmental derangements to begin with might be particularly susceptible to stone formation in space. We, therefore, analyzed 24-h urine samples for stone-forming risk factors in 104 male applicants before their selection into the astronaut-mission specialist corps. The urinary environment was abnormally supersaturated with calcium oxalate in 25.0% of applicants, brushite in 36.5%, and monosodium urate in 66.3%, predisposing these applicants to crystallization of stone-forming calcium salts. This high level of supersaturation was caused by both "metabolic" and environmental disturbances. Thus, hypercalciuria was found in 11.5% of applicants, hyperoxaluria in 2.9%, hyperuricosuria in 18.3% and hypocitraturia in 5.8%. Environmental derangements were generally more prominent, as indicated by low urine volume of less than 2 L.d-1 in 84.6%, high urinary phosphate in 24.4%, and high urinary sodium in 10.6% of applicants. The results suggest that most of the abnormal stone risk factors disclosed among applicants for spaceflight programs were environmental in origin. PMID- 2930429 TI - High-altitude mountaineering and brain function: neuropsychological testing of members of a Mount Everest expedition. AB - Concern has been raised regarding the possibility that hypoxic conditions encountered during high-altitude mountaineering may have lasting harmful effects on the human brain. Members of an expedition to Mount Everest completed a series of neuropsychological tests before and after the expedition. Exposure to altitudes above 7,200 m was limited to a maximum of four consecutive nights, separated by rest periods at lower altitudes. No significant decline in performance was observed on any test. The subjects also completed a short series of tests at different altitudes during the expedition. No significant deterioration was observed at altitudes up to 7,500 m. There do not appear to be lasting harmful effects on brain function under these conditions. PMID- 2930431 TI - Cognitive performance deficits in a simulated climb of Mount Everest: Operation Everest II. AB - Cognitive function at simulated altitude was investigated in a repeated-measures, within-subject study of performance by seven volunteers in a hypobaric chamber, in which atmospheric pressure was systematically lowered over a period of 40 d to finally reach a pressure equivalent to 8,845 m, the approximate height of Mount Everest. The portable cognitive test battery used, Automated Performance Test System (APTS), was specifically designed for field research under adverse environmental conditions as evidenced by compact computer design; automated test administrations, data storage, and retrieval; psychometric properties of stability and reliability; and factorial richness. Significant impairments of cognitive function were seen for three of the five tests in the battery; on two tests, grammatical reasoning and pattern comparison, every subject showed a substantial decrement. The results are discussed in terms of the impact of altitude on specific aspects of cognitive function and the importance of having sensitive and reliable instruments to monitor such effects. PMID- 2930430 TI - The 1988 Louis H. Bauer lecture: the civil space program: theme and variations. PMID- 2930432 TI - Monaural and binaural audiogenic seizures in mice. AB - The progression of sound-induced seizures was examined in unilaterally or bilaterally sensitized SJL/J mice tested either monaurally or binaurally. An unexpected right-side advantage for becoming susceptible to audiogenic seizure was observed. In addition, two distinct patterns of seizure progression were noted, a uniphasic sequence in which a single burst of running preceded the convulsion and a biphasic pattern with two such bursts. The biphasic progression is viewed to be the result of unilaterally initiated seizures and characteristically reached only a clonic level of severity. Uniphasic seizures are concluded to be the result of bilaterally initiated seizures and, when they occurred after more than 30 s of auditory stimulation, frequently reached a tonic level of intensity. The present results support the view that audiogenic seizures are characterized by precisely timed, sequential processes dependent upon the specific priming and test procedures employed. PMID- 2930433 TI - Open-field behavior of spontaneously hypertensive and Wistar-Kyoto normotensive rats: effects of reciprocal cross-fostering. AB - The influence of the maternal environment on the development of open-field behavior in spontaneously hypertensive (SHR) rats was investigated using the technique of reciprocal cross-fostering. Entire litters of SHR and Wistar-Kyoto (WKY) normotensive rats were either reared by their natural mothers, in-fostered to dams of the same strain, or cross-fostered to dams of the opposite strain on the day after birth. Open-field behavior was assessed in male and female rats from the six groups (2 strains x 3 rearing conditions) at 30, 60, 90, and 120 days of age. Animals were observed in the open-field during a 5-min test period and the number of squares entered and hindlimb rears were recorded. At all ages tested, SHR rats were more active in the open field, entering more squares and rearing more frequently than WKYs. SHR females were more active than age-matched SHR males, while no sex differences were apparent in the WKY strain. At each age, open-field behavior was similar across WKY rearing groups. SHR control and in fostered animals responded similarly in the open field; however, SHR cross fostered rats (particularly females) tended to be more active than controls. Although cross-fostering has profound effects on cardiovascular development and functioning in the SHR, it appears that altering the early maternal environment experienced by SHR pups does not grossly affect the development of open-field behavior. PMID- 2930434 TI - Induction of copulatory behavior in Aplysia: atrial gland factors mimic the excitatory effects of freshly deposited egg cordons. AB - Egg laying in the marine mollusc Aplysia is induced and coordinated by peptide products of the egg-laying hormone (ELH) gene expressed in the neuroendocrine bag cells of the central nervous system. At least three structurally related genes, belonging to the ELH family but distinct from the ELH gene, are expressed in the atrial gland, an exocrine organ of unknown function that secretes into the oviduct of Aplysia. The experiments described in this report were designed to test the hypothesis that the atrial gland gene products serve a pheromonal function for the animal, coordinating reproductive behavior among individuals. Our studies showed that there was a significantly shorter latency to copulation when an Aplysia was paired with an animal that was actively laying eggs than when it was paired with a sexually mature but nonlaying animal. Moreover, the addition of extracts or homogenates of the atrial gland to the seawater surrounding two nonlaying animals reduced the latency to mating compared to animals exposed only to seawater or to homogenates of other regions of the reproductive tract, including oviduct. These results suggest that atrial gland products, secreted onto the egg cordon as it passes through the oviduct, may play a pheromonal role and induce mating behavior between individuals. Experiments are in progress to determine whether the active atrial gland factor(s) are products of the ELH family genes expressed in the gland. PMID- 2930436 TI - Spontaneously hypertensive Wistar-derived male rats are more aggressive than those of their normotensive progenitor strain. AB - We compared a group of spontaneously hypertensive rats (SHRs) to a group of Wistar-Kyoto (WKY) rats on each of the three most commonly studied forms of aggressive behavior in rats: muricide, intraspecific aggression, and shock induced fighting (SIF). A significantly higher proportion of SHRs were muricidal; they also fought more at the lowest shock level. A trend for a higher incidence of intraspecific offense behaviors by SHRs was not significant. SHR flinch and jump thresholds were lower than the respective WKY thresholds. Although there were no significant correlations between shock thresholds and any aspects of SIF, the possibility that strain differences in shock sensitivity may contribute to differences in SIF cannot be ruled out. Within strains, there were no correlations among the different forms of aggression. Several different inherited characteristics may be associated with the accentuation of different forms of aggression in SHRs. PMID- 2930435 TI - REM sleep deprivation increases early morning pineal melatonin in castrated rats. AB - Recently nighttime melatonin levels have been shown to be attenuated in depressive patients or patients with dementia of the Alzheimer type. On the other hand, depression can be transiently relieved by deprivation of rapid eye movement sleep. Since exogenous melatonin administration increases rapid eye movement sleep and slow wave sleep in the rat, could rapid eye movement sleep deprivation then inversely influence endogenous melatonin production? We found indices that in castrated Wistar rats 4 days of rapid eye movement sleep deprivation by the cuff pedestal method elevates the pineal content of melatonin by a factor of two at 1 to 2 h after light onset. Rapid eye movement sleep is thus suggested to influence pineal activity. This mechanism might be involved in the human depression-alleviating effect of rapid eye movement sleep deprivation. PMID- 2930437 TI - Effects of combined muscarinic and nicotinic blockade on choice accuracy in the radial-arm maze. AB - Acetylcholine (ACh) systems have been found to be crucial for the maintenance of accurate cognitive performance. A great variety of studies have shown that the muscarinic ACh receptor blocker scopolamine impairs choice accuracy in the radial arm maze. Recently, it has been found that the nicotinic ACh receptor blocker mecamylamine also impairs radial-arm maze choice accuracy. In the present study, we investigated the effects of combined administration of these two ACh blockers. Scopolamine (0.15 mg/kg) and mecamylamine (10 mg/kg) each moderately impaired choice accuracy. Combined treatment with scopolamine and mecamylamine significantly decreased choice accuracy relative to either drug alone. This combination treatment lowered choice accuracy to chance levels. These data show that nicotinic and muscarinic blockade have at least additive effects in producing an anterograde memory deficit. Concurrent blockade of these two components of ACh systems may provide a better animal model of cognitive impairments due to the loss of cholinergic neurons, such as Alzheimer's disease. PMID- 2930438 TI - The effects of unilateral destruction of fimbria-fornix and supracallosal pathways in the rat. AB - Rats with unilateral lesions of either the supracallosal regions (including the dorsal cingulate cortex) and the fimbria-fornix either on the same (S) or the opposite (O) sides of the brain were studied in a 16-hole open field without pharmacologic intervention and, subsequently, after 0.1 and after 1.0 mg/kg scopolamine HBr. Their performances were compared with those of unoperated control animals subjected to the same testing regime. Certain of their behaviors were compared with those of a larger number of animals with bilateral hippocampal destruction (and their control groups) from prior studies. Unilateral lesions of fimbria-fornix and supracallosal afferents to the hippocampal formation produced a decrease in hole poking activity relative to control animals. A further decrease in hole-poking behavior, coupled with increased locomotion, was observed in rats with fimbria-fornix and cingulate cortex lesions on opposite sides of the brain (group O). The smaller dose of scopolamine accentuated these effects. Indeed, the behavior of group O after scopolamine treatment was similar to animals with large bilateral hippocampal lesions. The large dose of scopolamine induced stereotyped rearing or hole poking in the brain-damaged animals but not in the control group. These findings suggest that both the fimbria-fornix and the supracallosal pathway is necessary for normal hippocampal function and that the behavioral deficit is greater when these structures are damaged on the opposite sides of the brain. PMID- 2930439 TI - Anxious mood and memory. AB - Influenced by Bower (Am. Psychol. 36, 129-148, 1981) and Lang (Anxiety and the Anxiety Disorders, Erlbaum, Hillsdale, N.J., 1985), we tested three hypotheses concerning anxious mood and memory: (1) the mood state dependent hypothesis which states that memory retrieval will be greater when mood at encoding and at recall are the same than when they are different: (2) the encoding mood congruent hypothesis which states that information semantically related to mood at encoding is retrieved more readily than information unrelated to mood at encoding; and (3) the recall mood congruent hypothesis which states that information semantically related to mood at recall is retrieved more readily than information unrelated to mood at recall. We induced anxiety in speech anxious students by informing them that they would be delivering a speech during the experiment. Mood could be either anxious or nonanxious at encoding, recall, both, or neither. Hence, there were four groups: Anxiety-Anxiety, Anxiety-Nonanxiety, Nonanxiety-Anxiety, and Nonanxiety-Nonanxiety. Subjects were asked to rate the self-descriptiveness of anxiety (e.g. NERVOUS) and nonanxiety adjective (e.g. POLITE) during the encoding phase, and to recall them later. Anxious mood was measured by self-report scales and by heart rate. No support was obtained for any of the three hypotheses. However, post-hoc analyses indicated that anxiety words were recalled least often in subjects whose heart rate increased from encoding to recall. This suggests that attention to threat information may diminish in aroused nonclinical subjects. PMID- 2930440 TI - Behaviour therapy and obsessional ruminations: can failure be turned into success? AB - This paper considers the possible reasons for the relative failure of behavioural treatment for 'ruminations' (obsessional thoughts without overt compulsive behaviour). It is argued that this problem is due to an inadequate conceptualisation of the nature of ruminations and that as a result, exposure and response prevention have not been applied effectively. Effective treatment of ruminations requires systematically applied exposure in conjunction with the identification and prevention of covert compulsive behaviours. The practical problems of implementing 'covert exposure and response prevention' are considered and a form of habituation training is described, which is designed to overcome these inadequacies. A series of single case studies using this technique is presented. PMID- 2930441 TI - Sensory preconditioning and UCS inflation in human 'fear' conditioning. AB - This study describes a human electrodermal conditioning experiment involving processes of sensory preconditioning and UCS inflation. In stage 1 of the experiment Ss received six presentations of a CS+ paired with an innocuous 65 dB tone (UCS) and six presentations of an unpaired CS-. In stage 2, Ss in the experimental group had the aversiveness of the UCS inflated as the intensity of the 65 dB tone was increased to 115 dB. In stage 3, Ss were given test presentations of CS+ and CS-. A differential CR to CS+ was found only in stage 3 of the experiment and only in Ss who had experienced the UCS inflation procedure. These results suggest that (i) sensory preconditioning had occurred in stage 1 despite the failure to observe a differential CR in this stage, and (ii) the differential CR observed in stage 3 was mediated by an internal representation of the UCS whose aversiveness had been inflated in stage 2. As well as confirming that processes of sensory preconditioning and UCS inflation can be observed in human as well as animal Ss, these findings have important implications for contemporary conditioning models of clinical fears. In particular, they suggest that a contemporary conditioning model of acquired fears is not bound by the need to discover contiguous stimulus-trauma experiences in the histories of clinical phobias since, in humans at least, processes of stimulus association and UCS revaluation appear to be relatively independent. PMID- 2930442 TI - Factors influencing drinking behavior in alcoholic panickers and non-panickers. AB - Male alcoholics who (a) experienced panic attacks prior to abusing alcohol, (b) experienced panic attacks subsequent to abusing alcohol, and (c) had not experienced panic attacks were compared on three sets of measures: the Panic Attack Questionnaire, the Restrained Drinking Scale, and the Inventory of Drinking Situations. The results showed that two groups of Ss who experienced panic attacks were more likely than non-panickers to use drugs other than alcohol, began drinking at an earlier age, had a greater proportion of parents with panic and alcohol related problems, had higher drinking restraint scores, and drank in more situations. The Ss who experienced panic attacks prior to abusing alcohol were more likely than the other groups to drink in situations similar to those related to agoraphobic fears. It was postulated that alcoholics who experience panic attacks, especially those who experienced panic attacks prior to abusing alcohol may be using alcohol to reduce anxiety or fear related to panic attacks. PMID- 2930443 TI - Research-structured vs clinically flexible versions of social learning-based marital therapy. AB - The purpose of this study was to compare our structured research-based version of marital therapy from a social learning perspective with a clinically flexible version of the same treatment where treatment plans were individually-based and there was no specific number of treatment sessions. Thirty distressed married couples were randomly assigned to one of these two treatments. Assessment of outcome was based on global marital satisfaction, spouse reports of functioning in specific areas, and direct observational measures of communication. At posttest there were no differences in efficacy between structured and flexible treatments, although both treatments led to significant improvements. At a 6 month follow-up couples treated with the structured format were more likely to have deteriorated and flexibly treated couples were more likely to have maintained their treatment gains. PMID- 2930444 TI - Cognitive bias and irrational belief as predictors of avoidance. AB - Cognitive bias, i.e. overestimates of subjective probability and cost of catastrophic events, and irrational belief were explored as predictors of avoidance. Three groups-anxiety disordered clients, a mixed group of clinic outpatients, and normals--were administered several self-report inventories. Multiple regression analyses were used to investigate a modified version of the Agoraphobic Cognitions Questionnaire, the Belief Scale, and the Body Sensations Questionnaire as predictors of avoidance, as measured by the Mobility Inventory. It was hypothesized that frequency x probability x cost of catastrophic cognitions (and the occurrence of the events they represent) would be a better predictor of avoidance than frequency alone. It was also hypothesized that irrational thinking would be a significant predictor of avoidance. The results generally supported the hypotheses, with subjective probability emerging as a particularly potent predictor of avoidance. Theoretical and clinical implications are discussed. PMID- 2930445 TI - Sensations, cognitions and the perception of cues associated with expected and unexpected panic attacks. AB - Panic attacks may be perceived by patients as either cued or uncued (spontaneous) and either expected or unexpected. The purpose of the present study was to examine the prevalence and characteristics of these types of panic. Twenty-six panic disorder patients with mild avoidance and 18 with moderate or severe avoidance were instructed to complete a questionnaire during or immediately following each of three consecutive naturally occurring panic attacks they experienced. They were asked to rate the extent to which they expected the panic attack to occur, whether they felt it was associated with an external panic "cue" (e.g. a shopping mall), whether they would expect to panic again in similar circumstances, their mood, present level of life stress, and fear and severity of their body sensations and disturbing cognitions. Results indicated that from a sample of 92 questionnaires, each representing a separate panic, nearly 70% of panic attacks were rated as cued-expected and only one panic was rated as uncued expected. The other two categories each comprised about 15% of all panic attacks. There were few reported differences in body sensations and cognitions reported as a function of type of panic and no differences with regard to extent of agoraphobic avoidance. Expected panic was associated with a higher expectation of future panic in similar circumstances. PMID- 2930446 TI - Selective recall of surprising visual scenes. An experimental note on Seligman and Yellen's theory of dreams. AB - Seligman and Yellen (Behav. Res. Ther. 25, 1-24, 1987) reported that dream fragments that are unrelated to the preceding fragments of the same dream are recalled as being more vivid and colorful and are remembered in more detail than dream fragments that are plot related and that lack an element of surprise. The authors take this as support for their hypothesis that while one dreams, two distinct types of visualization occur: one consisting of sudden, emotional bursts and the other occurring as a product of cognitive integration. An alternative explanation of Seligman and Yellen's data is that surprisingness of visual scenes is, in itself, sufficient to produce vivid, detailed, and colorful recall. In order to test this alternative hypothesis, 239 volunteers evaluated target slides that were preceded by either related or unrelated slides. When preceded by unrelated slides, the target slide was experienced as more surprising, was forgotten less often, and was evaluated as more colorful, more detailed, and more vivid. It is concluded that the data given by Seligman and Yellen do not constitute unequivocal support for their hypothesis. PMID- 2930447 TI - An evaluation of the Takeda UA751 automatic sphygmomanometer. AB - The Takeda UA751, a simple automatic blood pressure measuring device, was compared with standard osciltatory measurement. There was little or no systematic difference in pressure determined by the automatic or manual method and the correlation between the two devices for both systolic and distolic pressure was satisfactory. This suggests that the Takeda UA751 is an appropriate device for patient self monitoring of blood pressure or as a measure of pressure in group outcome trials. The results essential replicate an evaluation by Steptoe and Molineux (Behav. Res. Ther. 24 223-226, 1986) of an earlier version of the Takeda (the Copal UA251) that used a different method for determining blood pressure. PMID- 2930448 TI - Safety-signal therapy in agoraphobics: a preliminary test. AB - It has been argued that persistent avoidance behaviour is strongly influenced by safety signals, and that agoraphobic avoidance behaviour is a clinical example of this influence. It was proposed that agoraphobic avoidance can be reduced by the judicious use of safety signals, and specifically, by training patients to travel towards rather than away from safety. A safety-signal technique in which the patient travelled towards the therapist at the most fear-inducing situations was compared with conventional therapist-assisted exposure. In the second part of the treatment programme, both groups of agoraphobics were given homework assignments. The safety-signal technique resulted in slightly better clinical gains than those achieved by therapist assisted exposure, but after these relatively brief programmes, the improvements in both groups were weak. Global clinical outcome was influenced by age, chronicity and long-term benzodiazepine use. PMID- 2930449 TI - [Characterization of Campylobacter spp. from wild birds]. AB - Bacteria of the genus Campylobacter were isolated from 28 Rooks (Corvus frugilegus), 1 Red Kite (Milvus milvus), 1 Lapwing (Vanellus vanellus), 1 Coot (Fulica atra), 1 Common Moorhen (Gallinula chloropus) and 1 Northern Mallard (Anas platyrhynchos). Altogether, C. jejuni biovar 1, was isolated 19x, C. jejuni biovar 2 8x and C. coli 5x. Among C. jejuni biovar 1 and 2 there were 5 isolates tolerating a content of 1.5% NaCl in the medium. H2S proof of 3 C. jejuni biovar 2 and 1 C. coli isolates resulted positive or negative dependent on incubation time of the used bacterial inoculum. Concerning Rooks the findings indicate that nestlings are more often infected with campylobacters than older birds. Only 1 campylobacter isolate could be recovered from altogether 54 birds of prey although 16 Buzzards (Buteo buteo) were investigated as nestlings. PMID- 2930450 TI - [The effect of the time of day on the renal excretion of several minerals in cattle]. AB - Urine of 17 cows was totally collected with a permanent bladder catheter for 3-5 days. The quantities of excreted calcium, magnesium, sodium, potassium, and inorganic phosphorus were evaluated. In a second experiment 448 urine samples, spontaneously excreted at different times of day, were analysed concerning the concentrations of the specified minerals and of creatinine. In order to avoid a possible misinterpretation the relations of the concentrations of the minerals and of creatinine concentration in each sample were computed. In both experiments it is shown that excretion of potassium and magnesium doesn't considerably differ at different times of day. Calcium, sodium and inorganic phosphorus, however, show maxima of excretion in the middle of each day and minima at midnight. Possible reasons for this phenomena and the meaning for use in diagnosis are discussed. PMID- 2930451 TI - [The prevention of distemper in zoo animals]. AB - The distemper virus infection of different non-domestic carnivorous zoo animals is known since long. All species involved belonged to the suborder Fissipedia. In 1988 a distemper or morbillivirus-like infection occurred in harbour seals, a member of the suborder pinnipedia. For the prophylaxis of distemper in dogs attenuated live vaccines are commonly used. In zoo animals, however, these vaccines caused distemper several times. In contrast, an inactivated virus vaccine proved both its safety and efficacy in more than hundred zoo animals of various species. PMID- 2930452 TI - [Computer simulation of the stable climate on the PC in veterinary practice]. AB - The wide distribution of personal computers allows the application of programs which enable veterinary surgeons to assist in the management of live stock. A simulation model is made for the field of indoor climates of stables which makes a full-year calculation of temperature and humidity of the indoor climate and the quality of the air in stables. The calculation is based on a steady-state balance model of energy (heat and humidity) and matter. Using the example of a pig fattening sty, all the necessary system parameters are stated that are needed to totally present the model. The results of the simulation are then interpreted. Furthermore the assertions and conclusions will be shown which result thereby. PMID- 2930453 TI - Characteristics necessary for an interconvertible enzyme cascade to generate a highly sensitive response to an effector. AB - A monocyclic interconvertible enzyme cascade, in which active and inactive states of an enzyme are interconverted by two opposing enzyme-catalysed reactions, does not necessarily produce a greater degree of sensitivity to an effector than one could expect from direct interaction between effector and target reaction. On the contrary, a cascade in which an effector acts on one of the enzymes catalysing the interconversion reactions by altering the apparent value of its specificity constant will always generate a less sensitive response than direct interaction would give. Nonetheless, even if both interconversion reactions obey Michaelis Menten kinetics with the ordinary types of inhibition and activation, one can easily generate an enormous sensitivity in which a 0.5% change in concentration can increase the proportion of target enzyme in the active state from 10% to 90%: this corresponds approximately to a Hill coefficient of 800. To maximize the sensitivity, the following conditions must be satisfied: (1) both modifier enzymes must act under conditions of near saturation; (2) the effector must act on both of them in opposite directions; (3) it must alter the apparent values of their catalytic constants; (4) the enzyme subject to inhibition by the effector must respond at much lower effector concentrations than the enzyme subject to activation. As the last of these conditions appears to be counter-intuitive, it suggests that feeble activation of modifier enzymes in real systems may have passed unnoticed, or been dismissed as physiologically insignificant, although in reality crucial to the effective response of the system. PMID- 2930454 TI - Chondroitinase ABC digestion of dermatan sulphate. N.m.r. spectroscopic characterization of the oligo- and poly-saccharides. AB - Dermatan sulphates, in which iduronate was the predominant uronate constituent, were partially digested by chondroitinase ABC to produce oligosaccharides of the following structure: delta UA-[GalNAc(4SO3)-IdoA]mGalNAc(4SO3) [where m = 0-5, delta UA represents beta-D-gluco-4-enepyranosyluronate, IdoA represents alpha-L iduronate and GalNAc(4SO3) represents 2-acetamido-2-deoxy-beta-D-galactose 4-O sulphate], which were fractionated by gel-permeation chromatography and examined by 100 MHz 13C-n.m.r. and 400/500 MHz 1H-n.m.r. spectroscopy. Experimental conditions were established for the removal of non-reducing terminal unsaturated uronate residues by treatment with HgCL2, and reducing terminal N acetylgalactosamine residues of the oligosaccharides were reduced with alkaline borohydride. These modifications were shown by 13C-n.m.r. spectroscopy to have proceeded to completion. Assignments of both 13C-n.m.r. and 1H-n.m.r. resonances are reported for the GalNAc(4SO3)-IdoA repeat sequence in the oligosaccharides as well as for the terminal residues resulting from enzyme digestion and subsequent modifications. A full analysis of a trisaccharide derived from dermatan sulphate led to the amendment of published 13C-n.m.r. chemical-shift assignments for the polymer. PMID- 2930455 TI - Ectoenzymes of the kidney microvillar membrane. Affinity purification, characterization and localization of the phospholipase C-solubilized form of renal dipeptidase. AB - Renal dipeptidase (EC 3.4.13.11) was solubilized from pig kidney microvillar membranes with bacterial phosphatidylinositol-specific phospholipase C and then purified by affinity chromatography on cilastatin-Sepharose. The enzyme was apparently homogeneous on SDS/polyacrylamide-gel electrophoresis with an Mr of 47,000. Immunohistochemical analysis of the distribution of the dipeptidase showed it to be concentrated in the brush-border region of the proximal tubules in close association with endopeptidase-24.11) (EC 3.4.24.11). The purified dipeptidase was shown to contain 1 mol of inositol/mol and to possess the cross reacting determinant characteristic of the glycosyl-phosphatidylinositol membrane anchoring domain. The glycoprotein nature of renal dipeptidase was confirmed by chemical and enzymic deglycosylation. These results establish renal dipeptidase as a glycosyl-phosphatidylinositol-anchored ectoenzyme of the microvillar membrane. PMID- 2930456 TI - Purification of a growth factor related to platelet-derived growth factor and a type beta transforming growth factor secreted by mouse neuroblastoma cells. A general strategy for the purification of basic polypeptide growth factors. AB - A general strategy was developed for the purification of basic polypeptide growth factors. This method is a combination of gel filtration, weak-cation-exchange h.p.l.c. and reverse-phase h.p.l.c., separating the proteins according to size, charge and hydrophobicity respectively. All steps are carried out at low pH with exclusively volatile acidic buffer solutions. The sterile conditions and easy removal of salt by freeze-drying facilitate the detection of the growth factors by biological assays. By using this method, homogeneous preparations of two basic growth factors were purified in high yield from mouse-neuroblastoma-Neuro-2A-cell conditioned medium. It is shown that these purified factors are biochemically and immunologically related to platelet-derived growth factor and type beta transforming growth factor from human platelets. PMID- 2930457 TI - Interaction with a monoclonal antibody alters the expression of co-operativity by phenylalanine hydroxylase from rat liver. AB - Phenylalanine hydroxylase purified from rat liver shows positive co-operativity in response to variations in phenylalanine concentration when assayed with the naturally occurring cofactor tetrahydrobiopterin. In addition, preincubation of phenylalanine hydroxylase with phenylalanine results in a substantial activation of the tetrahydrobiopterin-dependent activity of the enzyme. The monoclonal antibody PH-1 binds to phenylalanine hydroxylase only after the enzyme has been preincubated with phenylalanine and is therefore assumed to recognize a conformational epitope associated with substrate-level activation of the hydroxylase. Under these conditions, PH-1 inhibits the activity of phenylalanine hydroxylase; however, at maximal binding of PH-1 the enzyme is still 2-3 fold activated relative to the native enzyme. The inhibition by PH-1 is non competitive with respect to tetrahydropterin cofactor. This suggests that PH-1 does not bind to an epitope at the active site of the hydroxylase. Upon maximal binding of PH-1, the positive co-operativity normally expressed by phenylalanine hydroxylase with respect to variations in phenylalanine concentration is abolished. The monoclonal antibody may therefore interact with phenylalanine hydroxylase at or near the regulatory or activator-binding site for phenylalanine on the enzyme molecule. PMID- 2930458 TI - Solubilization of stable adenosine A1 receptors from rat brain. AB - Despite numerous reports of solubilization of adenosine A1 receptors, little progress has been made in isolating or purifying the receptor, owing to the extreme lability of the preparations. The present solubilization strategies recognized the possible role of endogenous adenosine to produce adenosine receptor-N-protein complexes, which are intrinsically unstable, and instead attempted to use caffeine to solubilize free adenosine receptors, which might be more stable. Endogenous adenosine was removed from membranes by using adenosine deaminase along with GTP to accelerate the release of receptor-bound adenosine. The receptors were then occupied with caffeine and solubilized with 3-[(3 cholamidopropyl)-dimethylammonio]-1-propanesulphonate (CHAPS) in the presence of glycerol. These soluble preparations exhibited the characteristics of free adenosine receptors. They bound the A1-selective antagonist 8-cyclopentyl-1,3 dipropylxanthine (CPDPX) with high affinity to a single class of binding sites, which were insensitive to GTP. The binding activity was extremely stable, with a half-life of about 5 days at 4 degrees C; there was little change in either receptor number or affinity during 3 days at 4 degrees C. This methodology should greatly facilitate the characterization, isolation and purification of the adenosine A1 receptor. PMID- 2930459 TI - Analysis of kinetic data for irreversible enzyme inhibition. AB - Many organophosphorus compounds are irreversible inhibitors of acetylcholinesterase. The methods used in the literature to determine the inhibition kinetic constants usually involve either manual determination of the slope at various points along the inhibition progress curve or fitting polynomials to the curve. The present study investigates the use of non-linear regression analysis to determine the various parameters. A method is suggested that yields accurate values for the inhibition constants under a range of circumstances. PMID- 2930460 TI - Caprine acrosin. Purification, characterization and proteolysis of the porcine zona pellucida. AB - Acrosin purified from an acidic extract of ejaculated goat spermatozoa migrated as a single 42,000-Mr band in SDS/polyacrylamide-gel electrophoresis. Reduction and alkylation of caprine acrosin produced two polypeptides, one of Mr 40,000 (heavy chain) and the other of Mr 3700 (light chain). The light chain purified by reversed-phase h.p.l.c. was a glycosylated octadecapeptide with an amino acid sequence similar to that of the N-terminal 18 residues of porcine acrosin light chain (78% positional identity). The sequence of the N-terminal 37 amino acids of purified caprine acrosin heavy chain is similar to that of porcine acrosin heavy chain (70% positional identity through 37 residues). Studies with synthetic substrates and synthetic and natural proteinase inhibitors confirmed both the specificity of the purified proteinase for Arg-Xaa and Lys-Xaa bonds and a serine proteinase mechanism. Purified caprine acrosin hydrolysed the 90 kDa and 65 kDa components, but did not hydrolyse the 55 kDa component of the porcine zona pellucida. The action of the enzyme on the porcine zona pellucida was indistinguishable from that previously reported for porcine acrosin. PMID- 2930461 TI - Human intestinal glutathione S-transferases. AB - Cytosolic glutathione S-transferases were purified from the epithelial cells of human small and large intestine. These preparations were characterized with regard to specific activities, subunit and isoenzyme composition. Isoenzyme composition and specific activity showed little variation from proximal to distal small intestine. Specific activities of hepatic and intestinal enzymes from the same patient were comparable. Hepatic enzymes were mainly composed of 25 kDa subunits. Transferases from small intestine contained 24 and 25 kDa subunits, in variable amounts. Colon enzymes were composed of 24 kDa subunits. In most preparations, however, minor amounts of 27 and 27.5 kDa subunits were detectable. Separation into isoforms by isoelectric focusing revealed striking differences: glutathione S-transferases from liver were mainly basic or neutral, enzymes from small intestine were basic, neutral and acidic, whereas large intestine contained acidic isoforms only. The intestinal acidic transferase most probably was identical with glutathione S-transferase Pi, isolated from human placenta. In the hepatic preparation, this isoform was hardly detectable. The specific activity of glutathione S-transferase showed a sharp fall from small to large intestine. In proximal and distal colon, activity seemed to be about equal. In the ascending colon there might be a relationship between specific activity of glutathione S transferases and age of the patient, activity decreasing with increasing age. PMID- 2930462 TI - Synthesis and processing of cathepsin L, an elastase, by human alveolar macrophages. AB - Cathepsin L was partially purified from lysates of freshly isolated macrophages lavaged from lungs of apparently healthy adults and found to be chromatographically and catalytically identical with liver cathepsin L. Western blotting analysis showed that lung macrophages contain significant levels of a precursor of cathepsin L (43 kDa) in addition to mature enzyme (25 kDa). After culturing for a further 24 h, the precursor disappeared and a new band, corresponding to 34 kDa, appeared, suggesting that the precursor had been processed to an intermediate form of cathepsin L. Biosynthetic labelling of macrophages in vitro with [35S]methionine followed by immunoprecipitation with the cathepsin L antibody confirmed that the cells synthesize cathepsin L as a 43 kDa precursor that is then processed to the mature form (25 kDa) via a 34 kDa intermediate. The precursor, but not the processed forms, was released into the culture medium. During culture in vitro the 34 kDa intermediate accumulated, and little enzyme was processed to the 24 kDa form, consistent with the immunoblot data. Human lung macrophages contain a 1.5 kb transcript of cathepsin L mRNA, whereas none is detectable in human monocytes. These results establish that differentiation of human macrophages within the lung is accompanied by synthesis and expression of an elastinolytic enzyme, cathepsin L. The altered processing of cathepsin L observed during cultivation in vitro suggests caution in the assessment of the elastinolytic potential of human macrophages based on assay in vitro. PMID- 2930463 TI - Purification and N-terminal partial sequence of anti-epilepsy peptide from venom of the scorpion Buthus martensii Karsch. AB - An anti-epilepsy peptide (AEP) was isolated and purified from venom of the scorpion Buthus martensii Karsch. The purification procedure included CM-Sephadex C-50 chromatography, gel filtration on Sephadex G-50 and DEAE-Sephadex A-50 chromatography. Its homogeneity was demonstrated by pH 4.3 polyacrylamide-disc gel electrophoresis, focusing electrophoresis and SDS/polyacrylamide-disc-gel electrophoresis. The Mr of this peptide, calculated from measurements in SDS/15% polyacrylamide-disc-gel and SDS/20%-polyacrylamide-disc-gel electrophoresis, is 8300. The isoelectric point is 8.52 by pH 8-9.5-range isoelectric focusing. No haemorrhagic or toxic activities were found. No toxicity was found even after the dose reached 28 mg/kg. The pharmacological tests showed that the AEP had no effect on heart rate, blood pressure or electrocardiogram, but strongly inhibited epilepsy induced by coriaria lactone and cephaloridine. The fluorescence spectrum showed that the peptide has a strong emission peak at 337 nm. Amino acid analysis suggested that the AEP is composed of 66 residues from 18 amino acids and has an Mr of 8290. The sequence of the first 50 N-terminal residues is as follows: Asp Gly-Tyr-Ile-Arg-Gly-Ser-Asp-Asn-Cys-Lys-Val-Ser-Cys-Leu-Leu-Gly-Asn- Glu-Gly - Cys-Asn-Lys-Glu-Cys-Arg-Ala-Tyr-Gly-Ala-Ser-Tyr-Gly-Tyr-Cys-Trp-Thr-Val- Lys-Leu Ala-Gln-Asp-Cys-Glu-Gly-Leu-Pro-Asp-Thr-. PMID- 2930464 TI - The effects of fasting or hypoxia on rates of protein synthesis in vivo in subcellular fractions of rat heart and gastrocnemius muscle. AB - We measured rates of protein synthesis in vivo in subcellular fractions (soluble, myofibrillar and stromal fractions) of the heart and the gastrocnemius from rats after fasting or under hypoxic conditions (i.e. atmospheres containing 5% or 10% O2). Such interventions are known to inhibit protein synthesis under some circumstances. The recovery of tissue protein after fractionation was 80-100%. The proportions of protein present in the soluble and stromal fractions were different in the two muscles. The rates of protein synthesis in the myofibrillar and stromal fractions were less than those for total mixed tissue protein, whereas the rate for soluble protein was greater. Both fasting and moderate hypoxia (10% O2 for 24 h) inhibited protein synthesis in the gastrocnemius. In this tissue, the synthesis of the myofibrillar fraction was apparently the most sensitive to inhibition, and this resulted in some significant increases in the soluble-fraction/myofibrillar-fraction protein-synthesis rate ratios. In the heart, fasting inhibited protein synthesis, but moderate hypoxia (10% O2 for 24 h) did not. The rate of protein synthesis in the cardiac myofibrillar fraction was again more sensitive to fasting than were the rates in the other fractions, but it was not as sensitive as that in the gastrocnemius. Under severely hypoxic conditions (5% O2 for 1 or 2 h), protein synthesis was decreased in all fractions in both tissues. These results suggest that the rates of protein synthesis in these relatively crude subcellular fractions vary. PMID- 2930466 TI - Kinetics of p-nitrophenyl pivalate hydrolysis catalysed by cytoplasmic aldehyde dehydrogenase. AB - The effects of modifiers (NAD+, NADH, propionaldehyde, chloral hydrate, diethylstilboestrol and p-nitrobenzaldehyde) on the hydrolysis of p-nitrophenyl (PNP) pivalate (PNP trimethylacetate) catalysed by cytoplasmic aldehyde dehydrogenase are reported. In each case a different inhibition pattern is obtained to that observed when the substrate is PNP acetate; for example, propionaldehyde and chloral hydrate competitively inhibit the hydrolysis of PNP acetate, but are mixed inhibitors with PNP pivalate. The kinetic results can be rationalized in terms of different rate-determining steps: acylation of the enzyme in the case of the pivalate but acyl-enzyme hydrolysis for the acetate. This is confirmed by stopped-flow studies, in which a burst of p-nitrophenoxide is observed when the substrate is PNP acetate, but not when it is the pivalate. PNP pivalate inhibits the dehydrogenase activity of the enzyme competitively with the aldehyde substrate; this is most simply explained if the esterase and dehydrogenase reactions occur at a common enzymic site. PMID- 2930465 TI - Purification and kinetic mechanism of the major glutathione S-transferase from bovine brain. AB - The major glutathione S-transferase isoenzyme from bovine brain was isolated and purified approx. 500-fold. The enzyme has a pI of 7.39 +/- 0.02 and consists of two non-identical subunits having apparent Mr values of 22,000 and 24,000. The enzyme is uniformly distributed in brain, and kinetic data at pH 6.5 with 1 chloro-2,4-dinitrobenzene (CDNB) as substrate suggest a random rapid-equilibrium mechanism. The kinetics of inhibition by product, by GSH analogues and by NADH are consistent with the suggested mechanism and require inhibitor binding to several different enzyme forms. Long-chain fatty acids are excellent inhibitors of the enzyme, and values of 1nKi for hexanoic acid, octanoic acid, decanoic acid and lauric acid form a linear series when plotted as a function of alkyl chain length. A free-energy change of -1900 J/mol (-455 cal/mol) per CH2 unit is calculated for the contribution of hydrophobic binding energy to the inhibition constants. The turnover number of the purified enzyme dimer is approx. 3400/min. When compared with the second-order rate constant for the reaction between CDNB and GSH, the enzyme is providing a rate acceleration of about 1000-fold. The role of entropic contributions to this small rate acceleration is discussed. PMID- 2930467 TI - The action of cytoplasmic aldehyde dehydrogenase on methyl p-nitrophenyl carbonate and p-nitrophenyl dimethylcarbamate. AB - Cytoplasmic aldehyde dehydrogenase catalyses the hydrolysis of methyl p nitrophenyl (PNP) carbonate at an appreciable rate that is markedly stimualted by NAD+ or NADH. The nuleotides accelerate the rate-limiting hydrolysis of the acyl enzyme intermediate while slowing the observed burst of p-nitrophenoxide production. With PNP dimethylcarbamate the enzyme catalyses the slow release of approx. 1 molecule of p-nitrophenoxide per tetrameric enzyme molecule; during the reaction the enzyme becomes effectively inactivated, as the rate of hydrolysis of the acyl-enzyme is virtually zero. The presence of NAD+, NADH, propionaldehyde, chloral hydrate, diethylstilboestrol or disulfiram slows the reaction of enzyme with PNP dimethylcarbamate. The reaction appears to be dependent on a group of pKa 7.6, possibly a cysteine residue. The effect of PNP dimethylcarbamate on the dehydrogenase activity of the enzyme is consistent with there being a single type of active site for the enzyme's dehydrogenase and esterase activities. Steric and electronic factors that govern reaction of the enzyme with PNP substrates are discussed. PMID- 2930468 TI - The binding of NADH to cytoplasmic aldehyde dehydrogenase after modification with p-nitrophenyl dimethylcarbamate. AB - Cytoplasmic aldehyde dehydrogenase may be modified by reaction with p-nitrophenyl dimethylcarbamate to give a stable E-X-CO-NMe2 species that is an analogue of the usual labile acyl-enzyme involved in the enzyme's reactions. [X is derived from an enzymic nucleophilic group.] This species still contains the tightly bound NADH that is present in the native enzyme. When further NADH binds to E-X-CO-NMe2 its fluorescence is enhanced over 4 times more than when it binds to unmodified enzyme; this fluorescence is completely unaffected by high propionaldehyde concentration and only slightly affected by p-nitrobenzaldehyde. The modified species has 1.0 NADH binding site in the absence of Mg2+ and 1.67 sites in its presence. The rate of dissociation of E-X-CO-NMe2.NADH is biphasic (k 3.4 and 1.8 min-1) and is considerably lower than that of E.NADH; the presence of Mg2+ slows the process even more (k 0.47 and 0.37 min-1). The implications of these studies towards a greater understanding of the nature of aldehyde dehydrogenase-catalysed reactions are discussed. PMID- 2930469 TI - Incorporation of atmospheric oxygen into the carbonyl functionality of the protochlorophyllide isocyclic ring. AB - Detached cucumber (Cucumis sativus L. var. Beit Alpha) cotyledons incubated in darkness with 5-aminolaevulinic acid and either 16O2 air (control) or 18O2 in N2 accumulated protochlorophyllide. This was converted into methyl phaeoporphyrin alpha 5 and analysed by mass spectrometry. The molecular ion of the methyl phaeoporphyrin alpha 5 derived from the 18O2 incubation was 2 mass units greater than that of the control, establishing that the oxo oxygen atom of the isocyclic ring is derived from atmospheric oxygen. PMID- 2930471 TI - Comparison of the flux of carbon to hepatic glycogen deposition and fatty acid and cholesterol synthesis on refeeding rats fed ad libitum or meal-fed rats with a chow-diet meal. AB - Meal-fed rats and rats fed ad libitum had similar rates of hepatic glycogen deposition on refeeding with a chow meal. In contrast, the rate of hepatic lipid synthesis (cholesterol plus fatty acids) was 6-fold higher on refeeding in the meal-fed group compared with the 'ad libitum' group. There were no significant differences in the gastrointestinal or hepatic contents of glucose or lactate between the two groups. It is suggested that in the meal-fed group exogenous glucose may be directly converted into glycogen, whereas the substrate for lipid synthesis is a C3 unit. PMID- 2930470 TI - Detection of peroxyl and alkoxyl radicals produced by reaction of hydroperoxides with rat liver microsomal fractions. AB - E.s.r. spin trapping using the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) was used to detect peroxyl, alkoxyl and carbon-centred radicals produced by reaction of t-butyl hydroperoxide (tBuOOH) with rat liver microsomal fraction. The similarity of the hyperfine coupling constants of the peroxyl and alkoxyl radical adducts to those obtained previously with isolated enzymes suggests that these species are the tBuOO. and tBuO. adducts. The effects of metal-ion chelators, heat denaturation, enzyme inhibitors and reducing equivalents demonstrate that these species arise from reaction of tBuOOH with a haem enzyme such as cytochrome P-450 or cytochrome b5. In the absence of NADPH or NADH the previously undetected peroxyl radical adduct is the major species observed. In the presence of these reducing equivalents the alkoxyl and carbon-centred radical adducts predominate, which is in accord with product studies on similar systems. These results demonstrate that both reductive and oxidative decomposition of tBuOOH can occur in rat liver microsomal fraction with the reductive pathway favoured in the presence of NADH or NADPH. PMID- 2930472 TI - Characteristics of butanol metabolism in alcohol dehydrogenase-deficient deermice. AB - Deermice lacking the low-Km alcohol dehydrogenase eliminated butan-1-ol, a substrate for microsomal oxidation but not for catalase, at 117 mumol/min per kg body wt. Microsomal fractions and hepatocytes metabolized butan-1-ol also (Vmax. = 6.7 nmol/min per nmol of cytochrome P-450, Km = 0.85 mM; Vmax. = 5.3 nmol/min per 10(6) cells, Km = 0.71 mM respectively). These results are consistent with alcohol oxidation by the microsomal system in these deermice. PMID- 2930473 TI - Interferences with assay of creatine kinase activity in vitro. PMID- 2930474 TI - Use of inhibitors in studies of the processes of cytosolic enzyme release from skeletal muscle. PMID- 2930475 TI - Extremely rapid endocytosis mediated by the mannose receptor of sinusoidal endothelial rat liver cells. AB - Isolated sinusoidal endothelial rat liver cells (EC) in suspension bound and internalized ovalbumin, a mannose-terminated glycoprotein, in a saturable manner. The binding and uptake were Ca2+-dependent and were effectively inhibited by alpha-methyl mannoside and yeast mannan, but not by galactose or asialoglycoproteins. This corresponds to the binding specificity described for the mannose receptor of macrophages and non-parenchymal liver cells. Binding studies indicated a surface pool of 20,000-25,000 mannose receptors per cell, with a dissociation constant of 6 x 10(-8) M. Uptake and degradation of ovalbumin by isolated EC were inhibited by weak bases and ionophores which inhibit acidification of endocytic vesicles and dissociation of receptor-ligand complexes. Cycloheximide had no effect on uptake or degradation. Degradation, but not uptake, was inhibited by leupeptin. We conclude that ovalbumin dissociates from the mannose receptors in the endosomal compartment and the receptors are recycled to the cell surface, while the ovalbumin is directed to the lysosomes for degradation. A fraction of the internalized ovalbumin was recycled intact to the cell surface and escaped degradation (retroendocytosis). The rate of internalization of ovalbumin by isolated EC was very fast, with a Ke (endocytotic rate constant) of 4.12 min-1, which corresponds to a half-life of 10 s for the surface pool of receptor-ligand complexes. To our knowledge, this is the highest Ke reported for a receptor-mediated endocytosis system. PMID- 2930476 TI - Preparation and characterization of dog pancreas microsomal membranes specifically depleted of protein disulphide-isomerase. AB - 1. The selective release of protein disulphide-isomerase from dog pancreas and rat liver microsomal membranes was studied to throw light on the mechanisms of retention of this enzyme within the endoplasmic reticulum, and in order to prepare microsomal membranes specifically depleted of the enzyme. 2. Protein disulphide-isomerase was quantitatively released from dog pancreas microsomal membranes by washing at pH 9 and above, as demonstrated both by enzyme assay and by immunoblotting analysis. 3. Integral membrane proteins implicated in the process of translocation and segregation of secretory proteins were retained in pH 9-washed dog pancreas microsomal membranes. 4. After pH 9 washing, dog pancreas microsomal membranes were fully active in the translocation, segregation and processing of nascent secretory proteins; these membranes therefore provide a useful experimental system for testing the action of protein disulphide-isomerase on nascent secretory proteins. 5. Protein disulphide-isomerase was not released from rat liver microsomal membranes by pH 9 washing, and was much less readily released from these membranes by sonication, washing etc. than from dog pancreas microsomal membranes. 6. The mechanism of retention of protein disulphide isomerase, and of other resident proteins of the lumen of the endoplasmic reticulum, is discussed in the light of these findings. PMID- 2930478 TI - Beta-adrenergic induction of a cysteine-proteinase-inhibitor mRNA in rat salivary glands. AB - Transcripts encoding the cysteine-proteinase inhibitor rat cystatin S are induced in submandibular and parotid glands by the beta-adrenergic agonist isoproterenol (isoprenaline). High levels of cystatin S mRNA persist in glands of chronically treated animals for 6 days after discontinuation of the catecholamine, indicating a long half-life of the mRNA. Post-transcriptionally the size of the mRNA decreases, owing to a shortening of the poly(A) tail. PMID- 2930477 TI - Sequential changes in the expression of mitochondrial protein mRNA during the development of brown adipose tissue in bovine and ovine species. Sudden occurrence of uncoupling protein mRNA during embryogenesis and its disappearance after birth. AB - Samples of adipose tissue were obtained from different sites in bovine and ovine foetuses and newborns. RNA was isolated and analysed using bovine cDNA and ovine genomic probe for uncoupling protein (UCP), cDNA for subunits III and IV of cytochrome c oxidase and cDNA for ADP/ATP carrier. UCP mRNA was characterized for the first time in foetal bovine and ovine adipose tissue. It appeared later than mRNA of cytochrome c oxidase subunit III, and increased dramatically at birth (10 fold). ADP/ATP carrier mRNA was expressed at a lower level but also increased 10 fold at birth. It was demonstrated that UCP mRNA reached its highest level at birth in all bovine adipose tissues studied, except subcutaneous tissue. It disappeared quickly afterwards, being no longer detectable two days after birth. Similar variations were observed in newborn lambs. ADP/ATP carrier mRNA showed the same pattern of expression as UCP mRNA; although it was still lightly expressed two days after birth, it disappeared soon afterwards. Only mRNAs for cytochrome c oxidase subunits III and IV remained at the same level during the first postnatal week. On the basis of these data and of observations reported in the literature a sequence of events for the development of brown adipose cells in vivo is proposed. Soon after birth the perirenal adipose tissue of ruminants, which still contains mitochondria of typical brown adipose tissue morphology and high levels of cytochrome c oxidase mRNA, lacks UCP mRNA. Can it still be considered as brown fat? Ruminant species appear to be attractive models to study both the differentiation of brown adipose tissue and its possible conversion to white fat in large animals. PMID- 2930480 TI - [Leu]enkephalin stimulates carbohydrate metabolism in isolated hepatocytes and kidney tubule fragments by interaction with angiotensin II receptors. AB - The possibility that the effects of [Leu]enkephalin in vitro on hepatic carbohydrate metabolism are mediated by interaction with angiotensin II receptors has been examined. Preincubation of hepatocytes with either the angiotensin II receptor antagonist [Sar1,Ile8]angiotensin II or 10 mM-dithiothreitol abolished the ability of both angiotensin II and [Leu]enkephalin to increase phosphorylase a in hepatocytes prepared from fed rats. Dithiothreitol had no effect on the stimulation of phosphorylase in the presence of glucagon or phenylephrine, although it also inhibited the response to vasopressin. [Leu]enkephalin displaced specifically bound 125I-labelled angiotensin II from hepatic plasma membranes over a concentration range of 10(-7)-10(-5) M. This correlated with the dose response required to stimulate phosphorylase activity in intact hepatocytes and suggests that the effects of the opioid peptides on carbohydrate metabolism in liver are the result of cross-reactivity of the peptides with angiotensin II receptors. Addition of 10(-5) M-[Leu]enkephalin to isolated kidney tubule fragments stimulated gluconeogenesis from 5 mM-pyruvate, the magnitude of stimulation being comparable to that by either angiotensin II or adrenaline. This effect of the opioid peptide was also abolished by pretreatment of the tubules with [Sar1,Ile8]angiotensin II, suggesting that the ability of [Leu]enkephalin to interact with angiotensin II receptors is not restricted to the liver, but may occur in other tissues where both receptors occur together. PMID- 2930479 TI - Processing of cholesteryl ester from low-density lipoproteins in the rat. Hepatic metabolism and biliary secretion after uptake by different hepatic cell types. AB - Biliary secretion of the cholesteryl ester moiety of (modified) low-density lipoprotein (LDL) was examined under various experimental conditions in the rat. Human LDL or acetylated LDL (acetyl-LDL), radiolabelled with [3H]cholesteryl oleate, was administered intravenously to unanesthetized rats equipped with permanent catheters in the bile duct, duodenum and heart. LDL was cleared relatively slowly from plasma, mainly by Kupffer cells. At 3 h after injection, only 0.9% of the radioactivity was found in bile; after 12 h this value was 4.5%. Uptake of LDL by hepatocytes was stimulated by treatment of the rats with 17 alpha-ethinyloestradiol (EE; 5 mg/kg for 3 successive days); this resulted in a more rapid secretion of radioactivity into bile, 3.9% and 12.4% after 3 h and 12 h respectively. The extremely rapid uptake of acetyl-LDL via the scavenger pathway, mainly by endothelial cells, resulted in the secretion of only 2.1% of its 3H label into bile within 3 h, and 9.5% within 12 h. Radioactivity in bile was predominantly in the form of bile acids; only a small part was secreted as free cholesterol. However, the specific radioactivity of biliary cholesterol was higher than that of bile acids in all three experimental conditions. EE-treated animals did not form cholic acid from [3H]cholesteryl oleate, which was a major product of the cholesteryl oleate from LDL and acetyl-LDL in untreated rats, but formed predominantly very polar bile acids, i.e. muricholic acids. It is concluded that uptake of human LDL or acetyl-LDL by the liver of untreated rats is not efficiently coupled to biliary secretion of cholesterol (bile acids). This might be due to the anatomical localization of their principal uptake sites, the Kupffer cells and the endothelial cells respectively. Induction of LDL uptake by hepatocytes by EE treatment warrants a more efficient disposition of cholesterol from the body via bile. PMID- 2930481 TI - Effect of the binding of bilirubin to either the first class or the second class of binding sites of the human serum albumin molecule on its photochemical reaction. AB - The kinetics of the photochemical changes of bilirubin were studied at a constant concentration of bilirubin bound either to the first class or to the second class of binding sites of the human serum albumin molecule. The more the bilirubin binds to the first class of binding sites in the human serum albumin molecule, the more readily geometric photoequilibrium to give (ZE)-bilirubin takes place. The more the bilirubin binds to the second class of binding sites or allosterically transformed binding sites induced by added SDS, the more readily structural photoisomerization, i.e. the formation of (EZ)-cyclobilirubin, takes place. When the serum bilirubin concentration is at low, safe, values bilirubin binds exclusively to the first class of binding sites and serves as an antioxidant [Onishi, Yamakawa & Ogawa (1971) Perinatology 1, 373-379]; at these concentrations human serum albumin protects bilirubin from irreversible photodegradation by only allowing readily reversible geometric photoisomerization. As the serum bilirubin concentration increases to high, and potentially dangerous, values, bilirubin binds to the second class of binding sites, and under these conditions human serum albumin seems to promote the photocyclization of bilirubin. During irradiation human serum albumin seems to act by retaining low, useful, concentrations of bilirubin while facilitating irreversible photoisomerization of excess bilirubin. PMID- 2930482 TI - Effect of alpha-sarcin and ribosome-inactivating proteins on the interaction of elongation factors with ribosomes. AB - alpha-Sarcin from Aspergillus giganteus and the ribosome-inactivating proteins (RIPs) from higher plants inactivate the 60 S ribosomal subunit. The former is an RNAase, whereas RIPs are N-glycosidases. The site of cleavage of RNA and that of N-glycosidic depurinization are at one nucleotide distance in 28 S rRNA [Endo & Tsurugi (1987) J. Biol. Chem. 262, 8128-8130]. The effect of alpha-sarcin and that of RIPs on the interaction of elongation factors with Artemia salina (brine shrimp) ribosomes have been investigated. alpha-Sarcin inhibits both the EF1 (elongation factor 1)-dependent binding of aminoacyl-tRNA and the GTP-dependent binding of EF2 (elongation factor 2) to ribosomes, whereas two of the RIPs tested, ricin from Ricinus communis (castor bean) and volkensin from Adenia volkensii (kilyambiti), inhibit only the latter reaction. EF2 protects ribosomes from inactivation by both alpha-sarcin and ricin. The EF1-binding site is affected only by alpha-sarcin. The sensitivity of this site to alpha-sarcin is increased by pretreatment of ribosomes with ricin. A. salina ribosomes were highly resistant to the third RIP tested, namely gelonin from Gelonium multiflorum. All four proteins tested have, however, a comparable activity on the rabbit reticulocyte-lysate system. PMID- 2930483 TI - Characterization of a proteinase inhibitor isolated from the fungal pathogen Coccidioides immitis. AB - A proteinase inhibitor was isolated from the cytosol and cell wall of the fungal respiratory pathogen Coccidioides immitis. The inhibitor was purified to apparent homogeneity by acid precipitation, gel filtration and reverse-phase h.p.l.c. It has an Mr of about 5000 under reducing conditions, as revealed by SDS/polyacrylamide-gel electrophoresis, and is both heat-stable and tolerant to low pH. The inhibitor can efficiently block activity of a 36,000-Mr serine proteinase previously isolated from the same cell-wall fraction of C. immitis, and the two molecules react in a 1:1 stoichiometry. The dissociation constant (Ki) of the enzyme-inhibitor complex is 2.3 x 10(-8) M. We suggest that the low Mr inhibitor may play a role in regulation of the activity of the cell-wall associated 36,000-Mr proteinase during sporulation of C. immitis. PMID- 2930484 TI - Cellular location of the cleavage event of the polymeric immunoglobulin receptor and fate of its anchoring domain in the rat hepatocyte. AB - Transcytosis of polymeric immunoglobulin (pIg) across glandular and mucosal epithelia is mediated by a member of the immunoglobulin supergene family, the pIg receptor. During transcellular routing, the receptor is cleaved and its ectoplasmic domain, known as secretory component (SC), is released into secretions bound to pIg. Using receptor-domain-specific antibodies, we have combined cell fractionation and immunoblotting of rat liver to examine the cellular routing of the receptor, the cellular location of the cleavage event and the fate of the anchor domain. Cleavage is a late event in receptor processing. It appears to occur at the canalicular plasma membrane, since intact receptor is present in this membrane domain and no SC is detected in whole liver homogenate or in cell fractions. The membrane anchor remaining after cleavage can be recovered in bile, as well as in a low-density fraction obtained after equilibrium centrifugation of liver (microsomal fractions) on sucrose density gradients. These data suggest that the membrane-anchor domain may be internalized as well as secreted together with SC into bile. PMID- 2930485 TI - Regulation of polyamine biosynthesis in rat hepatoma (HTC) cells by a bisbenzyl polyamine analogue. AB - A bisbenzyl polyamine analogue, MDL 27695, rapidly repressed ornithine decarboxylase (ODC) and S-adenosyl-L-methionine decarboxylase (AdoMet DC) activity and depleted polyamines in rat hepatoma (HTC) cells. The suppression of ODC and AdoMet DC activity was temporally related to metabolism of MDL 27695 by intracellular polyamine oxidase to a free-amine analogue, MDL 26752, which, when added directly to HTC cells, suppressed ODC activity and polyamine biosynthesis more rapidly and to a greater extent than did the bisbenzyl analogue. The ODC suppression caused by MDL 27695 was completely blocked by the addition of a polyamine oxidase inhibitor to the HTC-cell cultures along with MDL 27695. These data suggested that MDL 27695 acted as a prodrug, with metabolism to an active analogue being necessary for ODC repression to occur. MDL 27695 and MDL 26752 completely abolished division of HTC cells when added to cultures at 1 microM. This established them as being among the most potent antiproliferative polyamine analogues yet described. MDL 27695 has also been shown to possess significant antimalarial effects both in vitro and in vivo, and it is possible that the marked suppression of polyamine biosynthesis described herein may contribute to its anti-malarial effects as well as its antiproliferative effects in mammalian cells. PMID- 2930486 TI - The occurrence of disulphide bonds in purified clathrin light chains. AB - Three forms of clathrin light chain contain two cysteine residues. These are the predominant brain-specific forms of LCa and LCb and the non-brain form of LCb. After purification in the absence of thiols they contain intramolecular disulphide bonds. The reduced and the oxidized forms show differences in electrophoretic mobility, explaining the variable and heterogeneous patterns observed on electrophoresis. Accessibility of the thiol groups in the free light chains is greater than when they are associated with the heavy chain. In contrast the cysteine residues of the clathrin heavy chain are completely inaccessible in the absence of denaturants and are not found in disulphide bonds. The antigenic properties of the oxidized and the reduced forms of the clathrin light chains are similar, as is their capacity to bind to the clathrin heavy chain. After isolation in the presence of 10 mM-iodoacetamide, the light-chain cysteine residues are fully alkylated. The results are consistent with the reduced form being the native state and the light-chain disulphide bonds an artifact of isolation. PMID- 2930487 TI - Ribosome-inactivating proteins from plant cells in culture. AB - 1. Ribosome-inactivating proteins were found in high amounts in one line of cells of Phytolacca americana (pokeweed) cultured in vitro and, in less quantity, in lines of Saponaria officinalis (soapwort) and of Zea mays (corn) cells. 2. The main ribosome-inactivating protein from pokeweed cells was purified to homogeneity. It is a protein with Mr 29,000 and basic pI, similar to the 'pokeweed antiviral protein' (PAP), a ribosome-inactivating protein from pokeweed leaves. We propose to call the pokeweed antiviral protein isolated from pokeweed cells PAP-C. 3. PAP-C inactivates ribosomes in a less-than-equimolar ratio, thus inhibiting protein synthesis by a rabbit reticulocyte lysate with an IC50 (concentration causing 50% inhibition) of 0.067 nM (2 ng/ml), and modifies rRNA in a manner apparently identical to that of ricin and other ribosome-inactivating proteins. It inhibits protein synthesis by intact cells with an IC50 of 0.7-3.4 microM, and is toxic to mice with an LD50 of 0.95 mg/kg. PMID- 2930488 TI - The purification of a 50 kDa protein-actin complex from unfertilized sea-urchin (Strongylocentrotus purpuratus) eggs. AB - The 100,000 g supernatant from the unfertilized egg of the sea urchin Strongylocentrotus purpuratus has been fractionated on DEAE-cellulose and analysed for Ca2+-binding activity by the Chelex-100 competitive Ca2+-binding activity assay. The major peak of Ca2+-binding activity was subjected to further purification and the Ca2+-binding protein responsible for this Ca2+-binding activity peak has been isolated and characterized. Non-denaturing polyacrylamide gel electrophoresis (PAGE) followed by 45Ca2+ autoradiography suggested a molecular mass of 80 kDa for the Ca2+-binding protein. SDS/PAGE revealed that the 80 kDa protein consisted of a 1:1 molar complex of proteins of 50 and 42 kDa. The 42 kDa protein was identified as actin. The complex was not dissociated by extensive dialysis against an EGTA-containing buffer. The EGTA-stable complex was named '50K-A'. PMID- 2930489 TI - The 50 kDa protein-actin complex from unfertilized sea-urchin (Strongylocentrotus purpuratus) eggs. Interaction with actin. AB - In the preceding paper [Golsteyn & Waisman (1989) Biochem. J. 257, 809-815] an EGTA-stable, Ca2+-binding heterodimer comprised of a 50 kDa protein and actin called '50K-A' was identified in the unfertilized eggs of the sea urchin Strongylocentrotus purpuratus. In the present paper we have documented the binding of 50K-A to DNAase I and the effect of 50K-A on the kinetics of actin polymerization. When 50K-A was added to pyrene-labelled rabbit skeletal-muscle actin and the salt concentration increased, the initial rate of actin polymerization was inhibited by a very low molar ratio of 50K-A to actin. Furthermore, the steady-state level of G-actin was increased in the presence of 50K-A, suggesting that 50K-A caps the preferred end of actin polymer, shifting the steady-state concentration to that of the non-preferred end. Dilution of F actin to below its critical concentration into 50K-A resulted in a much slower rate of depolymerization, consistent with capping of the preferred end. In contrast with the Ca2+-dependent binding to DNAase, the effect of 50K-A on the kinetics of actin assembly and disassembly was Ca2+-independent. These results suggest that 50K-A is a novel actin-binding protein with some similarities to the severin/fragmin/gelsolin family of F-actin-capping proteins. PMID- 2930490 TI - Ca2+-calmodulin binding to caldesmon and the caldesmon-actin-tropomyosin complex. Its role in Ca2+ regulation of the activity of synthetic smooth-muscle thin filaments. AB - We measured the concentration of calmodulin required to reverse inhibition by caldesmon of actin-activated myosin MgATPase activity, in a model smooth-muscle thin-filament system, reconstituted in vitro from purified vascular smooth-muscle actin, tropomyosin and caldesmon. At 37 degrees C in buffer containing 120 mM KCl, 4 microM-Ca2+-calmodulin produced a half-maximal reversal of caldesmon inhibition, but more than 300 microM-Ca2+-calmodulin was necessary at 25 degrees C in buffer containing 60 mM-KCl. The binding affinity (K) of caldesmon for Ca2+ calmodulin was measured by a fluorescence-polarization method: K = 2.7 x 10(6) M 1 at 25 degrees C (60 mM-KCl); K = 1.4 x 10(6) M-1 at 37 degrees C in 70 mM-KCl containing buffer; K = 0.35 x 10(6) M-1 at 37 degrees C in 120 mM-KCl- containing buffer (pH 7.0). At 37 degrees C/120 mM-KCl, but not at 25 degrees C/60 mM-KCl, Ca2+-calmodulin bound to caldesmon bound to actin-tropomyosin (K = 2.9 x 10(6) M 1). Ca2+ regulation in this system does not depend on a simple competition between Ca2+-calmodulin and actin for binding to caldesmon. Under conditions (37 degrees C/120 mM-KCl) where physiologically realistic concentrations of calmodulin can Ca2+-regulate synthetic thin filaments, Ca2+-calmodulin reverses caldesmon inhibition of actomyosin ATPase by forming a non-inhibited complex of Ca2+-calmodulin-caldesmon-(actin-tropomyosin). PMID- 2930491 TI - Endocytosis of hyaluronic acid by rat liver endothelial cells. Evidence for receptor recycling. AB - Hyaluronic acid (HA) is cleared from the blood by liver endothelial cells through receptor-mediated endocytosis [Eriksson, Fraser, Laurent, Pertoft & Smedsrod (1983) Exp. Cell Res. 144, 223-238]. We have measured the capacity of cultured rat liver endothelial cells to endocytose and degrade 125I-HA (Mr approximately 44,000) at 37 degrees C. Endocytosis was linear for 3 h and then reached a plateau. The rate of endocytosis was concentration-dependent and reached a maximum of 250 molecules/s per cell. Endocytosis of 125I-HA was inhibited more than 92% by a 150-fold excess of non-radiolabelled HA. HA, chondroitin sulphate and heparin effectively competed for endocytosis of 125I-HA, whereas glucuronic acid, N-acetylglucosamine, DNA, RNA, polygalacturonic acid and dextran did not compete. In the absence of cycloheximide, endothelial cells processed 13 times more 125I-HA in 6 h than their total (cell-surface and intracellular) specific HA binding capacity. This result was not due to degradation and rapid replacement of receptors, because, even in the presence of cycloheximide, these cells processed 6 times more HA than their total receptor content in 6 h. Also, in the presence of cycloheximide, no decrease in 125I-HA-binding capacity was seen in cells processing or not processing HA for 6 h, indicating that receptors are not degraded after the endocytosis of HA. During endocytosis of HA at 37 degrees C, at least 65% of the intracellular HA receptors became occupied with HA within 30 min. This indicates that the intracellular HA receptors (75% of the total) function during continuous endocytosis. Hyperosmolarity inhibits endocytosis and receptor recycling in the asialoglycoprotein and low-density-lipoprotein receptor systems by disrupting the coated-pit pathway [Heuser & Anderson (1987) J. Cell Biol. 105, 230a; Oka & Weigel (1988) J. Cell. Biochem. 36, 169-183]. Hyperosmolarity inhibited 125I-HA endocytosis in liver endothelial cells by more than 90%, suggesting use of a coated-pit pathway by this HA receptor. We conclude that liver endothelial cell HA receptors are recycled during the continuous endocytosis and processing of HA. PMID- 2930492 TI - Guanine nucleotides induce tyrosine phosphorylation and activation of the respiratory burst in neutrophils. AB - Activation of the NADPH oxidase was examined in electrically permeabilized human neutrophils exposed to non-hydrolysable guanine nucleotides. Guanosine 5'-[gamma thio]triphosphate (GTP[S]) induced a marked increase in the rate of O2 consumption, which was partially resistant to staurosporine, an inhibitor of protein kinase C, under conditions where the response to diacylglycerol was virtually abolished. The respiratory burst elicited by GTP[S] was dependent on the presence of ATP and Mg2+, suggesting involvement of phosphorylation reactions. Accordingly, phosphoprotein formation was greatly stimulated by the guanine nucleotide. The polypeptide phosphorylation pattern induced by GTP[S] was similar to, but not identical with, that observed with diacylglycerol, indicating the activation of kinases other than protein kinase C by the guanine nucleotide. The possible involvement of tyrosine kinases was assessed by immunoblotting using anti-phosphotyrosine antibodies. Treatment of electroporated cells with GTP[S] stimulated the accumulation of tyrosine-phosphorylated proteins. This effect was not induced by diacylglycerol, indicating that tyrosine phosphorylation is not secondary to stimulation of protein kinase C. The results indicate that, in neutrophils, activated G-proteins can stimulate tyrosine kinase and/or inhibit tyrosine phosphatase activity. Changes in the amounts of tyrosine-phosphorylated proteins may signal activation of the respiratory burst. PMID- 2930493 TI - Dendrotoxin acceptor from bovine synaptic plasma membranes. Binding properties, purification and subunit composition of a putative constituent of certain voltage activated K+ channels. AB - Dendrotoxin is a snake polypeptide that blocks selectively and potently certain voltage-sensitive, fast-activating K+ channels in the nervous system, where it binds with high affinity to membranous acceptors. Herein, the acceptor protein for dendrotoxin in bovine synaptic membranes is solubilized in active form and its complete purification achieved by affinity chromatography, involving a novel elution procedure. This putative K+-channel constituent is shown to be a large oligomeric glycoprotein containing two major subunits, with Mr values of 75,000 and 37,000. PMID- 2930494 TI - Differences in phorbol-ester-induced down-regulation of protein kinase C between cell lines. AB - Down-regulation of protein kinase C induced by 12-O-tetradecanoylphorbol 13 acetate (TPA) was examined in Swiss 3T3, V79, MDBK and C6 cells by Western blotting. Variations in the rate of down-regulation caused by treatment with 100 nM-TPA were observed; TPA treatment for 5 h caused maximal down-regulation in V79 cells, whereas TPA treatment for 10 h or 30 h was needed for maximal down regulation of protein kinase C in MDBK or Swiss 3T3 cells respectively. The decrease in amount of immunologically detectable protein kinase C was 30% in MDBK cells and 100% in V79 and Swiss 3T3 cells. MDBK and C6 cells could be completely depleted of protein kinase C by treatment with 250 nM-TPA. In C6 cells, after treatment with 500 nM-TPA, an 80% loss of protein kinase C was seen over 10 h. Measurement of the numbers of phorbol-ester-binding sites remaining in each cell line when protein kinase C was maximally down-regulated indicated that in MDBK and Swiss 3T3 cells loss of phorbol-ester-binding sites paralleled loss of protein kinase C, whereas in V79 and C6 cells no such correlation was observed. PMID- 2930496 TI - Adipsin mRNA amounts are not decreased in the genetically obese Zucker rat. AB - Adipsin gene expression as assessed by mRNA amounts was examined in adipose tissue of genetically obese rats at the onset (16 days of age) or at later stages (30 and 60 days of age) of obesity. Amounts of mRNA were equivalent in obese and lean rats at 16 days of age. In adult rats, we observed a 2-fold decrease in adipsin mRNA in the obese rats compared with control lean rats, which was abolished by weaning the animals on a high-fat diet. Our data show that, in sharp contrast with genetically obese mice, adipsin mRNA is not suppressed in genetically obese Zucker rats. PMID- 2930495 TI - Pyruvate carboxylation in the rat heart. Role of biotin-dependent enzymes. AB - Pyruvate carboxylation in the isolated perfused rat heart was studied under steady-state conditions. A biotin deficiency resulting in a 90% decrease in myocardial pyruvate carboxylase left the pyruvate carboxylation rate unchanged. Pyruvate carboxylation in heart muscle must therefore take place by means of an enzyme which does not contain biotin. The kinetic properties and mass-action ratio of the NADP-linked malic enzyme in heart muscle can be taken as circumstantial evidence in favour of the role of malic enzyme in pyruvate carboxylation in myocardium. PMID- 2930497 TI - Structure of the human lactate dehydrogenase B gene. AB - Human genomic clones containing parts of the lactate dehydrogenase B (LDH-B) gene (approx. 25 kb in length) were isolated and characterized. The protein-coding sequence of human LDH-B gene is interrupted by six introns at codons nos. 42-43, 82, 140, 198, 237 and 278-279, and the positions of these introns are homologous to those of LDH-A genes from man and mouse. The 5' non-coding region of human LDH B gene is interrupted by an intron six nucleotide residues upstream of the ATG translation-initiation site, whereas those of human and mouse LDH-A genes are interrupted at 24 nucleotide residues 5' to the ATG initiation codon. As is the case of LDH-A genes from man and mouse, there is no intron in the 3' non-coding region of human LDH-B gene. PMID- 2930499 TI - Numbering of atoms in myo-inositol. Recommendations 1988. Nomenclature Committee of the International Union of Biochemistry. AB - A relaxation of previous recommendations on the numbering of the atoms of myo inositol is suggested, so that substituents are not necessarily numbered so that the smallest possible locant is used. This allows an alternative designation to be used, when authors wish, to bring out structural relationships. PMID- 2930498 TI - Feedback regulation of S-adenosylmethionine decarboxylase synthesis. AB - Treatment of Ehrlich ascites-tumour cells with 1-amino-oxy-3-aminopropane (AOAP), a potent inhibitor of ornithine decarboxylase, resulted in a marked decrease in cellular contents of putrescine and spermidine, concomitant with an arrest of cell growth. The activity of S-adenosylmethionine decarboxylase (AdoMetDC) was greatly increased in cells treated with AOAP. This increase in AdoMetDC activity was shown to be, at least partly, caused by enhanced synthesis of the enzyme, which most likely was induced by the change in cellular polyamine content. PMID- 2930500 TI - Purification of the neutral proteoglycan-degrading metalloproteinase from human articular cartilage tissue and its identification as stromelysin matrix metalloproteinase-3. AB - The 'neutral' proteoglycan-degrading metalloproteinase of human articular cartilage was purified 3,500-fold by use of an anti-(matrix metalloproteinase-3) immunoglobulin G affinity column. Molecular masses of the latent and multiple active forms and specificity of action on casein, transferrin, gelatin and fibronectin were identical with those of authentic stromelysin (matrix metalloproteinase-3) from cultured human rheumatoid synovial fibroblasts. The optimum pH of this proteinase on proteoglycan monomer was pH 5.5, and on Azocoll, 6.2; digestion of fibronectin and gelatin was more extensive at pH 5.5 than at 7.5. PMID- 2930502 TI - Presence of insulin receptors in cultured glial C6 cells. Regulation by butyrate. AB - The presence of insulin receptor and its regulation by butyrate and other short chain fatty acids was studied in C6 cells, a rat glioma cell line. Intact C6 cells bind 125I-insulin in a rapid, reversible and specific manner. Scatchard analysis of the binding data gives typical curvilinear plots with apparent affinities of approx. 6 nM and 70 nM for the low-affinity (approx. 90% of total) and high-affinity (approx. 10% of total) sites respectively. Incubation with butyrate results in a time- and dose-dependent decrease of insulin binding to C6 cells. A maximal effect was found with 2 mM-butyrate that decreased the receptor by 40-70% after 48 h. Butyrate decreased numbers of receptors of both classes, but did not significantly alter receptor affinity. Other short-chain fatty acids, as well as keto acids, had a similar effect, but with a lower potency. Cycloheximide caused an accumulation of insulin receptors at the cell surface, since insulin binding increased and receptor affinity did not change after incubation with the inhibitor. Simultaneous addition of butyrate and cycloheximide abolished the loss of receptors produced by the fatty acid. In cells preincubated with butyrate, cycloheximide also produced a large increase in receptor numbers, showing that in the absence of new receptor synthesis a large pool of receptors re-appears at the surface of butyrate-treated cells. PMID- 2930501 TI - Quantitative analysis of intermediary metabolism in rat hepatocytes incubated in the presence and absence of ethanol with a substrate mixture including ketoleucine. AB - Hepatocytes isolated from livers of fed rats were incubated with a mixture of glucose (10 mM), ribose (1.0 mM), acetate (1.25 mM), alanine (3.5 mM), glutamate (2.0 mM), aspartate (2.0 mM), 4-methyl-2-oxovaleric acid (ketoleucine) (3.0 mM), and, in paired flasks, 10 mM-ethanol. One substrate was 14C-radiolabelled in any given incubation. Incorporation of 14C into glucose, glycogen, CO2, lactate, alanine, aspartate, glutamate, acetate, urea, lipid glycerol, fatty acids and the 1- and 2,3,4-positions of ketone bodies was measured after 20 and 40 min of incubation under quasi-steady-state conditions. Data were analysed with the aid of a realistic structural metabolic model. In each of the four conditions examined, there were approx. 77 label incorporation measurements and several measurements of changes in metabolite concentrations. The considerable excess of measurements over the 37 independent flux parameters allowed for a stringent test of the model. A satisfactory fit to these data was obtained for each condition. There were large bidirectional fluxes along the gluconeogenic/glycolytic pathways, with net gluconeogenesis. Rates of ureagenesis, oxygen consumption and ketogenesis were high under all four conditions studied. Oxygen utilization was accurately predicted by three of the four models. There was complete equilibration between mitochondrial and cytosolic pools of acetate and of CO2, but for several of the metabolic conditions, two incompletely equilibrated pools of mitochondrial acetyl-CoA and oxaloacetate were required. Ketoleucine was utilized at a rate comparable to that reported by others in perfused liver and entered the mitochondrial pool of acetyl-CoA directly associated with ketone body formation. Ethanol, which was metabolized at rates comparable to those in vivo, caused relatively few changes in overall flux patterns. Several effects related to the increased NADH/NAD+ ratio were observed. Pyruvate dehydrogenase was completely inhibited and the ratio of acetoacetate to 3-hydroxybutyrate was decreased; flux through glutamate dehydrogenase, the citric acid cycle, and ketoleucine dehydrogenase were, however, only slightly inhibited. Net production of ATP occurred in all conditions studied and was increased by ethanol. Futile cycling was quantified at the glucose/glucose 6-phosphate, glycogen/glucose 6 phosphate, fructose 6-phosphate/fructose 1,6-bis-phosphate, and phosphoenolpyruvate/pyruvate/oxaloacetate substrate cycles. Cycling at these four loci consumed about 22% of cellular ATP production in control hepatocytes and 14% in ethanol-treated cells. PMID- 2930503 TI - Retrograde intrabiliary injection of amphipathic materials causes phospholipid secretion into bile. Taurocholate causes phosphatidylcholine secretion, 3-[(3 cholamidopropyl)dimethylammonio]-propane-1-sulphonate (CHAPS) causes mixed phospholipid secretion. AB - The control of biliary phospholipid and cholesterol secretions by bile acid was studied by using the technique of retrograde intrabiliary injection. Taurocholate (TC), a moderately hydrophobic bile acid, taurodehydrocholate (TDHC), a hydrophilic non-micelle-forming bile acid, and 3-[(3-cholamidopropyl) dimethylammonio]propane-1-sulphonate (CHAPS), a detergent, were individually administered by retrograde intrabiliary injection (RII) into the biliary tree, and bile acids, phospholipids and cholesterol subsequently appearing in the bile were measured. TC (1.3 mumol; 45 microliters) injected retrogradely provoked a 3.5-fold increase in biliary phospholipid output for 40 min, as compared with the saline control. Injection of 2.7 mumol of TC (90 microliters) caused a 7.5-fold increase in phospholipid output, which reached a peak at 12 min after RII, and phospholipid output continued for 40 min. Cholesterol output was also elicited under these conditions, showing both dose-dependency and extended secretion. Injection of 1.8 mumol of TDHC caused very little increase in either biliary phospholipid or cholesterol. Injection of 0.9 mumol of CHAPS (45 microliters) provoked a single substantial peak of phospholipid output in the 3 min bile sample. T.l.c. analysis of the phospholipid extracts of the bile collected after each compound showed, for TC, a single compound which co-migrated with the phosphatidylcholine standard, whereas for CHAPS substantial amounts of other phospholipids were present. PMID- 2930504 TI - Effect of cis-unsaturated fatty acids on aortic protein kinase C activity. AB - Long-chain cis-unsaturated fatty acids could substitute for phosphatidylserine and activate bovine aortic protein kinase C in assays with histone as substrate. The optimal concentration was 24-40 microM for oleic, linoleic and arachidonic acids. With arachidonic acid, the Ka for Ca2+ was 130 microM and kinase activity was maximal at 0.5 mM-Ca2+. Diolein only slightly activated the oleic acid stimulated enzyme at low physiological Ca2+ concentrations (0.1 and 10 microM). Oleic acid also stimulated kinase C activity, determined with a Triton X-100 mixed-micellar assay. Under these conditions, the fatty acid activation was absolutely dependent on the presence of diolein, but a Ca2+ concentration of 0.5 mM was still required for maximum kinase C activity. The effect of fatty acids on protein kinase C activity was also investigated with the platelet protein P47 as a substrate, since the properties of kinase C can be influenced by the choice of substrate. In contrast with the results with histone, fatty acids did not stimulate the phosphorylation of P47 by the aortic protein kinase C. Activation of protein kinase C by fatty acids may allow the selective phosphorylation of substrates, but the physiological significance of fatty acid activation is questionable because of the requirement for high concentrations of Ca2+. PMID- 2930506 TI - The structural basis for neutrophil inactivation of C1 inhibitor. AB - Limited proteolysis of C1 inhibitor (C1-INH) by neutrophil elastase, Pseudomonas elastase and snake venoms resulted in initial cleavage within the molecule's N terminus followed by further cleavage within the molecule's C-terminally placed reactive centre. N-Terminal proteolysis occurred at peptide bonds 14-15, 36-37 and 40-41. This had no effect on either the inhibitory activity or the heat stability of C1-INH. Proteolysis within the reactive centre occurred at peptide bonds 439-440, 440-441, 441-442 and 442-443. Cleavage at any one of these sites inactivated C1-INH and conferred enhanced heat-stability upon a previously heat labile molecule. Released neutrophil proteinases also cleaved and inactivated C1 INH, suggesting that they may physiologically regulate C1-INH during inflammatory episodes. PMID- 2930505 TI - Bombesin and platelet-derived growth factor stimulate formation of inositol phosphates and Ca2+ mobilization in Swiss 3T3 cells by different mechanisms. AB - Highly purified platelet-derived growth factor (PDGF) or recombinant PDGF stimulate DNA synthesis in quiescent Swiss 3T3 cells. The dose-response curves for the natural and recombinant factors were similar, with half-maximal responses at 2-3 ng/ml and maximal responses at approx. 10 ng/ml. Over this dose range, both natural and recombinant PDGF stimulated a pronounced accumulation of [3H]inositol phosphates in cells labelled for 72 h with [3H]inositol. In addition, mitogenic concentrations of PDGF stimulated the release of 45Ca2+ from cells prelabelled with the radioisotope. However, in comparison with the response to the peptide mitogens bombesin and vasopressin, a pronounced lag was evident in both the generation of inositol phosphates and the stimulation of 45Ca2+ efflux in response to PDGF. Furthermore, although the bombesin-stimulated efflux of 45Ca2+ was independent of extracellular Ca2+, the PDGF-stimulated efflux was markedly inhibited by chelation of external Ca2+ by using EGTA. Neither the stimulation of formation of inositol phosphates nor the stimulation of 45Ca2+ efflux in response to PDGF were affected by tumour-promoting phorbol esters such as 12-O-tetradecanoylphorbol 13-acetate (TPA). In contrast, TPA inhibited phosphoinositide hydrolysis and 45Ca2+ efflux stimulated by either bombesin or vasopressin. Furthermore, whereas formation of inositol phosphates in response to both vasopressin and bombesin was increased in cells in which protein kinase C had been down-modulated by prolonged exposure to phorbol esters, the response to PDGF was decreased in these cells. These results suggest that, in Swiss 3T3 cells, PDGF receptors are coupled to phosphoinositidase activation by a mechanism that does not exhibit protein kinase C-mediated negative-feedback control and which appears to be fundamentally different from the coupling mechanism utilized by the receptors for bombesin and vasopressin. PMID- 2930507 TI - Conformational changes in human serum albumin studied by fluorescence and absorption spectroscopy. Distance measurements as a function of pH and fatty acids. AB - pH- and fatty acid-induced conformational changes in human serum albumin were investigated by fluorescence-energy transfer, determining the distance between Trp-214 and bound bilirubin at 25 degrees C. This distance changes significantly with the pH, being 2.52 +/- 0.01 nm at pH 6, 2.31 +/- 0.04 nm at pH 9, 2.13 +/- 0.07 nm at pH 11.0 and 2.77 nm at pH 11.9. The influence of different fatty acids on the distance was also determined. At pH 7.4 medium-chain fatty acids seem to increase this distance, whereas long-chain fatty acids, at low concentrations, decrease the distance between the two chromophores. The contraction of the protein carrying long-chain saturated fatty acids is even more pronounced at pH 9. PMID- 2930509 TI - Purification and molecular properties of malate dehydrogenase from the marine diatom Nitzschia alba. AB - Malate dehydrogenase (EC 1.1.1.37) was purified to homogeneity from the marine diatom Nitzschia alba. The purification steps consisted of (NH4)2SO4 precipitation, ion-exchange chromatography, Blue Sepharose affinity chromatography and gel filtration. A typical procedure provided 685-fold purification with 58% yield. The Mr of the holoenzyme was estimated to be 322,000 by gel filtration and 316,000 by ultracentrifugation. The enzyme migrated as a single polypeptide spot on two-dimensional polyacrylamide-gel electrophoresis with an Mr of 38,500, suggesting that the holoenzyme consists of eight identical subunits. This is the first case where malate dehydrogenase has been shown to be a homo-octamer; malate dehydrogenases from other sources are predominantly homodimers, with two homotetramers reported so far. The amino acid composition of the enzyme was determined and the N-terminal sequence of the subunit polypeptide was found to be Arg-Lys-Val-Ala-Val-Met-Gly-Ala-Ala-Gly-Gly-Ile-Gly-Gln-Pro-Leu Ser-Leu- Leu-Leu - Lys-Leu-Ser-Pro-Gln-Val-Thr-Glu-Leu-Ser-Lys-Tyr-. For the first 21 amino acid residues, near-identical sequences were reported for the enzymes isolated from pig heart, Escherichia coli, yeast and watermelon. Other physicochemical and catalytic properties, such as sedimentation coefficient, partial specific volume, Stokes radius, excitation and emission maxima, Michaelis constants, pH optima, pH stability range and activation energy, of this enzyme are also presented. PMID- 2930508 TI - Monoclonal antibodies to the membrane domain of the human erythrocyte anion transport protein. Localization of the C-terminus of the protein to the cytoplasmic side of the red cell membrane and distribution of the protein in some human tissues. AB - (1) We have prepared murine monoclonal antibodies to the membrane domain of the human erythrocyte anion transport protein (band 3). (2) All of these antibodies react with regions of the protein located at the cytoplasmic surface of the red cell. (3) One of the antibodies reacts with an epitope present on a cytoplasmic loop of the protein located between the C-terminus and a point 168 amino acids from the C-terminus. The other antibodies recognize different epitopes on the C terminal tail of the protein and the sequences likely to be involved in these epitopes are defined. (4) Our results show that the C-terminus of the red-cell anion transport protein is located on the cytoplasmic side of the red-cell membrane. (5) None of the antibodies inhibited sulphate exchange transport when introduced into resealed red-cell membranes; however, the bivalent form of one of the antibodies reduced the inhibitory potency of 4-acetamido-4' isothiocyanatostilbene disulphonate on sulphate exchange transport in resealed erythrocyte membranes. (6) Immunostaining of human kidney sections with the antibodies showed strong staining of the basolateral membrane of some but not all of the epithelial cells of distal tubules and the initial connecting segment of collecting tubules. With human liver, only the haematopoeitic cells of fetal liver reacted with all the antibodies. PMID- 2930510 TI - Accumulation of inositol polyphosphate isomers in agonist-stimulated cerebral cortex slices. Comparison with metabolic profiles in cell-free preparations. AB - 1. Basal and carbachol-stimulated accumulations of isomeric [3H]inositol mono-, bis-, tris- and tetrakis-phosphates were examined in rat cerebral-cortex slices labelled with myo-[2-3H]inositol. 2. In control samples the major [3H]inositol phosphates detected were co-eluted on h.p.l.c. with Ins(1)P, Ins(4)P (inositol 1- and 4-monophosphate respectively), Ins(1,4)P2 (inositol 1,4-bisphosphate), Ins(1,4,5)P3 (inositol 1,4,5-tris-phosphate) and Ins(1,3,4,5)P4 (inositol 1,3,4,5 tetrakisphosphate). 3. After stimulation to steady state with carbachol, accumulation of each of these products was markedly increased. 4. Agonist stimulation, however, also evoked much more dramatic increased accumulations of a second [3H]inositol trisphosphate, which was co-eluted on h.p.l.c. with authentic Ins(1,3,4)P3 (inositol 1,3,4-trisphosphate) and of three further [3H]inositol bisphosphates ([3H]InsP2(s]. 5. Examination of the latter by chemical degradation by periodate oxidation and/or h.p.l.c. allowed identification of these as [3H]Ins(1,3)P2, [3H]Ins(3,4)P2 and [3H]Ins(4,5)P2 (inositol 1,3-, 3,4- and 4,5 bisphosphates respectively), which respectively accounted for about 22%, 8% and 3% of total [3H]InsP2 in extracts from stimulated tissue slices. 6. By using a h.p.l.c. method which clearly resolves Ins(1,3,4,5)P4 and Ins(1,3,4,6)P4 (inositol 1,3,4,6-tetrakisphosphate), only the former isomer could be detected in extracts from either control or stimulated tissue slices. Similarly, [3H]inositol pentakis- and hexakis-phosphates were not detectable either in the presence or absence of carbachol under the radiolabelling conditions described. 7. The catabolism of [3H]Ins(1,4,5)P3 and [3H]Ins(1,3,4)P3 by cell-free preparations from cerebral cortex was also studied. 8. In the presence of Mg2+, [3H]Ins(1,4,5)P3 was specifically dephosphorylated via [3H]Ins(1,4)P2 and [3H]Ins(4)P to free [3H]inositol, whereas [3H]Ins(1,3,4)P3 was degraded via [3H]Ins(3,4)P2 and, to a lesser extent, via [3H]Ins(1,3)P2 to D- and/or L [3H]Ins(1)P and [3H]inositol. 9. In the presence of EDTA, hydrolysis of [3H]Ins(1,4,5)P3 was greater than or equal to 95% inhibited, whereas [3H]Ins(1,3,4)P3 was still degraded, but yielded only a single [3H]InsP2 identified as [3H]Ins(1,3)P2. 10. The significance of these observations with cell-free preparations is discussed in relation to the proportions of the separate isomeric [3H]inositol phosphates measured in stimulated tissue slices. PMID- 2930511 TI - Immunochemical detection of different isoenzymes of cytochrome P-450 induced in chick hepatocyte cultures. AB - This study investigated whether the same cytochrome P-450 (P-450) isoenzymes were inducible in cultures of chick-embryo hepatocytes as in the liver of chicken embryos. We purified two isoenzymes of cytochrome P-450 from the livers of 17-day old-chick embryos: one of molecular mass approx. 50 kDa induced in vivo by the phenobarbital-like inducer glutethimide, and the second of approx. 57 kDa induced by 3-methylcholanthrene. Rabbit antiserum against the 50 kDa protein inhibited benzphetamine demethylase activity in hepatic microsomes (microsomal fractions) from glutethimide-treated chick embryo. Antiserum to the 57 kDa protein inhibited ethoxyresorufin de-ethylase activity in hepatic microsomes from methylcholanthrene-treated chick embryo. Cultured chick hepatocytes were treated with chemicals known to induce isoenzymes of P-450 in rodent liver. The induced P 450s were quantified spectrophotometrically and characterized by immunoblotting and enzyme assays. From these studies, chemical inducers were classified into three groups: (i) chemicals that induced a P-450 isoenzyme of 50 kDa and increased benzphetamine demethylase activity: glutethimide, phenobarbital, metyrapone, mephenytoin, ethanol, isopentanol, isobutanol, lindane, lysodren; (ii) chemicals that induced a P-450 isoenzyme of 57 kDa and increased ethoxyresorufin de-ethylase activity: 3-methylcholanthrene and 3,3',4,4' tetrachlorobiphenyl; and (iii) the mono-alpha-substituted 2,3',4,4',5 pentabromobiphenyl, which induced both proteins and both activities. The immunochemical data showed that chick-embryo hepatocytes in culture retain the inducibility of glutethimide- and methylcholanthrene-induced isoenzymes of P-450 that are inducible in the liver of the chicken embryo. PMID- 2930512 TI - Oxidation of uroporphyrinogen by methylcholanthrene-induced cytochrome P-450. Essential role of cytochrome P-450d. AB - We have previously shown that uroporphyrinogen is oxidized to uroporphyrin by microsomes (microsomal fractions) from 3-methylcholanthrene-pretreated chick embryo liver [Sinclair, Lambrecht & Sinclair (1987) Biochem. Biophys. Res. Commun. 146, 1324-1329]. We report here that a specific antibody to chick liver methylcholanthrene-induced cytochrome P-450 (P-450) inhibited both uroporphyrinogen oxidation and ethoxyresorufin O-de-ethylation in chick-embryo liver microsomes. 3-Methylcholanthrene-pretreatment of rats and mice markedly increased uroporphyrinogen oxidation in hepatic microsomes as well as P-450 mediated ethoxyresorufin de-ethylation. In rodent microsomes, uroporphyrinogen oxidation required the addition of NADPH, whereas chick liver microsomes required both NADPH and 3,3',4,4'-tetrachlorobiphenyl. Treatment of rats with methylcholanthrene, hexachlorobenzene and o-aminoazotoluene increased uroporphyrinogen oxidation and P-450d, whereas phenobarbital did not increase either. The contribution of hepatic P-450c and P-450d to uroporphyrinogen oxidation and ethoxyresorufin O-de-ethylation in methylcholanthrene-induced microsomes was assessed by using specific antibodies to P-450c and P-450d. Uroporphyrinogen oxidation by methylcholanthrene-induced rat liver microsomes was inhibited up to 75% by specific antibodies to P-450d, but not by specific antibodies to P-450c. In contrast, ethoxyresorufin de-ethylation was inhibited only 20% by anti-P450d but 70% by anti-P450c. Methylcholanthrene-induced kidney microsomes which contain P-450c but non P-450d did not oxidize uroporphyrinogen. These data indicate that hepatic P-450d catalyses uroporphyrinogen oxidation. We suggest that the P-450d-catalysed oxidation of uroporphyrinogen has a role in the uroporphyria caused by hexachlorobenzene and other compounds. PMID- 2930514 TI - Synthesis of the major oil-body membrane protein in developing rapeseed (Brassica napus) embryos. Integration with storage-lipid and storage-protein synthesis and implications for the mechanism of oil-body formation. AB - The synthesis of the major protein and lipid storage reserves during embryogenesis in oilseed rape (Brassica napus L., cv. Mikado) has been examined by biochemical, immunological and immunocytochemical techniques. The mature seeds contained about 45% (w/w) storage oil and 25% (w/w) protein. There were three major seed protein components, i.e. about 40-50% total protein was cruciferin, 20% was napin and 20% was a 18 kDa hydrophobic polypeptide associated with the proteinaceous membrane surrounding the storage oil bodies. Embryogenesis was divided into four overlapping stages with regard to the synthesis of these storage components: (1) for the first 3 weeks after flowering, little, if any, synthesis of storage components was observed; (2) storage-oil synthesis began at about week 3, and maximal rates were from weeks 4 to 7; (3) synthesis of the soluble storage proteins cruciferin and napin started at week 6 and rates were maximal between weeks 8 and 11; (4) the final stage was the synthesis of the 19 kDa oil-body polypeptide, which started at weeks 8-10 and was at a maximal rate between weeks 10 and 12. The synthesis of the 19 kDa oil-body protein therefore occurred independently of the synthesis of the soluble seed storage proteins. This former synthesis did not occur until shortly before the insertion of the 19 kDa polypeptide into the oil-body membrane. No evidence was found, either from sucrose-density-gradient-centrifugation experiments or from immunogold-labelling studies, for its prior accumulation in the endoplasmic reticulum. Conventional and immunogold-electron-microscopic studies showed that oil bodies were synthesized in the early to middle stages of seed development without a strongly electron-dense membrane. Such a membrane was only found at later stages of seed development, concomitantly with the synthesis of the 19 kDa protein. It is proposed that, in rapeseed embryos, oil bodies are initially formed with no proteinaceous membrane. Such a membrane is formed later in development after insertion by ribosomes of the hydrophobic 19 kDa polypeptide directly into the oil bodies. PMID- 2930513 TI - Effect of the reducing environment on the accumulation of elastin and collagen in cultured smooth-muscle cells. AB - We show here that cultured neonatal-rabbit aortic smooth-muscle cells produce and accumulate significant amounts of insoluble elastin. When grown in the presence of ascorbic acid, the amount of insoluble elastin in these cultures decreases, whereas the accumulation of collagen increases. These changes have been attributed to increased hydroxylation of proline in elastin. The function of ascorbic acid in proline hydroxylation is thought to be that of a reductive cofactor that maintains the proper oxidation state of molecular iron in the enzyme complex. This study shows that both ascorbic and isoascorbic acids act similarly to modify the accumulation of elastin and collagen in culture. On the other hand, cultures grown in the presence of dithiothreitol, a reducing agent previously shown to act as a cofactor for prolyl hydroxylase, do not demonstrate altered elastin accumulation. These studies are consistent with the suggestion that there is a specific role for ascorbic acid in this cellular system that cannot be replaced by other reducing cofactors. PMID- 2930515 TI - Nutritional regulation of hepatic glucose-6-phosphate dehydrogenase. Transient activation of transcription. AB - Hepatic glucose-6-phosphate dehydrogenase (G6PDH; EC 1.1.1.49) is subject to nutritional and hormonal regulation. Previous work has shown that increased amounts of mRNA encoding G6PDH can account for the increase in enzyme activity. The results of this study demonstrate that transcription of the G6PDH gene is transiently elevated after ingestion of a high-carbohydrate diet. However, the increased rate of transcription cannot totally account for the increased G6PDH mRNA. The half-life of the G6PDH mRNA appears to be about 4-5-fold higher during ingestion of a high-carbohydrate diet. Thus increased transcription as well as mRNA stability are each partially responsible for the nutritional regulation of G6PDH mRNA. PMID- 2930516 TI - Vanadate inhibits degradation of short-lived, but not of long-lived, proteins in L-132 human cells. AB - Vanadate, at concentrations higher than 0.04 mM, inhibits the intracellular degradation of short-lived proteins in exponentially growing L-132 human cells. The inhibition is not due to a decrease in viability or in the ATP contents of the cells. Since vanadate decreases proteolysis in cell extracts, the inhibition appears to affect the proteinases which degrade these proteins. Under optimal nutritional conditions, the degradation of long-lived proteins is accelerated by vanadate, thus providing additional evidence that in exponentially growing cultured cells degradation of short- and long-lived proteins occurs by different processes. Vanadate also efficiently inhibits the lysosomal degradation of endocytosed proteins and of long-lived proteins under step-down conditions. However, this effect seems to be unrelated to the observed inhibition of degradation of short-lived proteins, because chloroquine and leupeptin, which inhibit degradation of proteins by lysosomes, do not modify the degradation of these proteins. Our results provide for the first time a probe which, owing to its opposite effects on the degradation of short- and long-lived proteins, could be useful to clarify the mechanisms involved in protein degradation in cultured cells. PMID- 2930517 TI - The presence and role of hormone-sensitive lipase in heart muscle. AB - Hormone-sensitive lipase (HSL) catalyses the initial, rate-limiting, reaction in adipose-tissue lipolysis. Hormone-stimulated lipolytic activity has also been observed in the heart, where endogenous triacylglycerol is the major energy store. However, the identity of the intracellular lipase responsible has yet to be established. We have partially purified a neutral lipase from bovine heart muscle and compared its properties with those of HSL from bovine adipose tissue. The heart lipase has the same subunit Mr as HSL, is immunoprecipitated by antiserum raised against purified HSL and is phosphorylated by cyclic AMP dependent protein kinase, apparently at the same site as HSL (as judged by h.p.l.c. of tryptic phosphopeptides). Phosphorylation of the heart lipase was found to result in increased enzyme activity, demonstrating the lipase's potential to respond to hormonal stimuli. The heart lipase was shown to be present in myocytes by its immunoprecipitation from homogenates of rat myocytes by anti-HSL antiserum. These findings are consistent with the conclusion that HSL is responsible for intracellular lipolysis in heart. PMID- 2930518 TI - Human microsomal glutathione S-transferase. Its involvement in the conjugation of hexachlorobuta-1,3-diene with glutathione. AB - A microsomal glutathione S-transferase (GST) was purified from human liver. This enzyme was shown to have characteristics similar to those of the rat microsomal GST described by Morgenstern & De Pierre [(1983) Eur. J. Biochem. 134, 591-597]. The specific activity of human microsomal GST towards 1-chloro-2,4-dinitrobenzene or cumene hydroperoxide can be stimulated by treating the enzyme with N ethylmaleimide. This enhancement of activity is accompanied by increased sensitivity to inhibition by haematin and cholic acid. The subunit Mr values of the rat and human enzymes are similar (approx. 17,300), and the proteins are immunologically related. During purification, both human and rat microsomal GST enzymes are the only hepatic proteins obtained from Triton X-100-solubilized microsomal fractions that show activity towards the nephrotoxin hexachlorobuta 1,3-diene. The involvement of microsomal GST in toxification reactions is discussed. PMID- 2930519 TI - Modulation of phospholipase A2 activity by neutral and anionic glycosphingolipids in monolayers. AB - The effect of neutral (galactocerebroside and asialo-ganglioside GM1) or anionic (sulphatide and gangliosides GM1, GD1a and GT1b) glycosphingolipids on the activity of phospholipase A2 from pig pancreas was studied in mixed monolayers of dilauroyl phosphatidylcholine with the glycosphingolipids in different molar fractions at various constant surface pressures. The activity of the enzyme depends on the proportion and type of glycosphingolipid in the interface. Sulphatide activates the enzyme at all proportions, whereas galactocerebroside shows inhibition or activation depending on its proportion in the film. Asialo ganglioside GM1 and gangliosides GM1, GD1a and GT1b can strongly inhibit the enzyme at relatively low molar fractions in the film in the following order: asialo-ganglioside GM1 less than ganglioside GM1 less than ganglioside GT1b less than ganglioside GD1a. The changes of activity are not due to a direct action of the lipids on the active centre or interfacial recognition region of the enzyme. PMID- 2930520 TI - Macrophage-mediated N-nitrosation of thioproline and proline. AB - Thioproline (Thiazolidine-4-carboxylic acid) and proline were nitrosated by stimulated mouse macrophages in vitro. A macrophage cell line (J774.1, 1.0 x 10(6)/well, 1 ml) was incubated with Escherichia coli lipopolysaccharide, interferon-gamma and thioproline (5 mM) or proline (5 mM). After 72 hr incubation at 37 degrees C, 4 microM N-nitrosothioproline was produced. The amount of N nitrosoproline was much lower than that of N-nitrosothioproline. Thioproline and proline inhibited the formation of carcinogenic N-nitrosomorpholine. N nitrosothioproline and N-nitrosoproline are found as major N-nitroso compounds in human urine. Macrophage mediated N-nitrosation may contribute to the formation of these N-nitrosamino acids in the human body. PMID- 2930521 TI - Caldesmon is present in human and pig erythrocytes. AB - Caldesmon, a major actin- and calcium-dependent calmodulin-binding protein, is now considered as an essential inhibitory factor of the actomyosin machinery in smooth muscle cells as well as in non-muscle cells. Since its structure seems to vary with the cell in a same species and because platelet and erythrocyte have a common embryonic origin, we have used the affinity purified antibody raised against the platelet caldesmon to determine whether this protein is present in erythrocyte. Using the immunoblotting technique, we show here that, in whole erythrocytes, only a single polypeptide crossreacts with this polyclonal antibody. A 71-72 kDa Mr has been calculated from SDS-PAGE. It is therefore different from those of the gizzard (Mr 145-150 kDa) or the platelet (Mr 80 kDa) proteins. Furthermore, we also give evidence that it is not adducin since this newly discovered calcium-dependent calmodulin-binding protein of erythrocyte, does not crossreact with the polyclonal affinity purified antibody raised against platelet caldesmon. PMID- 2930522 TI - N-acetylneuraminic acid and N-glycolylneuraminic acid in glycopeptides of colonic tumor and mucosa in rats treated with carrageenan and 1,2-dimethylhydrazine. AB - N-linked glycopeptides were prepared from colonic tumor (adenocarcinoma) and mucosa in rats treated with carrageenan, an indigestible polysaccharide, and 1,2 dimethylhydrazine. Sialic acids, N-acetylneuraminic acid and N-glycolylneuraminic acid, obtained by acid hydrolysis of the glycopeptides were determined by HPLC. The N-acetylneuraminic acid/N-glycolylneuraminic acid ratio in colonic tumor was 25.2, while each treated mucosa had the values between 0.29 and 0.55. Thus, necessity which observes the qualitative change of sialic acid in malignant transformation was suggested. PMID- 2930523 TI - Streptomyces glucose/xylose isomerase has a single active site for glucose and xylose. AB - A kinetic method which allows one to evaluate whether an enzyme acting on two different substrates has one or two active sites was employed to study the active site of glucose isomerase which catalyses the isomerization of both glucose and xylose. The experimental data on the rates of hydrolysis of mixtures of various concentrations of glucose and xylose by the glucose isomerase from Streptomyces coincides well with the theoretical values calculated for the case of a single active site. PMID- 2930524 TI - The pathways for fluid phase and receptor mediated endocytosis in rat hepatocytes are different but thermodynamically equivalent. AB - In isolated rat hepatocytes fluid phase endocytosis, determined by the uptake of the fluorescent dye lucifer yellow (LY), and receptor mediated endocytosis, determined using a ligand for the asialoglycoprotein receptor (asialo orosomucoid; ASOR), are different pathways based on their different sensitivities to hyperosmolarity induced by sucrose (Oka and Weigel, J. Cell. Biol. 105, 311a, 1987). LY uptake was unaffected by 0.2 M sucrose at all temperatures tested between 12 degrees and 37 degrees C whereas the uptake of 125I-ASOR was completely inhibited at any temperature. Since the two probes are taken up by different pathways it was possible to determine independently the activation energies (Ea) for the fluid phase versus the receptor mediated coated pit endocytic process. The Ea was 26.4 +/- 3.5 and 25.8 +/- 1.9 kcal/mole for, respectively, receptor mediated and fluid phase endocytosis. These values are not significantly different, and we conclude that the fluid phase and receptor mediated pathways are thermodynamically equivalent even though they are independent. PMID- 2930525 TI - Fluorimetric studies of protein kinase C interactions with phospholipids. AB - Dansyl-phosphatidylserine (D-PS) was used as a fluorescence probe to study interactions between protein kinase C (PKC) with phospholipid vesicles. It was found that D-PS fluorescence (520 nm) was enhanced by PKC (excited at 285 nm). The fluorescence energy transfer, indicative of a close association of PKC with D PS vesicles, was differentially modulated by various phospholipids, depending upon their effects on PKC activation state and the manners in which they were present. PKC inhibitors (e.g. polymyxin B and ether lipids) potently inhibited the PKC-enhanced D-PS fluorescence. It is suggested that certain spatial arrangements between PKC and its phospholipid cofactor are essential for the enzyme activation and that D-PS would be a useful probe to study fluorimetrically such interactions. PMID- 2930527 TI - Use of deuterium labelled glucose in evaluating the pathway of hepatic glycogen synthesis. AB - Deuterium labelled glucose has been used to study the pathway of hepatic glycogen synthesis during the fasted-refed transition in rats. Deuterium enrichment of liver glycogen was determined using nuclear magnetic resonance as well as mass spectroscopy. Sixty minutes after oral administration of deuterated glucose to fasted rats, the portal vein blood was fully enriched with deuterated glucose. Despite this, less than half of the glucose molecules incorporated into liver glycogen contained deuterium. The loss of deuterium label from glucose is consistent with hepatic glycogen synthesis by an indirect pathway requiring prior metabolism of glucose. The use of deuterium labelled glucose may prove to be a useful probe to study hepatic glycogen metabolism. Its use may also find application in the study of liver glycogen metabolism in humans by a noninvasive means. PMID- 2930526 TI - 5,6-Dichloro-1-beta-D-ribofuranosylbenzimidazole inhibits a HeLa protein kinase that phosphorylates an RNA polymerase II-derived peptide. AB - A protein kinase that phosphorylates Lys(Tyr-Ser-Pro-Thr-Ser-Pro-Ser)4, a synthetic peptide homologous to the evolutionarily-conserved, tandemly-repeated heptapeptide sequence at the C-terminus of the large subunit of eukaryotic RNA polymerase II, has been detected in HeLa cell extracts and chromatographic fractions therefrom. The enzyme, which phosphorylates serine principally, can be distinguished from previously described major protein kinases which phosphorylate the peptide poorly, if at all. It is inhibited by the nucleoside analog, 5,6 dichloro-1-beta-D-ribofuranosylbenzimidazole. Results suggest that human placental RNA polymerase II is phosphorylated at the C-terminus of the large subunit by the partially-purified protein kinase and that the phosphorylation is also sensitive to the nucleoside analog. PMID- 2930528 TI - Elevated levels of calcitonin mRNA: a marker for the spontaneous development of medullary thyroid carcinoma in rats. AB - The aging WAG/Rij rats (a Wistar derived strain) develop spontaneously medullary thyroid carcinoma with a high frequency (50%). We have studied calcitonin biosynthesis in Wistar and WAG/Rij rats strains in order to determine if early changes in this parameter occurred in the WAG/Rij strain. Thyroidal and plasma CT levels were measured in three months old WAG/Rij and Wistar rats before and after acute calcium challenge. Total RNA was extracted from thyroid glands and specific CT messenger RNA levels estimated by dot and Northern blot analysis with a 32P labeled probe specific for CT mRNA. The capacity of mRNA to direct synthesis of CT precursor was also measured by translation in an in vitro system. Though mean basal circulating CT levels were equivalent in both strains, CT release after calcium stimulation was much increased in the WAG/Rij rat. CT content of the glands and CT mRNA levels were two fold higher in the WAG/Rij strain. Thus, in this strain, CT biosynthesis and secretion were increased long before the development of a C-cell carcinoma. PMID- 2930529 TI - Anti-liver-kidney microsome antibody type 1 recognizes human cytochrome P450 db1. AB - Anti-liver-kidney microsome antibody type 1 (LKM1), present in the sera of a group of children with autoimmune hepatitis, was recently shown to recognize a 50 kDa protein identified as rat liver cytochromes P450 db1 and db2. High homology between these two members of the rat P450 IID subfamily and human P450 db1 suggested that anti-LKM1 antibody is directed against this human protein. To test this hypothesis, a human liver cDNA expression library in phage lambda GT-11 was screened using rat P450 db1 cDNA as a probe. Two human cDNA clones were found to be identical to human P450 db1 by restriction mapping. Immunoblot analysis using as antigen, the purified fusion protein from one of the human cDNA clones showed that only anti-LKM1 with anti-50 kDa reactivity recognized the fusion protein. This fusion protein was further used to develop an ELISA test that was shown to be specific for sera of children with this disease. These results: 1) identify the human liver antigen recognized by anti-LKM1 auto-antibodies as cytochrome P450 db1, 2) allow to speculate that mutation on the human P450 db1 gene could alter its expression in the hepatocyte and make it auto-antigenic, 3) provide a simple and specific diagnostic test for this disease. PMID- 2930530 TI - Supramolecular surfactants: amphiphilic polymers designed to disrupt lipid membranes. AB - Simple polyesters derived from poly(ethylene glycol)s and alpha, omega dicarboxylic acids exhibit a broad range of activity in disrupting phospholipid membranes. This activity has been analyzed by measuring the release of liposome encapsulated 5(6)-carboxy-fluorescein (CF). Comparison with an analogous monomeric surfactant, and with Triton X-100, demonstrates that macromolecular activity is a sensitive function of the size of the hydrophobic and hydrophilic segments within each repeat unit, and that high disrupting power is possible. In vitro studies with the human immunodeficiency virus type-1 have revealed that those polyesters which exhibit the highest membrane disrupting power also provide significant protection for human CD4+ lymphocytes against HIV-1. The potential for adjusting and utilizing these "supramolecular surfactants" in medicine is briefly discussed. PMID- 2930531 TI - Human testicular lactate dehydrogenase-C gene is interrupted by six introns at positions homologous to those of LDH-A (muscle) and LDH-B (heart) genes. AB - Human genomic clones containing parts of testis-specific lactate dehydrogenase-C gene of approximately 40 kilobases in length were isolated and characterized. The protein-coding sequence of human LDH-C gene is interrupted by six introns at positions homologous to those of mammalian LDH-A (muscle) and LDH-B (heart) genes, and exhibits 21%, 24% and 34% nucleotide differences with those of mouse LDH-C, human LDH-A and LDH-B genes, respectively. PMID- 2930532 TI - Experimental evidence of an alpha helix in Desulfovibrio desulfuricans Norway ferredoxin I: a two-dimensional NMR study. AB - Desulfovibrio ferredoxins are small proteins involved in biological oxido reduction reactions and contain either one or two (4Fe-4S) clusters. The conformation of D. desulfuricans Norway ferredoxin I in solution was studied by two-dimensional NMR and various conformational parameters (n.O.e. and J-coupling) indicate the presence of an alpha-helix involving residues 41 to 50. These data confirm an earlier proposal (Fukuyama et al, J. Mol. Biol. 199, 183 (1988] in which the space of the missing cluster in monocluster ferredoxins is occupied by an alpha-helix. The evolutionary relevance of this result is discussed in view of published sequences and structures of related ferredoxins. PMID- 2930533 TI - Sequence determination in oligosaccharides by relayed NOE experiments in the rotating frame. AB - An hybrid experiment, composed of 1H-NMR total correlation spectroscopy (TOCSY) and rotating frame nuclear Overhauser enhancement spectroscopy (ROESY) steps, makes it possible to determine both the partial (disaccharide) sequences, and the sequential order, of whole linear and branched oligosaccharide chains. PMID- 2930534 TI - Voltage-dependent introduction of a d[alpha]octothymidylate into electropermeabilized cells. AB - DC-3F cells were submitted to electric square wave pulses in the presence of a d[alpha]octothymidylate 32P labelled in the 5' position. Radioactivity was incorporated in a voltage-dependent manner and reached a maximum for a field intensity of 1300-1400 V.cm-1. Growth curves and parallel cloning efficiency experiments indicated that cell viability was not altered by electric pulses, alone or in the presence of the oligothymidylate, below a field intensity of 1300 V.cm-1. Using affinity chromatography we extracted the incorporated oligonucleotide and showed that it was not degraded during the electropermeabilization experiment time. PMID- 2930535 TI - Degradation of trichloroethylene by the ammonia-oxidizing bacterium Nitrosomonas europaea. AB - Suspensions of Nitrosomonas europaea are shown to cause the complete disappearance of 10 microM trichloroethylene at rates of 1 microM mg protein-1. The reaction continues at nearly this rate for many hours. Fresh cells catalyze the reaction in the absence of added ammonium (presumably utilizing endogenous ammonia or stored reductant). In older cells, trichloroethylene degradation depends on the addition of ammonia. Acetylene, 2-chloro 6-trichloromethylpyridine and alpha alpha'dipyridyl, which inhibit the oxidation of ammonia by cells, inhibit the degradation of trichloroethylene. Thus degradation of trichloroethylene is dependent on- and possibly catalyzed by the ammonia oxidizing enzyme. PMID- 2930536 TI - Study of the heteromeric structure of the untransformed glucocorticoid receptor using chemical cross-linking and monoclonal antibodies against the 90K heat-shock protein. AB - The untransformed rat glucocorticoid receptor is assumed to be a hetero oligomeric complex, containing a non-steroid binding component, the 90K heat shock protein (HSP 90). Direct measurement of its molecular weight by chemical cross-linking provides new evidence for a trimeric structure with a Mr of ca. 270,000. Resorting to an anti HSP 90 probe (AC 88), we show that the native dimeric HSP 90 possess two accessible epitopes for this monoclonal antibody, while when bound to the steroid-binding subunit, only one epitope remains accessible. These data clearly suggest that the untransformed rat glucocorticoid receptor is an asymmetrical hetero-oligomeric complex. PMID- 2930537 TI - Ontogeny of pineal protein kinase C activity. AB - The developmental appearance of protein kinase C (PKC) activity in the rat pineal gland was investigated. Enzyme activity could be detected before birth in both cytosol and membrane fractions. A small peak in activity was seen between -2 and 4 days of age, coinciding with a temporary redistribution of activity to the membrane fraction (4% increasing to 17%). After 10 days of age both cytosol and membrane activity increased progressively to reach adult levels by 30 days. Inhibition of daily adrenergic stimulation to the gland by decentralizing or removing the superior cervical ganglia or exposing rats to constant light for 14 days did not reduce PKC activity. These results indicate that PKC activity is located in pinealocytes rather than in the presynaptic adrenergic terminals and that adrenergic stimulation is not necessary to maintain the high level of PKC activity in the pineal. PMID- 2930538 TI - Neutralization of cholera toxin by rat IgA secretory antibodies induced by a free synthetic peptide. AB - Secretory immunoglobulin A (sIgA) is the major immunoglobulin in the bile of several species. They contribute to local immune defences of the gut. The protection against cholera toxin (CT) is due to the presence of specific sIgA in the bile and in the gut. We have already reported that oral administration of the peptide corresponding to the sequence 50-75 of cholera toxin B subunit elicits serum antibodies neutralizing CT activity, and that IgA and local protection are observed in the intestine of P50-75 orally immunized mice. In this study, we demonstrate the potential of this synthetic peptide as immunogen without carrier or adjuvant, not only in a strain known to be sensitive to CT, but also in an outbred one. Furthermore, this peptide stimulates the mucosal immunity, since we show that P50-75 induced-sIgA purified from rats bile and serum, are capable of neutralizing CT activity in the in vivo intestinal ligated loop test. PMID- 2930540 TI - Alterations in the sialylation and sulfation of secreted mouse thyrotropin in primary hypothyroidism. AB - We investigated the effect of in vivo hypothyroidism on the sialylation and sulfation of thyroid-stimulating hormone (TSH) secreted by mouse pituitary explants. Oligosaccharides from secreted thyroid-stimulating hormone from hypothyroid animals contained greater sialic acid relative to sulfate in both alpha and beta subunits. Aging per se had little effect on thyroid-stimulating hormone sialylation or sulfation. Variable sialylation and sulfation demonstrates a mechanism for charge microheterogeneity of thyroid-stimulating hormone, and the increasing sialylation observed with hypothyroidism may functionally mediate the prolonged metabolic clearance that has been noted previously. PMID- 2930539 TI - A tumor growth inhibitory factor and a tumor growth promoting factor isolated from unfertilized ova of shad (Alosa sapidissima). AB - In the present study, a cytostatic tumor growth inhibitory peptide and a tumor growth promoting peptide with molecular weights of 20,000-30,000 Da have been identified in the supernatant fraction of unfertilized ova from Shad. The factors can be separated by gel chromatography, thus indicating that the factors are individual molecules. Both of the factors are nondialyzable, heat stable, and resistant to trypsin digestion and periodate oxidation. PMID- 2930541 TI - Lack of effect of pertussis toxin on TNF-alpha-induced formation of reactive oxygen intermediates by human neutrophils. AB - When human PMN were plated on fetal calf serum-coated polystyrene surfaces, addition of TNF-alpha, FMLP or PMA elicited adhesion and H2O2 formation. These effects of TNF-alpha and FMLP, but not of PMA, were impaired by removal of extracellular Ca2+. In addition, H2O2 formation induced by FMLP but not by TNF alpha or PMA was inhibited by prior treatment with pertussis toxin (250-500 ng/ml). Thus, although the sequelae of TNF-alpha-receptor interaction on human PMN remain to be characterized in detail, they do not involve a pertussis toxin sensitive GTP-binding protein. PMID- 2930542 TI - The integrity of tubulin molecule is not required for the activity of tubulin carboxypeptidase. AB - Tubulin dimer, alpha-tubulin subunit, and C-terminal peptides obtained from the alpha-tubulin subunit were compared in their capabilities to act as substrates of tubulin carboxypeptidase. The results obtained indicate that the enzyme does not require the beta-tubulin subunit to release tyrosine from alpha-tubulin. The 17 Kd C-terminal peptide of the alpha-tubulin subunit was obtained and it was detyrosinated at the same rate as tubulin dimer. A smaller C-terminal peptide of 2.8-3.7 Kd showed a lower capability to act as substrate. Similar results were obtained with pancreatic carboxypeptidase A. From the analysis of the results we consider that an optimal activity of the tubulin carboxypeptidase depends mainly on the accessibility of the C-terminal end of alpha-tubulin. PMID- 2930543 TI - Spermine antagonizes the binding of adriamycin to the inner membrane of heart mitochondria. AB - The biologically active polyamine, spermine, has been found to function as a cationic antagonist of adriamycin binding to ox heart submitochondrial particles. This effect is specifically shown by spermine since other cations tested in the same conditions, can antagonize the binding only to a very low extent. Analysis of the adriamycin binding data in the presence of spermine indicate that the polyamine can greatly reduce the total number of binding sites for the anthracycline in submitochondrial particles and it can increase the apparent dissociation constant, whilst it leaves unchanged the degree of cooperativity of the binding. These results provide evidence on previously unexplored effects of spermine, suggesting that this polyamine might be examined as a possible in vivo antagonist of the adriamycin binding to mitochondria. PMID- 2930544 TI - In vivo 31P NMR spectroscopy of energy rich phosphates in the brain of the hyperammonemic rat. AB - Hyperammonemia is a major contributing factor to the neurological abnormalities observed in hepatic encephalopathy and in congenital defects of ammonia detoxication. In rats variable changes in labile energy rich phosphates in the brain have been observed in hyperammonemia using biochemical methods. Using 31P NMR spectroscopy however no significant changes of the relative concentrations of the energy rich phosphates alpha, beta and gamma-ATP, phosphocreatine, inorganic phosphate and the pH were found in the fronto parietal cortex of the urease treated hyperammonemic rat. Alterations in the metabolites of these compounds do not appear to be a major pathomechanism of ammonia toxicity in this brain area. PMID- 2930545 TI - Microtubule-associated protein-2 stimulates DNA synthesis catalyzed by the nuclear matrix. AB - Microtubule-associated protein-2 (MAP-2) isolated from porcine brains stimulated DNA synthesis catalyzed by the nuclear matrix isolated from Physarum polycephalum in the presence of activated DNA as exogenous templates. The degree of the stimulation depended on the amount of the nuclear matrix, but not on that of the template. MAP-2 also stimulated DNA polymerase alpha activity solubilized from nuclei, but not DNA polymerase beta activity. These results suggest that MAP-2 stimulates DNA synthesis by interacting with the putative DNA replication machinery including DNA polymerase alpha bound to the matrix. Similar stimulation occurred in the nuclear matrix isolated from HeLa and rat ascites hepatoma cells, which strongly suggests that MAP-2 is involved in the control of DNA replication in eukaryotic cells. PMID- 2930546 TI - [Ca2+]i independent mitogenesis in cultured human fibroblasts revealed by single cell microfluorimetry. AB - A transient rise in intracellular free Ca2+ concentration ([Ca2+]i) has been implicated in mitogenic induction of cell division. Individual human foreskin fibroblasts in confluent cultures examined with the Ca2+ indicator Fura-2 and a fluorescence microscope-imaging system had a basal [Ca2+]i which varied markedly from cell-to-cell. A transient serum-induced rise in [Ca2+]i was demonstrated the magnitude of which was directly correlated with the basal [Ca2+]i level. In contrast to serum-induced increase in [Ca2+]i, exposure to an elevated level of extracellular Ca2+, which is at least equally mitogenic for fibroblasts, did not alter the basal [Ca2+]i of single subconfluent cells or confluent cells. Elevated extracellular Ca2+ does not exert its mitogenicity via a transient rise in [Ca2+]i. PMID- 2930547 TI - Regulation of colony formation of differentiated chondrocytes in soft agar by transforming growth factor-beta. AB - Fibroblast growth factor (FGF) induces colony formation by chondrocytes in soft agar (Y. Kato et al., J. Cell. Physiol., 1987), and the present study revealed that transforming growth factor-beta(TGF-beta) does not induce the same effect. TGF-beta did, however, increase the efficiency of colony formation by chondrocytes 3- to 4-fold in the presence of a maximal dose of FGF. Furthermore, TGF-beta decreased the concentrations of FGF needed for the induction of cell growth in soft agar by 40- to 100-fold. These results suggest that TGF-beta is involved in the control of cartilage growth possibly by increasing the responsiveness of chondrocytes to FGF. PMID- 2930548 TI - Fatty acid composition of lipids which copurify with band 3. AB - In a previous study (L. R. Maneri and P. S. Low (1988) J. Biol. Chem. 263, 16170 16178) we determined that the anion transport protein, band 3, was significantly stabilized by lipids containing saturated and/or long chain fatty acids. To determine whether this thermodynamic preference is reflected in the composition of lipids tightly associating with the anion transporter in vivo, we have analyzed the fatty acid content of phospholipids co-isolating with the purified integral domain of band 3. Our data demonstrate that although stearic acid comprises only 14% of the bulk lipid fatty acids of the red cell membrane, it constitutes -68% of the fatty acids of lipids co-isolating with band 3. Certain other long chain fatty acids were also enriched in the adherent lipids. These results suggest that the fatty acids which most effectively stabilize band 3 also have the highest affinity for the transport protein. PMID- 2930549 TI - Potentiation of diacylglycerol-activated protein kinase C by acyl-coenzyme A thioesters of hypolipidaemic drugs. AB - Acyl-Coenzyme A thioesters of the hypolipidaemic and cancerinogenic peroxisome proliferators clofibric acid, nafenopin, ciprofibrate, bezafibrate and tibric acid were found to greatly increase the activity of rat brain protein kinase C. Maximal activation required the simultaneous presence of Ca+2, phosphatidylserine and diolein, thus differentiating their action from that of other tumor promoters such as phorbol esters. Under similar conditions the unesterified drugs were comparatively ineffective. Similar results were obtained using the rat liver enzyme. The data suggest that acylcoenzyme A thioesters of hypolipidaemic drugs, may play a role in the induction of liver tumors by these compounds, through the potentiation of protein kinase C. PMID- 2930550 TI - Singlet oxygen production from the peroxidase catalyzed formation of styrene glutathione adducts. AB - Recently, Stock et al. (J. Biol. Chem. 261, 15915-15922 [1986]) described a model enzyme system composed of horseradish peroxidase, hydrogen peroxide, phenol, glutathione and styrene. This system forms glutathione-styrene conjugates. Glutathione radicals and carbon-centered radicals are intermediates in this process. In the present study, this model enzyme system was also shown to generate singlet oxygen, probably via a Russell mechanism. No singlet oxygen was generated in the absence of styrene. Thus, contrary to prior suggestions, the reaction of glutathione radical with oxygen to produce a thiyl peroxyl radical is not a significant source of singlet oxygen. PMID- 2930551 TI - The reactions of chloroperoxidase in the presence of xanthine/xanthine oxidase. AB - Spectral data are presented which indicate that chloroperoxidase is converted to compound II during the reaction with superoxide/hydrogen peroxide generated in the xanthine/xanthine oxidase system. Upon completion of compound II formation, compound II returns back to the native state of chloroperoxidase without formation of detectable intermediates. It is shown that chloroperoxidase acts as a superoxide scavenger but less effectively than superoxide dismutase. Addition of chloride ion enhances the rate of decay of compound II to native enzyme, showing that chloride ion is oxidized to a chlorine atom in the presence of compound II. PMID- 2930552 TI - Dual effect of activin A on cell growth in Balb/c 3T3 cells. AB - Effects of activin A on cell growth were studied in Balb/c 3T3 cells. When incubated with serum, activin A inhibited serum-induced increase in DNA synthesis in a concentration-dependent manner. Activin A also inhibited serum-induced increase in cell number. When added in quiescent cells, activin A did not affect competence-inducing activity of PDGF. Activin A by itself had a small competence inducing activity. In contrast, when added in competent cells, activin A inhibited progression activity of platelet-poor plasma. These results indicate that activin A has dual action on cell proliferation in Balb/c 3T3 cells. PMID- 2930553 TI - Adverse effects of anti-tumor drug, cisplatin, on rat kidney mitochondria: disturbances in glutathione peroxidase activity. AB - This study was designed to clarify mechanisms responsible for cisplatin-induced nephrotoxicity together with the effect of selenium. Rats were divided into 3 groups: the cisplatin group; cisplatin (60 mg/kg) was administered intraperitoneally once, the cisplatin + Se group; cisplatin (60 mg/kg) once, and selenious acid (10 mumol/kg) were administered intraperitoneally once a day for 5 consecutive days, the control group; untreated. In each group, mitochondrial respiratory function, enzymic activities in mitochondrial respiratory chain and glutathione peroxidase, and plasma creatinine and BUN contents were measured. In the cisplatin group, decreases in mitochondrial respiratory function, enzymic activities in the respiratory chain and glutathione peroxidase, and increases in plasma creatinine and BUN contents were observed compared with the control group, while the cisplatin + Se group lessened these impairments. These results suggested that cisplatin-induced nephrotoxicity was closely related to mitochondrial dysfunction through the impairment of glutathione peroxidase. This toxicity might be ascribed to free radical mediated-injury. We propose here that, with selenium, higher dose administration of cisplatin to patients might be applicable. PMID- 2930554 TI - Evidence for the formation of 26-hydroxycholesterol by cytochrome P-450 in pig kidney mitochondria. AB - Pig kidney mitochondria were found to catalyze the formation of 26 hydroxycholesterol, an inhibitor of cholesterol biosynthesis. The cholesterol 26 hydroxylase was purified 600-fold. It was present in a mitochondrial enzyme fraction enriched in cytochrome P-450. The cytochrome P-450 fraction required NADPH, mitochondrial ferredoxin and ferredoxin reductase for 26-hydroxylase activity. The mitochondria and the purified 26-hydroxylase preparation also catalyzed 26-hydroxylation of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol, and intermediate in cholic acid biosynthesis, and of 25-hydroxyvitamin D3. The role of extra-hepatic formation of 26-hydroxycholesterol is discussed. PMID- 2930555 TI - ADP-ribosylatable content of elongation factor-2 changes during cell cycle of normal and cancerous human cells. AB - The amount of protein elongation factor EF-2 that can be inactivated by diphtheria toxin-mediated ADP-ribosylation, a measure of its active content, decreases by 45% and 66% in G1-arrested normal human fibroblasts and in HeLa cells respectively. On restimulation of cells with fresh serum, the amounts of ADP-ribosylatable EF-2 begin to increase within 4 h. Whereas the level of active EF-2 returns to normal (exponential phase of growth) in 20 h in the case of fibroblasts, only 47% recovery was observed for HeLa cells during this period. The apparent long half-lives of EF-2 mRNA and protein indicate possibilities of posttranslational ADP-ribosylation and de-ADP-ribosylation as the regulators of the amounts of active EF-2 during human cell cycle. PMID- 2930556 TI - The formation of glyoxylate from glycine by melanin. AB - Natural and synthetic melanins catalyze the conversion of glycine to glyoxylate and formic acid in vitro. The conversion depends upon the concentration of melanin. PMID- 2930557 TI - Amphotericin B-induced changes in renal membrane permeation: a model of nephrotoxicity. AB - As part of an investigation into the nephrotoxic effects of the polyene antibiotic Amphotericin B we have studied its effects on the ion permeability of purified renal brush border membrane vesicles. Membrane potentials were measured using a potential sensitive carbocyanine dye, and ion permeabilities were calculated from the constant field equation. Amphotericin B significantly altered the ionic permeability sequence of isolated membranes and caused a selectivity for increasing the permeation of anions. Permeability changes induced by 2.0 micrograms/ml Amphotericin B resulted in an estimated hyperpolarization of the membrane from -50 mV to -72 mV. In addition, the kinetic parameters of Na+ dependent transport of organic metabolites were examined. The maximum change in fluorescence was decreased significantly in the presence of Amphotericin B. These results suggest that the ionic state of the renal cell membrane is significantly altered by the presence of Amphotericin B. PMID- 2930558 TI - Prostaglandin D2 stimulates calcification of human osteoblastic cells. AB - Studies on prostaglandin (PG) regulation of bone formation and resorption metabolism have been complicated by the heterogeneity of the tissue, which involves the interaction between and the activities of two bone cell types, osteoblasts and osteoclasts. In a simplified assay system using a cultured human osteoblastic cell line which has the capacity to form calcified tissue, we determined the effects of PGs on calcification. Of the PGs tested, PGD2 has a remarkable stimulatory activity on osteoblast calcification, but that the effective form is probably a metabolite, delta 12-PGJ2. This calcification function is not cAMP-mediated. PGD2 acts directly on osteoblast to cause stimulation of calcification. PMID- 2930559 TI - Chromophore conformational analysis in phycocyanin and in related chromopeptides by surface enhanced Raman spectroscopy. AB - Chromopeptides got from phycocyanin by proteolytic digestion do not preserve the extended chromophore conformations characteristic to the native protein. Chromophore conformations in the chromopeptides showed heterogenity varying between completely folded and semi-extended states. Indications were found that the silver sol-phycocyanin interaction involves the UV electronic transition of the biliprotein which may explain why the visible excited surface enhanced Raman spectra were similar not to the visible excited but to the UV-excited resonance Raman spectrum of phycocyanin. PMID- 2930560 TI - Titration of variant DNA sequences differing by a single point-mutation by selective dot-blot hybridization with synthetic oligonucleotides. AB - A dot-blot hybridization procedure with synthetic oligonucleotide probes is reported, which allows the quantitative titration in genomic DNA of variant forms of repeated genes differing by a single nucleotide change. It involves the utilization of a pair of 22-base long oligonucleotides matching the two variant sequences and the choice of an hybridization temperature very close to the Td of the oligonucleotide/DNA duplexes. The selectivity is achieved through a competition between the cognate labeled and the non-cognate unlabeled probes in the hybridization mixture. PMID- 2930561 TI - Tight binding of a copper (II) phthalocyanine (cuprolinic blue) to DNA. AB - The binding of a cationic phthalocyanine (Cuprolinic Blue) to calf thymus DNA, indicated by the increase in the DNA melting temperature and spectroscopic titration (Kaff greater than 10(7)M-1), was characterised by at least two distinct DNA-bound ligand forms possibly arising from intercalated and externally bound species each with Kaff values in the region 10(7) M-1. Evidence of strong intercalation was provided by gel electrophoresis of plasmid DNA in the presence of Cuprolinic Blue. The anionic phthalocyanine (copper phthalocyanine 3,4',4", 4"'-tetrasulfonic acid) does not bind to DNA by spectral criteria, reflecting electrostatic contributions to binding. PMID- 2930562 TI - Inhibin alpha-subunit monomer is present in bovine follicular fluid. AB - The 26 kDa form of the inhibin alpha-subunit monomer was isolated from bovine follicular fluid. Both sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting analysis revealed that the 26 kDa form of the alpha-subunit monomer is composed of 6 kDa and 20 kDa fragments linked together by a disulfide bond(s). The NH2-terminal sequence and amino acid analyses of each fragment showed that those fragments are derived from residues 18 to 60 and 227 to 360, respectively, of the inhibin alpha-subunit precursor (residues 1 to 360) as deduced from the cDNA sequence. Thus, it is concluded that removal of the putative signal peptide (residues 1 to 17) and the middle portion (residues 61 to 226) from the alpha-subunit precursor generates the 26 kDa form of the alpha subunit. In the in vitro rat pituitary assay, the 26 kDa alpha-subunit exhibited neither inhibin-like nor FSH-release stimulating activity. PMID- 2930563 TI - A micellar model for investigating the chemical nature of hydrogen transfer in NAD(P)H-dependent enzymatic reactions. AB - Aqueous micelles of Triton X-100 were shown to catalyse the redox reaction between NADH and 2-p-iodophenyl-3-p-nitrophenyl-5-phenyltetrazolium chloride (INT) at the neutral pH. The transfer of reducing equivalents between the reactants in the micellar system appeared to be direct and quantitative. N-tert butylphenyl-alpha-nitrone, a lipophilic free-radical scavenger which can enter micelles, and superoxide dismutase did not alter the stoichiometry of the reaction. The oxidation product of NADH was found to be 100% enzymatically active. The IR spectrum of INT-formazan (i.e., the product of INT reduction) showed an absorbance at 3,100-3,700 cm- due to NH-stretching. The presence of NH proton, confirmed further by IH-NMR, together with the above observations suggests that INT, as part of the over-all redox process, abstracts a C(4) hydrogen of the dihydropyridine nucleus of NADH with a simultaneous cleavage at N(2-3) position of its 1,2,3,4-tetrazole ring system and that the redox events are confined to a microenvironment as in the case of NAD(P)H-dependent enzymatic reactions. PMID- 2930564 TI - Direct evidence for modulation of porter quaternary structure by transport site ligands. AB - The transport inhibitor DNDS (4,4'-dinitrostilbene-2,2'-disulfonate) changes the bis(sulfosuccinimidyl)suberate (BS3) crosslinking pattern of band 3 protein from a mixture of dimer-crosslinkable (DC) and tetramer-crosslinkable (TC) states to the TC-state as the exclusive crosslinked product for reactions occurring in membranes of intact human erythrocytes. Pretreatment of cells with DNDS followed by extensive washing restores the original DC to TC proportionality indicating that the two states are reversibly interconvertible. We suggest a model wherein band 3 transport site ligands allosterically modulate the global conformation of a tetrameric porter between two reversibly interconvertible quaternary structures. These transitions in quaternary structure may be important to transmembrane signaling of events between the exofacial ligand binding site and the sites on the porter extension which bind ankyrin and hemoglobin. PMID- 2930565 TI - Parathyroid hormone 1-34, but not 3-34 or 7-34, transiently translocates protein kinase C in cultured renal (OK) cells. AB - While protein kinase C (PKC) appears to play a role in the action of PTH in renal cells, direct evidence of activation by PTH is lacking. Rat PTH (1-34) caused a rapid, transient translocation of PKC in opossum kidney (OK) cells from a basal value of 0.09 to maximum of 0.24 at 10-15 sec. Both the time course and dose response relationship of translocation matched a corresponding increase in cytosolic Ca2+. In contrast, PTH activation of cAMP-dependent protein kinase (PKA), while also rapid, was greater in magnitude (0.10 to 0.50), persistent, and occurred at a threshold level of 3 x 10(-10)M PTH, compared to 10(-8)M for PKC. Neither bPTH(3-34) nor bPTH(7-34) activated either protein kinase, while both antagonized rPTH(1-34)-induced PKC translocation more effectively than PKA activation. These differential effects of PTH agonist and antagonists further support the suggestion that PTH acts through two signal transduction mechanisms in which one or more receptors is linked in distinct ways to adenylate cyclase and phospholipase C. PMID- 2930566 TI - Cremophor EL, a widely used parenteral vehicle, is a potent inhibitor of protein kinase C. AB - Cremophor EL, a castor oil derivative, has been considered a non-toxic solubilizer for lipophilic drugs and vitamins. Protein kinase C, a phospholipid/Ca++-dependent protein kinase, is known to phosphorylate, in response to extracellular stimuli, a variety of proteins for cellular functions. The present study shows that Cremophor EL selectively inhibits the activity of protein kinase C in vitro. The potency of this selective inhibition is greater than that of other protein kinase C-specific inhibitor thus far reported. Cremophor EL acts primarily on the enzyme activator diacylglycerol (or the phorbol ester) and prevents the latter from both interacting with the phospholipid and binding to protein kinase C. This is the first report of a significant biological activity induced by this widely used substituted castor oil solubilizer. PMID- 2930567 TI - Multiple receptors for modified low density lipoproteins in mouse peritoneal macrophages: different uptake mechanisms for acetylated and oxidized low density lipoproteins. AB - Receptor-mediated incorporations of two modified low density lipoproteins (LDL), acetylated LDL (acetyl-LDL) and oxidized LDL were compared in vitro in mouse peritoneal macrophages by cross-competition experiments. Excess amount of oxidized LDL inhibits the binding of [125I]acetyl-LDL only partially, and excess amount of acetyl-LDL inhibits that of [125I]oxidized LDL also only partially, suggesting that the uptake of the two LDL by macrophages is mediated by partially overlapped yet different mechanisms. Scatchard analysis of [125I]acetyl-LDL binding showed a linear plot and addition of excess amount of oxidized LDL partially displaced the binding sites without changing the affinity, suggesting that there are two classes of receptors with similar affinity; one is specific for acetyl-LDL and the other is common. And the plot of [125I]oxidized LDL binding showed a curvilinear plot and excess amount of acetyl-LDL partially displaced the binding sites of the low affinity, suggesting that there are two classes of binding sites with different affinities and the low affinity one is shared with acetyl-LDL. These results indicate that macrophage receptors for modified LDL consist of at least three receptors, two of which are specific for each LDL and the rest is a common receptor. PMID- 2930568 TI - Regulation of new osteoclast formation by a bone cell-derived macromolecular factor. AB - Medium conditioned by incubation with embryonic chick calvarial bones, which contain osteoblasts but not osteoclasts, stimulated new osteoclast formation in foetal long bone cultures and in adult bone marrow cultures formation of tartrate resistant acid phosphatase (TRAP) positive cells was greatly stimulated. We have termed the factor responsible for this activity osteoclast growth/inducing factor (OGF). OGF was soluble, heat-stable and of size greater than 10kda. OGF activity was present also in mouse bone conditioned medium and in extracts of demineralized cortical diaphyseal bone of five-week-old chickens. OGF appeared to differ from the osteoblast-derived bone-resorbing factors previously observed as well as from macrophage colony stimulating factor (CSF-1). It is therefore probable that different locally secreted factors independently regulate the formation of osteoclasts and their activity. PMID- 2930569 TI - DNA polymerase alpha activity is not affected by protein kinases or alkaline phosphatase. AB - Recent studies with crude or partially purified cell extracts have suggested that DNA polymerase alpha activity may be regulated by enzymatic phosphorylation. To further investigate these findings, we have examined the effects of protein kinases and phosphatases on highly purified DNA polymerase alpha from mouse cells. Incubation of DNA polymerase alpha with a variety of protein kinases, including protein kinase C, had no effect on polymerase activity. In addition, treatment of the polymerase with soluble calf intestinal alkaline phosphatase had no effect on DNA polymerase alpha activity, further indicating that phosphorylation does not have a direct role in modulating polymerase activity. In contrast, incubation of DNA polymerase alpha with calf intestinal alkaline phosphatase crosslinked to agarose beads resulted in a time dependent disappearance of polymerase activity. This loss of DNA polymerase activity was dependent on phosphatase activity, as the alkaline phosphatase inhibitors, potassium phosphate or levamisole, prevented the loss of polymerase activity in the presence of the beaded phosphatase. The loss of DNA polymerase alpha activity following beaded phosphatase treatment was not a general phenomena as the large fragment of Escherichia coli DNA polymerase I, T4 DNA polymerase or mouse primase were not affected by similar treatment. The decreased DNA polymerase activity following incubation with phosphatase beads correlated with the binding of the DNA polymerase polypeptides, p185 and p68, to the agarose beads and this binding could not be reversed by either 150 mM potassium chloride or sodium sulfate. The binding of the polymerase to the agarose beads was dependent on the phosphatase activity, as the polymerase could be first treated with soluble calf intestinal phosphatase and subsequently bound to added Sepharose 4B beads. Surprisingly, Sepharose CL4B, a highly desulfated agarose preparation, did not bind the phosphatase-treated polymerase suggesting that sulfated polysaccharides are required for polymerase binding. The physiological correlate of this binding is unknown, but it has been reported that sulfated polysaccharides exist in a variety of intracellular compartments. It would be interesting to speculate that phosphorylation controls the intracellular compartmentalization of DNA polymerase alpha. PMID- 2930570 TI - Structure determination of the UDP-disaccharide fragment of cytoplasmic cofactor isolated from Methanobacterium thermoautotrophicum. AB - The methylcoenzyme M methylreductase reaction has an absolute requirement for 7 mercaptoheptanoylthreonine phosphate or component B, which is the active component of the intact molecule previously referred to as cytoplasmic cofactor. A hydrolytic fragment of cytoplasmic cofactor has been purified and identified as uridine 5'-(O-2-acetamido-2-deoxy-beta-manno-pyranuronosyl acid (1----4)-2 acetamido-2-deoxy-alpha-glucopyranosyl diphosphate) by high resolution NMR and fast atom bombardment mass spectro-metry. It is postulated that UDP-disaccharide may function to anchor 7-mercaptoheptanoyl threonine phosphate at the active site of the methyl-reductase enzyme complex. PMID- 2930571 TI - A revised sequence of calf thymus glutaredoxin. AB - The previously published structure of the glutaredoxin from calf thymus [Klintrot et al., (1984) Eur. J. Biochem. 144, 417-423] was reinvestigated by tandem mass spectrometry and found to have an N-terminal Ac-Ala-Gln-Ala-... sequence and an additional four amino acids inserted between positions 67 and 68. PMID- 2930572 TI - Distance estimation from NOE data in macromolecular systems: a quadratic approach. AB - A new procedure has been suggested for the estimation of interproton distances from Nuclear Overhauser Enhancement (NOE) data in biological macromolecules. A critical assessment of the errors and advantages has been made vis a vis the commonly used initial rate approximation. Experimental data supporting the theoretical ideas have been presented. PMID- 2930573 TI - Biological and chemical evidence for the existence of a porcine hypothalamic parotid hormone-releasing factor. AB - Methodology has been developed to achieve partial purification of a parotid hormone-releasing peptide from porcine hypothalamus-thalamus tissue using an in vivo parotid hormone stimulation test in pigs and a dentinal fluid transport stimulation test in rats. The purification steps include: acetone-water extraction of the tissue at pH 5.2, ultrafiltration through Amicon PM10 membrane, size exclusion chromatography on Bio-Gel P2, and open-column reversed-phase chromatography on Lichroprep RP8. A 100-fold increase in specific activity was attained. Intravenous infusion of porcine hypothalamus-thalamus extract stimulates a dentinal fluid transport mechanism in teeth of intact anesthetized rats, and the release of plasma immunoreactive parotid hormone in conscious catheterized pigs. Parotidectomy in both species suppresses the response, suggesting that the expression of parotid hormone-releasing activity requires the integrity of a putative hypothalamus-parotid gland endocrine axis. PMID- 2930574 TI - Apparent "activation" of protein kinases by okadaic acid class tumor promoters. AB - A cytosolic fraction of mouse brain gave two peaks of protein kinase activity on DEAE-cellulose column chromatography. The first peak of protein kinase corresponded to protein kinase C. The second peak contained protein kinases that were "activated" dose-dependently by the okadaic acid class tumor promoters, okadaic acid and dinophysistoxin-1. This "activation" was not achieved by other tumor promoters, such as 12-0-tetradecanoyl-phorbol-13-acetate, teleocidin, aplysiatoxin, or palytoxin. In addition, the second peak contained phosphatases. The phosphate liberation from phosphorylated histone type III-S by incubation with the second peak was inhibited by okadaic acid or dinophysistoxin-1, dose dependently. The resulting apparent "activation" of protein kinases by okadaic acid is indicated and would imply a new pathway of tumor promotion on mouse skin. PMID- 2930575 TI - Specific alterations in the biological activities of C-20'-modified vinblastine congeners. AB - Both the anti-tumor and toxic activities of the vinca alkaloid dimers, vinblastine (VBL) and vincristine (VCR), may reside at the level of their known cellular target, the microtubule system. The contributions made by each of the various actions of these alkaloids on this system are unknown. We have used new, complete synthetic methodologies to create a series of eight C-20' alkyl congeners of VBL and have examined these compounds for their abilities to (1) inhibit microtubule assembly, (2) disassemble preformed microtubules, and (3) induce spiral aggregate formation, using purified brain microtubule protein. By combining turbidimetric and electron microscopic techniques, we discovered that each of the various effects of VBL on the microtubule system in vitro was amenable to alteration by specific modification at this single molecular site. In addition, we report two new aberrations of VBL action--the induction of spirals by a concentration of congener below 1 microM and the formation of "opened" microtubules polymerized in the presence of congener. The relationship between anti-microtubule action in vitro and the cellular activities of growth inhibition and mitotic arrest by the congeners was examined in leukemic and colon cancer cell lines. In general, we found that both cellular perturbations were correlated to the ability of the congeners to inhibit microtubule polymerization rather than to the actions of spiral formation or microtubule disassembly. These results are a breakthrough in the structure/function relationship of the vinca alkaloid dimers and should provide the means to determine the role of specific anti microtubule activities to the complex biological actions of these natural product drugs. PMID- 2930576 TI - Evidence for isoxicam binding to site I as a primary site and to site II as a secondary site of human serum albumin. AB - Isoxicam binding to HSA was studied using equilibrium dialysis and fluorescence methods. It was shown that this drug binds to or near site I (warfarin or azapropazone site) and to site II (the diazepam site) as a secondary site, although it is generally considered that their respective drug structural requirements are often exclusive. The binding parameters were calculated with different mathematical models; a site oriented model with or without fixing the number of binding sites as integer values and a stoichiometric model. The relevant results are in good agreement under the selected experimental conditions. The stoichiometric method indicates that no positive cooperativity occurred during the binding process but other interactions between the two sites cannot be excluded. PMID- 2930577 TI - Comparison of microsomal drug-metabolizing enzymes in 14 rat inbred strains. AB - Drug metabolic capacity in liver microsomes of 14 rat inbred strains was investigated. Cytochrome P-450 content as well as the following enzyme activities were measured: NADPH cyt. c(P-450) reductase (Red.), aminopyrine N-demethylase (APDM), ethoxycoumarin O-deethylase (ECOD), 1-naphthol: UDP glucuronosyltransferase (NGT) and hydrolysis of acetylsalicylic acid (ASA; measured at pH 5.5 and pH 7.4). All enzymes measured were found to exhibit statistically significant inter-strain differences. In males the enzyme activities varied over a 7.3-fold (ECOD) to 1.4-fold (cytochrome P-450) range. Other inter-strain differences were generally larger than 2-fold: ASA-hydrolysis at pH 5.5 and 7.4 (3.9- and 3.3-fold variation, respectively), NGT and Red. (2.1 fold variation) and APDM (1.8-fold variation). In females similar, but somewhat smaller inter-strain differences were observed. Correlations between different enzyme activities were generally poor (correlation coefficients r less than 0.7). An exception was the correlation between ASA-hydrolysis at pH 5.5 and pH 7.4 (r = 0.79). We conclude that ASA hydrolysis at pH 5.5 and 7.4 is mediated by the same enzyme or by coregulated enzymes and that all other activities are mediated by different or differentially regulated enzymes. Based on analysis of variance and subsequent inter-strain comparisons, all strains appear to express a unique profile of liver microsomal drug metabolism. No two strains are identical with respect to all activities measured. We suggest that differences between inbred rat strains and particularly the difference in balance between different enzymes in various strains can be used advantageously in pharmacological and toxicological experiments. PMID- 2930579 TI - Role of glutathione and its associated enzymes in multidrug-resistant human myeloma cells. AB - Multidrug resistance (MDR) is a phenomenon associated with the emergence of simultaneous cross-resistance to the cytotoxic action of a wide variety of structurally and functionally unrelated antineoplastic agents. The present study was undertaken to determine if 8226 human myeloma cells possessing the MDR phenotype had an increased ability to resist the intercalating drug doxorubicin (DOX) via glutathione-based detoxification systems. Glutathione S-transferase (GST) was isolated by affinity chromatography, and the enzyme activity was assessed using 1-chloro-2,4-dinitrobenzene (CDNB) and glutathione (GSH) as substrates. There was no difference in overall GST activity between the sensitive and resistant cells. Using a cDNA probe (pGTSS1-2) for the human placental, anionic GST isoenzyme, no overexpression of mRNA for this isoenzyme was noted in the resistant line. When glutathione peroxidase activity (GSH-px) was assessed using either H2O2 or cumene hydroperoxide as substrate, again there was no difference in enzyme activity. Non-protein sulfhydryl (NPSH) levels were found to be elevated significantly in the resistant 8226/DOX40 subline (19.2 +/- 0.1 nmol NPSH/10(6) cells) as compared to the drug-sensitive parental subline 8226/S (11.6 +/- 1.9 nmol NPSH/10(6) cells) (P less than 0.001). In addition, when the 8226/DOX40 cells were cultured in medium without doxorubicin, there was a consistent decline in NPSH values reaching a steady state identical to that of the 8226/S cells. However, the decrease in NPSH level was not accompanied by a change in the level of doxorubicin resistance as assessed by colony-forming assays. Depletion of glutathione by D,L-buthionine-S,R-sulfoximine had no effect on doxorubicin sensitivity in either subline. Thus, it appears that GSH-based detoxification systems are not causally involved in maintaining the MDR phenotype in 8226 human myeloma cells; rather they appear to comprise an epiphenomenon associated with the resistance selection procedure. PMID- 2930578 TI - Ability of 1-methyltetrazole-5-thiol with microsomal activation to inhibit aldehyde dehydrogenase. AB - Antibiotics that contain the 1-methyltetrazole-5-thiol (MTT) leaving group are associated with an adverse effect when alcohol is ingested after their administration. Therefore, the ability of MTT to inhibit an enzyme in alcohol metabolism, aldehyde dehydrogenase (ALDH), was examined. In the absence of microsomes, MTT did not inhibit ALDH obtained from either yeast or rat liver. In the presence of rat hepatic microsomes, MTT was able to inhibit the enzyme from both sources. The characteristics of the inhibition were studied, using the yeast enzyme, and found to be dependent upon the length of incubation with the hepatic microsomes and upon the concentration of MTT. Inhibition required the presence of NADH and was not detected if the microsomes were heat treated. Dilution did not reverse the inhibition. Intact antibiotics which contain the MTT moiety did not cause an inhibition of yeast ALDH unless the antibiotics were first treated with potassium hydroxide and then incubated with microsomes. Inhibition of ALDH activity measured in the mitochondrial plus microsomal fractions of rat liver also required NADH and was prevented by glutathione and heat treatment of the microsomes. These results indicate that microsomal activation of MTT is necessary for inhibition of aldehyde dehydrogenase. The behavior of MTT described here may explain the adverse effect observed if alcohol is ingested following administration of MTT-containing antibiotics. PMID- 2930580 TI - Oxidative and mitochondrial toxic effects of cephalosporin antibiotics in the kidney. A comparative study of cephaloridine and cephaloglycin. AB - Cephaloridine and cephaloglycin are the two most nephrotoxic cephalosporins released for human use. Cephaloridine has been shown to produce both oxidative and mitochondrial respiratory injury in renal cortex in patterns of dose (or concentration) and time that are consistent with pathogenicity. Cephaloglycin also produces respiratory toxicity, and recent studies have provided evidence that this injury results from an inactivation of mitochondrial anionic substrate transporters. The abilities of cephaloglycin to produce oxidative changes and cephaloridine to block mitochondrial substrate uptake have not been examined yet. We therefore compared these two cephalosporins with one another and with cephalexin, which is not nephrotoxic, in the production of the following: (1) several components of oxidative stress or damage [depletion of reduced glutathione (GSH) and production of oxidized glutathione (GSSG) in renal cortex, inhibition of glutathione reductase in vitro, and production of the lipid peroxidation products malondialdehyde (MDA) and conjugated dienes (CDs) in renal cortex]; and (2) renal cortical mitochondrial toxicity [to both respiration with, and the transport of, succinate]. Cephaloridine depleted GSH and elevated GSSG in renal cortex, inhibited glutathione reductase, and increased both MDA in whole cortex and CDs in cortical microsomes and mitochondria. While cephaloglycin depleted GSH at least as much as did cephaloridine, it produced one-fifth as much GSSG and had little or no effect on glutathione reductase activity or on cortical MDA or microsomal CDs; cephaloglycin caused a transient small increase of mitochondrial CDs. Cephalexin produced no oxidative changes except for a slight increase of mitochondrial CDs comparable to that produced by cephaloglycin. Both cephaloridine and cephaloglycin, but not cephalexin, decreased the unidirectional uptake of, and respiration with, succinate in cortical mitochondria. We conclude that cephaloridine and cephaloglycin are both toxic to mitochondrial substrate uptake and respiration, but differ significantly in their generation of products of oxidation. PMID- 2930581 TI - Effects of clofibrate and acetylsalicylic acid on hepatic carnitine palmitoyltransferase synthesis. AB - Clofibrate and acetylsalicylic and have both been reported to increase carnitine palmitoyltransferase (CPT) activity when administered to rats. The purpose of the present study was to determine the mechanism of the increase in CPT activity. Rats (150-200 g) were fed one of the following: chow, chow with 0.5% clofibrate, or chow with 1% acetylsalicylic acid for 2 weeks. At the end of this time, hepatic CPT activity was increased 4-fold over control in the clofibrate group and 3.6-fold over control in the acetylsalicylic acid group. Immunoreactive protein increased 4.0- and 3.6-fold, respectively, over control. Transcription rates of hepatic nuclei were increased 2.8- and 1.9-fold over control in the clofibrate and acetylsalicylic acid groups, and hepatic mRNA levels increased 2.8 and 2.0-fold respectively. These data indicate that increases in CPT activity caused by clofibrate and acetylsalicylic acid administration are due, at least in part, to increased CPT protein, resulting from increased transcription rate and levels of mRNA specific for CPT. PMID- 2930582 TI - Effects of the nonsteroidal anti-inflammatory drug mefenamic acid on energy metabolism in the perfused rat liver. AB - The action of mefenamic acid, a nonsteroidal anti-inflammatory drug, on energy metabolism in the isolated perfused rat liver was investigated. Mefenamic acid in the range between 0.1 and 1.0 mM was infused to livers from well-fed rats and from 24-hr fasted rats. The former were perfused with substrate-free Krebs/Henseleit-bicarbonate buffer, allowing the measurement of glycogenolysis and glycolysis from endogenous glycogen. The livers from 24-hr fasted rats, on the other hand, were perfused with Krebs/Henseleit-bicarbonate buffer containing fructose, thus allowing the measurement of fructolysis and glucose synthesis. Oxygen consumption was measured in both cases. When present in the range between 0.1 and 0.5 mM, mefenamic acid increased glycolysis, oxygen uptake, glycogenolysis and fructolysis. Higher concentrations, depending on the perfusion conditions, were inhibitory. Glucose production from exogenous fructose, on the other hand, was inhibited at low mefenamic acid concentrations. In general terms, the effects of mefenamic acid on energy metabolism seemed to be the primary consequence of its uncoupling action on the respiratory chain. This conclusion is supported mainly by the opposite effects on glucose synthesis (inhibition) and oxygen consumption (activation). The intracellular concentration of mefenamic acid is much higher than the extracellular one, a phenomenon which may represent binding to intracellular membrane or proteins. PMID- 2930583 TI - Nimodipine reduces postischemic lactate levels in the isolated perfused rat brain. PMID- 2930584 TI - Amrinone potentiates catecholamine-induced lipolysis in fat cells. PMID- 2930585 TI - Extraction of AZT and dideoxynucleosides by rat prostate but not testis. PMID- 2930586 TI - Inducibility of rat liver cytochrome P-450IA1 (P-450c) mRNA during the partial inhibition of protein synthesis. PMID- 2930587 TI - Intestinal first-pass metabolism of phenacetin in rabbits pretreated orally and intraperitoneally with 3,4-benzpyrene. PMID- 2930588 TI - 5-Chloro-substituted derivatives of 2', 3'-didehydro-2',3'-dideoxyuridine, 3' fluoro-2',3'-dideoxyuridine and 3'-azido-2',3'-dideoxyuridine as anti-HIV agents. PMID- 2930589 TI - Activity of N-(2-hydroxypropyl)methacrylamide copolymers containing daunomycin against a rat tumour model. PMID- 2930590 TI - Microsomal and cytosolic epoxide hydrolase and glutathione S-transferase activities in the gill, liver, and kidney of the rainbow trout, Salmo gairdneri. Baseline levels and optimization of assay conditions. AB - Microsomal and cytosolic epoxide hydrolase (mEH and cEH respectively) and glutathione S-transferase (GST) activities were measured in the liver, kidney, and gills of rainbow trout. Assays were optimized for time, pH, and temperature, using trans-stilbene oxide (TSO) and cis-stilbene oxide (CSO) as substrates for cEH and mEH, respectively. Optimal pH values for mEH, cEH, and GST were similar to mammalian values (i.e. 8.5, 7.5, and 9). Temperature optima differed between tissues and cell fractions. Specific activity of cEH-TSO was 3-14 times greater than mEH-CSO for all three tissues, and 8-60 times greater on a tissue weight basis. Liver and, to a lesser extent, kidney mEH were active against benzo[a]pyrene 4,5-oxide, whereas gill mEH was not active against this substrate. Liver cytosolic GST was active against CSO and 1-chloro-2,4-dinitrobenzene (CDNB) but not TSO, whereas gill and kidney cytosolic GST were active only against CDNB. Liver and kidney microsomal GST were active against CDNB, but no activity was found in gill microsomes. The results are discussed in relation to possible endogenous substrates and uninduced xenobiotic metabolizing capacities of different trout tissues. PMID- 2930591 TI - Direct inhibition of contractile apparatus by analogues of amiloride in the smooth muscle of guinea-pig taenia caecum and chicken gizzard. AB - The relaxant effects of amiloride and its analogues, benzamil, 5-(N,N-diethyl) amiloride (DEAM) and 5-(N-ethyl-N-isopropyl)-amiloride (EIAM), were investigated using smooth muscle of guinea-pig taenia caeci and chicken gizzard. High K+ induced contractions of intact taenia and gizzard were inhibited by these compounds (1-100 microM) with the order of potency; benzamil greater than or equal to EIAM greater than DEAM greater than amiloride. Contractions of permealized taenia and gizzard were also inhibited by these compounds at concentrations 8-35 times higher than those needed to inhibit the contractions of intact tissues. These compounds inhibited 20 K myosin light chain (MLC) phosphorylation at the concentrations needed to inhibit the contraction in the permealized muscles. Calmodulin (CaM) activity, as monitored by erythrocyte membrane (Ca2+ + Mg2+)-ATPase and phosphodiesterase activities, was inhibited by DEAM and EIAM at similar concentrations as those to inhibit the MLC phosphorylation. Benzamil also inhibited CaM activity at concentrations 4-8 times higher than those required to inhibit MLC phosphorylation. However, amiloride failed to inhibit CaM activity. Among these compounds, amiloride and benzamil inhibited Ca2+/CaM-independent MLC phosphorylation due to trypsin-treated MLC kinase. Taenia tissue gradually accumulated these compounds and the tissue/medium ratio exceeded 3.5-17 after a 3-hr incubation period. These results indicate that amiloride and its analogues inhibit smooth muscle contraction mainly by the direct inhibition of MLC phosphorylation. The inhibitory effect of amiloride may be attributable to the inhibition of MLC kinase, whereas the inhibitory effect of DEAM and EIAM may largely be attributable to the inhibition of CaM. Benzamil may inhibit contraction by the inhibition of both MLC kinase and CaM. Differences in the drug-sensitivity between intact and permealized tissues may be attributable to the difference in drug accumulation by the cell. PMID- 2930592 TI - The alkylation of DNA in vitro by 2,5-bis(2-hydroxyethylamino)-3,6-diaziridinyl 1,4-benzoquinone (BZQ)--I. AB - Cell toxicity by BZQ could not be explained by free radical formation and thus further work has been undertaken to elucidate a possible mechanism of cell killing. By using radiolabelled BZQ, in vitro DNA-drug binding has been investigated. The effect of salt, buffer and drug concentrations was determined in the pH range 4.0 to 8.0. The influence of in situ oxidation and reduction on BZQ binding was also studied as a function of pH. In an effort to ascertain any base specificity of BZQ binding the homopolymers, Poly[dG]. Poly[dC] and Poly[dA]. Poly[dT] were treated with radiolabelled BZQ in the pH range 4.0 to 8.0. A fluorescence assay was used to demonstrate the possible involvement of DNA cross-linking in cellular activity. From this work, it was concluded that BZQ functions as a bifunctional alkylating agent by an acid-assisted aziridine ring opening mechanism and that other factors including oxidation or reduction are much less important. PMID- 2930593 TI - Inhibition of the hepatic O6-alkylguanine-DNA alkyltransferase in vivo by pretreatment with antineoplastic agents. AB - The mammalian DNA repair enzyme O6-alkylguanine-DNA alkyltransferase (AT) is inactivated during the repair process and its activity can only be restored by de novo synthesis. We have made use of this property to determine whether and to what extent various chemotherapeutic agents alkylate DNA in the O6-position of guanine, ie. produce lesions susceptible to AT repair. Adult female Fischer rats received a single i.p. injection of a high dose (LD50) of the respective agent and, 5 hr later, a chasing dose of N-nitroso-[14C]dimethylamine (0.2 mg/kg; 4 hr survival). The amount of 7-[14C]methylguanine formed was approximately 95 mumol/mol guanine and not significantly altered by pretreatment with any of the drugs. The ratio of O6-[14C]methylguanine/7-[14C]methylguanine was 0.019 for control animals, indicating that during the observation period of 4 hr, 83% of the O6-[14C]methylguanine produced had been removed by the hepatic AT. Little or no effect was found in rats that received spirohydantoin mustard, hexamethylmelamine, cis-platinum or mitomycin C. A significant increase in the O6 /7-[14C]methylguanine ratio was found after pretreatment with AZQ (0.026) and cyclophosphamide (0.028), agents for which lesions involving the O6-position of guanine have not yet been identified. N-(2-Hydroxyethyl)-N-nitrosourea and the cytostatic haloethylinitrosoureas, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), 1 (2-chloroethyl)-3-(2,6-dioxo-3-piperidyl)-1-nitrosourea (PCNU), and N-chloroethyl N-hydroxyethylnitrosourea (HECNU) inhibited the hepatic AT, producing a ratio of 0.025-0.035. Considerably higher ratios of 0.059 and 0.101 were observed after administration of the methylating agents procarbazine and 5-(3,3-dimethyl-1 triazeno)imidazole-4-carboxamide (DTIC), respectively. Complete saturation of the repair system (O6-/7-[14C]methylguanine ratio, 0.11) was only achieved with N methyl-N-nitrosourea. PMID- 2930594 TI - Mutagenicity of benzyl S-haloalkyl and S-haloalkenyl sulfides in the Ames-test. AB - The mutagenicity of benzyl 1,2,3,4,4-pentachlorobutadienyl sulfide (BPBS) and benzyl 1,2-dichlorovinyl sulfide (BDVS) was studied in the Ames preincubation assay to investigate the hypothesis that the mutagenic effect of the cysteine S conjugates S-(pentachlorobutadienyl)-L-cysteine and S-(1,2-dichlorovinyl)-L cysteine is associated with their metabolism to unstable thiols. Under conditions enabling cytochrome P-450-dependent benzylic hydroxylation of BPBS and BDVS, both benzyl sulfides were mutagenic. These results in combination with the lack of mutagenicity observed with benzaldehyde and with the tert-butyl analogues, which cannot be metabolized to a hemimercaptal, indicate that the formation of unstable thiols is responsible for the mutagenic effects of the benzyl sulfides and the corresponding cysteine S-conjugates. Benzyl 2-chloro-1,1,2-trifluoroethyl sulfide, which also undergoes benzylic hydroxylation, was negative in the Ames Test; this is in agreement with the observed lack of mutagenicity of the corresponding S-conjugate S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine. Also, benzyl 2-chloroethyl sulfide, which, along with the corresponding S-conjugate S (2-chloroethyl)-L-cysteine, does not require bioactivation, was a potent, direct acting mutagen in the Ames-Test. PMID- 2930595 TI - Inhibitory effects of nilutamide, a new androgen receptor antagonist, on mouse and human liver cytochrome P-450. AB - The effects of nilutamide were studied first with human liver microsomes. At concentrations expected in the human liver (110 microM), nilutamide inhibited hexobarbital hydroxylase, benzphetamine N-demethylase, benzo(a)pyrene hydroxylase and 7-ethoxycoumarin O-deethylase activities by 85, 40, 35 and 25%, respectively. There was no in vitro inhibition of NADPH-cytochrome c reductase activity, no in vitro loss of CO-binding cytochrome P-450, and no spectral evidence for the in vitro formation of a possible cytochrome P-450Fe(II)-nitroso metabolite complex. Other studies were performed with mouse liver microsomes. Nilutamide (550 microM) did not significantly increase the consumption of NADPH by aerobic microsomes, and did not modify the kinetics for the reduction of cytochrome P-450 by NADPH cytochrome P-450 reductase in an anaerobic system. Nilutamide (22 microM) produced either a type I or a type II binding spectrum. Kinetics for the inhibition of hexobarbital hydroxylase were consistent with competitive inhibition. A last series of experiments was performed after administration of nilutamide in mice. Thirty minutes after administration of doses (15 or 30 mumol.kg-1 i.p.) similar to those used in humans, the hexobarbital sleeping time was increased by 40 and 60%, respectively. There was no evidence, however, for the irreversible inactivation of microsomal enzymes since CO-binding cytochrome P 450 and monooxygenase activities remained unchanged in liver microsomes from mice killed 1 or 6 hr after administration of nilutamide (30 mumol.kg-1 i.p.). These results show that nilutamide inhibits hepatic cytochrome P-450 activity, and suggest that inhibition may actually occur after therapeutic doses of nilutamide in humans. PMID- 2930596 TI - Effects of 15(S)-15-methyl prostaglandin E2 methyl ester on phospholipid metabolism in rat gastric mucosa. AB - The effects of 15(S)-15-methyl prostaglandin E2 (PGE2) methyl ester on gastric mucosal metabolism of phospholipids in intact rats and rats injured by intragastric instillation of acidified taurocholic acid were examined by using radioisotope-labeled precursors. The incorporation of palmitic, oleic and arachidonic acids into phosphatidylcholine (PC) and phosphatidylethanolamine (PE) was reduced by treatment with 15(S)-15-methyl PGE2 methyl ester in the intact rats, but the incorporation of glycerol was unaffected or affected only slightly. Instillation of acidified taurocholic acid resulted in decreased incorporation of palmitic acid and glycerol into PC and PE, whereas pretreatment with 15(S)-15 methyl PGE2 methyl ester caused the incorporations of these precursors to be maintained after acidified taurocholic acid treatment. These results suggest that 15(S)-15-methyl PGE2 methyl ester may reduce the incorporation of fatty acids into PC and PE by inhibition of the deacylation-reacylation cycle either directly or indirectly, whereas acidified taurocholic acid decreases de novo synthesis of PC and PE, and probably also the reacylation of fatty acid into phospholipids. Pretreatment with 15(S)-15-methyl PGE2 methyl ester protected the PC- and PE synthesizing activity against the injury induced by acidified taurocholic acid, and this effect may be involved in the prevention of mucosal damage. PMID- 2930597 TI - In vivo and in vitro studies of the hepatotoxic effects of 4-chlorophenol in mice. AB - 4-Chlorophenol (4-CP) was studied for its toxicological effect on liver by using both in vivo and in vitro approaches. Male mice were administered 4-CP, 1.5 mmol/kg body weight, i.p., and were killed at 10, 20, 30 and 50 min after drug injection. Either i.p. or oral 4-CP administration significantly lowered total liver thiol levels by 20-30% after 30 min and 3 hr respectively. This time dependent effect of 4-CP after i.p. treatment was enhanced when mice were pretreated with hepatic microsomal enzyme inducers (phenobarbital, 40 mg/kg body weight, b.i.d., 7 days; and beta-naphthoflavone, 80 mg/kg body weight once daily, 4 days). Further, the microsomal cytochrome P-450 inhibitor, SKF 525-A, 75 mg/kg body weight injected i.p. to mice 30 min prior to 4-CP administration, blocked the reduction of liver thiol content produced by 4-CP. The results suggest that a chemically reactive intermediate of 4-CP may be formed in liver which is responsible for the observed decrease in liver thiol content. Other investigations were done to characterize the in vitro irreversible binding of [14C]4-CP. [14C]4-CP was bound irreversibly to mouse liver microsomal proteins in a concentration-dependent manner. Binding was NADPH dependent and gave a maximal binding of 12.0 nmol/mg protein/20 min and an apparent binding constant of 0.222 mM. [14C]-Binding of 4-CP was increased by 155 and 127% in liver microsomes of phenobarbital- and beta-naphthoflavone. SKF 525-A, and CO:O2 (4:1, v/v)] and selected nucleophilic compounds (glutathione, L-cysteine or L-lysine) significantly reduced [14C]4-CP binding to mouse liver microsomes. An epoxide hydrolase inhibitor, cyclohexene oxide, did not alter the extent of irreversible binding, whereas scavengers of superoxide anions or agents that are reported to reduce accumulation of active semiquinone and quinone species (L-ascorbic acid, superoxide dismutase or epinephrine) decreased the binding of [14C]4-CP to mouse liver microsomal proteins by 56, 31 and 92% respectively. The data suggest that semiquinone and quinone species of 4-CP may be the chemically reactive intermediates leading to the in vivo reduction of liver thiol levels. Since 4-CP is a minor contaminant and possible metabolite of clofibrate and chemically related hypolipidemic agents, 4-CP and its metabolites may be partly responsible for some of the hepatotoxic effects seen after long-term administration of this therapeutic class of drugs. PMID- 2930598 TI - Acute hydrogen sulfide poisoning. Demonstration of selective uptake of sulfide by the brainstem by measurement of brain sulfide levels. AB - The possibility of measuring sulfide levels in the central nervous system (CNS) opens up many avenues for exploration. In acute hydrogen sulfide (H2S) poisoning, death results from loss of central respiratory drive. To date, however, measurement of brain sulfide has not been possible. By employing gas dialysis and ion chromatography coupled to electrochemical detection, rat brain sulfide levels could be measured either following inhalation of H2S or after injection of sodium hydrosulfide (median lethal dose, [LD50] = 14.6 +/- 1.00 mg/kg). Accumulation of brain sulfide was linearly proportional to the dose over the range 0.50 LD50 to 3.33 LD50 units, and was strongly correlated with mortality data (R = 0.947). Furthermore, analysis of untreated (control) brain showed an endogenous sulfide level of 1.57 +/- 0.04 micrograms/g (mean +/- SE; N = 16). Studies on various rat brain regions (brainstem, cerebellum, hippocampus, striatum and cortex) showed that the endogenous sulfide level of brainstem, 1.23 +/- 0.06 micrograms/g, was significantly lower than that of the other brain regions. Net uptake of sulfide was greatest in the brainstem (3.02 micrograms/g) compared to the other regions as was the selective accumulation of sulfide as calculated from normalized blood flow rates. The results of subcellular fractionation demonstrated that sulfide was detectable in fractions enriched in myelin, synaptosomes and mitochondria. Approximately one-quarter of the endogenous sulfide content of whole rat brain was found in the mitochondrial fraction. The sulfide content of these fractions increased 2- to 3-fold after 50 mg/kg NaHS, the greatest increases occurring in myelin- and mitochondrial-enriched fractions. PMID- 2930599 TI - Mutant fibronectin gene in skin fibroblasts of sclerotic lesions from patients with progressive systemic sclerosis. AB - A mutant fibronectin gene was identified in skin fibroblasts obtained from sclerotic lesions of 7 patients with progressive systemic sclerosis. We found 2 point mutations adjacent to the cell-attachment tetrapeptide DNA sequence in the cell-binding domain of the fibronectin gene. This observation suggests that the mutant fibronectin is related to an integral component of sclerotic pathogenesis through abnormal cellular interactions. PMID- 2930600 TI - Class II major histocompatibility complex gene sequences in rheumatoid arthritis. The third diversity regions of both DR beta 1 genes in two DR1, DRw10-positive individuals specify the same inferred amino acid sequence as the DR beta 1 and DR beta 2 genes of a DR4 (Dw14) haplotype. AB - The DR1 and DRw10 beta 1 chain genes were isolated from each of 2 individuals with rheumatoid arthritis who were heterozygous for these class II major histocompatibility complex specificities. The sequences of the DR1 beta 1 chains from both patients were identical, differing from previously reported DR beta 1 chains of individuals without RA by 2 amino acid substitutions, at positions 85 (Val-Ala) and 86 (Gly-Val), and by a silent mutation at the last nucleotide of codon 78 (C-T), resulting in the loss of a Pst I restriction endonuclease site. Identical DRw10 beta 1 chain genes were found in both patients. These were shown to encode the epitope recognized by monoclonal antibody 109d6. This antibody also recognizes an epitope on the DRw53 beta 2 chain of the DR4 haplotype. The third diversity regions of the DR1 beta (amino acids 67-74) and the DRw10 beta 1 chains (amino acids 67-73) were identical, respectively, with those of the DR4 (Dw14) beta 1 and beta 2 chains, raising the possibility that in these patients, the third diversity regions of the two DR beta 1 chain genes present in trans are conformationally equivalent to the cis-encoded third diversity regions of the DR4 (Dw14), DR beta 1, and beta 2 chains. The nucleotide sequences of the DQ beta complementary DNA clones were identical to that of the DQw1 beta chain, and no DR beta 2 complementary DNA clones were identified. PMID- 2930601 TI - Expression of the major rheumatoid factor cross-reactive idiotype in juvenile rheumatoid arthritis. AB - The major rheumatoid factor cross-reactive idiotype (RF-CRI), defined by prototypic monoclonal IgM rheumatoid factors, is expressed in high frequency by pokeweed mitogen-derived plasma cells from patients with rheumatoid arthritis who express RF in their sera. Unlike adults with rheumatoid arthritis, most patients with juvenile rheumatoid arthritis are seronegative for RF, as detected by classic IgG binding assays. We report that approximately 50% of seronegative patients with juvenile rheumatoid arthritis express the RF-CRI in high frequency among their pokeweed mitogen-derived plasma cells, and that approximately 33% of patients express the RF-CRI in high titer in their sera. The possible mechanisms for expression of an idiotypic marker of RF without expression of IgG binding activity by classic assays are discussed. PMID- 2930602 TI - Is it mandatory to examine synovial fluids promptly after arthrocentesis? AB - Fifty synovial fluid (SF) samples from patients with various types of arthritis were examined promptly after joint aspiration and after storage at room temperature (22 degrees C) or at refrigerator temperature (4 degrees C) for 1 hour, 2 hours, 3 hours, 6 hours, 1 day, and 3 days, then weekly for 3 weeks and monthly for 2 months. We found that the leukocyte count (white blood cell [WBC] count) decreased within a few hours. In 4 SF samples from patients with mild inflammation (initial range 3,150-6,200 WBC/mm3), the WBC count decreased into a "noninflammatory" range (less than 2,000/mm3) within 5-6 hours. In 3 of 5 SF samples that on the first day were found to be laden with crystals of calcium pyrophosphate dihydrate (CPPD), the crystals were much less abundant and were difficult to recognize by the next day. CPPD crystals dissolved completely in all SF samples by 3-8 weeks of the study. Monosodium urate crystals remained detectable throughout the 8 weeks of study, but they became smaller, less birefringent, and less numerous with time. Clumps of apatite-like crystals persisted for several months. Most SF samples initially negative for apatite-like crystals remained negative over time. New, artifactual crystals, including alizarin red S-positive clumps or star-shaped arrays, plate-like structures, positively birefringent Maltese crosses, and hematoidin crystals, developed with time. Because of these observations, we urge prompt examination of SF specimens to avoid the problems of misdiagnosing borderline inflammatory fluids, missing CPPD crystals that dissolve with time, or over-interpreting the findings because of the new, artifactual crystals. PMID- 2930603 TI - Panner's disease. PMID- 2930604 TI - Microheterogeneity of alpha 1-acid glycoprotein in the detection of intercurrent infection in patients with rheumatoid arthritis. AB - We evaluated the clinical usefulness of determinations of alpha 1-acid glycoprotein (AGP) microheterogeneity in distinguishing patients who have active rheumatoid arthritis (RA) from those who have RA and an intercurrent infection. AGP microheterogeneity was studied by affinity electrophoresis with concanavalin A as the ligand, and the results were expressed as reactivity coefficients (RC). Significant differences were found between the mean RC (+/- SD) in healthy individuals (1.27 +/- 0.16) and the mean RC in RA patients with intercurrent infection (1.74 +/- 0.90), as well as with the mean RC in RA patients with grades III and IV disease activity (0.92 +/- 0.18 and 0.81 +/- 0.25, respectively). Moreover, an additional microheterogeneous form of AGP, similar to that observed in non-RA patients with infections, was noted in RA patients with infections (sensitivity 100%, specificity 100%). The results show that an increase in AGP reactivity with concanavalin A is a sensitive indicator of intercurrent infection in patients with RA. PMID- 2930605 TI - Factitious septic arthritis. AB - Septic arthritis is an uncommon manifestation of factitious illness. We report 2 patients who developed septic arthritis of the knee after repeated self administered intraarticular injections. Multiple unusual infective agents were isolated. These cases illustrate malingering and Munchausen syndrome, 2 examples from the spectrum of factitious disease syndromes. PMID- 2930606 TI - Large granular lymphocytes and neutropenia in a patient with ankylosing spondylitis. PMID- 2930607 TI - Alpha-methyldopa-induced systemic vasculitis confused with Wegener's granulomatosis. PMID- 2930608 TI - The role of cholesterol-lowering agents in drug-induced rhabdomyolysis and polymyositis. PMID- 2930609 TI - Comment on the article by Downey et al. PMID- 2930610 TI - Standard abbreviations for antiphospholipid antibodies. PMID- 2930613 TI - Low density lipoprotein interaction with artery derived proteoglycan: the influence of LDL particle size and the relationship to atherosclerosis susceptibility. AB - An in vitro binding system was used to determine whether increases in LDL particle size and altered LDL chemical composition accompanying increased plasma cholesterol concentrations result in greater association of LDL with artery proteoglycan (PG) and whether the binding is related to atherosclerosis. LDL isolated from hypercholesterolemic atherosclerosis-susceptible White Carneau and resistant Show Racer pigeons was complexed to purified White Carneau pigeon aorta derived high molecular weight PG under conditions whereby PG monomers were saturated. Using LDL of molecular weight greater than 5.0 x 10(6) daltons from both pigeon breeds, an inverse correlation between LDL size and the number of LDL particles bound per micrograms PG was demonstrated (r = 0.87, P less than 0.01). This relationship was attributed to the increased size of the LDL particle rather than any modification in chemical composition known to occur when LDL size increases, suggesting the major effect was attributed to steric hindrance. White Carneau pigeons with high molecular weight LDL had more severe atherosclerosis and the PG-LDL complexes contained excess cholesterol but no relationship was seen between atherosclerosis and number of LDL complexed. In animals with LDL between 3.6 x 10(6) and 4.8 x 10(6) daltons, considerable variability in PG binding was apparent, but this also was not related to LDL chemical composition. In this group of pigeons, which were all White Carneau, the positive relationship of PG-LDL binding and aorta cholesterol concentration was significant (r = 0.67, P less than 0.05). These results suggest that factors other than chemical composition (perhaps surface charge or apoprotein conformation changes) influence PG-LDL binding and that the assessment of PG-LDL binding is useful in predicting atherosclerosis in animals that do not respond to hypercholesterolemia by increasing LDL size. PMID- 2930612 TI - Spontaneous injuries in the aortic endothelium of the inherited cataract rats and their prevention by tocopherol. A study by scanning electron microscopy. AB - The aortic endothelium of inherited cataract rats (ICR), which spontaneously develop cataracts and neutrophilia, was examined by scanning electron microscopy using silver nitrate staining and pressure fixation. In ICR aged 4 weeks, the luminal surface of the aorta was similar to that in Wistar rats from which they had been derived. However, 8 weeks after birth, endothelial cells were upraised and partially detached from an underlying tissue. At 16 weeks, morphological changes exhibited by such detaching cells were more evident than at 8 weeks and fibrin was seen to be adhering to the surface of these cells; no platelet involvement was noted, however. Oral administration of DL-alpha-tocopheryl acetate for 2 weeks resulted in a reduction in the extent of endothelial injury and the luminal surface of the aorta became similar to that seen in 4- or 8-week old animals. We found that the number of age-associated spontaneous injuries occurring in the aortic endothelium of ICR could be reduced by tocopherol administration. PMID- 2930611 TI - Reduction of plasma lipid and homocysteine levels by pyridoxine, folate, cobalamin, choline, riboflavin, and troxerutin in atherosclerosis. AB - Elevated plasma homocysteine and lipid levels are risk factors for atherosclerosis. The plasma levels of homocysteine, determined in acid hydrolyzates of plasma, were found to be correlated with total cholesterol (r = 0.47, P less than 0.001), triglycerides (r = 0.40, P less than 0.01), and body mass index (r = 0.42, P less than 0.01) in 52 males, aged 30-60. A group of 12 male survivors of acute myocardial infarction was given pyridoxine, folate, cobalamin, choline, riboflavin, and troxerutin for 21 days. The plasma concentrations of homocysteine and alpha-amino adipic acid declined to 68% (P less than 0.001) and 57% (P less than 0.001) of the pretreatment values, and the cholesterol, triglycerides, and LDL apo B declined to 79% (P less than 0.001), 68% (P less than 0.01), and 63% (P less than 0.001) of the pretreatment values, respectively. The results suggest a new strategy for control of the metabolic abnormalities in atherosclerosis through the use of naturally occurring, non toxic nutrients which minimize homocysteine accumulation. PMID- 2930614 TI - Effect of exercise training on plasma cholesterol and cholesterol kinetics in adult female rats. AB - Adult female rats fed laboratory chow of low cholesterol content were trained by swimming for 77 days. Plasma cholesterol concentration decreased 38% compared to sedentary controls. Whole body cholesterol metabolism was studied by injection of [14C]cholesterol tracer and determination of the plasma cholesterol-specific activity during the last 49 days of the experiment. The rate constant for elimination of cholesterol from the body was 31% higher in swimming than in sedentary animals, and the size of the rapidly-exchanging cholesterol pool was 28% smaller. These results suggest that enhanced cholesterol excretion or catabolism accompanies exercise training in the rat. PMID- 2930615 TI - Apolipoprotein A-I inhibits transformation of high density lipoprotein subpopulations during incubation of human plasma. AB - We have examined the effect of added apolipoprotein A-I (apoA-I) on the changes in high density lipoprotein (HDL) particle size that occur when human plasma is incubated in vitro. In the absence of added apoA-I, incubation of plasma at 37 degrees C resulted in a dramatic increase in HDL particle size. When these incubations contained an inhibitor of LCAT, an additional population of smaller HDL particles was formed. These changes in particle size were even more pronounced when the incubations were supplemented with an artificial triglyceride emulsion, Intralipid. All these changes in HDL particle size were markedly inhibited when incubations were supplemented with apoA-I. Even when the amount of added apoA-I was as little as 4.5% of the endogenous apolipoprotein there was an obvious inhibition of the changes in HDL particle size. The presence of added apoA-I sufficient to increase the plasma concentration by 18% virtually abolished the changes in HDL particle size. This effect did not relate to an inhibition of cholesterol esterification, nor did it appear to depend on an incorporation of the added apoA-I into the HDL. PMID- 2930616 TI - Adhesion of leukocytes to the aortic endothelium of conventional, specific pathogen free (SPF) and hypercholesterolemic SPF rats. AB - Adhesion of leukocytes to the aortic endothelium was studied in specific pathogen free (SPF) and conventional rats and in SPF rats with diet-induced hypercholesterolemia. Nonspecific esterase activity with alpha-naphthyl acetate as substrate was used to characterize the adhered cells. Phagocytic activity was determined by injecting i.v. 0.1-0.4 ml/100 g doses of Monastral blue B (MbB). Adhesion in SPF rats was 8 +/- 4 esterase (+) cells/mm2. Adhesion in conventional rats was of the same order except in 2 cases with antibodies to Mycoplasma pulmonis and Kilham rat virus, where adhesion was 44 and 68 esterase (+) cells/mm2, respectively. For all MbB doses studied, phagocytic activity arose in a percentage of the adherent cells, ranging from 5 to 85%. Rats fed the hyperlipidic diet for 15 days developed severe hypercholesterolemia and adhesion was drastically increased to 200-700 esterase (+) cells/mm2. Results indicate that: (1) spontaneous pathology in rats may produce an increased adhesion of leukocytes to the endothelium, and (2) phagocytic activity is only expressed in a fraction of the esterase (+) cells adhered to the endothelium. PMID- 2930618 TI - Abstracts of papers. 38th annual scientific session of the American College of Cardiology. Anaheim, California, March 19-23, 1989. PMID- 2930617 TI - Lipids and endurance physical activity. PMID- 2930619 TI - Alcohol and traffic safety: a sensitivity analysis of data from composite sources. AB - Risk factors associated with single-vehicle driver fatalities are explored in a sensitivity analysis of data from composite sources. Information on fatalities was taken from the Federal Accident Reporting System data base for 1976-1981. Characteristics of the driving population were given by the 1973 National Roadside Breath Testing Survey (Wolfe 1974). Using Bayes theorem and logistic regression analysis, the effect of changing driver characteristics on the probability of a fatality was explored. The method used is proposed for a case control study in which the controls may not accurately represent the population from which the cases were drawn. Risk factors identified are generally in agreement with previous reports. PMID- 2930620 TI - Methods for assessing drivers' perception of specific hazards on the road. AB - The purpose of this research was to test a number of techniques for assessing drivers' perception of hazards. The techniques included three types of interview methods, the Q-sort method, and several variants of the repertory grid method. The techniques were judged largely on their ability to differentiate between old and young drivers, two groups with known differences in accident frequency. None of the interview techniques produced useful information regarding drivers' perception of hazards, and neither these techniques nor the Q-sort discriminated between old and young drivers. All the variants of the repertory grid differentiated between old and young drivers, in the sense that old drivers used extremes of the rating scale more often than young drivers. This phenomenon was most apparent with the fixed repertory grid. Further work on this technique revealed further differences between the age groups in terms of the correlational structure of the responses, which point to a number of hypotheses about risk perception in old and young drivers. PMID- 2930621 TI - Catastrophe modeling of the accident process: evaluation of an accident reduction program using the occupational hazards survey. AB - The report details a catastrophe theory model of the accident process with empirical validation. According to the cusp model, two distinct levels of risk can be observed for a distribution of group accident rates, one at 0.0 Occupational Safety and Health Association (OSHA)-reportable accidents per 100 person-years of exposure and one at 11.5. Changes within or between the two levels are determined by two control parameters: environmental hazard (asymmetry) and operator load (bifurcation). The sample consisted of 68 work groups from 8 Milwaukee-Chicago area sheet metal mills and foundries who completed the Occupational Hazards Survey (OHS). The OHS contributed six bifurcation variables (safety management, life stress, physical stress anxiety, beliefs about accident control, and experience) and two asymmetry variables (environmental hazards and danger). All organizations received an interpretive report of their survey responses with recommendations for accident control, and had held their reports for two to nine months at the time the follow-up accident rate data were collected. There were two additional bifurcation variables: months holding report and group size. Regression analysis determined that the cusp model (R2 = .42) was more than twice as accurate as the best log-linear or linear alternative. Accidents were successfully controlled by safety managers' attention to recommendations produced by the OHS analysis. Catastrophe theory provided some novel insights regarding the linkage between predictor variables and actual behavior. Research has shown that a substantial percentage of occupational accidents are the result of human error. In an effort to explain and predict such errors in a systematic manner, an accident process model based on the cusp catastrophe is developed and tested. The model offers several unique and useful properties: (1) It proposes that changes in accident rates for work groups are the result of a nonlinear dynamic process. (2) The distribution of accident rates is bimodal, with one model near zero and the other at some higher level. (3) Changes in accident rates are predicted from four sources: (i) ambient danger and hazard levels, (ii) variables that impact upon human performance capability, (iii) initial accident rates, and (iv) the mathematical function that interrelates those variables. (4) The mathematical model has inherent properties that allow for causal inference. Environmental and human performance factors can be operationalized as sets of more specific variables. In this application. The Occupational Hazards Survey was used to gather data from mill and foundry workers pertaining to hazards and dangers, adequacy of safety management, stress, anxiety, and beliefs about accident control.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2930622 TI - Matching fatal accident reporting system cases with National Center for Health Statistics motor vehicle deaths. AB - Motor vehicle traffic fatalities in the United States are described by two major data sources, the Fatal Accident Reporting System (FARS) and the National Center for Health Statistics Multiple Cause of Death data (NCHS). Certain data, such as the age and sex of the fatality, are reported by both sources. However, each source contains data absent from the other. For example, only the FARS describes the precise circumstances of injury, and only the NCHS identifies the anatomic injuries listed on the death certificate. Thus, it would be useful to have a single file that offers for each case all of the data provided in each of the separate files. Creation of such a file is impeded by the fact that neither file contains personal identifiers for the cases listed. The present paper describes a method of matching cases from the two files based on simultaneous agreement of several variables common to both files (age, sex, date of death, role in the crash, and state in which the injury occurred). Using this method, 85% of the FARS cases can be uniquely matched with a case in the NCHS data. PMID- 2930623 TI - Anthropomorphic dummy neck modeling and injury considerations. AB - This study investigates the modeling of the Hybrid III dummy head and neck system and its response under impulsive loading. Two neck models were proposed, one rigid, one flexible; both give satisfactory head kinematics upon comparing to minisled test results. The flexible neck model provides a more detailed understanding of the Hybrid III neck structure behavior. It indicates that the Hybrid III neck has a torque response similar to a human neck but has higher shear response. During flexion whiplash, the torque at the occipital condyle reverses its direction at about 25 ms after impact. Since concussion may be related to the head angular acceleration, which reaches its peak value in the first 25 ms, it might be necessary to extend the existing human torque-rotation corridor to include the neck response in this region. For flexion whiplash impact, simulation results indicated that the neck injury threshold is reached before exceeding the head injury threshold as the impact velocity is increased. PMID- 2930624 TI - A chimeric antibody with dual Fc regions (bisFabFc) prepared by manipulations at the IgG hinge. AB - A new chimeric antibody for therapeutic use in human cancer is described. First the derivative FabFc was prepared by linking Fab' gamma from monoclonal antibody to Fc gamma from human normal IgG1. The bismaleimide linking agent forms a thioether bond with an SH group released by reduction of SS bonds in the hinge of each constituent. It follows that one of the original two SS bonds in the Fc hinge still has both its S atoms free, and this bond is reformed by thiol disulphide interchange. The lone free SH in the Fc hinge can now be used to join two FabFc molecules through a similar bismaleimide linker to yield bisFabFc. As regards antibody activity against target cells, bisFabFc can be univalent, bivalent, or bispecific. Its juxtaposed dual Fc regions are designed to promote cooperative binding of effectors, and bisFabFc is indeed notably more powerful than its parent FabFc molecules in promoting complement lysis and antibody dependent cellular cytotoxicity. However it is not possible at present to distinguish the separate contributions of Fc architecture, antibody affinity and other factors towards this improvement. In the present state of development a variety of FabFc against a given neoplasm may be prepared in high yield from mouse IgG1 and IgG2a antibodies, and when convenient dimerized to bisFabFc in any combination of specificities. PMID- 2930625 TI - Pharmacological activities of spirogermanium and other structurally related azaspiranes: effects on tumor cell and macrophage functions. AB - Spirogermanium is a germanium containing azaspirane which has been shown to have activity in experimental models of cancer and immune dysfunction. A series of analogs of the parent compound were synthesized and evaluated in a number of in vitro and in vivo biological assays to define the structure-activity relationships of this class of compounds relative to their potential therapeutic activities. In a colony-forming assay using HT-29 human colon carcinoma cells various analogs in which carbon replaced germanium (e.g. carbon) retained the potent cytotoxic activity in vitro seen with spirogermanium. Increased cytotoxic potency within the group of carbon containing analogs was directly related to increase in the length of the alkyl group(s) attached to the carbon atom opposite the azaspirane ring structure. DNA and protein synthesis by HT-29 cells was inhibited by these compounds. However, inhibition occurred only at supralethal concentrations or after long exposure times with the drug. None of the azaspiranes demonstrated in vivo anti-tumor activity against P388 leukemia or ADJ PC6 plasmacytoma. The effect of these compounds on macrophage cell function was evaluated in vitro by their ability to modulate superoxide (O2-) production by macrophages. Spirogermanium inhibited the production of O2- by activated macrophages with an IC50 of 5 microM. Although macrophage viability did not appear to be decreased at the respective IC50 concentrations, the rank order potency for the analogs in the O2- production assay was directly proportional to that measured for their cytotoxic potency in the HT-29 colony formation assay. The results demonstrate that, within this class of compounds, (1) potent biological activity does not require the presence of germanium in the structure; (2) in vitro cytotoxic activity does not appear to be a direct result of the inhibition of macromolecular synthesis, and (3) macrophage function can be modulated in vitro at non-cytotoxic concentrations. These results are discussed in context with the reported anti-tumor activity of spirogermanium and the potential anti-arthritic and immunomodulatory activity of this class of compounds. PMID- 2930626 TI - Quinazoline antifolates inhibiting thymidylate synthase: computer modelling of the N10 substituent. AB - The synthesis and biological properties of N10-(2,2,2-trifluoroethyl)-5, 8 dideazafolic acid are described. It was fivefold less active as an inhibitor of L1210 thymidylate synthase (TS) than its N10-ethyl congener and sevenfold less active as an inhibitor of the growth of L1210 cells in culture. CNDO calculations were performed on the following N10 substituents in a model fragment of 5, 8 dideazafolic acid: propargyl, ethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, cyanomethyl and methyl. The resulting values of partial charge on the distal terminus of the substituent correlated with the TS inhibition induced by the substituent. In particular, the mildly net positive charge on the acetylenic hydrogen in the propargyl substituent (+0.064) was not matched by any other in the series. N10-propargyl-5, 8-dideazafolic acid continues as the best inhibitor in this series. PMID- 2930627 TI - Structural and biochemical comparison of the anti-mitotic agents colchicine, combretastatin A4 and amphethinile. AB - The novel agents amphethinile and combretastatin A4 are shown to be very similar to colchicine in their interactions with purified tubulin. All three agents can inhibit tubulin assembly at similar treatment levels and have comparable affinity constants for tubulin. Amphethinile and combretastatin A4 are capable of displacing colchicine but not vinblastine from tubulin. A comparison of the structures of these agents shows that whereas colchicine and combretastatin A4 contain a trimethoxybenzene group (a moiety also found in other colchicine-like agents such as podophyllotoxins and steganacin) no obvious similarity is seen for amphethinile. The three-dimensional structures of these agents, determined from either crystallographic data or by energy minimization procedures, show, however, that all three agents consist of two planar, or almost planar, ring systems which are tilted with respect to each other. Using computer graphic techniques it can be shown that their ring systems are superimposable and that the planar sections of each molecule are at an angle of 50-60 degrees to each other. It is proposed that the angular bicyclic structure of these agents is one determining factor for their efficient binding to tubulin. PMID- 2930628 TI - Nucleoside analogues: 7. Effect on colon, breast and lung tumours in mice of 5 fluorouracil/nitrosourea molecular combinations incorporating alkoxy and oxidized sulphur functions. AB - This study considers further changes in the carrier moiety of molecular combinations of the pyrimidine antimetabolite 5-fluorouracil (5-FU) and the alkylating group chloroethylnitrosourea (CNU). Detailed chemical syntheses are described of compounds incorporating (a) a simpler alkoxy group in the 'sugar' fragment, (b) attachment of the 5-FU residue to the C-X-C-C chain on the side of the heteroatom X distal from the CNU group, and (c) higher oxidation states of the sulphur atom in the prototypical compound B.3839. Anti-tumour activity of these analogues against a series of experimental murine colon, lung and mammary tumours is described. The pattern of activity reveals that the carrier moiety is important but further pharmacokinetics and metabolism studies are required to determine structure-activity relationships. PMID- 2930629 TI - Movement and novelty of a square wave display affect 2-deoxyglucose uptake in the rat visual system. AB - The [14C]2-deoxy-glucose (2-DG) autoradiographic technique revealed that movement and novelty of a visual display affected rat visual system metabolic activity. Hooded rats were monocularly tested in a surround consisting of patterns of black and white, horizontal and vertical, square wave gratings of different spatial frequencies. For one group this display remained immobile ('stationary' group), and for the other group the display intermittently rotated at 1.5 rpm ('moving' group). Each of these main groups was subdivided such that half had six sessions of prior exposure to the test display ('experienced' group) and half had no prior exposure ('novel' group). The movement groups showed relatively greater 2-DG uptake than the stationary groups in the superior colliculus and in the caudal lateral posterior nucleus, while the novel groups showed greater uptake than the experienced groups in visual cortex. PMID- 2930630 TI - Olfaction directs skilled forelimb reaching in the rat. AB - Rats were trained to reach for food pellets, which varied in size from 20 to 300 mg, from one of 21 locations on a shelf located just outside a test cage. After a barrier was lifted, giving access to a food pellet, latency to contact the food was timed, number of reaches to contact the food were counted, the distance of each misplaced reach from the food was measured and the success or failure of each attempt was noted. Control rats walked along the front of the cage sniffing to locate the food. Once they located a food pellet, they inserted their nose between the bars of the cage, sniffed the food for one to three respiratory cycles, raised their snout slightly, and then inserted a forepaw to grasp the food. They seldom required more than three reaches to contact the food and on about half of all trials they were successful in grasping the food. They were more successful in grasping medium-sized food pellets. Performance was unchanged on all measures after vision was occluded with eye patches. Following olfactory bulb removal, however, the rats no longer sniffed to locate the food or sniffed the food prior to initiating a reach. Rather they systematically moved along the length of the cage inserting their snout between the bars at each possible food location and without sniffing reached for the food 'as if blind'. Latency, number of reaches to contact the food and the distance of misplaced reaches increased whereas success rate remained unchanged. Substantial additional impairments were not produced when the bulbectomized rats were given visual occlusion. The study demonstrates that rats locate food and direct reaching using olfaction. The results are discussed in terms of the sensory control of skilled limb use and their relevance to the evolution of the sensory guidance of limb use. PMID- 2930631 TI - Reduction in anxiety after ejaculation in the rat. AB - The anxiety levels, tested in the conditioned defensive burying behaviour paradigm, were analyzed after various phases of copulatory behaviour. No differences in anxiety were found between the group of animals without sexual activity and the group of animals tested after five intromissions of the first ejaculatory series. A decrease in anxiety, reflected as a reduction in the burying behaviour, was found in the group of animals tested during the first and the second postejaculatory intervals or after two intromissions from the second series of copulation. The possible involvement of the GABAergic system mediating the reduction in anxiety during these phases of copulation is discussed. PMID- 2930632 TI - Dissociation of visual and olfactory conditioning in the neostriatum of rats. AB - In an experiment designed to demonstrate a double dissociation, the effects of bilateral electrolytic lesions of either the posteroventral or the ventrolateral regions of the neostriatum on the conditioned emotional response (CER) were examined. Posteroventral lesions impaired acquisition of the CER with a visual CS but not with an olfactory CS. Sham-operated posteroventral and ventrolateral lesioned animals acquired the visual CER normally. Ventrolateral lesions impaired acquisition of the CER with the olfactory CS but not with the visual CS. Sham operated ventrolateral and posteroventral lesioned animals acquired the olfactory CER normally. In a second experiment the effect of post-training unilateral intrastriatal microinjections of (+)-amphetamine on acquisition of the visual and olfactory CERs was studied. Posteroventral injections improved retention of the visual, but not the olfactory CER. Ventrolateral injections improved retention of the olfactory, but not the visual CER. Saline and delayed (+)-amphetamine injection controls demonstrated that the improvement of retention in each case was a retroactive improvement of memory for the recently acquired CERs by (+) amphetamine. These findings are consistent with previous reports of post-training memory facilitation mediated by dopaminergic function in the neostriatum. The results of both experiments are consistent with a regional functional heterogeneity hypothesis: the idea that anatomically linked areas of cortex and neostriatum process memories involving different stimuli in similar ways and that the integrity of these structures and their connections is necessary to establish and consolidate associative memory. PMID- 2930633 TI - Prefrontal cortex lesions attenuate substantia nigra self-stimulation: a reward summation analysis. AB - A curve-shift paradigm was used to assess the effects of lesions of the prefrontal cortex on self-stimulation from electrode sites in the substantia nigra. Combined lesions of the medial and sulcal cortical regions severely attenuated substantia nigra self-stimulation. These results are discussed in the context of the frontal cortex and the substantia nigra as belonging to a reinforcement system that is largely independent of the medial forebrain bundle system. PMID- 2930634 TI - Aging and sociosexual behavior in the male rat. AB - Senescent and young rats have been studied in a copulatory test and sociosexual approach test. The copulatory test was applied to investigate age-dependent changes in the copulatory capacity in the rat. The sociosexual approach test was used to describe motivational aspects of this behavior. Latencies, frequencies and durations of copulatory behaviors in the copulatory test and visits to various incentive animals in the approach test have been measured. Senescent rats had longer latencies and less frequencies of copulatory behaviors. In the approach test they showed less visits to the estrous female. Data were also subjected to a correlational analysis in order to relate the findings of the two tests. It is concluded that aged male rats differ from young ones in organizing their behavior in relation to time, are less social and have a less pronounced social preference pattern. In addition, the coherence between various elements of copulatory behavior was less in the senescent rat than in the young male rat, whereas the social approach patterns are more coherent in the aged male. PMID- 2930635 TI - Long-term deficits in water maze spatial conditional alternation performance following retrohippocampal lesions in rats. AB - The effects of large bilateral retrohippocampal lesions on long-term performance of conditional spatial alternation, incorporating a strong working memory component, were examined using a T-maze task motivated by swim-escape. The lesions, which included entorhinal cortex, subiculum, pre- and parasubiculum and invaded the molecular layer of the dentate gyrus, completely eliminated the previously acquired conditional alternation learning, and performance failed to recover with 40 days of testing. These findings support the contention that retrohippocampal structures are an important and necessary component of the neural circuitry mediating working memory. PMID- 2930636 TI - Behavioral responses to novelty and structural variation of the hippocampus in mice. I. Quantitative-genetic analysis of behavior in the open-field. AB - As a first step towards a multivariate quantitative-genetic analysis of covariations between heritable variation in hippocampal structure and mouse behavior, a univariate analysis of the genetic architecture of behavioral responses to novelty is presented. For several components of exploratory behavior considerable amounts of genetic variation were found and an evolutionary history of stabilizing selection for intermediate levels of exploration was inferred. Comparison of these results with those from a previous study indicated that even a relatively small diallel cross, involving 4-5 inbred strains, may provide useful genetic information on a specific sample of animals. Larger numbers of strains are needed to provide precise estimates of genetic parameters in a population. PMID- 2930637 TI - Behavioral responses to novelty and structural variation of the hippocampus in mice. II. Multivariate genetic analysis. AB - On the basis of results from lesion studies in rodents, covariations are expected to exist between naturally-occurring heritable variations in hippocampal morphology and exploratory behavior elicited by novel surroundings. For this reason, we set up a full diallel cross between five inbred mouse strains and analyzed the behavioral and the hippocampal anatomical variation in male animals from this cross. Employing a bivariate extension of the diallel-cross analysis, estimates were obtained for the phenotypical, environmental, and genetical correlations between the phenotypes studied. A factor analysis performed on the matrix of additive-genetic correlations revealed that variations in the size of the intra- and infrapyramidal mossy fiber terminal fields (iip-MF) are negatively related to open-field exploration and novelty-induced fear. These results indicate that having larger iip-MF projections promotes the collection and processing of information about a novel environment, entailing lower levels of exploration and fear. PMID- 2930638 TI - Differences in open-field behavior and in learning tasks between two rat strains differing in their reactivity to stressors. AB - The study characterizes differences between inbred Wistar-Kyoto (WKYs) and Brown Norway (BNs) rats in open-field behavior, and in discriminative learning and acquisition of an avoidance learning task. Hyper-reactivity of WKYs to novelty was demonstrated in an open-field test. Discriminative learning and retention thereof was slower in WKYs, but as efficient as in BNs. Acquisition of avoidance learning was also slower in WKYs, but their maximal avoidance score was much higher (approximately 85%) than in BNs. Also, recall of avoidance learning was slower for WKYs. We conclude: (1) hyper-reactivity of WKYs to novelty is expressed by their exceptional immobility and excess defecation in the open-field and is paralleled by their known hyper-reactivity to stressful stimuli, and (2) no strain differences exist in the ability to learn a discriminative task, but both acquisition and recall of an avoidance task are slower in WKYs. This may imply that the degree of reactivity to stressful environmental stimuli may play an important role in the acquisition of learning. PMID- 2930639 TI - Interaction of visual and non-visual signals in the initiation of smooth pursuit eye movements in primates. AB - The initiation of smooth pursuit eye movements (PEM) by visual and non-visual signals was analysed in humans and monkeys. While PEM latency ranged around 150 ms when a purely visual target was provided, it often dropped to about 0 ms, or even became negative, when target movement was coupled to the subject's arm; this suggests that signals about the intention to move the arm can be evaluated for PEM control. Eye movements always started in the visually correct direction, independent of the sign of coupling between arm and target; from this we conclude that intentional signals are not mere triggers, but also convey directional information. Short-latency PEM trials were intermixed with those characterized by normal latencies, which often resulted in bimodal latency distributions; this suggests that visual and intentional signals compete for the control of PEM. PMID- 2930640 TI - Rehabilitation nurses can do anything. PMID- 2930641 TI - Tibial nerve somatosensory evoked potentials in spinal cord hemisection. AB - Somatosensory evoked potentials (SEPs) have been studied in many disease states since they were first described by Dawson in 1947. However, there have been very few reports of SEP findings in patients with spinal cord hemisection. On the basis of clinical correlation, Giblin first postulated that the activity giving rise to the initial cortical components of the SEP travels through the dorsal column-lemniscal system. However, the pathway through which these evoked potentials are transmitted has recently been questioned. This paper examines the results of tibial nerve SEPS performed on four patients with spinal cord hemisection (Brown-Sequard syndrome). In all four cases presented, the impairment of cortical SEP components was consistently associated with stimulation of the leg ipsilateral to the side of cord injury. We conclude that the most likely mechanism of transmission is through the ipsilateral dorsal columnlemniscal system. PMID- 2930642 TI - The use of a tissue expander to enlarge a graft for surgical treatment of a pressure ulcer in a quadriplegic. Case report. AB - This case reports the use of a tissue expander to facilitate the surgical closure of a decubitus ulcer in a spinal cord injured quadriplegic. The patient is a 42 year-old man with chronic nonhealing of a right ischial pressure ulcer. It had required a flap rotation and partial ischiectomy in the remote past that had been problem-free for many years. The patient subsequently required the placement of a new flap, but insufficient tissue was available to close the wound with the hip in 90 degrees of flexion. Closing the wound with the hip in extension merely led to breakdown when the hip was put in the 90 degrees of flexion required for the sitting position. The problem was solved by using a tissue expander to increase the available soft tissue. A tissue expander was inserted and gradually expanded over a period of weeks by injecting it with fluid. It was then removed, and the expanded tissue that had grown over it allowed closure of the wound without tension on the tissues with the hip in flexion. The patient subsequently returned to the sitting position and his work as a computer programmer. Tissue expanders are commonly used in breast reconstruction, but have found many other uses in plastic surgery over the last decade. It is felt that tissue expansion techniques should not be the primary surgery treatment of decubitus ulcers, but can be used in difficult cases like this one to provide additional tissue. PMID- 2930643 TI - Increased skin temperature after vibratory stimulation. AB - The skin temperature effect of vibratory stimulation was studied in 28 healthy subjects. Vibration (50 Hz or 100 Hz) was applied to the volar surface of the left forearm for 15 min. Skin temperature of the bilateral forearms was measured before and immediately after cessation of vibration and at 5 and 10 min postvibration. Vibration at 100 Hz for 15 min on all 28 subjects was associated with a temperature increase of 4.20 +/- 0.79 degrees F that was significantly (P less than 0.01) higher than that in the controls (0.38 +/- 0.33 degrees F). Skin temperature decreased to previbration levels by 50 min of postvibration. The 11 subjects who received 50-Hz vibration for 15 min showed a skin temperature increase (0.75 +/- 0.23 degrees F) in the vibrated forearm significantly (P less than 0.01) higher than that in the control forearm (0.11 +/- 0.17 degrees F). All measurements decreased to previbration skin temperatures by 10-min postvibration. Vibration at 100 Hz also produced skin erythema in all subjects, whereas 50-Hz vibration produced no erythema. The mechanism by which 100-Hz vibration relieves pain is largely unclear, but it could be associated with increased skin temperature and erythema. PMID- 2930644 TI - Serum creatine kinase in the post-polio population. AB - Elevated creatine kinase (CK) levels may be noted in neuromuscular patients as a result of muscle damage and necrosis. We measured the serum CK levels of 62 post polio patients with chronic neurologic disease (Neuro) and 13 post-polio patients with no evidence of neurologic compromise (Control). Patient groups were comparable for age, gender and years since onset of poliomyelitis. The Neuro group had substantially increased CK levels compared with the Control group, 211 +/- 19.0 IU v 114 +/- 26.2 IU (mean +/- 1 SE; P less than 0.05). Of the Neuro group, 40% had abnormally elevated CK values, compared with 8% of the Control group. Within the Neuro group, there was a robust correlation between elevated CK values and self-reports of strenuous work and level of community ambulation (P less than 0.05). These findings support the hypothesis that chronic muscle overuse may be a contributing factor to the advanced senescence reported by post polio patients with neuromuscular compromise. PMID- 2930645 TI - Research in physical medicine and rehabilitation. II. The conceptual review of the literature or how to read more articles than you ever want to see in your entire life. AB - The purpose of the literature review is to place your research question in the context of the existing scientific literature. This article will help you to develop an overall conceptual framework to allow you to sort through the mass of published material in a focused way. The conceptual review differs from the individual article review in that it is guided by your understanding of the basic issues rather than by your knowledge of research methodology. The goal of this paper is to help you develop a conceptual framework starting from your clinical knowledge. A specific search strategy is presented to help you determine which articles are highly relevant to your topic and to locate all of these published within the past 5 years. Articles are classified into three types: those that are obviously highly relevant, other less relevant articles and articles that are potentially relevant. Guidelines are given on how to start looking, when to stop looking, how to organize the articles you find so that you can review them in a reasonable amount of time and how to read in depth the most pertinent ones you find. PMID- 2930646 TI - A test of the response deprivation hypothesis in a multiple-response context. AB - Reinforcement contingencies defined by the response deprivation hypothesis were evaluated in two multiple-response contexts. In one context a high probability response was freely available, and in the other context a low probability response was freely available. In the presence of the low probability, freely available response, a consistent reinforcement effect was evident for all 3 moderately mentally retarded participants; however, in the presence of the high probability response, the reinforcement effect was attenuated. Results were qualitatively consistent with several recent mathematical descriptions of behavior emphasizing the importance of the context in which reinforcement contingencies are introduced. PMID- 2930647 TI - Interactions, trends, and the search for order. PMID- 2930648 TI - Response deprivation: the same wine in a new bottle? PMID- 2930649 TI - Yes, context matters: behavior analysis is maturing. PMID- 2930650 TI - Toward a functional approach to learned performance. PMID- 2930651 TI - Response deprivation and the substitutability of responses. PMID- 2930652 TI - The ecology of reinforcement. PMID- 2930653 TI - Rebuilding burned bridges: analysis returns to applied behavior analysis. PMID- 2930654 TI - Effects of a freely available response on the schedule performance of mentally retarded persons. AB - The effects of a freely available response on the schedule performance of 84 mentally retarded persons were examined in a laboratory setting. Instrumental performance exceeded performance of the free response in contingent schedules; the opposite occurred in noncontingent schedules. Also, instrumental performance decreased whereas responding on the free response increased across increasing probability levels of the freely available response. We concluded that increases of instrumental performance in the response deprivation schedules employed were due to the contingency and not noncontingent deprivation and that the effectiveness of therapeutic reinforcement programs is influenced by the presence of alternative responses. PMID- 2930656 TI - Acceptability of alternative treatments for persons with mental retardation: ratings from institutional and community-based staff. AB - The acceptability of four behavior modification procedures to direct-care and supervisory staff members of community-based (Experiment 1) and institutional (Experiment 2) facilities for persons with mental retardation was evaluated. Using the Treatment Evaluation Inventory (Kazdin, 1980a), staff members rated differential reinforcement of other behavior (DRO), time-out, overcorrection, and contingent shock, each applied to a mild and a severe behavior problem. Results from both experiments showed that treatments were rated according to their restrictiveness; DRO was most acceptable, followed by time-out, overcorrection, and shock. There was also a problem by treatment interaction in each experiment. No differences were found between the ratings of direct-care and supervisory staff members in either study. Results were discussed in relation to previous treatment acceptability research. PMID- 2930655 TI - Impact of needs and resources on family plans to seek out-of-home placement. AB - The decision to maintain a severely mentally retarded child in the home or seek out-of-home placement is regarded as one aspect of family adaptation. As such, the decision is affected by numerous child-related stressors, preexistent family resources, and new sources of support. In the current study, parents with severely mentally retarded children still living at home were surveyed with regard to these variables and their plans for future child placement. Multiple regression analyses revealed that child-related stressors were negatively related to parents' plans for keeping the child at home until age 21 and positively related to plans for placing the child outside the home before age 21. Families with high levels of internal resources were more apt to report plans for keeping the child at home indefinitely. Degree of external resource use was related to plans to maintain the child at home until age 21, over-and-above both child related stressors and family resources. Specific kinds of external resources were examined and ranked ordered with regard to their usefulness to parents in maintaining their child in the home. PMID- 2930657 TI - What mentally retarded and nonretarded children expect of one another. AB - Twenty mentally retarded students and nonretarded students matched for chronological age (n = 20) or mental age (n = 16) made judgments about children described as having or not having learning problems. Results showed that students had both positive and negative stereotyped expectations about these children and that there were few differences between the expectations of retarded and nonretarded students. Students' responses to stereotype questions 11 to 18 months later revealed few changes in their stereotypes and no significant differences between stability of retarded and nonretarded students' stereotypes. Results suggest that understanding social relations between retarded and nonretarded children requires consideration of the expectations of both groups. PMID- 2930658 TI - Automatic-effortful processing and cognitive inertia in persons with mental retardation. AB - A modified Stroop Color-Word Interference Test (Stroop, 1935) was used to assess automatic-effortful processing in persons with mental retardation and college students in three experiments. In Experiment 1, retarded persons experienced greater Stroop interference than did college students. This was attributed to a failure of control (effortful) processing needed to suppress the automatic reading responses of retarded subjects. In Experiments 2 and 3, all subjects practiced the Stroop color-naming task over three or four daily sessions. Changes in Stroop interference over practice were viewed as reflecting automatization of the suppression of the reading response. Both groups automatized the suppression response at about the same rate, but the automatized responses had far greater and more durable suppression effects for retarded subjects. This persistence of automatized responses, which were no longer adaptive, was described as cognitive inertia, a phenomenon similar to cognitive rigidity as defined by Kounin (1948). PMID- 2930659 TI - Intelligence as a correlate of children's problem solving. AB - Previous work on children's problem solving was extended by directly comparing the strategies of intellectually gifted, average, and mentally retarded children on 2 two-dimensional integration problems--the balance scale and inclined plane. Comparisons of the distributions of strategies for each group showed that most gifted children integrated dimensional information by addition and many average children used lexicographic strategies. Mentally retarded children relied on a single dimension of the balance scale, but they were more likely to use lexicographic strategies for the inclined plane. Possible explanations for the large number of unclassified mentally retarded children were discussed. PMID- 2930660 TI - Risk of fractures in an intermediate care facility for persons with mental retardation. AB - The epidemiology of fractures among 553 residents of an intermediate care facility for persons with mental retardation was examined. In a 10-month period, 61 fractures occurred among 55 residents; application of fracture rates in the United States revealed an expected number of 15 fractures among the 553 residents, p less than .001. Although 52% of fractures involved small bones of the hands and feet, elderly residents were more likely to fracture major bones and to suffer their fractures from a fall than were younger residents. The relationship between potential risk factors and fracture risk were examined and implications for preventive and rehabilitative measures discussed. PMID- 2930661 TI - Exercise testing soon after myocardial infarction: its relation to course and outcome at one year in patients aged less than 55 years. AB - A consecutive series of 184 patients aged less than 55 years who had an acute myocardial infarction were enrolled in a study to examine outcome at one year. One hundred of these patients underwent a maximal exercise test six weeks after infarction to evaluate its ability to predict cardiac events. The in-hospital mortality for the series was 7.6% (14 deaths) and the one year mortality for the 170 survivors was 3.8% (seven deaths). During the exercise test 31 patients had angina and 21 had ST depression. During the one year follow up period 39 of 100 patients had angina on exertion, 15 patients underwent coronary artery surgery, three patients had a reinfarction, and one patient died. Angina during the exercise test but not ST segment depression during the exercise test predicted angina on exertion and the need for coronary artery surgery. In the year of follow up angina occurred during everyday exertion in 25 (81%) (95% confidence interval 62 to 92%) of the 31 patients who developed angina during the exercise test and in only 14 (20%) (95% confidence interval 12 to 32%) of 69 patients who did not, and coronary artery surgery was performed in 11 (35%) (95% confidence interval 19 to 54%) of the 31 patients with angina during the exercise test and only four (6%) (95% confidence interval 2 to 15%) of 69 patients without angina. The outcome after myocardial infarction in patients aged less than 55 years was good and the occurrence of angina, but not ST segment depression, during a maximal exercise test six weeks after infarction was an indication for further investigation. PMID- 2930662 TI - Cardiac and whole body [3H]noradrenaline kinetics in ischaemic heart disease: contrast between unstable anginal syndromes and pacing induced ischaemia. AB - Radiotracer kinetics were used to evaluate the activity of the sympathetic nervous system in 10 patients who had had unstable ischaemic symptoms within the previous 12 weeks and 10 with stable angina. Patients with recent unstable angina or angina after recent acute myocardial infarction had higher basal cardiac noradrenaline spillover than patients with stable angina. This represents a selective increase in cardiac sympathetic tone because whole body noradrenaline spillover was not significantly increased in the patients with recent unstable angina. Atrial pacing in 15 patients caused angina in 13 but did not significantly alter cardiac noradrenaline spillover in either patients with stable or unstable angina. The flow of plasma in the coronary sinus increased during pacing but because cardiac noradrenaline extraction decreased cardiac noradrenaline clearance was not significantly altered. Both whole body noradrenaline spillover and clearance were modestly increased by pacing, and arterial noradrenaline concentration was unchanged. Patients with recent symptoms of unstable ischaemia had a sustained and selective increase in cardiac efferent sympathetic tone compared with patients with stable angina, and angina induced by atrial pacing did not cause important cardiac sympathetic activation. PMID- 2930663 TI - Left ventricular filling and early diastolic function at rest and during angina in patients with coronary artery disease. AB - Left ventricular diastolic function was studied in 11 patients with coronary artery disease. Single plane ventriculography (30 degrees right anterior oblique projection) was performed at rest and during an episode of angina immediately after a period of rapid atrial pacing. Left ventricular pressure was recorded simultaneously by a micromanometer tipped catheter. The ventriculograms were digitised frame by frame to derive continuous plots of left ventricular shape, volume, and rate of change of volume. The time constant (tau) of the fall in left ventricular pressure was determined from the exponential portion of pressure decay during isovolumic relaxation. Ventricular pressure-volume loops were constructed to study the left ventricular diastolic pressure-volume relation. The time of minimum left ventricular pressure was used to divide diastole into an early phase and a late phase. Angina was associated with an increase in end systolic volume and a fall in ejection fraction with no significant change in end diastolic volume. Peak left ventricular pressure was unchanged but left ventricular minimum and end diastolic pressures were both increased and the diastolic pressure-volume relation was moved upwards. The time constant of left ventricular pressure fall was prolonged. At rest more than 50% of the stroke volume entered the left ventricle during the period of early diastole. This proportion was significantly reduced during angina and as a consequence a significantly greater proportion of the stroke volume entered the ventricle during late diastole. Despite this, and although the left ventricular diastolic pressure-volume relation was moved upwards with angina, the mean slope of the relation during late diastole--that is, chamber stiffness--was not significantly altered. The upward shift of the left ventricular diastolic pressure-volume relation seen during angina is thus already apparent in early diastole, and its extent does not change during the later phase of diastole, which alone shows the property of passive stiffness. A primary increase in the passive stiffness of the ventricle cannot therefore be the cause of the upward shift of the diastolic pressure-volume relation, and events occurring in early diastole have to be looked to for an explanation. The study findings show that left ventricular function in early diastole is profoundly disturbed during angina pectoris and it is suggested that loss of elastic recoil and dissipation of this restoring force by asynchronous onset of relaxation and abnormal changes in shape are important factors contributing to this disturbance of function. PMID- 2930664 TI - Electrophysiological study of young patients with exercise related paroxysms of palpitation: role of atropine and isoprenaline for initiation of supraventricular tachycardia. AB - Electrophysiological studies were performed in eight patients (four men and four women, mean (SD) age 24 (5) years with paroxysmal attacks of palpitation during or immediately after exercise. Five patients were competitive athletes at college. In two patients spontaneous supraventricular tachycardia during exercise was recorded by ambulatory electrocardiographic monitoring and in another it was induced by treadmill exercise testing. Two had dual atrioventricular nodal pathways, three had manifest atrioventricular accessory pathways, and three had concealed atrioventricular pathways. Programmed stimulation induced sustained supraventricular tachycardia in six patients--in two after intravenous injection of atropine sulphate (1 mg) and in four during infusion of isoprenaline (0.01 microgram/kg/min). In one patient, non-sustained atrioventricular nodal reentrant tachycardia was induced during isoprenaline infusion. In the remaining patient, who had dual atrioventricular nodal pathways, tachycardia was not inducible. AH block prevented maintenance of reentry in five patients. In five patients shortening of the effective refractory period of the atrioventricular node with atropine (one patient) and isoprenaline (four patients) caused sustained supraventricular tachycardia. The present study indicates that treatment with atropine and isoprenaline may be an important factor in the initiation of supraventricular tachycardia in patients with exercise related paroxysms of palpitation. PMID- 2930665 TI - Sinus arrhythmia in children with atrial septal defect: an analysis of heart rate variability before and after surgical repair. AB - The expression of sinus arrhythmia depends on separation of the systemic and pulmonary venous return to the heart as well as on normal autonomic control mechanisms. Patients with atrial septal defect provide a naturally occurring experiment of communication between the two venous systems. In adults with atrial septal defect sinus arrhythmia is minimal or absent. But children with atrial septal defect retain appreciable sinus arrhythmia, although this is not recognised in published reports. To understand why this is so, continuous electrocardiograms were recorded before and after operation in 10 children (aged 4-16 years, mean 6.3) with atrial septal defects and in 10 normal children (aged 5-7 years, mean 6.1). Mean RR intervals were calculated for periods of one minute, and the standard deviation was used as an index of heart rate variability (that is sinus arrhythmia). Frequency analysis (spectral analysis) was also performed on a continuous beat to beat record of heart rate to describe the frequency components that may reflect autonomic activity. The results confirmed the presence of considerable sinus arrhythmia in children with unoperated atrial septal defect. None the less, the standard deviation of RR intervals in the children with unoperated atrial septal defect was significantly less than that for the normal children, and variation increased after closure of the defect. Power spectral analysis of instantaneous heart rate indicated that the high frequency (0.15-0.45 Hz) vagally mediated component of variability was lower for patients than for controls which may indicate abnormalities of autonomic control of heart rate in these children. The comparative retention of sinus arrhythmia in children with atrial septal defect may relate to the small size of the right atrium or differences in myocardial compliance compared with adults. PMID- 2930666 TI - Cross sectional echocardiography for recognition of ventricular topology in atrioventricular septal defect. AB - The cross sectional echocardiograms of 150 children with atrioventricular septal defects were reviewed to determine the spatial orientation of the ventricles. In 125 cases with usual atrial arrangement (situs solitus), ventricular topology showed the right hand pattern. Of the 25 patients with atrial isomerism, 13 had similar right hand topology but 12 (48%) had the left hand pattern. This finding was more common in hearts in the right side of the chest (dextrocardia), but there was no significant correlation between ventricular topology and number of atrioventricular valves or the ventriculoarterial connection. In part because of inferences for disposition of the conducting tissue, knowledge of ventricular topology is important when operation for atrioventricular septal defects is considered. Ventricular topology can be promptly recognised by cross sectional echocardiography. PMID- 2930667 TI - Cardiac abnormalities in the fragile X syndrome. AB - Twenty three patients with fragile X syndrome underwent cardiovascular assessment. Echocardiography showed dilatation of the aortic root in 12 (52%) and mitral valve prolapse in five (22%), four of whom had an apical mid-systolic click on auscultation. Patients with fragile X syndrome have cardiac defects similar to those seen in other disorders of connective tissue such as Marfan's syndrome and Ehlers-Danlos syndrome. These, and other somatic features, suggest an underlying connective tissue dysplasia. PMID- 2930668 TI - Genetic evidence that mutations in the COL1A1, COL1A2, COL3A1, or COL5A2 collagen genes are not responsible for mitral valve prolapse. AB - DNA markers were used to assess the segregation of genes encoding the collagen types that predominate in the mitral valve (types I, III, and V) in two family pedigrees that are phenotypically different but showed dominantly inherited mitral valve prolapse. The inheritance of these markers was compared with the segregation of the phenotype for mitral valve prolapse in both families. In one family it was shown that the COL1A1, COL1A2, COL3A1, and COL5A2 genes segregated independently of the phenotype; in the other family the results for COL1A1, COL1A2, and COL5A2 were similar but analysis at the COL3A1 locus was not possible. These data indicate that in these families mitral valve prolapse does not arise from a defect in one of these collagen genes. PMID- 2930669 TI - Genetic segregation analysis of familial mitral valve prolapse shows no linkage to fibrillar collagen genes. AB - Three pedigrees were identified in which mitral valve prolapse seemed to be inherited as a mendelian autosomal dominant trait. The segregation of the genes encoding the major fibrillar collagens present in valve tissue, collagens I and III, was analysed by use of restriction enzyme site variants as genetic markers. In one pedigree there was discordance between the segregation of the disease and markers for all three collagen genes. In another, there was discordance between the disease and markers for both collagen I loci. This is evidence against the disease being generally the result of mutations of the genes encoding the major fibrillar collagens. PMID- 2930671 TI - Preoxygenation. PMID- 2930670 TI - Acute myocardial infarction in infancy: unmasking of anomalous origin of the left coronary artery from the pulmonary artery by ligation of an arterial duct. AB - Myocardial infarction and left ventricular failure developed within hours of ligation of a large arterial duct in a four week old infant. Anomalous origin of the left coronary artery from the pulmonary artery was confirmed by echocardiography. Despite emergency translocation of the anomalous coronary artery the patient died. PMID- 2930672 TI - Effects of halothane on somatosensory evoked potentials recorded in the extradural space. AB - We studied the effects of supplementing anaesthesia with halothane (up to 1.5%, inspired) on the somatosensory evoked potential recorded in the extradural space of six patients before corrective surgery for idiopathic adolescent scoliosis. A further six patients in whom anaesthesia was supplemented with thiopentone acted as a control group. Halothane 1.5% resulted in a significant decrease in overall amplitude (P less than 0.05) from the left leg only. Halothane had no significant effect on overall amplitude, first peak amplitude, second peak amplitude and first peak latency. We conclude that halothane is unlikely to alter the interpretation of somatosensory evoked potentials recorded extradurally during scoliosis surgery. A possible unilateral effect of halothane on the concave side in idiopathic adolescent scoliosis needs further investigation. PMID- 2930673 TI - Maternal oxygenation during normal labour. AB - Arterial oxyhaemoglobin saturation (SaO2) was monitored continuously during normal labour in 33 healthy parturients receiving pethidine and nitrous oxide for analgesia. Sixteen (49%) had episodes exceeding 10 s duration when SaO2 was less than 90% (mean 83.7%, range 89-60%). Two women had multiple episodes of profound hypoxia with SaO2 less than 70%. PMID- 2930674 TI - Interaction of ketamine with atracurium. AB - The effect of ketamine on the duration of atracurium-induced neuromuscular blockade was studied in 40 healthy patients anaesthetized with midazolam, fentanyl and nitrous oxide. Twenty received, in addition, i.v. ketamine 2 mg kg-1 followed by an infusion of 2 mg kg-1 h-1. Atracurium 0.5 mg kg-1 was injected i.v. and the time to 25% recovery of the twitch height was measured. It was 8.0 min longer in the ketamine group (P less than 0.005), with a 95% confidence interval of from 2.3 to 11.8 min. PMID- 2930675 TI - Natural killer cell activity in a patient undergoing resection of phaeochromocytoma. AB - This report describes the relationship between plasma catecholamine concentrations and natural killer (NK) cell activity in a patient undergoing surgical removal of a phaeochromocytoma. The findings confirm the role of adrenaline as a potent stimulator/inducer of NK cell cytotoxicity in vivo. PMID- 2930676 TI - Anaesthetic management of a patient with facioscapulohumeral muscular dystrophy. AB - We describe the anaesthetic management of a patient with a rare form of muscular dystrophy (Facioscapulohumeral or Landouzy-Dejerine type). Anaesthesia and controlled ventilation using alfentanil-nitrous oxide and atracurium was satisfactory. In this patient, sensitivity to atracurium was found to be similar to that of the normal population, but more rapid recovery was observed. PMID- 2930678 TI - Bilateral pneumothorax following tracheal intubation. AB - An elderly patient undergoing elective cholecystectomy, developed bilateral pneumothorax following intubation of the trachea and manual ventilation of the lungs. Diagnosis was confirmed by chest x-ray and drainage with wide bore cannulae. Drainage of the chest was necessary. PMID- 2930677 TI - Complications of spinal anaesthesia following extradural block for caesarean section. AB - After extradural blockade failed to extend sufficiently for elective Caesarean section, spinal anaesthesia was performed using 1.6 ml of hyperbaric 0.5% bupivacaine solution in 8% glucose (Marcain Heavy). The patient rapidly developed sensory blockade to the level of T2, and became distressed and dyspnoeic. General anaesthesia was induced. Despite i.v. ephedrine and fluid loading, severe hypotension occurred, which responded subsequently to further doses of ephedrine and infusion of colloid. A healthy infant was delivered by Caesarean section. PMID- 2930679 TI - The blood lancet in regional anaesthesia. PMID- 2930680 TI - Effect of suxamethonium given during recovery from atracurium. PMID- 2930681 TI - High intrinsic radiosensitivity of a newly established and characterised human embryonal rhabdomyosarcoma cell line. AB - A new human rhabdomyosarcoma cell line (HX170c) has been established from a paratesticular embryonal tumour in a 5-year-old male. The cells grew as an adherent monolayer with a doubling time of 32 h and showed pleomorphic features. Intermediate filament analysis revealed the line to be mesenchymal in origin (reactivity to vimentin and desmin antibodies). The line was tumorigenic in nude mice, possessed elevated levels of creatine phosphokinase (mainly of the MM isoenzyme form) and had a near diploid mean chromosome number of 50. In vitro cell cloning determinations gave colony forming efficiencies of 0.01% in soft agar and 24% in a monolayer anchorage-dependent assay. Radiosensitivity determinations using a monolayer clonogenic assay with feeder layer support showed the cells to be among the more radiosensitive human tumour cell types (surviving fraction at 2 Gy of 0.26) that have been investigated. Furthermore, experiments utilising continuous low dose rate radiation at 3.2 cGy min-1, showed that, under these experimental conditions, the cells possessed only a very low capacity to recover from radiation-induced damage (dose reduction factor at 1% cell survival of 1.07 for 150 versus 3.2 cGy min-1). As other human tumour cells of an embryonal cell origin (e.g. neuroblastoma and germ cell tumours of the testis) have also been shown to be radiosensitive it appears that sensitivity to radiation may be a common property of this group of tumours. PMID- 2930682 TI - Warfarin inhibits metastasis of Mtln3 rat mammary carcinoma without affecting primary tumour growth. AB - Coumarin anticoagulants inhibit metastasis in several animal models, but the mechanism of this effect is uncertain. In order to determine the role of cytotoxic and/or cytostatic actions of coumarins on the tumour cells, we have studied the effects of warfarin on tumour cell growth in a model in which tumour metastasis is inhibited by this drug. Clonogenic assay, growth curve analysis and thymidine labelling index revealed that warfarin had no effects on Mtln3 mammary carcinoma cell growth in vitro at concentrations below 1 mM. The growth rate of subcutaneously implanted Mtln3 tumour deposits in female F344 rats, assessed by weight and by stathmokinetic analysis of the tumour tissue, was identical in warfarin-treated and control animals. Spontaneous metastasis from such tumours to the lungs was, however, significantly reduced in warfarin-treated animals (median 0 pulmonary tumours per animal in warfarin treated, eight tumours per animal in control animals; P less than 0.05, Mann-Whitney). The mean plasma warfarin concentration in warfarin treated rats was 1.63 microM. These results suggest that warfarin treatment of the host animal can inhibit tumour metastasis without having any direct or indirect effect on the growth rate of the tumour cells. PMID- 2930683 TI - The distribution of porphyrins with different tumour localising ability among human plasma proteins. AB - The distribution among the main fractions of human plasma lipoproteins of a number of porphyrins with different tumour localising ability has been determined by means of ultracentrifugation. A main trend is that the fraction of the dyes that are bound to low density lipoprotein (LDL) increases, and the fraction bound to HSA decreases with decreasing polarity of the dyes. An asymmetric charge distribution, such as in TPPS2a, favours LDL-binding more than expected on the basis of lipophilicity. No correlation between the known tumour localising ability of the drugs tested in the present work and their relative affinity for LDL was found. One of the best tumour localisers reported in the literature, TPPS4, hardly binds to LDL, while Hp and Pp, which are commonly considered inefficient tumour localisers, do have a significant affinity for LDL. On the other hand, the LDL binding capacity for a drug is suggested to be a good index for cellular uptake. Such an index does not necessarily imply that the actual uptake occurs by the LDL pathway. PMID- 2930684 TI - Relationship between tumour cell morphology, gap junctions and susceptibility to cytolysis by tumour necrosis factor. AB - Tumour necrosis factor (TNF) is directly cytolytic to certain tumour cell lines in vitro, although TNF-resistant variants can be selected from these susceptible lines by exposure to TNF. While studying TNF-susceptible L929 cells and their resistant variant, L929/R, we noted that within L929 colonies the cells were widely spaced whereas they were closely packed in L929/R colonies. L929/R cells also adhered more strongly to plastic and differed from L929 in cell shape. Similar observations were made with TNF susceptible and resistant variants of two other cell lines (RK13 and a plastic adherent U937 subline). The tendency of resistant cells to grow closely together suggests the possibility of inter-cell communication for the TNF resistant state. However, like L929 and U937, L929/R and U937/R did not communicate by gap junctions and we could find no evidence of extracellular mediators of TNF resistance. Rather the differences in colonial morphology, cell shape and plastic adherence may be secondary to an underlying mechanism which defines TNF susceptibility/resistance. PMID- 2930685 TI - The inhibition of murine lung metastasis by synthetic polypeptides [poly(arg-gly asp) and poly(tyr-ile-gly-ser-arg)] with a core sequence of cell adhesion molecules. PMID- 2930686 TI - Diploid nature of hepatocellular tumours developing from transplanted preneoplastic liver cells. AB - Hepatocyte suspensions were transplanted to the livers of syngeneic Wistar Kyoto rats by means of intraportal injection. Labelling of the donor cells with 51Cr or tritiated thymidine showed that 20% of the cells survived the transplantation procedure and were permanently retained by the recipient liver. Hepatocytes transplanted from normal livers produced no tumours, whereas donor cells from preneoplastic livers of rats treated with the carcinogens diethylnitrosamine and 2-acetylaminofluorene produced neoplastic nodules and hepatocellular carcinomas in the recipients. The number of tumours per host liver was proportional to the number of hepatocytes transplanted. Treatment of the host rats with phenobarbitone accelerated tumour development, causing liver cancer in the majority of the animals within three months. As opposed to the polyploid surrounding liver, both phenobarbitone-promoted and unpromoted host tumours contained predominantly (70-90%) diploid cells, regardless of the wide range of transplant ploidies (10-80% diploid cells) achieved by means of centrifugal elutriation. The results indicate that all host tumours arise from diploid donor hepatocytes and that the acquisition of a constitutive, predominantly non polyploidising growth pattern may be a characteristic property of hepatocellular tumours. PMID- 2930687 TI - Comparison of the rapid automated MTT-assay with a dye exclusion assay for chemosensitivity testing in childhood leukaemia. PMID- 2930688 TI - Survival and prognostic factors in differentiated thyroid cancer--a multivariate analysis of 1,055 cases. AB - Survival (5- and 10-year) and prognostic factors of all differentiated thyroid cancer patients (n = 1,055) occurring in Norway in 1970-79 are presented. The multivariate analysis (GLIM) revealed that stage and age were the only significant prognostic factors. Sex and histological type could not be proved to be of major prognostic value. The decline in relative survival with age was different in the three stages, appearing as a continuous decrease in stage 3, while in stage 1 the decrease was present only in patients older than 75 years. PMID- 2930689 TI - Metoclopramide enhances the effect of cisplatin on xenografted squamous cell carcinoma of the head and neck. AB - The chromatin-bound enzyme adenosine diphosphate ribosyl transferase is activated by DNA-damaging agents. Substances that inhibit the enzyme, such as benzamide analogues, are known to increase the cytotoxicity of ionising radiation and cytotoxic drugs. The purpose of the present study was to investigate whether the anti-emetic drug metoclopramide, a benzamide derivative (4-amino-N-2 (diethylaminoethyl)-5-chloro-2-methoxybenzamide; MCA), potentiates the effect of cisplatin (cis-diammine-dichloroplatinum; CDDP) on squamous cell carcinoma (SCC). For that purpose human SCC of the head and neck (i.e. tumour line AB and EH) xenografted to nude mice were used. Two administration schedules were tested: (a) MCA (2.0 mg kg-1 i.p.) one hour before CDDP (7.5 mg kg-1 i.p.); and (b) MCA (3 x 2.0 mg kg-1) given concomitant to, 24 and 48 hours after CDDP (7.5 mg kg-1) administration. Treatment efficacies were compared using the area under the growth curves (AUC), tumour volumes and specific growth delay (SGD). There was no mortality and no weight loss of significance in any treatment group. MCA alone did not induce any significant reduction in AUC, tumour volume or SGD with either treatment schedule. CDDP alone gave a significant reduction of tumour growth in tumour line AB but not in tumour line EH. In schedule (a) the addition of MCA did not give any additive effect. However, in schedule (b), for both tumour lines, MCA enhanced the effect of CDDP by significantly reducing the AUC (AB: P less than 0.0001; EH: P less than 0.001) and increasing SGD (AB: P less than 0.012; EH: P less than 0.001) when compared to the tumours given CDDP alone. These effects were observed at a MCA dose currently being administered to humans. PMID- 2930690 TI - Phase II study of lonidamine in metastatic breast cancer. AB - Thirty patients with previously treated metastatic breast cancer were entered in a phase II study with oral lonidamine. Twenty-eight patients are evaluable for toxicity and 25 for response. A partial remission was obtained in four patients (16%) and disease stability in 11 (44%): 10 patients progressed (40%). Toxicity was acceptable, consisting mainly of myalgias (39% of patients) and asthenia (21.4%). No myelotoxicity was observed. The drug is active in previously treated metastatic breast cancer and, because of its peculiar pattern of action and toxicity, deserves to be evaluated in combination with cytotoxic chemotherapy. PMID- 2930691 TI - Breast cancer, prostaglandins and patient survival. AB - Prostaglandins may have both undesirable and desirable effects in malignant disease. Their possible roles in breast cancer were studied by examining the relationships between different variables and the amounts of prostaglandin-like material (PG-LM) extracted from 141 breast carcinomas. Univariate analysis indicates a direct correlation with patient age and menopausal status, with a greater yield from cancers of post- compared with pre-menopausal women. Tumours up to 2 cm diameter yielded more PG-LM than those measuring greater than 2-5 cm. Although there was also a direct correlation with bone metastasis near to the time of surgery, this was because no positive bone scans occurred in patients whose tumours yielded little total PG-LM (less than 16 ng PGE2 equivalents per g tissue). Since tumour PG-LM did not predict later spread to bone, and yields of greater than 16 ng g-1 were similar in the positive and negative bone scan groups, tumour PG-LM appears to be unimportant for skeletal metastasis. There was no obvious relationship of tumour PG-LM to the grade of malignancy, tumour type, amounts of fibrous tissue (and therefore malignant cells), invasion of blood vessels and lymphatics or presence of plasma cells. Multivariate analysis indicates that disease-free survival is longest with an intermediate production of tumour total PG-LM. Of the 82 patients now dead, the cause was attributed to metastatic disease in 69 cases. No relationship of PG-LM to the length of survival was seen with univariate or multivariate analysis. However, when just the post-menopausal patients who died within the first 3 postoperative years were analysed, there was a highly significant inverse correlation between the tumour total PG-LM and the time to death. The reason(s) for these different findings on overall survival compared with just the patients who died are not understood, but the results may indicate that one or more other variables must co-exist with a high tumour PG-LM to hasten death. PMID- 2930692 TI - Prognostic factors in high and intermediate grade non-Hodgkin's lymphoma. AB - An analysis of prognostic factors has been performed on 260 patients with high and intermediate grade non-Hodgkin's lymphoma (NHL) treated over an 11-year period between 1975 and 1986. The overall 5-year survival rate was 50% with a median follow-up of 72 months. Over 20 clinical, radiological and laboratory parameters have been studied, including variables reported to be important indicators of prognosis in previous series, and these variables have been subjected to univariate and multivariate analysis. Attainment of complete remission (CR) was the most important predictor of overall survival, low serum lactate dehydrogenase (LDH), limited stage disease and a high serum albumin were also independently associated with prolonged survival in multivariate analysis. After removing remission status from the model, Ann Arbor clinical stage became the most significant pre-treatment prognostic indicator. Sixty-five per cent of patients achieved CR, and a discriminant analysis showed that failure to attain CR was associated with advanced stage disease, constitutional symptoms, increasing patient age, a low serum albumin and the presence of bulk disease. Advanced clinical stage and an elevated serum LDH predicted independently for a poor relapse-free survival, and reduced overall survival following CR. There was no significant correlation between histological subtype in the Kiel classification and prognosis. This study confirms the prognostic significance of remission status and Ann Arbor clinical stage, and illustrates additional factors including serum levels of albumin and LDH, which serve to enhance the pre treatment prognostic evaluation of patients with unfavourable histology NHL. PMID- 2930693 TI - Circulating CA 15-3 antigen levels in non-mammary malignancies. AB - Abnormal CA 15-3 antigen levels are found in the serum of most patients with advanced breast carcinoma. Elevations of this marker are less frequently seen in other malignancies. Circulating CA 15-3 levels might be useful in the differential diagnosis of the primary site of cancer. We studied the levels of CA 15-3 in 500 patients with different non-mammary cancers. Elevations of CA 15-3 (greater than 40 U ml-1) were observed in all types of epithelial malignancies, especially in ovarian (46%), respiratory (26%) and liver (30%) carcinomas. Abnormal values were observed in some patients with haematological malignancies and sarcomas, but not in melanoma or neurological tumours. CA 15-3 antigen levels correlated with the extent of non-mammary malignant tumours. Patients with locoregional cancer had a significantly smaller proportion of elevations of the antigen than those with distant metastases (12% versus 35%, P less than 0.001). In particular, elevated CA 15-3 levels were observed in 70% of patients with metastatic ovarian cancer. Liver involvement by cancer did not produce more elevations of CA 15-3 than metastases to other organs (32% versus 39%). Simultaneous determination of circulating CA 15-3 and CA 125 antigens in 58 patients with cancer of the ovary showed that CA 15-3 is elevated in some cases of ovarian carcinoma with non-elevated CA 125, and that CA 15-3 and CA 125 are distinct antigens. We conclude that circulating CA 15-3 antigen levels can be found elevated in virtually all types of cancer, particularly when distant metastases are present. Therefore, CA 15-3 levels should not be used in the differential diagnosis of the primary site in patients with metastatic malignancies of unknown origin. Evaluation of CA 15-3 levels may enhance the sensitivity of CA 125 in monitoring the course of ovarian carcinoma. PMID- 2930694 TI - 5-FU therapeutic monitoring with dose adjustment leads to an improved therapeutic index in head and neck cancer. AB - This 4 year study reports on a pharmacokinetic study for the widely used regimen of cis-platin plus continuous 5-day 5-FU as first-line chemotherapy of head and neck cancer, and the benefit of such data for real-time therapy management. Pharmacokinetic analysis of 177 cycles for 77 patients from a group of 89 patients (group 1; 228 cycles) revealed that both the time-concentration product (AUC) for the entire cycle and the half-cycle AUC (AUC0-3 days) were predictive of cycle toxicity. Real-time analysis of individual AUC0-3 days was used to decide whether to reduce the dose during the second half of the cycle for a total of 249 cycles (81 patients; group 2). The dose in the second half of the course was reduced in 40% of the group 2 courses. There was a statistical difference in complete response rates between group 1 (31%) and group 2 (47%), (0.02 less than P less than 0.05) and a statistically significant reduction was observed in the incidence of toxic cycles (greater than grade 2, group 1 = 20% versus group 2 = 12.4%; 0.02 less than P less than 0.05). Pharmacokinetic follow-up of these patients has proved to be an objective means to improve therapeutic index significantly. PMID- 2930695 TI - The detection of axillary lymph node metastases from breast cancer by radiolabelled monoclonal antibodies: a prospective study. AB - In a prospective study to assess the accuracy of monoclonal immunoscintigraphy for the detection of axillary lymph node metastases in breast cancer, two murine monoclonal antibodies that react with human breast cancer (3E1.2 and RCC-1) were labelled with 131iodine, and the radiolabelled antibody was injected subcutaneously into the interdigital spaces of both hands of 40 patients, 36 of whom had breast cancer and the remaining four of whom had fibroadenoma (the normal, contralateral axilla was used as a control). Of the patients with breast cancer, the findings from the scintigraphy images were correlated with histopathology or cytology of the axillary lymph nodes; images were regarded as positive and hence indicative of lymph node metastases if the amount of background-subtracted radioactive count in axilla on the side of breast cancer exceeded the contralateral normal side by a ratio greater than or equal to 1.5:1.0 as assessed by computer analysis. Using this method, immunoscintigraphy had an overall sensitivity of 33% (23% with 131I-3E1.2 and 50% with 131I-RCC-1) for the detection of lymph node metastases and a specificity of 63% (67% with 131I-3E1.2 and 60% with 131I-RCC-1) with problems of non-specific uptake by presumably normal lymph nodes. The results of immunoscintigraphy obtained with 131I-RCC-1 (IgG) were superior to 131I-3E1.2 (IgM) although the accuracy of immunoscintigraphy using 131I-RCC-1 (56%) was not much better than preoperative clinical assessment (50%). However, there were cases when immunoscintigraphy using radiolabelled antibody (IgM or IgG) detected axillary lymph node metastases not suspected by clinical examination. Thus it appears that while immunoscintigraphy may be a useful adjunct to preoperative clinical assessment and is simple and safe, a major improvement in its accuracy is needed before it can replace axillary dissection and histological examination in the accurate staging of axilla in breast cancer. PMID- 2930696 TI - Anticancer efficacy of 2-chloroethylnitrosocarbamoyl derivatives of L-alanine, glycine, their di- and tripeptide homologues and the respective amides in methylnitrosourea-induced rat mammary carcinoma. PMID- 2930697 TI - Enhanced anti-proliferative action of busulphan by quercetin on the human leukaemia cell line K562. PMID- 2930698 TI - The effect of hypobaric hypoxia on misonidazole binding in normal and tumour bearing mice. AB - The effect of hypobaric hypoxia on the in vivo binding of misonidazole was investigated in normal mice and mice bearing T50/80 or CA NT mammary carcinomas. After the intraperitoneal injection of radiolabelled misonidazole, mice were randomised to breathe either room air or air at 0.5 atmospheres. The distribution of misonidazole in liver, kidney, heart, spleen and tumour tissue, 24 h later, was studied by scintillation counting and by autoradiography. Significantly higher misonidazole binding occurred in the livers (x2.5), kidneys (x2.4), spleens (x2.9) and hearts (x1.8) of hypoxic mice compared to controls. Hypobaric hypoxia was associated with a greater than four-fold increase in misonidazole binding within T50/80 tumours. However, significantly higher binding was not demonstrated within CA NT tumours after exposure of tumour-bearing animals to hypoxic conditions. In autoradiographs of hypoxic liver, labelling was intense in regions near to hepatic veins but sparse in areas surrounding portal tracts. This pattern was striking and consistent. In hypoxic kidney, labelling was most intense over tubular cells, less intense over glomeruli and sparse in the renal medulla. It is likely that the hepatic and renal cortical distributions of misonidazole binding reflect local oxygen gradients. PMID- 2930699 TI - Cytotoxin from polymorphonuclear leukocytes and inflammatory ascitic fluids. PMID- 2930700 TI - Specific targeting and toxicity of sulphonated aluminium phthalocyanine photosensitised liposomes directed to cells by monoclonal antibody in vitro. AB - A partially purified fraction of the water soluble photosensitive dye sulphonated aluminium phthalocyanine (AlSPc) was encapsulated in liposomes which were then linked to a targeting monoclonal antibody 791T/36 using a heterobifunctional linking agent. The photocytotoxic effects of the liposomes were determined on two cell lines bearing an antigen with which the targeting antibody binds: 791T, an osteosarcoma and C170, a colorectal carcinoma; and a control cell line not bearing the antigen; DW-BCL, an Epstein-Barr virus immortalised B-cell line. Antibody dependent cytotoxicity was observed in 791T and C170 cells and was proportional to the number of antigens on the cells, the AlSPc concentration and the time of exposure to activating red light. No significant toxicity was seen using untargeted liposomes, control cells or free AlSPc fraction under similar conditions. Targeted cells and controls kept in the dark also showed no significant toxicity. A possible mechanism of action is postulated and simple adaptations which demonstrate the versatility of the model are discussed. Some suggestions as to the clinical situations to which this system might be applied in the form of photodynamic therapy (PDT) are made. PMID- 2930701 TI - Reducing the hypoxic fraction of a tumour model by growth in low glucose. AB - The question of whether growth under low glucose conditions leads to a reduced amount of cell hypoxia was investigated using an in vitro tumour analogue, the sandwich system. In this multicellular system, the interplay between diffusion and consumption of oxygen and nutrients results in spatial gradients of these environmental factors. Gradients in the environment lead to biological heterogeneity within the cell population. A necrotic centre, surrounded by a viable cell border, subsequently develops. Cells adjacent to the necrotic centre in sandwiches are hypoxic and are in an environment somewhat analogous to that of cells adjacent to necrotic regions in solid tumours. Using sandwiches of the 9L and V79 cell lines, the effects of growth under low glucose conditions on the degree of hypoxia in regions adjacent to the necrotic centre were investigated. Per-cell binding of 3H-misonidazole, assessed by autoradiography, was used as an indicator of oxygen deprivation. It was found that the extent of the hypoxic region and the severity of hypoxia were considerably reduced by growing sandwiches in a glucose concentration of 0.6 mM rather than 6.5 mM. This reduction was found in conjunction with a smaller viable border; it occurred despite the fact that the average per-cell oxygen consumption is higher in the low glucose sandwiches. The data are qualitatively consistent with a joint oxygen glucose deprivation model for cell necrosis. PMID- 2930702 TI - Potentiation of methotrexate lymphocytotoxicity in vitro by inhibitors of nucleoside transport. AB - Modulation of nucleic acid antimetabolite cytotoxicity by preformed purines and pyrimidines may not only complicate the interpretation of drug sensitivity tests and other in vitro studies but also adversely affect treatment in vivo. Previously we reported that in a lymphocyte clonal assay, thymidine and hypoxanthine released from dead or damaged cells reduced methotrexate cytotoxicity. We now report that the nucleoside transport inhibitor dipyridamole (DP), at 1.0 microM, abolished 3H-thymidine uptake into PHA stimulated lymphocytes, potentiated methotrexate cytotoxicity and reversed modulation of methotrexate cytotoxicity by exogenous thymidine and hypoxanthine. Normal growth of lymphocytes at high density was unaffected by 1.0-5.0 microM dipyridamole, while growth at low densities was only slightly reduced. Hydroxy nitrobenzylthioguanosine (555) was a less potent inhibitor of 3H-thymidine uptake and was toxic to normal lymphocytes at concentrations inhibiting 3H-thymidine uptake. Nucleoside transport inhibitors isolate the cellular effects of nucleic acid antimetabolites, and provide a tool to study mechanisms of antifolate cytotoxicity. PMID- 2930703 TI - The clonal origin of experimental large bowel tumours. PMID- 2930704 TI - Clinical trials in cancer: the role of surrogate patients in defining what constitutes an ethically acceptable clinical experiment. AB - Doctors who treat lung cancer in Ontario were previously asked how they would wish to be managed if they developed non-small cell lung cancer and whether they would consent to participate in six clinical trials for which they might be eligible. The proportion of these expert surrogate patients who would consent to each clinical trial ranged from 11 to 64%. The results of this study were transmitted to the same group of doctors who were asked to comment on the ethical acceptability of each trial in the light of this information. The majority of physicians said that those trials to which less than 50% of expert surrogates consented should not have been opened to patients. Sixty-nine per cent of doctors thought that new trials should be evaluated in this way. We also present the results of a survey of 400 lay people in Ontario who were asked to imagine that they had lung cancer and whether they would consent to participate in two of these same clinical trials. Fifty per cent of lay people consented to a randomised trial of lobectomy versus segmentectomy in early, operable disease (LCSC-821) compared to 64% of expert surrogates, and 48% of lay people consented to a randomised trial of five different forms of chemotherapy in metastatic disease (SWOG-8241) compared to 19% of doctors. It was concluded that the lay people were unable to discern differences in the acceptability of clinical trials which were clear to experts in the field. Subsequently, respondents were told about the decisions which doctors would make in the same circumstances and asked if this information would modify their previous decisions. There is no net change in the proportion of patients consenting to the surgery trial but the proportion of people consenting to the chemotherapy trial decreased by 40%. The majority of lay people said that they would wish to have access to this type of information before consenting to participate in a clinical trial. PMID- 2930705 TI - The size of clinical trials in cancer research--what are the current needs? Medical Research Council Cancer Therapy Committee. AB - Most randomised clinical trials of cancer treatment include a few hundred patients or less. Recent statistical papers advocate that sometimes thousands of patients should be entered. In this paper I show that for certain types of cancer trials the 'thousands policy' is not required while for others it is desirable but not feasible. In the latter case other strategies should be considered, such as two-stage phase III studies or parallel studies leading to overviews. There is, however, an important subset of trials for which application of the thousands policy is both necessary and feasible. The key to progress lies partly in the achievement of greater recruitment rates in trails of common cancers and partly in greater inter-group collaboration. PMID- 2930706 TI - Cell kinetics in acute lymphoblastic leukaemia: comparative analysis between adults and children. AB - Cell kinetics were studied in 124 patients with acute lymphoblastic leukaemia (ALL) by flow cytometry, comparing cell cycle characteristics between adults (57 cases) and children (67 cases). S, G2 + M and the low protein content fraction of G1 (LPC fraction) were determined and studied in relation to other clinical and biological features. No difference was found between adults and children in the distribution of these variables. The proliferative rates according to organomegaly, leukocytosis, the FAB cytological groups and the immunological groups did not present any significant differences between the two groups of patients. However, cell cycle did seem to have a very different prognostic value for adults and for children. G2 + M was a strong prognostic indicator for childhood ALL: duration of CR and survival were significantly longer when G2 + M was higher (P less than 0.01). In adults, survival was longer for intermediary (between 3.8 and 5.8%) and high (over 7.2%) G2 + M values (P less than 0.01). The negative correlation between S and G2 + M observed in adults and the absence of correlation in children raise the possibility of differences in duration of the different phases for the two groups and perhaps an accumulation of cells in G2 or tetraploidy in some cases. PMID- 2930707 TI - An association between parameters of liver blood flow and percentage hepatic replacement with tumour. AB - The extent of hepatic replacement with tumour is a significant prognostic factor in patients with liver metastases. Measuring the percentage hepatic replacement (PHR) accurately is difficult, but is important for both patient management and clinical trial evaluation. This study correlates haemodynamic indices obtained by dynamic liver scintigraphy (DLS) with estimates of PHR made from isotope scan, ultrasound, CT scan and laparotomy in 45 patients with established colorectal liver metastases and 21 controls who also underwent DLS. There was a significant reduction in the mesenteric fraction (MF) in the group of patients with metastases compared to the controls (P less than 0.001), and also a significant trend for progressive reduction in the MF with increasing PHR. A significant rise in an index of total hepatic arterial blood flow was also demonstrated with increasing PHR. These results are important with current interest in regional hepatic arterial therapy, and may prove of clinical value for prediction or monitoring of response to therapy. PMID- 2930708 TI - Predictors of hormone response for patients with ER-unknown breast tumours. AB - Characteristics of cells that are associated with the hormonal dependence of tumours are described, and it is shown that clonogenicity and hormone-induced proliferative response of breast tumours are as good markers of hormonal dependence as is oestrogen receptor. Thus tumours that formed less than 150 colonies per 500,000 cells seeded and that increased their proliferative activity 1.8-fold or more in response to hormones were the tumours that were likely to respond to endocrine treatments, whereas all other tumours were likely to be refractory to endocrine treatments. These two criteria (clonogenicity and proliferative response to growth hormones) correctly identified the response to subsequent endocrine treatments in 15 out of 17 patients with oestrogen receptor unknown tumours. It is proposed that they may constitute a substitute for the oestrogen receptor status in patients with non-biopsiable tumours, and an additional discriminant where the oestrogen receptor assay is available. PMID- 2930709 TI - Determination of oestrogen receptors with monoclonal antibodies in fine needle aspirates of breast carcinoma. AB - Fifty patients with operable breast carcinoma underwent fine needle aspiration for cytological examination. The smears were prepared by means of the immunocytochemical method using monoclonal antibodies for the determination of the oestrogen receptors (ER). After surgery the contents of the ER were determined with the traditional biochemical technique. The results of the immunocytochemical method showed 31 positives, two of which disagreed with the biochemical results, 15 negatives and four cases which could not be assessed due to the absence of adequate numbers of cells. The ICA staining for ER was expressed on a semiquantitative basis; there was a significant correlation between this and the values expressed by the biochemical technique, with a coefficient of 0.83, P less than 0.000006. PMID- 2930710 TI - Squamous carcinoma of the oesophagus: histological criteria and their prognostic significance. AB - One hundred resected cases of squamous cell carcinomas of the oesophagus were reviewed and a series of histological criteria related to the survival time. Two histological features were important in the assessment of survival. Good prognostic factors were a marked lymphocytic response to the tumour and a lack of intravenous tumour infiltration. Presence of tumour in the middle third of the oesophagus, infiltration through the muscularis propria, severe tumour necrosis, glandular or small cell tumour differentiation, lymphatic invasion and lack of peritumoural fibrosis were all factors which tended to worsen prognosis. None of these factors reached statistical significance. The degree of squamous differentiation had no effect on survival. PMID- 2930711 TI - Aetiology of oral cancer in patients less than or equal to 30 years of age. PMID- 2930712 TI - Prognostic factors in a T3 bladder cancer trial. Co-operative Urological Cancer Group. AB - Information on primary tumour size, status of the pelvic lymph nodes, histological type and macroscopic tumour appearance, as well as age and sex, was available at presentation for 394 patients in the Co-operative Urological Cancer Group's prospective randomised trial for T3 cancer of the urinary bladder. An apparently significant prognostic effect of age and sex was shown to be entirely consistent with the effect of natural mortality. Primary tumour size was found to be the single most powerful prognostic factor (P = 0.002), followed by nodal status (P = 0.02). These factors do not act independently. Multivariate analysis showed that 75% of the effect of all the six variables and their first order interactions could be explained by a single prognostic grouping based on tumour size and nodal status only. Three levels for this grouping are proposed: node negative small tumour, node-negative moderate tumour and either node-positive or large tumour. The 3-year survival probabilities for the three prognostic groups were 85.7% (95% CI 57.2 and 96.4%), 60.3% (48.0 and 71.5%) and 33.3% (23.5 and 44.8%) respectively. PMID- 2930713 TI - Endometrial cancer and patterns of use of oestrogen replacement therapy: a cohort study. AB - 5,160 non-hysterectomised women aged 44-100 years completed a health survey questionnaire as part of a longitudinal study of a southern California retirement community begun in June 1981. As of 1 January 1987, 50 incident cancers of the endometrium had occurred among these women, who had contributed 23,786 years of follow-up. Women who had used oestrogen replacement therapy had a relative risk of endometrial cancer of 10 compared to women who had never used oestrogens (P less than 0.0001). Risk increased with increasing duration of use (chi 2 test for trend = 50.60, P less than 0.0001); women who had used oestrogens for 15 or more years had a relative risk of 20 (95% C.I. = 7.2, 54) compared to non-users. While current and recent users (i.e. those who had used oestrogen within one year of the initial survey) had the greatest risk (RR = 25, 95% C.I. = 9.2, 69), women who had last used oestrogens 15 or more years ago still had a significantly increased risk (RR = 5.8, 95% C.I. = 2.0, 17). No other variable studied had a major effect on risk, except smoking. Women who smoked at the time of menopause had a significantly reduced risk of disease (RR = 0.38, P = 0.005), which was essentially unchanged after adjustment for oestrogen use. PMID- 2930714 TI - Long-term risk of second malignant neoplasm after a cancer in childhood. AB - The risk of subsequent second malignant neoplasm was studied in a cohort of 634 patients, treated for a childhood cancer at the Gustave Roussy Institute between 1942 and 1969, and in complete remission five years after diagnosis. The most frequent types of first primary cancers (FPC) were Wilms' tumours (28% of the children), neuroblastomas (16%), lymphomas (12%) and soft tissue sarcomas (11%). Median follow-up duration after FPC was 19 years. Thirty-two patients (obs = 32) developed a total of 35 second cancers. Bone, thyroid, connective tissues and skin were the most frequent types of second cancer, with six patients for each type. The average annual incidence of second cancer was 0.36%. The average annual incidence for the periods 5-9, 10-14, 15-19, 20-24 and 25+ years after FPC was respectively 0.16%, 0.34%, 0.36%, 0.71% and 1.18%. The cumulative incidence of second cancer for the periods 5-20, 5-25 and 5-30 years after FPC was, respectively, 4.3% (95% CI: 2.8-6.6%), 7.8% (95% CI: 5.1-11.8%) and 13.0% (95% CI: 8.2-20.0%). The expected number of cancers in the cohort, computed from Danish cancer incidence data, was exp = 2.2. When compared to this expected number, the average annual excess incidence of second cancer, defined as obs-exp divided by the number of person years of observation, was 0.33%. This rose from 0.15% for the period 5-9 years after FPC to 1.09% for the period beginning 25 years after FPC. The standardised incidence ratio of second cancer (i.e. obs/exp) was 15 (95% CI: 10-21), and was fairly constant in the period extending from 15 to 20 years after FPC diagnosis. Obs/exp was equal to 25 for the patients who had had chemotherapy and equal to 9 for those who had not. Cyclophosphamide seemed less carcinogenic than the other alkylating agents. Obs/exp was similar for the patients who had received radiotherapy and for those who had not. The risk of cancer increased with age in the reference population and increased faster in the cohort, because the standardised incidence ratio is constant over a long period. PMID- 2930715 TI - Oral contraceptives and primary liver cancer. PMID- 2930716 TI - Arginine vasopressin--a mediator of chemotherapy induced emesis? AB - Concentrations of plasma arginine vasopressin (AVP) were studied in patients receiving chemotherapy. Of the 18 patients studied, nine experienced nausea and vomiting and the remaining nine were nonvomiters who suffered at worst mild nausea. Plasma AVP in the non-vomiting group remained within the normal range (0.5-1.5 pmol 1(-1] throughout the sampling period. However, patients who vomited showed (with one exception) substantial rises in AVP ranging from 4 to 129-fold. Plasma AVP concentrations were outside the normal range in vomiters and were higher than in non-vomiting patients at 3 h (P less than 0.05) and 5h (P less than 0.01) after chemotherapy. One patient was sampled during consecutive treatment courses, once as a vomiter and once as a non-vomiter; results demonstrated a 16-fold rise in AVP as a vomiter and no rise as a non-vomiter. Significant changes in plasma AVP levels were also observed in patients who suffered moderate or severe nausea compared to those who had mild or no nausea (P less than 0.05). Plasma AVP may prove to be a good objective marker for nausea in future anti-emetic trials. PMID- 2930717 TI - Phase I study of 21 days continuous infusion with vindesine. PMID- 2930718 TI - Geographical variation in mortality from leukaemia and other cancers in England and Wales in relation to proximity to nuclear installations, 1969-78. AB - The distribution of mortality from 11 causes of death (lymphoid leukaemia, other leukaemia, leukaemia of all types, Hodgkin's disease, other lymphomas, all lymphomas, multiple myeloma, lung cancer, other malignancies, all malignancies and all other causes) has been examined in three age groups throughout England and Wales over the period 1969-78. The reorganisation of local authority administration in 1974 meant that the smallest areas that could be examined were 400 county districts or (in some cases) approximate county districts formed by aggregating pre-1974 local authority areas. The variation in the numbers of deaths observed about the numbers expected was assessed using log-linear models to estimate the effect on the relative risk in each district associated with social class, rural status, population size, health authority region and proximity to one of 15 nuclear installations. Trends in risk with increasing proximity to an installation (as judged by the proportion of the population resident within 10 miles) were examined after adjustment for the other four variables. The results showed that in districts near to an installation there were significant excess mortalities in persons under 25 years of age from leukaemia (RR = 1.15, P = 0.01) and especially from lymphoid leukaemia (RR 1.21, P = 0.01) and from Hodgkin's disease (RR 1.24, P = 0.05) and a significant deficiency of mortality from lymphoid leukaemia in persons aged 25-64 years. No significant trends were observed with an increasing proportion of the population near to the installations and the greatest excess mortality from lymphoid leukaemia in young persons was observed in the districts with the intermediate proportion of the population (10.0-65.9%) near an installation. PMID- 2930719 TI - Primary thrombocythaemia: diagnostic criteria and a simple scoring system for positive diagnosis. AB - Forty new patients with elevated platelet counts (greater than 600 x 10(9)/l) and without palpable splenomegaly were assigned to diagnostic groups defined by essentially conventional criteria after 3 months follow up: Proliferative (17), reactive (17) or unclassified (six). Mean platelet volume (MPV), platelet distribution width (PDW), platelet nucleotide ratio (ATP:ADP), unstimulated BFU-E derived colony formation from peripheral blood, spleen scan and clinical ischaemia were assessed at the outset, with a view to defining diagnostic criteria for distinguishing primary thrombocythaemia from reactive thrombocytosis. All except the first variable were significantly associated with diagnostic group (P less than 0.05). A simple scoring system was devised: enlarged spleen on scan, or presence of BFU-E, each scored 2; elevated PDW (greater than 2 SD from mean), elevated ATP:ADP (greater than 4 SD from mean) or presence of clinical ischaemia, each scored 1. Score totals greater than or equal to 3 predicted primary thrombocythaemia, and totals less than 3 suggested reactive thrombocytosis (predictive value 89%). The system correctly predicted diagnosis in four out of four (probably six out of six) patients whose diagnosis was not apparent initially, and thus whose results were not used in constructing the scoring system. Exclusion of BFU-E from the system resulted in only one incorrect prediction in this group. PMID- 2930720 TI - Duration of first remission as an indicator of long-term survival in chronic myelogenous leukaemia. AB - Approximately 31 patients with chronic myelogenous leukaemia (CML) are documented in the literature who survived more than 10 years after diagnosis. We present a CML-patient whose survival of 27 years is probably the longest reported so far. The analysis of the course of disease in these patients revealed that the duration of unmaintained first remission after chemotherapy is of high prognostic significance. In 17 of 24 evaluable patients the remission lasted more than 1 year and in another five at least 6 months (mean 73.8 months, range 0-240 months). In most patients busulfan was used as initial therapy. There was no correlation between the amount of drug given and the duration of remission or survival. Other parameters such as sex, age, initial leucocyte counts, differential count, haemoglobin, platelet count or spleen size seemed to have no prognostic relevance. While approximately 25% of CML patients with typical duration of survival exhibit a Ph1 chromosome mosaicism only, this finding was present in nearly half of the long-term survivers. PMID- 2930721 TI - Spontaneous programmed death (apoptosis) of B-chronic lymphocytic leukaemia cells following their culture in vitro. AB - When B-chronic lymphocytic leukaemia (B-CLL) cells derived from peripheral blood were cultured in vitro, a substantial proportion of them spontaneously died by apoptosis. This type of cell death is morphologically and biochemically distinct from necrosis and has previously been found to occur under physiologic and certain pathologic conditions where cell deletion appears controlled and biologically meaningful. By 30 h of culture, approximately 20% of the unfractionated B-CLL cells were affected. There was no significant difference in the incidence of apoptosis in T-cell depleted and undepleted cultures or when either autologous or normal human serum was used. Furthermore, seeding densities of 2 x 10(6) and 5 x 10(5) cells/ml resulted in a similar incidence of apoptosis, indicating that cell density was unlikely to be a contributing factor in producing the death. The finding that B-CLL cells spontaneously die in vitro has at least two important implications. Firstly, previous work relating to some of the functions of B-CLL cells and their interactions with T cells may require re evaluation. Secondly, an understanding of the mechanisms involved in the induction of apoptosis in this disease may have therapeutic consequences. PMID- 2930723 TI - Decline of blood haemoglobin in the aged: a longitudinal study of an urban Swedish population from age 70 to 81. AB - Blood haemoglobin (Hb) and related components were determined in a representative sample (n = 973, 449 men and 524 women) of a 70-year-old population, reinvestigated at age 75, 79 and 81. At age 81, 145 men and 259 women remained in the study. Longitudinal analysis demonstrated a significant decline in Hb concentration with advancing age, in the total study groups as well as in subsamples remaining after exclusions due to disease. The mean annual decline from age 70 to 81 in a subsample without definable disorders was in men 0.063 g/dl, in women 0.035 g/dl. There was a similar decline among subjects with high, intermediate or low Hb concentrations during the study. Only part of the observed intraindividual variations could be explained by factors other than age. PMID- 2930722 TI - Burkitt cell acute leukaemia (L3 ALL) in adults: a report of 18 cases. AB - Between 1981 and 1987, L3 ALL was diagnosed in 18 adult patients, with a median age of 26 (range 16-66) and M/F ratio of 3.5. At diagnosis, 11 patients had splenomegaly, 11 had enlarged lymph nodes, and 15 patients had central nervous system (CNS) disease, of whom 10 had mental neuropathy. Anaemia was found in 13 patients, thrombocytopenia in 17 and the median white cell count was 25.5 x 10(9)/I (range 8.6-89). Surface immunoglobulins were found on the blasts of every patient. Seventeen patients had a t(8;14) (q24;q32) translocation. One had an apparently normal karyotype, but only six mitoses could be examined. During the period of the study different treatment protocols, which comprised increasingly intensive systemic and CNS chemotherapy, were used. Six patients died less than 3 weeks after admission, two of them of acute tumour lysis syndrome and two of CNS haemorrhage. In two other patients, rapid progression of CNS leukaemia was seen in spite of the treatment. Ten patients (56%) achieved complete remission (CR). Two were allografted and two were autografted early in CR. Four patients relapsed, three of the four relapses involving the CNS. A median actuarial disease-free survival was not attained, and a plateau was achieved at 57% after 7 months, with no later relapse. Median actuarial survival of the 18 patients was only 6 months, but a plateau was obtained at 31% after 11 months. Prognosis seemed related to the intensity of chemotherapy: recent patients, treated more aggressively, achieved CR more often than earlier patients, treated with less intensive protocols, although the number of patients was too small to draw any firm conclusion. The initial white cell count was also a prognostic factor, as none of the patients with more than 30 x 10(9)/I leucocytes achieved CR. Our results suggest that the outcome of adult L3 ALL can be improved, as in children, by increased intensity of treatment, particularly with regard to CNS leukaemia therapy. Early deaths are still frequent, however, but their incidence can probably be reduced by better prevention and early management of the acute tumour lysis syndrome. PMID- 2930724 TI - A new doubly substituted sickling haemoglobin: HbS-Oman. PMID- 2930725 TI - Respiratory input in inhalation experiments. AB - The definition of the respiratory input in experimental human exposure to volatile solvents was examined on theoretical grounds. The respiratory rate of input may be defined as the rate of uptake that equals the inhaled minus exhaled amount per minute. In the present paper the rate of respiratory input is defined as the rate of the functional intake (RFI) which equals the product of the inhaled concentration (CI) and a functional alveolar ventilation (Va). The functional Va is a virtual alveolar volume per minute which equilibrates completely with the mixed venous blood. Human subjects were exposed simultaneously to tetrachloroethene (PER, perchloroethylene) and trichloroethene (TRI) in order to study the consequences of the application of both definitions. It is shown that when using the uptake as the respiratory input some misleading conclusions may be drawn on (a) the dependence of the metabolised fraction on the duration of exposure, (b) the dependence of the kinetic characteristic on the duration and route of administration, and (c) the changes of the rate of metabolism during exposure due to physical exercise. The respiratory input defined as the rate of functional intake (RFI) rejects these misleading conclusions. PMID- 2930726 TI - Ultrastructural changes of the peripheral nerve induced by vibration: an experimental study. AB - To investigate the effects of vibration on the peripheral nerves, rabbits were exposed to vibration of 60 cycles/s frequency with 0.35 mm amplitude (acceleration: 51 m/s2) for two hours daily. After 150, 250, 450, and 600 hours vibration, thin sections of the saphenous and median nerves were examined under the electron microscope. Vibration was found to induce the following changes: (1) disruption of the myelin sheath and constriction of the axon, (2) accumulation of vacuoles in the nodal gap and paranodal region, (3) disorganisation of the paranodal end loops and detachment of the paranodal end loops from the axolemma, (4) dilatation of the Schmidt-Lanterman incisures (SLI) and increased density of SLI, and (5) disappearance of neurotubules and neurofilaments in axons. The diameters of myelin sheaths disrupted by vibration varied from 2 to 12 microns. The extent of the myelin disruption is proportional to the vibration dose. PMID- 2930727 TI - Hair chromium as an index of chromium exposure of tannery workers. AB - The use of hair chromium (Cr) concentrations as an index of Cr exposure of tannery workers was investigated. As has been shown earlier, Cr from Cr III compounds used in the leather tanning industry is absorbed because concentrations of Cr in serum and urine of tannery workers are significantly increased compared with corresponding concentrations for unexposed controls. Hair samples were collected from 71 male tannery workers from four southern Ontario tanneries and from 53 male controls not exposed to Cr in the workplace. Subjects were matched for age, race, and socioeconomic status. Hair samples were washed, ashed in a low temperature asher, and analysed by flameless atomic absorption. The median hair Cr concentrations for the tannery workers (551 ng/g) was significantly higher (p = 0.0001) than for the controls (123 ng/g). For the tannery workers, hair Cr concentrations were positively and significantly correlated with serum Cr (r = 0.52, p less than 0.01) and with the preshift and postshift urinary Cr/creatinine ratios (r = 0.43, p less than 0.01; r = 0.64, p less than 0.01, respectively). These data indicate that trivalent Cr absorbed from leather tanning compounds results in raised concentrations of Cr in hair and that hair Cr concentrations may be used as an index of industrial Cr exposure. PMID- 2930728 TI - Lung cancer in the meat industry. AB - Routine statistics of occupational mortality and incidence of cancer have consistently shown high rates of lung cancer in butchers. Possible explanations include infection by carcinogenic papilloma viruses, exposure to polycyclic aromatic hydrocarbons and nitrites in the preservation of meat, or a confounding effect of tobacco. To explore these possibilities, we have examined the mortality of 1610 men employed at three British companies processing pork, beef, lamb, bacon, and other meat products. The overall death rate was less than in the national population (271 deaths observed, 310 expected) but there was an excess of deaths from cancer (87 observed, 80 expected), and in particular from lung cancer (42 observed, 32 expected). The risk of lung cancer was concentrated in subjects exposed to recently slaughtered meat, especially after an interval of 10 or more years. These findings increase suspicions of a risk of lung cancer in butchers, although further information is needed about smoking habits in the meat industry. If there is a hazard infection by a papilloma virus would seem the most likely cause. PMID- 2930729 TI - Mortality from asthma and chronic obstructive pulmonary disease among workers in a soft paper mill: a case-referent study. AB - In a case-referent study encompassing 33 cases and 228 referents the potential risk for asthma and chronic obstructive pulmonary disease and respiratory cancer among workers in a soft paper mill was evaluated. The cases were selected from registers of deaths and burials in the parishes around the paper mill. Information on exposure was obtained from the personnel register of the mill but because of shortage of information the cases could only be classified as "exposed" or "non-exposed." At some places in the mill the concentrations of paper dust had previously been high, 10-30 mg/m3. Employment at the paper mill was found to be associated with an increased risk of bronchial asthma and chronic obstructive pulmonary disease (odds ratio = 3.8, p less than 0.05). PMID- 2930730 TI - Work in pregnancy and birth weight for gestational age. AB - In a recent report on prematurity and work in pregnancy based on the Montreal survey noteworthy increases in both preterm births (less than 37 weeks) and infants of low birth weight (less than or equal to 2500 g) were found in women in certain specific occupations or whose work entailed heavy lifting, shift work, long hours, or great fatigue. Because of the large overlap between preterm births and low birth weight, the latter was further analysed with allowance for gestational age in order better to separate factors retarding fetal growth from those shortening gestation. The association of low birth weight with specific occupations, long working hours, and fatigue largely disappeared, suggesting that the effect of these factors was to shorten gestation. By contrast, the association with lifting heavy weights and with shift work persisted, suggesting that these factors retarded fetal growth as well as increasing the risk of preterm birth. PMID- 2930731 TI - Is the short term limit value for sulphur dioxide exposure safe? Effects of controlled chamber exposure investigated with bronchoalveolar lavage. AB - Bronchoalveolar lavage (BAL) which has not previously been used in investigating the effect of sulphur dioxide (SO2) on the human lung was performed on 12 subjects before and after controlled chamber exposure with SO2 for 20 minutes. BAL fluid 24 hours after exposure with 10 mg SO2/m3 (4 ppm, 10 subjects) showed increased alveolar macrophage activity as judged by an increase in lysozyme positive macrophages. Twenty four hours after 20 mg/m3 (4 subjects) a further increase was seen, which was accompanied by an increase in total numbers of macrophages and lymphocytes. Seventy two hours after exposure (4 subjects) cell numbers had virtually returned to pre-exposure levels. These previously uninvestigated reactions indicate potentially noxious effects of SO2 in the lungs at exposure levels that are regarded as relatively safe. PMID- 2930732 TI - Steroid hormone sulphation in lead workers. AB - The metabolism of steroid hormones has been investigated in 10 workers exposed to lead and in 10 non-exposed subjects to determine whether lead interferes with the first or second phase reactions of steroid hormone biotransformation, or both. In the exposed workers blood lead concentrations (PbB) ranged from 45 to 69 micrograms/100 ml; in the controls PbB was less than 25 micrograms/100 ml. No statistical differences were found for the total amount of the urinary hormone metabolites, but a drop of about 50% was observed for the sulphated portion. It is suggested that lead interferes with the mechanisms of sulphoconjugation through an effect on the cytosol enzymes sulphotransferase and sulphokinase. PMID- 2930733 TI - Health hazards of firefighters: acute pulmonary effects after toxic exposures. AB - As part of an environmental monitoring and medical surveillance programme to evaluate potential health hazards from firefighting, complete baseline medical examinations were performed on a cohort of 77 firefighters. During a ten day study period, 37 follow up medical examinations were performed after exposure to fire to monitor any significant differences in pre-fire and post-fire physiological indices, including pulmonary function and blood counts and chemistries. For the group as a whole, no significant differences were found. For individuals not wearing respiratory protective equipment, however, statistically significant post-fire decrements in FEV1 and FVC were noted. These decrements were consistent with previously shown levels of exposure to pulmonary toxicants in this cohort. These results support the need for more extensive use of respiratory protective equipment by firefighters. PMID- 2930734 TI - Twinning in human populations and in cattle exposed to air pollution from incinerators. PMID- 2930735 TI - Reducing late abortions. PMID- 2930736 TI - Transmission of human immunodeficiency virus by heterosexual contact with reference to antenatal screening. AB - Twenty-seven women all of childbearing age, eight of whom were pregnant, were identified as human immunodeficiency virus (HIV-1) antibody positive in the genitourinary medicine clinics of East Riverside up to March 1987. Of these 27 women 11 had acquired the virus by heterosexual contact. Between 1 March 1987 and 29 February 1988, all 1328 women attending the antenatal clinic were offered an HIV screening test, 982 accepted and the other 346 declined to be tested. Two of the 982 tested women were found to be HIV-1 antibody positive. Two other pregnant HIV-1-positive women were identified during this time, one was tested in the genitourinary medicine clinic and the other whilst an in-patient for drug withdrawal. All except one of the 12 HIV-1-antibody-positive pregnant women were in known high-risk groups. In addition up to March 1988, 32 heterosexual men were identified as HIV-1 antibody positive and 22 of these were intravenous drug abusers. If the present trend continues, more women will become infected, often unaware that they are at risk and this may not be detected unless HIV testing is offered to all pregnant women and widely accepted. Decisions on local policy should be based on the available estimates of prevalence of HIV infection in that community. PMID- 2930738 TI - Variation in the T/QRS ratio of fetal electrocardiograms recorded during labour in normal subjects. AB - The T/QRS ratio of the fetal ECG was obtained during labour from 25 women with normal pregnancies. The poor signal-to-noise ratio of the unprocessed signals, chiefly due to baseline wander, led to a wide variation between individual measurements. This problem was overcome by data averaging, the ratio being expressed as a mean over 1-min epochs. The average T/QRS ratio of each labour record ranged from 4% to 23% with a mean of 10% (for all 25). The average range (between 5th and 95th centile) of the 1-min T/QRS ratios was 13% and there were no significant changes as labour progressed. The effect of contractions on the T/QRS ratio was measured from eight subjects and found to be inconsistent. PMID- 2930737 TI - Congenital human immunodeficiency virus (HIV) infection in the Bahamas. AB - In the 13-month period between June 1985 and July 1986, 27 children were found to be HIV positive in the Princess Margaret Hospital in Nassau. Nineteen of the children had clinical AIDS, four were in the prodromal phase and four were symptom free. The clinical course of these infants is presented. Of the 18 mothers 16 were screened and were all seropositive and asymptomatic. They remained healthy in spite of subsequent pregnancies in nine of them (56%) during a follow-up period of between 13 and 65 months (mean 40 months). Fifteen of the 18 mothers were Haitian but only three had other risk factors, throwing doubt on the value of selective screening in Afro-Caribbean countries. PMID- 2930739 TI - Umbilical artery flow velocity waveforms in labour. AB - Doppler signals were recorded from the umbilical arteries in 103 women during labour. The pulsatility index (PI) did not alter with progress in labour. During uterine contractions the PI showed a change only if there was a deceleration in the fetal heart rate. Low birthweight (less than 10th centile) and delivery by caesarean section for fetal distress were significantly more frequent in patients with abnormal PI values (defined as greater than 2 SD above the mean in normal labours). Fetal scalp blood pH was measured in 24 patients. The PI was abnormal in only one case, but none of the 24 had a pH less than 7.20. PMID- 2930740 TI - Maternal weight, weight gain and birthweight at term in the rural Tanzanian village of Ilula. AB - In an area-based study in a rural Tanzanian village, the relations of maternal weight and weight gain during pregnancy to birthweight were analysed for 331 term deliveries. The distribution of body-mass index, used as an indicator of maternal nutritional status, was similar to the pattern seen in Sweden, although mean maternal height (156 cm) was 9 cm below that of Swedish women. Mean initial weight measured at week 14 was 53 kg and total pregnancy weight gain was 6 kg. Women weighing greater than or equal to 60 kg in early pregnancy gained less weight (0.16 kg/week) than those weighing less than 50 kg (0.22 kg/week). Birthweight was correlated both with maternal weight in early pregnancy and with weight gain during pregnancy, but only 10% of the variation in birthweight was explained by these maternal factors. Mean maternal weight 24 h postpartum was equal to the weight at 14 weeks of pregnancy, implying, on the average, no net weight gain. Women with a positive net weight gain had heavier babies than women with a negative net weight gain. Maternal anthropometric characteristics are important underlying determinants of intrauterine growth and birthweight, but they explain only a minor part of the variation and are of little value for screening purposes in individual women. PMID- 2930741 TI - Tocolysis during cervical ripening with vaginal PGE2. AB - Forty-two primigravidae with unripe cervices (modified Bishop score less than or equal to 5) were pretreated with 8 mg of oral salbutamol 30 min before vaginal administration of 5 mg of PGE2. The proportion of patients in established labour after treatment (19%) was markedly less than results reported previously and cervical improvement occurred in 86% of the non-labouring patients. The improved outcome of labour associated with the prior administration of PGE2 when the cervix is unripe, including reduced induction-to-delivery intervals and higher rates of vaginal delivery was maintained. Apart from some minor side-effects, there were no adverse effects noted as a direct consequence of the tocolytic; blood loss was not increased, although one patient suffered an intrapartum abruption. This approach allows a greater control of induced uterine activity and timing of delivery which may be of particular importance in women with suspected placental insufficiency. PMID- 2930742 TI - Vaginal pH in pregnancy in women delivered at and before term. AB - A microelectrode was used to measure vaginal pH in a longitudinal study during pregnancy in 30 women, 28 of whom were delivered at term. Excluding pH readings made in the presence of pathogenic organisms, 120 readings were taken. The mean vaginal pH of all subjects was 4.16 (SD 0.41). Analysis of variance showed no significant within-subject variation of pH during pregnancy. Two women had spontaneous preterm deliveries (less than 37 weeks) and their mean vaginal pH during pregnancy was 5.05 and 5.06. Eight women admitted in preterm labour, who then gave birth, had a mean pH of 5.43 (SD 0.94) which was significantly higher than the mean pH of 10 women in labour at term (4.58, SD 0.59). The relation between bacterial growth in vitro and the surrounding pH was also examined. Escherichia coli, a potential pathogen, behaved differently from both Lactobacillus (a commensal organism) and Candida albicans. The clinical observations show a trend towards higher vaginal pH values in association with preterm labour. PMID- 2930743 TI - Maternal and paternal alcohol consumption and miscarriage. AB - To explore the role of parental alcohol consumption in miscarriage we interviewed 80 women who miscarried about their own and their partners' drinking habits. A control group of 81 gestational-age-matched women whose pregnancy ended in the delivery of a healthy infant at term were similarly questioned. The use of alcohol by women and men was equally frequent in both groups. Before pregnancy, the mean alcohol consumption per week had been about 1-2 drinks for the women and 4-5 drinks for the men. During the presumed day of conception, 13% of the women who miscarried and 11% of the women in the control group had drunk on average 3-4 drinks; the other women had been abstinent at this time. Of the partners, 13% and 15%, respectively, had taken a mean of 4-5 drinks. In both groups 58% of the subjects continued to consume alcohol during pregnancy. The mean consumption was about one drink a week by the women who miscarried and half a drink a week in the control group. Of women who miscarried, 36 had a blighted ovum and in this subgroup alcohol consumption in both women and men was similar to that in the other women who miscarried and their partners, suggesting that alcohol is not causally related to the development of a blighted ovum. These results suggest that moderate maternal or paternal alcohol consumption does not increase the risk of miscarriage. PMID- 2930744 TI - Atopy in couples with unexplained infertility. AB - In an initial exploratory study, proneness to atopy was measured by specific allergen history, allergen skin testing and plasma IgE in couples with unexplained infertility and in a comparison group of couples who had recently had a child. At least one of the assessments was positive in 29 out of 47 infertile couples and in 52 out of 103 controls, but only five of the infertile group and two of the fertile group had all three assessments positive. Raised IgE levels occurred significantly more often in the infertile couples than in the comparison group. PMID- 2930745 TI - A clinical and urodynamic study comparing the Stamey bladder neck suspension and suburethral sling procedures in the treatment of genuine stress incontinence. AB - Twenty women with urodynamically proven genuine stress incontinence were randomly allocated to treatment by suburethral sling or Stamey endoscopic bladder neck suspension. Urodynamic assessment was performed before and 3 months after surgery; clinical follow-up is reported up to 2 years. Blood loss was greater, and there were significantly more postoperative complications associated with the sling procedures. The subjective and objective cure rates at 3 months and 2 years were not significantly different between the two procedures. No significant changes in the resting urethral pressure profile were evident, although with both procedures, cure was associated with an enhancement in pressure transmission ratios in the proximal urethra. Detrusor instability occurring for the first time after operation was associated with both procedures; the sling, in addition, induced a significant degree of outflow obstruction, although this was not evident after the Stamey procedure. PMID- 2930747 TI - Tuberculous meningitis in pregnancy. AB - Four women with tuberculous meningitis in association with pregnancy are described to illustrate both the serious nature and varied presentation of this condition. Mortality or neurological morbidity may occur more frequently during pregnancy, but in general correlate closely with delay in diagnosis and initiation of appropriate therapy. Treatment often needs to be started empirically, and neurosurgical intervention may prove life saving. PMID- 2930746 TI - Genital cancer among wives of men with penile cancer. A study between 1958 and 1982. AB - Previous studies have suggested an association between penile cancer and cervical cancer but the results have been difficult to interpret. The current study includes 1064 cases of penile cancer reported to the National Swedish Cancer Registry between 1958 and 1980. One matched control for each living case was chosen randomly from the Swedish Population Registry, and for cases who had died, from the National Death Registry. Details about the men, their marriages and each wife or wives were obtained from the population registry in the parish in which the men lived or had died. The personal identification number and name of each wife or wives were matched against the cancer registry. All genital cancers, including 15 cervical cancers, were distributed equally among the wives of the cases and those of the controls. The expected rate of cancers among the population of wives of cases was also calculated and there was no difference between the observed and the expected number of women with cancer. The results did not show an association between penile cancer in men and cervical cancer in their sexual partners. PMID- 2930748 TI - Ovarian fibromatosis with minor sex cord elements. Case report. PMID- 2930749 TI - Alternative vacuum supplies for ventouse deliveries. PMID- 2930750 TI - Tuberculous peritonitis in pregnancy. A follow-up. PMID- 2930751 TI - Occult biochemical pregnancy: fact or fiction? PMID- 2930752 TI - Retrieval of intrauterine contraceptive devices with missing tails, using Lamicel. PMID- 2930753 TI - Uteroplacental and umbilical artery blood velocity waveforms in placental abruption assessed by Doppler ultrasound. PMID- 2930754 TI - Dehydrational crises: a major risk factor in blinding cataract. AB - An earlier case control investigation has indicated a strong relationship between dehydrational crises and risk of presenile cataract. A second methodologically distinct case control study of risk factors in cataract has been carried out in a population very different in terms of environmental and sociocultural characteristics from the population investigated in the earlier study in Central India. The results strongly confirm the findings from the first study and indicate that an estimated 38% of blinding cataract may be attributable to repeated dehydrational crises resulting from severe life threatening diarrhoeal disease and/or heatstroke. The risk of blinding cataract was strongly related to level of exposure to dehydrational crises in a consistent and dose dependent manner, thus indicating a causal association. The findings are discussed in relation to possible sources of bias in the study, confounding in the data, and the steps that were taken to minimise their undesirable effects. PMID- 2930755 TI - Delayed microhyphaema with intraocular lenses: a retrospective study of eight patients. AB - Eight patients with delayed microhyphaema were identified from a computer data base of 1209 patients who had had cataract extraction with Binkhorst 4-loop intraocular lens insertion. Five cases were recurrent. The cases were examined to try and identify an underlying cause. No single cause was identified, but trauma, hypertension, and oral anticoagulants were found to be associated. Some episodes were asymptomatic. The wide variety of surgical technique and style of lens with which this complication has been reported implies multiple causative factors. The source of the bleeding and its management are discussed. PMID- 2930756 TI - Are severe acute retinopathy of prematurity and severe periventricular leucomalacia both ischaemic insults? AB - Over a period of 20 months six preterm infants have been seen who developed severe acute retinopathy of prematurity (ROP) and who also had ultrasound evidence of extensive cerebral parenchymal changes compatible with severe periventricular leucomalacia. Only one of these infants had a birthweight of less than 1000 g, and their gestational ages ranged from 27 to 30 weeks. The association between these two important complications of preterm birth has led us to postulate that an episode of hypoperfusion of the cerebral circulation sufficient to result in cerebral ischaemia could also reduce an already compromised ocular blood flow and further exacerbate retinal ischaemia, thereby increasing the severity of ROP. PMID- 2930757 TI - Photoaversion in retinitis pigmentosa. AB - Photoaversion, or light-induced interference with visual comfort and performance, has been a recognised but poorly documented symptom in retinitis pigmentosa (RP). We found that a majority of our RP patients complained of photoaversion even in the absence of significant cataract. RP patients had reduced contrast sensitivity relative to normal people, but the decrement in their visual performance as a result of glare or photostress was only slight. RP patients had raised short-term adaptation and increment threshold levels, but their rate of short-term or photopic adaptation was normal. Photoaversion in RP may result because a small interference with contrast sensitivity or adaptation can place patients in a range of functional disability, or it may derive from a combination of minor aberrations. PMID- 2930758 TI - Epiblepharon with inverted eyelashes in Japanese children. I. Incidence and symptoms. AB - Epiblepharon commonly occurs in Japanese infants and tends to disappear spontaneously with age. We examined 4449 Japanese children aged 3 months to 18 years for epiblepharon associated with inverted eyelashes touching the cornea. The condition was evident in 441 cases. We found that the incidence of epiblepharon decreased with age, but about 2% of high school students still had the condition. No sexual predilection was found. Lower eyelids were commonly involved bilaterally. Most cases of epiblepharon produced no or mild symptoms. PMID- 2930759 TI - The pattern electroretinogram in glaucoma: an evaluation by relative amplitude from the Bjerrum area. AB - A new concept for evaluating the pattern electroretinogram (PERG) in glaucoma and its clinical application are described. The PERG was elicited by two different stimulus fields, namely, the whole central retinal area with a radius of 18 degrees and the paracentral ring area between the radius of 10 degrees and 18 degrees. The amplitude of the PERG for each stimulus field and the ratio of them were analysed for 30 patients with glaucoma or ocular hypertension. Among these only a small number of eyes were detected as abnormal when we evaluated the amplitude itself either with the central stimulus or the paracentral ring stimulus, whereas the ratio of the two values was below normal in some cases of advanced glaucoma. We conclude that the ratio of the paracentral to central PERG is useful for detecting glaucoma. PMID- 2930761 TI - 123I metaiodobenzylguanidine (MIBG) scintigraphy of retinoblastoma: preliminary experience. AB - 123I metaiodobenzylguanidine (MIBG) is a radiopharmaceutical used for imaging neural crest tumours. The possibility of using 123I MIBG for imaging retinoblastomas has been assessed in this pilot study. Ten patients were studied, nine with clinically and histologically proved retinoblastomas and one with Coats's disease. 123I MIBG scintigraphy correctly identified the neoplasm in eight patients but gave a negative result in two, one of whom had Coats's disease and the other a retinoblastoma which proved to be extensively necrotic on histological examination. These preliminary results suggest that 123I MIBG scintigraphy may have a role in differentiating retinoblastomas from lesions that simulate them. PMID- 2930760 TI - Twenty cases of sympathetic ophthalmia. AB - We reviewed the charts of 20 patients with sympathetic ophthalmia who were seen in the uveitis clinic at the Eye and Ear Infirmary within an 11-year period. Of these 20 patients 14 maintained 20/50 or better visual acuity in at least one eye. We found early enucleation to be associated with a better visual prognosis, possibly due to earlier diagnosis and faster, more aggressive therapy rather than a reduction in antigenic load. The clinical appearance of Dalen-Fuchs nodules appears to indicate a more severe stage of disease. Chlorambucil was useful in patients with severe disease. To be effective and to lessen its side effects chlorambucil was given in daily dosages that were increased weekly over a short period to achieve bone marrow suppression. After a course of chlorambucil therapy intraocular inflammation could be controlled with topical steroids alone. PMID- 2930762 TI - Naturally occurring antibodies to bovine and human retinal S antigen: a comparison between uveitis patients and healthy volunteers. AB - The antibody responses to human and bovine retinal S antigen in the sera of patients with uveitis from various causes were compared with those of a group of healthy volunteers who were fully screened for signs of eye disease. Antiretinal antibodies were found with equal frequency and through the same range of titres in patients and controls, irrespective of the nature or activity of the uveitis. These findings were confirmed by spectrotypic analysis of sera from patients and controls where the predominant serum antibody response was polyclonal. In a small group of patients with retinal vasculitis there was an additional monoclonal response, indicating clonal expansion of a single lymphocyte subset. The prevalence of serum antibodies to retinal antigens in the normal population may indicate a protective role for 'natural' autoantibodies, as has recently been suggested for autoimmune diseases generally. PMID- 2930763 TI - Blind and partial sight registration in Avon. AB - All blind and partially sighted registration forms for the county of Avon for a two-year period were analysed, and the findings are presented. Comparisons with the national figure published by Sorsby over 20 years ago show there has been no marked change in the rates of blind registration per 100,000 population with the exception of those for cataract, which show a large reduction. Diabetic registrations have remained similar, but this may represent an encouraging trend in view of the significant increase in the size of the diabetic population. Glaucoma may show some improvement in the future when time has elapsed for beta blockers and trabeculoplasty to be fully assessed. There has been an increase in the rate of registration from aging macular degeneration. PMID- 2930764 TI - Recent trends in the registration of blindness and partial sight in Leicestershire. AB - A study is reported of all new registrations for blindness and partial sight in the county of Leicestershire, England, for the years 1965, 1975, and 1985. The number of new registrations for blindness has risen considerably over this period, but the increase is shown to be attributable to changes in the age structure of the population and under-registration in 1965. The number of new registrations for partial sight has also increased over the study period but by significantly more than would be expected, even after changes in the population structure are allowed for. The registration rates for Leicestershire when analysed by age, sex, and cause are shown to be broadly in line with available national figures. Registration rates for macular degeneration and glaucoma are increasing in both males and females, and rates for cataract are at a significantly higher level for women than for men. PMID- 2930765 TI - Turnover of 125I-VLDL and 131I-LDL apolipoprotein B in rabbits fed diets containing casein or soy protein. AB - Rabbits fed low-fat, cholesterol-free, semi-purified diets containing casein developed a marked hypercholesterolemia compared to rabbits fed a similar diet containing soy protein (plasma cholesterol 281 +/- 31 vs. 86 +/- 9 mg/dl; P less than 0.05). Turnover studies (three per dietary group) were carried out in which homologous 125I-labeled VLDL and 131I-labeled LDL were injected simultaneously into casein- (n = 8) or soy protein- (n = 9) fed rabbits. ApoB-specific activities were determined in VLDL, IDL and LDL isolated from the pooled plasma of two or three rabbits per dietary group. The production rate of VLDL apoB (1.20 +/- 0.3 vs. 1.09 +/- 0.1 mg/h per kg) was similar for the two dietary groups. The fractional catabolic rate of VLDL apoB was lower for the casein group (0.15 +/- 0.03 vs. 0.23 +/- 0.01.h-1; 0.05 less than P less than 0.10). Although the pool size of VLDL apoB was higher in the casein group (8 +/- 2 vs. 5 +/- 0.3 mg/kg), this value did not reach statistical significance. For LDL apoB, the increased pool size in casein-fed rabbits (30 +/- 5 vs. 5 +/- 1 mg/kg; P less than 0.01) was associated with a decreased fractional catabolic rate (0.03 +/- 0.005 vs. 0.08 +/- 0.008.h-1; P less than 0.01) and a 2-fold increase in the production rate of LDL apoB (1 +/- 0.3 vs. 0.4 +/- 0.06 mg/kg per h; 0.05 less than P less than 0.10) compared to rabbits fed soy protein. Analysis of precursor-product relationships between the various lipoprotein fractions showed that casein-fed rabbits synthesized a higher proportion of LDL apoB (95% +/- 2 vs. 67% +/- 2; P less than 0.001) independent of VLDL catabolism. These results support the concept that the hypercholesterolemia in casein-fed rabbits is associated with impaired LDL removal consistent with a down-regulation of LDL receptors. These changes do not occur when the casein is replaced by soy protein. PMID- 2930766 TI - The rabbit as an animal model of hepatic lipase deficiency. AB - A natural deficiency of hepatic lipase in rabbits has been exploited to gain insights into the physiological role of this enzyme in the metabolism of plasma lipoproteins. A comparison of human and rabbit lipoproteins revealed obvious species differences in both low-density lipoproteins (LDL) and high-density lipoproteins (HDL), with the rabbit lipoproteins being relatively enlarged, enriched in triacylglycerol and depleted of cholesteryl ester. To test whether these differences related to the low level of hepatic lipase in rabbits, whole plasma or the total lipoprotein fraction from rabbits was either kept at 4 degrees C or incubated at 37 degrees C for 7 h in (i) the absence of lipase, (ii) the presence of hepatic lipase and (iii) the presence of lipoprotein lipase. Following incubation, the lipoproteins were recovered and subjected to gel permeation chromatography to determine the distribution of lipoprotein components across the entire lipoprotein spectrum. An aliquot of the lipoproteins was subjected also to gradient gel electrophoresis to determine the particle size distribution of the LDL and HDL. Both hepatic lipase and lipoprotein lipase hydrolysed lipoprotein triacylglycerol and to a much lesser extent, also phospholipid. There were, however, obvious differences between the enzymes in terms of substrate specificity. In incubations containing hepatic lipase, there was a preferential hydrolysis of HDL triacylglycerol and a lesser hydrolysis of VLDL triacylglycerol. By contrast, lipoprotein lipase acted primarily on VLDL triacylglycerol. When more enzyme was added, both lipases also acted on LDL triacylglycerol, but in no experiment did lipoprotein lipase hydrolyse the triacylglycerol in HDL. Coincident with the hepatic lipase-induced hydrolysis of LDL and HDL triacylglycerol, there were marked reductions in the particle size of both lipoprotein fractions, which were now comparable to those of human LDL and HDL3, respectively. PMID- 2930767 TI - Identification of 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholest-24-enoic acid as an intermediate in the peroxisomal conversion of 3 alpha,7 alpha,12 alpha trihydroxy-5 beta-cholestanoic acid to cholic acid. AB - In this study, we have identified a delta 24-unsaturated intermediate involved in the conversion of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid to cholic acid by the peroxisomal fraction of rat liver. An accumulation of this intermediate was observed when NAD+ was omitted from the reaction mixture. The intermediate was isolated by reversed-phase high-pressure liquid chromatography and identified by combined gas-liquid chromatography-mass spectrometry. The peroxisomal fraction was able to catalyze the conversion of the delta 24 unsaturated intermediate to cholic acid in the presence of CoA, ATP, Mg2+ and NAD+. The identification of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholest-24 enoic acid in cholic acid formation supports the proposed reaction mechanism in which the side-chain cleavage of C27-steroids is similar to that of peroxisomal beta-oxidation of fatty acids. This involves an FAD-dependent oxidase acting on 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoyl-CoA. PMID- 2930768 TI - Solubilization, purification and characterization of lysoplasmalogen alkenylhydrolase (lysoplasmalogenase) from rat liver microsomes. AB - Alkenylhydrolase (EC 3.3.2.2; EC 3.3.2.5) has been purified 200-fold to a specific activity of 8.0 mumol/min per mg from rat liver microsomes with 51% of the activity recovered. Purification was accomplished by solubilization of the membrane-associated enzyme with octylglucoside and chromatographic resolution on sequential DEAE cellulose and hydroxylapatite (HPLC) columns in the presence of octylglucoside. The partially purified enzyme, specific for the 2-deacylated plasmalogen, lysoplasmalogen (1-alk-1'-enyl-sn-glycero-3-phosphocholine or ethanolamine), had no hydrolytic activity with intact plasmalogens or 1-acyl-sn glycero-3-phosphoethanolamine. Kinetic analyses of enzymic activity demonstrated apparent Km values of 5.5 and 42 microM for 1-alk-1'-enyl-sn-glycero-3 phosphocholine and 1-alk-1'-enyl-sn-glycero-3-phosphoethanolamine, respectively. The Vmax values were 11.7 and 13.6 mumol/min per mg with the choline and ethanolamine substrates, respectively. The optimal pH range was between 6.6 and 7.1 with both substrates; the energy of activation for the purified enzyme was 15,200 cal. The enzyme required no cofactors and was unaffected by low millimolar concentrations of Ca2+, Mg2+, Mn2+ or EDTA. It was inhibited by the sulfhydryl reacting reagent, p-chloromercuribenzoate. Mono- or diradylglycerophospholipids or sphingomyelin did not affect the enzymic activity at 37 degrees C. Activity of the purified enzyme, destroyed by freezing at -20 degrees C, was preserved if stored at this temperature in the presence of 300-600 microM diradylglycerophosphocholine or 50% glycerol. A continuous spectrophotometric assay, adapted in our laboratory for the assay of liver alkenylhydrolase, facilitated this purification. This is the first reported purification of alkenylhydrolase. PMID- 2930769 TI - Free sphingosines in porcine epidermis. AB - Sphingosines and phytosphingosines serve as intermediates in the synthesis of ceramides and glucosylceramides, which are prominent components of mammalian epidermis. In the present study, we have investigated the possibility that free sphingoid bases also may be present in epidermal tissue. Samples of pig epidermis were trypsinized to separate the stratum corneum from the unkeratinized portion of the epidermis. After drying, the lipids were extracted and analyzed by thin layer chromatography using ninhydrin to detect free amino groups. Both the stratum corneum and the unkeratinized epidermal material contained a ninhydrin positive material with the same mobility as the sphingosine standard. Quantitation of the chromatograms by photodensitometry indicated that free sphingosine bases account for 0.44% by weight of the total stratum corneum lipid and 0.09% of the lipid in the viable portion of the epidermis. To further identify this material, it was treated with 1-fluoro-2,4-dinitrobenzene, which resulted in the production of an intensely yellow N-2,4-dinitrophenyl derivative with the same mobility as N-2,4-dinitrophenylsphingosine on thin-layer chromatography. Oxidation of the isolated dinitrophenyl derivative with lead tetraacetate produced a mixture of aldehydes which were analyzed by gas-liquid chromatography. This analysis indicates that the free sphingoid bases from the stratum corneum consist of a mixture of mainly 16- through 20-carbon sphingenines and sphinganines, the most abundant components being d17:0, d17:1, d18:1 and d20:1. The production of these free sphingosine bases may be significant in regulating epidermal differentiation. PMID- 2930770 TI - The biosynthesis of dehydrodolichyl phosphates by rat liver microsomes. AB - Using improved conditions with rat liver microsomes in the presence of 20% glycerol and 2% Triton X-100 at pH 8.5 it was shown that dehydrodolichyl diphosphate and dehydrodolichyl phosphate were synthesized from isopentenyl diphosphate and farnesyl diphosphate. Small amounts of geranylgeranyl diphosphate and geranylgeranyl phosphate were also formed. The carbon chain lengths of the dehydrodolichyl diphosphate and dehydrodolichyl phosphate were identical (C80 C85). A kinetic study showed that dehydrodolichyl diphosphate formed from farnesyl diphosphate and isopentenyl diphosphate was subsequently hydrolyzed to dehydrodolichyl phosphate. As the concentration of isopentenyl diphosphate was increased from 1 to 50 microM, the chain-length distribution of dehydrodolichyl products shifted from C75-C80 to C80-C85. Addition of MgCl2 into the assay mixture decreased product formation, but did not affect the chain-length distribution (C80-C85). The shift of the chain-length distribution to the same as that observed in naturally occurring dolichol derivatives (C90-C95) was observed when Triton X-100 was omitted from the assay mixture, although deletion of the detergent decreased the enzyme activity. These results, which provide insight into optimal conditions for enzymatic synthesis of the dolichol chain, are discussed in the context of the in vivo pathway for dolichol biosynthesis. PMID- 2930771 TI - The primary structure of human apolipoprotein A-IV. AB - Human apolipoprotein (apo) A-IV was purified from chylous ascites fluid. Proteolytic peptides produced by trypsin and Staphylococcus aureus V8 proteinase digestions were purified by high-performance liquid chromatography and sequenced. Human apoA-IV contains 376 amino acid residues. The peptide-derived sequence generally matches two previously reported DNA-derived amino acid sequences except for discrepancies in five positions. In order to examine these discrepancies further, one complete apoA-IV cDNA clone and another partial clone were sequenced. Comparison of all the available information indicates that the peptide derived sequence reported here is accurate. Sequencing errors probably account for some of the discrepancies between the two primary sequences predicted by earlier nucleotide analyses. In certain positions, however, bona fide sequence heterogeneity or cloning artifact cannot be excluded. PMID- 2930772 TI - Synergistic interaction between vitamin E and the bile pigments bilirubin and biliverdin. AB - The oxidation of soybean phosphatidylcholine (PC) liposomes initiated with a lipid-soluble azo compound within the liposomal membranes has been studied in the absence and presence of membrane-bound vitamin E and water-soluble bile pigments. In the absence of vitamin E, lipid peroxidation proceeded linearly and without delay. Low micromolar amounts of bilirubin ditaurine (BR-DT, a model compound of conjugated bilirubin) or biliverdin (BV) inhibited the oxidation of PC significantly and in a concentration-dependent way. In contrast, neither taurine, ascorbic acid nor reduced glutathione inhibited significantly under these conditions. Both bile pigments were consumed during their protective action. Vitamin E incorporated into the liposomal membranes suppressed the oxidation initially almost completely, thereby producing an induction period. In the combined presence of vitamin E and either of the two bile pigments at 10 microM each, this induction period was increased by at least 200%. In contrast, when 10 microM vitamin E was combined with an equimolar concentration of reduced glutathione, the induction period increased by only about 30%. BR-DT and BV both spared the consumption of vitamin E during the oxidation of PC liposomes. These results demonstrate that conjugated bilirubin and BV located in the aqueous phase can directly scavenge lipid radicals to some extent. Furthermore, both bile pigments can act synergistically with membrane-bound vitamin E to prevent lipid peroxidation initiated in the lipid phase, most likely through regeneration of the vitamin from its chromanoxyl radical. PMID- 2930773 TI - Species pattern of phosphatidic acid, diacylglycerol, CDP-diacylglycerol and phosphatidylglycerol synthesized de novo in rat liver mitochondria. AB - Rat liver mitochondria were incubated with [3H]glycerol 3-phosphate, ATP, CTP and coenzyme A allowing acylatin of glycerophosphate with endogenous fatty acids and the further conversion of labelled phosphatidic acid (PA) to diacylglycerol (DG), CDP-diacylglycerol (CDP-DG) and phosphatidylglycerol (PG). In these glycerolipids, the distribution of label among the individual molecular species was found to be similar, with 16:0-18:1, 16:0-18:2 and 18:0-18:2/16:0-16:0 being the main species. It was concluded that mitochondrial enzymes involved in the de novo synthesis of these glycerolipids exhibited no acyl selectivity for their substrates. The pattern of molecular species of mitochondrial PA, DG and CDP-DG closely approached that of the same glycerolipids synthesized de novo in isolated rat liver microsomes. PMID- 2930774 TI - DNA synthesis by the isolated nuclear matrix from synchronized plasmodia of Physarum polycephalum. AB - Nuclear matrices were isolated from plasmodia of a true slime mold, Physarum polycephalum, and the DNA synthetic activity in vitro was examined. These matrices isolated in S-phase catalyzed DNA synthesis requiring Mg2+, deoxyribonucleoside 5'-triphosphates and ATP, without exogenous templates. The activity changed during S-phase with the rate of in vivo DNA replication. Product analysis by gel electrophoresis revealed that the matrices produced Okazaki fragments. These results suggest that DNA synthesis partially reflects in vivo DNA replication. DNA synthesis was sensitive to aphidicolin, heparin and N ethylmaleimide, indicating involvement of the alpha-like DNA polymerase of Physarum. Exogenous addition of activated DNA stimulated DNA synthesis 4-10-fold and suggested that only some of the existing enzymes are involved in endogenous DNA synthesis. Matrices isolated in G2-phase were also associated with a similar DNA synthetic activity, but they did not produce Okazaki fragments in vitro. It is, therefore, concluded that nuclear matrices are associated with alpha-like DNA polymerase throughout the cell cycle, and that some of the enzymes participate in in vivo DNA replication in S-phase; thus, DNA replication is possibly controlled by this process. The relationship between DNA synthetic activities by the isolated nuclei and matrices was also discussed. PMID- 2930775 TI - Developmentally regulated late mRNAs in the encystment of Physarum polycephalum plasmodia. AB - Physarum polycephalum plasmodia survive adverse conditions by transforming into encysted cells called spherules. In this work we analysed the developmentally regulated mRNAs from the late stages of spherulation. A cDNA library was constructed and four abundant mRNAs were identified. One of the mRNAs was present in trace amounts in early spherules, while the other three were found only in late spherules. A cDNA clone for one of the late spherulation specific mRNAs was sequenced. It codes for a 332-amino-acid protein that did not show significant similarities with any known protein. Since the mRNA for this protein accumulates during spherulation, the protein was called spherulin 4. This protein has many features of a plasma membrane protein; it contains a signal peptide and a long hydrophobic region, which could serve as a transmembrane anchor. Another interesting feature is the presence of seven consecutive glycine residues in the N-terminal region. This is even more remarkable since the protein is not rich in glycine. PMID- 2930776 TI - Quantification analysis of 5'-splice signal sequences in mRNA precursors. Mutations in rabbit beta-globin gene. AB - Concerning the signals which direct excision of introns from mRNA precursors in genes of higher eukaryotes, a consensus sequence composed of nine nucleotides, CAAG/GTAGAGT, has been proposed for the 5'-splice site, but actual 5'-splice site sequences differ from it to a greater or lesser degree. In the present paper, the 5'-splice site sequence of the rabbit beta-globin gene was analyzed using a quantification method (categorical discriminant analysis). In this method, each 9 nucleotide sequence in the pre-mRNA was characterized by its sample score, which shows the extent to which the sequence contains the signal. This approach could explain not only the location of the 5'-splice site, but also the experimental results of various point mutations in the 5'-splice region, as reported by Aebi et al. Our method further predicted the positions of cryptic 5'-splice sites, which are activated when the authentic 5'-splice site is abolished. PMID- 2930777 TI - Cloning and characterization of a histone gene family in Tilapia fish. AB - Genomic organization and expression of a histone gene family in the Tilapia (Cichlidae) fish was determined. A genomic library was prepared; four clones containing the complete set of core histones were analyzed. These clones differed significantly in their restriction maps, although three of them revealed a uniform internal gene arrangement of the core histone genes. Differential expression between two of the cloned clusters was observed when the hybridization pattern of those clusters to various RNA preparations was compared. The copy number of histone genes was estimated to be 100 to 110 for haploid Tilapia genome. PMID- 2930778 TI - An analysis by restriction enzymes of the genomic structure of the 3' untranslated region of the human estrogen receptor gene. AB - The estrogen receptor gene has a very long 3' untranslated region. As a first step towards the analysis of this structural feature for any functional role, we have cloned the human genomic estrogen receptor gene. Extensive restriction enzyme analysis of this DNA and comparison of the sizes of the DNA fragments obtained with those predicted from published cDNA sequences indicate that the 3' exon extends for at least 4304 bases from base number 2018 in the cDNA to the end of the cDNA. The data also show that the most 3' intron in this gene occurs between bases 1902 and 2018 of the cDNA. PMID- 2930779 TI - Reconstitution of nucleosomes in vitro with a plasmid carrying the long terminal repeat of Moloney murine leukemia virus. AB - The potential of nucleosome assembly along the sequence of a plasmid carrying the long terminal repeat (LTR) and its flanking region of Moloney murine leukemia virus was analyzed by in vitro reconstitution experiments with histones from chicken erythrocytes. The results of electrophoretic mobility-shift and micrococcal nuclease-digestion assays indicated that the plasmid DNA contained four preferred sites for nucleosome formation. However, all of these sites were mapped on the vector moiety but not on the LTR moiety. Computer analysis of the sequences in the four preferred sites, each spanning about 150 bp, indicated that short runs of (dA,dT) containing two kinds of triplets, AAA/TTT and AAT/ATT, occurred frequently. Furthermore, many of these triplets tended to occur in the same side of the DNA helix, suggesting that DNA curvature was involved in the preferred sites for nucleosome assembly. Consistent was the observation that DNA fragments carrying these preferred sites showed anomalous electrophoretic mobilities at a low temperature. PMID- 2930780 TI - Mutational analysis of the bacteriophage alpha 3 origin of complementary DNA synthesis: in vivo properties of mutants. AB - Bacteriophage alpha 3 origin of complementary strand DNA synthesis contains two potential secondary loop structures, I and II, which have been implicated in direct recognition sites for host Escherichia coli dnaG protein. To elucidate the function of the hairpin loops, we have introduced point mutations within the stem of the hairpin II so as to disturb its base-pairings. A mutant, oriAA, which had two point mutations in the region, formed minute plaques on E. coli host cells and its mean burst size at 37 degrees C was about 50, whereas that of wild-type was 250. In addition, the growth of oriAA at 42 degrees C was thermosensitive and the burst size was reduced to 5. From the oriAA, a revertant-like phage oriGA occurred spontaneously with a high-frequency of about 2.10(-2). It retained one point mutation and the plaque size and phage yield were nearly same as those of wild-type. These results are discussed with respect to the role of secondary structure as well as specific nucleotide sequence in the recognition site for the dnaG protein. PMID- 2930781 TI - Calcium translocation in liposome systems modeled on the mitochondrial inner membrane. AB - Ca2+ uptake by liposomes consisting of phosphatidylcholine (PC) and cardiolipin (CL) has recently been reported (Smaal, E.B. et al. (1987) Biochim. Biophys. Acta 897, 191-196). In eukaryotic cells, CL is localized exclusively in the inner mitochondrial membrane, where it occurs in the presence of equimolar amounts of PC and phosphatidyl-ethanolamine (PE). We have therefore re-examined CL-mediated Ca2+ translocation in liposomes of more nearly physiological composition, i.e., PC/PE/CL (2:2:1 and 4:4:1, mol/mol). In addition, the effect on Ca2+ uptake of plasmalogens of PE, which may account for up to 50% of mitochondrial PE, was determined. Our findings can be summarized as follows. (1) Ca2+ uptake into CL containing liposomes was increased dramatically by PE. (2) Ca2+ entry into PC/CL liposomes was biphasic; in the presence of PE, uptake was dominated by a slow process. (3) Ca2+ uptake by PC/CL liposomes saturated at less than or equal to 2 mM external Ca2+, whereas uptake into PC/PE/CL liposomes increased with increasing Ca2+ concentration up to 10 mM or until Ca2+ release ensued. (4) Ca2+ translocation by PE-containing liposomes and the slow phase of Ca2+ uptake into PC/CL liposomes were similarly and highly dependent on temperature. It can therefore be proposed that PE amplifies the slow component of CL-mediated Ca2+ translocation. This process is characterized by a requirement for high external Ca2+ concentrations and a large apparent activation energy. Ca2+ uptake was not significantly modified by plasmalogens of PE. PMID- 2930782 TI - Inhibition of red cell Ca2+-dependent K+ channels by snake venoms. AB - We have investigated the effects of several snake venoms on the Ca2+-dependent K+ channels of human red cells. A heat-resistant component of the venom of the snake Notechis scutatus irreversibly inhibited Ca2+-dependent K+ transport with a Ki value of 0.1-0.2 micrograms/ml. Metabolic changes of the cells modified the maximal effect of the venom. Binding of the venom required extracellular Ca2+ and was quick, but development of full inhibition required additional time. The effects of the venoms from Notechis scutatus and Leiurus quinquestriatus were additive, suggesting that both venoms act through different mechanisms. Venoms of the snakes Vipera russelli russelli and Oxyuranus scutellatus also inhibited Ca2+ dependent K+ transport with the same characteristics as the Notechis scutatus venom. PMID- 2930784 TI - The phase diagram of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/sucrose in the dry state. Sucrose substitution for water in lamellar mesophases. AB - The phase diagram of the binary system, 1,2-dipalmitoyl-sn-glycero-3 phosphocholine (DPPC)/sucrose, was determined by DSC. In contrast to dry DPPC, which exhibits chain melting at 342.5 K, the main feature of the DPPC/sucrose system is eutectic melting at 320 K. This was supported earlier by Crowe, J.H., Crowe, L.M. and Chapman, D. (Science 223 (1984) 701-703), who reported a drastic decrease in the chain-melting temperature of the dry lipid in the presence of some mono- and disaccharides. Electron microscopy suggests that the phase structures on either side of the phase transition are of the lamellar type. Definite sugar saturation concentrations can be derived from this phase diagram. Up to about 17 mol% sucrose, i.e., 1 mol of sucrose per 5 mol of lipid is adopted by DPPC in the low-temperature phase Lc. In the high-temperature phase Lm the saturation concentration is well above 90 mol% sucrose at 320 K (eutectic point) but decreases with increasing temperature. The lower limit of 50 mol% sucrose is reached at 455 K. At this temperature, peritectic melting of sucrose occurs. Because of some similarities in the phase diagrams of DPPC/sucrose and DPPC/water, it is possible to understand the sucrose substitution for water in dry lamellar mesophases. PMID- 2930783 TI - Bile acid binding proteins in hepatocellular membranes of newborn and adult rats. Identification of transport proteins with azidobenzamidotauro[14C]cholate ([14C]ABATC). AB - Neonatal hepatocytes are less active in uptake of bile acids than are mature hepatocytes. This phenomenon has been further investigated by transport studies with azidobenzamidotaurocholate (ABATC). Taurocholate, cholate and the photolabile ABATC were taken up by liver cells of adult rats by a sodium dependent and by an additional sodium-independent mechanism. In the dark, ABATC inhibited the uptake of taurocholate and cholate. Taurocholate decreased the transport of ABATC in a competitive manner, both in the presence and absence of sodium. In neonatal hepatocytes the Vmax for taurocholate and for ABATC was similar but was lower than in mature liver cells. In contrast, the Km was similar for neonatal and mature hepatocytes. For identification of binding proteins in both kinds of cells ABATC was photolysed after preincubation with isolated hepatocytes. Under our experimental conditions (single ultraviolet flash) about 80% of the azido groups was converted to nitrene. The covalently binding nitrene derivative inhibited bile salt transport irreversibly. Photolabeling of intact hepatocytes or of isolated plasma membranes with ABATC resulted in radioindication of membrane proteins with 67, 60, 54, 50 and 43 kDa in mature plasma membranes but of proteins with masses of 67, 54, 43 and 37 kDa in neonatal basolateral membranes. The 50 kDa protein in largely lacking in membranes of 9 day-old rats. The process of photolabeling itself was sodium-independent when isolated cells were treated with ABATC. In contrast, the degree of labeling of intact hepatocytes was markedly reduced in the absence of sodium and chloride. 100-fold molar excess of taurocholate, benzamidotaurocholate (BATC), phalloidin or cyclosomatostatin protected isolated plasma membranes against coupling of ABATC. Photolabeling of hepatoma cells known to be deficient in bile salt transport did not result in radiomodification of membrane proteins. PMID- 2930785 TI - Inhibition of enzymes and oxidative damage of red blood cells induced by t butylhydroperoxide-derived radicals. AB - The effects of t-butylhydroperoxide (tBHP), its alkoxyl radical (tBuO.) and its peroxyl radical (tBuOO.) in model systems and on red blood cells were studied. Glyceraldehyde-3-phosphate dehydrogenase was strongly inhibited by tBHP via a direct reaction of the hydroperoxide with an essential sulfhydryl group in the enzyme molecule. Several other enzymes were unaffected by tBHP. Alcohol dehydrogenase was strongly inhibited by tBuO. but was much less sensitive to tBuOO.. Lysozyme, lactate dehydrogenase and trypsin, on the other hand, were very sensitive to the peroxyl and not, or much less, to the alkoxyl radical, whereas acetylcholinesterase was very sensitive to both radicals. tBuOO. caused covalent binding of tryptophan, tyrosine, histidine and methionine to serum albumin. The corresponding alkoxyl radical was ineffective in this respect. Conversely, tBuO. caused peroxidation of linolenic acid, whereas tBuOO. did not. Incubation of human erythrocytes with tBHP caused lipid peroxidation and K+ leakage. Both effects were caused by tBHP-derived radicals generated in a reaction of the hydroperoxide with hemoglobin. With radical scavengers it was possible to dissociate tBHP-induced lipid peroxidation and K+ leakage, demonstrating that these two processes are not causally related. Experimental results indicate that tBuO. causes lipid peroxidation, whereas tBuOO. is responsible for K+ leakage. PMID- 2930786 TI - Stability and fusion of lipid vesicles containing headgroup-modified analogues of phosphatidylethanolamine. AB - We have used lipid mixing, contents mixing and contents-leakage assays to characterize the divalent cation-mediated interactions of vesicles composed of various headgroup-modified analogues of phosphatidylethanolamine, PE (N- and C-2 alkylated derivatives, and analogues with increased separations of the phosphoryl and amino groups) together with a low mole percentage of phosphatidylserine (PS). Vesicles containing different structural analogues of PE exhibit marked differences, both in the threshold divalent cation concentrations that are required to initiate vesicle-vesicle interactions and in the rates of contents mixing and leakage observed at suprathresholds divalent cation concentrations. The efficiencies of divalent cation-promoted contents leakage, and to a slightly lesser extent those of contents mixing, for PS/PE (analogue) vesicles show a marked inverse correlation with the lamellar-to-hexagonal II transition temperature (TH) of the PE (analogue) component. However, the destabilization kinetics for such vesicles show no abrupt changes over the temperature range around the equilibrium TH value measured for the vesicle lipids. Vesicles combining PS with different PE analogues exhibit divalent cation thresholds for aggregation that are not correlated with the TH values of the PE (analogue) components but appear instead to be correlated with the equilibrium interbilayer separations measured in multilamellar dispersions of these species. We have identified headgroup-modified analogues of PE that can be used to prepare vesicles that fuse more rapidly under a given set of conditions, or that show a bette ratio of fusion-to-contents-leakage rates, than do PE-containing vesicles. These results may be useful both for understanding better the bases for the high fusion-supporting ability of PE and for the preparation of lipid vesicles 'tailored' for particular practical applications. PMID- 2930787 TI - Relationship of hyperthermia-induced hemolysis of human erythrocytes to the thermal denaturation of membrane proteins. AB - Hemolysis of human erythrocytes as a function of time of exposure to 47.4-54.5 degrees C was measured and correlated to thermal transitions in the membranes of intact erythrocytes as determined by differential scanning calorimetry (DSC). Curves of hemoglobin leakage (a measure of hemolysis) as a function of time have a shoulder region exhibiting no leakage, indicative of the ability to accumulate sublethal damage (i.e., damage not sufficient to cause lysis), followed by a region of leakage approximating pseudo-first-order kinetics. Inverse leakage rates (Do) of 330-21 min were obtained from 47.4-54.5 degrees C, respectively. A relatively high activation energy of 304 +/- 22 kJ/mol was obtained for leakage, eliminating the involvement of metabolic processes but implicating a transition as the rate-limiting step. Membrane protein involvement was suggested by the very low rate (10(-2) of the rate from erythrocytes) and low activation energy (50 +/- 49 kJ/mol) of hemoglobin leakage from liposomes containing no membrane protein. A model was developed that predicts a transition temperature (Tm) for the critical target (rate-limiting step) of 60 degrees C when measured at a scan rate of 1 K/min. DSC scans were obtained from intact erythrocytes and a procedure developed to fit and remove the transition for hemoglobin denaturation which dominated the scan. Three transitions remained (transitions A, B, and C) with Tm values of 50.0, 56.8, and 63.8 degrees C, respectively. These correspond to, but occur at slightly different temperatures than, the A, B, and C transitions of isolated erythrocyte membranes in the same salt solution (Tm = 49.5, 53-58, and 65.5 degrees C, respectively). In addition, the relative enthalpies of the three transitions differ between isolated membranes and erythrocytes, suggestive of membrane alterations occurring during isolation. Thus, all analyses were conducted on DSC scans of intact erythrocytes. The B transition is very broad and probably consists of several transitions. An inflection, which is seen as a distinct peak (transition B3) in fourth-derivative curves, occurs at 60.8 degrees C and correlates well with the predicted Tm of the critical target. Ethanol (2.2%) lowers the Tm of B3 by 4.0-4.5 K, close to the shift of 3.3 K predicted from its effect on hemolysis. Glycerol (10%) has very little effect on both hemolysis and the Tm of B3, but it stabilizes spectrin (delta Tm = 1.5 K) against thermal denaturation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2930788 TI - Synthesis and characterization of fluorescent Lucifer yellow-lipid conjugates. AB - The syntheses of fluorescent lipid probes composed of Lucifer yellow dyes linked to either cholesterol or phospholipids are described. The spectral properties of these probes are characterized, and the probes are evaluated for use with model membranes and with live animal and plant cells. Of the probes synthesized, the cholesterol derivative is the easiest to prepare and appears to be the most useful because it readily labels the plasma membrane of live cells and maintains a high ratio of cell surface-to-cytoplasmic fluorescence. PMID- 2930789 TI - Water permeability in the human amnion: pH regulation of the paracellular pathway. AB - Human amnion was mounted, immediately after delivery, as a diaphragm between two lucite chambers and the net transepithelial water movement (Jw) was recorded minute by minute. When Jw was plotted against the applied transepithelial hydrostatic pressure (fetal side positive), in the absence of any other gradient, a linear relationship was observed (Phydr = 0.32 +/- 0.05 cm/s, n = 10). A linear relationship was also found when Jw was measured in the presence of an osmotic gradient, generated by adding (to the maternal side) different concentrations of poly(ethylene glycol) (Mr approximately equal to 3600; reflexion coefficient (sigma) = 1; Posm = 0.015 +/- 0.001 cm/s, n = 10). When sucrose, a paracellular marker, was used as the osmotic probe, the observed sigma was 0.5. Medium acidification in the presence of bicarbonate reduced in the same proportion both the hydrostatic and osmotic permeabilities. The effect was fully reversible, but was not observed when bicarbonate was replaced by Tris. To test the comparative role of transcellular versus paracellular paths, Jw and the [14C]sucrose permeability (Psuc) were simultaneously recorded minute by minute, in the presence of an osmotic or an hydrostatic gradient. In both cases, the percentage reductions in Jw and Psuc induced by medium acidification were similar. Quantification of theoretical and observed values for Jw and Psuc strongly suggests that effects of pH on both the osmotic and hydrostatic flux reflect a modification of the paracellular path. PMID- 2930790 TI - Effect of cholesterol on the uptake and intracellular degradation of liposomes by liver and spleen; a combined biochemical and gamma-ray perturbed angular correlation study. AB - We investigated the effect of cholesterol on the uptake and intracellular degradation of liposomes by rat liver and spleen macrophages. Multilamellar vesicles (MLV) consisting of distearoylphosphatidylcholine/phosphatidylserine (molar ratio 9:1) or distearoylphosphatidylcholine/cholesterol/phosphatidylserine (molar ratio 4:5:1) were labeled with [3H]cholesteryl hexadecyl ether and/or cholesteryl [14C]oleate. After i.v. injection the cholesterol-containing liposomes were eliminated less rapidly from the bloodstream and taken up to a lesser extent by the liver (macrophages) than the cholesterol-free liposomes. Assessment of the 3H/14C ratios in liver and spleen cells revealed that the cholesterol-containing liposomes are substantially more resistant towards intracellular degradation than the cholesterol-free liposomes. These results could be confirmed by measuring the release of 111In from liposomes after uptake by liver and spleen by means of gamma-ray perturbed angular correlation spectroscopy. Experiments with cultured Kupffer cells in monolayer also revealed that incorporation of cholesterol results in a decrease of the uptake and an increase of the intracellular stability of cholesteryl [14C]oleate-labeled liposomes. Finally, incubation of both types of liposomes with lysosomal fractions prepared from rat liver demonstrated a difference in susceptibility to lysosomal degradation: the cholesterol-free vesicles were much more sensitive to lysosomal esterase than the cholesterol-containing liposomes. These results may be relevant to the application of liposomes as a drug carrier system to liver and spleen (macrophages). PMID- 2930791 TI - Dicarboxylate transport in human placental brush-border membrane vesicles. AB - Pathways for transport of dicarboxylic acid metabolites by human placental epithelia were investigated using apical membrane vesicles isolated by divalent cation precipitation. The presence of Na+/dicarboxylate cotransport was assessed directly by [14C]succinate tracer flux measurements and indirectly by fluorescence determinations of voltage sensitive dye responses. The imposition of an inwardly directed Na+ gradient stimulated vesicle uptake of succinate achieving levels approximately 5-fold greater than those observed at equilibrium. The increased succinate uptake was specific for Na+ as no stimulation was observed in the presence of Li+, K+ or choline+ gradients. In addition to concentrative accumulation of succinate, a direct coupling of Na+/succinate cotransport was suggested by the absence of a sizeable conductive pathway for succinate uptake and decreased succinate uptake levels associated with a more rapid decay of an imposed Na+ gradient. Na+ gradient-driven succinate uptake was not the result of parallel Na+/H+ and succinate/OH- exchange activities but was reduced by the Na+-coupled inhibitor harmaline. The voltage sensitivity of Na+ gradient-driven succinate uptake suggests Na+/succinate cotransport is electrogenic occurring with net transfer of positive charge. Substrate specificity studies suggest the tricarboxylic acid cycle intermediates as candidates for transport by the Na+-coupled pathway. Decreasing pH increased the citrate-induced inhibition of succinate uptake suggesting divalent citrate as the preferred substrate for transport. Initial rate determinations of succinate uptake indicate succinate interacts with a single saturable site (Km 33 microM) with a maximal transport rate of 0.5 nmol/mg per min. PMID- 2930792 TI - Preparation and polymerization properties of monomeric ADP-actin. AB - An improved method for the preparation of Mg-ADP-actin and Ca-ADP-actin which minimizes denaturation of the protein has been developed. Using ADP-actin prepared by this method, we have measured the polymerization characteristics of Mg-ADP-actin and Ca-ADP-actin. In contrast to the significant difference in Mg ATP-actin and Ca-ATP-actin polymerization characteristics that we reported previously (J. Muscle Res. Cell Motility 7 (1986) 215-224), we show here that values for the critical concentration, the relative rate constant of elongation (mk+) and the relative rate constant of depolymerization (mk-) for Mg-ADP-actin are similar to those for Ca-ADP-actin. The value of mk+ for Mg-ATP-actin is about 8-fold higher than that for Mg-ADP-actin and the value of mk- for Mg-ADP-actin is 3-4-fold higher than that for Mg-ATP-actin. These factors may help explain the observation that the spontaneous nucleation rates of both types of ADP-actin are low in contrast to the rapid nucleation of Mg-ATP-actin. PMID- 2930793 TI - Modelling of chemical reactions catalysed by membrane-bound enzymes. Determination and significance of the kinetic constants. AB - A model of multiphasic systems, based on the assumption of zero-order partition of substrates and products into the membranes, is applied to reversible mono substrate and bi-substrate reactions catalysed by membrane-bound enzymes. Apart from replacement of single-phase kinetic constants by apparent kinetic constants, the derived kinetic expressions are formally identical with those for corresponding single-phase systems. The model confers to the apparent kinetic constants an experimentally verifiable meaning. For full characterization of membrane-kinetic systems, experiments at various concentrations of enzyme embedding phospholipid are required. Extrapolation to zero phospholipid concentration of each Km app then yields the corresponding true kinetic constant characteristic of the membrane-bound enzyme and also provides a technique for determination of the membrane-partition constants. The procedure implies that the phospholipid content should be assayed for full characterization of membrane bound enzymes. If, for practical reasons, the assays have to be limited to a single enzyme concentration, correction of the apparent kinetic constants is still possible provided the phospholipid concentration and the partition constants of the reactants are known. The model has permitted prediction of a number of previous observations reflecting the multiphasic nature of the systems. The assumptions, underlying the model, and their implications are examined as well as some commonly used experimental designs for determination of the type of enzymic site. PMID- 2930794 TI - Purification and properties of mouse stomach aldehyde dehydrogenase. Evidence for a role in the oxidation of peroxidic and aromatic aldehydes. AB - The major isozyme of aldehyde dehydrogenase in mouse stomach, AHD-4, has been purified to homogeneity and characterized with a range of aldehyde substrates at pH 7.4. The enzyme was a dimer with a subunit size of 65 kDa. Using V/Km values as an indication of substrate efficacy, aromatic aldehydes were the preferred substrates. The enzyme used either NAD+ or NADP+ as cofactor, but showed a preference for NAD+. AHD-4 showed 'high-Km' properties with respect to acetaldehyde, but differed from the 'high-Km' liver mitochondrial enzyme (AHD-1), in that it was not a semialdehyde dehydrogenase. The enzyme was significantly active towards the peroxidic aldehyde, 4-hydroxynonenal, and may play a role in vivo in the detoxification of aromatic aldehydes and the aldehyde products of lipid peroxidation. PMID- 2930795 TI - Role of a partially purified glutathione S-transferase from rat liver nuclei in the inhibition of nuclear lipid peroxidation. AB - Glutathione protects isolated rat liver nuclei against lipid peroxidation by inducing a lag period prior to the onset of peroxidation. This GSH-dependent protection was abolished by exposing isolated nuclei to the glutathione S transferase inhibitor S-octylglutathione. In incubations containing 0.2 mM S octylglutathione, the GSH-induced lag period was reduced from 30 to 5 min. S Octylglutathione (0.2 mM) also completely inhibited nuclear glutathione S transferase activity and reduced glutathione peroxidase activity by 85%. About 70% of the glutathione S-transferase activity associated with isolated nuclei was solubilized with 0.3% Triton X-100. This solubilized glutathione S-transferase activity was partially purified by utilizing a S-hexylglutathione affinity column. The partially purified nuclear glutathione S-transferase exhibited glutathione peroxidase activity towards lipid hydroperoxides in solution. The data from the present study indicate that a glutathione S-transferase associated with the nucleus may contribute to glutathione-dependent protection of isolated nuclei against lipid peroxidation. Evidence was obtained which indicates that this enzyme is distinct from the microsomal glutathione S-transferase. PMID- 2930796 TI - The high molecular weight multicatalytic proteinase, macropain, exists in a latent form in human erythrocytes. AB - The high molecular weight multicatalytic proteinase, macropain, has been purified from human erythrocytes in two forms that differ in caseinolytic activity up to 100-fold. Each form has a native molecular weight of 600,000 and is composed of a number of subunits ranging in molecular weights from 35,000 to 21,000. Although the two proteinase forms share a number of electrophoretically indistinguishable subunits, there are also subunits unique to the respective forms. The less active proteinase represents a latent enzyme because it was fully activated by two procedures including dialysis against water and pretreatment with low concentrations of sodium dodecyl sulfate. These procedures caused differential changes in the caseinolytic and two peptidase activities of the proteinase. An Mr 35,000 subunit, characteristic of latent macropain, is immunologically related to at least one of the other components of active macropain and disappeared after proteinase activation by dialysis. Nevertheless, loss of this subunit was not the cause of the increased activity. These results suggest that the proteolytic activity of cells may be regulated by the activation of the latent form of macropain. PMID- 2930797 TI - Distribution and solubilization of the molecular forms of acetylcholinesterase in rat urinary bladder and sphincter. AB - The distribution and solubility of the molecular forms of acetylcholinesterase (acetylcholine acetylhydrolase, EC 3.1.1.7) were examined in adult, male rat bladder body and sphincter. Four distinct forms of the enzyme solubilized from bladder body were separated on sucrose density gradients. Two of the forms (A8 and A12) corresponded to asymmetric proteins and were solubilized with high ionic strength buffer. The other two forms represented globular forms. The smallest form (G1) was soluble in low ionic strength buffer without detergent. About 33% of the larger globular form (G4) required detergent for solubilization. There were only minor differences in the distribution of these forms in juvenile rat bladder and adult, female rat bladders. Sphincter tissue lacked one of the asymmetric forms but otherwise resembled the bladder bodies. These results demonstrate that some smooth muscle organs have significant amounts of asymmetric, as well as globular, forms of acetylcholinesterase and suggest that additional studies should be performed to characterize the enzyme in this and other smooth muscle systems. PMID- 2930798 TI - Identification of the rate-limiting step in serine proteinases from the effect of temperature on steady-state kinetics. AB - The effect of temperature on the steady-state kinetics of porcine pancreatic elastase can be used to determine whether acylation or deacylation is the rate limiting step in catalysis. If acylation is rate-limiting, kcat and kcat/Km will show the same temperature dependence. If deacylation is rate-limiting, kcat will show a greater temperature dependence than kcat/Km. The temperature dependence of the steady-state kinetic parameters of t-Boc-Ala-Ala-Pro-Ala p-nitroanilide and N acetyl-Ala-Ala-alpha-Aza-Ala p-nitrophenyl ester have been determined and are consistent with this prediction. PMID- 2930799 TI - Idiot's triumph: as told by an idiot. PMID- 2930800 TI - Assessing improvements in the dexamethasone suppression test using receiver operating characteristics analysis. AB - This article demonstrates methods by which receiver operating characteristics (ROC) analysis may be used to evaluate and improve the Dexamethasone Suppression Test (DST). ROC indices provide a description of nonbinary diagnostic tests that is independent of any particular cutoff and that allows investigators to use rigorous mathematical methods for selecting cutoffs and assessing overall performance. In this study, ROC analyses of previously published data suggest that (1) the accuracy of the DST might be improved by using a 0.5-mg oral steroid dose; (2) incorporation of dexamethasone serum levels does not improve the performance of the DST; and (3) the serum cortisol level used to define "no suppression" (or DST "positivity") should be varied to take into account diagnostic alternatives, prior probability of affective disorder, and the clinical goal for performing the test (e.g., maximizing utility, increasing information). PMID- 2930801 TI - Frontal cerebral lesions and violent incidents in chronic neuropsychiatric patients. AB - The contribution of selected neurological, psychiatric, and demographic variables to the frequency of violent incidents was studied in an institutional context. A multiple regression procedure was used to predict the number of documented incidents for each of 45 neuropsychiatric patients. This procedure yielded a 5 variable equation that accounted for close to a third of the variance. The first three variables entered each contributed uniquely to validity. These variables were presence of focal frontal cerebral lesions, number of inpatient days, and history of seizure disorder. The presence of cerebral damage in general did not predict violent incidents. The results are discussed in terms of possible brain behavior relationships and the nature of the patient population. PMID- 2930802 TI - Sensation seeking and auditory evoked potentials. AB - The relationship between auditory evoked potentials (AEP) and the German version of Zuckerman's Sensation Seeking Scale was examined. The slope of the amplitude/stimulus intensity function (N1/P2 component) and the N1 latency were particularly studied, as these variables have been found to be potential predictors of the response to lithium prophylaxis. Thirty-three healthy subjects participated in two testing series on the first day and in a third run 3 weeks later. Binaural clicks at four intensity levels (58, 68, 78, 88 dB HL, ISI 2.1 sec) were presented in randomized order by headphone. Eighty responses were averaged at each intensity level. The pattern of correlation between the German version of the Sensation Seeking Scale and a personality inventory (FPI) supports the validity of the Sensation Seeking Scale. Only a tendency toward steeper slopes of the amplitude/stimulus intensity function (ASF) in high sensation seekers was observed in the first run. However, there was a significant interaction of sensation seeking and the test run. Only high sensation seekers showed an influence of retesting on the slope of the ASF, leading to a decrease of the slope in the second, compared with the first run. This might correspond to the psychological pattern of sensation seeking, which is characterized by a permanent need for new and exciting situations and, at the same time, by a rapid loss of interest in these situations. With regard to the N1 latency, a significant interaction of sensation seeking and lead was found. Low sensation seekers showed longer N1 latencies over the right than over the left hemisphere, a finding that accords with some psychophysiological theories on the relation between asymmetric hemispherical activation and certain psychological constructs. Our results support the view that sensation seeking is a personality feature that is closely related to certain physiological variables. PMID- 2930803 TI - Hand preference in psychotic twins. AB - In an attempt to replicate the influential study of Boklage (1977), hand preference for writing was examined in a new series of 30 monozygotic (MZ) and 30 dizygotic (DZ) twin pairs in whom the proband had suffered a functional psychosis. In contrast to the original report, no increased rate of left handedness was found in MZ compared to DZ twins, or psychotic compared with nonpsychotic twins. In particular, no relationship between within-pair left handedness and discordance for psychosis emerged. Possible reasons for the disagreement between the two studies are examined. PMID- 2930804 TI - Cognitive impairment and cortisol resistance to dexamethasone suppression in elderly depression. AB - The present study evaluates the relationship between cognitive impairment and the Dexamethasone Suppression Test (DST) in elderly persons suffering from depression. Twenty-nine subjects meeting DSM-III criteria for major depressive disorder (MDD) were assessed using the Global Deterioration Scale (GDS) and the DST. Plasma cortisol levels before and after receiving 0.5 mg dexamethasone were compared, and correlations were determined between GDS and postdexamethasone plasma cortisol levels. The results show that there is a positive correlation between the GDS scores and post-DEX cortisol levels (r = 0.57, p less than 0.005). It is suggested that increased activity of the HPA axis, seen in depression, could contribute to the cognitive impairments observed in this disorder. PMID- 2930805 TI - Sensitivity to N-methyl-N'-nitro-N-nitrosoguanidine in fibroblasts from patients with schizophrenia. PMID- 2930806 TI - Everything is addictive. PMID- 2930807 TI - Does platelet serotonin receptor supersensitivity accompany endogenous depression? AB - In a population of drug-free bipolar and unipolar depressed women, it was found that the concentration of serotonin sufficient to induce half-maximal shape change velocity in platelets is significantly (p less than 0.001) lower (0.13 +/- 0.0.04 microM) than that of closely matched controls (0.532 +/- 0.1 microM). This platelet concentration becomes higher after 1-3 months of antidepressant treatment (0.47 +/- 0.16 microM). Possible mechanisms for this up- or down regulation of platelet serotonin receptor responsiveness are discussed. PMID- 2930808 TI - Aberrant seasonal variations of platelet serotonin uptake in endogenous depression. AB - The serotonin uptake in platelets of 120 healthy volunteers and 64 endogenously depressed patients was investigated over a 2-year period. In healthy individuals, Km exhibited a significant seasonal rhythm during the bright half of the year. The seasonal rhythm of Vmax assumes the form of a sine curve, with nadir values at the vernal and autumn equinoxes and peak values at the winter and summer solstices. Km in patients was higher than in controls in February and October, and the seasonal variation of Km differed between patients and controls. The monthly mean values of Vmax in patients were, as a rule, lower than corresponding values in controls, but significantly so only in December. Patients had higher Vmax than controls in October and November, and the seasonal variation of Vmax in patients differed from that of controls. The results suggest that Km, a measure of the affinity of the serotonin uptake site, may be subject to photoperiodic regulation in healthy individuals. The annual variation in uptake site densities, as judged by the changes in Vmax, are probably generated by an endogenous superior oscillator. The aberrant uptake kinetics found in the endogenously depressed patients may reflect seasonal susceptibility to the disorder and/or altered serotonergic rhythmicity. PMID- 2930809 TI - Differential effects of scopolamine on nocturnal cortisol secretion, sleep architecture, and REM latency in normal volunteers: relation to sleep and cortisol abnormalities in depression. AB - Scopolamine (SCOP) (3.0 mu/kg and 6.0 micrograms/kg) and saline were administered intramuscularly at 11:00 PM to eight normal male volunteers in a randomized design, and the effects on the sleep electroencephalogram (EEG) and nocturnal cortisol secretion (via blood sampling every 15 min) were evaluated. Compared to saline, SCOP produced a significant dose-related delay in rapid eye movement (REM) latency. In contrast, neither dose of SCOP significantly affected nocturnal plasma cortisol concentrations. These results suggest that the central cholinergic system that regulates the onset of REM sleep is more sensitive to dysregulation than the cholinergic system that controls the degree of nocturnal cortisol secretion. If central cholinergic overactivity is responsible for both the REM sleep latency and cortisol abnormalities in depressed patients, then our findings with SCOP might help explain why the incidences of these abnormalities are different. PMID- 2930810 TI - Toxic ictal delirium. AB - Delirium, also known as acute confusional state, is a common reversible organic psychiatric syndrome. This paper focuses on toxic delirium associated with prominent paroxysmal electroencephalogram (EEG) dysfunction occurring in nonepileptic patients. Our data derive from observations in two conditions, viz., delirium induced by hypnosedative drug withdrawal and confusion activated by psychotropic drug overdosage. It is suggested that in these conditions, delirium represents a generalized symptomatic nonconvulsive epileptic state following a transient transmitter dysfunction. Dramatic relief of both clinical and EEG dysfunction by intravenous benzodiazepines is reported in detail. Finally, the informative value of the EEG in the differential diagnosis of acute confusional states is emphasized. PMID- 2930811 TI - Psychopathological alterations in cases of symmetrical basal ganglia sclerosis. AB - Psychopathological alterations caused by symmetrical basal ganglia sclerosis of different etiologies are described, involving cases with parathyroid gland/hormone dysfunction (some of them familial), patients after thyroidectomy, and patients with basal ganglia calcification of uncertain etiology. Initial symptomatology in a group of 62 patients is reported; chronic symptoms in another group of 35 patients were evaluated. Estimates of volume of the basal ganglia calcifications were made, in addition to precise topographical localizations by CT. In 40% the initial symptoms noted were psychiatric, compared with 50% who first presented neurological symptoms. In the group of chronic cases practically all showed intellectual impairment. There was a marked preponderance of organic affective syndromes (initially 21%, chronic 65%): the affective chronic patients can be subdivided into 37% depressive, 20% bipolar, 11% manic cases. We could find no direct relationships with regard to etiology, localization, volume or symptoms, except that extensive calcifications occur after parathyroid hormone deficiencies due to thyroidectomy and lead to more severe mental deterioration. PMID- 2930812 TI - Differential reactivity to lactate infusions: the relative role of biological, psychological, and conditioning variables. AB - Nine patients with panic disorder experienced a lactate-induced panic attack, whereas nine controls did not. Higher preinfusion anxiety levels and heart rates were associated with panic disorder, and high baseline anxiety ratings were associated with atypical, severe lactate-induced panic attacks. Nevertheless, it was difficult to reconcile patients' and controls' reactivity to lactate as entirely secondary to baseline differences. Subjects differed qualitatively in the types of specific symptoms experienced and quantitatively in their anxiety and heart rate responses. In most cases, panic began with various central perceptual changes; peripheral cardiovascular and autonomic symptoms followed later. No patient rated a lactate-induced panic attack as identical to a naturally occurring attack. Not only did specific symptoms differ in their severity and order of production, but lactate-induced panic lacked the typical fears of dying, going crazy, or losing control. The results suggest that though environmental effects, expectancy biases, and baseline psychological states play salient roles in modifying the experience of a lactate-induced panic attack, they do not fully account for lactate sensitivity. The relative role that biological, psychological, and conditioning factors play in lactate-induced panic is discussed. PMID- 2930813 TI - Middle latency evoked potentials in melancholic depression. PMID- 2930814 TI - Nocturnal plasma melatonin levels in schizophrenic patients. PMID- 2930815 TI - HLA system and panic attacks. PMID- 2930816 TI - State-related changes in norepinephrine regulation in anorexia nervosa. PMID- 2930818 TI - Regional stress in a noncircular cylinder. AB - Several mathematical formulas are presented for estimating regional average circumferential stress and shear stress in a thick-wall, noncircular cylinder with a plane of symmetry. The formulas require images of exterior and interior chamber silhouettes plus surface pressures. The formulas are primarily intended for application to the left ventricle in the short axis plane near the base (where the meridional radius of curvature is normally much larger than the circumferential radius of curvature) and to blood vessels. The formulas predict stresses in a variety of chambers to within 3% of finite element values determined from a large-scale structural analysis computer program called ANSYS. PMID- 2930817 TI - Frequency specificity in intercellular communication. Influence of patterns of periodic signaling on target cell responsiveness. AB - Cells often communicate by means of periodic signals, as exemplified by a large number of hormones and by the aggregation of Dictyostelium discoideum amebas in response to periodic pulses of cyclic AMP. Periodic signaling allows bypassing the phenomenon of desensitization brought about by constant stimuli. To gain further insight into the efficiency of pulsatile signaling, we analyze the effect of periodic stimulation on the dynamic behavior of a receptor system capable of desensitization toward its ligand. We first show that the receptor system adapts to square-wave stimuli, i.e., the response eventually reaches a steady, periodic pattern after a transient phase. By analyzing the dependence of the response on the characteristics of the square-wave stimulation, we show that there exist a waveform and a period of that signal that result in maximum responsiveness of the target system. Similar results are obtained when the signal takes the more realistic form of a periodically repeated stimulation followed by exponential decay of the ligand. The results are discussed with respect to the role of pulsatile secretion of gonadotropin-releasing hormone (GnRH) by the hypothalamus and of periodic signaling by cyclic AMP pulses in Dictyostelium. The analysis accounts for the existence, in both cases, of an optimal frequency and waveform of the periodic stimulus that correspond to maximum target cell responsiveness. PMID- 2930819 TI - Synchronization between beating cilia. AB - A novel quantitative parameter is proposed to define and measure the degree of synchronization between two small ciliary areas. These areas can be close to or far from one another. The Pearson correlation factor is used to define the degree of synchronization by a single number. This approach is based on a computerized, dual photoelectric method which simulataneously measures the scattered light from two small areas on the ciliary epithelium or its tissue culture. The measurements were performed on tissue culture from frog's palate epithelium. It was found that: (a) the degree of synchronization decreases, as a function of distance; (b) the correlation is fairly high even at relatively large separations, when measured on the same patch; (c) on a given patch the synchronization factor is independent of the direction of the metachronal wave; (d) close disconnected ciliary cells exhibit fairly high correlation; (e) disconnected randomly choosen ciliary cells at relatively large separation distances exhibit relatively low correlation, smaller by a factor of 2 than the correlation factor at the same distances when measured along the metachronal wave; (f) the average frequencies' ratio and the metachronal wavelength can be used as first-order indicators of ciliary synchronization; (g) there is a spread of metachronal wavelengths even over a single well-organized patch. PMID- 2930820 TI - Halorhodopsin and sensory rhodopsin contain a C6-C7 s-trans retinal chromophore. AB - Halorhodopsin (HR) and sensory rhodopsin (SR) have been regenerated with retinal analogues that are covalently locked in the 6-s-cis or 6-s-trans conformations. Both pigments regenerate more completely with the locked 6-s-trans retinal and produce analogue pigments with absorption maxima (577 nm for HR and 592 nm for SR) nearly identical to those of the native pigments (577 and 587 nm). This indicates that HR and SR bind retinal in the 6-s-trans conformation. The opsin shift for the locked 6-s-trans analogue in HR is 1,200 cm-1 less than that for the native chromophore (5,400 cm-1). The opsin shift for the 6-s-trans analogue in SR is 1,100 cm-1 less than that for the native retinal (5,700 cm-1). This demonstrates that approximately 20% of the opsin shift in these pigments arises from a protein-induced change in the chromophore conformation from twisted 6-s cis in solution to planar 6-s-trans in the protein. The reduced opsin shift observed for the locked 6-s-cis analogue pigments compared with the locked 6-s trans pigments may be due to a positive electrostatic perturbation near C7. PMID- 2930821 TI - Internal and external K+ help gate the inward rectifier. AB - Recent investigations have demonstrated substantial reductions in internal [K+] in cardiac Purkinje fibers during myocardial ischemia (Dresdner, K.P., R.P. Kline, and A.L. Wit. 1987, Circ. Res. 60: 122-132). We investigated the possible role these changes in internal K+ might play in abnormal electrical activity by studying the effects of both internal and external [K+] on the gating of the inward rectifier iK1 in isolated Purkinje myocytes with the whole-cell patch clamp technique. Increasing external [K+] had similar effects on the inward rectifier in the Purkinje myocyte as it does in other preparations: increasing peak conductance and shifting the activation curve in parallel with the potassium reversal potential. A reduction in pipette [K+] from 145 to 25 mM, however, had several dramatic previously unreported effects. It decreased the rate of activation of iK1 at a given voltage by several-fold, reversed the voltage dependence of recovery from deactivation, so that the deactivation rate decreased with depolarization, and caused a positive shift in the midpoint of the activation curve of iK1 that was severalfold smaller than the associated shift of reversal potential. These changes suggest an important role of internal K+ in gating iK1 and may contribute to changes in the electrical properties of the myocardium that occur during ischemia. PMID- 2930822 TI - The spectrin network as a barrier to lateral diffusion in erythrocytes. A percolation analysis. AB - The spectrin network on the cytoplasmic surface of an erythrocyte can be modeled as a triangular lattice of spectrin tetramers (Tsuji, A., and S. Ohnishi, 1986. Biochemistry. 25:6133-6139). The tetramers act as barriers to protein diffusion, while dissociated dimer pairs, single dimers, and missing tetramers do not. Diffusion in the presence of these barriers is shown to be equivalent to bond percolation on the honeycomb lattice. Monte Carlo calculations for this system then yield the relative diffusion constant of a mobile integral protein as a function of the fraction of spectrin tetramers. At high concentrations of spectrin tetramer, long-range diffusion is blocked, but short-range diffusion is still possible. Monte Carlo calculations yield the average distance over which short-range diffusion can occur, as a function of the fraction of spectrin tetramers. Applications to erythrocyte development and hereditary hemolytic anemia are discussed. PMID- 2930823 TI - Potassium channel of cardiac sarcoplasmic reticulum is a multi-ion channel. AB - We have characterized mechanisms of ionic permeation in the K channel of canine cardiac sarcoplasmic reticulum (SR K channel). Ionic selectivity, as measured by relative permeabilities, followed Eisenman sequence l, a low field strength sequence. Slope conductance measured in symmetrical solutions across the bilayer followed Eisenman sequence V. In all cases, the selectivity characteristics of the prominent subconductance state (O1) were similar to those of the main-state (O2). Further, our studies have revealed that this channel differs in three significant ways from the highly characterized SR K channel of skeletal muscle. First, the ratio of permeabilities Cs+ to K+ was a complex function of ion concentration. Second, the concentration dependence of conductance was not well described by the Michaelis-Menten formalism. Instead, we modeled the observed relations using a more general approach based on classical rate theory. Third, mole fraction experiments (Cs+ with K+) demonstrated a prominent anomalous effect. Certain of our Cs+ data required the Eyring rate theory approach for adequate interpretation. We adopted a symmetrical energy profile incorporating ion-ion interaction and thereby accounted for much of the data. We conclude that the canine cardiac SR K channel is significantly different from that of skeletal muscle, and it may accommodate more than one ion at a time. PMID- 2930824 TI - A lyotrope gradient method for liquid crystal temperature-composition-mesomorph diagram construction using time-resolved x-ray diffraction. AB - A new method for rapidly constructing isobaric temperature-composition-mesomorph (T-C) diagrams is described. The method involves establishing a lyotrope concentration gradient in a liquid crystal lengthwise in an x-ray capillary tube. At a fixed temperature such a sample corresponds to an isotherm in the corresponding isobaric T-C diagram. The concentration gradient is conveniently established by bringing the two components into contact in the capillary and allowing limited diffusion of one component into the other. Phase boundaries are located and phases are identified and structurally characterized continuously along the length of the capillary using time-resolved x-ray diffraction. Repeating the measurement on the same sample at a series of temperatures in the range of interest completes that T-C diagram. The method has been used to construct the T-C diagram for detergent/water and lipid/water binary and ternary systems in the 20-120 degrees C range. They agree well with and extend the results obtained by conventional methods. PMID- 2930825 TI - Intracellular pH and cell-to-cell transmission in sheep Purkinje fibers. AB - Intracellular pH (pHi) is a significant modifier of cell-to-cell communication in some tissues but its role is uncertain in heart tissue. The present studies examined the effect of cytosolic protons on electrotonic spread and conduction velocity in cardiac Purkinje fibers. Cable analysis provided values for internal longitudinal resistance (ri) and pH-selective microelectrodes monitored pHi during CO2 and HCO3- alterations. Resting fibers developed changes in ri that were proportional to intracellular free proton concentration ([H+]i) during CO2 changes at constant [HCO3-]. However, the effects on ri were small between pHi 6.9-7.8 and predicted only a 2.2% increase in ri per 10 nM increase in [H+]i. Other findings suggested that titration of cytosolic protons may not directly produce the changes in ri: (a) For an equal change in [H+]i, the effects on ri were roughly three times greater (6.8% increase per 10 nM rise in [H+]i) if bicarbonate was lost during CO2 changes. (b) pH-associated changes in ri were preceded by a time delay (1-5 min) producing hysteresis in the [H+]i-ri relation during successive perturbations. (c) The same CO2 variations modified the direction and magnitude of ri differently during pacing than at rest. The cumulative results suggest that the action of protons on ri in the heart may be subordinate to another regulator or mediated by another pH-dependent substance or reaction. PMID- 2930826 TI - Adenosine triphosphate utilization rates and metabolic pool sizes in intact cells measured by transfer of 18O from water. AB - The hydrolytic rates and metabolic pool sizes of ATP were determined in intact cells by monitoring the time courses of 18O incorporation from 18O-water into the gamma-phosphoryl of ATP and orthophosphate. To calculate the rate of ATP hydrolysis, a kinetic model is used to fit the time course of the 18O labeling. The size of the metabolic pool of ATP is calculated from the 18O distribution after isotopic equilibrium has been achieved. Metabolic pools have a binomial distribution of 18O whereas nonmetabolic pools exhibit negligible 18O labeling. The application and limitations of this approach are illustrated with data from isolated toad retinas and human platelets. At 22 degrees C, the time constant of ATP hydrolysis in the dark-adapted toad retina is about 30 s. Under these conditions, over 80% of the retinal ATP is involved in high-energy phosphate metabolism. It is calculated that when cGMP metabolic flux in the photoreceptors is maximally stimulated by light, it accounts for 10% of the ATP utilization by the entire retina. The time constant of ATP hydrolysis in human platelets at 37 degrees C is approximately 1 s, and 60% of the platelet ATP is involved in energy metabolism. PMID- 2930827 TI - Slow inactivation and reactivation of the K+ channel in squid axons. A tail current analysis. AB - Potassium current inactivation and reactivation in squid axons were measured from tail current amplitudes after voltage clamp prepulses to the potassium equilibrium potential, EK, in seawater containing elevated levels of potassium ion concentration, Ko. Little or no inactivation resulted with prepulses lasting less than 100 ms. Longer pulses caused the current to inactivate in two phases, one between 0.1 and 1 s, and a second phase between 5 and 100 s. Inactivation was incomplete. The time constant of the tail current after a prepulse to EK was independent of pulse duration (0.1-120 s). Inactivation was independent of Ko (10 less than or equal to Ko less than or equal to 300 mM), and it was independent of membrane potential, V, for -40 less than or equal to V less than or equal to 0 mV. Reactivation was measured with a three-pulse protocol. The reactivation time course was sigmoidal with a delay of approximately 100 ms before significant reactivation occurred. These results were described by a model consisting of three inactivated states arranged in a linear sequence. The rate constants of the model are of the form (A + B exp (CV), or 1/(A + B exp (CV], which are required to describe the non-inactivating conductance component. PMID- 2930828 TI - Effects of various anions on the Raman spectrum of halorhodopsin. AB - Resonance Raman experiments were conducted to probe and understand the effect of various anions on halorhodopsin. These included monoatomic anions Cl- and Br-, which bind to the so-called halorhodopsin binding sites I and II, and polyatomic anions NO3- and ClO4-, which bind to site I only. The two types of ions clearly show different effects on the vibrational spectrum of the chromophore. The differences are not localized to the Schiff base region of the molecule, but extend to the chromophore structure-sensitive fingerprint region as well. We find that the protonated Schiff base frequency is at 1,633 cm-1 for Cl- and Br- ions, as reported previously for Cl-. However, we find that two Schiff base frequencies characterize halorhodopsin upon binding of the polyatomic anions. One frequency lies at the same location as that found for the monoatomic anions and the other is at 1,645 cm-1. Halorhodopsin with bound NO3- and ClO4- thus may consist of two heterogeneous structures in equilibrium. This heterogeneity does not seem to correlate with a retinal isomeric heterogeneity, which we can also demonstrate in these samples. The results suggest that anions binding to site I do not bind to the Schiff base directly, but can influence chromophore and/or protein conformational states. PMID- 2930829 TI - Analysis of equatorial x-ray diffraction patterns from skeletal muscle. AB - Some of the factors that affect the intensities and the phases of the first five equatorial x-ray reflections from skeletal muscle are studied by simplified models describing axially projected mass distributions in unit cells. Examples of mass distributions that produce various phase combinations and intensities are presented. Effects due to radial movement of crossbridges and those due to mass transfer between the thick filament and the thin filament regions are compared. In addition, the study suggests that some features in the reconstructed filament structures could be due to the consequences of limited resolution. PMID- 2930830 TI - Structures of actomyosin crossbridges in relaxed and rigor muscle fibers. AB - It was shown previously that a significant fraction of the myosin crossbridges is attached to actin in the skinned rabbit psoas fibers under relaxed conditions at low ionic strength and low temperature (Brenner, B., M. Schoenberg, J. M. Chalovich, L. E. Greene, and E. Eisenberg. 1982. Proc. Natl. Acad. Sci. USA. 79:7288-7291; Brenner, B., L. C. Lu, and R. J. Podolsky. 1984. Biophys. J. 46:299 306). In the present work, the structure of the attached crossbridges in the relaxed state between ionic strengths of 20 and 100 mM, as compared with that in the rigor state, is further examined by equatorial x-ray diffraction. Mass distributions projected along the fiber axis are reconstructed based on the first five equatorial reflections such that the spatial resolution is 128 A. The fraction of crossbridges attached under relaxed conditions are estimated to be in the range of 30% (at 100 mM ionic strength) and 60% (at 20 mM). The reconstructed density maps suggest that in the relaxed state, upon attachment the part of the crossbridge that centers around the thin filament is small, and the attachment does not significantly alter the center of mass of the myosin head distribution around the thick filament backbone. In contrast, accretion of mass in the rigor state occurs in a wider region surrounding the thin filament. In this case, mass in the surface region of the thick filament backbone is shifted slightly outward, probably by approximately 10 A. A schematic model for interpreting the present data is presented. PMID- 2930831 TI - Determination of bilayer membrane bending stiffness by tether formation from giant, thin-walled vesicles. AB - The curvature elastic modulus (bending stiffness) of stearoyloleoyl phosphatidylcholine (SOPC) bilayer membrane is determined from membrane tether formation experiments. R. E. Waugh and R. M. Hochmuth 1987. Biophys. J. 52:391 400) have shown that the radius of a bilayer cylinder (tether) is inversely related to the force supported along its axis. The coefficient that relates the axial force on the tether to the tether radius is the membrane bending stiffness. Thus, the bending stiffness can be calculated directly from measurements of the tether radius as a function of force. Giant (10-50-microns diam) thin-walled vesicles were aspirated into a micropipette and a tether was pulled out of the surface by gravitational forces on small glass beads that had adhered to the vesicle surface. Because the vesicle keeps constant surface area and volume, formation of the tether requires displacement of material from the projection of the vesicle in the pipette. Tethers can be made to grow longer or shorter or to maintain equilibrium by adjusting the aspiration pressure in the micropipette at constant tether force. The ratio of the change in the length of the tether to the change in the projection length is proportional to the ratio of the pipette radius to the tether radius. Thus, knowing the density and diameter of the glass beads and measuring the displacement of the projection as a function of tether length, independent determinations of the force on the tether and the tether radius were obtained. The bending stiffness for an SOPC bilayer obtained from these data is approximately 2.0 x 10(-12) dyn cm, for tether radii in the range of 20-100 nm. An equilibrium relationship between pressure and tether force is derived which closely matches experimental observation. PMID- 2930832 TI - System analysis of Phycomyces light-growth response: madC, madG, and madH mutants. AB - The light-growth response of Phycomyces has been studied further with the sum-of sinusoids method in the framework of the Wiener theory of nonlinear system identification. The response was treated as a black box with the logarithm of light intensity as the input and elongation rate as the output. The nonlinear input-output relation of the light-growth response can be represented mathematically by a set of weighting functions called kernels, which appear in the Wiener intergral series. The linear (first-order) kernels of wild type, and of single and double mutants affected in genes madA to madG were determined previously with Gaussian white noise test stimuli, and were used to investigate the interactions among the products of these genes (R.C. Poe, P. Pratap, and E.D. Lipson. 1986. Biol. Cybern. 55:105.). We have used the more precise sum-of sinusoids method to extend the interaction studies, including both the first- and second-order kernels. Specifically, we have investigated interactions of the madH ("hypertropic") gene product with the madC ("night blind") and madG ("stiff") gene products. Experiments were performed on the Phycomyces tracking machine. The log-mean intensity of the stimulus was 6 x 10(-2) W m-2 and the wavelength was 477 nm. The first- and second-order kernels were analyzed in terms of nonlinear kinetic models. The madH gene product was found to interact with those of madC and madG. This result extends previous findings that themadH gene product is associated with the input and the ouput of the sensory transduction complex for the lightgrowth response. PMID- 2930833 TI - Simulation of concentration polarization in electrokinetic processes by network thermodynamic methods. AB - Simple techniques of network thermodynamics are used to study the influence of concentration polarization on the determination of electrokinetic properties of physical and biological membrane systems. A network model of the polarization phenomenon resulting from discontinuities in transport numbers between the membrane and their adjacent solutions is proposed. The concentration profiles and potential drop across the membrane in plugs of monodisperse polystyrene particles and in giant algal cells have been simulated using the electrical circuit simulation program SPICE. PMID- 2930834 TI - Calorimetric studies of the effects of cholesterol on the phase transition of C(18):C(10) phosphatidylcholine. AB - Differential scanning calorimetry (DSC) has been employed to study the effects of cholesterol on the phase transition of C(18):C(10) phosphatidylcholine (C(18):C(10)PC). C(18):C(10)PC is an asymmetric mixed-chain phosphatidylcholine known to form mixed-interdigitated structures below the transition temperature and form partially interdigitated lipid bilayers above the transition. Three types of samples were used. The treated sample is the lipid dispersion that had undergone three freeze-thaw cycles and stored at 4 degrees C for more than 48 h. The untreated sample was made by vortexing the dry lipid in 50 mM KCl, without the above-mentioned pretreatment. The cold-treated sample was prepared by incubating the treated sample at -20 degrees C for 15 d. There is no apparent difference in the DSC curves between the treated and cold-treated samples. The data derived from the treated samples seem to be more reproducible. The DSC curves between the cholesterol/C(18):C(10)PC and cholesterol/symmetric diacylphosphatidylcholine mixtures are different in three aspects: overall appearance, the cholesterol dependence of delta H, and the effect of cholesterol on the maximal transition temperature Tm, the onset temperature To, and the completion temperature Tc. for both the treated and untreated samples, the total enthalpy change delta H of the phase transition of C(18):C(10)PC decreases with increasing cholesterol content, approaching zero at approximately 25 mol%. This level is lower than the total enthalpy changes reported previously for the cholesterol/symmetric diacylphosphatidylcholine mixtures. Both the heating and cooling thermograms show that Tm, To, and Tc decrease with increasing cholesterol content. The decreasing rates of these temperatures with cholesterol are in the neighborhood of -0.24 degree per mol% of cholesterol. This value is greater than those reported previously for cholesterol/symmetric diacylphosphatidylcholine mixtures. The phase transition between interdigitated lipid bilayers appears to be more sensitive to cholesterol than that between noninterdigitated lipid structures. The formation of highly ordered interdigitated lipid bilayers requires stringent structural conditions such as specific chain length differences and high molecular order. Apparently, in the presence of cholesterol, these stringent structural conditions are no longer satisfied. It is likely that cholesterol causes a local disordering effect on the gel phase of C(18):C(10)PC and that as a consequence the physical state of the gel phase changes continuously with the cholesterol content. The implication of the present study is that cholesterol may have a function in preventing lipids from forming highly ordered interdigitated structures in natural membranes. PMID- 2930835 TI - Surface charge density of purple membrane. PMID- 2930836 TI - Differences in the expression of alkaline phosphatase mRNA in chronic myelogenous leukemia and paroxysmal nocturnal hemoglobinuria polymorphonuclear leukocytes. AB - Paroxysmal nocturnal hemoglobinuria (PNH) and the stable phase of chronic myelogenous leukemia (CML) are the two hematological conditions known to be associated with low levels of leukocyte alkaline phosphatase (LAP) activity in peripheral blood polymorphonuclear cells (PMN). LAP mRNA levels were determined in PMN from PNH and CML patients by RNA blotting analysis. In CML, LAP mRNA is undetectable, suggesting either decreased transcription or rapid degradation of the message. Contrarily, in PNH normal or high levels of LAP mRNA are present. This latter finding supports the concept of a deficit in the anchorage of the protein to the plasma membrane through the glycolipid pathway, even though other post-transcriptional mechanisms could be involved. PMID- 2930837 TI - Acute promyelocytic leukemia: treatment results during a decade at Memorial Hospital. AB - Fifty-seven adult patients with acute promyelocytic leukemia (APL) were treated between 1974 and 1984 with daunorubicin (DNR) or 4-(9 acridinylamino)methanesulfan-m-anisidide (AMSA) in combination with arabinosylcytosine (Ara-C) and 6-thioguanine (TG); they also received prophylactic heparin. Forty-one patients (72%) achieved complete remission (CR), including 11 of 12 patients who received the AMSA-containing regimen. The incidence of early fatal hemorrhage was 14%, lower than that of earlier studies or other published reports. Elevated WBC and serum lactate dehydrogenase levels at diagnosis were associated with an increased incidence of life-threatening hemorrhage and shorter remission duration. Advanced age was an unfavorable prognostic factor for male patients. Both DNR and AMSA in combination protocols are effective treatments for APL. The incidence of CR is similar to that achieved in other types of acute nonlymphoblastic leukemia (ANLL) with the same protocols, but the median duration of remission is significantly longer in APL (24 v 9 months) and the percentage of remissions longer than 60 months is also higher in APL (35% v 5%). PMID- 2930838 TI - Human vascular endothelial cells express a membrane protein complex immunochemically indistinguishable from the platelet VLA-2 (glycoprotein Ia-IIa) complex. AB - Endothelial cells express surface molecules that are involved in cell-matrix interaction, including the vitronectin receptor and the fibronectin receptor, both members of a family of cell adhesion receptors (integrins). Here we provide evidence that endothelial cells express a membrane molecule, indistinguishable from the platelet VLA-2 complex, which is a collagen receptor and a member of the integrin family. To identify this endothelial molecule, we have used a monoclonal antibody, CLB-10G11, which recognizes the VLA-2 complex from platelets. The molecule recognized by CLB-10G11 from endothelial cells was characterized as follows. (1) The monoclonal antibody precipitated two proteins from surface labeled endothelial cells that corresponded to the platelet VLA-2 subunits (glycoprotein Ia and IIa) as judged by one-dimensional sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and two-dimensional nonreduced/reduced SDS-PAGE. (2) Preclearing of endothelial cells with monoclonal antibody A-1A5, an antibody that is directed against the common VLA beta subunit, removed all the CLB-10G11-binding material. (3) Crossed immunoelectrophoresis revealed that CLB-10G11 recognizes a single precipitation arc from either platelets or endothelial cells. Analysis of these two cell types in one gel again revealed one precipitation arc. The antigen of either cell type, recognized by CLB-10G11 could be precipitated by either polyclonal antiplatelet or polyclonal antiendothelial cell antiserum. Hence, it appears that endothelial cells express at least three different surface molecules (the vitronectin receptor, the fibronectin receptor and a collagen receptor), which may play an important role in controlling the anchorage of endothelial cells to the extracellular matrix. PMID- 2930839 TI - The bcr gene in Philadelphia chromosome positive acute lymphoblastic leukemia. AB - In chronic myelogenous leukemia (CML) and in a percentage of childhood and adult acute lymphoblastic leukemia (ALL) the Philadelphia (Ph') chromosome is present in the leukemic cells of patients. This chromosome is the result of a reciprocal translocation between chromosomes 9 and 22. In CML the break on chromosome 22 occurs within the major breakpoint cluster region (Mbcr) of the bcr gene. In this study, we report on the examination of DNAs from nine Ph'-chromosome positive ALL patients for rearrangements within the bcr gene using Southern blot analysis. Of nine patients having a karyotypically identifiable Ph'-chromosome, only five exhibited rearrangements of the bcr gene. This could indicate that in ALL, chromosome 22 sequences other than the bcr gene are involved in the Ph' translocation. Within the group of Ph'-positive ALL patients having a bcr gene breakpoint, a correlation appears to exist between the age of the patient and the location of the breakpoint within the gene: all or the vast majority of pediatric patients analyzed to date do not have a Mbcr breakpoint as found in CML and in adult ALL. PMID- 2930840 TI - Ph1-positive, bcr-negative acute leukemias: clustering of breakpoints on chromosome 22 in the 3' end of the BCR gene first intron. AB - About 50% of the Philadelphia-positive acute leukemias undergo molecular rearrangements outside the now classical bcr sequence (or M-BCR-1) rearranged in chronic myeloid leukemia (CML). Most of the breakpoints on chromosome 22 have been shown to be clustered in a 10.8-kb region of the first intron of the BCR gene (called bcr2 or m-BCR-1). In this report we examined two cases of Ph1 acute lymphoblastic leukemia in adult patients that exhibited breakpoints in a 5-kb segment of the BCR gene first intron, 16 kb upstream of the previously described cluster, suggesting the possibility of a second minor breakpoint cluster. In addition, the breakpoints on chromosome 9 were located in a region just 5' of the c-abl exon la. PMID- 2930842 TI - Megakaryocytopoiesis. PMID- 2930841 TI - Antibodies to thrombin in postsurgical patients. PMID- 2930843 TI - The relationship between megakaryocyte ploidy and platelet volume. PMID- 2930844 TI - Localization of megakaryocytes in the bone marrow. PMID- 2930845 TI - Megakaryocytopoietic regulation: the forest and the trees. PMID- 2930847 TI - Modulation of megakaryocytopoiesis by erythropoietin via a direct effect of the hormone on progenitor cells. PMID- 2930846 TI - Erythropoietin and megakaryocytopoiesis. AB - To determine if erythropoietin influences megakaryocytopoiesis, the purified recombinant human hormone (rEpo) was added to serum-free liquid cultures of murine marrow. A dose-related increment in acetylcholinesterase (AchE) production was observed. To assess if increments in this relatively megakaryocyte-specific enzyme marker were mediated by a direct hormone-megakaryocyte interaction rather than via an accessory cell population, rEpo was added to cultures of isolated single megakaryocytes. A significant, dose-related increase in cell size was noted in the presence of the hormone, accompanied by a high probability of an increase in cellular DNA content. The data show that rEpo does directly influence some aspects of megakaryocytic maturation, although the physiologic significance of this effect remains unknown. PMID- 2930848 TI - Signal transduction events in in vitro megakaryocytopoiesis. PMID- 2930849 TI - Animal models with inherited hematopoietic abnormalities as tools to study thrombopoiesis. PMID- 2930850 TI - On the quest for lineage specific markers for the diagnosis of megakaryoblastic leukemia. PMID- 2930851 TI - Elutriation for isolation of megakaryocytes. AB - Successful isolation of guinea pig megakaryocytes in large numbers was first achieved with a combination of techniques, taking sequential advantage of the low relative densities and large diameters of most megakaryocytes. Several laboratories have made minor improvements, but this approach retains the disadvantage of losing a significant fraction of the megakaryocyte population, the small immature ones. Counterflow centrifugal elutriation has been shown to eject cells from a chamber progressively, according to their sizes. Because almost all the megakaryocytes are bigger than the other marrow cells, the megakaryocytes can be retained while rejecting the contaminants. With this technology, yields of 1.4-2.0 x 10(6) megakaryocytes from one guinea pig are routine, recoveries have been 93%-94% of the input number of megakaryocytes, and final purities now average 72%. A split-specimen comparison with our previous method found elutriation to provide much greater yield and recovery with at least as great a purification as the density-velocity combination. This new technique was easily adapted to isolation of megakaryocytes in single aspirates from normal human marrow. Fifty-fold purification with near total recovery and a yield of 27,000 megakaryocytes per donor allows easy and reliable cytologic studies. Elutriation appears to be the current method of choice for isolation of megakaryocytes. PMID- 2930852 TI - Elutriation for isolation of megakaryocytes. PMID- 2930853 TI - Mechanisms of platelet production. PMID- 2930854 TI - Incorporation of a circulating protein into alpha granules of megakaryocytes. AB - In order to determine whether or not proteins circulating in plasma can be incorporated into megakaryocytes and platelets, horseradish peroxidase (HRP) was injected intravenously into guinea pigs and these cells were examined for uptake by cytochemistry and electron microscopy. Enriched samples of megakaryocytes enabled ultrastructural analysis of large numbers of these rare bone marrow cells. In megakaryocytes, more than 50% of alpha granules contained HRP between 75 minutes and 7 hours after injection. At 24 hours, 25% of the megakaryocyte granules were peroxidase positive; less were so by 48 hours and none at 4 days. Thus, the findings demonstrate that a circulating protein can be endocytosed by megakaryocytes and rapidly packaged into alpha granules. A precipitous drop in circulating platelet numbers was observed 45 minutes after injection. At this time, circulating platelets showed the tracer only on the platelet plasma membrane, and none in platelet granules. Platelet numbers increased to 35% by 7 hours and only the platelet granules contained HRP. These platelets secreted the HRP stored in granules in response to thrombin. Unfortunately, our present studies do not allow us to distinguish between direct endocytosis by the platelet and/or shedding of new platelets from recently labeled megakaryocytes. Our studies are the first to demonstrate an endocytic pathway by which megakaryocytes can incorporate a circulating protein into alpha granules. An important physiologic implication of this endocytic pathway is the possible origin of certain alpha granule proteins from plasma. PMID- 2930855 TI - The relationship of alpha granules to the membrane systems of platelets and megakaryocytes. PMID- 2930856 TI - Time-related shape control modifications during erythrocyte storage with additive solutions. AB - To obtain more detailed information on the reversibility of shape alterations in blood bank stored erythrocytes, we have studied shape recovery after chemical crenation and rheological properties in 8 PAGGS-sorbitol preserved erythrocyte concentrates during a five week storage period under blood bank conditions. Our results show that red cell capability to regain a normal discoid shape after chemical crenation decreases during storage but is not lost over a five week period. Moreover there is a significant but weak correlation between red cell ATP content and both shape recovery capability and viscosity. Our results confirm suspicious that red cell shape perturbations following blood bank storage are widely reversible. Two different mechanisms may be involved in reducing shape recovery capability during storage, namely an ATP-dependent mechanism and an energy-independent one. The energy dependent mechanism may be preserved by the previous addition of solutions which maintain higher energy levels during storage. PMID- 2930857 TI - Increased incidence of hepatitis B markers in children with sickle-cell anemia. AB - Screening of 143 children 6 months to 12 years of age with sickle-cell anemia showed that 39.2% were HBsAg-positive as compared with 19.3% of the 161 control children of the same age group, who had Hb genotype AA (chi 2 = 14.7383; P less than 0.001). Fifty percent of the HbSS children under the age of 1 year were HBsAg-positive as opposed to 4.3% of the control group (chi 2 = 9.1955; P less than 0.001), while 28.6% of patients were HBsAg-positive at the age of 4 years compared with only 7.4% of the controls at the same age. The incidence of anti HBc in both groups was similar. Markers of HBV infection (HBsAg + anti-HBc) were, however, on the whole higher in the patients with sickle-cell anemia [88/118 (74.6%)] than in the controls [54/88 (61.3%; P less than 0.005)]. PMID- 2930858 TI - Correlations of electrocardiography and echocardiography in assessment of left ventricular wall thickness in hypertensive patients. AB - Posterior wall thickness (PW) and interventricular septal thickness (IVS), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), ejection fraction (EF) and left ventricular mass (LV mass) were determined by the echocardiogram. These were compared with the sum of the S wave in lead V1 plus the R wave in lead V6(SV1 + RV6) determined by electrocardiogram (ECG) in 21 hypertensive patients. A significant increase in PW (p less than 0,05), IVS (p less than 0.05) and LV mass (p less than 0.01) was found in all the 21 patients. PW was highly correlated with SV1 + RV6(r = 0,76; p less than 0.01) in 12 patients. LV mass was correlated with LVEDD (r = 0,60; p less than 0.05) and LVESD (r = = 0.66; p less than 0.05) in the same patients mentioned before. We conclude that LV mass increases early in hypertensive patients and can be better assessed by echocardiography than ECG. The PW has a greater influence on the SV1 + RV6 sum than the echocardiographically assessed IVS. PMID- 2930859 TI - Double island latissimus dorsi muscle-skin flap for through-and-through defects of the forefoot. AB - A case of osteomyelitis of the forefoot is presented. The defect was unusual in that both medial and lateral wounds were larger than the osseous tunnel that connected them. A double skin island latissimus dorsi vascularized flap utilizing larger skin islands than the diameter of the muscle pedicle perfusing them allowed for wound closure. The high density of musculocutaneous perforating vessels of this muscle-skin unit permit such a technique to be safe and effective. PMID- 2930860 TI - Closure of the donor defect for breast reconstruction with rectus abdominis myocutaneous flaps. AB - The abdominal muscles not only constitute a multidirectional cinch that holds the abdominal contents in place, but they also determine the flexion and rotational movements of the trunk. The rectus is mainly responsible for flexion and the obliques are responsible for rotating the trunk. It is therefore important to maintain the tone and direction of pull of the oblique muscles. The key to closure of the fascial defect is to replace the same area of anterior rectus fascia (tendon of both obliques and transversus muscles) as has been removed with the rectus abdominis flap pedicle. This replacement, done with a double Merselene mesh, should extend up to the costal margin and should be of the same width as the fascia taken with the muscle pedicle. This technique was drawn from experience with 186 patients. Of these, 31 were simply approximated, and 43 percent developed weakness, bulging, or hernias, of which 5 required secondary repair. A total of 155 patients were closed with Merselene mesh, and only 4 percent developed bulging that was later repaired and attributed to technical mistakes. There were two cases of infection and three cases of exposed mesh due to necrosis (mesh did not need removal). Seromas were common (14 percent), but the incidence was reduced to 5 percent after tacking stitches were done from the mesh to the subcutaneous fascia. PMID- 2930861 TI - Psychological impact of sport on disabled athletes. PMID- 2930862 TI - Influence of early beta-endorphin treatment on the behavior and reaction to beta endorphin in the adult male rat. AB - A study was made of the influence of early exposure to beta-endorphin (beta-END) on the adult behavior and response to beta-END in male rats. beta-END was given during a neonatal period, at 1-5 days of age (1 microgram/animal/day s.c.). Recordings of the development of home-nest-orientation ability, body weights, and sex-specific approach behavior showed that the early beta-END treatment did not have debilitating or other non-specific effects. The early beta-END treatment did cause significant changes in the establishment of the adult pattern of sex specific approach behavior. Copulatory behavior was not apparently influenced. Intracerebroventricular injection of beta-END (1 microgram) at an adult age induced changes in exploratory and copulatory behaviors and in the pattern of sex specific approach behavior. The reaction to this treatment with respect to components of socio-sexual behavior differed significantly between males treated early with beta-END and their corresponding controls. No differences were observed in behaviors in the exploratory test situation. It is concluded that early beta-END treatment in rats influences components of socio-sexual behavior and the response to exogenous beta-END in adulthood. PMID- 2930863 TI - Posterior hypothalamic deafferentation abolishes the amnestic effect of electroconvulsive shock in rats. AB - The amnestic effect of immediate post-training transcorneal electroconvulsive shock ECS (15.0 mA, 60 Hz, 2 sec) on step-down inhibitory avoidance learning (0.5 mA, 60 Hz training footshock) was studied in intact rats and in rats submitted to bilateral surgical transection of the dorsal fornix, to anterior or posterior hypothalamic deafferentation, and in sham-operated animals. Animals were tested for retention 24 hr after training. The amnestic effect of ECS was observed in all groups except in the one with the posterior hypothalamic lesion. Fornix lesioned animals showed a moderate retention deficit which was considerably worsened by the ECS treatment. The results indicate that the amnestic effect of ECS requires integrity of posterior hypothalamic pathways. One possibility is that the amnestic effect of ECS may be mediated by posterior afferent fibers to the hypothalamus acting on hypothalamic opioid systems such as have been previously proposed to play a role in ECS-induced amnesia. PMID- 2930864 TI - Dexamethasone suppresses beta-endorphin in humans. AB - Studies assessing the effect of glucocorticoids on beta-endorphin regulation in man have yielded inconsistent results. As measured by a highly specific beta endorphin assay procedure, plasma immunoreactive beta-endorphin (irB-EP) in six healthy subjects was significantly suppressed, along with cortisol, after a 2 mg oral dose of dexamethasone (DEX) (pre-DEX mean +/- S.E.M. in pg/ml = 15.3 +/- 2.0, post-DEX = 9.1 +/- 0,5 t = 3.46, p less than 0.01) but not after placebo (pre-placebo = 17.8 +/- 2.9, post-placebo = 17.2 +/- 1.5, t = 0.27). A less specific B-EP assay system, which yielded spurious irB-EP values (102 +/- 2.3 pg/ml) in plasma stripped of B-EP silicic acid, did not detect this DEX-induced change in plasma irB-EP levels (pre-DEX = 119 +/- 9.3, post-DEX = 112 +/- 5.0, t = 0.64; pre-placebo = 118 +/- 6.4, post-placebo = 119 +/- 4.3, t = 0.32). The methodological artifact encountered in this relatively non-specific assay system appears to account for the failure of an earlier study to demonstrate DEX suppression of irB-EP in man. PMID- 2930865 TI - Lidocaine kindling is accompanied by an increase in apomorphine stereotypy and mesolimbic dopamine D2 receptor density. PMID- 2930866 TI - Endometriosis detection by US with laparoscopic correlation. AB - Endometriosis is a common cause of female infertility. It may affect as many as 40% of infertile women and may be the sole contributing factor to infertility in 15%. A study was undertaken to determine the usefulness of the routine pelvic ultrasound (US) examination in the detection of endometriosis by correlating pelvic US findings with laparoscopic findings in 85 patients who underwent both examinations. Forty-eight patients (56.5%) had no laparoscopic evidence of endometriosis, and 37 patients (43.6%) had endometriosis. Eight of the patients had abnormal sonograms; of these patients, only four had sonographic abnormalities that corresponded to laparoscopically identified endometriosis. Thus, US was successful in detecting endometriosis in only four (10.8%) of 37 patients. US is neither sensitive nor specific in diagnosing endometriosis. Furthermore, we believe that US does not have a significant role in the diagnosis or management of endometriosis in patients in whom a pelvic mass or other obvious pelvic abnormality is not suspected. PMID- 2930867 TI - Analysis of relaxation in the evaluation of ventricular function of the heart. PMID- 2930868 TI - [Inhibitors affecting synthesis and intracellular translocation of glycoproteins as probes]. PMID- 2930869 TI - [99mTc methylene diphosphonate bone scans in primary hyperparathyroidism]. PMID- 2930870 TI - [Echography in the diagnosis of spontaneous hematoma of the rectus muscle]. AB - After a brief explanation of the pathogenesis and of the clinical picture of spontaneous rectus muscle hematoma, the Authors describe 9 diagnosed cases by ultrasonography. The various echographic appearances of this disease are described and the importance of ultrasonography for a correct diagnosis and to avoid unnecessary laparotomy is emphasized. PMID- 2930871 TI - [Lumbar arthrodesis: results after more than 10 years]. AB - Two hundred and seventy four patients had a lumbar spine fusion between 1949/1971. Seventy-five of them were available for review more than 10 years after the procedure. There were twenty spondylolisthesis, forty-eight degenerative discopathies, six cases of Pott's disease and one benign tumour. All the patients had been treated conservatively before the surgical procedure for an average of 7 years and were still complaining of chronic low back pain. All the cases reviewed had fused. The functional results were not related to the surgical technique, which varied during this period: eight posterior mid-line grafts, seventeen interbody fusions and fifty combined anterior and posterior approaches sometimes used because of a primary failure of fusion and no postero-lateral fusions. The average follow-up was 13 years with a range from 10 to 26 years. The clinical results were satisfactory in 74 p. 100 of the cases. There were thirteen failures. Seven of these patients had been operated on before the era of systematic preoperative discography and psychological evaluation and the failure was primary. Other failures were observed at about the tenth post-operative year. The results were better in spondylolisthesis with isthmic lesions, rather than in degenerative spondylolisthesis. They were better in pure low back pain than when the pain associated with sciatica. They were better when fusion was limited to one or two levels. Radiographs ten years after the procedure frequently showed evidence of degenerative lesions of the disc above the level of the fusion and, at the same time, some slipping of the upper vertebra. Fortunately, there was no correlation between the radiological appearances and the clinical results. PMID- 2930872 TI - [Coronary artery angioplasty using the Gruntzig technic. Development of the methodology and initial results at the Hospital de la Santa Creu i Sant Pau]. PMID- 2930873 TI - [Percutaneous transluminal coronary angioplasty. Initial experience with the steerable technic at the Hospital Bellvitge-Princeps d'Espanya ]. PMID- 2930875 TI - [Intraluminal coronary angioplasty. A new milestone in the technological progress of cardiology]. PMID- 2930874 TI - [Coronary angioplasty. Initial experience at the Centro Ramony Cajal]. PMID- 2930876 TI - [Percutaneous transluminal coronary angioplasty in the solitary lesion. Results and complications]. PMID- 2930877 TI - [Percutaneous transluminal coronary angioplasty in patients with multiple coronary involvement. Results and complications]. PMID- 2930878 TI - [Percutaneous transluminal coronary angioplasty. Improvement of results with experience]. PMID- 2930879 TI - [The urgency of coronary angioplasty in unstable angina]. PMID- 2930880 TI - [The risk of percutaneous transluminal coronary angioplasty. Reflections of a cardiac surgeon]. PMID- 2930881 TI - [Pathological anatomy of coronary dilatation by transluminal angioplasty. Report of a case and review of the literature]. PMID- 2930882 TI - [Evaluation of the exercise test with thallium for the clinical follow-up of patients undergoing percutaneous transluminal coronary angioplasty]. PMID- 2930883 TI - [The role of the cardiac surgeon in percutaneous transluminal coronary angioplasty. Results at the Hospital de la Santa Creu i Sant Pau]. PMID- 2930884 TI - [Epidemiological aspects of percutaneous transluminal coronary angioplasty. How to set up a prospective study]. PMID- 2930885 TI - [Percutaneous transluminal coronary angioplasty. Special report for the Health Council of Catalonia. Indications, demand, current state of the technology, accreditation, productivity and organizational implications and costs. Working Group on the Assessment Commission for Advanced Medical Technology of the General Directorate of Health Planning and Organization]. PMID- 2930886 TI - [Cost of percutaneous transluminal angioplasty in a tertiary hospital in our area]. PMID- 2930887 TI - Utilization of cellobiose and D-glucose by Clostridium thermocellum ATCC-27405. AB - Cultures of Clostridium thermocellum ATCC-27405, maintained on cellulose and not adapted to grow on glucose utilize cellobiose preferentially over D-glucose, and are only able to initiate growth on D-glucose when the cellobiose has been exhausted from the growth medium. However, D-glucose is the carbon source preferentially utilized when cultures of this microorganism, previously adapted for growth on glucose, are transferred to a medium with equivalent concentrations of both sugars. One reason for the preferential utilization of glucose over that of cellobiose might be the competitive inhibition of cellobiose phosphorylase by intracellular glucose accumulation. When in the glucose-adapted cultures the pressure to grow on glucose as the sole carbon source is again released, both sugars can be simultaneously utilized. PMID- 2930888 TI - Infant stimulation of the handicapped child in a hospital setting. PMID- 2930889 TI - Circulating endogenous opioids and ventilatory response to CO2 and hypoxia. AB - The role of endogenous opioids in the control of breathing is not yet well defined. Radioimmunoassays that measure beta-endorphin (BE) and met-enkephalin (MET) having recently become available, we decided to evaluate the possible relation between the blood levels of these two opioids and different hypercapnic and hypoxic ventilatory responses observed in a group of normal subjects. Ventilatory response to hypercapnia (n = 9) and to hypoxia (n = 7) were determined by classical rebreathing methods. A voluntary isocapnic normoxic hyperventilation test was used as a control. Basal levels of BE and MET did not correlate with the magnitude of the ventilatory response to either hypercapnia or hypoxia. Moreover, BE and MET levels measured repeatedly up to 30 min after each test did not change significantly. We conclude that circulating endogenous opioids do not play a role in the control of breathing in normal humans. These results do not rule out a possible role for these substances as locally released mediators. PMID- 2930890 TI - [Clinical and genetic aspects of Huntington's disease. Study of 28 patients]. PMID- 2930891 TI - [Lumbago: psychologic aspects]. PMID- 2930892 TI - [Prescriptions in pedodontics: guidelines for use by the general practitioner]. PMID- 2930893 TI - [Relaxation and rehabilitation for the dental spine]. PMID- 2930894 TI - [Orodental complaints in blind children]. PMID- 2930895 TI - [Technic: laparoscopy]. PMID- 2930896 TI - Different inhibition of one and two chain tissue plasminogen activator by a placental inhibitor studied with two tripeptide-p-nitroanilide substrates. AB - The interaction of tissue plasminogen activator derived from a melanoma cell line with a specific plasminogen activator inhibitor from placental tissue, which inhibits urokinase and tissue plasminogen activator but not plasmin, was studied. Tissue plasminogen activator exists in two forms, a one chain and a two chain molecule. It was found that the two enzyme species each form 1:1 complexes with the inhibitor and that the two chain enzyme binds the inhibitor very strongly, Ki = 3 X 10(-10) mol/l, whereas the one chain enzyme forms a much weaker complex, Ki is approximately 10(-7) to 10(-8) mol/l. Substrate hydrolysis is much more efficiently catalysed by the two chain plasminogen activator than by the one chain activator. PMID- 2930897 TI - Effect of combining dentin bonding agents. AB - The wall-to-wall polymerization contraction of a light-cured composite was measured in cylindrical dentin cavities treated with the bonding agents: Scotchbond, Clearfil Bond, Gluma/Scotchbond, Gluma/Silux Enamel Bond or Gluma/Clearfil Bond. Marginal gaps were prevented in 29 out of 30 cases when Gluma was used in combination with Clearfil Bond. This combination mediates a mean bond strength between composite and dentin of 20 MPa. PMID- 2930898 TI - Chloracne, "the hallmark of dioxin intoxication". AB - Clinical experiences and laboratory studies are described involving a population of workers who were exposed in a plant making 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), including a trichlorophenol runaway reaction. Workers were followed for a period of four years, and 30 years later a mortality analysis was done on those exposed to runaway reaction material to determine possible increased risks for causes of death. Subsequently, a morbidity study on 436 employees involving three cohorts was carried out to determine the long-term health effects associated with the production of 2,4,5-T including 2,3,7,8-tetrachlorodibenzo-p dioxin (TCDD). The mortality and morbidity studies demonstrated that the standardized mortality ratio for all causes of death was 69, and for cancer at all sites and cardiovascular disease it was 100 and 68, respectively. The most significant observations emerging from the morbidity study were that 86% of the exposed persons developed chloracne at some time and that 52.7% still had chloracne on examination 20 to 30 years after the initial exposure. There appeared to be no evidence, on a long-term basis, of increased risks for cardiovascular disease, hepatic disease, renal disease, central and peripheral nerve problems, reproductive problems, or birth defects among the exposed and those who had chloracne among the exposed. Studies on the cell kinetics and pathogenesis of chloracne indicate that TCDD induces the modulation of undifferentiated sebaceous gland cells to keratinocytes. This action results in a disappearance of sebaceous glands and substitution of closed comedones and keratin cysts. Production workers have the highest frequency and severity of chloracne and systemic effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2930899 TI - Atrial natriuretic factor ameliorates chronic metabolic alkalosis by increasing glomerular filtration. AB - The kidney maintains the elevated plasma concentration of bicarbonate that occurs in chronic metabolic alkalosis. A reduction in the glomerular filtration rate (GFR) can maintain the filtered bicarbonate load at a normal level so that a normal rate of bicarbonate reabsorption suffices to prevent urinary excretion of this anion. It is also possible that bicarbonate reabsorption might increase so as to maintain the alkalosis if GFR were not reduced. To examine this latter possibility, atrial natriuretic factor was used in alkalotic rats to restore a more normal GFR and to increase the amount of bicarbonate filtered by the glomerulus. Proximal bicarbonate reabsorption remained relatively static. Higher than normal amounts of bicarbonate were then delivered out of the proximal tubule, bicarbonate appeared in the urine, and the plasma concentration of bicarbonate fell. A reduction in GFR is thus necessary for the maintenance of chronic metabolic alkalosis. Normalizing GFR induces bicarbonaturia and initiates repair of the alkalosis. PMID- 2930900 TI - Solitary vertebral body uptake on bone scintigraphy: the "black ivory" vertebrae sign. PMID- 2930901 TI - Atrioventricular septal defects. PMID- 2930902 TI - Patent ductus arteriosus. PMID- 2930903 TI - Interventional techniques in congenital heart disease. PMID- 2930904 TI - [Round table. Professional nursing foresight and responsibility]. PMID- 2930905 TI - [Monocyte function in patients with sickle-cell anemia]. PMID- 2930906 TI - Psychosocial responses to traumatic physical disability. AB - Victims of traumatic physical disability experience disruptions of normal affective functioning. The sense of body image and body ego are altered in ways that are frightening or confusing to the patient. The subjective experience of time becomes present-oriented, with time moving slowly. Grief or depression, clinically distinct responses, may further debilitate the individual. Anxiety, guilt and rage are additional emotional responses. Patients use previously existing coping patterns to manage the crisis of sudden disability. It is not the nature or the severity of the injury that exclusively influences the psychological response, but rather, it is the interaction of the person and the total environment that determines behavior. PMID- 2930907 TI - Management problems associated with Cornelia de Lange syndrome. PMID- 2930908 TI - The surgeon's role in the treatment of acute myocardial infarction. AB - Most acute myocardial infarctions are associated with thrombotic occlusion superimposed on a significant coronary arterial atherosclerotic plaque. Restoration of coronary flow can limit ultimate infarct size if accomplished within 4 to 6 hours of the onset of symptoms. Thrombolytic therapy with intracoronary and intravenous streptokinase or by tissue-specific plasminogen activator is effective as a rapid means of reperfusing infarcting myocardium. Percutaneous coronary angioplasty and surgically constructed bypass grafts can convert a tenuous source of coronary flow to reliable, unrestricted myocardial perfusion. Although acute surgical revascularization can be performed during an evolving infarction, the time restraints imposed by ischemic cellular injury dictate that bypass grafting serve as an adjunct to thrombolytic therapy as a means of preventing rethrombosis and providing global as well as regional revascularization. The vast potential benefit for minimizing morbidity and mortality resulting from quantitative limitation of acute myocardial necrosis mandates scientific evaluation of the new armamentarium directed at medical surgical reperfusion. PMID- 2930909 TI - The stimulus for vasopressin release during laparoscopy. AB - The results of our study have demonstrated raised AVP secretion during laparoscopy, which was stimulated by the maximal increase in IAP. We propose that this relationship is mediated by way of known hemodynamic pathways occurring during laparoscopy involving a reduction in intrathoracic blood volume. PMID- 2930910 TI - An extrapleural approach with rib removal for the eleventh rib flank incision. AB - The transcostal extrapleural flank approach to the kidney requires an understanding of the anatomy of the thoracic and abdominal wall to prevent injury to the pleura and subsequent pneumothorax. Isolation of the intercostal neurovascular bundle, division of the lumbodorsal fascia inferior to the rib bed, and simultaneous dissection of the diaphragmatic insertion along the superior and posterior aspect of the twelfth rib toward the lumbocostal arch are necessary surgical maneuvers. This should be done prior to the release of the diaphragm, exposure of Gerota's fascia and positioning of a flank retractor. Pneumothorax usually results from attempts to separate the pleura from the diaphragm, dissection within the intercostal space rather than along the diaphragmatic insertions, and failure to release fully the diaphragm as far as the lumbocostal arch prior to placement of the retractor. Precise appreciation of the pericostal anatomy allows the urologic surgeon to remain in the extrapleural space during this commonly used flank incision. PMID- 2930911 TI - The collective representation of affliction: some reflections on disability and disease as social facts. PMID- 2930912 TI - [Is coccidiosis in mature cattle an exception?]. AB - An outbreak of coccidiosis in a group of forty Jersey cattle is reported. This group formed part of a population of 200 dairy cattle. Severe infection by Dictyocaulus viviparus occurred prior to this outbreak of coccidiosis. The two clinical pictures were confined to the group of Jerseys, which animals had been imported from Denmark during the previous autumn and winter (1983-1984). PMID- 2930913 TI - The effect of dietary restriction and altered sodium intake on the cardiopulmonary toxicity of monocrotaline pyrrole. AB - Monocrotaline pyrrole (MCTP) is a reactive metabolite of the plant toxin monocrotaline (MCT), which produces pulmonary vascular injury and right ventricular hypertrophy in rats. In this study, the influence of diet restriction on the cardiopulmonary toxicity of MCTP was examined. In rats fed ad libitum, MCTP treatment resulted in increased lung weight, in elevated lactate dehydrogenase (LDH) activity and protein concentration in cell-free bronchopulmonary lavage fluid, and in right ventricular enlargement. Restriction of feed intake to 40% of normal attenuated the increases in lung weight and lavage protein concentration in MCTP-treated rats and abolished the right ventricular enlargement but did not affect the increased lavage LDH activity. In a study of the effect of diet restriction on the survival of MCTP-treated rats, the percentage of diet-restricted animals surviving was significantly higher than that of surviving animals which ate ad libitum through Day 28, but thereafter there was no significant difference between the two groups. Alterations in dietary sodium intake alone did not affect MCTP-induced toxicity. These results indicate that diet restriction partially protects against the cardiopulmonary toxicity due to MCTP, and that this protective effect cannot be explained by changes in salt intake. PMID- 2930914 TI - Mechanism of allyl alcohol toxicity and protective effects of low-molecular weight thiols studied with isolated rat hepatocytes. AB - Freshly isolated hepatocytes from male rats were incubated with allyl alcohol at concentrations up to 2 mM. Allyl alcohol exerted a dose-dependent toxicity on the cells which was inversely related to cellular glutathione (GSH) content and accordingly influenced by stimulation as well as inhibition of GSH synthesis. The toxicity was prevented by inhibitors of alcohol dehydrogenase and augmented by the aldehyde dehydrogenase inhibitor disulfiram, suggesting that the toxic metabolite was the reactive aldehyde acrolein. The pattern of hepatocellular metabolism of allyl alcohol was monitored by high-pressure liquid chromatography (HPLC) analysis. The results suggest that acrolein, which is formed by the activity of alcohol dehydrogenase, preferentially reacts with cellular GSH to form an aldehyde-GSH adduct which subsequently is metabolized to the corresponding acid. In addition, a thiohemiacetal may be produced and subsequently degraded. In cells depleted of GSH, acrolein may react with essential macromolecules and thereby lead to structural and functional derangement and, eventually, irreversible injury. PMID- 2930915 TI - Ultrastructural study of mineral fiber uptake by hepatocytes in vitro. AB - Cellular interactions of a series of fibrous materials were examined by the use of a well established in vitro system. Primary cultures of hepatocytes were exposed to natural attapulgite, synthetic xonotlite and natural sepiolite. Ultrastructural analyses revealed that hepatocytes can engage in the phagocytosis of all 3 types of fibers over an exposure period of 20 h. Attapulgite fibers were found in plasma membrane invaginations, and deeper in the cytoplasm, in vesicles exhibiting various shapes. Xonotlite was also incorporated in plasma membrane invaginations; furthermore, these fibers were present in large vacuoles where they were circumscribed by membranes and appeared somewhat isolated from the cytoplasm. Sepiolite fibers were also taken up by the cells and could likewise be identified in the previously described structures. These observations point to the relevance of the hepatocyte model for investigating the effects of fibrous materials at the cellular level. PMID- 2930916 TI - Which T cells mediate allograft rejection? PMID- 2930917 TI - Kinetics of the MLR response following single donor-specific allogeneic blood transfusions. AB - Prior blood transfusion (BT) confers a significant improvement in transplant survival in recipients (1). However, increased survival across major histocompatibility barriers generally requires the administration of immunosuppressive agents (2-5). The mechanisms by which BT prolongs graft survival have not been fully elucidated. Experimental evidence suggests that suppressor cells (6,7), soluble suppressor factors (8), and blocking antibodies (9) may play a role. PMID- 2930918 TI - Phenotype, activation status, and suppressor activity of host lymphocytes during acute rejection and after cyclosporine-induced unresponsiveness of rat cardiac allografts. AB - Serial changes in phenotype, cell cycle, and functional behavior of lymphocyte subpopulations occurring both during acute rejection in unmodified hosts and in long-surviving heterotopic cardiac allografts in rats treated with cyclosporine (CsA) were studied. Using flow cytometry, RNA and DNA content of cells was examined during various phases of cell activation. In animals acutely rejecting their grafts, numbers of cells infiltrating the grafts and in host spleen in G1 phase (higher RNA content) increased, starting from day 3, and peaked by 5-6 days posttransplantation, and numbers of cells in S/G2/M phase (higher DNA content) remained stable. Similar, although slightly delayed changes were noted in CsA treated recipients. The ratio of T helper (Th) to T suppressor/cytotoxic (Ts/c) phenotype cells infiltrating acutely rejecting grafts by day 3, was 1.6; it inverted abruptly to 0.7 by days 5-6, suggesting a preponderance of Ts/c during the later stages of allograft rejection. Ratio inversion occurred slightly later in host spleen and later in peripheral blood. Similarly, treatment with CsA produced a transient depression of Th, with recovery of the Th: Ts/c ratio during weeks 3-4 following transplantation. Adoptive transfer studies were then performed to investigate the functional significance of the T cell subsets. Survival of test grafts was prolonged significantly (ca. 14 days, P less than 0.001) when cells infiltrating grafts and spleen were transferred during inversion of Th:Ts/c; before that period, test graft survival was shortened in a second-set manner. These experiments suggest that suppressor cells may be responsible for resolution of acute rejection, as well as for host unresponsiveness seen after CsA treatment, and they represent an important homeostatic host mechanism following immunological stimulation. PMID- 2930919 TI - Interleukin-2 production in the neonatal mouse. AB - Neonatal mouse spleen and thymus cells fail to produce interleukin-2 (IL-2) in vitro. In vitro IL-2 production by spleen cells begins to develop between 20 and 27 days of age and reaches adult levels at 40 days of age. Thymus cells do not develop the ability to produce IL-2 in vitro. Addition of neonatal spleen, neonatal thymus, or adult thymus cells to adult spleen cell cultures inhibits IL 2 production. Treatment of the added cells with mitomycin does not abrogate their suppressor activity. Soluble factors, obtained from three-day cell cultures of neonatal spleen, neonatal thymus, or adult thymus also suppress IL-2 production in adult spleen cell cultures. Addition of interleukin-1 raises IL-2 production in adult thymus, neonatal spleen, or neonatal thymus cell cultures slightly, but the IL-2 productivity is still considerably lower than that of adult spleen in the absence of IL-1. The results indicate that suppressor cells for IL-2 production are present in neonatal spleen and thymus. The splenic suppressor cell activity disappears after birth, but thymic suppressor cell activity is retained into adulthood. PMID- 2930920 TI - Requirement for help in the generation of alloantigen-specific helper cells. AB - Control mechanisms that regulate the induction of T helper cells are a key component of conceptual schemes to understand the network of interactions controlling the immune response. In this work, using a sequential three-step culture system, we demonstrate that the generation of the T helper cells that participate in cytotoxic T cell induction is itself dependent on interactions with helper cells. The induction of Ly7- pre-Th requires collaboration with a Th directed Ly1+7+ helper T cell with radioresistant function and the participation of an adherent cell. Th have been generated from thymic responders and from anti Ly7-treated splenic responders, both of which are deficient in Th effector function. Approximately 10-30-fold more help is generated from splenic as compared with thymic pre-Th. Ly7+ Th were required throughout the first 5 days of CTL generation. Using a limiting dilution analysis of pre-Th we have shown that splenic precursor Th are inducible with IL-2, but that the frequency of clones able to deliver antigen-specific help in a CTL response is an order of magnitude lower than the frequency of clones induced by antigen and able to secrete IL-2 reported by others. For reasons described in the discussion, we suggest that Th and IL-2 secretors may be at least partially nonoverlapping subsets. The CTL directed Th effectors induced by IL-2 were analyzed for specificity; 65% of clones were challenge-specific, 29% were crossreactive, and 6% were heteroclitic. We conclude that the Th that participate in the induction of pre-Th coexist with, and bear markers similar to, the Th that act in the induction of pre-T suppressor cells, and of CTL. It seems possible that the control over the class of precursor induced by antigen may be a function of the quantity rather than the quality of helper effectors. PMID- 2930922 TI - Alloreactive T cell responses between HLA-identical siblings. Detection of anti minor histocompatibility T cell clones induced in vivo. AB - Cytotoxic T cell (CTL) clones were isolated from the peripheral blood of a patient 13 days following marrow transplantation from her HLA-identical brother. Nineteen of the clones were specifically reactive with host--but not donor- cells, but one clone was reactive with donor but not host cells. Family studies using the 19 clones showed reactivity patterns consistent with three non-HLA, minor histocompatibility antigens (minor-HA). The frequency of reactivity on a large panel of unrelated cells indicated a relatively limited degree of polymorphism. Each of the clones was restricted in its activity by a class I epitope common to HLA-B7, B27, and B40. These data demonstrate that by clonal analysis it is possible to identify in vivo antidonor and antihost alloreactive CTL clones directed against HLA determinants following marrow transplantation. PMID- 2930921 TI - Assessment of immunocompetence by limiting dilution analysis in long-term T cell depletion chimeras transplanted across the MHC barrier. AB - Chimeras were generated in a system in which donor C57BL/6 bone marrow plus spleen cells were T-cell-depleted prior to transplantation into lethally irradiated DBA/2 recipients. This protocol permits donor lymphohematopoietic engraftment and protects transplanted mice from development of lethal GVHD. The frequencies of alloantigen-specific cytotoxic T cells (CTL) and/or CTL precursors (CTL-P) in the chimera spleens were determined by limiting dilution analysis. This identified a small population of host-reactive CTL-P. The presence of host reactive CTL-P in the absence of detectable anti-host immune response raises questions concerning the maintenance of the tolerant state in chimeras. Using mixtures of chimera and normal C57BL/6 splenocytes we found no evidence by limiting-dilution analysis for regulatory cells capable of dampening antihost immune reactivity in chimera spleens. We next measured the frequency of third party-reactive CTL-P in chimeras. Chimeras displayed low CTL-P frequency by the 30th day posttransplant, which increased 15-21-fold over a five-month interval. Interestingly, both chimeric and irradiated syngeneic reconstituted control mice recovered anti-third-party CTL-P at a similar rate, but CTL-P levels never reached those measured in normal unirradiated control mice, suggesting that the radiation regimen has a long-lasting influence on host immunocompetence. In concomitant experiments we measured third-party CTL generation in MLC. Our findings suggest that measurement of CTL generation in MLC may be a less sensitive assessment of immunocompetence than LDA analysis. Our data also suggest that irradiated T-cell-depleted chimeras may suffer prolonged immunologic deficiencies based on reduced frequencies of alloreactive CTL-P. PMID- 2930923 TI - The possible role of cytotoxic T cells in the mediation of first-set allograft rejection. PMID- 2930924 TI - Dracunculus medinensis presenting as larva migrans. PMID- 2930925 TI - [Isolation and characteristics of a fraction of skeletal muscle sarcoplasmic reticulum enriched with terminal cistern vesicles]. AB - A simple method for rapid isolation of active vesicles of sarcoplasmic reticulum is described. It is characterized by sensitivity to caffeine, high content of calsequestrin and the presence of 30 kDalton protein. The data obtained suggest that this fraction is enriched in vesicles derived from terminal cisterns. PMID- 2930926 TI - Doppler ultrasound in orifice flow. In vitro studies of the relationship between pressure difference and fluid velocity. AB - The validity of an orifice equation (Torricelli's law) which expresses a simple relationship between the pressure difference across an orifice and the maximum fluid velocity in the orifice was tested in vitro. An aqueous suspension of barium sulfate particles with a polymer added to attain variations in viscosity, was forced through orifices which ranged in diameter from 0.4 to 4.7 mm. The pressure difference across the orifice was determined with a transducer and the maximum fluid velocity in the orifice was determined with Doppler ultrasound. Tests were performed at Reynolds numbers, fluid viscosities, and pressure differences that spanned the following ranges: 400-25,000, 1-5 cP, and 3-100 mmHg, respectively. At pressure differences larger than 3 mmHg and fluid viscosity 3 cP (approximate viscosity of in vivo blood), Torricelli's law was demonstrated to be valid for orifice diameters larger than 1.6 mm. The validity of the law was found to be relatively insensitive to variations in orifice length. PMID- 2930927 TI - Whole bladder photodynamic therapy for transitional cell carcinoma of bladder. AB - Our preliminary studies indicate that the bulb-tip technique for whole bladder photodynamic therapy (PDT) illuminates the entire bladder mucosa and is applicable to the management of superficial transitional cell carcinoma of the bladder. This treatment modality may be an option to patients who are failures to other standard treatments. A randomized clinical study is needed to decide on PDT as a primary treatment of choice for transitional cell carcinoma of the bladder. PMID- 2930928 TI - [Organization of the work of the otorhinolaryngologist in the polyclinic]. PMID- 2930929 TI - [Tactics in the surgical treatment of nodular formations in the thyroid gland in an endemic goiter region]. AB - The extrafascial method of operation was used because of high risk of malignization of nodular endemic goiters. The extrafascial hemithyroidectomy with an isthmus is considered by the authors to be the major and minimum operation volume in patients with nodular goiters. The method was used in 76,8% of the patients. In patients with thyroid carcinoma the operation of this volume was fulfilled in 66,5% of cases. PMID- 2930930 TI - [Vestnik Khirurgii I.I. Grekov during the siege of Leningrad]. PMID- 2930931 TI - [The surgical hospital during the siege of Leningrad]. PMID- 2930932 TI - [Comparative informative value of the leukogram and the level of circulating immune complexes in patients with acute appendicitis]. AB - Data of the leukocyte reaction and amount of circulating immune complexes (CIC) in blood serum of patients with acute appendicitis were studied. The determination of CIC is shown to be more informative concerning inflammatory changes in the vermiform process. The method of determination of CIC in blood serum is simple, not time-taking and may be used in urgent surgery as an additional method of diagnosis of acute appendicitis. PMID- 2930933 TI - Chronic eosinophilic dermatitis: a manifestation of a multisystemic, eosinophilic, epitheliotropic disease in five horses. AB - A generalized, chronic, progressive, exfoliative dermatitis in five horses is described. Histologically, the lesion is characterized by a superficial and deep perivascular dermatitis which is eosinophil-rich with a marked lymphocytic and plasmacytic component, accompanied by marked acanthosis and hyperkeratosis. More severe cases progress to a lichenoid pattern with the same cellular composition with focal eosinophilic spongiosis and eosinophilic subcorneal pustules. Clinically, the disease is associated with chronic, severe weight loss and is fulminating. The skin lesions are accompanied by lymphoplasmacytic and eosinophilic infiltrates and formation of eosinophilic granulomas in other epithelial organs, most noticeably the pancreas, in which a chronic, fibrosing pancreatitis develops. Other epithelial organs involved to various degrees are salivary glands, the gastrointestinal system, including the oral cavity and esophagus, biliary epithelium and bronchial epithelium. The etiology of this disease is unknown. PMID- 2930934 TI - Dispersal of Dictyocaulus viviparus larvae from bovine faeces in Ireland. AB - An involvement of Pilobolus species fungus in the dispersal of Dictyocaulus viviparus third stage larvae from dung to surrounding herbage under Irish conditions was investigated. The presence of Pilobolus kleinii on artificial dung pats containing first stage larvae of D viviparus was associated with a 19-fold increase (P less than 0.05) in numbers of third stage larvae recovered from the surrounding herbage. A subjective examination of natural dung pats showed that the presence of Pilobolus species was significantly correlated with hours of bright sunshine (r = -0.5, P less than 0.01), total rainfall (r = 0.41, P less than 0.05) and the height of herbage surrounding the pats (r = 0.31, P less than 0.001). A multiple regression analysis showed that meteorological parameters and the height of surrounding herbage accounted for 38 per cent of the variation in growth of Pilobolus species on dung pats. The incidence of extensive damage to natural dung pats within five days of deposition, caused by biotic factors, another possible cause of D viviparus third stage larvae dispersal, varied from 0 to 92 per cent of the pats depending on their degree of dryness. PMID- 2930935 TI - Pathogenesis of helminths in equines. AB - This review summarizes information on the clinical signs, gross and microscopic lesions associated with nematode and cestode infections and discusses the development of these conditions in the equine host. PMID- 2930936 TI - [Azerbaijan roentgenologists and the Azerbaijan Scientific Research Institute of Roentgenoradiology in World War II]. PMID- 2930937 TI - [Raising the qualifications of x-ray technicians in Leningrad (20 years' experience of the work of the faculty of the Public University for Advanced Training of X-Ray Technicians)]. PMID- 2930938 TI - The influence of antibiotics on the immune system. II. Modulation of fish leukocyte responses in culture. AB - We report the immunomodulating effect of two tetracycline analogues (oxytetracycline and doxycycline) on mitogenic and allogeneic stimulation of carp (Cyprinus carpio) leukocytes in vitro. Both drugs interfered with 3H-thymidine incorporation into the DNA of phytohaemagglutinin-stimulated pronephric leukocytes in a dose-dependent manner. Low concentrations of oxytetracycline delayed the mitogenic response, but did not reduce it. In addition, several other antibiotics were tested for their possible interference with blastogenesis. PMID- 2930941 TI - Genetic analysis of subunit assembly of the tail fiber of bacteriophage T3. AB - Bacteriophage T3 virions have six tail fibers composed of the product of gene 17 (gp17). Each tail fiber is a trimer of gp17 polypeptide. To characterize the assembly process of the tail fiber, temperature-sensitive (ts) mutants of gene 17 (ts17) were analyzed by SDS-polyacrylamide gel electrophoresis and by extract complementation. Newly synthesized gp17 polypeptide chains matured to SDS resistant native trimers with a half time of about 7.5 min at 30 degrees. Although all ts17 mutants had similar plating efficiencies at restrictive temperature (41.5 degrees or 42 degrees), they showed different phenotypes. tsNG75, whose mutation was located in the carboxyl-terminal region of gene 17, was defective in trimer assembly at 41.5 degrees. The ts tail fibers formed at 30 degrees lost the ability to attach to the tail upon treatment at 41.5 degrees. There was a change in temperature sensitivity of tsNG75 tail fibers upon attachment to the tail, suggesting that the tail fiber may change conformation after attachment to the tail. tsNG215 and tsNG169, whose mutation sites were located in the amino-terminal region of gene 17, were not defective in the trimer assembly and attachment to the tail at the restrictive temperature. tsNG215 tail fibers formed at 41.5 degrees appear to be aberrant because they were not active in extract complementation and their attachment to fiberless particles resulted in production of noninfectious phage. Tail fibers produced by cells infected with tsNG169 at the restrictive temperature were active in extract complementation. Phage particles were formed in tsNG169-infected cells at the restrictive temperature. These particles were infectious at the permissive temperature and the mutant was non-infectious only if infection was continued at the restrictive temperature. These phenotypic differences exhibited by different gene 17 mutants may indicate the regions within the gene 17 polypeptide that play a role(s) in the folding and assembly of gp17 and in the biological activity of the mature tail fiber. PMID- 2930939 TI - Nephrotic syndrome: a platelet hyperaggregability state. AB - Nephrotic syndrome characterized by hypoalbuminemia and hyperlipidemia is associated with an increased incidence of thromboembolism and increased platelet hyperaggregability. Although plasma coagulation proteins are also abnormal, changes are too inconsistent to attribute thromboembolic complications to the coagulation cascade alone. Antithrombin III (ATIII) has been shown to be deficient in nephrotic syndrome. There is, however, an increase in alpha 2 macroglobulin. It is clear that platelet to platelet interactions require exposure of platelet fibrinogen receptors, the binding of fibrinogen to these receptors, platelet crossbridging, and subsequent platelet aggregation. Fibrinogen is consistently elevated in nephrotic syndrome. Hyperlipidemia and hypoalbuminemia in nephrotic syndrome increases the availability of thromboxane A2 (TxA2) by increasing the availability of TxA2 precursors and the removal of TxA2 inhibitors. Thromboxane A2 is a known inducer of platelet aggregation probably through the exposure of platelet fibrinogen receptors. Recently, fibronectins a group of adhesive proteins, were implicated in platelet to platelet interactions. Since thrombin increases the expression of platelet surface fibronectin, fibronectin may be involved in thrombus formation in nephrotic syndrome. Thromboembolic formation in nephrotic syndrome is a composite mechanism involving the coagulation cascade, platelet-platelet interactions, and platelet-surface interactions. PMID- 2930940 TI - Weights of the body and cardiac ventricles in pulmonary emphysema. AB - We analysed statistically the association of emphysema, determined on inflation fixed specimens, with the weights of the body and heart, and of the cardiac ventricles, weighed separately, in 170 male and 86 female adult autopsies. The cases were grouped according to the cause of death into cardiovascular, cancer and other deaths. In men the body weight was inversely proportional to the severity of emphysema, but no association existed between the body weight and the cause of death. In male cardiovascular deaths the total heart weight, total ventricular weight and the weight of the left ventricle with the septum were also inversely proportional to the severity of emphysema while this was not true in the other deaths. In male cardiovascular deaths a decrease, and in the other deaths an increase, of the weight of the free wall of the right ventricle was associated with an increasing severity of emphysema. In all male deaths, however, the left to right ratio decreased with an increasing severity of emphysema. Thus, pulmonary emphysema is associated both with a general atrophy, including the myocardium, and a mainly relative right ventricular hypertrophy. An absolute right ventricular hypertrophy, however, seems to accompany emphysema only in the absence of other major cardiovascular diseases. PMID- 2930942 TI - Purification and characterization of gene 17 product of bacteriophage T3. AB - Tail fiber proteins of bacteriophage T3 are encoded by gene 17. By using in vitro complementation for phage assembly as an assay, the product of gene 17 (gp17) was purified to near homogeneity from cells infected with a double mutant of T3 defective in DNA synthesis and head assembly. The purified gp17 consists of a single polypeptide having a molecular weight of 67,000. Electron microscopy of the purified gp17 showed a fiber structure similar to the tail fiber in a virion. The subunit structure of the purified, native gp17 was analyzed by using a crosslinking agent, dimethyl suberimidate. The results indicate that native gp17 is a trimer of gp17 monomer. PMID- 2930943 TI - [Information on the medical support for the main forces of troops in the 1st Byelorussian front in the Warsaw-Poznan operation]. PMID- 2930944 TI - [Sultry weather and oxygen conditions of the atmosphere as exemplified by the Maritime zone of Azerbaijan]. PMID- 2930946 TI - [Content of carcinogenic nitroso compounds in food products]. AB - The data are provided on the content of carcinogenous N-nitroso compounds in foods manufactured in a region with a high gastric carcinoma incidence. It was found that foods under analysis have a high content of carcinogenous nitroso compounds. The foods were also found to contain N-nitrosopiperidine, a carcinogen inducing tumors of the gastrointestinal tract. PMID- 2930945 TI - [Aflatoxin contamination of raw foodstuffs, food products and feeds in the Kazakh SSR from 1981 through 1983]. AB - The time-course of changes in the contamination with aflatoxins of food raw material, foods and feeds, most widespread in Kazakhstan, was studied. It was established that in the republic, there is a high risk of the contamination with aflatoxins of food and feed corn, as well as the combined fodder. This is evidence of the necessity of exercising a more stringent control and carrying out appropriate measures on the part of the sanitary-and-epidemiologie and veterinary services. PMID- 2930947 TI - [Experience in using rapid methods in the work of the nutritional hygienist]. PMID- 2930948 TI - Current concepts in endometriosis. AB - There are no conclusive data available on the incidence or prevalence of endometriosis, yet the notion persists that the frequency of cases has dramatically risen in western societies during the past 25 years. Race, familial predisposition, reproductive history, socioeconomic status, personality type and a historical drop in age at menarche have been posited as risk factors for the complex and as-yet-unclear epidemiology of this disorder. The epidemiology of endometriosis is constrained by the difficulty of the diagnosis. Several analytic concepts from epidemiology, however, could be profitably used to further our knowledge of endometriosis. Included are the case-control study, survival and life-table analyses and correlations of psychologic traits with susceptibility to development of the disease. Though none of these techniques is original or without potential for bias, they may be underutilized in solving the conundrum of endometriosis. PMID- 2930950 TI - Some facets of alternative medicine--today and yesterday. PMID- 2930951 TI - [Ciprofloxacin--a new antibacterial drug]. PMID- 2930952 TI - [Early non-invasive diagnosis of congenital heart defects]. AB - During a period of 22 months there were 84 cases of congenital cardiac malformations diagnosed during the first year of life. This figure corresponds to about 80% of all existing cardiac malformations present in the population covered. Noninvasive measures including echocardiography were sufficient for diagnostic and therapeutic decisions in 75% of the cases. 18% of the malformations had to be operated during the first year of life. There were 8 deaths, 5 of them due to irreparable malformations or underlying conditions. PMID- 2930953 TI - [The clinical picture in shunt nephritis]. AB - Report on three children with hydrocephalus in whom an immune complex nephritis ("shunt-nephritis") had occurred in consequence of an infected atrioventricular shunt. Besides the clinical course, the histological findings which are of particular significance with regard to pathogenesis are discussed as well as the serum complement system on the basis of the laboratory data. Removal of the valve system led to a complete normalization of the laboratory parameters and to a subsidence of the clinical symptoms in all patients. The necessity of a perioperative antibiotic prophylaxis in the insertion of an atrioventricular shunt is explicitly emphasized. Narrow-interval follow-up investigations should enable early detection of cases of shunt nephritis and thus prevent functional residues or even fatalities. Knowledge of this immune complex nephritis is also very important because it is one of the few forms of nephritis in which a causal therapy is available with removal of the infected shunt. PMID- 2930949 TI - Low back pain. AB - Low back pain is one of the most common and costly afflictions of our Society. The majority of adults will have at least one episode of acute low back pain that will likely resolve regardless of treatment. Lumbar spine radiographs are overused and there is little scientific support for many of the therapeutic interventions advocated. Even for those patients with symptomatic herniated disc, only a small fraction will ultimately require surgical intervention. PMID- 2930954 TI - [Unexpected sudden death from natural causes in sports. A pathologic-anatomic analysis and synopsis]. PMID- 2930956 TI - [Striving for movement-induced adaptation--why?]. AB - The skeletal muscle is the most massive organ of the body. Its function is in close interaction with all organs; its activity serves as essential physiological adaptogenic stimulus for the optimization of organ functions. On the basis of an insufficient motion-induced adaptation the spreading lack of motion restricts the efficacy and the stability of vegetatively regulated functions. Morphological and functional adaptive modifications caused by motion may very well be represented at the heart in form of a model. These are objectifiable at a functional, coronary circulatory and cellular level. It can reasonably be started from the fact that an adequate motor activity, which belongs to the biohistorical scheme of the human body, is able to further stability of health, functional capacity and well-being. PMID- 2930955 TI - Chemical characterization of an interleukin-1-inducing substance derived from human mixed leukocyte reactions: IL-1-inducing substance is not gamma interferon. AB - Lymphocyte products released during the human mixed reaction were studied for their ability to stimulate human monocytes to produce endogenous pyrogen and lymphocyte activating factor. These two biological activities are considered properties of the same molecule, called interleukin-1 (IL-1). In these experiments, physical characteristics such as molecular weight, isoelectric point, and binding to concanavalin A (Con A) sepharose were studied under conditions which excluded bacterial endotoxins. Gel filtration revealed molecular weights of approximately 60 and 25 kD with IL-1-inducing activity. Isoelectric points ranged from 5.9 to 6.3. The IL-1-inducing properties of mixed leukocyte reaction supernates did not bind to Con A sepharose. Recombinant human gamma interferon did not induce IL-1 production under various conditions but rather augmented IL-1 induced by endotoxin. In contrast, the mixed leukocyte reaction results in production of lymphokines which directly stimulate IL-1 production in the absence of endotoxins. PMID- 2930957 TI - Genetic markers in Liberia: studies of Glo, AcP, EsD, 6-PGD, Ak, Sub PGM and alpha 1 at polymorphisms. PMID- 2930958 TI - [Dermabrasion--indications, technic, possibilities, complications]. PMID- 2930959 TI - [Immunopathology of the skin and hemosorption]. PMID- 2930960 TI - [Occupational toxicoderma caused by naphthalene]. PMID- 2930961 TI - [Hebra's pityriasis rubra]. PMID- 2930962 TI - [Method of preparing an allergen from uncured polymers in the allergic diagnosis of occupational dermatoses]. PMID- 2930963 TI - [The kallikrein-kinin system in rosacea patients]. PMID- 2930964 TI - [Occupational dermatoses in workers engaged in the manufacture of asbestos cement products]. PMID- 2930965 TI - [Dermatologic morbidity and skin function in miners in deep potassium mines]. PMID- 2930966 TI - [Effectiveness of the combined treatment of true eczema patients with vitamins and sulfide baths at a health resort]. PMID- 2930967 TI - [Effect of detoxifying therapy on the immune complex level and phagocytic system of psoriasis patients]. PMID- 2930968 TI - [Planning of specialized pediatric dental out-patient departments for psychophysically affected youth in the Socialist Republic of Slovenia]. PMID- 2930969 TI - [Postgraduate training in pediatric and preventive dentistry]. PMID- 2930970 TI - [The Leningrad Pasteur Research Institute of Epidemiology and Microbiology during World War II]. PMID- 2930971 TI - [The visiting topical lecture series--an efficient form of postgraduate training of epidemiological health specialists]. PMID- 2930972 TI - [Effectiveness of the selective revaccination of schoolchildren against measles]. AB - The revaccination of 70% of schoolchildren, previously immunized with measles vaccines of 26 different batches with insufficient immunogenic potency, has led to the pronounced and stable increase of immunity in the corresponding groups of children and has decreased measles morbidity among them 20 times. PMID- 2930973 TI - [Electron-cytochemical characteristics of hyperchromic neurons in schizophrenia]. AB - During autopsy of brains from 17 schizophrenic patients and 14 mentally normal subjects the authors studied metabolic characteristics in hyperchromic neurons, using methods of electron cytochemistry. The parameters of plastic and energy metabolism investigated included ribonucleoproteins (RNP), Mg-activated ATPase and succinate dehydrogenase (SDH). Two types of neurons with a different degree of hyperchromia and a decrease in metabolic activity were identified. The type I neurons were characterized by a marked decrease in the activity of the studied enzymes and the number of RNP particles, type II neurons by almost complete absence of enzymic activity and a sharp decrease in RNP particles. The results obtained make it possible to consider the hyperchromic neuron as a cell with a diminished functional activity. PMID- 2930974 TI - [Errors in blood transfusion. Causes and prevention]. AB - Authors, analyzed the possible sources of errors resulting in the administration of incompatible blood and of the specific professional responsibilities connected to that error, point out the precautions to minimize it and the therapy which is to be followed in the cases of serious haemolytic transfusion reactions. PMID- 2930975 TI - [Use of oral bacteria therapy in childhood during acute enteritis and functional chronic diarrhea. Clinical experience]. AB - There are some theoretical reasons to give an oral bacterial therapy when intestinal ecosystem changes its composition. The authors would verify the clinical effectiveness or oral bacterial therapy during acute and functional chronic diarrhea: even if the course of the illness doesn't become shorter, oral bacterial therapy moreover may be useful in reducing the risk of having casual carries of pathogenic agents and may restore an intestinal ecosystem previously modified by antibiotic therapy. PMID- 2930976 TI - [Effect of blood levels of carboxyhemoglobin (COHb) on erythrocyte filtration time in young smokers]. AB - The effects of chronic exposure to carbon monoxide on some rheologic parameters (erythrocyte filtration time in particular) and on FEV1, and on FEF25-50 were studied in young smokers. A positive correlation among number of cigarettes day, COHb blood levels and erythrocyte filtration time was found. Packed red cell volume, fibrinogen concentration and platelet count were unaffected; no evidence of small-airway obstruction was observed. The alteration of erythrocyte deformability may be an early sign of hemorheological impairment which can progressively worse if high COHb blood levels are chronically maintained, with damaging effects on vessel function. PMID- 2930977 TI - [Frontal and naso-mental island flaps in partial loss of nasal substance- advantages and disadvantages]. AB - The authors illustrate the frontal and naso-labial island flaps for reconstruction of loss of substance of the nose, comparing them with the more usual rotation flaps and discussing their advantages and disadvantages. Regarding the advantages: the satisfactory aesthetic result immediately after the operation, the oncological excision and the complete reconstruction in only one surgical step, the valid vascular support with sure vitality of the flap and the elegance of the surgical technique. Among the disadvantages: the limited rotation arc, the excessive bulk of the frontal flap for the reconstruction of the internal canthus, the frequent "trap door" effect, the possible relief in the area of the subcutaneous tunnel and the more laborius surgical intervention. PMID- 2930978 TI - [Isoflurane: clinical experience in plastic surgery]. AB - The authors' experience with Isoflurane, a volatile anesthetic agent recently introduced in Italy, is reported. A non-selected group of twenty patients, who underwent plastic surgery operations, represents the subject of this study. It is concluded that the clinical properties of Isoflurance are fully satisfactory with respect to the anesthestiological needs of plastic surgery. PMID- 2930979 TI - [Epidermoid cysts of the testis: conservative treatment?]. AB - The epidermoid cyst of the testis is a monolayer teratoma with no malignant character, when pure. Therefore, its recognition on the basis of macroscopic and freeze histologic grounds should allow a conservative surgical removal, with saving of the testis. Out of the more or less 150 reported cases, about 85% have been treated by orchiectomy, about 15% by either enucleation or partial orchiectomy. In no case except one, a more thorough histologic examination of the removed cyst, malignant structures have been observed. In no case, with a follow up from a few months to more than 15 years, a recurrence occurred. Two cases are presented and discussed, in which a conservative choice was made and clinical follow-up carried out. PMID- 2930980 TI - [Blood filtration for the prevention of microaggregate damage: various critical aspects]. AB - Recent studies shown that patients receiving more than 20% of their total blood volume through 170 mu standard blood filters, may occur in severe organic damage such as pulmonary, cerebral, renal embolism due to microaggregates contained in stored blood. Microaggregate size varies from 10-200 mu; they are composed of platelets, leucocytes, red cells debris and fibrin strands, which take form few hours after blood storage begins and whose number progressively increases. In this study we analyzed microaggregate composition, factors causing their formation, side effects due to massive transfusion and blood filtration techniques capable to prevent a direct blood infusion. There is a variety of available filters, but screen filters seem to offer more important and practical advantages than depth filters do. The use fine pore filters is recommended when more than three blood units are to be infused during only one administration. PMID- 2930981 TI - [Echographic diagnosis of gestational age and law 194]. AB - The authors examine the various biometrics parameters evidentiable at the 13th week of pregnancy, which is so important age for the limits imposed by the law 194, that regulates the legal abortion. These findings are studied as for their evidentiability and their diagnostic predictivity aiming to single out the most reliable. As for the results obtained examining the singular parameters, the authors conclude that the goal of the echographist is to search for the fetal CRL and BPD: they are characterised of an optimum predictivity and a good evidentiability, besides they provide direct data about the embryo dimensions. If these measurements are not evidentiable the operator can base his diagnosis on the other parameters that do not refer directly to the embryo. At last the authors sustain that who carried out the ultrasound examination should not "force" the diagnosis trying to establish the gestational age with excessive exactness; on the contrary he must limit himself to provide the evidentiable biometric values, indicating the minimum and the maximum age that is compatible with them. It is up to the physician who performs the termination of pregnancy to draw the correlations about the gestational age. PMID- 2930982 TI - [Indications for diagnostic and surgical digestive endoscopy in childhood: personal clinical experience]. AB - From January 1983 to December 1984 in the Division of Pediatric Surgery of Parma, 112 endoscopies of upper gastro-intestinal tract (UGT) were done. Besides the authors refer 49 endoscopies of the colon. Endoscopic indications of the UGT included evaluation of the esophagus in gastro-esophageal reflux, achalasia, lye ingestion, gastro-duodenal ulcer, bleedings of UGT, removal of foreign bodies. The indication of the colonoscopy included bleedings and all symptoms of colitis. The endoscopic procedures were done under sedation or in general anesthesia. PMID- 2930983 TI - [Baseball during the growing years: repercussions on the cardiovascular system (echocardiographic evaluation)]. AB - The influence upon the cardiovascular system of a period (21 months) of physical training program for baseball was studied in 40 normal children (aged 8 to 10 years) in an experimental (20) and control (20) group. The echocardiographic changes observed at the end of the period proved to be substantially alike in both groups. The physiopathological involvements linked to the baseball training in the prepubescent age are discussed. PMID- 2930984 TI - [Our experience with the diagnostic and prognostic unreliability of pre- and postoperative CEA in human breast cancer]. AB - The carcinoembryonic antigen (CEA) levels were determined in 42 breast cancer patients at I, II, III, IV stages of TNM classification. Plasmatic preoperative CEA levels was under 6 ng/ml in the 94% of patients. The postoperative CEA levels of six patients who developed metastases during the follow-up was elevated in five cases, but the elevation never preceded the clinical and radiological diagnosis of metastases. PMID- 2930985 TI - [Analysis of a case series of 1,500 suicide attempts in Parma (1971-1983)]. AB - The authors analyse data from a case series of 1500 attempted suicides, gathered by the University of Parma, Institute of Psychiatry. The attempted suicides were studied according to sex, age, class, place where the subject was born and where the attempt took place, marital status, family background, level of education, financial position, occupation, as well as the method of the attempted suicide and the mental condition of the patient when under observation. The main points to emerge were the similarities between these data and those of the literature, as well as the psychological features and social background of these patients. Our study also confirms the results of a previous research on 500 attempted suicides, here included: the obtained out of the last 1.000 cases confirms those out of previous 500. PMID- 2930986 TI - Late rupture of knitted Dacron double velour arterial prostheses. Report on four cases. AB - Late fibre breakage with longitudinal tears occurred in 4 patients of a series of some 300 implanted knitted Dacron double velour arterial prostheses. The four patients all received their grafts for occlusive aortoiliac disease in the year 1978, and the rupture was found 4 to 6 years later. Three of the failures occurred in axillo-bifemoral bypass grafts, whereas the fourth patient had a bifurcated aortic prosthesis. Dilatation was significant in the latter graft only. Structural weakness might appear during production, during later handling, or possibly as a result of interference from infected material or host factors. The cause of graft failures in the present series could not be ascertained. Whatever type of knitted Dacron used, a 2-3% incidence of graft deterioration might be expected. Therefore regular, life-long follow-up of patients with Dacron arterial prostheses seems warranted. PMID- 2930987 TI - Cyproterone acetate as initial treatment and maintenance therapy for hirsutism. AB - Thirty-four patients with hirsutism were treated for 9 months with 100 mg cyproterone acetate (CA) given on days 5-15 of the menstrual cycle together with a combination oral contraceptive containing 2 mg CA and 50 micrograms ethinyloestradiol (Diane) given on days 5-25 of the cycle. After 9 months treatment patients were randomised to a 12 month double-blind cross-over trial comparing Diane plus 25 mg CA with Diane plus placebo, to test the efficacy of low-dose CA as maintenance therapy. Thirty-one patients (92%) experienced moderate or good subjective improvement in hirsutism on high-dose CA, associated with a 40% mean overall improvement in objective hirsutism grade and 13% overall reduction in hair growth rate measured by a photographic technique. Minor or moderate side effects were experienced by 64% of patients and severe side effects by 11% at this dosage. There was a mean subjective relapse rate of 33% when patients were changed to low dose CA, and relapse rates were not significantly different between the two regimens with 28% relapsing on 25 mg CA + Diane and 48% on placebo and Diane (P less than 0.05). Despite significant subjective relapse with low-dose treatment there was no significant deterioration in objective hirsutism grade or hair growth rate determined photographically. Levels of plasma testosterone, sex hormone binding globulin, free testosterone (derived) and androstenedione fell significantly on high dose CA and this reduction was maintained during low dose therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2930990 TI - [Influence of lymphocyte chalone on normal human lymphocytes and malignant cells]. PMID- 2930988 TI - Interactions of an anti-androgen (cyproterone acetate) with the androgen receptor system and its biological action in the rat ventral prostate. AB - Male Wistar rats were castrated and implantated with testosterone-filled silastic depots (in vitro release rate: 60 micrograms/24 h) prior to treatment with 10 mg cyproterone acetate (CyAc) on day 1, and 5 mg on days 4, 7, 10 and 13. Animals were sacrificed on day 14. Control animals were treated identically, with the exception of CyAc administration. Blood was collected and the ventral prostates of 6-8 animals were pooled, homogenized and processed into cytosol and purified nuclei. Steroid determinations (CyAc, testosterone, 5 alpha-dihydrotestosterone (DHT), 5 alpha-androstane-3 alpha,17 beta-diol (3 alpha-diol)) were performed by RIA. Specifically bound DHT (charcoal resistant DHT = CR-DHT) represents DHT values (RIA) following treatment of cytosol or nuclear extract with dextran coated charcoal. The androgen receptor was determined in cytosol and nuclear extract by 'exchange assay' using [3H]methyltrienolone (MT) (18 h, 15 degrees C). The main results were: 1) The steroid levels in plasma (testosterone, DHT, 3 alpha-diol) were in the range of untreated adult animals and not significantly influenced by the CyAc treatment. Final CyAc levels were 305 +/- 58 nmol/l (mean +/- SD, n = 5).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2930989 TI - The clinical features and incidence of concurrent intra and extra uterine pregnancies. AB - Concurrent intra and extrauterine pregnancies have always been thought to be rare with a mean annual incidence of 1:30.000. The condition has been reported more frequently in the recent literature. If the incidence is increasing it is a serious development as the condition is often undiagnosed. The paper describes 5 patients with the condition presenting between 1976-1981 an incidence of 1:4000 deliveries. In two of these five patients the intrauterine pregnancy was diagnosed first and the ectopic pregnancy was undiagnosed until much later. The presence of intrauterine pregnancy often leads us to ignore the possibility of a concurrent extrauterine pregnancy. Considering that ectopic pregnancy may still cause maternal death, we believe that the condition has to be considered more often. Certain features may suggest the diagnosis. 1) Lack of vaginal bleeding or uterus larger than 9 week size with a proven ectopic pregnancy. 2) Presence of two corpora lutea at laparoscopy. 3) Ultrasound to diagnose an adnexal mass. 4) Failure of serum hCG to return to normal after abortion. The text also discusses the natural history of the condition and the higher incidence expected in the future with the wider use of ovulation inducing agents. PMID- 2930991 TI - Detection of human lymphocyte subpopulations by using monoclonal antibodies and protein A-coated erythrocytes. AB - The results obtained by using the protein A-rosette assay for human peripheral blood lymphocytes treated with a series of monoclonal antibodies were very close to the estimates obtained by indirect fluorescence. The percentages of T3-, T4-, T8- and DR-positive cells (T3 = T lymphocytes, T4 = helper T lymphocytes, T8 = suppressor T lymphocytes, DR = B, L and null cells) in normal and pathological peripheral blood were found to vary within the limits reported by many other authors using different techniques for the identification of cells binding the specific monoclonal antibody. PMID- 2930992 TI - Intravenous monoclonal antibody (BT 5/9) for the treatment of acute graft-versus host disease. PMID- 2930993 TI - Transient ischaemia of the proximal femoral epiphysis in the child. Interpretation of bone scintimetry for diagnosis in hip pain. AB - 99mTc-MDP-scintimetry was performed in 25 consecutive cases of radiographically silent transient synovitis of the hip in children. Fourteen cases had normal scintimetry; seven cases had an increased uptake in the epiphysis; four cases had markedly defective uptake in the epiphysis, indicating interrupted vascular supply. At repeat scintimetry 6 weeks later, the uptake was normal or increased in three of these four cases; the one case with a persistent defect was the only case in this series who later developed radiographic evidence of Legg-Calve Perthes' disease. In some cases presenting with clinical symptoms of synovitis of the hip, there is a transient, spontaneously recovering ischaemia of the proximal femoral epiphysis, not followed by radiographic evidence of necrosis. This should be considered in attempts to make a pre-radiographic diagnosis of Legg-Calve Perthes' disease by radionuclide methods. PMID- 2930994 TI - Synthesis and spectroscopic characterization of pyridyl N-oxidized zimeldine metabolites. PMID- 2930995 TI - Synthetic inhibitors of alcohol dehydrogenase. Pyrazoles containing polar groups directly attached to the pyrazole ring in the 4-position. PMID- 2930996 TI - Hormone changes and beta-endorphin in the pathogenesis of hemorrhagic shock. AB - Plasma levels of some hormones, implicated in the pathogenesis of hypovolemic shock (ACTH, corticosterone, plasma renin activity, aldosterone, prostaglandins, vasopressin and beta-endorphin) were examined on rats with hemorrhagic shock. The animals were treated with the specific opioid antagonist, naloxone (1 mg/kg body weight, i. v.). The results demonstrated that during the first, compensated stage of hypovolemic shock, an increase of ACTH, corticosterone, vasopressin, and stimulation of renin-angiotensin-aldosterone system was evident, that is, an activation of hormonal mechanisms responsible for blood pressure and blood volume restoration occurred. beta-Endorphin and prostaglandin E-release during hemorrhagic shock might contribute to the cardiodepressor changes. Naloxone treatment prevented the development of shock into a progressive stage by several eventual mechanisms: An antagonism of opiate receptors. Stimulation of ACTH secretion, followed by an increased secretion of glucocorticoids or a direct effect on adrenocortical function. Stimulation of aldosterone secretion by ACTH or directly. PMID- 2930997 TI - Mechanism of action of beta-endorphin and naloxone in hypophysectomized rats with hemorrhagic shock--the role of CNS. AB - The studies were performed on hypophysectomized rats with hemorrhagic shock treated intracerebroventricularly (i. c. v.) or intravenously (i. v.) by naloxone. The purpose of the investigation was to elucidate whether pituitary beta-endorphin (beta E) contribute to the hypotension and cardiodepressor changes during hypovolemic shock, the role of CNS opioid receptors for these effects, and the mechanism of action of naloxone. The results showed: The cardiorespiratory and hormonal changes in hypophysectomized rats represent an excellent model for the evaluation of the effects of some hormones, blockers or inhibitors, after either i. c. v. or i. v. administration. Neither i. c. v. nor i. v. administration of naloxone on hypophysectomized rats prevented the cardiodepressor changes during hemorrhagic shock. The beneficial effect of naloxone in hemorrhagic shock, manifested only on animals with intact pituitary glands, suggested that its therapeutic effect is mediated by CNS opioid receptors, and pituitary beta E may potentiate the hypotension during hypovolemic shock through an action on opiate receptors in the CNS. In hypophysectomized rats naloxone did not stimulate aldosterone secretion as it did in non hypophysectomized rats with hemorrhagic shock, which indicated that this effect is secondary, accomplished by stimulation of the secretion of both ACTH and beta E. PMID- 2930998 TI - Double-blind comparison between a serotonin and a noradrenaline reuptake blocker in the treatment of depressed outpatients. Clinical aspects. AB - Seventy-five outpatients with major depressive disorder (RDC) were randomly referred to treatment with a dominant serotonin (5-HT) uptake inhibiting drug (zimeldine, 100 mg b.i.d.) or a dominant noradrenaline (NA) uptake inhibiting drug, (maprotiline, 75 mg b.i.d.). The total antidepressive effect was similar in the two groups for up to 4 weeks of treatment. Both drugs gave an effect on the depressive syndrome as a whole, with no preference for mood, anxiety, retardation or vital symptoms. Good response to the NA drug correlated to few prior episodes and few years since first episode, whereas the 5-HT drug had its best effect when there were several previous episodes. PMID- 2930999 TI - Plasminogen activators, tissue degradation, and cancer. PMID- 2931000 TI - A unified theory for the mechanism of the lethal hit by cytotoxic T lymphocytes (CTL) and natural killer (NK) cells as defined by antisera capable of blocking the lethal hit stage of cytotoxicity. PMID- 2931001 TI - Requirement for Lyt-2/3 molecules on allospecific cytolytic T lymphocyte clones is dependent upon target cell antigen density. PMID- 2931002 TI - The role of the T3 molecular complex on human T lymphocyte-mediated cytotoxicity. AB - The above overview of the experimental data clearly indicates that the T3 molecular complex is intimately involved in T cell activation. The precise role of the T3 complex in the activation process, however, is not clearly understood. The surface association of the T3 complex with the antigen receptor, along with the ability of antibodies to these molecules to render T cells receptive to IL2, reveal a possible mechanism by which specific antigen initiates T cell activation and growth. However, it would be difficult to reconcile this specific effect of anti-T3 antibodies with their effect on CTL function. Since the T3 complex is not a specific marker of any particular effector T cell population, but it is found on all T lymphocytes, we favor the hypothesis that the complex is involved in a more fundamental step of T cell activation, and we believe that triggering of the 'lethal hit', expression of IL2 receptors, and secretion of IL2 are mere manifestations of this basic process. The natural ligand of the antigen receptor is obviously the specific antigen. However, the natural ligand of the T3 complex is unknown. Possibly, its natural ligand is the antigen receptor itself after it has interacted with antigen. A simple scenario, then of the early events of T cell activation would include antigen recognition and binding, followed by an interaction between the antigen receptor and the T3 complex which then activates or allows expression of specific pathways depending on the particular effector population involved. Thus, the inhibition of CTL function by anti-T3 antibodies could be explained by interference with the antigen receptor-T3 complex interaction following target cell recognition. This interaction may be the event that signals the initiation of the 'lethal hit' process. PMID- 2931003 TI - p215 and p24: two membrane-associated proteins expressed on cloned cytolytic T cells but not on cloned helper T-cells. AB - Cloned lines of murine alloreactive cytolytic and helper T cells were derived from secondary mixed leukocyte cultures. Cells from three TC lines and four TH lines were internally labeled with 35S-methionine and then disrupted by hypotonic lysis. Low density (plasma membrane-enriched) and high density (endoplasmic reticulum-enriched) membrane fractions were isolated from each cloned cell line and analyzed by SDS-PAGE under reducing conditions. Two proteins were identified which were associated with membrane fractions from each of the TC lines but none of the TH lines. One of these, p215, migrated as a broad band with an apparent molecular weight of 200-220 kD. The other, p24, migrated as a sharp band or closely spaced doublet with an apparent molecular weight of 24 kD. Immunoprecipitation studies using monoclonal antibodies to T200, LFA-1, Thy 1, and Lyt 2 revealed that p215 was a variant of T200 found on TC lines but not on TH lines. Treatment of solubilized membrane proteins from TH lines with anti-T200 precipitated a 180-195 kD protein band seen on each of the TH lines but none of the TC. In contrast, p24 was not precipitated by any of these monoclonal antibodies. It appears that p24 represents a previously unidentified protein which is unique to TC and thus deserving of further study as to its functional significance. PMID- 2931004 TI - Destructive interactions between murine macrophages, tumor cells, and antibodies of the IgG2a isotype. PMID- 2931005 TI - Psychosomatic aspects of movement disorders. PMID- 2931006 TI - Behavioural psychotherapy for neurological illness. PMID- 2931007 TI - Ageing and lung function. AB - Studies of lung function have largely ignored the elderly. This paper reviews what is known of the decline in measurements of lung function, and focuses on reduced elastic recoil as a key to these changes. Independent anthropometric changes which may affect lung function with advancing years are also discussed. PMID- 2931008 TI - Urinary incontinence in the disabled elderly male. AB - A combined approach between Departments of Urology and Geriatric Medicine to the diagnosis and management of urinary incontinence in disabled elderly men with neurological lesions where outflow obstruction is thought to be a contributory factor is described. After a dual out-patient assessment, patients have a planned admission to a geriatric ward where urodynamic studies and cystoscopy are performed, followed, where necessary, by appropriate surgery. The results in 75 patients are presented. Single urodynamic studies alone are effective in establishing the diagnosis in only 20% of cases. The largest group needing surgical treatment are those with combined cerebrovascular disease and prostatic enlargement. The degree of disability, but not age, influences the outcome of surgery in such cases. The benefits of collaboration to such patients and to the departments are discussed. PMID- 2931009 TI - Ultrastructure of the cysts of Sarcocystis tarandivulpes from skeletal muscle of reindeer (Rangifer tarandus tarandus). PMID- 2931011 TI - Accident and violation rate of handicapped drivers. PMID- 2931010 TI - Mechanism of suppression of the depressed lymphocyte response in lung cancer patients. AB - We studied the function of monocyte-mediated suppression in the proliferative responses of depressed T-cells of patients with advanced lung cancer, with both local (Stage III) and extrapulmonary metastasis (Stage IV). The mononuclear cells of 13 non-treated patients showed a significant drop in proliferation upon stimulation with suboptimum, optimum and supraoptimum doses with regards to normal controls (p less than 0.001). On treating T-cells with indomethacin, lymphoblastic transformation increased in both groups (patients and controls), but was significantly greater in the patient group (p less than 0.001). The lipopolysaccharide (LPS) exerted an inhibitory effect on the suppressor cells of normal individuals, yet failed to do so in the case of patients treated either with or without indomethacin. The stimulation of the patients mononuclear cells with PWM failed to increase proliferation, and was not affected by either indomethacin of LPS. Our conclusions are as follows: Patients with lung cancer present a drop in mononuclear cell proliferation when stimulated with PHA; This phenomenon may be due to an exacerbation of the immune systems suppressor function; One of the suppressor mechanisms is prostaglandin-dependent and mediated by monocytes; The B-cells have no relevant functions. PMID- 2931012 TI - Life adaptation after percutaneous transluminal coronary angioplasty and coronary artery bypass grafting. AB - Life adaptation of 32 patients who had undergone percutaneous transluminal coronary angioplasty (PTCA) for coronary stenosis was compared with that of 15 patients who had coronary artery bypass grafting (CABG). Patients were matched for psychosocial, anatomic and cardiac functions. Life adaptation was measured at 6 and 15 months after PTCA or CABG by the Psychosocial Adjustment to Illness Scale (PAIS), a multidimensional instrument that evaluates change in 7 primary life domains. The overall PAIS scores for patients who had undergone PTCA were significantly better (p less than 0.04) than the scores for those who had undergone CABG after 6 months, and this superior functioning continued after 15 months (p less than 0.05). After 6 months patients who had undergone PTCA functioned better at work (p less than 0.005), in sexual performance (p less than 0.0001) and with their families (p less than 0.002). The improvement in work functioning continued at 15 months (p less than 0.04), but the differences in sexual and family domains became nonsignificant. PMID- 2931013 TI - Percutaneous transluminal coronary angioplasty after previous coronary artery bypass surgery. AB - To improve symptomatic status and avoid repeat coronary artery bypass graft surgery (CABG), 115 lesions were approached for transluminal coronary angioplasty (PTCA) in 94 patients (82 men, 12 women) with angina pectoris and prior CABG at a mean of 60 months (range 4 to 192) after CABG. Fifteen patients were in Canadian Cardiovascular Society functional class I, 32 were in class II, 31 were in class III, and 16 were in class IV. Patients were 37 to 76 years old (mean 57). PTCA was successful (at least a 40% reduction in stenosis diameter and improvement in symptomatic status) in 83 patients (88%) and 103 (90%) lesions. Mean stenosis was reduced from 80 +/- 14% to 20 +/- 16% (mean +/- standard deviation) and mean pressure gradient from 41 +/- 7 mm Hg to 14 +/- 6 mm Hg. Seven patients had lesions that could not be crossed for technical reasons and these patients underwent non-emergency CABG. Four patients required emergency CABG after PTCA; 1 patient subsequently died and 2 survived acute myocardial infarction. One patient had a femoral artery laceration, which required surgical repair. At a mean follow up of 8 +/- 4 months, 63 patients (76%) with initially successful results were free of angina or in improved condition. Of the remaining 20 patients, 18 consented to repeat coronary angiography. Four patients did not have restenosis. Of the 14 patients with documented restenosis, 5 underwent successful repeat PTCA, 5 had repeat CABG, and 4 were treated medically. Thus, when coronary anatomy is suitable, PTCA is an effective alternative to reoperation in symptomatic patients with prior CABG. PMID- 2931014 TI - Effect of diltiazem and ibuprofen on right ventricular hypertrophy in an experimental model of hypoxic pulmonary hypertension. AB - The effectiveness of diltiazem, a slow channel calcium blocker, ibuprofen, a nonselective inhibitor of prostanoid synthesis, and the selective inhibition of thromboxane A2 with imidazole and UK-38,485 in retarding the development of right ventricular (RV) hypertrophy was assessed in a rat model of chronic hypoxic pulmonary hypertension. Both ibuprofen and diltiazem significantly reduced RV hypertrophy in the chronically hypoxic rat. In contrast, selective inhibition of thromboxane A2 was ineffective in reducing RV hypertrophy. The beneficial effect of ibuprofen was unrelated to inhibition of thromboxane A2. Furthermore, thromboxane A2 did not appear to be involved in the development of RV hypertrophy in this experimental model of hypoxic pulmonary hypertension. PMID- 2931015 TI - Cardiorespiratory response to exercise in Ebstein's anomaly. AB - Fourteen patients with unrepaired Ebstein's anomaly underwent maximal exercise testing between October 1982 and April 1984. Compared with control subjects, these patients had significantly lower values for total work performed, exercise time, maximal oxygen uptake, blood oxygen saturation at rest and during exercise, and heart rate and systolic blood pressure during maximal exercise. They had a significant increase in heart rate at rest. The ventilatory equivalent for oxygen was increased significantly both at rest and during exercise. Thus, patients with Ebstein's anomaly have decreased exercise tolerance owing to both cardiac and respiratory limitations. PMID- 2931016 TI - Results of balloon valvuloplasty in the treatment of congenital valvar pulmonary stenosis in children. AB - Transluminal balloon valvuloplasty was used in the treatment of congenital valvar pulmonary stenosis in 19 children, aged 5 months to 18 years. The right ventricular (RV) systolic pressure and RV outflow tract gradient decreased significantly immediately after the procedure (95 +/- 29 vs 59 +/- 14 mm Hg, p less than 0.01, and 78 +/- 27 vs 38 +/- 13 mm Hg, p less than 0.01). Seven of these patients were evaluated at cardiac catheterization 1 year after balloon valvuloplasty. No significant change occurred in RV systolic pressure or RV outflow tract gradient at follow-up evaluation compared with measurements immediately after balloon valvuloplasty (60 +/- 5 mm Hg vs 56 +/- 12 mm Hg and 39 +/- 5 vs 38 +/- 10 mm Hg). In addition, follow-up evaluation was performed using noninvasive methods and included electrocardiography (n = 13), vectorcardiography (n = 11) and Doppler echocardiography (n = 11) Doppler echocardiography in 11 patients 15 +/- 9 months after balloon valvuloplasty showed a continued beneficial effect with a mild further decrease in RV outflow tract gradient. Thus, balloon valvuloplasty is effective in the relief of pulmonary stenosis. PMID- 2931017 TI - Cardiac care for children with Down's syndrome. PMID- 2931018 TI - Laparoscopic findings in seven patients with nodular regenerative hyperplasia of the liver. AB - We describe the laparoscopic findings in seven patients with nodular regenerative hyperplasia of the liver. This unusual condition is characterized by nodules of hyperplastic hepatocytes diffusely distributed throughout the liver parenchyma, without fibrous septa between the nodules. In all patients, the diagnosis was made by liver biopsy under laparoscopic control. Laparoscopy revealed the presence of portal hypertension, nonnodular undulated liver surface, recognizable lobular pattern, and a hepatic consistency softer than normal to palpation. All of these findings indicated a diagnosis of nodular regenerative hyperplasia. Definitive diagnosis was established from biopsy specimens. PMID- 2931019 TI - Cutaneous manifestations of intravenous vasopressin therapy. AB - A 79-year-old woman with primary biliary cirrhosis was admitted with esophageal variceal hemorrhage. She was initially managed with sclerosing of esophageal varices with no relief from the bleeding. Intravenous Vasopressin was started, but had to be discontinued because of cutaneous changes. A portocaval shunt was performed to control the variceal bleeding. Postoperatively she did poorly from sepsis and hepatic encephalopathy and died 46 days after admission to the hospital. PMID- 2931020 TI - Laser therapy--things to come: multiple spectra and photodynamic therapy. AB - The clinical application of endoscopic laser therapy has expanded recently to include the resolution of various strictures of the gastrointestinal tract and the fracture of gallstones. These uses and the growing utilization of photodynamic therapy of tumors in conjunction with hematoporphyrin derivative is reviewed. These advances hold enough therapeutic promise to demand careful consideration. PMID- 2931021 TI - Abnormal immunoregulation in remission Hodgkin disease. AB - Peripheral blood mononuclear cells from 11 patients with remission Hodgkin disease and 20 normal controls were incubated with irradiated allogeneic lymphocytes in one-way mixed lymphocyte cultures. Simultaneously, modified assays were performed by adding supplemental irradiated PBM, T lymphocytes, or adherent cells autologous to the responders. Baseline allogeneic responsiveness of patients and controls was not different. However, significant suppression (p less than .01) was demonstrated when the cultures were supplemented with patient mononuclear cells or adherent cells, an effect not found with similar supplemental cells from controls. Conversely, T-cell supplementation of control cultures produced more than twofold increases in proliferation but significantly less augmentation in the patients' cultures (p less than .01). T-cell subset analysis in six patients showed decreased helper: suppressor cell ratios. Hodgkin disease patients have adherent suppressor cells, which persist during remission, as well as a defect in T-cell helper function. PMID- 2931022 TI - Severe hypertension induced by naloxone. AB - To evaluate the role of endogenous opioid peptides in regulating the blood pressure of hypertensive individuals, we administered the opiate antagonist, naloxone. One individual developed a severe hypertensive response, mean arterial pressure rising from a baseline of 107 mmHg to 147 mmHg 145 min after naloxone injection and infusion. After stopping naloxone, his blood pressure rapidly returned to baseline. Re-challenge with naloxone and clonidine resulted in a modest reduction of blood pressure in contrast to the profound hypotension induced by clonidine alone during a third session. Thus, endogenous opioids appear to regulate blood pressure in some hypertensive patients and opiate antagonists must be administered with caution to these individuals. PMID- 2931023 TI - Sonographic diagnosis of Down syndrome in the second trimester. AB - We report a sonographic sign consisting of increased skin or soft tissue thickening at the back of the fetal neck during the second trimester, which correlates well with the diagnosis of Down syndrome. Eight hundred consecutive sonograms were performed in conjunction with genetic amniocentesis where four fetuses had trisomy 21 (Down syndrome) by karyotype. Two or 50% had sonographic findings consistent with Down syndrome. Recently we described a retrospective series where 904 sonograms were performed at the time of amniocentesis and seven fetuses had trisomy 21 on cytogenetic analysis. The abnormal sonographic finding at the back of the neck was present in three of those seven cases. Combining these series, 1704 fetuses were examined and 11 cases of Down syndrome were diagnosed cytogenetically. Five of the 11 or 45% had an abnormal sonogram suggestive of Down syndrome. Two of these were patients undergoing sonography for ascertainment of dates at 16 weeks and submitted to amniocentesis solely on the basis of this sonographic finding. PMID- 2931024 TI - The effect of serotonergic blockade in postpartum preeclamptic patients. AB - Thirty postpartum preeclamptic patients from the University of South Florida Obstetrical Service were enrolled in a placebo-controlled, randomized, double blind study to test the effectiveness of ketanserin in lowering the blood pressure. An intravenous bolus of ketanserin resulted in a significant drop in the mean arterial blood pressure. The decrease in the blood pressure could be maintained by a continuous infusion of ketanserin. Hypertension returned after the medication was discontinued. These observations suggest that ketanserin, a selective blocker of type II serotonin receptors, may be effective in acutely reducing elevated postpartum blood pressure in preeclamptic patients, and that serotonin may play a role in the pathogenesis of preeclampsia, but not be important as a mediator in the severity of the disease. PMID- 2931026 TI - Reconstructive pelvic operations for in vitro fertilization. AB - Lysis of adhesions, bilateral salpingectomy, and ovarian suspension were carried out in 54 normal ovulatory patients with long-standing infertility that was associated with severe pelvic adhesions after multiple laparotomies for reimplantation of the fallopian tubes, salpingostomy, lysis of adhesions, or severe endometriosis. Ovulation was induced in 39 patients after laparotomy for in vitro fertilization, with the use of human menopausal gonadotropin, pure follicle-stimulating hormone, and human chorionic gonadotropin. Oocyte retrieval by laparoscopy was accomplished in 37 patients, and embryo transfer was carried out in 36. Pregnancy after in vitro fertilization and embryo transfer occurred in 14 patients. Although severe adhesions recurred in four patients, a significant improvement was obtained after the procedure in the others. PMID- 2931025 TI - Abdominal sacral colpopexy with Mersilene mesh in the retroperitoneal position in the management of posthysterectomy vaginal vault prolapse and enterocele. AB - During a 12-year study period from 1972 to 1984, 56 patients underwent abdominal sacral colpopexy with retroperitoneal interposition of a suspensory hammock between a prolapsed vaginal vault and the anterior surface of the sacrum. They were followed from 6 months to 12 1/2 years, and constitute the basis of this report. In most patients, a synthetic mesh was the material interposed. Hysterectomy had previously been performed on 53 patients, and in two patients there was congenital absence of the uterus. Indications for abdominal sacral colpopexy, surgical technique, complications, and results of operation are discussed. Seven additional patients underwent this operation after termination of the defined study period. PMID- 2931027 TI - Reliability of gynecologic sonographic diagnosis, 1978-1984. AB - The indications for gynecologic ultrasonography, as well as the reliability of sonographic diagnoses in gynecologic patients, remain controversial. In an effort to evaluate the reliability of the gynecologic sonographic diagnoses rendered at this institution, we analyzed 900 patients available for follow-up. The referral diagnosis was confirmed in 331 patients (36.8%). In 531 patients (59%), sonography established the diagnosis. Thirty-eight (4.2%) of the diagnoses rendered did not reveal the actual status of the patient and were deemed to be "misleading." Twenty-one of the misleading diagnoses involved the attempted diagnosis of pregnancy at less than 5 weeks' menstrual age. Sonography correctly identified 353 of 370 patients with normal pelvic anatomy. Specific clinical settings in which gynecologic sonography could be beneficial are presented. PMID- 2931029 TI - Passive calcium-buffering capacity of a rabbit ventricular homogenate preparation. AB - This study characterizes the passive Ca2+-binding capacity of a crude homogenate fraction prepared from rabbit ventricular tissue. The soluble and particulate fractions of the homogenate were separated by centrifugation, and the Ca2+ binding capacity of each fraction was measured separately with Ca2+-selective electrodes and then summed to obtain the Ca2+-binding capacity of the total tissue homogenate. Qualitatively, the Ca2+ bound to the homogenate exhibited both relatively high- (Km less than 1 microM) and low-affinity (Km greater than 10 microM) sites over the physiological range of free Ca2+ concentrations. The total homogenate bound 72, 128, and 308 mumol Ca2+/kg wet wt tissue at 1, 10, and 50 microM free Ca2+ concentrations, respectively. The Ca2+ bound to the homogenate was mostly La3+ displaceable, which suggests that it represents a largely noncompartmentalized, rapidly exchangeable fraction of Ca2+. Myofibrillar ATPase activity was examined as a function of free Ca2+ concentration in an ionic medium similar to that used in the Ca2+-binding experiments. At free Ca2+ concentrations that stimulated myofibrillar ATPase activity half maximally, the measured rise in Ca2+ bound to the homogenate above resting values was greater than 100 mumol/kg wet wt. These data provide base-line values for the passive Ca2+-buffering capacity of the myocardium, although relevance to the physiological setting must be interpreted with caution. PMID- 2931030 TI - Evidence for protein kinase C as a regulator of intestinal electrolyte transport. AB - We examined the possibility that the Ca2+-and phospholipid-dependent protein kinase, protein kinase C, may regulate intestinal electrolyte transport. By use of two active phorbol esters, known activators of protein kinase C, we studied the secretory response in rat small intestine. In the in vivo enteropooling assay, 4 beta-phorbol 12-myristate 13-acetate given by gavage produced intestinal fluid secretion and accumulation comparable with that of known secretagogues. The response was dose dependent and only partially blunted at higher doses by atropine. Known inactive phorbol esters failed to elicit a secretory response. In Ussing chamber preparations, 4 beta-phorbol 12,13-dibutyrate applied on the serosal side produced a dose-dependent increase in short-circuit current (Isc). This response was totally dependent on the presence of Cl ion, and as seen in vivo atropine only partially attenuated the Isc response to high concentrations of phorbol ester. Only a minimal increase in Isc was observed when the ester was applied to the mucosal side. Protein kinase C was found to phosphorylate the microvillus membrane of the enterocyte, and the phosphorylation was stimulated by phorbol ester in a concentration-dependent manner. Two membrane proteins of Mr 51,000 and 46,000 were the primary substrates of the enzyme. These studies demonstrate that phorbol esters, specific activators of protein kinase C, elicit the secretory response in rat small intestine both in vivo and in vitro and that this response is mediated by an increase in Cl ion secretion. Furthermore, protein kinase C-mediated phosphorylation of specific microvillus membrane proteins suggests that protein kinase C may modify the functional state of the microvillus membrane of the enterocyte. PMID- 2931028 TI - SIg-E- ("null-cell") non-Hodgkin's lymphomas. Multiparametric determination of their B- or T-cell lineage. AB - The authors performed immunophenotypic, functional, and molecular analysis of the neoplastic cells from 20 cases of SIg-, E-("null-cell") non-Hodgkin's lymphoma (NHL) in order to determine their lineage, better define this category of NHL, and evaluate the lineage specificity of selected phenotypic markers and the individual and collective utility of these approaches. They assigned 4 cases to the T-cell lineage, and 15 cases to the B-cell lineage, and 1 case remained indeterminant on the basis of immunophenotypic analysis. The cells from 2 cases assigned to the T-cell lineage expressed unusual phenotypes, but their T-cell derivation was confirmed by the demonstration of helper function in vitro. The 15 cases assigned to the B-cell lineage expressed a variety of B-cell-associated antigens, consistent with various stages of B-cell differentiation. Monoclonal antibodies OKT3, OKT4, OKT6, and OKT8 exhibited T-cell lineage restriction; and monoclonal antibodies OKB2, BL1, and B1 exhibited B-cell lineage restriction. Ia, TdT, cALLa, OKT9, and OKT10 exhibited lineage infidelity. Southern blot analysis for immunoglobulin heavy chain gene rearrangements confirmed 18 of the 19 lineage assignments made by immunophenotypic analysis and suggested that the 1 case of indeterminate phenotype was a B-cell neoplasm. One T-cell (OKT3+, T4+) neoplasm exhibited rearranged immunoglobulin heavy chain genes. Thus, neither immunophenotypic analysis nor the demonstration of rearranged immunoglobulin heavy chain genes alone permitted the satisfactory lineage assignment of every case of SIg-, E- NHL. However, combined immunophenotypic, functional, and genotypic analysis allowed us to assign every SIg-, E-NHL to the B- or T-cell lineage and to demonstrate that truly "null-cell" NHLs are probably very uncommon. PMID- 2931031 TI - Neuropeptide action in nucleus tractus solitarius: angiotensin specificity and hypertensive rats. AB - We have reported that microinjection of angiotensin II (ANG II) into the nucleus tractus solitarius of urethan-anesthetized normotensive rats produces an increase in mean arterial pressure (MAP) over the dose range 50-500 pmol. The effect in spontaneously hypertensive rats (SHR) is now reported. Over the range 100-500 pmol SHR exhibit increases in MAP and heart rate greater than Wistar-Kyoto or Sprague-Dawley rats. SHR did not exhibit exaggerated responses to intravenous phenylephrine, suggesting a central site of increased responsiveness to ANG II. We also found depressor effects in Sprague-Dawley at lower doses (0.1 and 1 pmol). The decreases in MAP were extremely variable and not dose related. A selected dose of additional neuropeptides identified in the NTS was tested. Somatostatin, bradykinin, and vasoactive intestinal peptide (0.5 nmol) were without cardiovascular effects. Oxytocin and vasopressin, however, produced significant increases in MAP. Substance P produced a very small but significant increase in heart rate and MAP. Interaction between the vasopressin and ANG II pressor effects was studied, and each proved to be independent. PMID- 2931032 TI - Atriopeptin stimulation of rectal gland function in Squalus acanthias. AB - The rectal gland of the shark plays a significant role in the homeostasis of extracellular volume. Regulation of rectal gland function is under hormonal control, but the precise identity of the humoral mediator is unknown. Atriopeptin stimulates rectal gland chloride secretion in vivo. This stimulation of epithelial transport is accompanied by systemic and local hemodynamic effects. Atriopeptin also stimulates chloride secretion by the in vitro perfused rectal gland, an effect that is not accompanied by hemodynamic changes. Extracts of shark heart, but not muscle, brain, kidney, or intestine, contain a heat-stable trypsin-sensitive substance capable of in vitro stimulation of rectal gland chloride secretion. Electron micrographic analysis reveals multiple neurosecretory-like granules in atrial cardiocytes that are only rarely seen in ventricular cardiocytes. By using the in vitro perfused gland as a biologic assay, serum obtained after extracellular volume expansion reveals the presence of a rectal gland stimulatory factor that is not present in serum before expansion. These results are consistent with the hypothesis that atriopeptin is present in shark cardiocytes and is released during volume expansion. The atriopeptin stimulates rectal gland chloride secretion, providing a negative feedback mechanism for the regulation of extracellular volume. PMID- 2931033 TI - Cellular immunity in human milk. AB - The responses of human milk lymphocytes (MIL) to a variety of immunogenic stimuli were studied and compared to those of peripheral blood lymphocytes (PBL) from the milk donors. MIL showed a decreased proliferative response to mitogens and allogeneic leukocytes in vitro but displayed the ability to stimulate alloreactivity equivalent to PBL. Neither pretreatment with cell-free autologous milk nor co-cultured MIL were capable of suppressing the proliferative responses of PBL. Moreover, macrophages isolated from milk and pulsed with soluble antigen or allogeneic cells effectively induced proliferation by peripheral blood T cells whereas the response of milk nonadherent cells to antigen presented by peripheral macrophages was very low. MIL respond better to pathogenic enteric E. coli than PBL not as well as PBL to Yersinia enterocolitica. Treatment of MIL with monoclonal antibodies cytotoxic for T cells abolished their response to bacterial antigens. Application of an anti HLA class II antigen monoclonal antibody to mixed lymphocyte or lymphocyte-bacteria cultures resulted in substantial inhibition of the MIL response similarly to that of PBL. The relevance of these data to the immunological needs of the neonate are discussed. PMID- 2931034 TI - Effects of extracorporeal circulation on plasma beta-endorphin-like immunoreactivity in children. PMID- 2931035 TI - Influence of plasma proteins on the onset of hypnotic action of intravenous midazolam. AB - The action of midazolam is influenced by serum protein binding as seen in the relationship between the time of onset of action of a fixed dose of the drug and the plasma albumin. Pretreatment with intravenous aspirin produces a decrease in the in vitro binding of midazolam. In vivo this is manifest as an increase in the rapidity of action of the benzodiazepines. Probenecid pretreatment will also cause a decrease in the onset time of midazolam. However, this is not due to altered plasma protein binding of the sedative. PMID- 2931037 TI - Regional blood flow and cerebral metabolic changes during alcohol withdrawal and following midazolam therapy. AB - Regional blood flows and cerebral oxygen consumption (CMRO2) were measured following alcohol withdrawal in alcohol-dependent rats. In addition, the authors tested the ability of midazolam (0.057, 0.575, or 5.75 mg X kg-1) to modify alcohol-induced changes. Rats received a 3-week treatment of daily ad libitum access to a liquid diet containing 6.54% ethanol or a sham treatment with the same caloric intake but with white dextrin substituted for alcohol. Regional blood flow was measured 12 h after alcohol withdrawal with radioactive microspheres. Nitrous oxide (70% in oxygen) was used as the control anesthetic. Rats withdrawn from alcohol treatment had significantly increased heart rate, cortical cerebral blood flow (CBF) (39 +/- 8%, mean +/- SE), and CMRO2 (41 +/- 9%) compared with sham-treated rats (P less than 0.05). Subcortical CBF (49 +/- 8%), myocardial (52 +/- 18%), and hepatic arterial blood flow (298 +/- 47%) also were increased in alcohol-withdrawn rats. Renal blood flow decreased 47 +/- 5%, while skeletal muscle and small intestinal blood flow were not significantly different between the two groups. Midazolam infusion decreased CBF, CMRO2, and hepatic arterial blood flow in alcohol-withdrawn rats to similar levels as sham treated rats and increased renal blood flow in both groups. Skeletal muscle and intestinal tissues showed no change in blood flow in response to midazolam. The authors conclude that midazolam may be effective in lowering blood pressure and brain metabolism and reversing regional blood flow changes produced by alcohol withdrawal in the rat. PMID- 2931036 TI - Haemodynamic changes during induction of anaesthesia with midazolam and diazepam (Valium) in patients undergoing coronary artery bypass surgery. AB - Midazolam 0.3 mg/kg and diazepam 0.5 mg/kg were used for induction of anaesthesia in two groups of 10 patients each undergoing coronary artery bypass surgery. Haemodynamic variables were measured during induction of anaesthesia, after pancuronium and following tracheal intubation. Haemodynamic indices were derived from these measurements using standard formulae. The induction of anaesthesia with midazolam produced a slight but significant increase in heart rate. There was a significant fall in systemic arterial pressure and pulmonary artery pressure following both drugs. Despite the fall in systemic arterial pressure, the cardiac index was maintained in patients who received midazolam. The cardio stimulatory effect of laryngoscopy and tracheal intubation was not prevented by either of the benzodiazepines and morphine in the dosage used. Midazolam is a suitable alternative to diazepam as part of an intravenous induction regimen in patients with ischaemic heart disease. PMID- 2931038 TI - Complex coronary angioplasty: a technique for dilatation of bifurcation stenoses. AB - Bifurcation stenoses have been recognized to be at "high risk" for acute closure during percutaneous transluminal coronary angioplasty. Use of the traditional single balloon technique in such situations often results in acute closure or worsening of the stenosis in the other branch. A technique utilizing simultaneous inflation of two balloons, ("kissing balloon" technique) has been utilized to avoid this complication. A double balloon technique has been developed using sequential inflations rather than simultaneous inflations to preserve the integrity of both branches while avoiding the arterial trauma produced by inflating two balloons in a small artery simultaneously. Twelve of 13 bifurcation stenoses were successfully treated with this sequential inflation double balloon technique. (Primary success rate = 92%). PMID- 2931039 TI - Causes of death from asthma in children. AB - There were seven deaths from asthma at Children's Hospital National Medical Center from 1944 to 1984. There have been none since 1971 despite an increased frequency of admissions for the treatment of asthma. Review of records implicated undertreatment, infection, and sedation as factors that may have contributed to deaths. PMID- 2931040 TI - Procaterol metered-dose inhaler in adults with asthma. AB - Procaterol hydrochloride is a new sympathomimetic amine which is highly selective for beta-2 receptors. The drug has been previously studied in the oral dosage form and has been found to be an effective bronchodilator with a prolonged duration of action. The present study evaluated the procaterol metered-dose inhaler (in comparison to placebo) in 30 adult patients with asthma during a 2 week treatment period. The drug was shown to be an effective bronchodilator with a prolonged duration of action. PMID- 2931041 TI - Carbon dioxide embolism during laparoscopy and hysteroscopy. AB - Venous carbon dioxide embolism is a rare but potentially lethal complication of laparoscopy. The risk is increased when it is associated with hysteroscopy. A case is presented of a young women undergoing laparoscopy and hysteroscopy for infertility. Cardiovascular collapse and cardiac arrest, associated with a mill wheel murmur, occurred during hysteroscopy at the time of a change of position. The patient had irreversible brain damage and died a week later. Early diagnosis and prevention of this serious complication are discussed. PMID- 2931042 TI - Urinary incontinence in the elderly. Bladder-sphincter biofeedback and toileting skills training. AB - Behavioral treatment of urinary incontinence was given to 39 elderly outpatients; 19 had stress incontinence, 12 detrusor motor instability, and 8 urge incontinence without instability. Biofeedback involving the bladder and sphincter was used to teach selective control of sphincter muscles or voluntary inhibition of detrusor contractions. Traditional behavioral methods used included habit training to gradually increase the voiding interval and relaxation training to cope with the urge to void. After an average 3.5 training sessions, patients with stress incontinence reduced the frequency of incontinent episodes an average of 82% (range, 55% to 100%). Patients with detrusor motor instability showed an average 85% improvement (range, 39% to 100%), and patients with urge incontinence reduced incontinence an average of 94% (range, 83% to 100%). Furthermore, 13 of the patients achieved total continence, and 19 had fewer than one accident per week after treatment. PMID- 2931043 TI - Ulcerative colitis and abnormal helper:suppressor cell ratios in a husband and wife. PMID- 2931044 TI - Oedipism and Down's syndrome: case report and review of the literature. AB - Patients with Down's syndrome usually have mild and pleasant temperaments, rarely exhibiting temper tantrums or behavioral problems. Blindness occurs in 5% of these patients. When present, it is usually due to keratoconus and cataracts and their associated complications. In this paper the authors report a case of self induced ocular blindness that apparently resulted from the patient's severe mental retardation. To their knowledge, this has not been described in Down's syndrome. PMID- 2931045 TI - [Mechanisms of aspirin intolerance]. AB - Aspirin intolerance brings on cutaneous and/or respiratory reactions. The mechanisms are to be elucidated precisely, but are not IgE-mediated. 193 patients with nasal polyps are studied. With systematic aspirin oral challenge, 27% belong to the classical triad: asthma, polyps and aspirin sensitivity. Other drugs or chemicals intolerance are associated in 42%: alcohol, metabisulfites, benzoates, tartrazine, codeine... A link with the non-allergic eosinophilic rhinitis is suggested. A short review of several pathogenic hypothesis is discussed. Among a comparative study, the authors showed that the aspirin-intolerant patients' platelets have a quite normal arachidonic acid metabolism. The clue is probably towards an abnormal instability of cells membranes and excessive receptors sensitivity to leukotrienes. PMID- 2931046 TI - Open, prospective study of the clinical efficacy of ciprofloxacin. AB - One hundred patients with infections mostly outside of the urinary tract were studied in a prospective, open manner to ascertain the effectiveness and safety of ciprofloxacin in a variety of clinical situations. There were 41 instances of bacteremia, including 38 with Salmonella typhi, and 21 respiratory, 17 skin and skin structure, 11 bone or joint, 6 gastrointestinal, and 4 urinary tract infections. The patients were given 500 mg of ciprofloxacin orally every 12 h for 2 to 107 days (mean, 15.1 days). Microorganisms isolated disclosed susceptibilities comparable to those reported previously, with a MIC for 90% of the strains of 0.25 microgram/ml. For Streptococcus pneumoniae the MIC for 90% of the strains was 0.03 microgram/ml, and it was higher for Pseudomonas aeruginosa (0.5 microgram/ml), although still in the therapeutic range. Levels in blood were lower than those reported in other series, and no accumulation of the drug during treatment was detected. In 88 instances there was resolution of the infectious process, in 7 there was improvement, in 3 there was a failure to respond, and in 2 the clinical response was indeterminate. Bacteriological eradication was documented in 87 infections. Despite extensive clinical and laboratory examinations before, during, and after therapy, no major abnormalities related to therapy were seen; only one patient required discontinuation of ciprofloxacin due to gastrointestinal intolerance. Ciprofloxacin is an effective and safe therapeutic alternative in many tissue infections caused by susceptible microorganisms. PMID- 2931048 TI - Mechanistic investigation on the temperature dependence and inhibition of corn root plasma membrane ATPase. AB - The kinetics of corn root plasma membrane-catalyzed Mg-ATP hydrolysis may be satisfactorily described by a simple Michaelis-Menten scheme. It was found that the Km of the process was relatively insensitive to changes in temperature. This property allowed us to conveniently estimate the activation energy of the enzyme turnover process as approximately 14 kcal mol-1 in the temperature range of 10 to 45 degrees C. The enzyme activity was inhibited by the presence of diethystilbestrol (DES), miconazole, vanadate, and dicyclohexylcarbodiimide (DCCD). The inhibition caused by DES and miconazole was strictly uncompetitive and inhibition by vanadate was noncompetitive. The inhibition by DCCD showed a substrate concentration dependence, i.e., competitive at high and uncompetitive at low concentrations of Mg-ATP. The 1/V vs [I] plots suggested that there were different but unique binding sites for DES, vanadate, and miconazole. However, the modification of the plasma membrane by DCCD exhibited interaction with multiple sites. Unlike yeast plasma membrane ATPase, the enzyme of corn root cells was not affected by the treatment with N-ethylmaleimide. Although the enzyme activity was regulated by ADP, a product of the reaction, the presence of inorganic phosphate showed no inhibition to the hydrolysis of Mg-ATP. PMID- 2931047 TI - Pharmacokinetics of three oral formulations of ciprofloxacin. AB - We compared the absorption of three formulations of ciprofloxacin after oral administration in 18 normal adult male volunteers. Each subject received 500 mg of ciprofloxacin as two 250-mg tablets, one 500-mg tablet, or a solution in a randomized crossover sequence. Pharmacokinetic parameters were determined by model independent methods. Because a solution is considered to be the ideal oral dosage form, the results determined for the tablets were compared to those for the solution. Mean values for the maximum concentration of drug in serum, the time to maximum concentration of drug in serum, and the elimination half-life were 3.23 micrograms/ml, 1.00 h, and 5.04 h, respectively, for the solution. The mean renal clearance of ciprofloxacin was 372 ml/min and accounted for at least 50% of the total clearance. We recovered 44.4, 48.6, and 55.8% of the administered ciprofloxacin from the urine as unchanged drug within 24 h after dosing with the 250-mg tablets, 500-mg tablets, or solution, respectively. The 500-mg tablets were found to be bioequivalent to the solution with regard to all pharmacokinetic parameters. The 250-mg tablet was not bioequivalent to either of the other formulations; the relative bioavailability values were 78.7 and 74.1%, respectively, for the 500-mg tablet and the solution. The clinical significance of this difference in bioavailability is yet to be determined. PMID- 2931049 TI - Dicyclohexylcarbodiimide-sensitive ATPase in Halobacterium saccharovorum. AB - Membranes from Halobacterium saccharovorum contained a cryptic ATPase which required Mg2+ or Mn2+ and was activated by Triton X-100. The optimal pH for ATP hydrolysis was 9-10. ATP or GTP were hydrolyzed at the same rate while ITP, CTP, and UTP were hydrolyzed at about half that rate. The products of ATP hydrolysis were ADP and phosphate. The ATPase required high concentrations (3.5 M) of NaCl for maximum activity. ADP was a competitive inhibitor of the activity, with an apparent Ki of 50 microM. Dicyclohexylcarbodiimide (DCCD) inhibited ATP hydrolysis. The inhibition was marginal at the optimum pH of the enzyme. When the ATPase was preincubated with DCCD at varying pH values, but assayed at the optimal pH for activity, DCCD inhibition was observed to increase with increasing acidity of the preincubation medium. DCCD inhibition was also dependent on time of preincubation, and protein and DCCD concentrations. When preincubated at pH 6.0 for 4 h at a protein:DCCD ratio of 40 (w/w), ATPase activity was inhibited 90%. PMID- 2931050 TI - Vanadyl and vanadate inhibit Ca2+ transport systems of the adipocyte plasma membrane and endoplasmic reticulum. AB - Vanadate and vanadyl have many insulin-mimetic effects on cellular metabolism and also have been shown to alter cellular Ca2+ fluxes. In this report, vanadate and vanadyl, like insulin, are shown to inhibit the plasma membrane (Ca2+ + Mg2+) ATPase/Ca2+ transport system as well as Ca2+ transport by endoplasmic reticulum from rat adipocytes. Ca2+ transport by the endoplasmic reticulum was inhibited half-maximally (I50) by vanadate and vanadyl at concentrations of 30 and 33 microM, respectively. Inhibition of the plasma membrane Ca2+ transport by vanadate and vanadyl was less sensitive, with I50 values of 144 and 92 microM, respectively. These I50 values for plasma membrane Ca2+ transport were similar when measured under conditions of calmodulin-stimulated and non-calmodulin stimulated Ca2+ transport. The predominant effect of both ions on the kinetic parameters of Ca2+ transport was a substantial decrease in the Vmax by 43-46% for both transport systems. An increase in intracellular Ca2+ following the inhibition of the (Ca2+ + Mg2+)-ATPase/Ca2+ pump in the plasma membrane and endoplasmic reticulum by these vanadium ions may result, at least in part, in the observed insulin-mimetic alterations in cellular metabolism. PMID- 2931051 TI - [Treatment of meningeal carcinomatosis--neocarzinostatin perfusion therapy in the CSF pathway]. AB - The authors presented the results of perfusion chemotherapy in the CSF pathway with neocarzinostatin (NCS) for the treatment of meningeal carcinomatosis. In three cases of stomach cancer and one case of malignant lymphoma, cranial polyneuropathy, progressive hydrocephalus and positive cytology of the CSF were found during treatment of malignant tumors. NCS therapy was performed by means of perfusion from the spinal subarachnoid space to the ventricle utilizing Ommaya's reservoir, or simply by repeated lumbar punctures. In all of four cases the number of malignant cells in the CSF was significantly diminished, and temporary neurological improvement was observed until the patient's death due to advanced primary lesions. These results indicated that in cases of meningeal carcinomatosis, NCS perfusion therapy using the CSF pathway was a much more favorable method than treatment with other chemotherapeutic agents with less noticeable side effects. PMID- 2931052 TI - Acne secondary to white petrolatum use. PMID- 2931053 TI - Dermatitis produced by applications of monobenzone in patients with active vitiligo. AB - Six patients with spreading vitiligo treated with applications of monobenzone developed a vesicular dermatitis. The eruption was restricted exclusively to the pigmented areas of the skin. Patch tests applied to pigmented and depigmented skin produced an inflammatory response only within the pigmented areas. The explanation for this puzzling phenomenon is not known. PMID- 2931054 TI - Total thyroidectomy in irradiated patients. A twenty-year experience in 206 patients. AB - During a period of 20 years (1965-1985), 206 consecutive patients were operated on for radiation-associated nodular thyroids. The ages ranged between 8 and 76 years (mean 38.7). there were 136 women and 70 men. The average duration between radiation exposure and operation was 27 years. The operations performed were total thyroidectomy (192) or, in patients who had undergone a previous lobectomy in another institution, another lobectomy (14). In addition, 25 patients required a neck dissection for nodal metastases and 27 underwent simultaneous subtotal parathyroidectomy for coexistent hyperparathyroidism. The pathologic findings were: 87 (42.2%) carcinoma (73 papillary, 13 follicular, 1 undifferentiated); 92 (44.7%) follicular adenomas; and 27 (13.1%) thyroiditis. To date, with an average follow-up of 6 years (0.5-31 years), only two patients have expired from recurrent disease. A third died of unrelated cause. A comparison of the first 100 patients (12 years) with the last 106 patients (8 years) demonstrated that the incidence of carcinoma has dropped from 48 to 37%, the incidence of lymph node metastases has decreased from 35 to 26%, and the incidence of bilaterality has fallen from 75 to 54%. On the basis of this series, it was concluded that total thyroidectomy is still indicated for radiation-associated nodular thyroids. However, if the trend of decreasing incidence, bilaterality, and metastatic disease persists, this approach may have to be reevaluated in the near future. PMID- 2931055 TI - Predicting tumor response in patients with colorectal hepatic metastases. AB - Until now, there has been no reliable means of predicting tumor response to chemotherapy in patients with metastatic colorectal cancer. Using arterial nuclide flow scans as a determinant of tumor response, the degree of tumor perfusion was evaluated in a blinded prospective study. Seventy-three patients with colorectal hepatic metastases received continuous hepatic arterial (N = 52) or systemic intravenous (N = 21) chemotherapy using an implantable pump. All patients had pretreatment hepatic arteriography and arterial flow scans using 99mTc macroaggregated albumin (99mTc-MAA). An arteriogram was characterized as positive if it showed tumor hypervascularity; the 99mTc-MAA flow scan was considered positive if it showed increased tumor uptake relative to the liver. Of 47 patients with an evaluable 99mTc-MAA flow scan who were treated with arterial infusion, 31 had a positive scan; in this group 16 responded to chemotherapy. The 99mTc-MAA scan was negative in 16 patients, of whom one responded to chemotherapy (p less than 0.006). The 99mTc-MAA scan had the greatest predictive value in previously untreated patients (sensitivity = 91%; specificity = 77%). The arteriogram was positive in 25 of 46 evaluable patients, but this finding had little predictive value for tumor response (sensitivity = 56%; specificity = 46%). Of 21 patients receiving systemic intravenous infusion, the scan was positive in nine patients, of whom seven responded to chemotherapy. The 99mTc-MAA scan was negative in 12 patients, of whom one responded to chemotherapy (sensitivity = 88%; specificity = 85%). When 99mTc-MAA-positive and -negative groups were compared, there were no differences in mean patient age, per cent liver involvement, tumor size, or plasma liver function tests. Hepatic tumor perfusion as determined by MAA arterial flow scan is a reliable predictor of tumor response in patients with metastases from large bowel cancer. The test provides a valuable criterion for selecting individuals for treatment of metastases from large bowel cancer by infusion chemotherapy. PMID- 2931056 TI - Delineation of peripheral and coronary detail by intraoperative angioscopy. AB - In this study, the development of intraoperative angioscopy, the value of the information obtained, and the problems encountered with the procedure are reported. Eight angioscopes, 1.5 to 2.8 mm in diameter, with a line resolution of greater than 0.4 mm at 5 mm, were used. One-hundred ten angioscopic investigations were performed in 46 patients; 24 at peripheral bypass surgery and 22 at coronary artery bypass surgery. These included 68 arteries, 28 new anastomoses, six old grafts, five laser angioplasties, and three in situ vein grafts. The most important finding was that angioscopic data provide information not available from probes or angiography. Angioscopic findings were responsible for a change in surgical procedures in 12 patients (26%) including three anastomotic revisions, three alterations in graft site placement, and two repeat thrombectomies. The most significant technical problems were lack of steerability and insufficient irrigation, which resulted in poor angiographic images. Further technical development is necessary before routine intraoperative angioscopy is practical. Nevertheless, if these problems are resolved, angioscopy will provide unique, high-resolution information which can directly alter surgical therapy. PMID- 2931057 TI - [Immediate coronary angioplasty in the acute phase of myocardial infarction. French multicenter study: December 1983]. AB - Following the introduction of intracoronary thrombolysis in the acute phase of myocardial infarction (AMI), transcutaneous coronary angioplasty (TCA) was originally conceived as a logical complementary procedure to treat residual stenosis and so prevent the frequent post-thrombolysis reocclusion (20-30 p. 100 of cases). With increasing experience TCA of first intent appeared rational, more rapid and effective, ensuring coronary recanalisation (CR), suppression of residual stenosis and the prevention of reocclusion in the same procedure with with the objective of reducing the number of coronary bypass grafts (CBG) in patients with single vessel disease. A French multicentre study of 22 cases was organised by 9 centres. The average period between onset of symptoms and intervention was 2 hours 10 mins (range 30 mins-5 hours 30 mins). The average duration of the procedure was only 30 mins. 16 patients had anterior and 6 patients inferior AMI. Coronary angiography showed 12 occlusions (54.5 p. 100) and 10 sub-occlusions with 6 cases of delayed opacification. All patients had successful initial TCA with no major complications. The arterial occlusions decreased from 100 p. 100 to 31 p. 100 and the subocclusions from 94 to 12 p. 100. 2 patients died in the hospital period, one at the 48th hour of controlateral AMI and the other one at the 5th day of reocclusion. Three patients developed reocclusion at the site of the original TCA. Complete regression of ECG changes was observed in 31.8 p. 100 of cases. Complete recovery of normal left ventricular function was observed in 8 of the 17 patients who underwent follow-up investigations (47 p. 100 of cases).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2931059 TI - [Tricuspid insufficiency in posterior infarction caused by occlusion of the right coronary artery. Anatomical study]. AB - Thirty-one autopsy cases of patients (20 men, 11 women) who died within 5 days of the onset of primary posterior wall myocardial infarction due to occlusion of the right coronary artery (RCA) were divided into two groups: Group A (19 cases) with associated right ventricular infarction and Group B 812 cases) without right ventricular extension of the infarct. The causes of death were practically identical in the two groups except for cardiac rupture which was always septal and more common in Group A. In Group A, the complete occlusion of the RCA was always proximal to (18 cases) or at the site of origin (1 case) of the right marginal artery. Twelve cases (63 p. 100) of tricuspid regurgitation were detected in Group A but there were no such cases in Group B. Tricuspid regurgitation was associated with a significantly poorer short term prognosis. It was not related to a greater degree of dilatation of the tricuspid ring but to more severe septal and right ventricular infarction causing prolapse of the septal and posterior septal leaflets into the right atrium. A second group of autopsy cases comprised 40 patients dying in the long term (1 to 14 years later) after primary posterior wall infarction. In 15 cases (Group A) the post-mortem study showed chronic right ventricular infarction, an extension of a chronic left ventricular infarct. These findings were absent in the other 25 cases (Group B). The mean survival times (Group A : 6.1 years, Group B : 5.9 years) were comparable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2931058 TI - [Evaluation of left ventricular mass by M-mode and bidimensional echocardiography]. AB - The aim of this study was to validate an echocardiographic method of evaluating LV mass by assessing the reproducibility and comparing the results with those of angiography. 20 patients without abnormal regional wall motions or asymmetric septal hypertrophy underwent left ventriculography in the RAO plane and three successive M mode and 2D echocardiograms. Three 2D echo methods of measuring volumes and mass were used: the monoplane ellipsoid model obtained from apical views, the biplane ellipsoid model from an apical and a short axis parasternal view and the hemi-ellipsoid-cylinder model (HEC). The M mode evaluations showed good reproducibility with respect to volume (variation coefficient (VC): inter observer 9.8 p. 100 and intra patient 15.6 p. 100). The reproducibility of 2D echo measurements was much poorer (intra patient volume: VC = 34 to 45 p. 100; mass 29 to 46 p. 100). A close correlation was observed between the results of M mode echo and angiography; volume r = 0.85, SD = 60 g. With respect to the 2D method, the best results were obtained with the HEC model; volume r = 0.90, SD = 31 ml; mass r = 0.82, SD = 41 g. We suggest a method combining the M mode and 2D techniques, using a HEC model in which the long axis is obtained by 2D echocardiography and the short axis and wall thickness by M mode recordings. The following correlations with the angiographic method were obtained: volume r = 0.91, SD = 36 ml; mass r = 0.89, SD = 27 g.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2931060 TI - [Adult pulmonary valvular stenosis, major stenosing right ventricular hypertrophy and tricuspid insufficiency. Apropos of 2 cases]. AB - 2 cases of severe pulmonary valvular stenosis in two young adults aged 21 and 29 years respectively are presented. Despite the degree of stenosis (4 mm jet), the right ventricular pressures did not exceed systemic pressures because of severe tricuspid regurgitation. This dominated the clinical and anatomical findings, causing aneurysmal dilatation of the right atrium and displacement of the tricuspid valve to the left. The diagnosis of Ebstein's anomaly was raised in one case but excluded by echocardiography and angiocardiography. In spite of the severity of the symptoms and peripheral clinical signs, surgery of the right ventricular outflow tract, tricuspid valvuloplasty and resection of part of the right atrium led to a complete and rapid cure, confirmed by catheterisation one month after operation. PMID- 2931061 TI - Thermography in low back pain and sciatica. AB - This investigation proved that thermography is a reliable method of examination. When the difference of temperature in the legs reached 1 degree C or more, there was a correlation between clinical sciatica and the thermographic registration in 51 of 52 patients. As regards diagnosing the level, thermography is unreliable for distinguishing an L4/L5 syndrome from an S1 syndrome. In this investigation it was possible to correlate colder zones and the clinical syndrome in most patients. However, there is a large overlap between the dermatomes. When following up the results of autotraction no certain conclusions can be drawn, but among the patients with sciatica the decrease in temperature was greater in the group who clinically recovered. PMID- 2931062 TI - Cognitive evoked potentials (P300) in early Huntington's disease. AB - The P3 component of both auditory-event- and visual-event-related potentials of 13 patients with Huntington's disease was studied and compared with the P3 component of normal patients. The latencies of the patients' P3 components were compared with the latency-age regression lines generated by the normal population in both modalities. A P3 latency was considered abnormal if it fell above the 2 SE limit for the latency-age regression line. The incidence of normal or abnormal P3 latencies in the two modalities was compared with the results of computed tomography, electroencephalography, and neuropsychological testing. Nine patients had abnormal P3 latencies and ten patients had abnormal visual P3 latencies, with seven having abnormal latencies on both tests and 12 having abnormal latencies on one of the two tests. An abnormal P3 latency in one modality did not imply an abnormal P3 latency in the other. An abnormality of the P3 latency did not correlate with an abnormality in results from computed tomography, electroencephalography, or neuropsychological testing. PMID- 2931063 TI - Effect of sulindac on the permeability of the blood-retinal barrier in early diabetic retinopathy. AB - To study the effect of sulindac on the alteration of the blood-retinal barrier, 24 insulin-dependent diabetic patients with minimal or no retinopathy were randomly assigned to receive either oral sulindac (200 mg twice daily) or a placebo for a period of six months. All patients underwent fundus photography, fluorescein angiography, and vitreous fluorophotometry before treatment and after 1, 3, and 6 months of treatment. Vitreous fluorophotometry data showed that there were fewer alterations of the blood-retinal barrier in the sulindac group compared with the placebo group during the six-month study period. PMID- 2931064 TI - A comparative study on the NAD glycohydrolase of the maternal and neonatal erythrocytes. PMID- 2931065 TI - Dental treatment for the elderly. PMID- 2931066 TI - Low back pain. PMID- 2931067 TI - Mixed lymphocyte reaction suppression by tumour cell lines from naturally occurring squamous cell carcinomata. AB - Seven epithelial tumour cell lines derived from naturally occurring ovine squamous cell carcinomata (OSCC) were examined for their ability to stimulate allogeneic lymphocytes in vitro. All cell lines failed to stimulate any proliferative response; a failure which was not due to the absence of alloantigens on the tumour cells. It was found, however, that the cell lines tested caused a marked suppression of a third party mixed lymphocyte reaction. This suppression was mediated only by live tumour cells since the addition of heat-killed tumour cells had no effect on the response. PMID- 2931068 TI - My initiation to the malocclusion, dental distress and TMJ problem. PMID- 2931069 TI - Dental kinesiology. PMID- 2931070 TI - Uses of applied kinesiology for dentists. PMID- 2931071 TI - Coping with stress through progressive relaxation, with comments on behavior modification and biofeedback. PMID- 2931072 TI - TMJ from an orthodontic perspective using cephalometric laminagraphy. PMID- 2931073 TI - Dural fibrillation. PMID- 2931074 TI - Good health--your responsibility! PMID- 2931075 TI - Peer interventions. Increasing social behaviors in multihandicapped children. PMID- 2931077 TI - Mathematical modeling of mitochondrial energy transduction. AB - A mathematical model of mitochondrial energy transduction is presented. The model contains rate equations for the main steps of oxidative phosphorylation. It was used to simulate the relations of respiration and ATP formation to extra- and intramitochondrial ATP/ADP ratios under various steady-state conditions. Furthermore, the model equations allowed to compute control coefficients, which quantify the control exerted by different steps on respiration. The distribution of control within mitochondria is demonstrated to depend on the metabolic state of mitochondria and also on the properties of extramitochondrial enzymes involved in ATP turnover. The simulated steady-state data as well as computed control coefficients were found in close agreement with experimental data. PMID- 2931076 TI - Isoenzymes of phosphofructokinase in the rat. Demonstration of the three non identical subunits by biochemical, immunochemical and kinetic studies. AB - In man and the rabbit, 6-phosphofructokinase (PFK, EC 2.7.1.11) exists in tetrameric isoenzymic forms composed of muscle (M or A), liver (L or B) and platelet or brain (P or C) subunits, which are under separate genetic control. In contrast, the genetic control of the rat PFK has not yet been conclusively established; it is unclear whether the P-type or C-type subunit exists in this species. To resolve this question, we investigated the enzyme from the skeletal muscle, liver and brain of rats of Wag/Rij strain. Our studies demonstrate that the rat PFK is also under the control of three structural loci and that the homotetramers M4, P4 and L4 exhibit unique chromatographic, immunological and kinetic-regulatory properties. Skeletal-muscle and brain PFKs consist of isolated M4 and P4 homotetramers respectively. Although liver PFK consists predominantly of L4 homotetramer, it also contains small amounts of PL3 and P2L2 species. All three PFKs exhibit allosteric properties: co-operativity with fructose 6 phosphate and inhibition by ATP decrease in the order P4 greater than L4 greater than M4. P4 and M4 tetramers are the most sensitive to citrate inhibition, whereas L4 tetramer is the least sensitive. More importantly, P4 and L4 isoenzymes are the most sensitive to activation by fructose 2,6-bisphosphate, whereas M4 isoenzyme is the least sensitive. These results indicate that the brain PFK in this strain of rat is a unique tetramer, P4, which also exhibits allosteric kinetics, as do the well-studied M4 and L4 isoenzymes. The reported differences in the number and nature of isoenzymes present in the rat brain and liver most probably reflect the differences in the strains studied by previous investigators. Since the nature of the rat PFK isoenzymes and nomenclatures reported by previous investigators have been now reconciled, it is proposed that, for the sake of uniformity, only well-established nomenclatures used for the rabbit or human PFK isoenzymes be used for the rat isoenzymes. PMID- 2931078 TI - Mathematical models of metabolic systems: general principles and control of glycolysis and membrane transport in erythrocytes. AB - General methods for the mathematical modeling of metabolic systems are discussed. Attention is paid to the simulation of steady states as well as time dependent behaviour of biochemical reaction networks. Control coefficients are used for the quantitative evaluation of the parameter dependence of model variables. The methods are applied to the mathematical analysis of the energy metabolism of erythrocytes. New results are presented concerning the interaction of glycolysis and osmotic behaviour of the red cell (metabolic-osmotic model). A general method for the calculation of control coefficients is developed which gives the basis also for the interpretation of control coefficients using chains of causal actions. PMID- 2931079 TI - Protease-activated protein kinase in rat liver plasma membrane. AB - Upon limited proteolysis with trypsin, a cAMP and Ca2+-independent protein kinase was produced from rat liver plasma membrane. This enzyme showed a multifunctional capacity and phosphorylated calf thymus histone and rat liver ribosomal proteins. The molecular weight was estimated to be 5.0 X 10(4). When plasma membrane was treated with a buffer containing Triton X-100, a proenzyme with a molecular weight of 8.4 X 10(4) was extracted. By tryptic digestion, the proenzyme was converted to an active protein kinase which was similar to the enzyme obtained by the direct digestion of membrane. However, this proenzyme phosphorylated H1 histone in the presence of Ca2+ and phospholipid without proteolytic digestion. These results indicate the existence of a protease-activated protein kinase in rat liver plasma membrane and the proenzyme seems to be same as protein kinase C. PMID- 2931080 TI - Narcan inhibition of human liver alcohol dehydrogenase. AB - Narcan, the pharmaceutical agent for the administration of naloxone, has been reported to antagonize ethanol intoxication. In addition to naloxone, Narcan contains the antioxidant esters methyl- and propylparaben. Pure naloxone and these two esters were examined for their capacity to inhibit ethanol oxidation by purified isozymes of human liver alcohol dehydrogenase (ADH). Naloxone (400 micromolar) fails completely to inactivate any of the three ADH isozyme classes. In contrast, methyl- and propylparaben, and some related esters, competitively inhibit the oxidation of ethanol and reduction of acetaldehyde by all isozymes examined. The reported effects of Narcan on ethanol-intoxicated animals or cells cannot be attributed to the action of naloxone. PMID- 2931081 TI - Superhelical DNA-dependent ATPase from calf thymus. AB - Two physically and catalytically distinct DNA-dependent ATPases were isolated from a purified preparation of calf thymus poly(ADP-ribose) polymerase. A unique feature of these two ATPases was the high stimulation by supercoiled DNA. Other nucleic acids (including denatured DNA and ribosomal RNA) and certain polynucleotides differentially stimulated the two enzymes. We have not detected any other DNA-related activity associated with these ATPases. PMID- 2931082 TI - Chemical synthesis of a mitochondrial gene designed for expression in the yeast nucleus. AB - A novel DNA sequence coding for subunit 8 of the mitochondrial ATPase of Saccharomyces cerevisiae has been constructed by chemical synthesis. The synthetic gene, termed NAP1, is designed for expression in the yeast nucleus and codes for a 48 amino acid polypeptide identical to that encoded by the mitochondrial aap1 gene of S. cerevisiae. The codons chosen for the NAP1 sequence correspond almost exclusively to those most frequently occurring in highly expressed yeast genes. The NAP1 coding region differs in 31 codons from that of aap1, and is flanked by sequences carrying restriction enzyme sites useful for cloning and for gene expression. A 170 bp double stranded DNA molecule was constructed by assembling 12 oligonucleotides (12 to 45 bases in length) in a single annealing/ligation mixture. This synthetic gene will provide a route for the systematic manipulation, through in vitro mutagenesis, of the structure of a protein normally encoded by mitochondrial DNA. PMID- 2931083 TI - Ascorbic acid-Fe2+ treatment mimics effect of vitamin E deficiency on sarcoplasmic Ca-ATPase of rabbit muscle. AB - After 90 min treatment with ascorbic acid and FeSO4 at 4 degrees C, the activity of rabbit sarcoplasmic reticulum Ca-ATPase was reduced to 22% and the Arrhenius plot of enzyme activity showed an absence of a discontinuity. The presence of vitamin E restored enzyme activity (60%) and the discontinuity in the Arrhenius plot. Ca-ATPase reconstituted with delipidated protein from ascorbic acid-Fe treated preparation and normal lipid exhibited properties similar to the intact treated enzyme, whereas that reconstituted with delipidated normal protein and lipid from treated preparation exhibited reduced activity but retained the Arrhenius discontinuity. These properties are similar to those observed for sarcoplasmic reticulum Ca-ATPase from the vitamin E-deficient muscular dystrophic rabbit. PMID- 2931084 TI - Delipidization of membrane glycoproteins solubilized in acidified chloroform/methanol. Preparation of N-retinylidene opsin in a water soluble form without-detergent. AB - Bovine retina membrane proteins and glycoproteins were insoluble in chloroform/methanol (2:1, v/v) unless the membrane suspension was precipitated with trichloroacetic acid and the organic solvent mixture added to the precipitated membranes. The presence of millimolar amount of trichloroacetic acid in the organic solvent led to the total solubilization of membranes. The glycoproteins precipitated at the interphase after partition of the acidified chloroform/methanol solution with water and were resolubilized from the interphase with chloroform/methanol/water (1:1:0.3, by vol). The solubility properties of the membrane glycoproteins in the acidified organic solvent mixtures allow to remove the bulk of membrane lipids and to recover from the chloroform/methanol/water solution the glycoprotein of rod outer segment membranes, rhodopsin, as protonated N-retinylidene opsin in a water soluble form. PMID- 2931085 TI - Effects of neonatal treatment with 6-aminonicotinamide on basal and isoproterenol stimulated ornithine decarboxylase activity in cerebellum of the development rat. AB - 6-Aminonicotinamide (6-AN) is a nicotinic acid (vitamin B3) antagonist which, when administered to immature animals, has a profound influence on brain development. To explore the biochemical mechanisms which underlie these actions, we evaluated effects of 6-aminonicotinamide on ornithine decarboxylase, an enzyme involved in cellular replication and differentiation. The cerebellum of the neonatal rat was chosen for study because it represents a brain region which undergoes major maturational events postnatally. When given to neonatal rats, 6 aminonicotinamide (10 mg/kg, i.p., on days 1, 3, 5 and 7) caused a prompt and persistent inhibition of the enzyme well in advance of adverse effects on tissue weight or on general growth. In addition, the ability of the cerebellum to respond to trophic stimulation by a beta-adrenergic agonist, isoproterenol, was attenuated markedly. Assessment of cerebellar morphology indicated an early adverse effect of 6-AN on granule' cell division, resulting in eventual disruption of the characteristic laminar structure of this brain region. These data support the view that reduced ornithine decarboxylase activity and impairment of its reactivity to growth stimuli participate in the toxic effects of 6-aminonicotinamide on brain development. PMID- 2931086 TI - Observer variability in the interpretation of lumbar spine radiographs. PMID- 2931087 TI - Intraarticular variation in synovitis. Local macroscopic and microscopic signs of inflammatory activity are significantly correlated. AB - Multiple biopsy specimens from various parts of the synovial membrane were sampled under direct vision during arthroscopic surveying of the inflamed knee joints of 12 patients with various arthritides. Considerable variation in the macroscopic signs of inflammatory activity was found within the single joint. However, there was a highly significant correlation (P less than 0.001) between local macroscopic signs of inflammatory activity and microscopic signs (by immunohistochemical analysis of the corresponding tissue sample). The profound intraarticular variation in inflammatory activity was seen irrespective of clinical diagnosis. An immunohistologic pattern comprising foci of T helper cells, associated immunoglobulin-bearing cells, and HLA-DR-expressing dendritic cells was not specific for rheumatoid arthritis or any other diagnosis, but was found in the biopsy samples from sites that macroscopically demonstrated maximal inflammatory activity. PMID- 2931088 TI - [Viral type particles in the germinal centers during a lymphadenopathic syndrome related to AIDS]. AB - The identification of virus-like particles in the germinal centers of an AIDS related lymph node with histological findings of group IA is reported. A 23 year old man, intravenous drug user, presents an inversion of T helper/T suppressor cell ratio and a peripheral generalized lymphadenopathy, suggesting a diagnosis of ARC. Lymph node biopsy shows follicular hyperplasia and features consistent with group IA of AIDS-related lymphadenopathy. Immunohistochemical study reveals an increase of intrafollicular T8+ lymphocytes. Electronmicroscopic examination of follicles demonstrates the presence of particles showing features of viral nucleocapsids; these particles are seen between the cytoplasmic processes of follicular dendritic cells. Pathologic findings associated with lymphoid follicular hyperplasia in AIDS prodromal period are examined. The importance of lymph node biopsy with histological, immunohistochemical and ultrastructural studies, in patients at high risk for AIDS, is demonstrated. The detection of type D viral particles suggestive of retrovirus is in accordance with results of virologic studies which indicate the involvement of a retrovirus (called LAV or HTLV III) in the etiology of the disease. PMID- 2931089 TI - Antagonism of the LSD cue by putative serotonin antagonists: relationship to inhibition of in vivo [3H]spiroperidol binding. AB - In two groups of rats trained to discriminate 0.08 or 0.16 mg/kg of lysergic acid diethylamide (LSD) from saline, pirenperone and ketanserin completely blocked the stimulus effect of LSD. Pizotifen (BC-105) blocked the LSD cue when the training dose was 0.08 mg/kg, but had variable effects in the 0.16 mg/kg of LSD-trained group. The antagonism of the 0.08 mg/kg cue occurred at doses of the antagonists which blocked [3H]spiroperidol labeled 5-HT2 receptors in the frontal cortex in vivo; binding in the striatum was unaffected by the LSD antagonists. However, in doses which produce the LSD cue, neither LSD nor the 5-HT agonist, 5-methoxy-N,N dimethyltryptamine, which substitutes for LSD, inhibited the binding in either the cortex or the striatum. The results are discussed in relation to the possible neuropharmacological basis for the LSD cue. PMID- 2931090 TI - Isolation and physicochemical and functional properties of a calcium binding gluten fraction. AB - Each milligram gluten protein isolated from bread contains 0.03-0.06 mumol calcium. On theoretical grounds we have concluded that this calcium quantity is bound to the free carboxyl groups not participating in peptide bonds of dicarbonic aminoacids, especially glutaminic acid, making up a large proportion within the aminoacids of gluten. After treatment with EGTA, a well-known calcium complex forming compound, two gluten fractions can be distinguished: water soluble gluten-ES, and gluten-EP soluble in acetic acid. The aminoacid composition of gluten-ES is similar to that of unfractionated gluten. It is rich in aminodicarbonic acid (glu), aminodicarbonic acid amide (gln) and proline. Further properties of gluten-ES are: immunological similarity to gluten; a molecular mass of 36 000 dalton; an absorption maximum at 275.6 nm; a Ca2+ binding capacity of 0.72 mumol Ca2+/mg protein as measured by atomic absorption spectrophotometry and by Ca2+ ion selective electrode; inhibitory effect of a small quantity (25-30 micrograms) of the compound on the Ca2+-Mg2+ dependent ATPase and Ca2+-uptake of fragmented sarcoplasmatic reticulum. Preliminary experiments have demonstrated that gluten-ES has an influence on other calcium ion mediated systems like actomyosin superprecipitation. We put forward the hypothesis that by its Ca2+-binding capacity, gluten-ES is capable of influencing the level of free calcium and may thus play a part in the pathomechanism of coeliac disease. PMID- 2931092 TI - 'Corticosteroid therapy and the dental patient'. PMID- 2931091 TI - Erythrocyte enzyme allotypes in the X-linked recessive disorders, Duchenne muscular dystrophy and haemophilia-A hemizygotes and heterozygotes. AB - The erythrocyte enzyme-systems acid phosphatase, phosphoglucomutase, glutamate pyruvate transaminase, adenosine desaminase, adenylate kinase, glyoxase, glucose 6-phosphate dehydrogenase and esterase-D-isoenzyme phenotypes were studied for their percentile distribution and were compared with their incidence in the diseases with X-linked recessive heredity, Duchenne muscular dystrophy (DMD) and haemophilia-A, in hemizygous male children and heterozygous mothers. Considering the frequency distribution of the above mentioned isoenzyme phenotypes of the enzyme-systems in DMD, the phenotypes proved to be homogeneous, only the X transmitted 6-phosphogluconate dehydrogenase (6-PGD) isoenzyme types were found to be genetic markers in DMD hemizygotes and heterozygotes. In these genotypes the 6-PGD A phenotype showed a decrease while the phenotypes 6-PGD AB and B were significantly increased. The adenylate kinase (AK) 2-1 isoenzyme phenotype was increased to 25% against the population frequency of 6.34%, while the AK 1-1 phenotype occurred in 75% against its population frequency of 93.59%, showing a significantly decreasing tendency in haemophilia-A hemizygotes and heterozygotes. PMID- 2931094 TI - Safe anaesthetic for laparoscopy with spontaneous respiration. PMID- 2931093 TI - Balloon valvuloplasty and angioplasty in congenital heart disease. AB - Balloon dilatation valvuloplasty was performed in 16 patients with pulmonary valve stenosis aged 10 days to 17 years. Gradients were reduced in all but two patients and were less than or equal to 20 mm Hg after the procedure in all but these two and one other. Unsatisfactory initial results in these three patients were attributed to the use of too small a balloon in one patient (gradient subsequently abolished at repeat valvuloplasty), to a dysplastic valve in a neonate, and to the fact that there had been a previous surgical valvotomy with scar tissue formation in one patient. The good result was retained in six of seven patients followed up at three to six months. In one the gradient, having been reduced from 60 to 18 mm Hg, had risen to 35 mm Hg. Repeat valvuloplasty was technically impossible in this patient, but in two others residual gradients of 24 and 22 mm Hg were reduced to 4 and 8 mm Hg respectively by repeat valvuloplasty. Balloon dilatation angioplasty was successful in dilating a severe stenosis at the lower limb of an atrial baffle (previous correction of complete transposition) and in dilating supravalvar stenosis of the pulmonary artery resulting from previous banding and debanding. Thus balloon pulmonary valvuloplasty, though still a new technique, appears to be the treatment of choice in patients with typical pulmonary stenosis and thin mobile valves. Patients with dysplastic valves may be less suitable candidates for the procedure. Balloon angioplasty is likely to have other applications, including the treatment of postoperative stenotic lesions. PMID- 2931095 TI - Effect of interleukin-2 on the inhibition of the human mixed lymphocyte reaction (MLR) by azathioprine. AB - The effect of interleukin-2 on the response of the human MLR to azathioprine was studied. Azathioprine (36 microM) inhibited the MLR by 86% and interleukin-2 (25%) stimulated the MLR by 99%. Only partial relief (16%) of azathioprine (36 microM) inhibition was found in the interleukin-2 treated MLR compared with azathioprine treatment alone. However, [3H]-thymidine incorporation by azathioprine (36 microM) + interleukin-2 treated MLR was 4.3 times greater than that exposed to azathioprine alone. As the residual number of immunocompetent cells after drug exposure is pathologically more important than the fraction suppressed, this result may be of clinical relevance. These results show that the major mode of action of azathioprine is not the inhibition of interleukin-2 production. PMID- 2931096 TI - Ex vivo effects of nifedipine, nisoldipine and nitrendipine on filterability of red blood cells from healthy volunteers. AB - In a balanced, randomised and double-blind trial, the effects of single oral dose of nifedipine, nitrendipine and nisoldipine were compared with placebo in eight healthy volunteers. Red cell filterability, measured with a gravity driven filtration technique, was not significantly altered by any of the three calcium antagonists compared with placebo, when RBCs were filtered within 2 h of venepuncture. Storage of RBCs for 24 h at 25 degrees C, however, significantly reduced RBC filterability compared with 2 h (P less than 0.05), but the reduction after nifedipine and nitrendipine was significantly (P less than 0.05) less than after placebo. The above results demonstrate an effect of calcium antagonists on filterability of stored RBCs. PMID- 2931097 TI - DNA repeat length in chromatin from murine bone marrow and L1210 leukaemia cells. AB - Previous studies have suggested that 1-(4-amino-2-methylpyrimidine-5-yl)-methyl-3 (2-chloroethyl) -3-nitrosoureahydrochloride (ACNU) and 1,(2-chloroethyl)-3 cyclohexyl-1-nitrosourea (CCNU) bind specifically to the nucleosomal DNA of murine bone marrow and L1210 leukaemia cells whereas the glucose nitrosoureas, 2 (3-(2-chloroethyl)-3-nitrosoureido)-2-deoxy-D-glucopyranose, (chlorozotocin, CLZ) and 1-(2-chloroethyl)-3-(-D-glucopyranosyl)-1-nitrosourea (GANU), bind preferentially to the linker DNA of bone marrow but not tumour cell chromatin. In order to provide an explanation for this differential, the DNA repeat and linker lengths in murine bone marrow and L1210 leukaemia cells were measured using electrophoresis of micrococcal nuclease-digested DNA. The linker length of bone marrow chromatin was approximately 22% longer than that in L1210 leukaemia cells from mouse ascites. The linker length of L1210 cells maintained in suspension culture was 27% less than in those from ascites fluid. The tissue-specific toxicity of sugar nitrosoureas and the differential binding of these drugs to chromatin does not appear to correlate quantitatively with differences in DNA linker length. PMID- 2931098 TI - Lineage specific classification of leukaemia: results of the analysis of sixty cases of childhood leukaemia. AB - In addition to conventional morphological, histochemical and immunological marker studies, cells from 60 children with leukaemia were further analysed using the Southern blot hybridization technique to look at differences in the organization of immunoglobulin (Ig) genes. Of the 60 patients studied by conventional means, 47 were diagnosed as acute lymphocytic leukaemia (ALL) and 13 as non-lymphocytic leukaemia. Seven patients were initially classified as T ALL and 40 as non-T, non B ALL. Further subclassification of the 40 patients with non-T, non-B ALL indicated three pre-B ALL and 29 patients diagnosed as common ALL, expressing Ia and CALLA antigens. All 29 patients with common ALL demonstrated C mu gene rearrangements with or without light chain (kappa and lambda) genes rearrangement. Based on the developmental hierarchy of Ig gene rearrangement, it was possible to further subclassify the patients with common ALL into different stages of B cell development. Eight (of the 40) patients with non-T, non-B ALL were identified as CALLA- but further analysis indicated T-lineage origin in two patients and three patients were reclassified as acute undifferentiated leukaemia (AUL). C mu gene rearrangements were detected in two patients with T ALL, two patients with AUL and one patient with acute myelogenous leukaemia (AML). In contrast to the patients with common ALL, Ig gene rearrangement observed in these non-B-lineage cells was restricted to a single C mu gene while retaining germ line configuration of the other allele of the C mu gene and both light chain genes. PMID- 2931099 TI - The transfer of free fatty acids across the human placenta. AB - Thirty-three matched maternal venous and umbilical cord vein and artery plasma samples were obtained at elective caesarean section and the concentrations of the individual free fatty acids determined. The maternal levels were 1.009 (SEM 0.043) and the umbilical vein-artery difference was 0.036 (SEM 0.011) mmol/l. There was a significant correlation between the mean concentration in maternal venous blood and the vein-artery difference for myristic, palmitic, stearic, linoleic and docosahexaenoic acids but not for oleic acid. When arachidonic acid concentration in the fetus was high, then the vein-artery difference was negative (flow to the placenta), when it was low, the difference was positive (flow to the fetus). Thus whilst there appears in general to be a flow of fatty acid to the fetus dependent on maternal free fatty acid concentrations, the transfer of arachidonic acid is largely determined by other factors. The reasons why oleic acid does not behave like the other fatty acids is not clear. PMID- 2931100 TI - Langerhans' cells and lymphocyte subsets in the female genital tract. AB - Cryostat sections of healthy cervical, vaginal and vulval epithelium were examined using immunohistological labelling techniques and a panel of monoclonal antibodies recognizing Langerhans' cells, T- and B-lymphocytes and HLA-DR antigen. The distribution of Langerhans' cells in squamous epithelium of the cervix, vagina and vulva showed a marked variation with the highest median values in the vulva (18.7 per 100 basal squamous cells) and the lowest in the vagina (5.5 per 100 basal squamous cells). There was also a substantial variation in number and distribution of lymphocytes of each of these three areas with a distinct preponderance in the transformation zone of the cervix. In addition, intraepithelial lymphocytes, predominantly of the T-cytotoxic suppressor sub-type were present at all sites with the greatest number in the transformation zone. We conclude from this study that lymphoid tissue of the cervical transformation zone has several unique characteristics which are not observed at other sites in the lower genital tract. We suggest that this tissue be designated 'cervical lymphoid tissue' and that it forms a part of the 'mucosal associated lymphoid tissue' (MALT) as noted at other mucosal sites exposed to the external environment. PMID- 2931101 TI - Oro-facial granulomatosis: a possible allergic basis. AB - Food or flavouring intolerance has been demonstrated in 14 out of 80 patients with oro-facial granulomatosis. Provoking molecules include cinnamaldehyde, carvone and piperitone, although a wide range of food or flavourings may be implicated. The nature of the reaction is not understood but does not seem to involve an IgE mediated response. At present the only reliable way of detecting specific provoking factors is by the use of an elimination diet. PMID- 2931102 TI - Sarcoidosis of the tongue--a case report. AB - A case of sarcoidosis, unusual in that it was confined to the tongue, is reported in a 50 year-old female. The condition resolved after 1 year of steroid therapy and excision of fibrous tethering bands. Intra-oral sarcoidosis should be considered in the differential diagnosis of lingual swelling and induration. PMID- 2931103 TI - Pyoderma gangrenosum with involvement of the tongue. PMID- 2931104 TI - The submucosal island flap in the closure of oro-antral fistula. AB - A submucosal island palatal flap technique was used successfully in seven patients for closure of large oro-antral fistulae. The technique provides not only an island flap of submucosal connective tissue to close the fistula, but a flap of mucosa to cover the raw area of palatal bone. The advantages of the technique are that healing is satisfactory without denuded bone, the island flap has excellent mobility and does not produce bunching of the mucosa of the hard palate and recipient site, and dentures may be fitted early following the excellent healing of the wound. PMID- 2931105 TI - Palatal fistula due to an electrical burn. PMID- 2931106 TI - Subluxation of the atlanto-axial joint. AB - A case of post operative atlanto-axial dislocation is presented which was diagnosed on CT scan although the clinical signs and symptoms should have suggested the diagnosis. It is recommended that all patients who present with torticollis in the early post operative period should be considered to have C1-C2 dislocation and an orthopaedic opinion should be sought. PMID- 2931107 TI - Fracture of the cervical spine complicating bilateral fractures of the mandible: a case report. AB - A case reported of a 21-year-old male who sustained a fracture of the body of the second cervical vertebra, a bilateral fracture of the mandible and a deep laceration on the left side of his neck. The importance of excluding cervical spine fractures in cases of severe trauma to the head and neck is emphasised, and the airway management problems are discussed. PMID- 2931108 TI - Rhabdomyoma of the floor of the mouth: a new case and review of recently reported intra-oral rhabdomyomas. AB - Extra-cardiac rhabdomyoma is a rare, benign neoplasm of skeletal muscle origin which occurs predominantly in the head and neck region, mainly in the oral cavity. This article reports a rhabdomyoma (adult type) in the floor of the mouth in a 39 year-old man. The detailed histological features are presented and recent cases from the literature are reviewed. PMID- 2931109 TI - A case of branchial (lympho-epithelial) cyst, illustrating the value of ultrasound in diagnosis of cervical swellings. AB - Ultrasound has until recently found little application in oral and maxillofacial surgery despite wide use in other specialties. Ultrasound imaging uses the reflection of pulses of high frequency sound to display soft tissues and to differentiate between tissue types, particularly solid and cystic. A case of branchial (lymphoepithelial) cyst is presented to illustrate the use of ultrasound, and the aetiology and histogenesis of this controversial lesion is discussed. Ultrasound as a safe, painless, non-invasive technique is recommended as an additional investigation for neck swellings, particularly in view of the high incidence of malignancy claimed to occur in this region. PMID- 2931110 TI - Occult multiple myeloma associated with amyloid of the tongue. AB - A patient developed painless swellings of the tongue which proved to be due to amyloid. An initial search for multiple myeloma was negative; however, three months later Bence-Jones proteinuria developed and multiple myeloma was diagnosed. PMID- 2931111 TI - A new frame for cranio-maxillary fixation. AB - This paper describes a modified frame for external fixation of fractured maxillae using supra-orbital pins. PMID- 2931112 TI - Fourier-transform infrared studies of CaATPase partitioning in phospholipid mixtures of 1,2-dipalmitoylphosphatidylcholine-d62 with 1-palmitoyl-2 oleoylphosphatidylethanolamine and 1-stearoyl-2-oleoylphosphatidylcholine. AB - CaATPase from rabbit sarcoplasmic reticulum has been reconstituted into binary lipid mixtures of 1-palmitoyl-2-oleoylphosphatidylethanolamine (POPE)/1,2 dipalmitoylphosphatidylcholine-d62 (DPPC-d62) and 1-stearoyl-2 oleoylphosphatidylcholine (SOPC)/DPPC-d62. Fourier-transform infrared (FT-IR) spectroscopy has been used to monitor temperature-induced structural alterations in the individual lipid components in the presence and absence of protein. A simple two-state model is used to construct a phase diagram that is in good agreement with one constructed from differential scanning calorimetry data, for the POPE/DPPC-d62 (protein-free) system. Although these two lipids are miscible over at least most of the composition range, substantial deviations from ideal behavior are observed. An estimate of the nonideality of mixing in both the gel and liquid-crystalline phases is obtained from regular solution theory. The phase diagram for SOPC/DPPC-d62 shows gel-phase immiscibility. FT-IR studies of ternary (POPE/DPPC-d62/CaATPase) complexes indicate that both lipid components are disordered by protein at all temperatures studied. In addition, their melting events are broadened and shifted to lower temperatures compared with the appropriate binary lipid mixture. Semiquantitative estimates for the fraction of each lipid melted are obtained from the model. The effect of protein on SOPC/DPPC d62 mixtures depends on that total lipid to protein ratio. At low protein levels, SOPC is preferentially selected by CaATPase, so that bulk lipid is enriched in DPPC-d62. At high levels of protein, both lipid components are selected. The applicability of vibrational spectroscopy for determination of the partitioning preferences of membrane proteins into regions of particular chemical structure or physical order in a complex lipid environment is demonstrated. PMID- 2931113 TI - Fatty acids bound to unilamellar lipid vesicles as substrates for microsomal acyl CoA ligase. AB - Palmitate incorporated into single-layered vesicles of phosphatidylcholine was used as a substrate for palmitoyl coenzyme A ligase (palmitoyl-CoA ligase) in microsomes from rat liver. This was done in order to avoid the use of detergents for dispersal of the water-insoluble palmitate and the possibility of precipitating palmitate added to the aqueous assay as a salt suspension. The activity of the ligase measured when palmitate was added to assays as a component of phospholipid vesicles was 10-40-fold greater vs. activities reported in the literature using other methods for adding fatty acids to the assay system. Phospholipids, however, had no direct effect on the activity of palmitoyl-CoA ligase. The data indicate, therefore, that the activity of this enzyme has been underestimated because of the manner in which fatty acid was added to the assay, which has a significant effect on the activity of the ligase. It is shown too that the rate of spontaneous transfer of palmitate from unilamellar vesicles of phosphatidylcholine to microsomes via a hydrated intermediate is far more rapid than the inherent catalytic activity of the fatty acyl-CoA ligase. The data also suggest that the membrane-associated pool of fatty acid and not fatty acid in the aqueous phase of the assay is the pool of substrate interacting with the ligase. PMID- 2931114 TI - Transient kinetics of adenosine 5'-triphosphate hydrolysis by covalently cross linked actomyosin complex in water and 40% ethylene glycol by the rapid flow quench method. AB - The initial steps of the ATPase of covalently cross-linked actomyosin subfragment 1 (acto-SF-1) were studied by the rapid flow quench method, and the results obtained were compared with those with reversible (i.e., non-cross-linked) acto SF-1 and SF-1 under identical conditions. Cross-linked acto-SF-1 plus [gamma 32P]ATP reaction mixture milliseconds old was quenched either in a large excess of unlabeled ATP (ATP chase) or in acid (Pi burst). The conditions were pH 8 and 15 degrees C at 5 mM or 0.15 M KCl and with or without 40% ethylene glycol. In 40% ethylene glycol (5 mM KCl), as with SF-1 and reversible acto-SF-1, the ATP chase was used to titrate active sites and to study the kinetics of ATP binding. Unlike those with SF-1 or reversible acto-SF-1, saturation kinetics were not obtained. The second-order rate constant for ATP binding was 3.1 X 10(6) M-1 s-1 for cross-linked acto-SF-1, 1.8 X 10(6) M-1 s-1 for reversible acto-SF-1, and 2 X 10(6) M-1 s-1 for SF-1. In Pi burst experiments, a transient phase could not be discerned. Because of a high kcat, cross-linked acto-SF-1 was difficult to study in aqueous solution, but at 5 mM KCl, the ATP chase and Pi burst curves were similar to those obtained in 40% ethylene glycol. At 0.15 M KCl the ATP chase curve was difficult to interpret (small amplitude), and there was a small Pi burst.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2931115 TI - The nature of the Ca2+-pump defect in the red blood cells of patients with cystic fibrosis. AB - The reduction in (Ca2+ + Mg2+)-ATPase activity in the cystic fibrosis red blood cells can be attributed to a reduction in the number of active Ca2+ pumps per red blood cell and an altered interaction of calcium ions with the pump. Despite this, the normal free intracellular [Ca2+] is preserved due to a lower rate of passive calcium entry. PMID- 2931116 TI - Subcellular origin of the oxalate- or inorganic phosphate-stimulated Ca2+ transport by smooth muscle microsomes: revisitation of the old problem by a new approach using saponin. AB - Saponin, a cell-skinning reagent which perforates the cell membrane via its specific interaction with plasmalemmal cholesterol, was used to identify the subcellular origin of ATP-dependent Ca2+ accumulation in the presence and absence of inorganic phosphate and oxalate by microsomal fractions isolated from rat vas deferens and dog aorta. The purified plasma membranes from rat gastric fundus muscle, which elicit the stimulation of ATP-dependent Ca2+ accumulation by inorganic phosphate but not by oxalate, were used as a control reference. Saponin at concentrations effective for skinning smooth muscle fibres (10-50 micrograms/ml) inhibited Ca2+ binding in the absence of ATP to a similar extent in all fractions, but the inhibition of ATP-dependent Ca2+ accumulation was more pronounced in dog aorta microsomes and rat gastric fundus muscle plasma membranes than in rat vas deferens microsomes. The resistance of phosphate- and oxalate stimulated ATP-dependent Ca2+ accumulation to inhibition by saponin was much greater in rat vas deferens than in dog aorta microsomes. Our results suggest that phosphate- and oxalate-stimulated ATP-dependent Ca2+ accumulation also occurs in plasma membrane vesicles isolated from smooth muscle and is by no means an unique property of endoplasmic reticulum. PMID- 2931118 TI - Stimulation of bovine milk galactosyltransferase activity by bovine colostrum N acetylglucosaminyltransferase I. AB - Purified bovine milk galactosyltransferase was stimulated by purified bovine colostrum N-acetylglucosaminyltransferase I by more than 10-fold. Only slight stimulation of the N-acetylglucosaminyltransferase I by galactosyltransferase was observed. Heat inactivation destroyed the ability of the N acetylglucosaminyltransferase I to stimulate the galactosyltransferase. The stimulation of galactosyltransferase was accompanied by a decrease in Km of this enzyme from 9.7 to 3.3. mM and an increase in Vmax from 1.87 to 3.71 nmol galactose transferred/min per mg galactosyltransferase when GlcNAc was the substrate. When the Km for UDPgalactose was determined, it increased from 0.19 to 0.42 mM in the presence of N-acetylglucosaminyltransferase I and the Vmax increased from 0.66 to 2.76 nmol galactose transferred/min per mg galactosyltransferase. In phosphatidylcholine vesicles, no effect on Km values with GlcNAc as substrate was noted, while an increase in the Km of UDPgalactose was observed. The Vmax values were generally higher in the lipid vesicles. Complex formation between galactosyltransferase and N acetylglucosaminyltransferase I was demonstrated both by glycerol density gradient centrifugation and Bio-Gel P-100 column chromatography. An approximate molecular weight for the complex was obtained on a calibrated Sephadex G-200 column and found to be about 75 000, consistent with a 1:1 complex. The stimulation of galactosyltransferase involved the N-acetyllactosamine synthetase activity of this enzyme and not the lactose synthetase activity, since the latter activity was only slightly affected. Since N-acetylglucosaminyltransferase I is not involved in the lactose synthetase reaction, the stimulation is consistent with the known biosynthetic role of N-acetylglucosaminyltransferase I in the biosynthesis of asparagine-linked oligosaccharides. PMID- 2931117 TI - Stoichiometric and electrostatic characterization of calcium binding to native and lipid-substituted adenosinetriphosphatase of sarcoplasmic reticulum. AB - The stoichiometry of calcium binding to specific sites (i.e., those producing enzyme activation) was found to be 8-10 nmol/mg protein in native sarcoplasmic reticulum vesicles, and 13.9-15.4 nmol/mg of ATPase purified by non-ionic detergent solubilization and anion exchange chromatography. Parallel measurements of phosphoenzyme yielded levels of 4.0-4.9 and 6.0-7.7 nmol/mg of protein in the two preparations, respectively, demonstrating that each 115 kDa ATPase chain includes one catalytic site and two calcium binding sites. The apparent association constant, K = (6 +/- 2) X 10(5) M-1, and the binding cooperativity, nH = 1.9, were unchanged when measurements were carried out with native sarcoplasmic reticulum vesicles and when the membrane surface charge was altered by lipid substitution with phosphatidylcholine or phosphatidylserine, at neutral pH in the presence of 10 mM MgCl2 and 80 mM KCl. On the other hand, the apparent association constant was increased in the absence of Mg2+ or, to a lesser extent, in the absence of monovalent cations. It was also observed that the cooperative character of the calcium binding isotherms was reduced in low ionic-strength media. Analysis of the electrostatic effects indicates that the calcium-binding domain is shielded from the membrane phospholipid surface charge by virtue of its location within the ATPase protein. The effects of various electrolytes are attributed to monovalent-cation binding in the calcium-binding domain. The apparent loss of cooperativity of the calcium binding isotherms at low ionic strength is attributed to a progressive displacement of the titration curve which is minimal at low degrees of saturation and becomes larger at higher degrees of saturation. This behavior is described quantitatively by the progressive effect of calcium binding on an electrostatic potential generated by localized protein charge densities within, or near, the calcium-binding domain. PMID- 2931119 TI - Inhibition of phosphoglucomutase by fructose 2,6-bisphosphate. AB - Fructose 2,6-bisphosphate inhibits phosphoglucomutase. The inhibition is mixed with respect to glucose 1,6-bisphosphate and non-competitive with respect to glucose 1-phosphate. In contrast with fructose 1,6-bisphosphate and glycerate 1,3 bisphosphate, which also possess inhibitory effect, fructose 2,6-bisphosphate does not phosphorylate phosphoglucomutase. Fructose 2,6-bisphosphate preparations contain contaminants which can explain artefactual results previously reported. PMID- 2931120 TI - Effect of calcium on protein composition of human platelet cytoskeletons. AB - Triton X-100 residues (cytoskeletons) of human platelets were prepared in the presence of various concentrations of free calcium (Ca2+), and the polypeptide composition and ATPase activity were examined. Triton residues prepared in the presence of Ca2+ concentrations below 2 X 10(-7) M were composed primarily of polypeptides with an apparent molecular mass of 43 (actin), 105 (alpha-actinin like protein) and 250 (actin-binding protein) kDa and showed low K+-EDTA-ATPase activity. When Triton residues were prepared at Ca2+ above 5 X 10(-7) M, a 200 kDa polypeptide (myosin heavy chain) and K+-EDTA-ATPase activity increased markedly, but actin-binding protein and alpha-actinin-like protein decreased. When N-(N-(L-3-trans-carboxyoxirane-2-carbonyl)-L-leucyl)agmatine, an inhibitor for Ca2+-dependent proteinase, was added to Triton lysis buffer containing high Ca2+, polypeptides of 250, 235 and 105 kDa remained associated with the residues. Under electron microscopic analysis, the treatment of platelets with Triton X-100 at low Ca2+ showed a network of microfilaments. When platelets were treated with high Ca2+, the microfilaments were disrupted and a few thick filaments and many granules appeared. However, when the inhibitor for Ca2+-proteinase was included in Triton lysis buffer, the microfilaments remained intact. These results suggested that an increase in Ca2+ concentration to more than 5 X 10(-7) M not only makes myosin associate with cytoskeletons but also regulates the organization of filamentous structures. PMID- 2931121 TI - The influence of caldesmon on ATPase activity of the skeletal muscle actomyosin and bundling of actin filaments. AB - Chicken gizzard caldesmon causes up to 40% inhibition of Mg2+-ATPase activity of rabbit skeletal muscle actomyosin. In the presence of chicken gizzard tropomyosin this inhibition is significantly increased, reaching a maximum (around 80%) at a molar ratio of caldesmon to actin monomer of 1 to 10-13. The inhibition of actomyosin ATPase takes place over a wide pH range (from 6.0 to 8.0) but is decreased with an increase in KCl and MgCl2 concentrations. Caldesmon, in the range of caldesmon/ actin ratios within which it inhibits actomyosin ATPase, forms bundles of parallelly aligned actin filaments. Calmodulin in the presence of Ca2+ dissociates these bundles and restrains the inhibition of actomyosin ATPase, provided that it is used at a high molar excess over caldesmon. PMID- 2931122 TI - Mechanism of SOS-induced targeted and untargeted mutagenesis in E. coli. AB - This paper retraces the evolution of hypotheses concerning mechanisms of SOS induced mutagenesis. Moreover, it reports some recent data which support a new model for the mechanism of targeted and untargeted mutagenesis in E. coli. In summary, the SOS mutator effect, which is responsible for untargeted mutagenesis and perhaps for the misincorporation step in targeted mutagenesis, is believed to involve a fidelity function associated with DNA polymerase III and does not require the umuC gene product. umuC and umuD gene products are probably required specifically for elongation of DNA synthesis past blocking lesions, i.e. to allow mutagenic replication of damaged DNA. PMID- 2931123 TI - In vitro fertilization of bovine follicular oocytes obtained by laparoscopy. AB - Bovine follicular oocytes (n = 454), obtained after laparoscopy, were used to study in vitro capacitation, fertilization, and embryo development. Capacitation was accomplished by treating bovine spermatozoa with high ionic strength medium. Maturation, fertilization, and development studies were carried out in Brackett's defined medium or in Ham's F-10. In vitro fertilization rates, ranging from 14% to 55%, were found to be influenced by individual variations among males. Brackett's defined medium was found to be superior to Ham's F-10 for oocyte maturation, fertilization, and growth, these media giving cleavage rates of 60% and 32%, respectively. Oocytes with expanded cumuli at the time of recovery cleaved at a rate of 43%, which is significantly different from oocytes recovered without granulosa cells (22%) or oocytes with compact cumuli and corona cells (5%). The in vitro development pattern of the in vitro-fertilized embryos was found to be similar to that observed in vivo. Embryos were observed at the 2-cell stage 44.5 +/- 6.3 h after in vitro insemination, 4-cell after 59.0 +/- 9.4 h, 8 cell after 74.8 +/- 12.7 h, and 16-cell after 96.2 +/- 13.9 h (observations at 12 h intervals). The procedures described here resulted in cleavage rates of up to 60% using follicular oocytes embedded in expanded cumuli cells and semen samples from selected males. PMID- 2931124 TI - Gas chromatography/mass spectrometry of bacterial amines. AB - Bacterial amines were examined by gas chromatography/mass spectrometry. Under electron impact all trifluoroacetamides exhibited peaks at m/z 69 due to [CF3]+. Many trifluoroacetamides also showed peaks at m/z 97 corresponding to the [COCF3]+ ion fragment. The spectra of n-alkyl and aralkyl trifluoroacetamides were consistent with the spectra and their interpretations in the earlier literature. Molecular ions were of low abundance for all alkyl trifluoroacetamides having alkyl chains longer than two carbon atoms. Chemical ionization gave molecular weight information in all cases. Most peaks observed were molecular addition products, e.g. [M + H]+ and [M + NH4]+. Application of chemical ionization mass spectrometry to analysis of bacterial amines revealed the production of beta-phenylethylamine, n-decylamine, 1,4-diaminobutane and 1,5 diaminopentane by Clostridium histolyticum; whereas both Clostridium bifermentans and Clostridium oedematiens produced beta-phenylethylamine. The latter organism also produced a peak with a retention time similar to that of an authentic amylamine derivative. PMID- 2931125 TI - Derivatization of ketosteroids for fast atom bombardment mass spectrometry. AB - Girard's reagents were used to derivatize ketosteroids and conjugates for analysis by positive ion fast atom bombardment mass spectrometry. Spectra contain an abundant ion corresponding to the cation (C+) of the newly formed ionic derivative (C+A-) and relatively little fragmentation. With derivatization, detection of ketosteroids at a concentration of 1 microgram microliter-1 in glycerol was straightforward. Such derivatization schemes may prove useful in the analysis of ketosteroids in complex biological mixtures. PMID- 2931126 TI - Biotransformation of terodiline I. Identification of metabolites in dog urine by mass spectrometry. AB - Nine metabolites of terodiline (N-tert-butyl-4,4-diphenyl-2-butylamine) have been identified in dog urine by various chromatographic techniques and mass spectrometry. The main metabolic pathway is aromatic hydroxylation, leading to the quantitatively most important metabolite, N-tert-butyl-4-(4-hydroxyphenyl)-4 phenyl-2-butylamine, and to two dihydroxylated metabolites, one mono substituted in both rings (N-tert-butyl-4,4'-bis(4-hydroxyphenyl)-2-butylamine), and one disubstituted in one ring (N-tert-butyl-4-(3,4-dihydroxyphenyl)-4-phenyl-2 butylamine). The latter is further metabolized by methylation, forming N-tert butyl-4-(4-hydroxy-3-methoxyphenyl)-4-phenyl-2-butylamine, the second most abundant metabolite. Still another metabolite is formed by hydroxylation in the tert-butyl group to N-(2-hydroxymethyl-2-propyl)-4,4-diphenyl-2-butylamine. A very minor dihydroxylated metabolite results from oxidation both in an aromatic ring and in the tert-butyl group, giving N-(2-hydroxymethyl-2-propyl)-4-(4 hydroxyphenyl)-4-phenyl-2-butylamine. Oxidation of the carbon adjacent to the nitrogen and subsequent deamination gives the two ketones 4-(4-hydroxyphenyl)-4 phenyl-2-butanone and 4-(4-hydroxy-3-methoxyphenyl)-4-phenyl-2-butanone. Reduction of the carbonyl function in the former yields the corresponding alcohol, 4-(4-hydroxyphenyl)-4-phenyl-2-butanol. Some unchanged terodiline is also present. All metabolites formed by functionalization appear to be extensively conjugated, presumably with glucuronic acid. PMID- 2931127 TI - Comparison of 252californium plasma desorption and fast atom bombardment mass spectrometry for analysis of small peptides. AB - The data obtained with 252Cf plasma desorption (PD) and fast atom bombardment mass spectrometry of eight tri-, tetra- and pentapeptides were compared. Good spectra were obtained with 1-10 nmol of peptide. In both techniques molecular weight information was obtained. The PD mass spectra are often dominated by the cationized molecular ions in contrast to the fast atom bombardment (FAB) mass spectra, where cationization is rarely observed. Amino acid content is reflected in the immonium ions equally well in both techniques. The fragmentation patterns observed with the two techniques are almost identical. However, practical sequencing of peptides based on either FAB or PD mass spectrometry of underivatized peptides alone is difficult. This is due to the unpredictable and sometimes absent cleavage yield at certain peptide bonds. Another difficulty is the many simultaneous fragmentation pathways. However, for many peptides enough information is present to allow sequence determination for at least a major part of the molecule. PMID- 2931128 TI - Determination of pentacaine, trans-2-(1-pyrrolidinyl)cyclohexyl-3 pentyloxycarbanilate hydrochloride, in biological samples by gas chromatography/mass spectrometry. AB - A quantitative and selective method has been developed for the determination of a novel local anaesthetic compound pentacaine, trans-2-(1-pyrrolidinyl)cyclohexyl-3 pentyloxycarbanilate hydrochloride, in biological samples. After ion pair extraction from 1 M HCl into 1,2-dichloroethane, pentacaine and a structurally related internal standard were derivatized to prevent thermal decomposition in the gas chromatograph. An on-column methylation technique with trimethylanilinium hydroxide was used. Determination was performed by gas chromatography/mass spectrometry (GC/MS) with selected ion monitoring. Interferences by endogenous lipophilic constituents were avoided by including an n-hexane wash before the ion pair extraction. This wash step did not reduce the drug recoveries. The method gave linear results over a concentration range of 5-100 ng ml-1 with a coefficient of variation less than 10% at 5 ng pentacaine ml-1. Specimens of plasma, whole blood, urine as well as in vitro preparations such as hepatic microsomes were successfully analysed. PMID- 2931129 TI - Verification of the DNA predicted amino acid sequence of bacteriophage P22 tail protein by mass spectrometry. AB - Mass spectrometry was used to verify portions of a proposed amino acid sequence of the bacteriophage P22 tail protein which had been inferred from the DNA base sequence. The exopeptidases dipeptidyl aminopeptidase I and IV and dipeptidyl carboxypeptidase were used to hydrolyse intact protein and fragments generated by cyanogen bromide treatment of the tail protein. After partial purification by high performance liquid chromatography, peptides were identified by gas chromatography/mass spectrometry and fast atom bombardment mass spectrometry. The results indicate that the initiation amino acid, N-formylmethionine, has been removed from the N-terminal of the protein and that the protein ends at the termination codon which is 667 amino acids from the N-terminal residue. Nine regions of the protein from 13 to 42 residues in length were verified. All of the sequences checked were in the same DNA reading frame and corresponded to the proposed sequence. PMID- 2931130 TI - Simultaneous determination of 6-oxo-prostaglandin F1 alpha and 2,3-dinor-6-oxo prostaglandin F1 alpha in biological fluids by stable isotope dilution and negative ion chemical ionization mass spectrometry. AB - A stable isotope dilution assay for the simultaneous determination of two metabolites of prostacyclin (1), 6-oxo-prostaglandin F1 alpha (2a) and 2,3-dinor 6-oxo-prostaglandin F1 alpha (3a), in human seminal fluid and human urine is described. A new chemical total synthesis of deuterated internal standard, 18,18,19,19-(2H4)-2,3-dinor-6-oxo-PGF1 alpha (3b), is presented and enables specific and sensitive quantification based on negative ion chemical ionization mass spectrometry. 2a and 3a were analysed as their methoxime pentafluorobenzyl ester tris(trimethylsilyl) ether derivatives in the selected ion monitoring mode registrating the [M-181]- fragments with a detection limit for both prostanoids of 10 pg per injection. The two metabolites occur in human seminal fluid in very low concentrations (2a: 2.8 ng ml-1; 3a: 1.7 ng ml-1) and cannot contribute significantly to the urinary metabolite levels which are in the range of 108-265 ng/24 h for 3a and 124-574 ng/24 h for 2a. PMID- 2931131 TI - Electron impact induced fragmentations of the 1,4-diene analogues of steroid hormones and related steroids. AB - The electron impact induced fragmentations observed in the mass spectra of eight 1,4-diene-3-ketopregnane steroids are described. The effect of hydroxyl substituents in positions 11 beta, 17 alpha and 21, on the typical fragmentation pattern is analysed; in particular the 'long range' effect of the 17 alpha hydroxy group on the relative abundance of the ions m/z 121 and 122 is confirmed using specific deuterium labelling. PMID- 2931132 TI - Identification of felodipine metabolites in rat urine. AB - After intragastric administration of 100 mumol kg-1 [14C]felodipine to rats eight urinary metabolites were isolated. Batch extraction at pH 2.2 and semipreparative reversed-phase liquid chromatography were used for trace enrichment of the metabolites. Trimethylsilylation followed by transesterification with diazomethane blocked the carboxylic acid and alcohol groups selectively before gas chromatography/mass spectrometry (GC/MS) in the electron impact (EI) mode. Deuterated derivatives of the metabolites and chemical ionization measurements added complementary structural information. All metabolites reported in this study were formed from oxidized felodipine by ester hydrolysis. Hydroxylation of the pyridine methyl group represented an important metabolic pathway and metabolites oxidized to the corresponding carboxylic acids were detected as well. Lactone formation from hydroxy acid metabolites in urine as a possible analytical artefact is discussed. PMID- 2931133 TI - Laser desorption Fourier transform mass spectra of malto-oligosaccharides. AB - Laser desorption mass spectra of malto-oligomers, including starch, have been obtained using Fourier transform mass spectrometry. Fragmentations of these oligomers have been examined after doping with metal salts to obtain cation attachment ions. Doping starch with NaCl, KBr and Ag2O results in analogous cation-attachment oligosaccharide fragment ions for all three metal ions. A distinct and unusual fragmentation pattern is observed for the larger oligomers. PMID- 2931134 TI - Determination of infused (13C)progesterone in ovarian arterial blood by selected ion monitoring. AB - Gas chromatography mass spectrometry (GC/MS) with selected ion monitoring (SIM) is employed to detect and approximate the levels of (13C)progesterone is small blood samples obtained at intervals from ipsilateral and contralateral ovarian arteries and a peripheral vein before, during and after infusion into the utero ovarian vein (five women during hysterectomy). The internal standard was 16 alpha methylprogesterone. The method is rapid and allows the time course of the infused hormone to be plotted in spite of large and rapidly fluctuating concentrations of endogenous progesterone. The results show for the first time the local in vivo transfer of a steroid hormone from the uterine vein to the adjacent ovary in humans. PMID- 2931135 TI - Analysis of (1-13C)leucine and (13C)KIC in plasma by capillary gas chromatography/mass spectrometry in protein turnover studies. AB - The methods used for the determination of the concentration and isotope enrichment of (1-13C)leucine and its metabolite (13C) alpha-ketoisocaproic acid (KIC) in plasma for the study of whole-body protein turnover are described. Leucine was analysed as its N-heptafluorobutyryl isobutyl ester and KIC as its quinoxalinol-TMS derivative, both by chemical ionization selected ion monitoring gas chromatography/mass spectrometry (GC/MS). The sensitivity of the leucine assay was improved 30 times by monitoring the negative ions under the conditions described. The coefficient of variation for enrichment and concentration measurements were 0.5% and 2%, respectively, with a minimum detectable enrichment of 0.1 at% excess for both assays. PMID- 2931136 TI - Erythrocyte membrane Ca2+-pumping ATPase of hypertensive humans: reduced stimulation by calmodulin. AB - The Ca2+-pumping ATPase of erythrocyte plasma membranes of hypertensive humans (HTN) show, in the absence of calmodulin, a low Vmax comparable to that of the enzyme of the erythrocyte membranes of normotensive humans (NTN). Although the addition of calmodulin (1.5 micrograms per ml) increased the maximum activity of the calcium pump of membranes of HTN and NTN individuals by at least 2-fold and 4 fold, respectively, the activator protein partially purified from the erythrocytes of HTN individuals enhanced the activity of the enzyme in a fashion similar to that of the protein obtained from the haemolysate of NTN individuals. A determination of the dependence of the activity of the pump on concentration of ATP revealed that the Km (ATP) of the enzyme of membranes of HTN individuals is 52% higher than that of the enzyme of membranes of NTN individuals, while the Vmax (1.75 +/- 0.28 mumol ATP mg protein-1 h-1) of the pump is 46% lower in the membranes of HTN humans than that of the enzyme of membranes of normal individuals (3.25 +/- 0.42 mumol ATP mg protein-1 h-1). It seems likely from these results that elevated erythrocyte Ca2+ concentration associated with essential hypertension may be due to a defective interaction between the Ca2+ pumping ATPase and the calmodulin Ca2+ complex. PMID- 2931137 TI - Crystallization of Ca2+ ATPase in sarcoplasmic reticulum vesicles by phospholipase treatment. AB - Ca2+ ATPase molecules in sarcoplasmic reticulum, isolated from rabbit skeletal muscle, have been induced to crystallize into two-dimensional arrays by incubating the vesicles with phospholipase A2 and dialysing against dilute Tris/HCl buffer. These crystals differ in shape and size from those produced by treatment of the sarcoplasmic reticulum vesicles with Na3VO4. However, the unit cell dimensions of both types of crystals are similar. The differences in shape and size are presumably due to differences in the mechanisms of crystal formation induced by treatment with phospholipase and Na3VO4. PMID- 2931138 TI - The effect of syndrome diagnosis on speech remediation. AB - On the basis of work reported by colleagues, as well as our own clinical research studies of patients with the aforementioned syndromes, there are now some useful guidelines for appropriate remediation based on accurate initial diagnosis. Still, there is more to be learned about each of these syndromes. Furthermore, they represent but a small sample of a very large total. Recent literature has described the speech patterns of many more syndromes, as well as the genetic aspects of the more common speech and language disorders such as language delay, dyslexia, autism, and stuttering [72-78]. The most common recognizable birth defect is Down syndrome and there is, fortunately, a large body of information detailing the varied language, speech, and hearing aspects [79]. Those of us who work with children with Down syndrome have been alerted to the anticipated receptive and expressive language delays; the conductive and sometimes mixed hearing losses; the hoarse and raucous voices that are probably the result of a combination of anatomic, neurologic, and mucosal variations; the interesting disfluencies, and the amalgam of developmental and deviant articulatory errors. We know that although the tongue protrudes, it is rarely the true macroglossia which we would find in Beckwith syndrome, for example, but rather a hypotonic posture and a logical adaptation to an airway restricted by enlarged tonsils and adenoids and recurrent rhinitis. PMID- 2931139 TI - A new rheological method to measure fluidity change of blood during coagulation : application to in vitro evaluation of anticoagulability of artificial materials. AB - In order to attempt in vitro evaluation of antithrombogenecity for materials of artificial blood vessel tube, a new type of rheometer was developed. The rheometer originally consists of a cylindrical tube suspended from a torsion wire and filled with blood. The tube is excited in torsional oscillation and subsequent damped oscillation is observed. The apparatus can sensitively follow the change of fluidity during coagulation of blood. The damped oscillation curves during coagulation for fibrinogen - thrombin solution and blood put in a cylindrical tube made of the artificial material were measured. For fibrinogen - thrombin solution with lower fibrinogen and thrombin concentrations, the values of logarithmic damping factor (LDF) during coagulation increased and then decreased through a maximum. For blood and fibrinogen-thrombin solution with the higher concentrations of fibrinogen and thrombin, LDF monotonously decreased with the progress of coagulation. With a glass tube, the decrease of LDF for whole blood taken without anticoagulant rapidly occurred within about 15 min after sampling, while, with expanded polytetrafluoroethylene (EPTFE; Goar tex) and polydimethylsiloxane (Silastic) tubes, the decrease of LDF proceeds over 40-60 min. The present method is probably available for in vitro evaluation of anticoagulability or antithrombogenecity of artificial materials. PMID- 2931140 TI - [Blood supply to the heart and coronary vasodilation reserves in experimental myocardial hypertrophy]. AB - The effects of pressure overload left ventricular hypertrophy (LVH) on heart performance and coronary circulation were investigated in dog experiments. The data obtained clearly demonstrate that left ventricular systolic and end diastolic pressures were increased in LVH dogs. The heart rate and cardiac output were unchanged. However, there was a tendency toward lowering in the maximal rate of myocardial contractility and relaxation (+dP/dtmax and--dP/dtmax). It has been shown that in LVH dogs, the coronary blood flow was higher and coronary artery resistance was lower than in control ones. The peak reactive hyperemic flow was higher in LVH dogs but the coronary artery resistance calculated at the height of reactive hyperemia was similar both in control and LVH dogs, evidence of a reduction in the total coronary vasodilator reserves in the latter ones. The diastolic pressure-time index-tension time index (DPTI/TTI) ratio in LVH dogs decreased so that the value was sufficiently low to predict a reduction in endocardial perfusion even in experimental increased coronary perfusion pressure. PMID- 2931141 TI - [Nature of the chalone fraction of erythrocyte extracts]. AB - The chalone fraction of erythrocyte extracts is immunologically identical to albumin and not identical to hemoglobin. It differs from albumin and hemoglobin in biological properties and electrophoretic mobility. The immune antichalone serum permits evaluating erythropoiesis in posttransfusion polycythemia and acute blood loss. PMID- 2931142 TI - Monoclonal antibodies to the 140,000 mol wt glycoprotein of B lymphocyte membranes (CR2 receptor) initiates proliferation of B cells in vitro. AB - Several mouse monoclonal IgG antibodies (AB1, AB2, AB3, and AB5) were developed that reacted with a 140,000 mol wt glycoprotein on the surface of cultured RAJI B lymphoid cells. The antibodies reacted with purified normal human peripheral blood B cells and CLL Ig+ B cells and showed specific germinal center and mantle zone staining in tissue sections of secondary lymphoid organs. Immunodepletion studies using 125I surface-labeled Raji cell membrane antigens demonstrated that the antigen identified by AB5 is the same 140,000 mol wt glycoprotein detected by anti-B2 that has recently been shown to react with the C3d fragment or CR2 receptor. (Iida et al: J Exp Med 158:1021, 1983). Addition of the AB series and anti-B2 monoclonal antibodies to cultures of purified human peripheral blood B cells resulted in the uptake of 3H-thymidine at two to six times background control levels provided that irradiated autologous T cells were added to the culture. Stimulation was not evoked by other monoclonal antibodies to B cell surface molecules (ie, B1, BA-1, BA-2, and HLA-DR). Pepsin-generated F(ab')2 fragments of anti-CR2 antibodies were essentially as effective as the intact IgG molecule in stimulating B cells. Induction of B cell proliferation by antibody binding to CR2 suggests that the C3d receptor may have an integral role in regulation of humoral immune response. PMID- 2931143 TI - Differences in T cell subsets between men and women with idiopathic thrombocytopenic purpura. AB - Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder, occurring predominantly in women. We studied by flow cytofluorimetry the T cell subsets in men and women with ITP and compared them with healthy sex-matched volunteers. In healthy controls, women were found to have higher proportions of T helper/inducer (Th/i) and lower T suppressor/cytotoxic (Ts/c) lymphocytes and consequently higher Th/i:Ts/c ratios than men. Accordingly, in clinical surveys, patients and controls should be matched for sex for proper comparisons. In patients with ITP in its active phase, an imbalance in T cell subsets was found in both sexes. The perturbation was more severe in women who had a marked decrease in number and proportion of Th/i lymphocytes and an increase in the proportion of Ts/c lymphocytes, whereas in men only, the proportion of Th/i lymphocytes was decreased. When patients with active disease were compared to those with ITP in remission, the decrease in Th/i subsets still persisted in both sexes but the Ts/c subset in women had returned to normal proportions. Therefore, the immune imbalance in ITP is more marked in women than men; imbalances in both Th/i and Ts/c are present in women while Ts/c appears not to be involved in men. PMID- 2931144 TI - A longitudinal immunologic evaluation of hemophiliac patients. AB - Over an average span of one year, we performed a prospective clinical and immunologic evaluation of 30 patients with hemophilia. No patient developed life threatening opportunistic infection or malignancy; however, the immunologic abnormalities and lymphadenopathy initially present in nine patients (lymphadenopathy group) persisted. In addition, five patients, representing 24% of the initial group without lymphadenopathy, developed generalized lymphadenopathy (converter group). One episode of idiopathic thrombocytopenia (ITP) and one episode of staphylococcal sepsis occurred in this "converter" group; one episode of ITP also occurred in the lymphadenopathy group. Sixteen patients remained asymptomatic. At the time of the follow-up evaluation, those differences in mononuclear cell (MNC) percentages and numbers noted initially among the three hemophiliac groups were no longer present. Natural killer cell function alone or in the presence of biologic response modifiers was not different among hemophiliac and control groups. Before developing lymphadenopathy, the converter group of patients had significantly better lymphocyte mitogenic function than did the other two groups of patients with hemophilia. However, lymphocyte mitogenic responses of all groups of patients with hemophilia significantly deteriorated over the course of the study. The abnormal mitogenic responses noted in these patients was explained in part by higher levels of spontaneous suppressor cell activity in mononuclear cell preparations from patients with hemophilia. We conclude that long-term immunologic studies of this patient population requires both quantitative and qualitative evaluations. Our data show that patients with hemophilia have progressive dysfunction of cell-mediated immunity. PMID- 2931145 TI - Is there an assault syndrome? PMID- 2931146 TI - The Mental-Mental Muddle and Work Comp in Oregon. II. AB - To summarize, in the state of Oregon at this time, mental illness caused by employment is covered by workers' compensation insurance. There have recently been some legislative attempts to seriously restrict this and there probably will be some more in the future. As the law now stands, the job stress must be the major contributing cause as measured against any off the job stress. The on the job events producing the stress must exist in reality. A stress emanating primarily from a worker's misperception or paranoid thinking does not constitute an acceptable causative agent. Obviously it is not always that easy to distinguish between on the job causes and off the job causes and objective stresses and merely perceived stresses. And what about the individual who has faulty perceptions which lead to actions that provoke an objective response? As a psychiatrist, I am glad to see more recognition given to mental illness caused by the work place. I applaud the Oregon Supreme Court for pointing out that an organization has an obligation to somehow deal with stress-producing supervisors. I think we have to be on guard against those forces working through the legislature which try to minimize or deny the importance of mental illness. At the same time, though, we have to try to enlighten rather than confuse. Our expertise is in diagnosing and treating, not in constructing legal terminology. In my evaluation of the Leary case, I tried to explain to the best of my ability just what was going on.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2931147 TI - Factors influencing grape worker susceptibility to skin rashes. PMID- 2931149 TI - Backache. PMID- 2931148 TI - Validity of air-helium DVmax measurements in trials of bronchodilators. AB - The authors studied the intraindividual variability of DVmax50 He-air in a large homogeneous group of 57 young healthy subjects. They found a 95% confidence interval for a true change between two repeated measurements of DVmax50 of +/- 28%. They compared the discriminant power of FEV1, Vmax50 and DVmax50 in 27 asthmatic young males and 12 normal controls, challenged on different days with fenoterol and ipratropium bromide aerosols given in random order under standardized conditions. FEV1 was not able to discriminate between the effect of the drugs in the normals or asthmatics. Vmax50 increased significantly more after fenoterol than after ipratropium in the asthmatics. DVmax50 was sometimes increased after fenoterol in the asthmatics but not by ipratropium in this group. These results suggest that sympathomimetics are more active on peripheral airways than the antimuscarinics. PMID- 2931150 TI - Experimental wound healing: increased breaking strength and collagen synthetic activity in abdominal fascial wounds healing with secondary closure of the skin. AB - Delayed primary closure or secondary closure of skin and subcutaneous fat in contaminated laparotomy incisions virtually eliminates the risk of wound abscess in clinical practice. Incisional hernias rarely develop in these wounds. This experimental study offers a possible explanation. Longitudinal incisions in the linea alba of female Wistar rats healed under skin incisions which were either sutured ('closed' subgroup) or left to close by secondary intention ('open' subgroup). Postoperative breaking strengths and collagen contents (measured as hydroxyproline) were studied at intervals of 3-120 days. Measurable strength developed by 5 days, at which time 'open' subgroup wounds were found to be weaker and to have less collagen. At all other times, however, 'open' subgroup wounds were stronger, a property which could be ascribed at earlier, but not at later, periods (42 or 120 days), to a higher content and concentration of collagen. At 3 days the rate of collagen production was significantly (P less than 0.025) lower in 'open' than in 'closed' subgroup wounds but the converse was true at 6 and 9 days (P less than 0.025), thus accounting for the changes in biomechanical properties. It is suggested that initially the stimulus for collagen synthesis is greater in the 'open' wounds and this leads to the development of a collagenous structure which is better adapted to resist tensile forces. PMID- 2931152 TI - Somatic component to myocardial infarction. PMID- 2931151 TI - Plasma testosterone concentrations in asthmatic men treated with glucocorticoids. PMID- 2931153 TI - Clinical trial of common treatments for low back pain in family practice. AB - The results of a multicentered randomised clinical trial are reported of bed rest and of a physiotherapy and education programme for patients who presented in family practice with an acute episode of low back pain. No beneficial effect of either treatment was observed on several clinical outcome measures, including straight leg raising, lumbar flexion, activities of daily living, and pain. In fact the results favoured early mobilisation over bed rest and suggested that the physiotherapy and education programme was doing more harm than good. Moreover, additional analyses, which focused on clinically interesting patient subgroups, discovered no subset of patients who benefited from either of the treatments under study. Having failed to identify any clinically important benefits, or other explanations for these negative results, we can only conclude that family doctors have little reason to prescribe either bed rest or isometric exercises to patients who suffer from low back pain. PMID- 2931154 TI - Laparoscopic diagnosis of ascites. PMID- 2931155 TI - Effect of growth hormone-releasing stimuli in streptozotocin diabetic rats. AB - The dynamics of growth hormone (GH) secretion in response to different GH secretagogues has been studied in adult freely moving male rats one month after induction of diabetes by single i.v. injection of streptozotocin (60 mg/kg). Baseline plasma GH concentrations and pituitary GH content were not different in streptozotocin-diabetic (St-D) rats and controls. Clonidine (0.15 mg/kg i.v.), an alpha 2-adrenergic agonist, failed to evoke GH release in St-D rats. Substitution therapy with insulin (1 IU/100 g b.wt.daily) delivered through subcutaneously implanted minipumps, allowed re-institution of a normal GH responsiveness to clonidine. At odds with clonidine, FK 33-824 (0.1 mg/kg i.v.), a potent analog of the opioid peptide Met-enkephalin, induced a similar rise in plasma GH levels in control and St-D rats. Finally, administration of a synthetic replicate of a GH releasing hormone of human pancreatic origin, hpGRF-40 (2.5 micrograms/kg i.v.) elicited a higher GH response in St-D rats than in controls. These data indicate that in St-D rats: (1) an impaired function of noradrenergic pathways controlling GH release is present; (2) contrary to previous beliefs, an alpha 2-adrenergic mechanism is not involved in the GH-releasing effect of opioid peptides; and (3) pituitary GH responsiveness to hpGRF is increased. PMID- 2931156 TI - Light and electron microscopic immunocytochemistry of beta-endorphin/beta-LPH like immunoreactive neurons in the arcuate nucleus and surrounding areas of the rat hypothalamus. AB - beta-Endorphin/beta-LPH-like immunoreactive neurons in the hypothalamic arcuate nucleus and its surrounding areas were visualized by light and electron microscopic immunocytochemistry. Immunoreactive processes were found in the vicinity of the pia mater, in the lateral part of the external layer of the median eminence and near the lateral wall of the third ventricle. Neuronal perikarya contained immunoreactive dense granules as well as developed cell organellae. They received neuronal inputs from other neurons through axoplasmic and axodendritic synapses. Immunoreactive neuronal processes containing dense granules and mitochondria were found as preterminal elements on non immunoreactive neuronal soma and dendrites. Immunoreactive processes also make intimate contact with capillaries in the arcuate nucleus near the median eminence. PMID- 2931157 TI - Stimulation of spinal serotonergic receptors facilitates seminal emission and suppresses penile erectile reflexes. AB - Penile erection and ejaculation are produced by spinal reflexes subject to tonic control from the brain. This study examines the possible involvement of serotonergic transmission in the supraspinal modulation of such reflexes. The effects of two drugs which facilitate serotonergic transmission by different mechanisms, namely the direct receptor agonist, 5-methoxy-N,N'-dimethyltryptamine (5-MeODMT), and the reuptake inhibitor, zimelidine, were compared in intact and spinal rats. Results show that serotonergic stimulation in intact rats by either drug produces a dose-related increase in the incidence of seminal emission as well as a definite decrease of the display of erectile responses. In the spinal animals 5-MeODMT treatment reproduced both effects. By contrast, zimelidine, which needs functional nerve endings to exert its agonistic action, was ineffective in the spinal rats. This is interpreted to exclude a peripheral mechanism for the effects of the serotonin agonists on penile reflexes of intact animals and makes a strong case for a spinal site of action. We postulate the existence of serotonergic receptors located in the lower segments of the spinal cord which, when stimulated, trigger seminal emission and suppress erection. PMID- 2931158 TI - Changes in hypothalamic dopamine D-2 receptors during sexual maturation in male and female rats. AB - We have examined variations in hypothalamic dopamine D-2 receptor levels occurring during sexual maturation in male and female rats, using a [3H]domperidone radioligand binding assay. A major decrease in D-2 receptor levels was observed during sexual development, and was accompanied by the appearance of a sexual dimorphism in receptor levels, which appeared to be the result of neonatal sexual differentiation. These changes may be linked with the alterations in hormone levels which occur during sexual maturation. PMID- 2931159 TI - [The age risk in Down's syndrome and its prevention]. PMID- 2931160 TI - The role of endorphins in septicaemic shock: a pilot study in burned patients. AB - There is recent evidence that circulating opioid peptides, or 'endorphins', act as chemical messengers responsible for the induction of the complex cardiovascular changes leading to hypotension in septicaemic shock. The pilot study of an investigation of opioid peptides in septicaemia in burned patients is presented. Serial measurements of plasma beta-endorphin and metenkephalin were performed throughout the recovery of six patients with large burns (20-70 per cent BSA). Our preliminary findings concur with previous evidence that opioid peptides may play a role in the hypotension of septicaemic shock. PMID- 2931161 TI - Medical social work in the burns unit. AB - This paper presents the social problem resolving processes in a burns unit integrated in the general hospital service in a welfare society. The social work opens possibilities of improving both patient relationships and society relationships. PMID- 2931162 TI - [Aminoglutethimide, an inhibitor of aromatase from chick embryo ovary]. AB - The gonads from 13-day-old female chick embryos were cultured in vitro on TC medium 199, and oestradiol production was measured by radioimmunoassay. In the presence of dehydroepiandrosterone as substrate, oestradiol synthesis was markedly increased, but when aminoglutethimide was also present, it was greatly reduced, depending on the concentration of the drug. This result demonstrates inhibition of the aromatizing enzyme system of the chick embryo ovary by aminoglutethimide in vitro. However, sex differentiation of the female gonads was not modified after in vivo treatment. Since it is not known whether their production is completely suppressed in vivo, the hypothesis cannot be dismissed that oestrogens play a role in ovarian differentiation. PMID- 2931164 TI - Massive haemorrhage during attempted laparoscopy. PMID- 2931163 TI - Effects of anaesthesia induction drugs on circulation in denervated intestinal loop preparation. AB - The effect of anaesthesia induction drugs on the intestinal circulation was evaluated in an isolated loop preparation in 28 dogs. Selected intestinal loops were perfused with aortic blood by a pump at a constant pressure of 100 mmHg. A mixture of 86Rb and 9 microns spheres labeled with 141Ce was injected into the arterial cannula supplying the intestinal segment while mesenteric venous blood was collected for activity counting. Diazepam in a dose of 3 mg X kg-1 was accompanied by a significantly lower clearance (Cl-Rb), and permeability-surface area product (PS) than pentobarbitone; there were no differences between diazepam and pentobarbitone in total blood flow (BF), vascular resistance (VR) and oxygen consumption in the intestinal segments. Circulatory variable observed after midazolam, 8 mg X kg-1 and an additional 16 mg X kg-1, did not significantly differ from those seen during pentobarbitone. Ketamine in a dose of 8 mg X kg-1 was accompanied by a significantly lower BF, Cl-Rb, microsphere entrapment (Cl Sph), PS, and higher VR and arterio-venous oxygen content difference. Sixteen mg X kg-1 of ketamine did not lead to any additional changes in determined variables of the intestinal circulation. Alpha-adrenoceptor blockade completely abolished vasoconstriction caused by ketamine, suggesting that the long-lasting vasoconstricting effect of ketamine on the intestinal circulation is mediated through catecholamines. PMID- 2931165 TI - Cloning of 11 alpha-tubulin gene sequences from the genome of Chinese hamster ovary cells. AB - We have analyzed the complex tubulin gene family in clonal lines of Chinese hamster ovary cells. There are approximately 16 alpha-tubulin genes and a similar multiplicity of beta-tubulin genes. The alpha-tubulin genes are not closely linked to each other nor to the beta-tubulin genes. A genomic library has been constructed in the vector lambda charon 4A containing insert sizes of 13-20 kilobases. The library has been screened with both inter- and intra-species alpha tubulin probes. Eleven alpha-tubulin clones with different restriction patterns have been isolated and characterized. At least seven of these clones contain the complete gene coding region. One clone appears to represent the transcribed alpha tubulin gene II. The sequence of an intron from this gene is compared with that from an equivalent gene in the rat. PMID- 2931166 TI - Characterization by nuclear magnetic resonance of the concanavalin A binding oligosaccharide on the beta b chain of placental beta-hexosaminidase B: lectin binding to the separated polypeptide chains of hexosaminidases A and B. AB - The type and distribution of the oligosaccharides on each polypeptide of human placental beta-hexosaminidases A (alpha (beta a beta b)) and B (2(beta a beta b)) were examined. The denatured polypeptides were separated by isoelectric focussing in a polyacrylamide slab gel and each gel was then overlaid with 125I-labelled lectins. The study indicated that the beta a chain contains negligible carbohydrate, the beta b chain contains both the high-mannose and a complex type oligosaccharide, and the alpha chain contains predominantly high-mannose or hybrid type moieties. Two asparagine-linked high-mannose type oligosaccharides present on the beta b polypeptide of beta-hexosaminidase B were isolated by concanavalin A chromatography and by reverse-phase high pressure liquid chromatography. Proton nuclear magnetic resonance characterization of the oligosaccharides revealed an equimolar glycan mixture of the high-mannose type structure Man5 and Man6. PMID- 2931167 TI - Role of diet fat in subcellular structure and function. AB - Current concepts of the biomembrane will be extrapolated to membranes of homeotherms to illustrate the influence of the nature of dietary lipid in nutritionally complete diets on membrane polar head group content and fatty acid composition. Utilizing animal models, the controlling influence of dietary long chain fatty acids on major lipid constituents of the mitochondrial membrane in cardiac tissue, the plasma membrane of liver, and the synaptosomal membrane in brain can be demonstrated. Diet-induced alterations in membrane composition are associated with demonstrable changes in the function of specific membrane proteins. To illustrate this relationship, the effect of diet on mitochondrial ATPase activity and on a hormone receptor-stimulated function in the plasma membrane of the liver will be discussed. These observations suggest that the diet fat modulates enzyme functions in vivo by changing the surrounding lipid environment in the membrane. PMID- 2931168 TI - Cardiac myofibrillar creatine kinase is not influenced by hypothyroidism. AB - The cardiac myofibrillar component of the phosphorylcreatine shuttle mechanism enzymatically couples the functionally significant processes of energy utilization (ATPase) with substrate regeneration by creatine kinase (CK). Both components have isoenzyme forms that are transcriptionally regulated. Propylthiouracil-induced (PTU) hypothyroidism reduced rat cardiac contractile protein ATPase activity by shifting isomyosin predominance from the V1 to the V3 form. However, neither CK specific activity or CK isoenzyme composition was altered by PTU treatment. Thus, myofibrillar components of the phosphorylcreatine shuttle, ATPase and CK, are not coordinately regulated under hypothyroid conditions. PMID- 2931169 TI - Release of atrial natriuretic peptide by atrial distension. AB - A heterologous radioimmunoassay was used to measure the concentration of immunoreactive atrial natriuretic peptide (iANP) in plasma from the femoral artery of eight chloralose anaesthetized dogs. Mitral obstruction which increased left atrial pressure by 11 cmH2O increased plasma iANP from 97 +/- 10.3 (mean +/- SE) to 135 +/- 14.3 pg/mL. Pulmonary vein distension increased heart rate but did not increase plasma iANP. Bilateral cervical vagotomy and administration of atenolol (2 mg/kg) did not prevent the increase in iANP with mitral obstruction. Samples of blood from the coronary sinus had plasma iANP significantly higher than simultaneous samples from the femoral artery confirming the cardiac origin of the iANP. Release of iANP depends on direct stretch of the atrium rather than on a reflex involving left atrial receptors. PMID- 2931170 TI - A reversible enteropathy complicating continuous hepatic artery infusion chemotherapy with 5-fluoro-2-deoxyuridine. AB - This article describes two patients with hepatic metastases from colorectal cancer in whom a reversible enteropathy developed during the administration of hepatic artery infusion chemotherapy with 5-fluoro-2-deoxyuridine (5-FUdR) via an Infusaid Series 400 pump (Infusaid Corp., Sharon, MA). Both patients had severe diarrhea and signs that suggested small bowel obstruction. Barium studies revealed a distinctive radiologic appearance of severe narrowing of the ileum associated with complete loss of normal mucosal patterns. Results of an extensive evaluation for an infectious or toxin-related enterocolitis were negative. Perfusion studies confirmed the appropriate position of the catheters and revealed no extrahepatic perfusion. Systemic shunting of the 5-FUdR through the liver or tumor bed is postulated as the primary event, with the small bowel manifesting the major toxicity. PMID- 2931171 TI - Complications of implantable chemotherapy pump. A case of pump inversion. AB - Regional chemotherapy with the use of implantable pumps is becoming more frequent. The authors report here a case of the pump inverting in the subcutaneous pocket. Speculation on diagnosis, correction, and prevention are discussed. PMID- 2931172 TI - The generation of interleukin-2-dependent suppressor T-cells from patients with systemic metastasis of gastric carcinoma and the phenotypic characterization of the cells defined by monoclonal antibodies. AB - Suppressor cells, which might be activated in patients with gastric carcinoma, were successfully enriched by the use of interleukin-2 (IL-2) prepared from human tonsils and spleens. That is, peripheral blood lymphocytes cultured for 3 or 4 weeks with IL-2 strongly inhibited the patient's own lymphocyte-proliferative responses to alloantigen or phytohemagglutinin (PHA). Quantitative fluorescence measurement for immunologic analysis of phenotypic characterization of the cells was made on FACS-IV with monoclonal antibodies anti-Leu-1 anti-Leu-2a, anti-Leu 3a, anti-Leu-4, anti Leu-5, anti-Leu-7, and anti-HLA-DR and goat anti-human immunoglobulin (Ig). Functional suppressor T-cells expanded with IL-2 showed the following phenotype: Leu-1+ Leu-2a+, Leu-3a-, Leu-4+, Leu-5+, Leu-7-, HLA-DR+, human Ig-. The IL-2-dependent suppressor T-cells could be obtained only when the cells were derived from patients with systemic metastasis of gastric carcinoma. These findings suggest that generation of IL-2-dependent suppressor T-cells is the result of large tumor burdens; this may exert negative cellular control in the immune responses, thus inducing the status of the lower cell-mediated antitumor immunity, and may promote cancer progression in gastric cancer patients. PMID- 2931173 TI - The so-called anticalmodulins fluphenazine, calmidazolium, and compound 48/80 inhibit the Ca2+- transport system of the endoplasmic reticulum. AB - We present evidence that a Ca2+- transport system of the endoplasmic reticulum with the "mitotic" Ca2+- ATPase as an essential component is another target for the anticalmodulin drugs fluphenazine, calmidazolium, and compound 48/80. Furthermore we show by affinity chromatography that there is a direct interaction between the solubilized Ca2+- ATPase and fluphenazine. Since the Ca2+- uptake system as well as the solubilized Ca2+- ATPase are calmodulin- free, the effect of fluphenazine, calmidazolium and compound 48/80 may be understood as a result of the interaction between these drugs and the Ca2+- ATPase. We propose that there are calmodulin- like sequences in the molecule of the Ca2+- ATPase. The inhibitory effect of these three drugs can be then explained by their recognition of the calmodulin- like structures. PMID- 2931174 TI - Solubilization of a high affinity CA-ATPase from dog antrum smooth muscle. AB - A Mg-independent high affinity Ca-ATPase has recently been reported to be present in the plasma membranes of smooth muscle. This enzyme has now been solubilized using deoxycholate. The membrane-bound and the solubilized enzymes resemble each other in Km for Ca2+, and inhibition by fluphenazine. The solubilized enzyme is, however, more sensitive to inhibition by Mg2+ than the membrane bound enzyme. Radiation inactivation analysis shows that whereas the membrane-bound enzyme had a target size of 98,000 +/- 4,000 Daltons, the solubilized enzyme was only 70,000, +/- 7,000 Daltons. PMID- 2931175 TI - Live and reactivated motility in the 9+0 flagellum of Anguilla sperm. AB - The sperm flagella of the eel, Anguilla anguilla, are capable of vigorous motion in spite of having an axoneme with reduced structure that lacks the outer dynein arms, radial spokes and spoke heads, the two central tubules and the central tubule projections that are all part of the standard "9+2" axoneme. These sperm progress forward rapidly as a result of the propagation of helicoidal waves distally along the flagellum. Their flagellar beat frequencies are high, 93 Hz at 21 degrees C, and they roll at a frequency of about 19 Hz. Eel sperm could be demembranated with Nonidet P-40 and reactivated with MgATP2- in 0.22 M K acetate at pH 8.1. The reactivated motility closely resembles that of the live sperm, with a beat frequency of 69 Hz, but the demembranated flagella are unusually fragile, and commonly disintegrate by a combination of splitting, coiling, and sliding within a few minutes. Little reactivation is obtained if acetate is replaced by Cl- in the reactivating medium. The Michaelis constant for beat frequency (0.2 mM) is similar to that obtained for several "9+2" flagella. These sperm, however, appear to lack the mechanism by which Ca2+ regulates waveform. Our results indicate that eel sperm flagella, which at rest are straight, are induced to bend helicoidally by ATP, as the result of sliding between tubules that is blocked at both the base and tip of the organelle. The flagellar waveform consists of a series of planar bends separated by short regions of right-handed twist, which give it an overall left-handed helicoidal form. PMID- 2931176 TI - Applicability of percutaneous transluminal coronary angioplasty to patients with recombinant tissue plasminogen activator mediated thrombolysis. AB - To test the utility and safety of percutaneous transluminal coronary angioplasty (PTCA) after recombinant tissue plasminogen activator (t-PA), we performed the procedure in all suitable candidates with acute myocardial infarction (MI) who had successful t-PA mediated coronary thrombolysis. Twenty consecutive patients with MI received t-PA after coronary angiographic conformation of total occlusion. Successful recanalization with t-PA was achieved in 13 patients, leaving a residual obstruction of 84 +/- 6% in the nine patients for whom PTCA was attempted at a mean of 21.6 h. Success was achieved in seven patients, leading to a residual lesion of 29 +/- 7%. In the two patients for whom PTCA was unsuccessful, total reocclusion occurred prior to the attempt despite therapy with heparin, aspirin, dipyridamole, and nifedipine. All PTCA procedures were uncomplicated. Serial two-dimensional echocardiography at 10 days, compared to admission, demonstrated infarct zone wall motion index improvement in the patients with successful PTCA (group A, 0.83 +/- 0.36 to 1.46 +/- 0.49) as compared to the 13 patients without thrombolysis or successful PTCA (group B, 0.61 +/- 0.26 to 0.66 +/- 0.39), (P less than 0.05). One patient of group A sustained a massive stroke at 2 weeks after hospital discharge. In the remaining six patients, follow-up exercise testing and/or coronary arteriography demonstrated a negative treadmill test and/or patent infarct vessel, respectively. After successful PTCA, no patient had clinical signs of reocclusion, reinfarction, postinfarction angina, or congestive heart failure. At 9.4 +/- 2 months, all six patients are asymptomatic and have returned to work. Thus, sequential PTCA after t-PA can be performed safely and successfully in patients with MI and this approach may be associated with improved regional function and a favorable post-MI course. PMID- 2931177 TI - Combined medical and mechanical recanalization in acute myocardial infarction. AB - A technique of combined medical and mechanical recanalization was employed in 96 patients with acute transmural myocardial infarction. The mean time between onset of symptoms and admission to hospital was 170 +/- 65 min (X +/- SD). After 10 +/- 16 min, 250,000 U streptokinase was administered intravenously for 20 min. Intracoronary thrombolysis was commenced within 38 +/- 14 min. First coronary angiograms demonstrated reperfusion, an open vessel in 25/96 patients (26%). In 15/71 patients (21%) reperfusion occurred during thrombolysis therapy, before mechanical recanalization could be performed. Recanalization was achieved mechanically in 37/71 patients (52%) with occluded coronary vessels. In 8/71 patients (11%) mechanical recanalization failed but the vessel opened during thrombolysis. In 12/96 patients (12%), the coronary vessel remained occluded. Thus, reperfusion could be achieved in 88% of the patients. Reperfusion rate was 76% in the first 38 patients and 95% subsequently. After reperfusion, coronary thrombi were found in 25/96 patients (26%) but dissolved during thrombolysis in 16/25 patients (64%). Peripheral coronary embolism was observed in 3/25 patients (12%). For the whole group, reocclusion occurred in 8/84 patients (10%). By combined medical and mechanical recanalization, the recanalization rate could be increased with low reocclusion rate. Trends showed an improvement in regional and global left ventricular function in patients with anterior myocardial infarction. PMID- 2931178 TI - Percutaneous balloon catheter angioplasty of coarctation of the abdominal aorta: report of two cases. AB - Two patients with coarctation of the abdominal aorta are reported. They both underwent successful transluminal balloon angioplasty. The immediate and short term results have been excellent. This method and its role in the treatment of coarctation of the abdominal aorta are discussed. PMID- 2931179 TI - Cardiac tamponade following percutaneous transluminal coronary angioplasty: four case reports. AB - Percutaneous transluminal coronary angioplasty (PTCA) has had complications related to dilating catheters and guide wires such as coronary artery dissection, spasm, rupture, and perforation. This report describes four patients who developed cardiac tamponade following PTCA, presumably from right ventricular (RV) perforation. All four received large doses of heparin during PTCA and three received antiplatelet therapy. In three cases, cardiac tamponade occurred several hours after PTCA. All patients did well following operative intervention and no patient required repair of a cardiac perforation. We postulate that impaired hemostasis in the presence of an otherwise inconsequential RV perforation causes tamponade. Three alternatives to provide standby pacing are proposed. PMID- 2931180 TI - Role of macrophages as modulators but not as autonomous accessory cells in primary antibody response. AB - The role of macrophages (M phi) in the in vitro primary antibody response of murine lymphocytes to sheep erythrocytes was investigated. Peritoneal M phi were activated to express Ia antigens either in vitro or in vivo. Nonactivated Ia- M phi were also examined. We observed that only Ia- M phi but also Ia+ M phi failed to trigger the antibody response, in contrast with splenic dendritic cells (DC) which served as potent and autonomous accessory cells, but that M phi modulated the level of response which was dependent primarily on the DC content of culture. The modulation appeared to incline to suppression rather than enhancement, when M phi were allowed to remain throughout the culture period for 4 days. A highly enhancing capacity of M phi, however, could be revealed by removing M phi 2 days after the initiation of culture, indicating that M phi exerted their suppressive effect more strongly in the late phase than in the early phase of in vitro antibody response. The modulatory activity seemed higher in Ia+ M phi than in Ia- M phi. PMID- 2931181 TI - Depression of afferent arc of the in vivo cytotoxic T-cell immunity by bacterial lipopolysaccharides. AB - The afferent arc of the in vivo cytotoxic T-cell immunity assessed by second set rejection of ascitic allogeneic tumors was shown to be depressed by bacterial lipopolysaccharide (LPS) that was administered simultaneously with or 1 day before injection of allogeneic spleen cells as stimulators. Two different LPSs from Escherichia coli O55 and Klebsiella O3 displayed similar activities whereas dextran sulfate, concanavalin A, or poly A:U was not effective. Stimulator activities of allogeneic cells was not directly modified by LPS. Any definite suppressor activity on afferent or efferent arc of the T-cell response was not demonstrable in mice receiving LPS and allogeneic cells. Further, the LPS effect for immune depression was not diminished by whole body X-ray irradiation to the recipient at 300 R, which ablated the B-cell reactivity to LPS for polyclonal activation, or by treatment of the recipient with carrageenan, a known toxic agent to macrophages. It was suggested from these results that LPS suppresses the cytotoxic T-cell immunity by modulating responder T cells to be temporarily refractory to the allogeneic stimulus rather than by activating suppressor cells such as radiation-sensitive lymphocytes and carrageenan-sensitive macrophages. PMID- 2931182 TI - Antigen-antibody complexes bound to B-lymphocyte Fc gamma receptors regulate B lymphocyte differentiation. AB - We studied the effect of soluble antigen-antibody complexes on the responses of polyclonally activated murine B lymphocytes. For this, normal B lymphocytes were stimulated with rabbit F(ab')2 anti-mu and lymphokines. IgG complexes, particularly in antigen excess, inhibited the plaque-forming cell response (55 70%), while proliferation was unaffected. Maximal inhibition was obtained with small amounts (0.2-1.0 microgram/ml) of complexes. Neither antigen or antibody alone was inhibitory. Inhibition was mediated via binding of the IgG complexes to Fc gamma receptors of B lymphocytes: (1) neither T lymphocytes or adherent accessory cells were required; (2) IgM complexes did not inhibit; and (3) inhibition was not seen when monoclonal anti-Fc gamma receptor antibodies prevented binding of the IgG complexes to these receptors. Kinetic experiments showed that B lymphocytes are susceptible to this inhibitory signal for only a short time after stimulation. We conclude that IgG complexes bound to the Fc gamma receptors of B lymphocytes regulate B-lymphocyte differentiation. PMID- 2931183 TI - Different functional subsets of cultured murine T cells express characteristic levels of adenosine deaminase activity. AB - The level of adenosine deaminase (ADA) activity in mouse T-lymphocyte cultures was studied under different growth-supporting conditions and in mixed lymphocyte culture-derived long-term T-cell lines and clones. Early after the initiation of in vitro culture, the levels of ADA (2000 U/mg) were similar in bulk cultures either depleted or not depleted in Lyt-2+ T cells. Enrichment for cytolytic T lymphocytes (CTL) obtained by addition of exogenous interleukin 2 (IL-2), was accompanied by a net decrease of ADA activity (110 +/- 15 U/mg). All the tested CTL-A lines derived from such cultures were also characterized by a low or undetectable level of this enzyme (at best 160 +/- 70 U/mg) as previously observed. In contrast, "Lyt-2-" T-cell bulk cultures grown, without addition of exogenous IL-2, in the presence of gamma-irradiated H-2d stimulators maintained a constant level of ADA activity (1770 +/- 340 U/mg) for at least 3 months. Functionally distinct types of Lyt-2- T-cell lines were also analyzed: T-cell lines competent to activate B lymphocytes to growth and terminal maturation as well as others devoid of detectable functions showed a stable ADA level comparable to that expressed by the original bulk culture 1685 +/- 620 U/mg). The present results demonstrate that, like tumor cell lines, most normal T lymphocytes express a high level of ADA activity in culture, which strongly suggests that the low level of ADA activity exhibited by CTL is a characteristic of this functional subset. PMID- 2931184 TI - beta-Carotene reduces sister chromatid exchanges induced by chemical carcinogens in mouse mammary cells in organ culture. AB - Present studies in the mammary epithelial cell transformation model in organ culture showed that presence of beta-carotene during the 24 hr treatment (initiation stage) of the glands with the carcinogens, 7,12 dimethylbenz[a]anthracene (DMBA), N-nitrosodiethylamine (DENA) and N methylnitrosourea (MNU), caused a highly significant (P less than 0.001-0.01) reduction of SCE induced by the same carcinogens. In contrast, 4-hydroxyphenyl retinamide (4-HPR) which is known to act at the promotional stage of carcinogenesis did not show any significant reduction of SCE. Thus findings suggest that beta-carotene can modify the DNA damaging effect of the carcinogens and thereby may also prevent the initiation of the carcinogenic process. PMID- 2931185 TI - Actions of exogenous heparan sulfate and hyaluronic acid on growth and thymidine incorporation of normal and transformed human fibroblasts. A comparison with the effects of high cell density and low serum concentration and a warning against thymidine incorporation as a measure of DNA synthesis. AB - Treatment of normal human (WI-38) cells with exogenous heparan sulfate (HS) reduced cell growth and incorporation of radio-isotope-labeled thymidine (TdR) into DNA. In spite that growth of their transformants (WI-38 CT-1) was enhanced by HS treatment, transformed cells also decreased in TdR incorporation thereby. This peculiar observation was explained by a reduction of TdR uptake, leading to a decrease in specific radioactivity of newly synthesized DNA. The changes in cell growth and TdR incorporation by HS treatment were revealed to be similar to the changes with increasing cell density rather than by serum starvation. PMID- 2931186 TI - Widespread absence of outer dynein arms in the spermatozoids of lower plants. AB - Transverse sections of flagellar axonemes from a variety of lower plant spermatozoids were examined by electron microscopy. Motile sperm of four ferns (Marsilea, Pteridium, Lygodium and Aneimia), a horsetail (Equisetum) and a liverwort (Marchantia) were fixed in the presence of tannic acid to visualise the dynein arms. In all cases the inner dynein arms were clearly resolved but the outer arms were absent. Absence of outer arms therefore appears to be a common feature of the archegoniate plants. The implications of these findings to our understanding of the evolution of the land plants and the role of the dynein arms in flagellar beating is discussed. PMID- 2931187 TI - Association of anti-dynein-1 cross-reactive antigen with the mitotic spindle of mammalian cells. AB - Two anti-dynein-1 antibodies were affinity-purified from rabbit antiserum produced by immunization with dynein-1 from sea urchin sperms. One was prepared with dynein-1 as the ligand and the other with the A heavy chains of dynein-1 as the ligand. In Western blots of axonemal proteins, the former antibody reacted with the A heavy chains of dynein-1 as well as with several other smaller polypeptides, whereas the latter bound almost exclusively to the A heavy chains. PtK2 cells stained by indirect immunofluorescence with either of these antidyneins had identical fluorescence patterns. The interphase cell showed rather diffuse and weak fluorescence in its nucleus and perinuclear cytoplasm. Its primary cilium and its centrioles also fluoresced. During prophase and prometaphase, a more intense fluorescence was present in the asters and developing spindle. During metaphase and anaphase the half-spindles fluoresced intensely in a fibrous pattern that corresponded to that of the spindle fibers, showing less intense fluorescence in the anaphase interzone. In telophase and early interphase, the intercellular bridge on each side of the midbody also was stained. These results are evidence that dynein-1, specifically the A heavy chains and/or a related antigen, is densely packed in the mitotic spindle of PtK2 cells. PMID- 2931188 TI - [Laparoscopic diagnosis of pelvic endometriosis in sterile women]. PMID- 2931189 TI - [The significance of uroflowmetry in evaluating urination disorders in women]. PMID- 2931190 TI - Interaction of protein-bound polysaccharide (PS-K) with microtubule proteins. V. Influence on tubulin-dependent adenosine triphosphatase (ATPase) activity. PMID- 2931191 TI - Specificity of esterases and structure of prodrug esters. II. Hydrolytic regeneration behavior of 5-fluoro-2'-deoxyuridine (FUdR) from 3',5'-diesters of FUdR with rat tissue homogenates and plasma in relation to their antitumor activity. PMID- 2931192 TI - [Utilization and culture Of Fritillaria thunbergii]. PMID- 2931193 TI - [Historical textual research on medicinal plants of Dioscoreaceae in Zhejiang Province]. PMID- 2931194 TI - [Identification of adulterants of Bungarus multicinctus]. PMID- 2931195 TI - [Effect of Chinese materia medica after the processing with wine]. PMID- 2931196 TI - [Formulation of a wax shell for honey pills: II. Orthogonal experiment of the eight factors of the formulation of the wax shell]. PMID- 2931197 TI - [Improved preparation of hepatitis syrup]. PMID- 2931198 TI - [Chemical constituents of Equisetaceae: a review]. PMID- 2931199 TI - [Isolation and identification of chemical constituents from an alcoholic extract of Notopterygium incisium]. PMID- 2931200 TI - [Preliminary study of Cordyceps barnesii--comparison of the chemical constituents of Cordyceps barnesii and Cordyceps sinensis]. PMID- 2931201 TI - [Anti-inflammatory effect of the volatile oil from Curcuma aromatica]. PMID- 2931202 TI - [Mitotic effect of radix codonopsis pilosulae, radix astragali and semen strychni on human lymphocytes]. PMID- 2931203 TI - [Effect of the compound of Choerospondias axillaris on the tolerance to hypoxia and protection from acute myocardial ischemia in animals]. PMID- 2931204 TI - Preparation of functional group analogs of unsaturated fatty acids and their effects on the circadian rhythm of a fatty-acid-deficient mutant of Neurospora crassa. AB - Functional group analogs of oleic, linoleic and linolenic acids were prepared by coverting their double bonds to dibromo, cyclopropyl, epoxy, methoxy, and, in the case of oleic acid, hydroxy groups. These compounds were supplemented to the bd csp cel strain of the mold Neurospora crassa. The cel mutation confers a partial requirement for saturated fatty acids and, also, perturbs the circadian rhythm of spore formation. For example, the period of bd csp cel's rhythm is dramatically lengthened upon supplementation by natural cis-unsaturated fatty acids. Of the analogs tested, only the monoepoxy, monomethoxy, dibromo, and hexabromo stearic acids gave significant period lengthening. Other analogs, which should have comparable abilities to disrupt lipid bilayer packing, gave no rhythm effect. Further, the inactive di- and tri-methoxystearic acid analogs were incorporated to a greater extent than the active mono-methoxystearic acid. The results do not, therefore, support a direct alteration in membrane "fluidity' as the mode of action of the period-lengthening fatty acids. PMID- 2931205 TI - Invasive cervical cancer and depot-medroxyprogesterone acetate. WHO Collaborative Study of Neoplasia and Steroid Contraceptives. AB - Preliminary results of a study of the possible relationship of depot-medroxy progesterone acetate (DMPA) to invasive cervical cancer are presented. The findings are based on data from three participating centres in Thailand and one in Mexico. A relative risk for cervical cancer of 1.2 was observed in women who had ever used DMPA; this was not statistically significant. No consistent increase in risk with duration of use was observed, although a relative risk of 2 was found in women who had used DMPA for more than 5 years. This observed increase in risk was confined to women who were aged under 46 years or who had first been exposed to DMPA before 30 years of age. These findings are based on small numbers of subjects, and may not represent a causal relationship. PMID- 2931206 TI - Breast cancer and depot-medroxyprogesterone acetate. WHO Collaborative Study of Neoplasia and Steroid Contraceptives. AB - The preliminary results of a study of the incidence of breast cancer in relation to use of depot-medroxyprogesterone acetate (DMPA) are presented. The findings are based on data from three participating centres in Thailand, and one each in Kenya and Mexico. A relative risk for breast cancer of 0.7 was observed in women who had ever used DMPA; this was not statistically significant. Although no consistent decrease in risk with duration of use was observed, the lowest relative risk (0.5) was observed in women who had used DMPA for three or more years. These findings are based on small numbers and must be considered preliminary. However, they provide no evidence that DMPA increases the risk of breast cancer, and suggest that it may exert a protective effect, particularly in long-term users. PMID- 2931207 TI - The unchanging epidemiology and toll of measles in Burma. PMID- 2931208 TI - By-pass of the major aminofluorene-DNA adduct during in vivo replication of single- and double-stranded phi X174 DNA treated with N-hydroxy-2-aminofluorene. AB - To examine the effects of aminofluorene-DNA adduct formation on the biological activity of DNA, single-stranded (ss) phi X174 DNA and phi X174 replicative form (RF) DNA were modified to different extents with 3H-labeled N-hydroxy-2 aminofluorene and subsequently transfected to Escherichia coli spheroplasts with different repair capabilities. When the fraction of active ss phi X174 DNA molecules was measured as a function of the mean number of adducts per molecule, exponential survival curves were obtained from which it could be deduced that in wild-type, uvrA- and recA- cells at least 86%, and in uvrC- cells at least 82% of the introduced adducts do not cause inactivation. In the case of RF DNA the survival curves are non-exponential, but they nevertheless show that an exceptionally high number of adducts per RF molecule must be introduced to destroy its biological activity. On average 52 adducts per RF molecule were needed to reduce the survival to 37%, irrespective of whether wild-type, uvrA- or recA- cells were used. On the other hand, the survival of the uvrC- cells was considerably lower, but even in these cells a majority of the adducts is not lethal. By h.p.l.c. analysis of the modified DNA after hydrolysis with trifluoroacetic acid, 81 and 84% of the adducts in ss- and RF DNA, respectively, could be identified as N-(guanin-8-yl)-2-aminofluorene. The results strongly indicate that this type of major modification product is very frequently by passed during replication of both single- and double-stranded DNA. The results together with the data obtained by sucrose gradient analysis both before and after an alkali treatment and those obtained by h.p.l.c. analysis suggest that inactivation of ssDNA is mainly due to minor modifications such as secondary lesions consisting of chain breaks and alkali-labile sites together with unidentified interaction products. PMID- 2931209 TI - Role of sodium in hypertensive cardiac hypertrophy. AB - Cardiac hypertrophy in systemic hypertension may not result simply from increased afterload. Previous studies indicate that factors other than blood pressure may influence cardiac hypertrophy. We evaluated the effects of dietary sodium restriction in two-kidney one-clip renal hypertensive rats. After the renal artery had been clipped, the rats received a normal diet until hypertension was established; thereafter, a sodium-deficient diet was instituted in one group. Clipped rats on a regular diet had significantly higher systolic blood pressures than sham-operated controls (205 +/- 9 vs. 129 +/- 1 mm Hg, respectively). Sodium restriction did not reverse hypertension (190 +/- 8 mm Hg), but led to a significant reduction of relative heart weight compared to rats on the normal diet (2.94 +/- 0.24 vs. 3.86 +/- 0.23 mg/g, respectively; P less than 0.01). The hypertrophied hearts of animals on the regular diet showed depressed tissue catecholamines (significant only for norepinephrine); sodium restriction resulted in a restoration to normal levels. Thus, we demonstrated a dissociation of blood pressure and cardiac hypertrophy in the two-kidney one-clip model, similar to previous findings in other models. Our results support the concept that factors other than blood pressure contribute to cardiac hypertrophy. Dietary sodium intake appears to be one such factor. In addition, a possible role of the sympathetic nervous system is suggested. PMID- 2931210 TI - The effects of human atrial 28-amino acid peptide on systemic and renal hemodynamics in anesthetized rats. AB - The effects of synthetic human atrial 28-amino acid peptide (alpha-human atrial polypeptide) on systemic and renal hemodynamics were examined in two separate groups of Inactin-anesthetized rats. First, mean arterial pressure, heart rate, and cardiac output were measured before and during infusion of the peptide at rates of 0.04-0.67 microgram/kg per min. Cardiac output was determined by the dye dilution method with a microcuvette inserted into a carotid-femoral arterial shunt. After 10 minutes of infusion, mean arterial pressure, cardiac output, and total peripheral resistance were reduced in a dose-dependent manner by 21% (P less than 0.001), 9% (P less than 0.05), and 11% (P less than 0.05), respectively, with 0.67 microgram/kg per min of alpha-human atrial natriuretic polypeptide. Despite the marked fall in blood pressure, the heart rate did not change. Second, urine volume, urinary sodium excretion, glomerular filtration rate ([3H]inulin clearance) and renal blood flow ([14C]p-aminohippuric acid sodium clearance and hematocrit) were measured. Increases in urine volume, urinary sodium excretion, filtration fraction, and fractional sodium excretion and a decrease in renal vascular resistance were dose dependent: +490% (P less than 0.01), +1340% (P less than 0.01), +19% (P less than 0.05), +1160% (P less than 0.01), and -18% (P less than 0.05), respectively, with 0.67 microgram/kg per min of alpha-human atrial natriuretic polypeptide. The glomerular filtration rate increased with 0.33 and 0.67 microgram/kg per min of alpha-human atrial natriuretic polypeptide (both P less than 0.05), whereas renal blood flow did not change.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2931211 TI - In-hospital morbidity and mortality in patients undergoing elective coronary angioplasty. AB - We prospectively recorded all in-hospital complications of the first 3500 consecutive patients to undergo elective coronary angioplasty (PTCA) at Emory University Hospitals from July 14, 1980, to August 28, 1984, by three operators. PTCA was attempted in a total of 3933 lesions, with a primary success rate of 91%. Multiple-lesion PTCA was performed in 401 patients, and PTCA of saphenous vein grafts was attempted in 172. No complications were recorded in 3116 (89%) cases, isolated minor complications occurred in 241 (6.9%), and major complications (emergency surgery, myocardial infarction, death) were observed in 145 (4.1%). Emergency coronary artery bypass graft surgery (CABG) was performed in 96 patients (2.7%), with a myocardial infarction rate of 49% (47/96), a Q wave infarction rate of 23% (22/96), and an emergency surgery mortality rate of 2% (2/96). Hospital discharge occurred within 2 weeks of attempted PTCA in 91% (87/96) of patients undergoing emergency CABG. The overall myocardial infarction rate was 2.6% (94/3500). There were two nonsurgical deaths, giving a total mortality rate of 0.1% (4/3500). Univariate and multivariate analysis of 3099 patients undergoing single-lesion PTCA identified five preprocedure predictors of a major complication: multivessel coronary disease, lesion eccentricity, presence of calcium in the lesion, female gender, and lesion length. Unstable angina, duration of angina, lesion severity, previous CABG, and vein graft dilatation were not associated with an increased incidence of major complications. The strongest predictor of a major complication was the procedural appearance of an intimal dissection. Intimal dissection was evident in 894/3099 (29%) patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2931212 TI - Uptake of hematoporphyrin derivative by valvular vegetations in experimental infective endocarditis. AB - Drugs that localize in valvular vegetations may be useful in the diagnosis and treatment of infective endocarditis. We therefore tested the hypothesis that parenterally injected hematoporphyrin derivative (HPD), which is concentrated in tumors and atherosclerotic plaques, localizes in the vegetations of experimental infective endocarditis. In 14 rabbits, various bacteria were given intra arterially immediately after injury to the aortic valve. In 12 additional rabbits, sterile vegetations on the aortic valve were produced by the trauma caused by an indwelling catheter that had been in place over a long period. HPD, 2.5 mg/kg, was injected intravenously 1 to 2 days before the animals were killed in six rabbits with sterile vegetations and in seven rabbits with infected vegetations. In all rabbits, multiple vegetations on the aortic valve leaflets were identified. On exposure to ultraviolet light, strong porphyrin fluorescence of all vegetations, whether sterile or infected, was observed only in rabbits given HPD. In two rabbits given HPD 10 weeks after catheter implantation across the aortic valve, however, only mild fluorescence could be detected in healing endocardial vegetations. In frozen sections of HPD-laden lesions, a patchy distribution of fluorescence was observed that was similar to the pattern of HPD localization in atheromatous plaques. Since vegetations in experimental infective endocarditis selectively concentrate HPD, porphyrins could be useful in the diagnosis and treatment of infective endocarditis. PMID- 2931213 TI - Solid-phase enzyme-receptor assay (SPERA): a competitive-binding assay for glycopeptide antibiotics of the vancomycin class. AB - A solid-phase enzyme-receptor assay (SPERA) has been developed for glycopeptide antibiotics of the vancomycin class such as teicoplanin, vancomycin, ristocetin, avoparcin, actaplanin, A-47934, A-41030, and A-35512-B. The assay exploits the mechanism of most action of these antibiotics, which is based on their interaction with acyl-D-alanyl-D-alanine, a constituent of the walls of most growing bacterial cells. The antibiotics and enzyme-labeled teicoplanin compete for a synthetic analog of the biological receptor, albumin-epsilon-aminocaproyl-D alanyl-D-alanine. The various antibiotics produced different competition curves, 50% displacement being obtained with antibiotic concentrations ranging from 0.04 to 4 mg/L, vancomycin and actaplanin being the weakest and strongest competitors, respectively. For teicoplanin in human serum the intra-assay CV was 7.2%, the interassay CV was 11.2%, and the analytical recovery 94%. Teicoplanin concentrations obtained by SPERA (chi) correlated well with those obtained by microbiological assay (y): y = 1.03 chi + 0.053 (r = 0.943; n = 60). We conclude that SPERA is a powerful tool for identification and quantitative detection of glycopeptide antibiotics, even in complex media. PMID- 2931214 TI - The analysis of systolic and diastolic time intervals: a more sensitive non invasive method in the assessment of left ventricular dysfunction in the patients with essential hypertension. AB - Time indices and volumetric parameters were investigated in patients with essential hypertension subdivided into three groups according to the WHO stage classification. The ratio of ejection time (ET) and pre-ejection period (PEP), ET/PEP remained within normal range in WHO-I but decreased significantly in WHO II and reached extremely low values in WHO-III. ET did not change in WHO-I and WHO-II but became significantly reduced in WHO-III. Prolongation of PEP in WHO-II and WHO-III increased with progression of hypertensive stage. Isovolumic relaxation time (IRT) showed the same pattern as the prolongation of PEP; positive correlation between PEP and IRT was observed (r=0.55). On the other hand, significant changes of volumetric parameters were only observed in WHO-III. These results indicated that the time indices were a more sensitive parameter than the volumetric ones in the assessment of left ventricular dysfunction in the patients with essential hypertension. PMID- 2931215 TI - Enhanced natriuretic and hypotensive responsiveness to alpha-human atrial natriuretic polypeptide (alpha-hANP) in SHR. AB - Natriuretic and hypotensive effects of synthetic alpha-human atrial natriuretic polypeptide (alpha-hANP) were investigated in anesthetized spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). The renal excretory and hypotensive effects of alpha-hANP were strengthened in a dose dependent manner in both strains of rat. The natriuretic response to three doses of alpha-hANP (0.3, 1.0 and 3.0 micrograms/kg) were significantly greater in SHR than in WKY. These results suggest that atrial natriuretic polypeptide may play some role in water-electrolyte balance and control of blood pressure in SHR. PMID- 2931216 TI - Age of onset in siblings of persons with juvenile Huntington disease. AB - The age of onset distribution of Huntington disease (HD) has been defined for siblings of patients who exhibit the disease before age 20. The mean age of onset for the siblings of juvenile onset cases is 26.8 years, which is significantly less than the mean age of onset (39.8) observed in siblings of non-juvenile cases. We have shown that the curve for age of onset in the general affected population is significantly different from that of the juvenile sibships. Furthermore, the significant regression equation suggests that the 'expected age of onset' of a sibling can be predicted from a knowledge of the age of onset of the juvenile proband. This information can be used to predict a range of age of onset for those sibs of juvenile patients who are likely to be asymptomatic heterozygotes with DNA polymorphism studies. PMID- 2931217 TI - The effects of isotretinoin on the pathology of early acne papules. PMID- 2931218 TI - Reticulate pigmented anomaly of the flexures and seborrhoeic warts. PMID- 2931219 TI - Lymphocytes from patients with hairy cell leukaemia enable the distinction of two separate subpopulations of activated lymphocyte killer cells generated in mixed lymphocyte culture. AB - Blood from patients with hairy cell leukaemia (HCL) was used to investigate subpopulations of the non-specific activated lymphocyte killer (ALK) cells generated in mixed lymphocyte culture (MLC). Mononuclear cells from four of five patients with HCL had decreased natural killer (NK) cell activity and, of these, all showed a decrease in ALK cell activity against K-562 target cells (NK like cells), but three had normal levels of ALK cells able to kill melanoma cells. One patient who had received splenectomy had normal NK cell activity, and in MLC his cells generated normal levels of both subpopulations of ALK cells. The results support the hypothesis of separate subsets of ALK cells: NK like cells with NK cell precursors and which preferentially lyse the K-562 target cell and a second separate population which arises independent of NK cell precursors and which has strong cytolytic activity against an NK insensitive melanoma cell line. PMID- 2931221 TI - T suppressor cell function and number in children with liver disease. AB - Con A stimulated suppressor cell function and the proportion of suppressor T cells were reduced in children with untreated chronic active hepatitis (CAH) but were normal in corticosteroid treated CAH patients, patients with severe acute hepatitis and inactive chronic liver disease. Adults with CAH also have defective suppressor function but a normal proportion of T suppressor cells. This difference may account for the observation that relapse after treatment withdrawal is less frequent in children than in adults. PMID- 2931220 TI - Strong prostaglandin associated suppression of the proliferation of human maternal lymphocytes by neonatal lymphocytes linked to T versus T cell interactions and differential PGE2 sensitivity. AB - Lymphocytes from human fetuses and newborns strongly, regularly, and non specifically suppress the proliferation of PHA stimulated peripheral blood mononuclear leucocytes. The suppression is prostaglandin (PG)-dependent. Our present investigation clearly indicates that the suppression is associated with neonatal T versus maternal T lymphocyte interactions, independent of monocytes. This was borne out from co-cultures of PHA stimulated maternal and male cord T cells enriched by nylon wool columns (greater than 90% T3+ cells; residual adherent cells ranging between 0 and 0.05%, and sIg+ cells between 0.6 and 3.2%). Sex chromosomes served as markers for dividing cord (male) or maternal cells. Each of three separate PG synthetase inhibitors introduced into the co-cultures indomethacin 28 microM, 5, 8, 11, 14-eicosatetraynoic acid (ETYA) 33 microM, or Naprosyn 217 microM--decreased the suppression of the maternal T cells by a maximum of 65%, indicating the importance of PG for the suppression. Moreover, exogenous PGE2 ranging between 1.4 X 10(-5) and 1.4 X 10(-9) M strongly suppressed the proliferation of PHA stimulated maternal T cells (ranging between 62 and 26%) but left the proliferation of cord T cells virtually unchanged. This difference offers one explanation for the strong and invariable suppression of adult lymphocytes by fetal/neonatal lymphocytes. The suppression might be of importance for prohibiting rejection of the placenta by maternal lymphocytes. PMID- 2931222 TI - In vitro studies on the mechanism of increased serum IgM levels in primary biliary cirrhosis. AB - To evaluate the mechanisms underlying the increase in serum IgM in primary biliary cirrhosis (PBC) studies were designed to examine IgM production in vitro and to assess the relative contribution of intrinsic B cell activity and immunoregulatory T cell balance to IgM synthesis. The number of peripheral blood lymphocytes (PBL) producing IgM (spontaneous and pokeweed mitogen (PWM) stimulated) at the end of a seven day culture period was similar in PBC patients and control subjects while the amount of IgM synthesized (spontaneous and PWM stimulated) during this period was significantly greater in the patient group, implying that the amount of IgM produced per B cell was increased in PBC. Co culture of autologous and allogeneic T and B lymphocytes and irradiation of T lymphocytes from patients and normal subjects clearly implicated abnormal suppressor T cell function, rather than autonomous B cell hyperactivity, as the cause of the increased IgM synthesis. Direct studies of T cell function indicated that although concanavalin A (Con A) activated suppressor cells inhibited proliferation of IgM producing B cells in the majority of PBC patients, they were unable to inhibit IgM synthesis. The demonstration of a disparity between IgM synthesis and the proliferation of IgM-producing B cells, together with the observation that the abnormality of T cell function is largely confined to the control of IgM secretion, is consistent with the presence of at least two different suppressor subpopulations regulating IgM production. In PBC the main suppressor cell abnormality seems to affect regulation of IgM secretion rather than B cell proliferation. PMID- 2931223 TI - Effect of in vitro colchicine and oral theophylline on suppressor cell function of asthmatic patients. AB - Extrinsic asthmatic patients have been reported to have a deficiency of concanavalin A (Con A)-induced suppressor cell function. We tested whether in vitro colchicine and oral theophylline can correct this immunoregulatory abnormality. Asthmatic patients' mononuclear cells were incubated with Con A and/or colchicine and then suppression of proliferation was measured by coculture of these cells with healthy volunteers' mononuclear cells and phytohaemagglutinin. The Con A induced suppressor cell function of 29 theophylline treated patients (26 +/- 16%, mean +/- s.d.) was significantly (P less than 0.002) increased as compared to 21 untreated patients (12 +/- 10%) but significantly (P less than 0.01) decreased as compared to 45 healthy volunteers (39 +/- 17%). A pharmacological concentration (10(-8) M) of colchicine had no significant effect on Con A-induced suppressor cell function of 19 untreated patients (from 12 +/- 9% to 9 +/- 22%) but significantly (P less than 0.05) increased Con A-induced suppressor cell function of 20 theophylline treated patients (from 26 +/- 17% to 36 +/- 19%). Thus asthmatic patients have decreased Con A-induced suppressor cell function which is partially corrected by oral theophylline and almost completely corrected by oral theophylline plus in vitro colchicine. This synergistic effect raises the possibility that oral colchicine together with theophylline may be useful in treating patients with extrinsic asthma. PMID- 2931224 TI - Salivary IgA antibody to glucosyltransferase in man. AB - Parotid salivas of 97 young adults were screened for IgA antibody to glucosyltransferase (GTF) from laboratory strains of Streptococcus mutans (serotypes c and g). Antibody levels to GTF from serotype c positively correlated with levels to serotype g GTF among these salivas. GTF's were prepared from S. mutans obtained from a subset of individuals in this population. All but one saliva showed IgA antibody activity to all of the GTF tested. In addition, the relative magnitude of each subject's antibody level was generally the highest to the GTF from their own S. mutans. Fractions, enriched for IgA by ammonium sulphate precipitation and gel filtration, showed patterns of functional inhibition of GTF activity which were consistent with patterns of IgA antibody activity in ELISA of unfractionated salivas. These data indicate that detectable levels of IgA antibody to S. mutans GTF exist in many young adult salivas, while this IgA antibody activity reacts with GTF from different biotypes, subjects generally show the highest secretory IgA antibody levels to their own GTF, and the relative amount of IgA antibody to GTF and the ability to inhibit GTF activity are roughly correlated. PMID- 2931225 TI - T gamma lymphocytosis is clinically non-progressive but immunologically heterogeneous. AB - Immunological studies were performed with the expanded T gamma cells of five patients with T gamma lymphocytosis. All patients showed a stable clinical picture with persistent T gamma lymphocytosis and neutropenia, with or without recurrent infections. The expanded T gamma cells in the blood had the T1-3+4 8+11+M1- phenotype, with the exception of one patient whose cells lacked the T8 marker. The expanded T gamma cell population did not proliferate in response to T cell mitogens and did not show immunoregulatory activity on pokeweed mitogen driven immunoglobulin synthesis. In four of the five patients the T gamma cells had killer cell activity against IgG sensitized mouse mastocytoma cells. Taken together, these results and the data from the literature, it is concluded that T gamma lymphocytosis represents a spectrum of T cell expansions clearly distinct from clinically progressive mature T cell neoplasias. PMID- 2931226 TI - Specific cytotoxicity of human lymphocyte subpopulations defined by bacterial adherence. AB - It has been shown that lymphocytes can be subdivided into subpopulations based on their binding of bacteria. Monolayers of immobilized and fixed bacteria were used here to separate T cells into BA-T1T2, adherent to Escherichia coli-2 (EC-2+) and BA-T3T4, non-adherent to this strain of bacteria (Ec-2-) (our denomination). The cells were activated in mixed lymphocyte cultures (MLC) and tested for cytotoxic activity. The BA-T1T2 cells developed the same cytotoxic activity as the sham separated T cells whereas BA-T3T4 cells did not become cytotoxic. When the T cells were separated into BA-T2 cells, adherent to Bacillus globigii (Bg+), and BA-T1T3T4, non-adherent, (Bg- cells became cytotoxic. Since BA-T1 cells, which represent 10-20% of T cells, are common to the two populations they appear to contain all T cells needed to develop the specific cytotoxicity for allogeneic cells. When the cells were first activated in MLC for 6 days and then separated by adherence to E. coli-2 or B. globigii, all cytotoxic cells were in the non adherent fraction. We concluded that the subpopulation of T cells which are Ec 2+Bg- (less than 20%) contain all the cells required for the development of cytoxic cell function and that after activation they become Ec-2-Bg-. PMID- 2931227 TI - Numerical and functional alterations in circulatory lymphocytes in cigarette smokers. AB - Simultaneous numerical and functional studies of circulatory lymphocytes were undertaken in healthy non-smoking and cigarette-smoking volunteers. The smokers all had light to moderate histories of less than 50 pack years. By contrast with non-smokers (n = 32), the smokers (n = 14) had a significant increase in the total number of lymphocytes, surface immunoglobulin bearing (sIg+) cells, total T cells (T3+) and T helper-inducer cells (T4+), and a trend of increase in T suppressor-cytotoxic cells (8+). These changes differ from those in heavy smokers who have been reported to show significantly increased T suppressor-cytotoxic but significantly decreased T helper-inducer cells. Although the proportions of T cell subsets did not differ significantly in the light to moderate smokers compared with non-smokers, in vitro T-suppressor function against the Ig secreting response of allogeneic B-cells to pokeweed mitogen (PWM) stimulation was significantly impaired. The proliferative response of T-cells to phytohaemagglutinin (PHA) was, however, similar in both groups. This suggests that smoking may exert a selective influence upon a subset of T suppressor cells. In cytotoxicity assays, smokers showed a significant decrease in natural killer cell (NK) activity but not in antibody dependent cellular cytotoxicity (ADCC). It appears that these alterations are reversible since a group of ex-smokers (n = 10) were indistinguishable from our non-smoking group in all studies. The implications regarding the link between smoking and increased susceptibility to infection and malignancy are discussed; and these findings should be borne in mind in basic studies of lymphocytes. PMID- 2931229 TI - Ultrasonic blood flow measurements in arteriovenous fistulas: an experimental study. AB - Femoral arteriovenous fistulas (AVF) were constructed in dogs. Fistulas blood flow was measured simultaneously with standard Doppler equipment, with electromagnetic flow probes and by direct timed blood collection. A good correlation was observed between Doppler and direct timed blood collection (r = 0.822, p less than 0.001) and also between Doppler and electromagnetic determinations (r = 0.747, p less than 0.001). These results lead us to suggest that transcutaneous measurement of AVF flow is possible with standard Doppler equipment and we recommend this technique for the management of AVF constructed in uremic patients. PMID- 2931230 TI - Management of patients after thrombolytic therapy for acute myocardial infarction. AB - The coronary artery thrombus that causes acute myocardial infarction can be lysed, and reperfusion can be achieved, in the first few hours after infarction. However, the infarct vessel will reocclude in 15-30% of patients, and this event is frequently associated with pain, reinfarction, arrhythmias, or death. The risk of reocclusion is greatest in patients with high-grade residual stenosis after thrombolysis. Percutaneous coronary angioplasty may be performed safely after thrombolytic therapy. Angioplasty effectively decreases the degree of residual stenosis, and may thereby reduce the risk of reocclusion and consequent ischemic events. However, a substantial proportion of patients with acute infarction are not suitable candidates for angioplasty. Coronary artery bypass surgery has also been safely performed within several days after thrombolytic therapy. Further studies are needed to determine which patients will benefit most from this aggressive approach to acute myocardial infarction. PMID- 2931228 TI - The oestrogen antagonists, tamoxifen and FC-1157a, display oestrogen like effects on human lymphocyte functions in vitro. AB - We studied the in vitro effects of two anti-oestrogens (tamoxifen and FC-1157a) on human lymphocyte functions in pokeweed mitogen (PWM) stimulated cultures. Addition of 1-100 nmol/l of tamoxifen or FC-1157a to PWM cultures significantly increased the number of immunoglobulin secreting cells. This concentration of tamoxifen did not affect the proliferative response. Further experiments with fractionated lymphocyte subpopulations showed that the anti-oestrogens displayed their enhancing effect by inhibiting the suppressive function of T8+ cells. The anti-oestrogens had no significant effect on the T-independent activation of B cells with Epstein-Barr virus. We conclude that the anti-oestrogens display an effect on the functions of human lymphocytes similar to that previously reported for oestradiol (Paavonen, Andersson & Adlercreutz, 1981). PMID- 2931231 TI - Right ventricular subendocardial infarction in a patient with pulmonary hypertension, right ventricular hypertrophy, and normal coronary arteries. AB - Right ventricular infarction is usually associated with coronary artery disease and concomitant left ventricular infarction. Isolated right ventricular subendocardial necrosis was discovered at autopsy in a 52-year-old woman with pulmonary hypertension, right ventricular hypertrophy, and normal coronary arteries, who died with septicemia 41 days after mitral valve replacement. This represents the first well-documented report of isolated right ventricular subendocardial infarction associated with normal coronary arteries. PMID- 2931232 TI - Antihypertensive and cardiovascular effects of nitrendipine: a controlled study vs. placebo. AB - The antihypertensive and cardiovascular effects of nitrendipine, a calcium entry blocker similar to nifedipine, have been evaluated in a double-blind, placebo controlled study in 20 patients with hypertension. At baseline and at the end of the 8-week period (nitrendipine, 20 mg once a day, or placebo, 1 tablet once a day) the following parameters were measured: systolic and diastolic blood pressure (BP) and heart rate (HR) at rest by an automatic recorder; BP, HR, and cardiac workload (systolic BP X HR) during exercise testing on a bicycle; left ventricular mass (LVMe according to the method of Devereux) and cross-sectional area (CSA), and main parameters of systolic function (end diastolic volume, end systolic volume [ESV], and ejection fraction [EF]) by M mode echocardiography. There was a significant decrease in BP at rest (163/108 vs. 144/92 mm Hg; P less than 0.001) and during exercise in subjects receiving nitrendipine, while placebo did not modify these parameters. LVMe (from 195 to 188 gm; P less than 0.01) and CSA (from 20.2 to 19.8 cm2; P less than 0.05) were reduced by nitrendipine, which also improved cardiac performance (ESV fell from 44 to 38 ml [P less than 0.001] and EF fell from 62% to 66% [P less than 0.01]). No effect was observed in the placebo group. Our results indicate that nitrendipine is a powerful antihypertensive agent that also improves cardiac performance and slightly but significantly reduces left ventricular mass. PMID- 2931233 TI - Atriopeptins: volume regulatory hormones. PMID- 2931234 TI - Hypersensitivity vasculitis associated with streptokinase. PMID- 2931235 TI - Osteoarthritis as a public health problem. PMID- 2931236 TI - Influence of ATP and magnesium on phosphofructokinase from sea bass (Dicentrarchus labrax L.) liver. AB - Glycolytic enzyme phosphofructokinase (PFK) from sea-bass liver shows inhibition for ATP4- and MG-ATP2-, and ATP4- is a competitive inhibitor with respect to MG ATP2-. Free Mg2+ behaves as a mixed inhibitor on the kinetic with respect to the true enzyme substrate Mg-ATP2-, and eliminates the inhibition effect of this substrate. The kinetics with respect to Mg-ATP2- at non-inhibiting concentrations is not visibly affected by temperature of pH variation. The inhibiting effect of Mg-ATP2- is more marked at 22 and 10 degrees C (of three assayed temperatures 22, 15 and 10 degrees C and at physiological pH 6.8) as opposed to the maximum activity pH (8.0). PMID- 2931237 TI - Critical evaluation of quadratic logistic discriminant analysis methods: a case study. AB - Electrocardiographic measurements from two groups, patients with left ventricular hypertrophy and clinically normal cases, were analyzed to illustrate the performance of the linear logistic discrimination method in the case of very unequal covariance matrices. Two quadratic extensions of the linear model were critically investigated. The use of graphical methods to check the model has been stressed and illustrated. PMID- 2931238 TI - Evaluation of the protective value of an antisolvent gel by laser Doppler flowmetry and histology. AB - In a previous histological study, we observed the protective efficiency of an antisolvent gel (Antixol) against the skin irritation induced by epicutaneous application of n-hexane for 15 and 30 min. In the present study, we tried to evaluate the protective efficiency of the Antixol gel against the cutaneous irritation induced by the application of toluene for 10 min. The possible application of laser Doppler flowmetry as a new objective method to test skin irritation and to evaluate the protective efficiency of barrier creams and gels was confirmed by the histological findings. PMID- 2931239 TI - Ammonium persulphate sensitivity in hairdressers. AB - 12 of 49 professional hairdressers patch tested with ammonium persulphate gave positive reactions, in contrast to 1 of 118 patients who were not hairdressers. 7 out of 10 of these 12 patients have since given up hairdressing. The rate of degradation of ammonium persulphate in pet. and in aqueous solution was estimated, and found to be 24% in 6 months. PMID- 2931240 TI - Contact dermatitis to Butin-2-diol 1,4. PMID- 2931241 TI - Allergic contact dermatitis to nitrofurazone. PMID- 2931242 TI - Contact allergy to dexpanthenol. PMID- 2931243 TI - Contact dermatitis due to Centelase. PMID- 2931244 TI - Allergic cheilitis to azulene. PMID- 2931245 TI - Patch testing with barrier creams. PMID- 2931246 TI - Organic pigment as a cause of plastic glove dermatitis. PMID- 2931249 TI - Phosphorylated intermediates of two Ca++-ATPases in membrane preparations from lens epithelial cells. AB - By incubating preparations enriched in membranes from lens epithelial cells with [gamma 32P]-ATP and Ca++ at 0 degrees C for 15 seconds followed by SDS-PAGE analysis, it was possible to demonstrate a Ca++-dependent [32P]-phosphate incorporation in two polypeptides with Mr 105,000 and 140,000. Treatment of phosphorylated preparations with 0.06 N hydroxylamine at pH 5.4 and 25 degrees C removed the label from both polypeptides indicating that the phosphate was attached to the proteins by an anhydride linkage characteristic of the phosphorylated intermediates of the ATPases. Membrane preparations from sarcoplasmic reticulum and red blood cell studied under the same conditions showed a Ca++-dependent [32P]-phosphate incorporation into polypeptides with Mr 105,000 and 138,000, respectively, corresponding to the phosphorylated intermediates of the Ca++-ATPases present in these preparations. The results suggest the presence of two Ca++-ATPases in lens epithelial cells which, in terms of Mr, appear to be similar to those present in the sarcoplasmic reticulum and the red blood cell plasma membrane, respectively. PMID- 2931247 TI - A randomized cross-over comparison of two low-dose oral contraceptives upon hormonal and metabolic parameters: I. Effects upon sexual hormone levels. AB - The effect of a low-dose triphasic oral contraceptive (OC) containing ethinyl estradiol and levonorgestrel (EE/NG) upon serum levels of endogenous sexual hormones was compared to that of a preparation containing EE and desogestrel (EE/DG). Blood samples were taken on Day 6, 11, 21, and 28 of a control cycle and of the third cycle of treatment with either the EE/NG or EE/DG preparation (11 volunteers each). After a washout period of 3 months, the contraceptives were changed in a cross-over fashion. Blood samples were again taken on Day 6, 11, 21, and 28 of the third washout cycle and the third treatment cycle. There was no significant suppression of serum LH and FSH during treatment with EE/NG and EE/DG except on Day 21, while estradiol levels were significantly lowered. Similar to the gonadotropin concentrations, the estrogen levels showed great individual variations; although they were depressed in the majority of the women, there was a considerable stimulation of follicular activity in 36% of the women under EE/NG and 18% under EE/DG. Both EE/NG and EE/DG suppressed significantly serum progesterone, testosterone, and DHEA-S, while prolactin was unaffected. In three cases an escape ovulation seemed to have occurred, but no pregnancy was observed. The spottings (8/22 women) and breakthrough bleedings (6/22 women) did not correlate with the serum levels of estradiol. The results indicate that the suppression of gonadotropin secretion during treatment with low-dose OC is a time dependent process which in some women may be at or below the threshold of safe ovulation inhibition. PMID- 2931248 TI - Stimulation of the primary mixed leukocyte reaction. AB - This article will review the evidence that dendritic cells are specialized stimulator cells for the mixed leukocyte reaction. The topics to be considered are (1) identification of dendritic cells, (2) specialized stimulating capacity of dendritic cells in the allogeneic and syngeneic mixed leukocyte reactions, (3) stimulator cells for the secondary mixed leukocyte reaction, and (4) evidence for a role of dendritic cells during graft rejection in situ. PMID- 2931250 TI - Cytogenetics update for pediatricians. PMID- 2931251 TI - Differential susceptibility of BALB/c sublines to diabetes induction by multi dose streptozotocin treatment. PMID- 2931252 TI - Lymphocyte subpopulations of blood and alveolar lavage in blastomycosis. AB - Patients with blastomycosis were found to have differing lymphocyte populations depending on the extent of disease manifestations and whether or not therapy had been started. Patients with recovering pulmonary blastomycosis who had been receiving antifungal treatment for at least four weeks had lymphocyte subpopulations no different from control donors. Patients with treated extrapulmonary blastomycosis had similar T helper (TH) to T suppressor (TS) ratios compared to recovering pulmonary patients and control subjects; this ratio gives a false impression because extrapulmonary blastomycosis patients had a reduced absolute number of lymphocytes with either marker. In bronchoalveolar lavage fluid, pulmonary blastomycosis patients who were clinically improved while receiving antifungal therapy had fewer TH cells and a greater number of lymphocytes with the TS marker than did control subjects. Patients with pulmonary blastomycosis prior to therapy had a smaller TH/S ratio than the other groups in peripheral blood primarily due to a reduction in the circulating TH fraction in both absolute numbers of cells and in the percentage of total T lymphocytes. Pulmonary blastomycosis patients re-evaluated after at least four weeks of antifungal therapy had TH/S ratios that were similar to normal persons. This increase in TH lymphocytes corresponded to clinical improvement and in a temporal correlation to that described for the development of specific immunity in this illness. PMID- 2931253 TI - Giant readthrough transcription units at the histone loci on lampbrush chromosomes of the newt Notophthalmus. AB - We have studied transcription at the histone loci in oocytes of the newt Notophthalmus viridescens, using in situ hybridization of cloned probes to the nascent RNA on lampbrush chromosome loops. Clusters of the five histone coding sequences are separated by long tracts of a simple sequence DNA, satellite 1. We had previously demonstrated coordinate transcription of histone genes and satellite 1 sequences. We postulated that satellite sequences were transcribed by readthrough from histone gene promoters; that is, transcription initiated at any of the five usual promoters, but did not terminate at the 3' end of the gene. Instead transcription proceeded through downstream sequences in the histone cluster (including spacers and downstream histone genes), and then through the satellite 1 region. Our model led to several specific predictions, in particular that some internal spacer regions between the genes should be well represented in the RNA on loops, that certain sequences should be absent from the loops, and that presence or absence of particular sequences should be correlated with morphological polarity of the transcription unit. We have hybridized ten strand specific probes to the lamp-brush chromosomes and we find that the patterns of hybridization agree with the readthrough model of transcription. PMID- 2931254 TI - [Effusive-constrictive pericarditis: a radiologic study]. PMID- 2931255 TI - [Leakage of air in retrograde pneumopyelography (report of 42 cases)]. PMID- 2931256 TI - [Myelographic study of space-occupying lesions in the spinal canal]. PMID- 2931257 TI - [Investigation on the estimation of bone mineral content in vivo by radiographic methods]. PMID- 2931258 TI - [Roentgen study of bone changes in hemoglobinopathy]. PMID- 2931259 TI - [Radiologic approach of spondylolysis (an analysis of 200 cases)]. PMID- 2931260 TI - [X-ray diagnosis of primary leiomyosarcoma of the bone (report of five cases)]. PMID- 2931261 TI - [Corticosteroid-induced arthropathy (a report of 5 cases)]. PMID- 2931262 TI - Detection of distinct subpopulations of Langerhans cells by flow cytometry and sorting. AB - Flow cytometry was found to be a very appropriate tool for the study of Langerhans cells (LC), which represent a minor cell population (2-3%) of human epidermis, and allowed us to obtain new phenotypic, functional, and cell cycle data on these rare cells. The phenotypic analysis of cell surface antigens demonstrates the existence of two subpopulations of LC: the former is HLA-DR+ and OKT 6+ (about 90% of total HLA-DR+ cells) and the latter is HLA-DR+ and OKT 6- (about 10% of total HLA-DR+ cells). These subpopulations of LC are both able to stimulate the proliferation of peripheral blood lymphocytes (PBL) in the presence of keratinocytes i.e., in mixed skin lymphocyte reaction (MSLR). Analysis of the cell cycle could be performed on OKT 6+ LC. Results show that they can be found in the various phases of the cell cycle, suggesting that the large majority of Langerhans cells are able to proliferate in situ in normal human epidermis. PMID- 2931263 TI - [Population genetics analysis of the human electroencephalogram]. PMID- 2931264 TI - [Frequent occurrence of dyshidrosis-type eczemas of the hand caused by oil-in water emulsion in metalworkers]. AB - In a metal working enterprise, about 1/3 of the workers who had come into contact with a certain cutting solution, fell ill with an eczema of the hand in short time, the clinical aspect of which reminded a dyshidrosiform eczema of the hand. An epicutaneous test made with the emulsion oil-in-water had a negative result. After the cutting solution had been replaced by another product, the hand lesions disappeared rapidly. In the literature, we could not find any informations concerning dyshidrosiform eczemas of the hand, while manipulating emulsions oil in-water. However, a tendency to sudation of the hands is known. PMID- 2931265 TI - [Drugs in Poland: a review of literature on the symptoms of side effects]. AB - The present paper gives a review of the data published in Poland concerning side effects of drugs. The most numerous observations concern antibiotics (particularly penicillin), sulfonamides, salicylates and antitetanic serum. The most frequent complications were: shock, urticaria, erythema multiforme and exanthema maculopapulosum. PMID- 2931266 TI - [Treatment with topical corticosteroids in severe or resistant dermatoses]. AB - The efficacy and safety of betamethasone dipropionate glycol cream 0.05% and desoximetasone ointment 0.25% were compared in a randomized, double-blind study of 80 patients with resistant or severe corticosteroid-responsive dermatoses. Medication was applied to affected areas at a dosage of 3.5 grams twice daily for 14 days. In each treatment group, evaluation of efficacy was based on results in 35 patients and that of safety in 40 patients. Among betamethasone dipropionate glycol cream 0.05%-treated patients, signs and symptoms of dermatologic disease either cleared completely or markedly improved in 34/35 (97%). Comparable responses were observed in 31/35 (89%) patients treated with desoximetasone ointment 0.25%. Local tolerance to both study medications was excellent; no adverse reactions occurred. Plasma cortisol reduction occurred in few patients (4 resp. 3 patients each group), however this effect was only transient and reversible. PMID- 2931267 TI - [Metal contact eczema, a peculiar case in multiple occupational dermatoses]. PMID- 2931269 TI - [Increase of dehydroepiandrosterone sulfate and prolactin during plasmapheresis]. PMID- 2931268 TI - [The atrial natriuretic factor in severe congestive heart failure. Plasma level, hemodynamic, hormonal and renal effects]. AB - The effects of human alpha atrial natriuretic factor following bolus injection of increasing doses and during a continuous 30 minute infusion were investigated in 7 patients with severe congestive cardiac failure (NYHA III-IV). The natriuretic factor was measured in plasma before and after the bolus application or infusion. The plasma levels were raised in 6 patients. A significant inverse correlation was observed between the basal levels of the atrial factor and cardiac output. In addition, there was a dose-dependent fall in preload and afterload as well as in the peripheral vascular resistance and there was an improvement in cardiac performance. The alpha atrial natriuretic factor inhibited aldosterone and cortisol secretion and promoted diuresis and the urinary excretion of sodium and potassium. The plasma concentrations of renin, noradrenaline, vasopressin, 6-keto prostaglandin F1 alpha, the stable metabolite of prostacyclin, and prostaglandin E2 remained unchanged. PMID- 2931270 TI - [Pelvic inflammatory disease]. PMID- 2931271 TI - [Allergy and dentistry from the dermatologist's viewpoint]. PMID- 2931272 TI - [Characteristics of cells participating in the adoptive transfer of tumor associated suppressor activity]. AB - The application of a complex of methods for fractionation of mouse spleen cells with transplanted rhabdomyosarcomas has shown that optimal conditions for adoptive intravenous transfer of the tumour-associated suppressor activity are created under joint injection of the primed macrophages and lymphoid cells of spleen (from animals with the progressively growing tumours) interacting with the macrophages to syngenic recipients. PMID- 2931273 TI - [Monitoring of therapeutic neuroradiologic examination and therapeutic procedures using evoked potentials]. AB - Interventional neuroradiology makes use of different diagnostic and therapeutic catheterization techniques. Treatments performed are local intraarterial thrombolytic therapy, embolization and occlusion of brain supplying arteries, percutaneous transluminal angioplasty and intraarterial application of drugs. These treatments make it most important to check the patients neurological state during the procedure. Intraoperative monitoring of evoked potentials offers the opportunity to get objective information about changes in certain central nervous system functions even in anaesthesized patients. Usually intraoperative monitoring is performed to obtain information whether the function of structures at risk remains stable or is altered by the operation. This represents a more passive, observing way of monitoring. During interventional neuroradiology one is enabled to take additionally a more active and experimental way of monitoring by using the advantages of special catheter techniques like series of reversible balloon occlusion or intraarterial drug application. This leads to a dialogue between the radiologist and the neurophysiologist about the safety or the risk of the next step during a procedure. There are mainly two types of new information that can be achieved by active monitoring: the identification of functional territories of single or multiple feeding vessels and new insights into hemodynamics and the establishing of new sufficient collaterals. We have used intraoperative neuromonitoring in 35 patients during interventional neuroradiology. Our findings will be summarized and the usefulness of the different monitoring methods will be discussed. PMID- 2931274 TI - Steroid hormone levels in serum and skin receptor concentrations in hirsutism. AB - In 36 women androgen (AR), estrogen (ER) and progesterone (PgR) receptor were determined by dextran coated charcoal assay and subsequent Scatchard plot analysis in skin slices obtained from hirsute areas under local anesthesia. The biopsies were performed between day 18-21 of the menstrual cycle. Concomitantly venous blood was sampled in these and additional 14 patients for radioimmunoassay estimation of serum levels of testosterone (T), dehydroepiandrosterone sulfate (DHEA-S), androstenedione (A), estradiol (E2) and prolactin (PRL). However, it should be noted that all receptors and hormones were not examined in all patients. The incidence of ER-positive patients was smaller (i.e. 17%) than previous findings in acne and normal skin, while 26% of the examined patients were AR-positive. This result was similar to findings in acne, whereas the receptor levels are three times higher than in acne lesions. This suggests a greater androgen sensitivity of hirsute areas compared to acne lesions. Two out of 10 examined patients were PgR-positive. T was elevated in 63%, DHEA-S in 50% and A in 37% of examined patients. Lack of correlation between hormone serum levels and corresponding receptors concentration indicates a direct involvement of hormone action at the cellular level. The data combine to suggest that greater target organ sensitivity was responsible for hirsutism in those patients with normal androgen serum levels, while the absence of receptors in skin samples may characterize patients with idiopathic hirsutism. PMID- 2931275 TI - In vivo and in vitro effects of angiotensin II on the release of beta-endorphin like immunoreactivity. AB - The effect of angiotensin II (A II) on the release of beta-endorphin-like immunoreactivity (beta-END-LI) in rats was studied in vivo and in vitro. Intravenous injection of 1 microgram/100 g body weight of A II resulted in significant increase in the plasma beta-END-LI level after 10 and 20 min. Intraventricular injection of 1 ng/100 g body weight of A II also resulted in significant increase in the plasma beta-END-LI level after 10 min. A II at concentrations of 10(-12) M-10(-10) caused dose-dependent stimulation of beta-END LI release from dispersed cells of rat anterior pituitary. On gel chromatography, the beta-END-LI released by incubation of the cells with 10(-10) M A II separated into two components which eluted in the same positions as human beta-lipotropin and human beta-endorphin, respectively. The ratio of beta-LPH to beta-END in these fractions was 5:1 on a molar basis. A II did not stimulate beta-END-LI release in Ca++-free-medium. [Sar1, Ala8]-A II at concentrations of 10(-9) M - 10(-7) M did not stimulate beta-END-LI release from the cells. Addition of [Sar1, Ala8]-A II to the incubation medium inhibited A II-induced beta-END-LI release from the cells. These results indicate that A II acts, at least in part, directly on anterior pituitary cells to stimulate beta-END-LI release and that calcium ion is involved in the mechanism of this effect. PMID- 2931276 TI - Simultaneous determination of five androgens in early neonatal urine by selected ion monitoring GC-MS using 19-d3 steroids as internal standards. AB - Androgen levels in early neonatal urine were measured by GC-MS using trideuterated steroids at C-19 as internal standards. The deuterated steroid is not only stable in the process of analysis but also behaves chemically the same as the corresponding steroid to be measured so that the reliability in the method of analysis is satisfactory. The following results were obtained by this method: Androsterone levels in early neonatal urines were significantly higher in male than in female on the 1st, 3rd and 5th day, though the levels fell significantly from the 1st to 3rd day. Testosterone values were also higher in male than in female on the 1st, 3rd and 5th day. No sex difference in dehydroepiandrosterone or dihydrotestosterone was observed. The sex difference of the androgen levels indicated a testicular steroidogenesis in male neonates. PMID- 2931277 TI - Spectral and catalytical properties of the sarcoplasmic reticulum Ca-ATPase labeled with N-cyclohexyl-N'-(4-dimethylamino-1-naphthyl)-carbodiimide. AB - N-Cyclohexyl-N'-(dimethylamino)-carbodiimide (NCD-4) labels three sites in the sarcoplasmic reticulum Ca-ATPase which can be resolved by their spectral properties and by their effects on the catalytical activity of the enzyme. One site is not protectable by Ca2+ ions or by dicyclohexylcarbodiimide and is not essential for catalytical activity. Two Ca2+-protectable sites, whose modification leads to a biphasic inhibition of Ca-ATPase activity, have fluorescence emission maxima at 407 nm and 425 nm. The Ca-ATPase modified by NCD 4 hydrolyses ATP but does not translocate Ca2+ nor does it undergo the conformational changes associated with Ca2+ binding in the native enzyme. High concentrations of Ca2+ induce slow biphasic fluorescence quenching in the Ca ATPase labeled selectively at the 407-nm site but the signals are largely abolished by modification of the 425-nm site. Both vanadate ions and ATP reverse this Ca2+-induced fluorescence quenching. It is proposed that NCD-4 labels the two high-affinity Ca2+-binding sites of the Sarcoplasmic reticulum Ca-ATPase and that the conformational changes in the modified enzyme may reflect interactions between the two sites. PMID- 2931278 TI - Metabolism of thymoxamine. III. Structure elucidation of the metabolites and interspecies comparison. AB - The structures of six metabolites were elucidated using rat urine after intragastric administration of 14C-thymoxamine by means of enzyme incubations, mass spectrometry and synthesis of metabolites: desacetylthymoxamine, N-demethyl desacetylthymoxamine, the corresponding sulfates and glucuronides. The nature of the conjugates was confirmed by biosynthesis, i.e., co-administration of unlabelled thymoxamine and 35S-sulfate or 14C-glucose. The system high performance liquid chromatography-radioactivity detection was used for interspecies comparison. All biotransformation pathways are seen in rat and man. In dog and cat demethylation is a very minor reaction. Glucuronidation is not observed in the cat. PMID- 2931279 TI - Preliminary findings on calmodulin-stimulated Ca2+-ATPase of erythrocyte ghosts in psychotic patients. AB - Kinetic properties of the calmodulin-stimulated erythrocyte ghost Ca2+-ATPase seem to be altered in some sub-groups of affective and schizophrenic psychoses. The sub-group of affective disorders concerned mostly unipolar manic and bipolar psychoses with predominantly manic episodes. In the corresponding cases from schizophrenics hyper- and parakinetic basic syndromes were predominantly diagnosed. An evaluation of our preliminary results was undertaken in connection with our biochemical hypothesis on possible alterations in the regulation of Ca2+ concentrations and Ca2+-calmodulin-mediated processes under certain psychotic conditions. PMID- 2931280 TI - Effect of heparin and aspirin on platelet and clotting activation during leukapheresis. AB - Beta-thromboglobulin (beta TG), serotonin (5HT) and fibrinopeptide A (FPA) were assessed in twenty-two normal donors before, during, and at the end of leukapheresis. Seven procedures were carried out adding heparin to the circuit, and seven adding acetyl salicylic acid (ASA). The remaining eight procedures were carried out using only citrate and served as controls. Plasma beta TG increased both during and after the apheresis, together with a significant decrease of the intra-platelet content. Platelet 5HT did not show significant changes whereas FPA increased significantly. Using heparin, we obtained a complete prevention of FPA cleavage during the entire procedure, while beta TG increased at the middle of the procedure. No significant effects were observed using ASA both on beta TG and FPA levels. These features clearly indicate the activation of platelets and the thrombin generation in the apheresis circuit. Nevertheless, the activation of the clotting system seems to be predominant, as supported by the improved effect of heparin on beta TG and FPA amounts. PMID- 2931281 TI - Photoaffinity labeling and purification of solubilized D2 dopamine receptors. PMID- 2931282 TI - Renal and cardiovascular effects of acute and chronic administration of felodipine to SHR. AB - Renal function and salt and water turnover were studied in SHR during acute and chronic administration of felodipine, which is an efficient antihypertensive vasodilating Ca2+ antagonist. In conscious SHR acute administration of felodipine in hypotensive doses increased renal sympathetic nerve activity but caused renal vasodilation, increases in GFR and a 2-3 fold increase in urinary flow rate and sodium excretion. The fraction of filtered sodium excreted (FENa) was approximately doubled. The diuretic and natriuretic effects of felodipine are therefore suggested to be due to a direct inhibitory action on the renal tubular cells, resulting in reduced sodium reabsorption. Nifedipine also induced diuresis and natriuresis in this system, while minoxidil reduced water and sodium excretion. Throughout 6 months of felodipine treatment, the mean arterial pressure (MAP), remained 25-20 per cent reduced. Felodipine in combination with metoprolol reduced MAP 25-30 per cent and also caused regression of left ventricular hypertrophy, while felodipine alone prevented its further progression. Also during chronic administration, felodipine induced diuresis but had no effect on plasma volume and on sodium or potassium excretion in SHR. It is concluded that in SHR felodipine induces diuresis; on acute treatment this is secondary to reduced tubular sodium reabsorption, although during chronic treatment the sodium loss is compensated for while the diuresis remains. Thus, the cardiovascular and renal effects of Ca2+ antagonists like felodipine differ substantially from those of other potent antihypertensive vasodilators e.g. minoxidil. PMID- 2931283 TI - Behavioural stimulation is induced by separate dopamine D-1 and D-2 receptor sites in reserpine-pretreated but not in normal rats. AB - The dopamine (DA) D-1 agonist SK&F 38393 as well as the D-2 agonist pergolide and the mixed D-1/D-2 agonist apomorphine induced strong hypermotility and oral stereotypy in rats pretreated with a daily dose of reserpine for 2 and in particular for 4 days (3 and 5 injections, respectively). SK&F 38393 had no behavioural stimulant effect in saline-pretreated rats, whereas pergolide and apomorphine produced stimulation, although only after higher doses. Agonists at 5 HT and muscarinic receptors and at alpha 1-adrenoceptors were ineffective in reserpine-pretreated rats whereas the alpha 2-adrenoceptor agonist, clonidine, and the muscarinic antagonist, scopolamine, produced weak locomotor stimulation. The hypermotility induced by SK&F 38393 in reserpinized rats was blocked by pretreatment with the DA D-1 antagonists, SCH 23390 and SK&F 83566c, whereas the DA D-2 antagonists, YM 09151-2, clebopride and spiroperidol were weak or ineffective. In contrast pergolide-induced hypermotility was blocked by low doses of the D-2 antagonists but was weakly or not influenced by the D-1 antagonists. Selectivity ratios between drug potencies in the two models ranged from 65 to more than 600. The mixed D-1/D-2 antagonists, cis(Z)-flupentixol and cis(Z) clopenthixol, blocked the effect of both SK&F 38393 and pergolide. The alpha 1 adrenoceptor antagonist, prazosin, and the 5-HT2 receptor antagonist, ketanserin, did not modify the effect of SK&F 38393 or pergolide. Stereotyped behaviour induced by a high pergolide dose in normal rats was, in contrast to the effect in reserpinized rats, blocked by low doses of either SCH 23390 or spiroperidol. Finally, the hypermotility induced by apomorphine in reserpinized rats was markedly antagonized by both SCH 23390 and spiroperidol. The results suggest a close relation between D-1 and D-2 receptor sites in normal rats. After prolonged reserpine treatment, the D-1 agonist acquires full DA agonist efficacy. Furthermore, behavioural stimulation under these conditions is mediated by two separate D-1 and D-2 receptor sites which can be manipulated independently by antagonists. The mechanism by which this phenomenon occurs is unknown but the adaptational changes show close similarities to those observed after 6-hydroxyDA induced denervation. PMID- 2931284 TI - Effect of substances influencing brain serotonergic transmission on plasma vasopressin levels in the rat. AB - Studies were carried out in the rat to investigate whether serotonin (5-HT) is involved in the regulation of vasopressin (ADH) release. For this purpose plasma ADH levels were measured in rats treated with drugs enhancing 5-HT transmission, such as d-fenfluramine and quipazine and with 5-HT depleting drugs, p chlorophenylalanine (PCPA) and 5,7-dihydroxytryptamine (5,7-DHT). Forebrain 5HT, noradrenaline (NA) and dopamine (DA) were also measured. d-Fenfluramine and quipazine induced dose-related increases in plasma ADH levels in normohydrated rats. The effects of quipazine and d-fenfluramine were prevented by PCPA, indicating that 5-HT transmission was required for the biologic response. 5,7-DHT and PCPA pretreatment decreased forebrain 5-HT content and prevented ADH increases involved by water deprivation, suggesting that 5HT is necessary for the hormonal response to osmotic stimuli. The results summarized imply that serotonin may have a role in the physiological release of ADH from neurohypophysis. PMID- 2931285 TI - The effects of ketanserin, methysergide and LY 53857 on sympathetic nerve activity. AB - Preganglionic sympathetic nerve activity, blood pressure, heart rate and femoral arterial conductance were recorded in anaesthetised, paralysed cats. Three 5-HT2 antagonists, ketanserin, methysergide and LY 53857, were infused separately over 1 h periods. Ketanserin caused a fall in, methysergide a rise followed by a fall and LY 53857 only a rise in preganglionic sympathetic nerve activity. The sympathoexcitation caused by both LY 53857 and methysergide was not associated with any changes in blood pressure and heart rate. The sympathoinhibition caused by ketanserin and methysergide was accompanied by a fall in blood pressure and heart rate. Both ketanserin and LY 53857 caused increases in femoral arterial conductance, while methysergide caused a transient decrease. These differences are explained on the basis that ketanserin possesses alpha 1-adrenoceptor antagonist and methysergide 5-HT receptor agonist properties. It is suggested that 5-HT2 sympathoinhibitory receptors are involved in central cardiovascular control. PMID- 2931286 TI - Mechanisms involved in the vasodilator action of 5-hydroxytryptamine in the dog femoral arterial circulation in vivo. AB - The possibility that the vasodilator effect of 5-hydroxytryptamine (5-HT) in vivo involves a presynaptic inhibitory effect on sympathetic nerve activity was investigated in the femoral arterial circulation of pentobarbitone-anaesthetized dogs. The vasodilator effect of intraarterial (i.a.) 5-HT was abolished following ganglion blockade with mecamylamine, and remained inhibited after restoration of femoral vascular tone with i.a. ornipressin. These procedures had no effect on the vasodilator response to i.a. acetylcholine. The vasoconstrictor response to i.a. noradrenaline was not inhibited by mecamylamine. These findings suggest that a presynaptic inhibition of sympathetic neurotransmission is responsible for 5-HT induced vasodilatation in vivo. Pizotifen (0.1-0.4 mg/kg i.v.) inhibited the 5-HT dilator response, but the doses required were too high to be commensurate with an action at 'D' type 5-HT receptors. Ketanserin (0.1-0.4 mg/kg i.v.) specifically inhibited the dilator response to 5-HT; higher doses (1-4 mg/kg i.v.) also inhibited noradrenaline-induced vasoconstriction. Ketanserin, at all doses used, reduced systemic blood pressure and femoral vascular resistance. The effects of the lower doses of ketanserin (0.1-0.4 mg/kg) cannot be due to peripheral alpha adrenoceptor antagonism; blockade of the dilator effect of 5-HT may simply be due to inhibition of sympathetic nerve activity by ketanserin itself. PMID- 2931287 TI - Behavioral effects of morphine and phencyclidine in rats: the influence of repeated testing before and after single treatment. AB - Morphine-induced antinociception was determined in rats by using the hot plate procedure (56 degrees C). Two responses of the animals were analysed, i.e. the lick and the jump response. Repeated pre-exposure to the hot plate procedure shortly before morphine treatment augmented the efficacy of morphine to induce antinociception as measured by the lick response but markedly decreased the efficacy of this drug to lengthen the latency of the jump response in the same rat. The ED50 for intraperitoneally injected morphine increased from 1.7 (0.7 3.9) to 9.8 (6.5-14.7) mg/kg when rats were pre-exposed to the hot plate procedure and the latency of the jump response was measured. The slope of the dose-response curve was steeper after pre-exposure. Intraperitoneal or intravenous treatment with morphine markedly increased the latency of the jump response up to 3-4 h after injection, but only when rats were exposed twice or more to the hot plate procedure in the first hour(s) after injection. The effect of morphine was even present 24 h after injection. The maintenance of the morphine-induced effect is likely to have depended on opioids, since the effect disappeared after naloxone treatment. Phencyclidine induced a dose-related increase in locomotor activity (ED50: 0.97 (0.85-1.10) mg/kg) and in circling behavior (ED50: 1.02 (0.85-1.17) mg/kg) when the rats were tested 15 min after a subcutaneous injection. The effect of phencyclidine lasted longer when the rats were tested repeatedly after drug treatment, than when the rats were tested only once. This phenomenon was due to a decrease with time of the effects measured in the placebo-treated control rats repeatedly exposed to test procedure. The results demonstrate that repeated exposure to tests of behavior before and after treatment with psychoactive drugs markedly influences the behavioral action of these drugs. This has consequences for the determination of the efficacy and the time course of action of these drugs, especially when animals are exposed repeatedly to the test procedure in the absence or presence of the drug. PMID- 2931288 TI - An iodinated ligand identifying the D-1 dopamine receptor. AB - Iodination (with 125I) of SKF 83692 (2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3 benzazepin-7-ol) produces a ligand of high specific activity. In the caudate nucleus of rat brain, this ligand binds to a site which discriminates between the active and inactive enantiomers of drugs selective for the D-1 receptor but which does not recognize drugs selective for the D-2 dopamine receptor or a serotonin receptor. Non-specific binding of this ligand is less than 5% of the total binding. PMID- 2931289 TI - Presynaptic 5-HT autoreceptors on serotonergic cell bodies and/or dendrites but not terminals are of the 5-HT1A subtype. PMID- 2931290 TI - Morphine increases the activity of midbrain dopamine neurons in vitro. AB - Morphine produced a dose-dependent increase in the activity of dopamine containing neurons in the substantia nigra and ventral tegmental area recorded from mouse brain slices in vitro. The response was not changed in a low calcium/high magnesium incubation medium, indicating that the observed effects are the result of the direct action of morphine on dopamine neurons. Furthermore, a specific opiate antagonist, naloxone, reversed the excitatory effects of morphine in both brain regions, while naloxone alone had no significant effect on the activity of dopaminergic neurons. Morphine was more potent on ventral tegmental area than substantia nigra dopamine neurons. beta-Endorphin excited ventral tegmental area neurons but not substantia nigra cells, while [Leu5]enkephalin activated cells in both nuclei. These latter responses were blocked by naloxone. These data suggest that midbrain dopamine neurons contain receptors for opiates, and that ventral tegmental area neurons are more sensitive to the action of opiates than substantia nigra neurons. PMID- 2931291 TI - Effect of transition or heavy metals on [3H]haloperidol binding in rat striatal membranes in vitro. AB - Our previous experiments have shown that several metal cations affect dopaminergic uptake and release processes in synaptosomes in vitro. It is thus possible that other membrane-related steps of neurotransmission, such as receptor binding, are affected as well. We studied the effect of Mn2+, Cu2+, Cd2+, Zn2+, Hg2+, Pb2+ and of two organometals, methyl mercury and triethyl lead, on [3H]haloperidol binding in the striatal P2 fraction assuming that such a study would reveal direct effects of the ions on dopaminergic D2 receptor binding. According to non-linear curve fitting and Scatchard analysis, [3H]haloperidol bound to two sites in striatal tissue. The Kd of the higher affinity site was 0.14 +/- 0.05 nM and the Bmax 226.3 +/- 50.3 fmol/mg protein. The respective values for the lower affinity site were 2.49 +/- 0.56 nM and 678.3 +/- 111.4 fmol/mg protein. Among the divalent cations, Hg2+ (IC50 0.7 microM) and Cu2+ (IC50 2.9 microM) inhibited the high affinity [3H]haloperidol binding most potently. The inhibition by Cu2+ was due to a decrease in the binding affinity (increase in the Kd) while the number of binding sites remained unchanged. Zn2+ inhibited the binding by 41.8% and Cd2+ by 38.7% at 10 microM concentration while Pb2+ and Mn2+ did not affect binding significantly at this or lower concentrations. Methyl mercury (IC50 0.9 microM) and triethyl lead (IC50 2.6 microM) inhibited binding as well. Both these organometallic cations decreased the binding affinity but did not change significantly the number of binding sites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2931293 TI - Atrial natriuretic factor stimulates testosterone production by mouse interstitial cells. PMID- 2931292 TI - Solubilization of rat brain serotonin-S2 receptors using CHAPS/salt. AB - Serotonin-S2 receptors from rat frontal cortex were solubilized with a mixture of 6.8 mM CHAPS (3-[(3-cholamidopropyl)-dimethylammonio]-1-propane sulphonate) and 1.4 M sodium chloride. This new solubilization procedure solubilized about 40% of the membrane-bound serotonin-S2 receptors in an active form. The solubilized receptors were not sedimented after 1 h of centrifugation at 100 000 X g and they passed freely through 0.20 micron filters. The solubilized preparation showed high affinity binding of [3H]ketanserin and revealed a typical serotonin-S2 receptor profile: binding could be displaced by nanomolar concentrations of different serotonin antagonists and by micromolar concentrations of serotonin agonists. Compounds belonging to other pharmacological classes were poorly, or not active. Upon density gradient sedimentation, Svedberg coefficients of approximately 5 S were found on sucrose gradients made with H2O or D2O as the solvent. This was much lower than the value of 11.5 S previously reported from lysophosphatidylcholine-solubilized serotonin-S2 receptors. PMID- 2931294 TI - Changes in pituitary-adrenal function under extreme cold in DHA-treated persistent estrous rats. AB - The plasma corticosterone levels and incorporation of 14C-l-acetate into corticosterone and cortisol were measured in dehydroepiandrosterone (DHA)-treated persistent estrous rats and control estrous cyclic rats exposed to cold (-5 degrees C) for 12 hrs. Cold exposure significantly facilitated incorporation of 14C-l-acetate into corticosterone and cortisol in both DHA-treated and control rats. However, the rates of increase of plasma corticosterone level and 14C incorporation into corticosterone are 61% and 77% in controls, and 19% and 44% in DHA-treated rats, respectively. The activity of stress-induced pituitary-adrenal function showed masculine patterns in DHA-treated rats. The diurnal patterns of plasma corticosterone in DHA-treated rats are similar in controls. Plasma corticosterone levels in DHA-treated rats are evidently greater than those in controls. It is suggested that neonatal administration of DHA caused the changes not only in pituitary-gonadal system but also in pituitary-adrenal system. PMID- 2931295 TI - Influence of neurons on the occurrence of fibre types and myosin light chains in cultured presumptive slow and fast myoblasts. AB - Myoblasts from 9-day-old quail embryo slow anterior latissimus dorsi (ALD) and fast posterior and latissimus dorsi (PLD) muscles were co-cultured with neurons. The presence of neurons allowed ALD-derived muscle fibres to express characteristic features of a slow muscle (occurrence of alpha' and of beta' fibres and predominance of slow myosin light chains). On the contrary, PLD derived fibres did not differentiate into normal fast fibres (occurrence of alpha'-like fibres and absence of LC3f). These results are compared with the differentiation of ALD and PLD myoblasts in aneural condition. It is suggested that neurons can modify some phenotypic expression of presumptive slow or fast myoblasts. PMID- 2931296 TI - Coordinate expression of MnSOD and CuZnSOD in human fibroblasts. AB - The amount of manganese superoxide dismutase (MnSOD) and the activity of copper zinc superoxide dismutase (CuZnSOD) have been studied in five karyotypically normal human fibroblast strains, using nuclear magnetic resonance (NMR) and polarographic methods. A significant correlation between the two enzyme activities, and a linear increase of MnSOD with the increase of CuZnSOD have been demonstrated. Both enzymes are present in nuclei, mitochondria, lysosome microsome fraction and cytosol. These findings suggest that the two enzymes dismutate the O-2 cooperatively and that a common genetic control maintains the relative amounts of the two enzymes constant. PMID- 2931297 TI - NAD metabolism and mitogen stimulation of human lymphocytes. AB - The NAD concentration in eukaryotic cells is an important parameter for many aspects of metabolism including differentiation. As reported by other workers, the NAD content of resting human peripheral blood lymphocytes was low and increased dramatically over a period of 3 days after stimulation with the mitogen phytohemagglutinin (PHA). However, simultaneous measurement of the mean cell volumes showed that the average NAD concentration in fresh quiescent lymphocytes (401 +/- 128 microM) (SD, n = 7) was similar to that observed for other cell types. Furthermore, because of the increase in cell volume which occurred on mitogen stimulation, the NAD concentration in stimulated lymphocytes was only 2-3 fold higher than in fresh resting cells. This increase was also observed in lymphocytes incubated without mitogen and was apparently due to the level of NAD precursors in the culture medium and serum supplement. Hence, the NAD concentration in resting and stimulated lymphocytes is comparable to that of other eukaryotic cells and the variations in NAD content reported earlier have been widely misinterpreted. PMID- 2931298 TI - Relapse of host leukemic lymphoblasts following engraftment by an HLA-mismatched marrow transplant: mechanisms of escape from the "graft versus leukemia" effect. AB - Leukemic relapses and graft versus host disease (GvHD) remain major complications following allogeneic bone marrow transplantation for leukemia. We present clinical and laboratory details for an eight-year-old boy who received a T-cell depleted HLA-mismatched marrow transplant as therapy for acute lymphoblastic leukemia (ALL) in second remission. Engraftment with donor marrow was prompt and without any acute GvHD. Nevertheless, the patient's original ALL recurred and proved fatal. The patient remained a chimera with persistent donor lymphocytes present at the time of posttransplant relapse and subsequent to treatment with unsuccessful reinduction chemotherapy. In vitro immune studies showed that these leukemic cells could be recognized and destroyed by the donor's lymphocytes. The relapse itself suggests, however, that the donor's lymphocytes did not effectively destroy the patient's histoincompatible ALL cells in vivo following establishment of the chimeric state. Potential mechanisms are presented to account for this presumed "escape" from the postulated "graft versus leukemia" effect. PMID- 2931299 TI - Effect of activated lymphocytes on the regulation of hematopoiesis: suppression of in vitro granulopoiesis and erythropoiesis by OKT8+ Ia- T cells induced by concanavalin-A stimulation. AB - The effects of activated lymphocytes were studied in the regulation of in vitro hematopoiesis. Peripheral blood lymphocytes stimulated by concanavalin A (Con A) were cocultured with normal bone marrow cells in the assay system of hematopoietic stem cells. Con-A-stimulated lymphocytes and their supernatants showed significant suppression of in vitro growth of myeloid and erythroid progenitor cells (CFU-C, CFU-E, and BFU-E). Suppressive activity detected in the T-cell fraction was completely abolished by treatment with OKT3 or OKT8 monoclonal antibody and complement and 20 Gy radiation but not OKT4 or OKIa1 antibody and complement. These observations indicate that peripheral blood lymphocytes can be induced by Con-A stimulation to become suppressor T cells for myeloid and erythroid progenitor cells that are OKT8 positive, Ia negative, and radiosensitive. Together with our previous observation that CFU-C suppressor cells induced by alloantigen stimulation are radioresistant and OKT8- and Ia positive T cells, it is suggested that in vitro hematopoiesis may be regulated by heterogeneous subpopulations of activated T-lymphocytes. PMID- 2931300 TI - Blood flow in rat sciatic nerve during hypotension. AB - Laser Doppler flowmetry was utilized to examine blood flow in sciatic nerves of barbiturate-anesthetized and of unanesthetized decerebrate rats, in response to hypotension induced by graded exsanguination or by graded clamping of the descending aorta. Continuous laser Doppler flowmetry signals decreased linearly with decreasing arterial blood pressure. In anesthetized as well as in unanesthetized rats, the signal approached zero at a systemic blood pressure of 14 mm Hg or less. The results do not demonstrate autoregulation of blood flow in the rat sciatic nerve during systemic hypotension. PMID- 2931301 TI - A noradrenergic component of quinolinic acid-induced seizures. AB - Unilateral application of the convulsant brain metabolite, quinolinic acid, to unanesthetized rats resulted in a transient dramatic decrease in norepinephrine levels (nadir -70% after 2 h) in both the injected and the contralateral hippocampus. Dose-response relationships and the temporal sequence of this effect indicated a close functional association between seizure events and the decrease in hippocampal norepinephrine content. Massive release of the inhibitory transmitter, norepinephrine, may thus constitute the brain's defensive response to quinolinic acid-induced seizures. PMID- 2931302 TI - Effect of testosterone on the kinetics of the development of suppressor cells in adjuvant arthritis. AB - The induction of unresponsiveness to mycobacterial adjuvant took a longer time in male DA rats than in female rats. A shift in the induction time of unresponsiveness in males toward the female type was brought about by castration, but could be reverted to the male type by the application of testosterone. The transfer study revealed that cells capable of preventing arthritis required a longer incubation time for their development in males than in females. This suggests that testosterone inhibits the development of suppressor cells in adjuvant arthritis. PMID- 2931303 TI - Metabolism of glomerular basement membrane in normal, hypophysectomized, and growth-hormone-treated diabetic rats. AB - The in vivo synthesis of the renal glomerular basement membrane (GBM) collagen was studied in normal, hypophysectomized (hypox), diabetic, and growth-hormone (GH)-treated diabetic rats, using tritiated proline (L[2,3,3H]proline) as a radioisotopic precursor. After the injection of tritiated proline, all groups of rats were sacrificed at various time intervals and the specific activities of proline and hydroxyproline of GBM were determined, the latter being used as a measure of GBM collagen synthesis. A significant decrease in both proline and hydroxyproline specific activities were observed in GBM of hypox rats at all periods of study. Administration of GH to hypox rats returned the GBM collagen synthesis to normal. Diabetic GBM had higher proline and hydroxyproline specific activities when compared to normal rats. Treatment of diabetic rats with GH for 10 days further increased both proline and hydroxyproline specific activities when compared either to diabetic or normal rats treated with GH. The activity of glucosyltransferase, an enzyme involved in the biosynthesis of the disaccharide unit of GBM collagen was found to be decreased in glomeruli of hypox rats. In contrast, the activity of N-acetyl-beta-glucosaminidase, a glycoprotein-degrading enzyme, was found to be significantly increased in hypox rats. GH treatment restored both enzyme activities to normal. The results of the present study show that GBM collagen synthesis is decreased in hypox rats and increased in diabetic rats. GH treatment not only normalized GBM collagen synthesis in hypox rats but also caused significant increase in diabetic rats. This suggests that the renal GBM metabolism is influenced by GH, and this may be of particular significance in view of GH involvement in diabetic microvascular complications. PMID- 2931304 TI - [Effect of diazepam and nicotinamide on convulsive activity of various types]. AB - Acute experiments on mice were made to investigate the anticonvulsant activity of diazepam and its combination with nicotinamide in experimental seizures induced by corazol, picrotoxin, bicucullin and thiosemicarbazide. It was shown that diazepam (0.2-1.6 mg/kg) produced a dose-dependent anticonvulsant effect in all models under study. Nicotinamide (250 mg/kg) substantially reduced the animals' lethality and seizure manifestations induced by picrotoxin and completely protected some of the animals from the bicucullin-induced seizures. Nicotinamide (250 mg/kg) potentiated the anticonvulsant effect of diazepam in all the experimental seizures under study. Micotinamide had a more pronounced effect in respect of the protection of the animals from tonic seizures as compared with clonic ones. The data suggest that the mechanisms of the anticonvulsant action of nicotinamide are mediated via the GABA-benzodiazepine receptor complex. PMID- 2931306 TI - [The tuberculosis prevention work of a health center]. PMID- 2931305 TI - Quinolinate inhibition of gluconeogenesis is dependent on cytosolic oxalacetate concentration. An explanation for the differential inhibition of lactate and pyruvate gluconeogenesis. AB - In isolated rat hepatocytes, the phosphoenolpyruvate carboxykinase (PEPCK) inhibitor, quinolinate decreased gluconeogenesis from lactate more than from pyruvate (78 vs 44%). Quinolinate inhibition of PEPCK has been reported to be competitive with oxalacetate (OAA), and therefore higher cytosolic OAA concentrations could be expected to alleviate quinolinate inhibition of PEPCK and hence reduce its effect on gluconeogenesis. With pyruvate as a carbon source, the cytosolic concentration of OAA was higher than with lactate (40 vs 9.7 microM). The levels of OAA were manipulated metabolically by adding asparagine (which provides more cytosolic OAA through the urea cycle) or oleate (which increases malate efflux from the mitochondria). In each of the 8 conditions studied, quinolinate inhibition of gluconeogenesis was inversely related to the levels of OAA in the cytosol. Quinolinate inhibition of asparagine gluconeogenesis was not due to a non-specific effect on urea synthesis. PMID- 2931307 TI - [Health control over dish-washing machines in public catering establishments]. PMID- 2931308 TI - The coexistence of the Fusarium mycotoxins nivalenol, deoxynivalenol and zearalenone in Korean cereals harvested in 1983. AB - A survey for the occurrence of nivalenol (NIV), deoxynivalenol (DON) and zearalenone (ZEN) in Korean cereals (totalling 53 samples) harvested in 1983, showed that 96%, 72% and 57% of the samples were contaminated with NIV, DON and ZEN, respectively. Average concentrations (micrograms/kg) in unpolished barley were 546 (NIV), 117 (DON) and 110 (ZEN), and those in polished barley were 130 (NIV) and 21 (DON). The ZEN levels were below the detection limit (1 microgram/kg). Malt, wheat and rye were also heavily contaminated with these Fusarium mycotoxins. The results of this survey show that Korean cereals harvested in 1983 were significantly contaminated with NIV, DON and ZEN, and the incidence and levels, where observed, are similar to those reported in Japan. PMID- 2931309 TI - [Genetic heterogeneity of psoriasis]. PMID- 2931310 TI - [Irritant dermatitis in female workers of a cheese-making dairy]. PMID- 2931311 TI - Differences in the tumoricidal activation of rat and mouse macrophages by endotoxins. AB - Conventional and specific pathogen-free rat resident peritoneal macrophages were lytic to tumor cells in the presence of endotoxins even when not elicited or not stimulated in vivo or in vitro. In contrast, conventional mouse resident peritoneal macrophages were not cytolytic in the presence of endotoxins. The induction by endotoxins of rat macrophage-mediated cytolysis was only obtained after the binding of tumor cells by macrophages. Rat resident peritoneal macrophages bound faster and stronger to tumor cells than mouse resident peritoneal macrophages. These differences in binding could explain the species differences in the tumoricidal response to endotoxins. PMID- 2931312 TI - A general practice study investigating the effect of Minocin 50 mg b.d. for 12 weeks in the treatment of acne vulgaris. AB - In a multicentre general practice open study, 338 acne sufferers were treated with Minocin 50 mg b.d. (254 for 12 weeks). A highly significant improvement trend (p less than 0.0001) was found following analysis of visual analogue scales measuring (i) severity of acne, (ii) area covered by acne, (iii) number of inflamed lesions, (iv) density of acne lesions. Over all, 79% of patients thought the therapy to be effective or very effective; 70% of patients continued on the same therapy after the study period. Mean first improvement was noted by the patients after 4 1/2 weeks of treatment. One hundred and twenty-two patients had taken prior oxytetracycline therapy, of these, ninety-four (77%) stopped oxytetracycline therapy because of lack of efficacy. After treatment of these oxytetracycline failures with Minocin, a highly significant improvement trend (p less than 0.0001) of acne was again seen. In this group, 75% of patients thought the Minocin therapy to be effective or very effective; 69% continued Minocin therapy after the study period. In all, 74% of patients having received prior oxytetracycline thought that Minocin therapy was better than their previous therapy. Ninety-three patients had received either no previous therapy or topical therapy alone. Once again Minocin treatment resulted in a highly significant improvement trend (p less than 0.0001) in the severity of acne. Seventy six (82%) of these patients thought that Minocin therapy was effective or very effective. A total of 73% of patients continued with Minocin therapy following the study period. Adverse events were noted in 6% of patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2931313 TI - Time course of the lymphopenia in BB rats. Relation to the onset of diabetes. AB - The spontaneously diabetic BB rat syndrome is associated with a marked lymphopenia, which affects all members of litters of diabetes-prone rats, and may be a necessary condition for the development of the disease. We assessed peripheral blood lymphocyte counts and subsets from birth to 66 days of age with a view to assessing the early time course. At birth, total numbers were decreased, as were total T-cells (monoclonal antibody W3/13+, with an even greater deficit in OX19+ cells), the helper/inducer subset (W3/25+), and the suppressor/cytotoxic subset (OX8+), but Ia+ (B, OX6+) cells were not reduced. There was a less-than-normal rise in these values with time, and a similar pattern was observed at 66 days. Rats followed thereafter to onset of diabetes showed no differences at 66 days that were predictive of subsequent diabetes development. Another set of rats studied at the same age and again at onset of diabetes showed no changes concurrent with diabetes onset. The data are consistent with a genetically determined defect in lymphocyte numbers that leads to a subnormal rise in circulating cells later in life, and may predispose to another unidentified factor responsible for precipitation of the beta cell cytotoxicity. PMID- 2931314 TI - Diabetes induced by streptozocin results in a decrease in immunoreactive beta endorphin levels in the pituitary and hypothalamus of female rats. AB - Immunoreactive beta-endorphin (IR-BE) was measured by radioimmunoassay in the anterior pituitary (AP), neurointermediate lobe of the pituitary (NIL), and hypothalamus of female rats 4 wk after being made diabetic by a single injection of streptozocin (STZ). STZ-induced diabetes resulted in a significant reduction in the content and concentration of IR-BE in the AP and the content of IR-BE in the hypothalamus. Total hypothalamic protein was also significantly diminished. IR-BE levels in the NIL were unchanged. Column chromatography indicated that the reduction in IR-BE in the AP of the diabetic female rats represented a decrease in peptides that co-eluted with beta-endorphin and beta-lipotropin. In the hypothalamus, the reduction in IR-BE was represented solely by a decrease in a peptide co-eluting with beta-endorphin. Beta-lipotropin was not detectable in the hypothalami of control or diabetic female rats. These results suggest that, in the rat, diabetes may produce alterations in the mechanism(s) that regulate endogenous opiate levels in the pituitary and hypothalamus. PMID- 2931315 TI - The influence of T-lymphocyte precursor cells and thymus grafts on the cellular immunodeficiencies of the BB rat. AB - To determine whether abnormal T-lymphocyte precursor cells or an abnormal thymus is responsible for the immunologic deficiencies of spontaneously diabetic BB rats, thymus grafts or T-cell-depleted bone marrow cells were exchanged between diabetes-prone and non-diabetes-prone animals. Analysis of peripheral lymphocyte populations from these recipients with monoclonal antibodies, a fluorescence activated cell sorter, and mixed lymphocyte culture tests indicate that an abnormal thymus is not responsible for the immunodeficiency of BB rats, but that the defect resides within the lymphocyte precursor pool. PMID- 2931316 TI - Biochemical specificity of Xenopus notochord. AB - The biochemical composition and biosynthetic activity of Xenopus notochord were examined and compared with those of chick and mouse notochord. The notochords of all three species contain type-II collagen, and the notochords of Xenopus and chick synthesize a soluble glycoprotein with a molecular mass of 86 kilodaltons (kd). Mouse embryos were not tested for this molecule, because their notochords are too small to be dissected out. Most interestingly, Xenopus and chick notochords share a keratan-sulphate-containing proteoglycan which appears to be absent from mouse notochord. The presence or absence of keratan sulphate in the notochords of the different species reflects its presence or absence in cartilage. Since one role of the notochord in vivo is to stimulate chondrogenesis in the sclerotomes of the somites, this result provides support for the view that cells responding to the extracellular matrix produced by one tissue do so by increasing their production of the same matrix components. PMID- 2931317 TI - [Index of left ventricular hypertrophy in adolescents genetically predisposed to the development of arterial hypertension]. AB - Experimental studies on strains of normotensive rats genetically prone to hypertension and investigations on humans with borderline hypertension have shown an early involvement of the heart, mainly consisting in a trend to ventricular hypertrophy. To assess whether such alterations may preceed or follow the elevation of blood pressure, subjects who will develop hypertension, but whose blood pressure is currently normal must be studied. For this reason, we studied by means of M-mode echocardiography 51 normotensive males aged 14-19 years with family history for hypertension (at least one hypertensive parent; SHT). Fifty five normotensive subjects with both normotensive parents (SNT), matched for sex and age, were the controls. Average values of the following parameters were significantly higher in SHT than in SNT subjects: interventricular septum (5.4 +/ 0.8 versus 4.9 +/- 0.9 mm/m2; p less than 0.01) and posterior wall (5.4 +/- 1.1 versus 5.0 +/- 0.8 mm/m2; p less than 0.05) thickness, left ventricular mass (125.0 +/- 29.1 versus 109.2 +/- 25.4 g/m2; p less than 0.005) and cross sectional area (10.0 +/- 1.8 versus 8.9 +/- 1.6 cm2/m2; p less than 0.005). No significant difference between the two groups was observed in the indexes of left ventricular function. The existence of alterations of cardiac morphology in normotensive adolescents with genetic risk of hypertension shows that the cardiac involvement may preceed the development of high blood pressure. PMID- 2931318 TI - Electrocardiograms in hypertensive subjects from a population random sample: basic characteristics and correlations with some biological variables. AB - During the initial phase of the WHO "Community Control Programme of Hypertension" in Italy, 1,190 hypertensives (of both sexes, aged 20-64) were identified through the screnning of 5,856 people randomly selected from the whole population of the community of Camposampiero (Padova), and had a standard ECG tracing recorded. ECGs were all read according to the 2nd version of the Minnesota code (MC), by only one coder. First of all, the prevalence of the various items of MC in the two sexes was calculated. Absolutely normal ECGs (item 1-0) were found in 41.1% of the examined subjects; another 23.3% had only a shift of the transition zone to the right or to the left (items 9-4). Among pathological codes, the most frequent were those of class 3 relating to left ventricular hypertrophy (LVH) (i.e. 3:1 or 3:3) and those of classes 4, 5 and 7 relating to myocardial ischaemia (ISC) (i.e. 4:1-3 or 5:1-3 or 7-1). The overall frequencies of LVH and, respectively, of ISC (calculated by suitably grouping the above described items) were as follows. LVH: 21.3% in males (M), 14.6% in females (F); ISC: 5.7% in M, 18.1% in F. A significant (p less than 0.005) positive correlation with age was found both for LVH and ISC codes in F, only for ISC codes in M. A significant negative correlation between LVH codes and body mass index (BMI) was instead evident only in males.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2931319 TI - [Lack of correlation between HLA haplotypes and familial hypertrophic cardiomyopathy]. AB - In order to confirm the recent observations of the particular incidence of some HLA antigens in the familial hypertrophic cardiomyopathy we have determined the HLA-A, B and C antigens in the components of a family with high prevalence of hypertrophic cardiomyopathy (10 males and 7 females, age from 10 to 75 years). Six patients were affected by the disease. In one case (sudden death) the diagnosis was established by necroscopy; in the other living subjects by the characteristic echocardiographic features after having ruled out the conditions which can result in secondary myocardial hypertrophy. HLA typing showed the A9, Bw35, Cw4 aplotype in 4 of the 5 living patients affected by hypertrophic cardiomyopathy (2 with obstruction). This aplotype however was not shared by the other patient and was found in one healthy member of the family. Two patients affected by hypertrophic cardiomyopathy without obstruction did not share any aplotype while the 2 subjects with obstructive hypertrophic cardiomyopathy had the same aplotype of a healthy member of the family. Accordingly the genetic study of this family does not allow to establish a steady correlation between hypertrophic cardiomyopathy and HLA aplotypes. PMID- 2931320 TI - "Where there's a will"--camping for elderly and disabled people. PMID- 2931321 TI - [W-mutagenesis in the bisulfite-treated lambda phage]. AB - Survival of phage lambda cI857 inactivated by bisulfite (pH 5.6, 37 degrees C) is higher (the dose modification factor approx. 1.2) and frequency of bisulfite induced c-mutations 2-4-fold lower on the lawn of the wild-type strain ung+, as compared to ung-1 mutant deficient in uracil-DNA glycosylase. Irradiation of host cells by a moderate UV dose inducing SOS repair system enhances the frequency of bisulfite-induced c-mutations 2-3-fold in the wild-type (ung+) host, but not in the ung-1 mutant. It is suggested that W-mutagenesis in bisulfite-treated lambda phage in the ung+ cells is due to SOS repair of apyrimidinic sites which are produced during excision of uracil residues, the products of cytosine deamination. PMID- 2931322 TI - A CII-responsive promoter within the Q gene of bacteriophage lambda. AB - A site within the phage lambda Q gene shares homology with the CII-activated promoters, pE and pI, and is oriented in the direction opposite to that of Q gene transcription. A DNA fragment containing this site can serve as a template for CII-activated transcription in vitro. To ask if this presumptive CII control site functions as a CII-activated promoter in vivo, a restriction fragment containing this promoter has been cloned on a plasmid so that synthesis of beta galactosidase will be under its control. When CII protein is supplied in trans from a compatible plasmid, this promoter, designated PaQ, is activated to produce beta-galactosidase. A promoter positioned within the Q gene which can be activated by CII protein to initiate transcription in an anti-sense direction should result in an interference with Q gene expression, enhancing CII regulation of late functions, and adding to the list of known CII controls on the lysogenic response. PMID- 2931323 TI - Differential expression of influenza N protein and neuraminidase antigenic determinants in Escherichia coli. AB - Two influenza gene products of similar size and codon usage have been expressed in Escherichia coli under control of the phage lambda pR promoter. The influenza N protein (NP) was expressed in its entirety after fusion to a short (12 amino acid) segment of the lambda cro gene product and constituted about 1-2% of total soluble cell protein after induction. By contrast, constructions using the full length neuraminidase (NA) gene failed to give rise to detectable amounts of NA antigen after fusion to either the 12 amino acid Cro peptide or after fusion to bacterial beta-galactosidase (beta gal). Rather, expression of NA antigenic determinants was only achieved after deletion of coding sequences at the 3' end of the beta gal-NA fusion construct such that the encoded protein precipitated within the cell. PMID- 2931324 TI - Dx and Tx of the elderly patient with atherosclerotic coronary heart disease. AB - Complications of MI occur in patients of all ages, but are more common in the elderly. Prevalent are atrial and ventricular dysrhythmias, papillary muscle dysfunction, pericarditis, congestive heart failure, atrioventricular block, cardiogenic shock, and myocardial rupture. Improved surgical techniques and methods of myocardial protection have reduced the perioperative mortality of coronary artery bypass surgery in older persons to an acceptable level. PMID- 2931325 TI - [Prevention of hypertension in workers in motor transport enterprises]. PMID- 2931326 TI - [Natural uranium content of human organs and excreta]. PMID- 2931327 TI - [Experience in organizing health and hygiene inspection over the performance of measures for protecting the atmosphere]. PMID- 2931328 TI - [Hygienic evaluation of working conditions, nutrition and health status of female workers on a dairy farm]. PMID- 2931329 TI - [Mineral metabolism in phosphorus-production workers receiving recommended and actual nutrition]. PMID- 2931330 TI - [Dynamics of various physiological indicators and the effect of holidays on the activity of restorative processes in operators in a petroleum refinery]. PMID- 2931331 TI - [Physiological and ergonomic evaluation of work of female molders in the plastics industry]. PMID- 2931332 TI - [Effect of professional-occupational factors on the cardiovascular system]. PMID- 2931333 TI - Hereditary protein S deficiency. AB - Protein S is a vitamin K-dependent plasma protein that serves as a cofactor of activated protein C(APC) in its inhibitory action on activated factor V and factor VIII and in its stimulation of fibrinolytic activity. In plasma, part of the protein S is complexed with the C4b-binding protein. Only the free protein S has APC cofactor activity. In our laboratory, 30 patients from 8 nonrelated families were detected that fulfilled the criteria of an isolated protein S deficiency. All patients were heterozygotes for the defect that is inherited as an autosomal-dominant disorder. Patients with a protein S deficiency were found to be at risk for the development of venous thrombotic disease at a relatively young age. PMID- 2931334 TI - Effects of low temperatures on larvae of the genus Trichinella. AB - We examined the effect of an exposure to -25 degrees C (for 8 days) on the histochemistry and the fine structure of 30-day-old Trichinella larvae from muscle fibres of the diaphragm. The larvae of T. pseudospiralis and T. nelsoni were either destroyed in the muscle fibres, dead, eosinophile, or were not found. The structureless mass of a degenerating, changed sarcoplasm was highly AIP active, and gave a weak positive reaction for SS-groups of proteins. The wall of the deformed capsule around T. nelsoni, and the cuticle of the larva, stained diffusely; it did not contain AM. In a few muscle fibres exposed to -25 degrees C, histochemical reactions of the capsule surrounding larvae of T. nativa and sometimes of larvae of T. spiralis, and reaction of the changed sarcoplasm, were similar to those of the controls. A few mobile larvae were isolated by digestion only from a diaphragm infected with T. nativa. Deterrent to a prolonged survival of larvae were the formation of ice crystals and a denaturation of proteins by which the sarcoplasm of the infected muscle fibre was changed gradually into both a plasmolytically and karyolytically altered mass. Degenerative changes in the fine structure of infected muscle fibres were demonstrated by the presence of "spheromembranous bodies" in the sarcoplasm resembling myeline formations observed after exposure to poisonous substances, e.g., colchicine. PMID- 2931335 TI - Zeranol--a 'nature-identical' oestrogen? AB - The use of implants of zeranol (alpha-zearalanol), a widely-used anabolic growth promoter, in food animals results in very low residues of this compound in the edible tissues. In comparison, residues of myco-oestrogens--specifically the beta resorcylic acid lactones (RALs) such as zearalenone and its metabolites--commonly found as contaminants of cereals are much greater. Zeranol, the RALs and their metabolites are all closely related chemically, sterically and biologically. The biological effects of these compounds on reproduction, oestrogenicity, teratogenicity, genotoxicity and carcinogenicity are compared. No toxicological effects have been reported that cannot be attributed to the oestrogenic character of these molecules. In comparison with oestradiol, zeranol and the related myco oestrogens are 100-1000 times less active hormonally. It is concluded that a likely no-observed-effect level (NOEL) for these compounds will be of the order of 0.05-0.1 mg/kg body weight/day. This would result in a safety margin greater than 500-fold between the expected dietary exposure to these compounds (considered together) and the likely NOEL. On the basis of exposure to zeranol alone, this margin of safety would increase to more than 35,000. PMID- 2931336 TI - Pathology of 6-aminonicotinamide toxicosis in the rabbit. AB - Daily doses of 6-aminonicotinamide (3-5 mg/kg) given by ip injection produced ataxia of the hind limbs progressing to an ascending paresis/paralysis, anorexia, diarrhoea and death in male and female New Zealand White and Dutch Belted rabbits. At autopsy, caecal and gastric distention were seen and the apex of the gall bladder had necrotic foci. Light microscopic lesions included atrophy and necrosis of the white lobe of Harder's gland and atrophy of seminiferous tubules with cellular necrosis, vacuolation and the presence of multinucleated giant cells. Cytoplasmic vacuolation was observed in epithelial cells from many tissues, usually in the basal portion of the cells. Vacuolation of the epithelium of the sacculus rotundus and vermiform appendix was found within the same time frame as histiocytic hyperplasia in these organs. Spongiosis and gliosis were seen in certain parts of the central nervous system. Ultrastructural alterations in the gall bladder epithelium consisted of distention of intercellular space, mild distention of perinuclear space and coalescing, intracytoplasmic, membrane bound vacuoles, a few of which contained membranous debris. Some alterations of 6 aminonicotinamide toxicosis were prevented by simultaneous administration of nicotinamide with 6-aminonicotinamide. PMID- 2931337 TI - Population data on the forensic genetic markers: phosphoglucomutase-1, esterase D, erythrocyte acid phosphatase and glyoxylase I. AB - Blood specimens from white and black sample populations from Baltimore, Maryland, were analyzed for the four most forensically important, polymorphic red cell enzyme systems-phosphoglucomutase-1, esterase D, erythrocyte acid phosphatase and glyoxalase I. The distributions of the phenotypes for each marker in each racial group were in Hardy-Weinberg equilibrium. The population data were similar to previously reported data for Whites and Blacks from different geographical locations within the United States. PMID- 2931338 TI - [The future of the retinoids]. PMID- 2931340 TI - Caring for the sick from a sociological perspective. PMID- 2931339 TI - Myocardial imaging by digital subtraction angiography for left ventricular mass measurement. AB - Digital ECG- and respiration gated background subtraction and image combination were used to visualize the myocardial wall in routine left ventricular angiocardiography. Muscle mass was computed from manually traced biplane endo- and epicardial contours according to the multiple slices algorithm. Experimental validation and first clinical applications are reported. In animal experiments (13 pigs, 16 to 25 kg) a close correlation to postmortem measurement was found: r = 0.894 and SEE = 7.4 g for end-diastole, r = 0.938 and SEE = 6.2 g for end systole. The postmortem measurement was always within the 95%-confidence range of +/- 10%. In 16 patients (five days to 60 years, 3.2 to 81 kg) assessment of myocardial mass by myocardial imaging and conventional angiocardiography was compared. Conventional calculation based on manually outlined cavity contour and mean thickness of a lateral wall segment in the unprocessed angiogram. At end diastole myocardial imaging and the conventional method correlated closely with r = 0.986 and SEE = 18.7 g. Conventional mass determination was inaccurate in end systole (r = 0.928, SEE = 56.9 g) with values exceeding the diastolic ones by 26% +/- 19% (mean, SD), sometimes by up to 100%. Enclosure of the papillary muscle in the averaged wall segment probably leads to a mostly overrated mean wall thickness. There was no significant difference between diastolic and systolic results of myocardial imaging. In further investigations myocardial imaging showed good agreement to two-dimensional echocardiographic mass determination and, furthermore, has successfully been applied to study contraction pattern and to evaluate percentage of non-perfused muscle volume. PMID- 2931341 TI - Tuberculosis in Hong Kong. PMID- 2931342 TI - Immunisation. PMID- 2931343 TI - [Intestinal obstruction--Lodd's syndrome operation and appendectomy]. PMID- 2931344 TI - [How to recognize sleep deprivation in your ICU patient and what to do about it]. PMID- 2931345 TI - Single dose ciprofloxacin for treating gonococcal infections in men. AB - A single oral dose of ciprofloxacin 500 mg was used to treat five men with gonococcal urethritis and five men with gonococcal proctitis, and all were cured. In a subsequent study the dose of ciprofloxacin was reduced to 250 mg, and 54 men with 57 gonococcal infections (47 urethral, seven rectal, and three pharyngeal) were treated; of the isolates of Neisseria gonorrhoeae, four were penicillinase producing strains. All the patients were cured of gonococcal infection. Urethral specimens from nine of the men with gonococcal urethritis yielded Chlamydia trachomatis before treatment. These organisms were isolated again from all these patients seven days after treatment, and from a further seven men who had been chlamydia negative before treatment. It is concluded that a single oral dose of ciprofloxacin is an effective treatment for uncomplicated gonorrhoea, but is ineffective against C trachomatis. Of the 54 men given 250 mg ciprofloxacin, six (11%) showed minor abnormalities of liver function tests after treatment. PMID- 2931346 TI - Treating gonococcal infections resistant to penicillin in Bangkok: comparison of cefuroxime and spectinomycin. AB - Gonococcal organisms have become resistant to antimicrobials throughout the world. Such resistance is common in Thailand, where 40% of gonococci produce penicillinase (PPNG strains) and over half the remainder have MICs of penicillin greater than or equal to 1 mg/l. To evaluate the effectiveness of cefuroxime against such resistant organisms, a controlled clinical trial comparing spectinomycin and cefuroxime was conducted at Bangrak Hospital, Bangkok, in 1982 3. Of 472 patients who were randomly assigned to treatment, 365 (77%) yielded positive cultures before treatment and returned for follow up evaluation three to 13 days after treatment. Of the 365 patients, 359 (98%) were cured, and no difference between the two treatment regimens was found either by the sex of the patient or by the presence of PPNG strains. The MIC of cefuroxime against all organisms was less than or equal to 1 mg/l. In vitro susceptibilities of gonococci in Bangkok have not changed appreciably during the past two years. Regimens of cefuroxime and spectinomycin are highly effective even for the relatively resistant gonococci in Bangkok. The pharmacokinetics, in vitro susceptibilities, and effectiveness of cefuroxime encourage evaluation of lower doses of the drug. PMID- 2931347 TI - Chlamydial pelvic infection in cats: a model for the study of human pelvic inflammatory disease. AB - The inoculation of feline keratoconjunctivitis agent (Chlamydia psittaci) directly into the oviducts of eight cats produced an acute disease that was characterised by hyperaemia of the tissue and pronounced polymorphonuclear leucocyte infiltration of the epithelium and subepithelial stroma. The lumens of the tubes contained exudates of desquamated epithelial cells and polymorphonuclear leucocytes. After about 30 days the disease subsided leaving chronic inflammation with the tissue infiltrated with both polymorphonuclear and mononuclear cells. Fimbrial scarring and formation of adhesions were apparent by 40 to 50 days after inoculation. Chlamydiae were isolated in McCoy cell cultures from most cats, in one for as long as 51 days after inoculation. Inclusions were seen in histological sections or smears of cells from the fimbriae of four of the eight cats. Six of the eight cats developed antibodies to feline keratoconjunctivitis agent, which were detectable as early as 12 days after inoculation. To facilitate repeated examinations of the cats' fallopian tubes, techniques for laparoscopy in cats and for the collection of specimens while under laparoscopic examination were developed. The latter technique has since been applied successfully in man. PMID- 2931348 TI - Electrophoretic subtyping of phosphoglucomutase locus 1 (PGM1) polymorphism in the Italian and Czechoslovakian populations. AB - About 3,500 subjects from Italy and Czechoslovakia have been analyzed by acid starch gel electrophoresis for the subtyping of PGM1 polymorphism. The Italian sample included three different subgroups, from Northern, Central and Southern Italy. The allele frequencies found in the three groups do not differ significantly from each other; the observed values in the pooled sample are: PGM1S1 = 0.594, PGM1F1 = 0.118, PGM2S1 = 0.231, PGM2F1 = 0.057. In the Czechoslovakian group, which differs significantly from the Italian population, the following allele frequencies were found: PGM1S1 = 0.639, PGM1F1 = 0.118, PGM2S1 = 0.180, PGM2F1 = 0.063. The analysis of 217 families did not show any exception to Mendelian inheritance of the patterns. PMID- 2931349 TI - Antigen non-specific activities in culture supernatant of ovalbumin-specific, cloned helper T lymphoma. AB - Antigen non-specific activities in culture supernatants from clones of a radiation leukemia virus transformed, ovalbumin-specific helper T lymphoma were studied. After stimulation with ovalbumin-pulsed macrophages, these clones release factor(s) capable of providing carrier-specific help for anti-hapten antibody responses. It was found that in addition to IL 2-like activity, one clone constitutively released a suppressive factor that could inhibit polyclonal growth and differentiation of B cells stimulated with LPS. The factor inhibited activation of both syngeneic and allogeneic B cells directly, rather than via activation of accessory suppressor T lymphocytes. However, upon dilution of the supernatant, B cell growth and differentiation activities were detected. A role for a polyclonal B cell suppressor factor in the overall helper activity of the clone is proposed. PMID- 2931350 TI - Comparison of in vitro binding to enterocyte brush borders of rat IgG subclasses and their transmission in vivo in the rat. AB - The nature of the Fc receptors for IgG subclasses displayed on the epithelium of the small intestine in neonatal rats was examined by comparing results gained from 125I-IgG binding studies using isolated enterocyte brush borders, and from experiments where in vivo transmission from the gut to the bloodstream was quantified for each subclass. These measurements were made in two strains of rat, Cob Wistar and CB Hooded Nu/+. Subclasses of IgG were transported from gut to blood in different amounts, and the in vitro binding also varied according to isotype. Comparison of the results between rat strains and between isotypes suggested that at least two IgG Fc receptors are present on the enterocytes of the young rat. PMID- 2931351 TI - The expression of Fc and complement receptors in young, adult and aged mice. AB - Age-dependent changes in the expression of Fc receptors (FcR) for different isotypes of immunoglobulins and receptors for C3b, C5b and C3bi fragments of complement on the membranes of peritoneal macrophages were studied with mice of different ages. An age-related increase in expression of Fc receptors for IgM, IgE, IgA, IgG2b and IgG3, and a decrease in the expression of Fc receptors for IgG1 was observed. The expression of FcR on macrophages of donors of different ages corresponded with Fc-receptor mediated phagocytosis. The highest number of C3b-binding macrophages was found in aged mice, in contrast to low numbers of C3bi-binding macrophages at this age. The percentage of C5b-binding macrophages was lowest in adult animals. We also observed effective inhibition of binding of the C3b component of complement by preincubation of macrophages with aggregated IgG and vice versa. These observations suggest that fluctuation in expression of Fc but not C receptors may be important to the generalized changes that occur in macrophage function during development and ageing. PMID- 2931352 TI - T-cell control of IgA production. I. Distribution, activation conditions and culture of isotype-specific regulatory helper cells. AB - The capacity of T cells from different sites to augment IgA production by LPS stimulated B cells has been investigated. Peyer's patch T lymphocytes activated with Con A induced up to a 20-fold increase in IgA production. The effect was isotype-specific, in that no consistent effect on IgG and a diminution of IgM synthesis were observed. Less activity was recorded in spleen and mesenteric lymph node T cells. Optimal activation of the Thy 1+ Lyt 1+2- helper cells required the addition of splenic adherent cells and the elimination of Thy 1+ Lyt 2+ suppressor cells prior to activation. T lymphocytes maintained regulatory activity for several months after expansion in medium supplemented with IL-2 and are now being cloned. We conclude that IgA production is under control of T cells sited preferentially, but not exclusively, in gut-associated lymphoid tissue, and that these T cells can augment IgA production by B lymphocytes from sites with low commitment to production of this isotype. PMID- 2931353 TI - Lymphocyte function in experimental endemic syphilis of Syrian hamsters. AB - We have studied the changes in the lymph nodes, spleen and thymus that occur in inbred LSH Syrian hamsters infected with Treponema pallidum Bosnia A, the causative agent of endemic syphilis, as well as the B-cell responses of these infected animals to helper T-cell independent and dependent antigens. The lymph nodes increased significantly in weight up to 6 weeks after infection, and contained viable treponemes. No significant changes in the spleen weight were observed, and no viable treponemes could be recovered from the spleen. However, the size of the thymus decreased steadily during the course of the disease. The relative number of Ig+ cells (B cells) increased in the spleen and regional lymph nodes, whereas the relative number of T cells decreased during the course of infection. In both the spleen and lymph nodes, the relative number of macrophages increased initially and decreased thereafter in the form of a bell-shaped curve showing a peak at 4-6 weeks of infection. The ability of splenic lymphocytes from infected hamsters to mount a primary PFC response to pneumococcal polysaccharide type III (SIII), a helper T-cell independent antigen, was elevated throughout the course of infection. However, the splenic PFC response to sheep erythrocytes (SRBC), a helper T-cell dependent antigen, was increased only during the first 4 weeks of infection and progressively decreased thereafter. The PFC responses of infected lymph node lymphocytes to both SIII and SRBC were increased during the first 4 weeks and decreased thereafter. These data suggested that atrophy of the thymus seen in syphilitic infection is accompanied by the complex losses of subsets of T cells and altered B-cell functions. An early loss of suppressor T cells in both the lymph nodes and spleen occurs concomitantly with a loss of T helper cells and heterologous (treponema-unrelated) B-cell functions in the lymph nodes. Helper T cells are lost from the spleen only in the later stages of infection, whereas splenic B-cell functions remain intact throughout the course of the disease. These findings were further tested by in vitro methods where splenic and lymph node lymphocytes from infected hamsters were examined for their ability to respond to Con A in terms of the induction of antigen non-specific suppressor T cells. The mixing of Con A stimulated splenic or lymph node lymphocytes from infected hamsters was unable to inhibit the primary antibody responses of SRBC as compared to the normal control.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2931356 TI - Effect of cyclosporine and aminophylline on streptozotocin-induced diabetes in rats. AB - Diabetes induced in rats by multiple low doses of streptozotocin is thought to mimic type 1 disease in man. We tested the effect of concomitant treatment with immunomodulator drugs in this diabetic experimental model. Administration of cyclosporine resulted in a rapid appearance of hyperglycemia, perhaps by a potentiation of the direct cytotoxic action of streptozotocin on beta cells. By contrast, aminophylline administration protected the animals from the diabetogenic action of streptozotocin. Concomitant treatment with aminophylline and cyclosporine failed to protect the rats from the hyperglycemia induced by streptozotocin. PMID- 2931354 TI - T-suppressor clones derived from murine AMLR. AB - Panels of cloned T-cell lines were derived from the autologous mixed lymphocyte reactions of NZB and C58 mice. These clones were all Thy 1+. In addition, various clones expressed appropriate Ia, Lyt 1 and/or Lyt 2 antigenic specificities. None of these clones produced the lymphokines IL-2, CSF or AMLR-helper factor. The clones suppressed fresh syngeneic AMLR and MLR responses when added at low cell numbers at the initiation of culture. This suppression was not abrogated by treatment with mitomycin c or reversed by the addition of a source of T-cell growth factor. The mechanism of suppression was not cytotoxicity, as the clones were non-cytotoxic for either syngeneic or allogeneic cells. Many of the clones appeared to require the presence of Lyt 2+ cells in the MLR responding population to suppress, and therefore can be classified as T-suppressor inducers. Two clones did not require the Lyt 2+ subset to suppress the MLR, and are therefore T suppressor effectors. PMID- 2931355 TI - Effect of neuraminidase treatment on the expression of Fc IgG receptors on chicken embryonic bursa and thymus cells. AB - Bursa and thymus cells from chicken embryos at different ages were analyzed for Fc IgG receptors by EA-rosette technique and by binding of heat aggregated chicken IgG (agg IgG) in the indirect immunofluorescence test. Neuraminidase treatment resulted in a substantial increase of agg IgG binding cells both in the embryonic bursa and thymus. The binding of agg IgG was shown to be specific for Fc IgG receptors, since IgM and F(ab')2 fragments were not bound to neuraminidase treated embryonic cells. A far lower percentage of EA-rosette-forming cells than agg IgG binding cells were found both in untreated and neuraminidase-treated bursa and thymus cells. It was concluded that neuraminidase can reveal additional Fc IgG receptor sites mainly for agg IgG on embryonic thymus and bursa cells. PMID- 2931357 TI - Possible in vivo modulation of Leu 2a expression on suppressor T cells in active multiple sclerosis. AB - Reduced numbers of suppressor T lymphocytes were identified by monoclonal antibodies in the peripheral blood of patients with multiple sclerosis (MS) in acute relapse. In vitro culture of cells from these patients resulted in a significant increase in the number of cells identified with the suppressor T cell marker Leu 2a but not OKT 8. The expression of other T cell antigens (Leu 4 and Leu 3a) remained unchanged. This change in Leu 2a expression did not occur when cells from healthy controls were similarly treated. PMID- 2931358 TI - T-cell influence on the B-cell differentiation process induced by Klebsiella. AB - Klebsiella pneumoniae K43 cell membrane preparations (Klebs M) have been characterized previously as a human polyclonal B cell activator (PBA) that stimulates purified B cells to differentiate into immunoglobulin (Ig) secreting cells with negligible prior or parallel proliferation and in the absence of T cells. The aim of the present study was to define the cellular interactions in the regulation of Klebs M induced B-cell differentiation. For this purpose OKT4+ and OKT8+ cell populations were negatively selected with reasonable purity by means of a panning technique or by complement-mediated cytolysis using monoclonal OKT4 and OKT8 antibodies. The resulting cell populations were added to purified autologous B cells exposed to Klebs M or, as a control, pokeweed mitogen (PWM). In the Klebs M system both the OKT4+ and the OKT8+ cell subsets markedly enhanced IgM production; however, the helper effect of the OKT4+ cell subset was much more intense than that of the OKT8+ subset. In the PWM system only the OKT4+ cells provided help for B-cell differentiation. The OKT8+ subset demonstrated suppressor activity in the presence of an adequate helper cell (OKT4+ subset) function. These results indicate that Klebs M behaves like a "relatively T cell independent PBA". PMID- 2931361 TI - Effect of indomethacin and benoxaprofen on immune complex interaction with cultured glomerular cells. AB - Prostaglandins of the E series (PGE) increased immune complex (IC) interaction with cultured glomerular cells in a previous study. The present study examines the effect of indomethacin (IND) and benoxaprofen (BEN) on interaction of IC with cultured cells and their effect on PGE enhanced cell-IC interaction. IC were formed with antigen modified to produce a cationic (CAT) charge or left unmodified (UM). IND increased cell interaction with IC formed with CAT antigen (CAT IC). BEN had no effect on the interaction of IC formed with either antigen. The combined use of IND and PGE increased CAT IC interaction to the same degree as when each was used alone. BEN prevented the increased CAT IC interaction produced by IND or PGE when used in combination. Protamine sulfate prevented the enhanced CAT IC interaction produced by IND or PGE while sodium heparin had no effect. The results indicate IND and PGE increase cell IC interaction, the increase is not additive when they are combined, the effects of both are blocked by BEN, and protamine sulfate inhibits the effects of both compounds. PMID- 2931360 TI - Benign monoclonal gammopathy: a reassessment of the problem. AB - Disease associations of clonally restricted serum immunoglobulin (Ig) abnormalities were examined using methods for detecting and characterizing homogeneous Ig that are approximately forty times more sensitive than either cellulose acetate zone electrophoresis or immunoelectrophoresis. Medical records of three hundred five patients with clonally-restricted serum immunoglobulins, including 100 monoclonal gammopathies, and 205 immune complex/oligoclonal patterns were reviewed to obtain the attending physician's discharge diagnosis. Our data confirm lymphoproliferative disorders as the most frequent cause of monoclonal gammopathy (63% of our cases). However, in contrast to earlier reports, we found little evidence to support an association between monoclonal gammopathy and non-reticular malignancy. This does not mean our patients with these disorders had normal serum immunoglobulin patterns; rather, their qualitative abnormalities were, for the most part, not monoclonal. Instead, patients with these diseases had a high incidence of serum immune complexes and their antibody excess sequelae, oligoclonal patterns. Oligoclonal responses are noteworthy because Ig products of the individual clones do not always achieve equivalent serum concentrations, nor are the various clonal products synchronized with respect to the time at which they attain peak concentration. This creates a number of problems for laboratories attempting to characterize such abnormalities; 1) some analytical methods may only be capable of detecting the dominant clone of an oligoclonal pattern, and 2) analysis of a single specimen may yield erroneous results because the unique waxing and waning kinetic pattern of oligoclonal responses may preclude identification of all components at a single time point. We conclude that benign "monoclonal" gammopathies and circulating immune complex/oligoclonal Ig abnormalities occur in the same clinical situations and may be synonymous. The sensitivity of an individual laboratory's analytical methods would then determine which name is applied. PMID- 2931359 TI - L3T4 but not LFA-1 participates in antigen presentation by Ak-positive L-cell transformants. AB - We report that mouse L cells expressing Ak class II molecules on their surface after DNA-mediated gene transfer are capable of presenting the synthetic copolymer (Glu60 Ala30 Tyr10) to Ak-restricted long-term T-cell clones. Antigen induced T-cell stimulation could be inhibited by monoclonal antibodies (mAb) directed at spatially distinct determinants of the alpha and/or beta subunits of the Ak molecule, and by the rat L3T4-specific mAb H129.19. In contrast, several rat mAb reactive with the mouse LFA-1 molecule failed to inhibit T-cell activation when L cells were used as antigen-presenting cells (APC), although these mAb strongly inhibited the same T-cell responses in the presence of leukocytic APC. Similarly, the cytolytic activity of the Ak-specific T-cell clone A15.1.17 was blocked by L3T4-specific and by LFA-1-specific mAb when tested on Ak positive B-cell hybridomas, but only by L3T4-specific mAb and not by LFA-1 specific mAb when Ak-positive L-cell transformants were used as targets. These data support the notion that the LFA-1 molecule is not necessary for T-cell activation, and suggest that its functional role as an accessory molecule depends on the leukocytic nature of the APC tested. PMID- 2931362 TI - Immunosuppression by human seminal plasma. AB - Immunosuppressive property of normal human seminal plasma has been demonstrated on various in vitro immune parameters such as, blast transformation of lymphocytes with Phytohemagglutinin (P), Concanavalin A and Lipopolysaccharide, E & EAC rosette formation and mixed lymphocyte culture. The immunosuppression appears to be a T-cell mediated phenomenon. Analysis of semen samples obtained from 86 donors, comprising azoospermic, oligospermic, normospermic and polyspermic individuals, suggests that immunosuppression of the seminal plasma has no correlation with either the sperm density or the protein content of seminal plasma. The possible implication of the immunosuppressive activity in the development of acquired immuno-deficiency syndrome is also discussed. PMID- 2931364 TI - Long-term care insurance: the private sector leads the way. PMID- 2931365 TI - Doing well versus doing good. PMID- 2931366 TI - The effects of ownership and system affiliation on the economic performance of hospitals. AB - We investigated differences among five types of hospitals, defined by ownership (investor-owned or not-for-profit), system affiliation (system-affiliated or freestanding), and government sponsorship on 24 measures of economic performance. Using multivariate analysis of 1980 Medicare cost report and other data from a national sample of 561 hospitals, we found that investor-owned chain hospitals charged significantly more, and were more profitable, than all other types of hospitals except freestanding for-profits; there were no differences in productive efficiency that could be attributed to ownership or affiliation; the investor-owned hospitals had higher debt-to-asset ratios, less-capital-intensive plants, and greater capital costs as a percentage of operating costs than the not for-profits; and there were no consistent case-mix differences among the hospitals. PMID- 2931363 TI - Endotoxin tolerance diminishes certain antiinflammatory effects of endotoxin. AB - Endotoxin (bacterial lipopolysaccharide, LPS) is paradoxically both inflammatory and antiinflammatory. A single intravenous injection of 100 micrograms Escherichia coli LPS markedly inhibits the inflammatory changes associated with cutaneous reversed passive Arthus (RPA) reactions in New Zealand white rabbits. Polymorphonuclear (PMN) leukocytes from LPS-treated rabbits exhibit diminished responsiveness in vitro to complement (C5) -derived peptides. Repeated injections of LPS render animals "tolerant", that is, refractory to the toxic and inflammatory effects of LPS. We examined whether tolerance would enhance the ability of LPS to inhibit inflammation not attributable to LPS. Surprisingly, as compared with rabbits receiving a single dose of LPS, tolerant rabbits demonstrated greater inflammatory changes (i.e., PMN exudation, vascular permeability) associated with RPA reactions. PMNs from LPS-tolerant rabbits responded in vitro to C5-derived peptides significantly more than PMNs from rabbits that received a single dose of LPS. We speculate that some antiinflammatory effects of LPS require the toxic or inflammatory effects of LPS itself. These observations might relate to the limited efficacy of fever therapy and the variable effects of gram-negative sepsis on functions of human PMNs. PMID- 2931367 TI - Competing for Medi-Cal business: why hospitals did, and did not, get contracts. AB - Although we cannot yet judge the broad consequences of Medi-Cal selective contracting, we can assess the outcome of the contracting process and the role that competition and other factors played in that process. In this study of the qualitative and quantitative characteristics of hospitals in Los Angeles County that bid for Medi-Cal contracts, we analyzed the factors that were important determinants of whether or not hospitals received contracts. We found that hospital dependence on Medi-Cal inpatient revenues was most strongly associated with winning a contract and the presence of a teaching program next most strongly related. We discuss the relative importance of hospital need for a contract and the Medi-Cal special negotiator's desire to include certain hospitals in the program, and conclude with a discussion of our study's implications for competition and regulation methods in Medicaid cost containment strategies. PMID- 2931368 TI - Predicting hospital readmissions in the Medicare population. AB - Using a nationally random sample of Medicare beneficiaries, we developed a multivariate logistic model that identified a series of factors that predict readmission to an acute care hospital within 60 days of discharge. Our regression results show that 10 variables are statistically significant predictors of readmissions, with the patient's disease history and diagnosis among the best predictors. Our results can be used by peer review organizations to evaluate the quality of care provided by different hospitals as well as by physicians and social workers to improve discharge planning. PMID- 2931369 TI - The contribution of case-mix severity to the hospital cost-output relation. AB - Analyses of the cost-output relation of hospital care often omit diagnostic case mix from the analytic model. In this study, we examine the bias that arises from the use of either single-dimensional output volume or structural hospital capacity, but not case-mix severity, to analyze hospital costs and outputs. We found that hospitals with higher admission rates tend to admit less severe case mixes, other things equal, which implies that specialized facilities are relatively underutilized. Our finding provides a rationale for regionalization and sharing of costly specialized services and for reimbursement controls on the cost of capital. We conclude that public policy should focus on optimizing the mix of treatment services rather than on hospital size per se. PMID- 2931370 TI - The restructuring of U.S. health care. AB - Despite highly publicized recognition in the 1970s that a health care financing crisis existed in the United States, the crisis has gone unabated. In this review of the recent health care experience, I discuss the federal and other initiatives that were taken in the 1970s to curb health care cost increases and why they failed. I then review transformations that are currently altering the health care delivery and payment system in this country. I conclude with a discussion of three possible scenarios for the U.S. health care system at the end of the century. In the absence of a grass-roots acceptance of the limitations of medical intervention, it seems likely that total outlays will continue to increase. That is, we are probably in for "more of the same." PMID- 2931371 TI - The epidemiology of quality. AB - The quality of care can be perceived to have an "epidemiology" in that it is distributed in each of two populations, one of providers and another of clients. In this review of the pertinent literature, I found, overall, that the quality of technical care is better when practitioners have better or more training, are more specialized, and are more experienced though not too old; when they provide ambulatory care by appointment to a not overly large caseload in well-equipped premises and possibly in association with colleagues; and when they provide hospital care in larger institutions with significant teaching functions. I found no consistent correlation between quality and age, sex, rurality, occupation, income, and ethnicity of patients, but there were enough intimations of a relation between socioeconomic disadvantage and poorer technical care to prompt careful study. PMID- 2931372 TI - The impact of quality on cost in the provision of long-term care. AB - Regulatory and reimbursement policies in the health care industry have generally been developed on the assumption that a trade-off exists between quality enhancement and cost control. In this study of 494 proprietary, nonprofit, and government nursing home facilities in New York State, I examined the relationship between quality and costs while controlling for facility characteristics and resident characteristics. I found that although the capital-intensive aspects of patient care quality make a significant impact on costs, the labor-intensive aspects of patient care quality do not. I discuss the policy implications of these findings. PMID- 2931373 TI - The use of swing beds in rural hospitals. AB - The national program under which rural hospitals are currently providing swing bed care is the result of a HCFA-sponsored demonstration and evaluation program involving more than 100 rural hospitals in four states. We summarize herein the larger of two evaluation studies of the program. The experimental hospitals averaged approximately two fully occupied swing beds, experienced a 5% increase in total occupancy owing to swing-bed care, and may have reduced acute care length of stay slightly. A strong negative correlation between acute care occupancy and use of swing beds was observed, but no evidence was found to support the hypothesis that swing-bed care decreases nursing home occupancy in rural communities. PMID- 2931374 TI - A computer-aided system for planning acute care bed need in Michigan. AB - As part of an effort within Michigan to promote cost containment and equitably distribute hospital resources, the Acute Care Bed Need Methodology (ACBNM), a model for determining bed need based on normative use rates, was created. We describe herein the ACBNM, the associated interactive computer system, and the data base requirements, and make suggestions for improving the methodology. We also discuss the functions the ACBNM has served in Michigan and the role it could serve in future health planning efforts. PMID- 2931375 TI - Mapping of a cloned glucosyltransferase gene in Streptococcus mutans. AB - A cloned glucosyltransferase (gtfA) fragment, inserted adjacent to an erythromycin resistance (Eryr) marker in plasmid pVA891, was used in transformation experiments to determine the genetic location of gftA on the Streptococcus mutans chromosome. Eryr (gftA) cotransformed with a methionine (Met+) marker at a frequency of approximately 23%, whereas cotransfer with a number of other markers was not observed. The number of Met+ transformants was approximately 50-fold greater than the number of Eryr transformants. Furthermore, over 20% of the Eryr transformants were always Met+, whereas less than 1% of the Met+ transformants were Eryr, indicating the extreme asymmetrical cotransfer of these markers. The results indicate that S. mutans genes can be mapped by this procedure. PMID- 2931376 TI - Visceral leishmaniasis in congenic mice of susceptible and resistant phenotypes: immunosuppression by adherent spleen cells. AB - Visceral leishmaniasis is one of several parasitic diseases of humans characterized by immune suppression. A murine model of disseminated leishmaniasis utilizing inbred strains of specific genetic constitution was used to study the mechanisms of immunosuppression elicited during the course of infection. Resistant (Lshr) and susceptible (Lshs) strains of mice were challenged with amastigotes of Leishmania donovani and evaluated as to immune status at intervals between 2 and 40 weeks after challenge. The proliferative responses of splenic lymphocytes to T-cell mitogens, a B-cell mitogen, and parasite antigens were measured to evaluate the relative immune status of parasitized mice and noninfected control mice. Lymphocytes from resistant C3Heb/FeJ (C3H) mice responded normally to concanavalin A and phytohemagglutinin throughout the course of infection. Parasite antigen responses appeared 2 weeks after challenge of C3H mice and remained vigorous for periods up to 6 months. In contrast, immune suppression during infection was profound in both the curing (C57B1/10) and noncuring (B10.D2) phenotypes of Lshs congenic mice. Both Lshs strains developed severe infection as evidenced by high parasite burdens in the liver and spleen 4 to 5 weeks after challenge; splenic lymphocytes taken from these mice between 2 and 8 weeks became increasingly unresponsive to the T-cell mitogens as well as to parasite antigens. The noncuring B10.D2 mice which suffered chronic infection continued to be suppressed for as long as 40 weeks. C57B1/10 (curing) mice, in contrast, cleared infection between 12 and 16 weeks. After spontaneous recovery or elimination of parasites by antimonial drug therapy, the response of spleen cells to T-cell mitogens or parasite antigens were restored to normal. The spleen cells from the Lshs strains of mice obtained during the height of infection suppressed the proliferative responses of spleen cells from their uninfected counterparts upon cocultivation in vitro. Removal of adherent cells from the suppressive spleen cell populations restored normal mitogen responses. On the basis of adherence characteristics, phagocytosis, and morphology, the suppressor was identified as a macrophage population which appears to be responsible for a nonspecific immunosuppression of Lshs mice with significant parasite burdens of L. donovani. PMID- 2931377 TI - Visceral leishmaniasis in congenic mice of susceptible and resistant phenotypes: T-lymphocyte-mediated immunosuppression. AB - This paper continues a comparative study (A. D. Nickol and P. F. Bonventre, Infect. Immun. 50:160-168, 1985) describing immune responses exhibited by congenic, Lshs mouse strains C57B1/10 (cure) and B10.D2 (noncure) during the course of disseminated leishmaniasis. We report that sublethal whole-body irradiation of B10.D2 mice before challenge with Leishmania donovani converted the noncuring mice to a curing phenotype. Splenic lymphocytes from L. donovani infected B10.D2 mice failed to proliferate in response to parasite antigen stimulation in vitro. Splenic lymphocytes from irradiated, cured B10.D2 mice regained the capacity to respond to the parasite antigen stimulus. Transfer of T cells but not B cells from L. donovani-infected B10.D2 mice prevented the acquisition of immunity and recovery from infection in X-irradiated mice. In addition, a splenic T-cell population from L. donovani-infected B10.D2 mice suppressed the proliferation in vitro of parasite antigen-stimulated lymphocytes of irradiation-cured B10.D2 mice. Suppressor T cells were not demonstrable in the spleens of spontaneously cured C57B1/10 mice. Splenic lymphocytes from infected B10.D2 mice were deficient in the production of macrophage-activating factor (MAF) upon stimulation by L. donovani antigens in vitro. Deficient MAF production was specific for parasite antigen stimulation, because MAF production subsequent to concanavalin A stimulation of splenic lymphocytes from infected B10.D2 mice was not suppressed. The data suggest that a genetically based immunological defect in B10.D2 mice prevents the acquisition of effective cell-mediated immunity and subsequent elimination of L. donovani from tissue macrophages. The immunological deficit, not apparent in the curing C57B1/10, appears to be caused by the development of parasite antigen-specific suppressor T cells during the course of the disseminated leishmaniasis. PMID- 2931378 TI - Immunosuppression associated with the development of chronic infections with Rickettsia tsutsugamushi: adherent suppressor cell activity and macrophage activation. AB - Measures of general immunocompetency such as lymphocyte responses to mitogens and alloantigens and the ability to produce antibody to T-dependent and T-independent antigens were evaluated during the development of chronic infections with Rickettsia tsutsugamushi resulting from subcutaneous infection of BALB/c mice. It was found that a transient immunosuppression was demonstrable regardless of the infecting strain of rickettsiae; however, the immunosuppression produced by the Karp and Kato strains was more pronounced and longer lived. As a marked splenomegaly resulting from inflammatory macrophage influx accompanied this immunosuppression, mitogen- and antigen-induced lymphocyte proliferation was also evaluated after adherent cell depletion or in the presence of indomethacin, and both treatments significantly improved the responses. Isolated splenic macrophages were shown to suppress the responses of lymphocytes from naive mice as well as to exhibit parameters of activation including tumor cell cytolysis and cytostasis and the ability to inhibit the replication of R. tsutsugamushi in vitro. These data suggest an association between macrophage activation involved in rickettsial clearance and a transient immunosuppression. PMID- 2931379 TI - Evaluation of Bordetella bronchiseptica vaccines in specific-pathogen-free piglets with bacterial cell surface antigens in enzyme-linked immunosorbent assay. AB - The progenies of specific-pathogen-free sows which had been immunized with Bordetella bronchiseptica vaccines of various origin before parturition were challenged intranasally with B. bronchiseptica within 5 days of birth. Sera of piglets were taken weekly and investigated by enzyme-linked immunosorbent assay against a mixture of B. bronchiseptica cell surface antigens containing curled fibers and fimbriae, lipopolysaccharide, and a mixture of proteins mostly derived from the outer membrane. The serological response to this antigenic mixture was paradoxical; the highest titers were obtained with the least effective vaccines. Antibodies which did relate to protection were oriented against the outer membrane-derived proteins, one of which, of 68,000 molecular weight, appeared to be particularly important for two reasons. First, its concentration within the antigenic mixture was dependent upon cultural conditions; of all the proteins present in virulent strains, it was the first to disappear upon modulation. Second, it was absent from a strain which was unable to induce atrophic rhinitis in specific-pathogen-free piglets. Although all vaccines tested had some beneficial effect on the various clinical manifestations of the disease, only two vaccines were effective (P less than 0.001) in the prevention of nasal pathological changes. These two vaccines also stimulated the highest titers against the 68,000-molecular-weight protein. A mouse protection test utilizing a lethal intraperitoneal challenge failed to monitor the efficacy of vaccines for protection against atrophic rhinitis. PMID- 2931380 TI - Acquired resistance and expression of a protective humoral immune response in guinea pigs infected with Treponema pallidum Nichols. AB - Resistance to cutaneous syphilitic reinfection in strain 2 and strain 13 guinea pigs developed gradually 3 to 7 months after primary infection and reached maximum levels at 6 to 7 months after the induction of primary cutaneous disease. Associated with this acquired resistance was the occurrence of Arthus reactions and anamnestic-type antibody responses. Passive transfer of immune serum containing high-titered treponemal antibody into normal strain 2 guinea pigs significantly delayed the appearance and markedly diminished the severity and duration of skin lesions that developed after these recipients were challenged with treponemes but did not prevent the dissemination of organisms to the draining lymph nodes. These findings provide direct evidence that syphilitic infection elicits the formation of serum factors that are, at least, partially protective against symptomatic disease. PMID- 2931381 TI - Ciprofloxacin-induced hematuria. AB - We used ciprofloxacin, a quinolone-derivative, to treat a lung infection due to Pseudomonas aeruginosa in an adult cystic fibrosis patient. On three different occasions the use of ciprofloxacin was associated with the development of an asymptomatic hematuria with red blood cell casts. The mechanism responsible for this hematuria is presently unknown, but clinicians should be aware of this potential adverse effect of ciprofloxacin. PMID- 2931382 TI - In vitro activity of the newer quinolones compared with the classic ones and tobramycin. AB - The halogenated substitution of quinolone derivatives has given rise to a new group of substances called newer quinolones, which possess extraordinary antibacterial activity in vitro. The aim of our study was to compare the effect of the newer quinolones ciprofloxacin (CIP), norfloxacin (NOR) and enoxacin (ENO) with that of the classical ones nalidixic acid (NA), oxolinic acid (OX) and pipemidic acid (PIP) and with a widely-used aminoglycoside tobramycin (TBR). This was tested on 2,263 strains from clinical isolations. Evaluating the effect of the least active substances as a unit, we generally found the MIC90s to be of the following order: (Formula: see text). The remaining groups among the antibiotics studied are ordered identically, the most potent being the newer quinolones in the following order: CIP is at least four times superior to NOR, which in turn is at least twice as effective as ENO for gram-positive organisms, but only 1.2 times for gram-negative bacilli. PMID- 2931383 TI - Resistance of helper T lymphocytes to cyclophosphamide. AB - The effect of cyclophosphamide (Cy) on helper T lymphocytes using an adoptive transfer approach in athymic nude mice was investigated. The results indicated that Cy, at a dose (100 mg/kg) which virtually abolished anti-sheep erythrocyte (SRBC) antibody plaque forming cell (PFC) response of Balb/c mice, did not alter significantly the capacity of their splenic T cells to restore the anti-SRBC PFC response of nude mice. This resistance of T helper cells was observed in unimmunized mice and in mice injected with SRBC two days prior to Cy administration. It has been concluded that both resting and antigen stimulated T helper cells responsible for reconstituting anti-SRBC response of nude mice are resistant to Cy. PMID- 2931384 TI - A new immunomodulator, LF 1695--I. In vitro effects on the T lymphocyte lineage in man. AB - A new immunomodulator, LF 1695, was analyzed in vitro for its capacity to induce T cell markers (HTLA and OKT3, 4 and 8 antigens), to enhance the mitogen-induced lymphocyte proliferation, and to increase the Con A-induced suppressor activity. The inductive activity was compared with that of thymic hormone (thymosin fraction V). LF 1695 was capable of significantly augmenting the percentages of HTLA+ cells (10-15%) and of OKT 3+,T4+, or T8+ cells (13-28%) in human bone marrow prothymocytes. Maximum induction was observed at the concentration of 0.5 microgram/ml. In addition, LF 1695 significantly augmented the proliferation of human peripheral blood lymphocytes stimulated by mitogens (Concanavalin A, phytohemagglutinin, pokeweed mitogen and phorbol myristate acetate). LF 1695 also increased the Con A-induced suppressor activity of human lymphocytes. These data indicate that LF 1695 is active both on T cell precursors and on more mature T cells. PMID- 2931385 TI - Dose-response effects of 4-hydroperoxycyclophosphamide on human T and B cell function in vitro. AB - 4-Hydroperoxycyclophosphamide (4-OOH-CYP) is spontaneously converted in aqueous solution to 4-hydroxycyclophosphamide (4-OH-CYP), the major active metabolic of cyclophosphamide. We studied the dose related effects of in vitro treatment with 4-OOH-CYP on human T- and B cell-mediated immune responses. T-cell proliferation to mitogens and alloantigens was only partially inhibited even relatively high doses of 4-OOH-CYP (greater than 6-12 micrograms/ml). In contrast cytotoxic functions of activated T-cells and natural killer (NK) cells were inhibited at lower doses (3-6 micrograms/ml). PWM induced in vitro synthesis of IgG by B-cells was inhibited at less than 3 micrograms/ml of 4-OOH-CYP. These data indicate that 4-HOO-CYP has selective, dose-dependent effects on human T and B cells in vitro. PMID- 2931386 TI - Characteristics of histamine receptors present on suppressor T cells in "healthy individuals". AB - Twelve to 30% histamine receptor bearing cells were detectable in the peripheral blood mononuclear cells of healthy tuberculin sensitive individuals. The number of binding sites per cell ranged from 2.1 X 10(4) to 5.08 X 10(4) (mean 2.5 X 10(4)) with an affinity ranging from 2.5 X 10(-6) M to 10.9 X 10(-6) M (mean 3.6 X 10(-6) M). The histamine receptors on these cells were found to be of H2 type as indicated by the abrogation of binding of 3H-histamine by cimetidine. It was further confirmed that histamine receptor bearing cells in the peripheral blood belonged to a T cell subset which formed rosettes with AET treated sheep erythrocytes and had receptors for Fc portion of IgG and phenotype markers of T3 and T8. Deletion of such cells by means of affinity chromatography on histamine bound Sepharose columns, led to enhanced antigen induced lymphoproliferation indicating the suppressor nature of these T cells. PMID- 2931387 TI - Immunomodulation of allergic autocytotoxicity in bronchial asthma by a bacterial lysate--Broncho-Vaxom. AB - The direct and antibody-dependent allergic autocytotoxicity (ACT) response, mediated by food antigens and its immunoregulation with bacterial lysate of the eight most common pathogens of the upper respiratory tract--Broncho-Vaxom (BX), was investigated in fifteen bronchial asthma patients and eight normal control individuals. Under the described experimental conditions, the BX inhibits ACT response in vitro. In analyzing the mechanism of this effect, the enhancement of T suppressor cells by BX was under consideration. PMID- 2931388 TI - Immunosuppressive activity of prednisone and prednisolone and their metabolic interconversion in the mixed lymphocyte reaction. AB - The immunosuppressive activities of prednisolone, prednisone and cortisol were assessed and compared using a modified micro-2-way mixed lymphocyte reaction (MLR) assay. As measured by the inhibition of the MLR on day 3, prednisolone was 2.40 +/- 0.98 times more potent than cortisol: The average EC50S for prednisolone and cortisol were 28.25 +/- 7.8 ng/ml and 63.25 +/- 16.88 ng/ml, respectively. Prednisone (10 - 1000 ng/ml) had little or no immunosuppressive activity and did not affect the inhibition due to prednisolone or cortisol. Although, prednisone was inactive in the MLR, it was slowly being converted to prednisolone by 11 hydroxylation. MLR cultures with starting prednisone concentrations of 100, 200, 500, 1000 and 2000 ng/ml, contained 28, 34, 46, 50 and 81 ng/ml of prednisolone, respectively, on day 3 of the culturing period. The reverse reaction, the conversion of prednisolone to prednisone, did not occur. The inactivity of prednisone despite a significant conversion to its biologically active 11 hydroxyl metabolite, prednisolone, suggests the importance of the duration and timing of prednisolone's presence to immunosuppressive activity in the MLR culture. PMID- 2931389 TI - Concept of ergonomic and systematic work design for disabled workers. AB - Ergonomic work-place design for disabled persons contains the selection of work places appropriate for disabled, work-place design and work instruction and training. In order to support industry and administration in their activities of designing work-places for disabled workers a taxonomy of technical aids is presented taking into account the information most essential for practitioners. This classification is in accordance with the postulate of the ISO emphasizing the necessity for a classification of aids containing technical work aids as a main group. Therefore the classification system proposed should be considered as a frame work for a general taxonomy of technical aids at all. PMID- 2931390 TI - Early retirement in an international perspective II: The international study. AB - Initially this article describes the development of disability pension and early retirement in the ages of forty and up till ordinary pensionable ages in nine industrialized countries from the year of 1965 to 1980. During the period there are rising parts of the populations in these pension forms in the countries. The background of this development is, however, somewhat unclear. The following explaining factors are amongst others taken up in the article: A growing sickness, a rising unemployment and especially among the rather old an increased tendency to withdraw from the labor market (for example depending on better pension benefits). The two last mentioned factors are, however, more probable than the first one because of lower mortality rates in the countries under the studied period. Finally the article is concluded with an example of a preparatory suggestion to solve the involved problems in the now existing pension schemes by knitting the pension payments to more productive ages in the future. PMID- 2931391 TI - The sign of Leser-Trelat. A cutaneous marker for internal malignancy. PMID- 2931392 TI - Radiation-induced strand breaks in phi X174 replicative form DNA: an improved experimental and theoretical approach. AB - To determine the yield of radiation-induced single-strand, double-strand and potential breaks (breaks which are converted into actual breaks by alkali or heat treatment) oxygenated aqueous solutions of phi X174 supercoiled circular double stranded (RFI) DNA were irradiated with increasing doses of gamma-irradiation and subjected to electrophoresis on agarose gels both before and after heat treatment. A complete separation was obtained of RFI, RFII (relaxed circle due to one or more single-strand breaks) and RFIII (linear DNA due to one double-strand break). A computer-assisted spectrophotometric procedure was developed, which enabled us to measure very accurately the amount of DNA present in the three DNA fractions. The quantitative changes of each fraction of DNA with dose could be fitted to a straightforward statistical model, which described the dose-dependent formation of the different types of breaks and from which the D37-values of single-strand, potential single-strand and double-strand breaks could be calculated to be 0.42 +/- 0.02, 1.40 +/- 0.25 and 57 +/- 36 Gy respectively. Potential double-strand breaks were not formed significantly under our conditions. In addition the maximum distance between two independently introduced single-strand breaks in opposite strands resulting in a double-strand break could be determined. The values before and after heat treatment are shown to be 29 +/- 6 and 102 +/- 13 nucleotides, respectively. PMID- 2931393 TI - The effect of acute and chronic femoral artery ligation on the blood flow through the gastrocnemius muscle of the rat examined using laser Doppler flowmetry and xenon-133 clearance. AB - In this investigation the resting gastrocnemius muscle blood flow of the anaesthetized rat was evaluated using a recently developed laser Doppler flowmeter and the xenon-133 clearance technique. The perfusion of the microvasculature of the muscle was measured in normal control rats and in animals in which the supplying femoral artery had been acutely (1 h-1 week) or chronically (8-12 weeks) ligated. The laser Doppler flowmeter allowed continuous measurements of the muscle perfusion. Such measurements revealed a rhythmic fluctuation in the perfusion of the gastrocnemius muscle. The xenon-133 clearance technique did not allow continuous recording of muscle blood flow and rhythmical flow changes could not be observed. Acute ligation of the femoral artery reduced the mean muscle perfusion by 41% and 52% when assessed by laser Doppler flowmetry and xenon-133 clearance respectively. In comparison to animals without femoral artery ligation the hyperaemic response, following release of a tourniquet around the thigh or of an abdominal aortic occlusion, was markedly attenuated. Chronic ligation of the femoral artery reduced the mean muscle perfusion by 33% and 32% when assessed by laser Doppler flowmetry and xenon-133 clearance respectively. In these animals the hyperaemia, following tourniquet-induced muscle ischaemia, was reduced, compared to normal animals, but was more pronounced than observed in acutely ligated animals. In the chronically ligated animals abdominal aortic occlusion did not produce sustained muscle ischaemia and consequently no hyperaemic response was observed upon release of the aortic occlusion. We conclude that, as judged by the comparability of the results obtained using xenon 133 clearance, the laser Doppler flowmeter is a useful and sensitive new tool for the examination of the perfusion of tissue blood flow. The results suggest that chronic ligation of the rat femoral artery induces circulatory changes which mimic those seen in claudicants. PMID- 2931394 TI - Renal gallium accumulation in mice with acute immune complex glomerulonephritis. AB - 67Ga uptake and heparan sulfate (HS) content were investigated during the recovery of mouse kidney from acute immune complex glomerulonephritis induced by daily injections of bovine serum, and the binding of 67Ga to glomerular basement membrane (GBM) was studied in vitro. The results were as follows. 67Ga uptake in the kidney increased after the start of bovine serum injection, and peaked on the 20th day. The uronic acid content in 1.2 M NaCl-soluble fraction (which contained predominantly HS) and the hydroxyproline content (an index of collagen) were increased at the 10th day, reaching a maximum at the 20th day. This pattern of HS content was essentially the same as that of 67Ga accumulation in the kidney. Urinary protein and gamma-GTP activity peaked at the 5th day, and these patterns were different from that of 67Ga uptake. 67Ga binding to GBM was significantly inhibited by treatments with HS-degrading enzyme (heparitinase), nitrous acid, trypsin or papain. However, the binding to GBM was unaffected by treatment with chondroitinase ABC. These results provide further evidence that the 67Ga-binding substance in tumor tissues and inflammatory lesions is probably HS. PMID- 2931395 TI - Vesicular transport of newly synthesized opsin from the Golgi apparatus toward the rod outer segment. Ultrastructural immunocytochemical and autoradiographic evidence in Xenopus retinas. AB - Each day, rod photoreceptors of the vertebrate retina synthesize rhodopsin and insert it into new membranes of the rod outer segment (ROS). The authors determined which components of the rod cell transport opsin from the Golgi to the ROS by a combined EM autoradiographic and immunocytochemical study using radiolabeled amino acid precursors and antiopsin antibodies. Radiolabeled proteins in the ellipsoid region of Xenopus laevis retinal rods were localized by comparison of the distribution of silver grains with the predicted distribution generated by a hypothetical source: grain matrix. Sources of decay were not uniformly distributed. Small vesicles compressed between mitochondria and clustered beneath the connecting cilium that joins the inner to the outer segment contained more than 30% of the radiolabel and had a specific activity 17 times higher than the surrounding cytoplasm. Opsin was localized immunocytochemically on thin sections of retinas embedded in Lowicryl K4M (Polysciences; Warrington, PA) by reaction sequentially with biotinyl-rabbit antifrog opsin, biotinyl-sheep antirabbit F(ab')2, and avidin-ferritin. Golgi apparatus, intermitochondrial vesicles, and vesicles that clustered beneath the connecting cilium were prominently labeled. Subellipsoid smooth endoplasmic reticulum was labeled at background levels. These results demonstrate that intracellular vesicular membranes transport newly synthesized opsin from the Golgi to the base of the connecting cilium of X. laevis retinas. Antibody labeled the outer segment plasma membrane at a 10-fold greater density than the contiguous inner segment plasma membrane. The polarized distribution of opsin apparently involves not only vectorial transport of opsin in the inner segment but also restrictions to the randomization of opsin inserted into the inner and outer segment plasma membrane. PMID- 2931396 TI - Interventional cardiac catheterization. PMID- 2931397 TI - An introduction to the National Legal Center for the Medically Dependent & Disabled, Inc. PMID- 2931398 TI - The civil rights of handicapped infants: an Oklahoma "experiment". PMID- 2931399 TI - Supreme Court asked to review application of Rehabilitation Act to medical decisions. PMID- 2931400 TI - Effect of clonidine on plasma beta-endorphin, cortisol and growth hormone secretion in opiate-addicted subjects. AB - The effect of clonidine on plasma beta-endorphin, cortisol and growth hormone was studied in nine opiate-addicted subjects and seven control subjects aged 15 to 37 years. Clonidine, 0.15 mg, was administered orally in the morning, 18 to 24 h after the last administration of opioid drugs. Basal morning beta-endorphin levels were lower in the addicted than in the control subjects (3.76 +/- 0.8 vs. 7.42 +/- 1.2 pmol/l). Following the clonidine, there was an increase to normal values in the addicted subjects, but in the control subjects there was no change. Basal morning levels of cortisol were higher in the addicted subjects than in the controls (21.0 +/- 3.6 micrograms/dl vs. 13.0 +/- 1.2 microgram/dl, mean +/- SE). In control subjects clonidine induced a decrease of 50% in plasma cortisol, whereas in addicted subjects the decrease was not significant. It is hypothesized that in addicted subjects there is impaired activity of endogenous opioid peptides, leading to alteration in beta-endorphin and cortisol secretion. PMID- 2931401 TI - Helper and suppressor T cell subsets in 138 asthmatic children undergoing different therapeutic trials. PMID- 2931402 TI - The first year of a new young disabled unit. PMID- 2931403 TI - How does a day hospital work? PMID- 2931404 TI - [Porokeratosis plantaris, palmaris et disseminata]. AB - A 24-year-old female patient was treated for many years for "verrucae vulgares". Signs of porokeratosis were found by microscopy. Her medical history, the distribution of the hyperkeratotic-verruciform lesions and the characteristic histology features permitted the diagnosis to be made of porokeratosis plantaris, palmaris et disseminata. PMID- 2931405 TI - [Therapy of rhinophyma]. AB - Treatment of rhinophyma is successful only with surgical methods. The operative techniques described in the literature are discussed critically and decortication is the method of choice. When this technique is applied, the hyperplastic nasal tissue is removed down to the basal parts of the sebaceous glands. This causes spontaneous re-epithelization of the skin surface without scarring. Methods using deeper excision and plastic surgical repair of the defect by skin grafting or pedicled flaps are cosmetically inferior to the method of decortication. Whatever the method, however, histopathological examination of the excised rhinophyma tissue is necessary in order to exclude malignant growths, such as basal cell or squamous cell carcinomas, which are frequently seen in rhinophyma. PMID- 2931406 TI - [Porokeratosis plantaris, palmaris et disseminata]. AB - A 74-year-old patient has been affected for about 40 years by hardly discomforting keratotic lesions of the trunk and extremities, especially on the palms and soles. Some of his children and grandchildren have shown similar lesions. Histologically the diagnosis of porokeratosis was established by demonstration of a cornoid lamella. Clinically it appeared to be the rare form of porokeratosis plantaris, palmaris et disseminata, in which mainly the palms and soles are affected by hyperkeratotic papules, but nearly the whole body may be involved. It is discussed how this genodermatosis can be differentiated from other forms of porokeratosis. The family tree of our patient is compatible with autosomal dominant inheritance. PMID- 2931407 TI - Down's syndrome: decreased oxygen enhancement ratio in lymphocytes' DNA. PMID- 2931408 TI - Immuohistochemical demonstration of alpha-atrial natriretic plypeptide-containing neurons in the rat brain. AB - Using the immunoperoxidase technique in conjunction with specific antisera to alpha-atrial natriuretic polypeptide (alpha-ANP), it was shown that immunoreactive cell bodies and varicose fibers are widely distributed throughout the rat brain. The highest concentrations of alpha-ANP-containing neuronal cell bodies and fibers were found in the hypothalamus and septum. This result confirms the radioimmunological determination of alpha-ANP immunoreactivity in the rat brain. PMID- 2931409 TI - Histochemical and cytochemical demonstration of Ca++-ATPase activity in the stellate cells of the adenohypophysis of the guinea pig. AB - The histo- and cytochemical localization of Ca++-ATPase activity in the adenohypophysis of the guinea pig was studied utilizing a newly developed method (Ando et al. 1981). An intense reaction was observed in the wall of the blood vessels and between non-secretory cells (stellate cells) and endocrine cells of the pars distalis. Under the electron microscope the Ca++-ATPase reaction product was located extracellularly in relation to the plasmalemma of the stellate cells. This reaction was dependent on Ca++ and the substrate, ATP, and reduced by the addition of 0,1 mM quercetin to the standard incubation medium. Preheating of the sections before incubation completely inhibited the enzyme activity. When Mg++ in different concentrations were substituted for Ca++ in the incubation medium the reaction was always reduced. Both Ca++ and Mg++ in the incubation medium also reduced the reaction. The plasmalemma of the endocrine cells contains no demonstrable amount of Ca++-ATPase activity. The function of the Ca++-ATPase activity is discussed in relation to the regulation of the extracellular Ca++ concentration which seems to be important with respect not only to the secretory process of the endocrine cells but also to the metabolism of the adenohypophysis. PMID- 2931410 TI - Histochemical studies of Ca-ATPase, succinate and NAD+-dependent isocitrate dehydrogenases in the shell gland of laying Japanese quails: with special reference to calcium-transporting cells. AB - In order to elucidate the problem of which cells are involved in calcium transport and to estimate the role of mitochondria in calcium transport in the avian shell gland, the fine structure and the Ca-ATPase, succinate dehydrogenase (SDH) and nicotinamide adenine dinucleotide (NAD+)-dependent isocitrate dehydrogenase (NAD+-ICDH) activity of the shell gland of egg-laying Japanese quails were examined. The surface epithelial cells, consisting of ciliated cells with cilia and microvilli and non-ciliated cells with microvilli, had many large and electron-dense granules. The tubular-gland cells occupied the proprial layer and lacked secretory granules. When an egg was in the shell gland, the well developed mitochondria of tubular-gland cells characteristically tended to accumulate in the apical cytoplasm, while they were scattered throughout the cytoplasm when an egg was not in the shell gland. Intense Ca-ATPase activity was found on the microvilli of tubular-gland cells, and moderate activity was found on the lateral-cell surface. In the surface epithelial cells, the basolateral cell surface showed moderate enzymatic activity. Both SDH and NAD+-ICDH activity were found in tubular-gland cells when an egg was in the shell gland. These results strongly suggest that calcium for eggshell calcification is actively transported by the tubular-gland (depending on Ca-ATPase activity) and that the mitochondria of gland cells may play an important role in this process as an energy source. PMID- 2931411 TI - Evaluation of SR-2508 induced neurotoxicity and myotoxicity in rats using brainstem auditory evoked potentials and the posterior auricular muscle response. AB - Brainstem auditory evoked potential (BAEPs) and a middle latency component attributed to the posterior auricular muscle response (PAMR) to an intense auditory stimulus were used to measure the onset of neurotoxic and myotoxic effects in rats after chronic exposure to the radiosensitizer SR-2508. The rats received intraperitoneal injections of SR-2508, 500 mg/kg, 5 days/week for 6 weeks. BAEP and PAMR were measured after 10, 20, and 30 injections and 4 weeks after the drug treatment was stopped. A significant neurotoxic effect was observed: After 10 injections of SR-2508, latency of the fourth positive (P4) component of the BAEP, which is thought to represent activity from the superior olivary nuclei, increased from baseline levels, and a further increase was measured after 30 injections. Four weeks after drug treatment was stopped, P4 latency had not returned to baseline levels, indicating permanent injury. PAMR latency was also increased after 10 injections of SR-2508, but increased no further during the drug treatment period. Four weeks after the last injection, PAMR latencies had returned to pretreatment levels, indicating that the myotoxic effects of SR-2508 were reversible. PMID- 2931412 TI - Influence of cis-diamminedichloroplatinum (II) on mouse duodenal crypt stem cell survival after multifraction X ray treatment. AB - The mechanism of interaction of cis-platinum and X rays was investigated in mouse duodenal crypts using the microcolony assay. Mice were exposed to 1, 2, 5, 10, or 15 fractions of X rays, either alone or preceded by a single i.p. injection of cis-platinum, 8 mg/kg, one-half hour before the first fraction. In all fractionation regimens, cisplatinum caused a shift of the X ray survival curve for crypt cells towards lower doses. The vertical distances between the survival curves after X rays and those in combination with cis-platinum were about the same, giving a mean value of 0.89 +/- 0.12 log10 cells. After cis-platinum treatment alone, a crypt cell survival curve was established in the high dose range. The estimated cell kill by 8 mg/kg of cis-platinum, obtained by extrapolation of this curve, was 1 log10 cell number. These data imply independent cell killing mechanisms for cis-platinum and X rays. However, even after correction for cell kill by the drug, cis-platinum tended to inhibit slightly sublethal damage repair after X rays. This was supported by linear quadratic analyses, in which the alpha/beta value after combined treatment was found to be slightly higher than after X rays alone (20 +/- 4 Gy versus 13.0 +/- 1.7 Gy). PMID- 2931413 TI - A seven-day synchronization method for ewes using medroxyprogesterone acetate (MAP) and prostaglandin F2 alpha. AB - Estrous cycles of adult (n = 27), farm-flock, Suffolk ewes and Polypay range ewes (n = 224) were controlled with medroxyprogesterone acetate (MAP)-impregnated vaginal pessaries inserted (d 0) for 7 d in combination with prostaglandin F2 alpha (PGF2 alpha) injected on d 6. Descriptive criteria of the effects of this treatment regimen on endocrine characteristics of the estrous cycle were evaluated in the experiment with farm-flock ewes. The efficacy of this synchronization regimen on reproductive performance of range-bred ewes was tested in a second trial. Suffolk ewes bred at the second observed estrus after treatment to provide comparisons of cycle length between treated and control ewes. Polypay ewes were exposed to fertile rams at the controlled estrus. Eighty nine percent of Suffolk ewes were in estrus within 3 d after pessary removal. All nonsynchronized Suffolk ewes (n = 24) were in estrus over a 21-d period. Estrous cycle lengths of treated ewes averaged 16.8 +/- .2 d. Plasma progesterone concentrations were similar for treated and control ewes during the luteal phase of the estrous cycle. Ninety-one percent of the range-bred, controlled ewes lambed. Sixty-two percent of these ewes lambed within 150 d after exposure to fertile rams compared with only 17% of nonsynchronized ewes (P less than .05). Lambing percentage was similar by 167 d for treated (87%) or control (88%) ewes. Lambs per ewe exposed averaged 1.68 and 1.80 for treated and nonsynchronized groups, respectively. These data indicate the effectiveness of this 7-d treatment method for control of the estrous cycle of ewes during the normal breeding season. Results further show that this treatment scheme has practical application for range breeding of ewes. PMID- 2931414 TI - Uptake of ciprofloxacin by human neutrophils. AB - Ciprofloxacin was concentrated within human neutrophils to between four and seven times the extracellular concentration. Uptake was rapid and dependent on temperature, but not pH. The elution of ciprofloxacin from cells was equally rapid when the extracellular concentration was reduced. Intracellular ciprofloxacin was biologically active. It produced a significant reduction in viable counts of intracellular Staphylococcus, aureus in the presence of extracellular concentrations as low as 0.5 mg/l. The prior ingestion of Staph. aureus by neutrophils appeared to have no effect on ciprofloxacin uptake. PMID- 2931415 TI - The pharmacokinetics of ciprofloxacin in patients with impaired renal function. AB - Pharmacokinetics of ciprofloxacin after single oral administration of 250 mg were studied in patients with and without renal failure. Ciprofloxacin concentrations were measured by HPLC. The elimination half-life was 8.7 +/- 0.9 h (mean +/- S.E.M.) in six renal failure patients not on haemodialysis, as compared to 4.4 +/ 0.2 h in six patients with normal renal function. The urinary recovery of unchanged ciprofloxacin was 5.3 +/- 1.7% of dose over 24 h in the renal failure patients, as compared to 37.0 +/- 3.7% in the patients with normal renal function. In haemodialysis patients, the half-life was 5.8 +/- 0.9 h on an interdialysis day, and 3.2 +/- 0.4 h during haemodialysis. PMID- 2931416 TI - Management of lower gastrointestinal bleeding. PMID- 2931417 TI - The rigid ureteropyeloscope: description and applications. PMID- 2931418 TI - Lumbar spinal stenosis. PMID- 2931419 TI - Weight losers and gainers on seemingly identical diets. PMID- 2931420 TI - Edwin Bentley, M.D. PMID- 2931422 TI - Bacteriophages in L form of Staphylococcus aureus. AB - Lysogenicity and phage typability of Staphylococcus aureus L-form cells are described. Spontaneously produced phages were found in thin sections of S. aureus L colonies. The dimensions of the tail and head resemble those of the morphological group BIII2 (T. Krzywy, I. Durlakowa, A. Kucharewcz-Krukowska, S. Krynski, and S. Slopek, Zentralbl. Bakteriol. Mikrobiol. Hyg. Abt. 1 Orig. Reihe A 250:287-295, 1981). Phages 3A and 3C of the international typing set lysed both the bacillary and L form of S. aureus. PMID- 2931421 TI - Effect of inhaled procaterol hydrochloride in children with bronchial asthma, with particular reference to duration of effect. AB - This double-blind crossover trial evaluated the prolonged clinical effect of procaterol inhaled in a dose of 10 micrograms by nine asthmatic children with mild and stable respiratory disturbance. To compare procaterol with the placebo administered with a pressurized metered-dose inhaler 48 hr before or after procaterol, FVC, FEV1, V50, and V25 were followed up for 10 hr. FVC did not indicate a significant difference between the two treatments, while FEV1, V50, and V25 showed significantly greater changes after procaterol administration. The duration of action of procaterol in terms of FEV1, V50, and V25 was 6, 10, and 4 hr, respectively. PMID- 2931423 TI - Hyperphagia in premenstrual tension syndrome. AB - The relationship between premenstrual tension syndrome and dietary intake was studied in a population of 20 young adult women. Caloric intake was measured during the 10 days preceding and following the menstrual cycle. Those women with more severe symptoms recorded a greater increase in caloric intake. Caloric intake during the premenstrual period also increased with age. It is hypothesized that this caloric intake may be due to increased beta-endorphin levels. PMID- 2931424 TI - Two different preparations of subfragment-1 from scallop adductor myosin. AB - Chymotryptic digestion of scallop myosin yielded two different preparations of subfragment-1, having the following features. The major product from chymotryptic digestion of scallop myosin was subfragment-1 (S1) either in Ca-medium or in EDTA medium. However, the S1 preparations obtained from the digestion in Ca-medium, abbreviated as Ca-S1(CT), had both types of light chain subunits (regulatory light chains (R-LC) and essential light chains (SH-LC], and 100 Kdaltons (Kd) heavy chain subfragments (HCs), whereas the S1 preparations obtained from the digestion in EDTA-medium, ED-S1(CT), had no R-LC, partially fragmented SH-LC (SH LC), and 90 Kd HCs. On the other hand, Ca-S1(CT) and ED-S1(CT) were practically identical with each other in ATPase activity and in actin-binding ability. The two S1 preparations were also identical in that the Mg-ATPase activity of both S1 and acto-S1 was insensitive to calcium ions. Ca-S1(CT), which contained both R-LC and SH-LC in a stoichiometric amount, was further digested with trypsin, which is known to cleave rabbit skeletal myosin not only at the head-tail junction but also in the head. The tryptic digestion of Ca-S1(CT) appeared, in terms of the SDS-gel electrophoretic pattern, to occur at a much faster rate in Ca-medium than in EDTA-medium, and with a different digestion profile. It is therefore suggested that association of R-LC induces changes in the heavy chain conformation which result in an increase in the proteolytic digestibility of heavy chains and in an alteration of the site of proteolytic cleavage on heavy chains. PMID- 2931425 TI - Heavy meromyosin and subfragment-1 from squid mantle myosin, and Ca-sensitivity of their Mg-ATPases. AB - Heavy meromyosin (HMM) and subfragment-1 (S1) were obtained from squid mantle myosin by tryptic digestion and chymotryptic digestion, respectively. Squid HMM(T) and S1(CT) preparations contained stoichiometric amounts of the two types of light chain subunit; regulatory light chain, LC-2, and essential light chain, LC-1. No difference was detected in the chymotryptic digestibilities of squid mantle myosin in Ca-medium and in EDTA-medium. This is in contrast to the digestibility of scallop adductor myosin. The Mg-ATPase activity of HMM(T) alone and that of acto-HMM(T) were both sensitive to calcium ions. In contrast, the activity of S1(CT) alone and that of acto-S1(CT) were both insensitive to calcium ions. The affinity of HMM(T) for actin was not affected by calcium ions, but the amount of HMM(T) bound to actin was increased by calcium ions from 20% to 60% of the total amount of HMM(T). On the other hand, the actin affinity of S1(CT) and the amount of S1(CT) bound to actin were both unaffected by calcium ions. The role of calcium ions in the regulation of contraction in molluscan muscles is discussed. PMID- 2931426 TI - N-Iodoacetyl-N'-(5-sulfo-1-naphthyl)ethylenediamine modification of myosin from chicken gizzard. AB - Previously, we (Suzuki et al. (1978) J. Biochem. 84, 1529) reported that the sedimentation constant of chicken gizzard myosin in the presence of ATP was approximately 10S in 0.15 M or 0.2 M KCl and approximately 6S in 0.3 M or higher concentrations of KCl. The 10S-myosin and 6S-myosin were considerably different in conformation from each other. I now report the finding that the transformation of 6S-myosin to the 10S conformation results in a drastic change in the reactivity of thiol groups of gizzard myosin with N-iodoacetyl-N'-(5-sulfo-1 naphthyl)ethylenediamine (abbreviated as IAEDANS). The so-called SH1-type thiol groups (Sekine et al. (1962) J. Biol. Chem. 237, 2769) were present on 68 kilodalton fragments (produced by tryptic digestion) of gizzard myosin. The reactivity of the thiol groups with IAEDANS was greatly decreased by the 6S to 10S transformation of gizzard myosin molecules. Two other findings were obtained. Blocking the SH1-type thiol groups made the Mg-ATPase activities (in the presence of gizzard native tropomyosin) of gizzard myosin and of acto-gizzard myosin insensitive to calcium and to phosphorylation of regulatory light chains, although calcium-dependent phosphorylation of the IAEDANS-modified myosin could still occur. It also made gizzard myosin filaments resistant to the disassembly action of ATP. PMID- 2931427 TI - The role of calcium and Ca2+-ATPase in maintaining motility in ram spermatozoa. AB - Extracellular calcium at millimolar concentrations inhibits collective motility of ejaculated ram spermatozoa. In untreated cells, or when motility was made dependent upon glycolytic activity, there is very small inhibition, but when motility was made dependent upon mitochondrial respiration there is very high inhibition in motility by increasing extracellular Ca2+ concentration. Quercetin, which inhibits (Ca2+ + Mg2+)-ATPase activity in isolated plasma membranes, also inhibits motility mainly in cells that have been made dependent upon glycolytic activity, but there is also inhibition in untreated cells. When motility was made dependent upon mitochondrial activity, there is no inhibition but rather some stimulation in motility by quercetin. The inhibitory effect of quercetin is enhanced by increasing Ca2+ concentration in the medium. Quercetin also inhibits uptake of calcium into the cells, in a mechanism by which a calcium channel is involved. This inhibition is high only when the glycolysis is inhibited in the cells. The rate of glycolysis is decreased by quercetin or ouabain, but their effects on motility are quite different. Based on these data, it appears that the plasma membrane (Ca2+ + Mg2+)-ATPase or the Ca2+ pump have a functional role in the regulation of spermatozoa motility. This motility regulation is functioning through mechanisms which include glycolytic activity and maintenance of intracellular calcium concentrations. PMID- 2931428 TI - Sidedness of K+ activation of calcium transport in the reconstituted sarcoplasmic reticulum calcium pump. AB - Sidedness of the effect of K+ on Ca transport by the sarcoplasmic reticulum Ca pump reconstituted into soybean phospholipid vesicles was investigated. The reconstituted vesicles which sustained a high rate of Ca transport even in the absence of Ca-precipitating anions exhibited low passive permeabilities to 42K+, 86Rb+, or 45Ca2+. Evidence was presented that K+ activated the Ca pump on the external surface of the vesicles and that it was not taken up by the vesicles during the pump activity. In the presence of high externally added K+, the reconstituted vesicles preloaded with K+ exhibited a significantly higher Ca transport activity than the vesicles preloaded with Tris+ but not the ones preloaded with Li+. Ca transport by the K+-loaded vesicles was accompanied by a small amount of K+ efflux, which corresponded to about 20% of the amount of Ca+ taken up. Since the intravesicular K+ did not affect the turnover of the ADP insensitive component (E2P) of the phosphoenzyme intermediate formed during the pump cycle, it was concluded that the intravesicular K+ stimulated the Ca pump activity indirectly by compensating the charge imbalance caused by the electrogenic Ca2+ movement. These results thus indicate that K+ activates the Ca pump only on the cytoplasmic side of the sarcoplasmic reticulum membrane, but it is not obligately transported across the membrane under conditions where K+ fully activates the Ca pump. PMID- 2931429 TI - Crystallization of the Ca2+-ATPase of sarcoplasmic reticulum by calcium and lanthanide ions. AB - Two-dimensional crystalline arrays of Ca2+-ATPase molecules develop in sarcoplasmic reticulum vesicles exposed to Ca2+ or lanthanide ions. The Ca2+- or lanthanide-induced crystals are presumed to represent the E1 conformation of the Ca2+-ATPase, and their crystal form is clearly different from the earlier described E2 crystals induced by Na3VO4 in the presence of ethylene glycol bis(beta aminoethyl ether)-N,N,N',N'-tetraacetic acid (Taylor, K. A., Dux, L., and Martonosi, A. (1984) J. Mol. Biol. 174, 193-204). Analysis of the crystalline arrays by negative staining or freeze-fracture electron microscopy reveals obliquely oriented rows of particles corresponding to individual Ca2+-ATPase molecules. Computer analysis of the negatively stained lanthanide-induced crystalline Ca2+-ATPase arrays shows that the molecules are arranged in a P1 lattice. The pear-shaped profiles of Ca2+-ATPase molecules seen in projection in the density maps are similar to those seen in vanadate-induced crystals. The space group and unit cell dimensions of the E1 crystals are consistent with Ca2+ ATPase monomers as structural units, while the vanadate-induced E2 crystals form by lateral aggregation of chains of Ca2+-ATPase dimers. The transition between the E1 and E2 conformations may involve a shift in the monomer-oligomer equilibrium of the Ca2+-ATPase. The formation of E1 crystals by PrCl3 is promoted by inside negative membrane potential, presumably through stabilization of the E1 conformation of the enzyme. Cleavage of the Ca2+-ATPase by trypsin into two major fragments (A and B) did not interfere with the Ca2+- or the Pr3+-induced crystallization. PMID- 2931430 TI - Characterization of a third, cII-dependent, coordinately activated promoter on phage lambda involved in lysogenic development. AB - Lysogenic development by bacteriophage lambda is known to require the coordinate expression of two phage operons. Coordinate control is achieved by a positive regulatory mechanism which activates transcription from the promoters of these operons, PRE and PI. The positive effector is the phage regulatory protein cII. We now identify and characterize a third cII-dependent transcription unit on phage lambda, which is positioned in the middle of the Q regulatory gene and has an anti-Q orientation. We demonstrate the cII-dependent function of this promoter and precisely map its 5' transcription start-site both in vitro and in vivo. Most importantly, we show that cII binding and transcription activation at PaQ occur at essentially the same cII levels as those required for PRE and PI activation, and that all three promoters respond to cII at the same time following phage infection. In addition, DNase protection studies demonstrate that cII selectively interacts with the same TTGCN6TTGC DNA sequence repeat in the -35 region of PaQ which cII interacts with at both PRE and PI. We find that cII also binds other TTGCN6TTGC repeat sequences on lambda but binding at these sites does not lead to productive transcription. We conclude that PaQ functions in concert with PRE and PI to regulate the lysogenic growth response of phage lambda. We presume that the PaQ directed anti-sense Q RNA transcript functions to down-regulate the expression of the Q gene, which is needed for the expression of all phage late genes during lytic growth. PMID- 2931431 TI - Purification and characterization of a cation-dependent mannose 6-phosphate receptor from murine P388D1 macrophages and bovine liver. AB - A new binding protein which recognizes the phosphomannosyl recognition marker of lysosomal enzymes has been isolated from P388D1 macrophages which lack the 215 kDa Man-6-P receptor. This receptor was detergent-solubilized from total membranes and purified by chromatography on a lysosomal enzyme affinity column. An identical protein was purified from bovine liver using a two-step procedure which is based on the difference in ion requirement and ligand specificity of the new Man-6-P binding protein and the previously characterized 215-kDa Man-6-P receptor. After detergent solubilization of membranes, both receptors were co purified on a phosphomannan-Sepharose affinity column run in the presence of MnCl2 and then were separated using a Dictyostelium discoideum lysosomal enzyme Affi-Gel column which, in the absence of MnCl2, retains only the 215-kDa Man-6-P receptor. The new Man-6-P receptor binds efficiently to phosphomannosyl monoester containing ligands when MnCl2 is present. This binding is specifically inhibited by Man-6-P or by low pH. The cation-dependent Man-6-P receptor has a subunit molecular size of 46 kDa and appears to be an oligomer composed of three subunits. The receptor contains both high mannose (or hybrid)- and complex-type oligosaccharide units on the basis of sensitivity to digestion with endo-beta-N acetylglucosaminidase H and endo-beta-N-acetylglucosaminidase F. Radioimmunoassays carried out with two different antibodies demonstrate that the 46-kDa cation-dependent Man-6-P receptor and the 215-kDa cation-independent Man-6 P receptor not only differ in their properties but are also immunologically distinct. PMID- 2931432 TI - The role of ATP hydrolysis in the breakdown of proteins and peptides by protease La from Escherichia coli. AB - The energy requirement for protein breakdown in Escherichia coli appears to be due to protease La, the lon gene product, which hydrolyzes proteins and ATP in a coupled process. This novel enzyme was investigated with small peptides, identified as substrates in the preceding manuscript. Although the degradation of proteins to acid-soluble material requires hydrolysis of a nucleoside triphosphate, cleavage of small fluorogenic substrates, such as glutaryl-Ala-Ala Phe-methoxynaphthylamine, was found to require only binding of nucleotides to the enzyme. Nonhydrolyzable analogs of ATP, slowly hydrolyzed nucleotides, and even inorganic triphosphate and pyrophosphate stimulate the breakdown of these peptides but not of large proteins such as casein or serum albumin. In addition, vanadate, an inhibitor of the enzyme's ATPase activity, prevents protein degradation, but vanadate does not inhibit and can even stimulate peptide hydrolysis. Degradation of natural oligopeptides or of small polypeptides (less than 10,000 Da) also does not require hydrolysis of the nucleotide. Furthermore, although protein substrates promote ATP cleavage, the fluorogenic peptides inhibit this process. Also, no evidence was obtained for phosphorylation of the protease or of the substrate during ATP hydrolysis. These findings suggest that protein breakdown involves a cyclical series of reactions: 1) ATP binds to the protease and activates it allosterically, thus allowing peptide bond cleavage; 2) the hydrolysis of ATP must occur subsequently and should prevent further peptide bond cleavage until additional nucleoside triphosphates are bound; 3) with proteins as substrates, this reaction cycle probably occurs repeatedly until small peptides are generated. PMID- 2931433 TI - Mutational analysis of primosome assembly sites. Evidence for alternative DNA structures. AB - Primosome assembly sites are complex DNA structures that share common functions (they elicit the DNA-dependent ATPase of replication factor Y from Escherichia coli and serve as origins of complementary strand DNA synthesis), but display little sequence homology. In order to ascertain a common basis for factor Y-DNA recognition, a primosome assembly site and its mutated derivatives have been functionally and structurally analyzed. Under conditions in which they lose the capacity to function as ATPase effectors these DNA templates have been (i) assayed for their ability to bind factor Y, and (ii) probed, with pancreatic DNase, for structural alterations. In this ATPase-inactivating environment (suboptimal concentrations of MgCl2 and NaCl, and high levels of the E. coli single-stranded DNA binding protein), factor Y does not bind to its cognate DNA and the DNase cleavage pattern characteristic of this site is perceptibly changed: compared to the DNase digest obtained under activating conditions, cleavage is notably decreased in the 5' half of the site and enhanced at the 3' end. The results of this study strongly indicate that the structure of the primosome assembly site under analysis consists of two hairpins which interact with each other. When the sites of pancreatic DNase attack are plotted on the proposed double hairpin structure, the 5' cleavage sites all map to one duplex while the 3' sites map to the other. The observation that, under factor Y ATPase activating conditions, the 3' hairpin is largely refractory to the action of pancreatic DNase indicates that tertiary interactions between the two duplexes render a portion of the DNA structure inaccessible to the nuclease. PMID- 2931434 TI - Primary structure of single-chain pro-urokinase. AB - Single-chain pro-urokinase is an inactive proenzyme form of human urokinase with a single-chain structure and a Mr of 50,000 and converted to the active two-chain form by catalytic amounts of plasmin. It was isolated from culture fluid of human kidney cells and subjected to chemical (CNBr) and proteolytic (lysyl endopeptidase) degradation. The resulting peptides were separated by reverse phase high performance liquid chromatography and subjected to automated sequence analysis. Amino acid sequence of 85% of the 411 residues recovered in 17 peptides were found to be consistent with those of the A chain (157 amino acids) and B chain (253 amino acids) of human urokinase reported by Gunzler and co-workers (Gunzler, W. A., Steffens, G.J., Otting, F., Kim, S.-M., A., Frankus, E., and Flohe, L. (1982) Hoppe-Seyler's Z. Physiol. Chem. 363, 133-141; 1155-1165; Steffens, G.J., Gunzler, W.A., Otting, F., Frankus, E., and Flohe, L. (1982) Hoppe-Seyler's Z. Physiol. Chem. 363, 1043-1058). It revealed the presence of Lys at position 158 in single-chain pro-urokinase through which the two polypeptide chains of human urokinase are unified into one molecule. In addition, firm evidence was found that upon activation by plasmin single-chain pro-urokinase is cleaved at the Lys-Ile bond between residues 158 and 159, resulting in the formation of a two-chain urokinase molecule held together by one disulfide linkage. These results indicate that the cleavage at the Lys-Ile bond between residues 158 and 159 is responsible for conformational change, appearance of enzyme activity and reduction of its high affinity for fibrin. PMID- 2931435 TI - Labeling of Chlamydomonas 18 S dynein polypeptides by 8-azidoadenosine 5' triphosphate, a photoaffinity analog of ATP. AB - The 18 S dynein from the outer arm of Chlamydomonas flagella is composed of an alpha subunit containing an alpha heavy chain (Mr = approximately 340,000) and an Mr = 16,000 light chain, and a beta subunit containing a beta heavy chain (Mr = approximately 340,000), two intermediate chains (Mr = 78,000 and 69,000), and seven light chains (Mr = 8,000-20,000). Both subunits contain ATPase activity. We have used 8-azidoadenosine 5'-triphosphate (8-N3 ATP), a photoaffinity analog of ATP, to investigate the ATP-binding sites of intact 18 S dynein. 8-N3ATP is a competitive inhibitor of 18 S dynein's ATPase activity and is itself hydrolyzed by 18 S dynein; moreover, 18 S dynein's hydrolysis of ATP and 8-N3ATP is inhibited by vanadate to the same extent. 8-N3ATP therefore appears to interact with at least one of 18 S dynein's ATP hydrolytic sites in the same way as does ATP. When [alpha- or gamma-32P]8-N3ATP is incubated with 18 S dynein in the presence of UV irradiation, label is incorporated primarily into the alpha, beta, and Mr = 78,000 chains; a much smaller amount is incorporated into the Mr = 69,000 chain. The light chains are not labeled. The incorporation is UV dependent, ATP-sensitive, and blocked by preincubation of the enzyme with vanadate plus low concentrations of ATP or ADP. These results suggest that the alpha heavy chain contains the site of ATP binding and hydrolysis in the alpha subunit. In the beta subunit, the beta heavy chain and one or both intermediate chains may contain ATP-binding sites. PMID- 2931436 TI - Tibio-talar slant in Down syndrome. AB - The presence of tibio-talar slant is reported in an adult patient with Down syndrome. No previous description of this deformity in connection with Down syndrome has been found. PMID- 2931437 TI - Organic anions stabilize the reactivated motility of sperm flagella and the latency of dynein 1 ATPase activity. AB - Substitution of any of a variety of organic anions, including acetate, propionate, lactate, gluconate, and succinate, for chloride in the reactivation medium improves the motility of demembranated sperm of Tripneustes gratilla. At the optimum concentration of 0.20 N, all of these anions improve the duration of motility, with lactate and gluconate being the best. The Michaelis constant for beat frequency (Kmf) is lower (0.11-0.14 mM at 22 degrees C) in most of the organic anions than it is in Cl- (0.20 mM), and the minimum ATP concentration required to support oscillatory beating is reduced from 10 microM in chloride to 2 microM in acetate, which together indicate a greater affinity of the axonemal ATPase for MgATP2- in the organic anions media. The maximal beat frequency, fmax, is as high as 42 Hz in 0.2 N succinate compared to 31 Hz in Cl-, whereas the mean bend angle averages 2.8 rad in acetate compared to 2.4 rad in Cl-; these values give a calculated average velocity of tubule sliding of approximately 15 micron/s in acetate and succinate, which is approximately 30% greater than the value of 11 micron/s observed in chloride. The reactivated sperm are sixfold more sensitive to vanadate inhibition in 0.2 M acetate than they are in 0.15 M Cl-. The specific ATPase activity of soluble dynein 1, which increases more than 15-fold between 0 and 1.0 N Cl-, undergoes only a twofold activation over the same range of organic anion concentration, and, like the reactivated motility, is up to 50-fold more sensitive to vanadate. This greater apparent mechanochemical efficiency and the increased sensitivity to vanadate inhibition in the organic anions suggest that they, unlike chloride, do not promote the spontaneous dissociation of ADP and PO4(3-) from the dynein-ADP-PO4 kinetic intermediate in the dynein crossbridge cycle. The use of organic anion media may lead to significant improvements in reactivation of other motile and transport systems. PMID- 2931438 TI - Mechanisms of cytoskeletal regulation: modulation of membrane affinity in avian brush border and erythrocyte spectrins. AB - The spectrins isolated from chicken erythrocytes and chicken intestinal brush border, TW260/240, share a common alpha subunit and a tissue-specific beta subunit. The ability of these related proteins to bind human erythrocyte inside out vesicles (IOVs) and human erythrocyte ankyrin in vitro have been quantitatively compared with human erythrocyte spectrin. Chicken erythrocyte spectrin binds human IOVs and human ankyrin with affinities nearly identical to that for human erythrocyte spectrin. TW260/240 does not significantly bind to either IOVs or ankyrin. These results demonstrate a remarkable tissue preservation of ankyrin-binding capacity, even between diverse species, and confirm the role of the avian beta-spectrins in modulating this functionality. Avian brush border spectrin may represent a unique spectrin which serves primarily as a filament cross-linker and which does not interact strongly with membrane-associated proteins. PMID- 2931440 TI - Binding and phagocytosis of fibronectin-coated beads by BHK cells: receptor specificity and dynamics. AB - Studies on the receptor specificity and dynamics involved in fibroblast phagocytosis of latex beads revealed the following: 1) Ligands other than fibronectin such as concanavalin A (ConA) and serum spreading factor, when coated on latex beads, were found to promote phagocytosis of the beads. This indicates that fibroblast phagocytosis, like spreading, is a ligand-receptor mediated phenomenon not specifically requiring fibronectin (pFN); 2) Anti-pFN antibodies were found to inhibit the ability of cells to ingest pFN-coated beads that previously were bound on the cell surfaces. Consequently, binding of beads to the cell surfaces per se is not a sufficient signal to promote ingestion of the beads; 3) Finally, divalent cations protected receptor function necessary for phagocytosis of pFN-coated beads from proteolysis by trypsin, as previously was found for receptors involved in cell attachment and spreading on pFN-coated culture dishes. Recovery experiments carried out with cells whose surface receptors had been destroyed indicated that there was an internal (or cryptic cell surface) pool of receptors that amounted to at least 50% of the receptors normally found on the cell surface. After complete destruction of the cell surface and cryptic pools of receptors, reappearance of receptors required for bead binding and phagocytosis required several hours and did not occur in the absence of new protein synthesis. PMID- 2931439 TI - The substructure of isolated and in situ outer dynein arms of sea urchin sperm flagella. AB - Outer-arm dynein from the sperm of the sea urchin S. purpuratus was adsorbed to mica flakes and visualized by the quick-freeze, deep-etch technique. Replicas reveal particles comprised of two globular heads joined by two irregularly shaped stems which make contact along their length. One head is pear-shaped (18.5 X 12.5 nm) and the other is spherical (14.5-nm diam). The stems are decorated by a complex of bead-like subunits. The same two-headed protein is found in the 21S dynein-1 fraction of sucrose gradients. The beta-heavy chain/intermediate chain 1 (beta/IC-1) dynein subfraction, produced by low-salt dialysis and zonal centrifugation of the high-salt-extracted dynein-1, contains only single-headed molecules with single stems. These heads are predominantly pear-shaped (18.5 X 12.5 nm). Since 21S dynein-1 contains two heavy chains (alpha and beta), and the beta/IC-1 subfraction is comprised of only the beta-heavy chain (Tang et al., 1982, J. Biol. Chem. 257: 508-515), we conclude that each head is formed by a heavy chain, that the pear-shaped head contains the beta-heavy chain, and that the spherical head contains the alpha-heavy chain. The in situ outer dynein arms of demembranated sperm were also studied by the quick-freeze, deep-etch method. When frozen in reactivation buffer devoid of ATP, each arm consists of a large globular head that attaches to the A-microtubule by distally skewed subunits and attaches to the B-microtubule by a slender stalk. In ATP, this head shifts its orientation such that it can be seen to be constructed from two globular domains. We offer possible correlates between the in situ and the in vitro images, and we compare the structure of sea-urchin dynein with dynein previously described from Chlamydomonas and Tetrahymena. PMID- 2931441 TI - Insulin receptor capping and its correlation with calmodulin-dependent myosin light chain kinase. AB - Both fluorescence microscopy and fluorometric analysis techniques have been used to characterize insulin receptor capping in IM-9 human lymphoblastoid cells. Morphologically, insulin caps appear similar to lectin or antiimmunoglobulin induced caps displaying a preferential accumulation of actin, myosin, and actin binding protein directly underneath the cap structure. Using the fluorescent calcium indicator quin2 we have detected no change in the calcium activity following insulin stimulation. However, in the presence of a number of calmodulin inhibitors, such as W-5, W-7, W-12, and trifluoperazine (TFP), insulin capping is significantly inhibited, which implies that a calmodulin-regulated process is involved. Using double immunofluorescence microscopy, we have found that the calmodulin-dependent myosin light chain kinase (MLCK) is concentrated directly beneath insulin caps. Upon treatment with trifluoperazine (TFP), the redistribution of both MLCK and insulin receptors are inhibited concomitantly. Our data indicate that the calmodulin-dependent myosin light chain kinase may be directly responsible for the activation of actomyosin-mediated contractility during insulin receptor capping. PMID- 2931442 TI - Ecto-nucleotide triphosphatase activity of human lymphocytes: studies of normal and CLL lymphocytes. AB - We have studied the apparent kinetic parameters of the ecto-nucleotide triphosphatase from CLL B lymphocytes and compared them to blood and tonsillar B and T cells. The Vmax of the ecto-ATPase activity in CLL B lymphocytes, was 65 +/ 10 fmol Pi/cell per 30 min compared to 37 +/- 2.1 in blood B lymphocytes, and 8.5 +/- 1.7 in blood T lymphocytes. The ATPase of membranes prepared from CLL, tonsillar B and T, and blood T lymphocytes had a relationship among the cell types similar to that seen in intact cells. However, no difference in the km for ATP, .17 mM, or the km for magnesium, .15 mM was found in the ecto-ATPase of CLL lymphocytes as compared to blood or tonsillar B cells. The ectoenzyme of CLL cells hydrolyzed GTP, ITP, CTP, and UTP as well as ATP. Further, ATP added to an enzyme assay containing an alternative nucleotide did not result in increased phosphate release. Nucleotide acceptance of blood B and T lymphocytes was very similar to that of CLL B cells. ATP inhibited phosphate release when present in excess of magnesium in both CLL and blood B lymphocytes. These data indicate that there is greater ectonucleotide triphosphatase activity in tonsillar and blood B lymphocytes, including CLL, as compared either to blood or tonsillar T lymphocytes. However, CLL cells showed no qualitative difference from blood or tonsillar B cells in ectonucleotidase activity. Thus, the higher activity in CLL cells is "B cell-like" and might reflect, also, their maturation stage or monoclonal origin. PMID- 2931443 TI - A self-renewing, bipotential erythroid/mast cell progenitor in continuous cultures of normal murine bone marrow. AB - We have established permanent lines of nonadherent cells from fresh normal mouse bone marrow in media containing pokeweed mitogen-stimulated spleen cell conditioned medium (PWSCM). These lines continuously produced erythropoietic progenitor cells (detected by their ability to form erythroid bursts in semi solid medium containing erythropoietin) together with cells having characteristics of the mast cell lineage (as demonstrated by metachromatic staining with toluidine blue, histamine content and membrane receptors for IgE). Sixteen such cell lines have been established in sixteen attempts. Cloning experiments were carried out to determine the nature of the progenitor cell(s) responsible for the permanence of these cultures. When cells were cultured in methylcellulose medium containing PWSCM, colonies were observed which reached macroscopic size after 4 weeks of incubation. Replating of individual primary colonies resulted in secondary colony formation, indicating the presence of progenitor cells with self-renewal potential. Forty-seven primary colonies were picked and their cells were suspended in liquid culture medium containing PWSCM. Of these, twenty-one could be expanded to establish permanently growing sublines. Sixteen of these sublines were found to be composed of both erythroid progenitors and mast cells. In five sublines only mast cells could be seen; none of the sublines appeared to be purely erythroid. Karyotypic analysis of mast cells and of erythroid cells of seven sublines derived from individual colonies which arose in cocultures of male and female cells revealed that the mast cells and erythroid cells were both of the same sex in each of the seven sublines; this demonstrates the single cell origin of each colony and of the two lineages derived from it. We conclude that these nonadherent, factor-dependent cell lines are maintained by self-renewal and differentiation of bipotential progenitor cells apparently restricted to the erythroid and mast cell lineages. PMID- 2931444 TI - [Parietal metastasis after fine needle cytopuncture of a duodenal adenocarcinoma]. PMID- 2931445 TI - L-Thyroxine-induced leukopenia in a patient with Hashimoto's disease: involvement of suppressor-cytotoxic T cells. AB - A study of in vitro reactivity to L-T4, as assessed by peripheral blood lymphocyte transformation, was carried out in a patient with Hashimoto's disease who developed leukopenia during treatment with L-T4. L-T4 stimulated lymphocyte transformation in this patient. The proliferating cells were of T lineage and further typing demonstrated that they bore the OKT8 antigen. Cell-mediated immune reactions mediated by OKT8+T cells might have caused the leukopenia, although other mechanisms involving cytotoxic antibodies or antibody-dependent cell mediated cytotoxicity cannot be excluded. PMID- 2931447 TI - Alterations of functional subsets of T helper and T suppressor cell populations in acquired immunodeficiency syndrome (AIDS) and chronic unexplained lymphadenopathy. AB - We have studied the distribution of Leu8 and Ia on T cells of the helper (T4) and suppressor (T8) phenotype in homosexual men with chronic unexplained lymphadenopathy, homosexual men with the acquired immunodeficiency syndrome (AIDS), and homosexual and heterosexual controls. Decreased numbers of helper T cells in lymphadenopathy patients are due to a decrease in the T4:Leu8+ subset, whereas in AIDS patients, both the T4:Leu8+ and the T4:Leu8- subsets were decreased. PMID- 2931446 TI - Studies on natural, antibody-dependent, and interleukin-2-activated killer-cell activity of a patient with mucolipidosis III as a test of the mannose-6-phosphate lytic acceptor hypothesis. AB - The natural (NK), antibody-dependent (K), and interleukin-2-generated (LAK) killer-cell activity of a patient with mucolipidosis III (ML III; an autosomal recessive defect in UDP-N-acetylglucosamine: lysosomal enzyme N-acetylglucosamine 1-phosphotransferase) was studied to determine whether or not the defect in the phosphorylation of lysosomal enzyme mannose residues resulted in a failure of target-cell lysis, as would be predicted from recent studies showing NK inhibition by phosphorylated sugars, especially mannose-6-phosphate. The patient was studied in parallel with normal donors known to be at the high and low extremes of NK activity. The following results were obtained: NK activity was markedly elevated against K562, Molt-4, human fibroblasts, HL-60, and MeWo to levels approximately one to two times that of our previous highest donor and five times the mean of normal donors previously tested. Interleukin-2-generated killer cell activity and antibody-dependent cell-mediated cytotoxicity against antibody coated P815 cells were normal and increased, respectively. HNK-1-positive cells were normal in frequency (7.3 +/- 1.7%), while lytic conjugates were proportional to activity (3.9 +/- 0.6 vs 2.7 +/- 0.4% for the "high" donor), and this was attributable to an increased proportion of lytic cells. The addition of fresh serum from the ML III patient had no effect on the NK activity of normal donors and the effects of preincubation with interferon (enhancement), monensin (inhibition), fructose-6-phosphate (inhibition), and mannose-6-phosphate (inhibition) were identical to those seen using lymphocytes from normal donors. Studies on the NK activity of the parents and two normal female siblings showed that the father's NK activity was high, the mother's was low, and both siblings' was intermediate but low. The data obtained suggest that the inability of lymphocytes to phosphorylate lysosomal enzyme mannose residues had no effect on NK-, K-, or LAK-cell function and that the mechanism of target-cell lysis is independent of either a mannose-6-phosphate-bearing lytic moiety or a mannose-6 phosphate-dependent ligand mechanism. PMID- 2931449 TI - Decreased autologous mixed lymphocyte reaction in multiple sclerosis. AB - The autologous mixed lymphocyte reaction (AMLR) measures the T-cell response to antigens on the surface of autologous non-T-cells. Studies have shown a decreased ability of T-cells to proliferate during the AMLR in a number of autoimmune and viral disorders. The AMLR was studied in 56 patients with multiple sclerosis (MS), a presumed autoimmune disease of the central nervous system, and the response was correlated with T-cell subsets. The AMLR was decreased in active MS patients (3 117 +/- 573 cpm) as compared to inactive patients (5 896 +/- 1 800 cpm) (P less than 0.05) and normal controls (7 782 +/- 1 725 cpm) (P less than 0.01). There was no significant difference between inactive patients and normal controls (P greater than 0.1). A more pronounced difference was also seen when patients with active disease associated with peripheral blood T4/T8 ratios greater than 3.0 (1 045 +/- 223 cpm) were compared with normal controls (P less than 0.01). In addition, MS patients with T4/T8 ratios of less than 1.0 had an increased AMLR (9 256 +/- 1 762 cmp) as compared to patients with either a high T4/T8 ratio (P less than 0.001) or normal ratio (P less than 0.05). Thus, multiple sclerosis patients with clinically active disease have a decreased AMLR which correlates with high T4/T8 ratios in a subgroup of patients. PMID- 2931448 TI - Craniofacial and mucopolysaccharide abnormalities in Kniest dysplasia. AB - Serial roentgencephalograms of a male patient with Kniest dysplasia were obtained between 1 7/12 and 11 3/12 years of age and were analyzed and compared to cephalometric normative data. The patient displayed macrocephaly with increased size of the neurocranium in all three dimensions. The cranial base angle was significantly flattened, partly as a result of anterior displacement of the sella turcica. The odontoid process was short and wide. At 11 years of age there was bony fusion between the anterior arch of the atlas and the odontoid process as well as between the posterior arch of the atlas and the cranial base. The facial skeleton, including the nasal bones, infra-orbital rims, maxilla and mandible, was retropositioned relative to the anterior cranial base. The mandibular retrognathia was pronounced at an early age but improved with growth. At age 11 years the patient had a straight facial skeletal profile. Examination of the patient's 24-hour urinary excretion of keratan sulfate revealed values markedly elevated for his age. Three additional patients with Kniest dysplasia demonstrated similarly increased excretion of this glycosaminoglycan. The diagnosis of Kniest dysplasia can usually be made from roentgenograms of the extremities, the spine, and the pelvis. However, the morphologic characteristics of the head, as shown by cephalometric analysis, and the increased urinary excretion of keratan sulfate add confirmatory evidence useful in differential diagnosis. PMID- 2931450 TI - Fracture of the lumbar vertebral apophysis. AB - Three cases of vertebral apophyseal fracture and displacement presenting with back pain are reported. Literature review revealed 11 other such cases, and these are compared. Computed tomography scan was found to be an excellent tool to confirm this diagnosis. PMID- 2931451 TI - Inhibitory effect of a human T cell hybrid factor on both cell growth and mixed lymphocyte reactivity. Correlation with class II molecule expression. AB - We recently reported the biological activity and some of the biochemical characteristics of a factor produced by a human T cell hybrid clone able to block hematopoietic progenitor cell proliferation. This 85-kD protein factor, which we have termed colony-inhibiting lymphokine (CIL), has growth regulatory activity on bone marrow precursors bearing Ia (class II) antigens of either granulocytic monocytic (CFU-GM) or erythroid lineage (BFU-E and CFU-E). Experiments aimed to investigate the specificity of the inhibitory effect on hematopoietic progenitor cell growth suggested that the expression of HLA-DR surface antigens was required on the target cells. We describe in this communication how DR+ cell lines ceased dividing after a few days of culture in the presence of CIL, whereas DR- cell lines were completely unaffected. The increased DR expression on the ML3 cell surface, mediated by the activity of the gamma interferon (IFN gamma), increases the sensitivity to the growth inhibition factor of the ML3 cell line. To verify the hypothesis that the DR antigens might serve as receptors for the factor, enabling it also to interfere in the immune response, we tested CIL in a mixed lymphocyte reaction (MLR), one of the best known in vitro Ia antigen-dependent T cell-mediated immune responses. CIL is able to block major histocompatibility complex-allogeneic MLR both in human and mouse systems. The data indicate that CIL recognizes a nonpolymorphic structure (presumably on all Ia molecules) presented by stimulator cells of either species, and thereby interferes with specific interactions between stimulator and responder cells. Blocking of the alloantigen stimulation stage is also indicated, since CIL is effective only if added to the culture medium during the first 48 h of the MLR. Finally, mouse monoclonal anti-DR antibodies are able to sharply reduce CIL activity on sensitive DR+ cell lines. CIL may act physiologically as a multifunctional mediator in a complex network that links regulation of bone marrow differentiation and the generation of immune responses. PMID- 2931452 TI - Identification of malignant plasma cell precursors in the bone marrow of multiple myeloma. AB - Precursors of plasma cells were studied in the bone marrow of 28 patients with multiple myeloma, plasma cell leukemia, and benign monoclonal gammopathy. Pre-B and B cell populations were analyzed with anti-B monoclonal antibodies corresponding to the clusters standardized at the Leucocyte Typing Workshops in Paris and Boston (CD9, CD10, CD19-22, CD24). In advanced forms of plasma cell malignancies, such as cases of multiple myeloma in stages II and III and of plasma cell leukemia, some cells of lymphoid morphology expressed common acute lymphoblastic leukemia antigen (CALLA, CD10) and HLA-DR, but contained no detectable terminal deoxynucleotidyl transferase enzyme. These CALLA+ cells were absent in benign monoclonal gammopathies. In multiple myeloma, the CALLA+ cells were negative for surface and cytoplasmic immunoglobulins (Ig), and, unlike CALLA+, terminal deoxynucleotidyl transferase (TdT+) pre-B cells in the normal bone marrow also failed to react with antibodies to B cell-associated antigens such as CD9, CD19, CD22, and CD24. The CALLA+, Ig- cells could be regarded as preplasmacytic since, after having been separated and stimulated with the phorbol ester 12-0-tetradecanoyl-phorbol-13 acetate in vitro, they transformed into plasma cells and synthesized the same heavy and light chains as myeloma cells. PMID- 2931454 TI - Expression of the common acute lymphoblastic leukaemia antigen (CALLA gp100) in the brush border of normal jejunum and jejunum of patients with coeliac disease. AB - Expression of the gp100 common acute lymphoblastic leukaemia antigen (CALLA) was studied in the mucosa of the gut by means of indirect immunofluorescence on cryostat tissue sections with a panel of eight monoclonal antibodies to common acute lymphoblastic leukaemia antigen (anti-CALLA antibodies) and two antibodies to non-CALLA leukaemic antigens. Expression of CALLA was absent from normal stomach epithelium, adult and fetal colonic epithelium of normal histology, and colonic epithelium from patients with Crohn's disease or ulcerative colitis. By contrast, all eight anti-CALLA antibodies gave a characteristic reaction in normal adult and fetal small bowel mucosa, with specific localisation to the entire brush border of jejunal epithelium. Whereas seven of these antibodies reacted both with normal jejunal epithelium and with the damaged epithelium of patients with coeliac disease, antibody RFAL-2 reacted strongly only with histologically normal small bowel but more weakly in patients with coeliac disease to a degree related to the amount of histological abnormality. Expression of the moeity like CALLA identified with RFAL-2 was strongest in crypt epithelium and proportionally diminished along the villi according to the amount of histological damage in coeliac disease, being essentially absent in patients with "subtotal villous atrophy." PMID- 2931453 TI - Acquired Bernard-Soulier syndrome. Evidence for the role of a 210,000-molecular weight protein in the interaction of platelets with von Willebrand factor. AB - A patient with a lymphoproliferative disorder developed bleeding associated with a prolonged bleeding time and a selective defect of platelet aggregation in response to ristocetin. The patient's purified IgG was shown to inhibit aggregation of washed normal platelets by ristocetin and von Willebrand factor (F VIII:vWF). By Western blotting, it was shown that antibody bound specifically to an antigen of Mr 210,000 present on normal platelets but missing on platelets from patients with congenital Bernard-Soulier syndrome (BSS). Binding was effected by the F(ab)2 portion of the IgG, indicating the presence of an autoantibody rather than an immune complex. These results suggest that the 210,000-Mr protein is involved in the interaction of F VIII:vWF with platelets. Furthermore, we have demonstrated the apparent absence of an additional protein on congenital BSS platelets. Heat-aggregated IgG was also shown to bind to the 210,000-Mr protein, suggesting that this protein may function as an Fc receptor on platelets. The relationship of the 210,000-Mr protein to glycoprotein Ib and the precise role of this protein in the interaction of platelets with F VIII:vWF need to be characterized. PMID- 2931455 TI - Cutaneous drug reactions: pathogenesis and clinical classification. AB - Cutaneous drug reactions may be classified with respect to pathogenesis and clinical morphology. They may be mediated by immunologic and nonimmunologic mechanisms. Immunologic reactions require host immune response and may result from IgE-dependent, immune complex-initiated, cytotoxic, or cellular immune mechanisms. Nonimmunologic reactions may result from nonimmunologic activation of effector pathways, overdosage, cumulative toxicity, side effects, ecologic disturbance, interactions between drugs, metabolic alterations, or exacerbation of preexisting dermatologic conditions. Certain defined, cutaneous, morphologic patterns are frequently associated with cutaneous drug reactions. These include urticaria, photosensitivity eruptions, erythema multiforme, disturbance of pigmentation, morbilliform reactions, fixed drug reactions, erythema nodosum, toxic epidermal necrolysis, lichenoid eruptions, and bullous reactions. In addition, certain drugs cause defined cutaneous syndromes. These include iodides and bromides, hydantoins, corticosteroids, antimalarial agents, gold, cancer chemotherapeutic agents, tetracyclines, thiazides and sulfonamides, nonsteroidal anti-inflammatory agents, and coumarin. The criteria for evaluation of possible drug reactions are presented and reviewed. PMID- 2931456 TI - An outbreak of contact dermatitis in farm workers. AB - Fourteen of twenty-six migrant workers developed contact dermatitis at a single tomato-strawberry farm in Tennessee. Investigation identified one of eleven pesticides used by the farmer, 2,4-dichloro-6-(o-chloroanilino)-s-triazine anilazine; Dyrene), as the cause of the dermatitis in six of seven workers who were available for patch testing. As a result of this investigation, the label on Dyrene has been revised to warn users of possible sensitization. PMID- 2931457 TI - Delayed hypersensitivity to scopolamine delivered by a transdermal device. AB - Transdermal devices are now marketed for the delivery of systemic medications through the skin. This report confirms delayed hypersensitivity to scopolamine, the active ingredient in Transderm-Scop. Patch testing with structurally related alkaloids suggests the active antigenic site on the scopolamine molecule. The mechanism of drug delivery by the transdermal device is discussed, along with the features that make this an attractive method of drug administration. Dermatologists should be familiar with these devices, since broader future applications can be expected. PMID- 2931458 TI - Tetracycline-induced fixed drug eruptions: influence of dose and structure of tetracyclines. PMID- 2931459 TI - Erythroderma secondary to esophageal carcinoma. PMID- 2931460 TI - Update on pedodontics in a period of improving dental economics. AB - The dental services sector of the economy is a growth industry; however, many changes have occurred since the 1979-1980 recession. The population under the age of eighteen has continued to decrease, and the number of pedodontists has increased. Major changes are occurring in the incidence and prevalence of dental diseases. PMID- 2931461 TI - Pedodontists' attitudes toward parental presence during children's dental visits. AB - The purpose of this survey of Connecticut pedodontists was to determine the prevailing attitudes and practices of pedodontists concerning parents presence during examination and treatment visits. Response percentage was high, prompt, and strikingly bimodal, suggesting both a high degree of interest in, and strong views on, the topic as it pertains to patient management. PMID- 2931462 TI - The need for general anesthesia for the dental treatment of mentally handicapped patients: a follow-up study. AB - Over a period of years, it appeared possible to provide routine treatment without the use of general anesthesia for nearly all of the patients. The majority required treatment under general anesthesia because of their lack of previous dental care. PMID- 2931464 TI - Complications of dermabrasion resulting from excessively cold skin refrigeration. AB - Three patients developed complications following dermabrasion with a new potent skin refrigerant mixture. Freezing can usually be performed more rapidly with such mixtures, but the risk of complications may be greater. PMID- 2931463 TI - Basal cell carcinomas arising in seborrheic keratoses. PMID- 2931465 TI - Acquired immune deficiency syndrome (AIDS): disease characteristics and oral manifestations. AB - This article has reviewed the disease process and oral manifestations of AIDS. Specifically, dentists should review the medical history and perform an overall health assessment for all dental patients before treatment is rendered. Attention should be directed to the prodromal signs and symptoms of AIDS. If dental treatment of a patient with AIDS is required, strict infection control guidelines are mandatory. PMID- 2931466 TI - Orthodontic care for medically compromised patients: possibilities and limitations. AB - Medically compromised children and adults are increasingly likely to seek orthodontic care as improved medical management creates more long-term survivors. For the majority, treatment of orthodontic problems is feasible, but special precautions usually are required. These include medical consultation to establish the patient's prognosis, maintaining a current knowledge of drug therapy, and modifications in office procedures. Patients with a history of multiple transfusions should be presumed to be hepatitis carriers until proved not to be, and special precautions to protect office staff members and other patients should be taken. Decreased resistance to infection is a common complicating factor in medically compromised patients. Dentists must therefore avoid mucosal irritation and carefully monitor periodontal health. The practitioner should be alert to side effects of drug treatment such as xerostomia and depressed immune response, and be aware of the particular features of the underlying disease. Bleeding disorders, which can be managed by replacement of missing clotting factors, do not contraindicate orthognathic surgery. The major contraindication is poor anesthetic risk, which almost always is true for patients having sickle cell anemia because of poor blood oxygen saturation. Because orthodontic treatment can provide positive benefits, it should not be withheld solely because of the presence of a serious medical problem. With appropriate management, successful orthodontic treatment can be done for most patients. PMID- 2931467 TI - Alzheimer's disease: an emerging affliction of the aging population. AB - Alzheimer's disease is one of several brain disorders under the broad category of dementia. It is a gradually debilitating illness with no known cure. The first symptom is usually a slowly increasing memory loss, beginning between 40 and 65 years of age. As the disease progresses, the brain begins to deteriorate more rapidly, until it literally stops functioning. Of great concern is the projection that the number of people who will have Alzheimer's disease will double by the year 2030 because of the rising elderly population. Treating this population will escalate from the current estimate in excess of $2.5 billion to more than $6 billion. Speculation toward the increasing costs in money and workforce has led to an accelerated program in search of a cure or at least a symptomatic therapy for this condition. One of the most promising research leads is the striking connection between Alzheimer's disease and Down's syndrome and certain cancers: - Virtually 100% of patients with Down's syndrome who survive past age 35 show the same mental deterioration and identical brain changes seen in patients with Alzheimer's disease, including the presence of plaque and neurofibrillary tangles.--The presence of a high percentage of Down's syndrome among relatives of patients with Alzheimer's disease. --A high incidence of certain types of syndrome and among relatives of people who have Alzheimer's disease, such as leukemia, lymphomas, Hodgkin's disease, and immune system disorders. The key to the intercorrections between Alzheimer's disease and Down's syndrome seems to be a genetic component related to chromosome 21.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2931468 TI - Left ventricular mass and volume/mass ratio determined by two-dimensional echocardiography in normal adults. AB - This study prospectively defined the range of left ventricular mass and volume/mass ratio determined by two-dimensional echocardiography in 84 normal adults. A modified Simpson's rule algorithm was used to calculate ventricular volumes from orthogonal two and four chamber apical views. An algorithm based on a model of the left ventricle as a truncated ellipsoid was used to calculate ventricular mass. Like left ventricular volumes, left ventricular mass values were larger in normal men than in women (mean 148 versus 108 g, p less than 0.001) and remained larger after correction for body surface area. Volume/mass ratios, however, were constant at end-diastole (0.80) and end-systole (0.26). The influence of age and heart rate on all variables in this normal group was minimal, and no correction for these variables was necessary. The definition of normal mass, volume and volume/mass ratios by two-dimensional echocardiography will facilitate the noninvasive, quantitative diagnosis of left ventricular hypertrophy and help clarify the relation between hypertrophy and systolic wall stress. PMID- 2931469 TI - Laser recanalization of acutely thrombosed coronary arteries in live dogs: early results. AB - Laser recanalization was attempted in thrombosed coronary arteries of 10 dogs. In all dogs a coronary thrombus was obtained by passing a low grade electrical current through a guide wire advanced into the artery. Recanalization was then attempted using an argon laser with energy levels ranging from 3 to 30 J. In six dogs a 140 micron core optical fiber was positioned proximal to the thrombus and lasing was done during fiber advancement. The thrombosed artery was recanalized in one dog, perforated in four and neither recanalized nor perforated in one. In the remaining four dogs a steerable guide wire was advanced across the thrombus and a catheter was passed over the guide wire and exchanged for a 200 micron core optical fiber. After fiber withdrawal, mechanical recanalization without lasing was performed in one of the four dogs. In the remaining three dogs, both the fiber and the catheter were again advanced distal to the thrombus and lasing was done during withdrawal; this caused coronary perforation in all dogs. Laser recanalization of thrombosed coronary arteries in dogs using currently available techniques is feasible but results in a very high incidence of perforation. PMID- 2931470 TI - Anatomy of the crista supraventricularis: its importance for understanding right ventricular function, right ventricular infarction and related conditions. AB - During careful studies of the human cardiac conduction system the anatomy of the crista supraventricularis is an inescapable concomitant demonstration. For the purpose of this report the observations from about 1,000 human hearts were combined with special additional studies of 75 human hearts (50 adults, 25 infants), 30 dogs and 5 chickens. The crista supraventricularis is similar in human and canine hearts. Avian hearts differ from mammal hearts in that they contain only a muscular right atrioventricular valve which replaces the crista supraventricularis. In addition to dividing the inflow and outflow pathways of the right ventricle, the crista supraventricularis is crucially located to join the interventricular septum and left ventricle to much of the right ventricular free wall, thereby playing an important role in emptying the right ventricle and closing the tricuspid valve. On the basis of these observations, the function of the crista supraventricularis is examined relative to right ventricular systole, right ventricular infarction, various electrophysiologic problems, the performance of cardiac surgery and new questions in cardiac imaging. PMID- 2931471 TI - The disease-free wall in coronary atherosclerosis: its relation to degree of obstruction. AB - Coronary atherosclerotic lesions are more often located eccentrically (70%) than concentrically (30%). In this study, the configuration of eccentric coronary artery atherosclerotic lesions was assessed by means of computerized planimetry in 100 specimens of eccentric arterial lesions. Special attention was given to the relation between the disease-free wall and the severity of obstruction. The mean disease-free wall are length measured between 17 and 23% of the total vessel circumference in eccentric coronary artery lesions that obstructed 50 to 90% of the cross-sectional area. This ratio persisted irrespective of the location of the lesion within the vessel and was not significantly different with vessels of different sizes. The presence of disease-free arcs of coronary artery wall as observed in this pathologic study may relate to three factors in clinical coronary artery disease: The published observations of spasm in segments of arteries harboring structural obstructive lesions may be explained by the frequent presence of uninvolved arcs of coronary artery walls. Multiple views during coronary arteriography are necessary to accurately reflect the degree of obstruction. The results of percutaneous transluminal coronary angioplasty may be influenced by both the disease-free arc and the atheromatous obstruction. PMID- 2931472 TI - Coronary luminal shape and the arc of disease-free wall: morphologic observations and clinical relevance. PMID- 2931474 TI - Percutaneous transluminal coronary angioplasty. PMID- 2931473 TI - Immediate and short-term benefit of multilesion coronary angioplasty: influence of degree of revascularization. AB - The safety and short-term therapeutic benefit of multilesion percutaneous transluminal coronary angioplasty was assessed in 135 patients, 66 of whom had a minimum of 6 months of follow-up study. Primary success, defined as successful dilation of the most critical lesion or all lesions attempted without major in hospital complications was obtained in 117 (87%) of the 135 patients. Cardiac complications associated with the procedure were uncommon; prolonged angina occurred in 5% and myocardial infarction in 3%; emergency coronary bypass surgery was performed in 4% of the patients. There were no deaths. Complete revascularization was achieved in 46% of the 117 patients with a primary success. Of the 66 patients eligible for 6 month follow-up, 80% had an uncomplicated course and required no further procedures. Clinical improvement by at least one angina functional class was observed in 90% of the patients. Cardiac events such as the need for a second revascularization procedure were significantly more common in patients who had incomplete versus complete revascularization (35 versus 9%; p = 0.018). Repeat coronary angiography performed an average of 5 months after angioplasty revealed restenosis in 18 of 22 symptomatic patients and 3 of 9 asymptomatic patients. Restenosis occurred at the site of a single dilation in 12 patients, at two sites in 8 patients and at three sites in 1 patient. Thus, multilesion coronary angioplasty is an important therapeutic option for selected patients with multivessel disease and can be performed with relatively low risk. Improvement in angina status can be expected even in patients who have incomplete revascularization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2931475 TI - Fiber number and type composition in extensor digitorum longus, soleus, and diaphragm muscles with aging in Fisher 344 rats. AB - Histochemical (M-ATPase) fiber typing was done on extensor digitorum longus, (EDL), soleus (SOL), and diaphragm (DIA) muscles of barrier-reared Fisher 344 rats obtained at four different ages (3, 9, 28, and 30 months) from the colonies of the National Institute of Aging. In the EDL there are no differences in the percent of type I fibers among the four age groups. The percent of type IIa and IIb fibers also showed no difference between the 3 and 30 month age groups. There was no apparent trend for an increase or decrease in the percent of type IIa or IIb fibers between the four age groups. In both the SOL and DIA muscles the percent of type I fibers was greater in the aged than in the young groups. The percent of type IIa fibers was lower in the 30 month group than in the younger groups for both muscles. The percent of type IIb (DIA) and IIc (SOL) fibers did not change between groups. Total fiber number per cross section of muscle showed no change in the EDL over this age range or in the SOL after 9 months of age. These findings bring into question published results that imply that decreasing fiber number and preferential loss of type II (a and b) fibers are typical aging phenomena. PMID- 2931476 TI - Class II histocompatibility antigen-mediated immunologic function of normal articular chondrocytes. AB - Using monoclonal antibodies, we examined the display of rabbit Ia by articular chondrocytes. We found that 29 to 46% of chondrocytes displayed Ia antigen compared with 46 to 60% of spleen cells. Ia antigen expression was not likely to be the result of enzyme treatment. To investigate antigen presenting activity of enzyme dissociated normal articular chondrocytes, adult rabbits were immunized in the front foot pads with ovalbumin (OVA) in complete Freund's adjuvant. Four to six weeks later, draining popliteal lymph node cells (LNC) were obtained. Articular chondrocytes were obtained by overnight collagenase, DNase, and hyaluronidase digestion of cartilage from both ends of femurs and proximal end of tibias. Antigen-presenting cells from spleen were used as positive controls. LNC and nylon wool-purified T cells were cultured with OVA pulsed and mitomycin C treated chondrocytes or spleen cells, and lymphocyte proliferation was measured by 3H-TdR uptake. Both chondrocytes and spleen cells showed antigen presenting activity, and stimulation of lymphocyte proliferation was inhibited by murine monoclonal anti-rabbit Ia antibody (2C4), whereas control plasmacytoma cell supernatants had no effect. When T cells were purified first by Sephadex G-10 and later by nylon wool columns, these cells were dependent on antigen-presenting cells for immunogen (OVA)-induced lymphocyte proliferation. Again, chondrocytes under these strict experimental conditions presented antigen to T cells. Chondrocytes also stimulated autologous and allogeneic normal lymphocytes. Thus, normal chondrocytes have Ia antigens on their surface and can function as antigen presenting cells. These results are significant for the understanding of local cellular interaction in the pathogenesis of rheumatoid arthritis. PMID- 2931477 TI - Mechanisms of suppressed cell-mediated immunity and impaired antigen-induced interleukin 2 production in granuloma-bearing mice. AB - Pulmonary granulomas were induced in BALB/c mice immunized with methylated bovine serum albumin in complete Freund's adjuvant by the intratracheal injection of plain agarose beads or beads conjugated to specific antigen. Large hypersensitivity granulomas developed around antigen-coupled beads in immunized animals. Smaller but still prominent granulomatous reactions developed around plain beads in immunized mice. In nonimmunized animals, both plain and antigen conjugated beads produced very small granulomas. Granuloma formation in sensitized animals was associated with suppressed delayed-type hypersensitivity reactions induced by the footpad injection of specific and nonspecific antigens. Lymph node cells from sensitized granuloma-bearing mice with cutaneous anergy showed suppressed specific and nonspecific antigen-induced proliferative responses in vitro. These cells also showed suppressed interleukin 2 production in response to specific antigen. Although no soluble suppressive factor was detected in granuloma extracts, suppressor cells were found in lymph nodes of granuloma-bearing mice, which could inhibit antigen-induced production of interleukin 2 by lymph node cells from immunized mice. Antigen-specific immunoglobulin G antibody production was not suppressed in immunized granuloma bearing mice. Previous studies from our laboratory have demonstrated migration inhibition factor and interleukin 1 activities in aqueous extracts prepared from granuloma-bearing lungs of immunized mice. These results and the findings reported here indicate that granuloma formation and the associated anergy observed in this system are primarily expressions of cell-mediated immunity; selective suppression of in vivo and in vitro expressions of cell-mediated immunity in granuloma-bearing mice may be due to impaired antigen-induced interleukin 2 production; and such impairment is caused by suppressor cells. PMID- 2931478 TI - Human peripheral blood lymphocytes from recently vaccinated individuals produce both type-specific and intertypic cross-reacting neutralizing antibody on in vitro stimulation with one type of poliovirus. AB - An in vitro system of poliovirus-specific antibody production by peripheral blood B cells on stimulation by the virus has been developed. Virus-neutralizing antibodies in culture supernatant fluids, or virus-specific antibody-secreting cells (ASC) were detected by microneutralization assay and ELISA-SPOT test, respectively. After booster immunization with polio vaccine, anti-poliovirus neutralizing ASC were present in circulation. This response was measurable between 5 and 12 days after booster vaccination. At between 12 and 90 days, another subset of B cells was found in peripheral blood that only produced poliovirus-specific neutralizing antibody after in vitro antigenic stimulation. The in vitro virus-induced response required B cells, monocytes, and T4+ (T helper) cells, and was shown to result from de novo protein synthesis. The anti poliovirus-neutralizing response in vitro could be dissected in a type-specific and intertypic cross-reactive response by using various antigen concentrations for in vitro stimulation. Evidence was obtained by absorption studies for the existence of intertypic cross-reactive neutralization-inducing epitopes. PMID- 2931479 TI - Murine leukemic cells inhibit IL 2 production by susceptible syngeneic splenocytes. AB - BALB/c mice fail to mount significant cell-mediated immunity against the syngeneic virally induced leukemia MCDV-12, and die approximately 10 days after tumor inoculation. Our studies in vitro demonstrated that BALB/c splenocyte and irradiated MCDV-12 cell co-culture led to reduced alloreactivity, including depressed interleukin 2 (IL 2) production. Tumor-induced immune suppression was genetically restricted, antigen nonspecific, and alleviated in part by exogenous IL 2 administration in vitro. Furthermore, mitogen stimulation of IL 2 production, not requiring self or alloantigen recognition, was unaffected by MCDV 12 exposure. These results indicate that tumor cells may escape from immunosurveillance by reducing IL 2 production in the immediate tumor vicinity, and suggest a potential role for major histocompatibility complex antigens in the immunosuppression mechanism. PMID- 2931480 TI - Regulation of IL 3 expression by glucocorticoids in cloned murine T lymphocytes. AB - We have examined the effects of glucocorticoids on the concanavalin A (Con A) stimulated production of interleukin 3 (IL 3) by a murine helper T cell clone Cl.Ly-1+2-/9. The addition of Con A to Cl.Ly-1+2-/9 cells leads to the rapid induction of both IL 3 mRNA and activity. A synthetic glucocorticoid, dexamethasone, inhibits the appearance of IL 3 activity in the supernatants of Con A-stimulated cells, as well as the accumulation of IL 3 mRNA in the cells. A similar effect is observed with other Con A-inducible mRNA, such as the mRNA encoding granulocyte-macrophage colony-stimulating factor (GM-CSF), but the hormone effects are not general; the constitutive synthesis of Thy-1 mRNA is not altered by dexamethasone treatment. Several lines of evidence suggest that dexamethasone directly inhibits transcription of the IL 3 gene: the kinetics of dexamethasone action on IL 3 mRNA are rapid; the stability of IL 3 mRNA is not affected by dexamethasone; hormone treatment does not inhibit either mRNA processing or transport from the nucleus. Our findings demonstrate that a set of mitogen-inducible genes in helper T cells can be subject to a second level of regulation mediated by glucocorticoid hormones. PMID- 2931481 TI - Two distinct classes of IgG Fc receptors on a human monocyte line (U937) defined by differences in binding of murine IgG subclasses at low ionic strength. AB - We have defined two distinct classes of IgG Fc receptors (FcR) on cells of a human monocytic line (U937) by analyzing the direct binding of murine IgG subclasses in medium of low ionic strength. Four lines of evidence support this contention. The binding of aggregated murine IgG2b (AggmIgG2b) to U937 and Daudi cells was enhanced at low ionic strength, whereas monomeric murine IgG2a (mIgG2a) did not bind to Daudi cells and its high affinity binding to U937 cells was unaffected by changes in ionic strength. Double reciprocal inhibition experiments with U937 cells indicated that the binding of both ligands was inhibited 30 to 135 times more efficiently by the homologous ligand than by the heterologous one. That is, the binding of 125I-AggmIgG2b was inhibited 50% by 3.5 micrograms/ml of AggmIgG2b and 100 micrograms/ml of mIgG2a. Similarly, the binding of 125I-mIgG2a was inhibited 50% by 2.5 micrograms/ml of mIgG2a and only 44% by 243 micrograms/ml of AggmIgG2b. A monoclonal antibody of the IgG2b subclass raised against an IgG FcR on K562 cells inhibited binding to U937 cells of AggmIgG2b but not of mIgG2a. Trypsinization of U937 cells abrogated by 32% the binding of mIgG2a but did not affect the binding of AggmIgG2b. Human IgG inhibited binding of both AggmIgG2b and mIgG2a to U937 cells. We propose that the newly recognized FcR that binds AggmIgG2b is the human homologue of the murine macrophage IgG2b/1 FcR (FcRII), and that the previously described 72,000 dalton high-affinity FcR on U937 cells that binds mIgG2a is the human equivalent of the murine macrophage IgG2a FcR (FcRI). PMID- 2931482 TI - Transepithelial transport of maternal antibody: purification of IgG receptor from newborn rat intestine. AB - In newborn rats, passive immunity is acquired from the mother by selective transport across the gut wall of immunoglobulin (IgG) present in colostrum and milk. Ultrastructural and physiologic studies of this mechanism have shown that the binding and uptake of IgG exhibits saturation kinetics and stereochemical specificity consistent with it being a receptor-mediated process. We report here the isolation and purification of a protein from membranes of neonatal rat enterocytes that binds immunoglobulins. The basis of our purification procedure is the extraction of this IgG-binding protein from isolated membranes in the absence of detergents and its biospecific elution from an IgG affinity column. This purified protein consists of two similar polypeptides of 52,000 and 48,000 Mr. The interaction of this purified protein with immunoglobulin is isotype dependent, with specificity for IgG and its Fc fragment, and pH dependent, with optimal binding at the intraluminal pH of 6.0. This intestinal IgG-binding protein is found in enterocytes of the proximal intestine during the early postnatal period, but is absent after weaning when transport of IgG ceases. Our results suggest that this purified intestinal IgG-binding protein functions in the transepithelial transport of IgG in rat neonates. PMID- 2931483 TI - Activation of the C3b receptor: effect of diacylglycerols and calcium mobilization. AB - The plasma membrane expression and the phagocytic function of the C3b receptor (CR1) on human neutrophils (PMN) are under the control of cellular regulatory mechanisms, and phorbol esters are one class of agents that modulate both membrane expression and function. Phorbol esters also activate protein kinase C; however, the physiologic activation of protein kinase C is thought to be mediated by diacylglycerol. Diacylglycerols are generated during phosphatidyl inositol turnover, which is associated with a rise in intracellular calcium due to another product of polyphosphoinositide metabolism, inositol trisphosphate. We therefore studied the effects of synthetic diacylglycerols and calcium mobilization on CR1 function. In our experiments, treatment of neutrophils with two synthetic diacylglycerols, 1-oleoyl-2-acetoyl-sn-3-glycerol (OAG) and sn-1,2 dioctanoylglycerol, like phorbol esters, induced ligand-independent internalization of CR1. In contrast, the addition of exogenous phospholipase C had no effect on receptor internalization over the time course studied. OAG treatment also enabled neutrophils to specifically phagocytose via CR1. Calcium mobilization with the calcium ionophore A23187 (1 microM) had a synergistic effect on phorbol ester-induced internalization of CR1, but abrogated the phorbol ester enhancement of CR1-dependent phagocytosis. Both trimethoxybenzoate, the intracellular calcium antagonist, and chlorpromazine inhibited phorbol ester induced internalization of CR1, whereas chelation of extracellular calcium did not. We conclude that activation of protein kinase C modulates the expression and function of CR1, and that calcium mobilization also influences these processes. We speculate that polyphosphoinositide turnover may be involved in the physiologic regulation of CR1. PMID- 2931484 TI - Induction of suppressor cells from peripheral blood T cells by 15 hydroperoxyeicosatetraenoic acid (15-HPETE). AB - 15-hydroperoxyeicosetetraenoic acid (15-HPETE), a lipoxygenase metabolite of arachidonic acid, inhibited polyclonal IgG and IgM production in pokeweed mitogen (PWM)-stimulated cultures of human peripheral blood mononuclear cells, whereas 15 hydroxyeicosetetraenoic acid (15-HETE) had little effect in this system. T cells preincubated for 18 hr with 15-HPETE caused substantial inhibition of IgG and IgM production of fresh, autologous B and T cells stimulated by PWM. The suppressive effect of the 15-HPETE-treated cells was lost if the cells were irradiated before the PWM culture, but not by treatment with mitomycin C. The suppressive effect was also lost if OKT8+ T cells were removed after, but not before, preincubation of the T cells with 15-HPETE. OKT8- T cells incubated with 15-HPETE for 18 hr showed a large increase in the percentage of cells staining with directly fluoresceinated Leu-2, another marker for suppressor cells. Thus, 15-HPETE induces functional and phenotypic suppressor cells from resting human peripheral blood T cells. PMID- 2931485 TI - Rapid purification of the human C3b/C4b receptor (CR1) by monoclonal antibody affinity chromatography. AB - The human C3b/C4b receptor (CR1) is a polymorphic glycoprotein that is expressed on erythrocytes, leukocytes and glomerular podocytes. Further structural analysis and molecular genetic studies would be facilitated by the availability of relatively larger amounts of purified CR1. Milligram quantities of CR1 were purified from erythrocyte membranes 10,000-fold with an average yield of 30-40% by a rapid procedure which utilized sequential chromatography on Matrex Red A and a monoclonal anti-CR1 antibody affinity column. The purified receptor was homogeneous by SDS-PAGE and consisted of the 2 most common alleles of CR1. Purified CR1 also retained its function of serving as a cofactor for the cleavage of C3b to iC3b, C3dg and C3c. The amino acid composition was typical of that of a globular protein and sequence analysis of the N-terminus of the purified CR1 revealed that it was blocked. PMID- 2931486 TI - Specificity of alloactivated human T lymphocyte clones in secondary proliferation, cell-mediated lympholysis and interleukin-2 release. AB - Alloreactive cytolytic T cell clones were generated from mixed leucocyte reactions (MLRs) between unrelated individuals. Two clones exhibited proliferative responses specific for class I HLA antigens B21 and B17. They were also found to be cytolytic toward cells bearing these HLA-B antigens as measured in cell-mediated lympholysis (CML) assays. Four clones exhibited primed lymphocyte test (PLT) and CML activity specific for various class II HLA antigens, namely DR1, DR5, DQw3 and DRw53. For each of these six clones, the CML specificity was identical to the PLT specificity. Both class I and class II specific clones released interleukin-2 (IL-2) upon restimulation with irradiated cells carrying the relevant HLA specificity. This stimulator-induced IL-2 release showed the same specificity pattern as that observed in the PLT assay. Monoclonal antibody (mAb) inhibition studies on alloreactive T cell clones showed similar inhibition profiles of PLT, CML and IL-2 release assays. These findings suggest that cytolytic activity, secondary proliferation and IL-2 release by alloactivated T cells may be induced by the same HLA encoded determinant. PMID- 2931487 TI - Regulatory function of Thy-1-negative cells: V. A lymphokine of B cell origin (BEF) induces in vitro high antibody response in genetically selected low responder mice. AB - Studies were conducted on two lines of mice genetically selected, respectively, for high (AB/H) and low (AB/L) antibody production, in order to identify the mechanism by which genes involved in the selection express their functions. It was found that B cell-derived enhancing factor (BEF), a lymphokine of B cell origin which acts on T cells by preventing the activation of suppressor cells, is effective in inducing high responses in low responder mice, whereas it is ineffective in modulating antibody production in high responder mice. As a result, no difference was found between the responses of AB/H and AB/L mice when spleen cells were stimulated in vitro in the presence of BEF. AB/H and AB/L mice do not seem to differ in their B cell functions since no difference was found in the capacity of B cells of either line to synthesize antibodies in the presence of T cell-replacing factor (TRF), or to produce endogenous BEF. These data indicate that, at least in vitro, the character of general responsiveness of these two mouse lines mainly reflects differential reactivity of T suppressor cells. Since the two lines represent, respectively, the maximal and minimal responsiveness of an outbred population of animals, it is suggested that the individual difference in antibody response is related to individual differences of T suppressor cells in responding to the immunogen. PMID- 2931488 TI - Fibronectin-mediated keratinocyte migration and initiation of fibronectin receptor function in vitro. AB - Cell suspensions of human keratinocytes, freshly isolated from skin specimens, did not express plasma fibronectin (pFN) receptor function in short-term assays for cell attachment and spreading on pFN-coated culture dishes and binding and phagocytosis of pFN-coated latex beads. These activities were expressed, however, by the cells harvested from primary keratinocyte cultures after 2-4 days of culture. Analysis of the cell types arising during primary culture, based on staining with antikeratin antibodies and bullous pemphigoid (BP) serum, revealed that about 90% of the originally isolated cell population consisted of keratinocytes (keratin-positive) and 30% were basal cells (BP antigen-positive). After 2 days of culture, 95% of the cells were keratinocytes and 70% were basal cells. In vitro initiation of pFN receptor function also was observed in cells harvested from epidermal explants. After 9 days in culture, the cells that migrated out of the explants also were active in short-term cell adhesion assays, while cells remaining in the central region of the explant had much less activity. In related studies, the role of pFN in epidermal cell migration was analyzed, and it was found that anti-pFN antibodies inhibited migration of keratinocytes out of epidermal explants. Addition of preimmune IgG, however, had no effect. It appears, therefore, that pFN is important in all aspects of keratinocyte adhesion, and the expression of pFN receptor function may be a critical activation step necessary for basal cell phagocytosis and migration during wound healing. PMID- 2931489 TI - Efficacy of ciprofloxacin in experimental arthritis caused by Escherichia coli- in vitro-in vivo correlations. AB - Ciprofloxacin, a new carboxyquinolone, has potent in vitro bactericidal activity against the major aerobic, gram-negative bacillary pathogens that cause human pyoarthroses. We investigated the in vivo efficacy of ciprofloxacin in a rabbit model of septic arthritis due to Escherichia coli. Animals received either ciprofloxacin (80 mg/kg per day) or gentamicin (5 mg/kg per day). Ciprofloxacin was rapidly bactericidal in vivo and was significantly more effective in reducing the numbers of E. coli in synovial tissue than was gentamicin at days 10 and 17 of therapy (P less than .0005 and P less than .05, respectively). Similarly, ciprofloxacin was significantly more active than was gentamicin in reducing the numbers of E. coli in joint fluid on day 10 of therapy (P less than .0005); however, by day 17 of therapy, the numbers of E. coli in joint fluid were not significantly different in the two therapy groups. Neither regimen was effective in preventing the development of postinfectious inflammatory synovitis. There was no in vivo development of resistance to either antibiotic during therapy. Ciprofloxacin therapy was associated with significantly higher bactericidal titers in serum and joint fluid than were observed with gentamicin therapy (P less than .0005). Ciprofloxacin warrants further in vivo evaluation in invasive E. coli infections. PMID- 2931490 TI - Immunoprophylaxis of infection with hepatitis B virus in infants born to hepatitis B surface antigen-positive carrier mothers. AB - Infants born to carrier mothers positive for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) received 5 micrograms of hepatitis B virus (HBV) vaccine on four occasions. Group 1 received vaccine only, group 2 received vaccine plus hepatitis B immune globulin (HBIG) at birth, and group 3 received vaccine plus HBIG at birth and at one month. Infants born to HBeAg-positive mothers (group 4) received a reduced dose of vaccine (2.5 micrograms) on three occasions as well as HBIG at birth. As compared with 78.4% of the control group (infants whose parents refused vaccination) who became chronic HBV carriers at the age of 14 months, the protective efficacy rate of vaccination was 75.3% in group 1,85.5% in group 2,89.7% in group 3, and 87.2% in group 4. HBV vaccine (5 micrograms) was also given to infants born to HBsAg-positive, HBeAg-negative mothers on four on four occasions. The antibody response to HBsAg in vaccine recipients was 12% after the first dose, 44% after the second dose, and 75% and 100% at six months and 1.5 years of age, respectively. PMID- 2931491 TI - Respiratory syncytial virus infection of human mononuclear leukocytes in vitro and in vivo. AB - Recurrent infections with respiratory syncytial virus (RSV) have been well documented despite serological evidence of prior exposure of the host and the absence of clear evidence of antigenic variation of the virus. Therefore, human mononuclear leukocytes, as well as purified lymphocytes and monocytes macrophages, were exposed to RSV in vitro and examined for expression of viral antigens by using indirect immunofluorescence with monoclonal antibodies to RSV. RSV infected both human monocytes-macrophages and lymphocytes in vitro. RSV infection resulted in both a decrease in the number of T helper phenotype cells and an increase in T suppressor phenotype cells. RSV proteins were disproportionately expressed by atypical or lymphoblastoid cells, many of which were of the T suppressor phenotype. Circulating mononuclear leukocytes obtained from symptomatic children infected with RSV frequently expressed viral antigens. Viral antigens appeared to be detected more frequently in cells from the younger subjects. The findings suggest that initial or early RSV infections in children include infection of circulating immunocompetent cells. It remains to be determined whether the described RSV-induced alterations in lymphocyte subpopulations contribute to recovery from and/or recurrence of RSV infections. PMID- 2931492 TI - Abnormality of glycoprotein Ib in two cases of "pseudo"-von Willebrand's disease. AB - Two unrelated patients with "pseudo" ("platelet-type")-von Willebrand's disease (vWD) are described demonstrating thrombocytopenia with a prolonged bleeding time, ristocetin-induced platelet aggregation at low stimulus concentrations, decreased levels of ristocetin-cofactor activity (vWF:RCo), slight cryoprecipitate-induced platelet aggregation in the absence of ristocetin, and a lack of the high molecular weight factor VIII-von Willebrand factor (FVIII/vWF) multimers in plasma. Isolated washed patient platelets bound more FVIII/vWF at high (1 and 0.75 mg/ml) and low (0.5 and 0.25 mg/ml) ristocetin concentrations than control platelets. Fresh or paraformaldehyde-fixed washed platelets from these patients also bound more specific monoclonal antibody to glycoprotein Ib (25,000 binding sites per cell) than normal platelets (15,000 +/- 3,300 binding sites per cell). Results obtained in control patients with thrombocytopenia and increased platelet size (May-Hegglin anomaly and vWD type IIB) excluded a nonspecific increase of glycoprotein Ib in the platelets of the patients with pseudo-vWD. These data indicate that in pseudo-vWD, the primary abnormality lies in the platelet and is related to a quantitative and/or qualitative anomaly of platelet membrane glycoprotein Ib. PMID- 2931493 TI - Dental problems of the sickle cell anemia patient. PMID- 2931494 TI - Hydrolysis of deoxycorticosterone-21-yl sulphate and dehydroepiandrosterone sulphate by microsomal preparations of human placentae: evidence for a common enzyme. AB - The human placenta can hydrolyse both dehydroepiandrosterone-3 beta-yl sulphate (DHASO4-) and deoxycorticosterone-21-yl sulphate (DOCSO4-). There is some uncertainty as to whether the same or different enzymes are responsible for hydrolysis of these substrates. As a fresh approach to this problem we have compared the quantities of DHASO4- and DOCSO4- hydrolysed by microsomal preparations of placentae obtained from 14 normal pregnancies and from 14 pregnancies complicated by steroid sulphatase deficiency. Under the conditions used, and standardizing the results to unit time and quantity of protein, 1380 8830 fmol DHASO4- were hydrolysed by 14 normal placentae whereas less than 1000 fmol DHASO4- were hydrolysed by the other 14 placentae, thereby designated as steroid sulphatase deficient. Net hydrolysis of DOCSO4- by the preparations of normal tissue was 9-52 fmol; hydrolysis of this substrate by steroid sulphatase deficient tissues was indistinguishable from that by boiled tissue (less than 29 fmol). Thus preparations of placentae which hydrolysed DHASO4- also hydrolysed DOCSO4-; tissues which did not hydrolyse DHASO4- also failed to hydrolyse DOCSO4 . The quantities of DHASO4- and DOCSO4- hydrolysed by the 28 individual placentae showed a positive correlation (r = 0.91, P less than 0.001). The apparent Michaelis constants for hydrolysis of DHASO4- and DOCSO4- were 38 and 274 mumol/l respectively. These results are consistent with the proposal that these substrates are hydrolysed by a common enzyme. PMID- 2931495 TI - Binding of glucocorticoid to the androgen receptor of mouse submandibular glands. AB - An increase in esteroprotease activity, a known cytodifferentiating response to androgen in the submandibular gland, occurred after cortisol acetate, dexamethasone or methyltrienolone (R1881) treatment in castrated genetically normal male (X/Y-castrated) mice, but not in normal male (X/Y) and testicular feminized male (Tfm/Y) mice. A peak with specific binding for [3H]cortisol appeared in sucrose density gradient patterns of extracts from X/Y-castrated mice and in almost the same fraction number as that for [3H]R1881 binding. However, peaks specific for neither [3H]cortisol nor [3H]R1881 binding were observed in Tfm/Y mice. The peak binding [3H]cortisol in extracts from X/Y-castrated mice, as well as the one binding [3H]R1881, were inhibited by unlabelled R1881 and cyproterone acetate, an antiandrogen; the peak was not, however, affected by unlabelled oestradiol-17 beta. The binding capacity of [3H]cortisol determined by Scatchard analysis was similar to that of [3H]R1881 (103 and 106 fmol/mg protein respectively). The Kd value of [3H]cortisol, however, was about 13.6-fold higher than that of R1881. These results suggest that cortisol has the ability to promote androgenic cytodifferentiating action in the mouse submandibular gland by binding to its androgen receptors, if androgens are absent or deficient. PMID- 2931496 TI - Periradicular surgery following bilateral total hip replacement. PMID- 2931497 TI - Helper T cells reacting to idiotype on IgG but not IgM. AB - Immunization with an IgG1 but not an IgM monoclonal anti-NP (4-hydroxy-3 nitrophenyl acetyl) antibody induced idiotype-recognizing T helper cells, although these two antibodies carry the same variable regions. The T cells appear to react to an idiotype on the IgG1 but not the IgM antibody. They selectively enhance the expression of that idiotype in the IgG1 fraction of an in vitro anti NP response. PMID- 2931498 TI - Children's Medical Services: Florida's expanded Crippled Children's Program from the 1920s to the 1980s. PMID- 2931499 TI - Phosphoglucomutase and esterase D activity in post-coital vaginal swabs. PMID- 2931500 TI - Unconventional pathogens causing spongiform encephalopathies absent in blood products. AB - To determine whether unconventional pathogens causing subacute spongiform encephalopathy may be present in blood products, a newly developed hepatitis B vaccine and a widely used blood product were injected into mice and rats. As only a few aged mice in the test and the control groups showed spongiform encephalopathic change of a sparse or mild degree and which differed from that seen in rodents infected with Creutzfeldt-Jakob disease, the presence of unconventional pathogens in the tested inocula can be ruled out. PMID- 2931501 TI - Activity of spindle afferents from cat anterior thigh muscles. I. Identification and patterns during normal locomotion. AB - The naturally occurring activity patterns of anterior thigh muscle spindle afferents were recorded during unrestrained treadmill locomotion by means of floating microelectrodes chronically implanted in the fifth lumbar dorsal root ganglion. Conduction velocity of units from primary and secondary endings was determined by spike-triggered averaging of the signals from a chronically implanted nerve cuff. Activity from knee extensor muscle spindles generally occurred during periods of muscle lengthening, but was often greater for small stretches when the muscle was active (during stance phase of walking) than for larger stretches when the muscle was passive (swing phase), indicating fusimotor enhancement of spindle sensitivity in phase with extrafusal muscle recruitment. Activity from spindles in biarticular muscles acting across the knee and hip was more variable and complex than that seen in the pure knee extensors, and frequently included activity during rapid muscle shortening (swing phase) indicative of strong static fusimotor input. Changes in speed of gait caused changes in the range and velocity of muscle length excursions monitored by chronically implanted length gauges, but such changes were accompanied by only modest changes in spindle afferent activity, suggesting concurrent and compensatory changes in fusimotor influence on spindles. Activity from spindle secondary endings was generally lower, more regular, and less velocity dependent than that from primary endings, consistent with their lack of input from the dynamic fusimotor apparatus. The activity of all spindle afferents studied was similarly well modulated during extrafusal activity of the parent muscles, regardless of the kinematic conditions of muscle length and velocity during which this muscle work occurred. This suggests that the fusimotor apparatus is well orchestrated to regulate the static and dynamic sensitivity of primary spindle afferents at levels appropriate to the anticipated motion. PMID- 2931502 TI - Activity of spindle afferents from cat anterior thigh muscles. II. Effects of fusimotor blockade. AB - Chronically implanted electrodes and nerve cuff catheters were used to record the activity of individual muscle spindle afferents during treadmill walking as low doses of lidocaine were infused around the femoral nerve to progressively block gamma motoneuron activity. Both primary and secondary endings from both the monarticular knee extensors and the biarticular hip/knee muscles of the anterior thigh showed large decreases in afferent activity, usually well before changes in the electromyographic activity, force output, or length and velocity were seen in the parent muscles. This decline in the proprioceptive signal feeding back onto the spinal cord, which we presume to have involved most of the spindles supplied by the femoral nerve, did not cause noticeable irregularities or instability of the walking gait. At the peak of the fusimotor blockade, spindle afferents from knee extensor muscles lost about half of their usually brisk activity during the near-isometric contraction of the stance phase. Significant decreases in the response to passive stretch during the flexion phase also occurred. At the peak of the fusimotor blockade, spindle afferents from the biarticular muscles lost all of their activity during the rapidly shortening swing phase and about half of their activity during the rapidly lengthening stance phase. For both monarticular and biarticular muscle spindles, the activity decreases in stance and swing phase often occurred at distinctly different stages of the progressive fusimotor blockade, indicating several different sources of fusimotor control. From these data, we infer that the sensitivity of most spindle afferents is substantially influenced by fusimotor activity during phases of both extrafusal activity and extrafusal silence. At least some of this influence appears to come from fusimotor neurons whose recruitment is independent of the extrafusal recruitment. The extent and type of fusimotor effects on spindle afferent sensitivity (dynamic or static) appear to be specialized for the mechanical events that tend to occur during those phases. PMID- 2931503 TI - Activity of spindle afferents from cat anterior thigh muscles. III. Effects of external stimuli. AB - Chronically implanted electrodes were used to record the activity of identified single muscle spindle afferents in awake cats during responses to various types of manual and electrical stimulation. During vigorous cyclical responses such as shaking and scratching, spindle afferents generally maintained at least some activity during both lengthening and shortening of the parent muscle, indicating that the programs for these movements include both extra- and intrafusal recruitment. During noncyclical responses such as ipsilateral limb withdrawal and crossed-extension, spindle activity was modest and poorly correlated with extrafusal activity. Weak cutaneous nerve shocks during walking elicited complex excitatory and inhibitory phase-dependent reflexes in the various muscles studied but caused relatively little change in spindle afferent activity, indicating a lack of correlation between alpha and gamma motoneuron activity. A primary and a secondary afferent from sartorius muscle were recorded simultaneously during walking cycles that were perturbed by electrically induced twitches of the antagonist hamstring muscles; both demonstrated highly sensitive, short latency responses to the resulting skeletal motion, consistent with their previously suggested roles in detecting small brief mechanical perturbations. The degree to which fusimotor responses were correlated with extrafusal responses to somatosensory perturbations was highly dependent on the specific nature of the stimulus and the response. Fusimotor reprogramming of the spindle sensitivity appears to be a feature of cyclical movements that are presumably under proprioceptive control, whereas brief perturbations within the context of a particular motor program may be ignored by the fusimotor system. PMID- 2931504 TI - Peripheral myxoma of the right maxilla: a case and review of the Japanese literature. PMID- 2931505 TI - The predictive value of hepatic artery perfusion scintigraphy. AB - A case in which hepatic artery perfusion scintigraphy (HAPS) correctly predicted the outcome of chemotherapy in a patient with metastatic liver disease is presented. In spite of angiography showing "proper" position of the Infusaid catheter, HAPS showed preferential perfusion to the right lobe of the liver. Computed tomography pre- and postchemotherapy showed a changing pattern of the metastatic foci correlating with the perfusion demonstrated by HAPS. PMID- 2931506 TI - Myofibroblast activity of radial scars. AB - Radial scars from 38 cases, comprising 12 associated with cancer and 26 with benign lesions, have been examined by electron microscopy. One-third of the lesions, regarded as being at an early stage of development, showed abundant spindle cells, which displayed the ultrastructural characteristics of myofibroblasts. These included many profiles of endoplasmic reticulum, prominent myofilaments and a close association with collagen and elastic fibres. The remaining 'mature' radial scars showed relatively few myofibroblasts, sparsely distributed in the stroma. The stromal cells associated with the 'early' lesions were seen in close proximity to degenerating parenchymal structures, which frequently showed loss of basal lamina. Obliteration of the central parenchymal component appeared to be a prominent feature of radial scar formation. The ultrastructural appearances are consistent with a progressive development of the lesion, associated with sporadic myofibroblast activity. PMID- 2931507 TI - Combined salbutamol and ipratropium bromide by inhalation in the treatment of severe acute asthma. PMID- 2931508 TI - Fibrosarcoma in a girl with celiac disease and IgA deficiency. AB - A case of abdominal wall fibrosarcoma in a 17-year-old girl with celiac disease and IgA deficiency is described. Celiac disease was putatively diagnosed with intestinal biopsy at the age of 15 years when she came for hospital investigations because of IgA deficiency and recurrent respiratory infections. The tumor occurred at the age of 17 years during the gluten challenge performed for final diagnosis of celiac disease. Surgical excision, irradiation, and chemotherapy were initially successful. After 7 months, however, the tumor recurred. Reoperation and a new course of irradiation therapy coinciding with the reinstitution of a gluten-free diet proved to be effective in tumor eradication. Nine years after the cessation of cancer treatment she is well and has two healthy children. PMID- 2931509 TI - Respiratory insufficiency in newborns with abdominal wall defects. AB - Respiratory failure in newborns with abdominal wall defects has been attributed to increased intra-abdominal pressure and elevation of the diaphragm after closure. Despite surgical techniques designed to minimize intra-abdominal pressure, we have observed prolonged respiratory insufficiency in several such infants. We reviewed the charts of 108 infants from 1975 to 1982 who had abdominal wall defects: 53 with gastroschisis, 29 with small omphaloceles, 22 with liver-containing or giant omphaloceles (GO), and four with cloacal exstrophy. Nine infants with GO (41%) had prolonged respiratory insufficiency and five died. Infants with GO required longer periods of oxygenation and ventilation (P less than .001, ANOVA) than infants with other abdominal wall defects. Clinical observation suggested that infants with GO have a small, narrow thorax. We obtained detailed measurements from the chest radiographs of infants in all groups. After correction for birth weight, babies with GO had smaller chest widths (P less than .001) and lung areas (P less than .05) than infants with other abdominal wall defects. At autopsy, one newborn with GO was found to have severe pulmonary hypoplasia. Prolonged respiratory insufficiency in infants with GO may be explained by pulmonary hypoplasia and/or by a narrow chest deformity which limits lung expansion. PMID- 2931510 TI - The missing link in the pathogenesis of gastroschisis. AB - Is gastroschisis embryologically distinct from omphalocele or simply a ruptured small omphalocele (hernia of the umbilical cord)? Serial sonographic imaging of a fetus with a small omphalocele at 27 weeks gestation has now provided the "missing link" in the pathogenesis of gastroschisis by documenting in utero rupture resulting in a gastroschisis. PMID- 2931511 TI - Ultraviolet light-induced yellowing of dental restorative resins. PMID- 2931512 TI - Laparoscopic sterilization in camps and institutional set-up. PMID- 2931513 TI - Anorexia nervosa and the adrenal: the effect of weight gain. AB - Cortisol (F) and dehydroepiandrosterone (DHA) were measured following each 5 kg gain in weight in a group of 16 patients with anorexia nervosa admitted to hospital for refeeding. The mean percentage of standard weight on admission was 65% and that on discharge was 92%. Basal plasma cortisol fell gradually throughout the inpatient period, the correlation coefficient of the regression line relating percentage of standard weight to plasma cortisol in all patients was -0.559 (p less than 0.001). Adrenal androgen production, however, increased with weight gain and the correlation coefficient of the regression line of androgen production against percentage of standard weight was +0.303 (p less than 0.01). The DHA/F ratio increased with weight gain. This suggests that weight gain in the patient with anorexia nervosa could be associated with increased activity in the adrenal 17,20-lyase enzymes and a decrease in the activity of the 3-beta hydroxysteroid dehydrogenase. The possibility that these adrenal enzyme changes are controlled by pituitary proopiocortin peptides [the putative cortical androgen stimulating hormone (CASH)] is discussed as is the relationship between normal adrenarche and the weight related changes in adrenal function in anorexia nervosa. PMID- 2931514 TI - Structural alteration of the membrane of erythrocytes infected with Plasmodium falciparum. AB - Human erythrocytes infected with five strains of Plasmodium falciparum and Aotus erythrocytes infected with three strains of P. falciparum were studied by thin section and freeze-fracture electron microscopy. All strains of P. falciparum we studied induced electron-dense conical knobs, measuring 30-40 nm in height and 90 100 nm in diameter on erythrocyte membranes. Freeze-fracture demonstrated that the knobs were distributed over the membrane of both human and Aotus erythrocytes. A distinct difference was seen between the intramembrane particle (IMP) distribution over the knobs of human and Aotus erythrocyte membranes. There was no change in IMP distribution in infected human erythrocyte membranes, but infected Aotus erythrocytes showed an aggregation of IMP over the P face of the knobs with a clear zone at the base. This difference in IMP distribution was related only to the host species and not to parasite strains. Biochemical analysis demonstrated that a higher proportion of band 3 was bound to the cytoskeleton of uninfected Aotus erythrocytes than uninfected human erythrocytes after Triton X-100 extraction. This may account for the different effects of P. falciparum infection on IMP distribution in the two different cell types. PMID- 2931515 TI - The use of polydioxanone suture in midline incisions. PMID- 2931516 TI - Plasma concentrations of testosterone, dihydrotestosterone, delta 4 androstenedione, dehydroepiandrosterone and oestradiol-17 beta in the crab-eating monkey (Macaca fascicularis) from birth to adulthood. AB - Plasma testosterone, 5 alpha-dihydrotestosterone (DHT), delta 4-androstenedione, dehydroepiandrosterone (DHA) and oestradiol-17 beta concentrations of crab-eating macaques after birth were analysed by RIA. The profiles of plasma testosterone and DHT exhibited four phases: (1) a neonatal phase (0 to 3-4 months of age) with considerable synthetic testicular activity; (2) a phase of 'infancy' (generally up to 29 months of age) during which the values of both androgens were low; (3) a prepubertal phase (generally up to 43 months of age) when circulating values oscillated with wider individual variations, and (4) a pubertal phase when the concentrations increased in parallel and concomittantly with the onset of meiosis and the establishment of spermatogenesis. The testosterone values continued to increase, reaching adult values at about 5-6 years of age, whereas DHT levels tended to stabilize from 4-5 years. Relatively high androstenedione values during the neonatal phase decreased progressively until puberty, then increased again slowly up to the adult stage when they plateaued at about neonatal levels. The DHA levels were high during the first months, decreased at about 1 year, remained stable during infancy and prepuberty and then declined again during puberty. At about 5 years, the values were 28% of those in neonates. There was no evidence of an adrenarche before the first signs of sexual maturity were observed. Oestradiol 17 beta concentrations were high at birth and until 3 months, then decreased and remained steady from 1 year of age until adulthood, except at the onset of puberty (27-30 months of age) when high values were again noted. Our results show that, during the neonatal period, the testis exhibited considerable secretory activity. PMID- 2931517 TI - Long-term reversible suppression of oestrus in bitches with nafarelin acetate, a potent LHRH agonist. AB - Adult cyclic beagle bitches were treated for up to 18 months with nafarelin acetate via subcutaneously implanted osmotic pumps, starting during the first week of a pro-oestrous vaginal discharge. The imminent ovulation appeared to be unaffected by treatment, but doses of 8 or 32 micrograms analogue/day reduced the integrated luteal progesterone values. No new oestrus was detected in 3 bitches during 18 months of treatment with 32 micrograms/day, which resulted in mean plasma levels of 0.4 ng analogue/ml. A return to oestrus was observed in all 3 bitches between 3 and 18 weeks after cessation of treatment: 2 of the bitches mated at those times and produced normal litters. Another 2 bitches were similarly treated with 32 micrograms analogue/day; they were mated at the oestrus at start of treatment and dosing was continued for about 63 days. One of the bitches conceived and produced a normal litter. Nafarelin acetate treatment begun during anoestrus resulted in an induced heat 1-2 weeks after the start of treatment. The induced heat consisted of pro-oestrous vaginal discharge, oestrous vaginal cytology, and ovulation (judged by increased circulating levels of progesterone). Three bitches mated at the induced heat and treated for the normal duration of gestation did not litter. Nafarelin treatment of 3 bitches before puberty did not induce signs of oestrus and prevented the occurrence of oestrus through 18 months of treatment. The first oestrus in these bitches occurred 3.5-4 months after cessation of treatment, but mating at that time did not result in pregnancy. These studies have established the feasibility of and dosage requirement for the use of the LHRH agonist as a contraceptive in the bitch. PMID- 2931518 TI - The Fitz-Hugh-Curtis syndrome revisited. Changing perspectives after half a century. AB - The Fitz-Hugh-Curtis syndrome is an extrapelvic manifestation of pelvic inflammatory disease. Classically it consists of adhesions between the liver capsule and the diaphragm or the anterior peritoneal surface. Two recent changes have been made in the assessment of this syndrome. One, the syndrome was originally thought to be caused solely by Neisseria gonorrhoeae. Recent studies using tissue cultures and serum antibody titers have documented a major etiologic role for Chlamydia trachomatis as well. Two, the condition has recently been reported to exist in men, whereas previously it was believed to be limited to sexually active women in their reproductive years. PMID- 2931519 TI - Modulation of macrophage-lymphocyte interactions by the antiarthritic gold compound, auranofin. AB - Auranofin (AF), a new oral gold agent effective for treating rheumatoid arthritis (RA) was evaluated for its ability to alter macrophage and lymphocyte functions of immune mediated chronic inflammation. AF (2 microM) inhibited antigen presentation by splenic macrophages to sensitized (DNFB) lymph node cells in vitro and also inhibited production of IL-2 and IL-1 by lymphocytes and macrophages, respectively. When AF suppressed Con-A induced mitogenesis in vitro, there were no inhibitory effects on Con-A induced suppressor T cell functions. AF administered orally to normal mice did not affect antigen presentation. DNFB contact sensitivity or Con-A induced mitogenesis. High concentrations of topical AF inhibited local immune responses to contact sensitizing agents and enhanced the induction of antigen specific suppressor T cells. Optimally, in vitro or in vivo AF inhibited macrophage and helper T cell functions with impairing the induction of suppressor T cells. After chronic treatment, similar effects could contribute to the efficacy of AF in humans with RA. PMID- 2931520 TI - Familial alterations of immunoregulation in systemic lupus erythematosus. AB - To better define the relationship between suppressor cell function and number and disease expression, the immunoregulatory profiles of 12 probands with systemic lupus erythematosus (SLE) and 34 of their asymptomatic family members were studied, using concanavalin A induced suppressor cells for functional analysis. SLE family members as a whole showed no impairment of mean suppressor levels, although 7 of 34 had altered suppression of DNA synthesis and 5 of 34 had altered suppression of IgG synthesis. Ratios of OKT4/T8 T cell subsets showed no difference between the study population, although 3 SLE family members had an increased ratio (greater than 2 SD) relative to controls. The 12 family members with either altered suppressor cell number or function had higher antibody levels to dRNA (Poly A . U) than did those with normal suppressor function and number. The results demonstrate that altered suppressor cell number and function occur in certain asymptomatic family members of SLE patients and may be weakly associated with markers of a preceding RNA viral infection. PMID- 2931521 TI - Decrease in the reaction of DNA repair synthesis in response to nicotinamide or 3 aminobenzamide in ultraviolet irradiated systemic lupus erythematosus lymphocytes. AB - Systemic lupus erythematosus (SLE) lymphocytes failed to accelerate ultraviolet (UV) induced DNA repair synthesis normally observed following inhibition of poly(adenosine diphosphoribose) polymerization. Without inhibitors of poly(adenosine diphosphoribose) polymerase such as nicotinamide or 3 aminobenzamide, DNA repair synthesis following UV irradiation was found to occur normally in the cells of patients. These data suggest that DNA repair is disturbed under special conditions in the lymphocytes of SLE patients. PMID- 2931523 TI - Handicapped people in Hong Kong: the problems of access to dental care. PMID- 2931522 TI - The clinical significance of coagulation abnormalities in systemic sclerosis (scleroderma). AB - A coagulation screen and measurement of circulating factor VIII related antigen (VIII-RAg), factor VIII coagulant activity (VIII-C) and beta-thromboglobulin (beta TG) levels were carried out in 25 patients with systemic sclerosis and 25 age and sex matched controls. Both VIII-RAg and beta TG levels were significantly higher in the systemic sclerosis patients than controls. Fibrin degradation products were increased in 11 (44%) of the patients. There was a significant correlation between the VIII RAg/VIII-C ratio and severity of the vascular abnormalities noted on nailfold capillary microscopy. Those with VIII-RAg levels in excess of 200% of controls (10 of 25) had more severe disease with greater mean number of organ systems involved. PMID- 2931524 TI - The histamine H2 receptor agonist impromidine: synthesis and structure-activity considerations. AB - Impromidine (1) is a potent and selective histamine H2 receptor agonist and its structure comprises a strongly basic guanidine group containing two different imidazole-containing side chains. In this paper we report the synthesis of analogues in which both of the side chains and the guanidine group are modified and tested as agonists or antagonists at histamine H2 receptors on guinea pig atrium. A protonated amidine group linked by a chain of three carbon atoms to a tautomeric imidazole ring appears to be an essential feature for agonist activity and it is suggested that the second imidazole-containing side chain in impromidine mainly contributes toward affinity for histamine H2 receptors. PMID- 2931525 TI - A versatile speech output communication aid. AB - A portable, battery-powered communication aid with speech output, which can be operated by patients with limited finger control, is described. The device is sufficiently versatile to try out different methods of selection of words or phrases in the search for an acceptable, portable communication aid for the speech impaired. PMID- 2931526 TI - Lysogenicity of methicillin-resistant strains of Staphylococcus aureus. AB - The lysogenic status of 23 strains of methicillin-resistant Staphylococcus aureus, isolated at the Royal Prince Alfred Hospital, Sydney, since 1980, was studied. Twenty strains, belonging to the four predominant phage types isolated in this hospital, carried the same lysogenic phage which we have designated C. Three other phages were isolated from five strains belonging to phage type 84/85/90. The presence of phage C had little effect on the phage-typing pattern of the strains. Similarly, lysogenization with the other three phages did not result in a significant change in phage-typing patterns. However, when strain 1489, isolated in 1969, was lysogenized with these three phages, there was a change in phage-typing pattern. Lysogenization of this strain with phage 47T resulted in a marked loss of sensitivity to both group-I and group-III phages. The lysogenic status of these methicillin-resistant strains of S. aureus was compared with that of strains isolated between 1967 and 1970. There was no evidence that the strains isolated recently were either related to, or derived from, the earlier ones. PMID- 2931527 TI - Transfer of plasmid-borne aminoglycoside-resistance determinants in staphylococci. AB - Aminoglycoside-resistance determinants in staphylococci are borne on conjugative and non-conjugative plasmids. The conjugative plasmids were found in methicillin resistant strains of Staphylococcus aureus isolated recently in Darwin and Sydney, Australia and in Houston, Texas, USA. These plasmids and the class-2 conjugative plasmid reported by Archer and Johnston (1983) had similar patterns of EcoR1 restriction-endonuclease fragments, encoded resistance to gentamicin, kanamycin and neomycin, transferred to a non-lysogenic recipient in conditions that promoted close cell-to-cell contact and mobilised a small, non-conjugative plasmid. A further plasmid, pWG14, encoding resistance to kanamycin, neomycin, streptomycin, erythromycin and lincomycin, also displayed conjugative properties but did not mobilise the small, non-conjugative plasmid. The transfer frequency of all conjugative plasmids was stimulated by the addition of polyethylene glycol, particularly at concentrations above 20%, to mixtures of donor and recipient broth cultures. Polyethylene glycol appeared to promote close cell-to cell contact between donor and recipient cells. A representative of the most common aminoglycoside-resistance plasmids in Australian isolates of methicillin resistant S. aureus was non-conjugative and transferred by a bacteriophage mediated system to a lysogenic recipient. With the exception of plasmid pWG14, the conjugative plasmids were also transferred by a bacteriophage-mediated system. Furthermore, cultural conditions that favoured conjugative transfer of plasmids inhibited bacteriophage-mediated transfer and vice versa. The efficacy of the two transfer systems for analysing the plasmids of gentamicin-resistant, methicillin-resistant isolates of S. aureus has been compared. PMID- 2931528 TI - Study of the diurnal variation of human lymphocyte subsets. AB - The diurnal variation of peripheral white cells and in particular of different lymphocyte subsets has been investigated in 11 normal subjects. Monoclonal antibodies (Mab) phenotyping total T lymphocytes (UCHT1), cytotoxic/suppressor (UCHT4), helper T cells (Leu 3a), B lymphocytes (231) and K/NK cells (H25) have been used. In addition to the traditional parametric statistics, the chronobiological approach of cosinor was adopted in order to inferentially obtain the waveform covering the 24-hr period. Cosinor analysis validated the existence of a significant rhythm for leucocytes (p = 0.04, lymphocytes (p = 0.03), and Leu 3a positive cells (p = 0.04). The best fitting period was equal to 28 hr. No circadian rhythm was documented for lymphocyte subsets positive for Mab UCHT4, 231, H25, by testing the variability with a frequency ranging from 1 cycle every 12hr to 1 cycle every 28 hr. By the non-inferential analysis of temporal curves, a significant peak of Leu 3a positive cells at 20.00 hr (p less than 0.001) was observed. The acrophase has been recorded by cosinor analysis at 20.36 hr. We conclude that the circadian variability of Leu 3a positive cell profile must be taken into account when the helper/suppressor ratio is calculated. The time dependence of this lymphocyte subpopulation suggests that when therapy with corticosteroids is considered in autoimmunity, it should be planned by keeping the peak of Leu 3a positive cells as a marker time. PMID- 2931529 TI - Modulation of the immunoreactivity of a T-lymphocyte subpopulation by neutrophil released prostaglandin. AB - The effect of polymorphonuclear leukocytes (PMNs) on lymphocyte subpopulations and their reactivity was investigated by adding supernatants obtained by culturing PMNs with allogeneic or autologous lymphocytes which had been pre treated with prostaglandin (PG) synthetase inhibitors. PMNs were obtained from 12 healthy individuals, 7 patients with systemic lupus erythematosus (SLE) and 6 patients with bacterial infections. Freshly prepared normal lymphocytes pretreated with PG synthetase inhibitors were incubated with the above supernatants, and the lymphocyte and T-lymphocyte subpopulations were then quantitated, the responses of lymphocytes to mitogens measured and the generation of helper and suppressor T-cell activities for PWM-stimulated cultures assessed. We also ascertained which T-cell population, i.e. OKT4+ or OKT8+ cells, which had been altered by incubation with supernatants, was responsible for the suppressor T-cell activity. A reduced per cent of OKT4+ cells; depressed responses to Con A, PHA, PWM and allogeneic lymphocytes, impaired helper T-cell activity; and increased suppressor T-cell activity were noted after incubation of lymphocytes with supernatants. The percentage of T lymphocytes and of OKT8+ cells was, however, not affected. Further, enhanced suppressor T-cell activity was obtained when supernatant-incubated OKT4+ cells were cultured with OKT8+ cells, regardless of whether the latter had previously been exposed to supernatants. Addition of PG inhibitors to PMN co-cultures nearly restored the original percentage and reactivity of the T-lymphocyte populations, indicating a role for PG released from PMNs in the effects observed. The amount of PG demonstrated in co-culture supernatants was 30 times more than obtained by sonification of fresh PMNs and 10 times more than found in the culture medium containing PMNs alone. These results suggest that, besides monocytes, other phagocytes, including PMNs, can modulate lymphocyte-mediated immune reactivity by the release of PG. Deceased number of OKT4+ cells, impaired helper T-cell activity and enhanced suppressor cell activity may, at least in part, result from the effect of PG released from PMNs as well as monocytes. PMID- 2931531 TI - Complement, antigen-antibody complexes and immune complex disease. PMID- 2931532 TI - Cell-mediated lympholysis (CML) to allogeneic and trinitrophenyl (TNP)-modified cells: re-evaluation of the role of the thymus in CML. AB - The role of the thymus in cell-mediated lympholysis (CML) to allogeneic and trinitrophenyl (TNP)-modified cells was re-evaluated using adult thymectomized (ATx) and neonatal thymectomized (NTx) mice. CML to TNP-modified cells was used as the model of the major histocompatibility complex (MHC)-restricted CML. CML to TNP-modified cells, but not to allogeneic cells was reduced at late stages after ATx and remained low even in NTx-11 (thymectomy at 11 days of age) mice. Interleukin-2 (IL-2) producing activity in such mice was lower than that in the normal controls, while allogeneic CML was maintained at the same level as seen in the controls. The addition of exogenous IL-2 to in vitro culture led to a restoration of the generation of CML to TNP-modified cells, in neonatal thymectomized mice. These results suggested that thymus-dependency differs in the 2 forms of CML and that the CML to TNP-modified cells showed a higher thymus dependency than did the allogeneic CML. Moreover, the activity of helper T cells may exert a direct influence on CML to TNP-modified cells, as compared to allogeneic cells. PMID- 2931530 TI - Phenotypic and functional correlations in circulating lymphocytes of prodromal homosexuals and patients with AIDS. AB - Findings of selected phenotypic and functional parameters demonstrated significant aberrations in both prodromal homosexual males and patients with AIDS. An impaired blastogenic response to T-cell dependent B-cell mitogen was associated with a significant decrease in percentage of helper T cells but appeared unrelated to the percentage of suppressor T cells. The functional subsets of the latter were further defined by a panel of monoclonal antibodies (Leu8, Leu15, and HLA-DR) applying dual color flow cytometric techniques. In both homosexuals at risk and in AIDS patients, activated suppressor cells with the phenotype Leu2+Leu15+ and Leu2+HLA-DR+ were elevated while the reciprocal cytotoxic Ts cells (Leu2+Leu15- and Leu2+HLA-DR-) were depressed. Both subsets of suppressor precursor cells and effector cells (Leu2+Leu8+ and Leu2+Leu8-) were elevated particularly in high risk homosexual males. These results suggest a defective feedback loop that regulate both helper and suppressor T cells as well as B-lymphocyte functions and may explain the clinical manifestation of AIDS. PMID- 2931533 TI - Pyrimidine dimers are not the principal pre-mutagenic lesions induced in lambda phage DNA by ultraviolet light. AB - Experiments were performed to examine the role of cyclobutyl pyrimidine dimers in the process of mutagenesis by ultraviolet (u.v.) light. Lambda phage DNA was irradiated with u.v. and then incubated with an Escherichia coli photoreactivating enzyme, which monomerizes cyclobutyl pyrimidine dimers upon exposure to visible light. The photoreactivated DNA was packaged into lambda phage particles, which were used to infect E. coli uvr- host cells that had been induced for SOS functions by ultraviolet irradiation. Photoreactivation removed most toxic lesions from irradiated phage, but did not change the frequency of induction of mutations to the clear-plaque phenotype. This implies that cyclobutyl pyrimidine dimers can be lethal, but usually do not serve as sites of mutations in the phage. The DNA sequences of mutants derived from photoreactivated DNA showed that almost two-thirds (16/28) were transitions, the same fraction found for u.v. mutagenesis without photoreactivation. These results show that in this system, the lesion inducing transitions (the major type of u.v. induced mutation) is not the cyclobutyl pyrimidine dimer; a strong candidate for a mutagenic lesion is the Pyr(6-4)Pyo photoproduct. On the other hand, photoreactivation of SOS-induced host cells before infection with u.v.-irradiated phage reduced mutagenesis substantially. In this case, photoreversal of cyclobutyl dimers serves to reduce expression of the SOS functions that are required in the process of targeted u.v. mutagenesis. PMID- 2931534 TI - Cardiac morphology in rats with growth hormone-producing tumours. AB - Cardiac enlargement and dysfunction are common in patients with acromegaly. Whether these changes are a direct consequence of growth hormone excess is obscured by the high frequency of hypertension, diabetes mellitus, or atherosclerosis in acromegalic patients. In this study, the effects of chronic elevations of growth hormone (GH) upon the heart were studied in rats with GH producing tumours implanted subcutaneously for 4 weeks. Geometric measurements and histology were employed to detect the presence of cardiac changes. Increased mass was observed in the tumour-bearing animals. When compared with controls, in tumour-bearing rats there were significantly greater (P less than 0.05) right (0.17 +/- 0.03 v. 0.13 +/- 0.01 g) and left (0.62 +/- 0.05 v. 0.50 +/- 0.04 g) ventricular weights, external cardiac dimensions, and myocardial fibre diameters (9.4 +/- 0.6 v. 8.3 +/- 0.4 micron). However, these increases were linearly related to increased body mass in the tumour-bearing group so that the ratios of ventricular weights to body weight were similar in both groups. Furthermore, no pathologic changes such as myocardial fibrosis or asymmetric septal hypertrophy were present in the tumour-bearing rats. Thus, under the conditions of this study, growth hormone excess induced cardiac growth, which appeared to represent a manifestation of generalized body growth rather than a distinct pathologic process. PMID- 2931535 TI - [The kidney and disseminated intravascular coagulation]. PMID- 2931536 TI - [Fibrinolysis and disseminated intravascular coagulation]. PMID- 2931537 TI - [Important measurement of fluorescence intensity in the determination of lymphocyte subsets and the detection of large granular lymphocytes (LGL)]. PMID- 2931538 TI - [Diagnosis of left-ventricular hypertrophy: present-day status and tomorrow's prospects]. PMID- 2931539 TI - [Spasm of the right coronary artery after percutaneous coronary angioplasty, occurring beyond the sites of arterial dilatation]. PMID- 2931540 TI - [Dynamics of epidemiological situation and the results of the program of prevention of arterial hypertension at industrial plants]. PMID- 2931541 TI - [Effectiveness of roentgeno-endovascular dilatation in the treatment of renovascular hypertension]. AB - The techniques and methodology of roentgeno-endovascular dilatation, used as part of the treatment for renovascular hypertension in 50 patients with 66 arterial stenoses of varying etiology, are described. The factors that may affect the efficacy of the procedure are discussed: the duration and etiology of the disease, stenosis localization, the number of affected renal arteries, plasma renin activity in renal veins, the dilating catheter used, etc. The stenosed portion of an artery could not be passed in 4 patients. In 38 (82.6%) of 46 patients, whose stenosed renal arterial segments were successfully passed and roentgeno-endovascular dilatation was attempted, systemic arterial BP eventually returned to normal or diminished. PMID- 2931543 TI - [Intra-operative vasodilation in reconstructive surgery of combined arteriosclerotic lesions of arteries of the pelvis and lower limbs]. PMID- 2931542 TI - [Newly developed stenocardia: electrocardiographic and angiographic comparisons and the possibility of conducting intraluminal dilatation of coronary arteries]. AB - Fifty coronary patients were examined within the first 3 months after the onset of anginal attacks. All patients were subjected to coronaroangiographic investigation, bicycle ergometry, and 45 patients, to ECG-monitoring. Resting ECG patterns were assessed. One coronary vessel, the anterior interventricular branch of the left coronary artery in most (73%) cases, was affected in 66% of the patients. The stenoses suitable for intraluminal balloon dilatation were found in 58% of the patients with one vessel affected. In a considerable proportion (24%) of the patients, 2 or 3 arteries were affected. Combined electrocardiographic investigation demonstrated lesions of the anterior interventricular branch of the left coronary artery. The early results obtained with the intraluminal balloon dilatation of coronary arteries (16 attempts in 13 patients) showed good clinical effect to accompany anatomically-successful procedures (8 patients). PMID- 2931544 TI - [Elephantiasis of the anterior abdominal wall]. PMID- 2931545 TI - [A vascular bougie]. PMID- 2931546 TI - [Laparoscopy in the treatment of acute adhesive intestinal obstruction in children]. PMID- 2931547 TI - [Hypoplastic left heart syndrome--clinical and pathologico-anatomic findings]. AB - In twenty-two cases with hypoplastic left heart syndrome the anamnestic criterias and the clinical features were analysed. The pathologic specimens were examined in thirteen cases. The relations of the left heart to the right heart were measured. The same information is to be measured by two-dimensional echocardiography intra vitam. It should be discussed whether it is possible to perform an operative procedure in some rare cases of hypoplastic left heart syndrome. PMID- 2931548 TI - [1st postwar XIII All-Union Congress of Therapists (15-20 June 1947, Leningrad)]. PMID- 2931549 TI - [Leningrad therapists in World War II 1941-1945]. PMID- 2931550 TI - [Complications of drug therapy in patients with brucellosis]. PMID- 2931551 TI - Intestinal transport of vitamins. AB - Animals rely on acquiring through their diet, certain micronutrients required to support metabolism that we refer to as vitamins. The water-soluble vitamins are absorbed in the intestine only slowly by simple diffusion; specific mechanisms of transport have evolved that normally insure complete availability of each substrate to the organism. Secondary genetic errors that result in the impairment of an intestinal transport mechanism may become debilitating. PMID- 2931552 TI - Vitamins: an evolutionary perspective. AB - Access to vitamins and the genetic endownment to utilize them maintain vitamin dependent metabolic homeostasis in heterotrophs. Whereas the extent of adverse nutritional experiences has declined in modern human societies, phenocopies of deficiency diseases persist; accordingly, they have high heritability. The "vitamin-responsive hereditary metabolic diseases" identify DNA that specifies conserved apoenzyme domains interacting with coenzyme and the cellular processes providing access to coenzymes. Could heterozygosity at those loci also be a determinant of disease (or health) under certain circumstances? PMID- 2931553 TI - Successful nicotinamide treatment in an autosomal dominant behavioral and psychiatric disorder. PMID- 2931554 TI - A three-dimensional computational simulation of some sources of measurement artifact in microvascular pulsed ultrasound Doppler velocimetry. AB - Recent applications of 20 MHz pulsed ultrasound Doppler velocimetry (PUDVM) in microsurgical research have necessarily employed piezoelectric crystals whose diameter is not negligible compared to the lumen size (1-2 mm) of many vessels of interest. A three-dimensional numerical model was developed to explore relationships between actual and detected flow field parameters, for (steady) Poiseuille flow, when appreciable velocity gradients exist within the PUDVM sample volume. Validation studies showed that highly accurate velocity profiles could be obtained in the limiting case of a very small sample volume (0.1 mm radius), but that for currently employed crystals (approximately equal to 0.5 mm radius) there was appreciable underestimation of the centersteam velocity, and appreciable overestimation of the flow stream diameter. Errors in perceived velocity and flow rate were found to be relatively insensitive to perturbations in the sample volume thickness, in the size of the sampling range increment, or in the angle of insonation beam divergence. By contrast, these apparent flow parameters were found to be very sensitive to perturbations of sample volume diameter or of the Doppler angle. Small variations in the degree of partial sample volume overlap of the flowstream periphery were shown to be capable of causing large fluctuations in apparent flow stream diameter. PMID- 2931555 TI - Influence of the first formant on the recognition of voiced stop consonants by hearing-impaired listeners. AB - In order to examine first formant masking effects in hearing-impaired listeners, bay, day, and gay were synthesized with and without a first formant. The signals were presented at several levels. Removal of the first formant did not improve intelligibility at levels above, at, or below the point of maximum intelligibility. These results and others converge to suggest that masking spread from the first formant is not a significant factor in the identification of voiced stop consonants by listeners with sloping, mild-to-moderate hearing loss. PMID- 2931556 TI - A study of [3H]aldosterone binding by nuclear and cytoplasmic receptors of the rat kidney with different content of aldosterone in the organism. AB - The distribution of specific mineralocorticoid receptors in rat kidney cells was found to depend on aldosterone concentration. With increasing aldosterone concentrations the number of specific receptors for aldosterone in the cytoplasm decreased and their quantity in the nuclei increased. This was evidently due to their enhanced transport from the cytoplasm to the nuclei. It was found that aldosterone (its complex with the receptor) attached to non-histone proteins of chromatin and that the structural integrity of DNA is needed to provide the binding of this complex to the cell nuclei. The quantity of aldosterone acceptor sites in the kidney cell nuclei remained constant when aldosterone concentrations in the organism changed, and, hence, the functional states of the target organ changed too. PMID- 2931557 TI - B-lymphocyte associated differentiation antigen expression by 'non-B, non-T' acute lymphoblastic leukemia. AB - We investigated the neoplastic cells obtained from 37 cases of 'non-B, non-T' (SIg-E-) acute lymphoblastic leukemia (ALL) for their expression of 13 distinct monoclonal antibody defined B lymphocyte associated differentiation antigens. We correlated the expression of these B cell antigens with terminal deoxynucleotidyl transferase (TdT), HLA-DR antigen, common ALL antigen (cALLa), and cytoplasmic mu heavy chain (Cu) expression by these neoplastic cells. In this way, we were able to describe a hierarchy of B lymphocyte associated differentiation antigens as well as the marked phenotypic heterogeneity of 'non-B, non-T' ALL. TdT and HLA-DR are expressed throughout the stages of B cell differentiation represented by 'non B, non-T' ALL. The earliest B cell antigen appears to be Leu 12 (B4) followed by BA-2 and then BL2. OKB2, BL1 and BA-1 are acquired next, followed by B1, BL3, cALLa and Cu. BL7 appears just prior to SIg. OKB1, OKB4, OKB7 and BL4 appear at or after the time of SIg expression and hence are not expressed by 'non-B, non-T' ALL cells. This developmental hierarchy is supported by the results of phorbol ester (TPA) induction studies. Thus, cases of 'non-B, non-T' ALL constitute a useful model for probing the hierarchal expression of B cell antigens and delineating the B cell developmental pathway(s). PMID- 2931558 TI - Pulmonary endometriosis. PMID- 2931559 TI - Contractile and histochemical characteristics of the rabbit diaphragm in elastase induced emphysema. PMID- 2931561 TI - Detection of low-grade arterial stenosis using an automatic minimum-flow-velocity tracking system (MVTS) as an adjunct to pulsed ultrasonic Doppler vessel imaging. PMID- 2931560 TI - Magnesium regulation of the glycolytic pathway and the enzymes involved. AB - Past work, including our computer simulation of cardiac energy metabolism, indicates that magnesium is an important coherent controller of glycolysis and the Krebs cycle. Many of the glycolytic enzymes are sensitive to Mg2+. The most important effect is due to MgATP2-being a cofactor for a number of these enzymes while other chelation forms are inactive or inhibitory. The means by which Mg2+ and Mg2+ chelates of adenine nucleotides regulate the most important glycolytic enzymes--hexokinase, phosphofructokinase, aldolase, phosphoglycerate kinase, and pyruvate kinase--are described in detail. Creatine kinase, which is important in energy metabolism and highly sensitive to both metal ions and pH, is also discussed. It is necessary to properly control the composition of assay mixtures (particularly with regard to metal ions) in order to determine what actually regulates the activity of an enzyme. PMID- 2931562 TI - [Arnozan-Dubreuilh depilating folliculitis]. AB - Male patient, aged twenty-six years. Having an eight-and-a-half-year- old dermatosis of localized evolution on scalp, under arms, thighs, pubis and legs, characterized by inflammatory papules and follicular and extra-adnexial pustules, tiny scars and lack of hair in the affected areas. The authors present a representative case of "depilating folliculitis" of (Arnozan and Dubreuilh) stressing the following: Uncommon frequency in our country but frequent in warmer climates where it is observed mainly among peasants and sugar-cane workers. Wide depilated areas principally in folds. Seasonal outbreak. Good response to treatment. A revision of the theme is made emphasizing the histopathologic pathogenesis. PMID- 2931563 TI - [Peripheral blood lymphocyte populations in 2 cases of Behcet syndrome]. AB - The lymphocytes subsets in peripheral blood were studied in two patients with Behcet's syndrome. The finding about the decrease of T lymphocytes with the ratio elevated and specially the increase of B lymphocytes favors the hypothesis of predominance of the antibody formation over the cellular cytotoxicity. PMID- 2931564 TI - [Chronic endemic regional hydroarsenicism. The manifestations of arsenic poisoning caused by drinking water]. AB - This report deals with endemic chronic arsenical intoxication (HACRE) observed in several provinces in Argentina. Similar reports come from Chili, Mexico, Brasil, Bolivia, Peru and Japan. HACRE patients show no systemic, symptoms and specific manifestations are palmoplantar keratoderma, multiple cutaneous epitheliomas, mainly Bowen-type and respiratory or digestive carcinomas. The authors emphasize that these specific manifestations of HACRE are worth knowing for their possible social incidence. PMID- 2931565 TI - Binding of radioiodinated human beta-endorphin to serum proteins from rats and humans, determined by several methods. AB - Binding of immunoreactive radioiodinated human beta-endorphin (125I-beta-EP) to rat serum was demonstrated by gel filtration of 125I-beta-EP in pooled rat serum on Sephadex G-200. Two radioactive peaks associated with proteins eluted from the column. The first peak eluted at the void volume containing lipoproteins, alpha 2 and beta 2-macroglobulins, and the second peak at the fraction of albumin. Binding of 125I-beta-EP to albumin was directly proved by gel filtration of 125I beta-EP in buffer containing 4% human serum albumin on Sephadex G-200. Equilibrium dialysis was not applicable to investigating the interaction of 125I beta-EP with serum proteins, because of the intense nonspecific adsorption to the semipermeable membrane and the degradation of the peptide during dialysis. Therefore, in order to quantitatively evaluate the binding of 125I-beta-EP in sera from rats and humans, we utilized four other methods (ultrafiltration, charcoal adsorption, polyethylene glycol precipitation and equilibrium gel filtration). These methods corresponded well with each other and indicated 35-44% binding of 125I-beta-EP in rat serum. Binding of 125I-beta-EP in normal human serum was 36%, determined by ultrafiltration. Serum protein binding of 125I-beta EP was concentration independent over the concentration range studied (1-1000 nM). PMID- 2931566 TI - Effects of atrial natriuretic factor on human platelet function. AB - We examined the hypothesis that atrial natriuretic factor (ANF), a substance with known vasorelaxant activities, shares with other vasodilators the property of inhibiting platelet function. Aggregation of citrated platelet-rich plasma (PRP) from 23 healthy volunteers induced by ADP, adrenaline, arachidonic acid, collagen, gamma-thrombin, the endoperoxide analogue U-44069, serotonin, the calcium ionophore A-23187 or platelet aggregating factor was measured after incubation of PRP with ANF for 3 minutes at concentrations of 4 X 10(-9), 4 X 10( 8) and 4 X 10(-7) M or vehicle as control. ANF decreased ADP-induced aggregation significantly (P less than 0.02), but only at the highest concentration used and to a minor extent (control: 73.6 +/- 11.2%; after ANF 4 X 10(-7) M: 60.0 +/- 17.1%, mean +/- S.D., n = 39) by a selective inhibitory effect on the secondary wave; neither aggregation by all other agents tested nor thromboxane B2 generation induced by ADP and adrenaline was altered by incubation with ANF. Although ANF thus has detectable effects on ADP-induced platelet aggregation in vitro, these data suggest that ANF is unlikely to be a physiologically significant modulator of platelet function. PMID- 2931567 TI - Ionophoretic-like action of diflunisal. AB - It is shown that diflunisal, a derivative salicylic acid, causes uncoupling of oxidative phosphorylation owing to its property of carrying hydrogen ions through the inner mitochondrial membrane in such way that a short-circuit of protons is promoted. As a consequence of the above, the drug induces a decrease of the internal negative membrane potential and therefore the release of intramitochondrial calcium. In addition this report presents evidences that diflunisal behaves as a ionophore molecule since it induces cation extraction into an organic phase. PMID- 2931568 TI - Disability and driving in Switzerland. PMID- 2931569 TI - Platelet function tests: a critical review of methods. PMID- 2931570 TI - [Computational methods for determining the mean tissue doses during x-ray procedures]. AB - The Soviet and Finnish authors presented a short description of two computer methods to determine doses in the patients' organs. Based on the general principles, such as a semiempirical mathematical description of dose fields and a realistic anthropomorphous phantom, these methods differed significantly in the algorithms used and ways of solving specific problems. The comparison of these methods and calculated dose values with the results of experimental measurements on the phantom showed a good convergence of the results. The divergence of calculated and experimental data by the values of the mean absorbed doses in the organs did not exceed +/- 35%. The advantages and prospects of the use of the computer methods for the evaluation of doses received by patients, were demonstrated. PMID- 2931571 TI - [Economic efficacy of using computer technology for planning radiotherapy]. PMID- 2931572 TI - [Role of paramedical workers in providing complete dispensary care for the population]. PMID- 2931573 TI - [Organization of medical care for the victims in road traffic accidents]. PMID- 2931574 TI - Issues in the enumeration of handicapping conditions in the United States. PMID- 2931575 TI - Atlanto-axial instability in Down syndrome: a need for awareness. PMID- 2931576 TI - Are we stereotyping parents? A postscript to Blacher. PMID- 2931577 TI - Implantable infusion pumps: clinical applications. PMID- 2931578 TI - Microvascular adjustments during irreversible hemorrhagic shock in rat skeletal muscle. AB - A study was made of microvessel response to hemorrhagic hypotension and the subsequent restoration of blood volume. The experiments were conducted on anesthetized rats in which the cremaster muscle was exteriorized for intravital microscopy. Variables measured during hypotension (40 mm Hg for 60 min) and after blood restoration (120 min observation) included systemic blood pressure, heart rate, arteriolar and venular diameter, sensitivity to epinephrine, velocity and volumetric flow rate. These findings were correlated with 24-hr survival statistics. The response to hemorrhagic hypotension is a reflection of two separate adjustments, cardiac output and peripheral vascular behavior. In survivors, the microvascular sequelae following blood replacement was one of continuous improvement of muscle perfusion, whereas in nonsurvivors the picture was one of progressive deterioration. The consistent hallmark of irreversibility, arteriolar hyposensitivity, was associated with a continuous falling off in mean arterial pressure despite restoration of normal blood volume. PMID- 2931579 TI - Exercise-induced myocardial capillary growth in the spontaneously hypertensive rat. AB - Spontaneously hypertensive rats (SHR) were studied to test the hypothesis that endurance exercise training can stimulate capillary growth and offset the decrement associated with the development of myocardial hypertrophy. The exercise group (SHR-T) was trained on a treadmill for 10 weeks at 70-90% maximum VO2 and compared to nontrained SHR and normotensive Wistar-Kyoto (WKY) at 16 weeks of age. Thus, the training program coincided with the development of hypertension and hypertrophy in SHR. Image analysis was used to study capillaries in one micron thick left ventricular tissue samples from perfuse-fixed hearts. Training did not affect left ventricular mass or blood pressure, but reversed the characteristic decrements in capillary surface area (CSA), volume (CV), and numerical density (CD). CSA and CV were most markedly affected by exercise, as mean values for these parameters increased by 31 and 40%, respectively, compared to SHR. The magnitude of these changes approximated the magnitude of hypertrophy as evidenced by left ventricular weight/body weight ratios (42% in SHR and 37% in SHR-T). Anatomical intercapillary distance was also normalized by training (means +/- SEM): SHR-T, 11.65 +/- 0.31; SHR, 13.97 +/- 0.37; WKY, 11.19 +/- 0.37. These data indicate that exercise stimulates capillary growth in the face of developing hypertension and its related left ventricular hypertrophy. PMID- 2931580 TI - Reverse effect of gram-positive bacteria vs. gram-negative bacteria on adjuvant induced arthritis in germfree rats. AB - Germfree (GF) F344 rats developed severe adjuvant-induced arthritis with a 100% incidence after a single intradermal injection of heat-killed Mycobacterium bovis (BCG). Specific pathogene-free (SPF) rats developed less severe arthritis with a lower incidence. The rats colonized with Escherichia coli or Bacteroides developed mild disease comparable to that in SPF rats. The rats colonized with Bifidobacterium, Propionibacterium acnes, Lactobacillus casei, L. fermentum, L. murini, and L. acidophilus developed more severe disease than that in GF rats. Furthermore, the rats colonized with a mixture of E. coli and the above lactobacilli developed very mild disease similar to that in SPF rats. These results suggest that gram-negative bacteria, such as E. coli and Bacteroides, may suppress the disease, possibly through their lipopolysaccharides, and may be responsible for the lower susceptibility of SPF rats; gram-positive bacteria, such as Bifidobacterium, P. acnes, and lactobacilli, may enhance the disease, possibly through their peptidoglycans; and E. coli may play a dominant role in modulating the development of adjuvant-induced arthritis. PMID- 2931581 TI - Prenatal cytogenetic diagnosis. PMID- 2931583 TI - [A basic study on the anti-tumor activity of peripheral lymphocytes of tumor bearing rats by in vitro culture]. AB - In order to establish passive cancer immunotherapy by in vitro culture of lymphocytes, several methods were devised to induce and augment anti-tumor activity of peripheral blood lymphocytes (PBL) in the presence of interleukin-2 (IL-2). In vitro experiment: Weak anti-tumor activity appeared on culture of PBL in the presence of IL-2. On addition of MMC treated tumor antigen, the anti-tumor activity was augmented. Anti-tumor activity further increased on addition of peritoneal exudate macrophages or peripheral whole white blood cells containing monocytes to (2) as accessory cells. Effect similar to (3) was obtained in MLTC of peripheral whole white blood cells. [II] In Winn neutralization test, the strongest tumor-neutralizing activity was seen in the group of cultured lymphocytes with antigen and in the group of cultured leukocytes with antigen. This result agreed excellently with the results of the in vitro experiments [I]. [III] In the therapeutic experiment: Significantly better effect was noted in the treated group by cultured leukocytes with antigen than in the treated group by non-cultured lymphocytes. The treatment with 10(7) lymphocytes produced definitely prolonged survival of tumor-bearing rats compared to the treatment of 10(6) or less number lymphocytes. PMID- 2931582 TI - Gene organization and regulation in the qa (quinic acid) gene cluster of Neurospora crassa. PMID- 2931585 TI - [Congenital adrenogenital syndrome]. PMID- 2931584 TI - A series of repetitive DNA sequences are associated with human core and H1 histone genes. AB - Repetitive DNA sequences, derived from the human beta-globin gene cluster, were mapped within a series of human genomic DNA segments containing core (H2A, H2B, H3 and H4) and H1 histone genes. Cloned recombinant lambda CH4A phage with human histone gene inserts were analyzed by Southern blot analysis using the following 32P-labeled (nick translated) repetitive sequences as probes: Alu I, Kpn I and LTR-like. A cloned DNA designated RS002-5'C6 containing (i) a (TG)16 simple repeat, (ii) an (ATTTT)n repeat and (iii) a 52 base pair alternating purine and pyrimidine sequence was also used as a radiolabelled hybridization probe. Analysis of 12 recombinant phage, containing 6 arrangements of core histone genes, indicated the presence of Alu I, Kpn and RS002-5'C6 repetitive sequences. In contrast, analysis of 4 human genomic DNA segments, containing both core and H1 histone genes, indicated the presence of only Alu I family sequences. LTR-like sequences were not detected in association with any of the core or H1 histone genes examined. These results suggest that human histone and beta-globin genes share certain aspects of sequence organization in flanking regions despite marked differences in their overall structure and pattern of expression. PMID- 2931586 TI - [Pathogenesis of insulin-dependent (type I) diabetes mellitus]. PMID- 2931587 TI - The possible effect of high concentrations of propylene glycol on mitosis in human lymphocytes in vitro. AB - The effect of three concentrations, 1, 2 and 4 per cent, of propylene glycol has been investigated on human lymphocytes in vitro. An increased ratio of anaphase cells was observed at 4 per cent propylene glycol in the culture medium, when added for the last 24 h in 72 h blood cultures. No change in chromosome number has concomitantly been observed. A weak stathmokynetic action was induced by the same concentration of propylene glycol if administered for the final two hours of cell cultivation. These effects could be due to a delay in the normal sequence of the sister chromatid separation during mitosis, induced by the highest drug concentration. PMID- 2931588 TI - The effect of ethanol upon early development in mice and rats. VIII. Cytogenetic analysis of preimplantation stages of alcoholized mice. AB - Cytogenetic analysis was performed on preimplantation embryos (morulae and blastocysts) from control (untreated) and experimental groups of RAP strain female mice. The experimental groups underwent chronic alcoholization, acute ethanol intoxication of a combined treatment. The results suggest that the treatments applied did not induce, in our experimental conditions, chromosomal aberrations. PMID- 2931589 TI - Calcium cytochemistry and stereological morphometry of the intercalated ductal cells of the pancreas. AB - Using K-antimonate procedure, Ca2 binding sites in pancreatic small ductal cells were studied. Great precipitates were observed in the lumen of intercalated ducts, on luminal, contraluminal and lateral plasmalemma of centroacinar cells and in some of their organelles especially in mitochondrial matrix as well as on the euchromatin. Fine precipitates were present mainly on the endomembranes of perinuclear cisternae, endoplasmic reticulum, Golgi vesicles, mitochondria, secretory vesicles. Stereological studies showed in electron micrographs great differences from one cell type to another for the volume of mitochondria: 8% in acinar cell, 4.8% in centroacinar cell, 15.3% in small ductal cell and 4% in endocrine cell. The results strongly support the idea that centroacinar and intercalated ductal cells constitute the segments of pancreatic excretory cells, where the alkalinization of pancreatic juice takes place mainly by the secretion of bicarbonate and resorption of chloride ions. PMID- 2931590 TI - Sulphonated phthalocyanine induced caudal malformative syndrome in the chick embryo. AB - Sulphonated phthalocyanine (Pht.) has been tested for its possible noxious effect on the developing chick embryo. When injected into the subembryonic cavity of 40 45 hours incubated chick embryos (mainly 10-20 somite pairs), Pht. induces a highly reproducible caudal malformative syndrome (trunk and taillessness, various anomalies of the limbs). The main effect is--in about 15% of the malformed specimens--associated with unilateral microphthalmy and, less frequently, with coelosomy. Microscopically developmental disturbances of the caudal axial organs, of the mesonephros and of the limbs are observed. The initial pathological changes, at microscopic level, are necrosis and hemorrhages in the caudal axial and paraxial area. The allantois is poorly developed or even absent. Skeletal changes involve anomalies of the ribs and of the vertebral column and total or partial absence of the pelvic girdle bones. The high mortality, mainly during the first week, is due--first of all--to the developmental disturbances including the poor development or absence of the allantois. Control experiments with CuCl2 suggest the ethiological role of Cu. Pathogenetic aspects are discussed. PMID- 2931591 TI - The aberrant retroesophageal right subclavian artery. AB - Two cases with arteria lusoria were found at 278 routine dissections. These arteria arise as the last branches of the aortic arch and have a retroesophageal position. At the crossing point, the esophagus narrows due to the groove caused by the artery. The appearance of this malposition is the consequence of the perturbation in the organo-genesis of the right dorsal aorta and fourth branchial artery. The aberration can lead to disphagia lusoria. PMID- 2931592 TI - Rotavirus infection in gastroenteritis in children. AB - The electron microscopic investigation of biological materials (faeces, intestinal mucous biopsies) from 19 children and sucklings with clinically diagnosed acute gastroenteritis evidenced the presence of some rotavirus-like viral particles in 31 percent of cases. The age of hospitalized subjects varied between 4 months and three years. There have been identified viral particles in the cytoplasm of enterocytes of the intestinal villi and in suspensions of the fecal materials. PMID- 2931593 TI - A morphological quantitative study of small vessels in diabetic cardiomyopathy. AB - In 25 adult diabetic patients, tissue fragments from myocardium were removed at necropsy and processed routinely. The morphometrical analysis was made using eye piece ocular micrometer on a definite microscopic area. The arteriolar wall thickness increased from 5.10 mu +/- 1.71 in control group to 7.37 mu +/- 1.98 in the diabetic heart. The arterioles number decreased from 5.82/mm2 +/- 0.54 in the nondiabetics to 2.51/mm2 +/- 0.65 in the diabetic heart. The mean arteriolar diameter increased from 24.61 mu +/- 7.7 in the control group to 29.45 mu +/- 8.25 in the diabetic myocardium. The mean capillary diameter increased from 4.09 mu +/- 0.63 to 5.69 mu +/- 1.34 in diabetics. The capillaries number/mm2 decreased from 6.98 +/- 1.55 in the nondiabetics to 4.39 +/- 1.54 in diabetic patients. All differences, less the mean arteriolar diameter, are statistically significant. The following microscopical aspects were found in the small intramural coronary arteries: proliferation of endothelial cells with focal protuberances leading to partial narrowing of the lumen; increased thickness of the arteriolar wall due to fibrosis and accumulation of neutral mucopolysaccharides; alterations of elastic fibers. Frequently small areas of perivascular fibrosis and isolated foci of myocytolysis were found as well. These results suggest that the arteriolar impairment, especially the thickening of the arteriolar wall, could play a role in the pathogenesis of diabetic cardiomyopathy. PMID- 2931594 TI - Tubular carcinoma of the breast. AB - Forty-six tubular carcinomas selected from a series of 434 breast cancers, operated by radical mastectomy, were classified in four types: pure tubular carcinoma--one case, and three mixed types of tubular carcinoma in which the tubular structures decrease progressively in favour of a trabecular, poorly differentiated component. The tumors size and regional lymphatic dissemination increased in parallel with this dynamic change of parenchyma. Tubular carcinoma metastasized less frequently and in lower number of axillary lymph nodes as the other types of invasive breast tumors. PMID- 2931595 TI - Cytophotometric study of DNA content of cells in type III cervical smears. AB - Cytophotometric study of suspicious (group III of the Papanicolaou's classification) smears shows the heterogeneity of this group, which includes cases with diploid--tetraploid DNA modes, cases with a wide distribution of DNA values and aneuploid cases. The significance of these findings in relation with the biological properties of cells is briefly discussed. PMID- 2931596 TI - Sweat gland tumors with stromal haemangiomatous component: an undescribed type of skin tumors. Report of four cases. AB - An undescribed type of skin tumour, discovered in four cases, is reported. It is characterized by sweat-gland tumours (benign or malignant), with a common stromal haemangiomatous component which confers to it a peculiar pattern. Histogenetic possibilities are discussed. A collision mechanism between a pre-existent hamartomatous component (haemangioma) and a recent sweat-gland growth may be responsible for the appearance of this type and we think that this picture is more frequent but unidentified because, to our knowledge, it was not described up to the present paper. PMID- 2931597 TI - Penetration and proliferation of BHK and HeLa cells into a three-dimensional collagen matrix of bone stroma type. Preliminary results. AB - Some preliminary data regarding the test of penetration and proliferation of BHK and HeLa cells biocompatibility to a three dimensional stroma saturated with phosphorous and calcium salts (a biomaterial replacing bone) are presented. These data suggest that the analysed biomaterial might be used in surgical practices of prosthesis appliance on interfaces of fractured bone. PMID- 2931599 TI - [Application and considerations of intravenous psychosedation for aged dental patients with sick sinus syndrome]. PMID- 2931598 TI - Effect of nonspecific immune stimulation with BCG and polidin on the Ehrlich ascites tumor growth. AB - Investigations were performed to study: 1) the antitumor effect of BCG pretreatment on the development of Ehrlich ascites tumor in mice; 2) the effect of BCG administration in relation to the period of time before tumor inoculation and the dose levels used, and 3) the antitumor effect of an associated pretreatment of BCG and Polidin on the development of Ehrlich ascites tumor. BCG administered prior to Ehrlich ascites tumor inoculation have a protective effect evidenced by a delay in tumor development, a prolonged survival of the tumor host and, in some cases, even inhibition of tumor growth. The effect of BCG was highly dependent on 1) the dose and the time of administration of BCG and) 2 the combined pretreatment of BCG and Polidin. PMID- 2931600 TI - [Effect of lysophospholipid on Ca2-simulated adenosine triphosphatase in microsomal fraction of rat submandibular glands]. PMID- 2931601 TI - Type 2 fiber predominance in muscle cramp and exertional myalgia. AB - In patients complaining of muscle cramps and exertional myalgia, we found a significant decrease of type 1 muscle fiber proportion in comparison with a control group. The possible mechanism of this change is discussed. PMID- 2931602 TI - Isotretinoin for acne: the experience broadens. PMID- 2931603 TI - Changes in plasma lipids and lipoproteins during isotretinoin therapy for acne. AB - Abnormalities in plasma lipids are a recognized side effect of isotretinoin therapy for nodulocystic acne. We studied 60 patients during 20 weeks of isotretinoin therapy, to measure changes in plasma lipids and lipoproteins, to compare plasma lipid responses in men and women, and to determine whether there are alterations in levels of lipoprotein lipase or hepatic triglyceride lipase that could explain the development of isotretinoin-induced hypertriglyceridemia. Mean triglyceride levels rose in men and women, with maximum mean increases of 46.3 mg per deciliter (P less than 0.0001) and 52.3 mg per deciliter (P less than 0.002), respectively. The maximum level was reached by 4 weeks of therapy in men but not until the 12th week in women. Nine of 53 patients (17 per cent) completing 20 weeks of isotretinoin therapy acquired hypertriglyceridemia, with values of 200 to 600 mg per deciliter. Both men and women had significant increases in mean plasma levels of cholesterol and low-density-lipoprotein cholesterol and decreases in mean levels of high-density-lipoprotein cholesterol. There were no significant changes in mean levels of lipoprotein lipase or hepatic triglyceride lipase. Plasma lipid and lipoprotein levels returned to base line by eight weeks after discontinuation of the drug. If sustained over a long period, the change in the ratio of low-density-lipoprotein cholesterol to high-density lipoprotein cholesterol that we observed, from 2.4 to 3.0 (P less than 0.0001), would predict an increased risk of cardiovascular disease. PMID- 2931604 TI - The creatine kinase system in normal and diseased human myocardium. AB - We measured creatine kinase activity, isozyme composition, and total creatine content in biopsy samples of left ventricular myocardium from 34 adults in four groups: subjects with normal left ventricles, patients with left ventricular hypertrophy due to aortic stenosis, patients with coronary artery disease without left ventricular hypertrophy, and patients with coronary artery disease and left ventricular hypertrophy due to aortic stenosis. As compared with specimens of normal left ventricles, those from all patients with left ventricular hypertrophy had lower creatine kinase activity, higher MB creatine kinase isozyme content and activity, and lower creatine content. Specimens from the patients without left ventricular hypertrophy had normal creatine kinase activity, increased MB creatine kinase isozyme content and activity, and decreased total creatine content. The normal ventricles showed almost no MB isozyme content or activity. These data suggest that changes in the creatine kinase system occur in both pressure-overload hypertrophy and coronary artery disease. Patients with myocardial infarction who have mild or no preexisting fixed coronary artery disease or pressure-overload hypertrophy would not be expected to have elevation of serum MB creatine kinase. PMID- 2931605 TI - Onychomycosis due to saprophytic fungi. Report of 25 cases. AB - Twenty five cases of onychomycosis due to filamentous saprophytic agents were diagnosed within the period 1981-1982 in two mycology laboratories in Medellin, Colombia. These cases represented 4.5% and 9.5% respectively of the total fungal nail lesions (FNL) seen at those institutions. No explanation was found for the high frequencies, which sharply contrast with the previous local experience with the disease (0.4% of FNL). The responsible agents belonged to the following genera in decreasing order of frequency: Fusarium, Aspergillus, Scopulariopsis, Penicillium and Lasiodiplodia; two patients were infected with unidentified dematiaceous fungi and two more had the association of a saprophyte and a dermatophyte. In every case direct KOH preparations revealed septate hyphae, associated in 14 patients (56%) with chlamydoconidia. The only predisposing factors that were common to all these patients were age above 20 years and the use of footwear. PMID- 2931606 TI - Presynaptic serotonin receptor-mediated response in mice attenuated by antidepressant drugs and electroconvulsive shock. AB - Ligand-binding studies have demonstrated two types of serotonin (5-HT) receptor, 5-HT1 and 5-HT2, in the brains of rodents and there is additional evidence for the existence of 5-HT1 subtypes. Recently a new drug, 8-hydroxy-2-(di-N propylamino)tetralin (8-OH-DPAT), has been identified which shows high selectivity for binding to 5-HT1 (possibly 5-HT1A) receptors and which binds to presynaptic serotonin autoreceptors in some regions of rat brain. We have shown previously, that this compound produces a hypothermic response in mice, probably via an agonist action at serotonin presynaptic receptors. Here we show that a wide range of antidepressant treatments decrease the hypothermic response to 8-OH DPAT over a time course comparable to the onset of therapeutic action. Interestingly, repeated electroconvulsive shock (ECS) has the same effect. We propose that this change is relevant to the mechanism of action of antidepressant drugs. PMID- 2931608 TI - [A differentiated policy of vaccination against hepatitis B in an institute for the mentally retarded]. PMID- 2931607 TI - Analysis of the heart rate effects of 5-hydroxytryptamine in the cat; mediation of tachycardia by 5-HT1-like receptors. AB - The effects of 5-hydroxytryptamine (5-HT) on heart rate in anaesthetized cats were analysed both in intact animals and after spinal section plus vagotomy. The intact cat responded to 5-HT (3, 10 and 30 micrograms X kg-1, i.v.) with a brief, but intense, bradycardia and a longer-lasting hypotension. Administration of MDL 72222, a selective antagonist of M-type 5-HT receptors, blocked bradycardia elicited by 5-HT without affecting that caused by stimulation of the vagus nerve. In spinal cats the same doses of 5-HT increased heart rate and blood pressure. These effects remained essentially unchanged after bilateral adrenalectomy, guanethidine, propranolol and burimamide, suggesting that 5-HT acted directly on the myocardium and blood vessels. The tachycardic responses to 5-HT in spinal cats were little affected by 0.5 mg X kg-1 doses of MDL 72222 or of the 5-HT2 receptor antagonists, ketanserin, ritanserin or cyproheptadine. In contrast, the non-selective 5-HT receptor antagonist, methysergide, which binds to both 5-HT1 and 5-HT2 recognition sites in rat brain membranes, potently antagonized the 5-HT induced tachycardia in doses of 0.05 to 0.5 mg X kg-1. However pizotifen and mianserin, two other 5-HT2 antagonists which show poor affinity for 5-HT1 recognition sites, were also effective against the tachycardic response to 5-HT in doses of 0.5-4.5 mg X kg-1. The pressor responses to 5-HT in the spinal cat were markedly inhibited by all six 5-HT2 antagonists at a dose of 0.5 mg X kg 1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2931609 TI - [The Burma-Thailand railroad. Why the Burma-Thailand railroad had to be built]. PMID- 2931610 TI - Renovascular hypertension in a child: percutaneous transluminal renal artery angioplasty. PMID- 2931611 TI - Defective radioresistant suppressor cell activity in hemodialysis patients. AB - The immunologic alterations in patients on hemodialysis are only partially understood. We studied the Concanavalin A (Con A) induced suppressor cell activity of irradiated and nonirradiated cells in a mixed lymphocyte culture. Peripheral blood lymphocytes from 18 normal individuals and 14 patients on regular hemodialysis were incubated with two different concentrations of Con A (10 micrograms and 40 micrograms of Con A/million cells). Irradiated and nonirradiated cells were then tested for their capacity to suppress a standard MLC. The proliferative response to phytohemagglutinin, pokeweed mitogen and Con A was also determined. Suppressor cell activity of nonirradiated cells in hemodialysis patients was similar to that of controls, at both concentrations of Con A, while irradiated cells of hemodialysis patients showed a suppressor cell activity significantly lower than that of the controls, at a Con A concentration of 40 micrograms/10(6) cells (25.78 +/- 18.86% vs. 46.05 +/- 9.79%, p less than 0.001). The proliferative response of lymphocytes from hemodialysis patients to the three mitogens, did not show any difference when compared with normal controls. The normal proliferative response of lymphocytes from hemodialysis patients to mitogens and the normal suppressor cell activity of nonirradiated cells, suggest a normal T cell function. The abnormal suppressor cell activity in irradiated cells indicate that the radioresistant population has a functional defect. The cell responsible for this suppressor defect probably belongs to the monocyte/macrophage population because of its relative radioresistance. PMID- 2931612 TI - In vivo and in vitro effects of bradykinin on the release of beta-endorphin-like immunoreactivity. AB - The effect of bradykinin (BK) on the release of beta-endorphin-like immunoreactivity (beta-EpLI) in rats was studied in vivo and in vitro. Intraperitoneal injection of BK at 5 micrograms/100 g body weight resulted in significant increase in the plasma beta-EpLI level after 15 min. BK at concentrations of 10(-12)-10(-7) M also caused dose-dependent stimulation of beta EpLI release from dispersed cells of rat anterior pituitary. On gel chromatography, the beta-EpLI released by incubation of the cells with 10(-7) M BK separated into two components, eluted in the same positions as human beta lipotropin and human beta-endorphin, respectively. BK did not stimulate beta-EpLI release in Ca++-free medium. Addition of 10(-3) M verapamil or 10(-6) M dexamethasone to the incubation medium inhibited BK-induced beta-EpLI release from the cells. Quabain (10(-5) M) also stimulated beta-EpLI release, but its effect was not additive with that of BK. These results indicate that BK stimulates beta-EpLI release and that calcium ion is involved in the mechanism of this effect. PMID- 2931613 TI - Pharmacological studies on the serotoninergic and nonserotonin-mediated stimulation of prolactin and corticosterone secretion by fenfluramine. Effects of pretreatment with fluoxetine, indalpine, PCPA, and L-tryptophan. AB - Administration of the serotonin-releasing drug fenfluramine to male rats caused a dose-dependent increase in both plasma prolactin and corticosterone levels. The effect of fenfluramine on prolactin was maximal at 30 min after injection, whereas the effect on plasma corticosterone levels reached a maximum 2 h after injection. In order to determine if the effect of fenfluramine on both hormones was mediated via serotonin release, rats were pretreated with the serotonin uptake inhibitors fluoxetine (10 mg/kg i.p.) or indalpine (10 mg/kg i.p.) 30 min prior to administration of fenfluramine (5 mg/kg i.p.). Both fluoxetine and indalpine inhibited the effect of fenfluramine on plasma prolactin levels, but did not modify the effect of fenfluramine on plasma corticosterone levels. Pretreatment of rats with the serotonin precursor L-tryptophan (100 mg/kg i.p.) potentiated the effect of a submaximal dose of fenfluramine (2 mg/kg i.p.) on plasma prolactin levels, but did not affect the corticosterone response. Depletion of serotonin stores by pretreatment with the serotonin inhibitor p chlorophenylalanine (300 mg/kg i.p.; 72 h) did not significantly prevent the effect of fenfluramine on either hormone. There was a 34% inhibition of the effect of fenfluramine on plasma prolactin levels, but this effect was not statistically significant. The results of the experiments suggest that the effect of fenfluramine on prolactin secretion is mediated, at least in part, by a serotoninergic mechanism, but the effect on corticosterone secretion is not mediated via serotonin release. PMID- 2931615 TI - Beta-endorphin suppression of acute morphine abstinence in morphine dependent monkeys: effective given intraventricularly but ineffective given intravenously. AB - Six female adult Macaca mulatta monkeys were made dependent upon morphine sulfate and were implanted with a chronic indwelling needle in the lateral ventricle of the brain for sterile intraventricular injections. Both beta-endorphin and morphine, in a dose dependent manner given intraventricularly suppressed the signs of 14 hour acute morphine abstinence. On a molar basis, beta-endorphin was more active than morphine in suppressing the signs of morphine abstinence. When given intravenously in much larger doses, beta-endorphin was ineffective in contrast to morphine which was effective in suppressing abstinence. PMID- 2931614 TI - Effects of intrahypothalamic injection of quinolinic acid on anterior pituitary hormone secretion in the unanesthetized rat. AB - Bilateral intrahypothalamic injections of the brain metabolite quinolinic acid (QUIN) were made in an attempt to examine its effects on the secretion of LH, PRL, GH and TSH. Quin, a neuroexcitatory amino acid with close structural similarities to glutamate, kainate and N-methylaspartate, was infused into unanesthetized male rats, the animals sacrificed 7.5 min later, and serum hormone concentrations determined by radioimmunoassay. QUIN caused surges in LH, PRL and GH release (316, 607 and 1,134% of control, respectively, at 50 micrograms QUIN) without affecting the serum concentrations of TSH. At lower doses, a preferential effect of QUIN on PRL release was observed. All QUIN-induced hormonal changes were inhibited by concomitant administration of the specific antagonist (-)-2 amino-7-phosphonoheptanoic acid, indicating the presence of QUIN-sensitive receptors on neurons which are intimately associated with endocrine regulation. Moreover, because QUIN-treated animals exhibited behavioral signs of seizure activity and neuroendocrine dysfunction has been reported to occur in human convulsive disorders, the data are also of interest in view of a possible mechanistic link between epileptic phenomena and hormone secretion. PMID- 2931616 TI - Long-term haloperidol treatment elevates beta-endorphin levels in the intermediate pituitary but not in rat brain. AB - Long-term treatment of rats with haloperidol, a dopamine receptor antagonist, produced a dose-dependent increase in immunoreactive beta-endorphin (i beta-END) concentrations in the neurointermediate lobe of the pituitary (NIL). In contrast, chronic haloperidol treatment had no significant effect on i beta-END levels in the hypothalamus, the midbrain or in discrete, microdissected brain nuclei even when administered at a dose (5 mg/kg) ten-fold higher than that which elevated i beta-END levels in the NIL. Chronic treatment with bromocriptine, a dopamine receptor agonist, had the opposite effect on the NIL, lowering i beta-END levels to approximately one-third of control values, but it did not affect hypothalamic i beta-END concentrations. These data are consistent with prior evidence that the synthesis of beta-END by IL melanotrophs is reciprocally modulated by dopaminergic ligands. The results indicate, however, that beta-END-releasing neurons are not similarly regulated. PMID- 2931618 TI - [Effect of manganese chloride poisoning during pregnancy and lactation on the levels and synthesis of gamma-aminobutyric acid (GABA) in the rat brain]. PMID- 2931617 TI - Left carotido-cavernous fistula with right exophthalmos: treatment by detachable balloon. Case report and literature review. AB - A case of left carotidocavernous fistula with right exophthalmos is reported. It is the thirteenth reported case in the literature since 1907. Mechanism of the exclusively contralateral exophthalmos is discussed. Temporary venous thrombosis of the ipsilateral ophthalmic vein and inferior petrosal sinus is likely. Successful treatment by detachable balloon with occlusion of the carotid siphon is described. PMID- 2931619 TI - [A case of malignant hypercalcemia treated with mitramycin]. PMID- 2931620 TI - Abdominal wall metastases seven years after resection for carcinoma of the appendix. PMID- 2931621 TI - Antidipsogenic action of alpha-human atrial natriuretic polypeptide administered intracerebroventricularly in rats. AB - Intracerebroventricular (i.c.v.) administration of alpha-human atrial natriuretic polypeptide (alpha-hANP) in a dose of 5 micrograms did not change water intake in normal rats, while 0.1 micrograms of angiotensin II (AII) and 0.5 micrograms of carbachol caused a marked increase in water intake for 30 min after i.c.v. injections. The water intake induced by 0.1 micrograms of AII was significantly suppressed by the simultaneous administration of 2 and 5 micrograms of alpha hANP. However, alpha-hANP did not affect the water intake caused by 0.5 micrograms of carbachol. In 24-h water-deprived rats, alpha-hANP in doses of 2 and 5 micrograms pronouncedly inhibited the water intake. alpha-hANP did not change the food intake in 24-h fasted rats nor the locomotor activity in normal rats. These findings suggest that alpha-hANP in the central nervous system may play an important role in controlling drinking behavior, interacting with AII. PMID- 2931622 TI - Presence of immunoreactive alpha-melanotropin and beta-endorphin in spinal motoneurones of the dystrophic mouse. AB - Two derivatives of the stem hormone opiomelanocortin, alpha-melanotropin (alpha MSH) and beta-endorphin, were detected immunocytochemically in the cell bodies and in the peripheral axon terminals of spinal motoneurones in immature but not in adult healthy mice. Immunoreactivity was demonstrated in motoneurones in both immature and adult mice with inherited muscular dystrophy. These results provide evidence for a motoneurone abnormality in murine dystrophy. The observations are discussed in the light of trophic influences over neuromuscular transmission which have been attributed to this family of neuropeptides. PMID- 2931623 TI - Two types of cat static fusimotor neurones under separate central control? AB - The effect on the fusimotor system of an injection of the gamma-aminobutyric acid (GABA) antagonist picrotoxin into the reticular part of the substantia nigra (SNR) was studied in muscle spindle primary and secondary endings of pretibial flexors in cats anaesthetized with ketamine. Changes in fusimotor action after drug administration were deduced from changes in bias and sensitivity to sinusoidal stretching of the receptor-bearing muscles when compared to the deefferented preparation. Intranigral injection of picrotoxin (2 micrograms) removed a tonic static fusimotor action from flexor muscle spindle primary endings without affecting the secondary endings in the same muscles. It is concluded that static gamma motoneurones of cat flexors are of more than one functional type, and that the central nervous control of the static fusimotor input to cat flexor muscle spindles has selective access to static bag2 fibres and nuclear chain fibres. PMID- 2931624 TI - [3H]Spiperone binding in the rat striatum during the development of physical dependence on phencyclidine and after withdrawal. AB - Binding of [3H]spiperone to dopamine D2 receptors was measured in the striatum of male rats that were infused with phencyclidine (PCP, 45 mg/kg per day) or vehicle (saline) via an intrajugular cannula for 1, 3.5, or 7 days. The 7-day PCP infusion, which was shown previously to induce physical dependence, produced a significant 30% decrease in receptor density (Bmax). Two days after termination of the 7-day PCP infusion, Bmax values were no longer significantly lower than those of saline-infused controls. The acute administration of PCP (20 mg/kg, i.p.) did not alter receptor density 45 min later. PMID- 2931625 TI - Muscarine-binding sites localized to cortical dopamine terminals. AB - The effects of lesions to the mesocortical dopaminergic system on D2 dopamine receptors and muscarine receptors in the frontal cortex of the rat was examined. Four weeks following 6-hydroxydopamine lesioning of the ventral tegmental area, there was a 26% increase in the number of [3H]spiroperidol sites, and a 13% decrease in the number of [3H]oxotremorine-M sites in the frontal cortex, indicating a development of D2 receptor supersensitivity, as a result of deafferentation, and a loss of acetylcholine sites, as result of terminal degeneration. This demonstrates that in the frontal cortex, as in the striatum and nucleus accumbens, the activity of dopaminergic terminals may be partially modulated by cholinergic inputs. PMID- 2931626 TI - Effects of branched-chain amino acids on beta-endorphin in the pituitary of the rat. AB - Despite evidence that the branched-chain amino acids (BCAAs) influence brain metabolism and neurotransmitter synthesis, there is little information on the neuroendocrine effects of the BCAAs. We now report that administration of a mixture of the BCAAs 3 times daily for 12 days to Sprague-Dawley rats decreased the concentration of beta-endorphin immunoreactivity (BEI) in the neurointermediate lobe of the pituitary. In BCAA-treated rats, BEI was 21 +/- 4 compared to control levels of 57 +/- 12 (ng/microgram of protein). The BCAAs had no effect on the level of BEI in the adenohypophysis. These findings suggest that changes in availability of leucine, isoleucine, and valine mediate specific neuroendocrine responses to metabolic perturbations in the rat. PMID- 2931627 TI - Regional distribution of [3H]nitrendipine binding in human brain. AB - Evidence for the binding of a calcium antagonist, [3H]nitrendipine, to human brain membranes was obtained. This binding was saturable, specific and of high affinity with a dissociation constant (Kd) of 0.62 nM in the prefrontal cortex and 0.82 nM in the caudate. The maximal numbers of binding sites (Bmax) in these areas were 57.5 and 32.3 fmol/mg protein, respectively. [3H]Nitrendipine binding to membranes from 27 regions in the post-mortem human brains was measured. The highest levels of 0.5 nM [3H]nitrendipine binding were seen in the cerebral cortex, amygdala and thalamus, and levels in the midbrain, cerebellum and pallidum were considerably lower. PMID- 2931628 TI - Autoradiographic studies on dopamine D2 receptors in rat pituitary: influence of hormonal states. AB - The influence of the estrous cycle on the density of dopamine D2 sites in the rat pituitary was studied by quantitative autoradiography using [3H]spiperone. While no significant changes were found in the neural and intermediate lobes during the cycle, a lower number of D2 receptors in the anterior lobe was observed in the proestrus when compared to the diestrus. The difference in the density of [3H]spiperone binding in the pituitary between male and female rats was also analysed. A significantly lower number of receptors in the three lobes of the male pituitary, as compared to those of the female, was found. Finally, no significant variation in the number of binding sites in the 3 pituitary lobes was observed between lactating and separated mothers. PMID- 2931629 TI - Dopaminergic agents differentially alter beta-endorphin processing patterns in the rat pituitary neurointermediate lobe. AB - We have established the content and molecular species of immunoreactive beta endorphin (ir-beta-END) and immunoreactive N-acetyl-endorphin (ir-Nac-END) in rat neurointermediate lobe by specific radioimmunoassay (RIA) and high-performance liquid chromatography after chronic administration of dopamine (DA) agonists and antagonists. The DA agonist, bromocriptine, reduces tissue levels of all major immunoreactive species, in particular the C-terminally shortened N-acetylated forms. The DA antagonist, haloperidol, proportionally increases all immunoreactive forms, except Nac-beta-END, thus altering the relative abundance of this species. These data indicate that DA is involved in the control of both tissue levels and processing of beta-END-like peptides in the rat neurointermediate lobe. PMID- 2931630 TI - Topography of nicotinamide adenine dinucleotide phosphate-diaphorase staining neurons in rat striatum. AB - A new modification of the nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase reaction was used to study the distribution of a specific subset of neurons in rat striatum. These neurons are known to also contain somatostatin like immunoreactivity (SLI). We have previously found a heterogeneous distribution of SLI in rat striatum. In the present study, we found NADPH diaphorase neurons to be evenly distributed throughout the striatum and nucleus accumbens. There was no increase in the number of NADPH-diaphorase neurons in ventromedial striatum or nucleus accumbens where concentrations of SLI are highest. This suggests that there may be somatostatin afferents to ventromedial striatum and nucleus accumbens. In addition, the NADPH-diaphorase reaction was stable for up to 24 h in an animal model stimulating human autopsy conditions. PMID- 2931631 TI - Change in content, incorporation and lipoxygenation of docosahexaenoic acid in retina and retinal pigment epithelium in canine ceroid lipofuscinosis. AB - We have examined the metabolism of docosahexaenoic acid (22:6, n-3) in retina and retinal pigment epithelium of normal dogs and those affected with canine ceroid lipofuscinosis (CCL), a hereditary degenerative neurological disorder. In the CCL retina, there was a decrease in 22:6 content in phospholipids, particularly phosphatidylethanolamine. This decrease in 22:6 was compensated by an increase in arachidonic acid (20:4, n-6). In contrast, CCL retinal pigment epithelium had higher levels of 22:6 and lower levels of 20:4 in phosphatidylethanolamine. The in vitro incorporation of radiolabeled 22:6 into glycerolipids of CCL retina and retinal pigment epithelium was increased as compared to control. The major lipoxygenase reaction product of 22:6, (11-hydroxy-4,7,9(trans)13,16,19)-22:6, increased 31% in CCL retina, but not in the retinal pigment epithelium. This is the first report describing alterations in content, incorporation and lipoxygenation of 22:6 in an animal model of a human disease (Batten's disease). PMID- 2931632 TI - Chiropractic and acute low back pain. PMID- 2931633 TI - So you haven't taken the Heptavax-B vaccine??? PMID- 2931634 TI - A dental health perspective: the consequences of an aging population. PMID- 2931635 TI - Sonographic imaging of intrauterine adhesions. AB - Hysterosalpingography and hysteroscopy are the diagnostic modalities most commonly used to evaluate and follow intrauterine adhesions (Asherman syndrome). Three patients with intrauterine adhesions are presented. These adhesions were visualized with sonography and appeared as dense intrauterine lines. These lines disappeared after hysteroscopic lysis of the adhesions. The present results indicate that sonography may alert the clinician to the presence of intrauterine adhesions. PMID- 2931636 TI - Simple solution--sometimes. PMID- 2931637 TI - [Yersinia enterocolitica and Campylobacter jejuni in their significance for milk hygiene]. PMID- 2931638 TI - [Analgesics consumption and analgesic-induced nephropathies in West Germany]. PMID- 2931639 TI - [The significance of standardized psychodiagnostic methods for the forensic psychiatric expert evaluation of primary intelligence disorders]. PMID- 2931640 TI - [Hypertension in eastern Sierra Leone]. PMID- 2931641 TI - [Health-related interests of student teachers--an empirical pilot study in an educational college]. PMID- 2931642 TI - [Infection prevention from a legal viewpoint]. PMID- 2931643 TI - [Mental patients in homes for the aged--wrong placement, needs and care structure]. PMID- 2931644 TI - [Hepatitis B infection in prostitutes]. PMID- 2931645 TI - [Occupational political status in the public health service]. PMID- 2931646 TI - [Violence against children and the public health service]. PMID- 2931647 TI - [Epileptic attacks in childhood--myopathies in childhood]. PMID- 2931648 TI - [Quality of environmental air]. PMID- 2931649 TI - [Air quality of indoor rooms]. PMID- 2931650 TI - [Collapse therapy and other historical therapeutic methods in tuberculosis]. PMID- 2931652 TI - [Public health technical monitoring of kindergartens and schools]. PMID- 2931651 TI - [What do you actually do for your health?]. PMID- 2931653 TI - [Diseases of the heart and cardiovascular system]. PMID- 2931654 TI - [Drinking water pollutants--their monitoring and elimination exemplified by lead and halogenated hydrocarbons]. PMID- 2931655 TI - [Reform of Penal Code Paragraph 218 and its consequences from the viewpoint of the Department of Public Health]. PMID- 2931656 TI - [Integrated psychosomatic inpatient rehabilitation]. PMID- 2931657 TI - Fracture of heterotopic ossification of the abdominal wall. A case report. PMID- 2931658 TI - [Reaction of the posterior corneal epithelium to aqueous humor substitutes]. PMID- 2931659 TI - [Lecturing students on topics in ophthalmology]. PMID- 2931660 TI - [Successful surgical management of coronary rupture occurring during angioplasty]. PMID- 2931661 TI - [Nasal rhinophyma. Combined surgical treatment and cryotherapy]. PMID- 2931663 TI - [Wild ungulates as a food source for ixodid ticks in Belorussia]. AB - The stock rise of elk, roe and boar up to 24.2, 20.8, and 29.3 thousand heads, respectively, increased their role as hosts of imaginal developmental stages of Ixodes ricinus and Dermacentor pictus. Elk plays an especially important role as the host of I. ricinus (the index of ticks abundance--7.31, the index of saturation--176.9). The indices of saturation of I. ricinus imagos on roe and boar are 96.5 and 73.1, respectively. D. pictus imagos parasitise, in general, board (the index of ticks abundance--3.06, the index of saturation--81.7). The role of ruminants as hosts of I. ricinus larvae and nimphs is relatively small. Larvae and nimphs of D. pictus do not occur on ruminants. PMID- 2931662 TI - The assessment of pain and plasma beta-endorphin immunoactivity in burned children. AB - The need for better analgesia during burn dressing changes (BDCs) in acutely burned children led us to assess pain during BDC with a large 0-10 thermometer like scale which was well accepted and appeared to reflect the varying degrees of pain that patients experienced. Pain scores were obtained at least once each minute throughout 33 BDCs in 15 patients of 8-17 years. Plasma levels of beta endorphin immunoactivity (iB-EP) were measured at 5 intervals before and after BDC; mean values (+/- S.E.M.) ranged from 30.5 +/- 4.63 pg/ml (before BDC and analgesic) to 19.2 +/- 3.02 pg/ml (immediately following BDC). The mean pain score (MPS) for each BDC was inversely related to the iB-EP levels of that day (P less than 0.001 with 4 of the 5 iB-EP determinations). The MPS varied directly with the extent of burn injury and inversely with weight; the 2 variables together predicted MPS as well as the iB-EP alone (r2 = 43 and 36% respectively). PMID- 2931665 TI - [New species of Ostertagia sogdiana sp. n. (Nematoda, Trichostrongylidae) from the domestic goat in Uzbekistan]. AB - In the abomasum of domestic goat of Uzbecistan there were found ostertagiae which differ distinctly from earlier described species of the family Trichostrongylidae in size and structure of spicules and in the morphology of genital conus. The new species Ostertagia sogdiana sp. n. (fam. Trichostrongylidae) is described. PMID- 2931664 TI - [Find of coccidians of the genus Isospora (Coccidiida) in the Central Asian jackal]. AB - During the period of 1981-1982 9 central asiatic jackals were caught in the Chimkent region and "Kent-Bulak" area on the left bank of the Syr-Darja of the Kzyl-Orda region. In two jackals caught in the Kzyl-Orda region one species of coccidians of the genus Isospors was found. Oocysts of I. kzilordiniensis are oval without micropyle, the membrane is monolayer, smooth, greenish, 1.5 mu thick. The size of oocysts is 26.1-31.9 X 17.4-20.3. PMID- 2931666 TI - Lack of suppression by concanavalin A-activated neonatal mononuclear cells. AB - We studied the mixed leukocyte culture suppression generated by cord and newborn mononuclear cells stimulated by concanavalin A (Con A) compared to normal adult cells and cells from patients with systemic lupus erythematosus. Also we studied the effect of supernatants from cord or adult cells stimulated with Con A linked to sepharose (Con A sepharose). Peripheral blood mononuclear cells from 15 adults, 10 normal newborns, 23 cord blood samples, and 11 patients with systemic lupus erythematosus were preincubated with Con A for 48 hr, irradiated, and added to a one-way mixed leukocyte culture. Adult Con A-activated cells suppressed the mixed leukocyte culture by 30 +/- 6.5%. By contrast cord cells and newborn cells had no suppressive activity; these cells resulted in stimulation of 18 +/- 12.1 and 18 +/- 7%, respectively. This lack of suppression also was present in systemic lupus erythematosus cells (11.2 +/- 13.3). The supernatants of both Con A sepharose-stimulated cord and adult cells showed significant suppressive activity and there was some suppressive activity of sepharose-stimulated cells alone. These results suggest that the mixed leukocyte cultures suppressive activity observed previously by newborn cells is radiosensitive and dependent on ongoing cell division for its expression. It also is independent of prior mitogenic stimulation. PMID- 2931667 TI - American Academy of Pediatrics. School-aged children with motor disabilities. Committee on children with disabilities. PMID- 2931668 TI - Infant rash caused by paracetamol in breast milk? PMID- 2931669 TI - [Mitral valve prolapse in school children living in the central mountainous regions of Kirghizia]. PMID- 2931670 TI - [Re the lecture by M.P. Matveev, Z.I. Vikharevii, S.V. Levitskii, R.A. Tiurkian: "Our views on sepsis"]. PMID- 2931671 TI - [25th anniversary of the Scientific-Research Institute of Pediatrics of the Ministry of Health of the Georgian SSR]. PMID- 2931672 TI - [Pharmacological prevention of exercise-induced bronchospasm in patients with asthma]. PMID- 2931673 TI - [Effect of Berodual on spirometric indicators in patients with reversible bronchial stenosis]. PMID- 2931674 TI - [Systemic lupus erythematosus (problems of diagnosis and treatment)]. PMID- 2931675 TI - Causal links between plasma and CSF endorphin levels in stress: vector-ARMA analysis. AB - To explore causal links between vital sign responses and immunoreactive beta endorphin ("i-BE") rises in blood and CSF during ovine endotoxin stress, we analyzed concurrent i-BE levels in these two compartments by a "vector-ARMA" (= autoregressive moving average) method. This technique--widely used for modeling in other applications--has not to our knowledge been employed to study dynamic relationships of neuropeptides. Log-transformed i-BE levels were first "filtered" by repeated observations ANOVA to confirm significance of rises in both compartments. Next, vector-ARMA methodology was applied to derive an optimal causal model of vital sign changes and i-BE entry into plasma vs. CSF pools. The model indicated that reflux of i-BE from blood into CSF contributed to increases in CSF levels of this hormone. This novel application to neuroendocrinology of this approach illustrates its utility in evaluating changes in one or more neuropeptide levels in multiple compartments to indicate potentially causal relationships. PMID- 2931676 TI - A possible prenatal evaluation of renal function by amino acid analysis on fetal urine. AB - Intrauterine treatment of 4 fetuses with urethral obstruction was attempted in the third trimester of pregnancy. The fetuses displayed varying sonographic findings including pyelectasis, caliectasis, hydroureter, bladder dilatation, ascites, hydrops, missing kidneys and oligohydramnios. Ultrasonically guided aspiration from the dilated structures was carried out to relieve pressure on the kidney parenchyme and to collect fluid samples for diagnostic purposes. Amino acid concentrations in the fetal urine showed a pattern similar to plasma in 2 fetuses, a pattern almost like urine in 1 fetus and an intermediate pattern in the 4th fetus. Only the fetus with normal amino acid concentrations in the urine survived: the other 3 died in uremia shortly after birth. In 3 cases cells from the aspirated urine were cultured and used for chromosome analysis. The cell cultures grew fast and karyotyping was possible within 1 week. In 2 fetuses an intrauterine catheter was inserted to drain the kidney permanently into the amniotic cavity. In the first case the catheter was displaced to the fetal abdomen after some days of successful drainage. In the second case the catheter tore the placenta, and the child had to be delivered immediately. PMID- 2931677 TI - High resolution chromosomes from first trimester trophoblast cultures. AB - A simple method for obtaining prometaphase chromosomes from cultured first trimester cells involves the addition of BrdU and FdU 11 h before harvest and ethidium bromide 1.5 h before harvest. High resolution R-banding is obtained by acridine orange staining. PMID- 2931678 TI - Prenatal diagnosis of trisomy 21 and X/XX sex chromosome mosaicism. AB - Double aneuploidy involving Down syndrome and Turner syndrome is a rare chromosomal abnormality presumed to occur with a frequency of about 1 in 2 million births. Twenty-one cases of this combined anomaly have been reported and two infants were born with this anomaly after a mistake in prenatal diagnosis. We report the first prenatal diagnosis of Down syndrome combined with Turner mosaicism and suggest that this polysyndrome may be more common than previously estimated. We, therefore, wish to alert cytogenetic laboratories performing prenatal diagnoses of the potential risks of misdiagnosis of this polysyndrome if banding is not performed and if a sufficient number of mitotic cells are not analysed. PMID- 2931679 TI - [Anti-centromere antibody, biological marker of the CREST syndrome as distinct from scleroderma]. AB - Using HEp2 cells to study antinuclear antibodies has resulted in the discovery of the anti-centromere antibody which is thought to separate the CREST syndrome from progressive systemic sclerosis (scleroderma). This antibody seems to be exceptional in healthy subjects and are in patients with connective tissue diseases, except for scleroderma. It has also been found in CREST syndrome associated with other diseases, such as primary cirrhosis and neoplasias. In our study, the sensitivity of the anti-centromere antibody was 89.1% and its specificity 92.3% which shows that it is worth looking for. PMID- 2931680 TI - [Percutaneous cholecystostomy in so-called post-stress acute cholecystitis]. AB - During the last 8 years 51 cases of acute post-traumatic or post-operative cholecystitis were observed in our intensive care unit. Twelve patients benefited from ultrasonically guided percutaneous cholecystostomy under television control. Diagnosis was made by ultrasonic examination and was based on the finding of an enlarged and tender gallbladder with an abnormally thick wall, sometimes with a double wall, and on the presence of sludge. Immediate cholangiography revealed spontaneous perforation in 4 patients who were operated upon at once. The other patients were treated by percutaneous cholecystostomy only with apparent success. The frequency, physiopathology, diagnosis and treatment of acute post-aggressive cholecystitis are discussed, with special reference to this new therapeutic approach. PMID- 2931681 TI - [Aortic valve stenosis. Prenatal diagnosis. A case]. AB - Closed aortic valvotomy through the left ventricular apex could be performed in a 3-day old child thanks to an echocardiographic diagnosis in utero, at 32 weeks, of aortic stenosis, confirmed immediately after birth. The functional and echocardiographic results 5 months after the operation are excellent. This case shows that the prenatal diagnosis of cardiac malformation is feasible and facilitates an early treatment in the post-natal period. PMID- 2931682 TI - [Flat angioma. Therapeutical value of the laser]. AB - Following a summary of the principles of quantum physics required to understand how lasers work, the main lasers used in therapeutics are described, together with their characteristics. Only the argon laser is used in the treatment of port wine stains. The selection of cases for laser treatment is based on such criteria as colour of the lesion, speed of recoloration and patient's age. Local complications are sometimes observed. The argon laser undoubtedly constitutes a progress in the treatment of port wine stains, a condition where surgery remains disappointing. PMID- 2931683 TI - [Reimplantation of the subclavian artery into the common carotid artery]. AB - Since 1973, transposition of the subclavian artery into the common carotid artery has been the technique of choice to treat prevertebral occlusive subclavian lesions. However, the haemodynamic results in the vertebral artery were far from perfect, as shown by immediate post-operative ultrasonic examinations. This has been corrected by a technical modification: the subclavian artery is severed flush with the vertebral artery lying obliquely downward and medially, which is equivalent to reimplanting a "double-barrelled" vessel (the vertebral and subclavian arteries) into the common carotid artery. PMID- 2931684 TI - [Value of hepatic biopsy in pulmonary and extrapulmonary forms of sarcoidosis in children]. PMID- 2931685 TI - [Cutaneous microabscesses caused by Scedosporium apiospermum]. PMID- 2931686 TI - [Primary pulmonary lymphoma on a cicatrix]. PMID- 2931687 TI - [Value of rectal biopsy in parasitology in children]. PMID- 2931688 TI - [Interpretation of the labial salivary gland biopsy in the elderly]. PMID- 2931689 TI - [Lyme disease without arthritis: presence of antiBorrelia burgdorferi antibodies in meningoradiculitis following chronic erythema migrans]. PMID- 2931690 TI - [Do intrauterine growth retardation and low ponderal index predict various aspects of neonatal morbidity?]. PMID- 2931692 TI - [Fatal tetanus 6 months after incomplete primary vaccination]. PMID- 2931691 TI - [Abdominal injuries caused by seat belts]. PMID- 2931693 TI - [Incidence of veno-occlusive diseases of the liver after bone marrow graft]. PMID- 2931694 TI - [From localized myositis with eosinophilia to the focal form of Shulman's syndrome]. PMID- 2931695 TI - [Images of medical popularization at the end of the nineteenth century. "La medecine illustree" (1887-1889)]. PMID- 2931696 TI - [Benign mastopathies and breast carcinogenesis: a reappraisal]. PMID- 2931697 TI - [The CO2 laser: a new instrument for intracranial neurosurgery]. AB - Since 1983 we have been using an 80 watts CO2 laser unit (Ercelas 80, Robert et Carriere Biomedical) routinely in some neurosurgical procedures. Fifty tumours (34 intracranial, 4 intraorbital and 12 intraspinal) have been operated upon with laser. The CO2 laser appears to be particularly useful to excise solid tumours, such as meningiomas and neurinomas. When these lesions are located in the posterior fossa or lying deeply near highly functional or vital supratentorial structures (e.g. carotid arteries, optic nerves, chiasma), the laser beam should be coupled with an operating microscope. Laser being a non-touch technique, the tumour can be removed with minimal trauma to healthy tissues. Depending on the output power, the laser beam coagulates, cuts or vaporizes the target lesion. PMID- 2931698 TI - [Compressive pericardial effusion after heart surgery in the adult. Contribution of bidimensional echocardiographic findings]. AB - In series of 1450 consecutive cardiopulmonary bypasses for cardiac surgery in adults, we observed 20 cases of post-operative compressive pericardial effusion. The effusion occurred some time after the thoracic drains were removed and had to be evacuated. Two-dimensional echocardiography proved essential to the diagnosis : it easily detected the lesion even when clinical symptoms were misleading but above all, it demonstrated, in our series, that the classical post-operative "tamponade" is a specific entity consecutive to posterior, circumscribed, small volume effusions which mainly compress the left cardiac cavities. PMID- 2931699 TI - [Effects of cholecystectomy on functional signs associated with cholelithiasis]. AB - Two hundred hospital patients with gallstones who had been cholecystectomized on account of typical biliary colics were investigated for migraine, headache, malaise, vertigo, flatulence, diarrhoea or constipation 2, 6, 12 and 24 months after the operation. The study showed that these symptoms are common in patients with biliary lithiasis, particularly women, and that their frequency increases with the duration of the disease. The beneficial effects of cholecystectomy are uncertain and appear to decrease with time ; only 30% of the patients seemed to improve after surgery. It is concluded that these symptoms betray real functional disorders, that cholecystectomy is not the appropriate treatment for them and that any improvement observed may be credited to the placebo effects of the operation. PMID- 2931700 TI - [Role of prostaglandins and thromboxanes in cardiovascular physiopathology]. AB - Prostaglandins and thromboxanes originate from lipid metabolism. Their precise role remains obscure despite our better understanding of their potent pharmacological properties reflected in their potent biological activities. Prostaglandins are most probably involved in various cardiovascular diseases, although few satisfactory methods are available to evaluate such a role in vivo. The fact that most antithrombotic drugs interfere with the arachidonic acid cascade provides a rationale to their mode of action and their use. The development of drugs acting more selectively on arachidonic acid metabolism should constitute a therapeutic improvement in cardiovascular diseases. PMID- 2931701 TI - [Meningitis caused by Campylobacter fetus fetus. A case report]. PMID- 2931702 TI - [Factor XII deficiency and/or anticoagulant treatment at the site of an intracerebral hematoma]. PMID- 2931703 TI - [Diagnosis of trisomy 21 during the first trimester of pregnancy by a trophoblast specimen]. PMID- 2931704 TI - [Immunodeficiency syndrome, acquired post-transfusionally in a non-hemophiliac]. PMID- 2931705 TI - [A rare tumor: reparative giant cell granuloma of the mandible]. PMID- 2931706 TI - [Association of Biermer's anemia with chronic myeloid leukemia. A case report]. PMID- 2931707 TI - [Abdominal scanography in metastatic adenocarcinomas with unknown primary location. Results of a prospective study]. PMID- 2931708 TI - [Prenatal diagnosis of Fanconi's anemia]. PMID- 2931709 TI - [Leydig cell tumor. Diagnostic value of testicular echography]. PMID- 2931710 TI - [Mycoplasma pneumoniae pneumopathy with severe anemia and erythema nodosum]. PMID- 2931711 TI - [Anaphylaxis to chymopapain induced by exertion]. PMID- 2931712 TI - [Rhabdomyolysis exhibiting few symptoms complicated by acute renal insufficiency]. PMID- 2931713 TI - [Embolism potential of left ventricular post-myocardial infarct thrombosis detected by bidimensional echography]. PMID- 2931714 TI - [Meningitis from Lyme disease, diagnosed in Marseilles]. PMID- 2931715 TI - [Hypothalamic hamartoma associated with panhypopituitarism]. PMID- 2931716 TI - [Polyradiculoneuritis after tick bites. Possible role of a new pathogenic agent in man: the Avalon virus]. PMID- 2931717 TI - [Characteristics of the epidemiology of tuberculosis and the organization of present-day tuberculosis control]. PMID- 2931718 TI - [Characteristics of recurrent tuberculosis of the respiratory organs among the rural population]. PMID- 2931719 TI - [Results of mass screening of rural adolescents using the Mantoux test with 2 TU of PPD-L]. PMID- 2931720 TI - Phorbol 12-myristate 13-acetate and insulin increase the concentration of fructose 2,6-bisphosphate and stimulate glycolysis in chicken embryo fibroblasts. AB - Incubation of chicken embryo fibroblasts with mitogenic concentrations of insulin for 24 hr or with the tumor promoter phorbol 12-myristate 13-acetate for 6 hr stimulated lactate release and 3-O-methylglucose uptake. Insulin also increased the Vmax of 6-phosphofructo-1-kinase (ATP:D-fructose-6-phosphate 1 phosphotransferase, EC 2.7.1.11). Both agents increased the concentration of fructose 2,6-bisphosphate and the activity of 6-phosphofructo-2-kinase (EC 2.7.1. ), the enzyme that catalyzes the synthesis of this stimulator of 6-phosphofructo 1-kinase. These changes provide an explanation for the stimulation of glycolysis by insulin and phorbol esters. In contrast to the situation in rat liver, fructose 2,6-bisphosphate concentration did not decrease after cyclic AMP treatment. Incubation of cells with phorbol ester analogues or with glycerol derivatives that are known to stimulate, or to bind to, protein kinase C did increase the concentration of fructose 2,6-bisphosphate, suggesting that the stimulation of 6-phosphofructo-2-kinase by phorbol 12-myristate 13-acetate is mediated by protein kinase C. PMID- 2931721 TI - Effect of DNA polymerase I and DNA helicase II on the turnover rate of UvrABC excision nuclease. AB - UvrABC excision nuclease (UvrA, UvrB, and UvrC proteins) of Escherichia coli removes nucleotide mono- and diadducts from DNA in the form of oligonucleotides 12 or 13 bases long. We find that the purified enzyme dissociates from DNA very slowly, if at all, in the absence of other proteins implicated in excision repair. Addition of DNA polymerase I and helicase II (UvrD protein) to the reaction mixture stimulates the turnover rate of the excision nuclease to a level comparable to that observed in vivo. PMID- 2931722 TI - Multiple chemical forms of hepatitis B surface antigen produced in yeast. AB - Hepatitis B surface antigen (HBsAg) has been extracted from yeast cells that produce HBsAg. These cells contain the gene for surface antigen carried on a plasmid that replicates in the cells. Analysis of the yeast-derived HBsAg by sucrose gradient centrifugation and by polyacrylamide gel electrophoresis shows that the antigen that is initially released from yeast cells is a high molecular weight aggregate of the fundamental Mr 25,000 subunit. Unlike HBsAg derived from human plasma, the yeast antigen is held together by noncovalent interactions and can be dissociated in 2% NaDodSO4 without the use of reducing agents. During in vitro purification of the yeast antigen, some disulfide bonds form spontaneously between the antigen subunits, resulting in a particle composed of a mixture of monomers and disulfide-bonded dimers. Treatment with 3 M thiocyanate converts the 20-nm particles into a fully disulfide-bonded form that is not disrupted in NaDodSO4 unless a reducing agent is added. This disulfide-bonded particle resembles the naturally occurring, plasma-derived surface antigen particle, and the in vitro formed particle has been used to prepare a vaccine for humans against hepatitis B virus infection. PMID- 2931724 TI - Some principles of membrane structure. PMID- 2931723 TI - H-2-incompatible bone marrow chimeras produce donor-H-2-restricted Ly-2 suppressor T-cell factor(s). AB - To study adaptive-differentiation phenomena of T lymphocytes, suppressor T-cell factors (TsF) produced by Ly-2+ splenic T cells from fully allogeneic mouse bone marrow chimeras were analyzed. AKR mice irradiated and reconstituted with B10 marrow cells (B10----AKR chimeras) produced an Ly-2+ TsF after hyperimmunization with sheep erythrocytes. The TsF suppressed primary antibody responses (to sheep erythrocytes) generated with spleen cells of mice of H-2b haplotype but not those of H-2k haplotype. Thus, this suppressor factor was donor-H-2-restricted. The immunoglobulin heavy chain variable region gene (Igh-V)-restricting element was not involved in this form of suppression. Similar results were obtained when TsF from B6----BALB/c and BALB/c----B6 chimeras were analyzed. The TsF from B10--- AKR chimeras suppressed responses of B10.A(3R) and B10.A(5R) mice but not those of B10.A(4R). This finding showed that identity between the factor-producing cells and target spleen cells is required on the left-hand side of the E beta locus of the H-2 region and that the putative I-Jb locus is not involved in this form of suppression. The present results support the postulate that post-thymic differentiation in the presence of continued or repeated stimulation with antigen and donor-derived antigen-presenting cells generates donor-H-2-restricted T-cell clones that may predominate within the repertoire of the specific antigen being presented. PMID- 2931725 TI - Membranes and the response to insulin. PMID- 2931726 TI - The biochemistry and physiology of the muscle cell. PMID- 2931727 TI - Fetal rat islet insulin deficiency following maternal administration of streptozotocin. AB - Pancreatic islets were isolated from the fetuses of normal rats and rats made diabetic by the iv administration of streptozotocin (STZ) on either Day 3 or 5 of pregnancy. Of the rats made diabetic on Day 3, one group also received insulin injections at the appearance of glucosuria. Maternal blood glucose on Day 20 of gestation was significantly different in the diabetic rats (405 +/- 27 mg/dl) from the normal (97 +/- 1 mg/dl) and insulin-treated diabetic rats (69 +/- 9 mg/dl). While fetal weight was significantly decreased in the STZ-treated rats (2.64 +/- 0.13 g vs 3.52 +/- 0.05 g for the control group, P less than 0.005), fetal glucose was significantly higher in the STZ-treated than in normal pups (342 +/- 11 vs 35 +/- 1 mg/dl, P less than 0.005). Both fetal weight and glucose were normalized by insulin treatment: 3.16 +/- 0.18 g and 31 +/- 7 mg/dl, respectively. Insulin release from fetal islets of diabetic dams was blunted after a week in culture both in basal and stimulated conditions. After 2 weeks in culture, there was partial recovery in the insulin response to glucose but it did not equal to that measured in fetal islets from the normal and insulin-treated diabetic rats. These data suggest maternal hyperglycemia severely impairs fetal weight and insulin release from fetal rat islets in vitro, and correction of the hyperglycemia by insulin treatment not only improves fetal weight and glucose concentrations, but it also normalizes insulin release from fetal rat islets in vitro. PMID- 2931728 TI - Genetic restriction in the suppression of erythropoiesis and the role of Ia-like antigens in progenitor differentiation. PMID- 2931729 TI - Serotonin and vascular reactivity. AB - Serotonin causes contraction of the vascular smooth muscle cells in most blood vessels studied in vitro. This contraction is mainly due to activation of S2 serotonergic receptors. The monoamine can cause relaxation through activation of serotonergic receptors, different from the S2-serotonergic receptor and located on endothelial cells, or through an inhibitory effect on adrenergic neurotransmission. In certain blood vessels, the contractile effects can be markedly enhanced by hypoxia or moderate cooling. At low concentrations serotonin amplifies the vasoconstrictor responses to other vasoactive substances. Ultimately the effect of serotonin on vascular constriction is defined by the balance between these different actions. In the intact organism under normal conditions serotonin may play a modulatory role but exacerbation of the contractile effects because of hypersensitivity of the smooth muscle cells, local physical or humoral factors or loss of the relaxatory ability may lead to abnormal tissue responses. Thus, serotonin-induced vasoconstrictor responses may play a role in the etiology of vasospasm and peripheral vascular diseases, in particular at sites of endothelial lesions. Both the vasoconstrictor and the platelet aggregating effects of serotonin combined with its accelerated turnover may be important in the induction and maintenance of the augmented peripheral vascular resistance in arterial hypertension. PMID- 2931730 TI - Diclofenac and pirprofen modify pituitary and hypothalamic beta-endorphin concentrations. AB - We provide evidence that both Diclofenac and Pirprofen, two cyclooxygenase inhibitors with a potent analgesic effect both in the experimental animal and in man, induce a significant and long lasting decrease in pituitary beta-endorphin concentrations, together with an increase of the hypothalamic concentrations of the peptide. We suggest that this effect might participate in the potent analgesic effect of the two compounds, that exceeds the one expected by drugs of this class. PMID- 2931731 TI - The chromaffin vesicle: a model secretory organelle. PMID- 2931732 TI - Regulation of secretion from adrenal chromaffin cells. PMID- 2931733 TI - Influence of thyroxine and propylthiouracil administration on the intake of maternal milk in sucklings of the laboratory rat. AB - Young laboratory rats received a daily subcutaneous injection of thyroxine (T4) and propylthiouracil (PTU) in saline, from birth until the period of spontaneous weaning. The rate of growth and the time of eye opening as well as the spontaneous weaning was assessed. The intake of maternal milk was followed directly, i.e. by the transport of 85Sr in maternal milk from the maternal body to the sucklings. In the young treated with T4 the eyes opened earlier than in the young treated with PTU. The body mass differed in both groups between the 4th and 20th day of life (the T4 pups were heavier). The 85Sr transfer in maternal milk was higher in the PTU young from the 22nd day of life. The PTU sucklings weaned spontaneously one week later than those receiving T4. A hypothesis has been proposed on the primary significance of maturation of oral mechanisms of sucking for spontaneous weaning. PMID- 2931734 TI - Extracellular K+ and Ca2+ activities measured during the action of negative pressure under a suction electrode placed on the surface of frog heart ventricle. AB - The application of negative pressure of -40 kPa (-300 mm Hg) for 10 min under a suction electrode placed on the surface of the spontaneously beating frog ventricle changed the extracellular potassium activity (aoK+) in three phases: a phase of rapidly rising aoK+, a slowly decaying phase and a phase of slowly rising aoK+. The changes reversed when suction was discontinued during the rapidly rising and decaying phase, but were not reversed during the slowly rising phase. Calcium extra-cellular activity (aoCa2+) decreased between -5 and -13 kPa, but increased during the higher pressures. The results indicated that injury of the ventricular tissue caused by a suction electrode elevated aoK+ and altered aoCa2+. PMID- 2931735 TI - Effect of repeated exercise on postnatal development of the noradrenaline content of the albino rat heart, spleen and skeletal muscle. AB - The authors studied the effect of repeated elevation of sympathetic activity on the postnatal development of the noradrenaline content of tissues of the albino rat. Between the ages of 15 and 29 days, young rats were forced to swim in water heated to 25 degrees C, 3 X 30 min on weekdays and 1 X 30 min on Saturdays and Sundays. At 30, 45 and 65 days, the noradrenaline content of the tissues was determined spectrofluorometricaLly by the trihydroxyindole method. The noradrenaline content of the heart of trained rats was higher than in the controls in all the given age groups and the size of the absolute difference rose with advancing age. The noradrenaline content of the spleen developed similarly. Repeated exercise did not lead to an increase in the noradrenaline content of skeletal muscle. The results show that the repeated elevation of the activity of sympathetic adrenergic neurones which occurs in young rats during exercise is a long-term factor stimulating the development of sympathetic innervation of the heart and spleen. The development of the neurones innervating skeletal muscle was not stimulated, probably because the activity of these neurones is not increased by stress. PMID- 2931736 TI - Choline acetyltransferase activity and distribution in rat hearts after bilateral cervical vagotomy. AB - The activity of choline acetyltransferase (ChAt; E.C. 2.3.1.6) measured as the bromoacetylcholine-sensitive portion of the maximal rate of acetylcholine synthesis has been determined in homogenates of nine regions of the heart of control rats and rats sacrificed 72-74 h after bilateral cervical vagotomy. When related to the content of protein, the activity of ChAT was lowered by 30% in the atria and unchanged in the ventricles of vagotomized rats. The highest absolute decline caused by vagotomy was observed in the sinoatrial region; it was somewhat less in the rest of the right atrium and in the interatrial septum and considerably less in the left atrium. It is concluded that preganglionic parasympathetic fibres supply mainly the sinoatrial region and the right atrium, and that they do not branch to the ventricles. Preganglionic ChAT nts about 30% of total ChAT activity in the atria. The sinoatrio-ventricular gradient in the distribution of ChAT in the heart is due to uneven distribution of both the pre- and postganglionic ChAT pools (i.e., of both the pre- and postganglionic cholinergic nerve fibres and nerve cell bodies). PMID- 2931737 TI - The acute and the chronic effects of imipramine on the spontaneous motility in chick embryos. AB - The effect of imipramine on the spontaneous motility and development of chick embryos was studied from the 4th to the 19th day of incubation. On acute administration (a single dose of 12.5 of 25 mg/kg egg weight), imipramine already induced significant depression of spontaneous motility in 11-day embryos--an effect which increased significantly after the 15th day of incubation. The similar effect of imipramine in spinal embryos testifies to its direct action on the spinal cord and draws attention to certain details of the role of supraspinal structures of the CNS in the acute effect of imipramine. The chronic administration of imipramine showed that it had an almost 100% lethal effect from 4th to the 7th day of incubation. Between the 8th and the 10th day it caused longlasting depression of spontaneous motility. When it was administered between the 11th and 16th day of incubation, no significant effect on the development of spontaneous motor activity was found in chick embryos. PMID- 2931738 TI - Maze-escape learning and memory during rat ontogeny. AB - With the method of a simple automatic rectangular maze the development of escape reaction was studied in albino rats aged 3 weeks to 3 months as well as memory retrieval within 24 h and then after one month. Learning of escape improves sharply between the 3rd and 4th postnatal week, and then, with the exception of week 8, remains approximately on the same level. Memory retrieval up to 24 h is not significantly influenced by age or sex, but is best immediately after learning interval of 10 min and the poorest after 24 h, except the age of 5 weeks, where it is best in 3 and 6 h after learning. One-month retention of maze escape improves during development except in animals trained at the age of 6 weeks in which the level is lower than in all other investigated groups. One month memory retrieval in animals taught at the age of 4 weeks is influenced by the time of the first retention test with the best values in animals tested for the first time after 3 h and poorest in animals tested after 24 h after learning. Animals trained at 5 weeks had a marginally better result after the one-month retention test in females, perhaps due to the influence of sexual maturation on memory traces. This was not observed in the other age groups. Attention is drawn to the different development of learning and memory of various types of conditioned reactions stemming from the difference in their complexity. PMID- 2931739 TI - Chick and quail specific pattern of endplates and fibre-types in the plantaris muscle. AB - Species-specific endplate distribution and fibre-type pattern were found in the plantaris muscle (PL) of the chick and quail. The PL is proposed as a model for studies of nerve-muscle interactions in chimeras. PMID- 2931740 TI - The adrenocortical function of alloxan-induced diabetic rats. AB - The purpose of this study is to investigate the adrenocortical function of alloxan-induced diabetic rats. Male rats of Wistar strain, weighing 200-250 gm were used. The results indicated that the adrenocortical response to stress and exogenous corticotropin (ACTH1-24) is decreased during the early diabetic stages (up to 6 days). Evidence from in vivo and in vitro studies shows that the depression is caused by the toxicity of alloxan on the adrenal cortex cells and not by the sudden rise of blood glucose levels. Streptozotocin (another diabetogen) has the same effect as alloxan on adrenal cortex cells. PMID- 2931742 TI - Antegrade catheterization of the superficial femoral artery. AB - A simple method of selective catheterization of the superficial femoral artery (SFA) following antegrade puncture of the common femoral artery is described. The method entails using a Cope-type dilator introducer, which directs the guide wire from its side hole into the SFA while the tip is secured in the deep femoral artery. PMID- 2931741 TI - Childhood diagnostic and handicap registers--a way forward. PMID- 2931743 TI - Antegrade selective catheterization of the superficial femoral artery using a movable-core guide wire. AB - A simplified method of selective antegrade catheterization of the superficial femoral artery using a movable-core guide wire is described. This technique obviates the need for multiple catheter and guide wire manipulations and exchanges when preferential passage of the guide wire into the profunda femoral artery occurs following antegrade common femoral artery puncture. PMID- 2931744 TI - Effect of indomethacin on proteinuria in rats with autologous immune complex nephropathy. AB - Although non-steroidal anti-inflammatory agents have been used to reduce levels of urinary protein excretion in patients with the nephrotic syndrome, the general usefulness of these drugs in proteinuric states remains unclear. The present study was designed to confirm the efficacy and to investigate some of the mechanism/s of action of non-steroidal anti-inflammatory agents in animals with proteinuria as the result of a single form experimental renal disease. Autologous immune complex nephropathy was produced in groups of Lewis rats by the administration of autologous tubular Fx1A antigen. After marked proteinuria developed, indomethacin (8 mg/kg/day) was administered orally to one group of animals for five days while a control group received only vehicle. The level of urinary protein excretion in the indomethacin treated animals was 420 +/- 198 mg/day compared to a level of 1180 +/- 306 seen in the untreated animals (p less than 0.05). When the indomethacin-treated and control animals were compared, the reduction in proteinuria could not be found to be associated with a change in the glomerular filtration rate, urine electrolyte or osmolar excretion rates, electron microscopic appearance of the glomerular basement membrane, or a change in the glomerular permeability to neutral dextran. Treatment of animals with either sodium salicylate or lower does of indomethacin (both of which resulted also in significant falls in urinary prostaglandin E excretion rates) failed to reduce the levels of proteinuria. Thus, indomethacin was capable of reducing the levels of protein excretion in rats with autologous immune complex nephropathy although the mechanism of action of this agent remains unclear. PMID- 2931745 TI - [Suppressive activity of lymphocytes and monocytes in patients with syphilis]. PMID- 2931746 TI - Percutaneous transluminal renal angioplasty: follow up studies on renovascular hypertension. PMID- 2931747 TI - [Evolutive modalities unique to acute pancreatitis: chronic peritoneal and pleural effusions; migrating pseudocysts]. PMID- 2931748 TI - [Pathology of Meckel's diverticulum--clinical, morphological and therapeutic aspects]. PMID- 2931749 TI - [Subphrenic abscesses; anatomico-clinical and therapeutic considerations]. PMID- 2931750 TI - [Characteristics of cholangitic hepatic abscesses]. PMID- 2931751 TI - [Primary and recurrent varices of the communicating veins at the level of the thigh and perineum]. PMID- 2931752 TI - [Ozone therapy, a new method of treating chronic obliterating arteriopathies]. PMID- 2931753 TI - [Esophagoplasty using the transverse colon in children]. PMID- 2931754 TI - [Scapulectomy; elements of the surgical technic]. PMID- 2931755 TI - [Amebic abscess of the liver]. PMID- 2931757 TI - [Primary testicular carcinoid tumor]. PMID- 2931756 TI - [Lumbar neurofibroma]. PMID- 2931758 TI - [Neglected sectioning of the patellar tendon repaired with a dacron arterial graft]. PMID- 2931759 TI - [Rare complication of acute appendicitis]. PMID- 2931760 TI - [Surgical correction by duodenal diversion of postoperative gastric and esophageal alkaline reflux]. PMID- 2931761 TI - [Our experience in treating scapular bone tumors]. PMID- 2931763 TI - [Procedure for mesosigmoidopexy in treating sigmoid volvulus]. PMID- 2931762 TI - [Surgical treatment of deformities due to burns of the hands]. PMID- 2931764 TI - [Determination of atypical pseudocholinesterase]. PMID- 2931765 TI - [100 years of the use of cocaine in local ophthalmological anesthesia]. PMID- 2931766 TI - [Cornea--ultrastructure and physiology (I)]. PMID- 2931767 TI - [Retinal sensitivity required for the optimal functioning of naval transport workers]. PMID- 2931768 TI - [Serology of toxoplasmosis in eye infections]. PMID- 2931769 TI - [Glaucoma in aphakia--etiopathogenesis, prevention and treatment]. PMID- 2931770 TI - [Value of dynamic infrared telethermography in diagnosing eye tumors]. PMID- 2931771 TI - [Treatment of amblyopia in unilateral myopia and accentuated anisomyopia]. PMID- 2931772 TI - [Episurgery of the artificial crystalline lens implant]. PMID- 2931773 TI - [Cataract extraction in eyes with subconjunctival antiglaucoma fistulae]. PMID- 2931774 TI - [Ocular manifestations in progressive facial hemiatrophy (Parry-Romberg syndrome)]. PMID- 2931775 TI - [Postcontusion pigmentary epitheliopathy]. PMID- 2931776 TI - [Sjogren's syndrome. Etiopathogenetic comments on 3 clinical cases]. PMID- 2931777 TI - [Dilated cardiomyopathy caused by Chagas' disease]. PMID- 2931778 TI - [Anterior systolic movement of the mitral valve in the absence of hypertrophic myocardiopathy]. PMID- 2931779 TI - [Prenatal echocardiographic diagnosis of a case of atrioventricular septum defect]. PMID- 2931780 TI - [From the care of cripples to the rehabilitation of the physically handicapped]. AB - Starting out from describing an orthopaedic institute with an orthopaedic rehabilitative approach, established in 1780 by Venel in the Suisse canton of Waadt, a historical retrospective is given of the field of rehabilitation of the physically disabled, going back for some notable industrial and social medicine aspects to Graeco-Roman times. Reference is in particular made to the peculiarities of 19th century private, residential care, and the development of modern-day facilities for persons with a physical disability is outlined. PMID- 2931781 TI - [The beginnings of care for cripples in Lower Franconia and its development into the modern rehabilitation of the physically handicapped]. AB - On the example of Lower Franconia, a predominantly rural region which has maintained its boundaries in both world wars, the author describes the historical development of services for disabled persons since the beginning of this century. Jakob Riedinger may justly be termed the father of cripple care in Lower Franconia, having initiated the establishment, in 1910, of the first vocational rehabilitation facility for physically disabled people in Wurzburg. Starting out from the provision of vocational services, further developments in particular after the 2nd world war entailed a growing recognition of the psychosocial situation of disabled persons as the basis of rehabilitative action. Several facilities have hence been established for providing holistic, early services for the physically disabled, where educators, physiotherapists, occupational and speech therapists, social workers and psychologists are involved, along with the orthopaedic doctor, in the care of physically disabled children and youths. PMID- 2931782 TI - [The development of legal premises in the rehabilitation of the physically handicapped from Bismarck to today--a brief overview]. AB - The legal bases for rehabilitation and integration of the physically disabled have developed from public welfare provisions, the beginnings of disability care having been part of public poor relief schemes. Ensueing developments range from cripple care programmes to today's efforts to establish a uniform social code, which is expected to benefit the individual disabled person by bringing about a marked simplification of the current legal and administrative situation. The extension of the scope of rehabilitative efforts, which since Bismarck's time had comprised nursing and institutional care in cases of physical and mental ailings within the framework of poor relief, had initially occurred outside Prussia by including education and vocational training for disabled people (the beginnings of "rehabilitation"). A more comprehensive approach to disability care in the sense of extended assistance was embodied in the Prussian cripple welfare act of 1920. The Federal Social Assistance Act of 1962, in the final analysis, had developed from this tradition. This 1962 act not only established a duty to provide public welfare but also gave those concerned a legal title to this kind of assistance. PMID- 2931783 TI - [Basic formulation of the tasks of special education in rehabilitating the physically handicapped]. AB - Special educational reflexion is directed at, and analyses, the ever specific situation of the child with a physical disability, in order to attain the conditions enabling subjective and intersubjective reality to be formed and stabilized. 'Dealing with the external world' means complex and differentiated perception and internalization, particularly, subjectively relevant and meaningful activity: all this describes the individual learning and achievement behaviour of the child with a physical disablement. 'Achievement' becomes a category of high subjective significance, which requires constant intersubjective recognition. Motor behaviour as an objectifyable phenomenon must be distinguished from personal motor activity, at however limited a level of constitutional and functional motor competency it may occur. Expectation of success, and the avoidance of failure, are intrinsic constituents of educational reality in dealing with a physically disabled child. As Krappmann puts it, the achievement the individual must accomplish as a condition for enabling his participation in communication processes to occur, is designated as the category of identity. PMID- 2931784 TI - [Basic school problems for the physically handicapped]. AB - Describing the current status of the "school for the physically disabled" and the developmental tendencies observable in this type of school, the author in particular contrasts recently evolved practice with the existing legislative and administrative orientations. It is found that on account of demographic and socio medical developments and pressures, actual practice has gone far beyond the administrative framework, entailing a need to catch up in terms of conceptual thinking and administrative provision. This need to catch up essentially pertains to conceptual integration of the consequences that arise from the inclusion of students with increasingly severe disablement, to questions of occupational outlook for physically handicapped students with learning disabilities, adequate conclusions as regards creating a flexible organizational structure in the individual school, as well as the problems involved in statutory provision relative to the necessary paramedical services and the linkages between therapy and education, also in terms of cooperation between school and public health services. PMID- 2931785 TI - The mental health needs of individuals with severe physical disability: a consumer advocate perspective. PMID- 2931786 TI - [Enzyme metabolic and contractile activities of 30 pig muscles. Relation with the final ph attained after death]. AB - This paper presents a study of the metabolic and contractile types of 34 samples from 30 muscles in five crossbred Pietrain-Large White pigs 6 to 7 months old. The activity of the following enzymes was measured: glyceraldehyde-3-phosphate dehydrogenase (GAPDH), lactate dehydrogenase using high (LDH-h) or low (LDH-b) pyruvate concentrations in the reaction medium, citrate synthase (CS), and myofibrillar Ca-Mg activated ATPase. Haeminic iron and ultimate pH (pHu) were measured on the same samples. The results showed a negative, rather linear relationship between GAPDH, LDH and ATPase activities on the one hand and CS and haeminic iron on the other. Rather high correlations (r = 0.7 to 0.8) were observed between metabolic and contractile criteria and pHu; the red (slow) muscles had the highest pHu. PMID- 2931787 TI - [Clinical aspects and the socio-occupational rehabilitation of schizophrenics in the Romanian capital]. PMID- 2931789 TI - [Group psychotherapy of schizophrenics]. PMID- 2931788 TI - [Schizophrenia morbidity in Cluj County]. PMID- 2931790 TI - [Reflections on the function of the social integration of schizophrenics]. PMID- 2931791 TI - [Antoine Bayle (1799-1858)]. PMID- 2931792 TI - [Laparoscopy in acute abdomen]. PMID- 2931793 TI - [Treatment of osteoarthrosis with mucarthrin]. PMID- 2931795 TI - ATP-ase activity of mitochondria isolated from needle-biopsy liver samples of diabetic subjects. AB - ATP-ase activity in mitochondria isolated from liver needle-biopsy samples was measured in 5 diabetics, aged 30-63 years and in 4 control subjects of similar age. The mitochondrial fraction was isolated by differential centrifugation of the homogenate and the ATP-ase activity was determined in the optimal conditions previously described for human liver mitochondria. The basal and Mg-stimulated ATP-ase activities were higher, while the DNP-stimulated ATP-ase activity was lower in diabetics compared to controls. The ratio of DNP-ATP-ase/Mg2+-ATP-ase was between 1-2 in diabetics and above 5 in controls. This pattern of ATP-ase activity in diabetics is indicative of mitochondrial damage. No quantitative changes in the amount of mitochondria isolated from liver (expressed in micrograms mitochondrial protein/mg wet tissue) could be noticed in diabetics compared to controls. Consequently, the alterations of ATP-ase activity is probably reflective of impairments of functional integrity of liver mitochondria in diabetics. PMID- 2931794 TI - Spontaneous and aggregated IgG induced rheumatoid factor producing cells in rheumatoid arthritis. AB - Seropositive rheumatoid arthritis (RA) patients were found to have high numbers of spontaneously occurring cells making rheumatoid factor (RF) reactive with human IgG as measured by a RF plaque forming cell (RF-PFC) assay. There was a significant positive correlation between the number of RF-PFC and both disease activity measured by the sedimentation rate and RF titer measured by the RA latex test. Aggregated IgG and pokeweed mitogen were equally effective stimulators of RF-PFC in cultures of RA peripheral blood mononuclear leukocytes. The rheumatoid ratio of helper (T4): suppressor (T8) T lymphocytes was also significantly increased over the ratio of normal controls, but this ratio did not correlate with the number of RF-PFC. Aggregated IgG or immune complexes may be responsible for stimulating RA RF-PFC in vivo. PMID- 2931796 TI - Alcoholic encephalopathies. Biochemical and neuropathological aspects. PMID- 2931797 TI - The immunodeficiency of bone marrow-transplanted patients. The effect of patient lymphocytes on the response of donor lymphocytes to mitogens and allogeneic cells. AB - Lymphocytes from patients after bone marrow transplantation (BMT) are in most cases predominantly of the Leu-2+ (cytotoxic/suppressor) phenotypes and are almost unresponsive to mitogens. In contrast, normal Leu-3+-depleted, Leu-2+ enriched lymphocyte suspensions retain approximately 50% of the mitogenic response compared with that of unseparated cells. To investigate whether this discrepancy was due to active suppression, we selected nine BMT patients from whom sufficient numbers of cells were available and whose lymphocyte phenotypes were predominantly Leu-2+ after BMT. These post-BMT lymphocytes were tested for functional suppressor activities against donor and recipient pre-BMT lymphocytes in the lymphocyte transformation test. None of these post-BMT cells suppressed the response of donor or pre-BMT cells to phytohaemagglutinin A or concanavalin A. In contrast, the response of donor cells in mixed lymphocyte cultures to HLA DR-different third-party cells was suppressed by highly X-irradiated post-BMT cells by approximately 40%. Addition of T-cell growth factor (= interleukin 2 (IL 2)) or X-irradiated donor cells to post-BMT lymphocytes partially restored the mitogenic response. These findings indicate that the early post-BMT cells lack production of IL-2 but are capable of responding to IL-2 and that the almost extinct mitogen response of these cells is due to immaturity rather than active suppression. The suppression of the allogeneic but not the mitogenic response might be explained by differences in the modes of activation; for example, the allogeneic response must involve the T-cell receptor, while the mitogenic response may not. PMID- 2931798 TI - Functional analysis of pokeweed mitogen-dependent cell interactions in murine spleen cells. I. Lack of B-cell mitogenicity and low frequency of effector helper T cells. AB - The nature of lymphocyte responses on addition of pokeweed mitogen (PWM) to normal murine spleen cells was studied in low cell density cultures. PWM, over a wide range of concentrations, stimulated proliferation in a set of cells roughly 10-fold smaller than the lymphocyte populations responding to either concanavalin A or lipopolysaccharide. PWM also induced a relatively small number of B lymphocytes in these cultures to mature to Ig-secreting plaque-forming cells (PFC). Proliferative and PFC responses were completely abrogated by T-cell removal from normal spleen cell cultures. Moreover, cell mixture and irradiation experiments demonstrated that B lymphocytes do not proliferate in response to PWM, even in the presence of an excess of normal T cells, suggesting that PFC development results from terminal maturation without proliferation. Finally, parallel titrations of cloned helper cells, normal splenic T cells or T-cell blasts induced by PWM showed that the poor B-lymphocyte responses in normal spleen cell cultures is due to the very low frequency of competent helper cells in these populations. PWM, however, was competent to activate and expand this set of helper lymphocytes in primary cultures. PMID- 2931799 TI - T-lymphocyte subsets and HLA-DR-expressing cells in the osteoarthritic synovialis. AB - Rheumatoid and osteoarthritic synovial membranes biopsied at operations were analysed in frozen sections with an immunohistochemical monoclonal antibody technique. It is evident from this investigation that immunocompetent inflammatory cells such as HLA-DR-expressing non-T cells and T cells in general occur even in the osteoarthritic synovial membrane, though to a lesser degree than in rheumatoid arthritis. In about half of the osteoarthritic synovial membranes these T cells were clustered in follicle-like formations. In both diseases, most of the T cells were helper/inducer T cells whereas cytotoxic/suppressor T cells occur sparsely and almost exclusively in rheumatoid arthritis. PMID- 2931800 TI - [Fibrinolysis therapy in massive lung embolism. Experiences in 10 patients 1982 1984]. AB - Between October 1982 and July 1984 systemic thrombolysis was carried out in 10 patients (5 males and 5 females aged 19 to 66 years) with massive pulmonary embolism (PE). Mean thrombolytic treatment duration was 77 hours. The main fibrinolytic agent used (9 cases) was streptokinase. Sequential treatment with streptokinase and urokinase was given to 2 patients and urokinase alone to one. 5 patients received porcine plasmin additionally, and one patient BRL 26921 (streptokinase-plasminogen complex) and human plasminogen. Pulmonary arterial pressures were recorded serially. Pulmonary angiograms were obtained before, occasionally during and after thrombolysis. Pulmonary arterial pressures (systolic: p less than 0.01, diastolic: p less than 0.05, mean: p less than 0.01, paired t-test, two tailed) and pulmonary angiograms (p less than 0.001, paired t test, two tailed) all showed significant improvement. Thrombolytic treatment had to be discontinued in two patients due to side effects. Patients with the most recent PE showed the best response. Patients with recurrent PE and preexisting pulmonary hypertension showed no improvement. In PE without deep vein thrombosis (DVT), treatment duration of up to three days seems to be appropriate. In PE with concomitant DVT the treatment should be prolonged to achieve complete lysis of thrombi. PMID- 2931801 TI - Coronary vasoconstrictor effects of atriopeptin II. AB - Atrial natriuretic peptides lower arterial pressure, cardiac filling pressure, and cardiac output. In isolated, Langendorff-perfused guinea pig hearts, atriopeptin II, the 23-amino acid atrial natriuretic peptide, is also a potent coronary vasoconstrictor. The median effective dose for atriopeptin II in guinea pig hearts is 26 nanomoles, the threshold constrictor dose is 5 nanomoles, and flow nearly ceases at a dose of 100 nanomoles in perfused hearts at constant pressure. Similar concentrations of atriopeptin II also cause coronary vasoconstriction in rat and dog heart preparations. The disulfide bridge is necessary for vasoconstrictor activity; reduction of this bridge abolishes the activity, as it does the other biological activities of atrial natriuretic peptides. PMID- 2931802 TI - Selective sparing of a class of striatal neurons in Huntington's disease. AB - A distinct subpopulation of striatal aspiny neurons, containing the enzyme nicotinamide adenine dinucleotide phosphate diaphorase, is preserved in the caudate nucleus in Huntington's disease. Biochemical assays confirmed a significant increase in the activity of this enzyme in both the caudate nucleus and putamen in postmortem brain tissue from patients with this disease. The resistance of these neurons suggests that the gene defect in Huntington's disease may be modifiable by the local biochemical environment. This finding may provide insight into the nature of the genetically programmed cell death that is a characteristic of the disease. PMID- 2931803 TI - Platelet membrane proteins. AB - Studies on platelet membrane proteins during the past decade have defined a series of such components and their roles in key phenomena in hemostasis and thrombosis such as platelet adhesion and aggregation. Central among the membrane proteins is the glycoprotein group. At this time, several of these proteins have been characterized as to apparent molecular weights and subunit composition whereas sugar and amino acid composition and sequences await further studies for most of them. The absence of specific membrane glycoproteins in congenital bleeding diseases has helped to identify their functions as receptors for known ligands for binding reactions central to the hemostatic mechanism. Some of the membrane proteins may exist more or less loosely attached to each other on the surface of intact platelets, and this may be important for their functions. PMID- 2931804 TI - Chiropractic and the clinical art. AB - Chiropractic is the largest 'unorthodox' health profession in the U.S.A. It is licensed in all 50 states and its services are covered by governmental and private health insurance. Yet chiropractic remains, in the opinion of medical commentators, an unscientific healing cult. Chiropractic holds that much illness is caused, directly or indirectly, by derangements in homeostasis that result from subtle vertebral malalignments called 'subluxations'. Only a minority of 'straight' chiropractors continue to provide spinal manipulation as their only modality, while the majority 'mixers' have embraced physical therapy, vitamin supplements and a wide variety of drugless treatments. Clinical trials suggest that spinal manipulation itself has short-term benefit in back pain, but the success of chiropractic is not fully explained by that effect. The clinical art, though, as manifested in the chiropractor-patient interaction contributes greatly to chiropractic healing. This process promotes patient acceptance and validation, fulfills expectations, provides explanations and engages the patient's commitment. The same process lies at the core of the 'art of medicine'. Seeing the clinical art as it functions in chiropractic can help us to understand its independent power in medicine. PMID- 2931805 TI - Excess of folates in Huntington's chorea: a possible etiologic link. PMID- 2931806 TI - [Public health in Azerbaijan during the war years]. PMID- 2931807 TI - [Public health in Uzbekistan during the war years]. PMID- 2931808 TI - [Improvement of surgical services in hospitals of the Georgian S.S.R]. PMID- 2931809 TI - [Merits of medical workers of the Ul'ianovsk region in rendering health services to wounded soldiers]. PMID- 2931810 TI - [Remarkable feats of health professionals in the Volga region]. PMID- 2931811 TI - [Health professionals--participants in the partisan movement in the Crimea]. PMID- 2931812 TI - [The Leningrad Pediatric Medical Institute during the war years]. PMID- 2931813 TI - [Morbidity and work and living conditions of engineer-technologists]. PMID- 2931814 TI - [Effect of alcoholism on morbidity with temporary loss of work capacity]. PMID- 2931815 TI - [Efficiency of rehabilitation of patients with chronic nonspecific lung diseases by stays at health resorts]. PMID- 2931816 TI - [Participation of teachers and medical students in perfecting mass defense measures]. PMID- 2931817 TI - [Local Soviets of people's deputies in maternal and child care]. PMID- 2931818 TI - [Organization of the treatment of wounded and sick soldiers in evacuation hospitals in the Chuvash ASSR]. PMID- 2931819 TI - [Development of public health in the Komi-Perm Autonomous Okrug]. PMID- 2931821 TI - [Preventive screening programs for rural school children]. PMID- 2931820 TI - [Comprehensive approach to solving problems of primary prevention]. PMID- 2931822 TI - [A method of study of the status of medical services for children in preschool institutions]. PMID- 2931823 TI - [Control of the reproductive function of the family and its determining factors]. PMID- 2931824 TI - [Medical and demographic aspects of illegitimate births]. PMID- 2931825 TI - [Methods of improving health care of workers at industrial plants]. PMID- 2931826 TI - [Socio-demographic characteristics of persons migrating to a large industrial city]. PMID- 2931827 TI - [Health care of children and adolescents during the first few years of Soviet rule]. PMID- 2931828 TI - [Medical services to the disabled and participants in World War II in the Russian Federation]. PMID- 2931829 TI - The abdominal mechanism. AB - The abdominal mechanism, utilizing intraabdominal pressure, has been described and numericized. Simulations show that the lumbodorsal fascia under control of the abdominal muscles contributes to reduce the stress at the intervertebral joint. The musculature of the lumbar spine is of primary importance in the control of the efficiency of the spinal mechanism. The system of loading, which results in observable physiologic response, maintains the compressive load at virtually 90 degrees at the bisector of the disc for all weights and all angles of forward flexion. PMID- 2931830 TI - A review of camptocormia and an unusual case in the female. AB - Camptocormia is a rare low-back disorder involving an abnormal posture of extreme forward flexion. Most reports of camptocormia were of male military recruits during World Wars I and II. The differential diagnosis of the postural deformity, the psychologic formulation of camptocormia as a conversion disorder, and the treatments that have been used are reviewed. An unusual case of camptocormia in a female is presented to illustrate one psychologic basis and one form of effective treatment of this disorder. PMID- 2931832 TI - Paraplegia following chemonucleolysis. A case report and discussion of neurotoxicity. AB - A case report of inadvertent chymopapain introduction into the lumbar theca is reported. It led to an extensive subarachnoid and subdural hemorrhage, producing paraplegia. The neurotoxicity of chymopapain in the experimental model is reviewed and related to a clinical setting. Clinically speaking, there appears to be no tolerance for this discolytic agent either in the peripheral or central nervous system. Cerebrospinal fluid barbotage may lessen the neurologic injury by removing the enzyme when it finds its way inadvertently into the subarachnoid space. PMID- 2931831 TI - Baclofen for the treatment of acute low-back syndrome. A double-blind comparison with placebo. AB - The efficacy and safety of baclofen (30-80 mg daily) for the treatment of acute low-back syndrome were evaluated in a 14-day, double-blind, randomized study of 200 patients (100 baclofen, 100 placebo). Patients with initially severe or extremely severe symptoms (as opposed to moderate symptoms) benefitted most from treatment with baclofen. The incidence of adverse effects was significantly higher in the baclofen group; however, most were mild to moderate and disappeared in all but two patients who required a reduction in dosage, without reduced drug efficacy. Baclofen was shown to be effective, safe, and well-tolerated for the treatment of patients with acute low-back syndrome. PMID- 2931833 TI - Low-back pain. Perception and tolerance. AB - The relationship between pain modifying factors, pain duration, and the role of anxiety in low-back pain experience were studied. Three groups of patients with low-back pain were examined using the Tourniquet Pain Test, McGill Pain Questionnaire, Rating Scale of Pain Intensity, State-Trait Anxiety Inventory, and Psychological Discomfort Questionnaire. Significant differences in all measured features emerged between acute and chronic pain groups. Groups of acute and subchronic pain and groups of subchronic and chronic pain differed only in several parameters, suggesting an intermittent phase in acute pain transition into chronicity. While pain prolonged, pain experience gradually but irregularly changed, exaggerating pain perception. The changes concerned mainly emotional factors and were related to the chronicity itself. Anxiety also played a significant role. PMID- 2931834 TI - The relation of spinal x-ray to low-back pain and physical activity among 60-year old men and women. AB - X-ray findings in the thoracic and lumbar spine from 666 60-year-old men and women from a general population were related to anamnestic data and physical measurements. Disc degenerations were significantly more common among those with low-back pain (LBP) compared with those without. The corresponding calculated predictive values stressed the importance of taking precaution in interpreting the radiologic findings in the clinical situation. In several instances, there were significantly more positive (abnormal) radiologic findings among those with the heaviest work. Disc degeneration and scoliosis were particularly frequent in this regard. Absolute weight and body mass index was significantly higher in persons with spondylosis. The fingertip-floor distance was greater with higher frequency of spondylosis and L4 disc degeneration. PMID- 2931835 TI - Radiographic measurements of lumbar spinal canal size and their relation to back mobility. AB - A total of 197 men and women with history of previous back pain were radiographed and clinically examined. Measurements related to the shape and size of the spinal canal were subsequently made from the lumbar radiographs. Interarticular distance and the ratio between interarticular and interpedicular distances were significantly less in women with restriction of lumbar extension, sidebending, and rotation: not in men. Anteroposterior (AP) foraminal distances and pedicular lengths were less in men with restricted extension and sidebending, although not in women. Midsagittal diameters were not significantly less in those with restricted mobility. The radiographic differences between men and women with restricted back mobility arise partly from the sexual differences in interarticular and AP foraminal distance, the former being less in women, the latter in men. This suggests a different pathogenetic factor in the two sexes. PMID- 2931836 TI - [Asymmetrical septal hypertrophy in patients with Friedreich's ataxia]. PMID- 2931837 TI - [Distribution of histochemical types of muscle fibers in the abductor policis brevis muscle and the trapezius muscle]. PMID- 2931838 TI - [Comparative histologic, enzymohistochemical and morphometric analysis of the size of type I and type II fibers in the abductor policis brevis muscle and the trapezius muscle]. PMID- 2931839 TI - Spinal manipulation in acute backache. PMID- 2931840 TI - A comparative study of ketanserin and metoprolol in essential hypertension. AB - The role of serotonin in the pathogenesis of hypertension is interesting, and its investigation is much in vogue at present. This study compared the hypotensive effect of ketanserin, a specific 5-hydroxytryptamine receptor antagonist, with metoprolol in essential hypertension. On a double-blind basis, one treatment group (19 patients on ketanserin) was compared with another (21 patients on metoprolol). There was a significant reduction in diastolic blood pressure with both ketanserin and metoprolol (P less than 0,001). Side-effects were insignificant. One patient on metoprolol and 2 on ketanserin complained of dizziness. The dose of ketanserin was 40 mg twice a day and that of metoprolol 100 mg twice a day. Ketanserin does not appear to cause abnormal haematological values or biochemical adverse effects. It can be given to hypertensive patients with cardiac failure or bronchial asthma without adverse effects and may improve the peripheral vascular status of a hypertensive patient. PMID- 2931841 TI - Factors predicting the outcome of regional streptokinase therapy for peripheral arterial occlusions. AB - Low dosage regional streptokinase therapy has become increasingly popular as an alternative to surgical treatment in acute and chronic arterial occlusions. Success rates are reported between 70 and 100 per cent. This is surprising, considering the paucity of data in the literature regarding the type of lesion treated, objective criteria for good results and predictive factors of success. In a review of 22 acute and chronic arterial occlusions of the lower extremity treated with low dosage regional streptokinase, the outcomes were grouped as either favorable or unfavorable. A success rate of 36 per cent was achieved. The two outcome groups were compared with regard to pre-existing diseases or risk factors, indications for treatment, duration of symptoms or level of occlusion. No significant difference was found. With regard to pretreatment runoff, 100 per cent of the patients in the favorable outcome group were found to have good runoff as opposed to only 21 per cent of the patients in the unfavorable outcome group. Of the patients who also had PBD procedures, all of those in the favorable group had good runoff, and all in the unfavorable group had poor runoff. In nearly achieving statistical significance, a trend was noted establishing embolic lesions as more favorable than thrombotic lesions. We conclude that our low success rate with low dosage regional streptokinase therapy is due to our strict criteria for success and the nonselective nature of the patients we studied. As a result of these findings, we do not support the preferred use of low dosage regional streptokinase therapy in arterial occlusion. However, in patients who represent high surgical risks, a trial of low dosage streptokinase therapy seems indicated if favorable predictors of success, such as good pretreatment runoff, embolic lesion and mild symptoms, are present. PMID- 2931842 TI - The effectiveness of Nissen fundoplication in neurologically impaired children with gastroesophageal reflux. AB - Fifty-seven of 101 Nissen fundoplications during the 4-year period, July 1979 to July 1983, were performed on neurologically impaired children. Mean age at the time of surgery was 5.9 years (range 1 month to 22 years). Indications for operation included: persistent vomiting, 57 patients (100%); failure to thrive, 49 patients (86%); repeated episodes of pneumonia, 49 patients (86%); esophagitis, 18 patients (32%); hiatal hernia, 14 patients (25%); episodes of apnea, 10 patients (18%); and esophageal stricture, six patients (10%). Forty-six of the 57 patients had previously failed a standard trial of nonsurgical management. Gastroesophageal reflux was documented by barium esophagograms in 51/56 patients (91%), chalasia scans in 28/32 patients (88%), esophagitis or stricture at endoscopy in 21/23 patients (91%), and acid reflux on pH monitoring in 13/16 patients (80%). Operative management included gastrostomy in 55 of the 57 patients and this was permanent in 50. Gastrostomies had previously been performed in nine patients but had failed to provide a reliable method of enteral feeding because of chronic reflux and aspiration. The surgical complication rate was 12%. Intraoperative esophageal perforation occurred in two patients, splenic tear in one, hepatic vein laceration in one, and a tight wrap in one. After surgery, bowel obstruction from adhesions developed in one patient and a midgut volvulus in another. Five of the children have died, none from causes related to the surgical procedure. Clinical and radiologic follow-up evaluations of all survivors have been done, with a mean follow-up of 3 years. In four patients the repair was felt to be inadequate. One patient had an esophageal stricture and three had recurring episodes of pneumonia. Three children showed radiologic evidence of persistent reflux, but only two were symptomatic. Two patients required a second antireflux procedure for reflux and are now free of symptoms. Nissen fundoplication appears to be a safe and beneficial procedure in neurological impaired children. Long-term follow-up evaluation of these patients showed satisfactory growth as well as a significant decrease in pulmonary disease associated with aspiration. PMID- 2931843 TI - Gastroschisis in 106 consecutive newborn infants. AB - Primary tissue closure of gastroschisis remains controversial. Some surgeons routinely place a silicone rubber sheet silo over the exposed bowel, planning a staged closure. In the past 14 1/2 years, we have cared for 106 newborns with gastroschisis, closing the defect primarily in 80%. The success of this technique depends on enlarging the abdominal cavity and decreasing the volume of bowel that must be replaced in the peritoneal cavity. Thorough preoperative rectal irrigation should evacuate all meconium. After undermining the skin around the abdominal wall defect for only 1 cm, a midline subcutaneous fasciotomy is created from the xiphoid to the pubis. The abdominal wall is then stretched in all quadrants beginning at the flanks. The eviscerated small bowel can often be returned without enlarging the initial skin defect. The skin is closed with subcuticular absorbable sutures reinforced by long skin tapes. The small ventral hernia that results is closed at about 1 year of age. Fascia could be closed primarily in 28% of these patients, and 17% required a prosthetic pouch. The duration of postoperative ileus and length of hospital stay were statistically significantly shorter in the infants who underwent primary closure. Even though more complicated patients were included in the primary closure group, the incidence of mortality and morbidity was not higher than in patients treated with silicone rubber pouches. Deaths were inevitable in five infants with gangrenous bowel, multiple anomalies, and extreme prematurity. Deaths were related to sepsis in three infants and were the result of operative or anesthetic technique in four. Only two preoperative factors were prognostic of morbidity and mortality: gestational age (but not birth weight) and the presence of intestinal ischemia or atresia. PMID- 2931844 TI - [Effect of the method of extracorporeal heparin precipitation of plasma proteins (selective plasmapheresis) on the level of immune complexes in the blood]. AB - A study was made of the effect of selective plasmapheresis (SPP) on the concentration of circulating immune complexes (CIC). The method is based on precipitation at 4 degrees C of plasma fibronectin and associated macromolecular complexes by means of heparin. Sterile plasma of the patient is separated from the precipitate, frozen and kept at -20 degrees C till the next plasmapheresis during which it is returned to the patient instead of the donor's one. All 15 patients examined were exposed to 6 SPP with an interval made every 2 to 5 days. Six patients were diagnosed to have rheumatoid arthritis, 2 systemic lupus erythematosus, 3 hemorrhagic microthrombovasculitis, and 4 multiple sclerosis. The concentration of CIC was measured by precipitation with 3.5% polyethylene glycol before and after SPP, in some cases between sessions. All the patients with rheumatoid arthritis and systemic lupus erythematosus and 2 out of the 3 patients with hemorrhagic vasculitis showed an elevated content of CIC (greater than 0.150 Units OD). The CIC content appeared normal in all the patients with multiple sclerosis. After SPP 4 patients manifested a reduction in the CIC concentration, whereas in 6 it returned to normal. Such a time course correlated with the improvement of other clinical and laboratory findings. It was established that after the first session of SPP the CIC content sharply declined followed by a gradual increment and exceeded the initial values toward the beginning of the second session. After the second SPP the patients manifested the same tendencies. The CIC content reached a maximum by the third SPP and then fell from session to session.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2931845 TI - [Clinical effectiveness of the method of extracorporeal heparin precipitation of plasma proteins (selective plasmapheresis) in patients with immune complex pathology]. AB - The authors analyse the efficacy of extracorporeal heparin precipitation of plasma proteins (selective plasmapheresis) in patients with immune complex pathology. The method lies in extracorporeal precipitation at +4 degrees C of fibronectin, cryofibrinogen and other macromolecular complexes with the aid of heparin, followed by plasma return to the patient. The method was applied to 39 patients. Hemorrhagic microthrombovasculitis was diagnosed in 7, vasculitis paralleled by hepatosplenomegaly of unclear genesis in 1, generalized vasculitis with marked systemic manifestations in 1, immune complex vasculitis complicated by recurrent polychondritis in 1, chronic active hepatitis associated with immune complex vasculitis in 1, rheumatoid arthritis in 8, systemic lupus erythematosus in 4, spleen lymphoma and Sjogren's syndrome in 1, idiopathic amyloidosis in 2, multiple sclerosis in 10 patients. Altogether 309 sessions of selective plasmaphapheresis were carried out. The time course of the clinical and laboratory criteria of the disease activity were studied before and after each plasmapheresis session. It was ascertained that the method is highly effective in the treatment of hemorrhagic vasculitis. It is mostly used if conventional therapy with heparin, cryoplasm, and deaggregating agents appears abortive. Apparently, it is the only method that may rapidly arrest the abdominal syndrome associated with hemorrhagic vasculitis. The possibility and advisability of the use of chronic plasmapheresis are discussed. Application of the method to the treatment of rheumatoid arthritis permits reducing the dose of steroid hormones, thereby not stimulating the disease activity. The method is the therapy of choice in different diseases associated with polyvalent allergy. In amyloidosis and multiple sclerosis, the method efficacy is questionable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2931846 TI - [Comparative analysis of the effectiveness and tolerance of chrysanol and myochrysine in patients with rheumatoid arthritis (preliminary report)]. AB - Fifty patients with a significant rheumatoid arthritis (RA) were treated with gold salts for 6 months to 4 years. Patients with highly active conditions (stages II-III) and with erosive arthritis (stages IIb-IV) prevailed. Extraarticular manifestations were recognized in 76% of the patients. The efficacy of chrisanol given in a dose of 1.5 ml of a 5% solution was compared to that of myocrisin in a dose of 50 mg, i. e. 25 mg metallic gold once a week. The efficacy of the drugs was evaluated from their effects on the disease activity (clinical manifestations of the articular syndrome, ESR, morphological signs of rheumatoid synovitis) and progression (the rate of the development of erosive arthritis in hand and foot joints, the time course of serum RF content, and systemic disease manifestations). These characteristics were examined with the aid of modern ultrasonic and radionuclide research methods. The evaluations were made by the treatment onset and by months 3, 6, 12 and 18 of the treatment. Analysis of the data obtained attests to a high clinical efficacy of both the drugs exhibiting basic activity which is confirmed by a decrease in the degree of the morphological manifestations of synovitis and extraarticular signs of RA, particularly of myocarditis. A method for following up outpatients to prevent grave complications of chrysotherapy is offered. PMID- 2931847 TI - [Value of scintigraphy using T1-201 in evaluating the myocardial condition in patients with cardiomyopathy]. PMID- 2931848 TI - [Increased incidence of bites of the spider kara-kurt]. PMID- 2931849 TI - [Effect of high mountain altitude on the growth of bone marrow fibroblasts in patients with cytolytic syndromes]. AB - The efficacy of colony-formation of bone marrow fibroblasts was examined in 18 patients with pancytopenia and partial cytopenia, 5 patients with intravascular hemolysis and in 4 patients with iron deficiency anemia before and after staying in mountains at an altitude of 3,200 m. It was shown that during staying in mountains, the efficacy of colony-formation was 2 to 4 times as increased. A difference was noted in the pattern of the growth of fibroblasts in patients with intracellular cytolytic syndromes and intravascular hemolysis and iron deficiency anemia. PMID- 2931851 TI - [Intravascular blood coagulation and immune complex inflammation in patients with systemic lupus erythematosus]. AB - Immune complex inflammation associated with systemic lupus erythematosus (SLE) is attended by activation of the coagulation system up to the development of disseminated intravascular blood coagulation (the DIC syndrome). Study of the hemocoagulation in 106 patients with SLE revealed the signs of the chronic DIC syndrome that manifested itself largely by hypercoagulation, increased thrombin formation and proneness to inhibition or activation of fibrinolysis. These alterations were more demonstrable in patients with a highly active condition and lupus nephritis. The clinical symptoms of the chronic DIC syndrome in the form of hemorrhages and thromboses were seen in 27 patients. Correlations were discovered between the level of soluble fibrin-monomer complexes and characteristics of inflammatory and immunologic activity. Therefore, a close interrelationship has been shown between immune complex processes and alterations in the hemocoagulation associated with SLE. It has been also demonstrated that the DIC syndrome plays a role in the progression of lupus nephritis. PMID- 2931850 TI - [Physiological methods of treatment of patients with polycythemia vera]. AB - Based on an analysis of the data pertaining to changes in the level of erythropoietin, chalones and stress hormones in the blood of patients with polycythemia vera after bloodletings and cytapheresis it is concluded that chalones participate in the development of a remission owing to the inhibition of the clone of mutant cells. The role of stress hormones is reduced to the potentiation of the effect of chalones, that of erythropoietin to the triggering of the proliferation of the cellular clone. PMID- 2931852 TI - [Activity of short-lived suppressor lymphocytes in rheumatoid arthritis]. AB - Activity of short-lived suppressor lymphocytes was studied in 26 patients with rheumatoid arthritis. Of these, 14 patients had diverse systemic manifestations: rheumatoid nodules, polyneuropathy. Sjogren's syndrome, and Felty's syndrome. It was established that attenuation of the suppressor activity in rheumatoid arthritis is characteristic of patients with systemic manifestations, who show a high level of circulating immune complexes of rheumatoid factors. The most informative data were obtained as a result of the use of the suboptimal dose of Con A having suppressor activity. PMID- 2931853 TI - Reply to comments on two articles dealing with the teratogenicity of cyproterone acetate (CA) and medroxyprogesterone acetate (MPA) PMID- 2931854 TI - Effect of proteolysis on quantitation of plasma fibronectin concentration by two immunoassays (electroimmunoassay and immunoturbidimetric technique). AB - Quantitation of fibronectin (FN) concentration is strongly influenced by FN fragmentation with trypsin, kallikrein and plasmin. Digestion by trypsin and kallikrein leads to a progressive decline in FN detectability by the immunoturbidimetric technique to zero values but is associated with an increase in the height of rockets in the Laurell's electroimmunoassay. Plasmin mediated FN fragmentation induces a strong overestimation of the FN content by the electroimmunoassay and, at very high enzyme concentrations, provokes an underestimation of FN by the immunoturbidimetric technique. The decline in FN reactivity in the immunoturbidimetric assay coincides with the disappearance of heavy fractions migrating only slightly faster than native FN in SDS-PAGE. The increase in the height of rockets in the electroimmunoassay is the highest when fractions of intermediate rate of migration prevail in the SDS-PAGE pattern. Concomitant use of these two immunoassays can distinguish native FN from its degraded form and may possibly provide a partial explanation for discrepancies in published studies on the concentration of circulating FN in various pathological states. PMID- 2931855 TI - Platelet activation in allergic asthma. PMID- 2931856 TI - Release of heparan sulfate proteoglycans from cultured aortic endothelial cells by thrombin. AB - Anticoagulant heparan sulfate proteoglycans have been shown to be released from cultured endothelial cells. The effect of thrombin on their release was investigated. Thrombin at more than one unit/ml accelerated the release of [35S] sulfate-labeled glycosaminoglycans from cultured porcine aortic endothelial cells. The effect of thrombin reached a maximum after one hour of incubation, and was dependent on the enzyme concentration. 10 unit/ml of thrombin released approximately twice as much amount of 35S-glycosaminoglycans as did Hanks' balanced salt solution alone. When the active site of thrombin was blocked by either diisopropylfluorophosphate or hirudin, the enzyme effect was completely abolished. Released glycosaminoglycans were resistant to chondroitin ABC lyase digestions, but degraded by either heparitinase or nitrous acid treatments. Released 35S-materials were precipitated with trichloroacetic acid and shown to be degraded into smaller molecules after alkali treatment on Sepharose CL-6B gel filtration chromatography. On the other hand, thrombin treatment of 51Cr-labeled cells did not cause the release of radioactivity. These results indicate that thrombin potentiates the release of heparan sulfate proteoglycans from cultured aortic endothelial cells without causing an appreciable damage to the cells. The effect of thrombin is active site-dependent and requires a relatively high enzyme concentration. PMID- 2931857 TI - Novel plasmin inhibitors released from bovine platelets during aggregation. AB - The antifibrinolytic activity was found in the medium of platelet suspension in the process of platelet aggregation induced by thrombin, ADP and 5 hydroxytryptamine. The antifibrinolytic activity was closely associated with inhibitors in platelets, which specifically inhibited plasmin activity and not inhibited other proteases such as urokinase, thrombin and trypsin. One casein unit of plasmin activity was inhibited by the inhibitors released from approximately 10(8) platelets during the aggregation with thrombin. By the activity staining analysis, it was found that there are two kinds of plasmin inhibitors with molecular weights of 25,000 and 17,000. The physiological function of these inhibitors was discussed in relation to the formation of thrombus. PMID- 2931859 TI - [Nodulocystic acne. Treatment with isotretionin (Roaccutan)--quantitative measures of skin lipids]. PMID- 2931858 TI - [Hysteroscopy]. PMID- 2931860 TI - Insulin or increased concentration of zinc in liver, kidney or muscle does not alter the phosphoglucomutase activity in vivo. AB - Injection of insulin into mice and rabbit has been reported to convert the latent form of phosphoglucomutase (E X Zn) to an active form (E X Mg) without any net increase in the protein associated with this enzyme (Hashimoto et al., Biochem. Biophys. Res. Commun., 27 (1967) 369 and Peck et al., J. Biol. Chem. 242 (1971) 1160). Because the injection of Cd in rats causes a 2-fold increase in Zn concentration in the liver, it appeared that such treatment in mice would increase the concentration of the latent enzyme and thereby enhance the insulin induced activation of the enzyme. The results however show that insulin or Cd treatment, alone or in combination do not alter the concentrations of the 2 forms of enzyme in liver, kidney or muscle of normal or fasted mice. In all instances the conversion of the latent enzyme to its activated form required preincubation with a chelating agent. Fractionation of the tissue homogenates showed that upon Cd injection the concentration of Zn in the fractions of Mr less and 1000 increased 6-fold in liver and 3-fold in kidney, that in muscle remained unchanged. PMID- 2931861 TI - Effect of mercurials on lymphocyte functions in vitro. AB - The effect of in vitro treatment with mercurials on several functions of mouse lymphocytes was studied. When lymphocytes were cultured in the presence of mercurials, DNA synthesis induced by mitogen (concanavalin A, phytohemagglutinin P, lipopolysaccharide) and polyclonal B cell activation induced by lipopolysaccharide were strongly inhibited by methylmercuric chloride at the concentration of 10(-6) M, but mercuric chloride inhibited these functions by 50% at 10(-5) M. Furthermore, 10(-7) M methylmercuric chloride and 10(-6) M mercuric chloride inhibited mixed lymphocyte reaction by 80%. Thus, the inhibitory effect of methylmercuric chloride was 10 times stronger than that of mercuric chloride when the mercurials were present in the culture throughout the incubation. On the other hand, DNA synthesis once induced by mitogens was not significantly affected when 10(-6) M methylmercury was added during the last 3 h of the incubation. Pretreatment with 10(-6) M methylmercury for 1 h, however, showed 50% inhibition of thymidine incorporation into DNA and also reduced the rate of metabolism of phosphatidyl inositol by 50%. These results indicate that methylmercury may act on mouse lymphocytes at an early stage of transformation induced by the mitogens, while inorganic mercury failed to cause the pronounced difference in its potency of inhibition on the functions of lymphocytes by the different treatments of the cells under the various conditions used. PMID- 2931862 TI - [Hospital oral surgical care in a provincial hospital]. PMID- 2931863 TI - [Assessment of the medical status of dental outpatients using a health chart]. PMID- 2931864 TI - [Results of using Vitafluor for dental caries prevention in 1st graders in Brest]. PMID- 2931865 TI - [Effect of seasonal biorhythms on dental caries severity in children]. PMID- 2931866 TI - [The importance of studying the pathogenesis of maxillodental anomalies in the practical teaching of orthodontics to dental students]. PMID- 2931867 TI - [Development and current status of pedodontics in East Germany]. PMID- 2931868 TI - Lymphoid cell chimerism and transplantation tolerance induced by bursal and postbursal cells. AB - Transplantation of allogeneic bursal cells into cyclophosphamide-treated, immunodeficient chickens is a useful experimental model for analyzing the mechanisms of transplantation tolerance, especially because transplanted bursal cells do not produce graft-versus-host disease. In this study we have determined B-lymphoid chimerism in various lymphoid organs after transplantation of allogeneic bursal stem cells or postbursal cells, and used a variety of tests to determine presence of immunological tolerance. Transplanted bursal stem cells induced a state of stable chimerism that could easily be detected in peripheral blood and other lymphoid organs. Chimerism induced by postbursal cells was low in peripheral blood, but clearly observable in other lymphoid organs, especially in spleen and thymus. Both bursal and postbursal cells induced specific unresponsiveness to donor-line alloantigens. Bursal cell recipients accepted donor line skin grafts--and their graft-versus-host reactivity, as assayed by embryonal splenomegaly, and mixed lymphocyte reactivity against donor line alloantigens were significantly decreased. Despite differences in chimerism, a strong transplantation tolerance was readily induced with bursal stem cells and with postbursal cells. PMID- 2931869 TI - Suppression of antigraft immunity by preimmunization. IV. Persistence by long lived recirculating suppressor T cells. AB - Delayed-type hypersensitivity (DTH) against histocompatibility (H) antigens in mice, which normally arises after s.c. immunization, can be prevented by i.v. preimmunization with irradiated spleen cells carrying the relevant H antigens. We have previously shown that during the first week after i.v. preimmunization the nonresponsiveness is due to suppressor T lymphocytes. The induced state of nonresponsiveness, however, is long-lasting. In this study we investigated whether this long-lasting state of nonresponsiveness of DTH is associated with suppressor T lymphocytes or is caused by inactivation of the relevant clones of alloreactive T cells. This was done by parabiosis of nonresponsive and naive mice and by transfer of thoracic duct lymphocytes from nonresponsive mice, harvested at various intervals after the i.v. immunization. At a long interval after the i.v. immunization, the state of nonresponsiveness could still be transferred to syngeneic naive mice by parabiosis, as well as by transfer of thoracic duct lymphocytes. Selective elimination of the T cells from the latter by treatment with anti-Thy-1.2 plus complement prevented the transfer of the state of nonresponsiveness, indicating that suppressor T cells were involved. PMID- 2931870 TI - Improving recognition of onchocerciasis in primary care--1: Nonclassical symptoms. PMID- 2931871 TI - Christoffel Blindenmission, a Christian service to the blind and handicapped. PMID- 2931872 TI - [Swine serum increases hybridoma stability]. AB - Three hybridoma cell lines producing monoclonal antibodies to lambda phage were cultured for 9 months in Dulbecco's modified Eagl's medium supplemented with 10% fetal calf serum or with 5% swine serum. Under these conditions all the clones had the same proliferation rates and maximum population densities. The cultuvation in the medium with swine serum enhanced the stability of hybridomas: all clones retained the ability to produce antibodies throughout the experiment; one of the clones examined enhanced the activity by 10(3)-10(4) times. When the same three clones were cultured in the medium with the fetal calf serum, two of them lost their ability to produce antibodies 3-15 weeks after the beginning of the experiment. PMID- 2931873 TI - Determination of the hemodynamic factors which influence the carotid Doppler spectral broadening. AB - In the diagnosis of extracranial carotid arterial disease, quantitative measurements from the continuous wave (CW) Doppler spectrum have the potential for detecting stenoses and occlusions. The measurement of maximum peak Doppler frequency at the site of stenosis has been shown to detect severe, but not minor or moderate, stenoses. Diagnosis of minor or moderate stenoses may be possible by assessing the degree of flow disturbance beyond the stenosis. Such flow disturbances cause the Doppler spectrum at peak systole to be broadened, and it has been suggested that the measurement of spectral broadening may be of diagnostic value. This paper describes the results of an in vitro study aimed at determining the hemodynamic factors that influence the severity of the Doppler spectral broadening. The spectral broadening index (SBI) at peak systole, defined as SBI = 1 - Fmean/Fmax, was used to quantify the instantaneous spectrum. In a pulsatile flow in vitro model that produced spectral waveforms virtually identical to those recorded in the human carotid, we observed a direct linear relationship between SBI and the severity of stenosis, at least for those stenoses having greater than 40% cross-sectional area (R = 0.82 to 0.93). The SBI was found to be maximum when recorded immediately beyond the stenosis and returned to normal 4-5 cm downstream from the stenosis. The SBI was higher for nonsymmetrically shaped stenoses than for symmetrical stenoses for lesions greater than 60%, but not for stenoses less than 60%. In this model, the SBI recorded from both normal or abnormal waveforms was not affected by the flow rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2931874 TI - Quantitative estimation of spectral broadening for the diagnosis of carotid arterial disease: method and in vitro results. AB - For the quantitative assessment of carotid arterial disease using continuous wave Doppler ultrasound, the choice of an index to describe the degree of spectral broadening is important. It is shown that a spectral broadening index (SBI) given by 100(1 - fmean/fmax) and evaluated over a 25 msec period around peak systole is relatively insensitive to artifacts and has potential for achieving good clinical sensitivity. Furthermore, it can be implemented very simply on a microcomputer for on-line display. A description of a microcomputer based system, together with the results obtained using an in vitro flow model that closely approximates the carotid flow velocity waveform, are presented. Results relating the SBI to the degree of stenosis, recording site, and angle of insonation, are given. In addition, the results obtained with a commercial system that computes SBI based on the power spectrum, are presented for comparison. PMID- 2931875 TI - In vitro comparison of alternative methods for quantifying the severity of Doppler spectral broadening for the diagnosis of carotid arterial occlusive disease. AB - Quantitative analysis of continuous wave Doppler recordings is of clinical value in the noninvasive diagnosis of carotid arterial disease. Peak frequency measurements are useful and accurately detect severe stenoses but do not reliably diagnose minor or moderate stenoses because the measurement is dependent upon the probe to vessel angle, which cannot be measured accurately. Recent investigations have focused on efforts to overcome this limitation by quantifying the degree of spectral broadening that occurs as the result of flow disturbances downstream from a stenosis. In this study, an in vitro model was used to determine the optimum method for quantifying the instantaneous Doppler spectrum. The model generates blood flow velocity waveforms that are virtually identical to those found in the human internal carotid artery. Doppler recordings were made from normal tubes and distal to stenoses (39-87% cross-sectional area reduction). The spectra were quantified by the following angle-independent measurements: spectral broadening index and three standard statistical shape descriptors, namely the coefficients of variation, skewedness and kurtosis. Using this model, the results demonstrate an excellent relationship between the severity of the stenosis and each of spectral broadening index (r = 0.99), coefficient of variation (r = 0.96), and coefficient of skewedness (r = 0.99). The calculation of each of the measurements can be implemented quite easily, and a prospective trial is warranted to evaluate their clinical diagnostic accuracy. PMID- 2931876 TI - The detection of abnormal neonatal cerebral haemodynamics using principal component analysis of the Doppler ultrasound waveform. AB - Doppler ultrasound recordings were made from the anterior cerebral arteries of 40 normal full-term babies and 14 mature babies with intracranial pathology. The maximum velocity waveforms were extracted using spectral analysis and further analyzed using the Pourcelot resistance index method and the principal component method. Principal component analysis was found to be superior to the currently widely used resistance index method and may significantly enhance the value of Doppler ultrasound for detecting abnormal cerebral haemodynamics in neonates. PMID- 2931877 TI - Noninvasive aortic blood flow measurement using an intraesophageal probe. AB - The continuous measurement of cardiac output by the thermodilution technique is invasive, impractical and unpleasant for the patient. This paper describes the measurement of aortic blood flow with a specially designed intraesophageal echo Doppler probe. An A-scan unit allows the measurement of the diameter of the thoracic aorta and a continuous wave Doppler velocimeter is used for measurement of instantaneous blood flow velocity. In vitro experimental results as well as clinical studies are presented. PMID- 2931878 TI - Method for the measurement of the maximum Doppler frequency. AB - This paper describes a method for detection of the maximum Doppler frequency from a histogram of Doppler signals (HDS). The performance of the system is described, and its behavior in analysis of noise signals that have known lower and upper cut off frequencies is discussed. Experimental investigations show that the device correctly measures the maximum frequency envelope and can be useful in evaluating the maximum flow velocities in the blood circulation system. PMID- 2931879 TI - The use of Doppler ultrasonography for the evaluation of cerebral artery flow patterns in infants with congenital heart disease. AB - With the use of a two-dimensional range-gated pulsed-Doppler ultrasound system, Doppler examinations of the aorta and cerebral arteries were performed in 20 normal newborn infants and in 54 infants with various forms of congenital heart disease (i.e. patent ductus arteriosus, coarctation of the aorta, critical aortic stenosis, pulmonary atresia, truncus arteriosus). In the cerebral artery Doppler recordings of the normal infants, there was antegrade flow throughout systole and diastole. In the cerebral artery Doppler recordings of the infants with cardiac disease, various abnormal flow signals (i.e. retrograde or absent diastolic flow signals, increased systolic and diastolic flow signals, etc.) were found. Furthermore, the changes in the cerebral artery Doppler recordings were concomitant with changes in the aortic Doppler flow signals and the arterial blood pressure. Representative examples of the normal and abnormal Doppler flow patterns that were observed in the aorta and cerebral arteries are presented, and the mechanisms that could lead to these flow patterns are discussed. PMID- 2931880 TI - Noninvasive mapping of lower limb arterial lesions. AB - Thirty patients with peripheral arterial disease were evaluated using an ultrasonic duplex scanner. A total of 338 arterial segments from the level of the iliac to the popliteal artery were studied and compared with the results of arteriography read independently by two radiologists who were unaware of the results with the scanner. The results demonstrate that this method is not only suitable for clinical use but is as good as arteriography in defining both the location and extent of the arterial involvement. PMID- 2931881 TI - Detection of renal artery stenosis: experimental and clinical analysis of velocity waveforms. AB - Mass screening of hypertensive patients by a noninvasive method could uncover the 10% of those cases where renal artery stenosis is the primary etiology. Treatment by transluminal angioplasty or surgery could replace a long-term medical regimen. To investigate an ultrasonic technique, normal velocity waveforms were obtained from the abdominal aorta, celiac artery and renal arteries in seven mongrel dogs using a 5 MHz, continuous-wave Doppler detector. Renal artery pressure gradients, volume flow rates and velocity recordings were subsequently made during induced proximal renal artery stenoses. The ratio of peak renal artery frequency to peak aortic frequency was 88% sensitive to stenoses of greater than 20 mm Hg pressure gradient, while the renal artery systolic frequency window was 79% sensitive to the same obstructions. Ninety-five hypertensive and vascular surgical patients were examined using a 3 MHz duplex scanner with 175 of the 190 (92%) renal arteries adequately detected (clear signal with high diastolic component). Analysis of velocity waveforms based on peak frequency, proximal to distal peak frequency changes, evidence of flow disturbances and associated bruit were compared to contrast arteriograms in 84 vessels. Of the 76 (90%) arteries adequately examined by duplex scanning, 59 of 61 (97%) with 0-59% diameter reduction, 10 of 12 (83%) with 60-99% diameter reduction and 1 of 3 (33%) occlusions were correctly identified. Velocity waveform analysis can accurately detect renal artery stenosis and may prove effective in mass screening of hypertensive patients for renovascular disease. PMID- 2931882 TI - Spatial and temporal resolution of aortic Doppler blood velocity signals in normal human subjects. AB - We have used digital, microcomputer-based methods for the numerical analysis of pulsed, range-gated, ultrasonic Doppler blood velocity signals recorded with an axially aimed transducer from the ascending aorta of normal subjects. We investigated the spatial, temporal and amplitude resolution of our methods for recording and analysis, comparing aortic signals with test signals from a sine wave function generator. The spatial resolution of our system was found to be adequate in spite of the use of a relatively large sample volume. The temporal resolution was significantly influenced by the rate of change of velocity which affected the results of discrete fast Fourier transform analysis. The rate of increase in aortic blood velocity at the start of ejection was linear, following an initial jump in velocity. The amplitude resolution was affected by fluctuations in the amplitude of the Doppler signals. We conclude that our methods do not exaggerate the bluntness of the aortic velocity profile or the linearity of the increase in blood velocity at the start of left ventricular ejection. PMID- 2931883 TI - Doppler developments in the last quinquennium. AB - The major advances which have taken place during the last five years in the development of ultrasonic Doppler devices and methods of Doppler signal analysis are reviewed. The following aspects of instrumentation are considered: crossed beam Doppler systems, range measuring Doppler systems, duplex systems, flow mapping systems, transducers and measurements of system performance. Analytical methods are discussed in the following categories: waveform analysis, including the extraction of single-value waveforms and their applications to the diagnosis of vascular disease; spectral analysis, including the derivation of frequency spectra and their application in the study of blood flow; and volume flow estimation. It is concluded that it is likely to be in the study of the information in Doppler frequency spectra, two-dimensional real-time Doppler images and in the measurement of blood flow volume that most progress will be made. PMID- 2931884 TI - Measurement of blood flow by ultrasound: accuracy and sources of error. AB - Doppler ultrasound has now developed to the point where the rate of flow of blood in a given vessel can be measured with appropriate instrumentation. The theoretical basis of Doppler flow measurement is reviewed in this paper, with particular emphasis on the potential and actual sources of error. Three distinct approaches are identified, and the strengths and weaknesses of each discussed. The separate errors involved in estimating the vessel cross-sectional area, the angle of approach, and the Doppler shift are analyzed, together with the question of the uniformity of scattering from the blood. In vivo and in vitro tests of the accuracy obtained using a number of Doppler flow measuring instruments are then reviewed. It is concluded that the Doppler methods are capable of good absolute accuracy when suitably designed equipment is used in appropriate situations, with systematic errors of 6% of less. There are, however, considerable random errors, attributable primarily to errors in measuring the cross-sectional area and the angle of approach. Repeating the measurement of flow several times and averaging the results can reduce these random errors to an acceptable level. PMID- 2931886 TI - Duplex scanning of the thyroid. AB - High resolution ultrasound scanners are used to image nodular thyroid glands and in the study of thyroid malignancy. There are no specific ultrasonic characteristics of malignant lesions to distinguish them from benign conditions. Preliminary results using a Duplex ultrasound scanner shows that the detection of a high frequency Doppler-shift signal from the superior thyroid artery is indicative of an overactive thyroid. In a study of 23 consecutive patients who were being investigated for possible hyperthyroidism, 15 were found to have normal thyroid function and 8 to be overactive. The normals had a mean systolic peak frequency of 1.77 +/- 1.75 kHz, and the hyperthyroid group 4.08 +/- 1.5 kHz. This result is highly significant, having a p value less than 0.0002 (Mann Whitney U Test). In another 10 patients with solid lesions, one was diagnosed as follicular carcinoma. High frequency Doppler shift signals, similar to those found in carcinoma of the breast, were detected in the periphery of the lesion but were not found in nine cases of adenoma. Duplex scanning may assist in the investigation of hyperthyroidism and in the differential diagnosis of benign and malignant lesions. PMID- 2931885 TI - Duplex Doppler scanning in the pelvis and abdomen. AB - New Doppler applications of Doppler ultrasound are becoming apparent in the abdomen and pelvis. Interpretation of the Doppler signals may be qualitative, semiqualitative or quantitative. Normal time-velocity spectra in major vessels of the abdomen and pelvis are described. In the diagnosis in pathology, Doppler can be used to document the presence and direction of flow in the portal venous system. In can aid in the identification of an abnormal structure. It provides much of the perfusion data required before and subsequent to liver transplantation. In normotopic renal vessels, it can exclude thrombosis and stenoses in many patients. In renal transplants, it is invaluable as a rapid means to assess patency, renal artery stenosis and vascular rejection, thereby extending the role of conventional imaging. Early studies in the pelvis have demonstrated changes in the ovarian signals associated with ovulation. Doppler can be used to assess bowel viability, impotence due to vascular insufficiency and to exclude testicular torsion. Finally, blood flow in malignant tumors has been demonstrated to give rise to Doppler signals with characteristic qualities, and this technique awaits thorough investigation in the abdomen. PMID- 2931887 TI - Accurate diagnosis of detrusor areflexia using combined uroflowmetry and abdominal wall electromyography. AB - Twenty-three patients who previously demonstrated no detrusor contraction during cystometry were evaluated using a combined uroflowmetry and abdominal wall electromyography. Ten patients voided without abdominal straining (normal detrusor reflexia), 11 could not void without abdominal straining (detrusor areflexia, detrusor weakness, or bladder outlet obstruction), and 2 had equivocal findings with the method. PMID- 2931888 TI - [Immunological aspects of laryngeal cancer]. PMID- 2931889 TI - [The surgeons of the Leningrad Medical Institute for Postgraduate Training of Physicians in the past 100 years]. AB - The article presents data concerning the surgeons who worked at the Leningrad Medical Institute for Postgraduate Training and achievements of surgical departments during 100 years of existence of the institute. PMID- 2931890 TI - [Various current problems of organization of emergency abdominal surgery]. PMID- 2931891 TI - [Role of mobile cycles of advanced training of surgeons in the development of specialized surgical services]. PMID- 2931892 TI - [Current problems and achievements of cardiosurgery at the Leningrad Medical Institute for Postgraduate Training of Physicians]. AB - The authors analyse the experience with the surgical treatment of about 3000 patients with different forms of cardiac pathology and general lethality in 4,1% of cases. Favorable results were obtained following operations in children of the first three years of life with the open arterial duct, in 4 to 6-year-old children with coarctation of the aorta. The authors show expediency of correction of septal defects before severe disturbances of hemodynamics could develop. The closed method of correction is indicated in non-complicated forms of mitral stenosis. Patients with complicated forms of mitral stenosis, mitral insufficiency should be operated upon under conditions of artificial blood circulation. PMID- 2931893 TI - [Achievements and prospects of the development of surgical stomatology at the Leningrad Medical Institute for Postgraduate Training of Physicians]. AB - The author makes an analysis of the achievements of the Soviet surgical stomatology in such main problems as injury of the maxillofacial area, inflammatory diseases, developmental defects. The role of scientists of the Department of Surgical Stomatology of the Leningrad Medical Institute for Postgraduate Training is shown. PMID- 2931894 TI - [The role of the Leningrad Medical Institute for Postgraduate Training of Physicians in the training of surgical specialists]. AB - The first in the world Medical Institute for Postgraduate Training was founded in 1885. For the period of its existence more than 100 thousand surgeons and physicians of adjacent specialties could improve their qualification. PMID- 2931896 TI - Laparoscopy in small animal medicine. AB - Laparoscopy is described as a safe, simple, and relatively non-invasive diagnostic technique for the visualization of abdominal organs. The instruments required, the procedure of laparoscopy, and indications and contra-indications are described. The advantages of laparoscopy above laparotomy are discussed. PMID- 2931895 TI - Ultrastructural ocular lesions of 6-aminonicotinamide toxicosis in rabbits. AB - 6-Aminonicotinamide, given by intraperitoneal injection to male and female Dutch belted rabbits, produced swelling and vacuolation of ciliary and iridal epithelium plus vacuolation of the retinal pigment epithelial and outer plexiform layers of the retina. By transmission electron microscopy, inner and outer ciliary epithelial cells and inner iridal epithelial cells contained numerous coalescing, membrane-bound vacuoles of the cytocavitary network. These vacuoles were viewed as numerous interconnecting, intracytoplasmic cavities in scanning electron micrographs. Swelling of vacuolated epithelial cells and the presence of fibrin and proteinaceous fluid in the ciliary stroma resulted in thickening of the anterior ciliary processes with the formation of surface alterations detectable by scanning electron microscopy. In transmission electron micrographs the vacuoles in the retinal pigment epithelium were large, electron-lucent spaces and the vacuoles in the outer plexiform layer of the retina appeared to be intracytoplasmic spaces in axons of photoreceptor cells. Distention of cytocavitary structures has been reported in glial cells of animals given 6 aminonicotinamide and this change was apparently due to alterations in ion and water movement across cellular membranes that resulted in intracellular edema. PMID- 2931898 TI - [Medical services in the 50th Army during the capture of Konigsberg]. PMID- 2931897 TI - [The effect of chronic renal insufficiency and regular dialysis treatment on the heart]. PMID- 2931899 TI - [Organization of the treatment of wounded and sick in evacuation hospitals in the Southern Ural region]. PMID- 2931900 TI - [Isolation and properties of acylplasmin]. AB - Plasmin, free of an activator, was obtained after activation of the highly purified human plasminogen by means of trypsin immobilized on Sepharose 4B and after removal of the enzyme from the system. Plasmin was acylated at the active centre using p-amidinophenyl ester of p'-anisic acid to produce the fibrinolytic agent causing a long-term effect. Inactive acyl plasmin was deacylated with the constant rate k3 = 3.10(-4) c-1 (r1/2 = 40 min) at pH 7.4 and 37 degrees. Preliminary studies of the anisoyl-plasmin effect on the system of fibrinolysis in rats showed that in the absence of fibrin clot the fibrinolytic activity was not increased immediately in the euglobulin fraction of blood but after 30 min in result of deacylation of the acyl-enzyme administered into circulation. PMID- 2931901 TI - [Chemotherapy of prostatic cancer]. PMID- 2931902 TI - [Experience with the work of centralized cytologic laboratories in the Byelorussian S.S.R]. AB - The experience of amalgamated cytological laboratories in the Byelorussian SSR with mass screening for non-tumorous lesions and carcinoma of cervix uteri is discussed. The high predictive value of cytological procedures of detection of dysplasia and early cervical cancer was demonstrated. It is stressed that cases revealing moderate or pronounced dysplasia should undergo an all-round examination. PMID- 2931903 TI - [Detection of hepatitis B viral markers (HBsAg and anti-HBs) in medical personnel]. AB - The risk of infection with viral hepatitis B (HB) in medical personnel of various professions was determined. Differences in the detection of hepatitis B virus markers in medical workers of Moscow and the town of Kzyl-Orda were demonstrated. The maximum number of persons with anti-HBs were found among laboratory personnel (30.8%), physicians (21.5%), hospital attendants (18.8%). The level of detected HBV markers correlated with the degree of contacts with blood. The rate of anti HBs detection increased with the duration of work in the public health system and reached the maximum levels in the group of persons with a work record of 15-19 years. Comparative evaluation of counter-current immunoelectrophoresis, indirect hemagglutination, and ELISA methods for the detection of HBsAg was made. PMID- 2931904 TI - [Experiences with stomatologic care of brain damaged educable children]. PMID- 2931905 TI - [Subjective assessment of personal handicaps of medium grade and severely disabled patients]. PMID- 2931906 TI - [Animal experiment and biopsy studies on the cause, manifestations and diagnostic relevance of perifascicular muscle fiber atrophy]. AB - On the basis of previous (n = 23) and current muscle biopsies (n = 25) as well as five animal-experimental investigations, the paper deals with the cause and the manifestation of perifascicular muscle-fiber atrophy. A deteriorated trophic situation of the subfascial or marginal muscle fibers in patients suffering from immunocomplex vasculopathies in connection with a reduced supply of blood to the muscles is seen as the cause of the areactive weight loss (atrophy). This is accompanied by a considerably reduced capillary supply of blood to the muscle fibers. Even in normal conditions, the portion of collateral vessels and capillaries is lower in the subfascial region than in the center of the fascicle. When the blood supply is disturbed, the marginal fibers are in a trophic situation worse than that of the central muscle fibers. They become atrophied. In responsive patients, the muscle fibers regenerate and recapillarize during the convalescence period. This can be shown histochemically by means of the alkaline phosphatase reaction. The extent of perifascicular musclefiber atrophy can be fixed in quantitative terms by the method of Baumli and Mumenthaler. Where a second biopsy is indicated, results can be obtained regarding the changes in the perifascicular atrophy as a consequence of the therapy provided. PMID- 2931907 TI - [Thrombolytic treatment of peripheral arterial circulatory disorders with streptokinase]. AB - The purpose of these investigations is to refer to the possibility of the reconstructive treatment of arterial obstructions by means of streptokinase. New application methods improved the chances of success of fibrinolysis. They run about 50%. The local application of smaller doses of streptokinase confines the contraindications to a certain extent. Obstruction in the pelvic area which are not older than three months and such ones in the femoropopliteal part up to 6 weeks are to be regarded as indication to the fibrinolysis. In the care of patients with arterial obstructive diseases importance should, therefore, be attached to the fact that thrombotic shifts should be recognized in time an the possibility of a fibrinolytic therapy is tested within the periods mentioned. PMID- 2931908 TI - [Prenatal diagnosis: gastroschisis--pediatric surgical considerations and a report of 13 cases]. AB - The gastroschisis is a congenital defect of the abdominal wall without other abnormalities and can be diagnosed by ultrasonography before 20 weeks of gestation. The management of these cases requires the cooperation of the obstetric and pediatric clinician in respect of an elective abortion. As a result of the advances in pediatric surgery and neonatal intensive care the treatment of the gastroschisis is possible and the prognosis of these children is very good. In the years 1978-1983 the primary closure of the abdominal wall defect was performed in 13 newborns. Whereas one child died due to intrauterin complications (volvolus and intestinal gangren) the 12 remaining patients could be operated successfully. We are of opinion that termination of pregnancy is indicated no longer in cases of gastroschisis. PMID- 2931910 TI - [Use and experiences with collagen in the treatment of folds and scars]. AB - We report on the use of xenogenous collagen (Zyderm) in treating the aging skin, scars and atrophic states. Indications and contraindications as well as the technical approach with regard to the different disorders will be discussed. PMID- 2931909 TI - [Chemiluminescence measurement in AIDS, lymphadenopathy and hemophilia patients]. AB - In order to reveal the activity of polymorphonuclear neutrophil leukocytes (PMNL) representing the first step of defence against infections, measurements of chemiluminescence (CL) were performed in patients suffering from acquired immune deficiency syndrome (AIDS), lymphadenopathy, or hemophilia. In comparison with healthy controls, AIDS patients revealed significant reduction (about 50 per cent) of phagocytic, i.e. CL activity of neutrophils, which had been induced by Zymosan. Only part of the patients suffering from lymphadenopathy answered with decreased granulocyte activity on the application of Zymosan. If concanavalin A was used as stimulant of metabolic activity of PMNL-independently of phagocytosis again AIDS and some of the lymphadenopathy patients showed a markedly reduced neutrophil response. In conclusion it should be stated that there is some evidence for at least two defects of cellular immunity associated with AIDS and to some extent, with AIDS-endangered homosexuals suffering from lymphadenopathy: first the defect of PMNL to answer to concanavalin A with increased metabolic activity, and secondly the defect of PMNL to start phagocytosis induced by Zymosan with a subsequent release of oxygen radicals which are measurable as chemiluminescence. The appraisal of granulocyte activity by means of measurements of chemiluminescence might become an additional criterion for AIDS diagnostics. PMID- 2931911 TI - [Improved occlusion tolerance time by continuous coronary perfusion with a modified Gruntzig coronary angioplasty catheter]. AB - We evaluated the modified Gruntzig coronary angioplasty catheter, which allows for continuous antegrade coronary perfusion during balloon occlusion without the use of an external pump. During in vitro tests the flow rates for effective pressure differences between aorta and distal coronary vessel in the range between 25 and 100 mm Hg were determined. During in vivo tests in 10 dogs the effect of balloon occlusion with continuous perfusion (OM) was compared with conventional occlusion without perfusion (OC). The occlusion tolerance time (OTZ) as determined by the appearance of unequivocal signs of ischemia in the ECG, was 486 +/- 77 s for OM versus 256 +/- 82 s for OC with a relative, individual increase of 191 +/- 54% (p less than 0.01, data are given +/- SEM). Observed ST elevation was less with OM than with OC (0.22 +/- 0.05 versus 0.33 +/- 0.06, p less than 0.05). Occlusion related pressure difference between aorta and occluded coronary vessel was less with OM than with OC (31 +/- 8 mm Hg versus 40 +/- 10 mm Hg, p = 0.05). In selected cases such a prolongation of the intracoronary balloon occlusion time may represent a distinct advantage. PMID- 2931912 TI - [Frequency spectrum analysis of Doppler ultrasound signals in extracranial carotid artery lesions]. PMID- 2931913 TI - [Current problems in occupational diseases of the skin]. PMID- 2931915 TI - [Familial genetic research on the clinical picture in periodontal atrophy]. PMID- 2931914 TI - [Time-dependent flow behavior and fibrinogen content of synovial fluid]. AB - Normal bovine synovial fluid and synovial effusions in human non-inflammatory joint diseases do not show any decrease of viscosity for a long period of time during imposed shear loading, as is required for thixotropy. This observation is based on two different methods of measurement; the "hysteresis loop" method and the recording of the shear stress-time curve. Inflammatory synovial fluids- particularly from patients with rheumatoid arthritis and a high concentration of fibrinogen--form a visible gel after 6 to 20 hours of rest. Those gels show a hysteresis loop typical for thixotropy and a decrease of viscosity with the duration of shear loading. Due to the shearing in the rheometer precipitation occurs and fibrin clots appear. The appearance of fibrin clots induced by mechanical shear loading not known until now, can be discussed with regard to its possible participation in the symptom of morning stiffness, in the formation of rice bodies and in the destruction of joint cartilage in rheumatoid arthritis. PMID- 2931916 TI - [Therapeutic results in periodontal diseases with a primary immune defect and diabetes mellitus]. PMID- 2931917 TI - [Chemical and electrochemical effects of electrolytic polishing on model cobalt chromium cast alloys]. PMID- 2931918 TI - [Squamous cell carcinoma of the oral cavity with special reference to xenogeneic transplantation into nude mice]. PMID- 2931919 TI - [Epidemiology of facial bone fractures from 1945 to 1980]. PMID- 2931920 TI - [Effect of the surgical procedure in the closure of unilateral cleft lips on the shape and position of the external nose]. PMID- 2931921 TI - [Treatment of chewing, swallowing and speech defects in handicapped children with Castillo-Morales orofacial regulator therapy: advice for pediatricians and dentists]. PMID- 2931922 TI - [Chronic pancreatitis as a predisposing factor in the development of pancreatic cancer. Histological and histochemical studies]. AB - The frequency of hyperplasia, squamous metaplasia and dysplasia were examined in glandular tissue from 20 pancreatic specimens resected due to chronic inflammation. Hyperplasia of the epithelium of large pancreatic ducts with formation of papillomatous outgrowths was present in 6 cases. Epithelial hyperplasia of small ducts occurred in 10 cases. Dysplasia and squamous metaplasia of the epithelium of ducts, hypertrophy, hyperplasia and dysplasia of acinar cells were found in 7 cases. In 10 pancreatic specimens hypertrophy and hyperplasia of cells of the islets of Langerhans were noted. Increased histochemical reactions to dehydrogenases and proteinic thiol groups were present in epithelial cells which demonstrated hypertrophy, hyperplasia, metaplasia or dysplasia. Diminution of the PAS reaction to neutral glycoproteins and intensification of the reaction to acid glycoproteins were also noted in the ductal epithelium. The results obtained suggest that chronic inflammation of the pancreas should be clinically regarded as predisposing to the development of pancreatic cancer. PMID- 2931923 TI - [Intra-alveolar stabilizing posts]. PMID- 2931924 TI - [Bonded bridges: clinical phase. The Duralingual technic]. PMID- 2931925 TI - [Work-up of dental ceramics using casting technics]. PMID- 2931926 TI - [Gnotobiotic studies on SPF mice in relation to a study of tumor development in the colon after cholecystectomy]. AB - The relation between cholecystectomy and colon carcinogenesis has not been fully elucidated. As bacteria may be involved in the carcinogenic process, we investigated the effect of cholecystectomy and dimethylhydrazine (DMH) administration to SPF NMRI mice with regard to tumour genesis and bacterial colonisation of the intestine. It results from this study that cholecystectomy does not influence tumour genesis and that 6-7 months post operationem and DMH administration tumours and bacteria originally not found in the animals develop: clostridia, eubacteria spec. which cannot be differentiated and E. lentum. Theses changes appear in group II of mice (laparotomy and DMH) and group III (cholecystectomy and DMH), but not in group I (controls). From the results of this study we cannot conclude whether the tumours or the new bacteria appeared first. Biochemical investigations of C. innocuum, C. paraputrificum and C. tertium indicated that these bacteria metabolised bile acids by a specific metabolic step only but not produced carcinogenic substances themselves. If bacteria are involved in tumorgenesis, different species may be involved producing a carcinogenic environment by metabolic chain reactions. We know of such a bacterial collaboration in anaerobic infections. PMID- 2931928 TI - [Correlation between the virulence of streptococci for mice and their IgG FcR activity in in vivo experiments]. AB - The immunological analysis of 24 spontaneous Strr, Rifr and Kanr mutants of streptococcal strain IP, highly virulent for mice and capable of binding polyclonal human IgG (IgG FcR+), was made. The characteristic feature of all these mutants was decreased virulence, restored after their passage in vivo. 23 mutants were capable of binding polyclonal IgG; one Strr mutant had no such capacity, but acquired it, together with an increase in virulence, after its passage in vivo. When stored in meat-peptone agar without antibiotics, 5 out of 10 Strr mutants lost their capacity for binding polyclonal human IgG. After passage in vivo they regained this property simultaneously with virulence. PMID- 2931927 TI - Comparative determination of minimal inhibitory and bactericidal concentrations of ciprofloxacin, cefotaxime and HR 810 for gram-negative bacteria either sensitive or resistant to ureidopenicillins and/or gentamicin. AB - The minimal inhibitory (MIC) and minimal bactericidal (MBC) concentrations of ciprofloxacin were compared with those of the cephalosporins HR 810 and cefotaxime in 250 strains from 10 species of Gram-negative bacteria with sensitivity or resistance to gentamicin and/or piperacillin. Ciprofloxacin had an inhibitory activity higher than, or practically equal to the best of the two cephalosporins. The MBC of ciprofloxacin was more often less than or equal to twice the MIC than with the beta-lactam antibiotics. Parallel resistance was found with pipemidic acid as representative of DNA-gyrase inhibitors. No direct parallel resistance was observed with resistance to gentamicin, piperacillin or cefotaxime. PMID- 2931929 TI - [50th anniversary of the Department of Neurosurgery of the Leningrad S. M. Kirov Leningrad Institute for Postgraduate Medical Training]. PMID- 2931930 TI - Pain threshold elevation by electrostimulation of sensitive fibres of middle class diameter. PMID- 2931931 TI - [Immersion diuresis]. PMID- 2931932 TI - [Various treatment modalities in pain]. PMID- 2931934 TI - [The use of T.E.N.S. in pain control]. PMID- 2931933 TI - [Evaluation of the diagnostic value of muscle testing and of the EMG in the lumbosciatic syndrome]. PMID- 2931935 TI - [Pathology of the talus in sports traumatology: osteochondritis dissecans of the astragalus]. PMID- 2931936 TI - [Baths and their impact on the hypothalamo-hypophyseal axis]. PMID- 2931937 TI - Endoscopic sclerotherapy v. conservative management of bleeding oesophageal varices. A 5-year prospective controlled trial of emergency and long-term treatment. AB - A comparative trial was made of conservative therapy (balloon tamponade and/or vasopression infusion) alone (control group) or with addition of acute and serial endoscopic injection sclerotherapy (ST group). The 107 unselected patients, mainly with alcoholic cirrhosis, were randomly allocated to these groups, which were comparable as regards Child's grading and clinical and laboratory findings. For emergency ST a fibreoptic endoscope and Williams sheath were used. In initial control of index bleed and hospital mortality the two groups did not differ significantly. The median follow-up was 15 and 28 months (minimum 1 year). Supplementary ST (mainly out-patient) gave variceal eradication in 34 of 41 patients, with most failures in persistent alcoholics. A calculated risk factor for rebleeds was 3.6 times higher in the controls than in the ST group. Mortality rate showed no intergroup difference. The cause of death mainly was variceal bleeding in the controls, but not in the ST group. Major complications of treatment occurred in c. 15% of all patients. PMID- 2931938 TI - Hand eczema and long-term prognosis in atopic dermatitis. AB - A follow-up study of 1177 adult patients who had had atopic dermatitis (AD) (Groups 1 and 2) or respiratory allergy (Group 3) in childhood is reported. Patients who had had AD in childhood had received in-patient (Group 1) or out patient treatment (Group 2) for their dermatitis. 183 patients in Group 1 and 162 in Group 2 were examined clinically. Further, 445 patients who had recently been treated for hand eczema at a department for occupational dermatoses were studied (Group 5). A group of 199 people who had no personal or family history of atopy served as controls (Group 4). The essential findings were as follows: The healing rate was lower (38%) in patients with severe (Group 1) than in those with moderate (60%) childhood dermatitis (Group 2). Although the healing rate was comparatively low in both groups, persistent eczema was in most cases of mild degree. The commonest localization of persistent dermatitis was the hands. The AD had developed earlier in patients who had had severe childhood dermatitis than in those whose childhood AD was moderate. Severe childhood AD was also associated with a significantly higher frequency of family history of atopy and associated respiratory allergy. The inheritance pattern was specific for the different types of atopic disease. A family history of AD was significantly commoner in people with AD than in people with respiratory allergy, and, conversely, people with a family history of respiratory allergy had developed asthma or allergic rhinitis rather than AD. The serum IgE level was raised in 45% and 26% of the clinically examined individuals in Groups 1 and 2, respectively. A comparatively large proportion of patients with persistent or recurrent dermatitis had normal IgE values. There was a strong correlation between the extent of persistent dermatitis and serum IgE levels. It is concluded that the serum IgE cannot be used to establish the diagnosis of atopic dermatitis. The number of contact sensitized people was greater in Group 2 (23%) than in Group 1 (17%). Occurrence of contact sensitivity, which was demonstrable in a total of 20% of the patch tested individuals from Groups 1 and 2, was not correlated to prevalence of healing at the time of examination. Fragrance-mix and balsam of Peru were the commonest contact sensitizers. People with a history of AD showed a higher incidence of recurrent (greater than 5 episodes per year) cold sores, upper respiratory infection, and herpes zoster than non-atopic controls.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2931939 TI - Valproate: an updated review. AB - Valproate in all its aspects is comprehensively surveyed. Previous reviews covering various aspects such as mechanism of action, clinical pharmacology, clinical efficacy in epilepsy, febrile convulsions and other neurological disorders, side effects, teratogenicity and intoxications are discussed and updated (161 references). PMID- 2931940 TI - Abnormalities of T-lymphocyte subsets in epileptic patients. AB - This study concerns the distribution of T-cell subsets as determined by specific monoclonal antibodies in 50 individuals with complex partial seizures (31) and primary generalized tonic-clonic seizures (19), and in 30 healthy controls. The epileptic group had significantly fewer circulating T4 "helper" lymphocytes and significantly greater number of T8 "suppressor" lymphocytes than the controls. The T4/T8 ratio was consistently significantly lower in the epileptic group. There was no relation between lymphocyte subsets or T4/T8 ratio and antiepileptic medication. The results suggest a derangement of cell-mediated immunity in individuals with epilepsy. PMID- 2931943 TI - Immunological profile in children with minimal change nephrotic syndrome. AB - Peripheral blood from patients with active stage of minimal change nephrotic syndrome (MCNS) was examined for concanavalin A (ConA)-inducible suppressor T cell activity, proliferative response to phytohemagglutinin (PHA) and in the autologous (AMLR) and allogeneic (MLR) mixed lymphocyte reaction, proportions of T cells with receptors for IgM (Tu) or IgG (T gamma) and the levels of serum immunoglobulin M, G and A. Six of 9 patients with MCNS studies showed deficiency of ConA-induced suppressor cell activity. In the AMLR, only one of 9 patients with MCNS demonstrated depressed proliferative response (p less than 0.05). In the allogeneic MLR, T cells from 5 of 9 patients with MCNS demonstrated poor proliferative response when stimulated with normal control non-T cells. Five of 9 patients with MCNS had depressed proliferative response to PHA. The proportion of total T cells, Tu cells and T gamma cells in the patient group were comparable to healthy control group. Serum IgG was significantly decreased in 7 of 11 patients. This study demonstrates multiple immunological abnormalities in patients with MCNS that might play a role in its pathogenesis. PMID- 2931941 TI - GM2 gangliosidosis in a Japanese spaniel. AB - A storage disease in a 2-year-old Japanese Spaniel resembled a GM2 gangliosidosis previously identified in a now extinct line of German Shorthaired Pointers. Despite a later appearance of signs in the Japanese Spaniel, the distribution, staining, and ultrastructure of the stored material were similar in the two breeds. Golgi studies of cerebral cortical neurons revealed the formation of spiny and aspiny enlargements at the axon hillock region (meganeurites) and the growth of secondary neurites from this region. As in the German Shorthaired Pointer model, there was massive storage of GM2 ganglioside as well as a seemingly paradoxical increase in total beta-hexosaminidase activity measured in vitro. PMID- 2931942 TI - Immunoreactive SOD-1 in amniotic fluid, amniotic cells and fibroblasts from trisomy 21 fetus. AB - Copper superoxide dismutase (Cu-SOD or SOD-1) was measured by radioimmunoassay (RIA) in amniotic cells and fluid as well as in fetal trisomy 21 fibroblasts. The significant increase of the SOD-1 activity observed in amniotic cells and fetal trisomy 21 fibroblasts demonstrates the early physiopathogenic expression of the supernumerary chromosome 21 in affected patients. PMID- 2931944 TI - Impaired in vivo platelet reactivity in infantile autism. PMID- 2931945 TI - Release of fibronectin, sulfated glycosaminoglycans and beta-hexosaminidase from injured smooth muscle cells and fibroblasts in culture--possible transferable effects on new cultures. AB - The effect of injury to the bovine arterial smooth muscle cell in vitro was studied. Injury was caused by dimethylsulphoxide-soluble particles from cigarette smoke. The release of fibronectin was studied with human skin fibroblasts, but all other experiments on bovine myocytes. Fibronectin release was increased from injured cells, while that of sulfated glycosaminoglycans was decreased. These changes in release were evident already during the first hour after injury, while the increased release of the lysosomal enzyme beta-hexosaminidase was manifest 1 24 hours after injury, but not during the first hour. Conditioned medium from injured cells was toxic to new cultures. This toxicity could be prevented by including the protease inhibitor alpha 1-antitrypsin to the cultures exposed to smoke particles. When alpha 1-antitrypsin was added first after the cells had been exposed to the smoke particles it was without effect. The free radical scavenger vitamin E was without effect. Cell detachment was a good index of cell death after exposure to cigarette smoke particles, as judged from the simultaneous measurement of DNA content and trypan blue uptake. During the period 24 hours after the toxic influence of cigarette smoke particles on original cultures, or 24 hours after the action of conditioned medium on new cultures, the injured cells revealed an augmented DNA synthesis compared to controls. The injured cells were, however, less responsive to growth-stimulating activity from platelets. PMID- 2931946 TI - Structural adaptation of the rat left ventricle in response to changes in pressure and volume loads. AB - Female Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were used to explore the structural changes of cardiac dimensions in connection with a sustained hyperkinetic circulation, as induced by pregnancy or thyroxine administration. Cardiac design was assessed by recordings of the diastolic left ventricular pressure-volume relationships in isolated arrested hearts. Left ventricular weight: body weight and end-diastolic volume (EDV) for given end diastolic pressures (EDP), were both increased about 50% in control SHR, with a marginal reduction of the wall:lumen ratio (w:ri) compared with control WKY. During the hyperkinetic circulatory states of pregnancy and hyperthyroidism, EDV was in WKY increased about 30% and 50%, respectively, with concomitant w:ri reductions. In SHR pregnancy did not significantly alter left ventricular dimensions, whereas EDV was increased by about 20% in hyperthyroid SHR. Thus, the rat left ventricle can, within 3 weeks, markedly alter not only the wall mass but also, and independently, the luminal design in response to different haemodynamic interventions. Early established SHR hypertension is characterized mainly by eccentric left ventricular hypertrophy, despite the elevated arterial pressure. Volume overloads in WKY due to pregnancy or hyperthyroidism can induce marked structural widening of the left ventricle. In SHR these structural luminal changes were only minor, perhaps because considerable eccentric hypertrophy is already present. Such a structural cardiac enlargement may allow delivery of an increased stroke volume for a given myocardial fibre shortening. PMID- 2931947 TI - Profiles of antidepressant activity with the Montgomery-Asberg Depression Rating Scale. AB - The Montgomery and Asberg Depression Rating Scale (MADRS) is a 10 item severity scale constructed to be sensitive to change with treatment. It was designed to be sensitive for individual items and is therefore useful for measuring differential profiles of action. The MADRS profiles of activity were examined in a six-week double-blind comparative group study of depressed patients treated with mianserin or zimeldine. Three of the ten items on the MADRS showed individual significant advantages for mianserin, reduced sleep (weeks 1 and 3), concentration difficulties (week 1), and reduced appetite (week 3). These findings are in agreement with earlier reports of poor sleep and gastrointestinal upset associated with the 5-HT uptake inhibitor zimeldine. The selective improvement in concentration difficulties and in the other items support the view that mianserin is particularly useful in alleviating the anxiety associated with depression. The sedative effect of mianserin did not appear to interfere with concentration. There were significant improvements in the mianserin-treated group at 1, 2, 3, and 4 weeks for the MADRS, Hamilton Depression Rating Scale and Clinicians Global Impression scale. There was no significant advantage for mianserin at 5 and 6 weeks. The differential clinical effects were apparent early in the study but any selectivity of action appeared to be overwhelmed by the general antidepressant effect later in treatment. PMID- 2931948 TI - Effect of tricyclic drugs on mitochondrial membrane. AB - The effects of tricyclic drugs (clomipramine, imipramine, chlorpromazine and promethazine) on isolated liver mitochondria of rats were examined. All the drugs tested accelerated state 4 respiration. Their stimulative potency at concentrations below 100 microM was in the order of chlorpromazine greater than clomipramine greater than imipramine, promethazine. On state 3 respiration, the chlorine containing drugs had an inhibitive effect at high concentrations, while the other drugs seemed to have a slightly stimulative effect. These drugs stimulated latent ATPase activity of mitochondria. Clomipramine and chlorpromazine inhibited 2, 4-dinitrophenol-stimulated ATPase activity in a dose dependent fashion. Imipramine also inhibited 2, 4-dinitrophenol-stimulated ATPase activity at high concentrations. Promethazine, however, had almost no effect. All the drugs induced potassium release from mitochondrial vesicles, and their potency was in the order of clomipramine greater than chlorpromazine greater than imipramine greater than promethazine. These results suggest that clomipramine, imipramine, chlorpromazine and promethazine cause impediments in both mitochondrial respiration and ion compartmentation, and that the chlorine containing drugs are more toxic than others on the functions of the mitochondrial membrane. PMID- 2931949 TI - [The metabolic aspects of alcoholism]. PMID- 2931950 TI - Demonstration of circulating immune complexes by the indirect leucocyte phagocytosis test in chronic inflammatory bowel disease. Relation to results of a standard complement consumption assay. AB - Circulating immune complexes were studied in untreated Crohn's disease (CD) and ulcerative colitis (UC) by leucocyte phagocytosis. Neutrophils from normal donors took up large immunoglobulin-containing inclusions from 14 of 15 CD sera, 3 of 15 UC sera (p less than 0.002) and from none of 15 reference sera from healthy volunteers (p less than 0.002). In contrast, inclusions could not be demonstrated on direct microscopic investigation. Our study confirms the presence of circulating immune complexes in Crohn's disease. Predominance of IgG-containing complexes in this condition is consistent with a mucosal origin. Discrepant results obtained by direct examination and by incubation of sera from patients with normal test neutrophils suggest a defective immune complex phagocytosis in CD. In consistency with this possibility, control experiments revealed a markedly decreased complex uptake by neutrophils of CD patients in vitro. PMID- 2931951 TI - Human lymphocyte subpopulations in lymphadenopathies in homosexual men. PMID- 2931952 TI - Antigen/antibody retention by follicular dendritic cells (FDC). PMID- 2931953 TI - Precursors of T-cell mitogen reactive cells and their suppressors in the mouse fetal liver. PMID- 2931954 TI - Studies on the role of the thymus in the selection and clonal expansion of T-cell precursors. PMID- 2931955 TI - T-cells and T-cells subsets in rat bronchus associated lymphoid tissue (BALT) in situ and in suspension. PMID- 2931956 TI - Antibody responses to T-dependent antigens: contributions of dendritic cells and helper T lymphocytes. AB - Dendritic cells (DC) are important accessory cells for T-dependent antibody formation. Other leukocytes -- such as macrophages and B cells -- do not independently initiate antibody responses. DC induce the two principal functions of helper T cells, i.e., direct activation of small, antigen-specific B cells, and release of B cell stimulating factors. These two helper functions can operate in tandem during the 1 degree response to hapten-carrier conjugates. Once the helper cell is sensitized in concert with DC, it interacts directly with B cells apparently in the absence of DC. These functions of helper cells all occur in discrete aggregates which contain DC and the appropriate responding lymphocytes. The DC/lymphocyte aggregates likely represent the appropriate structural unit for the study of cell-cell interactions during antibody responses. PMID- 2931957 TI - T-lymphocytes in rat lymphoid follicles are a subset of T helper cells. PMID- 2931958 TI - Maternal autoimmune disease influences self-tolerance in offspring. PMID- 2931959 TI - The long-lasting state of specific nonresponsiveness induced by intravenous immunization with alloantigens is due to the generation of recirculating suppressor T cells. AB - We investigated whether the long-lasting state of nonresponsiveness that is induced by intravenous immunization with alloantigens is mediated by suppressor T cells, or is caused by inactivation or deletion of the relevant alloreactive T cell clones. The data from parabiosis and thoracic duct drainage experiments suggest that the state of nonresponsiveness depends on recirculating non proliferating Ts memory cells. PMID- 2931960 TI - Graft versus host reaction in the rat: effect of cyclosporin A and cyclophosphamide on lymphocyte subsets involved in GvHR. PMID- 2931961 TI - Lymphokine production by T lymphocytes isolated from murine small intestinal epithelium. PMID- 2931962 TI - Therapeutic potential of monoclonal antibodies to the leucocyte common antigen. PMID- 2931963 TI - Nodular lymphocyte predominance type of Hodgkin's disease is a B cell lymphoma. PMID- 2931964 TI - The effect of ketanserin, a 5-HT2-receptor antagonist, on 5-hydroxytryptamine induced irreversible platelet aggregation in patients with cardiovascular diseases. AB - Platelet aggregation in response to 5-hydroxytryptamine was investigated in 40 normal subjects, in 45 patients with acute myocardial infarction, and in 65 patients with peripheral arterial obstructive disease. It was found that of the 110 patients with cardiovascular disease, 40% had a biphasic irreversible platelet aggregation, whereas this phenomenon occurred in only 7.5% of the normal population. A double-blind placebo-controlled study further showed that a subacute treatment with ketanserin, a selective 5-HT2-receptor antagonist both on platelets and on vascular tissue, efficiently abolished the irreversible platelet aggregation in patients hyperreactive to 5-hydroxytryptamine. In an additional open study, including 10 patients with peripheral arterial obstructive disease, a chronic treatment with ketanserin 40 mg t.i.d. for a period of 3 months significantly suppressed the primary platelet aggregation to 5-HT at 2 X 10(-5) M and at 2 X 10(-6) M and significantly lowered the plasma beta thromboglobulin levels. Since 5-HT is a potent mediator of vasospasm, treatment with ketanserin might be of therapeutic value in atherosclerotic diseases, where platelet activation is thought to be involved. PMID- 2931965 TI - Bone scintigraphy and radiography in young athletes with low back pain. AB - Radiographs and bone scans of 40 young athletes with low back pain were reviewed retrospectively to correlate the imaging findings and assess the value of scintigraphy in the diagnosis of these patients. The radiographs were positive for spondylolysis with or without spondylolisthesis in 15 (38%), and scintigraphy showed focal disease in the posterior vertebral elements in 14 (35%). Five patients had positive radiographic studies but normal scans, indicating old injuries; four patients had positive scintigrams but normal radiographs, suggesting early or active injuries. The authors use radiography as the initial examination in the evaluation of patients with low back pain. Scintigraphy is most useful in early stages, when radiographs may be normal; and in cases in which the age and activity of a radiologic abnormality cannot otherwise be accurately determined before therapy. PMID- 2931966 TI - Detection of acute synthetic vascular graft infection with 111In-labeled leukocyte scanning: an animal study. AB - Synthetic vascular graft infection is characterized by late diagnosis due to indolent and nonspecific symptoms. Indium-111-labeled leukocyte imaging holds promise as a diagnostic tool to identify vascular graft infection, but reported data on its accuracy are somewhat sparse and conflicting. In this study, 13 mongrel dogs received Dacron aortic interposition grafts. Seven grafts were contaminated at the time of surgery by topical ATCC Staphylococcus aureus concentrated at 10(8) organisms/ml. Six control animals received no graft contamination. All infected animals were sacrificed on the second postoperative day after 111In leukocyte scanning. The results showed a sensitivity of 71%, specificity of 100%, and accuracy of 85% for the 111In leukocyte study in detecting early graft infections; false-positive leukocyte scans in the early postoperative period were not a problem as has been reported by others. These data indicate that leukocyte scanning for graft infection detection is likely to be clinically valuable. PMID- 2931967 TI - Scanning equalization radiography of the chest: assessment of image quality. AB - An evaluation of the image quality of scanning equalization radiography (SER) of the chest was conducted with 60 volunteer patients. Posteroanterior chest radiographs by SER and conventional methods were compared by six radiologists to determine the adequacy and uniformity of the film exposure and the visualization of normal anatomic structures. The radiographs by the SER technique were deemed to be superior for visualization of most anatomic features. With SER there were no film artifacts from the scanning technique and there was only occasional blurring of some structures with a 4.7-sec scan time. PMID- 2931968 TI - Distal coronary artery perfusion during percutaneous transluminal coronary angioplasty. AB - Perfusion of the coronary artery distal to an occluding angioplasty balloon was performed in 34 patients undergoing coronary angioplasty (PTCA). A randomized crossover study was employed using two exogenous substances as perfusates: lactated Ringer's solution (LR) and a fluorocarbon emulsion (FL), Fluosol-DA 20%. Both substances are electrolyte solutions, but the FL will dissolve more oxygen than the LR. During two attempted coronary artery occlusions of 90 seconds each, we perfused through the central lumen (guidewire channel) of the PTCA catheter at 60 ml/min. With FL perfusion the mean time to onset of angina after occlusion was delayed (41 +/- 21 vs 33 +/- 16 seconds, mean +/- SD; p less than 0.05), the mean duration of angina was shortened (77 +/- 58 vs 92 +/- 70 seconds, p less than 0.05), and the rise in the ST segment of the ECG was reduced (0.15 +/- 0.24 vs 0.2 +/- 0.23 mV, p less than 0.001) when compared to LR perfusion. Balloon occlusion time was able to be extended with FL perfusion (71 +/- 22 vs 59 +/- 22 seconds p less than 0.001). These results indicate that perfusion of the distal coronary artery is possible during PTCA and can reduce ischemia during a prolonged balloon occlusion time. PMID- 2931969 TI - Right ventricular coronary flow in arterial hypertension. AB - Right ventricular (RV) coronary circulation in systemic hypertension offers an opportunity to assess the effects of marked increases in coronary perfusion pressure in vivo without appreciable increases in workload or marked hypertrophy of the cardiac chamber. This study investigates RV coronary circulation in renal hypertensive rats (RHR). Mean arterial pressure rose by 50% to 60% in RHR as compared to control groups and RV mass increased by 15% (7.15 vs 6.19 mg/gm body weight, p less than 0.01). Coronary blood flow, which was measured by left atrial injection of microspheres in conscious rats, was not significantly different between study groups both at rest and after maximal coronary vasodilation with carbochrome (6 mg/kg). However, minimal RV coronary resistance level per gram were significantly elevated (p less than 0.05) in RHR. A second study was designed to further dissociate the effects of arterial hypertension from the effects of changes in RV mass in RHR. In one group, blood pressure was acutely reduced by 1 week of captopril therapy, while RV mass remained high. In the second group, captopril was discontinued after 14 weeks of treatment, allowing arterial pressure to rise, while RV mass, which had regressed with treatment, remained normal. After treatment, RV minimal coronary resistance levels remained high in the short-term-treated hypertensive rats, but returned to normal levels in the long-term-treated RHR. These results suggest the following possibilities: the RV is not immune to the effects of systemic hypertension, coronary structural changes are probably the main factor that accounts for the increase in RV coronary resistance levels, and coronary alterations are amenable to long-term antihypertensive therapy. PMID- 2931970 TI - The eight dental specialties: their origin and rise. PMID- 2931971 TI - Riley Hospital Dental Clinic: dedicated to the child patient. PMID- 2931972 TI - Effects of hematoporphyrin derivative and photodynamic therapy on atherosclerotic rabbits. AB - This study was performed to demonstrate selective uptake of hematoporphyrin derivative (HPD) within actively developing atheroma, to localize the site of uptake of HPD within the atheroma, and to determine the potential for photodynamic therapy (PDT) of atherosclerosis in the rabbit model. Fifteen rabbits were rendered atherosclerotic. Five rabbits received neither HPD nor PDT and 2 rabbits received HPD, 10 mg/kg intravenously, without subsequent irradiation. Eight other rabbits received 5 to 20 mg of HPD intravenously and subsequent intravascular 636-nm laser radiation to either the thoracic aorta or the aortic arch. A total of 32 to 288 J of laser energy was delivered through a 300-mu quartz fiber. All rabbits that received in vivo HPD had red fluorescence of their aortas when placed under ultraviolet light. The pattern of fluorescence corresponded precisely to the pattern of atheroma. In segments that received PDT, light microscopic examination revealed an accumulation of smooth muscle cells at the intimal surface. Fluorescence microscopy revealed a diminishing concentration gradient of HPD from intimal surface layers towards the media. Assessment of treated thoracic aortic segments revealed quantitative and qualitative differences compared with control segments. In the arch-treated segments, however, no changes were seen. It is concluded that HPD localizes within rabbit atheroma, can be detected by fluorescence and is deposited in a diminishing concentration gradient from lumen toward media. Irradiation with 636-nm light may induce qualitative and quantitative changes in atheroma. PMID- 2931973 TI - Lack of effects of copper gluconate supplementation. AB - A double-blind study was done giving 10 mg of copper/day as copper gluconate or placebo capsules for 12 wk. The seven subjects receiving copper gluconate had no change in the level of copper in the serum, urine, or hair. There was also no change in the levels of zinc or magnesium. There was also no significant change in levels of hematocrit, triglyceride, SGOT, GGT, LDH, cholesterol, or alkaline phosphatase. The side effects of nausea, diarrhea, and heartburn were the same in the subjects receiving copper gluconate and subjects receiving placebo capsules. PMID- 2931974 TI - The relationship of various indices of heart size on chest x-ray to the 10-year incidence of hypertension. The Normative Aging Study. AB - A total of 598 males (aged 30-74 years) who had baseline (1961-1970) chest radiography and baseline blood pressure less than 140/90 mmHg were observed prospectively for 10 years. Subjects were participants of the Normative Aging Study, a longitudinal study on aging initiated in 1961 at the Veterans Administration Outpatient Clinic in Boston, Massachusetts. Blood pressures were taken at five- and 10-year follow-up examinations. Multiple logistic regression analysis indicated that the long diameter of the heart (on posteroanterior film) and the cardiac depth (on lateral film) were statistically significant predictors of subsequent hypertension after controlling for baseline body mass index, systolic pressure, and diastolic pressure. A similar model considering various composite indices of heart size indicated that the heart volume was a statistically significant and independent predictor of hypertension. Thus, increases in heart size may precede and predict the development of sustained hypertension. PMID- 2931975 TI - Frequency of hexosaminidase A variant alleles among Ashkenazi Jews and prenatal diagnosis of GM2 gangliosidosis. PMID- 2931976 TI - Accurate and superaccurate gene mapping. AB - Highly accurate gene mapping techniques need to be developed to clone disease genes with unknown defective products. The classical pedigree method and methods based on cytologically observable chromosome aberrations share definite limits in resolution. We quantify the limits in resolution for the pedigree method. We also discuss a technique for gene localization that exploits the possible presence of minute depletions overlapping the disease locus. One can search for such submicroscopic deletions by aiming random probes at them. We show quantitatively that relatively few probes may suffice to hit a target deletion. Choosing which probes to aim should be guided by pedigree studies and by close examination of relevant cytologically observable translocations and deletions. PMID- 2931977 TI - Fragile (X) expression induced by FUdR is transient and inversely related to levels of thymidylate synthase activity. AB - Thymidylate synthase (TS) activity was monitored in fluorodeoxyuridine (FUdR) treated lymphoblasts from individuals carrying the fragile (X) [fra(X)] chromosome. Fra(X) expression and levels of TS activity were measured over a 72 hr period at different cell densities. TS activity was 80%-90% inhibited immediately after exposure to FUdR and remained suppressed for the first 24 hrs. Fra(X) expression was not found until 6-8 hrs after FUdR treatment, and at 24 hrs, reached a maximum expression of approximately 50%. At 48 and 72 hrs, however, increasing levels of TS activity paralleled a dramatic drop in fra(X) expression. High fra(X) expression at 48 and 72 hrs could be maintained by rechallenging cultures with increasing doses of FUdR. At low cell densities, fra(X) expression was maintained at high levels for a much longer period of time. In two lymphoblastoid cell lines from obligate carriers, which either expressed at very low levels or did not express the fra(X) in routine cultures, TS activity was also 90% inhibited but with no corresponding fra(X) expression 12 or 24 hrs after FUdR treatment. We conclude that: FUdR inhibits TS activity immediately and induces fra(X) expression 6-8 hrs later, FUdR-induced fra(X) expression and TS activity are inversely related, the FUdR effect on fra(X) expression and TS activity is time and cell-density dependent, and inhibition of TS activity is a necessary but not sufficient condition for fra(X) expression. PMID- 2931978 TI - Use of nifedipine as monotherapy in the management of hypertension. AB - Calcium antagonists are vasodilators and, therefore, they decrease the peripheral vascular resistance. Acute vasodilation invokes a reflex increase in sympathetic activity that results in positive chronotropic and inotropic effects. These acute effects have been demonstrated both in patients with hypertension and subjects with normal blood pressure values. A theoretic objection to the use of nifedipine as monotherapy in patients with chronic hypertension was that calcium channel blockers would invoke a chronic sympathetic response and, in particular, chronic tachycardia. In this study, the effects of calcium antagonists on ambulatory blood pressure were investigated in patients with essential hypertension who had no evidence of target organ damage. Direct arterial blood pressure measurements, monitored continuously over 24 hours, showed that nifedipine significantly reduced systolic and diastolic blood pressures throughout the day and at night. The variability in blood pressure values was not altered by nifedipine therapy, nor were there significant changes in heart rate. Estimations of left ventricular mass also demonstrated that successful control of blood pressure with nifedipine monotherapy resulted in a significant reduction in the left ventricular mass similar to that achieved with beta blockers and diuretics. Thus, nifedipine may be used effectively as monotherapy in patients with essential hypertension, controlling blood pressure throughout the day and at night. Calcium antagonists are, therefore, useful drugs in the management of hypertension and, in light of the findings reported herein, should be seriously considered as initial therapy. PMID- 2931980 TI - Risk of Down syndrome among relatives of Down syndrome individuals. PMID- 2931979 TI - Clinicopathological conference: an adolescent girl with severe mental impairment and mucopolysacchariduria. PMID- 2931981 TI - A de novo translocation, 14q21q, with a microchromosome-14p21p. AB - A familial translocation, t(14;21)(14p21p;14q21q), in a mother and her child is described. The translocation was ascertained through the birth of a Down syndrome baby with the chromosome constitution 47,XX,-14, +der 14, +der 21,t(14;21)(q11;p12) mat. A 1:3 segregation in the maternal meiosis is suggested for the evolution of the unbalanced chromosome state. The main translocated chromosome 14q21q mimics the product of a Robertsonian translocation, while the 14p21p chromosome has the morphology of a satellited microchromosome. The cytogenetic nature of this translocation is discussed. PMID- 2931983 TI - Recurrence risk in de novo 21q21q translocation Down syndrome. PMID- 2931982 TI - Apical hypertrophic cardiomyopathy in a father and daughter. AB - Apical hypertrophic cardiomyopathy is described in a father and his daughter. In both, identical segments of the left ventricle were involved by the hypertrophic process with differing degrees of severity. We suggest that the morphologic findings described are due to a single gene with an autosomal dominant mode of inheritance. PMID- 2931984 TI - Medical needs of severely developmentally disabled persons residing in the community. AB - Data on the health needs and utilization of medical services were collected on 27 severely developmentally disabled persons residing in the community in order to make recommendations regarding the development of a network of generic services to meet those needs. A surprisingly low incidence of acute illness and emergencies was found, contradicting previous authors' assertions that such a population has excessive medical needs and therefore cannot be served in the community. On the contrary, community placement proved to be advantageous to this group, as they gained access to specialty medical services that were previously unavailable to them as residents of a large public facility. PMID- 2931985 TI - Early vocabulary acquisition by children with Down syndrome. AB - Early acquisition of object names by 6 children with Down syndrome relative to the acquisition pattern of 6 nonretarded children was investigated. Each child was followed for 14 to 21 months. At the start of the study the children with Down syndrome were 17 to 19 months old. The nonretarded children were 9 months old. Results indicated that the children with Down syndrome were at the same level of cognitive development as the nonretarded children at the onset of both comprehension and production of object names. Soon after language acquisition began, however, the language development of the Down syndrome group began to lag behind their cognitive development: Level of vocabulary development was lower than would have been expected based on level of cognitive development. PMID- 2931986 TI - Renal involvement in mixed connective tissue disease. Report of 5 cases. AB - 5 cases with the compatible serological criteria of mixed connective tissue disease described earlier are presented. In 1 of them with a moderate degree of proteinuria, the renal biopsy disclosed membranous nephritis. However, despite the absence of overt clinical renal disease in the other 4 cases, biopsies disclosed membranous nephritis in 1 and mild mesangial proliferative glomerulonephritis in the remaining 3 cases. In the follow-up of these 4 cases, 2 subsequently developed abnormal urinalysis. Electron microscopic examinations demonstrated electron-dense deposits in glomeruli, and 4 of these patients also had microtubular structures in the endothelial cytoplasm. Contrarily to the original concept, our findings suggest that mixed connective tissue disease also induces immune complex disease. PMID- 2931987 TI - Hospitalizations among black women using contraceptives. AB - We analyzed hospitalizations among 26,507 young black women who attended a large metropolitan family planning clinic between 1968 and 1976. Age-adjusted hospitalization rates were compared for women using oral contraceptives, intrauterine contraceptive devices, and depot medroxyprogesterone acetate. Overall, intrauterine contraceptive device and depot medroxyprogesterone acetate users were hospitalized at about the same rate, while women using oral contraceptives were hospitalized 30% less often. The oral contraceptive users were not hospitalized at a higher rate for circulatory disease. Compared to women using intrauterine contraceptive devices, users of oral contraceptives and depot medroxyprogesterone acetate were less likely to be hospitalized for benign breast disease (rate ratios = 0.5 and 0.2, respectively, with 95% confidence limits of 0.3 to 0.7 and 0.1 to 0.5) and for pelvic inflammatory disease. Women were four times as likely to be using depot medroxyprogesterone acetate when they were hospitalized with carcinoma in situ of the cervix, but depot medroxyprogesterone acetate users with at least 3 years of use were less likely to be hospitalized for carcinoma in situ than comparable groups of oral contraceptive and intrauterine contraceptive device users. PMID- 2931988 TI - A randomized crossover comparison of two low-dose contraceptives: effects on serum lipids and lipoproteins. AB - The effect of a triphasic combination of ethinyl estradiol and levonorgestrel upon various lipoprotein parameters was compared to that of a preparation that contained ethinyl estradiol and desogestrel on days 6, 11, 21, and 28 of a control cycle, the third cycle of treatment with either ethinyl estradiol/levonorgestrel or ethinyl estradiol/desogestrel (11 volunteers each), the third cycle of a 3-month washout period, and the third treatment cycle after crossover change of the preparations. Significant increases were found in total triglycerides (15% to 20%) and phospholipids (8%) with both preparations, whereas total cholesterol and lipoprotein Lp(a) were not altered. High-density lipoprotein triglycerides (50% to 60%) and high-density lipoprotein-3 cholesterol (10% to 15%) were elevated by both contraceptives, high-density lipoprotein cholesterol and alpha-lipoprotein cholesterol only by ethinyl estradiol/desogestrel (11%), whereas high-density lipoprotein phospholipids, high density lipoprotein-2 phospholipids, high-density lipoprotein-3 phospholipids, and high-density lipoprotein-2 cholesterol were not influenced. Both ethinyl estradiol/levonorgestrel and ethinyl estradiol/desogestrel increased apolipoproteins A (14%), A-I (20% to 30%), and A-II (25% to 35%) significantly. Very low-density lipoprotein triglycerides were elevated (30%) only by ethinyl estradiol/desogestrel, and low-density lipoprotein phospholipids (20%) by both ethinyl estradiol/levonorgestrel and ethinyl estradiol/desogestrel, whereas the other parameters, very low-density lipoprotein phospholipids, very low-density lipoprotein cholesterol, pre-beta-lipoprotein cholesterol, low-density lipoprotein triglycerides, low-density lipoprotein cholesterol, beta-lipoprotein cholesterol, and apolipoprotein B, were not significantly changed. Provided that the assumption is correct that high low-density lipoprotein cholesterol and apolipoprotein B and low high-density lipoprotein subfractions and apolipoprotein A are associated with an elevated risk of atherosclerosis, the results seem to represent beneficial rather than deleterious side effects of the low-dose oral contraceptives. PMID- 2931989 TI - Adverse ocular reactions possibly associated with isotretinoin. AB - A total of 261 adverse ocular reactions occurred in 237 patients who received isotretinoin, a commonly used drug in the treatment of severe cystic acne. Blepharoconjunctivitis, subjective complaints of dry eyes, blurred vision, contact lens intolerance, and photodermatitis are reversible side effects. More serious ocular adverse reactions include papilledema, pseudotumor cerebri, and white or gray subepithelial corneal opacities; all of these are reversible if the drug is discontinued. Reported cases of decreased dark adaptation are under investigation. Isotretinoin is contraindicated in pregnancy because of the many reported congenital abnormalities after maternal use (including microphthalmos, orbital hypertelorism, and optic nerve hypoplasia). PMID- 2931990 TI - Time use of mothers with preschool children: a pilot study. AB - This pilot study describes and compares the time use for physical child care of two groups of mothers--those with physically handicapped preschoolers (N = 16) and those with normal preschoolers (N = 21). Each mother completed a questionnaire on the time she spent in three categories of physical child care activities. These activities included feeding, personal care, and transportation for physical care. Investigators collected data on both frequency and duration. They reported descriptive data for all categories separately and combined. The results of the study show that the mothers of the physically handicapped preschoolers spent significantly more time engaged in physical child care activities than did the mothers of normal preschoolers. Results also show a high correlation between frequency and duration data for physical child care. The results strongly suggest that the mothers of physically handicapped preschoolers spend significantly more time in physical child care than do the mothers of normal preschoolers. They also suggest that frequency data alone could be collected in further studies in this area without appreciably reducing the accuracy of the results. PMID- 2931991 TI - Brief or new: the thigh feeder. PMID- 2931992 TI - Tissue reaction to primers used in the "single-step" bonding system. AB - A large number of direct-bonding systems have been introduced for use by orthodontists. Although these agents are used for direct bonding of brackets to enamel, contact with skin, oral mucosa, and gingiva is not uncommon. While these products have wide clinical use, their biocompatibility has not been extensively investigated. The present study was undertaken to determine the effects of the primer component of Mono-Lok and the primer component of Control on gingiva. Three adult and one juvenile Macaca mulatta monkeys were used in this investigation. In two adults and the one juvenile animal, the primer component of Mono-Lok was applied to the right buccal surfaces of teeth; in the remaining adult animal, the primer component of Control was applied to the right buccal surfaces of teeth. The excess material was extended 5.0 mm onto the gingival tissues and for 3 minutes the cheeks and saliva were kept away from the sites to be tested. Saline solution was applied to the left buccal segments in all animals. Primer and saline solution were applied at 3-day intervals for a period of 21 days. The gingival tissues were examined clinically and biopsied for histologic evaluation. The gingiva in contact with the primer component of Mono Lok exhibited pronounced inflammatory changes and was characterized by redness, swelling, and spontaneous bleeding. Histologic observations confirmed these findings by showing a marked inflammatory cellular response characterized by eosinophils. In contrast to these findings, the gingiva that was in contact with the primer component of Control or saline solution exhibited normal gingival architecture.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2931994 TI - Influence of training on skeletal muscle enzymatic adaptations in normal and diabetic rats. AB - Muscle homogenates representing slow-twitch oxidative, fast-twitch oxidative glycolytic, fast-twitch glycolytic, and mixed fiber types were prepared from normal, diabetic, and insulin-treated diabetic rats. Diabetes was induced by injection of 80 mg . kg-1 of streptozotocin. The activities of citrate synthase, succinate dehydrogenase, and 3-hydroxyacyl-CoA dehydrogenase were employed as markers of oxidative potential, whereas phosphorylase, hexokinase, and phosphofructokinase activities were used as an indication of glycolytic capacity. Diabetes was associated with a general decrement in the activity of oxidative marker enzymes for all fiber types except the fast-twitch glycolytic fiber. In contrast, the fast-twitch glycolytic fibers demonstrated the greatest decline in glycolytic enzymatic activity. Insulin-treated animals, either trained or untrained, exhibited enzyme activities similar to their normal counterparts. Exercise training of diabetic rats mimicked the effect of insulin treatment and caused a near normalization of the activity of the marker enzymes. These findings suggest that the enzymatic potential of all skeletal muscle fiber types of diabetic rats may be normalized by exercise training even in the absence of significant amounts of insulin. PMID- 2931993 TI - Laminin inhibits the recognition of tumor target cells by murine natural killer (NK) and natural cytotoxic (NC) lymphocytes. AB - Tumor cells sensitive to lysis by murine natural killer (NK) or natural cytotoxic (NC) cells were shown to bind laminin. They bound 125I-labeled laminin in a time- and concentration-dependent manner, and binding of the radioactive laminin was inhibited by excess cold laminin. In the presence of laminin, cell-cell aggregation occurred. Murine tumor cells not sensitive to NK/NC-mediated killing bound much less laminin, and laminin did not induce aggregation of these cells. The addition of exogenous laminin to NK or NC cytotoxicity assays reduced target lysis in a dose-related manner. Reduction of lysis was due to an inability of NK/NC cells to bind to the targets. Target cells pretreated with laminin were reduced in their ability to cold-target compete for NK-mediated lysis of untreated target cells. These effects were unique to laminin. The control proteins (fibronectin and thyroglobulin) had no effect on NK activity. Finally, inhibition of cytolytic activity by laminin appeared to be specific for NK/NC cells. Laminin had no effect on cytolysis mediated by alloimmune cytotoxic T lymphocytes regardless of whether the targets did or did not bind laminin. PMID- 2931995 TI - Altered aortic and cremaster muscle prostaglandin synthesis in diabetic rats. AB - Alterations in the synthesis and release of prostaglandins have been reported in humans and animal models of diabetes mellitus. In the present study synthesis and release of prostaglandins by thoracic aorta and cremaster muscle of rats with streptozotocin-induced diabetes of 8 wk duration was compared with age-matched controls. Prostaglandin synthesis was assessed by the measurement of immunoreactive prostaglandin E2 (PGE2) and 6-ketoprostaglandin F1 alpha (6-keto PGF1 alpha) release and by quantifying metabolism of exogenous [1-14C]arachidonic acid by thoracic aortic rings and minced cremaster muscle. The cremaster muscles from diabetic rats released significantly greater quantities of PGE2 and 6-keto PGF1 alpha and PGE2. In contrast, the aortas from diabetic rats released smaller quantities of 6-keto-PGF1 alpha and PGE2 and exhibited reduced 6-[1-14C]keto-PGF1 alpha. These studies indicate that diminished prostacyclin (PGI2) and/or PGE2 production is not a general feature of all diabetic vascular tissues, suggesting that large and small blood vessels may not be similarly affected by diabetes in regard to the metabolism of exogenous arachidonic acid and the synthesis and release of prostaglandins. Furthermore, the vascular changes often observed in conjunction with diabetes, i.e., alterations in vascular reactivity and microangiopathy in small blood vessels and atherosclerosis of large blood vessels may be related in some way to the segmental differences observed in prostaglandin synthesis. PMID- 2931996 TI - Gastric mucosal blood flow measured by laser-Doppler velocimetry. AB - To determine the feasibility of measuring gastric mucosal blood flow by laser Doppler velocimetry (LDV), we utilized two LDV flowmeters to monitor blood flow in mucosa and serosa of chambered canine stomach. In isolated, nonautoregulating gastric segments vasodilated with isoproterenol, LDV mucosal and muscularis blood flows were both linearly related to total electromagnetic blood flow during step increases in perfusion pressure. To assess the depth of the LDV measurement, we recorded reactive hyperemia following arterial occlusion. Reactive hyperemia was frequently registered in the mucosa but rarely in muscularis. Placing a layer of nonperfused mucosa-submucosa between the probe and the perfused mucosa abolished the resting LDV mucosal flow signal and attenuated the recording of peak hyperemia by 85%. Furthermore, intra-arterial infusions of both adenosine and isoproterenol frequently increased LDV mucosal flow and decreased LDV muscularis flow, although total flow was consistently increased. These findings indicate that our LDV instruments yield linear, superficial measurements of gastric blood flow in either mucosa or muscularis. Although calibration in absolute units remains to be achieved, our results demonstrate that LDV is a practical means of studying the gastric mucosal microcirculation. PMID- 2931998 TI - Contraction regulates myosin synthesis and myosin content of cultured heart cells. AB - Cultured neonatal rat heart cells are a useful model for studying the regulation of myocyte growth. The myosin content of heart cells increases between days 1 and 4 in culture. To determine if contraction per se can regulate myocyte growth, myosin content and protein synthesis were compared in spontaneously contracting and noncontracting cultured heart cells. Myosin content, assayed as the total myosin ATPase activity per culture dish, was significantly increased in contracting cells after 3, 4, and 5 days in culture. Protein synthesis was measured by incorporation of [14C]lysine into total cell protein and into sodium dodecyl sulfate-polyacrylamide gel electrophoresis resolved myosin. Contraction stimulated both total cell protein content and protein synthesis by day 3 in culture. Compared with heart cells arrested with 50 mM KCl, myosin synthesis was significantly increased by 96, 112, and 46% at days 2, 3, and 4, respectively. Similar results were observed when myosin content and protein synthesis in contracting myocytes were compared with cells arrested with either 25 mM KCl or 10(-5) M verapamil. The present studies suggest that contraction increases the myosin content in cultured heart cells and that this increase is mediated via a stimulation of myosin synthesis in association with cell growth. PMID- 2931997 TI - Effects of synthetic atrial natriuretic factor in the isolated perfused rat kidney. AB - It is known that atrial extracts (AE) and synthetic atrial natriuretic factor (ANF) can increase glomerular filtration rate (GFR) and electrolyte and water excretion both in vivo and in vitro. It is not clear, however, if ANF-induced increases in filtered load (increased GFR) are required to produce natriuresis and diuresis. We perfused isolated rat kidneys with AE or synthetic ANF at constant pressure in a single-pass system. Extracts of atrial tissue (1 mg/ml) and high concentrations of ANF (31 and 61 ng/ml) significantly increased both GFR and electrolyte and water excretion. During continued infusion of ANF, GFR stabilized at increased levels, but sodium and water excretion continued to increase. After the termination of infusions, GFR and potassium excretion returned to control levels, but sodium and water excretion remained significantly elevated. Infusion of a low concentration of ANF (3 ng/ml) significantly increased sodium and water excretion without changing either GFR or potassium excretion. We conclude that increases in GFR are not a prerequisite for natriuresis and diuresis in response to ANF, but that increases in GFR can potentiate the response. Furthermore, our data suggest that ANF increases potassium excretion only if it increases GFR. PMID- 2931999 TI - Decreased auxotonic sarcomere shortening in hypertrophied rabbit myocardium. AB - Auxotonic sarcomere length change occurs during isometric twitches of isolated cardiac muscle preparations. To assess the amount of internal work in hypertrophied myocardium, we measured auxotonic sarcomere length change during isometric tension development over a range of initial muscle and sarcomere lengths. Hypertrophy was produced by banding the pulmonary artery, which resulted in an increase in the ratio of right ventricular free wall weight to total ventricular weight (normal 0.19 +/- 0.004; hypertrophy 0.35 +/- 0.008; P less than 0.001). Right ventricular free wall trabeculae and papillary muscles were studied with optical and mechanical instrumentation, including a helium-neon laser, to measure sarcomere length and isometric twitch parameters. The resting sarcomere length-resting tension relationship was shifted to the left of normal in the hypertrophied preparations (P less than 0.001). The relationship of sarcomere length at the peak of the twitch with total tension at the same instant was shifted downward and to the right of normal in hypertrophy (P less than 0.01). For the same amount of total tension development there was less than normal sarcomere shortening in the hypertrophied preparations (P less than 0.001). Consequently, there is less than normal work per sarcomere during auxotonic sarcomere shortening in hypertrophied heart muscle. Less sarcomere work for a particular functional state is important to consider in the assessment of the basis of myocardial function in compensated pressure overload hypertrophy. PMID- 2932000 TI - Measurement of erythrocyte velocity by use of a periodic differential detector. AB - An optical velocimeter employing a linear array of photodiodes has been developed and utilized for measuring erythrocyte velocities in the microcirculation. A magnified image of a microvessel is projected and aligned on a one-dimensional array of photodiodes. Photocurrent from odd-ordered diodes is summed, photocurrent from even-ordered diodes is summed, and a signal proportional to the difference between these two currents is produced by a differential amplifier. The center frequency of the output signal of the differential amplifier is proportional to the erythrocyte velocity. After lowpass filtering the output of the differential amplifier, a signal proportional to its frequency and therefore velocity is produced by a frequency-voltage converter. In vitro calibration with a moving dried smear of erythrocytes illustrated a linear relation between the output of the frequency-voltage converter and erythrocyte velocity for a wide range of velocities and magnifications. The system produces a stable zero output at zero velocity and had an estimated frequency response of greater than 40 Hz in vivo. Volumetric flow rates computed from velocity and diameter measurements at arteriolar bifurcations in the rat cremaster muscle were consistent with mass conservation. PMID- 2932001 TI - Pathophysiologic characteristics of venous thrombosis. AB - Experimental and clinical studies are reviewed briefly to assess the role of the vessel wall, stasis, clotting factors and their inhibitors, and the fibrinolytic system in the pathogenesis of venous thrombosis. PMID- 2932002 TI - Diagnostic methods for deep vein thrombosis: venous Doppler examination, phleborheography, iodine-125 fibrinogen uptake, and phlebography. AB - Since clinical diagnosis of DVT is often inaccurate, it has become accepted that an objective means of diagnosing clot in the deep venous system becomes critically important in the management of these patients. Important to understanding the diagnostic capabilities of any test are the anatomic and physiologic characteristics of the deep venous system. The venous Doppler examination monitors the velocity of blood flowing through a particular vein. Doppler probes in the 5 to 10 mHz range are routinely used. Respiratory variation is a normal finding due to a diminished flow signal during inspiration, followed by a progressive increase in flow signal during expiration. Characteristics of the spontaneous flow signals are the most important part of interpreting the venous Doppler examination. In addition, the response to distal or proximal compression (augmentation) adds important information to the interpretation; however, the response during any augmentation maneuver depends on the rapidity of compression, the force of compression, the quantity of blood in the veins at the time of compression, and the distance between the Doppler probe and the compression point. The literature reports a wide range of sensitivity and specificity for the Doppler examination, but there is uniform agreement and an observable trend that physicians with a large experience and a dedicated interest will obtain much better results than physicians with less experience and less interest. Phleborheography is a six-channel volumetric plethysmographic technique that monitors volume changes in the lower extremities associated with respiration and foot and calf compression. The volumetric tracings obtained are similar to the velocity profiles obtained on the venous Doppler examination. The criteria used in interpreting phleborheographic tracings are respiratory waves and baseline elevation (major criteria), and prominent arterial pulse waves and foot emptying (minor criteria). Previously reported overall sensitivities for detecting DVT are 83 to 93 percent, with sensitivities of detecting proximal vein thrombosis of 92 to 96 percent. Specificities have been reported to be 87 to 97 percent. In a prospective analysis of 126 extremities with phleborheography and phlebography carried out within the same 24 hour period at Temple University Hospital, we found an overall sensitivity of 79 percent (51 of 65 patients); however, the sensitivity for proximal vein thrombosis was 91 percent (49 of 54 patients).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2932003 TI - [Tissue oxygen tension in fetuses with chronic hypoxia during birth]. PMID- 2932004 TI - [Rheologic and hemostatic indices of the blood in newborn infants experiencing acute hypoxia during birth]. PMID- 2932005 TI - [Fetal echocardiography in the 2d pregnancy trimester]. PMID- 2932006 TI - [Effect of late pregnancy toxicosis on the adaptability of the fetus and the newborn]. PMID- 2932007 TI - [Effect of acureflexotherapy on the state of the fetus in late pregnancy toxicoses]. PMID- 2932008 TI - [State of the fetoplacental system in the presence of a post-cesarean section uterine cicatrix]. PMID- 2932009 TI - [Effect of sigetin and glucose injections during pregnancy on the resistance to anoxia of premature normal growth and growth retarded fetuses (experimental study)]. PMID- 2932010 TI - [Course of pregnancy and labor and pregnancy outcome for mother and fetus in women infected with Mycoplasma hominis]. PMID- 2932011 TI - [Oxygen regime in healthy newborn infants during adaptation to extrauterine life]. PMID- 2932012 TI - [Age-related dynamics of natural killer activity and basic lymphocyte populations in the peripheral blood of healthy women]. PMID- 2932013 TI - [Laser puncture in the combination therapy of pregnancy nephropathy combined with hypertension]. PMID- 2932014 TI - [Significance of the functional activity of lymphocytes in the pathogenesis of pregnancy nephropathy]. PMID- 2932015 TI - [Proliferative activity of T-lymphocytes in pregnant women with diabetes mellitus]. PMID- 2932016 TI - [Role of chlamydial infections in obstetric pathology]. PMID- 2932017 TI - [Potentialities of ultrasonic diagnosis in pregnant women with diabetes mellitus]. PMID- 2932018 TI - [The problem of low birth weight infants]. PMID- 2932019 TI - [Echoscopic data on the effect of methylergometrin on the course of the placental and early postpartum stages]. PMID- 2932020 TI - [Immunochemical study of the urinary proteinogram in pregnancy nephropathy]. PMID- 2932021 TI - [Use of heparin in the combination therapy of parturients having undergone premature detachment of a normally positioned placenta]. PMID- 2932022 TI - [Effectiveness of reflex stimulation of labor]. PMID- 2932023 TI - [Formation of pituitary-gonadal relations in girls with accelerated physical development]. PMID- 2932024 TI - [Possibilities of using echography to detect pathological processes in the endometrium]. PMID- 2932025 TI - [Current methods of diagnosing endometrial polyps]. PMID- 2932026 TI - [Use of the CO2-laser for treating benign cervix diseases]. PMID- 2932027 TI - [Effectiveness of sinusoidally-modulated currents and currents of supersonic frequency in the treatment of patients with chronic recurring salpingo oophoritis]. PMID- 2932029 TI - [Prevention of complications after surgery for uterine cancer]. PMID- 2932028 TI - [State of the urinary tract in patients with genital endometriosis before and after treatment]. PMID- 2932031 TI - Follicular mucinosis. A reaction pattern in follicular epithelium. AB - Follicular mucinosis is a histologic term for a reaction pattern in follicular epithelium. Although it is the sine qua non for alopecia mucinosa as a disease sui generis, it may occur in a variety of unrelated conditions, which may be inflammatory, hamartomatous, hyperplastic, or neoplastic. Follicular mucinosis is rare in plaque and nodular lesions of mycosis fungoides, but when it occurs, the malignant lymphoma is not related to the condition known as alopecia mucinosa. In short, alopecia mucinosa is a wholly benign condition and is not premonitory or an early aspect of mycosis fungoides. Follicular mucinosis is not synonymous with alopecia mucinosa but is analogous to other histologic reaction patterns of cutaneous epithelium such as epidermolytic hyperkeratosis, focal acantholytic dyskeratosis, and cornoid lamellation. PMID- 2932030 TI - [Current concepts on the significance of genital herpes infections in obstetric and gynecologic pathology]. PMID- 2932032 TI - Effect of theophylline on the proportion and function of T-suppressor cells in asthmatic children. AB - T-cell subpopulations and their function were studied in asthmatic children with or without theophylline therapy. A decreased proportion and function of theophylline-sensitive T-suppressor cells was found in fresh peripheral blood of asthmatic children. Following peripheral blood mononuclear cells (PBMC) incubation in theophylline-free medium, the proportion of theophylline-sensitive T-cells in asthmatic children treated with theophylline was elevated to normal values. However, their suppressive effect on control lymphocyte proliferation was unchanged. PMID- 2932033 TI - Sedation and cerebral angiography. The effects of pentazocine and midazolam on arterial carbon dioxide tension. AB - A study of the effects of sedation on arterial blood gases in patients undergoing cerebral angiography was performed. Twenty-one patients received pentazocine (30 mg) and midazolam (5-22.5 mg) and arterial carbon dioxide and oxygen tensions were measured from radial artery samples before and during the procedure. A statistically significant rise in arterial carbon dioxide tension was demonstrated. It is suggested that this may cause a rise in intracranial pressure by increasing cerebral blood flow in a group of patients in whom there is a high incidence of raised intracranial pressure. The clinical significance of this increase in arterial carbon dioxide tension is discussed. PMID- 2932034 TI - Respiratory depression following midazolam. PMID- 2932035 TI - [How reliable is a hot-wire anemometer?]. AB - To examine the advantage of hot-wire anemometer for clinical use, we have checked two types of this tools with respect to reliability and validity. It was found that electronic suppression of noise caused a distortion of the measurements. Furthermore changes of transducers were also responsible for deviations from true values. We require of the manufacturer to indicate the threshold of perception and the coefficient of variation for repeated measurements with several transducers. We recommend a simple rule which permits an estimation of the limits of reliable measurements for clinical use depending on the threshold of the equipment and on the parameters of ventilation. PMID- 2932036 TI - A Kunitz type of proteinase inhibitor isolated from boar seminal vesicle fluid. AB - Using immunoaffinity chromatography on a Sepharose 4B column with adsorbed antibodies to the basic inhibitor in bovine organs (Kunitz-type), a proteinase inhibitor was isolated from boar seminal vesicle fluid. The isolated protein inhibited acrosin, trypsin, plasmin and chymotrypsin, but not kallikrein. Its molecular weight determined by gel filtration on Sephadex G-50 was 9,500 (+/- 500) and by SDS electrophoresis in polyacrylamide gel 12,000 (+/- 500) daltons. The protein was demonstrated by immunoprecipitation only in boar seminal vesicle fluid and seminal plasma, and by indirect immunofluorescence on ejaculated spermatozoa and in the epithelium of boar seminal vesicles. This inhibitor is the first acrosin inhibitor specific for the genital organs, which evidently belongs to the group of Kunitz type inhibitors, to be described. PMID- 2932037 TI - Inactivation of atracurium in human and rat plasma. AB - The contribution of enzyme-catalyzed hydrolysis to inactivation of atracurium in human and rat plasma was determined in vitro by inhibiting the enzyme carboxylesterase with triorthotolyl phosphate. The inhibitor was removed by centrifugation and aspiration. Atracurium was then added to both the control and the inhibited plasma samples, and all samples were incubated at 37 degrees C for 45 min. The amount of atracurium present in aliquots of plasma was determined using a bioassay technique in anesthetized rats. Inactivation of atracurium proceeded rapidly in control rat plasma but was markedly slowed in samples treated with the inhibitor of carboxylesterase. In contrast, the inactivation was slow in control human plasma, and inhibition of carboxylesterase produced only marginal, if any, effects. We conclude that the inactivation of atracurium proceeds, in part, by enzyme-catalyzed ester hydrolysis. In species with high enzyme activity in plasma, e.g., the rat, enzyme-catalyzed hydrolysis is clearly evident. In humans, the level of enzyme activity is low and the contribution of enzyme-catalyzed inactivation is less manifest. By exclusion, Hofmann elimination or other reactions probably represent the major inactivation pathway in humans. PMID- 2932038 TI - Intracranial pressure after atracurium in neurosurgical patients. AB - In order to investigate the usefulness of atracurium for neurosurgical anesthesia, we studied its impact on intracranial pressure (subarachnoid bolt) mean arterial pressure (radial artery catheter) and cerebral perfusion pressure (mean arterial pressure-intracranial pressure) in 20 patients undergoing elective craniotomy for brain tumor excision. General anesthesia was induced with thiopental, 4 mg/kg intravenously, and maintained with 70 percent nitrous oxide in oxygen. Ventilation was controlled by face mask, with end-tidal CO2 held constant. Once intracranial pressure and mean arterial pressure had stabilized, the response to atracurium, 0.5 mg/kg intravenously, was continuously recorded for 5 min in 10 patients. An additional 10 patients received no atracurium and served as matched controls. Thiopental caused reductions in ICP in both groups of patients. Comparing the responses of the patients who received atracurium with those who did not, we found that atracurium had no significant effect on intracranial pressure, mean arterial pressure or cerebral perfusion pressure. Based on these data we conclude that atracurium appears to be preferable to the other available neuromuscular blocking agents that have been evaluated for neurosurgical anesthesia. PMID- 2932040 TI - Fine tuning the priming principle. PMID- 2932039 TI - Intramuscular midazolam for pediatric preanesthetic sedation: a double-blind controlled study with morphine. PMID- 2932041 TI - The priming principle and the open eye-full stomach. PMID- 2932042 TI - Patients with Huntington's chorea may respond normally to succinylcholine. PMID- 2932043 TI - The accuracy of "pull-through" pressure measurements and papaverine testing. AB - Intra-arterial pressure measurements have been made in a group of vascular patients using two different methods. The pull-through method, without systemic pressure monitoring, is compared with a technique employing simultaneous radial and femoral arterial puncture. In both techniques, pressures are measured at resting flow and during papaverine induced hyperaemia. PMID- 2932044 TI - Aseptic knee effusion associated with calcified guinea worms. AB - Reported is a case of aseptic knee effusion associated with the presence of a calcified guinea worm, Dracunculus medinensis, in close proximity to the joint. The patient, a native of Nigeria, presented with chronic right knee pain and swelling. He did well with symptomatic treatment including non-steroidal antiinflammatory drugs, rest, ice, and elevation of the leg. Dracunculiasis is prevalent in parts of Asia and Africa, but has been described only rarely in the United States. PMID- 2932045 TI - Successful treatment of pulmonary lymphangiomyomatosis with oophorectomy and progesterone. AB - A 35-yr-old woman, with profound dyspnea at rest and failure to thrive, asked to be evaluated at Stanford Medical Center. She requested a second opinion after entering death counseling in another institution because of an unrelenting, deteriorating course caused by pulmonary lymphangiomyomatosis. Her recurring right chylous pleural effusion was drained by chest tube, a LaVeen shunt was placed to decompress her severe chylous ascites, an oophorectomy was performed, large dose progesterone (medroxyprogesterone acetate) was initiated intramuscularly, and during her hospitalization she was fed by total parenteral nutrition. She was discharged mildly improved after 2 months. Now, 3 yr later, her pulmonary function tests and chest radiographs are improved, and she walks 2 miles per day and teaches school full time. Extensive hormonal analysis did not reveal an endocrinologic abnormality that could explain the pathophysiology of her disease. However, the patient had multiple human chorionic gonadotropin injections before becoming ill, as have a number of other patients who have developed this disease. This report is an example of successful treatment of severe pulmonary lymphangiomyomatosis. PMID- 2932046 TI - Antibody to hepatitis B surface antigen and screening before hepatitis B vaccination. PMID- 2932047 TI - Screening of health care workers before hepatitis B vaccination: more questions than answers. PMID- 2932048 TI - Spectinomycin and cholestatic jaundice. PMID- 2932049 TI - Medical and dental coordination in juvenile rheumatoid arthritis. PMID- 2932050 TI - Abnormalities of the nucleus basalis in Down's syndrome. AB - One of the most striking manifestations of Down's syndrome is profound mental retardation. Furthermore, after 35 years of age, many patients with Down's syndrome develop clinical and pathological features of Alzheimer's disease. Since brains of patients with Alzheimer's disease show significant loss of neurons in the nucleus basalis of Meynert (nbM), we sought to establish normal standards of nbM neurons in persons with Down's syndrome and to determine whether reductions in the number of neurons occur with increasing age. The number and size of neurons in the nbM were measured in selected sagittal sections from 5 patients with Down's syndrome and 5 age-matched controls. The patients (age range, 16 to 56 years) had 29% fewer nbM neurons than controls, and the oldest patient had the lowest cell count of all subjects. The size of nbM neurons did not differ significantly between the two groups. Our results show that the nbM contains fewer neurons in young persons with Down's syndrome than in normal controls and suggest that the number of these nerve cells may be further reduced in older persons with Down's syndrome. PMID- 2932051 TI - Rehabilitation of older people. PMID- 2932052 TI - Measurement in rehabilitation. PMID- 2932053 TI - Independent living: an update for the mid-eighties. PMID- 2932054 TI - Indirect enzyme-linked immunosorbent assay for the mycotoxin zearalenone. AB - A competitive indirect enzyme-linked immunosorbent assay (ELISA) was developed for the detection of zearalenone, an estrogenic mycotoxin. Zearalenone was converted to zearalenone-6'-carboxymethyloxime and conjugated to bovine serum albumin and poly-L-lysine for use as immunogen and solid-phase marker, respectively. Immunization of rabbits with the bovine serum albumin conjugate resulted in zearalenone antibody titers of 20,480 in 11 weeks. A competitive indirect ELISA was conducted by simultaneously incubating zearalenone with zearalenone antiserum over zearalenone-6'-carboxymethyloxime poly-L-lysine solid phase and then determining the bound rabbit immunoglobulin with goat anti-rabbit peroxidase conjugate. Response range for zearalenone in the resulting competition curve was between 1 and 50 ng/ml. Reactivities of this antiserum for alpha zearalenol, beta-zearalenol, alpha-zearalanol, and beta-zearalanol were, respectively, 50, 12, 6, and 3% of that found for zearalenone. By using the competitive indirect ELISA, zearalenone was detectable in methanol-water extracts of corn, wheat, and pig feed samples. PMID- 2932055 TI - Allergenic extracts regulatory progress in the USA. PMID- 2932056 TI - The effect of substrate modification on porcine pancreatic alpha-amylase subsite binding: hydrolysis of substrates containing 2-deoxy-D-glucose and 2-amino-2 deoxy-D-glucose. AB - Modified alpha-D-(1----4)-glucans containing a small proportion of 14C-labeled 2 deoxy-D-glucose or 2-amino-2-deoxy-D-glucose were examined as substrates for porcine pancreatic alpha-amylase (PPA). Cyclomaltoheptaose containing single 2 deoxy-D-glucose residues, synthesized by incubation of 2-deoxyglucosylglycogen with cyclomaltodextrin glucanotransferase in the presence of Triton X-100, was hydrolyzed by PPA to produce 2-deoxy-D-glucose; two isomers of 2-deoxymaltose, and a mixture of modified maltotrioses. These results indicate that 2 deoxymaltose, and a mixture of modified maltotrioses. These results indicate that 2-deoxy-D-glucose may be productively bound at all five subsites of the PPA active site. Reaction kinetics and the distribution of products formed suggest, however, that productive binding of the modified residue does not occur readily at the point of catalytic attack (subsite 3) and that the preferred position of hydrolysis of modified substrates may be different from that of unmodified substrates. Results of PPA hydrolysis of glycogen containing [14C]-2-amino-2 deoxy-D-glucose showed that a modified trisaccharide and a modified disaccharide were the smallest substituted products formed. Analysis of these products indicated that they did not contain modified residues at their reducing ends. Formation of the observed 2-amino-2-deoxy-maltooligosaccharides is consistent with a scheme where productive binding of 2-amino-2-deoxy-D-glucose is allowed at subsites 1, 2, 4, and 5, but not at subsite 3, the subsite at which hydrolysis occurs. PMID- 2932057 TI - [Anticancer treatment with a combination of antimetabolites of polyamine and pyrimidine]. AB - A combined efficacy of the polyamine antimetabolites, alpha difluoromethylornithine (DFMO) and methylglyoxal-bis-guanylhydrazone (MGBG) with two fluorinated pyrimidines was studied. DFMO, MGBG, 5-FU and 5'-deoxy-5 fluorouridine (5'-DFUR) were administered intraperitoneally to BALB/c nu/nu mice bearing xenotransplanted human gastric cancer for 5 consecutive days. Similar antitumor efficacies were observed in 3 groups treated with DFMO plus MGBG, DFMO, MGBG plus 5-FU as well as DFMO, MGBG plus 5'-DFUR. The two groups on 5-FU or 5' DFUR alone did not differ in antitumor effects from the control, although reasonable levels of 5-FU were involved in tumor tissues. Hepatic and splenic 5 FU levels after 5-FU administration were significantly higher than those after 5' DFUR, and marked decrease in mouse body weight was caused by 5-FU alone as well as 5-FU plus polyamine antimetabolites for 5 consecutive days. DNA biosynthesis and spermine levels in the tumor tissues on day 2 after cessation of the treatments dropped in 3 groups with DFMO plus MGBG, DFMO, MGBG plus 5'-DFUR as well as DFMO, MGBG plus 5-FU, while on day 6 there was little difference between the control and treated groups. These data suggest that combination with 5-FU or 5'-DFUR does not enhance the antitumor activity of polyamine antimetabolites by this experimental regimen. PMID- 2932058 TI - [Phase I study of 5'-deoxy-5-fluorouridine (5'-DFUR)]. AB - A phase I study of a new fluorinated pyrimidine compound, 5'-deoxy-5 fluorouridine (5'-DFUR), was performed in 37 patients with various malignant cancers. Starting dose was 600 mg/m2/day (900 mg/body/day) and escalated up to 3900 mg/body/day. The dose given was divided into 3 administrations a day for 5 consecutive days. Subjective symptoms were observed in cases given a dose of over 2,100 mg/body/day. Gastro-intestinal disturbances such as nausea, vomiting and anorexia were the major side effects. In the hematological and urinary examinations, no severe abnormal signs were observed. The maximum tolerated dose was considered to be 2.100 mg/body/day, and the dose-limiting factor was gastro intestinal disturbance. 5-FU levels were determined in the serum and tumor tissues. 5'-DFUR was well absorbed. The 5-FU level in tumor tissue was very high at 2 to 3 hours post-dose and then rapidly decreased, being 0.05 microgram/g 12 hours after administration. The optimal dosage for a phase II study was suggested to be less than 2,100 mg/body/day. PMID- 2932059 TI - [Phase II study of 5'-deoxy-5-fluorouridine (5'-DFUR) in patients with malignant cancer--a multi-institutional cooperative study]. AB - A phase II study of oral 5'-deoxy-5-fluorouridine (5'-DFUR) was conducted on a multi-institutional basis. Six hundred and ninety-two cases were entered into this study and evaluated by the extramural review committee. In 437 evaluable cases the response rate was 16.0%, 13 CR and 57 PR. The response rate of gastric cancer was 14.3%, 1 CR and 19 PR out of 140 evaluable cases, that of colorectal cancer was 9.2%, 1 CR and 6 PR out of 76 evaluable cases, and that of breast cancer was 35.9%, 11 CR and 26 PR out of 103 evaluable cases. The response rate was high with a long-lasting efficacy in breast cancer. Although the number of cases was small, PR was observed in 3 cases of head & neck, and in 1 case each of esophagus, gall-bladder and thyroid cancer. The optimal daily dosage was considered to be 800-1,200 mg/body/day. The tumor began to decrease in size within 8 weeks of treatment in most of the responded cases. Side effects were observed in 44.4% of 513 cases. Diarrhea occurred with the highest rate (26.3%), but this was controllable. PMID- 2932060 TI - [A comparative study of 5'-DFUR and tegafur in recurrent breast cancer]. AB - A comparative study was performed to evaluate the efficacy and safety of 5'-DFUR and tegafur in recurrent breast cancer. The oral daily dosage of 5'-DFUR was 1,200 mg and that of tegafur was 800 mg, both drugs being administered every day for more than 4 weeks. RESULTS: Cases evaluable for anti-tumor effect were 50 with 5'-DFUR and 38 with tegafur. The response rate was 28.0% (14/50) with 5' DFUR while that with tegafur was 15.8% (6/38). In the cases with no prior fluorinated pyrimidine therapy, 5'-DFUR was significantly superior to tegafur in the response rate. Effective cases determined within 8 weeks numbered 9 out of 50 cases with 5'-DFUR, showing a tendency to be more than those of tegafur, 1 out of 38 cases. This indicates that the appearance of response for 5'-DFUR seems to be faster. The duration of PR tended to be longer with 5'-DFUR than with tegafur. As for the safety, there was no difference between the two groups except for a high incidence of diarrhea in 5'-DFUR. 5'-DFUR tended to be superior to tegafur in its usefulness judged from the angles of efficacy and safety. From the above results, 5'-DFUR can be regarded as having a better efficacy than tegafur for the treatment of recurrent breast cancer, with a fast-appearing anti-tumor effect and a long durability for continuous treatment. PMID- 2932061 TI - Patients with erythema nodosum leprosum lack T-suppressor cells. PMID- 2932062 TI - Subcutaneous sclerosis with fasciitis and eosinophilia after phytonadione injections. AB - We treated a case of subcutaneous sclerosis after phytonadione injections (Texier's disease) that was noteworthy for two associated features: sclerosis with inflammatory infiltrate in the fascia, and blood eosinophilia. A peculiar type of cutaneous sclerosis after phytonadione injections was described in 1972. The sclerosis in that case was first confined to the buttocks, progressively extended to both thighs, and slowly resolved. In the 38 reported cases, neither sclerosis of the fascia nor blood eosinophilia was observed. PMID- 2932063 TI - Histiocytosis-X cells express C3b, C3d, and C3bi receptor (CR1, CR2, and CR3) antigens. PMID- 2932064 TI - Ultrasound study of ovarian and uterine morphology in women with polycystic ovary syndrome before, during and after treatment with cyproterone acetate and ethinyloestradiol. AB - Women with the polycystic ovary syndrome were treated cyclically for two years with an oral oestrogen/progestogen combination of 50 mg of cyproterone acetate and 0.05 mg of ethinyloestradiol. Ovarian volume, ovarian texture and uterine size were monitored by ultrasound before, during and after treatment. Menstrual rhythm, ovulation and the degree of hirsutism were also studied clinically. A significant decrease in the ovarian volume and in the number of cystic areas was observed during treatment. Hirsutism was also markedly improved. Some of these beneficial effects persisted after treatment was stopped. The number of subjects who had regular, ovulatory cycles increased after stopping treatment. Growth of uterine muscle occurred during treatment. PMID- 2932065 TI - [The pathology of Chagas disease in man]. PMID- 2932066 TI - [Echocardiographic findings in Chagas disease]. PMID- 2932067 TI - [M-mode echocardiography in Chagas disease]. PMID- 2932068 TI - Coronary artery dissection after PTCA. PMID- 2932069 TI - Baffle obstruction after the Mustard operation. PMID- 2932070 TI - [The heart in arterial hypertension, factors, overload and ischemia]. PMID- 2932071 TI - [Effects of acidosis and alkalosis on the sarcoplasmic reticulum of the heart]. AB - Some functions of dog cardiac sarcoplasmic reticulum have been studied in acidosis and alkalosis conditions in a range of pH from 6.0 to 7.8. Intravesicular water content at pH 6.0 is 4.7 microliter per mg of protein and diminished to 4 microliter, (15%) at pH 8.0; this correlates with a drop of 13.5% in turbidity. Ca2+-dependent ATPase has an optimal pH of 7.2 and a specific activity of 580 nanomoles of ATP hydrolyzed/min/mg protein. The activity of Basal ATPase or Mg2+-dependent is insensitive to changes of pH. Maximal calcium uptake attains 45.1 +/- 1.4 nanomoles per mg protein between pH 6.0 and 6.6. The accumulated calcium diminished progressively when pH was raised. The rate of calcium transport in steady state shows an optimal pH of 6.7. The calcium transport kinetics constants shows that reticulum has a maximal affinity for calcium between pH 6.87 and 7.02. The maximal velocity for transport diminished progressively between pH 6.1 to 7.16. During the calcium transport process pH is changed from acid to alkaline and the accumulated calcium is release proportionally to the pH increment. This effect shows to be reversible. Calcium accumulation and ATP hydrolysis are uncoupled at pH values higher than 6.6 because to the increase in the rate of calcium release. Values of pK and number of protons per mg of protein that dissociates from ionizable residues are 6.53 and 0.68 respectively for calcium dependent ATPase; 7.09 and 0.60 for calcium transport and 7.41 and 0.39 for calcium release. We conclude that the rate of transport and affinity of cardiac sarcoplasmic reticulum for calcium are optimal between pH 6.8 and 7.0 that is the reported range of intracellular pH of normal cardiac tissue. The data are in close agreement with the fall of contractility in acidosis. It is proposed a calcium release pathway sensitive to pH and different from that of calcium pump, exclusively for entrance. PMID- 2932072 TI - [Prevalence of microscopic coronary atheroma in young adults from Mexico City]. AB - The prevalence of microscopic atheroma in the proximal left anterior descending coronary artery was studied in thirty young males aged 20 to 29 years, living in Mexico City, who died in urban accidents. All of them were either unemployed or labor workers with a socioeconomical status considered to be representative of the majority of young males living in Mexico City. It was found that coronary atheroma was present in 11 of them (33%) with variable degrees of luminal obstruction. In two of them the luminal obstruction was greater than 75%. The prevalence found in this group was significantly different to that found in younger and older males who also died in accidents. Since the prevalence of coronary atheroma was not related to ventricular hypertrophy, valvular or congenital heart disease our findings indicate that in Mexico City as in other geographical regions, coronary atherosclerosis is not an unusual finding in males in the third decade of life, with a low socioeconomical status. PMID- 2932073 TI - [Aortic atresia. Presentation of 7 cases]. AB - The clinical and anatomic findings of 7 patients with aortic atresia were studied. All cases had usual atrial arrangement, atrioventricular and ventriculoarterial concordance. All but one had an intact ventricular septum. All cases presented a hypoplastic left ventricle, and in one, a mitral atresia was found. The clinical diagnosis was made by means of cardiac catheterization and angiocardiography. The presence of a patent ductus arteriosus, the size of the atrial and ventricular septal defects, the diameter of the ascending aorta, pulmonary vascular resistances and right ventricular function are all factors that influence the survival in the patients with aortic atresia. PMID- 2932074 TI - [Crossed atrioventricular connection with straddling of the right atrioventricular valve]. AB - We describe one patient with crossed atrioventricular connection in situs inversus, concordant atrioventricular connection, double outlet right ventricle, and straddling of the right atrioventricular valve. Angiographic features are analyzed, pointing out the importance of selective angiography in order to define the atrioventricular and ventriculoarterial connections. The utility of bidimensional echocardiographic study before cardiac catheterization is emphasized in order to know the associated malformations. PMID- 2932075 TI - [Response of normal children to the treadmill exercise test using the Bruce protocol]. AB - Fifty nine boys and 41 girls underwent exercise stress testing (ETT), utilizing the Bruce protocol. Their mean age was 10 years. They were grouped by sex, age and body surface area. Blood pressure (BP), heart rate (HR) at rest, during exercise and after were monitored as well as the duration of the test and the energy cost. The HR and-BP had a similar linear relationship in both groups during the different stages of the test. The duration of the test expressed in minutes was 11.8 +/- 1.2 in boys and 10.7 +/- 1.2 in girls (P = 0.001). The oxygen consumption (ML/kg/min) was 45.2 +/- 4.9 and 41.9 +/- 4.5 that is equivalent to 12.9 +/- 1.4 and 11.9 +/- 1.2 mets for each group respectively. The group of boys of 6 (9.8) and 14 years of age (13.6) (P = 0.002) and in the girls in the 7 (9.5) and 10 years age group (11.8) P = 0.05. We conclude that 1) The ETT can be done in children safely but was have to take in consideration their age, sex, and body surface area in evaluating the results. 2) This study gives a reference to evaluate children with an without heart disease. PMID- 2932076 TI - [Use of ergometry for evaluating left ventricular function in chronic aortic insufficiency]. AB - Fourteen patients with chronic aortic regurgitation (AR) underwent radionuclide angiography at rest and during supine exercise with ergometric controls. Ten subjects without evidence of heart disease were taken as controls. The behavior of heart rate, ST segment and R wave amplitude were analyzed at peak exercise in relationship with ejection fraction (EF) changes. Abnormal EF, (defined by an increase less than 10%, no change or decrease respect EF control), was present in 9 of 14 patients. Five of 14 patients had normal EF response to exercise defined by an increase of 10% or more than control value. Sensitivity and specificity of heart rate changes at exercise (abnormal: less than 10 beats to MET) to identify abnormal EF were 10% and 100%, respectively. The analysis of ST segment alterations at peak exercise (abnormal more than 2 mm ST depression) to the same objective showed 33% of sensitivity and 80% of specificity. Changes in R wave amplitude (abnormal: increase, no change or decrease less than 22% R wave amplitude at control) at peak exercise had 100% sensitivity and 80% of specificity to identify abnormal EF. Our results suggest that exercise test could be useful to analyze the response to left ventricular function during stress in patients with AR. Changes in R. wave amplitude at peak exercise appeared the best parameter. PMID- 2932077 TI - [The complement system. Normal values and congenital deficiencies in the adult Mexican population]. AB - Five hundred mexican mestizos, healthy blood donors were evaluated regarding the hemolytic activity of their serum, to assess the function of the complement (C) system. One of them was hypocomplementemic and his serum was unable to promote hemolysis by either classical or alternative pathway. It had normal protein concentrations of C3 and C4, as well as immunoreactive C1, C4, C5, C6, C7 and C8, and lytic factor D. Factor B was not recognizable. It is possible that a genetic deficiency linked to genes codifying for class III products of the major histocompatibility complex is responsible for our findings. PMID- 2932078 TI - [Cardiac autonomic neuropathy in the diabetic patient]. AB - The importance of cardiac autonomic neuropathy (CAN) derives from its remarkable frequency and its clinical impact. The clinical features are postural hypotension and resting tachycardia, these abnormalities may be overlooked in a high number of patients asymptomatic. Although rarely life threatening, CAN causes considerable morbidity, which can be ameliorated by its identification and appropriate treatment. Circulatory reflexes were studied in 48 diabetic patients and 14 normal control subjects. Twenty-six of the diabetic patients had normal response. The remaining 22 had evidence of neuropathy and abnormal cardiac response during these tests. Only one patient had postural syncope but he had severe orthostatic hypotension. The others remained asymptomatic. All the control subjects had normal reflexes. Beat-to-beat variation with deep breathing (sinus arrhythmia), carotid body massage and mental stress, were important for the detection of CAN (86, 90 and 90% sensitivity respectively). The Valsalva maneuver and sinus arrhythmia showed 82 and 92% of specificity for the diagnosis of CAN. Our findings suggest that CAN in diabetic patients can be detected by these relatively simple test. We propose a rational approach to the diagnosis. Our method is applicable as a clinical routine examination for cardiac neuropathy. PMID- 2932079 TI - [Phonomechanocardiography in dilated cardiomyopathy]. AB - Twenty seven patients with dilated cardiomyopathy (DCM) were studied by phonocardiography and mechanocardiography. The diagnosis was made in each case by history, laboratory, echocardiogram, hemodynamic study and coronary arteriography. Patients with left complete bundle branch block were excluded. As controls we studied 24 subjects with comparable age an sex. The phonomecanocardiographic records were performed with a Siemens-Elema machine (Mingograph-34) with direct ink recording with electrocardiogram in lead DII, phonocardiogram in mitral focus, and carotid pulse or apexcardiogram (ACG) simultaneously. The following data were assessed: heart rate (HR) electromechanical interval (Q-S2), preejection period of left ventricular contraction (PEP), left ventricular ejection time (LVET), relative ejection period (REP), ratio PEP/LVET (IW), "a" wave of the ACG ("a" wave), rising period of the apex-cardiogram (RPACG), isovolumic relaxation time (IRT), first heart sound intensity (S1I), third and fourth heart sound presence (S3 and S4) respectively. The average values (mean) and their standard deviation for the groups (N) and DCM respectively were: HR (b/m): 67.08 +/- 7.67 and 88.84 +/- 15.31; Q - S2 (msec.): 554.23 +/- 28.37 and 561.35 +/- 30.99; PEP (msec.): 145.13 +/- 17.64 and 194.11 +/- 22.09; LVET (msec): 409.38 +/- 27.68 and 375.54 +/- 28.21; REP (%): 102 +/- 9.27 and 84.78 +/- 8.61; IW: 0.395 +/- 0.078 and 0.72 +/- 0.11; "a" wave (%): 7.37 +/- 2.15 and 19.47 +/- 6.76; RPACG (sec.): 0.093 +/- 0.0015 and 0.143 +/- 0.067; IRT (sec.): 0.094 +/- 0.0012 and 0.105 +/- 0.018.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2932080 TI - [Cardiovascular manifestations in progressive systemic sclerosis]. AB - We studied 20 consecutive patients with progressive systemic sclerosis from the cardiological point of view through non invasive methods. Sixteen (80%) patients had some kind of cardiovascular complications as shown by any of the used methods. a) SYMPTOMS: fourteen (70%) referred some type of cardiac symptoms. b) PHYSICAL EXAMINATION: eleven (55%) had an abnormal cardiac examination and 10 (50%) had arterial hypertension. c) Electrocardiogram: sixteen (80%) were abnormal. Among them, three cases (15%) had bifascicular block, complication considered up till now as rare. d) Cardiac X Ray Series: Fourteen (70%) were abnormal mainly due to pulmonary fibrosis (55%). e) Echocardiogram: 45% of them showed some kind of abnormality. PMID- 2932081 TI - [Alcohol and the cardiovascular system (II). Alcoholic cardiopathy and the possible relation of alcohol to atherosclerosis and arterial hypertension]. PMID- 2932082 TI - [Characterization of coal humic acids for medical use]. PMID- 2932083 TI - [Effect of humic acids on the resorption of sulfaclomide in laboratory rats]. PMID- 2932084 TI - Voice recognition device as a computer interface for motor and speech impaired people. AB - A voice recognition device has been identified as an interface for personal computer control by patients presenting with high-level spinal cord injuries and mild dysarthria. The device enables a person to bypass the traditional keyboard and activate a computer through voice control. The user simply creates templates of a spoken vocabulary in computer memory. The computer then matches real-time spoken words to stored templates for activation. The system has been clinically tested with one 10-year-old boy who has C1-C2 quadriplegia and a 19-year-old man who sustained a C6 spinal cord injury and dysarthria secondary to head injury. Each patient created a vocabulary for computer storage to run educational software packages and games. Accuracy rates for computer speech recognition were measured in multiple practice sessions. Intelligibility of single words produced by the dysarthric speaker was measured also. Both patients activated computer programs through voice control. Recognition rates ranged from 45 to 60% for the first patient, and 79 to 96% for the second patient. A mean success rate for voice recognition across trials with both patients was approximately 80%. The device increased the dysarthric speaker's articulatory precision. Results indicate that the system might be appropriate for rehabilitation programs though further technologic refinement of the device would increase its effectiveness. PMID- 2932085 TI - Cognitive therapy to achieve personal goals: results of telephone group counseling with disabled adults. AB - Physical disability alters a person's lifestyle and can be detrimental in its effects on mood and activity. We describe a counseling program for severely disabled persons who participated in cognitive therapy by telephone. Therapy involved solving problems related to personal dissatisfaction, loneliness, or depression. The treated group reported significantly less loneliness after treatment and were observed by their families to demonstrate more social role skills than the control group. High goal attainment reported by the treated groups was significantly correlated with decreased loneliness, positive changes in social role skills, and family expectations. Treating affective problems with scheduled telephone contact should be further evaluated because of the observed effectiveness and potential for reaching homebound clientele. PMID- 2932086 TI - Rehospitalization and spinal cord injury: cross-sectional survey of adults living independently. AB - A cross-sectional survey of 96 people living independently with spinal cord injuries (SCI) in Eastern Massachusetts shows that 57% had been hospitalized at least once in the year before the survey. Sample means were 1.0 admissions and 16.0 days/person/year. Eight percent of the sample (eight persons) accounted for 22% of admissions and 59% of total hospital days. For those hospitalized, the mean was 1.7 admissions and 45.1 days/person/year. Mean length-of-stay was 34.7 days/admission. Multiple regression analysis shows that three variables appear to be independently related to increased numbers of admissions: self-assessment of health; place of residence; and age (younger respondents at higher risk). One variable is independently associated with total days of hospitalization: leaving home at least once daily (as opposed to less frequently) is associated with lower risk. There were no statistically significant relationships between either numbers of hospitalizations or total days hospitalized and ADL or IADL status, education, employment, medical insurance, household composition, gender, age at onset of disability, time since onset of disability, substance use (alcohol, cannabis, or tobacco), level of SCI lesion, or social supports. PMID- 2932087 TI - [75th anniversary of the Department of Histology of the Leningrad Sanitary Hygienic Medical Institute]. PMID- 2932088 TI - [Pathoanatomical service in World War II in blockaded Leningrad]. AB - Historical materials concerning the work of pathologists in Leningrad under blockade are presented. The characterization of diseases and their course under conditions of the alimentary dystrophy which affected the Leningrad population is given. Problems of blockade hypertension are elucidated. Experience of the pathology service organization in civil hospitals during the war is described, with special reference to the clinico-anatomical correlations. PMID- 2932089 TI - [Tula--city of hospitals (memoirs of a pathoanatomist at a hospital evacuated from the front)]. AB - In spite of all difficulties connected with the war time, the clinico-anatomical conferences were carried out in hospitals and the errors of clinical diagnostics were analyzed. PMID- 2932090 TI - [Primary immunodeficiency state in a child with the pulmonary hypertension syndrome]. AB - A girl aged 2 years and 10 months repeatedly suffered viral (thrice) and bacterial (colitis, salmonellosis, pneumonia 6 times) infections. At an age of 2 years primary pulmonary hypertension was diagnosed. Diagnostic catheterization was performed to exclude a congenital heart disease. The death occurred during the catheterization. An increase of beta-lymphocytes and plasma cells, a reduction of the T-lymphocyte zone were detected in the immunocompetent system during postmortem histological examination. The pathology diagnosis: primary immunodeficiency with a predominant suppression of cell-mediated immunity; hyperplasia of the lymph nodes with their plasmacytization; pneumosclerosis of all lobes of both lungs (a syndrome of primary pulmonary hypertension clinically); hypertrophy of the muscles of both atria and right ventricle, dilation of the heart cavities; acute heart insufficiency. PMID- 2932091 TI - Acute effect of plasma exchange on arterial blood pressure and plasma renin activity. AB - Blood pressure (BP) decreases significantly in patients with immune complex nephritis and hypertension in the course of therapeutic plasma exchange (TPE). To investigate possible underlying mechanisms of this effect, the variations of supine and upright BP and plasma renin activity (PRA) acutely induced by PE (performed by isovolumetric replacement of plasma with 4% albumin in saline solution) were analyzed in six patients. On the average, both supine and upright BP decreased after TPE; however, statistical significance was obtained only for upright systolic BP. Supine and upright PRA did not change significantly, although a clearly blunted response to posture was observed in three patients. The changes of BP induced by TPE were apparently not due to a functional depression of the renin-angiotensin system, since the more marked decrements in BP were observed in the patients with lower basal PRA. PMID- 2932092 TI - Persistent vegetative state. Extension of the syndrome to include chronic disorders. AB - Twenty-nine institutionalized patients had the vegetative state as a sequela of chronic progressive neurologic disorders. During three years, the state was persistent; none improved, ten died. Eight similar patients were reviewed retrospectively post mortem. Eight patients with severe dementia, while acutely ill or sedated, temporarily met the criteria for persistent vegetative state (PVS) but improved when the underlying condition was treated. Abnormalities on electroencephalography or computed tomographic scan are not specific for the PVS. Electroencephalograms were normal in three patients with PVS. The computed tomographic scans showed extensive destruction of the brain parenchyma but were not different from those of severely demented patients without the PVS. The PVS is a feature of the terminal phase of several progressive neurologic disorders. Patients should be treated without excessive intervention. PMID- 2932093 TI - Characterization of the kinetic and regulatory properties of high-affinity Ca2+ ATPase activity in acinar preparations of rat submandibular salivary glands. AB - High-affinity Ca2+-ATPase activity was characterized in the total particulate fraction of acinar preparations from rat submandibular glands. The Ca2+ concentration (as Ca2+-ATP) at half of maximal activity was 82 +/- 17 nM, the Hill coefficient was 2.36 +/- 0.6 and activity reached a steady level at approximately 200 pmol Pi min-1 microgram of membrane protein-1 from 1 to 20 microM Ca2+-ATP. High-affinity Ca2+-ATPase required micromolar concentrations of Mg2+ and was inhibited approximately 60 per cent by the phenothiazine derivative, fluphenazine, but was unaffected by ouabain, Na+, K+, La3+, ruthenium red, oligomycin and added calmodulin. Kinetics of adenosine diphosphate, guanosine triphosphate, uridine triphosphate and inosine triphosphate hydrolysis were similar to those of Ca2+-ATP but p-nitrophenylphosphate was a poor substrate. In the heavy microsomal fraction of whole glands, active Ca2+ uptake (ATP-dependent, oxalate-enhanced and abolished by A23187) was measurable in the absence of added Mg2+, was inhibited by fluphenazine and was stimulated by submicromolar concentrations of Ca2+-ATP. Thus rat submandibular glands contain the enzymic basis of active Ca2+ transport and can actively transport Ca2+. Both activities are stimulated at Ca2+ concentrations typical of the cytosol, appear to be positively cooperative and may be regulated, in part, by calmodulin. PMID- 2932094 TI - Definite vs adjuvant radiotherapy. Comparative effects on lymphocyte subpopulations in patients with head and neck squamous carcinoma. AB - The recent association of alterations in T-lymphocyte subpopulations and impaired cellular immunity prompted an investigation of the effects of radiotherapy (RT) on serial levels of lymphocyte subsets in 30 patients with head and neck squamous carcinoma. Percentage and absolute levels of T3, T4, T6, T8, T10, T11, and Leu 7 cells were measured before, during, and after RT at monthly intervals for six months and compared with levels in 40 normal subjects. Sixteen patients received curative and 14 postoperative adjuvant RT. Before treatment, mean subset levels were similar among the patient and normal groups except for elevated Leu 7 (natural killer) cells in patients with stage I and II disease. There were profound decreases in absolute levels of each subpopulation during and after RT. The percentage of T4 (helper/inducer) cells decreased, whereas that of T8 (cytotoxic/suppressor) and Leu 7 cells tended to increase. Compared with normal values, the mean T4/T8 ratio decreased significantly by six months after RT, when absolute levels of the subsets had rebounded to pretreatment levels in the definitive RT group but remained profoundly decreased in the adjuvant group. The differing recovery patterns suggest that factors other than RT may contribute to persistent immunosuppression following RT. PMID- 2932095 TI - Microprocessor-controlled speech pattern audiometry. Preliminary results. AB - Interactive microprocessor-controlled speech pattern tests making use of high quality synthetic speech have been used to assess the development of subjects' ability to process speech contrasts of increasing complexity, from prosodic contrasts to a 'date-gate' place contrast. These tests have been particularly useful in mapping the development or recovery of subjects functioning at the very first stages of processing ability. Some results obtained with profoundly hearing impaired children and with adults suffering from brain stem disorders are reported, and further applications of speech pattern audiometric techniques are briefly discussed. PMID- 2932096 TI - Breast reconstruction using a rectus abdominis musculocutaneous flap: 5 yr follow up. AB - A 5 yr follow-up of a method of breast reconstruction is presented. It is considered the operation has stood the test of time. PMID- 2932097 TI - Response of the right ventricle to progressive pressure loading in pigs. AB - The purpose of this study was to determine the speed and duration of progressive pressure loading of the right ventricle to systemic pressure levels, which allows right ventricular adaptation without myocardial impairment at rest. In 8 pigs with an average weight of 22 kg progressive right ventricular pressure loading of different speeds and durations was induced with a newly developed constrictor. Pressures in the right atrium, right ventricle, and pulmonary artery as well as angiocardiographic volume parameters of the right ventricle were determined weekly over a period of 4 to 7 weeks. A fast progressive right ventricular pressure increase of 3.4 mm Hg/day during 3 weeks was associated with a 20-30% reduction of ejection fraction and a 100% increase of the end-systolic volume. Increase of end-diastolic pressure was 3 to 5 fold. A slow progressive pressure increase of 1.5 to 2.2 mm Hg/day to 100 mm Hg within 4 to 5 weeks was associated with an increase of the end-diastolic pressure to a level observed in systemic ventricles, while change of ejection fraction and end-systolic volume was minimal. The faster the increase of right ventricular pressure the flatter was the peak systolic pressure/end-systolic volume relationship. It is concluded that in contrast to sudden and fast progressive increase of afterload slow progressive increase of afterload to systemic levels does not impair right ventricular myocardial function. PMID- 2932098 TI - The influence of the genes An1, An2, and An4 on the activity of the enzyme UDP glucose:flavonoid 3-O-glucosyltransferase in flowers of Petunia hybrida. AB - A relation between gene dosage and UDP-glucose:flavonoid 3-O-glucosyl-transferase (UFGT) activity was found in homozygous dominant and recessive parental lines and their F1 progeny for both of the genes An1 and An2. In both F2 crosses, progeny plants could be classified as belonging to groups showing either a low or a medium to high UFGT activity. Test crosses showed that heterozygous and homozygous dominant plants were present throughout the medium- to high-active group. The dosage relation in F2 plants is most probably confounded by the segregation of modifiers. Thermal inactivation experiments indicated that structurally different UFGT enzymes are formed in homozygous dominant lines as well as in lines homozygous recessive for either An1 or An2. Lines homozygous recessive for the gene An4 contain a UFGT with a half-life time at 55 degrees C of less than 8 min, whereas UFGTs from lines homozygous dominant for An4 show a half-life time of 25 min or above, with one exception. This relation was confirmed in the F2 progeny; heterozygotes for An4 showed an intermediate half life time. It is concluded that An4 might be the structural gene for the enzyme; An1 and An2 are both regulatory genes. UFGT activity in flowerbuds of An4/An4 plants seems to be lower than in an4/an4 plants. Anthers of flowers of an4/an4 lines, however, are virtually devoid of UFGT activity. PMID- 2932099 TI - Dietary ethanol and lipid synthesis in Drosophila melanogaster. AB - When cultured on a defined diet, ethanol was an efficient substrate for lipid synthesis in wild-type Drosophila melanogaster larvae. At certain dietary levels both ethanol and sucrose could displace the other as a lipid substrate. In wild type larvae more than 90% of the flux from ethanol to lipid was metabolized via the alcohol dehydrogenase (ADH) system. The ADH and aldehyde dehydrogenase activities of ADH were modulated in tandem by dietary ethanol, suggesting that ADH provided substrate for lipogenesis by degrading ethanol to acetaldehyde and then to acetic acid. The tissue activity of catalase was suppressed by dietary ethanol, implying that catalase was not a major factor in ethanol metabolism in larvae. The activities of lipogenic enzymes, sn-glycerol-3-phosphate dehydrogenase, fatty acid synthetase (FAS), and ADH, together with the triacylglycerol (TG) content of wild-type larvae increased in proportion to the dietary ethanol concentration to 4.5% (v/v). Dietary ethanol inhibited FAS and repressed the accumulation of TG in ADH-deficient larvae, suggesting that the levels of these factors may be subject to a complex feedback control. PMID- 2932101 TI - The effect of medroxyprogesterone acetate on the hepatic drug-metabolizing enzymes in normal and protein-deficient female rats. AB - Effect of depot medroxyprogesterone acetate on the hepatic drug-metabolizing enzymes was studied in female protein-deficient and normal pair-fed rats. Treatment with this drug did not cause any change in organ weight, microsomal protein, and soluble protein yield per gram of tissue in both groups. MPA administration resulted in significant increases in the content of cytochrome P 450 and b5, and activities of benzo[a]pyrene hydroxylase, UDP glucuronosyltransferase, and NADPH-Cyt c reductase in both pair-fed control and protein-deficient rats. However, the content of glutathione and activity of glutathione-S-transferase were not affected appreciably. The present study suggests that MPA treatment induces drug-metabolizing enzymes in liver to almost the same extent in both protein-deficient and normal pair-fed rats. PMID- 2932100 TI - Characterization of a macrophage-derived plasminogen-activator inhibitor. Similarities with placental urokinase inhibitor. AB - Human and mouse macrophages release a fibrinolytic inhibitor after stimulation by endotoxin in vitro. The released mouse inhibitor was indistinguishable in size by molecular-sieve chromatography from an intracellular form (approx. 50 kDa), and both inhibitors blocked urokinase directly as judged by a 125I-plasminogen conversion assay. The intracellular inhibitor was found mostly to dissociate from 125I-urokinase during sodium dodecyl sulphate/polyacrylamide-gel electrophoresis under reduced conditions, but a dodecyl sulphate-stable complex at 65-67 kDa was observed. Because of similarities in the reported size, stability and urokinase binding properties of a placental urokinase inhibitor, the kinetic properties of the two inhibitors were compared. Under the reaction conditions employed (37 degrees C at pH7.4 in the presence of 0.2% Triton X-100), the association rate constants and equilibrium dissociation constants of the two inhibitors were indistinguishable, 3 X 10(5) M-1 X s-1 and 4 X 10(-10) M respectively. These data show that peritoneal macrophages contain a plasminogen-activator very similar to a previously recognized placental inhibitor. Although the inhibitor appears to be a trace protein in macrophages, placental macrophages may account for the accumulation of the inhibitor in placental tissue. PMID- 2932102 TI - Recycling enzymatic assay of NAD--interference by an activator in human erythrocytes. PMID- 2932103 TI - Two-dimensional 1H NMR studies of rat atrial natriuretic factor(1-23). AB - Using a variety of two-dimensional NMR methods, the 1H NMR resonances of rat ANF(1-23) in dimethyl sulfoxide-d6 solution have been assigned. Two-dimensional phase sensitive correlated spectroscopy was used to identify protons that are scalar coupled and were also used to obtain coupling constants (3JNH-alpha CH) in complicated regions of the spectra. Relayed coherence transfer experiments proved useful in identifying the connectivities between the NH and beta-protons of the same amino acid residue. Finally, phase sensitive 2D NOE experiments allowed the identification of protons close in space between adjacent residues, thus providing the sequential assignments as well as conformational information. These preliminary results (chemical shifts, coupling constants, NOEs) were analyzed in terms of possible polypeptide secondary structures and were found to be consistent with a beta-type structure or an averaging of solution conformations (random coil). PMID- 2932104 TI - The effect of the lysosomotropic drug chloroquine on the binding of N-acetyl-beta D-glucosaminidase to mannose-6-phosphate recognizing receptors of rat liver. AB - The binding of N-acetyl-beta-D-glucosaminidase to rat liver receptors was studied in the presence of chloroquine. The association rate constant was not affected in the presence of the drug, while the dissociation rate constant and consequently the equilibrium dissociation binding constant significatively decreased. This results may explain effects of chloroquine on lysosomal enzyme transport found in cultured cells by other authors. PMID- 2932105 TI - Quantitative analysis of intermediate phosphate-oxygen exchange during hydrolyses by ATPases. AB - A simple mathematical model is presented that predicts the paradoxical effect of substrate concentration on the extent of oxygen exchange into the phosphate produced during hydrolyses of nucleotide triphosphates by ATPases in labelled water. The same model also predicts the deviations from Michaelis-Menten kinetics observed at low salt concentrations. PMID- 2932106 TI - Gluco- and mineralocorticoids may regulate the natriuretic effect and the synthesis and release of atrial natriuretic factor by the rat atria in vivo. AB - Adrenalectomy abolished the acute natriuretic effect of ANF which was partially restored to about 50% by combined therapy with gluco- and mineralocorticoids. It is suggested that the lack of effect of ANF may be due to a decreased renal vascular reactivity to the peptide in adrenalectomized animals. Simultaneous administration of Dexamethasone and Deoxycorticosterone acetate to adrenalectomized rats produced a marked increase in immunoreactive ANF in atrial tissue and plasma. The administration of NaCl to these animals produced a relatively lower concentration of atrial ANF and a further increase in plasma ANF. Our results suggest that glucocorticoids may regulate synthesis and release of ANF by the atria and mineralocorticoids may have a permissive role. Furthermore, the presence of steroids is necessary for the NaCl-stimulated ANF release. PMID- 2932107 TI - Enzyme concentration affects the allosteric behavior of yeast phosphofructokinase. AB - The influence of enzyme concentration on the kinetic behavior of yeast phosphofructokinase has been examined. A marked decrease in the ATP inhibition was observed when the enzyme activity was studied in permeabilized cells (in situ) as well as when the kinetic study was carried out with the purified yeast enzyme at a concentration of 120 micrograms/ml as compared to a 100-fold diluted enzyme. A similar result was obtained by adding polyethylene glycol either to a cell free extract or to the diluted pure enzyme to increase the local protein concentration. However, enzyme concentration had no significant effect on the fructose-6-P saturation curve. These results provide evidence that the allosteric behavior of yeast phosphofructokinase is affected by enzyme concentration. PMID- 2932109 TI - Investigation on the substrate specificity of human plasmin using tripeptidyl-p nitroanilide substrates. AB - The hydrolysis of 35 tripeptidyl-p-nitroanilides was studied with human plasmin and the kinetic parameters were determined. The individual contribution of the various side chains to the kinetic parameters was calculated by regression analysis. Considering Km, substrates having Z-D-Ile-Phe-Lys as well as H-D-Ile Phe-Lys sequences were found to be the best, while Bz-Ile-Leu-Lys and pGlu-Leu Lys sequences are the best for kcat. The Km values of substrates protected at N terminus are lower, their kcat values are higher than those of the unprotected ones with the same sequence. PMID- 2932108 TI - Calmodulin inhibitor trifluoperazine selectively enhances cytotoxic effects of strong vs weak DNA binding antitumor drugs in doxorubicin-resistant P388 mouse leukemia cells. AB - Doxorubicin-resistant P388 mouse leukemia cells are cross-resistant to anthracycline and non-anthracycline DNA intercalators as well as to natural and semisynthetic anthracyclines which bind weakly or not at all to DNA. In the presence of a non-lethal concentration of 5 microM trifluoperazine cytotoxic effects of the strong DNA binding drugs actinomycin-D, mitoxantrone and m-AMSA were enhanced less than 2 fold in doxorubicin-sensitive cells and up to 50 fold in doxorubicin-resistant cells. Additionally, trifluoperazine induced a greater than 2-fold enhancement in the cytotoxic effects (but not accumulation and retention) of the strong DNA binder N,N-dimethyladriamycin-14-valerate only in doxorubicin resistant cells. In contrast, cell kill, drug accumulation and retention in P388/S and P388/DOX cells treated with the weak DNA binders N-benzyl adriamycin-14-valerate and 7(R)-O-methylnogarol, and DNA-nonbinding N,N dibenzyldaunorubicin was similar with or without trifluoperazine treatment. The study demonstrates that the calmodulin inhibitor trifluoperazine induces a specific and marked enhancement in the cytotoxic effects of strong vs weak DNA binding antitumor drugs in doxorubicin-resistant cells. PMID- 2932110 TI - Identification of a cDNA clone in lambda gt11 for the transacylase component of branched chain ketoacid dehydrogenase. AB - Two cDNA clones for the transacylase protein of the branched chain ketoacid dehydrogenase complex [E.C. 1.2.4.4] have been isolated from a human fetal liver cDNA expression library in lambda gt11 using antibody selection. By selective antibody elution from nitrocellulose filters containing the fusion proteins, it was determined that these inserts represent the transacylase protein. These data support the hypothesis that this protein is synthesized in the cytosol on transcripts independent of the other proteins of the branched chain ketoacid dehydrogenase complex. PMID- 2932112 TI - Induction of mutation in vitro in phage phi X174 am3 by N4-aminodeoxycytidine triphosphate. AB - When phi X174 am3-phage-infected E. coli is treated with N4-aminocytidine, reversion of the phage to the wild type is efficiently induced. The mechanism of this reversion is considered to consist of metabolic conversion of N4 aminocytidine into its deoxynucleoside 5'-triphosphate followed by incorporation of the nucleotide into the replicating phage DNA, thereby causing AT-to-GC transition at the am3 locus. The second half of this mechanism has now been experimentally proved, using an in vitro mutagenesis system. Thus, by nick translation, N4-aminodeoxycytidine 5'-triphosphate was incorporated into the replicative form of phi X174 am3 DNA, and the DNA was used to transfect CA++ treated E. coli HF4714 (sup+). The reversion frequency of the phage produced was up to one-order of magnitude greater than that of the control in which the nick translation had been done without the addition of N4-aminodeoxycytidine triphosphate. This nucleotide analog may be useful as a reagent for in vitro site directed mutagenesis. PMID- 2932111 TI - Linear relationship between diphosphorylation of 20 kDa light chain of gizzard myosin and the actin-activated myosin ATPase activity. AB - The addition of large amounts of myosin light chain kinase to the reconstituted gizzard actomyosin shows diphosphorylation of 20 kDa myosin light chain. Accompanying diphosphorylation, the actin-activated myosin ATPase activity was also enhanced. The extent of diphosphorylation and the myosin ATPase activity were clearly demonstrated to be in a linear relationship. From the time course experiment, the conversion of monophosphorylated light chain into one which was diphosphorylated seemed to be a sequential process. Moreover, analyzing phospho amino acid by using a two-dimensional electrophoresis technique revealed that monophosphorylated light chain contained phosphoserine and diphosphorylated one contained phosphothreonine in addition to phosphoserine. PMID- 2932113 TI - Reaction of phenylglyoxal with chicken gizzard myosin. AB - Modification of chicken gizzard myosin with phenyl[2-14C]-glyoxal inhibited the K+-ATPase (ATP phosphohydrolase, EC 3.6.1.32) activity as a function of time. During the 2.5 and 15 min interval 3.2 mol of the reagent were incorporated per 4.7 X 10(5) g protein and the K+-ATPase activity was 50% inhibited. Phenylglyoxal reacted with arginine residues of gizzard myosin in a mol ratio of two to one, phenylglyoxal to arginine as determined spectrophotometrically. The modification was limited to the subfragment 1 heavy chain and rod-like regions and none of the light chains were lost. The inhibition of the ATPase activity occurred when the subfragment 1 region was modified predominantly. The same results were obtained when the myosin was phosphorylated and then incubated with phenylglyoxal. Substrate MgATP2- or MgADP enhanced the inactivation of gizzard myosin; there was an increase in the incorporation of the reagent and a change in the distribution into the heavy chains. Approx. 0.5 mol of the nucleotide was bound to 4.7 X 10(5) g of phenylglyoxal myosin. Conformational changes, induced by these modifications, were responsible for the inhibition of enzymic activity. Arginine residues of gizzard myosin are necessary for the maintenance of the ATPase activity of this contractile protein. PMID- 2932114 TI - Effect of parthenin on mitochondrial oxidative phosphorylation. AB - The sesquiterpene lactone, 'parthenin' the toxic principle of the allergenic weed Parthenium hysterophorus, inhibited 'state 3' respiration and stimulated 'state 4' respiration in rat liver and kidney mitochondria as well as ATPase activity in the presence of Mg2+ ions. These properties indicate that the toxic action of parthenin may be related to its interference with oxidative phosphorylation. PMID- 2932115 TI - Role of alcohol dehydrogenase in the swift increase in alcohol metabolism (SIAM). Studies with deer mice deficient in alcohol dehydrogenase. AB - Previous studies have shown that rates of ethanol metabolism increase markedly 2 4 hr after the administration of ethanol in rats and in four inbred strains of mice. This phenomenon, called the swift increase in alcohol metabolism (SIAM), also exists in humans. To determine whether alcohol dehydrogenase (ADH) is necessary for the SIAM response, we compared ethanol metabolism in two strains of the deer mouse, Peromyscus maniculatus. One strain lacks alcohol dehydrogenase (ADH-negative), whereas the other strain has normal ADH levels (ADH-positive). Rates of ethanol elimination were determined after a single intraperitoneal injection of ethanol at different doses (0.5 to 3.0 g/kg) and also after both strains were exposed to various levels of ethanol vapor for 4 hr. The ADH positive strain exhibited up to a 72% increase in the rate of ethanol elimination after exposure to ethanol vapor compared to the ethanol-injected controls. In contrast, treatment with ethanol vapor did not alter rates of ethanol elimination in the ADH-negative strain. These data demonstrate clearly that ADH is required for SIAM in the deer mouse. In addition, in both the ADH-positive and the ADH negative strain, rates of ethanol elimination increased in both the ethanol injected and vapor-treated groups 2- to 3-fold as the dose of ethanol was increased from 100 to 500 mg/100 ml. Thus, it is concluded that this "concentration effect" of ethanol on rates of ethanol metabolism does not involve ADH in the . deer mouse. PMID- 2932116 TI - The roles of the hepatocellular redox state and the hepatic acetaldehyde concentration in determining the ethanol elimination rate in fasted rats. AB - Ethanol administration (2 g/kg i.p.) to fasted male Wistar rats caused, on average, a 64% decrease in the cytosolic free NAD+:NADH ratio and a 41% decrease in the mitochondrial free NAD+:NADH ratio measured 90 min after ethanol was injected. Treatment of animals with either Naloxone (2 mg/kg i.p.) 1 hr after ethanol or 3-palmitoyl-(+)-catechin (100 mg/kg p.o. 1 hr before ethanol) prevented these ethanol induced redox state changes, without affecting the ethanol elimination rate or the hepatic acetaldehyde concentration measured at 90 min after ethanol administration. The thiol compounds cysteine and malotilate (diisopropyl-1,3-dithiol-2-ylidene malonic acid) significantly lowered the hepatic acetaldehyde concentrations measured at 0.75, 1.5 and 6.0 hr after ethanol, and caused a 29% and 12% increase respectively in the ethanol elimination rate, without affecting the ethanol induced alterations in the NAD+:NADH ratio. Pretreatment of animals with the aldehyde dehydrogenase inhibitor, cyanamide (1 mg/kg or 15 mg/kg p.o. one hour before ethanol), caused increases of up to 23-fold in the hepatic acetaldehyde level, without influencing the cytosolic NAD+:NADH ratio in ethanol dosed rats, while significantly reducing the ethanol elimination rate by up to 44%, compared with controls. These results suggest that ethanol oxidation by cytosolic alcohol dehydrogenase may be regulated in part by the hepatic acetaldehyde concentration achieved during ethanol metabolism rather than NADH reoxidation, either to supply NAD for the dehydrogenase, or to reduce inhibition of the enzyme by NADH, being a rate limiting factor in ethanol metabolism in fasted rats. PMID- 2932117 TI - Properties of a Ca2+ and Mg2+ stimulated ATPase in the rat caudate nucleus. AB - Adenosine triphosphatase (ATPase) activity which could be stimulated maximally by either Ca2+ or Mg2+ was identified in a synaptosomal fraction from rat brain caudate nucleus. The thermodynamic properties of the Ca2+ and Mg2+ stimulated enzymes were similar to each other. Oligomycin, sodium azide and dinitrophenol had no significant inhibitory effects on stimulation by either cation. In vitro incubation of the ATPase with cis- or trans-flupenthixol, chlorpromazine or trifluoperazine, but not with haloperidol, significantly inhibited stimulation by either cation. The DA receptor agonist 2-amino-6,7-dihydroxy-1,2,3,4 tetrahydronaphthalene (ADTN) inhibited stimulation of the enzyme by either cation, while d-amphetamine, SKF 38393, pergolide and LY-171555 had no significant effects. Nomifensine at 10(-3) M inhibited the cation stimulation by about 33%. In vivo administration of dopamine (DA) receptor antagonists (haloperidol, cis- and trans-flupenthixol, spiperone, chlorpromazine and trifluoperazine) and the agonist apomorphine neither inhibited nor stimulated ATPase activity. It appears from these data that the ATPase activity is not under DA receptor modulation. In addition, our tentative conclusion is that one enzyme is involved, because both Ca2+ and Mg2+ produced similar maximal stimulations, the activities as a function of temperature were similar, the enzyme could not be further stimulated with Ca2+ after maximal stimulation by Mg2+ (and vice versa), and the behaviour of the ATPase activity to all drugs tested was similar. PMID- 2932118 TI - Alcoholic muscle disease. AB - Histopathological abnormalities of muscle are common in chronic alcoholics and can be classified into the rare acute myopathy, with myonecrosis, and the much more common chronic myopathy, with a selective atrophy of type II muscle fibres (particularly IIb fibres). The patients may often be asymptomatic and, except for florid cases of acute rhabdomyolysis, clinical features do not help to distinguish the two. Serum creatine kinase activity is an insensitive guide to the presence of the muscle abnormalities. These abnormalities cannot be adequately explained by co-existing alcoholic liver disease, malnutrition or peripheral neuropathy, and probably represent the result of direct toxicity to the muscle fibres. Acute myopathy may occur as a result of damage to cell membranes although intracellular phosphate deficiency has also been proposed as a crucial factor. Atrophy of type II fibres occurs in other metabolic myopathies and its development in chronic alcoholism could represent the result of metabolic or endocrinological derangement induced by ethanol. Alternatively, direct toxicity to muscle cell pathways of carbohydrate catabolism or fatty acid oxidation may occur. Previous suggestions of enhanced muscle breakdown in chronic alcoholics is contested by recent work and reduced protein synthesis may be of more pathogenic importance. Abstention from alcohol reverses the muscle abnormalities. PMID- 2932119 TI - Genetic and environmental factors in the individual susceptibility to the development of alcoholic liver disease. AB - Although there is a dose-response relationship between alcohol consumption and liver damage, less than one-third of alcoholics develop alcoholic liver disease (ALD). This individual susceptibility to the development of ALD may be explained by genetic and environmental factors. Of the genetic factors, female sex is clearly a significant risk factor, HLA status is probably important but further studies are needed, abnormalities in alcohol metabolism have not been shown to be of primary pathogenic importance and the plethora of immunological disturbances reported appear to be mere epiphenomena. Of the environmental factors, no consistent evidence attests to the significance of hepatitis B viral infection in the susceptibility to developing ALD. PMID- 2932120 TI - Nutrition and the biochemical pathology of the alcohol-induced liver injury. AB - The possible role of nutritional disturbances in the biochemical pathology of the alcohol-induced liver injury is briefly discussed. Nutritional factors could influence a number of hepatotoxic effects of ethanol and it is therefore suggested that, although ethanol itself is capable of causing almost all its hepatotoxic effects, the possible contribution of any associated nutritional disturbances to liver injury in chronic alcoholism deserves careful consideration. PMID- 2932121 TI - Effect of Lamaze childbirth preparation on maternal plasma beta-endorphin immunoreactivity in active labor. AB - Previous studies have documented a reduction in plasma beta-endorphin levels with the use of various analgesic techniques in labor, such as segmental epidural anesthesia or intrathecal morphine. The Lamaze method of childbirth preparation, which has been found to reduce the need for medication during childbirth and to decrease the subjective perception of pain during labor and delivery, has not been studied in this regard. In this study plasma beta-endorphin immunoreactivity levels were measured during the active phase of labor in 26 patients who had Lamaze classes and in 28 patients who did not have Lamaze classes. The Lamaze group had significantly lower plasma beta-endorphin immunoreactivity (37.2 vs. 68.5 pg/ml; P less than 0.001) and significantly shorter first stages of labor (8.28 hrs. vs. 9.86 hrs; P less than 0.02). It can be theorized that both lower beta-endorphin immunoreactivity and shorter labor in patients in the Lamaze group were related to the reduction of fear, tension, and the emotional stress of labor. PMID- 2932122 TI - [New recommendations in the treatment of genital infections caused by Neisseria gonorrhoeae in Puerto Rico]. PMID- 2932123 TI - [Equity and health care in Latin America. Principles and dilemmas]. PMID- 2932125 TI - [Training of human resources for health administration]. PMID- 2932124 TI - [Patient referral in a regional health unit in Colombia]. PMID- 2932126 TI - [Salmonella serotypes identified in Mexico between 1974 and 1981]. PMID- 2932127 TI - [Medical care and infant mortality in Chile]. PMID- 2932128 TI - [Bacteriologic and serologic aspects of streptococcal pharyngitis in Mexico City]. PMID- 2932129 TI - [Rapid determination of blood alcohol with the ADH/REA method: method comparison and evaluation]. PMID- 2932130 TI - [Characterization of activated rosette-forming lymphocytes by monoclonal antibodies]. PMID- 2932131 TI - A mouth-controlled appliance for severely physically handicapped patients. PMID- 2932132 TI - Effect of percutaneous transluminal coronary angioplasty on arrhythmias complicating angina. AB - Four patients who had stenosis of a single major coronary artery which was treated by percutaneous transluminal coronary angioplasty are described. Three had exercise induced myocardial ischaemia complicated by ventricular tachycardia, fibrillation, and sinus bradycardia, respectively. Asystole developed in a fourth patient who had spontaneous chest pain. After successful percutaneous transluminal coronary angioplasty these arrhythmias did not recur spontaneously or on treadmill exercise testing. Percutaneous coronary angioplasty can be effective in preventing arrhythmias complicating acute myocardial ischaemia secondary to stenosis of a single major coronary artery. PMID- 2932133 TI - Percutaneous balloon valvuloplasty for pulmonary valve stenosis in infants and children. AB - Pulmonary valve stenosis was relieved by balloon dilatation during cardiac catheterisation on 27 occasions in 23 infants and children aged 7 days to 12 years, median 31 months (three aged less than 2 weeks). Pulmonary valve diameter was estimated by cross sectional echocardiography to assist in the choice of balloon size. Before dilatation the right ventricular systolic pressure ranged from 41 to 190 (median 92) mm Hg and was suprasystemic in 10 patients. There were significant reductions in the ratio of right ventricular to systemic systolic pressure and pulmonary systolic pressure gradients immediately after balloon dilatation. Twelve patients underwent recatheterisation (11 at six months and one at one week after balloon dilatation), which showed further improvement with significant reductions in right ventricular pressure or pulmonary valve gradient or both, particularly in the patients with the least satisfactory initial results. This improvement was attributed to resolution of the obstruction at infundibular level. Repeat pulmonary valve dilatation was successfully performed in four patients who had poor results after initial dilatation. Balloon pulmonary valvotomy appears to provide good short term and medium term relief of pulmonary valve stenosis and may obviate the need for surgery in many cases. An apparently poor immediate haemodynamic result does not preclude a good longer term result. PMID- 2932134 TI - Asymmetric septal hypertrophy and hypothyroidism in children. AB - Any echocardiographic study of two children with hypothyroidism demonstrated the presence of asymmetric septal hypertrophy. One child died aged 11 months, and pronounced thickening of the interventricular septum was confirmed at necropsy. There was also hypertrophy of the left ventricular free wall. Histological examination showed only slight muscle fibre disarray, but there was striking vacuolation and hypertrophy of muscle fibres. In the second case, a child aged five years, the asymmetric septal hypertrophy disappeared after 18 months' treatment with L-thyroxine. Furthermore, other indices of myocardial function also returned to normal. The mechanism producing asymmetric septal hypertrophy in hypothyroidism is unknown. These are the youngest cases in which this association has been reported. PMID- 2932135 TI - Cardiac hypertrophy, hypertrophic cardiomyopathy, and hyperparathyroidism--an association. AB - Left ventricular hypertrophy (symmetric, asymmetric, or hypertrophic cardiomyopathy) is an almost invariable accompaniment of primary hyperparathyroidism. Five of 18 patients with hypertrophic cardiomyopathy had raised serum concentrations of parathyroid hormone with normal serum calcium concentrations. Left ventricular hypertrophy did not occur in any of the six patients with hypercalcaemia alone. These relations suggest that parathyroid hormone rather than a rise in the extracellular calcium concentration is associated with a spectrum of left ventricular hypertrophy. All patients with increased circulating parathyroid hormone concentrations should have echocardiographic examination of the left ventricle. Conversely, parathyroid hormone concentrations should be measured in all patients with left ventricular hypertrophy from an unknown cause, especially those with hypertrophic cardiomyopathy. PMID- 2932136 TI - Interaction of midazolam with two non-depolarizing neuromuscular blocking drugs in the rat in vivo sciatic nerve-tibialis anterior muscle preparation. AB - Studies of the possible interactions between the water-soluble benzodiazepine, midazolam, and two non-depolarizing neuromuscular blocking drugs, vecuronium and tubocurarine, were performed in the rat in vivo sciatic nerve-tibialis anterior muscle preparation. Midazolam 0.5 and 5 mg kg-1 caused 17% and 34% depression of the twitch height, respectively, once a steady-state blockade of the twitch height had been induced by vecuronium. The potentiation of the tubocurarine steady state blockade by midazolam 5 mg kg-1 was quantitatively equal to that of vecuronium, but was slower in onset. The buffer solvent of midazolam 5 mg kg-1 did not change the steady-state blockade of vecuronium. Midazolam 5 mg kg-1 caused a shift to the left of the cumulative dose-response curves of vecuronium. PMID- 2932137 TI - A place for ipratropium bromide in the treatment of severe acute asthma. AB - Twenty-four consecutive patients admitted to hospital with severe acute asthma were studied. Eleven were given 10 mg salbutamol by nebulizer followed 2 hours later by 500 micrograms of nebulized ipratropium bromide. These patients had a greater response in PEFR than 13 patients given two doses of 10 mg salbutamol 2 hours apart. PMID- 2932138 TI - A comparison of three high doses of ipratropium bromide in chronic asthma. AB - We have performed a double-blind crossover study in nine patients with stable chronic asthma, in order to evaluate the effects of three doses of the anticholinergic bronchodilator ipratropium bromide (80 micrograms, 200 micrograms and 400 micrograms) given by metered dose inhaler. These doses are larger than the recommended dose (40 micrograms). All three doses of the drug produced significant bronchodilation from 15 minutes to 5 hours. Some small but statistically significant differences were found in favour of the 200 micrograms and 400 micrograms doses when compared with the 80 micrograms dose and the duration of action of the 400 micrograms dose was longer than that of 200 micrograms dose. The clinical usefulness of these small differences remains to be assessed. PMID- 2932139 TI - A report of two long-surviving cases of pulmonary lymphangioleiomyomatosis and the response to progesterone therapy. AB - Two cases of pulmonary lymphangioleiomyomatosis, with survival between 12 and 28 years are described. Both were treated with medroxyprogesterone acetate with a slight initial improvement in both lung function and exercise tolerance, and no further deterioration during the period of follow-up of 10-20 months. The results are discussed and other reports of hormonal treatment of this rare condition are reviewed. PMID- 2932140 TI - Training and education approaches for parents of children with special needs. AB - This is a review of attempts made to involve and to train parents in the endeavour of helping their children with special needs. The reasons for parent involvement are discussed, before describing and contrasting the variety of theoretical orientations and parenting skills that have been considered in this work, and the influences of parent and child characteristics. Detailed consideration is given to the methods used in training and their effectiveness. Although parent involvement can be said to be of value, more effort is required in terms of careful conceptualization and more elaborate multivariate research before definite answers may be provided for many of the issues raised. PMID- 2932141 TI - Echocardiography in the investigation of anterior abdominal wall defects in the fetus. AB - Of 20 pregnancies referred for fetal echocardiography with a diagnosis of anterior abdominal wall defect, congenital heart disease was present in eight of the 17 with exomphalos and in none of the three with gastroschisis. Four of these eight affected pregnancies were terminated because trisomy 18 was diagnosed, of the remaining four, only one baby survived infancy. We conclude that ultrasound investigation of the fetal heart is an important part of the diagnostic assessment of anterior abdominal wall defect if an accurate prognosis and appropriate obstetric management are to be provided. PMID- 2932142 TI - Subphrenic and mediastinal abscess formation: a complication of Ludwig's angina. AB - A fatal case of cervical cellulitis is described in which mediastinal and subphrenic abscesses formed. Subphrenic abscess formation is a previously unrecorded complication of oro-pharyngeal infection. The anatomical pathways involved in the spread of infection from the neck to the abdomen and the difficulties in obtaining an airway in such a case are discussed. PMID- 2932143 TI - Lingual haematoma leading to upper airway obstruction. AB - A case is reported in which upper airway obstruction occurred in a patient following suturing of his lacerated tongue under local anaesthesia and the subsequent development of a large lingual haematoma. PMID- 2932144 TI - Human ameloblastomas in vitro: light microscopical and ultrastructural observations. AB - The light microscopical and ultrastructural morphology in vitro of one case each of human plexiform, follicular and acanthomatous ameloblastoma are described. Ultrastructural analysis of cultured tumour cells revealed that the main cell type growing in vitro displayed morphological features typical of columnar cells or preameloblast-like cells of ameloblastomas. Irrespective of histological type all cases showed indistinguishable in vitro light microscopical and ultrastructural morphology. These findings strongly suggest that the columnar cell type accounts for the main proliferative capacity of ameloblastomas in vitro and most likely also in vivo. PMID- 2932145 TI - Ameloblastomas of the jaws: radiological diagnosis and follow-up. AB - Eleven of 57 tumours and cysts (19 per cent) seen at two major centres over a 4 year period were ameloblastomas, primary in eight and recurrent in three. Computed Tomography (CT) was the most sensitive imaging technique for detecting ameloblastomas. The radiological features were distinctive maxillary and mandibular pathology in primary cases and soft-tissue, maxillary sinus and asymmetrical deep tissue involvement in both primary and recurrent ameloblastomas. Following surgery and pathological confirmation, serial scans were combined with periodic clinical re-evaluation. We identified clinically occult recurrences in two cases and confirmed a clinically-suspected recurrence in one on the basis of the CT findings. Our protocol appears efficacious and is suggested for the necessary long-term follow-up in all pathologically verified ameloblastomas. PMID- 2932146 TI - Lack of tumour potentiating effect of cryosurgery in hamster cheek pouch after short term carcinogen exposure. AB - Hamster cheek pouch was treated with the topical carcinogen DMBA for 2, 4 or 6 weeks. Cryosurgery to part of the treated area did not produce any alteration in subsequent tumour development. This contrasted with previous studies where cryosurgery following 8 weeks of DMBA application potentiated subsequent tumour development. PMID- 2932147 TI - Traumatic (eosinophilic) granuloma of oral soft tissues: a report of two cases with pseudo-lymphomatous features. AB - Two cases originally diagnosed as extra-nodal lymphomas occurring in lingual and buccal mucosa which subsequently were reclassified as variants of traumatic granuloma are reported. One case may have been associated with Epstein-Barr virus infection. Extra-nodal lymphoma in such sites is very uncommon and the possibility of traumatic granuloma with a pseudo-lymphomatous appearance must be considered when making such a diagnosis. PMID- 2932148 TI - A mucoepidermoid tumour of the tongue. AB - A case of mucoepidermoid tumour arising in minor salivary glands of the tongue and assessed histologically to be of high-grade malignancy is described. The diagnostic difficulties involved in distinguishing the neoplasm from a squamous cell carcinoma are considered. From published figures it would appear that salivary gland neoplasms in the tongue are much more likely to be malignant than benign. PMID- 2932149 TI - Peripheral squamous odontogenic tumour. AB - Squamous odontogenic tumour (SOT) is a rare, benign epithelial tumour of odontogenic origin. A recurrent case of SOT with peripheral occurrence is described. In 1971, a tumour from the anterior maxillary palatal mucosa of an 11 year-old female was excised. In 1984, when the patient was 24 years old, a recurrent tumour was found in the same area. The histopathological appearance of the lesion, which was found to be identical with the primary tumour, was that of an SOT. Both the clinical and radiographic features supported the extra-osseous involvement of both tumours. The SOT is further evaluated and its origin is discussed. PMID- 2932150 TI - An unusual epithelial neoplasm of gingiva resembling the keratoacanthoma. AB - An unusual, tumour-like mass protruding from labial and palatal gingivae and surrounding the unerupted canine in a 12-year-old child is described. Clinically, the lesion was felt to be aggressive but histologically, the most likely diagnosis was keratoacanthoma, probably of the nodulovegetating type. Following excision of the mass, healing has been uneventful. Whether or not the histological diagnosis of keratoacanthoma is accepted, rather than an unusual odontogenic neoplasm, this case illustrates the existence of an entity comprising well-differentiated islands and cysts of squamous epithelium with a rapid growth pattern. PMID- 2932151 TI - Warty dyskeratoma of the oral mucosa. AB - A case of oral warty dyskeratoma is presented and the literature is reviewed in brief. While warty dyskeratoma of the oral mucosa is rare, it appears to exhibit a variability of clinical appearance and to have a special predilection for keratinised mucosae exposed to friction and mechanical stress. PMID- 2932152 TI - An unusual presentation of oral syphilis. AB - A case of late, non-infectious, gummatous syphilis presenting with intra-oral arterial haemorrhage in an 81 year-old lady is described. PMID- 2932153 TI - The use of sutures in the mouth. AB - The purpose of this communication is to establish a case for a more critical review of the indications for the use of sutures in oral surgery. Observations are made on the underlying principles of surgery and, where appropriate, modifications to suit some standard surgical techniques including apicectomy are suggested, which will reduce both the post-operative inconvenience for the patient and the indications for suturing. The case is supported by a retrospective review of the sutures used in a consecutive series of 149 oral surgery patients admitted to hospital for operation under general anaesthesia. PMID- 2932154 TI - X-ray analysis of structural changes induced by reduced nicotinamide adenine dinucleotide when bound to cysteine-46-carboxymethylated liver alcohol dehydrogenase. AB - The structure of the complex between Cys-46-carboxymethylated horse liver alcohol dehydrogenase (CM-LADH) and reduced nicotinamide adenine dinucleotide (NADH) has been determined by X-ray analysis. The complex represents NADH binding to the orthorhombic, "open" conformation of the enzyme. Coenzyme binding here induces a local structural change in the peptide loop 293-297, but there is no domain rotation, as observed for the "closed" conformation of the protein. This local movement of a few residues in the loop is sufficient to trap the nicotinamide ring of NADH within the active-site area close to a productive binding position. The carboxymethyl group on the zinc ligand cysteine-46 is oriented between the pyrophosphate bridge of NADH and the guanidinium group of arginine-369 and can occupy this position because the coenzyme binding cleft remains open and unchanged upon coenzyme binding. The zinc coordination sphere is distorted, and the position of the metal atom is shifted 1 A compared to native unliganded LADH. The distance between the zinc ion and the sulfur of the alkylated cysteine residue is of the order of 3 A. Alkylation experiments were performed at 0.15 and 10 mM iodoacetate, and peptide maps were examined. Gentle treatment with reagent yields an enzyme product which is substituted at only one of the two zinc binding sites per subunit of LADH (Cys-46). This enzyme species maintains its structural integrity; it binds coenzyme which induces conformational changes resolved into two steps. Thus, in addition to the orthorhombic complex, a crystalline NADH complex in the closed conformation of CM-LADH was obtained. These crystals showed enzymic activity, and single crystals were analyzed with microspectrophotometric methods. Formation of the stable crystalline abortive complex between CM-LADH NAD+ and 4-trans-(N,N-dimethylamino)cinnamaldehyde (DACA) could be observed upon addition of excess aldehyde to the closed complex of CM-LADH-NADH. The CM-LADH NAD+-DACA complex is characterized by an intense absorption band with a lambda max at 456 nm which corresponds to a shift in the spectrum of free DACA of approximately 60 nm. At the higher concentration of iodoacetate, three of the cysteine ligands to the second zinc atom (Cys-100, -103, and -111) are alkylated in addition to Cys-46. This enzyme product rapidly denatures and cannot be crystallized under our conditions. This is an experimental indication that the intact noncatalytic zinc binding site contributes to the structural stability of the protein. PMID- 2932156 TI - Second-derivative infrared spectroscopic studies of the secondary structures of bacteriorhodopsin and Ca2+-ATPase. AB - The resolution of minor amide components in the infrared spectra of membrane proteins has, in the past, been limited by the small differences in frequency compared to the large half-widths of the bands that are assigned to different secondary conformations. Here, second-derivative calculations are used to resolve the relatively weak bands that are associated with the beta-sheet conformation and the vibrations of some amino acid side chains in the infrared spectra of bacteriorhodopsin and Ca2+-activated adenosine-5'-triphosphatase (Ca2+-ATPase). The spectra presented indicate that bacteriorhodopsin in the purple membrane contains an appreciable amount of beta structure in addition to the predominant alpha II-helical structure. Both sarcoplasmic reticulum and purified Ca2+-ATPase in native lipids contain alpha-helical and random coil conformations together with a small amount of beta structure. In 1,2-dimyristoyl-sn-glycero-3 phosphocholine (DMPC) Ca2+-ATPase adopts a secondary conformation similar to that in the sarcoplasmic reticulum, and this structure is unaffected by the phospholipid phase transition. A shift to a predominantly random coil conformation is associated with solubilization of both bacteriorhodopsin and Ca2+ ATPase in 20% Triton X-100. Second-derivative analysis of the carbonyl stretching vibrations of DMPC bilayers indicates that below the phase-transition temperature (Tm) both bacteriorhodopsin and Ca2+-ATPase perturb the interface region such that the sn-2 carbonyls adopt a conformation similar to the sn-1 carbonyls. Above Tm, these integral proteins have no effect on the static order of the interface region, and the conformational inequivalence of the sn-1 and sn-2 carbonyls is similar to that found in a pure lipid bilayer. PMID- 2932155 TI - Dissociation of the receptor for immunoglobulin E in mild detergents. AB - We previously showed that, in the absence of phospholipids, exposure of the tetrameric receptor for immunoglobulin E to mild detergents dissociates the intact beta chain and two gamma chains from the alpha chains. Having developed a practical method for assaying the dissociation, we have now explored a variety of different detergents, detergent concentrations, temperatures, times, salts, pHs, and other factors that influence the detergent-induced dissociation. Our findings should be useful for optimizing the stability of the receptor and for future studies on recombination of the subunits. The data suggest the following: (1) The critical perturbant is micellar detergent. (2) Unlike solubilization of membranes, where a molar ratio of micellar detergent:lipid of 2 is adequate, dissociation of the receptor is incomplete even at molar ratios of micellar detergent:receptor of greater than 10(5) and may be limited by a reversible component. (3) Detergents that are best for solubilizing membranes are also best for dissociating the receptors. (4) The latter observation and other data implicate bound lipid as stabilizing the receptor. Our findings may be applicable to the study of interactions between membrane proteins in general. PMID- 2932157 TI - Factors influencing interaction of phosphorylated and dephosphorylated myosin with actin. AB - The influence of various factors on the interaction of phosphorylated and dephosphorylated myosin with actin was examined. It was found that the difference between the values of specific activity of the two myosin forms of actin stimulated Mg2+-ATPase is affected by changes in KCl, MgATP and actin concentration. The effect of increased pH on the differences in the rate of ATP hydrolysis by actomyosin containing phosphorylated myosin as compared with that of the dephosphorylated one, observed in the presence of EGTA, is abolished by addition of Ca2+. Tropomyosin strongly inhibits the actin-stimulated Mg2+-ATPase of phosphorylated myosin (by about 60%). The tropomyosin-troponin complex and native tropomyosin lowered the rate of ATP hydrolysis by actomyosin containing both phosphorylated and dephosphorylated myosin by about of 60% of the value obtained in the absence of those proteins. These results indicate that the change of negative charge on the myosin head due to phosphorylation and dephosphorylation of myosin light chains modulates the actin-myosin interaction at different steps of the ATP hydrolysis cycle. Phosphorylation of myosin seems to be a factor decreasing the rate of ATP hydrolysis by actomyosin under physiological conditions. PMID- 2932158 TI - Circular dichroism studies on synthetic signal peptides. AB - Circular dichroism studies on synthetic peptides corresponding to the signal sequences of chicken lysozyme and Escherichia coli proteins, lambda-receptor and lipoprotein, have been carried out in trifluoroethanol. The peptides, (CH3)3-C-O CO-Thr-Leu-Lys-Lys-Leu-Pro-Leu-Ala-Val-Ala-Val-Ala-Ala-Gly- Val-Met-Thr-Ala- Ala Met-Ala-OCH3, (CH3)3-C-O-CO-Met-Lys-Ser-Leu-Leu-Ile-Leu-Val-Leu-Cys(benzyl)- Phe Leu-Pro- Leu-Ala-Ala-Leu-Gly-OH and (CH3)3-C-O-CO-Leu-Val-Leu-Gly-Ala-Val-Ile-Leu Gly- Thr-Thr-Leu-Leu- Ala-Gly-OCH3, corresponding to the signal sequences of lambda-receptor, lysozyme and the hydrophobic region of lipoprotein, respectively, show two negative bands at approx. 205 and 220 nm, characteristic of an alpha-helical conformation. Secondary structural features are discernible even in the shorter, 12-residue carboxy-terminal fragments of these signal peptides. A comparison of the conformation of the amino-terminal, central and carboxy-terminal fragments of lipoprotein signal sequence indicates that the central octapeptide fragment is more structurally ordered compared to the amino- and carboxy-terminal fragments. PMID- 2932159 TI - Carboxymethylated liver alcohol dehydrogenase: pH dependence of hydride transfer during ethanol oxidation. AB - The rate constant for the hydride transfer step during oxidation of ethanol by carboxymethylated alcohol dehydrogenase (alcohol: NAD+ oxidoreductase, EC 1.1.1.1) is dependent on a group with pKa 7.5. This pKa is higher than that for the native enzyme. A mechanism is proposed to account for the ionisation and the protein fluorescence change which occur during formation of the carboxymethylated enzyme-NAD+-ethanol complex. PMID- 2932160 TI - Effects of fructose 1,6-bisphosphate on the activation of yeast phosphofructokinase by fructose 2,6-bisphosphate and AMP. AB - Fructose 1,6-bisphosphate decreases the activation of yeast 6-phosphofructokinase (ATP:fructose 6-phosphate 1-phosphotransferase, EC 2.7.1.11) by fructose 2,6 bisphosphate, especially at cellular substrate concentrations. AMP activation of the enzyme is not influenced by fructose 1,6-bisphosphate. Inorganic phosphate increases the activation by fructose 2,6-bisphosphate and augments the deactivation of the fructose 2,6-bisphosphate activated enzyme by fructose 1,6 bisphosphate. Because various states of yeast glucose metabolism differ in the levels of the two fructose bisphosphates, the observed interactions might be of regulatory significance. PMID- 2932161 TI - An investigation of the SH1-SH2 and SH1-ATPase distances in myosin subfragment-1 by resonance energy transfer using nanosecond fluorimetry. AB - The separation between the two reactive thiols SH1 (Cys-704) and SH2 (Cys-694) and that between SH1 and the active site of myosin subfragment-1 were further investigated by Forster energy transfer techniques. The SH1-SH2 distance was determined with the probe 5-[[2-[(iodoacetyl)amino]ethyl] amino]naphthalene-1 sulfonic acid (AEDANS) attached to SH1 as the energy donor and 5 (iodoacetamido)fluorescein (IAF) attached to SH2 as energy acceptor. The results derived from measurements of donor lifetimes yielded a donor-acceptor separation in the range 26-52 A, with the distance R(2/3) based on rapid and isotropic probe motions being 40 A. These parameters were not sensitive to added MgADP, in agreement with previous results obtained by using the steady-state method. The SH1-SH2 distance was also determined with AEDANS attached to SH1 and N-(4 dimethylamino-3,5-dinitrophenyl)maleimide (DDPM) attached to SH2. The range in R for the AEDANS/DDPM pair was 12-36 A, with R(2/3) equal to 27 A. The transfer efficiency between these two probes increased by an average of 38% upon addition of MgADP. These results are in agreement with those previously reported (Dalbey, R.E., Weiel, J. and Yount, R.G. (1983) Biochemistry 22, 4696-4706), but the uncertainty in choosing an appropriate value of the orientation factor to describe the AEDANS-DDPM separation does not allow a unique interpretation of the observed increase in energy transfer because it could reflect either an increase in the average orientation factor or a decrease in the donor-acceptor separation. Nevertheless, the results are consistent with the notion that nucleotide binding induces structural perturbations that can be sensed by SH1 and SH2. The distance between SH1 and the ATPase site was determined with AEDANS linked to SH1 and the nucleotide analogue 2'(3')-O-(2,4,6-trinitrophenyl)adenosine 5'-diphosphate (TNP ADP) noncovalently bound to the active site as energy acceptor. The bound TNP-ADP was highly immobilized, with a depolarization factor approaching unity. The separation between AEDANS at SH1 and TNP-ADP at the active site was in the range 15-44 A. The actual minimal separation between SH1 and the active site is probably less than 15 A, which suggests that direct interaction between the two sites cannot be ruled out from energy transfer results. PMID- 2932162 TI - Influence of the regulatory light chain of fast skeletal muscle myosin on its interaction with actin in the presence and absence of ATP. AB - The effect of myosin LC2 modifications (phosphorylation or selective proteolytic removal of a seven-residue N-terminal peptide) and partial or complete removal of the whole LC2 was studied under various conditions. (1) Actin binding in the absence of ATP is not influenced by the nature of the myosin species (phosphorylated, dephosphorylated or devoid of LC2). (2) A 50% inhibition of K+/EDTA-ATPase was obtained with actin concentrations hardly different when phosphorylated and dephosphorylated myosins were compared (of the order of 5 microM), whereas both myosin devoid of LC2 and myosin in which the LC2 N-terminal peptide has been removed required significantly higher concentrations of actin (13.0 +/- 2 and 12.0 +/- 2.0 microM, respectively). (3) Dissociation of the actomyosin complex at high ionic strength with nucleotides is not influenced by phosphorylation. (4) Actin activation of Mg2+-ATPase is enhanced when LC2 is phosphorylated; no activation enhancement is observed with myosin devoid of LC2. (5) Translational diffusion coefficient measurements of myosin in high-ionic strength solutions indicate a tendency for LC2-deprived myosin to form autoassociation oligomers. It thus appears that a structural modification (partial cleavage or removal of LC2) induces important structural changes in myosin, pointing to a role for LC2 in the intrinsic conformation of the molecule and its interaction potentialities. Effects of LC2 removal at high ionic strength are best explained by interactions bearing no relationship to physiological functions. A physiologically significant effect of LC2 phosphorylation requires a minimum degree of organization (actomyosin complex) to be expressed in which LC2 could play the role of a return-spring in the cross-bridge mechanism. PMID- 2932163 TI - Reduction of 3-keto-5 beta-cholanoic acid to lithocholic and isolithocholic acids by human liver cytosol in vitro. AB - The formation of lithocholic and isolithocholic acids from 3-keto-5 beta cholanoic acid by human liver cytosol was examined in vitro. Liver cytosol was incubated at various pH levels with 3-keto-5 beta-cholanoic acid in a phosphate buffer containing NADPH or NADH; the products formed were analyzed by gas chromatography. Results showed that human liver cytosol reduced 3-keto-5 beta cholanoic acid to lithocholic acid at a pH level of 7.0 or above and to isolithocholic acid at a pH level of 6.0 or below when NADPH was used as a coenzyme, and it was reduced to isolithocholic acid only when NADH was used. Furthermore, two peaks for the reducing enzymes could be clearly found by column chromatography of Affi-Gel Blue. These results indicate that human liver cytosol contains two enzymes acting on reduction of 3-keto-5 beta-cholanoic acid to lithocholic and isolithocholic acids, which are dependent on the pH level and the use of NADPH or NADH in vitro. Since the 3 beta-dehydrogenation was inhibited by the addition of pyrazole, an alcohol dehydrogenase inhibitor or ethanol, and the major peak of 3 beta-hydroxysteroid dehydrogenase coincided with the peak of alcohol dehydrogenase on Affi-Gel Blue chromatography, at least some of the cytosolic 3 beta-hydroxysteroid dehydrogenase seemed to be identical to or to have characteristics similar to alcohol dehydrogenase. PMID- 2932164 TI - Endogenous factors that modulate yeast glucan synthetase in cell-free extracts. AB - Yeast 1,3-beta-D-glucan synthetase (EC 2.4.1.34) activity is modulated by endogenous factors obtained by the extraction of different subcellular fractions with hot water. Cell wall fractions were enriched in activators while supernatant fractions also contained appreciable amounts of inhibitors. The action of these compounds requires the presence of EDTA. Maximal activation by the stimulatory material was reached when assayed in sonicated enzymatic preparations that had been obtained by mechanical breakage of cells in water. The activating material derived from cell wall fractions contained a mixture of low molecular weight compounds. They were found to be different from GTP as deduced from their resistance to alkaline phosphatase and different elution profile in gel filtration. The supernatant material was also heterogeneous with regard to both activators and inhibitors. The combined effect of GTP and activating material derived from cell wall fractions was supraadditive. The polymers synthesized in the absence and in the presence of the endogenous activator were characterized as beta-1,3-glucans on the base of their resistance to periodate and susceptibility to beta-glucanases. However, the length of the radioactive chains was greater when synthesized in the presence of the activator. This was mediated by an increase in the Vmax of the synthetase. PMID- 2932165 TI - [Electron microscopy study of the interaction of F-protein (phosphofructokinase) with actin-containing filaments]. AB - By the use of electron microscopy and optical diffraction the interaction of F protein (phosphofructokinase) with F-actin and reconstructed thin filaments has been revealed. F-protein distributes itself along the filament bundles at regular intervals of 36-38 nm. PMID- 2932166 TI - Evidence for a 2-oxoglutarate dehydrogenase complex activity in mitochondria of Neurospora crassa and compared localization with the pyruvate dehydrogenase complex. AB - A 2-oxoglutarate dehydrogenase complex activity is demonstrated in Neurospora crassa mitochondria. A submitochondrial fractionation by digitonin treatment followed by freeze-thawing enables measurement of a well preserved activity in the mitochondrial matrix. In contrast to other reports, the pyruvate dehydrogenase activity is also found to be localized in the matrix. PMID- 2932167 TI - [Dialdehyde derivatives of purine mononucleotides: substrate properties and affinity modification of myosin ATPase]. AB - It was demonstrated that the dialdehyde derivative of ATP is a good substrate for Ca-ATPase of heavy meromyosin (Km = (1.2-1.4) X 10(-4) M; V = VATP). At the same time, this compound can induce irreversible inhibition of the enzyme. Since oxo ATP is rapidly hydrolyzed by myosin to form oxo-ADP, this inhibition is the result of the enzyme interaction with oxo-ADP. It was found that the kinetics of heavy meromyosin inhibition by oxo-ADP are typical of affinity modification; in this case ATP fully protects heavy meromyosin from the activity loss. Similar results on the irreversible inhibition of the ATPase activity under the action of oxo-ADP were obtained in the presence of myosin, heavy meromyosin, subfragment I and natural actomyosin and in the absence of bivalent cations, thus suggesting the modification of the active center of myosin ATPase. PMID- 2932168 TI - [Use of the desirability function method for assessing water quality by periphyton composition]. AB - Water quality generalized index according to periphyton community obtained by the method of desirability function has been used to estimate the Moscow River pollution. To reveal the indicator species by this method one-year observation period is required. The indicator species list presented here can be recommended for the calculation of generalized index according to the periphyton data for the Moscow River. PMID- 2932169 TI - Active immunization of gilts against gonadotropin-releasing hormone: effects on secretion of gonadotropins, reproductive function, and responses to agonists of gonadotropin-releasing hormone. AB - Sexually mature gilts were actively immunized against gonadotropin-releasing hormone (GnRH) by conjugating GnRH to bovine serum albumin, emulsifying the conjugate in Freund's adjuvant, and giving the emulsion as a primary immunization at Week 0 and as booster immunizations at Weeks 10 and 14. Antibody titers were evident by 2 wk after primary immunization and increased markedly in response to booster immunizations. Active immunization against GnRH caused gonadotropins to decline to nondetectable levels, gonadal steroids to decline to basal levels, and the gilts to become acyclic. Prolactin concentrations in peripheral circulation were unaffected by immunization against GnRH. The endocrine status of the hypothalamic-pituitary-ovarian axis was examined by giving GnRH and two agonists to GnRH and by ovariectomy. An i.v. injection of 100 micrograms GnRH caused release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in control animals, but not in gilts immunized against GnRH. In contrast, administration of 5 micrograms D-(Ala6, des-Gly-NH2(10] ethylamide or 5 micrograms D-(Ser-t-But6, des-Gly-NH2(10] ethylamide resulted in immediate release of LH and FSH in both control and GnRH-immunized gilts. Circulating concentrations of LH and FSH increased after ovariectomy in the controls, but remained at nondetectable levels in gilts immunized against GnRH. Prolactin concentrations did not change in response to ovariectomy. We conclude that cyclic gilts can be actively immunized against GnRH and that this causes cessation of estrous cycles and inhibits secretion of LH, FSH, and gonadal steroids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2932172 TI - Proceedings of the Fifth International Symposium on Mass Spectrometry in Life Sciences. Ghent, Belgium, 15-18 May 1984. PMID- 2932171 TI - Density and disposition of Ca2+-ATPase in sarcoplasmic reticulum membrane as determined by shadowing techniques. AB - We have studied the disposition of calcium ATPase in the native sarcoplasmic reticulum (SR) membrane of vertebrate muscles by rotary shadowing of freeze-dried isolated vesicles and of freeze-fractured in situ membranes. The predominant disposition of the ATPase molecules is disorderly, but small oligomers (dimers, tetramers, and occasionally larger aggregates) are seen. In vesicles from white hind legs of rabbits, the density of ATPase over nonjunctional SR is 31 34,000/microns2. ATPase density is always quite high, but small protein-free lipid patches may be interspersed with it. PMID- 2932170 TI - Ordered arrays of Ca2+-ATPase on the cytoplasmic surface of isolated sarcoplasmic reticulum. AB - Isolated sarcoplasmic reticulum (SR) vesicles with polymerized calcium pump protein were freeze-dried and rotary shadowed following uranyl acetate stabilization. This technique allows direct observation of a single side of the vesicle without requiring optical filtering. The heads of individual ATPase molecules, projecting above the cytoplasmic surface, are clearly resolved in the replicas. Ca ATPase molecules form extensive arrays in vanadate-treated, rabbit SR vesicles and in gently isolated, native SR vesicles from scallop. Gentle isolation results in limited areas of orderly structure in native SR isolated from vertebrate muscles. Special attention is given to the effect of various shadow thicknesses on the appearance of the heads. This information is essential to the interpretation of images in the accompanying paper (Franzini-Armstrong, C., and D.J. Ferguson, 1985, Biophys. J., 48:607-615). PMID- 2932173 TI - Laser microprobe mass analysis: a review of applications in the life sciences. AB - The characteristics and analytical utility of laser microprobe mass analysis (LAMMA) are described and evaluated, and a short history of this recent microanalytical technique is presented. A review of the areas of application of LAMMA and related laser microprobes is presented with special emphasis on applications in the life sciences. PMID- 2932174 TI - Selected ion monitoring analysis of pseudoracemic hexobarbital and its major metabolites in blood and urine of rats. AB - A stereospecific synthesis of N1-(2H3)-labelled R(-)-hexobarbital is described. A sensitive and rapid selected ion monitoring assay procedure for pseudoracemic hexobarbital, consisting of equal amounts of S(+)-hexobarbital (1a) and (2H3)-R( )-hexobarbital (1b) in 100 microliters blood samples of rats was developed. Both the parent enantiomers in blood and three major metabolites excreted in urine were quantified. An application of the method in rats is described, and the results are compared to previously obtained data of separately administered enantiomers. PMID- 2932175 TI - Trace determination and isotopic analysis of the elements in life sciences by mass spectrometry. AB - The main ionization methods in a mass spectrometer for isotope ratio determinations of the elements are discussed in this review. These methods are thermal ionization, spark source, electron impact, inductively coupled plasma and field desorption. As concerns thermal ionization, electron impact and field desorption, a survey of the possibilities of isotope analyses in the periodic table of the elements is given. Besides kinetic studies, trace element determination by isotope dilution technique is the main application for isotope ratio measurements of the elements. The definitive method, isotope dilution mass spectrometry, is discussed as a potential tool for achieving accurate and precise trace analyses. Using field desorption mass spectrometry, one example of calcium kinetics in man and one example of thallium trace determination in an animal tissue are given. Other metal trace analyses with the isotope dilution technique are presented for biological and medical samples using positive thermal ionization mass spectrometry. Negative thermal ions are formed for the mass spectrometric analysis of non-metals and non-metal compounds in food samples, e.g. for iodine and nitrate in milk powder. Preliminary results with the isotope dilution technique are presented for a new quadrupole thermal ionization mass spectrometer which is a low-cost instrument and can be easily handled. PMID- 2932176 TI - The metabolism of tromantadine. AB - The metabolism of the antiviral drug tromantadine (1-adamantyl-2-(2 dimethylaminoethoxy)acetamide) was studied after an oral dose of 120 mg tromantadine hydrochloride using capillary gas chromatography/mass spectrometry. Most of the dose was excreted unchanged with the urine. Six metabolites could be identified. The main metabolic products were 1-aminoadamantane (amantadine) and 1 adamantyl-(2-hydroxy)acetamide. Further metabolic pathways were demethylation of the dimethylamino function and oxidative desamination to an unstable aldehyde which is oxidized to a carbonic acid or reduced to an alcohol. PMID- 2932177 TI - Rapid, sensitive and specific determination of oxytetracycline residues in bovine milk and meat by CAD MIKEs analysis at the 1 ppb level. AB - A rapid and sensitive method for the selective detection and quantification of oxytetracycline residues at the ppb level in crude extracts of bovine milk and meat is described. The technique employed is a tandem mass spectrometric method: CAD MIKE spectrometry (collisionally activated decomposition mass-analysed ion kinetic energy spectrometry). Quantification is performed by single ion monitoring of CAD species of oxytetracycline and of its internal standard. PMID- 2932178 TI - A revision of the metabolic disposition of amantadine. AB - Amantadine is one of the most commonly used drugs for the control of tremor in Parkinson's disease. Additionally, it has an antiviral action in the prevention of type A influenza. It has been previously reported that amantadine is nearly completely eliminated in the urine. No metabolites have been detected. Surprisingly, in a case of amantadine overdose, several metabolites could be identified by gas chromatography/mas spectrometry. This finding prompted us to re investigate the metabolism of amantadine under a therapeutic dosing regimen. The bulk of the dose was eliminated unchanged. However, eight metabolites could be identified. Besides N-acetylation which is the major metabolic pathway, several rather unusual metabolic pathways were observed: N-methylation, formation of Schiff bases and N-formiates. No metabolites with a hydroxylated adamantane ring system could be detected. PMID- 2932179 TI - Evaluation of isotope ratio (IR) mass spectrometry for the study of drug metabolism. AB - Isotope ratio (IR) mass spectrometry was evaluated for the study of drug metabolism and balance using 13C, 15N2-labelled antipyrine (AP) as a test drug. Rats were given 40 mg kg-1 (13C,15N2)AP intraperitoneally. Breath, urine, faeces and blood were collected. Except for breath, samples were combusted in sealed quartz tubes. The resulting CO2 and N2 were analysed for excess 13C and 15N, relative to pre-dose samples, by IR mass spectrometry. In addition, blood levels of AP and cumulative excretion of urinary AP metabolites were determined by gas chromatography/mass spectrometry/selected ion monitoring (GC/MS/SIM) and high performance liquid chromatography (HPLC) respectively. Excess 13C and 15N levels in blood were comparable with observed levels of AP, and urinary recoveries of 13C (42%) were in good agreement with those calculated from HPLC data (45%). N Demethylation, one of the important pathways of AP metabolism, was most rapidly determined by excess 13CO2 excretion in breath (8%). The IR mass spectral analysis complemented gas chromatographic/mass spectrum and HPLC analyses, and was less complex. PMID- 2932180 TI - Keto acids in tissues and biological fluids: O-t-butyldimethylsilyl quinoxalinols as derivatives for sensitive gas chromatographic/mass spectrometric determination. AB - Quinoxalinol t-butyldimethylsilyl ethers were prepared from three branched-chain and from two aliphatic unbranched 2-keto acids. The electron impact (EI) mass spectra display pronounced [M-57]+ ions. With 39-51% of total ion current contained within them, sensitivity is greater than on chemical ionization (CI) mass spectrometry of O-trimethylsilyl derivatives. Mass spectra and chromatographic behaviour of these novel keto acid derivatives are discussed and preliminary quantitative data from rat muscle are given. PMID- 2932181 TI - A rapid analytical technique for the determination of energy expenditure by the doubly labelled water method. AB - The doubly labelled water method involves the administration of water enriched in 2H and 18O followed by determination of the turnover rates of these isotopes. Since 18O is eliminated from the body as both CO2 and water, while 2H leaves only as water, the difference between the two turnover rates provides a measure of CO2 production and hence energy expenditure. Isotopic analysis by conventional stable isotope ratio analysis (SIRA) is labour intensive and time consuming, as it requires off-line conversion of water samples to gases (H2 and CO2) followed by sequential analysis for each of the two isotopes using the mass spectrometer. Lack of suitable automated instrumentation with the ability to process large numbers of samples has prevented routine application of the method. We describe here an automated technique in which body water samples (urine, saliva, breath water or milk) are analysed simultaneously for 2H and 18O. The single bench system comprises two mass spectrometer analysers, one for measuring 2H from H2 gas, the other for measuring 18O from the water vapour (masses 18, 20). Both analysers share a common heated inlet system into which microlitre quantities of the body fluids are injected from an autosampler (102 samples). The water vapour flows both directly to one analyser for 18O measurement and into a uranium reduction furnace for conversion to H2, prior to 2H measurement by the second analyser. Both analysers also share vacuum and electronic components, enabling savings in both space and cost. In this paper we present results illustrating performance characteristics and procedures for routine application to human subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2932182 TI - Combined thin layer chromatography/mass spectrometry: an application of 252Cf plasma desorption mass spectrometry for drug monitoring. AB - The pharmacokinetic analysis is performed in a three-step procedure: sample extraction, sample purification by thin layer chromatography (TLC) and quantitative sample detection by time-of-flight (TOF) mass spectrometry. 252Cf plasma desorption (PD) mass spectrometry utilizing the fission fragment-induced ionization and desorption of non-volatile compounds is suitable as a universal, non-destructive detector in TLC. Here TLC and mass spectrometry are operated in an off-line combination. As an example some pharmacokinetic data for etoposide (VP 16-213) together with calibration data are presented. The new experimental method is discussed in terms of sensitivity and detection limit. PMID- 2932183 TI - Identification and quantification of metabolite conjugates of activated cyclophosphamide and ifosfamide with mesna in urine by ion-pair extraction and fast atom bombardment mass spectrometry. AB - The high bladder toxicity of the alkylating oxazaphosphorine anticancer drugs, cyclophosphamide and ifosfamide is effectively reduced by the concomitant administration of mesna (sodium 2-mercaptoethane sulphonate). The formation and rapid urinary excretion of conjugates of the activated (4-hydroxylated) oxazaphosphorine metabolites with mesna has been suggested as the pharmacological basis for the selective detoxification, but separation and identification of such metabolites in vivo have been extremely difficult due to their high polarity and chemical lability. In this study an ion-pair extraction procedure in combination with positive and negative ion fast atom bombardment mass spectrometry has been developed which enabled the identification and quantification of the conjugation products of activated oxazaphosphorine metabolites with mesna in urine. The conjugates extracted as the tetra-n-butylammonium salts are directly identified by their characteristic positive molecular ion adducts and fragment ions, and the corresponding abundant molecular anions. The pattern of molecular and fragment ion formation was established by comparison of the fast atom bombardment mass spectra of synthetic cyclophosphamide-mesna conjugates with various organic and inorganic counter ions. The ifosfamide-4-(2-thioethylsulphonate) (ifosfamide mesna) conjugate was identified as a metabolite in the urine of rats, and in patients after administration of the combination, ifosfamide + mesna. By means of a two-step extraction and with the use of suitable analogues as internal standards, procedures for the quantification of parent oxazaphosphorine and of oxazaphosphorine-mesna conjugates by negative ion fast atom bombardment mass spectrometry have been developed, and first examples for the determination of excretion kinetics are described. PMID- 2932184 TI - Measurement of thromboxane B2 in human urine by isotope dilution and negative ion chemical ionization mass spectrometry. AB - A highly sensitive and specific assay for the quantification of thromboxane B2 (TXB2)(1) in human urine is described. The method is based on the use of low blank (1H less than or equal to 0.2%) tetradeuterated internal standard 2 (18, 18, 19, 19-2H4-thromboxane B2), whose chemical synthesis is reported. After purification and high-performance liquid chromatography (HPLC) samples are derivatized to give an open-chain derivative of thromboxane B2, the methoxime pentafluorobenzyl ester tris(trimethylsilyl) ether (TXB2-MO-PFB-TMS3), most suitable for negative ion chemical ionization mass spectrometry. In the selected ion monitoring mode limits of detection per injection for pure standards and biological samples of 10 pg and 30 pg, respectively, are established. Normal urinary excretion of 1 in humans is 37-112 ng/24 h (n = 12). PMID- 2932185 TI - Measurement of isotope ratios in organic compounds at picomole quantities by capillary gas chromatography/quadrupole electron impact mass spectrometry. AB - Measurements of isotope ratios in organic compounds at nanomolar concentrations in biological fluids require sensitive and selective gas chromatographic/mass spectrometric methods. The efficiency of sample preparation procedures must be high and gas chromatographic conditions must assure high resolution chromatography producing narrow, intense peaks. Mass spectrometric conditions must create suitable mass fragments, preferably in the high mass range. Detection, controlled by selected ion monitoring (SIM), requires the use of small mass intervals and adequate acquisition times. However, the choice of optimal conditions is limited by the need to acquire multiple data points for the eluting compound. The effects of these variables on the precision of isotope ratio measurements have been investigated to develop an optimal method for isotope ratio measurements in serum bile acids at low concentrations (0.05-8 micromol l 1). With a 25 m X 0.32 mm fused silica capillary OV-1701 column and cold on column injection, peak widths of 10 s were obtained. Quadrupole mass spectrometry in the electron impact ionization mode (70 eV) and selected ion monitoring (SIM)(mass interval 1/16 u, acquisition time 100 ms) allowed precise (cv less than 1.5%) isotope ratio measurements for chenodeoxycholic, cholic and deoxycholic acid in a single run at quantities as low as 5 pmol injected on the column. SIM switching during the run permitted isotope ratio measurements (cv less than 2.2%) for an additional six bile acids, normally detected in the serum of healthy subjects. PMID- 2932186 TI - Liquid chromatography/mass spectrometry of fatty acids as their anthrylmethyl esters. AB - The mass spectra of a series of saturated and unsaturated fatty acids have been recorded as their anthrylmethyl esters using a liquid chromatographic mass spectrometric interface. The spectra show an intense peak for the aromatic nucleus, and a molecular ion. The liquid chromatographic/mass spectrometric separation was performed on a reverse phase column using a solvent system of acetone + acetonitrile. While a complete separation of the fatty acids known to occur in man was not achieved, the recognition of all of these acids is possible using a scanning mode or by ion monitoring. PMID- 2932187 TI - Hydroxyl negative chemical ionization mass spectrometry linked with collisionally activated decomposition. A modern analytical tool in inborn errors of metabolism. AB - Two kinds of inborn errors of metabolism, dicarboxylic aciduria and hyperoxaluria, have been studied by means of hydroxyl negative ion chemical ionization [NICI(OH-)], linked with collisionally activated decomposition experiments on the [M-H]- species of the pathognomonic organic acids. This method has led to non-controversial qualitative determinations of C4-C10 dicarboxylic acids and oxalic, glyceric and glyoxylic acids. NICI(OH-) linked with collisionally activated decomposition mass analysed ion kinetic energy spectrometry (CAD MIKES) is proposed herein for diagnostic purposes, as a valid mass spectrometric alternative to standard gas chromatographic/mass spectrometric analysis. The procedure is characterized by simplified sample treatment and by fast execution. PMID- 2932188 TI - [Effect of taurine on Ca, Mg-ATPase activity in human platelets and on their aggregation]. AB - Effect of taurine (25 mM) on calcium metabolism in human platelets was studied. Ca, Mg-ATPase activity is significantly increased upon addition of 25 mM of taurine to the incubation medium. The activation is absent or reduced in the presence of trifluoroperazine and beta-alanine and after preincubation of platelets with colchicine and verapamil. The rate of ADP (3.5 X 10(-6) M)-induced platelet aggregation is reduced by half upon taurine addition to platelet-rich plasma. The possible role of taurine in intracellular calcium translocation and the following alteration of platelet activity is suggested. PMID- 2932189 TI - [Interaction of smooth muscle plasma membranes with flat lipid membranes]. AB - The method of implantation of smooth muscle cells from plasma membranes (PM) of the rabbit intestine into flat lipid membranes (FLM) is described. The method is based on the pretreatment of PM vesicles with asolectin liposomes in the ratio that provides the activation of membrane ATPases. Thus modified FLM possesses channel conductivity. PMID- 2932190 TI - Toxicity of lead to soil respiration: mediation by clay minerals, humic acids, and compost. PMID- 2932191 TI - Life-events and psychological disturbance in chronic low back pain. AB - Stressful life-events have been identified as contributing to psychological disturbance in chronic low back pain (CLBP). However, previous research has focused on the presence versus absence of generalized distress and failed to distinguish between positive and negative events. The present study examined the relationship of positive and negative life-events to various aspects of distress as measured by the eight clinical scales of the MMPI. Negative life-events were found to be associated primarily with depression and social maladjustment, while positive events were inversely related to somatic concern. PMID- 2932192 TI - Use of a combined groin-tensor fasciae latae flap for reconstruction of a full thickness defect of the abdominal wall. AB - Two cases are presented in whom full-thickness defects of the abdominal wall were repaired by combined groin-tensor fasciae latae flaps nourished only by the superficial circumflex iliac artery. The dissection of the flap is simple and it will probably cover even the upper parts of the flank. PMID- 2932193 TI - Cardioprotection by the calcium antagonist PN 200-110 in the absence and presence of cardiodepression. AB - The globally-ischaemic Langendorff rabbit heart model has been used to study the cardioprotective effects of the dihydropyridine PN 200-110 (PN) at two doses, one having no negative inotropic effect and a higher dose causing a 62 +/- 5% reduction in contractility. Following 45 min no-flow global ischaemia, recovery was monitored for a period of 90 min reperfusion. Hearts were paced at a constant rate throughout experiments. Contractile force and coronary flow were recorded continuously. Tracer microspheres were injected at regular intervals to assess regional flow distributions, drill biopsies were taken to determine tissue high energy phosphate content, and enzyme leakage in the coronary effluent measured during the first 15 min of reperfusion. Untreated hearts recovered 21 +/- 2% of their initial contractile force and flow to all heart regions was reduced. In particular, endocardial flow fell to 20% of its pre-ischaemic level, with the ratio of flow to the endocardium (endo)/epicardium (epi) decreasing from ca. 1.0 to 0.4. Hearts treated with 2 X 10(-8)M PN (included in the perfusate from 30 min before ischaemia until 30 min after ischaemia) recovered 49 +/- 2% of their initial, pretreatment contractile force, and following the ischaemia the endo/epi ratio was not significantly changed from the pre-ischaemic value. The lower PN dose (3 X 10(-10)M) afforded a lesser degree of protection, contractility recovering to 29 +/- 4% of the initial level, with an endo/epi ratio of 0.7 after 90 min reperfusion. 6 The two PN doses afforded a similar degree ofprotection against enzyme leakage which was in both cases significantly less than in untreated hearts. 7 Myocardial ATP and creatine phosphate content was markedly reduced by the ischaemic episode. Neither PN dose modified this depletion. 8 These results suggest that whilst cardiodepression may well offer protection against ischaemic damage, this is not the sole mechanism wherby PN (and possibly other calcium antagonists) can protect the heart. Preservation of blood flow to the inner layers of the left ventricular wall is likely to be one of the major factors underlying the enhanced recovery shown by PN. PMID- 2932194 TI - Atrial natriuretic factor causes specific relaxation of rat renal arcuate arteries. AB - We have investigated the effect of a synthetic 'atrial natriuretic factor' (ANF) on induced tone in rat isolated renal arcuate arteries (lumen diameter ca. 250 microns), and compared this with the effects of synthetic ANF on resistance vessels of similar size taken from the mesenteric, femoral, cerebral and coronary vasculature. Synthetic ANF was found to cause relaxation of the renal vessels when these were sub-maximally activated with K+, noradrenaline or 5 hydroxytryptamine, but had no effect on the responses of the other vessels to these agonists. Synthetic ANF had a near maximal effect (65% relaxation) at 100 nM, with an IC50 of 7.9 nM. The relaxant effect of synthetic ANF on the renal vessels was fully maintained for at least 15 min. Hydralazine (100 microM) caused relaxation of renal vessels (47%) and coronary vessels (42%), but had no effect on the other vessel types. By contrast, sodium nitroprusside (1 microM) relaxed all vessel types. The relaxant action of synthetic ANF on the renal vessels was seen in the presence of ouabain (1 mM), propranolol (1 microM), phentolamine (1 microM), atropine (1 microM) and felodipine (1 nM). In t renal vessels, synthetic ANF had no effect on membrane potential, measured with intracellular electrodes, despite the simultaneously measured relaxation. Synthetic ANF had no effect on the efflux of 22Na+ in either renal or mesenteric vessels. The results demonstrate that synthetic ANF has a specific and prolonged relaxant effect on renal small arteries, and are consistent with this effect being mediated through specific receptors. PMID- 2932196 TI - Excitatory neuronal responses to dopamine in the cerebral cortex: involvement of D2 but not D1 dopamine receptors. AB - The technique of microelectrophoresis was used to evaluate the relative contribution of D1 and D2 dopamine receptors towards the mediation of the excitatory response of single neurones to dopamine in the somatosensory cortex of the rat. The selective D1 dopamine receptor agonist, SKF 38393, failed to excite any of the cells to which it was applied. In contrast, the selective D2 dopamine receptor agonist, LY 171555, excited the majority of cells tested. The apparent potency of LY 171555 was significantly lower than that of dopamine. When the mobilities of SKF 38393 and LY 171555 were assessed by an in vitro method, they were found to be at least as great as those of dopamine and phenylephrine, suggesting that the lack of effect of SKF 38393 and the lower apparent potency of LY 171555 compared to dopamine reflect genuine biological phenomena. The alpha 1 adrenoceptor antagonist, prazosin, discriminated between excitatory responses to the alpha 1-adrenoceptor agonist, phenylephrine, and LY 171555: responses to phenylephrine were more susceptible to antagonism than were those to LY 171555. The dopamine receptor antagonist, haloperidol, produced the reverse discrimination: responses to LY 171555 were more affected than were those to phenylephrine. Neither antagonist reduced the response to the control agonist, acetylcholine. When applied continuously with low ejecting currents, LY 171555 antagonized the excitatory response to dopamine while the response to phenylephrine was relatively preserved. The response to acetylcholine was unaffected. When similarly applied, SKF 38393 had no selective action on the response to dopamine. 6 These results suggest that D2 dopamine receptors are involved in mediating the excitatory neuronal response to dopamine in the cerebral cortex, whereas DI dopamine receptors are unlikely to be involved. LY 171555 appears to act as a partial agonist at D2 dopamine receptors in this test system. PMID- 2932195 TI - A study of the histamine H2-receptor mediating relaxation of the parenchymal lung strip preparation of the guinea-pig. AB - The relaxation produced by several H2-receptor agonists and forskolin was investigated on strips of guinea-pig lung parenchyma. Dimparit, 1 microM to 10 mM, 4-methyl histamine, 0.5 microM to 100 microM and impromidine, 10 nM to 1 microM, had no effect on the tone of the unstimulated strips of lung parenchyma but caused a dose-dependent relaxation of strips that were contracted by 2 pyridylethylamine (2-PEA), 15 microM. Forskolin, 10 nM to 4 microM, produced a dose-dependent relaxation of both the stimulated and unstimulated lung strips. The muscarinic antagonist atropine, 1 microM, and the beta 2-adrenoceptor antagonist propranolol, 10 microM, had no effect on the dose-response curve for dimaprit-induced relaxation of the lung strip. The dose-response curve for dimaprit was shifted to the right in a dose-dependent manner by increasing concentrations of a variety of H2-antagonists. Schild plots produced a straight line for all the H2-antagonists with slopes not significantly different from unity. The equilibrium dissociation constants for the H2-antagonists on the lung strip preparation were similar to those previously reported for inhibition of the chronotropic activity of histamine on guinea-pig right atria and inhibition of [3H]-tiotidine binding to homogenates of guinea-pig lung parenchyma. PMID- 2932197 TI - CGS 12970: a novel, long acting thromboxane synthetase inhibitor. AB - CGS 12970 is a potent selective inhibitor of human platelet thromboxane synthetase in vitro (IC50 = 12 nM). It is four orders of magnitude less potent as an inhibitor of sheep seminal vesicle cyclooxygenase, bovine aorta prostacyclin synthetase and human leucocyte 15-lipoxygenase. The compound inhibited collagen induced thromboxane B2 production by human platelets in vitro without an effect on the accompanying platelet aggregation induced by collagen, ADP, platelet activating factor, thrombin, arachidonic acid or the prostaglandin mimetic, U 46619. Administration of CGS 12970 to rats inhibited collagen-induced thromboxane B2 production but had no effect on platelet aggregation ex vivo. It also had no effect on platelet aggregation induced by thrombin or on plasma clotting times. A single oral dose of 1 or 3 mg kg-1 to rabbits inhibited thromboxane B2 production in clotting blood ex vivo for 12 or 24 h respectively. CGS 12970 inhibited thromboxane B2 production in vivo induced by intravenous administration of collagen to rats or calcium ionophore to guinea-pigs. In both cases there was a concomitant elevation of immunoreactive 6-keto-prostaglandin F1 alpha but no effect on the induced thrombocytopenia. As with other thromboxane synthetase inhibitors, CGS 12970 prolonged tail bleeding time in the rat. However, CGS 12970 was not as potent as other thromboxane synthetase inhibitors in this test. In addition to these usual effects of thromboxane synthetase inhibitors, CGS 12970 inhibited the thrombocytopenia induced by the Forssman reaction or ADP administration. In these tests the effect of the compound was of short duration. 8 CGS 12970 had no effect on the thrombocytopenia associated with the Arthus reaction which distinguishes it from cyclo-oxygenase inhibitors. It also had no effect on thrombus formation on a cotton thread in an arteriovenous shunt in the rat. PMID- 2932198 TI - Studies on the site and mechanism of the inhibitory action of intracerebral histamine on the cold-stimulated thyrotropin secretion in male rats. AB - The locus of the inhibitory action of histamine on cold-stimulated TSH secretion was studied in male rats. Various histaminergic drugs were given either into the median eminence (ME), the third ventricle, the rostral and caudal part of anterior hypothalamus (rAH and cAH) or the posterior hypothalamus (PH) of conscious rats. When infused into ME, histamine (5 and 10 micrograms/rat) decreased and mepyramine (2.5 micrograms) increased the cold-stimulated TSH secretion while a larger dose of mepyramine (10 micrograms/rat), impromidine (0.05 and 0.1 microgram/rat), 2-pyridylethylamine (2-PEA; 5 and 10 micrograms/rat) and cimetidine (2.5 and 7.5 micrograms/rat) had no effect. The inhibitory action of histamine (5 micrograms/rat) was most marked 30 min after the infusion into ME and it remained significant for at least 50 min. Neither cimetidine (50 and 100 mg/kg i.p.) nor mepyramine (10 and 20 mg/kg i.p.) antagonized the inhibitory action of histamine (5 micrograms/rat) in ME. Histamine (10 micrograms/side) inhibited the cold-stimulated TSH secretion likewise when infused bilaterally either into rAH, cAH or PH. TSH secretion induced by exogenous TRH (100 ng i.p.) was also inhibited by histamine (1 microgram/rat) given into the third ventricle. In conclusion, histamine seems to have an inhibitory action on the cold-stimulated TSH secretion. This action is apparently mediated through areas close to the third ventricle. The mechanism of this action seems to be fairly non-specific, i.e. it is mediated through neither H1- nor H2-receptors. PMID- 2932200 TI - Aqueduct stenosis induced by a single injection of antivitamin. AB - Hydrocephalus with aqueduct stenosis was a consistent feature in mice which received a single intraperitoneal injection of 6-aminonicotinamide (6-AN) on day 5 postnatal. Chronological investigation revealed that 6-AN-treated mice had aqueductal obstruction with edematously swollen ependymal cells and spongy changes in the periaqueductal gray matter in the early stage (on days 5 and 7 postinjection). However, these cytoplasmic edema of the ependymal and glial cells totally subsided by day 30 postinjection, leaving an obliterated aqueduct with a few remnants of ependymal cells without reactive gliosis. This abnormality of aqueductal lesions in the chronic stage was similar to those of human congenital hydrocephalus. These findings raise the possibility that some form of human congenital hydrocephalus may result from ependymal cell degeneration due to exposure to certain noxious substances in the perinatal period. PMID- 2932199 TI - Enhanced survival of apparent presynaptic elements on polylysine-coated beads by inhibition of non-neuronal cell proliferation. AB - Increased survival of presynaptic-like neuronal profiles was found in cell cultures of rat cerebellum when the non-neuronal cell numbers were reduced with an antimitotic drug. In both treated and untreated cell cultures, neurites grew onto the polylysine-coated surface of sepharose beads and formed a swelling. The neuronal swelling contained an accumulation of synaptic vesicles and a membrane density at the site of contact with the bead and was called an apparent presynaptic element. The apparent presynaptic elements in untreated cultures increased in number from the time the beads were added to the culture to 7 days incubation and then showed a decrease to one half the 7-day value at 14 days incubation. A 75% reduction in cell division of non-neuronal cells was seen in cultures exposed to a 5 X 10(-6)M cytosine arabinoside (Ara-C) for 2 days. Adding polylysine-coated beads to cultures treated with Ara-C showed at 14 days incubation a 7-fold increase in the number of apparent presynaptic elements as compared to untreated cultures. Additional experiments examined the numbers of neurites on the beads and found only small differences between treated and untreated cultures. A decrease, however, was shown in the number of glial fibrillary acidic protein staining astrocytes on the surface of the beads in treated cultures. The reduction of astrocytes by Ara-C appeared to enhance the survival of apparent presynaptic elements but did not enhance the growth of neurites. These results suggest that proliferating non-neuronal cells at a site of injury in the central nervous system may inhibit the formation of synaptic contacts and the growth of neurites through the site of injury. PMID- 2932201 TI - The role of endogenous serotonin in phasic LH release. AB - Injection of the serotonin inhibitor, fluoxetine (75 micrograms) into the hypothalamus (IC) of ovariectomized (Ovx.) rats treated with 17beta-Estradiol (E2) and parachlorophenylalanine (PCPA 150 mg/kg) significantly increased the luteinizing hormone (LH) in these rats 24 hours later when PCPA had suppressed the LH surge in a parallel group of sham rats. There was a temporal delay in these changes of LH (and by implication serotonin metabolism), since there was no significant effect on the blocked LH surge within two hours of the injection. Since steroids play a major role in gonadotropin secretion and PCPA has been shown to depress LH release, it is interesting that E2 increased the rate of H-3 serotonin (1 X 10(-7) M) uptake in hypothalamic synaptosomes. This suggests a mechanism to increase the removal of synaptic serotonin and the low concentrations of serotonin used in these experiments suggest that uptake occurred in the high affinity serotonin uptake pump and can be influenced by ovarian steroids. This is in contrast to the saturation uptake of serotonin which was unaffected by steroids. PMID- 2932202 TI - Differential alterations in opioid analgesia following neonatal monosodium glutamate treatment. AB - Neonatal administration of monosodium glutamate (MSG) produces necrosis of circumventricular structures, including perikarya in the medial-basal hypothalamus that contain beta-endorphin (BEND) and met-enkephalin. Since neonatal MSG treatment alters morphine analgesia, the present study examined neonatal MSG effects upon opioid analgesia observed following either BEND or d ala d-leu enkephalin (DADL). Rats treated with either MSG or vehicle over the first ten post-natal days, were surgically prepared with a lateral ventricle cannula at 100 days of age. Respective groups received central injections of either BEND (0, 0.1, 0.5 or 1.0 microgram) or DADL (0, 4, 20 or 40 micrograms), and jump thresholds were assessed 15, 30, 45 and 60 min thereafter. Following testing, selected MSG-treated and control animals were prepared for BEND immunocytochemistry. While the magnitude, duration and sensitivity of BEND analgesia on the jump test failed to differ between groups, MSG-treated rats displayed a 10-fold leftward shift in sensitivity and a 200-300% increase in the magnitude of DADL analgesia. Immunocytochemical analysis indicated that MSG treatment depleted perikarya in the medial-basal hypothalamus, periventricular thalamic fibers and periaqueductal gray terminal fields that contained BEND. The differential effects of MSG treatment upon opiate and opioid analgesia are discussed in terms of possible alterations in opiate receptor subpopulations. PMID- 2932203 TI - The handicapped child and child abuse. AB - For a group of children with handicaps, growth and development are also affected by abuse or neglect. Our understanding of the problems of the abused, handicapped child emerges from experience with 37 children with cerebral palsy who have been maltreated, coupled with a review of the literature in related areas. We identify the following four problems as crucial to the study of abuse and neglect to the child with handicaps: (1) abuse that causes handicaps, (2) abuse that occurs to the handicapped child, (3) compromises in care that can occur when the handicapped child becomes involved with the medical and legal systems, and (4) arrangements for foster care or other out-of-home placement for the child with handicaps. We conclude that the very systems designed to protect and care for the child often fail, leaving the handicapped child without opportunity to reach developmental potential. In light of our observations, we recommend that the pediatrician not only be aware of the existence of abuse and neglect in the population of handicapped children, but also serve in the dual role of coordinator of services and advocate for these children. PMID- 2932204 TI - [Hemodynamic effects of diazepam, flunitrazepam and midazolam during anesthesia]. PMID- 2932205 TI - Failure of ketanserin, a serotonin inhibitor, to prevent spontaneous or ergonovine-induced attacks of variant angina. AB - Six patients hospitalized with active variant angina were treated for 3 days with the serotonin antagonist ketanserin after a 3 day control period on no medication. The number of variant angina episodes per patient per day was 1.52 +/ 1.42 during the control period and 2.05 +/- 2.30 during ketanserin therapy (p = NS). Ergonovine was administered in incremental doses of 0.0125 mg to 0.4 mg in the control period, during intravenous ketanserin administration and after 3 days of oral treatment. All 6 patients developed ST elevation during all 3 ergonovine tests. The ergonovine dose at which ST elevation developed was similar in each of the 3 periods. It is concluded that ketanserin is of no value in the treatment of variant angina and that both spontaneous and ergonovine-induced coronary spasm in man are unlikely to be mediated by a serotonergic mechanism. PMID- 2932206 TI - On the metabolism of amygdalin. 1. The LD50 and biochemical changes in rats. AB - The mean lethal dose (LD50) of amygdalin in rats was found to be 880 mg/kg body weight (BW) by oral administration. However, when 600 mg/kg BW was administered orally with beta-glucosidase, all the rats died. Total and Mg ATPase activities of the heart decreased with increasing levels of administered amygdalin. When 200 mg/kg BW amygdalin was administered 2.3 mg (11.7% of the dose) was excreted intact over 48 h. Amygdalin, 7.4 mg (18.5% of the dose) was excreted when the dose was 400 mg/kg BW, while 7.5 mg (12.4% of the dose) was excreted as intact amygdalin when the dosage was increased to 600 mg/kg BW. Thiocyanate excreted within the same 48-h period was 7.0, 9.1, and 9.5 mumol representing 18, 11.2, and 7.8% of the 200, 400, and 600 mg/kg BW oral dosage, respectively. With 300 mg/kg BW amygdalin administered intraperitoneally, 4.1 mg amygdalin and 3.9 mumol thiocyanate representing 13.7 and 6.5% of the dose, respectively, was excreted. Excretion of intact amygdalin and thiocyanate was uniform when the dose was low (200 mg), but with higher doses over 70% of the excreted products were detected in the urine during the first 24 h. PMID- 2932207 TI - Effect of endurance swimming on rat cardiac myofibrillar ATPase with experimental diabetes. AB - Diabetes is characterized by depressed cardiac functional properties attributed to Ca2+-activated ATPase activity. In contrast, endurance swimming enhances the cardiac functional properties and Ca2+-activated myofibril ATPase. Thus, the purpose of this study was to observe if the changes associated with experimental diabetes can be ameliorated with training. Diabetes was induced with a single i.v. injection of streptozotocin (60 mg/kg). Blood and urine glucose concentrations were 802 +/- 44 and 6965 +/- 617 mg/dL, respectively. The training control and training diabetic animals were made to swim (+/- 2% body weight) 4 days/week for 8 weeks. Cardiac myofibril, at 10 microM free Ca2+ concentration was reduced by 54% in the sedentary diabetics compared with sedentary control animals (p less than 0.05). Swim training enhanced the Ca2+-activated myofibril ATPase activities for the normal animals. The diabetic animals, which swam for 8 weeks, had further reduced their Ca2+-activated myofibril ATPase activity when compared with sedentary diabetics (p less than 0.05). Similarly, the Mg2+ stimulated myofibril ATPase activity was depressed by 31% in diabetics following endurance swimming. It is concluded that the depressed Ca2+-activated myofibril ATPase activity of diabetic hearts is not reversible with endurance swimming. PMID- 2932208 TI - Occupational asthma: definition, diagnosis and management. PMID- 2932209 TI - Should individuals with anti-HBs as the only marker of infection with hepatitis B receive hepatitis B vaccine? PMID- 2932210 TI - The prevalence of physical disability in southwestern Ontario. PMID- 2932211 TI - Contraception for the older woman--a review. PMID- 2932212 TI - Hepatic arterial and systemic chemotherapy for the treatment of primary and secondary malignancies of the liver. AB - Twenty-two patients with metastatic and primary cancer of the liver were treated with 5-fluoro-2'-deoxyuridine (5FUDR), Mitomycin C (Mito C), and 1 (-2 chlorethyl)-4(methyl-cyclohexyl)-1-nitrosourea (MeCCNU). 5FUDR 0.3 mg/kg/day was administered as a continuous infusion via the hepatic artery. Mito C (10 mg/M2) and MeCCNU (50 mg/M2) were given I.V. and orally, respectively, every 8 weeks. Remission of the neoplastic lesions within the liver was seen in 10 patients (4CR, 6PR). Five patients had stabilization of their lesion neoplasm for at least 4 months. The response rate in this study was 6/15 (40%) in patients with colon cancer metastatic to the liver. Toxicity was mainly hematologic and hepatic. Three patients experienced a platelet count below 25,000 and/or white blood count below 1000. Fifteen patients had hepatic toxicity showing elevation in SGOT and SGPT. The SGOT and SGPT returned to normal when the 5FUDR was discontinued. The combination of 5FUDR intraarterially, and Mito C and MeCCNU systemically, demonstrated activity in malignancies of the liver. This study proved that chemotherapy can be administered systemically and regionally with acceptable toxicity. PMID- 2932213 TI - A phase III trial of oral high-dose medroxyprogesterone acetate (MPA) versus mepitiostane in advanced postmenopausal breast cancer. AB - A randomized controlled trial was performed to compare the therapeutic results of oral high-dose medroxyprogesterone acetate (HD-MPA) versus mepitiostane (MS) in the treatment of postmenopausal breast cancer. MPA was given at three doses of 400 mg orally daily to 47 patients and produced objective responses in 19 cases (40.4%). An objective response was seen in 14 of the 40 control patients given MS at two doses of 10 mg orally daily (35.0%). Among patients with bone metastases, 6 of 19 (31.6%) for HD-MPA and 2 of 13 (15.4%) for MS showed objective responses. The other merits of HD-MPA suggested in the study were improvement in performance status, increase in appetite, and myeloprotective effect. PMID- 2932214 TI - A unique malignant T-cell lymphoproliferative disorder with neutropenia simulating hairy cell leukemia. AB - The association of neutropenia with an indolent chronic T-suppressor cell lymphoproliferative disorder (LPD) has been well documented. The morphologic features and course suggest that this is a benign disorder. The authors studied a 58-year-old man with a chronic T-cell LPD, splenomegaly, and neutropenia. Chromosomal analysis revealed multiple abnormalities which progressively increased in number as the marrow lymphocytosis became more prominent. Subsequently he developed small bowel infiltration. A splenectomy resulted in only brief improvement in the neutropenia. Immunopathologic examination of the spleen was consistent with a well-differentiated lymphocytic lymphoma of a mature peripheral T-cell type without subset specific markers. Granulocyte-monocyte colony (CFU-GM) formation from the patient's marrow was normal and not augmented by T-cell depletion. Neither the patient's splenic T-cells nor serum suppressed granulopoiesis. In contrast to previous T-LPD with neutropenia whose malignant nature has been questioned, the clinical, cytogenetic, and pathologic features and course in this case indicate a malignant lymphoid process which was effectively treated with chemotherapy. Although the histologic pattern of red pulp involvement simulated hairy cell leukemia, that diagnosis was excluded by this patient's clinical, morphologic, and cytochemical features. PMID- 2932215 TI - Diversity of adhesion to basement membrane components of human pancreatic adenocarcinomas. AB - Human carcinomas of the pancreas are aggressive tumors which traverse basement membrane barriers during invasion and metastasis. In order to examine the relationship of pancreatic tumor cells to basement membranes, we analyzed and compared the capabilities of four biologically different human pancreatic adenocarcinoma lines to adhere to substrate coated with purified basement membrane constituents. Each of the four cell lines adhered readily to purified laminin in a dose-dependent manner, although differences were noted in the time required for optimum attachment. Significant variations in the abilities of the cell lines to attach to purified fibronectin were evident both in concentration dependence and in the time required for attachment and spreading. Adhesion to type IV collagen was negligible for two of the four tumor lines but addition of soluble laminin or fibronectin augmented attachment. The other two cell lines attached only moderately to type IV collagen and this attachment was not enhanced by soluble laminin or fibronectin. When laminin or fibronectin was coated directly over type IV collagen, attachment of all four cell lines was comparable to that for the glycoproteins alone. Although the tumor lines were all established from human neoplasms of similar histological origin and retained the ability to adhere to intact basement membranes prepared from human amnion, they exhibited various patterns of attachment to laminin, fibronectin, and type IV collagen. PMID- 2932216 TI - Use of 5-trifluoromethyldeoxycytidine and tetrahydrouridine to circumvent catabolism and exploit high levels of cytidine deaminase in tumors to achieve DNA and target-directed therapies. AB - 5-Trifluoromethyl-2'-deoxycytidine (F3methyl-dCyd), when coadministered with tetrahydrouridine (H4Urd), surpasses the efficacy of 5-trifluorothymidine and 5 trifluoromethyl-2'-deoxycytidine when administered alone as demonstrated with adenocarcinoma 755 and Lewis lung carcinoma as solid tumors implanted in C57BL X DBA/2 F1 mice. It appears that the reason for the heightened efficacy of F3methyl dCyd, when coadministered with low concentrations of H4Urd, is decreased systemic deamination and subsequent systemic catabolism by pyrimidine nucleoside phosphorylases, which do not act on deoxycytidine and its analogues. Furthermore, the elevated levels of cytidine deaminase in these mouse tumors may result in selective conversion of F3methyl-dCyd to 5-trifluorothymidine at the tumor site. This suggests an approach to the treatment of human tumors possessing elevated levels of cytidine deaminase such as certain leukemias, bronchogenic carcinoma of the lung, adenocarcinomas of the colon and rectum, astrocytomas, and certain tumors which are refractory to chemotherapy with 1-beta-D arabinofuranosylcytosine. In contrast to fluorinated pyrimidines in current use, F3methyl-dCyd + H4Urd potentially allows an exclusive DNA-, rather than both a DNA- and RNA-, directed approach. The major mechanism of the antitumor activity of F3methyl-dCyd appears to be via inhibition by 5-trifluorothymidine-5' monophosphate of thymidylate synthetase, the target enzyme of fluoropyrimidine analogues in current use. However, the established and potential differences in the mode of action, anabolism, nature of incorporation into DNA, repair and cofactor requirements of F3methyl-dCyd and its anabolites, compared to that of the commonly utilized fluorinated pyrimidines, indicate that F3methyl-dCyd + H4Urd is a novel combination of agents. In comparative studies with Lewis lung carcinoma, F3methyl-dCyd (+ H4Urd) was shown to surpass the efficacies of 5 fluorouracil and 5-fluorodeoxyuridine and to be essentially equal in efficacy to 5-fluorodeoxycytidine (+ H4Urd). The optimum established protocol against Lewis lung carcinoma is F3methyl-dCyd, 175 mg/kg, + H4Urd, 25 mg/kg, once per day for 7 days. Studies utilizing high concentrations of H4Urd coadministered with F3methyl dCyd indicate that the major pathway of tumor inhibition is via conversion of F3methyl-dCyd to 5-trifluorothymidine in view of the fact that tumor inhibition diminishes at doses of H4Urd which result in extensive (93%) inhibition of tumor cytidine deaminase.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2932217 TI - Metabolism and disposition of menogaril (NSC 269148) in the rabbit. AB - We have investigated the metabolism and disposition, in rabbits, of menogaril (7 OMEN), a new anthracycline antibiotic recently introduced into clinical trials. 7 OMEN was administered by rapid i.v. injection at a dosage of 2.5 mg/kg. 7-OMEN and metabolites were assayed by high performance liquid chromatography. Plasma concentrations of 7-OMEN declined in biexponential fashion with a terminal half life of 2.7 h. The area under the plasma concentration versus time curve was 1.3 microM X h. The systemic clearance of 7-OMEN was 57.6 ml/min/kg. No metabolite of 7-OMEN was detected in plasma. At 8 h after treatment, the cumulative urinary and biliary excretions of 7-OMEN equivalents amounted to 1.3 and 3.4% of the total administered dose, respectively. 7-OMEN was the predominant fluorescent compound in urine, but four metabolites were also seen. In bile, 7-OMEN represented only 9.6% of the cumulative excretion and six metabolites were observed. Among the organs, lungs contained the highest concentrations of parent drug. Substantial concentrations of metabolites were observed in the kidneys, liver, duodenum, and small intestine. Three of the observed metabolites of 7-OMEN have been tentatively identified as N-demethylmenogaril, 7-deoxynogarol, and N-demethyl-7 deoxynogarol. PMID- 2932218 TI - Splenic immune effector and suppressor cells in mice bearing a growing plasmacytoma. AB - The occurrence of tumor immunity in mice bearing a growing plasmacytoma (PC) was studied by local adoptive transfer assay. Spleen cells from mice with a large PC but not with a nonpalpable or small PC retarded and often inhibited entirely the growth of homologous PC. They occasionally caused late regression of growing homologous and heterologous PC. The individual tumor-specific immune effector cells were found to be radiosensitive, non-adherent, Thy 1-positive T-cells. They were resistant to treatment of mice with high-dose cyclophosphamide (CTX). Their generation, however, was abrogated by low-dose CTX and irradiation at the early stage of their development. Spleen cells from PC-bearing mice treated with high dose CTX were enhanced in their effector activity, suggesting the co-existence of CTX-sensitive suppressor cells. The suppressor cells could be demonstrated in spleens of mice bearing a heterologous PC and were found also to be radiosensitive, non-adherent, Thy 1-positive T-cells. Their generation was blocked by treatment of mice with CTX during the early stage of PC development. These findings provide evidence for the occurrence of immune effector T-cells in mice with a growing PC. This immunity appears to be down-regulated by CTX sensitive suppressor cells. PMID- 2932219 TI - Pharmacology of 5'-deoxy-5-fluorouridine in patients with resistant ovarian cancer. AB - The pharmacokinetics of the new fluoropyrimidine 5'-deoxy-5-fluorouridine (5' dFUrd) was investigated in twelve patients. The kinetics of the main metabolite 5 fluorouracil (5-FUra) was studied in eight patients and those of 5,6-dihydro-5 fluorouracil (5-FUraH2) in five patients. The patients participated in a Phase II study performed to investigate the response rate of 5'-dFUrd in advanced ovarian cancer. The pharmacokinetic data were compared with the clinical effects of the drug. The parent drug and 5-FUra were measured in both plasma and urine by high performance liquid chromatography. 5-FUraH2 concentrations in plasma were determined by capillary gas chromatography using electron capture detection and nitrogen-phosphorus specific detection. Several pharmacokinetic parameters such as elimination half-life, mean residence time, and steady state volumes of distribution are presented for 5'-dFUrd, 5-FUra, and 5-FUraH2. Two patients showed a partial response, four had stable disease, and five had progressive disease; one patient died due to myelotoxicity. The severity of the side effects correlated with the mean residence times of 5'-dFUrd and 5-FUra. Low pretreatment serum creatinine clearance (due to renal impairment) correlated with low renal excretion of 5'-dFUrd and a long mean residence time of 5'-dFUrd with the sum of observed toxicity. However, the extent of degradation of 5-FUra to 5-FUraH2 may also be related to the severity of the toxicity of 5'-dFUrd. PMID- 2932220 TI - Inhibition of Streptococcus mutans 6715 glucosyltransferases by sucrose analogs modified at positions 6 and 6'. AB - Sucrose derivatives modified at position 6 (6-deoxysucrose, 6-thiosucrose, 6,6' dithiodisucrose, and 6,6'-dideoxy-6,6'-difluorosucrose) were tested as inhibitors of the two Streptococcus mutans 6715 glucosyltransferases. 6-Deoxysucrose was the best inhibitor studied, competitively inhibiting the soluble-D-glucan forming enzyme (GTF-S) and the insoluble-D-glucan forming enzyme (GTF-I) with Ki values one order of magnitude lower than the sucrose Km values. 6-Thiosucrose was also a competitive inhibitor for both enzymes. 6,6'-Dithiodisucrose and 6,6'-dideoxy 6,6'-difluorosucrose only inhibited GTF-I; 6,6'-dithiodisucrose gave mixed inhibition and 6,6'-dideoxy-6,6'-difluorosucrose gave uncompetitive inhibition. 6 Thiosucrose was a substrate for both enzymes to produce acceptor products when acceptors were present. GTF-I synthesized de novo a water-insoluble, (1----3)-6 thio-alpha-D-glucan from 6-thiosucrose. PMID- 2932221 TI - Radionephrographic follow-up with hypertensive patients after angioplasty of renal artery stenosis. AB - Radionephrographies were performed in 23 hypertensive patients before and after 28 transluminal dilatations (PTD) of their stenosed renal arteries. The changing clearances for both kidneys (global = Clgl) and for stenosed and contralateral kidneys (Clst and Clco) were followed for three groups, dependent on their clinical outcome, as well as the parenchymal transit time (re-entry time) for the diseased (Rtst) and contralateral kidneys (Rtco): (A) Normalized hypertension: for 9 patients the preoperative Clco was never lower than 150 ml/min, but increased significantly after PTD. Rtst fell significantly, Rtco remained constant. Mean increase in Clgl = 91 ml/min (+25%). (B) Improved hypertension: in 12 patients Clst and Clco had been lower than with those in group A; postoperatively Clst increased, Rtst fell significantly. The Rtco was prolonged early after PTD but normalized later. (C) Permanent hypertension: for 7 of these patients there were no preoperative criteria for a discrimination against the other groups. But in all Rtst did not normalize, and Rtco increased early after PTD. Even in later examinations Rtco remained higher than preoperatively. These results imply that the success of PTD depends mainly on the behavior of the contralateral kidney. The examination 1 day after the PTD gives an optimal prognosis concerning the end result. PMID- 2932222 TI - Persistent severe acne. PMID- 2932223 TI - [Occupational dermatoses in the health services]. PMID- 2932224 TI - Small nuclear ribonucleoprotein particle assembly in vivo: demonstration of a 6S RNA-free core precursor and posttranslational modification. AB - The in vivo synthesis and assembly of human small nuclear ribonucleoproteins (snRNPs) have been studied using pulse/chase analysis. Antibodies derived from patients with systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD) recognize distinguishable subsets of pulse-labeled snRNP peptides. These antibodies were used to immunoprecipitate sucrose gradient fractionated pulse-labeled and pulse/chased snRNP proteins. The results indicate that assembly of the U RNA-containing snRNPs is a multistep process involving prior assembly of an RNA-free 6S core particle. This precursor contains snRNP peptides D, E, F, and G, which are common to all the different U RNA-containing particles. Furthermore, a posttranslational modification of one of the U1 snRNP-specific peptides has been observed, and the kinetics of this process indicates that the modification occurs after particle assembly. Functional and structural implications of a protein core for snRNP particles are discussed. PMID- 2932225 TI - Evidence that a phage T4 DNA packaging enzyme is a processed form of the major capsid gene product. AB - A phage T4 DNA packaging enzyme appears to arise as a processed form of the major T4 capsid structural protein gp23. The enzyme activity and antigen are missing from all head gene mutants that block the morphogenetic proteolytic processing reactions of the head proteins in vivo. The enzyme antigen can be formed in vitro by T4 (gp21) specific processing of gp23 containing extracts. Enzyme antigen is found in active processed proheads but not in full heads. The enzyme and the major capsid protein show immunological cross-reactivity, produce common peptides upon proteolysis, and share an assembly-conformation-dependent ATP binding site. The packaging enzyme and the mature capsid protein (gp23*) both appear to arise from processing of gp23, the former as a minor product of a specific gp23 structure in the prohead, acting in DNA packaging as a DNA-dependent ATPase, and a headful-dependent terminase. PMID- 2932226 TI - [Manufacture of bacterial vaccines at the Institute for Sera and Vaccines--the past, present and perspective for the future (on the 60th anniversary of the beginnings of immunologic product manufacture in Czechoslovakia)]. PMID- 2932227 TI - [Molecular biology in the program of the VHJ Institute for Sera and vaccines (on the 60th anniversary of the beginnings of immunologic product manufacture in Czechoslovakia)]. PMID- 2932229 TI - [Antibody response in patients vaccincated with anti-rabies vaccine Vnukovo-32 and HDCV Merieux]. PMID- 2932228 TI - [Immunologic research as reflected in the work of the Institute for Sera and Vaccines (on the 60th anniversary of immunologic product manufacture in Czechoslovakia)]. PMID- 2932230 TI - [A diarrhea epidemic caused by enteroinvasive serotypes of Escherichia coli 028 a,c (Ca792)]. PMID- 2932231 TI - [Lipoteichoic acid in beta hemolytic streptococci]. PMID- 2932232 TI - [Fluorescence tests on cortex Fraxini and its active constituents]. PMID- 2932233 TI - [A new method for the identification of the Chinese drug wu-ling-zhi and its adulterants]. PMID- 2932234 TI - [Microscopic identification of Monetaria annulus and Haliotis discus Hannai]. PMID- 2932235 TI - [Components of essential oils from different parts and the charcoal of Schizonepeta tenuifolia]. PMID- 2932236 TI - [Variations in the alkaloid content of Aconitum carmichaeli before and after processing]. PMID- 2932237 TI - [Technology and quality control of honey pills in Chinese traditional drugs]. PMID- 2932238 TI - [A brief survey of pharmacological studies of Chinese materia medica 1982-1984]. PMID- 2932239 TI - [On a systematic isolation method for hydrophilic constituents of Chinese traditional drugs]. PMID- 2932240 TI - [Preliminary analysis of fresh bamboo juice]. PMID- 2932241 TI - [Pharmacological studies on thirteen kinds of injections from Andrographis paniculata. I. Antipyretic, anti-inflammatory effects and toxicity]. PMID- 2932242 TI - [Experimental studies on action of ginseng flower saponins and ginsenoside Re in gastric ulcers in rats]. PMID- 2932243 TI - [Observations on the biological characteristics of Cornus officinalis]. PMID- 2932244 TI - [A preliminary study on cor pulmonale treated with traditional Chinese medicine and western medicine]. PMID- 2932245 TI - [The effects in chronic cor pulmonale treated with traditional Chinese medicine and western medicine]. PMID- 2932247 TI - [Treatment of the acute stage of cor pulmonale with traditional Chinese medicine and western medicine: a 5-year follow-up]. PMID- 2932246 TI - [Diagnosis and treatment of cor pulmonale with traditional Chinese medicine based on blood gas analysis and acid-base equilibrium: analysis of 202 cases]. PMID- 2932248 TI - [Clinical analysis of 60 cases of ulcerative colitis treated with Chinese traditional medicinal herbs]. PMID- 2932249 TI - [Effects of Rehmannia glutinosa in the treatment of Sheehan's syndrome]. PMID- 2932250 TI - [A clinical study of the relation between thyroxin and the transformation of yang xu symptom-complex in traditional Chinese medicine]. PMID- 2932251 TI - [Clinical experience in treating acute maxillary-facial inflammation by traditional Chinese medicine and western medicine]. PMID- 2932252 TI - [Prevention and treatment of hemorrhage after tooth extraction by using the dry alum powder of Cibotium barometz]. PMID- 2932253 TI - [Treatment of oral leukoplakia with propolis: report of 45 cases]. PMID- 2932254 TI - [Effect of radix Codonopsis pilosulae on cytochemical changes in macrophages]. PMID- 2932255 TI - [Effect of electroacupuncture of the "zusanli" point on the exocrine secretion of the pancreas in rats]. PMID- 2932256 TI - [Experimental observation on the dynamics of common bile ducts obstructed by calculi]. PMID- 2932257 TI - [Current status of the clinical use and experimental study of Salviae miltiorrhizae Bge in the treatment of chronic hepatitis]. PMID- 2932258 TI - [Prevention and treatment of aconite poisoning]. PMID- 2932259 TI - [Necrotizing enteritis due to hypersensitivity reaction (similar to Arthus phenomenon)]. AB - Necrotizing enteritis is a clinico-pathological entity, marked by segmentary necrosis of jejunum and ileum, variously extended, and is a rather rare picture, the etiopathogenesis of which is prevailingly supported by troubles in the intestinal circulation or by intestinal locations of reactions of hypersensitivity (Arthus-similar allergic reaction). The authors start from a case they had the opportunity to observe and successfully surgically treated, and discuss its etiopathogenetic and therapeutical implications in the light of an up to-date reviewing of the literature thereabout. PMID- 2932260 TI - Absence of left ventricular hypertrophy in elite college basketball players. AB - Left ventricular dimensions of 11 successful male college basketball players engaged in pre-season conditioning (mean age, 20.3 years) and 13 tall healthy male controls (mean age, 21.6 years) were studied by echocardiography. Left ventricular internal dimension (LVIDd, mm), posterior wall thickness (PWT, mm), septal thickness (ST, mm), and calculated left ventricular mass (LV mass, g) in the athletes were within or only slightly in excess of echocardiographic normal limits and mean values were not significantly different from the control group. LVIDd (mm/m2 body surface area) was significantly lower in the athletes. However, five guard-type players displayed significantly greater mean values for PWT and LV mass compared to six taller forwards/centers with linear body builds. It was concluded that left ventricular hypertrophy is not a common characteristic of college basketball players. It was hypothesized that cardiac dimensions of young men may vary independently of gross body size in relation to somatotype or other anthropometric variables. PMID- 2932261 TI - Dependency and family care of young adults with disabilities. AB - This paper presents findings on the independence skills of young adults with severe disabilities obtained in a recent survey. Most young people in the sample were heavily dependent on others for help with personal care and mobility. Many also required a considerable amount of supervision because of severe behaviour disturbance. The main burden of daily care was borne by the young adults' mothers. Suggestions are made for fostering independence in self-care and wider social skills. PMID- 2932262 TI - Hemodynamic evaluation of endotoxic shock in anesthetized piglets: antagonism of endogenous vasoactive substances. AB - In anesthetized piglets the influence of an LD100 of Escherichia coli endotoxin (0.5 mg/kg IV, bolus injection) on several hemodynamic parameters and on survival time was studied. Endotoxin provoked a pronounced decrease in arterial pressure and cardiac output and an increase in portal venous and pulmonary arterial pressure and heart rate. Total peripheral and mesenteric vascular resistances displayed an initial increase followed by a sustained decrease, whereas pulmonary vascular resistance revealed a pronounced biphasic increase. All pigs died within 210 min following endotoxin administration. Pretreatment with the 5-HT2 antagonists R 41468 and R 50970 and with the prostanoid-synthesis inhibitor flurbiprofen induced a significant attenuation of the increase in pulmonary vascular resistance and beneficial effects on survival. Best survival results were obtained with prednisolone sodium succinate, although these results can only partly be ascribed to beneficial hemodynamic effects. The experiments with the opiate antagonists, however, point to detrimental effects. PMID- 2932263 TI - Naloxone: ineffective in improving cardiac performance after hypoperfusion in swine. AB - A study was done to measure beta-endorphin immunoreactivity (beta-EI) in swine subjected to cardiopulmonary bypass at normal aortic perfusion pressures and during low-flow states such as can occur with shock. Fifteen pigs, divided into three groups of five each, were placed on total and right heart bypass and perfused as follows: group I, normal blood pressure (80 mmHg); group II, low blood pressure (45 mmHg); and group III, low flows (25 ml/kg/hr). beta-endorphin immunoreactivity was assayed six times during the procedure. Ventricular performance was evaluated by measuring stroke volume (SV) while controlling preload, afterload, and heart rate. Determinations of SV were made at the beginning of bypass, after a 1-hr pump run, and after administration of naloxone (1.1 mg/kg). There were no significant changes in beta-EI in any of the groups during the study. The initial SV in group III (23 +/- 6 ml) decreased significantly (p less than 0.05) after 1 hr of decreased cardiac perfusion (8.0 +/- 7 ml) and was not improved by naloxone (5.0 +/- 7 ml). Ventricular performance was not improved in any group following naloxone administration. In our study, naloxone administered to swine following inadequate myocardial perfusion did not effect a significant cardiac hemodynamic response. PMID- 2932264 TI - Relationship between myosin isoenzyme composition, hemodynamics, and myocardial structure in various forms of human cardiac hypertrophy. AB - Hemodynamic and angiographic parameters, muscle fiber diameter, nonmuscle tissue content, and myosin light chain isoform composition were determined in the left ventricle of nine patients with primary (four with hypertrophic, five with dilated cardiomyopathy) and 27 patients with secondary hypertrophy (11 with aortic regurgitation, 16 with aortic stenosis), nine patients with coronary heart disease, and seven controls. In various forms of hypertrophy, a new atrial-like light chain 1 occurred in two-dimensional electrophoresis of total tissue homogenates amounting up to 29% of total light chain 1. Total light chain 1 content remained constant in all groups when related to tropomyosin. The mean content of this atrial light chain 1 was highest in dilated cardiomyopathy (12.1%), less in cases with pressure (6.4%) and volume overload (2.9%), but as low in hypertrophic cardiomyopathy (0.3%) as in controls (0.4%). In cases with coronary heart disease without prior infarction, it was lower (0.6%) than with infarction (1.9%). Its occurrence was not affected by digoxin administration. In ventricular myocardium, an atrial-like light chain 2 was never observed. Peptide patterns after limited proteolytic digestion of isolated myosin heavy chains from cases with pressure overload and hypertrophic cardiomyopathy were identical to those from controls. The content of the atrial-like light chain 1 was not correlated to either muscle fiber diameter or nonmuscle tissue content, both of which were increased in all hypertrophy groups. In individual cases, no firm correlation could be established between atrial-like light chain 1 content and various parameters of ventricular load and function. However, a significant correlation resulted when the mean values of atrial-like light chain 1 content of each disease group were related to the respective mean values of peak circumferential wall stress (r = 0.96). Thus, the shift of myosin light chain 1 isoforms in ventricle seems to characterize biochemically the hypertrophy process induced by mechanical stress. PMID- 2932265 TI - Carbohydrate interconversions and energy production. PMID- 2932266 TI - Animal preparations relevant for study with positron-emission tomography or nuclear magnetic resonance. PMID- 2932267 TI - Magnetization transfer measurements of creatine kinase and ATPase rates in intact hearts. PMID- 2932268 TI - Determination of dehydroepiandrosterone sulfate in plasma by a one-step enzyme immunoassay with a microtitre plate. AB - We have developed a rapid and cost-effective enzyme immunoassay for dehydroepiandrosterone sulfate (DHEA-S) in plasma, performed with samples on a microtitre plate within 2.5 h. No extraction or centrifugation steps are involved. The 3-hemisuccinate of dehydroepiandrosterone is labeled with horseradish peroxidase, then mixed with hydrogen peroxide substrate in the presence of the chromogen, tetramethylbenzidine. The detection limit of the assay is 12.5 pg of DHEA-S per well. Intra- and interassay CVs at three steroid concentrations (12.8, 1.28, and 0.16 mumol/L) ranged from 2.3 to 5.4% and 6.1 to 8.4%, respectively. Results correlated well (r = 0.95) with those of a radioimmunoassay with iodinated DHEA-S. The turnaround time for 41 samples (in duplicate) is 2.5 h, which includes 2 h of incubation time. The sensitivity of this one-step version and the linearity of its standard curve are equivalent to those of a less practicable two-step version. This technique may replace coated tube enzyme immunoassays for routine use. PMID- 2932269 TI - Diminished interleukin 2 production and receptor generation characterize the acquired immunodeficiency syndrome. AB - The Acquired Immunodeficiency Syndrome (AIDS) is a disease found primarily in homosexual men, consisting of opportunistic infections and tumors, and is due to an acquired T-cell defect. In the present report, we studied various T-cell functions which might serve to distinguish homosexuals with a symptom complex including lymphadenopathy from those with AIDS. T lymphocytes from the lymphadenopathy and AIDS patients had markedly depressed proliferative responses in the autologous (auto) and allogeneic (allo) mixed lymphocyte reaction (MLR) compared to healthy homosexuals or heterosexual controls (P less than 0.001). Since proliferation in the MLR depends upon interleukin 2 (IL-2), a T-cell growth factor, we studied the production of and response to IL-2 in various groups of homosexuals and heterosexual controls. IL-2 production was markedly depressed in the lymphadenopathy and AIDS patients, 1.0 and 0.1 U/ml, respectively, compared to the healthy homosexual or heterosexual controls, both 5.0 U/ml (P less than 0.05 and P less than 0.01, respectively). Although the auto MLR of the lymphadenopathy patients rose to control values with the addition of exogenous IL 2, the auto MLR of the AIDS patients did not (P less than 0.01). This lack of responsiveness to IL-2 in the AIDS group was due to their inability to generate IL-2 receptors as shown by the absence of IL-2 absorption by activated cells and the absence of the Tac antigen (IL-2 receptor) on these same cells. The T4+ and T8+ T-cell subsets from the AIDS patients each demonstrated depressed IL-2 production and responsiveness following activation with autologous cells or mitogen, as well as the absence of Tac antigen. The diminished T-cell proliferation in the auto MLR in the lymphadenopathy group is associated with one defect, low IL-2 production, while the depressed proliferation in the AIDS group is associated with two defects, low IL-2 production and a lack of IL-2 receptor generation. These studies demonstrate that IL-2 receptor generation helps distinguish homosexuals with lymphadenopathy from those with AIDS, and that in addition to T-cell defects in the OKT4+ T-cell subset there are significant abnormalities in the OKT8+ T-cell subset in AIDS patients. PMID- 2932270 TI - Functional properties in Sezary cells with an unusual phenotype. AB - The immunological and functional characteristics of Sezary cells with an unusual phenotype are reported. The clinical, histologic, and hematologic picture was typical for Sezary syndrome. Studies with monoclonal antibodies showed that 80% Sezary cells had an CD3+, CD4+, CD5+, CD7-, CD8-, Leu-7+, Leu-8-, Leu-11-, OKM1- phenotype. By two-color immunofluorescence assay 80% FACS-sorted Leu-7+ cells coexpressed CD4 antigen and did not express the myeloid antigen OKM1, CD8, and antigens characteristic of immature T cells. The cells had no NK activity but did display a high helper activity. Unseparated and FACS-sorted Leu-7+ and Leu-7- Sezary cells did not respond to mitogens but were able to grow in the presence of exogenous IL-2. FACS sorted Leu-7- cells, cultured for 7 days in the presence of 20% IL-2, acquired the receptors for Leu-7. IL-2 and IFN-gamma production was studied in unseparated Leu-7+ and Leu-7- FACS-sorted Sezary cells. IL-2 production was lower than in normal cells. The addition of PHA or PHA plus TPA led to an increase in IL-2 production. Also IFN-gamma production was marked lower than in normal controls but increased after 7-day culture in exogenous IL-2. In conclusion in this case the Sezary cells may represent a neoplastic expansion of the CD3+, CD4+, CD5+, Leu-7+, Leu-11- subpopulation which is equivalent to the 2 4% of the Leu-7+ population in normal lymphocytes. PMID- 2932271 TI - Increased IgG secretion by unstimulated mononuclear cells in active multiple sclerosis and functional assessment of the T8 subset. AB - Unseparated mononuclear cells (10(5) cells/well) were cultured both in the presence and absence of pokeweed mitogen (PWM), and IgG secretion was measured by radioimmunoassay. In unstimulated cultures, levels of IgG secretion were found to be higher in a group of patients with multiple sclerosis (MS) than in control groups of healthy individuals or patients with other neurologic diseases (OND). By contrast, PWM-induced IgG secretion was similar in MS patients and in controls. In MS patients, levels of IgG secretion greater than 2500 ng/ml in unstimulated cultures were present in 29 (58%) of 50 patients with active disease and in only 3 (14%) of 21 patients with inactive MS (P less than 0.01; MS active vs inactive). Furthermore, levels of IgG secretion in unstimulated cultures were higher in patients who had abnormalities of circulating T-cell subsets consisting of reduced numbers of suppressor/cytotoxic (T8) cells and elevated helper:suppressor (T4:T8) ratios. In additional experiments using isolated populations of T-cell subsets, T8 cells from MS patients who had low percentages of circulating T8 cells were found to suppress PWM-induced IgG secretion by autologous cells to a similar extent as controls, suggesting that in vitro, T8 cells function normally in these patients. In vitro IgG secretion by unstimulated mononuclear cells in MS appears to be a further reflection of abnormal immune regulation in this disease. PMID- 2932272 TI - Pulmonary sarcoidosis associated with acquired humoral and cellular immunodeficiency. AB - A previously healthy 27-year-old man with class II pulmonary sarcoidosis developed severe humoral immunodeficiency within the course of the disease with an IgG of less than 250 mg/ml and undetectable levels of IgA and IgM. Repeated skin tests were negative for seven common recall antigens. Cellular blood test demonstrated normal numbers of B cells and slight T-cell lymphopenia with a normal T-helper/suppressor subset distribution (ratio 1.6). In contrast, parallel examination of the bronchial alveolar lavage fluid (BAL) demonstrated highly elevated numbers of T cells with a subset ratio of 3.1 and significant numbers of activated T cells as revealed by the expression of Ia and Tac antigens. Functional in vitro assays showed a greatly decreased mitogenic response of blood T cells and diminished production of immunoglobulins. These data indicate that, despite a severely depressed systemic humoral and cellular immune system, T-cell activation can take place at the inflammatory site, potentially causing the lesions characteristic of sarcoidosis. PMID- 2932274 TI - Cranio-vertebral pathology in Down syndrome. AB - Cranio-vertebral malformations, especially atlanto-axial dislocation, are frequently seen in Down patients. However, symptomatic forms in mongolism are rare. Pyramidal signs have a signal value. In symptomatic malformations surgical treatment should be advised, i.e. posterior fixation after pre-operative reduction by traction or transoral odontoidectomy if no reduction is achieved. PMID- 2932275 TI - Mechanisms of tissue injury induced by immune complexes formed in the circulation or "in situ". PMID- 2932273 TI - Effect of inhibitors of glycosylation and carbohydrate processing on invasion of malignant mouse MO4 cells in organ culture. AB - Inhibitors of glycosylation and carbohydrate processing were used to investigate the role of carbohydrates exposed at the cell surface in invasion. Malignant mouse MO4 cells were confronted with embryonic chick heart in organ culture, an assay shown to be relevant for a number of aspects of invasion in vivo. Tunicamycin (1.0 microgram/ml), 2-deoxy-D-glucose (100 mM), beta-OH-norvaline (1.0 mM), and Monensin (0.1 microgram/ml) reversibly inhibited the invasion of MO4 cells. At these concentrations the drugs also inhibited the growth of MO4 cells. 1-Deoxynojirimycin (10mM), swainsonine (0.4 microgram/ml), and Marcellomycin (0.1 microgram/ml) permitted invasion. Marcellomycin also reversibly inhibited the growth of MO4 cells. These results show that drugs known to interfere with the glycosylation or processing of carbohydrate chains of glycoproteins in different ways have different effects on the invasion of MO4 cells in vitro. PMID- 2932277 TI - Right ventricular hypertrophy and polycythaemia in rats after intermittent exposure to hypoxia. AB - Six groups of 20 male adult rats were maintained in an environmental chamber, each group for a period of 28 days. One group breathed air throughout its experimental period, and a second group breathed a normobaric atmosphere of 12% oxygen. The other four groups were exposed to this hypoxic atmosphere for only a proportion of each 24 h cycle: 2, 4 and 12 h daily, and eight periods of 30 min daily. After 28 days, measurement was made, in each rat, of right ventricule (RV) weight and of red cell mass (RCM) by using 51Cr-labelled rat erythrocytes. In the normoxic control group, RV weight corrected for log body weight in grams was 63.2 +/- 1 mg/log body wt. and RCM was 2.02 +/- 0.05 ml/100 g body wt. This was significantly less than in the group hypoxic for only 2 h each day for 28 days: RV weight 66.6 +/- 0.8 mg/log body wt. (P less than 0.05) and RCM 2.27 +/- 0.05 ml/100 g body wt. (P less than 0.05). Greater increases compared with control were observed in all the other hypoxic groups. There was no significant difference in the increases in RV weight and RCM produced by daily hypoxia in a 4 h continuous period and daily hypoxia in eight 30 min periods. The possible role of intermittent hypoxia in producing polycythaemia and pulmonary hypertension has been the subject of much speculation. Our results show that intermittent hypoxia is a potent stimulus to erythropoiesis and to pulmonary hypertension, reflected in RV hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2932276 TI - Comparison of the expression of terminal deoxynucleotidyl transferase and common acute lymphoblastic leukemia antigen in selected hematologic malignancies. AB - Assays were performed on cells from 38 consecutive malignancies for both terminal deoxynucleotidyl transferase (TdT) and common acute lymphoblastic leukemia antigen (CALLA). TdT and CALLA occurred together only on lymphoblasts from some cases of acute lymphoblastic leukemia (ALL). In other cases of ALL, chronic myelogenous leukemia (CML) in blast crisis, and acute undifferentiated leukemia (AUL), TdT was expressed, but CALLA was absent. TdT was present predominantly on cells from the lymphoid lineage as proven by special histologic stains, and CALLA marked a population with a favorable prognosis. Significant discrepancies in the expression of these two markers and the unique properties of each suggest that both markers are useful for the full characterization of specific hematologic malignancies. PMID- 2932278 TI - [Fibrinolytic treatment today]. PMID- 2932279 TI - Comparison of the membrane-bound (Ca2+ + Mg2+)-ATPase in erythrocyte ghosts from some mammalian species. AB - The properties of the membrane-bound calcium-pumping protein, the (Ca2+ + Mg2+) ATPase (ATP phosphohydrolase, EC 3.6.1.3) were compared in erythrocyte ghosts isolated from five mammalian species--human (Homo sapiens), bovine (Bos taurus), porcine (Sus scrofa melitensis), ovine (Ovis aries crassicandus) and caprine (Capra hircus syriaca). The specific activity of the enzyme in porcine erythrocytes is one order of magnitude higher than in the other species. It was also stimulated to various extents by the regulator protein, calmodulin, and by phosphatidylinositol in all the species. Analysis of membrane proteins revealed a number of differences which seem to suggest that the molecular architecture of the red cell membrane influences the activity of the enzyme. PMID- 2932280 TI - Phosphomannosyl receptors of lysosomal enzymes in cardiac and skeletal muscles of young and old mice. AB - The endogenous activity and the binding of high-uptake beta-N acetylglucosaminidase were assayed in the membranes of heart and skeletal muscles of young (2 months) and old (15 months) NMRI-mice (Mus musculus) to evaluate the age-related changes in the phosphomannosyl receptors of lysosomal enzymes in muscular membranes. The total activities of beta-N-acetylglucosaminidase were significantly higher in cardiac and skeletal muscles of old than young mice. The total and the specific (inhibited by mannose-6-phosphate) binding of beta-N acetylglucosaminidase to the membranes of cardiac muscle, but not to those of skeletal muscle, were higher in old mice than in young ones. The endogenous activity of beta-N-acetylglucosaminidase was significantly higher in the membranes of skeletal muscles of old mice than in those of young mice. The membranes of heart muscles did not show any difference in the endogenous activities. The saturation properties of the binding of beta-N acetylglucosaminidase to the phosphomannosyl receptors were very similar in the membranes of heart and skeletal muscles of both age groups. We conclude that during aging the number of phosphomannosyl receptors of lysosomal enzymes increases in the membranes of heart muscle while the occupancy of phosphomannosyl receptors with endogenous ligands increases in the membranes of skeletal muscle. PMID- 2932281 TI - Disability: upstairs and downstairs. PMID- 2932282 TI - Clinical patterns of hand eczema in women. AB - The hand eczema of 263 women was studied as 4 clinical patterns: palms and fingers, dorsa and fingers, fingers only and the entire hands. The palmar pattern was the commonest. Sensitisers affected the patterns equally but irritants were of less significance in the palmar group than among the rest. Atopics did not appear to have a distinctive pattern. Among the occupational group, irritants were of much greater importance than allergens. PMID- 2932283 TI - Protective effect of gloves--compiled in a data base. AB - In order to be able to give up-to-date and relevant information to those who have to choose and recommend suitable protective gloves, a data base has been developed containing test data on protective effects against chemicals. Permeation data, clinical as well as experimental, have been collected and, after dermatological assessment, inserted into different files in a microcomputer. PMID- 2932284 TI - Lymphocyte subsets and Langerhans cells in allergic and irritant patch test reactions: histometric studies. AB - This study has attempted to distinguish between allergic and irritant reactions to patch tests by semiquantitative histological methods. The extent of perivascular chronic inflammatory infiltrate at 72 h in irritant patch test reactions to sodium lauryl sulphate was shown to be small and very consistent, whereas in allergic reactions to nickel sulphate it was generally larger and more variable in size (p less than 0.02). The two major lymphocyte subsets (T4 and T8) were randomly intermixed in both types of reaction and formed the major component of both the perivascular and diffuse dermal infiltrate, without any evidence of selective migration. The T4:T8 ratios were similar in focal and diffuse infiltrates. The number of T6 dendritic (putative Langerhans) cells in the epidermis (per mm inner epidermal length) was usually greatly reduced in irritant reactions (5-16 mm-1, mean 10 mm-1) but remained within normal limits in allergic reactions (6-33 mm-1, mean 21 mm-1) (p less than 0.001). Comparable results were seen with other irritants (mercuric chloride and benzalkonium chloride) and other allergens (neomycin sulphate, ethylene diamine and potassium dichromate). In additional experiments, pairs of biopsies were taken from the reaction and from adjacent unaffected skin. The T6 cell density in the epidermis did not significantly differ between allergic reactions and control skin. By contrast, the irritant reactions had fewer T6 cells than the control skin (p less than 0.001). PMID- 2932286 TI - Allergic contact dermatitis from diallylglycol carbonate monomer. PMID- 2932285 TI - Elicitation of contact lens allergy to thimerosal by eye cream. PMID- 2932288 TI - Unusual reaction to subcutaneous heparin. PMID- 2932287 TI - Pemphigoid following chronic cement dermatitis. PMID- 2932289 TI - Contact urticaria to strawberry. PMID- 2932290 TI - Occupational contact urticaria from penicillin. PMID- 2932291 TI - Sensitisation to "sensitive teeth" toothpaste. PMID- 2932292 TI - Allergic contact dermatitis to etophenamate. PMID- 2932293 TI - Allergic contact dermatitis to minoxidil. PMID- 2932294 TI - Occupational dermatitis from glass fiber. PMID- 2932295 TI - New data on dermatitis from propolis. PMID- 2932296 TI - Labilin--a little-known contact allergen. PMID- 2932297 TI - Seborrhoeic dermatitis induced by nicotine of horsetails (Equisetum arvense L.). PMID- 2932298 TI - Human sensitization testing with commercial permanent waving lotions containing glyceryl monothioglycolate. PMID- 2932299 TI - A randomized cross-over comparison of two low-dose oral contraceptives upon hormonal and metabolic serum parameters: II. Effects upon thyroid function, gastrin, STH, and glucose tolerance. AB - The effect of a low-dose triphasic oral contraceptive (OC) containing ethinyl estradiol and levonorgestrel (EE/NG) upon thyroid function and some other biochemical serum parameters was compared to that of a preparation containing EE and desogestrel (EE/DG). Blood samples were taken on Day 6, 11, 21, and 28 of a control cycle and of the third cycle of treatment with either the EE/NG or EE/DG preparation (11 volunteers each). After a washout period of 3 months, the contraceptives were changed in a cross-over fashion. Blood samples were again taken on Day 6, 11, 21, and 28 of the third washout cycle and the third treatment cycle. There was a significant increase (13%) in basal glucose level during treatment with both OC, but no change in glucose tolerance. Both the EE/NG and FE/DG preparation elevated serum T4 (40%), FT4 (15-22%), T3 (17-28%), and TBG (20%) significant, whereby the effect was more pronounced during the second treatment period after washing-out. The effective thyroxine ratio (ETR) was slightly (4%) but significantly increased. Contrary to this, the levels of FT3, reverse T3 (rT3), TSH, and gastrin were not altered. STH showed great individual fluctuations, but was significantly elevated by 50% during treatment with both OC. There was no effect of endogenous estradiol upon thyroid or other parameter, even though it was raised considerably in some women under OC. Although the increase in T4 and T3 is probably due to a rise in estrogen-induced TBG production, the data seem to indicate that there is a slight but effective stimulation of thyroid function during treatment with low-dose OC. PMID- 2932300 TI - Two-dimensional echocardiographic evaluation of right ventricular size and contractility in acute respiratory failure. AB - Right ventricular size and contractility were evaluated using two-dimensional echocardiography during the first days of respiratory support in 23 patients requiring mechanical ventilation for acute respiratory failure. Nine patients had normal echocardiographic right ventricular function, and nine other patients had a slightly enlarged right ventricle with normal systolic function. The remaining five patients had a severely enlarged right ventricle with abnormal contractile pattern. In these five patients, two-dimensional echocardiography also showed a reduction in left ventricular size suggesting detrimental ventricular interdependence. All 23 patients had normal left ventricular systolic function by two-dimensional echocardiography. PMID- 2932301 TI - Naloxone therapy of human septic shock. AB - A 0.01 and 0.1-mg/kg dose of iv naloxone was administered to seven patients in septic shock, in order to evaluate naloxone's hemodynamic effect and possible relation to changes in plasma beta-endorphin and catecholamine levels. Naloxone failed to modify cardiac index, blood pressure, heart rate, and systemic vascular resistance. Plasma beta-endorphin, norepinephrine, and epinephrine were elevated but did not change after naloxone administration. These results suggest that beta endorphin release is a consequence but not a cause of shock, and that the beneficial hemodynamic effects of naloxone in animal studies could be related to species differences or nociceptive stimulations. PMID- 2932302 TI - Freeze denaturation of enzymes and its prevention with additives. AB - Freeze inactivation of LDH, MDH, ADH, G-6-PDH, and PK and its prevention with additives such as sodium glutamate and albumin were studied. LDH, MDH, ADH, G-6 PDH, and PK, each lost their activity during frozen storage at -20 degrees C. The speed of the inactivation differed in each. The stability of the enzymes increased with the increase of the enzyme concentration. Sodium glutamate and albumin prevented the freeze inactivation. While the activity of the LDH solution frozen without additives was almost lost during a day of frozen storage, those frozen with either glutamate (0.2 M) or albumin (0.1%) added decreased less quickly. The residual activity after 1 day was 50% the initial prefreeze value for the former and 10% for the latter, respectively. Combined use of glutamate and albumin prevented the inactivation the best and maintained the initial activity almost completely over 6 weeks. The enzymes tested lost some part of their activity when their solutions were diluted by the media. This inactivation was prevented to a significant extent by the addition of sodium glutamate and/or albumin to the diluting media. PMID- 2932303 TI - The use of aztreonam in the treatment of uncomplicated gonorrhoea. AB - A total of 57 men and 26 women with uncomplicated gonorrhoea was treated with 1 g aztreonam intramuscularly. The cure rate was 96% and included successful treatment of 4 infections due to beta-lactamase producing organisms and 8 patients with pharyngeal involvement. The minimum inhibitory concentrations of aztreonam in vitro were lower than those of penicillin and similar to cefuroxime, and side-effects were minimal. It is concluded that aztreonam is effective against Neisseria gonorrhoeae in vivo and in vitro. PMID- 2932304 TI - Increased hepatic microsomal adenosine triphosphatase activity secondary to intra abdominal infection. PMID- 2932305 TI - Genetic analysis of Streptococcus mutans virulence. PMID- 2932306 TI - Contact dermatitis to clotrimazole. AB - A 60-year-old man with allergic contact dermatitis to clotrimazole (Lotrimin) is described. Results of patch tests confirmed the reaction to clotrimazole itself and not the vehicle. After negative results of patch tests to other imidazoles, the patient was treated with econazole without complications. A brief review of contact dermatitis to clotrimazole and other imidazoles is included. PMID- 2932307 TI - A comparison of Cleocin T 1 percent solution and Cleocin T 1 percent lotion in the treatment of acne vulgaris. AB - A randomized, investigator-blind study was conducted to compare the efficacy and skin tolerance of Cleocin T Topical 1 percent Solution and Cleocin T Topical 1 percent Lotion. Both treatments reduced acne lesion counts. More than 70 percent of the evaluable patients receiving each treatment reported that their acne improved by the end of the twelve-week study. Skin dryness was reported significantly more often by patients applying the solution than by those applying the lotion. This newly developed lotion formulation of topical clindamycin phosphate is equal in efficacy to, and appears to be less irritating than, Cleocin T Topical Solution. PMID- 2932308 TI - Isolation and characterization of two repetitive DNA fragments located near the centromere of the mouse X chromosome. AB - Two repetitive DNA fragments located on the mouse X chromosome are described. The fragments were isolated from a lambda phage library enriched in X-chromosomal sequences by flow sorting. Both fragments, which are repeated 20 to 50 times in the genome, were mapped to the mouse X chromosome by Southern blot hybridization to DNA from hybrid cells retaining the mouse X chromosome, by dosage analysis, and by in situ hybridization to mouse chromosomes. In mouse strain C57BL/10BK, one fragment appeared to be located only on the X chromosome, while the other fragment had homologous sequences on chromosome 11 in addition to the X chromosome. The latter fragment showed DNA variants between mouse strains, which are potentially useful for mapping. Both fragments cross-hybridized to another mouse species: Mus caroli. In this species, each fragment appeared to be located on the X chromosome, indicating that some X-chromosome repetitive sequences are partially conserved. In addition, one fragment cross-hybridized to human DNA. PMID- 2932309 TI - [Animal experiment and clinical application of Bletilla striata as an embolizing agent]. PMID- 2932310 TI - [An experimental study on the mechanism of gastrointestinal double contrast image formation and its clinical application]. PMID- 2932311 TI - [CT diagnosis of intracranial epidermoid cyst]. PMID- 2932312 TI - [The left ventriculography in endocardial cushion defect]. PMID- 2932313 TI - [Selective superior mesenteric arteriography in the diagnosis of intestinal tumors and intestinal bleeding]. PMID- 2932314 TI - [Observation of the middle meningeal sinuses in the Chinese]. PMID- 2932315 TI - [Investigation on the radiological anatomy of the Runstrom II projection of the temporal bone]. PMID- 2932316 TI - [Skeletal changes in congenital dysgenesis of the ovary (a report of 10 cases)]. PMID- 2932317 TI - [An X-ray follow-up of Kaschin-Beck's disease after leaving endemic areas]. PMID- 2932318 TI - [Laparoscopy performed with gastroscopy]. PMID- 2932319 TI - [Concanavalin A-induced suppressor cell activity in patients with leukemia]. PMID- 2932320 TI - [Studies of the physical measurements and health status of Down's syndrome patients]. PMID- 2932321 TI - Modification of silastic sling repair for rectal procidentia and anal incontinence. PMID- 2932323 TI - Prostaglandins and chemotherapy-induced ulcers in dogs. AB - About 50% of patients receiving intrahepatic infusion of 5-fluorouracil deoxyriboside (5-FUDR) for colorectal cancer with hepatic metastasis develop significant gastroduodenal lesions. This paper reviews two studies on the effect of 16,16 dimethyl prostaglandin E2 (DMPGE2) on 5-fluorouracil-induced mucosal lesions in dogs. DMPGE2 at high doses (2 micrograms X kg-1 X h-1), which reduced histamine-stimulated gastric acid secretion by 65%, reduced gastric mucosal injury. Interestingly, DMPGE2 at much lower doses (0.02 micrograms X kg-1 X h-1), which had no effect on histamine-stimulated gastric acid secretion, was also effective in lowering gastric mucosal injury. These animal studies, if supported by the results of a larger patient study, would provide a rational basis for the use of prostaglandins in the prophylaxis and treatment of chemotherapy-induced ulcers. PMID- 2932322 TI - Influence of ranitidine on hepatic blood flow assessed by organ-reflectance spectrophotometer and pulse-Doppler ultrasonic flowmeter. AB - The influence of the intravenous injection of ranitidine (50 mg) on hepatic hemodynamics was investigated in normal subjects and patients with chronic liver disease. Using the organ-reflectance spectrophotometer, the regional hepatic blood hemoglobin concentration (delta Er569-650), an indicator of the regional hepatic blood flow, and the oxygen saturation of hemoglobin in the regional hepatic tissue (So2) were measured in patients with chronic liver disease after ranitidine injection under peritoneoscopy. With the pulse-Doppler ultrasonic flowmeter, the portal blood flow was measured in patients with chronic liver disease and normal subjects. There were no significant changes in the regional hepatic blood flow, the oxygen saturation of hemoglobin, and the portal blood flow after the intravenous injection of ranitidine. Thus, it is concluded that usual dose of ranitidine has no significant influence on the hepatic blood flow and that it can be prescribed without reducing the hepatic blood flow. PMID- 2932324 TI - Gastroduodenal bicarbonate secretion in mucosal protection. Possible role of vasoactive intestinal peptide and opiates. AB - HCO3- secretion by surface epithelium in duodenum devoid of Brunner's glands was titrated in situ in anesthetized rats. Intravenous injection of small amounts (20 ng/kg) of the endogenous opioid peptide beta-endorphin significantly increased secretion. Naloxone prevented this effect, suggesting that stimulation is mediated by mu-opiate receptors. Morphine 50 microgram/kg had a similar stimulatory action. Vasoactive intestinal peptide (VIP) 0.5-100 microgram/kg dose dependently increased secretion and this response was independent of simultaneous cholinergic stimulation. The HCO3- secretion maintained pH in the mucus gel adherent to the luminal surface at neutrality for long periods of time (greater than or equal to 60 min); even when the pH in the terminal bulk solution was as low as 2.0. Mucosal HCO3- secretion is thus very probably important in mucosal protection and VIP and endogenous opioid peptides may have a role in its control. PMID- 2932325 TI - Action of drugs and chemical agents on rat liver regeneration. AB - Chemical agents and drugs of widely differing pharmacological activity have been administered to partially hepatectomized male rats and the extent of liver regeneration ascertained over a period of 10 days. Of the large number investigated, the following fed ad lib in diets supplemented in a basal ration at the weight percentages indicated, proved to be hepatotrophic: anticonvulsants - mephenytoin (0.15), methsuximide (0.15), phensuximide (0.15) and primidone (0.10); benzodiazepines - clobazam (0.10), flurazepam hydrochloride (0.12), halazepam (0.070), oxazepam (0.030) and temazepam (0.10); anti-inflammatory agents - benoxaprofen (0.040), ibuprofen (0.10 and 0.20), naproxen (0.040) and sulindac (0.075); sedatives and hypnotics - ethinamate (0.75), glutethimide (0.075), methaqualone (0.030 and 0.10) and methprylon (0.30) and the analgesic and antipyretic, aminopyrine (0.15); antifungal - griseofulvin (0.50); anti androgen - cyproterone acetate (0.020 and 0.050); uricosuric - sulfinpyrazone (0.050 and 0.20); skeletal muscle relaxant - chlorzoxazone (0.20); hydrocholeretic - florantyrone (0.30); anti-hypertensive - prazosin hydrochloride (0.010) and the thyroid inhibitor, methimazole (0.025). The feeding of several of the stimulants at the given levels to intact males elicited wet and dry liver enlargement. Most of the current test agents as screened in operated rats, had little effect on the regeneration and in fact, tended to depress the process when higher levels were fed or injected. PMID- 2932326 TI - Dermatitis. AB - Dermatitis, the inflammatory response of the skin to various factors, may present in a variety of forms. Atopic dermatitis, contact dermatitis, nummular eczema, seborrhea, and stasis dermatitis, conditions with which the patient may present to the emergency department, either in the acute stage or with exacerbation of a chronic condition, are reviewed in this article. PMID- 2932327 TI - Drug eruptions in an emergency department setting. AB - The author outlines specific methods of evaluating drug reactions in terms of the appearance of the reaction and then lists the drugs likely to produce these reactions. Proposed mechanisms of these reactions are also discussed. PMID- 2932328 TI - Peritoneoscopic placement of a Tenckhoff catheter for chronic peritoneal dialysis. AB - The use of peritoneoscopic control in the placement of a Tenckhoff catheter for chronic peritoneal dialysis permits accurate positioning of the catheter. As a result, the risk of malfunction during change of dialysis fluid is considerably reduced, and prior abdominal surgery and adhesions no longer automatically represent contraindications. A special trocar permits the introduction of the catheter to be done more gently, causes less scarring, and does away with the lower Dacron cuff. This prevents the kinking of the catheter in the abdominal wall, and makes the change of dialysis fluid more convenient. In addition, the procedure takes less time to carry out, as does the removal of the catheter on termination of dialysis. PMID- 2932329 TI - Influence of ethanol on the human serum level of beta-hexosaminidase. AB - Serum activities of the lysosomal enzymes beta-hexosaminidase, alpha-fucosidase and alpha-mannosidase in teetotalers, healthy persons with 'ordinary' alcohol consumption, chronic alcoholics and patients with alcoholic liver cirrhosis were compared. There was no difference between controls and teetotalers, whereas serum from chronic alcoholics and patients with alcoholic liver cirrhosis showed a significant increase of lysosomal enzymes compared to controls and teetotalers. The effect of daily alcohol ingestion on the serum activity of lysosomal enzymes was studied in 9 healthy volunteers. A minor but significant increase was found for beta-hexosaminidase. It is concluded that the increase of lysosomal enzyme activity in serum from alcoholics is due to the liver dysfunction. PMID- 2932330 TI - A controlled evaluation of paraspinal EMG biofeedback in the treatment of chronic low back pain. AB - Sixty-six chronic low back pain sufferers were randomly divided into three groups. Following individual assessments consisting of psychological questionnaires, pain monitoring, and measurement of paraspinal electromyogram (EMG), one group received paraspinal EMG biofeedback and another a placebo treatment. The third group received no intervention. Two further assessments were carried out on all groups immediately after treatment and at a 3-month follow-up. All groups showed significant reduction in pain, anxiety, depression, and paraspinal EMG following treatment and at follow-up, but there were no differences between groups. A regression analysis failed to identify subjects' characteristics that predicted positive outcome in the biofeedback group. However, high scores on the Evaluative scale of the McGill Pain Questionnaire and high hypnotizability were significant predictors of positive outcome for the placebo group. It is concluded that paraspinal EMG biofeedback is not a specific treatment for chronic low back pain in a nonhospitalized population. PMID- 2932331 TI - Isolation and structural organization of the Neurospora crassa copper metallothionein gene. AB - The Neurospora crassa copper metallothionein gene was cloned and its complete nucleotide sequence is reported. Enriched metallothionein mRNA was used as a template for cDNA synthesis, primed by a metallothionein-specific, synthetic undecanucleotide. The sequence of the cDNA obtained allowed the synthesis of a unique 21-mer which was used to screen a genomic DNA library of N. crassa. In agreement with the published amino acid sequence, the gene codes for a polypeptide 26 amino acid residues in length. The coding region is interrupted by a small intron (94 nucleotides). The gene structure is compared with those of mammalian metallothioneins. In both cases, the coding regions are split by introns, the intron-exon boundaries, however, are in different positions. The neurospora copper metallothionein gene is, to our knowledge, the smallest gene interrupted by an intron isolated so far. PMID- 2932332 TI - Em polypeptide and its messenger RNA levels are modulated by abscisic acid during embryogenesis in wheat. AB - The effect of abscisic acid (ABA) on the expression of the 'early-methionine labeled' (Em) polypeptide was examined in cultured, immature wheat (Triticum aestivum, L.) embryos and in developing embryos in planta. A complementary DNA (cDNA) library was constructed from poly(A)-rich RNA from immature embryos cultured in the presence of ABA. ABA-enhanced sequences were first identified by differential colony-blot hybridization, and then verified using RNA slot-blot analysis. Dot-blot hybridization showed that one clone, p1015, was homologous to the previously isolated Em cDNA, pWG432. Electrophoretic analysis of the hybrid select translation product of p1015 confirmed its identity as an Em sequence. Comparison of the p1015 cDNA insert size and the Em message size, from northern blot analysis, showed that p1015 contained about 87% of the Em sequence. RNA slot blot analysis and protein electrophoresis showed that Em message, but not Em protein, accumulated at a low, basal level in immature embryos in the absence of ABA. Neither Em message nor Em protein was seen in three-day germinated seedlings. Steady-state levels of Em message and protein increased in immature embryos in the presence of ABA, both in culture and in planta. Regulation appeared to be primarily at the level of transcription or specific message stability. Regulation may also involve specific protein stability, since synthesis of Em protein continued in immature embryos in the absence of ABA, but Em protein did not accumulate in detectable amounts. We conclude that ABA specifically modulates Em message and protein levels in immature embryos, but is probably not responsible for the embryogenic specificity of Em expression. PMID- 2932333 TI - DNA sequence analysis of the oli1 gene reveals amino acid changes in mitochondrial ATPase subunit 9 from oligomycin-resistant mutants of Saccharomyces cerevisiae. AB - The nucleotide sequence of the oli1 gene encoding mitochondrial ATPase subunit 9 (76 amino acids) has been determined for five oligomycin-resistant mutants of Saccharomyces cerevisiae. Three of the mutations affect amino acids in the vicinity of the glutamic acid residue 59 at which dicylohexyl carbodiimide binds. Two other mutations lead to substitution of amino acid 23, which would lie very close to residue 59 in the folded hairpin conformation that this protein is thought to adopt in the inner mitochondrial membrane. The apposition of residues 23 and those adjacent to residue 59, lying respectively in the two hydrophobic membrane-spanning arms of subunit 9, is considered to constitute an oligomycin binding domain. By consideration of the amino acid substitutions in those mutants cross-resistant to venturicidin, a domain of resistance for venturicidin is defined to lie within the oligomycin-binding domain, also centered on residues 23 and 59. These data also clarify the genetic recombination behaviour of alleles previously defined to form part of the oli3 locus (mutants characterized by resistance to both oligomycin and venturicidin) together with alleles defined to form part of the oli1 locus (mutants not cross-resistant to venturicidin). The oli1 and oli3 loci can now be seen to form two overlapping extended groups within the oli1 gene, with sequenced oli3 mutations being as far apart as 125 nucleotides within the subunit 9 coding region of 231 nucleotides. PMID- 2932334 TI - Dose dependent pharmacokinetics of midazolam. AB - The pharmacokinetics of midazolam and 1-hydroxymethylmidazolam were investigated following oral administration of 7.5, 15 and 30 mg doses of midazolam in solution to 12 healthy subjects. Compared to the 7.5 mg dose, the Cmax and AUC parameters of both midazolam and 1-hydroxymethylmidazolam increased proportionally after the 15 mg dose and more than proportionally after the 30 mg dose. The t1/2 for midazolam remained relatively constant between the 7.5 and 15 mg doses whereas it increased slightly but significantly after the 30 mg dose. These data indicated that the pharmacokinetics of midazolam and 1-hydroxymethylmidazolam were linear between the 7.5 and 15 mg oral dose range. However, after the 30 mg dose, the systemic availability of midazolam and the AUC for 1-hydroxymethylmidazolam appeared to be greater than that anticipated from the lower doses, possibly due to saturation of midazolam first-pass metabolism. This is not expected to have any clinical significance under the conditions of therapeutic use. PMID- 2932335 TI - Ontogenic development of "natural" and induced plaque-forming cell isotypes in normal mice. AB - The numbers of cells and background plaque-forming cells (PFC) in the spleen of C3H/HeJ mice increase exponentially during the first 2 weeks after birth, but much slower in bone marrow (BM). IgG1 and IgG2a PFC are the first non-IgM PFC detectable, while IgG3 and IgA PFC appear only around weaning. Adult-type PFC numbers and isotype pattern are present in spleen and BM at 4 and 15 weeks, respectively. Neonatal splenic C3H/Tif B cells produce non-IgM Ig classes in vitro in response to polyclonal activation by lipopolysaccharide or by helper T cells. These responses are of low magnitude during the first 2 weeks of life, but both secreted and membranebound IgG1 and IgG3 isotypes are detectable already a few days after birth, in a pattern that is identical to that typical of T cell dependent or independent responses of adult cells. These results indicate full maturity of B cells in "switch" abilities already from birth, in spite of a general deficiency in terminal maturation. In addition, they demonstrate the complexity of isotype regulation in "background" antibody production in vivo. PMID- 2932336 TI - The ability of Ia and H-2Kk-bearing membranes to replace the antigen-presenting cell in an H-2Kk allogeneic cytotoxic T cell response. AB - Induction of an allogeneic cytotoxic T lymphocyte (CTL) response is dependent, in part, on uptake and processing of the class I alloantigen by antigen-presenting cells and subsequent Ia-restricted recognition of the alloantigen by helper T cells, resulting in lymphokine production. The nature of the antigen-processing event has been investigated using reconstituted membranes to replace the antigen presenting cells in the generation of a secondary allogeneic CTL response. Membranes were isolated from an Iad-positive antigen presenting B cell lymphoma (D2N), detergent solubilized and then reconstituted together with affinity purified H-2Kk antigen in the presence of protease inhibitors. These reconstituted vesicles, containing both syngeneic Ia and alloantigen, were able to induce the helper T cell arm of the CTL response in cultures depleted of antigen-presenting cells. A variety of control experiments provided strong evidence that the helper T cells recognized the H-2Kk, probably in its native form, in an Ia-restricted manner on the vesicles, while the pre-CTL can directly recognize H-2Kk. Recognition was only effective if both the Ia and alloantigen were inserted into the same membrane bilayer. The results strongly suggest that the obligatory antigen processing event required for helper T cell recognition of alloantigen is simply the insertion of the alloantigen into the same membrane bilayer as the syngeneic Ia restricting element. PMID- 2932337 TI - Dominant suppressive effect of the silent Eb alpha allele on an in vivo T helper cell response under Ed beta Ed alpha region-linked immune response gene control. AB - Previous adoptive spleen cell transfer experiments have demonstrated that an immune response (Ir) gene linked to the Ed beta Ed alpha region allows BALB/c T helper lymphocytes (Th) to respond to an idiotope on the V lambda 2(315) fragment of isologous myeloma protein M315. BALB.K (H-2k) and BALB.B (H-2b) do not respond to V lambda 2(315). While (H-2d X H-2k)F1 hybrids have been shown to be responders, it is now demonstrated that (H-2d X H-2b)F1 hybrids are low responders. By crossing BALB/c with various H-2 recombinants on B10 background and probing Th responsiveness to V lambda 2(315) in these F1 hybrids, the dominant suppressive gene of the H-2b haplotype is mapped to Eb alpha Sb. It is argued that the suppressive gene is Eb alpha, which is a silent allele. A likely explanation for the suppressive effect of the Eb alpha allele is that reduced amounts of Ed beta: Ed alpha restriction elements are present on antigen presenting cells of (H-2d X H-2b)F1 hybrids because only one E alpha gene is functional in such mice. The present report extends previous in vitro findings from other laboratories to the in vivo situation and suggests that silent alleles for class II molecule chains may profoundly affect certain immune responses of individuals heterozygous for the silent allele. PMID- 2932338 TI - Antigen-specific major histocompatibility complex-restricted helper T cell clones are sufficient to induce unprimed B cells to switch and to secrete IgG and IgA in a primary in vitro polyclonal response. AB - To investigate the role of helper T (Th) cells in the regulation of the production of the various immunoglobulin (Ig) classes and subclasses, we have used poly (Glu60 Ala30Tyr10) (GAT)-specific, major histocompatibility-complex restricted Th cell clones to stimulate unprimed B cells. The T cells used in these studies were Thy-1+, Lyt-1+, Lyt-2- and lacked Fc receptor for IgM, IgG and IgA, and the unprimed splenic B cells were selected by the fluorescence-activated cell sorter for their lack of expression of surface (s)IgG and by panning for their lack of expression of sIgA. We have taken advantage of the ability of some antigen-specific major histocompatibility complex (MHC)-restricted Th cell clones to polyclonally activate unprimed B cells in vitro in the presence of high doses of antigen. We have shown that under these conditions, an antigen-specific MHC restricted Th cell clone is sufficient to induce the switch of sIgG- sIgA- unprimed B cells to IgG and IgA, as well as the expansion of these cells and their differentiation into IgG and IgA-secreting cells. Isotype-specific Th cells thus do not seem to be an absolute requirement for the production of the various IgG subclasses and of IgA. PMID- 2932339 TI - A subset of OKT4+ peripheral T cells can generate colonies containing mixed progeny with OKT4+ helper and OKT8+ suppressor cells. AB - The membrane phenotype of human T cell colony progenitors and that of their clonal progeny was studied for expression of the T4 and T8 determinants. Using clonal culture conditions, the colonies were grown in semi-solid agar medium from peripheral blood cells. Clonality was assessed using the glucose-6-phosphate dehydrogenase isoenzyme marker. Combination of this marker with the culture of sorted cell fractions allowed us to ascribe the colony progenitors to a subset of OKT4+ lymphocytes. The progeny consisted of the mixture of single OKT4+, single OKT8+ and double OKT4+8+ cells, as determined by double staining. Double staining was performed on mass-harvested colony cells and on individual colonies expanded in liquid culture with fresh interleukin 2. Expression of the OKT8 positivity on colony cells deriving from OKT4+ progenitors required an interaction with radioresistant OKT8+ cells that were co-cultured with these progenitors. Furthermore, the functional capacities of the cell progeny were assayed on the pokeweed mitogen-driven immunoglobulin production by B cells. It was found that OKT4+ colony cells were helper whereas OKT8+ colony cells were suppressor cells. It is concluded that a subset of OKT4+ peripheral blood T lymphocytes can generate colonies containing both helper OKT4+ cells and suppressor OKT8+ cells. PMID- 2932340 TI - Modulation of complement receptors of a human monocyte cell line, U-937, during incubation with phorbol myristate acetate: expression of an iC3b-specific receptor (CR3). AB - The human monocyte line, U-937, derived from an individual with histiocytic lymphoma was studied for the expression of surface C3 receptors, after cultivation in the presence of phorbol myristate acetate (PMA) or T lymphocyte conditioned medium. Receptors were detected by using EAC4b, EAC3b, EC3b, EAC3bi and EAC3d intermediates. U-937 cells, in exponential growth phase, poorly bound the intermediates; after exposure to PMA or T lymphocyte-conditioned medium, U 937 cells strongly bound both EAC3b and EAC3bi since about 50% of cells rosetted with these intermediates. This binding was totally inhibited by EDTA and by Mac-1 monoclonal antibody, suggesting the presence of only CR3 receptor types on these cells. Although U-937 cells formed rosettes with EAC3b, there was no evidence for the presence of CR1 receptors since no rosette was observed either with EAC4b or with EC3b intermediates (EC3b were prepared by coupling purified C3b to erythrocytes with N-succinimidyl 3-(2-pyridyldithio)propionate. As small amounts of factor H were present on EAC3b intermediates, incubation of EAC3b with U-937 cells induced their transformation into EAC3bi and their binding to CR3. Moreover, U-937 cells did not promote the cleavage of C3b in the presence of factor I alone, suggesting that these cells did not bear a sufficient amount of functionally active CR1. These results demonstrated that U-937 cells predominantly expressed CR3. The study of the kinetics of EAC3bi rosette formation demonstrated that CR3 expression is closely related to PMA activation. We suggest that CR3 activity could result from a phosphorylation of existing receptors. PMID- 2932341 TI - Functional differences between B cell-depletion techniques in removing memory B cells. Relevance to anti-erythrocyte autoantibody-specific suppressor cells. AB - The efficiency of a number of B cell-depletion techniques was examined in a functional assay. CBA (Iga) mice were primed with rat erythrocytes and their spleen cells transferred, before and after B cell depletion, to mice of the allotype-congenic strain Igb. The recipients were challenged with rat erythrocytes and their anti-erythrocyte autoantibody response was measured together with the donor (Iga) and host (Igb) anti-rat erythrocyte antibody levels. Transferred unseparated cells suppressed erythrocyte autoantibodies and produced high levels of anti-rat erythrocyte antibodies. Transfer of panned, rosetted or nylon wool-passaged cells neither altered donor anti-rat erythrocyte antibody levels nor abrogated suppression. By contrast, passage of rat erythrocyte-primed B cells over Ig-anti-Ig-coated beads resulted in removal of donor rat-primed B cell activity and loss of suppressor cells. The B cell depletion techniques were effective at removing B cells as judged by the reduced number of fluoresceinated anti-Ig-labeled cells among unbound cells although analysis on a fluorescein-activated cell sorter revealed that the most effective method was depletion on Ig-anti-Ig-coated beads. B cell depletion by panning removed the capacity of virgin but not primed cells to make adoptive antibody responses after transfer suggesting that the primed cells most efficient in adoptive transfer have a lower density of surface Ig than virgin cells. Treatment of donors with drugs which abrogated transferrable suppression of erythrocyte autoantibodies did not alter donor anti-rat erythrocyte antibody levels in recipients. It is considered that rat primed B cells are involved in the suppression of erythrocyte autoantibodies by acting as selective antigen presenting cells for T suppressor inducer cells, rather than through an anti-rat erythrocyte antibody feedback mechanism. PMID- 2932342 TI - Specific binding of [3H]d-cis-diltiazem to cardiac sarcolemma and its inhibition by calcium. PMID- 2932343 TI - Spiperone differentiates multiple 5-hydroxytryptamine responses in rat hippocampal slices in vitro. PMID- 2932344 TI - Transmembrane calcium movement in 20,25-diazacholesterol myotonia. AB - An abnormality in myoplasmic Ca2+ regulation has frequently been proposed in 20,25-diazacholesterol (20,25-D) myotonia. We report here the results of several studies of transmembrane Ca2+ movement in this animal model. (i) Physiologic Ca2+ release by intact sarcoplasmic reticulum (SR) was examined in chemically skinned single muscle fibers preloaded in EGTA-buffered Ca2+ solutions (pCa2+7.0 to 6.4). Isometric tension development and Ca2+ release thresholds in response to Cl- or caffeine showed no differences between control and 20,25-D fibers at any pCa2+. (ii) The kinetics of energy-dependent Ca2+ accumulation in purified SR vesicles were followed spectrophotometrically using Ca2+-sensitive dyes. The apparent rate for ATP-dependent Ca2+ uptake and Ca2+ sequestering capacity were unchanged in SR from 20,25-D animals vs. controls. (iii) Surface membrane Ca2+ATPase activity was measured in red blood cell ghosts and sarcolemma. Enzyme Vmax was decreased by 25 to 50% in both membranes in the 20,25-D-treated animals with a compensatory increase in the number of Ca2+ATPase molecules. In general, the SR handling of Ca2+ appears normal in 20,25-D myotonia, although the activity of Ca2+ATPase in membranes with high sterol content may be altered in response to changes in the lipid environment in this model. PMID- 2932345 TI - Bundling of actin filaments by aorta caldesmon is not related to its regulatory function. AB - Ca2+-sensitive thin filaments from vascular smooth muscle were disassembled into their constituent proteins, actin, tropomyosin and caldesmon. Caldesmon bound to both actin and to actin-tropomyosin and inhibited actin-tropomyosin activation of skeletal muscle myosin MgATPase. It also promoted the aggregation of actin or actin-tropomyosin into parallel aligned bundles. Quantitative electron microscopy measurements showed that with 1.1 microM actin-tropomyosin, 1.6 +/- 0.5% (n = 3) of the filaments were in bundles. At 0.073 microM, caldesmon inhibited MgATPase activity by 50%, whereas bundling was 3.0 +/- 1.3% (n = 4). At 0.37 microM caldesmon, MgATPase inhibition was 83% while 28.1 +/- 6.9% (n = 4) of filaments were in bundles. Experiments at 4.4 microM in which MgATPase and bundling were measured in the same samples gave similar results. Small bundles of 2-3 filaments showed the most frequent occurrence at 1.1 microM actin. At 4.4 microM actin the most common bundle size was 3-5 filaments, with the occasional occurrence of large bundles consisting of up to 120 filaments. The incidence of bundling was the same in the presence and absence of tropomyosin. Thus caldesmon can induce the formation of actin bundles but this property bears no relationship to its inhibition of MgATPase activity. PMID- 2932346 TI - Caldesmon-induced inhibition of ATPase activity of actomyosin and contraction of skinned fibres of chicken gizzard smooth muscle. AB - Caldesmon induces inhibition of MG2+-ATPase activity of actomyosin and relaxation of skinned fibers of chicken gizzard smooth muscle without influencing the level of myosin light chain-1 phosphorylation. Both these effects are reversed by calmodulin at a high molar excess over caldesmon in the presence of Ca2+. PMID- 2932347 TI - [Chromosome disease. I. Autosomal syndromes]. PMID- 2932348 TI - The effects of ovarian adhesive disease upon follicular development in cycles of controlled stimulation for in vitro fertilization. AB - This study was designed to determine the effect of periovarian adhesive disease upon follicular development. Forty-one clomiphene citrate/human menopausal gonadotropin/human chorionic gonadotropin-stimulated cycles for in vitro fertilization and embryo transfer were studied. Each patient was assessed ultrasonographically before laparoscopic oocyte recovery. The number of follicles in each ovary greater than 1.2 cm was counted. By laparoscopy it was possible to determine the degree of periovarian adhesive disease. Sixteen patients had bilateral adhesion-free (AF) ovaries, 12 had bilateral adherent (A) ovaries, and 13 had one AF and one A ovary. In the 13 patients with one ovary AF and the other A, the mean number of follicles +/- 1 standard deviation (SD) was 3.4 +/- 1.4 and 1.2 +/- 1.1 (P less than 0.001), respectively. A total of 116 follicles was noted in 45 AF ovaries (mean +/- 1 SD, 2.6 +/- 1.3) and 59 follicles in 37 A ovaries (mean +/- 1 SD, 1.6 +/- 1) (P less than 0.001). From these data it was concluded that the presence of periovarian adhesive disease inhibits folliculogenesis by a yet undetermined mechanism. PMID- 2932349 TI - Treatment of endometriosis with a potent agonist of gonadotropin-releasing hormone (nafarelin). AB - Administration of superactive agonistic analogs of gonadotropin-releasing hormone (GnRH) has been shown to induce a paradoxic and reversible suppression of gonadotropins, resulting in suppressed gonadal steroid concentrations. Because there currently is no uniformly successful and acceptable medical therapy for endometriosis, we examined the effects of 6 months of nasal administration (500 micrograms every 12 hours) of the agonistic analog of GnRH, nafarelin, on clinical signs and symptoms and hormonal profiles in eight women with endometriosis. All patients had prompt and near-complete relief from their painful symptoms of endometriosis. Laparoscopy or laparotomy, performed both before and after treatment in seven of the women, revealed complete resolution of active endometriotic lesions in five patients and only a single, small cul-de-sac implant in a sixth woman. A large ovarian endometrioma decreased slightly in response to treatment in the seventh woman. Serum luteinizing hormone and follicle-stimulating hormone concentrations, after a transitory stimulation at the onset of treatment, declined and were suppressed (P less than 0.001) during the remainder of treatment. Serum estradiol concentrations fell to approximately menopausal levels (less than 30 pg/ml) after 1 to 4 weeks. Reversibility of drug effect was prompt, with ovulatory menses returning 47 +/- 8 days (+/- standard deviation) after treatment. Thus, nasal administration of agonistic analogs of GnRH may represent a new treatment modality for endometriosis. PMID- 2932350 TI - Ovarian surgery in an infertility patient as an indication for a short-interval second-look laparoscopy: a preliminary study. AB - The usefulness of a short-interval second-look laparoscopy (SLL) after ovarian surgery was examined. In 23 infertile women who had either bilateral wedge resection (BWR) of polycystic ovaries, an oophorocystectomy (OC), or resection of endometriomata (RE), adhesions were graded before and after surgery and before and after laparoscopic lysis for each ovary. At SLL, periovarian adhesions involving at least one ovary were observed in all women. Of the 22 women who wanted to become pregnant, 3 of 3 with BWR, 1 of 3 with OC, and 6 of 16 with RE conceived. In the women with residual adhesive disease in both or the only remaining adnexa after SLL, there were no pregnancies; whereas 67% of the women with at least one adnexa free of disease became pregnant (P = 0.005). This preliminary study indicates that ovarian surgery does result in significant adhesion formation and that SLL offers an opportunity to reassess the pelvis, to lyse adhesions, and to establish a postoperative prognosis. PMID- 2932351 TI - Beta-endorphin and met-enkephalin in peritoneal and ovarian follicular fluids of fertile and postmenopausal women. AB - Immunoreactive (IR) beta-endorphin (beta-EP) and met-enkephalin (MET-ENK) have been found in peritoneal fluid (PF) and ovarian follicular fluid (FF). Gel chromatography also revealed the presence of coeluting IR beta-lipotropin and gamma-lipotropin. IR beta-EP and IR MET-ENK levels in healthy menstruating women were from 10 to 40 times higher than those present in circulating plasma, which indicated a possible local production. The highest concentrations of IR beta-EP in FF were found in the largest follicles, whereas in the PF they correlated with the luteal period of the menstrual cycle and with progesterone concentrations. No relevant changes in IR MET-ENK were detected in the FF or in the PF in relation to the phase of the menstrual cycle. In postmenopausal women, the concentrations of the two IR opioid peptides were undetectable in both fluids. PMID- 2932352 TI - Laparoscopy for in vitro fertilization: end of an era. PMID- 2932353 TI - [Effect of L-thyroxine on skeletal muscle fibers of the frog]. AB - L-thyroxin prevents neither the postdenervation decrease of resting MP, nor the increase of input resistance, nor the extrajunctional sensitivity to acetylcholine, but after the injection the cross-sectional areas of muscle fibers decrease more rapidly than after a mere denervation and muscle fibers of new type by myosin-ATPase activity do not appear. The same doses of hormone do not affect properties of muscle fiber membrane but increase the input resistance of membrane and decrease cross-sectional areas of muscle fibers. l-thyroxin seems unable to prevent the appearance of the postdenervation changes in skeletal muscle fibers in adult frog and does not take part in regulation of its differentiation. PMID- 2932354 TI - Properties of ATPase activity in intact vegetative cells and sporulating cells of yeast Saccharomyces cerevisiae. AB - The properties of ATPase activity were examined in the intact cells of yeast. The activity was stimulated by Mg2+, Mn2+ and Co2+. The activity was inhibited by NaN3 and by high concentrations of NaF, NaVO3 and PCMB. Optimal pH for the activity was approximately 8. The maximum value of the activity was obtained in the cells at the early stationary phase and it decreased in 3 hr after transfer to sporulation medium. PMID- 2932355 TI - Effect of phospholipase A2 on Ca2+-stimulated adenosine triphosphatase activity in microsomal fraction of rat submandibular gland. AB - The effect of phospholipase A2 on the Ca2+-ATPase (EC 3.6.1.3) activity in the microsomal fraction of rat submandibular gland was kinetically studied in vitro. The Ca2+-ATPase activity was significantly increased by the treatment with phospholipase A2 in the presence of bovine serum albumin as a scavenger for hydrolyzed products. When the microsomal fraction was incubated with phospholipase A2 in the absence of bovine serum albumin, the Ca2+-ATPase activity was not altered. The Vmax and Km values for both ATP and Ca2+ were increased by the phospholipase A2 treatment, respectively. These results indicated that the activation of Ca2+-ATPase by the phospholipase A2 treatment is due to the increase of Vmax. PMID- 2932356 TI - 12-O-Tetradecanoylphorbol-13-acetate enhances glycolysis in rat thymocytes. AB - The potent tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) induced a rapid increase in glycolysis in rat thymocytes. The increase in the glycolytic flux was also reflected by elevated fructose 1,6-diphosphate levels. TPA treatment did not result in an increase of hexokinase, phosphofructokinase or pyruvate kinase when measured in cell homogenates. It is suggested that the early increase in glycolysis in TPA treated lymphocytes may result from TPA-mediated increase in glucose transport. PMID- 2932357 TI - Intramuscular piroxicam, a new dosage form, in the treatment of acute musculoskeletal disorders. AB - Ten investigators in Austria, Belgium, Denmark, Germany and Switzerland participated in an open trial of intramuscular piroxicam involving 135 patients with selected acute sprains, tendinitis or low back pain. The drug was given in the recommended regimen of 40 mg once daily for 2 days and 20 mg once daily thereafter. Statistically significant improvement from baseline in pain was evident within 1 hour of the initial dose, an effect which was enhanced over a 12 hour period and which lasted for 24 hours. After 3 days of intramuscular injections, pain, tenderness, morning stiffness and back elongation were markedly improved. Subsequent treatment with either intramuscular or oral piroxicam further improved these symptoms and most patients recovered their normal physical activity within a week. The drug was well tolerated; twenty-five patients (18.5%) reported side-effects possibly related to piroxicam. Nearly all were mild or moderate in severity with only six resulting in disruption of therapy. Most adverse reactions involved the upper gastrointestinal tract, but there were no reports of gastric bleeding. Except for a few patients with injection site pain, the side-effect profile was similar to that established with the oral dosage form. Toleration was regarded as excellent or good in about 84% of the patients. The results indicate that intramuscular piroxicam can provide rapid and effective therapy with good toleration in the treatment of acute musculoskeletal disorders. PMID- 2932358 TI - Revisions in isotretinoin labeling. PMID- 2932359 TI - Cat scratch disease. Report of a case with hepatic lesions and a brief review of the literature. AB - An unusual case of cat scratch disease with large hepatic defects is presented. We describe a previously healthy 16-yr-old black man presenting with a neck mass, hepatosplenomegaly, and systemic symptoms. Pathology of the neck mass revealed a lymph node with chronic inflammation and focal necrosis. An abnormal computed tomography scan showed large hepatic defects which were confirmed at peritoneoscopy; biopsy specimens are described. Routine and special stains for bacteria and fungi were all negative. Serologic studies were unremarkable but a cat scratch skin test was positive. Follow-up examinations revealed resolution of all findings. Cat scratch disease should be considered in the differential diagnosis of diseases causing lymphadenopathy, systemic symptoms, and hepatic (and splenic) defects. PMID- 2932360 TI - [Thrombin-plasmin system as a regulator of the aggregate state of body colloids]. PMID- 2932361 TI - [Chalone-antichalone system in hematopoietic disorders]. PMID- 2932362 TI - [Immunological analysis of the content of erythrocyte chalone factors in the blood in certain types of pathology]. PMID- 2932363 TI - Gamma-vinyl GABA. PMID- 2932364 TI - Amplification by glycine of the anticonvulsant effect of THPO, a GABA uptake inhibitor. AB - THPO, a GABA uptake inhibitor, when given in doses of up to 4 mmol/kg (i.p.) to mice, had only a marginal protective effect against seizures induced 1 hr later by 3-mercaptopropionic acid (MPA). THPO (4 mmol/kg), when given in combination with 10 mmol/kg of glycine, protected 60% of the mice from MPA-induced convulsions. The combination of THPO and glycine delayed the onset of metrazol induced clonic convulsions and protected 30% of the animals from seizures, although neither glycine or THPO alone had a significant anticonvulsant effect against metrazol induced seizures. In agreement with earlier findings, the results presented in this work seem to indicate that the synergistic anticonvulsant effects of glycine and GABAergic agents are independent of their mode of action: the effects of GABA agonists (muscimol) GABA-T inhibitors (vinylGABA), or an inhibitor of glial GABA uptake (THPO) are similarly amplified by glycine. PMID- 2932365 TI - Occurrence of beta-endorphin-like immunoreactivity in the brain of the teleost, Boops boops. AB - By immunocytochemical methods the present study describes beta-endorphin-like immunoreactive substance in the brain of Boops boops. Beta-Endorphin-like neurons and fibers were detected in both dorsal and ventral components of the preoptic nucleus and in the nucleus lateralis tuberis. This localization has been discussed in relation to the presence, in the same area, of a well-defined neurosecretory system involved in hypophysial regulation. A beta-endorphin-like immunoreaction was also detected in the Purkinje cells and in processes within the cerebellum molecular layer. Although this last finding remains enigmatic it may suggest a neuromodulatory activity for cerebellum beta-endorphin-like substance. No immunoreaction was observed when the specific antiserum was absorbed with corresponding antigen and with beta-LPH. These tests led to the conclusion that the immunostaining reaction might correspond to a beta-endorphin- or lipotropin-like reaction. Further, the present results show the phylogenetic antiquity of a beta-endorphinergic or lipotropinergic system in the brain, with a stable evolutionary history as a hypophysial regulatory factor or neuromodulatory agent. PMID- 2932366 TI - Genetics of the Lp lipoprotein in Japanese-Americans. AB - Segregation analysis of four Lp assays on 557 children in 227 families reveals a dominant major gene and a residual heritable component that may reflect one or more alleles of weaker effect. Close or moderate linkage to esterase-D (ESD) is excluded. PMID- 2932367 TI - False-positive reporting of Down syndrome on Ohio and New York birth certificates. AB - Although correction for underreporting of congenital malformations on birth certificates is included in most studies, inaccuracy of reporting has not been widely examined. Two separate investigations were conducted on the inaccuracy of Down syndrome (DS) reporting on birth certificates; ie, false-positive cases in which an individual coded as DS did not in fact have DS. In Ohio, 824 individuals were coded as DS on their birth certificate during 1970-1981. Of these, a definitive determination as to whether or not they had DS was made on 778 by using cytogenetic data, medical records, the state's birth defects registry, school records, and by questioning physicians. Fifty-seven false-positives were found, indicating a 7.8% level of coding inaccuracy for all races and 6.9% for whites only. Nine of these arose from miscodings during data processing; 48 were misdiagnosed as DS. This can be contrasted with false-negatives also studied in Ohio, where 66.1% of DS cases were not reported on the birth certificate. No statistical differences were observed between false-positives and true DS in the distribution of sexes, in population size of county of birth, or in year of birth (although there was a declining false-positive rate over the 12 year period). The percentage of DS false-positives, however, was significantly higher for younger maternal ages (greater than or equal to 30 years) than older ones (greater than or equal to 30 years) and for nonwhites compared to whites. Further, there was a strong negative correlation between the percentage of false-positives and the degree of certainty expressed in reporting DS on the birth certificate. PMID- 2932368 TI - [Medical genetics study of the population of Kostroma Province. II. The diversity of hereditary pathology in 5 districts of the province]. AB - The diversity of hereditary pathology in 5 regions of Kostroma district was studied. 32 nosological forms of autosomal dominant, 30 autosomal recessive and 7 X-linked recessive disorders were found. The most frequent autosomal dominant disorders were: neurofibromatosis, pigmentary degeneration of retina, hypochondroplasia, ichtiosis, idiopathic scoliosis. The most frequent among the autosomal recessive disorders were: oligophrenia, pigmentary degeneration of retina, muscular atrophy of juvenile Kugelberg--Welander type, congenital cataract. The most frequent X-linked disorders were: muscular Duchenne type dystrophy and hemophilia A. Analysis of mutant gene distribution over the territory by the study of birthplaces of probands and their parents was carried out. PMID- 2932369 TI - Endpoint distribution for deletions into imm lambda region forming p lambda CM replicons: phage lambda gene rex affects plasmid establishment. AB - For the p lambda CM family of lambda-derived self-encapsidating plasmids, the rexB gene product facilitates plasmid establishment following injection into a new host cell. Temperature-stable chloramphenicol resistance (CmR at 40 degrees C) conferred by low-multiplicity infection with lambda::Tn9 cI857 lysates (Tn9 sites tested: 22.60 or 24.08 kb, in the b region, or 28.41 kb, in int) is usually due to a lambda::Tn9 plasmid (p lambda CM) formed by a deletion penetrating the lambda immunity region. These grow either as plasmids in the absence of, or lytic phages in the presence of N function supplied by a host such as lambda cI857 delta H1 lysogen MS1449. The 'groplaque' (plaque-shaped growth spot) assay, which selects for CmR growth in an MS1449 lawn at 32 degrees C after an initial plaquing period at 37 degrees C, reveals two distinguishable classes of p lambda CM isolates. All variants whose deletions extend into or beyond rexB give rise to visible CmR growth only after the temperature shift to 32 degrees C, and thus produce a hollow-centered 'donut' type of groplaque. In contrast, 16 out of 17 variants whose deletions fall short of rexB produce 'solid' groplaques which appear before the temperature shift. Tests of T4rII phage exclusion show the exceptional 17th variant to be Rex-, confirming the identification of rex as the lambda component whose loss results in the 'donut' groplaque morphology. More specific physiological tests showed that in the absence of Rex the establishment of a newly injected p lambda CM plasmid becomes temperature-sensitive (ts), while plasmid maintenance remains unaffected. This indicates that the role of Rex in plasmid survival is confined to the early stages of transduction, where it might either assist plasmid replication or retard host replication, to help the plasmid replicon achieve a copy number sufficient for stable transmission. PMID- 2932370 TI - Nucleotide sequence of the GDH gene coding for the NADP-specific glutamate dehydrogenase of Saccharomyces cerevisiae. AB - The isolation of the Saccharomyces cerevisiae gene for NADP-dependent glutamate dehydrogenase (NADP-GDH) by cross hybridization to the Neurospora crassa am gene, known to encode for NADP-GDH is described. Two DNA fragments selected from a yeast genomic library in phage lambda gt11 were shown by restriction analysis to share 2.5 kb of common sequence. A yeast shuttle vector (CV13) carrying either to the cloned fragments complements the gdh- strain of S. cerevisiae and directs substantial overproduction of NADP-GDH. One of the cloned fragments was sequenced, and the deduced amino acid (aa) sequence of the yeast NADP-GDH is 64% homologous to N. crassa, 51% to Escherichia coli and 24% to bovine NADP-GDHs. PMID- 2932372 TI - [Occupational and medical rehabilitation problems in chronic manganese poisoning]. PMID- 2932371 TI - [Industrial hygiene problems in salt mining (lakes and ponds)]. PMID- 2932373 TI - [Bacterial contamination of the atmosphere in deep potassium mines]. PMID- 2932374 TI - [Physiological and hygienic characteristics of the start-up period in modern chemical manufacturing]. PMID- 2932375 TI - Characteristics of male fallow deer muscle at a time of sex-related muscle growth. AB - Muscle characteristics of male fallow deer undergoing neck muscle enlargement as the mating season (rut) approached were studied. Five commercially-raised males were slaughtered prerut and five were slaughtered 11 weeks later, just before the rut began. During this period, increases in individual muscle weight were not the same: two of the three neck muscles studied grew more rapidly than the average, whereas the back and two hind leg muscles grew more slowly. The splenius, the neck muscle that grew the most apparently in response to a rise in plasma testosterone, was studied. Cryosections were cut and stained for myofibrillar ATPase so that the muscle fiber classes--slow oxidative (type I), fast oxidative glycolytic (type IIA) and fast glycolytic (type IIB)--could be distinguished. The IIB class was absent from the splenius and the occurrence of I and IIA fibers did not change during the period of splenius growth. However, the splenius of fallow deer increased in activity of NADH-tetrazolium oxidoreductase at the fiber peripheries as the rut approached. Further, fiber areas increased markedly during the period of growth, with type I fibers doubling in area and type IIA nearly trebling. Thus, the endocrinal and/or neural changes associated with the rut differentially affected these fiber types, and since type IIA fibers outnumbered type I by nearly 2 to 1, muscle enlargement is clearly dominated by the former class. Fiber areas were normally distributed for both fiber types, prerut and at the start of the rut, and coefficients of variation were similar. These results suggest that all fibers within a type are equally liable to grow during the growth period. PMID- 2932376 TI - Aids to bridge the communication barrier. PMID- 2932377 TI - [Pulsed Doppler procedure. Noninvasive flow measurements of the fetoplacental unit]. PMID- 2932378 TI - [Hepatitis B--also a partner infection]. PMID- 2932379 TI - [Effects of electroacupuncture on beta-endorphin contents in rats]. AB - Effects of electroacupuncture (EA) on pain threshold and beta-endorphin (beta End) contents in plasma, pituitary (Pit), hypothalamus (Hyp) and cerebrospinal fluid (CSF) were studied in nontreated, dexamethasone (Dex) treated and adrenalectomized (Adrex) male SD rats by the use of specific determination of rat beta-End (combination of HPLC and RIA). EA increased pain threshold and plasma beta-End with no effect on beta-End contents in Pit, Hyp and CSF. Dex did not affect control pain threshold, but tended to reduce EA-induced increase in pain threshold (EA-analgesia, EAA) and EA-induced increase in plasma beta-End. Adrex increased plasma beta-End without change in control pain threshold. Adrex tended to reduce EAA, but a tendency of further increase in plasma beta-End was observed after addition of EA. Adrex increased Pit beta-End, but no further change in Pit beta-End was observed after addition of EA. A positive correlation between plasma beta-End and plasma ACTH was observed in nontreated, Dex treated and Adrex rats. No correlation between plasma beta-End and potency of EAA was observed in nontreated, Dex treated and Adrex rats. The hind-paw pressure test without EA increased plasma beta-End to the same degree as that produced by EA, and it produced no analgesia. These results suggest that Pit beta-End may not be mainly involved in the development of EAA. PMID- 2932380 TI - Hepatitis A and B in non-institutionalized mentally retarded patients. AB - The high incidence of hepatitis A and B in institutionalized patients with Down's syndrome is not fully understood. Under poor hygienic conditions immunological alterations might predispose to these infections. To minimize environmental influences, 125 patients with Down's syndrome (mean age 11.9 years) living at home with their families were studied for the occurrence of serological markers of Hepatitis A and B. 106 outpatients with mental retardation of other genesis (mean age 12.4 years), and 114 consecutive voluntary blood donors (mean age 18.0 years) from the same area served as controls. Evidence of previous hepatitis A virus infection was found in 5.6% of Down's patients, in 9.4% of other mentally retarded patients, and in 16.7% of healthy controls. Evidence of previous or ongoing hepatitis B virus infection was a common finding in both groups of mental retardation (Down's syndrome 20.0%, other mentally retarded patients 11.3%) in sharp contrast to healthy blood donors (0.9%, p less than 0.05). Patients with Down's syndrome, however, revealed a much higher incidence of HBs-antigenemia as compared with other mentally retarded patients (12.8% vs. 2.8%, p less than 0.01). All HBs antigen-positive cases had normal transaminase levels and no overt clinical signs of liver disease, suggesting an asymptomatic carrier state. These data indicate that hepatitis A is not a special risk for mentally retarded outpatients, while hepatitis B virus infection is hyperendemic even in not institutionalized patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2932381 TI - A comparison between mean frequency estimators for multigated Doppler systems with serial signal processing. PMID- 2932382 TI - In vivo modulation of rat complement activities by infusion of anti-H antibodies. AB - Regulation of the activity of the alternative pathway of complement occurs by the plasma proteins I and H. H is able not only to prevent formation of the amplification convertase C3bBb but also to cause the decay-dissociation of Bb from C3bBb. The present studies have investigated the role of H in vivo. Affinity purified goat (Fab')2-anti H was infused intravenously in rats, and its effect on C4, C3 and CH50 activities was assessed. In addition, H, C3, C4 and B were quantitated by immunochemical methods. H depletion was dependent on the dose of anti-H, and maximal consumption in vivo occurred between 5 and 15 min. A maximum of 51% and 77% hemolytic C3-consumption was seen after 15 min with 3.8 and 8.4 mg anti-H, respectively. The injection of 6.3 mg affinity-purified goat IgG anti-rat H caused 96.8 +/- 0.7% and 85.0 +/- 1.4% consumption of CH50 and C3 hemolytic activity, respectively. Using this dose of IgG anti-rat H, it was found that the clearance in rats of rat erythrocytes sensitized with 8000 molecules of guinea pig IgG2 per E was impaired as compared to the clearance of these intermediates in control rats injected with a comparable dose of normal goat IgG. The results indicate that H functions as a potent regulator of C in vivo and that infusion of anti-H can be used as a method to achieve depletion of circulating complement components. PMID- 2932383 TI - Effect of Bacillus Calmette-Guerin on the in vitro generation of cytotoxic T lymphocytes. II. Role of interleukin-1-like factors and of soluble suppressor factors. AB - The injection of BCG vaccine in C57BL/6J mice results in the suppression of the generation of cytotoxic T lymphocytes (CTL) in mixed lymphocyte cultures (MLC) and of mitogenic reactions to concanavalin A (Con A). Suppression is mediated by macrophage-like suppressor cells. Since previous work had indicated that suppression involved the inhibition of the production of interleukin-2 (IL-2), the effects of BCG on interleukin-1 (IL-1), a monokine required for IL-2 production, were investigated. It was found that the release of IL-1-like activity in spleen cell cultures stimulated with LPS or Con A was increased by previous BCG treatment of the cell donors. In MLC, the release of IL-1-like activity was also increased by BCG. However, the detection of IL-1-like activity in MLC supernatants was prevented by the presence of a suppressor factor. In this case, the IL-1-like activity could be separated with gel filtration from the suppressor factor which had higher molecular weight. The production of IL-1-like activity by CBA/J spleen cells, which are not suppressed by BCG, was not significantly different from that of C57BL/6J cells, which are markedly suppressed. Moreover, the addition of IL-1 to the BCG-suppressed cultures not only did not restore normal reactivity, but actually further suppressed CTL formation. It was concluded that BCG-induced suppression cannot be attributed to decreased IL-1 activity. The suppressor factor discovered during these investigations may have a role in this type of suppression. PMID- 2932384 TI - The role of antigen recognition and suppressor cells in mice with oral tolerance to ovalbumin. AB - The induction of tolerance by feeding proteins may prevent potentially harmful delayed-type hypersensitivity (DTH) reactions to food antigens. Suppressor T cells (Ts) are present in mice with tolerance of systemic DTH after feeding ovalbumin (OVA) but, as other immunoregulatory mechanisms have also been described, the exact role of Ts in maintaining tolerance is not known. In this study, we have used the ability of native and denaturated OVA to cross-react at the level of helper/effector T cells, but not Ts, to re-examine the role of Ts in oral tolerance to OVA. Mice immunized with native OVA (nOVA) or denatured OVA (dOVA) in adjuvant had fully cross-reacting DTH to either nOVA or dOVA, but intravenous administration of antigen induced Ts which were specific for the appropriate form. Mice fed nOVA or dOVA had identical tolerance of systemic DTH to both forms of OVA, and feeding nOVA induced splenic Ts which suppressed the DTH response to both nOVA and dOVA. Splenic Ts could not be detected in mice fed dOVA. The results support the hypothesis that tolerance of systemic DTH in mice fed native proteins is due to Ts. Although, for the moment, there is no complementary evidence for a role for Ts in oral tolerance to denatured proteins, this study is consistent with the idea that Ts are the mechanism which normally prevent enteropathy due to DTH against dietary proteins. In addition, our study underlines the differences between orally and parenterally induced Ts and reinforces the view that fed proteins induce Ts after processing by the gut or its lymphoid accessory cells. PMID- 2932385 TI - Suppression of induced erythrocyte autoantibodies is dependent on Lyt 1 cells. AB - When normal mice are immunized with rat RBC, autoantibodies to mouse red cells and antigen-specific suppressor cells are generated. Suppressor cell activity is found in T-enriched populations and suppresses only the induction of autoantibody, not ongoing or secondary autoantibody responses. Using antibodies lytic for either B cells or distinct T-cell subpopulations, we are able to show that suppression is dependent on the presence of Lyt 1+ T cells. PMID- 2932387 TI - Gamma-ray induced ageing mutants of Neurospora crassa: response to some antioxidants and chloramphenicol. PMID- 2932386 TI - Glucocorticoids inhibit IgE receptor expression on the human monocyte cell line U937. AB - Cells of a human monocyte-like cell line (U937) were analysed for IgE Fc receptors (Fc epsilon R) before and after glucocorticoid treatment. Specific binding of human myeloma IgE (Sha) was measured by 125I-labelled IgE, and by fluorescein-labelled IgE monitored by flow cytometry. Treatment of cells with dexamethasone or other steroids with glucocorticoid activity caused a significant decrease in Fc epsilon R expression. The inhibition was dose dependent, with a half-maximal effect at 20 nM dexamethasone, a concentration which is near to the dissociation constant of glucocorticoid receptors for dexamethasone. Inhibition of Fc epsilon R was significant beginning 8 h following glucocorticoid treatment and reached a plateau at 24 hr. The Ka for IgE binding was similar for control and dexamethasone-treated cells, while the number of IgE binding sites was decreased by 50-60%. Culture supernatants from dexamethasone-treated U937 cells which were concentrated 10-fold and depleted of free steroid did not affect Fc epsilon R expression. These results demonstrate that glucocorticoids can directly decrease the number of Fc epsilon R. This effect could participate in the glucocorticoid-induced suppression of IgE-mediated allergic reactions. PMID- 2932388 TI - Effect of morphine on acetylcholinesterase & adenosine triphosphatase activities in rat tissues. PMID- 2932390 TI - Candida albicans and Candida stellatoidea, in contrast to other Candida species, bind iC3b and C3d but not C3b. AB - It was demonstrated that complement-coated sheep erythrocytes bind to Candida albicans cells grown in serum-free RPMI 1640 medium. Testing of purified complement components proved that iC3b and C3d were responsible for the reaction, whereas C3b and C3b-H reacted only slightly if at all. Binding occurred only to C. albicans and C. stellatoidea, not to other species pathogenic to humans. There was evidence of a lectinlike nature of the effect. PMID- 2932391 TI - Factors affecting cure of visible light activated composites. AB - Since visible light activated composites first appeared in 1978 they have become internationally popular for the aesthetic restoration of anterior teeth. With an ever increasing number of composite formulations and curing lights available and as yet no widely recognized standard for measuring depth of cure, it is difficult to interpret claims being made by manufacturers. A laboratory technique using incremental measurement of surface hardness has been shown to provide a convenient means of assessing cure throughout the depth of a composite sample, which relates to the clinical situation. Using this method it is possible to demonstrate that physical and chemical formulation factors; the nature of the light source; and the control exercised by the practitioner, are all important in determining the quality of cure achieved and hence likely long term performance of the restoration. Light cured composites are now being more widely used in the restoration of occlusal cavities in posterior teeth, where the technique offers advantages of control, handleability and a lack of porosity unattainable in a chemically cured system. In large Class II cavities depths can exceed 7 mm, and in an application where performance is critical it is essential that a satisfactory level of cure is achieved. To obtain this, even with exposure times significantly longer than those currently being recommended, it is advisable to employ a layering technique for any cavity greater than 3 or 4 mm in depth. PMID- 2932389 TI - The ability of Salmonella typhimurium to produce the siderophore enterobactin is not a virulence factor in mouse typhoid. AB - One of the nonspecific defense mechanisms of higher animals is their ability to limit iron availability to infecting bacteria. Thus it has been argued that all pathogenic bacteria must have special mechanisms to obtain iron in the host environment. Salmonella typhimurium is known to produce a siderophore, enterobactin, with which it can obtain iron from host transferrin. Previous studies have indicated that the production of this molecule is necessary for the ability of intraperitoneally injected. S. typhimurium cells to cause mouse typhoid, a largely intracellular infection. We have reexamined this finding with wild-type S. typhimurium and isogenic strains carrying the nonenterobactin producing mutation ent-1 or ent-7. Our findings demonstrate that, although enterobactin production is necessary for growth in normal mouse serum, it does not affect the ability of S. typhimurium to cause mouse typhoid. Based on these findings and published results of other investigators on the role of siderophores in intracellular pathogens, a more comprehensive investigation of the importance of siderophores in intracellular infections may be warranted. PMID- 2932392 TI - Lymphocyte subsets in infants: relationships to feeding, atopy, atopic heredity and infections. AB - Numbers of T and B lymphocytes and T cell subsets were measured longitudinally in blood samples of 68 healthy infants from 1 month to 28 months of age. Monoclonal antibodies against cell surface antigens (OKT3, OKT4, OKT8, and OKIal) and antibodies to immunoglobulin heavy chains (gamma, mu, alpha and delta) were used for immunofluorescent staining. The absolute number of T lymphocytes (OKT3) was found to be highest at the age of 6-7 months, reflecting the greater numbers of both helper (OKT4) and suppressor (OKT8) cells. The percentages of OKT4 and OKT8 positive cells and hence the ratios of these cells were very stable throughout the study period. Relatively, breast-fed infants had more suppressor (OKT8) cells than infants on formula, but the difference was not apparent in absolute counts. Change to formula feeding caused an increase in B cells. The heredity for atopy did not influence the total numbers of T cells or cell numbers in the different subgroups. At the age of 4 months an altered helper/suppressor ratio was noted in infants who later developed a severe atopy. At the age of 28 months the relative number of T cells was lower in atopic than nonatopic infants. The rate of respiratory infections did not affect these numbers. PMID- 2932393 TI - Lymphocyte transformation induced by autologous cells. XVII. Lower autologous mixed lymphocyte reaction in subjects with a history of hayfever. AB - The autologous mixed lymphocyte reaction (AMLR) is impaired in patients with a number of diseases associated with abnormal immunoregulation. Since allergic disorders are also associated with abnormal immunoregulation, we assessed the AMLR in individuals with a history of ragweed hayfever. Lymphocytes from allergic subjects had a lower AMLR than nonallergic controls by rank order analysis. These results support the association of abnormal in vivo immunoregulation with reduced AMLR. PMID- 2932394 TI - Interventional cardiac catheterization in congenital heart disease. AB - Cardiac catheterization has proved its value as a major tool in the diagnosis of congenital cardiac defects. The advent of non-invasive imaging of various sorts has altered the role of diagnostic catheterization. Within the past two decades cardiac catheter instruments to provide therapy have been applied to many lesions. Improvements in design and methods will expand the use of therapeutic catheterization. It is inevitable that better results will be obtained for those defects currently being treated that way, and that the method will be applied to other conditions. PMID- 2932395 TI - Complex coronary angioplasty: an alternative therapy. PMID- 2932396 TI - Percutaneous transluminal coronary angioplasty in left main stem coronary stenosis: a five-year appraisal. AB - Left main stem coronary stenosis is now uniformly treated with coronary artery bypass grafting. The advent of percutaneous transluminal coronary angioplasty has permitted a non-operative improvement in myocardial blood flow in many cases of single- and multi-vessel coronary atherosclerosis. The use of percutaneous transluminal coronary angioplasty in left main stem coronary stenosis has been sporadic and controversial. Twenty percutaneous transluminal coronary angioplasties were attempted in 19 patients as the treatment of choice for left main stem coronary stenosis in the past 66 months. The primary success rate was 95% (19/20 patients). The emergency surgery was performed only once (5%), and no death occurred secondary to percutaneous transluminal coronary angioplasty itself. In the follow-up (mean 41 months) period, 12 patients (63%) remained in satisfactory condition with no further need for surgical intervention. Seven patients (37%) ultimately required coronary artery bypass grafting. Although coronary artery bypass grafting will remain the fundamental treatment for left main stem coronary stenosis, this series delineates those anatomic and clinical exceptions wherein percutaneous transluminal coronary angioplasty may be utilized as the primary therapy for left main stem coronary stenosis. PMID- 2932397 TI - Atrioventricular septal defect with a well developed primary component of the atrial septum ("septum primum"). AB - A heart is described with an atrioventricular septal defect in which the lower part of the atrial septum ("septum primum") was well developed and in which superior and inferior bridging leaflets were attached neither to the crest of the ventricular septum nor the inferior rim of the atrial septum. Diagnostic pre operative angiographic and echocardiographic features and the method of surgical correction are outlined. PMID- 2932398 TI - A comparison of information obtained by ultrasound examination and cardiac catheterisation in paediatric patients with congenital heart disease. AB - Fifty-eight paediatric patients were studied by cross-sectional echocardiography and pulsed Doppler ultrasound in a blind fashion. The information obtained was compared with data collected at cardiac catheterisation. The correct anatomical diagnosis was made by ultrasound in almost all cases but in 11 patients the diagnosis was incomplete or incorrect. Flow measurements made at the tricuspid valve, the pulmonary trunk and the ascending aorta using pulsed Doppler ultrasound correlated well with Fick measurements (r greater than 0.9 at all three sites). The correlation of pressure gradients by the two methods was 0.94. Measurement of the time to peak velocity in the pulmonary trunk provided a method for the identification of patients with elevated pulmonary pressure but the relationship with measured pressures was not sufficiently strong to provide a high degree of reliability. PMID- 2932400 TI - Monitoring of nonsteroidal antiinflammatory drugs. AB - Until now, little or no attention has been paid to the monitoring of therapy with nonsteroidal antiinflammatory drugs (NSAIDs). The authors discuss reasons for that situation. They emphasize that lack of monitoring of unwanted side-effects of the widely used NSAIDs is no doubt due to the overuse of these drugs. The expedience and a protocol concerning the efficacy and toxicity monitoring of such drugs are critically discussed. The authors stress that toxicity monitoring should be performed in selected patient groups that to only in those patients at risk. PMID- 2932399 TI - Injectable gold dermatitis and proteinuria: retreatment with auranofin. AB - Seven female patients with classical rheumatoid arthritis (RA), treated successfully with injectable gold salts (Fosfocrisolo ICI, 0.10 g/week, with a serum gold concentration of 200-400 mcg/dl), experienced severe gold side-effects after 3 to 20 months of therapy, requiring their withdrawal from gold despite the good results in both clinical and laboratory findings. Four patients showed mucocutaneous side-effects (2 dermatitis and 2 stomatitis) and three a moderate or severe proteinuria. Renal biopsy was performed in these patients, with a histological picture of membranous glomerulonephritis referable to gold therapy. Remission inducing drug (R.I.D.) therapy being mandatory in patients with a chronic progressive disease, and in view of the previous efficacy of gold salts, the patients were put on oral gold, Auranofin being administered 3 mg b.i.d. Both the mucocutaneous side-effects and the proteinuria ameliorated within 2 to 6 months, and the remission of the disease was maintained. The chemical and pharmacokinetic differences between the above two gold compounds are discussed. PMID- 2932402 TI - Rosacea: a reply to Wilkin's reply. PMID- 2932401 TI - Pustular acne. AB - Pustules from 92 new cases of pustular acne and gram-negative folliculitis were cultured in aerobic medium for superimposed bacterial infection. During the treatment of 1,561 new patients with papular acne with tetracycline and topical clindamycin and antibacterial soaps, an additional 10 developed pustules. The majority showed in vitro resistance to ampicillin. The effective treatment was co trimoxazole and topical gentamicin. A new classification of acne with practical therapeutic use is needed. PMID- 2932403 TI - Exfoliative dermatitis following intravesical therapy with mitomycin C. PMID- 2932404 TI - Audiological findings in Down's children. AB - The authors have investigated the auditory function in 35 Down's subjects, aged between 1 month and 16 years. Clinical examination revealed the occurrence of impaired nasal breathing in 18 subjects (51.4%), while otoscopy results were bilaterally normal in 12 cases (34.3%). Behavioural pure-tone audiometry yielded reliable results in 10 children (28.6%), impedance tests in 28 (80.0%), and brainstem audiometry in 29 (82.9%). A clinical and audiological follow-up has been performed in 11 cases (31.4%). Pure-tone audiometry, which may be employed in all cases only beyond 8 years of age, revealed a conductive hearing loss in 7 cases (20.0%). Impedance tests, whose usefulness is limited by the high occurrence of external ear canal stenosis, showed bilateral type A tympanograms only in 8 cases (28.6%). Stapedial reflex data were often missing, even in presence of a type A tympanogram, due to the weakness of tubaric muscles and to the presence of ossicles abnormalities. ABR has been performed in 29 cases (82.9%) and resulted to be as effective as in the normal population. It revealed a normal configuration concerning threshold and morphology in 16 cases (55.1%). The authors conclude that middle ear pathology in the Down's population is more frequent than expected on clinical basis and that objective tests are mandatory in order to obtain a reliable evaluation. While impedance tests are very sensible in detecting mild middle ear pathologies, but are not effective in threshold definition, brainstem audiometry is the choice tool in the uncooperative child, even if it cannot allow a differential diagnosis between normality and mild low frequency conductive hearing losses. PMID- 2932405 TI - Lymphangioma of the larynx as a cause of progressive dyspnea. AB - The following is a case report of a lymphangioma of the larynx in a 16-year-old girl with Down's Syndrome. The clinical record of the girl, the diagnosis of the tumour and its surgical treatment as well as the postoperative course and the follow-up results are described. PMID- 2932406 TI - The role of platelet-activating factor in experimental immune complex pathology. AB - Tissue localization of immune complexes (IC) after infusion of synthetic platelet activating factor (PAF) in rabbits was studied. Bovine serum albumin (BSA) was injected intravenously either before or after the infusion of synthetic PAF, later followed by the administration of anti-BSA antibodies over a 30-min period. Control rabbits received both BSA and anti-BSA antibodies, followed by lyso-PAF or saline-BSA instead of PAF. The infusion of PAF induced structural alterations in the heart, lung and kidney which were consistent with an increased vascular permeability. Deposits of BSA, IgG, and C3 were found in the heart, lung, and kidney of rabbits infused with PAF but not in control rabbits. In the liver of PAF-infused rabbits, immune deposits were only infrequently observed, whereas they were constantly present in the cardiac valves, thoracic aorta and at the bifurcation of the renal artery as they were in the control rabbits. These results suggest that PAF favors the localization of IC in the heart, lung and kidney vessels but does not influence the formation of immune deposits at the sites of turbulence of the blood flow. PMID- 2932407 TI - Enzyme cytochemistry. PMID- 2932408 TI - Interleukin-2 and aging: decreased interleukin-2 production in healthy older people does not correlate with reduced helper cell numbers or antibody response to influenza vaccine and is not corrected in vitro by thymosin alpha 1. AB - The capacity of lymphocytes obtained from healthy young or old volunteers to produce interleukin-2 was measured and the results were compared with other measures of immune function. The in vitro effect of thymosin alpha 1 on interleukin-2 production was also measured. Interleukin-2 was lower in lymphocytes from the elderly, and individuals with low production also had lower proliferative responses in vitro to phytohemagglutinin. These individuals did not have a reduced helper T-cell number, abnormal ratio of helper to suppressor T cells or reduced antibody production in response to vaccine. Thymosin alpha 1 did not have a consistent effect on interleukin-2 production. PMID- 2932409 TI - Aclacinomycin-A inhibits the development and the expression of suppressor cell activity to contact sensitivity. AB - Aclacinomycin-A, a cytotoxic antibiotic, is capable of inhibiting the development and expression of suppressor cell activity for the contact sensitivity reaction to picryl chloride elicited by two intravenous injections of 3.5 mg picryl sulfonic acid when given as a single dose of 4 mg/kg 2 or 4 days before the first or 1 or 3 days after the second injection of picryl sulfonic acid. This inhibition may occur because aclacinomycin-A inhibits the development and expression of both suppressor T-cells and their precursors. In addition, it is shown that aclacinomycin-A diminishes the capacity of spleen T-cells from picryl sulfonic acid-injected mice to inhibit upon adoptive transfer the contact sensitivity reaction to picryl chloride of normal and presensitized animals. PMID- 2932410 TI - Enhancement of helper and suppressor T cell activities by thymosin alpha 1 injection in old mice. AB - A single injection of immunodeficient old (15-24 month old) BDF1 mice with 1-100 micrograms of synthetic thymosin alpha 1 (T alpha 1), a 28-amino acid residue peptide, shortly before horse erythrocyte (HRBC)-priming, enhances the helper activity of their spleen cells. Helper activity of spleen cells from uninjected or T alpha 1-injected HRBC-primed old mice was titrated by adding graded numbers of these primed cells to cultures containing a constant number of normal spleen cells from unprimed young (3-month-old) mice and the conjugate 2,4,6 trinitrophenyl (TNP)-HRBC. As evaluated from the in vitro anti-TNP antibody response, spleen cells exhibit higher helper activity when derived from T alpha 1 injected, as compared to uninjected, HRBC-primed old mice. No effect is observed when T alpha 1 is injected in young mice before HRBC-priming. Old mice were also injected with the N14 (N-terminal amino acid residues 1-14) or the C14 (C terminal amino acid residues 15-28) synthetic fragments of the T alpha 1 molecule. Injection of T alpha 1 or the N14 fragment restores the helper activity of old mice to levels comparable to that displayed by helper cells from young mice. Conversely, injection of the C14 fragment in old mice induces only a negligible increase in helper activity of their spleen cells. T cells from HRBC primed mice were separated by nylon wool filtration into Th1 (non-adherent) and Th2 (adherent) T cells and these cell subpopulations were assayed for helper activity. Helper activity of Th1 and Th2 cells is found to be impaired by aging when they are tested either separately or upon their recombination.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2932411 TI - Why Huntington's disease isn't unique. PMID- 2932412 TI - Isoenzyme variation in the common shrew (Sorex araneus) in Britain, in relation to karyotype. AB - Samples of common shrews with an Aberdeen race, Oxford race and Hermitage race karyotype and from the Oxford-Hermitage hybrid zone were screened for genotype at six polymorphic enzyme loci. The common allele at all loci was the same in all samples suggesting that the degree of genic divergence between the karyotypic races is not great. However, shrews of the Aberdeen race appear to be somewhat distinct. There were differences in allele frequencies, range of alleles and heterozygosities at the Mpi-1, Pgm-2 and Pgm-3 loci between the Aberdeen race samples and samples of other karyotypic categories. The allele frequency variation across the Oxford-Hermitage hybrid zone is not substantially linked with karyotype frequency change, but there is notable allele frequency variation between close sites of similar habitat, particularly at the Pgm-2 and Pgm-3 loci. This suggests that gene flow between close sites may be reduced sufficiently in some instances to allow allele frequency change by genetic drift. This may have implications for the mode of origin of karyotypic races of common shrew. PMID- 2932413 TI - Allergic contact dermatitis from organophosphorus insecticides. PMID- 2932414 TI - T suppressor lymphocytes reverse ongoing acute allograft rejection. AB - (LEW X BN)F1 cardiac allografts are rejected within 8 days in untreated LEW recipients. At the critical time point of 5 days after transplantation, the obviously rejecting grafts are enlarged and maximally infiltrated by host cells as shown by 111In-labeled lymphocyte tracer studies. However, when such hearts were retransplanted back to naive (LEW X BN)F1 secondary hosts, they survive indefinitely, showing that even late rejection is reversible in the absence of sustained host immunological drive. Attempts were then made to abrogate this advanced immune responsiveness using Cyclosporine (CsA). CsA therapy (15 mg/kg/day for 7 days) starting from day 5 produced indefinite graft survival, similar as if initiated at the time of operation. Addition of exogenous IL-2, which drives the proliferation of Tc, could not reverse this effect. Serial changes in phenotype of lymphocyte subpopulations infiltrating both acutely rejecting and indefinitely functioning cardiac allografts in unmodified and CsA treated hosts, respectively, were then studied. Ratio of Th:Tc/s cells in acutely rejecting grafts was 1.6 by day 3; it inverted abruptly to 0.7 by day 5-6, suggesting predominance of Tc/s during the later stages of allograft rejection. Similarly, treatment with CsA produced a transient depression of Th, with recovery of original Th:Tc/s ratio during the next 2-3 weeks. Adoptive transfer experiments were then performed to investigate the functional significance of these findings.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2932415 TI - Adventure, Etc.--a health-promotion program for chronically ill and disabled youth. AB - Adolescents with a chronic illness or physical disability have a more difficult time separating from parents, achieving a sense of mastery, developing social skills among peers, and achieving a positive body-image than do able-bodied adolescents. To promote attainment of these developmental tasks, Adventure, Etc. was created as a wilderness/urban Outward Bound experience for chronically ill, physically disabled, and able-bodied teens. Pre- and posttesting and interviewing assessed locus of control, self-image, family environment, and family dynamics. Over a two-year period, 37 teens completed the program and were tested; 23 were chronically ill or disabled. The chronically ill/disabled group showed a significant increase in internal locus of control. No change was found in the able-bodied group. Both the able-bodied and the disabled/chronically ill groups showed a significant improvement in body image. Reported family conflict declined, as did family recreational involvement, while individual recreational activities among these adolescents increased. Based on these results, new follow up activities for the parents and adolescents were initiated to further the gains of program participants. PMID- 2932416 TI - Bactericidal activity of ciprofloxacin in serum and urine against Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus and Streptococcus faecalis. AB - Ten volunteers received three doses of 500 mg ciprofloxacin, orally every 12 hours. After the last dose, mean serum levels were (mg/l +/- SD) 2.4 +/- 0.83 at 1 h; 0.91 +/- 0.30 at 4 h and 0.18 +/- 0.04 at 12 h. At 1 h the median serum bactericidal activity was satisfactory only against the Escherichia coli (1:256) and Klebsiella pneumoniae (1:128). In urine collected from 0 to 4 h and 8 to 12 h after the last dose, the mean ciprofloxacin level was respectively 482.5 +/- 324.7 and 80.9 +/- 48.2 mg/l +/- SD. Bactericidal activity in urine was high even against the least susceptible species tested: Pseudomonas aeruginosa, Staphylococcus aureus and Streptococcus faecalis. A post antibiotic effect was demonstrated in 22 out of the 29 strains tested, ranging mainly from 1 to 3 h. Ciprofloxacin 500 mg orally twice a day is a bactericidal regimen against a wide range of urinary pathogens but has a limited systemic activity. PMID- 2932418 TI - Noninvasive Doppler determination of cardiac output during submaximal and peak exercise. AB - We compared pulsed Doppler (PD) measurements of stroke volume (SV) and cardiac output (CO) as a function of work load with previously reported values that were obtained by standard invasive methods. Suprasternal notch measurements of Doppler shifted frequency (delta f) were obtained from the ascending aorta and SV calculated with the Doppler equation and an independent measurement of aortic diameter. Motion artifacts were minimized with the aid of a restraining table cycle ergometer. Signal aliasing was accommodated with manual summation of delta f waveforms. A total of 207 determinations were made in 10 sitting subjects exercising to exhaustion. Linear regression analysis of CO vs. work load was significant (P less than 0.001). The correlation coefficient (r = 0.95) and standard error of estimate value (1.21 1/min) were similar to values from the literature. Absolute values of CO and SV underestimated the literature values across all work loads. Technical reproducibility was assessed by comparing with paired t tests the differences between 65 duplicate serial measurements of CO and SV at rest and exercise. No significant differences (P less than 0.001) were found. We concluded that PD-determined SV and CO are reproducible and correlate linearly with work load in a manner consistent with reported invasive techniques. Thus the PD method appears suitable for use during submaximal and peak exercise. PMID- 2932417 TI - Binding of the glycopeptide antibiotic teicoplanin to D-alanyl-D-alanine-agarose: the effect of micellar aggregates. AB - Teicoplanin, as well as the other antibiotics of the vancomycin group, was shown to bind specifically to D-alanyl-D-alanine-agarose (D-Ala-D-Ala-AGA) (A. Corti and G. Cassani, Appl. Biochem. Biotechnol. 11, 101-110 (1985)). This finding is extended, showing that the binding is as a function of concentration and physical form of the antibiotic in solution, i.e., monomers or micellar aggregates. At concentrations below the critical micelle concentration (CMC) teicoplanin binds with an affinity and a capacity similar to the other antibiotics of the same group such as vancomycin and ristocetin A. At concentrations above the CMC three times more teicoplanin is bound to D-Ala-D-Ala-AGA than the other two antibiotics. Equilibrium binding experiments carried out at different pHs with teicoplanin in the monomeric or micellar form indicate that the excess binding of teicoplanin occurs in the presence of micelles. Elaboration of binding data according to Scatchard indicates that the maximum binding capacity of the resin is increased 3.6 times when teicoplanin is in the micellar form. On the contrary, the apparent binding affinity is lower. PMID- 2932419 TI - Effect of swimming training on cardiac function and myosin ATPase activity in SHR. AB - Male spontaneously hypertensive rats (SHR) and Wistar-Kyoto normotensive rats (WKY) were subjected to swimming training 6 times/wk, commencing at 4 wk of age, to determine whether this type of endurance exercise might alter contractile proteins and cardiac function in young adult SHR. The total duration of exercise was 190 h. Myofibrillar adenosinetriphosphatase (ATPase) activity was assayed at various free [Ca2+] ranging from 10(-7) to 10(-5) M. Ca2+-stimulated ATPase activity of actomyosin and purified myosin was determined at various Ca2+ concentrations both in the low and high ionic strength buffers. Actin-activated myosin ATPase activity of purified myosin was assayed at several concentrations of actin purified from rabbit skeletal muscle. Under all these conditions the contractile protein ATPase activity was comparable between trained and untrained WKY and SHR. Analysis of myosin isoenzymes on pyrophosphate gels showed a single band corresponding to V1 isoenzyme, and there were no differences between swimming-trained and nontrained WKY and SHR. Ventricular performance was assessed by measuring cardiac output and stroke volume after rapid intravenous volume overloading. Both cardiac index and stroke index were comparable in nontrained WKY and SHR but were significantly increased in the trained groups compared with their respective nontrained controls. These results suggest that myosin ATPase activity and distribution of myosin isoenzymes are not altered in the moderately hypertrophied left ventricle whether the hypertrophy is due to genetic hypertension (SHR) or to exercise training (trained WKY). Moreover, the data indicate that SHR, despite the persistence of a pressure overload, undergo similar increases in left ventricular mass and peak cardiac index after training, as do normotensive WKY. PMID- 2932420 TI - Headache at high altitude is not related to internal carotid arterial blood velocity. AB - The cause of headache in persons going to high altitude is unknown. Relatively severe hypoxemia in susceptible subjects could induce large increases in cerebral blood flow that then could initiate the headache. Thus we measured noninvasively, by Doppler ultrasound, changes in internal carotid arterial blood velocity (velocity) in 12 subjects in Denver (1,600 m) and repeatedly up to 7 h at a simulated altitude of 4,800 m (barometric pressure = 430 Torr). Six subjects, selected because of prior history of high-altitude headache, developed comparatively severe headache at 4,800 m, and four subjects, without such history, remained well. Two subjects developed moderate headache. Velocity at 4,800 m did not correlate with symptom development, arterial O2 saturation, or end-tidal PCO2. Also, neither velocity nor blood pressure was consistently elevated above the Denver base-line values. During measurements of hypercapnic ventilatory response in Denver, velocity increased linearly with end-tidal PCO2, confirming that our Doppler method could demonstrate an increase. Also, 30 min of isocapnic or poikilocapnic hypoxia caused small increases in velocity (+8 and +6%) during the base-line measurement at low altitude. Although even a small increase in cerebral perfusion could contribute to headache symptoms at high altitude, cerebral blood flow does not appear to play a primary role. PMID- 2932421 TI - AHEC and family practice. PMID- 2932422 TI - Pneumatic anti-shock garment. Risks and rewards. PMID- 2932423 TI - Three-wheelers--unsafe? PMID- 2932424 TI - Training for public health professionals: diagnosis and cure. PMID- 2932425 TI - Deoxynivalenol in hard red winter wheat: relationship between toxin levels and factors that could be used in grading. AB - A study was made of deoxynivalenol (DON) incidences and levels in 1982 hard red winter (HRW) wheat grown in areas of Nebraska and Kansas known to have scabby wheat. Samples of wheat harvested in the areas were collected from elevators and analyzed for DON by gas chromatography with an electron capture detector. Of the 161 samples analyzed, 42% contained less than or equal to 1 ppm; 68% contained less than or equal to 2 ppm; 90% contained less than or equal to 4 ppm. There were differences in the occurrence of DON in the 5 areas identified in eastern Nebraska and Kansas. The mean level of DON decreased from north to south in these areas in the following order: 2.81, 2.73, 2.05, 1.52, and 0.83 ppm. An area in north central Kansas had a mean level of DON of 0.50 ppm. Correlations were made between DON incidences and levels in HRW wheat and factors used in grading wheat. The occurrence of DON was highly correlated with percent total kernels damaged by mold, percent total defects, and percent total scab damage. PMID- 2932426 TI - Liquid chromatographic determination of alpha-zearalenol and zearalenone in corn: collaborative study. AB - The liquid chromatographic determination of alpha-zearalenol and zearalenone in corn was collaboratively studied. Each of 13 collaborators received 7 corn samples; 2 were blanks and 5 were spiked to contain 50, 100, and 200 ng alpha zearalenol/g and 50, 100, 500, 1000, and 4000 ng zearalenone/g. Four sets (including blanks) of blind duplicates were included in the study. Five naturally contaminated corn samples (one in duplicate) were also provided. All collaborators detected both mycotoxins at 50 ng/g. Average recoveries reported by all collaborators ranged from 81.9% at 200 ng/g to 100.3% at 50 ng/g for alpha zearalenol and from 77.8% at 1000 ng/g to 123% at 50 ng/g for zearalenone. Three collaborators reported false positives for both alpha-zearalenol and zearalenone. The within-laboratory CV values based on blind duplicates were 22.6% for alpha zearalenol and 31.4% for zearalenone. The CV values based on laboratory-sample interaction were 25.6 and 33.8% for alpha-zearalenol and zearalenone, respectively. The CV values for naturally contaminated samples (including duplicates) were 47.0% for alpha-zearalenol and 37.7% for zearalenone. The method has been adopted official first action. PMID- 2932427 TI - Ocimum basilicum in acne vulgaris--a controlled comparison with a standard regime. PMID- 2932428 TI - Peritoneoscopy in undiagnosed ascites. PMID- 2932429 TI - Identification of a temperature-sensitive mutation in the htpR (rpoH) gene of Escherichia coli K-12. AB - A new mutation in the htpR (rpoH) gene of Escherichia coli K-12 was identified. The mutation resulted in a temperature-sensitive phenotype in terms of cell growth and bacteriophage lambda development. As in the case of the classical htpR tsn-165 mutation, synthesis of heat shock polypeptides was not induced in strains carrying the mutation described here. PMID- 2932430 TI - phs Locus of Escherichia coli, a mutation causing pleiotropic lesions in metabolism, is an rpoA allele. AB - The phs mutation, which causes a pleiotropic growth defect, has been mapped and shown to be an allele of rpoA, the gene for the alpha subunit of RNA polymerase. The mutation is shown to cause a transcription defect in the arabinose operon, araBAD. PMID- 2932431 TI - Structural and related functional changes in sarcoplasmic reticulum induced by long-chain fatty acids. AB - The effect of palmitic and oleic acids on Ca2+-ATPase activity in coupled preparations of sarcoplasmic reticulum isolated from rabbit hind leg muscle have been compared with their effects on vesicles uncoupled with Ca2+ ionophore, A23187. Palmitate at 2 microM X mg protein-1 has no significant effect on enzyme activity and does not uncouple catalytic activity from calcium accumulation within the vesicles. Oleic acid at 1 microM X mg protein-1 uncouples the vesicles, whereas 2 microM X mg protein-1 completely inhibits Ca2+-ATPase activity. Fluorescence anisotropy of diphenylhexatriene is not significantly altered by palmitate, but a large transient increase in motion of the probe is observed with addition of oleic acid. The effects of oleic acid on enzyme activity are not mediated via an effect on the bulk properties of the hydrophobic domain of the membrane lipids. PMID- 2932432 TI - The polymerase subunit of DNA polymerase III of Escherichia coli. I. Amplification of the dnaE gene product and polymerase activity of the alpha subunit. AB - The Escherichia coli dnaE gene, which encodes the alpha subunit of DNA polymerase III (pol III) holoenzyme, has been cloned in a plasmid containing the PL promoter of phage lambda and thermally induced to overproduce the alpha subunit. In cells carrying this plasmid (pKH167), the alpha subunit was amplified, after heat induction, to a level of about 0.2% of the total cellular protein. Polymerase activity was assayed in three ways: (i) gap-filling by pol III holoenzyme and subassemblies of it, (ii) the extensive replication of a primed, single-stranded DNA circle only by pol III holoenzyme, and (iii) complementation of a crude, inactive pol III holoenzyme (temperature-sensitive dnaE mutant fraction) in replication of a primed, single-stranded DNA circle. Amplification of the alpha subunit raised the polymerase level 10-fold in assay (i), indicative of the dependence of pol III gap-filling activity on this polypeptide; pol III holoenzyme activity remained unaffected (assay (ii)), but the complementation activity was raised 5-fold (assay (iii)). Thus, the elevated alpha subunit (free or in a subassembly form) can substitute in vitro for a defective alpha subunit in pol III holoenzyme, but cannot increase the in vivo level of about eight pol III holoenzyme molecules per cell. This low level of pol III holoenzyme is fixed in wild type cells (bearing no plasmid) despite the presence of a 5-fold excess of the alpha subunit, as inferred from the various assays. These results suggest that the low level of pol III holoenzyme is determined by a factor or factors other than the level of the alpha subunit. PMID- 2932433 TI - The toxicity of acetaminophen and N-acetyl-p-benzoquinone imine in isolated hepatocytes is associated with thiol depletion and increased cytosolic Ca2+. AB - The effects of acetaminophen and its major toxic metabolite, N-acetyl-p benzoquinone imine (NAPQI), have been investigated in hepatocytes isolated from 3 methylcholanthrene-pretreated and -untreated rats, respectively. The two compounds produced qualitatively similar changes although the quinone imine was toxic with shorter incubations periods and at lower doses. Both agents caused an elevation of cytosolic Ca2+, assessed by phosphorylase a activity, which was accompanied by the concomitant appearance of plasma membrane blebs. A loss of mitochondrial Ca2+ was also observed. This disruption of Ca2+ homeostasis always preceded cell death. Studies with NAPQI showed that low doses were able to cause complete Ca2+ release from isolated liver mitochondria which was accompanied by pyridine nucleotide oxidation and preceded membrane damage. NAPQI also produced a rapid, dose-dependent depletion of both cytosolic and mitochondrial reduced glutathione as well as a loss of protein-bound SH groups. This loss of protein thiols may have been responsible for the observed inhibition of the high-affinity Ca2+-ATPase activity of the plasma membrane fraction isolated from NAPQI-treated cells. In addition, NAPQI inhibited microsomal Ca2+ uptake which would further contribute to the elevation in cytosolic Ca2+. Our results suggest that acetaminophen and N-acetyl-p-benzoquinone imine exert their cytotoxic effects via a disruption of Ca2+ homeostasis secondary to the depletion of soluble and protein-bound thiols. This mechanism may prove to be of general applicability to a variety of hepatotoxins. PMID- 2932434 TI - Characterization of peptides cleaved by plasmin from the C-terminal polymerization domain of human fibrinogen. AB - The C-terminal region of the fibrinogen gamma chain is known to participate in several functional interactions including fibrin polymerization. This part of the molecule is retained on the gamma chain of fragment D (FgD) when fibrinogen is digested by plasmin in the presence of calcium to produce the fragment D-fragment E (FgD X FgE) complex but is lost if FgD is prepared in the absence of calcium. In an attempt to characterize the C-terminal polymerization domain we have used three techniques to examine this further degradation of FgD following the addition of EDTA and plasmin. Analysis of the digestion by sodium dodecyl sulfate polyacrylamide gel electrophoresis showed a progressive cleavage of the gamma chain to two small remnants. The polymerization-inhibitory activity of the whole digest was studied using acid-solubilized fibrin. A progressive loss of inhibitory activity was associated with gamma chain shortening, reaching greater than a 120-fold reduction at the end of digestion. The cleavage of peptides was followed by reverse-phase high performance liquid chromatography and the release of a characteristic peptide triplet was associated with gamma chain cleavage. Manual sequencing, amino acid analysis, and fast atom bombardment mass spectrometry established the three peptides as gamma 303-356, 357-373, and 374 405. These peptides have sequences in common with those peptides recently reported by other investigators to be potent polymerization inhibitors. However, when a mixture of the three peptides was added in a 200-fold molar excess to polymerizing fibrin, no inhibitory activity could be demonstrated. It is concluded that the C-terminal polymerization domain of fibrinogen may be an extended region which includes the sequence gamma 303-405, when this is contiguous with the remainder of the gamma chain. PMID- 2932435 TI - Effects of Ca2+ on the conformation and enzymatic activity of smooth muscle myosin. AB - The influence of Ca2+ on the enzymatic and physical properties of smooth muscle myosin was studied. The actin-activated ATPase activity of phosphorylated gizzard myosin and heavy meromyosin is higher in the presence of Ca2+ than in its absence, but this effect is found only at lower MgCl2 concentrations. As the MgCl2 concentration is increased, Ca2+ sensitivity is decreased. The concentration of Ca2+ necessary to activate ATPase activity is higher than that required to saturate calmodulin. The similarity of the pCa dependence of ATPase activity and of Ca2+ binding to myosin and the competition by Mg2+ indicate that these effects involved the Ca2+-Mg2+ binding sites of gizzard myosin. For the actin dependence of ATPase activity of phosphorylated myosin at low concentrations of MgCl2, both Vmax and Ka are influenced by Ca2+. The formation of small polymers by phosphorylated myosin in the presence of Ca2+ could account for the alteration in the affinity for actin. For the actin dependence of phosphorylated heavy meromyosin at low MgCl2 concentrations, Ca2+ induces only an increase in Vmax. To detect alterations in physical properties, two techniques were used: viscosity and limited papain hydrolysis. For dephosphorylated myosin, 6 S or 10 S, Ca2+-dependent effects are not detected using either technique. However, for phosphorylated myosin the decrease in viscosity corresponding to the 6 S to 10 S transition is shifted to lower KCl concentrations by the presence of Ca2+. In addition, a Ca2+ dependence of proteolysis rates is observed with phosphorylated myosin but only at low ionic strength, i.e. under conditions where myosin assumes the folded conformation. PMID- 2932436 TI - The interaction of fibronectin fragments with fibroblastic cells. AB - We have examined the interaction of the purified cell-binding domain of fibronectin with fibroblastic baby hamster kidney cells. When the cell-binding region of fibronectin is part of a large 75,000-dalton fragment, the direct binding of the tritium-labeled fragment to cells in suspension can be observed. There is a single class of 10(5) sites/cell with an apparent dissociation constant of 4 X 10(-7) M. When the cell-binding region is part of a smaller 11,500-dalton fragment, an interaction with cells can only be observed indirectly via inhibition assays. The apparent affinity of this fragment for the cell surface fibronectin receptor is low. This 11,500-dalton fragment competitively inhibits both the direct binding of soluble [3H]fibronectin to cells in suspension and the spreading of cells on fibronectin-coated substrates, suggesting that the fragment binds to the same receptor site as intact fibronectin. Possible models describing the mechanism of the interaction of fibronectin with its receptor are proposed. PMID- 2932437 TI - Differential trace labeling of calmodulin: investigation of binding sites and conformational states by individual lysine reactivities. Effects of beta endorphin, trifluoperazine, and ethylene glycol bis(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid. AB - The Ca2+-dependent association of beta-endorphin and trifluoperazine with porcine testis calmodulin, as well as the effects of removing Ca2+ by ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) treatment, were investigated by the procedure of differential kinetic labeling. This technique permitted determination of the relative rates of acylation of each of the epsilon amino groups of the seven lysyl residues on calmodulin by [3H]acetic anhydride under the different conditions. In all cases, less than 0.52 mol of lysyl residue/mol of calmodulin was modified, thus ensuring that the labeling pattern reflects the microenvironments of these groups in the native protein. Lysines 75 and 94 were found to be the most reactive amino groups in Ca2+-saturated calmodulin. In the presence of Ca2+ and under conditions where beta-endorphin and calmodulin were present at a molar ratio of 2.5:1, the amino groups of lysines 75 and 148 were significantly reduced in reactivity compared to calmodulin alone. At equimolar concentrations of peptide and protein, essentially the same result was obtained except that the magnitudes of the perturbation of these two lysines were less pronounced. With trifluoperazine, at a molar ratio to calmodulin of 2.5:1, significant perturbations of lysines 75 and 148, as well as Lys 77, were also found. These results further substantiate previous observations of a commonality between phenothiazine and peptide binding sites on calmodulin. Lastly, an intriguing difference in Ca2+-mediated reactivities between lysines 75 and 77 of calmodulin is demonstrated. In the Ca2+-saturated form of the protein, both lysines are part of the long connecting helix between the two homologous halves of the protein (Babu, Y. S., Sack, J. S., Greenhough, T. G., Bugg, C. E., Means, A. R., and Cook, W. J. (1985) Nature 315, 37-40). Yet, Lys 75 increases in reactivity some 25-fold, compared to only a 2-fold change for Lys 77, in going from EGTA-treated to Ca2+-saturated calmodulin. Thus, the microenvironment of Lys 75 is markedly altered upon Ca2+ binding, and this linker region between the two globular lobes of the protein appears to be quite important in the interaction of calmodulin with inhibitory molecules and perhaps activatable enzymes. PMID- 2932438 TI - Extracellular ATP perturbs transmembrane ion fluxes, elevates cytosolic [Ca2+], and inhibits phagocytosis in mouse macrophages. AB - In addition to its important role in intracellular metabolic pathways, ATP appears to function as a neurotransmitter in mammalian neurones. The extracellular effects of ATP are not restricted to neurones. We describe the effects of ATP on transmembrane fluxes of monovalent and divalent cations and on phagocytosis in the J774 mouse macrophage cell line and in mouse macrophages elicited by intraperitoneal injection of thioglycollate broth. Of all nucleotides tested, only ATP is capable of depolarizing the macrophage plasma membrane potential, promoting Na+ influx and K+ efflux, effecting an increase in intracellular free Ca2+, and inhibiting phagocytosis. Nonhydrolyzable ATP analogs had no effect on membrane permeability or phagocytosis. The effect mediated by ATP is not accompanied by an increase in membrane permeability to nucleotides, indicating that the action of ATP is restricted to the external surface of macrophages. PMID- 2932439 TI - Fructose 6-phosphate prevents the proteolyzed derivative of Escherichia coli phosphofructokinase from dissociation and inactivation. AB - N-terminal sequence analysis shows that the limited proteolysis of Escherichia coli phosphofructokinase results in the removal of the 40-50 C-terminal residues of each chain. When tetrameric, this proteolyzed derivative is still active albeit insensitive to allosteric effectors (Le Bras, G., and Garel, J.-R. (1982) Biochemistry 21, 6656-6660). In the absence of fructose 6-phosphate, the proteolyzed phosphofructokinase spontaneously loses its activity and dissociates into dimeric species. This inactivation/dissociation is slowed down by the binding of fructose 6-phosphate to only part of the sites; it is completely prevented by the saturation of all four fructose 6-phosphate sites. The other substrate ATP does not protect the proteolyzed phosphofructokinase against this inactivation/dissociation. This inactivation/dissociation is not due to denaturation and can be reversed in some conditions by the addition of fructose 6 phosphate. The active tetrameric structure of phosphofructokinase is stable when either the C-terminal segment is not removed or the fructose 6-phosphate sites are occupied. PMID- 2932440 TI - Conformational responses of the tryptic cleavage products of the Ca2+-ATPase of sarcoplasmic reticulum. AB - Trypsin cleaves the Ca2+-ATPase of sarcoplasmic reticulum into two major fragments (A and B), followed by subsequent cleavage into smaller peptides. Although the ATP-dependent Ca2+ transport is still observed after cleavage of the ATPase into the A and B fragments, the Ca2+ transport energized by acetyl phosphate is strongly inhibited. Covalent labeling of the Ca2+-ATPase by fluorescein 5'-isothiocyanate inhibited both the ATP and acetyl phosphate dependent Ca2+ transport. Vanadate protected the A and B fragments from further hydrolysis and preserved the ability of the cleaved Ca2+-ATPase to form crystals and to show the characteristic conformational changes in response to Ca2+ and EGTA that are observed with the intact enzyme. The protective effect of vanadate may be useful for the isolation of the A and B fragments in functional form. PMID- 2932441 TI - Reaction mechanism of the membrane-bound ATPase of submitochondrial particles from beef heart. AB - Submitochondrial particles from beef heart, washed with dilute solutions of KCl so as to activate the latent, membrane-bound ATPase, F1, may be used to study single site catalysis by the enzyme. [gamma-32P]ATP, incubated with a molar excess of catalytic sites, a condition which favors binding of substrate in only a single catalytic site on the enzyme, is hydrolyzed via a four-step reaction mechanism. The mechanism includes binding in a high affinity catalytic site, Ka = 10(12)M-1, a hydrolytic step for which the equilibrium constant is near unity, and two product release steps in which Pi dissociates from catalytic sites about 10 times more rapidly than ADP. Catalysis by the membrane-bound ATPase also is characterized by a 10(6)-fold acceleration in the rate of net hydrolysis of [gamma-32P]ATP, bound in the high affinity catalytic site, that occurs when substrate is made available to additional catalytic sites on the enzyme. These aspects of the reaction mechanism of the ATPase of submitochondrial particles closely parallel the reaction mechanism determined for solubilized, homogeneous F1 (Grubmeyer, C., Cross, R. L., and Penefsky, H. S. (1982) J. Biol. Chem. 257, 12092-12100). The finding that removal of the enzyme from the membrane does not significantly alter the properties of single site catalysis lends support to models of ATP synthesis in oxidative phosphorylation, catalyzed by membrane-bound F1, that have been based on the study of the soluble enzyme. PMID- 2932442 TI - Energy-dependent dissociation of ATP from high affinity catalytic sites of beef heart mitochondrial adenosine triphosphatase. AB - Incubation of [gamma-32P]ATP with a molar excess of the membrane-bound form of mitochondrial ATPase (F1) results in binding of the bulk of the radioactive nucleotide in high affinity catalytic sites (Ka = 10(12) M-1). Subsequent initiation of respiration by addition of succinate or NADH is accompanied by a profound decrease in the affinity for ATP. About one-third of the bound radioactive ATP appears to dissociate, that is, the [gamma-32P]ATP becomes accessible to hexokinase. The NADH-stimulated dissociation of [gamma-32P]ATP is energy-dependent since the stimulation is inhibited by uncouplers of oxidative phosphorylation and is prevented by respiratory chain inhibitors. The rate of the energy-dependent dissociation of ATP that occurs in the presence of NADH, ADP, and Pi is commensurate with the measured initial rate of ATP synthesis in NADH supported oxidative phosphorylation catalyzed by the same submitochondrial particles. Thus, the rate of dissociation of ATP from the high affinity catalytic site of submitochondrial particles meets the criterion of kinetic competency under the conditions of oxidative phosphorylation. These experiments provide evidence in support of the argument that energy conserved during the oxidation of substrates by the respiratory chain can be utilized to reduce the very tight binding of product ATP in high affinity catalytic sites and to promote dissociation of the nucleotide. PMID- 2932443 TI - Reversible dissociation of dog cardiac myosin regulatory light chain 2 and its influence on ATP hydrolysis. AB - The regulatory light chains of dog heart myosin were removed by digestion with myopathic hamster neutral protease. The heavy chains were also cleaved to an extent of 15%, but a homogeneous, rod-free LC2-deficient myosin was obtained by ion-exchange chromatography. A similar approach was used to prepare LC2-deficient heavy meromyosin. Neither Ca2+- nor K+-EDTA-activated ATPases were affected by LC2 removal. The Lineweaver-Burk plots for actin-activated ATPase in 25 mM KCl were biphasic giving a Vmax of 1.54 s-1 for control and LC2-recombined myosins and 1.08 s-1 for LC2-deficient myosin at low actin concentrations. At high actin concentrations, the Vmax for control and recombined myosins was 2.33 s-1 and 1.39 s-1 for LC2-deficient myosin. Increasing the KCl concentration in the reaction mixtures resulted in more linear plots without suppressing the 35-45% decrease in Vmax that accompanied LC2 removal. The results from assays with control and LC2 deficient heavy meromyosin performed in the absence of KCl, paralleled those obtained with myosin. The latter was also assayed in the presence of equimolar concentrations of C-protein in 50 mM KCl: C-protein induced a significant increase in the actin-activated ATPase of both control and LC2-recombined myosins, with no effect on LC2-deficient myosin. The Vmax for actin-activation in the presence of C-protein was 2.38 s-1, 0.83 s-1, and 1.71 s-1 for control, LC2 deficient, and recombined myosins, respectively. The enhancement of actin activation in both the control and LC2-recombined myosins represents a possible role for C-protein in a LC2-mediated potentiation of actomyosin ATPase. PMID- 2932444 TI - Carbohydrates of lysosomal enzymes secreted by Tetrahymena pyriformis. AB - The carbohydrate structures of acid phosphatase and alpha-glucosidase secreted into culture medium by Tetrahymena pyriformis strain W were studied. Their asparagine-linked sugar chains were quantitatively liberated as radioactive oligosaccharides from their polypeptide moieties by controlled hydrazinolysis followed by N-acetylation and NaB3H4 reduction. The approximate amounts of total sugar chains liberated from 1 mol each of acid phosphatase and alpha-glucosidase were 6 and 4 mol, respectively. Paper electrophoresis revealed that only neutral oligosaccharides were obtained from both enzymes. The oligosaccharide fraction from acid phosphatase was separated into seven components by Bio-Gel P-4 column chromatography while that from alpha-glucosidase was resolved into three components. The structures of these oligosaccharides were determined by sequential glycosidase digestion in combination with methylation analysis. The sugar chains of the two enzymes can be primarily classified as high mannose-type oligosaccharides. However, they have the following characteristic features: 1) their common core is not the usual Man5 . GlcNAc2 structure, it is Man3 . GlcNAc2; 2) some of the sugar chains of acid phosphatase have 1 approximately 3 glucose residues linked to the nonreducing terminal Man alpha 1----2 residue. The structural characteristics of the sugar moieties of the two enzymes indicate that they might be produced by the so-called "alternate pathway," in which lipid linked Glc3 . Man5 . GlcNAc2 functions as an oligosaccharide donor. PMID- 2932445 TI - Carbamoyl-phosphate synthetases from Neurospora crassa. Immunological relatedness of the enzymes from Neurospora, bacteria, yeast, and mammals. AB - Neurospora crassa contains two carbamoyl-phosphate synthetases: a mitochondrial enzyme (CPS-A) which supplies carbamoyl phosphate for arginine biosynthesis, and a nuclear enzyme whose product is used for the synthesis of pyrimidines. We have prepared antiserum against a highly purified preparation of the large subunit of CPS-A and have used the antiserum to demonstrate that the large subunit is, like most mitochondrially localized proteins, initially synthesized as a higher molecular weight precursor. The CPS-A antiserum cross-reacts with the nuclear enzyme, allowing us to identify the product of the complex N. crassa pyr-3 genetic locus as a protein with a subunit molecular weight of 180,000. Finally, we have found that the CPS-A antiserum also cross-reacts with carbamoyl-phosphate synthetases from bacteria, yeast, and mammals. The immunological relatedness of carbamoyl-phosphate synthetases from such diverse species suggests that the protein sequences required for carbamoyl phosphate production have been highly conserved during the course of evolution. PMID- 2932447 TI - Distances between the functional sites of the (Ca2+ + Mg2+)-ATPase of sarcoplasmic reticulum. AB - Luminescence energy transfer measurements have been used to determine the distances between the two high affinity Ca2+ binding-transport sites of the (Ca2+ + Mg2+)-ATPase of skeletal muscle sarcoplasmic reticulum. The lanthanide Tb3+ situated at one high affinity Ca2+ site was used as the transfer donor, and acceptors at the other Ca2+ site were the lanthanides Nd3+, Pr3+, Ho3+, or Er3+. Terbium bound to the enzyme was excited directly with a pulsed dye laser. Analysis of the changes in the terbium luminescence lifetime due to the presence of the acceptor indicates that the distance between the Ca2+ sites is 10.7 A. The distance between the Ca2+ sites and the nucleotide-binding catalytic site was determined using Tb3+ at the Ca2+ sites and either trinitrophenyl nucleotides (TNP-N) or fluorescein 5-isothiocyanate (FITC) in the catalytic site as energy acceptors. The R0 values for the Tb-acceptor pairs are approximately 30 and approximately 40 A for TNP-N and FITC, respectively. The distance between Tb3+ at the Ca2+ sites and TNP-ATP at the nucleotide site is approximately 35 A and that between the Ca2+ sites and the FITC labeling site is approximately 47 A. Considerations of the molecular dimensions of the ATPase polypeptide indicate that while the two Ca2+ sites are close to each other, the Ca2+ sites and the nucleotide site are quite remote in the three-dimensional structure of the enzyme. PMID- 2932446 TI - The heavy chain of macrophage myosin is phosphorylated at the tip of the tail. AB - Myosin purified from rabbit alveolar macrophages has been shown previously to be phosphorylated on the rod portion of the heavy chain and on the 20-kDa light chains (Trotter, J.A. (1982) Biochem Biophys. Res. Commun. 106, 1071-1077). Phosphorylation of the 20-kDa light chains by endogenous kinase activity is associated with a significant enhancement of the actin-activated MgATPase activity (Trotter, J.A., and Adelstein, R.S. (1979) J. Biol. Chem. 254, 8781 8785), whereas the function of heavy-chain phosphorylation is unknown. The isolated heavy chains of myosin purified from freshly harvested cells contain between 0.4 and 1.5 mol of PO4/mol of heavy chain, all esterified to serine residues. Using myosin phosphorylated by incubating living unstimulated macrophages in the presence of 32Pi, two-dimensional thin-layer mapping of tryptic peptides derived from heavy chains yields four phosphopeptides, which are phosphorylated to different extents. Limited trypsin digestion of similar radioactive myosin removes all radioactivity from the heavy chain while reducing its apparent molecular mass by less than 10 kDa. It is concluded that the heavy chain of macrophage myosin is phosphorylated on as many as four serines within 10 kDa of the tip of the tail. PMID- 2932448 TI - Structure of the heparan sulfate-protein linkage region. Demonstration of the sequence galactosyl-galactosyl-xylose-2-phosphate. AB - We have treated bovine lung heparan sulfate with alkaline [3H]borohydride to end label the chains with [3H]xylitol. After subsequent periodate oxidation-alkaline elimination products were separated by gel permeation and ion exchange chromatography. The linkage region fragment expected to have 2 galactoses and 1 [3H]xylitol residue appeared in the tetra-/trisaccharide region after gel filtration and was bound to the anion exchange resin. A similar negatively charged fragment, expected to have 2 galactoses, 1 xylose and 1 serine, was isolated after periodate oxidation-alkaline elimination of unlabeled heparan sulfate. The negative charge was due to the presence of alkaline phosphatase labile phosphate ester. The molar ratio of galactose:phosphate:xylose was 2.17:1.19:1.00. The phosphate ester was associated with the xylose/[3H] xylitol moiety as indicated by the formation of phosphoxylose/-xylitol by beta galactosidase digestion of the phosphorylated trisaccharide. Furthermore, orcinol reactivity disappeared after periodate oxidation of the dephosphorylated trisaccharide. The phosphate ester must be located to C-2 of xylose/xylitol as the 1-3H radioactivity could be released by periodate oxidation when it was preceded by alkaline phosphatase treatment. It is estimated that almost every chain of heparan sulfate carries 2-phosphoxylose. It would be of interest to know if glycosaminoglycan chains that are artificially initiated onto exogeneous beta D-xylosides also acquire the 2-phosphoxylose moiety. PMID- 2932449 TI - Calcium-insensitive binding of heavy meromyosin to regulated actin at physiological ionic strength. AB - Several conflicting reports have been made regarding the affinity of myosin heads (subfragment 1 and heavy meromyosin (HMM) for regulated actin (actin complexed with tropomyosin and troponin) at low ionic strength (mu = 18-50 mM) and whether or not this interaction is Ca2+ sensitive (Chalovich, J. M., and Eisenberg, E. (1982) J. Biol. Chem. 257, 2432-2437; Chalovich, J. M., and Eisenberg, E. (1984) Biophys. J. 45, 221a; Wagner, P. D., and Stone, D. B. (1983) Biochemistry 22, 1334-1342; and Wagner, P. D. (1984) Biochemistry 23, 5950-5956). Since the low ionic strengths used in the above studies do not represent the physiological ionic strength under which intact muscle exhibits Ca2+-dependent tension development, we investigated the possibility of whether a Ca2+-dependent regulated actin-HMM interaction could be observed at physiological ionic strength (mu = 134 mM, pH 7.4) and in the presence of ATP (at 23-24 degrees C). Direct binding of HMM to varied concentrations of regulated actin (87.7-221 microM free actin) was measured by sedimentation in an air-driven ultracentrifuge. Under the above conditions, we found that the regulated actin activation of HMM-Mg2+-ATPase was about 94% inhibited in the absence of Ca2+ although the association constant (Ka) is only moderately affected in the presence of Ca2+. These results are similar to those obtained by Chalovich and Eisenberg (1982 and 1984) with subfragment 1 and HMM, respectively, at low ionic strength and support their suggestion that in solution tropomyosin-troponin may not act totally by physically blocking the formation of cross-bridges with actin, but instead may act to inhibit a kinetic step in the overall ATPase rate. Whether this holds true in more intact systems (e.g. myosin, thick filaments) remains to be determined. Our results also show a good correlation between levels of ATPase activation and HMM binding by unregulated actin and in regulated actin in the presence of Ca2+. PMID- 2932450 TI - A conformational transition in gizzard heavy meromyosin involving the head-tail junction, resulting in changes in sedimentation coefficient, ATPase activity, and orientation of heads. AB - Gizzard heavy meromyosin (HMM) sediments in the ultracentrifuge as a single peak, whose sedimentation coefficient (S20,w) decreases from 9 to 7.5 S upon increasing the NaCl concentration from 0.02 to 0.3 M. This decrease is accompanied by a parallel increase in Mg2+-ATPase activity, suggesting that both changes have a common molecular basis. Phosphorylation decreases S20,w and increases ATPase activity, while ATP increases S20,w. Sedimentation equilibrium studies indicate that HMM undergoes no detectable aggregation at 0.02 or 0.4 M NaCl, remaining monomeric with a molecular weight of 3.4 X 10(5). In contrast, S20,w of subfragment 1 does not change with changes in ionic strength, and its ATPase activity does not decrease at low ionic strengths. Electron micrographs of samples of HMM prepared at low ionic strength show that up to half of the molecules are flexed, i.e. the heads are bent at the neck and project back toward the tail, while the remaining molecules have either one or both of the heads pointing away from the tail. In samples prepared at high ionic strength only about 10% of the molecules are flexed. There is a linear relationship between the fraction of flexed molecules and S20,w, with no significant bending or folding of the tail and no detectable change in the shape of the heads. This correlation suggests that the changes in ATPase activity and S20,w may be a result of the reorientation of the heads. PMID- 2932452 TI - Cytoskeletal architecture of isolated mitotic spindle with special reference to microtubule-associated proteins and cytoplasmic dynein. AB - We have studied cytoskeletal architectures of isolated mitotic apparatus from sea urchin eggs using quick-freeze, deep-etch electron microscopy. This method revealed the existence of an extensive three-dimensional network of straight and branching crossbridges between spindle microtubules. The surface of the spindle microtubules was almost entirely covered with hexagonally packed, small, round button-like structures which were very uniform in shape and size (approximately 8 nm in diameter), and these microtubule buttons frequently provided bases for crossbridges between adjacent microtubules. These structures were removed from the surface of microtubules by high salt (0.6 M NaCl) extraction. Microtubule associated proteins (MAPs) and microtubules isolated from mitotic spindles which were mainly composed of a large amount of 75-kD protein and some high molecular mass (250 kD, 245 kD) proteins were polymerized in vitro and examined by quick freeze, deep-etch electron microscopy. The surfaces of microtubules were entirely covered with the same hexagonally packed round buttons, the arrangement of which is intimately related to that of tubulin dimers. Short crossbridges and some longer crossbridges were also observed. High salt treatment (0.6 M NaCl) extracted both 75-kD protein and high molecular weight proteins and removed microtubule buttons and most of crossbridges from the surface of microtubules. Considering the relatively high amount of 75-kD protein among MAPs isolated from mitotic spindles, it is concluded that these microtubule buttons probably consist of 75-kD MAP and that some of the crossbridges in vivo could belong to MAPs. Another kind of granule, larger in size (11-26 nm in diameter), was also on occasion associated with the surface of microtubules of mitotic spindles. A fine sidearm sometimes connected the larger granule to adjacent microtubules. Localization of cytoplasmic dynein ATPase in the mitotic spindle was investigated by electron microscopic immunocytochemistry with a monoclonal antibody (D57) against sea urchin sperm flagellar 21S dynein and colloidal gold-labeled second antibody. Immunogold particles were closely associated with spindle microtubules. 76% of these were within 50 nm and 55% were within 20 nm from the surface of the microtubules. These gold particles were sporadically found on both polar and kinetochore microtubules of half-spindles at both metaphase and anaphase. They localized also on the microtubules between sister chromatids in late anaphase. These data indicate that cytoplasmic dynein is attached to the microtubules in sea urchin mitotic spindles.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2932451 TI - Effects of actin filament cross-linking and filament length on actin-myosin interaction. AB - We have used two actin-binding proteins of the intestinal brush border, TW 260/240 and villin, to examine the effects of filament cross-linking and filament length on myosin-actin interactions. TW 260/240 is a nonerythroid spectrin that is a potent cross-linker of actin filaments. In the presence of this cross-linker we observed a concentration-dependent enhancement of skeletal muscle actomyosin ATPase activity (150-560% of control; maximum enhancement at a 1:70-80 TW 260/240:actin molar ratio). TW 260/240 did not cause a similar enhancement of either acto-heavy meromyosin (HMM) ATPase or acto-myosin subfragment-one (S1) ATPase. Villin, a Ca2+-dependent filament capping and severing protein of the intestinal microvillus, was used to generate populations of actin filaments of various lengths from less than 20 nm to 2.0 microns; (villin:actin ratios of 1:2 to 1:4,000). The effect of filament length on actomyosin ATPase was biphasic. At villin:actin molar ratios of 1:2-25 actin-activated myosin ATPase activity was inhibited to 20-80% of control values, with maximum inhibition observed at the highest villin:actin ratio. The ATPase activities of acto-HMM and acto-S1 were also inhibited at these short filament lengths. At intermediate filament lengths generated at villin:actin ratios of 1:40-400 (average lengths 0.26-1.1 micron) an enhancement of actomyosin ATPase was observed (130-260% of controls), with a maximum enhancement at average filament lengths of 0.5 micron. The levels of actomyosin ATPase fell off to control values at low concentrations of villin where filament length distributions were almost those of controls. Unlike intact myosin, the actin-activated ATPase of neither HMM nor S1 showed an enhancement at these intermediate actin filament lengths. PMID- 2932453 TI - Effect of serotonin and its antagonist ketanserin on pial vessels. AB - The effect of serotonin (5-HT) and its antagonist ketanserin on the cerebral circulation was investigated in two series totaling 24 cats using the cranial window technique. 5-HT elicited a marked dilatation of small pial arteries, whereas large arteries tended to constrict. Intravenous administration of ketanserin reversed the constriction of large arteries, causing dilatation, and reduced the extent of small arteries' dilatation. In a randomized study, i.v. administration of ketanserin in its solvent versus the solvent alone revealed a strong dilatatory effect of the solvent on pial arteries (17 +/- 1.8%), which partly jeopardized a possible constrictory effect of ketanserin, as ketanserin plus solvent induced less dilatation of small pial arteries than the solvent alone. The present data support the view that serotonin exerts a dual effect on cerebral arteries, namely, dilatation of small and constriction of large vessels. The antagonist ketanserin reverses this effect, but the strong dilatatory effect of the solvent alone masks the antiserotoninergic effect. PMID- 2932454 TI - Early postnatal development of transport functions in the rabbit choroid plexus. AB - The development of transport functions in the rabbit choroid plexus was followed postnatally up to 2 months after birth. The activity of ouabain-sensitive Na+, K+ ATPase in newborn rabbit choroid plexus composes about one-fourth (lateral and third ventricle) to one-half (fourth ventricle) of the activity in the adult animal, and it increases markedly within the first 3 weeks of early life. A similar profile of postnatal changes is observed for the capacity to take up and accumulate the organic base choline, which is about three to five times higher for the adult rabbit than for the newborn animal. This coincides with the maturation of the epithelial cells as well as with the development of the sympathetic nerve supply in the choroid plexus. The results suggest that energy dependent translocation systems influenced by local sympathetic nerves in the choroid plexus, at the interface between blood and CSF, have a functional role shortly after birth. PMID- 2932455 TI - Management of refractory acne. PMID- 2932456 TI - The cytoskeletal system of red blood cells. PMID- 2932457 TI - Derivatization of secondary amines with 2-naphthalene-sulfonyl chloride for high performance liquid chromatographic analysis of spectinomycin. AB - A normal-phase high-performance liquid chromatographic (HPLC) method has been developed for the assay of spectinomycin hydrochloride and spectinomycin sulfate for detection at 254 nm. The method involves pre-column derivatization of secondary amines of spectinomycin with 2-naphthalenesulfonyl chloride (NSCl) using a catalyst. Lincomycin, 1-methylpyrrole, 2-acetyl-1-methylpyrrole, and 2 acetyl-pyrrole act as catalysts for sulfonylation of spectinomycin. Without a catalyst, the derivatization reaction forms a considerable amount of actinospectinoic acid, a degradation compound of spectinomycin, and peak area:weight ratio of the derivative is approximately 15% lower than those with the catalyst. Following derivatization the sample is extracted and chromatographed on a normal-phase silica column with detection at 254 nm. The method is applicable for the analysis of both the hydrochloride and sulfate salt forms of spectinomycin. All the known degradation compounds of spectinomycin such as actinamine, actinospectinoic acid and the biosynthesis intermediates, dihydrospectinomycin diastereoisomers, are completely separated with this method. Mass spectrometric data confirms that spectinomycin is derivatized with NSCl at the secondary amines located at positions 6 and 8 of the ring structure. The standard curves for the HPLC assay of spectinomycin hydrochloride and sulfate are linear with correlation coefficients of 0.9997 and 0.9999, respectively over the range of 0.05 mg/ml to 0.3 mg/ml. The relative standard deviations (R.S.D.) of the HPLC assay methods for spectinomycin hydrochloride and sulfate are 0.67% and 0.86%, respectively. Spectinomycin hydrochloride and sulfate bulk drugs were assayed by the HPLC method and compared to gas-liquid chromatography and microbiological assay results. The HPLC method was used to assay spectinomycin in a veterinary formulation, Linco-Spectin soluble powder. The sensitivity of the HPLC assay was determined to be approximately 4 ng sample load on the column, which suggests applicability in serum and residue level studies. PMID- 2932458 TI - Analysis of 5'-deoxy-5-fluorouridine and 5-fluorouracil in human plasma and urine by high-performance liquid chromatography. AB - A relatively simple and sensitive high-performance liquid chromatographic (HPLC) method is described for measuring the two anticancer drugs 5'-deoxy-5 fluorouridine (5'dFUR) and 5-fluorouracil (5-FU) in human plasma and urine. The procedure for plasma includes solvent extraction using ethyl acetate-isopropyl alcohol (85:15) followed by silica gel column chromatography to separate these compounds from constituents normally occurring in plasma. The analysis by reversed-phase HPLC is performed on a phenyl column using an aqueous mobile phase with ultraviolet detection (280 nm). The overall recovery from plasma was 61% and 65% for 5'dFUR and 5-FU, respectively. The sensitivity limit of the assay for both compounds was 50 ng/ml of plasma. Analysis of these compounds in urine did not require the silica column chromatography isolation step. PMID- 2932459 TI - Relationship of uteroplacental blood flow to the placental clearance of maternal dehydroepiandrosterone through estradiol formation in the pregnant baboon. AB - The theory that maternal intervillous blood flow is a major determinant of the rate at which the placenta clears androgenic steroid precursors through estrogen formation has never been tested by direct experimentation. We studied the effects of graded reductions in maternal distal aortic blood flow (Qda) on the placental clearance (PC) of dehydroepiandrosterone (D) through estradiol (E2) formation in pregnant baboons near term. A continuous iv infusion of [7-3H]D and [4-14C]E2 was administered to four pregnant baboons (Papio anubis) at 155-165 days gestation (term, 184 days) for 270 min (t0-t270). Maternal Qda was continuously recorded by electromagnetic flow transducer at the aortic bifurcation and altered with an aortic snare device. A 50% reduction in Qda was imposed at t60 and released at t180. Blood samples were collected at 10-min intervals from t30-t60 (control interval), t120-t180 (occlusion interval), and t240-t270 (release interval). All four animals were later studied after pregnancy with an identical infusion for 90 min, with blood samples obtained at 10-min intervals from t30-t90. Equilibrium concentrations of [3H]D, [3H]E2, and [14C]E2 in plasma were determined and the MCR of D (MCR-D), the transfer constant of conversion of D to E2 (rho DE2), and the PC of D through E2 formation (PCDE2) were calculated for each of the three levels of Qda corresponding to the control, occlusion, and release intervals in pregnant animals and under conditions of existing Qda in the nonpregnant state. Control MCR-D during pregnancy (mean +/- SE, 740 +/- 74 liters/day) exceeded MCR D after pregnancy (500 +/- 40 liters/day). MCR-D fell significantly during occlusion (P less than 0.05). Both rho DE2 and PCDE2 decreased uniformly when Qda was reduced by 50% and returned toward the control level with release of the aortic constriction. The mean rho DE2 in pregnant animals was 0.068 +/- 0.0073 (+/- SE), 0.039 +/- 0.0020, and 0.059 +/- 0.0063 during control, occlusion, and release intervals, respectively, all exceeding rho DE2 in the nonpregnant state (0.013 +/- 0.0004). Control mean PCDE2 was 46.3 +/- 8.24 (+/- SE) ml/min; it decreased to 18.9 +/- 2.68 with 50% reduction in Qda and was 35.6 +/- 5.43 when Qda was restored to 75% of the control value. PCDE2 was directly proportional to Qda (r2 = 0.98; P less than 0.01; n = 12) and remained a constant fraction (0.13 +/- 0.002) thereof in all four animals.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2932460 TI - Peripheral serotonin2 receptor blockade does not inhibit 5-hydroxytryptophan induced aldosterone stimulation. AB - To assess the effects of serotonin receptor blockade on 5-hydroxytryptophan (5HTP)-induced aldosterone secretion, we studied six normal men using the serotonin antagonists ketanserin and methysergide. The subjects were studied on three separate occasions, and pretreatment with dexamethasone was given before each study. On two occasions, the pretreatment period also included administration of a serotonin antagonist, either ketanserin (120 mg/day) or methysergide (6 mg/day). On the day of study, the subjects were given a single oral 200-mg dose of 5HTP. Plasma levels of aldosterone increased significantly after 5HTP treatment compared to basal levels during each stage of the study. No significant difference in response in the three studies was found. We conclude that peripheral blockade of serotonin2 receptors does not abolish 5HTP-induced aldosterone stimulation, and that this stimulation is most likely mediated by central pathways. PMID- 2932462 TI - [An occupational health survey on beauticians in Japan. (III). Survey of lumbago]. PMID- 2932461 TI - Quantitative and functional analysis of a human lymphocyte subset with the T helper (Leu 3/T 4+) phenotype and natural killer (NK)-cell characteristics in patients with malignancy. AB - Approximately 20% of normal blood lymphocytes expressing the T-helper (Leu 3/T 4+) surface phenotype display natural killer (NK)-like features such as cytoplasmic granules and the ability to bind NK-cell targets. In this study, we have assessed the frequency, phenotypic features, and functional capabilities of such cells in a variety of lymphoid malignancies or solid tumors. In each patient group, the percentage of granular lymphocytes within the Leu 3/T 4+ T-helper subset was significantly increased. A large percentage of these cells coexpressed the Leu 7 or Leu 15 marker. When Leu 3+ cells from patients with high proportions of such NK-like cells (or Leu 3+-Leu 15+ cells from selected patients) were isolated with a fluorescence-activated cell sorter, these cells did not proliferate in response to allogeneic cells or T-cell mitogens, nor did they provide help for B-cell differentiation. They also did not suppress T-cell proliferative responses or B-cell differentiation. Freshly prepared Leu 3+ granular lymphocytes did not display NK-cell cytotoxic functions. However, after short-term culture in the presence of phytohemagglutinin (PHA), Leu 3+-Leu 15+ cells expressed T-cell growth factor (TCGF) receptors, had a detectable proliferative response to exogenous TCGF, and acquired the ability to lyse NK cell targets. These studies demonstrate that, in a variety of malignancies, the lymphocyte subpopulation expressing the T-helper (Leu 3/T 4+) phenotype may be comprised largely of cells with NK-like features and functional capabilities distinct from those of classical helper T cells. PMID- 2932463 TI - [An occupational health survey on beauticians in Japan. (IV). Relationship of lumbago to body weight]. PMID- 2932464 TI - Encapsulation and capsular types in isolates of Staphylococcus aureus from different sources and relationship to phage types. AB - The relationship of capsular types of Staphylococcus aureus to type of infection, carrier state, and phage type was studied in a collection of 477 isolates from 380 infection sites. Capsular polysaccharides were demonstrated by precipitation and agglutination with 11 monospecific antisera. When only one isolate from each infection was considered, 63% were of type 8 and 16% were of type 5. Of all the isolates tested, over 90% were encapsulated. We did not demonstrate any marked difference in the distribution of capsular types between isolates from the blood stream or purulent processes and isolates from healthy carriers or food. Most isolates from bovine mastitis milk had nontypeable capsules. The capsular type seemed stable in culture, and encapsulation had no apparent influence on susceptibility to phages. Of 27 phage-propagating strains maintained via culture transfer on artificial media over many years, 16 (59%) produced capsules. A striking association between certain phage patterns and capsular types was demonstrated. PMID- 2932465 TI - The mythology of occupational disease consumption. PMID- 2932466 TI - Monoclonal antibodies against complement 3 neoantigens for detection of immune complexes and complement activation. Relationship between immune complex levels, state of C3, and numbers of receptors for C3b. AB - C3-bearing immune complexes and C3 activation products were detected by using two monoclonal antibodies, one specific for a neoantigenic determinant on C3c and the other for C3d. To quantitate immune complexes, the anti-C3c or anti-C3d antibodies were fixed to microtiter plates and reacted with test plasma. The binding of C3-bearing immune complexes in this plasma was then measured with radioisotope- or enzyme-labeled anti-human IgG. To test for C3 breakdown products, solid-phase monoclonal antibody to the C3d neoantigen was reacted with EDTA-plasma samples, and fixed iC3b or C3d was measured with a polyclonal anti-C3 antibody. Patients with autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and Sjogren's syndrome, and paracoccidioidomycosis were found to contain immune complexes bearing C3b/iC3b or C3d. In most conditions, there were more C3d-containing immune complexes than C3b/iC3b. Although CR1 (C3b receptors) rapidly converted immune complex-bound iC3b to C3dg/C3d and lupus patients had reduced CR1, no correlation between the state of C3 on circulating immune complexes or levels of immune complexes and CR1 numbers was seen. However, levels of C3-fixing ICs correlated with levels of C3 activation products. This assay system with monoclonal antibodies to neoantigens expressed on activated, but not native, C3 provides sensitive and specific means for detecting and classifying C3-fixing immune complexes and for assessing C3 activation. PMID- 2932467 TI - Allogeneic suppressive effects of pregnancy sera on monocytes of responding cells in human mixed lymphocyte reactions. AB - The purified human monocytes of a responding donor preincubated with heat inactivated serum T1264 or T1295 derived from pregnant women for 30 min at 37 degrees C expressed allogeneic suppressive effects on the proliferative response of the lymphocytes from the same donor in the allogeneic mixed lymphocyte reaction (MLR). The pregnancy serum in our experiments was found not to contain any antibodies to DR and DQ antigens on monocytes of the responding donor. Accordingly, the suppressive effects mediated by monocytes were not based on the blocking of DR and DQ antigens on monocytes of the responding donor by DR and DQ antibodies in the serum. These highly reproducible allogeneic suppressive effects by monocytes of the responding donor were demonstrated in the MLR specific for DRw9-positive stimulating cells, whereas no inhibition was seen in the cultures with other stimulating cells of different DR phenotypes. Additionally, these suppressive effects appeared on the monocytes of a DR2-positive responding donor, but not on the monocytes of a DR2-negative responding donor. These suppressive effects were abolished when the absorbed pregnancy serum by monocytes of the DR2 positive responding donor was used. In this suppression phenomenon that we discovered, monocytes of the responding donor appear to act as regulatory cells on the proliferative response of the allogeneic MLR. This regulatory function of monocytes could be expressed through the specific molecules distinct from DR and DQ determinants on monocytes in cooperation with antibodies (IgG class) in the pregnancy serum. PMID- 2932468 TI - Substructure of human von Willebrand factor. AB - Using electron microscopy, we have visualized the substructure of human von Willebrand factor (vWf) purified by two different approaches. vWf multimers, which appear as flexible strands varying in length up to 2 micron, consist of dimeric units (protomers) polymerized linearly in an end-to-end fashion through disulfide bonds. Examination of small multimers (e.g., one-mers, two-mers, and three-mers) suggests that each protomer consists of two large globular end domains (22 X 6.5 nm) connected to a small central node (6.4 X 3.4 nm) by two flexible rod domains each approximately 34 nm long and approximately 2 nm in diameter. The protomer is 120 nm in length when fully extended. These same structural features are seen both in vWf molecules that were rapidly purified from fresh plasma by a new two-step procedure and in those purified from lyophilized intermediate-purity Factor VIII/vWf concentrates. The 240,000-mol wt subunit observed by gel electrophoresis upon complete reduction of vWf apparently contains both a rod domain and a globular domain and corresponds to one half of the protomer. Two subunits are disulfide-linked, probably near their carboxyl termini, to form the protomer; disulfide bonds in the amino-terminal globular ends link promoters to form vWf multimers. The vWf multimer strands have at least two morphologically distinct types of ends, which may result from proteolytic cleavage in the globular domains after formation of large linear polymers. In addition to releasing fragments that were similar in size and shape to the repeating protomeric unit, plasmic degradation of either preparation of vWf reduced the size of multimers, but had no detectable effect on the substructure of internal protomers. PMID- 2932469 TI - Von Willebrand's disease with spontaneous platelet aggregation induced by an abnormal plasma von Willebrand factor. AB - We have investigated and characterized the abnormalities in four unrelated patients with von Willebrand's disease (vWd) who have (a) enhanced ristocetin induced platelet aggregation (RIPA) at low ristocetin concentrations, (b) absence of the largest plasma von Willebrand factor (vWf) multimers, and (c) thrombocytopenia. The platelet-rich plasma of these patients aggregates spontaneously without the addition of any agonists. When isolated normal platelets are resuspended in patient plasma spontaneous aggregation occurs; however, the patients' plasmas did not induce platelet aggregation of normal washed formalinized platelets. When the patients' platelets are suspended in normal plasma, spontaneous aggregation is not observed. The spontaneous platelet aggregation (SPA) is associated with dense granule secretion as measured by ATP release and alpha granule release as measured by beta-thromboglobulin and platelet factor 4 release. The SPA is totally inhibited by 5 mM EDTA, prostaglandin I2, and dibutryl cyclic AMP, while it is only partially inhibited by 1 mM EDTA, acetylsalicylic acid, or apyrase. A monoclonal antibody directed against glycoprotein Ib (GPIb) and/or a monoclonal antibody against the glycoprotein IIb/IIIa (GPIIb/IIIa) complex totally inhibits the SPA. The vWf was isolated from the plasma of one of these patients. The purified vWf induced platelet aggregation of normal platelets resuspended in either normal or severe vWd plasma, but the vWf did not induce platelet aggregation of normal platelets resuspended in afibrinognemic plasma. Sialic acid and galactose quantification of the patient's vWf revealed approximately a 50% reduction compared with normal vWf. These studies indicate that a form of vWd exists, which is characterized by SPA that is induced by the abnormal plasma vWf. The SPA is dependent on the presence of plasma fibrinogen, and the availability of the GPIb and the GPIIb/IIIa complex. In this variant form of vWd the abnormal vWf causes enhanced RIPA, SPA, and thrombocytopenia. PMID- 2932470 TI - Linkage of a membrane skeleton to integral membrane glycoproteins in human platelets. Identification of one of the glycoproteins as glycoprotein Ib. AB - Experiments were performed to determine whether platelets contain a membrane skeleton. Platelets were labeled by a sodium periodate/sodium [3H]borohydride method and lysed with Triton X-100. Much of the filamentous actin could be sedimented at low g forces (15,600 g, 4 min), but some of the actin filaments required high-speed centrifugation for their sedimentation (100,000 g, 3 h). The latter filaments differed from those in the low-speed pellet in that they could not be depolymerized by Ca2+ and could not be sedimented at low g forces even from Triton X-100 lysates of platelets that had been activated with thrombin. Actin-binding protein sedimented with both types of filaments, but 3H-labeled membrane glycoproteins were recovered mainly with the high-speed filaments. The primary 3H-labeled glycoprotein recovered with this "membrane skeleton" was glycoprotein (GP) Ib. Approximately 70% of the platelet GP Ib was present in this skeleton. Several other minor glycoproteins, including greater than 50% of the GP Ia and small amounts of three unidentified glycoproteins of Mr greater than 200,000, were also recovered with the membrane skeleton. The Triton X-100 insolubility of GP Ib, GP Ia, a minor membrane glycoprotein of 250,000 Mr, and actin-binding protein resulted from their association with actin filaments as they were rendered Triton X-100-soluble when actin filaments were depolymerized with deoxyribonuclease I and co-isolated with actin filaments on sucrose gradients. When isolated platelet plasma membranes were extracted with Triton X 100, actin, actin-binding protein, and GP Ib were recovered as the Triton X-100 residue. These studies show that unstimulated platelets contain a membrane skeleton composed of actin filaments and actin-binding protein that is distinct from the rest of the cytoskeleton and is attached to GP Ib, GP Ia, and a minor glycoprotein of 250,000 Mr on the plasma membrane. PMID- 2932471 TI - Plasma levels of immunoreactive atrial natriuretic factor in healthy subjects and in patients with edema. AB - Atrial natriuretic factor (ANF), a recently sequenced cardiac peptide, has been shown to have potent natriuretic, diuretic, and vasodilating effects in several species. We have developed a radioimmunoassay to measure the levels of immunoreactive ANF in human plasma. Plasma levels of ANF in healthy volunteers on a low sodium diet were 9.8 +/- 1.4 pmol/liter and increased to 21.9 +/- 3.0 on a high sodium diet. The levels of atrial natriuretic factor correlated directly with urinary sodium and inversely with plasma renin activity and plasma aldosterone levels. Patients with marked edema due to congestive heart failure had plasma levels of atrial natriuretic factor five times higher than normal (P less than 0.05), whereas patients with cirrhosis and edema had levels that were not different from normal. These results suggest that atrial natriuretic factor plays an important role in the adaptation to increased sodium intake. PMID- 2932472 TI - Atrial natriuretic factor in human blood. AB - To determine whether atrial natriuretic factor (ANF) is a circulating hormone in men, a radioimmunoassay suitable for the estimation of ANF in human plasma was developed and the nature of plasma ANF was characterized. Plasma ANF was extracted before radioimmunoassay by affinity chromatography on a column of ANF antibody-coupled agarose. When plasma ANF extract was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, with the radioimmunoassay of the eluted gel slices for ANF, almost all of the ANF activities ran in the 3,000-mol wt area, while three peaks of ANF were observed in human atrial tissue extract, molecular weights of which corresponded to 14,000, 6,000, and 3,000, respectively. Reversed-phase high performance liquid chromatography of atrial tissue extract resolved multiple forms of ANF. In contrast, one major peak was observed in human plasma extract, and its retention time coincided with that of synthetic human alpha-atrial natriuretic polypeptide. When 500 ml of 0.9% saline was infused into six healthy subjects over 45 min, plasma levels of ANF were unequivocally elevated. The mean plasma ANF concentrations rose from the baseline (23.0 +/- 2.5 pg/ml, mean +/- SEM, n = 6) to the peak (41.8 +/- 4.9 pg/ml, mean +/- SEM) at 75 min postinfusion. No significant change in plasma ANF, on the other hand, was found in the control group. These results suggest that ANF is a circulating hormone in men and is secreted in response to isotonic volume expansion. PMID- 2932473 TI - Membrane markers, target cell specificity, and sensitivity to biological response modifiers distinguish human natural cytotoxic from human natural killer cells. AB - In the present report, we provide evidence for the distinct existence of a human natural cytotoxic (HNC) cell. This HNC cell can be identified by the monoclonal antibody HNC-1A3 and by the absence of the T10 antigen, other antigenic markers being shared, at least in part, with natural killer (NK) cells, T cells, or monocytes. In addition, the HNC cell preferentially kills the MA-160 target, the herpes simplex virus-1-infected MA-160 cell line, and the two human tumor cell lines HEp-2 and HF-2. It has weak lytic activity against the NK-sensitive K562 cell line or its relatively NK-resistant clone I subline. The cytotoxic activity of the HNC cell is not augmented by interferon but is markedly enhanced by interleukin 2 and by a measles-virus-induced factor (MVF). Furthermore, it is not inhibited by cyclosporin A (CsA), in contrast to NK cell cytotoxicity against the K562 target cell line which is augmented by interferon, inhibited by CsA, and not affected by MVF. These data suggest that spontaneously cytotoxic cells may belong to more than one subset of human lymphocytes, and that HNC cells may be defined in man using membrane markers, target cell specificity, and sensitivity to biological response modifiers. PMID- 2932475 TI - Recombinant DNA studies on stored necropsy brain samples from patients with Huntington's chorea. AB - An analysis of deoxyribonucleic acid (DNA) in deep frozen brain samples taken from 100 patients with Huntington's chorea after death showed undegraded DNA in 44 cases. Of these, 16 were analysed with G8, a recombinant DNA probe, linked to the Huntington's chorea locus. In all cases unambiguous Southern blots were obtainable. No correlation between the yield of DNA and the principal storage factors was observed. The use of stored brain tissue obtained after death from patients with Huntington's chorea should be considered when analysis of DNA is needed for predictive studies, but DNA should preferably be isolated from the tissue before storage as degradation in these samples can occur. PMID- 2932474 TI - Immunoglobulin G is a platelet alpha granule-secreted protein. AB - It has been known for 27 yr that blood platelets contain IgG, yet its subcellular location and significance have never been clearly determined. In these studies, the location of IgG within human platelets was investigated by immunocytochemical techniques and by the response of platelet IgG to agents that cause platelet secretion. Using frozen thin-sections of platelets and an immunogold probe, IgG was located within the alpha-granules. Thrombin stimulation caused parallel secretion of platelet IgG and two known alpha-granule proteins, platelet factor 4 and beta-thromboglobulin, beginning at 0.02 U/ml and reaching 100% at 0.5 U/ml. Thrombin-induced secretion of all three proteins was inhibited by prostaglandin E1 and dibutyryl-cyclic AMP. Calcium ionophore A23187 also caused parallel secretion of all three proteins, whereas ADP caused virtually no secretion of any of the three. From these data and a review of the literature, we hypothesize that plasma IgG is taken up by megakaryocytes and delivered to the alpha-granules, where it is stored for later secretion by mature platelets. PMID- 2932476 TI - Effects of ketanserin, a 5-HT2-receptor antagonist, on the blood flow response to temperature changes in the diabetic foot. AB - We studied the effect of ketanserin, a relatively specific antagonist for 5 hydroxytryptamine2-serotonergic receptors, on the total blood flow to the foot of patients with diabetes using a computerized pulse volume plethysmograph and a temperature controlled foot chamber. Ketanserin was administered intravenously as a bolus of 10 mg over four minutes followed by a constant infusion at the rate of 5 mg/hr. Saline infusion served as a control in each subject. Sixteen patients with type II diabetes and two patients with type I diabetes were studied. Mean age was 58.5 +/- 1.6 years and mean duration of diabetes was 10 +/- 2 years. Basal blood flow (mean +/- SEM, mL/100 mL/min) at room temperature was 3.77 +/- 0.99 with saline and 12.07 +/- 1.81 with ketanserin. At 38 to 40 degrees C, the values were 4.84 +/- 1.09 and 16.93 +/- 1.83. Reactive hyperemia was measured following three minutes of arterial occlusion; at 38 to 40 degrees C the flow rate was 20.67 +/- 2.45 with saline and 30.86 +/- 3.02 with ketanserin, while at 8 to 10 degrees C the corresponding values were 15.63 +/- 2.01 and 27.16 +/- 2.03. All differences between saline and ketanserin had a P less than .01. Venous distensibility (vol% at 50 mm Hg) at 8 to 10 degrees C was 0.55 +/- 0.05 with saline and 0.90 +/- 0.15 with ketanserin, P less than .05. Our findings are consistent with the hypothesis that serotonin is involved in the limitation of blood flow to the foot in diabetes and that ketanserin may play a potential role in therapy. PMID- 2932477 TI - Trigeminal mesencephalic neurons innervating functionally identified muscle spindles and involved in the monosynaptic stretch reflex of the lateral pterygoid muscle of the guinea pig. AB - Location of the neurons in the trigeminal mesencephalic nucleus innervating stretch receptors of the lateral pterygoid muscle and the mode of their synaptic connection on the lateral pterygoid motoneurons of the guinea pig were studied physiologically as well as morphologically, in comparison with the trigeminal mesencephalic neurons innervating muscle spindles in the superficial masseter muscle, with the following results: stimulation of the caudal half of the trigeminal mesencephalic nucleus evoked monosynaptic excitatory postsynaptic potentials in the ipsilateral lateral pterygoid motoneurons. Stimulation of the lateral pterygoid nerve directly evoked spike potentials in the neurons located in the caudal half of the ipsilateral trigeminal mesencephalic nucleus, which responded with increased firing to stretch, and with silent period to twitch, of the ipsilateral lateral pterygoid muscle. Averaging of intracellular potentials of the lateral pterygoid motoneurons with extracellular spike potentials of these trigeminal mesencephalic neurons revealed excitatory postsynaptic potentials after a monosynaptic latency, but no inhibitory postsynaptic potentials. Injection of horseradish peroxidase into the lateral pterygoid muscle labeled 15 20 cells in the caudal half of the ipsilateral trigeminal mesencephalic nucleus, while 174-228 cells retrogradely labeled by horseradish peroxidase were found throughout the whole rostrocaudal extent of the ipsilateral trigeminal mesencephalic nucleus following injection of horseradish peroxidase into the masseter muscle. It was concluded that neurons in the caudal half of the trigeminal mesencephalic nucleus send their peripheral processes to stretch receptors, presumably muscle spindles, in the ipsilateral lateral pterygoid muscle and that their central processes have excitatory synapses on ipsilateral lateral pterygoid motoneurons, thus comprising the afferent limb of a monosynaptic stretch reflex arc of the lateral pterygoid muscle of the guinea pig. PMID- 2932478 TI - Bullous lichen planus after intravenous pyelography. PMID- 2932479 TI - Oral ibuprofen and minocycline for the treatment of resistant acne vulgaris. PMID- 2932481 TI - Psoriasiform and related papulosquamous disorders. PMID- 2932480 TI - Cardiac gated MR imaging of cerebrospinal fluid flow. AB - This is a preliminary investigation of the cerebrospinal fluid (CSF) spaces using cardiac gated magnetic resonance imaging. A variation of intensity of the signal from the cerebral aqueduct is demonstrated during the cardiac cycle. The pattern of this variation suggests pulsatile CSF flow. Calculations that have been verified by phantom measurements show that CSF flow rates less than 1 mm/s may be detectable. Magnetic resonance may therefore offer a new method for the demonstration and measurement of CSF flow. PMID- 2932482 TI - The dexamethasone suppression test in depressive, non-depressive and schizoaffective psychosis. AB - The authors examined the 24-h plasma cortisol response to dexamethasone in 19 patients with co-existing depressive and psychotic features and in 12 non depressed patients with only psychotic features. The rate and degree of abnormal dexamethasone suppression was greatest in patients who met RDC criteria for primary depressive disorder. Patients who met criteria for schizoaffective- mainly schizophrenic--depressed and other psychotic disorders did not differ from each other in their response to dexamethasone. These data suggest that the DST may have utility in the diagnostic evaluation of some patients with depressive and psychotic features. PMID- 2932484 TI - Dexamethasone suppression test and sleep deprivation in endogenous depression. AB - The dexamethasone suppression test (DST) was carried out in 24 endogenously depressed and 15 non-endogenously depressed patients before and on the day after therapeutic sleep deprivation (SD) for one night. The diagnostic selectivity of DST results was not improved by combination with SD. The alteration of DST cortisol levels after SD, irrespective of the direction of change (so-called cortisol response) was significantly higher in endogenous depressives than in neurotic depressives. No unequivocal statement was possible on (a) the predictive value of DST data for the SD effect and (b) the relationship between neuroendocrine changes and the antidepressive effect of SD. PMID- 2932483 TI - Lithium and impairment of renal concentrating ability. AB - In 19 patients on lithium maintenance therapy, impairment of renal concentrating ability was found to correlate with daily lithium dose. The correlation between dose and impaired renal concentrating ability was strongest for patients on regular lithium preparations and not significant for patients on a slow release preparation. In 2 patients with severe polyuria, renal concentrating ability increased markedly with thiazide treatment. No relationship between lithium dosing parameters and other side effects was found. These results emphasize the importance of dose and type of preparation of lithium in the production of renal side effects. PMID- 2932485 TI - The treatment of depression in patients with epilepsy. A double-blind trial. AB - Forty-two patients with depression and epilepsy were entered into an antidepressant trial of amitriptyline, nomifensine and placebo. The dose of the active drug was 25 mg tid, which was doubled in non-responders on the active drug after 6 weeks. At that point a further 6 week follow-up was carried out. Serum antidepressant and anticonvulsant levels were assessed. The results indicated that at 6 weeks all patients showed a decline in their depression scores but at 12 weeks nomifensine was superior to amitriptyline. The possible reasons for this and the clinical implications of this are discussed. PMID- 2932486 TI - Attempts to attenuate the 'cheese effect'. Combined drug therapy in depressive illness. AB - Although earlier results, employing intravenous tyramine challenge, had indicated that a tricyclic antidepressant plus monoamine oxidase inhibitor drug combination might be free from the 'cheese effect', the experiments reported here, involving oral tyramine challenge during the combined therapy, showed that relaxation of a tyramine-free diet during such a drug regimen might be unsafe. Preliminary observations indicated that combined (-)-deprenyl plus nonselective monoamine oxidase inhibitor therapy might lead to an unacceptable degree of orthostatic hypotension without reduction in tyramine sensitivity. PMID- 2932487 TI - Life events in depression. Relationship to subtypes. AB - Life events that had occurred in the 6 months before the onset of depression were recorded in 40 depressed patients and 41 normal controls. The depressed patients had experienced significantly more life events and significantly more undesirable life events than the controls. The 20 patients with a DSM-III diagnosed major depressive episode (MDE) without melancholia had experienced significantly more life events in the 6 months before the onset of depression than the 20 patients with a major depressive episode with melancholia. The patients with MDE without melancholia, but not the MDE with melancholia patients, had also experienced significantly more life events than a group of age- and sex-matched normal controls. PMID- 2932488 TI - Outcome with desipramine therapy in subtypes of nonpsychotic major depression. AB - A consecutive series of 42 outpatients with major depression were classified as having endogenous or nonendogenous depression according to RDC, primary or secondary depression according to the criteria of Feighner et al. (1972) and suppression or nonsuppression according to a dexamethasone suppression test. These groups were then compared according to outcome after an initial placebo phase and after 6 weeks of treatment with desipramine. Patients with secondary depression were somewhat more likely to respond to placebo and were significantly less likely to complete the entire course of treatment. The primary/secondary distinction but not the endogenous/nonendogenous distinction predicted clinical status after desipramine therapy. In accord with earlier reports, nonsuppressors faired better than suppressors though this difference did not reach statistical significance. Moreover, nonsuppressors tended to have outcomes which were more discrete as reflected in a bimodal distribution for final scores, in contrast, final scores for suppressors assumed a more unimodal distribution. PMID- 2932489 TI - Genetic and environmental factors in major depression. AB - A study of 48 individuals with major depression in a sample of 443 adoptees has shown that depression is positively but not significantly correlated with a biologic background of affective disorder. Both primary and secondary depression was positively and significantly correlated with several environmental factors. In males, an adoptive home where another individual had an alcohol problem increased depression; in females, death of an adoptive parent prior to adoptee age 19 and an adoptive family where another individual had a behavior disturbance increased depression. Results suggest that the environmental factors occurring prior to adoptees age 18 predisposed to depression. PMID- 2932490 TI - High fatality rates of late-life depression associated with cardiovascular disease. AB - Sixty-two elderly depressives were located one year after discharge. Eight patients (13%) had died, 2.6 times higher than the expected mortality rate. Patients dying were more likely to have had a diagnosis of cardiovascular disease (P less than 0.001). PMID- 2932491 TI - Depression, cortisol metabolism and lymphocytopenia. AB - Depression is often associated with hypercortisolemia. Because high levels of cortisol influence the distribution of different types of leukocytes in the blood stream, we examined the percentages and absolute numbers of circulating neutrophils and lymphocytes in 29 depressed patients who were nonsuppressors on the Dexamethasone Suppression Test (DST), 28 depressed patients who were suppressors on the DST, and 52 schizophrenic controls. We found no significant differences in either RBC or WBC counts in the 3 groups. There were, however, significant differences in the percentages of both neutrophils and lymphocytes as well as the absolute number of lymphocytes among the groups. These differences were mostly due to significantly lower lymphocyte percentages and absolute counts in the depression-nonsuppressor group. We also found a significant negative association between post-dexamethasone plasma cortisol concentrations and blood lymphocyte counts. These data suggest a close interaction between cortisol metabolism and lymphocyte regulation in major depression. PMID- 2932492 TI - Differentiation of psychotic from nonpsychotic depression by a biological marker. AB - In a study of fasting plasma serine levels (PSL) previously shown to be a biological marker for psychosis, we found significantly higher (P = 0.0008) PSL in 18 psychotic depressives when compared to 22 nonpsychotic depressives. Similarly the activity of the enzyme serine hydroxymethyltransferase (SHMT) which cleaves serine to glycine, was significantly lower (P less than 0.0001) in psychotics than in nonpsychotics. The difference between psychotic and nonpsychotic depressives were not attributable to age, sex or drug intake. This finding is in support of the hypothesis that these two types of depressions are qualitatively distinct from each other. PMID- 2932493 TI - The categorical and dimensional models of endogenous depression. AB - We calculated a Research Diagnostic Criteria (RDC) endogenous score for 257 depressed inpatients based on the number of endogenous criteria present. The distribution of RDC endogenous scores was unimodal. There was no association between endogenous scores and results of the Dexamethasone Suppression Test, or morbid risk for depression in the patients' first-degree relatives. The morbid risk for a family history of alcoholism tended to decrease with increasing endogenous scores, although a consistent steady decline was not observed. The results suggest that the RDC criteria do not fit either the categorical or dimensional model of endogenous classification. Potential sources of difficulty with the RDC endogenous criteria are discussed. PMID- 2932494 TI - Blood levels of vanadium, caesium, and other elements in depressive patients. AB - Levels of vanadium and 29 other elements were measured in whole blood of 25 depressive patients, 13 recovered depressive, and 24 control subjects. Vanadium levels were normal in depressive patients, and did not change on recovery. Changes of doubtful significance were found in blood levels of copper, strontium and chromium on recovery from depressive illness. The depressive patients had reduced blood levels of caesium which increased towards normal on recovery. This finding is discussed in relation to pertinent neurochemical and behavioural effects of caesium. PMID- 2932495 TI - Reported weight loss and dexamethasone nonsuppression in depressed patients. A negative study. AB - In a sample of 96 patients with DSM-III major depressive disorder and in a subset of 78 melancholic patients, there was no evidence that dexamethasone nonsuppression was more common in patients with reported weight loss. PMID- 2932496 TI - Sexuality and the disabled: apathy on the campus. PMID- 2932497 TI - Timepieces. Continuum. PMID- 2932498 TI - The effect of corticosteroids on monocyte and neutrophil activation in bronchial asthma. AB - The expression of IgG (Fc) receptor (FcR) and complement receptor (CR) on peripheral blood monocytes and neutrophils was determined by the rosette technique in patients with asthma receiving different forms of treatment. In 31 patients taking inhaled therapy (i.e., bronchodilators alone or in combination with inhaled corticosteroids), monocyte FcR (48.19 +/- 1.24%, mean +/- SEM) and complement (66.54 +/- 1.09%) rosettes were significantly higher (FcR p less than 0.001, CR p less than 0.001) than in the 17 healthy, normal control subjects (FcR 37.94 +/- 0.82%, CR 59.7 +/- 0.98%). These increases in the percent rosettes between the two groups were observed even when a wide concentration range of IgG or complement was used to coat the red cells. No significant differences in monocyte receptor expression were observed between those patients being treated with bronchodilators alone or patients being treated in combination with inhaled corticosteroids. In 19 patients with asthma receiving oral corticosteroids, the mean monocyte FcR (38.21 +/- 1.73%) and CR (52.78 +/- 2.09%) were significantly reduced when these patients were compared with those patients receiving inhaled therapy alone (FcR p less than 0.001, CR p less than 0.001), and there was a significant inverse correlation between the percent rosettes and the dose of prednisolone. Neutrophil CR (51.32 +/- 1.30%, p less than 0.05) but not FcR expression (24.7 +/- 0.80%) was significantly increased when these were compared with those of control subjects (FcR 24.7 +/- 0.60%, CR 47.11 +/- 0.86%), and both neutrophil FcR and CR expression was significantly reduced (FcR p less than 0.01, CR p less than 0.001) in those patients with asthma receiving oral corticosteroids. (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2932499 TI - Role of interleukin-2 in the age-related impairment of immune function. PMID- 2932500 TI - Craniofacial dysmorphology in syndromes associated with abnormal physical growth. AB - Nine syndromes associated with varying patterns of abnormal physical growth were selected to study quantitative craniofacial dysmorphology with cephalometric analysis. A schematic diagram was developed in which a hexagon measures the neurocranium and facial skeletal size and form. This hexagon offers the possibility of quantitative dysmorphic roentgencephalometry to study the effects of various growth disorders on the craniofacial complex. PMID- 2932501 TI - Treatment of liver cirrhosis with microsomal enzyme-inducing compound in the rat. AB - The effect of therapy with a microsomal enzyme-inducing drug on the cirrhotic liver in male Wistar rats was investigated by morphological and biochemical means. The cirrhotic animals were treated with medroxyprogesterone acetate (MPA) 100 mg/kg body wt, i.p. daily for a week. In the cirrhotic rats liver weight was enhanced, liver protein content was increased while total liver DNA content remained unchanged upon MPA treatment. The hepatic regenerative nodule size increased, as determined by morphological means. Hepatic microsomal metabolic activity was improved, as seen by increases in NADPH-cytochrome P-450 reductase and aminopyrine N-demethylase activities and cytochrome P-450 content. Since the increases in liver protein content and metabolic activity were relatively greater in the cirrhotic than intact animals upon MPA treatment, it was suggested that the spontaneous regeneration associated with liver cirrhosis may affect the induction phenomenon. The results demonstrate that an enzyme inducer may have beneficial effects on the cirrhotic liver by elevating metabolic activity and parenchymal mass. PMID- 2932502 TI - Skin diseases: current concepts, therapy. 4. Fungus infections. PMID- 2932503 TI - CPH-86, a highly purified podophyllotoxin, efficiently suppresses in vivo and in vitro immune responses. AB - Podophyllotoxin, a component of the plant resin Podophyllin, has been used as a clinical drug for many years. Recently it has been highly purified under the denomination of CPH-86. We here demonstrate that extremely low doses of the compound efficiently inhibit antibody responses to SRBC and prolong allogeneic skin graft survival in mice. In vitro immune reactions, such as mitogen and alloantigen induced proliferation and development of cytotoxic T cells, are also suppressed in a dose dependent manner. This effect does not seem to be due to direct cellular toxicity or to a shift in the kinetic pattern of the responses. PMID- 2932504 TI - Plantar hyperkeratosis: a study of callosities and normal plantar skin. AB - Although callosities of the plantar skin are common and often disabling, little is known of their pathology or the reasons for their persistence. In this study plantar epidermal structure and cell renewal were investigated in patients with callosities and normal, age-, sex- and site-matched control subjects. Tritiated thymidine autoradiographic labeling indices were increased in the calluses but the dansyl chloride fluorescence clearance time was prolonged, reflecting the increased thickness of the stratum corneum. The number of corneocytes that could be removed from the surface of callosities by a standardized stimulus was considerably increased compared to controls but after adhesive tape stripping no such increase was observed. The density of corneocytes as measured on Percoll gradients was decreased in corneocytes from callus compared to normal plantar skin, and their volume was increased. These observations suggest that there are differences in epidermal differentiation due to an increased rate of epidermal cell production in plantar skin affected by callosity. PMID- 2932505 TI - Binding of unglycosylated and glycosylated human recombinant interferon-gamma to cellular receptors. AB - Recombinant human interferons (IFNs), either unglycosylated produced in E. coli (rIFN-gamma) or glycosylated produced in CHO cells (g-rIFN-gamma), were labeled with 125I to similar specific activities to study their interaction with cell surface receptors. When analyzed by gel electrophoresis, rIFN-gamma run as a single polypeptide of Mr 15,000-17,000, whereas g-rIFN-gamma separated into three components of Mr 20,000, 22,000, and 43,000, which corresponded to the known size of the two monomeric and one dimeric forms of glycosylated natural IFN-gamma. The binding of the two species of 125I-IFN-gamma was competed equally by rIFN-gamma in competition displacement experiments with Daudi cells, indicating that these IFNs bind with similar high affinity to the same receptors. KD values of 1.25 X 10(-10) and 2.5 X 10(-10) M were determined for g-rIFN-gamma and rIFN-gamma, respectively. This relatively small difference in KD does not apparently result in a detectable difference in biological activity, as measured by the increase in 2',5'-oligo(A) synthetase activity in IFN-treated HeLa and A549 cells. These results indicate that glycosylation of IFN-gamma does not play a significant role in its interaction with cellular receptors and in the induction of a biological response. PMID- 2932506 TI - [Surgical treatment of subacute infective endocarditis in a patient with polyuric renal failure due to immune complex glomerulonephritis: a case report]. PMID- 2932507 TI - [Studies on the electromyogram of the maternal abdominal surface--the significance and the clinical application]. AB - The study made me recognize the significance of the electromyogram of the maternal abdominal surface (MAS-EMG), which is taken in a non-invasive and by a non-biding procedure, and also it has been proven that I can get practical and objective information from the MAS-EMG during labor in 40 primiparous and 50 multiparous. That is to say that: I can record the MAS-EMG by using the right filters [low cut filter (time constant 0.003s), high cut filter (150 Hz), notch filter (50 Hz)] in order to eliminate noise constituents. The MAS-EMG appears intermittently in the acceleration phase to the maximum slope phase when uterine contraction occurs and keeps the rhythmic MAS-EMG increased dynamically along with the progress of delivery. the available frequency zone in the MAS-EMG is from 10 Hz to 110 Hz, information which I obtained during delivery. The characteristic of the amplitude in the MAS-EMG is that the left side is larger than the right side-especially the left m. externus abdominus shows a high electrical potential. The following order of MAS-EMG occurred frequently: left m. obliquus externus abdominus----left m. obliquus internus abdominus----left m. transversus abdominus and right m. obliquus externus. The peak-hold curve of the MAS-EMG shows a great difference between normal delivery and abnormal delivery patterns. The wave forms for amplitude in the MAS-EMG constitute a practical body of information for the evaluation of involuntary and reflective bearing down action during delivery. PMID- 2932509 TI - [Experimental study of oral administration of streptococcal preparation "OK-432". The 6th report: its effect on in vivo anti-tumor immunity of the mice with transplanted cecal tumor]. PMID- 2932508 TI - Steroid concentrations in human cervical tissue in relation to cervical ripening. AB - Steroid concentrations in human cervical tissue were measured in order to study the mechanism of cervical ripening at term. Thirty-four women at 37 to 41 weeks of gestation were selected for the study and divided into two groups. Group A consisted of 21 cases with ripened cervix, and Group B consisted of 13 cases with non-ripened cervix. The condition of the cervix was judged by the Bishop's Score. Free and conjugated estrone (E1), estradiol (E2), estriol (E3), and dehydroepiandrosterone (DHA) concentrations in cervical tissue were measured by radioimmunoassay (RIA). Significantly higher concentrations of free E1, conjugated E2, E3 and DHA were found in Group A than in Group B. Cervical tissue during labor showed a further increase in the concentrations of these steroids. Pronounced increases of the steroid concentrations were noted following DHA Sulfate (DHA-S) administration. These results suggest an intimate relationship between cervical ripening and steroid concentrations in cervical tissue during pregnancy. PMID- 2932510 TI - Heterotopic pregnancy from in vitro fertilization. AB - A case of heterotopic or combined intrauterine and tubal ectopic pregnancy is described following in vitro fertilization and the transfer of five four-cell embryos. The phenomenon is known to be related to ovarian stimulation by gonadotropin therapy, and there is an increased risk with underlying tubal disease. This patient had both variables. Techniques applied at the time of embryo transfer are also implicated, namely, the use of culture medium with 50% maternal serum to convey the embryos to the uterus, the catheterization method, and the position of the patient during transfer. PMID- 2932511 TI - A program for in vitro fertilization and embryo transfer at the Southern California Fertility Institute, Inc. PMID- 2932512 TI - [The relation between salivary IgA concentration and dental caries incidence in Mongoloid children]. PMID- 2932513 TI - Serial changes in humoral and cellular immunity induced by prostaglandin E2 treatment of murine immune complex glomerulonephritis. AB - To examine the mechanism by which prostaglandin E2 (PGE2) inhibits the development of apoferritin (HAF)-induced immune complex glomerulonephritis (ICGN), weekly determinations of glomerular histologic conditions, blood urea nitrogen (BUN), total immunoglobulin levels, anti-HAF antibody, peripheral blood and splenic T cell subsets, and splenic suppressor cell activity were compared between mice receiving HAF and mice additionally treated with PGE2. PGE2 therapy prevented the development of glomerular hypercellularity and the increase in BUN concentration. Administration of PGE2 reduced anti-HAF IgG levels, but total IgM and IgG1, IgG2a, and IgG2b levels were unchanged. Mice receiving HAF alone demonstrated serial reductions in phenotypically identified peripheral blood pan T cells and suppressor-cytotoxic T cells. PGE2-treated mice maintained normal levels of peripheral blood T cell subsets. Significant reductions in splenic total T cells and suppressor-cytotoxic cells occurred in mice receiving HAF as compared with normal mice. This reduction was offset by an increase in splenic B cells. PGE2 therapy prevented the decrease in splenic T cells at week 1, but not at week 4. Nonspecific suppressor cell activity, as measured by the ability of spleen cells from experimental mice to suppress a mixed lymphocyte reaction (MLR) or to suppress MLR-induced polyclonal IgG synthesis, was not different between the two groups. We conclude that prevention of HAF-ICGN by PGE2 is associated with a reduction in nephritogenic antibody production without an alteration in total immunoglobulin synthesis or the generation of nonspecific suppressor T cells. Changes in the percent of peripheral blood and splenic T cells and B cells may represent an effect of PGE2 on antigen-stimulated B cell proliferation. PMID- 2932515 TI - Myoelectric paraspinal response to spinal loads: potential for monitoring low back pain. AB - LBP evaluation has been hampered by the subjectivity of available clinical procedures and the paucity of factual information about spinal dysfunction. Objective indices of spinal pathomechanics would assist the clinician to prescribe and evaluate appropriate treatment. This project assesses paraspinal myoelectric symmetry as a potential objective measure of low back performance. A preliminary group (N = 39) of symptomatic subjects was prospectively tested to choose parameters for the blinded experiment to follow. The experimental group of volunteers (N = 37) were electromyographically monitored while the subjects performed selected postural tasks which did not produce pain. Results were compared to orthopedic tests and history. Four arbitrary myoelectric classifications were defined for subject grouping and comparison: subjects with symmetrical paraspinal task performance, occasional (less than 4 tasks) asymmetry, low amplitude response for quasi-static loads, and large amplitude asymmetry (greater than 4 tasks). Eighty percent of subjects with significant asymmetry of muscle action had recent LBP history. Isolated task testing is inconclusive as a clinical parameter. However, observation of performance of a series of tasks may be useful in clinical diagnosis and monitoring of function in low back pain. PMID- 2932514 TI - Thromboxane A2 and prostacyclin do not modulate the systemic hemodynamic response to cold in humans. AB - The immersion of a limb in a mixture of water and ice induces in normal humans an initial vasoconstriction mediated mainly by catecholamine release. In some studies the cold pressor test was associated with an increase in vasoconstrictor thromboxane A2 and in vasodilating prostacyclin. Dazoxiben hydrochloride, a thromboxane synthase inhibitor, has been reported to suppress cold-induced vasoconstriction. We compared in a double-blind, crossover, placebo-controlled study the effects of indomethacin (a cyclooxygenase inhibitor), dazoxiben hydrochloride, and BM13.177 (a novel thromboxane receptor antagonist) on the changes in cutaneous vascular resistance and arterial blood pressure induced by cold in 12 healthy volunteers. Cold challenge produced an increase in blood pressure and an initial decrease in finger blood flow, reflecting an increase in cutaneous vascular resistance. Neither effective suppression of thromboxane A2 generation or of the effects of thromboxane A2 on platelets by the three active treatments nor increase in prostacyclin generation after ingestion of dazoxiben hydrochloride modified the hemodynamic response to cold. In conclusion, thromboxane A2 and prostacyclin do not play a significant role in the modulation of the systemic hemodynamic response to cold. In addition, thromboxane receptor antagonism in normal humans does not influence basal blood pressure. PMID- 2932516 TI - Sound graphs: a numerical data analysis method for the blind. AB - A system for the creation of computer-generated sound patterns of two-dimensional line graphs is described. The objectives of the system are to provide the blind with a means of understanding line graphs in the holistic manner used by those with sight. A continuously varying pitch is used to represent motion in the x direction. To test the feasibility of using sound to represent graphs, a prototype system was developed and human factors experimenters were performed. Fourteen subjects were used to compare the tactile-graph methods normally used by the blind to these new sound graphs. It was discovered that mathematical concepts such as symmetry, monotonicity, and the slopes of lines could be determined quickly using sound. Even better performance may be expected with additional training. The flexibility, speed, cost-effectiveness, and greater measure of independence provided the blind or sight-impaired using these methods was demonstrated. PMID- 2932517 TI - Specific suppression of allograft rejection by trinitrophenyl (TNP)-induced suppressor cells in recipients treated with TNP-haptenated donor alloantigens. AB - Suppressor T cells, activated by injection of trinitrobenzene sulphonic acid in DA rats, prevented rejection of LEW kidney allografts in a donor-specific manner when adoptively transferred into syngeneic recipients along with trinitrophenyl (TNP)-haptenated LEW alloantigen. TNP-haptenated third-party alloantigen was ineffective in this system. The donor-specific suppression was dependent, too, on the haptenic portion of the chemically modified alloantigen. Hence, fluorescein isothiocyanate-donor antigen did not lead to suppression in the presence of TNP reactive suppressor cells. There is, however, some crossreaction between DNP- and TNP-haptenated alloantigens so that TNP-reactive cells and DNP-donor antigen suppressed rejection whereas DNP-reactive cells and TNP-donor antigen did not prevent graft rejection. The suppressor cells were sensitive to cyclophosphamide and radiation but were resistant to hydrocortisone. They appear to be T cells of the OX8 (suppressor/cytotoxic) phenotype since they are positive for the pan T cell antigen W3/13, are Ig negative, and do not carry the W3/25 (T helper cell) marker. However, these suppressor cells are adherent to nylon wool. They are found mainly in the spleen, are detected there within 2 d of TNBS injection, and can persist for up to 12 wk. We propose that these cells are first-order T suppressor (Ts1) cells that act in the afferent phase of the response to a renal allograft. PMID- 2932518 TI - Interactions between T helper cells and dendritic cells during the rat mixed lymphocyte reaction. AB - This paper describes the interactions between dendritic cells (DC) and T helper (Th) cells in the rat mixed lymphocyte reaction (MLR). Th blasts that are actively proliferating were generated in a 5 d primary MLR; resting Th memory cells were derived from a 10-12 d MLR. The DC were purified from thoracic duct lymph derived from rats whose mesenteric lymph nodes had been removed. The results show that DC are the major stimulators in the primary MLR and also for the restimulation of Th blasts and Th memory cells. Th blasts rapidly formed large clusters when cultured with DC but not with Ia+ macrophages or B cells. This interaction was not dependent on a major histocompatibility complex (MHC) difference between the T blasts and the DC. Con A-activated T and B blasts also formed clusters when cultured with DC. Th memory cells formed small clusters with DC, but, in a different assay in which clusters are dispersed, we detected an antigen-specific interaction between Th memory cells and DC. The monoclonal antibodies W3/25 (anti-rat CD4) and MRC OX-6 (anti-MHC class II) blocked proliferation in the primary MLR and also inhibited the restimulation of Th memory cells. However, the restimulation of Th blasts in a secondary MLR was only blocked by MRC OX-6. These results suggest that there are different requirements for the restimulation of T blasts than for the activation of primary or memory Th cells. W3/25 and MRC OX-6 did not affect the clustering of T blasts with DC but they both inhibited the antigen-specific binding of Th memory cells to DC. The data suggest that the CD4 (W3/25) antigen is involved in antigen-specific interactions between Th cells and DC. PMID- 2932519 TI - Specific unresponsiveness in rats with prolonged cardiac allograft survival after treatment with cyclosporine. Mediation of specific suppression by T helper/inducer cells. AB - DA rats grafted with major histocompatibility complex-incompatible PVG heart grafts and treated with cyclosporine (CY) for 10 d do not reject their grafts, and develop a state of specific unresponsiveness toward PVG allografts. Cells from these animals tested in an adoptive transfer assay were incapable of restoring PVG graft rejection, and capable of specifically inhibiting the capacity of adoptively transferred normal lymph node cells (LNC) to do so. They effected third party Wistar/Furth (W/F) graft rejection, however. Adoptive transfer assays with purified subpopulations of the lymphocytes that mediated this effect showed that W3/25+ T cells of the helper/inducer subclass, when injected alone, failed to restore rejection, and were also able, when injected with normal LNC or the W/25+ cells separated from them, to prevent these cells from effecting rejection. MRC OX8+ T cells of the cytotoxic/suppressor subclass, B cells, and serum from rats with long-surviving grafts all failed to inhibit the allograft responsiveness of normal LNC, and thus were not identified as mediators of the state of specific unresponsiveness. These results show that the specific unresponsiveness that develops in rats with long-surviving grafts, and which, in part at least, is responsible for prolonged graft survival, is due to an alteration in the alloreactivity of the helper/inducer subclass of T cells. These cells not only lack the capacity to initiate a rejection response against the alloantigens of the graft, but also have the ability to inhibit the capacity of normal W3/25+ cells to do so. PMID- 2932520 TI - Ideals, central tendency, and frequency of instantiation as determinants of graded structure in categories. AB - Three possible determinants of graded structure (typicality) were observed in common taxonomic categories and goal-derived categories: (1) an exemplar's similarity to ideals associated with goals its category serves; (2) an exemplar's similarity to the central tendency of its category (family resemblance); and (3) an exemplar's frequency of instantiation (people's subjective estimates of how often it is encountered as a category member). Experiment 1 found that central tendency did not predict graded structure in goal-derived categories, although it did predict graded structure in common taxonomic categories. Ideals and frequency of instantiation predicted graded structure in both category types to sizeable and equal extents. A fourth possible determinant--familiarity--did not predict typicality in either common taxonomic or goal-derived categories. Experiment 2 demonstrated that both central tendency and ideals causally determine graded structure, and work showing that frequency causally determines graded structure is discussed. Experiment 2 also demonstrated that the determinants of a particular category's graded structure can change with context. Whereas ideals may determine a category's graded structure in one context, central tendency may determine a different graded structure in another. It is proposed that graded structures do not reflect invariant structures associated with categories but instead reflect people's dynamic ability to construct concepts. PMID- 2932521 TI - Discontinuity in cognitive skill. AB - Skill at reading geometrically transformed text improves as a function of practice across pages. A belief in continuity of learning must suppose a proportionate improvement in skill within pages. We tested for continuity of learning by comparing performance within pages with performance between pages, varying timing of text presentation and quantity of text presented for the purpose. Reanalysis of some published data and three new experiments indicated that skill is acquired continuously as a function of practice but is expressed discontinuously. We conjecture that the expression of skill requires perceptual segregation of tasks into task units to which skill is transferred, whereas acquisition of competence occurs as a strict function of practice. PMID- 2932522 TI - Grammatical priming of inflected nouns by the gender of possessive adjectives. AB - Two experiments examined the effect on lexical decision times for inflected Serbo Croatian nouns when the nouns were preceded by possessive adjectives (my, your, our). For any given pairing the possessive adjective and the noun agreed always in number (singular) and case (nominative) but only agreed half of the time in gender (masculine or feminine). Lexical decisions were faster when the noun targets were of the same gender as their primes. This gender congruency/incongruency effect was shown to hold whether the inflections of the adjective and noun were the same (as is the case for typical Serbo-Croatian nouns) or different (as is the case for atypical Serbo-Croatian nouns). The results are discussed in terms of a postlexical influence of grammatical processing on the recognition of individual words. PMID- 2932523 TI - The role of semantic information in episodic retrieval. AB - In two experiments, subjects studied lists of categorized words and then were tested for recognition of those words. Response time for a test word was speeded whenever the immediately preceding test word was from the same category. This was true even for test words (lures) from categories never studied. Thus it is argued that semantic information not present at the time of study affected retrieval. This finding is discussed with respect to the distinction between episodic and semantic memories. PMID- 2932524 TI - Hemisphere differences in the mood state-dependent effect for recognition of emotional faces. AB - Forty subjects viewed 10 pictures of facial expressions of emotion while they experienced a happy mood and 10 pictures while they experienced a sad mood. Later, while re-experiencing either a happy or sad mood, they were tested for recognition of these 20 target pictures intermixed with 20 distractors. Recognition of the 10 pictures seen earlier in a disparate mood was impaired significantly when they were presented at testing to the right hemisphere, but not when presented to the left. The right hemisphere appears to store the subject's mood as an integral part of a memory representation for an emotionally expressive face. When that face is presented at testing to the right hemisphere, recognition depends on whether the subject's test mood matches the mood stored in the representation. In contrast, the left hemisphere appears to store the subject's mood separately from encoded visual information about a face, and so recognition of a face presented at testing to the left hemisphere is unaffected by changes in mood. PMID- 2932525 TI - Transformations of visual memory induced by implied motions of pattern elements. AB - Four experiments measured distortions in short-term visual memory induced by displays depicting independent translations of the elements of a pattern. In each experiment, observers saw a sequence of 4 dot patterns and were instructed to remember the third pattern and to compare it with the fourth. The first three patterns depicted translations of the dots in consistent, but separate directions. Error rates and reaction times for rejecting the fourth pattern as different from the third were substantially higher when the dots in that pattern were displaced slightly forward, in the same directions as the implied motions, compared with when the dots were displaced in the opposite, backward directions. These effects showed little variation across interstimulus intervals ranging from 250 to 2,000 ms, and did not depend on whether the displays gave rise to visual apparent motion. However, they were eliminated when the dots in the fourth pattern were displaced by larger amounts in each direction, corresponding to the dot positions in the next and previous patterns in the same inducing sequence. These findings extend our initial report of the phenomenon of "representational momentum" (Freyd & Finke, 1984a), and help to rule out alternatives to the proposal that visual memories tend to undergo, at least to some extent, the transformations implied by a prior sequence of observed events. PMID- 2932526 TI - Judgments of natural and anomalous trajectories in the presence and absence of motion. AB - Recent studies have shown that many people demonstrate erroneous beliefs about motion when asked to predict the trajectories of objects. The present experiments examine whether people can select as correct natural trajectories over anomalous ones when presented with the actual on-going event (motion condition) or static representations of the event (no-motion condition). McCloskey's curved tube problem was used as the event. Results indicate that adults benefit from the motion information in these stimuli, choosing the correct path more often in the motion condition. Men performed better than women in both conditions; this gender effect could not be attributed to formal instruction in physics. Only in the no motion condition did any men prefer a path which reflected an impetus model of motion. Some women chose a curvilinear path in the motion condition, and in the no-motion condition the curvilinear path was their most often selected alternative. Fifth-grade children demonstrated no effect for gender and their path preferences resembled those of adult males. Children's responses failed to demonstrate a preference for those curvilinear paths which reflect an impetus based approach to the problem. Adults' performance in the no-motion condition was not enhanced by instructions to employ mental imagery of the event. PMID- 2932527 TI - Strategies of picture rehearsal: a comment on Proctor's (1983) article. PMID- 2932528 TI - How flexible is picture rehearsal? Discussion of Watkins' comment. PMID- 2932529 TI - A psychophysiological investigation of the continuous flow model of human information processing. AB - Twelve subjects responded to target letters "H" or "S" by squeezing dynamometers with the left or right hand. Targets could be surrounded by compatible (e.g., HHHHH) or incompatible noise (SSHSS) letters. Measures of the P300 component of the event-related brain potential and of correct and incorrect electromyographic and squeeze activity were used to study stimulus evaluation and response-related processes. When incorrect squeeze activity was present, execution of the correct response was prolonged, indicating a process of response competition. This process occurred more often under incompatible noise conditions, which were also associated with a delayed P300. Thus, the noise/compatibility manipulation influenced both stimulus evaluation and response competition processes. In contrast, a warning tone that preceded array presentation on half the trials, increased response speed without influencing evaluation time. The data suggest that the latency and accuracy of overt behavioral responses are a function of (a) a response activation process controlled by an evaluation process that accumulates evidence gradually, (b) a response priming process that is independent of stimulus evaluation, and (c) a response competition process. PMID- 2932530 TI - Flow structure versus retinal location in the optical control of stance. AB - In four experiments I examined the importance of the retinal center and periphery in the pickup of optical information for controlling stance as a function of the dynamic geometrical structure of the optical flow. All experiments were performed in a moving room so that the magnitude of compensatory sway in response to room movements could be measured. In Experiments 1 and 2 I found stronger sway response to flow having a largely lamellar structure that was presented to the retinal periphery than to more radially structured flow in the center. In Experiment 3 observers turned their heads to face the right wall of the room, placing radial flow in the periphery and lamellar flow in the center of the visual field. Radial flow presented to the retinal periphery induced no compensatory sway. Lamellar flow in the center of the retina produced some sway. Flow structure apparently interacts with the exposed retinal area in controlling stance. PMID- 2932531 TI - Constructing mental representations of objects from successive views. AB - A three-dimensional analogue of Hochberg's (1968) aperture viewing paradigm, the orthogonal slices task, examined the effects of complexity on processing objects. Ten subjects constructed, transformed, and compared mental representations of Shepard-Metzler (1971) figures varying in the number of component parts; processing time increased with complexity. A second study showed no effects of complexity on processing time when subjects merely judged the equivalence of the patterns used in the first study presented in sequence. Rather, constructed mental representations appear to preserve some of the spatial character of the corresponding objects. This conclusion was strengthened by the results of recognition tasks which showed that discrimination of constructed objects from appropriate distractors is better after subjects do the first (orthogonal slices) task than after they do the second (sequence matching) task. PMID- 2932532 TI - Allocation of attention in the visual field. AB - This research investigated whether attentional resources can be simultaneously allocated to several locations in a visual display, whether the mode of processing (serial or parallel) can be switched within a trial, and the nature of the costs when attentional resources are concentrated on an invalid location. Subjects were required to determine which of two target letters was present in eight-letter circular displays. In precue conditions, a primary and a secondary target location were designated 150 ms before target onset by an indicator that varied in validity. In the control conditions no cue was provided. A second experiment verified several assumptions that had been made in interpreting the data of Experiment 1. Modifications in Jonides' (1983) two-process model were suggested in terms of a zoom lens model of attentional resources. Instead of two alternative processing modes, attentional resources are conceived as capable of distribution over the visual field, but with low resolving power, or as continuously constricting to small portions of the visual field with a concomitant increase in processing power. PMID- 2932533 TI - Cognitive spatial processing and the regulation of posture. AB - Subjects performed the Brooks (1967) spatial and nonspatial memory tasks either while sitting or while maintaining a difficult standing balance position. The balance task disrupted spatial but not nonspatial memory performance. Balance steadiness during spatial and nonspatial memory conditions did not differ. These results suggest that cognitive spatial processing may rely on neural mechanisms that are also required for the regulation of posture. PMID- 2932534 TI - Orienting attention within visual fields: how efficient is interhemispheric transfer? AB - Five experiments are reported examining the effect of attentional orienting on lexical decisions within visual half-fields. In Experiment 1, following baseline performance, subjects were instructed to improve performance to the right or left of the fixation point. In Experiment 2, trials were run in blocks with all items to one side of the fixation point. In Experiment 3, completely valid position indicators as to the location of the next item to be shown were presented prior to the stimulus item. In Experiment 4, to examine practice effects, no instructions or cuing were given to subjects. In Experiment 5, subjects were urged to improve performance, but with no instructions as to location. As a summary of our results, it can be stated that (a) consistent visual field differences in lexical decision performance are present, even when subjects were informed, prior to viewing, of the spatial location of the next stimulus item. (b) Lexical decision information initially input to one cerebral hemisphere is primarily processed in that hemisphere. Interhemispheric transfer of this type of language information seems to be done primarily as the end product of a cognitive process. PMID- 2932535 TI - Location of influenza virus M, NP and NS1 proteins in microinjected cells. AB - When microinjected as cloned DNA, the nucleoprotein (NP) of influenza virus A/NT/60/68 (H3N2) accumulated in the nuclei of Xenopus laevis oocytes, and cultured cells of rodent and primate origin. This accumulation appeared to be specific and a property of the NP itself (or conceivably NP in association with unknown cellular constituents) since no other influenza virus components were present in DNA-injected cells. In the oocyte nucleus, clonally derived NP achieved an eightfold concentration over that in the cytoplasm. Such NP was full length as judged by its mobility during PAGE and had the native conformation of H3N2 virus NP according to its reaction with a panel of monoclonal antibodies. NP appeared to be in the soluble fraction of the nucleus as it did not sediment under conditions which removed particulate matter from nuclear extracts. Microinjection of extracts of chick embryo fibroblast cells infected with A/FPV/Rostock/34 (H7N1) showed that exogenous NP had an affinity for the nucleus similar to that synthesized intracellularly from cloned NP DNA. This conclusion was supported by an experiment in which cloned NP from the oocyte nucleus re entered the nucleus after injection into the cytoplasm of fresh oocytes. Injection of mRNA, extracted from chick embryo fibroblast cells infected with A/FPV/Rostock/34, into oocytes directed the synthesis of the viral proteins M (Mr 28 000), and NS1 (Mr 27 000) as well as NP (Mr 56 000). While NP from this source concentrated in the nucleus as before, M merely associated with the nucleus without exceeding the cytoplasmic level. Even more remarkable was NS1; although in injected cells this protein is concentrated in nucleoli, in microinjected oocytes its nuclear concentration was threefold less than that in the cytoplasm, despite the very large number (greater than 1500) of nucleoli present in Xenopus oocytes. It seems likely that the karyophilic nature of M and NS1, unlike that of NP, is a property not of the proteins themselves, but of a complex which they form with some other product of the infected cell. These findings were repeated when extracts from infected chick embryo cells containing NP, M and NS1 proteins radiolabelled in vivo, were injected into the cytoplasm of oocytes. PMID- 2932536 TI - Regulation of anterior pituitary D2 dopamine receptors by magnesium and sodium ions. AB - At D2 3,4-dihydroxyphenylethylamine (dopamine) receptors in anterior pituitary tissue, magnesium ions shifted receptors to agonist high-affinity states, but decreased the affinity of the antagonist [3H]spiperone. Conversely, sodium ions shifted the receptors to agonist low-affinity states, but increased the affinity of [3H]spiperone. Magnesium is proposed to stabilize the hormone-receptor-guanine nucleotide regulatory protein complex, whereas sodium appears to destabilize this ternary complex. Thus, magnesium and sodium appear to mediate their regulatory effects via a common component at the D2 dopamine-receptor ternary complex. PMID- 2932537 TI - Plasma catecholamines in Down's syndrome, at rest and during sympathetic stimulation. AB - Five adult female patients with Down's syndrome were compared with five age matched controls in the standing and cold pressor tests. In both tests, there were no differences between the two groups in heart rate, systolic and diastolic blood pressure or plasma noradrenaline, adrenaline and dopamine concentrations. However, plasma adrenaline tended to be higher in the Down's group, both in the standing and the cold pressor tests. PMID- 2932538 TI - Suppressor T cell changes in active multiple sclerosis: analysis with three different monoclonal antibodies. AB - This study demonstrates a significant reduction in the number of both total T cells and suppressor T cells identified by monoclonal antibodies in multiple sclerosis patients in acute relapse but not in those in remission. The reduction in the number of suppressor T cells was shown by all three monoclonal antibodies used but was most clearly demonstrated using Leu 2a rather than either OKT 8 or OKT 5. These findings suggest that the choice of monoclonal antibody used in a study of suppressor T cell numbers will influence the results and may help explain the lack of agreement in previous studies. PMID- 2932539 TI - Neuropathological classification of Huntington's disease. AB - In postmortem brain specimens from 163 clinically diagnosed cases of Huntington's disease (HD) the striatum exhibited marked variation in the severity of neuropathological involvement. A system for grading this severity was established by macroscopic and microscopic criteria, resulting in five grades (0-4) designated in ascending order of severity. The grade correlates closely with the extent of clinical disability as assessed by a rating scale. In five cases of clinically diagnosed HD there were no discernible neuropathological abnormalities (grade 0), suggesting that the anatomical changes lag behind the development of clinical abnormalities. In eight cases, neuropathological changes could only be recognized microscopically (grade 1). The earliest changes were seen in the medial paraventricular portions of the caudate nucleus (CN), in the tail of the CN, and in the dorsal part of the putamen. Counts of neurons in the CN reveal that 50% are lost in grade 1 and that 95% are lost in grade 4; astrocytes are greatly increased in grades 2-4. These studies indicate that analyses of the CN in grade 4 would reflect mainly its astrocytic composition with a component of remote neurons projecting to the striatum. Because of the relative preservation of the lateral half of the head of the CN in grades 1-2, these regions would reflect early cellular and biochemical changes in HD. PMID- 2932540 TI - Phosphatase activities in human glioma cells as revealed by light and electron microscopy--a preliminary study. AB - Alkaline phosphatase (ALPase) and Mg2+-activated ATPase (Mg2+-ATPase) activities were demonstrated in human brain tumors by light and electron microscopy. Four cases of glioma, i.e., two cases of astrocytoma, grade II, and two cases of glioblastoma, were used as materials. At the light microscopic level, Mg2+-ATPase activity was observed in the capillary wall and glial cells of both astrocytoma and glioblastoma. ALPase activity was restricted to the capillary wall. Its activity was stronger in glioblastoma than in astrocytoma. By electron microscopy, in astrocytoma, reaction product representing Mg2+-ATPase activity was distributed in the plasma membranes of endothelial cells and pericytes. Activity was primarily localized at the abluminal surface of endothelial cells and the surface of pericytes facing endothelium. The plasma membrane of glial cells was also positive. ALPase activity revealed essentially the same distribution pattern in blood vessels as above. In glioblastoma, on the other hand, activities of both phosphatases were markedly positive on the luminal surface of the plasma membrane of endothelial cells. They were much stronger than those along the abluminal endothelial surface. Phosphatase activities in brain tumor appear to change in localization pattern in association with glioma malignancy. This might reflect a functional aspect of changes in blood-brain barrier in glioma. PMID- 2932541 TI - Intact arch spondylolisthesis. A review of 50 cases and description of surgical treatment. AB - Over the past 11 years, the authors have treated 50 cases of intact arch spondylolisthesis. There were 38 female and 12 male patients, and all but 11 were older than 60 years of age. Almost all had severe low-back pain made worse by standing or walking. Other common manifestations were unilateral leg pain, numbness or weakness of the leg, and evidence of mild cauda equina compression. Severe cauda equina compression was rare. Myelography invariably showed an extradural dorsal compression. A waist deformity was characteristic in many patients, but 12 had a complete block. In 15 patients (30%) the myelographic impression was that of a herniated intervertebral disc. Most subluxations were of L-4 on L-5. At operation, the facets were found to be thickened, distorted, and irregular. All patients were treated with a wide decompression and laminectomy, which included a medial facetectomy of the inferior and superior facets. An intervertebral disc was removed in 10 patients. Follow-up monitoring of 41 patients (for an average period of 36 months) showed that 26 (63%) were pain free, 11 had less pain, and four were unimproved. Five other patients with short follow-up periods (average 5 months) were all improved. PMID- 2932542 TI - Effect of hematoporphyrin derivative photoradiation therapy on survival in the rat 9L gliosarcoma brain-tumor model. AB - Intracerebral tumors were produced in 99 rats by stereotaxic implantation of 9L gliosarcoma brain-tumor cells. Hematoporphyrin derivative (HPD), 10 or 20 mg/kg, was administered as an intravenous bolus 24 or 48 hours before irradiation of the tumor region with light from an argon pumped-dye laser (632 nm). Laser light, at a dose of 30, 60, or 200 joules/sq cm, was delivered through a craniectomy 10 or 13 days after tumor implantation. Survival times were significantly prolonged in rats exposed to laser light at a dose of 200 joules/sq cm 24 hours after administration of HPD, 20 mg/kg. PMID- 2932543 TI - Indium-111 oxine platelet survival in dogs: effect of doxorubicin and Dacron grafts. AB - The cytotoxic chemotherapeutic agent doxorubicin was found to acutely decrease platelet survival times in beagle dogs as determined using platelets labeled with [111In]oxine. Recovery was rapid, with platelet survival times returning to normal within 3 wk of cessation of treatment. Doxorubicin (1.5 mg/kg i.v. every 3 wk for a total of four doses) also delayed the return of platelet survival times to normal when given to beagle dogs following placement of thoracoabdominal aortic Dacron grafts. It is not known whether or not this may have clinical significance. PMID- 2932544 TI - Magnesium deficiency in the rat increases tissue levels of docosahexaenoic acid. AB - The effects of magnesium deficiency on tissue levels of total lipids and fatty acids were evaluated. Sprague-Dawley rats were fed a magnesium-deficient diet for 14 wk with controls being pair-fed to the deficient rats. Compared to the controls, serum and 24-h urinary magnesium levels were markedly lower in the magnesium-deficient rats. Serum cholesterol and total phospholipids were significantly higher in the magnesium-deficient rats than in the controls. Edema and polycystic degeneration of the kidneys were present in the magnesium deficient rats. Kidney total phospholipids and triacylglycerols were significantly lower in the magnesium-deficient rats than in the controls. The main change in tissue fatty acid composition in magnesium deficiency was the higher docosahexaenoic acid (22:6n-3) in serum, liver and aorta than in controls. The possible relationship of these findings to human alcoholism is discussed. PMID- 2932545 TI - Diagnostic laparoscopy under local anesthesia for evaluation of infertility. AB - Diagnostic laparoscopy is routinely performed in outpatient departments. At Stanford University's Gyn/Ob Department Clinic, this procedure is performed with the client's active cooperation by using local anesthesia. In addition to the significant benefit of decreased risk of surgical anesthesia, outpatient surgery is more convenient and more economical for the client and the facility. The laparoscopic procedure is described in detail. The facilities, nursing responsibilities, surgeon's qualifications, and criteria for patient selection are included. PMID- 2932546 TI - Effects of serotonin receptor agonists and antagonists on schedule-controlled behavior of squirrel monkeys. AB - The behavioral effects of the serotonin (5-HT) precursor l-5-hydroxytryptophan (l 5-HTP) and the phenylpiperazine 5-HT agonists 6-chloro-2-(1-piperazinyl)pyrazine (MK-212), 1-(m-trifluromethylphenyl) piperazine (TFMPP), 1-(m chlorophenyl)piperazine (CPP) and 2-(1-piperazinyl)quinoline (quipazine) were compared with those of the putative 5-HT antagonists metergoline, methysergide, cyproheptadine, cinanserin and ketanserin under a multiple 5-min fixed-interval schedule of food or electric shock presentation in squirrel monkeys. Intramuscular administration of l-5-HTP (0.3-17 mg/kg), MK-212 (0.01-1.0 mg/kg), TFMPP and CPP (0.03-10 mg/kg) produced dose-related decreases in responding under both the food- and shock-presentation schedules. Quipazine differed from the other 5-HT agonists in that it increased shock-maintained behavior at doses (0.1 1.0 mg/kg) that decreased responding maintained by food. The 5-HT antagonists produced mixed behavioral effects. Metergoline (0.03-1.0 mg/kg), cyproheptadine (0.1-1.0 mg/kg) and cinanserin (1.0-10 mg/kg) produced dose-related increases in responding maintained by food, whereas only metergoline and methysergide increased behavior maintained by shock presentation. The prototype 5-HT2-receptor ligand ketanserin (0.3-10 mg/kg) differed from the other 5-HT antagonists in that it decreased behavior maintained by either event. Thus, performances maintained by food or shock presentation reveal both qualitative and quantitative differences in the behavioral effects of 5-HT receptor agonists and antagonists. PMID- 2932547 TI - Discriminative-stimulus effects of midazolam in squirrel monkeys: comparison with other drugs and antagonism by Ro 15-1788. AB - Squirrel monkeys were trained to respond on one of two levers depending on whether midazolam (0.3 mg/kg) or saline had been injected. After i.v. injections of midazolam 10 consecutive responses on one lever either produced food or terminated a stimulus associated with electric shock, whereas after i.v. injections of saline 10 consecutive responses on the other lever either produced food or terminated the stimulus. The discriminative-stimulus effects of drugs were determined by administering cumulative doses i.v. during timeout periods that preceded sequential components of the experimental session. The benzodiazepines midazolam, chlordiazepoxide, diazepam and N-desmethyldiazepam, the cyclopyrrolone zopiclone and the triazolopyridazine CL 218,872 had qualitatively similar stimulus effects regardless of the type of consequence (food presentation or stimulus-shock termination) that maintained responding. Administration of each of these drugs resulted in greater than 90% of responses on the midazolam-associated lever at cumulative doses that did not severely suppress the overall rate of responding. The order of potency was: midazolam = diazepam greater than or equal to N-desmethyldiazepam greater than or equal to zopiclone greater than CL 218,872 greater than or equal to chlordiazepoxide. Administration of the 5-hydroxytryptamine antagonists cyproheptadine and cinanserin also resulted in greater than 90% of responses on the midazolam associated lever in about half the subjects, although these effects were observed only with cumulative doses that markedly reduced the overall rate of responding. Administration of pentobarbital, barbital, clozapine, muscimol, buspirone, diphenhydramine, tripelennamine, caffeine and Ro 15-1788 did not result in substantial responding on the midazolam-associated lever at doses up to those that reduced or eliminated responding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2932548 TI - Responses of muscle receptors in the kitten. AB - Responses have been recorded in single functional afferents supplying muscle receptors of the soleus muscle in kittens aged between 1 and 23 days. Recordings of nerve volleys in whole dorsal or ventral roots in response to muscle nerve stimulation showed that conduction velocity for afferent and motor fibres was similar and increased from 9 m s-1 in a 2-day-old animal to 33 m s-1 in a 23-day old animal. Of a total of 215 single functional axons isolated from 28 animals, 82 showed responses typical of tendon organs and 103 resembled muscle spindles, leaving 30 unidentified units. Both muscle spindles and tendon organs were characterized by having an over-all low firing rate compared with responses of adult receptors. The most immature receptors also lacked a maintained response to the hold phase of a ramp-and-hold stretch. Spindles in animals over the whole range of ages, including the youngest animals could be shown to be supplied with a fusimotor innervation. On a few occasions it was possible to isolate single fusimotor axons to a spindle; such axons were sometimes found to conduct impulses at a speed characteristic of non-myelinated fibres. Evidence was obtained for the existence of a beta-(skeletofusimotor) innervation of spindles. On four occasions it was possible to isolate single functional beta-axons in the ventral root. The incidence of beta-innervation appeared to be higher than in the adult. PMID- 2932549 TI - 1983 AAGL survey. Professional profile of the membership. AAGL Research and Survey Committee. AB - The average AAGL physician does general obstetrics and gynecology, with 135 deliveries, 41 hysterectomies and 38 IUD insertions a year in addition to about 50 laparoscopies for sterilization and 43 for diagnosis. About 1 in 10 will experience a major complication, and 1 in 25 will undergo medicolegal actions, although their complication rates as a group are no higher than those of the total membership. PMID- 2932550 TI - Prognostic value of subacute focal inflammation of the endometrium, with special reference to pelvic adhesions as observed on laparoscopic examination. An eight year review. AB - The significance of the endometrial lesion known as subacute focal inflammation (SFI) (or the more descriptive term lymphoid aggregates [LA]) as a factor in reproductive failure is controversial. We correlated the pelvic findings of 262 consecutive laparoscopic procedures performed for infertility with the histologic diagnosis from an endometrial biopsy that had been obtained previously as part of the infertility evaluations. Pelvic adhesions were observed in 87.3% of women in whom the diagnosis of SFI had been made. Pelvic adhesions were observed in only 10.9% of women whose biopsies did not contain SFI. Of women with SFI on biopsy but without pelvic adhesions, 70.6% demonstrated American Fertility Society stage I endometriosis at laparoscopy. These findings are statistically significant (P less than .0001). PMID- 2932551 TI - Uncommon indications for laparoscopy. AB - Laparoscopy was used as an ancillary method for infrequently occurring or unconventional indications in 140 patients. Diagnostic laparoscopy was done if other clinical, laboratory and biophysical methods were inconclusive or not conclusive in due time. Under some conditions operative laparoscopy or a combined vaginal and laparoscopic approach eliminated the need for laparotomy. No special equipment is required for such diagnostic and operative laparoscopy. PMID- 2932552 TI - How to prevent complications of open laparoscopy. AB - Infraumbilical minilaparotomy as a substitute for needle and trocar puncture continues to attract gynecologists for safety reasons. Although the open entry technique should eliminate aortic and iliac vessel injuries, other complications are occurring. In September 1984 a survey of 18 board-certified gynecologists who had performed a total of 10,840 open laparoscopies revealed 18 instances of wound infection and 6 cases of bowel laceration. Some features of surgical technique can minimize the risks of open laparoscopy. PMID- 2932553 TI - Persistent low back pain and leg length disparity. AB - Patients with low back pain who were found to have a leg length discrepancy were treated with a lift to the shoe on the short side. A small group of such patients with longstanding pain had major or total relief over a long period of followup. Clinical characteristics of the low back pain symptoms were distinctive. A useful method to establish leg length discrepancy clinically is described. PMID- 2932554 TI - The 'baby Brown' case and the Dr Arthur verdict. PMID- 2932555 TI - Localization of a base-paired interaction between small nuclear RNAs U4 and U6 in intact U4/U6 ribonucleoprotein particles by psoralen cross-linking. AB - The small nuclear RNAs U4 and U6 display extensive sequence complementarity and co-exist in a single ribonucleoprotein particle. We have investigated intermolecular base-pairing between both RNAs by psoralen cross-linking, with emphasis on the native U4/U6 ribonucleoprotein complex. A mixture of small nuclear ribonucleoproteins U1 to U6 from HeLa cells, purified under non denaturing conditions by immune affinity chromatography with antibodies specific for the trimethylguanosine cap of the small nuclear RNAs was treated with aminomethyltrioxsalen. A psoralen cross-linked U4/U6 RNA complex could be detected in denaturing polyacrylamide gels. Following digestion of the cross linked U4/U6 RNA complex with ribonuclease T1, two-dimensional diagonal electrophoresis in denaturing polyacrylamide gels was used to isolate cross linked fragments. These fragments were analysed by chemical sequencing methods and their positions identified within RNAs U4 and U6. Two overlapping fragments of U4 RNA, spanning positions 52 to 65, were cross-linked to one fragment of U6 RNA (positions 51 to 59). These fragments show complementarity over a contiguous stretch of eight nucleotides. From these results, we conclude that in the native U4/U6 ribonucleoprotein particle, both RNAs are base-paired via these complementary regions. The small nuclear RNAs U4 and U6 became cross-linked in the deproteinized U4/U6 RNA complex also, provided that small nuclear ribonucleoproteins were phenolized at 0 degree C. When the phenolization was performed at 65 degrees C, no cross-linking could be detected upon reincubation of the dissociated RNAs at lower temperature. These results indicate that proteins are not required to stabilize the mutual interactions between both RNAs, once they exist. They further suggest, however, that proteins may well be needed for exposing the complementary RNA regions for proper intermolecular base-pairing in the course of the assembly of the U4/U6 RNP complex from isolated RNAs. Our results are discussed also in terms of the different secondary structures that the small nuclear RNAs U4 and U6 may adopt in the U4/U6 ribonucleoprotein particle as opposed to the isolated RNAs. PMID- 2932556 TI - Copy number of the broad host-range plasmid R1162 is determined by the amounts of essential plasmid-encoded proteins. AB - DNA of the broad host-range plasmid R1162 contains a 1700 base-pair segment essential for plasmid maintenance. This region, RepI, consists of two cotranscribed genes encoding polypeptides with molecular weights of 29,000 and 31,000. Fusion of RepI to the strong tac promoter results in greatly increased amounts of at least one of these polypeptides. In trans, this construction has two other properties: it can raise the copy number of R1162, and it can protect this plasmid from loss due to incompatibility. Both effects require intact RepI genes. These properties of the RepI region, along with those of an origin-linked region described earlier, are discussed with respect to current models for control of plasmid copy number. PMID- 2932557 TI - Review of immunology for the periodontist. PMID- 2932558 TI - Elastic jump in male urethra during voiding: clinical observations in male subjects and experimental studies in dogs. AB - A physical phenomenon known as elastic jump occurs downstream of an elastic constriction applied to a collapsible tube. This flow anomaly is analogous to the hydraulic jump that occurs in surface flows. Some investigators have predicted that an elastic jump could occur in the male urethra (during voiding) in the cavernous segment between constrictions at the membranous and meatal regions. To identify and understand this flow anomaly, and to obtain clinical correlations in human male subjects we have attempted several radiological and urodynamic studies in normal and abnormal subjects. The studies were retrograde urethrography, voiding cystourethrography, static pressure recordings during voiding and uroflowmetry. Retrograde urethrography was believed to delineate accurately the anatomy of the bulbous urethra. Voiding cystourethrography showed the geometry of the functional bulb. Our observations in 43 male subjects suggest that the site and degree of elastic jump depend on the severity of bladder neck or prostatic obstruction, magnitude of detrusor pressure (energy) during voiding, degree of distal constriction and position in which the subject voids. The animal studies (23 dogs) confirmed our clinical urodynamic impression. PMID- 2932560 TI - Bilateral rectus femoris pedicle flaps for detrusor augmentation in the prune belly syndrome. AB - A 20-year-old patient with the prune belly syndrome presented with urinary retention and renal failure. In preparation for renal transplantation bladder rehabilitation, consisting of urethral dilation, reduction cystoplasty and detrusor augmentation with paired rectus femoris pedicle flaps, was undertaken. This procedure enabled the patient to empty the bladder totally by spontaneous voiding. Successful renal transplantation was performed subsequently and he has not required intermittent or continuous catheterization. The surgical approach and technique are described, and their application to other conditions of detrusor hypotonicity is discussed. PMID- 2932559 TI - Dichloromethylene-diphosphonate in patients with prostatic carcinoma metastatic to the skeleton. AB - A total of 17 patients with multiple osteoblastic bone metastases owing to prostatic carcinoma was treated with 2-dichloromethylene-diphosphonate, a powerful inhibitor of bone resorption. The drug was given intravenously (300 mg.) for 2 weeks and then orally (3,200 mg.) or intramuscularly (100 mg.) for 4 to 11 weeks. A definite improvement in pain, assessed by daily consumption of analgesic drugs and by an analogic scale, was observed within 10 days in 16 of the 17 patients. Four patients confined to bed rest for pain were able to walk after 2 weeks and reversal of paralysis also was noted in 1 patient. Transient changes in serum calcium (decreasing) and alkaline phosphatase (increasing) were observed in most patients. In the 3 patients in whom it was performed, repeated bone scanning showed a partial regression of pathological areas in 2 and the complete disappearance of most pathological areas in 1. Our results suggest that 2 dichloromethylene-diphosphonate may represent an important supportive treatment in patients with bone metastases owing to prostatic carcinoma, providing sustained relief of pain and regression of bone destruction without undesirable side effects. PMID- 2932561 TI - Long-term hemodynamic evaluation of lower extremity percutaneous transluminal angioplasty. AB - Percutaneous transluminal angioplasty (PTA) has provided an alternative method of treatment for occlusive disease of the lower extremities. However, the long-term durability of PTA compared with that of surgical reconstruction has not been adequately evaluated. This study was undertaken to assess the long-term hemodynamic results of PTA. Thirty-four dilatations performed on 28 patients over a 30-month period and followed for 1 to 53 months were reviewed. Twenty-two dilatations were done in the iliac arteries, seven in the superficial femoral, three in the popliteal, one in the peroneal artery, and one at a bypass graft anastomosis. All patients underwent noninvasive measurements of lower extremity segmental pressure prior to dilatation and at scheduled follow-up intervals. Success was defined as an increase in the Doppler-derived segmental lower extremity/brachial index of greater than or equal to 0.15 or normalization of the index (greater than or equal to 0.90), measured at the closest level distal to the site of dilatation. Sixteen of 22 iliac dilatations (72.7%) were initially successful. However, long-term success was maintained in only six (27.6%). Cumulative hemodynamic success for the initially successful iliac dilatations was 28% at 3 years. Seven of 11 (63.6%) dilatations performed on infrainguinal arteries were initially successful; however, only two (18.2%) experienced continued success. Cumulative hemodynamic success for the initially successful infrainguinal dilatations in this group was 35% at 3 years. Although immediate patency and improvement in hemodynamic parameters are similar to comparable surgical procedures, these results demonstrate that PTA is not as durable as conventional surgical procedures. PMID- 2932562 TI - Effects of antiplatelet agents in combination with endothelial cell seeding on small-diameter Dacron vascular graft performance in the canine carotid artery model. AB - The purpose of this study was to assess the success of endothelial cell-seeded and non-seeded small-diameter vascular grafts in dogs medicated with antiplatelet agents. Eighty dogs underwent bilateral carotid artery replacements with 6 cm lengths of 4 mm I.D. double-velour Dacron grafts. In each dog one graft was seeded with enzymatically derived autologous endothelial cells; the contralateral graft was nonseeded. The following anti-platelet medications were administered beginning 4 days preoperatively: aspirin (5 grains every day); dipyridamole (50 mg twice a day); aspirin plus dipyridamole (5 grains each day plus 50 mg twice a day); aspirin (1.25 grains every other day); ibuprofen (10 mg/kg/day); U-53,059, a cyclooxygenase inhibitor (3 mg/kg/day); and U-63557A, a thromboxane synthase inhibitor (10 mg/kg/day). Grafts were harvested 5 weeks postoperatively. Graft success was evaluated by patency, thrombus-free surface area, area endothelialized, and graft production of prostacyclin. None of the medications prevented neoendothelialization of seeded grafts. Mean patencies of endothelial cell-seeded grafts from medicated dogs were significantly greater than mean patencies of endothelial cell-seeded grafts from nonmedicated dogs. The cyclooxygenase inhibitors best maintained patency in nonseeded grafts. Thrombus free surface areas of endothelial cell-seeded grafts from medicated dogs were significantly greater than from nonseeded control grafts from the medicated dogs. All medications impaired prostacyclin synthesis. We conclude that the combination of endothelial cell seeding plus antiplatelet medication is most efficacious in small-vessel grafting success and that high levels of prostacyclin production by vascular grafts are not necessary to maintain patency in dogs medicated with antiplatelet agents. PMID- 2932563 TI - Minocycline-associated tooth discoloration in young adults. AB - After observing a patient with adult-onset tooth discoloration coincident with minocycline administration, we retrospectively surveyed a cohort of patients with severe cystic acne during therapeutic trials with isotretinoin. Four of 72 patients who had minocycline therapy during adolescence were found to have minocycline-associated tooth discoloration, which occurred in one case after only four weeks of treatment. Thus, minocycline must be considered as an uncommon cause of tooth staining in adults. PMID- 2932564 TI - Complication of a Hickman catheter. Cutaneous erosion of the Dacron cuff. PMID- 2932565 TI - [Influence of stellate ganglion block on the immune system]. PMID- 2932566 TI - Improvement of regional myocardial perfusion following percutaneous transluminal coronary angioplasty in patients with coronary artery disease. AB - The effect of percutaneous transluminal coronary angioplasty (PTCA) upon regional myocardial perfusion (RMP) was studied in 49 patients (Group I) using T1-201 myocardial scintigraphy (TMS) after exercise. Ten patients with unsuccessful PTCA (Group II) were tested for the reproducibility of measurements and for comparison. All patients had arteriographically documented coronary artery stenosis (greater than or equal to 70%) in at least one major coronary vessel. In group I, average coronary stenosis was 84.0 +/- 7.8% (mean +/- SD) before PTCA and 38.8 +/- 11.9% after PTCA (p less than 0.001). TMS was performed 3 days before and 4 days after PTCA using an arm-assisted step test. Myocardial perfusion images were obtained 5-10 min, 1 hour and 3-4 hours following the injection of T1-201 in anterior, LAO 45 degrees and LAO 80 degrees views. The T1 201 myocardial scintigram was interpreted by the authors. Each scintigram (anterior, LAO 45 degrees and LAO 80 degrees) was divided into 5 roughly equal segments. The perfusion of each segment was graded from 0 (no perfusion) to 3 (normal perfusion). Thus, for each patient a "total myocardial perfusion index (TMPI)" could be calculated, with a score of 45 indicating normal RMP. The total number of involved segments (TNIS) was also calculated as a sum of abnormally perfused segments. In group II, the reproducibility of both TMPI and TNIS was satisfactory (r = 0.97 and r = 0.93, each p less than 0.001). In group I, TMPI before PTCA was 37.8 +/- 4.8 at 5-10 min, 39.8 +/- 4.4 at 1 hr and 40.8 +/- 4.2 at 3-4 hrs. These values increased significantly after PTCA to 41.3 +/- 4.0, 41.9 +/- 4.1 and 42.0 +/- 4.0, respectively (each p less than 0.001). TNIS also decreased significantly following PTCA. Group I patients were further divided into 2 groups: patients with and without previous myocardial infarction. Although patients with previous myocardial infarction had significantly lower TMPI values and greater TNIS values than without previous myocardial infarction, these parameters improved significantly after PTCA. Therefore, we conclude that PTCA can improve exercise induced regional myocardial ischemia, if luminal diameter is dilated by more than 20%. Patients with previous myocardial infarction and persisting angina are also considered to be candidates for PTCA. PMID- 2932567 TI - [A case of cystadenocarcinoma developing from an ovary autografted to the abdominal wall]. AB - A 73-year-old woman developed an abdominal tumor. We performed tumor resection. The tumor, located between the fascia and peritoneum, was removed completely. The histological finding was cystadenocarcinoma. Thirty-eight years earlier she had undergone total hysterectomy and bilateral oophorectomy because of abnormal genital bleeding. At that time, her own ovary had been transplanted to the abdominal wall. We diagnosed this tumor as having developed from the autografted ovary. The complication of ovarian autografting is cystic degeneration. This complication is rare in Japan. Moreover, malignant change is extremely unusual in ovarian autografting. PMID- 2932568 TI - [Hormone therapy of breast cancer-its role in the treatment of breast cancer]. AB - Surgical hormone therapy and additive hormone therapy showed a response rate of about 30% for recurrent breast cancer, irrespective of kind of procedures or drugs. Additive hormone therapy had shorter duration of response than ablative surgery, but had still longer duration of response and less side effects than chemotherapy. Patients treated with tamoxifen alone as an initial therapy for their recurrent lesions had an over all survival time of 26 months in a median value, compared with 17 months for those treated with a combination chemotherapy. Initial treatment with tamoxifen alone eventually resulted in longer survival. To take maximum advantage of hormone therapy, it should be given in the early phase of recurrence, since ER status changes from positive to negative in the course of disease. PMID- 2932569 TI - [PET imaging of dementia]. PMID- 2932570 TI - [Subcortical dementia]. PMID- 2932571 TI - [Cardiovascular system transplantation. 7-2. Immunological effects of cyclosporine on canine ectopic heart transplantation]. PMID- 2932572 TI - [Cardiovascular system transplantation. 8. Effect of monoclonal anti-Ia antibody on graft survival in rat heart transplantation]. PMID- 2932573 TI - [Bilirubin conjugation disorder]. PMID- 2932574 TI - [Neonatal jaundice and enzyme induction therapy]. PMID- 2932575 TI - [67 cases of erythroderma]. PMID- 2932576 TI - [Epidermal Langerhans cells of experimentally induced acanthosis]. PMID- 2932577 TI - [Blood coagulation factor VIII complex in liver diseases]. PMID- 2932578 TI - [Measurement of canine pancreatic blood flow by Laser-Doppler flowmetry: blood flow response to gut hormones (VIP, PHI, GRP)]. PMID- 2932579 TI - [Cardiac morphology in left ventricular hypertrophy using thallium-201 myocardial scintigraphy]. PMID- 2932581 TI - [Care of children with severe mental and physical disabilities]. PMID- 2932582 TI - [Problems of handicapped children and administration policies]. PMID- 2932580 TI - [Patient education related to backache and knee pain given at an orthopedic service for outpatients]. PMID- 2932583 TI - [Interactions with handicapped children]. PMID- 2932584 TI - Wrapped-knitted Dacron and microporous EPTFE conduits for reconstruction of right ventricular outflow tract. AB - The use of the extracardiac conduit for the right ventricle to main pulmonary artery continuity facilitates repair of a wide variety of complex congenital cardiac malformations. Recently, concern has been directed to the appearance of proliferating and obstructive internal peels. In the present study on 18 mongrel dogs, wrapped-knitted Dacron, expanded polytetrafluoroethylene (EPTFE) and wrapped-knitted Dacron/EPTFE conduits were evaluated in the light of internal linings. Macroscopically, the wrapped-knitted Dacron conduits were covered with a thicker and poorly developed neointima, whereas, EPTFE conduits were internally covered with a thin neointima. Microscopically, the neointima on the former was not well healed, while that of the latter was well developed and anchored. Therefore, the EPTFE conduit seems to be superior to the wrapped-knitted Dacron conduit and EPTFE conduit can be used clinically. PMID- 2932585 TI - Effects of intraperitoneal administration of OK-432 for patients with advanced cancer. AB - The effects of intraperitoneal administration of OK-432 on tumor cells in ascites, in relation to the infiltration of effector cells and on the immune responses of the host, particularly, with regard to immune suppressive mechanisms, were investigated in 25 patients with cancerous ascites. The effects of OK-432 depended on frequency of the repeated and continuous administrations through a tube placed in the peritoneum during laparotomy. Infiltrations of neutrophils and lymphocytes were observed in the ascites within a short period after the administration and monocyte infiltration followed. Disappearance of tumor cells correlated well with the infiltration of these cells. No marked changes in the proliferative responses of peripheral blood lymphocytes were noted and decreases in serum inhibitory factor levels in sera were observed in patients given larger doses of OK-432. A marked reduction in Concanavalin-A-induced suppressor cell activities was observed after OK-432 administration. OK-432 administration probably leads to a disappearance of tumor cells by enhancing peritoneal effector cell activities and by inhibiting the induction of suppressor cell activities, in a dose dependent manner. PMID- 2932586 TI - [A case of respiratory muscle tic]. PMID- 2932587 TI - Effect of 4-hydroxyphenylretinamide and retinoic acid on proliferation and cell cycle of cultured human breast cancer cells. AB - The synthetic retinoid 4-hydroxyphenylretinamide (HPR) showed antiproliferative effect on cultured human breast cancer cells, which were sensitive to retinoic acid (RA) too. Investigation of the cell cycle by flow cytophotometry showed a significant increase of cells in the S-phase of the cell cycle after 24 hours of RA treatment, whereas HPR did not show this effect. After 4-7 days of retinoid treatment, the percentage of resting cells increased. The influence on the cell cycle and the antiproliferative effect were more pronounced for RA than for HPR treatment in both cell lines investigated (ZR-75.1 and 734 B). PMID- 2932588 TI - Effects of dichloromethylene diphosphonate on the osteolytic and osteoplastic effects of rat prostate adenocarcinoma cells. AB - A model system of prostate adenocarcinoma (PA) in Lobund-Wistar rats is described in which the transplanted tumor cells (PA-III) were inoculated sc over the calvaria. A local tumor developed that, when attached to the bone, caused erosion and fragmentation of the bone, with adjacent osteoplastic changes and metastases to the lungs. The attachment of the tumor to the bone was enhanced if the periosteum was scratched during the inoculation of tumor cells. The destructive effect on bone structure was also induced by in vivo transplanted PA-I and PA-IV cells, but not by PA-II cells. In rats that were pretreated with dichloromethylene diphosphonate, the local PA-III tumors developed with metastases to the lungs, but the calvariae were intact. PMID- 2932589 TI - Percutaneous transluminal coronary angioplasty. PMID- 2932591 TI - [Roentgen endovascular and endocardial surgery--a new trend in cardioangiology]. PMID- 2932590 TI - [Prevention of disorders in the contractile function of non-ischemic sections of the heart during experimental infarction using beta-endorphin]. AB - The effect of pretreatment with beta-endorphin on disorders of right-atrial myocardial distensibility and contractility in left-ventricular infarction (by Selye) was examined in Wistar rats. This peptide, administered intravenously (50 micrograms/kg) immediately before the simulation of infarction, was shown to reduce considerably infarction-induced impairment of distensibility and contractility of an isolated right atrium and of its resistance to hypoxia and excessive calcium, and also to increase the survival rate. The results of the study suggest that the protective effect of beta-endorphin is chiefly due to its central action. PMID- 2932592 TI - [Characteristics of the surgical procedure in acute cholecystitis in middle-aged and elderly patients]. PMID- 2932594 TI - [Curative decompression of the gallbladder in acute cholecystitis]. PMID- 2932593 TI - [Therapeutic and diagnostic endoscopy in obstructive jaundice of benign etiology]. PMID- 2932596 TI - [Advisability of using muscles in hernioplasty]. PMID- 2932595 TI - [Diagnosis and treatment of mechanical jaundice]. PMID- 2932597 TI - [Removable continuous layered suture of the abdominal wall]. PMID- 2932598 TI - Prevalence of sleep apnea in healthy industrial workers. AB - The present study reports on polysomnographic findings of sleep apnea syndrome in a representative sample of otherwise healthy middle-aged blue collar workers (age 45.7 +/- 8.5) with normal to borderline blood pressure (systolic 135.5 +/- 16.1; diastolic: 88.3 +/- 10.2), mild overweight (Broca 114.9 +/- 14.7) and with reported nocturnal sleep disturbances. The prevalence of sleep apnea in this sample (N = 20 out of a total of 78 workers with reported sleep disturbances) is 40%. Mean frequency of apnoeic episodes during night was 97.6 +/- 42.7 in the apnea-positive group as compared to 27.1 +/- 19.9 in the apnea-negative group (T = 5.0; p less than 0.0001), with an apnea index of 13.3 +/- 6.2 as compared to 3.5 +/- 2.3 (T = 7.2, p less than 0.0001). Left ventricular hypertrophy (mean diameter of end diastolic left ventricle: 64.0 +/- 9.5 mm) was found in individuals with apnea although manifest hypertension was absent in most individuals. PMID- 2932600 TI - Atrial natriuretic factor--a new hormone affecting kidney function. AB - A family of biologically active peptides (atrial natriuretic factor - ANF) has recently been identified in mammalian heart atria. The peptides derive from a common 152 amino acid precursor and at least 1% of total messenger RNA activity is specific for the factor. When injected intravenously ANF is hypotensive and natriuretic. Data indicate that atrial natriuretic factor represents a newly discovered hormone involved in the regulation of blood pressure and volume. Cellular release of ANF does not require the activation of the adenylate cyclase system, but is associated with receptor-mediated activation of the cellular polyphosphoinositide mechanism. The natriuretic effect includes increased glomerular filtration rate and specific inhibition of normal sodium reabsorption from the medullary collecting duct. The mechanism of this transport inhibition is not yet known. PMID- 2932599 TI - Antibody-induced glomerular injury. PMID- 2932602 TI - [Renal handling of alcohol and its tubular effects]. AB - The renal handling of ethanol comprises glomerular filtration and tubular reabsorption. Due to its high permeability alcohol concentration in the tubular fluid approaches that of peritubular fluid and under steady state conditions alcohol concentration in the final urine is almost the same as in serum water. Even in high concentrations alcohol does not significantly interfere with kidney cell function. This seems to be due to the fact that renal tissue is almost free from alcohol dehydrogenase. Thus, acetaldehyde, the cytotoxic intermediate of alcohol metabolism, is not accumulated in effective doses. If applied directly in micropuncture experiments alcohol is without distinct effects while acetaldehyde inhibits the main parameters of cellular vitality as measured by electrical membrane potentials and intracellular ion activities. PMID- 2932603 TI - The school nurse's role in assisting children with disabling conditions. PMID- 2932601 TI - [Mechanisms of postobstructive polyuria]. AB - Postobstructive diuresis occurs after relief of bilateral ureteral obstruction despite the persistent decrease in renal cortical perfusion and glomerular filtration rate (GFR). After an initial transient rise in renal blood flow (RBF) during acute ureteral obstruction, tubular damage and progressive vasoconstriction with decreased RBF, especially of medullary perfusion, are observed with chronic obstruction. These are associated with an activation of the renin-angiotensin system and of renal prostaglandin (PG) synthesis with enhanced production of the vasoconstrictor thromboxane A2. Azotemia and extracellular fluid volume (ECFV) expansion result from impaired renal function. Mechanisms of polyuria following relief from bilateral chronic obstruction include enhanced PGE mediated medullary blood flow, structural and functional tubular damage with decreased sodium reabsorption and (vasopressin-resistant) impaired renal concentrating ability, osmotic diuresis, activation of natriuretic factors following ECFV-expansion, and sometimes iatrogenic excessive fluid replacement. The resulting loss of fluid and electrolytes represents a major hazard in patients after surgical correction of congenital or acquired urinary tract obstruction. PMID- 2932604 TI - Haemodynamics of coronary artery-saphenous vein bypass. AB - The velocity distribution of a suspension of red blood cell ghosts in an idealized model of the coronary artery-saphenous vein bypass has been investigated with the aid of laser Doppler anemometry. Pulsatile flow simulated pressure variations in the ascending aorta and ghost cell velocities were determined by the Doppler shift of scattered laser light. Using four different model bypasses it was demonstrated that turbulent flow at the graft-coronary intersection can be delayed by decreasing the discontinuity in diameter between the bypass vein and coronary artery, and also by reducing the bypass vein and host coronary artery intersection angle. PMID- 2932605 TI - [Absence of the antihypertensive effect of chronic treatment with prazosin in the spontaneously hypertensive rat (SHR) and their offspring]. AB - Seven consanguine monogamous SHR couples (G 1) were treated from their 5th to their 39th week of age with prazosin, 100 micrograms/kg/day i.p. Male rats were treated without interruption. Treatment was withheld in female rats from delivery to weaning. They were compared to seven similar SHR couples who were only daily i.p. injected with the same volume of solvent. Second (G 2) generation rats (untreated were studied. In G 1 female rats only, prazosin induced a transient decrease in systolic blood pressure (SBP), 6 hours after the injection, at 25 weeks of age. SBP, heart weight/body weight ratio and plasma renin activity remained unchanged at 39 weeks of age. Gestational parameters were not changed by the treatment, and no parameter was changed in G 2 rats. A previous study in the same conditions with another alpha 1-adrenoreceptor blocking agent, nicergoline, showed an inhibition of hypertension development in G 1 rats together with a preventive effect on untreated G 2 SHR (Moore et al., 1983). Thus prazosin failed to produce similar antihypertensive effects both in the treated rats and in their offspring and one can therefore conclude that nicergoline's effects were not only due to alpha 1-adrenoceptor blockade. PMID- 2932606 TI - 50 cases of acne treated by puncturing acupoint dazhui in combination with cupping. PMID- 2932607 TI - Use of parental advisors in the development of a parental coping scale. PMID- 2932608 TI - Proliferative and cytotoxic immune functions in aging mice. III. Exogenous interleukin-2 rich supernatant only partially restores alloreactivity in vitro. AB - The ability of exogenous interleukin-2 (IL-2) rich supernatant to restore the defective T cell mediated immune functions of spleen cells from aged C57BL/6 mice was analyzed. Addition of IL-2 rich supernatant to allogeneic mixed lymphocyte cultures (MLC) resulted in an increase in the proliferative response of spleen cells from both young and old mice. The MLC response of cells from old mice was, however, not restored to the level of proliferation seen with splenocytes from young animals. In studying the generation of specific T cell suppressor function, it was found that IL-2 rich supernatant enhanced this function only for spleen cells from those aged animals which demonstrated a defective response in its absence. The response of these mice was thereby restored to the normal level. The response of cells from young control animals and aged mice with normal suppressor activity was not affected by the addition of IL-2 rich supernatant. We conclude that decreased IL-2 production constitutes a functionally important aspect, but is by no means the only defect in the immune response of aged mice. The results also suggest that responsiveness to IL-2 is less affected by age than lymphokine production. PMID- 2932609 TI - Suppression of murine natural killer cell activity by adherent cells from aging mice. AB - Natural killer (NK) cell activity declines with age in mice. The purpose of this study was to investigate the effect of peritoneal and splenic adherent cells from young and old mice on NK activity to determine whether adherent cell suppressor function might contribute to this decline. Peritoneal adherent cells from old mice suppressed NK activity of young splenic non-adherent indicator cells more than peritoneal cells from young mice. Splenic adherent cells from old but not from young mice also suppressed this activity. That (1) the suppressive activity of the adherent cell populations was not affected by treatment with anti-Thy-1 plus complement, and that (2) the adherent cell population contained 77-92% cells positive for alpha-naphthyl acetate esterase activity, suggests that the active adherent suppressor cell may be a macrophage. Therefore, the age-related decline in NK activity in mice can be explained, in part, by an increase in adherent cell suppressor function. PMID- 2932610 TI - Age-related change in activation by Tris (hydroxymethyl) aminomethane on myosin ATPase activity of human minor pectoral muscles. AB - Age related change of the human minor pectoral muscles was biochemically demonstrated. Myosin-ATPase activity was significantly decreased with age, and was activated with Tris. The degree of the activation by Tris was observed to be lower in old aged patients than in the young. Furthermore, at low concentration of CaCl2 (less than 100 microM), myosin-ATPase activity was higher in the young age than in the old, while at high concentration of CaCl2 (more than 1 mM) no significant difference was observed between young and old age. Decrease with age in activation by primary amine such as Tris would play an important role in the muscle working capacity in old age. PMID- 2932611 TI - The influence of health on school outcomes. A multivariate approach. AB - This study investigates the relationship between chronic poor health and school outcomes among children. A simultaneous three-stage least squares model is estimated in which achievement and attendance are endogenous variables. The hypothesis that particular health characteristics are associated with differences in individual school outcomes is confirmed. For example, attendance is affected most by illnesses likely to interfere with school or peer interactions or difficulty doing only strenuous activity. Achievement is lowered by moderate to severe psychologic problems. Including attendance as an endogenous variable increases its significance. Other socioeconomic and school variables, such as mother working, marital status and special schooling, are included in the model. Policy implications are suggested. PMID- 2932613 TI - [Complications in connection with percutaneous transluminal angioplasty]. PMID- 2932612 TI - Immunologic effects of nonsteroidal anti-inflammatory agents. AB - The author discusses the evidence that PGE is an immunomodulator and addresses the thesis that nonsteroidal anti-inflammatory agents, by blocking endogenous PGE production, act to partially correct the immunologic aberrations involved in the pathogenesis of rheumatoid arthritis. PMID- 2932614 TI - [Severe ischemic vascular disease of the legs. PTA as an acceptable complement to vascular surgery]. PMID- 2932615 TI - [Clinical relevance of beta-hexosaminidase activity in the urine]. PMID- 2932616 TI - [Topical treatment of acne vulgaris with clindamycin]. PMID- 2932617 TI - Behavioral effects and benzodiazepine antagonist activity of Ro 15-1788 (flumazepil) in pigeons. AB - The selective benzodiazepine receptor antagonist, Ro 15-1788, produced behavioral effects in pigeons at doses at least 100 times lower than those previously reported to possess intrinsic pharmacological activity in mammals. In contrast to its effects in mammalian species, in pigeons, Ro 15-1788 does not exhibit partial agonist activity. Key-peck responses of pigeons were studied under a multiple fixed-interval 3-min, fixed-interval 3-min schedule in which the first response after 3-min produced food in the presence of red or white keylights. In addition, every 30th response during the red keylight produced a brief electric shock (punishment). Under control conditions, punished responding was suppressed to 30% of unpunished response levels. Ro 15-1788 (0.01 mg/kg, i.m.) increased unpunished response rates by 33% without affecting rates of punished responding. Doses of 0.1 to 1.0 mg/kg Ro 15-1788 produced dose-related decreases in both punished and unpunished responding. As is characteristic of other benzodiazepines, midazolam (0.1 and 0.3 mg/kg, i.m.) markedly increased punished responding but had little effect on rates of unpunished responding. Ro 15-1788 antagonized the increases in punished responding and also reversed the rate-decreasing effects of higher doses of midazolam. However, the effectiveness of Ro 15-1788 as a benzodiazepine antagonist was limited by its intrinsic activity: rate-decreasing doses of Ro 15 1788 were unable to completely reverse behavioral effects of midazolam. Midazolam was an effective antagonist of the behavioral effects of Ro 15-1788 (up to 0.1 mg/kg) but midazolam did not influence the rate-decreasing effects of 1.0 mg/kg Ro 15-1788 across a 100-fold dose range. In the pigeon, the behavioral effects of relatively low doses of Ro 15-1788 (0.01-0.1 mg/kg) appear to be related to benzodiazepine receptor mechanisms, whereas other systems appear to be involved in the effects of higher doses. PMID- 2932619 TI - Percutaneous measurement of portal blood flow in the piglet by continuous thermodilution. AB - The continuous thermodilution method was applied to the percutaneous measurement of portal blood flow in the piglet by inserting a thermodilution probe into the portal vein via the transhepatic transvenous route. The method was compared to electromagnetic flowmetry in three piglets; the two methods yielded statistically identical results. The coefficient of variation of the continuous thermodilution measurements was 4%. The method allows portal blood flow measurements that are instantaneous, reliable, reproducible, and repetitive. It was applied to a study of rapid flow variations in piglets receiving an infusion of posterior pituitary extract. PMID- 2932620 TI - Osteoarthritis XI: Lumbar spondylosis. PMID- 2932621 TI - [Organization of visiting lecture series for the advanced qualification of the head nurses of treatment and prevention institutions]. PMID- 2932618 TI - Normal excretion of quinolinic acid in Huntington's disease. AB - We measured the excretion of the endogenous neurotoxin quinolinic acid in 14 patients with Huntington's disease and in 11 age matched control subjects. Huntingtonian patients excreted less quinolinic acid, than controls. When normalised to urea or creatinine output quinolinic acid excretion was normal. We conclude that Huntington's disease is not associated with a generalised disturbance of quinolinic acid metabolism, however, a local hyperproduction of quinolinic acid cannot be excluded from our results. PMID- 2932622 TI - [Work of a nurses' council]. PMID- 2932623 TI - [Control of smoking among medical school students]. PMID- 2932624 TI - [Role of yeasts of the genus Candida in the transformation of the hydrocarbon energy in oil-contaminated gray-brown soil]. AB - Energy transformation was studied in the processes of hydrocarbon metabolism by microorganisms in oil-contaminated grey-brown soil. For such microbial populations as Candida species which use hydrocarbon substrates only as an energy source but not for growth, the criteria of biomass or incidence are presumed to have a relative significance for revealing the comparative functional role of these populations in the self-purification of oil-contaminated soils. Therefore, it is necessary to simultaneously assay both the incidence and the functional activity of microorganisms expressed in terms of respiration intensity. A diagram is proposed which shows the role of Candida yeasts in transforming the energy of aromatic and paraffin hydrocarbons in oil-contaminated soils. PMID- 2932625 TI - Two-component laser Doppler anemometer for measurement of velocity and turbulent shear stress near prosthetic heart valves. AB - The velocity and turbulent shear stress measured in the immediate vicinity of prosthetic heart valves play a vital role in the design and evaluation of these devices. In the past hot wire/film and one-component laser Doppler anemometer (LDA) systems were used extensively to obtain these measurements. Hot wire/film anemometers, however, have some serious disadvantages, including the inability to measure the direction of the flow, the disturbance of the flow field caused by the probe, and the need for frequent calibration. One-component LDA systems do not have these problems, but they cannot measure turbulent shear stresses directly. Since these measurements are essential and are not available in the open literature, a two-component LDA system for measuring velocity and turbulent shear stress fields under pulsatile flow conditions was assembled under an FDA contract. The experimental methods used to create an in vitro data base of velocity and turbulent shear stress fields in the immediate vicinity of prosthetic heart valves of various designs in current clinical use are also discussed. PMID- 2932626 TI - Treatment of Paget's disease of bone. PMID- 2932627 TI - [Economic significance of zoonotic cutaneous leishmaniasis in the Uzbek S.S.R]. PMID- 2932628 TI - [Effect of malathion on mosquitoes]. PMID- 2932629 TI - [Isolation of Tahyna virus from mosquitoes collected in Dushanbe]. PMID- 2932630 TI - [Congenital cardiac abnormalities and trisomy 21. Frequency, type of association and hemodynamic aspects]. PMID- 2932631 TI - Dopamine D2 receptor binding sites for agonists. A tetrahedral model. AB - In order to develop a model for the putative binding sites between the D2 dopamine receptor and many of its agonists, we obtained the dissociation constants of many dopaminergic agonists at the high affinity state, D2high, as well as at the low affinity state, D2low, of the receptor. [3H]Spiperone was used to label the D2 dopamine receptors in porcine anterior pituitary tissue. Agonists without any hydroxyl groups, such as 2-aminotetralin, effectively inhibited the binding of [3H]spiperone; the addition of a hydroxyl group corresponding to the "meta" position in dopamine, however, enhanced the potency (in four series of agonists) by an order of magnitude. The R-(-)-enantiomers of the aporphines and 5,6,-dihydroxy-2-dipropylaminotetralin were more potent than the S-(+) enantiomers. Although the 4-methoxy-2-dipropylaminoindans were potent, the R-(-) 11-methoxyaporphines were not. A tetrahedral model is proposed; this has two sites for agonist attachment, the extremities of the sites being separated by 8 A, and their functional groups directed between 15 degrees and 30 degrees off the orthogonal from the receptor surface. Several steric obstacles are required to account for the inactivity of several congeners. PMID- 2932632 TI - Thymidylate synthase overproduction and gene amplification in fluorodeoxyuridine resistant human cells. AB - Cytotoxicity to 5-fluoro-2'-deoxyuridine (FdUrd) derives from its conversion to 5 fluorodeoxyuridine-5'-monophosphate, which binds to and inhibits thymidylate synthase (TS) in the presence of the cofactor, 5,10-methylenetetrahydrofolate. We have selected FdUrd-resistant variants of the human cell line HEp-2 following adaptation to stepwise increases in drug concentration. In the initial selection, maximal drug resistance was associated with a 26-fold increase in the cellular level of TS. Greater TS overproduction (80-fold) was obtained by selection for FdUrd resistance in the presence of 10 microM folinic acid and 100 microM deoxyinosine. The latter agents were included to expand the folate pool to ensure adequate levels of cofactor during the selection process. Using cDNA plasmid pMTS 4, which is complementary to mouse TS mRNA, we show that TS overproduction in the HEp-2 variants is accompanied by a 100-fold increase in TS mRNA and a 100-fold amplification of the TS structural gene. Thus, TS overproduction and gene amplification is a mechanism of resistance to FdUrd in human cells. PMID- 2932633 TI - [Parental guilt experience in diseases of their children]. AB - Parents of sick or handicapped children often exhibit strong guilt feelings. These can be justified but equally can be irrational, based on magic, prescientific thinking. However, quite often they have an emotionally stabilising function for the parents. Using clinical examples possible reasons for, and the importance of these parental guilt feelings in coping with the disease are analysed. Suggestions for dealing with these guilt feelings in a differentiated manner are formulated. PMID- 2932634 TI - Asbestos-associated disease: can the issues be resolved in the courtroom? PMID- 2932635 TI - Frameshift mutagenesis in the repressor gene of bacteriophage lambda: influence of a C/G----T/A transition upon the mutability by 9-aminoacridine of an adjacent run of 4 G/C base pairs. PMID- 2932636 TI - The development of central cores in both fiber types in tenotomized muscle. AB - Using the histochemical reaction for myosin adenosine triphosphatase (ATPase), a study of the rat soleus muscle following tenotomy was undertaken. It was demonstrated that both type 2A and 2C fibers undergo degenerative changes following tenotomy. All previous studies have stated that only type 1 fibers were affected and developed central core lesions and that type 2 fibers were somehow protected from the degenerative process. The results of this experiment illustrate that central core lesions will develop in all three fiber types (types 1, 2A, and 2C) of the soleus following tenotomy. PMID- 2932637 TI - Parvalbumin in cross-reinnervated and denervated muscles. AB - The extensor digitorum longus (EDL) muscle was cross-reinnervated by the soleus (SOL) nerve, leading to the well-known transformation toward a slow muscle. Nine weeks after the operation, the quantitative analysis of the Ca2+-binding protein, parvalbumin (PV), using high-performance liquid chromatography, showed a threefold reduction of PV in the cross-reinnervated EDL muscle. Denervation of the EDL muscle, which leads to an increase of the half-relaxation time, resulted in a 20% decrease of the PV concentration within 4 days. This significant lower PV level was detectable prior to any change of the myofibrillar adenosine triphosphatase (ATPase). Normal PV concentrations were reached after 9 weeks following self-reinnervation of the EDL muscle. The experiments support the view that PV is involved in the relaxation of rat fast skeletal muscles and that its expression is dependent on nerve-muscle interaction. Since PV changes preceded histochemical changes after denervation, this protein may be a sensitive marker for early stages of neuromuscular disturbances. PMID- 2932638 TI - Control of myofibrillar ATPase activity and force in myodystrophic muscle. AB - Myofibrillar ATPase activity was measured as a function of the free calcium concentration in skeletal muscles of control and myodystrophic mice. In addition, the force developed in skinned extensor digitorum longus (EDL) fibers of control and myodystrophic mice was measured as a function of the free calcium concentration, and a histomorphometric study was performed on soleus and EDL muscles of control and myodystrophic mice. The results showed that the myofibrillar ATPase activity and the force-generating mechanisms of control and myodystrophic muscles were controlled to the same relative degree by equivalent concentrations of calcium ions. Upon maximal activation of the ATPase activities, we measured 18% less activity in myodystrophic muscles than in control muscles. Maximal activation of the force-generating capacity in skinned fibers showed there was no significant difference in force produced in the control compared to myodystrophic fibers. The histomorphometric study revealed no alteration in the relative distribution of different fiber types in myodystrophic compared to control muscles. However, the histomorphometry did reveal a larger slow (type 1) relative cellular area compared to total cross-sectional area in myodystrophic muscle than in controls. We propose that the lower ATPase activity but equal force-generating capacity of myodystrophic muscles compared to control muscles is due to myodystrophic muscles being composed of a greater fraction of myofibrils from slow (type 1) fibers than control muscles. PMID- 2932639 TI - Rat diaphragm: changes in muscle fiber type frequency with age. AB - This study demonstrates age-related changes in fiber type, distribution, and diameter that suggest that the diaphragm does not attain a static pattern of fiber type in adults. Furthermore, the progressive increase in the FG fiber diameters may be of importance in the interpretation of physiologic and biochemical parameters measured in the diaphragm muscle of animals of different age groups. PMID- 2932640 TI - Beta-oxidation enzymes in normal human muscle and in muscle from a patient with an unusual form of myopathic carnitine deficiency. AB - In a reported patient with myopathic carnitine deficiency, addition of exogenous carnitine to muscle homogenates failed to correct palmitate oxidation, and oral carnitine was of no clinical benefit. In a muscle biopsy from this patient, we found that, in contrast to the marked deficiency of free carnitine (3% of normal) short- and medium-chain acylcarnitines were in the normal range and long-chain acylcarnitine was increased almost four times. As this result confirmed the hypothesis of a muscle defect of mitochondrial oxidation of palmitate, all eight enzymes of beta-oxidation were measured spectrophotometrically in the muscle extract. None of them was found to be defective. These data suggest that the underlying biochemical abnormality in this patient may be a deficiency of the carnitine-acylcarnitine translocase system or a defective interaction between acyl-CoA dehydrogenase and its flavoprotein coenzyme. PMID- 2932641 TI - Effects of long-term physical training and detraining on enzyme histochemical and functional skeletal muscle characteristic in man. AB - The adaptability of human skeletal muscle to increased (training) and decreased (detraining) usage was studied in 11 athletes over a 42-month-long observation period. Biopsies were taken from the deltoid and the quadriceps muscle, together with measurements of maximum torque output during voluntary knee extensions at high relative to slow speeds of movement. A 16% and 14% decrease in the proportion of type I fibers was seen in the proximal arm and leg muscles, respectively, in the detraining subjects. This conformed with the changes in muscle function. On the other hand, in the training subjects, who increased their activity level through systematic daily physical training over an almost 4-year long period, there were no significant changes seen in fiber type proportions of either arm or leg muscles. This was presumably due to the smaller net change in physical activity level caused by training as compared to detraining in the subjects of this study. Thus, the results show that fiber type proportions in intact human skeletal muscle are not exclusively determined by heredity, but may also be influenced by environmental factors, such as physical activity level. PMID- 2932642 TI - Aldosterone-receptor deficiency in pseudohypoaldosteronism. AB - Pseudohypoaldosteronism, a syndrome characterized by salt wasting and failure to thrive, usually presents in infancy as high urinary levels of sodium despite hyponatremia, hyperkalemia, hyperreninemia, and elevated aldosterone levels. We have investigated this syndrome for the possibility of abnormal Type I or "mineralocorticoid-like" receptors, which have intrinsic steroid specificity indistinguishable from that of renal mineralocorticoid receptors and are found in many tissues and cells, including mononuclear leukocytes. We have studied three patients with pseudohypoaldosteronism: the 28-year-old index case in Melbourne (Patient 1) and two siblings in Munich, eight and two years of age (Patients 2 and 3); clinically, Patient 3 had a less severe case than his sister. Percoll separated control monocytes bound [3H]aldosterone with high affinity (Kd approximately 3 nM) and limited capacity (150 to 600 sites per cell). On repeated examination, no [3H]aldosterone binding was found in monocytes from Patients 1 and 2; in Patient 3, the levels were 62 sites per cell, more than 2 S.D. below those of the control. Levels in the parents of the Munich patients (first cousins) were normal. It appears that pseudohypoaldosteronism is caused by a Type I receptor defect, that the defect may be complete or partial, that transmission may be autosomal recessive, and that the study of patients with pseudohypoaldosteronism may indicate physiologic roles for Type I receptors in nonepithelial tissues. PMID- 2932644 TI - Transfusion-induced immunologic abnormalities not related to AIDS virus. PMID- 2932643 TI - Male pseudohermaphroditism due to multiple defects in steroid-biosynthetic microsomal mixed-function oxidases. A new variant of congenital adrenal hyperplasia. AB - A six-month-old 46,XY infant with a female phenotype and ambiguous genitalia was evaluated for male pseudohermaphroditism. The principal findings were (1) low basal plasma levels of all measured C19 steroids and their sulfates, which were unchanged or only minimally increased after stimulation with human chorionic gonadotropin or ACTH, (2) no urinary metabolites of C19 11-deoxy steroids, and decreased amounts of C19 11-oxosteroids, (3) normal basal plasma cortisol levels and normal urinary excretion of cortisol metabolites, (4) high plasma corticosterone and deoxycorticosterone levels and elevated urinary excretion of their metabolites, (5) high plasma progesterone and pregnenolone levels and increased urinary excretion of pregnanediol and pregnenediol, (6) high plasma 17 alpha-hydroxyprogesterone and 21-deoxycortisol levels and increased urinary excretion of pregnanetriol, 17 alpha-hydroxypregnanolone, and pregnenetriolone, (7) high plasma and urinary levels of 5-pregnene-3 beta,20 alpha-diol sulfate, (8) low plasma levels of 21-hydroxy-pregnenolone and 5-pregnene-3 beta,17 alpha, 20 alpha-triol sulfate, (9) high plasma ACTH levels, and (10) suppression of the high plasma steroid levels by dexamethasone. The unusual pattern of plasma and urinary steroids indicated that this child had multiple abnormalities of steroid biosynthetic microsomal mixed-function oxidases--21-hydroxylase, 17 alpha hydroxylase, and 17,20 desmolase. The deficit in the activities of the first two enzymes resulted in decreased cortisol synthesis with subsequent increased ACTH secretion and adrenocortical hyperplasia. The male pseudohermaphroditism resulted from deficient testosterone synthesis due to deficiency of 17 alpha-hydroxylase and 17,20 desmolase. The mother and two sisters of the affected child had evidence of mild 17 alpha-hydroxylase deficiency. PMID- 2932645 TI - Plasma concentration of atrial natriuretic factor in normal pregnancy. PMID- 2932647 TI - Snack-induced release of atrial natriuretic factor. PMID- 2932646 TI - Atrial natriuretic hormone, the renin-aldosterone axis, and blood pressure electrolyte homeostasis. AB - The renin-angiotensin-aldosterone axis exerts major control over sodium and potassium balance and arterial blood pressure. These three functions are continuously regulated by changes in angiotensin II and aldosterone levels in response to wide variations in dietary intake of sodium and potassium. In addition, changes in intrarenal physical factors cause changes in the supply of distal tubular sodium that, in turn, work to determine sodium and potassium excretion and to modulate the release of renal renin. However, certain aspects of sodium homeostasis cannot be fully explained either by the activity of the renin system or by intrarenal physical factors, and this has led investigators to search for other natriuretic hormonal mechanisms. Recently, it has become clear that atrial tissue contains a group of peptides, at least one of which is probably secreted as a regulatory hormone. In animals, these atrial peptides produce immediate, marked natriuresis associated with a rise in glomerular filtration rate (but no alteration of total renal flow) and a simultaneous decrease in arterial blood pressure. Atrial peptides also inhibit renal renin secretion and adrenal cortical secretion of aldosterone, and they oppose the vasoconstrictive action of angiotensin II. One of these atrial peptides may therefore be the long-sought natriuretic hormone, though in a different form and shape than was envisioned. The fact that atrial peptide works to oppose the renin system at four points suggests that this new hormone could have a major complementary role in long-term regulation of blood pressure and electrolyte homeostasis. In this construction the renin system primarily defends sodium balance and blood pressure, with the atrial hormone having an increasing counter influence in situations involving high blood pressure or sodium surfeit. We can soon expect to learn more about this atrial hormone, including which peptide is the active circulating hormone, what induces or inhibits its release, and what part it plays in cardiovascular diseases. PMID- 2932648 TI - Establishment of idiotypic helper T-cell repertoires early in life. AB - Immunoglobulin variable-region (V) genes, it is now recognized, do not encode specific receptors for T lymphocytes. Classical observations on T-cell expression of immunoglobulin idiotypes had remained unexplained until recent experiments showed that immunoglobulin idiotypes expressed by T lymphocytes in normal mice are absent in cells of the same specificity isolated from donors whose B-cell system has been suppressed by administration of anti-mu antibodies from birth. This observation provided evidence for the 'learning' of T-cell idiotypes from the B-cell/antibody system and, therefore, for the importance of idiotypic network interactions in the selection of available lymphocyte repertoires before antigenic challenge. Previously described influences of B cells and/or antibodies on the T-helper (Th) cell compartment would appear to operate at the level of clonal repertoires by complementarities with defined immunoglobulin idiotypes. Other authors, however, had previously shown the striking stability of T-cell idiotype expression in chimaeric animals reconstituted with T and B cells originating from donors showing differential idiotype expression. We have now investigated this apparent discrepancy and present here results demonstrating that immunoglobulin-dependent selection of T-cell (idiotypic) repertoires only operates for the first 3 weeks of life. PMID- 2932649 TI - Abolition of specific immune response defect by immunization with dendritic cells. AB - Murine cytotoxic T (Tc)-cell responses to various antigens are controlled by immune response (Ir) genes mapping in the major histocompatibility complex (H-2). The genes responsible are those encoding the class I and class II H-2 antigens. The H-2 I-Ab mutant mouse strain bm12 differs from its strain of origin, C57BL/6 (H-2b), only in three amino acids in the I-A beta bm12 class II H-2 molecule. As a consequence, female bm12 mice are Tc-cell nonresponders to the male antigen H-Y and do not reject H-Y disparate skin grafts. We now report that bm12 mice generate strong H-Y-specific Tc cells following priming in vivo and restimulation in vitro with male bm12 dendritic cells (DC). Female bm12 mice primed with male DC also reject male skin grafts. Furthermore, we demonstrate that only responder cell populations containing a mixture of L3T4+ (T-helper (Th) phenotype) and Lyt 2+ (Tc phenotype) T lymphocytes generate H-Y-specific Tc cells. These data imply an essential role for Th cells, activated by DC as antigen-presenting cells (APC), in changing H-Y-nonresponder bm12 mice into H-Y responders. Priming and restimulation with DC allows the triggering of a T-cell repertoire not demonstrable by the usual modes of immunization. This principle might be used to overcome other specific immune response defects. PMID- 2932651 TI - [Transcranial sonographic monitoring of the blood flow of the middle cerebral artery in recanalizing operations of the extracranial internal carotid artery]. AB - During endarterectomy of the internal carotid artery (ICA) blood flow velocity of the ipsilateral medial cerebral artery (MCA) was continuously monitored in twelve patients with the help of a new transcranial pulsed Doppler system. Additionally, the basal cerebral arteries where examined pre- und postoperatively in order to evaluate criteria for selective intraoperative shunting and to document flow improvement following ICA reconstruction. All patients had symptoms, either of TIA or of minor stroke. Five of them had in addition a contralateral ICA occlusion. During intraoperative carotid cross-clamping on the patients with unilateral ICA lesions, MCA blood flow dropped to zero in only one of them. In the other cases, a 20 to 60% flow reduction occurred indicating cross-filling or/and collateral blood supply via the posterior circulation. More severe MCA flow reductions were found in patients with contralateral ICA occlusion, with the occurrence of a no-flow state in two of them. All patients were operated on with an indwelling shunt. Its effect on MCA blood flow varied considerably. Apparently, the shunt was necessary in some patients but was superfluous in the majority of them. Transcranial Doppler meets the basic criteria of an examination technique to be recommended for monitoring. The method is noninvasive. The parameter, i.e. MCA flow velocity, can be evaluated on-line. It is representative and highly sensitive for cerebral circulatory disturbances and impending ischemia in the carotid territory. Transcranial MCA flow monitoring does not affect the course of the operation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2932650 TI - Phencyclidine increases the affinity of dihydropyridine calcium channel antagonist binding in rat brain. AB - Phencyclidine (PCP) significantly reduces the apparent dissociation constant (KD) of the dihydropyridine (DHP) calcium channel antagonist, [3H]nitrendipine, in synaptosomal membranes of rat and mouse brain without significantly effecting the maximum binding capacity (Bmax). At an optimum concentration of PCP (10 microM) the apparent KD of [3H]nitrendipine was reduced from 178 +/- 9 pM to 112 +/- 9 pM in rat forebrain, a 58% increase in affinity. The structural derivatives of PCP, P-Br-PCP [1-[1-(4-bromo-phenyl-cyclohexyl)piperidine]], m-NH2-PCP [1-[1-(3-anilo) cyclohexyl]piperidine], (+/-)-PCMP [1-(1-phenyl)-cyclo-hexyl-3-methylpiperidine] also increased the apparent affinity of [3H]nitrendipine in the following order, p-Br-PCP much greater than PCMP greater than PCP greater than m-NH2-PCP. Local anesthetics either reduced the apparent affinity of [3H]nitrendipine or had no effect. Kinetic analysis revealed that PCP both increased the microassociation rate constant and decreased the microdissociation rate constant of [3H]nitrendipine. The magnitude of this enhanced binding varied with the brain region studied; the greatest increase in apparent affinity of [3H]nitrendipine was observed in striatum, while no significant increase in affinity was observed in brainstem. In some brain areas, PCP was more effective in reducing the KD in crude homogenates than in washed tissue. PCP (10 microM) did not alter the KD of [3H]nitrendipine to rat cardiac tissue. Both Ca2+ and Mg2+ inhibited the effect of PCP, while monovalent ions were ineffective in this regard.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2932652 TI - Power spectral analysis and cortical coupling of EEG for young and old normal adults. AB - Power spectral analysis and cortical coupling were computed on eyes closed EEG recorded from 80 normal volunteers: 20 females and 20 males aged 25-35 years and 20 females and 20 males aged 55-70 years. Recordings were from Fz, Cz, C3, Pz and Oz areas. The results indicate that with increased age there was a greater uniformity of EEG activity across the brain. Magnitude of EEG power was significantly less variable across recording sites for the old than for the young. In addition, cortical coupling values were reliably higher for the older subjects indicating a greater congruity among EEG patterns. The EEG power and cortical coupling measures were significantly correlated and thus may indicate an underlying mechanism common to both. The results support a theory of decreased central inhibitory function in old age and may reflect an age-related breakdown of functional autonomy of cortical areas. Gender had no significant effect on either EEG power or cortical coupling. PMID- 2932653 TI - Effect of ethanol on adenosine triphosphatase and enolase activities in rat brain and in cultured nerve cells. AB - The effect of alcohol on enzymes involved in energy metabolism of nervous tissue were analyzed, in vivo after acute and chronic ethanol administration to rats and in vitro by addition of 50 mM and 100 mM ethanol to the medium of cultured nerve cells: chick neurons, chick glial cells, a neuronal cell line (MT17) and a glial tumoral cell line (C6). The parameters we measured were (Na+, K+), Mg2+ and ecto Ca2+, Mg2+ ATPase activities involved in transport phenomena and enolase activities (non neuronal NNE and neuron specific enolase NSE) as markers of nerve cell maturation. In vivo, after chronic ethanol administration (Na+, K+) ATPase activity was increased while Mg2+ dependent activity was not affected. Enolase activity was decreased. Acute ethanol administration decreased (Na+, K+) ATPase activity, while Mg2+ dependent activity was not affected. In cultured nerve cells ethanol effect was dose, time and cell type dependent; alterations of the cell membrane by trypsinization of the tissue before seeding modifies the effect of ethanol on the enzymes we analyzed. Our results suggest that alcohol effect on nerve cells depends mainly on the lipoprotein structure of the cell membranes which may have different properties from one cell type to another. PMID- 2932654 TI - Dopaminergic modulation of the diethylstilbestrol-induced proliferation of the anterior pituitary gland of the Fisher 344 rat. AB - Bromocriptine (CB 154), a potent agonist upon the D-2 receptor, blocks the proliferation of the mammotrophs and the elevation of serum prolactin concentration induced by chronic exposure of male Fisher 344 rats to diethylstilbestrol (DES). Fluphenazine, a dopamine receptor antagonist, blocks these effects of CB 154. We conclude that a D-2 receptor occurs on the proliferating mammotroph of the male Fisher 344 rat and that stimulation of this receptor inhibits prolactin release and stops the DES-induced proliferation of these cells. PMID- 2932655 TI - Lipid storage myopathy in Kearns-Sayre syndrome. AB - A 7-year-old girl had external ophthalmoplegia, limb weakness, short stature, hearing loss, pigmentary degeneration of the retina, and increased CSF protein content. Muscle biopsy revealed vacuolar myopathy with accumulation of lipids. Electronmicroscopy showed abnormalities of shape, size, and internal structure of muscle mitochondria. Muscle activity of palmitoyl-CoA synthetase was decreased, and the content of lipids was increased. Serum and muscle carnitine levels were normal, as were muscle carnitine palmitoyltransferase and carnitine acetyltransferase. PMID- 2932656 TI - Senile dementia of Alzheimer's type (SDAT): reduced T8+-cell-mediated suppressor activity. AB - We compared patients with senile dementia of the Alzheimer's type (SDAT) and age matched controls with respect to T8+-cell-mediated suppressor function using a pokeweed mitogen (pwm)-induced IgG secretion assay. The responding B cells were allogeneic to the T-regulator cells. T8+-cell-mediated suppression was lower in SDAT patients than the controls when we used either 2 X 10(4) or 5 X 10(4) T8+ cells. Suppressor function was lower in both SDAT and elderly controls than in young adults. SDAT patients and controls did not differ with regard to T4+-cell mediated helper activity. In SDAT patients, there seems to be an exaggeration of the age-related decline in suppressor-cell function. Whether such changes reflect accelerated changes of intrinsic lymphocyte properties or aberrant neural influences on lymphocytes remains to be resolved. PMID- 2932657 TI - Sleep disturbances and severity of Huntington's disease. AB - We studied sleep functions in two patients with mild and five with moderately severe Huntington's disease. In mild disease there was chorea, but intelligence, mental function, and sleep were all normal. In moderately severe disease, intelligence and mental function were also affected, and there was a sleep disturbance characterized by prolonged sleep-onset latency, increased interspersed wakefulness, and reduced sleep efficiency. PMID- 2932658 TI - Hemodynamic evaluation of transluminal iliac artery balloon dilatation. AB - In order to document the hemodynamic results of transluminal iliac artery balloon dilatation, 23 aortoiliac segments were evaluated before and after treatment. Hemodynamic parameters were: intra-arterial common femoral pressure measurements, indirect ankle pressure measurements and femoral velocity waveform analysis. The segments were divided into group (a) aortoiliac segments with an open superficial femoral artery (n = 8), and group (b) aortoiliac segments with an occluded superficial femoral artery (n = 15). In group (a) all patients were free of symptoms and ankle pressure improved significantly six months after dilatation. Velocity waveform analysis of the common femoral artery did not correlate with this improvement. In group (b) intra-arterial pressure measurements showed improvement in 60% (9/15) after six months. Ankle pressure measurements and velocity waveform analysis did not correlate with the intra-arterial pressure changes. Transluminal iliac artery balloon dilatation of iliac stenosis in patients with an open superficial femoral artery can be evaluated by indirect ankle pressure measurements. In patients with iliac stenosis in combination with occluded superficial femoral arteries intra-arterial pressure measurements are needed to demonstrate hemodynamic improvement. PMID- 2932660 TI - Rat muscle spindles deficient in elements of the static system. AB - Motor nerve supplies to 15 poles of rat lumbrical spindle were reconstructed from serial, 1-micron transverse sections of muscle embedded in resin. Neural and muscular elements associated with the modulation of static sensitivity of afferents were deficient in these spindles relative to cat tenuissimus and rat soleus spindles. Rat lumbrical spindles contained fewer static fusimotor axons, fewer static chain intrafusal fibers, fewer motor-innervated static bag2 and chain fibers and fewer secondary afferents. The sparsity of static elements in spindles of the rat lumbrical muscle may correlate with the distal location or with the delicate motor tasks performed by the muscle. PMID- 2932659 TI - D2 dopamine receptor-mediated inhibition of forskolin-stimulated adenylate cyclase activity in rat striatum. AB - Forskolin markedly stimulates striatal adenylate cyclase activity in a concentration-dependent manner, and at 10(-4) M produces an approximate 40-fold increase in enzyme activity above basal levels. Dopamine (in the presence of 100 nM SCH 23390), bromocryptine and quinpirole (LY 171555) significantly inhibit both basal and forskolin-stimulated adenylate cyclase activity. There is a significant increase in the absolute but not in the percent inhibition of enzyme activity by dopaminergic agonists as a function of forskolin concentration. This inhibition is agonist-concentration dependent and antagonized by the D2 antagonist, spiperone. These results suggest that forskolin may be used as a tool for amplifying the abolute D2-receptor-mediated inhibition of adenylate cyclase in rat striatal homogenates. PMID- 2932661 TI - Evaluation of the 5-hydroxytryptamine receptor agonist 8-hydroxy-2-(di-n propylamino)tetralin in different rodent models of epilepsy. AB - The effects of the serotonin (i.e. 5-hydroxytryptamine; 5-HT) S1 receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), and the 5-HT precursor L-5-hydroxytryptophan (5-HTP) were compared in different models of epilepsy. 5-HTP significantly increased the threshold for electroconvulsions and pentylenetetrazol-induced seizures in mice and rats but exerted no anticonvulsant effects in epileptic gerbils and amygdaloid-kindled rats. The anticonvulsant effect of 5-HTP against electroconvulsions in rats could be attenuated by the S2 receptor antagonist, ketanserin. 8-OH-DPAT displayed no anticonvulsant effects in the seizure models examined but gave rise to proconvulsant effects in mice. Differences between 5-HTP and 8-OH-DPAT were also observed in terms of behavioural changes in response to both drugs. The data indicate that S2 receptors may be involved in the anticonvulsant effect of 5-HTP. PMID- 2932662 TI - Adrenal function in acute severe asthma. AB - Adrenocortical function was assessed by the intravenous short synacthen test in 22 control subjects and 68 patients admitted to hospital with acute severe asthma. The cortisol increment was subnormal in 19 of the 68 asthmatics. This included 11 of the 14 patients on continuous oral steroids, seven of the 29 patients who had had occasional courses of oral steroids, one of the seven on inhaled steroids only, and none of the 18 who had had no steroids. Adrenal suppression was greatest in those patients taking oral steroids in divided daily doses. Nineteen of 43 patients were on or had taken oral steroids in this fashion. Of those 19 patients with low cortisol increments only one half had received supplementary steroids in the 24 hours preceding admission. Based on the synacthen test, serum DHEA-SO4 values were not a good discriminant of adrenocortical function. Adrenal insufficiency may be an important cause of death in acute severe asthma in New Zealand. PMID- 2932663 TI - Low dose hepatitis B vaccination of hospital staff. PMID- 2932664 TI - Soft tissue injuries and physiotherapy. PMID- 2932665 TI - Management of low back pain. PMID- 2932666 TI - Group B streptococcal necrotizing fasciitis arising from an episiotomy. AB - A case of extensive necrotizing fasciitis arising from an episiotomy is presented. Group B beta-hemolytic streptococcus and Staphylococcus aureus were isolated. Prompt recognition and aggressive therapy resulted in a favorable outcome despite significant morbidity. Salient clinical features of this rare postpartum complication are discussed and previous cases are reviewed. In addition to wide surgical resection, therapy included aggressive volume resuscitation with Swan-Ganz catheter monitoring, the use of military antishock trousers (MAST suit) to control diffuse hemorrhage, and temporary application of porcine xenografts. PMID- 2932667 TI - The dental management of the drug-dependent patient. PMID- 2932668 TI - Committee on Hearing and Equilibrium guidelines for reporting treatment results in Meniere's disease. PMID- 2932670 TI - Effects of radiation therapy on T-lymphocyte subpopulations in patients with head and neck cancer. AB - Cellular immunity was assessed in 85 patients with head and neck cancer with monoclonal antibodies to lymphocyte surface antigens that identify total T cells, helper cells, and suppressor cells. The control group consisted of 22 healthy volunteers. Nine patients who had surgical procedures for benign diseases were also studied. Compared with the controls, the patients with cancer who received radiation therapy had a significant decrease in total lymphocytes, T cells, helper cells, suppressor cells, and decreased helper/suppressor cell ratio. Significant decreases in lymphocyte subpopulations were not detected in patients tested before treatment or in patients treated with surgery alone. The immune deficits observed were prolonged in duration, with some present in the patients studied up to 11 years after radiation therapy. This long-lasting immune depression may have relevance to tumor recurrences and second primaries in patients with head and neck cancer treated by radiation therapy and to attempts at increasing cure rates with adjuvant agents that improve immune reactivity. PMID- 2932669 TI - Components of the alternative pathway of complement in otitis media with effusion. AB - An evaluation of the alternative pathway of complement was undertaken in patients with otitis media with effusion (OME). Middle ear fluid (MEF) and serum specimens were obtained from 34 patients at the time of elective myringotomy for OME. Bacterial, viral, and mycoplasma cultures were made for all specimens of the fluids. Immunochemical determinations by radial immunodiffusion were performed for C3, C5, factor B, properdin, factor H, factor I, and albumin. Each patient's recent clinical course and past history were reviewed. The results of all viral and mycoplasma cultures were negative. Three of 55 bacterial cultures were positive for type B Haemophilus influenzae. All components of the alternative pathway measured were found to be present in varying amounts in MEF. When the levels of the complement components were compared to the clinical factors studied, there were no observable differences. These data suggest that components of the alternative pathway of complement are present in OME and are not useful in predicting the clinical course or outcome of this disorder. PMID- 2932671 TI - Unraveling the effects of compensation, litigation, and employment on treatment response in chronic pain. AB - Although it has often been suggested that chronic pain patients who are receiving workmen's compensation or who have litigation pending are less likely to benefit from treatment, the results of outcome studies of this question conducted by various pain clinics have been inconsistent. We hypothesized that poorer outcome in such patients may be related to the fact that they are less likely to be working and that the inconsistent results in the literature may therefore be explained by variability among studies in the percentages of patients who are receiving compensation (or who have litigation pending) who are also working. We examined the relationships among compensation, litigation, employment, and short- and long-term treatment response in a series of 454 chronic pain patients. Compensation benefits and employment status both predicted poorer short-term outcome in univariate analyses; however, when employment and compensation were jointly used to predict outcome in multiple regression analyses, only employment was significant. In additional analyses, only employment significantly predicted long-term outcome, whereas compensation and litigation did not. Our results suggest that it would be valuable to redirect attention away from the deleterious effects of the 'compensation neurosis' and toward the roles of activity and employment in the treatment and rehabilitation of chronic pain patients. PMID- 2932672 TI - CT of complicated inflammatory bowel disease in children. AB - Most children with inflammatory bowel disease do not need a CT scan. However, when the course becomes complicated it often is necessary to evaluate what is happening outside the bowel lumen. CT is the examination of choice for that evaluation. With CT, the presence and extent of an abscess can be diagnosed and followed; fistulae can be detected; bowel wall and mesenteric thickening can generally be differentiated from an abscess. PMID- 2932673 TI - Gruntzig angioplasty dilatation of an esophageal stricture in an infant. PMID- 2932675 TI - Pulsed Doppler determinations of cardiac output in neonates: normal standards for clinical use. AB - Noninvasive monitoring of cardiac output can greatly facilitate the clinical assessment and management of neonates with cardiovascular compromise. To assess normal values of cardiac output in neonates, mean blood flow velocity was measured in the ascending aorta from a suprasternal approach using a range-gated, pulsed Doppler velocity meter, and aortic root diameter was determined from an M mode echocardiogram. These techniques were combined, and cardiac output was evaluated in 59 healthy premature and 62 term newborn infants during the first week of life. Birth weights ranged from 780 g to 4,740 g and gestational age from 27 to 42 weeks. Cardiac output values increased linearly with advancing birth weight (r = +.94, P less than 0.001) and gestational age (r = +.95, P less than .001). Mean cardiac output values (+/- SD) per kilogram of body weight were 249 +/- 34 mL/min/kg and decreased with advancing birth weight: less than 1,500 g = 265 +/- 32 mL/min/kg; 1,500 to 2,500 g = 253 +/- 34 mL/min/kg; and greater than 2,500 g = 241 +/- 33 mL/min/kg. For clinical use, 325 mL/min/kg and 200 mL/min/kg can be used as upper and lower limits of normal, respectively. Doppler cardiac output estimates compared favorably with studies using invasive techniques. PMID- 2932674 TI - Hyperoxia-induced pulmonary vascular and lung abnormalities in young rats and potential for recovery. AB - We carried out morphometric studies to assess the effects of increasing durations of hyperoxic exposure on the developing rat lung and to evaluate the potential for new growth and for regression of structural abnormalities on return to room air. From day 10 of life Sprague-Dawley rats were either exposed to hyperoxia (0.8FIO2) for 2-8 wk or were removed after 2 wk and allowed to "recover" in room air for 2-6 wk. Litter mates maintained in room air served as age matched controls. Every 2 wk experimental and control rats from each group were weighed and killed. The heart and lungs were removed, the pulmonary artery was injected with barium-gelatin, and the lung was fixed in formalin in the inflated state. Morphometric assessments were made of right and left ventricular weights, lung volume, axial artery lumen diameter, alveolar number and concentration, and arterial number, concentration and muscularity. Rats continuously exposed to hyperoxia and rats exposed for only 2 wk showed the same degree of impaired parenchymal lung growth, as judged by a decrease in the concentration and number of alveoli. A significant decrease in arterial concentration, increase in muscularization of peripheral arteries, and medial hypertrophy of muscular arteries occurred after 2 wk of hyperoxia. Despite an initial trend toward regression, these features became progressively severe with continued hyperoxic exposure and by 8 wk were associated with a decreased arterial lumen diameter, with right ventricular hypertrophy and with failure to thrive.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2932676 TI - Partial reconstruction of the platelet membrane-cytoskeleton complex. AB - The order of attachment of the purified platelet cytoskeletal proteins to the isolated platelet membrane has recently been determined and it has been shown that only F-actin would interact directly with the membrane. Subsequently alpha actinin and only then, ABP, would attach in that sequence. More recently the role of the platelet membrane glycoproteins Ib, IIb and IIIa in the binding of the cytoskeleton to the membrane has been investigated. The evidence suggests that F actin attaches to the membrane via IIb and IIIa and the association of ABP with the cytoskeleton appears to be related to both its ability to interact with the F actin-alpha-actinin complex as well as the glycoprotein Ib. PMID- 2932677 TI - Mechanism of regulation of calcium concentration by platelet membranes. AB - Calcium is recognised as an important messenger in the platelet activation. Both the external and internal membranes are considered to play an important role in the Ca2+ homeostasis of the cell. The aim of this review is to try to understand the mechanisms of regulation of the cytoplasmic free Ca2+ concentration by both kinds of membranes and mainly by internal membranes. PMID- 2932678 TI - Preliminary functional characterization of a 24,000 dalton platelet surface protein involved in platelet activation. AB - We have recently investigated three monoclonal antibodies, FMC 8, FMC 48 and FMC 56, directed against a 24,000 dalton (24K) cell surface protein on human platelets and pre-B progenitor cells. These monoclonal antibodies (at 0.1-10 micrograms/ml) were found to be potent inducers of platelet aggregation with normal and with aspirin-treated platelets. FMC 8 Fab' and FMC 56 (Fab')2 fragments blocked aggregation induced by intact antibody. The Fab' and (Fab')2 fragments, however, were ineffective by themselves (at 100 micrograms/ml) as platelet agonists but augmented (at 10-25 micrograms/ml) the aggregation response of normal and aspirin-treated platelets to threshold concentrations of ADP. It has been suggested that the 24K cell surface protein may be identical to a 24K cAMP-dependent phosphoprotein involved in regulating transmembrane calcium flux. To examine this, 32P-phosphate-loaded platelets were treated with prostaglandin E1 to raise intracellular cAMP levels and then analysed on two-dimensional O'Farrell gels. No labelled phosphoprotein corresponded in mobility to the 24K cell surface protein. Further, FMC 56 failed to immunoprecipitate a 24K phosphoprotein. The combined results suggest that the three monoclonal antibodies activate platelets via a prostaglandin-independent and as yet undefined mechanism which requires the intact bivalent antibody for full platelet response. Fab' fragments (monovalent) and (Fab')2 fragments (altered Fab-Fab configuration) are ineffective as platelet agonists but can augment the response of other stimuli. Thus, further studies with this system should allow delineation of those intracellular events necessary for partial and full platelet responses. PMID- 2932679 TI - Sequence of the T4 recombination gene, uvsX, and its comparison with that of the recA gene of Escherichia coli. AB - We have determined the nucleotide sequence of the uvsX gene of bacteriophage T4 which is involved in DNA recombination and damage repair, and whose product catalyzes in vitro reactions related to recombination process in analogous manners to E. coli recA gene product. The coding region consisted of 1170 nucleotides directing the synthesis of a polypeptide of 390 amino acids in length with a calculated molecular weight of 43,760. Amino acid composition, the sequence of seven NH2-terminal amino acids and molecular weight of the protein deduced from the nucleotide sequence were consistent with the data from the analysis of the purified uvsX protein. The nucleotide sequence and the deduced amino acid sequence were compared with those of the recA gene. Although a significant homology was not found in the nucleotide sequences, the amino acid sequences included 23% of identical and 15% of conservatively substituted residues. PMID- 2932680 TI - Successful percutaneous balloon valvuloplasty of the aortic valve in an infant. AB - Percutaneous balloon aortic valvuloplasty was attempted in an eight-month-old infant with severe aortic valve stenosis. The procedure resulted in a fall in the resting transvalvular systolic pressure gradient from 106 mmHg to 40 mmHg and no aortic regurgitation. Clinical and Doppler echocardiography findings suggest persistent improved status 3 1/2 months after the procedure. PMID- 2932681 TI - Effect of sunlight and its component wavebands on contact hypersensitivity in mice and guinea pigs. AB - Exposure of mice to UVB (280-320 nm) radiation is known to suppress the development of contact hypersensitivity (CHS) to chemicals that are applied subsequently to unirradiated skin, and this suppression is associated with the generation of suppressor lymphocytes. In this study, the systemic effect of other wavebands of nonionizing radiation on the development of CHS has been tested. Large doses of visible (greater than 400 nm) radiation produced a small but consistent systemic suppression of CHS in mice. In contrast, a large dose of UVA (320-400 nm) radiation did not suppress CHS but, rather, enhanced this immune response. Exposure of both mice and guinea pigs to sunlight produced systemic suppression of CHS. The suppression could be transferred to normal syngeneic animals by injection of splenic lymphoid cells obtained from animals that exhibited suppression, indicating that suppressor cells are associated with sunlight-induced systemic suppression of CHS. The immunomodulatory effect of sunlight was partially abrogated by a Mylar filter or prior application of a sunscreen containing para-aminobenzoic acid to the exposed skin. Thus, wavelengths mainly in the UVB portion of sunlight (295-320 nm) are responsible for sunlight-induced suppression of CHS, although wavelengths in the visible region may also play a role. PMID- 2932682 TI - [Echogenicity of the normal pancreas]. PMID- 2932683 TI - [Ultrasonic diagnosis of abdominal wall abscesses]. PMID- 2932684 TI - [A method of percutaneous angioplasty in the treatment of arteriosclerosis]. PMID- 2932685 TI - Noninvasive Doppler flowmetry for measuring regional blood flow. AB - Ultrasonic Doppler flowmetry should assume an increasingly important role in the serial evaluation of human cardiovascular physiology. The principal advantages of this method are that it (1) is noninvasive, (2) is nontraumatic, (3) provides anatomic and physiologic data, and (4) provides dynamic measurements. Nevertheless, the equally important limitations of the technique are that it (1) is difficult to apply in some subjects (ie, those who are obese or have anatomic variations), (2) requires operator skill and a thorough knowledge of human anatomy and cardiovascular dynamics, (3) has a finite spatial resolution that may compromise the measurement of small (1 mm) vessel diameters, and (4) has a finite velocity-measuring capability that will affect measurements of blood velocities outside the range of approximately 2 to 200 cm/sec. Full appreciation of the capabilities and limitations of noninvasive ultrasonic Doppler flowmetry makes possible a better understanding of the dynamic interplay of anatomy, pressure, flow, and resistance in the normal and abnormal intact human cardiovascular system. PMID- 2932686 TI - Acne vulgaris. Treatments and their rationale. PMID- 2932687 TI - The effects of treatment on target organ damage in hypertensive disease. PMID- 2932688 TI - Drug eruptions. PMID- 2932689 TI - [Acute suppurative myositis. 4 cases]. AB - Four cases of acute pyomyositis are reported. They were diagnosed at an advanced stage, and the different complementary examinations were of uneven value. The responsible pathogen was Staphylococcus aureus in 3 cases and a strain of Streptococcus in 2 cases (one patient had both germs). Cure was obtained in 3 patients, including one who required amputation; the 4th patient died. In this disease only the finding of purulent fluid at surgery or by needle aspiration has a diagnostic value. Management consists of antibiotic therapy associated with surgical drainage. PMID- 2932690 TI - [Value of the transjugular venous approach to the liver in the diagnosis of cirrhosis. 333 cases]. AB - The transjugular technique is very useful for the diagnosis of cirrhosis since it makes it possible, in one single exploratory procedure, to perform a needle aspiration biopsy (despite coagulation disorders and ascites) and to measure the porto-caval pressure gradient. In our series cirrhosis was diagnosed by liver biopsy alone in 249 out of 333 patients (77%), and the porto-caval gradient was found to be elevated in 313 patients (97%). PMID- 2932691 TI - [Fetal death caused by myocarditis and isolated congenital auriculoventricular block]. AB - A 26-year old woman gave birth, at term, to a child with isolated complete heart block. A second pregnancy was interrupted by foetal death. Among other immunological abnormalities, this young woman had an antibody resembling the anti SS-B antibody. At pathological examination the foetus' heart was found to be free of malformation but presented with subacute myocarditis associated with microcalcifications of the conductive tissue. Such findings suggest that an incipient myocarditis may either result in foetal death or lead to fibrosis of conduction pathways with isolated complete heart block. PMID- 2932692 TI - [Alpha-chain disease]. AB - The pathological and clinical features of alpha-chain disease, its immunological diagnosis, the structural abnormalities of the abnormal immunoglobulin A compared with those of proteins of gamma and mu heavy chains diseases, the course of the disease and its present treatment, the epidemiological factors involved and their influence on pathogenesis and finally, the relationship with the "Mediterranean abdominal lymphoma" or IPSID are successively described. The stress has been placed on the latest data which refine but no not modify the first description of the disease. In the same way as studies on the synthesis and structure of proteins in heavy chain diseases will provide new data on the biosynthesis of normal immunoglobulins, so the elucidation of sequential events leading from a plasmocytic stage reversible by antibiotic therapy alone to a highly malignant immunoblastic stage should improve our knowledge of the genesis of human lymphomas. PMID- 2932693 TI - [Plurifragmentary ruptures of the kidney. Wrapping by absorbable mesh]. AB - In two patients presenting with rupture of the kidney, the fragments of that organ were kept together by wrapping in a resorbable mesh after haemostasis and trimming. The post-operative period was uneventful. This method facilitates conservative renal surgery, even in cases with severe damage. PMID- 2932694 TI - [Rupture of pulmonary hydatid cysts under corticotherapy]. PMID- 2932695 TI - [Cyproterone acetate is not effective in the prevention of hereditary angioneurotic edema]. PMID- 2932696 TI - [Simultaneous detection of bronchopulmonary cancer and acute myeloid leukemia]. PMID- 2932697 TI - [Medullary thyroid cancer may take up meta-iodobenzylguanidine]. PMID- 2932698 TI - [Chronic lymphoid leukemia complicated by rectal cancer and acute myelomonocytic leukemia]. PMID- 2932699 TI - [Efficacy of low-dose cytarabine after failure of conventional chemotherapy]. PMID- 2932700 TI - [Transitory monoclonal gammopathy and Bence-Jones proteinuria in pneumonia]. PMID- 2932701 TI - [Carriage of HBs antigen in pregnant women and spread of the virus in their family]. PMID- 2932702 TI - [Polymyositis as a sequela of inactive rheumatoid arthritis]. PMID- 2932703 TI - [Monitoring of inflammation markers and rationalization of antibiotherapy in children]. PMID- 2932704 TI - [Apical hypertrophic cardiomyopathy: an element in the continuum of hypertrophic cardiomyopathies]. AB - Fourteen cases of apical hypertrophic cardiomyopathy (i.e. hypertrophy localized to the distal half of the left ventricular wall) are reported. There were 12 men and 2 women aged from 21 to 84 years. Only one of the patients presented, at first consultation, with severe functional symptoms, namely stage IV dyspnoea. ECG tracings were always abnormal, but the classical giant T waves were found in only 7 patients. In the 9 patients who had cardiac catheterization the left ventricular end-diastolic pressure was raised, and angiography showed an "ace of spades" diastolic image of the left ventricle with systolic obliteration of its tip. The distribution of parietal hypertrophy was best studied by two-dimensional echocardiography: the left ventricular apex was affected alone in 7 patients and concomitantly with the adjacent segments of the left or right ventricle in the other 7 patients. A family study showed that 3 patients had a descendant with obstructive cardiomyopathy. At a 4.6 years' follow-up the course of the disease was usually favourable. Apical hypertrophic cardiomyopathy is not a particular entity but one of different possible forms of hypertrophic cardiomyopathy. It seems to be benign in most cases. PMID- 2932705 TI - [Influence of diazepam premedication on upper digestive fiberscopy. 81 cases]. AB - Upper gastrointestinal endoscopy is routinely used to follow up patients with digestive disease. The influence of premedication with diazepam on the procedure and on patients' acceptance of a second endoscopy was evaluated in a double-blind trial conducted on 81 patients randomized to 3 types of intravenous premedication: placebo (group A, 29 patients), diazepam 5 mg (group B, 27 patients) and diazepam 10 mg (group C, 25 patients). Endoscopy was performed under unfavourable conditions (refusal or agitation) in 12, 4 and 1 patients respectively of groups A, B and C (P less than 0.02). Out of 65 patients questioned one month later, 1 (group A) sternly refused a second endoscopy, 10 accepted unreservedly (O in group A, 4 in group B, 6 in group C; P less than 0.05 between A and C) and 54 accepted reluctantly. To find out whether diazepam was beneficial by impairing memory, a memory score on duration of the procedure was established; there were no significant differences between the three groups (P less than 0.001), but they did not correlate with the patients' acceptance of a second endoscopy. It is concluded that premedication with diazepam 10 mg i.v. makes upper gastrointestinal endoscopy easier to perform and facilitates acceptance of a repeat endoscopy 1 month later. This effect is probably independent of the impairment in memory induced by diazepam. PMID- 2932706 TI - [Non-traumatic rupture of the Achilles tendon after renal transplantation]. AB - Two renal transplant recipients who had been grafted for 6 and 17 years respectively and whose transplants were perfectly well tolerated presented with non traumatic rupture of Achilles tendon. A few days to a few weeks previously, they had experienced pain in the Achilles tendons of both legs. No sign of so called systemic disease or hyperparathyroidism was present. The suspected pathogenic factors were chronic corticosteroid therapy and arteritis of the lower limbs. The case of a third renal transplant recipient showed that total rupture can be avoided if the tendon is allowed to rest during the phase of premonitory pain. PMID- 2932707 TI - [Fatal hematemesis due to erosion of a retro-esophageal right subclavian artery by an esophagogastric tube]. AB - A case of fatal haematemesis due to erosion of a retro-oesophageal right subclavian artery by a nasogastric tube is reported. In view of this exceptional but extremely serious complication, no oesophageal tube should be used in patients known to have this abnormal anatomical arrangement. Systematic treatment of aberrant subclavian arteries should perhaps be considered when it can be performed during thoracic surgery. PMID- 2932708 TI - [Melatonin]. AB - Melatonin is an indolamine synthesized from tryptophan in the pineal gland. It is regarded as "the epiphyseal hormone". Its antigonadotropic action has been demonstrated in animals, both in vitro and in vivo, together with its inhibitory effect on numerous endocrine functions and its anti-convulsive properties. Recently developed assay methods have made it possible to obtain clinical data, for the moment purely descriptive. Melatonin is present in several body fluids, such as urine, blood and cerebrospinal fluid. It is secreted in circadian cycles, with low concentrations during the day and high concentrations at night; sex has no influence on this pattern, but secretion is highest in the summer and winter and lowest in the spring and autumn. The part played by melatonin in the genesis of puberty is undetermined. Melatonin secretion appears to be mediated by the adrenergic system, since beta-blockers inhibit the nocturnal rise. However, contrary to what happens in animals, most beta-adrenergic stimulants do not increase melatonin concentrations. Abnormal concentrations or perturbations in the melatonin secretion rhythm have been demonstrated in such diseases as breast cancer, cirrhosis of the liver, Klinefelter's syndrome, Cushing's syndrome and haemochromatosis. Depressive syndromes are often associated with abnormal melatonin cycles. It has been suggested that melatonin could be used as a biological marker in cancer and psychiatric diseases, but its physiological function in man remains obscure. PMID- 2932709 TI - [Ultrasonically-guided percutaneous puncture of Wirsung's duct]. AB - A technique of ultrasonically guided percutaneous puncture of Wirsung's duct for pancreatic juice collection and radiological opacification is described. The equipment used is a linear array real-time transducer with a groove into which a metallic support provided with a guiding needle is attached. Once the depth at which the duct lies has been determined, a Chiba's needle is passed through the guiding needle and pushed up to the corresponding length. Pure pancreatic juice is then withdrawn for lactoferrin assay and a contrast medium is injected for pancreatography. PMID- 2932710 TI - [Does astasia-abasia of parietal origin exist?]. PMID- 2932711 TI - [Anginal pain caused by nifedipine: scintigraphic illustration]. PMID- 2932713 TI - [Digestive absorption of a single loading dose of sodium valproate solution. Comparison of oral and rectal routes]. PMID- 2932712 TI - [Value of mepacrine in the treatment of resistant giardiasis]. PMID- 2932714 TI - [Massive flumequine poisoning]. PMID- 2932715 TI - [Complement fractions in cord blood. Value for the neonatal detection of hereditary angioneurotic edema]. PMID- 2932716 TI - [Hypoglycemia in bronchial cancer. A rare paraneoplastic syndrome]. PMID- 2932717 TI - [Biliary embolism. A rare complication of hepatic artery embolization]. PMID- 2932718 TI - [Necrosis of the tongue disclosing Horton's disease]. PMID- 2932719 TI - [Legislation on diabetes (2)]. PMID- 2932720 TI - [Hypercalcemia in granulomatous diseases: a dysfunction of vitamin D metabolism]. PMID- 2932721 TI - [Diagnosis of undifferentiated tumors by means of monoclonal antibodies on paraffin sections]. AB - The diagnostic value of 3 monoclonal antibodies applied on to routinely processed surgical biopsies was assessed. These antibodies were directed against keratin polypeptide (KL1), epithelial membrane antigen (DAKO-EMA) and leucocyte common antigen (DAKO-LC). First, using a three-step immunoperoxidase procedure, we determined the phenotype of well differentiated carcinomas (21 cases), non Hodgkin's malignant lymphomas (44 cases), malignant histiocytoses (3 cases), melanomas (5 cases), sarcomas (6 cases) and miscellaneous tumors (16 cases). Nineteen out of the 21 carcinomas reacted with KL1 and DAKO-EMA antibodies but not with DAKO-LC. Forty out of the 44 non-Hodgkin's malignant lymphomas reacted with DAKO-LC. All these tumors were negative with KL1 antibodies but three of them, as well as 3 cases of malignant histiocytosis, expressed the epithelial membrane antigen. The value of these 3 antibodies was then assessed in the differential diagnosis of 30 undifferentiated tumors. A definite diagnosis was made in 28 cases: there were 11 undifferentiated carcinomas and 11 large cell malignant lymphomas. The phenotype of 6 tumors was highly suggestive of malignant histiocytosis, the peculiarity of which is to express both leucocyte common (DAKO LC+) and epithelial membrane antigens (DAKO-EMA+). Only two tumors did not react with these 3 antibodies. We conclude that it is now possible to determine the nature of nearly all undifferentiated tumors on paraffin-embedded biopsy specimens. PMID- 2932722 TI - [Clinical value of rapid bacteriological results in nosocomial infections. Comparison with traditional methods]. AB - With automated analysers, bacterial identification and susceptibility testing can be performed in 4-5 hours instead of 12-18 hours with conventional methods. A controlled trial was carried out in the surgical ward of a university hospital to evaluate the clinical repercussions of these rapid methods. The automated analyser reduced delays in the laboratory by about 25%, and optimizing information transfer from laboratory to ward brought the reduction up to 50%. It was found that earlier results of susceptibility testing modified prescriptions and this may be expected to result in a more rational use of antibiotics. PMID- 2932723 TI - [Vaccination of dental surgeons against viral hepatitis B]. AB - One hundred dental surgeons practising in western France were immunized against hepatitis B virus, using the same batch of HEVAC B vaccine from the Pasteur Institute. The vaccine was very well tolerated. Seroconversion at 10 m IU/ml was 94% after 3 injections and 98% after the booster dose. From a kinetic study of anti-HBs antibodies we were able to determine different levels of post immunization serological response and to classify responders as very good, good and fairly good. The effectiveness of the booster dose was manifest after 10 days. In view of the efficacy and safety of this vaccine, confirmed by other studies in sanitary personnel, we do not hesitate to recommend it to dental surgeons exposed to the disease. PMID- 2932724 TI - [Digital angiography by venous route and surgery of the renal artery ]. AB - Intravenous digital subtraction angiography was performed in 80 patients operated on for renovascular hypertension. Preoperative angiography (33 patients) was used for evaluation of the hypertensive state and provided accurate visualization of the renal arteries in two-thirds of the cases; confirmatory arteriography was necessary in one-third of the patients. Postoperative angiography was performed in 67 patients (20 of whom also had preoperative angiography) and provided excellent visualization of the reconstructed renal artery in all cases. Intravenous digital subtraction angiography is particularly useful in renal transplant patients, since stenosis of the renal artery is frequent in transplanted kidneys. PMID- 2932725 TI - [Surgical management of inguinal hernia. A reliable hernioplasty technic with long-term results]. AB - The technique described and used by the authors for the past 30 years has the advantage of a low recurrence rate, as proven by the follow-up of most patients. The fascia transversalis is repaired in a way similar to Marcy's technique but in addition the hernial sac is ligated and attached at a high level and parts of the internal and external oblique muscles are folded behind the spermatic cord. This reinforcement of the musculo-tendineous layers makes prosthetic surgery unnecessary in the vast majority of cases. PMID- 2932726 TI - [Nephritic pseudocolic and anuria, a deceptive sign of rupture of an iliac aneurysm. Diagnostic value of echography and computed tomography]. PMID- 2932727 TI - [Bidimensional echocardiography in the search for the latent origin of cerebral embolism]. PMID- 2932728 TI - [Value of computed tomography in the estimation of the extent of a fungal mycetoma]. PMID- 2932729 TI - [Varicella in the healthy adult]. PMID- 2932730 TI - [Lipo-adenomatous hyperplasia of the parathyroid glands. An unusual case of primary hyperparathyroidism]. PMID- 2932731 TI - [Malodorous leukorrhea caused by Gardnerella vaginalis vaginitis. Biochemical study of vaginal secretions]. PMID- 2932732 TI - [A case of anaphylactic shock induced by flumequine]. PMID- 2932733 TI - [Development and practical introduction of measures for improving the microbiological examination of tuberculosis patients]. PMID- 2932734 TI - [Organization of the microbiological examination of tuberculosis patients in the RSFSR]. PMID- 2932735 TI - [Means for increasing the effectiveness of bacteriological research in tuberculosis control institutions]. PMID- 2932736 TI - Molecular cloning and expression of partial cDNAs and deduced amino acid sequence of a carboxyl-terminal fragment of human apolipoprotein B-100. AB - Apolipoprotein (apo) B-100 cDNAs were identified in a human liver cDNA library cloned in the expression vector lambda gt11. The beta-galactosidase-apoB-100 fusion protein was detected by two independently produced low density lipoprotein polyclonal antisera and by three apoB-100 monoclonal antibodies that crossreact with apoB-74. It was not recognized by two apoB-100 monoclonal antibodies that crossreact with apoB-26. The longest clone, lambda B8, was completely sequenced. It contains a 2.8-kilobase DNA fragment containing the codons for the carboxyl terminal 836 amino acid residues of apo-B-100, as well as the 3' untranslated region of apoB-100 mRNA. We have thus mapped apoB-74 to the carboxyl-terminal portion of apoB-100. The deduced amino acid sequence of the cloned DNA matches the sequences of 14 apoB-100 peptides determined in our laboratory. Minor differences in amino acid sequence were noted in three of the peptides, suggesting polymorphism of apoB-100 at the protein and DNA levels. Secondary structure predictions reveal an unusual pattern for apolipoproteins, consisting of beta-structure (24%), alpha-helical content (33%), and random structure (30%). Ten amphipathic helical regions of 10-24 residues were identified. This carboxyl terminal fragment of apoB-100 is considerably more hydrophobic than other apolipoproteins with known structure. Its lipid binding regions might include stretches of highly hydrophobic beta-sheets as well as amphipathic helices. Our findings on apoB structure might be important for understanding the role of apoB 100-containing lipoproteins in atherosclerosis. PMID- 2932737 TI - Synthesis of analogs of human platelet membrane glycoprotein IIb-IIIa complex by chicken peripheral blood thrombocytes. AB - Human platelets and their phylogenetic counterparts, avian thrombocytes, play a key role in primary hemostasis. Based upon extensive studies in mammals, platelet cohesion resulting in the formation of the "hemostatic plug" is known to be mediated by the mammalian platelet glycoprotein IIb-IIIa complex in concert with fibrinogen and calcium. The immunological and biochemical technology already developed for the analyses of mammalian platelet glycoproteins has never been applied to avian thrombocytes. By indirect immunofluorescence, we now show that a polyclonal rabbit antibody specific for human glycoproteins IIb plus IIIa and the well-characterized murine monoclonal anti-IIb-IIIa complex antibody, AP2, both crossreact with IIb and IIIa analogs on intact chicken thrombocytes. By two dimensional polyacrylamide gel electrophoresis, we also demonstrate that chicken thrombocytes will incorporate [35S]methionine into several proteins, including the glycoprotein IIb and IIIa analogs during short-term (4 hr) incubation in vitro. This finding indicates that peripheral blood nucleated thrombocytes of the chicken, unlike their mammalian counterparts, retain the capacity to synthesize protein. The significance of these findings is 2-fold. First, we provide biochemical and immunological evidence that those proteins responsible for platelet cohesion in humans are structurally conserved in cells of analogous function in chickens despite the fact that these species have diverged from a common ancestor more than 200-250 million years ago. Second, we identify chicken thrombocytes as a readily available source of messenger RNA encoding numerous proteins analogous to those already characterized in human platelets, including glycoproteins IIb and IIIa. PMID- 2932738 TI - Selective loss of a subset of T helper cells in active multiple sclerosis. AB - Patients with active multiple sclerosis (MS) have a selective loss of a subset of T helper cells (Th), detectable by two-color fluorescence-activated cell sorter analysis of peripheral blood lymphocytes. By using pairs of monoclonal antibodies to the T-cell subset markers CD4 (Th) and CD8 [T suppressor/cytotoxic cell (Ts)] and the common leukocyte markers Lp220 and Lp95-150, five phenotypically distinct T-cell subsets have been identified in peripheral blood: two CD4+ Th cell subsets and three CD8+ Ts cell subsets. The frequencies and absolute numbers of these five populations were measured in patients with active and inactive MS and were compared with those in healthy age-matched controls and in patients with other neurologic diseases. A high frequency of patients with active MS (80%) had a selective reduction of one Th subset (CD4+ Lp220+) compared with normal controls (P less than 0.001) or patients with inactive MS (P less than 0.001). Three patients examined sequentially had a further loss of the Lp220+ Th subset as disease activity progressed. The proportion of two Ts subsets was also abnormal in patients with active MS, but this defect was not restricted to that group. Total Th and Ts cell frequencies and Th/Ts ratios were not significantly different between patient and normal control groups. Thus, two-color analysis of T-cell subsets may be a more sensitive indicator than conventional single-marker assays of abnormal immune status in MS patients. PMID- 2932739 TI - Use of anti-idiotypic antibodies to identify a receptor for the T-cell I-J determinant. AB - In order to identify the molecule(s) interacting with the I-J determinant on suppressor T cells, we have generated two anti-idiotypic sera: one to monoclonal anti-I-Jd antibody and one to monoclonal anti-I-Jk antibody. These antisera specifically block suppressor T-cell function in a genetically restricted manner and have no effect on helper T-cell activation. Both recognize a marker on primary monocytes and B cells but not on T cells. A myeloma cell line bearing this marker has been identified. Therefore, these antisera may recognize a molecule on cells interacting with suppressor T cells that is involved in mediating suppressor T-cell activity. The relationship between the T-cell I-J determinant and the molecule identified by the anti-idiotype may be similar to the relationship between the receptor on helper T cells and Ia molecules. PMID- 2932741 TI - The role and mechanism of action of taurine in mammalian thermoregulation. PMID- 2932740 TI - Interaction of purified type IIB von Willebrand factor with the platelet membrane glycoprotein Ib induces fibrinogen binding to the glycoprotein IIb/IIIa complex and initiates aggregation. AB - Von Willebrand factor (vWF) was purified from the plasma of a patient with type IIB von Willebrand disease (vWF from such a patient, IIB vWF) who had a normal platelet count and showed no evidence of spontaneous platelet aggregation. Large multimers of IIB vWF were absent from purified preparations and from plasma. Ristocetin-induced platelet aggregation was enhanced by purified IIB vWF. The aggregation of washed normal platelets mixed with IIB vWF (0.4 microgram/ml) required lower amounts of ristocetin than the aggregation of normal platelets mixed with the same concentrations of normal vWF. Moreover, purified IIB vWF alone induced aggregation of platelet-rich plasma at concentrations as low as 10 micrograms of IIB vWF/ml in the absence of any other agonist. Aggregation was blocked by a monoclonal antibody against the platelet membrane glycoprotein, GPIb, as well as by an anti-GPIIb/IIIa antibody. Washed platelet suspensions were promptly aggregated by IIB vWF only when fibrinogen and CaCl2 were added to the mixture. Purified IIB vWF induces the binding of fibrinogen to platelets. Such binding was blocked by the anti-GPIb monoclonal antibody as well as by the anti GPIIb/IIIa monoclonal antibody that inhibited aggregation. A second anti GPIIb/IIIa antibody, which has the property of blocking vWF but not fibrinogen binding to platelets, blocked neither aggregation nor fibrinogen binding induced by IIB vWF. These studies demonstrate that platelet aggregation is triggered by the initial interaction of IIB vWF with GPIb which is followed by exposure of fibrinogen binding sites on GPIIb/IIIa. Fibrinogen binds to these sites and acts as a necessary cofactor for the aggregation response. PMID- 2932743 TI - Reduction of nicotine-induced hyperactivity by pCPA. AB - Spontaneous locomotion of female Wistar rats was measured in six to ten minute sessions in an automated tunnel maze consisting of a central arena and six radially symmetrical angled arms. Nicotine (0.2 mg/kg subcutaneous, 20-30 minutes pretest) increased total arm visit frequency, but intrasession habituation and number of repetitive arm visits in the first six choices were not affected. pCPA (300 mg/kg IP three days pretest) reduced arm-visit frequency in nicotine-, but not in saline-treated rats; it had no effect on intrasession habituation or number of repetitions in either treatment group. 5-HTP (50 mg/kg IP 90 minutes pretest) reduced arm entry frequency in saline-, nicotine-, and pCPA-treated groups. Possible reasons for this discrepancy are discussed. PMID- 2932742 TI - Comparison between the efficacy of a single dose of secnidazole with a 5-day course of tetracycline and clioquinol in the treatment of acute intestinal amoebiasis. AB - A study was carried out in 80 patients with acute intestinal amoebiasis to compare the efficacy of treatment with a single oral dose of 2 g secnidazole and a 5-day course of 750 mg tetracycline plus 1 g clioquinol per day. Patients were allocated at random into one or other treatment group and returned for clinical assessment and microscopic examination of stools for the presence of the trophozoite or haematophagous form of Entamoeba histolytica on Days 1 to 7, 14, 21 and 28. The results showed that secnidazole produced significantly faster and more effective treatment than tetracycline/clioquinol. At the end of the follow up period, 7 of the 40 patients in the tetracycline/clioquinol group were classified as 'parasitological' failures but there were none in the secnidazole group. Moreover, there were no cases of relapse or persistence of clinical signs in the secnidazole-treated patients. Both treatments were well tolerated. PMID- 2932744 TI - Ambulation, activity level, and pain. Outcomes of a program for spinal pain. AB - The purpose of this study was to investigate changes in ambulation distance, activity level, medical care sought, and perceived pain in 49 patients with chronic spinal pain who completed an inpatient rehabilitation program. Therapy included patient education, reduction in pain medications, increased quotas for activity and ambulation, and reinforcement of nonpain behaviors. Change was measured by a 12-minute walk, an activity check list, and pain and activity self ratings. Tests were administered at admission and discharge and at one, three, and six months after discharge. Patients improved significantly in walking distance, frequency of both exercises and physical conditioning activities performed, and pain self-rating. Medical care sought decreased. Activity self rating on a 10-point scale was unchanged. This program had a positive effect on a number of factors and warrants consideration for patients with chronic spinal pain. PMID- 2932745 TI - Relationship of ankle strength and hypermobility to squatting skills of children with Down syndrome. AB - We used ankle goniometric and force measures to determine the relative contribution of hypermobility and strength to heels-down squatting (HDS) in four groups: eight children with Down syndrome, eight hypermobile children, six retarded children, and seven children with normal development. Analysis of variance and across group correlations revealed force as a major but not sole contributor to HDS; hypermobility was found not to have significant influence. Heels-down squatting may be a compensatory mechanism resulting from underdeveloped balance or irregular activation of agonist-antagonist relations around the ankle joint. PMID- 2932746 TI - Intertester reliability for selected clinical tests of the sacroiliac joint. AB - The purpose of this study was to examine the intertester reliability of 13 tests for sacroiliac joint (SIJ) dysfunction. Eight therapists examined 17 patients in two clinical settings. In each case, two therapists independently examined the patients and obtained results on all 13 of the SIJ tests. Patients with lumbosacral pain and unilateral lower extremity symptoms of a duration less than one year were examined. All the therapists had specialized in orthopedic physical therapy and had been trained in SIJ examination. Reliability was poor; 11 of the 13 tests resulted in less than 70% agreement. The two tests that relied solely on subjective patient response and imparted no information on SIJ position or mobility were within a range of 70% to 90% agreement. Our findings suggest the necessity of reviewing examination methods for the SIJ and improving reliability of clinical testing of this joint. PMID- 2932747 TI - Studies on the effects of dehydroepiandrosterone and its metabolites on attack by castrated mice on lactating intruders. AB - Triads of castrated male mice (residents) were injected each day for 2 weeks with oil vehicle or 280 nmol of dehydroepiandrosterone (D). They were tested for their attack on a lactating female (intruder) introduced in their home-cage 2,24 or 48 hr after their last injection. D significantly reduced male aggressive behavior for at least 24 hr. Other groups of castrated males were injected each day with vehicle or 280 nmol of D, dehydroepiandrosterone sulfate (DS) or androstenediol (ADIOL). D, but neither DS nor ADIOL, significantly reduced their aggressive responses to intruders. Neural levels of D, DS and testosterone (T) were measured in intact males injected with vehicle or D. The concentration of D in brain was unchanged by castration and was increased about 20 fold in D injected males. The concentration of neural T was 10 nmol/g of tissue in intact males, was almost undetectable in castrated males, and was slightly increased in D injected males. Further work will be needed to identify the steroid molecule(s) responsible for this behavioral effect of D. PMID- 2932748 TI - Physical activity of different intensities and the development of myocardial resistance to injury. AB - The conditions under which increased motor activity leads to raised resistance of the myocardium to injury were studied. Motor activity was raised by running on a treadmill; myocardial resistance was evaluated quantitatively from the extent of isoprenaline (ISO)-induced lesions. After 3 weeks of forced running (5 days a week), using an adequate daily dose, the cardiotoxic effect of ISO was reduced. Adequacy of the daily dose of exercise depended both on the distance run per day and on the rate at which the animals ran. If the training regimen was continued for further weeks, with the same daily dose of exercise, there was no significant increase in protection of the myocardium. In animals aged less than 3 months, myocardial resistance changed after higher daily doses of running than those needed in older animals. The cardioprotective effect of increased motor activity was not conditioned by increase in the weight of the myocardium. PMID- 2932749 TI - Ultrastructure of isoproterenol-induced myocardial damage in chick embryos. AB - Isoproterenol is known to cause severe myocardial lesions when given in toxic doses to adult homoiotherms. Previous studies on chick embryos revealed myocardial damage with scattered necroses in the outer layer of ventricular myocardium. The present ultrastructural study, performed on embryos 6 to 20 days old, has shown various types of cellular lesions; mainly cellular oedema, mitochondrial swelling, necroses of isolated cardiac muscle cells, fatty degeneration, accumulation of glycogen, and signs of increased proteosynthesis in the surviving muscle cells. Morphological features of the lesions differed from those which are known to be induced by isoproterenol in adult animals and seemed to depend on the stage of embryonic development. PMID- 2932750 TI - Circulatory and respiratory responses to muscular exercise in Czech and Norwegian children. AB - This paper presents a comparison between Czech and Norwegian rural healthy children with regard to the functional characteristics of the circulatory and respiratory system based upon work physiological variables and measurements of some pulmonary volumes. The study included randomised samples of boys and girls at the age of 8, 12 and 16 years, 66 Czech boys and 63 girls, 54 Norwegian boys and 57 girls. At the age of 8 years the maximal aerobic power was closely similar in both countries, but in the older age groups the Norwegian children exhibited lower physical fitness. The maximal heart rate was close to 200 min-1 on the average without any sex, age or ethnic differences. In agreement with the higher maximal aerobic power the 12 and 16 year old Czech children had lower submaximal heart rates for the same oxygen uptake than the Norwegian children. The forced vital capacity and forced expiratory volume in one second was significantly higher on the average in Czech than in Norwegian children but the latter, expressed in percent age of the former, averaged 87 to 91% without any sex, age or ethnic differences. The maximal ventilation volumes during muscular exercise reached higher values in Czech than in Norwegian children of the same age, but the mean maximal respiratory rate was close to 60 min-1, being independent of age, sex and cultural differences. During heavy exercise only 40 to 50% of the vital capacity and 45 to 55% of the forced expiratory volume were taken into account and this index of pulmonary function did not differ with sex, age or ethnic differences. PMID- 2932751 TI - Fractional cholesterol esterification rate and muscle cholesterol of healthy young men. AB - A group of fourteen healthy young male volunteers was examined to define more exactly the relations between lecithin cholesterol acyltransferase activity (LCAT), fractional cholesterol esterification rate (FER), total cholesterol (TC) and its free and esterified fractions (FC, CE) in skeletal muscles under physiological conditions. The mean values (+/- S.D.) of LCAT activity (95.4 +/- 16.3 mumol .1(-1) per hour), and FER (7.45 +/- 1.54% per hour) corresponded to published data on normolipidaemic healthy men of normal body weight. The mean value of TC in muscles was 332 +/- 83 micrograms per 100 mg of non-collagen protein, of which 14 +/- 7.4 per cent was formed by cholesterol esters. There was positive correlation between TC in muscles and age. Significant positive correlations between FER and the content of esterified cholesterol in muscles, and between FER and the proportion of esterified to total muscle cholesterol were found. These results suggest a close interrelation of cholesterol ester metabolism in the plasma and in slow pool tissues. PMID- 2932752 TI - Spectral analysis of breathing pattern in man. AB - The periodic oscillations of breathing pattern parameters were studied in 34 healthy subjects. In a three minutes' resting spirometric recording we determined the duration of inspiration, expiration and tidal volume in successive breaths and computed autocorrelation functions and power spectral density. Ten of the subjects were re-examined 2 years later. Pulmonary functions were examined in all of them. Rhythmic changes lasting several respiratory cycles were found in the breathing pattern. Rhythmic changes in the duration of inspiration, expiration and tidal volume differed from one another in the same individual. The spectrograms of the individual breathing pattern parameters in the same individual changed during a 2-year period. Despite individual differences, the power spectral density correlations in the same subject and between different subjects two years later, and the mean curves for power spectral densities, show that in all the subjects the power fell at values of 0 to 0.05 Hz and was then maintained at a roughly constant level. Differences in the spectrograms of the various parameters in the same subject can hardly be attributed to a feedback between peripheral receptors and respiratory centres. Rhythmic changes are probably of central origin. PMID- 2932753 TI - Electromyographic activity of expiratory muscles in the rat. AB - We examined the participation of expiratory muscles on breathing in the rat. The experiments were performed on 16 male rats in halothane [1.5%] or urethane [1.3 g/kg i.p.] anaesthesia. We recorded the electromyographic [EMG] activity of intercostal and abdominal muscles with a concentric needle electrode during quiet breathing, breathing against increased pressure in the airways and during the expiration reflex. In halothane anaesthesia the EMG expiratory phasic activity was observed only in internal intercostal muscles in 40% of spots examined during quiet breathing and in 58.5% when breathing against increased pressure. The EMG activity during the expiratory reflex was difficult to evaluate. In the abdominal muscles permanent EMG activity was found in 66% of trials. In urethane anaesthesia no phasic expiratory EMG activity was observed in intercostal or abdominal muscles. In abdominal muscles in 9% of trials a permanent activity was found. PMID- 2932754 TI - Influence of the time of intake of a high fat diet on gluconeogenesis. AB - Male Wistar rats aged 75 and 150 days were given high fat diet (36.5 weight % and 30 weight % fat) over a period of 14 days. The growth (PER, NPR) and utilization (NPU, LPU) parameters of protein biological value and liver phosphoenolpyruvate carboxykinase (PEPCK) activity were determined. In another experiment, the time dependence of liver gluconeogenesis enzyme (PEPCK and fructose-1,6-diphosphatase /FDP-ase/) and transaminase (alanine and aspartate aminotransferase /ALT, AST/) activities during 24 days' administration of the diet were determined. A 14 days' high fat intake had a negative effect on protein utilization in the organism of 75- and 150-day-old animals, which was more pronounced in the younger age group (a bigger drop in net protein utilization /NPU/ and greater stimulation of PEPCK activity). In 150-day-old animals the negative effect of a high fat intake was already manifested on the 6th to 10th day of the diet to the same degree as in the younger animals on the 14th day, as seen from the increase in all the enzyme activities. The paper presents findings on differences in the degree of the negative effect of a high fat intake on protein utilization with reference to age. PMID- 2932755 TI - Effect of branched chain amino acids on liver regeneration after partial hepatectomy. AB - The authors investigated the effect of the enrichment of commercial amino acid solutions with branched chain amino acids on the development of liver regeneration. Partial (65-70%) hepatectomy was performed on male Wistar rats (140 160 g body weight). Starting with the day of the operation, amino acid solutions normally used in clinical practice and the same solutions enriched with branched chain amino acids were administered by stomach tube; 24, 48 and 96 h after the operation the animals were decapitated. The onset of DNA synthesis was found to be more rapid in animals given the enriched solutions. Once regeneration had started, the stimulant effect of an increased supply of branched chain amino acid on liver regeneration was smaller. Nevertheless, even in the later phase after partial hepatectomy branched chain amino acids had a stronger stimulant effect on liver regeneration after partial hepatectomy than an energy supply in the form of sorbitol. PMID- 2932756 TI - Oestradiol and progesterone treatment and precopulatory behaviour in female rats ovariectomized at different ages. AB - The dependence of patterning of sexual behaviour was ascertained in female rats ovariectomized prepubertally as well as postpubertally on the oestradiol and progesterone treatment. As the criterion of sexual behaviour both the copulatory and precopulatory patterns were used. The hormonal treatment starting from the 5th day following ovariectomy was repeated at weekly intervals for several weeks. The females ovariectomized on the 23rd and 30th day exhibited less complete sexual patterns in comparison with the females sprayed on the 70th and the 145th day. The majority of the oldest animals exhibited, in fact, a complete sexual pattern. Incomplete sexual patterns induced in the females ovariectomized on the 30th day, but treated from the 75th day onwards suggest that exogenous ovarian hormones could not compensate for the effectiveness of endogenous hormones. The omission of hormonal treatment resulted in the rapid fall of sexual behaviour in females ovariectomized during adulthood. However, in the females ovariectomized on the 30th day a gradual decrease of sexual behaviour was found. The findings suggest that the development of sexual behavioural repertoire in female rats is not terminated at puberty, but that it proceeds together with the increasing number of oestrous cycles. PMID- 2932757 TI - Phospholipid content in the compact and spongious musculature of the carp heart (Cyprinus carpio). AB - The phospholipid content of the spongious and compact musculature of the heart of the carp (Cyprinus carpio) was compared. The content of phospholipids is higher in the spongious musculature, the greatest difference being in the content of diphosphatidylglycerol: 2.53 mumol P . g-1 wet weight in the spongious layer and 1.29 mumol P . g-1 wet weight in the compact one. In both tissues plasmalogens represent 20-27% of the tissue content of choline and ethanolamine phosphoglycerides. PMID- 2932758 TI - [Early stimulation of the handicapped and potentially handicapped children- breakthrough of a concept]. AB - The author describes the importance and value of early stimulation within the overall concept of working with handicapped persons. A brief definition and scientific arguments are given. Data on the historical development of this relatively recent field are given considerable space, as are details on concepts and organisation. Problems and weak points of the system are pointed out. From the aspect of the fact that the family is the centre of child activities, it is important to make it quite clear that early stimulation of rehabilitation must be an interdisciplinary, "open" and holistic "assistance" system for parents and families as a whole. A point worth considering is whether the system, which had so far been restricted mainly to children with handicaps in somatic field, can also be extended to cover children whose handicaps are mainly caused by psychosocial factors. PMID- 2932759 TI - Different pattern of association of beta-endorphin and cortisol responses to dextroamphetamine in postmenopausal women and young men. AB - A negative correlation between plasma beta-endorphin and cortisol responses to 0.15 mg/kg dextroamphetamine i.v. was found in a group of seven normal postmenopausal women, while the responses of the two hormones were positively correlated in nine normal young men. These results suggest that even though the adrenocorticotropic hormone (ACTH)-cortisol and beta-endorphin are usually regulated by the same mechanism (both ACTH and beta-endorphin are derived from proopiocortin), there are situations in which these systems can be associated in a different pattern. The elucidation of these situations may contribute to the understanding of regulatory mechanisms of the two systems. PMID- 2932760 TI - Age/grade differences in gifted children's attitudes toward the handicapped. PMID- 2932761 TI - Beta-endorphin, cortisol and postoperative delirium: a preliminary report. AB - A transient delirium, including hallucinations and disorientation, occurred at some time during a 48 to 72 hr postoperative period in patients recovering from elective surgery in an intensive care unit. The occurrence of delirium in these patients was associated with a significant and unusually prolonged postoperative increase in circulating levels of beta-endorphin (B-endorphin) and cortisol, and a total disruption of normal plasma circadian rhythms of B-endorphin and cortisol. Postoperative mean 24-hr plasma levels of B-endorphin and cortisol were not significantly different from preoperative baseline levels in those patients who did not exhibit post-surgical delirium. Circadian rhythms of B-endorphin and cortisol in the non-delirious patients also remained normal following surgery, although peak plasma concentrations were significantly phase-shifted to later in the day. A disruption in circadian rhythms of the endogenous opiate/hypothalamic pituitary-adrenal axis may represent an important component of post-operative psychological changes that are frequently observed in the intensive care unit setting. PMID- 2932762 TI - Neuroendocrine and psychological variables relating to post-operative psychosis after open-heart surgery. AB - Post-operative psychosis is a frequent complication after open-heart surgery. To investigate relationships between psychopathological outcome and endocrine and psychological variables, serum levels of cortisol, beta-endorphin, norepinephrine, TSH, and cholesterol were measured in 23 male patients undergoing aortic valve replacement from the day before operation (OP) until the seventh day after OP. State and trait anxiety, stress appraisal and the use of coping styles also were assessed. After OP, eight patients suffered from post-OP psychosis and nine from minor psychopathological symptoms. Post-OP psychopathology was significantly correlated with pre-OP psychopathological score as well as with state anxiety, pre- and post-OP stress, and the use of a self-controlling coping style. Serum cortisol, beta-endorphin, norepinephrine, and TSH levels were markedly elevated after OP. Cholesterol levels showed a decline. With regard to endocrine variables, the eight psychotic patients did not differ from 15 non psychotic subjects, but a subgroup of three major depressed patients had distinctly elevated levels of cortisol and norepinephrine. For all 23 patients, pre-OP cholesterol correlated with pre-OP psychopathology and post-OP depression. Furthermore, post-OP depression was significantly correlated with both post-OP cortisol and norepinephrine. These results indicate the stressful nature of the OP and suggest a multifactorial association of endocrine and psychological variables with psychiatric complications after open-heart surgery. PMID- 2932763 TI - Naloxone injections into the periaqueductal grey area and arcuate nucleus block analgesia in defeated mice. AB - In a situation of social conflict, mice that are defeated by an opponent exhibit a marked analgesia. Microinjections of naloxone (1 or 10 micrograms) into the periaqueductal grey area (PAG) or into the region of the arcuate nucleus prior to the defeat prevented the emergence of analgesia. Microinjections of morphine (5 micrograms) into these sites had previously been shown to produce profound analgesia. Mice whose adrenals were removed rapidly developed analgesia when attacked by a stimulus animal. Injection of naloxone into PAG also antagonized defeat-induced analgesia in adrenalectomized mice. These observations indicate that sites and processes in the brain rather than in the periphery are responsible for the development of analgesia in mice that are subjected to social defeat. PMID- 2932764 TI - Thermal sensory decision theory indices and pain threshold in chronic pain patients and healthy volunteers. AB - Fifty-five low back pain patients and 47 healthy volunteers judged the intensity of calibrated thermal stimuli. The method of constant stimuli yielded a pain threshold, and sensory decision theory (SDT) methods provided two independent indices of perceptual performance: discriminability, P(A), the ability to differentiate among various stimulus intensities; and report criterion, B, the tendency to use a particular response. Compared to healthy volunteers, chronic pain patients were far poorer discriminators [lower P(A)]. In addition, the chronic pain patients were more stoical (higher B) and had higher thresholds for reporting both very faint pain and pain. The poor discriminability in patients could be due to attenuation of afferent neural input. The higher criterion suggests that the thermal stimuli were perceived as being innocuous relative to their clinical pain. Comparison of SDT indices with the threshold measures revealed that the pain threshold was highly correlated to the subject's criterion for reporting pain, B, and unrelated to discriminability, P(A). PMID- 2932765 TI - Complete denture treatment for a patient with a craniofacial anomaly. PMID- 2932766 TI - A comparison of the influence of two bonding agents on the marginal seal of composite resin restorations in radicular dentin--an in vitro study. PMID- 2932767 TI - [Lymphocyte damage caused by ionizing radiation]. PMID- 2932769 TI - Percutaneous transluminal angioplasty in the region of the aortic bifurcation. The two-balloon technique with results and long-term follow-up study. AB - Percutaneous transluminal angioplasty of lesions located at the bifurcation of vessels, especially the aortic bifurcation, has been considered contraindicated because of possible occlusion or embolization of the contralateral vessel. With the evolution of angioplasty techniques and the development of new balloon catheters, these lesions can now be successfully treated with the kissing balloon technique. This technique was used to dilate 61 atherosclerotic vascular lesions in 32 patients with vascular insufficiency. The procedure was successful in 58 atherosclerotic stenoses in 30 patients. Because of the high blood flow and large size of these vessels, beneficial clinical results can be anticipated following successful dilatation. Follow-up study, extending for as long as 53 months, suggests the durability of the procedure and that the kissing balloon technique should be considered as a viable alternative to surgery in dilatable lesions of the aortic bifurcation. PMID- 2932768 TI - [Transluminal coronary angioplasty 1977-1985. Experience with 1000 interventions]. AB - Transluminal coronary angioplasty (TCA) was introduced in 1977 for dilatation of coronary stenoses. From October 1977 to December 1984 1087 procedures have been performed in Frankfurt. The mean success rate was 77% with an increase from 58% to 84% since 1977. Recurrences were seen within the first year in 15% of the patients, which could be treated successfully in a high percentage with a second TCA. Emergency bypass operations were necessary in 5.2%. Four patients (fatality rate 0.37%) died as consequence of the intervention. Within few years TCA has become an established procedure for myocardial revascularisation, with a high success rate. Major progress has been possible in the last few years due to technical developments, which are still going on. They may lead to further improvement of the results and enlargement of the indication for TCA. PMID- 2932770 TI - A comparative evaluation of cimetidine and ranitidine. PMID- 2932771 TI - When the "agency's nurse" becomes "hospital's employee". Case in point: Nation v. Weiner (701 P. 2d 1222 - AZ). PMID- 2932772 TI - The effect of atriopeptin III on membrane potential and intracellular Ca++ activity in rat glioma cells. PMID- 2932773 TI - Interaction between atrial natriuretic factor (ANF) and vasopressin (VP) in toad urinary bladder. PMID- 2932774 TI - Plasma concentration of atrial natriuretic polypeptide in chronic hemodialysis patients. PMID- 2932775 TI - Biochemical aspects of a new hormone: rat atrial natriuretic factor (rANF). PMID- 2932776 TI - The heart as an endocrine gland. PMID- 2932777 TI - Comparative studies of nicotinohydroxamic acid and neomycin on ammonia and urea metabolism in rats. AB - The effect of oral administrations of nicotinohydroxamic acid (NHA) and neomycin (NM) in ammonia and urea metabolism were investigated in the rat. NHA and NM lowered the blood ammonia level, and NHA increased urinary excretion of urea and depressed urease activity in the stomach and the colon, while NM had a smaller effect on urinary excretion of urea but depressed urease activity in the colon. PMID- 2932778 TI - Specific receptor binding of atrial natriuretic peptide to rat renal cortex. AB - Radiolabeled receptor assay (RRA) of atrial natriuretic peptide (ANP) was studied in rat kidney membranes. Binding of [125I]-ANP to membrane preparations of rat whole kidney was saturated and show a high affinity (Kd = 0.51 nM). Furthermore, renal cortex membrane had a higher affinity for ANP binding site (Kd = 0.26 nM) than renal medulla membrane (Kd greater than 100 nM). This high affinity ANP receptor site in renal cortex membrane indicated that ANP controlled the balance of water and sodium excretion due to this receptor site in the kidney. PMID- 2932779 TI - Studies on rat liver mitochondria in vitamin E-deficiency and during storage at 0 4 degrees C. AB - Isolated rat liver mitochondria, freed from microsomes and lysosomes contaminants, were maintained at 0-4 degrees C for several days using an appropriate medium and energy source. It was observed that the phospholipase A2 activity of mitochondria deficient in vitamin E is higher than in normal mitochondria, and that the presence of vitamin E in the preservation medium diminishes the phospholipase A2 activity in deficient mitochondria. In vitamin E deficient mitochondria up to 45% of phospholipids was digested by the endogenous phospholipase with little loss in the energy linked function or without considerable activation of the latent enzymes monoamine oxidase and ATPase. These results are consistent with the occurrence of phospholipids in the mitochondrial membrane which would render it more accessible to the action of phospholipase A2. PMID- 2932781 TI - Prevention and health promotion in the elderly. AB - Based on a review of the literature it can be said that a main obstacle to a rational approach to prevention and health promotion in the elderly, seems to be on the one side our lack of knowledge of what constitutes effective intervention, and on the other a feeling of great urgency--which may easily lead us astray. More basic information on factors influencing the individual rate of organ decline is needed, and controlled clinical trials of the effectiveness of different approaches to intervention are required. In the present state of things there is no need for therapeutic nihilism--important conditions causing distress and disability in old age are amenable to preventive action. PMID- 2932780 TI - Steady-state response of conscious man to small expiratory resistive loads. AB - To determine the predominant steady-state ventilatory responses to mild expiratory flow-resistive loads, we subjected 14 normal subjects to expiratory resistances of 0-10 cm H2O/L/sec (R0-R3). Breathing patterns and abdominal muscle activity (EMG) were recorded during quiet breathing, and when ventilation was augmented by dead space breathing (7 subjects) or treadmill walking (7 subjects). Expiratory loading increased expiratory time (TE), tidal volume and mean inspiratory flow rate, while decreasing inspiratory duty cycle and respiratory frequency. Minute ventilation (VI) remained constant. These load responses were most prominent during quiet breathing, and were attenuated or abolished as VI increased. Abdominal EMG was negligible during quiet breathing, increased when VI increased, but showed no consistent response to R1-R3. Thus, the principal defense against mild expiratory loads is prolongation of expiration, accompanied by enhanced inspiratory drive. Abdominal muscle expiratory activity is elicited by increasing ventilation, but occurs only sporadically with expiratory loading of the magnitude studied. PMID- 2932782 TI - Indicators of permanent institutional care. AB - This study attempts to search for early indicators of the need for referral to permanent institutional care of the chronically ill and disabled already receiving home nursing and/or home help. The study population covered 218 home nursing patients and home help clients. The follow-up period was 26 months. During the follow-up period 26 persons died and 12 were referred to permanent institutional care. Four groups of factors were studied in order to search for the early indicators: age, sex, health including functional status and housing conditions. Referral to permanent institutional care was found to be related to old age (75+ years) disorientation to weekday and year, inability to wash oneself and diagnosed dementia senilis. PMID- 2932783 TI - Problems in intervention and evaluation. A case report of a community-based rehabilitation and activation programme for the elderly and disabled. AB - A rehabilitation and activation programme for elderly and disabled home nursing patients and home help clients was launched in Posio, Finland, in 1979. The evaluation of the controlled intervention programme took two years. Only a few positive results were obtained. The self-perceived health of the elderly and disabled improved, and they used outpatient services other than physiotherapy less frequently than did the control group. The difficulties of this evaluative study were many, one problem being the low quality of outcome measures. To carry out interdisciplinary evaluative studies, the following recommendations are proposed, based on the experiences of this study: the staff in charge should have previous experience of research; an outside researcher is recommended; the connected study should not be overemphasized, in order to avoid extra pressures on the workers; the time needed to develop the routines for collecting data and writing reports should be estimated in advance and divided between the collaborators; information should be collected by many methods; possible difficulties should be anticipated; besides a local organizing body, a separate, independent and interdisciplinary supervisory team is important; any intervention should be based on the interest of several instances. PMID- 2932784 TI - [Treatment of osteoarthrosis deformans in disabled World War II veterans]. PMID- 2932785 TI - [Physical rehabilitation of rheumatic children at a rheumatic heart disease sanatorium]. PMID- 2932786 TI - [Systemic lupus erythematosus and its immunogenetic markers]. PMID- 2932787 TI - [Effect of A-cells on the activity of nonspecific T-suppressors in rheumatoid arthritis patients]. PMID- 2932788 TI - Experimental study of velocity fields in a human nasal fossa by laser anemometry. AB - Velocity fields for various cross sections of a model of a normal human nasal fossa were determined by laser anemometry, a dynamic, quantitative and non invasive technique. Velocity fields showed, in the laboratory, the very definite influence of the irregular architecture of the fossa on the characteristics of flow namely the streamlining action of the turbinates, the directional effect of the liminal valve and the greater velocity near the floor and the septum. They also allow a more precise evaluation of the flow mode than the Reynolds number. The aerodynamic effects of certain non-obstructive deformities were discussed. PMID- 2932789 TI - [Neurologic diseases, mental retardation and reduction in work capacity]. AB - The reduction of working ability, because of disease, was considered in 1,053 subjects. 21 groups of maladies were found; the neurological disease and mental retardation (MR) caused various degrees of working inability in 416 subjects, i.e. in the 39.51% of the examined population; orthopaedic changes affected the 15.57% of the patients; psychic disorders determined some inability in 8.93% of the persons. The subjects unable to work receive, by Law, an economic help. This study was limited to neurological patients and to subjects mentally retarded. The working ability was reduced by 5 types of disturbances: neuromotor pathology, mental retardation, mental deterioration and dementia, epilepsy, other neurological diseases. The neuromotor pathology affected 163 subjects; the types of symptomatology: hemiplegia; it was found in 71 patients; 62 times it was the result of cerebrovascular disease; in 4 patients it was caused by a hypoxic ischaemic pre-perinatal encephalopathy. 43 patients affected by cerebrovascular disease lost their personal autonomy, i.e. they could no longer do the activities of daily living (ADL); 7 patients lost their working ability; 12 subjects kept some ability to work. The hemiplegias which struck after 50 years of age were caused by cerebrovascular disease; paraplegia: 28 paraplegic patients have been seen; the aetiology was: poliomyelitis in 8 subjects; MS in 5 patients; ALS in 2 patients; in 13 patients the aetiology was unknown. 6 patients resulted unable to work; 8 persons kept some working ability; 14 patients lost the ability to do the ADL; tetraplegia, or double/bilateral hemiplegia, was found in 20 patients; the aetiology: poliomyelitis in 4 patients; pre-perinatal hypoxic ischaemic encephalopathy in 4 patients; 3 patients of MS; lesion of the cervical spinal cord because of breech delivery in 2 patients; the aetiology was not known in 7 persons. The ability to do the ADL was lost in 17 patients; 3 subjects kept some working ability. Double or bilateral hemiplegia (Little disease) was the model of neuromotor deficit subsequent natal encephalopathy (Infantile Cerebral Palsy, PCI); brachial plexus paralysis was only found from obstetrical (i.e. natal) origin; poliomyelitis and PKU resulted prevented as of 10 years. Mental Retardation (MR) was considered a borderline pathology between neurology and psychiatry; it included 162 subjects: in patients with severe MR a pre-perinatal hypoxic-ischaemic encephalopathy was found in 40.4% of the cases; in patients affected by moderate or light MR the same encephalopathy was found in the 11.3% of the subjects.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2932790 TI - Cavity preparation for restorative resins used with dentin adhesives. AB - The marginal adaptation of Silux used with and without previous application of different dentin adhesives was analyzed for correlation between maximum marginal contraction gap (MG) and different combinations of one or more of the following variables: area of cavity walls (A), the total area of cavity bottom and cavity walls (B), cavity depth (h), area of cavity surface (S) and cavity volume (V). The best fit to linear regression was found with MG = a + b . V/A with the mean of the correlation coefficients being 0.907. The statistical analysis showed that in order to maintain the V/A ratio at a minimum, root caries lesions should not be prepared after excavation if the retention of the restorative resin can be ensured with an effective dentin adhesive. The greatest influence on the V/A ratio was found to be exerted by the radius of the cavity bottom; variation of the radius of the surface of the cavity also influenced the V/A ratio, but to a minor degree. PMID- 2932791 TI - Follow-up of normal individuals with a positive antiglobulin test. AB - Over a period of 20 yr (1962-1982), 67 apparently fit donors at a Regional Blood Transfusion Service were found to have an unexplained positive direct antiglobulin test (DAT). During 1983, 26 were traced and re-tested. 9 still had a positive DAT only 1 of whom had developed autoimmune haemolytic anaemia. 17 had become negative though in 7 of these an autoantibody could still be detected by an enzyme technique. Unlike patients with established autoimmune disorders, the positive DAT individuals were found to have normal T cell subsets though B cells were significantly increased. PMID- 2932792 TI - Influence of faeces on the activity of antimicrobial agents used for decontamination of the alimentary canal. AB - The influence of faeces on the activity of 9 antibiotics currently used for selective decontamination of the digestive tract was studied. These in vitro findings showed that the antimicrobial activity is differently affected by the presence and concentration of faeces. Great differences in loss of activity were observed on different microorganisms. Decontaminating drugs which were found to be minimally inactivated in vitro by the presence of faeces are proven to be superior in clinical studies too. PMID- 2932793 TI - Uroflowmetry in neurologically normal children with voiding disorders. AB - A prospective study was undertaken to delineate the role of spontaneous uroflowmetry as screening procedure for functional infravesical obstruction (detrusor/sphincter dyssynergia). More than 70% of thirty-nine children referred for urinary tract infections and/or enuresis in the absence of neurological deficits underwent a complete diagnostic program including intravenous urography, voiding cystography and cystoscopy as well as spontaneous uroflowmetry, cystometry-emg and pressure-flow-emg study. The incidence of dyssynergia was 22%. However, neither the flow curve pattern nor single flow variables were able to identify children with dyssynergia. Consequently uroflowmetry seems inefficient in the screening for dyssynergia in neurological normal children with voiding disorders in the absence of anatomical bladder outlet obstruction. PMID- 2932794 TI - Trunk strength, back muscle endurance and low-back trouble. AB - The strength and endurance of the trunk muscles was studied in relation to the extent of earlier low-back trouble (LBT) in a homogeneous, and occupationally active group. Twenty-four female and 53 male postmen with an occupational seniority of more than 2 years took part in the investigation. The cumulative lifetime prevalence, the one-year and the point prevalence of LBT were 67%, 62%, and 4% in females and 55%, 52%, and 0% in males. The rates are higher than in a representative Danish population 40 years old. Anthropometrical measurements and isometric strength (MVC) in trunk flexors and extensors were recorded. The flexibility of the spine, hip and knee joints, the fingertip-floor distance, and the restricted extension of the knee were evaluated. The isometric endurance in the trunk extensors was measured by two methods: 1) prone with the unsupported trunk in a horizontal position and the legs and hips fixated to a couch; and 2) standing, at 60% MVC. The participants were divided into three groups according to the extent of previous LBT, Group I: LBT to a degree that made work impossible, Group II: LBT experienced but not to such a degree that work was hindered, and Group III: LBT never experienced. The main findings were that the isometric endurance time of the trunk extensors was shorter in group I than in II and III, while the trunk muscle strength, anthropometrical measures and joint flexibility were independent of the persons' earlier low-back episodes. Differences in the distribution of ST and FT muscle fibres are suggested as an explanation of the endurance difference.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2932795 TI - Subjective symptoms among dental technicians exposed to the monomer methyl methacrylate. AB - Dental technicians, their technical aids, and the students of the State Institute for Dental Technicians during a single academic year were surveyed for their use of the acrylic ester monomer and subjective symptoms in a questionnaire study. The population under study included all the members of the trade union in the greater Helsinki area and all specially trained technical aids in Finland. Acrylic monomers were handled daily without skin protection by 81% of the 293 respondents. Current hand dermatitis, or previous local dermatological problems, was reported by 17% of the respondents. Frequent contact with the acrylic monomer increased the rate of the self-reported dermatitis. The symptoms were spontaneously reported to be associated with the monomer by 42% of the respondents. Previously experienced allergies seemed to predispose the subjects to these irritative reactions. Other finger symptoms, eg, whitening and feelings of numbness, coldness, and pain, were reported by 25% of the respondents. Students attending the four-year technical school reported an increasing frequency of finger symptoms as their studies advanced, and in their senior year they reported the same frequency of occurrence as the qualified dental technicians. PMID- 2932796 TI - [Influence of the "aliasing" effect and the filter on the quantitative determination of the mean flow rate and flow volume per unit of time using the pulsed Doppler ultrasound method]. AB - By the pulsed doppler ultra sound the blood flow volume will be measured by a discrete time signal. The consequences which are obtained for fourier's transformation are deduced and specially the problem "aliasing" for the quantitative measurement of the flow volume per time is discussed. The influence of the different filters on the quantification of the blood flow volume per time can be demonstrated by in-vitro measurements compared with the pulsed doppler combination of Kranzbuhler (pulsed Doppler combination 8105, linear 8130) and the pulsed Doppler combination of Toshiba (pulsed Doppler combination SAL 50). PMID- 2932797 TI - Atrial natriuretic factor: a hormone produced by the heart. AB - Systematic studies on the significance of the secretory-like morphological characteristic of cardiac atrial muscle cells of mammals led to the finding that these cells produce a polypeptide hormone. This hormone, described in 1981 as atrial natriuretic factor (ANF), is diuretic (natriuretic), hypotensive, and has an inhibitory effect on renin and aldosterone secretion. Thus, ANF probably intervenes in the short- and long-term control of water and electrolyte balance and of blood pressure. Phylogenetically, ANF appears early, suggesting different functions for this peptide in accordance with each species' environment. Knowledge of the properties of the hormone should provide insights into the pathophysiology of important clinical entities and lead to the development of new pharmaceutical products. PMID- 2932799 TI - [Development and introduction of the Bed Reserve Subsystem]. PMID- 2932800 TI - [The Reference Automated Subsystem for a central first aid and emergency medical care center]. PMID- 2932798 TI - Control of directionality in lambda site specific recombination. AB - The simple relation between the substrates and products of site-specific recombination raises questions about the control of directionality often observed in this class of DNA transactions. For bacteriophage lambda, viral integration and excision proceed by discrete pathways, and DNA substrates with the intrinsic property of recombining in only one direction can be constructed. These pathways display an asymmetric reliance on a complex array of protein binding sites, and they respond differently to changes in the concentrations of the relevant proteins. The Escherichia coli protein integration host factor (IHF) differentially affects integrative and excisive recombination, thereby influencing directionality. A four- to eightfold increase in intracellular IHF coincides with the transition from exponential to stationary phase; this provides a mechanism for growth phase-dependent regulation of recombination that makes the cellular physiology an intrinsic part of the recombination reaction. PMID- 2932801 TI - [Development of public health in Turkmenistan]. PMID- 2932803 TI - [Participation of Bessarabian physicians in the revolutionary democratic movement]. PMID- 2932802 TI - [Pharmaceutical and medical workers of the Volga River region in the war years]. PMID- 2932804 TI - [Thermography in the complex examination of patients with pollinosis]. PMID- 2932805 TI - [Effectiveness of medical and hygienic information services for the population in a large city]. PMID- 2932806 TI - [Blood immunoglobulins in bronchial asthma in different climatic zones]. PMID- 2932807 TI - [Laparoscopic diagnosis of metastatic tumors of the liver]. PMID- 2932808 TI - [Emergency treatment services in a large general hospital]. PMID- 2932809 TI - [Execution of the targeted republican program "Cancer of the Lung"]. PMID- 2932810 TI - Prosthetic treatment for the patient with uncontrolled grand mal epileptic seizures. PMID- 2932811 TI - Patterns of use of inpatient pediatric dental consultation services. PMID- 2932812 TI - The geropsychiatric patient. PMID- 2932813 TI - Omphalocele and gastroschisis. AB - This brief article outlines our philosophy and management of omphalocele and gastroschisis based on personal experience with more than 200 patients. PMID- 2932815 TI - [Diagnosis and therapy of Hodgkin's disease in Freiburg in Breisgau 1964 to 1976. 1. Report of the complete collective]. AB - Between May 1964 and December 1976, 370 patients with Hodgkin's disease (CS/PSIn = 41 [11.2%], CS/PSIIn = 148 [40.2%], CS/PSIII n = 148 [40.2%], CS/PSIV n = 31 [8.4%] with different diagnoses were treated by different therapies, 250 out of them (67.5%) only by radiotherapy (local, extended, and total lymphoid irradiation), 115 (31%) by radiotherapy and chemotherapy, and five patients in stage IV (1.5%) only by chemotherapy. The first treatment divides the patients into three subgroups with significantly different prognoses: 1. a subgroup with complete remission assessed half a year after the end of therapy (n = 206 [58%]) and a healing rate of 96.2%; 2. a subgroup with partial remission (n = 62 [17.5%]) and a healing rate of 51.6%; 3. a subgroup without remission (n = 87 [24.5%]) and a healing rate of 4.2%. In case of recurrence after complete or partial remission, another complete and durable remission is achieved by subsequent therapy in about 85% of patients with preceding complete remission and statistically about 50% of patients with preceding partial remission. The overall five-year survival rate is 73.1%; a constant level of 67.3% (statistical healing rate) is observed after seven years. The following risk factors for remission have been found: the histologic manifestation lymphocytic depletion, parts of stage III, especially of type B, stage IV, and an age above 40 years and even more above 50 years. PMID- 2932814 TI - Effect of bronchodilators on the cough response to inhaled citric acid in normal and asthmatic subjects. AB - Coughing was induced in seven normal and eight asthmatic subjects by giving successive inhalations of citric acid aerosols of progressively higher concentration (range 0.5-32%). A baseline cough response was obtained on each of four experimental days, and there was no significant difference between days in this respect. Then the subjects received by inhalation either a bronchodilator (salbutamol 5 mg or ipratropium 1 mg) or placebo, in a paired double blind crossover design. A second citric acid run followed and was used for paired drug placebo comparisons. In the asthmatic subjects the cough response was diminished by both bronchodilators (p less than 0.05), and the cough threshold was significantly higher after ipratropium but not salbutamol. In normal subjects no significant effects were found. Airways calibre was assessed, by an oscillatory technique that measures the resistance of the respiratory system (Siemens Siregnost FD 5), in four of the seven normal and all eight asthmatic subjects. The mean respiratory resistance was higher in asthmatic than in normal subjects, and fell significantly after both bronchodilators. In normal subjects smaller decreases in respiratory resistance occurred, significant only with salbutamol. The simplest hypothesis which explains the results relates change in cough response to altered neuroreceptor sensitivity associated with rapid changes in bronchial calibre. PMID- 2932817 TI - Books of secrets in medieval and early modern science. PMID- 2932816 TI - [Effectiveness of sealing measures on the chewing surface of permanent teeth in clinical evaluation. II: Caries reduction]. PMID- 2932818 TI - [Notes on private libraries of German physicians of the 18th-19th centuries]. PMID- 2932819 TI - New light on the identity of "Geber". PMID- 2932820 TI - The effect of limited courses of cyclosporine on survival and immunocompetence of allogeneic bone marrow chimeras. AB - Isolator-maintained CBH/Ola (Rtlc) rats were lethally irradiated and reconstituted with spleen and bone marrow cells from fully allogeneic WAG or Wistar (Rtlu) donors. Hematopoietically reconstituted rats were treated with cyclosporine (CsA)4 as prophylaxis for graft-versus-host disease (GVHD) for periods ranging from 6 to 26 weeks. Following the termination of CsA treatment GVH reactivity developed in all recipients of allogeneic cells regardless of the duration of immunosuppression. Approximately a third of the reconstituted rats survived the post-CsA period of GVH activity; these rats carried peripheral lymphocytes and spleen cells of donor strain origin and were specifically unresponsive to donor strain skin grafts. Surviving chimeras remained healthy for long periods (up to 18 months) after transplantation, although morbidity increased slightly for rats moved to normal animal house conditions. However, all chimeras had some degree of lymphopenia and showed diminished immunological responses to extraneous antigens and third-party skin grafts. Experiments to elucidate the mechanisms by which specific tolerance was maintained in chimeras indicated that neither the deletion of host-reactive lymphocytes from the graft nor an absence of host bone-marrow-derived "stimulator" cells was responsible. It was shown that the potential GVH reactivity of normal donor strain cells was specifically suppressed in vivo (in the chimera) and that this suppression could be transferred to secondary irradiated recipients by transferring chimeric spleen cells. Attempts to demonstrate a role for suppressor cells in the maintenance of the chimeric state yielded inconclusive results. PMID- 2932821 TI - Assessment of mixed lymphocyte reactivity in human bone marrow cell cultures. AB - The use of monoclonal anti-T-cell antibodies has been proposed as a means of eliminating T cells from bone marrow inocula, and thereby avoiding graft-versus host reactions following transplantation. Since the mixed lymphocyte reaction (MLR) provides a measurement of alloreactive mature T cells, we have attempted to apply this assay to bone marrow populations before and after treatment with anti T-cell antibodies and complement. However, initial studies showed MLR to be very difficult to measure using bone marrow as a responder cell population, and a systematic analysis of the reasons for this difficulty was therefore carried out. The first major problem in performance of standard one-way MLRs using bone marrow responder cells was found to be due to the presence of numerous non-T marrow cells that maintained high levels of background proliferation. Proliferation of these populations was found to be variable during MLR culture, leading to aberrant results. This problem was overcome by removing the rapidly proliferating population of marrow cells either by density centrifugation or by susceptibility to cryopreservation and thawing. A second problem causing variability even after removal of these proliferating cells was found to be due to additional non-T cells in the marrow that responded to soluble mediators produced by peripheral blood lymphocyte stimulator cells during an MLR. Such non-T-cell stimulation was not eliminated by removal of bone marrow T cells, obscuring the results of T cell depletion of the marrow. This problem was overcome by the use of HLA-defined B cell lines as stimulators. A mixture of such lines provided a reliable stimulator source that did not produce soluble mediators capable of stimulating additional marrow cells. These refinements of MLR conditions permit a reproducible and reliable assay of bone marrow MLR, and provide a means for assessment of elimination of such alloreactive cells by monoclonal antibodies and complement. PMID- 2932822 TI - Separation of the immune response genes for LDH-B and MOPC-173. III. Evidence that the failure of B10.BASR1 to respond to LDH-B is due to an antigen-presenting cell defect. AB - Analysis of the immune response of a panel of intra-I-region recombinant mouse strains to LDH-B and MOPC-173 demonstrated that B10.ASR7 (H-2as3) and B10.BASR1 (H-2as4) failed to mount T-cell-proliferative responses to MOPC-173 and LDH-B, respectively. To localize the level of the immune response defect in the B10.BASR1 strain, B10.BASR1 macrophages were shown to be incapable of presenting LDH-B to immune responder B10.ASR7 T cells. These results were confirmed using alloreactivity-depleted and (B10.ASR7 X B10.BASR1)F1 immune T cells. Failure of these strains to respond was shown not to be the result of T cell suppression, because cyclophosphamide and anti-Lyt-2.2-plus-complement treatments did not restore responsiveness. Furthermore, B10.BASR1 macrophages were incapable of educating naive responder T cells in vitro to LDH-B--however, naive nonresponder B10.BASR1 T cells could be educated by responder macrophages to LDH-B in vitro. These results suggest that the failure of B10.BASR1 to respond to LDH-B reflects a defect at the macrophage-T cell interaction level, perhaps related to expression of unique I-A molecules created by intra-I-region recombinatorial events. PMID- 2932823 TI - [DNA replication in mammalian cells exposed to the action of physical, chemical or biological factors. IV. 5-fluorodeoxyuridine modifies the effect of hyperthermia on DNA synthesis and the survival of HeLa cells]. AB - Preliminary incubation of logarithmically growing HeLa cells with FUdR decreases an inhibitory effect of hyperthermia (43 degrees C, 1 hour) on DNA synthesis. The hyperthermia alone inhibits DNA synthesis considerably: the label in acid precipitable material accounts for 30% of control level. Preliminary incubation of the cells with FUdR (10(-6)) for 24 or 6 hours (plus 18 hours in fresh medium) decreases the effect: the label yields account for 50 or 90% of the respective control levels. A molecular weight of nascent DNA synthetized in the cells after hyperthermia or incubation with FUdR is lower than the control one but it increases rapidly during postincubation. Nucleoid of cells treated with FUdR has a sedimentation velocity which exceeds that of the control cells by more than 25%. Preliminary incubation with FUdR sensitizes the cells to hyperthermia. The effect is not believed to be associated with cells synchronization since the treatment of the cells with FUdR for 2 or 6 hours, when FUdR itself does not exert its toxic effect, brings about sensibilization of cells to hyperthermia. It is suggested that modification of the cell viability and DNA replication are related to some changes of chromatine structure induced by FUdR. PMID- 2932825 TI - [Lumbar symptoms among semi-skilled construction workers in Copenhagen]. PMID- 2932824 TI - [Lysine- and arginyl-binding sites of plasminogen domains]. AB - Hydrolysis of plasminogen permits obtaining its nine fragments. The method of differential scanning microcalorimetry reveals seven domains in plasminogen, and the affinity chromatography--three lysin- and three arginyl-binding sites. The lysin-binding sites of domains (Kringles) K1 and K4 differ in ligand specificity. Benzamidine-binding sites of domain K5 and of plasmin light chain are simultaneously arginine-binding ones. The third arginyl-binding site differing from the benzamidine-binding one is found in fragment K1-3. In the plasminogen fibrin interaction only lysin-binding sites of plasminogen take part; in the plasminogen fragments-fibrinogen fragments interaction both types of plasminogen sites participate. The heavy chain of plasmin interacts with the E-fragment of fibrinogen by the lysin-binding sites, and the light chain of plasmin interacts with D-fragment of fibrinogen by arginyl-binding sites. Sites complementary to arginyl binding sites of plasminogen are located on the DH-fragment and sites of interaction with lysin- and arginyl-binding sites--on the DL-fragment. The plasmin-fibrin interaction mediated by sites of the first four cringles is not associated with changes in the catalytic function of the active centre. Interaction of Lys-plasminogen with fibrin accelerates polymerization of the latter. The effect of Lys-plasminogen is conditioned by the lysin-binding sites. Glu-plasminogen has no effect on the polymerization process. PMID- 2932826 TI - [Percutaneous transluminal coronary angioplasty]. PMID- 2932827 TI - [Children aged 3 to 7 with Down's syndrome and their contact with the social and health services in the course of a year]. PMID- 2932828 TI - Doppler ultrasound waveforms in the fetal umbilical artery: quantitative analysis technique. AB - Doppler ultrasound waveforms from the fetal umbilical artery were analyzed by a new quantitative technique. Normal pregnancy and cases of fetal growth failure were considered. Data from the spectrum analyzer were dumped to a microcomputer, the velocity waveforms calculated and a representative waveform obtained by ensemble averaging. This curve was then fitted by a 4-parameter analytic function. We introduce R, the relative flow rate index, which measures the ratio of the average flow rate before the systolic peak to the average rate during the remainder of the cardiac cycle. In cases of fetal growth failure this ratio was significantly greater than in normal pregnancy. Other new quantities defined are the normalized systolic decay time index and the constant flow ratio. The AB ratio was also calculated. Fetal growth failure has been associated with raised placental resistance. We suggest that the fetus can initially compensate for this by increasing cardiac contractility. This can be seen by interpreting the R and AB values together. Our analysis technique enables the waveform to be efficiently described, and provides useful diagnostic information about placental function and fetal wellbeing. PMID- 2932829 TI - Doppler ultrasonic investigation of Raynaud's phenomenon: effect of temperature on blood velocity. AB - We have used spectral analysis of signals from a pulsed, range-gated Doppler ultrasonic instrument to make quantitative measurements of arterial blood flow velocity in the hands of normal subjects and persons with Raynaud's phenomenon. We measured the peak velocity during the cardiac cycle and the time integral of the velocity signal over the cardiac cycle. This latter parameter gives a sensitive indication of the degree of vasoconstriction in response to cold. Our preliminary results, based on findings in 13 subjects, suggest that Doppler ultrasound can differentiate persons with Raynaud's phenomenon from normal subjects. PMID- 2932831 TI - On the measurement of the mean velocity of blood flow over the cardiac cycle using Doppler ultrasound. AB - A number of modern duplex scanners now have facilities for determining volumetric blood flow through intact vessels. The methods these machines use to arrive at an answer must presuppose a number of conditions which may not be met in practice. This paper examines the effect that nonuniform insonation of the target blood vessel (using continuous wave or wide-gate pulsed ultrasound) has on the mean velocity, as determined using mean, root mean square (RMS) and maximum frequency processors. It is shown that for a given beam/vessel geometry the error is dependent only on the shape of the mean component of the velocity profile which, depending on the arterial site, may be flat, parabolic or intermediate. Mean processors may overestimate the mean velocity of established flow by up to 33%, but this could be turned to advantage when it is impracticable to insonate a vessel uniformly. Maximum frequency processors are of value when either plug-flow or fully established flow of low pulsatility is present in the target vessel. In the first case the mean flow is the same as the maximum flow, while in the second the mean flow is half the time averaged maximum flow, irrespective of the size and shape of the ultrasound beam. RMS processors are probably best avoided in volumetric flow measurement applications. PMID- 2932830 TI - A comparison of digital and analog methods of Doppler spectral analysis for quantifying flow. AB - Ultrasonic methods can be used for calculating flow when the mean Doppler frequency is representative of spatial average velocity. We have examined the capabilities of two commercially available methods of Doppler spectral analysis for providing measurements of spatial average velocity and flow. In a steady state flow model, Doppler audio spectra were recorded using a 5-MHz duplex scanner. Fast Fourier transform (FFT) spectral analysis was used to determine mean (M), mode (MO), and maximum (MAX) frequencies. An analog method (offset zero crossing detector = ZC) was used to determine root mean square (RMS) frequencies. The results of comparing Doppler flow estimates (QM, QMO, QMAX and QRMS) with direct flow measurements (n = 10; range = 128-1098 ml/min) were (1) QM = 0.67Q + 23 ml/min (SEE = 36 ml/min); (2) QMO = 0.96Q + 152 ml/min (SEE = 32 ml/min); (3) QMAX = 1.19Q + 171 ml/min (SEE = 23 ml/min); and (4) QRMS = 0.93Q + 76ml/min (SEE = 92 ml/min). Estimates of flow using M and RMS frequencies were adversely affected by experimental conditions likely to result in turbulence. We conclude that application of commercially available FFT determined M frequencies could result in significant errors in calculations of spatial average velocity and flow. Alternatively, FFT determined MO frequencies and ZC determined RMS frequencies resulted in accurate estimates of flow in this model. This study demonstrates the importance of evaluating the capabilities of commercially available methods of Doppler spectral analysis when using ultrasound for determining velocity and flow. PMID- 2932832 TI - Bibliography of biomedical ultrasound. No. 50. PMID- 2932834 TI - Transluminal angioplasty of the renal arteries. AB - Transluminal dilatation of renal artery stenosis for hypertension produces results similar to those of surgery for renal vascular hypertension while avoiding the major morbidity and mortality associated with surgery. In combination with intravenous digital subtraction angiography, it allows the work up and treatment of this commonly suspected disease with minimal morbidity. It is a much less expensive procedure than surgery. The previously advocated, very involved and expensive preprocedural work-up is also now unnecessary. In patients with suitable lesions and, particularly, in patients who have already experienced some renal dysfunction, percutaneous angioplasty is the technique of choice for improving both renal function and hypertension in the presence of renal artery stenosis. PMID- 2932833 TI - Doppler bubble detection and decompression sickness: a prospective clinical trial. AB - Decompression sickness in human beings exposed to high ambient pressure is thought to follow from gas bubble formation and growth in the body during return to low pressure. Detection of Doppler-shifted ultrasonic reflections in major blood vessels has been promoted as a noninvasive and sensitive indicator of the imminence of decompression sickness. We have conducted a double-blind, prospective clinical trial of Doppler ultrasonic bubble detection in simulated diving using 83 men, of whom 8 were stricken and treated for the clinical disease. Diagnosis based only on the Doppler signals had no correlation with clinical diagnosis. Bubble scores were only slightly higher in the stricken group. The Doppler technique does not appear to be of diagnostic value in the absence of other clinical information. PMID- 2932835 TI - [Topographic anatomical substantiation of the method of remuscularization of the bladder]. PMID- 2932836 TI - [Renovascular hypertension--diagnosis and therapeutic possibilities]. AB - The causes of renal vascular hypertension are outlined. These are guided by the influence on the renin-angiotensin mechanism. The so-called essential hypertension is not infrequently caused by an early nephrosclerosis, which can be diagnosed very early through electrone microscopy. Renal artery stenosis, caused by fibrodysplasia or arteriosclerosis represents a special case of renal vascular hypertension which can be treated effectively by balloon catheter dilatation. The results in 240 patients are presented where these therapeutic principles were applied. PMID- 2932837 TI - Laparoscopic examination of pelvic lymph nodes. AB - A new technique for examining pelvic lymph nodes is presented. The procedure has been used successfully on dogs. A correlative study is being undertaken to evaluate its usefulness in staging genitourinary malignancies. PMID- 2932838 TI - [100th anniversary of postgraduate training of eye doctors]. PMID- 2932839 TI - [Immediate and remote results of decompression of the celiac trunk]. AB - Results of elimination of the extravasal compression of the celiac trunk in 22 patients are analyzed. Unsatisfactory results of decompression can be explained by secondary alterations of the vessel due to the formation of scars. Thoracophrenolumbotomy in the left ninth intercostal space is recommended for performing the decompression of the celiac trunk. PMID- 2932840 TI - [Diagnosis of injuries of the diaphragm in penetrating wounds of the chest (concerning the article by Prof. V.M. Buianov et. al. "Laparoscopy in thoracoabdominal penetrating wounds")]. PMID- 2932841 TI - [Organization of surgical services for the wounded during the siege of Leningrad]. PMID- 2932842 TI - Embryo transfer in sheep under practice conditions. AB - Embryo transfer was carried out on nine Texel donor ewes, one of them on two occasions, over two breeding seasons (1980 and 1981). The donors were prepared for superovulation on the farm by two different regimens and the recipients were also synchronised on the farm of origin. Surgery was carried out on donors and recipients at a veterinary practice and the techniques of anaesthesia, surgery and embryo transfer are described. Superovulation was variable and more than two ovulations were seen in only four of the 10 ewes. Forty-one corpora lutea were produced by the 10 ewes and 27 embryos were recovered. Twenty-one embryos were transferred to recipients and 14 lambs were produced. All the 10 donors except one produced lambs themselves. The value, economics and welfare aspects of the technique of embryo transfer under practice conditions are discussed and it is concluded that the procedure should not be carried out routinely but reserved for special circumstances. PMID- 2932843 TI - Localization of the E1B proteins of adenovirus 5 in transformed cells, as revealed by interaction with monoclonal antibodies. AB - Monoclonal antibodies, one against the adenovirus type 5 E1B 55-kDa protein and one against the E1B 21-kDa protein, have been isolated and shown to recognize the same proteins as antitumor sera. Immunofluorescence studies with these monoclonal antibodies on transformed cells containing the complete adenovirus early region 1, showed that the E1B 21-kDa protein is localized in the perinuclear region. The E1B 55-kDa protein is localized in a number of different sites: a strong fluorescence is observed in a discrete body in the cytoplasm close to the nucleus, a moderate fluorescence is found in cell-cell contacts, and a weak staining in the cytoplasm. The cellular p53 antigen, which is associated with the E1B 55-kDa protein, is also found in the discrete cytoplasmic body, but not, or only in small amounts at the cell-cell contacts. However, p53 is not seen in the cytoplasm outside the discrete body, but the nucleus is weakly positive. The nature of the discrete cytoplasmic body was investigated further by electron microscopy and was found to be composed of a cluster of 8-nm filaments. The diameter of the filaments is similar to that of cytoskeletal intermediate filaments. However, staining with antibodies against the various intermediate filament proteins did not show a significant reaction with the cluster, while vimentin intermediate filaments could be demonstrated in the cells in a typical cytoskeletal pattern. It was also shown that the cluster is not composed of incorrectly aggregated tubulin. PMID- 2932844 TI - Plating efficiencies of modified lambda bio particles on temperature-sensitive hsd mutants of Escherichia coli K12. AB - Two mutants of Escherichia coli K12 that are temperature sensitive in cell growth and lambda phage production are shown to contain at least two mutations. One of the mutations in each of the isolates is in the hsd locus, and modification and restriction of lambda exhibits temperature sensitivity. One of the hsd mutations causes plaque formation by modified lambda bio particles that do not contain an intact ral gene to be temperature dependent. PMID- 2932845 TI - Mapping of a site for packaging of bacteriophage Mu DNA. AB - Mini-Mu containing variable DNA sequences at the left end, were tested for their ability to be packaged by a helper Mu phage. It was shown that a packaging site of Mu is situated between nucleotides 35 and 58 of the left end. PMID- 2932846 TI - Detection of cellular proteins associated with human adenovirus type 5 early region 1A polypeptides. AB - Antisera prepared against synthetic peptides corresponding to the amino and carboxy termini of human adenovirus type 5 (Ad5) early region 1A (E1A) proteins were used to identify polypeptides that are associated with these viral species in lytically infected KB cells. Proteins were sought which coprecipitated with E1A polypeptides using both sera and which were not recognized in extracts from mock-infected cells by either serum. Four such species were identified with apparent molecular weights of 68K, 65K, and a doublet at about 105K. A fifth species migrating with a molecular weight in excess of 250K was also identified consistently with E1A-C1 but not E1A-N1 serum. Addition of an excess of the appropriate synthetic peptide to the immunoprecipitation mixtures prevented the precipitation of all of these species. Mixing experiments demonstrated that all species were cellular proteins expressed in normal uninfected KB cells and in addition showed that an association with E1A proteins could take place in vitro. Studies carried out with the mutants pm975 and hr1 indicated that while the 105K doublet and the greater than 250K species were found with the products of both the 1.1- and 0.9-kb E1A mRNAs, 65K and 68K appeared to be primarily associated with those of the 1.1-kb mRNA. Finally, the 105K doublet and greater than 250K were shown to be phosphoproteins. These data indicated that Ad5 E1A proteins may function in a complex with cellular polypeptides which includes species of 105K, 68K, 65K, and possibly a large protein of greater than 250K. PMID- 2932847 TI - [Traditions of Soviet military medicine in the training of students of a military medical department]. PMID- 2932849 TI - [Status of the external respiratory function in patients with bronchial asthma during acclimatization at the Kislovodsk health resort]. PMID- 2932848 TI - [150th anniversary of the district military hospital of the Leningrad Military District]. PMID- 2932850 TI - [Effect of microclimate in karst caves on various hemodynamic indicators in patients with neuroses]. PMID- 2932851 TI - [The actual nutrition of the rural population of the Georgian SSR]. AB - A study was made of the factual nutrition of the rural population living in 7 regions of the Georgian SSR with different climatogeographic conditions and different working and living routines. The data obtained point to the improvement of the nutrition of the population as compared with preceding years. The caloricity of the average annual daily diet of the rural population covers energy expenditures. However, it is marked by the predominance of carbohydrates. In spite of the fact that the quota of proteins in the diet has increased, the consumption of animal proteins remains at a low level as is the use of vegetable fats. The diet of the population of all the regions under study was discovered to contain excess phosphorus and magnesium, but little ascorbic acid. Meanwhile the use of thiamine and riboflavin was established to be within normal physiological requirements. PMID- 2932852 TI - [Vitamin allowance of workers engaged in the manufacture of phosphorus]. AB - The clinical trials of a new treatment and prophylactic diet at the Chimkent phosphorus plant have shown its high efficacy as compared to an old one. This was manifested in the improvement of the workers supply with retinol, tocopherol, ascorbic and nicotinic acids. The treatment and prophylactic diet produced a more efficacious action on the vitamin supply when being a constituent part of the corrected daily nutrition that of the factual nutrition. PMID- 2932853 TI - [Rational nutrition for the pupils of choreography schools]. AB - The authors provide data obtained in the course of studying energy expenditures in choreographic students of the city of Perm depending on age and sex. Present scientifically validated food and energy requirements with regard to which approximate daily sets of foods and weekly diets for different age groups with regard to sex have been developed. It has been established that these diets tried during school year at the Perm choreographic college exert a beneficial effect on the students. PMID- 2932854 TI - Deficiency of autologous mixed lymphocyte reaction in patients with idiopathic autoimmune hemolytic anemia. AB - Alterations in the autologous mixed lymphocyte reaction (autologous MLR) have been reported in many autoimmune diseases and in diseases with a derangement of T regulatory function. We have studied autologous MLR in 10 patients with idiopathic autoimmune hemolytic anemia (IAHA). All patients had decreased autologous MLR which averaged 4,106 +/- 1,332 cpm (SEM) compared to 12,153 +/- 4,166 cpm for simultaneously studied controls. A marked decrease in phytohemagglutinin response and an imbalance of T-cell subsets were also observed. These findings suggest a possible abnormality of T immunoregulatory function in IAHA patients. PMID- 2932855 TI - [Virological and pathomorphological study of an influenzal infection in children 1982-1983]. AB - In the interepidemic period of 1982-1983, acute respiratory viral infections and pneumonias in infants in Alma-Ata were in 40.2% of cases etiologically associated with influenza infection. In the studied period in Alma-Ata and during an epidemic outbreak of influenza in Kzyl-Orda (March, 1983), two influenza A virus subtypes, H1N1 and H3N2, were in circulation. In a number of cases these subtypes were isolated from the same infants. PMID- 2932857 TI - [The state of thrombolytic therapy in acute myocardial infarct]. AB - Current experience indicates that intravenous and intracoronary thrombolysis may prove promising in improving the prognosis of acute myocardial infarction. However, because of methodological shortcomings such as insufficient numbers of patients and retarded initiation of therapy no such improvement has been documented so far. According to findings in patients and corresponding results of experimental studies, a significant improvement in myocardial function and reduction in mortality can be achieved only when reperfusion occurs within 3 hours after onset of ischaemia. With later reperfusion the results are uncertain and benefit and damage may balance each other. Recanalization of occluded coronary arteries is achieved faster and more frequently with intracoronary than with intravenous administration of streptokinase but this advantage is often offset by the loss of time before intracoronary treatment is started. Methods, technique and complications of thrombolytic therapy, as well as further management of patients are discussed. Attention is drawn to newer activators of plasminogen which are claimed to be more effective despite lesser influence on coagulation. PMID- 2932856 TI - [Balloon catheter technic and embolization--new therapeutic approaches in cerebral and spinal blood vessel malformations]. AB - Balloon catheter and embolization techniques continue to gain importance in the therapy of cerebral and spinal vascular malformations. These methods are applied either preoperatively to improve outset conditions for the operation or as an independent therapeutic measure to partially or completely bypass the malformation. So far the balloon catheter and embolization techniques are applied only within a limited field. Nevertheless, this fairly recently developed method is already indispensable in the therapeutic repertory. There are as yet no generally acknowledged principles with regard to indications for these procedures. Therefore, neurologists, neurosurgeons and neuroradiologists have to be included in the process of decision making. PMID- 2932858 TI - [Percutaneous transluminal recanalization of chronic stenoses and occlusions of peripheral arteries]. AB - It is reported on indications and results of percutaneous transluminal angioplasty using the Gruntzig- and Olbert-type balloon catheter technique. It is also referred to the expansion of PTA to the treatment of multiple obliterations in different layers with vascular surgical procedures. Today the essential indications for PTA are iliac stenoses on one or both sides, stenoses of the femoral and popliteal artery as well as short occlusions of the superficial femoral and popliteal artery of less than 10 cm. PMID- 2932859 TI - [Fibrinolytic therapy of peripheral arterial occlusive disease]. AB - Occluded arterial segments can be recanalized by fibrinolytic drugs. In addition to systemic fibrinolysis another method of thrombolytic therapy has been established: Local thrombolytic therapy is carried out by infiltration of low dose of streptokinase into the thrombotic occlusion. According to the low dose streptokinase used and the short duration of therapy local thrombolysis is applicable in patients with high risks too. Therefore the range of indications to non-surgical recanalisations could be extended. The differential therapy depends on location, pathogenesis and clinical stage of the arterial occlusion. PMID- 2932860 TI - [Results of the selectol field study in Austria]. AB - This multicenter study was initiated to assess the efficacy and safety of celiprolol in a large number of hypertensive patients. Patients received a once daily dose of 200 mg celiprolol for the first 3 weeks. If blood pressure was not lowered satisfactorily after this period, the investigator was asked to rise the dose to 300 mg celiprolol or to add a diuretic for the next 3 weeks. The study included 2694 patients, 2311 of whom were evaluable over a period of 3 weeks, 2077 over 6 weeks. On admission 10% showed isolated systolic hypertension, 38% were in WHO I, 35% in WHO II and 17% in WHO III. Hypertension was known for more than 1 year in 57%, for even more than 5 years in 28%. Concomitant diseases were diabetes mellitus, chronic obstructive airways disease, peripheral arteries disease; digitalis comedication in 211 patients. BP was lowered significantly in all degrees of severity of hypertension. There was no obvious connection between efficacy and age nor with duration of disease. Only 229 patients received 300 mg celiprolol during the second period of treatment, 223 patients got additionally a diuretic. Heart rate decreased by a mean of 8 bpm and was lowered mostly in patients with tachycardia. Patients with a heart rate of 60 bpm or below showed a slight increase in heart rate. In no case heart rate fell below 50. Side effects were rare and in most cases not serious. Treatment was discontinued due to suspected side effects in 58 patients only (2.15%). We conclude, that celiprolol is a safe and efficacious drug in the management of hypertension. PMID- 2932861 TI - [Treatment of heart failure in hypertension]. PMID- 2932862 TI - [Course of antibody titer following preventive hepatitis B vaccination and a recommendation for renewal following the use of H-B-Vax vaccines]. AB - 97% of the vaccinees developed anti-HBs independently of the applied vaccine (experimental vaccine or H-B-Vax). With the experimental vaccine the mean antibody titre was 1095 IMU/ml four weeks after third inoculation. Follow up revealed that during a period of 18 month individual antibody titres declined continuously to approximately one tenth. Therefore the duration of protection depends on the titre of anti-HBs which was measured after the third immunization. A control of the antibody titres should be performed after about 3-5 years, when the antibody titres are greater than 1000 IMU/ml 4 weeks after vaccination. But a control should be made already after about 1 1/2-3 years if the antibody titres are 200-1000 IMU/ml. Antibody titres between 100 and 200 IMU/ml should be estimated about 6-18 months later and titres between 10 and 100 IMU/ml already about 3-6 months later. We recommend an immediate revaccination for persons with anti-HBs titres below 10 IMU/ml. Serological findings in hospital staff of the University in Hamburg revealed the presence of protective antibodies in 11,6% which is due to a previous hepatitis B infection. In this cases vaccination was unnecessary. PMID- 2932863 TI - [Determination of alkali resistance by skin patch testing]. AB - 298 patients suffering from eczema were tested for alkali-resistance by means of the method according to Burckhardt-Locher (ARBL) as well as patch-testing. If ARBL revealed decreased alkali-resistance, there was a high correlation with the outcome of the patch-test of alkalis. If ARBL showed normal values, however, additional patch-testing detected reduced alkali-resistance in 42.9% of the cases. In order to make a well-founded diagnosis of alkali-resistance, we suggest to combine both methods and/or to include a control of ARBL after 24 hours as proposed by Burckhardt. PMID- 2932864 TI - [Treatment of acne vulgaris with clindamycin phosphate in dermatologic practice]. AB - In an open study, 34 male and 16 female patients suffering from mild up to severe acne vulgaris were treated with topical clindamycin-phosphate over a period of 8 weeks. In the course of treatment, 96% of the patients showed improvement. In 52% of the cases, at least 65% of the inflammatory eruptions faded or they disappeared altogether; 44% of the cases showed reduction of 30-65% of their lesions. Only 4% of the patients did not respond at all to the treatment. Separate study on the various degrees of severity of the disease revealed greater improvement of severe acne than with mild and moderate forms. On the basis of pathophysiology, these cases might be still more successfully treated by means of combined therapy with comedolytics. PMID- 2932866 TI - [Ca-dependent ATPase of the cell nuclei of the brain. Effects of etimizol]. PMID- 2932865 TI - [Embolia cutis medicamentosa following intramuscular injection of pyrazolone containing preparations]. AB - Three cases of Embolia cutis medicamentosa (Nicolau-Syndrome, E. c. m.) due to intragluteal injection of an antirheumatic containing phenylbutazone are reported. The frequency of various drugs causing Embolia cutis medicamentosa in recent literature is discussed. PMID- 2932867 TI - [Laparostomy in children]. AB - Laparotomy means leaving the abdomen open after a laparotomy. This enables the surgeon to revise the abdominal cavity regularly and to check the efficacy of the drainage without repeated damages to the abdominal wall. In adults, this method is used in cases of abdominal pathology with necrotic or infectious pathogenesis. We describe the method of laparotomy in 3 cases of paediatric surgery. It was used in cases of postoperative peritonitis and we think that laparotomy may be used in these situations, especially because there are almost no sequelae. PMID- 2932868 TI - [No correlation between suppressor cell function and disease activity in natural history studies of patients with systemic lupus erythematosus]. AB - In ten patients with systemic lupus erythematosus lymphocyte suppressor cell function was repeatedly monitored over a period of nine months. The method used is based on the finding that in vitro addition of ConA to PWM-stimulated lymphocytes activates suppressor T cells which in turn inhibit immunoglobulin synthesis. Nine of ten SLE patients exhibited significant impairment of IgG suppression but no correlation was found between the outcome of the IgG suppressor cell assay and disease activity or the treatment protocol applied. PMID- 2932869 TI - [Scanning electron microscopic studies of pre- and postnatal enamel of fluoride affected teeth]. PMID- 2932870 TI - [Variation in the sequence of the secondary dentition of the lateral teeth]. PMID- 2932871 TI - [Dependence of experimental caries in the rat on the sucrose content of the cariogenic diet]. PMID- 2932872 TI - [Development of microflora following one-step and stepwise deep caries therapy]. PMID- 2932873 TI - [Reconstruction of the alveolar process using molded and compressed spongiosa. A clinical and experimental study]. PMID- 2932874 TI - [The effect of various surface structures and environmental conditions on the electrochemical behavior of semi-precious metal and non-precious metal dental alloys]. PMID- 2932875 TI - [Pathogenesis of dental caries and periodontal diseases--the concept of progression and stagnation]. PMID- 2932876 TI - Fc and C3b receptor changes on mouse peritoneal leucocytes following stimulation with an extract of Ascaris suum. AB - Changes in IgG-Fc and IgM-C3b receptors of mouse peritoneal leucocytes after in vivo stimulation with Ascaris suum adult extract were studied. Erythrocyte IgG-Fc rosettes were found to initially be decreased with A. suum stimulated neutrophils, eosinophils and macrophages in comparison with nonstimulated cells. IgG-Fc rosettes then increased with time and remained high for a 60 min exposure time. IgM-C3b rosette formation was lower with A. suum stimulated leucocytes throughout 60 min of exposure and dropped off dramatically after 30 min. Unstimulated leucocytes formed IgM-C3b rosettes sooner and maintained them at higher levels for a longer period of time than stimulated cells. PMID- 2932877 TI - [Efficacy of a complex program for controlling influenza in a large industrial city]. AB - The epidemiological and economic effectiveness of the realization of the complex three-year (1980-1982) program for the control of influenza in Perm is shown. The coverage of 46-51% of the city population, including working people, pensioners and children, with immunization carried out with the use of live and inactivated vaccines made it possible to decrease morbidity rate 2.12 times in comparison with the average data for many years. The greatest effect was achieved at large industrial enterprises where, simultaneously with vaccination covering 90% of the employees, urgent prophylaxis with remantadin and the early treatment of influenza patients were carried out. Due to these measures the morbidity rate and the number of disability days per 100 employees decreased 3-6 times. PMID- 2932879 TI - In vitro test for detecting auto-suppressive T lymphocytes in bone marrow from patients with aplastic anemia. PMID- 2932880 TI - Suppressive lymphocytes against CFU-C in relation to therapeutic response to glucocorticoid in patients with aplastic anemia. PMID- 2932878 TI - [Characteristics of immune response regulation in viral hepatitis A and B]. AB - In 272 patients with virus hepatitis A and B the content of theophylline sensitive lymphocytes (T-suppressors) and theophylline-resistant lymphocytes (T helpers) in the peripheral blood was determined. Differences in the content of T suppressors in cases of acute virus hepatitis A and B with an equal degree of severity were revealed: at the peak of hepatitis A infection in the mild form of the disease the number of the cells was decreased, while at the peak of hepatitis B infection an increase in their number was observed in the mild and moderate forms of the disease and a decrease, in the severe form of the disease. In chronic persistent hepatitis a decrease in the content of T-suppressors and an increase in the content of T-helpers were observed, and in chronic active hepatitis (at the period of remission) and increase in the T-helpers occurred. Changes in the content of the cells of both types are not characteristic of HBsAg carriership. PMID- 2932881 TI - Reduction of the slow inward current of isolated rat ventricular cells by thiamylal and halothane. AB - The barbiturates and halothane exert a negative inotropic effect on the myocardium. A reduction in the slow inward current, carried mainly by calcium ions, is an important factor for the underlying mechanism because the calcium current during the action potential provides the calcium ions for accompanying contraction, supplies Ca ions to the sarcoplasmic reticulum for subsequent contractions, and induces Ca release from the store site. It has been suggested that reduction in the slow inward current caused by anesthetics is indicated by depression of the slow action potential of the partially depolarized myocardium. In order to assess directly the effect of anesthetics on the slow inward current, we carried out voltage clamp experiments with single isolated rat ventricular cells obtained by an enzymatic dissociation method. Thiamylal (10(-4) mol . l-1) and halothane (1%) decreased the slow inward current to 60 +/- 5% (mean +/- s.d., n = 8) and to 65 +/- 10% (mean +/- s.d., n = 8) of the control value, respectively, without changing the configuration of the current-voltage curve. The results provide further evidence for anesthetic reduction of the slow inward current of the myocardium, and suggest that the negative inotropic effect is at least partly due to the reduction in that current. PMID- 2932882 TI - Caries experience in disabled pre-school children. AB - The parents of 436 disabled pre-school children were interviewed about habits and problems relevant to dental health. The children, who represented 10 different disabling conditions, were examined and dmft registered. The purpose was to study the relationship between different background variables and caries experience. The dmft score was analyzed in accordance with several sociocultural, medical, and habitual variables, using a multiple classification analysis (MCA). The number of daily carbohydrate intakes, duration of use of nursing bottle, family income, and diagnosis were the variables with the strongest association with dmft. Children with congenital heart disease, asthma, and cystic fibrosis had a considerably higher adjusted dmft than the other diagnostic groups. The proportion of children with caries experience was higher in the present survey than in groups of Norwegian children of corresponding age. PMID- 2932883 TI - Intramuscular administration of hydroxyprogesterone caproate in patients with endometrial carcinoma. Pharmacokinetics and effects on adrenal function. AB - A radio-immunoassay for the determination of the serum concentration of hydroxyprogesterone caproate (HPC) was established. After a single intramuscular injection of 1000 mg, the mean serum level reached its maximum (44-81 nmol/l) after 2-7 days. Patients on long-term adjuvant HPC treatment (consisting of 1000 mg daily for 5 days followed by 1000 mg every 2 weeks) presented peak hormone levels 2 weeks after commencing treatment. After a drop at 5 weeks, the mean serum level slowly increased again to 130 nmol/l after 25 weeks of treatment. Patients being treated with weekly injections had significantly higher serum levels than those treated every 2 weeks. Considerable inter-individual differences were observed. The serum concentrations of HPC measured in this study compare favorably with those previously found in patients treated with medroxyprogesterone acetate. The patients on adjuvant HPC showed no significant change in the levels of cortisol, dehydroepiandrosterone sulphate, androstenedione, or estrone during the first 25 weeks of treatment. PMID- 2932884 TI - [Immune response to Trypanosoma cruzi. An approach to the pathogenesis of Chagas' disease]. AB - A very large number of people in both Americas are infected with T. cruzi. Nevertheless, only a relatively small percentage of them present clinical and pathological symptoms ascribable to this infection. The different immune reactions in Chagas' disease (American Trypanosomiasis) are reviewed and discussed here, both in their protective capacity and in their probable role in the pathogenesis of Chagas' disease clinical manifestations. Antibody responses are always present in infected subjects, and several types of specific antibodies have been demonstrated; their titers are high, more so in the acute phase of the disease. Their protective capacity in vivo has been demonstrated by several groups. T cell mediated immune responses (CMIR) have also been demonstrated in patients and experimental animals, but their presence is inconsistent and their level is generally low. Nevertheless, thymus dependent immune reactions are important in anti-T. cruzi protection, as shown by experiments in T deficient animals and also by some observations in immunodepressed patients. Antibody dependent cell mediated cytotoxicity (ADCC) and natural killer (NK) cell activity directed against T. cruzi have also been proven in vitro, but their role in vivo is still unknown. There is no doubt that the immune system is able to recognize T. cruzi antigens and to protect the host against massive infection, but the immune response is not able to eliminate all the parasites, so that chronic infection ensues: this failure in "curing" the infection may be due to the above mentioned low level of CMIR and/or to escape mechanisms evolved by the parasite. The presence of immune reactions directed against self antigens in Chagas' disease patients and in experimental models of chronic Chagas' disease is also reviewed. These reactions may be due either to self antigens released by injured cells (and would then only be an epiphenomenon), or to cross-reacting antigens common to T. cruzi and normal components of the host; in fact, several cross reactions have been proven between T. cruzi and laminin, nerve tissue antigens, etc. This would point to the possibility that autoimmune reactions play an important role in the pathogenesis of Chagas' disease clinical symptoms.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2932886 TI - The study of mechanical properties of rats lungs by whole body plethysmography. AB - A simple technic for studying the pulmonary mechanics of rats by whole body plethysmography is presented. The parameters measured were: Tidal Volume (TV); Respiratory Frequency (RF); Transpulmonary Basal Pressure (TBP); Dynamic Compliance (Cdyn); Functional Residual Capacity (FRC); Transpulmonary Pressure/Volume curve (TP/V); Forced Expiratory Volume of 1/4 second (FEV 1/4); Expiratory Reserve Volume (ERV); Inspiratory Capacity (IC); Inspiratory Reserve Volume (IRV); Forced Vital Capacity (FVC); Residual Volume (RV); Forced Expiratory Mean Flow between 100-50% (FEMF 100-50), 50-25% (FEMF 50-25) and 25-0% (FEMF 25-0) of the FVC, and Total Lung Capacity (TLC). In order to verify the accuracy of the technic, common male adult Wistar rats, in which pulmonary obstructive disease is normally expected, were first submitted to these functional tests and then to pathological examination. According to the intensity of the morphological pulmonary lesion, the rats were divided in two groups: with and without suppurative pneumopathy. The analysis of the pulmonary function data showed significant decrease of the FEV 1/4 and FEMF 50-25 and increase of the FRC and RV in the groups with pulmonary suppuration. Thus, a discriminant function could be established to characterize the two groups with 100% efficiency. It was concluded that these pulmonary function tests are a valuable and reliable tool to detect lung diseases in rats. PMID- 2932885 TI - Relationship between the rate of detergent-induced hemolysis and blood type. AB - The rate of lysis of human erythrocytes induced by the action of 7.0 microM S Dodecylthiouronium chloride in 0.15 M NaCl was studied at 37 degrees C and pH = 7.2. The Rh-negative cells were hemolyzed approximately twice as fast as the Rh positive counterparts. PMID- 2932888 TI - A bioassay method for studying factors stimulating erythropoiesis using as recipient the mouse with a functionally active erythron. AB - This novel bioassay method basically differs from the conventional plethoric mouse assay in the timing of the onset of induced polycythemia relative to the administration of the substances that are being tested. While the latter measures the regenerating action of erythropoietin at a time when erythropoiesis is virtually absent, the method here described evaluates the stimulatory action(s) required to maintain the normality of the process. This fact opens new approaches for studying factors involved in the quantitative govern of erythropoiesis in the steady state. PMID- 2932889 TI - The role of irreversibly sickled cells in reducing the osmotic fragility of red cells in sickle cell anemia. AB - The measurement of the osmotic fragility of red blood cells of 7 patients with sickle cell anemia and 5 controls was carried out for the unfractionated blood and for cells of the top and bottom layers after centrifugation. The erythrocytes from all patients with sickle cell anemia were more resistant to the osmotic lysis than normal erythrocytes, and the resistance of the bottom layer cells was greater than that of the top layer cells for all cases of sickle cell anemia. In addition, in the cases of sickle cell anemia, the bottom layer contained an elevated percentage (5.0% - 23.7%) of irreversible sickled cells, as compared to 1.3% - 3.6% in the top layer. The decreased osmotic fragility of the erythrocytes in sickle cell anemia probably results from the cell damage which accompanies repeated sickle-unsickle cycles and which reaches its maximum in the irreversibly sickled cells. PMID- 2932887 TI - Effects of tityustoxin on the rat isolated tail artery. AB - The isolated tail artery when exposed to 0.14-2.80 microM tityustoxin (a purified peptide from the venom of the scorpion Tityus serrulatus) underwent a transient contraction which was followed by a long lasting period of unresponsiveness to further additions of the toxin. Reserpine pretreatment, the addition of phentolamine, tetrodotoxin, verapamil or lowering the sodium concentration abolished the responses to the toxin. Cocaine potentiated it. Tityustoxin caused a slight leftward shift of the dose-response curves to adrenaline and norepinephrine and a large potentiation of the frequency-response curves to electrical stimulation. The latter effect was greater within the lower range of frequencies assayed, which coincide with those of the physiological discharge of sympathetic nerves. These data indicate that in the tail artery the tityustoxin acts indirectly on the smooth muscle through the release of endogenous catecholamines. Most likely, changes of the properties of the sodium channels and calcium influx are involved in this effect at the nerve endings. The potentiation of the frequency-response curves suggests that the arterial hypertension produced by the scorpion sting may result mainly from an abnormally elevated overflow of sympathetic transmitters. PMID- 2932890 TI - Distribution, number and size of different types of fibres in whole cross sections of female m tibialis anterior. An enzyme histochemical study. AB - The aim of the study was to determine the distribution, total number and size of different types of fibres in whole cross-sections of female m tibialis anterior and to compare these data with previous results obtained from male skeletal muscles as well as with data on female muscles obtained by biopsy technique. The distribution of fibre types varied within the muscle cross-sections, and the pattern was slightly different from that earlier described for male muscles (Henriksson-Larsen et al. 1983). No difference in mean fibre type occurrence was found between the left and right muscles of the females. The type 2 fibres varied in size in different muscle regions and were usually largest at the deep surface of the muscle. Both the total number and size of the muscle fibres were smaller in the female muscles than in the corresponding male muscles (Henriksson-Larsen et al. 1985a, b). This resulted in a 30-40% smaller value for the total muscle fibre area in the female muscles compared to the male muscles. PMID- 2932892 TI - Somatosensory evoked potentials in Huntington's disease. PMID- 2932891 TI - Endogenous antagonists of quinolinic acid and kynurenine as links of the defensive mechanism in epilepsy. PMID- 2932893 TI - [Program of early stimulation: fixing the attention of (mongolian) children with Down's syndrome]. PMID- 2932894 TI - Bioconversion of hemicellulosics. PMID- 2932895 TI - [Prevention of gingivitis in physically handicapped school children supervised in oral hygiene]. PMID- 2932896 TI - Cost incentives for peripheral angioplasty. AB - Hospital costs and length of stay for 86 patients with peripheral vascular disease treated by bypass or percutaneous transluminal angioplasty (PTA) were assessed. The length of stay averaged 4-4.5 times longer, and the total hospital charge was 3-3.7 times greater, for bypass than for PTA. These charges are discussed in relation to current diagnosis-related groups (DRGs) and the allowed reimbursement from the Federal Prospective Payment System. In appropriately selected patients with peripheral vascular disease, PTA should be the treatment of choice from both medical and financial points of view. PMID- 2932897 TI - Selection of balloon catheter size for percutaneous transluminal angioplasty. PMID- 2932898 TI - Relative wall thickness analysis by two-dimensional echocardiography. AB - M-mode echocardiographic relative wall thickness (RWT) has been used extensively as an index of left ventricular hypertrophy. To determine whether the more extensive tomographic sampling and enhanced spatial orientation provided by two dimensional echocardiography (2DE) might improve the value of RWT analysis, we compared 2DE and M-mode RWT in 69 subjects (19 normals, 13 with aortic stenosis, 22 with aortic regurgitation, and 15 with congestive cardiomyopathy). M-mode results correlated relatively weakly with 2DE RWT (r = 0.62 at end diastole; r = 0.81 at end systole). End-systolic M-mode values were larger than 2DE results, while end-diastolic M-mode values were generally smaller than 2DE results (both p less than 0.001). Thus, in congestive cardiomyopathy M-mode RWT was larger than 2DE end-diastolic results and therefore failed to distinguish between cardiomyopathy, aortic regurgitation, and normals. We conclude that M-mode and 2DE analysis of RWT yield disparate results. Moreover, 2DE may enhance the value of RWT in the assessment of left ventricular hypertrophy due to volume overload and cardiomyopathy. PMID- 2932899 TI - Sequential and reversible multiple vessel coronary occlusion following angioplasty. PMID- 2932900 TI - Syncope in hypertrophic cardiomyopathy. I. Association with atrioventricular block. PMID- 2932901 TI - Syncope in hypertrophic cardiomyopathy. II. Coexistence of atrioventricular block and Wolff-Parkinson-White syndrome. PMID- 2932902 TI - Primary angiographic success rates of percutaneous transluminal coronary angioplasty. AB - Three distinct periods in catheter design have been identified since the advent of percutaneous transluminal coronary angioplasty (PTCA) in 1977. In the first period PTCA was performed using a double-lumen balloon catheter that had a fixed, flexible guidewire at the tip. In the second period, an independent, steerable guidewire and the steerable catheter system were used. In the third period, low profile catheters were introduced. A total of 2,969 patients who had single vessel PTCA of a native coronary artery was separated into groups according to the period during which PTCA was performed. Introduction of the steerable catheter system was accompanied by improvement in primary success rate in PTCA attempts on the right coronary artery (78% vs 88%, p less than 0.005). Introduction of the low-profile catheter was accompanied by improved primary success in PTCA attempts on the left anterior descending coronary artery (LAD) (90% vs 94%, p less than 0.005). The percentage of PTCA attempts on the LAD decreased over the 3 periods (70% to 60% to 56%), while the percentage of attempts on the left circumflex artery increased (7% to 12% to 16%). Before steerable and low-profile catheters were used, there were significant differences in ability to reach and cross stenoses among the 3 major coronary arteries. These differences no longer exist. These results indicate that technical improvements and operator experience have made stenoses in all 3 major coronary arteries equally accessible to dilatation catheters and that primary success rates and reasons for failure in these arteries are now similar. PMID- 2932903 TI - Ischemia during angioplasty after streptokinase: a marker of myocardial salvage. AB - Although thrombolytic therapy can result in lysis of a coronary artery thrombus, salvage of myocardium as measured by enzymatic, electrocardiographic and regional wall motion evaluation has not been clearly documented. Many patients after successful reperfusion continue to experience recurrent chest pain. The presence of recurrent chest pain suggests salvaged myocardium. Controlled reocclusion of the infarct vessel with the use of coronary angioplasty may support evidence for myocardial salvage. Experience in 50 patients who underwent angioplasty was reviewed retrospectively. Sixteen of the 50 patients had electrocardiographic or clinical evidence of ischemia at the time of balloon inflation. Prospectively, all patients who underwent angioplasty after they had received streptokinase were evaluated, and 5 of 5 patients had chest pain and ST-segment elevation during balloon inflation. The development of ischemic changes during balloon catheter inflation suggests the presence of persistently viable, salvaged myocardium after successful thrombolysis. PMID- 2932904 TI - Sequential balloon technique in angioplasty of severe coronary arterial obstructions. PMID- 2932905 TI - Coronary arterial findings after accidental death immediately after successful percutaneous transluminal coronary angioplasty. PMID- 2932906 TI - Nonsurgical treatment of the superior vena cava syndrome. PMID- 2932907 TI - Balloon dilatation catheter size selection. PMID- 2932908 TI - Chemotherapy of large bowel carcinoma--fluorouracil (FU) + hydroxyurea (HU) vs. methyl-CCNU, oncovin, fluorouracil, and streptozotocin (MOF-Strep). An Eastern Cooperative Oncology Group study. AB - In this prospective randomized study of initial chemotherapy for advanced measurable metastatic large bowel carcinoma, the response rate was 6/32 (19%) for FU + HU and 5/32 (16%) for MOF-Strep; the estimated median survival is 43 weeks for both treatments. Patients who received MOF-Strep experienced substantially greater vomiting and hematologic toxicity than patients who received FU + HU (p less than 0.001). PMID- 2932909 TI - Caring and communicating. Observations on 19 Baby Doe patients. AB - Under authority of Section 504 of the Rehabilitation Act of 1973, and stimulated by the well-publicized birth of a child with Down syndrome and esophageal atresia in 1982, the US Department of Health and Human Services (HHS) has actively responded to reports of alleged discriminatory failure to care for handicapped infants. Investigators and consultants from the (HHS) Office for Civil Rights have visited hospitals and interviewed various persons. Observations made and unofficial conclusions drawn by one participant in 19 such investigations relate not only to the care provided to these children but also to elements of communication with family, hospital staff, and others. Misunderstandings, faulty interpretations, and unrealistic expectations have resulted in bitter feelings, confusion, and frank hostility. These observations reveal an immediate need for reexamination of interpersonal communications in the context of caring for these children. PMID- 2932910 TI - A subpopulation of suppressor cells in Richter's syndrome with both monocytic and T-lymphocytic characteristics. AB - We evaluated T-lymphocyte functions in the peripheral blood of a patient with B cell chronic lymphocytic leukemia after transformation to large cell lymphoma (Richter's syndrome). A subpopulation of E-rosette adherent cells were found with T-lymphocytic surface markers (OKT3+/8+/4+), monocytic characteristics (latex ingestion, nonspecific esterase staining), and suppressor activity. In contrast to the patient's nonadherent T-cells, this subpopulation suppressed PHA proliferation of autologous lymphocytes, pokeweed mitogen (PWM)-induced proliferation of normal non-T cells, and a mixed lymphocyte reaction. Further studies are warranted in patients with Richter's syndrome, in order to determine the frequency and significance of our findings. PMID- 2932912 TI - Relationship of uteroplacental blood flow to placental clearance of maternal plasma C-19 steroids: evaluation of mathematical models. AB - The concept that the placental clearance of maternal plasma dehydroepiandrosterone sulfate through estradiol formation is a function of uteroplacental blood flow in women has been disputed. We obtained data on the clearance of maternal plasma dehydroepiandrosterone through placental estradiol formation in the baboon and used these data to evaluate some mathematical models of placental clearance. Our evaluation shows that the placental clearance of dehydroepiandrosterone is proportional to uteroplacental blood flow in the baboon. PMID- 2932911 TI - Nonoperative salvage of subcutaneous hemodialysis fistulae. AB - During a 7-month study period 11 chronic hemodialysis patients presented with thrombosis of their arteriovenous grafts or fistulae. They were prospectively entered in a protocol to evaluate the efficacy of low-dose streptokinase and percutaneous angioplasty for reopening the hemodialysis access. All patients were evaluated with a fistulagram and had local, low-dose streptokinase (10,000 U/h) infused directly into the fistula, until the thrombus dissolved or for 36 h. If repeat fistulagram demonstrated stenoses, percutaneous transluminal angioplasty was attempted. 5 patients were successfully treated, and 4 have remained patent without complication for a minimum follow-up of 9 months. 4 patients had the streptokinase stopped prematurely: 1 died (myocardial infarct), 1 was operated upon (perforated diverticulum), and 2 patients had perigraft complications. There were no major complications, although minor complications were common. Significant systemic effects on the coagulation profile did not occur. The regimen of locally infused, low-dose streptokinase and percutaneous transluminal angioplasty was found to be a safe and effective alternative for the treatment of thrombosed hemodialysis arteriovenous grafts or fistulae. If this regimen is unsuccessful, it does not preclude operative revision. PMID- 2932913 TI - A sonographic sign for detection of Down's syndrome. PMID- 2932914 TI - Tear studies in ocular rosacea. PMID- 2932915 TI - Oxygen toxicity and restructuring of pulmonary arteries--a morphometric study. The response to 4 weeks' exposure to hyperoxia and return to breathing air. AB - This study describes the pulmonary vascular lesions in rat pulmonary arteries and altered right ventricular weight after 1) prolonged exposure to hyperoxia (87% O2 for 4 weeks) at ambient pressure, 2) weaning from hyperoxia to air over 7 days, and 3) return to breathing air for 2, 4, or 8 weeks. Hyperoxia for 28 days narrows the lumen of intraacinar and preacinar arteries, increasing the percent medial thickness (%MT) by reducing the external diameter and thickening medial muscle. The ratio of patent intraacinar arteries to alveoli is significantly reduced, and pulmonary vascular obstruction and obliteration is evident by electron microscopy. A higher proportion of intraacinar and preacinar arteries have muscle in their wall than in the normal lung: in alveolar wall and duct regions, the proportion of partially muscular and muscular intraacinar arteries increases at the expense of nonmuscular ones (for both regions P chi 2 less than or equal to 0.001); and in arteries associated with terminal bronchioli and bronchioli the proportion of muscular arteries increases at the expense of partially muscular ones (for both regions P chi 2 less than or equal to 0.001). Both after weaning and after return to breathing air lumen size increases; but, even after 8 weeks, the %MT remains significantly increased, and the ratio of intraacinar arteries to alveoli is less than normal. After weaning, the proportion of muscularized intraacinar and preacinar arteries is similar to that after hyperoxia. Two weeks after return to breathing air, the proportion of muscularized alveolar wall and duct arteries is greater (for both regions P chi 2 less than or equal to 0.001). Even 8 weeks after return to breathing air more arteries are muscularized than normal (for both alveolar wall and duct regions P chi 2 less than or equal to 0.001), and within the alveolar wall still more are muscularized than after hyperoxia (P chi 2 less than or equal to 0.001). Hyperoxia causes right ventricular hypertrophy, reducing the ratio of the weight of the left ventricle and septum to that of the right ventricle (P chi 2 less than or equal to 0.001). Weaning further increases the hypertrophy, the ratio being further reduced (P chi 2 less than or equal to 0.001, compared with both hyperoxia and control values). On return to breathing air the degree of hypertrophy is less, but it persists, and even after 8 weeks the ratio is still less than normal (P chi 2 less than or equal to 0.01). PMID- 2932916 TI - An anthropometric assessment of Huntington's disease patients and families. AB - An anthropometric investigation was designed to evaluate patterns of physical deterioration in Huntington's disease (HD). In this study a comprehensive set of measurements was taken including height, weight, body circumferences, skinfold thickness, and craniofacial, linear, and breadth components of the body, on 44 normal, 26 affected, and 70 at-risk individuals between 14 and 88 years of age. The anthropometric data were converted to z-scores using standards to adjust for age and sex differences. These scores were then adjusted for inter-family variation. There were significant differences among normal and affected individuals for all dimensions of body mass, as well as for several craniofacial and linear components of the body. Several significant differences were also found between normals and particular age cohorts of at-risk persons. HD gene carrier status was further assessed by factor analysis of the adjusted scores. PMID- 2932918 TI - Effect of glucose or fructose feeding on cholesterol synthesis in diabetic animals. AB - Previous studies have demonstrated that cholesterol synthesis is increased twofold in the small intestines of rats with streptozotocin-induced diabetes. The purpose of the present study was to determine the effect of adding glucose or fructose to standard rat chow on cholesterol synthesis in control and diabetic rats. In control rats a 25% glucose or fructose diet fed for 21 days markedly inhibited hepatic cholesterol synthesis in the liver. In contrast, in diabetic animals only fructose inhibited hepatic cholesterol synthesis. In both control and diabetic animals the addition of these simple sugars to the diet did not markedly alter extrahepatic cholesterol synthesis. The enhancement of small intestinal cholesterol synthesis observed in diabetic animals was present regardless of the dietary manipulations. Further studies demonstrated that the addition of smaller concentrations of fructose (10%) to standard rat chow decreased hepatic cholesterol synthesis in both control and diabetic rats. Similarly the addition of fructose to the diet of control and diabetics for a period as short as 2 days was also sufficient to inhibit hepatic cholesterol synthesis. In both control and diabetic animals, fructose feeding decreased hepatic 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity but did not alter the percentage of HMG-CoA reductase in the active form. Finally, the intestinal hypertrophy and stimulation of intestinal cholesterogenesis that are characteristic of streptozotocin-induced diabetes occurred when either glucose or fructose was the sole caloric source. PMID- 2932917 TI - A study of some genetic characteristics of the Fur and Baggara tribes of the Sudan. AB - The average inbreeding coefficients of the highly consanguineous Fur and Baggara tribes of Western Sudan were 0.04167 and 0.04450, respectively. Two hundred ninety-eight subjects from the two tribes were tested for polymorphism of hemoglobins, seven red cell enzymes, and four serum proteins. The Baggara showed a higher gene frequency of HbS and TfD and lower gene frequency of GdA and PC compared to the Fur. Both tribes showed a low gene frequency of PGM1 and high frequency of G6PD deficiency when compared to other Sudanese tribes. In spite of the high degree of inbreeding, no significant deviation from the Hardy-Weinburg equilibrium was observed in either tribe. The effects of inbreeding seem to be offset by mixing between the two tribes on Gabal Marra Plateau. The flow of the sickle gene from the Baggara into the Fur and other Sudanese tribes is discussed. PMID- 2932919 TI - Hypertrophy and coronary and collateral vascularity in dogs with severe chronic anemia. AB - The purpose of this study was to determine 1) whether a severe hypoxic stimulus could produce an increase in coronary and collateral vascularization and 2) whether minimal coronary resistance, which increases with hypertension-induced hypertrophy, decreases when hypoxia is superimposed on volume load hypertrophy. Data were obtained on 11 dogs rendered anemic to a hematocrit of 11 +/- 0.2 vol% and maintained at this level for 4 wk. Eighteen dogs with a hematocrit of 42 +/- 0.02 vol% were used as controls. After chronic anemia the coronary and collateral flows were quantitated in a beating, vasodilated, isolated heart preparation perfused solely with blood from two normal donor dogs. The following variables were significantly increased in anemia-exposed hearts compared with controls: coronary flow per gram myocardium for the left anterior descending, the circumflex, the right, and the septal arteries; ratio of total coronary flow of each vessel to body weight; and the collateral flows to each coronary vessel. Both the right and left ventricles were hypertrophied. We conclude that severe chronic anemia produces a dissociation between hypertrophy and increased minimal coronary resistance. Severe chronic anemia appears to increase vascularization of both coronary and collateral circulation probably due to tissue hypoxia. In this model coronary collateral vascularity seems to increase in the absence of a pressure difference across collaterals. PMID- 2932920 TI - Abnormal cardiac biochemistry in spontaneously diabetic Bio-Breeding/Worcester rat. AB - Diabetes produced by injection of alloxan or streptozotocin results in cardiac dysfunction in rats that is associated with lower cardiac contractile protein ATPase activity. The purpose of this investigation was to examine cardiac myosin biochemistry in the Bio-Breeding Worcester (BB/W) rat, a strain in which diabetes occurs spontaneously and closely resembles insulin-dependent diabetes in humans. Hearts from diabetic BB/W rats were studied at 1, 4, and 7 mo after the onset of diabetes and were compared with age-matched BB/W rats that were bred for resistance to diabetes. Calcium-stimulated myosin ATPase activity was significantly decreased after 4 and 7 mo of diabetes, and actin-activated myosin ATPase was significantly depressed at all time points. Differences between hearts from control and diabetic animals increased with the duration of diabetes. Closely associated with reductions in myosin ATPase activity in the diabetes was a shift in the isomyosin content from the normally predominant V1 to the V3 isoenzyme. Thus diabetes that results from genetic causes leads to depressed myosin enzymatic activity in the rat. Furthermore, since previous studies have shown that BB/W diabetic rats do not develop hypothyroidism, the present results support the view that altered thyroid function does not mediate the abnormalities in cardiac contractile proteins in diabetes. PMID- 2932921 TI - Effect of pulmonary and renal circulations on activity of atrial natriuretic factor. AB - The effect of passage through the pulmonary and renal circulation on the activity of extracted and synthetic atrial natriuretic factors was determined by monitoring the amount of the vascular relaxing activity surviving passage through the organ. When crude atrial extract was infused through isolated perfused lungs of the guinea pig, approximately 75% of its activity survived. The activity of a 23-amino acid synthetic atrial peptide was decreased 21% on passage through these lungs, but this loss of activity was not significantly different from the crude extract. Analogous experiments in vivo showed that passage through the pulmonary circulation of the dog did not alter the activity of either the crude atrial extract or of synthetic atrial peptide. In contrast to the lack of effect of the pulmonary circulation, approximately 80% of the activity of crude atrial extract and synthetic atrial peptide was removed by the isolated perfused kidney of the rabbit, and in vivo the dog kidney removed approximately 80% of the activity of both these atrial substances. By surviving transit through the pulmonary circulation, these materials exhibit a necessary property of a circulating hormone stored in the right atrium, and the fact that the renal circulation extracts most of these materials is consistent with the kidney being a target organ of this putative hormone. PMID- 2932922 TI - The concept of subcortical dementia. AB - The authors review the concept of subcortical dementia, specifically the dementia associated with Huntington's disease, Parkinson's disease, and progressive supranuclear palsy, all subcortical processes that involve deterioration of mental abilities. Subcortical dementia affords a unique opportunity to study the progressive memory loss associated with dementia because, in contrast to cortical dementias such as Alzheimer's disease, this relatively circumscribed syndrome does not involve dysfunction of language (aphasia) and perception (agnosia and apraxia). Research strategies are proposed to examine the concept of subcortical dementia, an entity that remains controversial and not well understood. The subcortical dementias may constitute a group of partially treatable forms of dementia. PMID- 2932923 TI - [Insufficiency of the luteal phase]. PMID- 2932925 TI - [Chlamydia in inflammatory diseases of the urogenital organs in women]. PMID- 2932924 TI - [Diagnosis and treatment of genital candidiasis]. PMID- 2932927 TI - [Use of vibration massage in the complex treatment of acute inflammatory processes in the female internal genital organs]. PMID- 2932928 TI - [Clinico-pathophysiological and therapeutic aspects of exacerbation of chronic salpingo-oophoritis]. PMID- 2932926 TI - [Chlamydia in the etiology of inflammatory diseases of the female genital organs]. PMID- 2932929 TI - [Status of nonspecific and immunological reactivity in patients with exacerbation of chronic salpingo-oophoritis]. PMID- 2932930 TI - [Methodological substantiation of the principles of treatment of chronic inflammatory diseases of the uterus and adnexa uteri]. PMID- 2932931 TI - [Effectiveness of health resort treatment of patients with chronic nonspecific salpingo-oophoritis]. PMID- 2932932 TI - [Status of the breasts after reflexotherapy of chronic recurrent salpingo oophoritis]. PMID- 2932933 TI - [Treatment of endocervicitis and chronic inflammation of the adnexa uteri by helium-neon laser irradiation]. PMID- 2932934 TI - [Incidence and characteristics of the course of chronic nonspecific endometritis in infertile women]. PMID- 2932935 TI - [Value of roentgenological methods in the diagnosis of tuberculosis of the female genital organs]. PMID- 2932936 TI - [Status of immunological and nonspecific reactivity in patients with acute renal failure in obstetrical and gynecological pathology]. PMID- 2932937 TI - [Peroxidation of serum lipids in different phases of normal menstrual cycle]. PMID- 2932939 TI - [Current principles of regulation of the reproductive function in women]. PMID- 2932938 TI - [Experience with using a Czechoslovakian electroanalgesic apparatus "Analgonic-1" in the treatment of climacteric and post-castration syndromes]. PMID- 2932940 TI - [Experience in using intrauterine contraceptive devices by women with chronic pyelonephritis]. PMID- 2932941 TI - [Vacuum-aspiration of uterine contents after a missed menstrual period]. PMID- 2932942 TI - [Personal method of the surgical treatment of uterine and vaginal wall prolapse]. PMID- 2932943 TI - [A method of examination of organs of the small pelvis during laparoscopy]. PMID- 2932945 TI - [Subcutaneous provocation tuberculin test used in the tuberculosis department of the Amur tuberculosis dispensary]. PMID- 2932944 TI - [Laparoscopic diagnosis of diseases of the female internal genital organs]. PMID- 2932946 TI - [Tuberculosis in adenomyosis of the uterine body]. PMID- 2932947 TI - [Treatment and prevention of colpitis (report 2)]. PMID- 2932948 TI - [Current theories on the etiology and pathogenesis of chronic inflammatory diseases of the female genital organs]. PMID- 2932949 TI - [Labor induction by electrostimulation of the uterus]. PMID- 2932950 TI - [Labor induction and stimulation with prostaglandins]. PMID- 2932951 TI - [Correction of uterine contractile function in uncoordinated labor]. PMID- 2932952 TI - [Transcutaneous electroneural stimulation in labor analgesia]. PMID- 2932954 TI - [Characteristics of the clinical picture, hemostatic system and procedures for managing pregnancy and labor in premature detachment of a normally situated placenta]. PMID- 2932955 TI - [Anesthesiological support for cesarean section in premature detachment of the normally situated placenta]. PMID- 2932953 TI - [Gas exchange indices of parturients and newborn infants undergoing drug analgesia in labor]. PMID- 2932956 TI - [Management of pregnancy, labor and the puerperium in women with a history of eclampsia]. PMID- 2932957 TI - [Importance of peripheral and local immunity indices in the early diagnosis of endometritis following cesarean section]. PMID- 2932958 TI - [Basis for the use of immunodepressants in treating women suffering from miscarriages]. PMID- 2932959 TI - [Pathogenesis and correction of disorders of the sympathetic-adrenal and immune systems in abortion]. PMID- 2932960 TI - [Conservative procedure in managing premature labor complicated by premature fetal membrane rupture]. PMID- 2932961 TI - [Prevention of complications after a cesarean section by temporary delimitation of the abdominal cavity]. PMID- 2932962 TI - [Diagnostic importance of autonomic tests in the prognosis of labor activity]. PMID- 2932963 TI - [Uterine electrostimulation as a method of decreasing hemorrhage during cesarean section]. PMID- 2932964 TI - [Anesthesiological support for technically complex cesarean section operations]. PMID- 2932965 TI - [Serum immunoglobulin concentration and neutrophil phagocytic activity of puerperae following cesarean section]. PMID- 2932966 TI - [Characteristics of local immunity and microbial contamination of the birth canal in puerperae after cesarean section]. PMID- 2932967 TI - [Possibilities of regulating uterine contractile function with adrenergic and cholinergic agents in an experiment]. PMID- 2932968 TI - [Clinical aspects and diagnosis of a miscarriage of herpetic etiology]. PMID- 2932969 TI - [Characteristics of labor and perinatal pathology in multiple pregnancy]. PMID- 2932971 TI - [Trophoblastic beta l-glycoprotein in the diagnosis and prognosis of prolonged pregnancy]. PMID- 2932970 TI - [Functional synergism of beta-adrenomimetics and seduxen during action on the uterine contractile function in an experiment]. PMID- 2932972 TI - [Prognostic significance of HLA system antigens in pathological pregnancy]. PMID- 2932973 TI - [von Willebrand's disease and pregnancy]. PMID- 2932974 TI - [The blood kallikrein-kinin system in physiological pregnancy and labor]. PMID- 2932975 TI - [Labor stimulation by intravenous oxytocin]. PMID- 2932976 TI - Selective removal of heparan sulfate chains from proteoheparan sulfate with a commercial preparation of heparitinase. AB - Procedures employing the commercial preparation of heparitinase were developed for isolating a protein-enriched core molecule from proteoheparan sulfate by selective removal of the heparan sulfate chains. Treatment of proteoheparan sulfate with the enzyme preparation caused seriously extensive degradation owing to the presence of proteolytic activity in the enzyme preparation. This effect could be avoided by using a series of protease inhibitors which prevented proteolytic degradation with less significant effect on the heparitinase activity. Application of the procedures to a purified preparation from the Engelbreth-Holm-Swarm tumor yielded a single protein-enriched core fraction with a molecular weight of approximately 450,000, as ascertained by sodium dodceyl sulfate-gel electrophoresis. PMID- 2932977 TI - Spaced serial section analysis of the avian muscle spindle. AB - Muscle spindle ultrastructure of the extensor digitorum communis of pigeons was studied using spaced serial sections. The intrafusal fibers extended well beyond the ensheathing capsule, after which they became disoriented and often fused with each other before terminating on the connective tissue of extrafusal fibers. Several extracapsular fibers contained macrofibrils which were about 0.1 micron in diameter and contained several dozen smaller (10 nm) subunits. Intrafusal fibers commonly formed close attachments with one another for short or extended (240 micron) lengths. A basal lamina was absent between regions of pairing, and a myosatellite cell lay at the border of the coupled region. Several fibers could be coupled together in a single cross section; fibers coupled together, separated, and either recoupled or became associated with other fibers along the length of a spindle. Profiles of sensory terminals and sensory satellite cells alternated to form a smooth-contoured surface over most of the fiber cross section in the equatorial region. The sensory terminals contained many mitochondria, lysosomes, and clear and dense core microvesicles. Both the terminals and sensory satellite cells formed desmosomelike junctions with the intrafusal fiber. A crescentic collagen sheath covered that portion of the fiber cross section containing the sensory terminal-satellite cell complex. Inner capsule cells surrounded the entire assembly in the equatorial region. The basal lamina thicknesses differed over the naked intrafusal fiber compared to that portion covered by the sensory terminal or sensory satellite cell. The thickness was more than doubled over the latter regions, indicating that the basal lamina over these areas was a product of the fused intrafusal fiber and sensory terminal and/or sensory satellite cell basal laminae. These are discussed in terms of intrafusal fiber degeneration and regeneration. PMID- 2932978 TI - [Congenital fistula of the raphe penis]. AB - One case of a congenital fistula of the raphe penis with gonorrhoea is reported. In this case spectinomycin seemed to fail in therapy, because pus was still remaining in the fistula, but not in the urethra. As the antibiotic resistogram did not prove our assumption, we tried the double dose and succeeded in killing the bacteria. PMID- 2932980 TI - Magic bullets, science, and medicine. PMID- 2932979 TI - Central serotonin depletion: effect on blood pressure during anesthesia. AB - Serotonin (5-HT) in the central nervous system has been implicated in blood pressure control in both normotensive and hypertensive states. Parachlorophenylalanine (PCPA) depletes 5-HT in the central nervous system. Normotensive Wistar rats, Wistar rats made hypertensive by renal artery clipping (RHR), and spontaneously hypertensive rats (SHR) were depleted of central serotonin by the administration of PCPA. Mean arterial blood pressure (MAP), heart rate (HR), and plasma norepinephrine (NE) levels were measured in rats both before and after they were administered anesthesia with enflurane. Blood pressure was further decreased by the administration of saralasin, a competitive inhibitor of angiotensin II. Principal results are as follows. Central 5-HT was depleted by 70% or more with PCPA. In general, brain catecholamines were not altered by this treatment. No consistent pattern of change in MAP, HR, or plasma NE was observed for Wistar rats, RHR, or SHR during an awake control period in rats treated with PCPA compared with rats treated with vehicle. However, during enflurane anesthesia or enflurane anesthesia with saralasin, MAP, HR, and plasma NE were significantly greater in Wistar rats and RHR treated with PCPA compared to similar groups treated with vehicle. This was not observed in SHR: MAP, HR, and plasma NE were similar to vehicle-treated SHR. Nonsignificant changes in plasma epinephrine, plasma renin activity, or arterial blood gas tensions could not explain the differences seen in Wistar rats, RHR, or SHR. Central serotonin plays an important role in cardiovascular control during anesthesia with enflurane in Wistar rats but does not appear to play a dominant role in SHR. PMID- 2932982 TI - The cerebral effects of pancuronium and atracurium in halothane-anesthetized dogs. AB - Pancuronium decreases the minimal alveolar anesthetic concentration (MAC) of halothane in humans, while atracurium has a metabolite, laudanosine, which is a known cerebral stimulant. To determine if these muscle relaxants significantly alter cerebral function, their effects on cerebral metabolic rate (CMRo2), cerebral blood flow (CBF), intracranial pressure (ICP), EEG, and the cerebral energy state were studied in halothane-anesthetized dogs. Group A dogs (n = 6) were maintained at 0.86% end-expired (1.0 MAC) halothane. Thereafter, a sequence of 1) pancuronium 0.1 mg . kg-1; 2) reversal of neuromuscular blockade with neostigmine plus glycopyrrolate; and 3) pancuronium 0.2 mg . kg-1 produced no changes in CMRo2, CBF, ICP, or EEG. Group B dogs (n = 6) also were maintained at 0.86% end-expired halothane and received the following in sequence: 1) atracurium 0.5 mg . kg-1; 2) reversal of neuromuscular blockade with neostigmine plus glycopyrrolate; 3) atracurium 1.0 mg . kg-1; and 4) atracurium 2.5 mg . kg-1. There were no changes in CMRo2, CBF, or ICP; EEG evidence of cerebral arousal occurred in only one dog with the final dose of atracurium. Group C dogs (n = 6) received tetracaine spinal anesthesia and the minimal halothane concentration (mean +/- SE = 0.69 +/- 0.03% end-expired) that would maintain an "anesthetic" EEG pattern. Each Group C dog received the following in sequence: 1) atracurium 1.0 mg . kg-1, and 2) atracurium 2.5 mg . kg-1. EEG evidence of cerebral arousal occurred in all six Group C dogs. Arousal was not accompanied by significant increases in CBF, CMRo2, or ICP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2932981 TI - Laudanosine (a metabolite of atracurium) increases the minimum alveolar concentration of halothane in rabbits. AB - The authors hypothesized that laudanosine, a metabolite of atracurium and a central nervous system stimulant, might increase the minimum alveolar concentration (MAC) of halothane. An initial study in five rabbits anesthetized with halothane used a two-compartment model to produce estimates of pharmacokinetic variables for laudanosine. These estimates were used to determine the rates of infusion that would produce steady state plasma concentrations of laudanosine of approximately 200, 400, and 800 ng . ml-1. Subsequent infusion of laudanosine in eight rabbits produced mean (+/- SD) steady state plasma concentrations of laudanosine of 234 +/- 56, 457 +/- 66, and 873 +/- 105 ng . ml 1. The control value for MAC of halothane was 1.08 +/- 0.28%. At the lowest steady state plasma laudanosine concentration, MAC did not significantly differ from control (MAC = 1.15 +/- 0.23%, P less than 0.1). However, at 457 and 873 ng . ml-1, laudanosine significantly increased the MAC of halothane by 23% and 30%, respectively. Infusion with saline in two additional rabbits did not affect MAC. Therefore, at the plasma concentrations of laudanosine found in humans after administration of atracurium, laudanosine increased the MAC of halothane in rabbits. PMID- 2932983 TI - Detection of picogram levels of sufentanil by capillary gas chromatography. AB - Sufentanil and its two primary metabolites, N-(4-[methoxymethyl]-4-piperidinyl)-N phenyl propanamide (MPPP), and N-(4[hydroxymethyl]-1-[2-thienylethyl]-4 piperidinyl)-N-phenyl propanamide (desmethyl sufentanil), were detected by capillary gas chromatography with a nitrogen-phosphorous detector. The detection limit for sufentanil and its metabolites is 30-50 pg/ml with minimal interfering substances in the chromatograms. This method allowed for the detection of serum sufentanil in the terminal elimination phase of sufentanil in a patient receiving 1.5 micrograms/kg and will allow for studies to determine the pharmacokinetics and metabolism of sufentanil in a wide variety of patient groups now receiving this agent. PMID- 2932984 TI - Postoperative respiratory depression and elevated sufentanil levels in a patient with chronic renal failure. PMID- 2932985 TI - Acute respiratory arrest and rigidity after anesthesia with sufentanil: a case report. PMID- 2932986 TI - Problems in interpreting gastric pressure measurements. PMID- 2932987 TI - Therapy of atherosclerotic arteriopathy of lower limbs. Aspects and results. AB - As far as therapy is concerned, atherosclerotic arteriopathy may be divided into acute and chronic forms. In acute embolic forms, therapy should be surgical. Only in cases of peripheral embolism or polyembolism, and in rare cases for which vascular surgery cannot be adopted, can thrombolysis be carried out with UK. In acute thrombotic forms, therapy should be medical, because a thrombus of recent formation is rich in fibrin and may be lyzed by UK. Total recanalization takes place in 61% of cases treated, partial recanalization in 23%. Subsequently perviousness is maintained by adequate antithrombotic therapy. In chronic arteriopathy, the thrombus is lacking or almost lacking in fibrin and thrombolytic therapy is not indicated. Special therapeutic combinations are used containing platelet inhibitors (ticlopidine), antifibrin drugs (subcutaneous heparin), minor fibrinolytic agents (mesoglycan) and hemorheological drugs (pentoxyphylline). This therapy seems to give good results, as showed by the low percentage in amputation calculated on 2,565 patients treated and kept under observation for 5 years. Finally let us consider chronic progressive arteriopathy. This term indicates a very advanced stage, characterized by a gradual irreversible change for the worse leading towards gangrene. As a last resort, before amputating, a thrombolytic therapy with UK was tried to see if with strong fibrinolysis continued for 3 days amputation might be avoided. In a pilot study carried out on 12 patients, the angiographic data showed only partial lysis in small arteries or arterial branches. Clinical data showed reduction or disappearance of pain at rest in 80% of cases. In 70% of cases gangrene disappeared if it was initial and superficial, it was delimited if already in progress. PMID- 2932988 TI - Economic impact of transluminal angioplasty. AB - Using actual bills and follow-up records we attempted to determine the economic impact of percutaneous transluminal angioplasty. The patients selected included forty angioplasties performed early in our experience as well as forty comparable patients who had operations in the same period of time. Clinical follow-up was obtained over four years. The statistics obtained demonstrate the hospital bills for angioplasty were only 24% that of surgical treatment for femoral lesions ($1,329.00 versus $6,112.00) and 16% for iliac lesions ($1,353.00 versus $7,732.00). Using this patient sample and readily available statistical data, we calculated direct national savings for using angioplasty on all patients suitable and used a standard value of life analysis to estimate the value of lives saved by doing the less dangerous procedure. The sum total savings in the United States from using angioplasty in all suitable candidates as opposed to surgery would be $180 million per year for femoral lesions and $117 million for iliac lesions. This could produce a significant savings in medical costs over the coming years. PMID- 2932990 TI - Respiratory muscle activity and thoracoabdominal motion during acute episodes of asthma during sleep. AB - To understand the mechanisms of respiratory system compensation to internal loading during sleep, all-night sleep studies were performed in 10 patients with chronic stable asthma. We used noninvasive measurements to identify the onset of increased airway resistance in sleep. In each sleep study, we recorded arterial oxygen saturation (SaO2) and an array of electromyograms (diaphragm, external intercostal and sternomastoid) as well as thoracoabdominal motion. Only 4 patients developed acute asthma during sleep. A total of 6 such attacks were recorded. The attacks were detected by audible wheeze, augmentation of diaphragm, external intercostal and sternomastoid activity, associated with distinctive changes in thoracoabdominal motion. The duration of these acute asthmatic attacks ranged between 20 and 140 min. One attack started in stage I/II non-rapid-eye movement (NREM) sleep, 3 in stage III/IV NREM sleep, and 2 in rapid-eye-movement (REM) sleep. Acute asthma in NREM sleep resulted in a paradoxical inward displacement of the abdomen during early inspiration. Attacks occurring during REM sleep resulted in rib cage inward displacement during inspiration. Attacks occurring during REM sleep resulted in rib cage inward displacement during inspiration. Attacks occurring in both NREM and REM sleep did not result in a significant fall in SaO2. We conclude that acute internal respiratory loading during sleep can provoke different compensatory mechanisms in order to provide adequate ventilation in adult asthmatics. PMID- 2932991 TI - A comparison of external velour and double velour Dacron grafts in the canine thoracic aorta. AB - Six external velour (Bionit C. R. Bard, Inc.; Billerica, MA) and 11 double velour (Microvel Meadox Medicals, Inc.; Oakland, NJ) warp-knit Dacron grafts with lengths of 6 cm and diameters of 8 mm were implanted in the canine upper descending thoracic aorta for 56 days. Differences were observed: four of 11 double velour grafts developed major perigraft hematomas, while none of the external velour grafts exhibited this complication. Healing of the external velour grafts was virtually complete (average full wall healing and endothelial like cell coverage of 97.0%, SD 5.9%) in contrast to the seven (of 11) double velour grafts that were free of perigraft hematoma (average full wall healing and endothelial-like cell coverage of 40.9%, SD 20.9%). PMID- 2932989 TI - Influence of albuterol, cromolyn sodium and ipratropium bromide on the airway and circulating mediator responses to allergen bronchial provocation in asthma. AB - The effect of pharmacologic agents on mast cell mediator release was investigated in vivo. Eight atopic asthmatic subjects with airways relatively unreactive to nonspecific stimuli (geometric mean PC20 methacholine, 4.0 mg/ml) underwent single-concentration allergen challenge before (control) or after inhaling albuterol 200 micrograms, cromolyn sodium 20 mg, or 0.9% sodium chloride placebo. Six of the same subjects also underwent allergen challenge after pretreatment with ipratropium bromide, 1 mg. Airway responses to pharmacologic agents and bronchial challenge were measured by change in both specific airway conductance (SGaw) and FEV1. Mast cell mediator release was monitored by serial change in plasma histamine and, in addition, serum neutrophil chemotactic factor (NCF) on the placebo, albuterol, and cromolyn sodium challenge days. Control and placebo allergen challenges were associated with repeatable mean maximal falls in SGaw (48.5 versus 49.6%) and FEV1 (25.7 versus 25.5%). The mean increments in plasma histamine were not significantly different on the control (0.17 to 0.44 ng/ml) or placebo challenge days (0.18 to 0.64 ng/ml), with maximal levels occurring 5 min after challenge. A sustained increase in NCF was identified on the placebo challenge day (155.0% above baseline). Pretreatment with albuterol abolished any significant bronchoconstriction, with mean maximal falls in SGaw and FEV1 after challenge of 7.5 and 1.4%, respectively. These changes in airway caliber were not associated with any significant increment in mean plasma histamine (0.17 to 0.22 ng/ml) or serum NCF (4.1% increase). Cromolyn sodium pretreatment, while attenuating the airway response, was still associated with significant falls in SGaw (22.7%) and FEV1 (7.3%) and increases in plasma histamine (0.18 to 0.27 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2932992 TI - [Evan's syndrome and immunologic pancytopenias]. PMID- 2932993 TI - [The dysplastic nevus syndrome]. PMID- 2932994 TI - A new type of balloon catheter for intraoperative angioplasty. PMID- 2932995 TI - [Infarction of the right ventricle. Contribution of two-dimensional echocardiography]. AB - This study, based on 39 cases, confirms the value of two-dimensional echocardiography in the diagnosis of right ventricular infarction during the acute phase. This diagnosis is confirmed by the presence of abnormalities of the segmental kinetics always present in the inferior wall and less frequently in the anterior wall. The inferior part of the septum is affected in two thirds of cases. Right ventricular dilation is frequently observed, but is not constant. Two-dimensional echocardiography has a diagnostic sensitivity similar to that of isotope ventriculography, but greater than that of haemodynamic investigations. Finally, apart from the easy demonstration of complications (tricuspid incompetence, septal rupture, intracardiac thrombosis), two dimensional echocardiography can be used to evaluate right ventricular function. PMID- 2932996 TI - The DNA translocating vertex of dsDNA bacteriophage. PMID- 2932998 TI - Breast reconstruction. Use of autogenous tissue. PMID- 2932997 TI - In vitro effect of acyclovir and other antiherpetic compounds on the replication of channel catfish virus. AB - The antiviral effect of acyclovir (ACV; 9-(2-hydroxyethoxymethyl)guanine) on the replication of channel catfish virus (CCV), a poikilothermic herpesvirus, in brown bullhead cells (BB) was studied in vitro. Acyclovir at concentrations of 2 microM and 10 microM produced a 95 to 99% reduction in plaque numbers, respectively. At 10 microM ACV did not affect the growth of uninfected BB cells which could even be subcultured for four passages in the presence of the inhibitor. To be effective ACV had to be added early in the infectious cycle and was progressively less effective when added at later times after infection. Similar to homeothermic herpesviruses, the inhibition could be reversed with the addition of excess thymidine. The effects of three other antiviral agents, adenine-beta-D-arabinofuranoside (ara-A), phosphonoacetic acid (PAA), and phosphonoformic acid (PFA) on CCV replication were evaluated either individually or in combination with ACV. Although the other agents were found to be less effective in inhibiting CCV replication than ACV, none of the agents interacted synergistically with ACV. The results indicated that interactions with ACV with ara-A, PFA and PAA were primarily additive. Mutants of CCV resistant to ACV were obtained and were found to be somewhat more resistant to PFA than was the stock CCV. PMID- 2932999 TI - Evidence for the involvement of dithiol groups in mitochondrial calcium transport: studies with cadmium. AB - The effect of cadmium on some functions of mitochondria isolated from kidneys of rat was studied. Addition of cadmium chloride to mitochondria induced stimulation of both State 4 respiratory rate and ATPase activity, which are prevented by the addition of ruthenium red. We also show that cadmium inhibits competitively calcium translocation; this inhibitory effect of cadmium is reverted by the addition of dithiothreitol. From these results, it is proposed that, similarly to Ca2+, cadmium penetrates mitochondria and binds to a membrane dithiol group, which is essential for the translocation of the cation. PMID- 2933000 TI - [Phase II study of 5'-DFUR in gastrointestinal and breast cancer]. AB - Clinical effects of daily oral administration of 5'-DFUR were studied in patients with advanced or recurrent gastrointestinal cancer and breast cancer. Cases included 5 gastric cancer, 18 colorectal cancer, 27 breast cancer and 1 malignant melanoma. Out of 38 cases who completed the treatment, CR was observed in 2 and PR in 7, the response rate being 23.7%. Out of 23 cases with breast cancer who completed the treatment, CR was observed in 2 and PR in 6, the response rate being 34.8%. Safety was evaluated in 42 cases and diarrhea was found in 17.1% of cases; however, it was easily reduced by decreasing the dosage or discontinuing administration of the drug. PMID- 2933001 TI - [Phase II study of 5'-DFUR (5'-deoxy-5-fluorouridine) by the Cooperative Study Group]. AB - Phase II study of 5'-DFUR was conducted in 195 patients with malignant tumors by the Osaka Chemotherapy Cooperative Study Group. Five CR and 20 PR cases were obtained out 133 evaluable cases and the total response rate was 18.8% (15.8% in gastric, 38.1% in breast) One PR was observed for each of head & neck and esophageal cancer. It was noteworthy that four CR were observed in breast cancer. Adverse reaction was observed in 61 out of 151 cases (40.4%), and major side effects were digestive symptoms such as diarrhea (22.5%), nausea-vomiting (11.9%) and anorexia (10.6%). These results suggest that 5'-DFUR can be useful for the treatment of malignant tumors. PMID- 2933002 TI - [A case of remission of metastatic gastric cancer lesions in the chest and abdominal wall by 5'-DFUR administration]. AB - 52-year-old female was weakened and bed-ridden by metastasis of gastric cancer to the chest and abdominal wall, and peritonitis carcinomatosa 2 years after gastrectomy. One week after administration of 5'-DFUR, 1200 mg/d, p.o., a clinical effect was seen. In 3 weeks metastatic lesions had diminished in size, ascites had decreased and the patient had regained her appetite and put on weight. She recovered sufficiently to be able to do some daily work. Pathological degeneration and necrosis of cancer cells were observed. Although she died 8 months after remission, 5'-DFUR was effective in improving her condition and prolonging her life. PMID- 2933003 TI - Reaction to topical fluorouracil of secondary lymphedema. PMID- 2933004 TI - Disabilities in survivors of low birthweight. AB - A study of those survivors weighing 2000 g or less at birth born to residents of the South East Thames Regional Health Authority in 1970, '71, and '73 was carried out by abstracting data from health visitors' and school health records. Some postnatal information was available for 78% of the children. Prevalences of reported impairments in relation to birthweight were 20% in babies of 1500 g or less, 13% in the group weighing 1501 to 1750 g, and 11% for those of 1751 to 2000 g. Only half the impairments in the first group were likely to be seriously disabling, and only a fifth were of obvious prenatal origin. In the heaviest group, about 3% were likely to become severely disabled, but in over two fifths with impairment, this was likely to be of prenatal origin and therefore more difficult to prevent. This factor together with the larger number of survivors of birthweight 1751 to 2000 g than of 1500 g or less, indicate that an increase in impairments may be seen in the heavier group if their mortality continues to fall. PMID- 2933006 TI - Obtaining parental consent--opting in or opting out? AB - In a population based project aimed at identifying children with specified disabilities within a health region, there was, rightly, concern about the transfer of data on named children across health district boundaries. Two methods of obtaining parental consent for this process were tested. High recruitment rates were achieved using an 'opting out' approach. PMID- 2933005 TI - Prevalence and disabilities in 4 to 8 year olds with cerebral palsy. AB - A register of children born between 1970 and 1979 in the South East Thames Regional Health Authority, and diagnosed as having pre-, peri-, and postnatal cerebral palsy, was set up between 1978 and 1981. We report the 527 children born between 1970 and 1974 for whom ascertainment is virtually complete. The estimated prevalence was 2.2 per 1000, with 7.4% multiple births, and 58% boys. Birthweight distribution is as expected, with 35% weighing less than 2500 g at birth. Parental permission for release of detailed medical information was sought, and the clinicians responsible gave us data on the type of cerebral palsy; details of impairments, disabilities, and anticipated future prospects; and an opinion on the probable timing of the cause. There was a high incidence of orthopaedic defects which must represent a considerable use of resources, although the prevalence of hearing and vision defects suggested that some of these may be undetected. PMID- 2933007 TI - [Intolerance to the suspension material in urethrocervicopexy under endoscopic control]. PMID- 2933008 TI - Inhibition of testicular androgen biosynthesis by chronic administration of a potent LHRH agonist in adult men. AB - The antireproductive properties of LHRH and its agonists have now been clearly established. Using various dosing regimens and routes of administration in animal experiments and in clinical trials, these peptides invariably produce paradoxical inhibitory effects on reproductive function. This ability led to the concept that gonadal steroid-dependent (responsive) tumors might also be affected in a manner analogous to that produced by gonadectomy or by antiandrogenic or antiestrogenic drugs. Numerous data have now appeared in the medical literature on the potential efficacy of the LHRH agonists as a tumor therapy. Using different agonists (D Ser6, D-Leu6 and D-Trp6-LHRH) and various dosages, the investigators were successful in inducing a "medical castration" with androgen levels comparable to castrate control subjects. Objective tumor regression and significant clinical improvement paralleled the hormonal suppression shown in our studies and by other groups. Another interesting potential clinical application of the ability of LHRH agonist to inhibit testicular function is its development as a male contraceptive. This approach is being tested by a few groups. In order to preserve potency, exogenous androgens must be administered with the agonist. Long term pituitary suppression in boys with idiopathic precocious puberty has now been achieved and premature sexual development suppressed. In man the main mechanism responsible for testicular inhibition seems to be the achievement of a temporary and reversible state of hypogonadotropic hypogonadism. Recent data show that LHRH agonist alters the ratio of bioactive and immunoreactive LH and suggest a direct effect on LH biosynthesis as a mechanism of action of LHRH agonist analogs. Other findings support the lack of direct effect of LHRH agonist on Leydig cells in humans. In view of the main potential clinical applications--as therapy for chronic hormone-dependent disease or as a male contraception--major new developments are being undertaken in the way of administration of these substances by slow delivery systems. PMID- 2933009 TI - A comparison of cardiovascular and smooth muscle effects of 5-hydroxytryptamine and 5-carboxamidotryptamine, a selective agonist of 5-HT1 receptors. AB - The pharmacological effects of 5-hydroxytryptamine (5-HT) on heart rate, arterial blood pressure and urinary bladder pressure in the rat, and on the bronchi and ileum of the guinea-pig were compared with those of 5-carboxamidotryptamine (5 CT), a compound which binds specifically and with high affinity to 5-HT1 binding sites in rat brain membranes. 5-HT caused a transient bradycardia and a triphasic blood pressure response consisting of an initial short-lasting hypotensive, a pressor and, finally, a longer-lasting depressor phase. Analysis with mecamylamine, cyproheptadine and ketanserin indicated that the initial bradycardia and hypotension, and the pressor and tachycardic responses to 5-HT were due to, respectively, the M and 5-HT2 receptors. 5-CT showed no or little activity on these receptors, but elicited a marked hypotensive response. The prolonged hypotensive effects of both 5-HT and 5-CT were apparently mediated by 5 HT1 receptors, since they were unaffected by cyproheptadine or ketanserin, but were antagonized by high doses (greater than 2.5 mg.kg-1) of methysergide, which has an appreciable affinity for 5-HT1 binding sites. On the guinea-pig bronchi and the rat urinary bladder, which were contracted by 5-HT via 5-HT2- and, in the case of bladder, also via M-type 5-HT receptors; 5-CT was without any effect. The guinea-pig isolated ileum was relaxed by low concentration (5 X 10(-6) M), probably via 5-HT1 receptors demonstrated in this tissue, and contracted by higher concentrations of 5-CT. However, the contractile effect of 5-HT on the ileum, exerted via the M- and 5-HT2-type 5-HT receptors, was much more than that of 5-CT. Our results demonstrate that 5-CT not only has a binding, but also a functional specificity for 5-HT1 receptors. This compound seems to be a useful tool for investigating 5-HT1 receptor mediated functional responses. PMID- 2933010 TI - Chemical properties of the placental FC gamma receptor. AB - The carbohydrate and amino acid compositions of the purified Fc receptor from human placental trophoblasts are described. The placental receptor is a glycoprotein. The total content of carbohydrates in the receptor is 30% (w/w). The major carbohydrate components are galactose, N-acetylglucosamine, fucose, and mannose. The placental receptor has a high content of acidic amino acids and a relatively low number of aromatic and hydrophobic amino acid residues. The ratio of contents of hydrophilic to hydrophobic amino acids is 2:1. The hydrophilic nature of the receptor molecules is shown by charge-shift electrophoresis. PMID- 2933011 TI - Graft-to--superior mesenteric vein anastomosis for mesocaval shunts. PMID- 2933012 TI - [Regulation of human autologous mixed lymphocyte reactions by monoclonal antibodies directed at T cell differentiation antigens]. PMID- 2933013 TI - [The heart and essential hypertension]. PMID- 2933017 TI - Purification and kinetic properties of phosphofructokinase from dental pulps of rat incisors. AB - Phosphofructokinase (EC 2.7.1.11) was partially purified 19-fold from dental pulps of rat incisors, by ammonium-sulphate fractionation and phenyl-Sepharose chromatography with a recovery of about 95 per cent. With a 0.05 M tris-HCl buffer, the pH optimum of the enzyme was determined to be 8.4. At this pH, substrate inhibition of the enzyme by either fructose-6-phosphate (F6P) or ATP was not observed, and the relationship between reaction velocity and each substrate concentration was well explained by the Michaelis-Menten equation. The Km values were determined to be 5 X 10(-5) and 1.8 X 10(-4) M for ATP and F6P, respectively. The enzyme, however, showed different catalytic properties at pH 7.6, i.e. the kinetic behaviour was sigmoidal with respect to F6P and it was inhibited by high concentrations of ATP. The Hill coefficient for F6P was determined graphically to be 1.4. At pH 7.6, the enzyme activity was inhibited by citrate and phosphoenolpyruvate (PEP), neither of which showed any inhibitory effect on the enzyme at pH 8.4. PMID- 2933018 TI - Hyaluronidase and retinal function. AB - Using the incubated isolated rat retina, the effects of hyaluronidase on the electroretinogram (ERG) and metabolic activities were investigated. Initial experiments established the activity of hyaluronidase needed to liquefy, within 15 to 30 minutes, the vitreous of postmortem human eyes; this concentration was 1,000 units/mL. Rat retinas were superfused with a bicarbonate-buffered, oxygenated medium to which hyaluronidase was added in activities ranging from 100 to 5,000 units/mL. These concentrations of hyaluronidase did not significantly alter the amplitudes of the a waves and b waves of the ERG in comparison to their control amplitudes. Measurements were also made of lactic acid production, oxygen consumption, glutathione content, and adenosine triphosphatase activities in control and hyaluronidase-exposed retinas. In the presence of hyaluronidase, their respective values were similar to the controls for all biochemical factors studied. The present experiments demonstrate that addition of hyaluronidase to an "ocular irrigating" solution results in normal ERGs and normal retinal metabolic activity and suggests the possibility that hyaluronidase may be useful in enzyme assisted vitrectomy. PMID- 2933014 TI - Cerebral blood flow and cognitive testing correlate in Huntington's disease. AB - Brain atrophy estimated by computed tomographic (CT) scanning and mean hemispheric and regional gray matter cerebral blood flow (CBF) values were measured in patients with mild to moderate Huntington's disease (HD) (N = 16) using the xenon Xe 133 inhalation method and in asymptomatic blood relatives at risk from HD (N = 6) using both the xenon Xe 133 inhalation and the stable xenon CT contrast CBF methods. Results were compared with measurements in two groups of age-matched normal volunteers (N = 48 and N = 42, respectively). Significant brain atrophy in the vicinity of both caudate nuclei was present in patients with HD but not in at-risk individuals. Mean hemispheric xenon Xe 133 CBF values were reduced in patients with HD but seemed to be normal in at-risk individuals. In HD, reductions in CBF were found in both frontotemporal regions. Correlations were found between severity of dementia estimated by reductions of Mini-Mental Status Questionnaire scores and reductions of either mean hemispheric or regional frontotemporal CBF values in HD. The CT estimates of brain atrophy and three dimensional CBF by stable xenon-contrast measurements were normal in asymptomatic individuals at risk from HD. PMID- 2933016 TI - Salivary-IgA antibody to glucosyltransferase of oral microbial origin in children. AB - Salivary IgA levels were measured in whole saliva of 143 children, 2-48 months of age. The median salivary IgA concentration of children less than 12 months old was 30 micrograms/ml. A significant increase in salivary IgA concentration occurred in children 12 to 17 months old. More than 50 per cent of the population, 36 months of age and older, had Streptococcus mutans (88 per cent biotype I) recoverable from their teeth. Salivary IgA antibody levels were measured by an enzyme-linked immunosorbent assay to glucosyltransferase (GTF) antigen complexes from oral streptococci. Salivary IgA antibody to GTF from Streptococcus sanguis was detected in many children. Over 40 per cent of the 43 48-month-old group had detectable salivary antibody to Strep. sanguis GTF; salivary IgA antibody to Strep. mutans GTF (biotype I) was less frequently detected. Most subjects with salivary antibody to Strep. mutans GTF had antibody to Strep. sanguis GTF but only 23 per cent with salivary antibody to Strep. sanguis GTF had antibody to Strep. mutans GTF. Antibody to Strep. sanguis GTF was infrequently associated with the recovery of Strep. mutans from the teeth. PMID- 2933019 TI - A practical guide for the prevention of catheter-associated urinary tract infections. PMID- 2933020 TI - Counseling in urology. PMID- 2933021 TI - End-stage renal disease and renal transplantation. PMID- 2933015 TI - Hexosaminidase-A deficiency presenting as atypical juvenile-onset spinal muscular atrophy. AB - Three patients from two families had an unusual phenotypical variant of late onset hexosaminidase-A deficiency. The clinical picture was dominated by spinal motor neuron involvement mimicking juvenile-onset spinal muscular atrophy. Atypical features included prominent muscle cramps, postural and action tremor, recurrent psychosis, incoordination, corticospinal and corticobulbar involvement, and dysarthria. The presence of these atypical features in patients whose lower motor neuron involvement would otherwise be consistent with juvenile-onset spinal muscular atrophy should raise the suspicion of the presence of hexosaminidase-A deficiency and GM2 gangliosidosis that can be proved by appropriate enzyme assays. PMID- 2933022 TI - Dental treatment and radiation therapy. PMID- 2933023 TI - An inhibitor of plasminogen activator produced by tumour cell fusion hybrids. AB - Expression of plasminogen activator (PA) activity may be an important factor in the ability of tumour cells to metastasize; however, not all metastatic cells produce detectable PA activity. Conditioned culture media from revertant metastatic clones of cells derived by fusion of metastatic and non-metastatic rat mammary adenocarcinoma cells were found to contain a potent inhibitor of PA. This inhibited thrombin, human urokinase (UK) and tumour-derived PA, but not plasmin or trypsin. Inhibition was still obtained after polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate (SDS-PAGE) of mixtures of PA and inhibitor, followed by development of PA activity on fibrin overlays. The PA inhibitor eluted from Sephadex G-200 over a broad M.wt. range (35,000 80,000) and was inactivated by heating to 70 degrees for 30 min. The appearance of inhibitory activity in the culture media was time-dependent and could be reduced by incubation of cells with cycloheximide. Because of these findings, the possible presence of inhibitors should be considered in investigations into the role of PA in the metastatic process. PMID- 2933025 TI - Percutaneous transluminal angioplasty: experience at Westmead Centre. PMID- 2933024 TI - The treatment of hirsutism: experience with cyproterone acetate and spironolactone. PMID- 2933026 TI - The effects of dehydroepiandrosterone on the rate of development of cancer and autoimmune processes in laboratory rodents. PMID- 2933027 TI - Hypersensitivity to DNA-damaging agents in abiotrophies: a new explanation for degeneration of neurons, photoreceptors, and muscle in Alzheimer, Parkinson and Huntington diseases, retinitis pigmentosa, and Duchenne muscular dystrophy. PMID- 2933028 TI - Ribitol dehydrogenase of Klebsiella aerogenes. Sequence of the structural gene. AB - The ribitol dehydrogenase gene was cloned from wild-type Klebsiella aerogenes and also from a transducing phage lambda prbt which expresses the rbt operon constitutively. The coding sequence for 249 amino acids is separated from the following D-ribulokinase gene by 31 base pairs containing three stop codons, one of which overlaps the ribosome binding site for D-ribulokinase. Three residues in the amino acid sequence differ from that predicted from the DNA sequence: Asp-212 for Asn-212 is probably a protein sequencing error, but -Ala-Val- for -Ser-Ser- at 146-147 appears to be a 'neutral mutation' that may have arisen during prolonged chemostat selection of a strain that superproduces the enzyme from which the protein sequence was determined. PMID- 2933029 TI - Molecular distinctions between heparan sulphate and heparin. Analysis of sulphation patterns indicates that heparan sulphate and heparin are separate families of N-sulphated polysaccharides. AB - Heparan sulphate and heparin are chemically related alpha beta-linked glycosaminoglycans composed of alternating sequences of glucosamine and uronic acid. The amino sugars may be N-acetylated or N-sulphated, and the latter substituent is unique to these two polysaccharides. Although there is general agreement that heparan sulphate is usually less sulphated than heparin, reproducible differences in their molecular structure have been difficult to identify. We suggest that this is because most of the analytical data have been obtained with degraded materials that are not necessarily representative of complete polysaccharide chains. In the present study intact heparan sulphates, labelled biosynthetically with [3H]glucosamine and Na2(35)SO4, were isolated from the surface membranes of several types of cells in culture. The polysaccharide structure was analysed by complete HNO2 hydrolysis followed by fractionation of the products by gel filtration and high-voltage electrophoresis. Results showed that in all heparan sulphates there were approximately equal numbers of N-sulpho and N-acetyl substituents, arranged in a similar, predominantly segregated, manner along the polysaccharide chain. O-Sulphate groups were in close proximity to the N-sulphate groups but, unlike the latter, the number of O-sulphate groups could vary considerably in heparan sulphates of different cellular origins ranging from 20 to 75 O-sulphate groups per 100 disaccharide units. Inspection of the published data on heparin showed that the N-sulphate frequency was very high (greater than 80% of the glucosamine residues are N-sulphated) and the concentration of O-sulphate groups exceeded that of the N-sulphate groups. We conclude from these and other observations that heparan sulphate and heparin are separate families of N-sulphated glycosaminoglycans. PMID- 2933030 TI - Mechanism of action of rabbit liver phosphoglucomutase. AB - Induced-transport tests with comparatively undegraded rabbit liver phosphoglucomutase show that the enzyme possesses a phosphoenzyme mechanism and that any interconversion of phosphoenzyme forms is very rapid. A relatively stable 32P-labelled phosphoenzyme was isolated, which exchanged label rapidly with substrates. The phospho group appears to be bonded to a serine residue on the enzyme. PMID- 2933031 TI - The sequence of two peptides isolated from the Ca2+-transporting ATPase of rabbit sarcoplasmic reticulum after cleavage at tryptophan. AB - Cleavage of reduced, carboxymethylated, delipidated CA2+-transporting ATPase protein from rabbit sarcoplasmic reticulum with dimethyl sulphoxide/HBr yielded two long peptides (38 and 73 residues), distinct from the known major sequences of the ATPase. The longer peptide contained at least two cysteine residues, which were disulphide-linked in the native protein. It was therefore derived from the B fragment of the ATPase in which the disulphides had previously been located. It probably formed a loop on the luminal side of the membrane, spanning two membrane buried tryptophan residues. The N-terminal sequence of this peptide, (Trp)-Phe Met-Tyr-Ala, forms the basis for an oligodeoxynucleotide probe, the use of which to identify cDNA corresponding to the ATPase is described elsewhere [MacLennan, Brandl, Korczak & Green (1985) Nature (London) 316, 696-700]. PMID- 2933032 TI - Rat atrial natriuretic polypeptide stimulation of adrenal zona glomerulosa cell growth. AB - Rat atrial natriuretic polypeptide (rANP) was found to stimulate [3H] thymidine incorporation into the DNA of bovine adrenal glomerulosa cells in a primary culture in a dose-dependent manner. The minimum effective dose was a very low concentration (10(-12) M of ANP), suggesting that ANP had a physiological effect. These findings are the first indication that ANP possesses growth-stimulating activity with regard to adrenal zona glomerulosa cells. PMID- 2933033 TI - Cobalt-(cysteinyl)4 tetrahedra in yeast cobalt(II)-thionein. AB - The conversion of yeast Cu(I)-thionein into the Co(II) derivative was successful. 2.6 Co atoms were incorporated per mole of protein yielding a Co : S ratio of 1 : 3. The electronic absorption of this highly air sensitive Co(II)-thionein is virtually identical to those of the Co(II) derivatives of other metallothioneins originating from vertebrates and N. crassa. Weaker Cotton extrema are noticed and the two doublet splittings of Cu-thionein disappeared. Throughout the molar ellipticities of the cobalt protein were markedly lower compared to those of the Cu-thionein. Owing to the characteristic charge transfer bands and d-d transitions a tetrahedral Co-thiolate coordination was deduced. The best fit proposal maintaining the above Co : S ratio of 1 : 3 was a six-membered ring with three bridging cysteine sulphurs. PMID- 2933035 TI - Sodium ion stimulates the release of atrial natriuretic polypeptides (ANP) from rat atria. AB - The release of atrial natriuretic polypeptides from spontaneously beating isolated rat atria was found to be sensitive to the increase in the concentration of sodium ion. The osmotic pressure, when produced by pharmacologically inactive choline chloride, also increased the release of ANP but substantially less than the sodium ion. Sodium ion and osmotic pressure stimulated the release of ANP in the hyperosmotic but not in the hypo-osmotic range. Neither stretch nor several neurotransmitters tested had any effects on the rate of ANP secretion. PMID- 2933034 TI - Filamin inhibits actomyosin ATPase activity in platelet. AB - Filamin, an actin cross-linker protein, has been shown to exist in platelet. The role of this protein in the platelet has remained unclear. In this report, we show that filamin inhibits the actin-activated Mg2+ -ATPase activity of platelet myosin. The activation caused by platelet actin is inhibited by 50% at the molar ratio of filamin to actin of 1/50. Platelet tropomyosin, which we showed to enhance the ATPase activity, does not abolish the effect of filamin. The results support the view that filamin stabilizes the actin network in the resting platelet. PMID- 2933036 TI - Comparison of synexin isotypes in secretory and non-secretory tissues. AB - Three synexin isotypes were identified in bovine liver or adrenal medullary tissues by immune blotting of one- or two-dimensional SDS gels and by two dimensional tryptic peptide mapping of gel bands or spots. These isotypes were: alpha-synexin, mass 47 kDa, pI 6.9; beta-synexin, mass 47 kDa, pI 6.5; and mu synexin, mass 51 kDa, pI 6.1. A non-secretory tissue, bovine skeletal muscle, was found to contain only mu-synexin. The absence of alpha- and beta-synexins in a non-secretory tissue suggests these proteins may perform specific roles in the process of exocytosis. PMID- 2933037 TI - Stimulation of the Ca2+-dependent polymerization of synexin by cis-unsaturated fatty acids. AB - The influence of fatty acids on the polymerization of synexin was studied by monitoring light scattered from solutions of purified synexin. Cis-unsaturated fatty acids such as arachidonate or oleate stimulated synexin polymerization at sub-micromolar concentrations, while saturated fatty acids, a trans unsaturated fatty acid or a fatty acid methyl ester had little effect. The polymerization of synexin occurred at lower concentrations of Ca2+ in the presence of the fatty acids than in the absence of fatty acids. Therefore, Ca2+ and free fatty acids may act as co-regulators of synexin action in stimulated secretory cells. PMID- 2933038 TI - Isolation of calelectrin-like proteins associated with smooth muscle plasma membranes. AB - Plasma membranes prepared from pig stomach smooth muscle (antral part) were extracted with Triton X-100 to isolate insoluble cytoskeletal components. Reextraction of the insoluble material in EGTA yielded a protein complex which resembled the family of proteins that has been designated as 'mammalian calelectrins' [Sudhof, T.C. et al. (1984) Biochemistry 23, 1103-1109]. Plasma membranes prepared in the presence and in the absence of 0.6 M KCl differed by the amount of these proteins, but in both preparations the EGTA-extractable proteins were quantitatively important constituents. Two of these proteins were further purified by means of ion exchange chromatography to apparent homogeneity as judged from sodium dodecyl sulfate gel electrophoresis. PMID- 2933039 TI - Calcium-independent bacterial activator of cyclic nucleotide phosphodiesterase and Ca2+/Mg2+-ATPase. AB - Ca2+-independent protein-modulator (BacM) was found in the culture medium of Staphylococcus aureus. BacM activated calmodulin-dependent cyclic nucleotide phosphodiesterase and Ca2+/Mg2+-ATPase in the same way as calmodulin. BacM was shown to be a proteolytic fragment of the exotoxin secreted by the S. aureus strain under study. The kinetic analyses of the ATPase activation by BacM and CaM were performed. These studies demonstrated that the enzyme molecule contains at least two activator-sensitive sites. Experiments on the ATPase activation by Ca2+ both in the presence and in the absence of BacM and CaM documented that CaM ATPase and BacM-ATPase complexes can exist at low concentrations of calcium. Analysis of activation curves of ATPase by Ca2+ revealed three Ca2+-binding sites in the enzyme-activator complex. PMID- 2933040 TI - Increased levels of myosin mRNAs in spontaneously hypertensive rat heart. AB - RNAs isolated from normal and spontaneously hypertensive (SHR) rat heart tissues were examined by direct hybridization assay using cloned DNA probes containing chicken cardiac myosin light chain and heavy chain specific cDNA sequences. In 7 weeks old SHR heart, the level of mRNA hybridizable to these probes is the same as in normal rat heart. However, at 18 weeks of age, when hypertrophy in SHR is well established as a consequence of age-related increase in blood pressure and cardiac mass, there is an increase in SHR mRNA levels consistent with the increase in the corresponding proteins. Thus, the increase in mRNAs for major myofibrillar proteins and the onset of hypertrophic state in SHR appear to occur simultaneously. PMID- 2933041 TI - Slow calcium channel blockers and calmodulin. Effect of felodipine, nifedipine, prenylamine and bepridil on cardiac sarcolemmal calcium pumping ATPase. AB - The effect of four slow Ca2+ channel blockers (felodipine, nifedipine, prenylamine and bepridil) that possess the ability to bind to calmodulin (CaM) section and to inhibit myosin light chain kinase (MLCK) on CaM-regulated Ca2+ pumping ATPase of cardiac sarcolemma (SL) and brain cyclic AMP phosphodiesterase (PDE) was studied. The ability of these drugs to inhibit Ca2+ pumping ATPase correlated with their inhibitory effect on CaM-activated Ca2+-dependent PDE. Nifedipine was unable to inhibit markedly both enzymes. Prenylamine also was a weak inhibitor, which was unexpected because of its CaM binding potency. Felodipine (10-50 microM) and bepridil (50 microM) markedly reduced activities of SL Ca2+ pumping ATPase and PDE. Striking differences were, however, demonstrated when Ca2+ and CaM concentrations, respectively, were increased. Previously it was reported that inhibition of the SL Ca2+ pumping ATPase by the CaM antagonist calmidazolium could be overcome by increasing Ca2+ concentrations (J. M. J. Lamers and J. T. Stinis, Cell Calcium 4, 281-294, 1983). Felodipine (10-50 microM) in the present study, appeared to be equipotent with calmidazolium in reducing Ca2+ pumping ATPase, but increasing Ca2+ up to 12.2 microM could not counteract this effect. Felodipine (2-10 microM) also inhibited brain PDE noncompetitively with respect to CaM contrary to the competitive effectors calmidazolium and bepridil. On the other hand, bepridil (10-20 microM) decreased or increased Ca2+ pumping ATPase activity depending on the Ca2+ concentration (0.29 and 12.2 microM, respectively) used. These findings suggest at least two types of CaM antagonists, which can be discriminated on basis of their inhibition patterns of PDE and heart SL Ca2+ pumping ATPase. PMID- 2933043 TI - Effects of 6-aminonicotinamide on cell growth, poly(ADP-ribose) synthesis and nucleotide metabolism. AB - The purpose of this study was to determine if the cytotoxic effects of 6 aminonicotinamide are solely the result of an inhibition of poly(ADP-ribose) synthesis. The effects of 6-aminonicotinamide on cell growth, poly(ADP-ribose) synthesis and nucleotide concentrations were compared with the effect of 3 aminobenzamide, a more potent inhibitor of poly(ADP-ribose) synthesis. The growth of L1210 cells was not inhibited by 1 mM 3-aminobenzamide and was only slightly inhibited by 5 mM 3-aminobenzamide even though poly(ADP-ribose) synthesis, as measured by the N-methyl N-nitrosourea induced depletion of NAD+, was inhibited substantially. In contrast, 6-aminonicotinamide was found to be a potent inhibitor of L1210 and CHO cell growth. A 5 mM concentration of 3-aminobenzamide had no effect on purine and pyrimidine ribonucleotide concentrations or on the ATP to ADP ratio, but it did cause a slight elevation of NAD+. 6 Aminonicotinamide at 0.01 mM caused a depletion of purine and pyrimidine nucleotides and NAD+ as well as a reduction in the ATP to ADP ratio. 6 Aminonicotinamide at 1 mM caused a substantial inhibition of purine nucleotide synthesis from [14C] glycine but did not stimulate ATP breakdown. We conclude that inhibition of poly(ADP-ribose) synthesis caused little growth inhibition in itself and that the effects of 6-amininicotinamide on nucleotide metabolism were sufficient to produce an inhibition of both cell growth and DNA repair. PMID- 2933042 TI - Modulation of 5-iodo-2'-deoxyuridine metabolism and cytotoxicity in human bladder cancer cells by fluoropyrimidines. AB - Iododeoxyuridine (IdUrd) potentiated the lethal but not the growth inhibitory properties of fluorouracil (FUra) and fluorodeoxyuridine (FdUrd) in human bladder cancer cells (T24). The rate of incorporation of IdUrd into DNA was enhanced by both fluoropyrimidines, but to a significantly greater extent by FdUrd. Both inhibition of iododeoxyridylate dehalogenation and the depletion of thymidine triphosphate pools contributed to the increased incorporation rate. Inhibition of dehalogenation accounted for 67% of the observed stimulation in the case of FUra, but only 37% of the increase produced by FdUrd. The depletion of dTTP pools, both in the presence and absence of IdUrd, was greater after FdUrd than FUra exposure. The observed increase in the rate of incorporation of IdUrd appears to account for the enhanced toxicity seen with FdUrd, but other factors may be involved in the case of FUra. Since FUra and IdUrd appear to be mutually potentiating and do not share a dependence on thymidine kinase activity, this drug combination warrants further investigation. PMID- 2933044 TI - Kinetics of conjugation and oxidation of nitrobenzyl alcohols by rat hepatic enzymes. AB - Previous work has suggested that quantitative differences in the in vitro and in vivo metabolism of mononitrotoluene isomers are a result of differences in the hepatic conjugation and oxidation of the first metabolic intermediates, the mononitrobenzyl alcohols. We have determined the steady-state kinetic parameters, Vmax, Km and V/K, for the metabolism of the nitrobenzyl alcohols by rat hepatic alcohol dehydrogenase, glucuronyltransferase, and sulfotransferase. 3-Nitrobenzyl alcohol was the best substrate for cytosolic alcohol dehydrogenase (Vmax = 1.48 nmoles/min/mg protein, V/K = 3.15 X 10(-3) nmoles/min/mg protein/microM, Km = 503 microM). Vmax and Km values for 4-nitrobenzyl alcohol were similar, but V/K was about 60% of that for 3-nitrobenzyl alcohol. 2-Nitrobenzyl alcohol was not metabolized by the alcohol dehydrogenase preparation used here, but it was metabolized to 2-nitrobenzoic acid by a rat liver mitochondrial preparation. 2 Nitrobenzyl alcohol was the best substrate for microsomal glucuronyltransferase (Vmax = 3.59 nmoles/min/mg protein, V/K = 11.28 X 10(-3) nmoles/min/mg protein/microM, Km = 373 microM). The Vmax for 3-nitrobenzyl alcohol was similar, but the V/K was about half and the Km was about twice that for 2-nitrobenzyl alcohol. The Vmax for 4-nitrobenzyl alcohol was about 40% and the V/K was about half that for 2-nitrobenzyl alcohol. The best substrate for cytosolic sulfotransferase was 4-nitrobenzyl alcohol (Vmax = 1.69 nmoles/min/mg protein, V/K = 37.21 X 10(-3) nmoles/min/mg protein/microM, Km = 48 microM). The Vmax values for the other two benzyl alcohols were similar, but the V/K and Km values were about 11 and 400%, respectively, of those for 4-nitrobenzyl alcohol. These data are in qualitative agreement with results obtained when the nitrobenzyl alcohols were incubated with isolated hepatocytes, but they do not allow quantitative modeling of the data from hepatocytes. PMID- 2933045 TI - Total lymphoid irradiation in patients with refractory rheumatoid arthritis. AB - Eleven patients with rheumatoid arthritis that had been refractory to conventional drug therapy were treated with total lymphoid irradiation (TLI). Followup continued for 6 months in 9 patients, 12 months in 6 patients, and 24 months in 3 patients. At 6 and 12 months post-TLI, a significant improvement in clinical disease activity was demonstrated. Side effects noted during TLI included fatigue, nausea, diarrhea, and vomiting. One patient died of cardiorespiratory arrest, 2 patients died of kidney failure secondary to generalized amyloidosis, and 1 patient died of septic shock secondary to a multilocular septic arthritis. One patient experienced 2 episodes of septic arthritis; 2 patients manifested delayed wound healing. Immunologic assessments showed consistent lymphopenia in all patients. T lymphocyte subsets decreased after TLI, and showed a transient increase at 6 months post-TLI. The suppressed mitogen responsiveness, which was noted 2 months after irradiation, was found to increase almost to the pre-TLI levels at 12 months. The observed increase in morbidity and mortality after TLI is evidence that discourages the use of this therapeutic technique, at least in its present form. PMID- 2933048 TI - Interleukin 1: an immunological perspective. PMID- 2933047 TI - [Transluminal laser angioplasty: an experimental evaluation of the potentials of recanalization using a YAG-neodymium laser]. PMID- 2933046 TI - Enteral and parenteral nutrition of low birth weight infants. PMID- 2933049 TI - Effector and regulatory mechanisms in immunity to schistosomes: a heuristic view. PMID- 2933050 TI - A comparison of the endocrine effects of low dose aminoglutethimide with and without hydrocortisone in postmenopausal breast cancer patients. AB - The endocrine effects of 125 mg (low dose) aminoglutethimide (AG) twice daily (b.d.) were compared with those of 125 mg AG + 20 mg hydrocortisone (HC) b.d. in 23 and 45 postmenopausal patients with advanced breast cancer, respectively. The patients in each group were drawn from two separate populations, but the mean age and weight of the groups were similar and there were no significant differences between the pretreatment serum levels of the hormones investigated. Serum oestrone and oestradiol levels were suppressed by both treatments, but there was a significantly greater suppression by AG + HC. This greater suppression is probably due to the observed increase in serum androstenedione (i.e. precursor) levels with AG alone, whilst with AG + HC these levels were found to be reduced. In terms of suppression of serum oestrogen levels it is of benefit to combine low dose AG with HC. PMID- 2933052 TI - Conception during 'Diane' therapy--a successful outcome. PMID- 2933051 TI - Changes in subcellular calcium transport in rat hearts during the calcium paradox. AB - Changes in the transport of calcium in the sarcoplasmic reticulum (SR) and mitochondria (MT), of the rat heart during calcium paradox were investigated. Calcium binding and uptake by SR in the paradox hearts were from about 1.5 to 2 times greater than in normal hearts, whereas in the MT of the paradox hearts they were about half those of normal hearts. There was no difference between paradox and normal hearts in calcium stimulated ATPase activity in the SR. The ultrastructure of the MT was disrupted in calcium paradox, but the SR was essentially the same as in normal hearts. We propose that during calcium paradox, the intracellular calcium overload damages both calcium transport and the ultrastructure of the MT, but that calcium transport by the SR is accelerated to compensate for the calcium overload. PMID- 2933054 TI - Treatment of chondrodermatitis nodularis helicis and conventional wisdom? PMID- 2933053 TI - Vitamin A in skin and serum--studies of acne vulgaris, atopic dermatitis, ichthyosis vulgaris and lichen planus. AB - The concentrations of vitamin A and total carotenoids were measured in serum and skin of 61 patients with acne vulgaris, atopic dermatitis, ichthyosis vulgaris or lichen planus, and compared with those in 37 healthy subjects. The mean serum concentrations of retinol and retinol-binding protein were significantly decreased in patients with acne (P less than 0.01) and slightly increased in those with ichthyosis (P less than 0.05), but were otherwise normal. Serum carotenoid levels did not differ between patients and controls. Superficial shave biopsies from both involved and uninvolved skin were examined for the presence of retinol (vitamin A1), dehydroretinol (vitamin A2) and total carotenoids. The mean retinol concentration was increased in lichen planus lesions (P less than 0.05) and decreased in both acne skin (involved and uninvolved) and in lesions of atopic dermatitis (P less than 0.05). The mean dehydroretinol concentration was markedly increased in lesions of atopic dermatitis and lichen planus (P less than 0.01). No consistent abnormalities were found in skin of patients with ichthyosis vulgaris. The mean carotenoid concentration in the patients' skin did not differ significantly from that in the controls. The reduced retinol level in the skin of acne patients is probably explained by diminished supply of vitamin A from the blood. The abnormal ratio of retinol to dehydroretinol in lesions of lichen planus and atopic dermatitis is possibly due to changes in cutaneous vitamin A metabolism associated with epidermal hyperproliferation and inflammation. PMID- 2933055 TI - PUVA therapy prevents sensitization to mechlorethamine in patients with psoriasis. AB - Two groups of 20 patients with psoriasis were treated with mechlorethamine applied topically (group A) or with PUVA combined with mechlorethamine (group B). In group B mechlorethamine was started after six PUVA treatments. Results showed a significant decrease of the incidence of contact dermatitis in group B (30%) compared with group A (75%). Allergic dermatitis, demonstrated by a positive patch test to mechlorethamine with an histology of eczema, was observed in 55% of patients in group A and 20% in group B. The incidence of irritant dermatitis was not significantly different in the two groups. Allergic dermatitis was observed later in group B: after an average of 32.2 applications of mechlorethamine compared with 25 applications in group A. Possible mechanisms responsible for these results are reduction of epidermal Langerhans cells by PUVA therapy and induction of antigen-specific suppressor T cells. Patients living far from a specialized centre might be treated initially with PUVA therapy then with mechlorethamine alone, at home. This schedule may reduce the incidence of contact dermatitis to mechlorethamine. PMID- 2933056 TI - Degradation of factor VIII coagulant antigen by proteolytic enzymes. AB - The factors responsible for the lability of factor VIII coagulant activity (VIII:C) and factor VIII coagulant antigen (VIII:CAg) are poorly understood. In this study the VIII:C and VIII:CAg are studied after incubation with plasmin, trypsin or alpha-chymotrypsin. Both isolated human VIII:CAg and VIII:CAg associated with factor VIII-related antigen (VIII R:Ag) are evaluated. The antigenic sites of the VIII:CAg are somewhat more stable to the action of these enzymes than the functional activity, although both follow a generally parallel degradation. A biphasic decay curve is seen in the initial time points. No stabilization of the functional or antigenic reactivity is observed in the presence of the VIII R:Ag. Lower concentrations of each enzyme cause an initial rise in the factor VIII:C in the presence of VIII R:Ag, but not in the isolated VIII:CAg. Higher concentrations of alpha-chymotrypsin cause activation of VIII:C and a slight decrease in the VIII:CAg values in both preparations. These enzymes may play a modulating role in the coagulation cascade through the activation and degradation of VIII:C and VIII:CAg. PMID- 2933057 TI - Is bladder catheterization really necessary before laparoscopy? AB - A randomized prospective controlled trial compared a policy of bladder catheterization with no catheterization in patients undergoing laparoscopy. Of the 41 patients randomized to receive no catheterization, seven were actually catheterized on the judgement of the surgeon, but only one of them had greater than 50 ml of urine. Midstream urine obtained 6 days after laparoscopy was infected in 9 (21%) of the 42 patients allocated to receive catheterization and in only five (12%) of those allocated to the no-catheter group. Four of these five were actually not catheterized, giving an infection rate of 12% in the 34 patients not catheterized. The differences are statistically significant. A routine policy of catheterization for patients undergoing laparoscopy is questionable. All patients who are catheterized should be investigated for urinary tract infections after operation. PMID- 2933058 TI - Congenital lip pits and facial clefts. AB - Two families with congenital lower lip pits in association with cleft lip and palate, and isolated cleft palate are described. The presentation, mode of inheritance, aetiology, treatment and genetic significance are reviewed. PMID- 2933059 TI - Cleft lip and palate in Nigerian children and adults: a comparative study. AB - A survey of cleft lip and palate in 160 Nigerians is presented. In clefts of the lip alone, there was no sex predilection whereas cleft lip and palate cases showed a slight male preponderance. 119 (74.4%) cases presented below the age of 12 years and 41 (25.6%) cases were first seen above 12 years of age. Only a few cleft lip and palate cases survived to adulthood possibly because of malnutrition combined with the lethal effects of associated congenital abnormalities. This study confirms the view that late primary repair of clefts is less likely to produce impaired growth of the maxilla due to contraction of scar tissue commonly seen in early surgery. The importance of early primary repair is emphasised. PMID- 2933060 TI - Orthodontic hardware for oral surgeons. AB - The advantages and aims of joint management of orthognathic surgery patients are described. The uses of orthodontic appliances for inter-maxillary fixation and post-surgical stabilisation of the occlusion are illustrated. PMID- 2933061 TI - An investigation into post-operative pain after third molar surgery under local analgesia. AB - The pain experienced after third molar surgery was investigated over a 7 day post operative period in 80 patients. The results from the study suggest that post operative pain is of short duration and reaches its maximum intensity in the early post-operative period. Nearly all patients required an analgesic at some time during the 7 days. The sex of the patient and whether there is a previous history of pericoronitis are important determinants of post-operative pain. However, the magnitude of post-operative pain does not appear to be dependent upon the operator or related to the extent of surgical trauma as assessed by operating time and radiographic score. PMID- 2933062 TI - Dry socket incidence compared after a 12 year interval. AB - A survey was conducted over a 3 month period in 1983 to examine the influence of clinical factors on the incidence of dry socket (DS) after extractions of permanent teeth under local analgesia. The findings were compared with those of a similar 3 month survey in the same hospital in 1971. Age, sex and extraction site each significantly influenced the incidence of DS. The major difference from the 1971 survey was an increase in the DS incidence from 3.0% to 4.0% of extractions. This occurred mainly following multiple extractions and may indicate that patients, particularly in this group, are nowadays less tolerant of any post extraction discomfort and hence more readily return for attention. This is particularly relevant in the present study since the broad definition of DS used in both surveys embraced even the mildest presentations of disturbed socket healing. PMID- 2933063 TI - Antibiotic treatment of cervicofacial actinomycosis for patients allergic to penicillin: a clinical and in vitro study. AB - The minimum inhibitory concentrations for erythromycin, clindamycin, lincomycin, tetracycline and minocycline have been determined for 92 clinical and three culture collection isolates of Actinomyces. From a consideration of MIC values and expected serum levels from oral therapy, minocycline was the drug of choice for the treatment of actinomycosis in patients allergic to penicillin. The serum levels of six patients allergic to penicillin, treated with oral minocycline 1 g/day were monitored and found to exceed the MIC for the Actinomyces species responsible for the condition. In all six Actinomycosis cases resolution was achieved in 8-16 weeks of oral minocycline therapy with no recrudescence for 1 year. PMID- 2933065 TI - Primary amyloidosis causing macroglossia and respiratory symptoms. AB - Amyloidosis may involve the tongue, causing macroglossia. Such a case is described which resulted in airway obstruction. The subsequent management was by permanent tracheostomy. PMID- 2933066 TI - Primary intra-osseous carcinoma involving the maxilla. AB - Primary intra-osseous carcinoma, especially in the maxilla, is a rare sub-type of odontogenic carcinoma. The authors describe a recurrent case with maxillary involvement. In 1981, an intra-osseous maxillary tumour was excised from a 33 year-old male. There were two recurrences (in 1983 and 1984). Extra-osseous sites for the origin of the tumour were excluded. The histopathological appearance of the tumour was that of a primary intra-osseous carcinoma. At the age of 22 years, the patient had an osteosarcoma of the radius and at the age of 31 years, pulmonary tuberculosis. The differential diagnosis of primary intra-osseous carcinoma is discussed. PMID- 2933068 TI - Biotin deficiency and susceptibility to fatty liver and kidney syndrome in broiler chicks: reduced 6-phosphofructokinase (EC 2.7.1.11) activity but normal fructose 2,6-bisphosphate content in birds with hepatomegaly. AB - In two separate experiments, using different strains, broiler chicks were reared on either a commercial-type chick mash (control) or a fatty liver and kidney syndrome (FLKS)-inducing diet. In Expt a, chicks were killed on day 29 and in Expt b, on day 32. Body-weights and liver weights were measured, and values from those given the control ration used to construct a hepatomegaly index by employing a variant of linear discriminant analysis. Application of the index to FLKS birds revealed a statistically significant bimodal distribution of liver size. The birds with enlarged livers (high index) also possessed metabolic abnormalities in that 6-phosphofructokinase (EC 2.7.1.11; PFK-1) activity (measured at low substrate concentration) was depressed despite the presence of normal, or even slightly elevated fructose 2,6-bisphosphate concentration. This indicates the presence of an uncharacterized regulatory mechanism for PFK-1 in FLKS-susceptible birds. PMID- 2933064 TI - Amyloidosis with oral involvement. AB - Amyloidosis is a disease complex in which amyloid fibrils, formed from various serum proteins, may be deposited in a local or systemic distribution. When this deposition affects vital organs the disease usually is fatal because there is no effective treatment. This paper reports a case of amyloidosis with oral involvement and discusses recent advances concerning the properties of amyloid fibrils and the various pathogenic mechanisms responsible for their formation. PMID- 2933067 TI - Cementoblastoma: review of the literature and report of a case in a 7 year-old girl. AB - Cementoblastoma is a very rare tumour of mesenchymal odontogenic origin. It usually affects adolescents and young adults, the youngest patient ever reported being 8 years-old. It is treated by enucleation and has an excellent prognosis. We review the world literature on the subject and present a case of cementoblastoma in a 7 year-old girl. PMID- 2933069 TI - 1H NMR studies of lambda cro repressor. 1. Selective optimization of two dimensional relayed coherence transfer spectroscopy. AB - Two-dimensional relayed coherence transfer NMR spectroscopy (RELAY) has been used to corroborate side chain spin system identities in crowded regions of the 1H NMR spectrum of the lambda cro repressor protein. The mixing time in the RELAY experiments was optimized for specific preselected spin systems by using recently developed methods [Bax, A., & Drobny, G. (1985) J. Magn. Reson, 61, 306-320], which utilize the transverse relaxation time (T2) of the molecule and relevant J couplings for the defined spin system. We demonstrate that a mixing time of 26 ms gives rise to strong C alpha H-C gamma H3 RELAY cross peaks for all valine, threonine, and isoleucine residues, while RELAY cross peaks for other spin systems are weak or are not observed. This allows for rapid and unambiguous identification of the side chain resonances for valine, isoleucine, threonine, and alanine (by elimination). The use of optimized RELAY for analyzing and identifying spin systems in complex spectra is discussed. PMID- 2933070 TI - 1H NMR studies of lambda cro repressor. 2. Sequential resonance assignments of the 1H NMR spectrum. AB - The cro repressor protein from bacteriophage lambda has been studied in solution by two-dimensional nuclear magnetic resonance spectroscopy (2D NMR). Following the approach of Wuthrich and co-workers [Wuthrich, K., Wider, G., Wagner, G., & Braun, W. (1982) J. Mol. Biol. 155, 311-319], individual spin systems were identified by J-correlated spectroscopy (COSY) supplemented, where necessary, by relayed coherence transfer spectroscopy (RELAY). Nuclear Overhauser effect spectroscopy (NOESY) was used to obtain sequence-specific assignments. From the two-dimensional spectra, the peptide backbone resonances (NH and C alpha H) for 65 of the 66 amino acids were assigned, as well as most of the side chain resonances. The chemical shifts for the assigned protons are reported at 35 degrees C in 10 mM potassium phosphate, pH 6.8, and in 10 mM potassium phosphate, pH 4.6, 0.2 M KCl, and 0.1 mM EDTA. Small shifts were observed for some resonances upon addition of salt, but no major changes in the spectrum were seen, indicating that no global structural change occurs between these ionic strengths. NOE patterns characteristic of alpha-helices, beta-strands, and turns are seen in various regions of the primary sequence. From the location of these regions the secondary structure of cro in solution appears to be virtually identical with the crystal structure [Anderson, W. F., Ohlendorf, D. H., Takeda, Y., & Matthews, B. W. (1981) Nature (London) 290, 754-758]. Missing assignments include the Pro-59 resonances and the peripheral protons of the eight lysine, the three arginine, and three of the five isoleucine residues. PMID- 2933071 TI - Interaction of duramycin with artificial and natural membranes. AB - Duramycin is a polypeptide antibiotic (molecular weight 2012) obtained from culture filtrates of Streptomyces cinnamomeus forma azacoluta. In this work, we show that low concentrations of duramycin induced aggregation of lipid vesicles containing unsaturated phosphatidylethanolamine and unsaturated monogalactosyl diglyceride, and of sarcoplasmic reticulum vesicles from rabbit skeletal muscle. Furthermore, duramycin inhibited the ATP-dependent Ca2+ uptake in sarcoplasmic reticulum vesicles without affecting the hydrolysis of ATP or the permeability of Ca2+. Also, duramycin only inhibited the bacteriorhodopsin proton pump reconstituted into phospholipid vesicles containing phosphatidylethanolamine. We have isolated a duramycin-resistant strain of Bacillus subtilis and have mapped the location of duramycin resistance. In this strain, the secretion of protons and influx of calcium were resistant to duramycin, and its lipid composition was profoundly different from that of the parent strain. No phosphatidylethanolamine was detected in the resistant strain. Our findings are consistent with the idea that duramycin recognizes a particular membrane conformation determined by the presence of phosphatidylethanolamine or monogalactosyl diglyceride. PMID- 2933072 TI - The influence of cupric ions on porphyrin-induced photodynamic membrane damage in human red blood cells. AB - Photooxidation of various susceptible substrates with hematoporphyrin derivative (photofrin) as sensitizer was strongly inhibited by simultaneous addition of cupric acetate to the reaction mixture. With sulfhydryl-containing compounds, however, an increased rate of photooxidation was observed under these experimental conditions. Preincubation of photofrin and cupric acetate at equimolar concentrations for 24 h at room temperature yielded a stable photofrin Cu2+ complex. This complex did not act as photosensitizer with histidine, tryptophan, tyrosine, methionine or guanosine as substrates. With dithiothreitol, however, the photofrin-Cu2+ complex still acted as a photosensitizer, with an efficiency of about 30% as compared to free photofrin. Also in red blood cell membranes only sulfhydryl groups were photooxidized with the photofrin-Cu2+ complex as sensitizer. Illumination of intact erythrocytes in the presence of the photofrin-Cu2+ complex resulted in K+ leakage and, ultimately, photohemolysis. Pretreatment of the cells with N-ethylmaleimide and 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) inhibited this photodynamically induced K+ loss. Considering recent studies on the reactivity of distinct membrane SH-groups with various sulfhydryl reagents this suggests that a sulfhydryl group, located in the 17 kDa membrane bound fragment of band 3, is involved in photodynamic K+ leakage with the photofrin-Cu2+ complex as sensitizer. PMID- 2933073 TI - Preparation of a highly concentrated, completely monomeric, active sarcoplasmic reticulum Ca2+-ATPase. AB - Sarcoplasmic reticulum vesicles from fast skeletal muscle were partially delipidated with sodium cholate at high ionic strength and sedimented in a discontinuous sucrose gradient. Phospholipid content was reduced from 0.777 mumol/mg protein to 0.242 mumol/mg protein. As judged from gel electrophoresis and high pressure liquid gel chromatography, accessory proteins were removed during centrifugation and the Ca2+-ATPase was obtained in an almost pure form. Addition of myristoylglycerophosphocholine (1 mg/mg protein) reactivates ATPase and dinitrophenylphosphatase activity to the same degree obtained with native vesicles. Using the analytical ultracentrifuge it could be demonstrated that the reactivated Ca2+-ATPase was present exclusively in a monomeric state. These results were obtained at high and low ionic strength and up to a protein concentration of 10 mg/ml. Therefore this preparation should be very useful to investigate differences between oligomeric and monomeric Ca2+-ATPase. PMID- 2933075 TI - An endogenous inhibitor protein of synaptic plasma membrane (Ca2+ + Mg2+)-ATPase. AB - An inhibitor protein of synaptic plasma membrane (Ca2+ + Mg2+)-ATPase was purified to apparent homogeneity from rat cerebrum by a molecular weight cut followed by chromatography of cytosol proteins with molecular weights between 10 000 and 3500 on DEAE-Sephadex at pH 5.2. The inhibitor could be partially inactivated by proteinases and dithiothreitol, but was heat-stable. Gel filtration gave a molecular weight of about 6000. Like the (Ca2+ + Mg2+)-ATPase inhibitor protein isolated from erythrocytes, the inhibitor from brain contains a characteristic high proportion of glutamic acid (36%) and glycine (37%) residues. Synaptic plasma membrane Mg2+-ATPase and microsomal membrane (Ca2+ + Mg2+)-ATPase did not respond to the inhibitor. Synaptic plasma membrane and erythrocyte membrane (Ca2+ + Mg2+)-ATPases, however, were affected. Inhibitory influence on synaptic membrane (Ca2+ + Mg2+)-ATPase was reversible, since inhibition could be relieved upon removal of inhibitor from saturable sites on the membrane. The inhibitor is not a calmodulin-binding protein, since the concentration of calmodulin for half-maximal activation of the ATPase was unaffected by its presence. Mode of inhibition of the (Ca2+ + Mg2+)-ATPase by the inhibitor was non competitive. PMID- 2933074 TI - Reconstitution and photolabeling of the purified (Na+ + Mg2+)-ATPase from the plasma membrane of Acholeplasma laidlawii B with phospholipids containing a photosensitive fatty acyl group. AB - The purified membrane (Na+ + Mg2+)-ATPase of Acholeplasma laidlawii B was reconstituted into vesicles composed of phospholipids containing a photoactivatable aryl nitrene-generating fatty acyl group. The reconstitution with phospholipid resulted in an enhancement of ATPase activity and a reduction in the sensitivity of the enzyme to radiation inactivation. The incorporation of the enzyme into the lipid vesicles results in a broadening of the gel-to-liquid crystalline phase transition of the photolabeled phospholipid and the appearance of two partially resolved endotherms in the calorimetric traces. The temperatures and the total enthalpy of these overlapping transitions are higher than in the absence of incorporated enzyme. After photolysis of the lipid-reconstituted ATPase and separation of the polypeptide subunits by sodium dodecyl sulfate (SDS) gel electrophoresis, a significant labeling of the alpha-subunit of the enzyme was demonstrated. These results indicate that at least the alpha-subunit of this ATPase must penetrate into or traverse the phospholipid bilayer. PMID- 2933076 TI - The transport of cationic amino acids across the plasma membrane of mammalian cells. PMID- 2933078 TI - Isolation and partial characterization of keratan sulphate from human brain. AB - A sulphated glycoconjugate was isolated from adult human brain from a glycosaminoglycan fraction which was not precipitated with 1% cetylpyridinium chloride or ethanol below 50% concentration. It appeared heterogeneous on gel filtration, exhibiting a molecular weight range from about 7000 to over 10 000. Its main covalent structure was shown to contain sulphated, repeating disaccharide units of (beta-D-galactose-(1----4)-N-acetyl-D-glucosamine-(1--- 3)). In addition, it was susceptible to degradation by keratan sulphate endo-beta galactosidase and thus was assumed to be keratan sulphate. PMID- 2933077 TI - Catalytic properties of human Lys77-plasmin. A comparative steady-state and pre steady-state study. AB - Values of kinetic parameters for the hydrolysis of esters and p-nitroanilides of L-lysine and L-arginine catalyzed by the Lys77 form of human plasmin (EC 3.4.21.7) have been determined between pH 5.5 and 8 (I = 0.1 M) at 21 +/- 0.5 degrees C. Over the whole pH range explored, Lys77-plasmin catalysis conforms to simple Michaelis-Menten kinetics, and steady-state and pre-steady-state data may be consistently fitted to the minimum three-step mechanism: E + S in equilibrium (k+1/k-1)E X S----(k+2)E X P + P1----(k+3)E + P2 In spite of the higher specificity of lysyl derivatives for Lys77-plasmin rather than the arginyl ones, kinetic parameters also depend on the nature of the N-alpha substituent and/or of the alcoholic or p-nitroanilidic moiety of the substrate. Among the esters and anilides considered, ZLysONp shows the most favourable kinetic parameters and may be the substrate of choice of Lys77-plasmin, in that it allows the determination of the enzyme concentration as low as 2 X 10(-9) M (about 1 X 10(-3) CU/ml), at the optimum pH value (approx. 8). Between pH 5.5 and 8, the pH profiles of kcat and kcat/Km for the Lys77-plasmin-catalyzed hydrolysis of ZLysONp and ZArgONp reflect the ionization of a single group (probably His-602 involved in the active site) with pKa values ranging between 6.4 and 6.6; at variance, values of Km are pH-independent. PMID- 2933079 TI - Comparison of biosynthesis and subcellular distribution of lysozyme and lysosomal enzymes in U937 monocytes. AB - Using metabolic labelling and sucrose density fractionation we compared the synthesis of lysozyme and lysosomal enzymes in human monocytic U937 cells. In pulse-chase experiments in sucrose density gradients, the intracellular radioactively labelled lysozyme distributed similarly to cathepsin D and beta hexosaminidase. With the aid of immunochemical detection in Western blots, the steady-state distribution of lysozyme was found to be slightly different from that of beta-hexosaminidase; relatively more lysozyme was present in fractions sedimenting between lysosomes and the Golgi apparatus. The observed distribution of the lysozyme antigen with a prominent peak in the lysosomal fraction was in striking contrast to the broad distribution of the lysozyme activity. The difference was explained by a bias in the determination of the activity of lysozyme by the 'lysoplate' diffusion assay. PMID- 2933080 TI - The presence of lipocortin in human embryonic skin fibroblasts and its regulation by anti-inflammatory steroids. AB - Human embryonic skin fibroblasts in culture produce pro-inflammatory lipid mediators and all types of prostanoids. When these cells were treated with the anti-inflammatory steroid, dexamethasone, prostaglandin production was inhibited. This phenomenon required glucocorticoid receptor occupancy and mRNA and protein synthesis. The inhibitory effect was prevented by treating the cells with a monoclonal antibody, BF 26, raised against renocortin, a lipocortin-like protein formed in rat kidney medulla interstitial cells in culture. When the proteins present in the supernatants and the cell pellets derived from control and dexamethasone-treated cells were analyzed for their ability to inhibit phospholipase A2, four inhibitory peaks, at 45, 30, 15 kDa and one peak under 12 kDa, were found in the supernatants of control and dexamethasone-treated cells, whereas one single inhibitory peak at 15 kDa was found in the cell pellets. The antiphospholipase activity was much greater in dexamethasone-treated cells than in control cells. These results suggest that preformed lipocortin exists in human cells and that lipocortin is synthesized and released under glucocorticoid treatment. PMID- 2933083 TI - Peptide studies using a fast atom bombardment high field mass spectrometer and data system. 4. Disulfide-containing peptides. AB - Ten peptides containing one, two or three disulfides were examined to determine their behavior under fast atom bombardment (FAB) mass spectrometric conditions. The mass spectra for the disulfide and the reduced disulfide forms of each peptide were compared. Several factors were examined that contribute to the fast atom bombardment mass spectra of these peptides: components of the FAB matrix such as alkali cations, acids, bases and reducing agents, the intrinsic molecular properties of the intact peptide, and the effect of reducing conditions on sensitivity. The FAB mass spectra of the disulfide-containing peptides examined in this study displayed accurate molecular weight information and fragmentation which indicated the position of the disulfide in the amino acid sequence. PMID- 2933082 TI - [Development of research into the physiology and pathophysiology of the fibrinolysis system]. AB - A modern data review on the importance of fibrinolysis system is given. A considerable success has been scored during the study of molecular parameters of fibrinolysis system: the plasminogen, plasmin, its inhibitors, plasminogen activators and the mechanism of activation system have been characterized. The entrance of A, K, C, P and PP vitamins has been established to be necessary for the normal functioning of the fibrinolysis system; the dependence of the blood fibrinolytic activity upon the initial plasminogen content and concentration of its activators in blood has been revealed. The plasminogen activator depletion in tissues has been shown to be one of the reasons of some pathological states development, especially at cardiovascular diseases. The increase of fibrinolysis level by the active fibrinolytic ferment injection in blood has a medical effect at thrombosis. The ferment fibrinolysin received in the laboratory is successfully used in clinical practice. Some other activators of fibrinolytic system: tricholysine and longolytin from the culture of saprophyte fungi, plasminogen activator from the pig heart and the cells culture of the calf kidney have been received and are being studied. PMID- 2933081 TI - [Mechanism of the effect of EGTA on the affinity to calcium of Ca-transporting and Ca-binding cell systems]. AB - The activity of Ca-ATPases of erythrocyte ghosts and sarcoplasmic reticulum and the rate of ATP-dependent uptake of 45Ca by erythrocyte membrane inside-out oriented vesicles, sarcoplasmic reticulum vesicles and mitochondria were investigated. It was found that in all cases studied the addition of EGTA to the incubation mixture caused an increase in the affinity of Ca-pumps for Ca2+; their maximal activity remained thereby unaffected. A similar effect of EGTA was observed when the affinity for Ca2+ of calmodulin, troponin C and the fluorescent dye quin 2 were determined. It was assumed that the effect of EGTA on the affinity for Ca2+ of Ca-transporting and Ca-binding systems of a cell is due to a removal of admixtures of bi- and trivalent cations. PMID- 2933085 TI - Rapid and efficient sequence determination of a 4 nmol sample of adipokinetic hormone I (AKH I) using FAB tandem mass spectrometry. AB - Fast atom bombardment mass spectrometery in conjunction with tandem mass spectrometry provided the unambiguous sequence determination of the adipokinetic hormone I. The amount of sample needed is of the order less than or equal to 4 nmol, and the complete analysis is performed in less than 4 h. PMID- 2933084 TI - Structural investigations on the inner core region of lipopolysaccharides from Salmonella minnesota rough mutants. AB - The structure of the inner core region (L-glycero-D-mannoheptose/2-keto-3-deoxy-D mannooctulosonic acid region) of lipopolysaccharides from Salmonella minnesota rough mutants was investigated. Using conventional methods (neutral sugar analysis, Smith degradation and methylation analysis) combined with gas chromatography/mass spectrometry (GC/MS) of higher oligosaccharides (up to tetrasaccharide), the linkages of the core sugars of lipopolysaccharides from S. minnesota rough mutants, strains R4 (Rd2P-), R7 (Rd1P-) and R5 (RcP-) were determined as: (formula see text) with R representing H in R4, L-glycero-D mannoheptopyranosyl in R7, and D-glucopyranosyl-(1----3)-L-glycero-D mannoheptopyranosyl in R5, respectively. In addition, it is shown that heterogeneity within the neutral sugar part of these lipopolysaccharides is low. PMID- 2933086 TI - Comments on a 'Proposal for a common nomenclature for sequence ions in mass spectra of peptides'. PMID- 2933087 TI - Mass spectrometric fragmentation patterns for the syn and anti isomers of PGE2 and PGD2-methyloxime methyl esters and their analogs. AB - A systematic study of the mass spectral fragmentation of the methyl ester methyloxime-trimethylsilyl ether derivatives of D and E prostaglandins and selected omega-chain analogs is presented. Fragments from the omega-chain analogs are shifted the appropriate mass when compared with the parent PGD2 or PGE2. NMR data of the methyloxime methyl ester of PGE2 have permitted assignment of the syn and anti isomers (relative to the alpha chain) to the fast and slow eluting gas chromatographic peaks, respectively. PMID- 2933088 TI - Chemical modification of nucleic acids. Methylation of calf thymus DNA investigated by mass spectrometry and liquid chromatography. AB - Mass spectrometry provides an extremely sensitive method for the identification and quantification of modified nucleosides and hence for determining chemical modifications of nucleic acids. When mass spectrometry is used in conjunction with a new high-performance liquid chromatographic system capable of separating 15 methylated and naturally occurring nucleosides, this allows the quantification of products of in vitro DNA methylation. With synthetic (2H3)methyl-labeled methylnucleosides as internal references, the distribution of methylated products formed when calf thymus DNA was reacted with N-methyl-N-nitrosourea(MeNU) was determined. Five modified products, 1-methyldeoxyadenosine(m1dA), 3 methyldeoxycytidine(m3dC), 7-methyldeoxyguanosine(m7dG), 3-methylthymidine(m3T) and O4-methylthymidine(m4T) were detected and the relative distributions were measured. The ability of mass spectrometry/mass spectrometry (tandem mass spectrometry) to increase specificity and sensitivity in this determination is demonstrated and its application to in vivo studies is suggested. PMID- 2933089 TI - The mass spectrometric analysis of the urinary metabolites of melatonin and its deuterated analogues, confirming their identity as N-acetylserotonin and 6 hydroxymelatonin. AB - In a recent study, we showed that melatonin could be metabolized to N acetylserotonin and 6-hydroxymelatonin. To confirm this finding rats were administered three different forms of deuterated melatonin intraperitoneally. Their urines were analysed by gas chromatography/mass spectrometry and the results showed, in each case, that the appropriate deuterated (or non-deuterated) metabolite had been formed. From these data it is clear that N-acetylserotonin is a urinary metabolite of melatonin. PMID- 2933090 TI - Quantitative analysis of an N-oxide metabolite by fast atom bombardment tandem mass spectrometry. AB - An assay for the N-oxide metabolite of a benzazepine drug by fast atom bombardment ionization with tandem mass spectrometric analysis on a triple quadrupole mass spectrometer has been developed and validated for urine and plasma samples. This methodology allows analysis of this metabolite directly in crude sample extracts, without the need for extensive chromatography or sample derivatization. Quantification was accomplished with the use of a stable isotope analog of the analyte as an internal standard, using the selected reaction monitoring mode of operation. PMID- 2933091 TI - Determination of total iron in foods by isotope dilution fast atom bombardment mass spectrometry. AB - A method employing isotope dilution fast atom bombardment mass spectrometry has been developed for the quantitative determination of iron in foods. Samples were spiked with an enriched source of 54Fe, digested with concentrated HNO3/H2SO4 and the iron extracted from 6 M HCl into diethyl ether. Bracketing procedures gave precisions ranging from 1.30-4.49% relative standard deviation (RSD) for isotope ratio measurements and 1.26-6.44% RSD for iron measurements. PMID- 2933092 TI - The regulatory role of adenosine activated T-lymphocyte subset on the immune response in humans. II. Adenosine induced expression of T8 antigen. AB - Adenosine sensitive suppressor T cells (ESen) were isolated from healthy donors and continuous cultures of these cells were established. It was found that the continuous proliferation of ESen cells required IL-2, Adenosine and ConA. The reactivity of ESen cells with OKT3, OKT4 and OKT8 monoclonal antibodies was studied before and after incubation with adenosine. The majority of freshly isolated ESen cells were OKT8+ cells. During culture, the majority of the proliferating ESen cells were OKT4; however, following a brief incubation of cultured ESen cells with adenosine, an increase in OKT8+ cells and a decrease in OKT4+ cells were observed. A fraction of ESen cells exhibited simultaneously OKT4+ and OKT8+ antigens similar to thymocytes. Furthermore, adenosine treatment of thymocytes resulted in a small increase in OKT8+ and OKT3+ cells and a parallel decrease in OKT4+ cells. These results indicate that adenosine may play a regulatory role in the differentiation of lymphocytes programmed to carry out a specific function. PMID- 2933093 TI - Initial filtration rate and initial clogging in the Hemorheometre. AB - The role of different factors contributing to red cell filterability in the Hemorheometre has been investigated. Although the original method uses a small volume of suspension to determine red cell filterability, the present experiments showed that the results obtained are still significantly affected by filter clogging. Consequently a change in filterability could be due to a change in filter clogging possibly by residual leucocytes. An adaptation of filter chamber and filling method is described, resulting in a simpler and faster measuring procedure. The inaccuracy in measuring low haematocrits contributes significantly to experimental errors. Therefore a definition of red cell filterability based on the red cell count (instead of haematocrit) of the suspension is suggested. PMID- 2933094 TI - [Effect of exogenous activation of kininogenesis on the functional morphology of the gastric fundal glands in experimental conditions]. AB - The experiments on Wistar rats have shown that activation of kinin-forming system with intraperitoneal kallikrein injection was accompanied by phase changes of enzyme activity responsible for acid, mucus and protein production in fundal gland cells of the stomach. PMID- 2933096 TI - [Occurrence of atypical histamine H2 receptors in the wall of the frog subclavian vein]. AB - Selective H2-histamine agonist dimaprit was shown to produce relaxation of the isolated frog subclavian vein, with it persisting under the effect of selective H2-histamine antagonist cimetidine. Possible nonspecific mechanisms of relaxation produced by histamine are discussed. The data presented do not exclude that there are atypical H2-histamine receptors in subclavian vein of frogs, the activation of which initiates the attenuation of the active tension. PMID- 2933095 TI - [Effect of diazepam, carbamazepine, sodium valproate and their combinations with vitamin preparations on epileptic activity]. AB - The anticonvulsive action of diazepam, carbamazepine, sodium valproate and their combinations with pyridoxal-5-phosphate, nicotinamide, and alpha-tocopherol were investigated in acute experiments on mice with corazole-induced seizures. Diazepam (0.5 mg/kg), carbamazepine (50 mg/kg) and sodium valproate (200 mg/kg) were shown to reduce convulsive intensity and lethality. Vitamins nicotinamide (250 mg/kg), pyridoxal-5-phosphate (10 mg/kg) and alpha-tocopherol (100 mg/kg) potentiated anticonvulsive action of the above antiepileptic drugs. The results of the investigation suggest the efficacy of pathogenetic therapy and give new evidence of the advisability of using vitamins in combination with synthetic anticonvulsive drugs. PMID- 2933097 TI - [Experimental analysis of the immunostimulant properties of vitamin A]. AB - The experiments on CBA mice and rabbits have shown that vitamin A injection to animals at a daily dose of 3000 and 200000 IU, respectively, stimulates the production of antibody-forming cells and antibodies upon immunization with sheep red blood cells, without affecting the immune response to Vi-antigen. Vitamin A blocks the generation of antigen-specific suppressors, having no effect on concanavalin A-induced suppressors. PMID- 2933098 TI - Identification and quantitation of protein S in human platelets. AB - Gel filtered human platelets contaminated with less than 0.02% of plasma protein S contained 490 ng of protein S antigen per 3 X 10(8) platelets, equivalent to 2.5% of protein S in whole blood. Three patients with heterozygous plasma protein S deficiency, a congenital disorder associated with venous thrombotic disease, had platelet protein S antigen levels that were 40% of the mean platelet level in ten normal volunteers. In immunoblotting analysis, platelet protein S was indistinguishable from plasma protein S. Thrombin stimulation of platelets caused release of 63% of total protein S antigen and this release was abolished when platelets were preincubated with metabolic inhibitors. Thrombin effected limited proteolysis of platelet protein S and this reaction was inhibited by calcium ions. Immunofluorescent staining of platelets using protein S antibodies demonstrated that protein S colocalized with fibrinogen, an established alpha granule protein. Thus, human platelets contain protein S in alpha granules that can be released by thrombin stimulation. The released protein S may bind to stimulated platelets and thereby promote and localize the anticoagulant activity of activated protein C on the platelet surface. PMID- 2933099 TI - Role of endothelium in the control of arterial diameter by blood flow. PMID- 2933101 TI - The expression of chick alpha A2-crystallin RNA during lens development and transdifferentiation. AB - During development of the vertebrate lens, the lens epithelium undergoes a final stage of differentiation into lens fibre cells, during which the major lens proteins, the crystallins, are synthesised. Lentoids, comprising clusters of lens fibre cells can also be produced by transdifferentiation from certain non-lens tissues, including neural retina and pigmented retinal epithelium. We have isolated an alpha A2-crystallin genomic probe and used it to study the transcription and processing of alpha A2-crystallin mRNA both during lens development and transdifferentiation. We relate these results to earlier measurements in this laboratory of delta-crystallin transcription and alpha- and delta-crystallin protein synthesis, to compare the expression of these two sets of genes. Tissue specific differences in gene expression were found. delta crystallin mRNA is transcribed before alpha A2-crystallin RNA in the lens, but after it in transdifferentiating neural retina and pigmented epithelia. PMID- 2933100 TI - Fibronectin and phagocytosis. PMID- 2933102 TI - Fibrillarin: a new protein of the nucleolus identified by autoimmune sera. AB - Autoimmune serum from a patient with scleroderma was shown by indirect immunofluorescence to label nucleoli in a variety of cells tested including: rat kangaroo PtK2, Xenopus A6, 3T3, HeLa, and human peripheral blood lymphocytes. Immunoblot analysis of nucleolar proteins with the scleroderma antibody resulted in the labeling of a single protein band of 34 kD molecular weight with a pI of 8.5. Electron microscopic immunocytochemistry demonstrated that the protein recognized by the scleroderma antiserum was localized exclusively in the fibrillar region of the nucleolus which included both dense fibrillar and fibrillar center regions. Therefore, we have named this protein "fibrillarin". Fibrillarin was found on putative chromosomal nucleolar organizer regions (NORs) in metaphase and anaphase, and during telophase fibrillarin was found to be an early marker for the site of formation of the newly forming nucleolus. Double label indirect immunofluorescence and immunoelectron microscopy on normal, actinomycin D-segregated, and DRB-treated nucleoli showed that fibrillarin and nucleolar protein B23 were predominantly localized to the fibrillar and granular regions of the nucleolus, respectively. RNase A and DNase I digestion of cells in situ demonstrated that fibrillarin was partially removed by RNase and completely removed by DNase. These results suggest that fibrillarin is a widely occurring basic nonhistone nucleolar protein whose location and nuclease sensitivity may indicate some structural and/or functional role in the rDNA-containing dense fibrillar and fibrillar center regions of the nucleolus. PMID- 2933103 TI - Rotation of the cell nucleus in living cells: a quantitative analysis. AB - Nuclear rotation is observed in a variety of cell types. However, few quantitative analyses are reported and the significance of this phenomenon is still unclear. To investigate this type of nuclear movement, we performed a quantitative analysis in mouse L-929 fibroblasts, a cell line chosen since it displays a high nuclear rotational activity. Analyses were performed using time lapse microcinematography. The relationship between nuclear rotation and other cellular phenomena such as the cell cycle and locomotion were studied. Then, we investigated the rotation in a population of sister cells to study whether it is genetically determined. Finally, we performed a qualitative analysis of nuclear rotation in different cultured cell lines. Results show that nuclear rotations preferentially occur during the phases of the cell cycle which surround mitosis. PMID- 2933104 TI - Twisted architectures in cell-free assembled collagen gels: study of collagen substrates used for cultures. AB - Reprecipitated fibrils from collagen solutions assemble into aggregates often showing a remarkable twisted structure. We first observed these aggregates in collagen gels prepared to facilitate culture of epithelial cells. We verified that these structures form in the absence of cells and correspond to a process of self-assembly. Studies on reconstructed fibrils of collagen are generally based on the examination of thin specimens mounted onto coated grids prepared for electron microscopy. We rather applied the classical methods of fixation, embedding and ultramicrotomy, which allowed us to analyze the structure of these aggregates, several microns in diameter. Our gels were prepared from 2.5 mg/ml tropocollagen solutions usually chosen for cell and organ cultures. The time required to obtain twisted architectures, in these aggregates, depends on temperature and the presence of factors such as fetal calf serum proteins. Twist is observed at two different levels of organization. Microfibrils are gathered into twisted bundles which condense into cross-striated fibrils. These fibrils themselves aggregate and show a mutual twist whose orientation is left-handed as is the twist observed within each microfibril bundle. Several models of these architectures are presented. Planar twist, cylindrical twist and toroidal twist are described and their relation to the structure of certain liquid crystals is considered. Examples of orthogonal packing also have been observed. These structures obtained in vitro are very close to patterns already described in vivo in numerous collagen matrices. PMID- 2933105 TI - Ultrastructural changes in the rat thyroid gland during iodine deficiency. AB - Thyroid ultrastructure changes were studied during the course of a low iodine diet in rats. At day 20, follicles were normal, but a number of them contained cells of higher density and with greatly elongated microvilli. Endoplasmic reticulum cisternae were frequently dilated. From day 20 until day 80, the most characteristic changes in the thyroid cells were the progressive accumulation of subapical peroxidase-positive exocytotic vesicles. After 80 days of the low iodine treatment, Golgi apparatuses were very active. Cell division could be observed. At this stage, exocytotic vesicles were generally very abundant. These data suggest that the remarkable accumulation of subapical exocytotic vesicles between day 20 and day 120 might represent an adaptation to the moderate and gradual increase in TSH stimulation that occurs in the conditions of low iodine diet. PMID- 2933106 TI - Osmium impregnation of the endoplasmic reticulum correlates with the functional status of prostatic secretory cells. AB - The ultrastructure of prostatic secretory cells was studied with the osmium impregnation technique in order to determine if the ER reactivity, or its absence, and its three-dimensional organization correspond to specific functions possibly hormono-dependent. Thick sections (0.3 micron) of rat ventral prostate were made after a five-day impregnation with osmium tetroxide and examined by standard transmission electron microscopy at 80 kV. Studies were performed in normal adult rats, between the 3rd and 26th day following castration and in castrated rats treated with 5-alpha-dihydrotestosterone. In normal rats the impregnation technique delineated three secretory cell types (dark, greyish and clear), representing various degrees of reactivity in ER cisternae; however, despite this quantitative variation, they had similar morphological characteristics. In a longitudinal section, the ER network appeared to be made of saccules running parallel along the length of the cell and forming whorl-like patterns around the nucleus. Comparison of sections taken at various angles suggests that the ER network is made of concentric parallel saccules extending from the base to the apex of the cell and encircling the nucleus and the Golgi apparatus like a large multilayered cylinder. Whereas in dark cells the Golgi apparatus contained mostly clear vesicles, it was always heavily impregnated in clear cells. Noteworthy, osmium deposits were rarely observed on the nuclear envelope of secretory cells but were always present in basal cells. After castration, secretory cells became progressively cubic and the most conspicuous cytoplasmic change was observed in association with the ER. The Golgi apparatus decreased markedly in volume and became heavily stained with metallic osmium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2933107 TI - Renewal of Leydig cells in the neonatal and adult monkey: a radioautographic study. AB - The populations of interstitial cells in the testis of three 2-3 month old monkeys and of three 5-6 years old adults (Macaca fascicularis) were analyzed: percentage, mitotic index and labeling index after 3H-thymidine injection. In the young monkey and the adult well differentiated Leydig cells incorporate the precursor as fibroblast-like cells. This demonstrates their ability of renewal. PMID- 2933108 TI - Three-dimensional analysis of fibrillar centers and associated chromatin in the nucleolus of human oocytes in primordial follicles. AB - The intranucleolar localization of fibrillar centers and their relationships with nucleolus-associated chromatin were determined in stereopairs of human oocyte nucleoli obtained by computer reconstruction of serial sections. This study showed that there was no numerical relationship between the number of fibrillar centers and the number of chromosomal NORs. The three-dimensional reconstruction demonstrated that the majority of fibrillar centers was directly connected with the nucleolus-associated chromatin. PMID- 2933109 TI - Monoaminergic involvement in the pharmacological actions of buspirone. AB - Buspirone, MJ-13805 and MJ-13653 did not produce a '5-hydroxytryptamine (5-HT) syndrome' in rats at doses up to 20 mg kg-1. These drugs were very weak 5-HT uptake blockers (IC50 much greater than 10 microM) compared to drugs such as chlorimipramine. These drugs did not inhibit either monoamine oxidase (MAO)-A or MAO-B. The Ki values for these agents as inhibitors of [3H]-5-HT and [3H] ketanserin binding to rat frontal cortex or hippocampal membranes were in the microM range, well above the brain concentrations achieved after an oral dose of 25 mg kg-1. Parenterally administered buspirone blocked apomorphine-induced stereotypy, inhibited the 5-HT syndrome elicited by 5-methoxy-N,N dimethyltryptamine, and delayed the onset of p-chloroamphetamine induced behaviours. PMID- 2933111 TI - The effect of a calcium antagonist, nitrendipine, on the responses of isolated strips of human, chorionic plate artery to prostaglandins E2 and E1. AB - Six point concentration-response curves were established for the contractile effect of prostaglandin E2 (PGE2) on helically-cut strips of human chorionic plate arteries. Tissues were then allocated to one of four treatment groups: a control group and 3 groups exposed to the calcium channel blocker nitrendipine at 10(-9), 10(-7) or 10(-5) M. The concentration-response curves were then repeated. The addition of nitrendipine was associated with a significant depression of the induced contraction. The contractile response to the lower doses of PGE2 was replaced by a small relaxation in 63% of the treated tissues. It is suggested that in these tissues PGE2 exerts its constrictor effect via the receptor operated channels and that nitrendipine is blocking this effect. Similar experiments performed with PGE1 showed great variability in the initial response. Nitrendipine 10(-5) M failed to exert any detectable effect on this response. Pregnancy-induced hypertension is associated with vasoconstriction in both the maternal and placental circulations. There also appears to be a relative excess of vasoconstrictor eicosanoid production. Nitrendipine may be of use in the treatment of this condition. PMID- 2933110 TI - A comparison of 5-hydroxytryptamine receptors mediating contraction in rabbit aorta and dog saphenous vein: evidence for different receptor types obtained by use of selective agonists and antagonists. AB - Using recently available selective agonists and antagonists we have examined further our postulate (Apperley et al., 1980) that 5-hydroxytryptamine (5-HT) mediates contraction of dog saphenous vein via a different 5-HT receptor type from that in the rabbit aorta. In the rabbit isolated aorta, ketanserin and spiperone were potent, specific, competitively-acting antagonists of the contractile effects of 5-HT. In contrast, in the dog isolated saphenous vein neither ketanserin nor spiperone caused any rightward displacement of concentration-response curves to 5-HT although the maximum response was reduced by about 10%. In the rabbit aorta 5-carboxamidotryptamine (5-CONH2-T) was a weak agonist whilst the 5-N,N-dimethyl and 5-N-ethyl derivatives were even weaker or inactive. The contractile effect of 5-CONH2-T in the rabbit aorta was potently and competitively antagonized by ketanserin. In contrast, in the dog saphenous vein 5-CONH2-T and its 5-N,N-dimethyl and 5-N-ethyl derivatives were all potent agonists. The contractile effect of 5-CONH2-T was not markedly affected by ketanserin. The profile of action of ketanserin and spiperone in the rabbit aorta is consistent with the view that 5-HT2 receptors mediate contraction in this preparation. However, the 5-HT receptor mediating contraction in the dog saphenous vein appears to be '5-HT1-like', sharing a number of characteristics with the 5-HT1 recognition site identified from [3H]-5-HT ligand binding studies in brain tissue. PMID- 2933112 TI - Ageing in Down's syndrome. AB - In a group of 23 hospital patients aged over 50 with Down's syndrome, psychological testing indicated that significant intellectual deterioration, which was un-related to chronological age, sex, length of hospitalisation, or earlier mental age, had occurred in nine. Clinically, there was no evidence in any patient of active physical illness, focal neurological signs, or dementia, but significant associations were found between intellectual deterioration and decreased visual acuity, hearing loss, and macrocytosis. PMID- 2933113 TI - Pica as a feature of autism. PMID- 2933114 TI - Is mania incompatible with Downs syndrome. PMID- 2933115 TI - Percutaneous transluminal angioplasty for renal branch stenosis--a report on a six-year-old boy. PMID- 2933116 TI - A simple method for limiting angioplasty catheter balloon pressures. AB - Percutaneous angioplasty catheter balloons may rupture if over-inflated. Balloon inflation pressures are not always measured. We describe a simple and inexpensive method for limiting balloon inflation pressures, using no additional equipment. PMID- 2933117 TI - Peroxy free radicals, enzymes and radiation damage: sensitisation by oxygen and protection by superoxide dismutase and antioxidants. AB - In vitro studies have shown that in the presence of the DNA base thymine, the enzyme alcohol dehydrogenase can be extensively damaged by exposure to only 1 gray of cobalt-60 gamma radiation. When irradiated solutions are purged with oxygen-free nitrogen or contain the enzyme superoxide dismutase or various antioxidants, the extent of inactivation of the dehydrogenase is considerably reduced. Peroxy free radicals are considered to be responsible for the inactivation and cysteine and methionine residues are considered the most likely sites of initial damage. The results presented, with those obtained with ADP and urate instead of thymine and with various amino acids and foreign compounds, are discussed in the light of previous statements concerning the relevance of enzyme damage in radiobiology and the role of oxygen free radicals in tissue injury generally. PMID- 2933118 TI - An investigation of the radiation dose to staff during cardiac radiological studies. AB - Measurements of radiation distributions in the vicinity of the couch were undertaken for a number of projections commonly employed during cardiac radiological studies. Three types of investigations were considered; cardiac catheterisations, pacemaker implants and percutaneous transluminal coronary angioplasties. The radiation dose to staff involved in these procedures was estimated. For each group of staff, the maximum annual workload and the workload which would necessitate an individual becoming a classified radiation worker may be deduced from an expression given in the text. PMID- 2933119 TI - Acne: double blind clinical and laboratory trial of tetracycline, oestrogen cyproterone acetate, and combined treatment. AB - Since the recent introduction of a drug regimen containing 2 mg of the antiandrogen cyproterone acetate and 50 micrograms ethinyl-oestradiol (Diane; oestrogen-cyproterone acetate) several uncontrolled reports have extolled the benefits of this drug. Double blind studies, however, are lacking. Sixty two patients with moderate or moderately severe acne were therefore included in a double blind trial of treatment for six months comparing tetracycline alone, oestrogen-cyproterone acetate alone, and a combination of these agents. Sebum excretion rates and bacterial counts were measured before, during, and after treatment, at the same time as a clinical assessment was made. At six months the acne (as assessed by overall grade) had improved by 68% in the antibiotic treated group and by 74% in the oestrogen-cyproterone treated group. The group given a combination of both agents improved by 82%, which was significantly better (p less than 0.025) than the improvement in the tetracycline treated patients. No significant difference was found between the groups given oestrogen-cyproterone alone and the combined treatment. The sebum excretion rate was suppressed by 25% in the patients in both groups receiving oestrogen-cyproterone but not in the group given antibiotics alone. Oestrogen-cyproterone acetate is as effective as antibiotics in treating acne in women, and adding antibiotics offers no advantage over using oestrogen-cyproterone on its own, although in this study the combination was more effective than tetracycline alone at six months. PMID- 2933120 TI - Alpha atrial natriuretic peptide concentrations in plasma of children with congenital heart and pulmonary diseases. PMID- 2933121 TI - Palmoplantar pustulosis and smoking. PMID- 2933122 TI - Importance of early tumour exacerbation in patients treated with long acting analogues of gonadotrophin releasing hormone for advanced prostatic cancer. PMID- 2933123 TI - Neurotensin in human brain: regional distribution and effects of neurological illness. AB - The regional distribution of neurotensin-like immunoreactivity was investigated in normal human brain and in brains of patients who had died with neurological illness. In Huntington's disease, neurotensin was increased in the pallidum, whilst in Parkinson's disease no significant changes in neurotensin content were observed. Similarly no changes were found in the telencephalic neurotensin content in senile dementia of the Alzheimer type. High levels of neurotensin-like immunoreactivity were detected in lumbar cerebrospinal fluid from patients and the characterization of the immunoreactive material by high-performance liquid chromatography showed it to be indistinguishable from synthetic neurotensin. PMID- 2933124 TI - Diuresis and reduction of salt appetite by lateral ventricular infusions of atriopeptin II. AB - Infusions of 60 pmol/h atriopeptin II into the lateral ventricles stimulated urine flow in both normally hydrated and sodium depleted conscious rats without any increase in the excretion of sodium, potassium or total solutes. The urinary sodium concentration and osmolality both declined significantly. In addition to the renal effects, cerebroventricular infusions of 60 pmol/h atropeptin II reduced salt appetite in rats following depletion of sodium by combined treatment with furosemide diuresis and low sodium diet. Neither 60 nor 600 pmol/h doses had any effect on urine volume or concentration during intravenous infusions, so the effects appear to be mediated by the central nervous system (CNS). Atriopeptins may act through the CNS to facilitate reduction of extracellular volume in synergy with peripheral natriuresis: by increasing urine flow independently from natriuresis; and by restricting further expansion of extracellular volume by reducing salt appetite. PMID- 2933125 TI - The action of centrally administered arginine vasopressin on blood pressure in the conscious rabbit. AB - In addition to its peripheral endocrine actions, arginine vasopressin (AVP) has been implicated in the central control of blood pressure. Intracerebroventricular (i.c.v.) injections (0.01-1.0 nmol) of AVP or arginine vasotocin (AVT), but not oxytocin (OXY), into unanesthetized rabbits caused a rapid, dose related rise in blood pressure as well as increases in heart rate. The lowest centrally administered dose of AVP and AVT (0.01 nmol) had no effect on blood pressure when given intravenously. In search of tissue locus for the pressor effect of AVP microinjection of AVP and OXY into the posterior hypothalamus and septum of conscious rabbits was without effect. However, microinjection (0.01-0.04 nmol) of AVP into the nucleus tractus solitarius of anesthetized rabbits caused a rise in blood pressure similar to the response seen after i.c.v. injection. Comparable volumes of the vehicle into the ventricle or the tissue sites had no effect on resting blood pressure. The pressor response after AVP given i.c.v. was significantly reduced up to 3 h after administration of the ganglionic blocker, chlorisondamine HCl. The central antagonist, d(CH2)5Tyr (Me) vasopressin, eliminated the usual increase in blood pressure after administration of AVP in half the animals tested. The results indicate that AVP acts centrally to mediate cardiovascular responses in unanesthetized as well as anesthetized rabbits. PMID- 2933126 TI - Characteristics of feeding induced by the serotonin agonist 8-hydroxy-2-(di-n propylamino) tetralin (8-OH-DPAT). AB - The effects of the putative serotonin agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) on food intake in freely-feeding and food deprived rats were examined. In freely-feeding rats, low doses of 8-OH-DPAT (15-60 micrograms/kg) significantly increased food intake without affecting drinking, grooming, rearing or locomotion. Higher drug doses (125-4000 micrograms/kg) also produced feeding and caused locomotor stimulation and serotonin-related stereotyped behaviour (i.e., forepaw padding, headweaving, wet dog shakes, flat body posture). When feeding and stereotypy were observed concurrently, response competition was evident and feeding behaviour was fragmented into numerous short eating bouts. As drug-induced stereotypy declined with time, this fragmented pattern of eating was succeeded by long bouts of eating which were similar to those observed at doses of 15-60 micrograms/kg 8-OH-DPAT. In 24 hr food deprived rats, low doses of 8-OH DPAT had no effect on food intake. However, high doses of 8-OH-DPAT (250-4000 micrograms/kg) decreased feeding in food deprived animals, an effect which was probably secondary to the induction of stereotypy. It is proposed that the behavioural effects of 8-OH-DPAT may be explained by a dual effect on brain serotonergic mechanisms, which is dose dependent. Thus, low doses of the drug may preferentially activate inhibitory presynaptic serotonin receptors (autoreceptors), decrease serotonin metabolism and thereby increase feeding. In contrast, high doses of 8-OH-DPAT appear to stimulate postsynaptic serotonin receptors and thus produce stereotypy. Alternatively, it is possible that 8-OH DPAT may elicit feeding by postsynaptic serotonin receptor blockade. PMID- 2933127 TI - Analysis of dopamine D1 and D2 receptor involvement in d- and l-amphetamine induced anorexia in rats. AB - The concept of dopamine receptor subtypes and the recent development of selective dopamine receptor agonists and antagonists raises the possibility of specific subtype involvement in amphetamine-induced anorexia, and, furthermore, provides the means to evaluate the possibility. Using a test of palatable food consumption by nondeprived male rats, our data confirmed a more potent suppressant effect of d-amphetamine on food intake, compared to l-amphetamine (potency ratio 5.32:1). The test proved sensitive, with ED50s of 0.28 mg/kg and 1.49 mg/kg for d- and l amphetamine, respectively. The modest anorectic effect of 0.3 mg/kg d-amphetamine was completely reversed by the selective dopamine D1 receptor antagonist, SCH 23390, but was not affected by the selective D2 receptor antagonist, sulpiride. A matched feeding-suppressant effect of 1.0 mg/kg l-amphetamine was reversed at one dose of SCH 23390, but was unaffected by sulpiride. Stronger anorectic effects produced by 1.0 mg/kg d-amphetamine and 3.0 mg/kg l-amphetamine were not antagonized either by SCH 23390 or sulpiride. The selective D1 receptor agonist, SKF 38393, produced a dose-dependent reduction in food consumption, without producing behavioural stereotypy. Unlike amphetamine, SKF 38393 is not self administered, and therefore may provide an example of a novel pharmacological dissociation between anorectic and reinforcing effects of drug treatments mediated by dopamine receptors. Our data implicate dopamine D1 receptors in the control of feeding responses, and suggest that these receptors may mediate the anorectic effect of small-dose amphetamine treatments. PMID- 2933128 TI - Atypical indolamine-immunoreactive cell groups in the dorsal myelencephalon of the rat. AB - The presence of atypical indolamine-immunoreactive (IAI) neurones in the dorsal myelencephalon of the rat was demonstrated by means of peroxidase-antiperoxidase (PAP) immunocytochemistry. Besides the area postrema, two other regions, viz. the solitary complex and the superficial rostral cuneate fascicle, were found to contain neuronal perikarya displaying a normally weak staining which was markedly enhanced after monoaminoxidase (MAO) inhibition. In contrast to immunoreactive cells of the periaqueductal central gray, the dorsal myelencephalic IAI neurons were undetectable after serotonin synthesis inhibition with p-chlorophenylalanine (PCPA), as were immunoreactive terminal neuropils in most brainstem areas. However, sequential treatment with the MAO inhibitor, iproniazid, completely reversed the PCPA-induced suppression of perikaryal immunoreactivity and partially restored axonal staining. None of the atypical cell groups displayed a detectable formaldehyde-induced specific histofluorescence. Since brain levels of tryptamine are likely to increase significantly after MAO inhibitor/PCPA treatment, and furthermore tryptamine can be assumed to cross-react with serotonin, it is suggested that the observed atypical IAI neurons may represent either a subpopulation of serotoninergic neurons; previously postulated true tryptamine neurons; or non-indolaminergic neurons endowed with a selective uptake mechanism for serotonin or tryptamine. These results corroborate the view that different types of indolamine neurons exist in the rat brainstem. Moreover, they underscore the need for cautious interpretation of serotonin neuron mapping studies involving the use of MAO inhibitors. PMID- 2933129 TI - Inhibition of spontaneous or angiotensin II-stimulated water intake by atrial natriuretic factor. AB - A family of peptides, known as atrial natriuretic factors (ANF), have been isolated from atrial muscle tissue and reported to have profound effects on water and salt metabolism. ANF have also been reported to be present in the brain. The primary actions of these peptides lead to a reduction in plasma and extracellular fluid volume by eliciting natriuresis and diuresis, and by opposing the action of other peptidergic systems such as the vasopressin and angiotensin systems that promote water retention and enhance drinking behavior. This study was designed to determine if, in addition to its peripheral actions, ANF would also affect water ingestion, a mechanism that would be consistent with its general actions as a factor regulating extracellular fluid volume. Intraventricular (IVT) administration of an ANF, atriopeptin III (APIII), to intact male rats resulted in a significant inhibition of water intake in animals which were conditioned to drink during a one hour period. The inhibitory effects of APIII were immediate and most effective during the first 15 minute period, when maximal drinking occurred. Most remarkably, APIII given IVT also inhibited the potent dipsogenic action of angiotensin II (AII) on both water and a 2% NaCl solution intake. The results strongly suggest that ANF may have a significant role in central regulation of fluid intake and that its antidipsogenic effects may be mediated, at least in part, by an inhibitory effect on the central action of AII. PMID- 2933130 TI - [Determination of the pre-excitation focus in the W-P-W picture using electrocardiographic methods]. PMID- 2933131 TI - [Glycosylation of glycoconjugates in alloplastic arterial prostheses]. PMID- 2933132 TI - [Formation of Langerhans granules seems linked to membrane ATPase activity of epidermal Langerhans cells]. AB - The epidermis contains a population of dendritic cells, Langerhans cells (LC), derived from cells originating from bone marrow, bearing receptors for the Fc fragment of IgG and for the C3 fraction of complement and expressing at their surface Ia antigens of the major histocompatibility system. These cells with multiple immunological functions are capable of presenting antigens to immunocompetent cells. The labeling of LC through revelation of their membranous ATPase activity constitutes one of the best available techniques for their visualization. Moreover, the presence of this ATPase activity appears to be a prerequisite for the induction of contact sensitivity, since in the absence of such activity, the epicutaneous application of a hapten induces a state of immunological tolerance. Applying, at a sensitizing dose, 2,4 dinitrofluorobenzene (DNFB) on an untreated guinea-pig skin surface results in a momentary drop in the number of ATPase positive LC in the application zone. Using an improved technique for ATPase labeling (Hanau et coll. submitted for publication, 1985)--which allows one to extend the study from optical to electron microscopy--we observed by electron microscopy the formation, within the LC, of numerous Langerhans granules, concurrent with the loss of ATPase membranous activity. These granules, first described by Birbeck et coll. and specific to LC in the epidermis, have a complex structure. On a section, they may display either a linear aspect (rod-like)--with sometimes a vesicular portion at one extremity (racket-like)--or a circular shape. Whatever their shape, they always show a central striation, which gives them a zipper-like appearance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2933133 TI - Muscular adaptations to exercise and training. AB - This article provides an overview of the characteristics of skeletal muscle, with an emphasis on equine skeletal muscle. A discussion of many of the adaptive processes that can occur in this tissue in response to altered states of physical activity is also included. PMID- 2933134 TI - Trypsin digestion of bovine cardiac troponin C in the presence and absence of calcium. AB - The rate of tryptic digestion of cardiac troponin C (cTNC) has been shown to be dependent on Ca2+ as was noted earlier for skeletal TNC (sTNC). Two representative peptides have been characterized on the basis of amino acid composition and partial amino terminal sequence analysis. Circular dichroism and fluorescence studies monitored their response to the presence of Ca2+. Their ability to form complexes with the ATPase inhibitory subunit of cardiac troponin (cTNI) was determined by urea - polyacrylamide gel electrophoresis and fluorescence experiments. The ability of these peptides to substitute for whole cTNC in restoring the ATPase activity of a partially inhibited synthetic actomyosin system was also explored. The N-terminal peptide 1-88 already contains a large amount of ordered structure, which indicates that the alpha-helices flanking binding site II of cTNC exist independently of Ca2+. Consequently this peptide shows limited increase in structure in the presence of Ca2+. It binds to cTNI independently of the presence of Ca2+ and could substitute for whole cTNC by relaxing the inhibitory effect of cTNI. The C-terminal peptide 103-158 has a low amount of secondary structure in the absence of Ca2+ but this increases dramatically in the presence of this cation. This peptide could only form a stable complex with cTNI in the presence of Ca2+ and was unable to release the inhibitory effect of cTNI. PMID- 2933135 TI - Substrate binding properties of the human liver hexosaminidase A activator protein. AB - The human liver hexosaminidase A activator protein has been shown to bind to the substrate GM2 ganglioside by cosedimentation in sucrose density gradients. Among other proteins tested only serum albumin forms a GM2 ganglioside - protein complex. Both activator protein and albumin bind to the monomeric form of GM2 ganglioside and not to the micellar form of the substrate. The GM2 ganglioside - activator protein complex can be recovered in a stable form. Storage at various temperatures or incubation with monosaccharides or with detergent does not result in dissociation of the complex. GM2 ganglioside in the activator-substrate complex is exchangeable with exogenous GM2 ganglioside. Hexosaminidase A, prepared from human liver, hydrolyzes GM2 ganglioside in the activator-substrate complex as efficiently as GM2 ganglioside supplied exogenously. The activator - GM2 ganglioside complex forms at pH 3.0 and exhibits an optimum similar to the pH optimum of hexosaminidase A catalyzed hydrolysis of GM2 ganglioside in the presence of the activator; however, the ability of the activator to stimulate enzymic hydrolysis of substrate is rapidly lost after heating at 75 degrees C, whereas its ability to bind substrate is increased. The sphingolipids cerebroside sulfate and sphingomyelin show little or no binding to the hexosaminidase A activator protein nor do they inhibit activation of hexosaminidase A catalyzed hydrolysis of GM2 ganglioside. By contrast GM1 ganglioside inhibits both substrate binding and enzyme activation. PMID- 2933136 TI - Accutane-induced teratogenesis. PMID- 2933137 TI - The dilemma of wrongful birth, wrongful life. Interview by Bill trent. PMID- 2933138 TI - Pilot study of intra-arterial floxuridine, mitomycin and doxorubicin in combination with degradable starch microspheres to treat primary and metastatic tumors of the liver. AB - Concurrent administration of degradable starch microspheres and cytostatic agents into the hepatic artery results in decreased systemic exposure and increased hepatic exposure to drug compared to intra-arterial administration of drug alone. Degradable starch microspheres 210 mg/m2 mixed with floxuridine 500 mg/m2, doxorubicin 40 gm/m2, and mitomycin 10 mg/m2 were administered through hepatic artery catheters to eleven patients with primary or metastatic cancer of the liver. Toxicity was acceptable and consisted of severe myelosuppression (5%), duodenal/gastric ulceration (9%), mild to moderate nausea and vomiting (17%) and alopecia (86%). There were no responses among the eleven patients; 7 of 7 patients with colo-rectal carcinoma had stable disease while on study. Minimal activity was observed in 7 patients with colo-rectal carcinoma. The use of degradable starch microspheres offers a new approach to the regional treatment of cancer and warrants further study. PMID- 2933139 TI - Metabolism and biliary excretion of trimetrexate by the isolated perfused rat liver. AB - The metabolism and biliary excretion of trimetrexate (TMTX), a lipid soluble antifolate, were examined using a recirculating isolated perfused rat liver system. Elimination of TMTX into perfusate was biphasic and dose-independent, with distribution and elimination half-lives of 2 and 13 min. Two metabolites, M1 and M2, both known to inhibit dihydrofolate reductase activity, were present in perfusate only in small concentrations. However, of the total TMTX dose, approximately 50% was excreted in bile as M1, and 20% as M2. Up to 75% of the total dose was accounted for as TMTX, M1, or M2 in perfusate and bile. PMID- 2933140 TI - Selective toxicity of neocarzinostatin-monoclonal antibody conjugates to the antigen-bearing human melanoma cell line in vitro. AB - Monoclonal antibodies (IgG1) against high molecular weight antigen A-1-43 on human melanoma cell line A-375 were successfully linked to the anti-tumour protein neocarzinostatin (NCS) using the heterobifunctional reagent N succinimidyl 3-(2-pyridyldithio)-propionate (SPDP). The conjugate retained both the reactivity of the antibody and the toxicity of the drug. The antigen-bearing cell line A-375, antigen-lacking cell line MeWo and normal skin fibroblasts were exposed to NCS-monoclonal antibody conjugates. As negative control, cells were also treated with free NCS and NCS coupled to normal mouse IgG1 antibodies. Inhibition of 3H-thymidine uptake after treatment was used to measure the biological activity of the cytotoxic drug complex or substance, respectively. Comparing the inhibition dose for 50% uptake (ID50) it was found that the monoclonal antibody-drug complex is about 100 times more toxic for the antigen bearing cell line than free NCS or normal mouse IgG1-NCS. This high toxicity is due to a local increase of drug concentration on these cells. With the two cell lines lacking the appropriate antigen no significant differences in the ID50 values were observed. A selectivity factor of 40-50 was obtained by comparing the cytotoxic effect of the monoclonal antibody-NCS conjugate upon the antigen bearing as opposed to the antigen-lacking cell type. These data demonstrate, that the toxicity of NCS can be directed by monoclonal antibodies to human tumour cells carrying the corresponding surface antigen. PMID- 2933142 TI - Effect of melphalan in vitro on induction of murine suppressor T cells by ConA. AB - The effect of treatment with melphalan in vitro on the activity of spleen cells from BALB/c mice was investigated. Incubation of spleen cells with 1.5-5 micrograms melphalan/1 X 10(7) inhibited subsequent mitogenic stimulation by ConA or PHA and the allogeneic response of BALB/c spleen cells against C57B1 target spleen cells. Incubation of spleen cells with ConA led to induction of suppressor T cells which when added to fresh cultures inhibited the allogeneic response. Preincubation of spleen cells with melphalan even at low concentrations (0.15-0.5 micrograms 1 X 10(7) cells) which do not directly affect mitogenic stimulation or allogeneic response partially inhibited the generation of suppressor T cells by ConA. Treatment with melphalan had no effect on already induced suppressor T cells as shown by incubation of spleen cells with melphalan (0.15-5 micrograms/1 X 10(7) cells) after incubation with ConA. Addition of cells treated with melphalan alone (without ConA) to fresh cultures led to an increase in the allogeneic response. PMID- 2933143 TI - Induction by X-irradiation of adenosine triphosphatase-deficient islands in the rat liver and their characterization. AB - The potential of X-rays to induce preneoplastic lesions in the rat liver was studied in order to clarify the reason why X-rays are ineffective in inducing hepatocellular carcinoma in this animal. Male newborn rats at 8 or 22 days of age received whole body X-ray irradiation of 100 to 400 rads. After weaning they were fed either basal diet or a diet containing 0.05% phenobarbital as a promoter. X rays induced numerous adenosine triphosphatase-deficient islands appearing in the liver by wk 22 of age. However, they were generally small, gamma-glutamyl transpeptidase-negative, and did not clearly respond to the promoting stimulus of phenobarbital. No hepatic tumors were observed by 22 mo after radiation, even in phenobarbital-treated animals. Thus the X-ray-induced enzyme-altered islands differ somewhat qualitatively from those induced by potent hepatic carcinogens and their preneoplastic potential if at all present may be very low. Similarities between these X-ray-induced lesions and some types of spontaneous enzyme-altered islands are pointed out. PMID- 2933144 TI - Jejunal blood flow after exposure to light in rats injected with hematoporphyrin derivative. AB - Experiments were performed to determine the effect of hematoporphyrin derivative (HPD) photodynamic therapy on blood flow to normal rat intestine. A segment of rat jejunum was exposed to red (greater than 590 nm) light (200 mW/cm2) 24 h after the i.v. administration of HPD. Blood flow to the light exposed segment was determined using the radioactive microsphere technique while blood flow to an adjacent light shielded segment of intestine served as an internal control. Animals were divided into six groups of six each: Group I, no HPD, no light; Group II, light, no HPD; Group III, HPD (20 micrograms/g body weight), no light; and Group IV, HPD (20 micrograms/g body weight), light. Blood flow in these four groups was determined 10 min after completion of a 30-min exposure to light. Only in Group IV was there a statistically significant decrease (P less than 0.005) in blood flow to the segment treated with HPD and light. In Groups V [HPD (20 micrograms/g body weight), light] and VI [HPD (10 micrograms/g body weight), light] blood flows were determined 24 h after exposure to light. In both of these groups there was also a significant (P less than 0.05) decrease in blood flow in the segment treated with HPD and light. This study demonstrates that normal intestinal blood flow can be disrupted by HPD photodynamic therapy. PMID- 2933141 TI - The augmentation of tumor-specific immunity using haptenic muramyl dipeptide (MDP) derivatives. I. Synthesis of a novel haptenic MDP derivative cross-reactive with Bacillus Calmette Guerin and its application to enhanced induction of tumor immunity. AB - A new haptenic compound, a muramyl dipeptide (MDP) derivative (designated as L4 MDP-ONB) cross-reactive with Bacillus Calmette Guerin (BCG) was synthesized. The cross-reactivity of L4-MDP hapten to BCG was demonstrated from the following evidence; (a) lymph node cells from BCG-primed C3H/HeN mice exhibited appreciable L4-MDP-specific proliferative responses to the in vitro stimulation of L4-MDP modified syngeneic cells (L4-MDP-self); (b) inoculation of L4-MDP-self into footpads of BCG-primed C3H/HeN mice elicited ample delayed type-hypersensitivity (DTH) responses in vivo as measured by footpad swelling; and (c) BCG-primed mice contained L4-MDP-reactive helper T cell activity which functions to augment the generation of effector T cell responses to cell surface antigens. This crossreactivity between L4-MDP hapten and BCG as measured by the helper T cell activity was applied to enhanced induction of tumor-specific immunity. When BCG primed C3H/HeN mice were immunized with L4-MDP-modified syngeneic X5563 tumor cells, these mice could generate augmented tumor-specific in vivo protective (tumor neutralizing) immunity as well as in vitro cytotoxic T cell responses. These results indicate the effectiveness of L4-MDP hapten in augmenting tumor specific immunity. The present approach is discussed in the context of potential advantages of this new hapten for its future application to clinical tumor systems. PMID- 2933145 TI - Pharmacokinetics of trimetrexate (NSC 352122) in monkeys. AB - The pharmacokinetics of trimetrexate was studied in Rhesus monkeys following i.v. bolus, continuous i.v. infusion, oral, and subcutaneous administration. Two methods were used to measure drug concentration in plasma, cerebrospinal fluid (CSF), and urine: the dihydrofolate reductase inhibition assay, and a reverse phase high-pressure liquid chromatography assay. The pharmacokinetic behavior of trimetrexate was characterized by triexponential plasma disappearance, elimination primarily by biotransformation, substantial plasma protein binding, poor CSF penetration, and limited oral bioavailability. Methotrexate, administered in an equimolar dose for comparison, was cleared more rapidly from plasma than was trimetrexate. Trimetrexate concentration remained above 0.1 microM 3-fold longer. In contrast to methotrexate, which is cleared almost exclusively by renal excretion, renal clearance of trimetrexate accounted for less than 5% of total clearance. A significant discrepancy was observed in plasma and urine trimetrexate concentrations measured by the two assay methods. The dihydrofolate reductase inhibition assay gave results approximately 2- to 4-fold higher in plasma. Two metabolites of trimetrexate which inhibit dihydrofolate reductase were identified in urine (one was also found in plasma) and appear to account for the different results obtained by the two assays. These metabolites would probably also interfere with the competitive protein binding assay currently being used to measure trimetrexate in ongoing phase I trials. PMID- 2933146 TI - A new cancer marker: a possible cancer screening method based on the suppression of phosphofructokinase by sera from cancer patients. AB - Sera from cancer patients specifically suppressed phosphofructokinase (fructose-6 phosphate kinase [PFK], EC 2.7.1.11), a rate-limiting enzyme in the glycolysis pathway. Among 418 cancerous sera, 68.7% evidence suppression; there was no organ specificity. Among 42 sera from early gastric cancer patients, 29 (69.0%) were positive, as were advanced gastric cancer, 14/19 (73.3%) pancreas cancer, and 75/101 (74.3%) lung cancer sera. In contrast 6/50 (12.0%) sera from patients with gastroduodenal ulcer, 3/23 (13.0%) with myoma uteri, and 0/6 with lung tuberculosis were positive. Patients with diabetes mellitus and those receiving steroid hormone therapy showed strong positive suppression. Comparative studies using other tumor markers (immunosuppressive acid protein, carcinoembryonic antigen, alpha-fetoprotein, beta 2-microglobulin, and ferritin) and the same sera used from PFK assay showed that the PFK method was two to three times more sensitive. Sephadex G-200 column chromatography revealed that the PFK-suppressive activity was retained in the postalbumin fraction. The PFK method may represent a promising new cancer screening method. PMID- 2933147 TI - [Left ventricular thrombosis in a case of daunomycin cardiomyopathy]. PMID- 2933148 TI - [Current problems in diabetic cardiopathy]. PMID- 2933149 TI - [Regression of hypertrophy of the left ventricle in hypertensive subjects treated with captopril]. PMID- 2933150 TI - Maltotriitol inhibition of maltose metabolism in Streptococcus mutans via maltose transport, amylomaltase and phospho-alpha-glucosidase activities. PMID- 2933151 TI - Isolation of newt lung ciliated cell models: characterization of motility and coordination thresholds. AB - Demembranated ciliated cell models are useful for studying mechanisms responsible for the regulation of ciliary coordination and waveform. This paper describes procedures for isolating ciliated cells from the newt, Taricha granulosa, by trypsin dissociation, their subsequent demembranation by Triton X-100, and their reactivation with MgATP to produce highly motile, coordinated, ciliated cell models. Reactivation of cell models with a high degree of mechanochemical coupling depended on avoiding mechanical damage and maintaining optimal conditions during all stages of isolation and reactivation. Highly motile models were prepared from cells incubated in trypsin, treated briefly with EDTA, separated by gentle agitation, and concentrated by centrifugation at low gravitational forces. Optimal demembranation and reactivation conditions were similar to those described previously for isolated newt lung axonemes. Under these conditions, nearly 100% of the models were reactivated when provided with MgATP and 90-95% beat with coordinated waves. The ciliary tufts beat at frequencies within the range measured in living cells and their reactivated motility was stable for at least 30 min at constant MgATP. These highly coupled models were used to show (1) that development of coordination in the ciliary tuft occurs at a higher substrate concentration range (10-25 microM) than that required to initiate motility per se (2-10 microM; (2) that outer dynein arms may not contribute to beat frequency at substrate concentrations below 35 microM; and (3) that vanadate has effects both on beat frequency and coordination of the tufts. PMID- 2933152 TI - Newt lung ciliated cell models: effect of MgATP on beat frequency and waveforms. AB - Highly coupled newt lung ciliated cell models were used to study the effects of MgATP concentration on ciliary beat frequency and waveform. Models were prepared from ciliated lung cells of the newt Taricha granulosa by trypsin dissociation of the epithelium, demembranation with Triton X-100, and reactivation with MgATP, as described previously [Weaver and Hard, 1985]. Beat frequencies were measured stroboscopically. Ciliary waveforms of reactivated models and intact mucociliary epithelial sheets were determined by single frame analysis of high-speed movies. Waveform parameters calculated included the durations of the effective and recovery strokes, the angular swings and angular velocities of the ciliary base and tip, the position of the bend along the ciliary shaft during the recovery stroke, the velocity of recovery stroke bend propagation, and the ratio of the duration of recovery stroke bend propagation to the duration of the recovery stroke itself. We found that beat frequency varied biphasically in response to MgATP at 21 degrees C, as shown previously for isolated, individual, newt lung axonemes. Apparent Fmax (maximum beat frequency) and Km values of 25 Hz and 0.14 mM, and 35 Hz and 0.47 mM, respectively, were obtained for each linear segment of the biphasic double reciprocal plot. Demembranation did not alter either ciliary waveform or the pattern of coordination. In this system, metachrony is antilaeoplectic and ciliary waveform appears to be regulated independent of beat frequency. PMID- 2933153 TI - Percutaneous transluminal angioplasty of stenotic ductus arteriosus. AB - This article describes our in vitro experience of balloon angioplasty of the ductus arteriosus (DA) in three post mortem human specimens, as well as an in vivo dilatation of a stenotic DA. The in vitro histologic observations revealed disruption of the intima and areas of pathologically fragmented and disorganized fibers at the media, with integrity of the ductal wall in all three DA. These findings led us to attempt percutaneous transluminal angioplasty (PTA) of a stenotic DA in a 2.3-kg newborn infant with hypoplastic left heart syndrome in a very deteriorated clinical condition. A Rashkind septostomy was associated with PTA of the stenotic DA. Following this, the gradients across the DA and across the atrial septum disappeared and the ductal angiographic diameter increased. Although an improved clinical condition was observed during the following hours, he died 1 day after. At necropsy, we found integrity of the ductal wall with histological changes similar to that observed in vitro. We conclude that PTA of stenotic DA could represent an alternative for palliative treatment of DA dependent congenital heart disease. PMID- 2933154 TI - Assessment of dimensions and image quality of coronary contrast catheters from cineangiograms. AB - In the quantitative assessment of coronary arterial dimensions from coronary cineangiograms, the contrast catheter is usually used as a scaling device, requiring the definition of the catheter contours by semi- or fully automated contour detection procedures. The image quality of the x-ray radiated catheter is dependent on the catheter material, concentration of the contrast agent in the catheter, and kilovoltage of the x-ray source. The effects of these variables on the image quality and accuracy of the size-measurement of the filmed catheters were studied for four different catheter materials: woven dacron (wd), polyvinylchloride (pv), polyurethane (pu), and nylon. The following parameters were studied: measured size, image contrast, and average brightness gradient along the edges of the displayed catheters. The average differences of the angiographically measured size with the true size for the wd, pv, pu, and nylon catheters were +0.2, -3.2, -3.5, and +9.8%, respectively. The image contrast at various fillings of the catheters was roughly identical for the wd, pv, and pu catheters, and significantly lower for the nylon catheter. Image gradient was highest for the wd catheter, followed by the pv and pu catheters, and lowest for the nylon catheter. From these data it may be concluded that the woven dacron catheter is most suitable for quantitative coronary angiographic studies. The polyvinylchloride and polyurethane catheters perform about equally well but slightly less than the woven dacron catheter. The nylon catheter should not be used for such quantitative studies. PMID- 2933155 TI - Inhibition of receptor-mediated endocytosis immunoglobulin G by enterocytes isolated from the neonatal rat jejunum. AB - The effect of inhibitors of respiration (NaN3 and DNP), glycolysis (2DG, IAA and NaF) and the microtubular-microfilament system (colchicine and cytochalasin B) on the uptake of rat immunoglobulin G (IgG) by enterocytes isolated from the neonatal rat gut has been assessed. After a 1 hour incubation, NaN3, and DNP had significantly reduced IgG uptake by between 32% and 35% of the control, IAA and 2DG were less effective and NaF, colchicine and cytochalasin B had no effect at all. The findings show that IgG is internalised by isolated enterocytes in vitro and that this internalisation is under metabolic control, that inhibitors of respiration are more effective in blocking uptake than inhibitors of glycolysis. PMID- 2933156 TI - Urinary excretion of 3-methyladenine and 1-methylnicotinamide by rats, following administration of [methyl-14C]methyl methanesulphonate and comparison with administration of [14C]methionine or formate. AB - Following i.p. injection of [methyl-14C]methyl methanesulphonate (MMS) into rats (100 mg/kg) 3-[14C]methyladenine was identified as a urinary product excreted mainly up to 24 h after treatment, the amount over this period being about 0.02 mumol 3-methyladenine. When [14C]MMS and L-[methyl-3H]methionine were injected together no methyl-3H-label was detected in 3-methyladenine, nor was this product detected following injection of [methyl-14C]methionine alone or of [14C]formate. Isotopically labelled 1-methylnicotinamide (1-meNmd) was detected following all the treatments listed, and as previously found by Chu and Lawley, 1-meNmd excretion was enhanced by MMS treatment as judged by increased excretion of 1 [3H]meNmd when [14C]MMS and [3H]methionine were given together. The extent of labelling of 1-meNmd was much lower following injection of [14C] formate, than that from methionine or MMS. The results showed that 3-methyladenine derived only from direct chemical methylation by MMS. They also support the previous suggestion that [methyl-14C]meNmd can result from direct methylation, with a maximal amount of about 3% of excreted meNmd deriving from this route. The possible utility of the methods described for monitoring in vivo alkylation is discussed. PMID- 2933157 TI - [Determination of magnolod and honokiol in different parts of Magnolia officinalis and the effect of processing on their content]. PMID- 2933159 TI - [Research on the originol plant Stellaria dichotoma var. Lanceolata in the ben cao pharmaopeia]. PMID- 2933158 TI - [Comparison on saikosaponin levels in the root of Bupleurum chinense of various sizes]. PMID- 2933160 TI - [Experimental studies on the treatment of acute toxic hepatitis in rabbits with variously processed dan-shen]. PMID- 2933161 TI - [Scientific research to obtain objective data in the processing of Chinese medicinal herbs]. PMID- 2933162 TI - [Chinese medicinal seeds and fruits used as decoctions]. PMID- 2933163 TI - [Preparation and development of the capsules of Chinese traditional drugs]. PMID- 2933164 TI - [Various new chromatographic technics in the separation of constituents of Chinese materia medica]. PMID- 2933165 TI - [Research on the improvement of the preparation of Chinese herbal drugs should be intensified]. PMID- 2933166 TI - [The chemical constituents of Torreyajackii (II)]. PMID- 2933167 TI - [Comparison on the indirubin content of Isatis indigotica at different harvest times]. PMID- 2933168 TI - [Computer analysis of the cold photometric determination of the body surface in rabbits after oral administration of rhubarb]. PMID- 2933169 TI - [Various pharmacological actions of Angelica extracts]. PMID- 2933170 TI - [Effect of different extracts of Rheum palmatum on trypsin activity]. PMID- 2933171 TI - [Experiment on the biological features and cultivation technics of licorice]. PMID- 2933172 TI - [Osteoneogenesis. Preliminary experimental study of the implantation of decalcified bone powder in human surgery]. AB - The allogenic implantation of demineralized bone powder induces the formation of new bone tissue or osteoneogenesis. It is generally admitted that mesenchyme cells differentiate into chondroblasts and osteoblasts. In view of the clinical application of this principle, a series of experiments was performed on the animal. Demineralized bone powder of rat long bones was prepared and implanted in trephine defects of the skull or in the musculus rectus abdominis of young rats. The histologic results are described and illustrated. Very early the implant is invaded by poorly differentiated cells of the mesenchyme type and by blood vessels. It is also surrounded by a thin layer of fibroblasts. At day 10 of the implantation, the formation of cartilage is observed. This cartilage disappears in the following days. At day 20 islets of bone marrow are formed. This tissue is surrounded by osteoblasts in their activation phase. At day 30, these osteoblasts are in a highly active state and produce osteoid, in which osteocytes are enclosed. The osteoid is rapidly calcified. Given the primary localisation of the osteoblasts, the bone marrow lays in the center of newly formed ossicles. Osteoclasts can also be observed. At day 45, the different bone marrow centers tend to fuse laterally and to form larger ossicles. The osteoblasts are in a less active or totally inactive form. Many pieces of the implanted demineralized bone powder are still observable. Inflammatory reactions upon implantation are not observed and the bone tissue formation remains located inside the fibroblast layer surrounding the implant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2933173 TI - [Optic neuropathies]. PMID- 2933174 TI - [Glaucoma]. PMID- 2933175 TI - General anesthesia and surgical stress increase plasma immunoreactive beta endorphin-like substances. AB - The concentrations of human immunoreactive beta-endorphin-like substances in plasma were measured as a means of determining the effects of general anesthesia and surgical stress on the endogenous morphine-like substances. Sixty-nine adult patients and 44 pediatric patients who had undergone oral surgery in general anesthesia were the subjects of this study. In comparison to the control values, the results of this study showed an increase of beta-endorphin concentration in the plasma during anesthesia and surgery. The increase was particularly significant in the patients who had relatively a major surgical stress and in those patients showing a weak anesthetic action, while the patients with relatively a minor surgical stress or strong anesthetic action showed a small increase. From these findings, it seems proper to assume that the secretion of beta-endorphin in the plasma is accelerated by general anesthesia and surgical stress than to assume that the amount of beta-endorphin in the plasma is increased by the administration of anesthetic agents. PMID- 2933176 TI - In vitro responsiveness of ovarian epithelial carcinomas to endocrine therapy. AB - As previously reported, ovarian epithelial carcinomas may respond to endocrine therapy. We examined the direct effect of progesterone, medroxyprogesteroneacetate, gestoneron, 17-beta-estradiol, tamoxifen, 4-OH tamoxifen, or N-desmethyltamoxifen on the proliferative capacity of ovarian carcinoma cells by means of the colony assay described by Hamburger and Salmon. The growth rate of 25 tested tumors (ascitic fluid, primary tumor, metastases) was 68%. The plating efficiency was 0.078%. Beside the drug testing estrogen and progesterone receptor levels were determined. The inhibition of colony survival was slightest with 17-beta-estradiol, more pronounced with medroxyprogesteroneacetate, gestoneron, N-desmethyltamoxifen, and progesterone, and greatest with 4-OH-tamoxifen and tamoxifen. Significant and dose-dependent inhibition of greater than 70% was observed with tamoxifen and 4-OH-tamoxifen in 80% of the tested tumors. There was no significant correlation between the in vitro responsiveness and the level of hormonal act not only via an estrogen receptor but also via an antiestrogen-binding site. PMID- 2933177 TI - Phase II study of 5'-deoxy-5-fluorouridine (doxifluridine) in advanced malignant melanoma. AB - Forty-two patients with malignant melanoma were treated with doxifluridine, 4000 mg/m2 daily X 5, repeated every 3 weeks. The daily dose was reduced to 3000 mg/m2 in patients who had experienced severe myelosuppression with prior chemotherapy. A total of 35 patients were evaluable for response, and 25 of these received two or more courses. Two responses were observed. Toxicity mainly took the form of nausea, vomiting, stomatitis, dizziness, ataxia, and fatigue. Mild leukopenia was frequent (43%). Nadir counts less than 1.5 X 10(9)/l leukocytes or 50 X 10(9)/l platelets were seen in 7% and 2% of the courses respectively. Doxifluridine has no useful activity against malignant melanoma. PMID- 2933178 TI - Altered calcium handling in experimental pressure-overload hypertrophy in the ferret. AB - The purpose of this study was to evaluate the relationship between changes in the intracellular handling of free, ionized calcium and the functional alterations that occur in cardiac hypertrophy. We developed a model of right ventricular pressure-overload hypertrophy in the ferret by critical banding of the pulmonary artery; this method produced significant degrees of hypertrophy within 1-3 months of surgery. We removed papillary muscles, 1 mm or less in diameter, from ferrets with cardiac hypertrophy and their age- and weight-matched controls, and loaded them with the bioluminescent calcium indicator, aequorin, in order to record intracellular calcium transients. Compared to the controls, the hypertrophied muscles demonstrated a prolonged duration of isometric contraction but a marked decrease in peak isometric tension development. The increased duration of isometric contraction in the hypertrophied muscles correlated with a similar prolongation of the calcium transient; we interpret this to mean that the rate of sequestration and perhaps release of calcium by intracellular stores is decreased in hypertrophy. In contrast, the amplitudes of the calcium transients were similar in muscles from both groups of ferrets, indicating that the diminution in peak tension developed by the hypertrophied muscles was not due to decreased availability of activator calcium. We conclude that the prolonged time course of tension development, but not the diminished peak isometric tension response, may be related to changes in intracellular calcium handling. PMID- 2933179 TI - Percutaneous transluminal coronary angioplasty: a surgeon's view. PMID- 2933180 TI - Coronary angioplasty of multiple vessels: short-term outcome and long-term results. AB - Experience with percutaneous transluminal coronary angioplasty (PTCA) of multiple vessels was reviewed to assess short-term outcome and long-term results. PTCA of multiple vessels was performed in 100 of the initial 500 patients (20%) who underwent PTCA at the Medical College of Virginia between July 1979 and August 1984. Eighty-nine percent had class 3 or 4 angina, and 66% had unstable angina. Two-thirds had severe stenosis of two vessels or major branches and one-third had three-vessel disease. One or more significant lesions were dilated in two vessels in 84 patients, in three vessels in 14 patients, and in four vessels in two patients. PTCA of 273 lesions (2.7/patient) was attempted (range two to eight per patient) with angiographic success in 250 lesions (91.6%). Primary success (angiographic and clinical improvement) was achieved in 95 of 100 patients (95%); 84% had success in multiple vessels, and 79% had success in all attempted lesions. Complications occurred in 11 patients (11%); four patients (4%) underwent urgent bypass surgery and four additional patients (4%) had myocardial infarction. Long-term results were assessed in 44 patients with primary success who had follow-up of more than 1 year (mean 26 months) after multiple-vessel PTCA. Twenty-eight patients (64%) remain event-free and improved and 48% are event-free and asymptomatic. Clinical recurrence developed in 15 patients (34%); four had sustained improvement with repeat PTCA, three remain improved with medical therapy, and eight (18%) have undergone bypass surgery during follow-up. One patient (2.3%) developed late myocardial infarction, and deaths have occurred in the follow-up cohort.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2933181 TI - Systemic and transcardiac platelet activity in acute myocardial infarction in man: resistance to prostacyclin. AB - There is increasing evidence that platelets play an important role in the pathogenesis of acute ischemic heart disease. Therefore an understanding of factors that influence platelet performance is important. This study was undertaken (1) to characterize during evolving myocardial infarction platelet activity in the peripheral circulation and across the ischemic/infarcting myocardial compartment, the locus of presumed platelet hyperactivity, and (2) to evaluate the effects of prostacyclin (PGI2), a most potent antiplatelet agent and vasodilator. A total of 59 patients with evolving myocardial infarction were studied. Twenty-two patients were instrumented with arterial and coronary sinus catheters and received intravenous infusion of PGI2, 13 +/- 4.5 ng/kg/min (mean +/- SD), for 90 min. In 15 patients with anterior myocardial infarction, transcardiac platelet function and response to PGI2 were studied. Plasma levels of beta-thromboglobulin (beta-TG) and of thromboxane B2 (TxB2), in vivo measures of platelet activity, were elevated three- and 10-fold. 6-Keto-prostaglandin F 1 alpha, the stable end product of PGI2, was less than 10 pg/ml, reflecting a leftward shift of the TxB2/PGI2 ratio. Platelets circulating during evolving myocardial infarction ("ischemic platelets") were hyperaggregable in response to ADP and relatively resistant to PGI2, both in vivo and in vitro. Concentrations of platelet cyclic AMP and the cyclic AMP response to PGI2 were diminished. The platelet hyperreactivity, expressed by plasma beta-TG, platelet aggregation, and PGI2-induced inhibition of aggregation, was most intense early during infarct evolution and decreased with time. The increased platelet performance resulted in "platelet fatigue," indicated by decreased contents of beta-TG of the ischemic platelet and decreased TxA2 production in response to collagen. However, the ischemic platelet produced twice normal TxA2 in response to arachidonic acid (stimulus and substrate), demonstrating a heightened metabolic capacity. TxA2 was produced across the ischemic/infarcting compartment in 10 of 15 patients with anterior myocardial infarction. The antiplatelet effect of PGI2 was greatly diminished. In summary, the data define an abnormal pattern of platelet behavior during evolving myocardial infarction, characterized by a proaggregatory environment, heightened platelet reactivity in both the peripheral and coronary circulation, and relative resistance to PGI2. The clinical consequences of the data are that the patient in the acute phase of myocardial infarction may benefit from suppression of platelet function and requires significantly greater doses of PGI2 than normal subjects.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2933183 TI - Randomized trials of coronary artery bypass surgery: impact on clinical practice at Duke University Medical Center. AB - Trends in practice patterns at Duke University Medical Center were assessed in patient groups comparable to those enrolled in the three major randomized trials of coronary artery bypass grafting (CABG). In addition, changes in practice patterns that appeared unrelated to the randomized trials were examined. Most patients with 75% or greater left main stenosis have been treated surgically after publication of the Veterans Administration Cooperative Study, but little change was noted in the proportion of patients with 50% left main stenosis who have been treated surgically. A trend towards selection of surgical therapy for patients with three-vessel disease and normal left ventricular function was evident before the publication of the European Coronary Surgery Study, although one-third of patients in this category continue to be treated nonsurgically after publication of the results of the trial. For the past decade, most patients who would have been eligible for the Coronary Artery Surgery Study have been treated nonsurgically. We have also documented trends in practice patterns that are independent of the results of randomized trials. The advent of percutaneous transluminal angioplasty has provided another therapeutic alternative that has been used increasingly. In addition, growing numbers of patients with advanced age, unstable angina, or markedly depressed left ventricular ejection fraction are being evaluated with cardiac catheterization despite the lack of supporting randomized trials. Randomized trials have placed our understanding of the effects of CABG on a sound foundation, but it is evident that clinicians continue to consider many other factors when therapeutic decisions are made. PMID- 2933184 TI - Percutaneous transluminal coronary angioplasty: role in the treatment of coronary artery disease. AB - Percutaneous transluminal coronary angioplasty (PTCA) is indicated for many patients with symptomatic coronary atherosclerosis. It can be safely used in patients with unstable angina pectoris, multivessel coronary disease (in selected instances), multiple stenoses in single vessels, stenoses in coronary artery bypass grafts, and recent total coronary occlusion. PTCA may be useful in reestablishing coronary flow after acute myocardial infarction with coronary occlusion and in association with thrombolytic therapy for acute myocardial infarction. The primary success rate of PTCA in experienced hands should be approximately 90%. If restenosis occurs after successful PTCA, a second procedure can be used to dilate the segment with restenosis and the success rate is high. Acute coronary events are the major complications of PTCA. Less than 5% of patients need emergency coronary surgery. Mortality for PTCA is less than 1%. Complications of PTCA diminish with increasing operator experience. PTCA is not indicated for patients with long-standing complete coronary occlusions, diffuse atherosclerotic coronary stenoses without discrete stenotic segments, multiple sites of total occlusions, or "skip" areas in vessels served by bridging collaterals. Patients with main left coronary stenoses and stenoses involving both sides of large-vessel bifurcations are not considered for PTCA in most centers. The choice for or against PTCA should be made after careful assessment of the risk/benefit ratio of PTCA vs coronary bypass surgery. PMID- 2933182 TI - Determination of left ventricular mass in dogs with rapid-acquisition cardiac computed tomographic scanning. AB - The development of left ventricular hypertrophy in patients with heart disease often has far-reaching clinical implications with respect to overall morbidity and mortality. Approaches used to assess left ventricular mass include electrocardiography, echocardiography, contrast ventriculography, single photon emission tomography, and conventional computed tomography. However, all of these modalities suffer from some major draw back that precludes widespread application to all patients. In this study we assessed the accuracy of determinations of left ventricular mass in 22 dogs by rapid-acquisition (50 msec) computed axial tomography (RACAT), an ultrafast computed tomographic (CT) instrument. Electrocardiographically triggered, end-diastolic, short-axis cardiac scans were obtained from apex to base during administration of intravenous iodinated contrast. Myocardial edges were determined for each tomographic scan by two methods: the regional half-contour method (the CT density half way between that of the left ventricular myocardium and adjacent ventricular cavities or lung) and "interactive plateau thresholding" of the cardiac borders. Left ventricular mass by RACAT was calculated as the sum of the mass of each individual scan from apex to base (modified Simpson's rule). Postmortem left ventricular mass ranged from 58 to 160 g. The correlation between true left ventricular mass and tomographically determined mass was excellent (r = .99), with the slope and y intercept not statistically different from 1 and 0, respectively. The standard error of the estimate was 4.1 g. Interobserver and intraobserver variability for determining left ventricular mass demonstrated excellent agreement (r = .99 and r = .99, respectively). We conclude that quantitative assessment of left ventricular mass can be accurately and reproducibly performed in dogs by rapid acquisition CT scanning. It is likely that this technique will be readily transferable to the clinical settings and prove to be an important method for quantifying left ventricular mass in patients. PMID- 2933185 TI - Indications for transluminal coronary angioplasty. AB - During the 7 years that have followed the introduction of transluminal coronary angioplasty, the indications for this therapeutic, nonoperative procedure have changed from very strict angiographic and clinical criteria to much broader ones. This evolution has occurred because of the technical capabilities of the equipment that is currently available and because of the attractiveness of this nonoperative procedure, which is effective in reducing coronary arterial obstructions. Although there are current studies that demonstrate the effectiveness of the improved techniques for dealing with a larger range of angiographic obstruction, few, if any, clinical studies are currently available that support the widespread use of this technique in patients with clinical syndromes such as new-onset angina, asymptomatic exercise test abnormalities, high-grade stenosis after thrombolysis, etc. As the current indications increase, clinical studies establishing the efficacy of this therapeutic procedure are indicated. PMID- 2933186 TI - Usefulness of coronary artery bypass graft surgery or percutaneous transluminal angioplasty after thrombolytic therapy. AB - Intracoronary streptokinase (STK) was given to 52 patients and 2 million U of intravenous urokinase was given to 15 patients with acute myocardial infarction less than 3 hr from onset of symptoms. Wall motion in the infarct region improved in 20 patients receiving STK alone (-2.5 +/- 1 to 2.1 +/- 1.1 SD/chord) and in 22 patients receiving STK and undergoing coronary bypass surgery within 24 hr (-2.5 +/- 1 to -1.5 +/- 1.0 SD/chord). Wall motion was unchanged in 10 patients not successfully reperfused with STK (-2.9 +/- 0.7 to -3.1 +/- 0.7 SD/chord). Regional wall motion improved at least 1.0 SD/chord in 71% of 14 patients treated within 2 hr of onset of symptoms, but in only 29% of 34 treated after 2 hr. Mean coronary artery stenosis after thrombolysis was 77 +/- 9%. Rethrombosis was associated with a stenotic cross-sectional area of less than 0.4 mm2. Ventricular function did not improve, with a residual stenosis of 0.4 mm or less in diameter. The Western Washington randomized trial reported a 1 year mortality of 2.5% in 80 successfully reperfused patients, but a mortality of 23% in 13 in whom reperfusion was partial and of 14.6% in 41 in whom reperfusion failed. The improved survival with successful reperfusion and improved ventricular performance with early and more complete reperfusion has stimulated interest in the need for angioplasty and coronary artery bypass grafting after thrombolytic therapy. PMID- 2933187 TI - Biosynthesized [35S]methionine-labeled pro-opiomelanocortin peptides as novel recovery markers in radioimmunoassay of peptide hormones. AB - Hormones are extracted from plasma with varying efficiency. Thus, markers or internal standards are often needed, to monitor and correct for extraction losses. To do so is difficult in the case of peptide hormones because radioactive recovery markers either have a low specific activity or, if labeled with iodine, may not be fully representative because of alterations in their size and charge. More importantly, markers labeled with 125I can interact in, and thus compromise, the subsequent radioimmunoassay. AtT-20 mouse pituitary tumor cells, which can be stimulated to synthesize and secrete pro-opiomelanocortin peptides, can biosynthetically label beta-lipotropin (beta-LPH) with [35S]methionine. The labeled peptide, which is co-eluted with unlabeled beta-LPH in "high-performance" liquid chromatography, is fully immunoprecipitable and has a specific activity of 34 Ci/g. We use this labeled peptide to monitor the recovery of beta-LPH in silicic acid extraction from plasma. This peptide is an ideal marker of analytical recovery because it does not interfere in subsequent radioimmunoassays. PMID- 2933188 TI - Enzymatic determination of serum ethanol with membrane-bound dehydrogenase. AB - In this enzymatic method for detecting ethanol in blood by use of membrane-bound microbial alcohol dehydrogenase (no EC no. assigned), the enzyme catalyzes the reaction irreversibly and the rate of oxidation can be monitored by spectrophotometry of the reduction of the indicator dye. No pyridine nucleotides such as NAD+ or NADP+ are used. The calibration curve is linear in the range of 0.1 to 4.0 g of ethanol per liter. Assays of 45 samples of serum having ethanol values ranging from 0.4 to 3.2 g/L by the described technique and a gas chromatographic method gave respective means of 1.734 and 1.732 g/L (r = 0.954). PMID- 2933190 TI - Resource utilization for the neurologically impaired patient. A compendium of available sources. PMID- 2933189 TI - Menstrual migraine, old and new. AB - The authors reviewed the connection between sexual hormones and migraine crisis. Besides other exogenous factors, the fall of estradiol blood levels in the late luteal and premenstrual phase seems a causal factor in the origin of menstrual related headache crisis. The behaviour of migraine crisis during the various events of female reproductive life, support this view. The role of PRL, T, FSH and LH was also discussed. On the other hand, menstrual migraine represents a model that fits perfectly with a neuroendocrine hypothesis which is based upon a faulty chronobiological response of the so-called antinociceptive system. PMID- 2933191 TI - Rehabilitation of the communicatively impaired. PMID- 2933192 TI - Clinical evaluation of sufentanil/pancuronium versus halothane/pancuronium in patients undergoing coronary artery surgery. PMID- 2933193 TI - Hemodynamic effects of sufentanil/metocurine versus sufentanil/pancuronium in patients undergoing coronary artery surgery. PMID- 2933194 TI - Plasma concentrations of sex hormones in postmenopausal women in non-alcoholic cirrhosis. AB - Sex hormone and sex hormone binding globulin (SHBG) levels were measured in the plasma of postmenopausal women with non-alcoholic liver cirrhosis (n = 24) and compared with levels in matched controls (n = 21). Plasma oestradiol was elevated: 80 vs 30 pmol/l, P less than 0.005 (median values). Plasma SHBG was elevated, 15 vs 10 mg/dl, P less than 0.001. Plasma dehydroepiandrosterone sulphate levels were low, 0.35 vs 2.0 mumol/l, P less than 0.0005, as were plasma androstenedione levels, 2.5 vs 4.5 nmol/l, P less than 0.05. There was no significant difference in plasma testosterone. These data suggest that liver disease per se alters sex hormone and sex hormone binding globulin levels in postmenopausal women. PMID- 2933195 TI - A psychometric study of children at-risk for Huntington disease. AB - Huntington disease (HD) is an autosomal dominant disorder of the central nervous system with an average age of onset between 35 and 45 years and symptoms progressing slowly over the next 10 to 20 years. Research in the past few years has focused on the hypothesis that a presymptomatic or prodromal phase for HD is detectable at least 10 years prior to chronic symptoms. This study attempts to identify possible signs of a prodromal phase for HD in children who are at primary (50%) and secondary (25%) risk for HD using a screening battery of psychometric tests. The children tested were between the ages of 5 1/2 and 15 years and the tests used were the WISC-R, the PPVT-R, and the VMI. Results from this study indicated performance on the WISC-R Digit Span and to a lesser extent Coding subtests might be useful in assessing a possible memory dysfunction in children at-risk for HD. PMID- 2933196 TI - Vaccination with a purified blood-stage malaria antigen in mice: correlation of protection with T cell mediated immunity. AB - A purified 230,000 mol wt protein antigen from the lethal mouse malaria parasite Plasmodium yoelii YM which had previously been shown to be highly effective as a vaccine, was tested for its ability to stimulate specific helper T cells and T cells responsible for delayed hypersensitivity. Strong stimulation was found in both assays, but larger doses were required for delayed hypersensitivity, correlating well with the requirements for protection. It is suggested that T stimulation may be a requirement for effective protection by purified antigens in malaria. PMID- 2933197 TI - Suppression of IgE synthesis in vitro by allogeneic T cells from atopic and non atopic subjects. AB - The role of T cells in the regulation of IgE synthesis by human PBMC was studied. PBMC or separated and recombined populations of T and B cells from both normal and atopic donors were cultured for 10 days with and without cycloheximide. IgE and IgG synthesis were determined by specific RIA. IgE synthesis was detected in 0/30 non-atopic, 6/34 mildly atopic and 25/31 severely atopic subjects. Autologous T cells from 10/26 atopic donors, whose B cells synthesised IgE, significantly suppressed this IgE synthesis. The addition of allogeneic T cells from atopic or non-atopic subjects to atopic B cells resulted in greater suppression of IgE synthesis than the addition of autologous T cells. These data support the notion that atopic subjects have naturally occurring IgE isotype specific suppressor T cells as well as suppressor T cells which can be activated during incubation with alloantigen. PMID- 2933198 TI - Percutaneous transluminal coronary angioplasty--effect of the moveable guide wire on the complication rate. AB - Beginning with the first percutaneous transluminal coronary angioplasty (PTCA) performed at Baystate Medical Center, 152 consecutive procedures were analyzed. Sixty were done using USCI-G (nonsteerable) series catheters. In two patients both a G and S (steerable) catheter were used. In 90 procedures the S system was used exclusively. Among the attempted angioplasties with the G series catheter, the percutaneous transluminal coronary angioplasty was successful in 47 (78%). Eight coronary occlusions were induced and all these patients underwent coronary bypass surgery. There were no deaths, but three patients (5%) had acute myocardial infarctions (MI). The two patients in whom both G and S catheters were used had occlusions. One went to surgery and died postoperatively of uncontrollable ventricular arrhythmias. The other patient had a myocardial infarction and recovered. Of the 90 attempts with the exclusive use of the steerable system, 75 were successful (83%). Three coronary occlusions were induced in the 90 attempts and two of the patients had coronary artery bypass surgery. None of the three sustained a myocardial infarction. In summary, the proportion of patients requiring emergency surgery was significantly reduced from 13.3% (8 of 60) to 2.2% (2 of 90) (p=0.02), the incidence of myocardial infarction was reduced from 5 to 0%, and there was a slight increase in the siccess rate of the procedure after the introduction of the steerable system. It is concluded that the steerable system increases the safety of PTCA. PMID- 2933199 TI - Balloon pump support of the failing right heart. AB - This report reviews a clinical experience with pulmonary artery counterpulsation with a balloon pump in a patient with pulmonary embolization superimposed upon severe trivalvular rheumatic heart disease. This patient underwent a pulmonary embolectomy and triple-valve replacement requiring a pulmonary artery balloon pump for bypass discontinuation and postbypass hemodynamic support. The field of right heart counterpulsation is briefly reviewed, and the technical details of the implantation and management of the device are elaborated. PMID- 2933200 TI - Paradoxical ventricular septal motion with right ventricular dilatation as a manifestation of pure pressure overload due to pulmonary veno-occlusive disease. AB - Paradoxical interventricular septal motion with right ventricular dilatation has been considered the hallmark of right ventricular volume overload. We report a 43 year-old woman with severe pulmonary hypertension due to pulmonary veno-occlusive disease who exhibited these echocardiographic abnormalities. Right ventricular volume overload was excluded by physical examination, echocardiography with saline contrast study and by cardiac catheterization, angiography, and shunt study. These echocardiographic findings are thus not pathognomonic of right ventricular volume overload and can be seen with pressure overload as well. PMID- 2933202 TI - [Familial juvenile encephalopathy (Binswanger type) with alopecia and lumbago--a syndrome]. PMID- 2933201 TI - Advances in low-back pain. AB - At the present time there is an epidemic of low-back pain in most industrialized countries. The exact origin of pain is unknown, and probably many structures can play a role. The natural history is extremely good. Only 10% suffer disabling back pain for more than six weeks; nearly 60% return to work within one week. The benefits of motion in the healing process of various connective tissues can be applied also for the back pain sufferer; in addition, the nutrition of the intervertebral disc is improved by moderate motion. Biomechanical factors with epidemiologically proven negative effects for the back pain sufferer have been measured and delineated. Thus, guided activation of large muscle groups is a benefit for the structures of the back as well as the body's own pain-reducing enkephalins. Present knowledge includes a detrimental effect of prolonged inactivation, including long-term bed rest and inactivity, which should be avoided. Better treatment methods, particularly in the surgical field, will evolve from technical advances in the diagnostic field. For the majority of the low-back pain patients who do not need surgical treatment, help will come in the next decade from a collaborative effort from politicians, industrial leaders and engineers, physicians, psychologists, and biomechanicians. PMID- 2933203 TI - Accumulation of technetium-99m MDP in distended ureter. A potential error in diagnosing osteoblastic bone activity. PMID- 2933204 TI - Disturbances of androgen secretion and metabolism in polycystic ovary syndrome. AB - No matter how we define PCO, it is a heterogeneous clinical disorder. The common denominators of this and other overlapping clinical syndromes are the findings of chronic anovulation and androgen excess. Frequently, but not always, these events lead to cystic ovarian changes. The hyperandrogenism may be documented by finding elevated blood levels of ovarian or adrenal androgens or both in combination. The manifestation of this hyperandrogenism, however, is determined by separate factors. It is the degree of 5 alpha-reductase activity in tissues that appears to govern the manifestation of androgen excess. This increased metabolism may be reflected by an in vitro assay of skin 5 alpha-reductase activity or serum levels of 3 alpha-diol G. While 30% of patients with PCO may not have hirsutism, their serum androgen levels are similar to other hirsute patients. Hirsute and nonhirsute patients with PCO may be differentiated by their degree of peripheral androgen metabolism, specifically by their serum levels of 3 alpha-diol G. PMID- 2933205 TI - Effect of single doses of cimetidine and ranitidine on the steady-state plasma levels of midazolam. AB - H2-Receptor antagonists may interfere with the pharmacokinetics of concomitantly administered drugs. Our study was designed to investigate whether cimetidine or ranitidine influence the disposition and sedative effect of midazolam. The effect of single oral doses of 800 mg cimetidine, 300 mg ranitidine, or placebo on the steady-state concentrations of midazolam was examined in a randomized crossover study in eight healthy subjects. A midazolam steady-state concentration was achieved by an intravenous bolus (0.05 mg/kg)-infusion (0.025 mg/kg/hr) technique. Plasma concentrations of midazolam, cimetidine, and ranitidine and the pharmacodynamic response to midazolam (choice reaction time, sedation index) were monitored throughout the 10-hour infusion. Cimetidine significantly increased the mean (+/- SD) steady-state plasma concentration of midazolam from 56.7 +/- 7.8 to 71.3 +/- 19.6 ng/ml (P = 0.004). In contrast, the steady-state midazolam concentration after ranitidine dosing (61.8 +/- 6.8 ng/ml) did not differ significantly from that after placebo. No change in choice reaction time or sedation index was detected after cimetidine or ranitidine dosing. Nevertheless, in contrast to ranitidine, the recently advocated once-daily dosing of cimetidine has a potential for hepatic drug interaction that should be considered before its coadministration with drugs that have a narrow therapeutic index. PMID- 2933206 TI - Effect of etodolac in patients with moderate renal impairment compared with normal subjects. AB - Twenty subjects (10 with normal renal function and 10 with moderate renal insufficiency) participated in an 8-day study to assess the effects of acute and chronic etodolac dosing on renal function. Subjects and patients were hospitalized and followed a controlled diet (150 mEq sodium, 60 to 80 mEq potassium) during the study. A 3-day drug-free period was followed by 4 days of etodolac, 200 mg b.i.d. Sodium balance and body weight remained unchanged in both groups. Modest reductions in renal function as measured by clearances of inulin and p-aminohippurate occurred acutely only in the patients with renal impairment. Chronic therapy resulted in no decrements in daily creatinine clearance. In an average effective anti-inflammatory dose, etodolac did not produce a sustained effect on renal function in either normal subjects or patients with moderate renal insufficiency. PMID- 2933207 TI - Deafness and dental health care. PMID- 2933208 TI - Precautions to prevent the spread of hepatitis in the dental office. PMID- 2933209 TI - DNA repair synthesis in the pancreatic islets of streptozotocin-treated mice. AB - We have investigated the ability of the diabetogenic drug streptozotocin (SZ) to induce DNA repair synthesis following DNA lesions in the cells of the islets of Langerhans of mice. Following intravenous injection of SZ, the pancreatic islets were isolated and incubated with tritiated thymidine. The incorporation of the isotope into cells performing DNA repair synthesis was analyzed using quantitative autoradiography. SZ induced an acute hyperglycemia in the mice together with a significant DNA repair synthesis (an increased tritiated thymidine incorporation) in the islet cells. In similar experiments performed with alloxan, the islet cells degenerated rapidly preventing the detection of DNA repair synthesis. The results support the view that SZ acts on the B cell by causing DNA damage followed by DNA repair synthesis. However, the rapid islet cell degeneration observed following alloxan administration suggests that this B cytotoxin has a different primary mechanism of action, from that of SZ. PMID- 2933210 TI - Peripheral angioplasty: emphasising the need for complete visualisation in lower limb angiography. AB - The importance of optimal visualisation by the use of multiple projections in lower limb angiography is stressed. This is particularly relevant to the safe and effective performance of percutaneous angioplasty; illustrative examples are presented. PMID- 2933212 TI - New, conservative, and exceptionally effective treatment for low back pain. PMID- 2933211 TI - Glomerular sialic acid in Heymann nephritis and diacetylbenzidine induced nephropathy in rats. AB - Glomerular sialic acid was chemically measured in rats with experimental proteinuria induced by N,N'-diacetylbenzidine (DAB) or with autoimmune Heymann nephritis. In DAB nephrosis and in Heymann nephritis the relative amount of glomerular protein was increased. In DAB nephrosis the quantity of sialic acid expressed per amount of protein was decreased, but expressed per amount of DNA, which reflects the number of cells, there was no significant change. In Heymann nephritis the amount of sialic acid was not significantly altered when expressed per amount of protein or per amount of DNA. In individual animals, the amount of glomerular sialic acid expressed per amount of protein or per amount of DNA did not correlate with the severity of proteinuria. An increase in the total number of glomerular cells was found only in Heymann nephritis. The results suggest that proteinuria in the reported models is not the result of changes in glomerular sialic acid. PMID- 2933213 TI - Abdominal wall CT: a pictorial essay. AB - Abdominal CT demonstrates clearly the anatomy of the abdominal wall. This radiographic technique may provide valuable information when pathology is suspected in this region or in the adjacent peritoneum. The muscles, subcutaneous tissues and vascular structures of the abdominal wall should be examined thoroughly when reading routine abdominal CT films. This paper reviews abnormalities identified involving the abdominal wall including hernias, masses, vessels, hematomas, abscesses, ascites, neuromuscular diseases and miscellaneous entities. PMID- 2933214 TI - Enantiospecificity in allergic contact dermatitis. A review and new results in Frullania-sensitive patients. AB - Allergic contact dermatitis is essentially enantiospecific: sensitization to one enantiomer generally does not imply elicitation to the mirror-image allergens. Examples from patients allergic to Frullania, and from the literature (usnic acids, 4-methoxydalbergiones, gamma-methyl-alpha-methylene-gamma-butyrolactones, frullanolides) are discussed. PMID- 2933215 TI - Occupational contact dermatitis from nonylphenolpolyglycolether. PMID- 2933216 TI - Contact dermatitis to paraquat. PMID- 2933217 TI - Pellagroid dermatitis from mancozeb with vitiligo. PMID- 2933218 TI - Formulation of a barrier cream against chromate. AB - A topical cosmetic cream has been developed for use on patients occupationally sensitized to chromate. With the components of this preparation, an in vitro study was carried out, which demonstrated the efficiency of each component. An in vivo experiment on 25 volunteer patients proved a failure. The formula was modified to produce a new cream. The in vitro and in vivo experiences showed satisfactory results in 60 volunteer patients, 60% of whom benefitted from using it. PMID- 2933219 TI - Occupational dermatitis in shrimp peelers. AB - A total of 110 female shrimp production workers from 2 factories were invited to participate in an investigation of occupational skin problems. A questionnaire was filled in by 94 workers and 24 (20.2%) claimed skin problems due to working conditions. In 7 (6%), a diagnosis of occupational dermatitis of the hands was made. In 2, there were strongly positive reactions to shrimp. 5 had negative tests but a positive history of occupational provocation. PMID- 2933220 TI - The phototoxic and allergenic potential of EDS liquids. AB - Liquid fuels derived by direct coal liquefaction may be similar in boiling range and chemical composition to coal tar products. In the past, phototoxicity, an occupational skin disorder, has been associated with coal distillation. Consequently, the phototoxic properties of 5 materials representing the full boiling range of liquids derived from the EDS process were characterized utilizing a guinea pig model. Results with low boiling, coal derived liquids (less than 200 degrees C) were not different from unirradiated controls; however, liquids boiling above 200 degrees C induced phototoxic effects. These results suggest that high boiling EDS liquids may possess phototoxic potential. Differences in the phototoxic activities of liquids of similar boiling range may be related to chemical composition. A study of the allergenic potential of the EDS liquids described above was conducted utilizing the guinea pig maximization test. None of the test materials produced positive responses, suggesting that EDS liquids are low in allergenic potential. PMID- 2933221 TI - Occupational dermatitis from soldering flux among workers in the electronics industry. AB - Although numerous occupational irritants and allergens have been known to cause contact dermatitis in the electronics industry, soldering flux is seldom mentioned. Soldering flux used in the electronics industry can cause both irritant and allergic contact dermatitis. Irritant dermatitis is commoner than allergic contact dermatitis. Aminoethylethanolamine, a constituent of some fluxes, is a sensitizer. Dermatitis tends to start over the periungual area and spread to the finger shafts and sometimes the wrists. The use of cotton gloves by workers appeared to aggravate the problem. Prophylactic measures are essential to prevent occupational contact dermatitis in workers handling flux in the electronics industry. PMID- 2933222 TI - Survey of handicapped physicians in practice. PMID- 2933223 TI - Self-sterility, MHC polymorphism, and spontaneous abortion. PMID- 2933225 TI - Immunoregulatory mechanisms in the uterus and survival of the fetus. PMID- 2933224 TI - Immunomodulation of antitumor response by chemotherapy. PMID- 2933226 TI - Local and systemic regulation of maternal antifetal cytotoxicity during murine pregnancy. PMID- 2933227 TI - FcR derived from without the immune system--a potential escape mechanism for cells propagating in a hostile immunological environment. PMID- 2933228 TI - Nuclear cardiology: current indications and clinical usefulness. PMID- 2933229 TI - Leser-Trelat sign associated with Sezary syndrome. AB - The Leser-Trelat sign is a rare but well known cutaneous indicator of internal malignancy, most commonly adenocarcinoma of the stomach. There have been only a few cases associated with lymphoproliferative malignancies. Sezary syndrome is a chronic leukemia/lymphoma characterized by generalized erythroderma and circulating Sezary cells. We describe a rare case of the Leser-Trelat sign associated with the Sezary syndrome. The skin sign was alleviated through combination chemotherapy. PMID- 2933230 TI - [2 years' clinical follow-up after application of the Concise white sealant system]. PMID- 2933231 TI - Family friends. PMID- 2933232 TI - [Back pain in renal osteodystrophy patients in hemodialysis treatment for more than 10 years]. PMID- 2933233 TI - The mucosal blood flow in pelvic pouches in man. A methodologic study of fluorescein flowmetry. AB - Fluorescein flowmetry implies the measurement of capillary blood flow, expressed as an index between the maximum fluorescence after the first circulatory passage of sodium fluorescein (NaF) and the rise time, defined as the time interval between ten and 90 percent of the maximum fluorescence. A mathematic model based on fluorescein flowmetry was deduced to distinguish a mucosal and muscular blood flow in an intact (unopened) intestine during surgery in man. The hypothesis was that if, at a certain point in time, there is a fixed relationship between the seromuscular fluorescence and the mucosal maximum fluorescence, obtained during the first circulatory passage of NaF, and if the rise times were equal, then a mucosal blood flow could be calculated based on the seromuscular fluorescence. The model was tested in intestinal anastomoses on 16 patients. A fixed relationship between the numeric value of the mucosal maximum fluorescence and the seromuscular fluorescence was found. After five minutes, the ratio was 1:1 and the correlation coefficient at its highest (0.97). It was also found that the rise times were practically identical (r = 0.92). The validity of the model was then tested by comparing it with fluorescein flowmetry, and the correlation coefficient was 0.85. The model was therefore accepted and named indirect mucosal fluorescein flowmetry. Indirect mucosal fluorescein flowmetry was applied to measure blood flow in pelvic pouches in 14 patients, and fluorescein flowmetry in the ileoanal anastomoses in eight patients. The mucosal blood flow in the reservoir, compared with the normal intestine, was reduced to 58 percent if the ileocolic artery or distal branches of the mesenteric artery were ligated, and to 88 percent if the vessels were left intact (P less than 0.05). In the ileoanal anastomosis the mucosal blood flow was reduced to 23 percent compared with the normal intestine (P less than 0.01). The results suggest that stretching and compressing the mesentery might be critical for circulation in the ileoanal anastomoses. PMID- 2933235 TI - [Crystals of a nonspecific complex of cro-repressor with DNA]. PMID- 2933234 TI - Immune function in marmosets. Present state of relevant knowledge. PMID- 2933236 TI - [Professional hand eczema and atopy. A clinical prospective study on correlation]. AB - 683 patients with hand eczema were examined for history and clinical signs of atopy. 242 of these patients suffered from occupational eczema. In more than 50% of this latter group we saw at least 3 references to atopy. This rate exactly corresponds to one established in 441 patients without industrial eczema but with predominantly definite atopic eczema. Thus, atopy exists largely in patients with occupational eczema and in fact furthers the incidence of this disease relevant in social medicine. Early diagnosis of atopy resulting in efficient vocational guidance can diminish the number of cases of industrial eczema. PMID- 2933237 TI - Occupational dermatoses in the food industry. AB - The occurrence of skin diseases in employees engaged in the food industry has been investigated by means of an epidemiological cross-sectional study. Of the 1052 workers in a large factory in Turku (Finland), 17% reported a current skin disease. Occupational eczema was diagnosed in 8,5% of the 541 female employees examined in detail. It was twice as common among those handling fish, meat and vegetables or making "instant" food as among those making confectionery. Hand eczema was present in 15% of the 196 workers handling food, in 8,5% of the 259 confectioners and in 6% of the 86 office employees. History of atopic dermatitis could be revealed in 30% and history of asthma or hay fever without dermatitis in 15% of the employees with current hand eczema. PMID- 2933239 TI - [Differences and change in insurance legal concepts in West Germany]. AB - In the course of the past two decades the social security system has undergone various changes, which escaped the notice of many doctors; some new legal developments and the hereby resulting medical evaluations are presented, whose emphasis embraces the following main fields: statutory social insurance, social claim for compensation, legislation for the seriously disabled, private insurance, rehabilitation and assessment of reduced earning capacity. PMID- 2933238 TI - [Occupational dermatomycoses of zoophilic origin in Bulgaria]. AB - The relative proportion of zoophilic dermatomycoses is increased in comparison with Tinea capitis et pedum. The most frequent zoophilic species now is not only T. mentagrophytes, but T. verrucosum as well. Occupational mycoses caused by T. mentagrophytes and T. quinckeanum in vivaria put forward new problems for experimental medicine. The author states his arguments in favour of T. quinckeanum as a separate, specialized species with reduced morphology, forming scutula. T. verrucosum is phylogenetically the most highly differentiated monoreceptive zoophilic on cattle. With its physiological, parasitological and epidemiological characteristics it is primarily the object of veterinary medicine and also of human medicine. The measures for fighting those mycotic infections are described in detail. Because of cattle-farm expansion the combat of cattle trichophytosis presents in itself a tough problem. The number of the infected is thus also increased. Immunisation with the LFT-130 vaccine and therapy with griseofulvin products containing medicinal feed, according to Kielstein, is recommended. PMID- 2933240 TI - [Transfemoral angioplasty in stenosis of the isthmus of aorta]. AB - A 14-year-old patient with severe aortic coarctation was treated by advancing a balloon catheter across the stenosis via the right femoral artery. The 4 cm long balloon, transversal diameter 15 mm, was filled with saline containing contrast media for 10 seconds. The excess pressure in the balloon was 3.5 at. Subsequently the stenosis diameter increased from 3 to 7.3 mm. The systolic pressure gradient decreased from 75 to 35 mm Hg. After the operation the foot-pulse was palpable for the first time. The highly elevated arterial pressure in the upper extremities decreased markedly. Three months after the operation the vessel diameter was 10.2 mm and the pressure gradient only 10 mm Hg. PMID- 2933241 TI - [Suppressor action of the liver in the graft vs. host reaction]. PMID- 2933242 TI - [Changes in the phosphorylase activity of the heart in myocardial hypertrophy]. PMID- 2933243 TI - [Lymphokines and monokines]. PMID- 2933244 TI - [Effect of cyclophosphane on the suppressor activity of spleen cells in mice with transplantable tumors]. AB - The suppressor activity of the splenic cells in the cyclophosphamide (CP)-treated BALB/c mice with transplanted tumours was studied. CP was injected according to three different therapeutic effective schedules. The analysis of non-specific and antigen-specific tumour-associated suppressor activity in the splenic cell adoptive transfer system demonstrated that CP immunomodulating influence depends on the injection schedule. Usage of the most therapeutically effective CP injection schedule ensured a relative safety of the nonspecific tumour-associated suppressor activity and depression of the specific one. PMID- 2933245 TI - Antiobesity effects of etiocholanolones in diabetes (db), viable yellow (Avy), and normal mice. AB - Two metabolites of the adrenal steroid dehydroepiandrosterone (DHEA), 3 alpha hydroxyetiocholanolone and 3 beta-hydroxyetiocholanolone, were found to have antiobesity properties with respect to both prevention of the development of obesity as well as weight reduction after obesity was established. All of the obesity types studied responded to metabolite therapy to a greater or lesser extent. The more natural obesity seen in certain strains of mice with aging responded most rapidly to the feeding of either metabolite. The effective dosage (0.1%) fed in the diet was only one quarter the dosage required for DHEA to produce the same effect in preventing diabetes symptoms in C57BL/Ks diabetic (db) mutant mice. Unlike DHEA, neither metabolite produced any undesirable estrogenic or androgenic side-effects. 3 alpha-hydroxyethiocholanolone and 3 beta hydroxyetiocholanolone, formerly considered only as inert end products of steroid metabolism, have beneficial actions in mice with various diabetes-obesity conditions and may be metabolic effectors in their own right. PMID- 2933246 TI - Estrogen decreases rat hypothalamic proopiomelanocortin messenger ribonucleic acid levels. AB - Ovariectomy and estrogen (E) or E plus progesterone treatment has previously been shown to alter both hypothalamic content and portal plasma levels of beta endorphin. To determine if these changes were accompanied by changes in beta endorphin synthesis, we used a RNA dot blot method to quantify proopiomelanocortin (POMC) mRNA levels in the arcuate nucleus-median eminence region of rats. Animals were bilaterally ovariectomized, implanted with Silastic capsules containing E or oil, and killed 1 or 3 days after implantation. Total nucleic acid was isolated from dissections of the arcuate-median eminence by proteinase-K/sodium dodecyl sulfate/phenol extraction, and POMC mRNA was quantified by dot blot analysis. Although 1 day of E treatment had no effect on hypothalamic POMC mRNA levels, 3 days of E treatment caused a significant reduction of approximately 40% of POMC mRNA levels relative to oil controls in two replicate experiments. These results suggest that the decreases in hypothalamic POMC peptide levels after E administration reported previously may be due to a decrease in POMC peptide biosynthesis resulting from a decrease in hypothalamic POMC mRNA. PMID- 2933247 TI - The Reproductive Effects Assessment Group's report on the mutagenicity of 1,3 butadiene and its reactive metabolites. AB - A major data gap for assessing heritable risk from exposure to 1,3-butadiene is the lack of mammalian mutagenicity data. The data base on the mutagenic potential of 1,3-butadiene is limited to three bacterial studies from the same laboratory. Two of these studies were positive only in the presence of liver S9 mix from chemically pretreated animals. In vitro data suggest that 1,3-butadiene is metabolized to two epoxide intermediates. 3,4-Epoxybutene, one potential reactive metabolite of 1,3-butadiene, is a monofunctional alkylating agent and is a direct acting mutagen in bacteria. In addition, unpublished data suggest that 3,4-epoxy butene induces DNA damage and chromosomal aberrations in mice. Another potential reactive metabolite, 1,2:3,4-diepoxybutane, is a bifunctional alkylating agent and is mutagenic in a wide variety of organisms (bacteria, fungi, and the germ cells of Drosophila). This metabolite also induces DNA damage in mice and in cultured hamster cells, is clastogenic in fungi and cultured rat cells, and produces chromosome damage/breakage in Drosophila germ cells. These data, when combined with evidence that 1,3-butadiene is carcinogenic in rodent gonadal tissues and is associated with gonadal atrophy in mice, constitute suggestive evidence that 1,3-butadiene may be a human germ cell mutagen. However, because the mutagenicity of 1,3-butadiene has been studied only in bacteria, studies in mammalian test systems are needed to further characterize the mutagenic potential of 1,3-butadiene. PMID- 2933248 TI - Are paraplegics handicapped in the execution of a manual task? PMID- 2933249 TI - Visualisation by low-angle shadowing of the leucocyte-common antigen. A major cell surface glycoprotein of lymphocytes. AB - The leucocyte-common antigen (L-CA) from rat thymocytes is a cell surface glycoprotein of 180 000 apparent mol. wt. with an 80-kd cytoplasmic domain. This paper reports the molecular dimensions of the molecule visualised by electron microscopy after low-angle shadowing. The L-CA monomer consists of a globular head region of approximately 12 nm diameter and a short tail approximately 18 nm long. In deoxycholate both monomers and multimers are seen with aggregation occurring at the head groups. When the detergent is removed, larger clusters are formed with tails extending from a central aggregate. A 100-kd tryptic fragment of L-CA that is known to include the extracellular parts of the molecule also exists in monomer and multimer forms and is seen to have a rod-like structure of length 28 nm without evidence of the head group. Altogether the data indicate that the rod-like structure is found outside the cell and that the extra sequence that forms the head is inside. The tryptic fragment is likely to be derived by cleavage after the transmembrane sequence. PMID- 2933250 TI - Heparan sulphate proteoglycans and their polypeptide chains from BHK cells. AB - A simple procedure for partially purifying membrane-associated 35S-labelled proteoglycans from BHK cells is described. The labelled molecules are mainly heparan sulphate glycoproteins, and their average half-lives are approximately 3 h in culture. A new method, which depends on the degradation of heparan sulphate by nitrous acid at low pH, has been devised to determine the size of the polypeptide moiety of this class of molecule. The BHK cell heparan sulphate proteoglycans contain three main polypeptides having mol. wts. of approximately 65, 85 and 120 kd. PMID- 2933252 TI - Mitochondrial translation of subunits of the rotenone-sensitive NADH:ubiquinone reductase in Neurospora crassa. AB - The rotenone sensitive NADH:ubiquinone was isolated from mitochondria of Neurospora crassa as a monodisperse preparation with the apparent mol. wt. in Triton solution of 0.9 X 10(6). The enzyme is composed of at least 22 subunits with apparent mol. wts. in SDS between 70 and 11 kd. Six of the subunits with the mol. wts. 70, 48, 37, 25, 22 and 18 kd were radioactively labelled in the enzyme isolated from cells which had incorporated [35S]methionine in the presence of cycloheximide. These subunits are synthesized in the mitochondria. Eleven subunits were radioactively labelled in the enzyme from cells which had incorporated [35S]methionine in the presence of chloramphenicol. These subunits are synthesized in the cytoplasm. The site of translation of the other subunits could not be established by the pulse-labelling technique. The assignment of the mitochondrially synthesized subunits to unidentified reading frames on the mitochondrial DNA is discussed. PMID- 2933253 TI - The effect of ketanserin on post-anaesthetic vasoconstriction and shivering. AB - Two homogeneous groups of 20 healthy women submitted to elective gynaecological surgery, who presented after anaesthesia with peripheral vasoconstriction and shivering, were included in a randomized, double-blind study. The first group received 10 mg ketanserin, a new pure antagonist of serotoninergic S2 receptors. The second group received 10 ml saline as placebo. Blood pressure, heart rate, pulse wave amplitude, and rectal and cutaneous temperatures were measured before and 5, 15 and 30 min after treatment. Vasoconstriction, shivering and discomfort were classified as intense, moderate or absent at these times. Venous and arterial blood gases were determined before and 15 min after treatment. Blood pressure and heart rate decreased slightly after ketanserin administration and this decrease was statistically significant. Increases in rectal temperature were similar in both groups. Peripheral temperature, measured in the big toe, significantly decreased in the placebo group but did not change after ketanserin. Vasoconstriction, shivering, discomfort and pulse wave amplitude improved significantly following ketanserin. We conclude that ketanserin may be effective in treating this post-operative complication, the possible mechanism being the vasodilatation it causes; a central serotoninergic blockade could also be implied. PMID- 2933251 TI - Selective translation of heat shock mRNA in Drosophila melanogaster depends on sequence information in the leader. AB - One of the effects of a temperature increase above 35 degrees C on Drosophila melanogaster is a rapid switch in selectivity of the translational apparatus. Protein synthesis from normal, but not from heat shock, mRNA is much reduced. Efficient translation at high temperature might be a result of the primary sequence of heat shock genes. Alternatively a mRNA modification mechanism, altered as a consequence of heat shock, might allow for efficient high temperature translation of any mRNA synthesized during a heat shock. The gene for alcohol dehydrogenase (Adh) was fused to the controlling elements of a heat shock protein 70 (hsp70) gene. Authentic Adh mRNA, synthesized from this fusion gene at elevated temperatures was not translated during heat shock. A second Adh fusion gene in which the mRNA synthesized contained the first 95 nucleotides of the Hsp70 non-translated leader sequence gave rise, at high temperature, to mRNA which was translated during the heat shock. Thus, the signal(s) in the mRNAs controlling translation efficiency at heat shock temperatures is encoded within the heat shock genes. PMID- 2933254 TI - The relationship between muscle myosin ATP-ase activity and isometric endurance in untrained male subjects. AB - The influence of variations in muscle fibre composition on isometric endurance capacity was measured in 23 young healthy untrained male volunteers. After determination of the maximum voluntary force of contraction (MVC), subjects sustained to fatigue contractions at forces of 80%, 50% and 20% of MVC with a 5 min rest between each. A needle biopsy was obtained from m. vastus lateralis and used for histochemical determination of fibre composition based on myosin ATP-ase activity, and fibre are a based on succinate dehydrogenase (SDH) activity. Endurance times were 21 +/- 9 s (mean +/- SD) at 80% of MVC, 56 +/- 17 s at 50% of MVC and 203 +/- 89 s at 20% of MVC. A wide range of muscle fibre compositions was observed with Type I fibres accounting for 48.0 +/- 10.5% of the total, corresponding to 45.0 +/- 11.5% of the total muscle area. Muscle fibre composition, whether expressed as the proportions of the different fibre types present, or as the fraction of total muscle cross-sectional area occupied by each fibre type was not correlated with isometric endurance capacity at any of the three forces studied. Endurance time was also unrelated to MVC. In contrast to the results of previous studies where trained subjects were used, or where different muscle groups were compared, these results suggest that isometric endurance is not influenced by muscle fibre composition. PMID- 2933255 TI - Laser-Doppler and plethysmographic skin blood flow during exercise and during acute heat stress in the sauna. AB - Forearm skin blood flow was measured in six male subjects by laser-Doppler flowmetry (LDF) and venous occlusion plethysmography (VOP) during constant-load (125-200 W) upright bicycle exercise in a warm environment (X + SD, ta 34.6 +/- 0.2 degrees C) and during a 15 min sauna bath (ta 69.0 +/- 2.8 degrees C). During the sauna test the LDF values correlated well with the VOP measurements in the initial phase of active cutaneous vasodilation, after which the LDF values almost leveled off in spite of a steady increase in VOP measurements. During the exercise the mean VOP and LDF values rose in parallel with each other to steady state levels. The relationship between the results of the two methods proved to be nonlinear. It was concluded that different parameters were measured by VOP and LDF. The latter measured mainly the integrated velocity of blood flow in the outermost cutaneous tissue, and this velocity seemed to be partly dependent on the level of the arterial inflow (VOP), but also on the prevailing pressure-flow and pressure-volume relations in the cutaneous vascular bed. PMID- 2933257 TI - A study of some immunological variables in twins, discordant for multiple sclerosis. AB - 11 twin pairs, discordant for multiple sclerosis (MS), were studied: 5 were monozygotic, 6 dizygotic. The mixed leukocyte reaction (MLR) with cells from unrelated patients with MS, the natural killer cell (NK) activity, OKT 4/OKT 8 ratio, and monocyte numbers were studied. The impaired MLR seen in some patients with MS was even more pronounced in the healthy twin, irrespective of the zygosity of the twins. A reduced NK activity and a high OKT 4/OKT 8 ratio is seen in the diseased twin compared to the healthy one, more strongly indicated at monozygosity. The significance of genetics, early environment, and disease is discussed. PMID- 2933256 TI - Structure and function of platelet membrane glycoproteins Ib and V. Effects of leukocyte elastase and other proteases on platelets response to von Willebrand factor and thrombin. AB - Treatment of platelets with human leukocyte elastase causes a rapid loss in response to von Willebrand factor and a biphasic loss in response to thrombin, first rapid then more slowly. The rapid phase corresponds to cleavage of a 45-kDa glycopeptide from the extracellular end of membrane glycoprotein GPIb. Longer treatment removes 80-kDa and 90-kDa glycopeptides and a glycopeptide corresponding to the major part of GPV. The 45-kDa and 90-kDa species could be obtained by elastase treatment of glycocalicin, the major proteolytic cleavage product of GPIb. Polyclonal rabbit antibodies against the purified 45-kDa glycopeptide had the same effect on the action of von Willebrand factor and thrombin on platelets as cleavage of GPIb by elastase. These results indicate that both the von Willebrand factor and thrombin binding sites on GPIb are located in the same region on the outside of the molecule. Thrombin activation of platelets involves at least two receptors, one on the 45-kDa glycopeptide, which when occupied causes an increase in the speed of response of the platelets to the cleavage of the second. GPV, a candidate for the second receptor, is a hydrophobic glycoprotein that is cleaved from the platelet membrane by several proteases. Proteases that do not activate platelets but degrade the second receptor remove larger fragments from GPV than do proteases such as thrombin or trypsin which activate platelets. PMID- 2933258 TI - Platelet behavior in patients with TIA: responsiveness to small doses of aspirin. AB - To study platelet role in cerebrovascular disease, beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) plasma levels, indices of in vivo platelet activation, were assayed in a group of patients affected by cerebral ischemic attack (transient ischemic attack; TIA). Determinations were carried out within 1 month from the ischemic event and following short-term (1 month) and long-term (1 year) daily administration of low doses (50 mg) of aspirin (ASA). After the cerebral ischemic event, beta-TG and PF4 plasma levels were elevated. beta-TG and PF4 plasma levels did not decrease after 1 month of treatment with ASA and significantly increased in all the patients after 1 year. Such a trend can perhaps be related to the natural course of the disease and associated with the possible occurrence of collagen-induced platelet activation in cerebrovascular patients. Data suggest that although platelet activation occurs in TIA-affected patients, the high levels of beta-TG and PF4 may not be adequate parameters for evaluation of TIA relapses and ASA efficacy. PMID- 2933259 TI - T lymphocyte populations in multiple sclerosis. AB - In 36 patients representing different clinical stages of multiple sclerosis (MS) (9 patients with acute exacerbations; 21 patients in remission; 5 patients with chronic progressive MS) determinations of T lymphocyte populations using monoclonal antibodies against surface antigens (OKT3 (pan T cells), OKT4 (helper T cells), OKT8 (cytotoxic/suppressor T cells] were performed. Compared to the control group (40 healthy individuals) a clear elevation of the T4/T8 ratio was found in acute exacerbations and to a lesser degree in patients with inactive phases of MS. Patients with chronic progressive disease did not show increased T4/T8 ratios. Serial determination of lymphocyte populations after corticosteroid therapy in 10 selected patients revealed no significant changes which could be attributed to this therapeutic modality. Pathogenetic and clinical implications of the shifts in surface antigen expression of T lymphocyte populations mirroring the clinical course of MS are discussed. PMID- 2933260 TI - Serum beta-N-acetyl hexosaminidase (beta-NAH) as a discriminant between malignant and benign extrahepatic biliary obstruction: comparison with carcinoembryonic antigen (CEA). AB - Fifty-one patients (16 with malignant extrahepatic biliary obstruction, ten with benign extrahepatic biliary obstruction, eight with alcoholic liver disease, five with viral hepatitis and 12 with liver metastases) and 19 adult healthy controls were studied with determinations of beta-N-acetyl hexosaminidase (a lysosomal enzyme which is cleared from the circulation by the Kupffer cells), carcinoembryonic antigen (CEA), serum bilirubin, alkaline-phosphatase and aspartate aminotransferase (AST). Both CEA and beta-NAH were elevated in each disease group. Elevated beta-NAH levels distinguished between benign and malignant extrahepatic biliary obstruction better than CEA levels. Beta-NAH levels for the malignant and the benign groups were 47.6 +/- 14.7 U/l and 23.0 +/ 4.7 U/l (mean +/- S.D.) respectively. The groups differed significantly (P less than 0.001). Plasma CEA levels for both groups were 18.7 +/- 38.9 and 7.2 +/- 3.3 ng/ml (mean +/- S.D.) respectively. Beta-NAH levels for the 19 normal controls were 15.8 +/- 3.5 U/l (mean +/- S.D.). Beta-NAH also was significantly elevated in patients with hepatic metastases (36.9 +/- 20.1 U/l). In 25 cancer patients with metastases other than in the liver beta-NAH levels (18.3 +/- 5.2) were not significantly elevated over the control group. It has potential value as a marker for non-CEA-producing liver metastases. PMID- 2933261 TI - The effect of a 1-deoxynojirimycin derivative on post-prandial blood glucose and insulin levels in healthy black and white volunteers. AB - BAY m1099 (a 1-deoxynojirimycin derivative) is a glucose analogue which is an alpha-glucosidase inhibitor. Its effects on post-prandial blood glucose and insulin levels was compared with a placebo in 12 healthy male volunteers (6 Blacks and 6 Whites). It produced a similar, significant depression of post prandial blood glucose and insulin levels when the groups were assessed separately and when the data were pooled. Although blood insulin levels in Whites were higher than in Blacks, as previously reported, the difference was not statistically significant and did not appear to influence the response to the drug. BAY 1099 produced no objective or subjective untoward effects and appears to warrant further investigation as an adjuvant to dietary control of diabetes mellitus. PMID- 2933262 TI - Direct effect of interleukin 2 on the differentiation of human B cells which have not been preactivated in vitro. AB - Unfractionated as well as small and large human tonsillar B cells were found to differentiate in the presence of recombinant interleukin 2 (IL2) without requiring an in vitro preactivation signal. These cell suspensions did not contain detectable T cells, monocytes or natural killer cells both at the initiation and the termination of cultures, and did not respond to the T cell dependent polyclonal B cell activator pokeweed mitogen. They contained very few Tac antigen-bearing cells (less than 2.5%) at the beginning and at the termination of the cultures in the absence of IL2. In the presence of IL2, only a minimal increase in the number of Tac antigen-bearing cells was noted. The observed differentiation was not due to the effects of contaminating T cells, since cultures purposely contaminated with up to 5% of T cells did not contain greater amounts of IgM, IgG or IgA than cultures without T cells added back. Furthermore, when T cells were present at a ratio of 1 T cell per 9 B cells, the production of IgM was decreased. Taken together, these data support the hypothesis that (a) B cell differentiation in response to IL2 may occur in the absence of in vitro preactivation, and in this case cannot be related to the expression of Tac antigen on the B cell surface; (b) it is not due to helper effects of very low numbers of T cells which might contaminate the B cell suspensions; and (c) it most likely results from a direct effect of IL2 on B cells themselves. The data also point out the fact that, in the presence of IL2, T cells may trigger inhibitory effects on IL2-induced B cell differentiation rather than provide helper signals. PMID- 2933263 TI - Trypanosoma cruzi: modulation of parasite-cell interaction by plasma fibronectin. AB - Treatment of either rat peritoneal macrophages (RPM), cloned 3T3 fibroblasts (3T3FR) or Trypanosoma cruzi trypomastigote culture forms with human plasma fibronectin (huFN) enhanced their association with the untreated counterpart and this related to the concentration of huFN used. When treatment was performed at 4 degrees C, the enhancing effect of huFN on parasite-cell interaction was greater than that observed at 37 degrees C. This observation could be related to the indirect immunofluorescence antibody assay showing that a significant increase of fibronectin staining was observed on the cell and parasite surfaces upon incubation with huFN and that the extent of fibronectin staining was greater at 4 degrees C. Incubation of huFN-treated or nontreated parasites or cells with anti huFN antibodies exerted an inhibitory effect on the parasite-cell association. The region of fibronectin that interacts with the trypomastigote surface is unknown. Inhibition experiments suggested that the domain of fibronectin which interacts with parasite surface receptors would probably be localized close to the NH2-terminal region of the molecule. Taken together, these results suggest that fibronectin may play a role in the binding of parasites to the vertebrate host cell surface. PMID- 2933264 TI - Human T cell recognition of cloned HLA class I gene products expressed on DNA transfectants of mouse mastocytoma P815. AB - Cloned genes for human major histocompatibility complex (MHC) class I antigens were introduced by DNA-mediated gene transfer into a high-efficiency transfection recipient (HTR) cell line previously derived from mouse mastocytoma P815. Cell surface expression of HLA-A3, AW24 and CW3 gene products on P815 transfectants was demonstrated by radioimmune assay and by flow cytometry. The human MHC class I gene products were apparently expressed on P815 transfectants in a form recognized by human cytolytic T lymphocytes (CTL). Human CTL generated in unidirectional mixed lymphocyte culture against AW24+ donor lymphocytes clearly lysed P815-HLA-AW24+ transfectant target cells, but not untransfected P815(HTR) controls. Moreover, P815-HLA transfectants could stimulate in vitro a significant alloreactive human CTL response. Lysis of P815-HLA transfectant target cells by human CTL was inhibited by a monoclonal antibody directed against human MHC class I gene products. These mouse cell transfectants may be useful for the study of human T cell responses. PMID- 2933265 TI - Search for class II major histocompatibility complex molecular involvement in the response of Lyt-2+ cytotoxic T lymphocyte precursors to alloantigen. AB - A possible requirement for class II major histocompatibility complex (Ia) molecules in the initial activation of cytotoxic T lymphocyte precursors (CTLp) for allocytotoxic responses was investigated. To avoid possible interaction with other alloreactive cell types, a highly purified population of Lyt-2+ splenocytes was used as a source of CTLp. In the light of preliminary results indicating that Lyt-2+ CTLp, even in the presence of interleukin 2 (IL2), could best be triggered into mature CTL in vitro by cells known to be Ia+, we examined whether an interaction of CTLp with Ia antigens (either on syngeneic accessory cells or on allogeneic stimulators) played a role in the development of allocytotoxicity. Results from experiments done with C57BL/6 Lyt-2+ splenocytes co-cultured with P815 stimulator cells and IL 2 showed that the early activation of CTLp was independent of Ia+ syngeneic accessory cells: (a) flow microfluorometry analysis of the responder population at the beginning or after 1 or 3 days of co-culture did not reveal the presence of Ia+ cells; (b) procedures for removal of residual Ia+ cells or of dendritic cells from the responder population before co-culture did not affect the development of cytotoxicity; (c) co-culture with monoclonal antibodies against syngeneic Iab antigens did not inhibit the CTLp activation. By comparing an Ia+ P815 tumor line with its Ia- clone as allogeneic stimulator cells, it was found that the CTLp activation was also independent of Ia alloantigen on the stimulator cells. The response against both the Ia+ and the Ia stimulator cell types was not inhibited by monoclonal anti-L3T4 present in the co-culture, indicating that these responses were not affected by residual L3T4 helper cells. PMID- 2933266 TI - Biochemical and functional characteristics of the human leukocyte membrane antigen family LFA-1, Mo-1 and p150,95. AB - The human leukocyte function-associated (LFA-1) antigen, the monocyte differentiation antigen Mo-1 which is characterized as the C3bi receptor and the glycoprotein p150,95 are characterized biochemically. Immunoprecipitations carried out with 6 different monoclonal antibodies (mAb) against LFA-1 indicated that four mAb (SPV-L1, SPV-L5, SPV-L7 and SPV-L11) were directed against the alpha chain, whereas mAb CLB54 and MHM-23 were found to react with the common beta chain of LFA-1, Mo-1 and p150,95. LFA-1 and Mo-1 expressed on KG-1 cells or lymphocytes, monocytes and granulocytes from one donor were homogeneous. Interestingly the alpha chain of p150,95 showed heterogeneity. The molecular weight of the alpha chain expressed on monocytes was consistently higher than that of the alpha chain on granulocytes. The beta subunits of LFA-1 and Mo-1 (as detected by mAb Bear-1) are not only similar in molecular weight and isoelectric focusing patterns, but it is demonstrated here that they are also identically glycosylated and have similar protein backbones as judged by tryptic peptide mapping. In spite of their structural similarities. LFA-1 and Mo-1 differ completely in some of their biological functions. Anti-LFA-1 mAb strongly inhibited monocyte-dependent T cell proliferation induced by tetanus toxoid or Helix pomatia hemocyanin and pokeweed mitogen-driven specific antibody production in vitro, whereas the anti-Mo-1 antibody Bear-1 was ineffective. These results suggest that the differences in these biological functions of LFA-1 and Mo-1 may be related to their different alpha subunits, which may recognize specific counter structures. PMID- 2933267 TI - Hemodynamic effects of synthetic atrial natriuretic factor (ANF) in dogs with acute left ventricular failure. AB - The hemodynamic and renal electrolyte/function effects of a synthetic peptide (ANF) corresponding to the sequence of the 26 amino acids contained in atrial natriuretic factor (ANF) were assessed in closed-chest dogs in which acute left ventricular failure was produced by coronary artery embolization with 50 micron plastic microspheres. Coronary embolization produced a sustained reduction in cardiac contractility (LV dP/dtmax) and cardiac output which averaged 42 and 44%, respectively. Following a 45 min equilibration period after heart failure induction, most of the hemodynamic functions stabilized. At this time, ANF infused intravenously at 100 pmol/kg per min X 30 min (n = 9) did not lower mean arterial pressure although it increased cardiac output (P less than 0.05) by 17% at only one time period. With the exception of a fall in coronary resistance and an increase in myocardial blood flow, a higher dose of ANF (200 pmol/kg per min) did not consistently alter hemodynamic function. Fractional excretion of sodium (FE Na%) increased 3.4-fold with ANF at 100 pmol/kg per min and 1.8-fold with the 200 pmol/kg per min dose. Neither dose of ANF produced significant effects on renal blood flow (RBF) or glomerular filtration rate (GFR). Plasma angiotensin II which was 91 +/- 20 fmol/ml at baseline increased to 175 +/- 25 fmol/ml (P less than 0.05) 45 min after heart failure induction. However, neither dose of ANF significantly reduced these high circulating angiotensin II levels. These results demonstrate that an infusion of a synthetic ANF stimulated saluresis without altering RBF or GFR, and improved cardiac output in dogs with acute left ventricular failure. PMID- 2933268 TI - Cardiosuppressive effect of alpha-human atrial natriuretic polypeptide (alpha hANP) in spontaneously hypertensive rats. AB - The hemodynamic effects of alpha-hANP were investigated in anesthetized WKY and SHR. Intravenous administration of alpha-hANP (30 ng/min per 100 g bw) caused a marked and rapid reduction in mean blood pressure (MBP) and cardiac index (CI) without any change in the total peripheral resistance index in both strains of rat. The reduction in MBP and CI was significantly greater in SHR than in WKY. It is suggested that SHR may have an enhanced cardiovascular response to alpha-hANP, but the detailed mechanism of such a response is not known. PMID- 2933269 TI - Co-precipitation of intestinal p36 with a 73-K protein and a high molecular weight factor. AB - p36 is a major substrate of tyrosine kinases that co-localizes with spectrin in nonerythroid cells. Recent studies by Gerke & Weber [14] have shown that p36 can be isolated from intestine by selective extraction with the Ca2+-chelating agent EGTA. We now show that p36 can be re-precipitated by adding free Ca2+ to 1 mM with the co-precipitation of a high molecular weight (MW) factor and a polypeptide of 73K. The 73K protein was purified to apparent homogeneity, rabbit antibodies were raised to it and used in Western blots and immunofluorescence microscopy. The 73K protein is found in a wide range of tissues and is particularly concentrated in fibroblasts, where its distribution partially overlaps that of non-erythroid spectrin. PMID- 2933270 TI - Collagen metabolism in the retina of normal and diabetic rats. AB - Glucosyltransferase, an enzyme involved in the synthesis of the carbohydrate portion of basement membranes and collagens, and collagen content were determined in the retina of normal and streptozotocin diabetic rats. No significant difference in glucosyltransferase activity was found at 4 weeks of diabetes. However, the enzyme activity was significantly increased in diabetic rats 12 and 48 weeks following the induction of diabetes. Similarly, a significant increase in collagen content was observed in diabetic retinas after 12 weeks of diabetes. Electron microscopy showed marked thickening of the retinal capillary basement membrane in long-term diabetic (48 weeks) rats. The data suggest that enhanced collagen synthesis and deposition occurs in the retina of diabetic rats, and with duration of diabetes this may result in thickening of the capillary basement membrane. These results are compatible with previously reported increases in kidney glucosyltransferase, collagen synthesis and thickening of the capillary basement membrane in diabetic rats. PMID- 2933271 TI - Busulfan-induced suppression of natural killer cell activity. AB - The effect of repeated injections of busulfan, an alkylating agent, on immune response of CAF1 mice was studied. A single injection of busulfan or acetone (vehicle to solubilize busulfan) acutely suppressed mitogenic and allogenic responses that normalized at two weeks. Repeated injections of busulfan (four injections), on the other hand, showed a transient suppression of the mitogenic responses. Natural killer (NK) activity during the first ten days after busulfan or acetone injections remained normal. NK activity diminished significantly after two injections of busulfan, remained low after four injections, and did not recover within four months of rest. Prolonged suppression of NK activity may be implicated as playing a role in the emergence of T-cell lymphomas in mice injected with busulfan. PMID- 2933272 TI - Audiogenic seizures and brain serotonin after L-tryptophan and p chlorophenylalanine. AB - Despite intense investigation, the role of serotonergic neurons in audiogenic seizures in mice remains uncertain. In the work reported here, audiogenic seizure susceptibility and brain tryptophan and serotonin concentrations were measured in DBA/2J mice after administration of three doses of L-tryptophan or p chlorophenylalanine. p-Chlorophenylalanine reduced brain serotonin and significantly prolonged the latency to appearance of all seizure phases. L tryptophan was largely ineffective in protecting against seizures and in elevating brain serotonin content, despite the fact that it caused a marked increase in brain tryptophan content. Thus, it appears that DBA/2J mice have an impaired ability to synthesize serotonin from tryptophan. PMID- 2933273 TI - Induction of a 70,000 dalton protein in hypertrophic rat heart. AB - Two-dimensional gel electrophoresis analysis of the product of in vitro translation of polyadenylated RNAs extracted from rat heart rendered hypertrophic by aortic constriction, shows a new protein species not present in the map of control hearts. The same is also obtained when hypertrophy is induced by treatment with thyroxine. PMID- 2933274 TI - Modification of acyl-plasmin-streptokinase complex with polyethylene glycol. Reduction of sensitivity to neutralizing antibody. AB - Acyl-plasmin-streptokinase complex has advantages as a 'site' directed fibrinolytic agent with the active site protected from the plasma protease inhibitors. But, in clinical use, the fibrinolytic potential of this acyl-enzyme complex is modified or abolished by the presence of streptokinase antibodies in the patients. Therefore, better therapeutic agents are required. In this work, chemical modification of the acyl-plasmin-streptokinase complex with polyethylene glycol was found to result in marked resistance to neutralization with streptokinase antibodies. PMID- 2933275 TI - Membrane lectins on human monocytes. Maturation-dependent modulation of 6 phosphomannose and mannose receptors. AB - Freshly isolated human monocytes, which do not contain cell-surface mannose specific receptors, bind mannose 6-phosphate and actively endocytose mannose 6 phosphate-bearing neoglycoproteins (6-P-Man-F-BSA). Three days after isolation, human monocytes endocytose very actively 6-P-Man-F-BSA as well as Man-F-BSA, and the endocytosed neoglycoproteins are rapidly degraded. These results were obtained in quantitative flow cytofluorometry by using a panel of fluoresceinylated sugar-substituted serum albumins (neoglycoproteins). Thus, in contrast to mannose receptors which appear only after maturation, mannose 6 phosphate receptors are already present on freshly isolated human monocytes. PMID- 2933276 TI - Abdominal wall metastasis following laparoscopy: a case report. AB - Laparoscopy is commonly used for diagnosis and follow up of malignant disease. Metastatic infiltration of the scar is very rare. We report a case which presented as acute inflammation within 8 days of the procedure. PMID- 2933277 TI - [Student morbidity in a medical college]. PMID- 2933278 TI - [The most active health personnel and their role in realizing epidemic control measures on the territory of Kazakhstan during World War II]. PMID- 2933279 TI - A survey of the occurrence of nivalenol, deoxynivalenol and zearalenone in food stuffs and health foods in Japan. AB - By adopting a rapid and sensitive method for simultaneous detection of nivalenol (NIV), deoxynivalenol (vomitoxin, DON) and zearalenone (ZEN), the natural occurrence of these mycotoxins in Japan in retail marked cereal flours, popcorn and health foods (totalling 76 samples) was surveyed. Significant contamination by NIV and DON was observed in commercial wheat and barley flours, and partially milled grains which are consumed as rice ingredients. Of particular interest was the presence of DON in popcorn imported from the United States, and the high level contamination of NIV and ZEN in job's-tears (Hatomugi in Japanese), a widely marketed health food. PMID- 2933280 TI - [Keratosis palmoplantaris diffusa circumscripta (Unna-Thost)]. PMID- 2933281 TI - Comparison of (Ca2+-Mg2+)-ATPase and Ca2+-ATPase in rat cardiac sarcolemma. AB - The calcium dependency of the Ca2+-pump ATPase of rat cardiac sarcolemma was investigated in the presence and absence of EGTA and EDTA in combination with two free Mg2+-ion concentrations. The results showed: that Mg2+-ions are not essential for the turnover of the Ca2+-pump ATPase; that the Ca2+-affinity is regulated by the concentration of the calcium-chelator complex present in the medium; that (Ca2+-Mg2+)-ATPase and Ca2+-ATPase are probably expressions of the same Ca2+-pump ATPase in the plasma membrane of the cell. PMID- 2933282 TI - Phosphatidylserine and calmodulin effects on Ca2+-stimulated ATPase activity of dog brain synaptosomal plasma membranes. AB - Phosphatidylserine (PtdSer)-liposomes when incubated with synaptosomal plasma membranes (SPM) of dog brain, evoked a significant increase (approx 80%) of the Ca2+-stimulated ATPase activity with maximal effect achieved at around 0.7 mumol PtdSer/mg SPM protein. Higher concentrations of PtdSer led to inhibition of the enzyme activity with respect to the maximal percentage of stimulation. Treatment of SPM with EGTA, to minimize the presence of bound cytoplasmic activator calmodulin, resulted in a mixed mechanism of inhibition of the enzyme activity (Vmax was decreased and Km increased) as estimated by Lineweaver-Burk plots. Addition of exogenous calmodulin resulted in an increase of Vmax and in a restoration of Km to control value. Ca2+-stimulated ATPase activity, in EGTA treated SPM, showed the same figure of changes at different concentrations of PtdSer-liposomes as those of the control, but the turning point was now located at higher PtdSer concentrations. The results suggest that Ca2+-stimulated ATPase activity of SPM is modulated by PtdSer and that calmodulin participates in these interactions, probably, by regulating the contact between the enzyme and Ca2+ ions. PMID- 2933283 TI - Phosphorylation of ribosomal and ribosome-associated proteins in isoproterenol induced cardiac hypertrophy. AB - Cardiac hypertrophy in adult rabbits was induced by subcutaneous injection of isoproterenol. The rate of [3H]leucine incorporation into acid insoluble material was increased and the extent of [32P]phosphate incorporation into several ribosomal proteins was altered. Specifically, a ribosomal protein with a molecular weight of 32,000 from the 40S ribosomal subunit showed a five-fold increase in phosphate incorporation in the hypertrophic heart whereas a protein with a molecular weight of 28,000 from the 60S subunit showed a four-fold decrease. Phosphorylation of ribosome-associated proteins, which could be removed from ribosomes with 0.72 M KCl, was also changed in the hypertrophic hearts. Six major phosphoproteins (with molecular weights 62,000, 49,000, 36,000, 30,000, 20,000 and 12,000) were detected in both the normal and the hypertrophic hearts. Phosphorylation of the 62 K and the 49 K protein was increased by two- and three fold, respectively, in the hypertrophic hearts, whereas phosphorylation of the 36 K and the 30 K protein decreased by two-fold. The level of phosphorylation of the 20 K and the 12 K protein was not significantly changed in hypertrophic hearts. PMID- 2933284 TI - Do chronically ill and handicapped children become depressed? PMID- 2933285 TI - Motor control in infants with Down syndrome. PMID- 2933286 TI - Assessment of the diabetogenic drugs alloxan and streptozotocin as models for the study of immune defects in diabetic mice. AB - The efficacy of the diabetogenic drugs streptozotocin and alloxan were evaluated as models for the study of immune defects associated with diabetes. Streptozotocin- or alloxan-treated mice, with a stable hyperglycaemia of 25-33 mmol/l plasma glucose, were severely impaired in their ability to mount antibody forming, mitogenic, or delayed-type hypersensitivity responses in vivo. Treatment of alloxan-diabetic mice with insulin in vivo completely reversed all immune defects, while insulin treatment of streptozotocin-diabetic mice restored immune function to only 70-80% of normal levels. Results obtained by viability measurements and in vitro biological assays of lymphoid function, including proliferation in response to T- and B-cell mitogens, the production of interleukin-2 by T cells, and the production of interleukin-1 by macrophages indicated that direct exposure to alloxan for 48 h (at concentrations less than or equal to 14 mmol/l) had no adverse effects on lymphoid activity, while exposure to streptozotocin was routinely toxic at concentrations greater than or equal to 1 mmol/l. Both alloxan and streptozotocin exhibited strong toxicity in vitro for isolated pancreatic islet cells. Finally, lymphocytes from streptozotocin-diabetic mice, or cells incubated in vitro with streptozotocin, contained numerous chromosomal abnormalities indicative of DNA strand breakage. Such abnormalities were absent in alloxan-diabetic mice and in cells incubated with alloxan in vitro. These results indicate that immune dysfunction associated with streptozotocin is attributable to direct and irreversible impairment of lymphoid cell function and viability. In contrast, immune dysfunction associated with alloxan-diabetes appears to be a consequence of the diabetic state.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2933287 TI - Protective effect of 3-aminobenzamide, an inhibitor of poly (ADP-ribose) synthetase, against streptozotocin-induced diabetes. AB - The addition of 3-aminobenzamide (a potent inhibitor of poly(ADP ribose)synthetase) into the incubation medium, prevents streptozotocin-induced inhibition of glucose-stimulated insulin release from isolated islets [control 142 +/- 14 microU X islet-1 X h-1; streptozotocin (0.5 mg/ml) 31 +/- 8; 3 aminobenzamide (1.0 mg/ml) 96 +/- 11; streptozotocin plus 3-aminobenzamide 122 +/ 19]. In vivo, intraperitoneal 3-aminobenzamide 300 mg/kg body weight prevents the appearance of overt diabetes in streptozotocin-treated rats. These protective effects of 3-aminobenzamide are dose-dependent and are similar to those exerted by nicotinamide. Taking into account that poly ADP-ribosylation is involved in the repair of damaged DNA, the protection exerted by 3-aminobenzamide against the diabetogenic effect of streptozotocin strongly supports the view that this acute effect may be a major consequence of the activation of DNA repair mechanisms in islet cells. PMID- 2933288 TI - Reduced noradrenaline turnover in streptozotocin-induced diabetic rats. AB - To clarify whether activity of the sympathetic nervous system is decreased in streptozotocin-induced diabetic rats, noradrenaline turnover, which is a reliable indicator of sympathetic nervous system activity, was measured in the interscapular brown adipose tissue, heart and pancreas of streptozotocin diabetic rats. Results from studies using inhibition of noradrenaline biosynthesis with alpha-methyl-p-tyrosine demonstrated significant reductions (p less than 0.05 0.001) in sympathetic nervous system activity in the interscapular brown adipose tissue, heart and pancreas of streptozotocin (65 mg/kg) diabetic rats, compared with measurements in streptozotocin (35 mg/kg) diabetic and saline-control rats. The daily injections of neutral protamine Hagedorn insulin to streptozotocin (65 mg/kg) diabetic rats prevented the decrease of noradrenaline turnover in the interscapular brown adipose tissue and heart significantly (p less than 0.02), but this was less marked in pancreas, compared with non-treated streptozotocin (65 mg/kg) diabetic rats. Furthermore reduced noradrenaline turnover was also observed in the control rats which showed comparable changes in body weight to the rats injected with streptozotocin (65 mg/kg). These results suggest that poorly controlled streptozotocin diabetic rats may have reduced sympathetic nervous function, and that insulin therapy might prevent this. PMID- 2933289 TI - Increased permeability to polyethylene glycol 4000 in rabbits with experimental colitis. AB - Little information is available regarding colonic permeability to macromolecules in health or disease states. In vivo permeability of rabbit colon to [14C]polyethylene glycol 4000 (14C-PEG) was examined in the presence of immune complex-mediated experimental colitis and compared with that of partially treated (control) and normal rabbits. Permeability was assessed by urinary 14C-PEG excretion after intrarectal administration of 0.1 mM solution of 14C-PEG (1 ml/kg, 7.5 X 10(6) cpm/ml). Experimental colitis greatly increased colonic permeability (p less than 0.001 in two-way analysis of variance) compared with control and normal groups (2.06% +/- 0.19%, 0.14% +/- 0.04%, and 0.01% +/- 0.004%, respectively, of rectally administered counts). Gel diffusion chromatography showed that absorbed 14C-PEG was excreted into urine unchanged, demonstrating its applicability as an inert, nonmetabolizable macromolecular probe. Urinary clearance after mesenteric vein administration of 14C-PEG was similar in normal animals and animals with colitis, implicating colonic absorption as the source of the group differences. Postmortem histology confirmed the acute colitis lesions in the experimental group. These findings support the hypothesis that nonspecific colonic inflammation is associated with significant alterations of mucosal permeability. PMID- 2933291 TI - [Analysis of the genetic heterogeneity of homozygous beta+- thalassemia in the Azerbaijan SSR]. PMID- 2933292 TI - [Clinical significance of the heterozygote hemoglobin D carrier state]. PMID- 2933290 TI - Hepatitis in children with acquired immune deficiency syndrome. Histopathologic and immunocytologic features. AB - Hepatic morphology and immunocytology were evaluated in 4 children with clinical and immunologic characteristics of the acquired immune deficiency syndrome or acquired immune deficiency syndrome related complex. All 4 children had hepatomegaly and increased serum alanine and aspartate aminotransferase activity. Both lobular and portal changes were noted. Lymphocytic infiltration, piecemeal necrosis, hepatocellular and bile duct damage, sinusoidal cell hyperplasia, and endothelialitis were prominent. Vesicular rosettes in sinusoidal lymphocytes and tubuloreticular structures in sinusoidal endothelial cells were demonstrated by electron microscopy. The lymphocytic infiltrate in both the lobular and portal spaces was characterized by a relative increase of cytotoxic/suppressor (T8) cells. Hepatitis may be a common feature of pediatric acquired immune deficiency syndrome and acquired immune deficiency syndrome-related complex. Although the histopathologic changes are consistent with chronic active hepatitis, the specific pathogenesis remains to be determined. PMID- 2933293 TI - [Occurrence of antigens, genes and haplotypes of A and B loci of the HLA system in the population of Azerbaijan]. PMID- 2933294 TI - [Hemoglobinopathies in Central Asia]. PMID- 2933295 TI - [Organization and methods of improving services for patients with disorders of the blood coagulation system in the Byelorussian S.S.R]. PMID- 2933296 TI - [Alpha-thalassemia in Azerbaijan]. PMID- 2933297 TI - Early sex differences in hormonal potentialities of gonads from quail embryos with a sex-linked pigmentation marker: an in vitro radioimmunoassay study. AB - Quail embryos with a sex-linked eye pigmentation marker allowing sex identification at autopsy provided a biological model for radioimmunoassay of sex steroids in embryonic quail gonads at a very early stage (51/2 and 61/2 days). The purpose was to demonstrate a sex difference in hormonal potentialities of the gonads before any morphological indication of sexual differentiation. Evidence of early steroidogenesis by undifferentiated gonads could be obtained: estrogen synthesis characterized female gonads, while testosterone was produced by the gonads of both sexes. The sex hormonal production was concomitant with, or even preceded, the apparent beginning of sex differentiation of gonads. PMID- 2933299 TI - [Genetic structure of the populations of native inhabitants in the northeastern USSR. V. The Chukot Evens]. AB - The genetic structure of two Chukot Evens subpopulations (314 individuals) for electrophoretic protein systems and taste sensitivity to PTC was studied. 17 of the 39 loci were polymorphic (43.59%). The following systems were completely monomorphic: diaphorase NAD H (Dia); glucose-6-phosphate dehydrogenase (G-6-PD); glutamatoxalate transaminase (GOT); carbonic anhydrase (Ca-1); catalase (Ct), lactate dehydrogenase (loci LDH-A and LDH-B); leucine aminopeptidase (Lap); malate dehydrogenase (MDH); purine nucleoside phosphorylase (PNP); superoxide phosphorylase (PNP); superoxide dismutase (SOD); phosphoglucomutase-2 (PGM2); cholinesterase (locus E1); red cell esterase (4 loci); albumin (Alb); hemoglobin (Hb A and B); ceruloplasmin (Cp); and blood, gren, using the standard method. The following systems were polymorphic: red cell acid phosphatase (AcP); phosphoglucomutase-1 (PGM1); 6-phosphogluconate dehydrogenase (PGD); glutamatepyruvate transaminase (GPT); glyoxalase-1 (GLO-1); esterase (EsD); adenilatkinase (AK); alkaline phosphatase (Pp); cholinesterase (locus E2); haptoglobin (Hp); transferrin (Tf); group-specific component (Gc) and ABO, MN, Lewis, P blood groups and taste sensitivity to PTC. The following allele frequencies for polymorphic loci have been detected: AKI = 0.994; GLO = 1I = 0.082; GPT1 = 0.653; AcPA = 0.400; AcPB = 0.599; AcPC = 0.001; PGDA = 0.944; PGM1(1) = 0.906; EsD1 = 0.897; E2+ = 0.048; HpI = 0.394; GcI = 0,919; Tfc = 0.987; r(O) = 0.669; p(A) = 0.184; q(B) = 0.146; M = 0.711; Le = 0.411; P1+ = 0.521; t = 0.295. The genetic structure of Chukot Evens population is significantly nearer to that of the other ethnic groups of the North-East, in comparison with the genetic structure of Evenks of the Middle Siberia. PMID- 2933298 TI - Recessive mutations from natural populations of Neurospora crassa that are expressed in the sexual diplophase. AB - Wild-collected isolates of Neurospora crassa Shear and Dodge were systematically examined for recessive mutations affecting the sexual phase of the life cycle, which is essentially diploid. Seventy-four of 99 wild-collected isolates from 26 populations in the United States, India and Pakistan carried one or more recessive mutations that reduced fertility significantly when homozygous; mutations affecting spore morphology were also detected. Limited complementation tests indicate that most of the 106 recovered mutations are unique.--The recessive diplophase (= sexual phase) mutations were uncovered by crossing each wild-collected isolate to a marked two-chromosome double-reciprocal translocation strain as "balancer." Surviving progeny receive approximately 60% of their genome from the wild parent, but receive the mating-type allele from the "balancer" parent. These progeny were backcrossed to the wild parent and were also crossed with a standard laboratory strain (fl). Reduced fertility in the backcross vs. normal fertility in the cross with the laboratory standard signals the presence of a recessive mutation in the wild-collected isolate.--Most of the mutants (95 of 106) fall into two major classes: those producing barren perithecia with no or few viable ascospores (51) and those with spore maturation defects (44). Most of the recessive barrens result either from an early block in meiosis of ascus development (25) or from a late disturbance in postmeiotic ascus behavior (18).- These recessive mutations are formally equivalent to recessive lethals in higher eukaryotes and may be important in determining the breeding structure of natural Neurospora populations. PMID- 2933300 TI - Improved in vitro packaging of coliphage lambda DNA: a one-strain system free from endogenous phage. AB - In previous systems for in vitro packaging of lambda DNA, phages are produced from the packaging components as well as from added DNA. We have developed a new genetic strategy for in vitro packaging that bypasses this endogenous phage problem. Our system employs a single bacterial strain whose lambda prophage codes for all of the packaging proteins but is deleted for cos, the packaging origin. Crude extracts of the single lysogen: (i) are virtually free from endogenous phages, (ii) package added lambda DNA efficiently and (iii) are easy to prepare. Using the cos- in vitro packaging system we show that packaging of lambda linear monomers is a second-order reaction, but that packaging from concatemers prepared by annealing or ligation is first order. We conclude that in our cos- system, linear monomers are a poor substrate for in vitro packaging but that packaging from concatemers works well. PMID- 2933301 TI - High-level synthesis of the phage lambda outer-membrane protein from the cloned lom gene. AB - A 2.7-kb KpnI-EcoRI fragment carrying the lom gene of bacteriophage lambda has been cloned into plasmid pPR42 and recloned into the SmaI site of pUC9. Large quantities of Lom were seen in outer-membrane (OM) preparations of strains carrying the latter clone and its derivatives. The reading frame of lom was identified as ORF206a. The protein was not demonstrably associated either covalently or non-covalently with the peptidoglycan layer of the cell envelope. PMID- 2933302 TI - [Comprehensive approach in the work of the Minsk epidemiological health service in realizing health and hygiene and epidemic control measures]. PMID- 2933303 TI - [Work experience of the hygiene section of an epidemiological health laboratory at the Volkhov Front]. PMID- 2933304 TI - [Effectiveness of supplementary vitaminization and ultraviolet irradiation of female workers in a sewing shop]. PMID- 2933305 TI - [Effect of animal husbandry complexes on the environment and incidence of infectious diseases among the population]. PMID- 2933306 TI - [Physical work capacity and physical fitness of rural schoolchildren in the Moscow district]. PMID- 2933307 TI - [Health status and biological maturity of children in the Udmurtsk Autonomic Republic starting school at age 6]. PMID- 2933309 TI - [Nifedipine as a long acting nitrite: a non-conventional approach]. PMID- 2933308 TI - High-dose depot-medroxyprogesterone acetate--effects on the fatty acid composition of serum lecithin and cholesterol ester. AB - Twenty-one women were treated with high doses of depot-medroxyprogesterone acetate (1000 mg/week im) for 6 months as part of the treatment of endometrial carcinoma. The relative fatty acid composition of serum lecithin and cholesterol ester were analyzed. In previous studies low doses of medroxyprogesterone acetate (MPA), in contrast to progestins of the 19-nor-testosterone series, have been shown not to affect the fatty acid composition of serum lecithin and cholesterol ester. However, the high doses of MPA used in this study increased linoleic acid and decreased arachidonic and di-homogammalinolenic acids in serum lecithin. The ability of a steroid to induce this shift has been ascribed to its androgenicity. MPA is considered to have weak, if any, such properties. The findings of this study emphasize the necessity to delineate effects on metabolism of different doses and administrative routes of any particular steroid. PMID- 2933310 TI - Morphologic observations in coronary arteries, aortocoronary saphenous vein bypass grafts and infant aortae following balloon angioplasty procedures. AB - Morphologic observations following balloon angioplasty are summarized from adult patients undergoing coronary or saphenous vein bypass graft angioplasty and from infants undergoing aortic valve stenosis angioplasty. Possible mechanisms of dilation injury and complications of angioplasty balloon bursting are reviewed. PMID- 2933311 TI - Coronary angioplasty 1985: technical and clinical considerations. AB - As the result of progressive improvements in equipment design and operator technique, PTCA has become an increasingly common alternative to surgical revascularization in the patient with coronary artery disease, achieving favorable symptomatic relief with less patient discomfort, disability and expense. As the scope of PTCA broadens to include multivessel disease and acute ischemic syndromes, however, it is important to continually evaluate it against medical therapy and bypass surgery, and thereby define those patient subgroups for whom PTCA is the treatment of choice. PMID- 2933312 TI - Immediate and long-term results of percutaneous transluminal coronary angioplasty. Comparison of the National Heart, Lung and Blood Institute Registry experience with current experience. AB - The immediate and long-term results of percutaneous transluminal coronary angioplasty (PTCA) in 1939 patients with single-vessel coronary disease (SVD) from the National Heart, Lung and Blood Institute Registry on PTCA (early experience) have been compared to recent results in 1551 patients, also with SVD, pooled from three centers in the USA (current experience). The circumflex artery, rarely subjected to PTCA in the past, now constitutes 16% of the total. The success rate has increased from 65 to 92% and, contrary to previous results, all three coronary arteries share at present a similar rate of success. The complications rate has been halved from 8.4 to 4.2%. These differences stem from the present level of operator expertise and the improved instrumentation. On the other hand, the severity of coronary stenosis and its reduction in successfully treated patients, as well as the rate of recurrence after successful PTCA in the current experience, show no difference from the past. The possible reasons for these similarities are only speculative at this time. PMID- 2933313 TI - Coronary angioplasty in patients who undergo multiple vessel angioplasties, and in patients who have multivessel coronary disease. AB - Percutaneous transluminal coronary angioplasty (PTCA) was performed in patients who underwent multiple vessel angioplasties (MVA) and in patients with multivessel coronary disease (MCD). There were 235 MVA patients who underwent 255 procedures during which 600 lesions were dilated. Two lesions were dilated in 75% of cases, and three lesions in 16% of cases. 93% of the lesions were successfully dilated and 91% of the patients were clinically improved. Complications encountered included a 1.6% mortality, a 3.5% incidence of transmural infarction, and a 2.4% emergency surgery rate. Significant complications occurred in 13 patients (4.6%). A clinically apparent restenosis occurred in 51 patients (24%) with a repeat PTCA performed in 25/26 patients (96%), elective surgery in 14 patients, and the remainder were treated medically. 82% of patients remain clinically improved more than one year after a successful PTCA. There were 331 MCD patients who underwent 387 procedures during which 662 lesions were dilated. One lesion was dilated in 47% of cases, two lesions in 39% of cases, three lesions in 9% of cases, and four or more lesions in 5% of cases. 91% of the lesions were successfully dilated, and 90% of the patients were clinically improved. Complications encountered included a 1.6% mortality, a 3.1% incidence of transmural infarction, and a 3.9% emergency surgery rate. Significant complications were encountered in 35 patients (9%). A clinically apparent restenosis occurred in 46 patients (21%) with a repeat PTCA performed in 29/31 patients (94%), elective surgery in nine patients, and the remainder were treated medically. 86% of patients remain clinically improved more than one year after a successful PTCA. PTCA can be performed in carefully selected patients undergoing MVA, and in MCD patients with a good success rate, a low complication rate, and a satisfactory long term benefit. However, a large clinical trial would be most beneficial in establishing PTCA's role in the treatment of extensive coronary disease. PMID- 2933314 TI - Angioplasty in total coronary arterial occlusion. AB - Percutaneous transluminal coronary angioplasty (PTCA) was attempted in 67 patients with total coronary arterial occlusion but without associated acute transmural infarction. No patient received concomitant streptokinase therapy. The duration of occlusion was one week or less in 22 patients, one week to one month in 24 patients, one to three months in 13 patients, and more than three months in eight patients. The occluded vessel was the left anterior descending artery in 38 (57%), the right coronary artery in 22 (33%), and the circumflex coronary artery in seven (10%). A steerable system was used in 29 patients whereas a fixed guide wire system was used in 38. Dilation was successful in 44 patients (66%). When a steerable system was used, PTCA was successful in 76% of the patients, compared with 58% when a nonsteerable system was used. The average size of stenosis after dilation was 32%. In the patients with a recent occlusion (one week or less in duration), PTCA was successful in 82%, which was significantly better than in patients with an older occlusion (greater than 12 weeks), in whom dilation was successful in only 25% (p less than 0.01). In patients with an occlusion of one to three months, PTCA was successful in 65%. During a mean follow-up of 1.6 years in the 44 patients with successful dilation, 37 were asymptomatic without angina, although five had required repeat dilation or coronary bypass surgery. In selected patients with symptomatic coronary artery disease and recent coronary occlusion but without associated myocardial infarction, PTCA alone is an effective means of restoring flow. After successful dilation, the majority of patients remain asymptomatic. PMID- 2933315 TI - Hepatitis B vaccine: low postvaccination immunity in hospital personnel given gluteal injections. AB - Although other investigators have found excellent response rates to the hepatitis B vaccine, we report here an unusually low rate of seroconversion following hepatitis B vaccination in a group of apparently healthy medical center personnel. Only 67% of these individuals developed adequate postvaccination antibodies to HBsAg, in contrast to 85 to 96% in other studies. A significant decrease in seroconversion with increasing age was noted with a 54% seroconversion rate in vaccines over the age of 40; all of whom had received gluteal injections. Employees at another facility had been given deltoid injections from the same vaccine lot and had an overall seroconversion rate of 90%. Subsequently, nonresponders from the first group were revaccinated. Seven of the ten individuals tested developed anti-HBs. We believe the relatively low rate of seroconversion in individuals above the age of 40 may have been related to gluteal injection of the hepatitis B vaccine, and further investigation is warranted. PMID- 2933316 TI - Hepatotoxicity due to allyl alcohol in deermice depends on alcohol dehydrogenase. AB - The role of alcohol dehydrogenase in the hepatic necrosis due to allyl alcohol was studied in two strains of the deermouse, Peromyscus maniculatus. Mice of the alcohol dehydrogenase-negative (AdhN) strain which lack alcohol dehydrogenase activity were resistant to allyl alcohol toxicity. In contrast, dose-dependent necrosis of periportal regions of the liver and increases in plasma levels of lactate dehydrogenase, sorbitol dehydrogenase and SGOT were observed in plasma from alcohol dehydrogenase-positive deermice (AdhF) 24 hr following administration of allyl alcohol (21 to 84 mg per kg). Half-maximal damage to periportal areas was observed with about 52 mg per kg allyl alcohol. Thus, these data demonstrate that metabolism of allyl alcohol to acrolein by alcohol dehydrogenase is obligatory for the hepatotoxicity of allyl alcohol. PMID- 2933317 TI - Immunotopographic assessment of lymphoid and plasma cell malignancies in the bone marrow. AB - To determine the utility of tissue section immunochemistry in the evaluation of bone marrow involved by lymphoid and plasma cell malignancies, snap-frozen, undecalcified bone marrow core and aspirate samples from 23 patients with these disorders were studied with a battery of monoclonal antibodies. With techniques that preserve architecture, difficult diagnostic cases characterized by core but not aspirate involvement, or the reverse, were resolved. By means of an extensive battery of monoclonal antibodies applied to serial sections, complex tumor cell phenotypes were established in all 23 cases. In addition to the identification of straightforward monoclonal surface immunoglobulin expression in small cleaved cell lymphomas (four cases), the battery approach added immunologic certainty in malignancies with unusual or difficult phenotypes: peripheral T-cell lymphomas with idiosyncratic antigen expression, and chronic lymphocytic leukemias and small cell lymphomas with faint surface immunoglobulin expression (four cases). For the chronic lymphocytic leukemias and the small cell lymphomas, the combined IgD+, B2+, B1+, Ia+, Leu-1+ phenotype taken as a whole had greater utility than any isolated marker. The acute lymphocytic leukemias and the myelomas studied demonstrate the wide range of B-cell antigens that must be detected to account for the variety of B-cell neoplasms encountered. Additionally, the previously undescribed phenotypic subset of CALLA+ myelomas, which is of prognostic relevance, was identified. Marrow frozen section immunotyping is a major asset in the evaluation of patients with lymphoma, leukemia, and myeloma when special care is accorded to tissue handling and to treatment of endogenous peroxidase/pseudoperoxidase and interstitial immunoglobulin. PMID- 2933318 TI - Genetic complementation in somatic cell hybrids of four variants of infantile GM2 gangliosidosis. AB - Cell hybridizations between fibroblasts of four variants (B, O, AB, and B1) of infantile GM2 gangliosidosis were performed. Cocultivated as well as hybrid cells were analyzed for their capability to degrade exogenously added [3H]-GM2. Hybridization of variant AB fibroblasts with fibroblasts of variant O, variant B, or variant B1 resulted in an enhanced rate of GM2 hydrolysis, showing intergenic complementation. Similar restoration of GM2 catabolism was observed after hybridization of variant B1 cells with variant O, but not with variant B cells. These results indicate that B1 cells carry a mutation in the gene locus for the alpha-subunit of beta-hexosaminidase. Studies of the processing of immature enzyme in variant B1 cells showed the presence of alpha-precursors and mature alpha-chains, but at a lower level as compared to normal cells. PMID- 2933319 TI - Down syndrome: increased frequency of maternal meiosis I nondisjunction during the transitional stages of the ovulatory seasons. AB - In a month-of-birth study of Down syndrome (DS) individuals, we found--in agreement with a previous collaborative European study (Jongbloet et al. 1982)--a distribution of maternal meiosis I (Mat MI)-DS births, both graphically and statistically differing from that of both total births (P less than 0.05) and from that of the three other (Mat MII + Pat MI + Pat MII)-DS subcategories (P less than 0.001). In four subgroups, namely the DS individuals born in the years 1960-1979 and 1980-1983 and those from mothers less than or equal to 30 years, and greater than or equal to 31 years, analogous results were found. In addition, the Mat MI-DS individuals were shown to have been conceived more frequently during the "strong" change rate periods. i.e. the transitional stages of ovulatory breakthrough and breakdown, and less during the "weak" change rate periods, i.e. the periods of a rather stable ovulatory rate (P less than 0.05). The same results were found in two subgroups of individuals born 1960-1970 (P less than 0.055) and from mothers greater than or equal to 31 years (P less than 0.02). This interdependence estimated by linear regression in the total group (rs = 0.503; P less than 0.055) and in the subgroup greater than or equal to 31 years (rs = 0.556; P less than 0.05), supports the hypothesis that Mat MI nondisjunctions occur more frequently during the transitional stages of the ovulatory seasons, i.e. they are caused by seasonal pre-ovulatory overripeness ovopathy (SPOO). PMID- 2933320 TI - Equipped for the job. PMID- 2933321 TI - Non-coronary balloon angioplasty. PMID- 2933323 TI - Percutaneous transluminal balloon angioplasty of congenital coarctation of aorta. PMID- 2933322 TI - Mitral balloon valvotomy: a new therapeutic modality for the non-surgical management of mitral stenosis. PMID- 2933324 TI - Pulmonary balloon valvuloplasty for the non-surgical management of valvular pulmonary stenosis. PMID- 2933325 TI - Changing pulsed Doppler echocardiographic flow pattern in mitral stenosis following transvenous balloon mitral commissurotomy--a case report. PMID- 2933326 TI - Cooperativity in inhibition of coupled and uncoupled respiration in rat liver and brain mitochondria by imipramine. PMID- 2933327 TI - Monitoring chloromethyl methyl ether in air. PMID- 2933328 TI - [Conservative care of the handicapped in the dental service of the L. Pasteur Hospital, Colmar regional hospital center]. PMID- 2933329 TI - [Current status of hepatitis B prevention]. AB - There is no causal therapy for hepatitis-B. The most essential therapeutic measure taken for this illness is still prophylaxis, since hepatitis-B can be accompanied by very serious complications (e.g. chronic hepatitis, cirrhosis, primary carcinoma of the liver). PMID- 2933330 TI - Selective contracting in California: early effects and policy implications. AB - California is the first state to enable its Medicaid program and private insurance firms to negotiate with providers for prices to be paid for health services. Initial findings from a two-year study sponsored by the National Governors' Association indicate few problems with Medicaid contracting. Hospital contracts are widely dispersed at prices highly favorable to the state, there has been little documented dislocation of patients or physicians into a two-tier system, and there is no evidence of reduction in quality of care. State savings are estimated at $165 million for the first year of the program. Selective contracting in the private sector, by contrast, has moved more slowly than anticipated, owing to a number of unforeseen barriers. PMID- 2933331 TI - Analysis of length-of-stay differences between investor-owned and voluntary hospitals. AB - In contrast to assertions that investor-owned (I-O) hospitals are more efficient than voluntary hospitals, this study finds no significant difference between I-Os and voluntaries where the efficiency measure is length of hospitalization (LOH). The data base used is a national probability sample of hospitals and patients. The analysis accounts for variation in LOH by controlling for hospital characteristics other than ownership, and in particular it utilizes a new case mix index to control for the case-mix portion of heretofore suggested differences. PMID- 2933333 TI - Biased selection in the Federal Employees Health Benefits Program. AB - The existence of biased selection in health insurance markets has long been assumed by economic theorists as well as seen between classes of health plans. In this paper, we use a model of the premium rate that takes into consideration the effects of moral hazard to make empirical estimates of the extent of selection in the Federal Employees Health Benefits Program. We find that biased selection has raised the premium of the Blue Cross Plan high-option coverage by 21% and lowered the premium of the low-option coverage by 29%, both relative to premiums that would have been charged in the absence of selection. PMID- 2933332 TI - A statistical analysis of reasons for East-West differences in hospital use. AB - Although it is well known that West Coast residents spend 40% fewer days per year in the hospital than do East Coast residents, the reasons for this difference are less well understood. In this analysis of data from the 1977 National Health Interview Survey and Area Resource File, we attempted to isolate which share of the East-West difference is due to population factors and which share is due to characteristics of the health care systems. When we compared New York City hospital use with Los Angeles, population factors were slightly more important than health system characteristics. When we compared other Northeast metropolitan areas with Western metropolitan areas, health system factors were more important. In the case of the New York-Los Angeles comparison, we were able to isolate the following health system characteristics, in order of importance, as especially significant: the backlog of patients in acute care hospitals awaiting placement in long-term care facilities, the greater number of hospital beds per capita in New York City than in Los Angeles, and the larger supply of medical specialists and residents in New York City than in Los Angeles. PMID- 2933334 TI - Cost containment policies in long-term care. AB - The rapidly increasing growth of the elderly population in the United States, especially the increasing proportion of the "old old" among the elderly, has thrust long-term care--its evolution, organization, and financing--into the national limelight. In this report of the effectiveness of various policies to contain the costs of long-term care, I focus on the aggregate public costs of providing this care. I also discuss the impact of public policy on access to needed services by the vulnerable population, the quality of these services, and the quality of life of the recipients of long-term care. PMID- 2933335 TI - Recent evidence on case-based systems for setting hospital rates. AB - Medicare's adoption of the Prospective Payment System (PPS) was the culmination of years of research and demonstrations to establish case-based systems for setting hospital rates. This paper examines the procedures and findings of the early programs in New Jersey and Maryland, as well as the Medicare case-based system that was established pursuant to the experience in these two states. This is followed by an examination of the recently established Medicaid case-based systems in Utah, Pennsylvania, Ohio, Michigan, and Washington and the case-based systems established by some Blue Cross and Blue Shield Plans. The strengths and weaknesses of these systems are discussed, and suggestions are made for improving the evaluations of these systems. PMID- 2933336 TI - Admissions monitoring and scheduling to improve work flow in hospitals. AB - As part of a five-year effort to evaluate alternative methods of improving nurse productivity, this study was undertaken to better understand work flow monitoring as a technique for stabilizing staffing patterns and to improve productivity in hospitals. Two admissions scheduling and monitoring systems were studied and compared with an admissions system without an explicit monitoring function in three medical-surgical units of a 641-bed community hospital. The admissions system based on monitoring case mix was found to be more effective than the system based on monitoring census. Both were significantly more effective than the admissions system without an explicit monitoring function. PMID- 2933337 TI - Relation between the hemolytic property and iron metabolism in Escherichia coli. AB - The hemolytic activity of wild-type strains of Escherichia coli was measured by a standardized method in liquid broth. The system also allowed us to investigate the influence of various Fe3+ concentrations in the cultures on the amount of secreted hemolysin. We found that the hemolysin secretion of all strains was clearly reduced after addition of FeCl3. However, the influence of additional iron chelators showed remarkable differences. The hemolytic activity of Hly plasmid-containing strains isolated in Berne significantly increased. Most of the strains with a chromosomal hemolysin determinant showed a similar effect, but to a lesser degree. Contrary to this, Hly plasmid-containing strains isolated in Essex and some strains with chromosomal hemolysin determinant were either not affected or even showed reduced hemolysin secretion after limitation of free iron ions in the broth. Our results suggest that hemolysin secretion in E. coli is related to the bacterial iron metabolism, and hemolysin secretion is differentially regulated among E. coli strains. PMID- 2933338 TI - Purification and characterization of a primer-independent glucosyltransferase from Streptococcus mutans 6715-13 mutant 27. AB - Affinity chromatography on Sephadex G-50 and subsequent ion-exchange chromatography on Trisacryl-M-DEAE were used to purify the glucosyltransferase (GTF) enzymes produced by mutant 27 of Streptococcus mutans 6715-13. Complete separation of three types of GTF, including a primer-independent GTF capable of synthesizing a slightly branched, water-soluble glucan (GTF-S), was obtained. The characteristics of this primer-independent GTF-S were compared with those of the normally occurring primer-dependent GTF-S. The Km for sucrose was easily obtained for each enzyme (10(-2) M), but the Km for dextran could only be determined for the primer-dependent GTF-S (5 X 10(-7) M for clinical dextran of molecular weight 60,000 to 90,000). The primer-independent GTF-S did not respond catalytically to the presence of either clinical dextran or the highly branched, water-soluble glucan produced by primer-dependent GTF-S, although it was capable of binding these polysaccharides at a noncatalytic site and of responding to the low molecular-weight acceptor 1-O-methyl-alpha-D-glucopyranoside. The water-soluble glucan product of primer-independent GTF-S was a superior priming glucan for primer-dependent GTF enzymes as compared with the glucan product of primer dependent GTF-S. The presence of primer-independent GTF-S in reaction mixtures stimulated glucan synthesis by primer-dependent GTF-S and by GTF synthesizing water-insoluble glucan by at least 10-fold, whereas the presence of similar amounts of primer-dependent GTF-S had no effect on synthesis by GTF synthesizing water-insoluble glucan. Primer-independent GTF-S appears to be a potent source of priming glucan for the primer-dependent GTF enzymes. Its possession of a noncatalytic binding site for glucan, the first observed for the GTF of S. mutans, suggests that it may also serve as a glucan receptor on the S. mutans cell surface. PMID- 2933339 TI - Natural emergence of antigen-reactive T cells in lepromatous leprosy patients during erythema nodosum leprosum. AB - Fifteen lepromatous leprosy (LL) patients undergoing erythema nodosum leprosum (ENL) reactions were compared with 13 stable, uncomplicated, anergic individuals of the same leprosy background. ENL patients showed significant antigen-induced leukocyte migration inhibition (migration index = 0.058 +/- 0.01), paralleling the values obtained with a responder tuberculoid leprosy population (migration index = 0.04 +/- 0.004). Both phytohemagglutinin-induced general T-cell proliferation and, more significantly, antigen-induced lymphoproliferation were enhanced during the acute phase of the reaction. Suppressor cell activity, monitored by a costimulant assay, showed enhanced antigen-stimulated suppression of mitogen responses. Interestingly, the improvement in in vitro T-cell responses was not reflected in dermal reactivity, since 48-h delayed-type hypersensitivity responses after intradermal injection of soluble Mycobacterium leprae antigens continued to be poor. After subsidence of reactional lesions, leukocyte migration inhibition, lymphoproliferation, and suppressor cell activity were reduced to the unresponsive state seen in stable LL patients. Significantly, perturbations of T cell reactivity are detectable in ENL reactions, indicating the natural but transient emergence of antigen-induced T cells in LL. PMID- 2933340 TI - In vitro activity, pharmacokinetics, clinical safety and therapeutic efficacy of enoxacin in the treatment of patients with complicated urinary tract infections. AB - Minimal inhibitory concentrations (MIC) of enoxacin, nalidixic acid, pipemidic acid, norfloxacin, ciprofloxacin, ofloxacin and pefloxacin against isolates from 400 urological in-patients with complicated urinary tract infections (UTI) were determined by means of an agar dilution technique (10(4) cfu, multipointer). 28 patients (21 male, seven female) aged 36 to 84 years with complicated UTI due to sensitive bacteria were treated orally with 200 mg enoxacin b.i.d. for six to 14 days. Plasma and urine samples were collected from 19 patients, at intervals prior to and following a 400 mg dose of enoxacin, and enoxacin concentrations were determined by a high pressure liquid chromatography (HPLC) method. The MICs of enoxacin against all but one of the gram-negative isolates cultured from 265 urological patients were between 0.03 and 4 mg/l. The MICs against 134 gram positive isolates were between 0.25 and 16 mg/l except for two strains of streptococci. At a concentration of 4 mg/l (8 mg/l), 90.3% (98%) of the total spectrum of isolates were inhibited by enoxacin. Of the quinolones tested, ciprofloxacin appeared to be the most active compound in vitro and cinoxacin the least active antimicrobial agent. The in vivo activity of enoxacin was comparable to that of norfloxacin, ofloxacin and pefloxacin. Oral administration of 400 mg of enoxacin to elderly patients resulted in peak serum concentrations between 0.7 and 6.3 mg/l (mean 3.6 mg/l) attained between 1.0 and 6.0 h following drug ingestion. The mean urinary recovery of parent drug within 24 h was 31.2% of the administered dose. 25 of 28 patients treated orally with enoxacin could be followed-up for five to 14 days after the end of treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2933341 TI - Tumour-induced suppression of delayed-type hypersensitivity in the mouse: independence of cyclophosphamide-sensitive suppressor cells. AB - Delayed-type hypersensitivity (DTH) responses to sheep red blood cells and ovalbumin were markedly reduced in mice receiving viable Landschutz ascites tumour cells at the time of immunization. Similar inhibitory effects were observed in control immunized animals when cell-free ascitic fluid or tumour bearer serum was administered together with antigen at the challenge site. Normal mouse serum exhibited much less pronounced inhibitory activity over the range of concentrations tested. High-dose cyclophosphamide (Cy) prior to immunization enhanced DTH responses to both antigens in normal mice. However, in animals also given tumour or soluble tumour-associated material, the immunosuppressive effect which had been observed in non-Cy-treated controls was preserved. It is concluded that the observed suppression of DTH is not dependent on Cy-sensitive T suppressor cells or on the presence of immunosuppressive factors during induction of the immune response. PMID- 2933343 TI - Halogen exchanges using crown ethers: synthesis and preliminary biodistribution of 6-[211At]astatomethyl-19-norcholest-5(10)-en-3 beta-ol. PMID- 2933342 TI - Polyclonal B cell activators inhibit contact sensitivity to oxazolone in mice by potentiating the production of anti-hapten antibodies that induce T suppressor lymphocytes acting through the release of soluble factors. AB - Polyclonal B cell activators (PBAs) such as purified protein derivative, lipopolysaccharide, Staphylococcus aureus strain Cowan I (StaCwI), and Pseudomonas aeruginosa inhibit contact sensitivity to oxazolone in mice when given 24 h before sensitization. This suppression, transferable from immunodepressed animals to oxazolone-sensitized recipients with immune serum, has been shown to be due to the early appearance of anti-hapten antibodies. These antibodies elicit T suppressor cells which release soluble factor(s) capable of inhibiting the passive transfer of contact sensitivity. PMID- 2933344 TI - Chromate sensitivity in Singapore. AB - The incidence of chromate sensitivity in a South East Asian country was found to be 3.22%, the female:male ratio being 1:5, with the majority of the allergies being occupational in origin in men and unexplained in women. Cement was the most common cause among the occupational allergies. Housewives and office workers were the most common occupations in those with unexplained allergies. PMID- 2933345 TI - Anti-androgens in treatment of acne vulgaris. AB - Seventy-five women suffering from acne vulgaris classified into three groups according to the grade of the disease. Anti-androgenic tablets cyproterone acetate (CPA), were given in three cycles. The total number of patients whose condition improved was 52% after the first cycle, 55% after the second cycle, and 81.3% after the third cycle. No serious side effects were encountered. CPA is a suitable therapeutic modility for AV in women who use contraceptives. PMID- 2933346 TI - Proliferative iododerma. A possible mechanism. PMID- 2933347 TI - Naloxone improves sleep apnea in obese humans. AB - To test the hypothesis that endogenous opiates play a role in the etiology of the sleep apnea syndrome, we administered naloxone, an opiate antagonist, to ten obese humans with sleep apnea. On two separate nights we measured the frequency and severity of sleep apnea during naloxone infusion vs saline control infusion. The number of oxyhemoglobin desaturation episodes was not significantly lowered but the average maximal oxyhemoglobin desaturation fell significantly (P less than 0.01) with naloxone. The desaturation index (average maximal oxyhemoglobin desaturation times desaturations per hour) fell by 21 percent (P less than 0.05) on the night of naloxone infusion. Nine of the ten patients had a lower desaturation index with naloxone. REM sleep decreased by 80 percent (P less than 0.05) in the subjects in whom it was measured. We conclude that opiate antagonists hold promise in the treatment of sleep apnea and that the endogenous opiate system may be involved in the production of sleep apnea. PMID- 2933348 TI - Regulation of brown adipose tissue thermogenesis by corticosterone in obese fa/fa rats. AB - The defective BAT function of obese Zucker rats has been related primarily to a loss of diet-induced thermogenesis. The normalisation of BAT function by adrenalectomy has been related to the removal of corticosterone. Experiments with propranolol-blockade and on tissue norepinephrine turnover suggest that corticosterone impairs diet-related sympathetic activity but does not alter BAT response to exogenous norepinephrine. The reduction in serum T3 in obese rats is related to the loss of sympathetic activity. PMID- 2933349 TI - Long-term follow-up of chronic pain patients: a preliminary study. AB - Patients who participated in a structured outpatient pain management program were followed for twenty-four to forty-three months with a mean of 31.8 months. Patients who were evaluated only were compared with patients who terminated prematurely or completed treatment. Patients completing treatment reported greater ability to handle domestic and occupational tasks, and greater tolerance for exercise. There appeared to be no significant effect of treatment on the subjective experience of pain, but patients who completed treatment reported markedly reduced use of medical resources for diagnosis and treatment of pain. Limitations of the present study are discussed. PMID- 2933350 TI - Electrolytic reduction of nitroheterocyclic drugs leads to biologically important damage in DNA. AB - The effect of electrolytic reduction of nitroimidazole drugs on biologically active DNA was studied. The results show that reduction of the drugs in the presence of DNA affects inactivation for both double-stranded (RF) and single stranded phi X174 DNA. However, stable reduction products did not make a significant contribution to the lethal damage in DNA. This suggests that probably a short-lived intermediate of reduction of nitro-compounds is responsible for damage to DNA. PMID- 2933351 TI - The place of rehabilitation in geriatric medicine; an overview. AB - Rehabilitation plays an important part in geriatric medicine. It is important to consider this in the current discussions on rehabilitation and disability medicine. The historical development of geriatric medicine and physical medicine shows similarities. Geriatric medicine has developed from a stage in which the main problem was the application of rehabilitation principles to long-stay wards containing large numbers of immobilized elderly patients, to the present, when emergency admission policies, age related policies, and joint geriatric and general medical firms are common. The attitude to rehabilitation has consequently changed from a serial, staged programme, to an holistic approach in parallel. PMID- 2933352 TI - Rehabilitation of the elderly patient--ways and means. AB - This paper first considers in retrospect the start made upon rehabilitation in the 1940s. Some of the basic principles of organizing a district geriatric service with potential to rehabilitate its patients are set out. The need for a holistic, multidisciplinary approach is emphasized. The time for starting, and the first measures to apply, are discussed, together with the personnel required, and the necessity for good liaison between all the professions. The paper then discusses the right location for a geriatric rehabilitation department, the combination of a ward and a day hospital, the type of environment to be aimed at within it, and finally the equipment required. PMID- 2933353 TI - Geriatric rehabilitation in day hospitals. AB - The main objective of geriatric day hospitals, that of physical rehabilitation of elderly patients mainly with strokes and arthritis, is matched by their facilities and their medical, nursing and therapy staffing. Patients attend by ambulance on 1 or 2 days a week for about 3 months for assessment and treatment, while continuing to live at home. Day hospitals are a popular and effective resource for the rehabilitation of selected patients, though not necessarily cheaper than institutional care. Problems remain in the separation of social care and psychogeriatric patients and in ambulance transport. PMID- 2933354 TI - Rehabilitation in Japan. PMID- 2933355 TI - What would occupational therapists do if they had more staff? AB - Eighteen per cent of 203 departments responding to a questionnaire felt they had sufficient staff, and this group had, on average, significantly more therapists than those who felt that they had insufficient staff. Treatment was mainly concentrated on individual therapy though, in some units, excessive time was spent on administration and travelling. Very little therapy time was spent on diversional activities but this was one area, along with treating more patients and increasing pre-discharge home visits, which they would like to develop if more staff were available. Little additional time would be spent in research, teaching or community therapy. PMID- 2933356 TI - Skin microvascular autoregulatory responses in type I diabetes: the influence of duration and control. AB - We have studied skin microvascular autoregulatory responses in healthy control subjects (n = 11) and three subgroups of uncomplicated Type 1 diabetics. Group 1 (n = 10) had a duration of diabetes of less than one year. Group 2 (n = 10) had a mean duration of diabetes of 11 years. Group 3 (n = 9), of similar duration to group 2, were selected on the basis of having HbAl values persistently below 9%. To assess autoregulatory capacity we determined time to peak capillary flow velocity (CBV) in single nailfold capillaries following release of 60 s arterial occlusion by videophotometric capillaroscopy, and the percentage fall in finger skin rest flow measured by laser Doppler flowmetry when 50 mm Hg venous occlusion was applied. Time to peak CBV was prolonged in groups 1 and 2 compared to controls, (controls 7.7 +/- 1.4 s, mean +/- ISD, group 1 10.7 +/- 2.9 s, p less than 0.01; group 2 11.6 +/- 3.0 s, p less than 0.002) but not in group 3 (9.3 +/- 3.0 s, NS). The percentage fall in resting microcirculatory flow in response to venous occlusion was reduced in groups 1 and 2 compared to controls (controls 57 +/- 16%, group 1 40 +/- 19%, p less than 0.05; group 2 22 +/- 16%, p less than 0.002). In group 3 the response was significantly different from the control value (group 33.7 +/- 20%, controls 57 +/- 16%, p less than 0.05). Thus skin microvascular autoregulatory responses are disturbed within the first year of diabetic life and after 10 years disease duration the impairment is more marked.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2933357 TI - The clinical significance of alpha 1-antitrypsin-elastase (alpha 1AT-ELP) and alpha 2-antiplasmin-plasmin (alpha 2AP-PL) complexes for the differentiation of coagulation protein turnover: indications for plasma protein substitution in patients with septicaemia. AB - In inflammation, particularly in septicaemia, complex coagulation disorders may lead to a dangerous haemorrhagic diathesis. The conventional concept for this syndrome called DIC implicates the occurrence of active thrombin in the circulation, which may be followed by hyperfibrinolysis due to plasmin formation. In this study data are presented suggesting an important role for a third proteolytic system, granulocytic elastase. The complexes of plasmin and elastase with their specific inhibitors, alpha 2-antiplasmin-plasmin (alpha 2AP-PI) and alpha 1-antitrypsin-elastase (alpha 1AT-ELP) were determined immunologically. The alpha 1AT-ELP appears mainly in gram-negative septicaemia, particularly in meningococcal disease. The estimation of alpha 2AP-PI and alpha 1AT-ELP, together with a method for the detection of the antithrombin III--thrombin complex which remains to be established, is a suitable tool for for the differential diagnosis of the consumption of coagulation proteins. The assumption that at least three proteolytic systems participate in the development of the haemorrhagic diathesis during inflammation leads to the concept of a broad, comprehensive substitution therapy with e.g. concentrates of AT III, PPSB, or fresh frozen plasma. The aim of this treatment is to replace not only the consumed procoagulatory factors, but also the lacking inhibitors in order to control this "abnormal proteolysis syndrome". PMID- 2933358 TI - [Mechanism of action of cyclosporin A]. PMID- 2933359 TI - Retinal photoreceptor-pigment epithelium interactions. Friedenwald lecture. PMID- 2933360 TI - Synergistic combination of menogarol and melphalan and other two drug combinations. AB - Menogarol is a new anthracycline undergoing phase I clinical trial. We report here the lethality after 2 hr exposure to 2 drug combinations of menogarol and several antitumor agents. A new statistical procedure was used to identify synergistic combinations. Most of these combinations were additive, except for menogarol plus melphalan, which was synergistic. Adriamycin plus melphalan was also synergistic. The menogarol-melphalan combination wa studied in detail with regard to the effect of dose and drug-schedule, lethality for exponential and plateau phase cells and effect on cell cycle progression. Although the combination was synergistic for exponential cells it was additive for plateau phase cells. The combination exerted a synergistic effect in inhibiting progression of cells through the cell cycle. After 2 hr menogarol exposure cells were blocked in G2 for about 12 hr following which the block was reversed. This reversal was inhibited when menogarol was combined with melphalan. The uptake of menogarol or melphalan was not changed in the presence of the other drug. PMID- 2933361 TI - AUR memorial Award. Induced alignment of flowing sickle erythrocytes in a magnetic field. A preliminary report. AB - Deoxygenated sickle erythrocytes in static suspension align perpendicular to a magnetic field. To assess the importance of this observation to MRI of sickle cell disease, an in vitro flow apparatus was devised and the orientation of sickle erythrocytes flowing through a 0.38 T magnetic field was investigated. We showed a significant perpendicular alignment of fully deoxygenated sickle erythrocytes flowing at 3 to 4 mm/minute (P less than .001). These results suggest that deoxygenated erythrocytes in a sickle-cell patient could orient perpendicular to a magnetic field, and therefore that MRI of such patients could possibly result in worsening of vaso-occlusive complications. Further studies are needed to assess the possible hazards of MRI of sickle-cell disease, especially at high field strengths. PMID- 2933362 TI - Pharmacokinetics and excretion of iohexol after lumbar myelography in man. AB - Pharmacokinetics and excretion of iohexol, a new nonionic water-soluble contrast medium, were determined after lumbar myelography. Peak plasma concentrations were obtained 2 to 6 hours after injection and ranged from 29 to 177 microgram/ml. Terminal elimination half-life was 4.0 hours, and over 90% of the dose was recovered in the urine within 24 hours. In one patient with a large lumbar cauda equina tumor, absorption and excretion were delayed; but eventually 99% was recovered indicating a large capacity for reabsorption via the lumbar subarachnoid space. One mild headache of 5 minutes' duration was reported in a 73 year-old woman. No significant changes in vital signs, neurologic examinations, or serum chemistries were observed. PMID- 2933363 TI - Accelerated thrombolysis. In vitro evaluation of agents and methods of administration. AB - Three groups of experiments were conducted in vitro to determine the relative rates of thrombolysis produced by current clinically-relevant concentrations of streptokinase (SK), urokinase (UK), tissue-type plasminogen activator (t-PA), and plasmin; the concentration-response curves for each agent; and the advantages of mechanical admixture of fibrinolytic agents over simple soak. For Group 1 and 2 experiments, thrombolysis was quantitated by weighing freshly prepared clots before and after 2-hour fibrinolytic soaks. For experiments in Group 3, radio labeled fibrinogen clots were used, and the amount of lysis was determined by measuring radioactivity in residual clot and supernatant fluid. Results indicated that SK, UK, plasmin, and t-PA in saline all produced roughly equivalent rates of lysis at molarity of 10(-6). Concentrations of SK above this level (corresponding to above 5000 units/ml) slowed lysis markedly; progressively increasing concentrations of UK and t-PA produced faster lysis, with slope of about 17 and 37%, respectively, per log10 of concentration. The efficacy of fibrinolytic agents was significantly enhanced by admixing clot and agent, using intrathrombic injections or clot maceration. With clot volumes of 0.5 ml, residual clot was frequently only 1/2 to 1/3 as much from macerated clots as from clots that were soaked whole. With the further addition of intrathrombic plasminogen, lysis was nearly completed after 30 minutes. PMID- 2933364 TI - Protection of disabled newborns: are there constitutional limitations? PMID- 2933365 TI - Death by design of handicapped newborns: the family's role & response. PMID- 2933366 TI - Benign congenital hypotonia with uniform type 1 fibers and aspecific ultrastructural changes in the muscle: a case with esophagus involvement. AB - We report the case of a child with congenital neuromuscular disease characterized by neonatal onset of symptoms, a floppy syndrome with marked weakness of facial muscles, palsy of the velum pendulum and hypomotility of the esophagus. EMG was inconclusive. Serum enzyme levels were within the normal range. Muscle biopsy specimen showed uniform type 1 fibers, smallness of the occasionally observed type 2 fibers and slight ultrastructural changes in many fibers. On the basis of the clinical and morphological features we have included the present case among the group of non-progressive congenital neuromuscular diseases. PMID- 2933367 TI - Influence of beta-endorphin on phytohemagglutinin-induced lymphocyte proliferation and on the expression of mononuclear cell surface antigens in vitro. AB - Recent evidence suggests that opiates can modulate the immune responses. In particular it has been shown that beta-endorphin and morphine are able to depress some T lymphocyte functions in humans. In the present study, experiments were designed to evaluate the effect of beta-endorphin phytohemagglutinin-induced lymphocyte proliferation and determine the mechanism of this action. The ability of naloxone to block the effect of beta-endorphin was also investigated, and the influence of beta-endorphin on the expression of mononuclear cell surface antigens using the OKT3, OKT4, OKT8, anti-HLA-DR and anti-beta 2-microglobulin monoclonal antibodies was evaluated. Phytohemagglutinin-induced lymphocyte proliferation was significantly inhibited by beta-endorphin. This effect occurred when beta-endorphin was added to cells at the beginning of the culture period (30 min before, simultaneously or 30 min after phytohemagglutinin), but not when added after 48 h of incubation. The preincubation of cells with BEP for 1 h, 4 h or 24 h did not affect lymphocyte activation by phytohemagglutinin. A ten-fold excess of naloxone, added to cultures 30 min prior to beta-endorphin, did not block the inhibitory effect. Incubation with beta-endorphin had different effects on each surface antigen tested. The OKT8+ and beta 2-microglobulin+ cells did not show significant variations. The OKT4+ cells significantly decreased, after 4 h of incubation with beta-endorphin, both in mononuclear cell and in purified T lymphocyte cultures and, after 24 h, in mononuclear cell cultures only. The OKT3+ cells decreased, in mononuclear cell cultures only, after 24 h beta-endorphin incubation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2933368 TI - Keeping Elizabeth Bouvia alive for the public good. AB - The case of Elizabeth Bouvia, a handicapped woman who wanted doctors to assist her in dying, reveals that autonomy is insufficient as the sole or even the most important public policy principle. Where the community is asked to endorse a course of action by granting medical and financial assistance, considerations of autonomy must give way to the broader notion of the public good, which gives primacy to the respect for life. PMID- 2933369 TI - [Erythema scarlatiniforme desquamativum recidivans localisatum]. AB - Two patients are reported who had the clinical picture of localized erythema scarlatiniforme desquamativum recidivans. The lesions were thought to be drug induced in a 56-year-old female patient. In the other 54-year-old male patient, staphylococcal infections may have caused the rash. PMID- 2933370 TI - [A case of erythrokeratodermia variabilis]. AB - A case of erythrokeratodermia variabilis in a 7.5-years-old girl with transient achromic lesions and nail changes is described. Histologically peculiar eosinophilic formations with nuclear remnants in the stratum corneum were found. The mother and the grandfather only had hyperkeratotic lesions on the soles. PMID- 2933371 TI - [Systemic retinoid therapy with etretinate in pachyonychia congenita]. AB - On the basis of two case-reports it is concluded that the aromatic derivative of retinoic acid, etretinate, is a promising drug in the treatment of pachyonychia congenita. PMID- 2933372 TI - [Treatment of seborrheic dermatitis with low-dosage dithranol]. AB - This report describes the successful treatment of facial seborrheic dermatitis with a low-dose dithranol preparation. The results of a pilot study involving 18 outpatients are presented. PMID- 2933373 TI - Myosin-ATPase fibre typing of chemically skinned muscle fibres. AB - The efficacy of myosin (M)-ATPase fibre typing to differentiate fibre types in chemically (EGTA) skinned muscle fibres was investigated. Cryosections or single fibres from isolated bundles of chemically skinned rat extensor digitorum longus (EDL) and soleus (SOL) muscles were stained for M-ATPase activity. The results indicate that two major fibre types (type I and II, Brooke & Kaiser, 1970) can be identified, as well as subgrouping of the type II fibres into types IIa and IIb. Thus, chemically skinning muscle fibres appears to have no detrimental effects on subsequent M-ATPase fibre typing. PMID- 2933374 TI - Ultrastructural cytochemistry of glycoconjugates in basophils from humans and animals. AB - The distribution of glycoconjugates in the basophil granules of humans, guinea pigs, and rabbits was compared. The observation of acid mucopolysaccharides using the dialyzed iron method and of sulfated glycoconjugates using the high iron diamine method revealed three types of reactions in the basophil granules of all three species: granules showing a strong overall reaction, granules showing reaction only at their periphery, and granules showing no reaction. With regard to the relationship between maturation and the types of basophil granules, it appeared that, in general, there were many type-1 granules among immature basophils, but that these granules decreased in mature basophils as type-3 granules increased. The reaction patterns of periodate-reactive neutral glycoconjugates, as shown by the periodic acid-thiocarbohydrazide-silver proteinate (PA-TCH-SP) method, were different from those of acid mucopolysaccharides: the reaction of basophil granules was diffusely positive, and localization at the periphery was rarely observed. Therefore, unlike the acid mucopolysaccharides, it was difficult to classify the glycoconjugates into three types. However, as with acid mucopolysaccharides, there was a tendency for periodate-reactive glycoconjugates to decrease as maturation progressed. In terms of different species of animals, the reaction of periodate-reactive glycoconjugates with PA-TCH-SP was stronger in humans and rabbits than in guinea pigs. PMID- 2933375 TI - Testicular effects of Di-(2-ethylhexyl) phthalate (DEHP): histochemical and histopathological alterations. PMID- 2933376 TI - A modified laparoscopic approach for liver biopsy in dogs. AB - A modified laparoscopic technique for liver biopsy in dogs was developed, using an otoscope to observe the liver and to guide the biopsy needle. The procedure was used to obtain liver biopsy specimens from 7 control dogs and 22 treated dogs during studies of the hepatic effects of long-term anticonvulsant drug therapy. In addition, biopsy specimens were obtained from 10 clinical patients with diffuse liver disease. Diagnostic liver specimens were obtained from all dogs with minimal complications. The procedure used basic principles of needle biopsy technique under visual control. It enabled the operator to observe the liver, select a biopsy site, and obtain diagnostic samples quickly, with considerably less expense than by use of fiberoptic laparoscopy. The results of this study indicate that the modified laparoscopic approach is a safe, practical method for liver biopsy in dogs. PMID- 2933377 TI - An electron microscopical study of epiplexus and supraependymal cells in the prenatal rat brain following a maternal injection of 6-aminonicotinamide. AB - Epiplexus and supraependymal cells in the lateral ventricles of both normal and experimental prenatal rats were studied with the scanning and transmission electron microscopes. In normal rats, the epiplexus cells, which were predominantly spindle shaped, displayed long filopodial processes inserted into the palisade of microvilli of the choroid epithelium; their cell bodies appeared relatively smooth with occasional blebs. In experimental animals in which the mother was given an injection of 6-aminonicotinamide (6-AN), the cell bodies of the epiplexus cells became extremely ruffled or blebbed. They were seen to be actively involved in the phagocytosis of leaked erythrocytes. The behaviour of supraependymal cells was rather similar. When stimulated by a 6-AN injection, the cells showed large prominent blebs and they too were engaged in phagocytic activity. It was concluded from this study that intraventricular macrophages bearing numerous filopodia are the less active cells whereas those bearing shorter processes, in particular, blebs or ruffles, represent the active form. PMID- 2933378 TI - The nonspecificity of the lead method for the histochemical demonstration of adenosine triphosphatases in human skeletal muscle fibres. AB - The lead method for the histochemical demonstration of presumptive mitochondrial adenosinetriphosphatase was applied to biopsy and autopsy samples of the human vastus lateralis muscle. The effect of p-chloromercuribenzoate and of Triton X 100 was tested microdensitometrically and the activity of 'mitochondrial' ATPase was compared to the activity of enzymes of the oxidative metabolism succinic dehydrogenase and NAD-tetrazolium reductase. It is concluded that the ATPase activity displayed is not mainly mitochondrial. In autopsy material, it seems to be predominantly myofibrillar. PMID- 2933379 TI - Sex-related reduced weight gains in growing swine fed diets containing deoxynivalenol. AB - A 5-wk feeding trial was conducted with 30 castrated male and 28 female, 5-wk-old crossbred piglets. Three different deoxynivalenol (DON) and zearalenone (Z) contaminated diets were fed: .7, 3.1 and 5.8 ppm DON and 0, .05, and .1 ppm Z, respectively. The animals were fed their respective diets for 4 wk followed by the .7:0-ppm diet during wk 5. Feed intake and weight gain varied in a manner reciprocal to the levels of DON-Z in the diets during the first 4 wk (P less than .05). The castrated males had an overall lower weight gain compared with the females receiving the same diet (P less than .05). Gross postmortem changes were not different in either sex and tended to be most prominent in the pigs fed the lower DON:Z-contaminated diets after the first week, although they were seen in pigs fed the higher DON:Z diets after 4 wk of feeding. Lesions included mild to moderated reddening of the fundic mucosa of the stomach, reddening of the mucosa of the small intestine, and mild to moderate enlargement and edema of the mesenteric lymph nodes. Similarly, the severity of histologic changes tended to vary inversely with the concentrations of DON:Z in the diets after the first week but varied with the concentrations of DON:Z after 4 wk. They consisted of vascular congestion with mild to moderate multifocal erosions and degeneration of the mucosa in the stomach and small intestine. Mild to moderate lymphoid degeneration and depletion were also observed in the Peyer's patches of the intestines, bronchial and mesenteric lymph nodes, spleen, tonsil and thymus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2933380 TI - In-vitro evaluation of cefpirome (HR 810), teicoplanin and four other antimicrobials against enterococci. AB - In-vitro activities of cefpirome (HR 810), a fourth generation cephalosporin, and teicoplanin were compared with those of ampicillin, piperacillin, and vancomycin against 56 clinical isolates of enterococci. Cefpirome had good activity with the MIC90 and MBC90 being 4 and 16 mg/l. Ampicillin and piperacillin had MBC90 of 4 and 16 mg/l. Teicoplanin was extremely active with the MIC90 being 1.6 mg/l while vancomycin had poor cidal activity with the MBC90 being 16 mg/l. A decrease in activity of cefpirome was noted when the inoculum size was increased from 10(3) to 10(7) organisms per ml. Synergy was demonstrated against most Streptococcus faecium isolates with a combination of cefpirome and gentamicin or piperacillin. Against Str. faecalis, with a similar combination, synergy was seen in less than 50% isolates. No antagonism was noted with any of the antibiotic combinations. PMID- 2933381 TI - Efficacy and safety of ciprofloxacin (Bay 0 9867) in the treatment of patients with complicated urinary tract infections. AB - In an open study 28 patients were treated for complicated UTI with ciprofloxacin 250 mg every 12 h for 10 days. The most frequently isolated species were Escherichia coli and Klebsiella pneumoniae. All pathogens were sensitive to ciprofloxacin in vitro. Twenty-three of the 28 patients (82%) were free of infection 5-9 days after therapy. A persistent infection was noted in two patients (7%) and a reinfection in three patients (11%). Four to six weeks after the end of therapy, 18 patients (64%) were still totally free of infection. Clinical resolution of symptoms and signs occurred in 27 patients (96%). Adverse reactions were spontaneously reported by four of the 28 patients (14%) and by 11 (39%) after detailed inquiry. Most side effects were of gastrointestinal or neurological nature. This small open study supports the view, that ciprofloxacin may be useful in the treatment of complicated UTI. PMID- 2933382 TI - In-vitro activity of ciprofloxacin against clinical isolates of mycobacteria resistant to antimycobacterial drugs. AB - The activity of ciprofloxacin against 42 clinical isolates of mycobacteria was studied in vitro by the 1% standard proportion method on Lowenstein-Jensen medium. Ciprofloxacin was found active against all strains of Mycobacterium tuberculosis sensitive to streptomycin, isoniazid, ethambutol and rifampicin. The MIC of ciprofloxacin was 3.2 mg/l. This concentration of ciprofloxacin was sufficient to inhibit almost all strains showing intermediate sensitivity or resistance to one or more of the above agents. The same phenomenon was also observed with the atypical isolates. PMID- 2933383 TI - Effects of training on biochemical and functional properties of rodent neonatal heart. AB - This study was undertaken to determine biochemical and functional (in vivo) adaptations of the rodent neonatal heart in response to a training program of endurance running. Ten day-old rats were progressively trained on a treadmill (final intensity, 21 m/min, 30% grade, 1 h/day) until 75 days of age. The training program induced 14, 57, and 24% increases in relative heart mass, skeletal muscle citrate synthase activity, and whole-body maximal O2 uptake, respectively (P less than 0.05). Cardiac myosin (ATPase) and Ca2+-regulated myofibril ATPase were both reduced by approximately 15% in trained vs. sedentary animals (P less than 0.05). In the majority of trained hearts examined, the myosin isozyme profile reflected an estimated 14 +/- 3% shift toward the V3 or low ATPase isozyme. Left ventricular functional indices during submaximal exercise, derived from a fluid-filled indwelling cannula, indicated that the trained animals maintained similar left ventricular (LV) systolic pressure, LV + the time derivative of pressure, and systemic arterial mean blood pressure compared with their sedentary counterparts. These functional parameters were maintained even though the trained animals performed with lower submaximal exercise heart rate. These findings suggest that maximal exercise capacity can be enhanced in neonatal rats even though the biochemical potential for ATP degradation in the cardiac contractile system is lowered. We speculate that the trend to maintain the myosin isozyme pattern further in the direction of the V3 isozyme in the trained neonatal rat heart may reflect a means to economize cross bridge cycling while maintaining normal levels of ventricle performance at a given submaximal work load. PMID- 2933384 TI - Effects of hypercapnia on inspiratory and expiratory muscle activity during expiration. AB - Persistence of inspiratory muscle activity during the early phase of expiratory airflow slows the rate of lung deflation, whereas heightened expiratory muscle activity produces the opposite effect. To examine the influence of increased chemoreceptor drive and the role of vagal afferent activity on these processes, the effects of progressive hypercapnia were evaluated in 12 anesthetized tracheotomized dogs before and after vagotomy. Postinspiratory activity of inspiratory muscles (PIIA) and the activity of expiratory muscles were studied. During resting breathing, the duration of PIIA correlated with the duration of inspiration but not with expiration. Parasternal intercostal PIIA was directly related to that of the diaphragm. Based on their PIIA, dogs could be divided into two groups: one with prolonged PIIA (mean 0.57 s) and the other with brief PIIA (mean 0.16 s). Hypercapnia caused progressive shortening of the PIIA in the dogs with prolonged PIIA during resting breathing. The electrical activity of the external oblique and internal intercostal muscles increased gradually during CO2 rebreathing in all dogs both pre- and postvagotomy. After vagotomy, abdominal activity continued to increase with hypercapnia but was less at all levels of PCO2. The internal intercostal response to hypercapnia was not affected by vagotomy. The combination of shorter PIIA and augmented expiratory activity with hypercapnia might, in addition to changes in lung recoil pressure and airway resistance, hasten exhalation. PMID- 2933385 TI - Evaluation of clinical pharmacokinetic services provided to children and adolescents with cystic fibrosis. PMID- 2933386 TI - Chlorophyllum molybdites mushroom poisoning: a case report and review of the syndrome. PMID- 2933387 TI - Strength training by resistive exercises. PMID- 2933388 TI - Quality assurance in ambulatory care. PMID- 2933389 TI - Esophageal perforation: roentgenographic diagnosis. PMID- 2933390 TI - High blood pressure and kidney disease. PMID- 2933391 TI - Alcohol dehydrogenases in Acinetobacter sp. strain HO1-N: role in hexadecane and hexadecanol metabolism. AB - Multiple alcohol dehydrogenases (ADH) were demonstrated in Acinetobacter sp. strain HO1-N. ADH-A and ADH-B were distinguished on the basis of electrophoretic mobility, pyridine nucleotide cofactor requirement, and substrate specificity. ADH-A is a soluble, NAD-linked, inducible ethanol dehydrogenase (EDH) exhibiting an apparent Km for ethanol of 512 microM and a Vmax of 138 nmol/min. An ethanol negative mutant (Eth1) was isolated which contained 6.5% of wild-type EDH activity and was deficient in ADH-A. Eth1 exhibited normal growth on hexadecane and hexadecanol. A second ethanol-negative mutant (Eth3) was acetaldehyde dehydrogenase (ALDH) deficient, having 12.5% of wild-type ALDH activity. Eth3 had threefold-higher EDH activity than the wild-type strain. ALDH is a soluble, NAD linked, ethanol-inducible enzyme which exhibited an apparent Km for acetaldehyde of 50 microM and a Vmax of 183 nmol/min. Eth3 exhibited normal growth on hexadecane, hexadecanol, and fatty aldehyde. ADH-B is a soluble, constitutive, NADP-linked ADH which was active with medium-chain-length alcohols. Hexadecanol dehydrogenase (HDH), a soluble and membrane-bound, NAD-linked ADH, was induced 5- to 11-fold by growth on hexadecane or hexadecanol. HDH exhibited apparent Kms for hexadecanol of 1.6 and 2.8 microM in crude extracts derived from hexadecane- and hexadecanol-grown cells, respectively. HDH was distinct from ADH-A and ADH-B, since HDH and ADH-A were not coinduced; Eth1 had wild-type levels of HDH; and HDH requires NAD, while ADH-B requires NADP. NAD- and NADP-independent HDH activity was not detected in the soluble or membrane fraction of extracts derived from hexadecane- or hexadecanol-grown cells. NAD-linked HDH appears to possess a functional role in hexadecane and hexadecanol dissimilation. PMID- 2933392 TI - Chromosomal mapping in Erwinia carotovora subsp. carotovora with the IncP plasmid R68::Mu. AB - Conjugational gene transfer was established in Erwinia carotovora subsp. carotovora SCRI193 by using plasmid R68::Mu c+ to mobilize the chromosome into multiply mutant recipients. It was observed that although the plasmid alone mobilized markers randomly at a frequency of ca. 10(-5) chromosomal recombinants per donor, the presence of a Mu prophage on the chromosome of the donor increased the frequency of mobilization of markers adjacent to the prophage by up to 10 fold. Using this system it was possible to order 17 chromosomal mutations. The behavior of Mu in E. carotovora subsp. carotovora was also studied. PMID- 2933393 TI - Toxicity and mutagenicity of plumbagin and the induction of a possible new DNA repair pathway in Escherichia coli. AB - Actively growing Escherichia coli cells exposed to plumbagin, a redox cycling quinone that increases the flux of O2- radicals in the cell, were mutagenized or killed by this treatment. The toxicity of plumbagin was not found to be mediated by membrane damage. Cells pretreated with plumbagin could partially reactivate lambda phage damaged by exposure to riboflavin plus light, a treatment that produces active oxygen species. The result suggested the induction of a DNA repair response. Lambda phage damaged by H2O2 treatment were not reactivated in plumbagin-pretreated cells, nor did H2O2-pretreated cells reactivate lambda damaged by treatment with riboflavin plus light. Plumbagin treatment did not induce lambda phage in a lysogen, nor did it cause an increase in beta galactosidase production in a dinD::Mu d(lac Ap) promoter fusion strain. Cells pretreated with nonlethal doses of plumbagin showed enhanced survival upon exposure to high concentrations of plumbagin, but were unchanged in their susceptibility to far-UV irradiation. polA and recA mutants were not significantly more sensitive than wild type to killing by plumbagin. However, xth 1 mutants were partially resistant to plumbagin toxicity. It is proposed that E. coli has an inducible DNA repair response specific for the type of oxidative damage generated during incubation with plumbagin. Furthermore, this response appears to be qualitatively distinct from the SOS response and the repair response induced by H2O2. PMID- 2933394 TI - (Ca2+ + Mg2+)-ATPase activity in plasma membrane of circulating mononuclear cells. Lack of a direct effect of vitamin D. AB - The in vivo effect of vitamin D on (Ca2+ + Mg2+)-ATPase activity was examined in a plasma membrane fraction of rat circulating mononuclear cells (MPM). Although there was no significant difference in the ATPase activities in red blood cell ghosts, (Ca2+ + Mg2+)-ATPase activity in MPM was significantly higher (p less than 0.05) in long-term vitamin D3-replete rats (100 IU/day for 6 months) than that in vitamin D-deplete rats (for 6 months). In rats maintained on vitamin D deficient diets for 5-7 weeks, in vivo administration of either vitamin D3, 2,000 IU orally, 5 days prior to killing or 1,25-dihydroxyvitamin D3, 2.4 nmol, intraperitoneally, 24 h prior to killing failed to show any significant effect on (Ca2+ + Mg2+)-ATPase activity in MPM. (Ca2+ + Mg2+)-ATPase activity in MPM from rats maintained on vitamin D-deficient diet with high calcium content (1.8%) was significantly higher (p less than 0.05) than that from rats maintained on vitamin D-deficient diet with low calcium content (0.3%). Moreover, in vitro addition of vitamin D3 metabolites did not show any effect on (Ca2+ + Mg2+)-ATPase activity in MPM. These data suggest that decreased (Ca2+ + Mg2+)-ATPase activity in MPM from long-term vitamin D-deplete rats resulted from an adaptation to low extracellular calcium rather than vitamin D depletion. PMID- 2933395 TI - Phosphorylation of ankyrin decreases its affinity for spectrin tetramer. AB - The effects of phosphorylation on the interaction between spectrin and ankyrin were investigated. Spectrin and ankyrin were phosphorylated using purified human erythrocyte membrane and cytosolic (casein kinase A) kinases. These two kinases have similar properties as well as activities toward spectrin and ankyrin. Both kinases catalyzed the incorporation of about 2 mol of phosphate/mol of spectrin and about 7 mol of phosphate/mol of ankyrin. These phosphates were incorporated primarily into seryl and threonyl residues of the proteins. The phosphopeptide maps of ankyrin phosphorylated by the membrane kinase and casein kinase A were identical. Binding studies indicate that ankyrin exhibits different affinities for spectrin dimers (KD = 2.5 +/- 0.9 X 10(-6) M) and tetramers (KD = 2.7 +/- 0.8 X 10(-7) M). These dissociation constants were not appreciably affected by the phosphorylation of spectrin. On the other hand, phosphorylation of ankyrin was found to significantly reduce its affinity for either phosphorylated or unphosphorylated spectrin tetramers (KD = 1.2 +/- 0.1 X 10(-6) M) but not spectrin dimers (KD = 2.5 +/- 0.4 X 10(-6) M). The same results were obtained using either the membrane kinase or casein kinase A as the phosphorylating enzyme. The above observation suggests that ankyrin phosphorylation may provide an important mechanism for the regulation of the erythrocyte membrane cytoskeletal network. PMID- 2933396 TI - Mechanistic investigations of Escherichia coli cytidine-5'-triphosphate synthetase. Detection of an intermediate by positional isotope exchange experiments. AB - CTP synthetase from Escherichia coli catalyzes exchange of 18O from the beta gamma-bridge position of [gamma-18O4] ATP into the beta-nonbridge position. This positional isotope exchange occurs in the presence of UTP and MgCl2 but in the absence of NH3. The enzyme also has an ATPase activity in the presence of UTP that occurs under conditions that are identical to those used in the positional isotope exchange experiments. These data provide evidence for the stepwise nature of the reactions catalyzed by CTP synthetase with the initial step involving phosphorylation of UTP by ATP. The relative rate of the isotope exchange reaction is approximately 3 times faster than the ATPase reaction, but the isotope exchange rate is approximately 3% of the overall rate in the presence of NH3. These results are consistent with the ATPase reaction involving attack of water on the phosphorylated intermediate (4-phospho-UTP). The positional isotope exchange reaction is independent of the UTP concentration above saturating levels of UTP demonstrating that the order of addition of substrates is UTP followed by ATP and then NH3. PMID- 2933397 TI - Effects of low extracellular sodium on cytosolic ionized calcium. Na+-Ca2+ exchange as a major calcium influx pathway in kidney cells. AB - The effects of extracellular Na+ (Na+o) on cytosolic ionized calcium (Ca2+i) and on calcium and sodium fluxes were measured in monkey kidney cells (LLC-MK2). Ca2+i was measured with aequorin and the ion fluxes with 45Ca and 22Na. Na+-free media rapidly increased Ca2+i from 60 to a maximum of about 700 nM in 2-3 min. After the peak, Ca2+i declined and reached a plateau of about twice the resting Ca2+i. The peak Ca2+i was inversely proportional to Na+o and directly proportional to the extracellular calcium concentration (Ca2+o). On the other hand, a pH of 6.8 reduced and Ca2+o substitution with Sr2+ completely blocked the Ca2+i response to low Na+o. A Na+-free medium stimulated calcium efflux from the cells 4-5-fold, a response which was abolished in the absence of extracellular Ca2+. Na+-free media also stimulated calcium influx and sodium efflux. The cell calcium content, however, was not increased. These results indicate that removal of extracellular Na+ increases Ca2+i by stimulating calcium influx and not by inhibiting calcium efflux; the increased calcium influx takes place on the Na+ Ca2+ antiporter operating in the reverse mode in exchange for sodium efflux. The increased calcium efflux occurs as a consequence of the rise in Ca2+i and presumably takes place on the (Ca2+-Mg2+) ATPase-dependent calcium pump. PMID- 2933398 TI - Purification and properties of 3 alpha-hydroxysteroid dehydrogenase from rat brain cytosol. Inhibition by nonsteroidal anti-inflammatory drugs and progestins. AB - The 3 alpha-hydroxysteroid dehydrogenase (EC 1.1.1.50) of rat brain cytosol has been purified to apparent homogeneity. The purification procedure involves six successive steps, includes one affinity chromatography, and yields enzyme which displays a 1,550-fold enhancement in specific activity. The homogeneous enzyme has a Km of 8.0 microM for 5 alpha-dihydrotestosterone, a Vmax of 1.3 mumol of 3 alpha-androstanediol formed per h/mg of protein, and displays a preference for NADPH. It appears to be the major activity responsible for the reduction of 5 alpha-dihydrotestosterone in this tissue and may play a pivotal role in brain androgen metabolism. The homogeneous enzyme has several properties in common with the 3 alpha-hydroxysteroid dehydrogenase purified from rat liver cytosol (Penning, T. M., Mukharji, I., Barrows, S., and Talalay, P. (1984) Biochem. J. 222, 601-611). It is a monomer with a molecular weight of 31,000, it has a pI of 5.5, and it is potently inhibited by the nonsteroidal anti-inflammatory drugs (IC50 value for indomethacin = 2.0 microM). The potency of inhibition observed for the brain enzyme parallels that observed for cyclooxygenase: indomethacin greater than fenamates greater than l-methylpyrrole acetic acids greater than arylpropionic acids greater than salicylates greater than acetaminophen. Examination of a variety of steroidal contraceptives as modulators of the dehydrogenase indicates that ethinylestradiol is a very poor inhibitor (IC50 = 100 microM), while 6-medroxyprogesterone acetate (Provera) is an extremely potent inhibitor (IC50 = 0.2 microM). The possibility exists that brain androgen metabolism may be altered by the nonsteroidal anti-inflammatory drugs and synthetic progestins. PMID- 2933399 TI - Monoclonal antibodies with specific effects on partial activities of recA protein of Escherichia coli. AB - recA protein of Escherichia coli promotes a wide variety of DNA reactions in vitro. Specific effectors of recA protein should be very useful in elucidating the mechanisms of these complex reactions. Six mouse hybridoma clones that secreted class G immunoglobulins specific to recA protein were obtained in three cell-fusion experiments. Five IgGs were purified by affinity chromatography. These monoclonal antibodies were characterized by examining their effects on the single-stranded DNA-dependent ATPase activity, negatively superhelical double stranded DNA-dependent ATPase activity, and an activity in pairing negatively superhelical closed circular double-stranded DNA and homologous single-stranded DNA-fragments to form D-loops. These IgGs inhibited all, some, or one of these three activities, and from the spectra of their inhibitory effects they were classified into four groups. This classification suggests that each of the monoclonal antibodies binds to one of at least four antigenic determinants on recA protein and specifically inactivates one or more of the active centers on the protein. These monoclonal antibodies will be useful in analyzing the complex reactions promoted by recA protein. PMID- 2933400 TI - Docking of cyclohexanol-derivatives into the active site of liver alcohol dehydrogenase. Using computer graphics and energy minimization. AB - Model building and energy minimization procedures have been used to determine a productive substrate binding mode in liver alcohol dehydrogenase for secondary alcohols. These docking results have been compared to some of the extensive amounts of kinetic data available for this enzyme. The indirect diamond lattice approach first suggested by Prelog (Prelog, V. (1964) Pure Appl. Chem. 9, 119 130) to describe the active site of an enzyme has been used to build a direct diamond lattice from the crystallographic model of the enzyme. This lattice was oriented and positioned into the active site using the productive binding mode of cyclohexanol derivatives obtained from model building. We then classified the positions as allowed, forbidden, or boundary depending on their distances to protein atoms. We found very good agreement between the classification of our direct diamond lattice points and those of the indirect lattice obtained by others from kinetic studies. Finally we have extended the lattice as an aid to predict the stereospecificity of the enzyme for molecules which cover other regions of the active site. PMID- 2933401 TI - Partial purification and reconstitution of renal basolateral Na+-Ca2+ exchanger into liposomes. AB - The Na+-Ca2+ exchange system in renal tubular basolateral membranes was partially purified and incorporated into liposomes. Solubilization of basolateral membranes with 1% cholic acid in the presence of 2.5% soybean phospholipids and proteolytic treatment with Pronase (20 micrograms/ml) as described (Wakabayashi, S., and Goshima, K. (1982) Biochim. Biophys. Acta 693, 125-133) allowed partial purification and reconstitution of the Na+-Ca2+ exchange system into liposomes. The Na+-dependent Ca2+ uptake in the reconstituted liposomes was 25 times higher than the Na+-dependent Ca2+ uptake in the native basolateral membranes. Eadie Hofstee analysis of the Na+-dependent Ca2+ uptake revealed a Vmax of 201 pmol of Ca2+/mg of protein/45 s and a Km for Ca2+ of 2.7 microM. The stoichiometry (n) of the Na+-Ca2+ exchange system was determined from the Na+ gradient which opposes constant membrane potential so that no net Ca2+ transport occurs. In the presence of constant negative membrane potential, the value for n was 3.09 +/- 0.22, and in the presence of constant positive membrane potential, the value for n was 2.89 +/- 0.2. Thus, the stoichiometry of the renal Na+-Ca2+ exchange system is approximately 3Na+:1Ca2+. PMID- 2933402 TI - Solvent isotope effects and the pH dependence of laccase activity under steady state conditions. AB - Solvent isotope effects and the pH dependence of laccase catalysis under steady state conditions were examined with a rapid reductant to assess the potential roles of protein protic groups and the catalytic mechanism. The pH dependence of both reductant-dependent and reductant-independent steps showed bell-shaped profiles implicating at least two protic groups in each case. The apparent pKa values were: for the reductant-independent step(s), pK alpha 1 = 8.98 +/- 0.02 and pK alpha 2 = 5.91 +/- 0.03; for the reductant-dependent step(s), pK' alpha 1 = 7.55 +/- 0.12, pK' alpha 2 = 8.40 +/- 0.23. No solvent isotope effect on reductant-dependent steps was detected other than a standard shift effect. However, a significant solvent isotope effect on a reductant-independent step(s) was observed; kH/kD = 2.12 at the pH optimum of 7.5. The concentration dependence of the D2O effect indicated that a single proton was involved. Simulations of the p(H,D) data suggested that the solvent isotope effect was associated with the protein protic group required in its undissociated form (pK alpha 2). The pH effects on reductant-dependent steps are apparently associated with reductant dependent steps that occur between O2 binding and water formation in the catalytic reaction sequence. PMID- 2933403 TI - Mechanism of the phosphorylation-dependent regulation of smooth muscle heavy meromyosin. AB - Phosphorylation of smooth muscle heavy meromyosin (HMM) has been shown to result in about a 25-fold increase in the steady-state Vmax of the actin-activated MgATPase activity from 0.07 s-1 for unphosphorylated HMM to 1.9 s-1 for phosphorylated HMM. The steady-state MgATPase activity of unphosphorylated HMM in the absence of actin is 0.004 s-1. The true extent of regulation might be even larger since the actin activation of the MgATPase activity of unphosphorylated HMM (from 0.004 to 0.07 s-1 at Vmax) could be arising from a small fraction of modified HMM molecules which are no longer regulated and that truly regulated unphosphorylated HMM molecules are not activated by actin. To test this idea, a "limited turnover" experiment was used to measure the reassociation rate of acto unphosphorylated HMM following addition of a 2-4-fold molar excess of ATP. The reassociation rate was very slow and was not significantly increased by raising the actin concentration from 10 to 75 microM or by addition of trace phosphorylated HMM. The rate constant was estimated to be about 0.002 s-1, which is in good agreement with the rate of product (both Pi and ADP) release estimated from unphosphorylated HMM alone measured by a gel filtration technique. These two experiments suggest that the rate of product release from unphosphorylated HMM may not be significantly affected by actin and that perhaps the true extent of regulation of HMM by phosphorylation is much greater than that determined by steady-state methods. It also suggests that phosphorylation may operate by increasing the forward rate constant for product release by approximately 1000 fold. PMID- 2933404 TI - Mechanism of smooth muscle myosin phosphorylation. AB - In vertebrate smooth muscles, phosphorylation of the regulatory light chain appears to be necessary for actin activation of the Mg-ATPase activity and for the in vitro assembly of myosin into filaments. From a correlation between the degree of phosphorylation and enzymatic activity, it was suggested that both myosin heads must be phosphorylated before either head could be activated by actin, and that phosphorylation of filamentous myosin occurred in a negatively cooperative manner (Persechini, A., and Hartshorne, D. J. (1981) Science 213, 1383-1385; Ikebe, M., Ogihara, S., and Tonomura, Y. (1982) J. Biochem. (Tokyo) 91, 1809-1812; Sellers, J. R., Chock, P. B., and Adelstein, R. S. (1983) J. Biol. Chem. 258, 14181-14188). Here we have determined the mechanism of phosphorylation by separating dephosphorylated and phosphorylated myosin species based on their different structural properties in the minifilament buffer system (5 mM citrate, 22 mM Tris). Fully phosphorylated myosin remained assembled as minifilaments in 1 mM Mg-ATP, but dephosphorylated myosin dissociated to a mixture of folded monomers and dimers. Gel filtration was used to separate these two structures. At intermediate levels of phosphorylation, the relative amount of myosin that formed minifilament and dimer and the degree of phosphorylation of the separated species relative to the initial level of phosphorylation was measured. From these data, it was possible to deduce that singly and doubly phosphorylated myosin remained assembled in the presence of nucleotide. Myosin molecules with 0, 1, or 2 heads phosphorylated could also be separated by nondenaturing gel electrophoresis. The amount of myosin which formed each species was quantitated as a function of phosphorylation. Results from the combined approaches are consistent with a model in which light chain kinase randomly phosphorylates myosin, independent of the state of aggregation of the myosin. PMID- 2933405 TI - Conformational changes of the Ca2+-ATPase as early events of Ca2+ release from sarcoplasmic reticulum. AB - Rabbit skeletal sarcoplasmic reticulum vesicles were loaded with Ca2+ by ATP dependent Ca2+ accumulation in the presence of low [Mg2+] (0.2-0.5 mM), and Ca2+ release was induced by addition of caffeine or ADP or by means of a Ca2+ jump. The levels of the phosphorylated intermediate (EP) and the tryptophan fluorescence of the Ca2+-ATPase were monitored during both the Ca2+ accumulation and the induced Ca2+ release using fast kinetic techniques. During Ca2+ uptake, both the EP level and the tryptophan fluorescence gradually decreased following a time course similar to that of the Ca2+ accumulation. Upon inducing Ca2+ release by addition of either caffeine or ADP, there was a transient increase of the EP level (from 0.3-0.5 to 1-2 nmol/mg protein) preceding the release of Ca2+. Similarly, a transient increase of the tryptophan fluorescence prior to Ca2+ release produced by the application of a Ca2+ jump was also found. These results indicate that the Ca2+-ATPase enzyme undergoes a rapid conformational change in response to triggering of Ca2+ release. PMID- 2933406 TI - Purification of the three nuclear RNA polymerases from Neurospora crassa. AB - Nuclear RNA polymerases I, II, and III from Neurospora crassa have been purified 3,000-, 1,500-, and 10,000-fold, respectively, by a procedure that minimizes proteolysis of the 220-kDa subunit of polymerase II. The Neurospora enzymes resemble, in polypeptide composition, the corresponding polymerases isolated from other eukaryotes. The 220-kDa subunit of Neurospora polymerase II cross-reacts with antisera directed against the 220-kDa subunits of type II polymerases from Drosophila and wheat germ. However, the proteolyzed 180-kDa derivative of the Neurospora 220-kDa subunit fails to cross-react with the heterologous antisera, suggesting that the region removed by proteolysis contains or contributes to structural features of the enzyme that have been highly conserved during evolution. A 700-kDa complex of 12 polypeptides was found associated with polymerase II during purification. The complex was eventually separated from the enzyme, and its properties suggest that it might be associated with polymerase II in the nucleus. We describe two additional examples of polypeptides associated in variable amounts with Neurospora polymerase II. PMID- 2933407 TI - Structural studies on Neurospora RNA polymerases and associated proteins. AB - Extensive structural homology between the three nuclear RNA polymerases of Neurospora crassa has been observed by peptide and immunological analyses. Within each polymerase, we found structural similarity between subunits in the 65- to 75 kDa range and one of the two large subunits. We observed also that polymerase II, as isolated, is associated with a 700-kDa complex of 12 polypeptides which is localized in the nucleus. A 75-kDa subunit of the 700-kDa complex was found to be structurally related to the 220-kDa subunit of polymerase II. We suggest, on the basis of the in vitro association, the common nuclear localization and the structural homology, that the 700-kDa complex and polymerase II may be associated in vivo. Evidence is also presented which suggests that polymerase III may interact with chromatin via two of its smallest subunits. A simple procedure for isolating nuclei from Neurospora is described. PMID- 2933408 TI - Wave propagation across a bony discontinuity simulating a healing fracture. AB - Stress wave propagation in a long bone with a progressively increasing defect in the bony cortex, simulating a healing fracture, was studied by recording the outputs of bonded semiconductor strain gages, proximal and distal to the defect. Statistically significant relations were found between the relative size of the discontinuity and the transmission coefficient, dispersion and transit time across the fracture. We also showed that the stress wave in a bone could be monitored from the vibration response of a traction pin, placed in a magnetic field. The results may be helpful for the development of new methods to measure the rate of fracture healing, as well as aiding our understanding of the dynamic loading of bone. PMID- 2933409 TI - Experimental study of physiological pulsatile flow past valve prostheses in a model of human aorta--I. Caged ball valves. AB - Pulsatile flow development past a caged ball valve in a model human aorta was studied using laser Doppler anemometry. Velocity profiles measured in the ascending aorta and in the mid-arch region were strongly influenced by the geometry of the valve at the root of the aorta. Velocity profiles distal to the valve were asymmetric with jet-like flow in the peripheral region having larger velocity magnitudes towards the left lateral wall. In early diastole, a streamwise vortex motion was observed throughout the model aorta with fluid moving towards the downstream direction along the left lateral wall and reversed flow along the right lateral wall. With the caged ball valve at the root of the aorta, no reversed flow was observed along the inner wall of curvature in the mid arch region. PMID- 2933410 TI - Velocity profiles in the wake of two prosthetic heart valves using a new cardiovascular simulator. AB - In this paper we present a study of the post valvular flow field on a new cardiovascular simulator including an elastic model of the aortic arch. Transverse and vertical two-dimensional velocity measurements are performed with an ultrasonic velocimeter. Two prosthetic heart valves are tested in the aortic position. The behaviour of the velocity vectors patterns during one pulsatile cycle is one of the most striking features of the flow. PMID- 2933411 TI - Detection of arterial stenosis: increased accuracy using biplanar angiography and Doppler signal analysis. AB - Femoral artery Doppler signals were analysed from 68 patients with lower limb ischaemia undergoing biplanar angiography. These studies (pulsatility index, P.I. and LaPlace transform damping, LTD) were compared with clinical examination using this biplanar angiographic standard. Accuracy of femoral pulse palpation in predicting upstream stenosis was 67%. Biplanar angiography unmasked single plane stenosis underestimates in 21% of patients. In a subgroup of 39 lower limbs with aorto-iliac stenoses between 26 and 85% femoral LTD was the best predictor, being 84% accurate: whereas PI did not improve upon clinical examination. The need for biplanar angiography is underlined and the place of Doppler signal analysis in the assessment of arterial stenosis is confirmed. PMID- 2933412 TI - Multiple aneurysmal dilatations in a knitted dacron velour graft. AB - The formation of multiple aneurysms in the midportion of Dacron grafts has been reported only twice in the surgical literature. In the present case, three aneurysmal dilatations developed 6 years following an orto-femoral Dacron graft implantation. Multiple structural defects in the Dacron prosthesis appear to be the most likely cause of the graft failure. PMID- 2933413 TI - The cell substrate attachment (CSAT) antigen has properties of a receptor for laminin and fibronectin. AB - The cell substrate attachment (CSAT) antigen is an integral membrane glycoprotein complex that participates in the adhesion of cells to extracellular molecules. The CSAT monoclonal antibody, directed against this complex, inhibited adhesion of cardiac and tendon fibroblasts and skeletal myoblasts to both laminin and fibronectin, thus implicating the CSAT antigen in adhesion to these extracellular molecules. Equilibrium gel filtration was used to explore the hypothesis that the CSAT antigen functions as a cell surface receptor for both laminin and fibronectin. In this technique, designed for rapidly exchanging equilibria, the gel filtration column is pre-equilibrated with extracellular ligand to ensure receptor occupancy during its journey through the column. Both laminin and fibronectin formed complexes with the CSAT antigen. The association with laminin was inhibited by the CSAT monoclonal antibody; the associations with both fibronectin and laminin were inhibited by synthetic peptides containing the fibronectin cell-binding sequence. Estimates of the dissociation constants by equilibrium gel filtration agree well with those available from other measurements. This suggests that these associations are biologically significant. SDS PAGE showed that all three glycoproteins comprising the CSAT antigen were present in the antigen-ligand complexes. Gel filtration and velocity sedimentation were used to show that the three bands comprise and oligomeric complex, which provides an explanation for their functional association. The inhibition of adhesion by the CSAT monoclonal antibody and the association of the purified antigen with extracellular ligands are interpreted as strongly implicating the CSAT antigen as a receptor for both fibronectin and laminin and perhaps for other extracellular molecules as well. PMID- 2933414 TI - Membrane and cytoskeletal changes associated with IgE-mediated serotonin release from rat basophilic leukemia cells. AB - Binding of antigen to IgE-receptor complexes on the surface of RBL-2H3 rat basophilic leukemia cells is the first event leading to the release of cellular serotonin, histamine, and other mediators of allergic, asthmatic, and inflammatory responses. We have used dinitrophenol-conjugated bovine serum albumin (DNP-BSA) as well as the fluorescent antigen, DNP-B-phycoerythrin, and the electron-dense antigen, DNP-BSA-gold, to investigate dynamic membrane and cytoskeletal events associated with the release of [3H]serotonin from anti-DNP IgE-primed RBL-2H3 cells. These multivalent antigens bind rapidly to cell surface IgE-receptor complexes. Their distribution is initially uniform, but within 2 min DNP-BSA-gold is found in coated pits and is subsequently internalized. Antigen internalization occurs in the presence and absence of extracellular Ca2+. The F actin content of the detergent-extracted cell matrices analyzed by SDS PAGE decreases during the first 10-30 s of antigen binding and then increases by 1 min to almost double the control levels. A rapid and sustained increase is also observed when total F-actin is quantified by flow cytometry after binding of rhodamine-phalloidin. The antigen-stimulated increase in F-actin coincides with (and may cause) the transformation of the cell surface from a finely microvillous to a highly folded or plicated topography. Other early membrane responses include increased cell spreading and a 2-3-fold increase in the uptake of fluorescein dextran by fluid pinocytosis. The surface and F-actin changes show the same dependence on DNP-protein concentration as stimulated [3H]serotonin release; and both the membrane responses and the release of mediators are terminated by the addition of the non-cross-linking monovalent ligand, DNP-lysine. These data indicate that the same antigen-stimulated transduction pathway controls both the membrane/cytoskeletal and secretory events. However, the membrane and actin responses to IgE-receptor cross-linking are independent of extracellular Ca2+ and are mimicked by phorbol myristate acetate, whereas ligand-dependent mediator release depends on extracellular Ca2+ and is mimicked by the Ca2+ ionophore A23187. PMID- 2933415 TI - Surface functions during mitosis in rat basophilic leukemia cells. AB - At the entry into mitosis, cells abruptly lose membrane activities such as phagocytosis, pinocytosis, and capping. The present studies test if mitotic cells also resist functional responses to cell surface ligand-receptor interactions. The IgE receptors of RBL-2H3 rat basophilic leukemia cells were labeled with anti dinitrophenol IgE (anti-DNP-IgE) and then cross-linked with multivalent ligands (DNP-bovine serum albumin [BSA]; DNP-B-phycoerythrin; DNP-BSA-gold). IgE-receptor cross-linking modulates cell surface organization and function and releases serotonin and other mediators of allergic and asthmatic reactions from interphase cells (Pfeiffer, J. R., JC. Seagrave, B. H. Davis, G. G. Deanin, and J. M. Oliver, 1985, J. Cell Biol., 101:2145-2155). It was found that anti-DNP-IgE receptor complexes are preserved on the cell surface throughout mitosis; they continue to bind DNP-proteins, and the resulting antigen-IgE-receptor complexes can redistribute to coated pits on the cell surface. Furthermore, there is no loss of [3H]serotonin through mitosis. Nevertheless, antigen-stimulated [3H] serotonin release is strongly impaired in mitotic-enriched as compared with mixed interphase or G1-enriched cell populations. In addition, antigen binding transforms the surface of interphase cells from a microvillous to a plicated topography and stimulates the uptake of fluorescein isothiocyanate-conjugated dextran by fluid pinocytosis. Mitotic cells maintain a microvillous surface topography after antigen treatment, and fluid pinocytosis virtually ceases from prometaphase to telophase. Phorbol myristate acetate, a tumor promoter that activates protein kinase C, restores surface ruffling activity to mitotic cells. Thus, the mitosis-specific freezing of membrane and secretory responses is most likely due to the failure of transmembrane signaling. PMID- 2933417 TI - Characteristics of a BHK cell variant defective in the cell-substratum contact process. AB - In this paper we document the phenotypic characteristics of a novel BHK cell adhesion variant designated FN-2. Unlike parental cells, FN-2 cells did not attach to fibronectin (pFN)-coated dishes, even after 4-hr incubations on dishes treated with 100 micrograms/ml of pFN. Mixing experiments with the variant and parental cells revealed that the parental cells attached normally in the presence of a ninefold excess of variant cells and the variant cells failed to attach in the presence of a ninefold excess of parental cells. Therefore, the defect in FN 2 cells could not be explained by secretion of a factor inhibiting attachment or lack of secretion of a factor required for attachment. Also, the inability of FN 2 cells to attach to pFN-coated dishes could not be explained by an absence of cell pFN receptors since the variant cells bound normal numbers of small (ca. 0.8 micron) pFN-coated latex beads, although they phagocytosed the beads poorly compared to parental cells. Also, the variant cells were not able to bind large (5.7 or 16.8 microns) pFN-coated beads. When tested on dishes coated with ligands that, unlike fibronectin, have a high affinity for cell surface receptors, e.g., lectins and anti-BHK antibodies, FN-2 cells were observed to attach at a rate similar to that of parental cells but spread much more slowly. The phenotypic characteristics of FN-2 cells suggest that they are deficient in what previously has been called the "cell contact" process in cell adhesion. It is proposed that the cell contact process is the initial formation by an individual cell of a sufficient number of cell-substratum bonds to resist the shear forces operationally used to define "attachment," and that more cell-substratum bonds are necessary for cell attachment to large substrata (dishes or large beads) than for attachment to small substrata (small beads). The molecular defect in FN-2 cells was studied by electroblotting analysis. A high molecular weight (ca. 370 kd) glycoprotein detected by blotting with anti-BHK antibodies and ConA that was present in parental cell membranes was reduced or absent in the variant cells. PMID- 2933418 TI - Ankyrin and synapsin: spectrin-binding proteins associated with brain membranes. AB - Brain membranes contain an actin-binding protein closely related in structure and function to erythrocyte spectrin. The proteins that attach brain spectrin to membranes are not established, but, by analogy with the erythrocyte membrane, may include ankyrin and protein 4.1. In support of this idea, proteins closely related to ankyrin and 4.1 have been purified from brain and have been demonstrated to associate with brain spectrin. Brain ankyrin binds with high affinity to the spectrin beta subunit at the midregion of spectrin tetramers. Brain ankyrin also has binding sites for the cytoplasmic domain of the erythrocyte anion channel (band 3), as well as for tubulin. Ankyrins from brain and erythrocytes have a similar domain structure with protease-resistant domains of Mr = 72,000 that contain spectrin-binding activity, and domains of Mr = 95,000 (brain ankyrin) or 90,000 (erythrocyte ankyrin) that contain binding sites for both tubulin and the anion channel. Brain ankyrin is present at about 100 pmol/mg membrane protein, or about twice the number of copies of spectrum beta chains. Brain ankyrin thus is present in sufficient amounts to attach spectrin to membranes, and it has the potential to attach microtubules to membranes as well as to interconnect microtubules with spectrin-associated actin filaments. Another spectrin-binding protein has been purified from brain membranes, and this protein cross-reacts with erythrocyte 4.1. Brain 4.1 is identical to the membrane protein synapsin, which is one of the brain's major substrates for cAMP-dependent and Ca/calmodulin-dependent protein kinases with equivalent physical properties, immunological cross-reaction, and peptide maps. Synapsin (4.1) is present at about 60 pmol/mg membrane protein, and thus is a logical candidate to regulate certain protein linkages involving spectrin. PMID- 2933416 TI - Possible pathways for lysosomal enzyme delivery. AB - Immunogold double-labeling and ultrathin cryosections were used to compare the subcellular distribution of albumin, mannose 6-phosphate receptor (MPR), galactosyltransferase, and the lysosomal enzymes cathepsin D, beta hexosaminidase, and alpha-glucosidase in Hep G2 cells. MPR and lysosomal enzymes were found throughout the stack of Golgi cisternae and in a trans-Golgi reticulum (TGR) of smooth-surfaced tubules with coated buds and vesicles. The trans-Golgi orientation of TGR was ascertained by the co-localization with galactosyltransferase. MPR was particularly abundant in TGR and CURL, the compartment of uncoupling receptors and ligands. Both TGR and CURL also contained lysosomal enzymes, but endogenous albumin was detected in TGR only. The coated buds on TGR tubules contained MPR, lysosomal enzymes, as well as albumin. MPR and lysosomal enzymes were also found in coated pits of the plasma membrane. CURL tubules seemed to give rise to smooth vesicles, often of the multivesicular body type. In CURL, the enzymes were found in the lumina of the smooth vesicles while MPR prevailed in the tubules. These observations suggest a role of CURL in transport of lysosomal enzymes to lysosomes. When the cells were treated with the lysosomotropic amine primaquine, binding of anti-MPR to the cells in culture was reduced by half. Immunocytochemistry showed that MPR accumulated in TGR, especially in coated buds. Since these buds contain endogenous albumin and lysosomal enzymes also, these data suggest that coated vesicles originating from TGR provide for a secretory route in Hep G2 cells and that this pathway is followed by the MPR system as well. PMID- 2933420 TI - The effects of mentally handicapped children on families--a conceptual review. AB - Recent research which examines the effects of mentally handicapped children upon families is reviewed. The studies are grouped into three categories based on the underlying conceptions which appear to guide them. The first category examines which families are most vulnerable to the presumed stress of a mentally handicapped child. The second category emphasises the material and practical problems families experience. The third category stresses the competence of families and describes the resources used to develop coping strategies. Links are drawn between these three categories and to parallel developments in related areas, and implications for future research are discussed. PMID- 2933419 TI - [Postoperative eventrations. Apropos of 247 surgically treated cases]. AB - The 247 eventrations operated upon concerned 230 patients (60% women and 40% men) mean age 54.5 years. Eventrations were large (collar greater than 10 cm) in 18, 5% and were in the median line in 81%. Serial laparotomies by the same approach had been performed in 21%, the principal causes of eventration being biliary and gynecologic surgery. Parietal sepsis developed in 31,5% of cases after operation for the original affection. Classical favoring factors found included obesity (51%), multiparity (42% of women) and chronic lung disease (14%). Preoperative preparation involved the use of Goni Moreno's progressive pneumoperitoneum in 18,5% of patients. Procedures used were parietal repair by raphe (22%), the same but with the addition of a dacron prosthesis (6%) or the large dacron tulle prosthesis for wide reinforcement of the visceral sac (67% of cases). Early sepsis was a slightly more frequent occurrence after dacron tulle, predisposing factors being the prosthesis itself, a previous history of parietal sepsis, swabs and the number of Redon tubes. After use of dacron tulle complications were mainly also hematoma (3.2%) and skin necrosis (2,6%). Postoperative course in general was uncomplicated in 91% of the 247 operations. Follow up of 67% of operated patients for a mean of 5 1/2 years showed recurrence in 50% of raphe procedures and 18.5% of prosthesis implantations; factors of aseptic recurrence (16,5%) were multiparity and chronic lung disease. Delayed sepsis after dacron tulle use affected 8% of patients and were related to chronicity of early sepsis, nonresorbable sutures and sepsis complicating the primary laparotomy. Doming of the parietal wall was noted in 4% of cases repaired by prosthesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2933421 TI - The temperament of Down's syndrome toddlers and their siblings. AB - The Toddler Temperament Scale was completed by mothers of 37 Down's syndrome children. Questionnaires were also completed for 13 siblings. Comparisons with standardization scores on the difficult dimensions suggested that the Down's syndrome children were more rhythmic, less intense and of more positive mood than children of the same CA. In addition, they were less withdrawn and more adaptable than children of similar MA. The siblings were more rhythmic than the standardization sample and more persistent than the Down's syndrome children. There was no trend for Down's syndrome ratings to be strongly associated with own sibling ratings. PMID- 2933422 TI - Hyperendorphinemia in obese children and adolescents. AB - To study the role of opioid peptides in human obesity, plasma beta-endorphin (beta EP), beta-lipotropin (beta LPH), and cortisol resting values, circadian rhythms, and responses to hypoglycemia were studied in 6 prepubertal and 6 pubertal obese adolescents (at least 40% above ideal body weight) and in 10 normal subjects matched for age, sex, and pubertal development. Baseline plasma beta LPH and beta EP concentrations in both obese children and adolescents were twice as high as those in normal controls, while cortisol levels were not different. Cortisol, beta EP, and beta LPH levels had a clear circadian rhythmicity in all subjects, with the exception of obese pubertal boys whose plasma beta EP concentrations were constant throughout the day. After insulin administration, the fall in blood sugar was similar in all groups. Plasma cortisol and beta EP responses were similar in both obese and normal prepubertal subjects. In obese pubertal adolescents, beta EP did not increase significantly after hypoglycemia, although it did increase in normal weight pubertal subjects. In normal prepubertal subjects, the circadian rhythms of beta EP and beta LPH secretion and release induced by hypoglycemia suggest the presence of a well developed neuroendocrine control of proopiomelanocortin-related peptide secretion. In prepubertal obese children, the increased plasma beta EP and beta LPH levels with the maintenance of their circadian rhythm and responsivity to hypoglycemia suggest overactivity of anterior pituitary secretion. In obese adolescents, in spite of the normal rhythm of beta LPH and cortisol, beta EP levels did not change throughout the day, thus suggesting beta EP secretion from nonpituitary sources in these subjects. The present study indicates a possible direct role for hyperendorphinemia in the induction of overeating in obese children and adolescents. PMID- 2933423 TI - Pulsatile gonadotropin-releasing hormone treatment in idiopathic delayed puberty. AB - Idiopathic delayed male puberty is defined as a delay of puberty beyond the age of 16, with prepubertal testosterone levels, normal gonadotropin responses to GnRH (excluding pituitary failure), and normal androgen responses to a single hCG injection (excluding testicular Leydig cell dysfunction), in absence of serious disease. Ten boys with this condition were evaluated as to their spontaneous LH, FSH, and PRL secretory patterns during a 24-h sampling period (20-min intervals). After this all patients were treated with pulsatile infusions of GnRH (25 ng/kg . pulse every 90 min for 10 days. Two groups could be distinguished by means of their pretreatment LH secretory pattern. Five patients had nighttime pulsatile elevation of LH levels, as usually occurs in early puberty. The other five patients did not have such a pattern (prepubertal type). The GnRH treatment resulted in increased LH and testosterone levels in both groups. All patients with pretreatment nighttime pulsatile LH secretion had steady pubertal development during the post-GnRH treatment observation period, whereas the other patients did not. In conclusion, among a number of tests, including chronic pulsatile GnRH treatment for 10 days, only the nocturnal LH secretory pattern differentiated delayed puberty from permanent hypothalamic hypogonadism in boys. PMID- 2933424 TI - Agar media that indicate acid production from sorbitol by oral microorganisms. AB - Two varieties of agar medium (Trypticase [BBL Microbiology Systems]-serum sorbitol-bromcresol purple agar [TSSB] and Trypticase-blood-sorbitol-CaCO3 agar [TBSCa]) indicating microbial acid production from sorbitol were tested. The media were devised for use in studies on the prevalence of sorbitol-fermenting human oral microorganisms incubated in an anaerobic or microaerophilic atmosphere containing 5 to 6% CO2. TSSB contains bromcresol purple as the pH indicator and NaHCO3 as the main buffering salt. TBSCa contains CaCO3 as both the buffering salt and the indicator of acid production. The growth yield of pure cultures of oral microorganisms on TBSCa was shown to equal that on blood agar incubated under similar conditions. TSSB inhibited the growth of several bacteria to various extents. The recovery of sorbitol-fermenting microorganisms from oral specimens was the greatest when the specimens were assayed with TBSCa. The poorer results obtained with TSSB were mainly due to the decoloration of the pH indicator in this medium and the presence of greater numbers of sorbitol false positive colonies. PMID- 2933425 TI - Inhibition of tension development and actomyosin ATPase activity in barnacle muscle by the Ca2+-indicator dye antipyrylazo III. AB - We have investigated the effects of the Ca2+-indicator dye antipyrylazo III on: (1) tension development in myofibrillar preparations from barnacle depressor muscle; and (2) actomyosin ATPase activity in myofibrils/native actomyosin isolated from barnacle muscle and in actomyosin hybrids prepared from pure (unregulated) rabbit F-actin and purified barnacle myosin. In all solutions, pCa was either heavily buffered with suitable [CaEGTA]/[EGTA] and/or measured with a calcium-electrode so as to offset the appreciable Ca2+-buffering effects of the dyes. Antipyrylazo III produced a rapid, reversible and concentration-dependent inhibition of: (1) tension development by isolated barnacle myofibrils; (2) calcium-regulated ATPase activity in barnacle myofibrils and native actomyosin; and (3) calcium-independent actin-activated ATPase activity in hybrid actomyosins prepared from purified barnacle myosin and rabbit actin. This latter observation indicated that the inhibitory effect of the dye on calcium-regulated tension and ATPase in intact myofibrils is due to specific repression of active crossbridge formation rather than modification of calcium-regulatory mechanisms. The hypothesis that antipyrylazo III specifically represses active crossbridge formation was supported by the observation that the dye had no effect on rigor tension development. Specific and saturable binding of the dye to these myofibrils was characterized by a maximum capacity of 1.3 mumol dye g-1 myofibrillar protein, consistent with a calculated 1 dye: 1 myosin stoichiometry. These various biological effects were observed with both commercially available antipyrylazo III and highly purified dye preparations. Preliminary studies using myofibrillar preparations from rabbit psoas muscle, guinea-pig portal vein smooth muscle, and scallop adductor muscle have indicated that contractile function in these muscle types does not appear to be inhibited by antipyrylazo III. PMID- 2933426 TI - Avian adductor profundus muscle: characterization of a pure slow tonic region by histochemical, monoclonal antibody and peptide mapping studies. AB - The fibre type composition of the avian adductor profundus (AP) muscle which is composed of a thick white posterior part (Post. AP) and a thin red anterior part (Ant. AP) was investigated. Using the histochemical ATPase technique, monoclonal antibody analysis of myosin and C-protein isoforms, and electrophoretic and peptide mapping analyses of myosin, we have established that the Post. AP is composed of essentially pure slow tonic fibres similar to those of the anterior latissimus dorsi muscle (ALD). The Ant. AP, on the other hand, is shown to contain a mixture of slow and fast fibres, the latter giving immunocytochemical reactions atypical of the fast fibres. The larger size of the Post. AP in comparison with the ALD muscle should provide significantly more tissue for biochemical studies of tonic fibres than was previously available. PMID- 2933427 TI - The isoforms of C protein and their distribution in mammalian skeletal muscle. AB - A monoclonal antibody that is specific for the slow skeletal muscle isoform of C protein of rabbit muscle has been prepared by immunizing mice with a crude preparation of human myosin. It reacted with the X protein fraction of rabbit skeletal muscle and stained all type I cells in this tissue. It also stained a fraction of the type II cells with varying intensities. The type II cells staining with antibody to slow C protein also stained with a polyclonal antibody prepared against rabbit fast muscle C protein. The type II cells not staining with antibody to slow C protein stained strongly with antibody to fast C protein. In the human skeletal muscle antibody to slow C protein stained all cells whereas antibody to fast C stained only type II cells. It is concluded that the distribution of the isoforms of C protein in adult vertebrate skeletal muscle is more complex than is the case with proteins such as components of the troponin complex. PMID- 2933428 TI - Extrapyramidal signs following zimelidine overdose. AB - A 35-year-old woman with depression attempted suicide by taking an overdose of zimelidine (5 g), which was confirmed by zimelidine and norzimelidine plasma levels. Physical examination and repeat EKGs performed 2, 6, 9, and 12 hours later showed no alteration in her level of consciousness and only a slight increase in QT duration. However, the patient exhibited a distinct extrapyramidal syndrome, a finding consistent with animal data suggesting that zimelidine may possess some dopamine-receptor blockade properties. PMID- 2933429 TI - Dietary related periodontitis and oro-nasal fistulation in rats. AB - An outbreak of periodontitis and oro-nasal fistulation in rats in a routine long term bioassay is described. There was strong circumstantial and pathological evidence that the lesions were caused by long pointed food fibres present in an expanded diet which was fed as a powder. PMID- 2933430 TI - Palmoplantar hyperkeratosis in mycosis fungoides. AB - The association of palmoplantar hyperkeratosis and mycosis fungoides (MF) has been described less frequently in the dermatologic literature. We present a patient with MF who developed hyperkeratosis of the palms and soles. Histologic examination of a specimen from the left palm showed microscopic changes of MF. PMID- 2933431 TI - Porokeratosis punctata palmaris et plantaris (punctate porokeratosis). Case report and literature review. AB - A case of porokeratosis punctata palmaris et plantaris (punctate porokeratosis) in a 60-year-old man of Korean ancestry is reported. The patient presented with a 15-year history of numerous asymptomatic pits measuring 1 to 3 mm in diameter and having keratotic plugs irregularly distributed on the plantar aspects of both feet and on the palmar aspects of both hands, including the flexor portions of the digits. Histologic examination revealed distinct epidermal depressions containing cornoid lamellae. Six previous case reports of this unusual dermatosis are reviewed and compared to our case. PMID- 2933432 TI - A 20,000-dalton casein fragment in human milk. AB - A new peptide of 20,000 daltons was found in human milk as a constituent of the casein micelle. Enzymic digestion with plasmin or trypsin revealed that the peptide was identical with a degradation product of human beta-casein. The amino acid composition of the degradation product and the previously reported sequence in the N-terminal region of human beta-casein suggested that the peptide was a fragment of beta-casein lacking the C-terminal region. The thermal sensitivity of this peptide was higher than that of beta-casein, but the peptide lost the property of calcium-dependent precipitation, which intact beta-casein possesses. PMID- 2933433 TI - Immunosuppressive activity of bovine seminal plasma on bovine lymphocytes in vitro. AB - Pooled seminal plasma obtained from six bulls was tested for its immunosuppressive activities in vitro on blastogenesis of bovine lymphocytes. Lymphocyte stimulation assay and mixed lymphocyte reaction were used as test procedures. Concanavalin A and phytohemagglutinin were utilized in the lymphocyte stimulation assays as nonspecific stimuli. Tritiated thymidine uptake by the lymphocytes was measured after incubation for 5 d with seminal plasma. Undiluted seminal plasma was cytotoxic to lymphocytes up to and at 1/100 dilution but not at 1/400. Undiluted seminal plasma was immunosuppressive at a 1/400 dilution. Lyophilization of seminal plasma without prior dialysis resulted in loss of immunosuppressive activity. After dialysis and lyophilization, the reconstituted seminal plasma suppressed thymidine uptake by Concanavalin A and phytohemagglutinin-stimulated bovine lymphocytes while being noncytotoxic. This paper documents that bovine seminal plasma is immunosuppressive and also cytotoxic to the bovine cells that generate an immune response. PMID- 2933434 TI - Identification of an immunosuppressive protein in bovine seminal plasma with activity against bovine lymphocytes. AB - Seminal plasma was determined to have immunosuppressive activities in vitro on Concanavalin A-induced blastogenesis of bovine lymphocytes. This immunosuppressive activity was isolated and characterized using a pool of seminal plasma from five bulls. The immunosuppressive activity was associated with seminal plasma proteins of less than 50,000 daltons and also with those of approximately 150,000 daltons. The 150,000-dalton proteins were precipitable at 33% saturation with ammonium sulfate and with an antibody to a Sephadex G-200 chromatographic fraction of seminal plasma. The immunosuppressive activity of the less than 50,000 dalton proteins was lost upon chromatography on Sephadex G-25. This suggests that interaction of several components of low molecular weight might be necessary for this inhibitory activity to be expressed. PMID- 2933435 TI - Papillon-Lefevre syndrome: report of case. PMID- 2933437 TI - Dental examination guidelines for children requiring infective endocarditis prophylaxis. PMID- 2933436 TI - Pulmonary function after transverse or midline incision in patients with obstructive pulmonary disease. AB - Atelectasis and bronchopneumonia occur frequently in patients undergoing aorto iliac reconstructive surgery. Transverse (T) incisions in upper abdominal surgery are thought to be followed by fewer pulmonary complications than midline incisions (M) but reports remain controversial. We studied the incidence of postoperative pulmonary complications and lung dysfunction after T and M incisions for aorto-iliac surgery in 13 patients with chronic obstructive pulmonary disease (COPD) and 13 control patients with normal lungs (C). For all subjects, we evaluated (1) postoperative clinical or radiological pulmonary events; (2) preoperatively and on postoperative days 2 (D2), 5 (D5), 9 (D9) and 12 (D12) - the forced expiratory volume in 1 s (FEV1), vital capacity (VC), alveolar-arterial oxygen difference (AaPO2), and (3) convenience for the surgeon. Operatively, aortic exposure was excellent with both incisions. Bronchopneumonia occurred only after M in five patients (1 C, 4 COPD). In contrast with the control patients in whom no difference was found between T and M incisions, the FEV1 of COPD patients was significantly less impaired with T than with M incisions (p less than 0.005 on D2 and p less than 0.05 on D5). VC decreased similarly with both incisions on D2 but on D5 the improvement was less with M (p less than 0.005). Changes in AaPO2 were more marked on D2 and D5 for the COPD patients with M incisions. We conclude that (1) in patients with chronic obstructive pulmonary disease, laparotomy with a transverse incision was associated with better postoperative lung function and fewer pulmonary complications; (2) in patients without pulmonary disease, midline and transverse incisions were equivalent. PMID- 2933438 TI - Prophylactic antibiotic coverage in patients with total arthroplasty: current practice. AB - The need for prophylactic antibiotic coverage before dental treatment to prevent late prosthetic joint infection has not been established. Most orthopedic surgeons who responded to the survey thought that no relationship existed between dentally induced transient bacteremias and prosthetic joint infections, but a majority of these respondents recommended antibiotic prophylaxis anyway. The current literature discloses few late prosthetic joint infections that can be attributed to the transient bacteremia expected to occur after dental treatment. Most of the respondents who recommended prophylactic antibiotics, preferred a cephalosporin. The use of this antibiotic may not be indicated because transient bacteremias that occur after dental treatment primarily are streptococcal and are of oral origin. The preferred drug for the control of oral organisms remains penicillin. Penicillin also remains the antibiotic recommended by the American Heart Association as the preferred prophylaxis against infective endocarditis secondary to dental treatment. Before any definitive statement concerning the prevention of prosthetic joint infections occurring after dentally induced transient bacteremias can be made, additional research needs to be conducted to determine the extent of the relationship and to determine the antibiotic most effective in controlling the specific bacteria involved. Currently, we recommend that dental practitioners who provide treatment to patients with arthroplasty consult with and follow the recommendations of the patient's orthopedic surgeon regarding antibiotic prophylaxis. However, we believe that the orthopedic and dental professions need to form a joint committee to examine and evaluate the current data. After this evaluation, a joint statement that concerns the relationship of and recommendations for the prevention of dentally induced bacteremias and joint infections should be issued. PMID- 2933439 TI - Dental management of patients with hereditary angioedema: report of case. AB - Dental management and treatment of a patient with hereditary angioedema can be accomplished safely and satisfactorily in an outpatient setting by a dentist in collaboration with a physician. However, as acute attacks can occur as a complication of treatment, we recommend that dental treatment be provided in a hospital environment with adequate medical emergency resources. PMID- 2933440 TI - The continued in vivo evaluation of the wear of restorative resins. AB - This study reports on the 3-year results of a method designed to measure the in vivo wear rates of resin systems in denture teeth. Adaptic and Profile showed the most amounts of wear, followed by Finesse, Miradapt, and Isopast. The least amounts of wear were seen with Isosit and Silar. The similarity to the magnitudes of wear reported in other studies suggests the appropriateness of using this technique. PMID- 2933441 TI - Clinical and angiographic assessment 6 months after double vessel percutaneous coronary angioplasty. AB - Percutaneous transluminal coronary angioplasty is an accepted treatment for selected patients with single vessel disease but has not been rigorously evaluated in patients with double vessel disease. Among 769 patients undergoing transluminal coronary angioplasty between 1980 and 1984, 74 with double vessel stenosis of 50% or more underwent double vessel coronary angioplasty. Primary success was obtained for both lesions in 63 patients (85%), for one lesion in 11 patients (15%) and for 137 (93%) of 148 segments overall. Except for myocardial infarction in one patient, no serious complication occurred. Before coronary angioplasty, 15 patients had unstable angina, 14 had Canadian Cardiovascular Society class III and 32 class I to II effort angina and only 2 were asymptomatic. Six months after coronary angioplasty, 27 were asymptomatic, 27 had class I to II and 5 had class III effort angina and 2 had sustained an episode of unstable angina. During the follow-up study, two patients had an infarction and one had coronary artery bypass surgery. Coronary arteriography was performed at a mean of 5.5 +/- 2.1 months after coronary angioplasty in all but three patients. Restenosis was found in 30 (23%) of 132 segments with angiographic control. Restenosis was present in one vessel in 17 patients and in both vessels in 4; 40 patients (66%) had no restenosis. Of the 34 patients with definite or probable angina, 50% had restenosis and 19% of patients with restenosis were symptom free.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2933442 TI - The diversity of reaginic immune responses to platinum and palladium metallic salts. AB - As part of a National Institute for Occupational Safety and Health health hazards evaluation, workers employed in a precious metal refinery exposed to platinum (Pt), palladium (Pd), and other group VIII metallic salts were evaluated for direct skin test sensitivity to Pt. Current (107) and former (30) workers who quit or were discharged because of Pt-related health problems were prick tested with ammonium hexachloroplatinate ([NH4]2 PtCl6). Of the 107 currently exposed workers, 15 (14%) exhibited positive skin tests, as indexed by immediate reactivity at a dose of 10(-3) gm/ml or less. Eight (27%) of the 30 former workers no longer exposed to Pt also demonstrated positive Pt skin tests. Sera obtained from the workers were assessed for transferable antibodies to Pt and Pd salts by monkey passive cutaneous anaphylaxis. In addition, Pt-specific antibodies were evaluated by RAST. Results of these studies suggested that short- and long-term passive cutaneous anaphylaxis immune responses occur after exposure to both Pt and Pd compounds. Results of RAST analysis for Pt-specific antibodies indicated that significantly higher (p less than 0.001) levels were present in the sera of skin test-positive workers as compared to control sera from Pt exposed, skin test-negative workers or nonexposed control subjects. Evidence was also obtained that Pt or Pt-protein adducts present in the sera of exposed workers may compete for IgE-binding sites in the RAST assay. The specificity of the Pt-specific RAST system was proved by inhibition experiments. PMID- 2933443 TI - The adrenergic innervation of pulmonary vasculature in the normal and pulmonary hypertensive rat. AB - It would appear that susceptibility to chronic proliferative pulmonary hypertension in response to chronic alveolar hypoxia is most severe in species in which adrenergic innervation of pulmonary arteries is reduced or lacking. Intrapulmonary arteries of the rat have been reported to lack adrenergic innervation by some workers but not others. Since the rat develops severe proliferative pulmonary hypertension in response to prolonged alveolar hypoxia, the different divisions of the lung vasculature of Sprague-Dawley rats were thoroughly examined to determine the presence or absence of an adrenergic innervation. The degree of innervation in normal rats was compared with that of rats developing pulmonary hypertension. Both in normal and experimental pulmonary hypertensive rats the pulmonary arteries, all their branches and the small pulmonary veins with a smooth muscle media were found to be devoid of adrenergic innervation. In contrast, the cardiac-like muscle in the media of large pulmonary veins, the bronchial arteries and the vasa vasorum of larger vessels were richly innervated by adrenergic nerves. Thus the increase in medial smooth muscle which occurs in pulmonary arteries during chronic alveolar hypoxia is independent of a pre-existing adrenergic innervation or of such an innervation newly derived from that of adjacent vessels or structures. This is in contrast to systemic vessels where it has been suggested that increased adrenergic activity and density of innervation may augment hypertrophy of the media in hypertensive animals. Adrenergic nerves are suggested to have a protective action on pulmonary vessels. PMID- 2933444 TI - A quantitative method of determining the pneumatic ankle tourniquet setting. AB - Pneumatic ankle tourniquets are currently used in podiatry for maintaining hemostasis during foot surgery. The literature is limited concerning the safest pressure to use with this device. This study was undertaken to develop a simple and reliable method of deriving a proper pressure setting that would be safe and efficacious. Using a Doppler stethoscope, the minimum effective tourniquet pressure was established on 54 limbs from 35 patients undergoing foot surgery at our institution. The average pressure needed to obtain a "bloodless field" was 218.6 +/- 34.6 mm. Hg. However, in the younger, normotensive patients the average pressure utilized was 203.9 +/- 22.3 mm. Hg. The lower pressures used were felt to be safer and better tolerated by the patients. The authors concluded that the minimum effective pressure should be determined for each patient preoperatively and the routine use of a maximum safe pressure of 250 mm. Hg should be discouraged. PMID- 2933446 TI - [Diagnosis of a trisomy 21 in the first pregnancy trimester. Value of trophoblast sampling]. AB - The authors report a diagnosis of trisomy 21 in the 11th week following the last menstrual period in a patient of 40 years of age. This was made by chorion villi aspiration and direct cytogenetic examination. PMID- 2933447 TI - Epidemiological model of acute bacterial and viral diarrhoeal diseases. PMID- 2933445 TI - A case of mucinous cystadenocarcinoma of the ovary associated with virilization: pre and post-operative steroid plasma levels. AB - A premenopausal woman with a mucinous carcinoma of one ovary, and a mucinous adenoma of the other, together with secondary virilization, is reported. Preoperative levels of androstenedione, testosterone and dehydroepiandrosterone sulphate were high, suggesting the presence of a virilizing tumor. Preoperative plasma estrone (E1), but not estradiol (E2), was elevated along with inversion of the E2/E1 ratio, suggesting a peripheral origin of the estrogens. FSH and LH plasma concentrations were low. After bilateral ovariectomy, levels of all steroids measured significantly decreased and gonadotropins rose to the postmenopausal range. PMID- 2933448 TI - HLA A1-B8-DR3 and suppressor cell function in first-degree relatives of patients with autoimmune chronic active hepatitis. AB - The relationship between suppressor T cell function and the inheritance of the A1, B8, DR3 haplotype was studied in 17 healthy, first-degree relatives of patients with autoimmune chronic active hepatitis. A marked defect in suppressor cell function was found significantly more often in A1, B8, DR3-positive relatives (5 of 7) compared with those who were A1, B8, DR3-negative (1 of 10; P = 0.017). Less marked abnormalities were also found in the A1, B8, DR3-negative relatives compared with A1, B8, DR3-negative control subjects. The results indicate that the defects in suppressor cell function in patients with untreated chronic active hepatitis result from the inheritance of genetic factors linked to the major histocompatibility complex and other gene loci and are not secondary to hepatic inflammation. PMID- 2933449 TI - Sudden death secondary to anomalous origin of the right pulmonary artery from the aorta. PMID- 2933450 TI - Antibody-complement-mediated cytotoxicity is enhanced by ribosome-inactivating proteins. AB - The antibody-mediated cytotoxicity of complement can be increased by the ribosome inactivating proteins gelonin and PAP-S. Treatment of human lymphoid cells that express CALLA with an anti-CALLA monoclonal antibody, J5, and then with rabbit complement, leaves about 6% of the cells alive. The same treatment in the presence of a sublethal concentration of gelonin or PAP-S leaves only about 0.02 and 0.3% of the cells alive respectively. This synergistic effect has potential implications for the in vitro elimination of malignant cells or of immunocompetent cells from bone marrow before its transplantation. PMID- 2933451 TI - Modulation of suppressor T cell induction with gamma-interferon. AB - The ability of antigen-coupled splenic adherent cells to induce suppressor T cells (Ts) is dependent on the presence of I-J determinants on antigen-presenting cells. After 4 days of in vitro culture, antigen-coupled adherent cells lose the capacity to induce Ts. Supernatants from Con A-stimulated lymphocyte cultures and purified interferon-gamma can sustain accessory function for the induction of Ts. Furthermore, after in vitro culture of splenic adherent cells, there is an apparent correlation between the loss of I-A determinants and the decrease in I-J restricted Ts induction. Stimulation of Ia expression with interferon-gamma results in a simultaneous increase in the ability to induce Ts. Finally, elimination of I-A-bearing splenic adherent cells with antibody + C eliminates I J-restricted Ts induction. The combined data imply a co-regulation of I-A and I-J on the antigen-presenting cells involved in the induction of both the Ts1 and Ts3 suppressor T cell subsets. PMID- 2933452 TI - Migration of natural suppressor cells from bone marrow to peritoneal cavity by live BCG. AB - Delayed-type hypersensitivity (DTH) responses were suppressed in mice inoculated with bone marrow cells from mice that had been injected with 10(8) colony-forming units (CFU) of live BCG. Upon analysis of this DTH-suppression by the use of a macrophage migration inhibition (MI) assay, the in vitro correlate of DTH, suppressor macrophages in the peritoneal cavity were found to play an important role in DTH suppression. However, neither suppression of DTH nor production of suppressor macrophages was observed in mice inoculated with bone marrow cells from mice that had been injected with methotrexate (MTX), a folic acid antagonist, and 10(8) CFU of live BCG. Moreover, suppressor cells against the MI activity of peritoneal exudate cells from BCG cell wall-immunized mice existed in bone marrow cells from normal mice, natural suppressor (NS) cells, and they were sensitive to MTX. In addition, these NS cells phagocytized carbonyl iron particles, were adherent to Sephadex G-10, and had Fc receptors, but they had no B or T cell markers, suggesting that these cells belonged to a macrophage compartment. From this evidence, we hypothesized that the origin of suppressor macrophages in the peritoneal cavity induced by live BCG injection was MTX sensitive NS cells in bone marrow, and that these NS cells were stimulated by a small dose of live BCG trapped in bone marrow after i.v. injection of a high dose of live BCG and migrated from bone marrow to the peritoneal cavity. PMID- 2933453 TI - Dietary fat and immune function. II. Effects on immune complex nephritis in (NZB x NZW)F1 mice. AB - (NZB x NZW)F1 mice initiated on fat restriction at weanling were significantly protected from the development of immune complex glomerulonephritis. Whereas the mice on high-fat intake demonstrated immune depositions both in capillary walls and mesangial areas in a diffuse granular pattern, those on a low-fat diet with caloric content similar to the high-fat diets exhibited mesangial confinement of the depositions of immunoglobulins, complement, and retroviral gp70. In association with these divergent patterns of immune deposition, the mice on high fat diets had evidence of extensive diffuse cellular proliferation, wire loop lesion, and sclerosis in the glomeruli. In contrast, most of the mice on the low fat diet showed only mesangial cell and matrix proliferations. In addition, the group of mice fed high saturated fat showed more severe glomerular pathology as compared to those fed high unsaturated fat. Paradoxically, levels of circulating immune complexes (as measured by the polyethylene glycol precipitation technique) in the high saturated fat group were low and did not correlate with the findings by light and immunofluorescence microscopy. These findings suggest that dietary fat restriction can serve as either a prophylactic or effective therapeutic approach to murine lupus nephritis. PMID- 2933454 TI - T cell unresponsiveness to the mitogenic activity of OKT3 antibody results from a deficiency of monocyte Fc gamma receptors for murine IgG2a and inability to cross link the T3-Ti complex. AB - We recently identified defective monocyte accessory function as the cause of T cell unresponsiveness to the mitogenic activity of OKT3 antibody in cultures of peripheral blood mononuclear cells (PBMC) from five healthy subjects, members of one family. We now report that the underlying abnormality in nonresponders is at the level of monocyte Fc gamma receptors for murine IgG2a. T cell unresponsiveness was not restricted to the signal provided by OKT3 but occurred also for two other anti-T3 antibodies of the IgG2a subclass, in contrast to a normal proliferative response to IgG1 anti-T3 antibodies in one of the OKT3 nonresponders. By using cytofluorography, we found that monocytes from responders but not from nonresponders bound OKT3-FITC to their membrane. The binding could be blocked by mouse IgG2a and by human IgG, but not by mouse IgG1 nor by serum albumin. The data suggest that, through specific Fc gamma receptors for murine IgG2a, monocytes bind the Fc portion of OKT3 during T cell activation. The function of this Fc gamma receptor binding was further studied by culturing PBMC from nonresponders on plates coated with affinity-purified goat anti-mouse IgG antibodies as a substitute for monocyte Fc gamma receptors. The addition of OKT3 to nonresponder PBMC, cultured on such plates, resulted in T cell activation, as evidenced by thymidine incorporation, IL 2 production, and expression of IL 2 receptors. Soluble anti-mouse IgG was not able to substitute for monocyte Fc gamma receptors. The results demonstrate the existence of polymorphism in monocyte Fc gamma receptors for murine IgG2a. They also substantiate that an essential helper function of monocytes in T cell activation by anti-T3 is to provide a matrix for multimeric binding of the Fc portion of the anti-T3 antibodies in order to cross-link T3 molecules. PMID- 2933455 TI - The effect of bone marrow depletion on prostaglandin E-producing suppressor macrophages in mouse spleen. AB - The i.p. injection of Corynebacterium parvum (CP) into CBA/J mice effected increases in macrophage colony-forming cells (M-CFC) when spleen cells were cultured with L cell culture filtrate as a source of colony-stimulating factor. Significant increases in phagocytic macrophages (M phi) with Fc receptors for IgG2a and IgG2b immune complexes were additionally noted among the spleen cells in these mice. These M phi effectively inhibited Con A-induced lymphocyte proliferation, probably reflecting a 10-fold increase above normal controls in prostaglandin E to 47 ng/3 X 10(6) spleen cells/ml. To determine whether the suppressor M phi are immediate derivatives of splenic M-CFC, we tried to induce suppressor M phi by the injection of CP into mice depleted of bone marrow M-CFC by the earlier administration of the bone-seeking isotope, 89Sr. This procedure reduced M-CFC in the bone marrow to less than 1% of normal for more than 30 days. Monocytes in the blood fell to 5% of normal by day 10 and were 30% on day 30. Levels of resident peritoneal M phi showed relatively little change in this period. By contrast, splenic M-CFC increased to 20-fold higher than the "cold" 88Sr controls. CP-induced suppressor M phi activity, however, was sharply reduced in 89Sr marrow-depleted mice on day 10, despite the striking increase in M-CFC. There was a threefold increase in the number of phagocytic M phi binding IgG2a immune complexes, with no significant increase in IgG2b binding M phi. The kinetics of recovery of suppressor M phi activity showed that on days 20, 30, and 50 after 89Sr injection the activities reached 20%, 30%, and 70% of the "cold" control, respectively, and correlated with the recovery of significant levels of M-CFC in the bone marrow. Taken together, these observations suggest that splenic M-CFC are not an immediate source of PGE-suppressor M phi in vivo. It appears more likely that the CP-inducible suppressor M phi, in particular, originate from radiosensitive bone marrow cells or require for differentiation a microenvironment provided by bone marrow cells. The data also suggest that the expression of the Fc gamma 2b receptor and of suppressor activity by CP-induced splenic M phi are related phenomena. PMID- 2933456 TI - Cytokine production and utilization by the motheaten mouse. AB - Splenocytes from the motheaten mouse, after stimulation with alloantigen, lack the ability to utilize exogenous interleukin 1 (IL 1) or interleukin 2 (IL 2), express receptors for IL 2, or produce (IL 2). However, in contrast to other models of autoimmunity and immunodeficiency, after mitogen stimulation, motheaten splenocytes produced as much IL 1 or IL 2 as their normal littermates. In addition, these splenocytes expressed functional IL 2 receptors in the same quantity as normal littermate or wild-type splenocytes. Furthermore, motheaten thymocytes and splenocytes, like their normal littermates, respond synergistically to IL 1 on co-stimulation with mitogen, suggesting expression of an IL 1 receptor. Thus, motheaten mouse splenocytes are unable to utilize an antigen-delivered signal and convert it into cytokine production or IL 2 receptor expression. If the antigen signal is bypassed with mitogen, cytokine production and receptor expression appear normal. PMID- 2933457 TI - Regulation of T cell proliferation by cloned interferon-alpha mediated by Leu-11b positive cells. AB - The autologous T lymphocyte proliferative response (AMLR) induced by a B lymphocyte-enriched non-T, nonadherent cell population (NT, NAC) and by a macrophage-enriched population were both suppressed by the addition of a cloned interferon-alpha (IFN-alpha Con1) directly to the cultures. Preincubation of the stimulating NT, NAC with IFN-alpha Con1 resulted in comparable suppression. In contrast, preincubation of the macrophages with IFN-alpha Con1 resulted in significant augmentation of T cell proliferation. Depletion of Leu-11b-positive cells from the NT, NAC exposed to IFN-alpha Con1 restored the autologous T cell response. Addition of IFN-alpha Con1 activated Leu-11b-positive cells, isolated from the NT, NAC population, was suppressive of the AMLR. Although NK cytotoxicity was irradiation sensitive, suppression of the AMLR by IFN-alpha Con1 activated NT, NAC was resistant, suggesting that different subsets of cells or mechanisms by the same cells may have been responsible. These observations may offer insights into the potential role of cells with the NK phenotype, Leu-11b, and IFN in contributing to immuno-regulatory changes observed in clinical states associated with elevated concentrations of IFN. PMID- 2933458 TI - Characterization of human IgG Fc receptors. AB - A murine monoclonal antibody, KuFc79, has been developed that reacts with human IgG Fc receptors on monocytes, B lymphocytes, and granulocytes. The specificity of KuFc79 for Fc receptors was demonstrated by the ability of Fab fragments to block Fc-mediated phagocytosis by monocytes. This finding was further substantiated by the decrease of KuFc79 binding to monocytes and granulocytes (58 and 70%, respectively) after modulation of surface IgG receptors with aggregated IgG. In addition, Fab KuFc79-conjugated Sepharose was used to isolate functional IgG Fc-binding molecules from soluble extracts of the human monocyte-like cell line U937. By immunoprecipitation, it was further shown that KuFc79 immunoprecipitated molecules of 42,000 and 70,000 daltons from U937 and a human lymphoblastoid cell line, SB. A lower m.w. species of approximately 33,000 was also precipitable from granulocytes. Extensive microheterogeneity of these molecules was noted by isoelectric focusing, which appears to be due to differential sialation. PMID- 2933459 TI - Influence of genetically inherited complement deficiencies on humoral immune response in guinea pigs. AB - To assess the role of complement in the induction of the humoral immune response, we studied the antibody response of guinea pigs genetically deficient in the second component of the classical complement pathway (C2D-GP) to bacteriophage phi X 174--a T cell-dependent antigen--in comparison with normal guinea pigs and C4D-GP, for which a disturbance in induction of antibody response has been described. We were able to establish a clear dose-response relationship: with low doses of antigen (1 X 10(9) PFU/kg), the antibody response of both complement deficient strains was grossly impaired as compared with normal guinea pigs. After primary immunization, the peak antibody titer was diminished (1 log10) and declined rapidly; after secondary immunization, the diminution became even more distinct. Both complement-deficient strains had unusual secondary antibody responses almost identical to their primary ones, and amplification of antibody titer, as well as regular isotype switch from IgM to IgG, was absent. By increasing the antigen dose (2 X 10(9) PFU/kg), the antibody responses of the complement-deficient guinea pigs tend to normalize, and when high doses of antigen (1 X 10(10) PFU/kg) were used, the behavior of the complement-deficient animals was nearly indistinguishable from that of normal animals. Partial restoration of the immune response was seen when substituting the genetic complement deficiency by giving serum as source of the missing complement component. The important contribution of the C2 deficiency is given by the now compelling evidence that it is not the missing individual component itself, but rather the common block in sequential activation of C3 via the classical pathway in both complement deficiencies, that is responsible for the impaired humoral immune response, especially at low antigen doses. We therefore postulate that an intact classical pathway contributes to reaching a normal humoral immune response. PMID- 2933460 TI - Differences in "host infiltrates" among lymphoma patients treated with anti idiotype antibodies: correlation with treatment response. AB - To correlate treatment responses with numbers and types of "host cell infiltrates," lymphoid tissues from 10 patients with low-grade B cell malignancies were stained before, during, and after anti-idiotype therapy with a panel of monoclonal antibodies applied to frozen sections. Tissue penetration by the anti-idiotype antibodies was confirmed in five patients by these immunoperoxidase methods. Large numbers of phenotypic T helper cells were the main component of the "host infiltrate" in most patients. Two patients showed a complete and a near-complete clinical remission, four others had partial responses, and four did not respond to therapy. The two patients that developed clinical remission demonstrated the largest number of T cells, T helper cells, TAC+ cells, Leu-7+ cells, and in general the smallest number of proliferating cells as measured by the Ki-67 antibody. Other major differences in host cells were not evident among the patients. These preliminary data suggest that the type and amount of "host infiltrate" in low-grade B cell lymphomas may predict which patients will respond to anti-idiotype therapy. PMID- 2933461 TI - The immunobiology of T cell responses to Mls-locus-disparate stimulator cells. III. Helper and cytolytic functions of cloned, Mls-reactive T cell lines. AB - Mls-specific T cell clones derived by limiting dilution were tested for cytotoxic activity in a lectin-dependent 51Cr-release assay. All the T cell clones tested were cytotoxic in such an assay in apparent contrast to previous reports. However, only those target cells sensitive to cytolysis by other L3T4a+ cytolytic T cells were killed by Mls-specific T cell clones in short term 51Cr-release assays, possibly explaining this discrepancy. All the T cell clones tested were L3T4a+, Lyt-2- and stimulated B cells from Mlsa,d strains of mice to proliferate and secrete immunoglobulin. Furthermore, lysis of innocent bystander targets was observed when the T cells were stimulated with Mls-disparate stimulator cells. These results are consistent with those obtained with L3T4a+ T cells specific for protein antigen:self Ia and that express cytotoxic potential. PMID- 2933462 TI - The interferon-gamma receptor in human monocytes is different from the one in nonhematopoietic cells. AB - The receptor for interferon-gamma (IFN-gamma) on peripheral blood monocytes was characterized and was compared with that of human WISH cells. 125I-IFN-gamma was specifically bound to both cells; however, different binding characteristics were obtained. In the case of monocytes, Scatchard analysis gave an upward concave dependency curve, indicating either multiple binding sites or a negative cooperativity among the binding sites. In contrast, a linear Scatchard plot was obtained for the binding in WISH cells. Competition studies gave even more striking differences. Acid-treated IFN-gamma (95% inactivated) effectively competed with 125I-IFN-gamma for binding to the receptor on WISH cells, but not on monocytes. The significance of these differences was evaluated by analyzing the various biological activities of IFN-gamma in these two cell types. IFN-gamma was found to induce an antiviral state in WISH cells, but not in monocytes. Acid treated IFN-gamma was found to be almost as active as IFN-gamma itself in inducing HLA-DR in WISH cells, but was almost completely inactive as an HLA-DR inducer in monocytes. It is proposed that these variations in biological activity stem from the presence of different receptors for IFN-gamma in monocytes and in WISH cells. Moreover it is suggested that the immunoregulatory functions of IFN gamma in monocytes are related to the presence of a distinct IFN-gamma receptor in these cells. PMID- 2933463 TI - A mitogenic factor for endothelial cells obtained from mouse secondary mixed leukocyte cultures. AB - Supernatants from secondary mixed leukocyte cultures (MLC) are capable of stimulating both endothelial cell proliferation and endothelial cell chemokinesis. The proliferation factor(s) has been subject to further biochemical characterization. At least one factor is precipitable by 30% ammonium sulfate, a procedure that separates this factor from the chemokinesis-inducing factor(s) and most other growth-stimulating lymphokines. The partially purified lymphokine preparation can stimulate growth of microvascular endothelial cells, yet fails to induce proliferation of large vessel endothelium and a variety of other cell types. Addition of indomethacin to the MLC medium leads to an increase in endothelial cell mitogenic activity. Chromatography on S-200 Sephacryl suggests a m.w. greater than 200,000 when eluted in isotonic saline, whereas the apparent m.w. is less than 30,000 when the material is eluted from the same column with 0.5 M ammonium acetate. The proliferative activity is stable to acid (pH 2) but not to heat treatment at 50 degrees C. Although the factor is resistant to trypsin digestion, it is sensitive to digestion with pronase, suggesting that it is a protein. The potential importance of endothelial cell-specific lymphokines in the vascular responses accompanying inflammation and disease-associated neovascular reactions is discussed. PMID- 2933464 TI - Effect of selective T cell depletion of host and/or donor bone marrow on lymphopoietic repopulation, tolerance, and graft-vs-host disease in mixed allogeneic chimeras (B10 + B10.D2----B10). AB - Reconstitution of lethally irradiated mice with a mixture of T cell-depleted syngeneic plus T cell-depleted allogeneic bone marrow (B10 + B10.D2----B10) leads to the induction of mixed lymphopoietic chimerism, excellent survivals, specific in vivo transplantation tolerance to subsequent donor strain skin grafts, and specific in vitro unresponsiveness to allogeneic donor lymphoid elements as assessed by mixed lymphocyte reaction (MLR) proliferative and cell-mediated lympholysis (CML) cytotoxicity assays. When B10 recipient mice received mixed marrow inocula in which the syngeneic component had not been T cell depleted, whether or not the allogeneic donor marrow was treated, they repopulated exclusively with host-type cells, promptly rejected donor-type skin allografts, and were reactive in vitro to the allogeneic donor by CML and MLR assays. In contrast, T cell depletion of the syngeneic component of the mixed marrow inocula resulted in specific acceptance of allogeneic donor strain skin grafts, whether or not the allogeneic bone marrow was T cell depleted. Such animals were specifically unreactive to allogeneic donor lymphoid elements in vitro by CML and MLR, but were reactive to third party. When both the syngeneic and allogeneic marrow were T cell depleted, variable percentages of host- and donor-type lymphoid elements were detected in the mixed reconstituted host. When only the syngeneic bone marrow was T cell depleted, animals repopulated exclusively with donor-type cells. Although these animals had detectable in vitro anti-host (B10) reactivity by CML and MLR and reconstituted as fully allogeneic chimeras, they exhibited excellent survival and had no in vivo evidence for graft-vs-host disease. In addition, experiments in which untreated donor spleen cells were added to the inocula in this last group suggest that the presence of T cell depleted syngeneic bone marrow cells diminishes graft-vs-host disease and the mortality from it. This system may be helpful as a model for the study of alloresistance and for the identification of syngeneic cell phenotypes, which when present prevent engraftment of allogeneic marrow. PMID- 2933465 TI - In vitro T cell-mediated killing of Pseudomonas aeruginosa. III. The role of suppressor T cells in nonresponder mice. AB - T lymphocytes from immune BALB/c mice can adoptively transfer protection against infection with the extracellular Gram-negative bacterium Pseudomonas aeruginosa to nonimmune recipients, and in vitro, immune T cells are able to kill these bacteria. Earlier studies indicated that this killing is mediated by a bactericidal lymphokine. The current studies demonstrate that T cells from immunized CB.20 mice, a strain congenic with BALB/c, fail to kill Pseudomonas aeruginosa in vitro. This nonresponsiveness is attributable to the activity of suppressor T cells of the Lyt-1-, 2,3+, I-J+ phenotype. CB.20 mice are known to differ from BALB/c mice only at a single locus, which includes the Igh-1 allotype CH genes. These results suggest a critical role for this locus or closely linked genes in the control of T cell killing of this extracellular bacterium. PMID- 2933466 TI - Two independent pathways of helper activity provided by a single T cell clone. AB - Data presented in this paper demonstrate the existence of two separate pathways by which a single T cell clone can induce B cell differentiation. With the use of high doses of antigen, a T cell clone can induce a primary antibody response in unprimed B cells. With the use of low doses of antigen, the same T cell clone can induce an immunoglobulin (Ig)G response in primed B cells. The primary response is accompanied by T cell proliferation and lymphokine production (interleukin 2, B cell growth factor, B cell differentiation factor for immunoglobulin M, and B cell differentiation factor for immunoglobulin G). The secondary response does not require proliferation and occurs independently of detectable lymphokine production. Variants of the wild type T cell helper clone have been isolated. One variant can provide help to unprimed B cells when high doses of antigen are used. This variant cannot provide help to primed B cells when low doses of antigen are used, nor can it provide help to CBA/N "xid" B cells at any antigen concentration tested. Additional variants have been isolated that proliferate on antigen-pulsed presenting cells, but fail to secrete detectable lymphokines and do not induce B cell differentiation. These results suggest that a single T cell helper clone has multiple functional activities that can be independently expressed. PMID- 2933467 TI - A microtiter plate assay for detecting IgE-binding molecules and cells bearing Fc receptors for IgE. AB - A microtiter plate assay is described for detecting cells bearing Fc receptors for IgE (Fc epsilon receptors) and for assaying IgE-binding molecules. Cells are bound specifically to IgE-coated wells of microtiter plates, and the bound cells are enumerated in a quantitative colorimetric assay. IgE-binding molecules and monoclonal antibodies are assayed as inhibitors of the IgE-dependent cell binding. Major advantages of the plate assay compared to rosetting assays are its ability to accommodate many test samples for replicates and titrations and the ease with which results are read out. The versatility of the assay is discussed with respect to detecting other immunoglobulin Fc receptor-bearing cells. PMID- 2933468 TI - Assay and characterization of IgG binding to endodermal cells of the fetal rabbit yolk sac membrane. AB - The transfer of passive immunity in the rabbit is mediated by the fetal yolk sac membrane (YSM) and is initiated by the specific binding of IgG to receptors on the microvillar surface of the endoderm from the YSM. This report describes the preparation of suspensions of endodermal absorptive cells of the YSM and their use in equilibrium binding experiments to characterize the nature of the binding reaction. Equilibrium binding is achieved in 4 h at 4 degrees C. The system is more rapid than, affords greater reproducibility of binding data than, and utilizes only about 1/10 the amount of YSM and ligand as the YSM disc assay system (Tsay and Schlamowitz, 1975) used previously. A Scatchard plot of the binding data over a wide range of IgG concentration was non-linear implying the presence of at least 2 binding elements. Apparent binding constant values for the stronger and weaker binding components in this population differed by about 50 fold. For the weaker binding system, binding decreased when temperature was increased indicating that the reaction was not entropy-driven (i.e., dominated by hydrophobic 'forces') and that ionic interactions might be a major factor. At low ionic strengths the measurement of specific binding was complicated by the effects of secondary ionic interactions. At physiological ionic strength the binding of IgG was species-specific. PMID- 2933469 TI - A new competitive assay for monoclonal antibodies against phi X174 single stranded DNA. AB - A new method using L-lysine-conjugated Sepharose 4B as a matrix for coupling competitors is described for analysis of the specificity of monoclonal antibodies against single stranded DNA. In this assay, competitor-coupled Sepharose 4B is first incubated with an antibody, and then the competitor is removed (together with the antibody that is bound to it) by low-speed centrifugation of the reaction mixture. The supernatant containing only unreacted antibody is then analysed by an enzyme-linked immunosorbent assay. The method is simple and does not use radioactive materials. Moreover it is not subject to the data fluctuation that is caused by the binding of competitors to microplates in a commonly used enzyme-linked immunosorbent assay employing high concentrations of competitors. PMID- 2933470 TI - The in vitro effect of retinol on human gingival epithelium. II. Modulation of Langerhans cell markers and interleukin-1 production. AB - The in vitro influence of retinol on the markers of gingival Langerhans cells (LC) was investigated using an organ culture system. Retinol at a dose of 5 micrograms/ml produced an increase in the density of T6-positive cells within the epithelium which peaked during the first 24 h of culture. LC HLA-DR and ATPase markers were maintained for the same period, while all markers were depressed after 72 h. These effects were not seen in explants cultured in conventional or alcohol-enriched media, in which all markers were lost in an exponential fashion. In addition to modulation of LC markers, retinol treatment also prolonged the expression of HLA-DR antigens by gingival keratinocytes. These findings, together with the augmented production of interleukin-1-like activity by retinol-treated gingival organ cultures suggest that low doses of retinol may alter immune reactions within epithelia via stimulation of both keratinocytes and LC. PMID- 2933471 TI - Alterations in the immune response of nonresponders to the hepatitis B vaccine. AB - The phenotypic characteristics of peripheral blood lymphocytes (PBLs) from responders and nonresponders to hepatitis B (HB) vaccine and their response to pokeweed mitogen (PWM) stimulation in vitro were compared. The nonresponders had significantly higher absolute numbers and percentages of T11+, HNK-1+, and T8+ lymphocytes. Also, after PWM stimulation, PBLs from HB-vaccine nonresponders had impaired IgG and IgM production and failed to produce antibodies to HB surface antigen in vitro. These findings suggest that healthy individuals who fail to produce such antibodies have a higher population of suppressor lymphocytes that alters their normal immune response to HB vaccination. PMID- 2933472 TI - Abnormal immunologic response to hepatitis B in two brothers--a genetic effect? PMID- 2933473 TI - Carriage of oral Candida albicans associated with a high number of circulating suppressor T lymphocytes. PMID- 2933474 TI - [Cardiovascular hemodynamics in patients with essential hypertension during multi stage exercise]. AB - We investigated cardiovascular hemodynamics in patients with essential hypertension at rest and during exercise. Eight patients with borderline hypertension (Group B), 18 patients with sustained hypertension, and 10 normotensive subjects (Group N) were studied. Patients with sustained hypertension were categorized in two groups; 10 patients without cardiac hypertrophy (Group NH), and eight patients with cardiac hypertrophy (Group HH). To assess the cardiovascular hemodynamics, M-mode echocardiograms, electrocardiograms and carotid pulses were recorded during multistage exercise using a supine bicycle ergometer. Blood pressure was measured simultaneously by the cuff method. At rest, isovolumic relaxation times (IRT) in Groups NH and HH were significantly prolonged as compared with that of Group N. The IRT of Group HH was significantly prolonged as compared with that of Group NH (Group N: 0.06 +/- 0.01 sec, Group B: 0.07 +/- 0.01 sec, Group NH: 0.08 +/- 0.02 sec, Group HH: 0.09 +/- 0.01 sec, respectively). Only the atrial filling fraction of Group HH was significantly increased over that of Group N (Group N: 25.6 +/- 12.1%, Group B; 30.0 +/- 8.1%, Group NH: 27.9 +/- 11.3%, and Group HH: 41.4 +/- 13.1%, respectively). The total peripheral vascular resistance (TPR) in Groups NH and HH was significantly increased over that of Group N (Group N: 1600 +/- 224 dyne/sec/cm-5, Group B: 1704 +/- 465 dyne/sec/cm-5, Group NH: 2370 +/- 608 dyne/sec/cm-5, and Group HH: 3290 +/- 1598 dyne/sec/cm-5, respectively). There was no significant difference in the cardiac index, ejection fraction or heart rate among all groups at rest and during exercise. However, the difference between TPR at rest and TPR at a load of 75 watt (delta TPR) was increased in Groups NH and Group HH over Group N (Group N: 558 +/- 166 dyne/sec/cm-5, Group B: 614 +/- 336 dyne/sec/cm-5, Group NH: 883 +/- 415 dyne/sec/cm-5, and Group HH: 1306 +/- 774 dyne/sec/cm-5, respectively). From these findings, we concluded that there is early diastolic left ventricular dysfunction in Groups NH and HH, and that the degree is more distinct in Group HH. It seems that systolic left ventricular function of both groups is normal during moderate exercise loads, and marked reduction of the TPR in both groups during exercise may be caused by marked peripheral vascular dilatation. PMID- 2933476 TI - [The functions of salivary neutrophils]. PMID- 2933475 TI - [Two-dimensional echo-Doppler technic for evaluating dissecting aneurysms using the paravertebral approach]. AB - Cross-sectional echocardiography facilitates recognizing dissecting aortic aneurysms, but the diagnosis of abnormalities of the descending aorta in the retrocardiac portion is difficult. We prospectively designed to assess the usefulness of a new echocardiographic technique in defining the retrocardiac descending thoracic aorta in its long and short axes. Two patients with dissecting aneurysms involving the retrocardiac descending aorta were studied in the 90 degrees right lateral position using a Toshiba SSH-11A or SSH-40A cross sectional echocardiographic apparatus. The transducer was positioned in the third or fourth intercostal space closely to the left of the thoracic vertebrae, and the ultrasonic beam was directed toward the retrocardiac descending aorta from the patient's back. The descending thoracic aorta was identified in its long axis as a straight tubular structure with parallel walls. The transducer was then rotated approximately 90 degrees, to visualize the descending aorta in its short axis as a circular structure. This "paravertebral approach" has not previously been reported. In both patients, the retrocardiac descending thoracic aorta was clearly visualized in its long and short axes, and the oscillating intimal flap was visualized within the descending aorta in the paravertebral approach. Pulsed Doppler echocardiography (PDE) using the long-axis paravertebral approach identified the flow in the false and true lumens of the descending thoracic aorta. Flow patterns including the peak flow velocity and the velocity profile obviously varied between the true and false lumens. The peak flow velocities in the former were extremely high compared to those in the latter. The former exhibited laminar profiles, but the latter showed some spectral broadening. By the same approach, the entrance tear was explored and the jet flow through the tear was detected in Case 1 by PDE, which had high flow velocity with wide spectral broadening and aliasing in systole and also had relatively low flow velocity with some spectral broadening in diastole. To our knowledge, there has been no previous report of detecting flow at the entrance tear by PDE. These cross-sectional echocardiographic studies suggest that the paravertebral approach may prove helpful in initially evaluating patients with symptoms or signs suggestive of acute dissecting aneurysms. However, comprehensive studies are necessary to define the sensitivity and specificity of these echocardiographic techniques in recognizing all types of dissecting aneurysms. PMID- 2933477 TI - [Morphological study of the sacroiliac joint of aged Japanese and macroscopic and microscopic observations on its articular surface]. AB - Little information has so far been obtained in anatomical investigation of the sacroiliac joint. The purpose of this study was to investigate the sacroiliac joints morphologically and pathologically for the purpose of revealing the cause of low back pain. The materials consisted of 24 cadavers with both sides of the sacroiliac joint present. Firstly, investigation was performed radiographically to determine the shape and slope of the joint at the anatomical position. Secondly, measurement of the articular surfaces on photographs was performed to show the average of various measurements e.g. area, circumference, length, width etc., further more the differences between sacral and iliac articular surfaces and that of sex were demonstrated. Next, macroscopic and microscopic investigations of the joint cartilage were were performed. In general, degenerative changes were seen in all specimens and marked changes were found on the middle-anterior part of the joint. PMID- 2933478 TI - [Effects of schizophyllan (SPG), an antitumor polysaccharide, on serum proteins- in ENNG induced canine gastric cancer]. PMID- 2933479 TI - Isolation of apolipoprotein(a) from lipoprotein(a). AB - An easy method was developed for the rapid and selective isolation of apo(a) from human plasma Lp(a). This procedure was applied to a "low density" Lp(a) subspecies (usually found in the density interval 1.050 to 1.070 g/ml) from a single individual whose apo(a) was of a size smaller than apoB-100. After reduction with 0.01 M dithiothreitol, apo(a) was separated from the Lp(a) particle by rate zonal centrifugation on a 7.5-30% NaBr density gradient. Two completely water-soluble products were recovered: apo(a), which contained less than 1% each of phospholipid and cholesterol, remained at the bottom of the gradient, and a lipid-rich floating LDL-like particle which contained apoB but not apo(a) and which we referred to as Lp(a-). The separation of these two components was also achieved by subjecting reduced Lp(a) to electrophoresis on 2.5-16% polyacrylamide gradient gels. However, dissociation of reduced Lp(a) could not be achieved by gel filtration in either low or high salt solutions. These observations indicate that apo(a) is associated to Lp(a) by non-covalent interactions in addition to its disulfide linkage to apoB. The latter is sensitive to chemical reduction whereas the former are broken through the action of a gravitational or electrical field. PMID- 2933480 TI - Changes in total and free concentrations of steroid hormones in the plasma of women throughout pregnancy: effects of medroxyprogesterone acetate in the first trimester. AB - The total (protein-bound plus free) and free concentrations of progesterone, oestradiol-17 beta and cortisol were measured serially throughout pregnancy in the plasma of two groups of women whose pregnancies went to term. Group A (n = 53) experienced an uneventful low-risk pregnancy with a spontaneous abortion rate of 8.6%. Women in group B (n = 22) were treated orally with medroxyprogesterone acetate (MPA; 80-120 mg daily) until 18 weeks gestation for threatened abortion within the first 6 weeks of pregnancy. In both groups of women the proportion of each hormone circulating in the free or unbound form remained constant despite the overall increases with occurred in total circulating hormone concentrations as pregnancy progressed. The steroid hormonal profiles in the first half of pregnancy were similar in both groups of women. However, from weeks 20 to 40 total and free progesterone concentrations were significantly (P less than 0.05 in each case) higher in group B compared with group A. Conversely, total and free oestradiol-17 beta concentrations were lower (P less than 0.005 and P less than 0.01 respectively) in group B. At this stage it is not known if these differences were attributable to the administration of MPA to women in group B or to altered placental steroidogenesis as a result of earlier uterine bleeding. PMID- 2933481 TI - Physiology of IgD. VI. Transfer of the immunoaugmenting effect of IgD with T delta-containing helper cell populations. AB - We show that the IgD-induced augmentation of the immune response to trinitrophenylated keyhole limpet hemocyanin can be transferred to syngeneic mice with spleen cells from IgD-injected donors. The augmenting activity is present in the Lyt-1+2-, L3T4+ T cell population and is absent from B cells. The ability of transferred T cells to augment the immune response correlates with the presence of a high frequency of Lyt-1+2- T cells that form rosettes with IgD-coated sheep erythrocytes (T delta cells). Such rosette-forming cells can also be induced by incubation of spleen cells from normal donors in IgD-coated petri dishes. Injection of normal spleen cells exposed to IgD-coated petri dishes together with antigen also augments the immune response of recipients. The existence of a regulatory circuit based upon interactions between T delta cells, antigen, B cell surface IgD, and serum IgD, is proposed. PMID- 2933484 TI - An agarose gel electrophoretic method for typing phosphoglucomutase-1, esterase D, or glyoxalase I. AB - A conventional agarose gel electrophoretic method was described for typing phosphoglucomutase-1, esterase D, or glyoxalase I as single systems. Bloodstain extracts were absorbed into 1-mm-thick agarose gels via an application mask. The electrode wick distance was 12 cm and electrophoresis was carried out at 400 V at 6 degrees C. The electrophoretic run times were 30 min for glyoxalase and 1 h for esterase D or phosphoglucomutase. This method is reliable and produces highly resolved band patterns. Additionally, the shorter separation times as a result of the increased voltage gradient permitted typing of more samples in a given time period compared with presently used methods. This technique requires little technical expertise and can be incorporated into the laboratory at a minimal cost. PMID- 2933482 TI - Reevaluation of reserpine-induced suppression of contact sensitivity. Evidence that reserpine interferes with T lymphocyte function independently of an effect on mast cells. AB - It has been suggested that reserpine blocks expression of delayed hypersensitivity (DH) by depleting tissue mast cells of serotonin (5-HT), thereby preventing a T cell-dependent release of mast cell 5-HT necessary to localize and to amplify the DH response. However, reserpine blocks expression of DH in mast cell-deficient mice. We therefore decided to reevaluate the mechanism by which reserpine abrogates expression of cellular immunity, and investigated whether the drug might interfere with T cell activity in vitro or in vivo. At concentrations as low as 4 microM, reserpine profoundly suppressed baseline or antigen-augmented levels of [3H]thymidine incorporation by immune lymph node cells obtained from mice sensitized to the contactant oxazolone [I-LNC(Ox)]. This effect was observed both with I-LNC derived from normal mice and with I-LNC derived from congenitally mast cell-deficient W/Wv mice, cell preparations that lacked detectable mast cells, histamine, and 5-HT. Furthermore, treatment of I-LNC with reserpine (20 microM) for 1 h in vitro virtually abolished the ability of these cells to transfer CS to naive mice. This was not a cytolytic effect, as the viability of the I-LNC treated with reserpine was not affected, and washing of the reserpine treated I-LNC before transfer fully restored their ability to orchestrate a CS response. The action of the drug was not mediated by an effect on mast cells, since the experiment could be performed using mast cell-deficient W/Wv mice as both donors and recipients of I-LNC. In addition, the effect was specific for the treated cells: mice that received reserpine-treated I-LNC(Ox) intravenously together with untreated I-LNC(DNFB) did not develop CS to Ox but responded normally to DNFB; and local intradermal injection of reserpine-treated I-LNC(Ox) which failed to transfer reactivity to Ox, did not interfere with the development of CS to DNFB at the same site. Finally, cotransfer experiments indicated that the effect of reserpine on the transfer of CS was not due to activation of suppressor cells. Our findings strongly suggest that whatever effects reserpine might have on immunologically nonspecific host cells, the drug's effects on sensitized T cells are sufficient to explain its ability to block cell-mediated immune responses in vivo. PMID- 2933483 TI - Properties of purified T cell subsets. I. In vitro responses to class I vs. class II H-2 alloantigens. AB - In light of the widely accepted view that Ia-restricted L3T4+ T helper cells play a decisive role in controlling the differentiation of Lyt-2+ cells, experiments were designed to examine whether Lyt-2+ cells can respond to antigen in the absence of L3T4+ cells. The results showed that highly purified Lyt-2+ cells gave high primary mixed lymphocyte reactions (MLR) to various class I differences, including both mutant and allelic differences; responses to class II (Ia) differences were generally undetectable with Lyt-2+ cells. The intensity of MLR to class I differences was not affected by addition of anti-L3T4 monoclonal antibodies (mAb) to the cultures or by removing T cells from the stimulator populations. Negative selection experiments showed that Lyt-2+ cells could respond to class I differences across Ia barriers. MLR of purified Lyt-2+ cells peaked on days 3-4 and then fell sharply; background responses with syngeneic stimulators (auto-MLR) were virtually absent. Parallel experiments with purified L3T4+ cells showed that this subset responded in MLR only to class II (Ia) and not class I differences, reached peak responses only on day 6 rather than days 3 4, and often gave high auto-MLR. Within the first 3-4 d of culture, MLR were generally higher with Lyt-2+ cells than L3T4+ cells. Although no evidence could be found that Ia-restricted L3T4+ cells were required for the response of Lyt-2+ cells, presentation of antigen by Ia+ cells appeared to be essential. Thus, responses were ablated by pretreating stimulator cells with anti-Ia mAb plus C'. Significantly the failure of Lyt-2+ cells to respond to anti-Ia plus C'-treated stimulators could not be restored by adding syngeneic spleen cells; addition of IL-2 led to only a minor (15%) restoration of the response. It is suggested that Ia+ cells provide an obligatory second signal required by Lyt-2+ cells. PMID- 2933485 TI - Molecular cloning of a Bacillus subtilis gene involved in spore outgrowth. AB - A lambda Charon 4A derivative carrying the outB gene of Bacillus subtilis has been identified by transformation of a B. subtilis mutant temperature-sensitive in spore outgrowth. The cloned region is a single EcoRI fragment 14 kb in length. In addition to outB, the cloned DNA includes at least part of the amyE and aroI loci. PMID- 2933486 TI - Methanol dissimilation in Xanthobacter H4-14: activities, induction and comparison to Pseudomonas AM1 and Paracoccus denitrificans. AB - Methanol dissimilatory enzymes detected in the methanol autotroph Xanthobacter H4 14 were a typical phenazine methosulphate-linked methanol dehydrogenase, a NAD+ linked formate dehydrogenase, and a dye-linked formaldehyde dehydrogenase that could be assayed only by activity stains of polyacrylamide gels. This same methanol dehydrogenase activity was found in ethanol-grown cells and was apparently utilized for ethanol oxidation. Formaldehyde dehydrogenase activities were investigated in Paracoccus denitrificans, Xanthobacter H4-14, and Pseudomonas AM1. P. denitrificans contained a previously reported NAD+-linked, GSH-dependent activity, but both Xanthobacter H4-14 and Pseudomonas AM1 contained numerous activities detected by activity stains of polyacrylamide gels. Induction studies showed that in Xanthobacter H4-14, a 10 kDal polypeptide, probably a dehydrogenase-associated cytochrome c, was co-induced with methanol dehydrogenase, but the formaldehyde and formate dehydrogenases were not co regulated. Analogous induction experiments revealed similar patterns in P. denitrificans, but no evidence for co-regulation of dissimilatory activities in Pseudomonas AM1. PMID- 2933487 TI - The Disability Factor Scale--General: second-order factor structure. AB - This study examined the second-order factor structure of Siller's (1969) Disability Factor Scale--General. Factor analysis of the seven attitudinal factors toward disabled individuals, based on the responses of 200 college students, yielded two major second-order factors. These two second-order factors of Net Affect and Authoritarian Virtuousness are further discussed in light of their intrafactor and interfactor relationships. PMID- 2933488 TI - Central 5-HT and the respiratory response to acoustic stimulation in awake rats: effects of PCPA, 5-HTP and 8-OH-DPAT. AB - It was found that PCPA (4 X 50-100 mg/kg) decreased the respiratory response to tone pulses (acoustic reaction), and this effect was antagonized by the administration of 5-HTP (25 mg/kg), after inhibition of extracerebral aromatic amino acid decarboxylase by means of benserazide (25 mg/kg). A further increase in the dose of 5-HTP, 50-100 mg/kg, in animals not treated with PCPA did not significantly affect the acoustic reaction. The putative 5-HT agonist 8-OH-DPAT produced a decrease in the acoustic reaction (but also at higher doses some desynchronization of respiration with tone). The administration of d-amphetamine, 0.5-2.0 mg/kg, resulted in an increase in the acoustic reaction. Thus, in the present experiment, using a simple sensory-motor response, 8-OH-DPAT behaves as a 5-HT antagonist and the results provide further support for mixed 5-HT receptor agonist/antagonist properties of this compound. PMID- 2933489 TI - Dopamine D2 receptors in brain and anterior pituitary recognize agonist and antagonist actions of (-)-3-PPP. AB - (-)-3-PPP, is a unique dopamine analogue, reported to have selective agonist actions at dopamine autoreceptors and antagonist actions at postsynaptic receptors. The interactions of D2 dopamine receptors with (-)-3-PPP in vitro were examined, using [3H]spiperone to label D2 receptors in brain regions containing both pre- and postsynaptic D2 receptors (caudate nucleus, corpus striatum) and a region containing nonsynaptic D2 receptors (anterior pituitary). In the absence of sodium ions, (-)-3-PPP detected D2 receptors in high- and low-affinity states in all regions examined, as is typical of dopamine agonists. That these two subpopulations of (-)-3-PPP-detected sites were dopaminergic in nature was assured by precluding [3H]spiperone binding to serotonergic receptors. In the presence of sodium ions, there was a significant increase in the affinity of some D2 receptors detected by (-)-3-PPP, and (-)-3-PPP in the presence of sodium was unable to discriminate between the two D2 affinity states in pituitary and striatum. The addition of guanine nucleotide led to (-)-3-PPP recognition of a single D2 binding site; the enhanced affinity of D2 receptors for (-)-3-PPP in the presence of sodium was retained in the presence of guanine nucleotide. These in vitro characteristics of (-)-3-PPP recognition of dopamine D2 receptor binding sites, when compared with dopamine and spiperone are seen to have clear features of both typical agonist and antagonist interactions with D2 receptors in both brain and pituitary. PMID- 2933490 TI - [3H]1-[2-(4-aminophenyl)ethyl]-4-(3-trifluoromethylphenyl)piperazine: a selective radioligand for 5-HT1A receptors in rat brain. AB - 1-[2-(4-Aminophenyl)ethyl]-4-(3-trifluoromethylphenyl)piperazine (PAPP) inhibits [3H]5-hydroxytryptamine (5-HT, serotonin) binding to 5-HT1A and 5-HT1B sites in rat brain with apparent equilibrium dissociation constants (KD) of 2.9 and 328 nM, respectively. [3H]PAPP was synthesized, its binding to central serotonin receptors was examined, and its potential usefulness as a 5-HT1A receptor radioligand was evaluated. With either 10 microM 5-HT or 1 microM 8-hydroxy-2-(di n-propylamino)tetralin to define nonspecific binding, [3H]PAPP bound to a single class of sites in rat cortical membranes with a KD of 1.6 nM and a maximal binding density (Bmax) of 162 fmol/mg of protein. d-Lysergic acid diethylamide and 5-HT, two nonselective inhibitors of [3H]5-HT binding, displaced 1 nM [3H]PAPP with a potency that matched their affinity for 5-HT1 receptors. Spiperone and 8-hydroxy-2-(di-n-propylamino)tetralin, two compounds that discriminate [3H]5-HT binding to 5-HT1A and 5-HT1B sites, inhibited [3H]PAPP binding in accordance with their much higher affinities for the 5-HT1A receptor subtype. Furthermore, the ability of N-(m-trifluoromethylphenyl)piperazine and ketanserin to inhibit [3H]PAPP binding reflected their low affinities for the 5 HT1A receptor. Several nonserotonergic compounds were also found to be relatively poor displacers of [3H]PAPP binding. The regional distribution of serotonin sensitive [3H]PAPP sites correlated with the densities of 5-HT1A receptors in the cortex, hippocampus, corpus striatum, and cerebellum of the rat. These results indicate that [3H]PAPP binds selectively and with high affinity to 5-HT1A receptor sites in rat brain. PMID- 2933491 TI - Lymphocyte subpopulations in ataxia-telangiectasia. AB - Peripheral blood lymphocyte subsets were analyzed in nine patients with ataxia telangiectasia (AT) and their immediate family members. Absolute lymphocyte numbers were slightly low. T-helper/inducer cell, as well as B-cell, percentages were comparable to normal in patients with AT. The percentage of T suppressor/cytotoxic cells was decreased in five of nine patients. The percentage of large granular lymphocytes was elevated in three patients. No generalities consistent with a disease hypothesis could be made on the basis of lymphocyte subpopulation data. PMID- 2933494 TI - Herpetic whitlow: an infectious occupational hazard. AB - Herpetic whitlow is a herpes simplex virus infection of the finger. It may be caused by either herpes simplex type 1 or 2. It is characterized by pain, erythema, and nonpurulent vesicle or bullae formation. It may be due to a primary or recurrent infection. It is a common infection in health care professionals who have frequent contact with the secretions of patients' mouths and respiratory tracts. The diagnosis of herpetic whitlow may be confirmed by Tzanck test, acute and convalescent herpes simplex antibody titers, viral culture, and fluorescent antibody tests. The infection is self-limited, and surgical intervention generally should be avoided. Techniques for prevention and control of the infection include appropriate isolation of patients with herpes infections, avoidance of patient care by health care personnel with active infections, and the use of gloves when handling secretions. PMID- 2933492 TI - A controlled evaluation of recent approaches to biochemical modulation or enhancement of 5-fluorouracil therapy in colorectal carcinoma. AB - Three hundred thirty-five previously untreated patients with advanced colorectal carcinoma were randomly assigned to treatment with 5-fluorouracil (5-FU) alone, 5 FU plus N-(phosphonacetyl)-L-aspartic acid (PALA), 5-FU plus high-dose thymidine, 5-FU plus levamisole, or 5-FU plus methyl CCNU, vincristine, and streptozotocin (MOF-Strept). Dosages were designed to produce definite toxicity in the majority of patients, although the nature of dose-limiting reactions varied considerably among regimens. 5-FU alone and 5-FU plus levamisole produced mucocutaneous reactions, diarrhea, and leukopenia; 5-FU plus PALA produced primarily mucocutaneous reactions and diarrhea; 5-FU plus thymidine produced leukopenia with occasional neurotoxicity and hypotension; and MOF-Strept produced substantial nausea and vomiting with both thrombocytopenia and leukopenia. Objective response rates among patients with measurable disease varied from 12% (5-FU plus PALA) to 34% (MOF-Strept), but none of the regimens were significantly superior to 5-FU alone. Both interval to progression and survival were comparable among the five regimens with no reasonable chance that any combination regimen could produce as much as a 50% improvement when compared with 5-FU alone. Whereas we observed definite modulation of 5-FU dose--toxicity relationships, particularly with the thymidine and PALA combinations, this did not result in a detectable improvement in therapeutic effect. None of the combination regimens, administered in the dosages and schedules we used, can be recommended as standard therapy of advanced colorectal carcinoma. PMID- 2933493 TI - Effect of dietary orotic acid on the levels of liver and blood NAD in rats. AB - The effect of dietary orotic acid on the levels of liver and blood NAD in young rats was investigated. Weanling rats were fed on a nicotinic acid-free, 20% casein diet containing 0% (control diet) or 1% orotic acid (test diet) for 32 days. Retardation of growth, development of fatty liver and enlargement of liver were observed in the test group in comparison with the control group. In the test group, the amounts of quinolinic acid, niacin, NAD and N1-methylnicotinamide, and the activities of quinolinate phosphoribosyltransferase, nicotinamide mononucleotide adenylyltransferase, nicotinamide methyltransferase and NAD synthetase expressed in terms of g liver were significantly decreased compared to the control group. When these values were expressed in terms of whole liver, a significant difference was observed in the content of NAD and the activity of NAD synthetase between the control and the test groups. The activity of aminocarboxymuconate-semialdehyde decarboxylase expressed in terms of whole liver was about 2-fold higher in the test group than in the control group, but was not significantly different. The levels of NAD in blood as well as in liver were significantly lower in the test group than in the control group. Urinary excretions of quinolinic acid, niacin and N1-methylnicotinamide were also reduced in the test group. These results are discussed in the light of the reported effect of orotic acid in lowering the level of ATP in liver. PMID- 2933495 TI - Approach to asbestos worker compensation plan alleged to be flawed. PMID- 2933496 TI - Workers' compensation claims for stress-related disorders. PMID- 2933497 TI - Obesity, acanthosis nigricans, insulin resistance, and hyperandrogenemia: pediatric perspective and natural history. AB - We studied the syndrome of acanthosis nigricans, obesity, insulin resistance, and hyperandrogenemia in 22 patients. Although isolated case reports in adolescents have appeared, this syndrome has not received full recognition as a pediatric entity. Our patients (17 girls, five boys) had a mean weight 5.7 SD above the mean for age, although mean height was only 0.5 SD above the mean for age. All patients had acanthosis nigricans. Their insulin resistance was significantly greater than that in a control group with comparable obesity. Fasting insulin concentration was 5.25 microU/ml in lean controls, 19.6 microU/ml in obese controls, and 49.8 microU/ml in study patients (P less than 0.002). Mean glucose disappearance rate during an insulin tolerance test was 6.7%/min in lean controls, 5.19%/min in obese controls, and 2.35%/min in study patients (P less than 0.02). After menarche, mean plasma testosterone concentration was 106 ng/dl, compared with less than 50 ng/dl in all lean and obese control patients. Data derived from our series of patients lead us to conclude that (1) this is a genetic syndrome, although the exact mode of inheritance is unclear; (2) the natural history of the syndrome invariably begins with the onset of obesity, followed by acanthosis nigricans that worsens with progressive weight gain; (3) acanthosis nigricans is thus a marker for hyperinsulinemia, which occurs before hyperandrogenemia; (4) hyperandrogenemia occurs only after menarche. Identification of this syndrome should permit monitoring for the development of hyperandrogenemia during puberty and determination of other affected family members. PMID- 2933499 TI - Gingival crevicular fluid antibody to oral microorganisms. II. Distribution and specificity of local antibody responses. PMID- 2933498 TI - Mechanisms involved in the binding of IgG immune complexes to sections of inflamed gingiva. PMID- 2933500 TI - Gingival crevicular fluid antibody to oral microorganisms. III. Association of gingival homogenate and gingival crevicular fluid antibody levels. PMID- 2933501 TI - IgG, IgA and IgM serum antibodies against lipopolysaccharide from Bacteroides gingivalis in periodontal health and disease. PMID- 2933503 TI - Interaction of phenytoin and inflammation induces gingival overgrowth in rats. PMID- 2933502 TI - Microbial changes associated with advancing periodontitis in STR/N mice. PMID- 2933504 TI - Characterization of hydrogen sulphide reaction with rat-tail tendon type I collagen in vitro. PMID- 2933505 TI - Disturbances in bone remodeling during the progress of hamster periodontitis. A morphological and quantitative study. PMID- 2933506 TI - New attachment formation on citric acid treated roots. PMID- 2933507 TI - The susceptibility of experimental glomerulonephritis in six different strains of mice. AB - An experimental glomerulonephritis was produced in mice by an injection with a sub-nephrotoxic dose of nephrotoxic serum after immunization with rabbit IgG. In order to examine the susceptibility of disease, we tested the onset of nephritis in 6 different strains (ICR,C57BL/6,C3H,DBA/2, nu/nu and DDY) of mice. Strain C57BL/6 mice indicated the highest susceptibility to the disease with a high degree of reproducibility. The excretion of protein in urine, the elevation of serum cholesterol and blood urea nitrogen level and the decrease of serum albumin were observed in nephritic mice. Typical histopathological changes in the kidney were crescent formation in glomeruli, thickening of glomerular basement membrane and cast of urinary tubuli. Cyclophosphamide, at doses of 5 and 10 mg/kg, inhibited the development of nephritis in C57BL/6 mice. These results suggest that the experimental glomerulonephritis model in C57BL/6 mice is useful for immunopharmacological studies of nephritis. PMID- 2933508 TI - [Studies for developing hetero-bifunctional reagents and their applications in enzyme immunoassay]. PMID- 2933509 TI - [Effects of staphylococcal phage lysate (SPL) on immunoglobulin production in human peripheral lymphocyte cultures]. PMID- 2933510 TI - Inhalation of nail dust from onychomycotic toenails. Part I. Characterization of particles. PMID- 2933511 TI - Fifth metatarsal excision with peroneus brevis transfer. A case report. PMID- 2933512 TI - [Regeneration and myogenesis of striated muscle]. PMID- 2933513 TI - Microleakage at the gingival wall with four Class V anterior restorative materials. PMID- 2933514 TI - Dimensions of experience and symptomatology. AB - Six characteristics of life events and difficulties, namely loss (L), threat (T), anti-social act (A), hopeless situation (H), uncertain outcome (U) and choice of action (C), were used to score life situations experienced by 1060 adults over three months. Certain patterns of these, together with the respondents' sex, close and more superficial support discriminated significantly between subjects who had: depression the predominant symptom, anxiety predominant, tiredness predominant, backache predominant, none of these reaching pathological level. A hierarchy emerged from depression down through anxiety to tiredness and backache such that more severe life situations were associated with symptoms higher up the hierarchy. Situations with both choice of action (C) and loss (L) tended to be associated with depression. Anxiety related situations were mainly those containing threat (T) and at least two other characteristics. Tiredness went with situations characterised purely as CUH or CH or UH, and backache with minor situations containing only one characteristic. Lack of close confidant was most associated with depression; being a woman was associated with tiredness and anxiety equally and lack of superficial support with anxiety and depression equally. A parallel was drawn with Finlay-Jones and Brown. PMID- 2933515 TI - Pain and deception: use of verbal pain measurement as a diagnostic aid in differentiating between clinical and simulated low-back pain. AB - The pain reports of 553 patients with low back pain and 347 healthy subjects faking low back pain were compared to determine if pain language can be employed as diagnostic aids in differentiating between clinical groups and groups attempting to feign a clinical condition. The best set of discriminating words correctly identified 90% of the subjects using 18 to 54 words in pain description, and 83% using 4 to 17 words in their pain report. The same pain words were used to categorize 366 new pain cases and 202 new fake cases. Cross validation shrinkage was 8 and 7% respectively. Effectiveness in discriminating between pain and simulation was increased using selective cut-off scores. Patients in active treatment for back pain whose choice of pain words resemble those of the simulators reported 21% more clinical pain in a follow-up validation study suggesting that an accurate representation of malingering may have been achieved using a simulation research design. PMID- 2933516 TI - Psychological adjustment to and recovery from laparoscopic sterilization and infertility investigation. AB - One hundred and thirty-one patients undergoing elective laparoscopic surgery for sterilization or infertility investigations were examined in a prospective study. Firstly, the contributions of the reason for undergoing the operation to the patients' psychological adjustment and recovery, is examined. Measures were taken of personality, mood, physical symptoms, vital signs and the patients' speed of returning to normal activities. The reason for laparoscopy does not appear to influence the amount of fear immediately before and after the operation, post operative physical symptoms, nor the majority of mood states at follow up. There were significant differences between infertility and sterilization patients on state anxiety on the morning of surgery, vital signs, post-operative intramuscular analgesia, and the speed of returning to normal activities. In particular, sterilization patients did not report greater pain but received more analgesia, and returned to their normal activities more rapidly than infertility patients. Secondary infertility patients showed the slowest rate of return to normal activities, and reported more adverse mood states at 1 week follow up. The investigation of patients' attitudes to the operation revealed that patients undergoing sterilization and infertility investigation are concerned about the costs and benefits of the operation which include not only influencing fertility, but influencing menstruation and sexual activity. Patients misunderstood information about surgery, and the majority of patients welcomed additional psychological preparation. Suggestions concerning the management of patients undergoing laparoscopy for different fertility reasons are discussed. PMID- 2933517 TI - Novel vasopressin analogues that help define a minimum effective antagonist pharmacophore. PMID- 2933519 TI - Orally absorbable cephalosporin antibiotics. 1. Structure-activity relationships of benzothienyl- and naphthylglycine derivatives of 7 aminodeacetoxycephalosporanic acid. AB - A structure-activity relationship study of a number of orally absorbed cephalosporins together with their syntheses is described. These new cephalosporins are benzothienyl- and naphthylglycine derivatives of 7 aminodeacetoxycephalosporanic acid. Several different synthetic methods for the glycine side chains, their protection, and the final acylations are reported. Several of these analogues were more active than cephalexin both in vitro and in vivo against commonly encountered Gram-positive bacteria. (R)-7-(3 Benzothienylglycylamido)-3-methyl-3-cephem-4-carboxylic acid (1R) has emerged as a potent antibacterial agent and is currently undergoing preclinical evaluation. PMID- 2933520 TI - Orally absorbable cephalosporin antibiotics. 3. Preparation of biologically active R isomer of 7-(3-benzothienylglycylamido)deacetoxycephalosporanic acid. AB - The methyl and isopropyl esters of (RS)-3-benzothienylglycine were resolved with (+)- and (-)-tartaric acid in acetonitrile to give the corresponding R and S salts. The R-salt 4 was hydrolyzed to (R)-3-benzothienylglycine (5). The amino group in 5 was protected with the Boc function and the protected R amino acid 6 coupled with the p-NB ester of 7-ADCA to give the diprotected cephalosporin 7. After removal of the Boc and p-NB groups, the R isomer of 7-(3 benzothienylglycylamido)deacetoxycephalosporanic acid (1) was obtained. The p-NB ester of epimeric cephalosporin 7 was separated by preparative chromatography into R and S isomers. After removal of the protective groups, the S epimer was isolated. The comparison of antibacterial activity of the R and S epimers and the RS mixture of cephalosporin 1 is reported. PMID- 2933518 TI - Stereoselectivity of muscarinic receptors in vivo and in vitro for oxotremorine analogues. N-[4-(tertiary amino)-2-butynyl]-5-methyl-2-pyrrolidones. AB - The enantiomers of three 5-methyl-2-pyrrolidone analogues of the muscarinic agent oxotremorine (1) were synthesized. The pyrrolidine derivative (R)-13 was an antagonist to carbachol in the guinea pig ileum and also showed central and peripheral antimuscarinic activity in vivo. It was more potent and more selective than atropine in antagonizing the central effects of 1. The dimethylamino analogue (R)-14 and the trimethylammonium salt (R)-15 were potent agonists in the guinea pig ileum. (R)-14 showed both central muscarinic (hypothermia) and central antimuscarinic activity (antagonism of oxotremorine-induced tremor) in vivo. The R enantiomers of 13-15 were considerably more potent than the S enantiomers in vivo and in vitro irrespective of whether agonist or antagonist activity was measured. From a comparison of the contribution of the methyl group at the chiral center to the overall affinities, it is suggested that agonists and antagonists in this series bind in an essentially identical manner to the muscarinic receptor. PMID- 2933521 TI - Unusual properties of Staphylococcus aureus strains of the new epidemic phage type 95. AB - Three hundred and seventy-one penicillin-resistant Staphylococcus aureus strains of phage type 95 isolated in the years 1977-1983 were investigated. They had characteristic resistance patterns to cadmium (Cd), arsenate (As) and mercury (Hg). Most were susceptible to all three heavy metals; 25 strains were resistant to As only and one to Cd and As. The susceptible strains had a uniform medium level of penicillinase production, whereas the As-resistant strains produced large amounts of penicillinase. In most of the strains, penicillin resistance was located on a very unstable penicillinase plasmid. The combination of rare properties found in Danish type-95 strains seems to point to the spread of one or two clones. Co-reactions with other phage groups or complexes and results of lysogenisation experiments suggest that the Danish type-95 strains are derived from strains of the 52, 52A, 80, 81 complex. PMID- 2933522 TI - Age changes in the flexibility of Down's syndrome children. AB - The association between Down's syndrome (DS) and joint hyperflexibility is well documented. However, objective information concerning developmental expectations for flexibility in DS children is lacking. This investigation used goniometric techniques to examine the changes in flexibility with growth and maturation in 30 DS children aged 5, 10 and 15 years and compared them with 30 normal controls. Flexibility declined consistently with age in the DS children and in the controls, and although the DS children were more flexible than their control counterparts at each age, the magnitude of change over the whole age range was parallel in both groups of children suggesting some similarity in mechanisms controlling the maturation of joint tissues. The greatest reduction in flexibility occurred in the hip and ankle joints, and in the elbow and knee hyperextension. A trend was evident for the largest reduction in measurements to occur between 5 and 10 years in the DS children compared with a consistent or later reduction in the controls. It is postulated that this may be attributable to the improvement in generalized muscular hypotonia expected during this age period, or to differences in the rate of maturation of joint structures in the early years, caused by the effects of the syndrome on the intrinsic mechanisms regulating the growth of joints. PMID- 2933523 TI - A double blind study of vitamin B6 in Down's syndrome infants. Part 1--Clinical and biochemical results. AB - Nineteen patients with Down's syndrome participated in a double blind study of the clinical effects of pharmacological doses of vitamin B6 administration, starting under 8 weeks of age and continuing until 3 years of age. Ten patients received the vitamin and nine the placebo. In Part 1 of this study, no statistically significant differences were found between the two groups in mental age, height, weight, cranial circumference or tongue protrusion. A study of side effects conducted on a larger open population found vitamin B6 to be relatively safe when administered over long periods of time with photosensitive blisters as the major complication. PMID- 2933524 TI - A double blind study of vitamin B6 in Down's syndrome infants. Part 2--Cortical auditory evoked potentials. AB - Cortical auditory evoked potentials (CAEPs) were recorded at 1 and at 3 years of age in 19 children with Down's syndrome participating in a double blind trial of vitamin B6 and placebo begun in early infancy and continued for 3 years. CAEPs have previously been shown to have abnormally high amplitude in Down's syndrome patients. The CAEPs of the patients in the B6-treated and placebo groups were compared. Only minor effects were found in the CAEPs recorded at 1 year of age. At 3 years of age, however, comparison of the B6-treated group and the placebo group revealed significant differences in both amplitudes and latencies of CAEP components. Peak to peak amplitudes of prominent components were significantly lower in B6-treated patients than in their placebo controls. Amplitude correlated in some cases with whole blood serotonin levels. Latencies for several prominent evoked peaks were significantly longer in B6-treated patients. PMID- 2933525 TI - Abnormally high sweat osmolality in children with Down's syndrome. AB - There are few data on sweat analysis in Down's syndrome. We studied 25 children with Down's syndrome and obtained sweat samples by pilocarpine iontophoresis. Sweat osmolality was elevated in Down's syndrome compared to normal. The results of sweat testing must be regarded with caution when cystic fibrosis is suspected in children with Down's syndrome. PMID- 2933526 TI - Turn-taking and overlap in the speech of young Down's syndrome children. AB - This study has examined incidents involving vocal overlap in recordings made in the homes of four 3-year-old Down's children. Previous research has suggested a higher incidence of vocal clashes and interruptions in the interaction of Down's children than in that of non-handicapped children. In our data, the overall incidence of overlaps initiated by the child was higher for the two less advanced children. However, such overlaps do not necessarily indicate poor turn-taking coordination; slight overlaps, and overlaps which occur close to where a speaker had reached a potential completion point in their turn, need to be distinguished from those which begin in the middle of turn-constructional units. The children's behaviour when overlap occurred was also examined. A number of techniques which show a child's awareness of the fact that overlap has occurred were identified. By using overlap-sensitive techniques, a child is treating overlap as a problem to be remedied. While the most advanced child used six such techniques, there was not clear evidence of the least advanced child using any of them. PMID- 2933527 TI - Regional myocyte size in compensated right ventricular hypertrophy in the ferret. AB - The effect of pressure-induced right ventricular hypertrophy on regional myocyte size and shape and regional myocardial wet weight was studied by comparing 20 ferrets which underwent pulmonary artery banding at a weanling age to 19 non operated siblings. Using isolated myocyte preparations from six myocardial regions in 10 banded and seven non-banded ferrets, a 60% increase in cell volume in the right ventricular outflow tract and the right ventricular free wall was shown to be due primarily to an increased cross-sectional area of individual myocytes. The right side of the interventricular septum exhibited an intermediate increase in cell volume, while the left side of the interventricular septum did not respond to the pulmonary artery banding procedure. These findings confirm that localized hemodynamic changes produce hypertrophy of individual myocytes in selected regions of the heart and that a pressure-induced model of hypertrophy involves an increased cross-sectional area of myocytes, with minimal change in cell length. PMID- 2933528 TI - Biochemical characterization of ventricular myosin from spontaneously hypertensive turkeys. AB - Several stimuli are able to alter the synthesis of cardiac myosin isoenzymes. Particularly in the rat a shift toward a low-ATPase isomyosin is generally observed during development and in cardiac hypertrophy due to pressure overload. On the contrary in spontaneously hypertensive turkeys both ageing and the increasing degree of cardiac hypertrophy are accompanied by a different behaviour of ventricular myosin. In fact in a previous study we have shown that the Ca2+ activated ATPase activity of ventricular myosin increases about three folds from young normotensive to old hypertensive animals. Accordingly the peptide pattern obtained after chymotryptic digestion of myosin showed that some peptides, which are not evident or barely discernible in young animals, are present in the adult ones. In this study we compare the ventricular myosin from young normotensive and adult hypertensive turkeys with atrial myosin. The results obtained suggest that in the ventricles of hypertensive turkeys the synthesis of an isomyosin with biochemical properties close to those of atrial myosin occurs. PMID- 2933529 TI - Characterization of the rat heart 6-phosphofructo-1-kinase isozymes. AB - By elution with a discontinuous gradient from QAE-Sephadex, the rat muscle 6 phosphofructo-1-kinase (PFK) isozyme (M4) and the major rat liver PFK isozyme (L4) could be completely separated. Subjecting heart supernatant fluid to this treatment indicated that all of the heart PFK activity was found in the first wash, where M4 eluted, indicating little, if any, L4 was present. However, about 50% of the heart PFK activity was immunoprecipitated by L4 anti-IgG demonstrating the presence of the L-type subunit. A purification procedure was developed which yielded an enzyme preparation of high specific activity and resulted in a recovery of 50% to 60% of the original PFK activity. Three proteins were detected in this PFK preparation that exhibited apparent mol wt of 87 500, 85 000 and 80 000. The 85 000 and 80 000 Dalton components corresponded to the subunits of M4 and L4, respectively. The third protein was thought to be a distinct subunit (C type) since it exhibited the highest molecular weight and was present in an exhaustively washed immunoprecipitate of purified heart PFK. From seven different heart PFK preparations, the relative distributions of the L-, M-, and C-type subunits were 0.80 +/- 0.1, 4.5 +/- 0.7, and 0.7 +/- 0.1, respectively. A comparison of the kinetic properties of L4, M4, and purified heart PFK isozymes clearly demonstrated that all three preparations exhibited different regulatory properties. In ventricular and atrial preparations the total PFK activity and the relative amounts of each subunit were drastically different suggesting regional differences between the distributions of PFK isozymes and consequently in regulation of PFK activities and glycolysis. PMID- 2933530 TI - Vaccination against hepatitis B in Nigerian children: trials of reduced dose and intradermal vaccine. PMID- 2933531 TI - Genetic and DNA mapping of the late regulation and lysis genes of Salmonella bacteriophage P22 and coliphage lambda. AB - Genetic and DNA heteroduplex analyses of lambda imm22 hybrid phages were used to compare the Salmonella bacteriophage P22 and coliphage lambda genes which control late gene regulation and lysis. Homologous DNA sequences were correlated with P22 gene 23 and lambda gene Q (late gene regulation) and with P22 gene 13 and lambda gene S (lysis control). Nonhomologous DNA sequences were correlated with P22 gene 19 and lambda gene R (lysozyme and endolysin) and with the region encoding the P22 alpha and lambda 6S transcripts. PMID- 2933532 TI - Obesity as a predictor of poor antibody response to hepatitis B plasma vaccine. AB - Factors associated with lack of antibody response to the hepatitis B virus plasma vaccine were retrospectively evaluated by means of a logistic regression in 194 previously seronegative staff members of a community hospital. All subjects had received three doses of vaccine by intramuscular buttock injection using a 1-in, 23-gauge needle. Overall, only 55.7% of subjects developed detectable antibody to hepatitis B surface antigen in serum after immunization. The weight-height index served as a surrogate measure of obesity. Predictors of poor immunogenic response to hepatitis B vaccine included higher weight-height index, older age, and vaccine batch. Sex, race, timing of vaccine doses, and timing of postimmunization determination of antibody to hepatitis B surface antigen were not predictors of vaccine efficacy. PMID- 2933533 TI - Normal immune response to hepatitis B vaccine in patients with Down's syndrome. A basis for immunization guidelines. AB - Institutionalized patients with Down's syndrome (DS) are uniquely predisposed to develop chronic hepatitis B infection following exposure. Therefore vaccination is particularly warranted, but there have been concerns that these individuals may react suboptimally. We examined the immune responses of 62 institutionalized patients with DS to 20 and 40 micrograms of hepatitis B vaccine inactivated (Heptavax-B) over one year. The subjects were matched by weight, age, and sex. Seroconversion rates and levels of antibodies to hepatitis B surface antigen (anti-HBs) were comparable to those found in a normal population and were higher than those found in immunocompromised patients undergoing hemodialysis. The anti HBs levels were consistently higher in the 40-micrograms vaccine group. In patients with DS who were over 30 years old, age was a significant factor in predicting anti-HBs responses. Conversely, in younger subjects, weight was negatively correlated with anti-HBs levels. These data clearly indicate that patients with DS respond normally to hepatitis B surface antigen vaccination and need not be considered a special group when guidelines for vaccination are recommended. PMID- 2933534 TI - Hepatitis B vaccine use in chronic hemodialysis centers in the United States. AB - The Centers for Disease Control surveyed 1,255 chronic hemodialysis centers in the United States in 1983 to assess the use of hepatitis B vaccine as well as the risk of acquiring hepatitis B among both patients and staff. The response rate to a mailed questionnaire was 90%. Seventy-one percent of the centers reported that they gave vaccine, but only an estimated 6% of susceptible patients and 32% of susceptible staff received all three doses of vaccine. Centers more likely to give vaccine included those that provided dialysis to large patient populations and those that provided dialysis for hepatitis B surface antigen-positive patients. As a result of vaccine administration, the overall prevalence of antibody to hepatitis B surface antigen increased significantly, to 18% for patients and 39% for staff. Extensive use of the vaccine in the future, combined with infection control practices, could virtually eliminate the risk of acquiring hepatitis B virus infection in hemodialysis centers. PMID- 2933535 TI - Clinical evaluation of low-dose intradermally administered hepatitis B virus vaccine. A cost reduction strategy. AB - High cost and limited availability of the current hepatitis B virus vaccine lead to underutilization. To address this problem, we performed a vaccine trial comparing the currently recommended regimen of 20 micrograms of hepatitis B surface antigen (HBsAg) intramuscularly on days 0, 30, and 180, with a more economical regimen of 2 micrograms of HBsAg intradermally on days 0, 30, and 180. This trial was performed in 50 seronegative health care workers to assess the immunogenicity and local reactogenicity of both vaccine regimens. We found no significant difference in seroconversion between the intradermal group (96%) and the intramuscular group (100%). Mean ratios of test sample value to mean negative control value for antibody to HBsAg at 360 days were not significantly different (intradermal group, 84 +/- 26; intramuscular group, 120 +/- 22). Reactions in both groups were minor. Although the optimal dose of HBsAg was not investigated, our data demonstrate that 0.1 mL of inactivated hepatitis B virus vaccine (Heptavax-B) intradermally is immunogenic in healthy adults. Vaccination by this regimen can broaden hepatitis B virus disease prevention. PMID- 2933536 TI - Clinical viral hepatitis B among Minnesota hospital personnel. Results of a ten year statewide survey. AB - We report a ten-year survey of clinical hepatitis B virus (HBV) infections in Minnesota hospital personnel. Between 1974 and 1983, a total of 561 personnel cases of viral hepatitis were identified. Four hundred twelve cases were diagnosed as type B, with 399 cases (97%) identified as work related. Of the 177 hospitals in the state, only 42 (24%) reported cases during the ten-year period. The highest annual incidence of type B cases was in 1975 (127/100,000 personnel) and decreased to the lowest incidence in 1983 (8/100,000 personnel). The incidence for personnel at hospitals with long-term hemodialysis decreased from 418/100,000 personnel in 1975 to 16/100,000 personnel in 1983, while the incidence for employees in hospitals without hemodialysis decreased from 16 to 5/100,000 personnel for the same time. The decrease in the incidence of hepatitis B in personnel occurred before the use of HBV vaccine. Our findings indicate that HBV seroprevalence studies significantly overestimate the current incidence of HBV infections among personnel in most hospital settings. PMID- 2933537 TI - Lowered cost potential for hepatitis B vaccine. PMID- 2933538 TI - Baboon-to-human cardiac xenotransplantation in a neonate. AB - This report details the first case of cardiac xenotransplantation in a neonate. The recipient, a victim of hypoplastic left heart syndrome (HLHS), survived 20 days. Autopsy findings are documented. The cardiac graft showed only traces of cell-mediated rejection. Graft failure appears to have resulted from a progressive, potentially avoidable humoral response, unmodified by immunosuppression. Cardiac allotransplantation and selective baboon-to-human xenotransplantation deserve further exploration as investigational therapy for neonatal HLHS. PMID- 2933539 TI - Fluorouracil-associated dermatitis of the hands and feet. PMID- 2933540 TI - Effects of alpha-human atrial natriuretic polypeptide (alpha-hANP) on the main regulatory mechanisms for blood pressure and body fluid volume in rats. PMID- 2933541 TI - Cardiac content and plasma concentration of atrial natriuretic polypeptide (ANP) in spontaneously hypertensive rats (SHR). AB - The cardiac content and plasma concentration of atrial natriuretic polypeptide (ANP) in hypertensive rats were measured by using radioimmunoassay for ANP. The animals used in this study were young (5-week-old) and adult (12- to 14-week-old) spontaneously hypertensive rats (SHR), stroke-prone SHR (SHR-SP) and normotensive control Wistar-Kyoto rats (WKY). Most immunoreactive ANP in the cardiac extract of the hypertensive rats (both SHR and SHR-SP) was found to be predominantly gamma-form as well as that of WKY. Cardiac ANP content in adult SHR and SHR-SP was significantly lower than in adult WKY (p less than 0.01), although there were no differences among three groups in young rats. Similar tendencies were also observed for plasma ANP concentration. The level of plasma in adult hypertensive rats was significantly lower or tended to be lower than in adult normotensive rats. Furthermore, a high negative correlation was present between blood pressure and cardiac ANP content (r = 0.748, p less than 0.01) and between blood pressure and plasma ANP concentration (r = 0.608, p less than 0.01) in all adult rats but there were no such relationships in young rats. The present study suggests that atrial natriuretic polypeptide may contribute to the pathogenesis or maintenance of high blood pressure in the genetic hypertensive rats. PMID- 2933542 TI - [Platelet aggregation and release reaction]. PMID- 2933543 TI - [Growth and exercise therapy for infants with Down's syndrome]. PMID- 2933544 TI - [Study of the in vitro effect of MPA on an established cell line from a human renal cell carcinoma]. PMID- 2933545 TI - [Analysis of reactions to urographic contrast media and an evaluation of pretesting]. PMID- 2933546 TI - Comparison of fluorescence and photodynamic activities of whole hematoporphyrin derivative and its enriched active components. AB - The in vivo biologic activities of the hematoporphyrin derivative (Photofrin) and the enriched, so-called "active fraction" (Photofrin II) were determined by measuring the necrosis produced in implanted tumors in DBA/2Ha mice exposed to various total doses of light (20-100 J/cm2) after ip administration of 10 mg/kg standard doses of either Photofrin or Photofrin II. Total relative percentage increase in fluorescence in tumor tissue, as compared to fluorescence in control tissue, also was measured for both Photofrin and Photofrin II. In response to total light doses (630 nm) of 40-100 J/cm2, mice that received Photofrin had comparable amounts of tumor necrosis to those mice that received Photofrin II. At doses of 40-60 J/cm2, 80% tumor destruction resulted, and at 80-100 J/cm2, tumor destruction was 100%. However, at a total light dose of 20 J/cm2, the tumors that received Photofrin II exhibited 60-80% tumor necrosis, whereas those animals that received Photofrin had only small areas of patchy necrosis associated with signs of vascular thrombosis and hemorrhage into the surrounding perivascular stroma. A 25.2% total increase in maximal tissue fluorescence over that in controls was observed for animals that received Photofrin II, as compared to 13.9% for those animals that received Photofrin. It is concluded that the greater demonstrable efficacy of treatment with Photofrin II, as compared to treatment with Photofrin, is due to enrichment of those nonpolar hydrophobic components of the hematoporphyrin derivative mixture that are thought to be primarily responsible for the in vivo biologic activities. PMID- 2933547 TI - [Chronic back pain/cot death]. PMID- 2933548 TI - [Aortocoronary shunt in a patient with unstable angina pectoris and subclavian artery stenosis, corrected by roentgen endovascular dilatation]. PMID- 2933549 TI - Mechanisms of glomerular injury in immune-complex disease. PMID- 2933550 TI - [Therapeutic laparoscopy in emergency pediatric surgery]. PMID- 2933551 TI - [Use of a double-lobed skin-fat flap of the abdominal wall in postburn deformities of the perineum]. PMID- 2933552 TI - [Doppler ultrasonography of orbital vessels in circulatory disorders of the eye]. AB - During the past 5 years 412 patients (189 male, 223 female) presenting with vascular disorders were examined with Doppler ultrasonography (DUSG) of the orbital vessels. DUSG was used as a screening method for detecting additional lesions of the carotid system. The 412 patients were divided into 5 groups according to their clinical symptoms: Group I: amaurosis fugax; group II: occlusions of the central retinal artery; group III: venous circulatory disorders of the retina; group IV: AION and optic disk vasculitis; group V: symptoms of chronic ocular ischemia. DUSG disclosed a high percentage of additional carotid lesions in groups I and II. In retinal venous disorders, in idiopathic non arteritic AION and in optic disk vasculitis DUSG findings usually were negative. In contrast to this, DUSG furnished valuable diagnostic information in arteritic AION, where nearly 50% of DUSG findings were positive. Carotid angiography, echo flow examination of the carotid system and temporal biopsy were used as reference methods. PMID- 2933553 TI - [Ulrich oculo-oscillodynamography: initial results in carotid stenoses]. AB - Oculo-oscillodynamography (OODG) after Ulrich was performed in 11 patients suffering from a monolateral, hemodynamically relevant carotid stenosis identified by Doppler sonography. All of the pressure parameters which can be measured by OODG--systolic retinal, systolic ciliary, and diastolic ocular perfusion pressure--were low on the side concerned. In contrast to the already established methods of measuring ocular perfusion--ophthalmodynamometry and ophthalmodynamography after Hager--the advantages of OODG are that it not only enables the systolic retinal pressure to be differentiated from the systolic ciliary or diastolic ocular perfusion pressure, but also permits the results of the investigation to be illustrated graphically, so that objective evaluation is possible. PMID- 2933554 TI - [Ophthalmodynamography and Doppler ultrasonography of orbital vessels in temporal arteritis]. AB - Twenty-three patients presenting with clinical and angiological signs of temporal arteritis were examined by ODG and DUSG. While the results of ODG were positive in all 23 patients, DUSG failed to furnish diagnostic evidence of temporal arteritis. Findings with DUSG were positive in only 9 out of 23 patients. DUSG is less suitable than ODG as a means of diagnosing temporal arteritis. PMID- 2933555 TI - Measurement of skin blood flow in patients with diabetes mellitus by periflux laser Doppler flowmeter. PMID- 2933556 TI - [Sanatorium treatment of duodenal ulcer patients over 50]. PMID- 2933557 TI - [Changes in the physico-chemical properties of contractile and regulatory proteins in muscles of different types during overload and readaptation]. AB - After 15-day exposure to +5 Gx the rate of superprecipitation, Mg2+-ATPase activity and actomyosin ATPase of slow muscles (m. soleus and medial head of m. triceps brachii) of white rats increased greatly. In actomyosin of fast muscles (m. brachialis and m. extensor digitorum longus) the exposure induced weaker and opposite changes in the superprecipitation rate and Mg2+-ATPase activity. The changes in actomyosin of the fast muscles were associated with shifts only in regulatory components while those of the slow muscles were produced by shifts in contractile proteins as well. This provided for a better recovery of the initial value of the superprecipitation rate and Mg2+-ATPase activity of actomyosin of the fast muscles a month after the exposure. PMID- 2933558 TI - [SAHB (Swiss Study Group for Resources for Handicapped) consultation. A sought after service for the physically disabled]. PMID- 2933559 TI - Cortisol, cortisone and dehydroepiandrosterone sulfate levels in umbilical cord and maternal plasma between 21 and 30 weeks of pregnancy. AB - Cortisol (F), Cortisone (E) and dehydroepiandrosterone sulfate (DHAS) were determined in maternal peripheral plasma and umbilical cord plasma between 21 and 30 weeks of amenorrhea. In fetal plasma, DHAS levels were the highest and those of F the lowest. E always exceeded F. The pattern of all these steroids was characterized by a plateau throughout the period considered. In maternal plasma, F levels were more elevated than those of E but lower than DHAS concentrations. All the steroids plateaued as in the fetus. The study of the correlation between the steroids in either the same milieu or in maternal and umbilical cord plasma demonstrated that fetal E was correlated with maternal F and with fetal F while fetal DHAS was inversely correlated with maternal E. PMID- 2933560 TI - Modulation of action of kainic acid on the behavior of rats by p chlorophenylalanine and by gaba-mimetic drugs. Biochemical correlation between behavior and treatments. AB - Systemic injection of kainic acid (KA, 11 mg/kg i.p.) to male albino Sprague Dawley rats produced a sequence of behavioral events: stereotypies, convulsions, aphagia and aggressiveness in the form of sparring at artificial night fall, as well as a decline in brain-Gaba and brain-dopamine (DA)-levels followed by an increase in DA-levels on days 6 and 10 after treatment. No notable variations in serotonin (5-HT) was observed. Pretreatments of rats with GABA-mimetic drugs (gamma-vinyl GABA, 900 mg/kg i.p.; THIP, 1 microgram/1 microliter/rat, i.c.v.) prevented the occurrence of convulsion, aphagia and aggressiveness. Systemic injection of p-chlorophenylalanine (PCPA) (300 mg/kg i.p.) induced aggressiveness in the form of sparring at night fall. Treatment with PCPA followed by injection of KA shifted mild aggressive behavior to a violent one in the form of biting and killing familiar rats. The findings suggest that KA-neurotoxicity is due in part to its effects on GABA- and DA-neurotransmissions. It is shown also that convulsions are induced by a decline in GABA-level while sparring is provoked by an enhancement in DA-level. Violent aggressiveness is induced by the additive disruptive effects on GABA- and 5-HT-neurotransmissions in PCPA + KA treated animals. PMID- 2933561 TI - A model of lambda DNA arrangement in the viral particle. AB - The icosahedral shape of the lambda head suggests a 12-subunit structure of the collapsed DNA inside. The internal space of an icosahedron can optimally be filled by 12 geometrical figures each of which is a combination of a cone and more than half of a sphere. Such a pear-like geometrical figure is, in fact, formed spontaneously by DNA collapsed under certain conditions in vitro (Eickbush & Moudrianakis, 1978). It is proposed that a pear-like structure formed by about 4000 bp is the fundamental structural subunit of packaged lambda DNA. A possible arrangement of the 12 subunits inside the phage head relative to the tail is discussed. We hypothesize that lambda DNA is packaged into proheads in its condensed form. A driving force promoting the DNA translocation could be an ATP dependent activity of a DNA topoisomerase (gpA/gpNu1), which would induce further reduction in the linking number of the already strongly negatively supercoiled DNA by rotation of one DNA strand around the other. The additional strain accumulated at the end of DNA molecule bound by the topoisomerase beyond a critical value would lead to regional collapse of the viral genome into a pear like structure. PMID- 2933562 TI - Externally stented polytetrafluoroethylene valved conduits for right heart reconstruction. An experimental comparison with Dacron valved conduits. AB - Valve-containing conduits have made possible the repair of many congenital anomalies that involve right ventricular-pulmonary arterial discontinuity. The distressing problem of neointimal peel formation with eventual conduit obstruction in patients with Dacron valved conduits has led to the need for premature replacement in many patients. Externally stented polytetrafluorethylene has demonstrated superior patency in the venous system experimentally and clinically and was believed to have potential advantages over Dacron for conduit construction. This study compares the transconduit resistance and the thickness of the neointimal peel in right ventricular-pulmonary arterial conduits constructed of externally stented polytetrafluoroethylene with those of woven Dacron. The 19 mm externally stented polytetrafluoroethylene conduits (Impra, Inc.) containing a Hancock porcine valve (Extracorporeal Inc.) were implanted in six adult mongrel dogs followed by proximal occlusion of the pulmonary artery. In six additional animals, a Dacron valved conduit of similar size and length was inserted. Cardiac output, transconduit gradient, and resistance were measured at operation and at 3 months. All conduits were subsequently explanted, opened longitudinally, and the thickness of the neointimal peel (excluding suture lines) measured. No hemodynamic differences were noted during the 3 month follow-up. However, the thickness of the neointimal peel was fourfold greater in Dacron conduits (609 +/- 144 mu) than in the conduits constructed of externally stented polytetrafluoroethylene (156 +/- 50 mu) (p less than 0.01). The thick peel in Dacron conduits extended into the outflow portion of the porcine valve cusps and prevented their full excision. The neointima in externally stented polytetrafluoroethylene conduits was thin and uniform and did not extend onto the leaflets or limit their mobility. This study demonstrated that the early hemodynamic performance of externally stented polytetrafluoroethylene conduits was comparable to that of Dacron conduits; Dacron conduits were subject to an accelerated rate of peel formation that affected leaflet mobility and may be a factor in early valve degeneration; a thin neointima formed in externally stented polytetrafluoroethylene conduits and valve leaflet motion was preserved. This study showed that externally stented polytetrafluoroethylene conduits offer advantages over Dacron valved conduits and warrant clinical application. PMID- 2933563 TI - A comparative study of immunological and cytochemical profiles between adult and childhood acute lymphoblastic leukemias (ALLs): heterogeneity in adult common ALL. AB - To investigate the biological differences between adult and childhood acute lymphoblastic leukemia (ALL), leukemic blasts from 33 patients with ALL (22 adults and 11 children) and from 11 patients in the lymphoid crisis of chronic myeloid leukemia (CML) were studied using cytochemical and immunological markers and also by the outcome of their treatment. The cytochemical studies showed that blasts from seven of the adult ALL patients were dense-granular-positive (DG positive) for beta-glucuronidase, whereas the blasts from the children were negative except for one (with T-ALL). In the adults with common ALL (cALL), survival of patients DG-positive for this enzyme were significantly shorter than that of eight patients with a scattered granular pattern (p less than 0.05). The mean ratio between the percentage of blasts positive for cALL antigen (cALLA) to that of blasts positive for terminal deoxynucleotidyl transferase (TdT) in the adult group with cALL (0.6 +/- 0.3) was significantly lower (p less than 0.01) than in the group of children with cALL (1.1 +/- 0.2) or in the lymphoid-crisis group (1.5 +/- 1.0). These findings indicate that adult cALL consists of two distinct subpopulations, one with less differentiated phenotype (cALL-/TdT+) and the other with more (cALL+/TdT+). In contrast, the blast cells in childhood cALL and some patients in lymphoid crisis had a relatively homogeneous population with the latter phenotypes. The results suggest that the clonotypic cells in adult ALL, particularly in cALL, appear to be more immature than those in childhood ALL. The beta-glucuronidase patterns indicate a further heterogeneity in adult ALL. PMID- 2933564 TI - Bone marrow macrophages and megakaryocytes express common acute lymphoblastic leukaemia antigen. AB - Common acute lymphoblastic leukaemia antigen (CALLA) was demonstrated on a proportion of bone marrow macrophages and megakaryocytes. CALLA was detected by two monoclonal antibodies (J5 & BA3) in a three-layer immunoalkaline phosphatase system applied to routine air-dried bone marrow smears. The J5 staining was confirmed by an indirect immunofluorescent method and the CALLA was shown to be at the surface of the macrophages and megakaryocytes by an indirect immunogold technique. The findings are discussed in relation to the known tissue distribution of CALLA and to the clinical use of anti-CALLA antibodies for bone marrow purging. PMID- 2933565 TI - Bronchodilator drugs and their combinations antagonize the dose-related leukotriene D4-induced airway obstruction in guinea pigs. AB - The effects of theophylline (THEO), terbutaline (TER), and ipratropium bromide (IPRA), given i.v. alone or in combination, were studied on leukotriene D4 (LTD4) induced airway obstruction in anaesthetized guinea pigs. LTD4 (0.1-1.6 microgram/kg i.v.) obstructed small airways more than large ones as assessed in terms of relative changes of lung resistance (RL) and dynamic lung compliance (CDyn). A slight tachyphylaxis to LTD4 was observed after repeated administration, especially in the responses of large bronchi. The airway effects of LTD4 were almost totally abolished by prior administration of indomethacin (5 mg/kg i.v.) suggesting a central role of secondarily released cyclo-oxygenase products in this model. THEO (1 to 20 mg/kg) and TER (10 to 400 micrograms/kg) antagonized dose-dependently the LTD4 (0.4 microgram/kg i.v.) induced rise in RL and decrease in CDyn, whereas IPRA (10 to 400 micrograms/kg) failed to show comparably activity. THEO 5 and 20 mg/kg proved highly efficient also on the dose related airway challenge by LTD4 (0.6 and 1.5 microgram/kg i.v.). Combined treatment with THEO 5 mg/kg + Ter 80 micrograms/kg resulted in an additive effect on RL and CDyn. The combination to THEO 20 mg/kg + TER 80 micrograms/kg was about as effective as THEO 20 mg/kg alone suggesting a nearly maximal effect by the latter treatment. It is concluded that THEO is considerably more efficient on the LTD4-induced airway obstruction than previously observed on the cholinergic model in guinea pigs. Combined treatment with THEO and beta 2-adrenoceptor agonist may antagonize in an additive manner the LTD4 effects on large and small airways. PMID- 2933566 TI - [Evaluation of cyproterone acetate in the treatment of hirsutism]. PMID- 2933567 TI - The effects of histamine and some related compounds on conditioned avoidance response in rats. AB - When histamine (Hi) and other agonists were applied intraventricularly, Hi caused a dose-dependent inhibition of the avoidance response in rats; its ED50 was 3.60 micrograms. 1-methylHi, 1-methylimidazole acetic acid and imidazole acetic acid which are major metabolites of Hi produced no inhibitory effect even at 50 micrograms. H1-agonists (2-methylHi and 2-thiazolylethylamine) also depressed the avoidance response; their dose-response lines run parallel to that of Hi. The depressant effects of H2-agonists (4-methylHi and dimaprit) were relatively weak; their dose-response lines were not parallel to that of Hi. When antagonists were pretreated intravenously, Hi action was clearly antagonized by diphehydramine and pyrilamine, but not by cimetidine or ranitidine. Intraventricular injection of Hi mixed with cimetidine or ranitidine did not change the effect induced by Hi alone. The avoidance response was not affected by noradrenaline, dopamine or 5 hydroxytryptamine. Although acetylcholine (ACh) suppressed the avoidance response dose-dependently, its effect was much weaker than that of Hi. Pretreatment with cholinergic blocking drugs (atropine and scopolamine) antagonized ACh action but not Hi action. From these results, it is assumed that the inhibitory effect of Hi on the avoidance response is preferentially linked to the H1-receptor. After intraventricular application of 3H-Hi, the highest radioactivity was determined in the hypothalamus. PMID- 2933568 TI - Calcium channel antagonist binding and pharmacology in rat uterine smooth muscle. AB - The calcium channel antagonists altered Ca-dependence of high K+-contractions of the estrogen dominant rat myometrium with the following pA2 values: PN-200-110, 10.63; nitrendipine, 9.56; nifedipine, 9.41; D-600, 9.05; and diltiazem, 7.57. Specific binding of 3H-nitrendipine occurred to the isolated plasma membrane vesicles with Kd of 0.1 to 0.3 nM and was inhibited by PN-200-110, nitrendipine, nifedipine and D-600, and slightly activated by diltiazem. The binding studies and the contractility studies were in excellent agreement for the three dihydropyridines, but not for D-600 and diltiazem. PMID- 2933569 TI - Simultaneous recording of dorsal raphe unit activity and serotonin release in the striatum using voltammetry in awake, behaving cats. AB - Simultaneous recordings of unit activity in the dorsal raphe nucleus (RD) and serotonin (5HT) release in the striatum were made in the cat. Unit recordings were made using Formvar-coated 32 microns diameter nichrome wires. 5HT release was measured using linear sweep voltammetry with semi-differentiation using electrodes prepared from Teflon-coated 32-gauge stainless steel wire filled with carbon paste and Ag/AgCl electrodes and 27-gauge stainless steel needles as reference and auxiliary electrodes, respectively. The working electrodes were scanned at a rate of 10 mV/s over the range of -0.1 to +0.5 V every 5 minutes using a BAS CV37 voltammograph. During REM sleep RD unit activity was decreased 94% from quiet waking (QW) baseline, while the voltammetric response was decreased by only 57%. Chloral hydrate anesthesia decreased RD unit activity by 18% from QW while the voltammetric response was decreased by 39%. LSD decreased RD unit activity by 50% from QW, but the voltammetric response was decreased by 88%. P-chlorophenylalanine produced no significant change in RD unit activity but decreased the voltammetric response by 82%. These data suggest that RD unit activity and 5HT release often differed dramatically. PMID- 2933570 TI - Workers' Compensation embraces psychiatry. PMID- 2933572 TI - Immune complex assays and their limitations. PMID- 2933571 TI - The role of iron in infection. PMID- 2933573 TI - [State of the neural elements of rabbit hair after irradiation and treatment with coamid]. PMID- 2933574 TI - Effects of strenuous exercise on myocardial blood flow. AB - Myocardial blood flow is the major determinant of oxygen delivery to the myocardium, since oxygen extraction by the myocardium is near maximum in the resting state. Regulation of flow during exercise depends on local metabolic factors and, to a small extent, on autonomic tone. Maximum flow of 5-6 times resting has been measured in reactive hyperemia experiments. In strenuous exercise, myocardial oxygen delivery appears to be adequate and flow reserve seems capable of handling the increased oxygen demand. No evidence of myocardial failure in normal hearts due to excess exercise has been presented. However, pulmonary hemorrhages found in horses after strenuous racing may be due to inadequate cardiac performance at maximal capacity. In humans, severe limitations to myocardial blood flow are imposed by coronary artery disease and by cardiac hypertrophy. In both cases regional myocardial ischemia may occur during the increased oxygen demands imposed by strenuous exercise. Individuals with coronary disease or cardiac hypertrophy are at risk for myocardial ischemia during exercise. Detection of myocardial blood flow abnormalities and ischemia during exercise has become an important goal in cardiac diagnosis. Prevention of serious or lethal consequence of strenuous exercise depends on a better understanding of the factors that regulate myocardial blood flow during ischemia. PMID- 2933576 TI - The guilt factor. PMID- 2933575 TI - Effects of chronic exercise on biochemical and functional properties of the heart. AB - This paper summarizes the effects of physical conditioning on the intrinsic biochemical and functional properties of the heart. The majority of studies reported to date have focused on the rat as an exercise model. Two general methods of training have been utilized: endurance running and swimming. Results collectively suggest that swimming enhances both intrinsic biochemical and functional properties of the rodent contractile system. The mechanism for inducing these adaptations remains unknown, but it could be due to the hypoxic environment of swimming. In contrast, endurance running programs involving rodents (as well as other species) suggest relatively little change in the biochemical and functional properties of the contractile system. Initial findings indicate that adaptation in calcium availability to the contractile system may be occurring to enhance cardiac performance in response to training. However, this adaptation, along with the possibility of contractile protein phosphorylation, needs to be examined in greater detail before definitive conclusions on cardiac adaptation can be reached. PMID- 2933577 TI - Spinal manipulation. PMID- 2933578 TI - [Pentachlorophenol: current knowledge]. PMID- 2933580 TI - The relationship of functional impairment & self-concept in the elderly with chronic illness. PMID- 2933579 TI - [Occupational allergic dermatitis: 5-year experience]. PMID- 2933581 TI - Coronary angioplasty for the treatment of acute myocardial infarction. PMID- 2933582 TI - Coordinate synthesis and degradation of the alpha-, beta- and gamma-subunits of the receptor for immunoglobulin E. AB - The surface receptor for immunoglobulin E (IgE) on rat basophilic leukemia cells and their normal counterparts has been postulated to consist of four polypeptide chains: a 45-kDa alpha-chain which binds IgE, a 33-kDa beta-component and two disulfide-linked, 9-10-kDa gamma-polypeptides. The instability of this complex in mild detergents makes it possible that, in vivo also, the structure may not be stable and that there is an independent assembly or exchange of the chains. We studied this question using surface-labeling and biosynthetic labeling techniques and found that the chains turn over coordinately and do not independently exchange. The results provide further support for the proposal that the alpha beta gamma 2 complex is the unit receptor for IgE. PMID- 2933584 TI - Adrenergic response to cardiopulmonary bypass. PMID- 2933583 TI - [Effect of long-term high-dose progesterone (Depo-Provera) therapy on endometrial carcinoma]. PMID- 2933586 TI - Nail biopsies in onychomycosis. PMID- 2933585 TI - A new ultraviolet-light sensitive mutant of Neurospora crassa with unusual photoreactivation property. AB - A mutant, uvs-(SA3B), which shows high sensitivity to UV light segregated among the progeny in a back-cross of a presumptive MMS-sensitive mutant to a wild-type strain. At 37% survival, this mutant was approximately 5 times more sensitive to UV and also 6 times more sensitive to 4-NQO than the wild type. But it was only slightly sensitive to gamma-ray, MMS, MNNG, MTC and histidine. It showed an unusual photoreactivation response. Its time course of photorecovery was similar to the photoreactivation-defective strain upr-1 of Neurospora crassa. Mutation induction by UV at the ad-3 loci in this mutant strain was lower than that at the same loci in the wild-type strain. The uvs-(SA3B) mutant maps between met-1 and col-4 in linkage group IV, and it was not allelic with the mutagen-sensitive mutant mus-8 which is located in this area. We have concluded, therefore, that uvs-(SA3B) has resulted from mutation in a new DNA-repair gene. This new mutant was barren in homozygous crosses. PMID- 2933587 TI - Plasma atrial natriuretic factor in patients with cirrhosis. PMID- 2933588 TI - A late-differentiation antigen associated with the helper inducer function of human T cells. AB - T lymphocytes possessing helper function produce soluble factors that greatly augment B-cell proliferation and differentiation into antibody-secreting cells. In humans the subset of T lymphocytes bearing the T4 surface antigen comprises most of the cells that display helper activity and recognize class II antigens of the major histocompatibility complex (MHC), while the subset bearing the T8 antigen comprises T cells recognizing class I MHC antigens and exhibiting cytotoxic or suppressor function. Monoclonal antibodies to T4 or T8 greatly inhibit the cognitive and effector function of cells with the corresponding phenotype. This function/phenotype correlation is not absolute, however, for there are many examples of T8-positive clones that recognize MHC class II antigens and have helper activity, as well as of T4-positive clones with suppressor or cytotoxic function. Recently a family of cell-surface neoantigens, which might be relevant to T-cell function and which are present on activated but not on resting T lymphocytes, has been identified in mouse and humans using monoclonal antibodies. Some of these antibodies block the cytolytic activity of alloreactive T-cell clones, suggesting the possible involvement of such molecules in the activation of cytotoxic T-cell clones or in the lytic process itself. We now describe a similar late-differentiation antigen (LDA1) that is expressed by human T lymphocytes only following activation and is recognized by a monoclonal antibody that inhibits the antibody-inducing helper function of T lymphocytes. PMID- 2933589 TI - Human blood platelets showing no response to collagen fail to express surface glycoprotein Ia. AB - The interaction of blood platelets with collagen is generally considered to be of primary importance in the arrest of bleeding and to have a role in the pathogenesis of thrombosis and atherosclerosis. Following damage to the vascular endothelium, circulating platelets come into contact with exposed collagen fibrils in the subendothelium and spread along it; this is followed by the secretion of several biologically active substances and by aggregation of platelets. The glycoproteins of the platelet plasma membrane have an important role in the mechanisms underlying these processes. So far, two specific defects of platelet function in patients with a bleeding disorder are known to be associated with a glycoprotein defect and the study of these patients has contributed significantly to present concepts of platelet function. The glycoprotein (GP) IIB-III complex, absent or deleted in the aggregation-defective Glanzmann's thrombasthenia, has been identified as the platelet fibrinogen receptor. GPIb, which is absent in the adhesion-defective Bernard-Soulier syndrome, has been identified as the von Willebrand factor receptor on platelets. We now report a defect of the platelet plasma membrane glycoprotein composition in a patient whose platelets are totally unresponsive to collagen. PMID- 2933590 TI - Identification of kinesin in sea urchin eggs, and evidence for its localization in the mitotic spindle. AB - To understand the molecular basis of microtubule-associated motility during mitosis, the mechanochemical factors that generate the relevant motile force must be identified. Myosin, the ATPase that interacts with actin to produce the force for muscle contraction and other forms of cell motility, is believed to be involved in cytokinesis but not in mitosis. Dynein, the mechanochemical enzyme that drives microtubule sliding in eukaryotic cilia and flagella, has been identified in the cytoplasm of sea urchin eggs, but the evidence that it is involved in cytoplasmic microtubule-based motility (rather than serving as a precursor for embryonic cilia) is equivocal. Microtubule-associated ATPases have been prepared from other tissues, but their role in cytoplasmic motility is also unknown. Recent work on axoplasmic transport, however, has led to the identification of a novel mechanochemical protein called kinesin, which is thought to generate the force for moving vesicles along axonal microtubules. These results suggest that kinesin may also be a mechanochemical factor for non axoplasmic forms of microtubule-based motility, such as mitosis. We describe here the identification and isolation of a kinesin-like protein from the cytoplasm of sea urchin eggs. We present evidence that this protein is localized in the mitotic spindle, and propose that it may be a mechanochemical factor for some form of motility associated with the mitotic spindle. PMID- 2933592 TI - [Sensitization due to chloramphenicol]. PMID- 2933591 TI - Biochemical and behavioral changes in rats after prolonged treatment with desipramine: interaction with p-chlorophenylalanine. AB - The decrease in the Bmax value of 3H-dihydroalprenolol (3H-DHA) binding to cortical membranes of rat brain induced by long-term administration of desipramine (DMI) was prevented by concomitant treatment with parachlorophenylalanine (pCPA). Acute administration of DMI significantly decreased locomotor activity in saline- and (pCPA)-pretreated rats. DMI-induced inhibition of locomotor activity was abolished in (pCPA)-pretreated rats chronically treated with DMI. Conversely, in pCPA-pretreated animals, acute DMI could still significantly decrease the locomotion of chronically DMI-treated rats. The data presented indicate that an intact serotoninergic system is required to enable antidepressant drugs to induce biochemical and behavioral changes following their chronic administration. PMID- 2933593 TI - Hepatitis B vaccine for the family physician. PMID- 2933594 TI - [Value of palpation and auscultation in stenoses and occlusions of the carotid arteries]. PMID- 2933595 TI - Cerebral metabolism in hyper- and hypocarbia: 31P and 1H nuclear magnetic resonance studies. AB - Paralyzed rabbits ventilated with an oxygen, nitrous oxide, and carbon dioxide mixture were subjected to hyper- and hypocarbic stress. An Oxford Instrument TMR 32-200 spectrometer was used to record phosphorus-31 and nonwater proton nuclear magnetic resonance spectra of the in vivo brain. These spectra provide measurements of cerebral pHi, phosphocreatine, orthophosphate, ATP, and lactate. The brain exhibited twice as much acute pH-regulating ability as the arterial blood. During hypercarbia, orthophosphate rose while phosphocreatine declined in a reciprocal manner, and ATP remained constant. During hypocarbia, lactate rose gradually over a period of 1 hour, while orthophosphate, phosphocreatine, and ATP remained constant and calculated values of adenosine mono- and diphosphate rose. PMID- 2933596 TI - [Spinal nociceptive reflex response. Changes in the RaIII nociceptive reflex response and in lumbo-sciatic pain induced by transcutaneous electric nerve stimulation and vibrations]. PMID- 2933597 TI - [Nitrendipine, a new calcium antagonist, in the therapy of arterial hypertension]. AB - Bay e 5009 (nitrendipine) is a new calcium-antagonist that acts mainly on blood vessel smooth muscles. The effects of this drug on hypertensive patients of both sexes was investigated. Nine patients were treated for 42 days at a fixed dosage of 1 tablet/day. A highly significant fall in arterial pressure was obtained (p less than 0.001). Seven patients took 20 mg/day of nitrendipine for 14 days and a significant reduction in A.P. was obtained (p less than 0.001): for the next four weeks, the dosage was increased to 20 mg twice a day when a further decrease in systolic and diastolic A.P. was obtained without the occurrence of side effects. A further five patients were treated for 14 day (20 mg/day). These showed a fall in blood pressure levels (p less than 0.001) but suffered from slight oedema which made it necessary to suspend the treatment. An increase in heart rate was noted in all patients (p less than 0.001). This was due to reflex adrenergic activation. Nitrendipine therefore proved effective as an antihypertensive drug even at a daily dose of only 20 mg. PMID- 2933598 TI - [Skin pathology caused by drugs]. AB - 175 patients suffering from acute drug-induced skin pathologies were examined with particular reference to age of onset, clinical type and causative agent. The most common pathology was urticaria, followed by eczematous and exanthematic eruptions. The drugs most frequently responsible for such reactions were the analgesic-antipyretic-anti-inflammatory group, topical products and antibiotics. These data are discussed in detail. PMID- 2933599 TI - [Hematoma of the rectus abdominis muscle as cause of diagnostic error in obstetrics]. PMID- 2933600 TI - Adolescence and physical handicap. PMID- 2933602 TI - Identification of chorion villi in abortion specimens. AB - The incidence of ectopic pregnancy is rising. All patients with a diagnosis of spontaneous abortion should be observed until they have been proved not to have an ectopic pregnancy. To help in identifying patients with an ectopic pregnancy, sensitive human chorionic gonadotropin tests, ultrasound, and laparoscopy have been used, yet there has been a tendency to forget the simple method of looking for chorion villi. In material specimens of 272 patients with the initial diagnosis of spontaneous abortion, the gynecologist could identify villi in 50% and the pathologist could identify another 30%. Thus, only 20% had to be observed by other methods and one-third proved to have an ectopic pregnancy. PMID- 2933601 TI - Acne fulminans with severe myalgia precipitated by isotretinoin therapy. PMID- 2933604 TI - Audiometers should be tested daily as part of industry hearing program. PMID- 2933603 TI - Poor building designs hinder safe emergency escape by handicapped. PMID- 2933605 TI - Manufacture and clinical application of XZY-1 model computer assisted ECG automatic diagnosis system. PMID- 2933606 TI - [Hygiene in public health clinics]. PMID- 2933607 TI - [Obesity and atherosclerosis as specific toxic alcohol sequelae]. PMID- 2933608 TI - [Blood pressure measurements in mass screening and epidemiologic studies--does use of random zero instruments bring advantages?]. PMID- 2933609 TI - [Subjective health in an urban population]. PMID- 2933610 TI - [Examination of kindergarten and school children by the public health department (development and content of a questionnaire)]. PMID- 2933611 TI - [Psychosocial services of the city of Herne 1980-1984]. PMID- 2933612 TI - [Performance and cost transparency in legal health insurance--a model trial in the Heilbronn district]. PMID- 2933613 TI - [Dental care of German deep-sea fishermen]. PMID- 2933614 TI - [Current status and future of cooperation between physicians and social insurance and their partners from the hospital and general practice. Daily practice: problems and their solution]. PMID- 2933615 TI - [Sense or nonsense of inpatient "cures" in liver disease patients--2]. PMID- 2933616 TI - [Activity of biological oxidation enzymes in the blood of children at different stages of development and with different dynamics of myopia]. PMID- 2933617 TI - Hormonal treatment of disseminated male breast cancer. AB - 14 males with disseminated cancer of breast received a total of 35 endocrine trials, mainly in the form of hormonal supplementation. Overall, a 43% response rate was observed. In particular, remissions occurred in 7 of 11 instances with cyproterone acetate, in 3 of 7 with tamoxifen, in 2 of 5 with estrogens, in 2 of 5 with aminoglutethimide, in none of 3 with high-dose medroxyprogesterone acetate, in none of 1 with androgens, and in 1 of 3 with castration. The response to additive hormonal therapy was 44%. Median overall response duration was 10 months, 11 months following additive hormonal therapy. Median survival from start of therapy was longer in responding than in nonresponding patients (23.5 vs. 11 months). A disease-free interval did not appear to influence hormonal response. Patients responding to one form of hormonal treatment had a greater likelihood of responding to subsequent hormonal manipulations. Additive hormonal therapy may provide effective palliation in males with advanced breast cancer, and should be considered as a valid alternative to orchiectomy. PMID- 2933619 TI - Antioxidant modulation of phacoanaphylactic endophthalmitis. AB - Catalase treatment reduces the expected inflammation in experimental phacoanaphylactic endophthalmitis. Catalase is a scavenger of hydrogen peroxide and presumably protects against the cytolytic effects of reactive oxygen metabolites. Recent work indicates that oxygen-derived free radicals may play a critical role in the early tissue damage in immune complex disease. PMID- 2933618 TI - Alloantigen-activated lysis of syngenic tumor augmented by allogenic lymphocytes as cold targets. AB - In the past, most work in tumor immunology involved attempts to demonstrate tumor specific transplantation antigens; however, recent in vitro work has shown that it is not necessary to sensitize to a specific tumor antigen to achieve lysis of syngenic tumor cells. Responder spleen cells from B6AF1 mice (H-2a,b) were sensitized in mixed lymphocyte cultures (MLC) to alloantigens on spleen cells from B10.D2 (H-2d) mice. In cell-mediated lympholysis (CML) assays the relevant allogenic P815 (H-2d) tumor targets and B10.D2 lymphoblast targets were lysed. In addition, the semisyngenic tumor target EL-4 (H-2b) was lysed but RDM-4 (H-2k) was not. B10.BR (H-2k), C57BL/6 (H-2b) and B6AF1 lymphoblasts were not lysed. If lymphocytes were added as cold targets to the CML assay, B10.D2 lymphocytes completely absorbed lytic activity when B10.D2 lymphoblasts were the target. If B10.D2 lymphocytes were added when P815 was the target, lysis was reduced but could not be abolished. When B10.D2 lymphocytes were added with EL-4 as a target, lysis doubled. These experiments show that the neoplastic determinant on tumor cells recognized by alloantigen-activated lymphocytes does not cross-react with stimulator cell alloantigen and is not an alien histocompatibility antigen. These observations should be considered when in vivo attempts are made to control tumor with in vitro activated lymphocytes; transfer of not only in vitro activated cells but also allogenic stimulator cells to the tumor site may be necessary for maximal tumor destruction. PMID- 2933620 TI - [Data for predicting road-transport injuries]. PMID- 2933621 TI - [Systemic basis of organization of the process of rehabilitation of traumatological-orthopedic patients]. PMID- 2933622 TI - [Current results of hemostasis research (protein C, protein S) and their effect on oral anticoagulant therapy in clinical practice]. PMID- 2933623 TI - The role of compensation in chronic pain: analysis using a new method of scoring the McGill Pain Questionnaire. AB - Patients who receive worker's compensation or are awaiting litigation after an accident have long been regarded as neurotics or malingerers who are exaggerating their pain for financial gain. However, there is a growing body of evidence that patients who receive worker's compensation are no different from patients who do not. In particular, a recent study found no differences between compensation and non-compensation patients based on pain scores obtained with the McGill Pain Questionnaire (MPQ). Since the MPQ is usually scored by using rank values rather than more complex scale values, the negative finding might be attributable to the loss of information by using rank values. Consequently, a simple technique was developed to convert rank values to weighted-rank values which are equivalent to scale values. A study of 145 patients suffering low-back and musculoskeletal pain revealed that compensation and non-compensation patients had virtually identical pain scores and pain descriptor patterns. They were also similar on the MMPI pain triad (depression, hysteria, hypochondriasis) and on several other personal that were examined. The only differences were significantly lower affective or evaluative MPQ scores and fewer visits to health professionals by compensation patients compared to non-compensation patients. These results suggest that the financial security provided by compensation decreases anxiety, which is reflected in the lower affective or evaluative ratings but not the sensory or total MPQ scores. Compensation patients, contrary to traditional opinion, appear not to differ from people who do not receive compensation. Accidents which produce injury and pain should be considered as potentially psychologically traumatic as well as conducive to the development of subtle physiological changes such as trigger points. Patients on compensation or awaiting litigation deserve the same concern and compassion as all other patients who suffer chronic pain. PMID- 2933624 TI - Comprehensive assessment of chronic low back pain patients and controls: physical abilities, level of activity, psychological adjustment and pain perception. AB - A comprehensive functional evaluation designed for patients with chronic low back pain (CLBP) is described. The evaluation includes measures from 4 domains of the CLBP syndrome; physical abilities, level of activity, psychological adjustment and pain perception. New measures for standardized assessment of physical abilities and employment of body mechanics are introduced. Evaluation data from 68 CLBP subjects and 35 age-matched, pain-free, controls is presented. Results indicate important deficits in physical abilities and psychological adjustment for the CLBP group compared to the controls. Factor analysis of the evaluation measures yielded a general conditioning factor and a general psychological adjustment factor but complicated factor structures for report of pain and time in activities. Further analysis demonstrated a strong relationship between objective disability and psychological and psychosocial adjustment but little relationship between level of pain and other disability measures. PMID- 2933625 TI - Prolactin and cortisol responses to the experience of low back pain. AB - Demographic, clinical and psychological characteristics of 92 patients with low back pain were correlated with prolactin and cortisol levels in cerebrospinal fluid (CSF). Somatization and depression scores correlated statistically significantly with the CSF serum ratio of prolactin both in men and in the total group. An increased CSF/serum ratio of cortisol was slightly associated with somatization scores in the total group. Multiple stepwise regression, furthermore, revealed that somatization, anxiety and one of the pain indices contributed to the variance in the CSF prolactin level, which was mostly dependent on the respective serum level. Sex and electromyographic findings (EMG) accounted for 12 and 7%, respectively, of the variance in the afternoon cortisol levels. Women reported more somatization and depression feelings than did men. Most of the data support our earlier assumption that male and female pain patients have different coping mechanisms. In spite of the common underlying endocrine responses to distress in men and women, gender differences in psychological response appear to modify endocrine responses to the experience of low back pain. PMID- 2933626 TI - A comparison between the MMPI and the 'Mensana Clinic Back Pain Test' for validating the complaint of chronic back pain in women. AB - Reports on the efficacy of the Minnesota Multiphasic Personality Inventory (MMPI) for selecting patients with valid complaints of pain, have been equivocal. The Mensana Clinic Screening Test for Chronic Back Pain Patients (MPT) was able to predict, with some degree of success, patients who had definite organic pathology. However, ther MMPI measures personality traits, while the MPT measures the impact of pain on a patient's life. In order to determine which of the two tests would be a better predictor of actual physical abnormalities, and hence valid pain complaints, a comparison was undertaken between the two tests. The charts of 53 female admissions to the Neurosurgery Service of Johns Hopkins Hospital, with the complaint of back pain, were assessed. MMPI test results, as well as test results for the MPT, were compared to the presence or absence of pathology on electromyography, nerve conduction velocity studies, thermography, myelogram, CT scan, or X-ray. The MPT had a correlation factor of -0.5384, that was significant at the 0.00002 level. Of the 30 patients scoring 17 points or less on the MPT, 77% had objective physical abnormalities, considered moderate or severe by blind review. Of the 23 patients scoring 18 points or greater on the MPT, only 18% had objective physical findings that were considered moderate or severe. Only the depression scale (scale no. 2) of the MMPI correlated with objective physical abnormalities (R = -0.30). However, only 58% of the patients with T scores on scale no. 2 of less than 70 had objective findings, while 56% of patients with T scores greater than 70 had objective physical findings.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2933627 TI - Contrast medium cause the apparent increase in beta-endorphin levels in human CSF following brain stimulation. PMID- 2933628 TI - The (non)sense of the present-day classification system of sports for the disabled, regarding paralysed and amputee athletes. AB - In order to guarantee fair competition amongst athletes, suffering from spinal paralysis with different neurological levels, a classification-system on a medical basis was introduced at the beginning of the annual Stoke Mandeville Paraplegic Games in the 1950s. The system was set up in such a way, that athletes with comparable degrees of disability were put together in the same class, in principle not depending on the actual sporting events. Subsequently a similar system was introduced for amputee athletes, and this system is still being used. In view of the large number of competitors, the Olympic Games for the Disabled in 1980 in the Netherlands were the basis for a statistical research analysis on the acquired data, studying the results of competition in connection with the medical classification data. The following types of sports were looked at: athletics, swimming, archery and weight-lifting. The objective was, to justify the (theoretical) medical classification-system by means of (practical) actual figures (results of competition). As a basic method the 'zero-hypothesis' has been used. Specifically the 'Student's t distribution' has been used in view of the small samples. The interim conclusion is, that the present-day classification system is good with regards to those with poliomyelitis, and to tetraplegic and paraplegic sports people both with complete or incomplete lesions competing together, but the number of classes requires to be diminished in several sports events. The same research analysis of the results of the Olympic Games for the Disabled of 1984 will be made in order to compare the two studies and to make final conclusions. PMID- 2933629 TI - Giardia muris-induced depression of the primary immune response in spleen and mesenteric lymph node cell cultures to sheep red blood cells. AB - Primary in vitro plaque-forming cell (PFC) responses to sheep red blood cells (SRBC) were examined for spleen and mesenteric lymph node (MLN) cell populations from susceptible (A/J) and resistant (B10.A) mice during the infection with Giardia muris. Spleen and MLN cells isolated from mice during the acute phase of the infection were less responsive to SRBC in vitro than those from uninfected mice. Depressed anti-SRBC PFC response was detected earlier and was more pronounced in MLN cell cultures when compared to the response of spleen cell cultures. Spleen and MLN cells from donors infected with G. muris for 15 days had the capacity of depressing PFC response to SRBC of cells isolated from uninfected mice. This suppressor activity was localized in the plastic-adherent fraction of spleen cell populations isolated from A/J and B10.A mice. Since G. muris is a gastro-intestinal infection of mice, lower capacity of the MLN cells to respond to an antigenic stimulation in vitro may explain, in part, the proliferation of the trophozoites during the acute phase of the infection. PMID- 2933630 TI - Platelet mediated killing of larvae from different filarial species in the presence of Dipetalonema viteae stimulated IgE antibodies. AB - The platelets from normal rats interact with microfilariae of Dipetalonema viteae in vitro in the presence of antibodies leading to the killing of the parasite. The antibody involved in this reaction is identified as IgE because the absorption of immune rat serum on anti-rat IgE column or the pretreatment of platelets with anti-Fc epsilon receptor resulted in a significant reduction in the percentage of killing of microfilariae. This antibody, which mediates platelet activity towards microfilariae, appears early in the secondary infection and persists for a short period of time. This short-lasting IgE antibody is not apparently present in the form of large complexes since the supernatant but not the pellet after ultracentrifugation was able to mediate killing of microfilariae by platelets. IgE-dependent platelet-mediated parasite killing is neither stage- nor species-specific because the microfilariae (LI) of Brugia malayi or of Loa loa and infective larvae (L3) of D. viteae or of B. malayi were killed when they were incubated with the serum obtained from rats at day 8 after secondary infection with adult D. viteae worms. The results of the present study suggest that platelets can actively participate in the immunological killing of filarial larvae. PMID- 2933631 TI - Therapeutic catheter procedures in pediatrics. AB - There is a large spectrum of interventional catheter procedures being performed presently in children. The procedures that offer a greater advantage than surgical techniques and that will continue to be established procedures include percutaneous angioplasty of the pulmonary valve, peripheral pulmonary artery and caval stenosis, embolizations of pulmonary collaterals and pulmonary arteriovenous malformations, angioplasty of vascular access shunt, embolization of bronchial arteries for hemoptysis, and percutaneous nephrostomy and abscess drainage procedures. Others that have been successful but not yet routinely established in children include thrombolysis, renal artery angioplasty, embolization of peripheral arteriovenous malformations, dilatation of the urinary and gastrointestinal tract stenosis, and percutaneous biopsy. PMID- 2933632 TI - Prenatal diagnosis of GM2 gangliosidosis with high residual hexosaminidase A activity (variant B1; pseudo AB variant). AB - A case of infantile GM2 gangliosidosis with high residual beta-hexosaminidase A activity toward the synthetic substrate 4-methylumbelliferyl-2-acetamido-2-deoxy beta-D-glucopyranoside was diagnosed prenatally. Extracts from cultured amniotic fluid cells of the fetus had a hexosaminidase A activity of 27% of total hexosaminidase but were almost completely unable to degrade [3H]ganglioside GM2 (less than 0.5% of control values) when assayed in the presence of the natural activator protein. These results were confirmed by analyses of fetal muscle fibroblasts, liver, and brain. All tissues examined showed a profound deficiency of ganglioside GM2 galactosaminidase despite hexosaminidase A levels in the heterozygote range. In brain tissue, ganglioside GM2 content was elevated more than 4-fold. Hydrolysis of p-nitrophenyl glucosaminide-6-sulfate, a substrate specific for hexosaminidases A and S, by tissue extracts was also markedly reduced but the residual activities found (5% in liver, 12% in fibroblasts, and 16% in brain) were much higher than those with the physiological lipid substrate, ganglioside GM2. PMID- 2933633 TI - Synthesis and radioreceptor binding activity of N-0437, a new, extremely potent and selective D2 dopamine receptor agonist. AB - The synthesis of a new, potent and selective D2 dopamine receptor agonist, N 0437, of the 2-aminotetralin group is described. The results of a radioreceptor binding assay using a homogenate of porcine anterior pituitary as a tissue source for D2 dopamine receptors and 3H-spiperone as radioligand demonstrate that this compound is one of the most potent compounds so far evaluated in this test system. PMID- 2933635 TI - Detection of sub-picogram quantities of specific DNA sequences on blot hybridization with biotinylated probes. AB - A sensitive method for detecting biotinylated DNA probes on dot and Southern blots is described which is based on the principle outlined by Leary et al (1). This system has two main components: detection of biotinylated DNA by a two-step procedure with streptavidin and poly(alkaline phosphatase); and blocking background with Tween 20. 32fg and 80fg of lambda phage DNA was detected on dot and Southern blot hybridizations respectively. 150fg of beta-globin was detected on Southern blots of genomic DNA. This method is fast, reproducible and can detect single copy genes in 0.25 micrograms genomic DNA on Southern blots. PMID- 2933634 TI - A primer vector system that allows temperature dependent gene amplification and expression in mammalian cells: regulation of the influenza virus NS1 gene expression. AB - Influenza virus RNA segment 8 has been cloned into primer-vector pSLts1. This vector was designed to replicate in simian cells in a temperature dependent fashion by use of the SV40 tsA209 T-antigen gene. The oriented synthesis of cDNA on dT-tailed pSLts1 was performed on in vitro synthesized mRNA, and the second DNA strand was primed with an influenza-specific terminal oligodeoxynucleotide. Recombinant pSLVa232 contained the RNA segment 8 sequence directly fused to the SV40 late promoter contained in pSLts1, and followed by the SV40 polyadenylation signal. Expression of NS1 gene in transfected COS cells took place at a level comparable to that found in infected cells. When VERO cell cultures were transfected with recombinant pSLVa232, expression of the NS1 gene was temperature dependent. Close to one hundred fold increase in the amplification and expression of the cloned gene was observed after shift down of the transfected cells to permissive temperature. Vector pSLts1 and the cloning strategy described may be useful for the specific cloning and regulated expression of mRNAs of known 5' terminal sequence. PMID- 2933636 TI - An RFLP associated with the human catalase gene. PMID- 2933637 TI - RA can alter the distribution of ATPase-positive Langerhans cells in the hamster cheek pouch in association with DMBA application. AB - Thirty-six young adult male and female Syrian hamsters were divided into four groups. Group 1 (N = 6) was treated with mineral oil, Group 2 (N = 12) was treated with 7,12-dimethylbenz[a]anthracene (DMBA), Group 3 (N = 12) was treated with DMBA and 13-cis-retinoic acid (RA), and Group 4 (N = 6) was treated with RA only. The hamsters were treated three times a week for six weeks. When the DMBA treated animals were also treated with RA, tumor formation was inhibited. In the DMBA-treated animals that did not have RA, there was a significant reduction in the number of Langerhans cells (LCs) located interfocally and in foci compared with controls (p less than or equal to 0.001). The systemic administration of 10 mg of RA significantly increased the number of ATPase-positive LCs in the focal aggregates (p less than or equal to 0.001). Interfocally, the number of ATPase positive LCs was statistically elevated in pouches from RA- and DMBA-treated animals (Group 2 vs. Group 3, p less than or equal to 0.01). Following the administration of RA (Group 4), there was a statistically significant increase of LCs interfocally compared with Groups 2 or 3 (p less than or equal to 0.001). RA administered alone resulted in a small increase in foci compared with Group 3 but in a significant decrease compared with the control group (p less than or equal to 0.001). Systemic RA appears to not only affect the number of ATPase-positive LCs but also to alter the distribution of these cells in DMBA-treated pouches.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2933638 TI - Medical/dental management of a patient with congenital Factor XIII. PMID- 2933639 TI - Experimental dissociation of food intake and plasma beta-endorphin following 2 deoxy-D-glucose in rats. AB - The present studies were undertaken to further assess the role of plasma beta endorphin (beta-EP) in the hyperphagia induced by the glucose antimetabolite, 2 deoxy-D-glucose (2-DG). Plasma concentrations of immunoreactive beta-EP (ir-beta EP) were measured at the end of the first hour of feeding in all animals treated with 400 mg/kg 2-DG. Previous studies had shown a consistent, positive association between 2-DG hyperphagia and plasma ir-beta-EP concentrations, but the present data revealed dissociations between hyperphagia and plasma ir-beta EP. Dexamethasone administration blocked the 2-DG-induced rise in plasma ir-beta EP, but had no effect on the 2-DG hyperphagia measured at 1 hour. Forced drinking of a 2% NaCl solution decreased 2-DG hyperphagia, but not the 2-DG induced rise in plasma ir-beta-EP. Thus, elevations in plasma ir-beta-EP are not necessary for the full expression of 2-DG-induced hyperphagia in dexamethasone-treated rats. Furthermore, decreased feeding responses to 2-DG could coexist with increased levels of plasma ir-beta-EP in NaCl-treated normal rats. Elevations in plasma ir beta-EP do not appear to be the critical opiate link in 2-DG induced hyperphagia. PMID- 2933640 TI - Relaxant activity of atriopeptins in isolated guinea pig airway and vascular smooth muscle. AB - Atriopeptins are circulating peptide hormones which are secreted by atrial tissue and act at the kidney. Because the atriopeptins survive passage through the pulmonary circulation, they also may be involved in the modulation of airway or pulmonary vascular smooth muscle tone. Using in vitro organ bath techniques, atriopeptins were found to induce potent concentration-dependent relaxation of isolated guinea pig trachea, and pulmonary artery with a rank order of potency: atriopeptin III greater than atriopeptin II greater than atriopeptin I. Atriopeptin-induced smooth muscle relaxation was observed to be a direct response since it was not mediated by activation of relaxant VIP receptors, beta adrenergic receptors, or H2 receptors nor affected by cyclooxygenase inhibition or denuding of the vasculature or trachea of endothelial and epithelial cells. The time course of atriopeptin II-induced relaxation of the pulmonary artery was transient in contrast to the prolonged relaxations on the trachea. The transient relaxant responses of atriopeptin II on pulmonary artery were not due to metabolism of atriopeptin II to atriopeptin I by angiotensin-converting enzyme since pretreatment with captopril did not augment the response. These results seem to indicate that distinct atriopeptin receptors may exist in airway and pulmonary arterial smooth muscle and that activation of these relaxant receptors may play an important role in the regulation of pulmonary vascular and bronchomotor tone. PMID- 2933641 TI - [Diagnostico-therapeutic algorithm in the lumbosacral pain syndrome]. PMID- 2933642 TI - Percutaneous transluminal coronary angioplasty: morphological findings in 3 patients. AB - Little morphologic information is available on the status of the major epicardial coronary arteries in patients dying after percutaneous transluminal coronary angioplasty. We studied hearts from 3 men (aged 60, 45 and 47 years) dying 3 days, 1 month and 7 months after balloon--dilatation of obstructed coronary artery segments. Twice the left anterior, once the left main coronary artery have been desobliterated. In one patient the procedure has not been successful and a venous bypass graft had to be implanted. Histologically the site of dilatation is clearly recognisable after 7 months. The characteristic findings are intimal tears in the segment opposite to the obstructing plaque. The intimal gaps are filled after 7 months by a neointima. In the dilated left main coronary we find 1 month after angioplasty an extensive proliferation of smooth muscle cells resulting in restenosis. Two patients died suddenly after an interval without angina. In the third patient--ome hours after bypass grafting--spasm of the non involved right coronary artery occurred resulting in inferior infarction; this patient died 3 days after dilatation. PMID- 2933643 TI - Stiff skin syndrome. AB - Stiff skin syndrome was first documented by Esterly and McKusick. We saw a patient with this disease, as well as another who had a similar condition but a somewhat different histology. These two patients shared heritable stiff skin, restricted joint mobility, and absent mucopolysacchariduria. In stiff skin syndrome, which may have two variants, skin biopsy demonstrates large cells stained metachromatically by toluidine blue. These cells are shaped like dermal melanocytes or rounded cells and their presence may be directly related to the deposition of mucopolysaccharide in the dermis. In some cases they may invade the deeper tissues. Two cases of stiff skin syndrome that were in the Japanese literature are also discussed. PMID- 2933644 TI - Pelvic inflammatory disease. PMID- 2933645 TI - Prenatal diagnosis for Tay-Sachs disease using chorionic villus sampling. AB - Prenatal diagnosis for Tay-Sachs disease was performed on 25 patients using chorionic villus sampling (CVS). Nineteen were diagnosed as normal, and six were affected. Normal villus extracts had both hexosaminidase (hex) A and B activity, as determined by Cellogel and polyacrylamide gel electrophoresis, while extracts from affected fetuses had only hex B activity. Compared to cultured amniotic fluid cells or fibroblasts, villi contained less hex A. Hex A levels in fresh villi and cultured trophoblasts were roughly comparable. PMID- 2933646 TI - [Current concepts of autoimmune polyendocrinopathies]. PMID- 2933647 TI - [Obstructive anuria with non-dilated cavities]. AB - Four patients with no evidence of acute functional or organic renal failure suddenly developed anuria. Repeated ultrasonographic exploration failed to show any dilatation of the urinary tract. After 4, 5, 7 and 34 days of anuria respectively, an obstacle was detected, located and identified by ultrasonically guided antegrade pyelography, which led to immediate urine derivation by percutaneous nephrostomy. Three of these patients were cured by percutaneous techniques alone. These 4 cases represent a small but not negligible part of a series of 74 patients with obstructive anuria, 70 of whom had dilated renal cavities. They throw doubt not on the reliability of ultrasonography, but on the idea that all obstacles are associated with dilatation upstream. They also confirm that opacification of the urinary tract is the only way of making sure that an obstacle is present. Antegrade pyelography gives excellent contrast images and can be used as first stage of a percutaneous nephrostomy. The other diagnostic methods are fraught with a high proportion of inadequacy or failure. PMID- 2933648 TI - [Malignant lymphoma of the testis]. AB - The incidence of non-Hodgkin's lymphoma of the testis is in the order of 1.8% in adults. Ten cases of lymphomas histologically proven after orchidectomy are reported: 5 were diffuse large cell, 4 immunoblastic and 1 diffuse small cell lymphomas. Mean age was 56 years. Five patients had stage IE or IIE and 5 stage IV disease after staging. Seven patients had received chemotherapy followed by subdiaphragmatic irradiation and 2 with localized lymphoma were treated by radiotherapy alone after orchidectomy. Four patients in remission relapsed after 6 to 24 months. Central nervous system involvement during the course of the disease was observed in 5 cases. Five patients are still alive in remission after an 18 to 80 months follow-up. PMID- 2933649 TI - [Tumoral hypophosphoremic osteomalacia]. AB - Various tumoral diseases may induce hypophosphataemic osteomalacia. This is the case, in particular, with mesenchymal tumours and sclerosing metastases of prostatic cancer; much less common causes are diffuse connective tissue dysplasias and non-prostatic epitheliomas. Depending on whether osteomalacia results from a mesenchymal tumour or from osteitis of prostatic origin, the practical problems encountered are quite different. In the first case, the important point is not to miss a mesenchymal tumour when confronted with an acquired and apparently idiopathic hypophosphataemia; repeated examinations at regular intervals are sometimes necessary to detect the tumour which is usually benign; osteomalacia can then be cured by its removal. In the second case, the difficulty is to detect an osteomalacia which may be masked by bone metastases and to recognize its tubular origin in order to prescribe the appropriate treatment. Little is known about the pathogenesis of tumoral hypophosphataemic osteomalacia. The renal diabetes and low 1,25 (OH)2 D plasma levels frequently associated with the disease reflect a complex enzymatic disorder thought to be caused by a humoral mediator secreted by the tumour. Studies carried out in this field have already shown that 1,25 (OH)2 D is therapeutically useful when the tumour cannot be excised. PMID- 2933650 TI - [Suture of a carotid arteriotomy over a dilator]. AB - Using a conical dilator as support during closure of arteriotomy improves the caliber of the vessel and makes its wall much more regular. This improvement has been confirmed by routine per-operative arteriography. PMID- 2933651 TI - [Desensitization of allergic diseases: new allergens, increased vigilance]. PMID- 2933652 TI - [Increase in hepatic arterial pressure during hepatic intra-arterial chemotherapy]. PMID- 2933653 TI - [Myelolipoma of the adrenal gland. Preoperative diagnosis is now possible]. PMID- 2933655 TI - [Retraction of the branches of Greenfield's intracaval filter. An indirect sign of thrombosis of the inferior vena cava]. PMID- 2933654 TI - [Idiopathic retroperitoneal fibrosis associated with Riedel's thyroiditis]. PMID- 2933656 TI - [Methemoglobinemia and acute toxic hemolytic anemia caused by gingival lotion with a benzocaine and resorcinol base]. PMID- 2933657 TI - [Reappraisal of the water test in adrenocortical exploration]. AB - The water-loading test (Robinson's test) has been used since 1941 to evaluate the adrenocortical function. Due to this technique, impaired water excretion has become a classical feature of adrenal deficiency. The purpose of this study was to assess the reliability of this test when compared with modern procedures for adrenal exploration. Water excretion was decreased in 23 cortisol-deficient patients but also in 16 out of 58 subjects (27%) with normal adrenal biological tests. We consider that this simple test, although old-fashioned, remains useful since normal diuresis after 2 hours is sufficient to rule out a cortisol deficiency. PMID- 2933658 TI - [Lymphocytic interstitial pneumopathy and primary pulmonary lymphoma. Differential diagnosis]. AB - Two cases of lymphoid interstitial pneumonia, diagnosed according to Liebow's criteria, are reported. In both cases an extra-thoracic lymphoma developed 3 and 6 years respectively after the interstitial pneumonia was diagnosed. Simultaneously, the radiological images of the lungs became more pronounced. Only a few similar cases have been published. This raises the question of whether lymphoid interstitial pneumonia and lymphomas are distinct entities, especially since the histological and immunopathological discriminating criteria seem to be discussed. PMID- 2933660 TI - [An original technic for closure of a postinfarction interventricular communication]. AB - An original technique has been successfully used to treat a case of major interventricular communication consecutive to a recent, wide antero-septo-apical infarction. This technique derives directly from Guilmet's reconstructive aneurysmoplasty used for chronic fibrous aneurysms of the left ventricle. The distended anterior aspect of the left ventricle was resected, the left border of the ventriculotomy was lowered and attached to the healthy part of the septum and the right border was brought over and sutured to the lateral aspect of the ventricle. The interventricular communication was therefore closed and excluded from the left ventricular cavity, thus theoretically reducing the risk of residual shunt. The post-operative period was uneventful. PMID- 2933659 TI - [Hepatic metastases. Medicosurgical treatment or priority to surgery?]. AB - Not all patients with liver metastases should be referred to the surgeon. Selection is necessary, based on the patient's general and hepatic condition, on the nature of the primary cancer and on the intra-hepatic spread of the metastases. At the moment, less than 1% of patients with metastatic liver are operated upon. In the absence of clinical or biochemical evidence of hepatic dysfunction, surgical specialists may consider operating patients under 75 with synchronous or metachronous metastases from colorectal cancer or endocrine tumours. If clinical and laboratory evaluation is favourable, the decision to operate and the type of partial hepatic resection selected depend on pre operative investigations which are, successively: ultrasonography, computerized tomography, radioisotope scanning and possibly arteriography for endocrine tumours (not all these examinations are necessarily required). Other possible referrals are patients with liver metastases from non-colorectal or non-endocrine primary tumours of low evolutive potential, as evaluated by changes in levels of biological markers and by monthly morphological studies of metastatic tissue over 3 to 6 months. The major limiting factor in these patients is previous heavy chemotherapy which makes this type of surgery extremely hazardous. Recently published data justify primary surgical reduction of the tumour followed by systemic or regional chemotherapy at the end of the liver tissue regeneration period. In marker-dependent subjects the susceptibility to chemotherapy of the remaining malignant tissue can be evaluated by changes in marker levels if these were still above normal values after partial hepatectomy. PMID- 2933661 TI - [Intermittent claudication of the buttock. Value of digital angiography]. PMID- 2933662 TI - [Granulomatous interstitial nephropathy and renal failure in sarcoidosis]. PMID- 2933663 TI - [Serum markers of hepatitis B among hospital personnel before vaccination]. PMID- 2933664 TI - [A reader's question or language problem: to benefit from an algorithm]. PMID- 2933665 TI - [Trisomy 21 and pericentric inversion of chromosome 9 in the parental karyotype]. PMID- 2933666 TI - [Colonoscopy detection of polyps in patients operated on for colorectal cancer. Prospective study]. AB - Subjects operated upon for colorectal carcinoma seem to constitute a population at high risk of a second colorectal malignancy and/or colonic adenoma (polyp). Ninety-four such patients were examined by colonoscopy. Their distribution by age and sex and the location of cancers in the colon were comparable to those reported in the literature. Colonoscopy was performed 12 +/- 6 months after surgery in 52 patients and was complete in 90% of them. Twenty-seven patients (52%) were found to have one or several polyps distributed throughout the colonic frame and varying in size from 2 to 75 mm (75% were less than 10 mm long). The larger the polyp, the more severe the dysplasia. Three malignant polyps were discovered; they were more than 10 mm in diameter. The colonoscopic examination was repeated annually over more than 3 years in 30 patients: at first repeat examination 54% had polyps which were still present in more than 30% at subsequent examinations. It is concluded that patients operated upon for colorectal carcinoma are at high risk of polyps and/or a second colorectal carcinoma and must therefore be followed-up by repeated colonoscopy. PMID- 2933667 TI - [Prostatic osteocondensing metastases and osteomalacia. Value of histomorphometric study. Preliminary results]. AB - A clinical, biochemical and histomorphometric study of non-decalcified bone with measurement of calcification rate was carried out in 10 patients with sclerotic bone metastases from prostatic carcinoma. The patients were under oestrogen therapy, and a change of treatment was being considered. The histomorphometric study showed that 3 patients had osteomalacia. These patients differed from the others in that the pain they experienced in bones was stronger, more diffuse and more often permanent. All three had fracture of the femoral neck. They had hypocalcaemia, hypophosphataemia, hypocalciuria and increased serum alkaline phosphatase, but only phosphataemia was significantly lower than in non osteomalacia patients. Osteomalacia was cured by vitamin D and calcium in one patient. Osteomalacia can only be reliably diagnosed in these patients by histomorphometry. This examination may be proposed to patients with sclerotic bone metastasis of prostatic origin, under hormonal therapy, presenting with diffuse skeletal pain or bone fragility without osteolysis, and with hypocalcaemia or hypophosphataemia. PMID- 2933668 TI - [Dyspnea with hypoxemia in a case of cirrhosis with portal hypertension]. AB - Following insertion of a Leveen's valve after surgical portocaval anastomosis, a male patient with alcoholic cirrhosis developed dyspnoea with hypoxaemia. An interstitial syndrome was present in the lower lobes. Other findings were: polycythaemia (Hb 20 g/100 ml), subnormal spirometric values, decrease in CO transfer capacity, normal pulmonary compliance, absence of intracardiac shunt and pulmonary arterial hypertension and absence of bronchial or alveolar lesions on a surgical lung biopsy. Blood gas measurements and radioisotope explorations led to the conclusion that the patient had an anatomical shunt predominant in the lower parts of the lungs, associated with a shunt effect and a transfer disorder. The anatomical shunt was due to pulmonary arteriovenous microfistulae, some of which were visualized by superselective angiography. Catheterization of the portocaval anastomosis eliminated any shunt between the portal system and the pulmonary veins. PMID- 2933669 TI - [Present and future value of monoclonal antibodies in nephrology]. AB - Many monoclonal antibodies directed against human T-lymphocytes have been produced in mice. Some of these, such as OKT 3, recognize all T-cells which can thus be counted in the blood; they have been used for the prevention of renal transplant rejection. Despite unexpected problems, such as antigenic modulation and anti-mouse sensitization, the first results obtained are promising. Other antibodies produced are directed against T-lymphocyte subsets, notably T-helpers (OKT4+) and T-suppressors or cytotoxic T-cells (OKT8+). Studies of the OKT4+/OKT8+ ratio have shown an imbalance in T-cell subsets in 2 types of glomerulonephritis: Berger's disease and membranous glomerulonephritis; they have also contributed to a better understanding of renal allograft rejection, where this ratio is often elevated. PMID- 2933670 TI - [Reversible pyloroduodenal exclusion. Method of temporary protection of the duodenal circuit]. AB - Reversible duodenal exclusion is a technique used to protect difficult duodenal sutures without the problems of permanent exclusion. It is effective throughout the healing period, then disappears when the suture material used for occlusion of the pylorus has been digested by the gastric fluid. Three cases are reported which confirm the usefulness of this technique. PMID- 2933671 TI - [Contribution of noninvasive technics of measuring cardiac output to the programming of pacemakers]. PMID- 2933672 TI - [Malignant melanoma after treatment with ultraviolet A rays and psoralen]. PMID- 2933673 TI - [Spontaneous peritonitis in systemic lupus erythematosus]. PMID- 2933674 TI - [Esophageal pH measurement: safeguard in surgery for gastroesophageal reflux without esophagitis]. PMID- 2933675 TI - [Inguinal lymph node plasmacytoma. Primary tumor or metastasis?]. PMID- 2933676 TI - [A new concept in the immunologic diagnosis of rubella]. PMID- 2933677 TI - [Superficial cervicocerebral angiomas. Should complementary tests be required?]. AB - A computer-assisted study of 772 patients with haemangiomas and vascular malformations was conducted during a 2-year period with special attention to complications and associated anomalies, such as laryngeal, meningeal or cerebral vascular malformations. We report here the data obtained from 397 of these patients totalling 401 superficial haemangiomas and vascular malformations of the head and neck. We classified the lesions into immature angiomas, growing and subsiding during childhood, and mature vascular malformations with a life-long development, themselves divided into arteriovenous, capillary and venous malformations. We found that each group had its own specific complications. Severe complications, notably vascular brain lesions, were eventually observed in patients with superficial arteriovenous malformations of the head. Extensive complementary investigations, including CT scans and arteriography, are therefore not justified in every case. Guidelines are offered to evaluate the risk according to the clinical diagnosis. PMID- 2933678 TI - [Lactic acidosis treated with thiamine. 3 cases]. AB - Of 3 alcoholic patients with severe lactic acidosis, one had shoshin beriberi; the second--a beer drinker--presented with convulsions associated with hyponatraemia and complicated by rhabdomyolysis and was not thiamine-deficient; the third patient had convulsions associated with Korsakoff's syndrome and was thiamine-deficient. In all three patients treatment with thiamine administered alone corrected the lactic acidosis within less than 4 hours. In patient 1, this result was obtained after symptomatic treatment of shock and lactic acidosis had failed and more than 24 hours before the haemodynamic disorders were corrected. In patient 2, who had no haemodynamic nor haematosis disorders, the lactic acidosis was corrected within 2 hours, i.e. more than 24 hours before neurological improvement developed. In patient 3, the lactic acidosis was also corrected within 2 hours. These results suggest that thiamine should figure among the treatments of lactic acidosis in alcoholic patients. Since thiamine alone is capable of correcting severe lactic acidosis, at least in some of these patients, it deserves to be tried in other types of lactic acidosis. PMID- 2933679 TI - [Chronic calcifying pancreatitis, pancreatic calculi. New data]. AB - There are two different forms of chronic pancreatitis: one is obstructive pancreatitis which results from a pre-existing obstacle (usually a tumour or a scar) and the other, much more frequent, is chronic calcifying pancreatitis which seems to begin with the formation of precipitates in acini and ducts, later transformed into stones and calcifications made up of calcium carbonate, and therefore is a pancreatic lithiasis. Since the pancreatic juice is supersaturated in calcium carbonate, the presence of an inhibitor of crystallization must be postulated. This has now been identified as a 13500 daltons molecular weight protein: the pancreatic stone protein secreted by the acinar cells. This protein is decreased in chronic calcifying pancreatitis irrespective of its origin (alcoholic, hereditary, hypercalcaemic, tropical, idiopathic), although its reduction is unrelated to any of these aetiological factors. Chronic alcohol consumption may encourage calcium stone formation possibly by disturbing the cholinergic regulation of pancreatic secretion, with decrease in citrate secretion (citrate is a chelator of calcium) and increase in enzyme secretion. The diagnostic and therapeutic implications of these findings are already obvious. PMID- 2933680 TI - [The so-called anterior tibio-peroneal trunk. Its influence on the mode of revascularization by femoropopliteal bypass]. AB - Femoro-popliteal bypass is difficult to perform when the posterior tibial artery originates at a high level in the lower limb. The problems arising from this anatomical variation, in which the tibio-peroneal trunk is, at least classically, anterior to the popliteal muscle, can be overcome by the technique described. PMID- 2933681 TI - [Esophageal exclusion by stapling]. PMID- 2933682 TI - [Possible responsibility of carboxyls in allergy and drug-induced hepatitis]. PMID- 2933683 TI - [Assay of glycosylated hemoglobin A1c in children. Determination of reference values]. PMID- 2933684 TI - [Sonography in the diagnosis and surveillance of acute rhabdomyolysis]. PMID- 2933685 TI - [Phenotype and functions of chronic lymphocyte proliferation associated with neutropenia in a female patient with rheumatoid arthritis]. PMID- 2933686 TI - [Isolated secretion of testosterone by adrenal cortex adenoma]. PMID- 2933687 TI - [2 unrecognized symptomatologic elements in impotence of venous origin]. PMID- 2933688 TI - [Bone marrow necrosis disclosing multiple myeloma of bone]. PMID- 2933689 TI - [Esophageal stenosis caused by neoplastic mediastinitis. Late complication of cancer of the breast]. PMID- 2933690 TI - [Digoxin assay in neonatology]. PMID- 2933691 TI - [Surgery aimed at a cure of pulmonary metastases]. PMID- 2933692 TI - [Autograft of bone marrow treated by immunotoxin T 101 for the treatment of T cell leukemia and lymphoma. Initial clinical cases]. AB - In order to consolidate a complete or partial remission, 4 patients with T-cell malignancy received cyclophosphamide 120 mg/kg plus total body irradiation, followed by reinfusion of cryopreserved autologous bone marrow purged in vitro by the immunotoxin T 101 (SR 41322) composed of the murine monoclonal T 101 antibody coupled with the A chain of ricin. The immunotoxin was applied in doses of 10(-9) and 10(-8) M for periods of 4 and 20 hours at 37 degrees C. The recovery of CFUc and BFUe progenitors was total following incubation with IT 101, but reduced after cryopreservation (1-15 to 80% for CFUc,-33 to 47% for BFUe), haematopoietic recovery occurred within normal delays, demonstrating that autologous bone marrow pretreated with the immunotoxin can be successfully transplanted. However, the slow increase in lymphocytes and the occurrence of lethal infection in 2 cases indicate that an in-depth study of immunological reconstitution after in vitro treatment of bone marrow with ITT 101 is necessary. PMID- 2933693 TI - [Peroperative monitoring of early auditory evoked potentials]. AB - Brainstem auditory evoked potentials (BAEP) were monitored during 37 neurosurgical operations (acoustic neurinomas with preoperative useful hearing, microvascular decompression of cranial nerves for hemispasm or trigeminal neuralgia, cerebellopontine angle tumors other than acoustic neurinomas, brainstem tumors and posterior circulation surgery). Intraoperative BAEPs were unchanged in 13 patients. Transient BAEP alterations (delay of I-V interval, transient obliteration of BAEP for as long as 8 minutes and 20 minutes) were seen in 13 other patients; irreversible BAEP alterations (loss of evoked response in 6 patients, delay of I-V interval) were seen in 11 patients. BAEP stability or alterations have been correlated with the ongoing surgical maneuver, the neurological outcome and the postoperative auditory function. BAEPs were found to be good predictors of post-operative auditory function but poorer predictors of neurological outcome. Some alterations are strictly associated with surgical retraction or with eighth nerve manipulation either immediately after the surgical maneuver or several minutes later. No detectable cause of BAEP changes was found in a few cases. The value of this monitoring is discussed. It may also help elucidate the mechanisms of hearing loss in acoustic neurinoma surgery. PMID- 2933694 TI - [Assisted respiration by stimulation of the diaphragmatic muscle. A case]. AB - Direct electrical stimulation of the diagram has resulted in physiological functioning in a quadriplegic patient. Mechanical ventilation could be partly withdrawn with 13-hour periods of "respiration". During the 2-month stay in hospital, 90 hours of respiration were obtained by stimulation. The patient died 8 weeks after the operation. PMID- 2933695 TI - [Allogenic interactions in immunopathology]. AB - Allogeneic interactions associated with experimental graft-versus-host reaction are sometimes responsible for the development of autoantibodies, immune complex lesions and malignant lymphocytic proliferation. Hypergammaglobulinaemia reflects the activation of B cells, and T cell-associated responses are deeply depressed. Some of these abnormalities are also found in chimera mice following injection of semi-allogeneic cells. The place of allogeneic interactions in human pathology has not yet been determined, but they might intervene in the pathogenesis of some autoimmune and lymphoproliferative diseases and in the acquired immune deficiency syndrome. PMID- 2933696 TI - [Aortic valve replacement in children by autograft of the pulmonary arterial wall]. AB - Since March 1984 we have been using a new biological valve for aortic valve replacement in children. The valve substitute is an autologous segment of cylinder taken from the pulmonary arterial trunk, leaving untouched the bifurcation and the pulmonary valve. The pulmonary artery wall segment is sutured without stand to the brim of the aortic annulus and upward beyond the aortic commissures to achieve adequate support from the aortic wall. The pulmonary artery itself is reconstructed by direct suture. This procedure has been successfully used in 3 patients aged 7, 10 and 13 years presenting with severe aortic regurgitation due to rheumatic heart disease. PMID- 2933697 TI - [Acute localized pneumopathies. Should macrolides always be prescribed initially?]. PMID- 2933698 TI - [Iodine poisoning caused by amiodarone]. PMID- 2933699 TI - [Failure of sodium nitroprusside prevention of arterial spasm during angiography by hyperselective catheterization in neuroradiology]. PMID- 2933700 TI - [Excretion of fats in urine after lithotripsy]. PMID- 2933702 TI - [Plasma fibronectin in acute leukemia]. PMID- 2933701 TI - [Doses of biogenetic human insulin for the treatment of diabetics with anti insulin antibodies]. PMID- 2933703 TI - [Performance of 8 methods for evaluating the free fraction of thyroxine in chronic renal insufficiency]. PMID- 2933704 TI - [Role of crossed allergy between a pneumallergen and an alimentary allergen in the recurrence of lipoid nephrosis]. PMID- 2933705 TI - [The apparent novelty of intra-arterial chemotherapy in the treatment of hepatic metastases]. PMID- 2933706 TI - [Panic attacks in adolescents]. AB - Anxiety has been the object of many therapeutic attempts, often in the absence of well-founded indications and often yielding inconclusive results. We obtained good results in two adolescents for whom we used a new classification system based upon the differential action of psychotropic drugs on anxiety. More specifically, this approach singled out the panic disorder by demonstrating that patients with this disorder react specifically to antidepressant drugs. More extensive studies are clearly needed to confirm that these results, well established for adult patients, also apply to an adolescent population. PMID- 2933707 TI - [Blood glucose and insulin secretion after meals rich in simple and complex carbohydrates, in non-insulin-dependent diabetics]. AB - In 10 well controlled non insulin-dependent diabetics, 25 g of complex sugars were replaced by the same amount of simple sugars in each of two isocaloric meals identical in their lipid, protein and carbohydrate contents. This had no detrimental effect on postprandial glycaemic and insulin responses. There were no statistically significant changes in areas under the curve and kinetics of glycaemic, insulin and peptide C responses after ingestion of limited amounts of simple sugars. It appears from these results that well controlled, non insulin dependent diabetic patients without marked postprandial fluctuations in glycaemia (as confirmed by self-performed capillary blood tests) can be authorized to take 25 to 40 g of simple sugars (preferably fructose) during meals. PMID- 2933708 TI - [Hurst-type acute leukoencephalitis with complete recovery in a child]. AB - A case of acute haemorrhagic leukoencephalitis in an 11-year old girl demonstrates the usefulness of computerized tomography which shows large, asymmetric hypodense areas in the white matter and diffuse oedema. The causative role of a Mycoplasma pneumoniae infection is suggested by positive serology and by a high level of cold anti-l agglutinins. Treatment with corticosteroids in massive doses combined with a tetracycline resulted in complete cure without sequelae. PMID- 2933709 TI - [Cardiovascular manifestations of sickle-cell anemia in children]. AB - Cardiovascular disorders are very frequent in children with homozygous sickle cell anaemia. They are due partly to the effects of chronic anaemia on the heart and vessels and partly to other factors, such as vaso-occlusive phenomena and desaturation of arterial oxygen, which alter the cardiac function. Because of reduced oxygen tension in arterial blood, the increase in resting cardiac output is more pronounced in sickle cell anaemia than in anaemias of other origins. Beside this "anaemic heart", myocardiopathies ascribed to multiple occlusions of small coronary vessels are well documented by pathological findings and by echocardiographic signs of left ventricular dysfunction. More rarely than adult children may develop chronic cor pulmonale due to large scale obstruction of the pulmonary vascular bed. PMID- 2933710 TI - [Gracilis muscle flaps for covering losses of perineal substance in cancer surgery]. AB - Myocutaneous or purely muscular flaps were used in 14 patients after extended surgical excision in the perineal region. When taking out the flap, its one pedicle and relatively weak blood supply must be taken into account. With this precaution, this technics can always be used for perineal resurfacing, particularly after total vulvectomy. In pelvic exenteration and amputation for anorectal cancer, it enables surgeons to fill the muscular gap, which seems to improve the post-operative course. It can also be used for vaginal, penile or sphincteric reconstruction. PMID- 2933711 TI - [Pharmacokinetics of mezlocillin in the pleural fluid]. PMID- 2933712 TI - [Mortality and morbidity of suicide attempted by firearms]. PMID- 2933713 TI - [Juvenile aponeurotic fibroma (Keasbey's tumor) may have an unfavorable course]. PMID- 2933714 TI - [Progressive idiopathic pleuropulmonary fibrosis]. PMID- 2933715 TI - [Association of Klinefelter's syndrome and cancer of the thyroid]. PMID- 2933716 TI - [Bilateral rupture of the Achilles tendon in Cushing's syndrome]. PMID- 2933717 TI - [Forecasting chemosensitivity of recurrent spinocellular cancer of the head and neck by xenograft beneath the renal capsule of syngeneic mice]. PMID- 2933718 TI - [Lyme disease: 2 new cases confirmed serologically]. PMID- 2933719 TI - [Colored indicators of hematuria]. PMID- 2933720 TI - [Primary pseudo-ovarian peritoneal carcinosis in an ovariectomized patient]. PMID- 2933721 TI - [Can pre-eclampsia be prevented?]. PMID- 2933722 TI - [Minimal etiological evaluation of Raynaud's phenomenon. 102 cases]. AB - The efficacy of a minimal aetiological investigation program was tested in a population with Raynaud's phenomenon. The program had been devised to fulfill the following criteria: non invasive, simple and relatively cheap methods capable of detecting systemic scleroderma at an early stage. These methods turned out to be physical examination, screening for antinuclear antibodies, capillaroscopy and radiography of the hands and chest. After investigations which, in addition to the minimal program, included exploration of the digestive and respiratory tracts, heart, kidneys, articulations and eyes, 102 consecutive cases of Raynaud's phenomenon were studied and divided into 3 groups: idiopathic (n = 15); secondary (n = 50, including 36 cases of collagen disease, 29 of which were systemic scleroderma), and suspected idiopathic or pre-collagen disease (37 cases of undetermined origin but not considered idiopathic in view of clinical and/or paraclinical abnormalities). In non idiopathic Raynaud's phenomenon, physical examination, capillaroscopy and screening for antinuclear antibodies gave abnormal results in 96.5% of the cases. This figure was raised to 98.8% when radiography of the hands and chest was added to these 3 examinations, but the difference was not significant. Since 96.5% of non idiopathic Raynaud's phenomena could be diagnosed by physical examination, capillaroscopy and screening for antinuclear antibodies, it is suggested that all patients presenting with the phenomenon should be subjected to these three simple examinations; negative results then dispense from supplementary investigations. PMID- 2933723 TI - [Treatment of acute colectasia not due to cryptogenic colitis. 4 cases]. AB - Four patients with acute colonic pseudo-obstruction were treated by colonoscopic aspiration. This treatment proved sufficient in 1 case due to Salmonella colitis and 1 case of parkinsonian dysautonomia. It has made it possible to diagnose a pyocholecyst masked by the colonic dilatation it had provoked, and facilitated its surgical treatment. A transient result was obtained in a case of otherwise asymptomatic choleperitoneum. Colonoscopy was relatively easy, perfectly well tolerated and always useful. It is therefore recommended for the treatment of acute colonic pseudo-obstruction except in cryptogenic colitis where its effectiveness and safety have not been demonstrated. PMID- 2933724 TI - [Role of chemotherapy in the treatment of gastric adenocarcinoma]. AB - In spite of the progress achieved in endoscopic detection and surgical techniques, the prognosis of gastric adenocarcinomas remains poor. To improve the results obtained, one of the most important lines of research is chemotherapy, but its place in the management of these tumours is still controverted. Apart from 5-fluorouracil, other active drugs recently developed (e.g. adriamycin, mitomycin, nitroso-ureas and cis-platinum) have been entered into new protocols and tested. The results at present available in patients with metastases are 40 to 50% complete or partial objective responses lasting for 4 to 16 months. They justify the use of these drugs, provided the patients' comfort is improved after the first two cycles. The place of adjuvant chemotherapy after complete surgical resection of gastric adenocarcinomas is still debated. Only 3 out of 13 randomized trials have demonstrated a longer survival in the treated group. Further controlled trials are required, using the most effective protocols, to determine their advantages and to find out which subgroups of patients are likely to benefit from chemotherapy. PMID- 2933725 TI - [The vascularized cross-leg flap]. AB - A better knowledge of the leg skin blood supply has recently revived interest in the cross-leg technique for skin grafts. It is now possible to delineate on each leg two flaps that contain arteries and veins. The internal saphenous flap, taken on the internal aspect of the leg is fed by the cutaneous branch of the greater anastomotic artery, satellite of the internal saphenous nerve, while the external saphenous flap, located on the postero-external aspect of the leg, is fed by 2 cutaneous branches of the popliteal artery or gemellar arteries. The length to width ratio of these flaps varies from 3 to 4, which is both safe and reliable and provides for supple handling of the pedicles and increased patient's comfort. PMID- 2933726 TI - [Biological proof of hyperandrogenism in hirsute women. Value of the assay of plasma delta 4-androstenedione]. PMID- 2933727 TI - [Cancers of the pancreas. A plea for excision]. PMID- 2933728 TI - [Duodenal diaphragm]. PMID- 2933729 TI - [The use of vancomycin in pregnant women]. PMID- 2933730 TI - [Passage of pefloxacine into the synovial fluid]. PMID- 2933731 TI - [Acute auriculo-ventricular block associated with Lyme disease. A case confirmed by serology]. PMID- 2933732 TI - [Pathogenesis of diabetic angiopathies]. AB - The paper is concerned with original data on decoding the involvement of disorders of the lipoprotein metabolism and circulating immune complexes in the mechanism of damage to the vascular wall in diabetes mellitus patients. In addition to raised LDL and VLDL levels, activation of lipid peroxidation in erythrocyte membranes as well as change of the spectrum of fatty acids were revealed. Two types of immune complexes were formed in diabetes mellitus patients: insulin--antiinsulin antibodies and insulin--VLDL. Under certain conditions each of these complexes can produce a vasodamaging effect. In the author's opinion, the existence of such complexes determines the specific nature of microangiopathies in diabetes mellitus patients. PMID- 2933734 TI - [Status and prospects of the problem of endemic goiter]. AB - The paper is concerned with the clinical problems of endemic goiter control. The stabilization of prevalence of thyroid hyperplasia has been shown as a result of underestimation of other than iodine deficiency giterogenic factors. Functional essence of the disease, a tendency to hypothyrosis, have been unraveled. Organizational problems and prospects of research in this area are considered. PMID- 2933733 TI - [Results of transplantation of pancreatic islet cell cultures to patients with diabetes mellitus]. AB - Altogether 110 intramuscular pancreatic islet cell (PIC) culture transplantations were performed in diabetes mellitus patients from April 1981 to May 1984 at the Research Institute of Transplantology and Artificial Organs, USSR Ministry of Health: 65 allotransplantations of human fetal PIC and 45 xenotransplantations fo swine fetal PIC. Immunosuppressive therapy was not employed. The paper is concerned with an analysis of a therapeutic effect of the IC cell cull culture transplantation on 30 patients who were followed-up for not less than 1 year after operation. A pronounced and long-term antidiabetic effect was observed in wost of the recepients subjected to the intramuscular human fetal PIC culture transplantation: demand in exogenous insulin decreased, a durable stabilization of a course of disease in patients with labile diabetes mellitus was observed, and in patients with such diabetic complications as polyneuropathy, retinopathy and glomerulosclerosis certain regress of these complications was observed. As to the results of the intramuscular swine fetal PIC culture xenotransplantation the authors note that xenogenic transplantation as compared with IC culture allotransplantation possesses a less noticeable offect on diabetes mellitus complications. PMID- 2933735 TI - [Dynamics of the detectability of tuberculosis and nonspecific lung diseases during mass fluorographic examinations of the rural population]. PMID- 2933736 TI - [Tuberculosis in Leningrad during World War II and the blockade]. PMID- 2933737 TI - [Organization of centralized dispensary examination of patients with extrapulmonary tuberculosis and their treatment in the RSFSR]. PMID- 2933738 TI - [Field examination of the population for the detection of tuberculosis and nonspecific diseases of the eyes]. PMID- 2933739 TI - [Characteristics of World War II invalids registered in tuberculosis dispensaries]. PMID- 2933740 TI - [Changes in cohorts of patients with tuberculosis in the Kazakh S.S.R]. PMID- 2933741 TI - [Anniversary of the V.I. Lenin Pediatric Tuberculosis Sanatorium]. PMID- 2933742 TI - Application of molecular biology to mental illness. Analysis of genomic DNA and brain mRNA. AB - Techniques in molecular biology and genetics have made it possible to systematically study gene effects in human disease. The number of gene clusters specifically encoding human brain structure and function is probably about 1,600 or half of all clusters. Evolutionary effects such as linkage disequilibrium and conservation of exons (DNA encoding structural proteins) as well as the fact that there are a tractable number of gene clusters involved, tend to make it quite likely that DNA pathology or DNA variation (polymorphism) predisposing to mental illness can be detected. Genes involved in mental illness can be detected either by studying DNA obtained from blood samples (genomic DNA) directly or by the analysis of mRNA and proteins from suitable cell or tissue preparations. The study of gene expression in the human brain is still in its infancy, nevertheless there are some hints that non-poly-adenylated mRNAs may be important in brain development and certain transcribed sequences may have a specific role in gene expression of the brain. The advantage of studying genomic DNA by the use of linkage and association analysis in multiply affected families is that it will, in the end, almost certainly yield a positive result for a disease with a substantial genetic input. Analysis of gene products from tissues such as brain could in theory detect specific disease genes but the approach will also identify genes secondarily affected by the disease process. Differentiation of genes that are primarily causing mental illness from those that are secondarily affected can be carried out by using such candidate genes as linkage markers in multiply affected families. PMID- 2933743 TI - Properties of memory T lymphocytes isolated from the mixed leukocyte reaction. AB - During the primary mixed leukocyte reaction, T lymphocytes of the lyt-2- helper subclass proliferate in response to transplantation antigens on allogeneic dendritic cells. We have isolated populations of antigen-specific proliferating lymphoblasts and recultured them in fresh medium. Within 2 days, the blasts become smaller in size, lose responsiveness to T-cell growth factor or interleukin 2, but retain vigorous reactivity to the original alloantigen. Two new biologic properties of these "memory" lymphocytes have been noted. First, they primarily respond to alloantigen on dendritic cells, whereas freshly sensitized lymphoblasts react to allogeneic dendritic cells, macrophages, and B lymphocytes. Second, the memory lymphocytes quickly aggregate with dendritic cells that are either syngeneic or allogeneic, but not with B cells. The aggregates that form with syngeneic dendritic cells disassemble within hours and do not release interleukin 2 or proliferate. The aggregates that form with allogeneic dendritic cells remain intact, release large amounts of interleukin 2 on the first day of culture, and synthesize DNA on the second day. Therefore, dendritic cells actively cluster memory lymphocytes by an antigen-independent mechanism, and this may underlie the heightened functional activity of each cell type. PMID- 2933744 TI - Natural effector T lymphocytes in normal mice. AB - The "natural" T-cell activity in normal unimmunized mice was studied. By double parameter fluorescence-activated cell sorter analysis, it was found that 5-10% of all splenic Lyt-2+ and L3T4+ lymphocytes are large, of which more than half are in mitotic cycle. In contrast with small resting cells of the same phenotype, activated (large) T cells isolated from normal mice are functional effector cells: L3T4+ large cells induce normal B lymphocytes into proliferation and antibody secretion, while large Lyt-2+ cells efficiently suppress B-lymphocyte responses. No effector cell cytolytic activity could be detected among naturally activated T cells. The significance of these findings for the internal activity in the normal immune system is discussed. PMID- 2933746 TI - Human beta-hexosaminidase alpha chain: coding sequence and homology with the beta chain. AB - We have isolated a cDNA clone, p beta H alpha-5, from an adult human liver library that contains the entire coding sequence of the alpha chain of beta hexosaminidase. The cDNA insert of p beta H alpha-5 is 1944 base pairs long and contains a 168-base-pair 5' untranslated region, a 186-base-pair 3' untranslated region, and an open reading frame of 1587 base pairs corresponding to 529 amino acids (Mr, 60,697). The first 17-22 amino acids satisfy the requirements of a signal sequence. A striking sequence homology with a published partial amino acid sequence for the beta chain [O'Dowd, B. F., Quan, F., Willard, H. F., Lamhonwah, A. M., Korneluk, R. G., Lowden, J. A., Gravel, R. A. & Mahuran, D. J. (1985) Proc. Natl. Acad. Sci. USA 82, 1184-1188] suggests that both chains may have evolved from a common ancestor. A shorter alpha-chain cDNA was found to hybridize to the long arm of chromosome 15, the known location for the alpha-chain gene. In addition, we isolated another alpha-chain cDNA clone, p beta H alpha-4, from a simian virus 40-transformed human fibroblast library that contained an extra 453 base-pair piece at its 3' end. A probe consisting of this additional sequence hybridized exclusively to a single mRNA species (2.6 kilobases) in mRNA preparations from cultured human fibroblasts. In contrast, p beta H alpha-5 hybridized to both a 2.1-kilobase major and a 2.6-kilobase minor mRNA species in these same mRNA preparations, indicating the presence of two distinct alpha-chain mRNA species differing at the 3' end. Fibroblasts from an Ashkenazi Jewish patient with classic Tay-Sachs disease were deficient in both species of mRNA, confirming their genetic relationship. PMID- 2933745 TI - Identification of a partial cDNA clone for the human receptor for complement fragments C3b/C4b. AB - Redundant oligonucleotides were synthesized based on amino acid sequences of tryptic peptides from the purified receptor for human complement fragments C3b/C4b (CR1). These probes were used to screen a size-selected human tonsilar cDNA library. A single positive clone was identified that hybridized to three oligonucleotide probes. The cDNA insert was 1.5 kilobases in length and contained sequences homologous to those of the oligonucleotide probes as well as nucleotide sequences corresponding to another independent CR1 tryptic peptide. Blot hybridization analysis using fragments of the cDNA insert as probes revealed two distinct species of the CR1 message of 9 and 11 kilobases in human tonsil mRNA. The two EcoRI fragments of the CR1 cDNA insert hybridized to each other, suggesting the presence of homologous sequences. When used as probes in Southern blot analysis of human DNA, each fragment identified similar but not identical patterns of multiple restriction fragments, indicating either a series of homologous domains in a single CR1 gene or the presence of multiple CR1 genes. Furthermore, an additional BamHI fragment was found to segregate with the expression of the S allotype of the CR1 protein in a family. Thus, the molecular weight difference in the polymorphic variants of the CR1 protein is based on differences in nucleotide sequences. PMID- 2933747 TI - Milrinone and thyroid hormone stimulate myocardial membrane Ca2+-ATPase activity and share structural homologies. AB - We have recently shown that thyroid hormone in physiological concentrations stimulates sarcolemma-enriched rabbit-myocardial-membrane Ca2+-ATPase in vitro. In this study, milrinone [2-methyl-5-cyano-(3,4'-bipyridin)-6(1H)-one], a cardiac inotropic agent, was thyromimetic in the same system. At clinically achievable concentrations (50-500 nM), milrinone significantly stimulated membrane Ca2+ ATPase in vitro. This action was antagonized by W-7 [N-(6-aminohexyl)-5-chloro-1 naphthalenesulfonamide], an agent that also blocks thyroid hormone action on the Ca2+-ATPase, at concentrations as low as 5 microM. Progressive additions of milrinone to membranes incubated with a fixed concentration of thyroxine (0.10 nM) or triiodothyronine resulted in a progressive obliteration of the thyroid hormone effect on Ca2+-ATPase. Amrinone [5-amino-(3,4'-bipyridin)-6(1H)-one], the parent bipyridine of milrinone, had no effect on myocardial Ca2+-ATPase activity. X-ray crystallographic analysis of milrinone and amrinone revealed structural homologies between the phenolic ring of thyroxine and the substituted ring of milrinone, whereas amrinone did not share these homologies. The mechanism(s) of the inotropic actions of thyroxine and of milrinone is not clearly understood, but these observations implicate Ca2+-ATPase, a calcium pump-associated enzyme, as one mediator of the effects on the heart of these two compounds. PMID- 2933748 TI - Characterization of the enzymatic lesion in inherited phosphofructokinase deficiency in the dog: an animal analogue of human glycogen storage disease type VII. AB - Mammalian phosphofructokinase (PFK; ATP:D-fructose-6-phosphate 1 phosphotransferase, EC 2.7.1.11) exists in multimolecular forms, which result from random tetramerization of three distinct subunits, M (muscle-type), L (liver type), and P (platelet-type), each under a separate genetic control. Human muscle and liver contain homotetramers M4 and L4, respectively, whereas erythrocytes contain a mixture of M4, M3L, M2L2, ML3, and L4 isozymes. Homozygous deficiency of the M subunit in man results in glycogen storage disease (GSD) type VII, which is characterized by exertional muscle weakness and compensated hemolysis; the residual erythrocyte PFK consists of isolated L4 isozyme. Recently, PFK deficiency associated with isolated hemolytic anemia has been identified among English springer spaniel dogs. We investigated the genetic control of the dog PFK system and the nature of the enzymatic defect in two PFK-deficient animals, using chromatographic and immunological techniques. Our studies indicate the existence of a trilocus isozyme system for the dog, as is the case with other mammals. Muscle PFK consists of M4 isozyme, whereas the predominant species of liver and platelet consists, respectively, of the L4 and P4 isozyme; erythrocyte PFK consists of a three- or four-membered set composed of M and P subunits. PFK deficiency in the dogs was found to result from a total and universal lack of the M subunit, as is the case in man. However, the probands consistently exhibited L4 isozyme in their muscle; P4, L4, and hybrids thereof in their erythrocytes; and an increase in the L-containing isozymes in their platelets, indicating a generalized anomalous presence of the L subunit. The apparent absence of muscle disease in these animals is most likely accounted for by both the well-known high oxidative potential of the canine muscle in general and the presence of liver PFK in the M-deficient muscle in particular. In contrast, presence of hemolysis despite residual P4 and hybrids of P and L in the erythrocytes may be inferred to result in severe glycolytic handicap under existing intraerythrocytic conditions. PMID- 2933749 TI - Class II major histocompatibility complex molecules regulate the development of the T4+T8- inducer phenotype of cultured human thymocytes. AB - We demonstrate that a variety of Ia+ cells has the ability to promote the development of human T4+T8- thymocytes in vitro. Prolonged thymocyte culture in the absence of Ia+ accessory cells results in a predominantly T8+T4- cell population. The generation of T4+ cells in the presence of irradiated Ia+ cells could be suppressed up to 70% by a monoclonal antibody directed against a nonpolymorphic epitope on HLA-DR. Using two-color fluorescence sorting techniques, we were able to identify the activated T4+T8+ thymocyte as the cell that interacts with Ia and gives rise to the T4+T8- cell subset. These results directly and specifically implicate class II major histocompatibility complex molecules in the differentiative pathway of the human thymocyte. PMID- 2933750 TI - The role of endogenous opioid peptides in the effects of constant illumination on reproductive function in the rat. AB - The present experiments assessed the involvement of endogenous opioids in the inhibition of FSH and LH release, ovulation and continuous sexual receptivity following exposure to constant illumination. In the first experiment, exposure to constant illumination resulted in persistent vaginal oestrus in all rats. The injection of naloxone resulted in marked elevations in serum FSH and LH, induced ovulation and increased the frequency of lordosis behaviour. It was concluded that endogenous opioid(s) participate in these effects. In Experiment 2, levels of beta-endorphin were found to be elevated in anterior pituitary and neurointermediate lobe tissue extracts from rats exposed to constant illumination, compared to levels in pro-oestrus rats. Naloxone injection into those rats exposed to constant illumination significantly increased hypothalamic levels of beta-endorphin compared to saline injected controls. This suggests that the blockade of opiate receptors increases beta-endorphin production, uptake and/or decreases its release from the hypothalamus. These results, and the known inhibitory action of beta-endorphin on LH release suggest that it may be this opioid, perhaps in conjunction with pineal products, which is responsible for the observed anti-reproductive effects of constant illumination. PMID- 2933751 TI - Evidence of norepinephrine-mediated suppression of para-chlorophenylalanine induced muricidal behavior. AB - Rats were made aggressive (muricide behavior) by p-chlorophenylalanine (p-CPA) treatment. The aggressive behavior was inhibited by the electrical stimulation of the locus coeruleus (LC) or by the administration of yohimbine (20 mg/kg i.p.). Both types of inhibition were blocked by the administration of low doses of clonidine (0.15 mg/kg i.p.). These results suggest the involvement of the adrenergic system in modulating muricidal behavior induced by p-CPA. PMID- 2933752 TI - Preference for high carbohydrate over various high fat diets by diabetic rats. AB - Streptozotocin-diabetic male rats were hyperphagic relative to nondiabetic controls when offered only high carbohydrate (CHO) laboratory chow. Diabetics and controls ate about the same amount of high fat diets made from 67% w/w chow and 33% either coconut oil (saturated) or safflower oil (unsaturated). However, when offered a simultaneous choice of high fat diets and chow, nondiabetics and low dose (35 mg/kg) streptozotocin-diabetics showed a preference for the high fat diet: in contrast the high dose (65 mg/kg) streptozotocin diabetics developed a preference for chow. When pairs of isocaloric synthetic diets were offered, diabetics again preferred low fat/high CHO to high fat/low CHO diets, but the actual intake of fat was not constant across different diet pairs. Nondiabetics also selected away from the high fat diets in these synthetic diet pairs, even when saccharin was added to the high fat diet in an attempt to equate its sweetness with that of the paired low fat-high CHO diet. Plasma ketone levels of diabetics during obligatory high fat diet consumption were negatively correlated with their subsequent preference for the fat diet over simultaneously-offered chow. These data show that strong dietary preferences do not develop for fat in diabetics and suggest that high fat diets do not have net beneficial postingestional effects in these rats. PMID- 2933753 TI - Autoimmunization against beta-endorphin increases food intakes and body weights of obese rats. AB - Opioid peptides in the brain are postulated to mediate the hunger component of the control of food intake and regulation of body weight and concentrations are increased in the pituitaries of genetically obese rodents. However, systemic increases in opioids have been associated with satiety. Thus a chronic decrease in systemic concentrations of the opioid beta-endorphin induced by autoimmunization was predicted to increase food intake and body weight. Zucker obese (n = 20, 568 +/- 13 g) and lean (n = 20, 299 +/- 16 g) rats were autoimmunized against bovine serum albumin (BSA) or BSA conjugated to beta endorphin (BSA-BE). Eight weeks after immunization serum from BSA-BE rats bound at least 7 times the circulating concentration of beta-endorphin. Food intakes were greater in BSA-BE obese (31.7 vs. 30.4 g/day, p less than 0.001) and lean rats (21.4 vs. 21.0 g/day, p less than 0.007) during weeks 5-8 and only obese rats, weeks 9-12 (31.8 vs. 30.3 g/day, p less than 0.009). Body weight gains were greater for BSA-BE than BSA obese rats during weeks 1-4 (1.34 vs. 0.92 g/day, p less than 0.05) and 9-12 (0.95 vs. 0.43 g/day, p less than 0.01). At 8 weeks the plasma concentrations of "free" beta-endorphin were decreased 78% (34 vs. 154 pmol/l, p less than 0.001) and "total" ("free" plus antibody-bound) beta endorphin were increased (427 vs. 101 pmol/l, p less than 0.001). These results suggest that systemic concentrations of beta-endorphin may play an important role in the control of food intake and regulation of energy balance. PMID- 2933754 TI - Thyroxine-induced cardiomegaly in rats of different age. AB - In the present study the effect of thyroxine treatment on the development of cardiomegaly was compared in young (10-day-old) and adult (12-week-old) rats. L thyroxine was administered subcutaneously in a dose of 1 mg per kg b.w. for 5 days. In young thyroxine-treated rats the heart weight increased by 79% in comparison with the control rats. The number of blood capillaries and muscle fibres per mm2 remained unchanged. The concentration of hydroxyproline was even lower than in control animals. The number of 3H-thymidine-labelled muscle cell nuclei was significantly higher both in the left and right ventricles of thyroxine treated rats. The density of capillaries and muscle fibres was significantly lower in adult rats than in the group of young animals. In adult thyroxine-treated animals the heart weight was higher by 36%, the number of capillaries and muscle fibres as well as the concentration of hydroxyproline was unchanged. Thyroxine induced significant increase in the number of DNA synthesizing nuclei of muscle cells in the left ventricle while the change in the right ventricular myocardium was not statistically significant. The present data indicate that a hyperplastic response of cardiac muscle cells to thyroxine occurs in both ventricles of young rats and also in the left ventricle of adult animals. PMID- 2933756 TI - Proceedings of the Czechoslovak Physiological Society. February 6-8, 1985. Abstracts. PMID- 2933755 TI - Effect of glucose, fructose, sorbitol and amino acid solutions employed in clinical medicine on the development of liver regeneration after partial hepatectomy. AB - The authors studied the effect of glucose (G), fructose (F), sorbitol (So), 4% Nutramin S Spofa (NuS) and Nutramin C Spofa (NuC) on development of liver regeneration. NuS is used clinically to improve a negative nitrogen balance, while the amino acid composition of NuC has a beneficial effect on the ornithine cycle and thus helps to normalize the NH3 level in patients with liver failure. Glucose seems to be the best substance for an optimal onset of liver regeneration. Its onset in rats given NuC was slower than in animals given NuS, but 48 h after partial hepatectomy there was no difference between NuC and NuS as regards the total DNA content and 96 h after the operation there was no difference as regards either the number of mitoses or the number of liver cells. In addition to reducing the plasma ammonia level, therefore, NuC also has a favourable effect on the development on liver regeneration. PMID- 2933757 TI - Double-pedicle transverse rectus abdominis myocutaneous flap for unilateral breast and chest-wall reconstruction. AB - Fifteen patients underwent unilateral breast and chest-wall reconstruction by a double-pedicle transverse rectus abdominis myocutaneous flap technique. Criteria for using both pedicles include (1) exceptionally large soft-tissue requirements, (2) prior abdominal operations compromising the vasculature to portions of the anterior abdominal wall, and (3) certain higher-risk patients with suspected microvascular pathology. Double pedicles allowed the transfer of the skin island as one unit or as two independent hemiellipses of tissue. Follow-up time ranges from 4 to 17 months. Complications included partial tissue loss in two patients, one abdominal flap seroma, and one patient with a hernia. PMID- 2933758 TI - Neuroendocrine and psychopathological measures in anorexia nervosa: resemblances to primary affective disorders. AB - Clinical and biochemical data suggest a link between anorexia nervosa (AN) and primary affective disorders (PAD). In 14 female patients, aged 15-40 years, with 7-month to 11-year histories of AN, we studied circadian cortisol periodicity, response to the dexamethasone suppression test (DST), and plasma levels of beta endorphin and beta-lipotropin before and after desimipramine therapy. Possible correlations were sought among neuroendocrine impairments, weight loss, and depressive symptomatology. Impaired circadian cortisol periodicity, blunted DST response, and increased beta-endorphin plasma levels, observed in a subgroup of patients, could not be related to weight loss, either before or after therapy. Instead, a trend toward a relationship between neuroendocrine impairments and depressive symptoms was observed before and after treatment. PMID- 2933759 TI - Perturbed angular correlation spectroscopy and its application to metal sites in proteins: possibilities and limitations. PMID- 2933760 TI - [5-fluorodeoxyuridine induces radioresistant synthesis of DNA and sensitizes HeLa cells to gamma radiation]. AB - It was shown that preincubation of HeLa cells with 5-fluorodeoxyuridine (10(-6) M) induced DNA synthesis resistant to gamma-radiation (6 Gy). At the same time, the death rate of exposed cells increased and nucleoid relaxation decreased. The role of DNA synthesis inhibitors in the reproductive death of exposed cells is discussed. PMID- 2933761 TI - [Mutagenic effect of the cytostatic drug thaliblastine on rat bone marrow cells when administered alone and in combination with radiation]. AB - The cytogenetic analysis was performed in the bone marrow cells of Wistar rats treated with a therapeutic dose of thaliblastine (250 mg/kg) and exposed to gamma rays (2 Gy). Thaliblastine alone induced chromosome aberrations and polyploid cells. The latter were the result of the stathmokinetic effect of the drug. In contrast to gamma-radiation of 2 Gy thaliblastine elicited a minor mutagenic effect. The cytogenetic effect of the combined treatment is greater than the sum of the two agents delivered separately, the maximum effect of radiation and thaliblastine being exhibited on the 8th and the 12th hour, respectively. The difference between the sum of aberrations after separate treatments and the yield of aberrations after the combined treatment is due to chromatid fragments. PMID- 2933762 TI - Percutaneous transluminal coronary angioplasty. AB - Percutaneous transluminal coronary angioplasty (PTCA) has revolutionized the treatment of patients with coronary disease. As many as 25 per cent of those requiring myocardial revascularization can now undergo PTCA instead of bypass surgery. This article reviews PTCA techniques, clinical results, case selection, complications, recent advances in equipment design, restenosis rate, use in acute myocardial infarction, and PTCA of coronary bypass grafts. PMID- 2933764 TI - Interaction of ethanol with drugs and vitamin therapy. PMID- 2933763 TI - Balloon embolectomy catheter used percutaneously. AB - Percutaneous arterial embolectomy was performed following percutaneous transluminal angioplasty in three patients using Fogarty balloon embolectomy catheters. This technique is effective for the treatment of arterial embolism resulting from angioplasty in selected situations. PMID- 2933765 TI - Legal case briefs for nurses. NC: is suicide attempt compensable? DC: patient raped: lack of nursing supervision. PMID- 2933767 TI - [The prevention of local and general causes of dento-maxillary anomalies in early childhood]. PMID- 2933766 TI - [Relation between causative factors and the location of mandibular fractures]. PMID- 2933768 TI - [The collage method in orthodontic resolution of dental impactions]. PMID- 2933769 TI - [Conditional situations in the surgical-orthodontic treatment of various dental impactions]. PMID- 2933770 TI - [Pit and fissure sealing--between wishful thinking and reality]. PMID- 2933772 TI - [Clinical results of collagen treatment in cases of accidental exposure of the pulp chamber]. PMID- 2933771 TI - [Generalized allergic dermatitis following xyline anesthesia]. PMID- 2933774 TI - [The double acid etched bridge]. PMID- 2933773 TI - [Aspects in the use of radiologic examination in prosthetic therapy (II-a): The correctness of clinical preparations in cases of the use of micro-prostheses with intra-radicular bonding]. PMID- 2933775 TI - [Epidemiological studies on the incidence of HBs antigen carriers and of hepatitis with positive HBs antigens in a dental health unit]. PMID- 2933776 TI - [Radiological changes in the diabetic periodontal disease]. PMID- 2933777 TI - [Determination of protease activity in the contents of periodontal pockets in chronic marginal periodontitis]. PMID- 2933779 TI - [Bruxism, para-function and self-destruction of the dento-maxillary apparatus, a distinct clinical entity. I]. PMID- 2933778 TI - [Protease activity and anti-protease activity in the saliva in chronic marginal periodontitis]. PMID- 2933780 TI - [Cytologic aspects of the oral mucosa in patients wearing Romacryl removable dentures]. PMID- 2933782 TI - [Kinetic sialography, a radio-cinematographic method for studying the salivary glands]. PMID- 2933781 TI - [Restoration of the loss of the upper 1st premolar in relation to the demands of periodontal prevention]. PMID- 2933783 TI - [Prevention of dental caries in pre-school children]. PMID- 2933784 TI - [Tooth extraction in the treatment of dento-maxillary anomalies]. PMID- 2933785 TI - [Trans-dental implantation to preserve an abutment tooth for removable dentures]. PMID- 2933786 TI - [Jessner's lymphocytic infiltration. Characterization of the cellular lineage with monoclonal antibodies]. PMID- 2933787 TI - Changes of plasma beta-endorphin like immunoreactivity induced by aging. PMID- 2933788 TI - Changing attitudes of disabled females through assertiveness training. PMID- 2933790 TI - Cognitive and behavioral dysfunction in multiply disabled children: an introduction. PMID- 2933791 TI - [Respiratory muscle fatigue]. PMID- 2933789 TI - Normalization: a concept of analysis. PMID- 2933792 TI - [Psychological characteristics of patients with chronic backache]. PMID- 2933793 TI - [Acute renal insufficiency and accelerated arterial hypertension of renovascular origin: treatment by endoluminal angioplasty. Apropos of 2 cases]. AB - In 2 patients with malignant hypertension and acute renal failure due to renal artery stenosis in a solitary functioning kidney, percutaneous transluminal angioplasty was used to dilate the stenotic renal artery. In both cases, hypertension resolved and renal function significantly improved. Follow-up angiographies revealed the continued patency of the dilated vascular segments. PMID- 2933794 TI - [Explicit behavior in a dental clinic of autistic children and a proposal for screening tests for cooperation during dental treatment]. PMID- 2933795 TI - [Toothbrushing in physically handicapped children (I)]. PMID- 2933796 TI - [An odontological study of Down's syndrome. 1: Eruption and crown dimension of the mesio-distal diameter of the deciduous teeth]. PMID- 2933797 TI - Clinical evaluation of a newly introduced noninvasive cardiac flow detector (CardioFlo). AB - Clinical evaluation on a newly-introduced cardiac flow detector (CardioFlo) was made on 6 patients. The correlation between the values obtained from the Swan Ganz catheter (thermodilution) and the present method was studied. A good correlation (r = 0.94) was demonstrated, which indicates clinical validity of this new method, especially when time is extremely limited as in emergency cases. PMID- 2933798 TI - [The nurse in Delta House 7 or the extent of the notion of nursing care]. PMID- 2933799 TI - [Nursing care during the dilatation of pulmonary valve stenosis]. PMID- 2933801 TI - [Myocardial hypertrophy and coronary circulation in aortic valvulopathies]. PMID- 2933800 TI - Atrioventricular conduction time in rheumatoid arthritis. AB - The atrioventricular conduction time (P-R interval) was determined in 189 women and 90 men with rheumatoid arthritis (RA). Only three women and one man were found to have pathological prolongation of the P-R interval. However, a significant prolongation of the P-R interval, within normal range, was seen in women with RA compared with healthy controls. Apart from the relation to radiographically enlarged heart, prolonged P-R interval showed no association with other signs of RA and had no prognostic implications in the follow-up period (mean 5.4 years). Current chloroquine therapy delayed the atrioventricular conduction while corticosteroids accelerated it. PMID- 2933802 TI - Interaction between complement component C4b-binding protein and the vitamin K dependent protein S. A link between blood coagulation and the complement system. PMID- 2933803 TI - Natural killer cell activity of human fetal liver cells after allogeneic stimulation. AB - Cells isolated from the liver of human fetuses were confronted with mitomycin C treated adult allogeneic cells. After this mixed leukocyte culture (MLC)-type reaction, the cytotoxic activity of fetal cells was tested against K562 cell line in a 4-h 51Cr release assay. Three of the seven fetuses tested (8 to 11 weeks of gestational age) expressed marginal cytotoxic activity before cultivation. Cells from one 8-week-old and one 9-week-old fetus were slightly more cytotoxic when cultured in the presence of allogeneic cells than when cultured in the medium only. Production of gamma interferon (IFN-gamma) was not detected in these cultures. Cells of one 18-week-old fetus expressed strong cytotoxic activity against K562 cells after MLC. Thymocytes from the same fetus were not cytotoxic, either before or after MLC against K562 cells. The results indicate that the 'prethymic' human liver contains cytotoxic cells able to spontaneously kill natural killer (NK)-sensitive target cells. Generation of strong NK-like cytotoxicity from noncytotoxic precursor cells was observed only after the thymus becomes lymphoid, suggesting that thymus-processed cells may regulate the generation of NK-like cytotoxic activity. The results suggest a different ontogeny of spontaneous and MLC-induced NK-like cells in the human fetus. PMID- 2933804 TI - Percutaneous transluminal renal artery dilatation for fibromuscular dysplasia with special reference to the acute effects on the renin-angiotensin-aldosterone system and blood pressure. AB - Twelve hypertensive patients (mean age 46.6 years, range 37-55 years) with fibromuscular dysplasia of the renal artery were treated with percutaneous transluminal renal angioplasty (PTRA) and the effects on the renin-angiotensin aldosterone system and blood pressure were studied in the acute phase. The technical result of PTRA measured by angiography and reduction of PRA and aldosterone excretion was satisfactory in 11 patients. In spite of this only three patients were cured of their hypertension and two patients were improved at six months follow-up. During PTRA an immediate rise in plasma renin activity was noted in patients without beta-receptor blockade but not in patients treated with beta-receptor blocking agents suggesting a beta-receptor mediated release. This peak in renin release was not accompanied by any rise in systemic blood pressure. The blood pressure response in the acute phase did not show any regular pattern. We conclude that PTRA can serve as a model for studying effects of 'clamping' and 'declamping' of the renal artery in man. PMID- 2933805 TI - [Immune defect following thymoma. Case description and review]. AB - The clinical and immunologic findings in a 57-year-old woman with hypogammaglobulinemia are described. The immunodeficiency occurred 11 years after surgical removal of an invasive lymphocytic thymoma. The typical findings of hypogammaglobulinemia as a thymoma-associated clinical syndrome are absence of peripheral blood B-lymphocytes and deficiency of plasma cells in bone marrow. However, in our patient peripheral blood B-lymphocytes and plasma cells in bone marrow were within normal limits, while the total number of peripheral blood mononuclear cells was subnormal. This subnormality was found to be a diminution of peripheral blood T-helper cells. Our patient was anergic to a battery of skin test antigens and her lymphocytes showed a decreased in vitro response to mitogen stimulation. In particular, the response to phytohemagglutinin (PHA) was low, but could be improved by the addition of interleukin-2 to the culture medium. Cocultures between patient B-cells and normal T-cells revealed normal function of patient B-cells. However, cocultures between patient T-cells and normal B-cells showed a significant depression of mitogen-induced immunoglobulin synthesis. These results are suggestive of T-helper cell dysfunction. Consequently, in our case the hypogammaglobulinemia was assumed to be secondary to deficient T-helper cell function. PMID- 2933806 TI - [Elimination of immune complexes: role of complement]. AB - For many years it has been considered that complement does not modify the immune elimination of antigen-antibody complexes. However, recent studies suggest that complement contributes to the normal processing of immune complexes: (1) complement activation modifies the structure of the immune complex lattice and produces soluble complexes, (2) erythrocytes bind complement reacted complexes and deliver them to the fixed macrophage system. The clinical association between inherited complement deficiency and immune complex mediated diseases also suggests a role for complement in the physiological elimination of complexes. PMID- 2933807 TI - Down syndrome--Alzheimer's linked. PMID- 2933808 TI - Biosynthesis and secretion of proatrial natriuretic factor by cultured rat cardiocytes. AB - Rat atrial natriuretic factor (ANF) is translated as a 152-amino acid precursor preproANF. PreproANF is converted to the 126-amino acid proANF, the storage form of ANF in the atria. ANF isolated from the blood is approximately 25 amino acids long. It is demonstrated here that rat cardiocytes in culture store and secrete proANF. Incubation of proANF with serum produced a smaller ANF peptide. PreproANF seems to be processed to proANF in the atria, and proANF appears to be released into the blood, where it is converted by a protease to a smaller peptide. PMID- 2933809 TI - Colocalization of band 3 with ankyrin and spectrin at the basal membrane of intercalated cells in the rat kidney. AB - An immunoreactive form of the anion channel protein of erythrocytes, band 3, has been identified in the rat kidney. It is found in the intercalated cells of the distal tubule and collecting ducts. Immunostaining specific for band 3 is confined to the basolateral plasma membrane of these cells, where this protein probably mediates the transport of bicarbonate across the tubular wall. Double immunolabeling studies demonstrate that band 3 is colocalized with immunoreactive forms of ankyrin and spectrin along the basolateral plasma membrane. The polarized distribution of band 3 may be the result of the association of its cytoplasmic domain with ankyrin, which in turn links band 3 to spectrin and the cytoskeleton. These observations help to explain how the collecting ducts of the kidney can direct the transport of bicarbonate ions, thus maintaining the acid base balance. PMID- 2933811 TI - The immunopathology of ankylosing spondylitis--a review. PMID- 2933810 TI - The 3' splice site of pre-messenger RNA is recognized by a small nuclear ribonucleoprotein. AB - A component present in splicing extracts selectively binds the 3' splice site of a precursor messenger RNA (pre-mRNA) transcript of a human beta-globin gene. Since this component can be immunoprecipitated by either autoantibodies of the Sm class or antibodies specifically directed against trimethylguanosine, it is a small nuclear ribonucleoprotein (snRNP). Its interaction with the 3' splice site occurs rapidly even at 0 degrees C, does not require adenosine triphosphate, and is altered by certain mutations in the 3' splice site region. Binding is surprisingly insensitive to treatment of the extract with micrococcal nuclease. The U5 particle is the only abundant Sm snRNP with a capped 5' end that is equally resistant to micrococcal nuclease. This suggests that, in addition to the U1 and U2 snRNP's, U5 snRNP's participate in pre-mRNA splicing. PMID- 2933812 TI - Radiological and scintigraphic findings in patients with a clinical history of chronic inflammatory back pain. AB - The prevalence of radiological abnormalities of the sacroiliac joints, the manubriosternal joint, and the lumbar spine were assessed, and quantitative sacroiliac scintigraphy was performed in 151 patients with a history of chronic inflammatory back pain and in 31 controls with non-inflammatory back pain. Sacroiliitis was found in 124 patients (82%), manubriosternal lesions in 84 patients (56%), and lesions of the lumbar spine in 58 patients (38%). In 19 patients (13%), manubriosternal lesions provided the sole radiological abnormality and in five patients (3%) no radiological abnormality could be demonstrated at any of these sites. Quantitative sacroiliac scintigraphy showed increased values in 69 of 137 patients examined (50%), but also in 10 out of 12 control patients with disc degeneration (83%) and is, therefore, nonspecific for inflammatory lesions. Radiological examination of the manubriosternal joint is recommended in patients with inflammatory back pain without radiographic evidence of sacroiliitis. PMID- 2933813 TI - Coping with a handicapped child: differences between mothers and fathers. AB - This paper considers coping styles of mothers and fathers of handicapped children. Cautioning against stereotyping, the authors find that mothers and fathers differ in how they appraise and cope with the stress of rearing a developmentally disabled child. The need for systematic investigation of gender related coping styles in families with handicapped children is discussed. PMID- 2933814 TI - Chronic low back pain: results of treatment at the Pain Therapy Center. AB - We evaluated the outcome of 100 consecutive patients with chronic benign low back pain admitted for comprehensive interdisciplinary rehabilitation at the Pain Therapy Center. The average patient had been disabled for nearly two years and had had two unsuccessful operations for pain relief. Seventy-two percent of the patients treated had open claims against their workmen's compensation carriers. Significant improvements were demonstrated in physical strength, stamina, endurance and overall level of physical activity, drug reduction, subjective pain intensity, and return to employment. PMID- 2933815 TI - Laparoscopic salpingectomy for ectopic pregnancy. AB - In selective cases operative laparoscopic salpingectomy is an alternative to laparotomy in the surgical treatment of ectopic pregnancy. The obvious advantages of this procedure are decreased morbidity and surgical pain, lower cost, shorter hospitalization and convalescence, and less disability, as well as a cosmetic surgical scar. Because the procedure is so cost-effective, and since the tools are familiar to most gynecologists, we hope it will gain wider utilization. Laparoscopic salpingectomy is not a difficult procedure when the basic principles of surgery are followed. Depending on the fertility desires of the patient and the condition of the opposite tube, this procedure may be preferable to laparotomy. If a complication such as bleeding does occur and fails to respond to cauterization, laparotomy can be done as usual for an ectopic pregnancy. PMID- 2933816 TI - Effect of high tension and relaxing incisions on wound healing in rats. AB - We developed four experimental models of rats and created abdominal wall wounds with various amounts of tension. We made the wounds under normal and high tension, both with and without relaxing incisions, and measured the bursting strengths and the rate of vascularization of the wounds. The results indicate that high closing tension impairs both of these parameters of wound healing and that relaxing incisions help in returning healing in high tension wounds toward normal. PMID- 2933819 TI - [Effectiveness of using thermographic examination of the upper respiratory tract]. PMID- 2933817 TI - [Prevention of childhood trauma]. PMID- 2933818 TI - [Socio-hygienic characteristics of pregnant women and parturients in a large industrial city and characteristics of the pathology of pregnancy and labor]. PMID- 2933820 TI - [Experience conducting a working model on the subject of the "dispensarization of the population in a district polyclinic"]. PMID- 2933821 TI - [Deontological aspects of the professional practice of students]. PMID- 2933822 TI - [Activities of the S.M. Kirov Military Medical Academy in Samarkand during World War II]. PMID- 2933823 TI - [Social assistance and patronage of evacuation hospitals of the Chuvash ASSR during the war]. PMID- 2933824 TI - [Morphological and clinico-laboratory parallels in podagra-associated nephropathy]. PMID- 2933825 TI - [Infectious antigenemia and circulating immune complexes in chronic brucellosis]. PMID- 2933826 TI - [Possibilities of the method of diagrams of logical structures in the management of training in a medical institute]. PMID- 2933827 TI - The radiographic evaluation of the symptomatic postoperative lumbar spine patient. AB - The diagnostic evaluation of patients with previous lumbar surgery presents a problem clinically and radiographically. The authors evaluated radiographically 75 patients with previous lumbar surgery who had persistent lumbar symptomatology. From their series, they found that a combination of two modalities (1) plain radiographs of the lumbar spine and (2) CT with intrathecal metrizamide and/or intravenous contrast provided the most complete and useful diagnostic information. The findings are presented with an emphasis on the pathologic changes demonstrated on the CT scans of the lumbar spine of which the most persistent findings were granulation tissue at the surgical site, lumbosacral spondylosis, recurrent or residual herniated disc, and arachnoiditis. PMID- 2933828 TI - Degenerative spondylolisthesis. Its surgical management. AB - Little attention has been given to the amount of further slip and the success rate after decompression for degenerative spondylolisthesis. In this retrospective study, the answers to the following were sought: (1) Did decompression relieve symptoms; (2) Which decompressive technique was best; (3) Did further slip occur; (4) Did further slip make patients worse? Seventeen patients were available for an average 20-month follow-up. Six patients had a decompression laminectomy with facetectomies, and 11 had a decompression laminectomy with foraminotomies. None was fused. Patients rated their results as better or worse at follow-up. Nine were better, eight were worse. Five of six who had laminectomies with facetectomies were better. Only four of 11 who had laminectomies with foraminotomies were better. The average further slip was 3 mm. Further slip did not correlate with type of decompression, symptoms, and patients' subjective results. We recommended that a decompression laminectomy for degenerative spondylolisthesis include a facetectomy. Further study is necessary to evaluate the efficacy of a fusion in controlling chronic back pain in the postdecompressed patient with degenerative spondylolisthesis. PMID- 2933829 TI - [Decreased C3b receptors of erythrocytes in patients with rheumatoid arthritis- with special reference to the vasculitis syndrome]. PMID- 2933830 TI - [Bone marrow necrosis. Apropos of 2 cases]. PMID- 2933831 TI - Treatment of colorectal hepatic metastases. AB - Hepatic metastases of colorectal carcinoma are present at diagnosis in 20 per cent of patients and occur within two years in 80 per cent of those which will recur in the liver. Surgical resection of all hepatic disease can confer survival on 20 per cent of resectable patients, but there is no other curative therapy. No systemic drug treatment has been shown superior to 5-FU alone, and the benefit of hepatic artery chemotherapy with FUdR (in contrast with systemic treatment) remains unproved. External beam radiation therapy with 3,000 rads offers effective palliation with low morbidity. The combination of chemotherapy with radiation treatment or hyperthermia may prove beneficial, but such protocols represent research rather than established treatment. PMID- 2933832 TI - Use of the Hickman catheter for jejunal feedings in children. AB - A simple, safe method for creating a long term jejunal feeding route using the standard Hickman catheter is described herein. The positive results in pediatric patients suggest that this method would be suitable in selected adult instances. PMID- 2933835 TI - [Amyloidosis in pulmonary tuberculosis and chronic nonspecific lung diseases in Leningrad hospitals for adults (autopsy data)]. PMID- 2933833 TI - Operative management of the kinked carotid artery. AB - In instances in which coexistent significant carotid artery disease and internal carotid redundancy coexist, we have found that use of the resected autogenous internal carotid artery to be a convenient and satisfactory way of patching the frequently small distal internal carotid artery following resection of the redundant portion. There has been no morbidity associated with additional suture lines, and in follow-up care extending through 24 months, there have been no recurrent symptoms. PMID- 2933834 TI - A detailed program review of in vitro fertilization with a discussion and comparison of alternative approaches. PMID- 2933836 TI - [Effect of hemosorption on the dynamics of immunopathologic changes in the skin of patients with diseases accompanying the immune complex syndrome]. AB - In the majority of diseases with the immune complexes (IC) syndrome, elimination of IC from the body is markedly disturbed. The authors carried out a study with the aid of the direct immunofluorsecence technique. The use of hemosorption in the treatment of patients with grave patterns of systemic lupus erythematosus, rheumatoid arthritis, psoriasis, systemic vasculitis and similar illnesses in conjunction with conventional therapy (corticosteroids, cytostatics) leads to sequestration of the depositions of immune complexes from the skin. As early as after the first hemosorption one can observe the displacement of IC from the derma to the epidermis, advance of IC towards the stratum corneum. After the third session in hemosorption IC granules appear on the body surface, in the form of warty formulations which are removed afterwards together with skin scales. It is assumed that hemosorption recovers the secretory function of the skin, aimed at IC elimination. PMID- 2933837 TI - [Clinico-immunological and biochemical indicators in the evaluation of pathological process in patients with rheumatoid arthritis]. PMID- 2933838 TI - [Prevalence and various social aspects of osteoarthrosis deformans]. PMID- 2933839 TI - [Quantitative and functional characteristics of T-suppressors in patients with rheumatoid arthritis]. PMID- 2933840 TI - [Changes in the functional activity of neutrophils during hemosorption therapy of patients with systemic rheumatic and other diseases with immunologic disorders]. AB - Fourteen patients on hemosorption therapy were studied for variations in functional activity of neutrophils isolated from peripheral blood. These variations were evaluated from neutrophil chemiluminescence during adhesion reflecting the generation of active forms of oxygen. A correlation was established between the positive effect of therapy and neutrophil activation which was most demonstrable by day 7 after the treatment. PMID- 2933842 TI - Isotretinoin (Accutane) treatment of acne. PMID- 2933841 TI - [Combined use of impact doses of 6-methylprednisolone and cyclophosphamide in patients with systemic lupus erythematosus]. AB - The priming doses of 6-methylprednisolone (6-MP) and cyclophosphamide (pulse therapy) were used for the treatment of 23 patients with SLE associated with primary involvement of the kidneys and pronounced immunologic disorders. The effect of combined therapy was evaluated on the extrarenal manifestations of SLE, proteinuria, hematuria, glomerular filtration, creatinine, antibodies to native DNA (anti-nDNA), complement, cryoprecipitins, antinuclear factor, and circulating immune complexes (CIC). The treatment efficacy was evaluated on day 4 since the beginning of the treatment and on the patients' discharge from hospital. The data obtained point to a significant increase of glomerular filtration and complement level, a reduction in CIC and anti-nDNA and cryoprecipitins within the first day after discontinuation of the treatment. The diminution of proteinuria and improvement of the urinary sediment were seen in over 50% of the patients. Variation of the laboratory findings correlated well with the improvement of the disease clinical picture. The combination of the priming doses of 6-MP and cyclophosphamide holds promise in the treatment of patients with associated SLE and grave renal involvement, marked immunologic disorders and generalized autoimmune vasculitis. PMID- 2933843 TI - [Physician and social insurance]. PMID- 2933844 TI - [The prevention of occupational eczema]. PMID- 2933845 TI - Effects of tranexamic acid on the conversion of Glu-plasminogen I and II to its Lys-forms. AB - Glu-plasminogen (Glu-plg) was incubated with plasmin. It took more than 2 hr incubation for the conversion of Glu-plg to a modified form (Lys-plg) to take place. Especially the conversion of Glu-plg II to Lys-plg II by plasmin took place very slowly. On the other hand, the conversion of Glu-plg I to Lys-plg I took place faster than that of Glu-plg II. In the presence of 1 mM tranexamic acid, the conversion of both Glu-plg I and II to their Lys-forms by plasmin was accelerated and completed in 30 min incubation. Fifty percent increase in the rate of the conversion of Glu-plg I to Lys-plg I was observed in the presence of 0.18 mM tranexamic acid. For the conversion of Glu-plg II to Lys-plg II, larger concentration of tranexamic acid was needed. Another observation was that tranexamic acid protected the degradation of plasminogen by plasmin, indicating the involvement of the lysine binding sites (LBS) of plasmin in the proteolytic attack against plg. PMID- 2933846 TI - Inhibition of platelet function by ticlopidine in arteriosclerosis obliterans of the lower limbs. PMID- 2933847 TI - [Reoperations of recurrent ischias]. PMID- 2933848 TI - [Occupational eczema. Diagnosis and treatment]. PMID- 2933849 TI - [P-pills for women with acne/hirsutism]. PMID- 2933850 TI - A human helper-dependent influenza virus-specific cytotoxic T lymphocyte clone restricted by HLA-DR2. AB - A human influenza A virus-specific cytotoxic T lymphocyte (CTL) clone is described that is restricted by a class II HLA-antigen. Of a large panel of B lymphoblastoid cell lines (B-LCL) as target cells the clone lysed only infected cells sharing HLA-DR2 with the donor of the clone. In cold target inhibition studies only infected cells bearing HLA-DR2 could inhibit cytotoxicity. Infected PHA-blasts that express less DR-antigen than B-LCL cells were lysed to a much lesser extent though they could be infected equally well. Trypan blue staining and postlabelling of the target cells showed that the clone indeed killed the target cells. The clone did not proliferate in response to infected irradiated autologous LCL cells and had the OKT3+4+8-DR+ phenotype. The possible significance of class II restricted CTL is discussed. PMID- 2933851 TI - [Day care in the Joseph House]. PMID- 2933852 TI - Abolition by nicorandil of spontaneous action potentials of the small atrio ventricular node preparation of the dog. AB - Effects of carbachol and nicorandil on spontaneous action potentials were examined in the small atrio-ventricular (A-V) node preparation of the dog. Carbachol (3 X 10(-6) M) definitely hyperpolarized the membrane potential and abolished the spontaneous activity. Nicorandil (3 X 10(-4) M) also abolished the spontaneous activity but the membrane potential became quiescent at -65 mV, which was less negative than the maximum diastolic potential. From these results it appears that nicorandil may increase the potassium conductances but not hyperpolarize the membrane potential because the background potassium conductance is little developed in the nodal cells. PMID- 2933854 TI - Ultraviolet irradiation of platelet concentrate abrogates lymphocyte activation without affecting platelet function in vitro. AB - We studied the effect of ultraviolet (UV) radiation on platelet concentrates. Samples irradiated at 310 mm for 30 minutes at a dose of 1782 J per m2 showed no loss of platelet function in vitro as determined by adenosine diphosphate, collagen, or ristocetin-induced aggregation. Lymphocytes isolated from irradiated units were unable to act as responders or stimulators in a mixed-lymphocyte reaction. These data suggest that UV radiation of platelet concentrates may result in a cell suspension that is unable to evoke an immunological response. PMID- 2933853 TI - [Pedagogic, scientific and social activities of Prof. K. I. Tatiev]. PMID- 2933856 TI - Suppressor cell activity of cells infiltrating rat renal allografts prolonged by perioperative administration of extracted histocompatibility antigen and cyclosporine. AB - Suppressor T cells were identified in situ within renal allografts of hosts rendered unresponsive by perioperative administration of donor histocompatibility antigen, which was extracted from donor spleen cells with 3M KCl, combined with cyclosporine (Ag-CsA). Infiltrating cells harvested from Buffalo (BUF, RT1b) renal allografts ten days after transplantation into Wistar-Furth (WFu, RT1u) rats treated with a single i.v. injection of 5 mg 3M KCl-extracted donor antigen (Ag) combined with a three day course of CsA inhibited the mixed lymphocyte culture (MLC) reaction between normal responder WFu and irradiated BUF cells (79.3% suppression, P less than 0.001), but not third-party Brown-Norway (BN, RT1n) stimulator cells (-5.4% suppression, NS). The suppressor effect was not due to cytolysis: the infiltrating cells did not lyse 51Cr-labeled concanavalin A (Con-A) blastoid BUF cells, as did the infiltrating cells from nonimmunosuppressed recipient allografts undergoing rejection responses toward BUF (49% specific cytolysis, E/T = 25), but not third-party BN, target cells five days after transplantation. The suppressor cells were nonadherent to plastic dishes and sensitive to monoclonal antibodies (Mab) W3/13 HLK (pan-T cells: % suppressor -17.9) or cytotoxic/suppressor cells with Mab OX-8 (-5.0% suppression), but not W3/25 (helper; 48.6% suppression, P less than 0.025). Moreover, adoptive transfer of 10(6) infiltrating cells from Ag-CsA-treated recipient allografts into virgin WFu hosts prolonged primary BUF graft survival from 7.2 to 14.0 days (P less than 0.05), but not third-party BN grafts (treated MST = 11.9 +/- 3.9 days versus untreated MST = 11.0 +/- 2.9 days, NS). On the other hand, infiltrating cells from CsA-only-treated recipient allografts could not transfer this effect (MST = 7.7 +/- 0.5 days, P less than 0.01). Finally, retransplantation of the BUF allograft from the Ag-CsA treated rat to a syngeneic, virgin WFu host ten days after primary transplantation yielded prolonged survival with MST 11.4 +/- 2.3 versus control primary graft survival in untreated animals of 7.2 +/- 0.6 days (P less than 0.001). BUF allografts from treated WFu hosts retransplanted into third-party BN rats did not display prolonged graft survival (MST = 9.2 +/- 1.1 days) compared with primary BUF grafts in untreated BN recipients (MST = 9.2 +/- 2.0 days, NS). The presence of suppressor T cells both in the spleen and in situ in renal allografts following Ag-CsA treatment suggests that local mechanisms may augment systemic elements to control the generation of alloimmunity. PMID- 2933855 TI - Dietary nucleotides, a requirement for helper/inducer T lymphocytes. AB - Previous investigations have revealed that dietary nucleotide restriction delays the onset of primary murine cardiac allograft rejection and acute graft-versus host disease followed H-2-incompatible bone marrow transplantation, suppresses sensitization to intradermally injected antigens and suppresses in vivo and in vitro lymphocyte proliferation to alloantigen or lectin stimulation. To determine the mechanisms responsible for these phenomena, BALB/c mice were placed on chow (F), nucleotide free (NF) diet, or NF diet supplemented with 0.25% RNA (NFR), with 0.6% adenine (NFA), or with 0.06% uracil (NFU). Following four weeks of dietary equilibrium, splenic lymphocytes harvested from naive or immunostimulated mice in the various dietary groups were stained with monoclonal antibodies directed Lyt 1, Lyt 2, 3, or surface mouse immunoglobulin (IgG) surface markers. While naive animals demonstrated no differences in lymphocyte subpopulations between groups, following complete Freund's adjuvant (CFA) stimulation, splenic lymphocytes for NF mice demonstrated 27.3 +/- 1.7% Lyt 1+ cells compared with F (32.6 +/- .04%) and NFR mice (33.2 +/- 1.2%) (P less than 0.02). Restriction of dietary nucleotides affected not only phenotypes of T lymphocytes, but also T cell function. Following conconavalin A stimulation of irradiated splenic lymphocytes, IL-2 production was decreased in NF mice compared with the F control group (P less than 0.01). The RNA-repleted diet maintained normal IL-2 production, while addition of adenine or uracil alone did not. Finally, NF diets adversely affected host resistance to the opportunistic pathogen Candida albicans. Following inoculation with 0.25 X 10(6) organisms NF or NFA-fed hosts succumbed more rapidly than F, NFR, or NFU fed hosts (P less than 0.001). These data suggest that helper/inducer T lymphocytes require exogenous nucleotides to respond normally following immune stimulation. Uracil may be the critical substrate, based upon the studies of Candida resistance. By understanding the metabolic basis of NFD-induced immunosuppression, the role of dietary nucleotides in combatting infection and alloantigen rejection can be more clearly defined. PMID- 2933858 TI - [Hirsutism treated with cyproterone acetate and ethinyl estradiol. Evaluation of the clinical effect]. PMID- 2933859 TI - [Roaccutan (isotretinoin) in the oral treatment of acne and rosacea]. PMID- 2933860 TI - [Multihandicapped children and adolescents in a residential institution before and after decentralization]. PMID- 2933857 TI - [Hirsutism treated with cyproterone acetate and ethinyl estradiol. Influence on androgens in the serum and urine and on urinary cortisol]. PMID- 2933861 TI - [Laparoscopy in chronic pelvic pain. A retrospective study of 151 laparoscopies]. PMID- 2933862 TI - [The risks and benefits of laparoscopic sterilization]. PMID- 2933863 TI - [Laparoscopy in chronic pelvic pain]. PMID- 2933864 TI - [Laparoscopic pancreatoscopy]. PMID- 2933865 TI - [Echocardiographic study of regression in the enlarged heart muscle during effective and long-term antihypertensive treatment]. PMID- 2933866 TI - [Work of military physicians of the 31st Army in the White Russian Operation]. PMID- 2933867 TI - [In the battle for the health of servicemen]. PMID- 2933868 TI - [The nurses' council of a military hospital]. PMID- 2933869 TI - [With a feeling of high responsibility (Vladlen Mikhailovich Mashoshin)]. PMID- 2933870 TI - [Changes in the concentration of cortisol, aldosterone and insulin in the blood of children with bronchial asthma during health resort treatment in a low altitude locale]. PMID- 2933871 TI - [High-altitude speleotherapy of children with bronchial asthma]. PMID- 2933872 TI - [Natural air ionization in high altitude locales and subterranean caverns of Kirghizia]. PMID- 2933873 TI - [Treatment of patients with myopathies at a climato-bath-therapy health resort]. PMID- 2933874 TI - [Organization of oncological services in the non-black earth region of the RSFSR]. PMID- 2933875 TI - [The role of organization measures in the early detection of lung cancer during mass screening]. AB - The experience gained in fluorographic mass screenings for early detection of lung cancer in Rostov Region showed their effectiveness to depend on differential selection of population study groups on the basis of examination periods determined according to the data of local registries, formation of high risk groups on the basis of the suggested criteria, and further research in the rhythm of fluorographic screenings in different population groups. Practical aspects of mass screenings deserve more attention. The percentage of lung malignancies detected in the course of mass screenings increased as a result of taking certain effective organizational measures, thus making the case for further research into the problem. PMID- 2933877 TI - [Catamnesis of patients with a history of acute myocardial infarct]. PMID- 2933876 TI - [Simultaneous development of 2 post-radiation sarcomas of the abdominal wall]. PMID- 2933878 TI - [Clinical-dispensary finding of patients with primary biliary cirrhosis]. AB - Ten patients with primary biliary cirrhosis (PBC) were clinically followed under the conditions of follow-up care. The diagnosis of the patients was made vie biochemical immunologic, histological and instrumental investigations. The average term for follow up was 4 years and 5 months. All patients were actively checked up by summoning every 6 months. The average incidence of hospitalization at the clinic was 1 year and 5 months. Pruritus preceded all other symptoms--1 year and 11 months on the average. Jaundice was established 1 year and 7 months after the manifestation of pruritus and the dirty greyish pigmentation of the skin--1 year and 11 months after pruritus. Hepatomegaly was established 1 year and 7 months after pruritus. Increased alkaline phosphatase, blood bilirubin and cholesterol were observed in all patients and increase of IgM in 80 per cent, and antimitochondrial antibodies--in 70 per cent. Xanthelasma and xanthoma were found only in patients with high levels of cholesterol and total fats. The treatment with dihydrocortison induced stomach complaints (erosive gastritis), intersifying bone chanes in 20 per cent of the patients. X-ray and instrumental methods have a relative value in making the diagnosis of PBC. It could be concluded from the complex treatment that corticosteroids give complications and the treatment with cholestiramine--to attenuation of pruritus. The average survival after making the diagnosis is 6 years. PMID- 2933879 TI - [Bioenergy metabolism in larvae of Trichinella spiralis spiralis and Trichinella spiralis pseudospiralis]. PMID- 2933880 TI - [Percutaneous transluminal angioplasty in the region of the renal artery- indications, technic and results]. AB - The paper reports the results obtained by percutaneous transluminal angioplasty (PTA) in the treatment of renal artery stenosis in 25 patients with secondary hypertension and discusses indications and the technique used. The follow-up period ranged from 0.5 to 12 months. All interventions were performed with the Olbert catheter system. Following PTA a significant decrease in systolic, diastolic and mean arterial pressure was observed in nearly all patients. The response of the plasma renin activity (PRA) to orthostatic stimulation and pharmacological stimulation by furosemide was determined in a subset of 15 patients before and after PTA. A significant decrease in both basal and stimulated PRA values was observed subsequent to PTA. The decrease in PRA values after successful PTA did not, however, correlate with the extent of the blood pressure changes. PMID- 2933881 TI - [Results of emergency aortocoronary bypass surgery in patients with acute myocardial ischemia after percutaneous transluminal coronary angioplasty]. AB - From April 1980 to June 1985 7.3% (15) of 205 PTCA-treated patients required emergency operations. The spectrum of PTCA-induced ischemia included anginal pain alone (2/1, 13%) or transmural infarction (13/15, 87%) with hypotension (8/15), cardiac arrest (4/15), and severe cardiogenic shock (3/15, 20%). 14 patients underwent saphenous-vein-bypass-graft operation (ACBG) with a mean of 1.7 grafts performed per patient. The average time from onset of symptoms to completed revascularisation was 166.5 (110 to 290) minutes. Inspite of the use of IABP one hospital death (6.6%) occurred prior to the institution of ECC in a patient with previous ACBG surgery. No late death was observed during a mean follow up of 11.1 (1 to 33) months with 13/14 patients free of anginal symptoms. Retrospective assessment of postoperative serum enzyme levels of CPK and CK-MB showed evidence of myocardial infarctions in 7/14 (50%) patient. The incidence on ECG of Q-wave infarctions was 35,7% (5/14). With the exception of one patient, IABP was not used pre- or postoperatively. In patients with acute myocardial ischemia following PTCA-attempts immediate restoration of myocardial blood flow can stabilize left ventricular function and reduce the incidence and size of myocardial infarctions. The availability of emergency ACBG-surgery and facilities remain an important prerequisite of PTCA-programs due to the unpredictable natural course of PTCA-induced myocardial ischemia. PMID- 2933883 TI - Can a 1,2-oxygen shift of a nicotinamide N-oxide derivative occur in vivo? AB - Using the N-oxide derivative of niaprazine, a nicotinamide-based drug, as substrate, the possibility of a 1,2-oxygen shift from N to adjacent C occurring in vivo has been investigated. By comparison of the percentage of the 6-pyridone derivative formed after administration of 14C-niaprazine to rats with that obtained after giving 14C-niaprazine N-oxide, it has been shown that a 1,2-oxygen shift might contribute to the formation of 6-pyridone derivatives as metabolites of nicotinamide-related drugs in vivo. PMID- 2933882 TI - [Surgical treatment of the isolated form of interrupted aortic arch]. AB - We report on a 14-years old boy with isolated interruption of the aortic arch (type B). By the use of extracorporal circulation complete relief could be achieved by interposing a large Dacron tube. Follow up restudy demonstrated a normotensive patient without residual gradient of the systemic blood pressure. PMID- 2933884 TI - On the maximal chronological age of man. AB - With the aim of clarifying the question on the maximal life span of man 144 the long-lived persons of the Azerbeijan SSR aged 90 and over were studied. To determine chronological age different research method, documents confirming age (passports, registers in village Soviets, etc.) were used, wedding dated, date of birth of their children were studied, memories on remembering historic events, ect., were checked. As a result of the complex determination of age, it was established that in 24.3% of the cases the age of the long-lived persons had been exaggerated. The maximal chronological age of man has been established as being 121 years. This age has been reached in the Azerbaijan SSR by men and women alike. PMID- 2933885 TI - [Dose and time relations of the effects of various asthma sprays in diagnostic use--a contribution to practicality of the bronchospasmolysis test]. PMID- 2933886 TI - [Modification of selected parameters in the laboratory rat by the effect of pesticides and humic acid]. PMID- 2933887 TI - [Syndrome of the absent umbilical cord in ultrasound]. AB - A case is presented of complete aplasia of the umbilical cord with concomitant severe anomalies of the fetus at 19 week's gestation. The sonographic findings are demonstrated and the pathogenesis of this rare malformation is discussed. PMID- 2933888 TI - [Coronary perfusion in acute vascular occlusion within the scope of transluminal coronary angioplasty]. AB - The procedure of coronary perfusion during transluminal coronary angioplasty (TCA) is described. By using guide wires of a length of 300 cm it is possible to exchange a balloon catheter for a perfusion catheter in acute vascular occlusion. Arterial blood is withdrawn and correspondingly supplied distal to the occlusion to meet the myocardial need for sufficiently oxygenated blood. Ischemia resolves, resulting in the normalization of left ventricular function and resolution of subjective complaints. This procedure can maintain myocardial oxygen supply until emergency coronary bypass graft surgery or repeat angioplasty. It might help to reduce mortality secondary to transluminal coronary angioplasty. PMID- 2933889 TI - [Measures for age adequate adjustment of work conditions]. AB - Within the framework of a research project on behalf of the organization "Humanisierung des Arbeitslebens" (Humanization of Working Life) we investigated under which conditions (economic, technical, organizational, and social) the places of work of both older workers with a changed performance level and handicapped workers can be modified in such a way that these employees can remain at their jobs. The goal was to find a method of employment which was geared both to performance abilities and to productivity. We also investigated the problem of how to arrange transfer jobs which fulfill the demand for qualified and productive employment, when it is no longer possible for the employees to remain in the job they have held up to then - for example, when the manufacturing process does not allow the modification of a single work place. The goal of gearing work places to the needs of older employees often fails in reality for various reasons. Especially worth mentioning are: lack of comprehensibility with regard to technical-ergonomic work aids - although there is a wide range of these available; general strategy of the firms to dismiss older workers and workers with a changed performance level; qualification deficiencies of older workers; and technical problems: i.e. in shift-working firms, when the modified job is taken over in the 2nd or 3rd shift by a worker with no health limitations. In spite of all assertions to the contrary, it has become clear that jobs for the handicapped and workers with a changed performance level can be conceived, so to speak, "in stock" as early as in the planning stage. PMID- 2933890 TI - [Rational preoperative diagnosis of cerebrovascular insufficiency--Doppler sonography, transvenous DSA, arteriography and arterial DSA]. PMID- 2933891 TI - [Gold-induced dermatitis (contact dermatitis and toxiderma)]. PMID- 2933893 TI - [History of the control of infectious skin diseases and syphilis in Turkmenistan (1867-1916)]. PMID- 2933894 TI - [Experience in the treatment of acne with the retinoid-roacutan]. PMID- 2933892 TI - [Cercarial dermatitis (schistosomiasis)]. PMID- 2933895 TI - New ways in counselling on prenatally diagnosed congenital malformations. An experimental information project using Bildschirmtext/Videotex. AB - A bibliometric analysis of source items recently published in German-language gynaecology journals and one German-language journal covering a broader field of medicine yielded but one publication linked with prenatally diagnosed congenital malformations and their surgical treatment. Thus, journals usually assessed by the gynaecologist are in this respect at present not a useful source of information for the practitioner outside specialised centres. In order to explore the usefulness of Bildschirmtext (BTX, Videotex), a new electronic medium, as an alternative in counselling for congenital malformations and similar rare medical problems, an experimental database was constructed. Pages giving data on diagnostic pathways, incidence, prognosis, specialised treatment centres and suggested further reading on abdominal wall defects were compiled and are stored in a central computer of the German Federal Postal Services. Data are accessible via the regular telephone network and a specially equipped TV set. The method, although still experimental, is considered useful for offering medical intelligence to the medical professional outside specialised centres. PMID- 2933896 TI - [Experimental animal studies of the subchronic toxicity of sintered bio vitroceramic materials in rat subcutaneous tissue]. PMID- 2933897 TI - [Histocompatibility of Ag-Sn-Cu-Sb amalgam and Ag-Sn-Cu amalgam in the subcutaneous implantation test]. PMID- 2933898 TI - [Method for determining the pathogenic properties of oral microorganisms and their toxins for resistant cells]. PMID- 2933901 TI - [Results of surgical treatment only of oral cavity carcinomas in the past 10 years]. PMID- 2933900 TI - [Long-term experience with the bridging of mandibular defects using free autologous bone grafts]. PMID- 2933899 TI - [Materials science studies of crown and bridge materials. 1. The possibilities of improving wear resistance]. PMID- 2933902 TI - [Ectopic pregnancy in uterus bicornis with rudimentary accessory horn on the side of the rudiment]. AB - Report on a patient with ectopic pregnancy at the side of a rudimentary horn of a uterus bicornis. The difficulty of a preoperative diagnose of the malformation and the possibility of a normal development of a pregnancy in the presence of uterine malformations are discussed, the external migration of spermatozoa and the combination with a renal aplasia, too. PMID- 2933903 TI - Epizootiological studies on porcine atrophic rhinitis. VII. Study of the aetiology and the local immune response. PMID- 2933904 TI - [Salmonella infections in children's playgrounds in Leningrad]. PMID- 2933905 TI - [Allomonas--a new group of microorganisms of the Vibrionaceae family. Allomonas enterica in seawater and various hydrobiotas]. AB - Bacteriological investigations made in the Black Sea, the Sea of Azov and the Sea of Japan have revealed that Allomonas enterica are widely spread in sea water and hydrobionts. The prevalence of these microorganisms in biotopes with unfavorable sanitary characteristics and their high correlation with the main indicator microorganisms suggest their importance as indicators, and a high percentage of seafood contaminated with Allomonas necessitates their study as possible causative agents of toxinfections. PMID- 2933907 TI - [Use of files for forms no. 063y in planning preventive immunization]. AB - The use of color-coded files, form No. 063y (prophylatic immunization records), with special cards, having a double row of perforations at the top, and with colored riders for the indication of months in planning and coverage with immunization considerably facilitates work in planning prophylactic immunization. The files can be rather easily analyzed for the coverage of the population groups with immunization without reading each card. As the plan of immunization for the current year is realized, the riders are used for planning the immunizations for the following years. Thus, at the end of the current year the plan for the next year, indicating the monthly schedule, and the kinds of immunization, is ready. PMID- 2933906 TI - [Formation of drug resistance in Vibrio cholerae of non-O1 group inhabitating surface-water reservoirs]. AB - In the study of 255 V. cholerae strains unrelated to vibrio O group I (NAG vibrios), which were isolated from water bodies in the region of the Volga delta in 1977-1982, antibioticograms of 17 types were obtained and R factor was detected in 37.7% of the strains under study. The pronounced heterogeneity of NAG vibrio populations, evaluated in minimal inhibitory concentration (MIC) values with respect to different antibiotics, is specifically manifested by the presence of various dominating subpopulations of these microorganisms, depending on their sensitivity to some chemical drugs. Various representatives of the genus Vibrio were used as a model for demonstrating the ability of the microbial population to enhance its variability as regards MIC values with a seasonal rise in the number of microorganisms. PMID- 2933908 TI - [Demyelinating encephalomyelitis in child native to Uzbekistan]. AB - Demyelinizing encephalomyelitis is described in a 7-year-old Uzbek girl. The clinical picture and a wave-like course of the disease were similar to the corresponding findings observed in children with multiple sclerosis who live in the European part of the USSR although both the patient and her parents are indigenous inhabitants of Uzbekistan and have never travelled beyond the borders of the republic. PMID- 2933909 TI - [Effect of treatment with psychotropic preparations on suppressor T-lymphocytes in juvenile continuously-progressing schizophrenia]. AB - The paper deals with the effect of psychotropic drugs on blood levels of suppressive T-lymphocytes in patients with continuously progressive schizophrenia. The patients were examined three times: the first sample of blood was taken after a long psychotropic therapy, the second 3 weeks after the discontinuation of the therapy and the third one 3 weeks after the resumption of treatment. The lowest levels of suppressory T-lymphocytes (averaging 16.3%) were observed during the first examination. Following the discontinuation of therapy the content of T-suppresspors increased to 21.3% (P less than 0.001) failing, however, to reach the mean level characteristic of normal donors (25.7%). The amount of suppressory T-lymphocytes decreased again after treatment resumption. It is concluded that one of the factors contributing to changes in the immunological status in patients with juvenile continuously progressive schizophrenia may be a long-term use of psychotropic drugs. PMID- 2933910 TI - [Cardiac and hemodynamic disorders in the pathogenesis of the initial manifestations of cerebrovascular pathology]. AB - Initial manifestations of cerebrovascular pathology (CVP) in the presence of arterial hypertension (n-26) and atherosclerosis (n-428) were combined with various cardiovascular disorders ranging from cardialgia to coronary heart disease in 67.4% of the patients. Cardial disturbances were expressed as an atypical pain syndrome in 47% and as angina of effort and postinfarction cardiosclerosis in 23.2% of the patients. Electrocardiographic changes were elicited in 52.6-62% of the patients. Bicycle ergometry revealed a decrease in all parameters of tolerance to physical exercise. Disorders of the general and cerebral hemodynamics were more pronounced in atherosclerotic patients; at the first stages of cerebral pathology they predominantly presented the normokinetic type of the hemodynamics (40.6%) while its more marked forms were associated with the hypokinetic type of the circulation (52). The early diagnosis of cardial and hemodynamic disorders is necessary for the presention of acute disturbances of the cerebral circulation. PMID- 2933912 TI - Autologous mixed lymphocyte reaction in Graves' disease: relationship to clinical status. AB - The autologous mixed lymphocyte reaction (AMLR), i.e. the ability of T lymphocytes to proliferate when cultured with autologous non-T cell fractions, is an 'in vitro' phenomenon showing immunological memory and specificity, probably related to the cooperation ability of immunocompetent cells. We have evaluated AMLR in 27 patients with Graves' disease of varying clinical status (untreated and treated with antithyroid drugs, surgery or 131I). The results obtained show: Impaired AMLR in untreated patients (as in other autoimmune diseases). Significantly higher AMLR in cured patients, and that AMLR in cured patients varies with the treatment (higher after surgery or radioiodine than after medical treatment). These results are consistent with the hypothesis of a functional defect of T cells in Graves' disease, which improves when clinical remission is achieved. PMID- 2933911 TI - T-lymphocyte subpopulations in type I diabetes mellitus. A longitudinal study. AB - Monoclonal antibodies were used to characterize peripheral T-lymphocyte subpopulations in 23 patients with type I diabetes mellitus. Initial measurements were made at diagnosis and in 10 of the patients further studies were carried out at 1, 3 and 6 months. T-cell subsets were also measured in 16 patients with type II diabetes, in 16 patients with various autoimmune diseases and in 17 healthy control subjects. At diagnosis, the type I diabetic patients showed a significant decrease in the percentage of cytotoxic/suppressor cells. Both total T-cells and helper/inducer cells were normal. However, when the helper/inducer population was analyzed in the context of islet cell antibodies (ICAs), it was found that those patients possessing ICAs had significantly higher proportions of helper/inducer cells than those lacking them. A significant inverse correlation was seen between the proportions of total T-cells and NK/K cells. At 1 month, the proportions of cytotoxic/suppressor cells returned to normal, whilst the helper/inducer cells showed a transient depression. By 6 months, the only change seen was a significant increase in the percentage total t-cells. No relationship was found between T-cell subset perturbation and metabolic control, as assessed by measurement of hemoglobin A1 (HbA1). The type II diabetic patients showed a significant increase in the percentage of total T cells. The autoimmune patients also showed a significant increase in the proportions of total T-cells; this appeared to reflect an increase in the helper/inducer subset. In the autoimmune patients these findings occurred in conjunction with significant decreases in the absolute numbers of each T-cell subset. It is surmised that, in some cases of type I diabetes, alterations in immune homeostasis may permit autoimmune processes, which lead to cell damage at the onset of diabetes. PMID- 2933913 TI - Follicular rupture changes the endocrine profile of peritoneal fluid. AB - We determined the concentration of progesterone (P) and 17 beta-estradiol (E2) in peritoneal fluid 32 hours after endogenous luteinizing hormone surge (LH) or 34 hours after injection of human chorionic gonadotropin (hCG) in 4 groups of patients: group A: 5 natural cycles, unruptured follicles, mean concentrations of P (1.48 micrograms/l) and E2 (169 ng/l); group B: 28 stimulated cycles, unruptured follicles after an endogenous LH surge, mean concentrations of P (5.33 micrograms/l) and E2 (1 344 ng/l); group C: 13 stimulated cycles, ruptured follicles after endogenous LH surge, mean concentrations of P (446 micrograms/l) and E2 (59 500 ng/l); group D: 8 stimulated cycles, unruptured follicles after injection of hCG, mean concentrations of P (8.21 micrograms/l) and E2 (551 ng/l). The variations of the hormonal concentrations in peritoneal fluid are discussed. PMID- 2933914 TI - Prevalence of sexual dysfunctions in non-insulin dependent (type II) diabetic males. AB - Since previous papers about the frequency of sexual dysfunctions (SD) in diabetic males did not consider the genetical and clinical heterogeneity of diabetes mellitus, we studied the prevalence and the pathogenesis of SD in 77 non insulin dependent diabetics (NIDD). The diagnostic procedures consisted of physical and psychological examinations, compilation of a questionnaire, evaluation of autonomic and peripheral nervous systems, measurement of penile arterious flow, dosage of hormonal and metabolic parameters. SD were present in 52% of patients: 24% of them had organic impotence, 28% psychological sexual impairment. Age, duration of diabetes and metabolic control were superimposable in the patients with and without SD. Most patients with organic impotence had an alteration of parasympathetic nervous system; less frequently a reduced penile arterious flow was observed. The relief of such a high prevalence of SD in NIDD males suggests that future studies should consider the various groups of diabetics separately. PMID- 2933915 TI - Success of in vitro fertilization and embryo transfer in relation to the causes of infertility. AB - In 1984 163 patients were treated in our in vitro fertilization program, including 4 patients accepting embryos from the oocyte and embryo donation program. Twenty pregnancies were achieved with an average chance per transfer of 16,6%. The final success of IVF strongly depends on the cause of infertility. The best results were obtained for patients with tubal infertility, with a pregnancy rate of 15% per laparoscopy and 19% per transfer. There is a significant decrease in oocyte cleavage rate from tubal (61%) to male infertility (13%). Once the barrier of embryo formation is taken, there is no marked difference in the mean number of embryos transferred on the pregnancy rate after transfer, among the different patient groups. In patients with tubal infertility the pregnancy rate per cycle remains constant, resulting in a cumulative pregnancy rate of 40% after 3 cycles. PMID- 2933916 TI - [Metabolism of progesterone in fetal membranes. The effect of sex steroids and gonadotropin-releasing hormone on progesterone metabolism in fetal membranes]. PMID- 2933917 TI - The effects of dichloromethylene biphosphonate on osteoporotic femora of adult castrate male rats. AB - In a previous study we reported that castration of adult male rats resulted in femoral osteoporosis 4 months later. The present study tested the effects of dichloromethylene biphosphonate (Cl2MBP, formerly Cl2MDP), a bone resorption inhibitor, on the development of osteoporosis in femora of adult castrated male rats. One-year-old male Holtzman rats were assigned to three groups: sham operated controls; castrated-no treatment; castrated + Cl2MBP injections 3 times/week. The animals were sacrificed 4 months later. Femora from untreated castrated rats were osteoporotic, confirming our earlier study. Femora from Cl2MBP-treated castrates did not differ from those of controls and were significantly denser and more robust than those of untreated castrated rats. The results indicated that Cl2MBP treatment started immediately after castration prevented the development of femoral osteoporosis in adult castrated male rats. PMID- 2933918 TI - Further regression of seminal vesicles of castrated guinea pig by administration of cyproterone acetate. AB - It has been established that a low level of secretory activity persisted in seminal vesicles of guinea pigs long after castration and that this may be due to a higher extratesticular androgen level in this animal. A RIA study revealed that the normal serum testosterone concentration of the guinea pigs was comparable to that of the rats, but the basal serum testosterone level after castration was ten times higher than rats under a similar condition. It was also shown that cyproterone acetate did not significantly lower the basal serum testosterone concentration in the castrated guinea pigs. The higher basal serum testosterone level is believed to be responsible for the slow and incomplete regression of this gland in the guinea pigs. There was a significant reduction in wet weight of the seminal vesicles after the treatment of castrated guinea pigs with cyproterone acetate. Ultrastructural study showed that there were both qualitative and quantitative changes in the cytoplasmic organelles. The Golgi apparatus further reduced in size and in the number of associated vesicles and vacuoles. There was a marked decrease in the number and size of secretory granules and lysosomes and an increase in the degree of undulation of the basement membrane. Accumulation of lipid droplets and glycogen was commonly observed. All these morphological evidences showed that further regression of the castrated guinea pig seminal vesicles can be achieved by cyproterone acetate treatment. PMID- 2933919 TI - [Visceral manifestations of leprosy]. PMID- 2933921 TI - Fusion for low back pain and sciatica. PMID- 2933920 TI - Peripheral nerve axonal dwindling with concomitant myelin sheath hypertrophy in experimentally induced diabetes. AB - Axons of the peripheral nervous system (PNS) are reduced in caliber in response to the experimental diabetic state. The cause of this reduced axonal size is disputed. Various theories include (a) axonal dwindling, (b) inhibition of growth, and (c) shrinkage due to serum hyperosmolarity. This study was designed to directly address these conflicting theories and to provide additional information on the character of the peripheral neuropathy resulting from an experimentally induced diabetic state. Four weeks, 6 and 12 months after establishing a streptozotocin-induced diabetic condition in rats, a morphometric evaluation of randomly selected cross sections of myelinated nerve fibers in the common peroneal nerve was performed on diabetic and age and weight-matched control animals. A reduction in the cross-sectional area of axons with a concomitant increase in the width of myelin sheaths was detected following 6 months of exposure to the diabetic state. Axons in rats diabetic for 12 months showed smaller cross-sectional areas than those seen in rats diabetic for only 6 months; hence, a dwindling in axonal caliber had occurred during this period. These findings indicate the presence of an axonopathy, associated with a myelin sheath alteration in the common peroneal nerve of the chronically diabetic rat. PMID- 2933922 TI - Intercorporal lumbar spondylodesis. 312 patients followed for 2-20 years. AB - Intercorporal spondylodesis was performed for low back pain in 120 patients with spondylolisthesis and 192 patients with disc degeneration; the latter group had all had previous surgery. The operations were carried out with retroperitoneal access, in most cases using iliac grafts, and additional posterior screw fixation in a number of patients substantially shortened the postoperative immobilization time. Complications were one death from pulmonary embolism, one case of possible genital disturbance, four inconsequent infections and three vessel injuries. In each group less than 10% had an additional operation for early signs of non fusion. In cases without concomitant spinal problems, the overall fusion rate was 95-98 per cent. Clinically, the spondylolisthesis group was superior with 75 per cent without low back pain and 95 per cent without radicular pain postoperatively versus 55 per cent and 77 per cent for the disc degeneration group. PMID- 2933923 TI - Vasomotor changes in human skin elicited by high frequency low amplitude vibration. PMID- 2933925 TI - Renal transplant artery stenosis and percutaneous transluminal angioplasty. AB - Ten patients with renal transplant artery stenosis were treated with percutaneous transluminal angioplasty (PTA). All patients suffered from hypertension refractory to drug treatment. PTA was successful in five patients. Blood pressure improved significantly and the antihypertensive medication could be reduced or withdrawn. Acute angulation at the anastomosis prevented successful PTA in four patients. One inaccessible stenosis was corrected surgically. No significant complications arose. If a renal transplant artery stenosis is haemodynamically significant, PTA should be considered the method of first choice for correction. PMID- 2933924 TI - The current status of percutaneous coronary angioplasty. AB - The present status of percutaneous coronary angioplasty is presented, with a brief outline of current technique, the technical and clinical indications for the method, and the results being obtained. Coronary angioplasty is only applicable in a minority of patients currently undergoing coronary angiography for ischaemic heart disease, but even with its present technical limitations, the results being obtained and its obvious advantages in selected cases have assured its status as a significant advance in the treatment of coronary disease. PMID- 2933926 TI - Nephrotoxicity of ionic and non-ionic contrast media in aorto-femoral angiography. AB - Nineteen patients examined with aorto-femoral angiography were randomized into two contrast medium groups (meglumine metrizoate and iohexol). Urine activity of beta-hexosaminidase, a specific renal enzyme, was determined before and on three occasions after angiography. No change of beta-hexosaminidase activity was found after angiography with iohexol, while there was a significant increase after examination with meglumine metrizoate. This indicates that meglumine metrizoate even following injection into the abdominal aorta damages renal cells which could not be shown with iohexol as contrast medium. We therefore recommend that at least patients with impaired renal function should be examined with the non-ionic contrast medium iohexol to minimize the danger of further damage to the kidneys and a possible renal failure. PMID- 2933927 TI - Reticuloendothelial cell function in autoimmune hemolytic anemia (AIHA): studies on the mechanism of peripheral monocyte activation. AB - We examined the activity of peripheral blood monocytes in patients with autoimmune hemolytic anemia (AIHA) using an in vitro assay of monocyte-macrophage interaction with erythrocytes and an antibody-dependent cell-mediated cytotoxicity (ADCC) assay. The monocytes of AIHA patients in the hemolyzing period phagocytized autologous sensitized red cells and anti-D coated red cells more avidly than normal control monocytes. There was no significant relationship between phagocytic activity and ADCC activity. The activated monocytes phagocytized autologous sensitized red cells, but had no ADCC activity in a short time 51Cr release assay. Phagocytic activity of the patients' monocytes against autologous erythrocytes rapidly decreased after treatment with prednisolone even though the red cell sensitization with antibody remained almost the same as during the hemolyzing period. We postulated that the activation of monocytes in AIHA was due to the "arming" effect of anti-erythrocyte antibody, but we think that other mechanisms may also be involved in the activation of monocytes. PMID- 2933928 TI - Intracoronary streptokinase in acute myocardial infarction. A review. AB - The attempt to salvage myocardium threatened by ischemia during temporary or permanent occlusion of one or more of the nutrient arteries, is based on the observation that the major determinant of survival is the extent to which myocardium has been lost through infarction. Modern clinical cardiology has therefore looked at various approaches which might limit unnecessary loss of potentially viable myocardium. These are attempts to reduce the oxygen consumption through pharmacological means, attempts at restoring the blood supply and oxygen delivery at an early stage by manipulations on the coronary arteries and interventions aimed at "protecting" cardiac cells threatened by ischemia or reperfusion. Endpoints considered to be proof of improved left ventricular function will be wall motion and ejection fraction measurements as well as reduction in death rate and other serious cardiovascular complications. Although final proof from prospective randomized studies, one of which is carried out at this institution with intracoronary streptokinase in over 300 patients, will not be available at the time of this presentation, arguments will be provided which indicate that restoration of blood supply at an early stage, preferably supported by pharmacological therapy with beta-blockade and calcium antagonists, is to be preferred inasmuch as current data indicate improved function, and in certain subsets, improved life expectancy. PMID- 2933929 TI - Transluminal coronary angioplasty--state of the art 1984. AB - Since its introduction in 1977 by Gruntzig, percutaneous transluminal coronary angioplasty (PTCA) has been increasingly applied to the treatment of coronary artery disease manifested by symptomatic ischemia. Initially only recommended for proximal short stenoses of one major coronary artery, the indication for PTCA has gradually been enlarged. Today even distally situated coronary stenoses in more than one vessel can be dilated successfully by using a steerable system. In experienced hands, an immediate improvement can be achieved in about 90% of the patients. In the realm of cost and morbidity PTCA offers obvious advantages over bypass surgery. However, indications for PTCA are more restricted than those for bypass surgery, specially in multi-vessel disease where the application of PTCA is still controversial. Moreover, long-term results are less favourable after PTCA since 25-30% of the patients show a recurrence within 6 to 12 months. Although PTCA will not replace coronary bypass surgery, it is already established as an alternative and complementary method for coronary revascularization. PMID- 2933931 TI - [Periodontal disease in children]. PMID- 2933930 TI - Prevention of cerebral vasospasm with OKY-046 an imidazole derivative and a thromboxane synthetase inhibitor. A preliminary co-operative clinical study. AB - The prevention of cerebral vasospasm with OKY-046, an imidazole derivative and a thromboxane synthetase inhibitor, was studied co-operatively at ten neurosurgical services. Intravenous administrations of 2, 5 or 10 mu/kg/minute of OKY-046 were given continuously from the earliest possible day to the 14th SAH-day to 82 patients with ruptured cerebral aneurysm. Sixty-eight patients (83%) showed moderate to high high-density (SAH) in their initial CTs. Angiographic vasospasms were seen in 58 patients, representing 71% of all cases or 81% of the 72 cases for which angiograms were available: the vasospasms of 45 patients (55 or 63%) were moderate to severe. Symptomatic vasospasm occurred, however, only in 27 patients (33%): in 18 of those cases, moreover, the symptoms were mild or transient. The conditions of the patients at one month after the SAH were classified into 9 grades from 0 (normal) to 8 (deceased). Fifty-two patients (63%) were classified as 0 or 1, and 64 (78%) as better than 3 (possible daily life unaided). The administration of OKY-046 was proven to decrease TXB2 in the blood. This paper emphasizes the effectiveness of the drug for symptomatic vasospasm, and supports our previous contention that cerebral microthrombosis may play an important role in the pathogenesis of cerebral vasospasm. PMID- 2933932 TI - Lipoplasty of the torso in patients over fifty. AB - This article describes the author's experience in performing lipoplasty in patients over 50 years of age. Historically, emphasis was placed on selection of patients for this procedure who were under age 40 years. However, the author's experience with 20 patients over 50 indicates extremely high patient satisfaction. Subsequent skin excision was required in only 10% of the patients. The author concludes that many patients over 50 have good skin elasticity and represent satisfactory candidates for lipoplasty. Age alone should not exclude these patients. PMID- 2933933 TI - Method for determining arterial entry site for catheter. PMID- 2933934 TI - Radiologic manifestations of small-bowel toxicity due to floxuridine therapy. AB - Floxuridine (5-FUDR) is an antipyrimidine used in the treatment of metastatic colorectal carcinoma. Bowel toxicity, manifested predominantly by diarrhea and abdominal pain, is one of the main complications of 5-FUDR therapy. Six patients who had received 5-FUDR infusion either by hepatic arterial or systemic intravenous routes subsequently developed severe diarrhea and were evaluated by small-bowel series. Radiographic changes were largely confined to the ileum. In four of six patients, the entire ileum or its more distal part was markedly narrowed. In the other two patients, changes consisted of thickening or effacement of the mucosal folds in the distal ileum. The symptoms of all six patients resolved after discontinuation of 5-FUDR therapy. This was accompanied by improvement in the radiographic appearance of the ileum in three patients who underwent a subsequent small-bowel series. The finding of reversible ileal changes, particularly extensive or segmental narrowing, seems to be a characteristic radiographic feature of bowel toxicity due to infusional 5-FUDR delivered by either the intraarterial or the systemic route. PMID- 2933935 TI - [Immunoglobulin D--new insights into its structure and function]. AB - The IgD is unique with regard to its structure, differences between species, genetic organization and behaviour in the immune response. With the successful analysis of the structure a new picture of the function has been emerged. The function of the membrane-bound IgD as a trigger receptor of B cells is qualitatively different from the mIgM. The secreted form could act as an intercellular messenger in the network regulation of the immune response. The mechanisms of the induction and maintenance of the immunological memory and tolerance remain unclear. PMID- 2933936 TI - [Radioimmunological determination of neopterin in blood donors]. AB - In 518 sera from blood donors below 30 years of age Neopterin was determined by radioimmunoassay. 21 of these patients (= 4.05%) showed elevated serum levels for Neopterin. By clinical investigation of these cases viral infections of the upper airways were found. Furthermore after elimination of elevated values significant differences in normal Neopterin serum levels could be demonstrated for female and male blood donors (p less than 0.01). Because elevated Neopterin serum levels indicate immune responses to several antigens, determination of Neopterin from serum may be useful for detection of infectious blood samples. PMID- 2933937 TI - Local immunodeficiency of the intestinal mucosa--a contribution to etiopathogenesis of recurrent urticaria and diarrhoea. AB - The case of a 10 month-old girl with a history of recurrent urticaria and diarrhoea is presented. Immunological study was carried out and secretory component in sputum, duodenal juice and stool was not found, while IgA was detected. Peroral biopsy of intestinum was also carried out and histology revealed partial villous atrophy. Immunofluorescent staining showed only a few IgA and IgG producing cells scattered within the villous stroma, while the IgM producing cells were increased in number. Serum concentration of IgA, IgM and particularly IgG was increased. Both parents had measurable IgA in the serum, however, the secretory component was not detectable neither in mother nor in father. The deficiency of secretory component and deficiency of IgA producing cells in the jejunal villous stroma led to local immunodeficiency of the intestinal mucosa and that caused recurrent urticaria and diarrhoea in the girl presented. PMID- 2933938 TI - [Isolation of monocytes by adherence to gelatin-layered surfaces]. AB - The method for purification of monocytes using adherence to gelatin coated glass surfaces described by Chien et al. was optimized by drastic shortening the incubation time and modifying the culture media. After one adherence step we obtained monocytes with a purity of 73-78% and a recovery of 53%. Thiol-protein disulfide-oxidoreductase (TPO), a new enzyme marker of monocytes, was found to be also valid for monocytes obtained by adherence methods. Comparing the number of TPO-containing monocytes with other markers (alpha-naphthylacetate esterase, peroxidase, phagocytosis of latex particles, acridine orange fluorescence, antigens detected by the monoclonal BL-M/G antibody) almost identical values were found. PMID- 2933939 TI - Lectin-induced thermostable SE-rosette (TSER) formation by human peripheral blood lymphocytes. AB - Lectin-activated human peripheral blood lymphocytes were able to form thermostable rosettes with sheep red blood cells (SRBC). Capability to form thermostable rosettes (TSER) after lectin treatment was comparable in time kinetics and dose dependence to cell size distribution changes. Enhancement of TSER formation by human lymphocytes exposed to PHA and Con A, however, occurred before 3H-Thymidine incorporation could been registered. Lectin treatment of lymphocytes from 20 healthy donors for 48 hrs induced 49 +/- 4% (PHA), 33 +/- 5% (Con A), and 20 +/- 2% (PWM) thermostable rosette forming cells, whereas in unstimulated cultures were found 4 +/- 1%. Furthermore, thermostable rosette forming cells were enriched by gradient centrifugation and characterized as activated lymphocytes of T-origin by SE rosetting and binding studies with various monoclonal antibodies. It was shown that preparation of TSER forming cells after lectin activation makes it possible to enrich the fraction of lectin stimulated T lymphocytes. PMID- 2933940 TI - Age interference of lymphokine production by lung derived lymphocytes. AB - Young adult and aged guinea pigs, 1 and 3 years old respectively, were sensitized intranasally with Bacillus Calmette Guerin (BCG). Lung lavage cells were harvested at 2, 3, 6 and 7 weeks following sensitization and tested for migration inhibitory factor (MIF) production in Mackaness chambers with purified protein derivative (PPD). Oil induced normal pig macrophages were used as indicator cells. Aged guinea pigs, compared to young adult guinea pigs, showed significant delay and reduced levels of MIF production at 2 to 3 weeks. Delayed hypersensitivity skin reaction (DHS) to PPD was also less pronounced at 6 weeks. Senescent immune lung cells were inhibitory to migration of indicator cells in absence of PPD. PMID- 2933941 TI - Reduced atrial natriuretic factor after ligation of the left coronary artery in rats. AB - The diuretic-natriuretic responses of eight assay rats to extracts of atrial tissue obtained 3 months after left coronary ligation were less than the responses to extracts of tissue from sham-operated controls. The mean difference in diuresis (sham-operated response minus ligated response) was 370 (range 22 to 656) microliter/20 minutes (p less than 0.01) and in natriuresis 56 (range -92 to 222) microEq/20 minutes (p = 0.19). The differences in diuretic responses to these extracts was directly related to the severity of elevation of left ventricular end-diastolic pressure in these rats (r = -0.82, p = 0.01). These results in a model with varying degrees of left ventricular dysfunction suggest that myocardial damage is associated with a chronic decrease in atrial natriuretic factor. Reduced circulating atrial natriuretic factor therefore could contribute to the previously observed impaired ability of coronary ligated rats to excrete a saline load and to the sodium retention observed in clinical heart failure. Conclusive evidence will depend on the development of techniques to measure plasma levels of this hormone. PMID- 2933942 TI - Increased injury of hypertrophied myocardium with ischemic arrest: preservation with hypothermia and cardioplegia. AB - Many patients undergoing cardiac surgery have some degree of myocardial hypertrophy. To assess the response of hypertrophied myocardium to simulated cardiac surgery, left ventricular hypertrophy was induced in rats by aortic banding, and ventricular function was measured by means of the isolated, isovolumic heart perfusion technique. The hypertrophied hearts had a greater susceptibility to ischemic injury than nonhypertrophied control hearts, as manifested by a greater degree of diastolic contracture during the recovery period after 30 minutes of ischemic arrest at 37 degrees C. Hypothermia without cardioplegia during a 2-hour arrest did not completely preserve diastolic function in the hypertrophied hearts, but cardioplegia combined with hypothermia completely protected the hypertrophied hearts against 2 hours of ischemia. The results suggest a need for both hypothermic and cardioplegic preservation techniques in patients with myocardial hypertrophy who have cardiac surgical procedures requiring a significant period of myocardial ischemia. PMID- 2933943 TI - Applicability of laser to assist coronary balloon angioplasty. AB - Severe atherosclerotic obstructed coronary artery disease (CAD) may preclude passage of a balloon catheter for transluminal coronary angioplasty (TCA). Since lasers have been shown to effectively vaporize CAD plaque, the initial application of laser to effect a lumen large enough to accommodate the angioplasty catheter for further dilatation was explored. Eleven postmortem human CAD segments which did not permit passage of a 1.33 mm shaft diameter angioplasty catheter were studied. Argon laser radiation (14 to 90 J) transmitted via 400 micron core diameter quartz fiber onto the stenotic channel of 0.58 mm created a vaporized lumen of 1.77 mm (mean increase of 1.31 +/- 0.25 mm, p less than 0.001). The laser procedure allowed the balloon angioplasty catheter to be pushed into the stenosis. TCA was then performed (7 atm, 45 seconds) and expanded the channel to 2.12 mm (additional mean increase of 0.38 +/- 0.07 mm, p less than 0.001). In terms of percent luminal narrowing, laser radiation reduced obstruction from 80% to 45% (mean difference of -38.7 +/- 4.6%, p less than 0.001), and TCA caused a further decrease to 37% (mean difference of -9.3 +/- 1.9%, p less than 0.001). Thus, in tight atherosclerotic lesions, the laser may be useful in creating an initial opening enabling the placement of the balloon angioplasty catheter which, in turn, can further dilate the lased stenotic coronary lumen. PMID- 2933944 TI - Renal failure due to cholesterol emboli following PTCA. PMID- 2933945 TI - Sudden death and hypertrophic cardiomyopathy. PMID- 2933946 TI - Coronary angioplasty in myocardial infarction. PMID- 2933947 TI - Coronary artery occlusion seven weeks after angioplasty successfully managed with repeat emergency angioplasty. PMID- 2933948 TI - Doppler evaluation of left ventricular diastolic filling in children with systemic hypertension. AB - To assess left ventricular (LV) diastolic function in children with systemic hypertension, 11 patients with hypertension (mean blood pressure 99 mm Hg) and 7 normal patients (mean blood pressure 78 mm Hg) underwent M-mode echocardiography and pulsed Doppler examination of the LV inflow. From a digitized trace of the LV endocardium and a simultaneous phonocardiogram, echocardiographic diastolic time intervals, peak rate of increase in LV dimension (dD/dt), and dD/dt normalized for LV end-diastolic dimension (dD/dt/D) were measured. Doppler diastolic time intervals, peak velocities at rapid filling (E velocity) and atrial contraction (A velocity), and the ratio of E and A velocities were measured. The following areas under the Doppler curve and their percent of the total area were determined: first 33% of diastole (0.33 area), first 50% of diastole, triangle under the A velocity (A area), and the triangle under the E velocity (E area). The A velocity (patients with hypertension = 0.68 +/- 0.11 m/s, normal subjects = 0.49 +/- 0.08 m/s), the 0.33 area/total area (patients with hypertension = 0.49 +/- 0.09, normal subjects = 0.58 +/- 0.08), the A area (patients with hypertension = 0.17 +/- 0.05, normal subjects = 0.12 +/- 0.03), and the A area/total area (patients with hypertension = 0.30 +/- 0.11, normal subjects = 0.20 +/- 0.07) were significantly different between groups (p less than 0.05). M mode and Doppler time intervals, (dD/dt)/D, E velocity, and the remaining Doppler areas were not significantly different between groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2933949 TI - Hemodynamic effects of calcium entry-blocking agents in normal and hypertensive rats and man. AB - To be considered ideal for the treatment of hypertension, a class of drugs should produce a maintained reduction of arterial pressure primarily through a fall in total peripheral resistance that is at least uniformly distributed through the organ circulations of the target organs of hypertensive vascular disease. Such drugs should be useful as monotherapeutic agents, should not expand the extracellular fluid compartment, should not reflexively stimulate the heart and vessels, should reverse the structural changes in the target organs without compromising function and, of course, should be relatively free of adverse effects. As a heterogeneous class of agents, the calcium entry-blocking drugs fulfill most of these criteria, although preliminary studies suggest that their effects on organ vascular resistances and on structural cardiovascular changes are highly variable. Thus, further vigorous investigation of these new agents is highly recommended. PMID- 2933950 TI - Effects of calcium entry blockers on renin-angiotensin-aldosterone system, renal function and hemodynamics, salt and water excretion and body fluid composition. AB - The renal effects of the calcium entry-blocking drugs diltiazem, nifedipine, verapamil and nitrendipine are reviewed. Although nifedipine stimulates plasma renin activity on a short-term basis, none of the calcium entry blockers produces a clinically significant sustained effect on any of the components of the renin angiotensin-aldosterone system. Although all of the calcium entry blockers effectively lower blood pressure, none adversely affects renal function; glomerular filtration rate and effective renal plasma flow are maintained. Diltiazem may increase glomerular filtration rate via attenuation of the intrarenal effects of angiotensin II or norepinephrine. Although diltiazem and nifedipine increase salt and water excretion on a short-term basis, none of the calcium entry blockers produces a clinically significant sustained effect on salt and water excretion; serum electrolytes, urinary sodium and potassium excretion, body fluid composition and body weight are unchanged. Thus, calcium entry blockers can be expected to assume a prominent role in the treatment of hypertension because of their ability to lower blood pressure while preserving renal perfusion and function. PMID- 2933951 TI - Age, race, blood pressure and renin: predictors for antihypertensive treatment with calcium antagonists. AB - Age, race, pretreatment blood pressure and plasma renin activity have been related to the antihypertensive response to calcium antagonists in studies that included 215 patients with mild to moderate essential hypertension. Adverse effects necessitated withdrawal from therapy in about 10% of the patients. All calcium antagonists lowered blood pressure significantly and comparably without weight gain or reflex tachycardia. In a multiple linear regression analysis of 138 white patients, age, pretreatment blood pressure and renin activity were of independent and significant predictive value for the antihypertensive response. Stratification of patients into 3 age groups disclosed a greater effect in patients older than 60 years compared with those between 40 and 60 years and those below 40 years, respectively (p less than 0.01). In 16 middle-aged black patients, antihypertensive therapy with a calcium antagonist proved highly efficacious. Monotherapy with a calcium antagonist may become a first-line treatment for essential hypertension, particularly in older patients who have low renin activity and possibly in black patients as well. PMID- 2933952 TI - T-cell lymphoma mimicking granulocytic sarcoma. AB - A case of diffuse large cell lymphoma is described in which eosinophils and eosinophilic myelocytes were admixed with the neoplastic lymphoid cells. Because of the eosinophilic myelocytes, a diagnosis of granulocytic sarcoma was initially considered. No abnormalities of peripheral blood or bone marrow were found. Immunohistochemical studies of lymph node tissue demonstrated membrane antigens consistent with a lymphoma of helper T-cells. Small lymphoid cells with markedly irregular nuclei were present but rather inconspicuous among the larger lymphoid cells. Although a clinical remission was attained, the patient had a relapse with central nervous system involvement. PMID- 2933953 TI - Psoas abscess complicating Crohn's disease. AB - Psoas abscess classically was described as secondary to tubercular spondylitis but now more frequently is a complication of an intraabdominal process such as Crohn's disease. Less well recognized is that the fever, flexion contracture of the hip, and weight loss characterizing psoas abscess may be the first indications of Crohn's disease; in fact, gastrointestinal symptoms may be completely absent. Psoas abscess was the first sign of Crohn's disease in 11 of 46 reported patients. We present three additional patients; two were asymptomatic before psoas abscess formation. Only seven of 26 patients whose sole surgical procedure was drainage had subsequent resolution of the abscess. When drainage was combined with bowel resection, 14 of 18 patients (77.8%) were cured by the initial procedure. Thromboembolic complications occurred in four patients (8.3%). Effective therapy when psoas abscess complicates Crohn's disease, includes appropriate antibiotics, drainage, resection of fistulous intestine, and antithrombotic prophylaxis. PMID- 2933954 TI - Dermatitis from repeated trauma to the skin. AB - A moderate degree of friction is unavoidable in everyday contact between man's skin and his environment. However, excessive friction and other forms of microtrauma can cause various dermatoses as well as lesions of hair and nails. This paper illustrates that microtraumata significantly influence many skin disorders, including those of occupational origin. PMID- 2933956 TI - Down syndrome owing to simple trisomy 21 in three first cousins. PMID- 2933957 TI - Surveillance of twin pregnancy with umbilical arterial velocimetry. AB - A continuous-wave Doppler system and a spectrum analyzer provide the tools for the measurement of systolic-diastolic velocity wave ratios in the umbilical arteries. In twins, each umbilical cord can be studied without imaging the fetuses. Results were tabulated by taking the average difference in the ratios between each fetus and plotting these values against the neonatal weight differences. In 43 twin pregnancies, the data revealed that ratio differences between fetuses that averaged 0.4 or more was predictive of a weight difference of greater than 349 gm. The sensitivity was 73% and specificity 82%. Two cases of twin transfusion syndrome were recognized by the simultaneous presence of high- and low-resistance values. PMID- 2933955 TI - Long-term experience in percutaneous transluminal dilatation of renal artery stenosis. AB - Percutaneous transluminal dilatation was attempted in 65 patients with renovascular hypertension. In five cases (8 percent), percutaneous transluminal dilatation could not be performed for technical reasons. In the remaining 60 patients (35 with atherosclerotic stenosis and 25 with fibromuscular dysplasia), both mean systolic and diastolic pressure fell immediately after percutaneous transluminal dilatation and remained significantly lower for a period of up to five years. Cure rates after a mean control period of 21.6 months were higher in patients with fibromuscular dysplasia (50 percent) than in those with atherosclerotic stenosis (29 percent). Improvement of blood pressure was observed in 32 percent of patients with fibromuscular dysplasia and in 48 percent of patients with atherosclerotic stenosis. Follow-up angiography in 33 cases showed occlusion of the dilated artery in two patients and recurrence of slight renal artery stenosis in nine patients. Successful redilatation could be performed in five of these cases. Furthermore, renal vein renin determinations were only of limited diagnostic or prognostic value. These results document the good long-term effect of percutaneous transluminal dilatation in patients with renal artery stenosis. Percutaneous transluminal dilatation should, therefore, be the favored procedure in patients with renovascular hypertension. PMID- 2933958 TI - Prenatal ultrasonic diagnosis of cloacal exstrophy. AB - Cloacal exstrophy is a rare malformation, but most of its prominent structural features can be observed by detailed ultrasonography. Reported is a case in which the anomaly was diagnosed on prenatal scanning. PMID- 2933959 TI - Systemic sclerosis and pregnancy complicated by obstructive uropathy. AB - A patient with progressive systemic sclerosis whose twin pregnancy was complicated by obstructive uropathy due, in part, to a noncompliant abdominal wall is reported. The effects of progressive systemic sclerosis on pregnancy and those of pregnancy on progressive systemic sclerosis are reviewed and discussed. PMID- 2933961 TI - A parental perspective on stress and coping. PMID- 2933960 TI - Monoclonal antibody phenotyping of B-cell non-Hodgkin's lymphomas. The Southeastern Cancer Study Group experience. AB - This report describes the experience of the Southeastern Cancer Study Group (SECSG) with the frozen-section immunoperoxidase phenotyping of 162 cases of B lineage non-Hodgkin's lymphomas. The authors used a panel of 13 different markers with varying degrees of specificity for B lymphocytes and B-cell neoplasms. All lymphomas were classified according to the International Working Formulation. Several antibodies, including anti-immunoglobulin, B1, Leu 12, and Leu 14 were B cell-specific markers that were generally pan-reactive. Several other monoclonal antibodies, however, were selectively reactive with subpopulations of B-cell lymphomas. Three "selective-B" antigens (BA1, p24, CALLA) were found on about half of the B-cell lymphomas tested, while another three (HB31, transferrin receptor, C3d receptor) were found on about two-thirds of the lymphomas tested. Leu 1 reacted with 18% of the B-cell lymphomas, particularly the small lymphocytic lymphomas. When the reactivity of the monoclonal antibodies was compared with the histologic classification, two important points became apparent. First, with the large panel of antibodies, there was tremendous phenotypic diversity even among histologically similar tumors. Second, however, not all possible combinations of antibody phenotypes were encountered. That is, clusters of antigenic phenotypes were seen, and these phenotypes correlated to some degree with the histologic diagnosis of the tumor. Small lymphocytic and follicular lymphomas tended to be phenotypically distinct, although there was some overlap. Intermediate- and high-grade lymphomas were phenotypically more diverse. The more common phenotypes of lymphomas encountered could not be reconciled with any simple linear scheme of neoplastic B-cell differentiation. PMID- 2933962 TI - Transport of N1-methylnicotinamide across brush border membrane vesicles from rabbit kidney. AB - A preparation of isolated brush border membranes from the rabbit renal cortex was used to examine the characteristics of N1-methylnicotinamide (NMN) transport in the kidney. Transport was independent of the presence of Na+ under Na+ equilibrium conditions. However, outwardly directed Na+ gradients stimulated NMN uptake, whereas inwardly directed Na+ gradients inhibited NMN uptake. Transport appeared to involve two parallel processes: one saturable with a Jmax of 5 nmol X mg protein-1 X min-1 and an apparent Kt of 0.6 mM, and a second that behaved like passive diffusion. Countertransport of NMN was observed when vesicles were preloaded with either NMN or another organic cation, tetraethylammonium (TEA). TEA and several structural analogues, as well as a wide variety of other organic cations and bases, were effective inhibitors of NMN uptake, though nicotinamide and p-aminohippuric acid did not interact with the uptake process. Outwardly directed proton gradients (pH 6.0 in, 7.6 out) stimulated transport, suggesting that NMN uptake may involve a countertransport of H+. The electrical potential difference across the vesicle membrane was manipulated using gradients of the permeant organic ion thiocyanate (SCN-); an outwardly directed gradient of SCN- (i.e., a depolarizing condition) stimulated uptake and produced a transient accumulation of NMN above that noted at equilibrium, whereas an inwardly directed SCN- gradient inhibited uptake of NMN. The data can be explained by postulating the presence of an electrogenic NMN+-H+ antiporter in the rabbit luminal membrane that could play a role in organic cation secretion. PMID- 2933963 TI - Atriopeptin II lowers cardiac output in conscious sheep. AB - Atrial natriuretic peptides cause natriuresis, kaliuresis, diuresis, and hypotension. They relax vascular smooth muscle in vitro, and they dilate renal vessels in vivo. Hence, we tested the hypothesis that they produce hypotension by lowering total peripheral resistance. The studies were performed in conscious chronically instrumented sheep standing quietly in their cages. Atriopeptin II (AP II) was infused into the right atrium for 30 min at 0.1 nmol X kg-1 X min-1. Atriopeptin II lowers arterial pressure (9%, P less than 0.05) by lowering cardiac output (18%, P less than 0.05), stroke volume (28%, P less than 0.05), and right atrial pressure (2.3 mmHg, P less than 0.05). Heart rate and total peripheral resistance increase (16 and 13%, respectively, P less than 0.05). Partial ganglionic blockade with trimethaphan camsylate during AP II infusion prevents the increases in heart rate and total peripheral resistance. The changes in right atrial pressure, stroke volume, and cardiac output persist, and arterial pressure falls further (27%, P less than 0.05). These hemodynamic data are consistent with direct AP II-induced relaxation of venous smooth muscle with reduction of venous return, right atrial pressure, stroke volume, cardiac output, and arterial pressure, followed by reflex activation of the sympathetic nervous system to increase heart rate and total peripheral resistance. Because partial ganglionic blockade alone and AP II alone cause similar reductions in right atrial pressure (2.1 and 2.3 mmHg, respectively) but AP II causes a greater fall in stroke volume (28 vs. 13%), it is possible that AP II also causes coronary vasoconstriction. PMID- 2933964 TI - Mechanism of action of vasoconstrictor responses to atriopeptin II in conscious SHR. AB - Previous studies have demonstrated that infusion of synthetic atriopeptin II (AP II) lowered arterial pressure, reduced regional blood flow, and increased total peripheral and regional vascular resistances in conscious spontaneously hypertensive rats (SHR). This study was designed to examine the mechanism(s) involved in regional vasoconstrictor responses to AP II. In these experiments, hemodynamic actions of AP II were examined in control, 6-hydroxydopamine-treated (chemically sympathectomized), and renal-denervated groups of instrumented conscious SHR. Infusion of AP II (1 microgram X kg-1 X min-1) caused similar reductions in mean arterial pressure in control (-22 +/- 2 mmHg), chemically sympathectomized (-23 +/- 2 mmHg), and renal-denervated (-23 +/- 3 mmHg) SHR. In control SHR, AP II infusion reduced renal (-20 +/- 3%), mesenteric (-26 +/- 2%), and hindquarters (-18 +/- 10%) blood flow and increased regional vascular resistance in all three beds. Chemical sympathectomy prevented the fall in renal blood flow (RBF) and significantly abolished the regional vasoconstrictor responses to AP II infusion. In unilateral renal-denervated groups of SHR, AP II reduced renal vascular resistance (RVR) -11 +/- 3% but failed to alter RBF (-3 +/ 1%) in denervated kidneys. In contrast, RVR increased (20 +/- 7%) and RBF was significantly reduced (-29 +/- 3%) in contralateral-innervated kidneys. This study demonstrated that chemical or surgical destruction of renal sympathetic nerves abolished AP II-induced increases in RVR. These data further indicate that in conscious SHR the regional vasoconstrictor responses to AP II infusion appear to be mediated by increases in sympathetic tone rather than through direct vascular actions of AP II. PMID- 2933965 TI - Compensation for occupational disease with multiple causes: the case of coal miners' respiratory diseases. AB - Many diseases associated with occupational exposures are clinically indistinguishable from diseases with non-occupational causes. Given this, how are fair decisions made about eligibility for compensation? This problem is discussed in relation to the federal black lung program. Conflicting definitions of terms- coal workers' pneumoconiosis as defined by the medical profession, pneumoconiosis as defined by the United States Congress, and the popular term, black lung--are important considerations in this discussion. Each is embedded in different logical interpretations of the causes of occupational disease and of disability. Alternative views are presented and critically discussed. PMID- 2933966 TI - Human cord blood suppressor T lymphocytes: I. Phenotype and target of the inducer of suppressor cell factor. AB - The present study examines the characteristics of the cord suppressor T cells and their targets. When an inducer of suppressor T cell factor (TisF) from culture supernatant of alloantigen-activated cord lymphocytes was used as a source of suppression, adult lymphocyte response to soluble antigen candidin, alloantigens, and pokeweed mitogen were all suppressed. These results suggest that TisF acts primarily on T cells in an antigen-nonspecific fashion. Furthermore, preculture T cell irradiation, but not T8+ cell depletion, of adult lymphocytes abrogated the suppressive effect of TisF on the PWM-stimulated IgG production, suggesting that the target of TisF belongs to the radiosensitive T8-(T4+) T cell subset. When different cord T cell subsets were tested for suppressor activity, only radiosensitive T4+ cells were capable of suppressing IgG production by adult lymphocytes. Neither preculture T8+ cell depletion nor irradiation of adult T cells affected the suppression. Taken together, these results suggest that the suppressor activity of cord T cells originated from an inducer of suppressor cells that activates radiosensitive T4+ suppressor effector cells through TisF. In turn, these effector cells act on either radioresistant T4+ helper T cells or B cells or both. PMID- 2933967 TI - Mantle-zone lymphoma. A pattern produced by lymphomas of more than one cell type. AB - We analyzed the distribution and immunologic phenotype of the neoplastic cells in eight cases of mantle-zone lymphoma. Although in all the cases the follicle centers appeared reactive on routine histologic examination, polyclonal staining for immunoglobulin was found in the follicle centers in only five of the eight cases; in the other three cases the follicle centers were monoclonal. In three cases, the immunologic phenotype was that of centrocytic (diffuse small cleaved cell) lymphoma: IgM+IgD+B1+B2+Ia+Tl+. In one case the phenotype was that of a follicular (centroblastic/centrocytic) lymphoma: IgG+B1+B2+Ia+CALLA+. In the other four cases, the phenotype was IgM+B1+B2+ or B2-Ia+; this phenotype can be seen in diverse B cell lymphomas. The phenotype of normal mantle-zone cells (IgM+IgD+B1+B2+Ia+) was not reproduced by any of the lymphomas. A mantle-zone pattern may be produced by either follicular or diffuse lymphomas of predominantly small cleaved cell type, and does not indicate an origin from the cells of the normal mantle zone. PMID- 2933968 TI - Acute cholecystitis associated with hepatic arterial infusion of floxuridine. AB - In a 1 year period, 13 patients underwent pump implantation for liver metastasis from a primary colorectal tumor. The gallbladders were not removed at the time of pump implantation in the initial six patients. In these patients, chemotherapy consisted of floxuridine given every 2 weeks followed by a 2 week rest period and cisplatin over 1 hour by way of the side portal on day 8 of the cycle. The treatment was repeated every 28 days. All patients whose gallbladders were not removed at the time of pump implantation required reoperation for acute or chronic acalculous cholecystitis from 1 to 9 months (mean 5.4 months) after pump implantation. At operation, all patients were found to have various degrees of inflammation and fibrosis. In one patient, significant sclerosing cholangitis was documented that involved the entire intrahepatic ductal system and hepatic duct bifurcation. Cholecystectomy and operative cholangiography are recommended in all patients who undergo pump implantation for metastatic disease to the liver. PMID- 2933969 TI - Eversion endarterectomy of the superficial femoral artery and end-to-side anastomosis to the deep femoral artery. An alternative to extended profundoplasty. AB - The success of aortofemoral reconstruction in patients with superficial femoral artery occlusion depends on the restoration of a satisfactory pulsatile flow to the deep femoral artery. In 18 patients with multilevel disease, widespread involvement of the deep femoral artery, and poor distal outflow, we performed an eversion endarterectomy of the proximal segment of the superficial femoral artery and constructed an end-to-side anastomosis between this segment and the distal deep femoral artery. In 10 patients, the reconstruction was performed after thrombectomy of the occluded aortofemoral graft, and in 8 the two reconstructions were simultaneous. The actuarial patency rate was 93.5 percent at 1 year and 75.2 percent at 5 years. Four late femorodistal bypasses were performed that gave an actuarial limb salvage rate of 68.8 percent at 1 year and 61.6 percent at 5 years. In selected cases, this technique is a valid alternative to an extended profundoplasty or to a femorodistal bypass. PMID- 2933970 TI - [Changes in bone structure of the skull and sella turcica in women in the climacteric period]. PMID- 2933971 TI - [Clinical aspects, diagnosis and treatment of endometrial polyps in the post menopausal period]. PMID- 2933972 TI - [Internal uterine endometriosis and characteristics of the climacteric in women]. PMID- 2933973 TI - [Effectiveness of treatment of patients with pre-menopausal dysfunctional uterine hemorrhages with norcolut]. PMID- 2933974 TI - [Prognosis of the development of primary infertility in relation to characteristics of the period of sexual maturation]. PMID- 2933975 TI - [Clinical and hormonal characteristics of patients with postpartum obesity]. PMID- 2933977 TI - [Anatomical and functional state of the ovaries in the climacteric period]. PMID- 2933976 TI - [Basal levels and diurnal rhythm of plasma concentrations of sex steroids and cortisol in women with Itsenko-Cushing syndrome at various stages of treatment]. PMID- 2933978 TI - [A method of complex examination of women with tubal infertility]. PMID- 2933979 TI - [Contractile activity the of fallopian tubes in infertile women after tubal pregnancy]. PMID- 2933981 TI - [Microsurgery in the treatment of patients with tubal infertility]. PMID- 2933980 TI - [Microsurgical reconstructive operations in tubo-peritoneal infertility]. PMID- 2933982 TI - [Artificial insemination with donor sperm in infertile marriages]. PMID- 2933984 TI - [Intrauterine contraceptive device as a risk factor of genital inflammatory process]. PMID- 2933983 TI - [Lipid metabolism in hormonal contraception]. PMID- 2933986 TI - [A method of monitoring ovulation and the luteal phase of the menstrual cycle]. PMID- 2933987 TI - [Current characteristics of the climacteric in women]. PMID- 2933985 TI - [Histochemical study of glycogen in the endometrium of women using intrauterine contraceptive devices]. PMID- 2933988 TI - [State of the hypothalamo-hypophyseo-ovarian function in patients with hyperandrogenemia during treatment with spironolactone]. PMID- 2933989 TI - [Improving the diagnosis of pathological processes in the endometrium]. PMID- 2933990 TI - [Pathogenesis of uremic hypogonadism and its treatment with parlodel]. PMID- 2933991 TI - [Roentgenologic diagnosis of endometriosis of the fallopian tubes in infertility]. PMID- 2933992 TI - [The causes of infertile marriages]. PMID- 2933994 TI - [Indications and individual contraindications for sanatorium-health resort treatment of gynecologic diseases]. PMID- 2933993 TI - [Diagnostic significance of various endocrine shifts in missed abortion]. PMID- 2933995 TI - [Current clinical characteristics and the principles of treatment of tuberculosis of female genital organs]. PMID- 2933996 TI - [Atypical form of the climacteric syndrome (climacteric myocardial dystrophy)]. PMID- 2933997 TI - Spurious blood cell counts and red cell indices from the Ortho ELT-8, associated with a cold-reactive antibody. PMID- 2933998 TI - Procaterol and terbutaline in bronchial asthma. A double-blind, placebo controlled, cross-over study. AB - Procaterol, a new beta-2 adrenoceptor stimulant, was studied in a double-blind, placebo-controlled, cross-over trial in patients with bronchial asthma. Oral procaterol 50 micrograms b.d., procaterol 100 micrograms b.d., and terbutaline 5 mg t.i.d., were compared when given randomly in 1-week treatment periods. The best clinical effect was found with terbutaline. Both anti-asthmatic and tremorgenic effects of procaterol were dose-related. Procaterol appeared effective in the doses tested, and a twice daily regimen would appear to be suitable with this drug. PMID- 2933999 TI - [Hemodynamic effects of an etomidate-flunitrazepam or midazolam- fentanyl combination for induction of anesthesia in patients with heart valve diseases]. AB - A comparison of the haemodynamic effects of 3 anaesthetic techniques, the combinations etomidate + fentanyl (I), flunitrazepam + fentanyl (II) or midazolam + fentanyl (III), respectively was carried out in 45 patients undergoing various types of cardiac valve replacement surgery. Haemodynamics were assessed by continuously measuring the heart rate as well as the blood pressure in the systemic and pulmonary circulations whereas the cardiac output was measured intermittently. In the first 30 minutes after induction of anaesthesia, a mean arterial blood pressure drop of 10% (I), 20% (II) or 15% (III) respectively, was observed; at the same time, the rate did not change significantly. Cardiac index, however, fell significantly in all 3 groups by 33% (I) 30% (II) or 28% (III), respectively. Pulmonary pressure, wedge pressure and systemic vascular resistance rose only in groups I and III and decreased in group II (flunitrazepam + fentanyl). On the other hand, pulmonary vascular resistance as well as left ventricular work index were significantly decreased in all 3 groups. We conclude that all 3 anaesthetic techniques investigated here may be effectively applied for safe induction of anaesthesia in patients with valvular lesions of the heart. On account of the effect of the combination flunitrazepam + fentanyl on decreasing pulmonary artery pressure and wedge pressure, this technique seems to be preferable in patients with pulmonary hypertension. PMID- 2934000 TI - Spinal anaesthesia for outpatient surgery. AB - In a prospective study of 51 young male outpatients given spinal anaesthesia through a 25-gauge needle, we found a 37.2% incidence of postdural puncture headache. In addition, 54.9% complained of backache after surgery. Occurrence of headache significantly prolonged the sick-leave from work. General anaesthesia would be preferred by 31.4% of patients for a similar procedure in the future. These patients had a higher incidence of postoperative backache and pain during lumbar puncture. It is concluded that spinal anaesthesia is not a satisfactory technique for outpatient procedures in young men. PMID- 2934001 TI - Diazepam mixed micelle--comparison with diazepam in propylene glycol and midazolam. AB - A mixed micelle formulation of diazepam was compared with midazolam and diazepam in propylene glycol for evidence of venous intolerance following IV injection. The overall incidence of venous morbidity was 17% for diazepam mixed micelle, 26% for midazolam and 90% for diazepam in propylene glycol. Diazepam mixed micelle is suggested as a preferable alternative to the standard formulation. PMID- 2934002 TI - Platelet function in platelet concentrates and in whole blood. AB - Platelet function was studied in CPD whole blood stored at 4 degrees C for one and three days and in platelet concentrates stored at room temperature for the same periods of time. Comparisons were made of platelet shape, nucleotide content, beta-thromboglobulin (beta TG) liberated during storage, and platelet aggregation in response to ADP, collagen, sodium arachidonate and ristocetin. It was found that in whole blood the shape of the platelets was less discoid than in platelet concentrates. However, platelet aggregation in response to ADP, collagen, and sodium arachidonate was preserved better in whole blood than in platelet concentrates. Platelet nucleotides were the same in whole blood as in platelet concentrates, but the plasma levels of beta TG were less in whole blood. The results show that as judged by aggregation, beta TG release and nucleotide content, platelets from whole blood were at least as functional as those from platelet concentrates. However, platelets from whole blood had lost their discoid shape, which suggests that they would have a short survival in the circulation. PMID- 2934003 TI - Purification of synexin by pH step elution from chromatofocusing media in the absence of ampholytes. AB - Synexin can be purified to virtual homogeneity by a modification of the conventional chromatofocusing technique. Ampholytes are omitted from the procedure altogether and the protein is eluted by a specific pH step chosen on the basis of the pI of the protein. This modification of the conventional method eliminates the separation of ampholytes from the purified protein, an insurmountable problem in our case, and reduces the cost of purification profoundly. PMID- 2934004 TI - Localization of Mg++-dependent adenosine triphosphatase and alkaline phosphatase activities in the postimplantation mouse embryos in day 5 and 6. AB - Mg++-dependent adenosine triphosphatase (Mg-ATPase) and alkaline phosphatase (ALPase) activities were histo- and cytochemically investigated in postimplantation mouse embryos from day 5 to day 6. In day 5 postimplantation embryos, Mg-ATPase activity was detected in the embryonic ectoderm and weakly in the visceral endoderm. Weak ALPase activity was found in the embryonic ectoderm and visceral endoderm. Parietal endoderm, both in day 5 and in day 6 embryos, had very weak or no Mg-ATPase and ALPase activities. Mg-ATPase activity in day 6 embryos was found with the same localization as that in day 5 embryos. No ALPase activity was observed in their embryonic ectoderm. Extraembryonic ectodermal cell mass had the strongest Mg-ATPase activity in these stage embryos. These results suggest that the localization of both enzyme activities in postimplantation mouse embryos is closely related to the morphogenesis. As regards the proamniotic cavity formation, the fact that Mg-ATPase activity was still observed in the embryonic ectoderm in these stages suggests the involvement of active transport system on the production of nascent proamniotic cavity fluid. PMID- 2934005 TI - A three-dimensional reconstruction of high endothelial venules in the mouse lymph node: an enzyme-histochemical study. AB - A three-dimensional reconstruction of high endothelial venules (HE-venules) of an entire mouse lymph node is presented. The reconstruction has been made by means of the histochemical technique for alpha-naphthylacetate esterase. The course of the HE-venules is shown in coherence with lymphocytic aggregates (follicles and unit), which were concomitantly reconstructed. Carbonic anhydrase, glutamate-, and alpha-glycerophosphate dehydrogenase were found in the high endothelia, while calcium-stimulated NA+, K+ ATP-ase and the acetylcholinesterase were localized to the endothelia and/or to the perivascular sheath of the HE-venules and submarginal capillaries. PMID- 2934006 TI - Midazolam as an intravenous induction agent in the elderly: a clinical and pharmacokinetic study. AB - Midazolam, the first benzodiazepine derivative with water-soluble salts, was studied as an induction agent in general anesthesia for the elderly. In group 1 (n = 14), 5 or 10 mg oral diazepam was used as premedication, but in group 2 (n = 9), both oral (10 mg dixyrazin as a night-time sedative) and intramuscular (0.01 mg/kg atropine + 1 mg/kg meperidine) premedicants were used. Serum concentrations of benzodiazepines were determined using both gas-liquid chromatographic (unchanged midazolam) and radioreceptor assays (binding equivalents of benzodiazepines plus their active metabolites). In general, midazolam, 0.15 mg/kg, intravenously resulted in smooth induction of anesthesia, although the time required for induction was rather long and a sudden but transient decrease in blood pressure was found in a significant number of patients. The course of anesthesia was otherwise satisfactory. A marked amnesic effect was observed, especially when diazepam was used as premedication. The pharmacokinetic parameters based on gas-liquid chromatographic measurements were quite comparable with those in young, healthy persons published earlier. In both groups, the binding equivalents measured with radioreceptor assay (reflecting total benzodiazepine activity) were higher than the levels of unchanged midazolam determined with gas-liquid chromatography. The relatively low dose of 0.15 mg/kg of midazolam needed for anesthetic induction in the elderly indicates not pharmacokinetic, but pharmacodynamic, alterations in older patients. We conclude that midazolam is a new intravenous induction agent for use in the elderly, but careful titration of the dosage according to the response of the patient is required. Diazepam premedication prior to midazolam causes a marked anterograde amnesic effect. PMID- 2934007 TI - General anesthesia and fragile X syndrome: report of a case. AB - A case report of an 11-year-old Caucasian boy with the fragile X syndrome is presented. The fragile X syndrome is a form of X-linked mental retardation with a connective tissue component that involves mitral valve prolapse. Antibiotic prophylaxis, electrocardiographic abnormalities, and special anesthetic management considerations are elements of treating patients with fragile X syndrome. The patient received morphine sulfate and scopolamine as a preoperative premedication. Ketamine was also administered intramuscularly prior to induction to gaseous anesthetic. Pancuronium was used to facilitate nasotracheal intubation. A wandering atrial pacemaker and progressive hypocapnia, both of which were managed without complication, were the only problems encountered in the anesthetic procedure. PMID- 2934008 TI - Relief of dental surgery pain: a controlled 12-hour comparison of etodolac, aspirin, and placebo. AB - Single doses of the study drugs were evaluated for 12 hours by 201 out-patients reporting moderate or severe pain following oral surgery. The results of this double-blind study indicated that 50, 100, and 200 mg of etodolac as well as 650 mg of aspirin were significantly more effective than placebo. A dose-response relationship was found for the three doses of etodolac, which was significant for summed pain relief scores for up to 8 hours. In terms of total analgesic effect, etodolac 200 mg was significantly superior to placebo for 8 hours, while aspirin and the two lower doses of etodolac were similarly effective in the range of 3-6 hours postdrug. All doses showed a favorable onset of analgesia (1/2-1 hour). Etodolac 200 mg resulted in a duration of action which was approximately twice as long as aspirin's and also produced a peak pain relief which was significantly greater than the lower doses of etodolac and aspirin. All study medications were well tolerated with no reports of significant adverse side effects. No dose related effects were observed with etodolac PMID- 2934010 TI - [Aortic flow measurement by transesophageal Doppler effect]. AB - Continuous measurement of cardiac output by thermodilution is invasive, impractical and unpleasant for the patient. We propose to measure descending aortic blood flow with a specially designed intra-oesophageal Doppler echo probe. The apparatus is composed of two main parts. First an A scan system makes possible the measurement of the diameter of the vessel, second a continuous wave velocimeter is used to measure the spatial mean velocity of the blood. An output calculator determines the descending aortic blood flow. The oesophageal catheter contains three ultrasonic transducers at its tip mounted on an epoxy resin bracket produced by moulding. They are connected to a flexible hose placed inside a flexible polyvinyl sheath whose outer diameter is 6.8 mm and length is 50 cm. A cylindrical latex balloon is mounted on this sheath which is water inflated to minimum pressure, ensuring a good ultrasonic coupling between the transducers and the oesophageal wall. Connection between the probe and the apparatus is made by three coaxial cables. Three isolator-transformers are built into the connector cable to ensure a safe electrical circuit. After having bled the probe of any air, the balloon is deflated. The probe is gently introduced into the oesophagus by nasal or oral route until the transducers are situated between the 5th and 6th vertebra. The balloon is then inflated to minimum pressure with 10 ml of distilled water contained in a syringe. To find the aorta, the velocimeter is first used like a Doppler stethoscope. The probe is rotated into a position corresponding to the maximum level of Doppler signal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2934009 TI - Effect of ipratropium bromide on repeated methacholine challenges. AB - The purpose of this study was to trace the protective effect of ipratropium bromide (IB) during methacholine inhalation challenge (MIC) at the first and fourth hour after its administration. IB-inhaler contains 0.02 mg IB in each puff and it was used in the usual dosage of two puffs (0.04 mg). In 20 asthmatic patients, the dose of methacholine caused a drop in FEV1 of 20% (PD20-FEV1). It was concluded that IB protected patients significantly one hour after its administration and showed a significant bronchodilating effect in comparison to placebo. IB protected 19 of the 20 patients one hour after administration during MIC while placebo protected none. IB protected 13 of the 20 patients, after the second PD20-FEV1 with methacholine, four hours after its administration. PMID- 2934012 TI - Effects of swallowing on the pattern of continuous respiration in human adults. AB - Swallowing must interact with respiration so that a swallow causes minimal or no disturbance of continual respiration. In order to study the coordinate control of swallowing and respiration, we investigated the effects of spontaneous and water induced swallows on the pattern of ongoing respiration in 8 adult human subjects. Swallows were identified by submental electromyograms and visual observation of the characteristic laryngeal movements. Both spontaneous and water-induced swallows occurred during all phases of the respiratory cycle, but approximately 80% of swallows occurred during the expiratory phase. No essential difference between spontaneous and water-induced swallows in the effects of the swallowing on respiration was observed. A swallow coinciding with the expiratory phase prolonged the duration of the same expiration that had been interrupted, whereas a swallow coinciding with the inspiratory phase interrupted the inspiration immediately and was followed by a short expiratory duration. There was a positive correlation between the time from the onset of the expiration to the onset of the swallowing and the duration of the expiration interrupted by the swallowing, indicating that the later the onset of the swallowing takes place, the more is the expiration prolonged. The duration of respiratory cycle in the breaths immediately following the swallow was not affected by the swallow, but there was a considerable increase in the tidal volume of the postswallowing breaths. These results suggest that the changes in respiratory pattern induced by the act of swallowing may depend on some mechanism that regulates the coordination of respiration and swallowing. PMID- 2934011 TI - Airways reversibility after prednisolone therapy in chronic asthma is associated with alterations in leukocyte function. AB - In 6 patients with chronic asthma, we studied the effects of orally administered prednisolone on monocyte and neutrophil membrane receptor expression for IgG (Fc) and complement, neutrophil locomotion, and calcium ionophore-induced leukotriene C4 production by granulocytes. Prior to treatment, monocyte IgG (Fc) and complement receptor expression, but not neutrophil IgG (Fc) or complement receptor expression, were increased when patients were compared with nonasthmatic control subjects (p less than 0.01 and p less than 0.01, respectively). After a 7 day course of orally administered prednisolone (30 mg/day daily), the increases in peak expiratory flow rate were accompanied by significant decreases from baseline in the percent of monocyte IgG (Fc) (Day 3, p less than 0.001; Day 7, p less than 0.001), monocyte complement (Day 3, p less than 0.001; Day 7, p less than 0.001), and neutrophil complement rosettes (Day 3, p less than 0.02; Day 7, p less than 0.02), but not neutrophil IgG (Fc) rosettes. Neutrophil locomotion in vitro, in response to casein, from the asthmatics was enhanced when compared with cells from control subjects, and was significantly depressed following prednisolone. Each of the 6 subjects had a peripheral blood eosinopenia in response to prednisolone that corresponded to a decrease in the amount of immunoreactive LTC4 generated from granulocyte suspensions challenged with the calcium ionophore A23187. These findings suggest that prednisolone suppresses monocyte and neutrophil activation in chronic asthma and that this is accompanied by an improvement in lung function. PMID- 2934013 TI - Relationship of increased lung serotonin levels to endotoxin-induced pulmonary hypertension in sheep. Effect of a serotonin antagonist. AB - A persistent pulmonary artery hypertension, increased airways resistance, increased vascular permeability to protein, and hypoxia are characteristic of sepsis-induced ARDS in humans and are present in the late phase injury response seen in sheep after endotoxin. Our purpose was to determine the role of serotonin, 5-HT, in the steady-state pulmonary hypertension and decreased arterial oxygen tension seen beginning approximately 3 h after Escherichia coli endotoxin injury (2 micrograms/kg) in the adult sheep. Plasma 5-HT levels remained constant, whereas lung lymph values increased from a baseline of 60 +/- 40 to 180 +/- 70 and 270 +/- 90 ng/ml at 1-h and at 3- to 5-h periods, respectively, after endotoxin. Platelet count decreased significantly only at the 3-h time period. Ketanserin, a 5-HT antagonist, was infused (0.15 mg/kg/h) in 7 sheep during endotoxin injury. The degree of early pulmonary hypertension and hypoxia was not affected by ketanserin. Mean values for pulmonary artery pressure and arterial oxygen tension were 40 +/- 8 mmHg and 70 +/- 8 torr for endotoxin alone and 38 +/- 7 mmHg and 72 +/- 7 torr for the ketanserin group. Steady-state, protein-rich pulmonary perfusion was also not altered, being increased 3-fold in both groups. Pulmonary hypertension and hypoxia were significantly attenuated, however, at the 3- to 5-h period with ketanserin, compared with endotoxin alone, the pulmonary artery pressure decreasing from 29 +/- 5 to 22 +/- 4 mmHg and the PaO2 increasing from 75 +/- 4 to 83 +/- 5 torr.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2934014 TI - Respiratory muscle dysfunction after herpes zoster. AB - We report an unusual neurologic complication of herpes zoster. After thoracic herpes zoster, our patient complained of severe shortness of breath as a result of myoclonus of the abdominal muscles as documented by electromyography. The myoclonus resulted in repetitive interruption of expiratory air flow, resulting in shortness of breath and a staccato speech. This case demonstrates the need to evaluate the function of all the respiratory muscles in a patient complaining of dyspnea. PMID- 2934015 TI - Polyarthritis and neutropenia. PMID- 2934016 TI - Annual reproductive rhythms in mammals: mechanisms of light synchronization. AB - Animals restrict the time of birth of offspring to the most advantageous time of year, usually spring or summer. This is achieved by controlling the preceding period of fertility and, in some cases, by delaying implantation of the zygote. Seasonal changes in daylength, the principal, though not the only cue, regulate pulsatile release of hypothalamic releasing factors that in turn activates the pituitary-gonadal axis. The role of the neuroendocrine system is therefore to translate the photoperiodic stimulus into an endocrine signal (Figure 12). The measurement of day length is a function of the circadian system, environmental light being sampled on a 24-hour basis. Experimental manipulations of the photoperiodic response have revealed the existence of a rhythm of sensitivity to the presence of light that is entrained by the prevailing photoperiod. Light falling within the period of maximal sensitivity results in an LD type response. It is important to note that although different species measure day length in a similar manner, the gonadal response to a given photoperiod will vary between species depending upon the nature of their seasonal reproductive strategy. Photic information is conveyed from the retina to the pineal gland by way of the suprachiasmatic nuclei of the hypothalamus and the cervical sympathetic trunk. The central connections between these structures are poorly understood. The pineal is an essential mediator of the photoperiodic response. The effects of pinealectomy vary between species, but in all cases the responses to changes in day length are blocked. The gland is neither anti- nor progonadotrophic; it merely provides a signal. This signal is probably the nocturnal release of melatonin. Studies on in vivo melatonin production and the responses of photoperiodic species to timed administration of exogenous melatonin have suggested that the duration of nocturnal melatonin production by the pineal is read by the CNS as an indicator of the length of darkness. This model for PTM provides a physiological basis to the observed rhythm of sensitivity to light. This period of sensitivity is probably a parallel to the nocturnal rhythm of melatonin production. Light falling in this phase blocks melatonin production, truncates the pineal signal, and hence produces an LD response by the CNS. The site of the signal detector is not known, although the anterior hypothalamus may be involved. How the pineal signal triggers changes in the hypothalamic LHRH pulse generator is not known. The endogenous opioids, however, especially beta END may have a major role in exercising photoperiodic control over pituitary action. PMID- 2934017 TI - New methods for applying synthetic pyrethroids when planting conifer seedlings: symptoms and exposure relationships. PMID- 2934018 TI - Continuous subcutaneous pethidine for routine postoperative analgesia. AB - We consider that the present state of postoperative analgesia is unsatisfactory because drugs are given intermittently and usually only at the patients' request and with nurses' acquiescence. A procedure for routine continuous pethidine infusion, suitable for administration and control by the nursing staff is described. The results of a trial on patients after major surgery are summarised. We believe the procedure to be more efficient and effective than those presently in use. PMID- 2934019 TI - Cellular immunity in acne vulgaris during transfer factor treatment. AB - The effect of treatment with human dialyzable transfer factor was investigated on acne vulgaris patients in a double-blind study. About 1/3 of the patients improved clinically during the study period but there was no correlation between clinical improvement and transfer factor treatment. Prior to treatment parameters of cell-mediated immunity were significantly altered in the patients. These alterations normalized during the study in all patients irrespective of transfer factor treatment, possibly due to the immunostimulatory effect of repeated skin testing. The present results support previous findings that acne patients have slightly altered cell-mediated immunity, but the results further suggest that abnormalities are not significant in the pathogenesis of acne vulgaris. PMID- 2934020 TI - Absence of significant autosomal lesions in Huntington's disease. AB - Peripheral blood from six patients with Huntington's disease (HD) and six controls were cultured in three types of media known to produce fragile sites. A total of 3000 metaphases per group were scrutinized in a blind coded study. No significantly specific 'hot-spot' was found capable of differentiating between HD patients and controls. PMID- 2934021 TI - Comparison of ciprofloxacin with azlocillin plus tobramycin in the therapy of experimental Pseudomonas aeruginosa endocarditis. AB - The efficacy of ciprofloxacin (Bay o 9867), a promising new quinolone, was compared with the efficacy of azlocillin plus tobramycin in rabbits with experimentally induced Pseudomonas aeruginosa endocarditis. The MBCs of ciprofloxacin, azlocillin, and tobramycin against the test strain were 0.5, 8, and 4 micrograms/ml respectively. Ciprofloxacin at a concentration of 50 mg/kg or azlocillin at a concentration of 200 mg/kg in combination with tobramycin at a concentration of 5 mg/kg was administered intramuscularly at 8-h intervals for 4 days. Both regimens produced median peak serum bactericidal titers of 1:8. The concentrations of ciprofloxacin, azlocillin, and tobramycin in serum, 1.8 +/- 0.7, 154 +/- 48, and 9.1 +/- 2.4 micrograms/ml (mean +/- standard deviation), respectively, closely approximated concentrations found in humans after accepted dosages. At the end of treatment, the titers of P. aeruginosa were 3.0 +/- 1.6 log10 CFU/g of vegetation (mean +/- standard deviation) for recipients of ciprofloxacin and 3.2 +/- 1.3 log10 CFU/g of vegetation for recipients of azlocillin plus tobramycin. These values compared with control titers of 7.3 +/- 1.6 CFU/g. These data indicate that at the doses used, ciprofloxacin was as effective as azlocillin plus tobramycin in the treatment of P. aeruginosa endocarditis in rabbits. Since the latter drug combination has proven efficacy, ciprofloxacin deserves further evaluation in the therapy of systemic infections in animal models and in humans. PMID- 2934023 TI - [Intra-arterial infusion chemotherapy with anticancer agents for advanced breast cancer--effect and toxicity of mitomycin C and adriamycin]. AB - In 23 cases of primary advanced breast cancer, intra-arterial infusion chemotherapy of Adriamycin (ADR) and Mitomycin C (MMC), which were injected jointly or individually, was performed and its effects and side effects were studied. As for the clinical effects, the response rate (CR + PR) was 73.9% (17/23 cases) and the histological response rate (greater than grade IIb) was 82.6% (19/23 cases). ADR alone (100-150 mg) and MMC (28 mg) + ADR (42 mg) combined regimens were especially superior in both their clinical and histological effects. In metastatic lymph nodes, the histological response rate was 78.9% (15/19 cases). As for the side effects, in the cases treated with MMC, bone marrow suppression such as leukocytopenia and thrombocytopenia was remarkable and took a long time to recover. The above results suggested that the most effective regimen for primary advanced breast cancer using intra-arterial infusion chemotherapy is ADR alone, in single doses of 50 mg up to a total dose of 150-200 mg. Histological examination of the effective cases revealed that the central region of the tumor was more markedly recrotic than the periphery. It was suggested that the grade of the effects on tumor tissues is related to the mechanism of anticancer agents. PMID- 2934022 TI - Evaluation of the in vitro bactericidal action of ciprofloxacin on cells of Escherichia coli in the logarithmic and stationary phases of growth. AB - Cells of Escherichia coli Neumann and E. coli KL16 were suspended in phosphate buffered saline pH 7.4 and allowed to reach stationary growth conditions. Ciprofloxacin was added at different concentrations, and time-kill curves were constructed. It could be demonstrated that the number of viable cells was reduced quickly by several logs for E. coli Neumann, whereas a weak and slow killing effect was observed with E. coli KL16. When ciprofloxacin or norfloxacin was added to logarithmically growing cultures of E. coli Neumann or E. coli KL16, no principal differences in the killing rate for the two strains could be observed. Ciprofloxacin, however, was more bactericidal than norfloxacin. It was also demonstrated that the bactericidal action of ciprofloxacin on cells in the stationary growth phase was better at pH 7.4 than at pH 8.6. This dependence is different from that observed in MIC studies, in which the MIC were lower at pH 8.0 than at pH 7.2. It was also found that the bactericidal action of ciprofloxacin or norfloxacin on cells of E. coli Neumann in the stationary phase of growth could not be reduced by the addition of chloramphenicol, whereas under conditions of logarithmic growth the rapid killing effect of ciprofloxacin was reduced in the presence of chloramphenicol. PMID- 2934024 TI - [An immunological study on the effect of simultaneous intrahepatic injection of an immunomodulator (OK-432) and adriamycin--an experiment in rats]. AB - An immunological study of the effect of a simultaneous intrahepatic injection of adriamycin (ADM) and OK-432 (PIC) in seven-week-old S.D. rats was carried out. Three experimental groups included an ADM-PIC-0.5 group which was administered 0.5 mg/kg ADM and 0.5 KE/kg PIC, an ADM-PIC-1.0 group which was administered 1.0 mg/kg ADM and 1.0 KE/kg PIC and an ADM-PIC-2.0 group which was administered 2.0 mg/kg ADM and 2.0 KE/kg PIC. A control group was injected with normal saline. The numbers of T-cells, B-cells, helper T-cells and suppressor T-cells were counted before, 1 day after and 5 days after intrahepatic injection. The suppressor T cell count decreased (p less than 0.05) in the ADM-PIC-0.5 group and the T-cell count (p less than 0.05), B-cell count (p less than 0.05), helper T-cell count (p less than 0.01), suppressor T-cell (p less than 0.05) and the ratio of suppressor T-cells among lymphocytes were decreased in the ADM-PIC-1.0 group. Decreases in the T-cell count (p less than 0.01), B-cell count (p less than 0.05), helper T cell count (p less than 0.01), suppressor T-cell (p less than 0.01) and the ratio of suppressor T-cells among lymphocytes (p less than 0.01) were recognized in the ADM-PIC-2.0 group one day after injection. Five days after injection, the ratio of suppressor T-cells among lymphocytes (p less than 0.01) was decreased in the ADM-PIC-0.5 group, and suppressor T-cells (p less than 0.05) and the ratio of suppressor T-cells among lymphocytes were decreased in the ADM-PIC-1.0 group. In the ADM-PIC-2.0 group, suppressor T-cell count (p less than 0.01) and the ratio of suppressor T-cells among lymphocytes were decreased. The result suggested that a simultaneous intrahepatic injection with PIC could improve the immunosuppression produced by an intrahepatic injection of ADM. PMID- 2934025 TI - [Clinical trial of 5'-DFUR against various malignant tumors]. AB - 5'-DFUR was administered orally to 18 patients with various malignant tumors at a daily dose of 800-1200 mg to evaluate its clinical efficacy and side effects. Out of 17 evaluable cases, PR was observed in one larynx cancer case and three breast cancer cases, with an efficacy rate of 23.5%. Side effects was observed in only one case. These were digestive symptoms which were alleviated by reduction of the dosage. No other severe side effect was observed. These results suggest that 5' DFUR has potential as a useful oral anticancer agent. PMID- 2934026 TI - [Clinical trial of 5'-deoxy-5-fluorouridine (5'-DFUR) in advanced cancer patients]. AB - 5'-DFUR was administered orally to advanced or recurrent cancer patients at a daily dosage of 600-1200 mg divided into 3 or 4 times a day. Out of 13 evaluable cases 2PR, 2MR, 4NC and 5PD were observed, response rate was 15.4%. PR were obtained in one gastric cancer case and one breast cancer case. Side effects were observed in 6 cases out of 14 cases (42.9%) and major adverse reaction was gastro intestinal toxicities such as anorexia, nausea-vomiting and diarrhea. Two leukocytopenia and one erythrocytopenia were observed. This study indicated that 5'-DFUR would be useful as a new anticancer agent. PMID- 2934027 TI - Treatment for renovascular hypertension. PMID- 2934029 TI - [Silent myocardial ischemia]. PMID- 2934028 TI - [Current status of gynecologic hormone therapy. Hyperandrogen disorders]. PMID- 2934030 TI - [Superior axial deviation in the young adult. An electro-vectorcardiographic study]. AB - We analyzed the VCGs of 100 young subjects without apparent cardiac disease showing an ECG superior Axis Deviation, i.e. AQRS greater than - 30 degrees, and a rS aspect in V1. Our findings demonstrated that, in these subjects, the superior axis deviation is due to a distal right bundle branch block with posterior displacement of the terminal forces in 78% of the cases. The other cases being left anterior hemiblocks, either isolated (12%) or associated with a block of the anterior subdivision of the right bundle branch (10%). The differential diagnosis, easy on VCG, is sometimes very difficult on ECG. The most reliable ECG criteria to discriminate this kind of right bundle branch block from left anterior hemiblock are: intrinsic deflection in a VL-V6 greater than or equal to 0.015" (sensitivity 100%; specificity 57%), RV6/Ra VL ratio greater than 1 (sensibility 100%; specificity 50%) and the presence of a notched R wave in L2, L3 and a VF (sensitivity 90%; specificity 100%). PMID- 2934031 TI - [Pseudonormalization of repolarization during physical exercise and the hemodynamic findings]. AB - The meaning of normalization of abnormal T waves during exercise is still unclear, twenty patients with this electrocardiographic pattern during treadmill stress test were studied with coronary arteriography. They were classified in two groups: Group I: In which 3 patients had isolated "pseudonormalization" of the T wave, and Group II with "pseudonormalization" of the T wave plus a positive stress test or an old myocardial infarction. Results allowed us to conclude that this phenomenon per se is not a diagnostic clue of coronary injury; however when we observe it associated with a positive stress test or an old myocardial infarction it may be indicative of severe and multiple coronary vessel injury. PMID- 2934033 TI - [Procoagulant activity associated with mononuclear cells in active rheumatic fever]. AB - Acute rheumatic fever (ARF) is associated with disseminated inflammation and tissue lesions with heavy fibrin deposition, specially in heart valves and myocardium. The immune pathogenesis of ARF has been suspected, but not satisfactorily proven. An active cellular immune reaction generates cell activators (lymphokines) from T cells, which are able to induce a procoagulant activity (PCA) in mononuclear cells. We studied PCA in peripheral blood mononuclear cells isolated form ARF patients as well as normal controls. The PCA from ARF was 1.5 to 15 times higher than the PCA from controls. This activity was associated with the presence of C-reactive protein and other acute phase markers. The PCA from mononuclear cells in ARF may be one of the mechanisms responsible for fibrin deposition. PMID- 2934032 TI - [Comparison of the postmortem anatomical study and bidimensional echocardiography in myocardial infarction]. AB - We studied 10 patients between the ages of 30 and 69 years, all of whom had suffered myocardial infarction (MI) at least 6 months before they died. Two dimensional echocardiography (2-D E) and catheterism were done no more than 15 days before death. The location and extension of MI were compared to the segmentary mobility (SM), end diastolic wall thickness (EDWT) and percentage of systolic wall thickening (PSWT) determined by 2-D E, in the 15 segments of the left ventricular wall. We also compared 2-D E and coronariographic findings. There was a good correlation between the location (P less than 0.01) and extension (P less than 0.05) of the necrotic area dyssynergy, specially when the MI was transmural. The postmortem measurement of the wall thickness in each one of the segments had also good correlation with the EDWT as measured with 2-D E (r = 0.926). The EDWT was less in the necrotic segments (8.8 +/- 1.8 mm) than in non affected segments (14.1 +/- 1.9 mm) and this difference was significant (P less than 0.05). The wall was thinnest in segment affected by transmural necrosis. The PSWT was significantly less (P less than 0.01) in necrotic segments (12.1 +/- 3%) than in segments without necrosis (24.1 +/- 4.3%). The alteration of SM correlated with coronary obstructions greater than 75%, specially when it was associated with necrosis. The EDWT was less in necrotic segments with important coronary artery obstruction than in those without necrosis even though vascular narrowing was marked (P less than 0.01). The PSWT was also less in the areas with necrosis when coronary obstruction was severe as well as moderate (11.3 +/- 2.3%) than in segments with coronary obstruction but without necrosis (22.3 +/- 4.2%) and even less than that obtained in cases with neither coronary artery obstruction nor necrotic area (30.1 +/- 2.2%) and the difference is statistically significant (P less than 0.01). The segmentary measurement by 2-D E of the EDWT and the PSWT are useful for recognizing areas with necrosis and differentiating it from ischemic areas of left ventricle in coronary artery disease. PMID- 2934034 TI - [Incidence of innocuous thoracic murmurs in a sample of 12,009 students]. AB - We have studied a total of 12,009 school children (age range 6 to 14 years) in order to determine the incidence of thoracic innocent murmurs. 6,816 were male and 5,193 female. A initial clinical evaluation was carried out in the school and the second examination was performed in our hospital. Global incidence of innocent murmurs was 9.57% with a female/male ratio of 1.73. We divided the innocent murmurs according with Fishleder's method: mesocardial systolic murmur (62%), pulmonary systolic murmur (26%), protosystolic apical murmur (7%), "whooping" murmur (5%). Afterwards, children with murmurs were divided in two groups of age and anthropometric characteristics observing a significative increment in the incidence of mesocardial systolic murmur in children which ranged ages from 6 to 10 years (74%) and of the pulmonary systolic murmur in the group of 10 to 14 years (40%). PMID- 2934035 TI - [Use of blood oxygen partial pressure in the right atrium in the calculation of intrapulmonary shunt]. AB - In order to assess the usefulness of blood samples taken from the right atrium (RA) in the calculation of intrapulmonary shunt (Qs/Qt), we correlated the values of Qs/Qt obtained through RA sampling with those obtained form a simultaneous sample of blood from the pulmonary artery (PA). The study was done in six mongrel dogs (15 to 23 Kg) who were anesthetized and artificially ventilated. The Qs/Qt measurements were repeated at different levels of cardiac output (CO). Changes in CO were elicited by both mechanical (A-V fistula) and pharmacological (Hydralazine) means. Besides the Qs/Qt correlation we also correlated the oxygen hemoglobin saturation (Sat %) and oxygen tension (PvO2) values between the two sites of mixed venous sampling. The correlations of the different parameters between RA and PA samples we obtained were as follows: Qs/Qt r = 0.93 (p less than 0.001); Sat % r = 0.87 (p less than 0.001); and for PvO2 r = 0.91 (p less than 0.001). The significant correlations of these parameters were maintained independent of the CO level. We conclude that in our model a sample of blood obtained from the RA is useful for the calculation of Qs/Qt. PMID- 2934036 TI - [Diagnosis using bidimensional echocardiography in a free thrombus of the left atrium]. AB - Left atrial thrombosis in patients with rheumatic mitral valve disease is frequent. It is important to establish an early diagnosis particularly in those patients who had previous thromboembolic episodes. We describe the case of a sixty-year-old woman with pure mitral stenosis and free left atrial thrombus. We emphasize the sensitivity and specificity of bidimensional echocardiography in such conditions. PMID- 2934037 TI - [Helicoidal ventricular tachycardia caused by amitriptyline. Presentation of a case]. AB - We present a case of a psychiatric patient treated with Amitriptyline who developed Stokes-Adams attacks with EKG manifestations of prolonged Q-T and "torsade de pointes". PMID- 2934038 TI - Use of clinical findings in the diagnosis of urinary tract infection in women. AB - To develop a decision rule for predicting urinary culture results in patients suspected of having urinary tract infection, we used discriminant analysis to identify the optimum combination of clinical findings. Thirty variables identified in a pilot study were recorded from 248 patients in a second study. Five findings were independent predictors of positive urinary culture: history of urinary tract infection, back pain, microscopic pyuria, hematuria, and bacteriuria. An additive decision rule that assigned one point for each of the five variables was tested in a third group of 258 patients. These scores stratified patients into subsets with increasing likelihood of positive culture. Higher scores identified patients who can confidently be treated without documentation of bacteriuria. If the rule applies successfully to other populations, cost savings could result from identification of patients who do not require quantitative urinary culture to demonstrate significant bacteriuria. PMID- 2934039 TI - Lepromatous leprosy: study of some subpopulations of lymphocytes and their functional analysis. PMID- 2934040 TI - User-friendly communication board for nonverbal, severely physically disabled individuals. AB - The inability to communicate personal needs, feelings, and ideas is a frustrating barrier for nonverbal patients with severe physical disabilities. It hampers the physician-patient relationship and medical services. This problem has been diminished with the use of a new communication board for patients with brain stem involvement. The communication board display is comprised of 36 squares in a 6 X 6 matrix. The alphabet is arranged in this matrix according to the normal sequence, and each row begins with a vowel. Selection of a desired alphabet letter is done by naming the vowels vertically until the appropriate row is reached, then the individual consonants horizontally until the proper one is indicated by the patient. With this new arrangement, the patient, attendant, or staff can memorize and functionally use the new communication board in a few minutes. PMID- 2934041 TI - Teratogenesis and reproductive safety evaluation of the retinoid etretin (Ro 10 1670). AB - Reproduction and teratology studies were performed with etretin, the free acid analog of the retinoid etretinate. The lowest teratogenic dose of etretin in mice, rats and rabbits was 3, 15 and 0.6 mg/kg, respectively. In all three species, the lowest dose which was embryolethal, fetolethal or reduced the survivability of the pups during lactation was 2-3 times higher than the above doses. In rats, the lowest effective dose of etretin was 3 mg/kg in both the study for fertility and general reproductive performance and the peri- and postnatal study. The main adverse effect in these two experiments was a reduced survival of the F1-generation. PMID- 2934042 TI - [75th anniversary of the Leningrad Society of Pathologic Anatomists]. PMID- 2934043 TI - Aerodynamic characteristics of Blom-Singer low-pressure voice prostheses. AB - In vitro airflow resistance calculations were completed for 20 low-pressure voice prostheses (Blom-Singer). Total device resistances ranged from 63.51 to 105.91 cm H2O per liter per second (LPS), with an overall average resistance of 82.04 cm H2O/LPS. Resistance characteristics were compared with those of other commercially available devices. PMID- 2934044 TI - Dacron mesh tray and cancellous bone in reconstruction of mandibular defects. AB - We used a Dacron-urethane mesh tray filled with cancellous bone for mandibular reconstruction in 17 patients. Five patients with traumatic defects and two with benign tumors developed solid, functional mandibles. Among ten patients with squamous cell carcinoma, eight had successful reconstruction; one required a second procedure. Mandibles of two of three patients with osteoradionecrosis were successfully reconstructed, but only one of three primary reconstructions was initially successful. The Dacron-urethane mesh tray has the advantage of being stiff but malleable. It easily fits the defect, is radiolucent, and may be used either before or after radiotherapy. We recommend delayed reconstruction, adequate soft-tissue coverage, good immobilization of the mandible, no intraoral contamination, especially with osteoradionecrosis, and hyperbaric oxygen in patients who have been irradiated or have osteoradionecrosis. PMID- 2934045 TI - Platelet interactions with Dacron vascular grafts. A model of acute thrombosis in baboons. AB - We have developed a model of acute Dacron graft thrombosis in baboons in order to assess platelet alterations secondary to arterial thrombus formation. In this model, thrombus formation was initiated by Dacron vascular grafts inserted as extension segments into chronic arteriovenous Silastic shunts. Following platelet labeling with 111In-oxine, platelet deposition was measured for 1 hour following blood contact under arterial flow conditions using a scintillation camera. Graft platelet activity rapidly increased 40- to 50-fold, plateauing by 1 hour. All grafts produced equivalent reductions in circulating platelet count and blood 111In-platelet radioactivity, demonstrating that the labeled cells were functionally equivalent to the total platelet population. After graft placement, the remaining platelets survived normally. Acute platelet deposition was equivalent on grafts placed 1, 24, 48, and 72 hours following injection of the labeled cells, indicating that a variable delay between platelet labeling and graft imaging was without detectable consequence. Platelet destruction by the graft produced a tenfold increase in plasma levels of platelet factor 4 (PF4) and beta-thromboglobulin (beta TG) but did not modify either the alpha-granule (PF4, beta TG) or dense granule (ADP, ATP) contents of circulating platelets. PMID- 2934046 TI - Combined discography and metrizamide myelography in evaluation of confusing low back pain. PMID- 2934047 TI - Reduction of stress in the chewing mechanism. PMID- 2934048 TI - Efficiency in occlusal function. PMID- 2934049 TI - Our changing health. PMID- 2934050 TI - The importance of correct jaw relations in cervico-oro-facial orthopedia. PMID- 2934051 TI - Combined dental and E.N.T. approach to T.M.J. dysfunction. PMID- 2934052 TI - Optimum dental prevention with vitamin E. PMID- 2934053 TI - Preventing the gagging reflex. PMID- 2934054 TI - The effects of chronic ethanol treatment on oligomycin sensitive ATPase activity in the guinea pig heart. AB - In an effort to determine the effect of chronic ethanol ingestion on myocardial oligomycin sensitive ATPase, guinea pigs were fed 15% ethanol instead of drinking water for 34 weeks. Mg2+-ATPase activity of isolated mitochondria was determined in control and alcohol fed guinea pigs at 16, 20, 24 and 34 weeks. To prove a possible higher fragility of the mitochondria from alcohol fed animals, the ATPase activity was also determined in the supernatant after the isolation of mitochondria "100 000 g fraction". Mg2+-ATPase activity of the isolated mitochondria was time dependent reduced to 56% of the value obtained in the control animals. In the "100 000 g fraction" the ATPase activity, however, started to increase after 8 weeks and after 34 weeks it was about twice as high than in the control group. The findings of this study document a decrease in oligomycin sensitive ATPase activity and an increase in mitochondrial fragility after chronic ethanol ingestion. It supports in the thesis that chronic alcohol intake affects the activity of the intrinsic membrane enzymes by structural derangements of mitochondrial membrane. The changes may play a role in the development of alcoholic cardiomyopathy. PMID- 2934055 TI - Caldesmon is a Ca2+-regulatory component of native smooth-muscle thin filaments. AB - Thin-filament preparations from four smooth muscle types (gizzard, stomach, trachea, aorta) all activate myosin MgATPase activity, are regulated by Ca2+, and contain actin, tropomyosin and a 120000-140000-Mr protein in the molar proportions 1:1/7:1/26. The 120000-140000-Mr protein from all sources is a potent inhibitor of actomyosin ATPase activity. Peptide-mapping and immunological evidence is presented showing that it is identical with caldesmon. Quantitative immunological data suggest that caldesmon is a component of all the thin filaments and that the thin-filament-bound caldesmon accounts for all the caldesmon in intact tissue. The myosin light-chain kinase content of thin filament preparations was found to be negligible. We propose that caldesmon-based thin-filament Ca2+ regulation is a physiological mechanism in all smooth muscles. PMID- 2934056 TI - Effects of the calcium-channel agonist CGP 28392 on insulin secretion from isolated rat islets of Langerhans. AB - The rate of insulin secretion from isolated rat islets of Langerhans was affected by a number of dihydropyridine derivatives known to interact with voltage sensitive Ca2+ channels in excitable cells. The channel antagonists nifedipine and nitrendipine were potent inhibitors of glucose-induced insulin secretion in response to both 8 mM- and 20 mM-glucose, although they did not lower the basal secretion rate observed in the presence of 4 mM-glucose. The Ca2+-channel agonist, CGP 28392, also failed to alter the basal rate of insulin secretion. In the presence of 8 mM-glucose, however, 1 microM-CGP 28392 enhanced the insulin secretion rate to a value approximately double that with 8 mM-glucose alone. This effect was dose-dependent, with half the maximal response elicited by 0.1 microM CGP 28392, and full enhancement at 10 microM. The response was rapid in onset, with an increase in insulin secretion evident within 2 min of CGP 28392 infusion in perifused islets. Stimulation of insulin secretion by CGP 28392 was correlated with a rapid enhancement of glucose-stimulated 45Ca2+ uptake into islets cells, and with a transiently increased rate of 45Ca2+ efflux from pre-loaded islets. Stimulation of insulin secretion by CGP 28392 was abolished in the presence of noradrenaline, although under these conditions the rapid stimulation of 45Ca2+ influx induced by CGP 28392 was only partially inhibited. In contrast with these results, when islets were incubated in the presence of 20 mM-glucose, CGP 28392 caused a dose-dependent inhibition of insulin secretion. Half-maximal inhibition required approx. 0.2 microM-CGP 28392, with maximal effects observed at 10 microM. Under these conditions, however, the extent of insulin secretion was still only decreased by about 50%, to a value which was similar to that seen in the presence of 8 mM-glucose and CGP 28392. These results suggest that dihydropyridine derivatives can alter the activity of voltage-dependent Ca2+ channels in islet cells, and are consistent with the possibility that gating of these channels plays an important role in regulating the rate of insulin secretion after glucose stimulation. PMID- 2934058 TI - The effect of multivalent ions on the inactivation of bacteriophage phi X174 by lipopolysaccharide from Escherichia coli C. AB - The inactivation of bacteriophage phi X174 by lipopolysaccharide from Escherichia coli C is promoted by multivalent metal ions and by polyamines. The effect of the two types of cation is similar, and the concentration causing 50% inactivation varies inversely with the charge on the cation, although quadrivalent amines are less active than expected. The increase in activity as the charge rises suggests that electrostatic binding is overwhelmingly important. PMID- 2934057 TI - Inhibitory antibodies to plasmalemmal Ca2+-transporting ATPases. Their use in subcellular localization of (Ca2+ + Mg2+)-dependent ATPase activity in smooth muscle. AB - Antibodies directed against the purified calmodulin-binding (Ca2+ + Mg2+)-ATPase [(Ca2+ + Mg2+)-dependent ATPase] from pig erythrocytes and from smooth muscle of pig stomach (antral part) were raised in rabbits. Both the IgGs against the erythrocyte (Ca2+ + Mg2+)-ATPase and against the smooth-muscle (Ca2+ + Mg2+) ATPase inhibited the activity of the purified calmodulin-binding (Ca2+ + Mg2+) ATPase from smooth muscle. Up to 85% of the total (Ca2+ + Mg2+)-ATPase activity in a preparation of KCl-extracted smooth-muscle membranes was inhibited by these antibodies. The (Ca2+ + Mg2+)-ATPase activity and the Ca2+ uptake in a plasma membrane-enriched fraction from this smooth muscle were inhibited to the same extent, whereas in an endoplasmic-reticulum-enriched membrane fraction the (Ca2+ + Mg2+)-ATPase activity was inhibited by only 25% and no effect was observed on the oxalate-stimulated Ca2+ uptake. This supports the hypothesis that, in pig stomach smooth muscle, two separate types of Ca2+-transport ATPase exist: a calmodulin-binding ATPase located in the plasma membrane and a calmodulin independent one present in the endoplasmic reticulum. The antibodies did not affect the stimulation of the (Ca2+ + Mg2+)-ATPase activity by calmodulin. PMID- 2934059 TI - Molecular forms of immunoactive atrial natriuretic peptide released from cultured rat atrial myocytes. AB - Primary cultures of atrial myocytes were prepared from newborn rats and maintained for 8 days in complete serum-free medium. The culture content of immunoactive atrial natriuretic peptide (ANP) increased from 10 to 25 ng/culture during this time. The cells released immunoactive ANP at a rate of 2 to 3% of culture content per hour in a linear fashion for at least 6 hours. When analyzed by gel filtration the major immunoactive material released by and contained within the cells displayed a molecular weight of approximately 15,000 daltons. The medium and cellular ANP-related peptides were further shown to be indistinguishable by reversed-phase HPLC. When the 15,000 dalton material was incubated with rat serum it was converted to ANP-related material possessing a molecular weight of approximately 3,000 daltons. These results suggest that under basal conditions, atrial myocytes release a large molecular weight form of ANP that is converted in the circulation to a low molecular weight form of ANP, which has been previously identified in plasma. PMID- 2934060 TI - Atrial natriuretic factor inhibits vasopressin secretion from rat posterior pituitary. AB - The effects of synthetic atrial natriuretic factor (ANF) were studied in superfused rat posterior pituitary gland. ANF (10(-6)M, 10(-10)M) significantly inhibited basal as well as KC1 (50 mM) or angiotensin II-stimulated immunoreactive arginine vasopressin secretion. The magnitude of inhibition was greater at 10(-6)M than at 10(-10)M. ANF also decreased cAMP secretion and increased cGMP secretion from the posterior pituitary. These results suggest that ANF directly acts on the posterior pituitary to inhibit arginine vasopressin secretion and that this effect is, at least, partly mediated by the changes in cyclic nucleotide production. PMID- 2934061 TI - Effect of temperature on siderophore production by Candida albicans. AB - The purpose of this study was to examine the effect of elevated temperature on growth and siderophore production by Candida albicans. The results showed that an increase in incubation temperature from 37 degrees C to 41 degrees C produced a marked decrease in both the rate and quantity of siderophore production. Elevated temperature was unable to suppress growth of C. albicans in either a control culture medium or a deferrated culture medium. A significant suppression of growth compared to the controls was observed in the deferrated media at both 37 degrees C and 41 degrees C. However with time, the growth of cells in the deferrated media showed partial recovery which was followed by an increase in siderophore production. Thus, elevation of temperature to suppress growth and siderophore production by C. albicans appears to be an ineffective host defense mechanism. PMID- 2934062 TI - Structure of dog and rabbit precursors of atrial natriuretic polypeptides deduced from nucleotide sequence of cloned cDNA. AB - The structure of precursors of dog and rabbit atrial natriuretic polypeptides was determined by nucleotide sequence analysis of cloned cDNA of mRNA encoding the peptides. The dog and rabbit precursors are 149 and 153 residues long having 23- and 25-residue putative signal peptides at their N-termini respectively. The 28 residue peptide with identical sequence to that of human, which has potent natriuretic activity, is located at the C-terminus of the dog precursor. The 28 residue peptide of identical sequence to that of mouse/rat is located at C terminus of rabbit precursor followed by additional Arg-Arg sequence which is also found in rat/mouse precursors and is apparently removed during processing. PMID- 2934063 TI - Antisera to atrial natriuretic factor reduces urinary sodium excretion and increases plasma renin activity in rats. AB - Although the presence of atrial natriuretic factor in the blood has been demonstrated by radioimmunoassay, its biological activity and physiological significance has not been elucidated. Using specific antiserum against atrial natriuretic factor, we investigated the effect of passive immunization in rats. A significant reduction of urine output and urinary sodium excretion lasted for about 30 min after intravenous administration of antiserum. The effects were more pronounced in rats pretreated with deoxycorticosterone acetate and saline. Plasma renin activity was increased after the administration of antiserum. No significant effects on the urinary sodium excretion was observed following injection of normal rabbit serum. The results of this study provide evidence indicating that endogenous atrial natriuretic factor plays an important role in the regulation of urinary water and sodium excretion and plasma renin activity. PMID- 2934064 TI - Dependence of the fluorescence of fluorescein labelled (Ca2+, Mg2+)-ATPase upon the lipid to protein ratio in sarcoplasmic reticulum reconstituted systems. AB - Reconstituted sarcoplasmic reticulum (SR) vesicles have been prepared mixing fluorescein labelled SR, excess endogenous lipids and deoxycholate by a rapid dilution protocol and several freeze-thaw treatments. We have found that both the steady-state level and the polarization of fluorescein fluorescence of these reconstituted systems monotonically increase as a function of the lipid to protein ratio between 80 and 2000 (on a mole per mole basis). The magnitude of this increase is about 15%. Detergents, such as Triton X-100 and deoxycholate, when added to SR labelled vesicles below their critical micelle concentrations also induce similar changes in fluorescein fluorescence. We suggest that lipid dilution of protein in these reconstituted systems induce a decrease of the level of self-quenching by promoting dissociation of (Ca2+, Mg2+)-ATPase. PMID- 2934066 TI - Effects of phenothiazine drugs on the active Ca2+ transport by sarcoplasmic reticulum. AB - The effect of phenothiazines (trifluoperazine and chlorpromazine) on the activity of the sarcoplasmic reticulum Ca2+ pump was investigated. These drugs have a biphasic action on the ATPase activity. They inhibit the enzyme at high concentrations, but below 150 microM, they promote a significant stimulation of the ATP hydrolysis, which is accompanied by a slight increase of the Ca2+ transport. Leaking of the membrane occurs only at drug concentrations above 150 microM. The phenothiazine stimulatory effect was not found in the isolated enzyme whose activity was inhibited at all concentrations studied. These results indicate that low concentrations of phenothiazines uncouple the sarcoplasmic reticulum Ca2+ pump without disrupting the membrane and that the drug stimulatory effect on the ATPase is not due to a direct interaction with the enzyme. It is suggested that a coupling factor or a specific microenvironment surrounding the enzyme regulates the association between the Ca2+ transport and the ATP hydrolysis by sarcoplasmic reticulum of the skeletal muscle cell. PMID- 2934065 TI - Fatty acid-dependent ethanol metabolism. AB - Rates of ethanol oxidation by perfused livers from fasted female rats were decreased from 82 +/- 8 to 11 +/- 7 mumol/g/hr by 4-methylpyrazole, an inhibitor of alcohol dehydrogenase. The subsequent addition of fatty acids of various chain lengths in the presence of 4-methylpyrazole increased rates of ethanol uptake markedly. Palmitate (1 mM) increased rates of ethanol oxidation to 95 +/- 8 mumol/g/hr, while octanoate and oleate increased rates to 58 +/- 11 and 68 +/- 15 mumol/g/hr, respectively. Hexanoate, a short-chain fatty acid oxidized predominantly in the mitochondria, had no effect. Addition of oleate also increased the steady-state level of catalase-H2O2. Pretreatment of rats for 1.5 hours with 3-amino-1,2,4-triazole (1.0 g/kg), an inhibitor of catalase, prevented the ethanol-dependent decrease in the steady-state level of catalase-H2O2 completely. Under these conditions, aminotriazole decreased rates of ethanol oxidation by about 50% and blocked the stimulation of ethanol oxidation by fatty acids. Oleate decreased rates of aniline hydroxylation by about 50%, indicating that cytochrome P450 is not involved in the stimulation of ethanol uptake by fatty acids. Furthermore, oleate stimulated ethanol uptake in livers from ADH negative deermice indicating that fatty acids do not simply displace 4 methylpyrazole from alcohol dehydrogenase. It is concluded that the stimulation of ethanol oxidation by fatty acids is due to increased H2O2 supplied by the peroxisomal beta-oxidation of fatty acids for the catalase-H2O2 peroxidation pathway. PMID- 2934067 TI - Hypoxia-mediated nitro-heterocyclic drugs in the radio- and chemotherapy of cancer. An overview. PMID- 2934068 TI - Biochemistry of reduction of nitro heterocycles. AB - Misonidazole is a metabolically active drug. Its addition to cells causes an immediate alteration in cellular electron transfer pathways. Under aerobic conditions the metabolic alterations can result in futile cycling with electron transfer to oxygen and production of peroxide. Thiol levels are extremely important in protecting the cell against the peroxide formation and potentially hazardous conditions for hydroxyl radical production. Nevertheless such electron shunting out of cellular metabolism will result in alterations in pentose cycle, glycolysis and cellular capacity to reduce metabolites to essential intermediates needed in DNA metabolism (i.e. deoxyribonucleotides). Glutathione must be depleted to very low levels before toxic effects of misonidazole and other nitro compounds are manifested in cell death via peroxidative damage. Under hypoxic conditions misonidazole also diverts the pentose cycle via its own reduction; however, unlike the aerobic conditions, there are a number of reductive intermediates produced that react with non-protein thiols such as GSH as well as protein thiols. The reaction with protein thiols results in the inhibition of glycolysis and other as yet undetermined enzyme systems. The consequences of the hypoxic pretreatment of cells with nitro compounds are increased vulnerability to radiation and chemotherapeutic drugs such as L-PAM, cis-platinum and bleomycin. The role that altered enzyme activity has in the cellular response to misonidazole and chemotherapeutic agents remains to be determined. It is also clear that the GSH depleted state not only makes cells more vulnerable to oxidative stress but also to hypoxic intermediates produced by the reduction of misonidazole beyond the one electron stage. The relevancy of the present work to the proposed use of thiol depletion in vivo to enhance the radiation or chemotherapeutic response of tumor tissue lies with the following considerations. Apparently, spontaneous peroxidative damage to normal tissue such as liver can occur with GSH depletion to 10-20% of control and with other normal tissue when GSH reaches 50% of control. This situation can obviously become more critical if peroxide producing drugs are administered. The only advantage to such combined drug treatments would lie in the possibility that tumors vary in their catalase and peroxidase activity and consequently may be more vulnerable to oxidative stress (cf. review by Meister. Our tumor model, the A549 human lung carcinoma cell in vitro, appears to be an exception because it has catalase, peroxidase and a high content of GSH.(ABSTRACT TRUNCATED AT 400 WORDS)